DNA methylation in inflammatory genes among children with obstructive sleep apnea.

PubMed

Kim, Jinkwan; Bhattacharjee, Rakesh; Khalyfa, Abdelnaby; Kheirandish-Gozal, Leila; Capdevila, Oscar Sans; Wang, Yang; Gozal, David

2012-02-01

Pediatric obstructive sleep apnea (OSA) leads to multiple end-organ morbidities that are mediated by the cumulative burden of oxidative stress and inflammation. Because not all children with OSA exhibit increased systemic inflammation, genetic and environmental factors may be affecting patterns of DNA methylation in genes subserving inflammatory functions. DNA from matched children with OSA with and without high levels of high-sensitivity C-reactive protein (hsCRP) were assessed for DNA methylation levels of 24 inflammatory-related genes. Primer-based polymerase chain reaction assays in a case-control setting involving 47 OSA cases and 31 control subjects were conducted to confirm the findings; hsCRP and myeloid-related protein (MRP) 8/14 levels were also assayed. Forkhead box P3 (FOXP3) and interferon regulatory factor 1 (IRF1) showed higher methylation in six children with OSA and high hsCRP levels compared with matched children with OSA and low hsCRP levels (P < 0.05). In the case-control cohort, children with OSA and high CRP levels had higher log FOXP3 DNA methylation levels compared with children with OSA and low CRP levels and control subjects. IRF1 did not exhibit significant differences. FOXP3 DNA methylation levels correlated with hsCRP and MRP 8/14 levels and with apnea-hypopnea index (AHI), BMI z score, and apolipoprotein B levels. A stepwise multiple regression model showed that AHI was independently associated with FOXP3 DNA methylation levels (P < 0.03). The FOXP3 gene, which regulates expression of T regulatory lymphocytes, is more likely to display increased methylation among children with OSA who exhibit increased systemic inflammatory responses. Thus, epigenetic modifications may constitute an important determinant of inflammatory phenotype in OSA, and FOXP3 DNA methylation levels may provide a potential biomarker for end-organ vulnerability.

"Magnetic resonance imaging negative positron emission tomography positive" temporal lobe epilepsy: FDG-PET pattern differs from mesial temporal lobe epilepsy.

PubMed

Carne, R P; Cook, M J; MacGregor, L R; Kilpatrick, C J; Hicks, R J; O'Brien, T J

2007-01-01

Some patients with temporal lobe epilepsy (TLE) lack evidence of hippocampal sclerosis (HS) on MRI (HS-ve). We hypothesized that this group would have a different pattern of 2-deoxy-2-[F-18]fluoro-D-glucose (FDG)-positron emission tomography (PET) hypometabolism than typical mesial TLE/HS patients with evidence of hippocampal atrophy on magnetic resonance imaging (MRI) (HS+ve), with a lateral temporal neocortical rather than mesial focus. Thirty consecutive HS-ve patients and 30 age- and sex-matched HS+ve patients with well-lateralized EEG were identified. FDG-PET was performed on 28 HS-ve patients and 24 HS+ve patients. Both groups were compared using statistical parametric mapping (SPM), directly and with FDG-PET from 20 healthy controls. Both groups showed lateralized temporal hypometabolism compared to controls. In HS+ve, this was antero-infero-mesial (T = 17.13); in HS-ve the main clustering was inferolateral (T = 17.63). When directly compared, HS+ve had greater hypometabolism inmesial temporal/hippocampal regions (T = 4.86); HS-ve had greater inferolateral temporal hypometabolism (T = 4.18). These data support the hypothesis that focal hypometabolism involves primarily lateal neocortical rather than mesial temporal structures in 'MRI-negative PET-positive TLE.'

The Role of Heparanase and Sulfatases in the Modification of Heparan Sulfate Proteoglycans within the Tumor Microenvironment and Opportunities for Novel Cancer Therapeutics

PubMed Central

Hammond, Edward; Khurana, Ashwani; Shridhar, Viji; Dredge, Keith

2014-01-01

Heparan sulfate proteoglycans (HSPGs) are an integral and dynamic part of normal tissue architecture at the cell surface and within the extracellular matrix. The modification of HSPGs in the tumor microenvironment is known to result not just in structural but also functional consequences, which significantly impact cancer progression. As substrates for the key enzymes sulfatases and heparanase, the modification of HSPGs is typically characterized by the degradation of heparan sulfate (HS) chains/sulfation patterns via the endo-6-O-sulfatases (Sulf1 and Sulf2) or by heparanase, an endo-glycosidase that cleaves the HS polymers releasing smaller fragments from HSPG complexes. Numerous studies have demonstrated how these enzymes actively influence cancer cell proliferation, signaling, invasion, and metastasis. The activity or expression of these enzymes has been reported to be modified in a variety of cancers. Such observations are consistent with the degradation of normal architecture and basement membranes, which are typically compromised in metastatic disease. Moreover, recent studies elucidating the requirements for these proteins in tumor initiation and progression exemplify their importance in the development and progression of cancer. Thus, as the influence of the tumor microenvironment in cancer progression becomes more apparent, the focus on targeting enzymes that degrade HSPGs highlights one approach to maintain normal tissue architecture, inhibit tumor progression, and block metastasis. This review discusses the role of these enzymes in the context of the tumor microenvironment and their promise as therapeutic targets for the treatment of cancer. PMID:25105093

Modification of gellan gum films by halloysite: physicochemical evaluation and drug permeation properties.

PubMed

Sakloetsakun, Duangkamon; Pongjanyakul, Thaned

2017-03-01

The aim of this study was to determine the potential of gellan gum (GG) and halloysite (HS) dispersions at different mixing ratios and to investigate the potential of GG-HS dispersions in film formation. To this end, the dispersions and films were characterized. The dispersions formed films with large particles ranging from 3 to 4 μm in size, with a zeta potential of ∼-35 mV. The GG-HS films were fabricated using a solvent-casting technique, which generated films with a white opaque appearance and rough surface. The GG-HS films were formed via hydrogen bonding and electrostatic interactions at the inner cavity and outer surface, as confirmed by ATR-FTIR spectroscopy and X-ray diffractometry. The %water uptake and erosion of the GG-HS film decreased with increasing HS content, whereas both puncture strength and elongation were increased in the GG-HS ratios of 1:0.4 and 1:1.2. Moreover, addition of HS into the GG films could possibly decrease drug permeability coefficient when using higher HS ratio in acidic and neutral media. These results suggested that HS modifies the characteristics of the GG used to coat modified-release tablets.

Exploratory power of the harmony search algorithm: analysis and improvements for global numerical optimization.

PubMed

Das, Swagatam; Mukhopadhyay, Arpan; Roy, Anwit; Abraham, Ajith; Panigrahi, Bijaya K

2011-02-01

The theoretical analysis of evolutionary algorithms is believed to be very important for understanding their internal search mechanism and thus to develop more efficient algorithms. This paper presents a simple mathematical analysis of the explorative search behavior of a recently developed metaheuristic algorithm called harmony search (HS). HS is a derivative-free real parameter optimization algorithm, and it draws inspiration from the musical improvisation process of searching for a perfect state of harmony. This paper analyzes the evolution of the population-variance over successive generations in HS and thereby draws some important conclusions regarding the explorative power of HS. A simple but very useful modification to the classical HS has been proposed in light of the mathematical analysis undertaken here. A comparison with the most recently published variants of HS and four other state-of-the-art optimization algorithms over 15 unconstrained and five constrained benchmark functions reflects the efficiency of the modified HS in terms of final accuracy, convergence speed, and robustness.

Explaining how brain stimulation can evoke memories.

PubMed

Jacobs, Joshua; Lega, Bradley; Anderson, Christopher

2012-03-01

An unexplained phenomenon in neuroscience is the discovery that electrical stimulation in temporal neocortex can cause neurosurgical patients to spontaneously experience memory retrieval. Here we provide the first detailed examination of the neural basis of stimulation-induced memory retrieval by probing brain activity in a patient who reliably recalled memories of his high school (HS) after stimulation at a site in his left temporal lobe. After stimulation, this patient performed a customized memory task in which he was prompted to retrieve information from HS and non-HS topics. At the one site where stimulation evoked HS memories, remembering HS information caused a distinctive pattern of neural activity compared with retrieving non-HS information. Together, these findings suggest that the patient had a cluster of neurons in his temporal lobe that help represent the "high school-ness" of the current cognitive state. We believe that stimulation here evoked HS memories because it altered local neural activity in a way that partially mimicked the normal brain state for HS memories. More broadly, our findings suggest that brain stimulation can evoke memories by recreating neural patterns from normal cognition.

Hippocampal atrophy on MRI is predictive of histopathological patterns and surgical prognosis in mesial temporal lobe epilepsy with hippocampal sclerosis.

PubMed

Jardim, Anaclara Prada; Corso, Jeana Torres; Garcia, Maria Teresa Fernandes Castilho; Gaça, Larissa Botelho; Comper, Sandra Mara; Lancellotti, Carmen Lúcia Penteado; Centeno, Ricardo Silva; Carrete, Henrique; Cavalheiro, Esper Abrão; Scorza, Carla Alessandra; Yacubian, Elza Márcia Targas

2016-12-01

To correlate hippocampal volumes obtained from brain structural imaging with histopathological patterns of hippocampal sclerosis (HS), in order to predict surgical outcome. Patients with mesial temporal lobe epilepsy (MTLE) with HS were selected. Clinical data were assessed pre-operatively and surgical outcome in the first year post surgery. One block of mid hippocampal body was selected for HS classification according to ILAE criteria. NeuN-immunoreactive cell bodies were counted within hippocampal subfields, in four randomly visual fields, and cell densities were transformed into z-score values. FreeSurfer processing of 1.5T brain structural images was used for subcortical and cortical volumetric estimation of the ipsilateral hippocampus. Univariate analysis of variance and Pearson's correlation test were applied for statistical analyses. Sixty-two cases (31 female, 32 right HS) were included. ILAE type 1 HS was identified in 48 patients, type 2 in eight, type 3 in two, and four had no-HS. Better results regarding seizure control, i.e. ILAE 1, were achieved by patients with type 1 HS (58.3%). Patients with types 1 and 2 had smaller hippocampal volumes compared to those with no-HS (p<0.001 and p=0.004, respectively). Positive correlation was encountered between hippocampal volumes and CA1, CA3, CA4, and total estimated neuronal densities. CA2 was the only sector which did not correlate its neuronal density with hippocampal volume (p=0.390). This is the first study correlating hippocampal volume on MRI submitted to FreeSurfer processing with ILAE patterns of HS and neuronal loss within each hippocampal subfield, a fundamental finding to anticipate surgical prognosis for patients with drug-resistant MTLE and HS. Copyright © 2016 Elsevier B.V. All rights reserved.

Chemical modifications of Au/SiO2 template substrates for patterned biofunctional surfaces.

PubMed

Briand, Elisabeth; Humblot, Vincent; Landoulsi, Jessem; Petronis, Sarunas; Pradier, Claire-Marie; Kasemo, Bengt; Svedhem, Sofia

2011-01-18

The aim of this work was to create patterned surfaces for localized and specific biochemical recognition. For this purpose, we have developed a protocol for orthogonal and material-selective surface modifications of microfabricated patterned surfaces composed of SiO(2) areas (100 μm diameter) surrounded by Au. The SiO(2) spots were chemically modified by a sequence of reactions (silanization using an amine-terminated silane (APTES), followed by amine coupling of a biotin analogue and biospecific recognition) to achieve efficient immobilization of streptavidin in a functional form. The surrounding Au was rendered inert to protein adsorption by modification by HS(CH(2))(10)CONH(CH(2))(2)(OCH(2)CH(2))(7)OH (thiol-OEG). The surface modification protocol was developed by testing separately homogeneous SiO(2) and Au surfaces, to obtain the two following results: (i) SiO(2) surfaces which allowed the grafting of streptavidin, and subsequent immobilization of biotinylated antibodies, and (ii) Au surfaces showing almost no affinity for the same streptavidin and antibody solutions. The surface interactions were monitored by quartz crystal microbalance with dissipation monitoring (QCM-D), and chemical analyses were performed by polarization modulation-reflexion absorption infrared spectroscopy (PM-RAIRS) and X-ray photoelectron spectroscopy (XPS) to assess the validity of the initial orthogonal assembly of APTES and thiol-OEG. Eventually, microscopy imaging of the modified Au/SiO(2) patterned substrates validated the specific binding of streptavidin on the SiO(2)/APTES areas, as well as the subsequent binding of biotinylated anti-rIgG and further detection of fluorescent rIgG on the functionalized SiO(2) areas. These results demonstrate a successful protocol for the preparation of patterned biofunctional surfaces, based on microfabricated Au/SiO(2) templates and supported by careful surface analysis. The strong immobilization of the biomolecules resulting from the described protocol is advantageous in particular for micropatterned substrates for cell-surface interactions.

Role of heparan sulfate in sexually transmitted infections

PubMed Central

Tiwari, Vaibhav; Maus, Erika; Sigar, Ira M; Ramsey, Kyle H; Shukla, Deepak

2012-01-01

Cell surface heparan sulfate (HS), a polysaccharide composed of alternating uronic acid and glucosamine residues, represents a common link that many sexually transmitted infections (STIs) require for infection. Variable modifications within the monomeric units of HS chains together with their unique structural conformations generate heterogeneity, which expands the ability of HS to bind a diverse array of host and microbial proteins. Recent advances made in the field of glycobiology have critically enhanced our understanding of HS and its interactions with microbes and their significance in important human diseases. The role of HS has been elaborated for several STIs to include those caused by herpes simplex virus, human immunodeficiency virus, human papillomavirus, and Chlamydia. In addition, gonorrhea, syphilis, and yeast infections are also dependent on the presence of HS on human target cells. Critical steps such as pathogen adhesion or binding to host cells followed by internalization to enhance intracellular survival and possible spread to other cells are mediated by HS. In addition, HS guided cell signaling plays a role in the development of angiogenesis and inflammation associated with many STIs. Past and ongoing investigations are providing new push for the development of HS-mimetics and analogs as novel prevention strategies against many different STIs. This review article summarizes the significance of HS in STIs and describes how emerging new products that target HS can be used to control the spread of STIs. PMID:22773448

Heat shock during early somitogenesis induces caudal vertebral column defects in Atlantic salmon (Salmo salar).

PubMed

Wargelius, Anna; Fjelldal, Per Gunnar; Hansen, Tom

2005-07-01

In several terrestrial vertebrates, heat shock (HS) during somitogenesis causes vertebral deformities. To determine if vertebral deformities can occur due to sudden temperature changes during early development in fish, Atlantic salmon embryos were HS treated during somitogenesis. Ten months later these individuals displayed a high prevalence of caudal vertebral column condensations (27-34%). The defects were located caudally of the abdominal cavity, displaying an even distribution in this region independent of time of HS. To determine if HS disturbed vertebral development during somitogenesis, two genes coding for markers of skeletal development were identified, namely, the secreted protein Shh (Sashh) and the transcription factor Twist (Satwist). These proteins are involved in the proliferation and specification of presumptive skeletal cells (sclerotome) in vertebrates. The spatial expression pattern of sashh and satwist in salmon indicated a functional conservation of these proteins. Furthermore, HS embryos displayed expressional disturbance in both sashh and satwist, indicating an effect of HS on sclerotomal cell patterning. However, the HS-protecting ability in embryos seems to be individually regulated because reduction in gene expression was not detected at all stages; in addition, HS did not induce somitic disturbance and vertebral deformity in all embryos.

There's no place like home: an analysis of migration patterns of dermatology residents prior to, during, and after their training.

PubMed

Chen, Allison J; Schwartz, Julia; Kimball, Alexandra B

2016-06-15

Previous studies have established migration patterns between the geographic location of physicians' residency programs and their first post-training job. Our study explores the patterns of migration of pre-residency education locations with residency and post-residency geography. We analyzed responses to an annual survey administered between 2008 and 2013 to participants of the board examination review courses organized by Galderma Laboratories. Geography of high school (HS), medical school (MS), residency, and first job location were highly correlated. The Midwest and South retained the most residents from HS (70% each), whereas the West retained the lowest percent of residents from HS (33%). The West and Northeast exported about half of their HS graduates to the South and MW for residency. The South retained the largest proportion of its trainees post-residency (75%). Our data revealed that both HS and MS locations are closely related to residents' ultimate employment locations. This information may be useful to training program directors and chairpersons as they manage recruitment and retention of trainees and faculty and may inform plans to address geographic workforce imbalances.

Characterization of Foot-Strike Patterns: Lack of an Association With Injuries or Performance in Soldiers.

PubMed

Warr, Bradley J; Fellin, Rebecca E; Sauer, Shane G; Goss, Donald L; Frykman, Peter N; Seay, Joseph F

2015-07-01

Characterize the distribution of foot-strike (FS) patterns in U.S. Army Soldiers and determine if FS patterns are related to self-reported running injuries and performance. 341 male Soldiers from a U.S. Army Combined Arms Battalion ran at their training pace for 100 meters, and FSs were recorded in the sagittal plane. Participants also completed a survey related to training habits, injury history, and run times. Two researchers classified FS patterns as heel strike (HS) or nonheel strike (NHS, combination of midfoot strike and forefoot strike patterns). Two clinicians classified the musculoskeletal injuries as acute or overuse. The relationship of FS type with two-mile run time and running-related injury was analyzed (p ≤ 0.05). The Soldiers predominately landed with an HS (87%) and only 13% were characterized as NHS. Running-related injury was similar between HS (50.3%) and NHS (55.6%) patterns (p = 0.51). There was no difference (p = 0.14) between overuse injury rates between an HS pattern (31.8%) and an NHS pattern (31.0%). Two-mile run times were also similar, with both groups averaging 14:48 minutes. Soldiers were mostly heel strikers (87%) in this U.S. Army Combined Arms Battalion. Neither FS pattern was advantageous for increased performance or decreased incidence of running-related injury. Reprint & Copyright © 2015 Association of Military Surgeons of the U.S.

Effect of patient sex on white matter alterations in unilateral medial temporal lobe epilepsy with hippocampal sclerosis assessed by diffusion tensor imaging.

PubMed

Oguz, K K; Tezer, I; Sanverdi, E; Has, A C; Bilginer, B; Dolgun, A; Saygi, S

2013-05-01

Studies shows ictal behavior and symptoms are affected by patient sex in temporal lobe epilepsy. The purpose of our study was to determine whether alterations in the WM as assessed by DTI display different patterns in male and female patients with unilateral HS. Patients with unilateral HS were categorized as women with right HS (n=12), men with right HS (n=10), women with left HS (n=12), and men with left HS (n=10). DTI of the brain along 64 noncollinear directions was obtained from 44 patients and 37 sex-matched control participants. We used TBSS to analyze whole-brain WM. Regions with significant changes of FA and MD, and their mean FA, MD, total number of significant voxels, and asymmetry indices were determined for each group. All groups showed bilateral and extensive reductions of FA and elevated MD in the WM, more prominent ipsilateral to the affected hippocampus. The total number of voxels with decreased FA in patients compared with that of control participants was higher in women with right HS (24,727 vs 5,459) and in men with left HS (27,332 vs 14,013) than in their counterparts. Changes in MD associated with right HS were more extensive in both men and women (right vs left HS, women: 16,926 vs 5,458; men: 5,389 vs 4,764) than in those with left HS. In patients with right HS, the ipsilateral cingulum, uncinate fasciculus, internal and external capsules, and right acoustic radiation were involved extensively in women. Women and men showed different patterns in extent of WM alterations associated with HS.

Multi-Targeted Molecular Effects of Hibiscus sabdariffa Polyphenols: An Opportunity for a Global Approach to Obesity

PubMed Central

Herranz-López, María; Olivares-Vicente, Mariló; Barrajón-Catalán, Enrique; Segura-Carretero, Antonio; Joven, Jorge; Micol, Vicente

2017-01-01

Improper diet can alter gene expression by breaking the energy balance equation and changing metabolic and oxidative stress biomarkers, which can result in the development of obesity-related metabolic disorders. The pleiotropic effects of dietary plant polyphenols are capable of counteracting by modulating different key molecular targets at the cell, as well as through epigenetic modifications. Hibiscus sabdariffa (HS)-derived polyphenols are known to ameliorate various obesity-related conditions. Recent evidence leads to propose the complex nature of the underlying mechanism of action. This multi-targeted mechanism includes the regulation of energy metabolism, oxidative stress and inflammatory pathways, transcription factors, hormones and peptides, digestive enzymes, as well as epigenetic modifications. This article reviews the accumulated evidence on the multiple anti-obesity effects of HS polyphenols in cell and animal models, as well as in humans, and its putative molecular targets. In silico studies reveal the capacity of several HS polyphenols to act as putative ligands for different digestive and metabolic enzymes, which may also deserve further attention. Therefore, a global approach including integrated and networked omics techniques, virtual screening and epigenetic analysis is necessary to fully understand the molecular mechanisms of HS polyphenols and metabolites involved, as well as their possible implications in the design of safe and effective polyphenolic formulations for obesity. PMID:28825642

Proteomic identification of erythrocyte membrane protein deficiency in hereditary spherocytosis.

PubMed

Peker, Selen; Akar, Nejat; Demiralp, Duygu Ozel

2012-03-01

Hereditary spherocytosis (HS) is the most common congenital hemolytic anemia in Caucasians, with an estimated prevalence ranging from 1:2000 to 1:5000. The molecular defect in one of the erythrocytes (RBC) membrane proteins underlying HS like; spectrin-α, spectrin-β, ankyrin, band 3 and protein 4.2 that lead to membrane destabilization and vesiculation, may change the RBCs into denser and more rigid cells (spherocytes), which are removed by the spleen, leading to the development of hemolytic anemia. It is classified as mild, moderate and severe, according to the degree of the hemolytic anemia and the associated symptoms. Two-dimensional gel electrophoresis (2-DE) is potentially valuable method for studying heritable disorders as HS that involve membrane proteins. This separation technique of proteins based upon two biophysically unrelated parameters; molecular weight and charge, is a good option in clinical proteomics in terms of ability to separate complex mixtures, display post-translational modifications and changes after phosphorylation. In this study, we have used contemporary methods with some modifications for the solubilisation, separation and identification of erythrocyte membrane proteins in normal and in HS RBCs. Spectrin alpha and beta chain, ankyrin and band 3 proteins expression differences were found with PDQuest software 8.0.1. and peptide mass fingerprinting (PMF) analysis performed for identification of proteins in this study.

Multi-Targeted Molecular Effects of Hibiscus sabdariffa Polyphenols: An Opportunity for a Global Approach to Obesity.

PubMed

Herranz-López, María; Olivares-Vicente, Mariló; Encinar, José Antonio; Barrajón-Catalán, Enrique; Segura-Carretero, Antonio; Joven, Jorge; Micol, Vicente

2017-08-20

Improper diet can alter gene expression by breaking the energy balance equation and changing metabolic and oxidative stress biomarkers, which can result in the development of obesity-related metabolic disorders. The pleiotropic effects of dietary plant polyphenols are capable of counteracting by modulating different key molecular targets at the cell, as well as through epigenetic modifications. Hibiscus sabdariffa (HS)-derived polyphenols are known to ameliorate various obesity-related conditions. Recent evidence leads to propose the complex nature of the underlying mechanism of action. This multi-targeted mechanism includes the regulation of energy metabolism, oxidative stress and inflammatory pathways, transcription factors, hormones and peptides, digestive enzymes, as well as epigenetic modifications. This article reviews the accumulated evidence on the multiple anti-obesity effects of HS polyphenols in cell and animal models, as well as in humans, and its putative molecular targets. In silico studies reveal the capacity of several HS polyphenols to act as putative ligands for different digestive and metabolic enzymes, which may also deserve further attention. Therefore, a global approach including integrated and networked omics techniques, virtual screening and epigenetic analysis is necessary to fully understand the molecular mechanisms of HS polyphenols and metabolites involved, as well as their possible implications in the design of safe and effective polyphenolic formulations for obesity.

Surgical pathology of epilepsy-associated non-neoplastic cerebral lesions: a brief introduction with special reference to hippocampal sclerosis and focal cortical dysplasia

PubMed Central

Miyata, Hajime; Hori, Tomokatsu; Vinters, Harry V.

2014-01-01

Among epilepsy-associated non-neoplastic lesions, mesial temporal lobe epilepsy with hippocampal sclerosis (mTLE-HS) and malformation of cortical development (MCD) including focal cortical dysplasia (FCD), are the two most frequent causes of drug-resistant focal epilepsies constituting about 50% of all surgical pathology of epilepsy. Several distinct histological patterns have been historically recognized in both HS and FCD, and several studies have tried to perform clinicopathological correlation; results, however, have been controversial, particularly in terms of postsurgical seizure outcome. Recently, the International League Against Epilepsy constituted a Task Forces of Neuropathology and FCD within the Commission on Diagnostic Methods, to establish an international consensus of histological classification of HS and FCD, respectively, based on agreement with the recognition of the importance of defining a histopathological classification system that reliably has some clinicopathological correlation. Such consensus classifications are likely to facilitate future clinicopathological study. Meanwhile, we reviewed neuropathology of 41 surgical cases of mTLE, and confirmed three type/patterns of HS along with no HS, based on the qualitative evaluation of the distribution and severity of neuronal loss and gliosis within hippocampal formation; i.e., HS type 1 (61%) equivalent to ‘classical’ Ammon’s horn sclerosis, HS type 2 (2%) representing CA1 sclerosis, HS type 3 (17%) equivalent to end folium sclerosis, and no HS (19%). Furthermore we performed a neuropathological comparative study on mTLE-HS and dementia associated HS (d-HS) in elderly, and confirmed that neuropathological features differ between mTLE-HS and d-HS in the distribution of hippocampal neuronal loss and gliosis, morphology of reactive astrocytes and their protein expression, and presence of concomitant neurodegenerative changes particularly Alzheimer type and TDP-43 pathologies. These differences may account, at least in part, for the difference in pathogenesis and epileptogenicity of HS in mTLE and senile dementia. However, the etiology and pathogenesis of most epileptogenic lesions are yet to be elucidated. PMID:23530853

Macrophage polarization alters the expression and sulfation pattern of glycosaminoglycans.

PubMed

Martinez, Pierre; Denys, Agnès; Delos, Maxime; Sikora, Anne-Sophie; Carpentier, Mathieu; Julien, Sylvain; Pestel, Joël; Allain, Fabrice

2015-05-01

Macrophages are major cells of inflammatory process and take part in a large number of physiological and pathological processes. According to tissue environment, they can polarize into pro-inflammatory (M1) or alternative (M2) cells. Although many evidences have hinted to a potential role of cell-surface glycosaminoglycans (GAGs) in the functions of macrophages, the effect of M1 or M2 polarization on the biosynthesis of these polysaccharides has not been investigated so far. GAGs are composed of repeat sulfated disaccharide units. Heparan (HS) and chondroitin/dermatan sulfates (CS/DS) are the major GAGs expressed at the cell membrane. They are involved in numerous biological processes, which rely on their ability to selectively interact with a large panel of proteins. More than 20 genes encoding sulfotransferases have been implicated in HS and CS/DS biosynthesis, and the functional repertoire of HS and CS/DS has been related to the expression of these isoenzymes. In this study, we analyzed the expression of sulfotransferases as a response to macrophage polarization. We found that M1 and M2 activation drastically modified the profiles of expression of numerous HS and CS/DS sulfotransferases. This was accompanied by the expression of GAGs with distinct structural features. We then demonstrated that GAGs of M2 macrophages were efficient to present fibroblast growth factor-2 in an assay of tumor cell proliferation, thus indicating that changes in GAG structure may contribute to the functions of polarized macrophages. Altogether, our findings suggest a regulatory mechanism in which fine modifications in GAG biosynthesis may participate to the plasticity of macrophage functions. © The Author 2014. Published by Oxford University Press. All rights reserved. For permissions, please e-mail: journals.permissions@oup.com.

Effects of exercise on c-reactive protein in healthy patients and in patients with heart disease: A meta-analysis.

PubMed

Hammonds, Tracy L; Gathright, Emily C; Goldstein, Carly M; Penn, Marc S; Hughes, Joel W

2016-01-01

Decreases in circulating hsCRP have been associated with increased physical activity and exercise training, although the ability of exercise interventions to reduce hsCRP and which individuals benefit the most remains unclear. This meta-analysis evaluates the ability of exercise to reduce hsCRP levels in healthy individuals and in individuals with heart disease. A systematic review and meta-analysis was conducted that included exercise interventions trials from 1995 to 2012. Forty-three studies were included in the final analysis for a total of 3575 participants. Exercise interventions significantly reduced hsCRP (standardized mean difference -0.53 mg/L; 95% CI, -0.74 to -0.33). Results of sub-analysis revealed no significant difference in reductions in hsCRP between healthy adults and those with heart disease (p = .20). Heterogeneity between studies could not be attributed to age, gender, intervention length, intervention type, or inclusion of diet modification. Exercise interventions reduced hsCRP levels in adults irrespective of the presence of heart disease.​. Copyright © 2016 Elsevier Inc. All rights reserved.

Obchs: AN Effective Harmony Search Algorithm with Oppositionbased Chaos-Enhanced Initialization for Solving Uncapacitated Facility Location Problems

NASA Astrophysics Data System (ADS)

Heidari, A. A.; Kazemizade, O.; Abbaspour, R. A.

2015-12-01

In this paper, a continuous harmony search (HS) approach is investigated for tackling the Uncapacitated Facility Location (UFL) task. This article proposes an efficient modified HS-based optimizer to improve the performance of HS on complex spatial tasks like UFL problems. For this aim, opposition-based learning (OBL) and chaotic patterns are utilized. The proposed technique is examined against several UFL benchmark challenges in specialized literature. Then, the modified HS is substantiated in detail and compared to the basic HS and some other methods. The results showed that new opposition-based chaotic HS (OBCHS) algorithm not only can exploit better solutions competently but it is able to outperform HS in solving UFL problems.

Ordered to isotropic morphology transition in pattern-directed dewetting of polymer thin films on substrates with different feature heights.

PubMed

Roy, Sudeshna; Mukherjee, Rabibrata

2012-10-24

Controlled dewetting of a thin polymer film on a topographically patterned substrate is an interesting approach for aligning isotropic dewetted structures. In this article, we investigate the influence of substrate feature height (H(S)) on the dewetting pathway and final pattern morphology by studying the dewetting of polystyrene (PS) thin films on grating substrates with identical periodicity (λ(P) = 1.5 μm), but H(S) varying between 10 nm and 120 nm. We identify four distinct categories of final dewetted morphology, with different extent of ordering: (1) array of aligned droplets (H(S) ≈ 120 nm); (2) aligned undulating ribbons (H(S) ≈ 70-100 nm); (3) multilength scale structures with coexisting large droplets uncorrelated to the substrate and smaller droplets/ribbons aligned along the stripes (H(S) ≈ 40-60 nm); and (4) large droplets completely uncorrelated to the substrate (H(S) < 25 nm). The distinct morphologies across the categories are attributed to two major factors: (a) whether the as-cast film is continuous (H(S)≤ 80 nm) or discontinuous (H(S)≥ 100 nm) and (b) in case of a continuous film, whether the film ruptures along each substrate stripe (H(S)≥ 70 nm) or with nucleation of random holes that are not correlated to the substrate features (H(S)≤ 60 nm). While the ranges of H(S) values indicated in the parentheses are valid for PS films with an equivalent thickness (h(E)) ≈ 50.3 nm on a flat substrate, a change in h(E) merely alters the cut-off values of H(S), as the final dewetted morphologies and transition across categories remain generically unaltered. We finally show that the structures obtained by dewetting on different H(S) substrates exhibits different levels of hydrophobicity because of combined spatial variation of chemical and topographic contrast along the surface. Thus, the work reported in this article can find potential application in fabricating surfaces with controlled wettability.

Extracellular dopamine, acetylcholine, and activation of dopamine D1 and D2 receptors after selective breeding for cocaine self-administration in rats.

PubMed

Xu, Haiyang; Das, Sasmita; Sturgill, Marc; Hodgkinson, Colin; Yuan, Qiaoping; Goldman, David; Grasing, Kenneth

2017-08-01

The low self-administration (LS)/Kgras (LS) and high self-administration (HS)/Kgras (HS) rat lines were generated by selective breeding for low- and high-intravenous cocaine self-administration, respectively, from a common outbred Wistar stock (Crl:WI). This trait has remained stable after 13 generations of breeding. The objective of the present study is to compare cocaine preference, neurotransmitter release, and dopamine receptor activation in LS and HS rats. Levels of dopamine, acetylcholine, and cocaine were measured in the nucleus accumbens (NA) shell of HS and LS rats by tandem mass spectrometry of microdialysates. Cocaine-induced locomotor activity and conditioned-place preference were compared between LS and HS rats. HS rats displayed greater conditioned-place preference scores compared to LS and reduced basal extracellular concentrations of dopamine and acetylcholine. However, patterns of neurotransmitter release did not differ between strains. Low-dose cocaine increased locomotor activity in LS rats, but not in HS animals, while high-dose cocaine augmented activity only in HS rats. Either dose of cocaine increased immunoreactivity for c-Fos in the NA shell of both strains, with greater elevations observed in HS rats. Activation identified by cells expressing both c-Fos and dopamine receptors was generally greater in the HS strain, with a similar pattern for both D1 and D2 dopamine receptors. Diminished levels of dopamine and acetylcholine in the NA shell, with enhanced cocaine-induced expression of D1 and D2 receptors, are associated with greater rewarding effects of cocaine in HS rats and an altered dose-effect relationship for cocaine-induced locomotor activity.

Tissue-Specific Methylation of Long Interspersed Nucleotide Element-1 of Homo Sapiens (L1Hs) During Human Embryogenesis and Roles in Neural Tube Defects.

PubMed

Wang, L; Chang, S; Guan, J; Shangguan, S; Lu, X; Wang, Z; Wu, L; Zou, J; Zhao, H; Bao, Y; Qiu, Z; Niu, B; Zhang, T

2015-01-01

Epigenetic regulation of long interspersed nucleotide element-1 (LINE-1) retrotransposition events plays crucial roles during early development. Previously we showed that LINE-1 hypomethylation in neuronal tissues is associated with pathogenesis of neural tube defect (NTD). Herein, we further evaluated LINE-1 Homo sapiens (L1Hs) methylation in tissues derived from three germ layers of stillborn NTD fetuses, to define patterns of tissue specific methylation and site-specific hypomethylation at CpG sites within an L1Hs promoter region. Stable, tissue-specific L1Hs methylation patterns throughout three germ layer lineages of the fetus, placenta, and maternal peripheral blood were observed. Samples from maternal peripheral blood exhibited the highest level of L1Hs methylation (64.95%) and that from placenta showed the lowest (26.82%). Between samples from NTDs and controls, decrease in L1Hs methylation was only significant in NTD-affected brain tissue at 7.35%, especially in females (8.98%). L1Hs hypomethylation in NTDs was also associated with a significant increase in expression level of an L1Hs-encoded transcript in females (r = -0.846, p = 0.004). This could be due to genomic DNA instability and alternation in chromatins accessibility resulted from abnormal L1Hs hypomethylation, as showed in this study with HCT-15 cells treated with methylation inhibitor 5-Aza.

Open-field temporal pattern of ambulation in Japanese quail genetically selected for contrasting adrenocortical responsiveness to brief manual restraint.

PubMed

Kembro, J M; Satterlee, D G; Schmidt, J B; Perillo, M A; Marin, R H

2008-11-01

Japanese quail selected for a low-stress (LS), rather than a high-stress (HS), plasma corticosterone response to brief restraint have been shown to possess lower fearfulness and a nonspecific reduction in stress responsiveness. Detrended fluctuation analysis provides information on the organization and complexity of temporal patterns of behavior. The present study evaluated the temporal pattern of ambulation of LS and HS quail in an open field that represented a novel environment. Time series of 4,200 data points were collected for each bird by registering the distance ambulated every 0.5 s during a 35-min test period. Consistent with their known reduced fearfulness, the LS quail initiated ambulation significantly sooner (P < 0.02) and tended to ambulate more (P < 0.09) than did their HS counterparts. Detrended fluctuation analyses showed a monofractal series (i.e., a series with similar complexity at different temporal scales) in 72% of the birds. These birds initiated their ambulatory activity in less than 600 s. Among these birds, a lower (P < 0.03) autosimilarity coefficient (alpha) was found in the LS quail than in their HS counterparts (alpha = 0.76 +/- 0.03 and 0.87 +/- 0.03, respectively), suggesting a more complex (less regular) ambulatory pattern in the LS quail. However, when the patterns of ambulation were reexamined by considering only the active period of the time series (i.e., after the birds had initiated their ambulatory activity), monofractal patterns were observed in 97% of the birds, and no differences were found between the lines. Collectively, the results suggest that during the active period of open-field testing, during which fear responses are likely less strong and other motivations are the driving forces of ambulation, the LS and HS lines have similar ambulatory organization.

Hidradenitis suppurativa: A practical review of possible medical treatments based on over 350 hidradenitis patients.

PubMed

Scheinfeld, Noah

2013-04-15

Hidradenitis suppurativa (HS), a pathological follicular disease, impacts patients' lives profoundly. HS most commonly involves cutaneous intertriginous areas, such as the axilla, inner thighs, groin and buttocks, and pendulous breasts, but can appear on any follicular skin. Protean, HS manifests with variations of abscesses, folliculitis, pyogenic granulomas, scars (oval honeycombed), comedones, tracts, fistulas, and keloids. The pathophysiology might involve both defects of the innate follicular immunity and overreaction to coagulase negative Staphylococcus. Treatment depends on the morphology, extent, severity, and duration. Topical clindamycin and dapsone are often adequate for treating mild HS. For Stage 1 and 2 HS, first line treatment combines rifampin with either oral clindamycin or minocycline. Other HS treatments include: fluoroquinolones with metronidazole and rifampin, oral dapsone, zinc, acitretin, hormone blockers (oral contraceptive pills, spironolactone, finasteride, and dutasteride), and oral prednisone. For severe HS, cyclosporine, adalimumab, or infliximab (used at double psoriatic doses) and intravenous carbapenems or cephalosporins are often required. Isotretinoin, etanercept, isoniazid, lymecycline, sulfasalazine, methotrexate, metformin, colchicine, clarithromycin, IVIG, and thalidomide are less favored treatments. The role of botulinum toxin is uncertain. The most important life style modification is weight loss. De-roofing fluctuant nodules and injection of intralesional corticosteroids ameliorates the disease and perhaps, if done at regular intervals, improves HS more permanently. Surgical excision and CO2 laser ablation are more definitive treatments. The 1064 nm laser for hair removal aids in the treatment of HS. This article centers on medical therapies and will only passingly mention surgical and laser treatments. This article summarizes my treatment experience with over 350 HS patients.

Hippocampal Sclerosis of Aging, a Common Alzheimer's Disease 'Mimic': Risk Genotypes are Associated with Brain Atrophy Outside the Temporal Lobe.

PubMed

Nho, Kwangsik; Saykin, Andrew J; Nelson, Peter T

2016-01-01

Hippocampal sclerosis of aging (HS-Aging) is a common brain disease in older adults with a clinical course that is similar to Alzheimer's disease. Four single-nucleotide polymorphisms (SNPs) have previously shown association with HS-Aging. The present study investigated structural brain changes associated with these SNPs using surface-based analysis. Participants from the Alzheimer's Disease Neuroimaging Initiative cohort (ADNI; n = 1,239), with both MRI scans and genotype data, were used to assess the association between brain atrophy and previously identified HS-Aging risk SNPs in the following genes: GRN, TMEM106B, ABCC9, and KCNMB2 (minor allele frequency for each is >30%). A fifth SNP (near the ABCC9 gene) was evaluated in post-hoc analysis. The GRN risk SNP (rs5848_T) was associated with a pattern of atrophy in the dorsomedial frontal lobes bilaterally, remarkable since GRN is a risk factor for frontotemporal dementia. The ABCC9 risk SNP (rs704180_A) was associated with multifocal atrophy whereas a SNP (rs7488080_A) nearby (∼50 kb upstream) ABCC9 was associated with atrophy in the right entorhinal cortex. Neither TMEM106B (rs1990622_T), KCNMB2 (rs9637454_A), nor any of the non-risk alleles were associated with brain atrophy. When all four previously identified HS-Aging risk SNPs were summed into a polygenic risk score, there was a pattern of associated multifocal brain atrophy in a predominately frontal pattern. We conclude that common SNPs previously linked to HS-Aging pathology were associated with a distinct pattern of anterior cortical atrophy. Genetic variation associated with HS-Aging pathology may represent a non-Alzheimer's disease contribution to atrophy outside of the hippocampus in older adults.

Hippocampal Sclerosis of Aging, a Common Alzheimer’s Disease ‘Mimic’: Risk Genotypes are Associated with Brain Atrophy Outside the Temporal Lobe

PubMed Central

Nho, Kwangsik; Saykin, Andrew J.; Nelson, Peter T.

2016-01-01

Hippocampal sclerosis of aging (HS-Aging) is a common brain disease in older adults with a clinical course that is similar to Alzheimer’s disease. Four single-nucleotide polymorphisms (SNPs) have previously shown association with HS-Aging. The present study investigated structural brain changes associated with these SNPs using surface-based analysis. Participants from the Alzheimer’s Disease Neuroimaging Initiative cohort (ADNI; n = 1,239), with both MRI scans and genotype data, were used to assess the association between brain atrophy and previously identified HS-Aging risk SNPs in the following genes: GRN, TMEM106B, ABCC9, and KCNMB2 (minor allele frequency for each is >30%). A fifth SNP (near the ABCC9 gene) was evaluated in post-hoc analysis. The GRN risk SNP (rs5848_T) was associated with a pattern of atrophy in the dorsomedial frontal lobes bilaterally, remarkable since GRN is a risk factor for frontotemporal dementia. The ABCC9 risk SNP (rs704180_A) was associated with multifocal atrophy whereas a SNP (rs7488080_A) nearby (~50 kb upstream) ABCC9 was associated with atrophy in the right entorhinal cortex. Neither TMEM106B (rs1990622_T), KCNMB2 (rs9637454_A), nor any of the non-risk alleles were associated with brain atrophy. When all four previously identified HS-Aging risk SNPs were summed into a polygenic risk score, there was a pattern of associated multifocal brain atrophy in a predominately frontal pattern. We conclude that common SNPs previously linked to HS-Aging pathology were associated with a distinct pattern of anterior cortical atrophy. Genetic variation associated with HS-Aging pathology may represent a non-Alzheimer’s disease contribution to atrophy outside of the hippocampus in older adults. PMID:27003218

Humic Substances: Determining Potential Molecular Regulatory Processes in Plants

PubMed Central

Shah, Zahid Hussain; Rehman, Hafiz M.; Akhtar, Tasneem; Alsamadany, Hameed; Hamooh, Bahget T.; Mujtaba, Tahir; Daur, Ihsanullah; Al Zahrani, Yahya; Alzahrani, Hind A. S.; Ali, Shawkat; Yang, Seung H.; Chung, Gyuhwa

2018-01-01

Humic substances (HSs) have considerable effects on soil fertility and crop productivity owing to their unique physiochemical and biochemical properties, and play a vital role in establishing biotic and abiotic interactions within the plant rhizosphere. A comprehensive understanding of the mode of action and tissue distribution of HS is, however, required, as this knowledge could be useful for devising advanced rhizospheric management practices. These substances trigger various molecular processes in plant cells, and can strengthen the plant’s tolerance to various kinds of abiotic stresses. HS manifest their effects in cells through genetic, post-transcriptional, and post-translational modifications of signaling entities that trigger different molecular, biochemical, and physiological processes. Understanding of such fundamental mechanisms will provide a better perspective for defining the cues and signaling crosstalk of HS that mediate various metabolic and hormonal networks operating in plant systems. Various regulatory activities and distribution strategies of HS have been discussed in this review. PMID:29593751

Damage-Associated Molecular Patterns (DAMPs) in Resuscitated Hemorrhagic Shock Are Mitigated by Peritoneal Fluid Administration.

PubMed

Matheson, Paul J; Eid, Mark A; Wilson, Matthew A; Graham, Victoria S; Matheson, Samuel A; Weaver, Jessica Lee; Downard, Cynthia D; Smith, Jason W

2018-05-03

Conventional resuscitation (CR) of hemorrhagic shock (HS), a significant cause of trauma mortality, is I.V. blood and fluids. CR restores central hemodynamics, but vital organ flow can drop causing hypoperfusion, hypoxia, Damage-Associated Molecular Patterns (DAMPs), and remote organ dysfunction (i.e., lung). CR plus Direct Peritoneal Resuscitation (DPR) prevents intestinal and hepatic hypoperfusion. We hypothesized that DPR prevents lung injury in HS/CR by altering DAMPs. Anesthetized male SD rats were randomized to groups (n=8/group) in one of two sets: 1) Sham (no HS, CR, or DPR); 2) HS/CR (HS=40% MAP for 60min, CR=shed blood + 2 volumes NS); or 3) HS/CR+DPR. First set underwent whole lung blood flow by colorimetric microspheres. Second set underwent tissue collection for Luminex, ELISAs, and histopathology. Lipopolysaccharide (LPS) and DAMPs were measured in serum and/or lung including cytokines, hyaluronic acid (HA), high mobility group box 1 (HMGB1), toll-like receptor 4 (TLR4), MYD88, and TRIF. Statistics were by ANOVA and Tukey-Kramer test with a priori P<0.05. HS/CR increased serum LPS, HA, HMGB1 and some cytokines (IL-1α, IL-1β, IL-6, and interferon-γ). Lung TLR4 and MYD88 were increased but not TRIF compared to Shams. HS/CR+DPR decreased LPS, HA, cytokines, HMGB1, TLR4, and MYD88 levels but did not alter TRIF compared to HS/CR. Data suggest that gut-derived DAMPs can be modulated by adjunctive DPR to prevent activation of lung TLR-4-mediated processes. Also, DPR improved lung blood flow and reduced lung tissue injury. Adjunctive DPR in HS/CR potentially improves morbidity/mortality by down-regulating the systemic DAMP response.

Effect of red yeast rice combined with antioxidants on lipid pattern, hs-CRP level, and endothelial function in moderately hypercholesterolemic subjects.

PubMed

Cicero, Arrigo F G; Morbini, Martino; Parini, Angelo; Urso, Riccardo; Rosticci, Martina; Grandi, Elisa; Borghi, Claudio

2016-01-01

Our aim was to test, through a crossover, double-blind, placebo-controlled randomized clinical trial, if a short-term treatment with 10 mg monacolins combined with antioxidants could improve lipid pattern, high-sensitivity C-reactive protein (hs-CRP), and endothelial function in a small cohort of moderately hypercholesterolemic subjects. Thus, 25 healthy, moderately hypercholesterolemic subjects were consecutively enrolled and, after 4 weeks of stabilization diet, were randomized to the sequence placebo followed by a washout, monacolins or monacolins followed by a washout, placebo, with each period being 4 weeks long. At each study step, a complete lipid pattern, safety parameters, hs-CRP, and endothelial function have been measured. When compared to the placebo phase, during monacolin treatment, patients experienced a more favorable percentage change in total cholesterol (TC) (TC after monacolin treatment, -18.35%; TC after placebo treatment, -5.39%), low-density lipoprotein cholesterol (LDL-C) (LDL after monacolin treatment, -22.36%; LDL after placebo treatment, -1.38%), non-high-density lipoprotein cholesterol (HDL-C) (non-HDL after monacolin treatment, -22.83%; non-HDL after placebo treatment: -7.15%), hs-CRP (hs-CRP after monacolin treatment: -2.33%; hs-CRP after placebo treatment, 2.11%), and endothelial function (pulse volume displacement after monacolin treatment, 18.59%; pulse volume displacement after placebo treatment, -6.69%). No significant difference was observed with regard to triglycerides, HDL-cholesterol, and safety parameters. On the basis of our data, we could demonstrate that a 10 mg monacolin nutraceutical treatment appears to safely reduce cholesterolemia, hs-CRP, and markers of vascular remodeling in moderately hypercholesterolemic subjects. These results need to be confirmed in larger patient samples and in studies with longer duration.

Molecular and bioinformatical characterization of a novel superfamily of cysteine-rich peptides from arthropods.

PubMed

Zeng, Xian-Chun; Nie, Yao; Luo, Xuesong; Wu, Shifen; Shi, Wanxia; Zhang, Lei; Liu, Yichen; Cao, Hanjun; Yang, Ye; Zhou, Jianping

2013-03-01

The full-length cDNA sequences of two novel cysteine-rich peptides (referred to as HsVx1 and MmKTx1) were obtained from scorpions. The two peptides represent a novel class of cysteine-rich peptides with a unique cysteine pattern. The genomic sequence of HsVx1 is composed of three exons interrupted by two introns that are localized in the mature peptide encoding region and inserted in phase 1 and phase 2, respectively. Such a genomic organization markedly differs from those of other peptides from scorpions described previously. Genome-wide search for the orthologs of HsVx1 identified 59 novel cysteine-rich peptides from arthropods. These peptides share a consistent cysteine pattern with HsVx1. Genomic comparison revealed extensive intron length differences and intronic number and position polymorphisms among the genes of these peptides. Further analysis identified 30 cases of intron sliding, 1 case of intron gain and 22 cases of intron loss occurred with the genes of the HsVx1 and HsVx1-like peptides. It is interesting to see that three HsVx1-like peptides XP_001658928, XP_001658929 and XP_001658930 were derived from a single gene (XP gene): the former two were generated from alternative splicing; the third one was encoded by a DNA region in the reverse complementary strand of the third intron of the XP gene. These findings strongly suggest that the genes of these cysteine-rich peptides were evolved by intron sliding, intron gain/loss, gene recombination and alternative splicing events in response to selective forces without changing their cysteine pattern. The evolution of these genes is dominated by intron sliding and intron loss. Copyright © 2012 Elsevier Inc. All rights reserved.

Heparan Sulfate Differences in Rheumatoid Arthritis versus Healthy Sera

PubMed Central

López-Hoyos, Marcos; Seo, Youjin; Andaya, Armann; Leary, Julie A.

2015-01-01

Heparan sulfate (HS) is a complex and highly variable polysaccharide, expressed ubiquitously on the cell surface as HS proteoglycans (HSPGs), and found in the extracellular matrix as free HS fragments. Its heterogeneity due to various acetylation and sulfation patterns endows a multitude of functions. In animal tissues, HS interacts with a wide range of proteins to mediate numerous biological activities; given its multiple roles in inflammation processes, characterization of HS in human serum has significant potential for elucidating disease mechanisms. Historically, investigation of HS was limited by its low concentration in human serum, together with the complexity of the serum matrix. In this study, we used a modified mass spectrometry method to examine HS disaccharide profiles in the serum of 50 women with rheumatoid arthritis (RA), and compared our results to 51 sera from healthy women. Using various purification methods and online LC-MS/MS, we discovered statistically significant differences in the sulfation and acetylation patterns between populations. Since early diagnosis of RA is considered important in decelerating the disease's progression, identification of specific biomolecule characterizations may provide crucial information towards developing new therapies for suppressing the disease in its early stages. This is the first report of potential glycosaminoglycan biomarkers for RA found in human sera, while acknowledging the obvious fact that a larger population set, and more stringent collection parameters, will need to be investigated in the future. PMID:25217862

Current Alcohol Use is Associated with Sleep Patterns in First-Year College Students.

PubMed

Van Reen, Eliza; Roane, Brandy M; Barker, David H; McGeary, John E; Borsari, Brian; Carskadon, Mary A

2016-06-01

To examine whether differences exist in self-reported sleep patterns and self-reported alcohol use for first-semester college students who do or do not report drinking during the last 6 months (mo) of high school. Participants were 878 first-year college students. Students completed a survey in late May/early June about alcohol use and consequences, during the last 6 mo of high school; they later completed a daily record of sleep behavior and alcohol use across the first 9 weeks of the first semester of college. High school drinking status (past 6 mo) was classified as positive (HS-6 mo+) or negative (HS-6mo-) based on any indication of drinking on the May/June survey. Collegiate drinking was determined from first-semester daily diary alcohol reports as non-drinkers (0 reported drinks), drinkers (one or fewer heavy episodic drinking episodes (HED)), and drinkers reporting more than one HED episode. Sleep patterns were compared for non-drinkers, drinkers, and HED with no high school drinking history (HS-6mo-/HED). In addition, a separate analysis compared sleep patterns for college HED with (HS-6mo+/HED) and without (HS-6mo-/HED) high school self-reported alcohol use. Increased alcohol consumption in the first semester of college was associated with later bedtimes and rise times. We found no association of high school alcohol use and sleep in those with collegiate HED. Later sleep timing in those with greater alcohol use, supports a connection between sleep patterns and alcohol use. Such an early appearance of this connection may herald the development of alcohol use disorder in some individuals. © 2016 Associated Professional Sleep Societies, LLC.

Transgene-free human induced pluripotent stem cell line (HS5-SV.hiPS) generated from cesarean scar-derived fibroblasts.

PubMed

Rungsiwiwut, Ruttachuk; Pavarajarn, Wipawee; Numchaisrika, Pranee; Virutamasen, Pramuan; Pruksananonda, Kamthorn

2016-01-01

Transgene-free human HS5-SV.hiPS line was generated from human cesarean scar-derived fibroblasts using temperature-sensitive Sendai virus vectors carrying Oct4, Sox2, cMyc and Klf4 exogenous transcriptional factors. The viral constructs were eliminated from HS5-SV.hiPS line through heat treatment. Transgene-free HS5-SV.hiPS cells expressed pluripotent associated transcription factors Oct4, Nanog, Sox2, Rex1 and surface markers SSEA-4, TRA-1-60 and OCT4. HS5-SV.hiPS cells formed embryoid bodies and differentiated into three embryonic germ layers in vivo. HS5-SV.hiPS cells maintained their normal karyotype (46, XX) after culture for extended period. HS5-SV.hiPS displayed the similar pattern of DNA fingerprinting to the parenteral scar-derived fibroblasts. Copyright © 2015 The Authors. Published by Elsevier B.V. All rights reserved.

Humic Substances in Organic Wastes and their Effects on Amended Soils

NASA Astrophysics Data System (ADS)

Senesi, N.; Ciavatta, C.; Plaza, C.

2009-04-01

Soil humic substances (HS) are universally recognized to play a major role in a wide number of agronomic and environmental processes. For example, soil HS are able to bind mineral particles together, thus promoting a good soil structure, constitute an important source of nutrients for plants and microorganisms, contribute largely to the acid-base buffering capacity of soils, and exert a marked control on the biological availability, physico-chemical behavior, and environmental fate of toxic metal ions and xenobiotics. For these reasons, the knowledge of the short- and long-term effects of organic amendments on the status, quality, and reactivity of indigenous soil HS is of paramount importance. The objective of this presentation is to provide an overview of the chemical and physico-chemical data available in the literature for the evaluation of the effects of organic wastes of various origin and nature used as soil amendments on the composition, structure, and chemical reactivity of native soil HS. In general, HS-like components of organic wastes are typically characterized by a relatively larger presence of aliphatic, amide, and polysaccharide structures, simple structural components of wide molecular heterogeneity, smaller contents of oxygen, acidic functional groups, and organic free radicals, and smaller degrees of aromatic ring polycondensation, polymerization, and humification than native soil HS. Further, with respect to native soil HS, HS-like fractions from organic wastes generally exhibit smaller binding capacities and affinities for metal ions and organic xenobiotics. Appropriate treatment processes of raw organic wastes able to produce environmentally safe and agronomically efficient soil amendments, such as composting, yield HS-like fractions characterized by chemical and physico-chemical features that approach those of native soil HS. In general, aliphatic, polysaccharide, and lignin structures and S- and N-containing groups of the HS-like fractions of organic wastes can be partially incorporated into native soil HS determining modifications at various extents of their composition, structure, and chemistry. The changes occurred in amended soil HS are more evident when untreated organic materials are used. However, with increasing time after land application, the effects observed become less and less apparent with a clear trend to approach the molecular properties typical of native soil HS.

Can we produce heparin/heparan sulfate biomimetics using "mother-nature" as the gold standard?

PubMed

Farrugia, Brooke L; Lord, Megan S; Melrose, James; Whitelock, John M

2015-03-05

Heparan sulfate (HS) and heparin are glycosaminoglycans (GAGs) that are heterogeneous in nature, not only due to differing disaccharide combinations, but also their sulfate modifications. HS is well known for its interactions with various growth factors and cytokines; and heparin for its clinical use as an anticoagulant. Due to their potential use in tissue regeneration; and the recent adverse events due to contamination of heparin; there is an increased surge to produce these GAGs on a commercial scale. The production of HS from natural sources is limited so strategies are being explored to be biomimetically produced via chemical; chemoenzymatic synthesis methods and through the recombinant expression of proteoglycans. This review details the most recent advances in the field of HS/heparin synthesis for the production of low molecular weight heparin (LMWH) and as a tool further our understanding of the interactions that occur between GAGs and growth factors and cytokines involved in tissue development and repair.

New tools for carbohydrate sulphation analysis: Heparan Sulphate 2- O -sulphotransferase (HS2ST) is a target for small molecule protein kinase inhibitors.

PubMed

Byrne, Dominic P; Li, Yong; Ramakrishnan, Krithika; Barsukov, Igor L; Yates, Edwin A; Eyers, Claire E; Papy-Garcia, Dulcé; Chantepie, Sandrine; Pagadala, Vijayakanth; Lu, Jian; Wells, Carrow; Drewry, David H; Zuercher, William J; Berry, Neil G; Fernig, David G; Eyers, Patrick A

2018-06-22

Sulphation of carbohydrate residues occurs on a variety of glycans destined for secretion, and this modification is essential for efficient matrix-based signal transduction. Heparan sulphate (HS) glycosaminoglycans control physiological functions ranging from blood coagulation to cell proliferation. HS biosynthesis involves membrane-bound Golgi sulphotransferases, including heparan sulphate 2- O -sulphotransferase (HS2ST), which transfers sulphate from the co-factor PAPS (3'-phosphoadenosine 5'-phosphosulphate) to the 2- O  position of a-L-iduronate in the maturing polysaccharide chain. The current lack of simple non-radioactive enzyme assays that can be used to quantify the levels of carbohydrate sulphation hampers kinetic analysis of this process and the discovery of HS2ST inhibitors.  In this paper, we describe a new procedure for thermal shift analysis of purified HS2ST. Using this approach, we quantify HS2ST-catalyzed oligosaccharide sulphation using a novel synthetic fluorescent substrate and screen the Published Kinase Inhibitor Set (PKIS), to evaluate compounds that inhibit catalysis. We report the susceptibility of HS2ST to a variety of cell permeable compounds in vitro , including polyanionic polar molecules, the protein kinase inhibitor rottlerin and oxindole-based RAF kinase inhibitors. In a related study, published back-to-back with this article, we demonstrate that Tyrosyl Protein Sulpho Tranferases (TPSTs) are also inhibited by a variety of protein kinase inhibitors. We propose that appropriately validated small molecule compounds could become new tools for rapid inhibition of glycan (and protein) sulphation in cells, and that protein kinase inhibitors might be repurposed or redesigned for the specific inhibition of HS2ST. ©2018 The Author(s).

Effects of hydrogen sulphide on motility patterns in the rat colon

PubMed Central

Gil, V; Parsons, SP; Gallego, D; Huizinga, JD; Jimenez, M

2013-01-01

Background and Purpose Hydrogen sulphide (H2S) is an endogenous gaseous signalling molecule with putative functions in gastrointestinal motility regulation. Characterization of H2S effects on colonic motility is crucial to establish its potential use as therapeutic agent in the treatment of colonic disorders. Experimental Approach H2S effects on colonic motility were characterized using video recordings and construction of spatio-temporal maps. Microelectrode and muscle bath studies were performed to investigate the mechanisms underlying H2S effects. NaHS was used as the source of H2S. Key Results Rhythmic propulsive motor complexes (RPMCs) and ripples were observed in colonic spatio-temporal maps. Serosal addition of NaHS concentration-dependently inhibited RPMCs. In contrast, NaHS increased amplitude of the ripples without changing their frequency. Therefore, ripples became the predominant motor pattern. Neuronal blockade with lidocaine inhibited RPMCs, which were restored after administration of carbachol. Subsequent addition of NaHS inhibited RPMCs. Luminal addition of NaHS did not modify motility patterns. NaHS inhibited cholinergic excitatory junction potentials, carbachol-induced contractions and hyperpolarized smooth muscle cells, but did not modify slow wave activity. Conclusions and Implications H2S modulated colonic motility inhibiting propulsive contractile activity and enhancing the amplitude of ripples, promoting mixing. Muscle hyperpolarization and inhibition of neurally mediated cholinergic responses contributed to the inhibitory effect on propulsive activity. H2S effects were not related to changes in the frequency of slow wave activity originating in the network of interstitial cells of Cajal located near the submuscular plexus. Luminal H2S did not modify colonic motility probably because of epithelial detoxification. PMID:23297830

Synaptogenesis Is Modulated by Heparan Sulfate in Caenorhabditis elegans

PubMed Central

Lázaro-Peña, María I.; Díaz-Balzac, Carlos A.; Bülow, Hannes E.; Emmons, Scott W.

2018-01-01

The nervous system regulates complex behaviors through a network of neurons interconnected by synapses. How specific synaptic connections are genetically determined is still unclear. Male mating is the most complex behavior in Caenorhabditis elegans. It is composed of sequential steps that are governed by > 3000 chemical connections. Here, we show that heparan sulfates (HS) play a role in the formation and function of the male neural network. HS, sulfated in position 3 by the HS modification enzyme HST-3.1/HS 3-O-sulfotransferase and attached to the HS proteoglycan glypicans LON-2/glypican and GPN-1/glypican, functions cell-autonomously and nonautonomously for response to hermaphrodite contact during mating. Loss of 3-O sulfation resulted in the presynaptic accumulation of RAB-3, a molecule that localizes to synaptic vesicles, and disrupted the formation of synapses in a component of the mating circuits. We also show that the neural cell adhesion protein NRX-1/neurexin promotes and the neural cell adhesion protein NLG-1/neuroligin inhibits the formation of the same set of synapses in a parallel pathway. Thus, neural cell adhesion proteins and extracellular matrix components act together in the formation of synaptic connections. PMID:29559501

Deciphering Transcriptome and Complex Alternative Splicing Transcripts in Mammary Gland Tissues from Cows Naturally Infected with Staphylococcus aureus Mastitis

PubMed Central

Jiang, Qiang; Yang, Chun Hong; Zhang, Yan; Sun, Yan; Li, Rong Ling; Wang, Chang Fa; Zhong, Ji Feng; Huang, Jin Ming

2016-01-01

Alternative splicing (AS) contributes to the complexity of the mammalian proteome and plays an important role in diseases, including infectious diseases. The differential AS patterns of these transcript sequences between the healthy (HS3A) and mastitic (HS8A) cows naturally infected by Staphylococcus aureus were compared to understand the molecular mechanisms underlying mastitis resistance and susceptibility. In this study, using the Illumina paired-end RNA sequencing method, 1352 differentially expressed genes (DEGs) with higher than twofold changes were found in the HS3A and HS8A mammary gland tissues. Gene ontology and KEGG pathway analyses revealed that the cytokine–cytokine receptor interaction pathway is the most significantly enriched pathway. Approximately 16k annotated unigenes were respectively identified in two libraries, based on the bovine Bos taurus UMD3.1 sequence assembly and search. A total of 52.62% and 51.24% annotated unigenes were alternatively spliced in term of exon skipping, intron retention, alternative 5′ splicing and alternative 3ʹ splicing. Additionally, 1,317 AS unigenes were HS3A-specific, whereas 1,093 AS unigenes were HS8A-specific. Some immune-related genes, such as ITGB6, MYD88, ADA, ACKR1, and TNFRSF1B, and their potential relationships with mastitis were highlighted. From Chromosome 2, 4, 6, 7, 10, 13, 14, 17, and 20, 3.66% (HS3A) and 5.4% (HS8A) novel transcripts, which harbor known quantitative trait locus associated with clinical mastitis, were identified. Many DEGs in the healthy and mastitic mammary glands are involved in immune, defense, and inflammation responses. These DEGs, which exhibit diverse and specific splicing patterns and events, can endow dairy cattle with the potential complex genetic resistance against mastitis. PMID:27459697

Cancer Detection in Microarray Data Using a Modified Cat Swarm Optimization Clustering Approach

PubMed

M, Pandi; R, Balamurugan; N, Sadhasivam

2017-12-29

Objective: A better understanding of functional genomics can be obtained by extracting patterns hidden in gene expression data. This could have paramount implications for cancer diagnosis, gene treatments and other domains. Clustering may reveal natural structures and identify interesting patterns in underlying data. The main objective of this research was to derive a heuristic approach to detection of highly co-expressed genes related to cancer from gene expression data with minimum Mean Squared Error (MSE). Methods: A modified CSO algorithm using Harmony Search (MCSO-HS) for clustering cancer gene expression data was applied. Experiment results are analyzed using two cancer gene expression benchmark datasets, namely for leukaemia and for breast cancer. Result: The results indicated MCSO-HS to be better than HS and CSO, 13% and 9% with the leukaemia dataset. For breast cancer dataset improvement was by 22% and 17%, respectively, in terms of MSE. Conclusion: The results showed MCSO-HS to outperform HS and CSO with both benchmark datasets. To validate the clustering results, this work was tested with internal and external cluster validation indices. Also this work points to biological validation of clusters with gene ontology in terms of function, process and component. Creative Commons Attribution License

A reusable device for electrochemical applications of hydrogel supported black lipid membranes.

PubMed

Mech-Dorosz, Agnieszka; Heiskanen, Arto; Bäckström, Sania; Perry, Mark; Muhammad, Haseena B; Hélix-Nielsen, Claus; Emnéus, Jenny

2015-02-01

Black lipid membranes (BLMs) are significant in studies of membrane transport, incorporated proteins/ion transporters, and hence in construction of biosensor devices. Although BLMs provide an accepted mimic of cellular membranes, they are inherently fragile. Techniques are developed to stabilize them, such as hydrogel supports. In this paper, we present a reusable device for studies on hydrogel supported (hs) BLMs. These are formed across an ethylene tetrafluoroethylene (ETFE) aperture array supported by the hydrogel, which is during in situ polymerization covalently "sandwiched" between the ETFE substrate and a gold electrode microchip, thus allowing direct electrochemical studies with the integrated working electrodes. Using electrochemical impedance spectroscopy (EIS), X-ray photoelectron spectroscopy and contact angle measurements, we demonstrate the optimized chemical modifications of the gold electrode microchips and plasma modification of the ETFE aperture arrays facilitating covalent "sandwiching" of the hydrogel. Both fluorescence microscopy and EIS were used to demonstrate the induced spontaneous thinning of a deposited lipid solution, leading to formation of stabilized hsBLMs on average in 10 min. The determined specific membrane capacitance and resistance were shown to vary in the range 0.31-0.49 μF/cm(2) and 45-65 kΩ cm(2), respectively, corresponding to partially solvent containing BLMs with an average life time of 60-80 min. The characterized hsBLM formation and devised equivalent circuit models lead to a schematic model to illustrate lipid molecule distribution in hydrogel-supported apertures. The functionality of stabilized hsBLMs and detection sensitivity of the platform were verified by monitoring the effect of the ion transporter valinomycin.

Muscle atrophy associated with microgravity in rat: Basic data for countermeasures

NASA Astrophysics Data System (ADS)

Falempin, M.; Mounier, Y.

Morphological, contractile properties and myosin heavy chain (MHC) composition of rat soleus muscles were studied after 2 weeks of unloading (HS) and after 2 weeks of HS associated with selective deafferentation (HS + DEAF) at the level L4 and L5. The same significant reductions in muscle mass and tetanic tension were found after HS and HS + DEAF. However, the transformation of the slow-twitch soleus muscle towards a faster type characterized by a decrease in twitch time parameters and an increase in fast-twitch type MHC isoforms in HS did not appear in HS + DEAF conditions. Our results also showed that a pattern similar to firing rate of motoneurones innervating slow-twitch muscles inhibited the slow to fast fiber changes observed during HS. Nevertheless, neither the loss of mass or force output in the HS muscles were prevented by electrostimulation. Immobilization in a stretched position during HS maintained the muscle wet weight, mechanical and electrophoretical characteristics close to control values. We concluded that the decrease in mechanical strains imposed on the muscle during unloading was the main factor for the development of atrophy, while the kinetic changes might be predominantly modulated by the nervous command. These basic data suggested that some experimental conditions such as electrostimulation or stretching, could participate in countermeasure programmes.

Investigation of hypoxia-inducible factor-1α in hippocampal sclerosis: a postmortem study.

PubMed

Feast, Alexandra; Martinian, Lillian; Liu, Joan; Catarino, Claudia B; Thom, Maria; Sisodiya, Sanjay M

2012-08-01

Hypoxia-inducible factor-1α (HIF-1α) is involved in critical aspects of cell survival in response to hypoxia and regulates vascular endothelial growth factor (VEGF) expression. Previous experimental and human studies in epilepsy show up-regulation of VEGF following seizures, although expression of HIF-1α as its potential regulator has not been explored. We used a postmortem (PM) series from patients with epilepsy and hippocampal sclerosis (HS) to investigate patterns of expression of HIF-1α and VEGF and their potential contribution to neuroprotection. In 33 PMs (17 cases with unilateral HS, 3 with bilateral HS, 3 with No-HS, and 10 controls), we quantified neuronal immunolabeling for HIF-1α and VEGF in hippocampal subfields. HIF-1α- and VEGF-immunopositive hippocampal neurones were observed in HS, No-HS, and also in control cases; there was no significant difference in overall labeling between epilepsy cases and controls. In positive cases, HIF-1α and VEGF neuronal labeling localized primarily in CA1, CA4, and CA3 subfields in all groups; significantly more positive neurons were seen in the entorhinal cortex in epilepsy cases (p < 0.05). Labeling lateralized to the side of sclerosis in unilateral HS cases, with significant differences between hemispheres (p < 0.05). There was a trend for high HIF-1α labeling scores in patients with Dravet syndrome without HS and sudden unexpected death in epilepsy (SUDEP) cases, and lower scores with long seizure-free periods prior to death. Hippocampal HIF-1α and VEGF labeling showed a significant correlation. There was neuronal colocalization of HIF-1α and VEGF. Regional expression patterns are in keeping with seizure-related activation of HIF-1α and VEGF. The prominent expression in non-HS cases could support an overall neuroprotective effect. Correlation between HIF-1α and VEGF neuronal immunolabeling supports HIF-1α-mediated induction of VEGF in epilepsy. Wiley Periodicals, Inc. © 2012 International League Against Epilepsy.

Heparan sulfate deficiency in autistic postmortem brain tissue from the subventricular zone of the lateral ventricles.

PubMed

Pearson, Brandon L; Corley, Michael J; Vasconcellos, Amy; Blanchard, D Caroline; Blanchard, Robert J

2013-04-15

Abnormal cellular growth and organization have been characterized in postmortem tissue from brains of autistic individuals, suggestive of pathology in a critical neurogenic niche, the subventricular zone (SVZ) of the brain lateral ventricles (LV). We examined cellular organization, cell proliferation, and constituents of the extracellular matrix such as N-sulfated heparan sulfate (HS) and laminin (LAM) in postmortem brain tissue from the LV-SVZ of young to elderly individuals with autism (n=4) and age-matched typically developing (TD) individuals (n=4) using immunofluorescence techniques. Strong and systematic reductions in HS immunofluorescence were observed in the LV-SVZ of the TD individuals with increasing age. For young through mature, but not elderly, autistic pair members, HS was reduced compared to their matched TDs. Cellular proliferation (Ki67+) was higher in the autistic individual of the youngest age-matched pair. These preliminary data suggesting that HS may be reduced in young to mature autistic individuals are in agreement with previous findings from the BTBR T+tf/J mouse, an animal model of autism; from mice with genetic modifications reducing HS; and with genetic variants in HS-related genes in autism. They suggest that aberrant extracellular matrix glycosaminoglycan function localized to the subventricular zone of the lateral ventricles may be a biomarker for autism, and potentially involved in the etiology of the disorder. Copyright © 2013 Elsevier B.V. All rights reserved.

A Temperature-Based Model for Estimating Monthly Average Daily Global Solar Radiation in China

PubMed Central

Li, Huashan; Cao, Fei; Wang, Xianlong; Ma, Weibin

2014-01-01

Since air temperature records are readily available around the world, the models based on air temperature for estimating solar radiation have been widely accepted. In this paper, a new model based on Hargreaves and Samani (HS) method for estimating monthly average daily global solar radiation is proposed. With statistical error tests, the performance of the new model is validated by comparing with the HS model and its two modifications (Samani model and Chen model) against the measured data at 65 meteorological stations in China. Results show that the new model is more accurate and robust than the HS, Samani, and Chen models in all climatic regions, especially in the humid regions. Hence, the new model can be recommended for estimating solar radiation in areas where only air temperature data are available in China. PMID:24605046

Patterns and Determinants of Temporal Change in High-sensitivity Cardiac Troponin-T: The Atherosclerosis Risk in Communities Cohort Study

PubMed Central

McEvoy, John W; Lazo, Mariana; Chen, Yuan; Shen, Lu; Nambi, Vijay; Hoogeveen, Ron C; Ballantyne, Christie M; Blumenthal, Roger S; Coresh, Josef; Selvin, Elizabeth

2015-01-01

Background Patterns and determinants of temporal change in highly-sensitivity troponin-T (hs-cTNT), a novel measure of subclinical myocardial injury, among asymptomatic persons have not been well characterized. Methods We studied 8,571 ARIC Study participants, free of cardiovascular disease, who had hs-cTNT measured at two time-points, 6 years apart (1990–1992 and 1996–1998). We examined the association of baseline 10-year atherosclerotic cardiovascular (ASCVD) risk-group (<5%, 5–7.4%, ≥7.5%) and individual cardiac risk-factors with change across hs-cTNT categories using Poisson and Multinomial Logistic regression and with mean continuous hs-cTNT change using linear regression. Results Mean age was 57 years and 43% were male. Mean (SD) 6-year hs-cTNT change was higher across increasing ASCVD risk-groups; +1.2 (6.1) ng/L [<5%], +2.1 (5.4) ng/L [5–7.4%], and +2.8 (8.8) ng/L [≥7.5%]. Major baseline determinants of temporal hs-cTNT increases were; age, male gender, hypertension, diabetes, and obesity. In addition, the relative risk (RR) of incident elevated hs-cTNT (≥14ng/L) was 1.46 (95% CI 1.1–2.0) for persons with sustained hypertension compared to those who remained normotensive. Results for sustained obesity (RR 1.65 [1.19–2.29]) and hyperglycemia (RR 1.76 [1.16–2.67]) were similar. These associations were generally stronger after accounting for survival bias. However, smoking, LDL-cholesterol and triglycerides were not associated with hs-cTNT change. HDL-cholesterol was associated with declining hs-cTNT. Conclusions Persons in higher ASCVD risk-groups were more likely to have increases in hs-cTNT over 6 years of follow-up. The modifiable risk-factors primarily driving this association were diabetes, hypertension, and obesity; particularly when they were persistently elevated over follow-up. Future studies are needed to determine whether modifying these risk factors can prevent progression of subclinical myocardial injury. PMID:25880403

Functional visualization and disruption of targeted genes using CRISPR/Cas9-mediated eGFP reporter integration in zebrafish.

PubMed

Ota, Satoshi; Taimatsu, Kiyohito; Yanagi, Kanoko; Namiki, Tomohiro; Ohga, Rie; Higashijima, Shin-Ichi; Kawahara, Atsuo

2016-10-11

The CRISPR/Cas9 complex, which is composed of a guide RNA (gRNA) and the Cas9 nuclease, is useful for carrying out genome modifications in various organisms. Recently, the CRISPR/Cas9-mediated locus-specific integration of a reporter, which contains the Mbait sequence targeted using Mbait-gRNA, the hsp70 promoter and the eGFP gene, has allowed the visualization of the target gene expression. However, it has not been ascertained whether the reporter integrations at both targeted alleles cause loss-of-function phenotypes in zebrafish. In this study, we have inserted the Mbait-hs-eGFP reporter into the pax2a gene because the disruption of pax2a causes the loss of the midbrain-hindbrain boundary (MHB) in zebrafish. In the heterozygous Tg[pax2a-hs:eGFP] embryos, MHB formed normally and the eGFP expression recapitulated the endogenous pax2a expression, including the MHB. We observed the loss of the MHB in homozygous Tg[pax2a-hs:eGFP] embryos. Furthermore, we succeeded in integrating the Mbait-hs-eGFP reporter into an uncharacterized gene epdr1. The eGFP expression in heterozygous Tg[epdr1-hs:eGFP] embryos overlapped the epdr1 expression, whereas the distribution of eGFP-positive cells was disorganized in the MHB of homozygous Tg[epdr1-hs:eGFP] embryos. We propose that the locus-specific integration of the Mbait-hs-eGFP reporter is a powerful method to investigate both gene expression profiles and loss-of-function phenotypes.

Functional visualization and disruption of targeted genes using CRISPR/Cas9-mediated eGFP reporter integration in zebrafish

PubMed Central

Ota, Satoshi; Taimatsu, Kiyohito; Yanagi, Kanoko; Namiki, Tomohiro; Ohga, Rie; Higashijima, Shin-ichi; Kawahara, Atsuo

2016-01-01

The CRISPR/Cas9 complex, which is composed of a guide RNA (gRNA) and the Cas9 nuclease, is useful for carrying out genome modifications in various organisms. Recently, the CRISPR/Cas9-mediated locus-specific integration of a reporter, which contains the Mbait sequence targeted using Mbait-gRNA, the hsp70 promoter and the eGFP gene, has allowed the visualization of the target gene expression. However, it has not been ascertained whether the reporter integrations at both targeted alleles cause loss-of-function phenotypes in zebrafish. In this study, we have inserted the Mbait-hs-eGFP reporter into the pax2a gene because the disruption of pax2a causes the loss of the midbrain-hindbrain boundary (MHB) in zebrafish. In the heterozygous Tg[pax2a-hs:eGFP] embryos, MHB formed normally and the eGFP expression recapitulated the endogenous pax2a expression, including the MHB. We observed the loss of the MHB in homozygous Tg[pax2a-hs:eGFP] embryos. Furthermore, we succeeded in integrating the Mbait-hs-eGFP reporter into an uncharacterized gene epdr1. The eGFP expression in heterozygous Tg[epdr1-hs:eGFP] embryos overlapped the epdr1 expression, whereas the distribution of eGFP-positive cells was disorganized in the MHB of homozygous Tg[epdr1-hs:eGFP] embryos. We propose that the locus-specific integration of the Mbait-hs-eGFP reporter is a powerful method to investigate both gene expression profiles and loss-of-function phenotypes. PMID:27725766

Review: Hippocampal sclerosis in epilepsy: a neuropathology review

PubMed Central

Thom, Maria

2014-01-01

Hippocampal sclerosis (HS) is a common pathology encountered in mesial temporal lobe epilepsy (MTLE) as well as other epilepsy syndromes and in both surgical and post-mortem practice. The 2013 International League Against Epilepsy (ILAE) classification segregates HS into typical (type 1) and atypical (type 2 and 3) groups, based on the histological patterns of subfield neuronal loss and gliosis. In addition, granule cell reorganization and alterations of interneuronal populations, neuropeptide fibre networks and mossy fibre sprouting are distinctive features of HS associated with epilepsies; they can be useful diagnostic aids to discriminate from other causes of HS, as well as highlighting potential mechanisms of hippocampal epileptogenesis. The cause of HS remains elusive and may be multifactorial; the contribution of febrile seizures, genetic susceptibility, inflammatory and neurodevelopmental factors are discussed. Post-mortem based research in HS, as an addition to studies on surgical samples, has the added advantage of enabling the study of the wider network changes associated with HS, the long-term effects of epilepsy on the pathology and associated comorbidities. It is likely that HS is heterogeneous in aspects of its cause, epileptogenetic mechanisms, network alterations and response to medical and surgical treatments. Future neuropathological studies will contribute to better recognition and understanding of these clinical and patho-aetiological subtypes of HS. PMID:24762203

VEZF1 Elements Mediate Protection from DNA Methylation

PubMed Central

Strogantsev, Ruslan; Gaszner, Miklos; Hair, Alan; Felsenfeld, Gary; West, Adam G.

2010-01-01

There is growing consensus that genome organization and long-range gene regulation involves partitioning of the genome into domains of distinct epigenetic chromatin states. Chromatin insulator or barrier elements are key components of these processes as they can establish boundaries between chromatin states. The ability of elements such as the paradigm β-globin HS4 insulator to block the range of enhancers or the spread of repressive histone modifications is well established. Here we have addressed the hypothesis that a barrier element in vertebrates should be capable of defending a gene from silencing by DNA methylation. Using an established stable reporter gene system, we find that HS4 acts specifically to protect a gene promoter from de novo DNA methylation. Notably, protection from methylation can occur in the absence of histone acetylation or transcription. There is a division of labor at HS4; the sequences that mediate protection from methylation are separable from those that mediate CTCF-dependent enhancer blocking and USF-dependent histone modification recruitment. The zinc finger protein VEZF1 was purified as the factor that specifically interacts with the methylation protection elements. VEZF1 is a candidate CpG island protection factor as the G-rich sequences bound by VEZF1 are frequently found at CpG island promoters. Indeed, we show that VEZF1 elements are sufficient to mediate demethylation and protection of the APRT CpG island promoter from DNA methylation. We propose that many barrier elements in vertebrates will prevent DNA methylation in addition to blocking the propagation of repressive histone modifications, as either process is sufficient to direct the establishment of an epigenetically stable silent chromatin state. PMID:20062523

Development and initial psychometric evaluation of patient-reported outcome questionnaires to evaluate the symptoms and impact of hidradenitis suppurativa.

PubMed

Kimball, Alexa B; Sundaram, Murali; Banderas, Benjamin; Foley, Catherine; Shields, Alan L

2018-03-01

Two patient-reported outcome (PRO) questionnaires, the Hidradenitis Suppurativa Symptom Assessment (HSSA) and Hidradenitis Suppurativa Impact Assessment (HSIA), were developed to measure signs, symptoms and impacts of HS in treatment efficacy studies. In accordance with FDA guidelines and published best practices, four stages of research were conducted to create the questionnaires: concept elicitation, questionnaire construction, content evaluation and psychometric evaluation. Subjects (N = 20) who participated in the concept elicitation stage reported 15 unique HS-related signs and symptoms and 51 impacts. Following this, eight sign and symptom concepts and 21 impacts were selected for construction of the HSSA and HSIA, respectively. During content evaluation, cognitive debriefing interviews with HS subjects (N = 20) confirmed subjects could read, comprehend and meaningfully respond to both questionnaires. Modifications made after this stage of work resulted in a nine-item HSSA and a 17-item HSIA. The HSSA and HSIA were subsequently entered into a US-based observational study (N = 40), and the scores produced by each were found to be reliable, construct valid, and able to distinguish among clinically distinct groups. The HSSA and HSIA are content-valid, HS-specific, PRO questionnaires with demonstrated ability to generate reliable, valid scores when administered to patients with HS in a research setting.

Biotechnological engineering of heparin/heparan sulphate: a novel area of multi-target drug discovery.

PubMed

Rusnati, Marco; Oreste, Pasqua; Zoppetti, Giorgio; Presta, Marco

2005-01-01

Heparin is a sulphated glycosaminoglycan currently used as an anticoagulant and antithrombotic drug. It consists largely of 2-O-sulphated IdoA not l&r arrow N, 6-O-disulphated GlcN disaccharide units. Other disaccharides containing unsulphated IdoA or GlcA and N-sulphated or N-acetylated GlcN are also present as minor components. This heterogeneity is more pronounced in heparan sulphate (HS), where the low-sulphated disaccharides are the most abundant. Heparin/HS bind to a variety of biologically active polypeptides, including enzymes, growth factors and cytokines, and viral proteins. This capacity can be exploited to design multi-target heparin/HS-derived drugs for pharmacological interventions in a variety of pathologic conditions besides coagulation and thrombosis, including neoplasia and viral infection. The capsular K5 polysaccharide from Escherichia coli has the same structure as the heparin precursor N-acetyl heparosan. The possibility of producing K5 polysaccharide derivatives by chemical and enzymatic modifications, thus generating heparin/HS-like compounds, has been demonstrated. These K5 polysaccharide derivatives are endowed with different biological properties, including anticoagulant/antithrombotic, antineoplastic, and anti-AIDS activities. Here, the literature data are discussed and the possible therapeutic implications for this novel class of multi-target "biotechnological heparin/HS" molecules are outlined.

Examining Fundamental Movement Competency and Closed-Chain Upper-Extremity Dynamic Balance in Swimmers.

PubMed

Bullock, Garrett S; Brookreson, Nate; Knab, Amy M; Butler, Robert J

2017-06-01

Abnormal fundamental movement patterns and upper-quarter dynamic balance are proposed mechanisms affecting athletic performance and injury risk. There are few studies investigating functional movement and closed-chain upper-extremity dynamic stability in swimmers. The purpose of this study was to determine differences in fundamental movement competency and closed-chain upper-extremity dynamic balance, using the Functional Movement Screen (FMS) and Upper-Quarter Y Balance Test (YBT-UQ), of high school (HS; n = 70) and collegiate (COL; n = 70) swimmers. Variables included the individual movement tests on the FMS and the average normalized reach (percent limb length [%LL]) for each direction, with the YBT-UQ. Statistical analysis was completed using a chi square for the independent test scores on the FMS while independent samples t-test to examine performance on the YBT-UQ (p ≤ 0.05). HS swimmers exhibited a statistically significant greater percentage of below average performance (score of 0 or 1) on the following FMS tests: lunge (HS: 22.9%, COL: 4.3%), hurdle step (HS: 31.4%, COL: 7.1%), and push-up (HS: 61.4%, COL: 31.4%). Furthermore, COL males performed worse in the lunge (male: 9%, female: 0%), whereas COL females had poorer efficiency in the push-up (male: 17.6%, female: 44%). Significant effects of competition level and sex were observed in YBT-UQ medial reach (HS: female 92.06, male 101.63; COL: female 101.3, male 101.5% LL). Individual fundamental movement patterns that involved lumbopelvic neuromuscular control differed between HS and COL swimmers. General upper-extremity dynamic balance differed between competition levels. These data may be helpful in understanding injury and performance-based normative data for participation and return to swimming.

Increased low-grade inflammation and plasminogen-activator inhibitor-1 level in non-dippers with sleep apnea syndrome

PubMed Central

Ishikawa, Joji; Hoshide, Satoshi; Eguchi, Kazuo; Ishikawa, Shizukiyo; Pickering, Thomas G; Shimada, Kazuyuki; Kario, Kazuomi

2010-01-01

Objective Patients with sleep apnea syndrome (SAS) have an increased risk of cardiovascular events and frequently show a non-dipper pattern (blunted nocturnal decline <10%) of systolic blood pressure (BP). We investigated neurohumoral activation and risk factors in relation to nocturnal BP dipping pattern and SAS. Methods We conducted sleep polysomnography and ambulatory BP monitoring, and measured high-sensitivity C-reactive protein (hsCRP), tissue-type plasminogen activator inhibitor-1 (PAI-1), and neurohumoral factors in 121 outpatients with suspected SAS, who were classified in 4 groups depending on the presence or absence of dipping/non-dipping and SAS. Results Non-dippers with SAS had higher hsCRP (overall P<0.001), PAI-1 (overall P=0.004), and aldosterone levels (overall P=0.010) than any of the other 3 groups. After adjustment for significant covariates such as age, sex, body mass index, waist circumference, smoking, alcohol drinking, aspirin use, presence of DM, and insulin, non-dippers with SAS still had a higher hsCRP level than non-dippers without SAS (geometric mean: 1.47 vs. 0.37 mg/L, P=0.001). In multiple linear regression analysis controlling for confounding factors that related with SAS, hsCRP was significantly correlated with 3% oxygen desaturation index (P=0.047). PAI-1 was also highest in the non-dippers with SAS, but this was not independent of obesity. PAI-1 was correlated with insulin (r=0.32, P=0.002) and hsCRP levels (r=0.26, P=0.005). Conclusion Non-dipper status was associated with an increased hsCRP in patients who also had SAS, but not in those who did not, and hsCRP was closely affected by the desaturation level. PAI-1 is also increased in non-dippers with SAS, and is related to insulin and hsCRP. PMID:18475156

Hereditary spherocytosis and elliptocytosis associated with prosthetic heart valve replacement: rheological study of erythrocyte modifications.

PubMed

Caprari, Patrizia; Tarzia, Anna; Mojoli, Giorgio; Cianciulli, Paolo; Mannella, Emilio; Martorana, Maria Cristina

2009-04-01

The implantation of a prosthetic heart valve (HVP) in patients with hereditary spherocytosis (HS) and hereditary elliptocytosis (HE) is rare, and the changes in the structure and deformability of erythrocytes that follow implantation in these patients have been poorly described. In the present study, the erythrocytes in HS and HE patients with mechanical HVP were compared to the erythrocytes in patients with only congenital membrane defects, in terms of biochemical modifications and rheological behaviour. Integral and cytoskeletal erythrocyte membrane proteins were studied, and blood viscosity (shear rate/shear stress ratio), aggregation ratio [eta(1 s(-1))/eta(200 s(-1))], and red cell visco-elasticity were determined. Valve replacement with a mechanical prosthesis worsened anaemia and resulted in a change in haemolysis, from sub-clinical to evident. The rheological investigation of erythrocytes from HS patients confirmed the characteristic increased viscosity and aggregation ratio and the decreased deformability. The rheological behaviour of erythrocytes from patients with HVP showed a decrease in viscosity and an increase in elastic modulus. In these patients, the prosthesis seems to have induced traumatic damage to the erythrocyte membrane, leading to fragmentation and lysis, which in turn modified rheological parameters. The biochemical and rheological investigation allowed us to understand the clinical and haematological pictures of the patients and to describe the role played by different factors in haemolytic anaemia.

Adeno-associated virus type 2 binding study on model heparan sulfate surface

NASA Astrophysics Data System (ADS)

Negishi, Atsuko; Liu, Jian; McCarty, Douglas; Samulski, Jude; Superfine, Richard

2003-11-01

Understanding the mechanisms involved in virus infections is useful in its application in areas such as gene therapy, drug development and delivery, and biosensors. In collaboration with UNC Gene Therapy Center and School of Pharmacy, we are specifically looking at the interaction between human parvovirus adeno-associated virus type 2 (AAV2), a potential viral vector, and heparan sulfate proteoglycan (HSPG), a known cell surface receptor for AAV2. Recent development in glycobiology has shown that some protein-polysaccharide binding is sugar sequence dependent. Heparan sulfate (HS) is a polysaccharide chain of sulfated iduronic/glucuronic and sulfate glucosamine residues and can be differentiated into sequence specific structures by enzymes. These enzymatic modifications, known as heparan sulfate sulfotransferase modified modifications, have been shown to change the biological nature of heparan sulfate such as specific binding to proteins and viruses. For understanding HS-assisted viral infection mechanisms, we are interested in investigating the binding affinity and stability of AAV to different HS structures. We have developed a model heparan sulfate surface in which AAV adsorption studies are done and analyzed using the atomic force microscope (AFM). In addition, a miniArray assay has been created to facilitate to this study. Adsorption studies are done in 4 white LED wells with approximately 3 mm2 reaction areas which minimize sample use and waste.

Hyperspectral Imaging Using Flexible Endoscopy for Laryngeal Cancer Detection

PubMed Central

Regeling, Bianca; Thies, Boris; Gerstner, Andreas O. H.; Westermann, Stephan; Müller, Nina A.; Bendix, Jörg; Laffers, Wiebke

2016-01-01

Hyperspectral imaging (HSI) is increasingly gaining acceptance in the medical field. Up until now, HSI has been used in conjunction with rigid endoscopy to detect cancer in vivo. The logical next step is to pair HSI with flexible endoscopy, since it improves access to hard-to-reach areas. While the flexible endoscope’s fiber optic cables provide the advantage of flexibility, they also introduce an interfering honeycomb-like pattern onto images. Due to the substantial impact this pattern has on locating cancerous tissue, it must be removed before the HS data can be further processed. Thereby, the loss of information is to minimize avoiding the suppression of small-area variations of pixel values. We have developed a system that uses flexible endoscopy to record HS cubes of the larynx and designed a special filtering technique to remove the honeycomb-like pattern with minimal loss of information. We have confirmed its feasibility by comparing it to conventional filtering techniques using an objective metric and by applying unsupervised and supervised classifications to raw and pre-processed HS cubes. Compared to conventional techniques, our method successfully removes the honeycomb-like pattern and considerably improves classification performance, while preserving image details. PMID:27529255

Hyperspectral Imaging Using Flexible Endoscopy for Laryngeal Cancer Detection.

PubMed

Regeling, Bianca; Thies, Boris; Gerstner, Andreas O H; Westermann, Stephan; Müller, Nina A; Bendix, Jörg; Laffers, Wiebke

2016-08-13

Hyperspectral imaging (HSI) is increasingly gaining acceptance in the medical field. Up until now, HSI has been used in conjunction with rigid endoscopy to detect cancer in vivo. The logical next step is to pair HSI with flexible endoscopy, since it improves access to hard-to-reach areas. While the flexible endoscope's fiber optic cables provide the advantage of flexibility, they also introduce an interfering honeycomb-like pattern onto images. Due to the substantial impact this pattern has on locating cancerous tissue, it must be removed before the HS data can be further processed. Thereby, the loss of information is to minimize avoiding the suppression of small-area variations of pixel values. We have developed a system that uses flexible endoscopy to record HS cubes of the larynx and designed a special filtering technique to remove the honeycomb-like pattern with minimal loss of information. We have confirmed its feasibility by comparing it to conventional filtering techniques using an objective metric and by applying unsupervised and supervised classifications to raw and pre-processed HS cubes. Compared to conventional techniques, our method successfully removes the honeycomb-like pattern and considerably improves classification performance, while preserving image details.

Response of humic-reducing microorganisms to the redox properties of humic substance during composting.

PubMed

Zhao, Xinyu; He, Xiaosong; Xi, Beidou; Gao, Rutai; Tan, Wenbing; Zhang, Hui; Huang, Caihong; Li, Dan; Li, Meng

2017-12-01

Humic substance (HS) could be utilized by humus-reducing microorganisms (HRMs) as the terminal acceptors. Meanwhile, the reduction of HS can support the microbial growth. This process would greatly affect the redox conversion of inorganic and organic pollutants. However, whether the redox properties of HS lined with HRMs community during composting still remain unclear. This study aimed to assess the relationships between the redox capability of HS [i.e. humic acids (HA) and fulvic acids (FA)] and HRMs during composting. The results showed that the changing patterns of electron accepting capacity and electron donating capacity of HS were diverse during seven composting. Electron transfer capacities (ETC) of HA was significantly correlated with the functional groups (i.e. alkyl C, O-alkyl C, aryl C, carboxylic C, aromatic C), aromaticity and molecular weight of HA. Aromatic C, phenols, aryl C, carboxylic C, aromaticity and molecular weight of HS were the main structuralfeatures associated with the ETC of FA. Ten key genera of HRMs were found significantly determine these redox-active functional groups of HS during composting, thus influencing the ETC of HS in composts. In addition, a regulating method was suggested to enhance the ETC of HS during composting based on the relationships between the key HRMs and redox-active functional groups as well as environmental variables. Copyright © 2017 Elsevier Ltd. All rights reserved.

The heparin/heparan sulfate sequence that interacts with cyclophilin B contains a 3-O-sulfated N-unsubstituted glucosamine residue.

PubMed

Vanpouille, Christophe; Deligny, Audrey; Delehedde, Maryse; Denys, Agnès; Melchior, Aurélie; Liénard, Xavier; Lyon, Malcolm; Mazurier, Joël; Fernig, David G; Allain, Fabrice

2007-08-17

Many of the biological functions of heparan sulfate (HS) proteoglycans can be attributed to specialized structures within HS moieties, which are thought to modulate binding and function of various effector proteins. Cyclophilin B (CyPB), which was initially identified as a cyclosporin A-binding protein, triggers migration and integrin-mediated adhesion of peripheral blood T lymphocytes by a mechanism dependent on interaction with cell surface HS. Here we determined the structural features of HS that are responsible for the specific binding of CyPB. In addition to the involvement of 2-O,6-O, and N-sulfate groups, we also demonstrated that binding of CyPB was dependent on the presence of N-unsubstituted glucosamine residues (GlcNH2), which have been reported to be precursors for sulfation by 3-O-sulfotransferases-3 (3-OST-3). Interestingly, 3-OST-3B isoform was found to be the main 3-OST isoenzyme expressed in peripheral blood T lymphocytes and Jurkat T cells. Moreover, down-regulation of the expression of 3-OST-3 by RNA interference potently reduced CyPB binding and consequent activation of p44/42 mitogen-activated protein kinases. Altogether, our results strongly support the hypothesis that 3-O-sulfation of GlcNH2 residues could be a key modification that provides specialized HS structures for CyPB binding to responsive cells. Given that 3-O-sulfation of GlcNH2-containing HS by 3-OST-3 also provides binding sites for glycoprotein gD of herpes simplex virus type I, these findings suggest an intriguing structural linkage between the HS sequences involved in CyPB binding and viral infection.

The Role of Heparan Sulfate Proteoglycans in Optic Disc and Stalk Morphogenesis

PubMed Central

Cai, Zhigang; Grobe, Kay; Zhang, Xin

2014-01-01

Background Heparan sulfate proteoglycans (HSPG) are important for embryonic development via the regulation of gradient formation and signaling of multiple growth factors and morphogens. Previous studies have shown that Bmp/Shh/Fgf signaling are required for the regionalization of the optic vesicle (OV) and for the closure of the optic fissure (OF), the disturbance of which underlie ocular anomalies such as microphthalmia, coloboma and optic nerve hypoplasia. Results To study HSPG-dependent coordination of these signaling pathways during mammalian visual system development, we have generated a series of OV-specific mutations in the heparan sulfate (HS) N-sulfotransferase genes (Ndst1 and Ndst2) and HS O-sulfotransferase genes (Hs2st, Hs6st1 and Hs6st2) in mice. Interestingly, the resulting HS undersulfation still allowed for normal retinal neurogenesis and optic fissure closure, but led to defective optic disc and stalk development. The adult mutant animals further developed optic nerve aplasia/hypoplasia and displayed retinal degeneration. We observed that MAPK/ERK signaling was down-regulated in Ndst mutants, and consistent with this, HS-related optic nerve morphogenesis defects in mutant mice could partially be rescued by constitutive Kras activation. Conclusions These results suggest that HSPGs, depending on their HS sulfation pattern, regulate multiple signaling pathways in optic disc and stalk morphogenesis. PMID:24753163

Hippocampal sclerosis of aging is a key Alzheimer's disease mimic: clinical-pathologic correlations and comparisons with both alzheimer's disease and non-tauopathic frontotemporal lobar degeneration.

PubMed

Brenowitz, Willa D; Monsell, Sarah E; Schmitt, Frederick A; Kukull, Walter A; Nelson, Peter T

2014-01-01

Hippocampal sclerosis of aging (HS-Aging) neuropathology was observed in more than 15% of aged individuals in prior studies. However, much remains unknown about the clinical correlates of HS-Aging pathology or the association(s) between HS-Aging, Alzheimer's disease (AD), and frontotemporal lobar degeneration (FTLD) pathology. Clinical and comorbid pathological features linked to HS-Aging pathology were analyzed using National Alzheimer's Coordinating Center (NACC) data. From autopsy data extending back to 1990 (n = 9,817 participants), the neuropathological diagnoses were evaluated from American AD Centers (ADCs). Among participants who died between 2005-2012 (n = 1,422), additional analyses identified clinical and pathological features associated with HS-Aging pathology. We also compared cognitive testing and longevity outcomes between HS-Aging cases and a subsample with non-tauopathy FTLD (n = 210). Reporting of HS-Aging pathology increased dramatically among ADCs in recent years, to nearly 20% of autopsies in 2012. Participants with relatively "pure" HS-Aging pathology were often diagnosed clinically as having probable (68%) or possible (15%) AD. However, the co-occurrence of HS-Aging pathology and AD neuropathology (AD-NP) did not indicate any pattern of correlation between the two pathologies. Compared with other pathologies, participants with HS-Aging pathology had higher overall cognitive/functional ability (versus AD-NP) and verbal fluency (versus both AD-NP and FTLD) but similar episodic memory impairment at one clinic visit 2-5 years prior to death. Patients with HS-Aging live considerably longer than patients with non-tauopathy FTLD. We conclude that the manifestations of HS-Aging, increasingly recognized in recent years, probably indicate a separate disease process of direct relevance to patient care, dementia research, and clinical trials.

Hippocampal sclerosis of aging is a key Alzheimer's disease mimic: clinical-pathologic correlations and comparisons with both Alzheimer's disease and non-tauopathic frontotemporal lobar degeneration

PubMed Central

Brenowitz, Willa D.; Monsell, Sarah E.; Schmitt, Frederick A.; Kukull, Walter A.; Nelson, Peter T.

