Levels of Red Blood Cell Fatty Acids in Patients With Psychosis, Their Unaffected Siblings, and Healthy Controls.

PubMed

Medema, Suzanne; Mocking, Roel J T; Koeter, Maarten W J; Vaz, Frédéric M; Meijer, Carin; de Haan, Lieuwe; van Beveren, Nico J M; Kahn, René; de Haan, Lieuwe; van Os, Jim; Wiersma, Durk; Bruggeman, Richard; Cahn, Wiepke; Meijer, Carin; Myin-Germeys, Inez

2016-03-01

Two recent meta-analyses showed decreased red blood cell (RBC) polyunsaturated fatty acids (FA) in schizophrenia and related disorders. However, both these meta-analyses report considerable heterogeneity, probably related to differences in patient samples between studies. Here, we investigated whether variations in RBC FA are associated with psychosis, and thus may be an intermediate phenotype of the disorder. For the present study, a total of 215 patients (87% outpatients), 187 siblings, and 98 controls were investigated for multiple FA analyses. Based on previous studies, we investigated docosahexaenoic acid (DHA), docosapentaenoic acid (DPA), arachidonic acid (AA), linoleic acid (LA), nervonic acid (NA), and eicasopentaenoic acid (EPA). On an exploratory basis, a large number of additional FA were investigated. Multilevel mixed models were used to compare the FA between the 3 groups. Compared to controls, both patients and siblings showed significantly increased DHA, DPA, AA, and NA. LA was significantly higher in siblings compared to controls. EPA was not significantly different between the 3 groups. Also the exploratory FA were increased in patients and siblings. We found increased RBC FA DHA, DPA, AA, and NA in patients and siblings compared to controls. The direction of change is similar in both patients and siblings, which may suggest a shared environment and/or an intermediate phenotype. Differences between patient samples reflecting stage of disorder, dietary patterns, medication use, and drug abuse are possible modifiers of FA, contributing to the heterogeneity in findings concerning FA in schizophrenia patients. © The Author 2015. Published by Oxford University Press on behalf of the Maryland Psychiatric Research Center. All rights reserved. For permissions, please email: journals.permissions@oup.com.

Food addiction in a Spanish sample of eating disorders: DSM-5 diagnostic subtype differentiation and validation data.

PubMed

Granero, Roser; Hilker, Ines; Agüera, Zaida; Jiménez-Murcia, Susana; Sauchelli, Sarah; Islam, Mohammed A; Fagundo, Ana B; Sánchez, Isabel; Riesco, Nadine; Dieguez, Carlos; Soriano, José; Salcedo-Sánchez, Cristina; Casanueva, Felipe F; De la Torre, Rafael; Menchón, José M; Gearhardt, Ashley N; Fernández-Aranda, Fernando

2014-11-01

Although the concept of 'food addiction' (FA) has raised growing interest because of evidence for similarities between substance dependence and excessive food intake, there is a lack of studies that explore this construct among the wide spectrum of eating disorders (EDs). Besides providing validation scores of a Spanish version of the Yale FA Scale (YFAS-S), this study examined the prevalence of 'FA' among ED subtypes compared with healthy-eating controls (HCs) and the association between 'FA' scores, eating symptomatology and general psychopathology. A sample of 125 adult women with ED, diagnosed according to Diagnostic and Statistical Manual of Mental Disorders 5 criteria, and 82 healthy-eating women participated in the study. All participants were assessed with the YFAS-S, the ED Inventory-2 and the Symptom Checklist-Revised. Results showed that the internal structure of the one-dimensional solution for the YFAS-S was very good (α = 0.95). The YFAS-S has a good discriminative capacity to differentiate between ED and controls (specificity = 97.6% and sensitivity (Se) = 72.8%; area under receiver operating characteristic curve = 0.90) and a good Se to screen for specific ED subtypes. YFAS-S scores were associated with higher levels of negative affect and depression, higher general psychopathology, more severe eating pathology and greater body mass index. When comparing the prevalence of 'FA' between ED subtypes, the lowest prevalence of 'FA', measured with the YFAS-S, was for the anorexia nervosa (AN) restrictive subtype with 50%, and the highest was for the AN binge-purging subtype (85.7%), followed by bulimia nervosa (81.5%) and binge eating disorder (76.9%). In conclusion, higher YFAS-S scores are associated with bingeing ED-subtype patients and with more eating severity and psychopathology. Although the 'FA' construct is able to differentiate between ED and HC, it needs to be further explored. Copyright © 2014 John Wiley & Sons, Ltd and Eating Disorders Association.

Validation of the French Version of the DSM-5 Yale Food Addiction Scale in a Nonclinical Sample

PubMed Central

Courtois, Robert; Gearhardt, Ashley N.; Gaillard, Philippe; Journiac, Kevin; Cathelain, Sarah; Réveillère, Christian; Ballon, Nicolas

2016-01-01

Objective: The Yale Food Addiction Scale (YFAS) is the only questionnaire that assesses food addiction (FA) based on substance dependence criteria in the Diagnostic and Statistical Manual of Mental Disorders (DSM), Fourth Edition, Text Revision. Following recent updating of addiction criteria, a new DSM-5 version (YFAS 2.0) has been developed. Our study tested the psychometric properties of the French YFAS 2.0 in a nonclinical population. Method: We assessed 330 nonclinical participants for FA (French YFAS 2.0), eating behaviour, and eating disorder (Binge Eating Scale, Emotional Overeating Questionnaire, Three-Factor Eating Questionnaire-R18, Questionnaire on Eating and Weight Patterns-Revised, Eating Disorder Diagnostic Scale). We tested the scale’s factor structure (confirmatory factor analysis based on 11 diagnostic criteria), internal consistency, and construct and incremental validity. Results: Prevalence of FA was 8.2%. Our results supported a 1-factor structure similar to the US version. In both its diagnostic and symptom count versions, the YFAS 2.0 had good internal consistency (Kuder-Richardson alpha was 0.83) and was associated with body mass index (BMI), binge eating, uncontrolled and emotional eating, binge eating disorder, and cognitive restraint. FA predicted BMI above and beyond binge eating frequency. Females had a higher prevalence of FA than males but not more FA symptoms. Conclusions: We validated a psychometrically sound French version of the YFAS 2.0 in a nonclinical population, in both its symptom count and diagnostic versions. Future studies should investigate psychometric properties of this questionnaire in clinical populations potentially at risk for FA (that is, patients with obesity, diabetes, hypertension, or other metabolic syndrome risk factors). PMID:28212499

Validation of the French Version of the DSM-5 Yale Food Addiction Scale in a Nonclinical Sample.

PubMed

Brunault, Paul; Courtois, Robert; Gearhardt, Ashley N; Gaillard, Philippe; Journiac, Kevin; Cathelain, Sarah; Réveillère, Christian; Ballon, Nicolas

2017-03-01

The Yale Food Addiction Scale (YFAS) is the only questionnaire that assesses food addiction (FA) based on substance dependence criteria in the Diagnostic and Statistical Manual of Mental Disorders (DSM), Fourth Edition, Text Revision. Following recent updating of addiction criteria, a new DSM-5 version (YFAS 2.0) has been developed. Our study tested the psychometric properties of the French YFAS 2.0 in a nonclinical population. We assessed 330 nonclinical participants for FA (French YFAS 2.0), eating behaviour, and eating disorder (Binge Eating Scale, Emotional Overeating Questionnaire, Three-Factor Eating Questionnaire-R18, Questionnaire on Eating and Weight Patterns-Revised, Eating Disorder Diagnostic Scale). We tested the scale's factor structure (confirmatory factor analysis based on 11 diagnostic criteria), internal consistency, and construct and incremental validity. Prevalence of FA was 8.2%. Our results supported a 1-factor structure similar to the US version. In both its diagnostic and symptom count versions, the YFAS 2.0 had good internal consistency (Kuder-Richardson alpha was 0.83) and was associated with body mass index (BMI), binge eating, uncontrolled and emotional eating, binge eating disorder, and cognitive restraint. FA predicted BMI above and beyond binge eating frequency. Females had a higher prevalence of FA than males but not more FA symptoms. We validated a psychometrically sound French version of the YFAS 2.0 in a nonclinical population, in both its symptom count and diagnostic versions. Future studies should investigate psychometric properties of this questionnaire in clinical populations potentially at risk for FA (that is, patients with obesity, diabetes, hypertension, or other metabolic syndrome risk factors).

Food addiction as a proxy for eating disorder and obesity severity, trauma history, PTSD symptoms, and comorbidity.

PubMed

Brewerton, Timothy D

2017-06-01

Food addiction (FA) is a newly defined yet still controversial condition that has important etiological, developmental, treatment, prevention, and social policy implications. In this review, the case is made that FA (or high scores on the Yale Food Addiction Scale) may be used as a proxy measure for a matrix of interrelated clinical features, including greater eating disorder severity, greater obesity severity, more severe trauma histories, greater symptoms of posttraumatic stress disorder (PTSD), greater psychiatric comorbidity, as well as greater medical morbidity and mortality. A Medline search was undertaken using the following terms: food addiction cross-referenced with eating disorders (anorexia nervosa, bulimia nervosa, binge eating disorder, and binge eating), obesity, trauma, posttraumatic stress disorder, and comorbidity. The thesis is that the identification and acknowledgment of the concept of FA, when integrated into an overall, trauma-focused and transdiagnostic treatment approach, are supported and can be useful in understanding clinically the "big picture." Food addiction (FA) may be used as a proxy for (1) bulimic eating disorder severity, (2) complex trauma histories, (3) severity of PTSD and PTSD symptoms, (4) intensity of psychiatric comorbidity, (5) severity of obesity, as well as (6) their combination. Implications for developing treatment strategies are discussed. The case for a comprehensive management that requires careful attention to medical and psychiatric assessment and integrated care that incorporates trauma-focused treatment is made.

Investigation of moisture-induced embrittlement of iron aluminides. Interim report

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

Castagna, A.; Stoloff, N.S.

Alloy FA-129 undergoes an increase in crack propagation rate and a loss of fracture toughness in moisture-bearing and hydrogen gas environments. A similar effect is seen on ductility of FA-129 in tensile tests. The embrittling effect in air is attributed to oxidation of aluminum in the alloy by water vapor to produce Al{sub 2}O{sub 3} and hydrogen gas. Alloy FAP-Y, which is disordered and contains only 16 a%Al is embrittled by hydrogen gas in a manner similar to that of FA-129. However, laboratory air had little effect on the crack growth rates, fracture toughness, or tensile ductility. The lower aluminummore » content apparently is insufficient to induce the Al-H{sub 2}O reaction. TEM and SEM analyses of microstructure and fracture surfaces were consistent with the change in fracture toughness with order and environment. Testing at elevated temperatures reduces crack growth rates in FA-129, and increases fracture toughness and ductility. This is consistent with the well documented peak in hydrogen embrittlement in structural alloys at or near room temperature. Elevated temperature affects the degree of embrittlement in a complex manner, possibly changing the rates of several of the processes involved.« less

Surface-coated fly ash reinforced biodegradable poly(vinyl alcohol) composite films: part 2-analysis and characterization

NASA Astrophysics Data System (ADS)

Nath, D. C. D.; Bandyopadhyay, S.; Campbell, J.; Yu, A.; Blackburn, D.; White, C.

2010-12-01

Composite films of poly(vinyl alcohol) (PVA) reinforced with 5, 10, 15, 20 and 25 wt.% surface-coated fly ash by surfactant, sodium lauryl sulphate (SLS-FA) along with 1 wt.% cross-linking agent, glutaraldehyde (GLA) were prepared by aqueous casting method. The tensile strengths of the composite films were increased proportionally with the addition of SLS-FA. The maximum 75% higher strength of the composite with 20 wt.% was achieved compared to that of neat PVA. The modulus of the composites was also increased proportionally with SLS-FA and the maximum 218% reached in composite with 20 wt.%, but the strain at break was decreased with addition of SLS-FA. Changes in FTIR spectra reflect the chemical and/or physical bonding in the ternary PVA, SLS-FA and GLA component systems. In the study of surface morphology, the connectivity was visualized in SEM images along with interstitial voids. The films with SLS-FA show 53% smoother surface calculated with AFM compared to unmodified FA composite films.

Synthesis and characterization of covalent diphenylalanine nanotube-folic acid conjugates

NASA Astrophysics Data System (ADS)

Castillo, John J.; Rindzevicius, Tomas; Wu, Kaiyu; Schmidt, Michael S.; Janik, Katarzyna A.; Boisen, Anja; Svendsen, Winnie; Rozlosnik, Noemi; Castillo-León, Jaime

2014-07-01

Herein, we describe the synthesis and characterization of a covalent nanoscale assembly formed between diphenylalanine micro/nanotubes (PNT) and folic acid (FA). The conjugate was obtained via chemical functionalization through coupling of amine groups of PNTs and carboxylic groups of FA. The surface analysis of PNT-FA indicated the presence of FA aggregates on the surface of PNTs. The covalent interaction between FA and self-assembled PNTs was further investigated using fluorescence microscopy, Raman and surface-enhanced Raman scattering (SERS) spectroscopies. The SERS experiments were performed on a large area silver-capped (diameter of 62 nm) silicon nanopillars with an approximate height of 400 nm and a width of 200 nm. The results showed that the PNT-FA synthesis procedure preserves the molecular structure of FA. The PNT-FA conjugate presented in this study is a promising candidate for applications in the detection and diagnosis of cancer or tropical diseases such as leishmaniasis and as a carrier nanosystem delivering drugs to malignant tumors that overexpress folate receptors.

White Matter Integrity Reductions in Intermittent Explosive Disorder

PubMed Central

Lee, Royce; Arfanakis, Konstantinos; Evia, Arnold M; Fanning, Jennifer; Keedy, Sarah; Coccaro, Emil F

2016-01-01

Intermittent explosive disorder (IED), as described in DSM-5, is the categorical expression of pathological impulsive aggression. Previous work has identified neurobiological correlates of the disorder in patterns of frontal-limbic brain activity and dysregulation of serotonergic neurotransmission. Given the importance of short- and-long range white matter connections of the brain in social and emotional behavior, studies of white matter connectivity in impulsive aggression are warranted. Diffusion tensor imaging (DTI) studies in the related conditions of antisocial and borderline personality disorder have produced preliminary evidence of disturbed white matter connectivity in these disorders, but to date there have been no DTI studies in IED. A total of 132 male and female adults between the ages of 18 and 55 years underwent Turboprop-DTI on a 3-Tesla MRI scanner. Of these, 42 subjects had IED, 40 were normal controls, and 50 were clinical psychiatric controls with psychiatric disorders without IED. All subjects were free of alcohol, psychotropic medications, or drugs of abuse. The diffusion tensor was calculated in each voxel and maps of fractional anisotropy (FA) were generated. Tract-based spatial statistics (TBSS) were used to compare FA along the white matter skeleton among the three subject groups. IED was associated with lower FA in two clusters located in the superior longitudinal fasciculus (SLF) when compared with the psychiatric and healthy controls. Impulsive aggression and borderline personality disorder, but not psychopathy or antisocial personality disorder, was associated with lower FA in the two clusters within the SLF. In conclusion, IED was associated with lower white matter integrity in long-range connections between the frontal and temporoparietal regions. PMID:27206265

White Matter Integrity Reductions in Intermittent Explosive Disorder.

PubMed

Lee, Royce; Arfanakis, Konstantinos; Evia, Arnold M; Fanning, Jennifer; Keedy, Sarah; Coccaro, Emil F

2016-10-01

Intermittent explosive disorder (IED), as described in DSM-5, is the categorical expression of pathological impulsive aggression. Previous work has identified neurobiological correlates of the disorder in patterns of frontal-limbic brain activity and dysregulation of serotonergic neurotransmission. Given the importance of short- and-long range white matter connections of the brain in social and emotional behavior, studies of white matter connectivity in impulsive aggression are warranted. Diffusion tensor imaging (DTI) studies in the related conditions of antisocial and borderline personality disorder have produced preliminary evidence of disturbed white matter connectivity in these disorders, but to date there have been no DTI studies in IED. A total of 132 male and female adults between the ages of 18 and 55 years underwent Turboprop-DTI on a 3-Tesla MRI scanner. Of these, 42 subjects had IED, 40 were normal controls, and 50 were clinical psychiatric controls with psychiatric disorders without IED. All subjects were free of alcohol, psychotropic medications, or drugs of abuse. The diffusion tensor was calculated in each voxel and maps of fractional anisotropy (FA) were generated. Tract-based spatial statistics (TBSS) were used to compare FA along the white matter skeleton among the three subject groups. IED was associated with lower FA in two clusters located in the superior longitudinal fasciculus (SLF) when compared with the psychiatric and healthy controls. Impulsive aggression and borderline personality disorder, but not psychopathy or antisocial personality disorder, was associated with lower FA in the two clusters within the SLF. In conclusion, IED was associated with lower white matter integrity in long-range connections between the frontal and temporoparietal regions.

A COMPREHENSIVE EXAMINATION OF WHITE MATTER TRACTS AND CONNECTOMETRY IN MAJOR DEPRESSIVE DISORDER

PubMed Central

Delaparte, Lauren; Yeh, Fang‐Cheng; DeLorenzo, Christine; McGrath, Patrick J.; Weissman, Myrna M.; Adams, Phillip; Fava, Maurizio; Deckersbach, Thilo; McInnis, Melvin G.; Carmody, Thomas J.; Cooper, Crystal M.; Kurian, Benji T.; Lu, Hanzhang; Toups, Marisa S.; Trivedi, Madhukar H.; Parsey, Ramin V.

2015-01-01

Background Major depressive disorder (MDD) is a debilitating disorder characterized by widespread brain abnormalities. The literature is mixed as to whether or not white matter abnormalities are associated with MDD. This study sought to examine fractional anisotropy (FA) in white matter tracts in individuals with MDD using diffusion tensor imaging (DTI). Methods 139 participants with MDD and 39 healthy controls (HC) in a multisite study were included. DTI scans were acquired in 64 directions and FA was determined in the brain using four methods: region of interest (ROI), tract‐based spatial statistics (TBSS), and diffusion tractography. Diffusion connectometry was used to identify white matter pathways associated with MDD. Results There were no significant differences when comparing FA in MDD and HC groups using any method. In the MDD group, there was a significant relationship between depression severity and FA in the right medial orbitofrontal cortex, and between age of onset of MDD and FA in the right caudal anterior cingulate cortex using the ROI method. There was a significant relationship between age of onset and connectivity in the thalamocortical radiation, inferior longitudinal fasciculus, and cerebellar tracts using diffusion connectometry. Conclusions The lack of group differences in FA and connectometry analysis may result from the clinically heterogenous nature of MDD. However, the relationship between FA and depression severity may suggest a state biomarker of depression that should be investigated as a potential indicator of response. Age of onset may also be a significant clinical feature to pursue when studying white matter tracts. PMID:26477532

Surface-coated fly ash used as filler in biodegradable poly(vinyl alcohol) composite films: Part 1—The modification process

NASA Astrophysics Data System (ADS)

Nath, D. C. D.; Bandyopadhyay, S.; Gupta, S.; Yu, A.; Blackburn, D.; White, C.

2010-02-01

The surfaces of fly ash (FA) particles were modified by surfactant, sodium lauryl sulphate (SLS) and used in fabrication of composite films with polyvinyl alcohol (PVA). Both unmodified fly ash (FA) and modified fly ash (SLS-FA) samples were examined using a range of analytical tools including X-ray fluorescence spectroscopy (XRF), scanning electron microscopy (SEM), transmission electron microscopy (TEM), Fourier transform infrared (FTIR) and X-ray photoelectron spectroscopy (XPS). The distribution patterns of SLS-FA particles were shifted to the higher regions compared to FA by adding 1.2-4.2 μm in the ranges between 2 and 25 μm, whereas the modification process reduced the size of the particles over 25 μm due to grinding during the activation process. The increased 1.2-4.2 μm in average can be considered the thickness of the surfactant on the SLS-FA surface. On the oxides based chemical analysis by XRF, the compositions were almost unchanged. SEM and TEM were visualised the irregular sizes morphology mostly spherical of the particles, although it is impossible to capture the images of exactly same particles in modified and unmodified forms. The composite films reinforced with SLS-FA showed 33% higher strength than those of FA filled films. The enhancement of tensile strength attributed from the level of physical bonding between SLS-FA and PVA surfaces.

The bee microbiome: impact on bee health and model for evolution and ecology of host-microbe interactions

USDA-ARS?s Scientific Manuscript database

Fanconi anemia (FA) is a rare genetic disorder caused by defects in DNA damage repair. FA patients often develop squamous cell carcinoma (SCC) at sites where high-risk human papillomaviruses (HPVs) are known to cause cancer, including the cervix. However, SCCs found in human FA patients are often HP...

Self-assembly of fatty acids on hydroxylated Al surface and effects of their stability on wettability and nanoscale organization.

PubMed

Liascukiene, Irma; Steffenhagen, Marie; Asadauskas, Svajus J; Lambert, Jean-François; Landoulsi, Jessem

2014-05-27

The self-assembly of fatty acids (FA) on the surfaces of inorganic materials is a relevant way to control their wetting properties. While the mechanism of adsorption on model flat substrate is well described in the literature, interfacial processes remain poorly documented on nanostructured surfaces. In this study, we report the self-assembly of a variety of FA on a hydroxylated Al surface which exhibits a random nanoscale organization. Our results revealed a peculiar fingerprint due to the FA self-assembly which consists in the formation of aligned nanopatterns in a state of hierarchical nanostructuration, regardless of the molecular structure of the FA (chain length, level of unsaturation). After a significant removal of adsorbed FA using UV/O3 treatment, a complete wetting was reached, and a noticeable disturbance of the surface morphology was observed, evidencing the pivotal role of FA molecules to maintain these nanostructures. The origin of wetting properties was investigated prior to and after conditioning of FA-modified samples taking into account key parameters, namely the surface roughness and its composition. For this purpose, the Wenzel roughness, defined as the third moment of power spectral density, was used, as it is sensitive to high spatial frequency and thus to the obtained hierarchical level of nanostructuration. Our results revealed that no correlation can be made between water contact angles (θ(w)) and the Wenzel roughness. By contrast, θ(w) strongly increased with the amount of -CHx- groups exhibited by adsorbed FA. These findings suggest that the main origin of hydrophobization is the presence of self-assembled molecules and that the surface roughness has only a small contribution to the wettability.

Immune Thrombocytopenia in Two Unrelated Fanconi Anemia Patients – A Mere Coincidence?

PubMed Central

Karastaneva, Anna; Lanz, Sofia; Wawer, Angela; Behrends, Uta; Schindler, Detlev; Dietrich, Ralf; Burdach, Stefan; Urban, Christian; Benesch, Martin; Seidel, Markus G.

2015-01-01

Thrombocytopenia and pancytopenia, occurring in patients with Fanconi anemia (FA), are interpreted either as progression to bone marrow failure or as developing myelodysplasia. On the other hand, immune thrombocytopenia (ITP) represents an acquired and often self-limiting benign hematologic disorder, associated with peripheral, immune-mediated, platelet destruction requiring different management modalities than those used in congenital bone marrow failure syndromes, including FA. Here, we describe the clinical course of two independent FA patients with atypical – namely immune – thrombocytopenia. While in one patient belonging to complementation group FA-A, the ITP started at 17 months of age and showed a chronically persisting course with severe purpura, responding well to intravenous immunoglobulins (IVIG) and later also danazol, a synthetic androgen, the other patient (of complementation group FA-D2) had a self-limiting course that resolved after one administration of IVIG. No cytogenetic aberrations or bone marrow abnormalities other than FA-typical mild dysplasia were detected. Our data show that acute and chronic ITP may occur in FA patients and impose individual diagnostic and therapeutic challenges in this rare congenital bone marrow failure/tumor predisposition syndrome. The management and a potential context of immune pathogenesis with the underlying marrow disorder are discussed. PMID:26106590

[Molecular basis of Fanconi's anemia].

PubMed

Digweed, M

1999-01-01

Fanconi anaemia (FA) is an autosomal recessive genetic disorder characterised clinically by progressive bone marrow failure, skeletal deformities and a predisposition to neoplasia. Patient cells manifest an extreme chromosomal instability and hypersensitivity to polyfunctional alkylating agents. It is assumed that the basic defect is related to the repair of DNA damage, in particular that of so-called DNA crosslinks. Currently there are eight complementation groups in FA (FA-A-FA-H) which indicates that at least eight independent genes can lead to FA. Three of these genes have been identified: FANCA, FANCC and FANCG. In this review, the molecular biology and genetics of FA are presented and possible functions of the FANC proteins are discussed.

Fanconi anemia and the cell cycle: new perspectives on aneuploidy

PubMed Central

2014-01-01

Fanconi anemia (FA) is a complex heterogenic disorder of genomic instability, bone marrow failure, cancer predisposition, and congenital malformations. The FA signaling network orchestrates the DNA damage recognition and repair in interphase as well as proper execution of mitosis. Loss of FA signaling causes chromosome instability by weakening the spindle assembly checkpoint, disrupting centrosome maintenance, disturbing resolution of ultrafine anaphase bridges, and dysregulating cytokinesis. Thus, the FA genes function as guardians of genome stability throughout the cell cycle. This review discusses recent advances in diagnosis and clinical management of Fanconi anemia and presents the new insights into the origins of genomic instability in FA. These new discoveries may facilitate the development of rational therapeutic strategies for FA and for FA-deficient malignancies in the general population. PMID:24765528

The relationship among food addiction, negative mood, and eating-disordered behaviors in patients seeking to have bariatric surgery.

PubMed

Koball, Afton M; Clark, Matthew M; Collazo-Clavell, Maria; Kellogg, Todd; Ames, Gretchen; Ebbert, Jon; Grothe, Karen B

2016-01-01

Food addiction (FA) may be related to poor weight loss outcomes; however, the literature on food addiction in bariatric surgery-seeking populations is limited. The aim of the present study was to identify the prevalence of FA in a bariatric surgery-seeking population and its association with mood, problematic eating behaviors, and substance use. The relationship between prebariatric surgery food addiction screening and postsurgical outcomes was assessed. Academic medical center. Adult outpatients (n = 923) seeking bariatric surgery underwent psychological evaluation between January 2012 and May 2014. Patients were administered the Yale Food Addiction Scale (YFAS) to assess FA. Of the original sample, 195 patients underwent Roux-en-Y gastric bypass surgery. Patients returned for medical follow-up at 6 (n = 169) and 12 (n = 113) months postsurgery; 26 (13%) patients at 6 months and 82 (42%) patients at 12 months were lost to follow-up or had not reached 1 year postsurgery. Fourteen percent of patients met FA criteria. Patients positive for FA were more likely to endorse greater levels of depression, anxiety, binge eating episodes, nighttime eating syndrome, and low eating self-efficacy. No relationship was observed between FA and current substance use. FA did not predict postoperative outcomes including weight loss, rehospitalization, or attendance at follow-up medical appointments. FA is related to psychological distress and eating disordered behaviors among bariatric patients. However, FA was not predictive of short-term (6-12 mo) bariatric surgery outcomes. Future research should determine how FA affects long-term postoperative outcomes and mood stability. Copyright © 2016 American Society for Bariatric Surgery. Published by Elsevier Inc. All rights reserved.

White matter integrity in major depressive disorder: Implications of childhood trauma, 5-HTTLPR and BDNF polymorphisms.

PubMed

Tatham, Erica L; Ramasubbu, Rajamannar; Gaxiola-Valdez, Ismael; Cortese, Filomeno; Clark, Darren; Goodyear, Bradley; Foster, Jane; Hall, Geoffrey B

2016-07-30

This study examined the impact of childhood neglect, serotonin transporter (5-HTTLPR) and brain derived neurotrophic factor (BDNF) polymorphisms on white matter (WM) integrity in major depressive disorder (MDD) using diffusion tensor imaging (DTI). Fifty-five medication-free MDD patients and 18 controls underwent diffusion tensor imaging scanning, genotyping and completed the Childhood Trauma Questionnaire. Tract based spatial statistics (TBSS) findings revealed reduced fractional anisotropy (FA) in the MDD group in the anterior internal capsule. 5-HTTLPR-S'L' heterozygotes in the MDD group exhibited reduced FA in the internal capsule relative to S'S' and reduced FA in corona radiata compared to L'L'. Probabilistic tractography revealed higher FA in the uncinate fasciculus (UF) for BDNF val/val genotype relative to met-carriers, particularly in individuals with high depression severity. High depression severity and experiences of childhood physical or emotional neglect predicted higher FA in the UF and superior longitudinal fasciculus. Reductions in FA were identified for subgroups of MDD patients who were 5-HTTLPR heterozygotes and BDNF-met carriers. An association between emotional/physical neglect and FA was observed in subjects with high depressive symptoms. Our findings suggest that WM connectivity within frontal and limbic regions are affected by depression and influenced by experiences of neglect and genetic risk factors. Copyright © 2016 Elsevier Ireland Ltd. All rights reserved.

The influence of comorbid oppositional defiant disorder on white matter microstructure in attention-deficit/hyperactivity disorder.

PubMed

van Ewijk, Hanneke; Noordermeer, Siri D S; Heslenfeld, Dirk J; Luman, Marjolein; Hartman, Catharina A; Hoekstra, Pieter J; Faraone, Stephen V; Franke, Barbara; Buitelaar, Jan K; Oosterlaan, J

2016-07-01

Attention-deficit/hyperactivity disorder (ADHD) and oppositional defiant disorder (ODD) are highly comorbid disorders. ADHD has been associated with altered white matter (WM) microstructure, though the literature is inconsistent, which may be due to differences in the in- or exclusion of participants with comorbid ODD. WM abnormalities in ODD are still poorly understood, and it is unclear whether comorbid ODD in ADHD may have confounded the current ADHD literature. Diffusion Tensor Imaging (DTI) was used to compare fractional anisotropy (FA) and mean diffusivity (MD) between ADHD patients with (n = 42) and without (n = 117) comorbid ODD. All participants were between 8-25 years and groups did not differ in mean age or gender. Follow-up analyses were conducted to examine the role of antisocial behaviour (conduct problems) on FA and MD values in both groups. Comorbid ODD in ADHD was associated with lower FA in left frontotemporal WM, which appeared independent of ADHD symptoms. FA was negatively associated with antisocial behaviour in ADHD + ODD, but not in ADHD-only. Comorbid ODD is associated with WM abnormalities in individuals with ADHD, which appears to be independent of ADHD symptoms. Altered WM microstructure in comorbid ODD may play a role in inconsistencies in the current DTI literature in ADHD. Altered development of these tracts may contribute to social-emotional and cognitive problems in children with oppositional and antisocial behaviour.

Effect of fulvic acid surface coatings on plutonium sorption and desorption kinetics on goethite

DOE PAGES

Tinnacher, Ruth M.; Begg, James D.; Mason, Harris; ...

2015-01-21

The rates and extent of plutonium (Pu) sorption and desorption onto mineral surfaces are important parameters for predicting Pu mobility in subsurface environments. The presence of natural organic matter, such as fulvic acid (FA), may influence these parameters. We investigated the effects of FA on Pu(IV) sorption/desorption onto goethite in two scenarios: when FA was (1) initially present in solution or (2) found as organic coatings on the mineral surface. A low pH was used to maximize FA coatings on goethite. Experiments were combined with kinetic modeling and speciation calculations to interpret variations in Pu sorption rates in the presencemore » of FA. Our results indicate that FA can change the rates and extent of Pu sorption onto goethite at pH 4. Differences in the kinetics of Pu sorption were observed as a function of the concentration and initial form of FA. The fraction of desorbed Pu decreased in the presence of FA, indicating that organic matter can stabilize sorbed Pu on goethite. These results suggest that ternary Pu–FA–mineral complexes could enhance colloid-facilitated Pu transport. In conclusion, more representative natural conditions need to be investigated to quantify the relevance of these findings.« less

Effects of oxidative stress on fatty acid- and one-carbon-metabolism in psychiatric and cardiovascular disease comorbidity

PubMed Central

Assies, J; Mocking, R J T; Lok, A; Ruhé, H G; Pouwer, F; Schene, A H

2014-01-01

Objective Cardiovascular disease (CVD) is the leading cause of death in severe psychiatric disorders (depression, schizophrenia). Here, we provide evidence of how the effects of oxidative stress on fatty acid (FA) and one-carbon (1-C) cycle metabolism, which may initially represent adaptive responses, might underlie comorbidity between CVD and psychiatric disorders. Method We conducted a literature search and integrated data in a narrative review. Results Oxidative stress, mainly generated in mitochondria, is implicated in both psychiatric and cardiovascular pathophysiology. Oxidative stress affects the intrinsically linked FA and 1-C cycle metabolism: FAs decrease in chain length and unsaturation (particularly omega-3 polyunsaturated FAs), and lipid peroxidation products increase; the 1-C cycle shifts from the methylation to transsulfuration pathway (lower folate and higher homocysteine and antioxidant glutathione). Interestingly, corresponding alterations were reported in psychiatric disorders and CVD. Potential mechanisms through which FA and 1-C cycle metabolism may be involved in brain (neurocognition, mood regulation) and cardiovascular system functioning (inflammation, thrombosis) include membrane peroxidizability and fluidity, eicosanoid synthesis, neuroprotection and epigenetics. Conclusion While oxidative-stress-induced alterations in FA and 1-C metabolism may initially enhance oxidative stress resistance, persisting chronically, they may cause damage possibly underlying (co-occurrence of) psychiatric disorders and CVD. This might have implications for research into diagnosis and (preventive) treatment of (CVD in) psychiatric patients. PMID:24649967

Assessment of white matter abnormalities in paranoid schizophrenia and bipolar mania patients.

PubMed

Cui, Liqian; Chen, Zhuangfei; Deng, Wei; Huang, Xiaoqi; Li, Mingli; Ma, Xiaohong; Huang, Chaohua; Jiang, Lijun; Wang, Yingcheng; Wang, Qiang; Collier, David A; Gong, Qiyong; Li, Tao

2011-12-30

White matter abnormalities have been repeatedly reported in both schizophrenia and bipolar disorder (BD) in diffusion tensor imaging (DTI) studies, but the empirical evidence about the diagnostic specificity of white matter abnormalities in these disorders is still limited. This study sought to investigate the alterations in fractional anisotropy (FA) in white matter throughout the entire brain of patients from Chengdu, China with paranoid schizophrenia and bipolar mania. For this purpose, DTI was used to assess white matter integrity in patients with paranoid schizophrenia (n=25) and psychotic bipolar mania (n=18) who had been treated with standard pharmacotherapy for fewer than 5 days at the time of study, as well as in normal controls (n=30). The differences in FA were measured by use of voxel-based analysis. The results show that reduced FA was found in the left posterior corona radiata (PCR) in patients with psychotic bipolar mania and paranoid schizophrenia compared to the controls. Patients with psychotic bipolar mania also showed a significant reduction in FA in right posterior corona radiata and in right anterior thalamic radiation (ATR). A direct comparison between the two patient groups found no significant differences in any regions, and none of the findings were associated with illness duration. Correlation analysis indicated that FA values showed a significant negative correlation with positive symptom scores on the Positive and Negative Syndrome Scale in the left frontal-parietal lobe in the paranoid schizophrenia. It was concluded that common abnormalities in the left PCR might imply an overlap in white matter pathology in the two disorders and might be related to shared risk factors for the two disorders. 2011 Elsevier Ireland Ltd. All rights reserved.

