[Early mobilization. Competencies, responsibilities, milestones].

PubMed

Nydahl, P; Dewes, M; Dubb, R; Filipovic, S; Hermes, C; Jüttner, F; Kaltwasser, A; Klarmann, S; Klas, K; Mende, H; Rothaug, O; Schuchhardt, D

2016-03-01

Early mobilization is an evident, interprofessional concept to improve the outcome of intensive care patients. It reduces psychocognitive deficits and delirium and attenuates a general deconditioning, including atrophy of the respiratory pump and skeletal muscles. In this regard the interdisciplinary approach of early mobilization, taking into account different levels of mobilization, appears to be beneficial. The purpose of this study was to explore opinions on collaboration and tasks between different professional groups. During the 25th Bremen Conference on Intensive Medicine and Nursing on 20 February 2015, a questionnaire survey was carried out among the 120 participants of the German Early Mobilization Network meeting. In all, 102 questionnaires were analyzed. Most participants reported on the interdisciplinarity of the approach, but none of the tasks and responsibilities concerning early mobilization can be assigned to a single professional group. The practical implementation of mobilizing orally intubated patients may require two registered nurses as well as a physical therapist. Implementation in daily practice seems to be heterogeneous. There is no consensus regarding collaboration, competencies, and responsibilities with respect to early mobilization of intensive care patients. The approach to date has been characterized by a lack of interprofessional communication, which may lead to an inefficient use of the broad and varied base of knowledge and experienceof the different professions.

[Molecular mechanisms and relationship of M2-polarized macrophages with early response in multiple myeloma].

PubMed

Chen, X Y; Sun, R X; Zhang, W Y; Liu, T; Zheng, Y H; Wu, Y

2017-06-14

Objective: To investigate the relationship between M2-polarized macrophages and early response in multiple myeloma and its molecular mechanism. Methods: Two hundred and forty bone marrow biopsy tissue were collected and M2-polarized macrophages were stained by anti-CD163 monoclonal antibody. In vitro M2-polarized macrophages were derived from human peripheral blood mononuclear cell or THP-1 cells and identified by flow cytometry. Two myeloma cell lines RPMI 8226 and U266 were co-cultured with M2 macrophages using a transwell system. We measured myeloma cells proliferation through CCK-8 method and the pro-inflammatory cytokines expression (TNF-α and IL-6) by ELISA. Real time PCR was applied to measure chemokines (CCL2 and CCL3) , chemokine receptors (CCR2, CCR5) , VEGF and their receptors. In addition, flow cytometry was used to analyze the apoptosis of myeloma cells induced by dexamethasone. Results: ①Patients with high percentage of M2 macrophage involvement in bone marrow showed poorer response (23.9% versus 73.0%, χ (2)=60.31, P <0.001). ② In vitro the proliferation of RPMI 8226 cells ( P =0.005 at 24 h, P =0.020 at 36 h) or U266 myeloma cells ( P = 0.030 at 24h, P =0.020 at 36h) co-cultured with M2-polarized macrophages was higher than control group. ③In vitro the apoptotic rate of RPMI 8226 cells (29.0% versus 71.0%, t =4.97, P =0.008) or U266 myeloma cells (24.9% versus 67.7%, t =6.99, P =0.002) co-cultured with M2-polarized macrophages was lower than control group. ④ In vitro M2-polarized macrophages promoted myeloma cells secreting higher level of IL-6, TNF-α and higher expression of CCL2, CCL3, CCR2, CCR5, VEGFA, VEGFR-1,-2 compared with the non-macrophage co-culture system. Conclusion: M2-polarized macrophages promote myeloma cells proliferation and inhibit apoptosis through a very complex mechanism involving pro-inflammatory cytokines IL-6 and TNF-α, chemokines and related receptors such as CCL2, CCL3, CCR2, CCR3, and VEGF as well as related

The origins of cognitive vulnerability in early childhood: mechanisms linking early attachment to later depression.

PubMed

Morley, Tara E; Moran, Greg

2011-11-01

This paper examines the theory and research linking attachment relationships to cognitive vulnerability to depression and assesses evidence that early attachment experiences contribute to the development of these cognitive processes. Most research in this area has involved adult participants using self-report measures of both attachment and depressive vulnerabilities and thus cannot convincingly speak to the existence of such a developmental pathway. Several studies, however, have followed individuals from infancy and examined the emergence of self-esteem and responses to failure throughout childhood and adolescence. These studies suggest that early experiences in non-secure attachment relationships place an individual at-risk for developing a cognitive framework that increases their vulnerability to depression following stressful life events. The paper concludes with a discussion of how future research might best explore specific mechanisms through which distinct attachment relationships may lead to divergent developmental pathways sharing the common outcome of cognitive processes that place individuals at risk for depression. Copyright © 2011 Elsevier Ltd. All rights reserved.

Mechanisms Underlying Early Medieval Droughts in Mesoamerica

NASA Astrophysics Data System (ADS)

Bhattacharya, T.; Chiang, J. C. H.

2015-12-01

Multidecadal drought during the early Medieval Climate Anomaly (MCA, 800-1200 CE) in Mesoamerica has been implicated in the demise of many pre-Columbian societies, including the Maya. The mechanisms behind these droughts, however, are poorly understood. Researchers most often interpret these records as tracking the mean position of the ITCZ, with a southward shifted ITCZ resulting in Mesoamerican drought. This is puzzling, however, because our dynamical understanding of the ITCZ and its role in interhemispheric heat transport would suggest a more northward shifted ITCZ during the MCA. Here, we evaluate two hypotheses to reconcile existing proxies and dynamics. First, we assess whether evidence for dry conditions during the MCA is robust across multiple Mesoamerican proxy records, focusing on the influence of radiometric dating uncertainty on estimates of drought timing. Second, we use control simulations of CCSM4 and HadCM3, as well as a broader synthesis of oceanic and terrestrial proxies, to explore the mechanisms responsible for long-term drought in Mesoamerica. Ultimately, we suggest that a temporary slowdown of the AMOC, either internally or externally forced, combined with local and regional land surface feedbacks can explain these droughts in Mesoamerica.

Early life vitamin D depletion alters the postnatal response to skeletal loading in growing and mature bone

PubMed Central

Buckley, Harriet; Owen, Robert; Marin, Ana Campos; Lu, Yongtau; Eyles, Darryl; Lacroix, Damien; Reilly, Gwendolen C.; Skerry, Tim M.; Bishop, Nick J.

2018-01-01

There is increasing evidence of persistent effects of early life vitamin D exposure on later skeletal health; linking low levels in early life to smaller bone size in childhood as well as increased fracture risk later in adulthood, independently of later vitamin D status. A major determinant of bone mass acquisition across all ages is mechanical loading. We tested the hypothesis in an animal model system that early life vitamin D depletion results in abrogation of the response to mechanical loading, with consequent reduction in bone size, mass and strength during both childhood and adulthood. A murine model was created in which pregnant dams were either vitamin D deficient or replete, and their offspring moved to a vitamin D replete diet at weaning. Tibias of the offspring were mechanically loaded and bone structure, extrinsic strength and growth measured both during growth and after skeletal maturity. Offspring of vitamin D deplete mice demonstrated lower bone mass in the non loaded limb and reduced bone mass accrual in response to loading in both the growing skeleton and after skeletal maturity. Early life vitamin D depletion led to reduced bone strength and altered bone biomechanical properties. These findings suggest early life vitamin D status may, in part, determine the propensity to osteoporosis and fracture that blights later life in many individuals. PMID:29370213

Proteomic identification of early salicylate- and flg22-responsive redox-sensitive proteins in Arabidopsis

PubMed Central

Liu, Pei; Zhang, Huoming; Yu, Boying; Xiong, Liming; Xia, Yiji

2015-01-01

Accumulation of reactive oxygen species (ROS) is one of the early defense responses against pathogen infection in plants. The mechanism about the initial and direct regulation of the defense signaling pathway by ROS remains elusive. Perturbation of cellular redox homeostasis by ROS is believed to alter functions of redox-sensitive proteins through their oxidative modifications. Here we report an OxiTRAQ-based proteomic study in identifying proteins whose cysteines underwent oxidative modifications in Arabidopsis cells during the early response to salicylate or flg22, two defense pathway elicitors that are known to disturb cellular redox homeostasis. Among the salicylate- and/or flg22-responsive redox-sensitive proteins are those involved in transcriptional regulation, chromatin remodeling, RNA processing, post-translational modifications, and nucleocytoplasmic shuttling. The identification of the salicylate-/flg22-responsive redox-sensitive proteins provides a foundation from which further study can be conducted toward understanding biological significance of their oxidative modifications during the plant defense response. PMID:25720653

Brain Mechanisms Involved in Early Visual Perception.

ERIC Educational Resources Information Center

Karmel, Bernard Z.

This document presents an analysis of the early attending responses and orienting reactions of infants which can be observed at birth and shortly thereafter. Focus is on one specific orienting reaction, the early direction and maintenance of one's eyes and head toward certain stimuli instead of others. The physical properties of stimuli that…

Early changes in emotional processing as a marker of clinical response to SSRI treatment in depression.

PubMed

Godlewska, B R; Browning, M; Norbury, R; Cowen, P J; Harmer, C J

2016-11-22

Antidepressant treatment reduces behavioural and neural markers of negative emotional bias early in treatment and has been proposed as a mechanism of antidepressant drug action. Here, we provide a critical test of this hypothesis by assessing whether neural markers of early emotional processing changes predict later clinical response in depression. Thirty-five unmedicated patients with major depression took the selective serotonin re-uptake inhibitor (SSRI), escitalopram (10 mg), over 6 weeks, and were classified as responders (22 patients) versus non-responders (13 patients), based on at least a 50% reduction in symptoms by the end of treatment. The neural response to fearful and happy emotional facial expressions was assessed before and after 7 days of treatment using functional magnetic resonance imaging. Changes in the neural response to these facial cues after 7 days of escitalopram were compared in patients as a function of later clinical response. A sample of healthy controls was also assessed. At baseline, depressed patients showed greater activation to fear versus happy faces than controls in the insula and dorsal anterior cingulate. Depressed patients who went on to respond to the SSRI had a greater reduction in neural activity to fearful versus happy facial expressions after just 7 days of escitalopram across a network of regions including the anterior cingulate, insula, amygdala and thalamus. Mediation analysis confirmed that the direct effect of neural change on symptom response was not mediated by initial changes in depressive symptoms. These results support the hypothesis that early changes in emotional processing with antidepressant treatment are the basis of later clinical improvement. As such, early correction of negative bias may be a key mechanism of antidepressant drug action and a potentially useful predictor of therapeutic response.

The Role of Calcium in the Response of Osteoblasts to Mechanical Stimulation

NASA Technical Reports Server (NTRS)

Duncan, R. L.; Farach-Carson, M. C.; Pavalko, F. M.

1999-01-01

A major biomedical concern in the exploration and development of space is the rapid loss of bone associated with extended periods of spaceflight. Mineral content, bone formation, matrix protein production and total body calcium are all reduced during long-term periods of weightlessness. These effects of weightlessness appears to be due to decreases in the anabolic function of osteoblasts and osteocytes rather than changes in the resorptive activity of osteoclasts. Conversely, subjecting the skeleton to exogenous mechanical loading increases matrix protein synthesis and bone formation rate, a process which also appears mediated through osteogenic cells. Osteoblasts have been shown to respond to a number of types of mechanical stimulation. However recently we have demonstrated that osteoblasts respond to fluid shear, but not physiologic levels of mechanical strain, with increases in expression of the matrix protein, osteopontin. We have also shown similar responses in other markers for the anabolic response in bone. The expression of the early response gene, c-fos, and the inducible-isoform of the prostaglandin synthetic enzyme, cyclooygenase-2 (COX-2), both increase rapidly in response to fluid shear, but not strain. How osteoblasts and osteocytes perceive mechanical stimuli and convert this stimulus into a biochemical event within the cell is still unknown. However, examination of the cellular events following mechanical stimulation indicate that two of the earliest responses are a rapid increase in intracellular calcium ([Ca(2+)](sub i)) and a reorganization of the actin cytoskeleton. The increase in [Ca(2+)](sub i) is dependent on the presence of extracellular Ca(2+), suggesting the activation of membrane Ca(2+) channel. We have previously characterized a mechanosensitive, cation-selective channel (MSCC) in osteoblast-like clonal cells, which we postulate is important in this early response to mechanical loading. Using an antisense oligodeoxynucleotide strategy

Dissociable early attentional control mechanisms underlying cognitive and affective conflicts

PubMed Central

Chen, Taolin; Kendrick, Keith M.; Feng, Chunliang; Sun, Shiyue; Yang, Xun; Wang, Xiaogang; Luo, Wenbo; Yang, Suyong; Huang, Xiaoqi; Valdés-Sosa, Pedro A.; Gong, Qiyong; Fan, Jin; Luo, Yue-Jia

2016-01-01

It has been well documented that cognitive conflict is sensitive to the relative proportion of congruent and incongruent trials. However, few studies have examined whether affective conflict processing is modulated as a function of proportion congruency (PC). To address this question we recorded event-related potentials (ERP) while subjects performed both cognitive and affective face-word Stroop tasks. By varying the proportion of congruent and incongruent trials in each block, we examined the extent to which PC impacts both cognitive and affective conflict control at different temporal stages. Results showed that in the cognitive task an anteriorly localized early N2 component occurred predominantly in the low proportion congruency context, whereas in the affective task it was found to occur in the high proportion congruency one. The N2 effects across the two tasks were localized to the dorsolateral prefrontal cortex, where responses were increased in the cognitive task but decreased in the affective one. Furthermore, high proportions of congruent items produced both larger amplitude of a posteriorly localized sustained potential component and a larger behavioral Stroop effect in cognitive and affective tasks. Our findings suggest that cognitive and affective conflicts engage early dissociable attentional control mechanisms and a later common conflict response system. PMID:27892513

Expression of glucocorticoid receptor and early growth response gene 1 during postnatal development of two inbred strains of mice exposed to early life stress.

PubMed

Navailles, Sylvia; Zimnisky, Ross; Schmauss, Claudia

2010-07-01

Early life stress can elicit profound changes in adult gene expression and behavior. One consequence of early life stress is a decreased expression of glucocorticoid receptors (GRs) in the frontal cortex and hippocampus. However, neither the time of onset nor the mechanism(s) leading to decreased GR expression during postnatal development are known. The present study used two inbred strains of mice that differ in their behavioral responsiveness to stress (Balb/c and C57Bl/6), exposed them to an established paradigm of early life stress (infant maternal separation), and measured their expression of frontal cortical and hippocampal GRs and the putative transcriptional activator of the GR gene, early growth response gene (egr)-1, at defined stages of postnatal development. In both strains, real-time RT-PCR experiments revealed that decreased expression of GR in adolescence and adulthood is, in fact, preceded by increased GR expression during early life stress exposure. Thus, the early life stress-induced disruption of the normal stress-hyporesponsive period during infancy is accompanied by increased GR expression. Moreover, chronic treatment with the antidepressant drug fluoxetine during adolescence or adulthood reversed the effect of early life stress on adult GR mRNA expression. In contrast to the strain-independent effect of early life stress on GR expression, however, changes in egr-1 expression occurred only in Balb/c mice, and unlike the biphasic developmental changes in GR mRNA expression, egr-1 mRNA was decreased throughout postnatal development. Moreover, there was no consistent overlap of anatomic regions affected by decreased GR and egr-1 protein expression. Thus, in Balb/c mice, changes in GR and egr-1 expression can independently contribute to the phenotypes resulting from early life stress exposure. These findings illustrate that the impact of early life stress on gene expression changes is modulated by the genetic background and that the persistent

Early response in cognitive-behavior therapy for syndromes of medically unexplained symptoms.

PubMed

Kleinstäuber, Maria; Lambert, Michael J; Hiller, Wolfgang

2017-05-25

-treatment and FU-5P (-.23 ≤ r ≤ .23). Due to several limitations (e.g., small sample size, lack of a control group) the results of this study have to be interpreted cautiously. Our findings show that reliable changes in regard to affective-cognitive and behavioral variables can take place very early in CBT of patients with distressing MUS. These early changes seem to be predictive of the outcome at therapy termination. Future studies are needed in order to replicate our results, and to identify mechanisms of these early response patterns in somatoform patients. ISRCTN. ISRCTN17188363 . Registered retrospectively on 29 March 2007.

Stomatal Blue Light Response Is Present in Early Vascular Plants.

PubMed

Doi, Michio; Kitagawa, Yuki; Shimazaki, Ken-ichiro

2015-10-01

Light is a major environmental factor required for stomatal opening. Blue light (BL) induces stomatal opening in higher plants as a signal under the photosynthetic active radiation. The stomatal BL response is not present in the fern species of Polypodiopsida. The acquisition of a stomatal BL response might provide competitive advantages in both the uptake of CO2 and prevention of water loss with the ability to rapidly open and close stomata. We surveyed the stomatal opening in response to strong red light (RL) and weak BL under the RL with gas exchange technique in a diverse selection of plant species from euphyllophytes, including spermatophytes and monilophytes, to lycophytes. We showed the presence of RL-induced stomatal opening in most of these species and found that the BL responses operated in all euphyllophytes except Polypodiopsida. We also confirmed that the stomatal opening in lycophytes, the early vascular plants, is driven by plasma membrane proton-translocating adenosine triphosphatase and K(+) accumulation in guard cells, which is the same mechanism operating in stomata of angiosperms. These results suggest that the early vascular plants respond to both RL and BL and actively regulate stomatal aperture. We also found three plant species that absolutely require BL for both stomatal opening and photosynthetic CO2 fixation, including a gymnosperm, C. revoluta, and the ferns Equisetum hyemale and Psilotum nudum. © 2015 American Society of Plant Biologists. All Rights Reserved.

Global gene expression analysis of early response to chemotherapy treatment in ovarian cancer spheroids.

PubMed

L'Espérance, Sylvain; Bachvarova, Magdalena; Tetu, Bernard; Mes-Masson, Anne-Marie; Bachvarov, Dimcho

2008-02-26

Chemotherapy (CT) resistance in ovarian cancer (OC) is broad and encompasses diverse unrelated drugs, suggesting more than one mechanism of resistance. To better understand the molecular mechanisms controlling the immediate response of OC cells to CT exposure, we have performed gene expression profiling in spheroid cultures derived from six OC cell lines (OVCAR3, SKOV3, TOV-112, TOV-21, OV-90 and TOV-155), following treatment with 10,0 microM cisplatin, 2,5 microM paclitaxel or 5,0 microM topotecan for 72 hours. Exposure of OC spheroids to these CT drugs resulted in differential expression of genes associated with cell growth and proliferation, cellular assembly and organization, cell death, cell cycle control and cell signaling. Genes, functionally involved in DNA repair, DNA replication and cell cycle arrest were mostly overexpressed, while genes implicated in metabolism (especially lipid metabolism), signal transduction, immune and inflammatory response, transport, transcription regulation and protein biosynthesis, were commonly suppressed following all treatments. Cisplatin and topotecan treatments triggered similar alterations in gene and pathway expression patterns, while paclitaxel action was mainly associated with induction of genes and pathways linked to cellular assembly and organization (including numerous tubulin genes), cell death and protein synthesis. The microarray data were further confirmed by pathway and network analyses. Most alterations in gene expression were directly related to mechanisms of the cytotoxics actions in OC spheroids. However, the induction of genes linked to mechanisms of DNA replication and repair in cisplatin- and topotecan-treated OC spheroids could be associated with immediate adaptive response to treatment. Similarly, overexpression of different tubulin genes upon exposure to paclitaxel could represent an early compensatory effect to this drug action. Finally, multicellular growth conditions that are known to alter gene

Sexually Dimorphic Responses to Early Adversity: Implications for Affective Problems and Autism Spectrum Disorder

PubMed Central

Davis, Elysia Poggi; Pfaff, Donald

2014-01-01

During gestation, development proceeds at a pace that is unmatched by any other stage of the lifecycle. For these reason the human fetus is particularly susceptible not only to organizing influences, but also to pathogenic disorganizing influences. Growing evidence suggests that exposure to prenatal adversity leads to neurological changes that underlie lifetime risks for mental illness. Beginning early in gestation, males and females show differential developmental trajectories and responses to stress. It is likely that sex-dependent organization of neural circuits during the fetal period influences differential vulnerability to mental health problems. We consider in this review evidence that sexually dimorphic responses to early life stress are linked to two developmental disorders: affective problems (greater female prevalence) and autism spectrum disorder (greater male prevalence). Recent prospective studies illustrating the neurodevelopmental consequences of fetal exposure to stress and stress hormones for males and females are considered here. Plausible biological mechanisms including the role of the sexually differentiated placenta are discussed. We consider in this review evidence that sexually dimorphic responses to early life stress are linked to two sets of developmental disorders: affective problems (greater female prevalence) and autism spectrum disorders (greater male prevalence). PMID:25038479

Induction of Sirt1 by Mechanical Stretch of Skeletal Muscle through the Early Response Factor EGR1 Triggers an Antioxidative Response*

PubMed Central

Pardo, Patricia S.; Mohamed, Junaith S.; Lopez, Michael A.; Boriek, Aladin M.

2011-01-01

Mechanical loading of muscles by intrinsic muscle activity or passive stretch leads to an increase in the production of reactive oxygen species (1, 2). The NAD-dependent protein deacetylase SIRT1 is involved in the protection against oxidative stress by enhancing FOXO-driven Sod2 transcription (3–5). In this report, we unravel a mechanism triggered by mechanical stretch of skeletal muscle cells that leads to an EGR1-dependent transcriptional activation of the Sirt1 gene. The resulting transient increase in SIRT1 expression generates an antioxidative response that contributes to reactive oxygen species scavenging. PMID:20971845

Early host response in the mammary gland after experimental Streptococcus uberis challenge in heifers.

PubMed

de Greeff, Astrid; Zadoks, Ruth; Ruuls, Lisette; Toussaint, Mathilda; Nguyen, Thi Kim Anh; Downing, Alison; Rebel, Johanna; Stockhofe-Zurwieden, Norbert; Smith, Hilde

2013-06-01

Streptococcus uberis is a highly prevalent causative agent of bovine mastitis, which leads to large economic losses in the dairy industry. The aim of this study was to examine the host response during acute inflammation after experimental challenge with capsulated Strep. uberis. Gene expression in response to Strep. uberis was compared between infected and control quarters in 3 animals. All quarters (n=16) were sampled at 16 different locations. Microarray data showed that 239 genes were differentially expressed between infected and control quarters. No differences in gene expression were observed between the different locations. Microarray data were confirmed for several genes using quantitative PCR analysis. Genes differentially expressed due to early Strep. uberis mastitis represented several stages of the process of infection: (1) pathogen recognition; (2) chemoattraction of neutrophils; (3) tissue repair mechanisms; and (4) bactericidal activity. Three different pathogen recognition genes were induced: ficolins, lipopolysaccharide binding protein, and toll-like receptor 2. Calgranulins were found to be the most strongly upregulated genes during early inflammation. By histology and immunohistochemistry, we demonstrated that changes in gene expression in response to Strep. uberis were induced both in infiltrating somatic milk cells and in mammary epithelial cells, demonstrating that the latter cell type plays a role in milk production as well as immune responsiveness. Given the rapid development of inflammation or mastitis after infection, early diagnosis of (Strep. uberis) mastitis is required for prevention of disease and spread of the pathogen. Insight into host responses could help to design immunomodulatory therapies to dampen inflammation after (early) diagnosis of Strep. uberis mastitis. Future research should focus on development of these early diagnostics and immunomodulatory components for mastitis treatment. Copyright © 2013 American Dairy Science

Mechanical response of biopolymer double networks

NASA Astrophysics Data System (ADS)

Carroll, Joshua; Das, Moumita

We investigate a double network model of articular cartilage (AC) and characterize its equilibrium mechanical response. AC has very few cells and the extracellular matrix mainly determines its mechanical response. This matrix can be thought of as a double polymer network made of collagen and aggrecan. The collagen fibers are stiff and resist tension and compression forces, while aggrecans are flexible and control swelling and hydration. We construct a microscopic model made of two interconnected disordered polymer networks, with fiber elasticity chosen to qualitatively mimic the experimental system. We study the collective mechanical response of this double network as a function of the concentration and stiffness of the individual components as well as the strength of the connection between them using rigidity percolation theory. Our results may provide a better understanding of mechanisms underlying the mechanical resilience of AC, and more broadly may also lead to new perspectives on the mechanical response of multicomponent soft materials. This work was partially supported by a Cottrell College Science Award.

Local mechanical stimulation induces components of the pathogen defense response in parsley

PubMed Central

Gus-Mayer, Sabine; Naton, Beatrix; Hahlbrock, Klaus; Schmelzer, Elmon

1998-01-01

Cell suspension cultures of parsley (Petroselinum crispum) have previously been used as a suitable system for studies of the nonhost resistance response to Phytophthora sojae. In this study, we replaced the penetrating fungus by local mechanical stimulation by using a needle of the same diameter as a fungal hypha, by local application of a structurally defined fungus-derived elicitor, or by a combination of the two stimuli. Similar to the fungal infection hypha, the local mechanical stimulus alone induced the translocation of cytoplasm and nucleus to the site of stimulation, the generation of intracellular reactive oxygen intermediates (ROI), and the expression of some, but not all, elicitor-responsive genes. When the elicitor was applied locally to the cell surface without mechanical stimulation, intracellular ROI also accumulated rapidly, but morphological changes were not detected. A combination of the mechanical stimulus with simultaneous application of low doses of elicitor closely simulated early reactions to fungal infection, including cytoplasmic aggregation, nuclear migration, and ROI accumulation. By contrast, cytoplasmic rearrangements were impaired at high elicitor concentrations. Neither papilla formation nor hypersensitive cell death occurred under the conditions tested. These results suggest that mechanical stimulation by the invading fungus is responsible for the observed intracellular rearrangements and may trigger some of the previously demonstrated changes in the activity of elicitor-responsive genes, whereas chemical stimulation is required for additional biochemical processes. As yet unidentified signals may be involved in papilla formation and hypersensitive cell death. PMID:9653198

Advances in the mechanisms and early warning indicators of the postoperative cognitive dysfunction after the extracorporeal circulation.

PubMed

Liu, Chao; Han, Jian-ge

2015-02-01

The high incidence of postoperative cognitive dysfunction (POCD) after extracorporeal circulation has seriously affected the prognosis and quality of life. Its mechanism may involve the inflammatory response and oxidative stress,the excessive phosphorylation of tau protein, the decreased blood volume and oxygen in the cerebral cortex. Appropriate early warning indicators of POCD after the extracorporeal circulation should be chosen to facilitate the cross validation of the results obtained different technical approaches and thus promote the early diagnosis and treatment of POCD.

Early Peritoneal Immune Response during Echinococcus granulosus Establishment Displays a Biphasic Behavior

PubMed Central

Mourglia-Ettlin, Gustavo; Marqués, Juan Martín; Chabalgoity, José Alejandro; Dematteis, Sylvia

2011-01-01

Background Cystic echinococcosis is a worldwide distributed helminth zoonosis caused by the larval stage of Echinococcus granulosus. Human secondary cystic echinococcosis is caused by dissemination of protoscoleces after accidental rupture of fertile cysts and is due to protoscoleces ability to develop into new metacestodes. In the experimental model of secondary cystic echinococcosis mice react against protoscoleces producing inefficient immune responses, allowing parasites to develop into cysts. Although the chronic phase of infection has been analyzed in depth, early immune responses at the site of infection establishment, e.g., peritoneal cavity, have not been well studied. Because during early stages of infection parasites are thought to be more susceptible to immune attack, this work focused on the study of cellular and molecular events triggered early in the peritoneal cavity of infected mice. Principal Findings Data obtained showed disparate behaviors among subpopulations within the peritoneal lymphoid compartment. Regarding B cells, there is an active molecular process of plasma cell differentiation accompanied by significant local production of specific IgM and IgG2b antibodies. In addition, peritoneal NK cells showed a rapid increase with a significant percentage of activated cells. Peritoneal T cells showed a substantial increase, with predominance in CD4+ T lymphocytes. There was also a local increase in Treg cells. Finally, cytokine response showed local biphasic kinetics: an early predominant induction of Th1-type cytokines (IFN-γ, IL-2 and IL-15), followed by a shift toward a Th2-type profile (IL-4, IL-5, IL-6, IL-10 and IL-13). Conclusions Results reported here open new ways to investigate the involvement of immune effectors players in E. granulosus establishment, and also in the sequential promotion of Th1- toward Th2-type responses in experimental secondary cystic echinococcosis. These data would be relevant for designing rational therapies

Serotonin Transporter Gene Polymorphisms and Early Parent-Infant Interactions Are Related to Adult Male Heart Rate Response to Female Crying

PubMed Central

Truzzi, Anna; Bornstein, Marc H.; Senese, Vincenzo P.; Shinohara, Kazuyuki; Setoh, Peipei; Esposito, Gianluca

2017-01-01

Adults' adaptive interactions with intimate partners enhance well-being. Here we hypothesized that adult males' physiological responses to opposite-sex conspecifics' distress result from an interaction between an environmental factor (early social interaction with caregivers) and a genetic factor (a polymorphism within the promoter region of the serotonin transporter gene, 5-HTTLPR). We assessed heart rate changes in 42 non-married male adults to distress vocalizations (female, infant, and bonobo cries). Males' early interaction with parents was assessed using the Parental Bonding Instrument. Buccal mucosa cell samples were collected to assess their 5-HTTLPR genotype. A significant interaction emerged between early experience and genetic predisposition. Males with a genetic predisposition for higher sensitivity to environmental factors showed atypical physiological responses to adult female cries according to their experienced early maternal parenting. Environmental experiences and genetic characteristics are associated with adult males' physiological responses to socially meaningfully stimuli. Understanding the mechanisms that modulate responses to opposite-sex conspecifics may improve personal well-being and social adaptiveness. PMID:28293197

Halothane reduces the early lipopolysaccharide-induced lung inflammation in mechanically ventilated rats.

PubMed

Giraud, O; Seince, P F; Rolland, C; Leçon-Malas, V; Desmonts, J M; Aubier, M; Dehoux, M

2000-12-01

Several studies suggest that anesthetics modulate the immune response. The aim of this study was to investigate the effect of halothane and thiopental on the lung inflammatory response. Rats submitted or not to intratracheal (IT) instillation of lipopolysaccharides (LPS) were anesthetized with either halothane (0. 5, 1, or 1.5%) or thiopental (60 mg. kg(-1)) and mechanically ventilated for 4 h. Control rats were treated or not by LPS without anesthesia. Lung inflammation was assessed by total and differential cell counts in bronchoalveolar lavage fluids (BALF) and by cytokine measurements (tumor necrosis factor-alpha [TNF-alpha], interleukin-6 [IL-6], macrophage inflammatory protein-2 [MIP-2], and monocyte chemoattractant protein-1 [MCP-1]) in BALF and lung homogenates. In the absence of LPS treatment, neither halothane nor thiopental modified the moderate inflammatory response induced by tracheotomy or mechanical ventilation. Cell recruitment and cytokine concentrations were increased in all groups receiving IT LPS. However, in halothane-anesthetized rats (halothane > or = 1%), but not in thiopental-anesthetized rats, the LPS-induced lung inflammation was altered in a dose-dependent manner. Indeed, when using 1% halothane, polymorphonuclear leukocyte (PMN) recruitment was decreased by 55% (p < 0.001) and TNF-alpha, IL-6, and MIP-2 concentrations in BALF and lung homogenates were decreased by more than 60% (p < 0.001) whereas total protein and MCP-1 concentrations remained unchanged. The decrease of MIP-2 (observed at the protein and messenger RNA [mRNA] level) was strongly correlated to the decrease of PMN recruitment (r = 0.73, p < 0.05). This halothane-reduced lung inflammatory response was transient and was reversed 20 h after the end of the anesthesia. Our study shows that halothane > or = 1%, delivered during 4 h by mechanical ventilation, but not mechanical ventilation per se, alters the early LPS-induced lung inflammation in the rat, suggesting a specific

Early warning systems and rapid response to the deteriorating patient in hospital: A realist evaluation.

PubMed

McGaughey, Jennifer; O'Halloran, Peter; Porter, Sam; Trinder, John; Blackwood, Bronagh

2017-12-01

To test the Rapid Response Systems programme theory against actual practice components of the Rapid Response Systems implemented to identify those contexts and mechanisms which have an impact on the successful achievement of desired outcomes in practice. Rapid Response Systems allow deteriorating patients to be recognized using Early Warning Systems, referred early via escalation protocols and managed at the bedside by competent staff. Realist evaluation. The research design was an embedded multiple case study approach of four wards in two hospitals in Northern Ireland which followed the principles of Realist Evaluation. We used various mixed methods including individual and focus group interviews, observation of nursing practice between June-November 2010 and document analysis of Early Warning Systems audit data between May-October 2010 and hospital acute care training records over 4.5 years from 2003-2008. Data were analysed using NiVivo8 and SPPS. A cross-case analysis highlighted similar patterns of factors which enabled or constrained successful recognition, referral and response to deteriorating patients in practice. Key enabling factors were the use of clinical judgement by experienced nurses and the empowerment of nurses as a result of organizational change associated with implementation of Early Warning System protocols. Key constraining factors were low staffing and inappropriate skill mix levels, rigid implementation of protocols and culturally embedded suboptimal communication processes. Successful implementation of Rapid Response Systems was dependent on adopting organizational and cultural changes that facilitated staff empowerment, flexible implementation of protocols and ongoing experiential learning. © 2017 John Wiley & Sons Ltd.

Modeling the mechanical response of PBX 9501

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

Ragaswamy, Partha; Lewis, Matthew W; Liu, Cheng

2010-01-01

An engineering overview of the mechanical response of Plastic-Bonded eXplosives (PBXs), specifically PBX 9501, will be provided with emphasis on observed mechanisms associated with different types of mechanical testing. Mechanical tests in the form of uniaxial tension, compression, cyclic loading, creep (compression and tension), and Hopkinson bar show strain rate and temperature dependence. A range of mechanical behavior is observed which includes small strain recoverable response in the form of viscoelasticity; change in stiffness and softening beyond peak strength due to damage in the form microcracks, debonding, void formation and the growth of existing voids; inelastic response in the formmore » of irrecoverable strain as shown in cyclic tests, and viscoelastic creep combined with plastic response as demonstrated in creep and recovery tests. The main focus of this paper is to elucidate the challenges and issues involved in modeling the mechanical behavior of PBXs for simulating thermo-mechanical responses in engineering components. Examples of validation of a constitutive material model based on a few of the observed mechanisms will be demonstrated against three point bending, split Hopkinson pressure bar and Brazilian disk geometry.« less

Quantitative Proteomic Profiling of Early and Late Responses to Salicylic Acid in Cucumber Leaves

PubMed Central

Li, Liang; Shang, Qing-Mao

2016-01-01

Salicylic acid (SA) is an important phytohormone that plays vital regulatory roles in plant growth, development, and stress responses. However, studies on the molecular mechanism of SA, especially during the early SA responses, are lagging behind. In this study, we initiated a comprehensive isobaric tag for relative and absolute quantitation (iTRAQ)-based proteomic analysis to explore the early and late SA-responsive proteins in leaves of cucumber (Cucumis sativus L.) seedlings. Upon SA application through the roots, endogenous SA accumulated in cucumber leaves. By assaying the changes in marker gene expression and photosynthetic rate, we collected samples at 12 h and 72 h post treatment (hpt) to profile the early and late SA responsiveness, respectively. The iTRAQ assay followed by tandem mass spectrometry revealed 135 differentially expressed proteins (DEPs) at 12 hpt and 301 DEPs at 72 hpt. The functional categories for these SA-responsive proteins included in a variety of biochemical processes, including photosynthesis, redox homeostasis, carbohydrate and energy metabolism, lipid metabolism, transport, protein folding and modification, proteolysis, cell wall organization, and the secondary phenylpropanoid pathway. Conclusively, based on the abundant changes of these DEPs, together with their putative functions, we proposed a possible SA-responsive protein network. It appears that SA could elicit reactive oxygen species (ROS) production via enhancing the photosynthetic electron transferring, and then confer some growth-promoting and stress-priming effects on cells during the late phase, including enhanced photosynthesis and ROS scavenging, altered carbon metabolic flux for the biosynthesis of amino acids and nucleotides, and cell wall reorganization. Overall, the present iTRAQ assay provides higher proteome coverage and deepened our understanding of the molecular basis of SA-responses. PMID:27551830

Plant Responses to Brief Touching: A Mechanism for Early Neighbour Detection?

PubMed

Markovic, Dimitrije; Nikolic, Neda; Glinwood, Robert; Seisenbaeva, Gulaim; Ninkovic, Velemir

2016-01-01

In natural habitats plants can be exposed to brief and light contact with neighbouring plants. This mechanical stimulus may represent a cue that induces responses to nearby plants. However, little is known about the effect of touching on plant growth and interaction with insect herbivores. To simulate contact between plants, a soft brush was used to apply light and brief mechanical stimuli to terminal leaves of potato Solanum tuberosum L. The number of non-glandular trichomes on the leaf surface was counted on images made by light microscope while glandular trichomes and pavement cells were counted on images made under scanning electronic microscope. Volatile compounds were identified and quantified using coupled gas chromatography-mass spectrometry (GC-MS). Treated plants changed their pattern of biomass distribution; they had lower stem mass fraction and higher branch and leaf mass fraction than untouched plants. Size, weight and number of tubers were not significantly affected. Touching did not cause trichome damage nor change their total number on touched terminal leaves. However, on primary leaves the number of glandular trichomes and pavement cells was significantly increased. Touching altered the volatile emission of treated plants; they released higher quantities of the sesquiterpenes (E)-β-caryophyllene, germacrene D-4-ol and (E)-nerolidol, and lower quantities of the terpenes (E)-ocimene and linalool, indicating a systemic effect of the treatment. The odour of touched plants was significantly less preferred by the aphids Macrosiphum euphorbiae and Myzus persicae compared to odour of untouched plants. The results suggest that light contact may have a potential role in the detection of neighbouring plants and may affect plant-insect interactions.

Plant Responses to Brief Touching: A Mechanism for Early Neighbour Detection?

PubMed Central

Markovic, Dimitrije; Nikolic, Neda; Glinwood, Robert; Seisenbaeva, Gulaim; Ninkovic, Velemir

2016-01-01

In natural habitats plants can be exposed to brief and light contact with neighbouring plants. This mechanical stimulus may represent a cue that induces responses to nearby plants. However, little is known about the effect of touching on plant growth and interaction with insect herbivores. To simulate contact between plants, a soft brush was used to apply light and brief mechanical stimuli to terminal leaves of potato Solanum tuberosum L. The number of non-glandular trichomes on the leaf surface was counted on images made by light microscope while glandular trichomes and pavement cells were counted on images made under scanning electronic microscope. Volatile compounds were identified and quantified using coupled gas chromatography–mass spectrometry (GC-MS). Treated plants changed their pattern of biomass distribution; they had lower stem mass fraction and higher branch and leaf mass fraction than untouched plants. Size, weight and number of tubers were not significantly affected. Touching did not cause trichome damage nor change their total number on touched terminal leaves. However, on primary leaves the number of glandular trichomes and pavement cells was significantly increased. Touching altered the volatile emission of treated plants; they released higher quantities of the sesquiterpenes (E)-β-caryophyllene, germacrene D-4-ol and (E)-nerolidol, and lower quantities of the terpenes (E)-ocimene and linalool, indicating a systemic effect of the treatment. The odour of touched plants was significantly less preferred by the aphids Macrosiphum euphorbiae and Myzus persicae compared to odour of untouched plants. The results suggest that light contact may have a potential role in the detection of neighbouring plants and may affect plant-insect interactions. PMID:27828995

Modeling the Regulatory Mechanisms by Which NLRX1 Modulates Innate Immune Responses to Helicobacter pylori Infection

PubMed Central

Philipson, Casandra W.; Bassaganya-Riera, Josep; Viladomiu, Monica; Kronsteiner, Barbara; Abedi, Vida; Hoops, Stefan; Michalak, Pawel; Kang, Lin; Girardin, Stephen E.; Hontecillas, Raquel

2015-01-01

Helicobacter pylori colonizes half of the world’s population as the dominant member of the gastric microbiota resulting in a lifelong chronic infection. Host responses toward the bacterium can result in asymptomatic, pathogenic or even favorable health outcomes; however, mechanisms underlying the dual role of H. pylori as a commensal versus pathogenic organism are not well characterized. Recent evidence suggests mononuclear phagocytes are largely involved in shaping dominant immunity during infection mediating the balance between host tolerance and succumbing to overt disease. We combined computational modeling, bioinformatics and experimental validation in order to investigate interactions between macrophages and intracellular H. pylori. Global transcriptomic analysis on bone marrow-derived macrophages (BMDM) in a gentamycin protection assay at six time points unveiled the presence of three sequential host response waves: an early transient regulatory gene module followed by sustained and late effector responses. Kinetic behaviors of pattern recognition receptors (PRRs) are linked to differential expression of spatiotemporal response waves and function to induce effector immunity through extracellular and intracellular detection of H. pylori. We report that bacterial interaction with the host intracellular environment caused significant suppression of regulatory NLRC3 and NLRX1 in a pattern inverse to early regulatory responses. To further delineate complex immune responses and pathway crosstalk between effector and regulatory PRRs, we built a computational model calibrated using time-series RNAseq data. Our validated computational hypotheses are that: 1) NLRX1 expression regulates bacterial burden in macrophages; and 2) early host response cytokines down-regulate NLRX1 expression through a negative feedback circuit. This paper applies modeling approaches to characterize the regulatory role of NLRX1 in mechanisms of host tolerance employed by macrophages to

(−)-Epigallocatechin Gallate Targets Notch to Attenuate the Inflammatory Response in the Immediate Early Stage in Human Macrophages

PubMed Central

Wang, Tengfei; Xiang, Zemin; Wang, Ya; Li, Xi; Fang, Chongye; Song, Shuang; Li, Chunlei; Yu, Haishuang; Wang, Han; Yan, Liang; Hao, Shumei; Wang, Xuanjun; Sheng, Jun

2017-01-01

Inflammation plays important roles at different stages of diabetes mellitus, tumorigenesis, and cardiovascular diseases. (−)-Epigallocatechin gallate (EGCG) can attenuate inflammatory responses effectively. However, the immediate early mechanism of EGCG in inflammation remains unclear. Here, we showed that EGCG attenuated the inflammatory response in the immediate early stage of EGCG treatment by shutting off Notch signaling and that the effect did not involve the 67-kDa laminin receptor, the common receptor for EGCG. EGCG eliminated mature Notch from the cell membrane and the nuclear Notch intercellular domain, the active form of Notch, within 2 min by rapid degradation via the proteasome pathway. Transcription of the Notch target gene was downregulated simultaneously. Knockdown of Notch 1/2 expression by RNA interference impaired the downregulation of the inflammatory response elicited by EGCG. Further study showed that EGCG inhibited lipopolysaccharide-induced inflammation and turned off Notch signaling in human primary macrophages. Taken together, our results show that EGCG targets Notch to regulate the inflammatory response in the immediate early stage. PMID:28443100

Early developmental gene regulation in Strongylocentrotus purpuratus embryos in response to elevated CO₂ seawater conditions.

PubMed

Hammond, LaTisha M; Hofmann, Gretchen E

2012-07-15

Ocean acidification, or the increased uptake of CO(2) by the ocean due to elevated atmospheric CO(2) concentrations, may variably impact marine early life history stages, as they may be especially susceptible to changes in ocean chemistry. Investigating the regulatory mechanisms of early development in an environmental context, or ecological development, will contribute to increased understanding of potential organismal responses to such rapid, large-scale environmental changes. We examined transcript-level responses to elevated seawater CO(2) during gastrulation and the initiation of spiculogenesis, two crucial developmental processes in the purple sea urchin, Strongylocentrotus purpuratus. Embryos were reared at the current, accepted oceanic CO(2) concentration of 380 microatmospheres (μatm), and at the elevated levels of 1000 and 1350 μatm, simulating predictions for oceans and upwelling regions, respectively. The seven genes of interest comprised a subset of pathways in the primary mesenchyme cell gene regulatory network (PMC GRN) shown to be necessary for the regulation and execution of gastrulation and spiculogenesis. Of the seven genes, qPCR analysis indicated that elevated CO(2) concentrations only had a significant but subtle effect on two genes, one important for early embryo patterning, Wnt8, and the other an integral component in spiculogenesis and biomineralization, SM30b. Protein levels of another spicule matrix component, SM50, demonstrated significant variable responses to elevated CO(2). These data link the regulation of crucial early developmental processes with the environment that these embryos would be developing within, situating the study of organismal responses to ocean acidification in a developmental context.

Early change in coping strategies in responsive treatments for borderline personality disorder: A mediation analysis.

PubMed

Kramer, Ueli; Keller, Sabine; Caspar, Franz; de Roten, Yves; Despland, Jean-Nicolas; Kolly, Stéphane

2017-05-01

Difficulty in emotion regulation is a hallmark feature of patients with borderline personality disorder (BPD). Therefore, change in the frequency of certain patients' coping strategies-aiming at emotion regulation-are among the most promising mechanisms of change in treatments for BPD. In parallel, it was highlighted that therapist responsiveness significantly contributed to outcome across treatment approaches (Stiles, 2009). Based on a randomized controlled trial (Kramer et al., 2014), the present process-outcome mediation analysis aims at examining the patient's early change in frequency of coping strategies-in particular the decrease in behavioral forms of coping-as potential mechanism of change in responsive treatments for BPD. A total of 57 patients with BPD were included in the present analysis, out of whom 27 were randomly assigned to a 10-session psychiatric treatment and 30 to a 10-session psychiatric treatment augmented with the responsive intervention of the motive-oriented therapeutic relationship (Caspar, 2007). The 1st, 5th, and 9th session of each therapy were transcribed and analyzed using the Coping Action Pattern Rating Scale (Perry et al., 2005; 171 sessions analyzed in total), a validated observer-rated method for assessing coping strategies in the therapy process. Psychological distress was assessed using the OQ-45 at intake, after Session 5, and after Session 10. The results confirmed a responsiveness effect associated with the motive-oriented therapeutic relationship and showed a significant decrease in frequency of behavioral forms of coping, F(1, 54) = 3.09, p = .05, d = .56, which was not different between the 2 conditions. In addition, we demonstrated that the early decrease in behavioral forms of coping between Sessions 1 and 5 partially mediated the link between the group assignment and the change in psychological distress between Sessions 5 and 10. These results shed light on the centrality of therapist responsiveness in treatments for

21 CFR 882.1880 - Evoked response mechanical stimulator.

Code of Federal Regulations, 2010 CFR

2010-04-01

... 21 Food and Drugs 8 2010-04-01 2010-04-01 false Evoked response mechanical stimulator. 882.1880... mechanical stimulator. (a) Identification. An evoked response mechanical stimulator is a device used to produce a mechanical stimulus or a series of mechanical stimuli for the purpose of measuring a patient's...

Blood gene expression profiling of an early acetaminophen response.

PubMed

Bushel, P R; Fannin, R D; Gerrish, K; Watkins, P B; Paules, R S

2017-06-01

Acetaminophen can adversely affect the liver especially when overdosed. We used whole blood as a surrogate to identify genes as potential early indicators of an acetaminophen-induced response. In a clinical study, healthy human subjects were dosed daily with 4 g of either acetaminophen or placebo pills for 7 days and evaluated over the course of 14 days. Alanine aminotransferase (ALT) levels for responders to acetaminophen increased between days 4 and 9 after dosing, and 12 genes were detected with expression profiles significantly altered within 24 h. The early responsive genes separated the subjects by class and dose period. In addition, the genes clustered patients who overdosed on acetaminophen apart from controls and also predicted the exposure classifications with 100% accuracy. The responsive genes serve as early indicators of an acetaminophen exposure, and their gene expression profiles can potentially be evaluated as molecular indicators for further consideration.

Blood Gene Expression Profiling of an Early Acetaminophen Response

PubMed Central

Bushel, Pierre R.; Fannin, Rick D.; Gerrish, Kevin; Watkins, Paul B.; Paules, Richard S.

2018-01-01

Acetaminophen can adversely affect the liver especially when overdosed. We used whole blood as a surrogate to identify genes as potential early indicators of an acetaminophen-induced response. In a clinical study, healthy human subjects were dosed daily with 4g of either acetaminophen or placebo pills for 7 days and evaluated over the course of 14 days. Alanine aminotransferase (ALT) levels for responders to acetaminophen increased between days 4 and 9 after dosing and 12 genes were detected with expression profiles significantly altered within 24 hrs. The early responsive genes separated the subjects by class and dose period. In addition, the genes clustered patients who overdosed on acetaminophen apart from controls and also predicted the exposure classifications with 100% accuracy. The responsive genes serve as early indicators of an acetaminophen exposure and their gene expression profiles can potentially be evaluated as molecular indicators for further consideration. PMID:26927286

Early response to psychological trauma--what GPs can do.

PubMed

Wade, Darryl; Howard, Alexandra; Fletcher, Susan; Cooper, John; Forbes, David

2013-09-01

There is a high prevalence of psychological trauma exposure among primary care patients. General practitioners are well placed to provide appropriate support for patients coping with trauma. This article outlines an evidence-based early response to psychological trauma. Psychological first aid is the preferred approach in providing early assistance to patients who have experienced a traumatic event. General practitioners can be guided by five empirically derived principles in their early response: promoting a sense of safety, calming, self efficacy, connectedness and hope. Structured psychological interventions, including psychological debriefing, are not routinely recommended in the first few weeks following trauma exposure. General practitioner self care is an important aspect of providing post-trauma patient care.

Prediction in the service of comprehension: modulated early brain responses to omitted speech segments.

PubMed

Bendixen, Alexandra; Scharinger, Mathias; Strauß, Antje; Obleser, Jonas

2014-04-01

Speech signals are often compromised by disruptions originating from external (e.g., masking noise) or internal (e.g., inaccurate articulation) sources. Speech comprehension thus entails detecting and replacing missing information based on predictive and restorative neural mechanisms. The present study targets predictive mechanisms by investigating the influence of a speech segment's predictability on early, modality-specific electrophysiological responses to this segment's omission. Predictability was manipulated in simple physical terms in a single-word framework (Experiment 1) or in more complex semantic terms in a sentence framework (Experiment 2). In both experiments, final consonants of the German words Lachs ([laks], salmon) or Latz ([lats], bib) were occasionally omitted, resulting in the syllable La ([la], no semantic meaning), while brain responses were measured with multi-channel electroencephalography (EEG). In both experiments, the occasional presentation of the fragment La elicited a larger omission response when the final speech segment had been predictable. The omission response occurred ∼125-165 msec after the expected onset of the final segment and showed characteristics of the omission mismatch negativity (MMN), with generators in auditory cortical areas. Suggestive of a general auditory predictive mechanism at work, this main observation was robust against varying source of predictive information or attentional allocation, differing between the two experiments. Source localization further suggested the omission response enhancement by predictability to emerge from left superior temporal gyrus and left angular gyrus in both experiments, with additional experiment-specific contributions. These results are consistent with the existence of predictive coding mechanisms in the central auditory system, and suggestive of the general predictive properties of the auditory system to support spoken word recognition. Copyright © 2014 Elsevier Ltd. All

Using cell and organ culture models to analyze responses of bone cells to mechanical stimulation.

PubMed

Pitsillides, Andrew A; Rawlinson, Simon C F

2012-01-01

Bone cells of the osteoblastic lineage are responsive to the local mechanical environment. Through integration of a number of possible loading-induced regulatory stimuli, osteocyte, osteoblast, and osteoclast behaviour is organized to fashion a skeletal element of sufficient strength and toughness to resist fracture and crack propagation. Early pre-osteogenic responses had been determined in vivo and this led to the development of bone organ culture models to elucidate other pre-osteogenic responses where osteocytes and osteoblasts retain the natural orientation, connections and attachments to their native extracellular matrix. The application of physiological mechanical loads to bone in these organ culture models generates the regulatory stimuli. As a consequence, these experiments can be used to illustrate the distinctive mechanisms by which osteocytes and osteoblasts respond to mechanical loads and also differences in these responses, suggesting co-ordinated and cooperatively between cell populations. Organ explant cultures are awkward to maintain, and have a limited life, but length of culture times are improving. Monolayer cultures are much easier to maintain and permit the application of a particular mechanical stimulation to be studied in isolation; mainly direct mechanical strain or fluid shear strains. These allow for the response of a single cell type to the applied mechanical stimulation to be monitored precisely.The techniques that can be used to apply mechanical strain to bone and bone cells have not advanced greatly since the first edition. The output from such experiments has, however, increased substantially and their importance is now more broadly accepted. This suggests a growing use of these approaches and an increasing awareness of the importance of the mechanical environment in controlling normal bone cell behaviour. We expand the text to include additions and modifications made to the straining apparatus and update the research cited to

Health responsibility and workplace health promotion among women: early detection of cancer.

PubMed

Kushnir, T; Rabinowitz, S; Melamed, S; Weisberg, E; Ribak, J

1995-01-01

The importance of health responsibility as one aspect of a health-promoting lifestyle has been emphasized repeatedly. Yet there are only a few empirical studies of its role in preventive behavior. We examined the relationship between health responsibility and early-detection practices for breast and cervical cancer. A group of 253 women employees of a large industrial company participated in a cancer screening program subsidized by the employer. They completed questionnaires assessing health responsibility and reported early-detection practices: frequency of breast self-examination and physician breast examinations, frequency of Pap tests, and time lapsed since last Pap test and breast examinations. Health responsibility was a significant independent predictor of breast examination indicators but not of Pap tests. Education level was an important predictor for Pap tests, and age predicted most early-detection practices. The findings lend some support to the role of health responsibility in initiating breast examinations. Better prediction of early-detection practices could be achieved by adding cognitive and emotional components to the existing responsibility scale and by distinguishing between retrospective and prospective responsibility.

Presence of early stage cancer does not impair the early protein metabolic response to major surgery

PubMed Central

Klimberg, V. Suzanne; Allasia, Arianna; Deutz, Nicolaas EP

2017-01-01

Abstract Background Combined bilateral mastectomy and reconstruction is a common major surgical procedure in women with breast cancer and in those with a family history of breast cancer. As this large surgical procedure induces muscle protein loss, a preserved anabolic response to nutrition is warranted for optimal recovery. It is unclear whether the presence of early stage cancer negatively affects the protein metabolic response to major surgery as this would mandate perioperative nutritional support. Methods In nine women with early stage (Stage II) breast malignancy and nine healthy women with a genetic predisposition to breast cancer undergoing the same large surgical procedure, we examined whether surgery influences the catabolic response to overnight fasting and the anabolic response to nutrition differently. Prior to and within 24 h after combined bilateral mastectomy and reconstruction surgery, whole body protein synthesis and breakdown rates were assessed after overnight fasting and after meal intake by stable isotope methodology to enable the calculation of net protein catabolism in the post‐absorptive state and net protein anabolic response to a meal. Results Major surgery resulted in an up‐regulation of post‐absorptive protein synthesis and breakdown rates (P < 0.001) and lower net protein catabolism (P < 0.05) and was associated with insulin resistance and increased systemic inflammation (P < 0.01). Net anabolic response to the meal was reduced after surgery (P < 0.05) but higher in cancer (P < 0.05) indicative of a more preserved meal efficiency. The significant relationship between net protein anabolism and the amount of amino acids available in the circulation (R 2 = 0.85, P < 0.001) was independent of the presence of non‐cachectic early stage breast cancer or surgery. Conclusions The presence of early stage breast cancer does not enhance the normal catabolic response to major surgery or further attenuates the

Presence of early stage cancer does not impair the early protein metabolic response to major surgery.

PubMed

Engelen, Mariëlle P K J; Klimberg, V Suzanne; Allasia, Arianna; Deutz, Nicolaas Ep

2017-06-01

Combined bilateral mastectomy and reconstruction is a common major surgical procedure in women with breast cancer and in those with a family history of breast cancer. As this large surgical procedure induces muscle protein loss, a preserved anabolic response to nutrition is warranted for optimal recovery. It is unclear whether the presence of early stage cancer negatively affects the protein metabolic response to major surgery as this would mandate perioperative nutritional support. In nine women with early stage (Stage II) breast malignancy and nine healthy women with a genetic predisposition to breast cancer undergoing the same large surgical procedure, we examined whether surgery influences the catabolic response to overnight fasting and the anabolic response to nutrition differently. Prior to and within 24 h after combined bilateral mastectomy and reconstruction surgery, whole body protein synthesis and breakdown rates were assessed after overnight fasting and after meal intake by stable isotope methodology to enable the calculation of net protein catabolism in the post-absorptive state and net protein anabolic response to a meal. Major surgery resulted in an up-regulation of post-absorptive protein synthesis and breakdown rates (P < 0.001) and lower net protein catabolism (P < 0.05) and was associated with insulin resistance and increased systemic inflammation (P < 0.01). Net anabolic response to the meal was reduced after surgery (P < 0.05) but higher in cancer (P < 0.05) indicative of a more preserved meal efficiency. The significant relationship between net protein anabolism and the amount of amino acids available in the circulation (R 2  = 0.85, P < 0.001) was independent of the presence of non-cachectic early stage breast cancer or surgery. The presence of early stage breast cancer does not enhance the normal catabolic response to major surgery or further attenuates the anabolic response to meal intake within 24 h after

Temperament and Attention as Core Mechanisms in the Early Emergence of Anxiety

PubMed Central

Pérez-Edgar, Koraly; Taber-Thomas, Bradley; Auday, Eran; Morales, Santiago

2015-01-01

Anxiety is a pervasive, impairing, and early appearing form of psychopathology. Even when anxiety remits, children remain at a two- to threefold increased risk for the later emergence of a mood disorder. Therefore, it is imperative to identify and examine underlying mechanisms that may shape early emerging patterns of behavior that are associated with anxiety. One of the strongest and first visible risk factors is childhood temperament. In particular, children who are behaviorally inhibited or temperamentally shy are more likely to exhibit signs of anxiety by adolescence. However, not all shy children do so, despite the early risk. We know that attention mechanisms, particularly the presence of attention biases toward or away from threat, can play a critical role in the emergence of anxiety. The current chapter will bring together these separate lines of research to examine the ways in which attention can modulate the documented link between early temperament and later anxiety. In doing so, the chapter will highlight multiple levels of analysis that focus on the behavioral, cognitive, and neural mechanisms in the temperament-attention-anxiety network. The chapter will help identify both markers and mechanisms of risk, supporting future work aimed at improving theory and intervention by focusing on attention biases to environmental threat. PMID:26663953

Early life socioeconomic position and immune response to persistent infections among elderly Latinos.

PubMed

Meier, Helen C S; Haan, Mary N; Mendes de Leon, Carlos F; Simanek, Amanda M; Dowd, Jennifer B; Aiello, Allison E

2016-10-01

Persistent infections, such as cytomegalovirus (CMV), herpes simplex virus-1 (HSV-1), Helicobacter pylori (H. pylori), and Toxoplasma gondii (T. gondii), are common in the U.S. but their prevalence varies by socioeconomic status. It is unclear if early or later life socioeconomic position (SEP) is a more salient driver of disparities in immune control of these infections. Using data from the Sacramento Area Latino Study on Aging, we examined whether early or later life SEP was the strongest predictor of immune control later in life by contrasting two life course models, the critical period model and the chain of risk model. Early life SEP was measured as a latent variable, derived from parental education and occupation, and food availability. Indicators for SEP in later life included education level and occupation. Individuals were categorized by immune response to each pathogen (seronegative, low, medium and high) with increasing immune response representing poorer immune control. Cumulative immune response was estimated using a latent profile analysis with higher total immune response representing poorer immune control. Structural equation models were used to examine direct, indirect and total effects of early life SEP on each infection and cumulative immune response, controlling for age and gender. The direct effect of early life SEP on immune response was not statistically significant for the infections or cumulative immune response. Higher early life SEP was associated with lower immune response for T. gondii, H. pylori and cumulative immune response through pathways mediated by later life SEP. For CMV, higher early life SEP was both directly associated and partially mediated by later life SEP. No association was found between SEP and HSV-1. Findings from this study support a chain of risk model, whereby early life SEP acts through later life SEP to affect immune response to persistent infections in older age. Copyright © 2016 Elsevier Ltd. All rights

A New Experimental Polytrauma Model in Rats: Molecular Characterization of the Early Inflammatory Response

PubMed Central

Weckbach, Sebastian; Perl, Mario; Heiland, Tim; Braumüller, Sonja; Stahel, Philip F.; Flierl, Michael A.; Ignatius, Anita; Gebhard, Florian; Huber-Lang, Markus

2012-01-01

Background. The molecular mechanisms of the immune response after polytrauma are highly complex and far from fully understood. In this paper, we characterize a new standardized polytrauma model in rats based on the early molecular inflammatory and apoptotic response. Methods. Male Wistar rats (250 g, 6–10/group) were anesthetized and exposed to chest trauma (ChT), closed head injury (CHI), or Tib/Fib fracture including a soft tissue trauma (Fx + STT) or to the following combination of injuries: (1) ChT; (2) ChT + Fx + STT; (3) ChT + CHI; (4) CHI; (5) polytrauma (PT = ChT + CHI + Fx + STT). Sham-operated rats served as negative controls. The inflammatory response was quantified at 2 hours and 4 hours after trauma by analysis of “key” inflammatory mediators, including selected cytokines and complement components, in serum and bronchoalveolar (BAL) fluid samples. Results. Polytraumatized (PT) rats showed a significant systemic and intrapulmonary release of cytokines, chemokines, and complement anaphylatoxins, compared to rats with isolated injuries or selected combinations of injuries. Conclusion. This new rat model appears to closely mimic the early immunological response of polytrauma observed in humans and may provide a valid basis for evaluation of the complex pathophysiology and future therapeutic immune modulatory approaches in experimental polytrauma. PMID:22481866

The Sinorhizobium (Ensifer) fredii HH103 Type 3 Secretion System Suppresses Early Defense Responses to Effectively Nodulate Soybean.

PubMed

Jiménez-Guerrero, Irene; Pérez-Montaño, Francisco; Monreal, José Antonio; Preston, Gail M; Fones, Helen; Vioque, Blanca; Ollero, Francisco Javier; López-Baena, Francisco Javier

2015-07-01

Plants that interact with pathogenic bacteria in their natural environments have developed barriers to block or contain the infection. Phytopathogenic bacteria have evolved mechanisms to subvert these defenses and promote infection. Thus, the type 3 secretion system (T3SS) delivers bacterial effectors directly into the plant cells to alter host signaling and suppress defenses, providing an appropriate environment for bacterial multiplication. Some rhizobial strains possess a symbiotic T3SS that seems to be involved in the suppression of host defenses to promote nodulation and determine the host range. In this work, we show that the inactivation of the Sinorhizobium (Ensifer) fredii HH103 T3SS negatively affects soybean nodulation in the early stages of the symbiotic process, which is associated with a reduction of the expression of early nodulation genes. This symbiotic phenotype could be the consequence of the bacterial triggering of soybean defense responses associated with the production of salicylic acid (SA) and the impairment of the T3SS mutant to suppress these responses. Interestingly, the early induction of the transcription of GmMPK4, which negatively regulates SA accumulation and defense responses in soybean via WRKY33, could be associated with the differential defense responses induced by the parental and the T3SS mutant strain.

Early-life inflammation, immune response and ageing.

PubMed

Khan, Imroze; Agashe, Deepa; Rolff, Jens

2017-03-15

Age-related diseases are often attributed to immunopathology, which results in self-damage caused by an inappropriate inflammatory response. Immunopathology associated with early-life inflammation also appears to cause faster ageing, although we lack direct experimental evidence for this association. To understand the interactions between ageing, inflammation and immunopathology, we used the mealworm beetle Tenebrio molitor as a study organism. We hypothesized that phenoloxidase, an important immune effector in insect defence, may impose substantial immunopathological costs by causing tissue damage to Malpighian tubules (MTs; functionally equivalent to the human kidney), in turn accelerating ageing. In support of this hypothesis, we found that RNAi knockdown of phenoloxidase (PO) transcripts in young adults possibly reduced inflammation-induced autoreactive tissue damage to MTs, and increased adult lifespan. Our work thus suggests a causative link between immunopathological costs of early-life inflammation and faster ageing. We also reasoned that if natural selection weakens with age, older individuals should display increased immunopathological costs associated with an immune response. Indeed, we found that while old infected individuals cleared infection faster than young individuals, possibly they also displayed exacerbated immunopathological costs (larger decline in MT function) and higher post-infection mortality. RNAi-mediated knockdown of PO response partially rescued MTs function in older beetles and resulted in increased lifespan after infection. Taken together, our data are consistent with a direct role of immunopathological consequences of immune response during ageing in insects. Our work is also the first report that highlights the pervasive role of tissue damage under diverse contexts of ageing and immune response. © 2017 The Author(s).