2013-01-01

Hippocampal sclerosis of aging (HS-Aging) neuropathology was observed in more than 15% of aged individuals in prior studies. However, much remains unknown about the clinical correlates of HS-Aging pathology or the association(s) between HS-Aging, Alzheimer's disease (AD), and frontotemporal lobar degeneration (FTLD) pathology. Clinical and comorbid pathological features linked to HS-Aging pathology were analyzed using National Alzheimer's Coordinating Center (NACC) data. From autopsy data extending back to 1990 (N=9,817 participants), the neuropathologic diagnoses were evaluated from American AD Centers (ADCs). Among participants who died between 2005-2012 (N=1,422), additional analyses identified clinical and pathological features associated with HS-Aging pathology. We also compared cognitive testing and longevity outcomes between HS-Aging cases and a subsample with non-tauopathy FTLD (N=210). Reporting of HS pathology increased dramatically among ADCs in recent years, to nearly 20% of autopsies in 2012. Participants with relatively “pure” HS-Aging pathology were often diagnosed clinically as having probable (68%) or possible (15%) AD. However, the co-occurrence of HS-Aging pathology and AD neuropathology (AD-NP) did not indicate any pattern of correlation between the two pathologies. Compared other pathologies, participants with HS-Aging pathology had higher overall cognitive/functional ability (versus AD-NP) and verbal fluency (versus both AD-NP and FTLD) but similar episodic memory impairment at one clinic visit 2 -5 years prior to death. Patients with HS-Aging live considerably longer than patients with non-tauopathy FTLD. We conclude that the manifestations of HS-Aging, increasingly recognized in recent years, probably indicate a separate disease process of direct relevance to patient care, dementia research, and clinical trials. PMID:24270205

C5-epimerase and 2-O-sulfotransferase associate in vitro to generate contiguous epimerized and 2-O-sulfated heparan sulfate domains.

PubMed

Préchoux, Aurélie; Halimi, Célia; Simorre, Jean-Pierre; Lortat-Jacob, Hugues; Laguri, Cédric

2015-04-17

Heparan sulfate (HS), a complex polysaccharide of the cell surface, is endowed with the remarkable ability to bind numerous proteins and, as such, regulates a large variety of biological processes. Protein binding depends on HS structure; however, in the absence of a template driving its biosynthesis, the mechanism by which protein binding sequences are assembled remains poorly known. Here, we developed a chemically defined 13C-labeled substrate and NMR based experiments to simultaneously follow in real time the activity of HS biosynthetic enzymes and characterize the reaction products. Using this new approach, we report that the association of C5-epimerase and 2-O-sulfotransferase, which catalyze the production of iduronic acid and its 2-O-sulfation, respectively, is necessary to processively generate extended sequences of contiguous IdoA2S-containing disaccharides, whereas modifications are randomly introduced when the enzymes are uncoupled. These data shed light on the mechanisms by which HS motifs are generated during biosynthesis. They support the view that HS structure assembly is controlled not only by the availability of the biosynthetic enzymes but also by their physical association, which in the case of the C5-epimerase and 2-O-sulfotransferase was characterized by an affinity of 80 nM as demonstrated by surface plasmon resonance experiments.

High sodium diet converts renal proteoglycans into pro-inflammatory mediators in rats

PubMed Central

Shrestha, Pragyi; Sarpong, Kwaku A.; Yazdani, Saleh; el Masri, Rana; de Jong, Wilhelmina H. A.; Navis, Gerjan; Vivès, Romain R.; van den Born, Jacob

2017-01-01

Background High dietary sodium aggravates renal disease by affecting blood pressure and by its recently shown pro-inflammatory and pro-fibrotic effects. Moreover, pro-inflammatory modification of renal heparan sulfate (HS) can induce tissue remodeling. We aim to investigate if high sodium intake in normotensive rats converts renal HS into a pro-inflammatory phenotype, able to bind more sodium and orchestrate inflammation, fibrosis and lymphangiogenesis. Methods Wistar rats received a normal diet for 4 weeks, or 8% NaCl diet for 2 or 4 weeks. Blood pressure was monitored, and plasma, urine and tissue collected. Tissue sodium was measured by flame spectroscopy. Renal HS and tubulo-interstitial remodeling were studied by biochemical, immunohistochemical and qRT-PCR approaches. Results High sodium rats showed a transient increase in blood pressure (week 1; p<0.01) and increased sodium excretion (p<0.05) at 2 and 4 weeks compared to controls. Tubulo-interstitial T-cells, myofibroblasts and mRNA levels of VCAM1, TGF-β1 and collagen type III significantly increased after 4 weeks (all p<0.05). There was a trend for increased macrophage infiltration and lymphangiogenesis (both p = 0.07). Despite increased dermal sodium over time (p<0.05), renal concentrations remained stable. Renal HS of high sodium rats showed increased sulfation (p = 0.05), increased L-selectin binding to HS (p<0,05), and a reduction of sulfation-sensitive anti-HS mAbs JM403 (p<0.001) and 10E4 (p<0.01). Hyaluronan expression increased under high salt conditions (p<0.01) without significant changes in the chondroitin sulfate proteoglycan versican. Statistical analyses showed that sodium-induced tissue remodeling responses partly correlated with observed HS changes. Conclusion We show that high salt intake by healthy normotensive rats convert renal HS into high sulfated pro-inflammatory glycans involved in tissue remodeling events, but not in increased sodium storage. PMID:28594849

Human homosexuality: a paradigmatic arena for sexually antagonistic selection?

PubMed

Camperio Ciani, Andrea; Battaglia, Umberto; Zanzotto, Giovanni

2015-01-29

Sexual conflict likely plays a crucial role in the origin and maintenance of homosexuality in our species. Although environmental factors are known to affect human homosexual (HS) preference, sibling concordances and population patterns related to HS indicate that genetic components are also influencing this trait in humans. We argue that multilocus, partially X-linked genetic factors undergoing sexually antagonistic selection that promote maternal female fecundity at the cost of occasional male offspring homosexuality are the best candidates capable of explaining the frequency, familial clustering, and pedigree asymmetries observed in HS male proband families. This establishes male HS as a paradigmatic example of sexual conflict in human biology. HS in females, on the other hand, is currently a more elusive phenomenon from both the empirical and theoretical standpoints because of its fluidity and marked environmental influence. Genetic and epigenetic mechanisms, the latter involving sexually antagonistic components, have been hypothesized for the propagation and maintenance of female HS in the population. However, further data are needed to truly clarify the evolutionary dynamics of this trait. Copyright © 2015 Cold Spring Harbor Laboratory Press; all rights reserved.

Human Homosexuality: A Paradigmatic Arena for Sexually Antagonistic Selection?

PubMed Central

Ciani, Andrea Camperio; Battaglia, Umberto; Zanzotto, Giovanni

2015-01-01

Sexual conflict likely plays a crucial role in the origin and maintenance of homosexuality in our species. Although environmental factors are known to affect human homosexual (HS) preference, sibling concordances and population patterns related to HS indicate that genetic components are also influencing this trait in humans. We argue that multilocus, partially X-linked genetic factors undergoing sexually antagonistic selection that promote maternal female fecundity at the cost of occasional male offspring homosexuality are the best candidates capable of explaining the frequency, familial clustering, and pedigree asymmetries observed in HS male proband families. This establishes male HS as a paradigmatic example of sexual conflict in human biology. HS in females, on the other hand, is currently a more elusive phenomenon from both the empirical and theoretical standpoints because of its fluidity and marked environmental influence. Genetic and epigenetic mechanisms, the latter involving sexually antagonistic components, have been hypothesized for the propagation and maintenance of female HS in the population. However, further data are needed to truly clarify the evolutionary dynamics of this trait. PMID:25635045

Occurrence of Chronic Pelvic Pain, Abnormal Uterine Bleeding, and Hysterectomy Post-procedure among Women Who Have Undergone Female Sterilization Procedures: A Retrospective Claims Analysis of Commercially Insured Women in the US.

PubMed

Carney, Patricia I; Yao, Jianying; Lin, Jay; Law, Amy

To evaluate the frequency of chronic pelvic pain (CPP), abnormal uterine bleeding (AUB), and hysterectomy after hysteroscopic sterilization (HS) or laparoscopic sterilization (LS) in the United States. Retrospective cohort study (Canadian Task Force classification II-2). Commercially insured women. Women (aged 18-49 years) with claims for HS or LS from January 1, 2010 to December 31, 2012 were identified from the MarketScan Commercial database. Women were required to have 6 months of continuous coverage before (baseline) and 24 months after (follow-up) the procedure date. Women with ≥1 diagnosis for a pain condition (pain in pelvis/lower abdomen, low back pain, chronic headache, fibromyalgia) and/or AUB (excessive/frequent menstruation, irregular menstrual cycle, metorrhagia) during baseline were identified with International Classification of Diseases, Ninth Revision, Clinical Modification codes. HS/LS. Outcome measurements were proportions of women with CPP, AUB, and hysterectomy during follow-up. Among the study population 10 224 women underwent HS, whereas 8051 underwent LS. During baseline 23.3% and 26.9% of women with HS and LS, respectively, had a pre-existing pain diagnosis. Among both HS and LS study cohorts, greater proportions of women with a pre-existing pain condition versus those without had CPP in the 24 months afterward (HS cohort: 19.8% vs 9.3%, p < .001; LS cohort: 23.8% vs 11.4%, p < .001). During baseline 11.7% and 6.4% of women with HS and LS, respectively, had pre-existing AUB. Among cohorts, greater proportions of women with pre-existing AUB versus those without had AUB in the 24 months afterward (HS cohort: 21.2% vs 7.3%, p < .001; LS cohort: 15.9% vs 6.4%, p < .001). Among women who underwent HS and LS, pre-existing pain and AUB were associated with higher rates of hysterectomy postprocedure. Multivariable regression results showed similar direction of findings. Among women who underwent HS and LS, pre-existing pain conditions and AUB were associated with higher rates of CPP and AUB postprocedure, respectively, and both pre-existing conditions were associated with a greater frequency of subsequent hysterectomy. Copyright © 2017 American Association of Gynecologic Laparoscopists. Published by Elsevier Inc. All rights reserved.

Does help structures play a role in reducing the variation of dwell time in IPSA planning for gynaecological brachytherapy application?

PubMed Central

Mahantshetty, Umesh; Deshpande, DD; Sharma, Smriti; Shrivastava, SK

2011-01-01

Purpose To report our experience of dosimetric comparison of IPSA and manual plans, with a focus on the use of help structures (HS) during optimization. Material and methods 33 patients who underwent MR image-based HDR intracavitary-brachytherapy for cervix cancer based on GYN-ESTRO recommendations were selected for evaluation. Tandem/ovoid (T/O) and Vienna applicators were used. HS of diameter of 5 mm were drawn around the tandem/needles/ovoid and ring. Three plans were generated: manual optimized plan (MOPT), IPSA without help structures (IPSA_woHS) and IPSA with help structures (IPSA_wHS). Dose-volume parameters and the loading pattern were evaluated. Results For T/O, the use of HS did not make significant impact in the dose-volume parameters and in the loading of tandem and ovoids, however steep variation was found in the individual dwell time. In case of Vienna applicator, inclusion of HS in the optimization made a significant impact in loading of needles. The percentage ratio of total time of needles to the tandem (TN/T%) was found to be 14±2.5, 53±9, 22±6 for MOPT, IPSA_woHS and IPSA_wHS, respectively, which implies that in IPSA_woHS the dwell time in needles were half of the dwell time in the tandem, while in MOPT the needles were loaded only in 14%, and in IPSA_wHS it was 22% of the dwell time of tandem. Inclusion of HS in the optimization has reduced the contribution of dwell time of needle in IPSA_wHS. The individual variation of dwell time was also reduced in IPSA_wHS, however drawing of HS is a time consuming procedure and may not be practical for a routine practice. Conclusion The role of HS was evaluated for IPSA for T/O and Vienna-applicator, the use of HS may be beneficial in case of combined intracavitary – interstitial approach. PMID:23346124

Aqueous poly(amidoamine) dendrimer G3 and G4 generations with several interior cores at pHs 5 and 7: a molecular dynamics simulation study.

PubMed

Kavyani, Sajjad; Amjad-Iranagh, Sepideh; Modarress, Hamid

2014-03-27

Poly(amidoamine) (PAMAM) dendrimers play an important role in drug delivery systems, because the dendrimers are susceptible to gain unique features with modification of their structure such as changing their terminals or improving their interior core. To investigate the core improvement and the effect of core nature on PAMAM dendrimers, we studied two generations G3 and G4 PAMAM dendrimers with the interior cores of commonly used ethylendiamine (EDA), 1,5-diaminohexane (DAH), and bis(3-aminopropyl) ether (BAPE) solvated in water, as an aqueous dendrimer system, by using molecular dynamics simulation and applying a coarse-grained (CG) dendrimer force field. To consider the electrostatic interactions, the simulations were performed at two protonation states, pHs 5 and 7. The results indicated that the core improvement of PAMAM dendrimers with DAH produces the largest size for G3 and G4 dendrimers at both pHs 5 and 7. The increase in the size was also observed for BAPE core but it was not so significant as that for DAH core. By considering the internal structure of dendrimers, it was found that PAMAM dendrimer shell with DAH core had more cavities than with BAPE core at both pHs 5 and 7. Also the moment of inertia calculations showed that the generation G3 is more open-shaped and has higher structural asymmetry than the generation G4. Possessing these properties by G3, specially due to its structural asymmetry, make penetration of water beads into the dendrimer feasible. But for higher generation G4 with its relatively structural symmetry, the encapsulation efficiency for water molecules can be enhanced by changing its core to DAH or BAPE. It is also observed that for the higher generation G4 the effect of core modification is more profound than G3 because the core modification promotes the structural asymmetry development of G4 more significantly. Comparing the number of water beads that penetrate into the PAMAM dendrimers for EDA, DAH, and BAPE cores indicates a significant increase when their cores have been modified with DAH or BAPE and substantiates the effective influence of the core nature in the dendrimer encapsulation efficiency.

Dynamic Harmony Search with Polynomial Mutation Algorithm for Valve-Point Economic Load Dispatch

PubMed Central

Karthikeyan, M.; Sree Ranga Raja, T.

2015-01-01

Economic load dispatch (ELD) problem is an important issue in the operation and control of modern control system. The ELD problem is complex and nonlinear with equality and inequality constraints which makes it hard to be efficiently solved. This paper presents a new modification of harmony search (HS) algorithm named as dynamic harmony search with polynomial mutation (DHSPM) algorithm to solve ORPD problem. In DHSPM algorithm the key parameters of HS algorithm like harmony memory considering rate (HMCR) and pitch adjusting rate (PAR) are changed dynamically and there is no need to predefine these parameters. Additionally polynomial mutation is inserted in the updating step of HS algorithm to favor exploration and exploitation of the search space. The DHSPM algorithm is tested with three power system cases consisting of 3, 13, and 40 thermal units. The computational results show that the DHSPM algorithm is more effective in finding better solutions than other computational intelligence based methods. PMID:26491710

Dynamic Harmony Search with Polynomial Mutation Algorithm for Valve-Point Economic Load Dispatch.

PubMed

Karthikeyan, M; Raja, T Sree Ranga

2015-01-01

Economic load dispatch (ELD) problem is an important issue in the operation and control of modern control system. The ELD problem is complex and nonlinear with equality and inequality constraints which makes it hard to be efficiently solved. This paper presents a new modification of harmony search (HS) algorithm named as dynamic harmony search with polynomial mutation (DHSPM) algorithm to solve ORPD problem. In DHSPM algorithm the key parameters of HS algorithm like harmony memory considering rate (HMCR) and pitch adjusting rate (PAR) are changed dynamically and there is no need to predefine these parameters. Additionally polynomial mutation is inserted in the updating step of HS algorithm to favor exploration and exploitation of the search space. The DHSPM algorithm is tested with three power system cases consisting of 3, 13, and 40 thermal units. The computational results show that the DHSPM algorithm is more effective in finding better solutions than other computational intelligence based methods.

Identification and analysis of CYP450 genes from transcriptome of Lonicera japonica and expression analysis of chlorogenic acid biosynthesis related CYP450s.

PubMed

Qi, Xiwu; Yu, Xu; Xu, Daohua; Fang, Hailing; Dong, Ke; Li, Weilin; Liang, Chengyuan

2017-01-01

Lonicera japonica is an important medicinal plant that has been widely used in traditional Chinese medicine for thousands of years. The pharmacological activities of L. japonica are mainly due to its rich natural active ingredients, most of which are secondary metabolites. CYP450s are a large, complex, and widespread superfamily of proteins that participate in many endogenous and exogenous metabolic reactions, especially secondary metabolism. Here, we identified CYP450s in L. japonica transcriptome and analyzed CYP450s that may be involved in chlorogenic acid (CGA) biosynthesis. The recent availability of L. japonica transcriptome provided opportunity to identify CYP450s in this herb. BLAST based method and HMM based method were used to identify CYP450s in L. japonica transcriptome. Then, phylogenetic analysis, conserved motifs analysis, GO annotation, and KEGG annotation analyses were conducted to characterize the identified CYP450s. qRT-PCR was used to explore expression patterns of five CGA biosynthesis related CYP450s. In this study, 151 putative CYP450s with complete cytochrome P450 domain, which belonged to 10 clans, 45 families and 76 subfamilies, were identified in L. japonica transcriptome. Phylogenetic analysis classified these CYP450s into two major branches, A-type (47%) and non-A type (53%). Both types of CYP450s had conserved motifs in L. japonica . The differences of typical motif sequences between A-type and non-A type CYP450s in L. japonica were similar with other plants. GO classification indicated that non-A type CYP450s participated in more molecular functions and biological processes than A-type. KEGG pathway annotation totally assigned 47 CYP450s to 25 KEGG pathways. From these data, we cloned two LjC3Hs (CYP98A subfamily) and three LjC4Hs (CYP73A subfamily) that may be involved in biosynthesis of CGA, the major ingredient for pharmacological activities of L. japonica . qRT-PCR results indicated that two LjC3Hs exhibited oppositing expression patterns during the flower development and LjC3H2 exhibited a similar expression pattern with CGA concentration measured by HPLC. The expression patterns of three LjC4Hs were quite different and the expression pattern of LjC4H3 was quite similar with that of LjC3H1 . Our results provide a comprehensive identification and characterization of CYP450s in L. japonica . Five CGA biosynthesis related CYP450s were cloned and their expression patterns were explored. The different expression patterns of two LjC3Hs and three LjC4Hs may be due to functional divergence of both substrate and catalytic specificity during plant evolution. The co-expression pattern of LjC3H1 and LjC4H3 strongly suggested that they were under coordinated regulation by the same transcription factors due to same cis elements in their promoters. In conclusion, this study provides insight into CYP450s and will effectively facilitate the research of biosynthesis of CGA in L. japonica .

[Relationship of food groups intake and C-reactive protein in healthy adults from Mexicali, Baja California, México].

PubMed

Ruiz-Esparza, Josefina; Robinson-Navarro, Octavio; Ortega-Vélez, María Isabel; Diaz-Molina, Raúl; Carrillo-Cedillo, Eugenia Gabriela; Soria-Rodriguez, Carmen G

2013-09-01

The high sensitivity C-reactive protein (hs-CRP) is an important biomarker in inflammatory processes. The objective was to analyze the relationship between the concentrations of hs-CRP in adults from a northern Mexico region with their typical food intake patterns. A sample of 72 university professors underwent clinical and anthropometric assessments and their hs-CRP levels were quantified with an immunoenzymometric assay. Additionally, they filled out a food intake frequency questionnaire, from which the servings of different food groups were obtained with the ESHA software. The average age of participants was 49.75 +/- 10.05 years and the average hs-CRP concentration was 1.66 (0.97, 3.52) mg/L. The value of the association between fruit consumption and hs-CRP level was protective, according to the logistic regression analysis, being the Odds Ratio (OR) 0.23 (95% CI: 0.05, 1.03); while for vegetables the OR was 0.66 (95% CI: 0.12, 3.68). Furthermore, high protein content foods, dairy products, oils and fats were associated with elevated levels of hs-CRP. In conclusion, in our study, the intake of some food groups like fruits and vegetables, and to a lesser extent cereals, were associated with low values of hs-PCR.

Structure and epitope distribution of heparan sulfate is disrupted in experimental lung hypoplasia: a glycobiological epigenetic cause for malformation?

PubMed

Thompson, Sophie M; Connell, Marilyn G; van Kuppevelt, Toin H; Xu, Ruoyan; Turnbull, Jeremy E; Losty, Paul D; Fernig, David G; Jesudason, Edwin C

2011-06-14

Heparan sulfate (HS) is present on the surface of virtually all mammalian cells and is a major component of the extracellular matrix (ECM), where it plays a pivotal role in cell-cell and cell-matrix cross-talk through its large interactome. Disruption of HS biosynthesis in mice results in neonatal death as a consequence of malformed lungs, indicating that HS is crucial for airway morphogenesis. Neonatal mortality (~50%) in newborns with congenital diaphragmatic hernia (CDH) is principally associated with lung hypoplasia and pulmonary hypertension. Given the importance of HS for lung morphogenesis, we investigated developmental changes in HS structure in normal and hypoplastic lungs using the nitrofen rat model of CDH and semi-synthetic bacteriophage ('phage) display antibodies, which identify distinct HS structures. The pulmonary pattern of elaborated HS structures is developmentally regulated. For example, the HS4E4V epitope is highly expressed in sub-epithelial mesenchyme of E15.5 - E17.5 lungs and at a lower level in more distal mesenchyme. However, by E19.5, this epitope is expressed similarly throughout the lung mesenchyme.We also reveal abnormalities in HS fine structure and spatiotemporal distribution of HS epitopes in hypoplastic CDH lungs. These changes involve structures recognised by key growth factors, FGF2 and FGF9. For example, the EV3C3V epitope, which was abnormally distributed in the mesenchyme of hypoplastic lungs, is recognised by FGF2. The observed spatiotemporal changes in HS structure during normal lung development will likely reflect altered activities of many HS-binding proteins regulating lung morphogenesis. Abnormalities in HS structure and distribution in hypoplastic lungs can be expected to perturb HS:protein interactions, ECM microenvironments and crucial epithelial-mesenchyme communication, which may contribute to lung dysmorphogenesis. Indeed, a number of epitopes correlate with structures recognised by FGFs, suggesting a functional consequence of the observed changes in HS in these lungs. These results identify a novel, significant molecular defect in hypoplastic lungs and reveals HS as a potential contributor to hypoplastic lung development in CDH. Finally, these results afford the prospect that HS-mimetic therapeutics could repair defective signalling in hypoplastic lungs, improve lung growth, and reduce CDH mortality.

Structure and epitope distribution of heparan sulfate is disrupted in experimental lung hypoplasia: a glycobiological epigenetic cause for malformation?

PubMed Central

2011-01-01

Background Heparan sulfate (HS) is present on the surface of virtually all mammalian cells and is a major component of the extracellular matrix (ECM), where it plays a pivotal role in cell-cell and cell-matrix cross-talk through its large interactome. Disruption of HS biosynthesis in mice results in neonatal death as a consequence of malformed lungs, indicating that HS is crucial for airway morphogenesis. Neonatal mortality (~50%) in newborns with congenital diaphragmatic hernia (CDH) is principally associated with lung hypoplasia and pulmonary hypertension. Given the importance of HS for lung morphogenesis, we investigated developmental changes in HS structure in normal and hypoplastic lungs using the nitrofen rat model of CDH and semi-synthetic bacteriophage ('phage) display antibodies, which identify distinct HS structures. Results The pulmonary pattern of elaborated HS structures is developmentally regulated. For example, the HS4E4V epitope is highly expressed in sub-epithelial mesenchyme of E15.5 - E17.5 lungs and at a lower level in more distal mesenchyme. However, by E19.5, this epitope is expressed similarly throughout the lung mesenchyme. We also reveal abnormalities in HS fine structure and spatiotemporal distribution of HS epitopes in hypoplastic CDH lungs. These changes involve structures recognised by key growth factors, FGF2 and FGF9. For example, the EV3C3V epitope, which was abnormally distributed in the mesenchyme of hypoplastic lungs, is recognised by FGF2. Conclusions The observed spatiotemporal changes in HS structure during normal lung development will likely reflect altered activities of many HS-binding proteins regulating lung morphogenesis. Abnormalities in HS structure and distribution in hypoplastic lungs can be expected to perturb HS:protein interactions, ECM microenvironments and crucial epithelial-mesenchyme communication, which may contribute to lung dysmorphogenesis. Indeed, a number of epitopes correlate with structures recognised by FGFs, suggesting a functional consequence of the observed changes in HS in these lungs. These results identify a novel, significant molecular defect in hypoplastic lungs and reveals HS as a potential contributor to hypoplastic lung development in CDH. Finally, these results afford the prospect that HS-mimetic therapeutics could repair defective signalling in hypoplastic lungs, improve lung growth, and reduce CDH mortality. PMID:21672206

Health impact of fasting in Saudi Arabia during Ramadan: association with disturbed circadian rhythm and metabolic and sleeping patterns.

PubMed

Ajabnoor, Ghada M; Bahijri, Suhad; Borai, Anwar; Abdulkhaliq, Altaf A; Al-Aama, Jumana Y; Chrousos, George P

2014-01-01

Muslims go through strict Ramadan fasting from dawn till sunset for one month yearly. These practices are associated with disturbed feeding and sleep patterns. We recently demonstrated that, during Ramadan, circadian cortisol rhythm of Saudis is abolished, exposing these subjects to continuously increased cortisol levels. Secretory patterns of other hormones and metabolic parameters associated with cortisol, and insulin resistance, might be affected during Ramadan. Ramadan practitioners (18 males, 5 females; mean age ±SEM = 23.16±1.2 years) were evaluated before and two weeks into Ramadan. Blood was collected for measurements of endocrine and metabolic parameters at 9 am (±1 hour) and again twelve hours later. In Ramadan, glucose concentration was kept within normal range, with a significant increase in the morning. Mean morning concentration of leptin was significantly higher than pre-Ramadan values (p = 0.001), in contrast to that of adiponectin, which was significantly lower (p<0.001). These changes were associated with increased insulin resistance in morning and evening. Concentrations of hsCRP were lower during Ramadan than those during regular living conditions, however, normal circadian fluctuation was abolished (p = 0.49). Even though means of liver enzymes, total bilirubin, total protein and albumin were all decreased during Ramadan, statistically lower means were only noted for GGT, total protein, and albumin (p = 0.018, 0.002 and 0.001 respectively). Saudi Ramadan practitioners have altered adipokine patterns, typical of insulin resistance. The noted decreases of hsCRP, liver enzymes, total protein, and albumin, are most likely a result of fasting, while loss of circadian rhythmicity of hsCRP is probably due to loss of circadian cortisol rhythm. Modern Ramadan practices in Saudi Arabia, which are associated with evening hypercortisolism, are also characterized by altered adipokines patterns, and an abolished hsCRP circadian rhythm, all likely to increase cardiometabolic risk.

Novel Synthetic, Host-defense Peptide Protects Against Organ Injury/Dysfunction in a Rat Model of Severe Hemorrhagic Shock.

PubMed

Yamada, Noriaki; Martin, Lukas B; Zechendorf, Elisabeth; Purvis, Gareth S D; Chiazza, Fausto; Varrone, Barbara; Collino, Massimo; Shepherd, Joanna; Heinbockel, Lena; Gutsmann, Thomas; Correa, Wilmar; Brandenburg, Klaus; Marx, Gernot; Schuerholz, Tobias; Brohi, Karim; Thiemermann, Christoph

2017-03-10

To evaluate (1) levels of the host-defense/antimicrobial peptide LL-37 in patients with trauma and hemorrhagic shock (HS) and (2) the effects of a synthetic host-defense peptide; Pep19-4LF on multiple organ failure (MOF) associated with HS. HS is a common cause of death in severely injured patients. There is no specific therapy that reduces HS-associated MOF. (1) LL-37 was measured in 47 trauma/HS patients admitted to an urban major trauma center. (2) Male Wistar rats were submitted to HS (90 min, target mean arterial pressure: 27-32 mm Hg) or sham operation. Rats were treated with Pep19-4LF [66 (n = 8) or 333 μg/kg · h (n = 8)] or vehicle (n = 12) for 4 hours following resuscitation. Plasma LL-37 was 12-fold higher in patients with trauma/HS compared to healthy volunteers. HS rats treated with Pep19-4LF (high dose) had a higher mean arterial pressure at the end of the 4-hour resuscitation period (79 ± 4 vs 54 ± 5 mm Hg) and less renal dysfunction, liver injury, and lung inflammation than HS rats treated with vehicle. Pep19-4LF enhanced (kidney/liver) the phosphorylation of (1) protein kinase B and (2) endothelial nitric oxide synthase. Pep19-4LF attenuated the HS-induced (1) translocation of p65 from cytosol to nucleus, (2) phosphorylation of IκB kinase on Ser, and (3) phosphorylation of IκBα on Ser resulting in inhibition of nuclear factor kappa B and formation of proinflammatory cytokines. Pep19-4LF prevented the release of tumor necrosis factor alpha caused by heparan sulfate in human mononuclear cells by binding to this damage-associated molecular pattern. Trauma-associated HS results in release of LL-37. The synthetic host-defense/antimicrobial peptide Pep19-4LF attenuates the organ injury/dysfunction associated with HS.

Application of spatially modulated near-infrared structured light to study changes in optical properties of mouse brain tissue during heatstress.

PubMed

Shaul, Oren; Fanrazi-Kahana, Michal; Meitav, Omri; Pinhasi, Gad A; Abookasis, David

2017-11-10

Heat stress (HS) is a medical emergency defined by abnormally elevated body temperature that causes biochemical, physiological, and hematological changes. The goal of the present research was to detect variations in optical properties (absorption, reduced scattering, and refractive index coefficients) of mouse brain tissue during HS by using near-infrared (NIR) spatial light modulation. NIR spatial patterns with different spatial phases were used to differentiate the effects of tissue scattering from those of absorption. Decoupling optical scattering from absorption enabled the quantification of a tissue's chemical constituents (related to light absorption) and structural properties (related to light scattering). Technically, structured light patterns at low and high spatial frequencies of six wavelengths ranging between 690 and 970 nm were projected onto the mouse scalp surface while diffuse reflected light was recorded by a CCD camera positioned perpendicular to the mouse scalp. Concurrently to pattern projection, brain temperature was measured with a thermal camera positioned slightly off angle from the mouse head while core body temperature was monitored by thermocouple probe. Data analysis demonstrated variations from baseline measurements in a battery of intrinsic brain properties following HS.

The Ndst Gene Family in Zebrafish: Role of Ndst1b in Pharyngeal Arch Formation

PubMed Central

Haitina, Tatjana; Habicher, Judith; Ledin, Johan; Kjellén, Lena

2015-01-01

Heparan sulfate (HS) proteoglycans are ubiquitous components of the extracellular matrix and plasma membrane of metazoans. The sulfation pattern of the HS glycosaminoglycan chain is characteristic for each tissue and changes during development. The glucosaminyl N-deacetylase/N-sulfotransferase (NDST) enzymes catalyze N-deacetylation and N-sulfation during HS biosynthesis and have a key role in designing the sulfation pattern. We here report on the presence of five NDST genes in zebrafish. Zebrafish ndst1a, ndst1b, ndst2a and ndst2b represent duplicated mammalian orthologues of NDST1 and NDST2 that arose through teleost specific genome duplication. Interestingly, the single zebrafish orthologue ndst3, is equally similar to tetrapod Ndst3 and Ndst4. It is likely that a local duplication in the common ancestor of lobe-finned fish and tetrapods gave rise to these two genes. All zebrafish Ndst genes showed distinct but partially overlapping expression patterns during embryonic development. Morpholino knockdown of ndst1b resulted in delayed development, craniofacial cartilage abnormalities, shortened body and pectoral fin length, resembling some of the features of the Ndst1 mouse knockout. PMID:25767878

Gas-Phase Analysis of the Complex of Fibroblast GrowthFactor 1 with Heparan Sulfate: A Traveling Wave Ion Mobility Spectrometry (TWIMS) and Molecular Modeling Study

NASA Astrophysics Data System (ADS)

Zhao, Yuejie; Singh, Arunima; Xu, Yongmei; Zong, Chengli; Zhang, Fuming; Boons, Geert-Jan; Liu, Jian; Linhardt, Robert J.; Woods, Robert J.; Amster, I. Jonathan

2017-01-01

Fibroblast growth factors (FGFs) regulate several cellular developmental processes by interacting with cell surface heparan proteoglycans and transmembrane cell surface receptors (FGFR). The interaction of FGF with heparan sulfate (HS) is known to induce protein oligomerization, increase the affinity of FGF towards its receptor FGFR, promoting the formation of the HS-FGF-FGFR signaling complex. Although the role of HS in the signaling pathways is well recognized, the details of FGF oligomerization and formation of the ternary signaling complex are still not clear, with several conflicting models proposed in literature. Here, we examine the effect of size and sulfation pattern of HS upon FGF1 oligomerization, binding stoichiometry and conformational stability, through a combination of ion mobility (IM) and theoretical modeling approaches. Ion mobility-mass spectrometry (IMMS) of FGF1 in the presence of several HS fragments ranging from tetrasaccharide (dp4) to dodecasaccharide (dp12) in length was performed. A comparison of the binding stoichiometry of variably sulfated dp4 HS to FGF1 confirmed the significance of the previously known high-affinity binding motif in FGF1 dimerization, and demonstrated that certain tetrasaccharide-length fragments are also capable of inducing dimerization of FGF1. The degree of oligomerization was found to increase in the presence of dp12 HS, and a general lack of specificity for longer HS was observed. Additionally, collision cross-sections (CCSs) of several FGF1-HS complexes were calculated, and were found to be in close agreement with experimental results. Based on the (CCSs) a number of plausible binding modes of 2:1 and 3:1 FGF1-HS are proposed.

A Network of HSPG Core Proteins and HS Modifying Enzymes Regulates Netrin-Dependent Guidance of D-Type Motor Neurons in Caenorhabditis elegans

PubMed Central

Gysi, Stephan; Rhiner, Christa; Flibotte, Stephane; Moerman, Donald G.; Hengartner, Michael O.

2013-01-01

Heparan sulfate proteoglycans (HSPGs) are proteins with long covalently attached sugar side chains of the heparan sulfate (HS) type. Depending on the cellular context HS chains carry multiple structural modifications such as sulfate residues or epimerized sugars allowing them to bind to a wide range of molecules. HSPGs have been found to play extremely diverse roles in animal development and were shown to interact with certain axon guidance molecules. In this study we describe the role of the Caenorhabditis elegans HSPG core proteins Syndecan (SDN-1) and Glypican (LON-2) and the HS modifying enzymes in the dorsal guidance of D-type motor axons, a process controlled mainly by the conserved axon guidance molecule UNC-6/Netrin. Our genetic analysis established the specific HS code relevant for this axon guidance event. Using two sensitized genetic backgrounds, we isolated novel components influencing D-type motor axon guidance with a link to HSPGs, as well as new alleles of several previously characterized axon guidance genes. Interestingly, the dorsal axon guidance defects induced by mutations in zfp-1 or lin-35 depended on the transgene oxIs12 used to visualize the D-type motor neurons. oxIs12 is a large multi-copy transgene that enlarges the X chromosome by approximately 20%. In a search for genes with a comparable phenotype we found that a mutation in the known dosage compensation gene dpy-21 showed similar axon guidance defects as zfp-1 or lin-35 mutants. Thus, derepression of genes on X, where many genes relevant for HS dependent axon guidance are located, might also influence axon guidance of D-type motor neurons. PMID:24066155

Binding affinities of vascular endothelial growth factor (VEGF) for heparin-derived oligosaccharides

PubMed Central

Zhao, Wenjing; McCallum, Scott A.; Xiao, Zhongping; Zhang, Fuming; Linhardt, Robert J.

2011-01-01

Heparin and heparan sulphate (HS) exert their wide range of biological activities by interacting with extracellular protein ligands. Among these important protein ligands are various angiogenic growth factors and cytokines. HS-binding to vascular endothelial growth factor (VEGF) regulates multiple aspects of vascular development and function through its specific interaction with HS. Many studies have focused on HS-derived or HS-mimicking structures for the characterization of VEGF165 interaction with HS. Using a heparinase 1-prepared small library of heparin-derived oligosaccharides ranging from hexasaccharide to octadecasaccharide, we systematically investigated the heparin-specific structural features required for VEGF binding. We report the apparent affinities for the association between the heparin-derived oligosaccharides with both VEGF165 and VEGF55, a peptide construct encompassing exclusively the heparin-binding domain of VEGF165. An octasaccharide was the minimum size of oligosaccharide within the library to efficiently bind to both forms of VEGF and that a tetradecasaccharide displayed an effective binding affinity to VEGF165 comparable to unfractionated heparin. The range of relative apparent binding affinities among VEGF and the panel of heparin-derived oligosaccharides demonstrate that VEGF binding affinity likely depends on the specific structural features of these oligosaccharides including their degree of sulphation and sugar ring stereochemistry and conformation. Notably, the unique 3-O-sulpho group found within the specific antithrombin binding site of heparin is not required for VEGF165 binding. These findings afford new insight into the inherent kinetics and affinities for VEGF association with heparin and heparin-derived oligosaccharides with key residue specific modifications and may potentially benefit the future design of oligosaccharide-based anti-angiogenesis drugs. PMID:21658003

Multimodal approach to characterization of hydrophilic matrices manufactured by wet and dry granulation or direct compression methods.

PubMed

Kulinowski, Piotr; Woyna-Orlewicz, Krzysztof; Obrał, Jadwiga; Rappen, Gerd-Martin; Haznar-Garbacz, Dorota; Węglarz, Władysław P; Jachowicz, Renata; Wyszogrodzka, Gabriela; Klaja, Jolanta; Dorożyński, Przemysław P

2016-02-29

The purpose of the research was to investigate the effect of the manufacturing process of the controlled release hydrophilic matrix tablets on their hydration behavior, internal structure and drug release. Direct compression (DC) quetiapine hemifumarate matrices and matrices made of powders obtained by dry granulation (DG) and high shear wet granulation (HS) were prepared. They had the same quantitative composition and they were evaluated using X-ray microtomography, magnetic resonance imaging and biorelevant stress test dissolution. Principal results concerned matrices after 2 h of hydration: (i) layered structure of the DC and DG hydrated tablets with magnetic resonance image intensity decreasing towards the center of the matrix was observed, while in HS matrices layer of lower intensity appeared in the middle of hydrated part; (ii) the DC and DG tablets retained their core and consequently exhibited higher resistance to the physiological stresses during simulation of small intestinal passage than HS formulation. Comparing to DC, HS granulation changed properties of the matrix in terms of hydration pattern and resistance to stress in biorelevant dissolution apparatus. Dry granulation did not change these properties-similar hydration pattern and dissolution in biorelevant conditions were observed for DC and DG matrices. Copyright © 2015 Elsevier B.V. All rights reserved.

Pollen grain morphology of Fabaceae in the Special Protection Area (SPA) Pau-de-Fruta, Diamantina, Minas Gerais, Brazil.

PubMed

Luz, Cynthia F P da; Maki, Erica S; Horák-Terra, Ingrid; Vidal-Torrado, Pablo; Mendonça Filho, Carlos Victor

2013-01-01

The presented paper considered the pollen morphology of thirteen species belonging to seven genera of the Fabaceae family occurring in the Pau-de-Fruta Special Protection Area (SPA), Diamantina, state of Minas Gerais, Brazil. The pollen grains of six species of Chamaecrista [C. cathartica (Mart.) H.S. Irwin & Barneby, C. debilis Vogel, C. flexuosa (L.) Greene, C. hedysaroides (Vogel) H.S. Irwin & Barneby, C. glandulosa (L.) Greene, and C. papillata H.S. Irwin & Barneby] have a similar morphology, characterized by three long colporated apertures with a central constriction. The species share specific morphological features regarding pollen size, endoaperture type (circular, lalongate or lolongate) and SEM ornamentation patterns of the exine (rugulate with perforations or perforate). Andira fraxinifolia Benth., Dalbergia miscolobium Benth, Galactia martii DC, Periandra mediterranea (Vell.) Taub., Senna rugosa (G.Don) H.S. Irwin & Barneby and Zornia diphylla (L.) Pers showed different pollen types in small to large size; oblate spheroidal to prolate form; colpus or colporus apertures; circular, lalongate or lolongate endoapertures and distinctive SEM ornamentation patterns of the exine (perforate, microreticulate, reticulate or rugulate with perforations). Only Stryphnodendron adstringens (Mart.) Coville presents polyads. The pollen morphology variation of these species allowed the Fabaceae family to be characterized as eurypalynous in the SPA Pau-de-Fruta.

DASH diet, insulin resistance, and serum hs-CRP in polycystic ovary syndrome: a randomized controlled clinical trial.

PubMed

Asemi, Z; Esmaillzadeh, A

2015-03-01

This study was designed to assess the effects of Dietary Approaches to Stop Hypertension (DASH) eating plan on insulin resistance and serum hs-CRP in overweight and obese women with PCOS. This randomized controlled clinical trial was done on 48 women diagnosed with PCOS. Subjects were randomly assigned to consume either the control (n=24) or the DASH eating pattern (n=24) for 8 weeks. The DASH diet consisted of 52% carbohydrates, 18% proteins, and 30% total fats. It was designed to be rich in fruits, vegetables, whole grains, and low-fat dairy products and low in saturated fats, cholesterol, refined grains, and sweets. Sodium content of the DASH diet was designed to be less than 2 400 mg/day. The control diet was also designed to contain 52% carbohydrates, 18% protein, and 30% total fat. Fasting blood samples were taken at baseline and after 8 weeks intervention to measure -insulin resistance and serum hs-CRP levels. -Adherence to the DASH eating pattern, compared to the -control diet, resulted in a significant reduction of serum insulin levels (-1.88 vs. 2.89 μIU/ml, p=0.03), HOMA-IR score (-0.45 vs. 0.80; p=0.01), and serum hs-CRP levels (-763.29 vs. 665.95 ng/ml, p=0.009). Additionally, a significant reduction in waist (-5.2 vs. -2.1 cm; p=0.003) and hip circumference (-5.9 vs. -1 cm; p<0.0001) was also seen in the DASH group compared with the control group. In conclusion, consumption of the DASH eating pattern for 8 weeks in overweight and obese women with PCOS resulted in the improvement of insulin resistance, serum hs-CRP levels, and abdominal fat accumulation. www.irct.ir: IRCT201304235623N6. © Georg Thieme Verlag KG Stuttgart · New York.

Development of an activity-based probe for acyl-protein thioesterases

PubMed Central

Garland, Megan; Schulze, Christopher J.; Foe, Ian T.; van der Linden, Wouter A.; Child, Matthew A.

2018-01-01

Protein palmitoylation is a dynamic post-translational modification (PTM) important for cellular functions such as protein stability, trafficking, localization, and protein-protein interactions. S-palmitoylation occurs via the addition of palmitate to cysteine residues via a thioester linkage, catalyzed by palmitoyl acyl transferases (PATs), with removal of the palmitate catalyzed by acyl protein thioesterases (APTs) and palmitoyl-protein thioesterases (PPTs). Tools that target the regulators of palmitoylation–PATs, APTs and PPTs–will improve understanding of this essential PTM. Here, we describe the synthesis and application of a cell-permeable activity-based probe (ABP) that targets APTs in intact mammalian cells and the parasite Toxoplasma gondii. Using a focused library of substituted chloroisocoumarins, we identified a probe scaffold with nanomolar affinity for human APTs (HsAPT1 and HsAPT2) and synthesized a fluorescent ABP, JCP174-BODIPY TMR (JCP174-BT). We use JCP174-BT to profile HsAPT activity in situ in mammalian cells, to detect an APT in T. gondii (TgPPT1). We show discordance between HsAPT activity levels and total protein concentration in some cell lines, indicating that total protein levels may not be representative of APT activity in complex systems, highlighting the utility of this probe. PMID:29364904

Participation of 3-O-sulfated heparan sulfates in the protection of macrophages by herpes simplex virus-1 glycoprotein D and cyclophilin B against apoptosis.

PubMed

Delos, Maxime; Hellec, Charles; Foulquier, François; Carpentier, Mathieu; Allain, Fabrice; Denys, Agnès

2017-02-01

Heparan sulfates (HS) are involved in numerous biological processes, which rely on their ability to interact with a large panel of proteins. Although the reaction of 3-O-sulfation can be catalysed by the largest family of HS sulfotransferases, very few mechanisms have been associated with this modification and to date, only glycoprotein D (gD) of herpes simplex virus-1 (HSV-1 gD) and cyclophilin B (CyPB) have been well-described as ligands for 3- O -sulfated HS. Here, we hypothesized that both ligands could induce the same responses via a mechanism dependent on 3- O -sulfated HS. First, we checked that HSV-1 gD was as efficient as CyPB to induce the activation of the same signalling events in primary macrophages. We then demonstrated that both ligands efficiently reduced staurosporin-induced apoptosis and modulated the expression of apoptotic genes. In addition to 3- O -sulfated HS, HSV-1 gD was reported to interact with other receptors, including herpes virus entry mediator (HVEM), nectin-1 and -2. Thus, we decided to identify the contribution of each binding site in the responses triggered by HSV-1 gD and CyPB. We found that knock-down of 3- O -sulfotransferase 2, which is the main 3- O -sulfated HS-generating enzyme in macrophages, strongly reduced the responses induced by both ligands. Moreover, silencing the expression of HVEM rendered macrophages unresponsive to either HSV-1 gD and CyPB, thus indicating that both proteins induced the same responses by interacting with a complex formed by 3- O -sulfated HS and HVEM. Collectively, our results suggest that HSV-1 might hijack the binding sites for CyPB in order to protect macrophages against apoptosis for efficient infection.

Concentrative nitrogen allocation to sun-lit branches and the effects on whole-plant growth under heterogeneous light environments.

PubMed

Sugiura, D; Tateno, M

2013-08-01

We investigated the nitrogen and carbohydrate allocation patterns of trees under heterogeneous light environments using saplings of the devil maple tree (Acer diabolicum) with Y-shaped branches. Different branch groups were created: all branches of a sapling exposed to full light (L-branches), all branches exposed to full shade (S-branches), and half of the branches of a sapling exposed to light (HL-branches) and the other half exposed to shade (HS-branches). Throughout the growth period, nitrogen was preferentially allocated to HL-branches, whereas nitrogen allocation to HS-branches was suppressed compared to L- and S-branches. HL-branches with the highest leaf nitrogen content (N(area)) also had the highest rates of growth, and HS-branches with the lowest N(area) had the lowest observed growth rates. In addition, net nitrogen assimilation, estimated using a photosynthesis model, was strongly correlated with branch growth and whole-plant growth. In contrast, patterns of photosynthate allocation to branches and roots were not affected by the light conditions of the other branch. These observations suggest that tree canopies develop as a result of resource allocation patterns, where the growth of sun-lit branches is favoured over shaded branches, which leads to enhanced whole-plant growth in heterogeneous light environments. Our results indicate that whole-plant growth is enhanced by the resource allocation patterns created for saplings in heterogeneous light environments.

Neocortical temporal FDG-PET hypometabolism correlates with temporal lobe atrophy in hippocampal sclerosis associated with microscopic cortical dysplasia.

PubMed

Diehl, Beate; LaPresto, Eric; Najm, Imad; Raja, Shanker; Rona, Sabine; Babb, Thomas; Ying, Zhong; Bingaman, William; Lüders, Hans O; Ruggieri, Paul

2003-04-01

Medically intractable temporal lobe epilepsy (TLE) due to hippocampal sclerosis (HS), with or without cortical dysplasia (CD), is associated with atrophy of the hippocampal formation and regional fluorodeoxyglucose positron-emission tomography (FDG-PET) hypometabolism. The relation between areas of functional and structural abnormalities is not well understood. We investigate the relation between FDG-PET metabolism and temporal lobe (TL) and hippocampal atrophy in patients with histologically proven isolated HS and HS associated with CD. Twenty-three patients underwent en bloc resection of the mesial and anterolateral neocortical structures. Ten patients were diagnosed with isolated HS; 13 patients had associated microscopic CD. Temporal lobe volumes (TLVs) and hippocampal volumes were measured. Magnetic resonance imaging (MRI) and PET were co-registered, and regions of interest (ROIs) determined as gray matter of the mesial, lateral, and anterior temporal lobe. All patients (HS with or without CD) had significant ipsilateral PET hypometabolism in all three regions studied (p < 0.0001). In patients with isolated HS, the most prominent hypometabolism was in the anterior and mesial temporal lobe, whereas in dual pathology, it was in the lateral temporal lobe. TLVs and hippocampal volumes were significantly smaller on the epileptogenic side (p < 0.05). The PET asymmetries ipsilateral/contralateral to the epileptogenic zone and TLV asymmetries correlated significantly for the anterior and lateral temporal lobes (p < 0.05) in the HS+CD group, but not in the isolated HS group. Mesial temporal hypometabolism was not significantly different between the two groups. Temporal neocortical microscopic CD with concurrent HS is associated with more prominent lateral temporal metabolic dysfunction compared with isolated HS in TL atrophy. Further studies are needed to confirm these findings and correlate the PET hypometabolic patterns with outcome data in patients operated on for HS with or without CD.

Abnormalities of hippocampal-cortical connectivity in temporal lobe epilepsy patients with hippocampal sclerosis

NASA Astrophysics Data System (ADS)

Li, Wenjing; He, Huiguang; Lu, Jingjing; Wang, Chunheng; Li, Meng; Lv, Bin; Jin, Zhengyu

2011-03-01

Hippocampal sclerosis (HS) is the most common damage seen in the patients with temporal lobe epilepsy (TLE). In the present study, the hippocampal-cortical connectivity was defined as the correlation between the hippocampal volume and cortical thickness at each vertex throughout the whole brain. We aimed to investigate the differences of ipsilateral hippocampal-cortical connectivity between the unilateral TLE-HS patients and the normal controls. In our study, the bilateral hippocampal volumes were first measured in each subject, and we found that the ipsilateral hippocampal volume significantly decreased in the left TLE-HS patients. Then, group analysis showed significant thinner average cortical thickness of the whole brain in the left TLE-HS patients compared with the normal controls. We found significantly increased ipsilateral hippocampal-cortical connectivity in the bilateral superior temporal gyrus, the right cingulate gyrus and the left parahippocampal gyrus of the left TLE-HS patients, which indicated structural vulnerability related to the hippocampus atrophy in the patient group. However, for the right TLE-HS patients, no significant differences were found between the patients and the normal controls, regardless of the ipsilateral hippocampal volume, the average cortical thickness or the patterns of hippocampal-cortical connectivity, which might be related to less atrophies observed in the MRI scans. Our study provided more evidence for the structural abnormalities in the unilateral TLE-HS patients.

Jump-Squat and Half-Squat Exercises: Selective Influences on Speed-Power Performance of Elite Rugby Sevens Players

PubMed Central

Loturco, Irineu; Pereira, Lucas A.; Moraes, José E.; Kitamura, Katia; Cal Abad, César C.; Kobal, Ronaldo; Nakamura, Fábio Y.

2017-01-01

The aim of this study was to evaluate the relation between the maximum mean propulsive power (MPP) obtained in the loaded jump squat (JS) and half squat (HS) exercises and functional performances in vertical jumps, 40 m linear speed (VEL) and change-of-direction (COD) tests, using the median split technique. Twenty-two male rugby sevens players from the Brazilian National Olympic Team (Rio-2016) performed vertical jumping tests (squat and countermovement jumps [SJ and CMJ]), JS and HS exercises, COD speed test and sprinting velocity in 40 m, in this order. Based on the results of the MPP in the JS and HS exercises the participants were divided, using the median split, into four groups as follows: higher JS, lower JS, higher HS, and lower HS. Between-group differences in the functional tasks were detected via magnitude-based inferences. The athletes with higher MPP in the JS were capable of jumping higher and sprinting faster (including the COD speed test) than their weaker counterparts. This pattern was not observed in the HS exercise. To conclude, JS was shown to be more connected to sprinting, COD speed and jumping abilities than HS in elite rugby sevens players and should be preferred for assessing and possibly training elite athletes needing to improve speed-power related abilities. PMID:28114431

Jump-Squat and Half-Squat Exercises: Selective Influences on Speed-Power Performance of Elite Rugby Sevens Players.

PubMed

Loturco, Irineu; Pereira, Lucas A; Moraes, José E; Kitamura, Katia; Cal Abad, César C; Kobal, Ronaldo; Nakamura, Fábio Y

2017-01-01

The aim of this study was to evaluate the relation between the maximum mean propulsive power (MPP) obtained in the loaded jump squat (JS) and half squat (HS) exercises and functional performances in vertical jumps, 40 m linear speed (VEL) and change-of-direction (COD) tests, using the median split technique. Twenty-two male rugby sevens players from the Brazilian National Olympic Team (Rio-2016) performed vertical jumping tests (squat and countermovement jumps [SJ and CMJ]), JS and HS exercises, COD speed test and sprinting velocity in 40 m, in this order. Based on the results of the MPP in the JS and HS exercises the participants were divided, using the median split, into four groups as follows: higher JS, lower JS, higher HS, and lower HS. Between-group differences in the functional tasks were detected via magnitude-based inferences. The athletes with higher MPP in the JS were capable of jumping higher and sprinting faster (including the COD speed test) than their weaker counterparts. This pattern was not observed in the HS exercise. To conclude, JS was shown to be more connected to sprinting, COD speed and jumping abilities than HS in elite rugby sevens players and should be preferred for assessing and possibly training elite athletes needing to improve speed-power related abilities.

Functional genomics of commercial baker's yeasts that have different abilities for sugar utilization and high-sucrose tolerance under different sugar conditions.

PubMed

Tanaka-Tsuno, Fumiko; Mizukami-Murata, Satomi; Murata, Yoshinori; Nakamura, Toshihide; Ando, Akira; Takagi, Hiroshi; Shima, Jun

2007-10-01

In the modern baking industry, high-sucrose-tolerant (HS) and maltose-utilizing (LS) yeast were developed using breeding techniques and are now used commercially. Sugar utilization and high-sucrose tolerance differ significantly between HS and LS yeasts. We analysed the gene expression profiles of HS and LS yeasts under different sucrose conditions in order to determine their basic physiology. Two-way hierarchical clustering was performed to obtain the overall patterns of gene expression. The clustering clearly showed that the gene expression patterns of LS yeast differed from those of HS yeast. Quality threshold clustering was used to identify the gene clusters containing upregulated genes (cluster 1) and downregulated genes (cluster 2) under high-sucrose conditions. Clusters 1 and 2 contained numerous genes involved in carbon and nitrogen metabolism, respectively. The expression level of the genes involved in the metabolism of glycerol and trehalose, which are known to be osmoprotectants, in LS yeast was higher than that in HS yeast under sucrose concentrations of 5-40%. No clear correlation was found between the expression level of the genes involved in the biosynthesis of the osmoprotectants and the intracellular contents of the osmoprotectants. The present gene expression data were compared with data previously reported in a comprehensive analysis of a gene deletion strain collection. Welch's t-test for this comparison showed that the relative growth rates of the deletion strains whose deletion occurred in genes belonging to cluster 1 were significantly higher than the average growth rates of all deletion strains. Copyright 2007 John Wiley & Sons, Ltd.

Utilization Patterns of Lipid-lowering Therapies in Patients With Atherosclerotic Cardiovascular Disease or Diabetes: A Population-based Study in South Korea.

PubMed

Kim, Siin; Kim, Hyungtae; Kim, Eunju; Han, Sola; Rane, Pratik P; Fox, Kathleen M; Zhao, Zhongyun; Qian, Yi; Suh, Hae Sun

2018-06-01

We aimed to study the utilization patterns of lipid-lowering treatment (LLT), including treatment modification, adherence, and possible statin intolerance, in patients with atherosclerotic cardiovascular disease (ASCVD) or diabetes using national claims data in South Korea. A retrospective cohort study was conducted using data from the Korean Health Insurance Review & Assessment Service claims database. Patients aged ≥18 years with >1 outpatient pharmacy claim for a statin and/or ezetimibe dated January 1, 2012, to December 31, 2014, were identified and categorized into the following cohorts: patients with ASCVD, and patients with diabetes mellitus without ASCVD. LLT modification, adherence to index LLT, and possible statin intolerance were explored during the 12 months after the date of first prescription for a statin and/or ezetimibe. Among 1,399,872 patients who met the eligibility criteria, 807,547 (57.7%) were patients with ASCVD and 592,325 (42.3%) were patients with diabetes without ASCVD. About half of the patients had no modification in their index treatment (46.2% in the ASCVD cohort and 48.9% in the diabetes cohort), and the most common modification was permanent discontinuation (19.6% in the ASCVD cohort and 21.4% in the diabetes cohort). The mean medication possession ratios were 0.77 in the ASCVD cohort and 0.73 in the diabetes cohort and showed a decreasing trend during the 12-month follow-up period. Among patients who initiated a statin and/or ezetimibe, possible statin intolerance was observed in 53,921 patients (6.7%) in the ASCVD cohort and 42,172 patients (7.1%) in the diabetes cohort. In South Korea, a high rate of permanent discontinuation of statin therapy in patients with ASCVD or diabetes places these patients at high risk for cardiovascular events in the future. A decreasing trend of adherence to LLT implies that more intensive education and management are required to improve therapeutic effect and reduce the risk for ASCVD. The high rate of possible statin intolerance highlights an unmet need in the prevention and management of ASCVD in South Korea. Copyright © 2018 Elsevier HS Journals, Inc. All rights reserved.

Granulocyte colony-stimulating factor (G-CSF) production in hemorrhagic shock requires both the ischemic and resuscitation phase.

PubMed

Hierholzer, C; Kelly, E; Billiar, T R; Tweardy, D J

1997-01-01

Granulocyte colony-stimulating factor (G-CSF) is the cytokine that is critical for polymorphonuclear neutrophilic granulocyte (PMN) production as well as being a potent agonist of PMN activation. We have recently reported that in the lung and the liver of rats resuscitated after hemorrhagic shock (HS) G-CSF mRNA expression is induced. It is not known if both phases of HS, the ischemic and the reperfusion phase, are required for G-CSF mRNA induction. The present study was designed to test the hypothesis that the upregulation of G-CSF mRNA expression is the consequence of HS followed by resuscitation and that ischemia alone is insufficient to induce G-CSF mRNA expression in the affected organs. Male Sprague-Dawley rats were subjected to resuscitated and unresuscitated shock protocols of varying severity. Control animals were subjected to anesthesia and all surgical preparations except for hemorrhage. Lungs and livers were isolated and their RNA extracted. Using semiquantitative reverse transcriptase-polymerase chain reaction (RT-PCR), we demonstrated that G-CSF mRNA was induced in the lung and liver of shock animals above the level observed in control animals. Upregulation of G-CSF mRNA relative to controls occurred only in animals undergoing resuscitated HS and not in ones subjected to unresuscitated HS. These results indicate that G-CSF production specific for the hemorrhage component of shock is dependent on resuscitation. As a consequence, the production of this cytokine may be decreased through modifications in the resuscitation protocols.

The Learning and Study Strategies Inventory-High School Version: Issues of Factorial Invariance Across Gender and Ethnicity

ERIC Educational Resources Information Center

Stevens, Tara; Tallent-Runnels, Mary K.

2004-01-01

The purpose of this study was to investigate the latent structure of the Learning and Study Strategies Inventory-High School (LASSI-HS) through confirmatory factor analysis and factorial invariance models. A simple modification of the three-factor structure was considered. Using a larger sample, cross-validation was completed and the equality of…

Metabolic engineering of Chinese hamster ovary cells: Towards a bioengineered heparin

PubMed Central

Baik, Jong Youn; Gasimli, Leyla; Yang, Bo; Datta, Payel; Zhang, Fuming; Glass, Charles A.; Esko, Jeffrey D.; Linhardt, Robert J.; Sharfstein, Susan T.

2012-01-01

Heparin is the most widely used pharmaceutical to control blood coagulation in modern medicine. A health crisis that took place in 2008 led to a demand for production of heparin from non-animal sources. Chinese hamster ovary (CHO) cells, commonly used mammalian host cells for production of foreign pharmaceutical proteins in the biopharmaceutical industry, are capable of producing heparan sulfate (HS), a related polysaccharide naturally. Since heparin and HS share the same biosynthetic pathway, we hypothesized that heparin could be produced in CHO cells by metabolic engineering. Based on the expression of endogenous enzymes in the HS / heparin pathways of CHO-S cells, human N-deacetylase/N-sulfotransferase (NDST2) and mouse heparan sulfate 3-O-sulfotransferase 1 (Hs3st1) genes were transfected sequentially into CHO host cells growing in suspension culture. Transfectants were screened using quantitative RT-PCR and Western blotting. Out of 120 clones expressing NDST2 and Hs3st1, 2 clones, Dual-3 and Dual-29, were selected for further analysis. An antithrombin III (ATIII) binding assay using flow cytometry, designed to recognize a key sugar structure characteristic of heparin, indicated that Hs3st1 transfection was capable of increasing ATIII binding. An anti-factor Xa assay, which affords a measure of anticoagulant activity, showed a significant increase in activity in the dual-expressing cell lines. Disaccharide analysis of the engineered HS showed a substantial increase in N-sulfo groups, but did not show a pattern consistent with pharmacological heparin, suggesting that further balancing the expression of transgenes with the expression levels of endogenous enzymes involved in HS / heparin biosynthesis might be necessary. PMID:22326251

Methylation of L1Hs promoters is lower on the inactive X, has a tendency of being higher on autosomes in smaller genomes and shows inter-individual variability at some loci.

PubMed

Singer, Heike; Walier, Maja; Nüsgen, Nicole; Meesters, Christian; Schreiner, Felix; Woelfle, Joachim; Fimmers, Rolf; Wienker, Thomas; Kalscheuer, Vera M; Becker, Tim; Schwaab, Rainer; Oldenburg, Johannes; El-Maarri, Osman

2012-01-01

LINE-1 repeats account for ~17% of the human genome. Little is known about their individual methylation patterns, because their repetitive, almost identical sequences make them difficult to be individually targeted. Here, we used bisulfite conversion to study methylation at individual LINE-1 repeats. The loci studied included 39 X-linked loci and 5 autosomal loci. On the X chromosome in women, we found statistically significant less methylation at almost all L1Hs compared with men. Methylation at L1P and L1M did not correlate with the inactivation status of the host DNA, while the majority of L1Hs that were possible to be studied lie in inactivated regions. To investigate whether the male-female differences at L1Hs on the X are linked to the inactivation process itself rather than to a mere influence of gender, we analyzed six of the L1Hs loci on the X chromosome in Turners and Klinefelters which have female and male phenotype, respectively, but with reversed number of X chromosomes. We could confirm that all samples with two X chromosomes are hypomethylated at the L1Hs loci. Therefore, the inactive X is hypomethylated at L1Hs; the latter could play an exclusive role in the X chromosome inactivation process. At autosomal L1Hs, methylation levels showed a correlation tendency between methylation level and genome size, with higher methylation observed at most loci in individuals with one X chromosome and the lowest in XXY individuals. In summary, loci-specific LINE-1 methylation levels show considerable plasticity and depend on genomic position and constitution.

Methylation of L1Hs promoters is lower on the inactive X, has a tendency of being higher on autosomes in smaller genomes and shows inter-individual variability at some loci

PubMed Central

Singer, Heike; Walier, Maja; Nüsgen, Nicole; Meesters, Christian; Schreiner, Felix; Woelfle, Joachim; Fimmers, Rolf; Wienker, Thomas; Kalscheuer, Vera M.; Becker, Tim; Schwaab, Rainer; Oldenburg, Johannes; El-Maarri, Osman

2012-01-01

LINE-1 repeats account for ∼17% of the human genome. Little is known about their individual methylation patterns, because their repetitive, almost identical sequences make them difficult to be individually targeted. Here, we used bisulfite conversion to study methylation at individual LINE-1 repeats. The loci studied included 39 X-linked loci and 5 autosomal loci. On the X chromosome in women, we found statistically significant less methylation at almost all L1Hs compared with men. Methylation at L1P and L1M did not correlate with the inactivation status of the host DNA, while the majority of L1Hs that were possible to be studied lie in inactivated regions. To investigate whether the male–female differences at L1Hs on the X are linked to the inactivation process itself rather than to a mere influence of gender, we analyzed six of the L1Hs loci on the X chromosome in Turners and Klinefelters which have female and male phenotype, respectively, but with reversed number of X chromosomes. We could confirm that all samples with two X chromosomes are hypomethylated at the L1Hs loci. Therefore, the inactive X is hypomethylated at L1Hs; the latter could play an exclusive role in the X chromosome inactivation process. At autosomal L1Hs, methylation levels showed a correlation tendency between methylation level and genome size, with higher methylation observed at most loci in individuals with one X chromosome and the lowest in XXY individuals. In summary, loci-specific LINE-1 methylation levels show considerable plasticity and depend on genomic position and constitution. PMID:21972244

Impact of intratumoural heterogeneity on the assessment of Ki67 expression in breast cancer.

PubMed

Aleskandarany, M A; Green, A R; Ashankyty, I; Elmouna, A; Diez-Rodriguez, M; Nolan, C C; Ellis, I O; Rakha, E A

2016-07-01

In breast cancer (BC), the prognostic value of Ki67 expression is well-documented. Intratumoural heterogeneity (ITH) of Ki67 expression is amongst the several technical issues behind the lag of its inclusion into BC prognostic work-up. The immunohistochemical (IHC) expression of anti-Ki67 antibody (MIB1 clone) was assessed in four full-face (FF) sections from different primary tumour blocks and their matched axillary nodal (LN) metastases in a series of 55 BC. Assessment was made using the highest expression hot spots (HS), lowest expression (LS), and overall/average expression scores (AS) in each section. Heterogeneity score (Hes), co-efficient of variation, and correlation co-efficient were used to assess the levels of Ki67 ITH. Ki67 HS, LS, and AS scores were highly variable within the same section and between different sections of the primary tumour, with maximal variation observed in the LS (P < 0.001). The least variability between the different slides was observed with HS scoring. Although the associations between Ki67 and clinicopathological and molecular variables were similar when using HS or AS, the best correlation between AS and HS was observed in tumours with high Ki67 expression only. Ki67 expression in LN deposits was less heterogeneous than in the primary tumours and was perfectly correlated with the HS Ki67 expression in the primary tumour sections (r = 0.98, P < 0.001). In conclusion, assessment of Ki67 expression using HS scoring method on a full-face BC tissue section can represent the primary tumour growth fraction that is likely to metastasise. The association between Ki67 expression pattern in the LN metastasis and the HS in the primary tumour may reflect the temporal heterogeneity through clonal expansion.

The human homolog of S. cerevisiae CDC27, CDC27 Hs, is encoded by a highly conserved intronless gene present in multiple copies in the human genome

DOE Office of Scientific and Technical Information (OSTI.GOV)

Devor, E.J.; Dill-Devor, R.M.

1994-09-01

We have obtained a number of unique sequences via PCR amplification of human genomic DNA using degenerate primers under low stringency (42{degrees}C). One of these, an 853 bp product, has been identified as a partial genomic sequence of the human homolog of the S. cerevisiae CDC27 gene, CDC27Hs (GenBank No. U00001). This gene, reported by Turgendreich et al. is also designated EST00556 from Adams et al. We have undertaken a more detailed examination of our sequence, MCP34N, and have found that: 1. the genomic sequence is nearly identical to CDC27Hs over its entire 853 bp length; 2. an MCP34N-specific PCRmore » assay of several non-human primate species reveals amplification products in chimpanzee and gorilla genomes having greater than 90% sequence identity with CDC27Hs; and 3. an MCP34N-specific PCR assay of the BIOS hybrid cell line panel gives a discordancy pattern suggesting multiple loci. Based upon these data, we present the following initial characterization: 1. the complete MCP34N sequence identity with CDC27Hs indicates that the latter is encoded by an intronless gene; 2. CDC27Hs is highly conserved among higher primates; and 3. CDC27Hs is present in multiple copies in the human genome. These characteristics, taken together with those initially reported for CDC27Hs, suggest that this is an old gene that carries out an important but, as yet, unknown function in the human brain.« less

Metabolic engineering of Chinese hamster ovary cells: towards a bioengineered heparin.

PubMed

Baik, Jong Youn; Gasimli, Leyla; Yang, Bo; Datta, Payel; Zhang, Fuming; Glass, Charles A; Esko, Jeffrey D; Linhardt, Robert J; Sharfstein, Susan T

2012-03-01

Heparin is the most widely used pharmaceutical to control blood coagulation in modern medicine. A health crisis that took place in 2008 led to a demand for production of heparin from non-animal sources. Chinese hamster ovary (CHO) cells, commonly used mammalian host cells for production of foreign pharmaceutical proteins in the biopharmaceutical industry, are capable of producing heparan sulfate (HS), a related polysaccharide naturally. Since heparin and HS share the same biosynthetic pathway, we hypothesized that heparin could be produced in CHO cells by metabolic engineering. Based on the expression of endogenous enzymes in the HS/heparin pathways of CHO-S cells, human N-deacetylase/N-sulfotransferase (NDST2) and mouse heparan sulfate 3-O-sulfotransferase 1 (Hs3st1) genes were transfected sequentially into CHO host cells growing in suspension culture. Transfectants were screened using quantitative RT-PCR and Western blotting. Out of 120 clones expressing NDST2 and Hs3st1, 2 clones, Dual-3 and Dual-29, were selected for further analysis. An antithrombin III (ATIII) binding assay using flow cytometry, designed to recognize a key sugar structure characteristic of heparin, indicated that Hs3st1 transfection was capable of increasing ATIII binding. An anti-factor Xa assay, which affords a measure of anticoagulant activity, showed a significant increase in activity in the dual-expressing cell lines. Disaccharide analysis of the engineered HS showed a substantial increase in N-sulfo groups, but did not show a pattern consistent with pharmacological heparin, suggesting that further balancing the expression of transgenes with the expression levels of endogenous enzymes involved in HS/heparin biosynthesis might be necessary. Copyright © 2012 Elsevier Inc. All rights reserved.

Modifying mental health help-seeking stigma among undergraduates with untreated psychiatric disorders: A pilot randomized trial of a novel cognitive bias modification intervention.

PubMed

Stanley, Ian H; Hom, Melanie A; Joiner, Thomas E

2018-04-01

Help-seeking stigma is a potent barrier to the utilization of mental health services. This study aimed to determine if, compared to a psychoeducation condition, individuals randomized to a novel cognitive bias modification intervention for help-seeking stigma (CBM-HS) demonstrate greater reductions in help-seeking stigma, as well as increases in readiness to change and help-seeking behaviors. Participants included 32 undergraduates with a DSM-5 psychiatric disorder who denied past-year mental health treatment. Post-randomization, three intervention sessions were delivered in one-week intervals (45 min total). Participants were assessed at baseline, mid-intervention, one-week post-intervention, and two-month follow-up. RM-ANOVAs were utilized among the intent-to-treat sample. There were no significant differences across time points between the intervention groups for help-seeking stigma and readiness to change. At two-month follow-up, 25% of participants initiated mental health treatment (29.4% CBM-HS, 20.0% psychoeducation). Strikingly, across groups, there was a statistically significant reduction in help-seeking self-stigma (F[2.214,66.418] = 5.057, p = 0.007, η p 2  = 0.144) and perceived public stigma (F[3,90] = 6.614, p < 0.001, η p 2  = 0.181) from baseline to two-month follow-up, indicating large effects; 18.8% achieved clinically significant change, among whom two-thirds were in the CBM-HS condition. Two brief, scalable interventions appear to reduce help-seeking stigma among undergraduates with untreated psychiatric disorders. Studies are needed to evaluate these interventions against an inactive control. Copyright © 2018 Elsevier Ltd. All rights reserved.

Quantum renormalizations in anisotropic multisublattice magnets and the modification of magnetic susceptibility under irradiation

NASA Astrophysics Data System (ADS)

Val'kov, V. V.; Shustin, M. S.

2015-11-01

The dispersion equation of a strongly anisotropic one-dimensional magnet catena-[FeII(ClO4)2{FeIII(bpca)2}]ClO4 containing alternating high-spin (HS) ( S = 2) and low-spin (LS) ( S = 1/2) iron ions is obtained by the diagram technique for Hubbard operators. The analysis of this equation yields six branches in the excitation spectrum of this magnet. It is important that the crystal field for ions with spin S = 2 is described by the Hamiltonian of single-ion easy-plane anisotropy, whose orientation is changed by 90° when passing from one HS iron ion to another. The U( N) transformation technique in the atomic representation is applied to diagonalize a single-ion Hamiltonian with a large number of levels. It is shown that the modulation of the orientation of easy magnetization planes leads to a model of a ferrimagnet with easy-axis anisotropy and to the formation of energy spectrum with a large gap. For HS iron ions, a decrease in the mean value of the spin projection due to quantum fluctuations is calculated. The analysis of the specific features of the spectrum of elementary excitations allows one to establish a correspondence to a generalized Ising model for which the magnetic susceptibility is calculated in a wide range of temperatures by the transfer-matrix method. The introduction of a statistical ensemble that takes into account the presence of chains of different lengths and the presence of iron ions with different spins allows one to describe the experimentally observed modification of the magnetic susceptibility of the magnet under optical irradiation.

Inhibition of Human Metapneumovirus Binding to Heparan Sulfate Blocks Infection in Human Lung Cells and Airway Tissues

PubMed Central

Klimyte, Edita M.; Smith, Stacy E.; Oreste, Pasqua; Lembo, David

2016-01-01

ABSTRACT Human metapneumovirus (HMPV), a recently discovered paramyxovirus, infects nearly 100% of the world population and causes severe respiratory disease in infants, the elderly, and immunocompromised patients. We previously showed that HMPV binds heparan sulfate proteoglycans (HSPGs) and that HMPV binding requires only the viral fusion (F) protein. To characterize the features of this interaction critical for HMPV binding and the role of this interaction in infection in relevant models, we utilized sulfated polysaccharides, heparan sulfate mimetics, and occluding compounds. Iota-carrageenan demonstrated potent anti-HMPV activity by inhibiting binding to lung cells mediated by the F protein. Furthermore, analysis of a minilibrary of variably sulfated derivatives of Escherichia coli K5 polysaccharide mimicking the HS structure revealed that the highly O-sulfated K5 polysaccharides inhibited HMPV infection, identifying a potential feature of HS critical for HMPV binding. The peptide dendrimer SB105-A10, which binds HS, reduced binding and infection in an F-dependent manner, suggesting that occlusion of HS at the target cell surface is sufficient to prevent infection. HMPV infection was also inhibited by these compounds during apical infection of polarized airway tissues, suggesting that these interactions take place during HMPV infection in a physiologically relevant model. These results reveal key features of the interaction between HMPV and HS, supporting the hypothesis that apical HS in the airway serves as a binding factor during infection, and HS modulating compounds may serve as a platform for potential antiviral development. IMPORTANCE Human metapneumovirus (HMPV) is a paramyxovirus that causes respiratory disease worldwide. It has been previously shown that HMPV requires binding to heparan sulfate on the surfaces of target cells for attachment and infection. In this study, we characterize the key features of this binding interaction using heparan sulfate mimetics, identify an important sulfate modification, and demonstrate that these interactions occur at the apical surface of polarized airway tissues. These findings provide insights into the initial binding step of HMPV infection that has potential for antiviral development. PMID:27489270

Characterization and possible function of glyceraldehyde-3-phosphate dehydrogenase-spermatogenic protein GAPDHS in mammalian sperm.

PubMed

Margaryan, Hasmik; Dorosh, Andriy; Capkova, Jana; Manaskova-Postlerova, Pavla; Philimonenko, Anatoly; Hozak, Pavel; Peknicova, Jana

2015-03-08

Sperm proteins are important for the sperm cell function in fertilization. Some of them are involved in the binding of sperm to the egg. We characterized the acrosomal sperm protein detected by a monoclonal antibody (MoAb) (Hs-8) that was prepared in our laboratory by immunization of BALB/c mice with human ejaculated sperms and we tested the possible role of this protein in the binding assay. Indirect immunofluorescence and immunogold labelling, gel electrophoresis, Western blotting and protein sequencing were used for Hs-8 antigen characterization. Functional analysis of GAPDHS from the sperm acrosome was performed in the boar model using sperm/zona pellucida binding assay. Monoclonal antibody Hs-8 is an anti-human sperm antibody that cross-reacts with the Hs-8-related protein in spermatozoa of other mammalian species (boar, mouse). In the immunofluorescence test, Hs-8 antibody recognized the protein localized in the acrosomal part of the sperm head and in the principal piece of the sperm flagellum. In immunoblotting test, MoAb Hs-8 labelled a protein of 45 kDa in the extract of human sperm. Sequence analysis identified protein Hs-8 as GAPDHS (glyceraldehyde 3-phosphate dehydrohenase-spermatogenic). For this reason, commercial mouse anti-GAPDHS MoAb was applied in control tests. Both antibodies showed similar staining patterns in immunofluorescence tests, in electron microscopy and in immunoblot analysis. Moreover, both Hs-8 and anti-GAPDHS antibodies blocked sperm/zona pellucida binding. GAPDHS is a sperm-specific glycolytic enzyme involved in energy production during spermatogenesis and sperm motility; its role in the sperm head is unknown. In this study, we identified the antigen with Hs8 antibody and confirmed its localization in the apical part of the sperm head in addition to the principal piece of the flagellum. In an indirect binding assay, we confirmed the potential role of GAPDHS as a binding protein that is involved in the secondary sperm/oocyte binding.

Roles of Heparan Sulfate Sulfation in Dentinogenesis*

PubMed Central

Hayano, Satoru; Kurosaka, Hiroshi; Yanagita, Takeshi; Kalus, Ina; Milz, Fabian; Ishihara, Yoshihito; Islam, Md. Nurul; Kawanabe, Noriaki; Saito, Masahiro; Kamioka, Hiroshi; Adachi, Taiji; Dierks, Thomas; Yamashiro, Takashi

2012-01-01

Cell surface heparan sulfate (HS) is an essential regulator of cell signaling and development. HS traps signaling molecules, like Wnt in the glycosaminoglycan side chains of HS proteoglycans (HSPGs), and regulates their functions. Endosulfatases Sulf1 and Sulf2 are secreted at the cell surface to selectively remove 6-O-sulfate groups from HSPGs, thereby modifying the affinity of cell surface HSPGs for its ligands. This study provides molecular evidence for the functional roles of HSPG sulfation and desulfation in dentinogenesis. We show that odontogenic cells are highly sulfated on the cell surface and become desulfated during their differentiation to odontoblasts, which produce tooth dentin. Sulf1/Sulf2 double null mutant mice exhibit a thin dentin matrix and short roots combined with reduced expression of dentin sialophosphoprotein (Dspp) mRNA, encoding a dentin-specific extracellular matrix precursor protein, whereas single Sulf mutants do not show such defective phenotypes. In odontoblast cell lines, Dspp mRNA expression is potentiated by the activation of the Wnt canonical signaling pathway. In addition, pharmacological interference with HS sulfation promotes Dspp mRNA expression through activation of Wnt signaling. On the contrary, the silencing of Sulf suppresses the Wnt signaling pathway and subsequently Dspp mRNA expression. We also show that Wnt10a protein binds to cell surface HSPGs in odontoblasts, and interference with HS sulfation decreases the binding affinity of Wnt10a for HSPGs, which facilitates the binding of Wnt10a to its receptor and potentiates the Wnt signaling pathway, thereby up-regulating Dspp mRNA expression. These results demonstrate that Sulf-mediated desulfation of cellular HSPGs is an important modification that is critical for the activation of the Wnt signaling in odontoblasts and for production of the dentin matrix. PMID:22351753

Proteomic Identification of Heat Shock-Induced Danger Signals in a Melanoma Cell Lysate Used in Dendritic Cell-Based Cancer Immunotherapy.

PubMed

González, Fermín E; Chernobrovkin, Alexey; Pereda, Cristián; García-Salum, Tamara; Tittarelli, Andrés; López, Mercedes N; Salazar-Onfray, Flavio; Zubarev, Roman A

2018-01-01

Autologous dendritic cells (DCs) loaded with cancer cell-derived lysates have become a promising tool in cancer immunotherapy. During the last decade, we demonstrated that vaccination of advanced melanoma patients with autologous tumor antigen presenting cells (TAPCells) loaded with an allogeneic heat shock- (HS-) conditioned melanoma cell-derived lysate (called TRIMEL) is able to induce an antitumor immune response associated with a prolonged patient survival. TRIMEL provides not only a broad spectrum of potential melanoma-associated antigens but also danger signals that are crucial in the induction of a committed mature DC phenotype. However, potential changes induced by heat conditioning on the proteome of TRIMEL are still unknown. The identification of newly or differentially expressed proteins under defined stress conditions is relevant for understanding the lysate immunogenicity. Here, we characterized the proteomic profile of TRIMEL in response to HS treatment. A quantitative label-free proteome analysis of over 2800 proteins was performed, with 91 proteins that were found to be regulated by HS treatment: 18 proteins were overexpressed and 73 underexpressed. Additionally, 32 proteins were only identified in the HS-treated TRIMEL and 26 in non HS-conditioned samples. One protein from the overexpressed group and two proteins from the HS-exclusive group were previously described as potential damage-associated molecular patterns (DAMPs). Some of the HS-induced proteins, such as haptoglobin, could be also considered as DAMPs and candidates for further immunological analysis in the establishment of new putative danger signals with immunostimulatory functions.

Proteomic Identification of Heat Shock-Induced Danger Signals in a Melanoma Cell Lysate Used in Dendritic Cell-Based Cancer Immunotherapy

PubMed Central

Chernobrovkin, Alexey; Pereda, Cristián; García-Salum, Tamara; Tittarelli, Andrés; López, Mercedes N.; Salazar-Onfray, Flavio

2018-01-01

Autologous dendritic cells (DCs) loaded with cancer cell-derived lysates have become a promising tool in cancer immunotherapy. During the last decade, we demonstrated that vaccination of advanced melanoma patients with autologous tumor antigen presenting cells (TAPCells) loaded with an allogeneic heat shock- (HS-) conditioned melanoma cell-derived lysate (called TRIMEL) is able to induce an antitumor immune response associated with a prolonged patient survival. TRIMEL provides not only a broad spectrum of potential melanoma-associated antigens but also danger signals that are crucial in the induction of a committed mature DC phenotype. However, potential changes induced by heat conditioning on the proteome of TRIMEL are still unknown. The identification of newly or differentially expressed proteins under defined stress conditions is relevant for understanding the lysate immunogenicity. Here, we characterized the proteomic profile of TRIMEL in response to HS treatment. A quantitative label-free proteome analysis of over 2800 proteins was performed, with 91 proteins that were found to be regulated by HS treatment: 18 proteins were overexpressed and 73 underexpressed. Additionally, 32 proteins were only identified in the HS-treated TRIMEL and 26 in non HS-conditioned samples. One protein from the overexpressed group and two proteins from the HS-exclusive group were previously described as potential damage-associated molecular patterns (DAMPs). Some of the HS-induced proteins, such as haptoglobin, could be also considered as DAMPs and candidates for further immunological analysis in the establishment of new putative danger signals with immunostimulatory functions. PMID:29744371

Resveratrol analog, HS-1793 enhance anti-tumor immunity by reducing the CD4+CD25+ regulatory T cells in FM3A tumor bearing mice.

PubMed

Jeong, Min Ho; Yang, Kwang Mo; Choi, Yoo Jin; Kim, Sung Dae; Yoo, Young Hyun; Seo, Su Yeong; Lee, Sang Hwa; Ryu, Seong Ryul; Lee, Chang Min; Suh, Hong suk; Jo, Wol Soon

2012-11-01

Natural agents with the immunomodulating property have been gaining traction to be employed in the complementary therapy of cancer because the ineffectiveness of numerous therapeutic strategies may be related in part to the tumor-induced immunosuppressive phenotypes, especially regulatory T (Treg) cells found in the tumor microenvironment. The present study was undertaken to examine whether HS-1793, synthetic resvertrol analog free from the restriction of metabolic instability and high dose requirement of resveratrol, induces an in vivo anti-tumor effect in FM3A tumor bearing mice through the suppression of Treg cells, which contribute to an increase in tumor specific cytotoxic T cell responses. Intraperitoneal injections of HS-1793 showed not only therapeutic benefits on established tumors, but also preventive anti-tumor effects. Treg cells (CD4+CD25+Foxp3+ cells) were significantly reduced in the total splenocytes as well as tumor tissues from HS-1793-administered mice, and the production of TGF-β inducing Treg showed a similar pattern. On the contrary, the administration of HS-1793 increased IFN-γ-expressing CD8+ T cells, upregulated IFN-γ production, and enhanced the cytotoxicity of splenocytes against FM3A tumor cells both in therapeutic and preventive experimental animals. These results demonstrated the suppressive role of HS-1793 on the function of Treg cells contributing to tumor specific cytotoxic T lymphocyte responses in tumor-bearing mice, which explained the underlying mechanism of the anti-tumor immunity of HS-1793. Copyright © 2012 Elsevier B.V. All rights reserved.

Heparan sulfate proteoglycans undergo differential expression alterations in right sided colorectal cancer, depending on their metastatic character.

PubMed

Fernández-Vega, Iván; García-Suárez, Olivia; García, Beatriz; Crespo, Ainara; Astudillo, Aurora; Quirós, Luis M

2015-10-20

Heparan sulfate proteoglycans (HSPGs) are complex molecules involved in the growth, invasion and metastatic properties of cancerous cells. This study analyses the alterations in the expression patterns of these molecules in right sided colorectal cancer (CRC), both metastatic and non-metastatic. Twenty right sided CRCs were studied. A transcriptomic approach was used, employing qPCR to analyze both the expression of the enzymes involved in heparan sulfate (HS) chains biosynthesis, as well as the proteoglycan core proteins. Since some of these proteoglycans can also carry chondroitin sulfate (CS) chains, we include the study of the genes involved in the biosynthesis of these glycosaminoglycans. Immunohistochemical techniques were also used to analyze tissue expression of particular genes showing significant expression differences, of potential interest. Changes in proteoglycan core proteins differ depending on their location; those located intracellularly or in the extracellular matrix show very similar alteration patterns, while those located on the cell surface vary greatly depending on the nature of the tumor: glypicans 1, 3, 6 and betaglycan are affected in the non-metastatic tumors, whereas in the metastatic, only glypican-1 and syndecan-1 are modified, the latter showing opposing alterations in levels of RNA and of protein, suggesting post-transcriptional regulation in these tumors. Furthermore, in non-metastatic tumors, polymerization of glycosaminoglycan chains is modified, particularly affecting the synthesis of the tetrasaccharide linker and the initiation and elongation of CS chains, HS chains being less affected. Regarding the enzymes responsible for the modificaton of the HS chains, alterations were only found in non-metastatic tumors, affecting N-sulfation and the isoforms HS6ST1, HS3ST3B and HS3ST5. In contrast, synthesis of the CS chains suggests changes in epimerization and sulfation of the C4 and C2 in both types of tumor. Right sided CRCs show alterations in the expression of HSPGs, including the expression of the cell surface core proteins, many glycosiltransferases and some enzymes that modify the HS chains depending on the metastatic nature of the tumor, resulting more affected in non-metastatic ones. However, matrix proteoglycans and enzymes involved in CS fine structure synthesis are extensively modified independetly of the presence of lymph node metastasis.

Human serum and platelet lysate are appropriate xeno-free alternatives for clinical-grade production of human MuStem cell batches.

PubMed

Saury, Charlotte; Lardenois, Aurélie; Schleder, Cindy; Leroux, Isabelle; Lieubeau, Blandine; David, Laurent; Charrier, Marine; Guével, Laëtitia; Viau, Sabrina; Delorme, Bruno; Rouger, Karl

2018-05-02

Canine MuStem cells have demonstrated regenerative efficacy in a dog model of muscular dystrophy, and the recent characterization of human counterparts (hMuStem) has highlighted the therapeutic potential of this muscle-derived stem cell population. To date, these cells have only been generated in research-grade conditions. However, evaluation of the clinical efficacy of any such therapy will require the production of hMuStem cells in compliance with good manufacturing practices (GMPs). Because the current use of fetal bovine serum (FBS) to isolate and expand hMuStem cells raises several ethical, safety, and supply concerns, we assessed the use of two alternative xeno-free blood derivatives: human serum (HS) and a human platelet lysate (hPL). hMuStem cells were isolated and expanded in vitro in either HS-supplemented or hPL-supplemented media and the proliferation rate, clonogenicity, myogenic commitment potential, and oligopotency compared with that observed in FBS-supplemented medium. Flow cytometry and high-throughput 3'-digital gene expression RNA sequencing were used to characterize the phenotype and global gene expression pattern of hMuStem cells cultured with HS or hPL. HS-supplemented and hPL-supplemented media both supported the isolation and long-term proliferation of hMuStem cells. Compared with FBS-based medium, both supplements enhanced clonogenicity and allowed for a reduction in growth factor supplementation. Neither supplement altered the cell lineage pattern of hMuStem cells. In vitro differentiation assays revealed a decrease in myogenic commitment and in the fusion ability of hMuStem cells when cultured with hPL. In return, this reduction of myogenic potential in hPL-supplemented cultures was rapidly reversed by substitution of hPL with HS or fibrinogen-depleted hPL. Moreover, culture of hMuStem cells in hPL hydrogel and fibrinogen-depleted hPL demonstrated that myogenic differentiation potential is maintained in heparin-free hPL derivatives. Our findings indicate that HS and hPL are efficient and viable alternatives to FBS for the preparation of hMuStem cell batches in compliance with GMPs.

Crystallization and preliminary crystallographic analysis of human Atg4B–LC3 complex

DOE Office of Scientific and Technical Information (OSTI.GOV)

Satoo, Kenji; Suzuki, Nobuo N.; Fujioka, Yuko

2007-02-01

Human Atg4B and LC3 were expressed, purified and crystallized as a complex. Diffraction data were collected to a resolution of 1.9 Å. The reversible modification of Atg8 with phosphatidylethanolamine (PE) is crucial for autophagy, the bulk degradation process of cytoplasmic components by the vacuolar/lysosomal system. Atg4 is a cysteine protease that is responsible for the processing and deconjugation of Atg8. Human Atg4B (HsAtg4B; a mammalian orthologue of yeast Atg4) and LC3 (a mammalian orthologue of yeast Atg8) were expressed and purified and two complexes, one consisting of HsAtg4B(1–354) and LC3(1–120) (complex I; the product complex) and the other consisting ofmore » HsAtg4B(1–354) and LC3(1–124) (complex II; the substrate complex), were crystallized using polyethylene glycol 3350 as a precipitant. In both complexes His280 of HsAtg4B was mutated to alanine. The crystals belong to the same space group P2{sub 1}2{sub 1}2{sub 1}, with unit-cell parameters a = 47.5, b = 91.8, c = 102.6 Å for complex I and a = 46.9, b = 90.9, c = 102.5 Å for complex II. Diffraction data were collected to a resolution of 1.9 Å from both crystals.« less

The progress of inflammation and oxidative stress in patients with chronic kidney disease.

PubMed

Xu, Gaosi; Luo, Kaiping; Liu, Huixin; Huang, Tianlun; Fang, Xiangdong; Tu, Weiping

2015-02-01

The variations and their correlation of inflammation and oxidative stress in chronic kidney disease (CKD) have not been thoroughly understood. Biomarkers of inflammation and oxidative stress were measured in a cohort of 176 patients with CKD ranging from stage 1 to 5 and 67 healthy controls. Correlation analysis in levels between inflammation and oxidative stress was also performed with estimated glomerular filtration rate (eGFR) using the Modification of Diet in Renal Disease (MDRD) formula. Concentrations of serum creatinine (Scr), hs-CRP (hypersensitive C reactive protein) and MDA (malondialdehyde) of these participants were measured again after 12 month follow-up. In the present study, with the development of CKD, serum levels of hs-CRP, interleukin-6 (IL-6) and MDA were significantly increased, and the serum levels of SOD (superoxide dismutase) and GSH-PX (glutathione peroxidase) were significantly decreased in these participants. eGFR was inversely associated with MDA and positively with SOD and GSH-PX when adjusting for age and hypertension therapy. IL-6 and hs-CRP were positively correlated with MDA, and negatively associated with SOD and GSH-PX. Notably, after 12-month follow-up, the increase in Scr was positively associated with the increase in hs-CRP (p < 0.01) and MDA (p < 0.05), respectively. Inflammation and oxidative stress interacted with each other and played pivotal roles in the development of CKD. Variation in eGFR was parallel with the changes of oxidative stress and inflammation when CKD developing.

Exploring the Dynamics of Dyadic Interactions via Hierarchical Segmentation

ERIC Educational Resources Information Center

Hsieh, Fushing; Ferrer, Emilio; Chen, Shu-Chun; Chow, Sy-Miin

2010-01-01

In this article we present an exploratory tool for extracting systematic patterns from multivariate data. The technique, hierarchical segmentation (HS), can be used to group multivariate time series into segments with similar discrete-state recurrence patterns and it is not restricted by the stationarity assumption. We use a simulation study to…

Heparan sulfate C5-epimerase is essential for heparin biosynthesis in mast cells.

PubMed

Feyerabend, Thorsten B; Li, Jin-Ping; Lindahl, Ulf; Rodewald, Hans-Reimer

2006-04-01

Biosynthesis of heparin, a mast cell-derived glycosaminoglycan with widespread importance in medicine, has not been fully elucidated. In biosynthesis of heparan sulfate (HS), a structurally related polysaccharide, HS glucuronyl C5-epimerase (Hsepi) converts D-glucuronic acid (GlcA) to L-iduronic acid (IdoA) residues. We have generated Hsepi-null mouse mutant mast cells, and we show that the same enzyme catalyzes the generation of IdoA in heparin and that 'heparin' lacking IdoA shows a distorted O-sulfation pattern.

Development of a Direct Headspace Collection Method from Arabidopsis Seedlings Using HS-SPME-GC-TOF-MS Analysis

PubMed Central

Kusano, Miyako; Iizuka, Yumiko; Kobayashi, Makoto; Fukushima, Atsushi; Saito, Kazuki

2013-01-01

Plants produce various volatile organic compounds (VOCs), which are thought to be a crucial factor in their interactions with harmful insects, plants and animals. Composition of VOCs may differ when plants are grown under different nutrient conditions, i.e., macronutrient-deficient conditions. However, in plants, relationships between macronutrient assimilation and VOC composition remain unclear. In order to identify the kinds of VOCs that can be emitted when plants are grown under various environmental conditions, we established a conventional method for VOC profiling in Arabidopsis thaliana (Arabidopsis) involving headspace-solid-phase microextraction-gas chromatography-time-of-flight-mass spectrometry (HS-SPME-GC-TOF-MS). We grew Arabidopsis seedlings in an HS vial to directly perform HS analysis. To maximize the analytical performance of VOCs, we optimized the extraction method and the analytical conditions of HP-SPME-GC-TOF-MS. Using the optimized method, we conducted VOC profiling of Arabidopsis seedlings, which were grown under two different nutrition conditions, nutrition-rich and nutrition-deficient conditions. The VOC profiles clearly showed a distinct pattern with respect to each condition. This study suggests that HS-SPME-GC-TOF-MS analysis has immense potential to detect changes in the levels of VOCs in not only Arabidopsis, but other plants grown under various environmental conditions. PMID:24957989

Dynamics and sources of reduced sulfur, humic substances and dissolved organic carbon in a temperate river system affected by agricultural practices.

PubMed

Marie, Lauriane; Pernet-Coudrier, Benoît; Waeles, Matthieu; Gabon, Marine; Riso, Ricardo

2015-12-15

Although reduced organic sulfur substances (RSS) as well as humic substances (HS) are widely suspected to play a role in, for example, metal speciation or used as a model of dissolved organic carbon (DOC) in laboratory studies, reports of their quantification in natural waters are scarce. We have examined the dynamics and sources of reduced sulfur, HS and DOC over an annual cycle in a river system affected by agricultural practices. The new differential pulse cathodic stripping voltammetry was successfully applied to measure glutathione-like compounds (GSHs), thioacetamide-like compounds (TAs) and the liquid chromatography coupled to organic detector to analyze HS and DOC at high frequency in the Penzé River (NW France). The streamflow-concentration patterns, principal components analysis and flux analysis allowed discrimination of the source of each organic compound type. Surprisingly, the two RSS and HS detected in all samples, displayed different behavior. As previously shown, manuring practice is the main source of DOC and HS in this watershed where agricultural activity is predominant. The HS were then transferred to the river systems via runoff, particularly during the spring and autumn floods, which are responsible of >60% of the annual flux. TAs had a clear groundwater source and may be formed underground, whereas GSHs displayed two sources: one aquagenic in spring and summer probably linked to the primary productivity and a second, which may be related to bacterial degradation. High sampling frequency allowed a more accurate assessment of the flux values which were 280 tC y(-1) for DOC representing 20 kg C ha(-1) y(-1). HS, TAs and GSHs fluxes represented 60, 13, and 4% of the total annual DOC export, respectively. Copyright © 2015 Elsevier B.V. All rights reserved.

Characterization of CaHsp70-1, a Pepper Heat-Shock Protein Gene in Response to Heat Stress and Some Regulation Exogenous Substances in Capsicum annuum L.

PubMed Central

Guo, Meng; Zhai, Yu-Fei; Lu, Jin-Ping; Chai, Lin; Chai, Wei-Guo; Gong, Zhen-Hui; Lu, Ming-Hui

2014-01-01

Pepper (Capsicum annuum L.) is sensitive to heat stress (HS). Heat shock proteins 70 (Hsp70s) play a crucial role in protecting plant cells against HS and control varies characters in different plants. However, CaHsp70-1 gene was not well characterized in pepper. In this study, CaHsp70-1 was cloned from the pepper thermotolerant line R9, which encoded a protein of 652 amino acids, with a molecular weight of 71.54 kDa and an isoelectric point of 5.20. CaHsp70-1 belongs to the cytosolic Hsp70 subgroup, and best matched with tomato SlHsp70. CaHsp70-1 was highly induced in root, stem, leaf and flower in R9 with HS treatment (40 °C for 2 h). In both thermosensitive line B6 and thermotolerant line R9, CaHsp70-1 significantly increased after 0.5 h of HS (40 °C), and maintained in a higher level after 4 h HS. The expression of CaHsp70-1 induced by CaCl2, H2O2 and putrescine (Put) under HS were difference between B6 and R9 lines. The different expression patterns may be related to the differences in promoters of CaHsp70-1 from the two lines. These results suggest that CaHsp70-1 as a member of cytosolic Hsp70 subgroup, may be involved in HS defense response via a signal transduction pathway contained Ca2+, H2O2 and Put. PMID:25356507

Hydrogen sulfide triggers late-phase preconditioning in postischemic small intestine by an NO- and p38 MAPK-dependent mechanism

PubMed Central

Yusof, Mozow; Kamada, Kazuhiro; Kalogeris, Theodore; Gaskin, F. Spencer; Korthuis, Ronald J.

2009-01-01

Hydrogen sulfide (H2S) is one of three endogenous gases, along with carbon monoxide (CO) and nitric oxide (NO), that exert a variety of important vascular actions in vivo. Although it has been demonstrated that CO or NO can trigger the development of a preconditioned phenotype in postischemic tissues, it is unclear whether H2S may also induce protection in organs subsequently exposed to ischemia-reperfusion (I/R). In light of these observations, we postulated that preconditioning with the exogenous H2S donor sodium hydrosulfide (NaHS-PC) would inhibit leukocyte rolling (LR) and adhesion (LA) induced by I/R. We used intravital microscopic techniques to demonstrate that NaHS-PC 24 h, but not 1 h, before I/R causes postcapillary venules to shift to an anti-inflammatory phenotype in wild-type (WT) mice such that these vessels fail to support LR and LA during reperfusion. The protective effect of NaHS-PC on LR was largely abolished by coincident pharmacological inhibition of NO synthase (NOS) in WT animals and was absent in endothelial NOS-deficient (eNOS−/−) mice. A similar pattern of response was noted in WT mice treated concomitantly with NaHS plus p38 mitogen-activated protein kinase (MAPK) inhibitors (SB 203580 or SK-86002). Whereas the reduction in LA induced by antecedent NaHS was attenuated by pharmacological inhibition of NOS or p38 MAPK in WT mice, the antiadhesive effect of NaHS was still evident in eNOS−/− mice. Thus NaHS-PC prevents LR and LA by triggering the activation of an eNOS- and p38 MAPK-dependent mechanism. However, the role of eNOS in the antiadhesive effect of NaHS-PC was less prominent than its effect to reduce LR. PMID:19168723

A four-disulphide-bridged toxin, with high affinity towards voltage-gated K+ channels, isolated from Heterometrus spinnifer (Scorpionidae) venom.