Genetic Study of White Matter Integrity in UK Biobank (N=8448) and the Overlap With Stroke, Depression, and Dementia.

PubMed

Rutten-Jacobs, Loes C A; Tozer, Daniel J; Duering, Marco; Malik, Rainer; Dichgans, Martin; Markus, Hugh S; Traylor, Matthew

2018-06-01

Structural integrity of the white matter is a marker of cerebral small vessel disease, which is the major cause of vascular dementia and a quarter of all strokes. Genetic studies provide a way to obtain novel insights in the disease mechanism underlying cerebral small vessel disease. The aim was to identify common variants associated with microstructural integrity of the white matter and to elucidate the relationships of white matter structural integrity with stroke, major depressive disorder, and Alzheimer disease. This genome-wide association analysis included 8448 individuals from UK Biobank-a population-based cohort study that recruited individuals from across the United Kingdom between 2006 and 2010, aged 40 to 69 years. Microstructural integrity was measured as fractional anisotropy- (FA) and mean diffusivity (MD)-derived parameters on diffusion tensor images. White matter hyperintensity volumes (WMHV) were assessed on T2-weighted fluid-attenuated inversion recovery images. We identified 1 novel locus at genome-wide significance ( VCAN [versican]: rs13164785; P =3.7×10 -18 for MD and rs67827860; P =1.3×10 -14 for FA). LD score regression showed a significant genome-wide correlation between FA, MD, and WMHV (FA-WMHV rG 0.39 [SE, 0.15]; MD-WMHV rG 0.56 [SE, 0.19]). In polygenic risk score analysis, FA, MD, and WMHV were significantly associated with lacunar stroke, MD with major depressive disorder, and WMHV with Alzheimer disease. Genetic variants within the VCAN gene may play a role in the mechanisms underlying microstructural integrity of the white matter in the brain measured as FA and MD. Mechanisms underlying white matter alterations are shared with cerebrovascular disease, and inherited differences in white matter microstructure impact on Alzheimer disease and major depressive disorder. © 2018 The Authors.

Molecular pathogenesis and clinical management of Fanconi anemia

PubMed Central

Kee, Younghoon; D’Andrea, Alan D.

2012-01-01

Fanconi anemia (FA) is a rare genetic disorder associated with a high frequency of hematological abnormalities and congenital anomalies. Based on multilateral efforts from basic scientists and clinicians, significant advances in our knowledge of FA have been made in recent years. Here we review the clinical features, the diagnostic criteria, and the current and future therapies of FA and describe the current understanding of the molecular basis of the disease. PMID:23114602

Insights into Fanconi Anaemia from the structure of human FANCE

PubMed Central

Nookala, Ravi K.; Hussain, Shobbir; Pellegrini, Luca

2007-01-01

Fanconi Anaemia (FA) is a cancer predisposition disorder characterized by spontaneous chromosome breakage and high cellular sensitivity to genotoxic agents. In response to DNA damage, a multi-subunit assembly of FA proteins, the FA core complex, monoubiquitinates the downstream FANCD2 protein. The FANCE protein plays an essential role in the FA process of DNA repair as the FANCD2-binding component of the FA core complex. Here we report a crystallographic and biological study of human FANCE. The first structure of a FA protein reveals the presence of a repeated helical motif that provides a template for the structural rationalization of other proteins defective in Fanconi Anaemia. The portion of FANCE defined by our crystallographic analysis is sufficient for interaction with FANCD2, yielding structural information into the mode of FANCD2 recruitment to the FA core complex. Disease-associated mutations disrupt the FANCE–FANCD2 interaction, providing structural insight into the molecular mechanisms of FA pathogenesis. PMID:17308347

A systems biology approach for elucidating the interaction of curcumin with Fanconi anemia FANC G protein and the key disease targets of leukemia.

PubMed

Mahato, David; Samanta, Dipayan; Mukhopadhyay, Sudit S; Krishnaraj, R Navanietha

2017-06-01

Fanconi anemia (FA) is an autosomal recessive disorder with a high risk of malignancies including acute myeloid leukemia and squamous cell carcinoma. There is a constant search out of new potential therapeutic molecule to combat this disorder. In most cases, patients with FA develop haematological malignancies with acute myeloid leukemia and acute lymphoblastic leukemia. Identifying drugs which can efficiently block the pathways of both these disorders can be an ideal and novel strategy to treat FA. The curcumin, a natural compound obtained from turmeric is an interesting therapeutic molecule as it has been reported in the literature to combat both FA as well as leukemia. However, its complete mechanism is not elucidated. Herein, a systems biology approach for elucidating the therapeutic potential of curcumin against FA and leukemia is investigated by analyzing the computational molecular interactions of curcumin ligand with FANC G of FA and seven other key disease targets of leukemia. The proteins namely DOT1L, farnesyl transferase (FDPS), histone decetylase (EP3000), Polo-like kinase (PLK-2), aurora-like kinase (AUKRB), tyrosine kinase (ABL1), and retinoic acid receptor alpha (RARA) were chosen as disease targets for leukemia and modeled structure of FANC G protein as the disease target for FA. The docking investigations showed that curcumin had a very high binding affinity of -8.1 kcal/mol with FANC G protein. The key disease targets of leukemia namely tyrosine kinase (ABL1), aurora-like kinase (AUKRB), and polo-like kinase (PLK-2) showed that they had the comparable binding affinities of -9.7 k cal/mol, -8.7 k cal/mol, and -8.6 k cal/mol, respectively with curcumin. Further, the percentage similarity scores obtained from PAM50 using EMBOSS MATCHER was shown to provide a clue to understand the structural relationships to an extent and to predict the binding affinity. This investigation shows that curcumin effectively interacts with the disease targets of both FA and leukemia.

Sorption of Eu(III) on humic acid or fulvic acid bound to hydrous alumina studied by SEM-EDS, XPS, TRLFS, and batch techniques.

PubMed

Tan, X L; Wang, X K; Geckeis, H; Rabung, Th

2008-09-01

To identify the effect of humic acid (HA) and fulvic acid (FA) on the sorption mechanism of Eu(III) on organic--inorganic colloids in the environment at a molecular level, surface adsorbed/ complexed Eu(III) on hydrous alumina, HA-, and FA-hydrous alumina hybrids were characterized by using X-ray photoelectron spectroscopy (XPS) and time-resolved laser fluorescence spectroscopy (TRLFS). The experiments were performed in 0.1 mol/L KNO3 or 0.1 mol/L NaClO4 under ambient conditions. The pH values were varied between 2 and 11 at a fixed Eu(III) concentration of 6.0 x 10(-7) mol/L and 4.3 x 10(-5) mol/L. The different Eu(III)/FA(HA)/hydrous alumina complexes were characterized by their fluorescence emission spectra ((5D0-F1)/ (5D0 --> 7F2)) and binding energy of Eu(III). Inner-sphere surface complexation may contribute mainly to Eu(III) sorption on hydrous alumina, and a ternary surface complex is formed at the HA/ FA-hydrous alumina hybrid surfaces. The sorption and species of Eu(III) in ternary Eu-HA/FA-hydrous alumina systems are not dominated by either HA/FA or hydrous alumina, but are dominated by both HA/FA and hydrous alumina. The results are important for understanding the sorption mechanisms and the nature of surface adsorbed Eu(III) species and trivalent chemical homologues of Eu(III) in the natural environment.

Stem Cell Genetic Therapy for Fanconi Anemia - A New Hope.

PubMed

Hanenberg, Helmut; Roellecke, Katharina; Wiek, Constanze

2017-01-01

Fanconi anemia (FA) is a rare inherited DNA disorder clinically characterized by congenital malformations, progressive bone marrow failure, and cancer susceptibility. Due to a strong survival advantage of spontaneously corrected 'normal' hematopoietic stem cells (HSCs) in a few patients, FA is considered a model disorder for genetic correction of autologous stem cells, where genetically corrected stem cells and their progeny have a strong in vivo selective advantage, ultimately leading to normal hematopoiesis. Despite these apparently ideal circumstances, three HSC gene therapy trials with gammaretroviral vectors (stage I) designed to cure the hematological manifestation of FA completely failed to provide long-term clinical benefits for patients, predominantly due to the combination of insufficient gene transfer technologies and incompletely understood FA HSC pathobiology. Currently, FA gene therapy is in stage II where, based on an improved understanding of the cellular defects in FA HSCs, consequently adapted transduction protocols are being used in two phase I/II trials for in vitro genetic correction of FANCA-deficient hematopoietic stem cells. These results are eagerly awaited. Independent from the outcome of these studies, technologies are already available that seem highly attractive for testing in FA. In stage III, this would ultimately include targeted in vivo correction of autologous HSCs by overexpression of nonintegrating lentiviral vectors with scaffold/matrix attachment region elements using specific envelopes as pseudotypes. Although currently still challenging, in a few years in vivo genome editing approaches will be readily available in stage IV, in which the delivery of the editing machinery/ complex is targeted to the autologous FA HSCs by the nonintegrating lentiviral vectors established in stage III. Even low levels of corrected stem cells will then quickly repopulate the entire hematopoiesis of the patient. We therefore are sanguine that in the future, genetic therapy can be used clinically for the correction of FA HSCs in the standard care of FA patients. Copyright© Bentham Science Publishers; For any queries, please email at epub@benthamscience.org.

Metformin improves defective hematopoiesis and delays tumor formation in Fanconi anemia mice.

PubMed

Zhang, Qing-Shuo; Tang, Weiliang; Deater, Matthew; Phan, Ngoc; Marcogliese, Andrea N; Li, Hui; Al-Dhalimy, Muhsen; Major, Angela; Olson, Susan; Monnat, Raymond J; Grompe, Markus

2016-12-15

Fanconi anemia (FA) is an inherited bone marrow failure disorder associated with a high incidence of leukemia and solid tumors. Bone marrow transplantation is currently the only curative therapy for the hematopoietic complications of this disorder. However, long-term morbidity and mortality remain very high, and new therapeutics are badly needed. Here we show that the widely used diabetes drug metformin improves hematopoiesis and delays tumor formation in Fancd2 -/- mice. Metformin is the first compound reported to improve both of these FA phenotypes. Importantly, the beneficial effects are specific to FA mice and are not seen in the wild-type controls. In this preclinical model of FA, metformin outperformed the current standard of care, oxymetholone, by improving peripheral blood counts in Fancd2 -/- mice significantly faster. Metformin increased the size of the hematopoietic stem cell compartment and enhanced quiescence in hematopoietic stem and progenitor cells. In tumor-prone Fancd2 -/- Trp53 +/- mice, metformin delayed the onset of tumors and significantly extended the tumor-free survival time. In addition, we found that metformin and the structurally related compound aminoguanidine reduced DNA damage and ameliorated spontaneous chromosome breakage and radials in human FA patient-derived cells. Our results also indicate that aldehyde detoxification might be one of the mechanisms by which metformin reduces DNA damage in FA cells. © 2016 by The American Society of Hematology.

Fanconi Anemia complementation group C protein in metabolic disorders.

PubMed

Nepal, Manoj; Ma, Chi; Xie, Guoxiang; Jia, Wei; Fei, Peiwen

2018-06-21

Given importance of 22-Fanconi Anemia (FA) proteins together to act in a signaling pathway in preventing deleterious clinical symptoms, e.g. severe bone marrow failure, congenital defects, an early onset of aging and cancer, studies on each FA protein become increasingly attractive. However, an unbiased and systematic investigation of cellular effects resulting from each FA protein is missing. Here, we report roles of FA complementation C group protein (FANCC) in the protection from metabolic disorders. This study was prompted by the diabetes-prone feature displayed in FANCC knockout mice, which is not typically shown in patients with FA. We found that in cells expressing FANCC at different levels, there are representative alterations in metabolites associated with aging (glycine, citrulline, ornithine, L-asparagine, L-tyrosine, L-arginine, L-glutamine, L-leucine, L-isoleucine, L-valine, L-proline and L-alanine), Diabetes Mellitus (DM) (carbon monoxide, collagens, fatty acids, D-glucose, fumaric acid, 2-oxoglutaric acid, C3), inflammation (inosine, L-arginine, L-isoleucine, L-leucine, L-lysine, L-phenylalanine, hypoxanthine, L-methionine), and cancer ( L-methionine, sphingomyelin, acetyl-L-carnitine, L-aspartic acid, L-glutamic acid, niacinamide, phospho-rylethanolamine). We also found that FANCC can act in an FA-pathway-independent manner in tumor suppression. Collectively, featured-metabolic alterations are readouts of functional mechanisms underlying reduced tumorigenicity driven by FANCC, demonstrating close links among cancer, aging, inflammation and DM.

Emulsified omega-3 fatty-acids modulate the symptoms of depressive disorder in children and adolescents: a pilot study.

PubMed

Trebatická, Jana; Hradečná, Zuzana; Böhmer, František; Vaváková, Magdaléna; Waczulíková, Iveta; Garaiova, Iveta; Luha, Ján; Škodáček, Igor; Šuba, Ján; Ďuračková, Zdeňka

2017-01-01

The prevalence of mood disorders in children is a growing global concern. Omega-3 fatty acids (FA) are emerging as a promising adjuvant therapy for depressive disorder (DD) in paediatric patients. The primary objective of this pilot, single-centre, randomized, double-blind controlled study was to compare the efficacy of an Omega-3 FA fish oil emulsion with a control oil emulsion alongside standard treatment for depressive symptoms in children and adolescents suffering from depressive disorder (DD) and mixed anxiety depressive disorder (MADD). 38 children (12 patients were treated and diagnosed for at least 1 month before enrolment, 26 patients were first-time diagnosed as DD) aged 11-17 years were randomised 1:1 to the intervention (Omega-3 FA, 19 patients) or active comparator (Omega-6 FA, 19 patients) groups. Children's depression inventory (CDI) ratings were performed at baseline, every 2 weeks for a 12-week intervention period and at 4-week post-intervention. 35 patients (17 in Omega-3 and 18 in Omega-6 groups) who completed the whole intervention period were evaluated. Patients from Omega-3 group were stratified according to diagnosis into two subgroups (DD-10/17 and mixed anxiety depressive disorder (MADD)-7/17 patients) and in the Omega-6 group into DD-10/18 and MADD-8/18 patients. Groups were evaluated separately. Differences between-groups were tested with the Student´s t test or non-parametric Mann-Whitney U test. Two-way ANOVA with repeated measures and Friedman test were used to analyse the Treatment effect for response in CDI score. p < 0.05 was considered significant in all statistical analyses. Significant reductions in CDI scores in 35 analysed patients who completed 12 weeks intervention were observed after 12 weeks of intervention only in the Omega-3 group (p = 0.034). After stratification to depressive disorder and mixed anxiety depressive disorder subgroups, the DD subgroup receiving the Omega-3 FA fish oil showed statistically greater improvement (score reduction after 8 week treatment of -9.1 CDI, p = 0.0001) when compared to the MADD subgroup (score reduction after 8 week treatment -4.24 CDI, p = 0.271). CDI scores were reduced in the Omega-3 group and the depression subgroup had greater improvement than the mixed depressive/anxiety group. An Omega-3 fatty acid rich fish oil emulsion may be an effective adjuvant supplement during the treatment of depressive disorders in children. Trial registration ISRCTN81655012.

Marine omega-3 fatty acids and mood disorders--linking the sea and the soul. 'Food for Thought' I.

PubMed

Hegarty, B D; Parker, G B

2011-07-01

While there has long been interest in any nutritional contribution to the onset and treatment of mood disorders, there has been increasing scientific evaluation of several candidate nutritional and dietary factors in recent years. In this inaugural study of our 'Food for Thought' series, we will overview the evidence for any role of omega-3 fatty acids (FA) in regulating mood. Relevant literature was identified through online database searches and cross-referencing. Plausible mechanisms exist by which omega-3 FA may influence neuronal function and mood. Cross-sectional studies demonstrate an association between omega-3 fatty acid deficiency and both depressive and bipolar disorders. Studies investigating the efficacy of omega-3 fatty acid supplementation for mood disorders have however provided inconsistent results. The proportion of treatment studies showing a significant advantage of omega-3 supplementation has dropped over the last 5 years. However, the vast heterogeneity of the trials in terms of constituent omega-3 FAs, dose and length of treatment makes comparisons of these studies difficult. More research is required before omega-3 supplementation can be firmly recommended as an effective treatment for mood disorders. Whereas increased omega-3 FA intake may alleviate depressive symptoms, there is little evidence of any benefit for mania. © 2011 John Wiley & Sons A/S.

Serum Levels of Fetal Antigen 1 in Extreme Nutritional States

PubMed Central

Andries, Alin; Niemeier, Andreas; Støving, Rene K.; Abdallah, Basem M.; Wolf, Anna-Maria; Hørder, Kirsten; Kassem, Moustapha

2012-01-01

Objective. Recent data suggest that fetal antigen (FA1) is linked to disorders of body weight. Thus, we measured FA1 serum levels in two extreme nutritional states of morbid obesity (MO) and anorexia nervosa (AN) and monitored its response to weight changes. Design. FA1 and insulin serum concentrations were assessed in a cross-sectional study design at defined time points after gastric restrictive surgery for 25 MO patients and 15 women with AN. Results. Absolute FA1 serum levels were within the assay normal range and were not different between the groups at baseline. However, the ratio of FA1/BMI was significantly higher in AN. FA1 was inversely correlated with BMI before and after weight change in AN, but not in MO patients. In addition, MO patients displayed a significant concomitant decrease of FA1 and insulin with the first 25% of EWL, while in AN patients a significant increase of FA1 was observed in association with weight gain. Conclusion. FA1 is a sensitive indicator of metabolic adaptation during weight change. While FA1 serum levels in humans generally do not correlate with BMI, our results suggest that changes in FA1 serum levels reflect changes in adipose tissue turnover. PMID:22844611

Superparamagnetic poly(methyl methacrylate) nanoparticles surface modified with folic acid presenting cell uptake mediated by endocytosis

NASA Astrophysics Data System (ADS)

Feuser, Paulo Emilio; Jacques, Amanda Virtuoso; Arévalo, Juan Marcelo Carpio; Rocha, Maria Eliane Merlin; dos Santos-Silva, Maria Claudia; Sayer, Claudia; de Araújo, Pedro H. Hermes

2016-04-01

The encapsulation of superparamagnetic nanoparticles (MNPs) in polymeric nanoparticles (NPs) with modified surfaces can improve targeted delivery and induce cell death by hyperthermia. The goals of this study were to synthesize and characterize surface modified superparamagnetic poly(methyl methacrylate) with folic acid (FA) prepared by miniemulsion polymerization (MNPsPMMA-FA) and to evaluate their in vitro cytotoxicity and cellular uptake in non-tumor cells, murine fibroblast (L929) cells and tumor cells that overexpressed folate receptor (FR) β, and chronic myeloid leukemia cells in blast crisis (K562). Lastly, hemolysis assays were performed on human red blood cells. MNPsPMMA-FA presented an average mean diameter of 135 nm and a saturation magnetization (Ms) value of 37 emu/g of iron oxide, as well as superparamagnetic behavior. The MNPsPMMA-FA did not present cytotoxicity in L929 and K562 cells. Cellular uptake assays showed a higher uptake of MNPsPMMA-FA than MNPsPMMA in K562 cells when incubated at 37 °C. On the other hand, MNPsPMMA-FA showed a low uptake when endocytosis mechanisms were blocked at low temperature (4 °C), suggesting that the MNPsPMMA-FA uptake was mediated by endocytosis. High concentrations of MNPsPMMA-FA showed hemocompatibility when incubated for 24 h in human red blood cells. Therefore, our results suggest that these carrier systems can be an excellent alternative in targeted drug delivery via FR.

Paternal or Maternal Uniparental Disomy of Chromosome 16 Resulting in Homozygosity of a Mutant Allele Causes Fanconi Anemia.

PubMed

Donovan, Frank X; Kimble, Danielle C; Kim, Yonghwan; Lach, Francis P; Harper, Ursula; Kamat, Aparna; Jones, MaryPat; Sanborn, Erica M; Tryon, Rebecca; Wagner, John E; MacMillan, Margaret L; Ostrander, Elaine A; Auerbach, Arleen D; Smogorzewska, Agata; Chandrasekharappa, Settara C

2016-05-01

Fanconi anemia (FA) is a rare inherited disorder caused by pathogenic variants in one of 19 FANC genes. FA patients display congenital abnormalities, and develop bone marrow failure, and cancer susceptibility. We identified homozygous mutations in four FA patients and, in each case, only one parent carried the obligate mutant allele. FANCA and FANCP/SLX4 genes, both located on chromosome 16, were the affected recessive FA genes in three and one family respectively. Genotyping with short tandem repeat markers and SNP arrays revealed uniparental disomy (UPD) of the entire mutation-carrying chromosome 16 in all four patients. One FANCA patient had paternal UPD, whereas FA in the other three patients resulted from maternal UPD. These are the first reported cases of UPD as a cause of FA. UPD indicates a reduced risk of having another child with FA in the family and has implications in prenatal diagnosis. © 2016 WILEY PERIODICALS, INC.

Modeling Fanconi Anemia pathogenesis and therapeutics using integration-free patient-derived iPSCs

PubMed Central

Montserrat, Nuria; Tarantino, Carolina; Gu, Ying; Yi, Fei; Xu, Xiuling; Zhang, Weiqi; Ruiz, Sergio; Plongthongkum, Nongluk; Zhang, Kun; Masuda, Shigeo; Nivet, Emmanuel; Tsunekawa, Yuji; Soligalla, Rupa Devi; Goebl, April; Aizawa, Emi; Kim, Na Young; Kim, Jessica; Dubova, Ilir; Li, Ying; Ren, Ruotong; Benner, Chris; del Sol, Antonio; Bueren, Juan; Trujillo, Juan Pablo; Surralles, Jordi; Cappelli, Enrico; Dufour, Carlo; Esteban, Concepcion Rodriguez; Belmonte, Juan Carlos Izpisua

2014-01-01

Fanconi Anemia (FA) is a recessive disorder characterized by genomic instability, congenital abnormalities, cancer predisposition and bone marrow failure. However, the pathogenesis of FA is not fully understood partly due to the limitations of current disease models. Here, we derive integration-free induced pluripotent stem cells (iPSCs) from an FA patient without genetic complementation and report in situ gene correction in FA-iPSCs as well as the generation of isogenic FANCA deficient human embryonic stem cell (ESC) lines. FA cellular phenotypes are recapitulated in iPSCs/ESCs and their adult stem/progenitor cell derivatives. By using isogenic pathogenic mutation-free controls as well as cellular and genomic tools, our model serves to facilitate the discovery of novel disease features. We validate our model as a drug-screening platform by identifying several compounds that improve hematopoietic differentiation of FA-iPSCs. These compounds are also able to rescue the hematopoietic phenotype of FA-patient bone marrow cells. PMID:24999918

Knockdown of Fanconi anemia genes in human embryonic stem cells reveals early developmental defects in the hematopoietic lineage.

PubMed

Tulpule, Asmin; Lensch, M William; Miller, Justine D; Austin, Karyn; D'Andrea, Alan; Schlaeger, Thorsten M; Shimamura, Akiko; Daley, George Q

2010-04-29

Fanconi anemia (FA) is a genetically heterogeneous, autosomal recessive disorder characterized by pediatric bone marrow failure and congenital anomalies. The effect of FA gene deficiency on hematopoietic development in utero remains poorly described as mouse models of FA do not develop hematopoietic failure and such studies cannot be performed on patients. We have created a human-specific in vitro system to study early hematopoietic development in FA using a lentiviral RNA interference (RNAi) strategy in human embryonic stem cells (hESCs). We show that knockdown of FANCA and FANCD2 in hESCs leads to a reduction in hematopoietic fates and progenitor numbers that can be rescued by FA gene complementation. Our data indicate that hematopoiesis is impaired in FA from the earliest stages of development, suggesting that deficiencies in embryonic hematopoiesis may underlie the progression to bone marrow failure in FA. This work illustrates how hESCs can provide unique insights into human development and further our understanding of genetic disease.

Alpha-fetoprotein and Fanconi Anemia: Relevance to DNA Repair and Breast Cancer Susceptibility.

PubMed

Lakhi, Nisha A; Mizejewski, Gerald J

2017-02-01

Elevations of serum alpha-fetoprotein (sAFP) have been reported in fetal and infant states of anemia. Fanconi anemia (FA) belongs to a family of genetic instability disorders which lack the capability to repair DNA breaks. The lesion occurs at a checkpoint regulatory step of the G2 to mitotic transition, allowing FA cells to override cell-cycle arrest. FA DNA repair pathways contain complementation groups known as FANC proteins. FANC proteins form multi-protein complexes with BRCA proteins and are involved in homologous DNA repair. An impaired cascade in these events imparts an increased breast cancer susceptibility to female FA patients. Elevations of sAFP have availed this fetal protein to serve as a biomarker for FA disease. However, the origin of the synthesis of sAFA has not been determined in FA patients. We hypothesize that hematopoietic multipotent progenitor stem cells in the bone marrow are the source of sAFP production in FA patients.

Modelling Fanconi anemia pathogenesis and therapeutics using integration-free patient-derived iPSCs.

PubMed

Liu, Guang-Hui; Suzuki, Keiichiro; Li, Mo; Qu, Jing; Montserrat, Nuria; Tarantino, Carolina; Gu, Ying; Yi, Fei; Xu, Xiuling; Zhang, Weiqi; Ruiz, Sergio; Plongthongkum, Nongluk; Zhang, Kun; Masuda, Shigeo; Nivet, Emmanuel; Tsunekawa, Yuji; Soligalla, Rupa Devi; Goebl, April; Aizawa, Emi; Kim, Na Young; Kim, Jessica; Dubova, Ilir; Li, Ying; Ren, Ruotong; Benner, Chris; Del Sol, Antonio; Bueren, Juan; Trujillo, Juan Pablo; Surralles, Jordi; Cappelli, Enrico; Dufour, Carlo; Esteban, Concepcion Rodriguez; Belmonte, Juan Carlos Izpisua

2014-07-07

Fanconi anaemia (FA) is a recessive disorder characterized by genomic instability, congenital abnormalities, cancer predisposition and bone marrow (BM) failure. However, the pathogenesis of FA is not fully understood partly due to the limitations of current disease models. Here, we derive integration free-induced pluripotent stem cells (iPSCs) from an FA patient without genetic complementation and report in situ gene correction in FA-iPSCs as well as the generation of isogenic FANCA-deficient human embryonic stem cell (ESC) lines. FA cellular phenotypes are recapitulated in iPSCs/ESCs and their adult stem/progenitor cell derivatives. By using isogenic pathogenic mutation-free controls as well as cellular and genomic tools, our model serves to facilitate the discovery of novel disease features. We validate our model as a drug-screening platform by identifying several compounds that improve hematopoietic differentiation of FA-iPSCs. These compounds are also able to rescue the hematopoietic phenotype of FA patient BM cells.

Paternal or maternal uniparental disomy of chromosome 16 resulting in homozygosity of a mutant allele causes Fanconi anemia

PubMed Central

Donovan, Frank X.; Kimble, Danielle C.; Kim, Yonghwan; Lach, Francis P.; Harper, Ursula; Kamat, Aparna; Jones, MaryPat; Sanborn, Erica M.; Tryon, Rebecca; Wagner, John E.; MacMillan, Margaret L.; Ostrander, Elaine A.; Auerbach, Arleen D.; Smogorzewska, Agata; Chandrasekharappa, Settara C.

2016-01-01

Fanconi anemia (FA) is a rare inherited disorder caused by pathogenic variants in one of 19 FANC genes. FA patients display congenital abnormalities, and develop bone marrow failure, and cancer susceptibility. We identified homozygous mutations in four FA patients and, in each case, only one parent carried the obligate mutant allele. FANCA and FANCP/SLX4 genes, both located on chromosome 16, were the affected recessive FA genes in three and one family respectively. Genotyping with short tandem repeat markers and single nucleotide polymorphism (SNP) arrays revealed uniparental disomy (UPD) of the entire mutation-carrying chromosome 16 in all four patients. One FANCA patient had paternal UPD, whereas FA in the other three patients resulted from maternal UPD. These are the first reported cases of UPD as a cause of FA. UPD indicates a reduced risk of having another child with FA in the family and has implications in prenatal diagnosis. PMID:26841305

Analysis of the "endocannabinoidome" in peripheral tissues of obese Zucker rats.

PubMed

Iannotti, F A; Piscitelli, F; Martella, A; Mazzarella, E; Allarà, M; Palmieri, V; Parrella, C; Capasso, R; Di Marzo, V

2013-08-01

The endocannabinoid system (ECS) represents one of the major determinants of metabolic disorders. We investigated potential changes in the endogenous levels of anandamide (AEA), 2-arachidonoylglycerol (2-AG), N-oleoylethanolamine (OEA) and N-palmitoylethanolamine (PEA) in some peripheral organs and tissues of obese Zucker(fa/fa) and lean Zucker(fa/+) rats by qPCR, liquid chromatography mass spectrometry, western blot and enzymatic activity assays. At 10-12 weeks of age AEA levels were significantly lower in BAT, small intestine and heart and higher in soleus of Zucker(fa/fa) rats. In this tissue, also the expression of CB1 receptors was higher. By contrast in Zucker(fa/fa) rats, 2-AG levels were changed (and lower) solely in the small and large intestine. Finally, in Zucker(fa/fa), PEA levels were unchanged, whereas OEA was slightly lower in BAT, and higher in the large intestine. Interestingly, these differences were accompanied by differential alterations of the genes regulating ECS tone. In conclusion, the levels of endocannabinoids are altered during obesity in a way partly correlating with changes of the genes related to their metabolism and activity. Copyright © 2013 Elsevier Ltd. All rights reserved.

Comparison of the internalization of targeted dendrimers and dendrimer-entrapped gold nanoparticles into cancer cells.

PubMed

Shi, Xiangyang; Wang, Su He; Lee, Inhan; Shen, Mingwu; Baker, James R

2009-11-01

Dendrimer-based nanotechnology significantly advances the area of targeted cancer imaging and therapy. Herein, we compared the difference of surface acetylated fluorescein isocyanate (FI) and folic acid (FA) modified generation 5 (G5) poly(amidoamine) dendrimers (G5.NHAc-FI-FA), and dendrimer-entrapped gold nanoparticles with similar modifications ([(Au(0))(51.2)-G5.NHAc-FI-FA]) in terms of their specific internalization to FA receptor (FAR)-overexpressing cancer cells. Confocal microscopic studies show that both G5.NHAc-FI-FA and [(Au(0))(51.2-)G5.NHAc-FI-FA] exhibit similar internalization kinetics regardless of the existence of Au nanoparticles (NPs). Molecular dynamics simulation of the two different nanostructures reveals that the surface area and the FA moiety distribution from the center of the geometry are slightly different. This slight difference may not be recognized by the FARs on the cell membrane, consequently leading to similar internalization kinetics. This study underlines the fact that metal or inorganic NPs entrapped within dendrimers interact with cells in a similar way to that of dendrimers lacking host NPs. 2009 Wiley Periodicals, Inc.

Exonuclease III-assisted graphene oxide amplified fluorescence anisotropy strategy for ricin detection.

PubMed

Xiao, Xue; Tao, Jing; Zhang, Hong Zhi; Huang, Cheng Zhi; Zhen, Shu Jun

2016-11-15

Graphene oxide (GO) is an excellent fluorescence anisotropy (FA) amplifier. However, in the conventional GO amplified FA strategy, one target can only induce the FA change of one fluorophore on probe, which limits the detection sensitivity. Herein, we developed an exonuclease III (Exo III) aided GO amplified FA strategy by using aptamer as an recognition element and ricin B-chain as a proof-of-concept target. The aptamer was hybridized with a blocker sequence and linked onto the surface of magnetic beads (MBs). Upon the addition of ricin B-chain, blocker was released from the surface of MBs and hybridized with the dye-modified probe DNA on the surface of GO through the toehold-mediated strand exchange reaction. The formed blocker-probe DNA duplex triggered the Exo III-assisted cyclic signal amplification by repeating the hybridization and digestion of probe DNA, liberating the fluorophore with several nucleotides (low FA value). Thus, ricin B-chain could be sensitively detected by the significantly decreased FA. The linear range was from 1.0μg/mL to 13.3μg/mL and the limit of detection (LOD) was 400ng/mL. This method improved the sensitivity of FA assay and it could be generalized to any kind of target detection based on the use of an appropriate aptamer. Copyright © 2016 Elsevier B.V. All rights reserved.

Relationship between symptom dimensions and white matter alterations in obsessive-compulsive disorder.

PubMed

Yagi, Michiyo; Hirano, Yoshiyuki; Nakazato, Michiko; Nemoto, Kiyotaka; Ishikawa, Kazuhiro; Sutoh, Chihiro; Miyata, Haruko; Matsumoto, Junko; Matsumoto, Koji; Masuda, Yoshitada; Obata, Takayuki; Iyo, Masaomi; Shimizu, Eiji; Nakagawa, Akiko

2017-06-01

To investigate the relationship between the severities of symptom dimensions in obsessive-compulsive disorder (OCD) and white matter alterations. We applied tract-based spatial statistics for diffusion tensor imaging (DTI) acquired by 3T magnetic resonance imaging. First, we compared fractional anisotropy (FA) between 20 OCD patients and 30 healthy controls (HC). Then, applying whole brain analysis, we searched the brain regions showing correlations between the severities of symptom dimensions assessed by Obsessive-Compulsive Inventory-Revised and FA in all participants. Finally, we calculated the correlations between the six symptom dimensions and multiple DTI measures [FA, axial diffusivity (AD), radial diffusivity (RD), mean diffusivity (MD)] in a region-of-interest (ROI) analysis and explored the differences between OCD patients and HC. There were no between-group differences in FA or brain region correlations between the severities of symptom dimensions and FA in any of the participants. ROI analysis revealed negative correlations between checking severity and left inferior frontal gyrus white matter and left middle temporal gyrus white matter and a positive correlation between ordering severity and right precuneus in FA in OCD compared with HC. We also found negative correlations between ordering severity and right precuneus in RD, between obsessing severities and right supramarginal gyrus in AD and MD, and between hoarding severity and right insular gyrus in AD. Our study supported the hypothesis that the severities of respective symptom dimensions are associated with different patterns of white matter alterations.

Lipid Processing in the Brain: A Key Regulator of Systemic Metabolism

PubMed Central

Bruce, Kimberley D.; Zsombok, Andrea; Eckel, Robert H.