Early-life inflammation, immune response and ageing

PubMed Central

2017-01-01

Age-related diseases are often attributed to immunopathology, which results in self-damage caused by an inappropriate inflammatory response. Immunopathology associated with early-life inflammation also appears to cause faster ageing, although we lack direct experimental evidence for this association. To understand the interactions between ageing, inflammation and immunopathology, we used the mealworm beetle Tenebrio molitor as a study organism. We hypothesized that phenoloxidase, an important immune effector in insect defence, may impose substantial immunopathological costs by causing tissue damage to Malpighian tubules (MTs; functionally equivalent to the human kidney), in turn accelerating ageing. In support of this hypothesis, we found that RNAi knockdown of phenoloxidase (PO) transcripts in young adults possibly reduced inflammation-induced autoreactive tissue damage to MTs, and increased adult lifespan. Our work thus suggests a causative link between immunopathological costs of early-life inflammation and faster ageing. We also reasoned that if natural selection weakens with age, older individuals should display increased immunopathological costs associated with an immune response. Indeed, we found that while old infected individuals cleared infection faster than young individuals, possibly they also displayed exacerbated immunopathological costs (larger decline in MT function) and higher post-infection mortality. RNAi-mediated knockdown of PO response partially rescued MTs function in older beetles and resulted in increased lifespan after infection. Taken together, our data are consistent with a direct role of immunopathological consequences of immune response during ageing in insects. Our work is also the first report that highlights the pervasive role of tissue damage under diverse contexts of ageing and immune response. PMID:28275145

Basic Fibroblast Growth Factor Activates Serum Response Factor Gene Expression by Multiple Distinct Signaling Mechanisms

PubMed Central

Spencer, Jeffrey A.; Major, Michael L.; Misra, Ravi P.

1999-01-01

Serum response factor (SRF) plays a central role in the transcriptional response of mammalian cells to a variety of extracellular signals. It is a key regulator of many cellular early response genes which are believed to be involved in cell growth and differentiation. The mechanism by which SRF activates transcription in response to mitogenic agents has been extensively studied; however, significantly less is known about regulation of the SRF gene itself. Previously, we identified distinct regulatory elements in the SRF promoter that play a role in activation, including a consensus ETS domain binding site, a consensus overlapping Sp/Egr-1 binding site, and two SRF binding sites. We further showed that serum induces SRF by a mechanism that requires an intact SRF binding site, also termed a CArG box. In the present study we demonstrate that in response to stimulation of cells by a purified growth factor, basic fibroblast growth factor (bFGF), the SRF promoter is upregulated by a complex pathway that involves at least two independent mechanisms: a CArG box-independent mechanism that is mediated by an ETS binding site, and a novel CArG box-dependent mechanism that requires both an Sp factor binding site and the CArG motifs for maximal stimulation. Our analysis indicates that the CArG/Sp element activation mechanism is mediated by distinct signaling pathways. The CArG box-dependent component is targeted by a Rho-mediated pathway, and the Sp binding site-dependent component is targeted by a Ras-mediated pathway. Both SRF and bFGF have been implicated in playing an important role in mediating cardiogenesis during development. The implications of our findings for SRF expression during development are discussed. PMID:10330138

RNA-Seq-based transcriptome profiling of early nitrogen deficiency response in cucumber seedlings provides new insight into the putative nitrogen regulatory network.

PubMed

Zhao, Wenchao; Yang, Xueyong; Yu, Hongjun; Jiang, Weijie; Sun, Na; Liu, Xiaoran; Liu, Xiaolin; Zhang, Xiaomeng; Wang, Yan; Gu, Xingfang

2015-03-01

Nitrogen (N) is both an important macronutrient and a signal for plant growth and development. However, the early regulatory mechanism of plants in response to N starvation is not well understood, especially in cucumber, an economically important crop that normally consumes excessive N during production. In this study, the early time-course transcriptome response of cucumber leaves under N deficiency was monitored using RNA sequencing (RNA-Seq). More than 23,000 transcripts were examined in cucumber leaves, of which 364 genes were differentially expressed in response to N deficiency. Based on the Kyoto Encyclopedia of Genes and Genomes (KEGG) pathway database, gene ontology (GO) and protein-protein interaction analysis, 64 signaling-related N-deficiency-responsive genes were identified. Furthermore, the potential regulatory mechanisms of anthocyanin accumulation, Chl decline and cell wall remodeling were assessed at the transcription level. Increased ascorbic acid synthesis was identified in cucumber seedlings and fruit under N-deficient conditions, and a new corresponding regulatory hypothesis has been proposed. A data cross-comparison between model plants and cucumber was made, and some common and specific N-deficient response mechanisms were found in the present study. Our study provides novel insights into the responses of cucumber to nitrogen starvation at the global transcriptome level, which are expected to be highly useful for dissecting the N response pathways in this major vegetable and for improving N fertilization practices. © The Author 2014. Published by Oxford University Press on behalf of Japanese Society of Plant Physiologists. All rights reserved. For permissions, please email: journals.permissions@oup.com.

The NRF2-KEAP1 Pathway Is an Early Responsive Gene Network in Arsenic Exposed Lymphoblastoid Cells

PubMed Central

Córdova, Emilio J.; Martínez-Hernández, Angélica; Uribe-Figueroa, Laura; Centeno, Federico; Morales-Marín, Mirna; Koneru, Harsha; Coleman, Matthew A.; Orozco, Lorena

2014-01-01

Inorganic arsenic (iAs), a major environmental contaminant, has risen as an important health problem worldwide. More detailed identification of the molecular mechanisms associated with iAs exposure would help to establish better strategies for prevention and treatment. Although chronic iAs exposures have been previously studied there is little to no information regarding the early events of exposure to iAs. To better characterize the early mechanisms of iAs exposure we conducted gene expression studies using sublethal doses of iAs at two different time-points. The major transcripts differentially regulated at 2 hrs of iAs exposure included antioxidants, detoxificants and chaperones. Moreover, after 12 hrs of exposure many of the down-regulated genes were associated with DNA replication and S phase cell cycle progression. Interestingly, the most affected biological pathway by both 2 or 12 hrs of iAs exposure were the Nrf2-Keap1 pathway, represented by the highly up-regulated HMOX1 transcript, which is transcriptionally regulated by the transcription factor Nrf2. Additional Nrf2 targets included SQSTM1 and ABCB6, which were not previously associated with acute iAs exposure. Signalling pathways such as interferon, B cell receptor and AhR route were also responsive to acute iAs exposure. Since HMOX1 expression increased early (20 min) and was responsive to low iAs concentrations (0.1 µM), this gene could be a suitable early biomarker for iAs exposure. In addition, the novel Nrf2 targets SQSTM1 and ABCB6 could play an important and previously unrecognized role in cellular protection against iAs. PMID:24516582

Diverse mechanisms evolved by DNA viruses to inhibit early host defenses

PubMed Central

Sheng, Xinlei; Song, Bokai; Cristea, Ileana M.

2016-01-01

In mammalian cells, early defenses against infection by pathogens are mounted through a complex network of signaling pathways shepherded by immune-modulatory pattern-recognition receptors. As obligate parasites, the survival of viruses is dependent upon the evolutionary acquisition of mechanisms that tactfully dismantle and subvert the cellular intrinsic and innate immune responses. Here, we review the diverse mechanisms by which viruses that accommodate DNA genomes are able to circumvent activation of cellular immunity. We start by discussing viral manipulation of host defense protein levels by either transcriptional regulation or protein degradation. We next review viral strategies used to repurpose or inhibit these cellular immune factors by molecular hijacking or by regulating their post-translational modification status. Additionally, we explore the infection-induced temporal modulation of apoptosis to facilitate viral replication and spread. Lastly, the co-evolution of viruses with their hosts is highlighted by the acquisition of elegant mechanisms for suppressing host defenses via viral mimicry of host factors. In closing, we present a perspective on how characterizing these viral evasion tactics both broadens the understanding of virus-host interactions and reveals essential functions of the immune system at the molecular level. This knowledge is critical in understanding the sources of viral pathogenesis, as well as for the design of antiviral therapeutics and autoimmunity treatments. PMID:27650455

Early skin toxicity predicts better outcomes, and early tumor shrinkage predicts better response after cetuximab treatment in advanced colorectal cancer.

PubMed

Kogawa, T; Doi, A; Shimokawa, M; Fouad, T M; Osuga, T; Tamura, F; Mizushima, T; Kimura, T; Abe, S; Ihara, H; Kukitsu, T; Sumiyoshi, T; Yoshizaki, N; Hirayama, M; Sasaki, T; Kawarada, Y; Kitashiro, S; Okushiba, S; Kondo, H; Tsuji, Y

2015-03-01

Cetuximab-containing treatments for metastatic colorectal cancer have been shown to have higher overall response rates and longer progression-free and overall survival than other systemic therapies. Cetuximab-related manifestations, including severe skin toxicity and early tumor shrinkage, have been shown to be predictors of response to cetuximab. We hypothesized that early skin toxicity is a predictor of response and better outcomes in patients with advanced colorectal carcinoma. We retrospectively evaluated 62 patients with colorectal adenocarcinoma who had unresectable tumors and were treated with cetuximab in our institution. Skin toxicity grade was evaluated on each treatment day. Tumor size was evaluated using computed tomography prior to treatment and 4-8 weeks after the start of treatment with cetuximab.Patients with early tumor shrinkage after starting treatment with cetuximab had a significantly higher overall response rate (P = 0.0001). Patients with early skin toxicity showed significantly longer overall survival (P = 0.0305), and patients with higher skin toxicity grades had longer progression-free survival (P = 0.0168).We have shown that early tumor shrinkage, early onset of skin toxicity, and high skin toxicity grade are predictors of treatment efficacy and/or outcome in patients with advanced colorectal carcinoma treated with cetuximab.

Mechanisms determining cholinergic neural responses in airways of young and mature rabbits.

PubMed

Larsen, Gary L; Loader, Joan; Nguyen, Dee Dee; Fratelli, Cori; Dakhama, Azzeddine; Colasurdo, Giuseppe N

2004-08-01

Neural pathways help control airway caliber and responsiveness. Yet little is known of how neural control changes as a function of development. In rabbits, we found electrical field stimulation (EFS) of airway nerves led to more marked contractile responses in 2- vs. 13-week-old animals. This enhanced response to EFS may be due to prejunctional, junctional, and/or postjunctional neural mechanisms. We assessed these mechanisms in airways of 2- and 13-week-old rabbits. The contractile responses to methacholine did not differ in the groups, suggesting postjunctional neural events are not primarily responsible for differing responses to EFS. To address junctional events, acetylcholinesterase (AChE) was measured (spectrophotometry). AChE was elevated in 2-week-olds. However, this should lead to less and not greater responses. Prejunctionally, EFS-induced acetylcholine (ACh) release was assessed by HPLC. Airways of 2-week-old rabbits released significantly more ACh than airways from mature rabbits. Choline acetyltransferase, a marker of cholinergic nerves, was not different between groups, suggesting that more ACh release in young rabbits was not due to increased nerve density. ACh release in the presence of polyarginine increased significantly in both groups, supporting the presence of functional muscarinic autoreceptors (M2) at both ages. Because substance P (SP) increases release of ACh, SP was measured by ELISA. This neuropeptide was significantly elevated in airways of younger rabbits. Nerve growth factor (NGF) increased SP and was also significantly increased in airways from younger rabbits. This work suggests that increases in EFS-induced responsiveness in young rabbits are likely due to prejunctional events with enhanced release of ACh. Increases in NGF and SP early in life may contribute to this increased responsiveness. Copyright 2004 Wiley-Liss, Inc.

The neural mechanisms of semantic and response conflicts: an fMRI study of practice-related effects in the Stroop task.

PubMed

Chen, Zhencai; Lei, Xu; Ding, Cody; Li, Hong; Chen, Antao

2013-02-01

Previous studies have demonstrated that there are separate neural mechanisms underlying semantic and response conflicts in the Stroop task. However, the practice effects of these conflicts need to be elucidated and the possible involvements of common neural mechanisms are yet to be established. We employed functional magnetic resonance imaging (fMRI) in a 4-2 mapping practice-related Stroop task to determine the neural substrates under these conflicts. Results showed that different patterns of brain activations are associated with practice in the attentional networks (e.g., dorsolateral prefrontal cortex (DLPFC), anterior cingulate cortex (ACC), and posterior parietal cortex (PPC)) for both conflicts, response control regions (e.g., inferior frontal junction (IFJ), inferior frontal gyrus (IFG)/insula, and pre-supplementary motor areas (pre-SMA)) for semantic conflict, and posterior cortex for response conflict. We also found areas of common activation in the left hemisphere within the attentional networks, for the early practice stage in semantic conflict and the late stage in "pure" response conflict using conjunction analysis. The different practice effects indicate that there are distinct mechanisms underlying these two conflict types: semantic conflict practice effects are attributable to the automation of stimulus processing, conflict and response control; response conflict practice effects are attributable to the proportional increase of conflict-related cognitive resources. In addition, the areas of common activation suggest that the semantic conflict effect may contain a partial response conflict effect, particularly at the beginning of the task. These findings indicate that there are two kinds of response conflicts contained in the key-pressing Stroop task: the vocal-level (mainly in the early stage) and key-pressing (mainly in the late stage) response conflicts; thus, the use of the subtraction method for the exploration of semantic and response conflicts

Istanbul Earthquake Early Warning and Rapid Response System

NASA Astrophysics Data System (ADS)

Erdik, M. O.; Fahjan, Y.; Ozel, O.; Alcik, H.; Aydin, M.; Gul, M.

2003-12-01

As part of the preparations for the future earthquake in Istanbul a Rapid Response and Early Warning system in the metropolitan area is in operation. For the Early Warning system ten strong motion stations were installed as close as possible to the fault zone. Continuous on-line data from these stations via digital radio modem provide early warning for potentially disastrous earthquakes. Considering the complexity of fault rupture and the short fault distances involved, a simple and robust Early Warning algorithm, based on the exceedance of specified threshold time domain amplitude levels is implemented. The band-pass filtered accelerations and the cumulative absolute velocity (CAV) are compared with specified threshold levels. When any acceleration or CAV (on any channel) in a given station exceeds specific threshold values it is considered a vote. Whenever we have 2 station votes within selectable time interval, after the first vote, the first alarm is declared. In order to specify the appropriate threshold levels a data set of near field strong ground motions records form Turkey and the world has been analyzed. Correlations among these thresholds in terms of the epicenter distance the magnitude of the earthquake have been studied. The encrypted early warning signals will be communicated to the respective end users by UHF systems through a "service provider" company. The users of the early warning signal will be power and gas companies, nuclear research facilities, critical chemical factories, subway system and several high-rise buildings. Depending on the location of the earthquake (initiation of fault rupture) and the recipient facility the alarm time can be as high as about 8s. For the rapid response system one hundred 18 bit-resolution strong motion accelerometers were placed in quasi-free field locations (basement of small buildings) in the populated areas of the city, within an area of approximately 50x30km, to constitute a network that will enable early

A linear chromatic mechanism drives the pupillary response.

PubMed Central

Tsujimura, S.; Wolffsohn, J. S.; Gilmartin, B.

2001-01-01

Previous studies have shown that a chromatic mechanism can drive pupil responses. The aim of this research was to clarify whether a linear or nonlinear chromatic mechanism drives pupillary responses by using test stimuli of various colours that are defined in cone contrast space. The pupil and accommodation responses evoked by these test stimuli were continuously and simultaneously objectively measured by photorefraction. The results with isochromatic and isoluminant stimuli showed that the accommodative level remained approximately constant (< 0.25 D change in mean level) even when the concurrent pupillary response was large (ca. 0.30 mm). The pupillary response to an isoluminant grating was sustained, delayed (by ca. 60 ms) and larger in amplitude than that for a isochromatic uniform stimulus, which supports previous work suggesting that the chromatic mechanism contributes to the pupillary response. In a second experiment, selected chromatic test gratings were used and isoresponse contours in cone contrast space were obtained. The results showed that the isoresponse contour in cone contrast space is well described (r(2) = 0.99) by a straight line with a positive slope. The results indicate that a /L - M/ linear chromatic mechanism, whereby a signal from the long wavelength cone is subtracted from that of the middle wavelength cone and vice versa, drives pupillary responses. PMID:11674867

Discrimination of timbre in early auditory responses of the human brain.

PubMed

Seol, Jaeho; Oh, MiAe; Kim, June Sic; Jin, Seung-Hyun; Kim, Sun Il; Chung, Chun Kee

2011-01-01

The issue of how differences in timbre are represented in the neural response still has not been well addressed, particularly with regard to the relevant brain mechanisms. Here we employ phasing and clipping of tones to produce auditory stimuli differing to describe the multidimensional nature of timbre. We investigated the auditory response and sensory gating as well, using by magnetoencephalography (MEG). Thirty-five healthy subjects without hearing deficit participated in the experiments. Two different or same tones in timbre were presented through conditioning (S1)-testing (S2) paradigm as a pair with an interval of 500 ms. As a result, the magnitudes of auditory M50 and M100 responses were different with timbre in both hemispheres. This result might support that timbre, at least by phasing and clipping, is discriminated in the auditory early processing. The second response in a pair affected by S1 in the consecutive stimuli occurred in M100 of the left hemisphere, whereas both M50 and M100 responses to S2 only in the right hemisphere reflected whether two stimuli in a pair were the same or not. Both M50 and M100 magnitudes were different with the presenting order (S1 vs. S2) for both same and different conditions in the both hemispheres. Our results demonstrate that the auditory response depends on timbre characteristics. Moreover, it was revealed that the auditory sensory gating is determined not by the stimulus that directly evokes the response, but rather by whether or not the two stimuli are identical in timbre.

The Long-term Impact of Early Life Pain On Adult Responses to Anxiety and Stress: Historical Perspectives and Empirical Evidence

PubMed Central

Victoria, Nicole C.; Murphy, Anne Z.

2016-01-01

Approximately 1 in 6 infants are born prematurely each year. Typically, these infants spend 25 days in the Neonatal Intensive Care Unit (NICU) where they experience 10–18 painful and inflammatory procedures each day. Remarkably, pre-emptive analgesics and/or anesthesia are administered less than 25% of the time. Unalleviated pain during the perinatal period is associated with permanent decreases in pain sensitivity, blunted cortisol responses and high rates of neuropsychiatric disorders. To date, the mechanism(s) by which these long-term changes in stress and pain behavior occur, and whether such alterations can be prevented by appropriate analgesia at the time of insult, remains unclear. Work in our lab using a rodent model of early life pain suggests that inflammatory pain experienced on the day of birth blunts adult responses to stress- and pain-provoking stimuli, and dysregulates the hypothalamic pituitary adrenal (HPA) axis in part through a permanent upregulation in central endogenous opioid tone. This review focuses on the long-term impact of neonatal inflammatory pain on adult anxiety- and stress-related responses, and underlying neuroanatomical changes in the context of endogenous pain control and the HPA axis. These two systems are in a state of exaggerated developmental plasticity early in postnatal life, and work in concert to respond to noxious or aversive stimuli. We present empirical evidence from animal and clinical studies, and discuss historical perspectives underlying the lack of analgesia/anesthetic use for early life pain in the modern NICU. PMID:26210872

Experimental acidification of Little Rock Lake (Wisconsin): fish research approach and early responses.

PubMed

Swenson, W A; McCormick, J H; Simonson, T D; Jensen, K M; Eaton, J G

1989-01-01

One goal of research at Little Rock Lake, Wisconsin, is to enhance understanding of lake acidification effects on warm- and cool-water fishery resources. The Little Rock Lake fish assemblage is characteristic of many acid sensitive waters in North America and is dominated by yellow perch (Percidae) and sunfishes (Centrarchidae). Analyses of reproduction, early survival and growth rates in the field were designed around the differing reproductive modes of these taxa. Complementary laboratory research on early life stages was conducted to assist in isolating direct effect mechanisms and to determine the reliability of laboratory results in predicting field response. Preliminary findings suggest that lake acidification to pH 5.6 has not influenced reproductive activity of the four most abundant fish species. However, the field results suggest that year-class failure of rock bass (Ambloplites rupestris) may be occurring due to reduced survival of early life stages. Reduced growth and food conversion efficiency of Age 0 largemouth bass (Micropterus salmoides) is also suggested. The laboratory bioassays indicate rock bass is the most acid-sensitive Little Rock Lake species tested. However, rock bass fry survival was not significantly affected until pH was reduced from 5.6 to 5.0.

SOS response activation and competence development are antagonistic mechanisms in Streptococcus thermophilus.

PubMed

Boutry, Céline; Delplace, Brigitte; Clippe, André; Fontaine, Laetitia; Hols, Pascal

2013-02-01

Streptococcus includes species that either contain or lack the LexA-like repressor (HdiR) of the classical SOS response. In Streptococcus pneumoniae, a species which belongs to the latter group, SOS response inducers (e.g., mitomycin C [Mc] and fluoroquinolones) were shown to induce natural transformation, leading to the hypothesis that DNA damage-induced competence could contribute to genomic plasticity and stress resistance. Using reporter strains and microarray experiments, we investigated the impact of the SOS response inducers mitomycin C and norfloxacin and the role of HdiR on competence development in Streptococcus thermophilus. We show that both the addition of SOS response inducers and HdiR inactivation have a dual effect, i.e., induction of the expression of SOS genes and reduction of transformability. Reduction of transformability results from two different mechanisms, since HdiR inactivation has no major effect on the expression of competence (com) genes, while mitomycin C downregulates the expression of early and late com genes in a dose-dependent manner. The downregulation of com genes by mitomycin C was shown to take place at the level of the activation of the ComRS signaling system by an unknown mechanism. Conversely, we show that a ComX-deficient strain is more resistant to mitomycin C and norfloxacin in a viability plate assay, which indicates that competence development negatively affects the resistance of S. thermophilus to DNA-damaging agents. Altogether, our results strongly suggest that SOS response activation and competence development are antagonistic processes in S. thermophilus.

Early feeding and early life housing conditions influence the response towards a noninfectious lung challenge in broilers.

PubMed

Simon, K; de Vries Reilingh, G; Bolhuis, J E; Kemp, B; Lammers, A

2015-09-01

Early life conditions such as feed and water availability immediately post hatch (PH) and housing conditions may influence immune development and therefore immune reactivity later in life. The current study addressed the consequences of a combination of these 2 early life conditions for immune reactivity, i.e., the specific antibody response towards a non-infectious lung challenge. Broiler chicks received feed and water either immediately p.h. or with a 72 h delay and were either reared in a floor or a cage system. At 4 weeks of age, chicks received either an intra-tracheally administered Escherichia coli lipopolysaccharide (LPS)/Human Serum Albumin (HUSA) challenge or a placebo, and antibody titers were measured up to day 14 after administration of the challenge. Chicks housed on the floor and which had a delayed access to feed p.h. showed the highest antibody titers against HuSA. These chicks also showed the strongest sickness response and poorest performance in response to the challenge, indicating that chicks with delayed access to feed might be more sensitive to an environment with higher antigenic pressure. In conclusion, results from the present study show that early life feeding strategy and housing conditions influence a chick's response to an immune challenge later in life. These 2 early life factors should therefore be taken into account when striving for a balance between disease resistance and performance in poultry. © 2015 Poultry Science Association Inc.

Early mechanical stimulation only permits timely bone healing in sheep.

PubMed

Tufekci, Pelin; Tavakoli, Aramesh; Dlaska, Constantin; Neumann, Mirjam; Shanker, Mihir; Saifzadeh, Siamak; Steck, Roland; Schuetz, Michael; Epari, Devakar

2018-06-01

Bone fracture healing is sensitive to the fixation stability. However, it is unclear which phases of healing are mechano-sensitive and if mechanical stimulation is required throughout repair. In this study, a novel bone defect model, which isolates an experimental fracture from functional loading, was applied in sheep to investigate if stimulation limited to the early proliferative phase is sufficient for bone healing. An active fixator controlled motion in the fracture. Animals of the control group were unstimulated. In the physiological-like group, 1 mm axial compressive movements were applied between day 5 and 21, thereafter the movements were decreased in weekly increments and stopped after 6 weeks. In the early stimulatory group, the movements were stopped after 3 weeks. The experimental fractures were evaluated with mechanical and micro-computed tomography methods after 9 weeks healing. The callus strength of the stimulated fractures (physiological-like and early stimulatory) was greater than the unstimulated control group. The control group was characterized by minimal external callus formation and a lack of bone bridging at 9 weeks. In contrast, the stimulated groups exhibited advanced healing with solid bone formation across the defect. This was confirmed quantitatively by a lower bone volume in the control group compared to the stimulated groups.The novel experimental model permits the application of a well-defined load history to an experimental bone fracture. The poor healing observed in the control group is consistent with under-stimulation. This study has shown early mechanical stimulation only is sufficient for a timely healing outcome. © 2017 Orthopaedic Research Society. Published by Wiley Periodicals, Inc. J Orthop Res 36:1790-1796, 2018. © 2017 Orthopaedic Research Society. Published by Wiley Periodicals, Inc.

Experimental Study on the Coupling Mechanism of Early-strength Backfill and Rock

NASA Astrophysics Data System (ADS)

Wang, Mingxu

2017-11-01

In order to study the interaction mechanism between the ore rock and backfill at the early stage, paraffin is chosen as the cementing agent. Based on the damage mechanics and fractal theory, the interaction mechanism between the ore rock and backfill is characterized by the relevant tests on the complex of proportioned ore rock and backfill with resistance strain gauge, crack propagation, microscopic imaging and AE. The experimental results showed that: 1) Through the axial loading test, compared with the early strength of the cemented filling and paraffin mechanical deformation characteristics, the stress and strain curves of the two had a common linear deformation law, while in the early strength of the filling elastic capacity strong, with a certain degree of resilience. 2) The bearing capacity of the backfill was weak, but the deformation ability was strong. During the bearing process, the deformation of the upper load was mainly caused by the ore rock, which leaded to the damage of the rock. 3) The distribution of AE points during the co-carrying of the filling and the ore rock was monitored by the acoustic emission instrument. The damage occurred mainly in the contact zone between the backfill and the ore rock zone. The corresponding AE point distribution also validated the crack happening.

Early-life adversity programs emotional functions and the neuroendocrine stress system: the contribution of nutrition, metabolic hormones and epigenetic mechanisms.

PubMed

Yam, Kit-Yi; Naninck, Eva F G; Schmidt, Mathias V; Lucassen, Paul J; Korosi, Aniko

2015-01-01

Clinical and pre-clinical studies have shown that early-life adversities, such as abuse or neglect, can increase the vulnerability to develop psychopathologies and cognitive decline later in life. Remarkably, the lasting consequences of stress during this sensitive period on the hypothalamic-pituitary-adrenal axis and emotional function closely resemble the long-term effects of early malnutrition and suggest a possible common pathway mediating these effects. During early-life, brain development is affected by both exogenous factors, like nutrition and maternal care as well as by endogenous modulators including stress hormones. These elements, while mostly considered for their independent actions, clearly do not act alone but rather in a synergistic manner. In order to better understand how the programming by early-life stress takes place, it is important to gain further insight into the exact interplay of these key elements, the possible common pathways as well as the underlying molecular mechanisms that mediate their effects. We here review evidence that exposure to both early-life stress and early-life under-/malnutrition similarly lead to life-long alterations on the neuroendocrine stress system and modify emotional functions. We further discuss how the different key elements of the early-life environment interact and affect one another and next suggest a possible role for the early-life adversity induced alterations in metabolic hormones and nutrient availability in shaping later stress responses and emotional function throughout life, possibly via epigenetic mechanisms. Such knowledge will help to develop intervention strategies, which gives the advantage of viewing the synergistic action of a more complete set of changes induced by early-life adversity.

Generative Mechanisms in Early Childhood Interventions: A Confirmatory Research Framework for Prevention.

PubMed

Reynolds, Arthur J; Ou, Suh-Ruu

2016-10-01

This article reviews methodological and analytic approaches and impact evidence for understanding the mechanisms of effects of early childhood interventions, including delinquency and violence prevention. Illustrations from longitudinal studies of preschool preventive interventions are provided. We restrict our attention to preventive interventions for children from birth to age 5, including evidence from the Chicago Longitudinal Study (CLS), which investigates the impact of an established school-based early childhood intervention. Frameworks and evidence will be organized according to the Five-Hypothesis Model (5HM), which postulates that a variety of early childhood interventions impact later well-being through the promotion of cognitive and scholastic advantages, motivational advantages, social adjustment, family support behaviors, and school supports. Recommendations are made for advancing confirmatory approaches for identifying the most effective prevention programs using identification of generative mechanisms as a major methodological criterion.

Generative Mechanisms in Early Childhood Interventions: A Confirmatory Research Framework for Prevention

PubMed Central

Reynolds, Arthur J.; Ou, Suh-Ruu

2015-01-01

This article reviews methodological and analytic approaches, and impact evidence for understanding the mechanisms of effects of early childhood interventions, including delinquency and violence prevention. Illustrations from longitudinal studies of preschool preventive interventions are provided. We restrict our attention to preventive interventions for children from birth to age 5, including evidence from the Chicago Longitudinal Study (CLS), which investigates the impact of an established school-based early childhood intervention. Frameworks and evidence will be organized according to the 5-Hypothesis Model (5HM), which postulates that a variety of early childhood interventions impact later well-being through the promotion of cognitive and scholastic advantages, motivational advantages, social adjustment, family support behaviors, and school supports. Recommendations are made for advancing confirmatory approaches for identifying the most effective prevention programs using identification of generative mechanisms as a major methodological criterion. PMID:26497315

Growth plate cartilage shows different strain patterns in response to static versus dynamic mechanical modulation.

PubMed

Kaviani, Rosa; Londono, Irene; Parent, Stefan; Moldovan, Florina; Villemure, Isabelle

2016-08-01

Longitudinal growth of long bones and vertebrae occurs in growth plate cartilage. This process is partly regulated by mechanical forces, which are one of the underlying reasons for progression of growth deformities such as idiopathic adolescent scoliosis and early-onset scoliosis. This concept of mechanical modulation of bone growth is also exploited in the development of fusionless treatments of these deformities. However, the optimal loading condition for the mechanical modulation of growth plate remains to be identified. The objective of this study was to evaluate the effects of in vitro static versus dynamic modulation and of dynamic loading parameters, such as frequency and amplitude, on the mechanical responses and histomorphology of growth plate explants. Growth plate explants from distal ulnae of 4-week-old swines were extracted and randomly distributed among six experimental groups: baseline ([Formula: see text]), control ([Formula: see text]), static ([Formula: see text]) and dynamic ([Formula: see text]). For static and dynamic groups, mechanical modulation was performed in vitro using an Indexed CartiGen bioreactor. A stress relaxation test combined with confocal microscopy and digital image correlation was used to characterize the mechanical responses of each explant in terms of peak stress, equilibrium stress, equilibrium modulus of elasticity and strain pattern. Histomorphometrical measurements were performed on toluidine blue tissue sections using a semi-automatic custom-developed MATLAB toolbox. Results suggest that compared to dynamic modulation, static modulation changes the strain pattern of the tissue and thus is more detrimental for tissue biomechanics, while the histomorphological parameters are not affected by mechanical modulation. Also, under dynamic modulation, changing the frequency or amplitude does not affect the biomechanical response of the tissue. Results of this study will be useful in finding optimal and non-damaging parameters

Early detection of changes in lung mechanics with oscillometry following bariatric surgery in severe obesity.

PubMed

Peters, Ubong; Hernandez, Paul; Dechman, Gail; Ellsmere, James; Maksym, Geoffrey

2016-05-01

Obesity is associated with respiratory symptoms that are reported to improve with weight loss, but this is poorly reflected in spirometry, and few studies have measured respiratory mechanics with oscillometry. We investigated whether early changes in lung mechanics following weight loss are detectable with oscillometry. Furthermore, we investigated whether the changes in lung mechanics measured in the supine position following weight loss are associated with changes in sleep quality. Nineteen severely obese female subjects (mean body mass index, 47.2 ± 6.6 kg/m(2)) were evaluated using spirometry, oscillometry, plethysmography, and the Pittsburgh Sleep Quality Index before and 5 weeks after bariatric surgery. These tests were conducted in both the upright and the supine position, and pre- and postbronchodilation with 200 μg of salbutamol. Five weeks after surgery, weight loss of 11.5 ± 2.5 kg was not associated with changes in spirometry and plethysmography, with the exception of functional residual capacity. There were also no changes in upright respiratory system resistance (Rrs) or reactance following weight loss. Importantly, however, in the supine position, weight loss caused a substantial reduction in Rrs. In addition, sleep quality improved significantly and was highly correlated with the reduction in supine Rrs. Prior to weight loss, subjects did not respond to the bronchodilator when assessed in the upright position with either spirometry or oscillometry; however, with modest weight loss, bronchodilator responsiveness returned to the normal range. Improvements in lung mechanics occur very early after weight loss, mostly in the supine position, resulting in improved sleep quality. These improvements are detectable with oscillometry but not with spirometry.

Auditory-neurophysiological responses to speech during early childhood: Effects of background noise

PubMed Central

White-Schwoch, Travis; Davies, Evan C.; Thompson, Elaine C.; Carr, Kali Woodruff; Nicol, Trent; Bradlow, Ann R.; Kraus, Nina

2015-01-01

Early childhood is a critical period of auditory learning, during which children are constantly mapping sounds to meaning. But learning rarely occurs under ideal listening conditions—children are forced to listen against a relentless din. This background noise degrades the neural coding of these critical sounds, in turn interfering with auditory learning. Despite the importance of robust and reliable auditory processing during early childhood, little is known about the neurophysiology underlying speech processing in children so young. To better understand the physiological constraints these adverse listening scenarios impose on speech sound coding during early childhood, auditory-neurophysiological responses were elicited to a consonant-vowel syllable in quiet and background noise in a cohort of typically-developing preschoolers (ages 3–5 yr). Overall, responses were degraded in noise: they were smaller, less stable across trials, slower, and there was poorer coding of spectral content and the temporal envelope. These effects were exacerbated in response to the consonant transition relative to the vowel, suggesting that the neural coding of spectrotemporally-dynamic speech features is more tenuous in noise than the coding of static features—even in children this young. Neural coding of speech temporal fine structure, however, was more resilient to the addition of background noise than coding of temporal envelope information. Taken together, these results demonstrate that noise places a neurophysiological constraint on speech processing during early childhood by causing a breakdown in neural processing of speech acoustics. These results may explain why some listeners have inordinate difficulties understanding speech in noise. Speech-elicited auditory-neurophysiological responses offer objective insight into listening skills during early childhood by reflecting the integrity of neural coding in quiet and noise; this paper documents typical response properties

Altered Evoked Gamma-Band Responses Reveal Impaired Early Visual Processing in ADHD Children

ERIC Educational Resources Information Center

Lenz, Daniel; Krauel, Kerstin; Flechtner, Hans-Henning; Schadow, Jeanette; Hinrichs, Hermann; Herrmann, Christoph S.

2010-01-01

Neurophysiological studies yield contrary results whether attentional problems of patients with attention-deficit/hyperactivity disorder (ADHD) are related to early visual processing deficits or not. Evoked gamma-band responses (GBRs), being among the first cortical responses occurring as early as 90 ms after visual stimulation in human EEG, have…

Mechanism and non-mechanism based imaging biomarkers for assessing biological response to treatment in non-small cell lung cancer.

PubMed

Weller, A; O'Brien, M E R; Ahmed, M; Popat, S; Bhosle, J; McDonald, F; Yap, T A; Du, Y; Vlahos, I; deSouza, N M

2016-05-01

Therapeutic options in locally advanced non-small cell lung cancer (NSCLC) have expanded in the past decade to include a palate of targeted interventions such as high dose targeted thermal ablations, radiotherapy and growing platform of antibody and small molecule therapies and immunotherapies. Although these therapies have varied mechanisms of action, they often induce changes in tumour architecture and microenvironment such that response is not always accompanied by early reduction in tumour mass, and evaluation by criteria other than size is needed to report more effectively on response. Functional imaging techniques, which probe the tumour and its microenvironment through novel positron emission tomography and magnetic resonance imaging techniques, offer more detailed insights into and quantitation of tumour response than is available on anatomical imaging alone. Use of these biomarkers, or other rational combinations as readouts of pathological response in NSCLC have potential to provide more accurate predictors of treatment outcomes. In this article, the robustness of the more commonly available positron emission tomography and magnetic resonance imaging biomarker indices is examined and the evidence for their application in NSCLC is reviewed. Copyright © 2016 Elsevier Ltd. All rights reserved.

The long-term impact of early life pain on adult responses to anxiety and stress: Historical perspectives and empirical evidence.

PubMed

Victoria, Nicole C; Murphy, Anne Z

2016-01-01

Approximately 1 in 6 infants are born prematurely each year. Typically, these infants spend 25 days in the Neonatal Intensive Care Unit (NICU) where they experience 10-18 painful and inflammatory procedures each day. Remarkably, pre-emptive analgesics and/or anesthesia are administered less than 25% of the time. Unalleviated pain during the perinatal period is associated with permanent decreases in pain sensitivity, blunted cortisol responses and high rates of neuropsychiatric disorders. To date, the mechanism(s) by which these long-term changes in stress and pain behavior occur, and whether such alterations can be prevented by appropriate analgesia at the time of insult, remains unclear. Work in our lab using a rodent model of early life pain suggests that inflammatory pain experienced on the day of birth blunts adult responses to stress- and pain-provoking stimuli, and dysregulates the hypothalamic pituitary adrenal (HPA) axis in part through a permanent upregulation in central endogenous opioid tone. This review focuses on the long-term impact of neonatal inflammatory pain on adult anxiety- and stress-related responses, and underlying neuroanatomical changes in the context of endogenous pain control and the HPA axis. These two systems are in a state of exaggerated developmental plasticity early in postnatal life, and work in concert to respond to noxious or aversive stimuli. We present empirical evidence from animal and clinical studies, and discuss historical perspectives underlying the lack of analgesia/anesthetic use for early life pain in the modern NICU. Copyright © 2015 Elsevier Inc. All rights reserved.

Vestibular Activation Differentially Modulates Human Early Visual Cortex and V5/MT Excitability and Response Entropy

PubMed Central

Guzman-Lopez, Jessica; Arshad, Qadeer; Schultz, Simon R; Walsh, Vincent; Yousif, Nada

2013-01-01

Head movement imposes the additional burdens on the visual system of maintaining visual acuity and determining the origin of retinal image motion (i.e., self-motion vs. object-motion). Although maintaining visual acuity during self-motion is effected by minimizing retinal slip via the brainstem vestibular-ocular reflex, higher order visuovestibular mechanisms also contribute. Disambiguating self-motion versus object-motion also invokes higher order mechanisms, and a cortical visuovestibular reciprocal antagonism is propounded. Hence, one prediction is of a vestibular modulation of visual cortical excitability and indirect measures have variously suggested none, focal or global effects of activation or suppression in human visual cortex. Using transcranial magnetic stimulation-induced phosphenes to probe cortical excitability, we observed decreased V5/MT excitability versus increased early visual cortex (EVC) excitability, during vestibular activation. In order to exclude nonspecific effects (e.g., arousal) on cortical excitability, response specificity was assessed using information theory, specifically response entropy. Vestibular activation significantly modulated phosphene response entropy for V5/MT but not EVC, implying a specific vestibular effect on V5/MT responses. This is the first demonstration that vestibular activation modulates human visual cortex excitability. Furthermore, using information theory, not previously used in phosphene response analysis, we could distinguish between a specific vestibular modulation of V5/MT excitability from a nonspecific effect at EVC. PMID:22291031

Early Change in Stroke Size Performs Best in Predicting Response to Therapy.

PubMed

Simpkins, Alexis Nétis; Dias, Christian; Norato, Gina; Kim, Eunhee; Leigh, Richard

2017-01-01

Reliable imaging biomarkers of response to therapy in acute stroke are needed. The final infarct volume and percent of early reperfusion have been used for this purpose. Early fluctuation in stroke size is a recognized phenomenon, but its utility as a biomarker for response to therapy has not been established. This study examined the clinical relevance of early change in stroke volume and compared it with the final infarct volume and percent of early reperfusion in identifying early neurologic improvement (ENI). Acute stroke patients, enrolled between 2013 and 2014 with serial magnetic resonance imaging (MRI) scans (pretreatment baseline, 2 h post, and 24 h post), who received thrombolysis were included in the analysis. Early change in stroke volume, infarct volume at 24 h on diffusion, and percent of early reperfusion were calculated from the baseline and 2 h MRI scans were compared. ENI was defined as ≥4 point decrease in National Institutes of Health Stroke Scales within 24 h. Logistic regression models and receiver operator characteristics analysis were used to compare the efficacy of 3 imaging biomarkers. Serial MRIs of 58 acute stroke patients were analyzed. Early change in stroke volume was significantly associated with ENI by logistic regression analysis (OR 0.93, p = 0.048) and remained significant after controlling for stroke size and severity (OR 0.90, p = 0.032). Thus, for every 1 mL increase in stroke volume, there was a 10% decrease in the odds of ENI, while for every 1 mL decrease in stroke volume, there was a 10% increase in the odds of ENI. Neither infarct volume at 24 h nor percent of early reperfusion were significantly associated with ENI by logistic regression. Receiver-operator characteristic analysis identified early change in stroke volume as the only biomarker of the 3 that performed significantly different than chance (p = 0.03). Early fluctuations in stroke size may represent a more reliable biomarker for response to therapy than the

Evidence for two concurrent inhibitory mechanisms during response preparation

PubMed Central

Duque, Julie; Lew, David; Mazzocchio, Riccardo; Olivier, Etienne; Ivry, Richard B.

2010-01-01

Inhibitory mechanisms are critically involved in goal-directed behaviors. To gain further insight into how such mechanisms shape motor representations during response preparation, motor evoked potentials (MEPs) elicited by transcranial magnetic stimulation (TMS) and H-reflexes were recorded from left hand muscles during choice reaction time tasks. The imperative signal, which indicated the required response, was always preceded by a preparatory cue. During the post-cue delay period, left MEPs were suppressed when the left hand had been cued for the forthcoming response, suggestive of a form of inhibition specifically directed at selected response representations. H-reflexes were also suppressed on these trials, indicating that the effects of this inhibition extend to spinal circuits. In addition, left MEPs were suppressed when the right hand was cued, but only when left hand movements were a possible response option before the onset of the cue. Notably, left hand H-reflexes were not modulated on these trials, consistent with a cortical locus of inhibition that lowers the activation of task-relevant, but non-selected responses. These results suggest the concurrent operation of two inhibitory mechanisms during response preparation: one decreases the activation of selected responses at the spinal level, helping to control when selected movements should be initiated by preventing their premature release; a second, upstream mechanism helps to determine what response to make during a competitive selection process. PMID:20220014

Study on the early warning mechanism for the security of blast furnace hearths

NASA Astrophysics Data System (ADS)

Zhao, Hong-bo; Huo, Shou-feng; Cheng, Shu-sen

2013-04-01

The campaign life of blast furnace (BF) hearths has become the limiting factor for safety and high efficiency production of modern BFs. However, the early warning mechanism of hearth security has not been clear. In this article, based on heat transfer calculations, heat flux and erosion monitoring, the features of heat flux and erosion were analyzed and compared among different types of hearths. The primary detecting elements, mathematical models, evaluating standards, and warning methods were discussed. A novel early warning mechanism with the three-level quantificational standards was proposed for BF hearth security.

Dual function of CD70 in viral infection: modulator of early cytokine responses and activator of adaptive responses1

PubMed Central

Allam, Atef; Swiecki, Melissa; Vermi, William; Ashwell, Jonathan D.; Colonna, Marco

2014-01-01

The role of the tumor necrosis factor family member CD70 in adaptive T cell responses has been intensively studied but its function in innate responses is still under investigation. Here we show that CD70 inhibits the early innate response to murine cytomegalovirus (MCMV) but is essential for the optimal generation of virus-specific CD8 T cells. CD70-/- mice reacted to MCMV infection with a robust type I interferon and proinflammatory cytokine response. This response was sufficient for initial control of MCMV, although at later time points, CD70-/- mice became more susceptible to MCMV infection. The heightened cytokine response during the early phase of MCMV infection in CD70-/- mice was paralleled by a reduction in regulatory T cells (Treg). Treg from naïve CD70-/- mice were not as efficient at suppressing T cell proliferation compared to Treg from naïve WT mice and depletion of Treg during MCMV infection in Foxp3-DTR mice or in WT mice recapitulated the phenotype observed in CD70-/- mice. Our study demonstrates that while CD70 is required for the activation of the antiviral adaptive response, it has a regulatory role in early cytokine responses to viruses such as MCMV, possibly through maintenance of Treg survival and function. PMID:24913981

Effects of early-life malnutrition on neurodevelopment and neuropsychiatric disorders and the potential mechanisms.

PubMed

Yan, Xintian; Zhao, Xinzhi; Li, Juxue; He, Lin; Xu, Mingqing

2018-04-20

Lines of evidence have demonstrated that early-life malnutrition is highly correlated with neurodevelopment and adulthood neuropsychiatric disorders, while some findings are conflicting with each other. In addition, the biological mechanisms are less investigated. We systematically reviewed the evidence linking early-life nutrition status with neurodevelopment and clinical observations in human and animal models. We summarized the effects of special nutritious on neuropsychiatric disorders and explored the underlying potential mechanisms. The further understanding of the biological regulation of early-life nutritional status on neurodevelopment might shed light on precision nutrition at an integrative systems biology framework. Copyright © 2018 Elsevier Inc. All rights reserved.

Postpartum Circulating Markers of Inflammation and the Systemic Acute-Phase Response After Early-Onset Preeclampsia.

PubMed

van Rijn, Bas B; Bruinse, Hein W; Veerbeek, Jan H; Post Uiterweer, Emiel D; Koenen, Steven V; van der Bom, Johanna G; Rijkers, Ger T; Roest, Mark; Franx, Arie

2016-02-01

Preeclampsia is an inflammatory-mediated hypertensive disorder of pregnancy and seems to be an early indicator of increased cardiovascular risk, but mechanisms underlying this association are unclear. In this study, we identified levels of circulating inflammatory markers and dynamic changes in the systemic acute-phase response in 44 women with a history of severe early-onset preeclampsia, compared with 29 controls with only uneventful pregnancies at 1.5 to 3.5 years postpartum. Models used were in vivo seasonal influenza vaccination and in vitro whole-blood culture with T-cell stimulants and the toll-like receptor-4 ligand lipopolysaccharide. Outcome measures were C-reactive protein, interleukin-6 (IL-6), IL-18, fibrinogen, myeloperoxidase, and a panel of 13 cytokines representative of the innate and adaptive inflammatory response, in addition to established cardiovascular markers. The in vivo acute-phase response was higher for women with previous preeclampsia than that for controls without such a history, although only significant for C-reactive protein (P=0.04). Preeclampsia was associated with higher IL-1β (P<0.05) and IL-8 (P<0.01) responses to T-cell activation. Hierarchical clustering revealed 2 distinct inflammatory clusters associated with previous preeclampsia: an adaptive response cluster associated with increased C-reactive protein and IL-6 before and after vaccination, increased weight, and low high-density lipoprotein cholesterol; and a toll-like receptor-4 mediated the cluster associated with increased IL-18 before and after vaccination but not associated with other cardiovascular markers. Furthermore, we found interactions between previous preeclampsia, common TLR4 gene variants, and the IL-18 response to vaccination. In conclusion, preeclampsia is associated with alterations in the inflammatory response postpartum mostly independent of other established cardiovascular risk markers. © 2015 American Heart Association, Inc.

Children's cortisol responses to a social evaluative laboratory stressor from early to middle childhood.

PubMed

Leppert, Katherine A; Kushner, Marissa; Smith, Victoria C; Lemay, Edward P; Dougherty, Lea R

2016-12-01

This study examined the stability of children's cortisol responses to a social evaluative laboratory stressor from early to middle childhood. Ninety-six children (51 males) completed stress-inducing laboratory tasks and provided five salivary cortisol samples in early (W1) and middle (W2) childhood. Although W1 cortisol responses did not predict W2 cortisol responses, children's cortisol responses demonstrated change: compared to their W1 cortisol responses, children's W2 cortisol responses demonstrated an increased slope and more negative quadratic curvature. Furthermore, child psychiatric symptoms at W1 moderated the stability of children's cortisol responses. Children with fewer preschool psychiatric symptoms demonstrated greater inter-individual and intra-individual stability, whereas children with higher preschool psychiatric symptoms and comorbidity demonstrated systematic inter-individual and intra-individual instability in cortisol responses over time. Findings suggest a developmental shift toward increasing cortisol stress responses from early to middle childhood and highlight preschool psychopathology as a moderator of stability in children's cortisol responses over time. © 2016 Wiley Periodicals, Inc.

Identification of diverse defense mechanisms in rainbow trout red blood cells in response to halted replication of VHS virus.

PubMed

Nombela, Ivan; Puente-Marin, Sara; Chico, Veronica; Villena, Alberto J; Carracedo, Begoña; Ciordia, Sergio; Mena, Maria Carmen; Mercado, Luis; Perez, Luis; Coll, Julio; Estepa, Amparo; Ortega-Villaizan, Maria Del Mar

2017-01-01

Background: It has been described that fish nucleated red blood cells (RBCs) generate a wide variety of immune-related gene transcripts when viruses highly replicate inside them and are their main target cell. The immune response and mechanisms of fish RBCs against viruses targeting other cells or tissues has not yet been explored and is the objective of our study. Methods: Rainbow trout RBCs were obtained from peripheral blood, ficoll purified and exposed to Viral Haemorrhagic Septicaemia virus (VHSV). Immune response was evaluated by means of RT-qPCR, flow cytometry, immunofluorescence and isobaric tag for relative and absolute quantification (iTRAQ) protein profiling. Results: VHSV N gene transcripts incremented early postexposure and were drastically decreased after 6 hours postexposure (hpe). The expression of type I interferon ( ifn1 ) gene was significantly downregulated at early postexposure (3 hpe), together with a gradual downregulation of interferon-inducible mx and pkr genes until 72 hpe. Type I IFN protein was downregulated and interferon-inducible Mx protein was maintained at basal levels. Co-culture assays of RBCs, previously exposed to UV-inactivated VHSV, and TSS (stromal cell line from spleen) revealed IFN crosstalk between both cell types. On the other hand, anti-microbial peptide β-defensin 1 and neutrophil chemotactic factor interleukin 8 were slightly upregulated in VHSV-exposed RBCs. iTRAQ profiling revealed that VHSV exposure can induce a global protein downregulation in rainbow trout RBCs, mainly related to RNA stability and proteasome pathways. Antioxidant/antiviral response is also suggested to be involved in the response of rainbow trout RBCs to VHSV. Conclusions: A variety of mechanisms are proposed to be implicated in the antiviral response of rainbow trout RBCs against VHSV halted infection. Ongoing research is focused on understanding the mechanisms in detail.

Identification of diverse defense mechanisms in rainbow trout red blood cells in response to halted replication of VHS virus

PubMed Central

Nombela, Ivan; Puente-Marin, Sara; Chico, Veronica; Villena, Alberto J.; Carracedo, Begoña; Ciordia, Sergio; Mena, Maria Carmen; Mercado, Luis; Perez, Luis; Coll, Julio; Ortega-Villaizan, Maria del Mar

2018-01-01

Background: It has been described that fish nucleated red blood cells (RBCs) generate a wide variety of immune-related gene transcripts when viruses highly replicate inside them and are their main target cell. The immune response and mechanisms of fish RBCs against viruses targeting other cells or tissues has not yet been explored and is the objective of our study. Methods: Rainbow trout RBCs were obtained from peripheral blood, ficoll purified and exposed to Viral Haemorrhagic Septicaemia virus (VHSV). Immune response was evaluated by means of RT-qPCR, flow cytometry, immunofluorescence and isobaric tag for relative and absolute quantification (iTRAQ) protein profiling. Results: VHSV N gene transcripts incremented early postexposure and were drastically decreased after 6 hours postexposure (hpe). The expression of type I interferon ( ifn1) gene was significantly downregulated at early postexposure (3 hpe), together with a gradual downregulation of interferon-inducible mx and pkr genes until 72 hpe. Type I IFN protein was downregulated and interferon-inducible Mx protein was maintained at basal levels. Co-culture assays of RBCs, previously exposed to UV-inactivated VHSV, and TSS (stromal cell line from spleen) revealed IFN crosstalk between both cell types. On the other hand, anti-microbial peptide β-defensin 1 and neutrophil chemotactic factor interleukin 8 were slightly upregulated in VHSV-exposed RBCs. iTRAQ profiling revealed that VHSV exposure can induce a global protein downregulation in rainbow trout RBCs, mainly related to RNA stability and proteasome pathways. Antioxidant/antiviral response is also suggested to be involved in the response of rainbow trout RBCs to VHSV. Conclusions: A variety of mechanisms are proposed to be implicated in the antiviral response of rainbow trout RBCs against VHSV halted infection. Ongoing research is focused on understanding the mechanisms in detail. PMID:29527292

Frameworks for Response to Intervention in Early Childhood: Description and Implications

ERIC Educational Resources Information Center

Communication Disorders Quarterly, 2014

2014-01-01

In February, 2013, the Division of Early Childhood, the National Association for the Education of Young Children, and the National Head Start Association released a collaborative paper to provide clarification and assistance regarding the relationship of response to intervention (RTI) with the field of early childhood (EC). In addition to…

Early improvements in anxiety, depression, and anger/hostility symptoms and response to antidepressant treatment.

PubMed

Farabaugh, Amy; Sonawalla, Shamsah; Johnson, Daniel P; Witte, Janet; Papakostas, George I; Goodness, Tracie; Clain, Alisabet; Baer, Lee; Mischoulon, David; Fava, Maurizio; Harley, Rebecca

2010-08-01

The purpose of this study was to examine whether treatment response to fluoxetine by depressed outpatients was predicted by early improvement on any of 3 subscales (Anxiety, Depression, and Anger/Hostility) of the Symptom Questionnaire (SQ). We evaluated 169 depressed outpatients (52.6% female) between ages 18 and 65 (mean age, 40.3 +/- 10.6 years) meeting DSM-IIIR criteria for major depressive disorder (MDD). All patients completed the SQ at baseline (week 0) and at weeks 2, 4, and 8 of treatment with fluoxetine 20 mg/d. We defined treatment response as a > or= 50% reduction in score on the 17-item Hamilton Rating Scale for Depression, and early improvement on 3 SQ subscales (Anxiety, Depression, and Anger/Hostility) as a >30% reduction in score by week 2. The percentage of patients with significant early improvement in anger was significantly greater than the percentage of those with early improvements in anxiety or depression. When early improvement on the Anxiety, Depression, and Anger/Hostility subscales of the SQ were assessed independently by logistic regression, all 3 subscales were predictors of response to treatment. Early improvement in anger, anxiety, and depressive symptoms may predict response to antidepressant treatment among outpatients with MDD.

Early Twentieth Century Responses to the Drug Problem.

ERIC Educational Resources Information Center

Pfennig, Dennis Joseph

1991-01-01

Describes early twentieth-century responses to the drug problem in the United States. Discusses pressure from the media and reformers to control the availability of drugs such as opium and cocaine that were widely available in over-the-counter medications. Focuses on New York State, which took the lead in enacting drug control legislation. (DK)

The early epigenetic response to ozone: impacts on DNA ...

EPA Pesticide Factsheets

Epigenetics have been increasingly recognized as a mechanism linking environment and gene expression. Despite awareness of the role of DNA methylation and hydroxymethylation as potential drivers of the response to air pollutants, very little work has been performed investigating the direct epigenetic effects following exposure to ambient air pollution. Thus the purpose of this study was to investigate the early epigenetic response to ozone in comparison to the epigenetic modifier 5-aza-2'-deoxycytidine (5-Aza) in rats. 12 week old, male Long-Evans rats (n=16) were exposed to 4 hours of whole-body 1.0 ppm ozone or air and immediately euthanized. A subset of animals were additionally treated with 5-Aza (n=16) to serve as an epigenetic control to ozone exposure. Neither 5-Aza nor ozone by itself induced changes to the global methylome or hydroxmethylome of the lung measured by ELISA. Despite this finding, ozone exposure induced a significant increase in the activity of the DNA methyltransferase enzymes in the lung which was reversed with 5-Aza treatment. Interestingly, a significant interaction between 5-Aza treatment and ozone exposure was found in a large array of data. The interaction between 5-Aza and ozone produced indicators of pulmonary edema and elevated lung damage. Along with these adverse changes, expression of major epigenetic enzymes (Tet 1-3, Dnmt3 a-b) were found to be perturbed in both the lung and hepatic tissues. While ozone exposure appears to in

Mechanical Response of DNA–Nanoparticle Crystals to Controlled Deformation

DOE PAGES

Lequieu, Joshua; Córdoba, Andrés; Hinckley, Daniel; ...

2016-08-17

The self-assembly of DNA-conjugated nanoparticles represents a promising avenue toward the design of engineered hierarchical materials. By using DNA to encode nanoscale interactions, macroscale crystals can be formed with mechanical properties that can, at least in principle, be tuned. Here we present in silico evidence that the mechanical response of these assemblies can indeed be controlled, and that subtle modifications of the linking DNA sequences can change the Young’s modulus from 97 kPa to 2.1 MPa. We rely on a detailed molecular model to quantify the energetics of DNA–nanoparticle assembly and demonstrate that the mechanical response is governed by entropic,more » rather than enthalpic, contributions and that the response of the entire network can be estimated from the elastic properties of an individual nanoparticle. The results here provide a first step toward the mechanical characterization of DNA–nanoparticle assemblies, and suggest the possibility of mechanical metamaterials constructed using DNA.« less

Mechanical Response of DNA–Nanoparticle Crystals to Controlled Deformation

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

Lequieu, Joshua; Córdoba, Andrés; Hinckley, Daniel

The self-assembly of DNA-conjugated nanoparticles represents a promising avenue toward the design of engineered hierarchical materials. By using DNA to encode nanoscale interactions, macroscale crystals can be formed with mechanical properties that can, at least in principle, be tuned. Here we present in silico evidence that the mechanical response of these assemblies can indeed be controlled, and that subtle modifications of the linking DNA sequences can change the Young’s modulus from 97 kPa to 2.1 MPa. We rely on a detailed molecular model to quantify the energetics of DNA–nanoparticle assembly and demonstrate that the mechanical response is governed by entropic,more » rather than enthalpic, contributions and that the response of the entire network can be estimated from the elastic properties of an individual nanoparticle. The results here provide a first step toward the mechanical characterization of DNA–nanoparticle assemblies, and suggest the possibility of mechanical metamaterials constructed using DNA.« less

Evidence-Based Early Reading Practices within a Response to Intervention System

ERIC Educational Resources Information Center

Bursuck, Bill; Blanks, Brooke

2010-01-01

Many students who experience reading failure are inappropriately placed in special education. A promising response to reducing reading failure and the overidentification of students for special education is Response to Intervention (RTI), a comprehensive early detection and prevention system that allows teachers to identify and support struggling…

Cortisol Response to Psychosocial Stress in Chinese Early Puberty Girls: Possible Role of Depressive Symptoms.

PubMed

Sun, Ying; Deng, Fang; Liu, Yang; Tao, Fang-Biao

2015-01-01

Objective. The present study aimed at investigating unique patterns of salivary cortisol reactivity and recovery in response to a social stressor among girls with early puberty and exploring possible role of depressive symptom in this association. Design. Case-control study. Patients. Fifty-six girls with early puberty and age- and body mass index- (BMI-) matched normal puberty controls (n = 56) were selected. Measurements. Salivary cortisol was measured in response to the Groningen Social Stress Test for Children. Results. Girls with early puberty had higher cortisol concentration at the end of the GSST (C3), cortisol concentration 20 min after the end of the GSST (C4), and AUC increment (AUCi) compared to non-early puberty girls. Depressive symptoms correlated with blunted HPA reactivity among girls with early puberty. Conclusion. This study demonstrated the disturbance effect of objectively examined early pubertal timing on HPA axis responses. It also suggested that stress reactivity might be blunted for individuals with depressive symptoms.

Neighborhood Deprivation during Early Childhood and Conduct Problems in Middle Childhood: Mediation by Aggressive Response Generation.

PubMed

Galán, Chardée A; Shaw, Daniel S; Dishion, Thomas J; Wilson, Melvin N

2017-07-01

The tremendous negative impact of conduct problems to the individual and society has provided the impetus for identifying risk factors, particularly in early childhood. Exposure to neighborhood deprivation in early childhood is a robust predictor of conduct problems in middle childhood. Efforts to identify and test mediating mechanisms by which neighborhood deprivation confers increased risk for behavioral problems have predominantly focused on peer relationships and community-level social processes. Less attention has been dedicated to potential cognitive mediators of this relationship, such as aggressive response generation, which refers to the tendency to generate aggressive solutions to ambiguous social stimuli with negative outcomes. In this study, we examined aggressive response generation, a salient component of social information processing, as a mediating process linking neighborhood deprivation to later conduct problems at age 10.5. Participants (N = 731; 50.5 % male) were drawn from a multisite randomized prevention trial that includes an ethnically diverse and low-income sample of male and female children and their primary caregivers followed prospectively from toddlerhood to middle childhood. Results indicated that aggressive response generation partially mediated the relationship between neighborhood deprivation and parent- and teacher-report of conduct problems, but not youth-report. Results suggest that the detrimental effects of neighborhood deprivation on youth adjustment may occur by altering the manner in which children process social information.

Neighborhood Deprivation during Early Childhood and Conduct Problems in Middle Childhood: Mediation by Aggressive Response Generation

PubMed Central

Shaw, Daniel S.; Dishion, Thomas J.; Wilson, Melvin N.

2018-01-01

The tremendous negative impact of conduct problems to the individual and society has provided the impetus for identifying risk factors, particularly in early childhood. Exposure to neighborhood deprivation in early childhood is a robust predictor of conduct problems in middle childhood. Efforts to identify and test mediating mechanisms by which neighborhood deprivation confers increased risk for behavioral problems have predominantly focused on peer relationships and community-level social processes. Less attention has been dedicated to potential cognitive mediators of this relationship, such as aggressive response generation, which refers to the tendency to generate aggressive solutions to ambiguous social stimuli with negative outcomes. In this study, we examined aggressive response generation, a salient component of social information processing, as a mediating process linking neighborhood deprivation to later conduct problems at age 10.5. Participants (N = 731; 50.5 % male) were drawn from a multisite randomized prevention trial that includes an ethnically diverse and low-income sample of male and female children and their primary caregivers followed prospectively from toddlerhood to middle childhood. Results indicated that aggressive response generation partially mediated the relationship between neighborhood deprivation and parent- and teacher-report of conduct problems, but not youth-report. Results suggest that the detrimental effects of neighborhood deprivation on youth adjustment may occur by altering the manner in which children process social information. PMID:27696324

Designing allostery-inspired response in mechanical networks

PubMed Central

Rocks, Jason W.; Pashine, Nidhi; Bischofberger, Irmgard; Goodrich, Carl P.; Liu, Andrea J.; Nagel, Sidney R.

2017-01-01

Recent advances in designing metamaterials have demonstrated that global mechanical properties of disordered spring networks can be tuned by selectively modifying only a small subset of bonds. Here, using a computationally efficient approach, we extend this idea to tune more general properties of networks. With nearly complete success, we are able to produce a strain between any two target nodes in a network in response to an applied source strain on any other pair of nodes by removing only ∼1% of the bonds. We are also able to control multiple pairs of target nodes, each with a different individual response, from a single source, and to tune multiple independent source/target responses simultaneously into a network. We have fabricated physical networks in macroscopic 2D and 3D systems that exhibit these responses. This work is inspired by the long-range coupled conformational changes that constitute allosteric function in proteins. The fact that allostery is a common means for regulation in biological molecules suggests that it is a relatively easy property to develop through evolution. In analogy, our results show that long-range coupled mechanical responses are similarly easy to achieve in disordered networks. PMID:28223534

Designing allostery-inspired response in mechanical networks.

PubMed

Rocks, Jason W; Pashine, Nidhi; Bischofberger, Irmgard; Goodrich, Carl P; Liu, Andrea J; Nagel, Sidney R

2017-03-07

Recent advances in designing metamaterials have demonstrated that global mechanical properties of disordered spring networks can be tuned by selectively modifying only a small subset of bonds. Here, using a computationally efficient approach, we extend this idea to tune more general properties of networks. With nearly complete success, we are able to produce a strain between any two target nodes in a network in response to an applied source strain on any other pair of nodes by removing only ∼1% of the bonds. We are also able to control multiple pairs of target nodes, each with a different individual response, from a single source, and to tune multiple independent source/target responses simultaneously into a network. We have fabricated physical networks in macroscopic 2D and 3D systems that exhibit these responses. This work is inspired by the long-range coupled conformational changes that constitute allosteric function in proteins. The fact that allostery is a common means for regulation in biological molecules suggests that it is a relatively easy property to develop through evolution. In analogy, our results show that long-range coupled mechanical responses are similarly easy to achieve in disordered networks.