PubMed

Lebrun, B; Romi-Lebrun, R; Martin-Eauclaire, M F; Yasuda, A; Ishiguro, M; Oyama, Y; Pongs, O; Nakajima, T

1997-11-15

A new toxin, named HsTX1, has been identified in the venom of Heterometrus spinnifer (Scorpionidae), on the basis of its ability to block the rat Kv1.3 channels expressed in Xenopus oocytes. HsTX1 has been purified and characterized as a 34-residue peptide reticulated by four disulphide bridges. HsTX1 shares 53% and 59% sequence identity with Pandinus imperator toxin1 (Pi1) and maurotoxin, two recently isolated four-disulphide-bridged toxins, whereas it is only 32-47% identical with the other scorpion K+ channel toxins, reticulated by three disulphide bridges. The amidated and carboxylated forms of HsTX1 were synthesized chemically, and identity between the natural and the synthetic amidated peptides was proved by mass spectrometry, co-elution on C18 HPLC and blocking activity on the rat Kv1.3 channels. The disulphide bridge pattern was studied by (1) limited reduction-alkylation at acidic pH and (2) enzymic cleavage on an immobilized trypsin cartridge, both followed by mass and sequence analyses. Three of the disulphide bonds are connected as in the three-disulphide-bridged scorpion toxins, and the two extra half-cystine residues of HsTX1 are cross-linked, as in Pi1. These results, together with those of CD analysis, suggest that HsTX1 probably adopts the same general folding as all scorpion K+ channel toxins. HsTX1 is a potent inhibitor of the rat Kv1.3 channels (IC50 approx. 12 pM). HsTX1 does not compete with 125I-apamin for binding to its receptor site on rat brain synaptosomal membranes, but competes efficiently with 125I-kaliotoxin for binding to the voltage-gated K+ channels on the same preparation (IC50 approx. 1 pM).

New clinicopathological associations and histoprognostic markers in ILAE types of hippocampal sclerosis.

PubMed

Calderon-Garcidueñas, Ana Laura; Mathon, Bertrand; Lévy, Pierre; Bertrand, Anne; Mokhtari, Karima; Samson, Véronique; Thuriès, Valérie; Lambrecq, Virginie; Nguyen, Vi-Huong Michel; Dupont, Sophie; Adam, Claude; Baulac, Michel; Clémenceau, Stéphane; Duyckaerts, Charles; Navarro, Vincent; Bielle, Franck

2018-02-24

Mesial temporal lobe epilepsy with hippocampal sclerosis (MTLE-HS) is a heterogeneous syndrome. Surgery results in seizure freedom for most pharmacoresistant patients, but the epileptic and cognitive prognosis remains variable. The 2013 International League Against Epilepsy (ILAE) histopathological classification of hippocampal sclerosis (HS) has fostered research to understand MTLE-HS heterogeneity. We investigated the associations between histopathological features (ILAE types, hypertrophic CA4 neurons, granule cell layer alterations, CD34 immunopositive cells) and clinical features (presurgical history, postsurgical outcome) in a monocentric series of 247 MTLE-HS patients treated by surgery. NeuN, GFAP and CD34 immunostainings and a double independent pathological examination were performed. 186 samples were type 1, 47 type 2, 7 type 3 and 7 samples were gliosis only but no neuronal loss (noHS). In the type 1, hypertrophic CA4 neurons were associated with a worse postsurgical outcome and granule cell layer duplication was associated with generalized seizures and episodes of status epilepticus. In the type 2, granule cell layer duplication was associated with generalized seizures. CD34+ stellate cells were more frequent in the type 2, type 3 and in noHS. These cells had a Nestin and SOX2 positive, immature neural immunophenotype. Patients with nodules of CD34+ cells had more frequent dysmnesic auras. CD34+ stellate cells in scarce pattern were associated with higher ratio of normal MRI and of stereo-electroencephalographic studies. CD34+ cells were associated with a trend for a better postsurgical outcome. Among CD34+ cases, we proposed a new entity of BRAF V600E positive HS and we described three hippocampal multinodular and vacuolating neuronal tumors. To conclude, our data identified new clinicopathological associations with ILAE types. They showed the prognostic value of CA4 hypertrophic neurons. They highlighted CD34+ stellate cells and BRAF V600E as biomarkers to further decipher MTLE-HS heterogeneity. © 2018 International Society of Neuropathology.

Ultraviolet photography of the in vivo human cornea unmasks the Hudson-Stähli line and physiologic vortex patterns.

PubMed

Every, Sean G; Leader, John P; Molteno, Anthony C B; Bevin, Tui H; Sanderson, Gordon

2005-10-01

To perform ultraviolet (UV) macrophotography of the normal in vivo human cornea, establishing biometric data of the major component of UV absorption for comparison with the Hudson-Stähli (HS) line, the distribution of iron demonstrated by Perl stain, and cases of typical amiodarone keratopathy. Nonrandomized comparative case series of UV photographs of 76 normal corneas (group 1) and 16 corneas with typical amiodarone keratopathy (group 2). Image-analysis software was used to grade the major component of UV absorption for slope and the coordinates of its points of intersection with the vertical corneal meridian and inflection. In group 1 the major component had a mean slope of 5.8 degrees, sloping down from nasal to temporal cornea. The mean coordinates of points of intersection with the vertical corneal meridian and inflection were (0, 0.30) and (0.02, 0.31), respectively. No significant differences between groups 1 and 2 were found for slope (P = 0.155), intersection with the vertical corneal meridian (P = 0.517), and point of inflection (P = 0.344). The major component of UV absorption was consistent with published characteristics of the HS line, and coincidence of UV absorption and Perl-stained iron was demonstrated in one corneal button. A vortex pattern of UV absorption was observed in all corneas. UV photography demonstrates subclinical corneal iron, confirming its deposition in an integrated HS line/vortex pattern. Coincident iron and amiodarone deposition occurs in amiodarone keratopathy.

Dietary factors associated with subclinical inflammation among girls.

PubMed

Del Mar Bibiloni, M; Maffeis, C; Llompart, I; Pons, A; Tur, J A

2013-12-01

Dietary patterns and biomarkers of inflammation have been scarcely associated. The aim was to assess dietary factors associated with subclinical inflammation among girls. Fasting blood samples were collected from 12- to 17-year old girls (n=219) to measure adiponectin, leptin, tumor necrosis factor-alpha, plasminogen activator inhibitor 1 (PAI-1), interleukin-6 (IL-6) and high-sensitivity C-reactive protein (hs-CRP) levels. Body mass index (BMI) and waist-to-height ratio (WHtR), and food intake were also measured. Western (WDP) and Mediterranean (MDP) dietary patterns were identified. BMI and WHtR were associated with adiponectin, leptin and hs-CRP (the last, only associated with BMI). Intakes of β-carotene equivalents and vitamin C were associated with adiponectin; saturated fatty acids (SFA), vitamin A, manganese and selenium with leptin; linoleic acid with PAI-1; and oleic acid and vitamin E with IL-6. Selenium was inversely associated with adiponectin, whereas magnesium was positively associated with IL-6. MDP was associated with higher plasma concentrations of adiponectin (β=0.174, P<0.05); after adjustment for BMI, associations were not significant (β=0.144, P=0.076). WDP was negatively associated with adiponectin (β=-0.177, P<0.05) and positively with IL-6 (β=0.183, P<0.05). Subclinical inflammation is detectable with increasing BMI and also WHtR. Measures of adiposity (BMI and WHtR) are significant predictors of adiponectin, leptin and hs-CRP. Dietary patterns per se have a small role in affecting inflammatory markers among adolescents.

Regional thalamic neuropathology in patients with hippocampal sclerosis and epilepsy: A postmortem study

PubMed Central

Sinjab, Barah; Martinian, Lillian; Sisodiya, Sanjay M; Thom, Maria

2013-01-01

Purpose Clinical, experimental, and neuroimaging data all indicate that the thalamus is involved in the network of changes associated with temporal lobe epilepsy (TLE), particularly in association with hippocampal sclerosis (HS), with potential roles in seizure initiation and propagation. Pathologic changes in the thalamus may be a result of an initial insult, ongoing seizures, or retrograde degeneration through reciprocal connections between thalamic and limbic regions. Our aim was to carry out a neuropathologic analysis of the thalamus in a postmortem (PM) epilepsy series, to assess the distribution, severity, and nature of pathologic changes and its association with HS. Methods Twenty-four epilepsy PM cases (age range 25–87 years) and eight controls (age range 38–85 years) were studied. HS was classified as unilateral (UHS, 11 cases), bilateral (BHS, 4 cases) or absent (No-HS, 9 cases). Samples from the left and right sides of the thalamus were stained with cresyl violet (CV), and for glial firbillary acidic protein (GFAP) and synaptophysin. Using image analysis, neuronal densities (NDs) or field fraction staining values (GFAP, synaptophysin) were measured in four thalamic nuclei: anteroventral nucleus (AV), lateral dorsal nucleus (LD), mediodorsal nucleus (MD), and ventrolateral nucleus (VL). The results were compared within and between cases. Key Findings The severity, nature, and distribution of thalamic pathology varied between cases. A pattern that emerged was a preferential involvement of the MD in UHS cases with a reduction in mean ND ipsilateral to the side of HS (p = 0.05). In UHS cases, greater field fraction values for GFAP and lower values for synaptophysin and ND were seen in the majority of cases in the MD ipsilateral to the side of sclerosis compared to other thalamic nuclei. In addition, differences in the mean ND between classical HS, atypical HS, and No-HS cases were noted in the ipsilateral MD (p < 0.05), with lower values observed in HS. Significance Our study demonstrates that stereotypical pathologic changes, as seen in HS, are not clearly defined in the thalamus. This may be partly explained by the heterogeneity of our PM study group. With quantitation, there is some evidence for preferential involvement of the MD, suggesting a potential role in TLE, which requires further investigation. PMID:24138281

Analysis on Patterns of Globally Coupled Phase Oscillators with Attractive and Repulsive Interactions

NASA Astrophysics Data System (ADS)

Wang, Peng-Fei; Ruan, Xiao-Dong; Xu, Zhong-Bin; Fu, Xin

2015-11-01

The Hong-Strogatz (HS) model of globally coupled phase oscillators with attractive and repulsive interactions reflects the fact that each individual (oscillator) has its own attitude (attractive or repulsive) to the same environment (mean field). Previous studies on HS model focused mainly on the stable states on Ott-Antonsen (OA) manifold. In this paper, the eigenvalues of the Jacobi matrix of each fixed point in HS model are explicitly derived, with the aim to understand the local dynamics around each fixed point. Phase transitions are described according to relative population and coupling strength. Besides, the dynamics off OA manifold is studied. Supported by the National Basic Research Program of China under Grant No. 2015CB057301, the Applied Research Project of Public Welfare Technology of Zhejiang Province under Grant No. 201SC31109 and China Postdoctoral Science Foundation under Grant No. 2014M560483

Low-latitude expressions of high-latitude forcing during Heinrich Stadial 1 and the Younger Dryas in northern South America

NASA Astrophysics Data System (ADS)

Bahr, André; Hoffmann, Julia; Schönfeld, Joachim; Schmidt, Matthew W.; Nürnberg, Dirk; Batenburg, Sietske J.; Voigt, Silke

2018-01-01

Changes in Atlantic Meridional Overturning Circulation (AMOC) strength exert a major influence on global atmospheric circulation patterns. However, the pacing and mechanisms of low-latitude responses to high-latitude forcing are insufficiently constrained so far. To elucidate the interaction of atmospheric and oceanic forcing in tropical South America during periods of major AMOC reductions (Heinrich Stadial 1 and the Younger Dryas) we generated a high-resolution foraminiferal multi-proxy record from off the Orinoco River based on Ba/Ca and Mg/Ca ratios, as well as stable isotope measurements. The data clearly indicate a three-phased structure of HS1 based on the reconfiguration of ocean currents in the tropical Atlantic Ocean. The initial phase (HS1a) is characterized by a diminished North Brazil Current, a southward displacement of the ITCZ, and moist conditions dominating northeastern Brazil. During subsequent HS1b, the NBC was even more diminished or yet reversed and the ITCZ shifted to its southernmost position. Hence, dryer conditions prevailed in northern South America, while eastern Brazil experienced maximally wet conditions. During the final stage, HS1c, conditions are similar to HS1a. The YD represents a smaller amplitude version of HS1 with a southward-shifted ITCZ. Our findings imply that the low-latitude continental climate response to high-latitude forcing is mediated by reconfigurations of surface ocean currents in low latitudes. Our new records demonstrate the extreme sensitivity of the terrestrial realm in tropical South America to abrupt perturbations in oceanic circulation during periods of unstable climate conditions.

Alteration of microcirculation is a hallmark of very early systemic sclerosis patients: a laser speckle contrast analysis.

PubMed

Della Rossa, Alessandra; Cazzato, Massimiliano; d'Ascanio, Anna; Tavoni, Antonio; Bencivelli, Walter; Pepe, Pasquale; Mosca, Marta; Baldini, Chiara; Rossi, Marco; Bombardieri, Stefano

2013-01-01

To investigate blood flow and microvascular reactivity by laser speckle perfusion imager (Perimed, Jarfalla) in consecutive patients affected by Raynaud's phenomenon at baseline and following dynamic stimulations. Skin blood flow in the dorsum of the hand was measured at baseline and after cold test and post-occlusive hyperemia test in 56 consecutive subjects affected by Raynaud's phenomenon (RP), 20 primary (PRP) and 36 secondary to systemic sclerosis (SSc). Twenty healthy subjects (HS) were studied as controls. After cold test, SSc had a significant reduction of blood flow (-58%) as compared to HS (-19%) (p=0.01). Recovery time was significantly higher in SSc (58 minutes) as compared to HS (18 minutes) and PRP (19 minutes) (p=0.006 and 0.0016, respectively). Peak flow after ischaemic test was significantly reduced in SSc (+237%) as compared to PRP (+485%) (p=0.0068). Post-ischaemic hyperemic area under the curve (AUC) was blunted in SSc (79U/sec) compared to PRP (167 U/sec) (p=0.0126). Proximal distal gradient was noticed in 74% of HS, 45% of PRP and 36% of SSc (p=0.01). Homogeneous pattern of flux distribution was significantly different between HS (95%), PRP (80%), and SSc (16%) (p<0.0001). Among SSc patients, a significant difference in ischaemic challenge was shown between patients with early-SSc versus patients with definite-SSc. Our preliminary results indicate a clearcut alteration of the dynamic of microcirculation in SSc-RP as compared to PRP and HS. Among SSc patients, early-SSc is a separate entity as compared to established disease.

Lack of RAAS inhibition by high-salt intake is associated with arterial stiffness in hypertensive patients.

PubMed

Kotliar, Carol; Kempny, Pablo; Gonzalez, Sergio; Castellaro, Carlos; Forcada, Pedro; Obregon, Sebastián; Cavanagh, Elena; Chiabaut Svane, Jorge; Casarini, Maria Jesus; Rojas, Mercedes; Inserra, Felipe

2014-12-01

The relationship between salt intake, blood pressure and RAAS activation is still controversial, being that both high- and low-salt intakes are associated with cardiovascular events in a J-shaped curve pattern. We hypothesized that different patterns of RAAS response to dietary salt intake among hypertensives could be identified, while vascular damage would be related to high-salt intake plus absence of expected RAAS inhibition. We aim to assess the relationship between sodium intake, RAAS and vascular stiffness in hypertension. We screened 681 hypertensive patients for urinary/plasma electrolytes, renin, aldosterone and pulse wave velocity (PWV) under their usual salt intake level. After applying exclusion criteria, an inverse relation between urinary sodium and RAAS was observed in the 300 remaining subjects. Additionally, four types of response were identified: 1) Low (L) sodium (S)-Low RAAS, 2) LS-High (H) SRAAS, 3) HS-Low RAAS, 4) HS-High RAAS. We found no differences in age/BP among groups, but type 4 response individuals included more females and a higher pulse wave velocity. We showed a) an inverse salt-RAAS relation, b) an association between HS plus high RAAS with increased PWV that could identify a higher-risk hypertensive condition. © The Author(s) 2014.

Myopic aberrations: Simulation based comparison of curvature and Hartmann Shack wavefront sensors

NASA Astrophysics Data System (ADS)

Basavaraju, Roopashree M.; Akondi, Vyas; Weddell, Stephen J.; Budihal, Raghavendra Prasad

2014-02-01

In comparison with a Hartmann Shack wavefront sensor, the curvature wavefront sensor is known for its higher sensitivity and greater dynamic range. The aim of this study is to numerically investigate the merits of using a curvature wavefront sensor, in comparison with a Hartmann Shack (HS) wavefront sensor, to analyze aberrations of the myopic eye. Aberrations were statistically generated using Zernike coefficient data of 41 myopic subjects obtained from the literature. The curvature sensor is relatively simple to implement, and the processing of extra- and intra-focal images was linearly resolved using the Radon transform to provide Zernike modes corresponding to statistically generated aberrations. Simulations of the HS wavefront sensor involve the evaluation of the focal spot pattern from simulated aberrations. Optical wavefronts were reconstructed using the slope geometry of Southwell. Monte Carlo simulation was used to find critical parameters for accurate wavefront sensing and to investigate the performance of HS and curvature sensors. The performance of the HS sensor is highly dependent on the number of subapertures and the curvature sensor is largely dependent on the number of Zernike modes used to represent the aberration and the effective propagation distance. It is shown that in order to achieve high wavefront sensing accuracy while measuring aberrations of the myopic eye, a simpler and cost effective curvature wavefront sensor is a reliable alternative to a high resolution HS wavefront sensor with a large number of subapertures.

Development and Performance of the ACTS High Speed VSAT

NASA Technical Reports Server (NTRS)

Quintana, J.; Tran, Q.; Dendy, R.

1999-01-01

The Advanced Communication Technology Satellite (ACTS), developed by the U.S. National Aeronautics and Space Administration (NASA) has demonstrated the breakthrough technologies of Ka-band, spot beam antennas, and on-board processing. These technologies have enabled the development of very small aperture terminals (VSAT) and ultra-small aperture terminals (USAT) which have capabilities greater than were previously possible with conventional satellite technologies. However, the ACTS baseband processor (BBP) is designed using a time division multiple access (TDMA) scheme, which requires each earth station using the BBP to transmit data at a burst rate which is much higher than the user throughput data rate. This tends to mitigate the advantage of the new technologies by requiring a larger earth station antenna and/or a higher-powered uplink amplifier than would be necessary for a continuous transmission at the user data rate. Conversely, the user data rate is much less than the rate that can be supported by the antenna size and amplifier. For example, the ACTS TI VSAT operates at a burst rate of 27.5 Mbps, but the maximum user data rate is 1.792 Mbps. The throughput efficiency is slightly more than 6.5%. For an operational network, this level of overhead will greatly increase the cost of the user earth stations, and that increased cost must be repeated thousands of times, which may ultimately reduce the market for such a system. The ACTS High Speed VSAT (HS VSAT) is an effort to experimentally demonstrate the maximum user throughput data rate which can be achieved using the technologies developed and implemented on ACTS. Specifically, this was done by operating the system uplinks as frequency division multiple access (FDMA), essentially assigning all available TDMA time slots to a single user on each of two uplink frequencies. Preliminary results show that using a 1.2-m antenna in this mode, the HS VSAT can achieve between 22 and 24 Mbps out of the 27.5 Mbps burst rate, for a throughput efficiency of 80-88%. This paper describes the modifications made to the TI VSAT to enable it to operate at high speed, including hardware considerations, interface modifications, and software modifications. In addition, it describes the results of NASA HS VSAT experiments, continuing work on an improved user interface, and plans for future experiments.

Single Stage Tandem Mass Spectrometry Assignment of the C-5 Uronic Acid Stereochemistry in Heparan Sulfate Tetrasaccharides using Electron Detachment Dissociation

NASA Astrophysics Data System (ADS)

Agyekum, Isaac; Zong, Chengli; Boons, Geert-Jan; Amster, I. Jonathan

2017-09-01

The analysis of heparan sulfate (HS) glycosaminoglycans presents many challenges, due to the high degree of structural heterogeneity arising from their non-template biosynthesis. Complete structural elucidation of glycosaminoglycans necessitates the unambiguous assignments of sulfo modifications and the C-5 uronic acid stereochemistry. Efforts to develop tandem mass spectrometric-based methods for the structural analysis of glycosaminoglycans have focused on the assignment of sulfo positions. The present work focuses on the assignment of the C-5 stereochemistry of the uronic acid that lies closest to the reducing end. Prior work with electron-based tandem mass spectrometry methods, specifically electron detachment dissociation (EDD), have shown great promise in providing stereo-specific product ions, such as the B3 ´ -CO2, which has been found to distinguish glucuronic acid (GlcA) from iduronic acid (IdoA) in some HS tetrasaccharides. The previously observed diagnostic ions are generally not observed with 2- O-sulfo uronic acids or for more highly sulfated heparan sulfate tetrasaccharides. A recent study using electron detachment dissociation and principal component analysis revealed a series of ions that correlate with GlcA versus IdoA for a set of 2- O-sulfo HS tetrasaccharide standards. The present work comprehensively investigates the efficacy of these ions for assigning the C-5 stereochemistry of the reducing end uronic acid in 33 HS tetrasaccharides. A diagnostic ratio can be computed from the sum of the ions that correlate to GlcA to those that correlate to IdoA. [Figure not available: see fulltext.

Design of a versatile clinical aberrometer

NASA Astrophysics Data System (ADS)

Sheehan, Matthew; Goncharov, Alexander; Dainty, Chris

2005-09-01

We have designed an ocular aberrometer based on the Hartmann-Shack (HS) type wavefront sensor for use in optometry clinics. The optical system has enhanced versatility compared with commercial aberrometers, yet it is compact and user-friendly. The system has the capability to sense both on-axis and off-axis aberrations in the eye within an unobstructed 20 degree field. This capability is essential to collect population data for off-axis aberrations. This data will be useful in designing future adaptive optics (AO) systems to improve image quality of eccentric retinal areas, in particular, for multi-conjugate AO systems. The ability of the examiner to control the accommodation demand is a unique feature of the design that commercial instruments are capable of only after modification. The pupil alignment channel is re-combined with the sensing channel in a parallel path and imaged on a single CCD. This makes the instrument more compact, less expensive, and it helps to synchronize the pupil center with the HS spot coordinate system. Another advantage of the optical design is telecentric re-imaging of the HS spots, increasing the robustness to small longitudinal alignment errors. The optical system has been optimized with a ray-tracing program and its prototype is being constructed. Design considerations together with a description of the optical components are presented. Difficulties and future work are outlined.

Automatic moment segmentation and peak detection analysis of heart sound pattern via short-time modified Hilbert transform.

PubMed

Sun, Shuping; Jiang, Zhongwei; Wang, Haibin; Fang, Yu

2014-05-01

This paper proposes a novel automatic method for the moment segmentation and peak detection analysis of heart sound (HS) pattern, with special attention to the characteristics of the envelopes of HS and considering the properties of the Hilbert transform (HT). The moment segmentation and peak location are accomplished in two steps. First, by applying the Viola integral waveform method in the time domain, the envelope (E(T)) of the HS signal is obtained with an emphasis on the first heart sound (S1) and the second heart sound (S2). Then, based on the characteristics of the E(T) and the properties of the HT of the convex and concave functions, a novel method, the short-time modified Hilbert transform (STMHT), is proposed to automatically locate the moment segmentation and peak points for the HS by the zero crossing points of the STMHT. A fast algorithm for calculating the STMHT of E(T) can be expressed by multiplying the E(T) by an equivalent window (W(E)). According to the range of heart beats and based on the numerical experiments and the important parameters of the STMHT, a moving window width of N=1s is validated for locating the moment segmentation and peak points for HS. The proposed moment segmentation and peak location procedure method is validated by sounds from Michigan HS database and sounds from clinical heart diseases, such as a ventricular septal defect (VSD), an aortic septal defect (ASD), Tetralogy of Fallot (TOF), rheumatic heart disease (RHD), and so on. As a result, for the sounds where S2 can be separated from S1, the average accuracies achieved for the peak of S1 (AP₁), the peak of S2 (AP₂), the moment segmentation points from S1 to S2 (AT₁₂) and the cardiac cycle (ACC) are 98.53%, 98.31% and 98.36% and 97.37%, respectively. For the sounds where S1 cannot be separated from S2, the average accuracies achieved for the peak of S1 and S2 (AP₁₂) and the cardiac cycle ACC are 100% and 96.69%. Copyright © 2014 Elsevier Ireland Ltd. All rights reserved.

Compressive hyperspectral and multispectral imaging fusion

NASA Astrophysics Data System (ADS)

Espitia, Óscar; Castillo, Sergio; Arguello, Henry

2016-05-01

Image fusion is a valuable framework which combines two or more images of the same scene from one or multiple sensors, allowing to improve the resolution of the images and increase the interpretable content. In remote sensing a common fusion problem consists of merging hyperspectral (HS) and multispectral (MS) images that involve large amount of redundant data, which ignores the highly correlated structure of the datacube along the spatial and spectral dimensions. Compressive HS and MS systems compress the spectral data in the acquisition step allowing to reduce the data redundancy by using different sampling patterns. This work presents a compressed HS and MS image fusion approach, which uses a high dimensional joint sparse model. The joint sparse model is formulated by combining HS and MS compressive acquisition models. The high spectral and spatial resolution image is reconstructed by using sparse optimization algorithms. Different fusion spectral image scenarios are used to explore the performance of the proposed scheme. Several simulations with synthetic and real datacubes show promising results as the reliable reconstruction of a high spectral and spatial resolution image can be achieved by using as few as just the 50% of the datacube.

Development of "material-specific" hemispheric specialization from beginning to end.

PubMed

Gingras, Benjamin; Braun, Claude M J

2018-07-01

Disparity of verbal and performance intelligence (VIQ, PIQ) on the Wechsler scales of intelligence is a conceptually cluttered and empirically weak measure of hemispheric specialization (HS). However, in the context of life span research, it is the only measure that can be exploited meta-analytically with the lesion method from prenatal life to late senescence. We assembled 1917 cases with a unilateral cortical focal brain lesion occurring at all ages and a post-lesion VIQ and PIQ. Lesion locus, volume and side were documented for each case, as well as age at lesion onset, age at first symptoms and age at the IQ test, presence/absence of epilepsy, lesion aetiology, gender, date of publication or of transfer of medical file. With and without covariate adjustment, HS was significant across the life span though its pattern changed. HS increased linearly and highly significantly until late senescence. Only in early adulthood did VIQ appear to vacate the right temporal lobe and occupy the left and PIQ vacate the left parietal lobe and occupy the right until late senescence. Biomaturational factors are more important in the ontogeny of material-specific HS over the whole life span than previously established.

Cognitive, cultural, and linguistic sources of a handshape distinction expressing agentivity.

PubMed

Brentari, Diane; Di Renzo, Alessio; Keane, Jonathan; Volterra, Virginia

2015-01-01

In this paper the cognitive, cultural, and linguistic bases for a pattern of conventionalization of two types of iconic handshapes are described. Work on sign languages has shown that handling handshapes (H-HSs: those that represent how objects are handled or manipulated) and object handshapes (O-HSs: those that represent the class, size, or shape of objects) express an agentive/non-agentive semantic distinction in many sign languages. H-HSs are used in agentive event descriptions and O-HSs are used in non-agentive event descriptions. In this work, American Sign Language (ASL) and Italian Sign Language (LIS) productions are compared (adults and children) as well as the corresponding groups of gesturers in each country using "silent gesture." While the gesture groups, in general, did not employ an H-HS/O-HS distinction, all participants (signers and gesturers) used iconic handshapes (H-HSs and O-HSs together) more often in agentive than in no-agent event descriptions; moreover, none of the subjects produced an opposite pattern than the expected one (i.e., H-HSs associated with no-agent descriptions and O-HSs associated with agentive ones). These effects are argued to be grounded in cognition. In addition, some individual gesturers were observed to produce the H-HS/O-HS opposition for agentive and non-agentive event descriptions-that is, more Italian than American adult gesturers. This effect is argued to be grounded in culture. Finally, the agentive/non-agentive handshape opposition is confirmed for signers of ASL and LIS, but previously unreported cross-linguistic differences were also found across both adult and child sign groups. It is, therefore, concluded that cognitive, cultural, and linguistic factors contribute to the conventionalization of this distinction of handshape type. Copyright © 2014 Cognitive Science Society, Inc.

Expression of HSPs: an adaptive mechanism during long-term heat stress in goats ( Capra hircus)

NASA Astrophysics Data System (ADS)

Dangi, Satyaveer Singh; Gupta, Mahesh; Dangi, Saroj K.; Chouhan, Vikrant Singh; Maurya, V. P.; Kumar, Puneet; Singh, Gyanendra; Sarkar, Mihir

2015-08-01

Menacing global rise in surface temperature compelled more focus of research over understanding heat stress response mechanism of animals and mitigation of heat stress. Twenty-four goats divided into four groups ( n = 6) such as NHS (non-heat-stressed), HS (heat-stressed), HS + VC (heat-stressed administered with vitamin C), and HS + VE + Se (heat-stressed administered with vitamin E and selenium). Except NHS group, other groups were exposed to repeated heat stress (42 °C) for 6 h on 16 consecutive days. Blood samples were collected at the end of heat exposure on days 1, 6, 11, and 16. When groups compared between days, expression of all heat shock proteins (HSPs) showed a similar pattern as first peak on day 1, reached to basal level on the sixth day, and followed by second peak on day 16. The relative messenger RNA (mRNA) and protein expression of HSP 60, HSP70, and HSP90 was observed highest ( P < 0.05) in HS group, followed by antioxidant-administered group on days 1 and 16, which signifies that antioxidants have dampening effect on HSP expression. HSP105/110 expression was highest ( P < 0.05) on day 16. We conclude that HSP expression pattern is at least two-peak phenomenon, i.e., primary window of HSP protection on the first day followed by second window of protection on day 16. HSP60, HSP70, and HSP90 play an important role during the initial phase of heat stress acclimation whereas HSP105/110 joins this cascade at later phase. Antioxidants may possibly attenuate the HSP expression by reducing the oxidative stress.

Mediterranean dietary pattern adherence: associations with prediabetes, metabolic syndrome, and related microinflammation.

PubMed

Viscogliosi, Giovanni; Cipriani, Elisa; Liguori, Maria Livia; Marigliano, Benedetta; Saliola, Mirella; Ettorre, Evaristo; Andreozzi, Paola

2013-06-01

The adherence to the Mediterranean Diet (Med Diet) seems to reduce the incidence of metabolic syndrome. The present study aimed to explore whether the adherence to the overall Med Diet pattern and to specific Med Diet items is associated with the presence of metabolic syndrome, impaired fasting glucose (IFG), insulin resistance (IR), and microinflammation in subjects free of diabetes and cardiovascular diseases. Each patient underwent clinical assessment. Adherence to the Med Diet was measured by a previously validated 14-item questionnaire. Metabolic syndrome was defined by the National Cholesterol Education Program Adult Treatment Panel III (NCEP ATP III) criteria; IR was defined by homeostasis model assessment of insulin resistance (HOMA-IR); inflammation was assessed through a high-sensitivity C-reactive protein (hsCRP) assay. A total of 120 subjects (64.2% women, mean age 59.8±10.2 years) were enrolled at this study. Subjects with lower Med Diet pattern adherence exhibited higher occurrence of metabolic syndrome and all its components and higher HOMA-IR and hsCRP values (P for all <0.0001). Subjects with metabolic syndrome were less likely to consume olive oil (P=0.002) and vegetables (P=0.023). By multivariable analyses, the overall Med Diet score was found to be strongly and inversely associated with the presence of metabolic syndrome [B=-0.066; 95% confidence interval (CI) -0.105 to -0.028; P=0.001], IFG (B=-0.076; 95% CI -0.114 to -0.038; p<0.0001), high HOMA-IR (B=-0.071; 95% CI -0.108 to -0.034; P<0.0001) and high hsCRP (B=-0.082; 95% CI -0.125 to -0.045; P<0.0001). None of specific Med Diet items independently predicted metabolic syndrome, IFG, and high HOMA-IR. Instead, the consumption of white meat over red meat (B=-0.324; 95% CI -0.467 to -0.178; P<0.0001) was found to be inversely associated with increased hsCRP. The inverse associations between adherence to Med Diet and the prevalence of metabolic syndrome and prediabetes may be due more to the effects of the entire dietary pattern rather than to individual food components. Metabolic syndrome-related microinflammation may further be linked to specific Med Diet components.

Caspase-1 Is Hepatoprotective during Trauma and Hemorrhagic Shock by Reducing Liver Injury and Inflammation

PubMed Central

Menzel, Christoph L; Sun, Qian; Loughran, Patricia A; Pape, Hans-Christoph; Billiar, Timothy R; Scott, Melanie J

2011-01-01

Adaptive immune responses are induced in liver after major stresses such as hemorrhagic shock (HS) and trauma. There is emerging evidence that the inflammasome, the multiprotein platform that induces caspase-1 activation and promotes interleukin (IL)-1β and IL-18 processing, is activated in response to cellular oxidative stress, such as after hypoxia, ischemia and HS. Additionally, damage-associated molecular patterns, such as those released after injury, have been shown to activate the inflammasome and caspase-1 through the NOD-like receptor (NLR) NLRP3. However, the role of the inflammasome in organ injury after HS and trauma is unknown. We therefore investigated inflammatory responses and end-organ injury in wild-type (WT) and caspase-1−/−mice in our model of HS with bilateral femur fracture (HS/BFF). We found that caspase-1−/− mice had higher levels of systemic inflammatory cytokines than WT mice. This result corresponded to higher levels of liver damage, cell death and neutrophil influx in caspase-1−/− liver compared with WT, although there was no difference in lung damage between experimental groups. To determine if hepatoprotection also depended on NLRP3, we subjected NLRP3−/− mice to HS/BFF, but found inflammatory responses and liver damage in these mice was similar to WT. Hepatoprotection was also not due to caspase-1–dependent cytokines, IL-1β and IL-18. Altogether, these data suggest that caspase-1 is hepatoprotective, in part through regulation of cell death pathways in the liver after major trauma, and that caspase-1 activation after HS/BFF does not depend on NLRP3. These findings may have implications for the treatment of trauma patients and may lead to progress in prevention or treatment of multiple organ failure (MOF). PMID:21666957

Penta- and tetracarbonyls of Ru, Os, and Hs: Electronic structure, bonding, and volatility

NASA Astrophysics Data System (ADS)

Pershina, V.; Iliaš, M.

2017-05-01

Calculations of the electronic structures and properties of M(CO)5 and M(CO)4, where M = Ru, Os, and Hs, have been performed using a variety of relativistic methods such as density functional theory and Dirac-Coulomb correlated ones implemented in program packages such as ADF, DIRAC, and ReSpect. The obtained results show that trends in spectroscopic properties of the M(CO)5 species in group 8 follow the same pattern as that of other compounds of group 4 through group 8 elements. The calculated first M-CO bond dissociation energy (FBDE) of Hs(CO)5 turned out to be significantly weaker than that of Os(CO)5. This was obtained both at the scalar relativistic and spin-orbit levels of theory. The reason for that is the relativistic destabilization and the expansion of the 6d AOs, responsible for weaker σ-forth and π-back donations in the Hs compound. Thus, the FBDEs of M(CO)5 have a Λ-shape behavior in the row Ru-Os-Hs. The non-relativistic FBDEs steadily increase in this row. Using the results of the molecular calculations and a molecule-slab dispersion interaction model, the volatility of the group-8 carbonyls was estimated as adsorption enthalpies, ΔHads, on surfaces of quartz and Teflon used in gas-phase chromatography experiments. It was found that Hs(CO)5 should be almost as volatile as the homologs; however, its interaction strength with these surfaces should be somewhat larger than that of both Ru(CO)5 and Os(CO)5, while the M(CO)4 (M = Ru, Os, and Hs) molecules should be non-volatile. It will, therefore, be difficult to distinguish between group-8 M(CO)5 species by measurements of their volatility as ΔHads on inert surfaces with error bars of ˜4 kJ/mol.

Heterogeneous Stock Rat: A Unique Animal Model for Mapping Genes Influencing Bone Fragility

PubMed Central

Alam, Imranul; Koller, Daniel L.; Sun, Qiwei; Roeder, Ryan K.; Cañete, Toni; Blázquez, Gloria; López-Aumatell, Regina; Martínez-Membrives, Esther; Vicens-Costa, Elia; Mont, Carme; Díaz, Sira; Tobeña, Adolf; Fernández-Teruel, Alberto; Whitley, Adam; Strid, Pernilla; Diez, Margarita; Johannesson, Martina; Flint, Jonathan; Econs, Michael J.; Turner, Charles H.; Foroud, Tatiana

2011-01-01

Previously, we demonstrated that skeletal mass, structure and biomechanical properties vary considerably among 11 different inbred rat strains. Subsequently, we performed quantitative trait loci (QTL) analysis in 4 inbred rat strains (F344, LEW, COP and DA) for different bone phenotypes and identified several candidate genes influencing various bone traits. The standard approach to narrowing QTL intervals down to a few candidate genes typically employs the generation of congenic lines, which is time consuming and often not successful. A potential alternative approach is to use a highly genetically informative animal model resource capable of delivering very high-resolution gene mapping such as Heterogeneous stock (HS) rat. HS rat was derived from eight inbred progenitors: ACI/N, BN/SsN, BUF/N, F344/N, M520/N, MR/N, WKY/N and WN/N. The genetic recombination pattern generated across 50 generations in these rats has been shown to deliver ultra-high even gene-level resolution for complex genetic studies. The purpose of this study is to investigate the usefulness of the HS rat model for fine mapping and identification of genes underlying bone fragility phenotypes. We compared bone geometry, density and strength phenotypes at multiple skeletal sites in HS rats with those obtained from 5 of the 8 progenitor inbred strains. In addition, we estimated the heritability for different bone phenotypes in these rats and employed principal component analysis to explore relationships among bone phenotypes in the HS rats. Our study demonstrates that significant variability exists for different skeletal phenotypes in HS rats compared with their inbred progenitors. In addition, we estimated high heritability for several bone phenotypes and biologically interpretable factors explaining significant overall variability, suggesting that the HS rat model could be a unique genetic resource for rapid and efficient discovery of the genetic determinants of bone fragility. PMID:21334473

Heterogeneous stock rat: a unique animal model for mapping genes influencing bone fragility.

PubMed

Alam, Imranul; Koller, Daniel L; Sun, Qiwei; Roeder, Ryan K; Cañete, Toni; Blázquez, Gloria; López-Aumatell, Regina; Martínez-Membrives, Esther; Vicens-Costa, Elia; Mont, Carme; Díaz, Sira; Tobeña, Adolf; Fernández-Teruel, Alberto; Whitley, Adam; Strid, Pernilla; Diez, Margarita; Johannesson, Martina; Flint, Jonathan; Econs, Michael J; Turner, Charles H; Foroud, Tatiana

2011-05-01

Previously, we demonstrated that skeletal mass, structure and biomechanical properties vary considerably among 11 different inbred rat strains. Subsequently, we performed quantitative trait loci (QTL) analysis in four inbred rat strains (F344, LEW, COP and DA) for different bone phenotypes and identified several candidate genes influencing various bone traits. The standard approach to narrowing QTL intervals down to a few candidate genes typically employs the generation of congenic lines, which is time consuming and often not successful. A potential alternative approach is to use a highly genetically informative animal model resource capable of delivering very high resolution gene mapping such as Heterogeneous stock (HS) rat. HS rat was derived from eight inbred progenitors: ACI/N, BN/SsN, BUF/N, F344/N, M520/N, MR/N, WKY/N and WN/N. The genetic recombination pattern generated across 50 generations in these rats has been shown to deliver ultra-high even gene-level resolution for complex genetic studies. The purpose of this study is to investigate the usefulness of the HS rat model for fine mapping and identification of genes underlying bone fragility phenotypes. We compared bone geometry, density and strength phenotypes at multiple skeletal sites in HS rats with those obtained from five of the eight progenitor inbred strains. In addition, we estimated the heritability for different bone phenotypes in these rats and employed principal component analysis to explore relationships among bone phenotypes in the HS rats. Our study demonstrates that significant variability exists for different skeletal phenotypes in HS rats compared with their inbred progenitors. In addition, we estimated high heritability for several bone phenotypes and biologically interpretable factors explaining significant overall variability, suggesting that the HS rat model could be a unique genetic resource for rapid and efficient discovery of the genetic determinants of bone fragility. Copyright © 2010 Elsevier Inc. All rights reserved.

DNaseI Hypersensitivity and Ultraconservation Reveal Novel, Interdependent Long-Range Enhancers at the Complex Pax6 Cis-Regulatory Region

PubMed Central

McBride, David J.; Buckle, Adam; van Heyningen, Veronica; Kleinjan, Dirk A.

2011-01-01

The PAX6 gene plays a crucial role in development of the eye, brain, olfactory system and endocrine pancreas. Consistent with its pleiotropic role the gene exhibits a complex developmental expression pattern which is subject to strict spatial, temporal and quantitative regulation. Control of expression depends on a large array of cis-elements residing in an extended genomic domain around the coding region of the gene. The minimal essential region required for proper regulation of this complex locus has been defined through analysis of human aniridia-associated breakpoints and YAC transgenic rescue studies of the mouse smalleye mutant. We have carried out a systematic DNase I hypersensitive site (HS) analysis across 200 kb of this critical region of mouse chromosome 2E3 to identify putative regulatory elements. Mapping the identified HSs onto a percent identity plot (PIP) shows many HSs correspond to recognisable genomic features such as evolutionarily conserved sequences, CpG islands and retrotransposon derived repeats. We then focussed on a region previously shown to contain essential long range cis-regulatory information, the Pax6 downstream regulatory region (DRR), allowing comparison of mouse HS data with previous human HS data for this region. Reporter transgenic mice for two of the HS sites, HS5 and HS6, show that they function as tissue specific regulatory elements. In addition we have characterised enhancer activity of an ultra-conserved cis-regulatory region located near Pax6, termed E60. All three cis-elements exhibit multiple spatio-temporal activities in the embryo that overlap between themselves and other elements in the locus. Using a deletion set of YAC reporter transgenic mice we demonstrate functional interdependence of the elements. Finally, we use the HS6 enhancer as a marker for the migration of precerebellar neuro-epithelium cells to the hindbrain precerebellar nuclei along the posterior and anterior extramural streams allowing visualisation of migratory defects in both pathways in Pax6Sey/Sey mice. PMID:22220192

Computer-assisted liver graft steatosis assessment via learning-based texture analysis.

PubMed

Moccia, Sara; Mattos, Leonardo S; Patrini, Ilaria; Ruperti, Michela; Poté, Nicolas; Dondero, Federica; Cauchy, François; Sepulveda, Ailton; Soubrane, Olivier; De Momi, Elena; Diaspro, Alberto; Cesaretti, Manuela

2018-05-23

Fast and accurate graft hepatic steatosis (HS) assessment is of primary importance for lowering liver dysfunction risks after transplantation. Histopathological analysis of biopsied liver is the gold standard for assessing HS, despite being invasive and time consuming. Due to the short time availability between liver procurement and transplantation, surgeons perform HS assessment through clinical evaluation (medical history, blood tests) and liver texture visual analysis. Despite visual analysis being recognized as challenging in the clinical literature, few efforts have been invested to develop computer-assisted solutions for HS assessment. The objective of this paper is to investigate the automatic analysis of liver texture with machine learning algorithms to automate the HS assessment process and offer support for the surgeon decision process. Forty RGB images of forty different donors were analyzed. The images were captured with an RGB smartphone camera in the operating room (OR). Twenty images refer to livers that were accepted and 20 to discarded livers. Fifteen randomly selected liver patches were extracted from each image. Patch size was [Formula: see text]. This way, a balanced dataset of 600 patches was obtained. Intensity-based features (INT), histogram of local binary pattern ([Formula: see text]), and gray-level co-occurrence matrix ([Formula: see text]) were investigated. Blood-sample features (Blo) were included in the analysis, too. Supervised and semisupervised learning approaches were investigated for feature classification. The leave-one-patient-out cross-validation was performed to estimate the classification performance. With the best-performing feature set ([Formula: see text]) and semisupervised learning, the achieved classification sensitivity, specificity, and accuracy were 95, 81, and 88%, respectively. This research represents the first attempt to use machine learning and automatic texture analysis of RGB images from ubiquitous smartphone cameras for the task of graft HS assessment. The results suggest that is a promising strategy to develop a fully automatic solution to assist surgeons in HS assessment inside the OR.

Impact of hippocampal subfield histopathology in episodic memory impairment in mesial temporal lobe epilepsy and hippocampal sclerosis.

PubMed

Comper, Sandra Mara; Jardim, Anaclara Prada; Corso, Jeana Torres; Gaça, Larissa Botelho; Noffs, Maria Helena Silva; Lancellotti, Carmen Lúcia Penteado; Cavalheiro, Esper Abrão; Centeno, Ricardo Silva; Yacubian, Elza Márcia Targas

2017-10-01

The objective of the study was to analyze preoperative visual and verbal episodic memories in a homogeneous series of patients with mesial temporal lobe epilepsy (MTLE) and unilateral hippocampal sclerosis (HS) submitted to corticoamygdalohippocampectomy and its association with neuronal cell density of each hippocampal subfield. The hippocampi of 72 right-handed patients were collected and prepared for histopathological examination. Hippocampal sclerosis patterns were determined, and neuronal cell density was calculated. Preoperatively, two verbal and two visual memory tests (immediate and delayed recalls) were applied, and patients were divided into two groups, left and right MTLE (36/36). There were no statistical differences between groups regarding demographic and clinical data. Cornu Ammonis 4 (CA4) neuronal density was significantly lower in the right hippocampus compared with the left (p=0.048). The groups with HS presented different memory performance - the right HS were worse in visual memory test [Complex Rey Figure, immediate (p=0.001) and delayed (p=0.009)], but better in one verbal task [RAVLT delayed (p=0.005)]. Multiple regression analysis suggested that the verbal memory performance of the group with left HS was explained by CA1 neuronal density since both tasks were significantly influenced by CA1 [Logical Memory immediate recall (p=0.050) and Logical Memory and RAVLT delayed recalls (p=0.004 and p=0.001, respectively)]. For patients with right HS, both CA1 subfield integrity (p=0.006) and epilepsy duration (p=0.012) explained Complex Rey Figure immediate recall performance. Ultimately, epilepsy duration also explained the performance in the Complex Rey Figure delayed recall (p<0.001). Cornu Ammonis 1 (CA1) hippocampal subfield was related to immediate and delayed recalls of verbal memory tests in left HS, while CA1 and epilepsy duration were associated with visual memory performance in patients with right HS. Copyright © 2017 Elsevier Inc. All rights reserved.

Biogeochemical Activity of Siderophilic Cyanobacteria: Implications for Paleobiogeochemistry

NASA Technical Reports Server (NTRS)

Brown, Igor I.; Sarkisova, Svetlana A.; Auyeung, Weng S.; Garrison, Dan; Allen, Carlton C.; McKay, David S.

2007-01-01

Understanding the patterns of iron oxidation by cyanobacteria (CB) has tremendous importance for paleobiogeochemistry, since cyanobacteria are presumed to have been involved in the global oxidation of ferrous iron during the Precambrian (Cloud, 1973). B.K. Pierson (1999, 2000) first proposed to study iron deposition in iron-depositing hot springs (ID HS) as a model for Precambrian Fe(2+) oxidation. However, neither the iron-dependent physiology of individual species of CB inhabiting iron-depositing hot springs nor their interactions with minerals enriched with iron have been examined thoroughly. Such study could shed light on ancient iron turnover. Cyanobacterial species isolated from ID HS demonstrate elevated tolerance to colloidal Fe(3+) (= 1 mM), while a concentration of 0.4 mM proved toxic for mesophilic Synechocystis PCC 6803. Isolates from ID HS require 0.4-0.6 mM Fe3+ for maximal growth while the iron requirement for Synechocystis is approximately one order of magnitude lower. We have also demonstrated that thick polysaccharide sheaths around cells of CB isolated from ID HS serve as repositories for precipitated iron. The growth of the mesophilic cyanobacteria Phromidium aa in iron-saturated (0.6 mM) DH medium did not lead to iron precipitation on its filament surfaces. However, a 14.3 fil.2 culture, isolated from an ID HS and incubated under the same conditions, was covered with dense layer of precipitated iron. Our results, taken together with Pierson s data concerning the ability of Fe2+ to stimulate photosynthesis in natural CB mats in ID HS, suggest that CB inhabiting ID HS may constitute a new group of the extremophiles - siderophilic CB. Our recent experiments have revealed for the first time that CB isolates from ID HS are also capable of biodeterioration - the etching of minerals, in particular glasses enriched with Fe, Al, Ti, O, and Si. Thus, Precambrian siderophilic cyanobacteria and their predecessors could have been involved not only in iron deposition but also in the global release of elements. The ability of siderophilic CB to participate in iron turnover make them appropriate candidates for biotechnological processes.

Targeting Heparan Sulfate Proteoglycans and their Modifying Enzymes to Enhance Anticancer Chemotherapy Efficacy and Overcome Drug Resistance.

PubMed

Lanzi, Cinzia; Zaffaroni, Nadia; Cassinelli, Giuliana

2017-01-01

Targeting heparan sulfate proteoglycans (HSPGs) and enzymes involved in heparan sulfate (HS) chain editing is emerging as a new anticancer strategy. The involvement of HSPGs in tumor cell signaling, inflammation, angiogenesis and metastasis indicates that agents able to inhibit aberrant HSPG functions can potentially act as multitarget drugs affecting both tumor cell growth and the supportive boost provided by the microenvironment. Moreover, accumulating evidence supports that an altered expression or function of HSPGs, or of the complex enzyme system regulating their activities, can also depress the tumor response to anticancer treatments in several tumor types. Thereby, targeting HSPGs or HSPG modifying enzymes appears an appealing approach to enhance chemotherapy efficacy. A great deal of effort from academia and industry has led to the development of agents mimicking HS, and/or inhibiting HSPG modifying enzymes. Inhibitors of Sulf-2, an endosulfatase that edits the HS sulfation pattern, and inhibitors of heparanase, the endoglycosidase that produces functional HS fragments, appear particularly promising. In fact, a Sulf-2 inhibitor (OKN-007), and two heparanase inhibitors/HS mimics (roneparstat, PG545) are currently under early clinical investigation. In this review, we summarized preclinical studies in experimental tumor models of the main chemical classes of Sulf-2 and heparanase inhibitors. We described examples of different mechanisms through which heparanase and HSPGs, often in cooperation, may impact tumor sensitivity to various antitumor agents. Finally, we reported a few preclinical studies showing increased antitumor efficacy obtained with the use of candidate clinical HS mimics in combination regimens. Copyright© Bentham Science Publishers; For any queries, please email at epub@benthamscience.org.

Imaging of patients with hippocampal sclerosis at 7 Tesla: initial results.

PubMed

Breyer, Tobias; Wanke, Isabel; Maderwald, Stefan; Woermann, Friedrich G; Kraff, Oliver; Theysohn, Jens M; Ebner, Alois; Forsting, Michael; Ladd, Mark E; Schlamann, Marc

2010-04-01

Focal epilepsies potentially can be cured by neurosurgery; other treatment options usually remain symptomatic. High-resolution magnetic resonance (MR) imaging is the central imaging strategy in the evaluation of focal epilepsy. The most common substrate of temporal epilepsies is hippocampal sclerosis (HS), which cannot always be sufficiently characterized with current MR field strengths. Therefore, the purpose of our study was to demonstrate the feasibility of high-resolution MR imaging at 7 Tesla in patients with focal epilepsy resulting from a HS and to improve image resolution at 7 Tesla in patients with HS. Six patients with known HS were investigated with T1-, T2-, T2(*)-, and fluid-attenuated inversion recovery-weighted sequences at 7 Tesla with an eight-channel transmit-receive head coil. Total imaging time did not exceed 90 minutes per patient. High-resolution imaging at 7 Tesla is feasible and reveals high resolution of intrahippocampal structures in vivo. HS was confirmed in all patients. The maximum non-interpolated in-plane resolution reached 0.2 x 0.2 mm(2) in T2(*)-weighted images. The increased susceptibility effects at 7 Tesla revealed identification of intrahippocampal structures in more detail than at 1.5 Tesla, but otherwise led to stronger artifacts. Imaging revealed regional differences in hippocampal atrophy between patients. The scan volume was limited because of specific absorption rate restrictions, scanning time was reasonable. High-resolution imaging at 7 Tesla is promising in presurgical epilepsy imaging. "New" contrasts may further improve detection of even very small intrahippocampal structural changes. Therefore, further investigations will be necessary to demonstrate the potential benefit for presurgical selection of patients with various lesion patterns in mesial temporal epilepsies resulting from a unilateral HS. Copyright 2010 AUR. Published by Elsevier Inc. All rights reserved.

Sedentary Lifestyle and High-Carbohydrate Intake are Associated with Low-Grade Chronic Inflammation in Post-Menopause: A Cross-sectional Study.

PubMed

Alves, Bruna Cherubini; Silva, Thaís Rasia da; Spritzer, Poli Mara

2016-07-01

Introduction Cardiovascular disease (CVD) is the leading cause of death in post menopausal women, and inflammation is involved in the atherosclerosis process. Purpose to assess whether dietary pattern, metabolic profile, body composition and physical activity are associated with low-grade chronic inflammation according to high-sensitivity C-reactive protein (hs-CRP) levels in postmenopausal women. Methods ninety-five postmenopausal participants, with no evidence of clinical disease, underwent anthropometric, metabolic and hormonal assessments. Usual dietary intake was assessed with a validated food frequency questionnaire, habitual physical activity was measured with a digital pedometer, and body composition was estimated by bioelectrical impedance analysis. Patients with hs-CRP ≥10 mg/L or using hormone therapy in the last three months before the study were excluded from the analysis. Participants were stratified according to hs-CRP lower or ≥3 mg/L. Sedentary lifestyle was defined as walking fewer than 6 thousand steps a day. Two-tailed Student's t-test, Wilcoxon-Mann-Whitney U or Chi-square (χ(2)) test were used to compare differences between groups. A logistic regression model was used to estimate the odds ratio of variables for high hs-CRP. Results participants with hs-CRP ≥3 mg/L had higher body mass index (BMI), body fat percentage, waist circumference (WC), triglycerides, glucose, and homeostasis model assessment of insulin resistance (HOMA-IR) (p = 0.01 for all variables) than women with hs-CRP <3 mg/L. Also, women with hs-CRP ≥3 mg/L had a higher glycemic load diet and lower protein intake. Prevalence of sedentary lifestyle (p < 0.01) and metabolic syndrome (p < 0.01) was higher in women with hs-CRP ≥3 mg/L. After adjustment for age and time since menopause, the odds ratio for hs-CRP ≥3 mg/L was higher for sedentary lifestyle (4.7, 95% confidence interval [95%CI] 1.4-15.5) and carbohydrate intake (2.9, 95%CI 1.1-7.7). Conclusions sedentary lifestyle and high-carbohydrate intake were associated with low-grade chronic inflammation and cardiovascular risk in postmenopause. Thieme Publicações Ltda Rio de Janeiro, Brazil.

Genome-wide characterization of differentially expressed genes provides insights into regulatory network of heat stress response in radish (Raphanus sativus L.).

PubMed

Wang, Ronghua; Mei, Yi; Xu, Liang; Zhu, Xianwen; Wang, Yan; Guo, Jun; Liu, Liwang

2018-03-01

Heat stress (HS) causes detrimental effects on plant morphology, physiology, and biochemistry that lead to drastic reduction in plant biomass production and economic yield worldwide. To date, little is known about HS-responsive genes involved in thermotolerance mechanism in radish. In this study, a total of 6600 differentially expressed genes (DEGs) from the control and Heat24 cDNA libraries of radish were isolated by high-throughput sequencing. With Gene Ontology (GO) and Kyoto Encyclopedia of Genes and Genomes (KEGG) pathway analysis, some genes including MAPK, DREB, ERF, AP2, GST, Hsf, and Hsp were predominantly assigned in signal transductions, metabolic pathways, and biosynthesis and abiotic stress-responsive pathways. These pathways played significant roles in reducing stress-induced damages and enhancing heat tolerance in radish. Expression patterns of 24 candidate genes were validated by reverse-transcription quantitative PCR (RT-qPCR). Based mainly on the analysis of DEGs combining with the previous miRNAs analysis, the schematic model of HS-responsive regulatory network was proposed. To counter the effects of HS, a rapid response of the plasma membrane leads to the opening of specific calcium channels and cytoskeletal reorganization, after which HS-responsive genes are activated to repair damaged proteins and ultimately facilitate further enhancement of thermotolerance in radish. These results could provide fundamental insight into the regulatory network underlying heat tolerance in radish and facilitate further genetic manipulation of thermotolerance in root vegetable crops.

Characterization of Cardiopulmonary Exercise Testing Variables in Patients with Endomyocardial Fibrosis after Endocardial Resection

PubMed Central

Sayegh, Ana Luiza C.; dos Santos, Marcelo R.; de Oliveira, Patricia; Fernandes, Fábio; Rondon, Eduardo; de Souza, Francis R.; Salemi, Vera M. C.; Alves, Maria Janieire de N. N.; Mady, Charles

2017-01-01

Background Endomyocardial fibrosis (EMF) is a rare disease, characterized by diastolic dysfunction which leads to reduced peak oxygen consumption (VO2). Cardiopulmonary exercise testing (CPET) has been proved to be a fundamental tool to identify central and peripheral alterations. However, most studies prioritize peak VO2 as the main variable, leaving aside other important CPET variables that can specify the severity of the disease and guide the clinical treatment. Objective The aim of this study was to evaluate central and peripheral limitations in symptomatic patients with EMF by different CPET variables. Methods Twenty-six EMF patients (functional class III, NYHA) were compared with 15 healthy subjects (HS). Functional capacity was evaluated using CPET and diastolic and systolic functions were evaluated by echocardiography. Results Age and gender were similar between EMF patients and HS. Left ventricular ejection fraction was normal in EMF patients, but decreased compared to HS. Peak heart rate, peak workload, peak VO2, peak oxygen (O2) pulse and peak pulmonary ventilation (VE) were decreased in EMF compared to HS. Also, EMF patients showed increased Δ heart rate /Δ oxygen uptake and Δ oxygen uptake /Δ work rate compared to HS. Conclusion Determination of the aerobic capacity by noninvasive respiratory gas exchange during incremental exercise provides additional information about the exercise tolerance in patients with EMF. The analysis of different CPET variables is necessary to help us understand more about the central and peripheral alterations cause by both diastolic dysfunction and restrictive pattern. PMID:29364349

Functional Requirements for Heparan Sulfate Biosynthesis in Morphogenesis and Nervous System Development in C. elegans.

PubMed

Blanchette, Cassandra R; Thackeray, Andrea; Perrat, Paola N; Hekimi, Siegfried; Bénard, Claire Y

2017-01-01

The regulation of cell migration is essential to animal development and physiology. Heparan sulfate proteoglycans shape the interactions of morphogens and guidance cues with their respective receptors to elicit appropriate cellular responses. Heparan sulfate proteoglycans consist of a protein core with attached heparan sulfate glycosaminoglycan chains, which are synthesized by glycosyltransferases of the exostosin (EXT) family. Abnormal HS chain synthesis results in pleiotropic consequences, including abnormal development and tumor formation. In humans, mutations in either of the exostosin genes EXT1 and EXT2 lead to osteosarcomas or multiple exostoses. Complete loss of any of the exostosin glycosyltransferases in mouse, fish, flies and worms leads to drastic morphogenetic defects and embryonic lethality. Here we identify and study previously unavailable viable hypomorphic mutations in the two C. elegans exostosin glycosyltransferases genes, rib-1 and rib-2. These partial loss-of-function mutations lead to a severe reduction of HS levels and result in profound but specific developmental defects, including abnormal cell and axonal migrations. We find that the expression pattern of the HS copolymerase is dynamic during embryonic and larval morphogenesis, and is sustained throughout life in specific cell types, consistent with HSPGs playing both developmental and post-developmental roles. Cell-type specific expression of the HS copolymerase shows that HS elongation is required in both the migrating neuron and neighboring cells to coordinate migration guidance. Our findings provide insights into general principles underlying HSPG function in development.

How members of the human gut microbiota overcome the sulfation problem posed by glycosaminoglycans.

PubMed

Cartmell, Alan; Lowe, Elisabeth C; Baslé, Arnaud; Firbank, Susan J; Ndeh, Didier A; Murray, Heath; Terrapon, Nicolas; Lombard, Vincent; Henrissat, Bernard; Turnbull, Jeremy E; Czjzek, Mirjam; Gilbert, Harry J; Bolam, David N

2017-07-03

The human microbiota, which plays an important role in health and disease, uses complex carbohydrates as a major source of nutrients. Utilization hierarchy indicates that the host glycosaminoglycans heparin (Hep) and heparan sulfate (HS) are high-priority carbohydrates for Bacteroides thetaiotaomicron , a prominent member of the human microbiota. The sulfation patterns of these glycosaminoglycans are highly variable, which presents a significant enzymatic challenge to the polysaccharide lyases and sulfatases that mediate degradation. It is possible that the bacterium recruits lyases with highly plastic specificities and expresses a repertoire of enzymes that target substructures of the glycosaminoglycans with variable sulfation or that the glycans are desulfated before cleavage by the lyases. To distinguish between these mechanisms, the components of the B. thetaiotaomicron Hep/HS degrading apparatus were analyzed. The data showed that the bacterium expressed a single-surface endo-acting lyase that cleaved HS, reflecting its higher molecular weight compared with Hep. Both Hep and HS oligosaccharides imported into the periplasm were degraded by a repertoire of lyases, with each enzyme displaying specificity for substructures within these glycosaminoglycans that display a different degree of sulfation. Furthermore, the crystal structures of a key surface glycan binding protein, which is able to bind both Hep and HS, and periplasmic sulfatases reveal the major specificity determinants for these proteins. The locus described here is highly conserved within the human gut Bacteroides , indicating that the model developed is of generic relevance to this important microbial community.

Differential influence of hippocampal subfields to memory formation: insights from patients with temporal lobe epilepsy.

PubMed

Coras, Roland; Pauli, Elisabeth; Li, Jinmei; Schwarz, Michael; Rössler, Karl; Buchfelder, Michael; Hamer, Hajo; Stefan, Hermann; Blumcke, Ingmar

2014-07-01

To clarify the anatomical organization of human memory remains a major challenge in clinical neuroscience. Experimental data suggest dentate gyrus granule cells play a major role in memory acquisition, i.e. pattern separation and rapid pattern completion, whereas hippocampal CA1 neurons are implicated in place memory and autobiographical memory retrieval. Patients with temporal lobe epilepsy present with a broad spectrum of memory impairment, which can be assessed during clinical examination. Although long seizure histories may contribute to a pathophysiological reorganization of functional connectivity, surgical resection of the epileptic hippocampus offers a unique possibility to anatomically study the differential contribution of hippocampal subfields to compromised learning and memory in humans. Herein, we tested the hypothesis of hippocampal subfield specialization in a series of 100 consecutive patients with temporal lobe epilepsy submitted to epilepsy surgery. Memory profiles were obtained from intracarotid amobarbital testing and non-invasive verbal memory assessment before surgery, and correlated with histopathologically quantified cell loss pattern in hippocampal subfields obtained from the same patients using the new international consensus classification for hippocampal sclerosis proposed by the International League against Epilepsy (HS ILAE). Interestingly, patients with CA1 predominant cell loss (HS ILAE Type 2; n = 13) did not show declarative memory impairment and were indistinguishable from patients without any hippocampal cell loss (n = 19). In contrast, 63 patients with neuronal loss affecting all hippocampal subfields including CA1, CA4 and dentate gyrus (HS ILAE Type 1), or predominant cell loss in CA4 and partially affecting also CA3 and dentate gyrus (HS ILAE Type 3, n = 5) showed significantly reduced declarative memory capacities (intracarotid amobarbital testing: P < 0.001; verbal memory: P < 0.05). Our results suggested an alternative model of how memory processing can be organized amongst hippocampal subfields, and that CA1 pyramidal cells are less critically involved in declarative human memory acquisition compared to dentate gyrus granule cells or CA4/CA3 pyramidal cells. © The Author (2014). Published by Oxford University Press on behalf of the Guarantors of Brain. All rights reserved. For Permissions, please email: journals.permissions@oup.com.

Epidemiological Patterns of Ankle Sprains in Youth, High School, and College Football.

PubMed

Clifton, Daniel R; Koldenhoven, Rachel M; Hertel, Jay; Onate, James A; Dompier, Thomas P; Kerr, Zachary Y

2017-02-01

Variations in ankle injury rates and distributions among competition levels are unclear, but such data may help inform strategies to prevent ankle sprains during American football. To describe the epidemiological patterns of ankle sprains in youth, high school (HS), and collegiate American football. Descriptive epidemiological study. Data regarding youth, HS, and college football athletes were collected from 3 injury surveillance programs: (1) the Youth Football Safety Study (YFSS), (2) the National Athletic Treatment, Injury and Outcomes Network (NATION), and (3) the National Collegiate Athletic Association (NCAA) Injury Surveillance Program (ISP). During the 2012-2014 seasons, the YFSS, NATION, and NCAA ISP included 310, 184, and 71 football team-seasons, respectively. Athletic trainers (ATs) attended each practice and game and reported injuries and athlete-exposures (AEs) via their preferred injury documentation application. Ankle sprain rates for each type of ankle sprain were calculated overall, by event type (ie, practices and games), and specifically for severe injuries (ie, participation restriction time >21 days) and recurrent injuries (as defined by ATs). Rate ratios (RRs) were used to compare ankle sprain rates by competition level and event type. Injury proportion ratios (IPRs) were used to compare differences in severity, surgical needs, recurrence, injury mechanism, and injury activity by competition level. RRs and IPRs with 95% confidence intervals excluding 1.00 were considered statistically significant. A total of 124, 897, and 643 ankle sprains were reported in youth, HS, and college football, respectively. This led to respective rates of 0.59, 0.73, and 1.19 sprains per 1000 AEs. The ankle sprain rate in college football was higher than the rates in HS (RR = 1.64; 95% CI, 1.48-1.82) and youth (RR = 2.01; 95% CI, 1.65-2.43) football. The proportion of ankle sprains that were recurrent in youth football was higher than the proportions in HS (IPR = 2.73; 95% CI, 1.68-4.50) and college (IPR = 2.19; 95% CI, 1.33-3.61) football. Ankle sprain rates were highest in college athletes. However, level-specific variations in ankle sprain severity and recurrence may highlight the need to develop level-specific policies and prevention strategies to reduce injury incidence.

Abnormal gait pattern emerges during curved trajectories in high-functioning Parkinsonian patients walking in line at normal speed

PubMed Central

Godi, Marco; Giardini, Marica; Arcolin, Ilaria; Nardone, Antonio; Giordano, Andrea; Schieppati, Marco

2018-01-01

Background Several patients with Parkinson´s disease (PD) can walk normally along straight trajectories, and impairment in their stride length and cadence may not be easily discernible. Do obvious abnormalities occur in these high-functioning patients when more challenging trajectories are travelled, such as circular paths, which normally implicate a graded modulation in the duration of the interlimb gait cycle phases? Methods We compared a cohort of well-treated mildly to moderately affected PD patients to a group of age-matched healthy subjects (HS), by deliberately including HS spontaneously walking at the same speed of the patients with PD. All participants performed, in random order: linear and circular walking (clockwise and counter-clockwise) at self-selected speed. By means of pressure-sensitive insoles, we recorded walking speed, cadence, duration of single support, double support, swing phase, and stride time. Stride length-cadence relationships were built for linear and curved walking. Stride-to-stride variability of temporal gait parameters was also estimated. Results Walking speed, cadence or stride length were not different between PD and HS during linear walking. Speed, cadence and stride length diminished during curved walking in both groups, stride length more in PD than HS. In PD compared to HS, the stride length-cadence relationship was altered during curved walking. Duration of the double-support phase was also increased during curved walking, as was variability of the single support, swing phase and double support phase. Conclusion The spatio-temporal gait pattern and variability are significantly modified in well-treated, high-functioning patients with PD walking along circular trajectories, even when they exhibit no changes in speed in straight-line walking. The increased variability of the gait phases during curved walking is an identifying characteristic of PD. We discuss our findings in term of interplay between control of balance and of locomotor progression: the former is challenged by curved trajectories even in high-functioning patients, while the latter may not be critically affected. PMID:29750815

Effects of Co doping on the metamagnetic states of the ferromagnetic fcc Fe-Co alloy.

PubMed

Ortiz-Chi, Filiberto; Aguayo, Aarón; de Coss, Romeo

2013-01-16

The evolution of the metamagnetic states in the ferromagnetic face centered cubic (fcc) Fe(1-x)Co(x) alloy as a function of Co concentration has been studied by means of first-principles calculations. The ground state properties were obtained using the full-potential linear augmented plane wave method and the generalized gradient approximation for the exchange-correlation functional. The alloying was modeled using the virtual crystal approximation and the magnetic states were obtained from the calculations of the total energy as a function of the spin moment, using the fixed spin moment method. For ferromagnetic fcc Fe, the binding-energy curve shows metamagnetic behavior, with two minima corresponding to a small-volume, low-spin (LS) state and a large-volume, high-spin (HS) state, which are separated by a small energy (E(LS) ≲ E(HS)). The evolution of the magnetic moment, the exchange integral (J), and the binding-energy curve is analyzed in the whole range of Co concentrations (x). The magnetic moment corresponding to the HS state decreases monotonically from 2.6 μ(B)/atom in fcc Fe to 1.7 μ(B)/atom in fcc Co. In contrast, the exchange integral for the HS state shows a maximum at around x = 0.45. The thermal dependence of the lattice parameter is evaluated with a method based on statistical mechanics using the binding-energy curve as an effective potential. It is observed that the behavior of the lattice parameter with temperature is tuned by Co doping, from negative thermal expansion in fcc Fe to positive thermal expansion in fcc Co, through the modification of the energetics of the metamagnetic states.

Boils at Frictional Locations in a Patient with Hidradenitis Suppurativa.

PubMed

Boer, Jurr; Mihajlovic, Dalibor

2016-12-01

Dear Editor, Hidradenitis suppurativa (HS) is a chronic, recurrent, inflammatory skin disease. The primary clinical presentation are painful inflamed nodules or boils of inverse areas, i.e. the axillary and anogenito-crural regions, but it can also involve the infra- and inter-mammary regions (1,2). The etiology of HS is not clearly defined. Obesity, smoking, and genetic factors are considered important risk factors. In addition, it has also been suggested that friction may contribute to the development of HS, especially in the obese, but this is based on highly anecdotal reports (3-5). We describe a case with classic HS, obesity, and HS-like lesions at the position of the bra strap, suggesting that mechanical stress was an external pathogenic factor for HS development. A 33-year old woman presented with an 18-year history of chronic, recurrent, inflammatory nodules in the axillae, the groin, the pubic region, and to a lesser extent the abdomen and buttocks. She was obese with as result of 33.2 kg/m-2 of 33.2, had a positive family history of two first grade family members with HS, and was a smoker (19 Pack years). There were no other known comorbidities. The inflamed lesions had been treated with several courses of oral antibiotics (minocycline, erythromycin, and combination therapy of clindamycin and rifampicine) and surgical treatments: lancing, deroofing, and excisions (2,6). On examination, there were nodules, folliculitis, cysts, and depressed scars in the axillae and groins, including the inner thighs (Figure 1). On the chest, corresponding to where the lower edge of the patient's bra was usually located, a superficial nodule and follicular papules were observed, exactly coinciding with the red stripe caused by mechanical stress (friction and pressure) of the bra edge. There was no skin fold present on the location of the HS lesions, and there were no lesions observed in the intermammary region or on the side of the breasts in contact with the skin of the thorax (skin to skin contact) (Figure 2). Cultures from skin swabs showed commensal skin flora and moderate mixed anaerobic bacteria, as would be expected in a HS lesion. It is well documented that HS is a disease of the obese. However, the role of friction as an environmental factor is poorly documented. Patients report that environmental factors such as tight-fitting clothing or friction could cause flares in the disease (2). Furthermore, it has been postulated that friction may contribute to the development of HS by stimulating interfollicular hyperplasia (7). HS lesions arranged in a linear pattern suggest an environmental influence and suggests an etiopathogenic role for mechanical stress. Waistline, or as in this case the chest line, distribution indicates that wearing of tight waistbands, wide belts, or bras may induce HS in predisposed individuals. To our knowledge, there is only one case report describing an obese patient with classic HS (typical lesions in predilection areas) who developed HS like lesions on the upper abdomen (waist) at the height of the waistband as well as under the lower abdominal apron (skin on skin contact) (8). Two other reports suggesting a pathogenic role for mechanical stress are flawed, however, as neither of the cases showed signs of concomitant classic HS or had a family history, bringing into question the implied association of HS (9,10). In summary, we presented a case with classic HS locations (typical lesions on typical locations, i.e. the axillae and inguino-crural regions) developing inflammatory lesions on the chest at the location closely corresponding to where the bra strap was exerting mechanical pressure and friction on the skin. The lesions were clinically and microbiologically compatible with ectopic HS lesions. The chest is an atypical HS location free of apocrine sweat glands. It is postulated that these lesions may have been induced by mechanical stress, additionally triggered by the pro-inflammatory state of the obese body. Patients are encouraged to avoid friction from environmental factors such as tight clothing.

Synthesis, physicochemical characterization and biological evaluation of chitosan sulfate as heparan sulfate mimics.

PubMed

Doncel-Pérez, Ernesto; Aranaz, Inmaculada; Bastida, Agatha; Revuelta, Julia; Camacho, Celia; Acosta, Niuris; Garrido, Leoncio; Civera, Concepción; García-Junceda, Eduardo; Heras, Angeles; Fernández-Mayoralas, Alfonso

2018-07-01

Despite the relevant biological functions of heparan sulfate (HS) glycosaminoglycans, their limited availability and the chemical heterogeneity from natural sources hamper their use for biomedical applications. Chitosan sulfates (ChS) exhibit structural similarity to HSs and may mimic their biological functions. We prepared a variety of ChS with different degree of sulfation to evaluate their ability to mimic HS in protein binding and to promote neural cell division and differentiation. The structure of the products was characterized using various spectroscopic and analytical methods. The study of their interaction with different growth factors showed that ChS bound to the proteins similarly or even better than heparin. In cell cultures, a transition effect on cell number was observed as a function of ChS concentration. Differences in promoting the expression of the differentiation markers were also found depending on the degree of sulfation and modification in the chitosan. Copyright © 2018 Elsevier Ltd. All rights reserved.

Patterns of Late Quaternary hydrologic variability and atmospheric change inferred from a Northern California speleothem

NASA Astrophysics Data System (ADS)

Oster, J. L.; Weisman, I. E.; Sharp, W. D.; Ibarra, D. E.

2017-12-01

The synthesis of hydrologically sensitive proxy records across western North America reveals spatial patterns of variability that persist, with some variation, over multiple temporal scales. For example, tree ring records from the last century highlight a distinct north-south dipole pattern in the response of regional precipitation anomalies to ENSO and the PDO, while a similar dipole pattern of wet and dry precipitation anomalies developed across the region in response to climate forcing at the Last Glacial Maximum (LGM). Hydrologically sensitive proxy records from the intervening transition zone can shed light on the stationarity and spatial scale of this pattern over time. Here we present records of δ18O and δ13C from a Lake Shasta Caverns stalagmite (LSC3) from Northern California that grew from 36 to 14 ka. This cave, located at 40.8°N, is situated within the transition zone and is well-positioned to enhance our understanding of regional precipitation patterns and moisture transport variability during the last glacial period and deglaciation. Six years of weekly rain isotope data indicate that varying atmospheric temperatures and moisture sources are primary controls on δ18O in Northern California precipitation. Increased δ18O and δ13C in LSC3 and slower stalagmite growth rates during MIS 2 suggest increased subtropical moisture but also dry conditions in Northern California. The δ13C record displays distinct millennial-scale oscillations during MIS 3, suggesting drier conditions also occurred during interstadials associated with Dansgaard-Oeschger cycles. The LSC3 δ18O record documents changes synchronous with δ18O in the Fort Stanton stalagmite in New Mexico, though sometimes in phase (e.g. during Heinrich Stadial 1; HS1) and sometimes anti-phased (e.g. during the Bölling-Alleröd). Likewise, the LSC3 δ13C record suggests a transition from wet to drier conditions during HS1 in marked contrast to many more southerly records that indicate wetter conditions later in HS1. These comparisons show that changes in Northern California climate were both in and out of phase with hydroclimate variations occurring to the south and southeast. Thus, the LSC3 record refines our understanding of spatial patterns of hydroclimatic change in western North America.

pPKCδ activates SC35 splicing factor during H9c2 myoblastic differentiation.

PubMed

Zara, Susi; Falconi, Mirella; Rapino, Monica; Zago, Michela; Orsini, Giovanna; Mazzotti, Giovanni; Cataldi, Amelia; Teti, Gabriella

2011-01-01

Although Protein Kinase C (PKC) isoforms' role in the neonatal and adult cardiac tissue development and ageing has been widely described "in vivo", the interaction of such enzymes with specific nuclear substrates needs to be investigated. The aim of our research has been the study of the expression, localization and interaction with the splicing factor SC35 of PKC isoforms (α, δ, ε, ζ) and their potential role in modulating the transcription machinery. H9c2 cells induced to myoblast differentiation in the presence of 1% Horse Serum (HS) have represented our experimental model. The expression of PKC isoforms, their distribution and interaction with SC35 have been evaluated by western blotting, co-immunoprecipitation and double gold immunolabeling for transmission and scanning electron microscopy. Our results show PKCδ as the most expressed isoform in differentiated cells. Surprisingly, the distribution of PKCδ and SC35 does not show any significant modification between 10%FBS and 1%HS treated samples and no co-localization is observed. Moreover the interaction between the phosphorylated form of PKCδ (pPKCδ) and SC35 increases, is distributed and co-localizes within the nucleus of differentiated H9c2. These data represent reasonable evidence of pPKCδ mediated SC35 splicing factor activation, suggesting its direct effect on transcription via interaction with the transcription machinery. Furthermore, this co-localization represents a crucial event resulting in downstream changes in transcription of components which determine the morphological modifications related to cardiomyoblast differentiated phenotype.

Separation of sulfated urinary glycosaminoglycans by high-resolution electrophoresis for isotyping of mucopolysaccharidoses in Malaysia.

PubMed

Nor, Azimah; Zabedah, Md Yunus; Norsiah, Md Desa; Ngu, Lock Hock; Suhaila, Abd Rahman

2010-06-01

Mucopolysaccharidoses (MPS) are a group of inherited disorders caused by the deficiency of specific lysosomal enzymes involved in glycosaminoglycans (GAGs) degradation. Currently, there are 11 enzyme deficiencies resulting in seven distinct MPS clinical syndromes and their subtypes. Different MPS syndromes cannot be clearly distinguished clinically due to overlapping signs and symptoms. Measurement of GAGs content in urine and separation of GAGs using high-resolution electrophoresis (HRE) are very useful initial screening tests for isotyping of MPS before specific enzyme diagnostics. In this study, we measured total urinary GAGs by a method using dimethylmethylene blue (DMB), and followed by isolation and separation of GAGs using high resolution electrophoresis (HRE) technique. Of 760 urine samples analyzed, 40 have abnormal GAGs HRE patterns. Thirty-five of these 40 cases have elevated urinary GAGs levels as well. These abnormal HRE patterns could be classified into 4 patterns: Pattern A (elevated DS and HS; suggestive of MPS I, II or VII; 16 cases), Pattern B (elevated HS and CS; suggestive of MPS III; 17 cases), and Pattern C (elevated KS and CS; suggestive of MPS IV, 5 cases), and Pattern D (elevated DS; suggestive of MPS VI; 2 cases). Based on the GAGs HRE pattern and a few discriminating clinical signs, we performed selective enzymatic investigation in 16 cases. In all except one case with MPS VII, the enzymatic diagnosis correlated well with the provisional MPS type as suggested by the abnormal HRE pattern. Our results showed that GAGs HRE is a useful, inexpensive and practical first-line screening test when MPS is suspected clinically, and it provides an important guide to further enzymatic studies on a selective basis.

Tropical Hydroclimate Change during Heinrich Stadial 1: An Integrative Proxy-Model Synthesis

NASA Astrophysics Data System (ADS)

Lawman, A. E.; Sun, T.; Shanahan, T. M.; Di Nezio, P. N.; Gomez, K.; Piatrunia, N.; Sun, C.; Wu, X.; Kageyama, M.; Merkel, U.; Otto-Bliesner, B. L.; Abe-Ouchi, A.; Lohmann, G.; Singarayer, J. S.

2017-12-01

We explore the response of tropical climate to abrupt cooling of the North Atlantic (NA) during Heinrich Stadial 1 (HS1) combining paleoclimate proxies with model simulations. A total of 146 published paleoclimate records from tropical locations are used to categorize whether HS1 was wetter, drier, or unchanged relative to a deglacial baseline state. Only records with sufficient resolution to resolve HS1 and sufficient length to characterize the deglacial trend are considered. This synthesis reveals large-scale patterns of hydroclimate change relative to glacial conditions, confirming previously reported weaker Indian summer monsoon, a wetter southern Africa, and drying over the Caribbean. Our synthesis also reveals large-scale drying over the Maritime continent as well as wetter conditions in northern Australia and southern tropical South America. Our reinterpretation of the available proxy data reveals far more complexity and uncertainties for equatorial East Africa, a region that appears to straddle a pattern of dryer conditions to the north and wetter conditions to the south. Overall, these patterns of hydroclimate change depart from a southward shift of the Inter Tropical Convergence Zone (ITCZ), particularly outside the tropical Atlantic. We explore mechanisms driving these changes using a multi-model ensemble of "hosing" simulations performed relative to glacial conditions. The models show robust weakening of the Afro-Asian Monsoon, which we attribute to ventilation of colder mid-latitude air. Not all models simulate the remaining patterns inferred from the proxy data. The best-agreeing models indicate that cooling over the tropical NA and the Caribbean may be essential to communicate the response to the global tropics. This response can induce warming over the tropical South Atlantic via the wind-evaporation-SST feedback, driving wetter conditions in South Africa and tropical South America. Cooling over the Caribbean is communicated to the Pacific over the Central American isthmus resulting in an El Niño-like pattern accompanied by drying over the Maritime Continent - as seen in the proxy data. Together these results show a dominant role for altered tropical SST gradients driving changes in tropical rainfall, and a lesser role for inter-hemispheric shifts in the ITCZ.

ANTIDIABETIC AND ANTIDYSLIPIDEMIC EFFECTS OF HELIOTROPIUM STRIGOSUM IN RAT MODELS OF TYPE I AND TYPE II DIABETES.

PubMed

Chaudhry, Shafqat Rasul; Akram, Adnan; Aslam, Naveed; Asif, Muhammad; Wajid, Muhammad; Kinfe, Thomas; Jabeen, Qaiser; Muhammad, Sajjad

2016-11-01

Heliotropiumz stnigosum Wilid. (Boraginaceae) is used traditionally as a laxative, diuretic, and as a treatment for snake bites and stings of nettles. Recent investigations have shown anti-inflammatory and antioxidant activity of H. sorigosum. However, antihyperglycemic and antidyslipidemic activity of H. strigosum has not been investigated to date and we aimed to explore these activities of the crude aqueous methanolic extract of thEaerial parts of H. strigosum (Hs.Cr). Hs.Cr was administered orally at doses of 100, 300, and 500 mg/kg in alloxan-induced diabetic rats (type I diabetes) and fructose-fed rats (type II diabetes). The fasting blood glucose (FBG) concentration was assessed by glucometer, while semum total cholesterol, triglycerides and HDL were estimated by using standard kits. The FBG concentration significantly (p < 0.05) decreased in dose-dependent pattern in both alloxan-induced diabetic and fructose-fed rats on Hs.Cr administration. The percentage glucose reductions in alloxanized rats with glibenclamide, Hs.Cr 100, 300, and 500 mg/kg were obeserved to be 67, 36, 56 and 62%, respectively. In fructose-fed rats, the percentage glucose redutions associated with metformin, Hs.Cr 100, 300, and 500 mg/kg were 23, 5, 11 and 12%, respectively. The extract also corrected the dyslipidemia associated with fructose and alloxan-induced diabetes by significantly (p < 0.00 1) decreasing the concentration of serum total cholesterol, triglycerides and LDL and by increasing HDL concentration. Our data demonstrate that the H. stigosum has antidiabetic and antidyslipidemic effects, thus encouraging further studies.

A combined high-sugar and high-saturated-fat dietary pattern is associated with more depressive symptoms in a multi-ethnic population: the HELIUS (Healthy Life in an Urban Setting) study.

PubMed

Vermeulen, Esther; Stronks, Karien; Snijder, Marieke B; Schene, Aart H; Lok, Anja; de Vries, Jeanne H; Visser, Marjolein; Brouwer, Ingeborg A; Nicolaou, Mary

2017-09-01

To identify a high-sugar (HS) dietary pattern, a high-saturated-fat (HF) dietary pattern and a combined high-sugar and high-saturated-fat (HSHF) dietary pattern and to explore if these dietary patterns are associated with depressive symptoms. We used data from the HELIUS (Healthy Life in an Urban Setting) study and included 4969 individuals aged 18-70 years. Diet was assessed using four ethnic-specific FFQ. Dietary patterns were derived using reduced rank regression with mono- and disaccharides, saturated fat and total fat as response variables. The nine-item Patient Health Questionnaire (PHQ-9) was used to assess depressive symptoms by using continuous scores and depressed mood (identified using the cut-off point: PHQ-9 sum score ≥10). The Netherlands. Three dietary patterns were identified; an HSHF dietary pattern (including chocolates, red meat, added sugars, high-fat dairy products, fried foods, creamy sauces), an HS dietary pattern (including sugar-sweetened beverages, added sugars, fruit (juices)) and an HF dietary pattern (including high-fat dairy products, butter). When comparing extreme quartiles, consumption of an HSHF dietary pattern was associated with more depressive symptoms (Q1 v. Q4: β=0·18, 95 % CI 0·07, 0·30, P=0·001) and with higher odds of depressed mood (Q1 v. Q4: OR=2·36, 95 % CI 1·19, 4·66, P=0·014). No associations were found between consumption of the remaining dietary patterns and depressive symptoms. Higher consumption of an HSHF dietary pattern is associated with more depressive symptoms and with depressed mood. Our findings reinforce the idea that the focus should be on dietary patterns that are high in both sugar and saturated fat.

Modal Parameters Evaluation in a Full-Scale Aircraft Demonstrator under Different Environmental Conditions Using HS 3D-DIC.

PubMed

Molina-Viedma, Ángel Jesús; López-Alba, Elías; Felipe-Sesé, Luis; Díaz, Francisco A; Rodríguez-Ahlquist, Javier; Iglesias-Vallejo, Manuel

2018-02-02

In real aircraft structures the comfort and the occupational performance of crewmembers and passengers are affected by the presence of noise. In this sense, special attention is focused on mechanical and material design for isolation and vibration control. Experimental characterization and, in particular, experimental modal analysis, provides information for adequate cabin noise control. Traditional sensors employed in the aircraft industry for this purpose are invasive and provide a low spatial resolution. This paper presents a methodology for experimental modal characterization of a front fuselage full-scale demonstrator using high-speed 3D digital image correlation, which is non-invasive, ensuring that the structural response is unperturbed by the instrumentation mass. Specifically, full-field measurements on the passenger window area were conducted when the structure was excited using an electrodynamic shaker. The spectral analysis of the measured time-domain displacements made it possible to identify natural frequencies and full-field operational deflection shapes. Changes in the modal parameters due to cabin pressurization and the behavior of different local structural modifications were assessed using this methodology. The proposed full-field methodology allowed the characterization of relevant dynamic response patterns, complementing the capabilities provided by accelerometers.

Modal Parameters Evaluation in a Full-Scale Aircraft Demonstrator under Different Environmental Conditions Using HS 3D-DIC

PubMed Central

López-Alba, Elías; Felipe-Sesé, Luis; Díaz, Francisco A.; Rodríguez-Ahlquist, Javier; Iglesias-Vallejo, Manuel

2018-01-01

In real aircraft structures the comfort and the occupational performance of crewmembers and passengers are affected by the presence of noise. In this sense, special attention is focused on mechanical and material design for isolation and vibration control. Experimental characterization and, in particular, experimental modal analysis, provides information for adequate cabin noise control. Traditional sensors employed in the aircraft industry for this purpose are invasive and provide a low spatial resolution. This paper presents a methodology for experimental modal characterization of a front fuselage full-scale demonstrator using high-speed 3D digital image correlation, which is non-invasive, ensuring that the structural response is unperturbed by the instrumentation mass. Specifically, full-field measurements on the passenger window area were conducted when the structure was excited using an electrodynamic shaker. The spectral analysis of the measured time-domain displacements made it possible to identify natural frequencies and full-field operational deflection shapes. Changes in the modal parameters due to cabin pressurization and the behavior of different local structural modifications were assessed using this methodology. The proposed full-field methodology allowed the characterization of relevant dynamic response patterns, complementing the capabilities provided by accelerometers. PMID:29393897

Genome-wide analyses of four major histone modifications in Arabidopsis hybrids at the germinating seed stage.

PubMed

Zhu, Anyu; Greaves, Ian K; Dennis, Elizabeth S; Peacock, W James

2017-02-07

Hybrid vigour (heterosis) has been used for decades in cropping agriculture, especially in the production of maize and rice, because hybrid varieties exceed their parents in plant biomass and seed yield. The molecular basis of hybrid vigour is not fully understood. Previous studies have suggested that epigenetic systems could play a role in heterosis. In this project, we investigated genome-wide patterns of four histone modifications in Arabidopsis hybrids in germinating seeds. We found that although hybrids have similar histone modification patterns to the parents in most regions of the genome, they have altered patterns at specific loci. A small subset of genes show changes in histone modifications in the hybrids that correlate with changes in gene expression. Our results also show that genome-wide patterns of histone modifications in geminating seeds parallel those at later developmental stages of seedlings. Ler/C24 hybrids showed similar genome-wide patterns of histone modifications as the parents at an early germination stage. However, a small subset of genes, such as FLC, showed correlated changes in histone modification and in gene expression in the hybrids. The altered patterns of histone modifications for those genes in hybrids could be related to some heterotic traits in Arabidopsis, such as flowering time, and could play a role in hybrid vigour establishment.

The effect of cyclical and severe heat stress on growth performance and metabolism in Afshari lambs.

PubMed

Mahjoubi, E; Yazdi, M Hossein; Aghaziarati, N; Noori, G R; Afsarian, O; Baumgard, L H

2015-04-01

The extent to which reduced feed intake contributes to decreased growth during heat stress (HS) in the ovine model is not clear. To evaluate the impact of decreased DMI on performance, we conducted an experiment on growing lambs experiencing a cyclical but extensive heat load. Sixteen intact male Afshari lambs (40.1 ± 1.9 kg) were used in a completely randomized design in 2 periods. In period 1, all 16 lambs were housed in thermal neutral (TN) conditions (22.2 ± 3.1°C and a temperature-humidity index [THI] of 67.9 ± 3.2) and fed at libitum for 8 d. In period 2 (P2), which lasted 9 d, 8 lambs were subjected to a cyclical HS condition (33.0 to 45.0°C and a THI of more than 80 at least for 24 h/d and more than 90 for 8 h/d). The other 8 lambs were maintained in TN conditions but pair-fed (pair-fed thermal neutral [PFTN]) to the HS lambs. During each period, DMI and water intake were measured daily. Respiration rate, rectal temperature, and skin temperature at the shoulder, rump, and front and rear leg were recorded at 0700 and 1400 h daily. Dry matte intake declined (17.5%; P < 0.01) in HS lambs and, by design, the temporal pattern and magnitude of reduced feed intake was similar in the PFTN controls. Water intake increased (19%; P < 0.05) during P2 in HS but not in the PFTN controls. Heat stress increased the 0700 and 1400 h skin temperature at the shoulder (5 and 9.2%), rump (6.2 and 10.3%), rear (6 and 9.2%), and front leg (6.5 and 9.8%) and respiratory rates (84 and 163% [P < 0.01]at 0700 and 1400 h, respectfully), but only the 1400 h rectal temperature was increased (P < 0.01; 0.65°C) in HS lambs. Neither environment nor period affected blood urea nitrogen and glucose concentrations. However, circulating NEFA and insulin were increased and declined (P < 0.01) in PFTN lambs, respectively, but neither variable was altered in the HS lambs. Growth was reduced in P2 for lambs in both treatments, but despite being on a similar reduced plane of nutrition, the HS lambs' ADG was more than 2-fold greater than the PFTN controls. These results indicate that HS markedly alters the energetics of weight gain during growth and that the effects of HS are dependent on the severity of the heat load.

Paleolithic and Mediterranean Diet Pattern Scores Are Inversely Associated with Biomarkers of Inflammation and Oxidative Balance in Adults.

PubMed

Whalen, Kristine A; McCullough, Marjorie L; Flanders, W Dana; Hartman, Terryl J; Judd, Suzanne; Bostick, Roberd M

2016-06-01

Chronic inflammation and oxidative balance are associated with poor diet quality and risk of cancer and other chronic diseases. A diet-inflammation/oxidative balance association may relate to evolutionary discordance. We investigated associations between 2 diet pattern scores, the Paleolithic and the Mediterranean, and circulating concentrations of 2 related biomarkers, high-sensitivity C-reactive protein (hsCRP), an acute inflammatory protein, and F2-isoprostane, a reliable marker of in vivo lipid peroxidation. In a pooled cross-sectional study of 30- to 74-y-old men and women in an elective outpatient colonoscopy population (n = 646), we created diet scores from responses on Willett food-frequency questionnaires and measured plasma hsCRP and F2-isoprostane concentrations by ELISA and gas chromatography-mass spectrometry, respectively. Both diet scores were calculated and categorized into quintiles, and their associations with biomarker concentrations were estimated with the use of general linear models to calculate and compare adjusted geometric means, and via unconditional ordinal logistic regression. There were statistically significant trends for decreasing geometric mean plasma hsCRP and F2-isoprostane concentrations with increasing quintiles of the Paleolithic and Mediterranean diet scores. The multivariable-adjusted ORs comparing those in the highest with those in the lowest quintiles of the Paleolithic and Mediterranean diet scores were 0.61 (95% CI: 0.36, 1.05; P-trend = 0.06) and 0.71 (95% CI: 0.42, 1.20; P-trend = 0.01), respectively, for a higher hsCRP concentration, and 0.51 (95% CI: 0.27, 0.95; P-trend 0.01) and 0.39 (95% CI: 0.21, 0.73; P-trend = 0.01), respectively, for a higher F2-isoprostane concentration. These findings suggest that diets that are more Paleolithic- or Mediterranean-like may be associated with lower levels of systemic inflammation and oxidative stress in humans. © 2016 American Society for Nutrition.

Paleolithic and Mediterranean Diet Pattern Scores Are Inversely Associated with Biomarkers of Inflammation and Oxidative Balance in Adults123

PubMed Central

McCullough, Marjorie L; Flanders, W Dana; Hartman, Terryl J; Judd, Suzanne; Bostick, Roberd M

2016-01-01

Background: Chronic inflammation and oxidative balance are associated with poor diet quality and risk of cancer and other chronic diseases. A diet–inflammation/oxidative balance association may relate to evolutionary discordance. Objective: We investigated associations between 2 diet pattern scores, the Paleolithic and the Mediterranean, and circulating concentrations of 2 related biomarkers, high-sensitivity C-reactive protein (hsCRP), an acute inflammatory protein, and F2-isoprostane, a reliable marker of in vivo lipid peroxidation. Methods: In a pooled cross-sectional study of 30- to 74-y-old men and women in an elective outpatient colonoscopy population (n = 646), we created diet scores from responses on Willett food-frequency questionnaires and measured plasma hsCRP and F2-isoprostane concentrations by ELISA and gas chromatography–mass spectrometry, respectively. Both diet scores were calculated and categorized into quintiles, and their associations with biomarker concentrations were estimated with the use of general linear models to calculate and compare adjusted geometric means, and via unconditional ordinal logistic regression. Results: There were statistically significant trends for decreasing geometric mean plasma hsCRP and F2-isoprostane concentrations with increasing quintiles of the Paleolithic and Mediterranean diet scores. The multivariable-adjusted ORs comparing those in the highest with those in the lowest quintiles of the Paleolithic and Mediterranean diet scores were 0.61 (95% CI: 0.36, 1.05; P-trend = 0.06) and 0.71 (95% CI: 0.42, 1.20; P-trend = 0.01), respectively, for a higher hsCRP concentration, and 0.51 (95% CI: 0.27, 0.95; P-trend 0.01) and 0.39 (95% CI: 0.21, 0.73; P-trend = 0.01), respectively, for a higher F2-isoprostane concentration. Conclusion: These findings suggest that diets that are more Paleolithic- or Mediterranean-like may be associated with lower levels of systemic inflammation and oxidative stress in humans. PMID:27099230

Marijuana and driver behaviors : historic and social observations among fatal accident operators and a control sample

DOT National Transportation Integrated Search

1976-05-01

The final report, Part III for DOT HS-310-3-595 is an analysis and evaluation of the data from 1068 motor vehicle operators in the greater Boston area with a focal interest in marijuana use patterns and corresponding demographic, psychosocial, alcoho...

A role for heparan sulfate 3-O-sulfotransferase isoform 2 in herpes simplex virus type 1 entry and spread

DOE Office of Scientific and Technical Information (OSTI.GOV)

O'Donnell, Christopher D.; Department of Ophthalmology and Visual Sciences, College of Medicine, University of Illinois at Chicago, Chicago, IL 60612; Tiwari, Vaibhav

2006-03-15

Heparan sulfate (HS) 3-O-sulfotransferase isoform-2 (3-OST-2), which belongs to a family of enzymes capable of generating herpes simplex virus type-1 (HSV-1) entry and spread receptors, is predominantly expressed in human brain. Despite its unique expression pattern, the ability of 3-OST-2 to mediate HSV-1 entry and cell-to-cell fusion is not known. Our results demonstrate that expression of 3-OST-2 can render Chinese hamster ovary K1 (CHO-K1) cells susceptible to entry of wild-type and mutant strains of HSV-1. Evidence for generation of gD receptors by 3-OST-2 were suggested by gD-mediated interference assay and the ability of 3-OST-2-expressing CHO-K1 cells to preferentially bind HSV-1more » gD, which could be reversed by prior treatment of cells with HS lyases (heparinases II/III). In addition, 3-OST-2-expressing CHO-K1 cells acquired the ability to fuse with cells-expressing HSV-1 glycoproteins, a phenomenon that mimics a way of viral spread in vivo. Demonstrating specificity, the cell fusion was inhibited by soluble 3-O-sulfated forms of HS, but not unmodified HS. Taken together, our results raise the possibility of a role of 3-OST-2 in the spread of HSV-1 infection in the brain.« less

A neutron diffraction study of the magnetic phases of CsCuCl3 for in-plane fields up to 17 T

NASA Astrophysics Data System (ADS)

Stüßer, N.; Schotte, U.; Hoser, A.; Meschke, M.; Meißner, M.; Wosnitza, J.

2002-05-01

Neutron diffraction investigations have been performed to study the magnetization process of CsCuCl3 with the magnetic field aligned within the ab-plane. In zero field the stacked, triangular-lattice antiferromagnet (TLA) CsCuCl3 has a helical structure incommensurate in the chain direction normal to the ab-plane. The magnetic phase diagram was investigated from 2 K up to TN in fields up to 17 T. The phase line for the expected incommensurate-commensurate (IC-C) phase transition could be determined throughout the whole phase diagram. At low temperature the IC-C transition is roughly at half the saturation field HS. The neutron diffraction patterns were found to be well described by a sinusoidally modulated spiral in fields up to HS/3. The initial increase of the scattering intensity in rising field indicates a continuous reduction of the spin frustration on the triangular lattice. Between HS/3 and HS/2 a new phase occurs where the spiral vector has a plateau in its field dependence. Close to the IC-C transition a growing asymmetry of magnetic satellite-peak intensities indicates domain effects which are related to the lifting of the chiral degeneracy in the ab-plane in rising field. The phase diagram obtained has some similarities with those calculated for stacked TLAs by considering the effects of quantum and thermal fluctuations.

High invertase activity in tomato reproductive organs correlates with enhanced sucrose import into, and heat tolerance of, young fruit

PubMed Central

Li, Zhimiao; Palmer, William M.; Martin, Antony P.; Wang, Rongqing; Rainsford, Frederick; Jin, Ye; Patrick, John W.; Yang, Yuejian; Ruan, Yong-Ling

2012-01-01

Heat stress can cause severe crop yield losses by impairing reproductive development. However, the underlying mechanisms are poorly understood. We examined patterns of carbon allocation and activities of sucrose cleavage enzymes in heat-tolerant (HT) and -sensitive (HS) tomato (Solanum lycopersicum L.) lines subjected to normal (control) and heat stress temperatures. At the control temperature of 25/20 °C (day/night) the HT line exhibited higher cell wall invertase (CWIN) activity in flowers and young fruits and partitioned more sucrose to fruits but less to vegetative tissues as compared to the HS line, independent of leaf photosynthetic capacity. Upon 2-, 4-, or 24-h exposure to day or night temperatures of 5 °C or more above 25/20 °C, cell wall (CWIN) and vacuolar invertases (VIN), but not sucrose synthase (SuSy), activities in young fruit of the HT line were significantly higher than those of the HS line. The HT line had a higher level of transcript of a CWIN gene, Lin7, in 5-day fruit than the HS line under control and heat stress temperatures. Interestingly, heat induced transcription of an invertase inhibitor gene, INVINH1, but reduced its protein abundance. Transcript levels of LePLDa1, encoding phospholipase D, which degrades cell membranes, was less in the HT line than in the HS line after exposure to heat stress. The data indicate that high invertase activity of, and increased sucrose import into, young tomato fruit could contribute to their heat tolerance through increasing sink strength and sugar signalling activities, possibly regulating a programmed cell death pathway. PMID:22105847

Sex differences in the impact of the Mediterranean diet on systemic inflammation.