2017-01-01

Metabolic disorders, particularly aberrations in lipid homeostasis, such as obesity, type 2 diabetes mellitus, and hypertriglyceridemia often manifest together as the metabolic syndrome (MetS). Despite major advances in our understanding of the pathogenesis of these disorders, the prevalence of the MetS continues to rise. It is becoming increasingly apparent that intermediary metabolism within the central nervous system is a major contributor to the regulation of systemic metabolism. In particular, lipid metabolism within the brain is tightly regulated to maintain neuronal structure and function and may signal nutrient status to modulate metabolism in key peripheral tissues such as the liver. There is now a growing body of evidence to suggest that fatty acid (FA) sensing in hypothalamic neurons via accumulation of FAs or FA metabolites may signal nutritional sufficiency and may decrease hepatic glucose production, lipogenesis, and VLDL-TG secretion. In addition, recent studies have highlighted the existence of liver-related neurons that have the potential to direct such signals through parasympathetic and sympathetic nervous system activity. However, to date whether these liver-related neurons are FA sensitive remain to be determined. The findings discussed in this review underscore the importance of the autonomic nervous system in the regulation of systemic metabolism and highlight the need for further research to determine the key features of FA neurons, which may serve as novel therapeutic targets for the treatment of metabolic disorders. PMID:28421037

Investigation of aluminum gate CMP in a novel alkaline solution

NASA Astrophysics Data System (ADS)

Cuiyue, Feng; Yuling, Liu; Ming, Sun; Wenqian, Zhang; Jin, Zhang; Shuai, Wang

2016-01-01

Beyond 45 nm, due to the superior CMP performance requirements with the metal gate of aluminum in the advanced CMOS process, a novel alkaline slurry for an aluminum gate CMP with poly-amine alkali slurry is investigated. The aluminum gate CMP under alkaline conditions has two steps: stock polishing and fine polishing. A controllable removal rate, the uniformity of aluminum gate and low corrosion are the key challenges for the alkaline polishing slurry of the aluminum gate CMP. This work utilizes the complexation-soluble function of FA/O II and the preference adsorption mechanism of FA/O I nonionic surfactant to improve the uniformity of the surface chemistry function with the electrochemical corrosion research, such as OCP-TIME curves, Tafel curves and AC impedance. The result is that the stock polishing slurry (with SiO2 abrasive) contains 1 wt.% H2O2,0.5 wt.% FA/O II and 1.0 wt.% FA/O I nonionic surfactant. For a fine polishing process, 1.5 wt.% H2O2, 0.4 wt.% FA/O II and 2.0 wt.% FA/O I nonionic surfactant are added. The polishing experiments show that the removal rates are 3000 ± 50 Å/min and 1600 ± 60 Å/min, respectively. The surface roughnesses are 2.05 ± 0.128 nm and 1.59 ± 0.081 nm, respectively. A combination of the functions of FA/O II and FA/O I nonionic surfactant obtains a controllable removal rate and a better surface roughness in alkaline solution.

White matter integrity in Asperger syndrome: a preliminary diffusion tensor magnetic resonance imaging study in adults.

PubMed

Bloemen, Oswald J N; Deeley, Quinton; Sundram, Fred; Daly, Eileen M; Barker, Gareth J; Jones, Derek K; van Amelsvoort, Therese A M J; Schmitz, Nicole; Robertson, Dene; Murphy, Kieran C; Murphy, Declan G M

2010-10-01

Autistic Spectrum Disorder (ASD), including Asperger syndrome and autism, is a highly genetic neurodevelopmental disorder. There is a consensus that ASD has a biological basis, and it has been proposed that it is a "connectivity" disorder. Diffusion Tensor Magnetic Resonance Imaging (DT-MRI) allows measurement of the microstructural integrity of white matter (a proxy measure of "connectivity"). However, nobody has investigated the microstructural integrity of whole brain white matter in people with Asperger syndrome. We measured the fractional anisotropy (FA), mean diffusivity (MD) and radial diffusivity (RD) of white matter, using DT-MRI, in 13 adults with Asperger syndrome and 13 controls. The groups did not differ significantly in overall intelligence and age. FA, MD and RD were assessed using whole brain voxel-based techniques. Adults with Asperger syndrome had a significantly lower FA than controls in 13 clusters. These were largely bilateral and included white matter in the internal capsule, frontal, temporal, parietal and occipital lobes, cingulum and corpus callosum. Adults with Asperger syndrome have widespread significant differences from controls in white matter microstructural integrity.

Pattern of structural brain changes in social anxiety disorder after cognitive behavioral group therapy: a longitudinal multimodal MRI study.

PubMed

Steiger, V R; Brühl, A B; Weidt, S; Delsignore, A; Rufer, M; Jäncke, L; Herwig, U; Hänggi, J

2017-08-01

Social anxiety disorder (SAD) is characterized by fears of social and performance situations. Cognitive behavioral group therapy (CBGT) has in general positive effects on symptoms, distress and avoidance in SAD. Prior studies found increased cortical volumes and decreased fractional anisotropy (FA) in SAD compared with healthy controls (HCs). Thirty-three participants diagnosed with SAD attended in a 10-week CBGT and were scanned before and after therapy. We applied three neuroimaging methods-surface-based morphometry, diffusion tensor imaging and network-based statistics-each with specific longitudinal processing protocols, to investigate CBGT-induced structural brain alterations of the gray and white matter (WM). Surface-based morphometry revealed a significant cortical volume reduction (pre- to post-treatment) in the left inferior parietal cortex, as well as a positive partial correlation between treatment success (indexed by reductions in Liebowitz Social Anxiety Scale) and reductions in cortical volume in bilateral dorsomedial prefrontal cortex. Diffusion tensor imaging analysis revealed a significant increase in FA in bilateral uncinate fasciculus and right inferior longitudinal fasciculus. Network-based statistics revealed a significant increase of structural connectivity in a frontolimbic network. No partial correlations with treatment success have been found in WM analyses. For, we believe, the first time, we present a distinctive pattern of longitudinal structural brain changes after CBGT measured with three established magnetic resonance imaging analyzing techniques. Our findings are in line with previous cross-sectional, unimodal SAD studies and extent them by highlighting anatomical brain alterations that point toward the level of HCs in parallel with a reduction in SAD symptomatology.

Unique white matter microstructural patterns in ADHD presentations-a diffusion tensor imaging study.

PubMed

Svatkova, Alena; Nestrasil, Igor; Rudser, Kyle; Goldenring Fine, Jodene; Bledsoe, Jesse; Semrud-Clikeman, Margaret

2016-09-01

Attention-deficit/hyperactivity disorder predominantly inattentive (ADHD-PI) and combined (ADHD-C) presentations are likely distinct disorders that differ neuroanatomically, neurochemically, and neuropsychologically. However, to date, little is known about specific white matter (WM) regions differentiating ADHD presentations. This study examined differences in WM microstructure using diffusion tensor imaging (DTI) data from 20 ADHD-PI, 18 ADHD-C, and 27 typically developed children. Voxel-wise analysis of DTI measurements in major fiber bundles was carried out using tract-based spatial statistics (TBSS). Clusters showing diffusivity abnormalities were used as regions of interest for regression analysis between fractional anisotropy (FA) and neuropsychological outcomes. Compared to neurotypicals, ADHD-PI children showed higher FA in the anterior thalamic radiations (ATR), bilateral inferior longitudinal fasciculus (ILF), and in the left corticospinal tract (CST). In contrast, the ADHD-C group exhibited higher FA in the bilateral cingulum bundle (CB). In the ADHD-PI group, differences in FA in the left ILF and ATR were accompanied by axial diffusivity (AD) abnormalities. In addition, the ADHD-PI group exhibited atypical mean diffusivity in the forceps minor (FMi) and left ATR and AD differences in right CB compared to healthy subjects. Direct comparison between ADHD presentations demonstrated radial diffusivity differences in FMi. WM clusters with FA irregularities in ADHD were associated with neurobehavioral performance across groups. In conclusion, differences in WM microstructure in ADHD presentations strengthen the theory that ADHD-PI and ADHD-C are two distinct disorders. Regions with WM irregularity seen in both ADHD presentations might serve as predictors of executive and behavioral functioning across groups. Hum Brain Mapp 37:3323-3336, 2016. © 2016 Wiley Periodicals, Inc. © 2016 Wiley Periodicals, Inc.

Combined Prenatal Pesticide Exposure and Folic Acid Intake in Relation to Autism Spectrum Disorder.

PubMed

Schmidt, Rebecca J; Kogan, Vladimir; Shelton, Janie F; Delwiche, Lora; Hansen, Robin L; Ozonoff, Sally; Ma, Claudia C; McCanlies, Erin C; Bennett, Deborah H; Hertz-Picciotto, Irva; Tancredi, Daniel J; Volk, Heather E

2017-09-08

Maternal folic acid (FA) protects against developmental toxicity from certain environmental chemicals. We examined combined exposures to maternal FA and pesticides in relation to autism spectrum disorder (ASD). Participants were California children born from 2000-2007 who were enrolled in the Childhood Autism Risks from Genetics and the Environment (CHARGE) case-control study at age 2-5 y, were clinically confirmed to have ASD (n=296) or typical development (n=220), and had information on maternal supplemental FA and pesticide exposures. Maternal supplemental FA and household pesticide product use were retrospectively collected in telephone interviews from 2003-2011. High vs. low daily FA intake was dichotomized at 800μg (median). Mothers' addresses were linked to a statewide database of commercial applications to estimate agricultural pesticide exposure. High FA intake (≥800μg) during the first pregnancy month and no known pesticide exposure was the reference group for all analyses. Compared with this group, ASD was increased in association with <800μg FA and any indoor pesticide exposure {adjusted odds ratio [OR]=2.5 [95% confidence interval (CI): 1.3, 4.7]} compared with low FA [OR=1.2 (95% CI: 0.7, 2.2)] or indoor pesticides [OR=1.7 (95% CI: 1.1, 2.8)] alone. ORs for the combination of low FA and regular pregnancy exposure (≥6 mo) to pet pesticides or to outdoor sprays and foggers were 3.9 (95% CI: 1.4, 11.5) and 4.1 (95% CI: 1.7, 10.1), respectively. ORs for low maternal FA and agricultural pesticide exposure 3 mo before or after conception were 2.2 (95% CI: 0.7, 6.5) for chlorpyrifos, 2.3 (95% CI: 0.98, 5.3) for organophosphates, 2.1 (95% CI: 0.9, 4.8) for pyrethroids, and 1.5 (95% CI: 0.5, 4.8) for carbamates. Except for carbamates, these ORs were approximately two times greater than those for either exposure alone or for the expected ORs for combined exposures under multiplicative or additive models. In this study population, associations between pesticide exposures and ASD were attenuated among those with high versus low FA intake during the first month of pregnancy. Confirmatory and mechanistic studies are needed. https://doi.org/10.1289/EHP604.

Combined Prenatal Pesticide Exposure and Folic Acid Intake in Relation to Autism Spectrum Disorder

PubMed Central

Kogan, Vladimir; Shelton, Janie F.; Delwiche, Lora; Hansen, Robin L.; Ozonoff, Sally; Ma, Claudia C.; McCanlies, Erin C.; Bennett, Deborah H.; Hertz-Picciotto, Irva; Tancredi, Daniel J.; Volk, Heather E.

2017-01-01

Background: Maternal folic acid (FA) protects against developmental toxicity from certain environmental chemicals. Objective: We examined combined exposures to maternal FA and pesticides in relation to autism spectrum disorder (ASD). Methods: Participants were California children born from 2000–2007 who were enrolled in the Childhood Autism Risks from Genetics and the Environment (CHARGE) case–control study at age 2–5 y, were clinically confirmed to have ASD (n=296) or typical development (n=220), and had information on maternal supplemental FA and pesticide exposures. Maternal supplemental FA and household pesticide product use were retrospectively collected in telephone interviews from 2003–2011. High vs. low daily FA intake was dichotomized at 800μg (median). Mothers’ addresses were linked to a statewide database of commercial applications to estimate agricultural pesticide exposure. Results: High FA intake (≥800μg) during the first pregnancy month and no known pesticide exposure was the reference group for all analyses. Compared with this group, ASD was increased in association with <800μg FA and any indoor pesticide exposure {adjusted odds ratio [OR]=2.5 [95% confidence interval (CI): 1.3, 4.7]} compared with low FA [OR=1.2 (95% CI: 0.7, 2.2)] or indoor pesticides [OR=1.7 (95% CI: 1.1, 2.8)] alone. ORs for the combination of low FA and regular pregnancy exposure (≥6 mo) to pet pesticides or to outdoor sprays and foggers were 3.9 (95% CI: 1.4, 11.5) and 4.1 (95% CI: 1.7, 10.1), respectively. ORs for low maternal FA and agricultural pesticide exposure 3 mo before or after conception were 2.2 (95% CI: 0.7, 6.5) for chlorpyrifos, 2.3 (95% CI: 0.98, 5.3) for organophosphates, 2.1 (95% CI: 0.9, 4.8) for pyrethroids, and 1.5 (95% CI: 0.5, 4.8) for carbamates. Except for carbamates, these ORs were approximately two times greater than those for either exposure alone or for the expected ORs for combined exposures under multiplicative or additive models. Conclusions: In this study population, associations between pesticide exposures and ASD were attenuated among those with high versus low FA intake during the first month of pregnancy. Confirmatory and mechanistic studies are needed. https://doi.org/10.1289/EHP604 PMID:28934093

The influence of water table depth and the free atmospheric state on convective rainfall predisposition

DOE PAGES

Bonetti, Sara; Manoli, Gabriele; Domec, Jean-Christophe; ...

2015-03-16

Here, we report a mechanistic model for the soil-plant system is coupled to a conventional slab representation of the atmospheric boundary layer (ABL) to explore the role of groundwater table (WT) variations and free atmospheric (FA) states on convective rainfall predisposition (CRP) at a Loblolly pine plantation site situated in the lower coastal plain of North Carolina. Predisposition is quantified using the crossing between modeled lifting condensation level (LCL) and convectively grown ABL depth. The LCL-ABL depth crossing is necessary for air saturation but not sufficient for cloud formation and subsequent convective rainfall occurrence. However, such crossing forms the mainmore » template for which all subsequent dynamical processes regulating the formation (or suppression) of convective rainfall operate on. If the feedback between surface fluxes and FA conditions is neglected, a reduction in latent heat flux associated with reduced WT levels is shown to enhance the ABL-LCL crossing probability. When the soil-plant system is fully coupled with ABL dynamics thereby allowing feedback with ABL temperature and humidity, FA states remain the leading control on CRP. However, vegetation water stress plays a role in controlling ABL-LCL crossing when the humidity supply by the FA is within an intermediate range of values. When FA humidity supply is low, cloud formation is suppressed independent of surface latent heat flux. Similarly, when FA moisture supply is high, cloud formation can occur independent of surface latent heat flux. In an intermediate regime of FA moisture supply, the surface latent heat flux controlled by soil water availability can supplement (or suppress) the necessary water vapor leading to reduced LCL and subsequent ABL-LCL crossing. Lastly, it is shown that this intermediate state corresponds to FA values around the mode in observed humidity lapse rates γ w (between -2.5 × 10 -6 and -1.5 × 10 -6 kg kg -1m -1), suggesting that vegetation water uptake may be controlling CRP at the study site.« less

A defined role for multiple Fanconi anemia gene products in DNA-damage-associated ubiquitination.

PubMed

Tan, Winnie; Deans, Andrew J

2017-06-01

Fanconi anemia (FA) is an inherited blood disorder that causes bone marrow failure and high predisposition to cancers. The FA pathway guards the cell's genome stability by orchestrating the repair of interstrand cross-linking during the S phase of the cell cycle, preventing the chromosomal instability that is a key event in bone marrow failure syndrome. Central to the FA pathway is loss of monoubiquitinated forms of the Fanconi proteins FANCI and FANCD2, a process that is normally mediated by a "core complex" of seven other Fanconi proteins. Each protein, when mutated, can cause FA. The FA core-complex-catalyzed reaction is critical for signaling DNA cross-link damage such as that induced by chemotherapies. Here, we present a perspective on the current understanding of FANCI and FANCD2 monoubiquitination-mediated DNA repair. Our recent biochemical reconstitution of the monoubiquitination (and deubiquitination) reactions creates a paradigm for understanding FA. Further biochemical analysis will create new opportunities to address the leukemic phenotype of FA patients. Copyright © 2017 ISEH - International Society for Experimental Hematology. Published by Elsevier Inc. All rights reserved.

Colloidal diatomite, radionickel, and humic substance interaction: a combined batch, XPS, and EXAFS investigation.

PubMed

Sheng, Guodong; Shen, Runpu; Dong, Huaping; Li, Yimin

2013-06-01

This work determined the influence of humic acid (HA) and fulvic acid (FA) on the interaction mechanism and microstructure of Ni(II) onto diatomite by using batch experiments, X-ray photoelectron spectroscopy (XPS), and extended X-ray absorption fine structure (EXAFS) methods. Macroscopic and spectroscopic experiments have been combined to see the evolution of the interaction mechanism and microstructure of Ni(II) in the presence of HA/FA as compared with that in the absence of HA/FA. The results indicated that the interaction of Ni(II) with diatomite presents the expected solution pH edge at 7.0, which is modified by addition of HA/FA. In the presence of HA/FA, the interaction of Ni(II) with diatomite increased below solution pH 7.0, while Ni(II) interaction decreased above solution pH 7.0. XPS analysis suggested that the enrichment of Ni(II) onto diatomite may be due to the formation of (≡SO)2Ni. EXAFS results showed that binary surface complexes and ternary surface complexes of Ni(II) can be simultaneously formed in the presence of HA/FA, whereas only binary surface complexes of Ni(II) are formed in the absence of HA/FA, which contribute to the enhanced Ni(II) uptake at low pH values. The results observed in this work are important for the evaluation of Ni(II) and related radionuclide physicochemical behavior in the natural soil and water environment.

Chemosensitizing tumor cells by targeting the Fanconi anemia pathway with an adenovirus overexpressing dominant-negative FANCA.

PubMed

Ferrer, Miriam; de Winter, Johan P; Mastenbroek, D C Jeroen; Curiel, David T; Gerritsen, Winald R; Giaccone, Giuseppe; Kruyt, Frank A E

2004-08-01

Fanconi anemia (FA) is a rare genetic disorder characterized by bone-marrow failure and cellular hypersensitivity to crosslinking agents, including cisplatin. Here, we studied the use of the FA pathway as a possible target for cancer gene therapy with the aim to sensitize tumor cells for cisplatin by interfering with the FA pathway. As proof-of-principle, FA and non-FA lymphoblast-derived tumors were grown subcutaneously in scid mice and treated with two different concentrations of cisplatin. As predicted, the antitumor response was considerably improved in FA tumors. An adenoviral vector encoding a dominant-negative form of FANCA, FANCA600DN, was generated that interfered with endogenous FANCA-FANCG interaction resulting in the disruption of the FA pathway as illustrated by disturbed FANCD2 monoubiquitination. A panel of cell lines, including non-small-cell lung cancer cells, could be sensitized approximately two- to three-fold for cisplatin after Ad.CMV.FANCA600DN infection that may increase upon enhanced infection efficiency. In conclusion, targeting the FA pathway may provide a novel strategy for the sensitization of solid tumors for cisplatin and, in addition, provides a tool for examining the role of the FA pathway in determining chemoresistance in different tumor types.

FANCM-FAAP24 and FANCJ: FA proteins that metabolize DNA

PubMed Central

Ali, Abdullah Mahmood; Singh, Thiyam Ramsing; Meetei, Amom Ruhikanta

2009-01-01

Fanconi anemia (FA) is a rare autosomal recessive or X-linked disorder characterized by aplastic anemia, cancer susceptibility and cellular sensitivity to DNA crosslinking agents. Eight FA proteins (FANCA, -B, -C, -E, -F, -G, -L and –M) and three non-FA proteins (FAAP100, FAAP24 and HES1) form the FA nuclear core complex that is required for monoubiquitination of the FANCD2-FANCI dimer upon DNA damage. The other three FA proteins, FANCD1/BRCA2, FANCJ/BACH1/BRIP1 and FANCN/PALB2, act in parallel or downstream of the FANCD2-FANCI dimer. Despite the isolation and characterization of several FA proteins, the mechanism by which these proteins protect cells from DNA interstrand crosslinking agents has been unclear. This is because a majority of the FA proteins lack any recognizable functional domains that can provide insight into their function. The recently discovered FANCM (Hef) and FANCJ (BRIP1/BACH1) proteins contain helicase domains, providing potential insight into the role of FA proteins in DNA repair. FANCM with its partner, FAAP24, and FANCJ bind and metabolize a variety of DNA substrates. In this review, we focus on the discovery, structure, and function of the FANCM-FAAP24 and FANCJ proteins. PMID:19379763

Comprehensive characterization of mesenchymal stromal cells from patients with Fanconi anaemia.

PubMed

Mantelli, Melissa; Avanzini, Maria Antonia; Rosti, Vittorio; Ingo, Daniela M; Conforti, Antonella; Novara, Francesca; Arrigo, Giulia; Boni, Marina; Zappatore, Rita; Lenta, Elisa; Moretta, Antonia; Acquafredda, Gloria; de Silvestri, Annalisa; Cirillo, Valentina; Cicchetti, Elisa; Algeri, Mattia; Strocchio, Luisa; Vinti, Luciana; Starc, Nadia; Biagini, Simone; Sirleto, Pietro; Bernasconi, Paolo; Zuffardi, Orsetta; Maserati, Emanuela; Maccario, Rita; Zecca, Marco; Locatelli, Franco; Bernardo, Maria Ester

2015-09-01

Fanconi anaemia (FA) is an inherited disorder characterized by pancytopenia, congenital malformations and a predisposition to develop malignancies. Alterations in the haematopoietic microenvironment of FA patients have been reported, but little is known regarding the components of their bone marrow (BM) stroma. We characterized mesenchymal stromal cells (MSCs) isolated from BM of 18 FA patients both before and after allogeneic haematopoietic stem cell transplantation (HSCT). Morphology, fibroblast colony-forming unit (CFU-F) ability, proliferative capacity, immunophenotype, differentiation potential, ability to support long-term haematopoiesis and immunomodulatory properties of FA-MSCs were analysed and compared with those of MSCs expanded from 15 age-matched healthy donors (HD-MSCs). FA-MSCs were genetically characterized through conventional karyotyping, diepoxybutane-test and array-comparative genomic hybridization. FA-MSCs generated before and after HSCT were compared. Morphology, immunophenotype, differentiation potential, ability in vitro to inhibit mitogen-induced T-cell proliferation and to support long-term haematopoiesis did not differ between FA-MSCs and HD-MSCs. CFU-F ability and proliferative capacity of FA-MSCs isolated after HSCT were significantly lower than those of HD-MSCs. FA-MSCs reached senescence significantly earlier than HD-MSCs and showed spontaneous chromosome fragility. Our findings indicate that FA-MSCs are defective in their ability to survive in vitro and display spontaneous chromosome breakages; whether these defects are involved in pathophysiology of BM failure syndromes deserves further investigation. © 2015 John Wiley & Sons Ltd.

Novel homozygous FANCL mutation and somatic heterozygous SETBP1 mutation in a Chinese girl with Fanconi Anemia.

PubMed

Wu, Weiqing; Liu, Yang; Zhou, Qinghua; Wang, Qin; Luo, Fuwei; Xu, Zhiyong; Geng, Qian; Li, Peining; Zhang, Hui Z; Xie, Jiansheng

2017-07-01

Fanconi Anemia (FA) is a rare genetically heterogeneous disorder with 17 known complement groups caused by mutations in different genes. FA complementation group L (FA-L, OMIM #608111) occurred in 0.2% of all FA and only eight mutant variants in the FANCL gene were documented. Phenotype and genotype correlation in FANCL associated FA is still obscure. Here we describe a Chinese girl with FA-L caused by a novel homozygous mutation c.822_823insCTTTCAGG (p.Asp275LeufsX13) in the FANCL gene. The patient's clinical course was typical for FA with progression to bone marrow failure, and death from acute myelomonocytic leukemia (AML-M4) at 9 years of age. Mutation analysis also detected a likely somatic c.2608G > A (p.Gly870Ser) in the SETBP1 gene. Consistent copy number losses of 7q and 18p and gains of 3q and 21q and accumulated non-clonal single cell chromosomal abnormalities were detected in blood leukocytes as her FA progressed. This is the first Chinese FA-L case caused by a novel FANCL mutation. The somatic gene mutation and copy number aberrations could be used to monitor disease progression and the clinical findings provide further information for genotype-phenotype correlation for FA-L. Copyright © 2017 Elsevier Masson SAS. All rights reserved.

FANCJ Helicase Operates in the Fanconi Anemia DNA Repair Pathway and the Response to Replicational Stress

PubMed Central

Wu, Yuliang; Brosh, Robert M.

2009-01-01

Fanconi anemia (FA) is an autosomal recessive disorder characterized by multiple congenital anomalies, progressive bone marrow failure, and high cancer risk. Cells from FA patients exhibit spontaneous chromosomal instability and hypersensitivity to DNA interstrand cross-linking (ICL) agents. Although the precise mechanistic details of the FA/BRCA pathway of ICL-repair are not well understood, progress has been made in the identification of the FA proteins that are required for the pathway. Among the 13 FA complementation groups from which all the FA genes have been cloned, only a few of the FA proteins are predicted to have direct roles in DNA metabolism. One of the more recently identified FA proteins, shown to be responsible for complementation of the FA complementation group J, is the BRCA1 Associated C-terminal Helicase (BACH1, designated FANCJ), originally identified as a protein associated with breast cancer. FANCJ has been proposed to function downstream of FANCD2 monoubiquitination, a critical event in the FA pathway. Evidence supports a role for FANCJ in a homologous recombination (HR) pathway of double strand break (DSB) repair. In this review, we will summarize the current knowledge in terms of FANCJ functions through its enzymatic activities and protein interactions. The molecular roles of FANCJ in DNA repair and the response to replicational stress will be discussed. PMID:19519404

Relationship between suicidality and impulsivity in bipolar I disorder: a diffusion tensor imaging study

PubMed Central

Mahon, Katie; Burdick, Katherine E; Wu, Jinghui; Ardekani, Babak A; Szeszko, Philip R

2012-01-01

Background Impulsivity is characteristic of individuals with bipolar disorder and may be a contributing factor to the high rate of suicide in patients with this disorder. Although white matter abnormalities have been implicated in the pathophysiology of bipolar disorder, their relationship to impulsivity and suicidality in this disorder has not been well-investigated. Methods Diffusion tensor imaging scans were acquired in 14 bipolar disorder patients with a prior suicide attempt, 15 bipolar disorder patients with no prior suicide attempt, and 15 healthy volunteers. Bipolar disorder patients received clinical assessments including measures of impulsivity, depression, mania, and anxiety. Images were processed using the Tract-Based Spatial Statistics method in the FSL software package. Results Bipolar disorder patients with a prior suicide attempt had lower fractional anisotropy (FA) within the left orbital frontal white matter (p < 0.05, corrected) and higher overall impulsivity compared to patients without a previous suicide attempt. Among patients with a prior suicide attempt, FA in the orbital frontal white matter region correlated inversely with motor impulsivity. Conclusions Abnormal orbital frontal white matter may play a role in impulsive and suicidal behavior among patients with bipolar disorder. PMID:22329475

Synergistic antidepressant-like effect of ferulic acid in combination with piperine: involvement of monoaminergic system

PubMed Central

Li, Gaowen; Ruan, Lina; Chen, Ruijie; Wang, Renye; Xie, Xupei; Zhang, Meixi; Chen, Lichao; Yan, Qizhi; Reed, Miranda; Chen, Jiechun; Xu, Ying; Pan, Jianchun; Huang, Wu

2016-01-01

The lifetime prevalence rate for major depressive disorder (MDD) is approximately 17 % for most developed countries around the world. Dietary polyphenols are currently used as an adjuvant therapy to accelerate the therapeutic efficacy on depression. Ferulic acid (FA) or 4-hydroxy-3-methoxy-cinnamic acid (Fig. 1a) is a main polyphenolic component of Chinese herb Radix Angelicae Sinensis, which is found to have antidepressant-like effects through regulating serotonergic and noradrenergic function. The present study examined the synergistic effect of low doses of FA combined with subthreshold dose of piperine, a bioavailability enhancer, on depression-like behaviors in mice, and investigated the possible mechanism. The administration of FA, even in the highest dose tested, reduced immobility time by 60 % in the tail suspension and forced swimming tests (TST and FST) in mice when compared to control. The maximal antidepressant-like effect of FA was obtained with 200 mg/kg. In addition, piperine only produced a weak antidepressant-like effect in the TST and FST. However, the evidence from the interaction analysis suggested a synergistic effect when low doses of FA were combined with a subthreshold dose of piperine. Further neurochemical evidence such as monoamine levels in the frontal cortex, hippocampus, and hypothalamus and measurements of monoamine oxidase activity also supported a synergistic effect of FA and piperine in the enhancement of monoaminergic function. This finding supports the concept that the combination strategy might be an alternative therapy in the treatment of psychiatric disorders with high efficacy and low side effects. PMID:26220010

Clinical, Functional, and Biological Correlates of Cognitive Dimensions in Major Depressive Disorder – Rationale, Design, and Characteristics of the Cognitive Function and Mood Study (CoFaM-Study)

PubMed Central

Baune, Bernhard T.; Air, Tracy

2016-01-01

Cross-sectional and longitudinal studies exploring clinical, functional, and biological correlates of major depressive disorder are frequent. In this type of research, depression is most commonly defined as a categorical diagnosis based on studies using diagnostic instruments. Given the phenotypic and biological heterogeneity of depression, we chose to focus the phenotypic assessments on three cognitive dimensions of depression including (a) cognitive performance, (b) emotion processing, and (c) social cognitive functioning. Hence, the overall aim of the study is to investigate the long-term clinical course of these cognitive dimensions in depression and its functional (psychosocial) correlates. We also aim to identify biological “genomic” correlates of these three cognitive dimensions of depression. To address the above overall aim, we created the Cognition and Mood Study (CoFaMS) with the key objective to investigate the clinical, functional, and biological correlates of cognitive dimensions of depression by employing a prospective study design and including a healthy control group. The study commenced in April 2015, including patients with a primary diagnosis of a major depressive episode of major depressive disorder or bipolar disorder according to DSM-IV-TR criteria. The assessments cover the three cognitive dimensions of depression (cognitive performance, emotion processing, and social cognition), cognitive function screening instrument, plus functional scales to assess general, work place, and psychosocial function, depression symptom scales, and clinical course of illness. Blood is collected for comprehensive genomic discovery analyses of biological correlates of cognitive dimensions of depression. The CoFaM-Study represents an innovative approach focusing on cognitive dimensions of depression and its functional and biological “genomic” correlates. The CoFaMS team welcomes collaborations with both national and international researchers. PMID:27616997

Clinical, Functional, and Biological Correlates of Cognitive Dimensions in Major Depressive Disorder - Rationale, Design, and Characteristics of the Cognitive Function and Mood Study (CoFaM-Study).

PubMed

Baune, Bernhard T; Air, Tracy

2016-01-01

Cross-sectional and longitudinal studies exploring clinical, functional, and biological correlates of major depressive disorder are frequent. In this type of research, depression is most commonly defined as a categorical diagnosis based on studies using diagnostic instruments. Given the phenotypic and biological heterogeneity of depression, we chose to focus the phenotypic assessments on three cognitive dimensions of depression including (a) cognitive performance, (b) emotion processing, and (c) social cognitive functioning. Hence, the overall aim of the study is to investigate the long-term clinical course of these cognitive dimensions in depression and its functional (psychosocial) correlates. We also aim to identify biological "genomic" correlates of these three cognitive dimensions of depression. To address the above overall aim, we created the Cognition and Mood Study (CoFaMS) with the key objective to investigate the clinical, functional, and biological correlates of cognitive dimensions of depression by employing a prospective study design and including a healthy control group. The study commenced in April 2015, including patients with a primary diagnosis of a major depressive episode of major depressive disorder or bipolar disorder according to DSM-IV-TR criteria. The assessments cover the three cognitive dimensions of depression (cognitive performance, emotion processing, and social cognition), cognitive function screening instrument, plus functional scales to assess general, work place, and psychosocial function, depression symptom scales, and clinical course of illness. Blood is collected for comprehensive genomic discovery analyses of biological correlates of cognitive dimensions of depression. The CoFaM-Study represents an innovative approach focusing on cognitive dimensions of depression and its functional and biological "genomic" correlates. The CoFaMS team welcomes collaborations with both national and international researchers.

Disorganization of white matter architecture in major depressive disorder: a meta-analysis of diffusion tensor imaging with tract-based spatial statistics.

PubMed

Chen, Guangxiang; Hu, Xinyu; Li, Lei; Huang, Xiaoqi; Lui, Su; Kuang, Weihong; Ai, Hua; Bi, Feng; Gu, Zhongwei; Gong, Qiyong

2016-02-24

White matter (WM) abnormalities have long been suspected in major depressive disorder (MDD). Tract-based spatial statistics (TBSS) studies have detected abnormalities in fractional anisotropy (FA) in MDD, but the available evidence has been inconsistent. We performed a quantitative meta-analysis of TBSS studies contrasting MDD patients with healthy control subjects (HCS). A total of 17 studies with 18 datasets that included 641 MDD patients and 581 HCS were identified. Anisotropic effect size-signed differential mapping (AES-SDM) meta-analysis was performed to assess FA alterations in MDD patients compared to HCS. FA reductions were identified in the genu of the corpus callosum (CC) extending to the body of the CC and left anterior limb of the internal capsule (ALIC) in MDD patients relative to HCS. Descriptive analysis of quartiles, sensitivity analysis and subgroup analysis further confirmed these findings. Meta-regression analysis revealed that individuals with more severe MDD were significantly more likely to have FA reductions in the genu of the CC. This study provides a thorough profile of WM abnormalities in MDD and evidence that interhemispheric connections and frontal-striatal-thalamic pathways are the most convergent circuits affected in MDD.

Acquisition of relative interstrand crosslinker resistance and PARP inhibitor sensitivity in Fanconi anemia head and neck cancers

PubMed Central

Lombardi, Anne J.; Hoskins, Elizabeth E.; Foglesong, Grant D.; Wikenheiser-Brokamp, Kathryn A.; Wiesmüller, Lisa; Hanenberg, Helmut; Andreassen, Paul R.; Jacobs, Allison J.; Olson, Susan B.; Keeble, Winifred W.; Hays, Laura E.; Wells, Susanne I.