Predictors of Responsiveness to Early Literacy Intervention: A 10-Year Update

ERIC Educational Resources Information Center

Lam, Elizabeth A.; McMaster, Kristen L.

2014-01-01

The purpose of this review was to update previous reviews on factors related to students' responsiveness to early literacy intervention. The 14 studies in this synthesis used experimental designs, provided small-group or one-on-one reading interventions, and analyzed factors related to responsiveness to those interventions. Participants were…

ATM-dependent E2F1 accumulation in the nucleolus is an indicator of ribosomal stress in early response to DNA damage

PubMed Central

Jin, Ya-Qiong; An, Guo-Shun; Ni, Ju-Hua; Li, Shu-Yan; Jia, Hong-Ti

2014-01-01

The nucleolus plays a major role in ribosome biogenesis. Most genotoxic agents disrupt nucleolar structure and function, which results in the stabilization/activation of p53, inducing cell cycle arrest or apoptosis. Likewise, transcription factor E2F1 as a DNA damage responsive protein also plays roles in cell cycle arrest, DNA repair, or apoptosis in response to DNA damage through transcriptional response and protein–protein interaction. Furthermore, E2F1 is known to be involved in regulating rRNA transcription. However, how E2F1 displays in coordinating DNA damage and nucleolar stress is unclear. In this study, we demonstrate that ATM-dependent E2F1 accumulation in the nucleolus is a characteristic feature of nucleolar stress in early response to DNA damage. We found that at the early stage of DNA damage, E2F1 accumulation in the nucleolus was an ATM-dependent and a common event in p53-suficient and -deficient cells. Increased nucleolar E2F1 was sequestered by the nucleolar protein p14ARF, which repressed E2F1-dependent rRNA transcription initiation, and was coupled with S phase. Our data indicate that early accumulation of E2F1 in the nucleolus is an indicator for nucleolar stress and a component of ATM pathway, which presumably buffers elevation of E2F1 in the nucleoplasm and coordinates the diversifying mechanisms of E2F1 acts in cell cycle progression and apoptosis in early response to DNA damage. PMID:24675884

ATM-dependent E2F1 accumulation in the nucleolus is an indicator of ribosomal stress in early response to DNA damage.

PubMed

Jin, Ya-Qiong; An, Guo-Shun; Ni, Ju-Hua; Li, Shu-Yan; Jia, Hong-Ti

2014-01-01

The nucleolus plays a major role in ribosome biogenesis. Most genotoxic agents disrupt nucleolar structure and function, which results in the stabilization/activation of p53, inducing cell cycle arrest or apoptosis. Likewise, transcription factor E2F1 as a DNA damage responsive protein also plays roles in cell cycle arrest, DNA repair, or apoptosis in response to DNA damage through transcriptional response and protein-protein interaction. Furthermore, E2F1 is known to be involved in regulating rRNA transcription. However, how E2F1 displays in coordinating DNA damage and nucleolar stress is unclear. In this study, we demonstrate that ATM-dependent E2F1 accumulation in the nucleolus is a characteristic feature of nucleolar stress in early response to DNA damage. We found that at the early stage of DNA damage, E2F1 accumulation in the nucleolus was an ATM-dependent and a common event in p53-suficient and -deficient cells. Increased nucleolar E2F1 was sequestered by the nucleolar protein p14ARF, which repressed E2F1-dependent rRNA transcription initiation, and was coupled with S phase. Our data indicate that early accumulation of E2F1 in the nucleolus is an indicator for nucleolar stress and a component of ATM pathway, which presumably buffers elevation of E2F1 in the nucleoplasm and coordinates the diversifying mechanisms of E2F1 acts in cell cycle progression and apoptosis in early response to DNA damage.

Cortisol Stress Response Variability in Early Adolescence Attachment, Affect and Sex

PubMed Central

Cameron, Catherine Ann; McKay, Stacey; Susman, Elizabeth J.; Wynne-Edwards, Katherine; Wright, Joan M.; Weinberg, Joanne

2017-01-01

Attachment, affect, and sex shape responsivity to psychosocial stress. Concurrent social contexts influence cortisol secretion, a stress hormone and biological marker of hypothalamic–pituitary–adrenal axis activity. Patterns of attachment, emotion status, and sex were hypothesized to relate to bifurcated, that is, accentuated and attenuated, cortisol reactivity. The theoretical framework for this study posits that multiple individual differences mediate a cortisol stress response. The effects of two psychosocial stress interventions, a modified Trier Social Stress Test for Teens and the Frustration Social Stressor for Adolescents were developed and investigated with early adolescents. Both of these protocols induced a significant stress reaction and evoked predicted bifurcation in cortisol responses; an increase or decrease from baseline to reactivity. In Study I, 120 predominantly middle-class, Euro-Canadian early adolescents with a mean age of 13.43 years were studied. The girls' attenuated cortisol reactivity to the public performance stressor related significantly to their self-reported lower maternal-attachment and higher trait-anger. In Study II, a community sample of 146 predominantly Euro-Canadian middle-class youth, with an average age of 14.5 years participated. Their self-reports of higher trait-anger and trait-anxiety, and lower parental attachment by both sexes related differentially to accentuated and attenuated cortisol reactivity to the frustration stressor. Thus, attachment, affect, sex, and the stressor contextual factors were associated with the adrenal-cortical responses of these adolescents through complex interactions. Further studies of individual differences in physiological responses to stress are called for in order to clarify the identities of concurrent protective and risk factors in the psychosocial stress and physiological stress responses of early adolescents. PMID:27468997

Cortisol Stress Response Variability in Early Adolescence: Attachment, Affect and Sex.

PubMed

Cameron, Catherine Ann; McKay, Stacey; Susman, Elizabeth J; Wynne-Edwards, Katherine; Wright, Joan M; Weinberg, Joanne

2017-01-01

Attachment, affect, and sex shape responsivity to psychosocial stress. Concurrent social contexts influence cortisol secretion, a stress hormone and biological marker of hypothalamic-pituitary-adrenal axis activity. Patterns of attachment, emotion status, and sex were hypothesized to relate to bifurcated, that is, accentuated and attenuated, cortisol reactivity. The theoretical framework for this study posits that multiple individual differences mediate a cortisol stress response. The effects of two psychosocial stress interventions, a modified Trier Social Stress Test for Teens and the Frustration Social Stressor for Adolescents were developed and investigated with early adolescents. Both of these protocols induced a significant stress reaction and evoked predicted bifurcation in cortisol responses; an increase or decrease from baseline to reactivity. In Study I, 120 predominantly middle-class, Euro-Canadian early adolescents with a mean age of 13.43 years were studied. The girls' attenuated cortisol reactivity to the public performance stressor related significantly to their self-reported lower maternal-attachment and higher trait-anger. In Study II, a community sample of 146 predominantly Euro-Canadian middle-class youth, with an average age of 14.5 years participated. Their self-reports of higher trait-anger and trait-anxiety, and lower parental attachment by both sexes related differentially to accentuated and attenuated cortisol reactivity to the frustration stressor. Thus, attachment, affect, sex, and the stressor contextual factors were associated with the adrenal-cortical responses of these adolescents through complex interactions. Further studies of individual differences in physiological responses to stress are called for in order to clarify the identities of concurrent protective and risk factors in the psychosocial stress and physiological stress responses of early adolescents.

Early Impairment of Lung Mechanics in a Murine Model of Marfan Syndrome

PubMed Central

Uriarte, Juan J.; Meirelles, Thayna; Gorbenko del Blanco, Darya; Nonaka, Paula N.; Campillo, Noelia; Sarri, Elisabet; Navajas, Daniel; Egea, Gustavo; Farré, Ramon

2016-01-01

Early morbidity and mortality in patients with Marfan syndrome (MFS) -a connective tissue disease caused by mutations in fibrillin-1 gene- are mainly caused by aorta aneurysm and rupture. However, the increase in the life expectancy of MFS patients recently achieved by reparatory surgery promotes clinical manifestations in other organs. Although some studies have reported respiratory alterations in MFS, our knowledge of how this connective tissue disease modifies lung mechanics is scarce. Hence, we assessed whether the stiffness of the whole lung and of its extracellular matrix (ECM) is affected in a well-characterized MFS mouse model (FBN1C1039G/+). The stiffness of the whole lung and of its ECM were measured by conventional mechanical ventilation and atomic force microscopy, respectively. We studied 5-week and 9-month old mice, whose ages are representative of early and late stages of the disease. At both ages, the lungs of MFS mice were significantly more compliant than in wild type (WT) mice. By contrast, no significant differences were found in local lung ECM stiffness. Moreover, histopathological lung evaluation showed a clear emphysematous-like pattern in MFS mice since alveolar space enlargement was significantly increased compared with WT mice. These data suggest that the mechanism explaining the increased lung compliance in MFS is not a direct consequence of reduced ECM stiffness, but an emphysema-like alteration in the 3D structural organization of the lung. Since lung alterations in MFS are almost fully manifested at an early age, it is suggested that respiratory monitoring could provide early biomarkers for diagnosis and/or follow-up of patients with the Marfan syndrome. PMID:27003297

Early stage response problem for post-disaster incidents

NASA Astrophysics Data System (ADS)

Kim, Sungwoo; Shin, Youngchul; Lee, Gyu M.; Moon, Ilkyeong

2018-07-01

Research on evacuation plans for reducing damages and casualties has been conducted to advise defenders against threats. However, despite the attention given to the research in the past, emergency response management, designed to neutralize hazards, has been undermined since planners frequently fail to apprehend the complexities and contexts of the emergency situation. Therefore, this study considers a response problem with unique characteristics for the duration of the emergency. An early stage response problem is identified to find the optimal routing and scheduling plan for responders to prevent further hazards. Due to the complexity of the proposed mathematical model, two algorithms are developed. Data from a high-rise building, called Central City in Seoul, Korea, are used to evaluate the algorithms. Results show that the proposed algorithms can procure near-optimal solutions within a reasonable time.

Mechanisms and pharmacogenetic signals underlying thiazide diuretics blood pressure response

PubMed Central

Shahin, Mohamed H; Johnson, Julie A

2016-01-01

Thiazide (TZD) diuretics are among the most commonly prescribed antihypertensives globally; however their chronic blood pressure (BP) lowering mechanism remains unclear. Herein we discuss the current evidence regarding specific mechanisms regulating the antihypertensive effects of TZDs, suggesting that TZDs act via multiple complex and interacting mechanisms, including natriuresis with short term use and direct vasodilatory effects chronically. Additionally, we review pharmacogenomics signals that have been associated with TZDs BP-response in several cohorts (i.e. NEDD4L, PRKCA, EDNRA-GNAS, and YEATS4) and discuss how these genes might be related to TZD BP-response mechanism. Understanding the association between these genes and TZD BP mechanism might facilitate the development of new drugs and therapeutic approaches based on a deeper understanding of the determinants of BP-response. PMID:26874237

Mechanisms and pharmacogenetic signals underlying thiazide diuretics blood pressure response.

PubMed

Shahin, Mohamed H; Johnson, Julie A

2016-04-01

Thiazide (TZD) diuretics are among the most commonly prescribed antihypertensives globally; however their chronic blood pressure (BP) lowering mechanism remains unclear. Herein we discuss the current evidence regarding specific mechanisms regulating the antihypertensive effects of TZDs, suggesting that TZDs act via multiple complex and interacting mechanisms, including natriuresis with short term use and direct vasodilatory effects chronically. Additionally, we review pharmacogenomics signals that have been associated with TZDs BP-response in several cohorts (i.e. NEDD4L, PRKCA, EDNRA-GNAS, and YEATS4) and discuss how these genes might be related to TZD BP-response mechanism. Understanding the association between these genes and TZD BP mechanism might facilitate the development of new drugs and therapeutic approaches based on a deeper understanding of the determinants of BP-response. Copyright © 2016. Published by Elsevier Ltd.

Impacts of triclosan exposure on zebrafish early-life stage: Toxicity and acclimation mechanisms.

PubMed

Falisse, Elodie; Voisin, Anne-Sophie; Silvestre, Frédéric

2017-08-01

Triclosan (TCS) is a broad spectrum antibacterial agent widely used in personal care products and present in most aquatic ecosystems. This study investigated the occurrence of triclosan acclimation and the biological mechanisms underlying the stress response triggered in early-life stage of zebrafish. Zebrafish eggs were first exposed to four different sublethal concentrations of TCS (2, 20, 50 and 100μg/L) for 7days following fertilization and subsequently exposed to a lethal concentration of TCS (1000μg/L). During the time-to-death exposure (TTD), mortality was continuously recorded to evaluate if increased resistance occurred. Overall, larvae exposed to 50μg/L of TCS demonstrated higher sensitivity, with delayed hatching and increased mortality during the sub-lethal exposure and significant lower mean time-to-death (TTD) value compared to the other groups. Interestingly, fish exposed to the highest concentration of TCS (100μg/L) presented a similar mean TTD value as controls and a significantly better survival in comparison with embryos exposed to 50μg/L, suggesting that acclimation process has been triggered at this concentration. Proteomic and enzymatic analyses were conducted on 7days post fertilization (dpf) larvae exposed to 50μg/L and 100μg/L of TCS giving insights into the functional changes triggered at those specific concentrations. TCS seemed to affect proteins involved in cytoskeleton, stress response, eyes and neuronal development. This was endorsed by the enzymatic results, which suggest impairment in glutathione metabolism and acute neurotoxicity. A significant 2.5-fold and 3-fold increase of AChE activity was observed following TCS exposure. Moreover, GPx activity was significantly increased whereas a significant inhibition of GR activity was observed, suggesting that de novo synthesis of reduced GSH might occur in order to maintain the ratio between reduced and oxidized GSH. Proteomic results revealed possible candidate protein involved in

Time matters - acute stress response and glucocorticoid sensitivity in early multiple sclerosis.

PubMed

Kern, Simone; Rohleder, Nicolas; Eisenhofer, Graeme; Lange, Jan; Ziemssen, Tjalf

2014-10-01

Psychosocial stress has frequently been associated with disease activity and acute exacerbations in multiple sclerosis (MS). Despite this well established finding, strikingly little is known about the acute hypothalamic-pituitary-adrenal (HPA) and sympathetic-adrenal-medullary (SAM) stress response in MS. Twenty-six early relapsing-remitting MS (RRMS) patients and seventeen age- and sex-matched healthy control subjects (CS) took part in the Trier Social Stress Test (TSST), a well validated psycho-social laboratory stress protocol. Repeated blood samples were analyzed for stress-related cortisol and catecholamine levels as well as for glucocorticoid sensitivity (GCS) of target immune cells. Chronic and acute stress appraisals were assessed by self-report measures. RRMS patients and CS did not differ in stress-related cortisol/catecholamine levels, GCS or stress appraisal in response to the TSST. However, cortisol release as well as GCS was strongly correlated with time since diagnosis but not with neurological disability. Patients with shorter disease duration (2-12 months) expressed a significantly higher cortisol stress response while MS patients with longer disease duration (14-36 months) showed a significantly diminished HPA response as well as lower post-stress GCS. There is evidence for a time-dependent variability in the HPA stress system with an increased cortisol stress response in the first year after diagnosis along with a more blunted HPA stress response and a diminished GCS in subsequent disease stages. Data underscore the highly dynamic nature of HPA axis regulation in the MS disease process, which could possibly relate to compensatory mechanisms within a cytokine-HPA axis feedback circuit model. Copyright © 2014 Elsevier Inc. All rights reserved.

Can early host responses to mycobacterial infection predict eventual disease outcomes?

PubMed

de Silva, Kumudika; Begg, Douglas J; Plain, Karren M; Purdie, Auriol C; Kawaji, Satoko; Dhand, Navneet K; Whittington, Richard J

2013-11-01

Diagnostic tests used for Johne's disease in sheep either have poor sensitivity and specificity or only detect disease in later stages of infection. Predicting which of the infected sheep are likely to become infectious later in life is currently not feasible and continues to be a major hindrance in disease control. We conducted this longitudinal study to investigate if a suite of diagnostic tests conducted in Mycobacterium avium subspecies paratuberculosis (MAP) exposed lambs at 4 months post infection can accurately predict their clinical status at 12 months post infection. We tracked cellular and humoral responses and quantity of MAP shedding for up to 12 months post challenge in 20 controls and 37 exposed sheep. Infection was defined at necropsy by tissue culture and disease spectrum by lesion type. Data were analysed using univariable and multivariable logistic regression models and a subset of variables from the earliest period post inoculation (4 months) was selected for predicting disease outcomes later on (12 months). Sensitivity and specificity of tests and their combinations in series and parallel were determined. Early elevation in faecal MAP DNA quantity and a lower interferon gamma (IFNγ) response were significantly associated with sheep becoming infectious as well as progressing to severe disease. Conversely, early low faecal MAP DNA and higher interleukin-10 responses were significantly associated with an exposed animal developing protective immunity. Combination of early elevated faecal MAP DNA or lower IFNγ response had the highest sensitivity (75%) and specificity (81%) for identifying sheep that would become infectious. Collectively, these results highlight the potential for combined test interpretation to aid in the early prediction of sheep susceptibility to MAP infection. Copyright © 2013 Elsevier B.V. All rights reserved.

Negative affective spillover from daily events predicts early response to cognitive therapy for depression.

PubMed

Cohen, Lawrence H; Gunthert, Kathleen C; Butler, Andrew C; Parrish, Brendt P; Wenze, Susan J; Beck, Judith S

2008-12-01

This study evaluated the predictive role of depressed outpatients' (N = 62) affective reactivity to daily stressors in their rates of improvement in cognitive therapy (CT). For 1 week before treatment, patients completed nightly electronic diaries that assessed daily stressors and negative affect (NA). The authors used multilevel modeling to compute each patient's within-day relationship between daily stressors and daily NA (within-day reactivity), as well as the relationship between daily stressors and next-day NA (next-day reactivity; affective spillover). In growth model analyses, the authors evaluated the predictive role of patients' NA reactivity in their early (Sessions 1-4) and late (Sessions 5-12) response to CT. Within-day NA reactivity did not predict early or late response to CT. However, next-day reactivity predicted early response to CT, such that patients who had greater NA spillover in response to negative events had a slower rate of symptom change during the first 4 sessions. Affective spillover did not influence later response to CT. The findings suggest that depressed patients who have difficulty bouncing back the next day from their NA reactions to a relative increase in daily negative events will respond less quickly to the early sessions of CT.

Early Antibody Response Contributes to the Virus Eradication and Clinical Recovery of H7N9 Influenza Infection.

PubMed

Liu, Xi; Yang, Zheng; Yuan, Jing; Liao, Jian; Duan, Lian; Wang, Wenfei; Zhang, Fuping; Chen, Xinchun; Zhou, Boping

2017-09-01

A new type of highly pathogenic avian influenza virus, H7N9, has been a great threat to public health since its 2013 outbreak. The humoral immune response plays a critical role in protection from the influenza virus, but its role and kinetics in H7N9-infected patients remain to be determined. In this study, we performed a retrospective investigation of the antibody response in plasma samples from 37 cases of hospitalized patients and analysed the relationship between the antibody response and the clinical outcomes. Our results showed that the HA7-binding antibody was generated earlier than the neutralizing antibody. Higher titer of HA7-binding antibody during the first 14 days after disease onset were associated with a shorter virus-positive continuation period, which is an important risk predictor ( P <0.05). Additionally, the titers of HA7-binding antibody were consistently and significantly lower in patients who died than those who recovered from the severe disease. Unexpectedly, no correlation between the titer of neutralizing antibody and the resulting clinical outcomes was found, suggesting that a neutralizing antibody-independent mechanism also contributed to virus control. In summary, our data suggests that an early antibody response against H7N9 influenza virus contributes to the eradication of the virus. A higher, early HA7-binding antibody response is associated with better clinical outcomes in H7N9 patients. © 2017 by the Association of Clinical Scientists, Inc.

Designing allostery-inspired response in mechanical networks

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

Rocks, Jason W.; Pashine, Nidhi; Bischofberger, Irmgard

Recent advances in designing metamaterials have demonstrated that global mechanical properties of disordered spring networks can be tuned by selectively modifying only a small subset of bonds. Here, using a computationally efficient approach, we extend this idea to tune more general properties of networks. With nearly complete success, we are then able to produce a strain between any two target nodes in a network in response to an applied source strain on any other pair of nodes by removing only ~1% of the bonds. We are also able to control multiple pairs of target nodes, each with a different individualmore » response, from a single source, and to tune multiple independent source/target responses simultaneously into a network. We have fabricated physical networks in macroscopic 2D and 3D systems that exhibit these responses. This work is inspired by the long-range coupled conformational changes that constitute allosteric function in proteins. The fact that allostery is a common means for regulation in biological molecules suggests that it is a relatively easy property to develop through evolution. In analogy, our results show that long-range coupled mechanical responses are similarly easy to achieve in disordered networks.« less

Designing allostery-inspired response in mechanical networks

DOE PAGES

Rocks, Jason W.; Pashine, Nidhi; Bischofberger, Irmgard; ...

2017-02-21

Recent advances in designing metamaterials have demonstrated that global mechanical properties of disordered spring networks can be tuned by selectively modifying only a small subset of bonds. Here, using a computationally efficient approach, we extend this idea to tune more general properties of networks. With nearly complete success, we are then able to produce a strain between any two target nodes in a network in response to an applied source strain on any other pair of nodes by removing only ~1% of the bonds. We are also able to control multiple pairs of target nodes, each with a different individualmore » response, from a single source, and to tune multiple independent source/target responses simultaneously into a network. We have fabricated physical networks in macroscopic 2D and 3D systems that exhibit these responses. This work is inspired by the long-range coupled conformational changes that constitute allosteric function in proteins. The fact that allostery is a common means for regulation in biological molecules suggests that it is a relatively easy property to develop through evolution. In analogy, our results show that long-range coupled mechanical responses are similarly easy to achieve in disordered networks.« less

Estrogenic Mechanisms and Cardiac Responses Following Early Life Exposure to Bisphenol A (BPA) and Its Metabolite 4-Methyl-2,4-bis( p-hydroxyphenyl)pent-1-ene (MBP) in Zebrafish.

PubMed

Moreman, John; Takesono, Aya; Trznadel, Maciej; Winter, Matthew J; Perry, Alexis; Wood, Mark E; Rogers, Nicola J; Kudoh, Tetsuhiro; Tyler, Charles R

2018-06-05

Environmental exposure to Bisphenol A (BPA) has been associated with a range of adverse health effects, including on the cardiovascular system in humans. Lack of agreement on its mechanism(s) of action likely stem from comparisons between in vivo and in vitro test systems and potential multiple effects pathways. In rodents, in vivo, metabolic activation of BPA produces 4-methyl-2,4-bis(4-hydroxyphenyl)pent-1-ene (MBP), which is reported to be up to 1000 times more potent as an estrogen than BPA. We investigated the estrogenic effects and estrogen receptor signaling pathway(s) of BPA and MBP following early life exposure using a transgenic, estrogen responsive (ERE-TG) zebrafish and a targeted morpholino approach to knockdown the three fish estrogen receptor (ER) subtypes. The functional consequences of BPA exposure on the cardiovascular system of zebrafish larvae were also examined. The heart atrioventricular valves and the bulbus arteriosus were primary target tissues for both BPA and MBP in the ERE-TG zebrafish, and MBP was approximately 1000-fold more potent than BPA as an estrogen in these tissues. Estrogen receptor knockdown with morpholinos indicated that the estrogenic responses in the heart for both BPA and MBP were mediated via an estrogen receptor 1 (esr1) dependent pathway. At the highest BPA concentration tested (2500 μg/L), alterations in the atrial:ventricular beat ratio indicated a functional impact on the heart of 5 days post fertilization (dpf) larvae, and there was also a significantly reduced heart rate in these larvae at 14 dpf. Our findings indicate that some of the reported adverse effects on heart function associated with BPA exposure (in mammals) may act through an estrogenic mechanism, but that fish are unlikely to be susceptible to adverse effects on heart development for environmentally relevant exposures.

Sclerostin's role in bone's adaptive response to mechanical loading.

PubMed

Galea, Gabriel L; Lanyon, Lance E; Price, Joanna S

2017-03-01

Mechanical loading is the primary functional determinant of bone mass and architecture, and osteocytes play a key role in translating mechanical signals into (re)modelling responses. Although the precise mechanisms remain unclear, Wnt signalling pathway components, and the anti-osteogenic canonical Wnt inhibitor Sost/sclerostin in particular, play an important role in regulating bone's adaptive response to loading. Increases in loading-engendered strains down-regulate osteocyte sclerostin expression, whereas reduced strains, as in disuse, are associated with increased sclerostin production and bone loss. However, while sclerostin up-regulation appears to be necessary for the loss of bone with disuse, the role of sclerostin in the osteogenic response to loading is more complex. While mice unable to down-regulate sclerostin do not gain bone with loading, Sost knockout mice have an enhanced osteogenic response to loading. The molecular mechanisms by which osteocytes sense and transduce loading-related stimuli into changes in sclerostin expression remain unclear but include several, potentially interlinked, signalling cascades involving periostin/integrin, prostaglandin, estrogen receptor, calcium/NO and Igf signalling. Deciphering the mechanisms by which changes in the mechanical environment regulate sclerostin production may lead to the development of therapeutic strategies that can reverse the skeletal structural deterioration characteristic of disuse and age-related osteoporosis and enhance bones' functional adaptation to loading. By enhancing the osteogenic potential of the context in which individual therapies such as sclerostin antibodies act it may become possible to both prevent and reverse the age-related skeletal structural deterioration characteristic of osteoporosis. Copyright © 2016 The Authors. Published by Elsevier Inc. All rights reserved.

Early cell lineage specification in a marsupial: a case for diverse mechanisms among mammals.

PubMed

Frankenberg, Stephen; Shaw, Geoff; Freyer, Claudia; Pask, Andrew J; Renfree, Marilyn B

2013-03-01

Early cell lineage specification in eutherian mammals results in the formation of a pluripotent inner cell mass (ICM) and trophoblast. By contrast, marsupials have no ICM. Here, we present the first molecular analysis of mechanisms of early cell lineage specification in a marsupial, the tammar wallaby. There was no overt differential localisation of key lineage-specific transcription factors in cleavage and early unilaminar blastocyst stages. Pluriblast cells (equivalent to the ICM) became distinguishable from trophoblast cells by differential expression of POU5F1 and, to a greater extent, POU2, a paralogue of POU5F1. Unlike in the mouse, pluriblast-trophoblast differentiation coincided with a global nuclear-to-cytoplasmic transition of CDX2 localisation. Also unlike in the mouse, Hippo pathway factors YAP and WWTR1 showed mutually distinct localisation patterns that suggest non-redundant roles. NANOG and GATA6 were conserved as markers of epiblast and hypoblast, respectively, but some differences to the mouse were found in their mode of differentiation. Our results suggest that there is considerable evolutionary plasticity in the mechanisms regulating early lineage specification in mammals.

Mechanical response of 3D Insert® PCL to compression.

PubMed

Brunelli, M; Perrault, C M; Lacroix, D

2017-01-01

3D polymeric scaffolds are increasingly used for in vitro experiments aiming to mimic the environment found in vivo, to support for cellular growth and to induce differentiation through the application of external mechanical cues. In research, experimental results must be shown to be reproducible to be claimed as valid and the first clause to ensure consistency is to provide identical initial experimental conditions between trials. As a matter of fact, 3D structures fabricated in batch are supposed to present a highly reproducible geometry and consequently, to give the same bulk response to mechanical forces. This study aims to measure the overall mechanical response to compression of commercially available 3D Insert PCL scaffolds (3D PCL) fabricated in series by fuse deposition and evaluate how small changes in the architecture of scaffolds affect the mechanical response. The apparent elastic modulus (Ea) was evaluated by performing quasi-static mechanical tests at various temperatures showing a decrease in material stiffness from 5MPa at 25°C to 2.2MPa at 37°C. Then, a variability analysis revealed variations in Ea related to the repositioning of the sample into the testing machine, but also consistent differences comparing different scaffolds. To clarify the source of the differences measured in the mechanical response, the same scaffolds previously undergoing compression, were scanned by micro computed tomography (μCT) to identify any architectural difference. Eventually, to clarify the contribution given by differences in the architecture to the standard deviation of Ea, their mechanical response was qualitatively compared to a compact reference material such as polydimethylsiloxane (PDMS). This study links the geometry, architecture and mechanical response to compression of 3D PCL scaffolds and shows the importance of controlling such parameters in the manufacturing process to obtain scaffolds that can be used in vitro or in vivo under reproducible

Plasma-Sprayed Titanium Patterns for Enhancing Early Cell Responses

NASA Astrophysics Data System (ADS)

Shi, Yunqi; Xie, Youtao; Pan, Houhua; Zheng, Xuebin; Huang, Liping; Ji, Fang; Li, Kai

2016-06-01

Titanium coating has been widely used as a biocompatible metal in biomedical applications. However, the early cell responses and long-term fixation of titanium implants are not satisfied. To obviate these defects, in this paper, micro-post arrays with various widths (150-1000 μm) and intervals (100-300 μm) were fabricated on the titanium substrate by template-assisted plasma spraying technology. In vitro cell culture experiments showed that MC3T3-E1 cells exhibited significantly higher osteogenic differentiation as well as slightly improved adhesion and proliferation on the micro-patterned coatings compared with the traditional one. The cell number on the pattern with 1000 µm width reached 130% after 6 days of incubation, and the expressions of osteopontin (OPN) as well as osteocalcin (OC) were doubled. No obvious difference was found in cell adhesion on various size patterns. The present micro-patterned coatings proposed a new modification method for the traditional plasma spraying technology to enhance the early cell responses and convenience for the bone in-growth.

Hydro-mechanical mechanism and thresholds of rainfall-induced unsaturated landslides

NASA Astrophysics Data System (ADS)

Yang, Zongji; Lei, Xiaoqin; Huang, Dong; Qiao, Jianping

2017-04-01

The devastating Ms 8 Wenchuan earthquake in 2008 created the greatest number of co-seismic mountain hazards ever recorded in China. However, the dynamics of rainfall induced mass remobilization and transport deposits after giant earthquake are not fully understood. Moreover, rainfall intensity and duration (I-D) methods are the predominant early warning indicators of rainfall-induced landslides in post-earthquake region, which are a convenient and straight-forward way to predict the hazards. However, the rainfall-based criteria and thresholds are generally empirical and based on statistical analysis,consequently, they ignore the failure mechanisms of the landslides. This study examines the mechanism and hydro-mechanical behavior and thresholds of these unsaturated deposits under the influence of rainfall. To accomplish this, in situ experiments were performed in an instrumented landslide deposit, The field experimental tests were conducted on a natural co-seismic fractured slope to 1) simulate rainfall-induced shallow failures in the depression channels of a debris flow catchment in an earthquake-affected region, 2)explore the mechanisms and transient processes associated with hydro-mechanical parameter variations in response to the infiltration of rainfall, and 3) identify the hydrologic parameter thresholds and critical criteria of gravitational erosion in areas prone to mass remobilization as a source of debris flows. These experiments provided instrumental evidence and directly proved that post-earthquake rainfall-induced mass remobilization occurred under unsaturated conditions in response to transient rainfall infiltration, and revealed the presence of transient processes and the dominance of preferential flow paths during rainfall infiltration. A hydro-mechanical method was adopted for the transient hydrologic process modelling and unsaturated slope stability analysis. and the slope failures during the experimental test were reproduced by the model

Early and long term anamnestic response to HBV booster dose among fully vaccinated Egyptian children during infancy.

PubMed

Salama, Iman I; Sami, Samia M; Said, Zeinab N; Salama, Somaia I; Rabah, Thanaa M; Abdel-Latif, Ghada A; Elmosalami, Dalia M; Saleh, Rehan M; Abdel Mohsin, Aida M; Metwally, Ammal M; Hassanin, Amal I; Emam, Hanaa M; Hemida, Samia A; Elserougy, Safaa M; Shaaban, Fatma A; Fouad, Walaa A; Mohsen, Amira; El-Sayed, Manal H

2018-04-05

To evaluate early and long term anamnestic response to a booster dose of HBV vaccine among non-seroprotected children. A national community based project was carried out on 3600 children aged 9 months to 16 years, fully vaccinated during infancy. They were recruited from 6 governorates representing Egypt. It revealed that 1535 children (42.8%) had non sero-protective anti-HBs (<10 IU/L) and were HBsAg or anti-HBc negative. A challenging dose of 10 μg of mono-valent Euvax HBV vaccine was given to 1121/1535 children. Quantitative assessment of anti-HBs was performed to detect early (2-4 weeks) and long term (one year) anamnestic responses. Early anamnestic response developed among 967/1070 children (90.3%).Children having detectable anti-HBs (1-9 IU/L) significantly developed early anamnestic response (90%) compared to 85% with undetectable anti-HBs (<1 IU/L), P < 0.001. Multiple logistic analysis revealed that undetectable anti-HBs, living in rural residence and children aged 15-16 years were the most significant predicting risk factors for the absence of early anamnestic response (<10 IU/L), with AOR 2.7, 2.7 & 4.7 respectively. After one year, long term anamnestic response was absent among 15% of children who previously showed early response. Poor early anamnestic response and undetectable pre-booster anti-HBs were the significant predicting risk factors for absent long term anamnestic response, with AOR 18.7 & 2.7 respectively. Immunological memory for HBV vaccine outlasts the presence of anti- HBs and HBV vaccination program provides effective long term protection even in children showing waning or undetectable concentrations of anti-HBs. This signifies no need for a booster dose especially to healthy children. Copyright © 2018 Elsevier Ltd. All rights reserved.

Mechanisms Underlying Latent Disease Risk Associated with Early-Life Arsenic Exposure: Current Research Trends and Scientific Gaps

PubMed Central

Bailey, Kathryn A.; Smith, Allan H.; Tokar, Erik J.; Graziano, Joseph H.; Kim, Kyoung-Woong; Navasumrit, Panida; Ruchirawat, Mathuros; Thiantanawat, Apinya; Suk, William A.; Fry, Rebecca C.

2015-01-01

Background Millions of individuals worldwide, particularly those living in rural and developing areas, are exposed to harmful levels of inorganic arsenic (iAs) in their drinking water. Inorganic As exposure during key developmental periods is associated with a variety of adverse health effects, including those that are evident in adulthood. There is considerable interest in identifying the molecular mechanisms that relate early-life iAs exposure to the development of these latent diseases, particularly in relationship to cancer. Objectives This work summarizes research on the molecular mechanisms that underlie the increased risk of cancer development in adulthood that is associated with early-life iAs exposure. Discussion Epigenetic reprogramming that imparts functional changes in gene expression, the development of cancer stem cells, and immunomodulation are plausible underlying mechanisms by which early-life iAs exposure elicits latent carcinogenic effects. Conclusions Evidence is mounting that relates early-life iAs exposure and cancer development later in life. Future research should include animal studies that address mechanistic hypotheses and studies of human populations that integrate early-life exposure, molecular alterations, and latent disease outcomes. Citation Bailey KA, Smith AH, Tokar EJ, Graziano JH, Kim KW, Navasumrit P, Ruchirawat M, Thiantanawat A, Suk WA, Fry RC. 2016. Mechanisms underlying latent disease risk associated with early-life arsenic exposure: current research trends and scientific gaps. Environ Health Perspect 124:170–175; http://dx.doi.org/10.1289/ehp.1409360 PMID:26115410

Ekman pumping mechanism driving precipitation anomalies in response to equatorial heating

NASA Astrophysics Data System (ADS)

Hamouda, Mostafa E.; Kucharski, Fred

2018-03-01

In this paper some basic mechanisms for rainfall teleconnections to a localized tropical sea surface temperature anomaly are re-visited using idealized AGCM aqua-planet simulations. The dynamical response is generally in good agreement with the Gill-Matsuno theory. The mechanisms analyzed are (1) the stabilization of the tropical troposphere outside the heating region, (2) the Walker circulation modification and (3) Ekman pumping induced by the low-level circulation responses. It is demonstrated that all three mechanisms, and in particular (2) and (3), contribute to the remote rainfall teleconnections. However, mechanism (3) best coincides with the overall horizontal structure of rainfall responses. It is shown by using the models boundary layer parameterization that low-level vertical velocities are indeed caused by Ekman pumping and that this induces vertical velocities in the whole tropospheric column through convective feedbacks. Also the modification of the responses due to the presence of idealized warm pools is investigated. It is shown that warm pools modify the speed of the tropical waves, consistent with Doppler shifts and are thus able to modify the Walker circulation adjustments and remote rainfall responses. The sensitivity of the responses, and in particular the importance of the Ekman pumping mechanism, to large variations in the drag coefficient is also tested, and it is shown that the Ekman pumping mechanism is robust for a wide range of values.

Serum Response Factor (SRF) Ablation Interferes with Acute Stress-Associated Immediate and Long-Term Coping Mechanisms.

PubMed

Zimprich, Annemarie; Mroz, Gabi; Meyer Zu Reckendorf, Christopher; Anastasiadou, Sofia; Förstner, Philip; Garrett, Lillian; Hölter, Sabine M; Becker, Lore; Rozman, Jan; Prehn, Cornelia; Rathkolb, Birgit; Moreth, Kristin; Wurst, Wolfgang; Klopstock, Thomas; Klingenspor, Martin; Adamski, Jerzy; Wolf, Eckhard; Bekeredjian, Raffi; Fuchs, Helmut; Gailus-Durner, Valerie; de Angelis, Martin Hrabe; Knöll, Bernd

2017-12-01

Stress experience modulates behavior, metabolism, and energy expenditure of organisms. One molecular hallmark of an acute stress response is a rapid induction of immediate early genes (IEGs) such as c-Fos and Egr family members. IEG transcription in neurons is mediated by the neuronal activity-driven gene regulator serum response factor (SRF). We show a first role of SRF in immediate and long-lasting acute restraint stress (AS) responses. For this, we employed a standardized mouse phenotyping protocol at the German Mouse Clinic (GMC) including behavioral, metabolic, and cardiologic tests as well as gene expression profiling to analyze the consequences of forebrain-specific SRF deletion in mice exposed to AS. Adult mice with an SRF deletion in glutamatergic neurons (Srf; CaMKIIa-CreERT2 ) showed hyperactivity, decreased anxiety, and impaired working memory. In response to restraint AS, instant stress reactivity including locomotor behavior and corticosterone induction was impaired in Srf mutant mice. Interestingly, even several weeks after previous AS exposure, SRF-deficient mice showed long-lasting AS-associated changes including altered locomotion, metabolism, energy expenditure, and cardiovascular changes. This suggests a requirement of SRF for mediating long-term stress coping mechanisms in wild-type mice. SRF ablation decreased AS-mediated IEG induction and activity of the actin severing protein cofilin. In summary, our data suggest an SRF function in immediate AS reactions and long-term post-stress-associated coping mechanisms.

21 CFR 882.1880 - Evoked response mechanical stimulator.

Code of Federal Regulations, 2011 CFR

2011-04-01

... 21 Food and Drugs 8 2011-04-01 2011-04-01 false Evoked response mechanical stimulator. 882.1880 Section 882.1880 Food and Drugs FOOD AND DRUG ADMINISTRATION, DEPARTMENT OF HEALTH AND HUMAN SERVICES (CONTINUED) MEDICAL DEVICES NEUROLOGICAL DEVICES Neurological Diagnostic Devices § 882.1880 Evoked response...

The Reasons behind Early Adolescents' Responses to Peer Victimization

ERIC Educational Resources Information Center

Bellmore, Amy; Chen, Wei-Ting; Rischall, Emily

2013-01-01

Victims of school-based peer harassment face a range of risks including psycho-social, physical, and academic harm. The aim of the present study was to examine the behavioral coping responses used by early adolescents when they face peer victimization. To meet this aim, 216 sixth grade students (55% girls) from two urban middle schools and 254…

A Framework for Providing Culturally Responsive Early Intervention Services

ERIC Educational Resources Information Center

Bradshaw, Wendy

2013-01-01

The purpose of this article is to provide a framework that offers a way for early intervention (EI) service providers to better meet the needs of the culturally diverse children and families they serve. This framework was created to organize existing research and literature on cultural responsiveness in a way that fit the unique context of EI. The…

Cell response to long term mechanical interaction with nanopipettes

NASA Astrophysics Data System (ADS)

Orynbayeva, Zulfiya; Singhal, Riju; Vitol, Elina; Bouchard, Michael; Azizkhan-Clifford, Jane; Layton, Bradley; Friedman, Gary; Gogotsi, Yury

2009-03-01

Traditional microinjection into cells is performed over a relatively short term. Pipettes are typically withdrawn following any kind of injection. On the other hand, there is growing interest in using nanopipettes for cellular and subcellular probing. This interest is partly due to new developments in nanopipette technology which employ carbon nanotubes and provide robustness, flexibility, and biocompatibility. However, as far as we know, no systematic study of physiological, biochemical, and biophysical processes associated with cell response to lengthy mechanical stimulations by nanopipette probing have been performed so far. We present a detailed investigation of a wide range of effects of long term pipette insertion into a cell. Both traditional glass micropipettes and the novel carbon nanotube-tipped probes were involved in this study. The mechanism of Ca2+ response to the mechanical stimuli introduced by the nanopipette, and the role of different organelles in this mechanism were studied. We hypothesize that the calcium response is a function of cytoskeleton integrity and the mode of coupling between the cytoskeleton and the plasma membrane domains.

Thermo-mechanical response predictions for metal matrix composite laminates

NASA Technical Reports Server (NTRS)

Aboudi, J.; Hidde, J. S.; Herakovich, C. T.

1991-01-01

An analytical micromechanical model is employed for prediction of the stress-strain response of metal matrix composite laminates subjected to thermomechanical loading. The predicted behavior of laminates is based upon knowledge of the thermomechanical response of the transversely isotropic, elastic fibers and the elastic-viscoplastic, work-hardening matrix. The method is applied to study the behavior of silicon carbide/titanium metal matrix composite laminates. The response of laminates is compared with that of unidirectional lamina. The results demonstrate the effect of cooling from a stress-free temperature and the mismatch of thermal and mechanical properties of the constituent phases on the laminate's subsequent mechanical response. Typical results are presented for a variety of laminates subjected to monotonic tension, monotonic shear and cyclic tensile/compressive loadings.

Artificial Neural Network-Based Early-Age Concrete Strength Monitoring Using Dynamic Response Signals.

PubMed

Kim, Junkyeong; Lee, Chaggil; Park, Seunghee

2017-06-07

Concrete is one of the most common materials used to construct a variety of civil infrastructures. However, since concrete might be susceptible to brittle fracture, it is essential to confirm the strength of concrete at the early-age stage of the curing process to prevent unexpected collapse. To address this issue, this study proposes a novel method to estimate the early-age strength of concrete, by integrating an artificial neural network algorithm with a dynamic response measurement of the concrete material. The dynamic response signals of the concrete, including both electromechanical impedances and guided ultrasonic waves, are obtained from an embedded piezoelectric sensor module. The cross-correlation coefficient of the electromechanical impedance signals and the amplitude of the guided ultrasonic wave signals are selected to quantify the variation in dynamic responses according to the strength of the concrete. Furthermore, an artificial neural network algorithm is used to verify a relationship between the variation in dynamic response signals and concrete strength. The results of an experimental study confirm that the proposed approach can be effectively applied to estimate the strength of concrete material from the early-age stage of the curing process.

Artificial Neural Network-Based Early-Age Concrete Strength Monitoring Using Dynamic Response Signals

PubMed Central

Kim, Junkyeong; Lee, Chaggil; Park, Seunghee

2017-01-01

Concrete is one of the most common materials used to construct a variety of civil infrastructures. However, since concrete might be susceptible to brittle fracture, it is essential to confirm the strength of concrete at the early-age stage of the curing process to prevent unexpected collapse. To address this issue, this study proposes a novel method to estimate the early-age strength of concrete, by integrating an artificial neural network algorithm with a dynamic response measurement of the concrete material. The dynamic response signals of the concrete, including both electromechanical impedances and guided ultrasonic waves, are obtained from an embedded piezoelectric sensor module. The cross-correlation coefficient of the electromechanical impedance signals and the amplitude of the guided ultrasonic wave signals are selected to quantify the variation in dynamic responses according to the strength of the concrete. Furthermore, an artificial neural network algorithm is used to verify a relationship between the variation in dynamic response signals and concrete strength. The results of an experimental study confirm that the proposed approach can be effectively applied to estimate the strength of concrete material from the early-age stage of the curing process. PMID:28590456

Item response theory analysis of the mechanics baseline test

NASA Astrophysics Data System (ADS)

Cardamone, Caroline N.; Abbott, Jonathan E.; Rayyan, Saif; Seaton, Daniel T.; Pawl, Andrew; Pritchard, David E.

2012-02-01

Item response theory is useful in both the development and evaluation of assessments and in computing standardized measures of student performance. In item response theory, individual parameters (difficulty, discrimination) for each item or question are fit by item response models. These parameters provide a means for evaluating a test and offer a better measure of student skill than a raw test score, because each skill calculation considers not only the number of questions answered correctly, but the individual properties of all questions answered. Here, we present the results from an analysis of the Mechanics Baseline Test given at MIT during 2005-2010. Using the item parameters, we identify questions on the Mechanics Baseline Test that are not effective in discriminating between MIT students of different abilities. We show that a limited subset of the highest quality questions on the Mechanics Baseline Test returns accurate measures of student skill. We compare student skills as determined by item response theory to the more traditional measurement of the raw score and show that a comparable measure of learning gain can be computed.

Early laparotomy wound failure as the mechanism for incisional hernia formation

PubMed Central

Xing, Liyu; Culbertson, Eric J.; Wen, Yuan; Franz, Michael G.

2015-01-01

Background Incisional hernia is the most common complication of abdominal surgery leading to reoperation. In the United States, 200,000 incisional hernia repairs are performed annually, often with significant morbidity. Obesity is increasing the risk of laparotomy wound failure. Methods We used a validated animal model of incisional hernia formation. We intentionally induced laparotomy wound failure in otherwise normal adult, male Sprague-Dawley rats. Radio-opaque, metal surgical clips served as markers for the use of x-ray images to follow the progress of laparotomy wound failure. We confirmed radiographic findings of the time course for mechanical laparotomy wound failure by necropsy. Results Noninvasive radiographic imaging predicts early laparotomy wound failure and incisional hernia formation. We confirmed both transverse and craniocaudad migration of radio-opaque markers at necropsy after 28 d that was uniformly associated with the clinical development of incisional hernias. Conclusions Early laparotomy wound failure is a primary mechanism for incisional hernia formation. A noninvasive radiographic method for studying laparotomy wound healing may help design clinical trials to prevent and treat this common general surgical complication. PMID:23036516

A simple polymeric model describes cell nuclear mechanical response

NASA Astrophysics Data System (ADS)

Banigan, Edward; Stephens, Andrew; Marko, John

The cell nucleus must continually resist inter- and intracellular mechanical forces, and proper mechanical response is essential to basic cell biological functions as diverse as migration, differentiation, and gene regulation. Experiments probing nuclear mechanics reveal that the nucleus stiffens under strain, leading to two characteristic regimes of force response. This behavior depends sensitively on the intermediate filament protein lamin A, which comprises the outer layer of the nucleus, and the properties of the chromatin interior. To understand these mechanics, we study a simulation model of a polymeric shell encapsulating a semiflexible polymer. This minimalistic model qualitatively captures the typical experimental nuclear force-extension relation and observed nuclear morphologies. Using a Flory-like theory, we explain the simulation results and mathematically estimate the force-extension relation. The model and experiments suggest that chromatin organization is a dominant contributor to nuclear mechanics, while the lamina protects cell nuclei from large deformations.

Consequences of an Early PSA Response to Enzalutamide Treatment for Japanese Patients with Metastatic Castration-resistant Prostate Cancer.

PubMed

Kato, Haruo; Furuya, Yosuke; Miyazawa, Yoshiyuki; Miyao, Takeshi; Syuto, Takahiro; Nomura, Masashi; Sekine, Yoshitaka; Koike, Hidekazu; Matsui, Hiroshi; Shibata, Yasuhiro; Ito, Kazuto; Suzuki, Kazuhiro

2016-11-01

Recent studies have shown that an early prostate-specific antigen (PSA) response to androgen receptor (AR)-targeting agents in metastatic castration-resistant prostate cancer (mCRPC) is associated with a better prognosis. We analyzed early PSA response to enzalutamide and oncological outcomes to study their prognostic significance in the Japanese population. Fifty-one patients with mCRPC (26 of pre-docetaxel and 25 of post-docetaxel status) were treated with enzalutamide. The PSA progression-free survival (PFS), radiographic PFS (rPFS) and overall survival (OS) were assessed. The association of rPFS and OS in patients with an early PSA response at 4 weeks after commencement of enzalutamide was studied. Early PSA responses were significantly associated with a longer rPFS (median of 47.9 vs. 20.1 weeks, p<0.001, in patients exhibiting a 50% PSA response; median of 40.9 vs. 20.1 weeks, p=0.016, in patients exhibiting a 30% PSA response). OS was also significantly associated with an early PSA response (p=0.002 for patients exhibiting a 50% PSA response, p=0.003 for patients exhibiting a 30% PSA response). Multivariate analysis showed that the predictors of a 50% PSA response were an interval to mCRPC and a docetaxel treatment history, while the predictor of a 30% PSA response was a docetaxel treatment history. Furthermore, a 50% PSA response was independently prognostic of rPFS. An early PSA response to enzalutamide was significantly associated with a longer rPFS and OS. This information will aid in the management of patients treated with enzalutamide. Copyright© 2016 International Institute of Anticancer Research (Dr. John G. Delinassios), All rights reserved.

Mechanisms for creating accommodation space during early Tertiary sedimentation in Tibet.

NASA Astrophysics Data System (ADS)

Studnicki-Gizbert, C.; Burchfiel, B. C.

2003-12-01

The Tibetan plateau is for the most part underlain by rocks of pre-Cenozoic age, a fact that has hindered the identification of Cenozoic shortening structures that can be unequivocally related to the effects of India-Asia collision. Notably, however, the Qiangtang block contains a number of small, short wavelength basins filled with terrestrial sediments of early Tertiary age. Where these basins have been well studied, sedimentation is recognized as having occurred coevally with compressional deformation. The classic treatment of compressional basins appeals to accommodation space created by the flexure of an elastic plate in response to loads created by adjacent thrust fault bound ranges. It is unlikely that the Tertiary basins of the Qiangtang block formed in this manner. The wavelength of a classically modelled flexural basin is a basically a function of the thickness of the elastic plate and the density difference between sedimentary fill and ductile material underlying the plate. Assuming a model of elastic flexure, the very small wavelengths (5 - 30km) characteristic of Qiangtang basins would then imply extremely thin (~ 1-5 km) effective elastic plate thicknesses. These very low values are difficult to reconcile with any reasonable characterization of crustal rheology. Instead, these relatively small basins likely record the creation of accommodation space created by differential uplift across the strike of folds and faults. Stratal geometries and sedimentation rates reflect the kinematics and geometries of local compressional structures and the mechanical basis for the creation of accommodation space remains uncertain. Finally, the origin of these basins makes it unlikely that early Tertiary sedimentation represents a significant fraction of the upper crust of Tibetan plateau.

Enhancing early child care quality and learning for toddlers at risk: the responsive early childhood program.

PubMed

Landry, Susan H; Zucker, Tricia A; Taylor, Heather B; Swank, Paul R; Williams, Jeffrey M; Assel, Michael; Crawford, April; Huang, Weihua; Clancy-Menchetti, Jeanine; Lonigan, Christopher J; Phillips, Beth M; Eisenberg, Nancy; Spinrad, Tracy L; de Villiers, Jill; de Villiers, Peter; Barnes, Marcia; Starkey, Prentice; Klein, Alice

2014-02-01

Despite reports of positive effects of high-quality child care, few experimental studies have examined the process of improving low-quality center-based care for toddler-age children. In this article, we report intervention effects on child care teachers' behaviors and children's social, emotional, behavioral, early literacy, language, and math outcomes as well as the teacher-child relationship. The intervention targeted the use of a set of responsive teacher practices, derived from attachment and sociocultural theories, and a comprehensive curriculum. Sixty-five childcare classrooms serving low-income 2- and 3-year-old children were randomized into 3 conditions: business-as-usual control, Responsive Early Childhood Curriculum (RECC), and RECC plus explicit social-emotional classroom activities (RECC+). Classroom observations showed greater gains for RECC and RECC+ teachers' responsive practices including helping children manage their behavior, establishing a predictable schedule, and use of cognitively stimulating activities (e.g., shared book reading) compared with controls; however, teacher behaviors did not differ for focal areas such as sensitivity and positive discipline supports. Child assessments demonstrated that children in the interventions outperformed controls in areas of social and emotional development, although children's performance in control and intervention groups was similar for cognitive skills (language, literacy, and math). Results support the positive impact of responsive teachers and environments providing appropriate support for toddlers' social and emotional development. Possible explanations for the absence of systematic differences in children's cognitive skills are considered, including implications for practice and future research targeting low-income toddlers.

Developmental trajectory from early responses to transgressions to future antisocial behavior: Evidence for the role of the parent-child relationship from two longitudinal studies

PubMed Central

Kim, Sanghag; Kochanska, Grazyna; Boldt, Lea J.; Nordling, Jamie Koenig; O’Bleness, Jessica J.

2014-01-01

Parent-child relationships are critical in development, but much remains to be learned about mechanisms of their impact. We examined early parent-child relationship as a moderator of the developmental trajectory from children’s affective and behavioral responses to transgressions to future antisocial, externalizing behavior problems in Family Study (102 community mothers, fathers, and infants, followed through age 8) and Play Study (186 low-income, diverse mothers and toddlers, followed for 10 months). The relationship quality was indexed by attachment security in Family Study and maternal responsiveness in Play Study. Responses to transgressions (tense discomfort and reparation) were observed in laboratory mishaps that led children to believe they had damaged a valued object. Antisocial outcomes were rated by parents. In both studies, early relationship moderated the future developmental trajectory: Children’s attenuated tense discomfort predicted more antisocial outcomes, but only in insecure or unresponsive relationships. That risk was defused in secure or responsive relationships. Moderated mediation analyses in Family Study indicated that the links between low tense discomfort and future antisocial behavior in insecure parent-child dyads were mediated by parental stronger discipline pressure. By influencing indirectly future developmental sequelae, early relationship may increase or decrease the probability that the parent-child dyad will embark on a path toward antisocial outcomes. PMID:24280347

Developmental trajectory from early responses to transgressions to future antisocial behavior: evidence for the role of the parent-child relationship from two longitudinal studies.

PubMed

Kim, Sanghag; Kochanska, Grazyna; Boldt, Lea J; Nordling, Jamie Koenig; O'Bleness, Jessica J

2014-02-01

Parent-child relationships are critical in development, but much remains to be learned about the mechanisms of their impact. We examined the early parent-child relationship as a moderator of the developmental trajectory from children's affective and behavioral responses to transgressions to future antisocial, externalizing behavior problems in the Family Study (102 community mothers, fathers, and infants, followed through age 8) and the Play Study (186 low-income, diverse mothers and toddlers, followed for 10 months). The relationship quality was indexed by attachment security in the Family Study and maternal responsiveness in the Play Study. Responses to transgressions (tense discomfort and reparation) were observed in laboratory mishaps wherein children believed they had damaged a valued object. Antisocial outcomes were rated by parents. In both studies, early relationships moderated the future developmental trajectory: diminished tense discomfort predicted more antisocial outcomes, but only in insecure or unresponsive relationships. That risk was defused in secure or responsive relationships. Moderated mediation analyses in the Family Study indicated that the links between diminished tense discomfort and future antisocial behavior in insecure parent-child dyads were mediated by stronger discipline pressure from parents. By indirectly influencing future developmental sequelae, early relationships may increase or decrease the probability that the parent-child dyad will embark on a path toward antisocial outcomes.

Mechanical factors direct mouse aortic remodelling during early maturation

PubMed Central

Le, Victoria P.; Cheng, Jeffrey K.; Kim, Jungsil; Staiculescu, Marius C.; Ficker, Shawn W.; Sheth, Saahil C.; Bhayani, Siddharth A.; Mecham, Robert P.; Yanagisawa, Hiromi; Wagenseil, Jessica E.

2015-01-01

Numerous diseases have been linked to genetic mutations that lead to reduced amounts or disorganization of arterial elastic fibres. Previous work has shown that mice with reduced amounts of elastin (Eln+/−) are able to live a normal lifespan through cardiovascular adaptations, including changes in haemodynamic stresses, arterial geometry and arterial wall mechanics. It is not known if the timeline and presence of these adaptations are consistent in other mouse models of elastic fibre disease, such as those caused by the absence of fibulin-5 expression (Fbln5−/−). Adult Fbln5−/− mice have disorganized elastic fibres, decreased arterial compliance and high blood pressure. We examined mechanical behaviour of the aorta in Fbln5−/− mice through early maturation when the elastic fibres are being assembled. We found that the physiologic circumferential stretch, stress and modulus of Fbln5−/− aorta are maintained near wild-type levels. Constitutive modelling suggests that elastin contributions to the total stress are decreased, whereas collagen contributions are increased. Understanding how collagen fibre structure and mechanics compensate for defective elastic fibres to meet the mechanical requirements of the maturing aorta may help to better understand arterial remodelling in human elastinopathies. PMID:25652465

An Elaborate Data Set Characterizing the Mechanical Response of the Foot

PubMed Central

Erdemir, Ahmet; Sirimamilla, Pavana A.; Halloran, Jason P.; van den Bogert, Antonie J.

2010-01-01

Background Mechanical properties of the foot are responsible for its normal function and play a role in various clinical problems. Specifically, we are interested in quantification of foot mechanical properties to assist the development of computational models for movement analysis and detailed simulations of tissue deformation. Current available data are specific to a foot region and the loading scenarios are limited to a single direction. A data set that incorporates regional response, to quantify individual function of foot components, as well as overall response, to illustrate their combined operation, does not exist. Furthermore, combined three-dimensional loading scenarios while measuring the complete three-dimensional deformation response are lacking. When combined with an anatomical image data set, development of anatomically realistic and mechanically validated models becomes possible. Therefore, the goal of this study was to record and disseminate the mechanical response of a foot specimen, supported by imaging data. Method of Approach Robotic testing was conducted at the rear foot, forefoot, metatarsal heads, and the foot as a whole. Complex foot deformations were induced by single mode loading, e.g. compression, and combined loading, e.g. compression and shear. Small and large indenters were used for heel and metatarsal head loading; an elevated platform was utilized to isolate the rear foot and forefoot; and a full platform compressed the whole foot. Three-dimensional tool movements and reaction loads were recorded simultaneously. Computed tomography scans of the same specimen were collected for anatomical reconstruction a-priori. Results Three-dimensional mechanical response of the specimen was nonlinear and viscoelastic. A low stiffness region was observed starting with contact between the tool and foot regions, increasing with loading. Loading and unloading response portrayed hysteresis. Loading range ensured capturing the toe and linear regions of

Capturing early signs of deterioration: the dutch-early-nurse-worry-indicator-score and its value in the Rapid Response System.

PubMed

Douw, Gooske; Huisman-de Waal, Getty; van Zanten, Arthur R H; van der Hoeven, Johannes G; Schoonhoven, Lisette

2017-09-01

To determine the predictive value of individual and combined dutch-early-nurse-worry-indicator-score indicators at various Early Warning Score levels, differentiating between Early Warning Scores reaching the trigger threshold to call a rapid response team and Early Warning Score levels not reaching this point. Dutch-early-nurse-worry-indicator-score comprises nine indicators underlying nurses' 'worry' about a patient's condition. All indicators independently show significant association with unplanned intensive care/high dependency unit admission or unexpected mortality. Prediction of this outcome improved by adding the dutch-early-nurse-worry-indicator-score indicators to an Early Warning Score based on vital signs. An observational cohort study was conducted on three surgical wards in a tertiary university-affiliated teaching hospital. Included were surgical, native-speaking, adult patients. Nurses scored presence of 'worry' and/or dutch-early-nurse-worry-indicator-score indicators every shift or when worried. Vital signs were measured according to the prevailing protocol. Unplanned intensive care/high dependency unit admission or unexpected mortality was the composite endpoint. Percentages of 'worry' and dutch-early-nurse-worry-indicator-score indicators were calculated at various Early Warning Score levels in control and event groups. Entering all dutch-early-nurse-worry-indicator-score indicators in a multiple logistic regression analysis, we calculated a weighted score and calculated sensitivity, specificity, positive predicted value and negative predicted value for each possible total score. In 3522 patients, 102 (2·9%) had an unplanned intensive care/high dependency unit admissions (n = 97) or unexpected mortality (n = 5). Patients with such events and only slightly changed vital signs had significantly higher percentages of 'worry' and dutch-early-nurse-worry-indicator-score indicators expressed than patients in the control group. Increasing number

Response to Therapy Following Retreatment of Serofast Early Syphilis Patients With Benzathine Penicillin

PubMed Central

Seña, Arlene C.; Wolff, Mark; Behets, Frieda; Van Damme, Kathleen; Martin, David H.; Leone, Peter; McNeil, Linda; Hook, Edward W.

2013-01-01

Persistent nontreponemal titers after treatment are common among patients with early syphilis. We retreated 82 human immunodeficiency virus–negative early syphilis participants who were serofast at 6 months using benzathine penicillin. Only 27% exhibited serological response after retreatment and after an additional 6 months of follow-up. PMID:23118269

Evolution of attention mechanisms for early visual processing

NASA Astrophysics Data System (ADS)

Müller, Thomas; Knoll, Alois

2011-03-01

Early visual processing as a method to speed up computations on visual input data has long been discussed in the computer vision community. The general target of a such approaches is to filter nonrelevant information from the costly higher-level visual processing algorithms. By insertion of this additional filter layer the overall approach can be speeded up without actually changing the visual processing methodology. Being inspired by the layered architecture of the human visual processing apparatus, several approaches for early visual processing have been recently proposed. Most promising in this field is the extraction of a saliency map to determine regions of current attention in the visual field. Such saliency can be computed in a bottom-up manner, i.e. the theory claims that static regions of attention emerge from a certain color footprint, and dynamic regions of attention emerge from connected blobs of textures moving in a uniform way in the visual field. Top-down saliency effects are either unconscious through inherent mechanisms like inhibition-of-return, i.e. within a period of time the attention level paid to a certain region automatically decreases if the properties of that region do not change, or volitional through cognitive feedback, e.g. if an object moves consistently in the visual field. These bottom-up and top-down saliency effects have been implemented and evaluated in a previous computer vision system for the project JAST. In this paper an extension applying evolutionary processes is proposed. The prior vision system utilized multiple threads to analyze the regions of attention delivered from the early processing mechanism. Here, in addition, multiple saliency units are used to produce these regions of attention. All of these saliency units have different parameter-sets. The idea is to let the population of saliency units create regions of attention, then evaluate the results with cognitive feedback and finally apply the genetic mechanism

Cellular and molecular mechanisms for the bone response to mechanical loading

NASA Technical Reports Server (NTRS)

Bloomfield, S. A.

2001-01-01

To define the cellular and molecular mechanisms for the osteogenic response of bone to increased loading, several key steps must be defined: sensing of the mechanical signal by cells in bone, transduction of the mechanical signal to a biochemical one, and transmission of that biochemical signal to effector cells. Osteocytes are likely to serve as sensors of loading, probably via interstitial fluid flow produced during loading. Evidence is presented for the role of integrins, the cell's actin cytoskeleton, G proteins, and various intracellular signaling pathways in transducing that mechanical signal to a biochemical one. Nitric oxide, prostaglandins, and insulin-like growth factors all play important roles in these pathways. There is growing evidence for modulation of these mechanotransduction steps by endocrine factors, particularly parathyroid hormone and estrogen. The efficiency of this process is also impaired in the aged animal, yet what remains undefined is at what step mechanotransduction is affected.

Oestrogen status in relation to the early training responses in human thumb adductor muscles.

PubMed

Onambele, G N L; Bruce, S A; Woledge, R C

2006-09-01

The aims of this study were to identify the mechanisms for the early response to training in women of different oestrogen status and to determine whether any oestrogen and exercise effects on these would be additive. We monitored training (ten 5-s contractions per day for 12 weeks)-induced changes in the size, strength, voluntary activation capacity and index of crossbridge force state (i.e. rapid stretch to isometric torque ratio), in the thumb adductor muscles of postmenopausal [eight who had never used, and 14 who were using, hormone replacement therapy (HRT)] and seven premenopausal eumenorrhoeic women. The contralateral untrained muscle was used as a control. There was a significant effect of oestrogen status on the magnitude of training-induced strength increment, with the non-HRT postmenopausal group exhibiting the greatest benefits (28 +/- 6%, P = 0.024) from training. There were no significant or commensurate changes in either cross-sectional area or voluntary activation capacity. The index of crossbridge force state improved most in the no-HRT group (19 +/- 7%, P < 0.05). Presence, rather than absence of oestrogen, is associated with relatively higher muscle function which limits the potential for any further training-induced increments in muscle performance, as would be expected if the muscle strengthening actions of training and oestrogen share a common, partially saturable physiological pathway. The mechanism that is involved in the early training-induced strength increment in the three differing oestrogen groups cannot be due to increased size or recruitment. It would appear instead that increased motor unit firing frequency is involved.