PubMed

Bédard, Alexandra; Lamarche, Benoît; Corneau, Louise; Dodin, Sylvie; Lemieux, Simone

2015-05-12

Some intervention trials have reported a reduction in systemic inflammation with the Mediterranean diet (MedDiet) while others have observed no effect. Despite the fact that sex differences have been highlighted in the inflammatory regulation, it is still not known whether MedDiet exerts similar effects on systemic inflammation in men and women. The aim of this study was therefore to investigate sex differences in the effects of the MedDiet on high-sensitivity C-reactive protein (hs-CRP). Participants were 35 men and 27 premenopausal women (24-53 years) presenting a slightly deteriorated lipid profile. All foods were provided to participants during a 4-week isocaloric MedDiet. At baseline, women had higher hs-CRP concentrations than men (P = 0.03). No sex difference was observed in hs-CRP response to the MedDiet (P for sex-by-time interaction = 0.36), with both men and women experiencing no change (respectively P = 0.62 and P > 0.99). When subgroups were formed according to hs-CRP concentration before the MedDiet phase, men with elevated baseline values (≥2 mg/l) experienced a reduction in hs-CRP over time with the MedDiet (-26.5 %) while an increase was observed in men with lower baseline values (+96.6 %; P for group-by-time interaction = 0.02). This pattern of change was not observed in women. Results from this controlled feeding study suggest that men and women have similar effects from the MedDiet on systemic inflammation. The individual's overall inflammatory status seems to influence these effects, but only in men. This clinical trial was registered at www.clinicaltrials.gov as NCT01293344 .

High invertase activity in tomato reproductive organs correlates with enhanced sucrose import into, and heat tolerance of, young fruit.

PubMed

Li, Zhimiao; Palmer, William M; Martin, Antony P; Wang, Rongqing; Rainsford, Frederick; Jin, Ye; Patrick, John W; Yang, Yuejian; Ruan, Yong-Ling

2012-02-01

Heat stress can cause severe crop yield losses by impairing reproductive development. However, the underlying mechanisms are poorly understood. We examined patterns of carbon allocation and activities of sucrose cleavage enzymes in heat-tolerant (HT) and -sensitive (HS) tomato (Solanum lycopersicum L.) lines subjected to normal (control) and heat stress temperatures. At the control temperature of 25/20 °C (day/night) the HT line exhibited higher cell wall invertase (CWIN) activity in flowers and young fruits and partitioned more sucrose to fruits but less to vegetative tissues as compared to the HS line, independent of leaf photosynthetic capacity. Upon 2-, 4-, or 24-h exposure to day or night temperatures of 5 °C or more above 25/20 °C, cell wall (CWIN) and vacuolar invertases (VIN), but not sucrose synthase (SuSy), activities in young fruit of the HT line were significantly higher than those of the HS line. The HT line had a higher level of transcript of a CWIN gene, Lin7, in 5-day fruit than the HS line under control and heat stress temperatures. Interestingly, heat induced transcription of an invertase inhibitor gene, INVINH1, but reduced its protein abundance. Transcript levels of LePLDa1, encoding phospholipase D, which degrades cell membranes, was less in the HT line than in the HS line after exposure to heat stress. The data indicate that high invertase activity of, and increased sucrose import into, young tomato fruit could contribute to their heat tolerance through increasing sink strength and sugar signalling activities, possibly regulating a programmed cell death pathway.

Histone modifications in the male germ line of Drosophila.

PubMed

Hennig, Wolfgang; Weyrich, Alexandra

2013-02-22

In the male germ line of Drosophila chromatin remains decondensed and highly transcribed during meiotic prophase until it is rapidly compacted. A large proportion of the cell cycle-regulated histone H3.1 is replaced by H3.3, a histone variant encoded outside the histone repeat cluster and not subject to cell cycle controlled expression. We investigated histone modification patterns in testes of D. melanogaster and D. hydei. In somatic cells of the testis envelope and in germ cells these modification patterns differ from those typically seen in eu- and heterochromatin of other somatic cells. During the meiotic prophase some modifications expected in active chromatin are not found or are found at low level. The absence of H4K16ac suggests that dosage compensation does not take place. Certain histone modifications correspond to either the cell cycle-regulated histone H3.1 or to the testis-specific variant H3.3. In spermatogonia we found H3K9 methylation in cytoplasmic histones, most likely corresponding to the H3.3 histone variant. Most histone modifications persist throughout the meiotic divisions. The majority of modifications persist until the early spermatid nuclei, and only a minority further persist until the final chromatin compaction stages before individualization of the spermatozoa. Histone modification patterns in the male germ line differ from expected patterns. They are consistent with an absence of dosage compensation of the X chromosome during the male meiotic prophase. The cell cycle-regulated histone variant H3.1 and H3.3, expressed throughout the cell cycle, also vary in their modification patterns. Postmeiotically, we observed a highly complex pattern of the histone modifications until late spermatid nuclear elongation stages. This may be in part due to postmeiotic transcription and in part to differential histone replacement during chromatin condensation.

Interaction of the amyloid precursor protein-like protein 1 (APLP1) E2 domain with heparan sulfate involves two distinct binding modes

DOE Office of Scientific and Technical Information (OSTI.GOV)

Dahms, Sven O., E-mail: sdahms@fli-leibniz.de; Mayer, Magnus C.; Miltenyi Biotec GmbH, Robert-Koch-Strasse 1, 17166 Teterow

2015-03-01

Two X-ray structures of APLP1 E2 with and without a heparin dodecasaccharide are presented, revealing two distinct binding modes of the protein to heparan sulfate. The data provide a mechanistic explanation of how APP-like proteins bind to heparan sulfates and how they specifically recognize nonreducing structures of heparan sulfates. Beyond the pathology of Alzheimer’s disease, the members of the amyloid precursor protein (APP) family are essential for neuronal development and cell homeostasis in mammals. APP and its paralogues APP-like protein 1 (APLP1) and APP-like protein 2 (APLP2) contain the highly conserved heparan sulfate (HS) binding domain E2, which effects variousmore » (patho)physiological functions. Here, two crystal structures of the E2 domain of APLP1 are presented in the apo form and in complex with a heparin dodecasaccharide at 2.5 Å resolution. The apo structure of APLP1 E2 revealed an unfolded and hence flexible N-terminal helix αA. The (APLP1 E2){sub 2}–(heparin){sub 2} complex structure revealed two distinct binding modes, with APLP1 E2 explicitly recognizing the heparin terminus but also interacting with a continuous heparin chain. The latter only requires a certain register of the sugar moieties that fits to a positively charged surface patch and contributes to the general heparin-binding capability of APP-family proteins. Terminal binding of APLP1 E2 to heparin specifically involves a structure of the nonreducing end that is very similar to heparanase-processed HS chains. These data reveal a conserved mechanism for the binding of APP-family proteins to HS and imply a specific regulatory role of HS modifications in the biology of APP and APP-like proteins.« less

Bacillus anthracis Prolyl 4-Hydroxylase Interacts with and Modifies Elongation Factor Tu

DOE Office of Scientific and Technical Information (OSTI.GOV)

Schnicker, Nicholas J.; Razzaghi, Mortezaali; Guha Thakurta, Sanjukta

Prolyl hydroxylation is a very common post-translational modification and plays many roles in eukaryotes such as collagen stabilization, hypoxia sensing, and controlling protein transcription and translation. There is a growing body of evidence that suggests that prokaryotes contain prolyl 4-hydroxylases (P4Hs) homologous to the hypoxia-inducible factor (HIF) prolyl hydroxylase domain (PHD) enzymes that act on elongation factor Tu (EFTu) and are likely involved in the regulation of bacterial translation. Recent biochemical and structural studies with a PHD from Pseudomonas putida (PPHD) determined that it forms a complex with EFTu and hydroxylates a prolyl residue of EFTu. Moreover, while animal, plant,more » and viral P4Hs act on peptidyl proline, most prokaryotic P4Hs have been known to target free l-proline; the exceptions include PPHD and a P4H from Bacillus anthracis (BaP4H) that modifies collagen-like proline-rich peptides. Here we use biophysical and mass spectrometric methods to demonstrate that BaP4H recognizes full-length BaEFTu and a BaEFTu 9-mer peptide for site-specific proline hydroxylation. Using size-exclusion chromatography coupled small-angle X-ray scattering (SEC–SAXS) and binding studies, we determined that BaP4H forms a 1:1 heterodimeric complex with BaEFTu. The SEC–SAXS studies reveal dissociation of BaP4H dimeric subunits upon interaction with BaEFTu. While BaP4H is unusual within bacteria in that it is structurally and functionally similar to the animal PHDs and collagen P4Hs, respectively, this work provides further evidence of its promiscuous substrate recognition. It is possible that the enzyme might have evolved to hydroxylate a universally conserved protein in prokaryotes, similar to the PHDs, and implies a functional role in B. anthracis.« less

HS-SPME/GC analysis reveals the population variability of terpene contents in Juniperus communis needles.

PubMed

Filipowicz, Natalia; Madanecki, Piotr; Gołebiowski, Marek; Stepnowski, Piotr; Ochocka, J Renata

2009-12-01

Juniperus communis var. communis L. is an aromatic plant - typical boreal element of flora. In the extensive literature concerning J. communis, there is much data on the composition and the content of essential oil of needles and coneberries, but a detailed analysis of terpene distribution within and between populations is missing. A representative pool of 74 J. communis individuals originating from ten populations of Northern Poland was investigated in order to evaluate the intra- and interpopulational variability of the terpene pattern. Headspace solid-phase microextraction (HS-SPME) coupled with GC/MS and GC/FID was applied in achiral and enantioselective analysis. The majority of the samples (85%), despite different origin, were similar in the terpene pattern. High diversity of terpenes was observed within the populations and low diversity between them. High variation of enantiomeric composition was in accordance with large variation of individual compounds in general (achiral analysis). J. communis samples from Northern Poland could be distinguished by the alpha-pinene/sabinene ratio, and they were divided into three chemical races.

Can solar cycle modulate the ENSO effect on the Pacific/North American pattern?

NASA Astrophysics Data System (ADS)

Li, Delin; Xiao, Ziniu

2018-01-01

The ENSO effect on the Pacific/North American pattern (PNA) is well-known robust. Recent studies from observations and model simulations have reported that some important atmospheric circulation systems of extratropics are markedly modulated by the 11-year solar cycle. But less effort has been devoted to revealing the solar influence on the PNA. We thus hypothesize that the instability and uncertainty in the relationship between solar activity and PNA could be due to the ENSO impacts. In this study, solar cycle modulation of the ENSO effect on the PNA has been statistically examined by the observations from NOAA and NCEP/NCAR for the period of 1950-2014. Results indicate that during the high solar activity (HS) years, the PNA has stronger relevance to the ENSO, and the response of tropospheric geopotential height to ENSO variability is broadly similar to the typical positive PNA pattern. However, in the case of low solar activity (LS) years, the correlation between ENSO and PNA decreases relatively and the response has some resemblance to the negative phase of Arctic Oscillation (AO). Also, we find the impacts of solar activity on the middle troposphere are asymmetric during the different solar cycle phases, and the weak PNA-like response to solar activity only presents in the HS years. Closer inspection suggests that the higher solar activity has a much more remarkable modulation on the PNA-like response to the warm ENSO (WE) than that to the cold ENSO (CE), particularly over the Northeast Pacific region. The possible cause of the different responses might be the solar influence on the subtropical westerlies of upper troposphere. When the sea surface temperature (SST) of east-central tropical Pacific is anomalously warm, the upper tropospheric westerlies are significantly modulated by the higher solar activity, resulting in the acceleration and eastward shift of the North Pacific subtropical jet, which favors the propagation of WE signal from the tropical Pacific to the North Pacific, and consequently leading to the development of positive PNA-like pattern during the WE phase. Thus, it seems that the solar cycle can significantly modulate the WE effect on the PNA under the HS background.

Clinical and electrophysiological findings in mesial temporal lobe epilepsy with hippocampal sclerosis, based on the recent histopathological classifications.

PubMed

Tezer, F Irsel; Xasiyev, Farid; Soylemezoglu, Figen; Bilginer, Burcak; Oguz, Kader Karli; Saygi, Serap

2016-11-01

Hippocampal sclerosis (HS) is a common pathology in MTLE, patients may show different surgical outcomes and clinical features. The 2013 ILAE classification subdivides HS into 3 types (HS type 1: severe neuronal loss and gliosis predominantly in CA1 and CA4 regions; - HS type 2: CA1 predominant; HS type 3: CA4 predominant) and includes "gliosis only, as no-HS". The association of clinical and electrophysiological findings with different HS types has not been reported previously in detail. 48 patients who had undergone temporal lobectomy with amygdalohippocampectomy due to mesial TLE-HS between February 2014 and February 2016 were included. The patients were divided into five groups: patients with HS ILAE type 1, HS ILAE type 2, HS ILAE type 3, FCD type IIIa, or gliosis/no HS. The correlation between HS ILAE types and clinical/EEG findings in patients with MTLE due to HS was investigated. Of the 48 patients 30 were male. In 23 patients, the resection was on the left side (48%). Three patients had only gliosis, 25 patients had HS ILAE type 1, 7 had HS ILAE type 2, and 4 had HS ILAE type 3. Nine of the 48 patients had cortical lamination abnormalities in the temporal lobe associated with HS (FCD type IIIa). All patients were seizure free for early follow up. There was no association between type of HS in terms of duration of epilepsy, onset age of epilepsy, lateralized or localized semiological findings, or interictal/ictal EEG findings. Family history of epilepsy or SGTCSs were statistically more frequent in patients with types 2 and 3 HS and status epilepticus was more frequent in patients with HS-FCD type IIIa. The patients with HS types 2 and 3 have more frequent SGTCS or status epilepticus as well as increased family history of epilepsy. These findings can be helpful in understanding the epileptogenicity-prognoses of HS. Copyright © 2016 Elsevier B.V. All rights reserved.

Microscopic mild focal cortical dysplasia in temporal lobe dual pathology: an electrocorticography study.

PubMed

Morales Chacón, L; Estupiñán, B; Lorigados Pedre, L; Trápaga Quincoses, O; García Maeso, I; Sanchez, A; Bender del Busto, J; Garcia, M E; Baez Martin, M; Zaldivar, M; Gómez, A; Orozco, S; Rocha Arrieta, L

2009-10-01

Associations between electrophysiological and histological findings might provide an insight into the epileptogenicity of mild focal cortical dysplasia (FCD) in patients with temporal lobe epilepsy (TLE) and a dual pathology. A total of 22 patients with pharmacoresistant TLE were included in the study, 16 of them with histologically confirmed hippocampal sclerosis (HS) associated with neocortical temporal mild Palmini Type-I FCD subtypes and 6 with HS. Intraoperative electrocorticography (ECoG) recordings were analysed for epileptiform discharge frequency and morphology. Associations between histological, and electrocorticography pattern findings in these patients were analysed. Electroclinical outcomes in these patients were also evaluated. Neocortical areas with mild Palmini Type-I FCD showed a significantly higher spike frequency (SF) recorded in the inferior temporal gyrus than those neocortical areas in patients with HS. There was a tendency to higher spike frequency and lower amplitude in neocortical areas with histopathologic subtype IB FCD in relation with IA during intraoperative ECoG. Post-SF excision and amplitude were significantly lower during neocortical post-excision intraoperative ECoG than during neocortical pre-excision recording. There was no difference found in the clinical outcome between patients with and without FCD. Intraoperative electrocorticographic interictal spike frequency recorded in the neocortical inferior temporal gyrus may help to characterize the histopathologic subtypes of mild Palmini Type-I FCD in patients with temporal lobe epilepsy (TLE) and a dual pathology. Our data support the epileptogenicity of neocortical mild FCD in TLE and assessments of ECoG patterns are relevant to determine the extent of the resection in these patients which can influence the electroclinical outcome.

Effects of humic substances supplementation provided through drinking water on performance, carcass traits and meat quality of broilers.

PubMed

Ozturk, E; Ocak, N; Coskun, I; Turhan, S; Erener, G

2010-02-01

The present study aimed at evaluating the effects of different doses of humic substances (HS) in waterer pan on broiler performances and meat quality. For the trial, 480 chicks (ROSS 308) were allocated into four groups (HS0, HS150, HS300 and HS450) of 120 equally mixed-sex birds, each receiving a drinking water supplemented with 0, 150, 300 and 450 ppm of a humic acid (provided by 0.0%, 0.5%, 1.0% and 1.5% of HS, v/v) respectively. At the age of 21 and 42 days, feed consumption and live weight were taken. At the age of 42 days, 16 birds per treatment were slaughtered, dressing percentages, digestive tract traits were evaluated and samples of breast (pectoralis major) and thigh (iliotibialis) meat were taken to evaluate the changes in colour characteristics (CIE L*, a* and b*) and chemical composition. The body weight gain increased by the HS300 in relation to the HS0 and HS450, and decreased by the HS450 in relation to the HS0. The feed consumption of birds in the HS450 and feed efficiency of birds in the HS300 were lower and higher than those in the other treatments respectively. The carcass weight of broilers in the HS150 and HS300 were higher than those of in the HS0 and HS450. The carcass weight decreased by the HS450 in relation to the other treatments. The dressing percentage increased by the HS150 in relation to the HS450. The HS450 resulted in breast and thigh meat colour that were lighter than those found in the HS0 birds. The HS450 increased fat content of thigh meat in relation to the HS0. It was concluded that the humic acid supplementation at 300 ppm and 450 ppm appears to have a measurable impact on live performance improving feed efficiency and lightness of breast and thigh meat colours in broilers respectively.

Effect of dietary starch level and high rumen-undegradable protein on endocrine-metabolic status, milk yield, and milk composition in dairy cows during early and late lactation.

PubMed

Piccioli-Cappelli, F; Loor, J J; Seal, C J; Minuti, A; Trevisi, E

2014-12-01

Diet composition defines the amount and type of nutrients absorbed by dairy cows. Endocrine-metabolic interactions can influence these parameters, and so nutrient availability for the mammary gland can significantly vary and affect milk yield and its composition. Six dairy cows in early and then late lactation received, for 28 d in a changeover design, 2 diets designed to provide, within the same stage of lactation, similar amounts of rumen fermentable material but either high starch plus sugar (HS) content or low starch plus sugar content (LS). All diets had similar dietary crude protein and calculated supply of essential amino acids. Dry matter intake within each stage of lactation was similar between groups. Milk yield was similar between groups in early lactation, whereas a higher milk yield was observed in late lactation when feeding HS. At the metabolic level, the main difference observed between the diets in both stages of lactation was lower blood glucose in cows fed LS. The lower glucose availability during consumption of LS caused substantial modifications in the circulating and postprandial pattern of metabolic hormones. Feeding LS versus HS resulted in an increase in the ratio of bovine somatotropin to insulin. This increased mobilization of lipid reserves resulted in higher blood concentrations of nonesterified fatty acids and β-hydroxybutyrate, which contributed to the higher milk fat content in both stages of lactation in the LS group. This greater recourse to body fat stores was confirmed by the greater loss of body weight during early lactation and the slower recovery of body weight in late lactation in cows fed LS. The lower insulin to glucagon ratio observed in cows fed LS in early and late lactation likely caused an increase in hepatic uptake and catabolism of amino acids, as confirmed by the higher blood urea concentrations. Despite the higher catabolism of amino acids in LS in early lactation, similar milk protein output was observed for both diets, suggesting similar availability of amino acids for peripheral tissue and mammary gland. The latter could be the result of sparing of amino acids at the gut level due to starch that escaped from the rumen, and to the balanced amino acid profile of digestible protein. This last aspect appears worthy of further research, with the aim to enhance the efficiency of protein metabolism of dairy cows, reducing environmental nitrogen pollution without affecting milk yield potential.

A histological study on the effect of pressure therapy on the activities of myofibroblasts and keratinocytes in hypertrophic scar tissues after burn.

PubMed

Li-Tsang, Cecilia W P; Feng, Beibei; Huang, Lin; Liu, Xusheng; Shu, Bin; Chan, Yvonne T Y; Cheung, Kwok-Kuen

2015-08-01

Although pressure therapy (PT) has been widely used as the first-line treatment for hypertrophic scars (HS), the histopathological changes involved have seldom been studied. This study aimed to examine the longitudinal effect of PT on the histopathological changes in HS. Ten scar samples were selected from six patients with HS after burn and they were given a standardized PT intervention for 3 months while 16 scar samples were obtained on those without PT. The scar biopsies were collected pre-treatment, 1 and 3 months post-intervention for both clinical and histopathological examinations. Clinical assessments demonstrated significant improvement in the thickness and redness of the scars after PT. Histological examination revealed that cell density in the dermal layer was markedly reduced in the 3-months post-pressurized scar tissues, while the arrangement of the collagen fiber was changed from nodular to wave-like pattern. The α-smooth muscle actin immunoreactivity was significantly decreased after 1-month pressure treatment. There was a significant reduction of myofibroblasts population and a concomitant increase in the apoptotic index in the dermal layer in the 3-months' post-pressurized scars. A significant negative correlation was found between the myofibroblasts population and the apoptotic index. The keratinocyte proliferation was found inhibited after PT. Results demonstrated that PT appeared to promote HS maturation by inhibiting the keratinocyte proliferation and suppressing myofibroblasts population, the latter possibly via apoptosis. Copyright © 2014 Elsevier Ltd and ISBI. All rights reserved.

A proximal promoter region of Arabidopsis DREB2C confers tissue-specific expression under heat stress.

PubMed

Chen, Huan; Je, Jihyun; Song, Chieun; Hwang, Jung Eun; Lim, Chae Oh

2012-09-01

The dehydration-responsive element-binding factor 2C (DREB2C) is a member of the CBF/DREB subfamily of proteins, which contains a single APETALA2/Ethylene responsive element-binding factor (AP2/ERF) domain. To identify the expression pattern of the DREB2C gene, which contains multiple transcription cis-regulatory elements in its promoter, an approximately 1.4 kb upstream DREB2C sequence was fused to the β-glucuronidase reporter gene (GUS) and the recombinant p1244 construct was transformed into Arabidopsis thaliana (L.) Heynh. The promoter of the gene directed prominent GUS activity in the vasculature in diverse young dividing tissues. Upon applying heat stress (HS), GUS staining was also enhanced in the vasculature of the growing tissues. Analysis of a series of 5'-deletions of the DREB2C promoter revealed that a proximal upstream sequence sufficient for the tissue-specific spatial and temporal induction of GUS expression by HS is localized in the promoter region between -204 and -34 bps relative to the transcriptional start site. Furthermore, electrophoretic mobility shift assay (EMSA) demonstrated that nuclear protein binding activities specific to a -120 to -32 bp promoter fragment increased after HS. These results indicate that the TATA-proximal region and some latent trans-acting factors may cooperate in HS-induced activation of the Arabidopsis DREB2C promoter. © 2012 Institute of Botany, Chinese Academy of Sciences.

Insight into infection-mediated prostate damage: Contrasting patterns of C-reactive protein and prostate-specific antigen levels during infection.

PubMed

Milbrandt, Melissa; Winter, Anke C; Nevin, Remington L; Pakpahan, Ratna; Bradwin, Gary; De Marzo, Angelo M; Elliott, Debra J; Gaydos, Charlotte A; Isaacs, William B; Nelson, William G; Rifai, Nader; Sokoll, Lori J; Zenilman, Jonathan M; Platz, Elizabeth A; Sutcliffe, Siobhan

2017-05-01

To investigate mechanisms underlying our previous observation of a large rise in serum prostate-specific antigen, a marker of prostate pathology, during both sexually transmitted and systemic infections, we measured serum high-sensitivity C-reactive protein (hsCRP), a marker of systemic inflammation, in our previous case-control study of young, male US military members and compared our findings to those for PSA. We measured hsCRP before and during infection for 299 chlamydia, 112 gonorrhea, and 59 non-chlamydial, non-gonococcal urethritis (NCNGU) cases; before and after infection for 55 infectious mononucleosis (IM) and 90 other systemic/non-genitourinary cases; and for 220-256 controls. Only gonorrhea cases were significantly more likely to have a large hsCRP rise (≥1.40 mg/L or ≥239%) during infection than controls (P < 0.01). However, gonorrhea, IM, and other systemic/non-genitourinary cases were more likely to have a rise of any magnitude up to one year post-diagnosis than controls (p = 0.038-0.077). These findings, which differ from those for PSA, suggest distinct mechanisms of elevation for hsCRP and PSA, and support both direct (eg, prostate infection) and indirect (eg, systemic inflammation-mediated prostate cell damage) mechanisms for PSA elevation. Future studies should explore our PSA findings further for their relevance to both prostate cancer screening and risk. © 2017 Wiley Periodicals, Inc.

HsTRPA of the Red Imported Fire Ant, Solenopsis invicta, Functions as a Nocisensor and Uncovers the Evolutionary Plasticity of HsTRPA Channels

PubMed Central

Wang, Xinyue; Li, Tianbang; Tominaga, Makoto

2018-01-01

Solenopsis invicta, the red imported fire ant, represents one of the most devastating invasive species. To understand their sensory physiology, we identified and characterized their Hymenoptera-specific (Hs) TRPA channel, SiHsTRPA. Consistent with the sensory functions of SiHsTRPA, it is activated by heat, an electrophile, and an insect repellent. Nevertheless, SiHsTRPA does not respond to most of the honey bee ortholog (AmHsTRPA)-activating compounds. The jewel wasp ortholog (NvHsTRPA) is activated by these compounds even though it outgroups both AmHsTRPA and SiHsTRPA. Characterization of AmHsTRPA/SiHsTRPA chimeric channels revealed that the amino acids in the N terminus, as well as ankyrin repeat 2 (AR2) of AmHsTRPA, are essential for the response to camphor. Furthermore, amino acids in ARs 3 and 5–7 were specifically required for the response to diallyl disulfide. Thus, amino acid substitutions in the corresponding domains of SiHsTRPA during evolution would be responsible for the loss of chemical sensitivity. SiHsTRPA-activating compounds repel red imported fire ants, suggesting that SiHsTRPA functions as a sensor for noxious compounds. SiHsTRPA represents an example of the species-specific modulation of orthologous TRPA channel properties by amino acid substitutions in multiple domains, and SiHsTRPA-activating compounds could be used to develop a method for controlling red imported fire ants. PMID:29445768

Ig synthesis and class switching do not require the presence of the hs4 enhancer in the 3' IgH regulatory region.

PubMed

Vincent-Fabert, Christelle; Truffinet, Véronique; Fiancette, Remi; Cogné, Nadine; Cogné, Michel; Denizot, Yves

2009-06-01

Several studies have reported that regulatory elements located 3' of the IgH locus (namely hs3a, hs1,2, hs3b, and hs4) might play a role during class switch recombination (CSR) and Ig synthesis. While individual deletion of hs3a or hs1,2 had no effect, pairwise deletion of hs3b (an inverted copy of hs3a) and hs4 markedly affected CSR and Ig expression. Among these two elements, hs4 was tentatively presented with the master role due to its unique status within the 3' regulatory region: distal position outside repeated regions, early activation in pre-B cells, strong activity throughout B cell ontogeny. To clarify its role, we generated mice with a clean deletion of the hs4 after replacement with a floxed neo(R) cassette. Surprisingly, and as for previous deletion of hs3a or hs1,2, deletion of hs4 did not affect either in vivo CSR or the secretion level of any Ig isotype. In vitro CSR and Ig secretion in response to LPS and cytokines was not affected either. The only noticeable effects of the hs4 deletion were a decrease in the number of B splenocytes and a decreased membrane IgM expression. In conclusion, while dispensable for CSR and Ig transcription in plasma cells, hs4 mostly appears to contribute to Ig transcription in resting B lymphocytes.

An effective hybrid firefly algorithm with harmony search for global numerical optimization.

PubMed

Guo, Lihong; Wang, Gai-Ge; Wang, Heqi; Wang, Dinan

2013-01-01

A hybrid metaheuristic approach by hybridizing harmony search (HS) and firefly algorithm (FA), namely, HS/FA, is proposed to solve function optimization. In HS/FA, the exploration of HS and the exploitation of FA are fully exerted, so HS/FA has a faster convergence speed than HS and FA. Also, top fireflies scheme is introduced to reduce running time, and HS is utilized to mutate between fireflies when updating fireflies. The HS/FA method is verified by various benchmarks. From the experiments, the implementation of HS/FA is better than the standard FA and other eight optimization methods.

Assessing Transformations of Algal Organic Matter in the Long-Term: Impacts of Humification-Like Processes

PubMed Central

Leloup, Maud; Pallier, Virginie; Nicolau, Rudy; Feuillade-Cathalifaud, Geneviève

2015-01-01

Algae and cyanobacteria are important contributors to the natural organic matter (NOM) of eutrophic water resources. The objective of this work is to increase knowledge on the modifications of algal organic matter (AOM) properties in the long term to anticipate blooms footprint in such aquatic environments. The production of AOM from an alga (Euglena gracilis) and a cyanobacteria (Microcystis aeruginosa) was followed up and characterized during the stationary phase and after one year and four months of cultivation, in batch experiments. Specific UV absorbance (SUVA) index, organic matter fractionation according to hydrophobicity and apparent molecular weight were combined to assess the evolution of AOM. A comparison between humic substances (HS) mainly derived from allochthonous origins and AOM characteristics was performed to hypothesize impacts of AOM transformation processes on the water quality of eutrophic water resources. Each AOM fraction underwent a specific evolution pattern, depending on its composition. Impacts of humification-like processes were predominant over release of biopolymers due to cells decay and led to an increase in the hydrophobic compounds part and molecular weights over time. However, the hydrophilic fraction remained the major fraction whatever the growth stage. Organic compounds generated by maturation of these precursors corresponded to large and aliphatic structures. PMID:26251898

The inadequacy of Individual Educational Program (IEP) goals for high school students with word-level reading difficulties.

PubMed

Catone, William V; Brady, Susan A

2005-06-01

This investigation analyzed goals from the Individual Educational Programs (IEPs) of 54 high school students with diagnosed reading disabilities in basic skills (decoding and/or word identification). Results showed that for 73% of the students, the IEPs written when they were in high school failed to specify any objectives regarding their acute difficulties with basic skills. IEPs from earlier points in the students' educations were also reviewed, as available. For 23 of the students, IEPs were present in the students' files for three time points: elementary school (ES), middle school (MS), and high school (HS). Another 20 students from the sample of 54 had IEPs available for two time points (HS and either MS or ES). Comparisons with the IEPs from younger years showed a pattern of decline from ES to MS to HS in the percentage of IEPs that commented on or set goals pertaining to weaknesses in decoding. These findings suggest that basic skills deficits that persist into the upper grade levels are not being sufficiently targeted for remediation, and help explain why older students frequently fail to resolve their reading problems.

In vivo use of hyperspectral imaging to develop a noncontact endoscopic diagnosis support system for malignant colorectal tumors

NASA Astrophysics Data System (ADS)

Han, Zhimin; Zhang, Aoyu; Wang, Xiguang; Sun, Zongxiao; Wang, May D.; Xie, Tianyu

2016-01-01

The early detection and diagnosis of malignant colorectal tumors enables the initiation of early-stage therapy and can significantly increase the survival rate and post-treatment quality of life among cancer patients. Hyperspectral imaging (HSI) is recognized as a powerful tool for noninvasive cancer detection. In the gastrointestinal field, most of the studies on HSI have involved ex vivo biopsies or resected tissues. In the present study, we aimed to assess the difference in the in vivo spectral reflectance of malignant colorectal tumors and normal mucosa. A total of 21 colorectal tumors or adenomatous polyps from 12 patients at Shanghai Zhongshan Hospital were examined using a flexible hyperspectral (HS) colonoscopy system that can obtain in vivo HS images of the colorectal mucosa. We determined the optimal wavelengths for differentiating tumors from normal tissue based on these recorded images. The application of the determined wavelengths in spectral imaging in clinical trials indicated that such a clinical support system comprising a flexible HS colonoscopy unit and band selection unit is useful for outlining the tumor region and enhancing the display of the mucosa microvascular pattern in vivo.

An Effective Hybrid Firefly Algorithm with Harmony Search for Global Numerical Optimization

PubMed Central

Guo, Lihong; Wang, Gai-Ge; Wang, Heqi; Wang, Dinan

2013-01-01

A hybrid metaheuristic approach by hybridizing harmony search (HS) and firefly algorithm (FA), namely, HS/FA, is proposed to solve function optimization. In HS/FA, the exploration of HS and the exploitation of FA are fully exerted, so HS/FA has a faster convergence speed than HS and FA. Also, top fireflies scheme is introduced to reduce running time, and HS is utilized to mutate between fireflies when updating fireflies. The HS/FA method is verified by various benchmarks. From the experiments, the implementation of HS/FA is better than the standard FA and other eight optimization methods. PMID:24348137

Calcified neurocysticercosis lesions and hippocampal sclerosis: potential dual pathology?

PubMed

Rathore, Chaturbhuj; Thomas, Bejoy; Kesavadas, Chandrasekharan; Radhakrishnan, Kurupath

2012-04-01

In areas where cysticercosis is endemic, calcified neurocysticercosis lesion(s) (CNL) and hippocampal sclerosis (HS) commonly coexist in patients with localization-related epilepsies. To understand the pathogenesis of HS associated with CNL, we compared the characteristics of three groups of patients with antiepileptic drug-resistant epilepsies: CNL with HS, CNL without HS (CNL alone), and HS without CNL (HS alone). In comparison to patients with CNL alone, those with CNL with HS had CNL more frequently located in the ipsilateral temporal lobe. Those with CNL with HS had a lower incidence of febrile seizures, older age at initial precipitating injury and at onset of habitual complex partial seizures, and more frequent clustering of seizures and extratemporal/bitemporal interictal epileptiform discharges as compared to patients with HS alone. Our study illustrates that HS associated with CNL might have a different pathophysiologic basis as compared to classical HS. Wiley Periodicals, Inc. © 2012 International League Against Epilepsy.

Molecular identification and functional characterization of the first Nα-acetyltransferase in plastids by global acetylome profiling.

PubMed

Dinh, Trinh V; Bienvenut, Willy V; Linster, Eric; Feldman-Salit, Anna; Jung, Vincent A; Meinnel, Thierry; Hell, Rüdiger; Giglione, Carmela; Wirtz, Markus

2015-07-01

Protein N(α) -terminal acetylation represents one of the most abundant protein modifications of higher eukaryotes. In humans, six N(α) -acetyltransferases (Nats) are responsible for the acetylation of approximately 80% of the cytosolic proteins. N-terminal protein acetylation has not been evidenced in organelles of metazoans, but in higher plants is a widespread modification not only in the cytosol but also in the chloroplast. In this study, we identify and characterize the first organellar-localized Nat in eukaryotes. A primary sequence-based search in Arabidopsis thaliana revealed seven putatively plastid-localized Nats of which AT2G39000 (AtNAA70) showed the highest conservation of the acetyl-CoA binding pocket. The chloroplastic localization of AtNAA70 was demonstrated by transient expression of AtNAA70:YFP in Arabidopsis mesophyll protoplasts. Homology modeling uncovered a significant conservation of tertiary structural elements between human HsNAA50 and AtNAA70. The in vivo acetylation activity of AtNAA70 was demonstrated on a number of distinct protein N(α) -termini with a newly established global acetylome profiling test after expression of AtNAA70 in E. coli. AtNAA70 predominately acetylated proteins starting with M, A, S and T, providing an explanation for most protein N-termini acetylation events found in chloroplasts. Like HsNAA50, AtNAA70 displays N(ε) -acetyltransferase activity on three internal lysine residues. All MS data have been deposited in the ProteomeXchange with identifier PXD001947 (http://proteomecentral.proteomexchange.org/dataset/PXD001947). © 2015 The Authors. PROTEOMICS Published by Wiley-VCH Verlag GmbH & Co. KGaA, Weinheim.

Rapid rule out of acute myocardial infarction using undetectable levels of high-sensitivity cardiac troponin.

PubMed

Rubini Giménez, Maria; Hoeller, Rebeca; Reichlin, Tobias; Zellweger, Christa; Twerenbold, Raphael; Reiter, Miriam; Moehring, Berit; Wildi, Karin; Mosimann, Tamina; Mueller, Mira; Meller, Bernadette; Hochgruber, Thomas; Ziller, Ronny; Sou, Seoung Mann; Murray, Karsten; Sakarikos, Konstantin; Ernst, Susanne; Gea, Joaquim; Campodarve, Isabel; Vilaplana, Carles; Haaf, Philip; Steuer, Stephan; Minners, Jan; Osswald, Stefan; Mueller, Christian

2013-10-09

We examined whether undetectable levels of high-sensitivity cardiac Troponin (hs-cTn) can be used to rule out acute myocardial infarction (AMI) with a single blood draw at presentation to the emergency department (ED). In a prospective multicenter study we used 4 different hs-cTn assays (hs-cTnT Roche, and hs-cTnI Siemens, hs-cTnI Beckman Coulter and hs-cTnI Abbott) in consecutive patients presenting with acute chest pain. The final diagnosis of AMI was adjudicated by two independent cardiologists using all available data including serial hs-cTnT levels. Mean follow up was 24 months. Among 2072 consecutive patients with available hs-cTnT levels, 21% had an adjudicated diagnosis of AMI. Among AMI patients, 98.2% had initially detectable levels of hs-cTnT (sensitivity 98.2%, 95%CI 96.3%-99.2%, negative predictive value (NPV) 98.6%, 95%CI 97.0%-99.3%). Undetectable levels of hs-cTnT ruled out AMI in 26.5% of patients at presentation. The NPV was similar with the three hs-cTnI assays: among 1180 consecutive patients with available hs-cTnI (Siemens), the NPV was 98.8%; among 1151 consecutive patients with available hs-cTnI (Beckman Coulter), the NPV was 99.2%; among 1567 consecutive patients with available hs-cTnI (Abbott), the NPV was 100.0%. The percentage of patients with undetectable levels of hs-cTnI was similar among the three hs-cTnI assays and ranged from 11.4% to 13.9%. Undetectable levels of hs-cTn at presentation have a very high NPV and seem to allow the simple and rapid rule out of AMI. This criteria applies to much more patients with hs-TnT as compared to the investigated hs-cTnI assays. © 2013.

Modeling heat stress under different environmental conditions.

PubMed

Carabaño, M J; Logar, B; Bormann, J; Minet, J; Vanrobays, M-L; Díaz, C; Tychon, B; Gengler, N; Hammami, H

2016-05-01

Renewed interest in heat stress effects on livestock productivity derives from climate change, which is expected to increase temperatures and the frequency of extreme weather events. This study aimed at evaluating the effect of temperature and humidity on milk production in highly selected dairy cattle populations across 3 European regions differing in climate and production systems to detect differences and similarities that can be used to optimize heat stress (HS) effect modeling. Milk, fat, and protein test day data from official milk recording for 1999 to 2010 in 4 Holstein populations located in the Walloon Region of Belgium (BEL), Luxembourg (LUX), Slovenia (SLO), and southern Spain (SPA) were merged with temperature and humidity data provided by the state meteorological agencies. After merging, the number of test day records/cows per trait ranged from 686,726/49,655 in SLO to 1,982,047/136,746 in BEL. Values for the daily average and maximum temperature-humidity index (THIavg and THImax) ranges for THIavg/THImax were largest in SLO (22-74/28-84) and shortest in SPA (39-76/46-83). Change point techniques were used to determine comfort thresholds, which differed across traits and climatic regions. Milk yield showed an inverted U-shaped pattern of response across the THI scale with a HS threshold around 73 THImax units. For fat and protein, thresholds were lower than for milk yield and were shifted around 6 THI units toward larger values in SPA compared with the other countries. Fat showed lower HS thresholds than protein traits in all countries. The traditional broken line model was compared with quadratic and cubic fits of the pattern of response in production to increasing heat loads. A cubic polynomial model allowing for individual variation in patterns of response and THIavg as heat load measure showed the best statistical features. Higher/lower producing animals showed less/more persistent production (quantity and quality) across the THI scale. The estimated correlations between comfort and THIavg values of 70 (which represents the upper end of the THIavg scale in BEL-LUX) were lower for BEL-LUX (0.70-0.80) than for SPA (0.83-0.85). Overall, animals producing in the more temperate climates and semi-extensive grazing systems of BEL and LUX showed HS at lower heat loads and more re-ranking across the THI scale than animals producing in the warmer climate and intensive indoor system of SPA. Copyright © 2016 American Dairy Science Association. Published by Elsevier Inc. All rights reserved.

Addendum to "Harmony of computational quantum chemistry and experimental chemistry: Comprehensive DFT studies, microsynthesis, and characterization of mustard gas polysulfide analogues" [J. Mol. Struct. (2018) 57-62

NASA Astrophysics Data System (ADS)

Saeidian, Hamid; Faraz, Sajjad Mousavi; Mirjafary, Zohreh; Babri, Mehran

2018-07-01

Recently, Blum from OPCW laboratory investigated HD, HS2, HS3 and higher polysulfides and their corresponding reactive intermediates by using Amsterdam Density Functional (ADF) calculations [22, 23]. In his presentation, he mentioned that analysis of MO energy levels for episulfonium ions of HD, HS2 and HS3 shows that the sulfur centered LUMOs for HS2 and HS3 are LUMO+1 for HD ion; and LUMOs energy levels of HS2 and HS3 are decreased by addition of polarizable sulfur atoms. He also showed that no four-membered sulfonium ion ring structures are formed for HS2, HS3 and higher polysulfides; and episulfonium ion is the only reactive intermediate for them.

Estimation of color modification in digital images by CFA pattern change.

PubMed

Choi, Chang-Hee; Lee, Hae-Yeoun; Lee, Heung-Kyu

2013-03-10

Extensive studies have been carried out for detecting image forgery such as copy-move, re-sampling, blurring, and contrast enhancement. Although color modification is a common forgery technique, there is no reported forensic method for detecting this type of manipulation. In this paper, we propose a novel algorithm for estimating color modification in images acquired from digital cameras when the images are modified. Most commercial digital cameras are equipped with a color filter array (CFA) for acquiring the color information of each pixel. As a result, the images acquired from such digital cameras include a trace from the CFA pattern. This pattern is composed of the basic red green blue (RGB) colors, and it is changed when color modification is carried out on the image. We designed an advanced intermediate value counting method for measuring the change in the CFA pattern and estimating the extent of color modification. The proposed method is verified experimentally by using 10,366 test images. The results confirmed the ability of the proposed method to estimate color modification with high accuracy. Copyright © 2012 Elsevier Ireland Ltd. All rights reserved.

Optimizing human activity patterns using global sensitivity analysis.

PubMed

Fairchild, Geoffrey; Hickmann, Kyle S; Mniszewski, Susan M; Del Valle, Sara Y; Hyman, James M

2014-12-01

Implementing realistic activity patterns for a population is crucial for modeling, for example, disease spread, supply and demand, and disaster response. Using the dynamic activity simulation engine, DASim, we generate schedules for a population that capture regular (e.g., working, eating, and sleeping) and irregular activities (e.g., shopping or going to the doctor). We use the sample entropy (SampEn) statistic to quantify a schedule's regularity for a population. We show how to tune an activity's regularity by adjusting SampEn, thereby making it possible to realistically design activities when creating a schedule. The tuning process sets up a computationally intractable high-dimensional optimization problem. To reduce the computational demand, we use Bayesian Gaussian process regression to compute global sensitivity indices and identify the parameters that have the greatest effect on the variance of SampEn. We use the harmony search (HS) global optimization algorithm to locate global optima. Our results show that HS combined with global sensitivity analysis can efficiently tune the SampEn statistic with few search iterations. We demonstrate how global sensitivity analysis can guide statistical emulation and global optimization algorithms to efficiently tune activities and generate realistic activity patterns. Though our tuning methods are applied to dynamic activity schedule generation, they are general and represent a significant step in the direction of automated tuning and optimization of high-dimensional computer simulations.

Optimizing human activity patterns using global sensitivity analysis

PubMed Central

Hickmann, Kyle S.; Mniszewski, Susan M.; Del Valle, Sara Y.; Hyman, James M.

2014-01-01

Implementing realistic activity patterns for a population is crucial for modeling, for example, disease spread, supply and demand, and disaster response. Using the dynamic activity simulation engine, DASim, we generate schedules for a population that capture regular (e.g., working, eating, and sleeping) and irregular activities (e.g., shopping or going to the doctor). We use the sample entropy (SampEn) statistic to quantify a schedule’s regularity for a population. We show how to tune an activity’s regularity by adjusting SampEn, thereby making it possible to realistically design activities when creating a schedule. The tuning process sets up a computationally intractable high-dimensional optimization problem. To reduce the computational demand, we use Bayesian Gaussian process regression to compute global sensitivity indices and identify the parameters that have the greatest effect on the variance of SampEn. We use the harmony search (HS) global optimization algorithm to locate global optima. Our results show that HS combined with global sensitivity analysis can efficiently tune the SampEn statistic with few search iterations. We demonstrate how global sensitivity analysis can guide statistical emulation and global optimization algorithms to efficiently tune activities and generate realistic activity patterns. Though our tuning methods are applied to dynamic activity schedule generation, they are general and represent a significant step in the direction of automated tuning and optimization of high-dimensional computer simulations. PMID:25580080

Optimizing human activity patterns using global sensitivity analysis

DOE PAGES

Fairchild, Geoffrey; Hickmann, Kyle S.; Mniszewski, Susan M.; ...

2013-12-10

Implementing realistic activity patterns for a population is crucial for modeling, for example, disease spread, supply and demand, and disaster response. Using the dynamic activity simulation engine, DASim, we generate schedules for a population that capture regular (e.g., working, eating, and sleeping) and irregular activities (e.g., shopping or going to the doctor). We use the sample entropy (SampEn) statistic to quantify a schedule’s regularity for a population. We show how to tune an activity’s regularity by adjusting SampEn, thereby making it possible to realistically design activities when creating a schedule. The tuning process sets up a computationally intractable high-dimensional optimizationmore » problem. To reduce the computational demand, we use Bayesian Gaussian process regression to compute global sensitivity indices and identify the parameters that have the greatest effect on the variance of SampEn. Here we use the harmony search (HS) global optimization algorithm to locate global optima. Our results show that HS combined with global sensitivity analysis can efficiently tune the SampEn statistic with few search iterations. We demonstrate how global sensitivity analysis can guide statistical emulation and global optimization algorithms to efficiently tune activities and generate realistic activity patterns. Finally, though our tuning methods are applied to dynamic activity schedule generation, they are general and represent a significant step in the direction of automated tuning and optimization of high-dimensional computer simulations.« less

β-Globin locus control region HS2 and HS3 interact structurally and functionally

PubMed Central

Jackson, David A.; McDowell, Jennifer C.; Dean, Ann

2003-01-01

The overall structure of the DNase I hypersensitive sites (HSs) that comprise the β-globin locus control region (LCR) is highly conserved among mammals, implying that the HSs have conserved functions. However, it is not well understood how the LCR HSs, either individually or collectively, activate transcription. We analyzed the interactions of HS2, HS3 and HS4 with the human ε- and β-globin genes in chromatinized episomes in fetal/embryonic K562 cells. Only HS2 activates transcription of the ε-globin gene, while all three HSs activate the β-globin gene. HS3 stimulates the β-globin gene constitutively, but HS2 and HS4 transactivation requires expression of the transcription factor EKLF, which is not present in K562 cells but is required for β-globin expression in vivo. To begin addressing how the individual HSs may interact with one another in a complex, we linked the β-globin gene to both the HS2 and HS3. HS2 and HS3 together resulted in synergistic stimulation of β-globin transcription. Unexpectedly, mutated, inactive forms of HS2 impeded the activation of the β-globin gene by HS3. Thus, there appear to be distinct interactions among the HSs and between the HSs and the globin genes. These preferential, non-exclusive interactions may underlie an important structural and functional cooperativity among the regulatory sequences of the β-globin locus in vivo. PMID:12582237

Tenotomy of m.soleus antagonists prevents the changes in fiber type characteristics and sarcomeric cytoskeletal proteins in unloaded rats

NASA Astrophysics Data System (ADS)

Moukhina, Alexandra; Ardabievskaya, Anna; Vikhlyantsev, Ivan; Podlubnaya, Zoya; Nemirovskaya, Tatiana; Shenkman, Boris

2005-08-01

It is known that activity of postural extensors (m. soleus) decreases and activity of flexors (m. tibialis anterior) increases under unloading conditions. We have tested the hypothesis supposing that increased flexor activities during unloading exert suppressive influence on postural extensor activities and thus lead to dramatic changes in fiber size, MHC expression, sarcomeric proteins content in m.soleus. We have inactivated hindlimb flexor muscles (m.soleus antagonists) by bilateral tenotomy. 20 male Wistar rats were divided on 3 groups: cage control (C), hindlimb suspension for 14 days (HS), tenotomy of hindlimb flexor muscles with 14 days hindlimb suspension afterwards (HST). Several soleus muscle fiber characteristics decreased significantly in HS group (p<0.05) as compared with C group: cross sectional area (CSA) of type I muscle fibers, titin/MyHC ratio and nebulin/MyHC ratio. MyHC isoform pattern shifted slow-to-fast significantly. NFATc1 content increased in nuclear protein extract of m. soleus in HS group. None of these parameters was significantly different in HST group from those of C group. It has been concluded that the tenotomy of flexors under hindlimb suspension prevents atrophy of type I muscle fibers, decrease the degradation of titin and nebulin and prevent slow-to-fast shift of fiber MyHC isoform pattern, possibly through prevention of increase NFATc1 content in muscle fiber nuclear protein extract. Therefore, suppressive influence of increased flexor activity could be one of mechanisms that lead to the changes in m. soleus under unloading conditions. The work was supported by RFBR grants: 02-04-50025, 03- 04-48487 and the special program of RAS "Integration mechanisms of functional control in the living system".

Thermal evolution of the western South Atlantic and the adjacent continent during Termination 1

NASA Astrophysics Data System (ADS)

Chiessi, C. M.; Mulitza, S.; Mollenhauer, G.; Silva, J. B.; Groeneveld, J.; Prange, M.

2015-06-01

During Termination 1, millennial-scale weakening events of the Atlantic meridional overturning circulation (AMOC) supposedly produced major changes in sea surface temperatures (SSTs) of the western South Atlantic, and in mean air temperatures (MATs) over southeastern South America. It has been suggested, for instance, that the Brazil Current (BC) would strengthen (weaken) and the North Brazil Current (NBC) would weaken (strengthen) during slowdown (speed-up) events of the AMOC. This anti-phase pattern was claimed to be a necessary response to the decreased North Atlantic heat piracy during periods of weak AMOC. However, the thermal evolution of the western South Atlantic and the adjacent continent is so far largely unknown. Here we address this issue, presenting high-temporal-resolution SST and MAT records from the BC and southeastern South America, respectively. We identify a warming in the western South Atlantic during Heinrich Stadial 1 (HS1), which is followed first by a drop and then by increasing temperatures during the Bølling-Allerød, in phase with an existing SST record from the NBC. Additionally, a similar SST evolution is shown by a southernmost eastern South Atlantic record, suggesting a South Atlantic-wide pattern in SST evolution during most of Termination 1. Over southeastern South America, our MAT record shows a two-step increase during Termination 1, synchronous with atmospheric CO2 rise (i.e., during the second half of HS1 and during the Younger Dryas), and lagging abrupt SST changes by several thousand years. This delay corroborates the notion that the long duration of HS1 was fundamental in driving the Earth out of the last glacial.

Thermal evolution of the western South Atlantic and the adjacent continent during Termination 1

NASA Astrophysics Data System (ADS)

Chiessi, C. M.; Mulitza, S.; Mollenhauer, G.; Silva, J. B.; Groeneveld, J.; Prange, M.

2014-12-01

During Termination 1, millennial-scale weakening events of the Atlantic meridional overturning circulation (AMOC) supposedly produced major changes in sea surface temperatures (SST) of the western South Atlantic, and in mean air temperatures (MAT) over southeastern South America. It was suggested, for instance, that the Brazil Current (BC) would strengthen (weaken) and the North Brazil Current (NBC) would weaken (strengthen) during slowdown (speed-up) events of the AMOC. This anti-phase pattern was claimed to be a necessary response to the decreased North Atlantic heat piracy during periods of weak AMOC. However, the thermal evolution of the western South Atlantic and the adjacent continent is largely unknown and a compelling record of the BC-NBC anti-phase behavior remains elusive. Here we address this issue, presenting high temporal resolution SST and MAT records from the BC and southeastern South America, respectively. We identify a warming in the western South Atlantic during Heinrich Stadial 1 (HS1), which is followed first by a drop and then by increasing temperatures during the Bølling-Allerød, in-phase with an existing NBC record. Additionally, a similar SST evolution is shown by a southernmost eastern South Atlantic record, suggesting a South Atlantic-wide pattern in SST evolution during most of Termination 1. Over southeastern South America, our MAT record shows a two-step increase during Termination 1, synchronous with atmospheric CO2 rise (i.e., during the second half of HS1 and during the Younger Dryas), and lagging abrupt SST changes by several thousand years. This delay corroborates the notion that the long duration of HS1 was fundamental to drive the Earth out of the last glacial.

Comprehensive metabolic profiling of chronic low-grade inflammation among generally healthy individuals.

PubMed

Pietzner, Maik; Kaul, Anne; Henning, Ann-Kristin; Kastenmüller, Gabi; Artati, Anna; Lerch, Markus M; Adamski, Jerzy; Nauck, Matthias; Friedrich, Nele

2017-11-30

Inflammation occurs as an immediate protective response of the immune system to a harmful stimulus, whether locally confined or systemic. In contrast, a persisting, i.e., chronic, inflammatory state, even at a low-grade, is a well-known risk factor in the development of common diseases like diabetes or atherosclerosis. In clinical practice, laboratory markers like high-sensitivity C-reactive protein (hsCRP), white blood cell count (WBC), and fibrinogen, are used to reveal inflammatory processes. In order to gain a deeper insight regarding inflammation-related changes in metabolism, the present study assessed the metabolic patterns associated with alterations in inflammatory markers. Based on mass spectrometry and nuclear magnetic resonance spectroscopy we determined a comprehensive panel of 613 plasma and 587 urine metabolites among 925 apparently healthy individuals. Associations between inflammatory markers, namely hsCRP, WBC, and fibrinogen, and metabolite levels were tested by linear regression analyses controlling for common confounders. Additionally, we tested for a discriminative signature of an advanced inflammatory state using random forest analysis. HsCRP, WBC, and fibrinogen were significantly associated with 71, 20, and 19 plasma and 22, 3, and 16 urine metabolites, respectively. Identified metabolites were related to the bradykinin system, involved in oxidative stress (e.g., glutamine or pipecolate) or linked to the urea cycle (e.g., ornithine or citrulline). In particular, urine 3'-sialyllactose was found as a novel metabolite related to inflammation. Prediction of an advanced inflammatory state based solely on 10 metabolites was well feasible (median AUC: 0.83). Comprehensive metabolic profiling confirmed the far-reaching impact of inflammatory processes on human metabolism. The identified metabolites included not only those already described as immune-modulatory but also completely novel patterns. Moreover, the observed alterations provide molecular links to inflammation-associated diseases like diabetes or cardiovascular disorders.

MRI-negative PET-positive temporal lobe epilepsy: a distinct surgically remediable syndrome.

PubMed

Carne, R P; O'Brien, T J; Kilpatrick, C J; MacGregor, L R; Hicks, R J; Murphy, M A; Bowden, S C; Kaye, A H; Cook, M J

2004-10-01

Most patients with non-lesional temporal lobe epilepsy (NLTLE) will have the findings of hippocampal sclerosis (HS) on a high resolution MRI. However, a significant minority of patients with NLTLE and electroclinically well-lateralized temporal lobe seizures have no evidence of HS on MRI. Many of these patients have concordant hypometabolism on fluorodeoxyglucose-PET ([18F]FDG-PET). The pathophysiological basis of this latter group remains uncertain. We aimed to determine whether NLTLE without HS on MRI represents a variant of or a different clinicopathological syndrome from that of NLTLE with HS on MRI. The clinical, EEG, [18F]FDG-PET, histopathological and surgical outcomes of 30 consecutive NLTLE patients with well-lateralized EEG but without HS on MRI (HS-ve TLE) were compared with 30 consecutive age- and sex-matched NLTLE patients with well-lateralized EEG with HS on MRI (HS+ve TLE). Both the HS+ve TLE group and the HS-ve TLE patients had a high degree of [18F]FDG-PET concordant lateralization (26 out of 30 HS-ve TLE versus 27 out of 27 HS+ve TLE). HS-ve TLE patients had more widespread hypometabolism on [18F]FDG-PET by blinded visual analysis [odds ratio (OR = + infinity (2.51, -), P = 0.001]. The HS-ve TLE group less frequently had a history of febrile convulsions [OR = 0.077 (0.002-0.512), P = 0.002], more commonly had a delta rhythm at ictal onset [OR = 3.67 (0.97-20.47), P = 0.057], and less frequently had histopathological evidence of HS [OR = 0 (0-0.85), P = 0.031]. There was no significant difference in surgical outcome despite half of those without HS having a hippocampal-sparing procedure. Based on the findings outlined, HS-ve PET-positive TLE may be a surgically remediable syndrome distinct from HS+ve TLE, with a pathophysiological basis that primarily involves lateral temporal neocortical rather than mesial temporal structures.

Influence of gantry rotation time and scan mode on image quality in ultra-high-resolution CT system.

PubMed

Honda, Osamu; Yanagawa, Masahiro; Hata, Akinori; Kikuchi, Noriko; Miyata, Tomo; Tsukagoshi, Shinsuke; Uranishi, Ayumi; Tomiyama, Noriyuki

2018-06-01

To investigate the image quality of helical scan (HS) mode and non-helical scan (non-HS) mode on ultra-high-resolution CT in different gantry rotation time. non-HS with 0.35 s/rot (non-HS200 mA/0.35 s). Three observers compared each non-HS image with HS image, and scored non-HS images by using 3-point scale, paying attention to normal findings, abnormal findings, noise, streak artifact, and overall image quality. Statistical analysis was performed with Steel-Dwass test. Overall image quality (score: 2.45) and noise (score: 2.42) of non-HS 200 mA/1.5s was statistically best (p < 0.0005). Overall Image quality and noise of non-HS200 mA/0.75 s (score: 2.0) was comparable to that of HS200 mA/1.5 s. CTDIvol of HS200 mA/1.5 s is 23.2 mGy. CTDIvol of non-HS200 mA/1.5 s, non-HS200 mA/0.75 s, non-HS200 mA/0.35 s is 19.2 mGy, 9.8 mGy, 4.7 mGy. Overall image quality and noise of non-helical scan is better than that of helical scan in the same rotation time. Overall Image quality of non-HS200 mA/0.75 s is comparable to that of HS200 mA/1.5 s, though the radiation dose of non-HS200 mA/0.75 s is lower than that of HS200 mA/1.5 s. Copyright © 2018 Elsevier B.V. All rights reserved.

Influence of 7 days of hindlimb suspension and intermittent weight support on rat muscle mechanical properties

NASA Technical Reports Server (NTRS)

Pierotti, David J.; Roy, Roland R.; Flores, Vinicio; Edgerton, Reggie

1990-01-01

The effect of intermittent periods of weight support on a decrease in mass of the soleus (Sol) and medial gastrocnemius (MG) muscles atrophied by hindlimb suspension (HS) was investigated in rats subjected to continuous HS for seven days or an HS plus intermittent (10 min every 6 hrs of slow walking on a treadmill) weight support (HS-WS). After 7 d HS, the Sol weight relative to body weight was 21 and 9 percent lower in Hs and HS-WS, respectively, than in control rats. Maximum tetanic tension/muscle mass ratio was significantly lower in HS than in controls; the HS-WS rats had values similar to controls, whereas the maximum tetanic tension/muscle weight was significantly elevated in HS-WS compared to controls. Contraction times were 25 percent faster in the Sol and unchanged in the MG of HS rats, indicating that a low-force short-duration exercise regime results in a significant functional recovery in the 'slow' Sol, whereas the 'fast' MG is less affected.

Minimal 2'-O-methyl phosphorothioate linkage modification pattern of synthetic guide RNAs for increased stability and efficient CRISPR-Cas9 gene editing avoiding cellular toxicity

PubMed Central

Basila, Megan; Kelley, Melissa L.

2017-01-01

Since its initial application in mammalian cells, CRISPR-Cas9 has rapidly become a preferred method for genome engineering experiments. The Cas9 nuclease is targeted to genomic DNA using guide RNAs (gRNA), either as the native dual RNA system consisting of a DNA-targeting CRISPR RNA (crRNA) and a trans-activating crRNA (tracrRNA), or as a chimeric single guide RNA (sgRNA). Entirely DNA-free CRISPR-Cas9 systems using either Cas9 protein or Cas9 mRNA and chemically synthesized gRNAs allow for transient expression of CRISPR-Cas9 components, thereby reducing the potential for off-targeting, which is a significant advantage in therapeutic applications. In addition, the use of synthetic gRNA allows for the incorporation of chemical modifications for enhanced properties including improved stability. Previous studies have demonstrated the utility of chemically modified gRNAs, but have focused on one pattern with multiple modifications in co-electroporation with Cas9 mRNA or multiple modifications and patterns with Cas9 plasmid lipid co-transfections. Here we present gene editing results using a series of chemically modified synthetic sgRNA molecules and chemically modified crRNA:tracrRNA molecules in both electroporation and lipid transfection assessing indel formation and/or phenotypic gene knockout. We show that while modifications are required for co-electroporation with Cas9 mRNA, some modification patterns of the gRNA are toxic to cells compared to the unmodified gRNA and most modification patterns do not significantly improve gene editing efficiency. We also present modification patterns of the gRNA that can modestly improve Cas9 gene editing efficiency when co-transfected with Cas9 mRNA or Cas9 protein (> 1.5-fold difference). These results indicate that for certain applications, including those relevant to primary cells, the incorporation of some, but not all chemical modification patterns on synthetic crRNA:tracrRNA or sgRNA can be beneficial to CRISPR-Cas9 gene editing. PMID:29176845

Minimal 2'-O-methyl phosphorothioate linkage modification pattern of synthetic guide RNAs for increased stability and efficient CRISPR-Cas9 gene editing avoiding cellular toxicity.

PubMed

Basila, Megan; Kelley, Melissa L; Smith, Anja van Brabant

2017-01-01

Since its initial application in mammalian cells, CRISPR-Cas9 has rapidly become a preferred method for genome engineering experiments. The Cas9 nuclease is targeted to genomic DNA using guide RNAs (gRNA), either as the native dual RNA system consisting of a DNA-targeting CRISPR RNA (crRNA) and a trans-activating crRNA (tracrRNA), or as a chimeric single guide RNA (sgRNA). Entirely DNA-free CRISPR-Cas9 systems using either Cas9 protein or Cas9 mRNA and chemically synthesized gRNAs allow for transient expression of CRISPR-Cas9 components, thereby reducing the potential for off-targeting, which is a significant advantage in therapeutic applications. In addition, the use of synthetic gRNA allows for the incorporation of chemical modifications for enhanced properties including improved stability. Previous studies have demonstrated the utility of chemically modified gRNAs, but have focused on one pattern with multiple modifications in co-electroporation with Cas9 mRNA or multiple modifications and patterns with Cas9 plasmid lipid co-transfections. Here we present gene editing results using a series of chemically modified synthetic sgRNA molecules and chemically modified crRNA:tracrRNA molecules in both electroporation and lipid transfection assessing indel formation and/or phenotypic gene knockout. We show that while modifications are required for co-electroporation with Cas9 mRNA, some modification patterns of the gRNA are toxic to cells compared to the unmodified gRNA and most modification patterns do not significantly improve gene editing efficiency. We also present modification patterns of the gRNA that can modestly improve Cas9 gene editing efficiency when co-transfected with Cas9 mRNA or Cas9 protein (> 1.5-fold difference). These results indicate that for certain applications, including those relevant to primary cells, the incorporation of some, but not all chemical modification patterns on synthetic crRNA:tracrRNA or sgRNA can be beneficial to CRISPR-Cas9 gene editing.

Active tactile sampling by an insect in a step-climbing paradigm

PubMed Central

Krause, André F.; Dürr, Volker

2012-01-01

Many insects actively explore their near-range environment with their antennae. Stick insects (Carausius morosus) rhythmically move their antennae during walking and respond to antennal touch by repetitive tactile sampling of the object. Despite its relevance for spatial orientation, neither the spatial sampling patterns nor the kinematics of antennation behavior in insects are understood. Here we investigate unrestrained bilateral sampling movements during climbing of steps. The main objectives are: (1) How does the antennal contact pattern relate to particular object features? (2) How are the antennal joints coordinated during bilateral tactile sampling? We conducted motion capture experiments on freely climbing insects, using steps of different height. Tactile sampling was analyzed at the level of antennal joint angles. Moreover, we analyzed contact patterns on the surfaces of both the obstacle and the antenna itself. Before the first contact, both antennae move in a broad, mostly elliptical exploratory pattern. After touching the obstacle, the pattern switches to a narrower and faster movement, caused by higher cycle frequencies and lower cycle amplitudes in all joints. Contact events were divided into wall- and edge-contacts. Wall contacts occurred mostly with the distal third of the flagellum, which is flexible, whereas edge contacts often occurred proximally, where the flagellum is stiff. The movement of both antennae was found to be coordinated, exhibiting bilateral coupling of functionally analogous joints [e.g., left head-scape (HS) joint with right scape-pedicel (SP) joint] throughout tactile sampling. In comparison, bilateral coupling between homologous joints (e.g., both HS joints) was significantly weaker. Moreover, inter-joint coupling was significantly weaker during the contact episode than before. In summary, stick insects show contact-induced changes in frequency, amplitude and inter-joint coordination during tactile sampling of climbed obstacles. PMID:22754513

Selective determination of semi-volatile thiophene compounds in water by molecularly imprinted polymer thin films with direct headspace gas chromatography sulfur chemiluminescence detection.

PubMed

Hijazi, Hassan Y; Bottaro, Christina S

2018-02-26

Water-compatible molecularly imprinted polymer (MIP) thin films are coupled with headspace gas chromatography sulfur chemiluminescence detection (HS-GC-SCD) to create a new approach for the determination of trace concentrations of thiophene compounds in water samples. Thiophene compounds are persistent, typically petrogenic, organic pollutants of concern due to their potential for biomagnification and bioaccumulation, mutagenicity, and carcinogenicity in terrestrial and aquatic fauna. Identification and quantitation in water, particularly following oil spills, is a priority. Following adsorption of the thiophenes to the MIPs, the MIP-bound analytes are analyzed directly by HS-GC-SCD, with minimal sample manipulation and virtually no organic solvent. Calibration curves of spiked seawater were linear from 5 μg L -1 to 100 μg L -1 and limits of detection (LOD) were in the range of 0.24-0.82 μg L -1 . Low matrix effects were observed in the analysis of thiophene compounds in seawater making the method suitable for use in fresh and saline waters without modification. Acceptable reproducibility was obtained for analysis of thiophene compounds from spiked seawater samples at RSDs ≤7.0% (n = 3).

Influence of surface charge, binding site residues and glycosylation on Thielavia terrestris cutinase biochemical characteristics

PubMed Central

Shirke, Abhijit N.; Basore, Danielle; Holton, Samantha; Su, An; Baugh, Evan; Butterfoss, Glenn L.; Makhatadze, George

2016-01-01

Cutinases are esterases of industrial importance for applications in recycling and surface modification of polyesters. The cutinase from Thielavia terrestris (TtC) is distinct in terms of its ability to retain its stability and activity in acidic pH. Stability and activity in acidic pHs are desirable for esterases as the pH of the reaction tends to go down with the generation of acid. The pH stability and activity are governed by the charged state of the residues involved in catalysis or in substrate binding. In this study, we performed the detailed structural and biochemical characterization of TtC coupled with surface charge analysis to understand its acidic tolerance. The stability of TtC in acidic pH was rationalized by evaluating the contribution of charge interactions to the Gibbs free energy of unfolding at varying pHs. The activity of TtC was found to be limited by substrate binding affinity, which is a function of the surface charge. Additionally, the presence of glycosylation affects the biochemical characteristics of TtC owing to steric interactions with residues involved in substrate binding. PMID:26758295

Surface modification of titanium substrates with silver nanoparticles embedded sulfhydrylated chitosan/gelatin polyelectrolyte multilayer films for antibacterial application.

PubMed

Li, Wen; Xu, Dawei; Hu, Yan; Cai, Kaiyong; Lin, Yingcheng

2014-06-01

To develop Ti implants with potent antibacterial activity, a novel "sandwich-type" structure of sulfhydrylated chitosan (Chi-SH)/gelatin (Gel) polyelectrolyte multilayer films embedding silver (Ag) nanoparticles was coated onto titanium substrate using a spin-assisted layer-by-layer assembly technique. Ag ions would be enriched in the polyelectrolyte multilayer films via the specific interactions between Ag ions and -HS groups in Chi-HS, thus leading to the formation of Ag nanoparticles in situ by photo-catalytic reaction (ultraviolet irradiation). Contact angle measurement and field emission scanning electron microscopy equipped with energy dispersive X-ray spectroscopy were employed to monitor the construction of Ag-containing multilayer on titanium surface, respectively. The functional multilayered films on titanium substrate [Ti/PEI/(Gel/Chi-SH/Ag) n /Gel] could efficiently inhibit the growth and activity of Bacillus subtitles and Escherichia coli onto titanium surface. Moreover, studies in vitro confirmed that Ti substrates coating with functional multilayer films remained the biological functions of osteoblasts, which was reflected by cell morphology, cell viability and ALP activity measurements. This study provides a simple, versatile and generalized methodology to design functional titanium implants with good cyto-compatibility and antibacterial activity for potential clinical applications.

Design and Synthesis of 1-(3-(dimethylamino)propyl)-1-(4-fluorophenyl)-1,3-dihydroisobenzofuran-5-carbonitrile (Citalopram) Analogues as Novel Probes for the Serotonin Transporter S1 and S2 Binding Sites

PubMed Central

Banala, Ashwini K.; Zhang, Peng; Plenge, Per; Cyriac, George; Kopajtic, Theresa; Katz, Jonathan L.; Loland, Claus Juul; Newman, Amy Hauck

2013-01-01

The serotonin transporter (SERT) is the primary target for antidepressant drugs. The existence of a high affinity primary orthosteric binding site (S1) and a low affinity secondary site (S2) has been described and their relation to antidepressant pharmacology has been debated. Herein, structural modifications to the N-, 4, 5, and 4’-positions of (±)citalopram (1) are reported. All of the analogues were SERT-selective and demonstrated that steric bulk was tolerated at the SERT S1 site, including two dimeric ligands (15 and 51.) In addition, 8 analogues were identified with similar potencies to S-1 for decreasing the dissociation of [3H]S-1 from the S1 site, via allosteric modulation at S2. Both dimeric compounds had similar affinities for the SERT S1 site (Ki=19.7 and 30.2 nM, respectively), whereas only the N-substituted analogue, 51, was as effective as S-1 in allosterically modulating the binding of [3H]S-1 via S2. PMID:24237160

The neurobiology of self-face recognition in depressed adolescents with low or high suicidality.

PubMed

Quevedo, Karina; Ng, Rowena; Scott, Hannah; Martin, Jodi; Smyda, Garry; Keener, Matt; Oppenheimer, Caroline W

2016-11-01

This study sought to test whether the neurobiology of self-processing differentiated depressed adolescents with high suicidality (HS) from those with low suicidality (LS) and healthy controls (HC; N = 119, MAGE = 14.79, SD = 1.64, Min = 11.3, Max = 17.8). Participants completed a visual self-recognition task in the scanner during which they identified their own or an unfamiliar adolescent face across 3 emotional expressions (happy, neutral or sad). A 3-group (HS, LS, HC) by 2 within-subject factors (2 Self conditions [self, other] and 3 Emotions [happy, neutral, sad]) GLM yielded (a) a main effect of Self condition with all participants showing higher activity in the right occipital, precuneus and fusiform during the self- versus other-face conditions; (b) a main effect of Group where all depressed youth showed higher dorsolateral prefrontal cortex activity than HC across all conditions, and with HS showing higher cuneus and occipital activity versus both LS and HC; and (c) a Group by Self by Emotion interaction with HS showing lower activity in both mid parietal, limbic, and prefrontal areas in the Happy self versus other-face condition relative to the LS group, who in turn had less activity compared to HC youth. Covarying for depression severity replicated all results except the third finding; In this subsequent analysis, a Group by Self interaction showed that although HC had similar midline cortical structure (MCS) activity for all faces, LS showed higher MCS activity for the self versus other faces, whereas HS showed the opposite pattern. Results suggest that the neurophysiology of emotionally charged self-referential information can distinguish depressed, suicidal youth versus nonsuicidal depressed and healthy adolescents. Neurophysiological differences and implications for the prediction of suicidality in youth are discussed. (PsycINFO Database Record (c) 2016 APA, all rights reserved).

Obesity can predict and promote systemic inflammation in healthy adults.

PubMed

Ellulu, Mohammed S; Khaza'ai, Huzwah; Rahmat, Asmah; Patimah, Ismail; Abed, Yehia

2016-07-15

To find out the differences on biomedical data between obese and non-obese participants, and to identify risk factors associated with systemic inflammation in healthy Palestinian adults. A cross-sectional study involved 105 apparently healthy adults. Interview questionnaire was used to collect personal information. Participants were excluded if they suffered from acute or chronic inflammatory diseases, or continued using medicines, which might affect the biomedical results. In association with increased Body Mass Index (BMI), the obese group displayed significant higher markers including: interleukin 6 (IL-6), high sensitivity C reactive protein (hs-CRP), total cholesterol (TC), systolic blood pressure (SBP), and diastolic blood pressure (DBP). Obese group in association with increased waist circumference (WC) was higher significantly in inflammatory markers (IL-6, hs-CRP), lipid profile (TC) and triglyceride (TG), and blood pressure (SBP, DBP). A tertile of a feature of systemic inflammation (hs-CRP) was created, by Ordinal Logistic Regression, after adjusting for the age, gender, smoking habits, physical activity pattern, father and mother's health history; risk factors were the increased BMI [OR: 1.24] (95% CI: 1.005-1.548, P=0.050), IL-6 [OR: 3.35] (95% CI: 1.341-8.398, P=0.010), DBP [OR: 1.19] (95% CI: 1.034-1.367, P=0.015), and reduced Adiponectin [OR: 0.59] (95% CI: 0.435-0.820, P=0.001). Finally, BMI correlated with IL-6 and hs-CRP (r=0.326, P=0.005; r=0.347, P<0.001; respectively), and hs-CRP correlated with IL-6 (r=0.303, P=0.010), and inversely with Adiponectin (r=-0.342, P=0.001). The increased level of IL-6 and reduced Adiponectin, which strongly associated with obesity, indicated that having high BMI is a useful marker in association with IL-6 and further developed systemic inflammation. Copyright © 2016 Elsevier Ireland Ltd. All rights reserved.

E-cigarette Use Among High School and Middle School Adolescents in Connecticut

PubMed Central

Morean, Meghan E.; Camenga, Deepa R.; Cavallo, Dana A.; Kong, Grace

2015-01-01

Introduction: There is limited evidence on electronic cigarette (e-cigarette) use among U.S. adolescents. Methods: Cross-sectional, anonymous surveys conducted in 4 high schools (HS; n = 3,614) and 2 middle schools (MS; n = 1,166) in Connecticut in November 2013 examined e-cigarette awareness, use patterns, susceptibility to future use, preferences, product components used (battery type, nicotine content, flavors), and sources of marketing and access. Results: High rates of awareness (MS: 84.3%; HS: 92.0%) and of lifetime (3.5% MS, 25.2 % HS) and current (1.5% MS, 12% HS) use of e-cigarettes was observed. Among those who had not tried e-cigarettes, 26.4% of MS and 31.7% of HS students reported being susceptible to future use. Males (OR = 1.70, p < .01), older students (OR = 1.39, p < .05), Caucasians (OR = 2.01, p < .001), ever cigarette smokers (OR = 13.04, p < .001), and current cigarette smokers (OR = 65.11, p < .001) were more likely to be lifetime e-cigarette users and to report greater future susceptibility (males: OR = 1.30; Caucasians: OR = 1.14; ever cigarette smokers; OR = 3.85; current cigarette smokers; OR = 9.81; ps < .01–.001). Among MS students who were lifetime e-cigarette users, 51.2% reported that e-cigarette was the first tobacco product they had tried. E-cigarettes that were rechargeable and had sweet flavors were most popular. Smokers preferred e-cigarettes to cigarettes. Current cigarette smokers were more likely to initiate with nicotine-containing e-cigarettes, and ever and never cigarette smokers to initiate with e-cigarettes without nicotine. Primary sources for e-cigarette advertisements were televisions and gas stations and, for acquiring e-cigarettes, were peers. Conclusions: Longitudinal monitoring of e-cigarette use among adolescents and establishment of policies to limit access are imperatively needed. PMID:25385873

Weak hydrological sensitivity to temperature change over land, independent of climate forcing

NASA Astrophysics Data System (ADS)

Samset, Bjorn H.

2017-04-01

As the global surface temperature changes, so will patterns and rates of precipitation. Theoretically, these changes can be understood in terms of changes to the energy balance of the atmosphere, caused by introducing drivers of climate change such as greenhouse gases, aerosols and altered insolation. Climate models, however, disagree strongly in their prediction of precipitation changes, both for historical and future emission pathways, and per degree of surface warming in idealized experiments. The latter value, often termed the apparent hydrological sensitivity, has also been found to differ substantially between climate drivers. Here, we present the global and regional hydrological sensitivity (HS) to surface temperature changes, for perturbations to CO2, CH4, sulfate and black carbon concentrations, and solar irradiance. Based on results from 10 climate models participating in the Precipitation Driver and Response Model Intercomparison Project (PDRMIP), we show how modeled global mean precipitation increases by 2-3 % per kelvin of global mean surface warming, independent of driver, when the effects of rapid adjustments are removed. Previously reported differences in response between drivers are therefore mainly ascribable to rapid atmospheric adjustment processes. All models show a sharp contrast in behavior over land and over ocean, with a strong surface temperature driven (slow) ocean HS of 3-5 %/K, while the slow land HS is only 0-2 %/K. Separating the response into convective and large-scale cloud processes, we find larger inter-model differences, in particular over land regions. Large-scale precipitation changes are most relevant at high latitudes, while the equatorial HS is dominated by convective precipitation changes. Black carbon stands out as the driver with the largest inter-model slow HS variability, and also the strongest contrast between a weak land and strong sea response. Convective precipitation in the Arctic and large scale precipitation around the Equator are found to be topics where further model investigations and observational constraints may provide rapid improvements to modelling of the precipitation response to future, CO2 dominated climate change.

From the Cover: Fenretinide, Troglitazone, and Elmiron Add to Weight of Evidence Support for Hemangiosarcoma Mode-of-Action From Studies in Mice.

PubMed

Cook, Jon C; Obert, Leslie A; Koza-Taylor, Petra; Coskran, Timothy M; Opsahl, Alan C; Ziemek, Daniel; Roy, Marc; Qian, Jessie; Lawton, Michael P; Criswell, Kay A

2018-01-01

Pharmaceuticals and chemicals produce hemangiosarcomas (HS) in mice, often by nongenotoxic, proliferative mechanisms. A mode-of-action (MOA) for hemangiosarcoma was proposed based on information presented at an international workshop (Cohen et al., Hemangiosarcoma in rodents: Mode-of-action evaluation and human relevance. Toxicol. Sci. 111, 4-18.). Five key elements of the MOA were articulated and included hypoxia, macrophage activation, increased angiogenic growth factors, dysregulated angiogenesis/erythropoiesis, and endothial cell proliferation. The goal of the current study was to add to the weight-of-evidence for the proposed MOA by assessing these key elements with 3 different compounds of varying potency for HS induction: fenretinide (high), troglitazone (intermediate), and elmiron (low). Multiple endpoints, including hypoxia (hyproxyprobe, transcriptomics), endothelial cell (EC) proliferation, and clinical and anatomic pathology, were assessed after 2, 4, and 13-weeks of treatment in B6C3F1 mice. All 3 compounds demonstrated strong evidence for dysregulated erythropoiesis (decrease in RBC and a failure to increase reticulocytes) and macrophage activation (4- to 11-fold increases); this pattern of hematological changes in mice might serve as an early biomarker to evaluate EC proliferation in suspected target organs for potential HS formation. Fenretinide demonstrated all 5 key elements, while troglitazone demonstrated 4 and elmiron demonstrated 3. Transcriptomics provided support for the 5 elements of the MOA, but was not any more sensitive than hypoxyprobe immunohistochemistry for detecting hypoxia. The overall transcriptional evidence for the key elements of the proposed MOA was also consistent with the potency of HS induction. These data, coupled with the previous work with 2-butoxyethanol and pregablin, increase the weight-of-evidence for the proposed MOA for HS formation. © The Author 2017. Published by Oxford University Press on behalf of the Society of Toxicology. All rights reserved. For Permissions, please e-mail: journals.permissions@oup.com.

Obstructive sleep apnea: no independent association to troponins.

PubMed

Hall, Trygve Sørdahl; Herrscher, Tobias; Jarolim, Petr; Fagerland, Morten W; Jensen, Torstein; Hallén, Jonas; Agewall, Stefan; Atar, Dan

2014-05-01

Cardiac troponins (cTn) are to date the most sensitive and specific biochemical markers of myocardial injury. Abnormal breathing patterns in patients with obstructive sleep apnea (OSA) may cause myocardial cell stress detectable by novel cTn assays. The objectives of this study were to investigate whether a new single-molecule cTnI (S-cTnI) assay and a commercially available high-sensitivity cTnT (hs-cTnT) assay would detect myocyte injury in individuals evaluated for possible OSA, and to explore their relation to variables of disordered breathing during sleep. Consecutive individuals referred to Lovisenberg Diakonale Hospital's sleep laboratory between 1 October 2009 and 1 March 2010 were included. We measured cTn in specimens collected the morning after sleep and studied these in relation to variables recorded during polygraphy or polysomnography. All 222 (100 %) individuals had measurable cTn levels using either assay. Stratified into categories according to the apnea-hypopnea index (AHI), patients with OSA (AHI ≥5) had a different distribution of S-cTnI (P = 0.036) and hs-cTnT (P = 0.002) compared to those without (AHI <5). The median (quartiles 1-3) were 3.0 (1.9-6.0) versus 2.3 (1.6-3.8) ng/l for S-cTnI, and 7.0 (5.5-8.7) versus 6.2 (4.9-7.2) ng/l for hs-cTnT. However, in multiple median regression analyses adjusted for conventional predictors, neither S-cTnI (P = 0.57) nor hs-cTnT (P = 0.80) were significantly associated with AHI. This study reveals no association independent of conventional predictors between OSA and myocardial cell injury measured by S-cTnI and hs-cTnT assays. Our findings support a search for novel biomarkers for prognostication of OSA.

High School PREP: Thematic Planning, Fall '83. Preparation for Raising Educational Performance. [HS PREP Experimental Program].

ERIC Educational Resources Information Center

New York City Board of Education, Brooklyn, NY. Div. of Curriculum and Instruction.

This is a handbook designed for carrying out the goals and objectives of Preparation for Raising Educational Performance (PREP), a thematic, remedial program for ninth graders in New York City public schools. The lessons presented in the handbook model an approach to learning which follows the patterns of actual language development: listening,…

HS 0139+0559, HS 0229+8016, HS 0506+7725, and HS 0642+5049: four new long-period cataclysmic variables

NASA Astrophysics Data System (ADS)

Aungwerojwit, A.; Gänsicke, B. T.; Rodríguez-Gil, P.; Hagen, H.-J.; Harlaftis, E. T.; Papadimitriou, C.; Lehto, H.; Araujo-Betancor, S.; Heber, U.; Fried, R. E.; Engels, D.; Katajainen, S.

2005-12-01

We present time-resolved optical spectroscopy and photometry of four relatively bright (V˜14.0-15.5) long-period cataclysmic variables (CVs) discovered in the Hamburg Quasar Survey: HS 0139+0559, HS 0229+8016, HS 0506+7725, and HS 0642+5049. Their respective orbital periods, 243.69±0.49 min, 232.550±0.049 min, 212.7±0.2 min, and 225.90±0.23 min are determined from radial velocity and photometric variability studies. HS 0506+7725 is characterised by strong Balmer and He emission lines, short-period (~10-20 min) flickering, and weak X-ray emission in the ROSAT All Sky Survey. The detection of a deep low state (B≃18.5) identifies HS 0506+7725 as a member of the VY Scl stars. HS 0139+0559, HS 0229+8016, and HS 0642+5049 display thick-disc like spectra and no or only weak flickering activity. HS 0139+0559 and HS 0229+8016 exhibit clean quasi-sinusoidal radial velocity variations of their emission lines but no or very little orbital photometric variability. In contrast, we detect no radial velocity variation in HS 0642+5049 but a noticeable orbital brightness variation. We identify all three systems either as UX UMa-type novalike variables or as Z Cam-type dwarf novae. Our identification of these four new systems underlines that the currently known sample of CVs is rather incomplete even for bright objects. The four new systems add to the clustering of orbital periods in the 3-4 h range found in the sample of HQS selected CVs, and we discuss the large incidence of magnetic CVs and VY Scl/SW Sex stars found in this period range among the known population of CVs.

Analysis of chromatin structure of rat alpha1-acid glycoprotein gene; changes in DNase I hypersensitive sites after thyroid hormone, glucocorticoid hormone and turpentine oil treatment.

PubMed Central

Matsukawa, T; Kawasaki, H; Tanaka, M; Ohba, Y

1997-01-01

Transcription of the ratalpha1-acid glycoprotein (AGP) gene is activated by glucocorticoid, thyroid hormone (T3) and cytokines. Following these treatments, the chromatin structure of this gene was analyzed by means of digestion with DNase I or micrococcal nuclease. Four DNase I hypersensitive sites were observed in the 5'-upstream region of the rat AGP gene of liver cells. They were designated HS1, HS2, HS3 and HS4 (3'-->5'). After T3treatment the sensitivity of HS1 and HS2 increased and after dexamethasone (Dex) treatment that of all four sites did so. Three new sites appeared after turpentine oil treatment, while the sensitivities of HS3 and HS4 increased. We conclude that transcriptional activation of the gene by T3and Dex have very similar mechanisms, but that at the inflammation stage they become slightly different. The increase in sensitivity at HS1 and HS2 after T3treatment in vivo was successfully reproduced in a cell-free system by in vitro treatment with T3. HS1, HS2 and HS3 were also sensitive for micrococcal nuclease. PMID:9185575

Improving patency of coronary conduits "valveless" veins and/or arterial grafts.

PubMed

Lajos, Thomas Z; Robicsek, Francis; Thubrikar, Mano; Urschel, Harold

2007-01-01

Veins used for coronary artery bypass operation have a well-documented limited long-term patency. Internal thoracic artery (ITA) grafts have shown exceptional "durability." Assumptions were made that other arterial conduits have similar characteristics. The purpose of this article is to compare different conduits long-term patency including saphenous veins to other available arterial conduits: inferior epigastric artery (IE), right gastroepiploic artery (RGEA), and radial artery (RA). Recent studies have shown that radial artery bypasses have lower patency rate than saphenous veins. Flow patterns, physiological flow characteristics are reviewed including native vessel disease and area of myocardium supplied. In the case of venous bypasses, the primary culprit of failure seemed to be the quality of the vein itself and the reverse venous valves in the conduit resulting in: (a) trapping-hypertension, (b) thrombosis, (c) turbulence, (d) intimal damage, (e) mismatching in size. Clinical follow-up of our patients up to 8 to 11 years (average 8.9 years) have proved the superior characteristics of the so-called "good veins." In a retrospective study of 436 patients sequential, valveless veins patency was 88.6% versus 72% of reversed valvular segments (p < 0.01). Patients' survival seemed to be significantly improved if these veins were combined with ITA grafts. Patients' survival with one valveless limb HS + ITA was 78% versus HS + SV 52% (p < or = 0.0017) and HS + ITA versus HS + ITA + SV (p < 0.0057). Selective decision-making of the surgeon at the time of the operation is required to choose the best conduit to be able to perform the best operation with the best long-term result.

Some Immunochemical Properties of Dextransucrase and Invertase from Streptococcus mutans

PubMed Central

Fukui, Kazuhiro; Fukui, Yoshio; Moriyama, Takafumi

1974-01-01

Dextransucrase and invertase of some strains of Streptococcus mutans were examined by immunodiffusion with antisera against enzymes purified from strain HS-6 (Bratthall's serotype a). Both antisera cross-reacted with crude enzyme preparations from the other serotype a (strains HS-1 and AHT) and d organisms (strains KIR, OMZ176, and OMZ65) but not with those from serotype b (strains FA-1 and BHT) or c organisms (strains GS-5, Ingbritt, and NCTC 10449). Based upon the antiserum used, the orders of antigenic similarity of the cross-reacting enzymes to the HS-6 enzymes were HS-6 > HS-1 > AHT = KIR = OMZ176 = OMZ65 for dextransucrase and HS-6 = HS-1 > AHT = KIR = OMZ176 = OMZ65 for invertase. It was found that the enzymes from serotype a organisms were not always antigenically homogeneous, as seen between strains HS-6, HS-1, or AHT for dextransucrase, and between the HS group and strain AHT for invertase. Antiserum against the HS-6 dextransucrase markedly inhibited the heterologous dextransucrases of serotype a organisms with the exception of strain HS-1 and d organisms, with or without the addition of dextran. Images PMID:16558114

Fibroblast Growth Factor-based Signaling through Synthetic Heparan Sulfate Blocks Copolymers Studied Using High Cell Density Three-dimensional Cell Printing*

PubMed Central

Sterner, Eric; Masuko, Sayaka; Li, Guoyun; Li, Lingyun; Green, Dixy E.; Otto, Nigel J.; Xu, Yongmei; DeAngelis, Paul L.; Liu, Jian; Dordick, Jonathan S.; Linhardt, Robert J.

2014-01-01

Four well-defined heparan sulfate (HS) block copolymers containing S-domains (high sulfo group content) placed adjacent to N-domains (low sulfo group content) were chemoenzymatically synthesized and characterized. The domain lengths in these HS block co-polymers were ∼40 saccharide units. Microtiter 96-well and three-dimensional cell-based microarray assays utilizing murine immortalized bone marrow (BaF3) cells were developed to evaluate the activity of these HS block co-polymers. Each recombinant BaF3 cell line expresses only a single type of fibroblast growth factor receptor (FGFR) but produces neither HS nor fibroblast growth factors (FGFs). In the presence of different FGFs, BaF3 cell proliferation showed clear differences for the four HS block co-polymers examined. These data were used to examine the two proposed signaling models, the symmetric FGF2-HS2-FGFR2 ternary complex model and the asymmetric FGF2-HS1-FGFR2 ternary complex model. In the symmetric FGF2-HS2-FGFR2 model, two acidic HS chains bind in a basic canyon located on the top face of the FGF2-FGFR2 protein complex. In this model the S-domains at the non-reducing ends of the two HS proteoglycan chains are proposed to interact with the FGF2-FGFR2 protein complex. In contrast, in the asymmetric FGF2-HS1-FGFR2 model, a single HS chain interacts with the FGF2-FGFR2 protein complex through a single S-domain that can be located at any position within an HS chain. Our data comparing a series of synthetically prepared HS block copolymers support a preference for the symmetric FGF2-HS2-FGFR2 ternary complex model. PMID:24563485

Calculation of the Internal and External Risk of Stored Ammunition and Explosives by Means of the Computer Model RISKANAL

DTIC Science & Technology

1998-07-01

950.0 140.0 HS8 HS 8 8 5 0 420.0 50.0 HS9 HS 9 9 2 0 190.0 -245.0 HS10 HS 10 10 1 0 10.0 -245.0 HS11 HS 11 11 1 0 -150.0 50.0 RD1 RD 12 13 1000 50...Ceelen 8 DM&P TNO-DO 9 * DM&P TNO-DQ, accountco6rdinator KL 10* TNO-FEL, Bibliotheek 11 /13 Bibliotheek KMA 14* Lid Instituuts Advies Raad PML Prof. B...Vastgesteld door Maj. Wt. Ceelen Vastgesteld d.d. 9 juni 1998 (deze rubricering wijzigt niet) Titel Ongerubriceerd Managementuittreksel Ongerubriceerd

Diseases associated with hidranitis suppurativa: part 2 of a series on hidradenitis.

PubMed

Scheinfeld, Noah

2013-06-15

Hidradenitis suppurativa (HS), a pathologic follicular disease, impacts patients' lives profoundly and usually occurs in isolation. The diseases with the strongest association are obesity, depression, and pain. HS is associated with many diseases including acne conglobata (AC), dissecting cellulitis, pilonidal cysts, and obesity. Pyoderma fistulans sinifica (fox den disease) appears to be the same entity as Hurley Stage 2 of 3 HS. The rate of acne vulgaris in HS patients mirrors unaffected controls. The most common, albeit still uncommon, association is with seronegative, haplotype unlinked arthritis (most importantly B27), in particular spondolyarthritis. Crohn disease and HS occur together at a rate that varies from 0.6% to 38% in retrospective cases series. Ulcerative colitis occurred with HS in 14% of patients in one series. The next most common association is with pyoderma gangrenosum, but this association is likely under-reported. Synovitis-Acne-Pustulosis Hyperostosis-Osteitis (SAPHO) syndrome, which is rare, has more than 10 reports linking it to HS. Nine case reports have linked Dowling-Degos disease (DDD) to HS and two reports related HS to Fox-Fordyce disease (FF), but because both occur in the axilla this might be a mere coincidence. HS is rarely associated with ophthalmic pathology. Specifically, more than 5 reports link it to Keratitis-Ichthyosis-Deafness syndrome (KID); greater than10 cases link it to interstitial keratitis and 2 cases are linked to Behçet's disease. The presence of proteinuria and acute nephritis link HS to the kidney, especially since and reports have documented resolution of HS after renal transplant. Florid steatocystoma multiplex, Sjogren Syndrome, and HS have been linked and their reports likely underestimate their coincidence because all these entities involve occlusion (albeit by different mechanisms). Three reports link HS and amyloid, but both share some common genetic underpinnings and thus the coincidence of these diseases is likely underreported. Pyoderma vegetans has been noted in 2 cases of HS and 4 cases of Inflammatory Bowel Disease (IBD) and is likely a clue to the linkage of the pathology of IBD and HS. Pityriasis rubra pilaris, in particular Type VI related to HIV, has a relationship more commonly with acne conglobata, but with HS also. Single case reports of diseases associated with HS include systemic lupus erythematosus, acromegaly, Down syndrome, Bazex-Dupre´-Christol, and prurtis ani, but these might be coincidences. Pyogenic Arthritis, Pyoderma gangrenosum, and Acne (PAPA Syndrome) and Pyoderma gangrenosum, Acne, and Suppurative Hidradenitis (PASH Syndrome) are pyodermic-arthritic syndromes that are associated with HS. Erythema nodosum and granulomatous lobular mastitis have been reported with HS but the significance of these reports is uncertain. Because of scarring, HS can result in lymphedema including scrotal elephantiasis and verrucous lymphedema. HS is sometimes accompanied by obesity, hypertension, and anemia and can be considered a disease in the spectrum of metabolic syndrome, a skin disease with systemic consequences. HS, like other types of chronic inflammation when long standing in the perianal and perineal areas, can result in squamous cell cancer. A variety of drugs can induce HS. These include lithium, sirolimus, cyclosporine, vemurafenib, and oral contraceptives. Inverse psoriasis or psoriasis vulgaris as a side effect of infliximab therapy may be associated with HS. These associations aside, most cases of HS occur in isolation without coincident morbidity.

Transport of H2S and HS(-) across the human red blood cell membrane: rapid H2S diffusion and AE1-mediated Cl(-)/HS(-) exchange.

PubMed

Jennings, Michael L

2013-11-01

The rates of H2S and HS(-) transport across the human erythrocyte membrane were estimated by measuring rates of dissipation of pH gradients in media containing 250 μM H2S/HS(-). Net acid efflux is caused by H2S/HS(-) acting analogously to CO2/HCO3(-) in the Jacobs-Stewart cycle. The steps are as follows: 1) H2S efflux through the lipid bilayer and/or a gas channel, 2) extracellular H2S deprotonation, 3) HS(-) influx in exchange for Cl(-), catalyzed by the anion exchange protein AE1, and 4) intracellular HS(-) protonation. Net acid transport by the Cl(-)/HS(-)/H2S cycle is more efficient than by the Cl(-)/HCO3(-)/CO2 cycle because of the rapid H2S-HS(-) interconversion in cells and medium. The rates of acid transport were analyzed by solving the mass flow equations for the cycle to produce estimates of the HS(-) and H2S transport rates. The data indicate that HS(-) is a very good substrate for AE1; the Cl(-)/HS(-) exchange rate is about one-third as rapid as Cl(-)/HCO3(-) exchange. The H2S permeability coefficient must also be high (>10(-2) cm/s, half time <0.003 s) to account for the pH equilibration data. The results imply that H2S and HS(-) enter erythrocytes very rapidly in the microcirculation of H2S-producing tissues, thereby acting as a sink for H2S and lowering the local extracellular concentration, and the fact that HS(-) is a substrate for a Cl(-)/HCO3(-) exchanger indicates that some effects of exogenous H2S/HS(-) may not result from a regulatory role of H2S but, rather, from net acid flux by H2S and HS(-) transport in a Jacobs-Stewart cycle.

Improving Self-Regulation for Obesity Prevention in Head Start: A Randomized Controlled Trial.

PubMed

Lumeng, Julie C; Miller, Alison L; Horodynski, Mildred A; Brophy-Herb, Holly E; Contreras, Dawn; Lee, Hannah; Sturza, Julie; Kaciroti, Niko; Peterson, Karen E

2017-05-01

To determine the effect of an intervention to improve emotional and behavioral self-regulation in combination with an obesity-prevention program on the prevalence of obesity and obesity-related behaviors in preschoolers. This was a cluster-randomized intervention trial in Head Start (HS) classrooms conducted in each of 4 academic years from 2011 to 2015. Participants (697 children; 49% boys; mean age: 4.1 ± 0.5 years; 48% white, 30% African American, 12% Hispanic) were randomly assigned by classroom to 1 of 3 intervention arms: (1) HS + Preschool Obesity Prevention Series (POPS) + Incredible Years Series (IYS) (HS enhanced by the POPS [program targeting evidence-based obesity-prevention behaviors] and the IYS [program to improve children's self-regulation]), (2) HS+POPS, or (3) HS. Primary outcomes were changes in prevalence of obesity, overweight/obesity, BMI z score, and teacher-reported child emotional and behavioral self-regulation; secondary outcomes were dietary intake, outdoor play, screen time, and parent nutrition knowledge and nutrition self-efficacy. HS+POPS+IYS improved teacher-reported self-regulation compared with HS+POPS ( P < .001) and HS ( P < .001), but there was no effect on the prevalence of obesity (16.4% preintervention to 14.3% postintervention in HS+POPS+IYS versus 17.3% to 14.4% in HS+POPS [ P = .54] versus 12.2% to 13.0% in HS [ P = .33]). There was no effect of HS+POPS compared with HS alone ( P = .16). There was no effect on other outcomes except for sugar-sweetened beverage intake (HS+POPS+IYS resulted in a greater decline than HS; P = .005). An intervention for parents and children to improve HS preschoolers' emotional and behavioral self-regulation in combination with an obesity-prevention curriculum did not reduce obesity prevalence or most obesity-related behaviors. Copyright © 2017 by the American Academy of Pediatrics.

A cluster-randomized controlled knowledge translation feasibility study in Alberta community pharmacies using the PARiHS framework: study protocol.

PubMed

Rosenthal, Meagen M; Tsuyuki, Ross T; Houle, Sherilyn Kd

2015-01-01

Despite evidence of benefit for pharmacist involvement in chronic disease management, the provision of these services in community pharmacy has been suboptimal. The Promoting Action on Research Implementation in Health Services (PARiHS) framework suggests that for knowledge translation to be effective, there must be evidence of benefit, a context conducive to implementation, and facilitation to support uptake. We hypothesize that while the evidence and context components of this framework are satisfied, that uptake into practice has been insufficient because of a lack of facilitation. This protocol describes the rationale and methods of a feasibility study to test a facilitated pharmacy practice intervention based on the PARiHS framework, to assist community pharmacists in increasing the number of formal and documented medication management services completed for patients with diabetes, dyslipidemia, and hypertension. A cluster-randomized before-after design will compare ten pharmacies from within a single organization, with the unit of randomization being the pharmacy. Pharmacies will be randomized to facilitated intervention based on the PARiHS framework or usual practice. The Alberta Context Tool will be used to establish the context of practice in each pharmacy. Pharmacies randomized to the intervention will receive task-focused facilitation from an external facilitator, with the goal of developing alternative team processes to allow the greater provision of medication management services for patients with diabetes, hypertension, and dyslipidemia. The primary outcome will be a process evaluation of the needs of community pharmacies to provide more clinical services, the acceptability and uptake of modifications made, and the willingness of pharmacies to participate. Secondary outcomes will include the change in the number of formal and documented medication management services in the aforementioned chronic conditions provided 6 months before, versus after, the intervention between the two groups, and identification of feasible quantitative outcomes for evaluating the effect of the intervention on patient care outcomes. To date, the study has identified and enrolled the ten pharmacies required and initiated the intervention process. This study will be the first to examine the role of facilitation in pharmacy practice, with the goal of scalable and sustainable practice change. Clinicaltrials.gov identifier NCT02191111.