2015-01-01

Purpose Fanconi anemia (FA) is an inherited disorder associated with a constitutional defect in the FA DNA repair machinery that is essential for resolution of DNA interstrand crosslinks. Individuals with FA are predisposed to formation of head and neck squamous cell carcinomas (HNSCCs) at a young age. Prognosis is poor, partly due to patient intolerance of chemotherapy and radiation requiring dose reduction, which may lead to early recurrence of disease. Experimental Design Using HNSCC cell lines derived from the tumors of FA patients, and murine HNSCC cell lines derived from the tumors of wild type and Fancc−/− mice, we sought to define FA-dependent chemosensitivity and DNA repair characteristics. We utilized DNA repair reporter assays to explore the preference of FA HNSCC cells for non-homologous end joining (NHEJ). Results Surprisingly, interstrand crosslinker (ICL) sensitivity was not necessarily FA-dependent in human or murine cell systems. Our results suggest that the increased Ku-dependent NHEJ that is expected in FA cells did not mediate relative ICL resistance. ICL exposure resulted in increased DNA damage sensing and repair by poly(ADP-ribose) polymerase (PARP) in FA-deficient cells. Moreover, human and murine FA HNSCC cells were sensitive to PARP inhibition, and sensitivity of human cells was attenuated by FA gene complementation. Conclusions The observed reliance upon PARP-mediated mechanisms reveals a means by which FA HNSCCs can acquire relative resistance to the ICL-based chemotherapy that is a foundation of HNSCC treatment, as well as a potential target for overcoming chemoresistance in the chemosensitive individual. PMID:25609062

Limbic and corpus callosum aberrations in adolescents with bipolar disorder: a tract-based spatial statistics analysis.

PubMed

Barnea-Goraly, Naama; Chang, Kiki D; Karchemskiy, Asya; Howe, Meghan E; Reiss, Allan L

2009-08-01

Bipolar disorder (BD) is a common and debilitating condition, often beginning in adolescence. Converging evidence from genetic and neuroimaging studies indicates that white matter abnormalities may be involved in BD. In this study, we investigated white matter structure in adolescents with familial bipolar disorder using diffusion tensor imaging (DTI) and a whole brain analysis. We analyzed DTI images using tract-based spatial statistics (TBSS), a whole-brain voxel-by-voxel analysis, to investigate white matter structure in 21 adolescents with BD, who also were offspring of at least one parent with BD, and 18 age- and IQ-matched control subjects. Fractional anisotropy (FA; a measure of diffusion anisotropy), trace values (average diffusivity), and apparent diffusion coefficient (ADC; a measure of overall diffusivity) were used as variables in this analysis. In a post hoc analysis, we correlated between FA values, behavioral measures, and medication exposure. Adolescents with BD had lower FA values than control subjects in the fornix, the left mid-posterior cingulate gyrus, throughout the corpus callosum, in fibers extending from the fornix to the thalamus, and in parietal and occipital corona radiata bilaterally. There were no significant between-group differences in trace or ADC values and no significant correlation between behavioral measures, medication exposure, and FA values. Significant white matter tract alterations in adolescents with BD were observed in regions involved in emotional, behavioral, and cognitive regulation. These results suggest that alterations in white matter are present early in the course of disease in familial BD.

Fatty acid profile of the initial oral biofilm (pellicle): an in-situ study.

PubMed

Reich, Marco; Kümmerer, Klaus; Al-Ahmad, Ali; Hannig, Christian

2013-09-01

The first step of bioadhesion on dental surfaces is the formation of the acquired pellicle. This mainly acellular layer is formed instantaneously on all solid surfaces exposed to oral fluids. It is composed of proteins, glycoproteins and lipids. However, information on the lipid composition is sparse. The aim of the present study was to evaluate the fatty acid (FA) profile of the in-situ pellicle for the first time. Furthermore, the impact of rinses with safflower oil on the pellicle's FA composition was investigated. Pellicles were formed in situ on bovine enamel slabs mounted on individual upper jaw splints. The splints were carried by ten subjects over durations of 3-240 min. After comprehensive sample preparation, gas chromatography coupled with electron impact ionization mass spectrometry (GC-EI/MS) was used in order to characterize qualitatively and quantitatively a wide range of FA (C12-C24). The relative FA profiles of the pellicle samples gained from different subjects were remarkably similar, whereas the amount of FA showed significant interindividual variability. An increase in FA in the pellicle was observed over time. The application of rinses with safflower oil resulted in an accumulation of its specific FA in the pellicle. Pellicle formation is a highly selective process that does not correlate directly with salivary composition, as shown for FA.

Occurrence and photodegradation of methylmercury in surface water of Wen-Rui-Tang River network, Wenzhou, China.

PubMed

Pan, Shuihong; Feng, Chuchu; Lin, Jialu; Cheng, Lidong; Wang, Chengjun; Zuo, Yuegang

2017-04-01

The spatial distribution and seasonal variations of methylmercury (MeHg) in Wen-Rui-Tang (WRT) River network were investigated by monitoring the MeHg concentrations in surface water samples collected from 30 sites across the river network over four seasons. Detection frequencies and concentrations of MeHg were generally higher in January, indicating that low sunlight irradiation, wind speed, and temperature conditions might enhance the persistence of MeHg in surface water. The MeHg levels varied with sampling locations, with the highest concentrations being observed in the industrial area especially around wastewater outfall, revealing that the mercury contamination in WRT River mainly comes from the industrial wastewater. Photodegradation of MeHg in WRT River surface water and the effects of natural constituents such as fulvic acid (FA), ferric ions (Fe 3+ ), nitrate (NO 3 - ), and dissolved oxygen on the MeHg photodegradation in aqueous solutions were studied under the simulated sunlight. The experimental data indicated that the indirect photodecomposition of MeHg occurred in WRT River surface water. Photodegradation of MeHg in FA solution was initiated by triplet 3 FA* or MeHg-FA* via electron transfer interaction under light irradiations. The Fe 3+ and NO 3 - can absorb light energy to produce ·OH and enhance the photochemical degradation of MeHg. The MeHg photodecompositions in FA, nitrate, and Fe 3+ solutions were markedly accelerated after removing the dissolved oxygen.

Tool use in left brain damage and Alzheimer's disease: What about function and manipulation knowledge?

PubMed

Jarry, Christophe; Osiurak, François; Besnard, Jérémy; Baumard, Josselin; Lesourd, Mathieu; Croisile, Bernard; Etcharry-Bouyx, Frédérique; Chauviré, Valérie; Le Gall, Didier

2016-03-01

Tool use disorders are usually associated with difficulties in retrieving function and manipulation knowledge. Here, we investigate tool use (Real Tool Use, RTU), function (Functional Association, FA) and manipulation knowledge (Gesture Recognition, GR) in 17 left-brain-damaged (LBD) patients and 14 AD patients (Alzheimer disease). LBD group exhibited predicted deficit on RTU but not on FA and GR while AD patients showed deficits on GR and FA with preserved tool use skills. These findings question the role played by function and manipulation knowledge in actual tool use. © 2016 The British Psychological Society.

FANCD2 monoubiquitination and activation by hexavalent chromium [Cr(VI)] exposure

PubMed Central

Vilcheck, Susan K.; Ceryak, Susan; O’Brien, Travis J.; Patierno, Steven R.

2007-01-01

Fanconi anemia (FA) is a rare autosomal recessive disorder characterized by congenital abnormalities, progressive bone marrow failure, and cancer susceptibility. FA cells are hypersensitive to DNA crosslinking agents. FA is a genetically heterogeneous disease with at least 11 complementation groups. The eight cloned FA proteins interact in a common pathway with established DNA-damage-response proteins, including BRCA1 and ATM. Six FA proteins (A, C, E, F, G, and L) regulate the monoubiquitination of FANCD2 after DNA damage by crosslinking agents, which targets FANCD2 to BRCA1 nuclear foci containing BRCA2 (FANCD1) and RAD51. Some forms of hexavalent chromium [Cr(VI)] are implicated as respiratory carcinogens and induce several types of DNA lesions, including DNA interstrand crosslinks. We have shown that FA-A fibroblasts are hypersensitive to both Cr(VI)-induced apoptosis and clonogenic lethality. Here we show that Cr(VI) treatment induced monoubiquitination of FANCD2 in normal human fibroblasts, providing the first molecular evidence of Cr(VI)-induced activation of the FA pathway. FA-A fibroblasts demonstrated no FANCD2 monoubiquitination, in keeping with the requirement of FA-A for this modification. We also found that Cr(VI) treatment induced significantly more S-phase-dependent DNA double strand breaks (DSBs), as measured by γ-H2AX expression, in FA-A fibroblasts compared to normal cells. However, and notably, DSBs were repaired equally in both normal and FA-A fibroblasts during recovery from Cr(VI) treatment. While previous research on FA has defined the genetic causes of this disease, it is critical in terms of individual risk assessment to address how cells from FA patients respond to genotoxic insult. PMID:16893675

Association of complementation group and mutation type with clinical outcome in fanconi anemia. European Fanconi Anemia Research Group.

PubMed

Faivre, L; Guardiola, P; Lewis, C; Dokal, I; Ebell, W; Zatterale, A; Altay, C; Poole, J; Stones, D; Kwee, M L; van Weel-Sipman, M; Havenga, C; Morgan, N; de Winter, J; Digweed, M; Savoia, A; Pronk, J; de Ravel, T; Jansen, S; Joenje, H; Gluckman, E; Mathew, C G

2000-12-15

Fanconi anemia (FA) is a clinically and genetically heterogeneous disorder. Clinical care is complicated by variable age at onset and severity of hematologic symptoms. Recent advances in the molecular biology of FA have allowed us to investigate the relationship between FA genotype and the nature and severity of the clinical phenotype. Two hundred forty-five patients from all 7 known complementation groups (FA-A to FA-G) were studied. Mutations were detected in one of the cloned FANC genes in 169 patients; in the remainder the complementation group was assigned by cell fusion or Western blotting. A range of qualitative and quantitative clinical parameters was compared for each complementation group and for different classes of mutation. Significant phenotypic differences were found. FA-G patients had more severe cytopenia and a higher incidence of leukemia. Somatic abnormalities were less prevalent in FA-C, but more common in the rare groups FA-D, FA-E, and FA-F. In FA-A, patients homozygous for null mutations had an earlier onset of anemia and a higher incidence of leukemia than those with mutations producing an altered protein. In FA-C, there was a later age of onset of aplastic anemia and fewer somatic abnormalities in patients with the 322delG mutation, but there were more somatic abnormalities in patients with IVS4 + 4A --> T. This study indicates that FA patients with mutations in the FANCG gene and patients homozygous for null mutations in FANCA are high-risk groups with a poor hematologic outcome and should be considered as candidates both for frequent monitoring and early therapeutic intervention. (Blood. 2000;96:4064-4070)

Deletion of Fanca or Fancd2 dysregulates Treg in mice.

PubMed

Du, Wei; Erden, Ozlem; Wilson, Andrew; Sipple, Jared M; Schick, Jonathan; Mehta, Parinda; Myers, Kasiani C; Steinbrecher, Kris A; Davies, Stella M; Pang, Qishen

2014-03-20

Fanconi anemia (FA) is a genetic disorder associated with bone marrow (BM) failure and leukemia. Recent studies demonstrate variable immune defects in FA. However, the cause for FA immunodeficiency is unknown. Here we report that deletion of Fanca or Fancd2 dysregulates the suppressive activity of regulatory T cells (Tregs), shown functionally as exacerbation of graft-vs-host disease (GVHD) in mice. Recipient mice of Fanca(-/-) or Fancd2(-/-) BM chimeras exhibited severe acute GVHD after allogeneic BM transplantation (BMT). T cells from Fanca(-/-) or Fancd2(-/-) mice induced higher GVHD lethality than those from wild-type (WT) littermates. FA Tregs possessed lower proliferative suppression potential compared with WT Tregs, as demonstrated by in vitro proliferation assay and BMT. Analysis of CD25(+)Foxp3(+) Tregs indicated that loss of Fanca or Fancd2 dysregulated Foxp3 target gene expression. Additionally, CD25(+)Foxp3(+) Tregs of Fanca(-/-) or Fancd2(-/-) mice were less efficient in suppressing the production of GVHD-associated inflammatory cytokines. Consistently, aberrant NF-κB activity was observed in infiltrated T cells from FA GVHD mice. Conditional deletion of p65 in FA Tregs decreased GVHD mortality. Our study uncovers an essential role for FA proteins in maintaining Treg homeostasis, possibly explaining, at least in part, the immune deficiency reported in some FA patients.

Evaluation of antitumor effects of folate-conjugated methyl-β-cyclodextrin in melanoma.

PubMed

Motoyama, Keiichi; Onodera, Risako; Tanaka, Nao; Kameyama, Kazuhisa; Higashi, Taishi; Kariya, Ryusho; Okada, Seiji; Arima, Hidetoshi

2015-01-01

Melanoma is a life-threatening disorder and its incidence is increasing gradually. Despite the numerous treatment approaches, conventional systemic chemotherapy has not reduced the mortality rate among melanoma patients, probably due to the induction of toxicity to normal tissues. Recently, we have developed folate-conjugated methyl-β-cyclodextrin (FA-M-β-CyD) and clarified its potential as a new antitumor agent involved in autophagic cell death. However, it remains uncertain whether FA-M-β-CyD exerts anticancer effects against melanomas. Therefore, in this study, we investigated the effects of FA-M-β-CyD on the folate receptor-α (FR-α)-expressing melanoma cell-selective cytotoxic effect. FA-M-β-CyD showed cytotoxic effects in Ihara cells, a human melanoma cell line expressing FR-α. In sharp contrast to methyl-β-cyclodextrin, FA-M-β-CyD entered Ihara cells [FR-α(+)] through FR-α-mediated endocytosis. Additionally, FA-M-β-CyD elicited the formation of autophagosomes in Ihara cells. Notably, FA-M-β-CyD suppressed melanoma growth in BALB/c nude recombinase-activating gene-2 (Rag-2)/Janus kinase 3 (Jak3) double deficient mice bearing Ihara cells. Therefore, these results suggest that FA-M-β-CyD could be utilized as a potent anticancer agent for melanoma chemotherapy by regulating autophagy.

Modeling the binding of fulvic acid by goethite: the speciation of adsorbed FA molecules

NASA Astrophysics Data System (ADS)

Filius, Jeroen D.; Meeussen, Johannes C. L.; Lumsdon, David G.; Hiemstra, Tjisse; van Riemsdijk, Willem H.

2003-04-01

Under natural conditions, the adsorption of ions at the solid-water interface may be strongly influenced by the adsorption of organic matter. In this paper, we describe the adsorption of fulvic acid (FA) by metal(hydr)oxide surfaces with a heterogeneous surface complexation model, the ligand and charge distribution (LCD) model. The model is a self-consistent combination of the nonideal competitive adsorption (NICA) equation and the CD-MUSIC model. The LCD model can describe simultaneously the concentration, pH, and salt dependency of the adsorption with a minimum of only three adjustable parameters. Furthermore, the model predicts the coadsorption of protons accurately for an extended range of conditions. Surface speciation calculations show that almost all hydroxyl groups of the adsorbed FA molecules are involved in outer sphere complexation reactions. The carboxylic groups of the adsorbed FA molecule form inner and outer sphere complexes. Furthermore, part of the carboxylate groups remain noncoordinated and deprotonated.

The FA pathway counteracts oxidative stress through selective protection of antioxidant defense gene promoters.

PubMed

Du, Wei; Rani, Reena; Sipple, Jared; Schick, Jonathan; Myers, Kasiani C; Mehta, Parinda; Andreassen, Paul R; Davies, Stella M; Pang, Qishen

2012-05-03

Oxidative stress has been implicated in the pathogenesis of many human diseases including Fanconi anemia (FA), a genetic disorder associated with BM failure and cancer. Here we show that major antioxidant defense genes are down-regulated in FA patients, and that gene down-regulation is selectively associated with increased oxidative DNA damage in the promoters of the antioxidant defense genes. Assessment of promoter activity and DNA damage repair kinetics shows that increased initial damage, rather than a reduced repair rate, contributes to the augmented oxidative DNA damage. Mechanistically, FA proteins act in concert with the chromatin-remodeling factor BRG1 to protect the promoters of antioxidant defense genes from oxidative damage. Specifically, BRG1 binds to the promoters of the antioxidant defense genes at steady state. On challenge with oxidative stress, FA proteins are recruited to promoter DNA, which correlates with significant increase in the binding of BRG1 within promoter regions. In addition, oxidative stress-induced FANCD2 ubiquitination is required for the formation of a FA-BRG1-promoter complex. Taken together, these data identify a role for the FA pathway in cellular antioxidant defense.

Paclitaxel loaded magnetic nanocomposites with folate modified chitosan/carboxymethyl surface; a vehicle for imaging and targeted drug delivery.

PubMed

Bano, Shazia; Afzal, Muhammad; Waraich, Mustansar Mahmood; Alamgir, Khalid; Nazir, Samina

2016-11-20

In this study, Paclitaxel (PTX) containing, bovine serum albumin (BSA) nanoparticles were fabricated via a simple approach. Folic acid (FA) was conjugated to chitosan (CS)/carboxymethyl cellulose (CMC) through an esterification reaction to produce BSA-CS-FA or BSA-CMC-FA conjugates. NiFe 2 O 4 noncore (NFs) and PTX were loaded through a heat treatment and by a diffusion process. NFs-BSA-CS and NFs-BSA-CMC-FA with size of about 80nm, showed superior transversal R 2 relaxation rate of 349 (mM) -1 s -1 along with folate receptor-targeted and magnetically directed functions. NFs-BSA-CS-FA or NFs-BSA-CS-FA were found stable and biocompatible. Application of an external magnetic field effectively enhanced the PTX release from PTX-NFs-BSA-CS-FA or PTX-NFs-BSA-CS-FA and hence tumor inhibition rate. This study validate that NFs-BSA-CS-FA or NFs-BSA-CMC-FA and PTX-NFs-BSA-CS-FA or PTX-NFs-BSA-CS-FA are suitable systems for tumor diagnosis and therapy. Copyright © 2016. Published by Elsevier B.V.

In-vitro biocompatibility, bioactivity, and mechanical strength of PMMA-PCL polymer containing fluorapatite and graphene oxide bone cements.

PubMed

Pahlevanzadeh, F; Bakhsheshi-Rad, H R; Hamzah, E

2018-06-01

In this study, a bone cement consisting of poly methyl methacrylate (PMMA)-poly caprolactone (PCL)-fluorapatite (FA)-graphene oxide (GO) was synthesized as bone filler for application in orthopedic surgeries. The FA and GO particulates were homogenously distributed in the PMMA-PCL polymer matrix and no defects and agglomeration were found in the PMMA-PCL/FA/GO bone cement. The in-vitro bioactivity result exhibited that addition of FA and GO to the polymer cement (PMMA-PCL) improved the apatite formation ability on the surface of polymer. The results also showed that addition of FA to the polymer bone cement escalated the compressive strength and elastic modulus while reducing elongation to 8 ± 2%. However, after addition of GO into the PMMA-PCL/FA bone cement, both compressive strength and elongation considerably increased to 101 ± 5 MPa and 35 ± 6%, respectively. Furthermore, tensile tests exhibited that inclusion of GO was favorable in improving the tensile modulus, UTS and elongation of the PMMA-PCL/FA bone cement. The cytotoxicity test pointed out that MG63 osteoblast cells viability increased to 279 ± 15% after addition of FA and GO to the PMMA-PCL polymer bone cement. The DAPI (4',6-diamidino-2-phenylindole) staining demonstrated better spreading and attachment of MG63 cells on PMMA-PCL/FA/GO surface compared to the PMMA-PCL bone cements. These results confirm the suitable mechanical properties and favorable bioactivity along with high cells viability of PMMA-PCL/FA/GO bone cement, indicating its potentials for orthopedic applications. Copyright © 2018 Elsevier Ltd. All rights reserved.

Elevated left and reduced right orbitomedial prefrontal fractional anisotropy in adults with bipolar disorder revealed by tract-based spatial statistics.

PubMed

Versace, Amelia; Almeida, Jorge R C; Hassel, Stefanie; Walsh, Nicholas D; Novelli, Massimiliano; Klein, Crystal R; Kupfer, David J; Phillips, Mary L

2008-09-01

Diffusion tensor imaging (DTI) studies in adults with bipolar disorder (BD) indicate altered white matter (WM) in the orbitomedial prefrontal cortex (OMPFC), potentially underlying abnormal prefrontal corticolimbic connectivity and mood dysregulation in BD. To use tract-based spatial statistics (TBSS) to examine WM skeleton (ie, the most compact whole-brain WM) in subjects with BD vs healthy control subjects. Cross-sectional, case-control, whole-brain DTI using TBSS. University research institute. Fifty-six individuals, 31 having a DSM-IV diagnosis of BD type I (mean age, 35.9 years [age range, 24-52 years]) and 25 controls (mean age, 29.5 years [age range, 19-52 years]). Fractional anisotropy (FA) longitudinal and radial diffusivities in subjects with BD vs controls (covarying for age) and their relationships with clinical and demographic variables. Subjects with BD vs controls had significantly greater FA (t > 3.0, P 3.0, P

A novel Fanconi anaemia subtype associated with a dominant-negative mutation in RAD51

PubMed Central

Ameziane, Najim; May, Patrick; Haitjema, Anneke; van de Vrugt, Henri J.; van Rossum-Fikkert, Sari E.; Ristic, Dejan; Williams, Gareth J.; Balk, Jesper; Rockx, Davy; Li, Hong; Rooimans, Martin A.; Oostra, Anneke B.; Velleuer, Eunike; Dietrich, Ralf; Bleijerveld, Onno B.; Maarten Altelaar, A. F.; Meijers-Heijboer, Hanne; Joenje, Hans; Glusman, Gustavo; Roach, Jared; Hood, Leroy; Galas, David; Wyman, Claire; Balling, Rudi; den Dunnen, Johan; de Winter, Johan P.; Kanaar, Roland; Gelinas, Richard; Dorsman, Josephine C.

2015-01-01

Fanconi anaemia (FA) is a hereditary disease featuring hypersensitivity to DNA cross-linker-induced chromosomal instability in association with developmental abnormalities, bone marrow failure and a strong predisposition to cancer. A total of 17 FA disease genes have been reported, all of which act in a recessive mode of inheritance. Here we report on a de novo g.41022153G>A; p.Ala293Thr (NM_002875) missense mutation in one allele of the homologous recombination DNA repair gene RAD51 in an FA-like patient. This heterozygous mutation causes a novel FA subtype, ‘FA-R', which appears to be the first subtype of FA caused by a dominant-negative mutation. The patient, who features microcephaly and mental retardation, has reached adulthood without the typical bone marrow failure and paediatric cancers. Together with the recent reports on RAD51-associated congenital mirror movement disorders, our results point to an important role for RAD51-mediated homologous recombination in neurodevelopment, in addition to DNA repair and cancer susceptibility. PMID:26681308

Development of a General Aza-Cope Reaction Trigger Applied to Fluorescence Imaging of Formaldehyde in Living Cells.

PubMed

Bruemmer, Kevin J; Walvoord, Ryan R; Brewer, Thomas F; Burgos-Barragan, Guillermo; Wit, Niek; Pontel, Lucas B; Patel, Ketan J; Chang, Christopher J

2017-04-19

Formaldehyde (FA) is a reactive signaling molecule that is continuously produced through a number of central biological pathways spanning epigenetics to one-carbon metabolism. On the other hand, aberrant, elevated levels of FA are implicated in disease states ranging from asthma to neurodegenerative disorders. In this context, fluorescence-based probes for FA imaging are emerging as potentially powerful chemical tools to help disentangle the complexities of FA homeostasis and its physiological and pathological contributions. Currently available FA indicators require direct modification of the fluorophore backbone through complex synthetic considerations to enable FA detection, often limiting the generalization of designs to other fluorophore classes. To address this challenge, we now present the rational, iterative development of a general reaction-based trigger utilizing 2-aza-Cope reactivity for selective and sensitive detection of FA in living systems. Specifically, we developed a homoallylamine functionality that can undergo a subsequent self-immolative β-elimination, creating a FA-responsive trigger that is capable of masking a phenol on a fluorophore or any other potential chemical scaffold for related imaging and/or therapeutic applications. We demonstrate the utility of this trigger by creating a series of fluorescent probes for FA with excitation and emission wavelengths that span the UV to visible spectral regions through caging of a variety of dye units. In particular, Formaldehyde Probe 573 (FAP573), based on a resorufin scaffold, is the most red-shifted and FA sensitive in this series in terms of signal-to-noise responses and enables identification of alcohol dehydrogenase 5 (ADH5) as an enzyme that regulates FA metabolism in living cells. The results provide a starting point for the broader use of 2-aza-Cope reactivity for probing and manipulating FA biology.

A Whole-Brain Investigation of White Matter Microstructure in Adolescents with Conduct Disorder.

PubMed

Sarkar, Sagari; Dell'Acqua, Flavio; Froudist Walsh, Seán; Blackwood, Nigel; Scott, Stephen; Craig, Michael C; Deeley, Quinton; Murphy, Declan G M

2016-01-01

The biological basis of severe antisocial behaviour in adolescents is poorly understood. We recently reported that adolescents with conduct disorder (CD) have significantly increased fractional anisotropy (FA) of the uncinate fasciculus (a white matter (WM) tract that connects the amygdala to the frontal lobe) compared to their non-CD peers. However, the extent of WM abnormality in other brain regions is currently unclear. We used tract-based spatial statistics to investigate whole brain WM microstructural organisation in 27 adolescent males with CD, and 21 non-CD controls. We also examined relationships between FA and behavioural measures. Groups did not differ significantly in age, ethnicity, or substance use history. The CD group, compared to controls, had clusters of significantly greater FA in 7 brain regions corresponding to: 1) the bilateral inferior and superior cerebellar peduncles, corticopontocerebellar tract, posterior limb of internal capsule, and corticospinal tract; 2) right superior longitudinal fasciculus; and 3) left cerebellar WM. Severity of antisocial behavior and callous-unemotional symptoms were significantly correlated with FA in several of these regions across the total sample, but not in the CD or control groups alone. Adolescents with CD have significantly greater FA than controls in WM regions corresponding predominantly to the fronto-cerebellar circuit. There is preliminary evidence that variation in WM microstructure may be dimensionally related to behaviour problems in youngsters. These findings are consistent with the hypothesis that antisocial behaviour in some young people is associated with abnormalities in WM 'connectivity'.

White matter microstructural abnormalities in the frontal lobe of adults with antisocial personality disorder.

PubMed

Sundram, Frederick; Deeley, Quinton; Sarkar, Sagari; Daly, Eileen; Latham, Richard; Craig, Michael; Raczek, Malgorzata; Fahy, Tom; Picchioni, Marco; Barker, Gareth J; Murphy, Declan G M

2012-02-01

Antisocial personality disorder (ASPD) and psychopathy involve significant interpersonal and behavioural impairments. However, little is known about their underlying neurobiology and in particular, abnormalities in white matter (WM) microstructure. A preliminary diffusion tensor magnetic resonance imaging (DT-MRI) study of adult psychopaths employing tractography revealed abnormalities in the right uncinate fasciculus (UF) (Craig et al., 2009), indicating fronto-limbic disconnectivity. However, it is not clear whether WM abnormalities are restricted to this tract or are or more widespread, including other tracts which are involved in connectivity with the frontal lobe. We performed whole brain voxel-based analyses on WM fractional anisotropy (FA) and mean diffusivity (MD) maps acquired with DT-MRI to compare 15 adults with ASPD and healthy age, handedness and IQ-matched controls. Also, within ASPD subjects we related differences in FA and MD to measures of psychopathy. Significant WM FA reduction and MD increases were found respectively in ASPD subjects relative to controls. FA was bilaterally reduced in the genu of corpus callosum while in the right frontal lobe FA reduction was found in the UF, inferior fronto-occipital fasciculus (IFOF), anterior corona radiata and anterior limb and genu of the internal capsule. These differences negatively correlated with measures of psychopathy. Also in the right frontal lobe, increased MD was found in the IFOF and UF, and the corpus callosum and anterior corona radiata. There was a significant positive correlation between MD and psychopathy scores. The present study confirms a previous report of reduced FA in the UF. Additionally, we report for the first time, FA deficits in tracts involved in interhemispheric as well as frontal lobe connectivity in conjunction with MD increases in the frontal lobe. Hence, we provide evidence of significant WM microstructural abnormalities in frontal brain regions in ASPD and psychopathy. Copyright © 2011 Elsevier Srl. All rights reserved.

The impact of CACNA1C gene, and its epistasis with ZNF804A, on white matter microstructure in health, schizophrenia and bipolar disorder1.

PubMed

Mallas, E; Carletti, F; Chaddock, C A; Shergill, S; Woolley, J; Picchioni, M M; McDonald, C; Toulopoulou, T; Kravariti, E; Kalidindi, S; Bramon, E; Murray, R; Barker, G J; Prata, D P

2017-04-01

Genome-wide studies have identified allele A (adenine) of single nucleotide polymorphism (SNP) rs1006737 of the calcium-channel CACNA1C gene as a risk factor for both schizophrenia (SZ) and bipolar disorder (BD) as well as allele A for rs1344706 in the ZNF804A gene. These illnesses have also been associated with white matter abnormalities, reflected by reductions in fractional anisotropy (FA), measured using diffusion tensor imaging (DTI). We assessed the impact of the CACNA1C psychosis risk variant on FA in SZ, BD and health. 230 individuals (with existing ZNF804A rs1344706 genotype data) were genotyped for CACNA1C rs1006737 and underwent DTI. FA data was analysed with tract-based spatial statistics and threshold-free cluster enhancement significance correction (P < 0.05) to detect effects of CACNA1C genotype on FA, and its potential interaction with ZNF804A genotype and with diagnosis, on FA. There was no significant main effect of the CACNA1C genotype on FA, nor diagnosis by genotype(s) interactions. Nevertheless, when inspecting SZ in particular, risk allele carriers had significantly lower FA than the protective genotype individuals, in portions of the left middle occipital and parahippocampal gyri, right cerebellum, left optic radiation and left inferior and superior temporal gyri. Our data suggests a minor involvement of CACNA1C rs1006737 in psychosis via conferring susceptibility to white matter microstructural abnormalities in SZ. Put in perspective, ZNF804A rs1344706, not only had a significant main effect, but its SZ-specific effects were two orders of magnitude more widespread than that of CACNA1C rs1006737. © 2016 John Wiley & Sons Ltd and International Behavioural and Neural Genetics Society.

Effect of mineral surface properties (alumina, kaolinite) on the sorptive fractionation mechanisms of soil fulvic acids: Molecular-scale ESI-MS studies

NASA Astrophysics Data System (ADS)

Fleury, Guillaume; Del Nero, Mirella; Barillon, Rémi

2017-01-01

We addressed the effects of mineral surface properties (kaolinite versus Al-oxide) on the sorption-driven fractionation of a soil fulvic acid (FA) at acidic pH, mainly by means of ESI(-)-FTMS analysis of initial and supernatant solutions of FA sorption batch experiments. The MS data provided clear molecular-scale evidence of distinct mechanisms and molecular parameters controlling the FA fractionation upon its sorption on clay and oxide surfaces, respectively. Identification of sorbing and not-sorbing FA compounds in kaolinite-solution systems revealed a weak fractionation among members of sbnd CO2 series of aliphatics or not-condensed aromatics (NCAs) at pH 3.8, and almost no sorption of poorly-oxygenated polycyclic aromatic compounds (PACs) and NCAs. This first molecular-scale description of a FA fractionation in a clay-solution system suggests that H-bonding with low affinity sites (aluminol/silanol) on the basal planes of the clay particles is the main mechanism of sorption. Due to the predominance of such weak and poorly-selective mechanism, the sorption of aliphatic and NCA molecules bearing oxygenated functionalities was prevented at pH 5, due to dissolved Al competing successfully for their coordination. In contrast, a strong FA fractionation was observed onto alumina, with a preferential retention of PACs and highly-oxygenated aliphatics and NCAs. The major part of the poorly oxygenated aliphatics was left in solution. The sorption degree of NCAs and aliphatics was strongly correlated with molecular acidity. For PACs and poorly-oxygenated NCAs, the sorption was driven by reactions of surface ligand exchange (for the most oxygenated compounds) or by hydrophobic interactions (for the least oxygenated compounds).

Multifunctional DNA-gold nanoparticles for targeted doxorubicin delivery.

PubMed

Alexander, Colleen M; Hamner, Kristen L; Maye, Mathew M; Dabrowiak, James C

2014-07-16

In this report we describe the synthesis, characterization, and cytotoxic properties of DNA-capped gold nanoparticles having attached folic acid (FA), a thermoresponsive polymer (p), and/or poly(ethylene glycol) (PEG) oligomers that could be used to deliver the anticancer drug doxorubicin (DOX) in chemotherapy. The FA-DNA oligomer used in the construction of the delivery vehicle was synthesized through the reaction of the isolated folic acid N-hydroxysuccinimide ester with the amino-DNA and the conjugated DNA product was purified using high performance liquid chromatography (HPLC). This approach ultimately allowed control of the amount of FA attached to the surface of the delivery vehicle. Cytotoxicity studies using SK-N-SH neuroblastoma cells with drug loaded delivery vehicles were carried out using a variety of exposure times (1-48 h) and recovery times (1-72 h), and in order to access the effects of varying amounts of attached FA, in culture media deficient in FA. DOX loaded delivery vehicles having 50% of the DNA strands with attached FA were more cytotoxic than when all of the strands contained FA. Since FA stimulates cell growth, the reduced cytotoxicity of vehicles fully covered with FA suggests that the stimulatory effects of FA can more than compensate for the cytotoxic effects of the drug on the cell population. While attachment of hexa-ethylene glycol PEG(18) to the surface of the delivery vehicle had no effect on cytotoxicity, 100% FA plus the thermoresponsive polymer resulted in IC50 = 0.48 ± 0.01 for an exposure time of 24 h and a recovery time of 1 h, which is an order of magnitude more cytotoxic than free DOX. Confocal microscopic studies using fluorescence detection showed that SK-N-SH neuroblastoma cells exposed to DOX-loaded vehicles have drug accumulation inside the cell and, in the case of vehicles with attached FA and thermoresponsive polymer, the drug appears more concentrated. Since the biological target of DOX is DNA, the latter observation is consistent with the high cytotoxicity of vehicles having both FA and the thermoresponsive polymer. The study highlights the potential of DNA-capped gold nanoparticles as delivery vehicles for doxorubicin in cancer chemotherapy.

Reduced white matter integrity and verbal fluency impairment in young adults with bipolar disorder: a diffusion tensor imaging study

PubMed Central

Bauer, Isabelle E.; Ouyang, Austin; Mwangi, Benson; Sanches, Marsal; Zunta-Soares, Giovana B.; Keefe, Richard S. E.; Huang, Hao; Soares, Jair C.