Early life adversity influences stress response association with smoking relapse.

PubMed

al'Absi, Mustafa; Lemieux, Andrine; Westra, Ruth; Allen, Sharon

2017-11-01

We examined the hypothesis that stress-related blunting of cortisol in smokers is particularly pronounced in those with a history of severe life adversity. The two aims of this study were first to examine hormonal, craving, and withdrawal symptoms during ad libitum smoking and after the first 24 h of abstinence in smokers who experienced high or low levels of adversity. Second, we sought to examine the relationship between adversity and hypothalamic-pituitary-adrenal (HPA) hormones to predict relapse during the first month of a smoking cessation attempt. Hormonal and self-report measures were collected from 103 smokers (49 women) during ad libitum smoking and after the first 24 h of abstinence. HPA hormones were measured during baseline rest and in response to acute stress in both conditions. All smokers were interested in smoking cessation, and we prospectively used stress response measures to predict relapse during the first 4 weeks of the smoking cessation attempt. The results showed that high adversity was associated with higher distress and smoking withdrawal symptoms. High level of early life adversity was associated with elevated HPA activity, which was found in both salivary and plasma cortisol. Enhanced adrenocorticotropic hormone (ACTH) stress response was evident in high-adversity but not in low-adversity relapsers. This study demonstrated that early life adversity is associated with stress-related HPA responses. The study also demonstrated that, among smokers who experienced a high level of life adversity, heightened ACTH and cortisol responses were linked with increased risk for smoking relapse.

Language experience enhances early cortical pitch-dependent responses

PubMed Central

Krishnan, Ananthanarayan; Gandour, Jackson T.; Ananthakrishnan, Saradha; Vijayaraghavan, Venkatakrishnan

2014-01-01

Pitch processing at cortical and subcortical stages of processing is shaped by language experience. We recently demonstrated that specific components of the cortical pitch response (CPR) index the more rapidly-changing portions of the high rising Tone 2 of Mandarin Chinese, in addition to marking pitch onset and sound offset. In this study, we examine how language experience (Mandarin vs. English) shapes the processing of different temporal attributes of pitch reflected in the CPR components using stimuli representative of within-category variants of Tone 2. Results showed that the magnitude of CPR components (Na-Pb and Pb-Nb) and the correlation between these two components and pitch acceleration were stronger for the Chinese listeners compared to English listeners for stimuli that fell within the range of Tone 2 citation forms. Discriminant function analysis revealed that the Na-Pb component was more than twice as important as Pb-Nb in grouping listeners by language affiliation. In addition, a stronger stimulus-dependent, rightward asymmetry was observed for the Chinese group at the temporal, but not frontal, electrode sites. This finding may reflect selective recruitment of experience-dependent, pitch-specific mechanisms in right auditory cortex to extract more complex, time-varying pitch patterns. Taken together, these findings suggest that long-term language experience shapes early sensory level processing of pitch in the auditory cortex, and that the sensitivity of the CPR may vary depending on the relative linguistic importance of specific temporal attributes of dynamic pitch. PMID:25506127

Passive and active response of bacteria under mechanical compression

NASA Astrophysics Data System (ADS)

Garces, Renata; Miller, Samantha; Schmidt, Christoph F.; Byophysics Team; Institute of Medical Sciences Collaboration

Bacteria display simple but fascinating cellular structures and geometries. Their shapes are the result of the interplay between osmotic pressure and cell wall construction. Typically, bacteria maintain a high difference of osmotic pressure (on the order of 1 atm) to the environment. This pressure difference (turgor pressure) is supported by the cell envelope, a composite of lipid membranes and a rigid cell wall. The response of the cell envelope to mechanical perturbations such as geometrical confinements is important for the cells survival. Another key property of bacteria is the ability to regulate turgor pressure after abrupt changes of external osmotic conditions. This response relies on the activity of mechanosensitive (MS) channels: membrane proteins that release solutes in response to excessive stress in the cell envelope. We here present experimental data on the mechanical response of the cell envelope and on turgor regulation of bacteria subjected to compressive forces. We indent living cells with micron-sized beads attached to the cantilever of an atomic force microscope (AFM). This approach ensures global deformation of the cell. We show that such mechanical loading is sufficient to gate mechanosensitive channels in isosmotic conditions.

Early transcriptional responses of internalization defective Brucella abortus mutants in professional phagocytes, RAW 264.7.

PubMed

Cha, Seung Bin; Lee, Won Jung; Shin, Min Kyoung; Jung, Myung Hwan; Shin, Seung Won; Yoo, An Na; Kim, Jong Wan; Yoo, Han Sang

2013-06-27

Brucella abortus is an intracellular zoonotic pathogen which causes undulant fever, endocarditis, arthritis and osteomyelitis in human and abortion and infertility in cattle. This bacterium is able to invade and replicate in host macrophage instead of getting removed by this defense mechanism. Therefore, understanding the interaction between virulence of the bacteria and the host cell is important to control brucellosis. Previously, we generated internalization defective mutants and analyzed the envelope proteins. The present study was undertaken to evaluate the changes in early transcriptional responses between wild type and internalization defective mutants infected mouse macrophage, RAW 264.7. Both of the wild type and mutant infected macrophages showed increased expression levels in proinflammatory cytokines, chemokines, apoptosis and G-protein coupled receptors (Gpr84, Gpr109a and Adora2b) while the genes related with small GTPase which mediate intracellular trafficking was decreased. Moreover, cytohesin 1 interacting protein (Cytip) and genes related to ubiquitination (Arrdc3 and Fbxo21) were down-regulated, suggesting the survival strategy of this bacterium. However, we could not detect any significant changes in the mutant infected groups compared to the wild type infected group. In summary, it was very difficult to clarify the alterations in host cellular transcription in response to infection with internalization defective mutants. However, we found several novel gene changes related to the GPCR system, ubiquitin-proteosome system, and growth arrest and DNA damages in response to B. abortus infection. These findings may contribute to a better understanding of the molecular mechanisms underlying host-pathogen interactions and need to be studied further.

Discrete β-adrenergic mechanisms regulate early and late erythropoiesis in erythropoietin-resistant anemia.

PubMed

Hasan, Shirin; Mosier, Michael J; Szilagyi, Andrea; Gamelli, Richard L; Muthumalaiappan, Kuzhali

2017-10-01

Anemia of critical illness is resistant to exogenous erythropoietin. Packed red blood cells transfusions is the only treatment option, and despite related cost and morbidity, there is a need for alternate strategies. Erythrocyte development can be divided into erythropoietin-dependent and erythropoietin-independent stages. We have shown previously that erythropoietin-dependent development is intact in burn patients and the erythropoietin-independent early commitment stage, which is regulated by β1/β2-adrenergic mechanisms, is compromised. Utilizing the scald burn injury model, we studied erythropoietin-independent late maturation stages and the effect of β1/β2, β-2, or β-3 blockade in burn mediated erythropoietin-resistant anemia. Burn mice were randomized to receive daily injections of propranolol (nonselective β1/β2 antagonist), nadolol (long-acting β1/β2 antagonist), butoxamine (selective β2 antagonist), or SR59230A (selective β3 antagonist) for 6 days after burn. Total bone marrow cells were characterized as nonerythroid cells, early and late erythroblasts, nucleated orthochromatic erythroblasts and enucleated reticulocyte subsets using CD71, Ter119, and Syto-16 by flow cytometry. Multipotential progenitors were probed for MafB expressing cells. Although propranolol improved early and late erythroblasts, only butoxamine and selective β3-antagonist administrations were positively reflected in the peripheral blood hemoglobin and red blood cells count. While burn impeded early commitment and late maturation stages, β1/β2 antagonism increased the early erythroblasts through commitment stages via β2 specific MafB regulation. β3 antagonism was more effective in improving overall red blood cells through late maturation stages. The study unfolds novel β2 and β3 adrenergic mechanisms orchestrating erythropoietin resistant anemia after burn, which impedes both the early commitment stage and the late maturation stages, respectively. Copyright © 2017

The Impact of Early Substance Use Disorder Treatment Response on Treatment Outcomes Among Pregnant Women With Primary Opioid Use.

PubMed

Tuten, Michelle; Fitzsimons, Heather; Hochheimer, Martin; Jones, Hendree E; Chisolm, Margaret S

2018-03-13

This study examined the impact of early patient response on treatment utilization and substance use among pregnant participants enrolled in substance use disorder (SUD) treatment. Treatment responders (TRs) and treatment nonresponders (TNRs) were compared on pretreatment and treatment measures. Regression models predicted treatment utilization and substance use. TR participants attended more treatment and had lower rates of substance use relative to TNR participants. Regression models for treatment utilization and substance use were significant. Maternal estimated gestational age (EGA) and baseline cocaine use were negatively associated with treatment attendance. Medication-assisted treatment, early treatment response, and baseline SUD treatment were positively associated with treatment attendance. Maternal EGA was negatively associated with counseling attendance; early treatment response was positively associated with counseling attendance. Predictors of any substance use at 1 month were maternal education, EGA, early treatment nonresponse, and baseline cocaine use. The single predictor of any substance use at 2 months was early treatment nonresponse. Predictors of opioid use at 1 month were maternal education, EGA, early treatment nonresponse, and baseline SUD treatment. Predictors of opioid use at 2 months were early treatment nonresponse, and baseline cocaine and marijuana use. Predictors of cocaine use at 1 month were early treatment nonresponse, baseline cocaine use, and baseline SUD treatment. Predictors of cocaine use at 2 months were early treatment nonresponse and baseline cocaine use. Early treatment response predicts more favorable maternal treatment utilization and substance use outcomes. Treatment providers should implement interventions to maximize patient early response to treatment.

A Comparison of Responsive Interventions on Kindergarteners' Early Reading Achievement

ERIC Educational Resources Information Center

Little, Mary E.; Rawlinson, D'Ann; Simmons, Deborah C.; Kim, Minjung; Kwok, Oi-man; Hagan-Burke, Shanna; Simmons, Leslie E.; Fogarty, Melissa; Oslund, Eric; Coyne, Michael D.

2012-01-01

This study compared the effects of Tier 2 reading interventions that operated in response-to-intervention contexts. Kindergarten children (N = 90) who were identified as at risk for reading difficulties were stratified by school and randomly assigned to receive (a) Early Reading Intervention (ERI; Pearson/Scott Foresman, 2004) modified in response…

An early history of T cell-mediated cytotoxicity.

PubMed

Golstein, Pierre; Griffiths, Gillian M

2018-04-16

After 60 years of intense fundamental research into T cell-mediated cytotoxicity, we have gained a detailed knowledge of the cells involved, specific recognition mechanisms and post-recognition perforin-granzyme-based and FAS-based molecular mechanisms. What could not be anticipated at the outset was how discovery of the mechanisms regulating the activation and function of cytotoxic T cells would lead to new developments in cancer immunotherapy. Given the profound recent interest in therapeutic manipulation of cytotoxic T cell responses, it is an opportune time to look back on the early history of the field. This Timeline describes how the early findings occurred and eventually led to current therapeutic applications.

Diffusion MRI in early cancer therapeutic response assessment

PubMed Central

Galbán, C. J.; Hoff, B. A.; Chenevert, T. L.; Ross, B. D.

2016-01-01

Imaging biomarkers for the predictive assessment of treatment response in patients with cancer earlier than standard tumor volumetric metrics would provide new opportunities to individualize therapy. Diffusion-weighted MRI (DW-MRI), highly sensitive to microenvironmental alterations at the cellular level, has been evaluated extensively as a technique for the generation of quantitative and early imaging biomarkers of therapeutic response and clinical outcome. First demonstrated in a rodent tumor model, subsequent studies have shown that DW-MRI can be applied to many different solid tumors for the detection of changes in cellularity as measured indirectly by an increase in the apparent diffusion coefficient (ADC) of water molecules within the lesion. The introduction of quantitative DW-MRI into the treatment management of patients with cancer may aid physicians to individualize therapy, thereby minimizing unnecessary systemic toxicity associated with ineffective therapies, saving valuable time, reducing patient care costs and ultimately improving clinical outcome. This review covers the theoretical basis behind the application of DW-MRI to monitor therapeutic response in cancer, the analytical techniques used and the results obtained from various clinical studies that have demonstrated the efficacy of DW-MRI for the prediction of cancer treatment response. PMID:26773848

DNA Methylation: A Mechanism for Embedding Early Life Experiences in the Genome

ERIC Educational Resources Information Center

Szyf, Moshe; Bick, Johanna

2013-01-01

Although epidemiological data provide evidence that early life experience plays a critical role in human development, the mechanism of how this works remains in question. Recent data from human and animal literature suggest that epigenetic changes, such as DNA methylation, are involved not only in cellular differentiation but also in the…

Arabidopsis thaliana responses to mechanical stimulation do not require ETR1 or EIN2

NASA Technical Reports Server (NTRS)

Johnson, K. A.; Sistrunk, M. L.; Polisensky, D. H.; Braam, J.; McIntire, L. V. (Principal Investigator)

1998-01-01

Plants exposed to repetitive touch or wind are generally shorter and stockier than sheltered plants. These mechanostimulus-induced developmental changes are termed thigmomorphogenesis and may confer resistance to subsequent stresses. An early response of Arabidopsis thaliana to touch or wind is the up-regulation of TCH (touch) gene expression. The signal transduction pathway that leads to mechanostimulus responses is not well defined. A role for ethylene has been proposed based on the observation that mechanostimulation of plants leads to ethylene evolution and exogenous ethylene leads to thigmomorphogenetic-like changes. To determine whether ethylene has a role in plant responses to mechanostimulation, we assessed the ability of two ethylene-insensitive mutants, etr1-3 and ein2-1, to undergo thigmomorphogenesis and TCH gene up-regulation of expression. The ethylene-insensitive mutants responded to wind similarly to the wild type, with a delay in flowering, decrease in inflorescence elongation rate, shorter mature primary inflorescences, more rosette paraclades, and appropriate TCH gene expression changes. Also, wild-type and mutant Arabidopsis responded to vibrational stimulation, with an increase in hypocotyl elongation and up-regulation of TCH gene expression. We conclude that the ETR1 and EIN2 protein functions are not required for the developmental and molecular responses to mechanical stimulation.

Early prediction of blonanserin response in Japanese patients with schizophrenia.

PubMed

Kishi, Taro; Matsuda, Yuki; Fujita, Kiyoshi; Iwata, Nakao

2014-01-01

Blonanserin is a second-generation antipsychotic used for the treatment of schizophrenia in Japan and Korea. The present study aimed to examine early prediction of blonanserin in patients with schizophrenia. An 8-week, prospective, single-arm, flexible-dose clinical trial of blonanserin in patients with schizophrenia was conducted under real-world conditions. The inclusion criteria were antipsychotic naïve, and first-episode schizophrenia patients or schizophrenia patients with no consumption of any antipsychotic medication for more than 4 weeks before enrollment in this study. The positive predictive value, negative predictive value, sensitivity, specificity, and predictive power were calculated for the response status at week 4 to predict the subsequent response at week 8. Thirty-seven patients were recruited (56.8% of them had first-episode schizophrenia), and 28 (75.7%) completed the trial. At week 8, blonanserin was associated with a significant improvement in the Positive and Negative Syndrome Scale (PANSS) total score (P<0.0001) and in positive (P<0.0001), negative (P<0.0001), and general subscale scores (P<0.0001). In terms of percentage improvement of PANSS total scores from baseline to week 8, 64.9% of patients showed a ≥20% reduction in the PANSS total score and 48.6% showed a ≥30% reduction. However, 8.1% of patients experienced at least one adverse event. Using the 20% reduction in the PANSS total score at week 4 as a definition of an early response, the negative predictive values for later responses (ie, reductions of ≥30 and ≥40 in the PANSS total scores) were 88.9% and 94.1%, respectively. The specificities were 80.0% and 51.6%, respectively. Our results suggest that the blonanserin response at week 4 could predict the later response at week 8.

Early prediction of blonanserin response in Japanese patients with schizophrenia

PubMed Central

Kishi, Taro; Matsuda, Yuki; Fujita, Kiyoshi; Iwata, Nakao

2014-01-01

Background Blonanserin is a second-generation antipsychotic used for the treatment of schizophrenia in Japan and Korea. The present study aimed to examine early prediction of blonanserin in patients with schizophrenia. Methods An 8-week, prospective, single-arm, flexible-dose clinical trial of blonanserin in patients with schizophrenia was conducted under real-world conditions. The inclusion criteria were antipsychotic naïve, and first-episode schizophrenia patients or schizophrenia patients with no consumption of any antipsychotic medication for more than 4 weeks before enrollment in this study. The positive predictive value, negative predictive value, sensitivity, specificity, and predictive power were calculated for the response status at week 4 to predict the subsequent response at week 8. Results Thirty-seven patients were recruited (56.8% of them had first-episode schizophrenia), and 28 (75.7%) completed the trial. At week 8, blonanserin was associated with a significant improvement in the Positive and Negative Syndrome Scale (PANSS) total score (P<0.0001) and in positive (P<0.0001), negative (P<0.0001), and general subscale scores (P<0.0001). In terms of percentage improvement of PANSS total scores from baseline to week 8, 64.9% of patients showed a ≥20% reduction in the PANSS total score and 48.6% showed a ≥30% reduction. However, 8.1% of patients experienced at least one adverse event. Using the 20% reduction in the PANSS total score at week 4 as a definition of an early response, the negative predictive values for later responses (ie, reductions of ≥30 and ≥40 in the PANSS total scores) were 88.9% and 94.1%, respectively. The specificities were 80.0% and 51.6%, respectively. Conclusion Our results suggest that the blonanserin response at week 4 could predict the later response at week 8. PMID:25285009

Cell wall pectic arabinans influence the mechanical properties of Arabidopsis thaliana inflorescence stems and their response to mechanical stress.

PubMed

Verhertbruggen, Yves; Marcus, Susan E; Chen, Jianshe; Knox, J Paul

2013-08-01

Little is known of the dynamics of plant cell wall matrix polysaccharides in response to the impact of mechanical stress on plant organs. The capacity of the imposition of a mechanical stress (periodic brushing) to reduce the height of the inflorescence stem of Arabidopsis thaliana seedlings has been used to study the role of pectic arabinans in the mechanical properties and stress responsiveness of a plant organ. The arabinan-deficient-1 (arad1) mutation that affects arabinan structures in epidermal cell walls of inflorescence stems is demonstrated to reduce the impact on inflorescence stem heights caused by mechanical stress. The arabinan-deficient-2 (arad2) mutation, that does not have detectable impact on arabinan structures, is also shown to reduce the impact on stem heights caused by mechanical stress. The LM13 linear arabinan epitope is specifically detected in epidermal cell walls of the younger, flexible regions of inflorescence stems and increases in abundance at the base of inflorescence stems in response to an imposed mechanical stress. The strain (percentage deformation) of stem epidermal cells in the double mutant arad1 × arad2 is lower in unbrushed plants than in wild-type plants, but rises to wild-type levels in response to brushing. The study demonstrates the complexity of arabinan structures within plant cell walls and also that their contribution to cell wall mechanical properties is a factor influencing responsiveness to mechanical stress.

Mechanical response of two polyimides through coarse-grained molecular dynamics simulations

NASA Astrophysics Data System (ADS)

Sudarkodi, V.; Sooraj, K.; Nair, Nisanth N.; Basu, Sumit; Parandekar, Priya V.; Sinha, Nishant K.; Prakash, Om; Tsotsis, Tom

2018-03-01

Coarse-grained molecular dynamics (MD) simulations allow us to predict the mechanical responses of polymers, starting merely with a description of their molecular architectures. It is interesting to ask whether, given two competing molecular architectures, coarse-grained MD simulations can predict the differences that can be expected in their mechanical responses. We have studied two crosslinked polyimides PMR15 and HFPE52—both used in high- temperature applications—to assess whether the subtle differences in their uniaxial stress-strain responses, revealed by experiments, can be reproduced by carefully coarse-grained MD models. The coarse graining procedure for PMR15 is outlined in this work, while the coarse grain forcefields for HFPE52 are borrowed from an earlier one (Pandiyan et al 2015 Macromol. Theory Simul. 24 513-20). We show that the stress-strain responses of both these polyimides are qualitatively reproduced, and important insights into their deformation and failure mechanisms are obtained. More importantly, the differences in the molecular architecture between the polyimides carry over to the differences in the stress-strain responses in a manner that parallels the experimental results. A critical assessment of the successes and shortcomings of predicting mechanical responses through coarse-grained MD simulations has been made.

Drought-Responsive Mechanisms in Plant Leaves Revealed by Proteomics.

PubMed

Wang, Xiaoli; Cai, Xiaofeng; Xu, Chenxi; Wang, Quanhua; Dai, Shaojun

2016-10-18

Plant drought tolerance is a complex trait that requires a global view to understand its underlying mechanism. The proteomic aspects of plant drought response have been extensively investigated in model plants, crops and wood plants. In this review, we summarize recent proteomic studies on drought response in leaves to reveal the common and specialized drought-responsive mechanisms in different plants. Although drought-responsive proteins exhibit various patterns depending on plant species, genotypes and stress intensity, proteomic analyses show that dominant changes occurred in sensing and signal transduction, reactive oxygen species scavenging, osmotic regulation, gene expression, protein synthesis/turnover, cell structure modulation, as well as carbohydrate and energy metabolism. In combination with physiological and molecular results, proteomic studies in leaves have helped to discover some potential proteins and/or metabolic pathways for drought tolerance. These findings provide new clues for understanding the molecular basis of plant drought tolerance.

Drought-Responsive Mechanisms in Plant Leaves Revealed by Proteomics

PubMed Central

Wang, Xiaoli; Cai, Xiaofeng; Xu, Chenxi; Wang, Quanhua; Dai, Shaojun

2016-01-01

Plant drought tolerance is a complex trait that requires a global view to understand its underlying mechanism. The proteomic aspects of plant drought response have been extensively investigated in model plants, crops and wood plants. In this review, we summarize recent proteomic studies on drought response in leaves to reveal the common and specialized drought-responsive mechanisms in different plants. Although drought-responsive proteins exhibit various patterns depending on plant species, genotypes and stress intensity, proteomic analyses show that dominant changes occurred in sensing and signal transduction, reactive oxygen species scavenging, osmotic regulation, gene expression, protein synthesis/turnover, cell structure modulation, as well as carbohydrate and energy metabolism. In combination with physiological and molecular results, proteomic studies in leaves have helped to discover some potential proteins and/or metabolic pathways for drought tolerance. These findings provide new clues for understanding the molecular basis of plant drought tolerance. PMID:27763546

The early response during the interaction of fungal phytopathogen and host plant.

PubMed

Shen, Yilin; Liu, Na; Li, Chuang; Wang, Xin; Xu, Xiaomeng; Chen, Wan; Xing, Guozhen; Zheng, Wenming

2017-05-01

Plants can be infected by a variety of pathogens, most of which can cause severe economic losses. The plants resist the invasion of pathogens via the innate or acquired immune system for surviving biotic stress. The associations between plants and pathogens are sophisticated beyond imaging and the interactions between them can occur at a very early stage after their touching each other. A number of researchers in the past decade have shown that many biochemical events appeared even as early as 5 min after their touching for plant disease resistance response. The early molecular interactions of plants and pathogens are likely to involve protein phosphorylation, ion fluxes, reactive oxygen species (ROS) and other signalling transduction. Here, we reviewed the recent progress in the study for molecular interaction response of fungal pathogens and host plant at the early infection stage, which included many economically important crop fungal pathogens such as cereal rust fungi, tomato Cladosporium fulvum , rice blast and so on. By dissecting the earlier infection stage of the diseases, the avirulent/virulent genes of pathogen or resistance genes of plant could be defined more clearly and accurately, which would undoubtedly facilitate fungal pathogenesis study and resistant crop breeding. © 2017 The Authors.

The early response during the interaction of fungal phytopathogen and host plant

PubMed Central

Shen, Yilin; Liu, Na; Li, Chuang; Wang, Xin; Xu, Xiaomeng; Chen, Wan; Xing, Guozhen

2017-01-01

Plants can be infected by a variety of pathogens, most of which can cause severe economic losses. The plants resist the invasion of pathogens via the innate or acquired immune system for surviving biotic stress. The associations between plants and pathogens are sophisticated beyond imaging and the interactions between them can occur at a very early stage after their touching each other. A number of researchers in the past decade have shown that many biochemical events appeared even as early as 5 min after their touching for plant disease resistance response. The early molecular interactions of plants and pathogens are likely to involve protein phosphorylation, ion fluxes, reactive oxygen species (ROS) and other signalling transduction. Here, we reviewed the recent progress in the study for molecular interaction response of fungal pathogens and host plant at the early infection stage, which included many economically important crop fungal pathogens such as cereal rust fungi, tomato Cladosporium fulvum, rice blast and so on. By dissecting the earlier infection stage of the diseases, the avirulent/virulent genes of pathogen or resistance genes of plant could be defined more clearly and accurately, which would undoubtedly facilitate fungal pathogenesis study and resistant crop breeding. PMID:28469008

Mechanical response tissue analyzer for estimating bone strength

NASA Technical Reports Server (NTRS)

Arnaud, Sara B.; Steele, Charles; Mauriello, Anthony

1991-01-01

One of the major concerns for extended space flight is weakness of the long bones of the legs, composed primarily of cortical bone, that functions to provide mechanical support. The strength of cortical bone is due to its complex structure, described simplistically as cylinders of parallel osteons composed of layers of mineralized collagen. The reduced mechanical stresses during space flight or immobilization of bone on Earth reduces the mineral content, and changes the components of its matrix and structure so that its strength is reduced. Currently, the established clinical measures of bone strength are indirect. The measures are based on determinations of mineral density by means of radiography, photon absorptiometry, and quantitative computer tomography. While the mineral content of bone is essential to its strength, there is growing awareness of the limitations of the measurement as the sole predictor of fracture risk in metabolic bone diseases, especially limitations of the measurement as the sole predictor of fracture risk in metabolic bone diseases, especially osteoporosis. Other experimental methods in clinical trials that more directly evaluate the physical properties of bone, and do not require exposure to radiation, include ultrasound, acoustic emission, and low-frequency mechanical vibration. The last method can be considered a direct measure of the functional capacity of a long bone since it quantifies the mechanical response to a stimulus delivered directly to the bone. A low frequency vibration induces a response (impedance) curve with a minimum at the resonant frequency, that a few investigators use for the evaluation of the bone. An alternative approach, the method under consideration, is to use the response curve as the basis for determination of the bone bending stiffness EI (E is the intrinsic material property and I is the cross-sectional moment of inertia) and mass, fundamental mechanical properties of bone.

Early bilingualism enhances mechanisms of false-belief reasoning.

PubMed

Kovács, Agnes Melinda

2009-01-01

In their first years, children's understanding of mental states seems to improve dramatically, but the mechanisms underlying these changes are still unclear. Such 'theory of mind' (ToM) abilities may arise during development, or have an innate basis, developmental changes reflecting limitations of other abilities involved in ToM tasks (e.g. inhibition). Special circumstances such as early bilingualism may enhance ToM development or other capacities required by ToM tasks. Here we compare 3-year-old bilinguals and monolinguals on a standard ToM task, a modified ToM task and a control task involving physical reasoning. The modified ToM task mimicked a language-switch situation that bilinguals often encounter and that could influence their ToM abilities. If such experience contributes to an early consolidation of ToM in bilinguals, they should be selectively enhanced in the modified task. In contrast, if bilinguals have an advantage due to better executive inhibitory abilities involved in ToM tasks, they should outperform monolinguals on both ToM tasks, inhibitory demands being similar. Bilingual children showed an advantage on the two ToM tasks but not on the control task. The precocious success of bilinguals may be associated with their well-developed control functions formed during monitoring and selecting languages.

Real-time scratch assay reveals mechanisms of early calcium signaling in breast cancer cells in response to wounding

PubMed Central

Pratt, Stephen J.P.; Hernández-Ochoa, Erick O.; Lee, Rachel M.; Ory, Eleanor C.; Lyons, James S.; Joca, Humberto C.; Johnson, Ashley; Thompson, Keyata; Bailey, Patrick; Lee, Cornell J.; Mathias, Trevor; Vitolo, Michele I.; Trudeau, Matt; Stains, Joseph P.; Ward, Christopher W.; Schneider, Martin F.; Martin, Stuart S.

2018-01-01

Aggressive cellular phenotypes such as uncontrolled proliferation and increased migration capacity engender cellular transformation, malignancy and metastasis. While genetic mutations are undisputed drivers of cancer initiation and progression, it is increasingly accepted that external factors are also playing a major role. Two recently studied modulators of breast cancer are changes in the cellular mechanical microenvironment and alterations in calcium homeostasis. While many studies investigate these factors separately in breast cancer cells, very few do so in combination. This current work sets a foundation to explore mechano-calcium relationships driving malignant progression in breast cancer. Utilizing real-time imaging of an in vitro scratch assay, we were able to resolve mechanically-sensitive calcium signaling in human breast cancer cells. We observed rapid initiation of intracellular calcium elevations within seconds in cells at the immediate wound edge, followed by a time-dependent increase in calcium in cells at distances up to 500μm from the scratch wound. Calcium signaling to neighboring cells away from the wound edge returned to baseline within seconds. Calcium elevations at the wound edge however, persisted for up to 50 minutes. Rigorous quantification showed that extracellular calcium was necessary for persistent calcium elevation at the wound edge, but intercellular signal propagation was dependent on internal calcium stores. In addition, intercellular signaling required extracellular ATP and activation of P2Y2 receptors. Through comparison of scratch-induced signaling from multiple cell lines, we report drastic reductions in response from aggressively tumorigenic and metastatic cells. The real-time scratch assay established here provides quantitative data on the molecular mechanisms that support rapid scratch-induced calcium signaling in breast cancer cells. These mechanisms now provide a clear framework for investigating which short-term calcium

Early disrupted neurovascular coupling and changed event level hemodynamic response function in type 2 diabetes: an fMRI study.

PubMed

Duarte, João V; Pereira, João M S; Quendera, Bruno; Raimundo, Miguel; Moreno, Carolina; Gomes, Leonor; Carrilho, Francisco; Castelo-Branco, Miguel

2015-10-01

Type 2 diabetes (T2DM) patients develop vascular complications and have increased risk for neurophysiological impairment. Vascular pathophysiology may alter the blood flow regulation in cerebral microvasculature, affecting neurovascular coupling. Reduced fMRI signal can result from decreased neuronal activation or disrupted neurovascular coupling. The uncertainty about pathophysiological mechanisms (neurodegenerative, vascular, or both) underlying brain function impairments remains. In this cross-sectional study, we investigated if the hemodynamic response function (HRF) in lesion-free brains of patients is altered by measuring BOLD (Blood Oxygenation Level-Dependent) response to visual motion stimuli. We used a standard block design to examine the BOLD response and an event-related deconvolution approach. Importantly, the latter allowed for the first time to directly extract the true shape of HRF without any assumption and probe neurovascular coupling, using performance-matched stimuli. We discovered a change in HRF in early stages of diabetes. T2DM patients show significantly different fMRI response profiles. Our visual paradigm therefore demonstrated impaired neurovascular coupling in intact brain tissue. This implies that functional studies in T2DM require the definition of HRF, only achievable with deconvolution in event-related experiments. Further investigation of the mechanisms underlying impaired neurovascular coupling is needed to understand and potentially prevent the progression of brain function decrements in diabetes.

Perceived early-life maternal care and the cortisol response to repeated psychosocial stress.

PubMed

Engert, Veronika; Efanov, Simona I; Dedovic, Katarina; Duchesne, Annie; Dagher, Alain; Pruessner, Jens C

2010-11-01

In the past decade, a body of animal and human research has revealed a profound influence of early-life experiences, ranging from variations in parenting behaviour to severe adversity, on hypothalamic-pituitary-adrenal axis regulation in adulthood. In our own previous studies, we have shown how variations in early-life parental care influence the development of the hippocampus and modify the cortisol awakening response. In the present study, we investigated the influence of early-life maternal care on cortisol, heart rate and subjective psychological responses to the repeated administration of a psychosocial laboratory stressor in a population of 63 healthy young adults. Low, medium and high early-life maternal care groups were identified using the Parental Bonding Instrument. Controlling for the effect of sex, we found an inverted u-shaped relation between increasing levels of maternal care and cortisol stress responsivity. Specifically, overall and stress-induced cortisol levels went from below normal in the low maternal care, to normal in the medium care, back to below normal in the high maternal care groups. We found no group differences with respect to heart rate and subjective psychological stress measures. Whereas low and high maternal care groups exhibited similarly low endocrine stress responses, their psychological profiles were opposed with increased levels of depression and anxiety and decreased self-esteem in the low care group. Sex was unequally distributed among maternal care groups, whereby the number of men with low maternal care was too small to allow introducing sex as a second between-group variable. We discuss the potential significance of this dissociation between endocrine and psychological parameters with respect to stress vulnerability and resistance for each maternal care group.

Effectiveness of Community-Based Early Intervention Based on Pivotal Response Treatment

ERIC Educational Resources Information Center

Smith, Isabel M.; Flanagan, Helen E.; Garon, Nancy; Bryson, Susan E.

2015-01-01

Preschoolers (n = 118) with autism spectrum disorder (ASD) participated in this prospective effectiveness study of an early intervention program. Treatment entailed parent training and therapist-implemented components, incorporating Pivotal Response Treatment and Positive Behaviour Support. Standardized ability and behavioural measures were…

Cellular Mechanisms of Gravitropic Response in Higher Plants

NASA Astrophysics Data System (ADS)

Medvedev, Sergei; Smolikova, Galina; Pozhvanov, Gregory; Suslov, Dmitry

The evolutionary success of land plants in adaptation to the vectorial environmental factors was based mainly on the development of polarity systems. In result, normal plant ontogenesis is based on the positional information. Polarity is a tool by which the developing plant organs and tissues are mapped and the specific three-dimensional structure of the organism is created. It is due to their polar organization plants are able to orient themselves relative to the gravity vector and different vectorial cues, and to respond adequately to various stimuli. Gravitation is one of the most important polarized environmental factor that guides the development of plant organisms in space. Every plant can "estimate" its position relative to the gravity vector and correct it, if necessary, by means of polarized growth. The direction and the magnitude of gravitational stimulus are constant during the whole plant ontogenesis. The key plant response to the action of gravity is gravitropism, i.e. the directed growth of organs with respect to the gravity vector. This response is a very convenient model to study the mechanisms of plant orientation in space. The present report is focused on the main cellular mechanisms responsible for graviropic bending in higher plants. These mechanisms and structures include electric polarization of plant cells, Ca ({2+) }gradients, cytoskeleton, G-proteins, phosphoinositides and the machinery responsible for asymmetric auxin distribution. Those mechanisms tightly interact demonstrating some hierarchy and multiple feedbacks. The Ca (2+) gradients provide the primary physiological basis of polarity in plant cells. Calcium ions influence on the bioelectric potentials, the organization of actin cytoskeleton, the activity of Ca (2+) -binding proteins and Ca (2+) -dependent protein kinases. Protein kinases modulate transcription factors activity thereby regulating the gene expression and switching the developmental programs. Actin cytoskeleton affects

Early life conditions that impact song learning in male zebra finches also impact neural and behavioral responses to song in females.

PubMed

Sewall, Kendra B; Anderson, Rindy C; Soha, Jill A; Peters, Susan; Nowicki, Stephen

2018-04-20

Early life stressors can impair song in songbirds by negatively impacting brain development and subsequent learning. Even in species in which only males sing, early life stressors might also impact female behavior and its underlying neural mechanisms, but fewer studies have examined this possibility. We manipulated brood size in zebra finches to simultaneously examine the effects of developmental stress on male song learning and female behavioral and neural response to song. Although adult male HVC volume was unaffected, we found that males from larger broods imitated tutor song less accurately. In females, early condition did not affect the direction of song preference: all females preferred tutor song over unfamiliar song in an operant test. However, treatment did affect the magnitude of behavioral response to song: females from larger broods responded less during song preference trials. This difference in activity level did not reflect boldness per se, as a separate measure of this trait did not differ with brood size. Additionally, in females we found a treatment effect on expression of the immediate early gene ZENK in response to tutor song in brain regions involved in song perception (dNCM) and social motivation (LSc.vl, BSTm, TnA), but not in a region implicated in song memory (CMM). These results are consistent with the hypothesis that developmental stressors that impair song learning in male zebra finches also influence perceptual and/or motivational processes in females. However, our results suggest that the learning of tutor song by females is robust to disturbance by developmental stress. © 2018 Wiley Periodicals, Inc. Develop Neurobiol, 2018. © 2018 Wiley Periodicals, Inc.

Recovery from severe H7N9 disease is associated with diverse response mechanisms dominated by CD8+ T cells

PubMed Central

Wang, Zhongfang; Wan, Yanmin; Qiu, Chenli; Quiñones-Parra, Sergio; Zhu, Zhaoqin; Loh, Liyen; Tian, Di; Ren, Yanqin; Hu, Yunwen; Zhang, Xiaoyan; Thomas, Paul G.; Inouye, Michael; Doherty, Peter C.; Kedzierska, Katherine; Xu, Jianqing

2015-01-01

The avian origin A/H7N9 influenza virus causes high admission rates (>99%) and mortality (>30%), with ultimately favourable outcomes ranging from rapid recovery to prolonged hospitalization. Using a multicolour assay for monitoring adaptive and innate immunity, here we dissect the kinetic emergence of different effector mechanisms across the spectrum of H7N9 disease and recovery. We find that a diversity of response mechanisms contribute to resolution and survival. Patients discharged within 2–3 weeks have early prominent H7N9-specific CD8+ T-cell responses, while individuals with prolonged hospital stays have late recruitment of CD8+/CD4+ T cells and antibodies simultaneously (recovery by week 4), augmented even later by prominent NK cell responses (recovery >30 days). In contrast, those who succumbed have minimal influenza-specific immunity and little evidence of T-cell activation. Our study illustrates the importance of robust CD8+ T-cell memory for protection against severe influenza disease caused by newly emerging influenza A viruses. PMID:25967273

A hydro-mechanical framework for early warning of rainfall-induced landslides (Invited)

NASA Astrophysics Data System (ADS)

Godt, J.; Lu, N.; Baum, R. L.

2013-12-01

Landslide early warning requires an estimate of the location, timing, and magnitude of initial movement, and the change in volume and momentum of material as it travels down a slope or channel. In many locations advance assessment of landslide location, volume, and momentum is possible, but prediction of landslide timing entails understanding the evolution of rainfall and soil-water conditions, and consequent effects on slope stability in real time. Existing schemes for landslide prediction generally rely on empirical relations between landslide occurrence and rainfall amount and duration, however, these relations do not account for temporally variable rainfall nor the variably saturated processes that control the hydro-mechanical response of hillside materials to rainfall. Although limited by the resolution and accuracy of rainfall forecasts and now-casts in complex terrain and by the inherent difficulty in adequately characterizing subsurface materials, physics-based models provide a general means to quantitatively link rainfall and landslide occurrence. To obtain quantitative estimates of landslide potential from physics-based models using observed or forecasted rainfall requires explicit consideration of the changes in effective stress that result from changes in soil moisture and pore-water pressures. The physics that control soil-water conditions are transient, nonlinear, hysteretic, and dependent on material composition and history. In order to examine the physical processes that control infiltration and effective stress in variably saturated materials, we present field and laboratory results describing intrinsic relations among soil water and mechanical properties of hillside materials. At the REV (representative elementary volume) scale, the interaction between pore fluids and solid grains can be effectively described by the relation between soil suction, soil water content, hydraulic conductivity, and suction stress. We show that these relations can be

The bradykinin B2 receptor in the early immune response against Listeria infection.

PubMed

Kaman, Wendy E; Wolterink, Arthur F W M; Bader, Michael; Boele, Linda C L; van der Kleij, Desiree

2009-02-01

The endogenous danger signal bradykinin was recently found implicated in the development of immunity against parasites via dendritic cells. We here report an essential role of the B(2) (B(2)R) bradykinin receptor in the early immune response against Listeria infection. Mice deficient in B(2)R (B(2)R(-/-) mice) were shown to suffer from increased hepatic bacterial burden and concomitant dramatic weight loss during infection with Listeria monocytogenes. Levels of cytokines known to play a pivotal role in the early phase immune response against L. monocytogenes, IL-12p70 and IFN-gamma, were reduced in B(2)R(-/-) mice. To extend these findings to the human system, we show that bradykinin potentiates the production of IL-12p70 in human monocyte-derived dendritic cells. Thus, we show that bradykinin and the B(2)R play a role in early innate immune functions during bacterial infection.

[Inflammasome and its role in immunological and inflammatory response at early stage of burns].

PubMed

Zhang, Fang; Li, Jiahui; Xia, Zhaofan

2014-06-01

Inflammasomes are large multi-protein complexes that serve as a platform for caspase-1 activation, and this process induces subsequent maturation and secretion of the proinflammatory cytokines IL-1β and IL-18, as well as pyroptosis. As an important component of the innate immune system, early activation of inflammasomes in a variety of immune cell subsets can mediate inflammatory response and immunological conditions after burn injury. Here, we review the current knowledge of inflammasomes and its role in immunological and inflammatory response at the early stage of burn injury.

The tonic response to the infant knee jerk as an early sign of cerebral palsy.

PubMed

Hamer, Elisa G; La Bastide-Van Gemert, Sacha; Boxum, Anke G; Dijkstra, Linze J; Hielkema, Tjitske; Jeroen Vermeulen, R; Hadders-Algra, Mijna

2018-04-01

Early identification of infants at risk of cerebral palsy (CP) is desirable in order to provide early intervention. We previously demonstrated differences in knee jerk responses between 3-month-old high risk and typically developing infants. To improve early identification by investigating whether the presence of tonic responses (continuous muscle activity occurring after the typical phasic response), clonus or contralateral responses to the knee jerk during infancy is associated with CP. Longitudinal EMG-study. We included 34 high-risk infants (median gestational age 31.9 weeks) who participated in the LEARN2MOVE 0-2 years trial. Video-recorded knee jerk EMG-assessments were performed during infancy (1-4 times). Developmental outcome was assessed at 21 months corrected age (CA). Binomial generalized estimating equations models with repeated measurements were fitted using predictor variables. Infants who later were diagnosed with CP (n = 18) showed more often than infants who were not diagnosed with CP i) tonic responses - from 4 months CA onwards, ii) clonus - from 13 months CA onwards, and iii) contralateral responses - from 15 months CA onwards. The main limitation is the relatively small sample size. The assessment of tonic responses to the knee jerk using EMG may be a valuable add-on tool to appraise a high risk of CP. Copyright © 2018 Elsevier B.V. All rights reserved.

Thermo-mechanical simulations of early-age concrete cracking with durability predictions

NASA Astrophysics Data System (ADS)

Havlásek, Petr; Šmilauer, Vít; Hájková, Karolina; Baquerizo, Luis

2017-09-01

Concrete performance is strongly affected by mix design, thermal boundary conditions, its evolving mechanical properties, and internal/external restraints with consequences to possible cracking with impaired durability. Thermo-mechanical simulations are able to capture those relevant phenomena and boundary conditions for predicting temperature, strains, stresses or cracking in reinforced concrete structures. In this paper, we propose a weakly coupled thermo-mechanical model for early age concrete with an affinity-based hydration model for thermal part, taking into account concrete mix design, cement type and thermal boundary conditions. The mechanical part uses B3/B4 model for concrete creep and shrinkage with isotropic damage model for cracking, able to predict a crack width. All models have been implemented in an open-source OOFEM software package. Validations of thermo-mechanical simulations will be presented on several massive concrete structures, showing excellent temperature predictions. Likewise, strain validation demonstrates good predictions on a restrained reinforced concrete wall and concrete beam. Durability predictions stem from induction time of reinforcement corrosion, caused by carbonation and/or chloride ingress influenced by crack width. Reinforcement corrosion in concrete struts of a bridge will serve for validation.

Early transcriptional responses of internalization defective Brucella abortus mutants in professional phagocytes, RAW 264.7

PubMed Central

2013-01-01

Background Brucella abortus is an intracellular zoonotic pathogen which causes undulant fever, endocarditis, arthritis and osteomyelitis in human and abortion and infertility in cattle. This bacterium is able to invade and replicate in host macrophage instead of getting removed by this defense mechanism. Therefore, understanding the interaction between virulence of the bacteria and the host cell is important to control brucellosis. Previously, we generated internalization defective mutants and analyzed the envelope proteins. The present study was undertaken to evaluate the changes in early transcriptional responses between wild type and internalization defective mutants infected mouse macrophage, RAW 264.7. Results Both of the wild type and mutant infected macrophages showed increased expression levels in proinflammatory cytokines, chemokines, apoptosis and G-protein coupled receptors (Gpr84, Gpr109a and Adora2b) while the genes related with small GTPase which mediate intracellular trafficking was decreased. Moreover, cytohesin 1 interacting protein (Cytip) and genes related to ubiquitination (Arrdc3 and Fbxo21) were down-regulated, suggesting the survival strategy of this bacterium. However, we could not detect any significant changes in the mutant infected groups compared to the wild type infected group. Conclusions In summary, it was very difficult to clarify the alterations in host cellular transcription in response to infection with internalization defective mutants. However, we found several novel gene changes related to the GPCR system, ubiquitin-proteosome system, and growth arrest and DNA damages in response to B. abortus infection. These findings may contribute to a better understanding of the molecular mechanisms underlying host-pathogen interactions and need to be studied further. PMID:23802650

Early Gag Immunodominance of the HIV-Specific T-Cell Response during Acute/Early Infection Is Associated with Higher CD8+ T-Cell Antiviral Activity and Correlates with Preservation of the CD4+ T-Cell Compartment

PubMed Central

Ghiglione, Yanina; Falivene, Juliana; Socias, María Eugenia; Laufer, Natalia; Coloccini, Romina Soledad; Rodriguez, Ana María; Ruiz, María Julia; Pando, María Ángeles; Giavedoni, Luis David; Cahn, Pedro; Sued, Omar; Salomon, Horacio; Gherardi, María Magdalena

2013-01-01

The important role of the CD8+ T-cell response on HIV control is well established. Moreover, the acute phase of infection represents a proper scenario to delineate the antiviral cellular functions that best correlate with control. Here, multiple functional aspects (specificity, ex vivo viral inhibitory activity [VIA] and polyfunctionality) of the HIV-specific CD8+ T-cell subset arising early after infection, and their association with disease progression markers, were examined. Blood samples from 44 subjects recruited within 6 months from infection (primary HIV infection [PHI] group), 16 chronically infected subjects, 11 elite controllers (EC), and 10 healthy donors were obtained. Results indicated that, although Nef dominated the anti-HIV response during acute/early infection, a higher proportion of early anti-Gag T cells correlated with delayed progression. Polyfunctional HIV-specific CD8+ T cells were detected at early time points but did not associate with virus control. Conversely, higher CD4+ T-cell set points were observed in PHI subjects with higher HIV-specific CD8+ T-cell VIA at baseline. Importantly, VIA levels correlated with the magnitude of the anti-Gag cellular response. The advantage of Gag-specific cells may result from their enhanced ability to mediate lysis of infected cells (evidenced by a higher capacity to degranulate and to mediate VIA) and to simultaneously produce IFN-γ. Finally, Gag immunodominance was associated with elevated plasma levels of interleukin 2 (IL-2) and macrophage inflammatory protein 1β (MIP-1β). All together, this study underscores the importance of CD8+ T-cell specificity in the improved control of disease progression, which was related to the capacity of Gag-specific cells to mediate both lytic and nonlytic antiviral mechanisms at early time points postinfection. PMID:23616666

Systemic Inflammatory Response Syndrome After Major Abdominal Surgery Predicted by Early Upregulation of TLR4 and TLR5.

PubMed

Lahiri, Rajiv; Derwa, Yannick; Bashir, Zora; Giles, Edward; Torrance, Hew D T; Owen, Helen C; O'Dwyer, Michael J; O'Brien, Alastair; Stagg, Andrew J; Bhattacharya, Satyajit; Foster, Graham R; Alazawi, William

2016-05-01

To study innate immune pathways in patients undergoing hepatopancreaticobiliary surgery to understand mechanisms leading to enhanced inflammatory responses and identifying biomarkers of adverse clinical consequences. Patients undergoing major abdominal surgery are at risk of life-threatening systemic inflammatory response syndrome (SIRS) and sepsis. Early identification of at-risk patients would allow tailored postoperative care and improve survival. Two separate cohorts of patients undergoing major hepatopancreaticobiliary surgery were studied (combined n = 69). Bloods were taken preoperatively, on day 1 and day 2 postoperatively. Peripheral blood mononuclear cells and serum were separated and immune phenotype and function assessed ex vivo. Early innate immune dysfunction was evident in 12 patients who subsequently developed SIRS (postoperative day 6) compared with 27 who did not, when no clinical evidence of SIRS was apparent (preoperatively or days 1 and 2). Serum interleukin (IL)-6 concentration and monocyte Toll-like receptor (TLR)/NF-κB/IL-6 functional pathways were significantly upregulated and overactive in patients who developed SIRS (P < 0.0001). Interferon α-mediated STAT1 phosphorylation was higher preoperatively in patients who developed SIRS. Increased TLR4 and TLR5 gene expression in whole blood was demonstrated in a separate validation cohort of 30 patients undergoing similar surgery. Expression of TLR4/5 on monocytes, particularly intermediate CD14CD16 monocytes, on day 1 or 2 predicted SIRS with accuracy 0.89 to 1.0 (areas under receiver operator curves). These data demonstrate the mechanism for IL-6 overproduction in patients who develop postoperative SIRS and identify markers that predict patients at risk of SIRS 5 days before the onset of clinical signs.

Elucidating the mechanisms linking early pubertal timing, sexual activity, and substance use for maltreated versus nonmaltreated adolescents

PubMed Central

Negriff, Sonya; Brensilver, Matthew; Trickett, Penelope K.

2015-01-01

Purpose To test models linking pubertal timing, peer substance use, sexual behavior, and substance use for maltreated versus comparison adolescents. Three theoretical mechanisms were tested: 1) peer influence links early pubertal timing to later sexual behavior and substance use, 2) early maturers engage in substance use on their own and then select substance-using friends, or 3) early maturers initiate sexual behaviors which leads them to substance-using peers. Methods The data came from a longitudinal study of the effects of child maltreatment on adolescent development (303 maltreated and 151 comparison adolescents; age: 9–13 years at initial wave). Multiple-group structural equation models tested the hypotheses across three timepoints including variables of pubertal timing, perception of peer substance use, sexual behavior, and self-reported substance use. Results Early pubertal timing was associated with substance-using peers only for maltreated adolescents, indicating the mediation path from early pubertal timing through substance-using peers to subsequent adolescent substance use and sexual behavior only holds for maltreated adolescents. Mediation via sexual behavior was significant for both maltreated and comparison adolescents. This indicates that sexual behavior may be a more universal mechanism linking early maturation with risky friends regardless of adverse life experiences. Conclusions The findings are a step toward elucidating the developmental pathways from early puberty to risk behavior and identifying early experiences that may alter mediation effects. PMID:26003577

Comparison of the Mechanical Properties of Early Leukocyte- and Platelet-Rich Fibrin versus PRGF/Endoret Membranes.

PubMed

Khorshidi, Hooman; Raoofi, Saeed; Bagheri, Rafat; Banihashemi, Hodasadat

2016-01-01

Objectives. The mechanical properties of membranes are important factors in the success of treatment and clinical handling. The goal of this study was to compare the mechanical properties of early leukocyte- and platelet-rich fibrin (L-PRF) versus PRGF/Endoret membrane. Materials and Methods. In this experimental study, membranes were obtained from 10 healthy male volunteers. After obtaining 20 cc venous blood from each volunteer, 10 cc was used to prepare early L-PRF (group 1) and the rest was used to get a membrane by PRGF-Endoret system (group 2). Tensile loads were applied to specimens using universal testing machine. Tensile strength, stiffness, and toughness of the two groups of membranes were calculated and compared by paired t-test. Results. The mean tensile strength and toughness were higher in group 1 with a significant difference (P < 0.05). The mean stiffness in group 1 was also higher but not statistically significant (P > 0.05). Conclusions. The results showed that early L-PRF membranes had stronger mechanical properties than membranes produced by PRGF-Endoret system. Early L-PRF membranes might have easier clinical handling and could be a more proper scaffold in periodontal regenerative procedures. The real results of the current L-PRF should be in fact much higher than what is reported here.

Comparison of the Mechanical Properties of Early Leukocyte- and Platelet-Rich Fibrin versus PRGF/Endoret Membranes

PubMed Central

Khorshidi, Hooman; Raoofi, Saeed; Bagheri, Rafat; Banihashemi, Hodasadat

2016-01-01

Objectives. The mechanical properties of membranes are important factors in the success of treatment and clinical handling. The goal of this study was to compare the mechanical properties of early leukocyte- and platelet-rich fibrin (L-PRF) versus PRGF/Endoret membrane. Materials and Methods. In this experimental study, membranes were obtained from 10 healthy male volunteers. After obtaining 20 cc venous blood from each volunteer, 10 cc was used to prepare early L-PRF (group 1) and the rest was used to get a membrane by PRGF-Endoret system (group 2). Tensile loads were applied to specimens using universal testing machine. Tensile strength, stiffness, and toughness of the two groups of membranes were calculated and compared by paired t-test. Results. The mean tensile strength and toughness were higher in group 1 with a significant difference (P < 0.05). The mean stiffness in group 1 was also higher but not statistically significant (P > 0.05). Conclusions. The results showed that early L-PRF membranes had stronger mechanical properties than membranes produced by PRGF-Endoret system. Early L-PRF membranes might have easier clinical handling and could be a more proper scaffold in periodontal regenerative procedures. The real results of the current L-PRF should be in fact much higher than what is reported here. PMID:26880919

Vascular-mediated signalling involved in early phosphate stress response in plants.

PubMed

Zhang, Zhaoliang; Zheng, Yi; Ham, Byung-Kook; Chen, Jieyu; Yoshida, Akiko; Kochian, Leon V; Fei, Zhangjun; Lucas, William J

2016-04-04

Depletion of finite global rock phosphate (Pi) reserves will impose major limitations on future agricultural productivity and food security. Hence, modern breeding programmes seek to develop Pi-efficient crops with sustainable yields under reduced Pi fertilizer inputs. In this regard, although the long-term responses of plants to Pi stress are well documented, the early signalling events have yet to be elucidated. Here, we show plant tissue-specific responses to early Pi stress at the transcription level and a predominant role of the plant vascular system in this process. Specifically, imposition of Pi stress induces rapid and major changes in the mRNA population in the phloem translocation stream, and grafting studies have revealed that many hundreds of phloem-mobile mRNAs are delivered to specific sink tissues. We propose that the shoot vascular system acts as the site of root-derived Pi stress perception, and the phloem serves to deliver a cascade of signals to various sinks, presumably to coordinate whole-plant Pi homeostasis.

Extracorporeal Shock Wave Therapy Suppresses the Early Proinflammatory Immune Response to a Severe Cutaneous Burn Injury

DTIC Science & Technology

2009-02-01

Burn wound model Mice were anaesthetised using isoflurane inha- lation. After shaving the dorsum, the exposed skin was washed gently with room...Extracorporeal shock wave therapy suppresses the early proinflammatory immune response to a severe cutaneous burn injury* Thomas A Davis, Alexander...S, Peoples GE, Tadaki D, Elster EA. Extracorporeal shock wave therapy suppresses the early proinflammatory immune response to a severe cutaneous burn

Perceived early-life maternal care and the cortisol response to repeated psychosocial stress

PubMed Central

Engert, Veronika; Efanov, Simona I.; Dedovic, Katarina; Duchesne, Annie; Dagher, Alain; Pruessner, Jens C.

2010-01-01

Background In the past decade, a body of animal and human research has revealed a profound influence of early-life experiences, ranging from variations in parenting behaviour to severe adversity, on hypothalamic–pituitary–adrenal axis regulation in adulthood. In our own previous studies, we have shown how variations in early-life parental care influence the development of the hippocampus and modify the cortisol awakening response. Methods In the present study, we investigated the influence of early-life maternal care on cortisol, heart rate and subjective psychological responses to the repeated administration of a psychosocial laboratory stressor in a population of 63 healthy young adults. Low, medium and high early-life maternal care groups were identified using the Parental Bonding Instrument. Results Controlling for the effect of sex, we found an inverted u-shaped relation between increasing levels of maternal care and cortisol stress responsivity. Specifically, overall and stress-induced cortisol levels went from below normal in the low maternal care, to normal in the medium care, back to below normal in the high maternal care groups. We found no group differences with respect to heart rate and subjective psychological stress measures. Whereas low and high maternal care groups exhibited similarly low endocrine stress responses, their psychological profiles were opposed with increased levels of depression and anxiety and decreased self-esteem in the low care group. Limitations Sex was unequally distributed among maternal care groups, whereby the number of men with low maternal care was too small to allow introducing sex as a second between-group variable. Conclusion We discuss the potential significance of this dissociation between endocrine and psychological parameters with respect to stress vulnerability and resistance for each maternal care group. PMID:20964960

Transient early neurotrophin release and delayed inflammatory cytokine release by microglia in response to PAR-2 stimulation

PubMed Central

2012-01-01

Activated microglia exerts both beneficial and deleterious effects on neurons, but the signaling mechanism controlling these distinct responses remain unclear. We demonstrated that treatment of microglial cultures with the PAR-2 agonist, 2-Furoyl-LIGRLO-NH2, evoked early transient release of BDNF, while sustained PAR-2 stimulation evoked the delayed release of inflammatory cytokines (IL-1β and TNF-α) and nitric oxide. Culture medium harvested during the early phase (at 1 h) of microglial activation induced by 2-Furoyl-LIGRLO-NH2 (microglial conditioned medium, MCM) had no deleterious effects on cultured neurons, while MCM harvested during the late phase (at 72 h) promoted DNA fragmentation and apoptosis as indicated by TUNEL and annexin/PI staining. Blockade of PAR-1 during the early phase of PAR-2 stimulation enhanced BDNF release (by 11%, small but significant) while a PAR-1 agonist added during the late phase (24 h after 2-Furoyl-LIGRLO-NH2 addition) suppressed the release of cytokines and NO. The neuroprotective and neurotoxic effects of activated microglial exhibit distinct temporal profiles that are regulated by PAR-1 and PAR-2 stimulation. It may be possible to facilitate neuronal recovery and repair by appropriately timed stimulation and inhibition of microglial PAR-1 and PAR-2 receptors. PMID:22731117

Transient early neurotrophin release and delayed inflammatory cytokine release by microglia in response to PAR-2 stimulation.

PubMed

Chen, Chen-Wen; Chen, Qian-Bo; Ouyang, Qing; Sun, Ji-Hu; Liu, Fang-Ting; Song, Dian-Wen; Yuan, Hong-Bin

2012-06-25

Activated microglia exerts both beneficial and deleterious effects on neurons, but the signaling mechanism controlling these distinct responses remain unclear. We demonstrated that treatment of microglial cultures with the PAR-2 agonist, 2-Furoyl-LIGRLO-NH2, evoked early transient release of BDNF, while sustained PAR-2 stimulation evoked the delayed release of inflammatory cytokines (IL-1 β and TNF-α) and nitric oxide. Culture medium harvested during the early phase (at 1 h) of microglial activation induced by 2-Furoyl-LIGRLO-NH2 (microglial conditioned medium, MCM) had no deleterious effects on cultured neurons, while MCM harvested during the late phase (at 72 h) promoted DNA fragmentation and apoptosis as indicated by TUNEL and annexin/PI staining. Blockade of PAR-1 during the early phase of PAR-2 stimulation enhanced BDNF release (by 11%, small but significant) while a PAR-1 agonist added during the late phase (24 h after 2-Furoyl-LIGRLO-NH2 addition) suppressed the release of cytokines and NO. The neuroprotective and neurotoxic effects of activated microglial exhibit distinct temporal profiles that are regulated by PAR-1 and PAR-2 stimulation. It may be possible to facilitate neuronal recovery and repair by appropriately timed stimulation and inhibition of microglial PAR-1 and PAR-2 receptors.

Difference between electrostriction kinetics, and mechanical response of segmented polyurethane-based EAP

NASA Astrophysics Data System (ADS)

Jomaa, M. H.; Seveyrat, L.; Perrin, V.; Lebrun, L.; Masenelli-Varlot, K.; Diguet, Gildas; Cavaille, J. Y.

2017-03-01

Among the key parameters, which must be taken into account for the choice of actuators used as electrical to mechanical energy converters, the response to a step function and/or the frequency dependence of this response is extremely important. For polymeric actuators and more generally for electroactive polymers, three mechanisms can be at the origin of energy losses, namely dielectric relaxations, viscoelastic relaxations and possible electrical conductivity. In a previous paper, we studied the electrical behavior of segmented polyurethanes with different weight fractions of hard (MDI-BDO) and soft (PTMO) segments. They were shown to exhibit three main mechanisms, namely, from the fastest to the slowest, a secondary or β-relaxation, the main or α-relaxation associated with the glass-rubber transition of the soft phase, and finally, their electrical conductivity. In the present work, we present the general viscoelastic response (as measured through mechanical spectrometry) of the same polyurethanes and their respective time dependent electrostriction responses, and compare it with the relaxation characteristic times of electrical and mechanical spectroscopy data.

Neuro-Immune Mechanisms in Response to Venezuelan Equine Encephalitis Virus Infection

DTIC Science & Technology

2000-01-01

iii ABSTRACT NEURO-IMMUNE MECHANISMS IN RESPONSE TO VENEZUELAN EQUINE ENCEPHALITIS VIRUS INFECTION Major Bruce A. Schoneboom directed by Franziska B...Grieder, DVM, Ph.D., Assistant Professor of Microbiology and Immunology, Molecular and Cellular Biology, and Neuroscience Venezuelan equine ...3. DATES COVERED - 4. TITLE AND SUBTITLE NEURO-IMMUNE MECHANISMS IN RESPONSE TO VENEZUELAN EQUINE ENCEPHALITIS VIRUS INFECTION 5a. CONTRACT

[Aging affects early stage direction selectivity of MT cells in rhesus monkeys].

PubMed

Liang, Zhen; Chen, Yue-Ming; Meng, Xue; Wang, Yi; Zhou, Bao-Zhuo; Xie, Ying-Ying; He, Wen-Sheng

2012-10-01

The middle temporal area (MT/V5) plays an important role in motion processing. Neurons in this area have a strongly selective response to the moving direction of objects and as such, the selectivity of MT neurons was proposed to be a neural mechanism for the perception of motion. Our previous studies have found degradation in direction selectivity of MT neurons in old monkeys, but this direction selectivity was calculated during the whole response time and the results were not able to uncover the mechanism of motion perception over a time course. Furthermore, experiments have found that direction selectivity was enhanced by attention at a later stage. Therefore, the response should be excluded in experiments with anesthesia. To further characterize the neural mechanism over a time course, we investigated the age-related changes of direction selectivity in the early stage by comparing the proportions of direction selective MT cells in old and young macaque monkeys using in vivo single-cell recording techniques. Our results show that the proportion of early-stage-direction-selective cells is lower in old monkeys than in young monkeys, and that the early stage direction bias (esDB) of old MT cells decreased relative to young MT cells. Furthermore, the proportion of MT cells having strong early stage direction selectivity in old monkeys was decreased. Accordingly, the functional degradation in the early stage of MT cells may mediate perceptual declines of old primates in visual motion tasks.

Early immune responses are independent of RGC dysfunction in glaucoma with complement component C3 being protective.

PubMed

Harder, Jeffrey M; Braine, Catherine E; Williams, Pete A; Zhu, Xianjun; MacNicoll, Katharine H; Sousa, Gregory L; Buchanan, Rebecca A; Smith, Richard S; Libby, Richard T; Howell, Gareth R; John, Simon W M

2017-05-09

Various immune response pathways are altered during early, predegenerative stages of glaucoma; however, whether the early immune responses occur secondarily to or independently of neuronal dysfunction is unclear. To investigate this relationship, we used the Wld s allele, which protects from axon dysfunction. We demonstrate that DBA/2J .Wld s mice develop high intraocular pressure (IOP) but are protected from retinal ganglion cell (RGC) dysfunction and neuroglial changes that otherwise occur early in DBA/2J glaucoma. Despite this, immune pathways are still altered in DBA/2J .Wld s mice. This suggests that immune changes are not secondary to RGC dysfunction or altered neuroglial interactions, but may be directly induced by the increased strain imposed by high IOP. One early immune response following IOP elevation is up-regulation of complement C3 in astrocytes of DBA/2J and DBA/2J. Wld s mice. Unexpectedly, because the disruption of other complement components, such as C1Q, is protective in glaucoma, C3 deficiency significantly increased the number of DBA/2J eyes with nerve damage and RGC loss at an early time point after IOP elevation. Transcriptional profiling of C3-deficient cultured astrocytes implicated EGFR signaling as a hub in C3-dependent responses. Treatment with AG1478, an EGFR inhibitor, also significantly increased the number of DBA/2J eyes with glaucoma at the same early time point. These findings suggest that C3 protects from early glaucomatous damage, a process that may involve EGFR signaling and other immune responses in the optic nerve head. Therefore, therapies that target specific components of the complement cascade, rather than global inhibition, may be more applicable for treating human glaucoma.