Differential correlations between changes to glutathione redox state, protein ubiquitination, and stress-inducible HSPA chaperone expression after different types of oxidative stress.

PubMed

Girard, Pierre-Marie; Peynot, Nathalie; Lelièvre, Jean-Marc

2018-05-12

In primary bovine fibroblasts with an hspa1b/luciferase transgene, we examined the intensity of heat-shock response (HSR) following four types of oxidative stress or heat stress (HS), and its putative relationship with changes to different cell parameters, including reactive oxygen species (ROS), the redox status of the key molecules glutathione (GSH), NADP(H) NAD(H), and the post-translational protein modifications carbonylation, S-glutathionylation, and ubiquitination. We determined the sub-lethal condition generating the maximal luciferase activity and inducible HSPA protein level for treatments with hydrogen peroxide (H 2 O 2 ), UVA-induced oxygen photo-activation, the superoxide-generating agent menadione (MN), and diamide (DA), an electrophilic and sulfhydryl reagent. The level of HSR induced by oxidative stress was the highest after DA and MN, followed by UVA and H 2 O 2 treatments, and was not correlated to the level of ROS production nor to the extent of protein S-glutathionylation or carbonylation observed immediately after stress. We found a correlation following oxidative treatments between HSR and the level of GSH/GSSG immediately after stress, and the increase in protein ubiquitination during the recovery period. Conversely, HS treatment, which led to the highest HSR level, did not generate ROS nor modified or depended on GSH redox state. Furthermore, the level of protein ubiquitination was maximum immediately after HS and lower than after MN and DA treatments thereafter. In these cells, heat-induced HSR was therefore clearly different from oxidative stress-induced HSR, in which conversely early redox changes of the major cellular thiol predicted the level of HSR and polyubiquinated proteins.

High Prevalence of Echocardiographic Abnormalities among HIV-infected Persons in the Era of Highly Active Antiretroviral Therapy.

PubMed

Mondy, Kristin E; Gottdiener, John; Overton, E Turner; Henry, Keith; Bush, Tim; Conley, Lois; Hammer, John; Carpenter, Charles C; Kojic, Erna; Patel, Pragna; Brooks, John T

2011-02-01

in the era of highly active antiretroviral therapy (HAART), human immunodeficiency virus (HIV)-infected persons have higher cardiovascular disease risk. Little is known about asymptomatic abnormalities in cardiac structure and function in this population. the Study to Understand the Natural History of HIV/AIDS in the Era of Effective Therapy (SUN Study) is a prospective, observational, multi-site cohort of 656 HIV-infected participants who underwent baseline echocardiography during 2004-2006. We examined prevalence of and factors associated with left ventricular systolic dysfunction (LVSD), diastolic dysfunction (DD), pulmonary hypertension (PHTN), left ventricular hypertrophy (LVH), and left atrial enlargement (LAE). participant characteristics were as follows: median age, 41 years; 24% women; 29% non-Hispanic black; 73% receiving HAART; and median CD4+ cell count, 462 cells/μL. Among evaluable participants, 18% had LVSD, 26% had DD, 57% had PHTN (right ventricular pressure >30 mm Hg), 6.5% had LVH, and 40% had LAE. In multivariate analyses, significant factors (P < .05) associated with LVSD were history of MI, elevated highly sensitive C-reactive protein (hsCRP) level, and current tobacco smoking; for DD, elevated hsCRP level and hypertension; for PHTN, current use of ritonavir; for LVH, hypertension, diabetes, non-white race, female sex with elevated body mass index, calculated as the weight in kilograms divided by the square of height in meters, of ≥ 25, elevated hsCRP level, and current use of abacavir; for LAE, hypertension and recent marijuana use. in this large contemporary HIV cohort, the prevalence of subclinical functional and structural cardiac abnormalities was greater than expected for age. Abnormalities were mostly associated with expected and often modifiable risks. Lifestyle modification should become a greater priority in the management of chronic HIV disease.

Structural effects of protein aging: Terminal marking by deamidation in human triosephosphate isomerase

DOE PAGES

Torres-Larios, Alfredo; Enríquez-Flores, Sergio; Méndez, Sara -Teresa; ...

2015-04-17

Deamidation, the loss of the ammonium group of asparagine and glutamine to form aspartic and glutamic acid, is one of the most commonly occurring post-translational modifications in proteins. Since deamidation rates are encoded in the protein structure, it has been proposed that they can serve as molecular clocks for the timing of biological processes such as protein turnover, development and aging. Despite the importance of this process, there is a lack of detailed structural information explaining the effects of deamidation on the structure of proteins. Here, we studied the effects of deamidation on human triosephosphate isomerase (HsTIM), an enzyme formore » which deamidation of N15 and N71 has been long recognized as the signal for terminal marking of the protein. Deamidation was mimicked by site directed mutagenesis; thus, three mutants of HsTIM (N15D, N71D and N15D/N71D) were characterized. The results show that the N71D mutant resembles, structurally and functionally, the wild type enzyme. In contrast, the N15D mutant displays all the detrimental effects related to deamidation. The N15D/N71D mutant shows only minor additional effects when compared with the N15D mutation, supporting that deamidation of N71 induces negligible effects. The crystal structures show that, in contrast to the N71D mutant, where minimal alterations are observed, the N15D mutation forms new interactions that perturb the structure of loop 1 and loop 3, both critical components of the catalytic site and the interface of HsTIM. Based on a phylogenetic analysis of TIM sequences, we propose the conservation of this mechanism for mammalian TIMs.« less

Structural effects of protein aging: Terminal marking by deamidation in human triosephosphate isomerase

DOE Office of Scientific and Technical Information (OSTI.GOV)

Torres-Larios, Alfredo; Enríquez-Flores, Sergio; Méndez, Sara -Teresa

Deamidation, the loss of the ammonium group of asparagine and glutamine to form aspartic and glutamic acid, is one of the most commonly occurring post-translational modifications in proteins. Since deamidation rates are encoded in the protein structure, it has been proposed that they can serve as molecular clocks for the timing of biological processes such as protein turnover, development and aging. Despite the importance of this process, there is a lack of detailed structural information explaining the effects of deamidation on the structure of proteins. Here, we studied the effects of deamidation on human triosephosphate isomerase (HsTIM), an enzyme formore » which deamidation of N15 and N71 has been long recognized as the signal for terminal marking of the protein. Deamidation was mimicked by site directed mutagenesis; thus, three mutants of HsTIM (N15D, N71D and N15D/N71D) were characterized. The results show that the N71D mutant resembles, structurally and functionally, the wild type enzyme. In contrast, the N15D mutant displays all the detrimental effects related to deamidation. The N15D/N71D mutant shows only minor additional effects when compared with the N15D mutation, supporting that deamidation of N71 induces negligible effects. The crystal structures show that, in contrast to the N71D mutant, where minimal alterations are observed, the N15D mutation forms new interactions that perturb the structure of loop 1 and loop 3, both critical components of the catalytic site and the interface of HsTIM. Based on a phylogenetic analysis of TIM sequences, we propose the conservation of this mechanism for mammalian TIMs.« less

Application of headspace solid-phase microextraction (HS-SPME) and comprehensive two-dimensional gas chromatography (GC x GC) for the chemical profiling of volatile oils in complex herbal mixtures.

PubMed

Di, Xin; Shellie, Robert A; Marriott, Philip J; Huie, Carmen W

2004-04-01

The coupling of headspace solid-phase microextraction (HS-SPME) with comprehensive two-dimensional gas chromatography (GC x GC) was shown to be a powerful technique for the rapid sampling and analysis of volatile oils in complex herbal materials. When compared to one-dimensional (1-D) GC, the improved analytical capabilities of GC x GC in terms of increased detection sensitivity and separation power were demonstrated by using HS-SPME/GC x GC for the chemical profiling (fingerprinting) of essential/volatile oils contained in herbal materials of increasing analytical complexity. More than 20 marker compounds belonging to Panax quinquefolius (American ginseng) can be observed within the 2-D contour plots of ginseng itself, a mixture of ginseng and another important herb (P. quinquefolius/Radix angelicae sinensis), as well as a mixture of ginseng and three other herbs (P. quinquefolius /R. angelicae sinensis/R. astragali/R. rehmanniae preparata). Such analytical capabilities should be important towards the authentication and quality control of herbal products, which are receiving increasing attention as alternative medicines worldwide. In particular, the presence of Panax in the herb formulation could be readily identified through its specific peak pattern in the 2-D GC x GC plot.

Temporal profile of inflammatory response to fracture and hemorrhagic shock: Proposal of a novel long-term survival murine multiple trauma model.

PubMed

Kleber, Christian; Becker, Christopher A; Malysch, Tom; Reinhold, Jens M; Tsitsilonis, Serafeim; Duda, Georg N; Schmidt-Bleek, Katharina; Schaser, Klaus D

2015-07-01

Hemorrhagic shock (hS) interacts with the posttraumatic immune response and fracture healing in multiple trauma. Due to the lack of a long-term survival multiple trauma animal models, no standardized analysis of fracture healing referring the impact of multiple trauma on fracture healing was performed. We propose a new long-term survival (21 days) murine multiple trauma model combining hS (microsurgical cannulation of carotid artery, withdrawl of blood and continuously blood pressure measurement), femoral (osteotomy/external fixation) and tibial fracture (3-point bending technique/antegrade nail). The posttraumatic immune response was measured via IL-6, sIL-6R ELISA. The hS was investigated via macrohemodynamics, blood gas analysis, wet-dry lung ration and histologic analysis of the shock organs. We proposed a new murine long-term survival (21 days) multiple trauma model mimicking clinical relevant injury patterns and previously published human posttraumatic immune response. Based on blood gas analysis and histologic analysis of shock organs we characterized and standardized our murine multiple trauma model. Furthermore, we revealed hemorrhagic shock as a causative factor that triggers sIL-6R formation underscoring the fundamental pathophysiologic role of the transsignaling mechanism in multiple trauma. © 2015 Orthopaedic Research Society. Published by Wiley Periodicals, Inc.

Prevalence of Hippocampal Sclerosis in a Clinicopathologically Characterized Cohort.

PubMed

Malek-Ahmadi, Michael; Kahlon, Vickram; Adler, Charles H; Obradov, Aleksandra; Thind, Kabir; Shill, Holly A; Sue, Lucia I; Caviness, John N; Jacobson, Sandra; Sabbagh, Marwan N

2013-01-01

Hippocampal sclerosis (HS) is a neuropathological finding that frequently occurs with pathologies, such as Alzheimer's disease (AD). Prevalence estimates of HS in autopsy-confirmed dementia samples have varied between 0.4% and 24.5%. However, the prevalence of HS within other pathologic groups has not been well characterized. Utilizing a sample of 910 prospectively followed and clinicopathologically confirmed dementia cases, we determined the prevalence of HS among the sample and within specific pathologic groups. HS prevalence of the sample was compared to reported HS prevalence rates in other autopsy-confirmed dementia samples. The age range of the sample was 43 to 106 years, with a mean of 81.49±8.45. Of the 910 cases, 505 were male and 405 were female. For the entire sample, the average educational level was 14.59±2.65years. Of the 910 individuals, 47 (5.16%) cases had HS pathology present at autopsy. Among the 561 AD cases, 26 (4.43%) had HS pathology present. The frontotemporal dementia (FTD)/Pick's group had the highest percentage of cases with HS pathology (23.08%) followed by primary progressive aphasia (PPA) (16.67%) and Parkinson's disease with dementia (PDD) (5.34%). The HS prevalence rate of this study was not significantly different from all but 2 studies. The prevalence of HS pathology in this sample of autopsy-confirmed dementia cases was similar to other reported HS prevalence rates. This study is the first to report the presence of HS pathology in PDD cases.

Speech Understanding Research

DTIC Science & Technology

1976-10-01

HS-II has used word templates of a linguistically simple form (patterned after those developed for PARRY by Cnlby ~ see Colby et al., 1974; see...interesting as an indication of whether or not the potential parallelism can be effectively utilized (see Fennell and Lesser, 1975). On the other...Symposium on Speech Recognition. Carnegie-Mellon University, Pittsburgh, Pennsylvania, 15-19 April 1974. IEEE, New York, 1974, 250-254. (b) Fennell

Effect of protein solution components in the adsorption of Herbaspirillum seropedicae GlnB protein on mica.

PubMed

Ferreira, Cecília F G; Benelli, Elaine M; Klein, Jorge J; Schreiner, Wido; Camargo, Paulo C

2009-10-15

The adsorption of proteins and its buffer solution on mica surfaces was investigated by atomic force microscopy (AFM). Different salt concentration of the Herbaspirillum seropedicae GlnB protein (GlnB-Hs) solution deposited on mica was investigated. This protein is a globular, soluble homotrimer (36kDa), member of PII-like proteins family involved in signal transducing in prokaryote. Supramolecular structures were formed when this protein was deposited onto bare mica surface. The topographic AFM images of the GlnB-Hs films showed that at high salt concentration the supramolecular structures are spherical-like, instead of the typical doughnut-like shape for low salt concentration. AFM images of NaCl and Tris from the buffer solution showed structures with the same pattern as those observed for high salt protein solution, misleading the image interpretation. XPS experiments showed that GlnB protein film covers the mica surface without chemical reaction.

Passive Heating Attenuates Post-exercise Cardiac Autonomic Recovery in Healthy Young Males

PubMed Central

Peçanha, Tiago; Forjaz, Cláudia L. de Moraes; Low, David A.

2017-01-01

Post-exercise heart rate (HR) recovery (HRR) presents a biphasic pattern, which is mediated by parasympathetic reactivation and sympathetic withdrawal. Several mechanisms regulate these post-exercise autonomic responses and thermoregulation has been proposed to play an important role. The aim of this study was to test the effects of heat stress on HRR and HR variability (HRV) after aerobic exercise in healthy subjects. Twelve healthy males (25 ± 1 years, 23.8 ± 0.5 kg/m2) performed 14 min of moderate-intensity cycling exercise (40–60% HRreserve) followed by 5 min of loadless active recovery in two conditions: heat stress (HS) and normothermia (NT). In HS, subjects dressed in a whole-body water-perfused tube-lined suit to increase internal temperature (Tc) by ~1°C. In NT, subjects did not wear the suit. HR, core and skin temperatures (Tc and Tsk), mean arterial pressure (MAP) skin blood flow (SKBF), and cutaneous vascular conductance (CVC) were measured throughout and analyzed during post-exercise recovery. HRR was assessed through calculations of HR decay after 60 and 300 s of recovery (HRR60s and HRR300s), and the short- and long-term time constants of HRR (T30 and HRRt). Post-exercise HRV was examined via calculations of RMSSD (root mean square of successive RR intervals) and RMS (root mean square residual of RR intervals). The HS protocol promoted significant thermal stress and hemodynamic adjustments during the recovery (HS-NT differences: Tc = +0.7 ± 0.3°C; Tsk = +3.2 ± 1.5°C; MAP = −12 ± 14 mmHg; SKBF = +90 ± 80 a.u; CVC = +1.5 ± 1.3 a.u./mmHg). HRR and post-exercise HRV were significantly delayed in HS (e.g., HRR60s = 27 ± 9 vs. 44 ± 12 bpm, P < 0.01; HRR300s = 39 ± 12 vs. 59 ± 16 bpm, P < 0.01). The effects of heat stress (e.g., the HS-NT differences) on HRR were associated with its effects on thermal and hemodynamic responses. In conclusion, heat stress delays HRR, and this effect seems to be mediated by an attenuated parasympathetic reactivation and sympathetic withdrawal after exercise. In addition, the impact of heat stress on HRR is related to the magnitude of the heat stress-induced thermal stress and hemodynamic changes. PMID:29311799

Attenuation of salt-induced hypertension by aqueous calyx extract of Hibiscus sabdariffa.

PubMed

Mojiminiyi, F B O; Audu, Z; Etuk, E U; Ajagbonna, O P

2012-12-18

The aqueous calyx extract of Hibiscus sabdariffa (HS) has a folk reputation as an antihypertensive agent. On account of its antioxidant properties and probably high K+ concentration, we hypothesized that HS may attenuate the development of salt-induced hypertension. Sprague-Dawley rats (n=8 each) were treated for 12 weeks as follows: control (normal diet + water), salt-loaded (8% salt diet + water), HS (normal diet + 6 mg/ml HS), salt+HS (8% salt diet + 6 mg/ml HS) and furosemide (normal diet+ 0.25mg/Kg furosemide). Their blood pressure and heart rates were measured and responses to noradrenalin and acetylcholine (0.01 mg/kg respectively) were estimated. The cationic concentration of 6 mg/ml HS was determined. The Na+ and K+ concentrations of 6 mg/ml HS were 3.6 and 840 mmol/l respectively. The mean arterial pressure (MAP±SEM; mmHg) of salt loaded rats (184.6±29.8) was significantly higher than control (113.2±3.0; P<0.05), HS (90.0±7.4; P<0.001) salt+HS (119.4±8.9; P<0.05) and furosemide (94.9±11.5; P<0.01). The MAP of salt+HS and control rats did not differ significantly and the effect of HS was comparable to furosemide. The pressor response to noradrenalin or vasodilator response to acetylcholine remained similar in all groups. These results suggest that HS attenuated the development of salt-induced hypertension and this attenuation may be associated with its high K+ content or high potassium: sodium ratio and not with altered pressor/depressor response to noradrenalin or acetylcholine. Also the effects of HS and furosemide on blood pressure are comparable.

Resuscitative therapy with erythropoietin reduces oxidative stress and inflammatory responses of vital organs in a rat severe fixed-volume hemorrhagic shock model.

PubMed

Ranjbaran, Mina; Kadkhodaee, Mehri; Seifi, Behjat; Mirzaei, Reza; Ahghari, Parisa

2018-01-01

Hemorrhagic shock (HS) still has a high mortality rate and none of the known resuscitative regimens completely reverse its adverse outcomes. This study investigated the effects of different models of resuscitative therapy on the healing of organ damage in a HS model. Male Wistar rats were randomized into six groups: Sham, without HS induction; HS, without resuscitation; HS+Blood, resuscitation with the shed blood; HS+Blood+NS, resuscitation with blood and normal saline; HS+Blood+RL, resuscitation with blood and Ringer's lactate; EPO, erythropoietin was added to the blood and RL. Blood and urine samples were obtained 3 h after resuscitation. Kidney, liver and brain tissue samples were harvested for multiple organ failure evaluation. Survival rate was the highest in the Sham, EPO and HS+Blood+RL groups compared to others. Plasma creatinine concentration, ALT, AST, urinary NAG activity and renal NGAL mRNA expression significantly increased in the HS+Blood+RL group compared to the Sham group. There was a significant increase in tissue oxidative stress markers and pro-inflammatory cytokines in HS+Blood+RL group compared to the Sham rats. EPO had more protective effects on multiple organ failure compared to the HS+Blood+RL group. EPO, as a resuscitative treatment, attenuated HS-induced organ damage. It seems that it has a potential to be attractive for clinical trials.

Dietary enzymatically treated Artemisia annua L. supplementation alleviates liver oxidative injury of broilers reared under high ambient temperature

NASA Astrophysics Data System (ADS)

Wan, Xiaoli; Zhang, Jingfei; He, Jintian; Bai, Kaiwen; Zhang, Lili; Wang, Tian

2017-09-01

Heat stress induced by high ambient temperature is a major concern in commercial broiler production. To evaluate the effects of dietary enzymatically treated Artemisia annua L. (EA) supplementation on growth performance and liver oxidative injury of broilers reared under heat stress, a total of 320 22-day-old male broilers were randomly allotted into five groups with eight replicates of eight birds each. Broilers in the control group were housed at 22 ± 1 °C and fed the basal diet. Broilers in the HS, HS-EA1, HS-EA2, and HS-EA3 groups were fed basal diet supplemented with 0, 0.75, 1.00, and 1.25 g/kg EA, respectively, and reared under cyclic high temperature (34 ± 1 °C for 8 h/day and 22 ± 1 °C for 16 h/day). Broilers fed EA diets had higher final body weight, average daily body weight gain, and average daily feed intake, as well as liver concentration of reduced glutathione, activities of antioxidant enzymes, abilities to inhibit hydroxyl radical and superoxide radical (HS-EA2 and HS-EA3), and lower liver concentrations of reactive oxygen metabolites, malondialdehyde, and protein carbonyl (HS-EA1, HS-EA2, and HS-EA3) than HS group ( P < 0.05). EA treatment downregulated the mRNA levels of heat shock proteins 70 and 90, upregulated the mRNA levels of nuclear factor erythroid 2-related factor 2 (HS-EA1, HS-EA2, and HS-EA3) and heme oxygenase 1 (HS-EA2 and HS-EA3) in liver of heat-treated broilers ( P < 0.05). In conclusion, EA alleviated heat stress-induced growth depression and liver oxidative injury in broilers, possibly through improving the antioxidant capacity and regulating the pertinent mRNA expression. The appropriate inclusion level of EA in broiler diet is 1.00-1.25 g/kg.

Predictive modelling of fault related fracturing in carbonate damage-zones: analytical and numerical models of field data (Central Apennines, Italy)

NASA Astrophysics Data System (ADS)

Mannino, Irene; Cianfarra, Paola; Salvini, Francesco

2010-05-01

Permeability in carbonates is strongly influenced by the presence of brittle deformation patterns, i.e pressure-solution surfaces, extensional fractures, and faults. Carbonate rocks achieve fracturing both during diagenesis and tectonic processes. Attitude, spatial distribution and connectivity of brittle deformation features rule the secondary permeability of carbonatic rocks and therefore the accumulation and the pathway of deep fluids (ground-water, hydrocarbon). This is particularly true in fault zones, where the damage zone and the fault core show different hydraulic properties from the pristine rock as well as between them. To improve the knowledge of fault architecture and faults hydraulic properties we study the brittle deformation patterns related to fault kinematics in carbonate successions. In particular we focussed on the damage-zone fracturing evolution. Fieldwork was performed in Meso-Cenozoic carbonate units of the Latium-Abruzzi Platform, Central Apennines, Italy. These units represent field analogues of rock reservoir in the Southern Apennines. We combine the study of rock physical characteristics of 22 faults and quantitative analyses of brittle deformation for the same faults, including bedding attitudes, fracturing type, attitudes, and spatial intensity distribution by using the dimension/spacing ratio, namely H/S ratio where H is the dimension of the fracture and S is the spacing between two analogous fractures of the same set. Statistical analyses of structural data (stereonets, contouring and H/S transect) were performed to infer a focussed, general algorithm that describes the expected intensity of fracturing process. The analytical model was fit to field measurements by a Montecarlo-convergent approach. This method proved a useful tool to quantify complex relations with a high number of variables. It creates a large sequence of possible solution parameters and results are compared with field data. For each item an error mean value is computed (RMS), representing the effectiveness of the fit and so the validity of this analysis. Eventually, the method selects the set of parameters that produced the least values. The tested algorithm describes the expected H/S values as a function of the distance from the fault core (D), the clay content (S), and the fault throw (T). The preliminary results of the Montecarlo inversion show that the distance (D) has the most effective influence in the H/S spatial distribution and the H/S value decreases with the distance from the fault-core. The rheological parameter shows a value similar to the diagenetic H/S values (1-1.5). The resulting equation has a reasonable RMS value of 0.116. The results of the Montecarlo models were finally implemented in FRAP, a fault environment modelling software. It is a true 4D tool that can predict stress conditions and permeability architecture associated to a given faults during single or multiple tectonic events. We present some models of fault-related fracturing among the studied faults performed by FRAP and we compare them with the field measurements, to test the validity of our methodology.

Humic supramolecular structures have polar surfaces and unpolar cores in native soil.

PubMed

Fischer, Thomas

2017-09-01

It was the aim of our study to prove the hypothesis that humic substances (HS) in native soil are spatially arranged in descending order of polarity, meaning that highly polar supramolecular subunits shield less polar subunits against the free soil solution and form layers of descending polarity. To address this aim, we consecutively extracted humic substances from soil with 8 M (HS1), 4 M (HS2), 2 M (HS3), 1 M (HS4) and 0.5 M LiCl (HS5) solution in 0.2 M LiOH after Cu 2+ adsorption in batch soil column experiments. Adsorption was performed for 1, 10 and 60 min with concentrations ranging from 9.5 to 110 mg L -1 Cu 2+ in 0.02 M CaCl 2 solution. We assumed that high ionic strength facilitates extraction of most polar organic compounds, with polarity of the extracted HS decreasing with decreasing ionic strength, and that Cu extracted together with the successive HS solely formed coordination complexes, facilitating its use as a tracer for organic matter studies. We hypothesized a delayed Cu adsorption on the less polar fractions in case of spatial shielding due to interception on overlying fractions, and a concurrent Cu adsorption in case of random spatial arrangement. It was concluded that humic substances are shielded against each other in the order of descending polarity of the supramolecular subunits (free soil solution | HS1 | HS2 | HS3 | HS4 | HS5). Copyright © 2017 Elsevier Ltd. All rights reserved.

Optical sectioning microscopy using two-frame structured illumination and Hilbert-Huang data processing

NASA Astrophysics Data System (ADS)

Trusiak, M.; Patorski, K.; Tkaczyk, T.

2014-12-01

We propose a fast, simple and experimentally robust method for reconstructing background-rejected optically-sectioned microscopic images using two-shot structured illumination approach. Innovative data demodulation technique requires two grid-illumination images mutually phase shifted by π (half a grid period) but precise phase displacement value is not critical. Upon subtraction of the two frames the input pattern with increased grid modulation is computed. The proposed demodulation procedure comprises: (1) two-dimensional data processing based on the enhanced, fast empirical mode decomposition (EFEMD) method for the object spatial frequency selection (noise reduction and bias term removal), and (2) calculating high contrast optically-sectioned image using the two-dimensional spiral Hilbert transform (HS). The proposed algorithm effectiveness is compared with the results obtained for the same input data using conventional structured-illumination (SIM) and HiLo microscopy methods. The input data were collected for studying highly scattering tissue samples in reflectance mode. In comparison with the conventional three-frame SIM technique we need one frame less and no stringent requirement on the exact phase-shift between recorded frames is imposed. The HiLo algorithm outcome is strongly dependent on the set of parameters chosen manually by the operator (cut-off frequencies for low-pass and high-pass filtering and η parameter value for optically-sectioned image reconstruction) whereas the proposed method is parameter-free. Moreover very short processing time required to efficiently demodulate the input pattern predestines proposed method for real-time in-vivo studies. Current implementation completes full processing in 0.25s using medium class PC (Inter i7 2,1 GHz processor and 8 GB RAM). Simple modification employed to extract only first two BIMFs with fixed filter window size results in reducing the computing time to 0.11s (8 frames/s).

Abiotic association of PAEs with humic substances and its influence on the fate of PAEs in landfill leachate.

PubMed

Xiaoli, Chai; Rong, Ji; Jun, Wu; Huanhuan, Tong; Youcai, Zhao

2010-03-01

An equilibrium dialysis combined with a (14)C-labeling method was used to study the abiotic association of phthalic acid esters (PAEs) with dissolved humic substances (HS) and its influence on the fate of PAEs in landfill leachate. Elemental analysis and FTIR spectral analysis were carried out on the humic acid (HA) and fulvic acid (FA) components of HS to examine the relationship between the structure of HS and the intensity of the association of the PAEs with HS (K(A)). The results show that the association intensity of HS with PAEs depends greatly on both the properties of the PAEs and the source of HS. The HS have a strong association reaction with dibutyl phthalic acid, which might explain the higher concentration of dibutyl phthalic acid detected in landfill leachate. The pH value strongly affects the K(A) of HS, and it decreases radically when the pH increase from 3.0 to 9.0. The non-specific hydrophobic interaction between HS and PAEs plays a more important role in the abiotic association of HS with PAEs. Elemental analysis and FTIR spectra suggest that the high K(A) values are related to the high aromatic content and larger molecular weight of HS. Copyright (c) 2010 Elsevier Ltd. All rights reserved.

Interleukin-6 treatment reverses apoptosis and blunts susceptibility to intraperitoneal bacterial challenge following hemorrhagic shock.

PubMed

Arikan, Ayse Akcan; Yu, Bi; Mastrangelo, Mary-Ann; Tweardy, David J

2006-03-01

Resuscitation from hemorrhagic shock (HS) predisposes to subsequent infections. Susceptibility to infection following sepsis has been attributed to apoptosis. Interleukin (IL)-6 has been shown to have antiapoptotic properties and to decrease postresuscitation inflammation in rodent and porcine models of HS. The objective was to determine if HS increases host susceptibility to infection, if IL-6 administration at resuscitation reduces this susceptibility, and if changes in susceptibility to infection are accompanied by parallel changes in apoptosis. Mice were randomized into three groups-HS, sham, and no-surgery control-and each group was further randomized to receive either IL-6 (3 microg/kg; HS/IL-6) or placebo (HS/P) at the start of resuscitation. In the HS-infection protocol, each mouse was challenged intraperitoneally the next day with a sublethal dose of Staphylococcus aureus (4x107 colony-forming units); 24 hrs later, the peritoneal cavity was lavaged and the major organs were harvested for culture. In the HS-apoptosis protocol, the livers were harvested the next day and analyzed by means of the terminal deoxynucleotidyl transferase dUTP-biotin nick-end-labeling (TUNEL) assay. HS/P mice had a six- to eight-fold increase in total bacterial counts in comparison with sham and control mice that was attributable to a seven- to nine-fold increase in liver burden. IL-6 treatment reduced total and liver bacterial counts in HS/IL-6 mice by 62% and 69%, respectively, to levels statistically indistinguishable from IL-6-treated sham and control mice. The number of TUNEL-positive liver cells in the HS/P group was increased eight-fold vs. that in the sham group (p=.002); IL-6 resuscitation completely reversed the HS-induced increase in TUNEL-positive cells in the HS/IL-6 group (p=.002). IL-6 treatment at resuscitation eliminated the HS-mediated increase in total and liver bacterial burden and protected the liver from HS-induced apoptosis. Reduced liver apoptosis may explain the ability of IL-6 to blunt the HS-induced increase in susceptibility to bacterial challenge.

Early diagnosis of myocardial infarction using absolute and relative changes in cardiac troponin concentrations.

PubMed

Irfan, Affan; Reichlin, Tobias; Twerenbold, Raphael; Meister, Marc; Moehring, Berit; Wildi, Karin; Bassetti, Stefano; Zellweger, Christa; Gimenez, Maria Rubini; Hoeller, Rebeca; Murray, Karsten; Sou, Seoung Mann; Mueller, Mira; Mosimann, Tamina; Reiter, Miriam; Haaf, Philip; Ziller, Ronny; Freidank, Heike; Osswald, Stefan; Mueller, Christian

2013-09-01

Absolute changes in high-sensitivity cardiac troponin T (hs-cTnT) seem to have higher diagnostic accuracy in the early diagnosis of acute myocardial infarction compared with relative changes. It is unknown whether the same applies to high-sensitivity cardiac troponin I (hs-cTnI) assays and whether the combination of absolute and relative change might further increase accuracy. In a prospective, international multicenter study, high-sensitivity cardiac troponin (hs-cTn) was measured with 3 novel assays (hs-cTnT, Roche Diagnostics Corp, Indianapolis, Ind; hs-cTnI, Beckman Coulter Inc, Brea, Calif; hs-cTnI, Siemens, Munich, Germany) in a blinded fashion at presentation and after 1 and 2 hours in a blinded fashion in 830 unselected patients with suspected acute myocardial infarction. The final diagnosis was adjudicated by 2 independent cardiologists. The area under the receiver operating characteristic curve for diagnosing acute myocardial infarction was significantly higher for 1- and 2-hour absolute versus relative hs-cTn changes for all 3 assays (P < .001). The area under the receiver operating characteristic curve of the combination of 2-hour absolute and relative change (hs-cTnT 0.98 [95% confidence interval {CI}, 0.97-0.99]; hs-cTnI, Beckman Coulter Inc, 0.97 [95% CI, 0.96-0.99]; hs-cTnI, Siemens, 0.96 [95% CI, 0.93-0.99]) were high and provided some benefit compared with the use of absolute change alone for hs-cTnT, but not for the hs-cTnI assays. Reclassification analysis confirmed the superiority of absolute changes versus relative changes. Absolute changes seem to be the preferred metrics for both hs-cTnT and hs-cTnI in the early diagnosis of acute myocardial infarction. The combination of absolute and relative changes provides a small added value for hs-cTnT, but not for hs-cTnI. Copyright © 2013 Elsevier Inc. All rights reserved.

Deep-sea ostracode species diversity: Response to late Quaternary climate change

USGS Publications Warehouse

Cronin, T. M.; DeMartino, D.M.; Dwyer, Gary S.; Rodriguez-Lazaro, J.

1999-01-01

Late Quaternary ostracode assemblages from the North Atlantic Ocean were studied to establish the effect of climatic changes of the past 210,000 yr (marine oxygen isotope stages 7–1) on deep-sea benthic biodiversity and faunal composition. Two-hundred and twenty five samples from the Chain 82-24 Core 4PC (41°43′N, 32°51′W, 3427 m water depth) on the western Mid-Atlantic Ridge revealed high amplitude fluctuations in ostracode abundance and diversity coincident with orbital and suborbital scale climate oscillations measured by several paleoceanographic proxy records. During the past 210,000 yr, ostracode biodiversity as measured by species number (S) and the Shannon–Weaver index, H(S), oscillated from H(S)=0.4 during glacial periods (marine isotope stages 6, 5d, 5b, 4, and 2) to H(S)=1.1 during interglacial and interstadial periods (stages 7, 5e, 5c, 5a, 3 and 1). A total of 23 diversity peaks could be recognized. Eleven of these signify major periods of high diversity [H(S)>0.8, S = 10–21] occurring every 15–20 ka. Twelve were minor peaks which may represent millennial-scale diversity oscillations. The composition of ostracode assemblages varies with Krithe-dominated assemblages characterizing glacial intervals, and Argilloecia–Cytheropteron characterizing deglacials, and trachyleberid genera (Poseidonamicus, Echinocythereis, Henryhowella, Oxycythereis) abundant during interglacials. Diversity and faunal composition changes can be matched to independent deep-sea paleoceanographic tracers such as benthic foraminiferal carbon isotopes, Krithe trace elements (Mg/Ca ratios), and to North Atlantic region climate records such as Greenland ice cores. When interpreted in light of ostracode species' ecology, these faunal and diversity patterns provide evidence that deep-sea benthic ecosystems experience significant reorganization in response to climate changes over orbital to millennial timescales.

Electromyographic and biomechanical analysis of step negotiation in Charcot Marie Tooth subjects whose level walk is not impaired.

PubMed

Lencioni, Tiziana; Piscosquito, Giuseppe; Rabuffetti, Marco; Sipio, Enrica Di; Diverio, Manuela; Moroni, Isabella; Padua, Luca; Pagliano, Emanuela; Schenone, Angelo; Pareyson, Davide; Ferrarin, Maurizio

2018-05-01

Charcot-Marie-Tooth (CMT) is a slowly progressive disease characterized by muscular weakness and wasting with a length-dependent pattern. Mildly affected CMT subjects showed slight alteration of walking compared to healthy subjects (HS). To investigate the biomechanics of step negotiation, a task that requires greater muscle strength and balance control compared to level walking, in CMT subjects without primary locomotor deficits (foot drop and push off deficit) during walking. We collected data (kinematic, kinetic, and surface electromyographic) during walking on level ground and step negotiation, from 98 CMT subjects with mild-to-moderate impairment. Twenty-one CMT subjects (CMT-NLW, normal-like-walkers) were selected for analysis, as they showed values of normalized ROM during swing and produced work at push-off at ankle joint comparable to those of 31 HS. Step negotiation tasks consisted in climbing and descending a two-step stair. Only the first step provided the ground reaction force data. To assess muscle activity, each EMG profile was integrated over 100% of task duration and the activation percentage was computed in four phases that constitute the step negotiation tasks. In both tasks, CMT-NLW showed distal muscle hypoactivation. In addition, during step-ascending CMT-NLW subjects had relevant lower activities of vastus medialis and rectus femoris than HS in weight-acceptance, and, on the opposite, a greater activation as compared to HS in forward-continuance. During step-descending, CMT-NLW showed a reduced activity of tibialis anterior during controlled-lowering phase. Step negotiation revealed adaptive motor strategies related to muscle weakness due to disease in CMT subjects without any clinically apparent locomotor deficit during level walking. In addition, this study provided results useful for tailored rehabilitation of CMT patients. Copyright © 2018 Elsevier B.V. All rights reserved.

A brain-derived neurotrophic factor polymorphism Val66Met identifies fibromyalgia syndrome subgroup with higher body mass index and C-reactive protein.

PubMed

Xiao, Yangming; Russell, I Jon; Liu, Ya-Guang

2012-08-01

A common single nucleotide polymorphism (SNP) in the gene of brain-derived neurotrophic factor (BDNF) results from a substitution at position 66 from valine (Val) to methionine (Met) and may predispose to human neuropsychiatric disorders. We proposed to determine whether these BDNF gene SNPs were associated with fibromyalgia syndrome (FMS) and/or any of its typical phenotypes. Patients with FMS (N = 95) and healthy normal controls (HNC, N = 58) were studied. Serum high-sensitivity C-reactive protein (hsCRP) levels were measured using an enzyme-linked immunosorbent assay (ELISA). The BDNF SNPs were determined using polymerase chain reaction-restriction fragment length polymorphism (PCR-RFLP).The BDNF SNP distribution was 65 (68%) Val/Val, 28 (30%) Val/Met, and 2 (2%) Met/Met for FMS and 40 (69%), 17(29%), and 1 (2%) for HNC, respectively. The serum high-sensitivity C-reactive protein (hsCRP)and body mass index (BMI) in FMS were higher than in HNC. The FMS with BDNF Val66Val had significantly higher mean BMI (P = 0.0001) and hsCRP (P = 0.02) than did FMS carrying the Val66Met genotype. This pattern was not found in HNC. Phenotypic measures of subjective pain, pain threshold, depression, or insomnia did not relate to either of the BDNF SNPs in FMS. The relative distribution BDNF SNPs did not differ between FMS and HNC. The BDNF Val66Met polymorphism is not selective for FMS. The BDNF Val66Val SNP identifies a subgroup of FMS with elevated hsCRP and higher BMI. This is the first study to associate a BDNF polymorphism with a FMS subgroup phenotype.

Metabolic responses and "omics" technologies for elucidating the effects of heat stress in dairy cows.

PubMed

Min, Li; Zhao, Shengguo; Tian, He; Zhou, Xu; Zhang, Yangdong; Li, Songli; Yang, Hongjian; Zheng, Nan; Wang, Jiaqi

2017-06-01

Heat stress (HS) negatively affects various industries that rely on animal husbandry, particularly the dairy industry. A better understanding of metabolic responses in HS dairy cows is necessary to elucidate the physiological mechanisms of HS and offer a new perspective for future research. In this paper, we review the current knowledge of responses of body metabolism (lipid, carbohydrate, and protein), endocrine profiles, and bovine mammary epithelial cells during HS. Furthermore, we summarize the metabolomics and proteomics data that have revealed the metabolite profiles and differentially expressed proteins that are a feature of HS in dairy cows. Analysis of metabolic changes and "omics" data demonstrated that HS is characterized by reduced lipolysis, increased glycolysis, and catabolism of amino acids in dairy cows. Here, analysis of the impairment of immune function during HS and of the inflammation that arises after long-term HS might suggest new strategies to ameliorate the effects of HS in dairy production.

A Pediatrician’s Practical Guide to Diagnosing and Treating Hereditary Spherocytosis in Neonates

PubMed Central

Yaish, Hassan M.; Gallagher, Patrick G.

2015-01-01

Newborn infants who have hereditary spherocytosis (HS) can develop anemia and hyperbilirubinemia. Bilirubin-induced neurologic dysfunction is less likely in these neonates if the diagnosis of HS is recognized and appropriate treatment provided. Among neonates listed in the USA Kernicterus Registry, HS was the third most common underlying hemolytic condition after glucose-6-phosphate dehydrogenase deficiency and ABO hemolytic disease. HS is the leading cause of direct antiglobulin test (direct Coombs) negative hemolytic anemia requiring erythrocyte transfusion in the first months of life. We anticipate that as physicians become more familiar with diagnosing HS in the newborn period, fewer neonates with HS will develop hazardous hyperbilirubinemia or present to emergency departments with unanticipated symptomatic anemia. We predict that early suspicion, prompt diagnosis and treatment, and anticipatory guidance will prevent adverse outcomes in neonates with HS. The purpose of this article was to review the neonatal presentation of HS and to provide practical and up-to-date means of diagnosing and treating HS in neonates. PMID:26009624

2-O Heparan Sulfate Sulfation by Hs2st Is Required for Erk/Mapk Signalling Activation at the Mid-Gestational Mouse Telencephalic Midline

PubMed Central

Chan, Wai Kit; Howe, Katherine; Clegg, James M.; Guimond, Scott E.; Price, David J.; Turnbull, Jeremy E.; Pratt, Thomas

2015-01-01

Heparan sulfate (HS) is a linear carbohydrate composed of polymerized uronate-glucosamine disaccharide units that decorates cell surface and secreted glycoproteins in the extracellular matrix. In mammals HS is subjected to differential sulfation by fifteen different heparan sulfotransferase (HST) enzymes of which Hs2st uniquely catalyzes the sulfation of the 2-O position of the uronate in HS. HS sulfation is postulated to be important for regulation of signaling pathways by facilitating the interaction of HS with signaling proteins including those of the Fibroblast Growth Factor (Fgf) family which signal through phosphorylation of extracellular signal-regulated kinases Erk1/2. In the developing mouse telencephalon Fgf2 signaling regulates proliferation and neurogenesis. Loss of Hs2st function phenocopies the thinned cerebral cortex of mutant mice in which Fgf2 or Erk1/2 function are abrogated, suggesting the hypothesis that 2-O-sulfated HS structures play a specific role in Fgf2/Erk signaling pathway in this context in vivo. This study investigated the molecular role of 2-O sulfation in Fgf2/Erk signaling in the developing telencephalic midline midway through mouse embryogenesis at E12.5. We examined the expression of Hs2st, Fgf2, and Erk1/2 activity in wild-type and Hs2st-/- mice. We found that Hs2st is expressed at high levels at the midline correlating with high levels of Erk1/2 activation and Erk1/2 activation was drastically reduced in the Hs2st-/- mutant at the rostral telencephalic midline. We also found that 2-O sulfation is specifically required for the binding of Fgf2 protein to Fgfr1, its major cell-surface receptor at the rostral telencephalic midline. We conclude that 2-O sulfated HS structures generated by Hs2st are needed to form productive signaling complexes between HS, Fgf2 and Fgfr1 that activate Erk1/2 at the midline. Overall, our data suggest the interesting possibility that differential expression of Hs2st targets the rostral telencephalic midline for high levels of Erk signaling by increasing the sensitivity of cells to an Fgf2 signal that is rather more widespread. PMID:26075383

The placido wavefront sensor and preliminary measurement on a mechanical eye.

PubMed

Carvalho, Luis Alberto; Castro, Jarbas C

2006-02-01

The hardware and software of a novel wavefront sensor was developed (The sensor presented here is patent pending.). It has the same principal of the Hartmann-Shack (HS) and other sensors that are based on slope information for recovery of wavefront surface, but a different symmetry, and does not use individual microlenses. This polar symmetry might offer differences during practical measurements that may add value to current and well-established "gold standard" techniques. The sensor consists of a set of concentric "half-donut" surfaces (longitudinally sectioned toroids) molded on an acrylic surface with a CCD located at the focal plane. When illuminated with a plane wavefront, it focuses a symmetric pattern of concentric discs on the CCD plane; for a distorted wavefront, a nonsymmetric disc pattern is formed (similar to images of a placido-based videokeratographer). From detection of shift in the radial direction, radial slopes are computed for a maximum of 2880 points, and the traditional least-squares procedure is used to fit these partial derivatives to a set of 15 conventional OSA-VSIA Zernike polynomials. Theoretical computations for several synthetic surfaces containing low-order aberration (LOA) and high-order aberration (HOA) were implemented for both the HS and the new sensor. Root mean square error (RMSE) in microns when theoretical data was taken as control, for HS sensor and new sensor, was 0.02 and 0.00003 for LOA (defocus, astigmatism) and 0.07 and 0.06 for HOA (coma, spherical, and higher terms), respectively. After this, practical preliminary measurements on a mechanical eye with a 5-mm pupil and 10 different defocus aberrations ranging from -5 D to 5 D, in steps of 1 D, were compared between sensors. RMSE for difference in measurements for HS and new sensor for sphere, cylinder, and axis, was 0.13 D, 0.07 D, and 11. Measurements were taken only on defocus aberrations. Qualitative images for astigmatism are shown. Although practical in vivo tests were not conducted in this first study, we also discuss certain possible alignment differences that may arise as a result of the different symmetry of the new sensor. To take any conclusive assumption regarding the accuracy and/or precision of this new sensor, when compared with other well-established sensors, statistically significant in vivo measurements will need to be conducted.

Hindlimb Suspension as a Model to Study Ophthalmic Complications in Microgravity Status Report: Optimization of Rat Retina Flat Mounts Staining to Study Vascular Remodeling

NASA Technical Reports Server (NTRS)

Theriot, Corey A.; Zanello, Susana B.

2014-01-01

Preliminary data from a prior tissue-sharing experiment has suggested that early growth response protein-1 (Egr1), a transcription factor involved in various stress responses in the vasculature, is induced in the rat retina after 14 days of hindlimb suspension (HS) and may be evidence that mechanical stress is occurring secondary to the cephalad fluid shift. This mechanical stress could cause changes in oxygenation of the retina, and the subsequent ischemia- or inflammation-driven hypoxia may lead to microvascular remodeling. This microvascular remodeling process can be studied using image analysis of retinal vessels and can be then be quantified by the VESsel GENeration Analysis (VESGEN) software, a computational tool that quantifies remodeling patterns of branching vascular trees and capillary or vasculogenic networks. Our project investigates whether rodent HS is a valid model to study the effects of simulated-weightlessness on ocular structures and their relationship with intracranial pressure (ICP). One of the hypotheses to be tested is that HS-induced cephalad fluid shift is accompanied by vascular engorgement that produces changes in retinal oxygenation, leading to oxidative stress, hypoxia, microvascular remodeling, and cellular degeneration. We have optimized the procedure to obtain flat mounts of rat retina, staining of the endothelial lining in vasculature and acquisition of high quality images suitable for VESGEN analysis. Briefly, eyes were fixed in 4% paraformaldehyde for 24 hours and retinas were detached and then mounted flat on microscope slides. The microvascular staining was done with endothelial cell-specific isolectin binding, coupled to Alexa-488 fluorophore. Image acquisition at low magnification and high resolution was performed using a new Leica SP8 confocal microscope in a tile pattern across the X,Y plane and multiple sections along the Z-axis. This new confocal microscope has the added capability of dye separation using the Linear Unmixing method and allows us to remove the autofluorescence originating from the photoreceptor layer. In summary, we have an improved method for studying the retinal microvasculature that will provide an increase in the quality of images captured and will be applied throughout the various animal cohorts of the recentlyinitiated study that will evaluate rodent HS as a model to study ophthalmic complications in microgravity.

Hidradenitis Suppurativa Is Associated with Polycystic Ovary Syndrome: A Population-Based Analysis in the United States.

PubMed

Garg, Amit; Neuren, Erica; Strunk, Andrew

2018-06-01

Polycystic ovary syndrome (PCOS) has been linked to hidradenitis suppurativa (HS). However, evidence establishing a relationship between the two conditions is limited. We sought to determine the prevalence of PCOS among patients with HS and the strength of the association. We performed a cross-sectional analysis involving 22,990 patients with HS using clinical data from a multihealth system analytics platform comprising more than 55 million unique patients across all census regions of the United States. The prevalence of PCOS among patients with HS was 9.0%, compared with 2.9% in patients without HS (P < 0.0001). The likelihood of patients with HS having PCOS was 2.14 (95% confidence interval 2.04-2.24) times that of patients without HS, and PCOS was associated with HS across all subgroups. The strength of the HS association with PCOS was similar to that of diabetes mellitus (odds ratio 2.88, 95% confidence interval 2.83-2.93) and obesity (odds ratio 3.93, 95% confidence interval 3.87-3.99) with PCOS. The influence of disease severity on the strength of association with PCOS could not be assessed, nor could an HS phenotype for patients also having PCOS. This analysis could not establish directionality of relationship, nor causal link. In conclusion, PCOS is associated with HS, and patients with HS who have symptoms or signs of androgen excess should be screened for PCOS. Copyright © 2018 The Authors. Published by Elsevier Inc. All rights reserved.

Effect of sleep deprivation on driving safety in housestaff.

PubMed

Marcus, C L; Loughlin, G M

1996-12-01

Sleep deprivation is known to affect driving safety. Housestaff (HS) are routinely sleep-deprived when on call. We hypothesized that this would affect their driving. We therefore administered questionnaires regarding driving to 70 pediatric HS, who were on call every fourth night, and to 85 faculty members (FAC), who were rarely disturbed at night. HS were questioned about events during their residency, and FAC were questioned about events during the preceding three years. There was an 87% response rate for each group. HS slept 2.7 +/- 0.9 (SD) hours when on call vs 7.2 +/- 0.8 hours when not on call (p < 0.001). 44% of HS had fallen asleep when stopped at a light, vs 12.5% FAC (p < 0.001). 23% of HS had fallen asleep while driving vs. 8% FAC (ns). A total of 49% of HS had fallen asleep at the wheel; 90% of these events occurred post-call. In contrast, only 13% of FAC had fallen asleep at the wheel (p < 0.001). HS had received a total of 25 traffic citations for moving violations vs. 15 for FAC and were involved in 20 motor vehicle accidents vs. 11 for FAC. One traffic citation clearly resulted from HS falling asleep at the wheel vs. none for FAC. We conclude that HS frequently fall asleep when driving post-call. We speculate that current HS work schedules may place some HS at risk for injury to themselves and others. Further study, using prospectively objective measures is indicated.

Metabolites of hirsuteine and hirsutine, the major indole alkaloids of Uncaria rhynchophylla, in rats.

PubMed

Nakazawa, Takahiro; Banba, Koh-ichi; Hata, Kazumasa; Nihei, Yutaka; Hoshikawa, Ayumi; Ohsawa, Keisuke

2006-08-01

The metabolic fate of hirsuteine (HT) and hirsutine (HS), the major indole alkaloids of Uncaria rhynchophylla, was investigated using rats. On HPLC analysis, urine from rats orally administered HT were found to contain two metabolites (HT1 and HT2) together with unchanged HT. Similarly HS also was metabolized to two compounds (HS1 and HS2). Metabolite structures were determined to be 11-hydroxyhirsuteine-11-O-beta-D-glucuronide (HT1), 11-hydroxyhirsuteine (HT2), 11-hydroxyhirsutine-11-O-beta-D-glucuronide (HS1) and 11-hydroxyhirsutine (HS2), based on spectroscopic and chemical data. HT1 and HS1 were also detected in bile from rats administered HT and HS, respectively. Total cumulative urinary excretion within 72 h of oral administration was approximately 14% and 26% of the HT and HS doses, respectively, while total cumulative biliary excretion was 35% and 46%, respectively. HT and HS 11-hydroxylation were catalyzed by rat liver microsomes. This 11-hydroxylation activity was inhibited by addition of SKF-525A (a nonselective CYP inhibitor) or cimetidine (a CYP2C inhibitor). These results indicate that orally administered HT and HS are converted to 11-hydroxy metabolites in rats, and that the metabolites are predominantly excreted in bile rather than urine following glucuronidation. Furthermore, the results suggest that CYP2C enzymes are involved, at least in part, in the specific 11-hydroxylation of HT and HS.

Alleviation of chronic heat stress in broilers by dietary supplementation of betaine and turmeric rhizome powder: dynamics of performance, leukocyte profile, humoral immunity, and antioxidant status.

PubMed

Akhavan-Salamat, Hossein; Ghasemi, Hossein Ali

2016-01-01

Heat stress (HS), one of the most serious climate problems of tropical and subtropical countries, negatively affects the production performance of broilers. Keeping this in view, the current study was aimed at elucidating the effects of supplementing betaine (Bet) and dried turmeric rhizome powder (TRP), either singly or in combination, on growth performance, leukocyte profile, humoral immunity, and antioxidant status in broilers kept under chronic HS. A total of 625 one-day-old Ross male chicks were randomly assigned to five treatment groups (5 replicates of 25 birds per replicate pen). From day 1, the birds were either kept at the thermoneutral zone (TN) or exposed to HS (33 ± 1°C) to the conclusion of study, day 42. THeat stress (HS), one of the most serious climate problems of tropical and subtropical countries, negatively affects the production performance of broilers. Keeping this in view, the current study was aimed at elucidating the effects of supplementing betaine (Bet) and dried turmeric rhizome powder (TRP), either singly or in combination, on growth performance, leukocyte profile, humoral immunity, and antioxidant status in broilers kept under chronic HS. A total of 625 one-day-old Ross male chicks were randomly assigned to five treatment groups (5 replicates of 25 birds per replicate pen). From day 1, the birds were either kept at the thermoneutral zone (TN) or exposed to HS (33 ± 1°C) to the conclusion of study, day 42. The treatment groups were as follows: thermoneutral control (TN-CON), HS-CON, HS-Bet, HS-TRP, and HS-BT (fed Bet and TRP). The results showed that decreases in body weight gain, feed intake, and increases in feed-to-gain ratio and mortality induced by HS were partially restored by dietary supplementation of Bet and TRP. The heterophil/lymphocyte ratio, total, and IgG antibody titers against sheep red blood cell for secondary responses in the HS-TRP and HS-BT groups were also similar to those of the broilers in the TN-CON group but better (P < 0.05) than for HS-CON group. An increase (P < 0.05) in serum concentration of malondialdehyde induced by HS was significantly decreased by dietary supplementations. The serum glutathione peroxidase and superoxide dismutase activities were also higher (P < 0.05) in the supplemented groups compared to both TN and HS-CON groups. In conclusion, dietary supplementation of either Bet or TRP alone or in combination can partially ameliorate some of the detrimental effects of HS in broilers. Results also suggest that TRP might be better than Bet for improving stress tolerance and immune response in heat-stressed broilers.he treatment groups were as follows: thermoneutral control (TN-CON), HS-CON, HS-Bet, HS-TRP, and HS-BT (fed Bet and TRP). The results showed that decreases in body weight gain, feed intake, and increases in feed-to-gain ratio and mortality induced by HS were partially restored by dietary supplementation of Bet and TRP. The heterophil/lymphocyte ratio, total, and IgG antibody titers against sheep red blood cell for secondary responses in the HS-TRP and HS-BT groups were also similar to those of the broilers in the TN-CON group but better (P < 0.05) than for HS-CON group. An increase (P < 0.05) in serum concentration of malondialdehyde induced by HS was significantly decreased by dietary supplementations. The serum glutathione peroxidase and superoxide dismutase activities were also higher (P < 0.05) in the supplemented groups compared to both TN and HS-CON groups. In conclusion, dietary supplementation of either Bet or TRP alone or in combination can partially ameliorate some of the detrimental effects of HS in broilers. Results also suggest that TRP might be better than Bet for improving stress tolerance and immune response in heat-stressed broilers.

Heparin octasaccharide decoy liposomes inhibit replication of multiple viruses

PubMed Central

Hendricks, Gabriel L.; Velazquez, Lourdes; Pham, Serena; Qaisar, Natasha; Delaney, James C.; Viswanathan, Karthik; Albers, Leila; Comolli, James C.; Shriver, Zachary; Knipe, David M.; Kurt-Jones, Evelyn A.; Fygenson, Deborah K.; Trevejo, Jose M.

2016-01-01

Heparan sulfate (HS) is a ubiquitous glycosaminoglycan that serves as a cellular attachment site for a number of significant human pathogens, including respiratory syncytial virus (RSV), human parainfluenza virus 3 (hPIV3), and herpes simplex virus (HSV). Decoy receptors can target pathogens by binding to the receptor pocket on viral attachment proteins, acting as ‘molecular sinks’ and preventing the pathogen from binding to susceptible host cells. Decoy receptors functionalized with HS could bind to pathogens and prevent infection, so we generated decoy liposomes displaying HS-octasaccharide (HS-octa). These decoy liposomes significantly inhibited RSV, hPIV3, and HSV infectivity in vitro to a greater degree than the original HS-octa building block. The degree of inhibition correlated with the density of HS-octa displayed on the liposome surface. Decoy liposomes with HS-octa inhibited infection of viruses to a greater extent than either full-length heparin or HS-octa alone. Decoy liposomes were effective when added prior to infection or following the initial infection of cells in vitro. By targeting the well-conserved receptor-binding sites of HS-binding viruses, decoy liposomes functionalized with HS-octa are a promising therapeutic antiviral agent and illustrate the utility of the liposome delivery platform. PMID:25637710

Sorption of selected pharmaceuticals by a river sediment: role and mechanisms of sediment or Aldrich humic substances.

PubMed

Le Guet, Thibaut; Hsini, Ilham; Labanowski, Jérôme; Mondamert, Leslie

2018-05-01

Sorption of pharmaceuticals onto sediments is frequently related to organic matter content. Thus, the present work aimed to compare the effect of humic substances (HS) extracted from a river sediment versus Aldrich (HS) on the sorption of selected pharmaceuticals onto this river sediment. The results exhibited no "unique" effect of the presence of HS from the same origin. Thus, the sediment HS increased the sorption of sulfamethoxazole (SMX), diclofenac (DCF), and trimethoprim (TMP), but reduced the sorption of atenolol (ATN). The presence of Aldrich HS increased the sorption of TMP and ATN and decreased the sorption of SMX and DCF. Fluorescence quenching measurements revealed that these effects cannot be explained only by the presence of pharmaceutical HS associations. The use of several sorption models suggested that the sorption of SMX, DCF, and ATN involves multilayer mechanisms. Furthermore, it was pointed out that the presence of HS does not change the sorption mechanisms although it was observed interaction between HS and the sediment. Indeed, the sediment HS sorbs onto the sediment whereas the Aldrich HS tends to mobilize organic compounds from the sediment to the solution.

Using two-dimensional correlation size exclusion chromatography (2D-CoSEC) to explore the size-dependent heterogeneity of humic substances for copper binding.

PubMed

Lee, Yun-Kyung; Hur, Jin

2017-08-01

Knowledge of the heterogeneous distribution of humic substances (HS) reactivities along a continuum of molecular weight (MW) is crucial for the systems where the HS MW is subject to change. In this study, two dimensional correlation spectroscopy combined with size exclusion chromatography (2D-CoSEC) was first utilized to obtain a continuous and heterogeneous presence of copper binding characteristics within bulk HS with respect to MW. HS solutions with varying copper concentrations were directly injected into a size exclusion chromatography (SEC) system with Tris-HCl buffer as a mobile phase. Several validation tests confirmed neither structural disruption of HS nor competition effect of the mobile phase used. Similar to batch systems, fluorescence quenching was observed in the chromatograms over a wide range of HS MW. 2D-CoSEC maps of a soil-derived HS (Elliot soil humic acid) showed the greater fluorescence quenching degrees with respect to the apparent MW on the order of 12500 Da > 10600 Da > 7000 Da > 15800 Da. The binding constants calculated based on modified Stern-Volmer equation were consistent with the 2D-CoSEC results. More heterogeneity of copper binding affinities within bulk HS was found for the soil-derived HS versus an aquatic HS. The traditional fluorescence quenching titration method using ultrafiltered HS size fractions failed to delineate detailed distribution of the copper binding characteristics, exhibiting a much shorter range of the binding constants than those obtained from the 2D-CoSEC. Our proposed technique demonstrated a great potential to describe metal binding characteristics of HS at high MW resolution, providing a clear picture of the size-dependent metal-HS interactions. Copyright © 2017 Elsevier Ltd. All rights reserved.

The effects of phase III cardiac rehabilitation in serum and salivary Hs-CRP and anthropometric measurements in patients with coronary artery disease.

PubMed

Jamshidpour, Boshra; Moghadam, Behrouz Attarbashi; Vasaghi-Gharamaleki, Behnoosh; Mirzaii-Dizgah, Iraj; Nejatian, Mostafa

2013-09-01

Cardiac rehabilitation is a key part in the treatment of coronary artery disease (CAD) by its anti-infammatory effects. However, the effect of exercise training programs on salivary concentrations of high-sensitivity C-reactive protein (hs-CRP) in patients with coronary artery disease has not been well studied. The objective of this study was to evaluate the effect of phase III cardiac rehabilitation on serum and salivary levels of hs-CRP, in relation to the anthropometric measurements of obesity and the relationship between salivary and serum levels of hs-CRP in CAD male patients. Forty male volunteers (45-75 years) with CAD participated in 6 to 8 weeks of moderate intensity aerobic exercise training consisting of 45 minutes sessions of treadmill, stationary bicycle and arm ergometer. Anthropometric measurements of obesity, serum level of hs-CRP, stimulated and nonstimulated salivary level of hs-CRP were measured at the beginning, in the middle and at the end of exercise sessions. All anthropometric measurements increased (p < 0.05) following cardiac rehabilitation except waist-hip ratio. Serum hs-CRP level reduced by 36% independent to the anthropometric measurements changes. Stimulated and nonstimulated salivary hs-CRP level decreased 68 and 54%, respectively, after 24 sessions of cardiac rehabilitation. Nonstimulated salivary hs-CRP levels correlated to serum levels of hs-CRP at baseline and after 24 sessions (p < 0.05). Phase III cardiac rehabilitation seems to be effective to improve serum and salivary hs-CRP concentrations independent of anthropometric measurements. Nonstimulated salivary hs-CRP measurement could be a surrogate for blood measurement of hs-CRP during cardiac rehabilitation in male patients with CAD.

Contraceptive failure after hysteroscopic sterilization: Analysis of clinical and demographic data from 103 unplanned pregnancies

PubMed Central

Li, Xiang; Jones, Christopher A.; Wood, Samuel H.

2015-01-01

Objective This investigation examined data on unplanned pregnancies following hysteroscopic sterilization (HS). Methods A confidential questionnaire was used to collect data from women with medically confirmed pregnancy (n=103) registered after undergoing HS. Results Mean (±SD) patient age and body mass index (BMI) were 29.5±4.6 years and 27.7±6.1 kg/m2, respectively. Peak pregnancy incidence was reported at 10 months after HS, although <3% of unplanned pregnancies occurred within the first three months following HS. Mean (±SD) interval between HS and pregnancy was 19.6±14.9 (range, 2 to 84) months. Patients age ≥30 years and BMI <25 reported conception after HS somewhat sooner than younger patients, although the differences in time to pregnancy were not significant (P=0.24 and 0.09, respectively). The recommended post-HS hysterosalpingogram (to confirm proper placement and bilateral tubal occlusion) was obtained by 66% (68/103) of respondents. Conclusion This report is the first to provide patient-derived data on contraceptive failures after HS. While adherence to backup contraception 3 months after HS can be poor, many unintended pregnancies with HS occur long after the interval when alternate contraceptive is required. Many patients who obtain HS appear to ignore the manufacturer's guidance regarding the post-procedure hysterosalpingogram to confirm proper device placement, although limited insurance coverage likely contributes to this problem. The greatest number of unplanned pregnancies occurred 10 months after HS, but some unplanned pregnancies were reported up to 7 years later. Age, BMI, or surgical history are unlikely to predict contraceptive failure with HS. Further follow-up studies are planned to capture additional data on this issue. PMID:26623413

Effects of different warming patterns on the translocations of cadmium and copper in a soil-rice seedling system.

PubMed

Ge, Liqiang; Cang, Long; Liu, Hui; Zhou, Dongmei

2015-10-01

Heavy-metal-polluted rice poses potential threats to food security and has received great attention in recent years, while how elevated temperature affects the translocation of heavy metals in soil-rice system is unclear. In this study, potting experiments were conducted in plant growth chambers for 24 days to evaluate the effects of different warming patterns on cadmium (Cd) and copper (Cu) migrations in soil-rice seedling system. Rice seedlings were cultivated under four different day/night temperature patterns: 25/18 °C (CK), 25/23 °C (N5), 30/18 °C (D5), and 30/23 °C (DN5), respectively. Non-contaminated soil (CS), Cd/Cu lightly polluted soil (LS), and highly polluted soil (HS) were chosen for experiments. The results showed that different warming patterns decreased soil pH and elevated available soil Cd/Cu concentrations. The shoot and root biomass were increased by 39.0-320 and 28.6-348 %, respectively. Warming induced significant (p < 0.05) increase of Cd/Cu uptake and translocation in rice seedlings, especially for the Cd concentration in shoot. The Cd concentrations of shoot increased by 5-12 times and up to 8 times for LS and HS, respectively. Meanwhile, the Cd concentration of shoot increased with warming while that of root kept unchanged, indicating that warming promoted cadmium translocation from root to shoot (about -four to nine times of CK), while warming changed the Cu concentration of shoot similarly to that of root and had no significant effects on Cu translocations in rice seedlings. Our study may provide improved understanding for Cd/Cu fates in soil-rice system by warming and imply that heavy metals had the higher environmental risk under the future global warming.

An improved genetic algorithm for designing optimal temporal patterns of neural stimulation

NASA Astrophysics Data System (ADS)

Cassar, Isaac R.; Titus, Nathan D.; Grill, Warren M.

2017-12-01

Objective. Electrical neuromodulation therapies typically apply constant frequency stimulation, but non-regular temporal patterns of stimulation may be more effective and more efficient. However, the design space for temporal patterns is exceedingly large, and model-based optimization is required for pattern design. We designed and implemented a modified genetic algorithm (GA) intended for design optimal temporal patterns of electrical neuromodulation. Approach. We tested and modified standard GA methods for application to designing temporal patterns of neural stimulation. We evaluated each modification individually and all modifications collectively by comparing performance to the standard GA across three test functions and two biophysically-based models of neural stimulation. Main results. The proposed modifications of the GA significantly improved performance across the test functions and performed best when all were used collectively. The standard GA found patterns that outperformed fixed-frequency, clinically-standard patterns in biophysically-based models of neural stimulation, but the modified GA, in many fewer iterations, consistently converged to higher-scoring, non-regular patterns of stimulation. Significance. The proposed improvements to standard GA methodology reduced the number of iterations required for convergence and identified superior solutions.

Clustering methods applied in the detection of Ki67 hot-spots in whole tumor slide images: an efficient way to characterize heterogeneous tissue-based biomarkers.

PubMed

Lopez, Xavier Moles; Debeir, Olivier; Maris, Calliope; Rorive, Sandrine; Roland, Isabelle; Saerens, Marco; Salmon, Isabelle; Decaestecker, Christine

2012-09-01

Whole-slide scanners allow the digitization of an entire histological slide at very high resolution. This new acquisition technique opens a wide range of possibilities for addressing challenging image analysis problems, including the identification of tissue-based biomarkers. In this study, we use whole-slide scanner technology for imaging the proliferating activity patterns in tumor slides based on Ki67 immunohistochemistry. Faced with large images, pathologists require tools that can help them identify tumor regions that exhibit high proliferating activity, called "hot-spots" (HSs). Pathologists need tools that can quantitatively characterize these HS patterns. To respond to this clinical need, the present study investigates various clustering methods with the aim of identifying Ki67 HSs in whole tumor slide images. This task requires a method capable of identifying an unknown number of clusters, which may be highly variable in terms of shape, size, and density. We developed a hybrid clustering method, referred to as Seedlink. Compared to manual HS selections by three pathologists, we show that Seedlink provides an efficient way of detecting Ki67 HSs and improves the agreement among pathologists when identifying HSs. Copyright © 2012 International Society for Advancement of Cytometry.

Male Peer Support to Hostile Sexist Attitudes Influences Rape Proclivity.

PubMed

Durán, Mercedes; Megías, Jesús L; Moya, Miguel

2018-07-01

Sexual assault affects a large proportion of women in the world. Although most rapes are committed by one man, the act itself may be influenced by many (e.g., the peer group). Hostile sexism (HS) has repeatedly been associated with men's rape proclivity, but the influence exerted by the HS of the peer group on rape proclivity has not been investigated. In this study, we explored the impact of perceived male peer support to HS on participants' rape proclivity. A sample of Spanish undergraduate students from a university in the south of Spain ( N = 134) completed the Ambivalent Sexism Inventory. Immediately afterwards, they received feedback on the supposed sexist responses of a peer group (high vs. low in HS); we kept the benevolent sexism (BS) of the peer group at medium levels. Next, we assessed participants' rape proclivity using acquaintance rape scenarios. Results showed an interaction between participants' own levels of HS and information about the HS of the peer group. Men high in HS reported higher rape proclivity in the high-HS peer-group condition than in the low-HS peer-group condition. By contrast, information on the peer group did not affect self-reported rape proclivity of men low in HS. Results also corroborated the relationship between participants' levels of HS and rape proclivity, and expanded the literature by revealing an unexpected influence of participants' BS on rape proclivity.

Cytosolic phosphoenolpyruvate carboxykinase is a response gene involved in porcine adipocyte adaptation to heat stress.

PubMed

Qu, Huan; Ajuwon, Kolapo M

2018-05-04

Heat stress (HS) leads to increased lipid storage and expression of cytosolic phosphoenolpyruvate carboxykinase (PCK1) in pig adipocytes. However, the importance of PCK1 activation and lipid storage in the adaptive response to HS is unknown. Therefore, in vitro experiments were conducted to investigate the effect of PCK1 inhibition with 3-mercaptopicolinic acid (3MPA) on lipid storage and adipocyte response during HS. In vitro culture of adipocytes under HS (41.0 °C) increased (P < 0.05) triacylglycerol accumulation compared with control (37.0 °C). HS increased (P < 0.05) reactive oxygen species level and 3MPA further upregulated (P < 0.05) its level. Heat shock protein 70 (HSP70) gene expression was induced (P < 0.05) by HS compared to control, and PCK1 inhibition with 3MPA attenuated (P < 0.05) its induction by HS. The endoplasmic reticulum (ER) stress markers, C/EBP homologous protein (CHOP) was also upregulated by HS and 3MPA further upregulated (P < 0.05) CHOP mRNA level. These results suggest that with inhibition of PCK1 during HS, in vitro cultured adipocytes were less able to induce adaptive responses such as upregulation of HSP70 and triglycerides, and this exacerbated ER stress during HS. Thus, PCK1 may function to alleviate ER stress that occurs during HS.

An Evaluation of the Performance Diagnostic Checklist-Human Services (PDC-HS) Across Domains.

PubMed

Wilder, David A; Lipschultz, Joshua; Gehrman, Chana

2018-06-01

The Performance Diagnostic Checklist-Human Services (PDC-HS) is an informant-based tool designed to assess the environmental variables that contribute to poor employee performance in human service settings. Although the PDC-HS has been shown to effectively identify variables contributing to problematic performance, interventions based on only two of the four PDC-HS domains have been evaluated to date. In addition, the extent to which PDC-HS-indicated interventions are more effective than nonindicated interventions for two domains remains unclear. In the current study, we administered the PDC-HS to supervisors to assess the variables contributing to infrequent teaching of verbal operants and use of a timer by therapists at a center-based autism treatment program. Each of the four PDC-HS domains was identified as contributing to poor performance for at least one therapist. We then evaluated PDC-HS-indicated interventions for each domain. In addition, to assess the predictive validity of the tool, we evaluated various nonindicated interventions prior to implementing a PDC-HS-indicated intervention for two of the four domains. Results suggest that the PDC-HS-indicated interventions were effective across all four domains and were more effective than the nonindicated interventions for the two domains for which they were evaluated. Results are discussed in terms of the utility of the PDC-HS to identify appropriate interventions to manage therapist performance in human service settings.

Nucleolin is a nuclear target of heparan sulfate derived from glypican-1

DOE Office of Scientific and Technical Information (OSTI.GOV)

Cheng, Fang; Belting, Mattias; Fransson, Lars-Åke

The recycling, S-nitrosylated heparan sulfate (HS) proteoglycan glypican-1 releases anhydromannose (anMan)-containing HS chains by a nitrosothiol-catalyzed cleavage in endosomes that can be constitutive or induced by ascorbate. The HS-anMan chains are then transported to the nucleus. A specific nuclear target for HS-anMan has not been identified. We have monitored endosome-to-nucleus trafficking of HS-anMan by deconvolution and confocal immunofluorescence microscopy using an anMan-specific monoclonal antibody in non-growing, ascorbate-treated, and growing, untreated, wild-type mouse embryonic fibroblasts and hypoxia-exposed Alzheimer mouse Tg2576 fibroblasts and human U87 glioblastoma cells. In all cells, nuclear HS-anMan targeted a limited number of sites of variable size wheremore » it colocalized with DNA and nucleolin, an established marker for nucleoli. HS-anMan also colocalized with ethynyl uridine-tagged nascent RNA and two acetylated forms of histone H3. Acute hypoxia increased the formation of HS-anMan in both Tg2576 and U87 cells. A portion of HS-anMan colocalized with nucleolin at small discrete sites, while most of the nucleolin and nascent RNA was dispersed. In U87 cells, HS-anMan, nucleolin and nascent RNA reassembled after prolonged hypoxia. Nucleolar HS may modulate synthesis and/or release of rRNA.« less

Cooperativeness of the higher chromatin structure of the beta-globin locus revealed by the deletion mutations of DNase I hypersensitive site 3 of the LCR.

PubMed

Fang, Xiangdong; Xiang, Ping; Yin, Wenxuan; Stamatoyannopoulos, George; Li, Qiliang

2007-01-05

High-level transcription of the globin genes requires the enhancement by a distant element, the locus control region (LCR). Such long-range regulation in vivo involves spatial interaction between transcriptional elements, with intervening chromatin looping out. It has been proposed that the clustering of the HS sites of the LCR, the active globin genes, as well as the remote 5' hypersensitive sites (HSs) (HS-60/-62 in mouse, HS-110 in human) and 3'HS1 forms a specific spatial chromatin structure, termed active chromatin hub (ACH). Here we report the effects of the HS3 deletions of the LCR on the spatial chromatin structure of the beta-globin locus as revealed by the chromatin conformation capture (3C) technology. The small HS3 core deletion (0.23 kb), but not the large HS3 deletion (2.3 kb), disrupted the spatial interactions among all the HS sites of the LCR, the beta-globin gene and 3'HS1. We have previously demonstrated that the large HS3 deletion barely impairs the structure of the LCR holocomplex, while the structure is significantly disrupted by the HS3 core deletion. Taken together, these results suggest that the formation of the ACH is dependent on a largely intact LCR structure. We propose that the ACH indeed is an extension of the LCR holocomplex.

Use and safety perceptions regarding herbal supplements: a study of older persons in southeast Idaho.

PubMed

Snyder, Frank J; Dundas, Mary L; Kirkpatrick, Carol; Neill, Karen S

2009-01-01

Herbal supplements (HS) are used by older persons and are often perceived as safe, although there is limited research that examines why this perception exists. A questionnaire was developed and pilot tested to investigate the use and perceived safety of HS among a convenience sample of 112 adults aged 60 to 92 in southeast Idaho. Fifty-five percent of the participants (n = 62) reported using HS in the past. Ninety-five percent (n = 59) of those using HS and 75% (n = 37) of nonusers reported they believed most or some HS were safe. Perception of herbal supplement safety was greatly influenced by family and friends, and HS users had a greater perception of safety than nonusers (p < or = .001). The top reasons for perceived safety given by HS users were that HS: (1) can be purchased without a prescription, (2) can be purchased in many locations, and (3) are natural.

A novel murmur-based heart sound feature extraction technique using envelope-morphological analysis

NASA Astrophysics Data System (ADS)

Yao, Hao-Dong; Ma, Jia-Li; Fu, Bin-Bin; Wang, Hai-Yang; Dong, Ming-Chui

2015-07-01

Auscultation of heart sound (HS) signals serves as an important primary approach to diagnose cardiovascular diseases (CVDs) for centuries. Confronting the intrinsic drawbacks of traditional HS auscultation, computer-aided automatic HS auscultation based on feature extraction technique has witnessed explosive development. Yet, most existing HS feature extraction methods adopt acoustic or time-frequency features which exhibit poor relationship with diagnostic information, thus restricting the performance of further interpretation and analysis. Tackling such a bottleneck problem, this paper innovatively proposes a novel murmur-based HS feature extraction method since murmurs contain massive pathological information and are regarded as the first indications of pathological occurrences of heart valves. Adapting discrete wavelet transform (DWT) and Shannon envelope, the envelope-morphological characteristics of murmurs are obtained and three features are extracted accordingly. Validated by discriminating normal HS and 5 various abnormal HS signals with extracted features, the proposed method provides an attractive candidate in automatic HS auscultation.

Single-Nucleosome Mapping of Histone Modifications in S. cerevisiae

PubMed Central

Kim, Minkyu; Buratowski, Stephen; Schreiber, Stuart L; Friedman, Nir

2005-01-01

Covalent modification of histone proteins plays a role in virtually every process on eukaryotic DNA, from transcription to DNA repair. Many different residues can be covalently modified, and it has been suggested that these modifications occur in a great number of independent, meaningful combinations. Published low-resolution microarray studies on the combinatorial complexity of histone modification patterns suffer from confounding effects caused by the averaging of modification levels over multiple nucleosomes. To overcome this problem, we used a high-resolution tiled microarray with single-nucleosome resolution to investigate the occurrence of combinations of 12 histone modifications on thousands of nucleosomes in actively growing S. cerevisiae. We found that histone modifications do not occur independently; there are roughly two groups of co-occurring modifications. One group of lysine acetylations shows a sharply defined domain of two hypo-acetylated nucleosomes, adjacent to the transcriptional start site, whose occurrence does not correlate with transcription levels. The other group consists of modifications occurring in gradients through the coding regions of genes in a pattern associated with transcription. We found no evidence for a deterministic code of many discrete states, but instead we saw blended, continuous patterns that distinguish nucleosomes at one location (e.g., promoter nucleosomes) from those at another location (e.g., over the 3′ ends of coding regions). These results are consistent with the idea of a simple, redundant histone code, in which multiple modifications share the same role. PMID:16122352

HS3 Data Catalog

NASA Technical Reports Server (NTRS)

Emory, Amber Elizabeth; Chirica, Dan Cristian; Doyle, Jim

2013-01-01

This presentation covered the original plan for the Hurricane and Severe Storm Sentinel (HS3) Data Catalog available through the ESPO HS3 mission page (http://espo.nasa.gov/missions/hs3/) and provided examples of Model Products, Operational Products, and Research (Instrument) Products from the 2012 field campaign. The presentation also covered lessons learned and suggested improvements to the Data Catalog for the upcoming 2013 HS3 field campaign.

Identification of diagnostic biomarkers and metabolic pathway shifts of heat-stressed lactating dairy cows.

PubMed

Tian, He; Wang, Weiyu; Zheng, Nan; Cheng, Jianbo; Li, Songli; Zhang, Yangdong; Wang, Jiaqi

2015-07-01

Controlling heat stress (HS) is a global challenge for the dairy industry. However, simple and reliable biomarkers that aid the diagnoses of HS-induced metabolic disorders have not yet been identified. In this work, an integrated metabolomic and lipidomic approach using (1)H nuclear magnetic resonance and ultra-fast LC-MS was employed to investigate the discrimination of plasma metabolic profiles between HS-free and HS lactating dairy cows. Targeted detection using LC-MS in multiple reaction monitoring mode was used to verify the reliability of the metabolites as biomarker candidates. Overall, 41 metabolites were identified as candidates for lactating dairy cows exposed to HS, among which 13 metabolites, including trimethylamine, glucose, lactate, betaine, creatine, pyruvate, acetoacetate, acetone, β-hydroxybutyrate, C16 sphinganine, lysophosphatidylcholine (18:0), phosphatidylcholine (16:0/14:0), and arachidonic acid, had high sensitivity and specificity in diagnosing HS status, and are likely to be the potential biomarkers of HS dairy cows. All of these potentially diagnostic biomarkers were involved in carbohydrate, amino acid, lipid, or gut microbiome-derived metabolism, indicating that HS affected the metabolic pathways in lactating dairy cows. Further research is warranted to evaluate these biomarkers in practical applications and to elucidate the physiological mechanisms of HS-induced metabolic disorders. Heat stress (HS) annually causes huge losses to global dairy industry, including animal performance decrease, metabolic disorder and health problem. So far, physiological mechanisms underlying HS of dairy cows still remain elusive. To our best knowledge, this is the first attempt to elucidate the HS-induced metabolic disorders of dairy cows using integrated (1)H NMR and LC-MS-based metabolic study. The results not only provided potential diagnostic biomarkers for HS lactating dairy cows, but also significantly explored the related physiological mechanisms of metabolic pathway shifts induced by HS environment. This work offers comprehensive insights into the global metabolic alterations of dairy cows exposed to HS and provides a new perspective for further study. Copyright © 2015 Elsevier B.V. All rights reserved.

Plasma-based proteomics reveals immune response, complement and coagulation cascades pathway shifts in heat-stressed lactating dairy cows.

PubMed

Min, Li; Cheng, Jianbo; Zhao, Shengguo; Tian, He; Zhang, Yangdong; Li, Songli; Yang, Hongjian; Zheng, Nan; Wang, Jiaqi

2016-09-02

Heat stress (HS) has an enormous economic impact on the dairy industry. In recent years, many researchers have investigated changes in the gene expression and metabolomics profiles in dairy cows caused by HS. However, the proteomics profiles of heat-stressed dairy cows have not yet been completely elucidated. We compared plasma proteomics from HS-free and heat-stressed dairy cows using an iTRAQ labeling approach. After the depletion of high abundant proteins in the plasma, 1472 proteins were identified. Of these, 85 proteins were differentially abundant in cows exposed to HS relative to HS-free. Database searches combined with GO and KEGG pathway enrichment analyses revealed that many components of the complement and coagulation cascades were altered in heat-stressed cows compared with HS-free cows. Of these, many factors in the complement system (including complement components C1, C3, C5, C6, C7, C8, and C9, complement factor B, and factor H) were down-regulated by HS, while components of the coagulation system (including coagulation factors, vitamin K-dependent proteins, and fibrinogens) were up-regulated by HS. In conclusion, our results indicate that HS decreases plasma levels of complement system proteins, suggesting that immune function is impaired in dairy cows exposed to HS. Though many aspects of heat stress (HS) have been extensively researched, relatively little is known about the proteomics profile changes that occur during heat exposure. In this work, we employed a proteomics approach to investigate differential abundance of plasma proteins in HS-free and heat-stressed dairy cows. Database searches combined with GO and KEGG pathway enrichment analyses revealed that HS resulted in a decrease in complement components, suggesting that heat-stressed dairy cows have impaired immune function. In addition, through integrative analyses of proteomics and previous metabolomics, we showed enhanced glycolysis, lipid metabolic pathway shifts, and nitrogen repartitioning in dairy cows exposed to HS. Our findings expand our current knowledge on the effects of HS on plasma proteomics in dairy cows and offer a new perspective for future research. Copyright © 2016 Elsevier B.V. All rights reserved.

Trunk muscle activation in the back and hack squat at the same relative loads.

PubMed

Clark, David R; Lambert, Michael I; Hunter, Angus M

2017-07-12

The hack squat (HS) is likely to produce a greater 1 repetition maximum (1RM) compared to the back squat (BS). This can be attributed to the support of the trunk during the HS compared to no support during BS. This support however, may compromise trunk muscle activation (TMA), therefore producing different training adaptations. Accordingly, the purpose of this study was to compare 1RM in BS and HS and TMA at 4 relative loads, 65, 75, 85 and 95% of maximal system mass. Ten males completed 3 test sessions:1) BS and HS 1RM, 2) HS & BS neuromuscular test familiarization, and, 3) Neuromuscular test for 3 reps at 4 loads for BS and HS. BS TMA was significantly greater (p<0.05) than HS for all muscles and phases except rectus abdominus in concentric phase. TMA increased (p<0.05) with load in all muscles for both exercises and phases apart from lumbar sacral erector spinae in HS eccentric phase. Mean HS 1RM and submaximal loads were significantly (p<0.0001) higher than the equivalent BS loads. Duration of the eccentric phase was higher (p<0.01) in HS than BS but not different in concentric phase. Duration increased significantly (p<0.01) with load in both exercises and both phases. Despite higher absolute tests loads in HS, TMA was higher in BS. TMA is sensitive to load in both exercises. BS is more effective than HS in activating the muscles of the trunk and therefore arguably more effective in developing trunk strength and stability for dynamic athletic performance.

Risk Factors for Hidradenitis Suppurativa in Patients with Inflammatory Bowel Disease.

PubMed

Lukach, Alexis J; Saul, Melissa I; Ferris, Laura K; Swoger, Jason M

2018-03-01

Hidradenitis suppurativa (HS) is a chronic inflammatory skin disorder characterized by recurrent nodules, abscesses, and sinus tracts that can be debilitating and significantly impair quality of life. Small studies and case reports have suggested a possible association between HS and inflammatory bowel disease (IBD). We performed a case-control study to further characterize IBD patients with HS in terms of smoking status, BMI, sites affected by HS, IBD type and features, and IBD medication history. A total of 38 patients with HS and IBD were identified and matched on age, gender, and IBD type to 136 controls with IBD but not HS. Clinical characteristics of interest were obtained through extensive review of the electronic health record. Among patients with HS and IBD, the most common sites affected by HS were the inguinal, perianal, and axillary regions. Relative to patients with IBD alone, patients with HS and IBD were nearly six times more likely to be current smokers (p < 0.01) and nearly 11 times more likely to be obese (p < 0.01). Patients with HS and Crohn's were significantly more likely to have ileocolonic and perianal disease than patients with CD only (OR 8.31, 95% CI 2.90-23.80 and OR 2.85, 95% CI 1.19-6.81, respectively; p < 0.01 for both). Relative to patients with IBD who do not develop HS, patients with IBD and HS are more likely to be overweight or obese, to be former or current smokers, and to have ileocolonic and/or perianal disease.

Pathology-Based Approach to Seizure Outcome After Surgery for Pharmacoresistant Medial Temporal Lobe Epilepsy.

PubMed

Martinoni, Matteo; Berti, Pier Paolo; Marucci, Gianluca; Rubboli, Guido; Volpi, Lilia; Riguzzi, Patrizia; Marliani, Federica; Toni, Francesco; Bisulli, Francesca; Tinuper, Paolo; Michelucci, Roberto; Baruzzi, Agostino; Giulioni, Marco

2016-06-01

Hippocampal sclerosis (HS) is the most common cause of drug-resistant medial temporal lobe epilepsy (MTLE). Structural abnormalities such as HS, granule cell pathology (GCP), and focal cortical dysplasia (FCD) have been classified histopathologically, possibly allowing a more accurate assessment of prognostic seizure and neuropsychologic outcomes. We correlated seizure outcome with comprehensive temporal lobe pathologic findings, identified according to the most recent classification systems of HS, GCP, and FCD. All the 83 patients who underwent anterior temporal lobectomy (ATL) for drug-resistant MTLE and with a proven diagnosis of HS between April 2001 and May 2014 were collected. Patients were divided in 2 main groups: 1) isolated HS with/without GCP (HS +/- GCP); and 2) HS associated with FCD with/without GCP (HS+FCD +/- GCP). Patients were followed up at least 1 year, and seizure outcome was reported in accordance with Engel classification. Group I: HS +/- GCP: Statistical analysis confirmed a better outcome in HS + GCP patients than in HS-no GCP (P < 0.05). Moreover, a better outcome for the patients affected by GCP type I was observed (P < 0.05). Group II: HS+FCD +/- GCP: Patients with HS variant type I presented a better seizure outcome than the patients with HS type II (Engel class IA HS type I vs. type II: 69% vs. 40%). A pathology-based approach to epilepsy surgery might improve the interpretation of the results, could predict which cases will enjoy a better seizure outcome, and could help to the comprehension of the causes of failures. Copyright © 2016 Elsevier Inc. All rights reserved.

Guided filter and principal component analysis hybrid method for hyperspectral pansharpening

NASA Astrophysics Data System (ADS)

Qu, Jiahui; Li, Yunsong; Dong, Wenqian

2018-01-01

Hyperspectral (HS) pansharpening aims to generate a fused HS image with high spectral and spatial resolution through integrating an HS image with a panchromatic (PAN) image. A guided filter (GF) and principal component analysis (PCA) hybrid HS pansharpening method is proposed. First, the HS image is interpolated and the PCA transformation is performed on the interpolated HS image. The first principal component (PC1) channel concentrates on the spatial information of the HS image. Different from the traditional PCA method, the proposed method sharpens the PAN image and utilizes the GF to obtain the spatial information difference between the HS image and the enhanced PAN image. Then, in order to reduce spectral and spatial distortion, an appropriate tradeoff parameter is defined and the spatial information difference is injected into the PC1 channel through multiplying by this tradeoff parameter. Once the new PC1 channel is obtained, the fused image is finally generated by the inverse PCA transformation. Experiments performed on both synthetic and real datasets show that the proposed method outperforms other several state-of-the-art HS pansharpening methods in both subjective and objective evaluations.

A pediatrician's practical guide to diagnosing and treating hereditary spherocytosis in neonates.

PubMed

Christensen, Robert D; Yaish, Hassan M; Gallagher, Patrick G

2015-06-01

Newborn infants who have hereditary spherocytosis (HS) can develop anemia and hyperbilirubinemia. Bilirubin-induced neurologic dysfunction is less likely in these neonates if the diagnosis of HS is recognized and appropriate treatment provided. Among neonates listed in the USA Kernicterus Registry, HS was the third most common underlying hemolytic condition after glucose-6-phosphate dehydrogenase deficiency and ABO hemolytic disease. HS is the leading cause of direct antiglobulin test (direct Coombs) negative hemolytic anemia requiring erythrocyte transfusion in the first months of life. We anticipate that as physicians become more familiar with diagnosing HS in the newborn period, fewer neonates with HS will develop hazardous hyperbilirubinemia or present to emergency departments with unanticipated symptomatic anemia. We predict that early suspicion, prompt diagnosis and treatment, and anticipatory guidance will prevent adverse outcomes in neonates with HS. The purpose of this article was to review the neonatal presentation of HS and to provide practical and up-to-date means of diagnosing and treating HS in neonates. Copyright © 2015 by the American Academy of Pediatrics.

Tungstate-induced color-pattern modifications of butterfly wings are independent of stress response and ecdysteroid effect.

PubMed

Otaki, Joji M; Ogasawara, Tsuyoshi; Yamamoto, Haruhiko

2005-06-01

Systemic injections of sodium tungstate, a protein-tyrosine phosphatase (PTPase) inhibitor, to pupae immediately after pupation have been shown to efficiently produce characteristic color-pattern modifications on the wings of many species of butterflies. Here we demonstrated that the tungstate-induced modification pattern was entirely different from other chemically-induced ones in a species of nymphalid butterfly Junonia (Precis) orithya. In this species, the systemic injections of tungstate produced characteristic expansion of black area and shrinkage of white area together with the move of parafocal elements toward the wing base. Overall, pattern boundaries became obscure. In contrast, an entirely different modification pattern, overall darkening of wings, was observed by the injections of stress-inducing chemicals, thapsigargin, ionomycin, or geldanamycin, to pupae under the rearing conditions for the adult summer form. On the ventral wings, this darkening was due to an increase of the proportion of peppered dark scales, which was reminiscent of the natural fall form of this species. Under the same rearing conditions, the injections of ecdysteroid, which is a well-known hormone being responsible for the seasonal polyphenism of nymphalid butterflies, yielded overall expansion of orange area especially around eyespots. Taken together, we conclude that the tungstate-induced modifications are clearly distinguishable from those of stress response and ecdysteroid effect. This conclusion then suggests that the putative PTPase signaling pathway that is sensitive to tungstate uniquely contributes to the wing-wide color-pattern development in butterflies.

Estimating landscape carrying capacity through maximum clique analysis

USGS Publications Warehouse

Donovan, Therese; Warrington, Greg; Schwenk, W. Scott; Dinitz, Jeffrey H.

2012-01-01

Habitat suitability (HS) maps are widely used tools in wildlife science and establish a link between wildlife populations and landscape pattern. Although HS maps spatially depict the distribution of optimal resources for a species, they do not reveal the population size a landscape is capable of supporting--information that is often crucial for decision makers and managers. We used a new approach, "maximum clique analysis," to demonstrate how HS maps for territorial species can be used to estimate the carrying capacity, N(k), of a given landscape. We estimated the N(k) of Ovenbirds (Seiurus aurocapillus) and bobcats (Lynx rufus) in an 1153-km2 study area in Vermont, USA. These two species were selected to highlight different approaches in building an HS map as well as computational challenges that can arise in a maximum clique analysis. We derived 30-m2 HS maps for each species via occupancy modeling (Ovenbird) and by resource utilization modeling (bobcats). For each species, we then identified all pixel locations on the map (points) that had sufficient resources in the surrounding area to maintain a home range (termed a "pseudo-home range"). These locations were converted to a mathematical graph, where any two points were linked if two pseudo-home ranges could exist on the landscape without violating territory boundaries. We used the program Cliquer to find the maximum clique of each graph. The resulting estimates of N(k) = 236 Ovenbirds and N(k) = 42 female bobcats were sensitive to different assumptions and model inputs. Estimates of N(k) via alternative, ad hoc methods were 1.4 to > 30 times greater than the maximum clique estimate, suggesting that the alternative results may be upwardly biased. The maximum clique analysis was computationally intensive but could handle problems with < 1500 total pseudo-home ranges (points). Given present computational constraints, it is best suited for species that occur in clustered distributions (where the problem can be broken into several, smaller problems), or for species with large home ranges relative to grid scale where resampling the points to a coarser resolution can reduce the problem to manageable proportions.

MARCC (Matrix-Assisted Reader Chromatin Capture): an antibody-free method to enrich and analyze combinatorial nucleosome modifications

PubMed Central

Su, Zhangli

2016-01-01

Combinatorial patterns of histone modifications are key indicators of different chromatin states. Most of the current approaches rely on the usage of antibodies to analyze combinatorial histone modifications. Here we detail an antibody-free method named MARCC (Matrix-Assisted Reader Chromatin Capture) to enrich combinatorial histone modifications. The combinatorial patterns are enriched on native nucleosomes extracted from cultured mammalian cells and prepared by micrococcal nuclease digestion. Such enrichment is achieved by recombinant chromatin-interacting protein modules, or so-called reader domains, which can bind in a combinatorial modification-dependent manner. The enriched chromatin can be quantified by western blotting or mass spectrometry for the co-existence of histone modifications, while the associated DNA content can be analyzed by qPCR or next-generation sequencing. Altogether, MARCC provides a reproducible, efficient and customizable solution to enrich and analyze combinatorial histone modifications. PMID:26131849

Heparin octasaccharide decoy liposomes inhibit replication of multiple viruses.

PubMed

Hendricks, Gabriel L; Velazquez, Lourdes; Pham, Serena; Qaisar, Natasha; Delaney, James C; Viswanathan, Karthik; Albers, Leila; Comolli, James C; Shriver, Zachary; Knipe, David M; Kurt-Jones, Evelyn A; Fygenson, Deborah K; Trevejo, Jose M; Wang, Jennifer P; Finberg, Robert W

2015-04-01

Heparan sulfate (HS) is a ubiquitous glycosaminoglycan that serves as a cellular attachment site for a number of significant human pathogens, including respiratory syncytial virus (RSV), human parainfluenza virus 3 (hPIV3), and herpes simplex virus (HSV). Decoy receptors can target pathogens by binding to the receptor pocket on viral attachment proteins, acting as 'molecular sinks' and preventing the pathogen from binding to susceptible host cells. Decoy receptors functionalized with HS could bind to pathogens and prevent infection, so we generated decoy liposomes displaying HS-octasaccharide (HS-octa). These decoy liposomes significantly inhibited RSV, hPIV3, and HSV infectivity in vitro to a greater degree than the original HS-octa building block. The degree of inhibition correlated with the density of HS-octa displayed on the liposome surface. Decoy liposomes with HS-octa inhibited infection of viruses to a greater extent than either full-length heparin or HS-octa alone. Decoy liposomes were effective when added prior to infection or following the initial infection of cells in vitro. By targeting the well-conserved receptor-binding sites of HS-binding viruses, decoy liposomes functionalized with HS-octa are a promising therapeutic antiviral agent and illustrate the utility of the liposome delivery platform. Copyright © 2015 Elsevier B.V. All rights reserved.

The role of lymph factors in lung injury, bone marrow suppression, and endothelial cell dysfunction in a primate model of trauma-hemorrhagic shock.

PubMed

Deitch, Edwin A; Forsythe, Raquel; Anjaria, Dev; Livingston, David H; Lu, Qi; Xu, Da-Zhong; Redl, Heinz

2004-09-01

Studies in rodent models of trauma-hemorrhagic shock (T/HS) have shown that factors contained in the intestinal lymph are responsible for acute lung injury and bone marrow suppression, and that they contribute to a systemic inflammatory state. Because results observed in rodent T/HS models may not fully reflect the response of injured patients, it is necessary to determine if these results can be replicated in primates before the institution of invasive studies in humans. Thus, the three goals of this study were to determine if diversion of thoracic duct lymph reduced T/HS-induced lung injury; to compare the biologic activity of thoracic duct lymph from baboons subjected to T/HS or trauma sham-shock (T/SS); and to compare the biologic activity and composition of plasma from baboons subjected to T/SS, T/HS, and T/HS with thoracic duct lymph drainage. Three groups of baboons were studied: T/SS plus lymph diversion via a thoracic duct catheter, T/HS, and T/HS plus lymph diversion (T/HS-LD). The trauma component consisted of a neck dissection with resection of the proximal clavicle plus a laparotomy. HS was to a mean arterial pressure of 40 mmHg and was maintained at 40 mmHg until the base excess reached -5 mEq or the total shock period reached 3 h. Volume resuscitation was carried out by reinfusing the shed blood plus crystalloids. Before, during, and after the T/HS or T/SS period, blood and lymph samples were obtained for analysis, and lung samples were harvested for measurement of lung wet-to-dry ratio at 5 h after the end of the shock period. Diversion of thoracic duct lymph prevented T/HS-induced lung injury as reflected in lung wet-to-dry weight ratios (T/SS = 4.6 +/- 0.5; T/HS+LD = 4.8 +/- 0.7; T/HS = 5.4 +/- 0.6; P < 0.05). Lymph from the T/HS group collected during the early postshock period was cytotoxic for human endothelial cells (HUVECs; 16% vs. 100% survival in T/SS lymph) and increased HUVEC monolayer permeability almost 2-fold (P < 0.01). T/HS lymph and plasma also suppressed red blood cell (erythroid burst-forming unit) and white blood cell (granulocyte-monocyte colony-forming unit) progenitor cell growth of human bone marrow to approximately 50% of control, whereas T/SS lymph and plasma were not suppressive (P < 0.05). Plasma cytokine levels were increased to a similar degree in the two T/HS groups. Thus, in a primate model of T/HS, gut-derived factors carried in the lymph potentiates lung injury and endothelial dysfunction, and suppresses bone marrow progenitor cell growth.

VizieR Online Data Catalog: i filter photometry for HATS-25 through HATS-30 (Espinoza+, 2016)

NASA Astrophysics Data System (ADS)

Espinoza, N.; Bayliss, D.; Hartman, J. D.; Bakos, G. A.; Jordan, A.; Zhou, G.; Mancini, L.; Brahm, R.; Ciceri, S.; Bhatti, W.; Csubry, Z.; Rabus, M.; Penev, K.; Bento, J.; de Val-Borro, M.; Henning, T.; Schmidt, B.; Suc, V.; Wright, D. J.; Tinney, C. G.; Tan, T. G.; Noyes, R.