2015-01-01

Background Clinical evidence shows that bipolar disorder (BD) is characterized by white matter (WM) microstructural abnormalities. However, little is known about the biological mechanisms associated with these abnormalities and their relationship with cognitive functioning. Methods 49 adult BD patients ((M±SD): 29.27 ± 7.92 years; 17 males, 32 females; 34 BD-I, 10 BD-II, and 5 BD-NOS) and 28 age-matched normal subjects ((M±SD): 29.19 ± 7.35 years; 10 males and 18 females) underwent diffusion tensor imaging (DTI) imaging. DTI metrics were computed using whole-brain tract-based spatial statistics (TBSS) as part of the FMRIB Software Library. Measures of WM coherence (fractional anisotropy - FA) and axonal structure (mean, axial and radial diffusivity - MD, AD and RD) were employed to characterize the microstructural alterations in the limbic, commissural, association and projection fiber tracts. All participants performed the Brief Assessment of Cognition for Affective disorders (BAC-A). Results BD patients performed poorly on verbal fluency tasks and exhibited large clusters of altered FA, RD and MD values within the retrolenticular part of the internal capsule, the superior and anterior corona radiata, and the corpus callosum. Increased FA values in the left IFOF and the forceps minor correlated positively with verbal fluency scores. Altered RD parameters in the corticospinal tract and the forceps minor were associated with reduced visuomotor abilities. Conclusions The reported verbal fluency deficits and FA, RD and MD alterations in WM structures are potential cognitive and neural markers of BD. Abnormal RD values may be associated with progressive demyelination. PMID:25684152

Rac1 Recruitment to the Archipelago Structure of the Focal Adhesion through the Fluid Membrane as Revealed by Single-Molecule Analysis

PubMed Central

Shibata, Akihiro C E; Chen, Limin H; Nagai, Rie; Ishidate, Fumiyoshi; Chadda, Rahul; Miwa, Yoshihiro; Naruse, Keiji; Shirai, Yuki M; Fujiwara, Takahiro K; Kusumi, Akihiro

2013-01-01

The focal adhesion (FA) is an integrin-based structure built in/on the plasma membrane (PM), linking the extracellular matrix to the actin stress-fibers, working as cell migration scaffolds. Previously, we proposed the archipelago architecture of the FA, in which FA largely consists of fluid membrane, dotted with small islands accumulating FA proteins: membrane molecules enter the inter-island channels in the FA zone rather freely, and the integrins in the FA-protein islands rapidly exchanges with those in the bulk membrane. Here, we examined how Rac1, a small G-protein regulating FA formation, and its activators αPIX and βPIX, are recruited to the FA zones. PIX molecules are recruited from the cytoplasm to the FA zones directly. In contrast, majorities of Rac1 molecules first arrive from the cytoplasm on the general inner PM surface, and then enter the FA zones via lateral diffusion on the PM, which is possible due to rapid Rac1 diffusion even within the FA zones, slowed only by a factor of two to four compared with that outside. The constitutively-active Rac1 mutant exhibited temporary and all-time immobilizations in the FA zone, suggesting that upon PIX-induced Rac1 activation at the FA-protein islands, Rac1 tends to be immobilized at the FA-protein islands. © 2013 Wiley Periodicals, Inc PMID:23341328

Encyclopaedia of tumour-associated familial disorders. Part I: from AIMAH to CHIME syndrome

PubMed Central

Sijmons, Rolf H

2008-01-01

Cancer is associated with a wide range of hereditary disorders. Recognizing these disorders in cancer patients may be of great importance for the medical management of both patients and their relatives. Conversely, recognizing the fact that cancer may develop as a complication of a particular hereditary disorder which has already been diagnosed may be important for the same reason. The Familial Cancer Database (FaCD) is a web-based application which has been developed at our department with the intention to assist clinicians and genetic counsellors in making a genetic differential diagnosis in cancer patients, as well as in becoming aware of the tumour spectrum associated with hereditary disorders that have already been diagnosed in their patients. This encyclopaedia is published in parts and discusses the disorders included in the FaCD database in alphabetical order. It lists names, synonyms, OMIM number, mode of inheritance, associated genes, phenotype, clinical discussion and references. The purpose of presenting this encyclopaedia in paper format is simply that we hope that you as clinicians and researchers find it helpful to browse through it and familiarize yourself even better with the scope of genetic disorders that have been associated with increased tumour risk. PMID:19706204

The Convergent Validity of the Questions about Behavioral Function Scale and Functional Analysis for Problem Behavior Displayed by Individuals with Autism Spectrum Disorder

ERIC Educational Resources Information Center

Watkins, Nicholas; Rapp, John T.

2013-01-01

Only a few studies have compared the convergent validity of the Questions About Behavioral Function (QABF) scale to the results of functional analyses (FA). In the current study, six participants who emitted problem behaviors participated in either a brief, or a no-interaction-series FA, while each participant's parent completed the QABF. The…

Folic acid functionalized surface highlights 5-methylcytosine-genomic content within circulating tumor cells.

PubMed

Malara, Natalia; Coluccio, Maria Laura; Limongi, Tania; Asande, Monica; Trunzo, Valentina; Cojoc, Gheorghe; Raso, Cinzia; Candeloro, Patrizio; Perozziello, Gerardo; Raimondo, Raffaella; De Vitis, Stefania; Roveda, Laura; Renne, Maria; Prati, Ubaldo; Mollace, Vincenzo; Di Fabrizio, Enzo

2014-11-12

Although the detection of methylated cell free DNA represents one of the most promising approaches for relapse risk assessment in cancer patients, the low concentration of cell-free circulating DNA constitutes the biggest obstacle in the development of DNA methylation-based biomarkers from blood. This paper describes a method for the measurement of genomic methylation content directly on circulating tumor cells (CTC), which could be used to deceive the aforementioned problem. Since CTC are disease related blood-based biomarkers, they result essential to monitor tumor's stadiation, therapy, and early relapsing lesions. Within surface's bio-functionalization and cell's isolation procedure standardization, the presented approach reveals a singular ability to detect high 5-methylcytosine CTC-subset content in the whole CTC compound, by choosing folic acid (FA) as transducer molecule. Sensitivity and specificity, calculated for FA functionalized surface (FA-surface), result respectively on about 83% and 60%. FA-surface, allowing the detection and characterization of early metastatic dissemination, provides a unique advance in the comprehension of tumors progression and dissemination confirming the presence of CTC and its association with high risk of relapse. This functionalized surface identifying and quantifying high 5-methylcytosine CTC-subset content into the patient's blood lead significant progress in cancer risk assessment, also providing a novel therapeutic strategy. © 2014 WILEY-VCH Verlag GmbH & Co. KGaA, Weinheim.

Multimodal neuroimaging measures and intelligence influence pedophile child sexual offense behavior.

PubMed

Lett, Tristram A; Mohnke, Sebastian; Amelung, Till; Brandl, Eva J; Schiltz, Kolja; Pohl, Alexander; Gerwinn, Hannah; Kärgel, Christian; Massau, Claudia; Tenbergen, Gilian; Wittfoth, Matthias; Kneer, Jonas; Beier, Klaus M; Walter, Martin; Ponseti, Jorge; Krüger, Tillmann H C; Schiffer, Boris; Walter, Henrik

2018-06-04

Pedophilia is a heterogeneous disorder for which the neurobiological correlates are not well established. In particular, there are no biological markers identifying individuals with high risk to commit child sexual offense (CSO). Pedophiles with CSO (P+CSO; N = 73), pedophiles without CSO (P-CSO; N = 77), and non-pedophilic controls (NPC; N = 133) were assessed using multimodal structural neuroimaging measures including: cortical thickness (CT), surface area (SA), and white matter fractional anisotropy (FA), as well as full scale IQ (FSIQ) performance. Cortex-wise mediation analyses were used to assess the relationships among brain structure, FSIQ and CSO behavior. Lower FSIQ performance was strongly predict with P+CSO (Wald Chi 2 = 13.0, p = 3.1 × 10 -5 ). P+CSO had lower CT in the right motor cortex and pronounced reductions in SA spanning the bilateral frontal, temporal, cingulate, and insular regions (P FWE-corrected < 0.05). P+CSO also had lower FA particularly in the corpus callosum (P FWE-corrected < 0.05). The relationship between SA and P+CSO was significantly mediated by FSIQ, particularly in the prefrontal and anterior insular cortices (P FWE-corrected < 0.05). Within P+CSO, left prefrontal and right anterior cingulate SA negatively correlated with number of CSOs (P FWE-corrected < 0.05). This study demonstrates converging neurobiological findings in which P+CSO had lower FSIQ performance, reduced CT, reduced SA, and reduced FA, compared to P-CSO as well as NPC. Further, FSIQ potentially mediates abuse by pedophiles via aberrant SA, whereas the CT and FA associations were independent of FSIQ differences. These findings suggest aberrant neuroanatomy and lower intelligence as a potential core feature underlying child sexual abuse behavior by pedophiles. Copyright © 2018. Published by Elsevier B.V.

Pluripotent cell models of fanconi anemia identify the early pathological defect in human hemoangiogenic progenitors.

PubMed

Suzuki, Naoya M; Niwa, Akira; Yabe, Miharu; Hira, Asuka; Okada, Chihiro; Amano, Naoki; Watanabe, Akira; Watanabe, Ken-Ichiro; Heike, Toshio; Takata, Minoru; Nakahata, Tatsutoshi; Saito, Megumu K

2015-04-01

Fanconi anemia (FA) is a disorder of genomic instability characterized by progressive bone marrow failure (BMF), developmental abnormalities, and an increased susceptibility to cancer. Although various consequences in hematopoietic stem/progenitor cells have been attributed to FA-BMF, the quest to identify the initial pathological event is still ongoing. To address this issue, we established induced pluripotent stem cells (iPSCs) from fibroblasts of six patients with FA and FANCA mutations. An improved reprogramming method yielded iPSC-like colonies from all patients, and iPSC clones were propagated from two patients. Quantitative evaluation of the differentiation ability demonstrated that the differentiation propensity toward the hematopoietic and endothelial lineages is already defective in early hemoangiogenic progenitors. The expression levels of critical transcription factors were significantly downregulated in these progenitors. These data indicate that the hematopoietic consequences in FA patients originate from the early hematopoietic stage and highlight the potential usefulness of iPSC technology for elucidating the pathogenesis of FA-BMF. ©AlphaMed Press.

Higher limb asymmetry in deceased human fetuses and infants with aneuploidy

PubMed Central

Bots, Jessica; ten Broek, Clara M. A.; Belien, Jeroen A. M.; Bugiani, Marianna; Galis, Frietson; Van Dongen, Stefan

2014-01-01

Aneuploidies cause gene-dosage imbalances that presumably result in a generalized decreased developmental homeostasis, which is expected to be detectable through an increase in fluctuating asymmetry (FA) of bilateral symmetric traits. However, support for the link between aneuploidy and FA is currently limited and no comparisons among different aneuploidies have been made. Here, we study FA in deceased human fetuses and infants from a 20-year hospital collection. Mean FA of limb bones was compared among groups of aneuploidies with different prenatal and postnatal survival chances and two reference groups (normal karyogram or no congenital anomalies). Limb asymmetry was 1.5 times higher for aneuploid cases with generally very short life expectancies (trisomy 13, trisomy 18, monosomy X, triploidy) than for trisomy 21 patients and both reference groups with higher life expectancies. Thus, FA levels are highest in groups for which developmental disturbances have been highest. Our results show a significant relationship between fluctuating asymmetry, human genetic disorders and severity of the associated abnormalities. PMID:24424506

Calcite growth-rate inhibition by fulvic acid and magnesium ion—Possible influence on biogenic calcite formation

NASA Astrophysics Data System (ADS)

Reddy, Michael M.

2012-08-01

Increases in ocean surface water dissolved carbon dioxide (CO2) concentrations retard biocalcification by reducing calcite supersaturation (Ωc). Reduced calcification rates may influence growth-rate dependent magnesium ion (Mg) incorporation into biogenic calcite modifying the use of calcifying organisms as paleoclimate proxies. Fulvic acid (FA) at biocalcification sites may further reduce calcification rates. Calcite growth-rate inhibition by FA and Mg, two common constituents of seawater and soil water involved in the formation of biogenic calcite, was measured separately and in combination under identical, highly reproducible experimental conditions. Calcite growth rates (pH=8.5 and Ωc=4.5) are reduced by FA (0.5 mg/L) to 47% and by Mg (10-4 M) to 38%, compared to control experiments containing no added growth-rate inhibitor. Humic acid (HA) is twice as effective a calcite growth-rate inhibitor as FA. Calcite growth rate in the presence of both FA (0.5 mg/L) and Mg (10-4 M) is reduced to 5% of the control rate. Mg inhibits calcite growth rates by substitution for calcium ion at the growth site. In contrast, FA inhibits calcite growth rates by binding multiple carboxylate groups on the calcite surface. FA and Mg together have an increased affinity for the calcite growth sites reducing calcite growth rates.

Calcite growth-rate inhibition by fulvic acid and magnesium ion—Possible influence on biogenic calcite formation

USGS Publications Warehouse

Reddy, Michael M.

2012-01-01

Increases in ocean surface water dissolved carbon dioxide (CO2) concentrations retard biocalcification by reducing calcite supersaturation (Ωc). Reduced calcification rates may influence growth-rate dependent magnesium ion (Mg) incorporation into biogenic calcite modifying the use of calcifying organisms as paleoclimate proxies. Fulvic acid (FA) at biocalcification sites may further reduce calcification rates. Calcite growth-rate inhibition by FA and Mg, two common constituents of seawater and soil water involved in the formation of biogenic calcite, was measured separately and in combination under identical, highly reproducible experimental conditions. Calcite growth rates (pH=8.5 and Ωc=4.5) are reduced by FA (0.5 mg/L) to 47% and by Mg (10−4 M) to 38%, compared to control experiments containing no added growth-rate inhibitor. Humic acid (HA) is twice as effective a calcite growth-rate inhibitor as FA. Calcite growth rate in the presence of both FA (0.5 mg/L) and Mg (10−4 M) is reduced to 5% of the control rate. Mg inhibits calcite growth rates by substitution for calcium ion at the growth site. In contrast, FA inhibits calcite growth rates by binding multiple carboxylate groups on the calcite surface. FA and Mg together have an increased affinity for the calcite growth sites reducing calcite growth rates.

Impaired immune function in children and adults with Fanconi anemia.

PubMed

Myers, Kasiani C; Sauter, Sharon; Zhang, Xue; Bleesing, Jacob J; Davies, Stella M; Wells, Susanne I; Mehta, Parinda A; Kumar, Ashish; Marmer, Daniel; Marsh, Rebecca; Brown, Darron; Butsch Kovacic, Melinda

2017-11-01

Fanconi anemia (FA) is a rare genetic disorder characterized by genome instability, bone marrow failure, and cancer predisposition. Previously, small studies have reported heterogeneous immune dysfunction in FA. We performed a detailed immunologic assessment in a large FA cohort who have not undergone bone marrow transplantation or developed malignancies. Comprehensive quantitative and functional immunologic assessment of 29 FA individuals was compared to healthy age-matched controls. Compared to non-FA persons of similar ages, FA individuals showed lower absolute total B cells (P < 0.001), lower memory B cells (P < 0.001), and decreased IgM (P < 0.001) but normal IgG. NK cells (P < 0.001) and NK cytotoxicity (P < 0.001) were decreased. CD4 + T cells were decreased (P = 0.022), while CD8 + T cell and absolute T-cell numbers were comparable. Cytotoxic T cells (P < 0.003), and antigen proliferation response to tetanus (P = 0.019) and candida (P = 0.019), were diminished in FA. Phytohemagglutinin responses and plasma cytokines were normal. Within FA subjects, adults and older children (≥10 years) exhibited higher CD8 + T cells than younger children (P = 0.004). Documented atypical infections were infrequent, although oral human papilloma virus (HPV) prevalence was higher (31% positive) in FA. Overall, these results demonstrate a high rate of significant humoral and cellular immune dysfunction. Continued longitudinal study of immune function is critical to understand evolution with age, bone marrow failure, and cancer development. © 2017 Wiley Periodicals, Inc.

Deletion of Fanca or Fancd2 dysregulates Treg in mice

PubMed Central

Du, Wei; Erden, Ozlem; Wilson, Andrew; Sipple, Jared M.; Schick, Jonathan; Mehta, Parinda; Myers, Kasiani C.; Steinbrecher, Kris A.; Davies, Stella M.

2014-01-01

Fanconi anemia (FA) is a genetic disorder associated with bone marrow (BM) failure and leukemia. Recent studies demonstrate variable immune defects in FA. However, the cause for FA immunodeficiency is unknown. Here we report that deletion of Fanca or Fancd2 dysregulates the suppressive activity of regulatory T cells (Tregs), shown functionally as exacerbation of graft-vs-host disease (GVHD) in mice. Recipient mice of Fanca−/− or Fancd2−/− BM chimeras exhibited severe acute GVHD after allogeneic BM transplantation (BMT). T cells from Fanca−/− or Fancd2−/− mice induced higher GVHD lethality than those from wild-type (WT) littermates. FA Tregs possessed lower proliferative suppression potential compared with WT Tregs, as demonstrated by in vitro proliferation assay and BMT. Analysis of CD25+Foxp3+ Tregs indicated that loss of Fanca or Fancd2 dysregulated Foxp3 target gene expression. Additionally, CD25+Foxp3+ Tregs of Fanca−/− or Fancd2−/− mice were less efficient in suppressing the production of GVHD-associated inflammatory cytokines. Consistently, aberrant NF-κB activity was observed in infiltrated T cells from FA GVHD mice. Conditional deletion of p65 in FA Tregs decreased GVHD mortality. Our study uncovers an essential role for FA proteins in maintaining Treg homeostasis, possibly explaining, at least in part, the immune deficiency reported in some FA patients. PMID:24501220

FANCA and FANCG are the major Fanconi anemia genes in the Korean population.

PubMed

Park, J; Chung, N-G; Chae, H; Kim, M; Lee, S; Kim, Y; Lee, J-W; Cho, B; Jeong, D C; Park, I Y

2013-09-01

Fanconi anemia (FA) is a rare disorder characterized by physical abnormalities, bone marrow failure (BMF), increased risk of malignancies, and cellular hypersensitivity to DNA cross-linking agents. This study evaluated the genetic alterations in three major Fanconi genes (FANCA, FANCC, and FANCG) in 30 FA patients using multiplex ligation-dependent probe amplification and direct sequencing. Thirteen BMF patients were genetically classified as FA-A (n = 6, 46%) and FA-G (n = 7, 54%). Four common founder mutations were identified and included two FANCA mutations (c.2546delC and c.3720_3724delAAACA) and two FANCG mutations (c.307+1G>C and c.1066C>T), which had previously been commonly observed in a Japanese FA population. We also detected four novel deleterious mutations: c.2778+1G>C and c.3627-1G>A of FANCA, and c.1589_1591delATA and c.1761-1G>A of FANCG. This study shows that mutations in FANCA and FANCG are common in Korean FA patients and the existence of four common founder mutations in an East Asian FA population. Mutation screening workflow that includes these common mutations may be useful in the creation of an international database, and to better understand the ethnic characteristics of FA. © 2012 John Wiley & Sons A/S. Published by John Wiley & Sons Ltd.

Internet gaming disorder and online gambling disorder: Clinical and personality correlates.

PubMed

Mallorquí-Bagué, Nuria; Fernández-Aranda, Fernando; Lozano-Madrid, María; Granero, Roser; Mestre-Bach, Gemma; Baño, Marta; Pino-Gutiérrez, Amparo Del; Gómez-Peña, Mónica; Aymamí, Neus; Menchón, José M; Jiménez-Murcia, Susana

2017-12-01

Background and aims The recent growth of Internet use has led to an increase of potentially problematic behaviors that can be engaged online, such as online gambling or Internet gaming. The aim of this study is to better conceptualize Internet gaming disorder (IGD) by comparing it with gambling disorder (GD) patients who only gamble online (online GD). Methods A total of 288 adult patients (261 online GD and 27 IGD) completed self-reported questionnaires for exploring psychopathological symptoms, food addiction (FA), and personality traits. Results Both clinical groups presented higher psychopathological scores and less functional personality traits when compared with a normative Spanish population. However, when comparing IGD to online GD, some singularities emerged. First, patients with IGD were younger, more likely single and unemployed, and they also presented lower age of disorder onset. In addition, they displayed lower somatization and depressive scores together with lower prevalence of tobacco use but higher FA scores and higher mean body mass index. Finally, they presented lower novelty seeking and persistence traits. Discussion GD is fully recognized as a behavioral addiction, but IGD has been included in the Appendix of DSM-5 as a behavioral addiction that needs further study. Our findings suggest that IGD and online GD patients share some emotional distress and personality traits, but patients with IGD also display some differential characteristics, namely younger age, lower novelty seeking scores and higher BMI, and FA scores. Conclusions IGD presents some characteristics that are not extensive to online GD. These specificities have potential clinical implications and they need to be further studied.

Novel Variations of FANCA Gene Provokes Fanconi Anemia: Molecular Diagnosis in a Special Chinese Family.

PubMed

Li, Niu; Song, Aiyun; Ding, Lixia; Zhu, Hua; Li, Guoqiang; Miao, Yan; Wang, Jian; Li, Benshang; Chen, Jing

2018-07-01

Fanconi anemia (FA) is a rare autosomal recessive or X-linked disorder with highly variable clinical manifestations and an incidence of ∼1 to 5 in 1 million births. To date, 15 bona fide FA genes have been reported to be responsible for the known FA complementation groups and the FANCA gene accounts for almost 60%. In the present study, we report a special Chinese family, which has 2 children with classic FA characteristics. Via 2-step analysis of the whole-exome sequencing data and verification using multiplex ligation-dependent probe amplification test, one child was found to have a novel compound heterozygous mutation of a splicing variant (c.1471-1G>A) and a large intragenic deletion (exons 23-30 del) of the FANCA gene. The other child had the same splicing variant and another novel large deletion (exons 1-18 del) in the FANCA gene. Clone sequencing showed the c.1471-1G>A variant generate an altered transcript with 1 cryptic splice site in intron 15, resulting in a premature termination codon (p.Val490HisfsX6). This study not only shows the complexity of FA molecular diagnosis via comprehensively studying the FA pathogenic genes and the mutational spectrum, but also has significant reference value for the future molecular diagnosis of FA.

IL-6, IL-8, MMP-2, MMP-9 are overexpressed in Fanconi anemia cells through a NF-κB/TNF-α dependent mechanism.

PubMed

Epanchintsev, Alexey; Shyamsunder, Pavithra; Verma, Rama S; Lyakhovich, Alex

2015-12-01

Fanconi anemia (FA) is a rare autosomal recessive genetic disorder associated with a bone-marrow failure, genome instability, hypersensitivity to DNA crosslinking agents and a predisposition to cancer. Mutations have been documented in 16 FA genes that participate in the FA-BRCA DNA repair pathway, a fundamental pathway in the development of the disease and the presentation of its symptoms. FA cells have been characterized by an overproduction of cytokines, MAPKs, and Interleukins. Through this study we have identified the overexpression of additional secretory factors such as IL-6, IL-8, MMP-2, and MMP-9 in FA cells and in cells depleted of FANCA or FANCC and proved that their expression is under the control of NF-κB/TNF-α signaling pathways. We also demonstrated that these overexpressed secretory factors were effective in promoting the proliferation, migration, and invasion of surrounding tumor cells a fundamental event in the process of epithelial mesenchymal transition (EMT) and that they also modulated the expression of EMT markers such as E-cadherin and SNAIL. Overall our data suggest that the upregulation of EMT promoting factors in FA may contribute to predisposing FA patients to cancer, thereby providing new insights into possible therapeutic interventions. © 2014 Wiley Periodicals, Inc.

Fatty acid metabolism in the liver, measured by positron emission tomography, is increased in obese individuals.

PubMed

Iozzo, Patricia; Bucci, Marco; Roivainen, Anne; Någren, Kjell; Järvisalo, Mikko J; Kiss, Jan; Guiducci, Letizia; Fielding, Barbara; Naum, Alexandru G; Borra, Ronald; Virtanen, Kirsi; Savunen, Timo; Salvadori, Piero A; Ferrannini, Ele; Knuuti, Juhani; Nuutila, Pirjo

2010-09-01

Hepatic lipotoxicity results from and contributes to obesity-related disorders. It is a challenge to study human metabolism of fatty acids (FAs) in the liver. We combined (11)C-palmitate imaging by positron emission tomography (PET) with compartmental modeling to determine rates of hepatic FA uptake, oxidation, and storage, as well as triglyceride release in pigs and human beings. Anesthetized pigs underwent (11)C-palmitate PET imaging during fasting (n = 3) or euglycemic hyperinsulinemia (n = 3). Metabolic products of FAs were measured in arterial, portal, and hepatic venous blood. The imaging methodology then was tested in 15 human subjects (8 obese subjects); plasma (11)C-palmitate kinetic analyses were used to quantify systemic and visceral lipolysis. In pigs, PET-derived and corresponding measured FA fluxes (FA uptake, esterification, and triglyceride FA release) did not differ and were correlated with each other. In human beings, obese subjects had increased hepatic FA oxidation compared with controls (mean +/- standard error of the mean, 0.16 +/- 0.01 vs 0.08 +/- 0.01 micromol/min/mL; P = .0007); FA uptake and esterification rates did not differ between obese subjects and controls. Liver FA oxidation correlated with plasma insulin levels (r = 0.61, P = .016), adipose tissue (r = 0.58, P = .024), and systemic insulin resistance (r = 0.62, P = .015). Hepatic FA esterification correlated with the systemic release of FA into plasma (r = 0.71, P = .003). PET imaging can be used to measure FA metabolism in the liver. By using this technology, we found that obese individuals have increased hepatic oxidation of FA, in the context of adipose tissue insulin resistance, and increased FA flux from visceral fat. FA flux from visceral fat is proportional with the mass of the corresponding depot. Copyright © 2010 AGA Institute. Published by Elsevier Inc. All rights reserved.

Human Corneal Limbal-Epithelial Cell Response to Varying Silk Film Geometric Topography In Vitro

PubMed Central

Lawrence, Brian D.; Pan, Zhi; Liu, Aihong; Kaplan, David L.; Rosenblatt, Mark I.

2012-01-01

Silk fibroin films are a promising class of biomaterials that have a number of advantages for use in ophthalmic applications due to their transparent nature, mechanical properties and minimal inflammatory response upon implantation. Freestanding silk films with parallel line and concentric ring topographies were generated for in vitro characterization of human corneal limbal-epithelial (HCLE) cell response upon differing geometric patterned surfaces. Results indicated that silk film topography significantly affected initial HCLE culture substrate attachment, cellular alignment, cell-to-cell contact formation, actin cytoskeleton alignment, and focal adhesion (FA) localization. Most notably, parallel line patterned surfaces displayed a 36%–54% increase on average in initial cell attachment, which corresponded to an over 2-fold increase in FA localization when compared to other silk film surfaces and controls. In addition, distinct localization of FA formation was observed along the edges for all patterned silk film topographies. In conclusion, silk film feature topography appears to help direct corneal epithelial cell response and cytoskeleton development, especially in regards to FA distribution, in vitro. PMID:22705042

Evaluating the diagnostic utility of applying a machine learning algorithm to diffusion tensor MRI measures in individuals with major depressive disorder.

PubMed

Schnyer, David M; Clasen, Peter C; Gonzalez, Christopher; Beevers, Christopher G

2017-06-30

Using MRI to diagnose mental disorders has been a long-term goal. Despite this, the vast majority of prior neuroimaging work has been descriptive rather than predictive. The current study applies support vector machine (SVM) learning to MRI measures of brain white matter to classify adults with Major Depressive Disorder (MDD) and healthy controls. In a precisely matched group of individuals with MDD (n =25) and healthy controls (n =25), SVM learning accurately (74%) classified patients and controls across a brain map of white matter fractional anisotropy values (FA). The study revealed three main findings: 1) SVM applied to DTI derived FA maps can accurately classify MDD vs. healthy controls; 2) prediction is strongest when only right hemisphere white matter is examined; and 3) removing FA values from a region identified by univariate contrast as significantly different between MDD and healthy controls does not change the SVM accuracy. These results indicate that SVM learning applied to neuroimaging data can classify the presence versus absence of MDD and that predictive information is distributed across brain networks rather than being highly localized. Finally, MDD group differences revealed through typical univariate contrasts do not necessarily reveal patterns that provide accurate predictive information. Copyright © 2017 Elsevier Ireland Ltd. All rights reserved.

A critical evaluation of fasted state simulating gastric fluid (FaSSGF) that contains sodium lauryl sulfate and proposal of a modified recipe.

PubMed

Aburub, Aktham; Risley, Donald S; Mishra, Dinesh

2008-01-22

The aim of this work is to evaluate one of the most commonly used fasted state simulating gastric fluids (FaSSGFs), which contains sodium lauryl sulfate (SLS) (FaSSGF(SLS)), and propose a more appropriate surfactant concentration. Surface tension studies clearly show that the critical micelle concentration (CMC) of SLS in the relevant media (a media whose pH and sodium chloride concentration are representative of physiological conditions) is significantly lower (p<0.05) than 8.67 mM, which is the SLS concentration in FaSSGF(SLS). The CMC of SLS in the relevant media was determined to be 1.75 mM. Based on this a modified recipe is proposed in which the concentration of SLS is sufficient to achieve a surface tension similar to that in vivo without causing artificial micellar solubilization. Solubility, intrinsic dissolution, and GastroPlus modeling studies are presented to support and give rationale for the modified recipe. In addition, a comparison between the modified recipe and other FaSSGFs reported in the literature is made.

Diffusion tensor imaging of cingulum bundle and corpus callosum in schizophrenia vs. bipolar disorder.

PubMed

Nenadić, Igor; Hoof, Anna; Dietzek, Maren; Langbein, Kerstin; Reichenbach, Jürgen R; Sauer, Heinrich; Güllmar, Daniel

2017-08-30

Both schizophrenia and bipolar disorder show abnormalities of white matter, as seen in diffusion tensor imaging (DTI) analyses of major brain fibre bundles. While studies in each of the two conditions have indicated possible overlap in anatomical location, there are few direct comparisons between the disorders. Also, it is unclear whether phenotypically similar subgroups (e.g. patients with bipolar disorder and psychotic features) might share white matter pathologies or be rather similar. Using region-of-interest (ROI) analysis of white matter with diffusion tensor imaging (DTI) at 3 T, we analysed fractional anisotropy (FA), radial diffusivity (RD), and apparent diffusion coefficient (ADC) of the corpus callosum and cingulum bundle in 33 schizophrenia patients, 17 euthymic (previously psychotic) bipolar disorder patients, and 36 healthy controls. ANOVA analysis showed significant main effects of group for RD and ADC (both elevated in schizophrenia). Across the corpus callosum ROIs, there was not group effect on FA, but for RD (elevated in schizophrenia, lower in bipolar disorder) and ADC (higher in schizophrenia, intermediate in bipolar disorder). Our findings show similarities and difference (some gradual) across regions of the two major fibre tracts implicated in these disorders, which would be consistent with a neurobiological overlap of similar clinical phenotypes. Copyright © 2017 Elsevier Ireland Ltd. All rights reserved.

Impaired empathic abilities and reduced white matter integrity in schizophrenia.

PubMed

Fujino, Junya; Takahashi, Hidehiko; Miyata, Jun; Sugihara, Genichi; Kubota, Manabu; Sasamoto, Akihiko; Fujiwara, Hironobu; Aso, Toshihiko; Fukuyama, Hidenao; Murai, Toshiya

2014-01-03

Empathic abilities are impaired in schizophrenia. Although the pathology of schizophrenia is thought to involve disrupted white matter integrity, the relationship between empathic disabilities and altered white matter in the disorder remains unclear. The present study tested associations between empathic disabilities and white matter integrity in order to investigate the neural basis of impaired empathy in schizophrenia. Sixty-nine patients with schizophrenia and 69 age-, gender-, handedness-, education- and IQ level-matched healthy controls underwent diffusion-weighted imaging. Empathic abilities were assessed using the Interpersonal Reactivity Index (IRI). Using tract-based spatial statistics (TBSS), the associations between empathic abilities and white matter fractional anisotropy (FA), a measure of white matter integrity, were examined in the patient group within brain areas that showed a significant FA reduction compared with the controls. The patients with schizophrenia reported lower perspective taking and higher personal distress according to the IRI. The patients showed a significant FA reduction in bilateral deep white matter in the frontal, temporal, parietal and occipital lobes, a large portion of the corpus callosum, and the corona radiata. In schizophrenia patients, fantasy subscales positively correlated with FA in the left inferior fronto-occipital fasciculi and anterior thalamic radiation, and personal distress subscales negatively correlated with FA in the splenium of the corpus callosum. These results suggest that disrupted white matter integrity in these regions constitutes a pathology underpinning specific components of empathic disabilities in schizophrenia, highlighting that different aspects of empathic impairments in the disorder would have, at least partially, distinct neuropathological bases. © 2013.

Deviant white matter structure in adults with attention-deficit/hyperactivity disorder points to aberrant myelination and affects neuropsychological performance.

PubMed

Onnink, A Marten H; Zwiers, Marcel P; Hoogman, Martine; Mostert, Jeanette C; Dammers, Janneke; Kan, Cornelis C; Vasquez, Alejandro Arias; Schene, Aart H; Buitelaar, Jan; Franke, Barbara

2015-12-03

Attention-deficit/hyperactivity disorder (ADHD) in childhood is characterized by gray and white matter abnormalities in several brain areas. Considerably less is known about white matter microstructure in adults with ADHD and its relation with clinical symptoms and cognitive performance. In 107 adult ADHD patients and 109 gender-, age- and IQ-matched controls, we used diffusion tensor imaging (DTI) with tract-based spatial statistics (TBSS) to investigate whole-skeleton changes of fractional anisotropy (FA) and mean, axial, and radial diffusivity (MD, AD, RD). Additionally, we studied the relation of FA and MD values with symptom severity and cognitive performance on tasks measuring working memory, attention, inhibition, and delay discounting. In comparison to controls, participants with ADHD showed reduced FA in corpus callosum, bilateral corona radiata, and thalamic radiation. Higher MD and RD were found in overlapping and even more widespread areas in both hemispheres, also encompassing internal and external capsule, sagittal stratum, fornix, and superior lateral fasciculus. Values of FA and MD were not associated with symptom severity. However, within some white matter clusters that distinguished patients from controls, worse inhibition performance was associated with reduced FA and more impulsive decision making was associated with increased MD. This study shows widespread differences in white matter integrity between adults with persistent ADHD and healthy individuals. Changes in RD suggest aberrant myelination as a pathophysiological factor in persistent ADHD. The microstructural differences in adult ADHD may contribute to poor inhibition and greater impulsivity but appear to be independent of disease severity. Copyright © 2015. Published by Elsevier Inc.

Atypical Frontal-Striatal-Thalamic Circuit White Matter Development in Pediatric Obsessive Compulsive Disorder

PubMed Central

Fitzgerald, Kate D.; Liu, Yanni; Reamer, Elyse N.; Taylor, Stephan F.; Welsh, Robert C.