Early immune responses are independent of RGC dysfunction in glaucoma with complement component C3 being protective

PubMed Central

Harder, Jeffrey M.; Braine, Catherine E.; Williams, Pete A.; Zhu, Xianjun; MacNicoll, Katharine H.; Sousa, Gregory L.; Buchanan, Rebecca A.; Smith, Richard S.; Howell, Gareth R.; John, Simon W. M.

2017-01-01

Various immune response pathways are altered during early, predegenerative stages of glaucoma; however, whether the early immune responses occur secondarily to or independently of neuronal dysfunction is unclear. To investigate this relationship, we used the Wlds allele, which protects from axon dysfunction. We demonstrate that DBA/2J.Wlds mice develop high intraocular pressure (IOP) but are protected from retinal ganglion cell (RGC) dysfunction and neuroglial changes that otherwise occur early in DBA/2J glaucoma. Despite this, immune pathways are still altered in DBA/2J.Wlds mice. This suggests that immune changes are not secondary to RGC dysfunction or altered neuroglial interactions, but may be directly induced by the increased strain imposed by high IOP. One early immune response following IOP elevation is up-regulation of complement C3 in astrocytes of DBA/2J and DBA/2J.Wlds mice. Unexpectedly, because the disruption of other complement components, such as C1Q, is protective in glaucoma, C3 deficiency significantly increased the number of DBA/2J eyes with nerve damage and RGC loss at an early time point after IOP elevation. Transcriptional profiling of C3-deficient cultured astrocytes implicated EGFR signaling as a hub in C3-dependent responses. Treatment with AG1478, an EGFR inhibitor, also significantly increased the number of DBA/2J eyes with glaucoma at the same early time point. These findings suggest that C3 protects from early glaucomatous damage, a process that may involve EGFR signaling and other immune responses in the optic nerve head. Therefore, therapies that target specific components of the complement cascade, rather than global inhibition, may be more applicable for treating human glaucoma. PMID:28446616

Early-Life Nutritional Programming of Cognition-The Fundamental Role of Epigenetic Mechanisms in Mediating the Relation between Early-Life Environment and Learning and Memory Process.

PubMed

Moody, Laura; Chen, Hong; Pan, Yuan-Xiang

2017-03-01

The perinatal period is a window of heightened plasticity that lays the groundwork for future anatomic, physiologic, and behavioral outcomes. During this time, maternal diet plays a pivotal role in the maturation of vital organs and the establishment of neuronal connections. However, when perinatal nutrition is either lacking in specific micro- and macronutrients or overloaded with excess calories, the consequences can be devastating and long lasting. The brain is particularly sensitive to perinatal insults, with several neurologic and psychiatric disorders having been linked to a poor in utero environment. Diseases characterized by learning and memory impairments, such as autism, schizophrenia, and Alzheimer disease, are hypothesized to be attributed in part to environmental factors, and evidence suggests that the etiology of these conditions may date back to very early life. In this review, we discuss the role of the early-life diet in shaping cognitive outcomes in offspring. We explore the endocrine and immune mechanisms responsible for these phenotypes and discuss how these systemic factors converge to change the brain's epigenetic landscape and regulate learning and memory across the lifespan. Through understanding the maternal programming of cognition, critical steps may be taken toward preventing and treating diseases that compromise learning and memory. © 2017 American Society for Nutrition.

Early Caffeine and Weaning from Mechanical Ventilation in Preterm Infants: A Randomized, Placebo-Controlled Trial.

PubMed

Amaro, Cynthia M; Bello, Jose A; Jain, Deepak; Ramnath, Alexandra; D'Ugard, Carmen; Vanbuskirk, Silvia; Bancalari, Eduardo; Claure, Nelson

2018-05-01

To evaluate in a randomized, double-blind, placebo-controlled trial the effect of early caffeine on the age of first successful extubation in preterm infants. Preterm infants born at 23-30 weeks of gestation requiring mechanical ventilation in the first 5 postnatal days were randomized to receive a 20 mg/kg loading dose followed by 5 mg/kg/day of caffeine or placebo until considered ready for extubation. The placebo group received a blinded loading dose of caffeine before extubation. Infants were randomized to receive caffeine (n = 41) or placebo (n = 42). Age at first successful extubation did not differ between early caffeine (median, 24 days; IQR, 10-41 days) and control groups (median, 20 days; IQR, 9-43 days; P = .7). An interim analysis at 75% enrollment showed a trend toward higher mortality in 1 of the groups and the data safety and monitoring board recommended stopping the trial. Unblinded analysis revealed mortality did not differ significantly between the early caffeine (9 [22%]) and control groups (5 [12%]; P = .22). Early initiation of caffeine in this group of premature infants did not reduce the age of first successful extubation. A nonsignificant trend toward higher mortality in the early caffeine group led to a cautious decision to stop the trial. These findings suggest caution with early use of caffeine in mechanically ventilated preterm infants until more efficacy and safety data become available. ClinicalTrials.gov: NCT01751724. Copyright © 2018 Elsevier Inc. All rights reserved.

Augmentation of sensory-evoked hemodynamic response in an early Alzheimer's disease mouse model.

PubMed

Kim, Jinho; Jeong, Yong

2013-01-01

Based on enlarged blood oxygen level-dependent (BOLD) responses in cognitively normal subjects at risk for Alzheimer's disease (AD), compensatory neuronal hyperactivation has been proposed as an early marker for diagnosis of AD. The BOLD response results from neurovascular coupling, i.e., hemodynamic response induced by neuronal activity. However, there has been no evidence of task-induced increases in hemodynamic response in animal models of AD. Here, we observed an augmented hemodynamic response pattern in a transgenic AβPP(SWE)/PS1ΔE9 mouse model of AD using three in vivo imaging methods: intrinsic optical signal imaging, multi-photon laser scanning microscopy, and laser Doppler flowmetry. Sensory stimulation resulted in augmented and prolonged hemodynamic responses in transgenic mice evidenced by changes in total, oxygenated, and deoxygenated hemoglobin concentration. This difference between transgenic and wild-type mice was significant at 7 months of age when amyloid plaques and cerebral amyloid angiopathy had developed but not at younger or older ages. Correspondingly, sensory stimulation-induced pial arteriole diameter was also augmented and prolonged in transgenic mice at 7 months of age. Cerebral blood flow response in transgenic mice was augmented but not prolonged. These results are consistent with the existence of BOLD signal hyperactivation in non-demented AD-risk human subjects, supporting its potential use as an early diagnostic marker of AD.

The initial repair response of articular cartilage after mechanically induced damage.

PubMed

van Haaften, Eline E; Ito, Keita; van Donkelaar, Corrinus C

2017-06-01

The regenerative potential of articular cartilage (AC) defects is limited and depends on defect size, biomechanical conditions, and age. Early events after overloading might be predictive for cartilage degeneration in the long term. Therefore, the present aim is to investigate the temporal response of cartilage to overloading at cell, matrix, and tissue level during the first period after mechanical overloading. In the present study, the effect of high loading (∼8 MPa) at a high rate (∼14 MPa/s) at day 0 during a 9 day period on collagen damage, gene expression, cell death, and biochemical composition in AC was investigated. A model system was developed which enabled culturing osteochondral explants after loading. Proteoglycan content was repeatedly monitored over time using μCT, whereas other evaluations required destructive measurements. Changes in matrix related gene expressions indicated a degenerative response during the first 6 h after loading. After 24 h, this was restored and data suggested an initial repair response. Cell death and microscopic damage increased after 24 h following loading. These degradative changes were not restored within the 9 day culture period, and were accompanied by a slight loss of proteoglycans at the articular surface that extended into the middle zones. The combined findings indicate that high magnitude loading of articular cartilage at a high rate induces an initial damage that later initiates a healing response that can probably not be retained due to loss of cell viability. Consequently, the matrix cannot be restored in the short term. © 2016 Orthopaedic Research Society. Published by Wiley Periodicals, Inc. J Orthop Res 35:1265-1273, 2017. © 2016 Orthopaedic Research Society. Published by Wiley Periodicals, Inc.

Population Response Profiles in Early Visual Cortex Are Biased in Favor of More Valuable Stimuli

PubMed Central

Saproo, Sameer

2010-01-01

Voluntary and stimulus-driven shifts of attention can modulate the representation of behaviorally relevant stimuli in early areas of visual cortex. In turn, attended items are processed faster and more accurately, facilitating the selection of appropriate behavioral responses. Information processing is also strongly influenced by past experience and recent studies indicate that the learned value of a stimulus can influence relatively late stages of decision making such as the process of selecting a motor response. However, the learned value of a stimulus can also influence the magnitude of cortical responses in early sensory areas such as V1 and S1. These early effects of stimulus value are presumed to improve the quality of sensory representations; however, the nature of these modulations is not clear. They could reflect nonspecific changes in response amplitude associated with changes in general arousal or they could reflect a bias in population responses so that high-value features are represented more robustly. To examine this issue, subjects performed a two-alternative forced choice paradigm with a variable-interval payoff schedule to dynamically manipulate the relative value of two stimuli defined by their orientation (one was rotated clockwise from vertical, the other counterclockwise). Activation levels in visual cortex were monitored using functional MRI and feature-selective voxel tuning functions while subjects performed the behavioral task. The results suggest that value not only modulates the relative amplitude of responses in early areas of human visual cortex, but also sharpens the response profile across the populations of feature-selective neurons that encode the critical stimulus feature (orientation). Moreover, changes in space- or feature-based attention cannot easily explain the results because representations of both the selected and the unselected stimuli underwent a similar feature-selective modulation. This sharpening in the population

Adenovirus Core Protein VII Protects the Viral Genome from a DNA Damage Response at Early Times after Infection▿

PubMed Central

Karen, Kasey A.; Hearing, Patrick

2011-01-01

Adenovirus has a linear, double-stranded DNA genome that is perceived by the cellular Mre11-Rad50-Nbs1 (MRN) DNA repair complex as a double-strand break. If unabated, MRN elicits a double-strand break repair response that blocks viral DNA replication and ligates the viral genomes into concatemers. There are two sets of early viral proteins that inhibit the MRN complex. The E1B-55K/E4-ORF6 complex recruits an E3 ubiquitin ligase and targets MRN proteins for proteasome-dependent degradation. The E4-ORF3 protein inhibits MRN through sequestration. The mechanism that prevents MRN recognition of the viral genome prior to the expression of these early proteins was previously unknown. Here we show a temporal correlation between the loss of viral core protein VII from the adenovirus genome and a gain of checkpoint signaling due to the double-strand break repair response. While checkpoint signaling corresponds to the recognition of the viral genome, core protein VII binding to and checkpoint signaling at viral genomes are largely mutually exclusive. Transcription is known to release protein VII from the genome, and the inhibition of transcription shows a decrease in checkpoint signaling. Finally, we show that the nuclease activity of Mre11 is dispensable for the inhibition of viral DNA replication during a DNA damage response. These results support a model involving the protection of the incoming viral genome from checkpoint signaling by core protein VII and suggest that the induction of an MRN-dependent DNA damage response may inhibit adenovirus replication by physically masking the origins of DNA replication rather than altering their integrity. PMID:21345950

Integrated Stress Response Mediates Epithelial Injury in Mechanical Ventilation.

PubMed

Dolinay, Tamas; Himes, Blanca E; Shumyatcher, Maya; Lawrence, Gladys Gray; Margulies, Susan S

2017-08-01

Ventilator-induced lung injury (VILI) is a severe complication of mechanical ventilation that can lead to acute respiratory distress syndrome. VILI is characterized by damage to the epithelial barrier with subsequent pulmonary edema and profound hypoxia. Available lung-protective ventilator strategies offer only a modest benefit in preventing VILI because they cannot impede alveolar overdistension and concomitant epithelial barrier dysfunction in the inflamed lung regions. There are currently no effective biochemical therapies to mitigate injury to the alveolar epithelium. We hypothesize that alveolar stretch activates the integrated stress response (ISR) pathway and that the chemical inhibition of this pathway mitigates alveolar barrier disruption during stretch and mechanical ventilation. Using our established rat primary type I-like alveolar epithelial cell monolayer stretch model and in vivo rat mechanical ventilation that mimics the alveolar overdistension seen in acute respiratory distress syndrome, we studied epithelial responses to mechanical stress. Our studies revealed that the ISR signaling pathway is a key modulator of epithelial permeability. We show that prolonged epithelial stretch and injurious mechanical ventilation activate the ISR, leading to increased alveolar permeability, cell death, and proinflammatory signaling. Chemical inhibition of protein kinase RNA-like endoplasmic reticulum kinase, an upstream regulator of the pathway, resulted in decreased injury signaling and improved barrier function after prolonged cyclic stretch and injurious mechanical ventilation. Our results provide new evidence that therapeutic targeting of the ISR can mitigate VILI.

Early versus later response to treatment in patients with community-acquired pneumonia: analysis of the REACH study.

PubMed

Blasi, Francesco; Ostermann, Helmut; Racketa, Jill; Medina, Jesús; McBride, Kyle; Garau, Javier

2014-01-22

Key goals in the treatment of CAP include early response to treatment and achievement of clinical stability. The US FDA recommends early response endpoints (72 hours after initiation of treatment) in clinical trials for the treatment of community-acquired bacterial pneumonia. REACH (REtrospective Study to Assess the Clinical Management of Patients With Moderate-to-Severe Complicated Skin and Soft Tissue Infections [cSSTI] or CAP in the Hospital Setting) was a retrospective observational study, providing current data on the clinical management and resource burden of CAP in real-life settings in European hospitals. This analysis reviews the characteristics and outcomes of patients showing early positive response to treatment (time to clinical stability [TCS] ≤4 days, as assessed by Halm's criteria) compared with patients with later positive response (TCS >4 days). Patients were adults, hospitalized with CAP (2010-2011) and requiring in-hospital treatment with intravenous antibiotics. Of the 2039 patients included in REACH, 585 (28.7%) had TCS assessed by Halm's criteria: 332 (56.8%) showed early response (median 3.0 days), and 253 (43.2%) showed later response to treatment (median 7.0 days). Use of Halm's criteria varied across participating countries, ranging from 0% (Belgium) to 49.1% (UK). Patient characteristics and relevant medical history were similar between the two groups. There were no notable differences in initial antibiotic therapy between groups, except that more early responders had been treated with amoxicillin-clavulanate and amoxicillin monotherapy (22.6%; 7.5%, respectively) than later responders (5.9%; 1.2%, respectively). Initial treatment modification and re-infection or recurrences were less frequent in early responders compared with later responders (14.2% and 3.3% vs. 34.8% and 5.9%, respectively). Early responders had a shorter duration of hospitalization (mean 9.4 ± SD 7.0; median 8.0 days vs. mean 15.6 ± SD 10.5; median 12

Early-life risperidone enhances locomotor responses to amphetamine during adulthood.

PubMed

Lee Stubbeman, Bobbie; Brown, Clifford J; Yates, Justin R; Bardgett, Mark E

2017-10-05

Antipsychotic drug prescriptions for pediatric populations have increased over the past 20 years, particularly the use of atypical antipsychotic drugs such as risperidone. Most antipsychotic drugs target forebrain dopamine systems, and early-life antipsychotic drug exposure could conceivably reset forebrain neurotransmitter function in a permanent manner that persists into adulthood. This study determined whether chronic risperidone administration during development modified locomotor responses to the dopamine/norepinephrine agonist, D-amphetamine, in adult rats. Thirty-five male Long-Evans rats received an injection of one of four doses of risperidone (vehicle, .3, 1.0, 3.0mg/kg) each day from postnatal day 14 through 42. Locomotor activity was measured for 1h on postnatal days 46 and 47, and then for 24h once a week over the next two weeks. Beginning on postnatal day 75, rats received one of four doses of amphetamine (saline, .3, 1.0, 3.0mg/kg) once a week for four weeks. Locomotor activity was measured for 27h after amphetamine injection. Rats administered risperidone early in life demonstrated increased activity during the 1 and 24h test sessions conducted prior to postnatal day 75. Taking into account baseline group differences, these same rats exhibited significantly more locomotor activity in response to the moderate dose of amphetamine relative to controls. These results suggest that early-life treatment with atypical antipsychotic drugs, like risperidone, permanently alters forebrain catecholamine function and increases sensitivity to drugs that target such function. Copyright © 2017 Elsevier B.V. All rights reserved.

Impaired early visual response modulations to spatial information in chronic schizophrenia

PubMed Central

Knebel, Jean-François; Javitt, Daniel C.; Murray, Micah M.

2011-01-01

Early visual processing stages have been demonstrated to be impaired in schizophrenia patients and their first-degree relatives. The amplitude and topography of the P1 component of the visual evoked potential (VEP) are both affected; the latter of which indicates alterations in active brain networks between populations. At least two issues remain unresolved. First, the specificity of this deficit (and suitability as an endophenotype) has yet to be established, with evidence for impaired P1 responses in other clinical populations. Second, it remains unknown whether schizophrenia patients exhibit intact functional modulation of the P1 VEP component; an aspect that may assist in distinguishing effects specific to schizophrenia. We applied electrical neuroimaging analyses to VEPs from chronic schizophrenia patients and healthy controls in response to variation in the parafoveal spatial extent of stimuli. Healthy controls demonstrated robust modulation of the VEP strength and topography as a function of the spatial extent of stimuli during the P1 component. By contrast, no such modulations were evident at early latencies in the responses from patients with schizophrenia. Source estimations localized these deficits to the left precuneus and medial inferior parietal cortex. These findings provide insights on potential underlying low-level impairments in schizophrenia. PMID:21764264

Telomere lengthening early in development.

PubMed

Liu, Lin; Bailey, Susan M; Okuka, Maja; Muñoz, Purificación; Li, Chao; Zhou, Lingjun; Wu, Chao; Czerwiec, Eva; Sandler, Laurel; Seyfang, Andreas; Blasco, Maria A; Keefe, David L

2007-12-01

Stem cells and cancer cells maintain telomere length mostly through telomerase. Telomerase activity is high in male germ line and stem cells, but is low or absent in mature oocytes and cleavage stage embryos, and then high again in blastocysts. How early embryos reset telomere length remains poorly understood. Here, we show that oocytes actually have shorter telomeres than somatic cells, but their telomeres lengthen remarkably during early cleavage development. Moreover, parthenogenetically activated oocytes also lengthen their telomeres, thus the capacity to elongate telomeres must reside within oocytes themselves. Notably, telomeres also elongate in the early cleavage embryos of telomerase-null mice, demonstrating that telomerase is unlikely to be responsible for the abrupt lengthening of telomeres in these cells. Coincident with telomere lengthening, extensive telomere sister-chromatid exchange (T-SCE) and colocalization of the DNA recombination proteins Rad50 and TRF1 were observed in early cleavage embryos. Both T-SCE and DNA recombination proteins decrease in blastocyst stage embryos, whereas telomerase activity increases and telomeres elongate only slowly. We suggest that telomeres lengthen during the early cleavage cycles following fertilization through a recombination-based mechanism, and that from the blastocyst stage onwards, telomerase only maintains the telomere length established by this alternative mechanism.

Multidecadal response of naturally regenerated southern pine to early competition control and commercial thinning

Treesearch

Andrew S. Nelson; Don C. Bragg

2016-01-01

Multidecadal responses to early competition control are poorly documented in naturally regenerated southern pine stands. This study examined the effects of the following early herbicide treatments in thinned southern pine stands through age 31: (1) no control (CK), (2) herbaceous vegetation control only (HC), (3) woody vegetation control only (WC), and (4) total (woody...

Elucidating the mechanisms linking early pubertal timing, sexual activity, and substance use for maltreated versus nonmaltreated adolescents.

PubMed

Negriff, Sonya; Brensilver, Matthew; Trickett, Penelope K

2015-06-01

To test models linking pubertal timing, peer substance use, sexual behavior, and substance use for maltreated versus comparison adolescents. Three theoretical mechanisms were tested: (1) peer influence links early pubertal timing to later sexual behavior and substance use; (2) early maturers engage in substance use on their own and then select substance-using friends; or (3) early maturers initiate sexual behaviors which lead them to substance-using peers. The data came from a longitudinal study of the effects of child maltreatment on adolescent development (303 maltreated and 151 comparison adolescents; age, 9-13 years at initial wave). Multiple-group structural equation models tested the hypotheses across three time points including variables of pubertal timing, perception of peer substance use, sexual behavior, and self-reported substance use. Early pubertal timing was associated with substance-using peers only for maltreated adolescents, indicating the mediation path from early pubertal timing through substance-using peers to subsequent adolescent substance use and sexual behavior only holds for maltreated adolescents. Mediation via sexual behavior was significant for both maltreated and comparison adolescents. This indicates that sexual behavior may be a more universal mechanism linking early maturation with risky friends regardless of adverse life experiences. The findings are a step toward elucidating the developmental pathways from early puberty to risk behavior and identifying early experiences that may alter mediation effects. Copyright © 2015 Society for Adolescent Health and Medicine. Published by Elsevier Inc. All rights reserved.

The Cytoskeleton and Force Response Mechanisms

NASA Technical Reports Server (NTRS)

Allen, Philip Goodwin

2003-01-01

The long term aim of this project was to define the mechanisms by which cells sense and respond to the physical forces experienced at 1g and missing in microgravity. Identification and characterization of the elements of the cells force response mechanism could provide pathways and molecules to serve as targets for pharmacological intervention to mitigate the pathologic effects of microgravity. Mechanical forces experienced by the organism can be transmitted to cells through molecules that allow cells to bind to the extracellular matrix and through other types of molecules which bind cells to each other. These molecules are coupled in large complexes of proteins to structural elements such as the actin cytoskeleton that give the cell the ability to sense, resist and respond to force. Application of small forces to tissue culture cells causes local elevation of intracellular calcium through stretch activated ion channels, increased tyrosine phosphorylation and a restructuring of the actin cytoskeleton. Using collagen coated iron oxide beads and strong magnets, we can apply different levels of force to cells in culture. We have found that force application causes the cells to polymerize actin at the site of mechanical deformation and unexpectedly, to depolymerize actin across the rest of the cell. Observations of GFP- actin expressing cells demonstrate that actin accumulates at the site of deformation within the first five minutes of force application and is maintained for many tens of minutes after force is removed. Consistent with the reinforcement of the cytoskeletal structures underlying the integrin-bead interaction, force also alters the motion of bound magnetic beads. This effect is seen following the removal of the magnetic field, and is only partially ablated by actin disruption with cytochalsin B. While actin is polymerizing locally at the site of force application, force also stimulates a global reduction in actin filament content within the cells. We have

Mechanisms of Dietary Response in Mice and Primates: A Role for EGR1 in Regulating the Reaction to Human-Specific Nutritional Content

PubMed Central

Weng, Kai; Hu, Haiyang; Xu, Augix Guohua; Khaitovich, Philipp; Somel, Mehmet

2012-01-01

Background Humans have a widely different diet from other primate species, and are dependent on its high nutritional content. The molecular mechanisms responsible for adaptation to the human diet are currently unknown. Here, we addressed this question by investigating whether the gene expression response observed in mice fed human and chimpanzee diets involves the same regulatory mechanisms as expression differences between humans and chimpanzees. Results Using mouse and primate transcriptomic data, we identified the transcription factor EGR1 (early growth response 1) as a putative regulator of diet-related differential gene expression between human and chimpanzee livers. Specifically, we predict that EGR1 regulates the response to the high caloric content of human diets. However, we also show that close to 90% of the dietary response to the primate diet found in mice, is not observed in primates. This might be explained by changes in tissue-specific gene expression between taxa. Conclusion Our results suggest that the gene expression response to the nutritionally rich human diet is partially mediated by the transcription factor EGR1. While this EGR1-driven response is conserved between mice and primates, the bulk of the mouse response to human and chimpanzee dietary differences is not observed in primates. This result highlights the rapid evolution of diet-related expression regulation and underscores potential limitations of mouse models in dietary studies. PMID:22937124

Early detection and rapid response

USGS Publications Warehouse

Westbrooks, Randy G.; Eplee, Robert E.; Simberloff, Daniel; Rejmánek, Marcel

2011-01-01

Prevention is the first line of defense against introduced invasive species - it is always preferable to prevent the introduction of new invaders into a region or country. However, it is not always possible to detect all alien hitchhikers imported in cargo, or to predict with any degree of certainty which introduced species will become invasive over time. Fortunately, the majority of introduced plants and animals don't become invasive. But, according to scientists at Cornell University, costs and losses due to species that do become invasive are now estimated to be over $137 billion/year in the United States. Early detection and rapid response (EDRR) is the second line of defense against introduced invasive species - EDRR is the preferred management strategy for preventing the establishment and spread of invasive species. Over the past 50 years, there has been a gradual shift away from large and medium scale federal/state single-agency-led weed eradication programs in the United States, to smaller interagency-led projects involving impacted and potential stakeholders. The importance of volunteer weed spotters in detecting and reporting suspected new invasive species has also been recognized in recent years.

Mechanisms of the placebo response in pain in osteoarthritis.

PubMed

Abhishek, A; Doherty, M

2013-09-01

Administration of a placebo associates with symptomatic improvement in many conditions--the so-called placebo response. In this review we explain the concept of placebo response, examine the data that supports existence in osteoarthritis (OA), and discuss its possible mechanisms and determinants. A Pubmed literature search was carried out. Key articles were identified, and their findings discussed in a narrative review. Pain, stiffness, self-reported function and physician-global assessment in OA clearly improve in response to placebo. However, more objective measures such as quadriceps strength and radiographic progression appear less responsive. Although not directly studied in OA, contextual effects, patient expectation and conditioning are believed to be the main mechanisms. Neurotransmitter changes that mediate placebo-induced analgesia include increased endogenous opioid levels, increased dopamine levels, and reduced levels of cholecystokinin. Almost all parts of the brain involved in pain processing are influenced during placebo-induced analgesia. Determinants of the magnitude of placebo response include the patient-practitioner interaction, treatment response expectancy, knowledge of being treated, patient personality traits and placebo specific factors such as the route and frequency of administration, branding, and treatment costs. Clearer understanding of the neurobiology of placebo response validates its existence as a real phenomenon. Although routine administration of placebo for symptomatic improvement is difficult to justify, contextual factors that enhance treatment response should be employed in the management of chronic painful conditions such as OA where available treatments have only modest efficacy. Copyright © 2013 Osteoarthritis Research Society International. Published by Elsevier Ltd. All rights reserved.

[Health threats and health system crises. An approach to early warning and response. 2008 SESPAS Report].

PubMed

Simón Soria, Fernando; Guillén Enríquez, Francisco Javier

2008-04-01

The world is changing more and faster than ever before. New diseases are coming to light each year, controlled diseases are reemerging as potential threats, and natural or man-made disasters are increasingly affecting human health. The "International Health Regulations (2005)" reflect the changes in the response of public health to this new situation. Surveillance of specific diseases and predefined control measures have been replaced by surveillance of public health events of international concern and control measures adapted to each situation. The public health events of international interest are characterized by their seriousness, predictability, the risk of international spread and potential for travel or trade restrictions. The development of the European Early Warning and Response System in 1998 and the creation of the European Center for Disease Prevention and Control in 2005 demonstrate political commitment in Europe, with early detection of and response to public health threats. However, timely risk evaluation and response at a national level requires improved data digitalization and accessibility, automatic notification processes, data analysis and dissemination of information, the combination of information from multiple sources and adaptation of public health services. The autonomous regions in Spain are initiating this adaptation process, but interoperability between systems and the development of guidelines for a coordinated response should be steered by the National Interregional Health Council and coordinated by the Ministry of Health. Efficient early warning systems of health threats that allow for a timely response and reduce uncertainty about information would help to minimize the risk of public health crises. The profile of public health threats is nonspecific. Early detection of threats requires access to information from multiple sources and efficient risk assessment. Key factors for improving the response to public health threats are the

Abnormal early brain responses during visual search are evident in schizophrenia but not bipolar affective disorder.

PubMed

VanMeerten, Nicolaas J; Dubke, Rachel E; Stanwyck, John J; Kang, Seung Suk; Sponheim, Scott R

2016-01-01

People with schizophrenia show deficits in processing visual stimuli but neural abnormalities underlying the deficits are unclear and it is unknown whether such functional brain abnormalities are present in other severe mental disorders or in individuals who carry genetic liability for schizophrenia. To better characterize brain responses underlying visual search deficits and test their specificity to schizophrenia we gathered behavioral and electrophysiological responses during visual search (i.e., Span of Apprehension [SOA] task) from 38 people with schizophrenia, 31 people with bipolar disorder, 58 biological relatives of people with schizophrenia, 37 biological relatives of people with bipolar disorder, and 65 non-psychiatric control participants. Through subtracting neural responses associated with purely sensory aspects of the stimuli we found that people with schizophrenia exhibited reduced early posterior task-related neural responses (i.e., Span Endogenous Negativity [SEN]) while other groups showed normative responses. People with schizophrenia exhibited longer reaction times than controls during visual search but nearly identical accuracy. Those individuals with schizophrenia who had larger SENs performed more efficiently (i.e., shorter reaction times) on the SOA task suggesting that modulation of early visual cortical responses facilitated their visual search. People with schizophrenia also exhibited a diminished P300 response compared to other groups. Unaffected first-degree relatives of people with bipolar disorder and schizophrenia showed an amplified N1 response over posterior brain regions in comparison to other groups. Diminished early posterior brain responses are associated with impaired visual search in schizophrenia and appear to be specifically associated with the neuropathology of schizophrenia. Published by Elsevier B.V.

Exposure to dim light at night during early development increases adult anxiety-like responses.

PubMed

Borniger, Jeremy C; McHenry, Zachary D; Abi Salloum, Bachir A; Nelson, Randy J

2014-06-22

Early experiences produce effects that may persist throughout life. Therefore, to understand adult phenotype, it is important to investigate the role of early environmental stimuli in adult behavior and health. Artificial light at night (LAN) is an increasingly common phenomenon throughout the world. However, animals, including humans, evolved under dark night conditions. Many studies have revealed affective, immune, and metabolic alterations provoked by aberrant light exposure and subsequent circadian disruption. Pups are receptive to entraining cues from the mother and then light early during development, raising the possibility that the early life light environment may influence subsequent behavior. Thus, to investigate potential influences of early life exposure to LAN on adult phenotype, we exposed mice to dim (~5 lux; full spectrum white light) or dark (~0 lux) nights pre- and/or postnatally. After weaning at 3 weeks of age, all mice were maintained in dark nights until adulthood (9 weeks of age) when behavior was assessed. Mice exposed to dim light in early life increased anxiety-like behavior and fearful responses on the elevated plus maze and passive avoidance tests. These mice also displayed reduced growth rates, which ultimately normalized during adolescence. mRNA expression of brain derived neurotrophic factor (BDNF), a neurotrophin previously linked to early life environment and adult phenotype, was not altered in the prefrontal cortex or hippocampus by early life LAN exposure. Serum corticosterone concentrations were similar between groups at weaning, suggesting that early life LAN does not elicit a long-term physiologic stress response. Dim light exposure did not influence behavior on the open field, novel object, sucrose anhedonia, or forced swim tests. Our data highlight the potential deleterious consequences of low levels of light during early life to development and subsequent behavior. Whether these changes are due to altered maternal behavior

Response mechanism of post-earthquake slopes under heavy rainfall

NASA Astrophysics Data System (ADS)

Qiu, Hong-zhi; Kong, Ji-ming; Wang, Ren-chao; Cui, Yun; Huang, Sen-wang

2017-07-01

This paper uses the catastrophic landslide that occurred in Zhongxing Town, Dujiangyan City, as an example to study the formation mechanism of landslides induced by heavy rainfall in the post-Wenchuan earthquake area. The deformation characteristics of a slope under seismic loading were investigated via a shaking table test. The results show that a large number of cracks formed in the slope due to the tensile and shear forces of the vibrations, and most of the cracks had angles of approximately 45° with respect to the horizontal. A series of flume tests were performed to show how the duration and intensity of rainfall influence the responses of the shaken and non-shaken slopes. Wetting fronts were recorded under different rainfall intensities, and the depth of rainfall infiltration was greater in the shaken slope than in the non-shaken slope because the former experienced a greater extreme rainfall intensity under the same early rainfall and rainfall duration conditions. At the beginning of the rainfall infiltration experiment, the pore water pressure in the slope was negative, and settling occurred at the top of the slope. With increasing rainfall, the pore water pressure changed from negative to positive, and cracks were observed on the back surface of the slope and the shear outlet of the landslide on the front of the slope. The shaken slope was more susceptible to crack formation than the non-shaken slope under the same rainfall conditions. A comparison of the responses of the shaken and non-shaken slopes under heavy rainfall revealed that cracks formed by earthquakes provided channels for infiltration. Soil particles in the cracks of slopes were washed away, and the pore water pressure increased rapidly, especially the transient pore water pressure in the slope caused by short-term concentrated rainfall which decreased rock strength and slope stability.

Evaluating cardiac risk: exposure response analysis in early clinical drug development.

PubMed

Grenier, Julie; Paglialunga, Sabina; Morimoto, Bruce H; Lester, Robert M

2018-01-01

The assessment of a drug's cardiac liability has undergone considerable metamorphosis by regulators since International Council for Harmonization of Technical Requirement for Pharmaceuticals for Human Use E14 guideline was introduced in 2005. Drug developers now have a choice in how proarrhythmia risk can be evaluated; the options include a dedicated thorough QT (TQT) study or exposure response (ER) modeling of intensive electrocardiogram (ECG) captured in early clinical development. The alternative approach of ER modeling was incorporated into a guidance document in 2015 as a primary analysis tool which could be utilized in early phase dose escalation studies as an option to perform a dedicated TQT trial. This review will describe the current state of ER modeling of intensive ECG data collected during early clinical drug development; the requirements with regard to the use of a positive control; and address the challenges and opportunities of this alternative approach to assessing QT liability.

Micelle Morphology and Mechanical Response of Triblock Gels

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

Seitz, Michelle E.; Burghardt, Wesley R.; Shull, Kenneth R.

2010-01-12

The effect of polymer concentration on mechanical response and micelle morphology of ABA and AB copolymers in B-selective solvents has been systematically studied. Micelle morphology was determined using a combination of small-angle X-ray scattering, shear, and birefringence while mechanical response at low and high strains was determined using indentation techniques. Self-consistent field theory calculations were used to determine micelle volume fraction profiles and to construct an equilibrium phase map. The transition from spherical to cylindrical micelles increases the triblock gel modulus and energy dissipation. Combining knowledge of gel relaxation time, which determines the rate at which the gel can equilibratemore » its micelle structure, with the equilibrium phase map allows estimation of the experimental temperatures and time scales over which kinetic trapping will arrest micelle structure evolution. Kinetic trapping enables cylindrical morphologies to be obtained at significantly lower polymer fractions than is possible in equilibrated systems.« less

Forensic Study of Early Failures with Unbonded Concrete Overlays

DOT National Transportation Integrated Search

2017-11-01

A forensic investigation was conducted to identify failure mechanisms responsible for early failures of unbonded concrete overlays on selected projects in Ohio, including I-70 in Madison County, I-77 in Washington and Noble Counties, and I-90 in Lake...

A biphasic endothelial stress-survival mechanism regulates the cellular response to vascular endothelial growth factor A

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

Latham, Antony M.; Odell, Adam F.; Mughal, Nadeem A.

2012-11-01

Vascular endothelial growth factor A (VEGF-A) is an essential cytokine that regulates endothelial function and angiogenesis. VEGF-A binding to endothelial receptor tyrosine kinases such as VEGFR1 and VEGFR2 triggers cellular responses including survival, proliferation and new blood vessel sprouting. Increased levels of a soluble VEGFR1 splice variant (sFlt-1) correlate with endothelial dysfunction in pathologies such as pre-eclampsia; however the cellular mechanism(s) underlying the regulation and function of sFlt-1 are unclear. Here, we demonstrate the existence of a biphasic stress response in endothelial cells, using serum deprivation as a model of endothelial dysfunction. The early phase is characterized by a highmore » VEGFR2:sFlt-1 ratio, which is reversed in the late phase. A functional consequence is a short-term increase in VEGF-A-stimulated intracellular signaling. In the late phase, sFlt-1 is secreted and deposited at the extracellular matrix. We hypothesized that under stress, increased endothelial sFlt-1 levels reduce VEGF-A bioavailability: VEGF-A treatment induces sFlt-1 expression at the cell surface and VEGF-A silencing inhibits sFlt-1 anchorage to the extracellular matrix. Treatment with recombinant sFlt-1 inhibits VEGF-A-stimulated in vitro angiogenesis and sFlt-1 silencing enhances this process. In this response, increased VEGFR2 levels are regulated by the phosphatidylinositol-3-kinase and PKB/Akt signaling pathways and increased sFlt-1 levels by the ERK1/2 signaling pathway. We conclude that during serum withdrawal, cellular sensing of environmental stress modulates sFlt-1 and VEGFR2 levels, regulating VEGF-A bioavailability and ensuring cell survival takes precedence over cell proliferation and migration. These findings may underpin an important mechanism contributing to endothelial dysfunction in pathological states. -- Highlights: Black-Right-Pointing-Pointer Endothelial cells mount a stress response under conditions of low serum. Black

Exposure to Violence Predicting Cortisol Response During Adolescence and Early Adulthood: Understanding Moderating Factors

PubMed Central

Heinze, Justin E.; Miller, Alison L.; Stoddard, Sarah A.; Zimmerman, Marc A.

2014-01-01

Previous research on the association between violence and biological stress regulation has been largely cross-sectional, and has also focused on childhood. Using longitudinal data from a low-income, high-risk, predominantly African-American sample (n = 266; 57 % female), we tested hypotheses about the influence of cumulative exposure to violence during adolescence and early adulthood on cortisol responses in early adulthood. We found that cumulative exposure to violence predicted an attenuated cortisol response. Further, we tested whether sex, mothers’ support, or fathers’ support moderated the effect of exposure to violence on cortisol responses. We found that the effect of cumulative exposure to violence on cortisol was modified by sex; specifically, males exposed to violence exhibited a more attenuated response pattern. In addition, the effect of cumulative exposure to violence on cortisol was moderated by the presence of fathers’ support during adolescence. The findings contribute to a better understanding of how cumulative exposure to violence influences biological outcomes, emphasizing the need to understand sex and parental support as moderators of risk. PMID:24458765

On the nature and consequences of early loss.

PubMed

Hofer, M A

1996-01-01

To describe how an animal model system can be used to explore basic questions about the nature of loss and the effects of early loss on later vulnerability to disease. The physiological and behavioral responses of infant rats to separation from their mothers are first described and then analyzed experimentally into component mechanisms. These studies have revealed an extensive layer of processes underlying the psychological constructs generally used to understand the response to loss. Hidden within the observable interactions of parent and offspring, we found a number of discrete sensorimotor, thermal, and nutrient-based events that have unexpected long-term regulatory effects on specific components of infant physiology and behavior. Release from all of these inhibitory and excitatory regulators together during maternal separation constitutes a novel mechanism by which the experience of loss can be translated into a complex patterned response. Evidence for early regulatory processes has also been found in monkey and human mother-infant interactions. Here they may well constitute the building blocks from which attachment and object representations develop. We and others have found long-term effects of loss, and of selective replacement of regulators, on behavioral development and on later vulnerability to disease. The results give us a new understanding of early attachment as a developmental force and of human grief as a risk to health.

The microtubule associated protein END BINDING 1 represses root responses to mechanical cues.

PubMed

Gleeson, Laura; Squires, Shannon; Bisgrove, Sherryl R

2012-05-01

The ability of roots to navigate around rocks and other debris as they grow through the soil requires a mechanism for detecting and responding to input from both touch and gravity sensing systems. The microtubule associated protein END BINDING 1b (EB1b) is involved in this process as mutants have defects responding to combinations of touch and gravity cues. This study investigates the role of EB1b in root responses to mechanical cues. We find that eb1b-1 mutant roots exhibit an increase over wild type in their response to touch and that the expression of EB1b genes in transgenic mutants restores the response to wild type levels, indicating that EB1b is an inhibitor of the response. Mutant roots are also hypersensitive to increased levels of mechanical stimulation, revealing the presence of another process that activates the response. These findings are supported by analyses of double mutants between eb1b-1 and seedlings carrying mutations in PHOSPHOGLUCOMUTASE (PGM), ALTERED RESPONSE TO GRAVITY1 (ARG1), or TOUCH3 (TCH3), genes that encode proteins involved in gravity sensing, signaling, or touch responses, respectively. A model is proposed in which root responses to mechanical cues are modulated by at least two competing regulatory processes, one that promotes touch-mediated growth and another, regulated by EB1b, which dampens root responses to touch and enhances gravitropism. © 2012. Published by Elsevier Ireland Ltd. All rights reserved.

Mechanical origins of rightward torsion in early chick brain development

NASA Astrophysics Data System (ADS)

Chen, Zi; Guo, Qiaohang; Dai, Eric; Taber, Larry

2015-03-01

During early development, the neural tube of the chick embryo undergoes a combination of progressive ventral bending and rightward torsion. This torsional deformation is one of the major organ-level left-right asymmetry events in development. Previous studies suggested that bending is mainly due to differential growth, however, the mechanism for torsion remains poorly understood. Since the heart almost always loops rightwards that the brain twists, researchers have speculated that heart looping affects the direction of brain torsion. However, direct evidence is lacking, nor is the mechanical origin of such torsion understood. In our study, experimental perturbations show that the bending and torsional deformations in the brain are coupled and that the vitelline membrane applies an external load necessary for torsion to occur. Moreover, the asymmetry of the looping heart gives rise to the chirality of the twisted brain. A computational model and a 3D printed physical model are employed to help interpret these findings. Our work clarifies the mechanical origins of brain torsion and the associated left-right asymmetry, and further reveals that the asymmetric development in one organ can induce the asymmetry of another developing organ through mechanics, reminiscent of D'Arcy Thompson's view of biological form as ``diagram of forces''. Z.C. is supported by the Society in Science - Branco Weiss fellowship, administered by ETH Zurich. L.A.T acknowledges the support from NIH Grants R01 GM075200 and R01 NS070918.

Early vs. asymptotic growth responses of herbaceous plants to elevated CO[sub 2

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

Thomas, S.C.; Jasienski, M.; Bazzaz, F.A.

1999-07-01

Although many studies have examined the effects of elevated carbon dioxide on plant growth,'' the dynamics of growth involve at least two parameters, namely, an early rate of exponential size increase and an asymptotic size reached late in plant ontogeny. The common practice of quantifying CO[sub 2] responses as a single response ratio thus obscures two qualitatively distinct kinds of effects. The present experiment examines effects of elevated CO[sub 2] on both early and asymptotic growth parameters in eight C[sub 3] herbaceous plant species (Abutilon theophrasti, Cassia obtusifolia, Plantago major, Rumex crispus, Taraxacum officinale, Dactylis glomerata, Lolium multiflorum, and Panicummore » dichotomoflorum). Plants were grown for 118--172 d in a factorial design of CO[sub 2] (350 and 700 [micro]L/L) and plant density (individually grown vs. high-density monocultures) under edaphic conditions approximating those of coastal areas in Massachusetts. For Abutilon theophrasti, intraspecific patterns of plant response were also assessed using eight genotypes randomly sampled from a natural population and propagated as inbred lines.« less

Exercise Improves Host Response to Influenza Viral Infection in Obese and Non-Obese Mice through Different Mechanisms

PubMed Central

Warren, Kristi J.; Olson, Molly M.; Thompson, Nicholas J.; Cahill, Mackenzie L.; Wyatt, Todd A.; Yoon, Kyoungjin J.; Loiacono, Christina M.; Kohut, Marian L.

2015-01-01

Obesity has been associated with greater severity of influenza virus infection and impaired host defense. Exercise may confer health benefits even when weight loss is not achieved, but it has not been determined if regular exercise improves immune defense against influenza A virus (IAV) in the obese condition. In this study, diet-induced obese mice and lean control mice exercised for eight weeks followed by influenza viral infection. Exercise reduced disease severity in both obese and non-obese mice, but the mechanisms differed. Exercise reversed the obesity-associated delay in bronchoalveolar-lavage (BAL) cell infiltration, restored BAL cytokine and chemokine production, and increased ciliary beat frequency and IFNα-related gene expression. In non-obese mice, exercise treatment reduced lung viral load, increased Type-I-IFN-related gene expression early during infection, but reduced BAL inflammatory cytokines and chemokines. In both obese and non-obese mice, exercise increased serum anti-influenza virus specific IgG2c antibody, increased CD8+ T cell percentage in BAL, and reduced TNFα by influenza viral NP-peptide-responding CD8+ T cells. Overall, the results suggest that exercise “restores” the immune response of obese mice to a phenotype similar to non-obese mice by improving the delay in immune activation. In contrast, in non-obese mice exercise treatment results in an early reduction in lung viral load and limited inflammatory response. PMID:26110868

Practice patterns and outcomes associated with early sedation depth in mechanically ventilated patients: a systematic review protocol.

PubMed

Stephens, Robert J; Dettmer, Matthew R; Roberts, Brian W; Fowler, Susan A; Fuller, Brian M

2017-06-09

Mechanical ventilation is a commonly performed intervention in critically ill patients. Frequently, these patients experience deep sedation early in their clinical course. Emerging data suggest that the practice of early deep sedation may negatively impact patient outcomes. The purpose of this review is to assess the world's literature to describe and determine the impact of early deep sedation on the outcomes of mechanically ventilated patients. Randomised controlled trials and non-randomised studies will be eligible for inclusion in this systematic review. With the assistance of a medical librarian, we will comprehensively search MEDLINE, Embase, Scopus, Cochrane Central Register of Controlled Trials, Database of Abstracts of Reviews and Effects, and Cochrane Database of Systematic Reviews for peer-reviewed literature. Grey literature from appropriate professional society conferences, held from 2010 to 2017, will be reviewed manually. Two authors will independently review all search results, and disagreements will be resolved through arbitration by a third author. If appropriate, meta-analysis will be used for quantitative analysis of the data. Heterogeneity between studies will be assessed using the I 2 statistic. The proposed systematic review will not collect data that are associated with individual patients and does not require ethical approval. Results of this study will contribute to the understanding of early sedation, identify future research targets and guide early care in mechanically ventilated patients. This systematic review has been registered in the international prospective register of systematic reviews (PROSPERO #CRD42017057264). © Article author(s) (or their employer(s) unless otherwise stated in the text of the article) 2017. All rights reserved. No commercial use is permitted unless otherwise expressly granted.

The Early Development of Human Mirror Mechanisms: Evidence from Electromyographic Recordings at 3 and 6 Months

ERIC Educational Resources Information Center

Turati, Chiara; Natale, Elena; Bolognini, Nadia; Senna, Irene; Picozzi, Marta; Longhi, Elena; Cassia, Viola Macchi

2013-01-01

In primates and adult humans direct understanding of others' action is provided by mirror mechanisms matching action observation and action execution (e.g. Casile, Caggiano & Ferrari, 2011). Despite the growing body of evidence detailing the existence of these mechanisms in the adult human brain, their origins and early development are…

Early-Life Stress: From Neuroendocrine Mechanisms to Stress-Related Disorders.

PubMed

Pervanidou, Panagiota; Chrousos, George P

2018-06-08

Stress exposure is highly prevalent in the general population; however, the experience of stress during vulnerable periods of development has substantial and permanent effects on brain structure and function and physical health in adulthood. Stress, the state of threatened homeostasis, is generally associated with a time-limited activation of the stress system, i.e., the hypothalamic-pituitary-adrenal axis and the arousal/sympathetic nervous system, tailored to the stressful stimulus also known as the stressor. On the other hand, chronic stress may be associated with lingering hyper- or hyposecretion of mediators of the stress system. This chronic condition is called dyshomeostasis, allostasis, or cacostasis and is associated with increased mental and physical morbidity in the long term. Stressful or traumatic experiences during fetal life, early childhood, and adolescence have been related to persistent neuroendocrine and epigenetic changes. Further, brain structures involved in the stress response, such as those of the stress system, the hippocampus, and the amygdala, may be programmed early on for a life of adversity. © 2018 S. Karger AG, Basel.

Mechanics regulates ATP-stimulated collective calcium response in fibroblast cells

PubMed Central

Lembong, Josephine; Sabass, Benedikt; Sun, Bo; Rogers, Matthew E.; Stone, Howard A.

2015-01-01

Cells constantly sense their chemical and mechanical environments. We study the effect of mechanics on the ATP-induced collective calcium response of fibroblast cells in experiments that mimic various tissue environments. We find that closely packed two-dimensional cell cultures on a soft polyacrylamide gel (Young's modulus E = 690 Pa) contain more cells exhibiting calcium oscillations than cultures on a rigid substrate (E = 36 000 Pa). Calcium responses of cells on soft substrates show a slower decay of calcium level relative to those on rigid substrates. Actin enhancement and disruption experiments for the cell cultures allow us to conclude that actin filaments determine the collective Ca2+ oscillatory behaviour in the culture. Inhibition of gap junctions results in a decrease of the oscillation period and reduced correlation of calcium responses, which suggests additional complexity of signalling upon cell–cell contact. Moreover, the frequency of calcium oscillations is independent of the rigidity of the substrate but depends on ATP concentration. We compare our results with those from similar experiments on individual cells. Overall, our observations show that collective chemical signalling in cell cultures via calcium depends critically on the mechanical environment. PMID:26063818

Evidence that the human cutaneous venoarteriolar response is not mediated by adrenergic mechanisms

NASA Technical Reports Server (NTRS)

Crandall, C. G.; Shibasaki, M.; Yen, T. C.

2002-01-01

The venoarteriolar response causes vasoconstriction to skin and muscle via local mechanisms secondary to venous congestion. The purpose of this project was to investigate whether this response occurs through alpha-adrenergic mechanisms. In supine individuals, forearm skin blood flow was monitored via laser-Doppler flowmetry over sites following local administration of terazosin (alpha(1)-antagonist), yohimbine (alpha(2)-antagonist), phentolamine (non-selective alpha-antagonist) and bretylium tosylate (inhibits neurotransmission of adrenergic nerves) via intradermal microdialysis or intradermal injection. In addition, skin blood flow was monitored over an area of forearm skin that was locally anaesthetized via application of EMLA (2.5 % lidocaine (lignocaine) and 2.5 % prilocaine) cream. Skin blood flow was also monitored over adjacent sites that received the vehicle for the specified drug. Each trial was performed on a minimum of seven subjects and on separate days. The venoarteriolar response was engaged by lowering the subject's arm from heart level such that the sites of skin blood flow measurement were 34 +/- 1 cm below the heart. The arm remained in this position for 2 min. Selective and non-selective alpha-adrenoceptor antagonism and presynaptic inhibition of adrenergic neurotransmission did not abolish the venoarteriolar response. However, local anaesthesia blocked the venoarteriolar response without altering alpha-adrenergic mediated vasoconstriction. These data suggest that the venoarteriolar response does not occur through adrenergic mechanisms as previously reported. Rather, the venoarteriolar response may due to myogenic mechanisms associated with changes in vascular pressure or is mediated by a non-adrenergic, but neurally mediated, local mechanism.

Ethanol, saccharin, and quinine: early ontogeny of taste responsiveness and intake.

PubMed

Kozlov, Andrey P; Varlinskaya, Elena I; Spear, Norman E

2008-02-01

Rat pups demonstrate high levels of immediate acceptance of ethanol during the first 2 weeks of postnatal life. Given that the taste of ethanol is most likely perceived by infant rats as a combination of sweet and bitter, high intake of ethanol early in ontogeny may be associated with age-related enhanced responsiveness to the sweet component of ethanol taste, as well as with ontogenetic decreases in sensitivity to its bitter component. Therefore, the present study compared responsiveness to ethanol and solutions with bitter (quinine) and sweet (saccharin) taste in terms of intake and palatability across the first 2 weeks of postnatal life. Characteristic patterns of responsiveness to 10% (v/v) ethanol, 0.1% saccharin, 0.2% quinine, and water in terms of taste reactivity and fluid intake were assessed in rat pups tested on postnatal day (P) 4, 9, or 12 using a new technique of on-line monitoring of fluid flow through a two-channel intraoral cannula. Taste reactivity included analysis of ingestive and aversive responses following six intraoral infusions of the test fluids. This taste reactivity probe was followed by the intake test, in which animals were allowed to voluntarily ingest fluids from an intraoral cannula. Pups of all ages showed more appetitive responses to saccharin and ethanol than to water or quinine. No age-related differences were apparent in taste responsiveness to saccharin and ethanol. However, the age-related pattern of ethanol intake drastically differed from that of saccharin. Intake of saccharin increased from P4 to P9 and decreased substantially by P12, whereas intake of ethanol gradually increased from P4 to P12. Intake of ethanol was significantly lower than intake of saccharin on P9, whereas P12 pups took in more ethanol than saccharin. The findings of the present study indicate ontogenetic dissociations between taste reactivity to ethanol and saccharin and intake of these solutions, and suggest that high acceptance of ethanol early in

Early improvement and response to antidepressant medications in adults with major depressive disorder. Meta-analysis and study of a sample with treatment-resistant depression.

PubMed

Olgiati, Paolo; Serretti, Alessandro; Souery, Daniel; Dold, Markus; Kasper, Siegfried; Montgomery, Stuart; Zohar, Joseph; Mendlewicz, Julien

2018-02-01

Initial improvement in the first weeks of antidepressant (AD) treatment is a useful early predictor of complete AD response. We performed a meta-analysis of AD studies to investigate whether a partial decrease in depressive symptoms by week 4 was associated with response and remission by weeks 6-14 in major depressive disorder (MDD). Finally, we focused on treatment-resistant depression (TRD: lack of response to prior AD) to test the impact of early improvement on a second AD treatment outcome and to compare different switching strategies. Meta-analysis was conducted on AD naturalistic studies published between 01.01.2000 and 06.30.2017. TRD was an exclusion criterion. TRD was analyzed in 407 MDD patients treated with venlafaxine for 6 weeks. The MADRS was used to define very early improvement (VEI: > 20% decrease at week 2), early improvement (EI: > 30% decrease at week 4) and remission (week 6 MADRS < 10). A theoretical model was used to simulate AD switch in TRD patients who failed to achieve remission (Algorithm A), VEI (Algorithm B) or EI (Algorithm C). Our meta-analysis (9 studies; N = 6185) showed significant associations between early improvement, response (OR: 3.28 95% C.I: 2.06-5.20) and remission (OR: 2.10 95% C.I: 1.53-2.87). 24.6% of TRD sample remitted. VEI was a poor outcome predictor: sensitivity = 0.52 (0.40-0.63); specificity = 0.82 (0.76-0.86); AUC = 0.67 (0.62-0.71). EI had a moderate predictive power: sensitivity = 0.87 (0.77-0.93); specificity = 0.71 (0.66-0.77); AUC = 0.76 (0.71-0.80). The best treatment scenario was Algorithm C (switch after 4 weeks) in which remission rate was marginally increased (35.1% vs 33.7% of Algorithm A). Algorithm B (switch after 2 weeks) led to a 4.3% decrease in remission compared to Algorithm A. Inclusion of a naturalistic sample without a control arm; simulation of treatments. Although literature data suggest a correlation between an initial improvement of depressive symptoms and later response and remission

A Mechanism for Error Detection in Speeded Response Time Tasks

ERIC Educational Resources Information Center

Holroyd, Clay B.; Yeung, Nick; Coles, Michael G. H.; Cohen, Jonathan D.

2005-01-01

The concept of error detection plays a central role in theories of executive control. In this article, the authors present a mechanism that can rapidly detect errors in speeded response time tasks. This error monitor assigns values to the output of cognitive processes involved in stimulus categorization and response generation and detects errors…

Mechanics of responsive polymers via conformationally switchable molecules

NASA Astrophysics Data System (ADS)

Brighenti, Roberto; Artoni, Federico; Vernerey, Franck; Torelli, Martina; Pedrini, Alessandro; Domenichelli, Ilaria; Dalcanale, Enrico

2018-04-01

Active materials are those capable of giving some physical reaction under external stimuli coming from the environment such as temperature, pH, light, mechanical stress, etc. Reactive polymeric materials can be obtained through the introduction of switchable molecules in their network, i.e. molecules having two distinct stable conformations: if properly linked to the hosting polymer chains, the switching from one state to the other can promote a mechanical reaction of the material, detectable at the macroscale, and thus enables us to tune the response according to a desired functionality. In the present paper, the main aspects of the mechanical behavior of polymeric materials with embedded switchable molecules-properly linked to the polymer's chains-are presented and discussed. Starting from the micro mechanisms occurring in such active material, a continuum model is developed, providing a straightforward implementation in computational approaches. Finally, some experimental outcomes related to a switchable molecules (known as quinoxaline cavitands) added to an elastomeric PDMS under chemical stimuli, are presented and quantitatively discussed through the use of the developed mechanical framework.

Modeling and parameter identification of impulse response matrix of mechanical systems

NASA Astrophysics Data System (ADS)

Bordatchev, Evgueni V.

1998-12-01

A method for studying the problem of modeling, identification and analysis of mechanical system dynamic characteristic in view of the impulse response matrix for the purpose of adaptive control is developed here. Two types of the impulse response matrices are considered: (i) on displacement, which describes the space-coupled relationship between vectors of the force and simulated displacement, which describes the space-coupled relationship between vectors of the force and simulated displacement and (ii) on acceleration, which also describes the space-coupled relationship between the vectors of the force and measured acceleration. The idea of identification consists of: (a) the practical obtaining of the impulse response matrix on acceleration by 'impact-response' technique; (b) the modeling and parameter estimation of the each impulse response function on acceleration through the fundamental representation of the impulse response function on displacement as a sum of the damped sine curves applying linear and non-linear least square methods; (c) simulating the impulse provides the additional possibility to calculate masses, damper and spring constants. The damped natural frequencies are used as a priori information and are found through the standard FFT analysis. The problem of double numerical integration is avoided by taking two derivations of the fundamental dynamic model of a mechanical system as linear combination of the mass-damper-spring subsystems. The identified impulse response matrix on displacement represents the dynamic properties of the mechanical system. From the engineering point of view, this matrix can be also understood as a 'dynamic passport' of the mechanical system and can be used for dynamic certification and analysis of the dynamic quality. In addition, the suggested approach mathematically reproduces amplitude-frequency response matrix in a low-frequency band and on zero frequency. This allows the possibility of determining the matrix of the

Designing a Measurement Framework for Response to Intervention in Early Childhood Programs

ERIC Educational Resources Information Center

McConnell, Scott R.; Wackerle-Hollman, Alisha K.; Roloff, Tracy A.; Rodriguez, Michael

2014-01-01

The overall architecture and major components of a measurement system designed and evaluated to support Response to Intervention (RTI) in the areas of language and literacy in early childhood programs are described. Efficient and reliable measurement is essential for implementing any viable RTI system, and implementing such a system in early…

PKM2 released by neutrophils at wound site facilitates early wound healing by promoting angiogenesis.

PubMed

Zhang, Yinwei; Li, Liangwei; Liu, Yuan; Liu, Zhi-Ren

2016-03-01

Neutrophils infiltration/activation following wound induction marks the early inflammatory response in wound repair. However, the role of the infiltrated/activated neutrophils in tissue regeneration/proliferation during wound repair is not well understood. Here, we report that infiltrated/activated neutrophils at wound site release pyruvate kinase M2 (PKM2) by its secretive mechanisms during early stages of wound repair. The released extracellular PKM2 facilitates early wound healing by promoting angiogenesis at wound site. Our studies reveal a new and important molecular linker between the early inflammatory response and proliferation phase in tissue repair process. © 2016 by the Wound Healing Society.

Mechanisms Regulating the Cardiac Output Response to Cyanide Infusion, a Model of Hypoxia

PubMed Central

Liang, Chang-seng; Huckabee, William E.

1973-01-01

When tissue metabolic changes like those of hypoxia were induced by intra-aortic infusion of cyanide in dogs, cardiac output began to increase after 3 to 5 min, reached a peak (220% of the control value) at 15 min, and returned to control in 40 min. This pattern of cardiac output rise was not altered by vagotomy with or without atropine pretreatment. However, this cardiac output response could be differentiated into three phases by pretreating the animals with agents that block specific activities of the sympatho-adrenal system. First, ganglionic blockade produced by mecamylamine or sympathetic nerve blockade by bretylium abolished the middle phase of the cardiac output seen in the untreated animal, but early and late phases still could be discerned. Second, beta-adrenergic receptor blockade produced by propranolol shortened the total duration of the cardiac output rise by abolishing the late phase. Third, when given together, propranolol and mecamylamine (or bretylium) prevented most of the cardiac output rise that follows the early phase. When cyanide was given to splenectomized dogs, the duration of the cardiac output response was not shortened, but the response became biphasic, resembling that seen after chemical sympathectomy. A similar biphasic response of the cardiac output also resulted from splenic denervation; sham operation or nephrectomy had no effect on the monophasic pattern of the normal response. Splenic venous blood obtained from cyanide-treated dogs, when infused intraportally, caused an increase in cardiac output in recipient dogs; similar infusion of arterial blood had no effects. These results suggest that the cardiac output response to cyanide infusion consists of three components: an early phase, related neither to the autonomic nervous system nor to circulating catecholamines; a middle phase, caused by a nonadrenergic humoral substance released from the spleen by sympathetic stimulation; and a late phase, dependent upon adrenergic receptors

Rapid and early α-fetoprotein and des-γ-carboxy prothrombin responses to initial arterial infusion chemotherapy predict treatment outcomes of advanced hepatocellular carcinoma

PubMed Central

OYAMA, KENJI; KODA, MASAHIKO; SUGIHARA, TAKAAKI; KISHINA, MANABU; MIYOSHI, KENICHI; OKAMOTO, TOSHIAKI; HODOTSUKA, MASANORI; FUJISE, YUKI; MATONO, TOMOMITSU; TOKUNAGA, SHIHO; OKAMOTO, KINYA; HOSHO, KEIKO; OKANO, JUNICHI; MURAWAKI, YOSHIKAZU

2015-01-01

The aim of the present study was to predict the effects of transarterial infusion (TAI) chemotherapy based on early changes in α-fetoprotein (AFP) and des-γ-carboxy prothrombin (DCP) in patients with advanced hepatocellular carcinoma (HCC). Seventy-four patients who underwent TAI with cisplatin, 5-fluorouracil, mitomycin C and epirubicin for advanced HCC were enrolled. Antitumor responses were evaluated 6 months after TAI. Rapid and early responses were defined as the ratio of AFP or DCP after 1 week and 1 month compared to baseline. A total of 5, 10, 17 and 42 patients had complete response (CR), partial response (PR), stable disease (SD) or progressive disease (PD), respectively. Early AFP response was significantly lower in the CR+PR compared to the SD+PD groups (P<0.01). The early DCP response was significantly lower in the CR+PR compared to the SD+PD. The sensitivity and specificity of rapid and early AFP responses in the CR+PR were 0.78 and 0.72, and 0.80 and 0.73, respectively, and those of rapid and early DCP responses were 0.67 and 0.65, and 0.77 and 0.71, respectively. The combination of AFP and DCP responses had higher specificity compared to AFP or DCP alone responses. Patients were divided into responder and non-responder groups to evaluate the prediction of survival outcome. Early responders of AFP, DCP and AFP+DCP, who were divided based on the cut-off values of CR+PR survived significantly longer than the non-responders (P<0.05). In conclusion, rapid or early responses of AFP and/or DCP levels 1 and 4 weeks after TAI chemotherapy helped to predict the treatment effects. PMID:26137283

[Early responses of soil fauna in three typical forests of south subtropical China to simulated N deposition addition].