2017-05-01

The photometric detection data of the six exoplanets come from the three HATSouth sites, namely, the site at Las Campanas Observatory in Chile (LCO, whose stations are designated HS-1 and HS-2), the site at of the High Energy Spectroscopic Survey (HESS) in Namibia (whose stations are designated HS-3 and HS-4) and the site at the Siding Spring Observatory (SSO) in Australia whose stations are designated HS-5 and HS-6). HATS-25 was observed with an r SDSS filter on 2011 Mar-2011 Aug using HS-2.1, on 2011 Jul-2011 Aug using HS-4.1, and on 2011 May with HS-6.1. HATS-26 was observed with an r SDSS filter on 2012 Feb-2012 Jun using HS-2.3, HS-4.3, and HS-6.3. HATS-27 was observed with an r SDSS filter on 2011 Apr-2012 Jul using HS-2.1, on 2011 Jul-2012 Jul using HS-4.1, and on 2011 May-2012 Jul using HS-6.1. HATS-28 was observed with an r SDSS filter on 2013 Mar-2013 Oct using HS-1.2, on 2013 Sep-2013 Oct using HS-2.2, on 2013 Apr-2013 Nov using HS-3.2, on 2013 Sep-2013 Nov using HS-4.2 and HS-6.2, and 2013 Mar-2013 Nov using HS-5.2. HATS-29 was observed with an r SDSS filter on 2013 Apr-2013 May using HS-1.1, on 2013 Sep-2013 Oct using HS-2.1, on 2013 Apr-2013 Nov using HS-3.1, on 2013 Sep-2013 Nov using HS-4.1 and HS-6.1, and on 2013 Mar-2013 Nov using HS-5.1. HATS-30 was observed using an r SDSS filter on 2012 Sep-2012 Dec using HS-2.3, HS-6.3 and HS-2.4, on 2012 Sep-2013 Jan using HS-4.4, on 2012 Sep-2012 Dec using HS-6.4, and on 2011 Jul-2012 Oct using HS-1.1, HS-3.1 and HS-5.1. Photometric follow-up for the six systems was obtained mainly from 1m-class telescopes at different sites of the Las Cumbres Observatory Global Telescope (LCOGT) network, using the i filter. In particular, one partial transit and a full transit was observed for HATS-25b on 2015 February 23 at Cerro Tololo Inter-American Observatory (CTIO) and 2015 March 16 at SSO, respectively; three partial transits were observed for HATS-26b on 2015 April 19 and 2015 May 21 at CTIO, and 2015 June 04 at SSO; one full transit was observed for HATS-27b on 2015 April 09 at SSO; two partial transits were observed for HATS-28b on 2015 August 31 and 2015 September 03 at CTIO; one full transit and a partial transit were observed for HATS-29b on 2015 and 2014 June, respectively, at CTIO; and two partial transits were observed for HATS-30b on 2014 October 19 at South African Astronomical Observatory (SAAO) and on 2014 Oct 23 at CTIO. In addition, one full transit of HATS-27b was observed using the 0.3m Perth Exoplanet Survey Telescope (PEST) on 2015 March 12 using a RC filter. The reconnaissance spectroscopy of our candidates was made using the Wide Field Spectrograph (WiFeS), located on the Australian National University (ANU) 2.3m telescope. The observing strategy usually consists of taking data with two resolutions: R=λ/Δλ=7000 (medium) and R=3000 (low). For HATS-25, four medium resolution spectra (2014 Jun-Aug) and one low resolution spectrum (2014 Aug 5) were obtained. For HATS-26, two medium resolution spectra (2014 Jun 3-5) and one low resolution spectrum (2014 Jun 4) were obtained. For HATS-27, three medium resolution (2014 Jun 3-5) and one low resolution (2014 Jun 2) spectra were obtained. For HATS-28, only one low resolution spectrum (2015 Jun 1) was obtained. For HATS-29, four medium resolution spectra (2014 Dec-2015 Mar) and one low resolution spectrum (2015 Mar 2) were obtained. For HATS-30, three medium resolution spectra (2014 Oct 4-10) and one low resolution spectrum (2014 Oct 4) were obtained. High-precision spectroscopy was obtained for our targets with different instruments. Several R=115000 spectra were taken with the High Accuracy Radial Velocity Planet Searcher (HARPS) on the ESO 3.6m telescope at La Silla Observatory (LSO) between 2015 February and 2016 March in order to obtain high-precision radial velocities for HATS-25, HATS-26, HATS-27, and HATS-29. Spectra with R=48000 were also taken with the Fiber-fed Extended Range Optical Spectrograph (FEROS) mounted on the Max Planck Gesellschaft (MPG) 2.2m telescope at La Silla Observatory (LSO) between 2014 July and 2015 July in order to both extract precise spectroscopic parameters of the host stars and obtain precise radial velocities for all of our targets. In addition, R=60000 spectra were also taken with the CORALIE spectrograph mounted on the 1.2m Euler telescope at LSO between 2014 June and November for HATS-26, HATS-27, HATS-29, and HATS-30. Finally, eight R=70000 spectra were obtained for HATS-29 on 2015 May to measure radial velocities, using the CYCLOPS2 fiber feed with the University College London Echelle Spectrograph (UCLES) on the 3.9m Anglo-Australian Telescope (AAT). (3 data files).

Natural dissolved humic substances increase the lifespan and promote transgenerational resistance to salt stress in the cladoceran Moina macrocopa.

PubMed

Suhett, Albert L; Steinberg, Christian E W; Santangelo, Jayme M; Bozelli, Reinaldo L; Farjalla, Vinicius F

2011-07-01

Evidence has accumulated that humic substances (HS) are not inert biogeochemicals. Rather, they cause stress symptoms and may modulate the life history of aquatic organisms. Nevertheless, it is still not clear how HS interact with additional stressors and if their effects are transgenerational. We tested the interactive effects of HS and salt to cladocerans, discussing their consequences for the persistence in fluctuating environments, such as coastal lagoons. We used life-table experiments to test the effects of natural HS from a polyhumic coastal lagoon (0, 5, 10, 20, 50, and 100 mg dissolved organic carbon (DOC) L(-1)) on the life-history of the cladoceran Moina macrocopa. We further tested the effects of HS (10 mg DOC L(-1)), within and across generations, on the resistance of M. macrocopa to salt stress (5.5 g L(-1)). HS at 5-20 mg DOC L(-1) extended the mean lifespan of M. macrocopa by ~30%. HS also increased body length at maturity by ~4% at 5-50 mg DOC L(-1) and stimulated male offspring production at all tested concentrations. Exposure to HS (even maternal only) alleviated the salt-induced reduction of somatic growth. Co-exposure to HS increased body volume by 12-22% relative to salt-only treatments, while pre-exposure to HS increased body volume by 40-56% in treatments with salt presence, when compared to non-pre-exposed animals. HS at environmentally realistic concentrations, by acting as mild chemical stressors, modify crucial life-history traits of M. macrocopa, favoring its persistence in fluctuating environments. Some of the effects of HS are even transgenerational.

The Antifungal Plant Defensin HsAFP1 Is a Phosphatidic Acid-Interacting Peptide Inducing Membrane Permeabilization

PubMed Central

Cools, Tanne L.; Vriens, Kim; Struyfs, Caroline; Verbandt, Sara; Ramada, Marcelo H. S.; Brand, Guilherme D.; Bloch, Carlos; Koch, Barbara; Traven, Ana; Drijfhout, Jan W.; Demuyser, Liesbeth; Kucharíková, Soňa; Van Dijck, Patrick; Spasic, Dragana; Lammertyn, Jeroen; Cammue, Bruno P. A.; Thevissen, Karin

2017-01-01

HsAFP1, a plant defensin isolated from coral bells (Heuchera sanguinea), is characterized by broad-spectrum antifungal activity. Previous studies indicated that HsAFP1 binds to specific fungal membrane components, which had hitherto not been identified, and induces mitochondrial dysfunction and cell membrane permeabilization. In this study, we show that HsAFP1 reversibly interacts with the membrane phospholipid phosphatidic acid (PA), which is a precursor for the biosynthesis of other phospholipids, and to a lesser extent with various phosphatidyl inositol phosphates (PtdInsP’s). Moreover, via reverse ELISA assays we identified two basic amino acids in HsAFP1, namely histidine at position 32 and arginine at position 52, as well as the phosphate group in PA as important features enabling this interaction. Using a HsAFP1 variant, lacking both amino acids (HsAFP1[H32A][R52A]), we showed that, as compared to the native peptide, the ability of this variant to bind to PA and PtdInsP’s is reduced (≥74%) and the antifungal activity of the variant is reduced (≥2-fold), highlighting the link between PA/PtdInsP binding and antifungal activity. Using fluorescently labelled HsAFP1 in confocal microscopy and flow cytometry assays, we showed that HsAFP1 accumulates at the cell surface of yeast cells with intact membranes, most notably at the buds and septa. The resulting HsAFP1-induced membrane permeabilization is likely to occur after HsAFP1’s internalization. These data provide novel mechanistic insights in the mode of action of the HsAFP1 plant defensin. PMID:29209301

In utero heat stress increases postnatal core body temperature in pigs.

PubMed

Johnson, J S; Sanz Fernandez, M V; Seibert, J T; Ross, J W; Lucy, M C; Safranski, T J; Elsasser, T H; Kahl, S; Rhoads, R P; Baumgard, L H

2015-09-01

In utero heat stress (IUHS) negatively impacts postnatal development, but how it alters future body temperature parameters and energetic metabolism is not well understood. Future body temperature indices and bioenergetic markers were characterized in pigs from differing in utero thermal environments during postnatal thermoneutral (TN) and cyclical heat stress (HS) exposure. First-parity pregnant gilts ( = 13) were exposed to 1 of 4 ambient temperature (T) treatments (HS [cyclic 28°C to 34°C] or TN [cyclic 18°C to 22°C]) applied for the entire gestation (HSHS, TNTN), HS for the first half of gestation (HSTN), or HS for the second half of gestation (TNHS). Twenty-four offspring (23.1 ± 1.2 kg BW; = 6 HSHS, = 6 TNTN, = 6 HSTN, = 6 TNHS) were housed in TN (21.7°C ± 0.7°C) conditions and then exposed to 2 separate but similar HS periods (HS1 = 6 d; HS2 = 6 d; cycling 28°C to 36°C). Core body temperature (T) was assessed every 15 min with implanted temperature recorders. Regardless of in utero treatment, T increased during both HS periods ( = 0.01; 0.58°C). During TN, HS1, and HS2, all IUHS pigs combined had increased T ( = 0.01; 0.36°C, 0.20°C, and 0.16°C, respectively) compared to TNTN controls. Although unaffected by in utero environment, the total plasma thyroxine to triiodothyronine ratio was reduced ( = 0.01) during HS1 and HS2 (39% and 29%, respectively) compared with TN. In summary, pigs from IUHS maintained an increased T compared with TNTN controls regardless of external T, and this thermal differential may have practical implications to developmental biology and animal bioenergetics.

Transiently enhanced LPS-induced fever following hyperthermic stress in rabbits

NASA Astrophysics Data System (ADS)

Shibata, Masaaki; Uno, Tadashi; Riedel, Walter; Nishimaki, Michiyo; Watanabe, Kaori

2005-11-01

Hyperthermia has been shown to induce an enhanced febrile response to the bacterial-derived endotoxin lipopolysaccharide (LPS). The aim of the present study was to test the hypothesis that the enhanced LPS-induced fever seen in heat stressed (HS) animals is caused by leakage of intestinal bacterial LPS into the circulation. Male rabbits were rendered transiently hyperthermic (a maximum rectal temperature of 43°C) and divided into three groups. They were then allowed to recover in a room at 24°C for 1, 2 or 3 days post-HS. One day after injection with LPS, the post-HS rabbits exhibited significantly higher fevers than the controls, though this was not seen in rabbits at either 2 or 3 days post-HS. The plasma levels of endogenous LPS were significantly increased during the HS as compared to those seen in normothermic rabbits prior to HS. LPS fevers were not induced in these animals. One day post-HS, rabbits that had been pretreated with oral antibiotics exhibited significantly attenuated LPS levels. When challenged with human recombinant interleukin-1β instead of LPS, the 1-day post-HS rabbits did not respond with enhanced fevers. The plasma levels of TNFα increased similarly during LPS-induced fevers in both the control and 1-day post-HS rabbits, while the plasma levels of corticosterone and the osmolality of the 1-day post-HS rabbits showed no significant differences to those seen prior to the HS. These results suggest that the enhanced fever in the 1-day post-HS rabbits is LPS specific, and may be caused by increased leakage of intestinal endotoxin into blood circulation.

Effect of heat shock preconditioning on ROS scavenging activity in rat skeletal muscle after downhill running.

PubMed

Shima, Yosuke; Kitaoka, Katsuhiko; Yoshiki, Yumiko; Maruhashi, Yoshinobu; Tsuyama, Takeshi; Tomita, Katsuro

2008-10-01

The mechanisms of the protective effect conferred by heat shock preconditioning (HS) are currently unknown. The purpose of this study was to determine the effect of HS on muscle injury after downhill running and to address the mechanism of the effect. Female Wistar rats were assigned to three groups: HS, downhill running (E), and downhill running after heat shock preconditioning (HS + E). The HS and HS + E rats were placed in a heat chamber for 60 min (ambient temperature 42 +/- 1.0 degrees C) 48 h before downhill running. Reactive oxygen species (ROS) scavenging activity was determined by electron spin resonance (ESR), and heat shock protein 72 (HSP72) mRNA expression was measured in rat quadriceps femoris. Leukocyte infiltration and degenerated muscle fibers were determined histopathologically. ROS scavenging activity significantly increased at 3 days after HS (151 +/- 18%) and HSP72 mRNA expression increased immediately after HS (1750 +/- 1914%). No decrease in ROS scavenging activity was observed in the HS + E rats at 2 days after exercise compared with the E rats (102 +/- 9% vs. 79 +/- 5%). Degenerated muscle fibers in HS + E rats were significantly less than in E rats at 2, 3, and 7 days after exercise (0.8 +/- 1.0 vs. 2.8 +/- 1.6, 0.8 +/- 1.0 vs. 1.8 +/- 1.6, 0 vs. 0.3 +/- 0.6, respectively). These data demonstrated that HS can reduce muscle injury after downhill running, and this effect may be mediated by increased ROS scavenging activity. Furthermore, HS may protect the antioxidant defense system in skeletal muscle by enhancing the adaptive HSP72 mRNA response.

Printing-assisted surface modifications of patterned ultrafiltration membranes

DOE Office of Scientific and Technical Information (OSTI.GOV)

Wardrip, Nathaniel C.; Dsouza, Melissa; Urgun-Demirtas, Meltem

Understanding and restricting microbial surface attachment will enhance wastewater treatment with membranes. We report a maskless lithographic patterning technique for the generation of patterned polymer coatings on ultrafiltration membranes. Polyethylene glycol, zwitterionic, or negatively charged hydrophilic polymer compositions in parallel- or perpendicular-striped patterns with respect to feed flow were evaluated using wastewater. Membrane fouling was dependent on the orientation and chemical composition of the coatings. Modifications reduced alpha diversity in the attached microbial community (Shannon indices decreased from 2.63 to 1.89) which nevertheless increased with filtration time. Sphingomonas species, which condition membrane surfaces and facilitate cellular adhesion, were depleted inmore » all modified membranes. Microbial community structure was significantly different between control, different patterns, and different chemistries. Lastly, this study broadens the tools for surface modification of membranes with polymer coatings and for understanding and optimization of antifouling surfaces.« less

Printing-assisted surface modifications of patterned ultrafiltration membranes

DOE PAGES

Wardrip, Nathaniel C.; Dsouza, Melissa; Urgun-Demirtas, Meltem; ...

2016-10-17

Understanding and restricting microbial surface attachment will enhance wastewater treatment with membranes. We report a maskless lithographic patterning technique for the generation of patterned polymer coatings on ultrafiltration membranes. Polyethylene glycol, zwitterionic, or negatively charged hydrophilic polymer compositions in parallel- or perpendicular-striped patterns with respect to feed flow were evaluated using wastewater. Membrane fouling was dependent on the orientation and chemical composition of the coatings. Modifications reduced alpha diversity in the attached microbial community (Shannon indices decreased from 2.63 to 1.89) which nevertheless increased with filtration time. Sphingomonas species, which condition membrane surfaces and facilitate cellular adhesion, were depleted inmore » all modified membranes. Microbial community structure was significantly different between control, different patterns, and different chemistries. Lastly, this study broadens the tools for surface modification of membranes with polymer coatings and for understanding and optimization of antifouling surfaces.« less

Intensive herbicide use has selected for constitutively elevated levels of stress-responsive mRNAs and proteins in multiple herbicide-resistant Avena fatua L.

PubMed

Keith, Barbara K; Burns, Erin E; Bothner, Brian; Carey, Charles C; Mazurie, Aurélien J; Hilmer, Jonathan K; Biyiklioglu, Sezgi; Budak, Hikmet; Dyer, William E

2017-11-01

Intensive use of herbicides has led to the evolution of two multiple herbicide-resistant (MHR) Avena fatua (wild oat) populations in Montana that are resistant to members of all selective herbicide families available for A. fatua control in US small grain crops. We used transcriptome and proteome surveys to compare constitutive changes in MHR and herbicide-susceptible (HS) plants associated with non-target site resistance. Compared to HS plants, MHR plants contained constitutively elevated levels of differentially expressed genes (DEGs) with functions in xenobiotic catabolism, stress response, redox maintenance and transcriptional regulation that are similar to abiotic stress-tolerant phenotypes. Proteome comparisons identified similarly elevated proteins including biosynthetic and multifunctional enzymes in MHR plants. Of 25 DEGs validated by RT-qPCR assay, differential regulation of 21 co-segregated with flucarbazone-sodium herbicide resistance in F 3 families, and a subset of 10 of these were induced or repressed in herbicide-treated HS plants. Although the individual and collective contributions of these DEGs and proteins to MHR remain to be determined, our results support the idea that intensive herbicide use has selected for MHR populations with altered, constitutively regulated patterns of gene expression that are similar to those in abiotic stress-tolerant plants. © 2017 Society of Chemical Industry. © 2017 Society of Chemical Industry.

Maternal diet, gestational weight gain, and inflammatory markers during pregnancy.

PubMed

Hrolfsdottir, Laufey; Schalkwijk, Casper G; Birgisdottir, Bryndis E; Gunnarsdottir, Ingibjorg; Maslova, Ekaterina; Granström, Charlotta; Strøm, Marin; Olsen, Sjurdur F; Halldorsson, Thorhallur I

2016-10-01

To examine the associations of gestational weight gain (GWG) and diet with low-grade inflammation in pregnancy. A cross-sectional analysis of 671 pregnant women was performed, and diet was assessed in gestational week 30. GWG was recorded in weeks 30 and ∼37 (difference between the weight recorded at these time points and pre-pregnancy weight). Markers of inflammation, high-sensitivity C-reactive protein (hsCRP), serum amyloid A (SAA), interleukin (IL)-6, IL-8, IL-1β, and tumor necrosis factor-α were quantified in serum from week 30. After adjusting for age, pre-pregnancy BMI, parity, smoking status, and education, each 1 kg increase in GWG was associated with 3% (95% CI: 1-5) higher hsCRP and 3% (95% CI: 1-4) higher SAA concentrations, which corresponded to ∼18% to 25% increase in these biomarkers among those with excessive weight gain. GWG was inversely associated with IL-8 while no associations were found for the other inflammatory markers. With respect to diet, women in the highest compared with lowest quintile of protein intake had 26% (95% CI: 3-54) higher hsCRP concentrations. This increase appeared to be driven by intake of animal protein. A similar pattern was observed for SAA. Excessive GWG, as well as high intake of animal protein, was associated with higher concentrations of inflammatory factors. © 2016 The Obesity Society.

Improved Visualization of Glaucomatous Retinal Damage Using High-speed Ultrahigh-Resolution Optical Coherence Tomography

PubMed Central

Mumcuoglu, Tarkan; Wollstein, Gadi; Wojtkowski, Maciej; Kagemann, Larry; Ishikawa, Hiroshi; Gabriele, Michelle L.; Srinivasan, Vivek; Fujimoto, James G.; Duker, Jay S.; Schuman, Joel S.

2009-01-01

Purpose To test if improving optical coherence tomography (OCT) resolution and scanning speed improves the visualization of glaucomatous structural changes as compared with conventional OCT. Design Prospective observational case series. Participants Healthy and glaucomatous subjects in various stages of disease. Methods Subjects were scanned at a single visit with commercially available OCT (StratusOCT) and high-speed ultrahigh-resolution (hsUHR) OCT. The prototype hsUHR OCT had an axial resolution of 3.4 μm (3 times higher than StratusOCT), with an A-scan rate of 24 000 hertz (60 times faster than StratusOCT). The fast scanning rate allowed the acquisition of novel scanning patterns such as raster scanning, which provided dense coverage of the retina and optic nerve head. Main Outcome Measures Discrimination of retinal tissue layers and detailed visualization of retinal structures. Results High-speed UHR OCT provided a marked improvement in tissue visualization as compared with StratusOCT. This allowed the identification of numerous retinal layers, including the ganglion cell layer, which is specifically prone to glaucomatous damage. Fast scanning and the enhanced A-scan registration properties of hsUHR OCT provided maps of the macula and optic nerve head with unprecedented detail, including en face OCT fundus images and retinal nerve fiber layer thickness maps. Conclusion High-speed UHR OCT improves visualization of the tissues relevant to the detection and management of glaucoma. PMID:17884170

Loss of intra-islet heparan sulfate is a highly sensitive marker of type 1 diabetes progression in humans.

PubMed

Simeonovic, Charmaine J; Popp, Sarah K; Starrs, Lora M; Brown, Debra J; Ziolkowski, Andrew F; Ludwig, Barbara; Bornstein, Stefan R; Wilson, J Dennis; Pugliese, Alberto; Kay, Thomas W H; Thomas, Helen E; Loudovaris, Thomas; Choong, Fui Jiun; Freeman, Craig; Parish, Christopher R

2018-01-01

Type 1 diabetes (T1D) is an autoimmune disease in which insulin-producing beta cells in pancreatic islets are progressively destroyed. Clinical trials of immunotherapies in recently diagnosed T1D patients have only transiently and partially impacted the disease course, suggesting that other approaches are required. Our previous studies have demonstrated that heparan sulfate (HS), a glycosaminoglycan conventionally expressed in extracellular matrix, is present at high levels inside normal mouse beta cells. Intracellular HS was shown to be critical for beta cell survival and protection from oxidative damage. T1D development in Non-Obese Diabetic (NOD) mice correlated with loss of islet HS and was prevented by inhibiting HS degradation by the endoglycosidase, heparanase. In this study we investigated the distribution of HS and heparan sulfate proteoglycan (HSPG) core proteins in normal human islets, a role for HS in human beta cell viability and the clinical relevance of intra-islet HS and HSPG levels, compared to insulin, in human T1D. In normal human islets, HS (identified by 10E4 mAb) co-localized with insulin but not glucagon and correlated with the HSPG core proteins for collagen type XVIII (Col18) and syndecan-1 (Sdc1). Insulin-positive islets of T1D pancreases showed significant loss of HS, Col18 and Sdc1 and heparanase was strongly expressed by islet-infiltrating leukocytes. Human beta cells cultured with HS mimetics showed significantly improved survival and protection against hydrogen peroxide-induced death, suggesting that loss of HS could contribute to beta cell death in T1D. We conclude that HS depletion in beta cells, possibly due to heparanase produced by insulitis leukocytes, may function as an important mechanism in the pathogenesis of human T1D. Our findings raise the possibility that intervention therapy with dual activity HS replacers/heparanase inhibitors could help to protect the residual beta cell mass in patients recently diagnosed with T1D.

Data System for HS3 Airborne Field Campaign

NASA Astrophysics Data System (ADS)

Maskey, M.; Mceniry, M.; Berendes, T.; Bugbee, K.; Conover, H.; Ramachandran, R.

2014-12-01

Hurricane and Severe Storm Sentinel (HS3) is a NASA airborne field campaign aimed at better understanding the physical processes that control hurricane intensity change. HS3 will help answer questions related to the roles of environmental conditions and internal storm structures to storm intensification. Due to the nature of the questions that HS3 mission is addressing, it involves a variety of in-situ, satellite observations, airborne data, meteorological analyses, and simulation data. This variety of datasets presents numerous data management challenges for HS3. The methods used for airborne data management differ greatly from the methods used for space-borne data. In particular, metadata extraction, spatial and temporal indexing, and the large number of instruments and subsequent variables are a few of the data management challenges unique to airborne missions. A robust data system is required to successfully help HS3 scientist achieve their mission goals. Furthermore, the data system also needs to provide for data management that assists in broader use of HS3 data to enable future research activities. The Global Hydrology Resource Center (GHRC) is considering all these needs and designing a data system for HS3. Experience with past airborne field campaign puts GHRC in a good position to address HS3 needs. However, the scale of this mission along with science requirements separates HS3 from previous field campaigns. The HS3 data system will include automated services for geo-location, metadata extraction, discovery, and distribution for all HS3 data. To answer the science questions, the data system will include a visual data exploration tool that is fully integrated into the data catalog. The tool will allow visually augmenting airborne data with analyses and simulations. Satellite data will provide contextual information during such data explorations. All HS3 tools will be supported by an enterprise service architecture that will allow scaling, easy integration of new tools and existing services, and integration of new ESDIS metadata and security guidelines.

Meta-analysis of cannabinoid ligand binding affinity and receptor distribution: interspecies differences

PubMed Central

McPartland, J M; Glass, M; Pertwee, R G

2007-01-01

A meta-analysis, unlike a literature review, synthesizes previous studies into new results. Pooled data from 211 studies measured ligand binding affinities at human (Hs) or rat (Rn) cannabinoid receptors CB1 and CB2. Cochrane methods were modified for this non-clinical analysis. Meta-regression detected data heterogeneity arising from methodological factors: use of sectioned tissues, lack of PMSF and choice of radioligand. Native brain tissues exhibited greater affinity (lower nM) than transfected cells, but the trend fell short of significance, as did the trend between centrifugation and filtration methods. Correcting for heterogeneity, mean Ki values for Δ9-tetrahydrocannabinol differed significantly between HsCB1 and RnCB1 (25.1 and 42.6 nM, respectively) but not between HsCB1 and HsCB2 (25.1 and 35.2). Mean Kd values for HsCB1, RnCB1 and HsCB2 of CP55,940 (2.5, 0.98, 0.92) and WIN55,212-2 (16.7, 2.4, 3.7) differed between HsCB1 and RnCB1 and between HsCB1 and HsCB2. SR141716A differed between HsCB1 and RnCB1 (2.9 and 1.0 nM). Anandamide at HsCB1, RnCB1 and HsCB2 (239.2, 87.7, 439.5) fell short of statistical differences due to heterogeneity. We consider these Kd and Ki values to be the most valid estimates in the literature. Sensitivity analyses did not support the numerical validity of cannabidiol, cannabinol, 2-arachidonoyl glycerol and all ligands at RnCB2. Aggregate rank order analysis of CB1 distribution in the brain (pooled from 119 autoradiographic, immunohistochemical and in situ hybridization studies) showed denser HsCB1 expression in cognitive regions (cerebral cortex) compared to RnCB1, which was relatively richer in movement-associated areas (cerebellum, caudate-putamen). Implications of interspecies differences are discussed. PMID:17641667

Endothelial Heparan Sulfate 6-O-Sulfation Levels Regulate Angiogenic Responses of Endothelial Cells to Fibroblast Growth Factor 2 and Vascular Endothelial Growth Factor*

PubMed Central

Ferreras, Cristina; Rushton, Graham; Cole, Claire L.; Babur, Muhammad; Telfer, Brian A.; van Kuppevelt, Toin H.; Gardiner, John M.; Williams, Kaye J.; Jayson, Gordon C.; Avizienyte, Egle

2012-01-01

Fibroblast growth factor 2 (FGF2) and vascular endothelial growth factor 165 (VEGF165) are potent pro-angiogenic growth factors that play a pivotal role in tumor angiogenesis. The activity of these growth factors is regulated by heparan sulfate (HS), which is essential for the formation of FGF2/FGF receptor (FGFR) and VEGF165/VEGF receptor signaling complexes. However, the structural characteristics of HS that determine activation or inhibition of such complexes are only partially defined. Here we show that ovarian tumor endothelium displays high levels of HS sequences that harbor glucosamine 6-O-sulfates when compared with normal ovarian vasculature where these sequences are also detected in perivascular area. Reduced HS 6-O-sulfotransferase 1 (HS6ST-1) or 6-O-sulfotransferase 2 (HS6ST-2) expression in endothelial cells impacts upon the prevalence of HS 6-O-sulfate moieties in HS sequences, which consist of repeating short, highly sulfated S domains interspersed by transitional N-acetylated/N-sulfated domains. 1–40% reduction in 6-O-sulfates significantly compromises FGF2- and VEGF165-induced endothelial cell sprouting and tube formation in vitro and FGF2-dependent angiogenesis in vivo. Moreover, HS on wild-type neighboring endothelial or smooth muscle cells fails to restore endothelial cell sprouting and tube formation. The affinity of FGF2 for HS with reduced 6-O-sulfation is preserved, although FGFR1 activation is inhibited correlating with reduced receptor internalization. These data show that 6-O-sulfate moieties in endothelial HS are of major importance in regulating FGF2- and VEGF165-dependent endothelial cell functions in vitro and in vivo and highlight HS6ST-1 and HS6ST-2 as potential targets of novel antiangiogenic agents. PMID:22927437

Small lytic peptides escape the inhibitory effect of heparan sulfate on the surface of cancer cells

PubMed Central

2011-01-01

Background Several naturally occurring cationic antimicrobial peptides (CAPs), including bovine lactoferricin (LfcinB), display promising anticancer activities. These peptides are unaffected by multidrug resistance mechanisms and have been shown to induce a protective immune response against solid tumors, thus making them interesting candidates for developing novel lead structures for anticancer treatment. Recently, we showed that the anticancer activity by LfcinB was inhibited by the presence of heparan sulfate (HS) on the surface of tumor cells. Based on extensive structure-activity relationship studies performed on LfcinB, shorter and more potent peptides have been constructed. In the present study, we have investigated the anticancer activity of three chemically modified 9-mer peptides and the influence of HS and chondroitin sulfate (CS) on their cytotoxic activity. Methods Various cell lines and red blood cells were used to investigate the anticancer activity and selectivity of the peptides. The cytotoxic effect of the peptides against the different cell lines was measured by use of a colorimetric MTT viability assay. The influence of HS and CS on their cytotoxic activity was evaluated by using HS/CS expressing and HS/CS deficient cell lines. The ability of soluble HS and CS to inhibit the cytotoxic activity of the peptides and the peptides' affinity for HS and CS were also investigated. Results The 9-mer peptides displayed selective anticancer activity. Cells expressing HS/CS were equally or more susceptible to the peptides than cells not expressing HS/CS. The peptides displayed a higher affinity for HS compared to CS, and exogenously added HS inhibited the cytotoxic effect of the peptides. Conclusions In contrast to the previously reported inhibitory effect of HS on LfcinB, the present study shows that the cytotoxic activity of small lytic peptides was increased or not affected by cell surface HS. PMID:21453492

Effect of fiber content on tensile retention properties of Cellulose Microfiber Reinforced Polymer Composites for Automobile Application

NASA Astrophysics Data System (ADS)

Aseer, J. R.; Sankaranarayanasamy, K.

2017-12-01

Today, the utilization of biodegradable materials has been hogging much attention throughout the world. Due to the disposal issues of petroleum based products, there is a focus towards developing biocomposites with superior mechanical properties and degradation rate. In this research work, Hibiscus Sabdariffa (HS) fibers were used as the reinforcement for making biocomposites. The HS fibers were reinforced in the polyester resin by compression moulding method. Water absorption studies of the composite at room temperature are carried out as per ASTM D 570. Also, degradation behavior of HS/Polyester was done by soil burial method. The HS/polyester biocomposites containing 7.5 wt% of HS fiber has shown higher value of tensile strength. The tensile strength retention of the HS/Polyester composites are higher than the neat polyester composites. This value increases with increase of HS fiber loading in the composites. The results indicated that HS/polyester biocomposites can be used for making automobile components such as bumper guards etc.

A Comparison of Women’s Collegiate and Girls’ High School Volleyball Injury Data Collected Prospectively Over a 4-Year Period

PubMed Central

Reeser, Jonathan C.; Gregory, Andrew; Berg, Richard L.; Comstock, R. Dawn

2015-01-01

Background: There is a relative paucity of research examining the sport-specific injury epidemiology of high school and collegiate volleyball athletes. Moreover, differences in study methodology frequently limit our ability to compare and contrast injury data collected from selected populations. Hypothesis: There are differences between the injury patterns characteristic of high school and collegiate female volleyball athletes. Study Design: Retrospective clinical review. Level of Evidence: Level 3. Methods: We statistically analyzed injury incidence and outcome data collected over a 4-year interval (2005-2006 to 2008-2009) by 2 similar injury surveillance systems, the National Collegiate Athletic Association’s Injury Surveillance System (NCAA ISS) and the High School Reporting Injuries Online (HS RIO). We compared diagnoses, anatomic distribution of injuries, mechanisms of injury, and time lost from training or competition between high school and collegiate volleyball athletes. Results: The overall volleyball-related injury rate was significantly greater among collegiate athletes than among high school athletes during both competition (injury rate ratio, 2.9; 95% CI, 2.5-3.4) and practice (injury rate ratio, 3.5; 95% CI, 3.1-3.9). Collegiate athletes had a higher rate of ankle sprain, knee injury, and shoulder injury. Concussions represented a relatively high percentage of injuries in both populations (5.0% of total NCAA ISS injuries vs 4.8% of total HS RIO injuries, respectively). Conclusion: The data suggest that although similar, there were distinct differences between the injury patterns of the 2 populations. Compared with high school volleyball players, collegiate athletes have a higher rate of acute time loss injury as well as overuse time loss injury (particularly patellar tendinosis). Concussions represented a significant and worrisome component of the injury pattern for both study populations. Clinical Relevance: The injury data suggest that important differences exist in the injury patterns of female high school compared with collegiate volleyball athletes. Consideration of the specific injury patterns may be helpful in future prevention efforts. PMID:26502443

A Comparison of Women's Collegiate and Girls' High School Volleyball Injury Data Collected Prospectively Over a 4-Year Period.

PubMed

Reeser, Jonathan C; Gregory, Andrew; Berg, Richard L; Comstock, R Dawn

2015-01-01

There is a relative paucity of research examining the sport-specific injury epidemiology of high school and collegiate volleyball athletes. Moreover, differences in study methodology frequently limit our ability to compare and contrast injury data collected from selected populations. There are differences between the injury patterns characteristic of high school and collegiate female volleyball athletes. Retrospective clinical review. Level 3. We statistically analyzed injury incidence and outcome data collected over a 4-year interval (2005-2006 to 2008-2009) by 2 similar injury surveillance systems, the National Collegiate Athletic Association's Injury Surveillance System (NCAA ISS) and the High School Reporting Injuries Online (HS RIO). We compared diagnoses, anatomic distribution of injuries, mechanisms of injury, and time lost from training or competition between high school and collegiate volleyball athletes. The overall volleyball-related injury rate was significantly greater among collegiate athletes than among high school athletes during both competition (injury rate ratio, 2.9; 95% CI, 2.5-3.4) and practice (injury rate ratio, 3.5; 95% CI, 3.1-3.9). Collegiate athletes had a higher rate of ankle sprain, knee injury, and shoulder injury. Concussions represented a relatively high percentage of injuries in both populations (5.0% of total NCAA ISS injuries vs 4.8% of total HS RIO injuries, respectively). The data suggest that although similar, there were distinct differences between the injury patterns of the 2 populations. Compared with high school volleyball players, collegiate athletes have a higher rate of acute time loss injury as well as overuse time loss injury (particularly patellar tendinosis). Concussions represented a significant and worrisome component of the injury pattern for both study populations. The injury data suggest that important differences exist in the injury patterns of female high school compared with collegiate volleyball athletes. Consideration of the specific injury patterns may be helpful in future prevention efforts. © 2015 The Author(s).

An in vitro evaluation of the Anew Zephyr open-bag IOL in the prevention of posterior capsule opacification using a human capsular bag model.

PubMed

Eldred, Julie A; Spalton, David J; Wormstone, I Michael

2014-09-18

During cataract surgery an IOL is placed within the capsular bag. Clinical studies show that IOLs with a square edge profile and complete contact between the IOL and the anterior capsule (AC) are currently the best way to prevent posterior capsule opacification (PCO). This has been challenged by recent clinical and experimental observations, which suggest that if the capsular bag is kept open with separation of contact between the AC and posterior capsule (PC) by an "open-bag device" PCO is dramatically reduced. Therefore, the current study set out to evaluate the putative merits of an open-bag IOL (Anew Zephyr) in a human capsular bag model. An in vitro organ culture model using the bag-zonular-ciliary body complex isolated from fellow human donor eyes was prepared. A capsulorhexis and lens extraction were performed, and an Alcon Acrysof IOL or Anew Zephyr IOL implanted. Preparations were secured by pinning the ciliary body to a silicone ring and maintained in 6 mL Eagle's minimum essential medium (EMEM) or EMEM supplemented with 2% vol/vol human serum (HS) and 10 ng/mL TGF-β2 for 28 days. Cell growth and capsular modifications were monitored with phase-contrast and modified dark-field microscopy. In serum-free EMEM culture conditions, cells were observed growing onto the PC of preparations implanted with an Anew Zephyr IOL, but this was retarded relative to observations in match-paired capsular bags implanted with an Alcon Acrysof IOL. In the case of cultures maintained in 2% HS-EMEM plus TGF-β2, the movement on to the PC was again delayed with the presence of an Anew Zephyr IOL. Differences in the degree of growth on the PC and matrix modifications were apparent with the different donors, but in each case the match-paired Alcon Acrysof implanted bag exhibited significantly greater coverage and modification of the capsule. The Anew Zephyr open-bag IOL performs consistently better than the Alcon Acrysof IOL in the human capsular bag model. We propose that the benefits observed with the Anew Zephyr result from a reduction in growth factor levels available within the capsular bag and a barrier function imposed by the ring haptic. Copyright 2014 The Association for Research in Vision and Ophthalmology, Inc.

Effect of diet composition and feeding pattern on the prececal digestibility of starches from diverse botanical origins measured with the mobile nylon bag technique in horses.

PubMed

de Fombelle, A; Veiga, L; Drogoul, C; Julliand, V

2004-12-01

This trial was conducted to determine the extent of prececal starch digestibility depending on the botanical origin of starch and on diet characteristics (i.e., composition and feeding pattern). The prececal disappearance of six substrates (oats, barley, corn, horse bean, potato, and wheat) was measured in four cannulated horses fed (as-fed basis) 11.8 g/kg BW of a high-fiber (HF) or high-starch (HS) pelleted feed and 10.0 g/kg BW of meadow hay using the mobile bag technique (MBT). The daily feeding pattern was either three meals (two meals of pellets and one meal of hay) or five meals (three meals of pellets and two meals of hay). The experimental procedure was a 2 x 2 factorial arrangement tested in a Latin square design. After 2 wk of adaptation to the diet, collections were made on 5 d. Thirty nylon bags, composed of five bags of each substrate, were intubated to each horse during the ingestion of the morning meal. Bags were collected in the cecum, using a magnet, at 9 h postintubation. In spite of strong interindividual differences, approximately 80% of the intubated bags were collected. On average, the mean retention time of the bags was 6.2 h (+/-0.17). Regardless of the feeding pattern, the transit of the bags was faster when the fiber content of the diet was higher (P = 0.003). Likewise, regardless of the meal composition, transit was also faster when the ration was split into five daily meals (P = 0.001). The DM disappearance, corrected with particulate losses (DMD(c)), differed depending on the substrate tested (33.5, 57.1, 63.8, 67.7, 78.6, and 86.2% for potato, horse bean, oats, barley, corn, and wheat, respectively; P = 0.001). The DMD(c) of corn, barley, and potato was higher when HS was fed (P = 0.020); regardless of the substrate, DMD(c) was higher with five daily meals (P = 0.001). The starch disappearance (StarchD(c)) was different depending on the substrate (P = 0.001; 36.1, 71.2, 86.6, 89.2, 99.0, and 99.7% for potato, horse bean, barley, corn, wheat, and oats, respectively). Whatever the substrate, StarchD(c) was higher when HS was fed (P = 0.007), but it was not affected by the feeding pattern of the diet. Although passage rate was modified and feed intake was different, the botanical origin of starch was the main factor that affected prececal starch disappearance in horses.

The Use of the Performance Diagnostic Checklist-Human Services to Assess and Improve the Job Performance of Individuals with Intellectual Disabilities.

PubMed

Smith, Madison; Wilder, David A

2018-06-01

The Performance Diagnostic Checklist-Human Services (PDC-HS) is an informant-based tool designed to identify the variables responsible for performance problems. To date, the PDC-HS has not been examined with individuals with intellectual disabilities. In the current study, two supervisors with intellectual disabilities completed the PDC-HS to assess the productivity of two supervisees with disabilities who performed a pricing task in a thrift store. The PDC-HS suggested that performance deficits were due to a lack of training; a PDC-HS-indicated intervention was effective to increase accurate pricing. • The PDC-HS is an informant-based tool designed to identify the variables responsible for employee performance problems in human service settings. • The PDC-HS can be completed by some individuals with intellectual disabilities in a supervisory position to identify the variables responsible for problematic job performance among their supervisees. • A PDC-HS indicated intervention was demonstrated to be effective to improve the job performance of individuals with disabilities. • The PDC-HS may be a useful tool to support performance improvement and job maintenance among individuals with intellectual disabilities.

Ecological Effects of Weather Modification: A Problem Analysis.

ERIC Educational Resources Information Center

Cooper, Charles F.; Jolly, William C.

This publication reviews the potential hazards to the environment of weather modification techniques as they eventually become capable of producing large scale weather pattern modifications. Such weather modifications could result in ecological changes which would generally require several years to be fully evident, including the alteration of…

Understanding Patterns of Team Collaboration Employed To Solve Unique Problems

DTIC Science & Technology

2008-06-01

ELEMENT NUMBER 6. AUTHOR(S) 5d. PROJECT NUMBER 5e. TASK NUMBER 5f. WORK UNIT NUMBER 7. PERFORMING ORGANIZATION NAME(S) AND ADDRESS(ES) Naval...Postgraduate School,Code IS/Hs,589 Dyer Road,Monterey,CA,93943 8. PERFORMING ORGANIZATION REPORT NUMBER 9. SPONSORING/MONITORING AGENCY NAME(S) AND... organizations , systems, infrastructure, and processes to create and share data, information, and knowledge that is needed for the team to plan

Is hidradenitis suppurativa associated with anaemia?: a population-based and hospital-based cross-sectional study from Denmark.

PubMed

Miller, I M; Johansen, M E; Mogensen, U B; Zarchi, K; Ellervik, C; Jemec, G B

2016-08-01

Chronic inflammatory diseases may be associated with anaemia of inflammation. Hidradenitis suppurativa is a chronic inflammatory dermatological disease associated with metabolic comorbidities, low quality of life and fatigue. Anaemia may cause fatigue, and it has been hypothesized that HS-related fatigue may be partly due to anaemia. Our objective was to investigate a possible association between HS and anaemia. We performed a hospital-based and population-based cross-sectional study investigating the red blood cell profile, i.e. haemoglobin. We identified a total of 32 hospital HS individuals, 430 population HS individuals and 20,780 population non-HS control individuals. The age-sex-smoking-adjusted analyses showed no differences in the haemoglobin level of the HS groups vs. the control group. Analyses of the anaemic subgroup of HS individuals revealed that 60% had normocytic anaemia and 40% microcytic anaemia, in concordance with anaemia of inflammation. In contrast to our hypothesis, this study showed that HS is not associated with anaemia. Thus, anaemia may not be the cause of the described fatigue in HS patients. Furthermore, the results indicate that if an HS patient does suffer from anaemia it is most likely to be normocytic or microcytic and thus compatible with anaemia seen in other chronic inflammatory disorders. © 2015 European Academy of Dermatology and Venereology.

Dimethyl Sulfoxide Attenuates Acute Lung Injury Induced by Hemorrhagic Shock/Resuscitation in Rats.

PubMed

Tsung, Yu-Chi; Chung, Chih-Yang; Wan, Hung-Chieh; Chang, Ya-Ying; Shih, Ping-Cheng; Hsu, Han-Shui; Kao, Ming-Chang; Huang, Chun-Jen

2017-04-01

Inflammation following hemorrhagic shock/resuscitation (HS/RES) induces acute lung injury (ALI). Dimethyl sulfoxide (DMSO) possesses anti-inflammatory and antioxidative capacities. We sought to clarify whether DMSO could attenuate ALI induced by HS/RES. Male Sprague-Dawley rats were allocated to receive either a sham operation, sham plus DMSO, HS/RES, or HS/RES plus DMSO, and these were denoted as the Sham, Sham + DMSO, HS/RES, or HS/RES + DMSO group, respectively (n = 12 in each group). HS/RES was achieved by drawing blood to lower mean arterial pressure (40-45 mmHg for 60 min) followed by reinfusion with shed blood/saline mixtures. All rats received an intravenous injection of normal saline or DMSO immediately before resuscitation or at matching points relative to the sham groups. Arterial blood gas and histological assays (including histopathology, neutrophil infiltration, and lung water content) confirmed that HS/RES induced ALI. Significant increases in pulmonary expression of tumor necrosis factor-α (TNF-α), malondialdehyde, nuclear factor-kappa B (NF-κB), inducible nitric oxide synthase (iNOS), and cyclooxygenase 2 (COX-2) confirmed that HS/RES induced pulmonary inflammation and oxidative stress. DMSO significantly attenuated the pulmonary inflammation and ALI induced by HS/RES. The mechanisms for this may involve reducing inflammation and oxidative stress through inhibition of pulmonary NF-κB, TNF-α, iNOS, and COX-2 expression.

The RecX protein interacts with the RecA protein and modulates its activity in Herbaspirillum seropedicae.

PubMed

Galvão, C W; Souza, E M; Etto, R M; Pedrosa, F O; Chubatsu, L S; Yates, M G; Schumacher, J; Buck, M; Steffens, M B R

2012-12-01

DNA repair is crucial to the survival of all organisms. The bacterial RecA protein is a central component in the SOS response and in recombinational and SOS DNA repairs. The RecX protein has been characterized as a negative modulator of RecA activity in many bacteria. The recA and recX genes of Herbaspirillum seropedicae constitute a single operon, and evidence suggests that RecX participates in SOS repair. In the present study, we show that the H. seropedicae RecX protein (RecX Hs) can interact with the H. seropedicaeRecA protein (RecA Hs) and that RecA Hs possesses ATP binding, ATP hydrolyzing and DNA strand exchange activities. RecX Hs inhibited 90% of the RecA Hs DNA strand exchange activity even when present in a 50-fold lower molar concentration than RecA Hs. RecA Hs ATP binding was not affected by the addition of RecX, but the ATPase activity was reduced. When RecX Hs was present before the formation of RecA filaments (RecA-ssDNA), inhibition of ATPase activity was substantially reduced and excess ssDNA also partially suppressed this inhibition. The results suggest that the RecX Hs protein negatively modulates the RecA Hs activities by protein-protein interactions and also by DNA-protein interactions.

Mannitol versus hypertonic saline: Safety and efficacy of mannitol and hypertonic saline in sputum induction and bronchial hyperreactivity assessment.

PubMed

Alvarez-Puebla, M J; Olaguibel, J M; Almudevar, E; Echegoyen, A A; Vela, C; de Esteban, B

2015-08-01

Eosinophilic asthma phenotype predicts good response to corticosteroids and associates to asthmatic exacerbations. Sputum induction by hypertonic saline (HS) inhalation is technically demanding. Bronchial hyperresponsiveness (BHR) to osmotic agents indirectly mirrors active airway inflammation. We compared the safety and ability of HS and mannitol to induce sputum and measure BHR. We evaluated the stability of inflammatory phenotypes. We studied 35 non-smoking asthmatics randomized to undergo HS and mannitol challenges on 2 days 1 week apart. Sputum was sampled for cell analysis and phenotyped as eosinophilic (≥3% eosinophils) and non-eosinophilic (<3%) asthma. Nineteen subjects had BHR to mannitol and nine of them also had BHR to HS. Drops in forced expiratory volume in 1 s were higher from HS challenge than from mannitol challenge. Adequate sputum samples were obtained from 80% subjects (68% mannitol and 71% HS). Eosinophils and macrophages from both challenges correlated. Neutrophils were higher in sputum from HS. Ninety percent samples were equally phenotyped with HS and mannitol. Fractional exhaled nitric oxide, sputum eosinophils and BHR correlated in both challenges. HS and mannitol showed similar capacity to produce valuable sputum samples. BHR to both osmotic stimuli partially resembled airway eosinophilic inflammation but mannitol was more sensitive than HS to assess BHR. Eosinophilic phenotype remained stable in most patients with both stimuli. © The Author(s) 2015.

Viral and Cellular Determinants of the Hepatitis C Virus Envelope-Heparan Sulfate Interaction▿

PubMed Central

Barth, Heidi; Schnober, Eva K.; Zhang, Fuming; Linhardt, Robert J.; Depla, Erik; Boson, Bertrand; Cosset, Francois-Loic; Patel, Arvind H.; Blum, Hubert E.; Baumert, Thomas F.

2006-01-01

Cellular binding and entry of hepatitis C virus (HCV) are the first steps of viral infection and represent a major target for antiviral antibodies and novel therapeutic strategies. We have recently demonstrated that heparan sulfate (HS) plays a key role in the binding of HCV envelope glycoprotein E2 to target cells (Barth et al., J. Biol. Chem. 278:41003-41012, 2003). In this study, we characterized the HCV-HS interaction and analyzed its inhibition by antiviral host immune responses. Using recombinant envelope glycoproteins, virus-like particles, and HCV pseudoparticles as model systems for the early steps of viral infection, we mapped viral and cellular determinants of HCV-HS interaction. HCV-HS binding required a specific HS structure that included N-sulfo groups and a minimum of 10 to 14 saccharide subunits. HCV envelope binding to HS was mediated by four viral epitopes overlapping the E2 hypervariable region 1 and E2-CD81 binding domains. In functional studies using HCV pseudoparticles, we demonstrate that HCV binding and entry are specifically inhibited by highly sulfated HS. Finally, HCV-HS binding was markedly inhibited by antiviral antibodies derived from HCV-infected individuals. In conclusion, our results demonstrate that binding of the viral envelope to a specific HS configuration represents an important step for the initiation of viral infection and is a target of antiviral host immune responses in vivo. Mapping of viral and cellular determinants of HCV-HS interaction sets the stage for the development of novel HS-based antiviral strategies targeting viral attachment and entry. PMID:16928753

Expanding the role of 3-O sulfated heparan sulfate in herpes simplex virus type-1 entry

DOE Office of Scientific and Technical Information (OSTI.GOV)

O'Donnell, Christopher D., E-mail: codonn3@uic.ed; Department of Microbiology and Immunology, College of Medicine, University of Illinois at Chicago, Chicago, IL 60612; Kovacs, Maria, E-mail: marcsika101@yahoo.co

2010-02-20

Heparan sulfate (HS) proteoglycans are commonly exploited by multiple viruses for initial attachment to host cells. Herpes simplex virus-1 (HSV-1) is unique because it can use HS for both attachment and penetration, provided specific binding sites for HSV-1 envelope glycoprotein gD are present. The interaction with gD is mediated by specific HS moieties or 3-O sulfated HS (3-OS HS), which are generated by all but one of the seven isoforms of 3-O sulfotransferases (3-OSTs). Here we demonstrate that several common experimental cell lines express unique sets of 3-OST isoforms. While the isoforms 3-OST-3, -5 and -6 were most commonly expressed,more » isoforms 3-OST-2 and -4 were undetectable in the cell lines examined. Since most cell lines expressed multiple 3-OST isoforms, we addressed the significance of 3-OS HS in HSV-1 entry by down-regulating 2-O-sulfation, a prerequisite for 3-OS HS formation, by knocking down 2-OST expression by RNA interference (RNAi). 2-OST knockdown was verified by reverse-transcriptase PCR and Western blot analysis, while 3-OS HS knockdown was verified by immunofluorescence. Cells showed a significant decrease in viral entry, suggesting an important role for 3-OS HS. Implicating 3-OS HS further, cells knocked down for 2-OST expression also demonstrated decreased cell-cell fusion when cocultivated with effector cells transfected with HSV-1 glycoproteins. Our findings suggest that 3-OS HS may play an important role in HSV-1 entry into many different cell lines.« less

Effect of kefir and low-dose aspirin on arterial blood pressure measurements and renal apoptosis in unhypertensive rats with 4 weeks salt diet.

PubMed

Kanbak, Güngör; Uzuner, Kubilay; Kuşat Ol, Kevser; Oğlakçı, Ayşegül; Kartkaya, Kazım; Şentürk, Hakan

2014-01-01

Abstract We aim to study the effect of low-dose aspirin and kefir on arterial blood pressure measurements and renal apoptosis in unhypertensive rats with 4 weeks salt diet. Forty adult male Sprague-Dawley rats were divided into five groups: control, high-salt (HS) (8.0% NaCl), HS+aspirin (10 mg/kg), HS+kefir (10.0%w/v), HS+aspirin +kefir. We measured sistolic blood pressure (SBP), mean arterial pressure (MAP), diastolic pressure, pulse pressure in the rats. Cathepsin B, L, DNA fragmentation and caspase-3 activities were determined from rat kidney tissues and rats clearance of creatinine calculated. Although HS diet increased significantly SBP, MAP, diastolic pressure, pulse pressure parameters compared the control values. They were not as high as accepted hypertension levels. When compared to HS groups, kefir groups significantly decrease Cathepsin B and DNA fragmentation levels. Caspase levels were elevated slightly in other groups according to control group. While, we also found that creatinine clearance was higher in HS+kefir and HS+low-dose aspirin than HS group. Thus, using low-dose aspirin had been approximately decreased of renal function damage. Kefir decreased renal function damage playing as Angiotensin-converting enzyme inhibitor. But, low-dose aspirin together with kefir worsened rat renal function damage. Cathepsin B might play role both apoptosis and prorenin-processing enzyme. But not caspase pathway may be involved in the present HS diet induced apoptosis. In conclusion, kefir and low-dose aspirin used independently protect renal function and renal damage induced by HS diet in rats.

High salt intake shifts the mechanisms of flow-induced dilation in the middle cerebral arteries of Sprague-Dawley rats.

PubMed

Matic, Anita; Jukic, Ivana; Stupin, Ana; Baric, Lidija; Mihaljevic, Zrinka; Unfirer, Sanela; Tartaro Bujak, Ivana; Mihaljevic, Branka; Lombard, Julian H; Drenjancevic, Ines

2018-06-15

The goal of this study was to examine the effect of 1-week of high salt (HS) intake and the role of oxidative stress in changing the mechanisms of flow-induced dilation (FID) in isolated pressurized middle cerebral arteries (MCA) of male Sprague-Dawley rats (N=15-16/per group). Reduced FID in the HS group was restored by intake of the superoxide scavenger TEMPOL (HS+TEMPOL in vivo group). Nitric oxide synthases (NOS) inhibitor N ω -nitro-L-arginine methyl ester (L-NAME), COX inhibitor indomethacin (INDO) and selective inhibitor of microsomal CYP450 epoxidase activity N-(methylsulfonyl)-2-(2-propynyloxy)-benzenehexanamide (MS-PPOH) significantly reduced FID in the LS group, while FID in the HS group was mediated by NO only. COX-2 mRNA (but not protein) expression was decreased in the HS and HS+TEMPOL in vivo groups. HIF-1α and VEGF protein levels were increased in the HS group but decreased in the HS+TEMPOL in vivo group. Assessment by direct fluorescence of MCA under flow revealed significantly reduced vascular NO levels and increased superoxide/reactive oxygen species levels in the HS group. These results suggest that HS intake impairs FID and changes FID mechanisms to entirely NO-dependent, in contrast to the LS group where FID is NO, prostanoid and epoxyeicosatrienoic acids (EET's) dependent. Those changes were accompanied by increased lipid peroxidation products in the plasma of HS-fed rats, increased vascular superoxide/reactive oxygen species levels and decreased NO levels; together with increased expression of HIF-1α and VEGF.

Long-term seizure outcome for international consensus classification of hippocampal sclerosis: a survival analysis.

PubMed

Na, Meng; Ge, Haitao; Shi, Chen; Shen, Hong; Wang, Yu; Pu, Song; Liu, Li; Wang, Haiyang; Xie, Chuncheng; Zhu, Minwei; Wang, Jiabin; Shi, Changbin; Lin, Zhiguo

2015-02-01

Surgery is regarded as a common treatment option for patients with mesial temporal lobe epilepsy (MTLE) as a result of hippocampal sclerosis (HS). However, approximately one-third of patients with intractable epilepsy did not become seizure-free after tailored resection strategies. It would be compelling to identify predictive factors of postoperative seizure outcomes. Our aim was to assess the correlation between HS classification and long-term postoperative seizure outcome in patients with MTLE due to HS. To investigate HS classification, semi-quantitative analysis and immunohistochemical staining of neuronal nuclei (NeuN) were performed on 100 postoperative hippocampal specimens. All patients had a 1-7 year postoperative follow-up. The postoperative seizure outcome was evaluated using International League Against Epilepsy (ILAE) outcome classification. Three types of HS were recognized. The highest incidence of initial precipitating injury (IPI) was noted in the HS ILAE type 1 group (53.1%). The most favorable long-term seizure outcome was also noted in the HS ILAE type 1 group. The shortest epilepsy duration was recorded in the HS ILAE type 2 group (mean epilepsy duration=6.64 ± 5.83 years). The completely seizure free rate of patients in all groups declined with an increase in time. Our study for the first time demonstrated a significant correlation between HS ILAE types and long-term postoperative seizure outcome in patients with MTLE due to HS. Therefore, HS ILAE types have predictive value in long-term seizure outcome following epilepsy surgery. Copyright © 2014 British Epilepsy Association. Published by Elsevier Ltd. All rights reserved.

Derivatizing weak polyelectrolytes--solution properties, self-aggregation, and association with anionic surfaces of hydrophobically modified poly(ethylene imine).

PubMed

Griffiths, Peter C; Paul, Alison; Fallis, Ian A; Wellappili, Champa; Murphy, Damien M; Jenkins, Robert; Waters, Sarah J; Nilmini, Renuka; Heenan, Richard K; King, Stephen M

2007-10-15

The physical properties of weak polyelectrolytes may be tailored via hydrophobic modification to exhibit useful properties under appropriate pH and ionic strength conditions as a consequence of the often inherently competing effects of electrostatics and hydrophobicity. Pulsed-gradient spin-echo NMR (PGSE-NMR), electron paramagnetic resonance (EPR), small-angle neutron scattering (SANS) surface tension, fluorescence, and pH titration have been used to examine the solution conformation and aggregation behavior of a series of hydrophobically modified hyperbranched poly(ethylene imine) (PEI) polymers in aqueous solution, and their interaction with sodium dodecylsulfate (SDS). PGSE-NMR gave a particularly insightful picture of the apparent molecular weight distribution. The presence of the hydrophobes led to a lower effective charge on the polymer at any given pH, compared to the (parent) nonmodified samples. Analysis of the SANS data showed that the propensity to form highly elliptical or rod-like aggregates at higher pHs, reflecting both the changes in protonation behavior induced by the hydrophobic modification and an hydrophobic interaction, but that these structures were disrupted with decreasing pH (increasing charge). The parent samples were not surface active yet the hydrophobically modified samples show pronounced surface activity and the presence of small hydrophobic domains. The surface activity increased with an increase in the degree of modification. On addition of SDS, the onset of the formation of polymer/surfactant complexes was insensitive to the degree of modification with the resultant PEI/SDS complexes resembling the size and shape of simple SDS micelles. Indeed, the presence of the SDS effectively nullifies the effects of the hydrophobe. Hydrophobic modification is therefore a viable option to tailor pH dependent properties, whose effects may be removed by the presence of surfactant.

Passive Heating Attenuates Post-exercise Cardiac Autonomic Recovery in Healthy Young Males.

PubMed

Peçanha, Tiago; Forjaz, Cláudia L de Moraes; Low, David A

2017-01-01

Post-exercise heart rate (HR) recovery (HRR) presents a biphasic pattern, which is mediated by parasympathetic reactivation and sympathetic withdrawal. Several mechanisms regulate these post-exercise autonomic responses and thermoregulation has been proposed to play an important role. The aim of this study was to test the effects of heat stress on HRR and HR variability (HRV) after aerobic exercise in healthy subjects. Twelve healthy males (25 ± 1 years, 23.8 ± 0.5 kg/m 2 ) performed 14 min of moderate-intensity cycling exercise (40-60% HR reserve ) followed by 5 min of loadless active recovery in two conditions: heat stress (HS) and normothermia (NT). In HS, subjects dressed in a whole-body water-perfused tube-lined suit to increase internal temperature (T c ) by ~1°C. In NT, subjects did not wear the suit. HR, core and skin temperatures (T c and T sk ), mean arterial pressure (MAP) skin blood flow (SKBF), and cutaneous vascular conductance (CVC) were measured throughout and analyzed during post-exercise recovery. HRR was assessed through calculations of HR decay after 60 and 300 s of recovery (HRR60s and HRR300s), and the short- and long-term time constants of HRR (T30 and HRRt). Post-exercise HRV was examined via calculations of RMSSD (root mean square of successive RR intervals) and RMS (root mean square residual of RR intervals). The HS protocol promoted significant thermal stress and hemodynamic adjustments during the recovery (HS-NT differences: T c = +0.7 ± 0.3°C; T sk = +3.2 ± 1.5°C; MAP = -12 ± 14 mmHg; SKBF = +90 ± 80 a.u; CVC = +1.5 ± 1.3 a.u./mmHg). HRR and post-exercise HRV were significantly delayed in HS (e.g., HRR60s = 27 ± 9 vs. 44 ± 12 bpm, P < 0.01; HRR300s = 39 ± 12 vs. 59 ± 16 bpm, P < 0.01). The effects of heat stress (e.g., the HS-NT differences) on HRR were associated with its effects on thermal and hemodynamic responses. In conclusion, heat stress delays HRR, and this effect seems to be mediated by an attenuated parasympathetic reactivation and sympathetic withdrawal after exercise. In addition, the impact of heat stress on HRR is related to the magnitude of the heat stress-induced thermal stress and hemodynamic changes.

Rapid identification of pork for halal authentication using the electronic nose and gas chromatography mass spectrometer with headspace analyzer.

PubMed

Nurjuliana, M; Che Man, Y B; Mat Hashim, D; Mohamed, A K S

2011-08-01

The volatile compounds of pork, other meats and meat products were studied using an electronic nose and gas chromatography mass spectrometer with headspace analyzer (GCMS-HS) for halal verification. The zNose™ was successfully employed for identification and differentiation of pork and pork sausages from beef, mutton and chicken meats and sausages which were achieved using a visual odor pattern called VaporPrint™, derived from the frequency of the surface acoustic wave (SAW) detector of the electronic nose. GCMS-HS was employed to separate and analyze the headspace gasses from samples into peaks corresponding to individual compounds for the purpose of identification. Principal component analysis (PCA) was applied for data interpretation. Analysis by PCA was able to cluster and discriminate pork from other types of meats and sausages. It was shown that PCA could provide a good separation of the samples with 67% of the total variance accounted by PC1. Copyright © 2011 Elsevier Ltd. All rights reserved.

Slightly elevated high-sensitivity C-reactive protein (hsCRP) concentrations are associated with carotid atherosclerosis in women with varying degrees of glucose tolerance.

PubMed

Prahl, Ulrica; Wikstrand, John; Bergström, Göran M L; Behre, Carl Johan; Hulthe, Johannes; Fagerberg, Björn

2010-11-01

We examined whether high-sensitivity C-reactive protein (hsCRP) ≥2.0 mg/L was associated with increased intima-media thickness (IMT), plaque burden, and plaque echolucency in carotid arteries. Women (n = 635) from a population sample of 64-year-old females with varying degrees of glucose tolerance underwent risk factor assessment, measurement of hsCRP, and ultrasound examinations of the carotid arteries. Participants with hsCRP levels ≥2.0 mg/L had elevated carotid bulb IMT independently of other cardiovascular risk factors compared with those with hsCRP <2.0 mg/L. The participants with plaques in the highhsCRP group had larger total plaque area compared to those with plaque in the lower hsCRP group. Plaque echolucency did not differ between groups. High-sensitivity CRP levels ≥2.0 mg/L were accompanied by elevated IMT in the carotid bulbs independently of other cardiovascular risk factors. Total plaque area was larger among women with plaques in the high hsCRP group versus the lower hsCRP group.

Photoreduction of Terrigenous Fe-Humic Substances Leads to Bioavailable Iron in Oceans.

PubMed

Blazevic, Amir; Orlowska, Ewelina; Kandioller, Wolfgang; Jirsa, Franz; Keppler, Bernhard K; Tafili-Kryeziu, Myrvete; Linert, Wolfgang; Krachler, Rudolf F; Krachler, Regina; Rompel, Annette

2016-05-23

Humic substances (HS) are important iron chelators responsible for the transport of iron from freshwater systems to the open sea, where iron is essential for marine organisms. Evidence suggests that iron complexed to HS comprises the bulk of the iron ligand pool in near-coastal waters and shelf seas. River-derived HS have been investigated to study their transport to, and dwell in oceanic waters. A library of iron model compounds and river-derived Fe-HS samples were probed in a combined X-ray absorption spectroscopy (XAS) and valence-to-core X-ray emission spectroscopy (VtC-XES) study at the Fe K-edge. The analyses performed revealed that iron complexation in HS samples is only dependent on oxygen-containing HS functional groups, such as carboxyl and phenol. The photoreduction mechanism of Fe III -HS in oceanic conditions into bioavailable aquatic Fe II forms, highlights the importance of river-derived HS as an iron source for marine organisms. Consequently, such mechanisms are a vital component of the upper-ocean iron biogeochemistry cycle.

Development and characterization of edible films based on mucilage of Opuntia ficus-indica (L.).

PubMed

Espino-Díaz, Miguel; de Jesús Ornelas-Paz, J; Martínez-Téllez, Miguel A; Santillán, Carlos; Barbosa-Cánovas, Gustavo V; Zamudio-Flores, Paul B; Olivas, Guadalupe I

2010-08-01

Mucilage of Opuntia ficus-indica (OFI) was extracted and characterized by its composition and molecular weight distribution. Mucilage film-forming dispersions were prepared under different pHs (3, 4, 5.6, 7, and 8) and calcium concentration (0% and 30% of CaCl(2), with respect to mucilage's weight), and their particle size determined. Mucilage films with and without calcium (MFCa and MF, respectively) were prepared. The effect of calcium and pH on mucilage films was evaluated determining thickness, color, water vapor permeability (WVP), tensile strength (TS), and percentage of elongation (%E). The average molecular weight of the different fractions of mucilage was: 3.4 x 10(6) (0.73%), 1 x 10(5) (1.46%), 1.1 x 10(3) (45.79%), and 2.4 x 10(2) Da (52.03%). Aqueous mucilage dispersions with no calcium presented particles with an average size d(0.5) of 15.4 microm, greater than the dispersions with calcium, 13.2 microm. MFCa films showed more thickness (0.13 mm) than the MF films (0.10 mm). The addition of calcium increased the WVP of the films from 109.94 to 130.45 gmm/m(2)dkPa. Calcium and pH affected the mechanical properties of the films; the largest TS was observed on MF films, whereas the highest %E was observed on MFCa films. The highest differences among MF and MFCa films were observed at pHs 5.6 and 7 for TS and at pHs 4 and 8 for %E. No effect of pH and calcium was observed on luminosity and hue angle. Chroma values were higher for MF when compared with MFCa, and increased as pH of the films increased. Practical Application: In this study mucilage from nopal was extracted and characterized by its ability to form edible films under different pHs, and with or without the addition of calcium. Opuntia ficus-indica mucilage had the ability to form edible films. In general, it can be considered that mucilage films without modification of pH and without the addition of calcium have the best water vapor barrier properties and tensile strength. Mucilage from nopal could represent a good option for the development of edible films in countries where nopal is highly produced at low cost, constituting a processing alternative for nopal.

The role of n terminal - probrain natriuretic peptide in the diagnosis of hemodynamic persistent asrteriosus ductus in premature neonates patient

NASA Astrophysics Data System (ADS)

Dasraf, D.; Djer, M. M.; Advani, N.

2017-08-01

Persistent ductus arteriosus is one of the most frequent congenital heart diseases found in infants, mainly in preterms. Echocardiography is the gold standard for the diagnosis of hemodynamically significant patent ductus arteriosus (hs-PDA) in preterm neonates. A few studies have suggested that the use of a simple blood assay to detect N-terminal pro-brain natriuretic peptide (NT-proBNP) may be useful in determining the diagnosis and management of hs-PDA. No such studies have been conducted in Indonesia, although the assay kit and characteristics of the patient (gestational age and chronological age) influence the accuracy of NT-proBNP levels in determining hs-PDA. The aim of this study was to determine the association between the NT-proBNP level and the prevalence of hs-PDA in an Indonesian patient population. A cross-sectional study was conducted at Dr. Cipto Mangunkusumo Hospital. PDA was determined using echocardiography in 49 preterm neonates (gestational age <37 weeks and birthweight <2000 g). Subsequently, these patients were divided into three groups: non-PDA, non-hsPDA, and hs-PDA. The blood NT-proBNP level was then determined in the non-hsPDA and hs-PDA groups, and between-group differences were compared. Among the 49 neonates, 33 patients had PDA, and 16 of these had hs-PDA. The results revealed a significant association between the NT-proBNP level and hs-PDA (p < 0.001).

Effects of humic substances on the bioconcentration of polycyclic aromatic hydrocarbons: Correlations with spectroscopic and chemical properties of humic substances

USGS Publications Warehouse

Haitzer, M.; Abbt-Braun, G.; Traunspurger, W.; Steinberg, C.E.W.

1999-01-01

The presence of dissolved humic substances (HS, fulvic and humic acids) generally reduces the uptake of hydrophobic organic compounds into aquatic organisms. The extent of this effect depends both on the concentration and on the origin of the HS. The aim of this study was to investigate the role of qualitative differences between HS from different origins. The effects of seven different HS on the bioconcentration of pyrene and benzo[a]pyrene (BaP) in the nematode Caenorhabditis elegans were related to the spectroscopic and chemical properties of the HS. The effect of each humic material on the bioconcentration of pyrene or BaP was quantified as a 'biologically determined' partition coefficient K(DOC). We observed significant linear relationships between K(DOC) and the atomic H/C ratio, the specific absorptivity at 254 nm, the content of aromatic carbons (as determined by 13C nuclear magnetic resonance spectroscopy, the copper-complexing capacity, the content of phenolic OH groups, and the molecular weight of the HS. There was no discernible relationship of K(DOC) with the atomic (N + O)/C ratio, an indicator of the polarity of HS. Taken together, our results show that the variability in the effects of HS from different origins could be related to variations in bulk properties of the HS. Parameters describing the aromaticity of the humic materials seemed to be most useful for estimating effects of HS on the bioconcentration of pyrene and BaP.

ChromBiSim: Interactive chromatin biclustering using a simple approach.

PubMed

Noureen, Nighat; Zohaib, Hafiz Muhammad; Qadir, Muhammad Abdul; Fazal, Sahar

2017-10-01

Combinatorial patterns of histone modifications sketch the epigenomic locale. Specific positions of these modifications in the genome are marked by the presence of such signals. Various methods highlight such patterns on global scale hence missing the local patterns which are the actual hidden combinatorics. We present ChromBiSim, an interactive tool for mining subsets of modifications from epigenomic profiles. ChromBiSim efficiently extracts biclusters with their genomic locations. It is the very first user interface based and multiple cell type handling tool for decoding the interplay of subsets of histone modifications combinations along their genomic locations. It displays the results in the forms of charts and heat maps in accordance with saving them in files which could be used for post analysis. ChromBiSim tested on multiple cell types produced in total 803 combinatorial patterns. It could be used to highlight variations among diseased versus normal cell types of any species. ChromBiSim is available at (http://sourceforge.net/projects/chrombisim) in C-sharp and python languages. Copyright © 2017 Elsevier Inc. All rights reserved.

Strengthening the Healthy Start Workforce: A Mixed-Methods Study to Understand the Roles of Community Health Workers in Healthy Start and Inform the Development of a Standardized Training Program.

PubMed

DeAngelis, Katherine Rachel; Doré, Katelyn Flaherty; Dean, Deborah; Osterman, Paul

2017-12-01

Introduction Healthy Start (HS) is dedicated to preventing infant mortality, improving birth outcomes, and reducing disparities in maternal and infant health. In 2014, the HS program was reenvisioned and standardization of services and workforce development were prioritized. This study examined how HS community health workers (CHW), as critical members of the workforce, serve families and communities in order to inform the development of a CHW training program to advance program goals. Methods In 2015, an online organizational survey of all 100 HS programs was conducted. Ninety-three sites (93%) responded. Three discussion groups were subsequently conducted with HS CHWs (n = 21) and two discussion groups with HS CHW trainers/supervisors (n = 14). Results Most (91%) respondent HS programs employed CHWs. Survey respondents ranked health education (90%), assessing participant needs (85%), outreach/recruitment (85%), and connecting participants to services (85%) as the most central roles to the CHW's job. Survey findings indicated large variation in CHW training, both in the amount and content provided. Discussion group findings provided further examples of the knowledge and skills required by HS CHWs. Conclusions The study results, combined with a scan of existing competencies, led to a tailored set of competencies that serve as the foundation for a HS CHW training program. This training program has the capacity to advance strategic goals for HS by strengthening HS CHWs' capacity nationwide to respond to complex participant needs. Other maternal and child health programs may find these results of interest as they consider how CHWs could be used to strengthen service delivery.

Selective κ receptor partial agonist HS666 produces potent antinociception without inducing aversion after i.c.v. administration in mice.

PubMed

Spetea, Mariana; Eans, Shainnel O; Ganno, Michelle L; Lantero, Aquilino; Mairegger, Michael; Toll, Lawrence; Schmidhammer, Helmut; McLaughlin, Jay P

2017-08-01

The κ receptor has a central role in modulating neurotransmission in central and peripheral neuronal circuits that subserve pain and other behavioural responses. Although κ receptor agonists do not produce euphoria or lead to respiratory suppression, they induce dysphoria and sedation. We hypothesized that brain-penetrant κ receptor ligands possessing biased agonism towards G protein signalling over β-arrestin2 recruitment would produce robust antinociception with fewer associated liabilities. Two new diphenethylamines with high κ receptor selectivity, HS665 and HS666, were assessed following i.c.v. administration in mouse assays of antinociception with the 55°C warm-water tail withdrawal test, locomotor activity in the rotorod and conditioned place preference. The [ 35 S]-GTPγS binding and β-arrestin2 recruitment in vitro assays were used to characterize biased agonism. HS665 (κ receptor agonist) and HS666 (κ receptor partial agonist) demonstrated dose-dependent antinociception after i.c.v. administration mediated by the κ receptor. These highly selective κ receptor ligands displayed varying biased signalling towards G protein coupling in vitro, consistent with a reduced liability profile, reflected by reduced sedation and absence of conditioned place aversion for HS666. HS665 and HS666 activate central κ receptors to produce potent antinociception, with HS666 displaying pharmacological characteristics of a κ receptor analgesic with reduced liability for aversive effects correlating with its low efficacy in the β-arrestin2 signalling pathway. Our data provide further understanding of the contribution of central κ receptors in pain suppression, and the prospect of dissociating the antinociceptive effects of HS665 and HS666 from κ receptor-mediated adverse effects. © 2017 The Authors. British Journal of Pharmacology published by John Wiley & Sons Ltd on behalf of British Pharmacological Society.

Comparison of Cognitive Parameters Between Bilateral and Unilateral Hippocampal Sclerosis.

PubMed

Vanli Yavuz, Ebru Nur; Bilgiç, Başar; Matur, Zeliha; Bebek, Nerses; Gürses, Candan; Gökyiğit, Ayşen; Öktem, Öget; Baykan, Betül

2016-09-01

Recent studies showed that hippocampal sclerosis (HS) patients with unilateral involvement had more diffuse cognitive impairment than expected. Therefore, we aimed to compare the cognitive profiles of bilateral HS (BHS) patients with unilateral HS (UHS) patients. Consecutive patients, diagnosed with epilepsy, who fulfilled two major magnetic resonance imaging (MRI) criteria (T1 atrophy and T2-FLAIR hyperintensity) for HS were included. Standard neuro-psychological test (NPT) battery consisted of the Turkish version of 15-word verbal memory processes test, Wechsler memory scale visual reproduction subtest, forward and backward digit span, phonemic and semantic fluency, and Stroop test were applied; and the groups with right HS, left HS, and bilateral HS were compared statistically. Ninety-one patients, completing the NPT (34 males, 57 females)-16 with BHS, 36 with right HS, and 39 with left HS-were included. Six out of 43 operated patients had BHS. There were no significant differences in education and handedness of the groups. Even though NPT performances of the BHS group were found to be poor compared to UHS subgroups, this was beyond statistical significance. Comparison of BHS with the right HS group showed a significant difference in the learning score of the Verbal Memory Processes Test, but recognition scores were found to be similar in all groups. Compared to the BHS group, both right and left HS groups revealed a significant difference in delayed recall score of the Verbal Memory Processes Test. Although there were no significant differences in the postoperative parameters of the BHS group, UHS subgroups had deficits in many postoperative parameters. Our study revealed that bilateral involvement of the hippocampi was correlated with a poor cognitive performance. Retrieval failure, rather than a total recall problem, in the memory of the patients resembles a more diffuse involvement not only limited to limbic structures.

Effects of cyclic heat stress or vitamin C supplementation during cyclic heat stress on HSP70, inflammatory cytokines, and the antioxidant defense system in Sprague Dawley rats.

PubMed

Yun, Seo-Hyun; Moon, Yang-Soo; Sohn, Sea-Hwan; Jang, In-Surk

2012-01-01

A total of 21 male SD rats were divided into three groups to investigate the effects of consecutive cyclic heat stress or vitamin C under heat stress on heat shock protein (HSP) 70, inflammatory cytokines, and antioxidant systems. The heat stress (HS) and vitamin C supplementation during heat stress (HS+VC) groups were exposed to cyclic heat stress (23 to 38 to 23°C) for 2 h on each of seven consecutive days. The HS+VC group had free access to water containing 0.5% vitamin C throughout the experiment. Hepatic HSP70 mRNA in the HS group was significantly (P<0.05) higher than that in the control (CON) or HS+VC group. The mRNA levels of tumor necrosis factor (TNF)-α and inducible nitric oxide synthase (iNOS) in the HS group were greater (P<0.05) than those in the CON group. The HS+VC group showed significantly (P<0.05) lower mRNA levels of hepatic interleukin-6 and TNF-α than the HS group. However, thymic HSP70 and inflammatory cytokines were unaffected by treatments. In the hepatic antioxidant system, the mRNA and activity of glutathione peroxidase (GPX) were greater (P<0.05) in the HS than in the CON group, whereas the HS+VC group showed markedly (P<0.05) lower GPX mRNA and activity than the HS group. However, superoxide dismutase, glutathione S-transferase, and malondialdehyde were unaffected by treatments. In conclusion, cyclic heat stress activated hepatic HSP70, TNF-α, iNOS, and GPX genes, whereas vitamin C during heat stress ameliorated heat stress-induced cellular responses in rats.

Hemistepsin A ameliorates acute inflammation in macrophages via inhibition of nuclear factor-κB and activation of nuclear factor erythroid 2-related factor 2.

PubMed

Kim, Jae Kwang; Lee, Ji Eun; Jung, Eun Hye; Jung, Ji Yun; Jung, Dae Hwa; Ku, Sae Kwang; Cho, Il Je; Kim, Sang Chan

2018-01-01

Hemistepsin A (HsA) is a sesquiterpene lactone isolated from Hemistepta lyrata (Bunge) Bunge. We investigated the anti-inflammatory effects of HsA and sought to determine its mechanisms of action in macrophages. HsA pretreatment inhibited nitric oxide production, and reduced the expression of iNOS and COX-2 in Toll-like receptor ligand-stimulated RAW 264.7 cells. Additionally, HsA decreased the secretion of proinflammatory cytokines in lipopolysaccharide (LPS)-stimulated Kupffer cells as well as in RAW 264.7 cells. HsA inhibited phosphorylation of IKKα/β and degradation of IκBα, resulting in decreased nuclear translocation of nuclear factor-κB (NF-κB) and its transcriptional activity. Moreover, HsA phosphorylated nuclear factor erythroid 2-related factor 2 (Nrf2), increased expression levels of antioxidant genes, and attenuated LPS-stimulated H 2 O 2 production. Phosphorylation of p38 and c-Jun N-terminal kinase was required for HsA-mediated Nrf2 phosphorylation. In a D-galactosamine/LPS-induced liver injury model, HsA ameliorated D-galactosamine/LPS-induced hepatocyte degeneration and inflammatory cells infiltration. Moreover, immunohistochemical analyses using nitrotyrosine, 4-hydroxynonenal, and cleaved poly (ADP-ribose) polymerase antibodies revealed that HsA protected the liver from oxidative stress. Furthermore, HsA reduced the numbers of proinflammatory cytokine-positive cells in hepatic tissues. Thus, these results suggest HsA may be a promising natural product to manage inflammation-mediated tissue injuries through inhibition of NF-κB and activation of Nrf2. Copyright © 2017 Elsevier Ltd. All rights reserved.

High-Sensitivity Troponin: A Clinical Blood Biomarker for Staging Cardiomyopathy in Fabry Disease.

PubMed

Seydelmann, Nora; Liu, Dan; Krämer, Johannes; Drechsler, Christiane; Hu, Kai; Nordbeck, Peter; Schneider, Andreas; Störk, Stefan; Bijnens, Bart; Ertl, Georg; Wanner, Christoph; Weidemann, Frank

2016-05-31

High-sensitivity troponin (hs-TNT), a biomarker of myocardial damage, might be useful for assessing fibrosis in Fabry cardiomyopathy. We performed a prospective analysis of hs-TNT as a biomarker for myocardial changes in Fabry patients and a retrospective longitudinal follow-up study to assess longitudinal hs-TNT changes relative to fibrosis and cardiomyopathy progression. For the prospective analysis, hs-TNT from 75 consecutive patients with genetically confirmed Fabry disease was analyzed relative to typical Fabry-associated echocardiographic findings and total myocardial fibrosis as measured by late gadolinium enhancement (LE) on magnetic resonance imaging. Longitudinal data (3.9±2.0 years), including hs-TNT, LE, and echocardiographic findings from 58 Fabry patients, were retrospectively collected. Hs-TNT level positively correlated with LE (linear correlation coefficient, 0.72; odds ratio, 32.81 [95% CI, 3.56-302.59]; P=0.002); patients with elevated baseline hs-TNT (>14 ng/L) showed significantly increased LE (median: baseline, 1.9 [1.1-3.3] %; follow-up, 3.2 [2.3-4.9] %; P<0.001) and slightly elevated hs-TNT (baseline, 44.7 [30.1-65.3] ng/L; follow-up, 49.1 [27.6-69.5] ng/L; P=0.116) during follow-up. Left ventricular wall thickness and EF of patients with elevated hs-TNT were decreased during follow-up, indicating potential cardiomyopathy progression. hs-TNT is an accurate, easily accessible clinical blood biomarker for detecting replacement fibrosis in patients with Fabry disease and a qualified predictor of cardiomyopathy progression. Thus, hs-TNT could be helpful for staging and follow-up of Fabry patients. © 2016 The Authors. Published on behalf of the American Heart Association, Inc., by Wiley Blackwell.

Temporal lobe volumes in patients with hippocampal sclerosis with or without cortical dysplasia.

PubMed

Diehl, B; Najm, I; LaPresto, E; Prayson, R; Ruggieri, P; Mohamed, A; Ying, Z; Lieber, M; Babb, T; Bingaman, W; Lüders, H O

2004-05-25

Recent MRI-based volume reconstruction studies in intractable temporal lobe epilepsy (TLE) due to hippocampal sclerosis (HS) suggested atrophy that extends to the adjacent neocortical areas. To study the extent of temporal lobe volume (TLV) abnormalities in patients with pathologically confirmed HS (with or without cortical dysplasia [CD]) who underwent anterior temporal lobectomy for the treatment of drug-resistant TLE. Fifty patients (right TLE: n = 24; left TLE: n = 26) were found to have HS (hippocampal cell loss of >30%). Associated neocortical CD was seen in 20 patients (43%). MRI-based TLVs and hippocampal and hemispheric volume reconstructions in all patients were compared between pathologic groups and with volumes acquired from 10 age-matched control subjects. TLVs ipsilateral to the epileptogenic zone in patients with TLE were smaller than TLVs in control subjects (p < 0.01). In patients with left TLE, TLVs ipsilateral to the epileptogenic zone were smaller than contralateral TLVs (left: 66.6 +/- 8.3 cm3, right: 74.9 +/- 10.0 cm3; p < 0.001). In patients with right TLE, there were no significant asymmetries. The contralateral TLVs (regardless of the side of surgery) were smaller in the HS + CD group than the HS group (HS + CD group: 74.9 +/- 8.6 cm3, HS group: 79.7 +/- 6.6 cm3; p < 0.05). Patients with HS + CD had a tendency to have less hippocampal atrophy and slightly smaller TLVs ipsilateral to the epileptogenic zone, accounting for significantly smaller TLV/hippocampal volume ratios compared with patients with HS alone. Drug-resistant TLE due to HS is associated with extrahippocampal temporal lobe atrophy. The presence of bilateral temporal lobe atrophy is suggestive of a more widespread (bilateral) temporal lobe involvement in patients with HS and CD.

Prognostic Value of High-Sensitivity C-Reactive Protein, Procalcitonin and Pancreatic Stone Protein in Pediatric Sepsis.

PubMed

Wu, Qiong; Nie, Jun; Wu, Fu-Xia; Zou, Xiu-Lan; Chen, Feng-Yi

2017-03-30

BACKGROUND To investigate the prognostic value of procalcitonin (PCT), high-sensitivity C-reactive protein (hs-CRP), and pancreatic stone protein (PSP) in children with sepsis. MATERIAL AND METHODS A total of 214 patients with sepsis during hospitalization were enrolled. Serum levels of PCT, hs-CRP, and PSP were measured on day 1 of hospitalization and the survival rates of children were recorded after a follow-up of 28 days. Pearson's correlation analysis was conducted to test the association of PCT, hs-CRP, and PSP with pediatric critical illness score (PCIS). Logistic regression models were used to analyze the risk factors contributing to patients' death. The AUC was used to determine the value of PCT, hs-CRP, and PSP in the prognosis of patients with sepsis. RESULTS The expression of PCT, hs-CRP, and PSP in the dying patients was higher than in the surviving patients (p<0.001). Pearson's correlation analysis showed that serum PCT, hs-CRP, and PSP levels were negatively correlated with PCIS (p<0.001). Multivariate logistic regression revealed that PCT, hs-CRP, and PSP were independent risk factors for the prognosis of patients with sepsis (p<0.001). ROC analysis showed the AUC values of PCT, hs-CRP, and PSP were 0.83 (95% CI, 0.77-0.88), 0.76 (95% CI, 0.70-0.82), and 0.73 (95% CI, 0.67-0.79), respectively. The combined AUC value of PCT, hs-CRP, and PSP, was 0.92 (95% CI, 0.87-0.95), which was significantly increased compared with PCT, hs-CRP, or PSP (p<0.001). CONCLUSIONS The combination of serum PCT, hs-CRP, and PSP represents a promising biomarker of risk, and is a useful clinical tool for risk stratification of children with sepsis.

GlycA and hsCRP are independent and additive predictors of future cardiovascular events among patients undergoing angiography: The intermountain heart collaborative study.

PubMed

Muhlestein, Joseph B; May, Heidi T; Galenko, Oxana; Knowlton, Kirk U; Otvos, James D; Connelly, Margery A; Lappe, Donald L; Anderson, Jeffrey L

2018-04-06

GlycA is an inflammatory marker that is raised in patients with cardiometabolic diseases and associated with cardiovascular (CV) events. We sought to determine if GlycA adds independent value to hsCRP for CV risk prediction. Patients in the Intermountain Heart Collaborative Study who underwent coronary angiography and had plasma GlycA and hsCRP levels were studied (n = 2996). Patients were followed for 7.0 ± 2.8 years. GlycA and hsCRP were moderately correlated (r = 0.46, P < .0001). GlycA and hsCRP concentrations were stratified into high and low categories by their median values. Multivariable cox hazard regression was utilized to determine the associations of GlycA quartiles, as well as high and low categories of GlycA and hsCRP, with major adverse cardiovascular events (MACE) defined as the composite of death, myocardial infarction (MI), heart failure (HF) hospitalization, and stroke. The highest GlycA quartile was associated with future MACE [HR: 1.43; 95% CI: 1.22-1.69; P < .0001]. Patients with high GlycA and high hsCRP had more diabetes, hyperlipidemia, hypertension, HF, renal failure and MI, but not coronary artery disease. High GlycA and hsCRP (H/H) versus low GlycA and hsCRP (L/L) was associated with MACE, death and HF hospitalization, but not MI or stroke. Combined MACE rates were 33.5%, 41.3%, 35.7% and 49.1% for L/L, L/H, H/L and H/H categories of GlycA/hsCRP, respectively (P-trend < .0001). The interaction between GlycA and hsCRP was significant for the outcome of death (P = .03). In this study, levels of GlycA and hsCRP were independent and additive markers of risk for MACE, death and HF hospitalization. Copyright © 2018. Published by Elsevier Inc.

3-O-sulfated heparan sulfate recognized by the antibody HS4C3 contributes [corrected] to the differentiation of mouse embryonic stem cells via fas signaling.

PubMed

Hirano, Kazumi; Sasaki, Norihiko; Ichimiya, Tomomi; Miura, Taichi; Van Kuppevelt, Toin H; Nishihara, Shoko

2012-01-01

Maintenance of self-renewal and pluripotency in mouse embryonic stem cells (mESCs) is regulated by the balance between several extrinsic signaling pathways. Recently, we demonstrated that heparan sulfate (HS) chains play important roles in the maintenance and differentiation of mESCs by regulating extrinsic signaling. Sulfated HS structures are modified by various sulfotransferases during development. However, the significance of specific HS structures during development remains unclear. Here, we show that 3-O-sulfated HS structures synthesized by HS 3-O-sulfotransferases (3OSTs) and recognized by the antibody HS4C3 increase during differentiation of mESCs. Furthermore, expression of Fas on the cell surface of the differentiated cells also increased. Overexpression of the HS4C3-binding epitope in mESCs induced apoptosis and spontaneous differentiation even in the presence of LIF and serum. These data showed that the HS4C3-binding epitope was required for differentiation of mESCs. Up-regulation of the HS4C3-binding epitope resulted in the recruitment of Fas from the cytoplasm to lipid rafts on the cell surface followed by activation of Fas signaling. Indeed, the HS4C3-binding epitope interacted with a region that included the heparin-binding domain (KLRRRVH) of Fas. Reduced self-renewal capability in cells overexpressing 3OST resulted from the degradation of Nanog by activated caspase-3, which is downstream of Fas signaling, and was rescued by the inhibition of Fas signaling. We also found that knockdown of 3OST and inhibition of Fas signaling reduced the potential for differentiation into the three germ layers during embryoid body formation. This is the first demonstration that activation of Fas signaling is mediated by an increase in the HS4C3-binding epitope and indicates a novel signaling pathway for differentiation in mESCs.

3-O-Sulfated Heparan Sulfate Recognized by the Antibody HS4C3 Contribute to the Differentiation of Mouse Embryonic Stem Cells via Fas Signaling

PubMed Central

Hirano, Kazumi; Sasaki, Norihiko; Ichimiya, Tomomi; Miura, Taichi; Van Kuppevelt, Toin H.; Nishihara, Shoko

2012-01-01

Maintenance of self-renewal and pluripotency in mouse embryonic stem cells (mESCs) is regulated by the balance between several extrinsic signaling pathways. Recently, we demonstrated that heparan sulfate (HS) chains play important roles in the maintenance and differentiation of mESCs by regulating extrinsic signaling. Sulfated HS structures are modified by various sulfotransferases during development. However, the significance of specific HS structures during development remains unclear. Here, we show that 3-O-sulfated HS structures synthesized by HS 3-O-sulfotransferases (3OSTs) and recognized by the antibody HS4C3 increase during differentiation of mESCs. Furthermore, expression of Fas on the cell surface of the differentiated cells also increased. Overexpression of the HS4C3-binding epitope in mESCs induced apoptosis and spontaneous differentiation even in the presence of LIF and serum. These data showed that the HS4C3-binding epitope was required for differentiation of mESCs. Up-regulation of the HS4C3-binding epitope resulted in the recruitment of Fas from the cytoplasm to lipid rafts on the cell surface followed by activation of Fas signaling. Indeed, the HS4C3-binding epitope interacted with a region that included the heparin-binding domain (KLRRRVH) of Fas. Reduced self-renewal capability in cells overexpressing 3OST resulted from the degradation of Nanog by activated caspase-3, which is downstream of Fas signaling, and was rescued by the inhibition of Fas signaling. We also found that knockdown of 3OST and inhibition of Fas signaling reduced the potential for differentiation into the three germ layers during embryoid body formation. This is the first demonstration that activation of Fas signaling is mediated by an increase in the HS4C3-binding epitope and indicates a novel signaling pathway for differentiation in mESCs. PMID:22916262

High-sensitivity serum C-reactive protein levels in subjects with or without myocardial infarction or periodontitis.

PubMed

Persson, G Rutger; Pettersson, Thomas; Ohlsson, Ola; Renvert, Stefan

2005-03-01

Serum high-sensitivity C-reactive protein (hsC-rp) is a non-specific marker of inflammation. Elevated hsC-rp levels are found in subjects with cardiovascular diseases (CVDs). Periodontitis may influence hsC-rp levels. To assess periodontal status and hsC-rp serum levels in consecutive subjects hospitalized and diagnosed with acute myocardial infarction (AMI) (n=85) and in a group of carefully matched subjects (gender, age social, ethnic, and smoking habits) without clinical evidence of CVD (n=63). hsC-rp levels, other routine serum values, and clinical periodontal conditions were studied. Subjects with AMI had higher hsC-rp levels than control subjects (p<0.001, Mann-Whitney U-test). The odds that subjects in the control group with periodontitis (30% or more sites with>4.0 mm loss of alveolar bone) had serum hsC-rp>1.8 mg/l was 1.5 (95% CI: 1.1-7.3, p<0.05). Stepwise linear regression analysis failed to include periodontal parameters in an explanatory model to hsC-rp values. Only the serum leucocyte (white blood cell (WBC)) counts were explanatory to hsC-rp values (beta standard coefficient=0.45, t=3.2, p<0.001). Serum WBC counts were significantly higher in control subjects with periodontitis (p<0.03) but not in subjects in the AMI group (p<0.57). (1) As expected, elevated serum hsC-rp concentration and serum WBC counts are associated with acute coronary heart disease. (2) Elevated serum hsC-rp values are associated with radiographically defined periodontitis in subjects with no evidence of CVD. (3) Periodontal parameters are not explanatory to elevated serum hsC-rp values if serum WBC and low-density lipoprotein counts are included in the regression model. Copyright 2005 Blackwell Munksgaard.

Spatial learning in the genetically heterogeneous NIH-HS rat stock and RLA-I/RHA-I rats: revisiting the relationship with unconditioned and conditioned anxiety.

PubMed

Martínez-Membrives, Esther; López-Aumatell, Regina; Blázquez, Gloria; Cañete, Toni; Tobeña, Adolf; Fernández-Teruel, Alberto

2015-05-15

To characterize learning/memory profiles for the first time in the genetically heterogeneous NIH-HS rat stock, and to examine whether these are associated with anxiety, we evaluated NIH-HS rats for spatial learning/memory in the Morris water maze (MWM) and in the following anxiety/fear tests: the elevated zero-maze (ZM; unconditioned anxiety), a context-conditioned fear test and the acquisition of two-way active avoidance (conditioned anxiety). NIH-HS rats were compared with the Roman High- (RHA-I) and Low-Avoidance (RLA-I) rat strains, given the well-known differences between the Roman strains/lines in anxiety-related behavior and in spatial learning/memory. The results show that: (i) As expected, RLA-I rats were more anxious in the ZM test, displayed more frequent context-conditioned freezing episodes and fewer avoidances than RHA-I rats. (ii) Scores of NIH-HS rats in these tests/tasks mostly fell in between those of the Roman rat strains, and were usually closer to the values of the RLA-I strain. (iii) Pigmented NIH-HS (only a small part of NIH-HS rats were albino) rats were the best spatial learners and displayed better spatial memory than the other three (RHA-I, RLA-I and NIH-HS albino) groups. (iv) Albino NIH-HS and RLA-I rats also showed better learning/memory than the RHA-I strain. (v) Within the NIH-HS stock, the most anxious rats in the ZM test presented the best learning and/or memory efficiency (regardless of pigmentation). In summary, NIH-HS rats display a high performance in spatial learning/memory tasks and a passive coping strategy when facing conditioned conflict situations. In addition, unconditioned anxiety in NIH-HS rats predicts better spatial learning/memory. Copyright © 2015 Elsevier Inc. All rights reserved.

Hemorrhagic shock shifts the serum cytokine profile from pro- to anti-inflammatory after experimental traumatic brain injury in mice.

PubMed

Shein, Steven L; Shellington, David K; Exo, Jennifer L; Jackson, Travis C; Wisniewski, Stephen R; Jackson, Edwin K; Vagni, Vincent A; Bayır, Hülya; Clark, Robert S B; Dixon, C Edward; Janesko-Feldman, Keri L; Kochanek, Patrick M

2014-08-15

Secondary insults, such as hemorrhagic shock (HS), worsen outcome from traumatic brain injury (TBI). Both TBI and HS modulate levels of inflammatory mediators. We evaluated the addition of HS on the inflammatory response to TBI. Adult male C57BL6J mice were randomized into five groups (n=4 [naïve] or 8/group): naïve; sham; TBI (through mild-to-moderate controlled cortical impact [CCI] at 5 m/sec, 1-mm depth), HS; and CCI+HS. All non-naïve mice underwent identical monitoring and anesthesia. HS and CCI+HS underwent a 35-min period of pressure-controlled hemorrhage (target mean arterial pressure, 25-27 mm Hg) and a 90-min resuscitation with lactated Ringer's injection and autologous blood transfusion. Mice were sacrificed at 2 or 24 h after injury. Levels of 13 cytokines, six chemokines, and three growth factors were measured in serum and in five brain tissue regions. Serum levels of several proinflammatory mediators (eotaxin, interferon-inducible protein 10 [IP-10], keratinocyte chemoattractant [KC], monocyte chemoattractant protein 1 [MCP-1], macrophage inflammatory protein 1alpha [MIP-1α], interleukin [IL]-5, IL-6, tumor necrosis factor alpha, and granulocyte colony-stimulating factor [G-CSF]) were increased after CCI alone. Serum levels of fewer proinflammatory mediators (IL-5, IL-6, regulated upon activation, normal T-cell expressed, and secreted, and G-CSF) were increased after CCI+HS. Serum level of anti-inflammatory IL-10 was significantly increased after CCI+HS versus CCI alone. Brain tissue levels of eotaxin, IP-10, KC, MCP-1, MIP-1α, IL-6, and G-CSF were increased after both CCI and CCI+HS. There were no significant differences between levels after CCI alone and CCI+HS in any mediator. Addition of HS to experimental TBI led to a shift toward an anti-inflammatory serum profile--specifically, a marked increase in IL-10 levels. The brain cytokine and chemokine profile after TBI was minimally affected by the addition of HS.

The association between high-sensitivity C-reactive protein and metabolic risk factors in black and white South African women: a cross-sectional study.

PubMed

George, Cindy; Evans, Juliet; Micklesfield, Lisa K; Olsson, Tommy; Goedecke, Julia H

2018-01-01

High-sensitivity C-reactive protein (hsCRP) is associated with metabolic risk, however it is unclear whether the relationship is confounded by racial/ethnic differences in socioeconomic status (SES), lifestyle factors or central adiposity. The aims of the study was, (1) to investigate whether hsCRP levels differ by race/ethnicity; (2) to examine the race/ethnic-specific associations between hsCRP, HOMA-IR and serum lipids [total cholesterol (TC), triglycerides (TG), high-density lipoproteins (HDL-C) and low-density lipoproteins (LDL-C)]; and (3) to determine whether race/ethnic-specific associations are explained by SES, lifestyle factors or waist circumference (WC). The convenience sample comprised 195 black and 153 white apparently health women, aged 18-45 years. SES (education, assets and housing density) and lifestyle factors (alcohol use, physical activity and contraceptive use) were collected by questionnaire. Weight, height and WC were measured, and fasting blood samples collected for hsCRP, glucose, insulin, and lipids. Black women had higher age- and BMI-adjusted hsCRP levels than white women ( p  = 0.047). hsCRP was associated with HOMA-IR ( p  < 0.001), TG (p < 0.001), TC ( p  < 0.05), HDL-C (p < 0.05), and LDL-C ( p  < 0.05), independent of age and race/ethnicity. The association between hsCRP and lipids differed by race/ethnicity, such that hsCRP was positively associated with TG and LDL-C in white women, and inversely associated with HDL-C in black women. Higher hsCRP was also associated with higher TC in white women and lower TC in black women. Furthermore, when adjusting for SES and lifestyle factors, the associations between hsCRP, and TC and TG, remained, however the associations between hsCRP, and HDL-C and LDL-C, were no longer significant. Although circulating hsCRP may identify individuals at increased metabolic risk, the heterogeneity in these associations between racial/ethnic groups highlights the need for prospective studies investigating the role of hsCRP for risk prediction in different populations.

Maternal corticosterone reduces egg fertility and hatchability and increases the numbers of early dead embryos in eggs laid by quail hens selected for exaggerated adrenocortical stress responsiveness.