2015-01-01

Objective Atypical development of frontal-striatal-thalamic circuitry (FSTC) has been hypothesized to underlie the early course of obsessive-compulsive disorder (OCD); however, the development of FSTC white matter tracts remains to be studied in young patients. Method To address this gap, we scanned 36 patients with pediatric OCD compared to 27 healthy controls, aged 8 to 19 years, with diffusion tensor imaging (DTI) to measure fractional anisotropy (FA), an index of white matter coherence. Tract-based spatial statistics (TBSS) were used to test differential effects of age on FA, across the whole brain, in those with OCD compared to healthy youth, followed by analyses in a priori regions of interest (anterior corpus callosum, anterior cingulum bundle and anterior limb of the internal capsule [ALIC]) to further characterize developmental differences between groups. Results Patients with OCD showed more pronounced age-related increases in FA than controls in regions of interest, as well as several other white matter tracts. In patients, greater FA in anterior cingulum bundle correlated with more severe symptoms after controlling for age. Conclusions Our findings support theories of atypical FSTC maturation in pediatric OCD by providing the first evidence for altered trajectories of white matter development in anterior corpus callosum, anterior cingulum bundle, and ALIC in young patients. Steeper age-related increases of FA in these and other select white matter tracts in OCD, compared to healthy controls, may derive from an early delay in white matter development and/or prolonged white matter growth, but confirmation of these possibilities awaits longitudinal work. PMID:25440312

A Systematic Review of the Application And Correlates of YFAS-Diagnosed ‘Food Addiction’ in Humans: Are Eating-Related ‘Addictions’ a Cause for Concern or Empty Concepts?

PubMed Central

Long, Cecilia G.; Blundell, John E.; Finlayson, Graham

2015-01-01

The proposition of so-called ‘food addiction’ (FA) in the scientific literature has stimulated a recent surge in research and debate. The concept of FA is controversial, and opinion is divided. Many of the findings depend upon the use of a single instrument called the Yale Food Addiction Scale (YFAS). This review systematically examined FA, as defined by the YFAS, reported in 40 experimental human studies published in or after 2009. The results indicated that much of the literature makes the supposition that food addiction is an accepted neurobiological disease, consistent with substance use disorders; an interpretation based on very limited data. This raises the question as to whether those individuals who meet the YFAS criteria for diagnosis are truly ‘addicted’ to food or if they experience significant impairment to their psychological wellbeing and quality of life as would be expected in clinically recognised addictive disorders. At the present time, little research has investigated the extent to which a psychometric self-assessment of FA symptomatology can elucidate a harmful relationship with target foods in the diet. A positive YFAS diagnosis is usually positively associated with BMI and strongly linked with the presence of binge eating, but certain exceptions within the literature were revealed. Further clarification is required as to whether so-called FA is sufficiently different to existing conditions and traits to warrant classification as a distinctive disease phenotype rather than an expression of strong habits and preferences. PMID:26633647

A Systematic Review of the Application And Correlates of YFAS-Diagnosed 'Food Addiction' in Humans: Are Eating-Related 'Addictions' a Cause for Concern or Empty Concepts?

PubMed

Long, Cecilia G; Blundell, John E; Finlayson, Graham

2015-01-01

The proposition of so-called 'food addiction' (FA) in the scientific literature has stimulated a recent surge in research and debate. The concept of FA is controversial, and opinion is divided. Many of the findings depend upon the use of a single instrument called the Yale Food Addiction Scale (YFAS). This review systematically examined FA, as defined by the YFAS, reported in 40 experimental human studies published in or after 2009. The results indicated that much of the literature makes the supposition that food addiction is an accepted neurobiological disease, consistent with substance use disorders; an interpretation based on very limited data. This raises the question as to whether those individuals who meet the YFAS criteria for diagnosis are truly 'addicted' to food or if they experience significant impairment to their psychological wellbeing and quality of life as would be expected in clinically recognised addictive disorders. At the present time, little research has investigated the extent to which a psychometric self-assessment of FA symptomatology can elucidate a harmful relationship with target foods in the diet. A positive YFAS diagnosis is usually positively associated with BMI and strongly linked with the presence of binge eating, but certain exceptions within the literature were revealed. Further clarification is required as to whether so-called FA is sufficiently different to existing conditions and traits to warrant classification as a distinctive disease phenotype rather than an expression of strong habits and preferences. © 2015 S. Karger GmbH, Freiburg.

What can the Samoan "Fa'afafine" teach us about the Western concept of gender identity disorder in childhood?

PubMed

Vasey, Paul L; Bartlett, Nancy H

2007-01-01

This article examines whether gender identity disorder in childhood (GIDC) constitutes a mental disorder as outlined by the Diagnostic and Statistical Manual of Mental Disorders, 4th edition (DSM-IV-TR). Data were collected in Samoa, a culture that is characterized by a high degree of social tolerance towards feminine males who are known locally as fa'afafine. The study location was chosen because, unlike Western locales, it afforded the opportunity to examine whether gender-atypical behavior, gender-atypical identity, and sex-atypical identity, in and of themselves, cause distress in sex/gender variant individuals, while simultaneously controlling for the confounding effects of extreme societal intolerance towards such individuals. Because of our focus on the DSM-IV-TR's diagnosis of GIDC, we were specifically interested in ascertaining whether adult fa'afafine recalled a strong and persistent cross-gender identification in childhood, a sense of inappropriateness in the male-typical gender role, a discomfort with their sex, or distress associated with any of the above. In addition, we sought to determine whether parental encouragement or discouragement of cross-gender behaviors influence feelings of distress in relation to the behaviors in question. Based on the cross-cultural information presented here, we conclude that the diagnostic category of GIDC should not occur in its current form in future editions of the DSM, as there is no compelling evidence that cross-gender behaviors or identities, in and of themselves, cause distress in the individual.

[Modifications in myocardial energy metabolism in diabetic patients

NASA Technical Reports Server (NTRS)

Grynberg, A.

2001-01-01

The capacity of cardiac myocyte to regulate ATP production to face any change in energy demand is a major determinant of cardiac function. Because FA is the main heart fuel (although the most expensive one in oxygen, and prompt to induce deleterious effects), this process is based on a balanced fatty acid (FA) metabolism. Several pathological situations are associated with an accumulation of FA or derivatives, or with an excessive b-oxidation. The diabetic cardiomyocyte is characterised by an over consumption of FA. The control of the FA/glucose balance clearly appears as a new strategy for cytoprotection, particularly in diabetes and requires a reduced FA contribution to ATP production. Cardiac myocytes can control FA mitochondrial entry, but display weak ability to control FA uptake, thus the fate of non beta-oxidized FA appear as a new impairment for the cell. Both the trigger and the regulation of cardiac contraction result from membrane activity, and the other major FA function in the myocardium is their role in membrane homeostasis, through the phospholipid synthesis and remodeling pathways. Sudden death, hypercatecholaminemia, diabetes and heart failure have been associated with an altered PUFA content in cardiac membranes. Experimental data suggest that the 2 metabolic pathways involved in membrane homeostasis may represent therapeutic targets for cytoprotection. The drugs that increase cardiac phospholipid turnover (trimetazidine, ranolazine,...) display anti-ischemic non hemodynamic effect. This effect is based on a redirection of FA utilization towards phospholipid synthesis, which decrease their availability for energy production. A nutritional approach gave also promising results. Besides its anti-arrhythmic effect, the dietary docosahexaenoic acid is able to reduce FA energy consumption and hence oxygen demand. The cardiac metabolic pathways involving FA should be considered as a whole, precariously balanced. The diabetic heart being characterised by a different metabolic "status" with similarities to that of myocardium in coronary disease. Diabetes and other chronic cardiac diseases share common FA metabolism disorders leading to an altered energy balance, a decrease in long chain polyunsaturated Fas, and altered FA profiles in cardiac membranes. These disturbances, however, do not represent independent therapeutic targets, and should be considered as a whole.

Disrupted Signaling through the Fanconi Anemia Pathway Leads to Dysfunctional Hematopoietic Stem Cell Biology: Underlying Mechanisms and Potential Therapeutic Strategies

PubMed Central

Geiselhart, Anja; Lier, Amelie; Walter, Dagmar; Milsom, Michael D.

2012-01-01

Fanconi anemia (FA) is the most common inherited bone marrow failure syndrome. FA patients suffer to varying degrees from a heterogeneous range of developmental defects and, in addition, have an increased likelihood of developing cancer. Almost all FA patients develop a severe, progressive bone marrow failure syndrome, which impacts upon the production of all hematopoietic lineages and, hence, is thought to be driven by a defect at the level of the hematopoietic stem cell (HSC). This hypothesis would also correlate with the very high incidence of MDS and AML that is observed in FA patients. In this paper, we discuss the evidence that supports the role of dysfunctional HSC biology in driving the etiology of the disease. Furthermore, we consider the different model systems currently available to study the biology of cells defective in the FA signaling pathway and how they are informative in terms of identifying the physiologic mediators of HSC depletion and dissecting their putative mechanism of action. Finally, we ask whether the insights gained using such disease models can be translated into potential novel therapeutic strategies for the treatment of the hematologic disorders in FA patients. PMID:22675615

Identification of novel target genes involved in Indian Fanconi anemia patients using microarray.

PubMed

Shyamsunder, Pavithra; Ganesh, Kripa S; Vidyasekar, Prasanna; Mohan, Sheila; Verma, Rama Shanker

2013-12-01

Fanconi anemia (FA) is a genetic disorder characterized by progressive bone marrow failure and a predisposition to cancers. Mutations have been documented in 15 FA genes that participate in the FA-BRCA DNA repair pathway, a fundamental pathway in the development of the disease and the presentation of its characteristic symptoms. Certain symptoms such as oxygen sensitivity, hematological abnormalities and impaired immunity suggest that FA proteins could participate in or independently control other pathways as well. In this study, we identified 9 DNA repair genes that were down regulated in a genome wide analysis of 6 Indian Fanconi anemia patients. Functional clustering of a total of 233 dysregulated genes identified key biological processes that included regulation of transcription, DNA repair, cell cycle and chromosomal organization. Microarray data revealed the down regulation of ATXN3, ARID4A and ETS-1, which were validated by RTPCR in a subsequent sample set of 9 Indian FA patients. Here we report for the first time a gene expression profile of Fanconi anemia patients from the Indian population and a pool of genes that might aid in the acquisition and progression of the FA phenotype. © 2013 Elsevier B.V. All rights reserved.

A combined behavioral and morphological study on the effects of fetal asphyxia on the nigrostriatal dopaminergic system in adult rats.

PubMed

Strackx, E; Van den Hove, D L A; Steinbusch, H P; Steinbusch, H W M; Vles, J S H; Blanco, C E; Gavilanes, A W D

2008-06-01

Fetal asphyxic insults in the brain are known to be associated with developmental neurological problems like neuromotor disorders. However, little is known about the long-term consequences of fetal asphyxia (FA). For that reason, the present study investigated the long-term effects of FA on motor behavior and dopaminergic circuitry. FA was induced at embryonic day 17 by 75-minute clamping of the uterine circulation. SHAM animals underwent the same procedure except for the clamping. This was followed by full-term vaginal delivery of animals in all groups (FA, SHAM and untreated controls). At 6 months, basal and amphetamine-induced locomotor activity was measured during open field testing. Brain sections were stained for tyrosine hydroxylase (TH) and glial fibrillary acidic protein (GFAP). TH-positive cells and GFAP-positive cells in substantia nigra pars compacta (SN(C)) and striatum were counted using design-based stereology. Moreover, TH-immunoreactivity in the striatum was assessed by grey value measurements. Behavioral analysis demonstrated that SHAM and FA showed less basal and amphetamine-induced activity than controls. Histochemically, FA decreased the number of TH-positive neurons in the SN(C) and lowered TH-positive in the striatum. Furthermore, more GFAP-positive cells were found in the SN(C) and striatum in FA than in either control and SHAM groups. Additionally, FA animals showed ventriculomegaly associated with smaller white matter as well as grey matter volumes. The data show that FA was associated with deficits in both dopamine-related motor behavior and biochemistry. These alterations were associated with nigrostriatal astrogliosis. The present study demonstrates the sensitivity of the dopaminergic system towards FA.

Diagnosis of Fanconi Anemia by Diepoxybutane Analysis

PubMed Central

Auerbach, Arleen D.

2015-01-01

Fanconi anemia (FA) is a genetically and phenotypically heterogeneous disorder characterized by congenital malformations, progressive bone marrow failure, and predisposition to cancer, particularly hematological malignancies and solid tumors of the head and neck. The main role of FA proteins is in the repair of DNA interstrand crosslinks (ICLs). FA results from pathogenic variants in at least 16 distinct genes, causing genomic instability. Although the highly variable phenotype makes accurate diagnosis on the basis of clinical manifestations difficult in some patients, diagnosis based on a profound sensitivity to DNA crosslinking agents can be used to identify the pre-anemia patient as well as patients with aplastic anemia or leukemia who may or may not have the physical stigmata associated with the syndrome. Diepoxybutane (DEB) analysis is the preferred test for FA because other agents have higher rates of false-positive and false-negative results. PMID:25827349

Towards a Molecular Understanding of the Fanconi Anemia Core Complex

PubMed Central

Hodson, Charlotte; Walden, Helen

2012-01-01

Fanconi Anemia (FA) is a genetic disorder characterized by the inability of patient cells to repair DNA damage caused by interstrand crosslinking agents. There are currently 14 verified FA genes, where mutation of any single gene prevents repair of DNA interstrand crosslinks (ICLs). The accumulation of ICL damage results in genome instability and patients having a high predisposition to cancers. The key event of the FA pathway is dependent on an eight-protein core complex (CC), required for the monoubiquitination of each member of the FANCD2-FANCI complex. Interestingly, the majority of patient mutations reside in the CC. The molecular mechanisms underlying the requirement for such a large complex to carry out a monoubiquitination event remain a mystery. This paper documents the extensive efforts of researchers so far to understand the molecular roles of the CC proteins with regard to its main function in the FA pathway, the monoubiquitination of FANCD2 and FANCI. PMID:22675617

DNA interstrand cross-link repair: understanding role of Fanconi anemia pathway and therapeutic implications.

PubMed

Shukla, Pallavi; Solanki, Avani; Ghosh, Kanjaksha; Vundinti, Babu Rao

2013-11-01

Interstrand cross-links (ICLs) are extremely toxic DNA lesions that prevent DNA double-helix separation due to the irreversible covalent linkage binding of some agents on DNA strands. Agents that induce these ICLs are thus widely used as chemotherapeutic drugs but may also lead to tumor growth. Fanconi anemia (FA) is a rare genetic disorder that leads to ICL sensitivity. This review provides update on current understanding of the role of FA proteins in repairing ICLs at various stages of cell cycle. We also discuss link between DNA cross-link genotoxicity caused by aldehydes in FA pathway. Besides this, we summarize various ICL agents that act as drugs to treat different types of tumors and highlight strategies for modulating ICL sensitivity for therapeutic interventions that may be helpful in controlling cancer and life-threatening disease, FA. © 2013 John Wiley & Sons A/S. Published by John Wiley & Sons Ltd.

Effect of soil humic and fulvic acids, pH and ionic strength on Th(IV) sorption to TiO2 nanoparticles.

PubMed

Tan, Xiaoli; Wang, Xiangke; Chen, Changlun; Sun, Aihua

2007-04-01

Thorium is considered as a chemical analog of other tetravalent actinides. Herein, the sorption of Th(IV) on TiO(2) in the presence or absence of soil fulvic acid (FA)/humic acid (HA) as a function of pH, ionic strength and FA/HA concentration has been studied by a batch method. The morphology was characterized by scanning electron microscopy (SEM). The results indicate that sorption of Th(IV) on TiO(2) increases from 0% to approximately 94% at pH 1 approximately 4, and then maintains level with increasing pH values. Both FA and HA have a positive effect on Th(IV) sorption at low pH values and the contribution of FA on Th(IV) sorption is rather higher than that of HA at pH<4. The sorption is weakly dependent on the concentration of KNO(3) in solution, but the cations K(+), Na(+) and Li(+) influence Th(IV) sorption more obviously. The batch results indicate that the inner sphere complex formation is formed at bare surfaces or FA/HA-bound TiO(2) particle surfaces. Results of SEM analysis show that the particle sizes of TiO(2), Th-TiO(2) and Th-HA-TiO(2) colloids are quite different. Surface complexation may be considered as the main sorption mechanism.

The electrooxidation mechanism of formic acid on platinum and on lead ad-atoms modified platinum studied with the kinetic isotope effect

NASA Astrophysics Data System (ADS)

Bełtowska-Brzezinska, M.; Łuczak, T.; Stelmach, J.; Holze, R.

2014-04-01

Kinetics and mechanism of formic acid (FA) oxidation on platinum and upd-lead ad-atoms modified platinum electrodes have been studied using unlabelled and deuterated compounds. Poisoning of the electrode surface by CO-like species was prevented by suppression of dissociative chemisorption of FA due to a fast competitive underpotential deposition of lead ad-atoms on the Pt surface from an acidic solution containing Pb2+ cations. Modification of the Pt electrode with upd lead induced a catalytic effect in the direct electrooxidation of physisorbed FA to CO2. With increasing degree of H/D substitution, the rate of this reaction decreased in the order: HCOOH > DCOOH ≥ HCOOD > DCOOD. HCOOH was oxidized 8.5-times faster on a Pt/Pb electrode than DCOOD. This primary kinetic isotope effect proves that the C-H- and O-H-bonds are simultaneously cleaved in the rate determining step. A secondary kinetic isotope effect was found in the dissociative chemisorption of FA in the hydrogen adsorption-desorption range on a bare Pt electrode after H/D exchange in the C-H bond, wherein the influence of deuterium substitution in the O-H group was negligibly small. Thus the C-H bond cleavage is accompanied by the C-OH and not the O-H bond split in the FA decomposition, producing CO-like species on the Pt surface sites.

DTI-measured white matter abnormalities in adolescents with Conduct Disorder

PubMed Central

Haney-Caron, Emily; Caprihan, Arvind; Stevens, Michael C.

2013-01-01

Emerging research suggests that antisocial behavior in youth is linked to abnormal brain white matter microstructure, but the extent of such anatomical connectivity abnormalities remain largely untested because previous Conduct Disorder (CD) studies typically have selectively focused on specific frontotemporal tracts. This study aimed to replicate and extend previous frontotemporal diffusion tensor imaging (DTI) findings to determine whether noncomorbid CD adolescents have white matter microstructural abnormalities in major white matter tracts across the whole brain. Seventeen CD-diagnosed adolescents recruited from the community were compared to a group of 24 non-CD youth which did not differ in average age (12–18) or gender proportion. Tract-based spatial statistics (TBSS) fractional anisotropy (FA), axial diffusivity (AD), and radial diffusivity (RD) measurements were compared between groups using FSL nonparametric two-sample t test, clusterwise whole-brain corrected, p<.05. CD FA and AD deficits were widespread, but unrelated to gender, verbal ability, or CD age of onset. CD adolescents had significantly lower FA and AD values in frontal lobe and temporal lobe regions, including frontal lobe anterior/superior corona radiata, and inferior longitudinal and fronto-occpital fasciculi passing through the temporal lobe. The magnitude of several CD FA deficits was associated with number of CD symptoms. Because AD, but not RD, differed between study groups, abnormalities of axonal microstructure in CD rather than myelination are suggested. This study provides evidence that adolescent antisocial disorder is linked to abnormal white matter microstructure in more than just the uncinate fasciulcus as identified in previous DTI studies, or frontotemporal brain structures as suggested by functional neuroimaging studies. Instead, neurobiological risk specific to antisociality in adolescence is linked to microstructural abnormality in numerous long-range white matter connections among many diverse different brain regions. PMID:24139595

DTI-based connectome analysis of adolescents with major depressive disorder reveals hypoconnectivity of the right caudate.

PubMed

Tymofiyeva, Olga; Connolly, Colm G; Ho, Tiffany C; Sacchet, Matthew D; Henje Blom, Eva; LeWinn, Kaja Z; Xu, Duan; Yang, Tony T

2017-01-01

Adolescence is a vulnerable period for the onset of major depressive disorder (MDD). While some studies have shown white matter alterations in adolescent MDD, there is still a gap in understanding how the brain is affected at a network level. We compared diffusion tensor imaging (DTI)-based brain networks in a cohort of 57 adolescents with MDD and 41 well-matched healthy controls who completed self-reports of depression symptoms and stressful life events. Using atlas-based brain regions as network nodes and tractography streamline count or mean fractional anisotropy (FA) as edge weights, we examined weighted local and global network properties and performed Network-Based Statistic (NBS) analysis. While there were no significant group differences in the global network properties, the FA-weighted node strength of the right caudate was significantly lower in depressed adolescents and correlated positively with age across both groups. The NBS analysis revealed a cluster of lower FA-based connectivity in depressed subjects centered on the right caudate, including connections to frontal gyri, insula, and anterior cingulate. Within this cluster, the most robust difference between groups was the connection between the right caudate and middle frontal gyrus. This connection showed a significant diagnosis by stress interaction and a negative correlation with total stress in depressed adolescents. Use of DTI-based tractography, one atlas-based parcellation, and FA values to characterize brain networks represent this study's limitations. Our results allowed us to suggest caudate-centric models of dysfunctional processes underlying adolescent depression, which might guide future studies and help better understand and treat this disorder. Copyright © 2016 Elsevier B.V. All rights reserved.

Modular Integration of Upconverting Nanocrystal-Dendrimer Composites for Folate Receptor-Specific NIR Imaging and Light-Triggered Drug Release.

PubMed

Wong, Pamela T; Chen, Dexin; Tang, Shengzhuang; Yanik, Sean; Payne, Michael; Mukherjee, Jhindan; Coulter, Alexa; Tang, Kenny; Tao, Ke; Sun, Kang; Baker, James R; Choi, Seok Ki

2015-12-02

Upconversion nanocrystals (UCNs) display near-infrared (NIR)-responsive photoluminescent properties for NIR imaging and drug delivery. The development of effective strategies for UCN integration with other complementary nanostructures for targeting and drug conjugation is highly desirable. This study reports on a core/shell-based theranostic system designed by UCN integration with a folate (FA)-conjugated dendrimer for tumor targeting and with photocaged doxorubicin as a cytotoxic agent. Two types of UCNs (NaYF4:Yb/Er (or Yb/Tm); diameter = ≈50 to 54 nm) are described, each displaying distinct emission properties upon NIR (980 nm) excitation. The UCNs are surface modified through covalent attachment of photocaged doxorubicin (ONB-Dox) and a multivalent FA-conjugated polyamidoamine (PAMAM) dendrimer G5(FA)6 to prepare UCN@(ONB-Dox)(G5FA). Surface plasmon resonance experiments performed with G5(FA)6 dendrimer alone show nanomolar binding avidity (KD = 5.9 × 10(-9) M) to the folate binding protein. This dendrimer binding corresponds with selective binding and uptake of UCN@(ONB-Dox)(G5FA) by FAR-positive KB carcinoma cells in vitro. Furthermore, UCN@(ONB-Dox)(G5FA) treatment of FAR(+) KB cells inhibits cell growth in a light dependent manner. These results validate the utility of modularly integrated UCN-dendrimer nanocomposites for cell type specific NIR imaging and light-controlled drug release, thus serving as a new theranostic system. © 2015 WILEY-VCH Verlag GmbH & Co. KGaA, Weinheim.

Nutritional enhancement of sheep meat fatty acid profile for human health and wellbeing.

PubMed

Chikwanha, Obert C; Vahmani, Payam; Muchenje, Voster; Dugan, Michael E R; Mapiye, Cletos

2018-02-01

Dietary fatty acids (FA) consumed by sheep, like other ruminants, can undergo biohydrogenation resulting in high proportions of saturated FA (SFA) in meat. Biohydrogenation is typically less extensive in sheep than cattle, and consequently, sheep meat can contain higher proportions of omega (n)-3 polyunsaturated FA (PUFA), and PUFA biohydrogenation intermediates (PUFA-BHI) including conjugated linoleic acid (CLA) and trans-monounsaturated FAs (t-MUFA). Sheep meat is also noted for having characteristically higher contents of branched chain FA (BCFA). From a human health and wellness perspective, some SFA and trans-MUFA have been found to negatively affect blood lipid profiles, and are associated with increased risk of cardiovascular disease (CVD). On the other hand, n-3 PUFA, BCFA and some PUFA-BHI may have many potential beneficial effects on human health and wellbeing. In particular, vaccenic acid (VA), rumenic acid (RA) and BCFA may have potential for protecting against cancer and inflammatory disorders among other human health benefits. Several innovative strategies have been evaluated for their potential to enrich sheep meat with FA which may have human health benefits. To this end, dietary manipulation has been found to be the most effective strategy of improving the FA profile of sheep meat. However, there is a missing link between the FA profile of sheep meat, human consumption patterns of sheep FA and chronic diseases. The current review provides an overview of the nutritional strategies used to enhance the FA profile of sheep meat for human consumption. Copyright © 2017 Elsevier Ltd. All rights reserved.

Increased red cell distribution width in Fanconi anemia: a novel marker of stress erythropoiesis.

PubMed

Sousa, Rosa; Gonçalves, Cristina; Guerra, Isabel Couto; Costa, Emília; Fernandes, Ana; do Bom Sucesso, Maria; Azevedo, Joana; Rodriguez, Alfredo; Rius, Rocio; Seabra, Carlos; Ferreira, Fátima; Ribeiro, Letícia; Ferrão, Anabela; Castedo, Sérgio; Cleto, Esmeralda; Coutinho, Jorge; Carvalho, Félix; Barbot, José; Porto, Beatriz

2016-07-25

Red cell distribution width (RDW), a classical parameter used in the differential diagnosis of anemia, has recently been recognized as a marker of chronic inflammation and high levels of oxidative stress (OS). Fanconi anemia (FA) is a genetic disorder associated to redox imbalance and dysfunctional response to OS. Clinically, it is characterized by progressive bone marrow failure, which remains the primary cause of morbidity and mortality. Macrocytosis and increased fetal hemoglobin, two indicators of bone marrow stress erythropoiesis, are generally the first hematological manifestations to appear in FA. However, the significance of RDW and its possible relation to stress erythropoiesis have never been explored in FA. In the present study we analyzed routine complete blood counts from 34 FA patients and evaluated RDW, correlating with the hematological parameters most consistently associated with the FA phenotype. We showed, for the first time, that RDW is significantly increased in FA. We also showed that increased RDW is correlated with thrombocytopenia, neutropenia and, most importantly, highly correlated with anemia. Analyzing sequential hemograms from 3 FA patients with different clinical outcomes, during 10 years follow-up, we confirmed a consistent association between increased RDW and decreased hemoglobin, which supports the postulated importance of RDW in the evaluation of hematological disease progression. This study shows, for the first time, that RDW is significantly increased in FA, and this increment is correlated with neutropenia, thrombocytopenia, and highly correlated with anemia. According to the present results, it is suggested that increased RDW can be a novel marker of stress erythropoiesis in FA.

A cross-sectional study of insight and family accommodation in pediatric obsessive-compulsive disorder

PubMed Central

2013-01-01

Background Factors predicting treatment outcome in pediatric patients with obsessive-compulsive disorder (OCD) include disease severity, functional impairment, comorbid disorders, insight, and family accommodation (FA). Treatment of pediatric OCD is often only partly successful as some of these predictors are not targeted with conventional therapy. Among these, insight and FA were identified to be modifiable predictors of special relevance to pediatric OCD. Despite their clinical relevance, insight and FA remain understudied in youth with OCD. This study examined the clinical correlates of insight and FA and determined whether FA mediates the relationship between symptom severity and functional impairment in pediatric OCD. Methods This was a cross-sectional, outpatient study. Thirty-five treatment-naive children and adolescentswith DSM-IV diagnosis of OCD (mean age: 13.11 ± 3.16; 54.3% males) were included. Standard questionnaires were administered for assessing the study variables. Insight and comorbidities were assessed based on clinician’s interview. Subjects were categorized as belonging to a high insight or a low insight group, and the differences between these two groups were analyzed using ANOVA. Pearson’s correlation coefficients were calculated for the remaining variables of interest. Mediation analysis was carried out using structural equation modeling. Results Relative to those in the high insight group, subjects in the low insight group were younger, had more severe disease and symptoms, and were accommodated to a greater extent by their families. In addition, comorbid depression was more frequent in subjects belonging to the low insight group. Family accommodation was positively related to disease severity, symptom severity, and functional impairment. Family accommodation totally mediated the relationship between symptom severity and functional impairment. Conclusions Results support the differences in the diagnostic criteria between adult and pediatric patients with OCD with respect to the requirement of insight. Subjects with low insight displayed clinical characteristics of increased severity compared with their high insight counterparts, suggesting that subjects with low insight may require multimodal approach to treatment. Family accommodation was found to mediate the relationship between symptom severity and functional impairment; the use of family-based approaches to cognitive behavioral therapy, with one of the aims of reducing/mitigating FA, may provide better treatment outcomes in pediatric OCD. PMID:23786761

ANTS-anchored Zn-Al-CO3-LDH particles as fluorescent probe for sensing of folic acid

NASA Astrophysics Data System (ADS)

Liu, Pengfei; Liu, Dan; Liu, Yanhuan; Li, Lei

2016-09-01

A novel fluorescent nanosensor for detecting folic acid (FA) in aqueous media has been developed based on 8-aminonaphthalene-1,3,6-trisulfonate (ANTS) anchored to the surface of Zn-Al-CO3-layered double hydroxides (LDH) particles. The nanosensor showed high fluorescence intensity and good photostability due to a strong coordination interaction between surface Zn2+ ions of Zn-Al-CO3-LDH and N atoms of ANTS, which were verified by result of X-ray photoelectron spectroscopy (XPS). ANTS-anchored on the surface of Zn-Al-CO3-LDH restricted the intra-molecular rotation leading to ANTS-anchored J-type aggregation emission enhancement. ANTS-anchored Zn-Al-CO3-LDH particles exhibited highly sensitive and selective response to FA over other common metal ions and saccharides present in biological fluids. The proposed mechanism was that oxygen atoms of -SO3 groups in ANTS-anchored on the surface of Zn-Al-CO3-LDH were easily collided by FA molecules to form potential hydrogen bonds between ANTS-anchored and FA molecules, which could effectively quench the ANTS-anchored fluorescence. Under the simulated physiological conditions (pH of 7.4), the fluorescence quenching was fitted to Stern-Volmer equation with a linear response in the concentration range of 1 μM to 200 μM with a limit of detection of 0.1 μM. The results indicate that ANTS-anchored Zn-Al-CO3-LDH particles can afford a very sensitive system for the sensing FA in aqueous solution.

Novel signature fatty acid profile of the giant manta ray suggests reliance on an uncharacterised mesopelagic food source low in polyunsaturated fatty acids

PubMed Central

Guerrero, Michel; Marshall, Andrea D.; Richardson, Anthony J.; Bennett, Mike B.; Couturier, Lydie I. E.

2018-01-01

Traditionally, large planktivorous elasmobranchs have been thought to predominantly feed on surface zooplankton during daytime hours. However, the recent application of molecular methods to examine long-term assimilated diets, has revealed that these species likely gain the majority from deeper or demersal sources. Signature fatty acid analysis (FA) of muscle tissue was used to examine the assimilated diet of the giant manta ray Mobula birostris, and then compared with surface zooplankton that was collected during feeding and non-feeding events at two aggregation sites off mainland Ecuador. The FA profiles of M. birostris and surface zooplankton were markedly different apart from similar proportions of arachidonic acid, which suggests daytime surface zooplankton may comprise a small amount of dietary intake for M. birostris. The FA profile of M. birostris muscle was found to be depleted in polyunsaturated fatty acids, and instead comprised high proportions of 18:1ω9 isomers. While 18:1ω9 isomers are not explicitly considered dietary FAs, they are commonly found in high proportions in deep-sea organisms, including elasmobranch species. Overall, the FA profile of M. birostris suggests a diet that is mesopelagic in origin, but many mesopelagic zooplankton species also vertically migrate, staying deep during the day and moving to shallower waters at night. Here, signature FA analysis is unable to resolve the depth at which these putative dietary items were consumed and how availability of this prey may drive distribution and movements of this large filter-feeder. PMID:29329295

Novel signature fatty acid profile of the giant manta ray suggests reliance on an uncharacterised mesopelagic food source low in polyunsaturated fatty acids.

PubMed

Burgess, Katherine B; Guerrero, Michel; Marshall, Andrea D; Richardson, Anthony J; Bennett, Mike B; Couturier, Lydie I E

2018-01-01

Traditionally, large planktivorous elasmobranchs have been thought to predominantly feed on surface zooplankton during daytime hours. However, the recent application of molecular methods to examine long-term assimilated diets, has revealed that these species likely gain the majority from deeper or demersal sources. Signature fatty acid analysis (FA) of muscle tissue was used to examine the assimilated diet of the giant manta ray Mobula birostris, and then compared with surface zooplankton that was collected during feeding and non-feeding events at two aggregation sites off mainland Ecuador. The FA profiles of M. birostris and surface zooplankton were markedly different apart from similar proportions of arachidonic acid, which suggests daytime surface zooplankton may comprise a small amount of dietary intake for M. birostris. The FA profile of M. birostris muscle was found to be depleted in polyunsaturated fatty acids, and instead comprised high proportions of 18:1ω9 isomers. While 18:1ω9 isomers are not explicitly considered dietary FAs, they are commonly found in high proportions in deep-sea organisms, including elasmobranch species. Overall, the FA profile of M. birostris suggests a diet that is mesopelagic in origin, but many mesopelagic zooplankton species also vertically migrate, staying deep during the day and moving to shallower waters at night. Here, signature FA analysis is unable to resolve the depth at which these putative dietary items were consumed and how availability of this prey may drive distribution and movements of this large filter-feeder.

Snm1B/Apollo functions in the Fanconi anemia pathway in response to DNA interstrand crosslinks.

PubMed

Mason, Jennifer M; Sekiguchi, JoAnn M

2011-07-01

Fanconi anemia (FA) is an inherited chromosomal instability disorder characterized by childhood aplastic anemia, developmental abnormalities and cancer predisposition. One of the hallmark phenotypes of FA is cellular hypersensitivity to agents that induce DNA interstrand crosslinks (ICLs), such as mitomycin C (MMC). FA is caused by mutation in at least 14 genes which function in the resolution of ICLs during replication. The FA proteins act within the context of a protein network in coordination with multiple repair factors that function in distinct pathways. SNM1B/Apollo is a member of metallo-β-lactamase/βCASP family of nucleases and has been demonstrated to function in ICL repair. However, the relationship between SNM1B and the FA protein network is not known. In the current study, we establish that SNM1B functions epistatically to the central FA factor, FANCD2, in cellular survival after ICL damage and homology-directed repair of DNA double-strand breaks. We also demonstrate that MMC-induced chromosomal anomalies are increased in SNM1B-depleted cells, and this phenotype is not further exacerbated upon depletion of either FANCD2 or another key FA protein, FANCI. Furthermore, we find that SNM1B is required for proper localization of critical repair factors, including FANCD2, BRCA1 and RAD51, to MMC-induced subnuclear foci. Our findings demonstrate that SNM1B functions within the FA pathway during the repair of ICL damage.