PubMed

Xu, Guolian; Mo, Jiangming; Zhou, Guoyi

2005-07-01

In this paper, simulated N deposition addition (0, 50, 100 and 150 kg x hm(-2) x yr(-1)) by spreading water or NH4NO3 was conducted to study the early responses of soil fauna in three typical native forests (monsoon evergreen broadleaf forest, pine forest, and broadleaf-pine mixed forest) of subtropical China. The results showed that in monsoon evergreen broadleaf forest, N deposition addition had an obviously negative effect on the three indexes for soil fauna, but in pine forest, the positive effect was significant (P < 0. 05), and the soil fauna community could reach the level in mixed forest, even that in monsoon evergreen broadleaf forest at sometime. The responses in mixed forest were not obvious. In monsoon evergreen broadleaf forest, the negative effects were significant (P < 0.05) under medium N deposition, but not under low N deposition. In pine forest, the positive effect was significant (P < 0.05) under high N deposition, especially for the number of soil fauna groups. The results obtained might imply the N saturation-response mechanisms of forest ecosystems in subtropical China, and the conclusions from this study were also consisted with some related researches.

Girls' challenging social experiences in early adolescence predict neural response to rewards and depressive symptoms.

PubMed

Casement, Melynda D; Guyer, Amanda E; Hipwell, Alison E; McAloon, Rose L; Hoffmann, Amy M; Keenan, Kathryn E; Forbes, Erika E

2014-04-01

Developmental models of psychopathology posit that exposure to social stressors may confer risk for depression in adolescent girls by disrupting neural reward circuitry. The current study tested this hypothesis by examining the relationship between early adolescent social stressors and later neural reward processing and depressive symptoms. Participants were 120 girls from an ongoing longitudinal study of precursors to depression across adolescent development. Low parental warmth, peer victimization, and depressive symptoms were assessed when the girls were 11 and 12 years old, and participants completed a monetary reward guessing fMRI task and assessment of depressive symptoms at age 16. Results indicate that low parental warmth was associated with increased response to potential rewards in the medial prefrontal cortex (mPFC), striatum, and amygdala, whereas peer victimization was associated with decreased response to potential rewards in the mPFC. Furthermore, concurrent depressive symptoms were associated with increased reward anticipation response in mPFC and striatal regions that were also associated with early adolescent psychosocial stressors, with mPFC and striatal response mediating the association between social stressors and depressive symptoms. These findings are consistent with developmental models that emphasize the adverse impact of early psychosocial stressors on neural reward processing and risk for depression in adolescence. Copyright © 2013 The Authors. Published by Elsevier Ltd.. All rights reserved.

Development of visible-light responsive and mechanically enhanced "smart" UCST interpenetrating network hydrogels.

PubMed

Xu, Yifei; Ghag, Onkar; Reimann, Morgan; Sitterle, Philip; Chatterjee, Prithwish; Nofen, Elizabeth; Yu, Hongyu; Jiang, Hanqing; Dai, Lenore L

2017-12-20

An interpenetrating polymer network (IPN), chlorophyllin-incorporated environmentally responsive hydrogel was synthesized and exhibited the following features: enhanced mechanical properties, upper critical solution temperature (UCST) swelling behavior, and promising visible-light responsiveness. Poor mechanical properties are known challenges for hydrogel-based materials. By forming an interpenetrating network between polyacrylamide (PAAm) and poly(acrylic acid) (PAAc) polymer networks, the mechanical properties of the synthesized IPN hydrogels were significantly improved compared to hydrogels made of a single network of each polymer. The formation of the interpenetrating network was confirmed by Fourier Transform Infrared Spectroscopy (FTIR), the analysis of glass transition temperature, and a unique UCST responsive swelling behavior, which is in contrast to the more prevalent lower critical solution temperature (LCST) behaviour of environmentally responsive hydrogels. The visible-light responsiveness of the synthesized hydrogel also demonstrated a positive swelling behavior, and the effect of incorporating chlorophyllin as the chromophore unit was observed to reduce the average pore size and further enhance the mechanical properties of the hydrogel. This interpenetrating network system shows potential to serve as a new route in developing "smart" hydrogels using visible-light as a simple, inexpensive, and remotely controllable stimulus.

Chromatic Mechanical Response in 2-D Layered Transition Metal Dichalcogenide (TMDs) based Nanocomposites

PubMed Central

Rahneshin, Vahid; Khosravi, Farhad; Ziolkowska, Dominika A.; Jasinski, Jacek B.; Panchapakesan, Balaji

2016-01-01

The ability to convert photons of different wavelengths directly into mechanical motion is of significant interest in many energy conversion and reconfigurable technologies. Here, using few layer 2H-MoS2 nanosheets, layer by layer process of nanocomposite fabrication, and strain engineering, we demonstrate a reversible and chromatic mechanical response in MoS2-nanocomposites between 405 nm to 808 nm with large stress release. The chromatic mechanical response originates from the d orbitals and is related to the strength of the direct exciton resonance A and B of the few layer 2H-MoS2 affecting optical absorption and subsequent mechanical response of the nanocomposite. Applying uniaxial tensile strains to the semiconducting few-layer 2H-MoS2 crystals in the nanocomposite resulted in spatially varying energy levels inside the nanocomposite that enhanced the broadband optical absorption up to 2.3 eV and subsequent mechanical response. The unique photomechanical response in 2H-MoS2 based nanocomposites is a result of the rich d electron physics not available to nanocomposites based on sp bonded graphene and carbon nanotubes, as well as nanocomposite based on metallic nanoparticles. The reversible strain dependent optical absorption suggest applications in broad range of energy conversion technologies that is not achievable using conventional thin film semiconductors. PMID:27713550

Sleep Moderates the Association Between Response Inhibition and Self-Regulation in Early Childhood

PubMed Central

Schumacher, Allyson M.; Miller, Alison L.; Watamura, Sarah E.; Kurth, Salome; Lassonde, Jonathan M.; LeBourgeois, Monique K.

2017-01-01

Early childhood is a time of rapid developmental changes in sleep, cognitive control processes, and the regulation of emotion and behavior. This experimental study examined sleep-dependent effects on response inhibition and self-regulation, as well as whether acute sleep restriction moderated the association between these processes. Preschool children (N = 19; 45.6 ± 2.2 months; 11 female) followed a strict sleep schedule for at least 3 days before each of 2 morning behavior assessments: baseline (habitual nap/night sleep) and sleep restriction (missed nap/delayed bedtime). Response inhibition was evaluated via a go/no-go task. Twelve self-regulation strategies were coded from videotapes of children while attempting an unsolvable puzzle. We then created composite variables representing adaptive and maladaptive self-regulation strategies. Although we found no sleep-dependent effects on response inhibition or self-regulation measures, linear mixed-effects regression showed that acute sleep restriction moderated the relationship between these processes. At baseline, children with better response inhibition were more likely to use adaptive self-regulation strategies (e.g., self-talk, alternate strategies), and those with poorer response inhibition showed increased use of maladaptive self-regulation strategies (e.g., perseveration, fidgeting); however, response inhibition was not related to self-regulation strategies following sleep restriction. Our results showing a sleep-dependent effect on the associations between response inhibition and self-regulation strategies indicate that adequate sleep facilitates synergy between processes supporting optimal social-emotional functioning in early childhood. Although replication studies are needed, findings suggest that sleep may alter connections between maturing emotional and cognitive systems, which have important implications for understanding risk for or resilience to developmental psychopathology. PMID:27652491

Sleep Moderates the Association Between Response Inhibition and Self-Regulation in Early Childhood.

PubMed

Schumacher, Allyson M; Miller, Alison L; Watamura, Sarah E; Kurth, Salome; Lassonde, Jonathan M; LeBourgeois, Monique K

2017-01-01

Early childhood is a time of rapid developmental changes in sleep, cognitive control processes, and the regulation of emotion and behavior. This experimental study examined sleep-dependent effects on response inhibition and self-regulation, as well as whether acute sleep restriction moderated the association between these processes. Preschool children (N = 19; 45.6 ± 2.2 months; 11 female) followed a strict sleep schedule for at least 3 days before each of 2 morning behavior assessments: baseline (habitual nap/night sleep) and sleep restriction (missed nap/delayed bedtime). Response inhibition was evaluated via a go/no-go task. Twelve self-regulation strategies were coded from videotapes of children while attempting an unsolvable puzzle. We then created composite variables representing adaptive and maladaptive self-regulation strategies. Although we found no sleep-dependent effects on response inhibition or self-regulation measures, linear mixed-effects regression showed that acute sleep restriction moderated the relationship between these processes. At baseline, children with better response inhibition were more likely to use adaptive self-regulation strategies (e.g., self-talk, alternate strategies), and those with poorer response inhibition showed increased use of maladaptive self-regulation strategies (e.g., perseveration, fidgeting); however, response inhibition was not related to self-regulation strategies following sleep restriction. Our results showing a sleep-dependent effect on the associations between response inhibition and self-regulation strategies indicate that adequate sleep facilitates synergy between processes supporting optimal social-emotional functioning in early childhood. Although replication studies are needed, findings suggest that sleep may alter connections between maturing emotional and cognitive systems, which have important implications for understanding risk for or resilience to developmental psychopathology.

Implementation of an alert and response system in Haiti during the early stage of the response to the cholera epidemic.

PubMed

Santa-Olalla, Patricia; Gayer, Michelle; Magloire, Roc; Barrais, Robert; Valenciano, Marta; Aramburu, Carmen; Poncelet, Jean Luc; Gustavo Alonso, Juan Carlos; Van Alphen, Dana; Heuschen, Florence; Andraghetti, Roberta; Lee, Robert; Drury, Patrick; Aldighieri, Sylvain

2013-10-01

The start of the cholera epidemic in Haiti quickly highlighted the necessity of the implementation of an Alert and Response (A&R) System to complement the existing national surveillance system. The national system had been able to detect and confirm the outbreak etiology but required external support to monitor the spread of cholera and coordinate response, because much of the information produced was insufficiently timely for real-time monitoring and directing of a rapid, targeted response. The A&R System was designed by the Pan American Health Organization/World Health Organization in collaboration with the Haiti Ministry of Health, and it was based on a network of partners, including any institution, structure, or individual that could identify, verify, and respond to alerts. The defined objectives were to (1) save lives through early detection and treatment of cases and (2) control the spread through early intervention at the community level. The operational structure could be broken down into three principle categories: (1) alert (early warning), (2) verification and assessment of the information, and (3) efficient and timely response in coordination with partners to avoid duplication. Information generated by the A&R System was analyzed and interpreted, and the qualitative information was critical in qualifying the epidemic and defining vulnerable areas, particularly because the national surveillance system reported incomplete data for more than one department. The A&R System detected a number of alerts unrelated to cholera and facilitated rapid access to that information. The sensitivity of the system and its ability to react quickly was shown in May of 2011, when an abnormal increase in alerts coming from several communes in the Sud-Est Department in epidemiological weeks (EWs) 17 and 18 were noted and disseminated network-wide and response activities were implemented. The national cholera surveillance system did not register the increase until EWs 21 and

Implementation of an Alert and Response System in Haiti during the Early Stage of the Response to the Cholera Epidemic

PubMed Central

Santa-Olalla, Patricia; Gayer, Michelle; Magloire, Roc; Barrais, Robert; Valenciano, Marta; Aramburu, Carmen; Poncelet, Jean Luc; Gustavo Alonso, Juan Carlos; Van Alphen, Dana; Heuschen, Florence; Andraghetti, Roberta; Lee, Robert; Drury, Patrick; Aldighieri, Sylvain

2013-01-01

The start of the cholera epidemic in Haiti quickly highlighted the necessity of the implementation of an Alert and Response (A&R) System to complement the existing national surveillance system. The national system had been able to detect and confirm the outbreak etiology but required external support to monitor the spread of cholera and coordinate response, because much of the information produced was insufficiently timely for real-time monitoring and directing of a rapid, targeted response. The A&R System was designed by the Pan American Health Organization/World Health Organization in collaboration with the Haiti Ministry of Health, and it was based on a network of partners, including any institution, structure, or individual that could identify, verify, and respond to alerts. The defined objectives were to (1) save lives through early detection and treatment of cases and (2) control the spread through early intervention at the community level. The operational structure could be broken down into three principle categories: (1) alert (early warning), (2) verification and assessment of the information, and (3) efficient and timely response in coordination with partners to avoid duplication. Information generated by the A&R System was analyzed and interpreted, and the qualitative information was critical in qualifying the epidemic and defining vulnerable areas, particularly because the national surveillance system reported incomplete data for more than one department. The A&R System detected a number of alerts unrelated to cholera and facilitated rapid access to that information. The sensitivity of the system and its ability to react quickly was shown in May of 2011, when an abnormal increase in alerts coming from several communes in the Sud-Est Department in epidemiological weeks (EWs) 17 and 18 were noted and disseminated network-wide and response activities were implemented. The national cholera surveillance system did not register the increase until EWs 21 and

Genetic and transcriptomic analyses provide new insights on the early antiviral response to VHSV in resistant and susceptible rainbow trout.

PubMed

Verrier, Eloi R; Genet, Carine; Laloë, Denis; Jaffrezic, Florence; Rau, Andrea; Esquerre, Diane; Dechamp, Nicolas; Ciobotaru, Céline; Hervet, Caroline; Krieg, Francine; Jouneau, Luc; Klopp, Christophe; Quillet, Edwige; Boudinot, Pierre

2018-06-19

The viral hemorrhagic septicemia virus (VHSV) is a major threat for salmonid farming and for wild fish populations worldwide. Previous studies have highlighted the importance of innate factors regulated by a major quantitative trait locus (QTL) for the natural resistance to waterborne VHSV infection in rainbow trout. The aim of this study was to analyze the early transcriptomic response to VHSV inoculation in cell lines derived from previously described resistant and susceptible homozygous isogenic lines of rainbow trout to obtain insights into the molecular mechanisms responsible for the resistance to the viral infection. We first confirmed the presence of the major QTL in a backcross involving a highly resistant fish isogenic line (B57) and a highly susceptible one (A22), and were able to define the confidence interval of the QTL and to identify its precise position. We extended the definition of the QTL since it controls not only resistance to waterborne infection but also the kinetics of mortality after intra-peritoneal injection. Deep sequencing of the transcriptome of B57 and A22 derived cell lines exposed to inactivated VHSV showed a stronger response to virus inoculation in the resistant background. In line with our previous observations, an early and strong induction of interferon and interferon-stimulated genes was correlated with the resistance to VHSV, highlighting the major role of innate immune factors in natural trout resistance to the virus. Interestingly, major factors of the antiviral innate immunity were much more expressed in naive B57 cells compared to naive A22 cells, which likely contributes to the ability of B57 to mount a fast antiviral response after viral infection. These observations were further extended by the identification of several innate immune-related genes localized close to the QTL area on the rainbow trout genome. Taken together, our results improve our knowledge in virus-host interactions in vertebrates and provide novel

A dominant bursting electromyograph pattern in dystonic conditions predicts an early response to pallidal stimulation.

PubMed

Yianni, John; Wang, Shou Yan; Liu, Xuguang; Bain, Peter G; Nandi, Dipankar; Gregory, Ralph; Joint, Carole; Stein, John F; Aziz, Tipu Z

2006-08-01

Although chronic pallidal deep brain stimulation (DBS) is effective in the treatment of medically intractable dystonia, there is no way of predicting the variations in clinical outcome, partly due to our limited understanding of the pathophysiological mechanisms underlying this condition. We recorded electromyographic (EMG) activity from the most severely affected muscle groups in seven dystonia patients before and after pallidal DBS. Patient EMG recordings could be classified into two groups: one consisting of patients who at rest demonstrated a dominant low frequency component of activity on power spectral analysis (ranging from 2 to 5 Hz), and one group in which this dominant pattern was absent. Early postoperative improvements (within 2-3 days) were observed in the former group, whereas the latter group benefited more gradually (over several months). Analysis of EMG activity may provide a sensitive means of identifying dystonic patients who are likely to be most responsive to functional neurosurgical intervention.

Expression of putative immune response genes during early ontogeny in the coral Acropora millepora.

PubMed

Puill-Stephan, Eneour; Seneca, François O; Miller, David J; van Oppen, Madeleine J H; Willis, Bette L

2012-01-01

Corals, like many other marine invertebrates, lack a mature allorecognition system in early life history stages. Indeed, in early ontogeny, when corals acquire and establish associations with various surface microbiota and dinoflagellate endosymbionts, they do not efficiently distinguish between closely and distantly related individuals from the same population. However, very little is known about the molecular components that underpin allorecognition and immunity responses or how they change through early ontogeny in corals. Patterns in the expression of four putative immune response genes (apextrin, complement C3, and two CELIII type lectin genes) were examined in juvenile colonies of Acropora millepora throughout a six-month post-settlement period using quantitative real-time PCR (qPCR). Expression of a CELIII type lectin gene peaked in the fourth month for most of the coral juveniles sampled and was significantly higher at this time than at any other sampling time during the six months following settlement. The timing of this increase in expression levels of putative immune response genes may be linked to allorecognition maturation which occurs around this time in A. millepora. Alternatively, the increase may represent a response to immune challenges, such as would be involved in the recognition of symbionts (such as Symbiodinium spp. or bacteria) during winnowing processes as symbioses are fine-tuned. Our data, although preliminary, are consistent with the hypothesis that lectins may play an important role in the maturation of allorecognition responses in corals. The co-expression of lectins with apextrin during development of coral juveniles also raises the possibility that these proteins, which are components of innate immunity in other invertebrates, may influence the innate immune systems of corals through a common pathway or system. However, further studies investigating the expression of these genes in alloimmune-challenged corals are needed to further

Prenatal and Early Postnatal Odorant Exposure Heightens Odor-Evoked Mitral Cell Responses in the Mouse Olfactory Bulb

PubMed Central

2017-01-01

Abstract Early sensory experience shapes the anatomy and function of sensory circuits. In the mouse olfactory bulb (OB), prenatal and early postnatal odorant exposure through odorized food (food/odorant pairing) not only increases the volume of activated glomeruli but also increases the number of mitral and tufted cells (M/TCs) connected to activated glomeruli. Given the importance of M/TCs in OB output and in mediating lateral inhibitory networks, increasing the number of M/TCs connected to a single glomerulus may significantly change odorant representation by increasing the total output of that glomerulus and/or by increasing the strength of lateral inhibition mediated by cells connected to the affected glomerulus. Here, we seek to understand the functional impact of this long-term odorant exposure paradigm on the population activity of mitral cells (MCs). We use viral expression of GCaMP6s to examine odor-evoked responses of MCs following prenatal and early postnatal odorant exposure to two dissimilar odorants, methyl salicylate (MS) and hexanal, which are both strong activators of glomeruli on the dorsal OB surface. Previous work suggests that odor familiarity may decrease odor-evoked MC response in rodents. However, we find that early food-based odorant exposure significantly changes MC responses in an unexpected way, resulting in broad increases in the amplitude, number, and reliability of excitatory MC responses across the dorsal OB. PMID:28955723

Structural effects on mechanical response of MoS2 nanostructures during compression

NASA Astrophysics Data System (ADS)

Bucholz, Eric W.; Sinnott, Susan B.

2013-07-01

In recent years, inorganic nanostructures, such as fullerene-like MoS2 and WS2 nanoparticles, have been shown to be promising candidates for friction and wear reduction in tribological applications. However, it has been demonstrated experimentally that the mechanical response of any given inorganic nanostructure varies depending on its individual structural characteristics such as size, shape, and crystallinity. Here, classical molecular dynamics simulations are performed that investigate the mechanical responses of different types of MoS2 nanostructures during uniaxial compression. The results illustrate the dependence of mechanical behavior on nanoparticle structure and, in particular, indicate that the mechanical properties of MoS2 nanostructures vary significantly with changes in the orientation of the MoS2 walls at the interface.

Maternal buffering beyond glucocorticoids: impact of early life stress on corticolimbic circuits that control infant responses to novelty

PubMed Central

Howell, Brittany R.; McMurray, Matthew S.; Guzman, Dora B.; Nair, Govind; Shi, Yundi; McCormack, Kai M.; Hu, Xiaoping; Styner, Martin A.; Sanchez, Mar M.

2017-01-01

Maternal presence has a potent buffering effect on infant fear and stress responses in primates. We previously reported that maternal presence is not effective in buffering the endocrine stress response in infant rhesus monkeys reared by maltreating mothers. We have also reported that maltreating mothers show low maternal responsiveness and permissiveness/secure-base behavior. Although still not understood, it is possible that this maternal buffering effect is mediated, at least partially, through deactivation of amygdala response circuits when mothers are present. Here we studied rhesus monkey infants that differed in the quality of early maternal care to investigate how this early experience modulated maternal buffering effects on behavioral responses to novelty during the weaning period. We also examined the relationship between these behavioral responses and structural connectivity in one of the underlying regulatory neural circuits: amygdala-prefrontal pathways. Our findings suggest that infant exploration in a novel situation is predicted by maternal responsiveness and structural integrity of amygdala-prefrontal white matter depending on maternal presence (positive relationships when mother is absent). These results provide evidence that maternal buffering of infant behavioral inhibition is dependent on the quality of maternal care and structural connectivity of neural pathways that are sensitive to early life stress. PMID:27295326

Early Response to treatment in Eating Disorders: A Systematic Review and a Diagnostic Test Accuracy Meta-Analysis.

PubMed

Nazar, Bruno Palazzo; Gregor, Louise Kathrine; Albano, Gaia; Marchica, Angelo; Coco, Gianluca Lo; Cardi, Valentina; Treasure, Janet

2017-03-01

Early response to eating disorders treatment is thought to predict a later favourable outcome. A systematic review of the literature and meta-analyses examined the robustness of this concept. The criteria used across studies to define early response were summarised following the Preferred Reporting Items for Systematic Reviews and Meta-Analyses guidelines. Diagnostic Test Accuracy methodology was used to estimate the size of the effect. Findings from 24 studies were synthesized and data from 14 studies were included in the meta-analysis. In Anorexia Nervosa, the odds ratio of early response predicting remission was 4.85(95%CI: 2.94-8.01) and the summary Area Under the Curve (AUC) = .77. In Bulimia Nervosa, the odds ratio was 2.75(95%CI:1.24-6.09) and AUC = .67. For Binge Eating Disorder, the odds ratio was 5.01(95%CI: 3.38-7.42) and AUC = .71. Early behaviour change accurately predicts later symptom remission for Anorexia Nervosa and Binge Eating Disorder but there is less predictive accuracy for Bulimia Nervosa. Copyright © 2016 John Wiley & Sons, Ltd and Eating Disorders Association. Copyright © 2016 John Wiley & Sons, Ltd and Eating Disorders Association.

Understanding Mechanical Response of Elastomeric Graphene Networks

PubMed Central

Ni, Na; Barg, Suelen; Garcia-Tunon, Esther; Macul Perez, Felipe; Miranda, Miriam; Lu, Cong; Mattevi, Cecilia; Saiz, Eduardo

2015-01-01

Ultra-light porous networks based on nano-carbon materials (such as graphene or carbon nanotubes) have attracted increasing interest owing to their applications in wide fields from bioengineering to electrochemical devices. However, it is often difficult to translate the properties of nanomaterials to bulk three-dimensional networks with a control of their mechanical properties. In this work, we constructed elastomeric graphene porous networks with well-defined structures by freeze casting and thermal reduction, and investigated systematically the effect of key microstructural features. The porous networks made of large reduced graphene oxide flakes (>20 μm) are superelastic and exhibit high energy absorption, showing much enhanced mechanical properties than those with small flakes (<2 μm). A better restoration of the graphitic nature also has a considerable effect. In comparison, microstructural differences, such as the foam architecture or the cell size have smaller or negligible effect on the mechanical response. The recoverability and energy adsorption depend on density with the latter exhibiting a minimum due to the interplay between wall fracture and friction during deformation. These findings suggest that an improvement in the mechanical properties of porous graphene networks significantly depend on the engineering of the graphene flake that controls the property of the cell walls. PMID:26348898

Response to various periods of mechanical stimuli in Physarum plasmodium

NASA Astrophysics Data System (ADS)

Umedachi, Takuya; Ito, Kentaro; Kobayashi, Ryo; Ishiguro, Akio; Nakagaki, Toshiyuki

2017-06-01

Response to mechanical stimuli is a fundamental and critical ability for living cells to survive in hazardous conditions or to form adaptive and functional structures against force(s) from the environment. Although this ability has been extensively studied by molecular biology strategies, it is also important to investigate the ability from the viewpoint of biological rhythm phenomena so as to reveal the mechanisms that underlie these phenomena. Here, we use the plasmodium of the true slime mold Physarum polycephalum as the experimental system for investigating this ability. The plasmodium was repetitively stretched for various periods during which its locomotion speed was observed. Since the plasmodium has inherent oscillation cycles of protoplasmic streaming and thickness variation, how the plasmodium responds to various periods of external stretching stimuli can shed light on the other biological rhythm phenomena. The experimental results show that the plasmodium exhibits response to periodic mechanical stimulation and changes its locomotion speed depending on the period of the stretching stimuli.

The effect of glycation on arterial microstructure and mechanical response.

PubMed

Stephen, Elizabeth A; Venkatasubramaniam, Arundhathi; Good, Theresa A; Topoleski, L D T

2014-08-01

Like engineered materials, an artery's biomechanical behavior and function depend on its microstructure. Glycation is associated with both normal aging and diabetes and has been shown to increase arterial stiffness. In this study we examined the direct effect of glycation on the mechanical response of intact arteries and on the mechanical response and structure of elastin isolated from the arteries. Samples of intact arteries and isolated elastin were prepared from porcine aortas and glycated. The mechanical response of all samples was completed using a uniaxial material test system. Glycation levels were measured using ELISA. A confocal microscope was used to image differences in the structure of the glycated and untreated elastin fibers. We found that, under the conditions used in this study, glycation led to decreased stiffness of elastin isolated from arteries, which was associated with a thinning of elastin fibers as imaged by confocal microscopy. We observed no effect of glycation on collagen fibers under our treatment conditions. These results suggest that glycation leads to weakening of the elastin component of arteries that could contribute to vascular defects seen in diabetes and aging. Prevention of glycation reactions may be an important consideration for vascular health later in life. © 2013 Wiley Periodicals, Inc.

Biological mechanisms of non-linear dose-response for respirable mineral fibers.

PubMed

Cox, Louis Anthony Tony

2018-06-19

Sufficiently high and prolonged inhalation exposures to some respirable elongated mineral particles (REMPs), notably including amphibole asbestos fibers, can increase risk of inflammation-mediated diseases including malignant mesothelioma, pleural diseases, fibrosis, and lung cancer. Chronic inflammation involves ongoing activation of the NLRP3 inflammasome, which enables immune cells to produce potent proinflammatory cytokines IL-1β and IL-18. Reactive oxygen species (ROS) (in particular, mitochondrial ROS) contribute to NRLP3 activation via a well-elucidated mechanism involving oxidation of reduced thioredoxin and association of thioredoxin-interacting protein with NLRP3. Lysosomal destabilization, efflux of cytosolic potassium ions and influx of calcium ions, signals from damaged mitochondria, both translational and post-translational controls, and prion-like polymerization have increasingly clear roles in regulating NLRP3 activation. As the molecular biology of inflammation-mediated responses to REMP exposure becomes clearer, a practical question looms: What do these mechanisms imply for the shape of the dose-response function relating exposure concentrations and durations for EMPs to risk of pathological responses? Dose-response thresholds or threshold-like nonlinearities can arise from (a) Cooperativity in assembly of supramolecular signaling complexes; (b) Positive feedback loops and bistability in regulatory networks; (c) Overwhelming of defensive barriers maintaining homeostasis; and (d) Damage thresholds, as in lysosome destabilization-induced activation of NLRP3. Each of these mechanisms holds for NLRP3 activation in response to stimuli such as REMP exposures. It is therefore timely to consider the implications of these advances in biological understanding for human health risk assessment with dose-response thresholds. Copyright © 2018. Published by Elsevier Inc.

Post-conditioning preserves glycolytic ATP during early reperfusion: a survival mechanism for the reperfused heart.

PubMed

Correa, Francisco; García, Noemí; Gallardo-Pérez, Juan; Carreno-Fuentes, Liliana; Rodríguez-Enríquez, Sara; Marín-Hernández, Alvaro; Zazueta, Cecilia

2008-01-01

Glycolytic activity during the transition period from anaerobic to aerobic metabolism has been demonstrated to be critical for heart recovery in isolated reperfused hearts. The purpose of this work was to investigate the relevance of the glycolytic pathway in preserving the cardiac function of post-conditioned hearts. The activation of the glycolytic pathway in post-conditioned hearts was evaluated by measuring GLUT-4 insertion, glucose consumption and lactate production. Iodoacetic acid and 2-deoxy-D-glucose were administrated to the working hearts to evaluate the effect of glycolytic inhibition in the post-conditioning protective effect. Post-conditioning maneuvers applied to isolated rat hearts, after prolonged ischemia and before reperfusion, promoted recovery of cardiac mechanical function with sustained increase of GLUT-4 translocation and activation of the glycolytic pathway during ischemia and early reperfusion. Iodoacetate inhibited the protective effect of post-conditioning, without affecting the mitochondrial oxidative capacity. Glycolysis contribution to maintain mechanical function at early reperfusion was observed in post-conditioned hearts perfused with 2-deoxy-D-glucose and in hearts in which iodoacetate was administered only during reperfusion. It is concluded that in the post-conditioned heart, a functional compartmentation of anaerobic energy metabolism, at early reperfusion, plays a significant role in cardiac protection against reperfusion damage. Copyright 2008 S. Karger AG, Basel.

EF5 PET of Tumor Hypoxia: A Predictive Imaging Biomarker of Response to Stereotactic Ablative Radiotherapy (SABR) for Early Lung Cancer

DTIC Science & Technology

2014-09-01

Predictive Imaging Biomarker of Response to Stereotactic Ablative Radiotherapy ( SABR ) for Early Lung Cancer PRINCIPAL INVESTIGATOR: Billy W...CONTRACT NUMBER Response to Stereotactic Ablative Radiotherapy ( SABR ) for Early Lung Cancer 5b. GRANT NUMBER W81XWH-12-1-0236 5c...NOTES 14. ABSTRACT Purpose and scope: Stereotactic ablative radiotherapy ( SABR ) has become a new standard of care for early stage lung

Observations on the responses of muscle to mechanical and electrical stimuli

PubMed Central

Meadows, J. C.

1971-01-01

Responses to mechanical and electrical stimuli have been studied in vastus medialis in four young adults. Percussion causes an immediate, brief contraction in those muscle fibres passing beneath the site of the blow. This is accompanied by EMG activity which is propagated along the muscle fibres at a normal velocity of around 4 m/sec. The EMG activity lasts much longer than that produced by a single electrical stimulus to muscle fibres because repetitive firing occurs in some of the muscle fibres activated mechanically. This response to percussion is unaffected by nerve blockade with 2% xylocaine. Percussion close to the motor point may cause delayed fasciculation due to activation of intramuscular motor nerve fibres. This, too, is unaffected by nerve blockade. Some observations on EMG insertional activity provoked by needle movement are reported. It is concluded that muscle has a basic tendency to discharge repetitively when stimulated by mechanical means and that EMG insertional activity and the EMG response to percussion reported in this paper are both manifestations of this same tendency, which is increased in the myotonias. Images PMID:4251668

Early nongenomic events in aldosterone action in renal collecting duct cells: PKCalpha activation, mineralocorticoid receptor phosphorylation, and cross-talk with the genomic response.

PubMed

Le Moëllic, Cathy; Ouvrard-Pascaud, Antoine; Capurro, Claudia; Cluzeaud, Francoise; Fay, Michel; Jaisser, Frederic; Farman, Nicolette; Blot-Chabaud, Marcel

2004-05-01

Effects of aldosterone on its target cells have long been considered to be mediated exclusively through the genomic pathway; however, evidence has been provided for rapid effects of the hormone that may involve nongenomic mechanisms. Whether an interaction exists between these two signaling pathways is not yet established. In this study, the authors show that aldosterone triggers both early nongenomic and late genomic increase in sodium transport in the RCCD(2) rat cortical collecting duct cell line. In these cells, the early (up to 2.5 h) aldosterone-induced increase in short-circuit current (Isc) is not blocked by the mineralocorticoid receptor (MR) antagonist RU26752, it does not require mRNA or protein synthesis, and it involves the PKCalpha signaling pathway. In addition, this early response is reproduced by aldosterone-BSA, which acts at the cell surface and presumably does not enter the cells (aldo-BSA is unable to trigger the late response). The authors also show that MR is rapidly phosphorylated on serine and threonine residues by aldosterone or aldosterone-BSA. In contrast, the late (4 to 24 h) aldosterone-induced increase in ion transport occurs through activation of the MR and requires mRNA and protein synthesis. Interestingly, nongenomic and genomic aldosterone actions appear to be interdependent. Blocking the PKCalpha pathway results in the inhibition of the late genomic response to aldosterone, as demonstrated by the suppression of aldosterone-induced increase in MR transactivation activity, alpha1 Na(+)/K(+)/ATPase mRNA, and Isc. These data suggest cross-talk between the nongenomic and genomic responses to aldosterone in renal cells and suggest that the aldosterone-MR mediated increase in mRNA/protein synthesis and ion transport depends, at least in part, upon PKCalpha activation. E-mail: marcel.blot-chabaud@pharmacie.univ-mrs.fr

The impact of Early Warning Score and Rapid Response Systems on nurses' competence: An integrative literature review and synthesis.

PubMed

Jensen, Jørghild Karlotte; Skår, Randi; Tveit, Bodil

2018-04-01

To describe, interpret and synthesise the current research findings on the impact of the Early Warning Score and Rapid Response Systems on nurses' competence in identifying and managing deteriorating patients in general hospital wards. As patient safety initiatives designed to ensure the early identification and management of deteriorating patients, the Early Warning Score and Rapid Response Systems have broad appeal. However, it is still unclear how these systems impact nurses' competence when these systems are used in general hospital wards. CINAHL, PubMed, Cochrane, EMBASE and Ovid MEDLINE databases were systematically searched for relevant articles. Articles were appraised, a thematic analysis was conducted, and similar and divergent perspectives on emergent themes and subthemes were extracted by a team of researchers. Thirty-six studies met the inclusion criteria. The analysis of findings showed how the Early Warning Score and Rapid Response Systems impacted three competence areas: (i) Nurses' competence in assessing and caring for patients related to the subthemes: (a) sensing clinical deterioration and (b) the development of skills and knowledge. (ii). Nurses' competence in referring patients, related to the subthemes: (a) deciding whether to summon help and (b) the language and communication lines in the referral process. (ii) Nurses' coping and mastery experiences. The impact of the Early Warning Score and Rapid Response Systems on nurses' competence in identifying and managing deteriorating patients is beneficial but also somewhat contradictory. A greater understanding of nurses' development of competence when using the Early Warning Score and Rapid Response Systems will facilitate the design of implementation strategies and the use of these systems to improve practice. © 2017 John Wiley & Sons Ltd.

Monitoring in real-time focal adhesion protein dynamics in response to a discrete mechanical stimulus

NASA Astrophysics Data System (ADS)

von Bilderling, Catalina; Caldarola, Martín; Masip, Martín E.; Bragas, Andrea V.; Pietrasanta, Lía I.

2017-01-01

The adhesion of cells to the extracellular matrix is a hierarchical, force-dependent, multistage process that evolves at several temporal scales. An understanding of this complex process requires a precise measurement of forces and its correlation with protein responses in living cells. We present a method to quantitatively assess live cell responses to a local and specific mechanical stimulus. Our approach combines atomic force microscopy with fluorescence imaging. Using this approach, we evaluated the recruitment of adhesion proteins such as vinculin, focal adhesion kinase, paxillin, and zyxin triggered by applying forces in the nN regime to live cells. We observed in real time the development of nascent adhesion sites, evident from the accumulation of early adhesion proteins at the position where the force was applied. We show that the method can be used to quantify the recruitment characteristic times for adhesion proteins in the formation of focal complexes. We also found a spatial remodeling of the mature focal adhesion protein zyxin as a function of the applied force. Our approach allows the study of a variety of complex biological processes involved in cellular mechanotransduction.

Monitoring in real-time focal adhesion protein dynamics in response to a discrete mechanical stimulus.

PubMed

von Bilderling, Catalina; Caldarola, Martín; Masip, Martín E; Bragas, Andrea V; Pietrasanta, Lía I

2017-01-01

The adhesion of cells to the extracellular matrix is a hierarchical, force-dependent, multistage process that evolves at several temporal scales. An understanding of this complex process requires a precise measurement of forces and its correlation with protein responses in living cells. We present a method to quantitatively assess live cell responses to a local and specific mechanical stimulus. Our approach combines atomic force microscopy with fluorescence imaging. Using this approach, we evaluated the recruitment of adhesion proteins such as vinculin, focal adhesion kinase, paxillin, and zyxin triggered by applying forces in the nN regime to live cells. We observed in real time the development of nascent adhesion sites, evident from the accumulation of early adhesion proteins at the position where the force was applied. We show that the method can be used to quantify the recruitment characteristic times for adhesion proteins in the formation of focal complexes. We also found a spatial remodeling of the mature focal adhesion protein zyxin as a function of the applied force. Our approach allows the study of a variety of complex biological processes involved in cellular mechanotransduction.

Intracranial baroreflex yielding an early cushing response in human.

PubMed

Schmidt, E A; Czosnyka, Z; Momjian, S; Czosnyka, M; Bech, R A; Pickard, J D

2005-01-01

The Cushing response is a pre-terminal sympatho-adrenal systemic response to very high ICP. Animal studies have demonstrated that a moderate rise of ICP yields a reversible pressure-mediated systemic response. Infusion studies are routine procedures to investigate, by infusing CSF space with saline, the cerebrospinal fluid (CSF) biophysics in patients suspected of hydrocephalus. Our study aims at assessing systemic and cerebral haemodynamic changes during moderate rise of ICP in human. Infusion studies were performed in 34 patients. This is a routine test perform in patients presenting with symptoms of NPH during their pre-shunting assessment. Arterial blood pressure (ABP) and cerebral blood flow velocity (FV) were non-invasively monitored with photoplethysmography and transcranial Doppler. The rise in ICP (8.2 +/- 5.1 mmHg to 25 +/- 8.3 mmHg) was followed by a significant rise in ABP (106.6 +/- 29.7 mmHg to 115.2 +/- 30.1 mmHg), drop in CPP (98.3 +/- 29 mmHg to 90.2 +/- 30.7 mmHg) and decrease in FV (55.6 +/- 17 cm/s to 51.1 +/- 16.3 cm/s). Increasing ICP did not alter heart rate (70.4 +/- 10.4/min to 70.3 +/- 9.1/min) but augmented the heart rate variance (0.046 +/- 0.058 to 0.067 +/- 0.075/min). In a population suspected of hydrocephalus, our study demonstrated that a moderate rise of ICP yields a reversible pressure-mediated systemic response, demonstrating an early Cushing response in human and a putative intracranial baroreflex.

Determinants of motion response anisotropies in human early visual cortex: the role of configuration and eccentricity.

PubMed

Maloney, Ryan T; Watson, Tamara L; Clifford, Colin W G

2014-10-15

Anisotropies in the cortical representation of various stimulus parameters can reveal the fundamental mechanisms by which sensory properties are analysed and coded by the brain. One example is the preference for motion radial to the point of fixation (i.e. centripetal or centrifugal) exhibited in mammalian visual cortex. In two experiments, this study used functional magnetic resonance imaging (fMRI) to explore the determinants of these radial biases for motion in functionally-defined areas of human early visual cortex, and in particular their dependence upon eccentricity which has been indicated in recent reports. In one experiment, the cortical response to wide-field random dot kinematograms forming 16 different complex motion patterns (including centrifugal, centripetal, rotational and spiral motion) was measured. The response was analysed according to preferred eccentricity within four different eccentricity ranges. Response anisotropies were characterised by enhanced activity for centripetal or centrifugal patterns that changed systematically with eccentricity in visual areas V1-V3 and hV4 (but not V3A/B or V5/MT+). Responses evolved from a preference for centrifugal over centripetal patterns close to the fovea, to a preference for centripetal over centrifugal at the most peripheral region stimulated, in agreement with previous work. These effects were strongest in V2 and V3. In a second experiment, the stimuli were restricted to within narrow annuli either close to the fovea (0.75-1.88°) or further in the periphery (4.82-6.28°), in a way that preserved the local motion information available in the first experiment. In this configuration a preference for radial motion (centripetal or centrifugal) persisted but the dependence upon eccentricity disappeared. Again this was clearest in V2 and V3. A novel interpretation of the dependence upon eccentricity of motion anisotropies in early visual cortex is offered that takes into account the spatiotemporal

Infusing Culturally Responsive Science Curriculum into Early Childhood Teacher Preparation

NASA Astrophysics Data System (ADS)

Yoon, Jiyoon; Martin, Leisa A.

2017-08-01

Previous research studies in early childhood teacher education have indicated that teacher candidates are not adequately prepared to demonstrate the knowledge and skills needed to teach science to all children including culturally and linguistically diverse students. To address this issue, the researchers provided 31 early childhood teacher candidates with instructions through a culturally responsive science education curriculum that integrates American and Korean science curriculum corresponding to the American and Korean standards for teacher education. The results showed a statistically significant increase in their Personal Science Teaching Efficacy (PSTE). In addition, the teacher candidates were able to create a multicultural/diverse lesson in the developing and proficiency levels based on Ambrosio's lesson matrix. This study provides teacher candidates' knowledge as well as an additional resource for developing their self-efficacy and understanding the role of multicultural/diverse lesson planning for science instruction. Also, teacher candidates could be better prepared by understanding how other countries approach science education and integrating this knowledge to enrich their own science instruction.

Prognosis and response to laser treatment of early-onset hypertrophic port-wine stains (PWS).

PubMed

Passeron, Thierry; Salhi, Aicha; Mazer, Jean-Michel; Lavogiez, Céline; Mazereeuw-Hautier, Juliette; Galliot, Chrystèle; Collet-Villette, Anne-Marie; Labreze, Christine; Boon, Laurence; Hardy, Jean-Philippe; Fayard, Virginie; Livideanu, Cristina Bulai; Toubel, Gérard; Georgescou, Gabriela; Gral, Nathalie; Maza, Aude; Lacour, Jean-Philippe

2016-07-01

There is limited information regarding early development of soft-tissue and/or bone hypertrophy with facial port-wine stains (PWS). We sought to characterize patients with hypertrophic PWS presenting during childhood. Patients with a facial PWS and underlying hypertrophy that developed before the age of 18 years were included in a multicenter retrospective study. Age at onset of the hypertrophy, its location, association with odontologic problems, presence of other associated complications, and response to laser treatment were recorded. A total of 98 patients were included. The mean age at onset of hypertrophy, retrieved for 77 of 98 patients, was 5.6 years. The hypertrophy was congenital in 26%. Odontologic problems were noted in 39.8% of cases. Other complications, including cataract, asymmetric development of the maxillary bone, and speech delay/disorders, were reported in 18.4%. In all, 67 patients received laser treatment. Only 3% achieved complete or nearly complete clearance of the PWS. As only cases of PWS with early-onset hypertrophy were included, we were unable to calculate the prevalence of this manifestation. PWS with early-onset hypertrophy are associated with a high rate of complications and a poor response to laser treatment. Periodic monitoring is recommended for early detection and treatment of complications. Copyright © 2016 American Academy of Dermatology, Inc. Published by Elsevier Inc. All rights reserved.

Inositol polyphosphate multikinase is a coactivator for serum response factor-dependent induction of immediate early genes

PubMed Central

Kim, Eunha; Tyagi, Richa; Lee, Joo-Young; Park, Jina; Kim, Young-ran; Beon, Jiyoon; Chen, Po Yu; Cha, Jiyoung Y.; Snyder, Solomon H.; Kim, Seyun

2013-01-01

Inositol polyphosphate multikinase (IPMK) is a notably pleiotropic protein. It displays both inositol phosphate kinase and phosphatidylinositol kinase catalytic activities. Noncatalytically, IPMK stabilizes the mammalian target of rapamycin complex 1 and acts as a transcriptional coactivator for CREB-binding protein/E1A binding protein p300 and tumor suppressor protein p53. Serum response factor (SRF) is a major transcription factor for a wide range of immediate early genes. We report that IPMK, in a noncatalytic role, is a transcriptional coactivator for SRF mediating the transcription of immediate early genes. Stimulation by serum of many immediate early genes is greatly reduced by IPMK deletion. IPMK stimulates expression of these genes, an influence also displayed by catalytically inactive IPMK. IPMK acts by binding directly to SRF and thereby enhancing interactions of SRF with the serum response element of diverse genes. PMID:24248338

A Model to Study Articular Cartilage Mechanical and Biological Responses to Sliding Loads.

PubMed

Schätti, Oliver R; Gallo, Luigi M; Torzilli, Peter A

2016-08-01

In physiological conditions, joint function involves continuously moving contact areas over the tissue surface. Such moving contacts play an important role for the durability of the tissue. It is known that in pathological joints these motion paths and contact mechanics change. Nevertheless, limited information exists on the impact of such physiological and pathophysiological dynamic loads on cartilage mechanics and its subsequent biological response. We designed and validated a mechanical device capable of applying simultaneous compression and sliding forces onto cartilage explants to simulate moving joint contact. Tests with varying axial loads (1-4 kg) and sliding speeds (1-20 mm/s) were performed on mature viable bovine femoral condyles to investigate cartilage mechanobiological responses. High loads and slow sliding speeds resulted in highest cartilage deformations. Contact stress and effective cartilage moduli increased with increasing load and increasing speed. In a pilot study, changes in gene expression of extracellular matrix proteins were correlated with strain, contact stress and dynamic effective modulus. This study describes a mechanical test system to study the cartilage response to reciprocating sliding motion and will be helpful in identifying mechanical and biological mechanisms leading to the initiation and development of cartilage degeneration.

How the nucleus and mitochondria communicate in energy production during stress: nuclear MtATP6, an early-stress responsive gene, regulates the mitochondrial F₁F₀-ATP synthase complex.

PubMed

Moghadam, Ali Asghar; Ebrahimie, Eemaeil; Taghavi, Seyed Mohsen; Niazi, Ali; Babgohari, Mahbobeh Zamani; Deihimi, Tahereh; Djavaheri, Mohammad; Ramezani, Amin

2013-07-01

A small number of stress-responsive genes, such as those of the mitochondrial F1F0-ATP synthase complex, are encoded by both the nucleus and mitochondria. The regulatory mechanism of these joint products is mysterious. The expression of 6-kDa subunit (MtATP6), a relatively uncharacterized nucleus-encoded subunit of F0 part, was measured during salinity stress in salt-tolerant and salt-sensitive cultivated wheat genotypes, as well as in the wild wheat genotypes, Triticum and Aegilops using qRT-PCR. The MtATP6 expression was suddenly induced 3 h after NaCl treatment in all genotypes, indicating an early inducible stress-responsive behavior. Promoter analysis showed that the MtATP6 promoter includes cis-acting elements such as ABRE, MYC, MYB, GTLs, and W-boxes, suggesting a role for this gene in abscisic acid-mediated signaling, energy metabolism, and stress response. It seems that 6-kDa subunit, as an early response gene and nuclear regulatory factor, translocates to mitochondria and completes the F1F0-ATP synthase complex to enhance ATP production and maintain ion homeostasis under stress conditions. These communications between nucleus and mitochondria are required for inducing mitochondrial responses to stress pathways. Dual targeting of 6-kDa subunit may comprise as a mean of inter-organelle communication and save energy for the cell. Interestingly, MtATP6 showed higher and longer expression in the salt-tolerant wheat and the wild genotypes compared to the salt-sensitive genotype. Apparently, salt-sensitive genotypes have lower ATP production efficiency and weaker energy management than wild genotypes; a stress tolerance mechanism that has not been transferred to cultivated genotypes.

The Confluence of Adverse Early Experience and Puberty on the Cortisol Awakening Response

ERIC Educational Resources Information Center

Quevedo, Karina; Johnson, Anna E.; Loman, Michelle L.; LaFavor, Theresa L.; Gunnar, Megan

2012-01-01

Associations between early deprivation/neglect in the form of institutional care with the cortisol awakening response (CAR) were examined as a function of pubertal status among 12- and 13-year-old postinstitutionalized youth. CARs indexed hypothalamic-pituitary-adrenocortical reactivity. Postinstitutionalized youth were compared to youth adopted…

Amount of fear extinction changes its underlying mechanisms.

PubMed

An, Bobae; Kim, Jihye; Park, Kyungjoon; Lee, Sukwon; Song, Sukwoon; Choi, Sukwoo

2017-07-03

There has been a longstanding debate on whether original fear memory is inhibited or erased after extinction. One possibility that reconciles this uncertainty is that the inhibition and erasure mechanisms are engaged in different phases (early or late) of extinction. In this study, using single-session extinction training and its repetition (multiple-session extinction training), we investigated the inhibition and erasure mechanisms in the prefrontal cortex and amygdala of rats, where neural circuits underlying extinction reside. The inhibition mechanism was prevalent with single-session extinction training but faded when single-session extinction training was repeated. In contrast, the erasure mechanism became prevalent when single-session extinction training was repeated. Moreover, ablating the intercalated neurons of amygdala, which are responsible for maintaining extinction-induced inhibition, was no longer effective in multiple-session extinction training. We propose that the inhibition mechanism operates primarily in the early phase of extinction training, and the erasure mechanism takes over after that.

Temporally Dissociable Mechanisms of Self-Control: Early Attentional Filtering Versus Late Value Modulation

PubMed Central

Hare, Todd; Rangel, Antonio

2013-01-01

Optimal decision-making often requires exercising self-control. A growing fMRI literature has implicated the dorsolateral prefrontal cortex (dlPFC) in successful self-control, but due to the limitations inherent in BOLD measures of brain activity, the neurocomputational role of this region has not been resolved. Here we exploit the high temporal resolution and whole-brain coverage of event-related potentials (ERPs) to test the hypothesis that dlPFC affects dietary self-control through two different mechanisms: attentional filtering and value modulation. Whereas attentional filtering of sensory input should occur early in the decision process, value modulation should occur later on, after the computation of stimulus values begins. Hungry human subjects were asked to make food choices while we measured neural activity using ERP in a natural condition, in which they responded freely and did not exhibit a tendency to regulate their diet, and in a self-control condition, in which they were given a financial incentive to lose weight. We then measured various neural markers associated with the attentional filtering and value modulation mechanisms across the decision period to test for changes in neural activity during the exercise of self-control. Consistent with the hypothesis, we found evidence for top-down attentional filtering early on in the decision period (150–200 ms poststimulus onset) as well as evidence for value modulation later in the process (450–650 ms poststimulus onset). We also found evidence that dlPFC plays a role in the deployment of both mechanisms. PMID:24285897

Mechanical responses of rat vibrissae to airflow

PubMed Central

Yu, Yan S. W.; Graff, Matthew M.; Hartmann, Mitra J. Z.

2016-01-01

ABSTRACT The survival of many animals depends in part on their ability to sense the flow of the surrounding fluid medium. To date, however, little is known about how terrestrial mammals sense airflow direction or speed. The present work analyzes the mechanical response of isolated rat macrovibrissae (whiskers) to airflow to assess their viability as flow sensors. Results show that the whisker bends primarily in the direction of airflow and vibrates around a new average position at frequencies related to its resonant modes. The bending direction is not affected by airflow speed or by geometric properties of the whisker. In contrast, the bending magnitude increases strongly with airflow speed and with the ratio of the whisker's arc length to base diameter. To a much smaller degree, the bending magnitude also varies with the orientation of the whisker's intrinsic curvature relative to the direction of airflow. These results are used to predict the mechanical responses of vibrissae to airflow across the entire array, and to show that the rat could actively adjust the airflow data that the vibrissae acquire by changing the orientation of its whiskers. We suggest that, like the whiskers of pinnipeds, the macrovibrissae of terrestrial mammals are multimodal sensors – able to sense both airflow and touch – and that they may play a particularly important role in anemotaxis. PMID:27030774

Effect of early vs late tracheostomy placement on survival in patients receiving mechanical ventilation: the TracMan randomized trial.

PubMed

Young, Duncan; Harrison, David A; Cuthbertson, Brian H; Rowan, Kathy

2013-05-22

Tracheostomy is a widely used intervention in adult critical care units. There is little evidence to guide clinicians regarding the optimal timing for this procedure. To test whether early vs late tracheostomy would be associated with lower mortality in adult patients requiring mechanical ventilation in critical care units. An open multicentered randomized clinical trial conducted between 2004 and 2011 involving 70 adult general and 2 cardiothoracic critical care units in 13 university and 59 nonuniversity hospitals in the United Kingdom. Of 1032 eligible patients, 909 adult patients breathing with the aid of mechanical ventilation for less than 4 days and identified by the treating physician as likely to require at least 7 more days of mechanical ventilation. Patients were randomized 1:1 to early tracheostomy (within 4 days) or late tracheostomy (after 10 days if still indicated). The primary outcome measure was 30-day mortality and the analysis was by intention to treat. Of the 455 patients assigned to early tracheostomy, 91.9% (95% CI, 89.0%-94.1%) received a tracheostomy and of 454 assigned to late tracheostomy, 44.9% (95% CI, 40.4%-49.5%) received a tracheostomy. All-cause mortality 30 days after randomization was 30.8% (95% CI, 26.7%-35.2%) in the early and 31.5% (95% CI, 27.3%-35.9%) in the late group (absolute risk reduction for early vs late, 0.7%; 95% CI, -5.4% to 6.7%). Two-year mortality was 51.0% (95% CI, 46.4%-55.6%) in the early and 53.7% (95% CI, 49.1%-58.3%) in the late group (P = .74). Median critical care unit length of stay in survivors was 13.0 days in the early and 13.1 days in the late group (P = .74). Tracheostomy-related complications were reported for 6.3% (95% CI, 4.6%-8.5%) of patients (5.5% in the early group, 7.8% in the late group). For patients breathing with the aid of mechanical ventilation treated in adult critical care units in the United Kingdom, tracheostomy within 4 days of critical care admission was not associated with an

InteractInteraction mechanism of emergency response in geological hazard perception and risk management: a case study in Zhouqu county

NASA Astrophysics Data System (ADS)

Qi, Yuan; Zhao, Hongtao

2017-04-01

China is one of few several natural disaster prone countries, which has complex geological and geographical environment and abnormal climate. On August 8, 2010, a large debris flow disaster happened in Zhouqu Country, Gansu province, resulting in more than 1700 casualties and more than 200 buildings damaged. In order to percept landslide and debris flow, an early warning system was established in the county. Spatial information technologies, such as remote sensing, GIS, and GPS, play core role in the early warning system, due to their functions in observing, analyzing, and locating geological disasters. However, all of these spatial information technologies could play an important role only guided by the emergency response mechanism. This article takes the establishment of Zhouqu Country's Disaster Emergency Response Interaction Mechanism (DERIM) as an example to discuss the risk management of country-level administrative units. The country-level risk management aims to information sharing, resources integration, integrated prevention and unified command. Then, nine subsystems support DERIM, which included disaster prevention and emergency data collection and sharing system, joint duty system, disaster verification and evaluation system, disaster consultation system, emergency warning and information release system, emergency response system, disaster reporting system, plan management system, mass prediction and prevention management system. At last, an emergency command platform in Zhouqu Country built up to realize DERIM. The core mission of the platform consists of daily management of disaster, monitoring and warning, comprehensive analysis, information release, consultation and decision-making, emergency response, etc. Five functional modules, including module of disaster information management, comprehensive monitoring module (geological monitoring, meteorological monitoring, water conservancy and hydrological monitoring), alarm management module, emergency

Initial Weight Loss Response as an Indicator for Providing Early Rescue Efforts to Improve Long-term Treatment Outcomes.

PubMed

Unick, Jessica L; Pellegrini, Christine A; Demos, Kathryn E; Dorfman, Leah

2017-09-01

There is a large variability in response to behavioral weight loss (WL) programs. Reducing rates of obesity and diabetes may require more individuals to achieve clinically significant WL post-treatment. Given that WL within the first 1-2 months of a WL program is associated with long-term WL, it may be possible to improve treatment outcomes by identifying and providing additional intervention to those with poor initial success (i.e., "early non-responders"). We review the current literature regarding early non-response to WL programs and discuss how adaptive interventions can be leveraged as a strategy to "rescue" early non-responders. Preliminary findings suggest that adaptive interventions, specifically stepped care approaches, offer promise for improving outcomes among early non-responders. Future studies need to determine the optimal time point and threshold for intervening and the type of early intervention to employ. Clinicians and researchers should consider the discussed factors when making treatment decisions.

Piezoelectric Response of Ferroelectric Ceramics Under Mechanical Stress

DTIC Science & Technology

2015-09-17

dynamic response, and predict mechanical breakdown of electronic materials, numerous testing techniques such as very high-g machines , drop towers...James C. Hierholzer for building the custom test fixture, Michael D. Craft for his help with static capacitance measurements, Bryan J. Turner, Scott D...ISOLA 370HR Board Specimen Test Set-Up . . . . . . . . . . . . . . . . . . 59 3.3 Printed Circuit Board Electrical Layout

Local Mechanical Response of Superelastic NiTi Shape-Memory Alloy Under Uniaxial Loading

NASA Astrophysics Data System (ADS)

Xiao, Yao; Zeng, Pan; Lei, Liping; Du, Hongfei

2015-11-01

In this paper, we focus on the local mechanical response of superelastic NiTi SMA at different temperatures under uniaxial loading. In situ DIC is applied to measure the local strain of the specimen. Based on the experimental results, two types of mechanical response, which are characterized with localized phase transformation and homogenous phase transformation, are identified, respectively. Motivated by residual strain accumulation phenomenon of the superelastic mechanical response, we conduct controlled experiments, and infer that for a given material point, all (or most) of the irreversibility is accumulated when the transformation front is traversing the material point. A robust constitutive model is established to explain the experimental phenomena and we successfully simulate the evolution of local strain that agrees closely with the experimental results.

Mechanical response and buckling of a polymer simulation model of the cell nucleus

NASA Astrophysics Data System (ADS)

Banigan, Edward; Stephens, Andrew; Marko, John

The cell nucleus must robustly resist extra- and intracellular forces to maintain genome architecture. Micromanipulation experiments measuring nuclear mechanical response reveal that the nucleus has two force response regimes: a linear short-extension response due to the chromatin interior and a stiffer long-extension response from lamin A, comprising the intermediate filament protein shell. To explain these results, we developed a quantitative simulation model with realistic parameters for chromatin and the lamina. Our model predicts that crosslinking between chromatin and the lamina is essential for responding to small strains and that changes to the interior topological organization can alter the mechanical response of the whole nucleus. Thus, chromatin polymer elasticity, not osmotic pressure, is the dominant regulator of this force response. Our model reveals a novel buckling transition for polymer shells: as force increases, the shell buckles transverse to the applied force. This transition, which arises from topological constrains in the lamina, can be mitigated by tuning the properties of the chromatin interior. Thus, we find that the genome is a resistive mechanical element that can be tuned by its organization and connectivity to the lamina.

Gamma-tocopherol supplementation ameliorated hyper-inflammatory response during the early cutaneous wound healing in alloxan-induced diabetic mice

PubMed Central

Shin, Jihyun; Yang, Soo Jin

2016-01-01

Delayed wound healing is one of the major diabetic complications. During wound healing process, the early inflammatory stage is important for better prognosis. One of antioxidant nutrient, gamma-tocopherol (GT) is considered to regulate inflammatory conditions. This study investigated the effect of GT supplementation on mechanism associated with inflammation, oxidative stress, and apoptosis during early cutaneous wound healing in diabetic mice. Diabetes was induced by alloxan injection in ICR mice. All mice were divided into three groups: non-diabetic control mice (CON), diabetic control mice (DMC), and diabetic mice supplemented with GT (GT). After two weeks of GT supplementation, excisional wounds were made by biopsy punches (4 mm). Diabetic mice showed increases in fasting blood glucose (FBG) level, hyper-inflammatory response, oxidative stress, and delayed wound closure rate compared to non-diabetic mice. However, GT supplementation reduced FBG level and accelerated wound closure rate by regulation of inflammatory response-related proteins such as nuclear factor kappa B, interleukin-1β, tumor necrosis factor-α, and c-reactive protein, and oxidative stress-related markers including nuclear factor (erythroid derived 2)-like 2, NAD(P)H dehydrogenase quinone1, heme oxygenase-1, manganese superoxide dismutase, catalase and glutathione peroxidase and apoptosis-related markers such as sirtuin-1, peroxisome proliferator-activated receptor gamma coactivator 1-α, and p53 in diabetic mice. Taken together, GT would be a potential therapeutic to prevent diabetes-induced delayed wound healing by regulation of inflammatory response, apoptosis, and oxidative stress. Impact statement Gamma tocopherol has shown ameliorative effect on diabetic wound healing by regulation of inflammation, oxidative stress, and apoptosis demonstrated by nuclear factor kappa B, nuclear factor (erythroid derived 2)-like 2, and sirtuin-1. PMID:28211759

Gamma-tocopherol supplementation ameliorated hyper-inflammatory response during the early cutaneous wound healing in alloxan-induced diabetic mice.

PubMed

Shin, Jihyun; Yang, Soo Jin; Lim, Yunsook

2017-03-01

Delayed wound healing is one of the major diabetic complications. During wound healing process, the early inflammatory stage is important for better prognosis. One of antioxidant nutrient, gamma-tocopherol (GT) is considered to regulate inflammatory conditions. This study investigated the effect of GT supplementation on mechanism associated with inflammation, oxidative stress, and apoptosis during early cutaneous wound healing in diabetic mice. Diabetes was induced by alloxan injection in ICR mice. All mice were divided into three groups: non-diabetic control mice (CON), diabetic control mice (DMC), and diabetic mice supplemented with GT (GT). After two weeks of GT supplementation, excisional wounds were made by biopsy punches (4 mm). Diabetic mice showed increases in fasting blood glucose (FBG) level, hyper-inflammatory response, oxidative stress, and delayed wound closure rate compared to non-diabetic mice. However, GT supplementation reduced FBG level and accelerated wound closure rate by regulation of inflammatory response-related proteins such as nuclear factor kappa B, interleukin-1β, tumor necrosis factor-α, and c-reactive protein, and oxidative stress-related markers including nuclear factor (erythroid derived 2)-like 2, NAD(P)H dehydrogenase quinone1, heme oxygenase-1, manganese superoxide dismutase, catalase and glutathione peroxidase and apoptosis-related markers such as sirtuin-1, peroxisome proliferator-activated receptor gamma coactivator 1- α, and p53 in diabetic mice. Taken together, GT would be a potential therapeutic to prevent diabetes-induced delayed wound healing by regulation of inflammatory response, apoptosis, and oxidative stress. Impact statement Gamma tocopherol has shown ameliorative effect on diabetic wound healing by regulation of inflammation, oxidative stress, and apoptosis demonstrated by nuclear factor kappa B, nuclear factor (erythroid derived 2)-like 2, and sirtuin-1.

The influence of social environment in early life on the behavior, stress response, and reproductive system of adult male Norway rats selected for different attitudes to humans.

PubMed

Gulevich, R G; Shikhevich, S G; Konoshenko, M Yu; Kozhemyakina, R V; Herbeck, Yu E; Prasolova, L A; Oskina, I N; Plyusnina, I Z

2015-05-15

The influence of social disturbance in early life on behavior, response of blood corticosterone level to restraint stress, and endocrine and morphometric indices of the testes was studied in 2-month Norway rat males from three populations: not selected for behavior (unselected), selected for against aggression to humans (tame), and selected for increased aggression to humans (aggressive). The experimental social disturbance included early weaning, daily replacement of cagemates from days 19 to 25, and subsequent housing in twos till the age of 2months. The social disturbance increased the latent period of aggressive behavior in the social interaction test in unselected males and reduced relative testis weights in comparison to the corresponding control groups. In addition, experimental unselected rats had smaller diameters of seminiferous tubules and lower blood testosterone levels. In the experimental group, tame rats had lower basal corticosterone levels, and aggressive animals had lower hormone levels after restraint stress in comparison to the control. The results suggest that the selection in two directions for attitude to humans modifies the response of male rats to social disturbance in early life. In this regard, the selected rat populations may be viewed as a model for investigation of (1) neuroendocrinal mechanisms responsible for the manifestation of aggression and (2) interaction of the hypothalamic-pituitary-adrenal and hypothalamic-pituitary-gonadal systems in stress. Copyright © 2015 Elsevier Inc. All rights reserved.

Early-Life Persistent Vitamin D Deficiency Alters Cardiopulmonary Responses to Particulate Matter-Enhanced Atmospheric Smog in Adult Mice

EPA Science Inventory

This study demonstrates that early-life persistent vitamin D deficiency alters the cardiopulmonary response to smog in mice and may increase risk of adverse effects. Early life nutritional deficiencies can lead to increased cardiovascular susceptibility to environme...

[Nasal CPAP versus mechanical ventilation in 28 to 32-week preterm infants with early surfactant administration].