PubMed

Schmidt, J B; Satterlee, D G; Treese, S M

2009-07-01

Quail hens selected for exaggerated (HS, high stress) rather than reduced (LS, low stress) plasma corticosterone (B) response to brief restraint deposit more B into their egg yolks than do LS hens. Female progeny of HS hens implanted with B also show reduced egg production when compared with female offspring of LS- and HS-control and LS-B-implanted hens. Herein, LS and HS hens were implanted (s.c.) with empty (controls, CON) or B-filled silastic tubes to assess the interactive influences of maternal B-treatment with quail stress line on egg fertility (FERT), total egg hatchability (TOTHATCH) and fertile egg hatchability, and the percentages of embryonic mortality (early dead, ED; late dead) and pipped eggs. Mean FERT was dramatically reduced in eggs of HS compared with LS hens and B-implanted compared with CON-treated hens (P < 0.0001, both cases). Line x implant treatment FERT outcomes partitioned (P < 0.05) as follows: LS-B = LS-CON > HS-CON > HS-B. In addition, TOTHATCH was also affected by line (LS > HS; P < 0.0001) and implant treatment (CON > B-implant; P < 0.0002) and line x implant treatment TOTHATCH means differed (P < 0.05) as follows: LS-CON = LS-B = HS-CON > HS-B. Fertile egg hatchability was reduced (P < 0.05) in HS-B-treated hen eggs when compared with LS-B and HS-CON hen eggs and more (P < 0.05) ED embryos were found in eggs laid by HS-B-implanted hens than in any other treatment group. Late dead and pipped egg percentages were unaffected by any treatment. The findings are important to avian geneticists because they further emphasize the benefits that selection for reduced adrenocortical responsiveness has on hen reproductive performance. The maternal B findings also warn poultry and hatchery managers that unless hen stress during egg formation is avoided, negative consequences in FERT, TOTHATCH, and ED can result, particularly in hens genetically predisposed toward exaggerated adrenal stress responsiveness.

Predictive value of high-sensitivity troponin-I for future adverse cardiovascular outcome in stable patients with type 2 diabetes mellitus

PubMed Central

2014-01-01

Introduction High-sensitivity cardiac troponin I(hs-TnI) and T levels(hs-TnT) are sensitive biomarkers of cardiomyocyte turnover or necrosis. Prior studies of the predictive role of hs-TnT in type 2 diabetes mellitus(T2DM) patients have yielded conflicting results. This study aimed to determine whether hs-TnI, which is detectable in a higher proportion of normal subjects than hsTnT, is associated with a major adverse cardiovascular event(MACE) in T2DM patients. Methods and results We compared hs-TnI level in stored serum samples from 276 consecutive patients (mean age 65 ± 10 years; 57% male) with T2DM with that of 115 age-and sex-matched controls. All T2DM patients were prospectively followed up for at least 4 years for incidence of MACE including heart failure(HF), myocardial infarction(MI) and cardiovascular mortality. At baseline, 274(99%) patients with T2DM had detectable hs-TnI, and 57(21%) had elevated hs-TnI (male: 8.5 ng/L, female: 7.6 ng/L, above the 99th percentile in healthy controls). A total of 43 MACE occurred: HF(n = 18), MI(n = 11) and cardiovascular mortality(n = 14). Kaplan-Meier analysis showed that an elevated hs-TnI was associated with MACE, HF, MI and cardiovascular mortality. Although multivariate analysis revealed that an elevated hs-TnI independently predicted MACE, it had limited sensitivity(62.7%) and positive predictive value(38.5%). Contrary to this, a normal hs-TnI level had an excellent negative predictive value(92.2%) for future MACE in patients with T2DM. Conclusion The present study demonstrates that elevated hs-TnI in patients with T2DM is associated with increased MACE, HF, MI and cardiovascular mortality. Importantly, a normal hs-TnI level has an excellent negative predictive value for future adverse cardiovascular events during long-term follow-up. PMID:24661773

Characteristics and long-term outcome of 15 episodes of systemic lupus erythematosus-associated hemophagocytic syndrome.

PubMed

Lambotte, Olivier; Khellaf, Mehdi; Harmouche, Hicham; Bader-Meunier, Brigitte; Manceron, Véronique; Goujard, Cécile; Amoura, Zahir; Godeau, Bertrand; Piette, Jean-Charles; Delfraissy, Jean-François

2006-05-01

Reactive hemophagocytic syndrome (HS) occurs mainly in the setting of serious infections and lymphomas. HS can occur in the course of 2 active systemic diseases, without simultaneous infection: adult Still disease and systemic lupus erythematosus (SLE). Observations of specific lupus-associated HS are rare, and the long-term outcome of these patients with active SLE is unknown. We retrospectively studied 15 episodes of SLE-associated HS in 12 patients (10 women, 2 men) and noted the long-term outcome. HS occurred at a mean age of 25 years. All patients were febrile with >or=2 cytopenias, and bone marrow aspiration indicated hemophagocytosis. HS revealed SLE in 9 patients and recurred in 3. The main features of SLE-associated HS were a low frequency of hepatosplenomegaly, a high frequency of heart involvement (5 pericarditis, 4 myocarditis requiring transfer to intensive care unit), and a low C-reactive protein level (mean, 15 mg/L). Cutaneous-mucous symptoms of SLE, arthritis, and nephritis were present respectively in 8 (53%), 6 (40%), and 4 (27%) episodes, but symptoms of SLE were absent in 4 episodes at admission. All patients had anti-nuclear antibodies when the HS occurred. Anti-double-stranded DNA antibodies were present in 12 episodes. Treatment was steroids in 14 cases but cyclophosphamide was the only treatment able to control HS in 2 cases. All the cases of SLE-associated HS were controlled by the immunosuppressive regimen. Intravenous immunoglobulins seemed poorly effective. No infectious agent was found. Clinical presentations of the 23 patients with SLE-associated HS described in the literature were reviewed and were similar to those of the current series. The mean follow-up was 88 months (range, 7-240 mo). One patient died at 15 months (sepsis). Among the 5 patients with a follow-up >8 years, 4 always had active disease. During the follow-up of SLE, immunosuppressive drugs were added in 8 patients (cyclophosphamide in 7, azathioprine in 3, mycophenolate mofetil in 2) with significant adverse drug reactions. In the long-term, SLE-associated HS seems to define a severe SLE form with frequent flares, possible HS recurrences, and the need for prolonged immunosuppression.

The administration of hydrogen sulphide prior to ischemic reperfusion has neuroprotective effects in an acute stroke model

PubMed Central

Kim, Kyung-Won; Kim, Jeong-Kon; Jeon, Sang-Beom; Jung, Seung-Chae; Choi, Choong-Gon; Kim, Sang-Tae; Kim, Jinil; Ham, Su Jeong; Shim, Woo-Hyun; Sung, Yu Sub; Ha, Hyun Kwon; Choi, Yoonseok

2017-01-01

Emerging evidence has suggested that hydrogen sulfide (H2S) may alleviate the cellular damage associated with cerebral ischemia/reperfusion (I/R) injury. In this study, we assessed using 1H-magnetic resonance imaging/magnetic resonance spectroscopy (1H-MRI/MRS) and histologic analysis whether H2S administration prior to reperfusion has neuroprotective effects. We also evaluated for differences in the effects of H2S treatment at 2 time points. 1H-MRI/MRS data were obtained at baseline, and at 3, 9, and 24 h after ischemia from 4 groups: sham, control (I/R injury), sodium hydrosulfide (NaHS)-30 and NaHS-1 (NaHS delivery at 30 and 1 min before reperfusion, respectively). The total infarct volume and the midline shift at 24 h post-ischemia were lowest in the NaHS-1, followed by the NaHS-30 and control groups. Peri-infarct volume was significantly lower in the NaHS-1 compared to NaHS-30 and control animals. The relative apparent diffusion coefficient (ADC) in the peri-infarct region showed that the NaHS-1 group had significantly lower values compared to the NaHS-30 and control animals and that NaHS-1 rats showed significantly higher relative T2 values in the peri-infarct region compared to the controls. The relative ADC value, relative T2 value, levels of N-acetyl-L-aspartate (NAA), and the NAA, glutamate, and taurine combination score (NGT) in the ischemic core region at 24 h post-ischemia did not differ significantly between the 2 NaHS groups and the control except that the NAA and NGT values were higher in the peri-infarct region of the NaHS-1 animals at 9 h post-ischemia. In the ischemic core and peri-infarct regions, the apoptosis rate was lowest in the NaHS-1 group, followed by the NaHS-30 and control groups. Our results suggest that H2S treatment has neuroprotective effects on the peri-infarct region during the evolution of I/R injury. Furthermore, our findings indicate that the administration of H2S immediately prior to reperfusion produces the highest neuroprotective effects. PMID:29161281

Cardiovascular risk stratification in hemodialysis patients in the era of highly sensitive troponins: should we choose between hs-troponin I and hs-troponin T?

PubMed

Bargnoux, Anne-Sophie; Kuster, Nils; Patrier, Laure; Dupuy, Anne-Marie; Tachon, Gaelle; Maurice, Francois; Badaoui, Bouchra; Chalabi, Lotfi; Badiou, Stéphanie; Deleuze, Sebastien; Leray-Moragues, Hélène; Morena, Marion; Canaud, Bernard; Cristol, Jean-Paul

2016-04-01

New highly sensitive (hs) assays have challenged the interpretation of cardiac troponins (cTn). The present study was designed to evaluate simultaneously conventional cTnT and cTnI together with their corresponding highly sensitive determinations in stable hemodialysis (HD) patients. Ability of cTn to stratify HD patient risk was assessed. A total of 224 stable HD patients was included in this observational study. cTnT and hs-cTnT were measured using Roche cTnT/hs-cTnT assays based on a Cobas e601® analyzer. cTnI and hs-cTnI were measured using Beckman AccuTnI/hs-TnI IUO assays on Access II system. Patients were followed up prospectively during 9 years. Relationship between cTn level and mortality was assessed through Cox survival analysis. The median cTnT and cTnI concentrations were 38.5 ng/L (IQR, 18.8-76) and 10 ng/L (IQR, 10-20), respectively. The median hs-cTnT and hs-cTnI concentrations were 62.5 ng/L (IQR, 38.8-96.3) and 13.9 ng/L (IQR, 8.4-23.6), respectively. The prevalence of values above the 99th percentile was significantly more marked with cTnT (85.3 and 97.8% for conventional and hs cTnT, respectively) than with cTnI (7.6 and 67.4% for conventional and hs cTnI, respectively). During the follow-up, 167 patients died, mainly from cardiac cause (n=77). The optimized cut-off values, determined by bootstrap method, predicting mortality were 38, 69, 20 and 11 ng/L for cTnT, hs-cTnT, cTnI and hs-cTnI, respectively. After full adjustment, elevated plasma concentrations of all troponin were significant predictors of mortality. A large proportion of patients free of acute coronary syndrome (ACS) has hs-cTn I or T higher than the 99th percentile which could be seen as a limiting factor for ACS screening. However, all generation and type of troponin assays could be reliable indicators of prognosis risk in HD patients.

Dietary patterns, metabolic markers and subjective sleep measures in resident physicians.

PubMed

Mota, Maria Carliana; De-Souza, Daurea Abadia; Rossato, Luana Thomazetto; Silva, Catarina Mendes; Araújo, Maria Bernadete Jeha; Tufik, Sérgio; de Mello, Marco Túlio; Crispim, Cibele Aparecida

2013-10-01

Shiftwork is common in medical training and is necessary for 24-h hospital coverage. Shiftwork poses difficulties not only because of the loss of actual sleep hours but also because it can affect other factors related to lifestyle, such as food intake, physical activity level, and, therefore, metabolic patterns. However, few studies have investigated the nutritional and metabolic profiles of medical personnel receiving training who are participating in shiftwork. The aim of the present study was to identify the possible negative effects of food intake, anthropometric variables, and metabolic and sleep patterns of resident physicians and establish the differences between genders. The study included 72 resident physicians (52 women and 20 men) who underwent the following assessments: nutritional assessment (3-day dietary recall evaluated by the Adapted Healthy Eating Index), anthropometric variables (height, weight, body mass index, and waist circumference), fasting metabolism (lipids, cortisol, high-sensitivity C-reactive protein [hs-CRP], glucose, and insulin), physical activity level (Baecke questionnaire), sleep quality (Pittsburgh Sleep Quality Index; PSQI), and sleepiness (Epworth Sleepiness Scale; ESS). We observed a high frequency of residents who were overweight or obese (65% for men and 21% for women; p = 0.004). Men displayed significantly greater body mass index (BMI) values (p = 0.002) and self-reported weight gain after the beginning of residency (p = 0.008) than women. Poor diet was observed for both genders, including the low intake of vegetables and fruits and the high intake of sweets, saturated fat, cholesterol, and caffeine. The PSQI global scores indicated significant differences between genders (5.9 vs. 7.5 for women and men, respectively; p = 0.01). Women had significantly higher mean high-density lipoprotein cholesterol (HDL-C; p < 0.005), hs-CRP (p = 0.04), and cortisol (p = 0.009) values than men. The elevated prevalence of hypertriglyceridemia and abnormal values of low-density lipoprotein cholesterol (LDL-C; >100 mg/dL) were observed in most individuals. Higher than recommended hs-CRP levels were observed in 66% of the examined resident physicians. Based on current recommendations, a high prevalence of low sleep quality and excessive daytime sleepiness was identified. These observations indicate the need to monitor health status and develop actions to reassess the workload of medical residency and the need for permission to perform extra night shifts for medical residents to avoid worsening health problems in these individuals.

Mechanical Stress and Antioxidant Protection in the Retina of Hindlimb Suspended Rats

NASA Technical Reports Server (NTRS)

Glass, Aziza; Theriot, Corey A.; Alway, Stephen E.; Zanello, Susana B.

2012-01-01

It has been postulated that hindlimb suspension (HS) causes a cephalad fluid shift in quadrupeds similar to that occurring to humans in microgravity. Therefore, HS may provide a suitable animal model in which to recapitulate the ocular changes observed in the human Visual Impairment and Intracranial Pressure (VIIP) syndrome. This work reports preliminary results from a tissue sharing project using 34 week-old Brown Norway rats. Two different experiments compared normal posture controls and HS rats for 2 weeks and rats exposed to HS for 2 weeks but allowed to recover in normal posture for 2 additional weeks. The effects of two nutritional countermeasures, green tea extract (GT) and plant polyphenol resveratrol (Rv), were also evaluated. Green tea contains the antioxidant epigallocatechin gallate (EGCG). qPCR gene expression analysis of selected targets was performed on RNA from isolated retinas, and histologic analysis was done on one fixed eye per rat. The transcription factor early growth response protein 1 (Egr1) was upregulated almost 2-fold in HS retinas relative to controls (P = 0.059), and its expression returned to control levels after 2 weeks of recovery in normal posture (P = 0.023). HS-induced upregulation of Egr1 was attenuated (but not significantly) in retinas from rats fed an antioxidant rich (GT extract) diet. In rats fed the GT-enriched diet, antioxidant enzymes were induced, evidenced by the upregulation of the gene heme oxygenase 1 (Hmox1) (P = 0.042) and the gene superoxide dismutase 2 (Sod2) (P = 0.0001). Egr1 is a stretch-activated transcription factor, and the Egr1 mechanosensitive response to HS may have been caused by a change in the translaminal pressure and/or mechanical deformation of the eye globe. The observed histologic measurements of the various retinal layers in the HS rats were lower in value than those of the control animal (n = 1), however insufficient data were available for statistical analysis. Aquaporin 4, a water-selective channel involved in interstitial fluid homeostasis, showed an upregulated trend in HS retinas; however, these results are preliminary. Total retinal thickness increased significantly (P = 0.049) in HS rats fed a resveratrol enriched diet compared to HS rats on a normal diet. This change appeared to be reversed during the 2 weeks of recovery post HS, but no differences in retina thickness were observed between HS animals and HS recovered animals when both groups consumed a normal diet. The reversibility of the increase in retinal thickness induced by resveratrol during HS may therefore reflect an interaction between the stress provoked by HS and the cytoprotective mechanisms elicited by resveratrol

Reconstructing the climatic ultrastructure and aquatic biotic communities response to Heinrich stadials in the continental northern Neotropics

NASA Astrophysics Data System (ADS)

Cohuo, Sergio; Macario, Laura; Sylvestre, Florence; Pailles, Christine; Kutterolf, Steffen; Pérez, Liseth; Curtis, Jason; Schwalb, Antje

2016-04-01

Heinrich stadials (HS) are recognized as fast-acting "pulses" of global rapid environmental change that affect the climate and cause alterations in species composition and distribution. Past changes in aquatic ecosystems due to HSs may be an analog for future disruptions caused by climate change in the Neotropics. Our aim is to provide high resolution water temperature and conductivity records for HSs (HS1-HS6) in the northern Neotropics and identify their effects on aquatic communities. We analyzed the geochemical sediment composition (TIC and TOC) and quantified ostracode and diatom fossil abundances in cores PI-6 (73m long, from71m water depth) and PI-2 (84m long and from 54m water depth) from Lake Petén Itzá, Guatemala. Sediment cores were dated using a combination of radiocarbon and tephra chronology. Taxonomical analysis revealed that the ostracode fauna through all HSs had an exclusive tropical composition, reflecting that water temperatures remained warm, likely within the current tolerant range (26-33°C) observed for modern species inhabiting Central American lakes. Because of these warm conditions on the lake ecosystem, we infer that there was not a large change in temperatures as suggested by Hodell et al. (2012), but a small on such at the 5°C suggested by Correa-Metrio et al. (2012). Sediments during HSs are dominated by gypsum, suggesting variable water solute composition. Low TIC and TOC values during HSs indicate that these variations resulted from a decrease in precipitation and prevailing dry conditions. Bioproxy composition however, suggests sharp climatic transitions from humid to arid (HS5, HS3and H1) and from arid to humid (HS4, HS2). HS6 (63.2-60.1 ka BP) was characterized by domination of benthic diatoms and nektobenthic Cypria petenensis, Paracythereis opesta and Pseudocandona sp. ostracode species, suggesting low lake levels with predominance of littoral conditions. HS5 (50-47ka BP), HS3 (32.7-31.3ka BP) and HS1 (18-15.6ka BP) were characterized by rapid changes from planktonic to benthic diatoms, suggesting deepening of water. These transitions occurred at the onset of HS5, the middle-end of HS3 and the end of HS1. Lake ecosystem, thus had different response to these events. Ostracode community during HS5 was characterized by the nektobenthic and conductivity tolerant ostracodes Cypridopsis vidua, C. petenensis, P. opesta and Heterocypris putei suggesting low lake levels prevailing with high conductivity. During HS1 and HS3 ostracode assemblages was mostly dominated by nektobenthic species with the emergence of conductivity-tolerant H. putei at the end of the periods. Thus, humid conditions dominated during these HSs, but they ended with a rapid transition to a dry environment with increasing of conductivity. HS4 (38.3-40.2ka BP) and HS2 (24.3-26.5ka BP) showed abrupt changes from benthic to planktonic diatoms suggesting increasing water depth due to increased precipitation rates. The HS4 ostracode assemblage was initially dominated by benthic species such as Pseudocandona sp and Darwinula stevensoni but later on only necktobenthic species were present. Similar patter occurred during HS2, but the dominance of littoral-related species lasted longer, suggesting predominant dry conditions and low lake levels. The occurrence of necktobenthic species at the end of the period suggests increase of humidity. Our study highlights good agreement of the cores analyzed from different water depths and the applicability of multiproxy approach for a high resolution interpretation of past climate forces in northern Neotropics.

Estimation and Mitigation of Unmodeled Errors for a Pseudolite Based Reference System

DTIC Science & Technology

2005-03-01

42700− hs)× 10−6 5Ts∆hu [( 1− ∆hAPL 42700− hs )5 − ( 1− ∆hAPL + ∆hu 42700− hs )5] Ru + Ns × (13000− hs)× 10−6 5∆hu [( 1− ∆hAPL 13000− hs )5 − ( 1− ∆hAPL...hu 13000− hs )5] Ru (1.1) where Ns = 2.277(10 −6) RH T 2s ( 10 7.4475(Ts−273K) Ts−38.3K ) (1.2) and τAPL,u = tropospheric delay for mobile receiver...humidity (percent) Ns = surface refractivity 1-8 Bouska and Raquet [4] discuss the effects of tropospheric reduction efforts re- lating to DGPS and

Studies on evaluating and removing subsurface damage on the ground surface of CLEARCERAM-Z HS

NASA Astrophysics Data System (ADS)

Akitaya, Hiroshi; Yamashita, Takuya; Ohshima, Norio; Iye, Masanori; Maihara, Toshinori; Tokoro, Hitoshi; Takahashi, Keisuke

2010-07-01

We evaluated depth of subsurface damage on a ground surface of the ultra low expansion glass-ceramics CLEARCERAMR®-Z HS (CC-Z HS) by Ohara Inc., which is one of the candidates for material for segmented mirrors of the Thirty Meter Telescope. We made polishing spots of Magnetorheological Finishing on the ground surface of CC-Z HS and measured exposed subsurface damage features on the spot surface. We also studied on hydrofluoric acid etching of the CC-Z HS ground surface, which is expected to be an effective method to remove a subsurface damage layer compared with time-consuming polishing. We etched small ground surfaces of CC-Z HS and evaluated its uniformity.

Improving the Diagnostic Specificity of CT for Early Detection of Lung Cancer: 4D CT-Based Pulmonary Nodule Elastometry

DTIC Science & Technology

2013-08-01

transformation models, such as thin - plate spline (1-3) or elastic-body spline (4, 5), is locally controlled. One of the main motivations behind the...research project. References: 1. Bookstein FL. Principal warps: thin - plate splines and the decomposition of deformations. IEEE Transactions on Pattern...Rohr K, Stiehl HS, Sprengel R, Buzug TM, Weese J, Kuhn MH. Landmark-based elastic registration using approximating thin - plate splines . IEEE Transactions

Hippocampal sclerosis of aging, a prevalent and high-morbidity brain disease

PubMed Central

Smith, Charles D.; Abner, Erin L.; Wilfred, Bernard J.; Wang, Wang-Xia; Neltner, Janna H.; Baker, Michael; Fardo, David W.; Kryscio, Richard J.; Scheff, Stephen W.; Jicha, Gregory A.; Jellinger, Kurt A.; Van Eldik, Linda J.; Schmitt, Frederick A.

2013-01-01

Hippocampal sclerosis of aging (HS-Aging) is a causative factor in a large proportion of elderly dementia cases. The current definition of HS-Aging rests on pathologic criteria: neuronal loss and gliosis in the hippocampal formation that is out of proportion to AD-type pathology. HS-Aging is also strongly associated with TDP-43 pathology. HS-Aging pathology appears to be most prevalent in the oldest-old: autopsy series indicate that 5–30 % of nonagenarians have HS-Aging pathology. Among prior studies, differences in study design have contributed to the study-to-study variability in reported disease prevalence. The presence of HS-Aging pathology correlates with significant cognitive impairment which is often misdiagnosed as AD clinically. The antemortem diagnosis is further confounded by other diseases linked to hippocampal atrophy including frontotemporal lobar degeneration and cerebrovascular pathologies. Recent advances characterizing the neurocognitive profile of HS-Aging patients have begun to provide clues that may help identify living individuals with HS-Aging pathology. Structural brain imaging studies of research subjects followed to autopsy reveal hippocampal atrophy that is substantially greater in people with eventual HS-Aging pathology, compared to those with AD pathology alone. Data are presented from individuals who were followed with neurocognitive and neuroradiologic measurements, followed by neuropathologic evaluation at the University of Kentucky. Finally, we discuss factors that are hypothesized to cause or modify the disease. We conclude that the published literature on HS-Aging provides strong evidence of an important and under-appreciated brain disease of aging. Unfortunately, there is no therapy or preventive strategy currently available. PMID:23864344

A Sphingosine-1 Phosphate agonist (FTY720) limits trauma/hemorrhagic shock induced multiple organ dysfunction syndrome

PubMed Central

Bonitz, Joyce A.; Son, Julie Y.; Chandler, Benjamin; Tomaio, Jacquelyn N.; Qin, Yong; Prescott, Lauriston M.; Feketeova, Eleonora; Deitch, Edwin A.

2014-01-01

BACKGROUND Trauma/hemorrhagic shock is one of the major consequences of battlefield injury as well as civilian trauma. FTY720 (sphingosine-1 phosphate agonist) has the capability to decrease the activity of the innate and adaptive immune systems and, at the same time, maintain endothelial cell barrier function and vascular homeostasis during stress. For this reason, we hypothesize that FTY720, as part of resuscitation therapy, would limit T/HS induced multiple organ dysfunction syndrome (MODS) in a rodent trauma-hemorrhagic shock (T/HS) model. METHODS Rats subjected to trauma/sham-shock (T/SS) or T/HS (30 mm Hg × 90 min), were administered FTY720 (1 mg/kg) post-T/HS during volume resuscitation. Lung injury (permeability to Evans Blue dye), PMN priming (respiratory burst activity), and RBC rigidity were measured. In addition, lymph duct cannulated rats were used to quantify the effect of FTY720 on gut injury (permeability and morphology) and the biologic activity of T/HS vs. T/SS lymph on PMN-RB and RBC deformability. RESULTS T/HS-induced increased lung permeability, PMN priming and RBC rigidity were all abrogated by FTY720. The systemic protective effect of FTY720 was only partially at the gut level, since FTY720 did not prevent T/HS-induced gut injury (morphology or permeability,) however, it did abrogate T/HS lymph-induced increased respiratory burst and RBC rigidity. CONCLUSION FTY720 limited T/HS-induced MODS (lung injury, red cell injury, and neutrophil priming) as well as T/HS lymph bioactivity, although it did not limit gut injury. PMID:25004059

Effects of humic substances on the bioconcentration of polycyclic aromatic hydrocarbons: Correlations with spectroscopic and chemical properties of humic substances

DOE Office of Scientific and Technical Information (OSTI.GOV)

Haitzer, M.; Abbt-Braun, G.; Traunspurger, W.

1999-12-01

The presence of dissolved humic substances (HS, fulvic and humic acids) generally reduces the uptake of hydrophobic organic compounds into aquatic organisms. The extent of this effect depends both on the concentration and on the origin of the HS. The aim of this study was to investigate the role of qualitative differences between HS from different origins. The effects of seven different HS on the bioconcentration of pyrene and benzo[a]pyrene (BaP) in the nematode Caenorhabditis elegans were related to the spectroscopic and chemical properties of the HS. The effect of each humic material on the bioconcentration of pyrene or BaPmore » was quantified as a biologically determined partition coefficient K{sub DOC}. The authors observed significant linear relationships between K{sub DOC} and the atomic H/C ratio, the specific absorptivity at 254 nm, the content of aromatic carbons as determined by {sup 13}C nuclear magnetic resonance spectroscopy, the copper-complexing capacity, the content of phenolic OH groups, and the molecular weight of the HS. There was no discernible relationship of K{sub DOC} with the atomic (N + O)/C ratio, an indicator of the polarity of HS. Taken together, their results show that the variability in the effects of HS from different origins could be related to variations in bulk properties of the HS. Parameters describing the aromaticity of the humic materials seemed to be most useful for estimating effects of HS on the bioconcentration of pyrene and BaP.« less

Pro-inflammatory and atherogenic circulating factors in non-alcoholic fatty liver disease associated to metabolic syndrome.

PubMed

Lucero, Diego; Zago, Valeria; López, Graciela I; Graffigna, Mabel; Fainboim, Hugo; Miksztowicz, Verónica; Meroño, Tomás; Belli, Susana; Levalle, Oscar; Wikinski, Regina; Brites, Fernando; Berg, Gabriela; Schreier, Laura

2011-01-14

It is not elucidated if liver fat deposits associated to metabolic syndrome (MS) aggravate the atherogenic state. We evaluated, in MS patients, if the presence of non-alcoholic hepatic steatosis (HS) determines differences in inflammatory markers and VLDL characteristics. Seventy-five patients with MS were divided into 2 groups depending on the presence or absence of HS, assessed by ultrasound. Lipid profile, free fatty acids (FFA), VLDL composition, adiponectin, tumor necrosis factor-alpha (TNF-α), high sensitivity C-reactive protein (hs-CRP), and soluble adhesion molecules (sVCAM-1 and sICAM-1) were measured. HS patients presented increased triglycerides levels, HOMA-IR and FFA. Patients with HS showed a reduction in adiponectin (p = 0.04) and increase in hs-CRP (p = 0.02), independently of insulin-resistance (IR). FFA correlated positively with TNF-α (p = 0.04) and inversely with adiponectin (p = 0.01). hs-CRP correlated with all inflammatory markers, independently of IR: TNF-α (r = 0.34, p = 0.02), sVCAM-1 (r = 0.29 p = 0.03), sICAM-1 (r = 0.56, p = 0.01), adiponectin (r = -0.34, p = 0.04). HS patients presented higher VLDL mass and number of particles. Adiponectin correlated with VLDL cholesterol content (r = -0.47, p = 0.04), independently of IR. VLDL, once secreted, would suffer from changes, becoming more atherogenic. Simple HS would play an important role increasing cardiovascular risk, independently of IR. hs-CRP may represent a useful biomarker of this condition. Copyright © 2010 Elsevier B.V. All rights reserved.

Suicide Risk Among Holocaust Survivors Following Psychiatric Hospitalizations: A Historic Cohort Study.

PubMed

Lurie, Ido; Gur, Adi; Haklai, Ziona; Goldberger, Nehama

2018-01-01

The association between Holocaust experience, suicide, and psychiatric hospitalization has not been unequivocally established. The aim of this study was to determine the risk of suicide among 3 Jewish groups with past or current psychiatric hospitalizations: Holocaust survivors (HS), survivors of pre-Holocaust persecution (early HS), and a comparison group of similar European background who did not experience Holocaust persecution. In a retrospective cohort study based on the Israel National Psychiatric Case Register (NPCR) and the database of causes of death, all suicides in the years 1981-2009 were found for HS (n = 16,406), early HS (n = 1,212) and a comparison group (n = 4,286). Age adjusted suicide rates were calculated for the 3 groups and a logistic regression model was built to assess the suicide risk, controlling for demographic and clinical variables. The number of completed suicides in the study period was: HS-233 (1.4%), early HS-34 (2.8%), and the comparison group-64 (1.5%). Age adjusted rates were 106.7 (95% CI 93.0-120.5) per 100,000 person-years for HS, 231.0 (95% CI 157.0-327.9) for early HS and 150.7 (95% CI 113.2-196.6) for comparisons. The regression models showed significantly higher risk for the early HS versus comparisons (multivariate model adjusted OR = 1.68, 95% CI 1.09-2.60), but not for the HS versus comparisons. These results may indicate higher resilience among the survivors of maximal adversity compared to others who experienced lesser persecution.

Estimation of high sensitivity C-reactive protein in patients with periodontal disease and without coronary artery disease.

PubMed

Anitha, V; Nair, Sushma; Shivakumar, V; Shanmugam, M; Priya, B Meena; Rajesh, P

2015-01-01

HsCRP (Highly sensitive C reactive protein) is a global indicator for future vascular events in adults detected in blood stream 48 hours before the cardiovascular event. Periodontal disease may increase blood levels of inflammatory markers like IL-6, CRP and HsCRP. Hence the aim of the present study is to evaluate the presence of elevated HsCRP levels in chronic periodontitis patients. 100 patients who reported for cardiac master health check up were enrolled in the study. The periodontal status was assessed using periodontal probing pocket depth and clinical attachment level. The decayed, missing and filled tooth was recorded using DMFT index. The venous samples of these patients were obtained for recording HsCRP levels. Pearson correlation was used to analyze the relationship between HsCRP level and probing pocket depth, clinical attachment loss and DMFT. The correlation value was 0.051, 0.025 and 0.101 respectively, the correlation is statistically significant for probing pocket depth and clinical attachment level (P>0.05). Chi-square test was performed to study the association between gender and HsCRP, Diabetes Mellitus and HsCRP and Hypertension and HsCRP; the results showed that there is no significant association between any of the above mentioned factors and HsCRP level in blood. We found an increased level of HsCRP in patients with chronic periodontitis which revealed the susceptibility of these patients to cardiac diseases like myocardial infarction and stroke. Hence present day focus in the line of management of cardiac patient has changed from the periodontal perspective.

Effects of heat stress on production, somatic cell score and conception rate in Holsteins.

PubMed

Hagiya, Koichi; Hayasaka, Kiyoshi; Yamazaki, Takeshi; Shirai, Tatsuo; Osawa, Takefumi; Terawaki, Yoshinori; Nagamine, Yoshitaka; Masuda, Yutaka; Suzuki, Mitsuyoshi

2017-01-01

We examined the effects of heat stress (HS) on production traits, somatic cell score (SCS) and conception rate at first insemination (CR) in Holsteins in Japan. We used a total of 228 242 records of milk, fat and protein yields, and SCS for the first three lactations, as well as of CR in heifers and in first- and second-lactation cows that had calved for the first time between 2000 and 2012. Records from 47 prefectural weather stations throughout Japan were used to calculate the temperature-humidity index (THI); areas were categorized into three regional groups: no HS (THI < 72), mild HS (72 ≤ THI < 79), and moderate HS (THI ≥ 79). Trait records from the three HS-region groups were treated as three different traits and trivariate animal models were used. The genetic correlations between milk yields from different HS groups were very high (0.91 to 0.99). Summer calving caused the greatest increase in SCS, and in the first and second lactations this increase became greater as THI increased. In cows, CR was affected by the interaction between HS group and insemination month: with summer and early autumn insemination, there was a reduction in CR, and it was much larger in the mild- and moderate-HS groups than in the no-HS group. © 2016 Japanese Society of Animal Science.

Hibiscus sabdariffa Linnaeus aqueous extracts attenuate the progression of renal injury in 5/6 nephrectomy rats.

PubMed

Seujange, Yuyen; Leelahavanichkul, Asada; Yisarakun, Waranurin; Khawsuk, Witoon; Meepool, Ardool; Phamonleatmongkol, Ponlapat; Saechau, Walai; Onlamul, Winita; Tantiwarattanatikul, Pansa; Oonsook, Worapong; Eiam-Ong, Somchai; Eiam-Ong, Somchit

2013-01-01

Hibiscus sabdariffa Linn. (HS) is a tropical wild plant with antioxidant, antibacterial, antihypertensive, and lipid-lowering properties. In several animal models, HS aqueous extracts reduced the severity of the multi-organ injuries such as hypertension and diabetic nephropathy. One of the multiorgan injuries is chronic kidney disease (CKD), which results from the loss of nephron function. HS was used in a 5/6 nephrectomy (5/6 Nx) rat model to determine if it could attenuate the progression of CKD. HS (250 mg/kg/day) or placebo was orally administered to 5/6 Nx male Sprague-Dawley rats. The Nx+HS group had fewer renal injuries as measured by blood urea nitrogen, serum creatinine, creatinine clearance, and renal pathology when compared with the Nx group. In order to determine which property of HS, either vasodilatory and/or antioxidant, was important in attenuating the progression of CKD, systolic blood pressure (SBP) and serum levels of malondialdehyde (MDA) were assessed. In the Nx+HS group, the SBP and the serum levels of MDA were significantly lower at Week 7. In conclusion, through either antihypertensive and/or antioxidant properties, HS was able to attenuate the progression of renal injury after 5/6 Nx. Hence, HS should be considered as one of the new, promising drugs that can be used to attenuate the progression of CKD.

Phospholipase D and phosphatidic acid mediate heat stress induced secondary metabolism in Ganoderma lucidum.

PubMed

Liu, Yong-Nan; Lu, Xiao-Xiao; Chen, Dai; Lu, Ya-Ping; Ren, Ang; Shi, Liang; Zhu, Jing; Jiang, Ai-Liang; Yu, Han-Shou; Zhao, Ming-Wen

2017-11-01

Phospholipid-mediated signal transduction plays a key role in responses to environmental changes, but little is known about the role of phospholipid signalling in microorganisms. Heat stress (HS) is one of the most important environmental factors. Our previous study found that HS could induce the biosynthesis of the secondary metabolites, ganoderic acids (GA). Here, we performed a comprehensive mass spectrometry-based analysis to investigate HS-induced lipid remodelling in Ganoderma lucidum. In particular, we observed a significant accumulation of phosphatidic acid (PA) on HS. Further genetic tests in which pld-silencing strains were constructed demonstrated that the accumulation of PA is dependent on HS-activated phospholipase D (PLD) hydrolysing phosphatidylethanolamine. Furthermore, we determined the role of PLD and PA in HS-induced secondary metabolism in G. lucidum. Exogenous 1-butanol, which decreased PLD-mediated formation of PA, reverses the increased GA biosynthesis that was elicited by HS. The pld-silenced strains partly blocked HS-induced GA biosynthesis, and this block can be reversed by adding PA. Taken together, our results suggest that PLD and PA are involved in the regulation of HS-induced secondary metabolism in G. lucidum. Our findings provide key insights into how microorganisms respond to heat stress and then consequently accumulate secondary metabolites by phospholipid remodelling. © 2017 Society for Applied Microbiology and John Wiley & Sons Ltd.

High mortality in cirrhotic patients following hemorrhagic stroke.

PubMed

Hung, Tsung-Hsing; Hsieh, Yu-Hsi; Tseng, Kuo-Chih; Tseng, Chih-Wei; Lee, Hsing-Feng; Tsai, Chih-Chun; Tsai, Chen-Chi

2015-06-01

The impact of hemorrhagic stroke (HS) on the mortality of cirrhotic patients is unknown. To evaluate the morality risk of HS in cirrhotic patients, we used the Taiwan National Health Insurance Database to evaluate cirrhotic patients with HS who were discharged between 1 January and 31 December 2007. In total, there were 321 cirrhotic patients with HS. We randomly selected 3210 cirrhotic patients without HS as a comparison group. The 30 and 90 day mortality rates were 29.6% and 43.0% in the HS group, and 9.1% and 17.7% in the comparison group, respectively (p<0.001). After Cox proportional hazard regression model adjustment of patients' sex, age, and other comorbid disorders, the hazard ratio (HR) for 90 day mortality in the HS group was 3.89 (95% confidence interval [CI] 3.20-4.71, p<0.001), compared to the comparison group. In the subgroup analysis, the HR for 90 day mortality in the subarachnoid hemorrhage and other HS groups were 7.93 (95% CI 5.23-12.0, p<0.001) and 3.51 (95% CI 2.85-4.32, p<0.001), respectively, compared to the comparison group. In conclusion, HS is associated with a very high 90 day mortality risk in cirrhotic patients, in whom subarachnoid hemorrhage can also increase the risk of mortality eight-fold. Copyright © 2015 Elsevier Ltd. All rights reserved.

Chromatin structure of the LCR in the human β-globin locus transcribing the adult δ- and β-globin genes.

PubMed

Kim, Seoyeon; Kim, Yea Woon; Shim, Sung Han; Kim, Chul Geun; Kim, Aeri

2012-03-01

The β-like globin genes are transcribed in a developmental stage specific fashion in erythroid cells. The specific transcription of globin genes is conferred by the locus control region (LCR), but the chromatin structure of the LCR in the human adult β-globin locus transcribing the δ- and β-globin genes is not clear. Here, we employed hybrid MEL cells that contain a human chromosome 11. The δ- and β-globin genes were highly transcribed in hybrid MEL/ch11 cells after transcriptional induction. LCR HS3 and HS2 were strongly occupied by erythroid specific transcriptional activators and co-factors in the induced locus. These HSs, but not HS4 and HS1, were in close proximity with the active globin genes as revealed by high resolution 3C experiments. The active features at HS3 were markedly established after transcriptional induction, while HS2 was in a relatively active conformation before the induction. Unexpectedly, HS1 did not show notable active features except histone hyperacetylation. Taken together, the LCR of the human β-globin locus transcribing the adult δ- and β-globin genes has HS specific chromatin structure. The structure at each HS, which is different from the locus transcribing the fetal globin genes, might relate to its role in transcribing the adult genes. Copyright © 2011 Elsevier Ltd. All rights reserved.

The validity and reliability of a dynamic neuromuscular stabilization-heel sliding test for core stability.

PubMed

Cha, Young Joo; Lee, Jae Jin; Kim, Do Hyun; You, Joshua Sung H

2017-10-23

Core stabilization plays an important role in the regulation of postural stability. To overcome shortcomings associated with pain and severe core instability during conventional core stabilization tests, we recently developed the dynamic neuromuscular stabilization-based heel sliding (DNS-HS) test. The purpose of this study was to establish the criterion validity and test-retest reliability of the novel DNS-HS test. Twenty young adults with core instability completed both the bilateral straight leg lowering test (BSLLT) and DNS-HS test for the criterion validity study and repeated the DNS-HS test for the test-retest reliability study. Criterion validity was determined by comparing hip joint angle data that were obtained from BSLLT and DNS-HS measures. The test-retest reliability was determined by comparing hip joint angle data. Criterion validity was (ICC2,3) = 0.700 (p< 0.05), suggesting a good relationship between the two core stability measures. Test-retest reliability was (ICC3,3) = 0.953 (p< 0.05), indicating excellent consistency between the repeated DNS-HS measurements. Criterion validity data demonstrated a good relationship between the gold standard BSLLT and DNS-HS core stability measures. Test-retest reliability data suggests that DNS-HS core stability was a reliable test for core stability. Clinically, the DNS-HS test is useful to objectively quantify core instability and allow early detection and evaluation.

Simultaneous determination of traces of pyrethroids, organochlorines and other main plant protection agents in agricultural soils by headspace solid-phase microextraction-gas chromatography.

PubMed

Fernandez-Alvarez, Maria; Llompart, Maria; Lamas, J Pablo; Lores, Marta; Garcia-Jares, Carmen; Cela, Rafael; Dagnac, Thierry

2008-04-25

A solvent-free and simple method based on headspace solid-phase microextraction (HS-SPME) was developed in order to determine simultaneously 36 common pesticides and breakdown products (mostly pyrethroids and organochlorine compounds) in soil. The analysis was carried out by gas chromatography with micro-electron-capture detection (GC-microECD). As far as we know, this is the first study about the SPME of pyrethroid insecticides from soil. Factors such as extraction temperature, matrix modification by addition of water, salt addition (% NaCl) and fiber coating were considered in the optimization of the HS-SPME. To this end, a 3 x 2(3-1) fractional factorial design was performed. The results showed that temperature and fiber coating were the most significant variables affecting extraction efficiency. A suitable sensitivity for all investigated compounds was achieved at 100 degrees C by extracting soil samples wetted with 0.5 mL of ultrapure water (0% NaCl) employing a polyacrylate (PA) coating fiber. Using the recommended extraction conditions with GC-microECD, a linear calibration could be achieved over a range of two orders of magnitude for both groups of analytes. Limits of detection (LODS) at the sub-ng g(-1) level were attained and relative standard deviations (RSDs) were found to be lower than 14% for both groups of pesticides. Matrix effects were investigated by the analysis of different soil samples fortified with the target compounds. The method accuracy was assessed and good recovery values (>70%, in most cases) were obtained. The method was also validated with a certified reference material (RTC-CRM818-050), which was quantified using a standard addition protocol. Finally, the proposed HS-SPME-GC-microECD methodology was further applied to the screening of environmental soil samples for the presence of the target pesticides.

Detection of Sleeping Beauty transposition in the genome of host cells by non-radioactive Southern blot analysis

DOE Office of Scientific and Technical Information (OSTI.GOV)

Aravalli, Rajagopal N., E-mail: aravalli@umn.edu; Park, Chang W.; Steer, Clifford J., E-mail: steer001@umn.edu

The Sleeping Beauty transposon (SB-Tn) system is being used widely as a DNA vector for the delivery of therapeutic transgenes, as well as a tool for the insertional mutagenesis in animal models. In order to accurately assess the insertional potential and properties related to the integration of SB it is essential to determine the copy number of SB-Tn in the host genome. Recently developed SB100X transposase has demonstrated an integration rate that was much higher than the original SB10 and that of other versions of hyperactive SB transposases, such as HSB3 or HSB17. In this study, we have constructed amore » series of SB vectors carrying either a DsRed or a human β-globin transgene that was encompassed by cHS4 insulator elements, and containing the SB100X transposase gene outside the SB-Tn unit within the same vector in cis configuration. These SB-Tn constructs were introduced into the K-562 erythroid cell line, and their presence in the genomes of host cells was analyzed by Southern blot analysis using non-radioactive probes. Many copies of SB-Tn insertions were detected in host cells regardless of transgene sequences or the presence of cHS4 insulator elements. Interestingly, the size difference of 2.4 kb between insulated SB and non-insulated controls did not reflect the proportional difference in copy numbers of inserted SB-Tns. We then attempted methylation-sensitive Southern blots to assess the potential influence of cHS4 insulator elements on the epigenetic modification of SB-Tn. Our results indicated that SB100X was able to integrate at multiple sites with the number of SB-Tn copies larger than 6 kb in size. In addition, the non-radioactive Southern blot protocols developed here will be useful to detect integrated SB-Tn copies in any mammalian cell type.« less

Association between serum vitamin D concentrations and inflammatory markers in the general adult population.

PubMed

Mellenthin, Liesa; Wallaschofski, Henri; Grotevendt, Anne; Völzke, Henry; Nauck, Matthias; Hannemann, Anke

2014-08-01

In recent years links among vitamin D deficiency, inflammation and cardio-metabolic disease were proposed. As information regarding the associations between vitamin D and inflammatory markers in the general population is sparse, we investigated the associations of 25-hydroxy vitamin D [25(OH)D] with high-sensitivity C-reactive protein (hs-CRP), fibrinogen and white blood cell count (WBC). The study population comprised 2723 men and women aged 25-88 years from the first follow-up of the Study of Health in Pomerania. Analyses of variance, linear and logistic regressions were performed to assess the associations between 25(OH)D and the three inflammatory markers. The models were adjusted for age, sex, waist circumference, diabetes mellitus, dyslipidemia, anti-inflammatory medication and month of blood sampling. The association between 25(OH)D and WBC was assessed separately in smokers (n = 718) and non-smokers (n = 2005) as effect modification was observed. We detected a U-shaped association between 25(OH)D and hs-CRP with a nadir of 21-25 ng/ml in fully-adjusted linear regression models with restricted cubic splines (p < 0.01; p' < 0.01). We further detected an inverse association between 25(OH)D and fibrinogen (p < 0.01). In addition, there was an inverse association between 25(OH)D and WBC in smokers (p = 0.02) but no association in non-smokers (p = 0.73). Our study confirms a potential role of 25(OH)D in chronic inflammation. Yet, different inflammatory biomarkers are differently associated with 25(OH)D. Beneficial effects of increasing 25(OH)D were observed for fibrinogen and WBC (in smokers only). In contrast, the U-shaped association between 25(OH)D and hs-CRP indicates that ever-increasing 25(OH)D concentrations may also be related to proinflammatory states. Copyright © 2014 Elsevier Inc. All rights reserved.

N-acetylcysteine reduces the renal oxidative stress and apoptosis induced by hemorrhagic shock.

PubMed

Moreira, Miriam Aparecida; Irigoyen, Maria Claudia; Saad, Karen Ruggeri; Saad, Paulo Fernandes; Koike, Marcia Kiyomi; Montero, Edna Frasson de Souza; Martins, José Luiz

2016-06-01

Renal ischemia/reperfusion injury induced by hemorrhagic shock (HS) and subsequent fluid resuscitation is a common cause of acute renal failure. The objective of this study was to evaluate the effect of combining N-acetylcysteine (NAC) with fluid resuscitation on renal injury in rats that underwent HS. Two groups of male Wistar rats were induced to controlled HS at 35 mm Hg mean arterial pressure for 60 min. After this period, the HS and fluid resuscitation (HS/R) group was resuscitated with lactate containing 50% of the blood that was withdrawn. The HS/R + NAC group was resuscitated with Ringer's lactate combined with 150 mg/kg of NAC and blood. The sham group animals were catheterized but were not subjected to shock. All animals were kept under anesthesia and euthanized after 120 min of fluid resuscitation or observation. Animals treated with NAC presented attenuation of histologic lesions, reduced oxidative stress, and apoptosis markers when compared with animals from the HS/R group. The serum creatinine was similar in all the groups. NAC is a promising drug for combining with fluid resuscitation to attenuate the kidney injury associated with HS. Copyright © 2016 Elsevier Inc. All rights reserved.

Enhanced interfacial interaction and antioxidative behavior of novel halloysite nanotubes/silica hybrid supported antioxidant in styrene-butadiene rubber

NASA Astrophysics Data System (ADS)

Lin, Jing; Luo, Yuanfang; Zhong, Bangchao; Hu, Dechao; Jia, Zhixin; Jia, Demin

2018-05-01

A novel antioxidant (HS-s-RT) to improve the mechanical properties and anti-aging performance of styrene-butadiene (SBR) composites was prepared by antioxidant intermediate p-aminodiphenylamine (RT) grafting on the surface of halloysite nanotubes/silica hybrid (HS) via the linkage of silane coupling agent. The analysis of SEM and rubber processing analyzer (RPA) demonstrated HS-s-RT was uniformly dispersed in SBR, and stronger interfacial interaction between HS-s-RT and SBR was formed. Consequently, SBR/HS-s-RT composites have improving mechanical properties. Furthermore, the test of the retention of mechanical properties, Fourier transform infrared spectroscopy with attenuated total reflectance (FTIR-ATR), and oxidation induction time (OIT) showed HS-s-RT can effectively improve the anti-aging effect of SBR composites than corresponding low molecular-weight antioxidant N-isopropyl-N‧-phenyl-4-phenylenediamin (4010NA). Then, the mechanism of thermo-oxidative aging of SBR/HS composites was also investigated, and the superior antioxidative efficiency is attributed to the uniform dispersion and excellent migration resistance of HS-s-RT. Hence, this novel antioxidant might open up new opportunities for the fabrication of high-performance rubber composites due to its superior anti-aging effect and reinforcement.

Site-specific identification of heparan and chondroitin sulfate glycosaminoglycans in hybrid proteoglycans.

PubMed

Noborn, Fredrik; Gomez Toledo, Alejandro; Green, Anders; Nasir, Waqas; Sihlbom, Carina; Nilsson, Jonas; Larson, Göran

2016-10-03

Heparan sulfate (HS) and chondroitin sulfate (CS) are complex polysaccharides that regulate important biological pathways in virtually all metazoan organisms. The polysaccharides often display opposite effects on cell functions with HS and CS structural motifs presenting unique binding sites for specific ligands. Still, the mechanisms by which glycan biosynthesis generates complex HS and CS polysaccharides required for the regulation of mammalian physiology remain elusive. Here we present a glycoproteomic approach that identifies and differentiates between HS and CS attachment sites and provides identity to the core proteins. Glycopeptides were prepared from perlecan, a complex proteoglycan known to be substituted with both HS and CS chains, further digested with heparinase or chondroitinase ABC to reduce the HS and CS chain lengths respectively, and thereafter analyzed by nLC-MS/MS. This protocol enabled the identification of three consensus HS sites and one hybrid site, carrying either a HS or a CS chain. Inspection of the amino acid sequence at the hybrid attachment locus indicates that certain peptide motifs may encode for the chain type selection process. This analytical approach will become useful when addressing fundamental questions in basic biology specifically in elucidating the functional roles of site-specific glycosylations of proteoglycans.

Defining Hand Stereotypies in Rett Syndrome: A Movement Disorders Perspective.

PubMed

Dy, Marisela E; Waugh, Jeff L; Sharma, Nutan; O'Leary, Heather; Kapur, Kush; D'Gama, Alissa M; Sahin, Mustafa; Urion, David K; Kaufmann, Walter E

2017-10-01

Hand stereotypies (HS) are a primary diagnostic criterion for Rett syndrome (RTT) but are difficult to characterize and quantify systematically. We collected video on 27 girls (2-12 years of age) with classic RTT who participated in a mecasermin trial. The present study focused exclusively on video analyses, by reviewing two five-minute windows per subject to identify the two most common HS. Three raters with expertise in movement disorders independently rated the five-minute windows using standardized terminology to determine the level of agreement. We iteratively refined the protocol in three stages to improve descriptive accuracy, categorizing HS as "central" or "peripheral," "simple" or "complex," scoring each hand separately. Inter-rater agreement was analyzed using Kappa statistics. In the initial protocol evaluating HS by video, inter-rater agreement was 20.7%. In the final protocol, inter-rater agreement for the two most frequent HS was higher than the initial protocol at 50%. Phenotypic variability makes standardized evaluation of HS in RTT a challenge; we achieved only 50% level of agreement and only for the most frequent HS. Therefore, objective measures are needed to evaluate HS. Copyright © 2017 Elsevier Inc. All rights reserved.

Hemophagocytic syndrome as the initial manifestation of systemic lupus erythematosus.

PubMed

Egües Dubuc, César Antonio; Uriarte Ecenarro, Miren; Meneses Villalba, Carlos; Aldasoro Cáceres, Vicente; Hernando Rubio, Iñaki; Belzunegui Otano, Joaquín

2014-01-01

Hemophagocytic syndrome (HS) occurs in autoimmune diseases and belongs to the hemophagocytic lymphohistiocytosis group of diseases. This paper describes the features of 2 patients with systemic lupus erythematosus (SLE) who presented HS as the initial clinical manifestation. Both patients had prolonged fever not associated to an infectious process and did not respond to broad-spectrum antibiotics. The diagnosis of HS secondary to SLE is complicated, because it has some features in common, but HS is characterized by hyperferritinemia, hipofibrinogemia, hypertriglyceridemia and a decrease in the erythrocyte sedimentation rate, unlike SLE. HS treatment when associated to SLE is not well established, but steroids and/or immunoglobulins are effective as the initial treatment, and in refractory cases, cyclosporine or cyclophosphamide may be associated. HS can be the initial manifestation of SLE and should be suspected in patients with organ enlargement, cytopenias, clotting disorders, liver disorders and prolonged fever unresponsive to antibiotics. Anakinra may be a treatment option in adult HS associated to SLE. Copyright © 2013 Elsevier España, S.L. All rights reserved.

Integrating Building Information Modeling and Health and Safety for Onsite Construction

PubMed Central

Ganah, Abdulkadir; John, Godfaurd A.

2014-01-01

Background Health and safety (H&S) on a construction site can either make or break a contractor, if not properly managed. The usage of Building Information Modeling (BIM) for H&S on construction execution has the potential to augment practitioner understanding of their sites, and by so doing reduce the probability of accidents. This research explores BIM usage within the construction industry in relation to H&S communication. Methods In addition to an extensive literature review, a questionnaire survey was conducted to gather information on the embedment of H&S planning with the BIM environment for site practitioners. Results The analysis of responses indicated that BIM will enhance the current approach of H&S planning for construction site personnel. Conclusion From the survey, toolbox talk will have to be integrated with the BIM environment, because it is the predominantly used procedure for enhancing H&S issues within construction sites. The advantage is that personnel can visually understand H&S issues as work progresses during the toolbox talk onsite. PMID:25830069

Exercise effects on the size and metabolic properties of soleus fibers in hindlimb-suspended rats

NASA Technical Reports Server (NTRS)

Graham, Scot C.; Roy, Roland R.; West, Steve P.; Thomason, Don; Baldwin, Kenneth M.

1989-01-01

The effects of four-week-long hind-limb suspension (HS) of rats on the size the soleus muscle fibers and the activity of succinate dehydrogenase (SDH) in dark and light ATPase fibers were investigated together with the efficacy of an endurance exercise (EX) program (daily treadmill exercise for 1.5 h/day at 20 m/min and a 30-percent grade) in ameliorating HS-induced changes. It was found that, in comparison to age-matched controls, the soleus wet weight decreased by 69 and 30 percent in HS and HS-EX rats, respectively, and the percent of dark ATPase fibers increased from 10 percent in controls to 19 and 17 percent, respectively. The values of the integrated fiber activity (activity/min times muscle area) showed a net loss of SDH in both the light and dark ATPase fibers of HS rats, but only in the light ATPase fibers of the HS-EX rats, indicating that exercise ameliorated but did not prevent the muscle fiber atrophy induced by HS.

Functional annotation of the genome unravels probiotic potential of Bacillus coagulans HS243.

PubMed

Kapse, N G; Engineer, A S; Gowdaman, V; Wagh, S; Dhakephalkar, P K

2018-05-30

Spore forming Bacillus species are widely used as probiotics for human dietary supplements and in animal feeds. However, information on genetic basis of their probiotic action is obscure. Therefore, the present investigation was undertaken to elucidate probiotic traits of B. coagulans HS243 through its genome analysis. Genome mining revealed the presence of an arsenal of marker genes attributed to genuine probiotic traits. In silico analysis of HS243 genome revealed the presence of multi subunit ATPases, ADI pathway genes, chologlycine hydrolase, adhesion proteins for surviving and colonizing harsh gastric transit. HS243 genome harbored vitamin and essential amino acid biosynthetic genes, suggesting the use of HS243 as a nutrient supplement. Bacteriocin producing genes highlighted the disease preventing potential of HS243. Thus, this work established that HS243 possessed the genetic repertoire required for surviving harsh gastric transit and conferring health benefits to the host which were further validated by wet lab evidences. Copyright © 2018. Published by Elsevier Inc.

Integrating building information modeling and health and safety for onsite construction.

PubMed

Ganah, Abdulkadir; John, Godfaurd A

2015-03-01

Health and safety (H&S) on a construction site can either make or break a contractor, if not properly managed. The usage of Building Information Modeling (BIM) for H&S on construction execution has the potential to augment practitioner understanding of their sites, and by so doing reduce the probability of accidents. This research explores BIM usage within the construction industry in relation to H&S communication. In addition to an extensive literature review, a questionnaire survey was conducted to gather information on the embedment of H&S planning with the BIM environment for site practitioners. The analysis of responses indicated that BIM will enhance the current approach of H&S planning for construction site personnel. From the survey, toolbox talk will have to be integrated with the BIM environment, because it is the predominantly used procedure for enhancing H&S issues within construction sites. The advantage is that personnel can visually understand H&S issues as work progresses during the toolbox talk onsite.

Spatial analysis of ecosystem service relationships to improve targeting of payments for hydrological services

PubMed Central

Manson, Robert H.; Ricketts, Taylor H.; Geissert, Daniel

2018-01-01

Payment for hydrological services (PHS) are popular tools for conserving ecosystems and their water-related services. However, improving the spatial targeting and impacts of PHS, as well as their ability to foster synergies with other ecosystem services (ES), remain challenging. We aimed at using spatial analyses to evaluate the targeting performance of México’s National PHS program in central Veracruz. We quantified the effectiveness of areas targeted for PHS in actually covering areas of high HS provision and social priority during 2003–2013. First, we quantified provisioning and spatial distributions of two target (water yield and soil retention), and one non-target ES (carbon storage) using InVEST. Subsequently, pairwise relationships among ES were quantified by using spatial correlation and overlap analyses. Finally, we evaluated targeting by: (i) prioritizing areas of individual and overlapping ES; (ii) quantifying spatial co-occurrences of these priority areas with those targeted by PHS; (iii) evaluating the extent to which PHS directly contribute to HS delivery; and (iv), testing if PHS targeted areas disproportionately covered areas with high ecological and social priority. We found that modelled priority areas exhibited non-random distributions and distinct spatial patterns. Our results show significant pairwise correlations between all ES suggesting synergistic relationships. However, our analysis showed a significantly lower overlap than expected and thus significant mismatches between PHS targeted areas and all types of priority areas. These findings suggest that the targeting of areas with high HS provisioning and social priority by Mexico’s PHS program could be improved significantly. This study underscores: (1) the importance of using maps of HS provisioning as main targeting criteria in PHS design to channel payments towards areas that require future conservation, and (2) the need for future research that helps balance ecological and socioeconomic targeting criteria. PMID:29462205

The Neurobiology of Self-Face Recognition in Depressed Adolescents with Low or High Suicidality

PubMed Central

Quevedo, Karina; Ng, Rowena; Scott, Hannah; Martin, Jodi; Smyda, Garry; Keener, Matt; Oppenheimer, Caroline W.

2017-01-01

This study sought to test whether the neurobiology of self-processing differentiated depressed adolescents with high suicidality from those with low suicidality and healthy controls (N=119, MAGE= 14.79, SD=1.64, Min=11.3, Max = 17.8). Participants completed a visual self-recognition task in the scanner during which they identified their own or an unfamiliar adolescent face across three emotional expressions (happy, neutral or sad). A 3 Group (HS, LS, HC) by two within subject factors [2 Self conditions (self, other) and 3 Emotions (happy, neutral, sad)] GLM yielded: 1) a main effect of Self condition with all participants showing higher activity in the right occipital, precuneus and fusiform during the self-versus other-face conditions; 2) a main effect of Group where all depressed youth showed higher dorsolateral prefrontal cortex activity than HC across all conditions, and with HS showing higher cuneus and occipital activity versus both LS and HC; and 3) a Group by Self by Emotion interaction with HS showing lower activity in both mid parietal, limbic and prefrontal areas in the Happy self versus other-face condition relative to the LS group, who in turn had less activity compared to HC youth. Covarying for depression severity replicated all results except the third finding; in this subsequent analysis, a Group by Self interaction showed that although HC had similar midline cortical structure (MCS) activity for all faces, LS showed higher MCS activity for the self vs. other faces while HS showed the opposite pattern. Results suggest that the neurophysiology of emotionally charged self-referential information can distinguish depressed, suicidal youth versus non-suicidal depressed and healthy adolescents. Neurophysiological differences and implications for the prediction of suicidality in youth are discussed. General Scientific Summary: Depressed adolescents with high suicidality show less activity in brain areas that support emotional experiences and self-awareness when identifying their own face, suggesting that abnormal self-processing may be associated with greater suicide risk. PMID:27618278

Large-scale brain networks are distinctly affected in right and left mesial temporal lobe epilepsy.

PubMed

de Campos, Brunno Machado; Coan, Ana Carolina; Lin Yasuda, Clarissa; Casseb, Raphael Fernandes; Cendes, Fernando

2016-09-01

Mesial temporal lobe epilepsy (MTLE) with hippocampus sclerosis (HS) is associated with functional and structural alterations extending beyond the temporal regions and abnormal pattern of brain resting state networks (RSNs) connectivity. We hypothesized that the interaction of large-scale RSNs is differently affected in patients with right- and left-MTLE with HS compared to controls. We aimed to determine and characterize these alterations through the analysis of 12 RSNs, functionally parceled in 70 regions of interest (ROIs), from resting-state functional-MRIs of 99 subjects (52 controls, 26 right- and 21 left-MTLE patients with HS). Image preprocessing and statistical analysis were performed using UF(2) C-toolbox, which provided ROI-wise results for intranetwork and internetwork connectivity. Intranetwork abnormalities were observed in the dorsal default mode network (DMN) in both groups of patients and in the posterior salience network in right-MTLE. Both groups showed abnormal correlation between the dorsal-DMN and the posterior salience, as well as between the dorsal-DMN and the executive-control network. Patients with left-MTLE also showed reduced correlation between the dorsal-DMN and visuospatial network and increased correlation between bilateral thalamus and the posterior salience network. The ipsilateral hippocampus stood out as a central area of abnormalities. Alterations on left-MTLE expressed a low cluster coefficient, whereas the altered connections on right-MTLE showed low cluster coefficient in the DMN but high in the posterior salience regions. Both right- and left-MTLE patients with HS have widespread abnormal interactions of large-scale brain networks; however, all parameters evaluated indicate that left-MTLE has a more intricate bihemispheric dysfunction compared to right-MTLE. Hum Brain Mapp 37:3137-3152, 2016. © 2016 The Authors Human Brain Mapping Published by Wiley Periodicals, Inc. © 2016 The Authors Human Brain Mapping Published by Wiley Periodicals, Inc.

Longitudinal positron emission tomography imaging of glial cell activation in a mouse model of mesial temporal lobe epilepsy: Toward identification of optimal treatment windows.

PubMed

Nguyen, Duc-Loc; Wimberley, Catriona; Truillet, Charles; Jego, Benoit; Caillé, Fabien; Pottier, Géraldine; Boisgard, Raphaël; Buvat, Irène; Bouilleret, Viviane

2018-06-01

Mesiotemporal lobe epilepsy is the most common type of drug-resistant partial epilepsy, with a specific history that often begins with status epilepticus due to various neurological insults followed by a silent period. During this period, before the first seizure occurs, a specific lesion develops, described as unilateral hippocampal sclerosis (HS). It is still challenging to determine which drugs, administered at which time point, will be most effective during the formation of this epileptic process. Neuroinflammation plays an important role in pathophysiological mechanisms in epilepsy, and therefore brain inflammation biomarkers such as translocator protein 18 kDa (TSPO) can be potent epilepsy biomarkers. TSPO is associated with reactive astrocytes and microglia. A unilateral intrahippocampal kainate injection mouse model can reproduce the defining features of human temporal lobe epilepsy with unilateral HS and the pattern of chronic pharmacoresistant temporal seizures. We hypothesized that longitudinal imaging using TSPO positron emission tomography (PET) with 18 F-DPA-714 could identify optimal treatment windows in a mouse model during the formation of HS. The model was induced into the right dorsal hippocampus of male C57/Bl6 mice. Micro-PET/computed tomographic scanning was performed before model induction and along the development of the HS at 7 days, 14 days, 1 month, and 6 months. In vitro autoradiography and immunohistofluorescence were performed on additional mice at each time point. TSPO PET uptake reached peak at 7 days and mostly related to microglial activation, whereas after 14 days, reactive astrocytes were shown to be the main cells expressing TSPO, reflected by a continuing increased PET uptake. TSPO-targeted PET is a highly potent longitudinal biomarker of epilepsy and could be of interest to determine the therapeutic windows in epilepsy and to monitor response to treatment. Wiley Periodicals, Inc. © 2018 International League Against Epilepsy.

Socioeconomic status, cognition, and hippocampal sclerosis.

PubMed

Baxendale, Sallie; Heaney, Dominic

2011-01-01

Poorer surgical outcomes in patients with low socioeconomic status have previously been reported, but the mechanisms underlying this pattern are unknown. Lower socioeconomic status may be a proxy marker for the limited economic opportunities associated with compromised cognitive function. The aim of this study was to examine the preoperative neuropsychological characteristics of patients with unilateral hippocampal sclerosis (HS) and their relationship to socioeconomic status. Two hundred ninety-two patients with medically intractable temporal lobe epilepsy and unilateral HS completed tests of memory and intellectual function prior to surgery. One hundred thirty-one had right HS (RHS), and 161 had left HS (LHS). The socioeconomic status of each participant was determined via the Index of Multiple Deprivation (IMD) associated with their postcode. The IMD was not associated with age at the time of assessment, age at onset of epilepsy, or duration of active epilepsy. The RHS and LHS groups did not differ on the IMD. The IMD was negatively correlated with all neuropsychological test scores in the LHS group. In the RHS group, the IMD was not significantly correlated with any of the neuropsychological measures. There were no significant correlations in the RHS group. Regression analyses suggested that IMD score explained 3% of variance in the measures of intellect, but 8% of the variance in verbal learning in the LHS group. The IMD explained 1% or less of the variance in neuropsychological scores in the RHS group. Controlling for overall level of intellectual function, the IMD score explained a small but significant proportion of the variance in verbal learning in the LHS group and visual learning for the RHS group. Our findings suggest that patients living in an area with a high IMD enter surgery with greater focal deficits associated with their epilepsy and more widespread cognitive deficits if they have LHS. Further work is needed to establish the direction of the relationship between low socioeconomic status and the neurocognitive sequelae of epilepsy. Copyright © 2010 Elsevier Inc. All rights reserved.

Modulatory effect of betaine on expression dynamics of HSPs during heat stress acclimation in goat (Capra hircus).

PubMed

Dangi, Satyaveer Singh; Dangi, Saroj K; Chouhan, V S; Verma, M R; Kumar, Puneet; Singh, Gyanendra; Sarkar, Mihir

2016-01-10

Changing climatic scenario with expected global rise in surface temperature compelled more focus of research over decoding heat stress response mechanism of animals and mitigation of heat stress. Recently betaine, a trimethyl form of glycine has been found to ameliorate heat stress in some species of animals. To overcome deleterious effect of heat stress, an attempt was taken to investigate the effect of betaine supplementation on heat stress mitigation in goats. Eighteen female Barbari goats were taken and randomly divided into 3 groups (n=6) such as control, HS (Heat stressed), HS+B (Heat stressed administered with betaine). Except for the control group, other groups were exposed to repeated heat stress (42 °C) for 6 h for sixteen consecutive days. Blood samples were collected at the end of heat exposure on day 1 (Initial heat stress acclimation - IHSA), day 6 (Short term heat stress acclimation - STHSA) and day 16 (Long term heat stress acclimation - LTHSA). When the groups were compared between different heat stress acclimatory phases, expression of all HSPs (HSP60, HSP70, HSP90 and HSP105/110) showed a similar pattern with a first peak on IHSA, reaching a basal level on STHSA followed by second peak on LTHSA. The messenger RNA (mRNA) and protein expression of HSPs was observed to be higher (P<0.05) in HS group than HS+B group except HSP90 on IHSA and HSP60 on STHSA. HSP105/110 expression was highest (P<0.05) on LTHSA. Immunocytochemical analysis revealed that HSPs were mainly localized both in nucleus and cytoplasm of PBMCs. In conclusion, heat stress increases HSPs expression and betaine administration was shown to have a dwindling effect on expression of HSPs, suggesting a possible role of this chemical chaperone on heat stress amelioration. Copyright © 2015 Elsevier B.V. All rights reserved.

[hsCRP protein in children and adolescents with diabetes type 1].

PubMed

Głowińska-Olszewska, Barbara; Urban, Mirosława; Peczyńska, Jadwiga; Koput, Alicja

2007-01-01

HsCRP protein is known as a novel marker of low grade inflammatory state, which characterises an atherosclerotic process in its early stages. Contrary to a large amount of data on inflammatory markers in diabetes type 2 and metabolic syndrome in adults, little is known so far about the inflammatory process in diabetes type 1, especially in children. The aim of the study was to estimate the level of hsCRP protein in children and adolescents with diabetes type 1 depending on coexisting additional risk factors for atherosclerosis and microvascular complications. 127 children and adolescents with diabetes duration 6.7+/-3.3 years, aged 14.9+/-3.1, were studied. The control group consisted of 52 healthy children aged 14.9+/-2.8 years, matched acc. to gender. HsCRP level was assessed with use of immunoturbidymetric, latex augmented method (Tina-quant CRP (Latex) HS, Roche). HsCRP in the whole study group was nearly significantly higher compared to control group: 0.17+/-0.2 vs. 0.078+/-0.1 mg/dl, p=0.072. In diabetic hypertensive children (n=38) we found significantly higher levels of hsCRP compared to controls (0.27+/-0.3 vs. 0.07 mg/dl, p=0.008) and compared to diabetic normotensive children (0.13+/-0.22 mg/dl; p=0.024). Diabetic obese patients (n=23) had significantly higer hsCRP compared to controls (0.24+/-0.3 vs. 0.07+/-0.1 mg/dl, p=0.04). In 14 studied diabetic children we found coexisting hypertension and obesity, and we found further increase in hsCRP level - 0.28+/-0.3 mg/dl. In diabetic children with microangiopathy hsCRP level was 0.22+/-0.2 mg/dl, and it was insignificantly higher compared to controls and to diabetic children without complications. Correlation analysis showed interrelations between hsCRP and systolic blood pressure (r=0.2; p=0.04) and HbA1c (r=0.25; p=0.015). In stepwise regression analysis hsCRP was related to systolic blood pressure, HbA1c and the triglycerides level (R=0.37; p=0.003). In children and adolescents with diabetes type 1 we proved significantly higher levels of hsCRP in case of a coexistence of hypertension and/or obesity. Elevated hsCRP in children with diabetes type 1 and hypertension and/or obesity reflects low grade inflammatory state in the course of metabolic syndrome.

Does a higher metal oxidation state necessarily imply higher reactivity toward H-atom transfer? A computational study of C-H bond oxidation by high-valent iron-oxo and -nitrido complexes.

PubMed

Geng, Caiyun; Ye, Shengfa; Neese, Frank

2014-04-28

In this work, the reactions of C-H bond activation by two series of iron-oxo ( (Fe(IV)), (Fe(V)), (Fe(VI))) and -nitrido model complexes ( (Fe(IV)), (Fe(V)), (Fe(VI))) with a nearly identical coordination geometry but varying iron oxidation states ranging from iv to vi were comprehensively investigated using density functional theory. We found that in a distorted octahedral coordination environment, the iron-oxo species and their isoelectronic nitrido analogues feature totally different intrinsic reactivities toward C-H bond cleavage. In the case of the iron-oxo complexes, the reaction barrier monotonically decreases as the iron oxidation state increases, consistent with the gradually enhanced electrophilicity across the series. The iron-nitrido complex is less reactive than its isoelectronic iron-oxo species, and more interestingly, a counterintuitive reactivity pattern was observed, i.e. the activation barriers essentially remain constant independent of the iron oxidation states. The detailed analysis using the Polanyi principle demonstrates that the different reactivities between these two series originate from the distinct thermodynamic driving forces, more specifically, the bond dissociation energies (BDEE-Hs, E = O, N) of the nascent E-H bonds in the FeE-H products. Further decomposition of the BDEE-Hs into the electron and proton affinity components shed light on how the oxidation states modulate the BDEE-Hs of the two series.

Pattern recognition and genetic algorithms for discrimination of orange juices and reduction of significant components from headspace solid-phase microextraction.

PubMed

Rinaldi, Maurizio; Gindro, Roberto; Barbeni, Massimo; Allegrone, Gianna

2009-01-01

Orange (Citrus sinensis L.) juice comprises a complex mixture of volatile components that are difficult to identify and quantify. Classification and discrimination of the varieties on the basis of the volatile composition could help to guarantee the quality of a juice and to detect possible adulteration of the product. To provide information on the amounts of volatile constituents in fresh-squeezed juices from four orange cultivars and to establish suitable discrimination rules to differentiate orange juices using new chemometric approaches. Fresh juices of four orange cultivars were analysed by headspace solid-phase microextraction (HS-SPME) coupled with GC-MS. Principal component analysis, linear discriminant analysis and heuristic methods, such as neural networks, allowed clustering of the data from HS-SPME analysis while genetic algorithms addressed the problem of data reduction. To check the quality of the results the chemometric techniques were also evaluated on a sample. Thirty volatile compounds were identified by HS-SPME and GC-MS analyses and their relative amounts calculated. Differences in composition of orange juice volatile components were observed. The chosen orange cultivars could be discriminated using neural networks, genetic relocation algorithms and linear discriminant analysis. Genetic algorithms applied to the data were also able to detect the most significant compounds. SPME is a useful technique to investigate orange juice volatile composition and a flexible chemometric approach is able to correctly separate the juices.

The AhR and NF-κB/Rel Proteins Mediate the Inhibitory Effect of 2,3,7,8-Tetrachlorodibenzo-p-Dioxin on the 3′ Immunoglobulin Heavy Chain Regulatory Region

PubMed Central

Salisbury, Richard L.; Sulentic, Courtney E. W.

2015-01-01

Transcriptional regulation of the murine immunoglobulin (Ig) heavy chain gene (Igh) involves several regulatory elements including the 3′Igh regulatory region (3′IghRR), which is composed of at least 4 enhancers (hs3A, hs1.2, hs3B, and hs4). The hs1.2 and hs4 enhancers exhibit the greatest transcriptional activity and contain binding sites for several transcription factors including nuclear factor kappaB/Rel (NF-κB/Rel) proteins and the aryl hydrocarbon receptor (AhR). Interestingly, the environmental immunosuppressant 2,3,7,8-tetrachlorodibenzo-p-dioxin (TCDD), which potently inhibits antibody secretion, also profoundly inhibits 3′IghRR and hs1.2 enhancer activation induced by the B-lymphocyte activator lipopolysaccharide (LPS), but enhances LPS-induced activation of the hs4 enhancer. Within the hs1.2 and hs4 enhancers, the AhR binding site is in close proximity or overlaps an NF-κB/Rel binding site suggesting a potential reciprocal modulation of the 3′IghRR by AhR and NF-κB/Rel. The objective of the current study was to evaluate the role of NF-κB/Rel and the AhR on the 3′IghRR and its enhancers using the AhR ligand TCDD, the AhR antagonist CH223191, and toll-like receptor agonists LPS, Resiquimod (R848), or cytosine-phosphate-guanine-oligodeoxynucleotides (CpG). Utilizing the CH12.LX B-lymphocyte cell line and variants expressing either a 3′IghRR-regulated transgene reporter or an inducible IκBα (inhibitor kappa B-alpha protein) superrepressor (IκBαAA), we demonstrate an AhR- and NF-κB/Rel-dependent modulation of 3′IghRR and hs4 activity. Additionally, in mouse splenocytes or CH12.LX cells, binding within the hs1.2 and hs4 enhancer of the AhR and the NF-κB/Rel proteins RelA and RelB was differentially altered by the cotreatment of LPS and TCDD. These results suggest that the AhR and NF-κB/Rel protein binding profile within the 3′IghRR mediates the inhibitory effects of TCDD on Ig expression and therefore antibody levels. PMID:26377645

Four subunits that are shared by the three classes of RNA polymerase are functionally interchangeable between Homo sapiens and Saccharomyces cerevisiae.

PubMed Central

Shpakovski, G V; Acker, J; Wintzerith, M; Lacroix, J F; Thuriaux, P; Vigneron, M

1995-01-01

Four cDNAs encoding human polypeptides hRPB7.0, hRPB7.6, hRPB17, and hRPB14.4 (referred to as Hs10 alpha, Hs10 beta, Hs8, and Hs6, respectively), homologous to the ABC10 alpha, ABC10 beta, ABC14.5, and ABC23 RNA polymerase subunits (referred to as Sc10 alpha, Sc10 beta, Sc8, and Sc6, respectively) of Saccharomyces cerevisiae, were cloned and characterized for their ability to complement defective yeast mutants. Hs10 alpha and the corresponding Sp10 alpha of Schizosaccharomyces pombe can complement an S. cerevisiae mutant (rpc10-delta::HIS3) defective in Sc10 alpha. The peptide sequences are highly conserved in their carboxy-terminal halves, with an invariant motif CX2CX12RCX2CGXR corresponding to a canonical zinc-binding domain. Hs10 beta, Sc10 beta, and the N subunit of archaeal RNA polymerase are homologous. An invariant CX2CGXnCCR motif presumably forms an atypical zinc-binding domain. Hs10 beta, but not the archaeal subunit, complemented an S. cerevisiae mutant (rpb10-delta 1::HIS3) lacking Sc10 beta. Hs8 complemented a yeast mutant (rpb8-delta 1::LYS2) defective in the corresponding Sc8 subunit, although with a strong thermosensitive phenotype. Interspecific complementation also occurred with Hs6 and with the corresponding Dm6 cDNA of Drosophila melanogaster. Hs6 cDNA and the Sp6 cDNA of S. pombe are dosage-dependent suppressors of rpo21-4, a mutation generating a slowly growing yeast defective in the largest subunit of RNA polymerase II. Finally, a doubly chimeric S. cerevisiae strain bearing the Sp6 cDNA and the human Hs10 beta cDNA was also viable. No interspecific complementation was observed for the human hRPB25 (Hs5) homolog of the yeast ABC27 (Sc5) subunit. PMID:7651387

Vagal nerve stimulation modulates the dendritic cell profile in posthemorrhagic shock mesenteric lymph.

PubMed

Morishita, Koji; Costantini, Todd W; Eliceiri, Brian; Bansal, Vishal; Coimbra, Raul

2014-03-01

Previous studies have established that posthemorrhagic shock mesenteric lymph (PHSML) contains proinflammatory mediators, while the cellular basis of PHSML is less well characterized in acute models of injury. CD103 dendritic cells (DCs) have been identified in the mesenteric lymph (ML) in models of chronic intestinal inflammation, suggesting an important role in the gut response to injury. We have previously demonstrated the ability of vagal nerve stimulation (VNS) to prevent gut barrier failure after trauma/hemorrhagic shock (T/HS); however, the ability of VNS to alter ML DCs is unknown. We hypothesized that the CD103 MHC-II DC population would change in PHSML and that VNS would prevent injury-induced changes in this population in PHSML. Male Sprague-Dawley rats were randomly assigned to trauma/sham shock or T/HS. T/HS was induced by midline laparotomy and 60 minutes of HS (blood pressure, 35 mm Hg), followed by fluid resuscitation. A separate cohort of animals underwent cervical VNS after the HS phase. Gut tissue was harvested at 2 hours after injury for histologic analysis. ML was collected during the pre-HS, HS, and post-HS phase. For flow cytometric analysis, ML cells were subjected to staining with CD103 and MHC-II antibodies, and this cell population was compared in the pre-HS and post-HS phase from the same animal. The CD4Foxp3 cell (T reg) population in the ML node (MLN) was also tested to determine effects of CD103 DC modulation in the ML. VNS reduced histologic gut injury and ML flow seen after injury. The CD103 MHC-II DC population in the PHSML was significantly decreased compared with pre-HS and was associated with decreased T reg expression in the MLN. VNS prevented the injury-induced decrease in the CD103 MHC-II+ DC population in the ML and restored the T reg population in the MLN. These findings suggest that VNS mediates the inflammatory responses in ML DCs and MLN T reg cells by affecting the set point of T/HS responsiveness.

Frequent Seizures Are Associated with a Network of Gray Matter Atrophy in Temporal Lobe Epilepsy with or without Hippocampal Sclerosis

PubMed Central

Coan, Ana C.; Campos, Brunno M.; Yasuda, Clarissa L.; Kubota, Bruno Y.; Bergo, Felipe PG.; Guerreiro, Carlos AM.; Cendes, Fernando

2014-01-01

Objective Patients with temporal lobe epilepsy (TLE) with hippocampal sclerosis (HS) have diffuse subtle gray matter (GM) atrophy detectable by MRI quantification analyses. However, it is not clear whether the etiology and seizure frequency are associated with this atrophy. We aimed to evaluate the occurrence of GM atrophy and the influence of seizure frequency in patients with TLE and either normal MRI (TLE-NL) or MRI signs of HS (TLE-HS). Methods We evaluated a group of 172 consecutive patients with unilateral TLE-HS or TLE-NL as defined by hippocampal volumetry and signal quantification (122 TLE-HS and 50 TLE-NL) plus a group of 82 healthy individuals. Voxel-based morphometry was performed with VBM8/SPM8 in 3T MRIs. Patients with up to three complex partial seizures and no generalized tonic-clonic seizures in the previous year were considered to have infrequent seizures. Those who did not fulfill these criteria were considered to have frequent seizures. Results Patients with TLE-HS had more pronounced GM atrophy, including the ipsilateral mesial temporal structures, temporal lobe, bilateral thalami and pre/post-central gyri. Patients with TLE-NL had more subtle GM atrophy, including the ipsilateral orbitofrontal cortex, bilateral thalami and pre/post-central gyri. Both TLE-HS and TLE-NL showed increased GM volume in the contralateral pons. TLE-HS patients with frequent seizures had more pronounced GM atrophy in extra-temporal regions than TLE-HS with infrequent seizures. Patients with TLE-NL and infrequent seizures had no detectable GM atrophy. In both TLE-HS and TLE-NL, the duration of epilepsy correlated with GM atrophy in extra-hippocampal regions. Conclusion Although a diffuse network GM atrophy occurs in both TLE-HS and TLE-NL, this is strikingly more evident in TLE-HS and in patients with frequent seizures. These findings suggest that neocortical atrophy in TLE is related to the ongoing seizures and epilepsy duration, while thalamic atrophy is more probably related to the original epileptogenic process. PMID:24475055

Force-Velocity and Power Characteristics of Rat Soleus Muscle Fibers after Hindlimb Suspension

NASA Technical Reports Server (NTRS)

McDonald, K. S.; Blaser, C. A.; Fitts, R. H.

1994-01-01

The effects of 1, 2, and 3 wk of Hindlimb Suspension (HS) on force-velocity and power characteristics of single rat soleus fibers were determined. After 1, 2, or 3 wk of HS, small fiber bundles were isolated, placed in skinning solution, and stored at -20 C until studied. Single fibers were isolated and placed between a motor arm and force transducer, functional properties were studied, and fiber protein content was subsequently analyzed by sodium dodecyl sulfate-polyacrylamide gel electrophoresis (SDS-PAGE). Additional fibers were isolated from soleus of control and after 1 and 3 wk of HS, and fiber type distribution and myosin light chain stoichiometry were determined from SDS-PAGE analysis. After 1 wk of HS, percent type I fibers declined from 82 to 74%, whereas hybrid fibers increased from 10 to 18%. Percent fast type 11 fibers increased from 8% in control and 1 wk of HS to 26% by 3 wk of HS. Most fibers showed an increased unloaded maximal shortening velocity (V(sub 0)), but myosin heavy chain remained entirely slow type I. The mechanism for increased V(sub 0) is unknown. There was a progressive decrease in fiber diameter (14, 30, and 38%) and peak force (38, 56, and 63%) after 1, 2, and 3 wk of HS, respectively. One week of HS resulted in a shift of the force-velocity curve, and between 2 and 3 wk of HS the curve shifted further such that V(sub 0) was higher than control at all relative loads less than 45% peak isometric force. Peak absolute power output of soleus fibers progressively decreased through 2 wk of HS but showed no further change at 3 wk. The results suggest that between 2 and 3 wk the HS-induced alterations in the force-velocity relationship act to maintain the power output of single soleus fibers despite a continued reduction in fiber force.

IL-6-Mediated Activation of Stat3α Prevents Trauma/Hemorrhagic Shock-Induced Liver Inflammation

PubMed Central

Moran, Ana; Thacker, Stephen A.; Arikan, Ayse Akcan; Mastrangelo, Mary-Ann A.; Wu, Yong; Yu, Bi; Tweardy, David J.

2011-01-01

Trauma complicated by hemorrhagic shock (T/HS) is the leading cause of morbidity and mortality in the United States for individuals under the age of 44 years. Initial survivors are susceptible to developing multiple organ failure (MOF), which is thought to be caused, at least in part, by excessive or maladaptive activation of inflammatory pathways. We previously demonstrated in rodents that T/HS results in liver injury that can be prevented by IL-6 administration at the start of resuscitation; however, the contribution of the severity of HS to the extent of liver injury, whether or not resuscitation is required, and the mechanism(s) for the IL-6 protective effect have not been reported. In the experiments described here, we demonstrated that the extent of liver inflammation induced by T/HS depends on the duration of hypotension and requires resuscitation. We established that IL-6 administration at the start of resuscitation is capable of completely reversing liver inflammation and is associated with increased Stat3 activation. Global assessment of the livers showed that the main effect of IL-6 was to normalize the T/HS-induced inflammation transcriptome. Pharmacological inhibition of Stat3 activity within the liver blocked the ability of IL-6 to prevent liver inflammation and to normalize the T/HS-induced liver inflammation transcriptome. Genetic deletion of a Stat3β, a naturally occurring, dominant-negative isoform of the Stat3, attenuated T/HS-induced liver inflammation, confirming a role for Stat3, especially Stat3α, in preventing T/HS-mediated liver inflammation. Thus, T/HS-induced liver inflammation depends on the duration of hypotension and requires resuscitation; IL-6 administration at the start of resuscitation reverses T/HS-induced liver inflammation, through activation of Stat3α, which normalized the T/HS-induced liver inflammation transcriptome. PMID:21738667

Hepatic steatosis and steatohepatitis in human immunodeficiency virus/hepatitis C virus-coinfected patients.

PubMed

Macías, Juan; Berenguer, Juan; Japón, Miguel A; Girón-González, José A; Rivero, Antonio; López-Cortés, Luis F; Moreno, Ana; Márquez, Manuel; Iribarren, José A; Ortega, Enrique; Miralles, Pilar; Merchante, Nicolás; Pineda, Juan A

2012-10-01

Hepatic steatosis (HS) is frequent in human immunodeficiency virus (HIV)- and hepatitis C virus (HCV)-coinfected patients. Antiretroviral therapy (ART) and metabolic alterations could induce HS. However, a protective effect of ART has been reported in a paired biopsy study. Thus, our aim was to examine the changes and predictors of HS progression among HIV/HCV-coinfected patients with sequential biopsies. We also evaluated the rates of steatohepatitis and factors associated thereof. HIV-infected patients with detectable serum HCV RNA, who underwent two biopsies, separated at least by 1 year, were included in this retrospective study. HS progression was defined as increase in one or more HS grades. The median (interquartile range) time between biopsies was 3.3 (2.0-5.2) years. Among 146 individuals, HS at baseline was observed in 86 (60%) patients and in 113 (77%) in the follow-up biopsy (P < 0.001). Progression of HS was observed in 60 (40%) patients. HS regressed in 11 (8%) patients. Factors associated with HS progression were changes in fasting plasma glucose (FPG) between biopsies (per 10 mg/dL increase; odds ratio [OR] [95% confidence interval; CI] = 1.4 [1.04-1.8]; P = 0.024) and cumulative use of dideoxynucleoside analogs (per year; OR [95% CI] = 1.5 [1.2-1.8]; P = 0.001). Persistent steatohepatitis or progression to steatohepatitis between biopsies was observed in 27 (18%) patients. Persistence of or progression to steatohepatitis was associated with progression ≥ 1 fibrosis stages between biopsies (OR [95% CI] = 2.4 [1.01-5.7]; P = 0.047). HS progresses frequently and regression is rarely observed in HIV/HCV-coinfected patients, including in those on ART. Cumulative exposure to dideoxynucleoside analogs and increases in FPG are related with HS progression. Stetatohepatitis is frequently observed in these patients and is linked to fibrosis progression. Copyright © 2012 American Association for the Study of Liver Diseases.

Non-hard sphere thermodynamic perturbation theory.

PubMed

Zhou, Shiqi

2011-08-21

A non-hard sphere (HS) perturbation scheme, recently advanced by the present author, is elaborated for several technical matters, which are key mathematical details for implementation of the non-HS perturbation scheme in a coupling parameter expansion (CPE) thermodynamic perturbation framework. NVT-Monte Carlo simulation is carried out for a generalized Lennard-Jones (LJ) 2n-n potential to obtain routine thermodynamic quantities such as excess internal energy, pressure, excess chemical potential, excess Helmholtz free energy, and excess constant volume heat capacity. Then, these new simulation data, and available simulation data in literatures about a hard core attractive Yukawa fluid and a Sutherland fluid, are used to test the non-HS CPE 3rd-order thermodynamic perturbation theory (TPT) and give a comparison between the non-HS CPE 3rd-order TPT and other theoretical approaches. It is indicated that the non-HS CPE 3rd-order TPT is superior to other traditional TPT such as van der Waals/HS (vdW/HS), perturbation theory 2 (PT2)/HS, and vdW/Yukawa (vdW/Y) theory or analytical equation of state such as mean spherical approximation (MSA)-equation of state and is at least comparable to several currently the most accurate Ornstein-Zernike integral equation theories. It is discovered that three technical issues, i.e., opening up new bridge function approximation for the reference potential, choosing proper reference potential, and/or using proper thermodynamic route for calculation of f(ex-ref), chiefly decide the quality of the non-HS CPE TPT. Considering that the non-HS perturbation scheme applies for a wide variety of model fluids, and its implementation in the CPE thermodynamic perturbation framework is amenable to high-order truncation, the non-HS CPE 3rd-order or higher order TPT will be more promising once the above-mentioned three technological advances are established. © 2011 American Institute of Physics

Epigenetic Inactivation of Heparan Sulfate (Glucosamine) 3-O-Sulfotransferase 2 in Lung Cancer and Its Role in Tumorigenesis

PubMed Central

Hwang, Jung-Ah; Kim, Yujin; Hong, Seung-Hyun; Lee, Jieun; Cho, Yong Gu; Han, Ji-Youn; Kim, Young-Ho; Han, Joungho; Shim, Young Mog; Lee, Yeon-Su; Kim, Duk-Hwan

2013-01-01

Background This study was aimed at investigating the functional significance of heparan sulfate (glucosamine) 3-O-sulfotransferase 2 (HS3ST2) hypermethylation in non-small cell lung cancer (NSCLC). Methodology/ Principal Findings HS3ST2 hypermethylation was characterized in six lung cancer cell lines, and its clinical significance was analyzed using 298 formalin-fixed paraffin-embedded tissues and 26 fresh-frozen tissues from 324 NSCLC patients. MS-HRM (methylation-specific high-resolution melting) and EpiTYPERTM assays showed substantial hypermethylation of CpG island at the promoter region of HS3ST2 in six lung cancer cell lines. The silenced gene was demethylated and re-expressed by treatment with 5-aza-2′-deoxycytidine (5-Aza-dC). A promoter assay also showed the core promoter activity of HS3ST2 was regulated by methylation. Exogenous expression of HS3ST2 in lung cancer cells H460 and H23 inhibited cell migration, invasion, cell proliferation and whereas knockdown of HS3ST2 in NHBE cells induced cell migration, invasion, and cell proliferation in vitro. A negative correlation was observed between mRNA and methylation levels of HS3ST2 in 26 fresh-frozen tumors tissues (ρ = -0.51, P = 0.009; Spearman’s rank correlation). HS3ST2 hypermethylation was found in 95 (32%) of 298 primary NSCLCs. Patients with HS3ST2 hypermethylation in 193 node-negative stage I-II NSCLCs with a median follow-up period of 5.8 years had poor overall survival (hazard ratio = 2.12, 95% confidence interval = 1.25–3.58, P = 0.005) compared to those without HS3ST2 hypermethylation, after adjusting for age, sex, tumor size, adjuvant therapy, recurrence, and differentiation. Conclusions/ Significance The present study suggests that HS3ST2 hypermethylation may be an independent prognostic indicator for overall survival in node-negative stage I-II NSCLC. PMID:24265783

Association of Elevated High Sensitivity Cardiac Troponin T(hs-cTnT) Levels with Hemorrhagic Transformation and 3-Month Mortality in Acute Ischemic Stroke Patients with Rheumatic Heart Disease in China

PubMed Central

Xiong, Yao; Liu, Bian; Hao, Zilong; Tao, Wendan; Liu, Ming

2016-01-01

Background and Objective Elevated levels of high sensitivity cardiac troponin T (hs-cTnT) occur in a substantial proportion of patients with acute ischemic stroke (AIS) and can predict poor outcome and mortality after stroke. Whether elevated hs-cTnT levels can also predict hemorrhagic transformation (HT) or prognosis in AIS patients with rheumatic heart disease (RHD) remains unclear. Methods Data from the Chengdu Stroke Registry on consecutive AIS patients with RHD admitted to West China Hospital within1 month of stroke onset from October 2011 to February 2014 were examined. Clinico-demographic characteristics, HT, functional outcomes and stroke recurrence were compared between patients with elevated hs-cTnT levels(≥14ng/L) and patients with normal hs-cTnT levels (<14ng/L). Results The final analysis involved 84 patients (31 males; mean age, 61.6±12.2years), of whom serum hs-cTnT levels were elevated in 58.3%. Renal impairment was independently associated with elevated hs-cTnT levels (OR 4.184, 95%CI 1.17 to 15.01, P = 0.028), and patients with elevated hs-cTnT levels were at significantly higher risk of HT, 3-month mortality and 3-month disability/mortality (all P≤0.029). After controlling for age, sex, hypertension, renal impairment and National Institutes of Health Stroke Scale score on admission, the risk of HT and 3-month mortality was, respectively, 4.0- and 5.5-fold higher in patients with elevated hs-cTnT levels than in patients with normal hs-cTnT levels. Conclusion Elevated hs-cTnT levels are independently associated with HT and 3-month mortality in AIS patients with RHD. These results with a small cohort should be verified and extended in large studies. PMID:26849554

Association of Elevated High Sensitivity Cardiac Troponin T(hs-cTnT) Levels with Hemorrhagic Transformation and 3-Month Mortality in Acute Ischemic Stroke Patients with Rheumatic Heart Disease in China.

PubMed

Liu, Junfeng; Wang, Deren; Xiong, Yao; Liu, Bian; Hao, Zilong; Tao, Wendan; Liu, Ming

2016-01-01

Elevated levels of high sensitivity cardiac troponin T (hs-cTnT) occur in a substantial proportion of patients with acute ischemic stroke (AIS) and can predict poor outcome and mortality after stroke. Whether elevated hs-cTnT levels can also predict hemorrhagic transformation (HT) or prognosis in AIS patients with rheumatic heart disease (RHD) remains unclear. Data from the Chengdu Stroke Registry on consecutive AIS patients with RHD admitted to West China Hospital within 1 month of stroke onset from October 2011 to February 2014 were examined. Clinico-demographic characteristics, HT, functional outcomes and stroke recurrence were compared between patients with elevated hs-cTnT levels (≥14 ng/L) and patients with normal hs-cTnT levels (<14 ng/L). The final analysis involved 84 patients (31 males; mean age, 61.6±12.2 years), of whom serum hs-cTnT levels were elevated in 58.3%. Renal impairment was independently associated with elevated hs-cTnT levels (OR 4.184, 95%CI 1.17 to 15.01, P = 0.028), and patients with elevated hs-cTnT levels were at significantly higher risk of HT, 3-month mortality and 3-month disability/mortality (all P≤0.029). After controlling for age, sex, hypertension, renal impairment and National Institutes of Health Stroke Scale score on admission, the risk of HT and 3-month mortality was, respectively, 4.0- and 5.5-fold higher in patients with elevated hs-cTnT levels than in patients with normal hs-cTnT levels. Elevated hs-cTnT levels are independently associated with HT and 3-month mortality in AIS patients with RHD. These results with a small cohort should be verified and extended in large studies.

DFT/TD-DFT study on the electronic and spectroscopic properties of hollow cubic and hollow spherical (ZnO) m quantum dots interacting with CO, NO2 and SO3 molecules

NASA Astrophysics Data System (ADS)

Gopalakrishnan, Sankarasubramanian; Shankar, Ramasamy; Kolandaivel, Ponmalai

2018-03-01

Hollow spherical (HS) and hollow cubic (HC) (ZnO) m quantum dots (QDs) were constructed and optimized using density functional theory (DFT) method. CO, NO2 and SO3 molecules were used to interact with the HC and HS (ZnO) m QDs at the centre and on the surface of the QDs. The changes in the electronic energy levels of HC and HS (ZnO) m QDs due to the interactions of CO, NO2 and SO3 molecules have been studied. The electronic and spectroscopic properties, such as density of states, HOMO-LUMO energy gap, absorption spectra, IR and Raman spectra of HC and HS (ZnO) m QDs have been studied using DFT and Time dependent-DFT (TD-DFT) methods. The interaction energy values show that the SO3 molecule has strongly interacted with HC and HS (ZnO) m QDs than the CO and NO2 molecules. The results of the density of states show that the HC QDs have peaks that are very close to each other, whereas the same is found to be broad in the HS QDs. The HOMO-LUMO energy gap is more for the HS QDs than the HC QDs, and also it gets decreased, when the NO2 and SO3 molecules interact at the centre of the HC and HS (ZnO) m QDs. The blue and red shifts were observed in the absorption spectra of HS and HC QDs. The natural transition orbital (NTO) plot reveals that the interaction of the molecules on the surface of the QDs reduce the chance of electron-hole recombination; hence the energy gap increases for NO2 and SO3 molecular interactions on the surface of the HC and HS (ZnO) m QDs. The vibrational assignments have been made for HC and HS QDs interacting with CO, NO2 and SO3 molecules.

External validation of heart-type fatty acid binding protein, high-sensitivity cardiac troponin, and electrocardiography as rule-out for acute myocardial infarction.

PubMed

Van Hise, Christopher B; Greenslade, Jaimi H; Parsonage, William; Than, Martin; Young, Joanna; Cullen, Louise

2018-02-01

To externally validate a clinical decision rule incorporating heart fatty acid binding protein (h-FABP), high-sensitivity troponin (hs-cTn) and electrocardiogram (ECG) for the detection of acute myocardial infarction (AMI) on presentation to the Emergency Department. We also investigated whether this clinical decision rule improved identification of AMI over algorithms incorporating hs-cTn and ECG only. This study included data from 789 patients from the Brisbane ADAPT cohort and 441 patients from the Christchurch TIMI RCT cohort. The primary outcome was index AMI. Sensitivity, specificity, positive predictive value and negative predictive value were used to assess the diagnostic accuracy of the algorithms. 1230 patients were recruited, including 112 (9.1%) with AMI. The algorithm including h-FABP and hs-cTnT had 100% sensitivity and 32.4% specificity. The algorithm utilising h-FABP and hs-cTnI had similar sensitivity (99.1%) and higher specificity (43.4%). The hs-cTnI and hs-cTnT algorithms without h-FABP both had a sensitivity of 98.2%; a result that was not significantly different from either algorithm incorporating h-FABP. Specificity was higher for the hs-cTnI algorithm (68.1%) compared to the hs-cTnT algorithm (33.0%). The specificity of the algorithm incorporating hs-cTnI alone was also significantly higher than both of the algorithms incorporating h-FABP (p<0.01). For patients presenting to the Emergency Department with chest pain, an algorithm incorporating h-FABP, hs-cTn and ECG has high accuracy and can rule out up to 40% of patients. An algorithm incorporating only hs-cTn and ECG has similar sensitivity and may rule out a higher proportion of patients. Each of the algorithms can be used to safely identify patients as low risk for AMI on presentation to the Emergency Department. Copyright © 2017 The Canadian Society of Clinical Chemists. All rights reserved.