Structural abnormality of the corticospinal tract in major depressive disorder

PubMed Central

2014-01-01

Background Scientists are beginning to document abnormalities in white matter connectivity in major depressive disorder (MDD). Recent developments in diffusion-weighted image analyses, including tractography clustering methods, may yield improved characterization of these white matter abnormalities in MDD. In this study, we acquired diffusion-weighted imaging data from MDD participants and matched healthy controls. We analyzed these data using two tractography clustering methods: automated fiber quantification (AFQ) and the maximum density path (MDP) procedure. We used AFQ to compare fractional anisotropy (FA; an index of water diffusion) in these two groups across major white matter tracts. Subsequently, we used the MDP procedure to compare FA differences in fiber paths related to the abnormalities in major fiber tracts that were identified using AFQ. Results FA was higher in the bilateral corticospinal tracts (CSTs) in MDD (p’s < 0.002). Secondary analyses using the MDP procedure detected primarily increases in FA in the CST-related fiber paths of the bilateral posterior limbs of the internal capsule, right superior corona radiata, and the left external capsule. Conclusions This is the first study to implicate the CST and several related fiber pathways in MDD. These findings suggest important new hypotheses regarding the role of CST abnormalities in MDD, including in relation to explicating CST-related abnormalities to depressive symptoms and RDoC domains and constructs. PMID:25295159

Corpus callosum integrity is affected by mood disorders and also by the suicide attempt history: A diffusion tensor imaging study.

PubMed

Cyprien, Fabienne; de Champfleur, Nicolas Menjot; Deverdun, Jérémy; Olié, Emilie; Le Bars, Emmanuelle; Bonafé, Alain; Mura, Thibault; Jollant, Fabrice; Courtet, Philippe; Artero, Sylvaine

2016-12-01

Some MRI studies have noted alterations in the corpus callosum (CC) white matter integrity of individuals with mood disorders and also in patients with suicidal behavior. We investigated the specific impact of suicidal behavior on CC integrity in mood disorders. CC structural changes were assessed by diffusion tensor imaging (DTI) in 121 women 18-50-year-old): 41 with bipolar disorder (BD), 50 with major depressive disorder (MDD) and 30 healthy controls (HC). Fractional anisotropy (FA) and DTI metrics were calculated for the genu, body and splenium of CC and compared in the three groups by MANCOVA. Then, they were re-analyzed relative to the suicide attempt history within the MDD and BD groups and to the suicide number/severity. FA values for the CC genu and body were lower in non-suicide attempters with BD than with MDD and in HC. Conversely, FA values for all CC regions were significantly lower in suicide attempters with BD than in HC. Finally, higher number of suicide attempts (>2) and elevated Suicidal Intent Scale score were associated with significant splenium alterations. Limitations include the cross-sectional design (non-causal study), the potential influence of medications and concerns about the generalizability to men. Genu and body are altered in non-suicide attempters with BD, while splenium is specifically altered in suicide attempters, independently from their psychiatric status. History of suicide attempts may be a source of heterogeneity in the association between CC alterations and BD and may partially explain the variable results of previous studies. Copyright © 2016 Elsevier B.V. All rights reserved.

Sweat pore reactivity as a surrogate measure of sympathetic nervous system activity in trauma-exposed individuals with and without posttraumatic stress disorder.

PubMed

Familoni, Babajide O; Gregor, Kristin L; Dodson, Thomas S; Krzywicki, Alan T; Lowery, Bobby N; Orr, Scott P; Suvak, Michael K; Rasmusson, Ann M

2016-09-01

Stress analysis by FLIR (forward-looking infrared) evaluation (SAFE) has been demonstrated to monitor sweat pore activation (SPA) as a novel surrogate measure of sympathetic nervous system (SNS) activity in a normal population. SNS responses to a series of 15 1-s, 82 dB, white noise bursts were measured by skin conductance (SC) and SAFE monitoring of SPA on the fingers (FiP) and face (FaP) in 10 participants with posttraumatic stress disorder (PTSD) and 16 trauma-exposed participants without PTSD (Mage  = 48.92 ± 12.00 years; 26.9% female). Within participants, SC and FiP responses across trials were strongly correlated (r = .92, p < .001). Correlations between SC and FaP (r = .76, p = .001) and between FiP and FaP (r = .47, p = .005) were smaller. The habituation of SNS responses across the 15 trials was substantial (SC: d = -2.97; FiP: d = -2.34; FaP: d = -1.02). There was a strong correlation between habituation effects for SC and FiP (r = .76, p < .001), but not for SC and FaP (r = .15, p = .45) or FiP and FaP (r = .29, p = .16). Participants with PTSD showed larger SNS responses to the first loud noise than those without PTSD. PTSD reexperiencing symptoms assessed by the PTSD Checklist on the day of testing were associated with the SNS responses to the first loud noise measured by SC (d = 1.19) and FiP (d = .99), but not FaP (d = .10). This study confirms convergence of SAFE and SC as valid measures of SNS activity. SAFE FiP and SC responses were highly predictive of self-rated PTSD reexperiencing symptoms. SAFE may offer an attractive alternative for applications in PTSD and similar populations. © 2016 Society for Psychophysiological Research. This article has been contributed to by US Government employees and their work is in the public domain in the USA.

ANTS-anchored Zn-Al-CO{sub 3}-LDH particles as fluorescent probe for sensing of folic acid

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

Liu, Pengfei; Liu, Dan; Liu, Yanhuan

2016-09-15

A novel fluorescent nanosensor for detecting folic acid (FA) in aqueous media has been developed based on 8-aminonaphthalene-1,3,6-trisulfonate (ANTS) anchored to the surface of Zn-Al-CO{sub 3}-layered double hydroxides (LDH) particles. The nanosensor showed high fluorescence intensity and good photostability due to a strong coordination interaction between surface Zn{sup 2+} ions of Zn-Al-CO{sub 3}-LDH and N atoms of ANTS, which were verified by result of X-ray photoelectron spectroscopy (XPS). ANTS-anchored on the surface of Zn-Al-CO{sub 3}-LDH restricted the intra-molecular rotation leading to ANTS-anchored J-type aggregation emission enhancement. ANTS-anchored Zn-Al-CO{sub 3}-LDH particles exhibited highly sensitive and selective response to FA over othermore » common metal ions and saccharides present in biological fluids. The proposed mechanism was that oxygen atoms of -SO{sub 3} groups in ANTS-anchored on the surface of Zn-Al-CO{sub 3}-LDH were easily collided by FA molecules to form potential hydrogen bonds between ANTS-anchored and FA molecules, which could effectively quench the ANTS-anchored fluorescence. Under the simulated physiological conditions (pH of 7.4), the fluorescence quenching was fitted to Stern-Volmer equation with a linear response in the concentration range of 1 μM to 200 μM with a limit of detection of 0.1 μM. The results indicate that ANTS-anchored Zn-Al-CO{sub 3}-LDH particles can afford a very sensitive system for the sensing FA in aqueous solution. - Highlights: • A novel fluorescent nanosensor has been developed. • The sensor exhibited highly sensitive and selective response to FA. • The fluorescence quenching was fitted to Stern–Volmer equation. • The linear response range was 1–200 μM with a limit of detection of 0.1 μM.« less

Poorly crystalline hydroxyapatite: A novel adsorbent for enhanced fulvic acid removal from aqueous solution

NASA Astrophysics Data System (ADS)

Wei, Wei; Yang, Lei; Zhong, Wenhui; Cui, Jing; Wei, Zhenggui

2015-03-01

In this study, poorly crystalline hydroxyapatite (HAP) was developed as an efficient adsorbent for the removal of fulvic acid (FA) from aqueous solution. Surface functionality, crystallinity, and morphology of the synthetic adsorbent were studied by Fourier-transformation infrared (FT-IR) spectroscopy, powder X-ray diffraction (XRD) and transmission electron microscopy (TEM). The effects of various parameters such as crystallinity of adsorbent, contact time, adsorbent dosage, pH, initial adsorbate concentration, temperature, ionic strength and the presence of alkaline earth metal ions on FA adsorption were investigated. Results indicated that the nanosized HAP calcined at lower temperature was poorly crystalline (Xc = 0.23) and had better adsorption capacity for FA than those (Xc = 0.52, 0.86) calcined at higher temperature. FA removal was increased with increases of adsorbent dosage, temperature, ionic strength and the presence of alkali earth metal ions, but decreased as the pH increased. Kinetic studies showed that pseudo-second-order kinetic model better described the adsorption process. Equilibrium data were best described by Sips models, and the estimated maximum adsorption capacity of poorly crystalline HAP was 90.20 mg/g at 318 K, displaying higher efficiency for FA removal than previously reported adsorbents. FT-IR results revealed that FA adsorption over the adsorbent could be attributed to the surface complexation between the oxygen atom of functional groups of FA and calcium ions of HAP. Regeneration studies indicated that HAP could be recyclable for a long term. Findings of the present work highlight the potential for using poorly crystalline HAP nanoparticles as an effective and recyclable adsorbent for FA removal from aqueous solution.

Curcumin-guided nanotherapy: a lipid-based nanomedicine for targeted drug delivery in breast cancer therapy.

PubMed

Lin, Mingzhen; Teng, Lili; Wang, Yang; Zhang, Jiaxin; Sun, Xianglian

2016-05-01

Delivery of anti-cancer drugs into the cancer cells or tissues by multifunctional nanocarriers may provide a new paradigm in cancer treatment. In this study, folate (FA) decorated nanostructured lipid carriers (NLCs) were constructed as nanomedicine for the delivery of curcumin (CUR). CUR-loaded NLCs (CUR-NLCs) were prepared. FA containing polyethylene glycol (PEG)-distearoylphosphatidylethanolamine (DSPE) (FA-PEG-DSPE) was synthesized and used for the decoration of CUR-NLCs. Their particle size, zeta potential, and drug encapsulation efficiency (EE) were evaluated. In vitro cytotoxicity study FA decorated CUR-NLCs (FA-CUR-NLCs) was tested in MCF-7 human breast cancer cells (MCF-7 cells). In vivo anti-tumor efficacies of the carriers were evaluated on mice bearing breast cancer model. The optimum FA-CUR-NLCs formulations with the particle size of 127 nm and with a +13 mV surface charge. The growth of MCF-7 cells in vitro was obviously inhibited. FA-CUR-NLCs also displayed the best anti-tumor activity than other formulations in vivo. The results demonstrated that FA-CUR-NLCs were efficient in selective delivery to cancer cells over-expressing FA receptors (FRs). Also FA-CUR-NLCs transfer CUR to the breast cancer cells, enhance the anti-tumor capacity. Thus, FA-CUR-NLCs could prove to be a superior nanomedicine to achieve tumor therapeutic efficacy.

Organic matter in sediments of an acidic mining lake as assessed by lipid analysis. Part I: fatty acids.

PubMed

Poerschmann, Juergen; Koschorreck, Matthias; Górecki, Tadeusz

2012-01-01

Fatty acid (FA) patterns of sediments collected from the bottom of an acidic mine pit lake (AML) at different depths (surface sediment: 0 to 1cm; deep sediment: 4 to 5 cm) were studied to characterize microbial communities and the sources of sedimentary organic matter (SOM). Studies were performed on the molecular level utilizing source-specific, diagnostic FA biomarkers. The biomarker-based approach has been used widely in marine sediment studies, but has not been applied for sediments from AMLs so far. Combined FA concentrations in the surface sediment were higher compared to those in the deep sediment (497 vs. 127 μg g(-1)d.w., respectively). This was related to deposition of autochthonous biomass and higher terrestrial plants onto the surface sediment, as well as--to lesser extent--with higher bacterial activity on the sediment-water interface. The FA distribution in both sediments was characterized by a strong even-over-odd preference and was bimodal in nature: there was a cluster at nC(14)-nC(18) characteristic of chiefly autochthonous (algal and bacterial) SOM production, and another cluster at nC(22-28) related to input from higher plants. The FA distribution in the surface sediment pointed to higher terrestrial input compared to autochthonous contribution to SOM (67%:33%) as an estimate. Fingerprinting of viable bacteria was accomplished through signature FA markers including branched C(15) and C(17) surrogates, cyclopropanoic acids, 3-hydroxy (OH) acids and monounsaturated surrogates with unusual double bond localization. The abundance of Gram-negative bacteria was higher in the surface sediment as evidenced by total diagnostic 3-OH-fatty acids (37 μg g(-1) versus 25 μg g(-1)). Potential source taxa in both sediment layers included acidophilic iron- and sulfur-oxidizing bacteria including Acidithiobacillus ferrooxidans. High abundances of terminally branched C(15) and C(17) surrogates in both sediments pointed to sulfate- and iron-reducing bacteria. Signature FAs characteristic of methanotrophs were virtually lacking in both sediments. Copyright © 2011 Elsevier B.V. All rights reserved.

Adsorption of aquatic humic substances on colloidal-size aluminum oxide particles: Influence of solution chemistry

NASA Astrophysics Data System (ADS)

Schlautman, Mark A.; Morgan, James J.

1994-10-01

The adsorption of Suwannee River humic substances (HS) on colloidal-size aluminum oxide particles was examined as a function of solution chemistry. The amount of humic acid (HA) or fulvic acid (FA) adsorbed decreased with increasing pH for all solutions of constant ionic strength. In NaCl solutions at fixed pH values, the adsorption of HA and FA increased with increasing ionic strength. The presence of Ca 2+ enhanced the adsorption of HA but had little effect on FA. For identical solution conditions, the amount (by mass) of HA adsorbed to alumina was always greater than FA. Adsorption densities for both HA and FA showed good agreement with the Langmuir equation, and interpretations of adsorption processes were made from the model parameters. For FA, ligand exchange appears to be the dominant adsorption reaction for the conditions studied here. Ligand exchange is also a major adsorption reaction for HA; however, other reactions contribute to adsorption for some solution compositions. At high pH, cation and water bridging become increasingly important for HA adsorption with increasing amounts of Na + and Ca 2+, respectively. At low to neutral pH values, increases in these same two cations make hydrophobic bonding more effective. Calculations of HS carboxyl group densities in the adsorbed layer support the proposed adsorption reactions. From the adsorption data it appears that fewer than 3.3 HS-COO - groups per nm 2 can be bound directly as inner-sphere complexes by the alumina surface. We propose that the influence of aqueous chemistry on HS adsorption reactions, and therefore on the types of HS surface complexes formed, affects the formation and nature of organic coatings on mineral surfaces.

Structural and Diffusion Property Alterations in Unaffected Siblings of Patients with Obsessive-Compulsive Disorder

PubMed Central

Shi, Changzheng; Miao, Guodong; Yang, Qiong; Gao, Wei; Wolff, Jason J.; Chan, Raymond C. K.; Shen, Dinggang

2014-01-01

Disrupted white matter integrity and abnormal cortical thickness are widely reported in the pathophysiology of obsessive-compulsive disorder (OCD). However, the relationship between alterations in white matter connectivity and cortical thickness in OCD is unclear. In addition, the heritability of this relationship is poorly understood. To investigate the relationship of white matter microstructure with cortical thickness, we measure fractional anisotropy (FA) of white matter in 30 OCD patients, 19 unaffected siblings and 30 matched healthy controls. Then, we take those regions of significantly altered FA in OCD patients compared with healthy controls to perform fiber tracking. Next, we calculate the fiber quantity in the same tracts. Lastly, we compare cortical thickness in the target regions of those tracts. Patients with OCD exhibited decreased FA in cingulum, arcuate fibers near the superior parietal lobule, inferior longitudinal fasciculus near the right superior temporal gyrus and uncinate fasciculus. Siblings showed reduced FA in arcuate fibers near the superior parietal lobule and anterior limb of internal capsule. Significant reductions in both fiber quantities and cortical thickness in OCD patients and their unaffected siblings were also observed in the projected brain areas when using the arcuate fibers near the left superior parietal lobule as the starting points. Reduced FA in the left superior parietal lobule was observed not only in patients with OCD but also in their unaffected siblings. Originated from the superior parietal lobule, the number of fibers was also found to be decreased and the corresponding cortical regions were thinner relative to controls. The linkage between disrupted white matter integrity and the abnormal cortical thickness may be a vulnerability marker for OCD. PMID:24489665

Testing the hypothesis of accelerated cerebral white matter aging in schizophrenia and major depression.

PubMed

Kochunov, Peter; Glahn, David C; Rowland, Laura M; Olvera, Rene L; Winkler, Anderson; Yang, Yi-Hong; Sampath, Hemalatha; Carpenter, Will T; Duggirala, Ravindranath; Curran, Joanne; Blangero, John; Hong, L Elliot

2013-03-01

Elevated rate of aging-related biological and functional decline, termed "accelerated aging," is reported in patients with schizophrenia (SCZ) and major depressive disorder (MDD). We used diffusion tensor imaging derived fractional anisotropy (FA) as a biomarker of aging-related decline in white matter (WM) integrity to test the hypotheses of accelerated aging in SCZ and MDD. The SCZ cohort comprised 58 SCZ patients and 60 controls (aged 20-60 years). The MDD cohort comprised 136 MDD patients and 351 controls (aged 20-79 years). The main outcome measures were the diagnosis-by-age interaction on whole-brain-averaged WM FA values and FA values from 12 major WM tracts. Diagnosis-by-age interaction for the whole-brain average FA was significant for the SCZ (p = .04) but not the MDD (p = .80) cohort. Diagnosis-by-age interaction was nominally significant (p<.05) for five WM tracts for SCZ and for none of the tracts in the MDD cohort. Tract-specific heterochronicity of the onset of age-related decline in SCZ demonstrated strong negative correlations with the age-of-peak myelination and the rates of age-related decline obtained from normative sample (r =-.61 and-.80, p<.05, respectively). No such trends existed for MDD cohort. Cerebral WM showed accelerated aging in SCZ but not in MDD, suggesting some difference in the pathophysiology underlying their WM aging changes. Tract-specific heterochronicity of WM development modulated presentation of accelerated aging in SCZ: WM tracts that matured later in life appeared more sensitive to the pathophysiology of SCZ and demonstrated more susceptibility to disorder-related accelerated decline in FA values with age. This trend was not observed in MDD cohort. Copyright © 2013 Society of Biological Psychiatry. Published by Elsevier Inc. All rights reserved.

Testing the hypothesis of accelerated cerebral white matter aging in schizophrenia and major depression

PubMed Central

Kochunov, P.; Glahn, D.C.; Rowland, L.M.; Olvera, R.L.; Winkler, A; Yang, Y.H.; Sampath, H.; Carpenter, W.T.; Dugarrila, R.; Curran, J.; Blangero, J.; Hong, L.E.

2012-01-01

Introduction Elevated rate of aging-related biological and functional decline, termed accelerated aging, is reported in patients with schizophrenia (SCZ) and major depressive disorder (MDD). We used diffusion tensor imaging (DTI) derived fractional anisotropy (FA) as biomarkers of aging-related decline in white matter (WM) integrity to test the hypotheses of accelerated aging in SCZ and MDD. Methods The SCZ cohort was composed of 58/60 SCZ patients/controls (age=20–60years). MDD cohort was composed of 136/351 MDD patients/controls (age=20–79years). Main outcome measures were the diagnosis-by-age interaction on whole-brain-averaged WM FA values and FA values from twelve major WM tracts. Results Diagnosis-by-age interaction for the whole-brain average FA was significant for the SCZ (p=0.04) but not in MDD cohort (p=0.80). Diagnosis-by-age interaction was nominally significant (p<0.05) for five WM tracts for SCZ and for none of the tracts in the MDD cohort. Tract-specific heterochronicity of the onset of age-related decline in SCZ demonstrated strong negative correlations with the age-of- peak myelination and the rates of age-related decline obtained from normative sample (r=−0.61 and −0.80, p<0.05, respectively). No such trends existed for MDD cohort. Conclusion Cerebral WM showed accelerated aging in SCZ but not in MDD, suggesting some difference in the pathophysiology underlying their WM aging changes. Tract-specific heterochronicity of WM development modulated presentation of accelerated aging in SCZ: white matter tracts that matured later in life appeared more sensitive to the pathophysiology of SCZ and demonstrated more susceptibility to disorder-related accelerated decline in FA values with age. This trend was not observed in MDD cohort. PMID:23200529

Incidence of Fanconi anemia in children with congenital thumb anomalies referred for diepoxybutane testing.

PubMed

Webb, Michelle L; Rosen, Heather; Taghinia, Amir; McCarty, Erika R; Cerrato, Felecia; Upton, Joseph; Labow, Brian I

2011-06-01

Fanconi anemia (FA) is a rare genetic disorder of DNA repair that with near uniformity leads to bone marrow failure and resulting morbidity and mortality. Approximately 50% of FA patients are born with anomalies of the thumb or thumb and radius, and it has been recommended that all patients born with thumb anomalies undergo testing. However, the risk of FA in this population is unknown. We determined the incidence of FA in children with congenital thumb anomalies referred for FA testing and characterized those who tested positive. We queried our database for patients who presented with congenital thumb anomalies and who underwent diepoxybutane (DEB) testing for FA between 1999 and 2008 at Children's Hospital Boston and the Dana-Farber Cancer Institute. During this time period, 543 congenital thumb anomaly patients (235 with thumb hypoplasia) presented to our institution. A total of 81 patients with thumb abnormalities underwent DEB testing. Six patients (7% of those tested; 1% of the total; 3% of thumb hypoplasia patients) had a positive DEB test consistent with the diagnosis of FA; all had other non-upper-extremity anomalies associated with FA. Of 6 FA patients, 5 had bilateral involvement; all had some degree of thumb hypoplasia (3 also had radial dysplasia). Mean age at testing was 2.6 years (SD 4.3). Most of the patients tested had multiple physical anomalies (n = 66). The anomaly distribution was: thumb hypoplasia and radial dysplasia (n = 29), thumb hypoplasia (n = 26), radial polydactyly (n = 12), radial polydactyly and radial dysplasia (n = 1), and proximally placed thumb and radial dysplasia (n = 1). Twelve patients had other thumb anomalies. Although the incidence of FA in patients with thumb anomalies may be low, patients with thumb hypoplasia and other physical findings associated with FA, specifically café au lait spots and short stature, appear to have an increased risk of FA. Because hand surgeons see these patients early in life, they have the opportunity to refer these patients for FA testing to initiate early education, family genetic counseling, and treatment if warranted. Prognostic IV. Copyright © 2011 American Society for Surgery of the Hand. Published by Elsevier Inc. All rights reserved.

Quantitative analysis of diffusion tensor imaging (DTI) using statistical parametric mapping (SPM) for brain disorders

NASA Astrophysics Data System (ADS)

Lee, Jae-Seung; Im, In-Chul; Kang, Su-Man; Goo, Eun-Hoe; Kwak, Byung-Joon

2013-07-01

This study aimed to quantitatively analyze data from diffusion tensor imaging (DTI) using statistical parametric mapping (SPM) in patients with brain disorders and to assess its potential utility for analyzing brain function. DTI was obtained by performing 3.0-T magnetic resonance imaging for patients with Alzheimer's disease (AD) and vascular dementia (VD), and the data were analyzed using Matlab-based SPM software. The two-sample t-test was used for error analysis of the location of the activated pixels. We compared regions of white matter where the fractional anisotropy (FA) values were low and the apparent diffusion coefficients (ADCs) were increased. In the AD group, the FA values were low in the right superior temporal gyrus, right inferior temporal gyrus, right sub-lobar insula, and right occipital lingual gyrus whereas the ADCs were significantly increased in the right inferior frontal gyrus and right middle frontal gyrus. In the VD group, the FA values were low in the right superior temporal gyrus, right inferior temporal gyrus, right limbic cingulate gyrus, and right sub-lobar caudate tail whereas the ADCs were significantly increased in the left lateral globus pallidus and left medial globus pallidus. In conclusion by using DTI and SPM analysis, we were able to not only determine the structural state of the regions affected by brain disorders but also quantitatively analyze and assess brain function.

Prediction of fatty acid-binding residues on protein surfaces with three-dimensional probability distributions of interacting atoms.

PubMed

Mahalingam, Rajasekaran; Peng, Hung-Pin; Yang, An-Suei

2014-08-01

Protein-fatty acid interaction is vital for many cellular processes and understanding this interaction is important for functional annotation as well as drug discovery. In this work, we present a method for predicting the fatty acid (FA)-binding residues by using three-dimensional probability density distributions of interacting atoms of FAs on protein surfaces which are derived from the known protein-FA complex structures. A machine learning algorithm was established to learn the characteristic patterns of the probability density maps specific to the FA-binding sites. The predictor was trained with five-fold cross validation on a non-redundant training set and then evaluated with an independent test set as well as on holo-apo pair's dataset. The results showed good accuracy in predicting the FA-binding residues. Further, the predictor developed in this study is implemented as an online server which is freely accessible at the following website, http://ismblab.genomics.sinica.edu.tw/. Copyright © 2014 Elsevier B.V. All rights reserved.

White Matter Microstructure in Subjects with Attention-Deficit/Hyperactivity Disorder and Their Siblings

ERIC Educational Resources Information Center

Lawrence, Katherine E.; Levitt, Jennifer G.; Loo, Sandra K.; Ly, Ronald; Yee, Victor; O'Neill, Joseph; Alger, Jeffry; Narr, Katherine L.

2013-01-01

Objective: Previous voxel-based and regions-of-interest (ROI)-based diffusion tensor imaging (DTI) studies have found above-normal mean diffusivity (MD) and below-normal fractional anisotropy (FA) in subjects with attention-deficit/hyperactivity disorder (ADHD). However, findings remain mixed, and few studies have examined the contribution of ADHD…

Cloning and characterization of murine fanconi anemia group A gene: Fanca protein is expressed in lymphoid tissues, testis, and ovary.

PubMed

van de Vrugt, H J; Cheng, N C; de Vries, Y; Rooimans, M A; de Groot, J; Scheper, R J; Zhi, Y; Hoatlin, M E; Joenje, H; Arwert, F

2000-04-01

Fanconi anemia (FA) is an autosomal recessive disorder in humans characterized by bone marrow failure, cancer predisposition, and cellular hypersensitivity to cross-linking agents such as mitomycin C and diepoxybutane. FA genes display a caretaker function essential for maintenance of genomic integrity. We have cloned the murine homolog of FANCA, the gene mutated in the major FA complementation group (FA-A). The full-length mouse Fanca cDNA consists of 4503 bp and encodes a protein with a predicted molecular weight of 161 kDa. The deduced Fanca mouse protein shares 81% amino acid sequence similarity and 66% identity with the human protein. The nuclear localization signal and partial leucine zipper consensus motifs found in the human FANCA protein were also present in the murine homolog. In spite of the species difference, the murine Fanca cDNA was capable of correcting the cross-linker sensitive phenotype of human FA-A cells, suggesting functional conservation. Based on Northern as well as Western blots, Fanca was mainly expressed in lymphoid tissues, testis, and ovary. This expression pattern correlates with some of the clinical symptoms observed in FA patients. The availability of the murine Fanca cDNA now allows the gene to be studied in experimental mouse models.

Continuous in vivo infusion of interferon-gamma (IFN-γ) enhances engraftment of syngeneic wild-type cells in Fanca–/– and Fancg–/– mice

PubMed Central

Si, Yue; Ciccone, Samantha; Yang, Feng-Chun; Yuan, Jin; Zeng, Daisy; Chen, Shi; van de Vrugt, Henri J.; Critser, John; Arwert, Fre; Haneline, Laura S.; Clapp, D. Wade

2006-01-01

Fanconi anemia (FA) is a heterogeneous genetic disorder characterized by bone marrow (BM) failure and cancer susceptibility. Identification of the cDNAs of FA complementation types allows the potential of using gene transfer technology to introduce functional cDNAs as transgenes into autologous stem cells and provide a cure for the BM failure in FA patients. However, strategies to enhance the mobilization, transduction, and engraftment of exogenous stem cells are required to optimize efficacy prior to widespread clinical use. Hypersensitivity of Fancc–/– cells to interferon-gamma (IFN-γ), a nongenotoxic immune-regulatory cytokine, enhances engraftment of syngeneic wild-type (WT) cells in Fancc–/– mice. However, whether this phenotype is of broad relevance in other FA complementation groups is unresolved. Here we show that primitive and mature myeloid progenitors in Fanca–/– and Fancg–/– mice are hypersensitive to IFN-γ and that in vivo infusion of IFN-γ at clinically relevant concentrations was sufficient to allow consistent long-term engraftment of isogenic WT repopulating stem cells. Given that FANCA, FANCC, and FANCG complementation groups account for more than 90% of all FA patients, these data provide evidence that IFN-γ conditioning may be a useful nongenotoxic strategy for myelopreparation in FA patients. PMID:16946306

Continuous in vivo infusion of interferon-gamma (IFN-gamma) enhances engraftment of syngeneic wild-type cells in Fanca-/- and Fancg-/- mice.

PubMed

Si, Yue; Ciccone, Samantha; Yang, Feng-Chun; Yuan, Jin; Zeng, Daisy; Chen, Shi; van de Vrugt, Henri J; Critser, John; Arwert, Fre; Haneline, Laura S; Clapp, D Wade

2006-12-15

Fanconi anemia (FA) is a heterogeneous genetic disorder characterized by bone marrow (BM) failure and cancer susceptibility. Identification of the cDNAs of FA complementation types allows the potential of using gene transfer technology to introduce functional cDNAs as transgenes into autologous stem cells and provide a cure for the BM failure in FA patients. However, strategies to enhance the mobilization, transduction, and engraftment of exogenous stem cells are required to optimize efficacy prior to widespread clinical use. Hypersensitivity of Fancc-/- cells to interferon-gamma (IFN-gamma), a nongenotoxic immune-regulatory cytokine, enhances engraftment of syngeneic wild-type (WT) cells in Fancc-/- mice. However, whether this phenotype is of broad relevance in other FA complementation groups is unresolved. Here we show that primitive and mature myeloid progenitors in Fanca-/- and Fancg-/- mice are hypersensitive to IFN-gamma and that in vivo infusion of IFN-gamma at clinically relevant concentrations was sufficient to allow consistent long-term engraftment of isogenic WT repopulating stem cells. Given that FANCA, FANCC, and FANCG complementation groups account for more than 90% of all FA patients, these data provide evidence that IFN-gamma conditioning may be a useful nongenotoxic strategy for myelopreparation in FA patients.

Facile preparation of SERS and catalytically active Au nanostructures using furfuryl derivatives

NASA Astrophysics Data System (ADS)

Kim, Ki-Jung; Kim, Hyun-Chul; Park, Minsun; Huh, Seong

2017-08-01

Six different types of Au nanostructures with rough surfaces were readily prepared through the redox reactions between Au precursor, AuCl4-, and furfuryl derivatives without extra metal surface capping ligands, in deionized water at room temperature. Furfuryl alcohol (FA) or furfurylamine (FFA) was used as a sole reducing agent for the reduction of Au precursor. Both FA and FFA effectively polymerized during the redox reactions to form polyfuran polymers. These polymers are thought to act as surface capping ligands during the formation of Au nanostructures. Experiments were conducted with three different concentrations of each furfuryl derivative. Interestingly, Au particles prepared from the reaction with varying concentration of FA or FFA showed large differences in size, and revealed that the higher the ratios of [FA]/[AuCl4-] or [FFA]/[AuCl4-], the smaller the size of Au particles. The size of Au particles was in the range of 1 μm to under 30 nm. Among these samples, two nanostructured Au particles, AuFA-4 and AuFFA-1, deposited on a Si wafer by a simple drop-casting method, were revealed as highly active surface-enhanced Raman scattering (SERS) substrates for the detection of methylene blue (MB) and crystal violet (CV). High SERS enhancement factors (EFs) of 106 ∼ 108 for MB and CV were observed. Small size Au nanoparticles (AuFFA-2 and AuFFA-4) were also found to be very active for the catalytic hydrogenation of 4-nitrophenol to 4-aminophenol in the presence of NaBH4 at room temperature. AuFFA-2 could be recycled eight times, without losing its activity.

White-matter connectivity and methylphenidate-induced changes in attentional performance according to α2A-adrenergic receptor gene polymorphisms in Korean children with attention-deficit hyperactivity disorder.

PubMed

Park, Subin; Hong, Soon-Beom; Kim, Jae-Won; Yang, Young-Hui; Park, Min-Hyeon; Kim, Boong-Nyun; Shin, Min-Sup; Yoo, Hee-Jeong; Cho, Soo-Churl

2013-01-01

The authors examined the association between the MspI C/G and DraI C/T genotypes of the α2A-adrenergic receptor gene and white-matter connectivity and attentional performance before and after medication in 53 children with attention-deficit hyperactivity disorder. Subjects who carried the T allele at the DraI polymorphism showed fewer changes in the mean commission error scores after 8 weeks of medication and decreased fractional anisotropy (FA) values in the right middle frontal cortex than subjects without the T allele. Subjects with the C allele at the MspI polymorphism showed decreased FA values in the right postcentral gyrus than subjects without.

Otologic manifestations of Fanconi anemia and other inherited bone marrow failure syndromes.

PubMed

Kalejaiye, Adedoyin; Giri, Neelam; Brewer, Carmen C; Zalewski, Christopher K; King, Kelly A; Adams, Charleen D; Rosenberg, Philip S; Kim, H Jeffrey; Alter, Blanche P

2016-12-01

The inherited bone marrow failure syndromes (IBMFSs) are diverse disorders with syndrome-specific features; their otologic and audiologic manifestations have not been well described. Our objective was to characterize these in patients with Fanconi anemia (FA), dyskeratosis congenita (DC), Diamond-Blackfan anemia (DBA), and Shwachman-Diamond syndrome (SDS), and to determine the association between physical findings and hearing loss. Patients with an IBMFS underwent comprehensive clinical and laboratory evaluations and testing for syndrome-specific gene mutations. Hearing loss was measured by pure tone audiometry and otologic abnormalities by otomicroscopy. Patients included 33 with FA, 37 with DC, 32 with DBA, and nine with SDS. Hearing loss was most frequent in patients with FA (45%) and DBA (14%). The most common type of hearing loss in FA was conductive (65%). Absent or hypoplastic radius, noted in 21% of the patients with FA, was associated with hearing loss in all cases. Otomicroscopy was abnormal in 66% of patients with FA. Characteristic ear abnormalities included small tympanic membrane (66%), malformed malleus (57%), aberrant tympanic bony island (48%), narrow external auditory canal (EAC) (32%), and abnormal course of chorda tympani (34%). Ear malformations were almost always associated with hearing loss. Hearing loss was rare in patients with DC and SDS. FA is the major IBMFS with associated hearing loss, which is most commonly conductive. Radial hypoplasia or aplasia and characteristic congenital ear malformations are associated with hearing loss in patients with FA. Recognition of these syndrome-specific abnormalities should lead to earlier management of hearing loss. © 2016 Wiley Periodicals, Inc.