PubMed

Pérez, Luis Alfonso; González, Diana Marcela; Álvarez, Karen Margarita de Jesús; Díaz-Martínez, Luis Alfonso

2014-01-01

Continuous positive airway pressure (CPAP) is useful in low birth weight infants with respiratory distress, but it is not known if it is a better alternative to mechanical ventilation after early pulmonary surfactant administration. To compare the incidence of adverse events in 28 to 32-week newborns with respiratory distress managed with mechanical ventilation or CPAP after early surfactant administration. In total, 176 newborns were treated with CPAP and 147 with mechanical ventilation, all with Apgar scores >3 at five minutes and without apnea. The incidence of CPAP failure was 6.5% (95% CI: 11.3-22.8%); 29 patients died: 7 with CPAP (4.0%) and 22 with mechanical ventilation (15.0%, p<0.001). The relative risk of dying with CPAP versus mechanical ventilation was 0.27 (95% CI: 0.12-0.61), but after adjusting for confounding factors, CPAP use did not imply a higher risk of dying (RR=0.60; 95% CI: 0.29-1.24). Mechanical ventilation fatality rate was 5.70 (95% CI: 3.75-8.66) deaths/1,000 days-patient, while with CPAP it was 1.37 (95% CI: 0.65-2.88, p<0.001). Chronic lung disease incidence was lower with CPAP than with mechanical ventilation (RR=0.71; 95% CI: 0.54-0.96), as were intracranial hemorrhage (RR=0.28, 95% CI: 0.09-0.84) and sepsis (RR=0.67; 95%CI: 0.52-0.86), and it was similar for air leaks (RR=2.51; 95% CI: 0.83-7.61) and necrotizing enterocolitis (RR=1.68, 95% CI: 0.59-4.81). CPAP exposure of premature infants with respiratory distress syndrome is protective against chronic lung disease, intraventricular hemorrhage and sepsis compared to mechanical ventilation. No differences were observed regarding air leak syndrome or death.

Caregiver Responsiveness during Preschool Supports Cooperation in Kindergarten: Moderation by Children's Early Compliance

ERIC Educational Resources Information Center

Pratt, Megan E.; Lipscomb, Shannon T.; McClelland, Megan M.

2016-01-01

Research Findings: The current study examined how children's parent-reported compliance at age 3 (36 months) moderated the effects of 2 dimensions of directly observed early care and education (ECE) process quality (positivity/responsivity and cognitive stimulation) during the prekindergarten year (54 months) on teacher reports of children's…

First Steps to School Readiness: South Carolina's Response to At-Risk Early Childhood Population.

ERIC Educational Resources Information Center

Buford, Rhonda; Stegelin, Dolores A.

2003-01-01

Describes South Carolina's new state early childhood program, First Steps to School Readiness. Includes a profile of the state's at-risk child population, noting poverty and education risk indicators, and describing key program components. The article discusses program oversight, local program partnerships, program funding mechanisms, and local…

Nonlinear mechanical response of the extracellular matrix: learning from articular cartilage

NASA Astrophysics Data System (ADS)

Kearns, Sarah; Das, Moumita

2015-03-01

We study the mechanical structure-function relations in the extracellular matrix (ECM) with focus on nonlinear shear and compression response. As a model system, our study focuses on the ECM in articular cartilage tissue which has two major mechanobiological components: a network of the biopolymer collagen that acts as a stiff, reinforcing matrix, and a flexible aggrecan network that facilitates deformability. We model this system as a double network hydrogel made of interpenetrating networks of stiff and flexible biopolymers respectively. We study the linear and nonlinear mechanical response of the model ECM to shear and compression forces using a combination of rigidity percolation theory and energy minimization approaches. Our results may provide useful insights into the design principles of the ECM as well as biomimetic hydrogels that are mechanically robust and can, at the same time, easily adapt to cues in their surroundings.

Using variability to guide dimensional weighting: Associative mechanisms in early word learning

PubMed Central

Apfelbaum, Keith S.; McMurray, Bob

2013-01-01

At 14 months, children appear to struggle to apply their fairly well developed speech perception abilities to learning similar sounding words (e.g. bih/dih; Stager & Werker, 1997). However, variability in non-phonetic aspects of the training stimuli seems to aid word learning at this age. Extant theories of early word learning cannot account for this benefit of variability. We offer a simple explanation for this range of effects based on associative learning. Simulations suggest that if infants encode both non-contrastive information (e.g. cues to speaker voice) and meaningful linguistic cues (e.g. place of articulation or voicing), then associative learning mechanisms predict these variability effects in early word learning. Crucially, this means that despite the importance of task variables in predicting performance, this body of work shows that phonological categories are still developing in this age, and that the structure of non-informative cues has critical influences on word learning abilities. PMID:21609356

A zebrafish larval model reveals early tissue-specific innate immune responses to Mucor circinelloides.

PubMed

Voelz, Kerstin; Gratacap, Remi L; Wheeler, Robert T

2015-11-01

Mucormycosis is an emerging fungal infection that is clinically difficult to manage, with increasing incidence and extremely high mortality rates. Individuals with diabetes, suppressed immunity or traumatic injury are at increased risk of developing disease. These individuals often present with defects in phagocytic effector cell function. Research using mammalian models and phagocytic effector cell lines has attempted to decipher the importance of the innate immune system in host defence against mucormycosis. However, these model systems have not been satisfactory for direct analysis of the interaction between innate immune effector cells and infectious sporangiospores in vivo. Here, we report the first real-time in vivo analysis of the early innate immune response to mucormycete infection using a whole-animal zebrafish larval model system. We identified differential host susceptibility, dependent on the site of infection (hindbrain ventricle and swim bladder), as well as differential functions of the two major phagocyte effector cell types in response to viable and non-viable spores. Larval susceptibility to mucormycete spore infection was increased upon immunosuppressant treatment. We showed for the first time that macrophages and neutrophils were readily recruited in vivo to the site of infection in an intact host and that spore phagocytosis can be observed in real-time in vivo. While exploring innate immune effector recruitment dynamics, we discovered the formation of phagocyte clusters in response to fungal spores that potentially play a role in fungal spore dissemination. Spores failed to activate pro-inflammatory gene expression by 6 h post-infection in both infection models. After 24 h, induction of a pro-inflammatory response was observed only in hindbrain ventricle infections. Only a weak pro-inflammatory response was initiated after spore injection into the swim bladder during the same time frame. In the future, the zebrafish larva as a live whole

Overexpression of Forebrain CRH During Early Life Increases Trauma Susceptibility in Adulthood

PubMed Central

Toth, Mate; Flandreau, Elizabeth I; Deslauriers, Jessica; Geyer, Mark A; Mansuy, Isabelle M; Merlo Pich, Emilio; Risbrough, Victoria B

2016-01-01

Although early-life stress is a significant risk factor for developing anxiety disorders, including posttraumatic stress disorder (PTSD), the underlying mechanisms are unclear. Corticotropin releasing hormone (CRH) is disrupted in individuals with PTSD and early-life stress and hence may mediate the effects of early-life stress on PTSD risk. We hypothesized that CRH hyper-signaling in the forebrain during early development is sufficient to increase response to trauma in adulthood. To test this hypothesis, we induced transient, forebrain-specific, CRH overexpression during early-life (pre-puberty, CRHOEdev) in double-mutant mice (Camk2a-rtta2 × tetO-Crh) and tested their behavioral and gene expression responses to the predator stress model of PTSD in adulthood. In one cohort of CRHOEdev exposed and unexposed mice, avoidance and arousal behaviors were examined 7–15 days after exposure to predator stress. In another cohort, gene expression changes in Crhr1, Crhr2, and Fkbp51 in forebrain of CRHOEdev exposed and unexposed mice were examined 7 days after predator stress. CRHOEdev induced robust increases in startle reactivity and reductions in startle inhibition independently of predator stress in both male and female mice. Avoidance behaviors after predator stress were highly dependent on sex and CRHOEdev exposure. Whereas stressed females exhibited robust avoidance responses that were not altered by CRHOEdev, males developed significant avoidance only when exposed to both CRHOEdev and stress. Quantitative real-time-PCR analysis indicated that CRHOEdev unexposed males exhibit significant changes in Crhr2 expression in the amygdala and bed nucleus stria terminalis in response to stress, whereas males exposed to CRHOEdev did not. Similar to CRHOEdev males, females exhibited no significant Crhr2 gene expression changes in response to stress. Cortical Fkbp51 expression was also significantly reduced by stress and CRHOEdev exposure in males, but not in females. These

Elevated Peritoneal Fluid TNF-α Incites Ovarian Early Growth Response Factor 1 Expression and Downstream Protease Mediators

PubMed Central

Birt, Julie A.; Nabli, Henda; Stilley, Julie A.; Windham, Emma A.; Frazier, Shellaine R.

2013-01-01

Endometriosis-associated infertility manifests itself via multiple, poorly understood mechanisms. Our goal was to characterize signaling pathways, between peritoneal endometriotic lesions and the ovary, leading to failed ovulation. Genome-wide microarray analysis comparing ovarian tissue from an in vivo endometriosis model in the rat (Endo) with controls (Sham) identified 22 differentially expressed genes, including transiently expressed early growth response factor 1 (Egr1). The Egr1 regulates gene requisites for ovulation. The Egr1 promoter is responsive to tumor necrosis factor-alpha (TNF-α) signaling. We hypothesized that altered expression of ovarian EGR1 is induced by elevated peritoneal fluid TNF-α which is upregulated by the presence of peritoneal endometriosis. Endo rats, compared to controls, had more peritoneal fluid TNF-α and quantitative, spatial differences in Egr1 mRNA and EGR1 protein localization in follicular compartments. Interactions between elevated peritoneal fluid TNF-α and overexpression of follicular Egr1/EGR1 expression may affect downstream protease pathways impeding ovulation in endometriosis. Preliminary studies identified similar patterns of EGR1 protein localization in human ovaries from women with endometriosis and compared to those without endometriosis. PMID:23427178

High fidelity computational characterization of the mechanical response of thermally aged polycarbonate

NASA Astrophysics Data System (ADS)

Zhang, Zesheng; Zhang, Lili; Jasa, John; Li, Wenlong; Gazonas, George; Negahban, Mehrdad

2017-07-01

A representative all-atom molecular dynamics (MD) system of polycarbonate (PC) is built and conditioned to capture and predict the behaviours of PC in response to a broad range of thermo-mechanical loadings for various thermal aging. The PC system is constructed to have a distribution of molecular weights comparable to a widely used commercial PC (LEXAN 9034), and thermally conditioned to produce models for aged and unaged PC. The MD responses of these models are evaluated through comparisons to existing experimental results carried out at much lower loading rates, but done over a broad range of temperatures and loading modes. These experiments include monotonic extension/compression/shear, unilaterally and bilaterally confined compression, and load-reversal during shear. It is shown that the MD simulations show both qualitative and quantitative similarity with the experimental response. The quantitative similarity is evaluated by comparing the dilatational response under bilaterally confined compression, the shear flow viscosity and the equivalent yield stress. The consistency of the in silico response to real laboratory experiments strongly suggests that the current PC models are physically and mechanically relevant and potentially can be used to investigate thermo-mechanical response to loading conditions that would not easily be possible. These MD models may provide valuable insight into the molecular sources of certain observations, and could possibly offer new perspectives on how to develop constitutive models that are based on better understanding the response of PC under complex loadings. To this latter end, the models are used to predict the response of PC to complex loading modes that would normally be difficult to do or that include characteristics that would be difficult to measure. These include the responses of unaged and aged PC to unilaterally confined extension/compression, cyclic uniaxial/shear loadings, and saw-tooth extension/compression/shear.

Letrozole: a review of its use in the treatment of postmenopausal women with hormone-responsive early breast cancer.

PubMed

Keating, Gillian M

2009-08-20

Letrozole (Femara) is a third-generation, nonsteroidal aromatase inhibitor. Adjuvant therapy with letrozole is more effective than tamoxifen in postmenopausal women with hormone-responsive early breast cancer, and extended adjuvant therapy with letrozole after the completion of adjuvant tamoxifen therapy is more effective than placebo in this patient population; letrozole is generally well tolerated. Ongoing trials will help answer outstanding questions regarding the optimal duration of letrozole therapy in early breast cancer and its efficacy compared with other third-generation aromatase inhibitors such as anastrozole. In the meantime, letrozole should be considered a valuable option in the treatment of postmenopausal women with hormone-responsive early breast cancer, both as adjuvant and extended adjuvant therapy.

Early growth response-1 negative feedback regulates skeletal muscle postprandial insulin sensitivity via activating Ptp1b transcription.

PubMed

Wu, Jing; Tao, Wei-Wei; Chong, Dan-Yang; Lai, Shan-Shan; Wang, Chuang; Liu, Qi; Zhang, Tong-Yu; Xue, Bin; Li, Chao-Jun

2018-03-15

Postprandial insulin desensitization plays a critical role in maintaining whole-body glucose homeostasis by avoiding the excessive absorption of blood glucose; however, the detailed mechanisms that underlie how the major player, skeletal muscle, desensitizes insulin action remain to be elucidated. Herein, we report that early growth response gene-1 ( Egr-1) is activated by insulin in skeletal muscle and provides feedback inhibition that regulates insulin sensitivity after a meal. The inhibition of the transcriptional activity of Egr-1 enhanced the phosphorylation of the insulin receptor (InsR) and Akt, thus increasing glucose uptake in L6 myotubes after insulin stimulation, whereas overexpression of Egr-1 decreased insulin sensitivity. Furthermore, deletion of Egr-1 in the skeletal muscle improved systemic insulin sensitivity and glucose tolerance, which resulted in lower blood glucose levels after refeeding. Mechanistic analysis demonstrated that EGR-1 inhibited InsR phosphorylation and glucose uptake in skeletal muscle by binding to the proximal promoter region of protein tyrosine phosphatase-1B (PTP1B) and directly activating transcription. PTP1B knockdown largely restored insulin sensitivity and enhanced glucose uptake, even under conditions of EGR-1 overexpression. Our results indicate that EGR-1/PTP1B signaling negatively regulates postprandial insulin sensitivity and suggest a potential therapeutic target for the prevention and treatment of excessive glucose absorption.-Wu, J., Tao, W.-W., Chong, D.-Y., Lai, S.-S., Wang, C., Liu, Q., Zhang, T.-Y., Xue, B., Li, C.-J. Early growth response-1 negative feedback regulates skeletal muscle postprandial insulin sensitivity via activating Ptp1b transcription.

Early systemic bacterial dissemination and a rapid innate immune response characterize genetic resistance to plague of SEG mice.

PubMed

Demeure, Christian E; Blanchet, Charlène; Fitting, Catherine; Fayolle, Corinne; Khun, Huot; Szatanik, Marek; Milon, Geneviève; Panthier, Jean-Jacques; Jaubert, Jean; Montagutelli, Xavier; Huerre, Michel; Cavaillon, Jean-Marc; Carniel, Elisabeth

2012-01-01

Although laboratory mice are usually highly susceptible to Yersinia pestis, we recently identified a mouse strain (SEG) that exhibited an exceptional capacity to resist bubonic plague and used it to identify immune mechanisms associated with resistance. The kinetics of infection, circulating blood cells, granulopoiesis, lesions, and cellular populations in the spleen, and cytokine production in various tissues were compared in SEG and susceptible C57BL/6J mice after subcutaneous infection with the virulent Y. pestis CO92. Bacterial invasion occurred early (day 2) but was transient in SEG/Pas mice, whereas in C57BL/6J mice it was delayed but continuous until death. The bacterial load in all organs significantly correlated with the production of 5 cytokines (granulocyte colony-stimulating factor, keratinocyte-derived chemokine (KC), macrophage cationic peptide-1 (MCP-1), interleukin 1α, and interleukin 6) involved in monocyte and neutrophil recruitment. Indeed, higher proportions of these 2 cell types in blood and massive recruitment of F4/80(+)CD11b(-) macrophages in the spleen were observed in SEG/Pas mice at an early time point (day 2). Later times after infection (day 4) were characterized in C57BL/6J mice by destructive lesions of the spleen and impaired granulopoiesis. A fast and efficient Y. pestis dissemination in SEG mice may be critical for the triggering of an early and effective innate immune response necessary for surviving plague.

Developmental changes in automatic rule-learning mechanisms across early childhood.

PubMed

Mueller, Jutta L; Friederici, Angela D; Männel, Claudia

2018-06-27

Infants' ability to learn complex linguistic regularities from early on has been revealed by electrophysiological studies indicating that 3-month-olds, but not adults, can automatically detect non-adjacent dependencies between syllables. While different ERP responses in adults and infants suggest that both linguistic rule learning and its link to basic auditory processing undergo developmental changes, systematic investigations of the developmental trajectories are scarce. In the present study, we assessed 2- and 4-year-olds' ERP indicators of pitch discrimination and linguistic rule learning in a syllable-based oddball design. To test for the relation between auditory discrimination and rule learning, ERP responses to pitch changes were used as predictor for potential linguistic rule-learning effects. Results revealed that 2-year-olds, but not 4-year-olds, showed ERP markers of rule learning. Although, 2-year-olds' rule learning was not dependent on differences in pitch perception, 4-year-old children demonstrated a dependency, such that those children who showed more pronounced responses to pitch changes still showed an effect of rule learning. These results narrow down the developmental decline of the ability for automatic linguistic rule learning to the age between 2 and 4 years, and, moreover, point towards a strong modification of this change by auditory processes. At an age when the ability of automatic linguistic rule learning phases out, rule learning can still be observed in children with enhanced auditory responses. The observed interrelations are plausible causes for age-of-acquisition effects and inter-individual differences in language learning. © 2018 John Wiley & Sons Ltd.

Insights into Metabolic Mechanisms Underlying Folate-Responsive Neural Tube Defects: A Minireview

PubMed Central

Beaudin, Anna E.; Stover, Patrick J.

2015-01-01

Neural tube defects (NTDs), including anencephaly and spina bifida, arise from the failure of neurulation during early embryonic development. Neural tube defects are common birth defects with a heterogenous and multifactorial etiology with interacting genetic and environmental risk factors. Although the mechanisms resulting in failure of neural tube closure are unknown, up to 70% of NTDs can be prevented by maternal folic acid supplementation. However, the metabolic mechanisms underlying the association between folic acid and NTD pathogenesis have not been identified. This review summarizes our current understanding of the mechanisms by which impairments in folate metabolism might ultimately lead to failure of neural tube closure, with an emphasis on untangling the relative contributions of nutritional deficiency and genetic risk factors to NTD pathogenesis. PMID:19180567

Role of phase instabilities in the early response of bulk fused silica during laser-induced breakdown

NASA Astrophysics Data System (ADS)

Demange, P.; Negres, R. A.; Raman, R. N.; Colvin, J. D.; Demos, S. G.

2011-08-01

We report on the experimental and hydrocode modeling investigation of the early material response to localized energy deposition via nanosecond laser pulses in bulk fused silica. A time-resolved microscope system was used to acquire transient images with adequate spatial and temporal resolution to resolve the material behavior from the onset of the process. These images revealed a high-pressure shock front propagating at twice the speed of sound at ambient conditions and bounding a region of modified material at delays up to one nanosecond. Hydrocode simulations matching the experimental conditions were also performed and indicated initial pressures of ˜40 GPa and temperatures of ˜1 eV at the absorption region. Both the simulations and the image data show a clear boundary between distinct material phases, a hot plasma and solid silica, with a suggestion that growth of perturbations at the Rayleigh-Taylor unstable interface between the two phases is the seed mechanism for the growth of cracks into the stressed solid.

Early response to venlafaxine antidepressant correlates with lower ACTH levels prior to pharmacological treatment.

PubMed

Araya, A V; Rojas, P; Fritsch, R; Rojas, R; Herrera, L; Rojas, G; Gatica, H; Silva, H; Fiedler, J L

2006-12-01

A link between stressful life events and development or exacerbation of depression has been established via a large body of evidence. An alteration in the regulation of the hypothalamic-pituitary-adrenal (HPA) axis in depression has also been associated with an increase in cortisol secretion. As arginine-vasopressin (AVP) plays an important role in the activation of HPA axis during stress, the present study investigated ACTH and cortisol secretory response induced by an AVP-related peptide desmopressin (ddAVP) in patients with major depression. Prior to antidepressant treatment, endocrinological parameters were evaluated and correlated with the clinical response to venlafaxine treatment, which offers a dual antidepressant action. Depressive patients with no other psychiatric pathology were evaluated with 17-item Hamilton Depression Scale (HAM-D) in order to follow-up the response to venlafaxine. After 1 wk of treatment, 60% of patients reduced their initial HAM-D score to at least 25%; this group was classified as early responders. The other group (40%) started to reduce significantly their HAM-D score after 3 wk of treatment and was classified as late responders. After 6 wk of treatment both groups have reduced HAM-D score to at least 25% of the baseline score. Prior to the pharmacological treatment, both early and late responders showed salivary cortisol rhythm and urinary free cortisol (UFC) in 24-h similar to healthy subjects. However, we did observe differences in basal ACTH secretion, showing that the late responder group had higher basal ACTH than both early responders and controls. The ddAVP challenge promoted a robust secretion of ACTH only in late responders, suggesting a different sensitivity of pituitary vasopressin receptor. The differences in clinical response to venlafaxine among depressive patients seem to be related to endocrinological parameters.

Expression of Putative Immune Response Genes during Early Ontogeny in the Coral Acropora millepora

PubMed Central

Puill-Stephan, Eneour; Seneca, François O.; Miller, David J.; van Oppen, Madeleine J. H.; Willis, Bette L.

2012-01-01

Background Corals, like many other marine invertebrates, lack a mature allorecognition system in early life history stages. Indeed, in early ontogeny, when corals acquire and establish associations with various surface microbiota and dinoflagellate endosymbionts, they do not efficiently distinguish between closely and distantly related individuals from the same population. However, very little is known about the molecular components that underpin allorecognition and immunity responses or how they change through early ontogeny in corals. Methodology/Principal Findings Patterns in the expression of four putative immune response genes (apextrin, complement C3, and two CELIII type lectin genes) were examined in juvenile colonies of Acropora millepora throughout a six-month post-settlement period using quantitative real-time PCR (qPCR). Expression of a CELIII type lectin gene peaked in the fourth month for most of the coral juveniles sampled and was significantly higher at this time than at any other sampling time during the six months following settlement. The timing of this increase in expression levels of putative immune response genes may be linked to allorecognition maturation which occurs around this time in A.millepora. Alternatively, the increase may represent a response to immune challenges, such as would be involved in the recognition of symbionts (such as Symbiodinium spp. or bacteria) during winnowing processes as symbioses are fine-tuned. Conclusions/Significance Our data, although preliminary, are consistent with the hypothesis that lectins may play an important role in the maturation of allorecognition responses in corals. The co-expression of lectins with apextrin during development of coral juveniles also raises the possibility that these proteins, which are components of innate immunity in other invertebrates, may influence the innate immune systems of corals through a common pathway or system. However, further studies investigating the expression of

Parathyroid hormone modulates the response of osteoblast-like cells to mechanical stimulation

NASA Technical Reports Server (NTRS)

Ryder, K. D.; Duncan, R. L.

2000-01-01

Mechanical loading stimulates many responses in bone and osteoblasts associated with osteogenesis. Since loading and parathyroid hormone (PTH) activate similar signaling pathways in osteoblasts, we postulate that PTH can potentiate the effects of mechanical stimulation. Using an in vitro four-point bending device, we found that expression of COX-2, the inducible isoform of cyclooxygenase, was dependent on fluid forces generated across the culture plate, but not physiologic levels of strain in MC3T3-E1 osteoblast-like cells. Addition of 50 nM PTH during loading increased COX-2 expression at both subthreshold and threshold levels of fluid forces compared with either stimuli alone. We also demonstrated that application of fluid shear to MC3T3-E1 cells induced a rapid increase in [Ca(2+)](i). Although PTH did not significantly change [Ca(2+)](i) levels, flow and PTH did produce a significantly greater [Ca(2+)](i) response and increased the number of responding cells than is found in fluid shear alone. The [Ca(2+)](i) response to these stimuli was significantly decreased when the mechanosensitive channel inhibitor, gadolinium, was present. These studies indicate that PTH increases the cellular responses of osteoblasts to mechanical loading. Furthermore, this response may be mediated by alterations in [Ca(2+)](i) by modulating the mechanosensitive channel.

Early loss of the glucagon response to hypoglycemia in adolescents with type 1 diabetes.

PubMed

Siafarikas, Aris; Johnston, Robert J; Bulsara, Max K; O'Leary, Peter; Jones, Timothy W; Davis, Elizabeth A

2012-08-01

To assess the glucagon response to hypoglycemia and identify influencing factors in patients with type 1 diabetes compared with nondiabetic control subjects. Hyperinsulinemic hypoglycemic clamp studies were performed in all participants. The glucagon response to both hypoglycemia and arginine was measured, as well as epinephrine, cortisol, and growth hormone responses to hypoglycemia. Residual β-cell function was assessed using fasting and stimulated C-peptide. Twenty-eight nonobese adolescents with type 1 diabetes (14 female, mean age 14.9 years [range 11.2-19.8]) and 12 healthy control subjects (6 female, 15.3 years [12.8-18.7]) participated in the study. Median duration of type 1 diabetes was 0.66 years (range 0.01-9.9). The glucagon peak to arginine stimulation was similar between groups (P = 0.27). In contrast, the glucagon peak to hypoglycemia was reduced in the group with diabetes (95% CI): 68 (62-74) vs. 96 (87-115) pg/mL (P < 0.001). This response was greater than 3 SDs from baseline for only 7% of subjects with type 1 diabetes in comparison with 83% of control subjects and was lost at a median duration of diabetes of 8 months and as early as 1 month after diagnosis (R = -0.41, P < 0.01). There was no correlation in response with height, weight, BMI, and HbA(1c). Epinephrine, cortisol, and growth hormone responses to hypoglycemia were present in both groups. The glucagon response to hypoglycemia in adolescents with type 1 diabetes is influenced by the duration of diabetes and can be lost early in the course of the disease.

Transcriptome Analysis of Early Responsive Genes in Rice during Magnaporthe oryzae Infection.

PubMed

Wang, Yiming; Kwon, Soon Jae; Wu, Jingni; Choi, Jaeyoung; Lee, Yong-Hwan; Agrawal, Ganesh Kumar; Tamogami, Shigeru; Rakwal, Randeep; Park, Sang-Ryeol; Kim, Beom-Gi; Jung, Ki-Hong; Kang, Kyu Young; Kim, Sang Gon; Kim, Sun Tae

2014-12-01

Rice blast disease caused by Magnaporthe oryzae is one of the most serious diseases of cultivated rice (Oryza sativa L.) in most rice-growing regions of the world. In order to investigate early response genes in rice, we utilized the transcriptome analysis approach using a 300 K tilling microarray to rice leaves infected with compatible and incompatible M. oryzae strains. Prior to the microarray experiment, total RNA was validated by measuring the differential expression of rice defense-related marker genes (chitinase 2, barwin, PBZ1, and PR-10) by RT-PCR, and phytoalexins (sakuranetin and momilactone A) with HPLC. Microarray analysis revealed that 231 genes were up-regulated (>2 fold change, p < 0.05) in the incompatible interaction compared to the compatible one. Highly expressed genes were functionally characterized into metabolic processes and oxidation-reduction categories. The oxidative stress response was induced in both early and later infection stages. Biotic stress overview from MapMan analysis revealed that the phytohormone ethylene as well as signaling molecules jasmonic acid and salicylic acid is important for defense gene regulation. WRKY and Myb transcription factors were also involved in signal transduction processes. Additionally, receptor-like kinases were more likely associated with the defense response, and their expression patterns were validated by RT-PCR. Our results suggest that candidate genes, including receptor-like protein kinases, may play a key role in disease resistance against M. oryzae attack.

Exploring Higher Education's Response to the Early Childhood Education Teacher Shortage

ERIC Educational Resources Information Center

Matczak, Melissa L.

2017-01-01

This qualitative single case study attempt is to explore how one institution of higher education can be responsive in meeting the needs of a teacher shortage in early childhood education and the factors impacting (hindering and helping) the collaborative partner process of designing an Applied Bachelor's in Science Degree in Elementary Education…

Early Detection Rapid Response Program Targets New Noxious Weed Species in Washington State

ERIC Educational Resources Information Center

Andreas, Jennifer E.; Halpern, Alison D.; DesCamp, Wendy C.; Miller, Timothy W.

2015-01-01

Early detection, rapid response is a critical component of invasive plant management. It can be challenging, however, to detect new invaders before they become established if landowners cannot identify species of concern. In order to increase awareness, eye-catching postcards were developed in Washington State as part of a noxious weed educational…

Mechanotransduction and the functional response of bone to mechanical strain

NASA Technical Reports Server (NTRS)

Duncan, R. L.; Turner, C. H.

1995-01-01

Mechanotransduction plays a crucial role in the physiology of many tissues including bone. Mechanical loading can inhibit bone resorption and increase bone formation in vivo. In bone, the process of mechanotransduction can be divided into four distinct steps: (1) mechanocoupling, (2) biochemical coupling, (3) transmission of signal, and (4) effector cell response. In mechanocoupling, mechanical loads in vivo cause deformations in bone that stretch bone cells within and lining the bone matrix and create fluid movement within the canaliculae of bone. Dynamic loading, which is associated with extracellular fluid flow and the creation of streaming potentials within bone, is most effective for stimulating new bone formation in vivo. Bone cells in vitro are stimulated to produce second messengers when exposed to fluid flow or mechanical stretch. In biochemical coupling, the possible mechanisms for the coupling of cell-level mechanical signals into intracellular biochemical signals include force transduction through the integrin-cytoskeleton-nuclear matrix structure, stretch-activated cation channels within the cell membrane, G protein-dependent pathways, and linkage between the cytoskeleton and the phospholipase C or phospholipase A pathways. The tight interaction of each of these pathways would suggest that the entire cell is a mechanosensor and there are many different pathways available for the transduction of a mechanical signal. In the transmission of signal, osteoblasts, osteocytes, and bone lining cells may act as sensors of mechanical signals and may communicate the signal through cell processes connected by gap junctions. These cells also produce paracrine factors that may signal osteoprogenitors to differentiate into osteoblasts and attach to the bone surface. Insulin-like growth factors and prostaglandins are possible candidates for intermediaries in signal transduction. In the effector cell response, the effects of mechanical loading are dependent upon the

Response to Early AED Therapy and Its Prognostic Implications

PubMed Central

French, Jacqueline A.

2002-01-01

Determining the prognosis of patients when they first present with epilepsy is a difficult task. Several clinical studies have shed light on this very important topic. Potential predictors of the refractory state, including seizure etiology, duration of epilepsy before treatment, and epilepsy type, have not been successful indicators of long-term outcome. One predictor of the refractory state appears to be early response to AED therapy. Inadequate seizure control after initial treatment is a poor prognostic sign. Recent research into genetic causes of the refractory state has included investigation of the multiple drug resistance gene, and polymorphisms at drug targets. More work is needed to determine the causes and predictors of drug resistance. PMID:15309146

Stress Response Mechanisms: From Single Cells to Multinational Organizations

PubMed Central

Pech, Richard J.

2006-01-01

Can a literal comparison be made between biological phenomena in organisms and phenomena in human organizations? The evidence provided by simplified but useful examples appears to suggest that a phenomenon simulating hormesis can and does occur in organizational contexts. Similarities between stress response behaviors of organisms and stress response behaviors in organizations are discussed. Cellular stress response mechanisms stimulate and repair, as well as defend the organism against further attacks. Organizational hormesis describes actions that stimulate the organization by increasing its focus and protecting it against future attacks. The common aim for the organism as well as the organization is to increase the probability of survival. The following describes examples of organizational survival that demonstrate a number of hormetic parallels between organisms and organisations. PMID:18648597

A gene expression profile indicative of early stage HER2 targeted therapy response.

PubMed

O'Neill, Fiona; Madden, Stephen F; Clynes, Martin; Crown, John; Doolan, Padraig; Aherne, Sinéad T; O'Connor, Robert

2013-07-01

Efficacious application of HER2-targetting agents requires the identification of novel predictive biomarkers. Lapatinib, afatinib and neratinib are tyrosine kinase inhibitors (TKIs) of HER2 and EGFR growth factor receptors. A panel of breast cancer cell lines was treated with these agents, trastuzumab, gefitinib and cytotoxic therapies and the expression pattern of a specific panel of genes using RT-PCR was investigated as a potential marker of early drug response to HER2-targeting therapies. Treatment of HER2 TKI-sensitive SKBR3 and BT474 cell lines with lapatinib, afatinib and neratinib induced an increase in the expression of RB1CC1, ERBB3, FOXO3a and NR3C1. The response directly correlated with the degree of sensitivity. This expression pattern switched from up-regulated to down-regulated in the HER2 expressing, HER2-TKI insensitive cell line MDAMB453. Expression of the CCND1 gene demonstrated an inversely proportional response to drug exposure. A similar expression pattern was observed following the treatment with both neratinib and afatinib. These patterns were retained following exposure to traztuzumab and lapatinib plus capecitabine. In contrast, gefitinib, dasatinib and epirubicin treatment resulted in a completely different expression pattern change. In these HER2-expressing cell line models, lapatinib, neratinib, afatinib and trastuzumab treatment generated a characteristic and specific gene expression response, proportionate to the sensitivity of the cell lines to the HER2 inhibitor.Characterisation of the induced changes in expression levels of these genes may therefore give a valuable, very early predictor of the likely extent and specificity of tumour HER2 inhibitor response in patients, potentially guiding more specific use of these agents.

Experimental investigation on local mechanical response of superelastic NiTi shape memory alloy

NASA Astrophysics Data System (ADS)

Xiao, Yao; Zeng, Pan; Lei, Liping

2016-01-01

In this paper, primary attention is paid to the local mechanical response of NiTi shape memory alloy (SMA) under uniaxial tension. With the help of in situ digital image correlation, sets of experiments are conducted to measure the local strain field at various thermomechanical conditions. Two types of mechanical responses of NiTi SMA are identified. The residual strain localization phenomena are observed, which can be attributed to the localized phase transformation (PT) and we affirm that most of the irreversibility is accumulated simultaneously during PT. It is found that temperature and PT play important roles in inducing delocalization of the reverse transformation. We conclude that forward transformation has more influence on the transition of mechanical response in NiTi SMA than reverse transformation in terms of the critical transition temperature for inducing delocalized reverse transformation.

The mechanical response of woven Kevlar fabric

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

Warren, W.E.

1991-01-01

Woven Kevlar fabrics exhibit a number of beneficial mechanical properties which include strength, flexibility, and relatively low density. The desire to engineer or design Kevlar fabrics for specific applications has stimulated interest in the development of theoretical models which relate their effective mechanical properties to specific aspects of the fabric morphology and microstructure. In this work the author provides a theoretical investigation of the large deformation elastic response of a plane woven Kevlar fabric and compares these theoretical results with experimental data obtained from uniaxially loaded Kevlar fabrics. The theoretical analysis assumes the woven fabric to be a regular networkmore » of orthogonal interlaced yarns and the individual yarns are modeled as extensible elastica, thus coupling stretching and bending effects at the outset. This comparison of experiment with theory indicates that the deformation of woven fabric can be quite accurately predicted by modeling the individual yarns as extensible elastica. 2 refs., 1 fig.« less

Cytomegalovirus: pathophysiological mechanisms of the cytomegalovirus-induced cellular responses

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

Nokta, M.A.

1986-01-01

Cytomegalovirus (CMV) infection of fibroblasts of human origin is associated with a cascade of morphologic cellular responses which in other systems have been associated with regulation of intracellular free (IF) (Ca/sup + +/). In the present study, the relationship of specific ion fluxes (Ca/sup + +/, Na/sup +/) to the development of cytomegalovirus (CMV)-induced morphologic cellular responses was investigated. An influx of Ca/sup + +/ was observed by the first hour after CMV infection (PI), and total calcium sequestered by infected cells was enhanced by 5 hr Pl. A gradual rise in intracellular free (IF) (Ca/sup + +/) was observedmore » that continued through 48 hour postinfection (hr Pl). The IF (Ca/sup + +/) response to CMV infection was shown to be multiplicity dependent, require viable virus, and occur under conditions consistent with the expression of immediate early CMV genes. Development and progression of cytomegaly was found to be independent of CMV DNA synthesis and appeared to be dependent on the IF (Ca/sup + +/) response. Ca/sup + +/ influx blockers (e.g. verapamil) and cyclic nucleotide modulators (e.g. papaverine) inhibited both Ca/sup + +/ responses and cytomegaly. Quabain-sensitive /sup 86/Rb uptake and sequestering of Ca/sup + +/ increased in parallel with development of cytomegaly. There may be a relationship between Ca/sup + +/ influx, IF (Ca/sup + +/), activation of the Na/sup +//H/sup +/ exchanger, induction of Na/sup +/, Cl/sup -/, HCO/sub 3/ cotransport, Na/sup +/ entry, Na/sup +//K/sup +/ ATPase activity and development of CMV-induced morphologic cellular responses including cytomegaly.« less

Integrin αv in the mechanical response of osteoblast lineage cells.

PubMed

Kaneko, Keiko; Ito, Masako; Naoe, Yoshinori; Lacy-Hulbert, Adam; Ikeda, Kyoji

2014-05-02

Although osteoblast lineage cells, especially osteocytes, are thought to be a primary mechanosensory cell in bone, the identity of the mechano-receptor and downstream mechano-signaling pathways remain largely unknown. Here we show using osteoblastic cell model of mechanical stimulation with fluid shear stress that in the absence of integrin αv, phosphorylation of the Src substrate p130Cas and JNK was impaired, culminating in an inhibition of nuclear translocation of YAP/TAZ and subsequent transcriptional activation of target genes. Targeted deletion of the integrin αv in osteoblast lineage cells results in an attenuated response to mechanical loading in terms of Sost gene expression, indicative of a role for integrin αv in mechanoreception in vivo. Thus, integrin αv may be integral to a mechanosensing machinery in osteoblastic cells and involved in activation of a Src-JNK-YAP/TAZ pathway in response to mechanical stimulation. Copyright © 2014 Elsevier Inc. All rights reserved.

Understanding the Mechanisms Through Which an Influential Early Childhood Program Boosted Adult Outcomes

PubMed Central

Heckman, James; Pinto, Rodrigo

2013-01-01

A growing literature establishes that high quality early childhood interventions targeted toward disadvantaged children have substantial impacts on later life outcomes. Little is known about the mechanisms producing these impacts. This paper uses longitudinal data on cognitive and personality traits from an experimental evaluation of the influential Perry Preschool program to analyze the channels through which the program boosted both male and female participant outcomes. Experimentally induced changes in personality traits explain a sizable portion of adult treatment effects. PMID:24634518

Eye coding mechanisms in early human face event-related potentials.

PubMed

Rousselet, Guillaume A; Ince, Robin A A; van Rijsbergen, Nicola J; Schyns, Philippe G

2014-11-10

In humans, the N170 event-related potential (ERP) is an integrated measure of cortical activity that varies in amplitude and latency across trials. Researchers often conjecture that N170 variations reflect cortical mechanisms of stimulus coding for recognition. Here, to settle the conjecture and understand cortical information processing mechanisms, we unraveled the coding function of N170 latency and amplitude variations in possibly the simplest socially important natural visual task: face detection. On each experimental trial, 16 observers saw face and noise pictures sparsely sampled with small Gaussian apertures. Reverse-correlation methods coupled with information theory revealed that the presence of the eye specifically covaries with behavioral and neural measurements: the left eye strongly modulates reaction times and lateral electrodes represent mainly the presence of the contralateral eye during the rising part of the N170, with maximum sensitivity before the N170 peak. Furthermore, single-trial N170 latencies code more about the presence of the contralateral eye than N170 amplitudes and early latencies are associated with faster reaction times. The absence of these effects in control images that did not contain a face refutes alternative accounts based on retinal biases or allocation of attention to the eye location on the face. We conclude that the rising part of the N170, roughly 120-170 ms post-stimulus, is a critical time-window in human face processing mechanisms, reflecting predominantly, in a face detection task, the encoding of a single feature: the contralateral eye. © 2014 ARVO.

Molecular response of canola to salt stress: insights on tolerance mechanisms.

PubMed

Shokri-Gharelo, Reza; Noparvar, Pouya Motie

2018-01-01

Canola ( Brassica napus L. ) is widely cultivated around the world for the production of edible oils and biodiesel fuel. Despite many canola varieties being described as 'salt-tolerant', plant yield and growth decline drastically with increasing salinity. Although many studies have resulted in better understanding of the many important salt-response mechanisms that control salt signaling in plants, detoxification of ions, and synthesis of protective metabolites, the engineering of salt-tolerant crops has only progressed slowly. Genetic engineering has been considered as an efficient method for improving the salt tolerance of canola but there are many unknown or little-known aspects regarding canola response to salinity stress at the cellular and molecular level. In order to develop highly salt-tolerant canola, it is essential to improve knowledge of the salt-tolerance mechanisms, especially the key components of the plant salt-response network. In this review, we focus on studies of the molecular response of canola to salinity to unravel the different pieces of the salt response puzzle. The paper includes a comprehensive review of the latest studies, particularly of proteomic and transcriptomic analysis, including the most recently identified canola tolerance components under salt stress, and suggests what researchers should focus on in future studies.

'Omics' techniques for identifying flooding-response mechanisms in soybean.

PubMed

Komatsu, Setsuko; Shirasaka, Naoki; Sakata, Katsumi

2013-11-20

Plant growth and productivity are adversely influenced by various environmental stresses, which often lead to reduced seedling growth and decreased crop yields. Plants respond to stressful conditions through changes in 'omics' profiles, including transcriptomics, proteomics, and metabolomics. Linking plant phenotype to gene expression patterns, protein abundance, and metabolite accumulation is one of the main challenges for improving agricultural production. 'Omics' approaches may shed insight into the mechanisms that function in soybean in response to environmental stresses, particularly flooding by frequent rain, which occurs worldwide due to changes in global climate. Flooding causes significant reductions in the growth and yield of several crops, especially soybean. The application of 'omics' techniques may facilitate the development of flood-tolerant cultivars of soybean. In this review, the use of 'omics' techniques towards understanding the flooding-responsive mechanisms of soybeans is discussed, as the findings from these studies are expected to have applications in both breeding and agronomy. This article is part of a Special Issue entitled: Translational Plant Proteomics. Copyright © 2012 Elsevier B.V. All rights reserved.

Vitamin A supplementation in early life affects later response to an obesogenic diet in rats.

PubMed

Granados, N; Amengual, J; Ribot, J; Musinovic, H; Ceresi, E; von Lintig, J; Palou, A; Bonet, M L

2013-09-01

To assess the influence of supplementation with a moderate dose of vitamin A in early life on adipose tissue development and the response to an obesogenic diet later in life. During the suckling period, rat pups received a daily oral dose of retinyl palmitate corresponding to three times the vitamin A ingested daily from maternal milk. Control rats received the vehicle (olive oil). Short-term effects of treatment on gene expression and morphology of white adipose tissue (WAT) were analyzed in animals on the day after weaning (day 21). To study long-term effects, control and vitamin A-treated rats were fed, after weaning, a normal fat or a high-fat (HF) diet for 16 weeks. WAT of vitamin A-treated young rats (day 21) was enriched in small adipocytes with a reduced expression of adipogenic markers (peroxisome proliferator-activated receptor γ and lipoprotein lipase) and an increased cell proliferation potential as indicated by increased expression of proliferating cell nuclear antigen. Increased retinoic acid (RA)-induced transcriptional responses were present in the tissues of vitamin A-treated young rats (day 21) including WAT. Vitamin A-treated rats developed higher adiposity than control rats on a HF diet as indicated by body composition analysis and increased WAT depot mass, adipocyte diameter, WAT DNA content, leptinemia and adipose leptin gene expression. Excess adiposity gain in vitamin A-treated rats developed in the absence of changes in body weight and was attributable to excess adipocyte hyperplasia. No differences in adiposity were observed between vitamin A-treated rats and control rats on a normal fat diet. Total retinol levels in WAT of vitamin A-treated rats were elevated at weaning (day 21) and normalized by day 135 of age. Vitamin A intake in the early stages of postnatal life favors subsequent HF diet-induced adiposity gain through mechanisms that may relate to changes in adipose tissue development, likely mediated by RA.

Sensory Temporal Processing in Adults with Early Hearing Loss

ERIC Educational Resources Information Center

Heming, Joanne E.; Brown, Lenora N.

2005-01-01

This study examined tactile and visual temporal processing in adults with early loss of hearing. The tactile task consisted of punctate stimulations that were delivered to one or both hands by a mechanical tactile stimulator. Pairs of light emitting diodes were presented on a display for visual stimulation. Responses consisted of YES or NO…

Mechanism of repression of the inhibin alpha-subunit gene by inducible 3',5'-cyclic adenosine monophosphate early repressor.

PubMed

Burkart, Anna D; Mukherjee, Abir; Mayo, Kelly E

2006-03-01

The rodent ovary is regulated throughout the reproductive cycle to maintain normal cyclicity. Ovarian follicular development is controlled by changes in gene expression in response to the gonadotropins FSH and LH. The inhibin alpha-subunit gene belongs to a group of genes that is positively regulated by FSH and negatively regulated by LH. Previous studies established an important role for inducible cAMP early repressor (ICER) in repression of alpha-inhibin. These current studies investigate the mechanisms of repression by ICER. It is not clear whether all four ICER isoforms expressed in the ovary can act as repressors of the inhibin alpha-subunit gene. EMSAs demonstrate binding of all isoforms to the inhibin alpha-subunit CRE (cAMP response element), and transfection studies demonstrate that all isoforms can repress the inhibin alpha-subunit gene. Repression by ICER is dependent on its binding to DNA as demonstrated by mutations to ICER's DNA-binding domain. These mutational studies also demonstrate that repression by ICER is not dependent on heterodimerization with CREB (CRE-binding protein). Competitive EMSAs show that ICER effectively competes with CREB for binding to the inhibin alpha CRE in vitro. Chromatin immunoprecipitation assays demonstrate a replacement of CREB dimers bound to the inhibin alpha CRE by ICER dimers in ovarian granulosa cells in response to LH signaling. Thus, there is a temporal association of transcription factors bound to the inhibin alpha-CRE controlling inhibin alpha-subunit gene expression.

Amount of fear extinction changes its underlying mechanisms

PubMed Central

An, Bobae; Kim, Jihye; Park, Kyungjoon; Lee, Sukwon; Song, Sukwoon; Choi, Sukwoo

2017-01-01

There has been a longstanding debate on whether original fear memory is inhibited or erased after extinction. One possibility that reconciles this uncertainty is that the inhibition and erasure mechanisms are engaged in different phases (early or late) of extinction. In this study, using single-session extinction training and its repetition (multiple-session extinction training), we investigated the inhibition and erasure mechanisms in the prefrontal cortex and amygdala of rats, where neural circuits underlying extinction reside. The inhibition mechanism was prevalent with single-session extinction training but faded when single-session extinction training was repeated. In contrast, the erasure mechanism became prevalent when single-session extinction training was repeated. Moreover, ablating the intercalated neurons of amygdala, which are responsible for maintaining extinction-induced inhibition, was no longer effective in multiple-session extinction training. We propose that the inhibition mechanism operates primarily in the early phase of extinction training, and the erasure mechanism takes over after that. DOI: http://dx.doi.org/10.7554/eLife.25224.001 PMID:28671550

Immune response profiling in early rheumatoid arthritis: discovery of a novel interaction of treatment response with viral immunity

PubMed Central

2013-01-01

Introduction It remains challenging to predict the outcomes of therapy in patients with rheumatoid arthritis (RA). The objective of this study was to identify immune response signatures that correlate with clinical treatment outcomes in patients with RA. Methods A cohort of 71 consecutive patients with early RA starting treatment with disease-modifying antirheumatic drugs (DMARDs) was recruited. Disease activity at baseline and after 21 to 24 weeks of follow-up was measured using the Disease Activity Score in 28 joints (DAS28). Immune response profiling was performed by analyzing multi-cytokine production from peripheral blood cells following incubation with a panel of stimuli, including a mixture of human cytomegalovirus (CMV) and Epstein-Barr virus (EBV) lysates. Profiles identified via principal components analysis (PCA) for each stimulus were then correlated with the ΔDAS28 from baseline to follow-up. A clinically meaningful improvement in the DAS28 was defined as a decrease of ≥1.2. Results A profile of T-cell cytokines (IL-13, IL-4, IL-5, IL-2, IL-12, and IFN-γ) produced in response to CMV/EBV was found to correlate with the ΔDAS28 from baseline to follow-up. At baseline, a higher magnitude of the CMV/EBV immune response profile predicted inadequate DAS28 improvement (mean PCA-1 scores: 65.6 versus 50.2; P = 0.029). The baseline CMV/EBV response was particularly driven by IFN-γ (P = 0.039) and IL-4 (P = 0.027). Among patients who attained clinically meaningful DAS28 improvement, the CMV/EBV PCA-1 score increased from baseline to follow-up (mean +11.6, SD 25.5), whereas among patients who responded inadequately to DMARD therapy, the CMV/EBV PCA-1 score decreased (mean -12.8, SD 25.4; P = 0.002). Irrespective of the ΔDAS28, methotrexate use was associated with up-regulation of the CMV/EBV response. The CMV/EBV profile was associated with positive CMV IgG (P <0.001), but not EBV IgG (P = 0.32), suggesting this response was related to

Early Blood-Brain Barrier Disruption after Mechanical Thrombectomy in Acute Ischemic Stroke.

PubMed

Shi, Zhong-Song; Duckwiler, Gary R; Jahan, Reza; Tateshima, Satoshi; Szeder, Viktor; Saver, Jeffrey L; Kim, Doojin; Sharma, Latisha K; Vespa, Paul M; Salamon, Noriko; Villablanca, J Pablo; Viñuela, Fernando; Feng, Lei; Loh, Yince; Liebeskind, David S

2018-05-01

The impact of blood-brain barrier (BBB) disruption can be detected by intraparenchymal hyperdense lesion on the computed tomography (CT) scan after endovascular stroke therapy. The purpose of this study was to determine whether early BBB disruption predicts intracranial hemorrhage and poor outcome in patients with acute ischemic stroke treated with mechanical thrombectomy. We analyzed patients with anterior circulation stroke treated with mechanical thrombectomy and identified BBB disruption on the noncontrast CT images immediately after endovascular treatment. Follow-up CT or magnetic resonance imaging scan was performed at 24 hours to assess intracranial hemorrhage. We dichotomized patients into those with moderate BBB disruption versus those with minor BBB disruption and no BBB disruption. We evaluated the association of moderate BBB disruption after mechanical thrombectomy with intracranial hemorrhage and clinical outcomes. Moderate BBB disruption after mechanical thrombectomy was found in 56 of 210 patients (26.7%). Moderate BBB disruption was independently associated with higher rates of hemorrhagic transformation (OR 25.33; 95% CI 9.93-64.65; P < .001), parenchymal hematoma (OR 20.57; 95% CI 5.64-74.99; P < .001), and poor outcome at discharge (OR 2.35; 95% CI 1.09-5.07; P = .03). The association of BBB disruption with intracranial hemorrhage remained in patients with successful reperfusion after mechanical thrombectomy. The location of BBB disruption was not associated with intracranial hemorrhage and poor outcome. Moderate BBB disruption is common after mechanical thrombectomy in a quarter of patients with acute ischemic stroke and increases the risk of intracranial hemorrhage and poor outcome. Copyright © 2018 by the American Society of Neuroimaging.

Mechanisms that Amplify, Attenuate and Deviate Glacier Response to Climate Change in Central East Greenland. (Invited)

NASA Astrophysics Data System (ADS)

Jiskoot, H.

2013-12-01

A multidecadal review of glacier fluctuations and case-studies of glacier processes and environments in central East Greenland will be used to demonstrate Mechanisms that Amplify, Attenuate and Deviate glacier response to climate forcings (MAAD). The different spatial and temporal scales at which MAAD affect mass balance and ice flow may complicate interpretation and longterm extrapolation of glacier response to climate change. A framework of MAAD characterisation and best-practice for interpreting climate signals while taking into account MAAD will be proposed. Glaciers in the Watkins Bjerge, Geikie Plateau and Stauning Alps regions of central East Greenland (68°-72°N) contain about 50000 km2 of glacierized area peripheral to the Greenland Ice Sheet. Within the region, large north-south and coast-inland climatic gradients, as well as complicated topography and glacier dynamics, result in discrepant glacier behaviour. Average retreat rates have doubled from about 2 to 4 km2 a-1 between the late 20th and early 21st centuries. However, glaciers terminating along the Atlantic coast display two times the retreat, thinning, and acceleration rates compared to glaciers terminating in inland fjords or on land. Despite similar climatic forcing variable glacier behaviour is apparent: individual glacier length change ranges from +57 m a-1 to -428 m a-1, though most retreat -20 to -100 m a-1. Interacting dynamic, mass balance and glacio-morphological mechanisms can amplify, attenuate or deviate glacier response (MAAD) to climate change, thus complicating the climatological interpretation of glacier length, area, and thickness changes. East Greenland MAAD include a range of common positive and negative feedback mechanisms in surface mass balance and terminus and subglacial boundary conditions affecting ice flow, but also mechanisms that have longterm or delayed effects. Certain MAAD may affect glacier change interpretation on multiple timescales: e.g. surging glaciers do not

Early warning and response system (EWARS) for dengue outbreaks: Recent advancements towards widespread applications in critical settings.

PubMed

Hussain-Alkhateeb, Laith; Kroeger, Axel; Olliaro, Piero; Rocklöv, Joacim; Sewe, Maquins Odhiambo; Tejeda, Gustavo; Benitez, David; Gill, Balvinder; Hakim, S Lokman; Gomes Carvalho, Roberta; Bowman, Leigh; Petzold, Max

2018-01-01

Dengue outbreaks are increasing in frequency over space and time, affecting people's health and burdening resource-constrained health systems. The ability to detect early emerging outbreaks is key to mounting an effective response. The early warning and response system (EWARS) is a toolkit that provides countries with early-warning systems for efficient and cost-effective local responses. EWARS uses outbreak and alarm indicators to derive prediction models that can be used prospectively to predict a forthcoming dengue outbreak at district level. We report on the development of the EWARS tool, based on users' recommendations into a convenient, user-friendly and reliable software aided by a user's workbook and its field testing in 30 health districts in Brazil, Malaysia and Mexico. 34 Health officers from the 30 study districts who had used the original EWARS for 7 to 10 months responded to a questionnaire with mainly open-ended questions. Qualitative content analysis showed that participants were generally satisfied with the tool but preferred open-access vs. commercial software. EWARS users also stated that the geographical unit should be the district, while access to meteorological information should be improved. These recommendations were incorporated into the second-generation EWARS-R, using the free R software, combined with recent surveillance data and resulted in higher sensitivities and positive predictive values of alarm signals compared to the first-generation EWARS. Currently the use of satellite data for meteorological information is being tested and a dashboard is being developed to increase user-friendliness of the tool. The inclusion of other Aedes borne viral diseases is under discussion. EWARS is a pragmatic and useful tool for detecting imminent dengue outbreaks to trigger early response activities.

Hypertensive response to exercise: mechanisms and clinical implication.

PubMed

Kim, Darae; Ha, Jong-Won

2016-01-01

A hypertensive response to exercise (HRE) is frequently observed in individuals without hypertension or other cardiovascular disease. However, mechanisms and clinical implication of HRE is not fully elucidated. Endothelial dysfunction and increased stiffness of large artery contribute to development of HRE. From neurohormonal aspects, excess stimulation of sympathetic nervous system and augmented rise of angiotensin II seems to be important mechanism in HRE. Increasing evidences indicates that a HRE is associated with functional and structural abnormalities of left ventricle, especially when accompanied by increased central blood pressure. A HRE harbors prognostic significance in future development of hypertension and increased cardiovascular events, particularly if a HRE is documented in moderate intensity of exercise. As supported by previous studies, a HRE is not a benign phenomenon, however, currently, whether to treat a HRE is controversial with uncertain treatment strategy. Considering underlying mechanisms, angiotensin receptor blockers and beta blockers can be suggested in individuals with HRE, however, evidences for efficacy and outcomes of treatment of HRE in individuals without hypertension is scarce and therefore warrants further studies.

Early mobilization and recovery in mechanically ventilated patients in the ICU: a bi-national, multi-centre, prospective cohort study.

PubMed

Hodgson, Carol; Bellomo, Rinaldo; Berney, Susan; Bailey, Michael; Buhr, Heidi; Denehy, Linda; Harrold, Megan; Higgins, Alisa; Presneill, Jeff; Saxena, Manoj; Skinner, Elizabeth; Young, Paul; Webb, Steven

2015-02-26

The aim of this study was to investigate current mobilization practice, strength at ICU discharge and functional recovery at 6 months among mechanically ventilated ICU patients. This was a prospective, multi-centre, cohort study conducted in twelve ICUs in Australia and New Zealand. Patients were previously functionally independent and expected to be ventilated for >48 hours. We measured mobilization during invasive ventilation, sedation depth using the Richmond Agitation and Sedation Scale (RASS), co-interventions, duration of mechanical ventilation, ICU-acquired weakness (ICUAW) at ICU discharge, mortality at day 90, and 6-month functional recovery including return to work. We studied 192 patients (mean age 58.1 ± 15.8 years; mean Acute Physiology and Chronic Health Evaluation (APACHE) (IQR) II score, 18.0 (14 to 24)). Mortality at day 90 was 26.6% (51/192). Over 1,351 study days, we collected information during 1,288 planned early mobilization episodes in patients on mechanical ventilation for the first 14 days or until extubation (whichever occurred first). We recorded the highest level of early mobilization. Despite the presence of dedicated physical therapy staff, no mobilization occurred in 1,079 (84%) of these episodes. Where mobilization occurred, the maximum levels of mobilization were exercises in bed (N = 94, 7%), standing at the bed side (N = 11, 0.9%) or walking (N = 26, 2%). On day three, all patients who were mobilized were mechanically ventilated via an endotracheal tube (N = 10), whereas by day five 50% of the patients mobilized were mechanically ventilated via a tracheostomy tube (N = 18). Early mobilization of patients receiving mechanical ventilation was uncommon. More than 50% of patients discharged from the ICU had developed ICU-acquired weakness, which was associated with death between ICU discharge and day-90. ClinicalTrials.gov NCT01674608. Registered 14 August 2012.

Fluidity of HIV-1-Specific T-Cell Responses during Acute and Early Subtype C HIV-1 Infection and Associations with Early Disease Progression ▿

PubMed Central

Mlotshwa, Mandla; Riou, Catherine; Chopera, Denis; de Assis Rosa, Debra; Ntale, Roman; Treunicht, Florette; Woodman, Zenda; Werner, Lise; van Loggerenberg, Francois; Mlisana, Koleka; Abdool Karim, Salim; Williamson, Carolyn; Gray, Clive M.

2010-01-01

Deciphering immune events during early stages of human immunodeficiency virus type 1 (HIV-1) infection is critical for understanding the course of disease. We characterized the hierarchy of HIV-1-specific T-cell gamma interferon (IFN-γ) enzyme-linked immunospot (ELISPOT) assay responses during acute subtype C infection in 53 individuals and associated temporal patterns of responses with disease progression in the first 12 months. There was a diverse pattern of T-cell recognition across the proteome, with the recognition of Nef being immunodominant as early as 3 weeks postinfection. Over the first 6 months, we found that there was a 23% chance of an increased response to Nef for every week postinfection (P = 0.0024), followed by a nonsignificant increase to Pol (4.6%) and Gag (3.2%). Responses to Env and regulatory proteins appeared to remain stable. Three temporal patterns of HIV-specific T-cell responses could be distinguished: persistent, lost, or new. The proportion of persistent T-cell responses was significantly lower (P = 0.0037) in individuals defined as rapid progressors than in those progressing slowly and who controlled viremia. Almost 90% of lost T-cell responses were coincidental with autologous viral epitope escape. Regression analysis between the time to fixed viral escape and lost T-cell responses (r = 0.61; P = 0.019) showed a mean delay of 14 weeks after viral escape. Collectively, T-cell epitope recognition is not a static event, and temporal patterns of IFN-γ-based responses exist. This is due partly to viral sequence variation but also to the recognition of invariant viral epitopes that leads to waves of persistent T-cell immunity, which appears to associate with slower disease progression in the first year of infection. PMID:20826686

A gene expression profile indicative of early stage HER2 targeted therapy response

PubMed Central

2013-01-01

Background Efficacious application of HER2-targetting agents requires the identification of novel predictive biomarkers. Lapatinib, afatinib and neratinib are tyrosine kinase inhibitors (TKIs) of HER2 and EGFR growth factor receptors. A panel of breast cancer cell lines was treated with these agents, trastuzumab, gefitinib and cytotoxic therapies and the expression pattern of a specific panel of genes using RT-PCR was investigated as a potential marker of early drug response to HER2-targeting therapies. Results Treatment of HER2 TKI-sensitive SKBR3 and BT474 cell lines with lapatinib, afatinib and neratinib induced an increase in the expression of RB1CC1, ERBB3, FOXO3a and NR3C1. The response directly correlated with the degree of sensitivity. This expression pattern switched from up-regulated to down-regulated in the HER2 expressing, HER2-TKI insensitive cell line MDAMB453. Expression of the CCND1 gene demonstrated an inversely proportional response to drug exposure. A similar expression pattern was observed following the treatment with both neratinib and afatinib. These patterns were retained following exposure to traztuzumab and lapatinib plus capecitabine. In contrast, gefitinib, dasatinib and epirubicin treatment resulted in a completely different expression pattern change. Conclusions In these HER2-expressing cell line models, lapatinib, neratinib, afatinib and trastuzumab treatment generated a characteristic and specific gene expression response, proportionate to the sensitivity of the cell lines to the HER2 inhibitor. Characterisation of the induced changes in expression levels of these genes may therefore give a valuable, very early predictor of the likely extent and specificity of tumour HER2 inhibitor response in patients, potentially guiding more specific use of these agents. PMID:23816254

Early detection of response to radiation therapy in patients with brain malignancies using conventional and high b-value diffusion-weighted magnetic resonance imaging.

PubMed

Mardor, Yael; Pfeffer, Raphael; Spiegelmann, Roberto; Roth, Yiftach; Maier, Stephan E; Nissim, Ouzi; Berger, Raanan; Glicksman, Ami; Baram, Jacob; Orenstein, Arie; Cohen, Jack S; Tichler, Thomas

2003-03-15

To study the feasibility of using diffusion-weighted magnetic resonance imaging (DWMRI), which is sensitive to the diffusion of water molecules in tissues, for detection of early tumor response to radiation therapy; and to evaluate the additional information obtained from high DWMRI, which is more sensitive to low-mobility water molecules (such as intracellular or bound water), in increasing the sensitivity to response. Standard MRI and DWMRI were acquired before and at regular intervals after initiating radiation therapy for 10 malignant brain lesions in eight patients. One week posttherapy, three of six responding lesions showed an increase in the conventional DWMRI parameters. Another three responding lesions showed no change. Four nonresponding lesions showed a decrease or no change. The early change in the diffusion parameters was enhanced by using high DWMRI. When high DWMRI was used, all responding lesions showed increase in the diffusion parameter and all nonresponding lesions showed no change or decrease. Response was determined by standard MRI 7 weeks posttherapy. The changes in the diffusion parameters measured 1 week after initiating treatment were correlated with later tumor response or no response (P <.006). This correlation was increased to P <.0006 when high DWMRI was used. The significant correlation between changes in diffusion parameters 1 week after initiating treatment and later tumor response or no response suggests the feasibility of using DWMRI for early, noninvasive prediction of tumor response. The ability to predict response may enable early termination of treatment in nonresponding patients, prevent additional toxicity, and allow for early changes in treatment.

Mechanical stress regulation of plant growth and development

NASA Technical Reports Server (NTRS)

Mitchell, C. A.; Myers, P. N.

1995-01-01

The authors introduce the chapter with a discussion of lessons from nature, agriculture, and landscapes; terms and definitions; and an historical perspective of mechanical stress regulation of plant growth and development. Topics include developmental responses to mechanical stress; mechanical stress-environment interactions; metabolic, productivity, and compositional changes; hormonal involvement; mechanoperception and early transduction mechanisms; applications in agriculture; and research implications. The discussion of hormonal involvement in mechanical stress physiology includes ethylene, auxin, gibberellins, and other phytohormones. The discussion of applications in agriculture examines windbreaks, nursery practices, height control and conditioning, and enhancement of growth and productivity. Implications for research are related to handling plant materials, space biology, and future research needs.

Structural Influence on the Mechanical Response of Adolescent Gottingen Porcine Cranial Bone

DTIC Science & Technology

2016-10-01

specimens were then loaded in quasi -static compression to measure their mechanical response. The surface strain distribution on the specimen face was...13 Fig. 10 Apparent stress-strain responses of a sample of specimens loaded in quasi -static compression...modulus-BVF experimental results shown in Fig. 15 ..................................................................................19 Fig. 17 The

Instability mechanisms and early warning indicators for mesophilic anaerobic digestion of vegetable waste.