Average Amount and Stability of Available Agro-Climate Resources in the Main Maize Cropping Regions in China during 1981-2010

NASA Astrophysics Data System (ADS)

Zhao, Jin; Yang, Xiaoguang

2018-02-01

The available agro-climate resources that can be absorbed and converted into dry matter could directly affect crop growth and yield under climate change. Knowledge of the average amount and stability of available agro-climate resources for maize in the main cropping regions of China under climate change is essential for farmers and advisors to optimize cropping choices and develop adaptation strategies under limited resources. In this study, the three main maize cropping regions in China—the North China spring maize region (NCS), the Huanghuaihai summer maize region (HS), and the Southwest China mountain maize region (SCM)—were selected as study regions. Based on observed solar radiation, temperature, and precipitation data, we analyzed the spatial distributions and temporal trends in the available agro-climate resources for maize during 1981-2010. During this period, significantly prolonged climatological growing seasons for maize [3.3, 2.0, and 4.7 day (10 yr)-1 in NCS, HS, and SCM] were found in all three regions. However, the spatiotemporal patterns of the available agro-climate resources differed among the three regions. The available heating resources for maize increased significantly in the three regions, and the rates of increase were higher in NCS [95.5°C day (10 yr)-1] and SCM [93.5°C day (10 yr)-1] than that in HS [57.7°C day (10 yr)-1]. Meanwhile, decreasing trends in the available water resources were found in NCS [-5.3 mm (10 yr)-1] and SCM [-5.8 mm (10 yr)-1], whereas an increasing trend was observed in HS [3.0 mm (10 yr)-1]. Increasing trends in the available radiation resources were found in NCS [20.9 MJ m-2 (10 yr)-1] and SCM [25.2 MJ m-2 (10 yr)-1], whereas a decreasing trend was found in HS [11.6 MJ m-2 (10 yr)-1]. Compared with 1981-90, the stability of all three resource types decreased during 1991-2000 and 2001-10 in the three regions. More consideration should be placed on the extreme events caused by more intense climate fluctuations. The results can provide guidance in the development of suitable adaptations to climate change in the main maize cropping regions in China.

Optimizing fluorescently tethered Hsp90 inhibitor dose for maximal specific uptake by breast tumors

NASA Astrophysics Data System (ADS)

Crouch, Brian T.; Duer, Joy; Wang, Roujia; Gallagher, Jennifer; Hall, Allison; Soo, Mary Scott; Hughes, Philip; Haystead, Timothy A. J.; Ramanujam, Nirmala

2018-03-01

Despite improvements in surgical resection, 20-40% of patients undergoing breast conserving surgery require at least one additional re-excision. Leveraging the unique surface expression of heat shock protein 90 (Hsp90), a chaperone protein involved in several key hallmarks of cancer, in breast cancer provides an exciting opportunity to identify residual disease during surgery. We developed a completely non-destructive strategy using HS-27, a fluorescently-tethered Hsp90 inhibitor, to assay surface Hsp90 expression on intact tissue specimens using a fluorescence microendoscope with a field of view of 750 μm and subcellular resolution of 4 μm. HS-27 consists of an FDA approved Hsp90 inhibitor tethered to fluorescein isothiocyanate (EX 488nm, EM 525nm). Here, we optimized ex vivo HS-27 administration in pre-clinical breast cancer models and validated our approach on 21 patients undergoing standard of care ultrasound guided core needle biopsy. HS-27 administration time was fixed at 1- minute to minimize imaging impact on clinical workflow. HS-27 and HS-217 (non-specific control) doses were modulated from 1 μM up to 100 μM to identify the dose maximizing the ratio of specific uptake (HS-27 fluorescence) to non-specific uptake (HS-217 fluorescence). The specificity ratio was maximized at 100 μM and was significantly greater than all other doses (p<0.05). We applied our optimized imaging protocol to clinical samples and demonstrated significantly greater uptake of HS-27 by tumor than non-tumor tissue (p<0.05). The ubiquitous nature of HS-27 binding to all subtypes of breast cancer makes this technology attractive for assessing tumor margins, as one agent can be used for all subtypes.

Comparison of Healthcare Costs Among Commercially Insured Women in the United States Who Underwent Hysteroscopic Sterilization Versus Laparoscopic Bilateral Tubal Ligation Sterilization.

PubMed

Carney, Patricia I; Yao, Jianying; Lin, Jay; Law, Amy

2017-05-01

This study evaluated healthcare costs of index procedures and during a 6-month follow-up of women who had hysteroscopic sterilization (HS) versus laparoscopic bilateral tubal ligation (LBTL). Women (18-49 years) with claims for HS and LBTL procedures were identified from the MarketScan commercial claims database (January 1, 2010, to December 31, 2012) and placed into separate cohorts. Demographics, characteristics, index procedure costs, and 6-month total healthcare costs and sterilization procedure-related costs were compared. Multivariable regression analyses were used to examine the impact of HS versus LBTL on costs. Among the study population, 12,031 had HS (mean age: 37.0 years) and 7286 had LBTL (mean age: 35.8 years). The majority (80.9%) who had HS underwent the procedure in a physician's office setting. Fewer women who had HS versus LBTL received the procedure in an inpatient setting (0.5% vs. 2.1%), an ambulatory surgical center setting (5.0% vs. 23.8%), or a hospital outpatient setting (13.4% vs. 71.9%). Mean total cost for the index sterilization procedure was lower for HS than for LBTL ($3964 vs. $5163, p < 0.0001). During the 6-month follow-up, total medical and prescription costs for all causes ($7093 vs. $7568, p < 0.0001) and sterilization procedure-related costs ($4971 vs. $5407, p < 0.0001) were lower for women who had HS versus LBTL. Multivariable regression results confirmed that costs were lower for women who had HS versus LBTL. Among commercially insured women in the United States, HS versus LBTL is associated with lower average costs for the index procedure and lower total healthcare and procedure-related costs during 6 months after the sterilization procedure.

Newborn screening for mucopolysaccharidoses: A pilot study of measurement of glycosaminoglycans by tandem mass spectrometry

PubMed Central

Kubaski, Francyne; Mason, Robert W.; Nakatomi, Akiko; Shintaku, Haruo; Xie, Li; van Vlies, Naomi N.; Church, Heather; Giugliani, Roberto; Kobayashi, Hironori; Yamaguchi, Seiji; Suzuki, Yasuyuki; Orii, Tadao; Fukao, Toshiyuki; Montaño, Adriana M.; Tomatsu, Shunji

2016-01-01

BACKGROUND Mucopolysaccharidoses (MPS) are a group of inborn errors of metabolism that are progressive and usually result in irreversible in skeletal, visceral and/or brain damage, highlighting a need for early diagnosis. METHODS This pilot study analyzed 2,862 dried blood spots (DBS) from newborns and 14 DBS from newborn patients with MPS (MPS I, n = 7; MPS II, n = 2; MPS III, n = 5). Disaccharides were produced from polymer GAGs by digestion with chondroitinase B, heparitinase, and keratanase II. Heparan sulfate (0S, NS), dermatan sulfate (DS) and mono- and di-sulfated KS were measured by liquid chromatography tandem mass spectrometry (LC-MS/MS). Median absolute deviation (MAD) was used to determine cutoffs to distinguish patients from controls. Cutoffs were defined as median + 7× MAD from general newborns. RESULTS The cutoffs were as follows: HS-0S> 90ng/mL; HS-NS> 23 ng/mL, DS> 88 ng/mL; mono-sulfated KS> 445 ng/mL; di-sulfated KS> 89 ng/mL and ratio di-KS in total KS> 32%. All MPS I and II samples were above the cutoffs for HS-0S, HS-NS and DS, and all MPS III samples were above cutoffs for HS-0S and HS-NS. The rate of false positives for MPS I and II was 0.03% based on a combination of HS-0S, HS-NS, and DS, and for MPS III was 0.9% based upon a combination of HS-0S and HS-NS. CONCLUSIONS Combination of levels of two or more different GAGs improves separation of MPS patients from unaffected controls, indicating that GAG measurements are potentially valuable biomarkers for newborn screening for MPS. PMID:27718145

Spin and orbital states in single-layered La2-xCaxCoO4 studied by doping- and temperature-dependent near-edge x-ray absorption fine structure

NASA Astrophysics Data System (ADS)

Merz, M.; Fuchs, D.; Assmann, A.; Uebe, S.; v. Löhneysen, H.; Nagel, P.; Schuppler, S.

2011-07-01

The doping-dependent valence, orbital, and spin-state configurations of single-layered La2-xCaxCoO4 (x=0, 0.5, 1, and 1.5) were investigated with temperature-dependent near-edge x-ray absorption fine structure at the Co L2,3 and O K edges. The spectra show that in La2CoO4, the superexchange between neighboring Co2+ HS states is responsible for the strong antiferromagnetism. With increasing hole doping, the superexchange interactions between Co2+ HS ions are rapidly reduced by interlaced nonmagnetic Co3+ LS. For La1.5Ca0.5CoO4, the low Néel temperature of the samples together with the 50% Co2+ HS and 50% Co3+ LS configuration suggests a checkerboard arrangement of these ions. The spin blockade resulting from this arrangement naturally explains the high resistivity of La1.5Ca0.5CoO4. Upon further doping, Co2+ HS ions are replaced by Co3+ HS, and for LaCaCoO4 a mixture of Co3+ LS and Co3+ HS occurs. Superexchange via configuration fluctuation processes between these two species seems to induce long-range ferromagnetism, while the superexchange between adjacent Co3+ HS neighbors may lead to a competing antiferromagnetic exchange. For a doping content beyond x=1, Co4+ HS is introduced to the system at the expense of Co3+ LS, and a t2g double exchange between Co3+ HS and Co4+ HS is established, which further enhances ferromagnetic interactions and reduces resistivity. No indications for a Co3+ IS state are found throughout the La2-xCaxCoO4 doping series.

Anti-Pigmentation Effects of Eight Phellinus linteus-Fermented Traditional Crude Herbal Extracts on Brown Guinea Pigs of Ultraviolet B-Induced Hyperpigmentation.

PubMed

Ahn, Hee-Young; Choo, Young-Moo; Cho, Young-Su

2018-03-28

We have previously found that mycelia culture broth of eight kinds of traditional herbal extracts fermented with Phellinus linteus (previously named as 8-HsPLCB) not only inhibited melanin and tyrosinase activity, but also reduced the contents of melanogenesis-related proteins, including tyrosinase and microphthalmia-associated transcription factor, in 3-isobutyl-1-methylxanthine-stimulated B16F0 melanoma cells. For a further study, the effect of 8-HsPLCB against skin pigmentation in brown guinea pigs with ultraviolet B (UVB)-induced hyperpigmentation was investigated. 8-HsPLCB (3%) and arbutin (2%) as positive controls were applied topically twice daily for 4 weeks to the hyperpigmented areas. 8-HsPLCB showed skin-lightening effect as effective as arbutin, one of the most widely used in whitening cosmetics. Melanin index values as the degree of pigmentation showed a significant reduction week by week post 8-HsPLCB treatment and then substantially reduced by 4 weeks. The degree of depigmentation after 4 weeks of topical application with 8-HsPLCB was 32.2% as compared with before treatment (0 week). Moreover, using Fontana-Masson staining and hematoxylin-eosin staining, 8-HsPLCB reduced melanin pigmentation in the basal layer of the epidermis and epidermal thickness changes exposed to the UV-B irradiation as compared with non-treatment and vehicle treatment. The intensity of the skin-lightening effect of 8-HsPLCB was similar to arbutin. These results suggest that the skin-lightening effect of 8-HsPLCB might be resulted from inhibition of melanin synthesis by tyrosinase in melanocytes. To conclude, 8-HsPLCB treatment showed reduction of the melanin pigment and histological changes induced by UV irradiation in brown guinea pigs.

The role of histopathologic subtype in the setting of hippocampal sclerosis-associated mesial temporal lobe epilepsy.

PubMed

Gales, Jordan M; Jehi, Lara; Nowacki, Amy; Prayson, Richard A

2017-05-01

Hippocampal sclerosis (HS) and focal cortical dysplasia (FCD) are among the most common neuropathological findings in those undergoing surgery for refractory mesial temporal lobe epilepsy. Existing data regarding differences among the most recent International League Against Epilepsy (ILAE) HS subtypes remain limited. This study sought to characterize the roles of HS subtype and coexistent FCD. Epilepsy surgery pathologic specimens in 307 cases of temporal lobe epilepsy with HS were reviewed (mean age±SD, 37±15years; 56% women). HS and coexistent FCD were classified according to ILAE guidelines. Medical records were reviewed for data on seizure recurrence and seizure burden (clinical follow-up mean duration ± SD, 5±4years). Cases of typical HS (ILAE type I) predominated (ILAE type Ia: 41%, Ib: 47%, II: 11%, and III: 0.7%]. The HS subtypes shared similar demographic and etiologic characteristics, as well as associated pathology and postoperative seizure outcomes. Individuals with type Ib HS were more likely to remain seizure free at long-term follow-up when compared with other subtypes, and they had a later age of seizure onset. Two hundred forty-three cases (79%) demonstrated FCD within the adjacent temporal lobe. Its presence was associated with a significantly decreased risk of seizure recurrence (P=.02). When present, FCD was predominantly type I (98%). HS subtype does not appear to affect epilepsy surgery outcomes despite some clinical differences between the subgroups. FCD is often observed in association with HS in mesial temporal lobe epilepsy; the finding of FCD was associated with better postoperative outcomes. Copyright © 2017 Elsevier Inc. All rights reserved.

Newborn screening for mucopolysaccharidoses: a pilot study of measurement of glycosaminoglycans by tandem mass spectrometry.

PubMed

Kubaski, Francyne; Mason, Robert W; Nakatomi, Akiko; Shintaku, Haruo; Xie, Li; van Vlies, Naomi N; Church, Heather; Giugliani, Roberto; Kobayashi, Hironori; Yamaguchi, Seiji; Suzuki, Yasuyuki; Orii, Tadao; Fukao, Toshiyuki; Montaño, Adriana M; Tomatsu, Shunji

2017-01-01

Mucopolysaccharidoses (MPS) are a group of inborn errors of metabolism that are progressive and usually result in irreversible skeletal, visceral, and/or brain damage, highlighting a need for early diagnosis. This pilot study analyzed 2862 dried blood spots (DBS) from newborns and 14 DBS from newborn patients with MPS (MPS I, n = 7; MPS II, n = 2; MPS III, n = 5). Disaccharides were produced from polymer GAGs by digestion with chondroitinase B, heparitinase, and keratanase II. Heparan sulfate (0S, NS), dermatan sulfate (DS) and mono- and di-sulfated KS were measured by liquid chromatography tandem mass spectrometry (LC-MS/MS). Median absolute deviation (MAD) was used to determine cutoffs to distinguish patients from controls. Cutoffs were defined as median + 7× MAD from general newborns. The cutoffs were as follows: HS-0S > 90 ng/mL; HS-NS > 23 ng/mL, DS > 88 ng/mL; mono-sulfated KS > 445 ng/mL; di-sulfated KS > 89 ng/mL and ratio di-KS in total KS > 32 %. All MPS I and II samples were above the cutoffs for HS-0S, HS-NS, and DS, and all MPS III samples were above cutoffs for HS-0S and HS-NS. The rate of false positives for MPS I and II was 0.03 % based on a combination of HS-0S, HS-NS, and DS, and for MPS III was 0.9 % based upon a combination of HS-0S and HS-NS. Combination of levels of two or more different GAGs improves separation of MPS patients from unaffected controls, indicating that GAG measurements are potentially valuable biomarkers for newborn screening for MPS.

Deletion of the human beta-globin LCR 5'HS4 or 5'HS1 differentially affects beta-like globin gene expression in beta-YAC transgenic mice.

PubMed

Fedosyuk, Halyna; Peterson, Kenneth R

2007-01-01

A 213 kb human beta-globin locus yeast artificial chromosome (beta-YAC) was modified by homologous recombination to delete 2.9 kb of cross-species conserved sequence similarity encompassing the LCR 5' hypersensitive site (HS) 4 (Delta5'HS4 beta-YAC). In three transgenic mouse lines, completion of the gamma- to beta-globin switch during definitive erythropoiesis was delayed relative to wild-type beta-YAC mice. In addition, quantitative per-copy human beta-like globin mRNA levels were similar to wild-type beta-YAC transgenic lines, although beta-globin gene expression was slightly decreased in the day 12 fetal liver of Delta5'HS4 beta-YAC mice. A 0.8 kb 5'HS1 fragment was similarly deleted in the YAC. Three Delta5'HS1 beta-YAC transgenic lines were established. epsilon-globin gene expression was markedly reduced, approximately 16 fold, during primitive erythropoiesis compared to wild-type beta-YAC mice, but gamma-globin expression levels were unaffected. However, during the fetal stage of definitive erythropoiesis, gamma-globin gene expression was decreased approximately 4 fold at day 12 and approximately 5 fold at day 14. Temporal developmental expression profiles of the beta-like globin genes were unaffected by deletion of 5'HS1. Decreased expression of the epsilon- and gamma-globin genes is the first phenotype ascribed to a 5'HS1 mutation in the human beta-globin locus, suggesting that this HS does indeed have a role in LCR function beyond simply a combined synergism with the other LCR HSs.

Half-squat or jump squat training under optimum power load conditions to counteract power and speed decrements in Brazilian elite soccer players during the preseason.

PubMed

Loturco, Irineu; Pereira, Lucas A; Kobal, Ronaldo; Zanetti, Vinicius; Gil, Saulo; Kitamura, Katia; Abad, Cesar Cavinato Cal; Nakamura, Fabio Y

2015-01-01

The purpose of this study was to test which specific type of exercise (i.e., jump squat (JS) or half-squat (HS)) is more effective at maintaining speed and power abilities throughout a preseason in soccer players. Twenty-three male soccer players were randomly allocated into two groups: JS and HS. The mean propulsive power, vertical jumping ability, and sprinting performance were evaluated before and after 4 weeks of a preseason period. The optimum power loads for the JS and HS exercises were assessed and were used as load-references. The soccer players performed 10 power oriented training sessions in total. Both JS and HS maintained power in JS and speed abilities (P > 0.05, for main effects and interaction effect) as indicated by ANCOVA. Both groups demonstrated reduced power during HS (ES = -0.76 vs. -0.78, for JS and HS, respectively); both groups improved acceleration (ACC) from 5 to 10 m (ES = 0.52). JS was more effective at reducing the ACC decrements over 0-5 m (ES = -0.38 vs. -0.58, for JS and HS, respectively). The HS group increased squat jump height (ES = 0.76 vs. 0.11, for HS and JS, respectively). In summary, JS is more effective in reducing the ACC capacity over very short sprints while HS is more effective in improving squat jump performance. Both strategies improve ACC over longer distances. New training strategies should be implemented/developed to avoid concurrent training effects between power and endurance adaptations during professional soccer preseasons.

Temporal proteomic response to acute heat stress in the porcine muscle sarcoplasm.

PubMed

Cruzen, S M; Baumgard, L H; Gabler, N K; Pearce, S C; Lonergan, S M

2017-09-01

Heat stress (HS) is an important topic in the swine industry, costing hundreds of millions of dollars in economic losses annually, figures that could easily rise in light of global climate change. Muscle biology during HS is particularly important given skeletal muscle's large proportion to the body and its ultimate conversion to meat. Here we report the proteomic changes that occur during acute HS (37°C and 40% relative humidity) lasting 2, 4, or 6 h in the muscle sarcoplasm of growing pigs in comparison with 6 h of thermal neutral (TN; 21°C and 70% relative humidity) conditions ( = 8 per treatment). The red and white areas of the semitendinosus muscle were used to compare the differential effects of HS on oxidative or glycolytic muscles. The results support the hypothesis of proteomic profile differences between the acute HS and TN groups. Altered abundance ( < 0.05) of several proteins occurred in as little as 2 h of HS, affecting metabolism, cell structure, and chaperone, antioxidant, and proteolytic activity. We determined that the muscle HS response is both fiber type and time specific. Overall, more differences were observed in the red semitendinosus than in the white semitendinosus, although the time point at which differences were observed varied. These data show that as little as 2 h of HS has measurable effects on muscle proteins, indicating that acute HS has the potential to impair muscle function and growth.

Fractone-heparan sulphates mediate FGF-2 stimulation of cell proliferation in the adult subventricular zone.

PubMed

Douet, V; Kerever, A; Arikawa-Hirasawa, E; Mercier, F

2013-04-01

Fractones are extracellular matrix structures that form a niche for neural stem cells and their immediate progeny in the subventricular zone of the lateral ventricle (SVZa), the primary neurogenic zone in the adult brain. We have previously shown that heparan sulphates (HS) associated with fractones bind fibroblast growth factor-2 (FGF-2), a powerful mitotic growth factor in the SVZa. Here, our objective was to determine whether the binding of FGF-2 to fractone-HS is implicated in the mechanism leading to cell proliferation in the SVZa. Heparitinase-1 was intracerebroventricularly injected with FGF-2 to N-desulfate HS proteoglycans and determine whether the loss of HS and of FGF-2 binding to fractones modifies FGF-2 effect on cell proliferation. We also examined in vivo the binding of Alexa-Fluor-FGF-2 in relationship with the location of HS immunoreactivity in the SVZa. Heparatinase-1 drastically reduced the stimulatory effect of FGF-2 on cell proliferation in the SVZa. Alexa-Fluor-FGF-2 binding was strictly co-localized with HS immunoreactivity in fractones and adjacent vascular basement membranes in the SVZa. Our results demonstrate that FGF-2 requires HS to stimulate cell proliferation in the SVZa and suggest that HS associated with fractones and vascular basement membranes are responsible for activating FGF-2. Therefore, fractones and vascular basement membranes may function as a HS niche to drive cell proliferation in the adult neurogenic zone. © 2013 Blackwell Publishing Ltd.

How divergent conceptions among health and education stakeholders influence the dissemination of healthy schools in Quebec.

PubMed

Deschesnes, Marthe; Couturier, Yves; Laberge, Suzanne; Campeau, Louise

2010-12-01

This paper focuses on dissemination of the healthy schools (HS) approach in the province of Quebec, Canada. Dissemination aims at raising awareness about HS and promoting its adhesion among actors concerned with youth health in school. As HS is a joint initiative based on agreement and collaboration between health and educational sectors, the positions of stakeholders that foster cooperation between these sectors were considered to be critical to optimize its dissemination. The study's objectives were to: (i) examine and contrast the stakeholders' conceptions of HS and (ii) understand how converging and diverging stakeholders' positions on HS favourably or negatively influence its dissemination in Quebec. Gray's analytical approach to collaboration and its focus on stakeholders' mindframe about a domain served as a conceptual lens to examine stakeholders' positions regarding HS. Collection methods included documentary analysis and semi-structured interviews of 34 key internal and external informants at the provincial, regional and local levels. The results showed consensual adhesion to fundamental principles of the HS approach. However, differences in conceptualization between provincial authorities of the two sectors concerning the way to disseminate HS have been observed. These differences represented a significant barrier to HS optimal dissemination. A dialogue between the two authorities appears to be essential to arrive at a negotiated and shared conceptualization of this issue in the Quebec context, thus allowing agreements for adequate support. The results may serve as the basis for a more fruitful dialogue between actors from the two sectors, at different administrative levels.

Aspirin upregulates αB-Crystallin to protect the myocardium against heat stress in broiler chickens

PubMed Central

Tang, Shu; Yin, Bin; Song, Erbao; Chen, Hongbo; Cheng, Yanfen; Zhang, Xiaohui; Bao, Endong; Hartung, Joerg

2016-01-01

We established in vivo and in vitro models to investigate the role of αB-Crystallin (CryAB) and assess the ability of aspirin (ASA) to protect the myocardium during prolonged heat stress. Thirty-day-old chickens were divided into three groups (n = 90): heat stress (HS, 40±1 °C); ASA(−)HS(+), 1 mg/kg ASA orally 2 h before heat stress; and ASA(+)HS(−), pretreated with aspirin, no heat stress (25 °C). Hearts were excised after 0, 1, 2, 3, 5, 7, 10, 15 and 24 h. Heat stress increased body temperature, though the ASA(−)HS(+) group had significantly higher temperatures than the ASA(+)HS(+) group at all time points. Compared to ASA(+)HS(+), the ASA(−)HS(+) group displayed increased sensitivity to heat stress. Pathological analysis revealed the ASA (+)HS(+) myocardium showed less severe changes (narrowed, chaotic fibers; fewer necrotic cells) than the ASA(−)HS(+) group (bleeding and extensive cell death). In vitro, ASA-pretreatment significantly increased primary chicken myocardial cell survival during heat stress. ELISAs indicated ASA induced CryAB in vivo to protect against heat stress-induced myocardial damage, but ASA did not induce CryAB in primary chicken myocardial cells. The mechanisms by which ASA induces the expression of CryAB in vivo and protects the myocardium during heat stress merit further research. PMID:27857180

Oligosaccharide Substrate Preferences of Human Extracellular Sulfatase Sulf2 Using Liquid Chromatography-Mass Spectrometry Based Glycomics Approaches

PubMed Central

Huang, Yu; Mao, Yang; Buczek-Thomas, Jo Ann; Nugent, Matthew A.; Zaia, Joseph

2014-01-01

Sulfs are extracellular endosulfatases that selectively remove the 6-O-sulfate groups from cell surface heparan sulfate (HS) chain. By altering the sulfation at these particular sites, Sulfs function to remodel HS chains. As a result of the remodeling activity, HSulf2 regulates a multitude of cell-signaling events that depend on interactions between proteins and HS. Previous efforts to characterize the substrate specificity of human Sulfs (HSulfs) focused on the analysis of HS disaccharides and synthetic repeating units. In this study, we characterized the substrate preferences of human HSulf2 using HS oligosaccharides with various lengths and sulfation degrees from several naturally occurring HS sources by applying liquid chromatography mass spectrometry based glycomics methods. The results showed that HSulf2 preferentially digests highly sulfated HS oligosaccharides with zero acetyl groups and this preference is length dependent. In terms of length of oligosaccharides, HSulf2 digestion induced more sulfation decrease on DP6 (DP: degree of polymerization) compared to DP2, DP4 and DP8. In addition, the HSulf2 preferentially digests the oligosaccharide domain located at the non-reducing end (NRE) of the HS and heparin chain. In addition, the HSulf2 digestion products were altered only for specific isomers. HSulf2 treated NRE oligosaccharides also showed greater decrease in cell proliferation than those from internal domains of the HS chain. After further chromatographic separation, we identified the three most preferred unsaturated hexasaccharide for HSulf2. PMID:25127119

Effect of liver steatosis in outcome after bile duct reconstruction for iatrogenic injury.

PubMed

Mercado Díaz, Miguel Angel; Marcué, Miguel Urencio; Ramírez Del Val, Fernando; Domínguez Rosado, Ismael

2010-01-01

The estimated prevalence of nonalcoholic fatty liver disease (NAFLD) in the overall population is 30%. Bile duct injuries associated with cholecystectomy have a constant frequency and some patients with these types of injuries have concomitant hepatic stenosis (HS). It has not been determined if HS has a negative outcome on the results of surgical bile duct repair. Among a cohort of patients surgically repaired for bile duct injury, we selected those from whom a liver biopsy was obtained. Patients were divided into the following groups: group I--HS, group II--without HS. The groups were compared for long-term results of the reconstruction, postoperative complications, liver function test and need for reintervention. From group I we obtained 18 patients and from group II 71 patients. In 11% of the HS group and in 10% of the non-HS group anastomosis dysfunction was observed. Three cases in group I (17%) and 11 patients in group II (15.5%) needed further surgical reintervention. Complete rehabilitation was obtained in 77% of the cases in group I and 66% of patients in group II. No statistical differences were found in any features between groups. Patients with HS have a higher incidence of gallstone disease than the general population; hence, an increased probability of having a bile duct injury. The results of surgical reconstruction after these injuries are similar to those of patients without HS. Analyzed data showed no repercussion in outcome of patients with HS.

Hand sanitizer and rates of acute illness in military aviation personnel.

PubMed

Van Camp, Roscoe O; Ortega, Hernando J

2007-02-01

Alcohol-based hand sanitizer (HS) kills most organisms that cause acute illness, an important cause of lost duty time among aviation personnel. This preliminary study observed the impact on the acute illness rate when HS was made readily accessible to pilots. Wall-mounted HS dispensers were placed in two fighter squadron operations buildings during November 2005 and various media were used to alert all base personnel to the importance of hand hygiene and cough hygiene. Data were obtained for two groups of personnel on the same base: 1) pilots who worked in the two HS-equipped buildings (Squadron) (n = 56); and 2) pilots and air traffic controllers who worked at other locations (Non-Squadron) (n = 61). The incidence of acute illness and the cumulative number of duty days lost was determined in each group for the winters of 2004-05 (no HS) and 2005-06 (HS available). For the Squadron group, the acute illness rates were 2.4% in 2004-5 (210 duty days lost) (no HS) compared with 0.9% in 2005-6 (78 duty days lost) when HS was provided. No year-to-year difference was apparent for the Non-Squadron group, where the illness rates were 2.4% in 2004-5 (229 duty days lost) and 2.3% in 2005-6 (221 duty days lost). Making HS readily available at locations frequented by pilots together with educating them regarding hand hygiene may reduce the occurrence of acute illness and number of duty days lost.

Automated headspace solid-phase dynamic extraction to analyse the volatile fraction of food matrices.

PubMed

Bicchi, Carlo; Cordero, Chiara; Liberto, Erica; Rubiolo, Patrizia; Sgorbini, Barbara

2004-01-23

High concentration capacity headspace techniques (headspace solid-phase microextraction (HS-SPME) and headspace sorptive extraction (HSSE)) are a bridge between static and dynamic headspace, since they give high concentration factors as does dynamic headspace (D-HS), and are as easy to apply and as reproducible as static headspace (S-HS). In 2000, Chromtech (Idstein, Germany) introduced an inside-needle technique for vapour and liquid sampling, solid-phase dynamic extraction (SPDE), also known as "the magic needle". In SPDE, analytes are concentrated on a 50 microm film of polydimethylsiloxane (PDMS) and activated carbon (10%) coated onto the inside wall of the stainless steel needle (5 cm) of a 2.5 ml gas tight syringe. When SPDE is used for headspace sampling (HS-SPDE), a fixed volume of the headspace of the sample under investigation is sucked up an appropriate number of times with the gas tight syringe and an analyte amount suitable for a reliable GC or GC-MS analysis accumulates in the polymer coating the needle wall. This article describes the preliminary results of both a study on the optimisation of sampling parameters conditioning HS-SPDE recovery, through the analysis of a standard mixture of highly volatile compounds (beta-pinene, isoamyl acetate and linalool) and of the HS-SPDE-GC-MS analyses of aromatic plants and food matrices. This study shows that HS-SPDE is a successful technique for HS-sampling with high concentration capability, good repeatability and intermediate precision, also when it is compared to HS-SPME.

LCR 5' hypersensitive site specificity for globin gene activation within the active chromatin hub.

PubMed

Peterson, Kenneth R; Fedosyuk, Halyna; Harju-Baker, Susanna

2012-12-01

The DNaseI hypersensitive sites (HSs) of the human β-globin locus control region (LCR) may function as part of an LCR holocomplex within a larger active chromatin hub (ACH). Differential activation of the globin genes during development may be controlled in part by preferential interaction of each gene with specific individual HSs during globin gene switching, a change in conformation of the LCR holocomplex, or both. To distinguish between these possibilities, human β-globin locus yeast artificial chromosome (β-YAC) lines were produced in which the ε-globin gene was replaced with a second marked β-globin gene (β(m)), coupled to an intact LCR, a 5'HS3 complete deletion (5'ΔHS3) or a 5'HS3 core deletion (5'ΔHS3c). The 5'ΔHS3c mice expressed β(m)-globin throughout development; γ-globin was co-expressed in the embryonic yolk sac, but not in the fetal liver; and wild-type β-globin was co-expressed in adult mice. Although the 5'HS3 core was not required for β(m)-globin expression, previous work showed that the 5'HS3 core is necessary for ε-globin expression during embryonic erythropoiesis. A similar phenotype was observed in 5'HS complete deletion mice, except β(m)-globin expression was higher during primitive erythropoiesis and γ-globin expression continued into fetal definitive erythropoiesis. These data support a site specificity model of LCR HS-globin gene interaction.

Camel whey protein protects lymphocytes from apoptosis via the PI3K/AKT, NF-κB, ATF-3 and HSP-70 signaling pathways in heat-stressed male mice.

PubMed

Badr, Gamal; Ramadan, Nancy K; Abdel-Tawab, Hanem S; Ahmed, Samia F; Mahmoud, Mohamed H

2017-11-22

Heat stress (HS) is an environmental factor that depresses the immune systems mediating dysfunctional immune cells. Camel whey protein (CWP) can scavenge free radicals and enhance immunity. The present study investigated the impact of dietary supplementation with CWP on immune dysfunction induced by exposure to HS. Male mice (n = 45) were divided into three groups: control group; HS group; and HS mice that were orally administered CWP (HS+CWP group). The HS group exhibited elevated levels of reactive oxygen species (ROS) and pro-inflammatory cytokines (IL-1β, IL-6, TNF-α) as well as a significant reduction in the IL-2 and IL-4 levels. Exposure to HS resulted in impaired AKT and IκB-α phosphorylation; increased ATF-3 and HSP70 expression; and aberrant distribution of CD3+ T cells and CD20+ B cells in the thymus and spleen. Interestingly, HS mice treated with CWP presented significantly restored levels of ROS and pro-inflammatory cytokines near the levels observed in control mice. Furthermore, supplementation of HS mice with CWP enhanced the phosphorylation of AKT and IκB-α; attenuated the expression of ATF-3, HSP70 and HSP90; and improved T and B cell distributions in the thymus and spleen. Our findings reveal a potential immunomodulatory effect of CWP in attenuating immune dysfunction induced by exposure to thermal stress.

Chemically Patterned Inverse Opal Created by a Selective Photolysis Modification Process.

PubMed

Tian, Tian; Gao, Ning; Gu, Chen; Li, Jian; Wang, Hui; Lan, Yue; Yin, Xianpeng; Li, Guangtao

2015-09-02

Anisotropic photonic crystal materials have long been pursued for their broad applications. A novel method for creating chemically patterned inverse opals is proposed here. The patterning technique is based on selective photolysis of a photolabile polymer together with postmodification on released amine groups. The patterning method allows regioselective modification within an inverse opal structure, taking advantage of selective chemical reaction. Moreover, combined with the unique signal self-reporting feature of the photonic crystal, the fabricated structure is capable of various applications, including gradient photonic bandgap and dynamic chemical patterns. The proposed method provides the ability to extend the structural and chemical complexity of the photonic crystal, as well as its potential applications.

Evaluation of the drug sensitivity and expression of 16 drug resistance-related genes in canine histiocytic sarcoma cell lines

PubMed Central

ASADA, Hajime; TOMIYASU, Hirotaka; GOTO-KOSHINO, Yuko; FUJINO, Yasuhito; OHNO, Koichi; TSUJIMOTO, Hajime

2015-01-01

Canine histiocytic sarcoma (HS) is an aggressive tumor type originating from histiocytic cell lineages. This disease is characterized by poor response to chemotherapy and short survival time. Therefore, it is of critical importance to identify and develop effective antitumor drugs against HS. The objectives of this study were to examine the drug sensitivities of 10 antitumor drugs. Using a real-time RT-PCR system, the mRNA expression levels of 16 genes related to drug resistance in 4 canine HS cell lines established from dogs with disseminated HS were determined and compared to 2 canine lymphoma cell lines (B-cell and T-cell). These 4 canine HS cell lines showed sensitivities toward microtubule inhibitors (vincristine, vinblastine and paclitaxel), comparable to those in the canine B-cell lymphoma cell line. Moreover, it was shown that P-gp in the HS cell lines used in this study did not have enough function to efflux its substrate. Sensitivities to melphalan, nimustine, methotrexate, cytarabine, doxorubicin and etoposide were lower in the 4 HS cell lines than in the 2 canine lymphoma cell lines. The data obtained in this study using cultured cell lines could prove helpful in the developing of advanced and effective chemotherapies for treating dogs that are suffering from HS. PMID:25715778

Evaluation of the drug sensitivity and expression of 16 drug resistance-related genes in canine histiocytic sarcoma cell lines.

PubMed

Asada, Hajime; Tomiyasu, Hirotaka; Goto-Koshino, Yuko; Fujino, Yasuhito; Ohno, Koichi; Tsujimoto, Hajime

2015-06-01

Canine histiocytic sarcoma (HS) is an aggressive tumor type originating from histiocytic cell lineages. This disease is characterized by poor response to chemotherapy and short survival time. Therefore, it is of critical importance to identify and develop effective antitumor drugs against HS. The objectives of this study were to examine the drug sensitivities of 10 antitumor drugs. Using a real-time RT-PCR system, the mRNA expression levels of 16 genes related to drug resistance in 4 canine HS cell lines established from dogs with disseminated HS were determined and compared to 2 canine lymphoma cell lines (B-cell and T-cell). These 4 canine HS cell lines showed sensitivities toward microtubule inhibitors (vincristine, vinblastine and paclitaxel), comparable to those in the canine B-cell lymphoma cell line. Moreover, it was shown that P-gp in the HS cell lines used in this study did not have enough function to efflux its substrate. Sensitivities to melphalan, nimustine, methotrexate, cytarabine, doxorubicin and etoposide were lower in the 4 HS cell lines than in the 2 canine lymphoma cell lines. The data obtained in this study using cultured cell lines could prove helpful in the developing of advanced and effective chemotherapies for treating dogs that are suffering from HS.

Effects of molecular composition of natural organic matter on ferric iron complexation at circumneutral pH.

PubMed

Fujii, Manabu; Imaoka, Akira; Yoshimura, Chihiro; Waite, T D

2014-04-15

Thermodynamic and kinetic parameters for ferric iron (Fe[III]) complexation by well-characterized humic substances (HS) from various origins were determined by a competitive ligand method with 5-sulfosalicylic acid at circumneutral pH (6.0-8.0) and an ionic strength of ∼0.06 M. The measured Fe binding properties including conditional stability constants and complexation capacities ranged over more than 2 orders of magnitude, depending on the origin and the particular operationally defined fraction of HS examined. Statistical comparison of the complexation parameters to a range of chemical properties of the HS indicated a strong positive correlation between Fe(III) complexation capacity and aromatic carbon content in the HS at all pHs examined. In contrast, the complexation capacity was determined to be up to a few orders of magnitude smaller than the concentration of carboxylic and phenolic groups present. Therefore, specific functional groups including those resident in the proximity of aromatic structures within the HS are likely preferable for Fe(III) coordination under the conditions examined. Overall, our results suggest that the concentration of dissolved Fe(III) complexes in natural waters is substantially influenced by variation in HS characteristics in addition to other well-known factors such as HS concentration and nature and concentration of competing cations present.

Neuroanatomical Differences between Men and Women in Help-Seeking Coping Strategy

PubMed Central

Li, Hai-Jiang; Sun, Jiang-Zhou; Zhang, Qing-Lin; Wei, Dong-Tao; Li, Wen-Fu; Jackson, Todd; Hitchman, Glenn; Qiu, Jiang

2014-01-01

Help seeking (HS) is a core coping strategy that is directed towards obtaining support, advice, or assistance as means of managing stress. Women have been found to use more HS than men. Neural correlates of sex differences have also been reported in prefrontal-limbic system (PLS) regions that are linked to stress and coping, yet structural differences between men and women relating to HS in the PLS are still unknown. Thus, the association between gray matter volume (GMV) and HS was investigated using voxel-based morphometry (VBM) in a large healthy sample (126 men and 156 women). Results indicated women reported more HS than men did. VBM results showed that the relation between HS scores and GMV differed between men and women in regions of the bilateral orbitofrontal cortex extending to the subgenual anterior cingulate cortex(OFC/sgACC). Among women, higher HS scores were associated with smaller GMV in these areas while a positive correlation between GMV and HS scores was observed among men. These results remained significant after controlling for general intelligence, stress, anxiety and depression. Thus, this study suggested that structural differences between men and women are correlated to characteristic brain regions known to be involved in the PLS which is considered critical in stress regulation. PMID:25027617

Propagation of classical swine fever virus in vitro circumventing heparan sulfate-adaptation.

PubMed

Eymann-Häni, Rita; Leifer, Immanuel; McCullough, Kenneth C; Summerfield, Artur; Ruggli, Nicolas

2011-09-01

Amplification of natural virus isolates in permanent cell lines can result in adaptation, in particular enhanced binding to heparan sulfate (HS)-containing glycosaminoglycans present on most vertebrate cells. This has been reported for several viruses, including the pestivirus classical swine fever virus (CSFV), the causative agent of a highly contagious hemorrhagic disease in pigs. Propagation of CSFV in cell culture is essential in virus diagnostics and research. Adaptation of CSFV to HS-binding has been related to amino acid changes in the viral E(rns) glycoprotein, resulting in viruses with altered replication characteristics in vitro and in vivo. Consequently, a compound blocking the HS-containing structures on cell surfaces was employed to monitor conversion from HS-independency to HS-dependency. It was shown that the porcine PEDSV.15 cell line permitted propagation of CSFV within a limited number of passages without adaptation to HS-binding. The selection of HS-dependent CSFV mutants was also prevented by propagation of the virus in the presence of DSTP 27. The importance of these findings can be seen from the altered ratio of cell-associated to secreted virus upon acquisition of enhanced HS-binding affinity, a phenotype proposed previously to be related to virulence in the natural host. Copyright © 2011 Elsevier B.V. All rights reserved.

Quercetin supplemented diet improves follicular development, oocyte quality, and reduces ovarian apoptosis in rabbits during summer heat stress.

PubMed

Naseer, Zahid; Ahmad, Ejaz; Epikmen, Erkmen Tuğrul; Uçan, Uğur; Boyacioğlu, Murat; İpek, Emrah; Akosy, Melih

2017-07-01

The present study was designed to test the modulatory effect of dietary quercetin on follicle population, apoptosis, in vitro maturation rate and quality of oocytes in heat stressed female rabbits. A total of thirty-four New Zealand White heat stress (HS) exposed female rabbits were either fed with quercetin supplemented diet (QU-HS) or non-supplemented (HS) diet. Firstly, laparotomy was performed for oocyte retrieval and then, oocyte grading and COCs dimensional assessments were conducted. The A and B-grade oocytes were submitted for in vitro maturation. Thereafter, the ovaries were collected from rabbits and were processed for follicular population estimation and granulosa cells apoptosis. The results showed that follicle number, retrieved oocytes and A-grade oocytes were higher in QU-HS, comparatively. A significant difference was observed in A-grade oocytes dimensions between QU-HS and HS treatment groups. The oocyte maturation rate was same across the groups. The quercetin supplementation significantly improved primordial and antral stage follicles. A greater number of apoptotic cells were observed in primary and antral follicles in the HS group. In conclusion, the quercetin provision improves the follicular development, minimize granulosa cells apoptosis, and maintain the oocyte competence in HS rabbits. Copyright © 2017. Published by Elsevier Inc.

Structure-Property Relationships in W Doped (Ba,Sr)TiO(3) Thin Films Deposited by Pulsed Laser Deposition on (001) MgO

DTIC Science & Technology

2003-04-03

vacancies. The lattice of an oxygen * Permanent address - Nuclear Research Center- Negev (NRCN), Beer Sheva 9001, Israel. 41 deficient perovskite film...the film were determined by analysis of x-ray diffraction pattern using Cu K,, radiation from a Rigaku rotating anode source and a powder...thank Dr. H.S Kim, Mr. R.C.Y. Auyeung, Office of Naval Research, DARPA FAME and Nuclear Research Center- Negev . REFERENCES 1. J.S. Horwitz, D.B

Perspectives on improvement of reproduction in cattle during heat stress in a future Japan.

PubMed

Kadokawa, Hiroya; Sakatani, Miki; Hansen, Peter J

2012-06-01

Heat stress (HS) causes hyperthermia, and at its most severe form, can lead to death. More commonly, HS reduces feed intake, milk yield, growth rate and reproductive function in many mammals and birds, including the important cattle breeds in Japan. Rectal temperatures greater than 39.0°C and respiration rates greater than 60/min indicate cows are undergoing HS sufficient to affect milk yield and fertility. HS compromises oocyte quality and embryonic development, reduces expression of estrus and changes secretion of several reproductive hormones. One of the most effective ways to reduce the magnitude of HS is embryo transfer, which bypasses the inhibitory effects of HS on the oocyte and early embryo. It may also be possible to select for genetic resistance to HS. Cooling can also improve reproductive performance in cows and heifers, and probably, the most effective cooling systems currently in use are those that couple evaporative cooling with tunnel ventilation or cross ventilation. Its effect on improving reproductive performance in Japan remains to be evaluated. © 2012 The Authors. Animal Science Journal © 2012 Japanese Society of Animal Science.

Relationship of HS CRP and Sacroiliac Joint Inflammation in Undifferentiated Spondyloarthritis.

PubMed

Liu, Te-Jung; Chang, Cheng-Chiang; Chen, Liang-Cheng; Chu, Heng-Yi; Hsu, Chun-Sheng; Chang, Shin-Tsu

2018-01-01

Elevation of serum high sensitivity C-reactive protein (hs-CRP) level has been demonstrated as a risk factor for varying diseases, as well as a biomarker for predicting recovery after operation of lumber disc herniation. Our objective was to investigate the relationship between serum hs-CRP and sacroiliac (SI) joint inflammation in patients with undifferentiated spondyloarthritis (uSpA). In this retrospective study, we enrolled patients with uSpA who underwent hs-CRP testing between January 2007 and September 2013. Serum hs-CRP was analyzed at our central laboratory. All enrolled patients underwent skeletal scintigraphic scan with quantitative sacroiliac measurement. A total of 29 patients were enrolled with mean age 32.27 years and female:male ratio of 6:23. Pearson's correlation coefficient showed a significant difference between hs-CRP in serum and SI/S ratio in uSpA, particularly the middle part of the sacroiliac joint, either right side or left side. The significantly high concentration of serum hs-CRP might indicate a systemic inflammatory response to flare-up of the SI joint and might be an indicator of SI inflammation in uSpA.

High salt intake does not exacerbate murine autoimmune thyroiditis

PubMed Central

Kolypetri, P; Randell, E; Van Vliet, B N; Carayanniotis, G

2014-01-01

Recent studies have shown that high salt (HS) intake exacerbates experimental autoimmune encephalomyelitis and have raised the possibility that a HS diet may comprise a risk factor for autoimmune diseases in general. In this report, we have examined whether a HS diet regimen could exacerbate murine autoimmune thyroiditis, including spontaneous autoimmune thyroiditis (SAT) in non-obese diabetic (NOD.H2h4) mice, experimental autoimmune thyroiditis (EAT) in C57BL/6J mice challenged with thyroglobulin (Tg) and EAT in CBA/J mice challenged with the Tg peptide (2549–2560). The physiological impact of HS intake was confirmed by enhanced water consumption and suppressed aldosterone levels in all strains. However, the HS treatment failed to significantly affect the incidence and severity of SAT or EAT or Tg-specific immunoglobulin (Ig)G levels, relative to control mice maintained on a normal salt diet. In three experimental models, these data demonstrate that HS intake does not exacerbate autoimmune thyroiditis, indicating that a HS diet is not a risk factor for all autoimmune diseases. PMID:24528002

High-Speed Ultra-High-Resolution Optical Coherence Tomography Findings in Hydroxychloroquine Retinopathy

PubMed Central

Rodriguez-Padilla, Julio A.; Hedges, Thomas R.; Monson, Bryan; Srinivasan, Vivek; Wojtkowski, Maciej; Reichel, Elias; Duker, Jay S.; Schuman, Joel S.; Fujimoto, James G.

2007-01-01

Objectives To compare structural changes in the retina seen on high-speed ultra–high-resolution optical coherence tomography (hsUHR-OCT) with multifocal electroretinography (mfERG) and automated visual fields in patients receiving hydroxychloroquine. Methods Fifteen patients receiving hydroxychloroquine were evaluated clinically with hsUHR-OCT, mfERG, and automated visual fields. Six age-matched subjects were imaged with hsUHR-OCT and served as controls. Results Distinctive discontinuity of the perifoveal photoreceptor inner segment/outer segment junction and thinning of the outer nuclear layer were seen with hsUHR-OCT in patients with mild retinal toxic effects. Progression to complete loss of the inner segment/outer segment junction and hyperscattering at the outer segment level were seen in more advanced cases. The mfERG abnormalities correlated with the hsUHR-OCT findings. Asymptomatic patients had normal hsUHR-OCT and mfERG results. Conclusion Distinctive abnormalities in the perifoveal photoreceptor inner segment/outer segment junction were seen on hsUHR-OCT in patients receiving hydroxychloroquine who also were symptomatic and had abnormalities on automated visual fields and mfERG. PMID:17562988

Effect of dasatinib in a xenograft mouse model of canine histiocytic sarcoma and in vitro expression status of its potential target EPHA2.

PubMed

Ito, K; Miyamoto, R; Tani, H; Kurita, S; Kobayashi, M; Tamura, K; Bonkobara, M

2018-02-01

Canine histiocytic sarcoma (HS) is an aggressive and highly metastatic tumor. Previously, the kinase inhibitor dasatinib was shown to have potent growth inhibitory activity against HS cells in vitro, possibly via targeting the EPHA2 receptor. Here, the in vivo effect of dasatinib in HS cells was investigated using a xenograft mouse model. Moreover, the expression status of EPHA2 was examined in six HS cell lines, ranging from insensitive to highly sensitive to dasatinib. In the HS xenograft mouse model, dasatinib significantly suppressed tumor growth, as illustrated by a decrease in mitotic and Ki67 indices and an increase in apoptotic index in tumor tissues. On Western blot analysis, EPHA2 was only weakly detected in all HS cell lines, regardless of sensitivity to dasatinib. Dasatinib likely results in the inhibition of xenograft tumor growth via a mechanism other than targeting EPHA2. The findings of this study suggest that dasatinib is a targeted therapy drug worthy of further exploration for the treatment of canine HS. © 2017 John Wiley & Sons Ltd.

Putting the Capital 'A' in CoCoRAHS: A Pilot Program to Measure Albedo using the Community Collaborative Rain, Hail, and Snow (CoCoRaHS) Network

NASA Astrophysics Data System (ADS)

Burakowski, E. A.; Stampone, M. D.; Wake, C. P.; Dibb, J. E.

2012-12-01

The Community Collaborative Rain, Hail, and Snow (CoCoRaHS) Network, started in 1998 as a community-based network of volunteer weather observer in Colorado, is the single largest provider of daily precipitation observations in the United States. We embrace the CoCoRaHS mission to use low-cost measurement tools, provide training and education, and utilize an interactive website to collect high quality albedo data for research and education applications. We trained a select sub-set of CoCoRaHS's eighteen most enthusiastic, self-proclaimed 'weather nuts' in the state of New Hampshire to collect surface albedo, snow depth, and snow density measurements between 23-Nov-2011 and 15-Mar-2012. At less than 700 per observer, the low-cost albedo data falls within ±0.05 of albedo values collected from a First Class Kipp and Zonen Albedometer (CMA6) at local solar noon. CoCoRaHS albedo values range from 0.99 for fresh snow to 0.34 for shallow, aged snow. Snow-free albedo ranges from 0.09 to 0.39, depending on ground cover. Albedo is found to increase logarithmically with snow depth and decrease linearly with snow density. The latter relationship with snow density is inferred to be a proxy for increasing snow grain size as snowpack ages and compacts, supported by spectral albedo measurements collected with an ASD FieldSpec4 spectrometer. The newly established albedo network also serves as a development test bed for interactive online mapping and graphing applications for CoCoRaHS observers to investigate spatial and temporal patterns in albedo, snow depth, and snow density (www.cocorahs-albedo.org). The 2012-2013 field season will include low-cost infrared temperature guns (<40 each) to investigate the relationship between surface albedo and skin temperature. We have also recruited middle- and high-schools as volunteer observers and are working with the teachers to develop curriculum and lesson plans that utilize the low-cost measurement tools provided by CoCoRAHS. CoCoRAHS data will provide critical spatially distributed measurements of surface data that will be used to validate and improve land surface modeling of New Hampshire climate under different land cover scenarios. Building on the success of the first season, the newly established albedo network shows promise to put the capital 'A' in CoCoRAHS.Figure 1. (a) Map of Community Collaborative Rain, Hail, and Snow (CoCoRAHS) volunteers participating in the pilot albedo project, and (b) CoCoRAHS snow measurement kit.

Six-Year Change in High-Sensitivity Cardiac Troponin T and Risk of Subsequent Coronary Heart Disease, Heart Failure, and Death.

PubMed

McEvoy, John W; Chen, Yuan; Ndumele, Chiadi E; Solomon, Scott D; Nambi, Vijay; Ballantyne, Christie M; Blumenthal, Roger S; Coresh, Josef; Selvin, Elizabeth

2016-08-01

High-sensitivity cardiac troponin T (hs-cTnT) is a biomarker of cardiovascular risk and could be approved in the United States for clinical use soon. However, data linking long-term temporal change in hs-cTnT to outcomes are limited, particularly in primary prevention settings. To examine the association of 6-year change in hs-cTnT with incident coronary heart disease (CHD), heart failure (HF), and all-cause mortality. This prospective observational cohort study, performed from January 1, 1990, to December 31, 2011, included 8838 participants with biracial representation from the Atherosclerosis Risk in Communities Study who were initially free of CHD and HF and who had hs-cTnT measured twice, 6 years apart. Data analysis was performed from October 28, 2014, to March 9, 2016. Risk factor and temporal hs-cTnT data were collected. Using Cox proportional hazards regression, we examined the association of hs-cTnT change with subsequent CHD, HF, and death during a maximum of 16 years. Improvement in discrimination was determined by the Harrell C statistic. Of the 8838 participants (mean age, 56 years; 5215 female [59.0%]; 1891 black [21.4%]) there were 1157 CHD events, 965 HF events, and 1813 deaths overall. Incident detectable hs-cTnT (baseline, <0.005 ng/mL; follow-up, ≥0.005 ng/mL) was independently associated with subsequent CHD (hazard ratio [HR], 1.4; 95% CI, 1.2-1.6), HF (HR, 2.0; 95% CI, 1.6-2.4), and death (HR, 1.5; 95% CI, 1.3-1.7), relative to an hs-cTnT level less than 0.005 ng/mL at both visits. In addition, HRs as high as 4 for CHD and death and 8 for HF were recorded among individuals with the most marked hs-cTnT increases (eg, baseline, < 0.005 ng/mL; follow-up, ≥0.014 ng/mL). Risk for subsequent outcomes was lower among those with relative hs-cTnT reductions greater than 50% from baseline. Furthermore, information on hs-cTnT change improved discrimination for HF and death when added to a model that included traditional risk factors, N-terminal pro-brain natriuretic peptide, and baseline hs-cTnT level. Among individuals with adjudicated HF hospitalizations, hs-cTnT change appeared to be similarly associated with HF with reduced and preserved ejection fraction. Temporal increases in hs-cTnT, suggestive of progressive myocardial damage, are independently associated with incident CHD, death, and, above all, HF. Serial determination of hs-cTnT trajectory adds clinically relevant information to baseline testing and may be useful in prognostic assessments and the targeting of prevention strategies to high-risk individuals, especially among persons with stage A or B HF.

Implementation of Hadamard spectroscopy using MOEMS as a coded aperture

NASA Astrophysics Data System (ADS)

Vasile, T.; Damian, V.; Coltuc, D.; Garoi, F.; Udrea, C.

2015-02-01

Although nowadays spectrometers reached a high level of performance, output signals are often weak and traditional slit spectrometers still confronts the problem of poor optical throughput, minimizing their efficiency in low light setup conditions. In order to overcome these issues, Hadamard Spectroscopy (HS) was implemented in a conventional Ebert Fastie type of spectrometer setup, by substituting the exit slit with a digital micro-mirror device (DMD) who acts like a coded aperture. The theory behind HS and the functionality of the DMD are presented. The improvements brought using HS are enlightened by means of a spectrometric experiment and higher SNR spectrum is acquired. Comparative experiments were conducted in order to emphasize the SNR differences between HS and scanning slit method. Results provide a SNR gain of 3.35 favoring HS. One can conclude the HS method effectiveness to be a great asset for low light spectrometric experiments.

Using mobile technology to improve healthcare service quality.

PubMed

Chao, Chia Chen; Jen, Wen Yuan; Li, Yu-Chuan; Chi, Y P; Chen, Chang-I; Feng, Chen Chjeh

2005-01-01

Improving healthcare service quality for illness of treatment, illness prevention and patient service is difficult for most hospitals because the hospitals are lack adequate resources and labor. In order to provide better healthcare service quality for patients, mobile technology can be used to manage healthcare in a way that provides the optimal healthcare service for patients. Pursuing utilization of mobile technology for better patient service, Taipei Medical University Municipal W. F. Teaching Hospital has implemented a mobile healthcare service (m-HS) system to increase healthcare service quality. The m-HS system improves the quality of medical care as well as healthcare service. The m-HS is a multi-functional healthcare management agent, meets the mobile tendency of the present society. This study seeks to discuss the m-HS architecture and workflow processes. We believe the m-HS does have the potential to improve healthcare service quality. Finally, the conclusions and suggestions for the m-HS are given.

The structure of human tripeptidyl peptidase II as determined by a hybrid approach.

PubMed

Schönegge, Anne-Marie; Villa, Elizabeth; Förster, Friedrich; Hegerl, Reiner; Peters, Jürgen; Baumeister, Wolfgang; Rockel, Beate

2012-04-04

Tripeptidyl-peptidase II (TPPII) is a high molecular mass (∼5 MDa) serine protease, which is thought to act downstream of the 26S proteasome, cleaving peptides released by the latter. Here, the structure of human TPPII (HsTPPII) has been determined to subnanometer resolution by cryoelectron microscopy and single-particle analysis. The complex is built from two strands forming a quasihelical structure harboring a complex system of inner cavities. HsTPPII particles exhibit some polymorphism resulting in complexes consisting of nine or of eight dimers per strand. To obtain deeper insights into the architecture and function of HsTPPII, we have created a pseudoatomic structure of the HsTPPII spindle using a comparative model of HsTPPII dimers and molecular dynamics flexible fitting. Analyses of the resulting hybrid structure of the HsTPPII holocomplex provide new insights into the mechanism of maturation and activation. Copyright © 2012 Elsevier Ltd. All rights reserved.

NIR hyperspectral compressive imager based on a modified Fabry–Perot resonator

NASA Astrophysics Data System (ADS)

Oiknine, Yaniv; August, Isaac; Blumberg, Dan G.; Stern, Adrian

2018-04-01

The acquisition of hyperspectral (HS) image datacubes with available 2D sensor arrays involves a time consuming scanning process. In the last decade, several compressive sensing (CS) techniques were proposed to reduce the HS acquisition time. In this paper, we present a method for near-infrared (NIR) HS imaging which relies on our rapid CS resonator spectroscopy technique. Within the framework of CS, and by using a modified Fabry–Perot resonator, a sequence of spectrally modulated images is used to recover NIR HS datacubes. Owing to the innovative CS design, we demonstrate the ability to reconstruct NIR HS images with hundreds of spectral bands from an order of magnitude fewer measurements, i.e. with a compression ratio of about 10:1. This high compression ratio, together with the high optical throughput of the system, facilitates fast acquisition of large HS datacubes.

An unusual dependence of human herpesvirus-8 glycoproteins-induced cell-to-cell fusion on heparan sulfate

DOE Office of Scientific and Technical Information (OSTI.GOV)

Tiwari, Vaibhav; Department of Microbiology and Immunology, University of Illinois at Chicago, Chicago, IL 60612; Department of Basic Medical Sciences, College of Osteopathic Medicine of the Pacific and College of Optometry, Western University of Health Sciences, Pomona, CA 91766

2009-12-18

Human herpesvirus-8 (HHV-8) is known to interact with cell surface heparan sulfate (HS) for entry into a target cell. Here we investigated the role of HS during HHV-8 glycoproteins-induced cell fusion. Interestingly, the observed fusion demonstrated an unusual dependence on HS as evident from following lines of evidence: (1) a significant reduction in cell-to-cell fusion occurred when target cells were treated with heparinase; (2) in a competition assay, when the effector cells expressing HHV-8 glycoproteins were challenged with soluble HS, cell-to-cell fusion was reduced; and, (3) co-expression of HHV-8 glycoproteins gH-gL on target cells resulted in inhibition of cell surfacemore » HS expression. Taken together, our results indicate that cell surface HS can play an additional role during HHV-8 pathogenesis.« less

Effect of liposome-encapsulated hemoglobin resuscitation on proteostasis in small intestinal epithelium after hemorrhagic shock

PubMed Central

Rao, Geeta; Yadav, Vivek R.; Awasthi, Shanjana; Roberts, Pamela R.

2016-01-01

Gut barrier dysfunction is the major trigger for multiorgan failure associated with hemorrhagic shock (HS). Although the molecular mediators responsible for this dysfunction are unclear, oxidative stress-induced disruption of proteostasis contributes to the gut pathology in HS. The objective of this study was to investigate whether resuscitation with nanoparticulate liposome-encapsulated hemoglobin (LEH) is able to restore the gut proteostatic mechanisms. Sprague-Dawley rats were recruited in four groups: control, HS, HS+LEH, and HS+saline. HS was induced by withdrawing 45% blood, and isovolemic LEH or saline was administered after 15 min of shock. The rats were euthanized at 6 h to collect plasma and ileum for measurement of the markers of oxidative stress, unfolded protein response (UPR), proteasome function, and autophagy. HS significantly increased the protein and lipid oxidation, trypsin-like proteasome activity, and plasma levels of IFNγ. These effects were prevented by LEH resuscitation. However, saline was not able to reduce protein oxidation and plasma IFNγ in hemorrhaged rats. Saline resuscitation also suppressed the markers of UPR and autophagy below the basal levels; the HS or LEH groups showed no effect on the UPR and autophagy. Histological analysis showed that LEH resuscitation significantly increased the villus height and thickness of the submucosal and muscularis layers compared with the HS and saline groups. Overall, the results showed that LEH resuscitation was effective in normalizing the indicators of proteostasis stress in ileal tissue. On the other hand, saline-resuscitated animals showed a decoupling of oxidative stress and cellular protective mechanisms. PMID:27288424

Parity and risk of hemorrhagic strokes.

PubMed

Jung, Sun-Young; Bae, Hee-Joon; Park, Byung-Joo; Yoon, Byung-Woo

2010-05-04

The association between parity and risk of hemorrhagic stroke (HS) remains to be clarified. This study assessed the association of parity with the overall risk of HS and compared its contribution to intracerebral hemorrhage (ICH) and subarachnoid hemorrhage (SAH). We used a database from a nationwide multicenter case-control study, in which 471 female cases with incident HS were matched at 1:2 with 942 community or hospital controls. A total of 459 HS cases and 918 controls with information on parity were included. Parity was categorized as 0-1, 2, 3, and >or=4. Adjusted odds ratios (ORs) and their 95% confidence intervals (CIs) were calculated by conditional logistic regression. As potential confounders, age, history of hypertension, history of diabetes, family history of stroke, smoking status, alcohol consumption, educational status, age at menarche, and use of oral contraceptives were included in the models. Compared with nullipara and unipara, women with parity of 2, 3, and >or=4 had significantly higher risk for total HS, ICH, and SAH, respectively. Each additional parity increased the ORs of HS (adjusted OR for total HS = 1.27 [95% CI 1.14-1.41]; adjusted OR for SAH = 1.34 [95% CI 1.13-1.58]; adjusted OR for ICH = 1.27 [95% CI 1.08-1.48]). Likelihood ratio test for trends showed a significantly increased risk with increasing parity for total HS and for both types of HS (p(trend) < 0.05 in all analyses). Increased number of childbirths may be related to an increased risk of both intracerebral hemorrhage and subarachnoid hemorrhage.

Factor h and properdin recognize different epitopes on renal tubular epithelial heparan sulfate.

PubMed

Zaferani, Azadeh; Vivès, Romain R; van der Pol, Pieter; Navis, Gerjan J; Daha, Mohamed R; van Kooten, Cees; Lortat-Jacob, Hugues; Seelen, Marc A; van den Born, Jacob

2012-09-07

During proteinuria, renal tubular epithelial cells become exposed to ultrafiltrate-derived serum proteins, including complement factors. Recently, we showed that properdin binds to tubular heparan sulfates (HS). We now document that factor H also binds to tubular HS, although to a different epitope than properdin. Factor H was present on the urinary side of renal tubular cells in proteinuric, but not in normal renal tissues and colocalized with properdin in proteinuric kidneys. Factor H dose-dependently bound to proximal tubular epithelial cells (PTEC) in vitro. Preincubation of factor H with exogenous heparin and pretreatment of PTECs with heparitinase abolished the binding to PTECs. Surface plasmon resonance experiments showed high affinity of factor H for heparin and HS (K(D) values of 32 and 93 nm, respectively). Using a library of HS-like polysaccharides, we showed that chain length and high sulfation density are the most important determinants for glycosaminoglycan-factor H interaction and clearly differ from properdin-heparinoid interaction. Coincubation of properdin and factor H did not hamper HS/heparin binding of one another, indicating recognition of different nonoverlapping epitopes on HS/heparin by factor H and properdin. Finally we showed that certain low anticoagulant heparinoids can inhibit properdin binding to tubular HS, with a minor effect on factor H binding to tubular HS. As a result, these heparinoids can control the alternative complement pathway. In conclusion, factor H and properdin interact with different HS epitopes of PTECs. These interactions can be manipulated with some low anticoagulant heparinoids, which can be important for preventing complement-derived tubular injury in proteinuric renal diseases.

Pyoverdine and proteases affect the response of Pseudomonas aeruginosa to gallium in human serum.

PubMed

Bonchi, Carlo; Frangipani, Emanuela; Imperi, Francesco; Visca, Paolo

2015-09-01

Gallium is an iron mimetic which has recently been repurposed as an antibacterial agent due to its capability to disrupt bacterial iron metabolism. In this study, the antibacterial activity of gallium nitrate [Ga(NO3)3] was investigated in complement-free human serum (HS) on 55 Pseudomonas aeruginosa clinical isolates from cystic fibrosis and non-cystic fibrosis patients. The susceptibility of P. aeruginosa to Ga(NO3)3 in HS was dependent on the bacterial ability to acquire iron from serum binding proteins (i.e., transferrin). The extent of serum protein degradation correlated well with P. aeruginosa growth in HS, while pyoverdine production did not. However, pyoverdine-deficient P. aeruginosa strains were unable to grow in HS and overcome iron restriction, albeit capable of releasing proteases. Predigestion of HS with proteinase K promoted the growth of all strains, irrespective of their ability to produce proteases and/or pyoverdine. The MICs of Ga(NO3)3 were higher in HS than in an iron-poor Casamino Acids medium, where proteolysis does not affect iron availability. Coherently, strains displaying high proteolytic activity were less susceptible to Ga(NO3)3 in HS. Our data support a model in which both pyoverdine and proteases affect the response of P. aeruginosa to Ga(NO3)3 in HS. The relatively high Ga(NO3)3 concentration required to inhibit the growth of highly proteolytic P. aeruginosa isolates in HS poses a limitation to the potential of Ga(NO3)3 in the treatment of P. aeruginosa bloodstream infections. Copyright © 2015, American Society for Microbiology. All Rights Reserved.

Pyoverdine and Proteases Affect the Response of Pseudomonas aeruginosa to Gallium in Human Serum

PubMed Central

Bonchi, Carlo; Frangipani, Emanuela; Imperi, Francesco

2015-01-01

Gallium is an iron mimetic which has recently been repurposed as an antibacterial agent due to its capability to disrupt bacterial iron metabolism. In this study, the antibacterial activity of gallium nitrate [Ga(NO3)3] was investigated in complement-free human serum (HS) on 55 Pseudomonas aeruginosa clinical isolates from cystic fibrosis and non-cystic fibrosis patients. The susceptibility of P. aeruginosa to Ga(NO3)3 in HS was dependent on the bacterial ability to acquire iron from serum binding proteins (i.e., transferrin). The extent of serum protein degradation correlated well with P. aeruginosa growth in HS, while pyoverdine production did not. However, pyoverdine-deficient P. aeruginosa strains were unable to grow in HS and overcome iron restriction, albeit capable of releasing proteases. Predigestion of HS with proteinase K promoted the growth of all strains, irrespective of their ability to produce proteases and/or pyoverdine. The MICs of Ga(NO3)3 were higher in HS than in an iron-poor Casamino Acids medium, where proteolysis does not affect iron availability. Coherently, strains displaying high proteolytic activity were less susceptible to Ga(NO3)3 in HS. Our data support a model in which both pyoverdine and proteases affect the response of P. aeruginosa to Ga(NO3)3 in HS. The relatively high Ga(NO3)3 concentration required to inhibit the growth of highly proteolytic P. aeruginosa isolates in HS poses a limitation to the potential of Ga(NO3)3 in the treatment of P. aeruginosa bloodstream infections. PMID:26149986

Diversity of the definition of stable vital sign in trauma patients: results of a nationwide survey.

PubMed

Mun, Seongpyo

2015-12-01

Hemodynamic stability (HS) based on vital sign (VS) is thought to be the most useful criteria for successful non-operative management (NOM) of blunt spleen injury (BSI). However, a consistent definition of HS has not been established. We wanted to evaluate the definition of HS through conducting a nationwide survey and find the factors affectting diversity. The questionnaire regarding the definition of HS was sent to the department of trauma surgery and emergency medicine of level I trauma center between October 2012 and November 2012. Data was compared using analysis of variance, t-test, χ2 test and logistic regression. Among five hundred and sixty-three doctors, 507 responded (90%). Forty-eight responses were incomplete, and hence, 459 (81.5%) responses were analyzed. There was a significant diversity in the definition of HS on the subject of type of blood pressure (BP), cut off value of hypotension, measuring technique of BP, duration of hypotension, whether or not using heart rate (HR) as a determinant of HS, cut off value of hypotension when the patient has comorbidity or when the patient is a pediatric patient. 91.5% replied that they were confused defining HS and felt the need to have more objective determinants. Nevertheless, 90% of the responders were not using laboratory test to define HS. Many trauma doctors are using only VS to define HS. This is why there is a confusion regarding how to define which patient is hemodynamically stable. More objective determinants such as base deficit or lactate can be useful adjuncts.

The design of a capsule polysaccharide conjugate vaccine against Campylobacter jejuni serotype HS15.

PubMed

Bertolo, Lisa; Ewing, Cheryl P; Maue, Alexander; Poly, Frederic; Guerry, Patricia; Monteiro, Mario A

2013-01-25

Campylobacter jejuni infection is now the main cause of diarrhea-related illnesses in humans. An efficacious vaccine for the traveler and developing world market would be welcomed. We are engaged in the discovery and characterization of serotype-specific C. jejuni capsule polysaccharides (CPSs) to study their role in virulence and as protective vaccine antigens. Our prototype conjugate vaccine with serotype HS23 CPS (strain 81-176) has been shown to fully protect non-human primates against diarrhea inflicted by C. jejuni HS23, but ultimately, a useful CPS-based vaccine will have to be multivalent. To this end, we describe here the creation of a CPS-conjugate vaccine against C. jejuni serotype HS15. Structural analysis revealed that a repeating block consisting of L-α-arabinofuranose (Ara) and 6-deoxy-L-α-gulo-heptopyranose (6d-gulo-Hep) comprised the CPS of serotype HS15 type strain ATCC 43442 [→3)-α-L-Araf-(1→3)-6d-L-α-gulo-Hepp(1→](n). Strategically, the non-reducing end of the CPS was activated and used in the attachment of CPS to CRM₁₉₇ to yield a conjugate vaccine. A serological assessment of the CPS(HS15)-CRM₁₉₇ conjugate with an anti-HS15 polyclonal antibody confirmed the conservation of antigenic epitopes, and subsequent inoculation of mice with CPS(HS15)-CRM₁₉₇ revealed that this conjugate was indeed capable of raising anti-CPS(HS15) antibodies. Copyright © 2012 Elsevier Ltd. All rights reserved.

[Relationship between highly sensitive cardiac troponin T and sepsis and outcome in critically ill patients].

PubMed

Wang, T T; Jiang, L

2017-10-01

Objective: To investigate the prognostic value of highly sensitive cardiac Troponin T (hs-cTn T) for sepsis in critically ill patients. Methods: Patients estimated to stay in the ICU of Fuxing Hospital for more than 24h were enrolled at from March 2014 to December 2014. Serum hs-cTn T was tested within two hours. Univariate and multivariate linear regression analyses were used to determine the association of variables with the hs-cTn T. Multivariable logistic regression analysis was used to evaluate the risk factors of 28-day mortality. Results: A total of 125 patients were finally enrolled including 68 patients with sepsis and 57 without. The levels of hs-cTn T in sepsis and non-sepsis groups were significantly different[52.0(32.5, 87.5) ng/L vs 14.0(6.5, 29.0) ng/L respectively, P <0.001]. In sepsis group, hs-cTn T among common sepsis, severe sepsis and septic shock were similar. Hs-cTn T was significantly higher in non-survivors than survivors [27(13, 52)ng/L vs 44.5(28.8, 83.5)ng/L, P <0.001]. Age, sepsis, serum creatinine were independent risk factors affecting hs-cTn T by multivariate linear regression analyses. But hs-cTn T was not a risk factor for death. Conclusion: Patients with sepsis had higher serum hs-cTn T than those without sepsis. but it was not found to be associated with the severity of sepsis.

LCR 5′ hypersensitive site specificity for globin gene activation within the active chromatin hub

PubMed Central

Peterson, Kenneth R.; Fedosyuk, Halyna; Harju-Baker, Susanna

2012-01-01

The DNaseI hypersensitive sites (HSs) of the human β-globin locus control region (LCR) may function as part of an LCR holocomplex within a larger active chromatin hub (ACH). Differential activation of the globin genes during development may be controlled in part by preferential interaction of each gene with specific individual HSs during globin gene switching, a change in conformation of the LCR holocomplex, or both. To distinguish between these possibilities, human β-globin locus yeast artificial chromosome (β-YAC) lines were produced in which the ε-globin gene was replaced with a second marked β-globin gene (βm), coupled to an intact LCR, a 5′HS3 complete deletion (5′ΔHS3) or a 5′HS3 core deletion (5′ΔHS3c). The 5′ΔHS3c mice expressed βm-globin throughout development; γ-globin was co-expressed in the embryonic yolk sac, but not in the fetal liver; and wild-type β-globin was co-expressed in adult mice. Although the 5′HS3 core was not required for βm-globin expression, previous work showed that the 5′HS3 core is necessary for ε-globin expression during embryonic erythropoiesis. A similar phenotype was observed in 5′HS complete deletion mice, except βm-globin expression was higher during primitive erythropoiesis and γ-globin expression continued into fetal definitive erythropoiesis. These data support a site specificity model of LCR HS-globin gene interaction. PMID:23042246

Thermoregulatory responses of Holstein cows exposed to experimentally induced heat stress.

PubMed

de Andrade Ferrazza, Rodrigo; Mogollón Garcia, Henry David; Vallejo Aristizábal, Viviana Helena; de Souza Nogueira, Camilla; Veríssimo, Cecília José; Sartori, José Roberto; Sartori, Roberto; Pinheiro Ferreira, João Carlos

2017-05-01

Heat stress (HS) adversely influences productivity and welfare of dairy cattle. We hypothesized that the thermoregulatory mechanisms vary depending on the exposure time to HS, with a cumulative effect on the adaptive responses and thermal strain of the cow. To identify the effect of HS on adaptive thermoregulatory mechanisms and predictors of caloric balance, Holstein cows were housed in climate chambers and randomly distributed into thermoneutral (TN; n=12) or HS (n=12) treatments for 16 days. Vaginal temperature (VT), rectal temperature (Tre), respiratory rate (RR), heart rate (HR), and dry matter intake (DMI) were measured. The temperature and humidity under TN were 25.9±0.2°C and 73.0±0.8%, respectively, and under HS were 36.3±0.3°C and 60.9±0.9%, respectively. The RR of the HS cows increased immediately after exposure to heat and was higher (76.02±1.70bpm, p<0.001) than in the TN (39.70±0.71bpm). An increase in Tre (39.87±0.07°C in the HS vs. 38.56±0.03°C in the TN, p<0.001) and in VT (39.82±0.10°C in the HS vs. 38.26±0.03°C in the TN, p<0.001) followed the increase in RR. A decrease (p<0.05) in HR occurred in the HS (62.13±0.99bpm) compared with the TN (66.23±0.79bpm); however, the magnitude of the differences was not the same over time. The DMI was lower in HS cows from the third day (8.27±0.33kgd -1 in the HS vs. 14.03±0.29kgd -1 in the TN, p<0.001), and the reduction of DMI was strongly affected (r=-0.65) by changes in the temperature humidity index. The effect of environmental variables from the previous day on physiological parameters and DMI was more important than the immediate effect, and ambient temperature represented the most determinant factor for heat exchange. The difference in the responses to acute and chronic exposure to HS suggests an adaptive response. Thus, intense thermal stress strongly influence thermoregulatory mechanisms and the acclimation process depend critically on heat exposure time. Copyright © 2017 Elsevier Ltd. All rights reserved.

Hollow sinh-Gaussian beams and their paraxial properties.

PubMed

Sun, Qiongge; Zhou, Keya; Fang, Guangyu; Zhang, Guoqiang; Liu, Zhengjun; Liu, Shutian

2012-04-23

A new mathematical model of dark-hollow beams, described as hollow sinh-Gaussian (HsG) beams, has been introduced. The intensity distributions of HsG beams are characterized by a single bright ring along the propagation whose size is determined by the order of beams; the shape of the ring can be controlled by beam width and this leads to the elliptical HsG beams. Propagation characteristics of HsG beams through an ABCD optical system have been researched, they can be regarded as superposition of a series of Hypergeometric-Gaussian (HyGG) beams. As a numerical example, the propagation characteristics of HsG beams in free space have been demonstrated graphically. © 2012 Optical Society of America

[Improvement of effectivity of photo disinfection of water from bacterial contaminants in the presence of heterogeneous sensitizers based on phthalocyanines grafted to aminopropyl silicagel].

PubMed

Maksimkina, T N; Artemova, T Z; Kuznetsova, N A; Sinitsyna, O O; Gipp, E K; Zagaĭnova, A V; Butorina, N N; Iuzhakova, O A; Krasniak, A V

2012-01-01

The possibility of using 12 heterogeneous sensitizers (HS) based on phthalocyanines covalently grafted to aminopropyl silicagel for disinfection of water from bacteria has been studied. For reliable water quality control the technique of performing bacteriological analysis in the presence of HS beads in the sample has been elaborated. The conditions increasing the efficiency of photo disinfection in the presence of HS were studied. Algorithm for estimation of photo disinfectant effect of HS against bacteria was substantiated. Obtained data confirm the perspective of further studies on the substantiation of the possibility of the application of HS for water disinfection.

Effect of human alpha 2HS glycoprotein on mouse macrophage function.

PubMed Central

Lewis, J G; André, C M

1980-01-01

alpha 2HS glycoprotein was isolated from normal adult serum. The ability of alpha 2HS glycoprotein to promote the endocytosis of radiolabelled DNA and radiolabelled latex particles by mouse macrophages was investigated. The results using both radiolabelled latex particles and radiolabelled DNA show that alpha 2HS glycoprotein enhances the ability of mouse macrophages to take up these radiolabelled substrates as compared to control cells. Images Figure 1 Figure 2 PMID:7439929

Magnolol pretreatment attenuates heat stress-induced IEC-6 cell injury.

PubMed

Mei, Chen; He, Sha-Sha; Yin, Peng; Xu, Lei; Shi, Ya-Ran; Yu, Xiao-Hong; Lyu, An; Liu, Feng-Hua; Jiang, Lin-Shu

2016-06-01

Heat stress (HS) is an important environmental stressor that adversely influences livestock during the summer. The aim of this study was to investigate whether magnolol protects against HS-induced intestinal epithelial cell injury. An intestinal epithelial cell line (IEC-6) was subjected to HS at 42 °C, with and without magnolol pretreatment. Cell injury was detected by monitoring lactate dehydrogenase (LDH) release. MTS (3-(4,5-dimethylthiazol-2-yl)-5-(3-carboxymethoxyphenyl)-2-(4-sulfophenyl)-2H-tetrazolium) assay was used to assess cell proliferation and viability, including identifying effective concentrations of magnolol. Flow cytometry confirmed G1-phase cell-cycle arrest and its alleviation by magnolol. Active DNA synthesis was measured by incorporation of nucleic acid 5-ethynyl-2'-deoxyuridine (EdU). G1-phase cell-cycle-related gene expression was assessed by real-time reverse transcription polymerase chain reaction (RT-PCR) and levels of G1-phase-related proteins by Western blotting. HS induced IEC-6 cell injury and decreased cell viability, as demonstrated by data from LDH and MTS assays, respectively. Based on a number of criteria, IEC-6 cells subjected to HS were arrested in the G1 phase of the cell cycle. Magnolol pretreatment decreased HS-induced cell injury through relief of this cell-cycle arrest. Magnolol pretreatment attenuates HS-induced injury in IEC-6 cells. Magnolol is potentially promising as a protective strategy for HS in livestock.

A pharmacological investigation of Hippophae salicifolia (HS) and Hippophae rhamnoides turkestanica (HRT) against multiple stress (C-H-R): an experimental study using rat model.

PubMed

Rathor, Richa; Sharma, Priyanka; Suryakumar, Geetha; Ganju, Lilly

2015-09-01

Hippophae salicifolia (HS) and Hippophae rhamnoides turkestanica (HRT) are abundantly found species of Hippophae in Himalayan region of India. As these plants thrive under extreme climatic conditions, it is suspected that these plants must have a unique adaptogenic property against high-altitude stress. To keeping these views in our mind, the present study was planned to evaluate the mechanism of action of aqueous extract of HS and aqueous extract of HRT against multiple stress [cold-hypoxia-restraint (C-H-R)] for their adaptogenic activity. The present study reported the adaptogenic activity of HS in facilitating tolerance to multiple stress, CHR in rats. Pre-treatment with aqueous extract of HS significantly attenuated reactive oxygen species (ROS) production, protein oxidation, and lipid peroxidation and also showed role in maintaining antioxidant status as similar to control rats. Since protein oxidation was decreased by pre-treatment of HS, protein homeostasis was also sustained by regulation of heat shock proteins (HSP70 and HSP60). Interestingly, heme oxygenase-1 (HO-1), Vascular Endothelial Growth Factor (VEGF), and nitric oxide (NO) level was also increased in HS pre-treated rats depicted its adaptogenic activity against multiple stress, CHR. Conclusively, aqueous extract of HS could use an adaptogen for high altitude-associated multiple stress (CHR).

Gene cloning, expression, and characterization of a new carboxylesterase from Serratia sp. SES-01: comparison with Escherichia coli BioHe enzyme.

PubMed

Kwon, Min-A; Kim, Hyun Suk; Oh, Joon Young; Song, Bong Keun; Song, Jae Kwang

2009-02-01

The carboxylesterase-encoding gene (bioHs) of a newly isolated strain, Serratia sp. SES-01, was cloned from the genomic DNA library by detecting formation of transparent halo around the colony on LB-tributyrin agar plates. The amino acid sequence of BioHs was highly similar to the members of the BioH enzyme family involved in the biotin biosynthetic pathway; it showed the highest similarity (91%) with that of Serratia proteamaculans. To compare BioHs with other BioH enzymes, the relatively well-known bioHe gene of E. coli was cloned with PCR. After we achieved high-level expression of soluble BioHs and BioHe through the exploration of different culture conditions, the purified BioHs and BioHe enzymes were characterized in terms of specificity, activity, and stability. BioHe was generally more robust to a change in temperature and pH and an addition of organic solvents than BioHs. The two enzymes exhibited a strong preference for carboxylesterase rather than for thioesterase and were optimal at relatively low temperatures (20-40 degrees ) and alkaline pHs (7.5-9.0). The results in this study strongly suggested that both the BioHs and BioHe enzymes would be potential candidates for use as a carboxylesterase in many industrial applications.

DNase I hypersensitivity and epsilon-globin transcriptional enhancement are separable in locus control region (LCR) HS1 mutant human beta-globin YAC transgenic mice.

PubMed

Shimotsuma, Motoshi; Okamura, Eiichi; Matsuzaki, Hitomi; Fukamizu, Akiyoshi; Tanimoto, Keiji

2010-05-07

Expression of the five beta-like globin genes (epsilon, Ggamma, Agamma, delta, beta) in the human beta-globin locus depends on enhancement by the locus control region, which consists of five DNase I hypersensitive sites (5'HS1 through 5'HS5). We report here a novel enhancer activity in 5'HS1 that appears to be potent in transfected K562 cells. Deletion analyses identified a core activating element that bound to GATA-1, and a two-nucleotide mutation that disrupted GATA-1 binding in vitro abrogated 5'HS1 enhancer activity in transfection experiments. To determine the in vivo role of this GATA site, we generated multiple lines of human beta-globin YAC transgenic mice bearing the same two-nucleotide mutation. In the mutant mice, epsilon-, but not gamma-globin, gene expression in primitive erythroid cells was severely attenuated, while adult beta-globin gene expression in definitive erythroid cells was unaffected. Interestingly, DNaseI hypersensitivity near the 5'HS1 mutant sequence was eliminated in definitive erythroid cells, whereas it was only mildly affected in primitive erythroid cells. We therefore conclude that, although the GATA site in 5'HS1 is critical for efficient epsilon-globin gene expression, hypersensitive site formation per se is independent of 5'HS1 function, if any, in definitive erythroid cells.

Depth measurements through controlled aberrations of projected patterns.

PubMed

Birch, Gabriel C; Tyo, J Scott; Schwiegerling, Jim

2012-03-12

Three-dimensional displays have become increasingly present in consumer markets. However, the ability to capture three-dimensional images in space confined environments and without major modifications to current cameras is uncommon. Our goal is to create a simple modification to a conventional camera that allows for three dimensional reconstruction. We require such an imaging system have imaging and illumination paths coincident. Furthermore, we require that any three-dimensional modification to a camera also permits full resolution 2D image capture.Here we present a method of extracting depth information with a single camera and aberrated projected pattern. A commercial digital camera is used in conjunction with a projector system with astigmatic focus to capture images of a scene. By using an astigmatic projected pattern we can create two different focus depths for horizontal and vertical features of a projected pattern, thereby encoding depth. By designing an aberrated projected pattern, we are able to exploit this differential focus in post-processing designed to exploit the projected pattern and optical system. We are able to correlate the distance of an object at a particular transverse position from the camera to ratios of particular wavelet coefficients.We present our information regarding construction, calibration, and images produced by this system. The nature of linking a projected pattern design and image processing algorithms will be discussed.

Quantitative analysis reveals crosstalk mechanisms of heat shock-induced attenuation of NF-κB signaling at the single cell level.

PubMed

Kardyńska, Małgorzata; Paszek, Anna; Śmieja, Jarosław; Spiller, David; Widłak, Wiesława; White, Michael R H; Paszek, Pawel; Kimmel, Marek

2018-04-01

Elevated temperature induces the heat shock (HS) response, which modulates cell proliferation, apoptosis, the immune and inflammatory responses. However, specific mechanisms linking the HS response pathways to major cellular signaling systems are not fully understood. Here we used integrated computational and experimental approaches to quantitatively analyze the crosstalk mechanisms between the HS-response and a master regulator of inflammation, cell proliferation, and apoptosis the Nuclear Factor κB (NF-κB) system. We found that populations of human osteosarcoma cells, exposed to a clinically relevant 43°C HS had an attenuated NF-κB p65 response to Tumor Necrosis Factor α (TNFα) treatment. The degree of inhibition of the NF-κB response depended on the HS exposure time. Mathematical modeling of single cells indicated that individual crosstalk mechanisms differentially encode HS-mediated NF-κB responses while being consistent with the observed population-level responses. In particular "all-or-nothing" encoding mechanisms were involved in the HS-dependent regulation of the IKK activity and IκBα phosphorylation, while others involving transport were "analogue". In order to discriminate between these mechanisms, we used live-cell imaging of nuclear translocations of the NF-κB p65 subunit. The single cell responses exhibited "all-or-nothing" encoding. While most cells did not respond to TNFα stimulation after a 60 min HS, 27% showed responses similar to those not receiving HS. We further demonstrated experimentally and theoretically that the predicted inhibition of IKK activity was consistent with the observed HS-dependent depletion of the IKKα and IKKβ subunits in whole cell lysates. However, a combination of "all-or-nothing" crosstalk mechanisms was required to completely recapitulate the single cell data. We postulate therefore that the heterogeneity of the single cell responses might be explained by the cell-intrinsic variability of HS-modulated IKK signaling. In summary, we show that high temperature modulates NF-κB responses in single cells in a complex and unintuitive manner, which needs to be considered in hyperthermia-based treatment strategies.

A Chimeric HS4-SAR Insulator (IS2) That Prevents Silencing and Enhances Expression of Lentiviral Vectors in Pluripotent Stem Cells

PubMed Central

Gutierrez-Guerrero, Alejandra; Cobo, Marién; Muñoz, Pilar

2014-01-01

Chromatin insulators, such as the chicken β-globin locus control region hypersensitive site 4 (HS4), and scaffold/matrix attachment regions (SARs/MARs) have been incorporated separately or in combination into retroviral vectors (RVs) in order to increase transgene expression levels, avoid silencing and reduce expression variability. However, their incorporation into RVs either produces a reduction on titer and/or expression levels or do not have sufficient effect on stem cells. In order to develop an improved insulator we decided to combine SAR elements with HS4 insulators. We designed several synthetic shorter SAR elements containing 4 or 5 MAR/SARs recognition signatures (MRS) and studied their effects on a lentiviral vector (LV) expressing eGFP through the SFFV promoter (SE). A 388 bp SAR element containing 5 MRS, named SAR2, was as efficient or superior to the other SARs analyzed. SAR2 enhanced transgene expression and reduced silencing and variability on human embryonic stem cells (hESCs). We next compared the effect of different HS4-based insulators, the HS4-Core (250 bp), the HS4-Ext (400 bp) and the HS4-650 (650 bp). All HS4 elements reduced silencing and expression variability but they also had a negative effect on transgene expression levels and titer. In general, the HS4-650 element had a better overall effect. Based on these data we developed a chimeric insulator, IS2, combining the SAR2 and the HS4-650. When incorporated into the 3′ LTR of the SE LV, the IS2 element was able to enhance expression, avoid silencing and reduce variability of expression on hESCs. Importantly, these effects were maintained after differentiation of the transduced hESCs toward the hematopoietic linage. Neither the HS4-650 nor the SAR2 elements had these effects. The IS2 element is therefore a novel insulator that confers expression stability and enhances expression of LVs on stem cells. PMID:24400083

Heat Shock Enhances the Expression of the Human T Cell Leukemia Virus Type-I (HTLV-I) Trans-Activator (Tax) Antigen in Human HTLV-I Infected Primary and Cultured T Cells.

PubMed

Kunihiro, Marie; Fujii, Hideki; Miyagi, Takuya; Takahashi, Yoshiaki; Tanaka, Reiko; Fukushima, Takuya; Ansari, Aftab A; Tanaka, Yuetsu

2016-07-11

The environmental factors that lead to the reactivation of human T cell leukemia virus type-1 (HTLV-I) in latently infected T cells in vivo remain unknown. It has been previously shown that heat shock (HS) is a potent inducer of HTLV-I viral protein expression in long-term cultured cell lines. However, the precise HTLV-I protein(s) and mechanisms by which HS induces its effect remain ill-defined. We initiated these studies by first monitoring the levels of the trans-activator (Tax) protein induced by exposure of the HTLV-I infected cell line to HS. HS treatment at 43 °C for 30 min for 24 h led to marked increases in the level of Tax antigen expression in all HTLV-I-infected T cell lines tested including a number of HTLV-I-naturally infected T cell lines. HS also increased the expression of functional HTLV-I envelope gp46 antigen, as shown by increased syncytium formation activity. Interestingly, the enhancing effect of HS was partially inhibited by the addition of the heat shock protein 70 (HSP70)-inhibitor pifithlin-μ (PFT). In contrast, the HSP 70-inducer zerumbone (ZER) enhanced Tax expression in the absence of HS. These data suggest that HSP 70 is at least partially involved in HS-mediated stimulation of Tax expression. As expected, HS resulted in enhanced expression of the Tax-inducible host antigens, such as CD83 and OX40. Finally, we confirmed that HS enhanced the levels of Tax and gp46 antigen expression in primary human CD4⁺ T cells isolated from HTLV-I-infected humanized NOD/SCID/γc null (NOG) mice and HTLV-I carriers. In summary, the data presented herein indicate that HS is one of the environmental factors involved in the reactivation of HTLV-I in vivo via enhanced Tax expression, which may favor HTLV-I expansion in vivo.

Preprocedural High-Sensitivity Cardiac Troponin T and Clinical Outcomes in Patients With Stable Coronary Artery Disease Undergoing Elective Percutaneous Coronary Intervention.

PubMed

Zanchin, Thomas; Räber, Lorenz; Koskinas, Konstantinos C; Piccolo, Raffaele; Jüni, Peter; Pilgrim, Thomas; Stortecky, Stefan; Khattab, Ahmed A; Wenaweser, Peter; Bloechlinger, Stefan; Moschovitis, Aris; Frenk, Andre; Moro, Christina; Meier, Bernhard; Fiedler, Georg M; Heg, Dik; Windecker, Stephan

2016-06-01

Cardiac troponin detected by new-generation, highly sensitive assays predicts clinical outcomes among patients with stable coronary artery disease (SCAD) treated medically. The prognostic value of baseline high-sensitivity cardiac troponin T (hs-cTnT) elevation in SCAD patients undergoing elective percutaneous coronary interventions is not well established. This study assessed the association of preprocedural levels of hs-cTnT with 1-year clinical outcomes among SCAD patients undergoing percutaneous coronary intervention. Between 2010 and 2014, 6974 consecutive patients were prospectively enrolled in the Bern Percutaneous Coronary Interventions Registry. Among patients with SCAD (n=2029), 527 (26%) had elevated preprocedural hs-cTnT above the upper reference limit of 14 ng/L. The primary end point, mortality within 1 year, occurred in 20 patients (1.4%) with normal hs-cTnT versus 39 patients (7.7%) with elevated baseline hs-cTnT (P<0.001). Patients with elevated hs-cTnT had increased risks of all-cause (hazard ratio 5.73; 95% confidence intervals 3.34-9.83; P<0.001) and cardiac mortality (hazard ratio 4.68; 95% confidence interval 2.12-10.31; P<0.001). Preprocedural hs-TnT elevation remained an independent predictor of 1-year mortality after adjustment for relevant risk factors, including age, sex, and renal failure (adjusted hazard ratio 2.08; 95% confidence interval 1.10-3.92; P=0.024). A graded mortality risk was observed across higher tertiles of elevated preprocedural hs-cTnT, but not among patients with hs-cTnT below the upper reference limit. Preprocedural elevation of hs-cTnT is observed in one fourth of SCAD patients undergoing elective percutaneous coronary intervention. Increased levels of preprocedural hs-cTnT are proportionally related to the risk of death and emerged as independent predictors of all-cause mortality within 1 year. URL: http://www.clinicaltrials.gov. Unique identifier: NCT02241291. © 2016 American Heart Association, Inc.

Short-term sandbar variability based on video imagery: Comparison between Time-Average and Time-Variance techniques

USGS Publications Warehouse

Guedes, R.M.C.; Calliari, L.J.; Holland, K.T.; Plant, N.G.; Pereira, P.S.; Alves, F.N.A.

2011-01-01

Time-exposure intensity (averaged) images are commonly used to locate the nearshore sandbar position (xb), based on the cross-shore locations of maximum pixel intensity (xi) of the bright bands in the images. It is not known, however, how the breaking patterns seen in Variance images (i.e. those created through standard deviation of pixel intensity over time) are related to the sandbar locations. We investigated the suitability of both Time-exposure and Variance images for sandbar detection within a multiple bar system on the southern coast of Brazil, and verified the relation between wave breaking patterns, observed as bands of high intensity in these images and cross-shore profiles of modeled wave energy dissipation (xD). Not only is Time-exposure maximum pixel intensity location (xi-Ti) well related to xb, but also to the maximum pixel intensity location of Variance images (xi-Va), although the latter was typically located 15m offshore of the former. In addition, xi-Va was observed to be better associated with xD even though xi-Ti is commonly assumed as maximum wave energy dissipation. Significant wave height (Hs) and water level (??) were observed to affect the two types of images in a similar way, with an increase in both Hs and ?? resulting in xi shifting offshore. This ??-induced xi variability has an opposite behavior to what is described in the literature, and is likely an indirect effect of higher waves breaking farther offshore during periods of storm surges. Multiple regression models performed on xi, Hs and ?? allowed the reduction of the residual errors between xb and xi, yielding accurate estimates with most residuals less than 10m. Additionally, it was found that the sandbar position was best estimated using xi-Ti (xi-Va) when xb was located shoreward (seaward) of its mean position, for both the first and the second bar. Although it is unknown whether this is an indirect hydrodynamic effect or is indeed related to the morphology, we found that this behavior can be explored to optimize sandbar estimation using video imagery, even in the absence of hydrodynamic data. ?? 2011 Elsevier B.V..

Highway proximity associated with cardiovascular disease risk: the influence of individual-level confounders and exposure misclassification

PubMed Central

2013-01-01

Background Elevated cardiovascular disease risk has been reported with proximity to highways or busy roadways, but proximity measures can be challenging to interpret given potential confounders and exposure error. Methods We conducted a cross sectional analysis of plasma levels of C-Reactive Protein (hsCRP), Interleukin-6 (IL-6), Tumor Necrosis Factor alpha receptor II (TNF-RII) and fibrinogen with distance of residence to a highway in and around Boston, Massachusetts. Distance was assigned using ortho-photo corrected parcel matching, as well as less precise approaches such as simple parcel matching and geocoding addresses to street networks. We used a combined random and convenience sample of 260 adults >40 years old. We screened a large number of individual-level variables including some infrequently collected for assessment of highway proximity, and included a subset in our final regression models. We monitored ultrafine particle (UFP) levels in the study areas to help interpret proximity measures. Results Using the orthophoto corrected geocoding, in a fully adjusted model, hsCRP and IL-6 differed by distance category relative to urban background: 43% (-16%,141%) and 49% (6%,110%) increase for 0-50 m; 7% (-39%,45%) and 41% (6%,86%) for 50-150 m; 54% (-2%,142%) and 18% (-11%,57%) for 150-250 m, and 49% (-4%, 131%) and 42% (6%, 89%) for 250-450 m. There was little evidence for association for TNF-RII or fibrinogen. Ortho-photo corrected geocoding resulted in stronger associations than traditional methods which introduced differential misclassification. Restricted analysis found the effect of proximity on biomarkers was mostly downwind from the highway or upwind where there was considerable local street traffic, consistent with patterns of monitored UFP levels. Conclusion We found associations between highway proximity and both hsCRP and IL-6, with non-monotonic patterns explained partly by individual-level factors and differences between proximity and UFP concentrations. Our analyses emphasize the importance of controlling for the risk of differential exposure misclassification from geocoding error. PMID:24090339

Highway proximity associated with cardiovascular disease risk: the influence of individual-level confounders and exposure misclassification.

PubMed

Brugge, Doug; Lane, Kevin; Padró-Martínez, Luz T; Stewart, Andrea; Hoesterey, Kyle; Weiss, David; Wang, Ding Ding; Levy, Jonathan I; Patton, Allison P; Zamore, Wig; Mwamburi, Mkaya

2013-10-03

Elevated cardiovascular disease risk has been reported with proximity to highways or busy roadways, but proximity measures can be challenging to interpret given potential confounders and exposure error. We conducted a cross sectional analysis of plasma levels of C-Reactive Protein (hsCRP), Interleukin-6 (IL-6), Tumor Necrosis Factor alpha receptor II (TNF-RII) and fibrinogen with distance of residence to a highway in and around Boston, Massachusetts. Distance was assigned using ortho-photo corrected parcel matching, as well as less precise approaches such as simple parcel matching and geocoding addresses to street networks. We used a combined random and convenience sample of 260 adults >40 years old. We screened a large number of individual-level variables including some infrequently collected for assessment of highway proximity, and included a subset in our final regression models. We monitored ultrafine particle (UFP) levels in the study areas to help interpret proximity measures. Using the orthophoto corrected geocoding, in a fully adjusted model, hsCRP and IL-6 differed by distance category relative to urban background: 43% (-16%,141%) and 49% (6%,110%) increase for 0-50 m; 7% (-39%,45%) and 41% (6%,86%) for 50-150 m; 54% (-2%,142%) and 18% (-11%,57%) for 150-250 m, and 49% (-4%, 131%) and 42% (6%, 89%) for 250-450 m. There was little evidence for association for TNF-RII or fibrinogen. Ortho-photo corrected geocoding resulted in stronger associations than traditional methods which introduced differential misclassification. Restricted analysis found the effect of proximity on biomarkers was mostly downwind from the highway or upwind where there was considerable local street traffic, consistent with patterns of monitored UFP levels. We found associations between highway proximity and both hsCRP and IL-6, with non-monotonic patterns explained partly by individual-level factors and differences between proximity and UFP concentrations. Our analyses emphasize the importance of controlling for the risk of differential exposure misclassification from geocoding error.

ARC-2010-ACD10-0052-206

NASA Image and Video Library

2010-03-20

For Inspiration and Recognition of Science and Technology; FIRST Robotics Competition 2010 Silicon Valley Regional held at San Jose State University, San Jose, CaliforniaThe Wild Hats of Woodside H.S. & Carlmont H. S. & Sequoia H.S & Sequoia H.S. District, CA