PubMed

Li, Dong; Chen, Lin; Liu, Xiaofeng; Mei, Zili; Ren, Haiwei; Cao, Qin; Yan, Zhiying

2017-12-01

In order to elucidate the instability mechanism, screen early warning indicators, and propose control measures, the mesophilic digestion of vegetable waste (VW) was carried out at organic loading rates (OLR) of 0.5, 1.0, and 1.5g volatile solid (VS)/(Ld). The process parameters, including biogas components, volatile fatty acids (VFA), ammonia, pH, total alkalinity (TA), bicarbonate alkalinity (BA), and intermediate alkalinity (IA), were monitored every day. Digestion was inhibited at OLR of 1.5gVS/(Ld). The primary causes of instability are a high sugar and negligible ammonia content, in addition to the feed without effluent recirculation, which led to BA loss. The ratios of CH 4 /CO 2 , VFA/BA, propionate, n-butyrate and iso-valerate were selected as early warning indicators. In order to maintain the digestion of VW at a high OLR, control measures including effluent recirculation and trace element addition are recommended. Copyright © 2017 Elsevier Ltd. All rights reserved.

Jasmonate signaling is activated in the very early stages of iron deficiency responses in rice roots.

PubMed

Kobayashi, Takanori; Itai, Reiko Nakanishi; Senoura, Takeshi; Oikawa, Takaya; Ishimaru, Yasuhiro; Ueda, Minoru; Nakanishi, Hiromi; Nishizawa, Naoko K

2016-07-01

Under low iron availability, plants induce the expression of various genes involved in iron uptake and translocation at the transcriptional level. This iron deficiency response is affected by various plant hormones, but the roles of jasmonates in this response are not well-known. We investigated the involvement of jasmonates in rice iron deficiency responses. High rates of jasmonate-inducible genes were induced during the very early stages of iron deficiency treatment in rice roots. Many jasmonate-inducible genes were also negatively regulated by the ubiquitin ligases OsHRZ1 and OsHRZ2 and positively regulated by the transcription factor IDEF1. Ten out of 35 genes involved in jasmonate biosynthesis and signaling were rapidly induced at 3 h of iron deficiency treatment, and this induction preceded that of known iron deficiency-inducible genes involved in iron uptake and translocation. Twelve genes involved in jasmonate biosynthesis and signaling were also upregulated in HRZ-knockdown roots. Endogenous concentrations of jasmonic acid and jasmonoyl isoleucine tended to be rapidly increased in roots in response to iron deficiency treatment, whereas these concentrations were higher in HRZ-knockdown roots under iron-sufficient conditions. Analysis of the jasmonate-deficient cpm2 mutant revealed that jasmonates repress the expression of many iron deficiency-inducible genes involved in iron uptake and translocation under iron sufficiency, but this repression is partly canceled under an early stage of iron deficiency. These results indicate that jasmonate signaling is activated during the very early stages of iron deficiency, which is partly regulated by IDEF1 and OsHRZs.

Right ventricular pressure response to exercise in adults with isolated ventricular septal defect closed in early childhood.

PubMed

Moller, Thomas; Lindberg, Harald; Lund, May Brit; Holmstrom, Henrik; Dohlen, Gaute; Thaulow, Erik

2018-06-01

We previously demonstrated an abnormally high right ventricular systolic pressure response to exercise in 50% of adolescents operated on for isolated ventricular septal defect. The present study investigated the prevalence of abnormal right ventricular systolic pressure response in 20 adult (age 30-45 years) patients who underwent surgery for early ventricular septal defect closure and its association with impaired ventricular function, pulmonary function, or exercise capacity. The patients underwent cardiopulmonary tests, including exercise stress echocardiography. Five of 19 patients (26%) presented an abnormal right ventricular systolic pressure response to exercise ⩾ 52 mmHg. Right ventricular systolic function was mixed, with normal tricuspid annular plane systolic excursion and fractional area change, but abnormal tricuspid annular systolic motion velocity (median 6.7 cm/second) and isovolumetric acceleration (median 0.8 m/second2). Left ventricular systolic and diastolic function was normal at rest as measured by the peak systolic velocity of the lateral wall and isovolumic acceleration, early diastolic velocity, and ratio of early diastolic flow to tissue velocity, except for ejection fraction (median 53%). The myocardial performance index was abnormal for both the left and right ventricle. Peak oxygen uptake was normal (mean z score -0.4, 95% CI -2.8-0.3). There was no association between an abnormal right ventricular systolic pressure response during exercise and right or left ventricular function, pulmonary function, or exercise capacity. Abnormal right ventricular pressure response is not more frequent in adult patients compared with adolescents. This does not support the theory of progressive pulmonary vascular disease following closure of left-to-right shunts.

Analytical modeling of the mechanics of early invasion of a merozoite into a human erythrocyte.

PubMed

Abdalrahman, Tamer; Franz, Thomas

2017-12-01

In this study, we used a continuum model based on contact mechanics to understand the mechanics of merozoite invasion into human erythrocytes. This model allows us to evaluate the indentation force and work as well as the contact pressure between the merozoite and erythrocyte for an early stage of invasion (γ = 10%). The model predicted an indentation force of 1.3e -11 N and an indentation work of 1e -18 J. The present analytical model can be considered as a useful tool not only for investigations in mechanobiology and biomechanics but also to explore novel therapeutic targets for malaria and other parasite infections.

Discrimination of amygdala response predicts future separation anxiety in youth with early deprivation.

PubMed

Green, Shulamite A; Goff, Bonnie; Gee, Dylan G; Gabard-Durnam, Laurel; Flannery, Jessica; Telzer, Eva H; Humphreys, Kathryn L; Louie, Jennifer; Tottenham, Nim

2016-10-01

mechanism to explain the associations between early caregiving adversity and individual differences in internalizing symptomology during development, thereby contributing to individualized predictions of future clinical outcomes. © 2016 Association for Child and Adolescent Mental Health.

Quantitative Evaluation of Tumor Early Response to a Vascular-Disrupting Agent with Dynamic PET.

PubMed

Guo, Ning; Zhang, Fan; Zhang, Xiaomeng; Guo, Jinxia; Lang, Lixin; Kiesewetter, Dale O; Niu, Gang; Li, Quanzheng; Chen, Xiaoyuan

2015-12-01

The purpose of this study is to evaluate the early response of tumors to a vascular-disrupting agent (VDA) VEGF121/recombinant toxin gelonin (rGel) using dynamic [(18)F]FPPRGD2 positron emission tomography (PET) and kinetic parameter estimation. Two tumor xenograft models: U87MG (highly vascularized) and A549 (moderately vascularized), were selected, and both were randomized into treatment and control groups. Sixty-minute dynamic PET scans with [(18)F]FPPRGD2 that targets to integrin αvβ3 were performed at days 0 (baseline), 1, and 3 since VEGF121/rGel treatment started. Dynamic PET-derived binding potential (BPND) and parametric maps were compared with tumor uptake (%ID/g) and the static PET image at 1 h after the tracer administration. The growth of U87MG tumor was obviously delayed upon VEGF121/rGel treatment. A549 tumor was not responsive to the same treatment. BPND of treated U87MG tumors decreased significantly at day 1 (p < 0.05), and the difference was more significant at day 3 (p < 0.01), compared with the control group. However, the tracer uptake (%ID/g) derived from static images at 1-h time point did not show significant difference between the treated and control tumors until day 3. Little difference in tracer uptake (%ID/g) or BPND was found between treated and control A549 tumors. Considering the tracer retention in tumor and the slower clearance due to damaged tumor vasculature after treatment, BPND representing the actual specific binding portion appears to be more sensitive and accurate than the semiquantitative parameters (such as %ID/g) derived from static images to assess the early response of tumor to VDA treatment. Quantitative analysis based on dynamic PET with [(18)F]FPPRGD2 shows advantages in distinguishing effective from ineffective treatment during the course of VEGF121/rGel therapy at early stage and is therefore more sensitive in assessing therapy response than static PET.

Early and delayed long-term transcriptional changes and short-term transient responses during cold acclimation in olive leaves

PubMed Central

Leyva-Pérez, María de la O; Valverde-Corredor, Antonio; Valderrama, Raquel; Jiménez-Ruiz, Jaime; Muñoz-Merida, Antonio; Trelles, Oswaldo; Barroso, Juan Bautista; Mercado-Blanco, Jesús; Luque, Francisco

2015-01-01

Low temperature severely affects plant growth and development. To overcome this constraint, several plant species from regions having a cool season have evolved an adaptive response, called cold acclimation. We have studied this response in olive tree (Olea europaea L.) cv. Picual. Biochemical stress markers and cold-stress symptoms were detected after the first 24 h as sagging leaves. After 5 days, the plants were found to have completely recovered. Control and cold-stressed plants were sequenced by Illumina HiSeq 1000 paired-end technique. We also assembled a new olive transcriptome comprising 157,799 unigenes and found 6,309 unigenes differentially expressed in response to cold. Three types of response that led to cold acclimation were found: short-term transient response, early long-term response, and late long-term response. These subsets of unigenes were related to different biological processes. Early responses involved many cold-stress-responsive genes coding for, among many other things, C-repeat binding factor transcription factors, fatty acid desaturases, wax synthesis, and oligosaccharide metabolism. After long-term exposure to cold, a large proportion of gene down-regulation was found, including photosynthesis and plant growth genes. Up-regulated genes after long-term cold exposure were related to organelle fusion, nucleus organization, and DNA integration, including retrotransposons. PMID:25324298

Early disaster response in Haiti: the Israeli field hospital experience.

PubMed

Kreiss, Yitshak; Merin, Ofer; Peleg, Kobi; Levy, Gad; Vinker, Shlomo; Sagi, Ram; Abargel, Avi; Bartal, Carmi; Lin, Guy; Bar, Ariel; Bar-On, Elhanan; Schwaber, Mitchell J; Ash, Nachman

2010-07-06

The earthquake that struck Haiti in January 2010 caused an estimated 230,000 deaths and injured approximately 250,000 people. The Israel Defense Forces Medical Corps Field Hospital was fully operational on site only 89 hours after the earthquake struck and was capable of providing sophisticated medical care. During the 10 days the hospital was operational, its staff treated 1111 patients, hospitalized 737 patients, and performed 244 operations on 203 patients. The field hospital also served as a referral center for medical teams from other countries that were deployed in the surrounding areas. The key factor that enabled rapid response during the early phase of the disaster from a distance of 6000 miles was a well-prepared and trained medical unit maintained on continuous alert. The prompt deployment of advanced-capability field hospitals is essential in disaster relief, especially in countries with minimal medical infrastructure. The changing medical requirements of people in an earthquake zone dictate that field hospitals be designed to operate with maximum flexibility and versatility regarding triage, staff positioning, treatment priorities, and hospitalization policies. Early coordination with local administrative bodies is indispensable.

Vaccine-specific antibody secreting cells are a robust early marker of LAIV-induced B-cell response in ferrets.

PubMed

Cherukuri, Anu; Servat, Esteban; Woo, Jennifer

2012-01-05

Currently, a robust set of immune correlates for live attenuated influenza vaccine (LAIV) efficacy in humans has not been fully elucidated. The serum hemagglutination inhibition (HAI) assay has been historically used to measure humoral immune responses to injectable inactivated influenza vaccination. However, serum antibody titers do not reliably reflect the complete mechanism of action of LAIV, which is an intranasally delivered vaccine and is expected to induce local mucosal and cellular immune responses in addition to humoral immune responses. Therefore, we designed a study to evaluate potential immune correlates of LAIV vaccination in the ferret animal model of influenza infection. Ferrets were vaccinated with increasing doses of LAIV and four weeks later challenged with a homologous wild-type (wt) H1N1 strain. Humoral immune responses measured following LAIV vaccination included HAI, serum antibodies and antibody secreting cells (ASC); and the responses were found to correlate with the dose level of LAIV administered in this model. Protection from wt virus challenge was determined by measuring inhibition of wt viral replication in nasal washes and in lung tissue. Results demonstrated that LAIV doses ≥ 5.0 log(10) Plaque Forming Units (PFU) elicited vaccine-specific IgG and IgA ASC frequencies and induced complete protection in the lungs. Further, we developed a novel model utilizing seropositive older ferrets to demonstrate that in the background of previous wt influenza infection LAIV induces a robust vaccine-specific B-cell response even in the absence of serum antibody response, a result that suggests that effector B-cell responses generated by LAIV are not inhibited by prior viral exposure. Finally, we demonstrated that LAIV elicits strain-specific memory B-cell responses that are measurable in a background of wt influenza infections. Taken together, results from these studies identified the antigen-specific ASC frequency as a useful early biomarker of

Airway Humidification Reduces the Inflammatory Response During Mechanical Ventilation.

PubMed

Jiang, Min; Song, Jun-Jie; Guo, Xiao-Li; Tang, Yong-Lin; Li, Hai-Bo

2015-12-01

Currently, no clinical or animal studies have been performed to establish the relationship between airway humidification and mechanical ventilation-induced lung inflammatory responses. Therefore, an animal model was established to better define this relationship. Rabbits (n = 40) were randomly divided into 6 groups: control animals, sacrificed immediately after anesthesia (n = 2); dry gas group animals, subjected to mechanical ventilation for 8 h without humidification (n = 6); and experimental animals, subjected to mechanical ventilation for 8 h under humidification at 30, 35, 40, and 45°C, respectively (n = 8). Inflammatory cytokines in the bronchi alveolar lavage fluid (BALF) were measured. The integrity of the airway cilia and the tracheal epithelium was examined by scanning and transmission electron microscopy, respectively. Peripheral blood white blood cell counts and the wet to dry ratio and lung pathology were determined. Dry gas group animals showed increased tumor necrosis factor alpha levels in BALF compared with control animals (P < .05). The tumor necrosis factor alpha and interleukin-8 levels in the BALF reached baseline levels when the humidification temperature was increased to 40°C. Scanning and transmission electron microscopy analysis revealed that cilia integrity was maintained in the 40°C groups. Peripheral white blood cell counts were not different among those groups. Compared with control animals, the wet to dry ratio was significantly elevated in the dry gas group (P < .05). Moreover, humidification at 40°C resulted in reduced pathologic injury compared with the other groups based on the histologic score. Pathology and reduced inflammation observed in animals treated at 40°C was similar to that observed in the control animals, suggesting that appropriate humidification reduced inflammatory responses elicited as a consequence of mechanical ventilation, in addition to reducing damage to the cilia and reducing water loss in the airway

Rheological and Mechanical Response Modifications for a Self-Leveling Mortar

NASA Astrophysics Data System (ADS)

Katsiadramis, N. J.; Sotiropoulou, A. B.; Pandermarakis, Z. G.

2010-06-01

In many cases cement based materials demand a higher flowability and workability and this conventionally can’t be done without loss of its strength, due to the fact that the common practice to increase the workability is the addition of water. But, nowadays using a third generation superplasticizer (SP) we can achieve the desire flowability without loss of its strength. The action of superplastisizers is to spread efficiently the cement grains and so to wetting better the cement grains giving a more homogeneous mixture with higher strength. Nine different mixtures were prepared adding a small percentage of SP (1%). The conditions to get a self levelling mortar, have to do not only with rheological but also with mechanical demands. The bending and compression test gave the achieving mechanical strength whereas their rheological response came through slump flow and v-funnel flow tests. With the help of a small amount of stabilizer we obtain a robust mixture that deserves the desire response at the field too.

Response of the human tympanic membrane to transient acoustic and mechanical stimuli: Preliminary results.

PubMed

Razavi, Payam; Ravicz, Michael E; Dobrev, Ivo; Cheng, Jeffrey Tao; Furlong, Cosme; Rosowski, John J

2016-10-01

The response of the tympanic membrane (TM) to transient environmental sounds and the contributions of different parts of the TM to middle-ear sound transmission were investigated by measuring the TM response to global transients (acoustic clicks) and to local transients (mechanical impulses) applied to the umbo and various locations on the TM. A lightly-fixed human temporal bone was prepared by removing the ear canal, inner ear, and stapes, leaving the incus, malleus, and TM intact. Motion of nearly the entire TM was measured by a digital holography system with a high speed camera at a rate of 42 000 frames per second, giving a temporal resolution of <24 μs for the duration of the TM response. The entire TM responded nearly instantaneously to acoustic transient stimuli, though the peak displacement and decay time constant varied with location. With local mechanical transients, the TM responded first locally at the site of stimulation, and the response spread approximately symmetrically and circumferentially around the umbo and manubrium. Acoustic and mechanical transients provide distinct and complementary stimuli for the study of TM response. Spatial variations in decay and rate of spread of response imply local variations in TM stiffness, mass, and damping. Copyright © 2016 Elsevier B.V. All rights reserved.

Response of the human tympanic membrane to transient acoustic and mechanical stimuli: Preliminary results

PubMed Central

Razavi, Payam; Ravicz, Michael E.; Dobrev, Ivo; Cheng, Jeffrey Tao; Furlong, Cosme; Rosowski, John J.

2016-01-01

The response of the tympanic membrane (TM) to transient environmental sounds and the contributions of different parts of the TM to middle-ear sound transmission were investigated by measuring the TM response to global transients (acoustic clicks) and to local transients (mechanical impulses) applied to the umbo and various locations on the TM. A lightly-fixed human temporal bone was prepared by removing the ear canal, inner ear, and stapes, leaving the incus, malleus, and TM intact. Motion of nearly the entire TM was measured by a digital holography system with a high speed camera at a rate of 42 000 frames per second, giving a temporal resolution of <24 μs for the duration of the TM response. The entire TM responded nearly instantaneously to acoustic transient stimuli, though the peak displacement and decay time constant varied with location. With local mechanical transients, the TM responded first locally at the site of stimulation, and the response spread approximately symmetrically and circumferentially around the umbo and manubrium. Acoustic and mechanical transients provide distinct and complementary stimuli for the study of TM response. Spatial variations in decay and rate of spread of response imply local variations in TM stiffness, mass, and damping. PMID:26880098

Early warning and response system (EWARS) for dengue outbreaks: Recent advancements towards widespread applications in critical settings

PubMed Central

Kroeger, Axel; Olliaro, Piero; Rocklöv, Joacim; Sewe, Maquins Odhiambo; Tejeda, Gustavo; Benitez, David; Gill, Balvinder; Hakim, S. Lokman; Gomes Carvalho, Roberta; Bowman, Leigh; Petzold, Max

2018-01-01

Background Dengue outbreaks are increasing in frequency over space and time, affecting people’s health and burdening resource-constrained health systems. The ability to detect early emerging outbreaks is key to mounting an effective response. The early warning and response system (EWARS) is a toolkit that provides countries with early-warning systems for efficient and cost-effective local responses. EWARS uses outbreak and alarm indicators to derive prediction models that can be used prospectively to predict a forthcoming dengue outbreak at district level. Methods We report on the development of the EWARS tool, based on users’ recommendations into a convenient, user-friendly and reliable software aided by a user’s workbook and its field testing in 30 health districts in Brazil, Malaysia and Mexico. Findings 34 Health officers from the 30 study districts who had used the original EWARS for 7 to 10 months responded to a questionnaire with mainly open-ended questions. Qualitative content analysis showed that participants were generally satisfied with the tool but preferred open-access vs. commercial software. EWARS users also stated that the geographical unit should be the district, while access to meteorological information should be improved. These recommendations were incorporated into the second-generation EWARS-R, using the free R software, combined with recent surveillance data and resulted in higher sensitivities and positive predictive values of alarm signals compared to the first-generation EWARS. Currently the use of satellite data for meteorological information is being tested and a dashboard is being developed to increase user-friendliness of the tool. The inclusion of other Aedes borne viral diseases is under discussion. Conclusion EWARS is a pragmatic and useful tool for detecting imminent dengue outbreaks to trigger early response activities. PMID:29727447

40 CFR 56.5 - Mechanisms for fairness and uniformity-Responsibilities of Regional Office employees.

Code of Federal Regulations, 2011 CFR

2011-07-01

...-Responsibilities of Regional Office employees. 56.5 Section 56.5 Protection of Environment ENVIRONMENTAL PROTECTION AGENCY (CONTINUED) AIR PROGRAMS (CONTINUED) REGIONAL CONSISTENCY § 56.5 Mechanisms for fairness and uniformity—Responsibilities of Regional Office employees. (a) Each responsible official in a Regional Office...

40 CFR 56.5 - Mechanisms for fairness and uniformity-Responsibilities of Regional Office employees.

Code of Federal Regulations, 2010 CFR

2010-07-01

...-Responsibilities of Regional Office employees. 56.5 Section 56.5 Protection of Environment ENVIRONMENTAL PROTECTION AGENCY (CONTINUED) AIR PROGRAMS (CONTINUED) REGIONAL CONSISTENCY § 56.5 Mechanisms for fairness and uniformity—Responsibilities of Regional Office employees. (a) Each responsible official in a Regional Office...

Inhibition of Connexin 43 Hemichannel-Mediated ATP Release Attenuates Early Inflammation During the Foreign Body Response

PubMed Central

Calder, Bennett W.; Rhett, Joshua Matthew; Bainbridge, Heather; Fann, Stephen A.; Gourdie, Robert G.

2015-01-01

Background: In the last 50 years, the use of medical implants has increased dramatically. Failure of implanted devices and biomaterials is a significant source of morbidity and increasing healthcare expenditures. An important cause of implant failure is the host inflammatory response. Recent evidence implicates extracellular ATP as an important inflammatory signaling molecule. A major pathway for release of cytoplasmic ATP into the extracellular space is through connexin hemichannels, which are the unpaired constituents of gap junction intercellular channels. Blockade of hemichannels of the connexin 43 (Cx43) isoform has been shown to reduce inflammation and improve healing. We have developed a Cx43 mimetic peptide (JM2) that targets the microtubule-binding domain of Cx43. The following report investigates the role of the Cx43 microtubule-binding domain in extracellular ATP release by Cx43 hemichannels and how this impacts early inflammatory events of the foreign body reaction. Methods: In vitro Cx43 hemichannel-mediated ATP release by cultured human microvascular endothelial cells subjected to hypocalcemic and normocalcemic conditions was measured after application of JM2 and the known hemichannel blocker, flufenamic acid. A submuscular silicone implant model was used to investigate in vivo ATP signaling during the early foreign body response. Implants were coated with control pluronic vehicle or pluronic carrying JM2, ATP, JM2+ATP, or known hemichannel blockers and harvested at 24 h for analysis. Results: JM2 significantly inhibited connexin hemichannel-mediated ATP release from cultured endothelial cells. Importantly, the early inflammatory response to submuscular silicone implants was inhibited by JM2. The reduction in inflammation by JM2 was reversed by the addition of exogenous ATP to the pluronic vehicle. Conclusions: These data indicate that ATP released through Cx43 hemichannels into the vasculature is an important signal driving the early inflammatory

Inhibition of connexin 43 hemichannel-mediated ATP release attenuates early inflammation during the foreign body response.

PubMed

Calder, Bennett W; Matthew Rhett, Joshua; Bainbridge, Heather; Fann, Stephen A; Gourdie, Robert G; Yost, Michael J

2015-06-01

In the last 50 years, the use of medical implants has increased dramatically. Failure of implanted devices and biomaterials is a significant source of morbidity and increasing healthcare expenditures. An important cause of implant failure is the host inflammatory response. Recent evidence implicates extracellular ATP as an important inflammatory signaling molecule. A major pathway for release of cytoplasmic ATP into the extracellular space is through connexin hemichannels, which are the unpaired constituents of gap junction intercellular channels. Blockade of hemichannels of the connexin 43 (Cx43) isoform has been shown to reduce inflammation and improve healing. We have developed a Cx43 mimetic peptide (JM2) that targets the microtubule-binding domain of Cx43. The following report investigates the role of the Cx43 microtubule-binding domain in extracellular ATP release by Cx43 hemichannels and how this impacts early inflammatory events of the foreign body reaction. In vitro Cx43 hemichannel-mediated ATP release by cultured human microvascular endothelial cells subjected to hypocalcemic and normocalcemic conditions was measured after application of JM2 and the known hemichannel blocker, flufenamic acid. A submuscular silicone implant model was used to investigate in vivo ATP signaling during the early foreign body response. Implants were coated with control pluronic vehicle or pluronic carrying JM2, ATP, JM2+ATP, or known hemichannel blockers and harvested at 24 h for analysis. JM2 significantly inhibited connexin hemichannel-mediated ATP release from cultured endothelial cells. Importantly, the early inflammatory response to submuscular silicone implants was inhibited by JM2. The reduction in inflammation by JM2 was reversed by the addition of exogenous ATP to the pluronic vehicle. These data indicate that ATP released through Cx43 hemichannels into the vasculature is an important signal driving the early inflammatory response to implanted devices. A vital

Mechanical response of CH3NH3PbI3 nanowires

NASA Astrophysics Data System (ADS)

Ćirić, L.; Ashby, K.; Abadie, T.; Spina, M.; Duchamp, M.; Náfrádi, B.; Kollár, M.; Forró, L.; Horváth, E.

2018-03-01

We report a systematic study of the mechanical response of methylammonium lead triiodide CH3NH3PbI3 nanowires by employing bending measurements using atomic force microscope on suspended wires over photo-lithographically patterned channels. Force-deflection curves measured at room temperature give a Young's modulus between 2 and 14 GPa. This broad range of values is attributed to the variations in the microcrystalline texture of halide perovskite nanowires. The mechanical response of a highly crystalline nanowire is linear with force and has a brittle character. The braking modulus of 48 ± 20 MPa corresponds to 100 μm of radius of curvature of the nanowires, rendering them much better structures for flexible devices than spin coated films. The measured moduli decrease rapidly if the NW is exposed to water vapor.

Centrifuge Modeling of the Thermo-Mechanical Response of Energy Foundations

NASA Astrophysics Data System (ADS)

Goode, Joseph Collin, III

This thesis presents the results from a series of centrifuge tests performed to understand the profiles of thermo-mechanical axial strain, axial displacement, and axial stress in semi-floating and end-bearing energy foundations installed in dry Nevada sand and Bonny silt layers during different combinations of mechanical loading and foundation heating. In addition to the construction details for the centrifuge scale-model reinforced concrete energy foundations, the results from 1 g thermo-mechanical characterization tests performed on the foundations to evaluate their mechanical and thermal material properties are presented in this thesis. In general, the centrifuge-scale tests involve application of an axial load to the head of the foundation followed by circulation of a heat exchange fluid through embedded tubing to bring the foundation to a constant temperature. After this point, mechanical loads were applied to the foundation to characterize their thermo-mechanical response. Specifically, loading tests to failure were performed on the semi-floating foundation installed in different soil layers to characterize the impact of temperature on the load-settlement curve, and elastic loading tests were performed on the end-bearing foundation to characterize the impact of temperature on the mobilized side shear distributions. During application of mechanical loads and changes in foundation temperature, the axial strains are measured using embedded strain gages. The soil and foundation temperatures, foundation head movement, and soil surface deformations are also monitored to characterize the thermo-mechanical response of the system. The tests performed in this study were used to investigate different phenomena relevant to the thermo-mechanical response of energy foundations. First, the role of end-restraint boundary conditions in both sand and silt were investigated by comparing the strain distributions for the end-bearing and semi-floating foundations in each soil type

Stress responsiveness and anxiety-like behavior: The early social environment differentially shapes stability over time in a small rodent.

PubMed

Sangenstedt, Susanne; Jaljuli, Iman; Sachser, Norbert; Kaiser, Sylvia

2017-04-01

The early social environment can profoundly affect behavioral and physiological phenotypes. We investigated how male wild cavy offspring, whose mothers had either lived in a stable (SE) or an unstable social environment (UE) during pregnancy and lactation, differed in their anxiety-like behavior and stress responsiveness. At two different time points in life, we tested the offspring's anxiety-like behavior in a dark-light test and their endocrine reaction to challenge in a cortisol reactivity test. Furthermore, we analyzed whether individual traits remained stable over time. There was no effect of the early social environment on anxiety-like behavior and stress responsiveness. However, at an individual level, anxiety-like behavior was stable over time in UE- but not in SE-sons. Stress responsiveness, in turn, was rather inconsistent in UE-sons and temporally stable in SE-sons. Conclusively, we showed for the first time that the early social environment differentially shapes the stability of behavioral and endocrine traits. At first glance, these results may be surprising, but they can be explained by the different functions anxiety-like behavior and stress responsiveness have. Copyright © 2017 Elsevier Inc. All rights reserved.

Early Blindness Results in Developmental Plasticity for Auditory Motion Processing within Auditory and Occipital Cortex

PubMed Central

Jiang, Fang; Stecker, G. Christopher; Boynton, Geoffrey M.; Fine, Ione

2016-01-01

Early blind subjects exhibit superior abilities for processing auditory motion, which are accompanied by enhanced BOLD responses to auditory motion within hMT+ and reduced responses within right planum temporale (rPT). Here, by comparing BOLD responses to auditory motion in hMT+ and rPT within sighted controls, early blind, late blind, and sight-recovery individuals, we were able to separately examine the effects of developmental and adult visual deprivation on cortical plasticity within these two areas. We find that both the enhanced auditory motion responses in hMT+ and the reduced functionality in rPT are driven by the absence of visual experience early in life; neither loss nor recovery of vision later in life had a discernable influence on plasticity within these areas. Cortical plasticity as a result of blindness has generally be presumed to be mediated by competition across modalities within a given cortical region. The reduced functionality within rPT as a result of early visual loss implicates an additional mechanism for cross modal plasticity as a result of early blindness—competition across different cortical areas for functional role. PMID:27458357

Gravitropism and mechanical signaling in plants.

PubMed

Toyota, Masatsugu; Gilroy, Simon

2013-01-01

Mechanical stress is a critical signal affecting morphogenesis and growth and is caused by a large variety of environmental stimuli such as touch, wind, and gravity in addition to endogenous forces generated by growth. On the basis of studies dating from the early 19th century, the plant mechanical sensors and response components related to gravity can be divided into two types in terms of their temporal character: sensors of the transient stress of reorientation (phasic signaling) and sensors capable of monitoring and responding to the extended, continuous gravitropic signal for the duration of the tropic growth response (tonic signaling). In the case of transient stress, changes in the concentrations of ions in the cytoplasm play a central role in mechanosensing and are likely a key component of initial gravisensing. Potential candidates for mechanosensitive channels have been identified in Arabidopsis thaliana and may provide clues to these rapid, ionic gravisensing mechanisms. Continuous mechanical stress, on the other hand, may be sensed by other mechanisms in addition to the rapidly adapting mechnaosensitive channels of the phasic system. Sustaining such long-term responses may be through a network of biochemical signaling cascades that would therefore need to be maintained for the many hours of the growth response once they are triggered. However, classical physiological analyses and recent simulation studies also suggest involvement of the cytoskeleton in sensing/responding to long-term mechanoresponse independently of the biochemical signaling cascades triggered by initial graviperception events.

The early epigenetic response to ozone: impacts on DNA methylation and hydroxymethylation.

EPA Science Inventory

Epigenetics have been increasingly recognized as a mechanism linking environment and gene expression. Despite awareness of the role of DNA methylation and hydroxymethylation as potential drivers of the response to air pollutants, very little work has been performed investigating ...

Prespecified dose-response analysis for A Very Early Rehabilitation Trial (AVERT).

PubMed

Bernhardt, Julie; Churilov, Leonid; Ellery, Fiona; Collier, Janice; Chamberlain, Jan; Langhorne, Peter; Lindley, Richard I; Moodie, Marj; Dewey, Helen; Thrift, Amanda G; Donnan, Geoff

2016-06-07

Our prespecified dose-response analyses of A Very Early Rehabilitation Trial (AVERT) aim to provide practical guidance for clinicians on the timing, frequency, and amount of mobilization following acute stroke. Eligible patients were aged ≥18 years, had confirmed first (or recurrent) stroke, and were admitted to a stroke unit within 24 hours of stroke onset. Patients were randomized to receive very early and frequent mobilization, commencing within 24 hours, or usual care. We used regression analyses and Classification and Regression Trees (CART) to investigate the effect of timing and dose of mobilization on efficacy and safety outcomes, irrespective of assigned treatment group. A total of 2,104 patients were enrolled, of whom 2,083 (99.0%) were followed up at 3 months. We found a consistent pattern of improved odds of favorable outcome in efficacy and safety outcomes with increased daily frequency of out-of-bed sessions (odds ratio [OR] 1.13, 95% confidence interval [CI] 1.09 to 1.18, p < 0.001), keeping time to first mobilization and mobilization amount constant. Increased amount (minutes per day) of mobilization reduced the odds of a good outcome (OR 0.94, 95% CI 0.91 to 0.97, p < 0.001). Session frequency was the most important variable in the CART analysis, after prognostic variables age and baseline stroke severity. These data suggest that shorter, more frequent mobilization early after acute stroke is associated with greater odds of favorable outcome at 3 months when controlling for age and stroke severity. This study provides Class III evidence that shorter, more frequent early mobilization improves the chance of regaining independence after stroke. © 2016 American Academy of Neurology.

Prespecified dose-response analysis for A Very Early Rehabilitation Trial (AVERT)

PubMed Central

Churilov, Leonid; Ellery, Fiona; Collier, Janice; Chamberlain, Jan; Langhorne, Peter; Lindley, Richard I.; Moodie, Marj; Dewey, Helen; Thrift, Amanda G.; Donnan, Geoff

2016-01-01

Objective: Our prespecified dose-response analyses of A Very Early Rehabilitation Trial (AVERT) aim to provide practical guidance for clinicians on the timing, frequency, and amount of mobilization following acute stroke. Methods: Eligible patients were aged ≥18 years, had confirmed first (or recurrent) stroke, and were admitted to a stroke unit within 24 hours of stroke onset. Patients were randomized to receive very early and frequent mobilization, commencing within 24 hours, or usual care. We used regression analyses and Classification and Regression Trees (CART) to investigate the effect of timing and dose of mobilization on efficacy and safety outcomes, irrespective of assigned treatment group. Results: A total of 2,104 patients were enrolled, of whom 2,083 (99.0%) were followed up at 3 months. We found a consistent pattern of improved odds of favorable outcome in efficacy and safety outcomes with increased daily frequency of out-of-bed sessions (odds ratio [OR] 1.13, 95% confidence interval [CI] 1.09 to 1.18, p < 0.001), keeping time to first mobilization and mobilization amount constant. Increased amount (minutes per day) of mobilization reduced the odds of a good outcome (OR 0.94, 95% CI 0.91 to 0.97, p < 0.001). Session frequency was the most important variable in the CART analysis, after prognostic variables age and baseline stroke severity. Conclusion: These data suggest that shorter, more frequent mobilization early after acute stroke is associated with greater odds of favorable outcome at 3 months when controlling for age and stroke severity. Classification of evidence: This study provides Class III evidence that shorter, more frequent early mobilization improves the chance of regaining independence after stroke. PMID:26888985

Tissue responses to low protracted doses of high let radiations or photons - Early and late damage relevant to radio-protective countermeasures

NASA Technical Reports Server (NTRS)

Ainsworth, E. J.; Afzal, S. M. J.; Crouse, D. A.; Hanson, W. R.; Fry, R. J. M.

1989-01-01

Early and late murine tissue responses to single or fractionated low doses of heavy charged particles, fission-spectrum neutrons or gamma rays are considered. Damage to the hematopoietic system is emphasized, but results on acute lethality, host response to challenge with transplanted leukemia cells and life-shortening are presented. Recent studies on protection against early and late effects by aminothiols, prostaglandins, and other compounds are discussed.

Comparative transcriptome analysis of duckweed (Landoltia punctata) in response to cadmium provides insights into molecular mechanisms underlying hyperaccumulation.

PubMed

Xu, Hua; Yu, Changjiang; Xia, Xinli; Li, Mingliang; Li, Huiguang; Wang, Yu; Wang, Shumin; Wang, Congpeng; Ma, Yubin; Zhou, Gongke

2018-01-01

Cadmium (Cd) is a detrimental environmental pollutant. Duckweeds have been considered promising candidates for Cd phytoremediation. Although many physiological studies have been conducted, the molecular mechanisms underlying Cd hyperaccumulation in duckweeds are largely unknown. In this study, clone 6001 of Landoltia punctata, which showed high Cd tolerance, was obtained by large-scale screening of over 200 duckweed clones. Subsequently, its growth, Cd flux, Cd accumulation, and Cd distribution characteristics were investigated. To further explore the global molecular mechanism, a comprehensive transcriptome analysis was performed. For RNA-Seq, samples were treated with 20 μM CdCl 2 for 0, 1, 3, and 6 days. In total, 9,461, 9,847, and 9615 differentially expressed unigenes (DEGs) were discovered between Cd-treated and control (0 day) samples. DEG clustering and enrichment analysis identified several biological processes for coping with Cd stress. Genes involved in DNA repair acted as an early response to Cd, while RNA and protein metabolism would be likely to respond as well. Furthermore, the carbohydrate metabolic flux tended to be modulated in response to Cd stress, and upregulated genes involved in sulfur and ROS metabolism might cause high Cd tolerance. Vacuolar sequestration most likely played an important role in Cd detoxification in L. punctata 6001. These novel findings provided important clues for molecular assisted screening and breeding of Cd hyperaccumulating cultivars for phytoremediation. Copyright © 2017 Elsevier Ltd. All rights reserved.

Mechanical effort predicts the selection of ankle over hip strategies in nonstepping postural responses

PubMed Central

Jonkers, Ilse; De Schutter, Joris; De Groote, Friedl

2016-01-01

Experimental studies have shown that a continuum of ankle and hip strategies is used to restore posture following an external perturbation. Postural responses can be modeled by feedback control with feedback gains that optimize a specific objective. On the one hand, feedback gains that minimize effort have been used to predict muscle activity during perturbed standing. On the other hand, hip and ankle strategies have been predicted by minimizing postural instability and deviation from upright posture. It remains unclear, however, whether and how effort minimization influences the selection of a specific postural response. We hypothesize that the relative importance of minimizing mechanical work vs. postural instability influences the strategy used to restore upright posture. This hypothesis was investigated based on experiments and predictive simulations of the postural response following a backward support surface translation. Peak hip flexion angle was significantly correlated with three experimentally determined measures of effort, i.e., mechanical work, mean muscle activity and metabolic energy. Furthermore, a continuum of ankle and hip strategies was predicted in simulation when changing the relative importance of minimizing mechanical work and postural instability, with increased weighting of mechanical work resulting in an ankle strategy. In conclusion, the combination of experimental measurements and predictive simulations of the postural response to a backward support surface translation showed that the trade-off between effort and postural instability minimization can explain the selection of a specific postural response in the continuum of potential ankle and hip strategies. PMID:27489362

Immunological dynamics associated with rapid virological response during the early phase of type I interferon therapy in patients with chronic hepatitis C.

PubMed

Lee, Jae-Won; Kim, Won; Kwon, Eun-Kyung; Kim, Yuri; Shin, Hyun Mu; Kim, Dong-Hyun; Min, Chan-Ki; Choi, Ji-Yeob; Lee, Won-Woo; Choi, Myung-Sik; Kim, Byeong Gwan; Cho, Nam-Hyuk

2017-01-01

Type I interferons (IFNs) play an important role in antiviral immunity as well as immunopathogenesis of diverse chronic viral infections. However, the precise mechanisms regulating the multifaceted effects of type I IFNs on the immune system and pathological inflammation still remain unclear. In order to assess the immunological dynamics associated with rapid viral clearance in chronic hepatitis C patients during the acute phase of type I IFN therapy, we analyzed multiple parameters of virological and immunological responses in a cohort of 59 Korean hepatitis C patients who received pegylated IFN-α and ribavirin (IFN/RBV). Most of the Korean patients had favorable alleles in the IFN-λ loci for responsiveness to IFN/RBV (i.e., C/C in rs12979860, T/T in rs8099917, and TT/TT in rs368234815). Rapid virological response (RVR) was determined mainly by the hepatitis C virus genotype. Among the cytokines analyzed, higher plasma levels of IL-17A and FGF were observed in non-RVR patients infected with viral genotype 1 and IP-10 was consistently elevated in RVR group infected with genotype 2 during the early phase of antiviral therapy. In addition, these three cytokines were correlated each other, suggesting a functional linkage of the cytokines in antiviral responses during IFN/RBV therapy. A low baseline frequencies of regulatory T cells and γδ T cells, but high level of group 2 innate lymphoid cells, in peripheral bloods were also significantly associated with the RVR group, implicating a potential role of the cellular immunity during the early phase of IFN/RBV therapy. Therefore, the immunological programs established by chronic hepatitis C and rapid disruption of the delicate balance by exogenous type I IFN might be associated with the subsequent virological outcomes in chronic hepatitis C patients.

Immunological dynamics associated with rapid virological response during the early phase of type I interferon therapy in patients with chronic hepatitis C

PubMed Central

Lee, Jae-Won; Kim, Won; Kwon, Eun-Kyung; Kim, Yuri; Shin, Hyun Mu; Kim, Dong-Hyun; Min, Chan-Ki; Choi, Ji-Yeob; Lee, Won-Woo; Choi, Myung-Sik; Kim, Byeong Gwan

2017-01-01

Type I interferons (IFNs) play an important role in antiviral immunity as well as immunopathogenesis of diverse chronic viral infections. However, the precise mechanisms regulating the multifaceted effects of type I IFNs on the immune system and pathological inflammation still remain unclear. In order to assess the immunological dynamics associated with rapid viral clearance in chronic hepatitis C patients during the acute phase of type I IFN therapy, we analyzed multiple parameters of virological and immunological responses in a cohort of 59 Korean hepatitis C patients who received pegylated IFN-α and ribavirin (IFN/RBV). Most of the Korean patients had favorable alleles in the IFN-λ loci for responsiveness to IFN/RBV (i.e., C/C in rs12979860, T/T in rs8099917, and TT/TT in rs368234815). Rapid virological response (RVR) was determined mainly by the hepatitis C virus genotype. Among the cytokines analyzed, higher plasma levels of IL-17A and FGF were observed in non-RVR patients infected with viral genotype 1 and IP-10 was consistently elevated in RVR group infected with genotype 2 during the early phase of antiviral therapy. In addition, these three cytokines were correlated each other, suggesting a functional linkage of the cytokines in antiviral responses during IFN/RBV therapy. A low baseline frequencies of regulatory T cells and γδ T cells, but high level of group 2 innate lymphoid cells, in peripheral bloods were also significantly associated with the RVR group, implicating a potential role of the cellular immunity during the early phase of IFN/RBV therapy. Therefore, the immunological programs established by chronic hepatitis C and rapid disruption of the delicate balance by exogenous type I IFN might be associated with the subsequent virological outcomes in chronic hepatitis C patients. PMID:28614389

Modulation of early cortical processing during divided attention to non-contiguous locations

PubMed Central

Frey, Hans-Peter; Schmid, Anita M.; Murphy, Jeremy W.; Molholm, Sophie; Lalor, Edmund C.; Foxe, John J.

2015-01-01

We often face the challenge of simultaneously attending to multiple non-contiguous regions of space. There is ongoing debate as to how spatial attention is divided under these situations. While for several years the predominant view was that humans could divide the attentional spotlight, several recent studies argue in favor of a unitary spotlight that rhythmically samples relevant locations. Here, this issue was addressed using high-density electrophysiology in concert with the multifocal m-sequence technique to examine visual evoked responses to multiple simultaneous streams of stimulation. Concurrently, we assayed the topographic distribution of alpha-band oscillatory mechanisms, a measure of attentional suppression. Participants performed a difficult detection task that required simultaneous attention to two stimuli in contiguous (undivided) or non-contiguous parts of space. In the undivided condition, the classical pattern of attentional modulation was observed, with increased amplitude of the early visual evoked response and increased alpha amplitude ipsilateral to the attended hemifield. For the divided condition, early visual responses to attended stimuli were also enhanced and the observed multifocal topographic distribution of alpha suppression was in line with the divided attention hypothesis. These results support the existence of divided attentional spotlights, providing evidence that the corresponding modulation occurs during initial sensory processing timeframes in hierarchically early visual regions and that suppressive mechanisms of visual attention selectively target distracter locations during divided spatial attention. PMID:24606564

Transcriptomic Responses During Early Development Following Arsenic Exposure in Western Clawed Frogs, Silurana tropicalis.

PubMed

Zhang, Jing; Koch, Iris; Gibson, Laura A; Loughery, Jennifer R; Martyniuk, Christopher J; Button, Mark; Caumette, Guilhem; Reimer, Kenneth J; Cullen, William R; Langlois, Valerie S

2015-12-01

Arsenic compounds are widespread environmental contaminants and exposure elicits serious health issues, including early developmental anomalies. Depending on the oxidation state, the intermediates of arsenic metabolism interfere with a range of subcellular events, but the fundamental molecular events that lead to speciation-dependent arsenic toxicity are not fully elucidated. This study therefore assesses the impact of arsenic exposure on early development by measuring speciation and gene expression profiles in the developing Western clawed frog (Silurana tropicalis) larvae following the environmental relevant 0.5 and 1 ppm arsenate exposure. Using HPLC-ICP-MS, arsenate, dimethylarsenic acid, arsenobetaine, arsenocholine, and tetramethylarsonium ion were detected. Microarray and pathway analyses were utilized to characterize the comprehensive transcriptomic responses to arsenic exposure. Clustering analysis of expression data showed distinct gene expression patterns in arsenate treated groups when compared with the control. Pathway enrichment revealed common biological themes enriched in both treatments, including cell signal transduction, cell survival, and developmental pathways. Moreover, the 0.5 ppm exposure led to the enrichment of pathways and biological processes involved in arsenic intake or efflux, as well as histone remodeling. These compensatory responses are hypothesized to be responsible for maintaining an in-body arsenic level comparable to control animals. With no appreciable changes observed in malformation and mortality between control and exposed larvae, this is the first study to suggest that the underlying transcriptomic regulations related to signal transduction, cell survival, developmental pathways, and histone remodeling may contribute to maintaining ongoing development while coping with the potential arsenic toxicity in S. tropicalis during early development. © The Author 2015. Published by Oxford University Press on behalf of the

Early detection of disease program: Evaluation of the cellular immune response

NASA Technical Reports Server (NTRS)

Criswell, B. S.; Knight, V.; Martin, R. R.; Kasel, J. A.

1974-01-01

The early cellular responses of specific components of the leukocyte and epithelial cell populations to foreign challenges of both an infectious and noninfectious character were evaluated. Procedures for screening potential flight crews were developed, documented, and tested on a control population. Methods for preparing suitable populations of lymphocytes, polymorphonuclear leukocytes, macrophages, and epithelial cells were first established and evaluated. Epithelial cells from viral infected individuals were screened with a number of anti-viral antisera. This procedure showed the earliest indication of disease as well as providing a specific diagnosis to the physicians. Both macrophages and polymorphonuclear leukocytes were studied from normal individuals, smokers, and patients with viral infections. Newer techniques enabling better definition of lymphocyte subpopulations were then developed, namely the E and EAC rosette procedures for recognition of T (thymus-derived) and B (bone-marrow-derived) lymphocyte subpopulations. Lymphocyte and lymphocyte subpopulation response to multiple mitogens have been evaluated.

3D Computational Mechanics Elucidate the Evolutionary Implications of Orbit Position and Size Diversity of Early Amphibians

PubMed Central

Marcé-Nogué, Jordi; Fortuny, Josep; De Esteban-Trivigno, Soledad; Sánchez, Montserrat; Gil, Lluís; Galobart, Àngel

2015-01-01

For the first time in vertebrate palaeontology, the potential of joining Finite Element Analysis (FEA) and Parametrical Analysis (PA) is used to shed new light on two different cranial parameters from the orbits to evaluate their biomechanical role and evolutionary patterns. The early tetrapod group of Stereospondyls, one of the largest groups of Temnospondyls is used as a case study because its orbits position and size vary hugely within the members of this group. An adult skull of Edingerella madagascariensis was analysed using two different cases of boundary and loading conditions in order to quantify stress and deformation response under a bilateral bite and during skull raising. Firstly, the variation of the original geometry of its orbits was introduced in the models producing new FEA results, allowing the exploration of the ecomorphology, feeding strategy and evolutionary patterns of these top predators. Secondly, the quantitative results were analysed in order to check if the orbit size and position were correlated with different stress patterns. These results revealed that in most of the cases the stress distribution is not affected by changes in the size and position of the orbit. This finding supports the high mechanical plasticity of this group during the Triassic period. The absence of mechanical constraints regarding the orbit probably promoted the ecomorphological diversity acknowledged for this group, as well as its ecological niche differentiation in the terrestrial Triassic ecosystems in clades as lydekkerinids, trematosaurs, capitosaurs or metoposaurs. PMID:26107295

Divergent response of the neritic carbonate factory to environmental changes during the Early Bajocian Event

NASA Astrophysics Data System (ADS)

Bodin, Stephane; Hönig, Martin; Krencker, Francois-Nicolas; Danisch, Jan; Kabiri, Lahcen

2017-04-01

The Early Bajocian witnessed a global environmental perturbation, characterized by faunal and floral turnovers and a positive carbon isotope excursion. In Italy, this environmental perturbation coincided with an eutrophication event and a carbonate crisis, but this has so far not been adequately reported from other settings, leaving doubt about the extent and nature of these phenomena. Here, we are reporting on an extensive neritic carbonate factory demise that occurs in the upper Lower Bajocian of the Central High Atlas of Morocco, more precisely in the upper Propinquans - lower Humphriesianum Zones. This demise coincided with the acme of the global carbon isotope perturbation, recorded by a 3‰ positive carbon isotope excursion in the bulk organic matter of Morocco. Recovery of the neritic carbonate system occurs during the Early to Late Bajocian transition. The duration of the neritic carbonate factory demise was therefore in the order of 1 Myr. Furthermore, we observe that the Lower Bajocian of Morocco is relatively enriched in arenitic siliciclastic deposits, suggesting increased weathering and nutrient levels along the northwestern margin of Africa during the Early Bajocian. However, comparison with neighboring European basins highlights the non-uniqueness and different timing of the response of shallow-water carbonates to the Early Bajocian environmental perturbations, as some regions present no sign of carbonate factory crisis. Hence, we postulate that local factors were important in mediating the response of neritic carbonate factories to this global environmental perturbation. We notably highlight the role of large Early Bajocian sea-level fluctuation as a trigger for carbonate factory change and demise in Morocco. Indeed, in the Central High Atlas Basin, transgressive intervals are seeing the development of a mud-dominated carbonate factory whereas regressive intervals are associated with grain-dominated carbonate factory. We speculate that the

Early divergent host responses in SHIVsf162P3 and SIVmac251 infected macaques correlate with control of viremia.

PubMed

Xu, Huanbin; Wang, Xiaolei; Morici, Lisa A; Pahar, Bapi; Veazey, Ronald S

2011-03-25

We previously showed intravaginal inoculation with SHIVsf162p3 results in transient viremia followed by undetectable viremia in most macaques, and some displayed subsequent immunity to superinfection with pathogenic SIVmac251. Here we compare early T cell activation, proliferation, and plasma cytokine/chemokine responses in macaques intravaginally infected with either SHIVsf162p3 or SIVmac251 to determine whether distinct differences in host responses may be associated with early viral containment. The data show SIVmac251 infection results in significantly higher levels of T cell activation, proliferation, and a mixed cytokine/chemokine "storm" in plasma in primary infection, whereas infection with SHIVsf162p3 resulted in significantly lower levels of T cell activation, proliferation, and better preservation of memory CD4+ T cells in early infection which immediately preceded control of viremia. These results support the hypothesis that early systemic immune activation, T cell proliferation, and a more prominent and broader array of cytokine/chemokine responses facilitate SIV replication, and may play a key role in persistence of infection, and the progression to AIDS. In contrast, immune unresponsiveness may be associated with eventual clearance of virus, a concept that may have key significance for therapy and vaccine design.

Escape is a more common mechanism than avidity reduction for evasion of CD8+ T cell responses in primary human immunodeficiency virus type 1 infection

PubMed Central

2011-01-01

Background CD8+ T cells play an important role in control of viral replication during acute and early human immunodeficiency virus type 1 (HIV-1) infection, contributing to containment of the acute viral burst and establishment of the prognostically-important persisting viral load. Understanding mechanisms that impair CD8+ T cell-mediated control of HIV replication in primary infection is thus of importance. This study addressed the relative extent to which HIV-specific T cell responses are impacted by viral mutational escape versus reduction in response avidity during the first year of infection. Results 18 patients presenting with symptomatic primary HIV-1 infection, most of whom subsequently established moderate-high persisting viral loads, were studied. HIV-specific T cell responses were mapped in each individual and responses to a subset of optimally-defined CD8+ T cell epitopes were followed from acute infection onwards to determine whether they were escaped or declined in avidity over time. During the first year of infection, sequence variation occurred in/around 26/33 epitopes studied (79%). In 82% of cases of intra-epitopic sequence variation, the mutation was confirmed to confer escape, although T cell responses were subsequently expanded to variant sequences in some cases. In contrast, < 10% of responses to index sequence epitopes declined in functional avidity over the same time-frame, and a similar proportion of responses actually exhibited an increase in functional avidity during this period. Conclusions Escape appears to constitute a much more important means of viral evasion of CD8+ T cell responses in acute and early HIV infection than decline in functional avidity of epitope-specific T cells. These findings support the design of vaccines to elicit T cell responses that are difficult for the virus to escape. PMID:21635736

Responsive parenting: establishing early foundations for social, communication, and independent problem-solving skills.

PubMed

Landry, Susan H; Smith, Karen E; Swank, Paul R

2006-07-01

Mothers whose infants varied in early biological characteristics (born at term, n = 120; born at very low birth weight [VLBW], n = 144) were randomized to a target group (n = 133) or developmental feedback comparison group (n = 131) to determine whether learning responsive behaviors would facilitate infant development. The target condition included videotaped examples, problem-solving activities, and mothers' critique of their own behaviors through video procedures across 10 home visits. All target versus comparison mothers showed greater increases across multiple responsiveness behaviors observed in 4 assessments conducted across 6-13 months of age; changes in emotionally supportive behaviors were strongest for target mothers of infants born at VLBW. Increased maternal responsiveness facilitated greater growth in target infants' social, emotional, communication, and cognitive competence, supporting a causal role for responsiveness on infant development. Although benefits were generally comparable across risk groups, aspects of social and emotional skills showed greater change for those born at VLBW. Evidence for responsiveness as a multidimensional construct was provided as well as the importance of different aspects of responsiveness mediating the effect of the intervention on different infant skill domains.

Seasonal greening of an Arctic ecosystem in response to early snowmelt and climate warming: do plant community responses differ from species responses?

NASA Astrophysics Data System (ADS)

Steltzer, H.; Weintraub, M. N.; Sullivan, P.; Wallenstein, M. D.; Schimel, J.; Darrouzet-Nardi, A.; Shory, R.; Livensperger, C.; Melle, C.; Segal, A. D.; Daly, K.; Tsosie, T.

2011-12-01

In the Arctic and around the world, earlier plant growth and a longer growing season are indications that warmer temperatures or other global changes are changing the seasonality of the Earth's ecosystems. These changes in plant life histories have multi-trophic level consequences that affect food webs and biogeochemical cycles. Both the response of the plant community and of individual species can affect food and habitat resources for animals or nutrient resources for microbes. Our aim was to determine if the response of an Arctic plant community differs from individual species responses to climate change. For two years in an early snowmelt and climate warming experiment in moist acidic tussock tundra, we observed the seasonal greening of the ecosystem through near-surface measurements of surface greenness and through direct observations of the timing of plant life history events for five to eight common species that differ in growth form. In 2010 when snowmelt was accelerated by 4 days, earlier snowmelt alone or in combination with climate warming extended the life history of the dominant graminoids (E. vaginatum and C. bigelowii) and willow (S. pulchra) by 3 to 4 days. For these species, new leaf production began earlier, while the timing of senescence was similar to the controls. The effect of earlier snowmelt on the life histories of birch (B. nana) and cranberry (V. vitis-idaea) was less, but warming alone tended to increase life history duration. Warming led to earlier leaf expansion for birch and delayed senescence for cranberry. We found that the onset of greening for the plant community began four days earlier, due to the earlier loss of snow cover, and that warming accelerated the rate of greening. Peak season ended 4 days earlier in response to earlier snowmelt and climate warming, due to earlier senescence by birch. In 2011, our manipulation of the snowpack by increasing energy absorption accelerated snowmelt by 15 days and control plots were snowfree

Perfluorocarbon induces alveolar epithelial cell response through structural and mechanical remodeling.

PubMed

André Dias, Sofia; Planus, Emmanuelle; Angely, Christelle; Lotteau, Luc; Tissier, Renaud; Filoche, Marcel; Louis, Bruno; Pelle, Gabriel; Isabey, Daniel

2018-02-15

During total liquid ventilation, lung cells are exposed to perfluorocarbon (PFC) whose chemophysical properties highly differ from standard aqueous cell feeding medium (DMEM). We herein perform a systematic study of structural and mechanical properties of A549 alveolar epithelial cells in order to characterize their response to PFC exposure, using DMEM as control condition. Changes in F-actin structure, focal adhesion density and glycocalyx distribution are evaluated by confocal fluorescent microscopy. Changes in cell mechanics and adhesion are measured by multiscale magnetic twisting cytometry (MTC). Two different microrheological models (single Voigt and power law) are used to analyze the cell mechanics characterized by cytoskeleton (CSK) stiffness and characteristic relaxation times. Cell-matrix adhesion is analyzed using a stochastic multibond deadhesion model taking into account the non-reversible character of the cell response, allowing us to quantify the adhesion weakness and the number of associated bonds. The roles of F-actin structure and glycocalyx layer are evaluated by depolymerizing F-actin and degrading glycocalyx, respectively. Results show that PFC exposure consistently induces F-actin remodeling, CSK softening and adhesion weakening. These results demonstrate that PFC triggers an alveolar epithelial cell response herein evidenced by a decay in intracellular CSK tension, an adhesion weakening and a glycocalyx layer redistribution. These PFC-induced cell adjustments are consistent with the hypothesis that cells respond to a decrease in adhesion energy at cell surface. This adhesion energy can be even further reduced in the presence of surfactant adsorbed at the cell surface.

Vγ1+γδT, early cardiac infiltrated innate population dominantly producing IL-4, protect mice against CVB3 myocarditis by modulating IFNγ+ T response.

PubMed

Wan, Fangfang; Yan, Kepeng; Xu, Dan; Qian, Qian; Liu, Hui; Li, Min; Xu, Wei

2017-01-01

Viral myocarditis (VMC) is an inflammation of the myocardium closely associated with Coxsackievirus B3 (CVB3) infection. Vγ1 + γδT cells, one of early cardiac infiltrated innate population, were reported to protect CVB3 myocarditis while the precise mechanism not fully addressed. To explore cytokine profiles and kinetics of Vγ1 + γδT and mechanism of protection against VMC, flow cytometry was conducted on cardiac Vγ1 cells in C57BL/6 mice following CVB3 infection. The level of cardiac inflammation, transthoracic echocardiography and viral replication were evaluated after monoclonal antibody depletion of Vγ1γδT. We found that Vγ1 + γδT cells infiltration peaked in the heart at day3 post CVB3 infection and constituted a minor source of IFN-γ but major producers for early IL-4. Vγ1γδT cells were activated earlier holding a higher IL-4-producing efficiency than CD4 + Th cells in the heart. Depletion of Vγ1 + γδT resulted in a significantly exacerbated cardiac infiltration, increased T, macrophage and neutrophil population in heart homogenates and worse cardiomyopathy; which was accompanied by a significant expansion of peripheral IFNγ + CD4+ and CD8+T cells. Neutralization of IL-4 in mice resulted in an exacerbated acute myocarditis confirming the IL-4-mediated protective mechanism of Vγ1. Our findings identify a unique property of Vγ1 + γδT cells as one dominant early producers of IL-4 upon CVB3 acute infection which is a key mediator to protect mice against acute myocarditis by modulating IFNγ-secreting T response. Copyright © 2016 Elsevier Ltd. All rights reserved.

Histogram analysis of apparent diffusion coefficient for monitoring early response in patients with advanced cervical cancers undergoing concurrent chemo-radiotherapy.

PubMed

Meng, Jie; Zhu, Lijing; Zhu, Li; Ge, Yun; He, Jian; Zhou, Zhengyang; Yang, Xiaofeng

2017-11-01

Background Apparent diffusion coefficient (ADC) histogram analysis has been widely used in determining tumor prognosis. Purpose To investigate the dynamic changes of ADC histogram parameters during concurrent chemo-radiotherapy (CCRT) in patients with advanced cervical cancers. Material and Methods This prospective study enrolled 32 patients with advanced cervical cancers undergoing CCRT who received diffusion-weighted (DW) magnetic resonance imaging (MRI) before CCRT, at the end of the second and fourth week during CCRT and one month after CCRT completion. The ADC histogram for the entire tumor volume was generated, and a series of histogram parameters was obtained. Dynamic changes of those parameters in cervical cancers were investigated as early biomarkers for treatment response. Results All histogram parameters except AUC low showed significant changes during CCRT (all P < 0.05). There were three variable trends involving different parameters. The mode, 5th, 10th, and 25th percentiles showed similar early increase rates (33.33%, 33.99%, 34.12%, and 30.49%, respectively) at the end of the second week of CCRT. The pre-CCRT 5th and 25th percentiles of the complete response (CR) group were significantly lower than those of the partial response (PR) group. Conclusion A series of ADC histogram parameters of cervical cancers changed significantly at the early stage of CCRT, indicating their potential in monitoring early tumor response to therapy.

Gene expression profiling reveals underlying molecular mechanisms of the early stages of tamoxifen-induced rat hepatocarcinogenesis

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

Pogribny, Igor P.; Bagnyukova, Tetyana V.; Tryndyak, Volodymyr P.

2007-11-15

Tamoxifen is a widely used anti-estrogenic drug for chemotherapy and, more recently, for the chemoprevention of breast cancer. Despite the indisputable benefits of tamoxifen in preventing the occurrence and re-occurrence of breast cancer, the use of tamoxifen has been shown to induce non-alcoholic steatohepatitis, which is a life-threatening fatty liver disease with a risk of progression to cirrhosis and hepatocellular carcinoma. In recent years, the high-throughput microarray technology for large-scale analysis of gene expression has become a powerful tool for increasing the understanding of the molecular mechanisms of carcinogenesis and for identifying new biomarkers with diagnostic and predictive values. Inmore » the present study, we used the high-throughput microarray technology to determine the gene expression profiles in the liver during early stages of tamoxifen-induced rat hepatocarcinogenesis. Female Fisher 344 rats were fed a 420 ppm tamoxifen containing diet for 12 or 24 weeks, and gene expression profiles were determined in liver of control and tamoxifen-exposed rats. The results indicate that early stages of tamoxifen-induced liver carcinogenesis are characterized by alterations in several major cellular pathways, specifically those involved in the tamoxifen metabolism, lipid metabolism, cell cycle signaling, and apoptosis/cell proliferation control. One of the most prominent changes during early stages of tamoxifen-induced hepatocarcinogenesis is dysregulation of signaling pathways in cell cycle progression from the G{sub 1} to S phase, evidenced by the progressive and sustained increase in expression of the Pdgfc, Calb3, Ets1, and Ccnd1 genes accompanied by the elevated level of the PI3K, p-PI3K, Akt1/2, Akt3, and cyclin B, D1, and D3 proteins. The early appearance of these alterations suggests their importance in the mechanism of neoplastic cell transformation induced by tamoxifen.« less

Early and delayed long-term transcriptional changes and short-term transient responses during cold acclimation in olive leaves.

PubMed

Leyva-Pérez, María de la O; Valverde-Corredor, Antonio; Valderrama, Raquel; Jiménez-Ruiz, Jaime; Muñoz-Merida, Antonio; Trelles, Oswaldo; Barroso, Juan Bautista; Mercado-Blanco, Jesús; Luque, Francisco

2015-02-01

Low temperature severely affects plant growth and development. To overcome this constraint, several plant species from regions having a cool season have evolved an adaptive response, called cold acclimation. We have studied this response in olive tree (Olea europaea L.) cv. Picual. Biochemical stress markers and cold-stress symptoms were detected after the first 24 h as sagging leaves. After 5 days, the plants were found to have completely recovered. Control and cold-stressed plants were sequenced by Illumina HiSeq 1000 paired-end technique. We also assembled a new olive transcriptome comprising 157,799 unigenes and found 6,309 unigenes differentially expressed in response to cold. Three types of response that led to cold acclimation were found: short-term transient response, early long-term response, and late long-term response. These subsets of unigenes were related to different biological processes. Early responses involved many cold-stress-responsive genes coding for, among many other things, C-repeat binding factor transcription factors, fatty acid desaturases, wax synthesis, and oligosaccharide metabolism. After long-term exposure to cold, a large proportion of gene down-regulation was found, including photosynthesis and plant growth genes. Up-regulated genes after long-term cold exposure were related to organelle fusion, nucleus organization, and DNA integration, including retrotransposons. © The Author 2014. Published by Oxford University Press on behalf of Kazusa DNA Research Institute.