Molecular and genealogical evidence for a founder effect in Fanconi anemia families of the Afrikaner population of South Africa.

PubMed

Tipping, A J; Pearson, T; Morgan, N V; Gibson, R A; Kuyt, L P; Havenga, C; Gluckman, E; Joenje, H; de Ravel, T; Jansen, S; Mathew, C G

2001-05-08

Fanconi anemia (FA) is a rare, genetically heterogeneous autosomal recessive disorder associated with progressive aplastic anemia, congenital abnormalities, and cancer. FA has a very high incidence in the Afrikaner population of South Africa, possibly due to a founder effect. Previously we observed allelic association between polymorphic markers flanking the FA group A gene (FANCA) and disease chromosomes in Afrikaners. We genotyped 26 FA families with microsatellite and single nucleotide polymorphic markers and detected five FANCA haplotypes. Mutation scanning of the FANCA gene revealed association of these haplotypes with four different mutations. The most common was an intragenic deletion of exons 12-31, accounting for 60% of FA chromosomes in 46 unrelated Afrikaner FA patients, while two other mutations accounted for an additional 20%. Screening for these mutations in the European populations ancestral to the Afrikaners detected one patient from the Western Ruhr region of Germany who was heterozygous for the major deletion. The mutation was associated with the same unique FANCA haplotype as in Afrikaner patients. Genealogical investigation of 12 Afrikaner families with FA revealed that all were descended from a French Huguenot couple who arrived at the Cape on June 5, 1688, whereas mutation analysis showed that the carriers of the major mutation were descendants of this same couple. The molecular and genealogical evidence is consistent with transmission of the major mutation to Western Germany and the Cape near the end of the 17th century, confirming the existence of a founder effect for FA in South Africa.

Molecular and genealogical evidence for a founder effect in Fanconi anemia families of the Afrikaner population of South Africa

PubMed Central

Tipping, A. J.; Pearson, T.; Morgan, N. V.; Gibson, R. A.; Kuyt, L. P.; Havenga, C.; Gluckman, E.; Joenje, H.; de Ravel, T.; Jansen, S.; Mathew, C. G.

2001-01-01

Fanconi anemia (FA) is a rare, genetically heterogeneous autosomal recessive disorder associated with progressive aplastic anemia, congenital abnormalities, and cancer. FA has a very high incidence in the Afrikaner population of South Africa, possibly due to a founder effect. Previously we observed allelic association between polymorphic markers flanking the FA group A gene (FANCA) and disease chromosomes in Afrikaners. We genotyped 26 FA families with microsatellite and single nucleotide polymorphic markers and detected five FANCA haplotypes. Mutation scanning of the FANCA gene revealed association of these haplotypes with four different mutations. The most common was an intragenic deletion of exons 12–31, accounting for 60% of FA chromosomes in 46 unrelated Afrikaner FA patients, while two other mutations accounted for an additional 20%. Screening for these mutations in the European populations ancestral to the Afrikaners detected one patient from the Western Ruhr region of Germany who was heterozygous for the major deletion. The mutation was associated with the same unique FANCA haplotype as in Afrikaner patients. Genealogical investigation of 12 Afrikaner families with FA revealed that all were descended from a French Huguenot couple who arrived at the Cape on June 5, 1688, whereas mutation analysis showed that the carriers of the major mutation were descendants of this same couple. The molecular and genealogical evidence is consistent with transmission of the major mutation to Western Germany and the Cape near the end of the 17th century, confirming the existence of a founder effect for FA in South Africa. PMID:11344308

MRI-visual order-disorder micellar nanostructures for smart cancer theranostics.

PubMed

Patra, Hirak K; Ul Khaliq, Nisar; Romu, Thobias; Wiechec, Emilia; Borga, Magnus; Turner, Anthony P F; Tiwari, Ashutosh

2014-04-01

The development of MRI-visual order-disorder structures for cancer nanomedicine explores a pH-triggered mechanism for theragnosis of tumor hallmark functions. Superparamagnetic iron oxide nanoparticles (SPIONs) stabilized with amphiphilic poly(styrene)-b-poly(acrylic acid)-doxorubicin with folic acid (FA) surfacing are employed as a multi-functional approach to specifically target, diagnose, and deliver drugs via a single nanoscopic platform for cancer therapy. The functional aspects of the micellar nanocomposite is investigated in vitro using human breast SkBr3 and colon cancer HCT116 cell lines for the delivery, release, localization, and anticancer activity of the drug. For the first time, concentration-dependent T2 -weighted MRI contrast for a monolayer of clustered cancer cells is shown. The pH tunable order-disorder transition of the core-shell structure induces the relative changes in MRI contrast. The outcomes elucidate the potential of this material for smart cancer theranostics by delivering non-invasive real-time diagnosis, targeted therapy, and monitoring the course and response of the action before, during, and after the treatment regimen. © 2013 WILEY-VCH Verlag GmbH & Co. KGaA, Weinheim.

Process optimization for the preparation of oligomycin-loaded folate-conjugated chitosan nanoparticles as a tumor-targeted drug delivery system using a two-level factorial design method.

PubMed

Zu, Yuangang; Zhao, Qi; Zhao, Xiuhua; Zu, Shuchong; Meng, Li

2011-01-01

Oligomycin-A (Oli-A), an anticancer drug, was loaded to the folate (FA)-conjugated chitosan as a tumor-targeted drug delivery system for the purpose of overcoming the nonspecific targeting characteristics and the hydrophobicity of the compound. The two-level factorial design (2-LFD) was applied to modeling the preparation process, which was composed of five independent variables, namely FA-conjugated chitosan (FA-CS) concentration, Oli-A concentration, sodium tripolyphosphate (TPP) concentration, the mass ratio of FA-CS to TPP, and crosslinking time. The mean particle size (MPS) and the drug loading rate (DLR) of the resulting Oli-loaded FA-CS nanoparticles (FA-Oli-CSNPs) were used as response variables. The interactive effects of the five independent variables on the response variables were studied. The characteristics of the nanoparticles, such as amount of FA conjugation, drug entrapment rate (DER), DLR, surface morphology, and release kinetics properties in vitro were investigated. The FA-Oli-CSNPs with MPS of 182.6 nm, DER of 17.3%, DLR of 58.5%, and zeta potential (ZP) of 24.6 mV were obtained under optimum conditions. The amount of FA conjugation was 45.9 mg/g chitosan. The FA-Oli-CSNPs showed sustained-release characteristics for 576 hours in vitro. The results indicated that FA-Oli-CSNPs obtained as a targeted drug delivery system could be effective in the therapy of leukemia in the future.

Leaching Behavior of Selected Trace and Toxic Metals in Coal Fly Ash Samples Collected from Two Thermal Power Plants, India.

PubMed

Sandeep, P; Sahu, S K; Kothai, P; Pandit, G G

2016-09-01

Studies on leaching behavior of metals associated with coal fly ash (FA) are of great concern because of possible contamination of the aquatic environment. In the present study, leaching behavior of metals (As, Se, Cr, Pb, V, Zn, etc.) in two different FA samples (FA1 and FA2) was investigated at various pH (2-12), temperatures of leachate solution and using TCLP. At pH 2, the highest leaching was observed for Fe (21.6 and 32.8 µg/g), whereas at pH 12, Arsenic was found to have the highest leaching (1.5 and 2.4 µg/g) in FA1 and FA2. Leachate solution temperature showed a positive effect on the metal's leachability. In TCLP, most of the metal's leachability was observed to be higher than that of batch leaching tests. The present study suggests that, leaching of As and Se from FA samples can moderately affect ground/surface water quality at the study locations.

Substrate-Triggered Exosite Binding: Synergistic Dendrimer/Folic Acid Action for Achieving Specific, Tight-Binding to Folate Binding Protein.

PubMed

Chen, Junjie; van Dongen, Mallory A; Merzel, Rachel L; Dougherty, Casey A; Orr, Bradford G; Kanduluru, Ananda Kumar; Low, Philip S; Marsh, E Neil G; Banaszak Holl, Mark M

2016-03-14

Polymer-ligand conjugates are designed to bind proteins for applications as drugs, imaging agents, and transport scaffolds. In this work, we demonstrate a folic acid (FA)-triggered exosite binding of a generation five poly(amidoamine) (G5 PAMAM) dendrimer scaffold to bovine folate binding protein (bFBP). The protein exosite is a secondary binding site on the protein surface, separate from the FA binding pocket, to which the dendrimer binds. Exosite binding is required to achieve the greatly enhanced binding constants and protein structural change observed in this study. The G5Ac-COG-FA1.0 conjugate bound tightly to bFBP, was not displaced by a 28-fold excess of FA, and quenched roughly 80% of the initial fluorescence. Two-step binding kinetics were measured using the intrinsic fluorescence of the FBP tryptophan residues to give a KD in the low nanomolar range for formation of the initial G5Ac-COG-FA1.0/FBP* complex, and a slow conversion to the tight complex formed between the dendrimer and the FBP exosite. The extent of quenching was sensitive to the choice of FA-dendrimer linker chemistry. Direct amide conjugation of FA to G5-PAMAM resulted in roughly 50% fluorescence quenching of the FBP. The G5Ac-COG-FA, which has a longer linker containing a 1,2,3-triazole ring, exhibited an ∼80% fluorescence quenching. The binding of the G5Ac-COG-FA1.0 conjugate was compared to poly(ethylene glycol) (PEG) conjugates of FA (PEGn-FA). PEG2k-FA had a binding strength similar to that of FA, whereas other PEG conjugates with higher molecular weight showed weaker binding. However, no PEG conjugates gave an increased degree of total fluorescence quenching.

The Fanconi anemia pathway limits the severity of mutagenesis.

PubMed

Hinz, John M; Nham, Peter B; Salazar, Edmund P; Thompson, Larry H

2006-08-13

Fanconi anemia (FA) is a developmental and cancer predisposition disorder in which key, yet unknown, physiological events promoting chromosome stability are compromised. FA cells exhibit excess metaphase chromatid breaks and are universally hypersensitive to DNA interstrand crosslinking agents. Published mutagenesis data from single-gene mutation assays show both increased and decreased mutation frequencies in FA cells. In this review we discuss the data from the literature and from our isogenic fancg knockout hamster CHO cells, and interpret these data within the framework of a molecular model that accommodates these seemingly divergent observations. In FA cells, reduced rates of recovery of viable X-linked hypoxanthine phosphoribosyltransferase (hprt) mutants are characteristically observed for diverse mutagenic agents, but also in untreated cultures, indicating the relevance of the FA pathway for processing assorted DNA lesions. We ascribe these reductions to: (1) impaired mutagenic translesion synthesis within hprt during DNA replication and (2) lethality of mutant cells following replication fork breakage on the X chromosome, caused by unrepaired double-strand breaks or large deletions/translocations encompassing essential genes flanking hprt. These findings, along with studies showing increased spontaneous mutability of FA cells at two autosomal loci, support a model in which FA proteins promote both translesion synthesis at replication-blocking lesions and repair of broken replication forks by homologous recombination and DNA end joining. The essence of this model is that the FANC protein pathway serves to restrict the severity of mutational outcome by favoring base substitutions and small deletions over larger deletions and chromosomal rearrangements.

White matter connectivity and Internet gaming disorder

PubMed Central

Jeong, Bum Seok; Han, Doug Hyun; Kim, Sun Mi; Lee, Sang Won; Renshaw, Perry F.

2017-01-01

Internet use and on-line game play stimulate corticostriatal-limbic circuitry in both healthy subjects and subjects with Internet gaming disorder (IGD). We hypothesized that increased fractional anisotropy (FA) with decreased radial diffusivity (RD) would be observed in IGD subjects, compared with healthy control subjects, and that these white matter indices would be associated with clinical variables including duration of illness and executive function. We screened 181 male patients in order to recruit a large number (n = 58) of IGD subjects without psychiatric co-morbidity as well as 26 male healthy comparison subjects. Multiple diffusion-weighted images were acquired using a 3.0 Tesla magnetic resonance imaging scanner. Tract-based spatial statistics was applied to compare group differences in diffusion tensor imaging (DTI) metrics between IGD and healthy comparison subjects. IGD subjects had increased FA values within forceps minor, right anterior thalamic radiation, right corticospinal tract, right inferior longitudinal fasciculus, right cingulum to hippocampus and right inferior fronto-occipital fasciculus (IFOF) as well as parallel decreases in RD value within forceps minor, right anterior thalamic radiation and IFOF relative to healthy control subjects. In addition, the duration of illness in IGD subjects was positively correlated with the FA values (integrity of white matter fibers) and negatively correlated with RD scores (diffusivity of axonal density) of whole brain white matter. In IGD subjects without psychiatric co-morbidity, our DTI results suggest that increased myelination (increased FA and decreased RD values) in right-sided frontal fiber tracts may be the result of extended game play. PMID:25899390

Microstructure abnormalities in adolescents with internet addiction disorder.

PubMed

Yuan, Kai; Qin, Wei; Wang, Guihong; Zeng, Fang; Zhao, Liyan; Yang, Xuejuan; Liu, Peng; Liu, Jixin; Sun, Jinbo; von Deneen, Karen M; Gong, Qiyong; Liu, Yijun; Tian, Jie

2011-01-01

Recent studies suggest that internet addiction disorder (IAD) is associated with structural abnormalities in brain gray matter. However, few studies have investigated the effects of internet addiction on the microstructural integrity of major neuronal fiber pathways, and almost no studies have assessed the microstructural changes with the duration of internet addiction. We investigated the morphology of the brain in adolescents with IAD (N = 18) using an optimized voxel-based morphometry (VBM) technique, and studied the white matter fractional anisotropy (FA) changes using the diffusion tensor imaging (DTI) method, linking these brain structural measures to the duration of IAD. We provided evidences demonstrating the multiple structural changes of the brain in IAD subjects. VBM results indicated the decreased gray matter volume in the bilateral dorsolateral prefrontal cortex (DLPFC), the supplementary motor area (SMA), the orbitofrontal cortex (OFC), the cerebellum and the left rostral ACC (rACC). DTI analysis revealed the enhanced FA value of the left posterior limb of the internal capsule (PLIC) and reduced FA value in the white matter within the right parahippocampal gyrus (PHG). Gray matter volumes of the DLPFC, rACC, SMA, and white matter FA changes of the PLIC were significantly correlated with the duration of internet addiction in the adolescents with IAD. Our results suggested that long-term internet addiction would result in brain structural alterations, which probably contributed to chronic dysfunction in subjects with IAD. The current study may shed further light on the potential brain effects of IAD.

Multimodal voxel-based meta-analysis of white matter abnormalities in obsessive-compulsive disorder.

PubMed

Radua, Joaquim; Grau, Mar; van den Heuvel, Odile A; Thiebaut de Schotten, Michel; Stein, Dan J; Canales-Rodríguez, Erick J; Catani, Marco; Mataix-Cols, David

2014-06-01

White matter (WM) abnormalities have long been suspected in obsessive-compulsive disorder (OCD) but the available evidence has been inconsistent. We conducted the first multimodal meta-analysis of WM volume (WMV) and fractional anisotropy (FA) studies in OCD. All voxel-wise studies comparing WMV or FA between patients with OCD and healthy controls in the PubMed, ScienceDirect, Google Scholar, Web of Knowledge and Scopus databases were retrieved. Manual searches were also conducted and authors were contacted soliciting additional data. Thirty-four data sets were identified, of which 22 met inclusion criteria (five of them unpublished; comprising 537 adult and pediatric patients with OCD and 575 matched healthy controls). Whenever possible, raw statistical parametric maps were also obtained from the authors. Peak and raw WMV and FA data were combined using novel multimodal meta-analytic methods implemented in effect-size signed differential mapping. Patients with OCD showed widespread WM abnormalities, but findings were particularly robust in the anterior midline tracts (crossing between anterior parts of cingulum bundle and body of corpus callosum), which showed both increased WMV and decreased FA, possibly suggesting an increase of fiber crossing in these regions. This finding was also observed when the analysis was limited to adult participants, and especially pronounced in samples with a higher proportion of medicated patients. Therefore, patients with OCD may have widespread WM abnormalities, particularly evident in anterior midline tracts, although these changes might be, at least in part, attributable to the effects of therapeutic drugs.

Oral cancer in Fanconi anemia: Review of 121 cases.

PubMed

Furquim, Camila Pinheiro; Pivovar, Allana; Amenábar, José Miguel; Bonfim, Carmem; Torres-Pereira, Cassius Carvalho

2018-05-01

Fanconi anemia (FA) is a rare autosomal recessive genetic disorder characterized by aplastic anemia, progressive pancytopenia, congenital anomalies, and increased risk of cancer development. After hematopoietic stem cell transplant (HSCT), patients have an estimated 500-fold increase in the risk of developing head and neck cancer compared to a non-affected, and the oral cavity is affected in one-third of cases. Thus, this study aimed to better understand the natural history of oral cavity cancer in patients affected by FA. After conducting a keyword search on MEDLINE, we found 121 cases of oral cavity cancer in patients who had been affected by FA. In conclusion, HSCT may increase the risks of oral cancer development, especially after 5 years after the transplant. In the normal population, the tongue is the most affected area. FA patients should be informed of the risks of oral malignant transformation and encouraged to be undergo medical surveillance. Copyright © 2018 Elsevier B.V. All rights reserved.

Intrinsic disruption of white matter microarchitecture in first-episode, drug-naive major depressive disorder: A voxel-based meta-analysis of diffusion tensor imaging.

PubMed

Chen, Guangxiang; Guo, Yi; Zhu, Hongyan; Kuang, Weihong; Bi, Feng; Ai, Hua; Gu, Zhongwei; Huang, Xiaoqi; Lui, Su; Gong, Qiyong

2017-06-02

Previous studies have demonstrated the influences of episodes and antidepressant drugs on white matter (WM) in patients with major depressive disorder (MDD). However, most diffusion tensor imaging (DTI) studies included highly heterogeneous individuals with different numbers of depressive episodes or medication status. To exclude the confounding effects of multiple episodes or medication, we conducted a quantitative voxel-based meta-analysis of fractional anisotropy (FA) in patients with first-episode, drug-naive MDD to identify the intrinsic WM alterations involved in the pathogenesis of MDD. The pooled meta-analysis revealed significant FA reductions in the body of the corpus callosum (CC), bilateral anterior limb of the internal capsule (ALIC), right inferior temporal gyrus (ITG) and right superior frontal gyrus (SFG) in MDD patients relative to healthy controls. Meta-regression analyses revealed that FA reduction in the right ALIC and right SFG was negatively correlated with symptom severity and duration of depression, respectively. Our findings provide robust evidence that the WM impairments in the interhemispheric connections and frontal-subcortical neuronal circuits may play an important role in MDD pathogenesis. Copyright © 2017. Published by Elsevier Inc.

A systematic review and meta-analysis of tract-based spatial statistics studies regarding attention-deficit/hyperactivity disorder.

PubMed

Chen, Lizhou; Hu, Xinyu; Ouyang, Luo; He, Ning; Liao, Yi; Liu, Qi; Zhou, Ming; Wu, Min; Huang, Xiaoqi; Gong, Qiyong

2016-09-01

Diffusion tensor imaging (DTI) studies that use tract-based spatial statistics (TBSS) have demonstrated the microstructural abnormalities of white matter (WM) in patients with attention-deficit/hyperactivity disorder (ADHD); however, robust conclusions have not yet been drawn. The present study integrated the findings of previous TBSS studies to determine the most consistent WM alterations in ADHD via a narrative review and meta-analysis. The literature search was conducted through October 2015 to identify TBSS studies that compared fractional anisotropy (FA) between ADHD patients and healthy controls. FA reductions were identified in the splenium of the corpus callosum (CC) that extended to the right cingulum, right sagittal stratum, and left tapetum. The first two clusters retained significance in the sensitivity analysis and in all subgroup analyses. The FA reduction in the CC splenium was negatively associated with the mean age of the ADHD group. We hypothesize that, in addition to the fronto-striatal-cerebellar circuit, the disturbed WM matter tracts that integrate the bilateral hemispheres and posterior-brain circuitries play a crucial role in the pathophysiology of ADHD. Copyright © 2016 Elsevier Ltd. All rights reserved.

Structural insights into the functions of the FANCM-FAAP24 complex in DNA repair

PubMed Central

Yang, Hui; Zhang, Tianlong; Tao, Ye; Wang, Fang; Tong, Liang; Ding, Jianping

2013-01-01

Fanconi anemia (FA) is a genetically heterogeneous disorder associated with deficiencies in the FA complementation group network. FA complementation group M (FANCM) and FA-associated protein 24 kDa (FAAP24) form a stable complex to anchor the FA core complex to chromatin in repairing DNA interstrand crosslinks. Here, we report the first crystal structure of the C-terminal segment of FANCM in complex with FAAP24. The C-terminal segment of FANCM and FAAP24 both consist of a nuclease domain at the N-terminus and a tandem helix-hairpin-helix (HhH)2 domain at the C-terminus. The FANCM-FAAP24 complex exhibits a similar architecture as that of ApXPF. However, the variations of several key residues and the electrostatic property at the active-site region render a catalytically inactive nuclease domain of FANCM, accounting for the lack of nuclease activity. We also show that the first HhH motif of FAAP24 is a potential binding site for DNA, which plays a critical role in targeting FANCM-FAAP24 to chromatin. These results reveal the mechanistic insights into the functions of FANCM-FAAP24 in DNA repair. PMID:24003026

Hematopoietic cell transplantation in Fanconi anemia: current evidence, challenges and recommendations.

PubMed

Ebens, Christen L; MacMillan, Margaret L; Wagner, John E

2017-01-01

Hematopoietic cell transplantation for Fanconi Anemia (FA) has improved dramatically over the past 40 years. With an enhanced understanding of the intrinsic DNA-repair defect and pathophysiology of hematopoietic failure and leukemogenesis, sequential changes to conditioning and graft engineering have significantly improved the expectation of survival after allogeneic hematopoietic cell transplantation (alloHCT) with incidence of graft failure decreased from 35% to <10% and acute graft-versus-host disease (GVHD) from >40% to <10%. Today, five-year overall survival exceeds 90% in younger FA patients with bone marrow failure but remains about 50% in those with hematologic malignancy. Areas covered: We review the evolution of alloHCT contributing to decreased rates of transplant related complications; highlight current challenges including poorer outcomes in cases of clonal hematologic disorders, alloHCT impact on endocrine function and intrinsic FA risk of epithelial malignancies; and describe investigational therapies for prevention and treatment of the hematologic manifestations of FA. Expert commentary: Current methods allow for excellent survival following alloHCT for FA associated BMF irrespective of donor hematopoietic cell source. Alternative curative approaches, such as gene therapy, are being explored to eliminate the risks of GVHD and minimize therapy-related adverse effects.

Evolutionary aspects of diet: the omega-6/omega-3 ratio and the brain.

PubMed

Simopoulos, Artemis P

2011-10-01

Several sources of information suggest that human beings evolved on a diet that had a ratio of omega-6 to omega-3 fatty acids (FA) of about 1/1; whereas today, Western diets have a ratio of 10/1 to 20-25/1, indicating that Western diets are deficient in omega-3 FA compared with the diet on which humans evolved and their genetic patterns were established. Omega-6 and omega-3 FA are not interconvertible in the human body and are important components of practically all cell membranes. Studies with nonhuman primates and human newborns indicate that docosahexaenoic acid (DHA) is essential for the normal functional development of the brain and retina, particularly in premature infants. DHA accounts for 40% of the membrane phospholipid FA in the brain. Both eicosapentaenoic acid (EPA) and DHA have an effect on membrane receptor function and even neurotransmitter generation and metabolism. There is growing evidence that EPA and DHA could play a role in hostility and violence in addition to the beneficial effects in substance abuse disorders and alcoholism. The balance of omega-6 and omega-3 FA is important for homeostasis and normal development throughout the life cycle.

Update of the human and mouse Fanconi anemia genes.

PubMed

Dong, Hongbin; Nebert, Daniel W; Bruford, Elspeth A; Thompson, David C; Joenje, Hans; Vasiliou, Vasilis

2015-11-24

Fanconi anemia (FA) is a recessively inherited disease manifesting developmental abnormalities, bone marrow failure, and increased risk of malignancies. Whereas FA has been studied for nearly 90 years, only in the last 20 years have increasing numbers of genes been implicated in the pathogenesis associated with this genetic disease. To date, 19 genes have been identified that encode Fanconi anemia complementation group proteins, all of which are named or aliased, using the root symbol "FANC." Fanconi anemia subtype (FANC) proteins function in a common DNA repair pathway called "the FA pathway," which is essential for maintaining genomic integrity. The various FANC mutant proteins contribute to distinct steps associated with FA pathogenesis. Herein, we provide a review update of the 19 human FANC and their mouse orthologs, an evolutionary perspective on the FANC genes, and the functional significance of the FA DNA repair pathway in association with clinical disorders. This is an example of a set of genes--known to exist in vertebrates, invertebrates, plants, and yeast--that are grouped together on the basis of shared biochemical and physiological functions, rather than evolutionary phylogeny, and have been named on this basis by the HUGO Gene Nomenclature Committee (HGNC).

Mycoplasma salivarium as a Dominant Coloniser of Fanconi Anaemia Associated Oral Carcinoma

PubMed Central

Henrich, Birgit; Rumming, Madis; Sczyrba, Alexander; Velleuer, Eunike; Dietrich, Ralf; Gerlach, Wolfgang; Gombert, Michael; Rahn, Sebastian; Stoye, Jens; Borkhardt, Arndt; Fischer, Ute

2014-01-01

Mycoplasma salivarium belongs to the class of the smallest self-replicating Tenericutes and is predominantly found in the oral cavity of humans. In general it is considered as a non-pathogenic commensal. However, some reports point to an association with human diseases. M. salivarium was found e.g. as causative agent of a submasseteric abscess, in necrotic dental pulp, in brain abscess and clogged biliary stent. Here we describe the detection of M. salivarium on the surface of a squamous cell carcinoma of the tongue of a patient with Fanconi anaemia (FA). FA is an inherited bone marrow failure syndrome based on defective DNA-repair that increases the risk of carcinomas especially oral squamous cell carcinoma. Employing high coverage, massive parallel Roche/454-next-generation-sequencing of 16S rRNA gene amplicons we analysed the oral microbiome of this FA patient in comparison to that of an FA patient with a benign leukoplakia and five healthy individuals. The microbiota of the FA patient with leukoplakia correlated well with that of the healthy controls. A dominance of Streptococcus, Veillonella and Neisseria species was typically observed. In contrast, the microbiome of the cancer bearing FA patient was dominated by Pseudomonas aeruginosa at the healthy sites, which changed to a predominance of 98% M. salivarium on the tumour surface. Quantification of the mycoplasma load in five healthy, two tumour- and two leukoplakia-FA patients by TaqMan-PCR confirmed the prevalence of M. salivarium at the tumour sites. These new findings suggest that this mycoplasma species with its reduced coding capacity found ideal breeding grounds at the tumour sites. Interestingly, the oral cavity of all FA patients and especially samples at the tumour sites were in addition positive for Candida albicans. It remains to be elucidated in further studies whether M. salivarium can be used as a predictive biomarker for tumour development in these patients. PMID:24642836

Facies transition and depositional architecture of the Late Eocene tide-dominated delta in northern coast of Birket Qarun, Fayum, Egypt

NASA Astrophysics Data System (ADS)

Abdel-Fattah, Zaki A.

2016-07-01

Late Eocene successions in the Fayum Depression display notable facies transition from open-marine to brackish-marine realms. Stratigraphic and sedimentologic characteristics of the depositional facies are integrated with ichnological data for the recognition of four facies associations (FA1 to FA4). The transition from open-marine sandstones (FA1) to the brackish-marine deposits (FA2) heralds a transgressive - regressive dislocation. The shallowing- and coarsening-upward progradation from the basal prodelta mudstone-dominated facies (FA2a) to deltafront heterolithics (FA2b) and sandstone facies (FA2c) are overlain by finning-upward delta plain deposits which are expressed by the delta plain mudstone (FA2d) and erosive-based distributary channel fills (FA4). Prodelta/deltfront deposits of FA2 are arranged in thinning- and coarsening-upward parasequences which are stacked in a shallowing-upward progressive cycle. Shallow-marine fossiliferous sandstones (FA3) mark the basal part of each parasequence. Stratigraphic and depositional architectures reflect a tide-dominated delta rather than an estuarine and incised valley (IV) model. This can be evinced by the progressive facies architecture, absence of basal regional incision or a subaerial unconformity and the stratigraphic position above a maximum flooding surface (MFS), in addition to the presence of multiple tidally-influenced distributary channels. Stratigraphic and depositional characteristics of the suggested model resemble those of modern tide-dominated deltaic systems. Accordingly, this model contributes to our understanding of the depositional models for analogous brackish-marine environments, particularly tide-dominated deltas in the rock record.

Attentional Profiles and White Matter Correlates in Attention-Deficit/Hyperactivity Disorder Predominantly Inattentive Type

PubMed Central

Rossi, Adriana Suzart Ungaretti; de Moura, Luciana Monteiro; de Mello, Claudia Berlim; de Souza, Altay Alves Lino; Muszkat, Mauro; Bueno, Orlando Francisco Amodeo

2015-01-01

Attention-deficit/hyperactivity disorder (ADHD) is a widely studied neurodevelopmental disorder. It is a highly heterogeneous condition, encompassing different types of expression. The predominantly inattentive type is the most prevalent and the most stable over the lifetime, yet it is the least-studied presentation. To increase understanding of its cognitive profile, 29 children with attention-deficit/hyperactivity disorder of predominantly inattentive type (ADHD-I) and 29 matched controls, aged 7–15 years, had their attentional abilities assessed through the Conners’ continuous performance test. Diffusion tensor imaging data were collected for all of the participants using a 3.0-T MRI system. Fractional anisotropy (FA) values were obtained for 20 fiber tracts, and brain-behavior correlations were calculated for 42 of the children. The ADHD-I children differed significantly from the typically developing (TD) children with respect to attentional measures, such as the ability to maintain response-time consistency throughout the task (Hit RT SE and Variability), vigilance (Hit RT ISI and Hit RT ISI SE), processing speed (Hit RT), selective attention (Omissions), sustained attention (Hit RT Block Change), error profile (Response Style), and inhibitory control (Perseverations). Evidence of significant differences between the ADHD-I and the TD participants was not found with respect to the mean FA values in the fiber tracts analyzed. Moderate and strong correlations between performance on the attention indicators and the tract-average FA values were found for the ADHD-I group. Our results contribute to a better characterization of the attentional profile of ADHD-I individuals and suggest that in children and adolescents with ADHD-I, attentional performance is mainly associated with the white matter structure of the long associative fibers that connect anterior–posterior brain areas. PMID:26441684

Attentional Profiles and White Matter Correlates in Attention-Deficit/Hyperactivity Disorder Predominantly Inattentive Type.

PubMed

Rossi, Adriana Suzart Ungaretti; de Moura, Luciana Monteiro; de Mello, Claudia Berlim; de Souza, Altay Alves Lino; Muszkat, Mauro; Bueno, Orlando Francisco Amodeo

2015-01-01

Attention-deficit/hyperactivity disorder (ADHD) is a widely studied neurodevelopmental disorder. It is a highly heterogeneous condition, encompassing different types of expression. The predominantly inattentive type is the most prevalent and the most stable over the lifetime, yet it is the least-studied presentation. To increase understanding of its cognitive profile, 29 children with attention-deficit/hyperactivity disorder of predominantly inattentive type (ADHD-I) and 29 matched controls, aged 7-15 years, had their attentional abilities assessed through the Conners' continuous performance test. Diffusion tensor imaging data were collected for all of the participants using a 3.0-T MRI system. Fractional anisotropy (FA) values were obtained for 20 fiber tracts, and brain-behavior correlations were calculated for 42 of the children. The ADHD-I children differed significantly from the typically developing (TD) children with respect to attentional measures, such as the ability to maintain response-time consistency throughout the task (Hit RT SE and Variability), vigilance (Hit RT ISI and Hit RT ISI SE), processing speed (Hit RT), selective attention (Omissions), sustained attention (Hit RT Block Change), error profile (Response Style), and inhibitory control (Perseverations). Evidence of significant differences between the ADHD-I and the TD participants was not found with respect to the mean FA values in the fiber tracts analyzed. Moderate and strong correlations between performance on the attention indicators and the tract-average FA values were found for the ADHD-I group. Our results contribute to a better characterization of the attentional profile of ADHD-I individuals and suggest that in children and adolescents with ADHD-I, attentional performance is mainly associated with the white matter structure of the long associative fibers that connect anterior-posterior brain areas.

White matter tract integrity is associated with antidepressant response to lurasidone in bipolar depression.

PubMed

Lan, Martin J; Rubin-Falcone, Harry; Motiwala, Fatima; Chen, Ying; Stewart, Jonathan W; Hellerstein, David J; Mann, J John; McGrath, Patrick J

2017-09-01

Patients with bipolar disorder spend the most time in the depressed phase, and that phase is associated with the most morbidity and mortality. Treatment of bipolar depression lacks a test to determine who will respond to treatment. White matter disruptions have been found in bipolar disorder. Previous reports suggest that white matter disruptions may be associated with resistance to antidepressant medication, but this has never been investigated in a prospective study using a Food and Drug Administration (FDA)-approved medication. Eighteen subjects with bipolar disorder who were in a major depressive episode and off all medications were recruited. Magnetic resonance imaging was acquired using a 64-direction diffusion tensor imaging sequence on a 3T scanner. Subjects were treated with 8 weeks of open-label lurasidone. The Montgomrey-Asberg Depression Rating Scale (MADRS) was completed weekly. Tract-Based Spatial Statistics were utilized to perform a regression analysis of fractional anisotropy (FA) data with treatment outcome as assessed by percent change in MADRS as a regressor while controlling for age and sex, using a threshold of P (threshold-free cluster enhancement-corrected) <.05. FA was positively correlated with antidepressant treatment response in multiple regions of the mean FA skeleton bilaterally, including tracts in the frontal and parietal lobes. Greater disruptions in the white matter tracts in bipolar disorder were associated with poorer antidepressant response to lurasidone. The disruptions may potentially indicate treatment with a different antidepressant medication class. These results are limited by the open-label study design, sample size and lack of a healthy control group. © 2017 John Wiley & Sons A/S. Published by John Wiley & Sons Ltd.

Construct validity of the Heart Failure Screening Tool (Heart-FaST) to identify heart failure patients at risk of poor self-care: Rasch analysis.

PubMed

Reynolds, Nicholas A; Ski, Chantal F; McEvedy, Samantha M; Thompson, David R; Cameron, Jan

2018-02-14

The aim of this study was to psychometrically evaluate the Heart Failure Screening Tool (Heart-FaST) via: (1) examination of internal construct validity; (2) testing of scale function in accordance with design; and (3) recommendation for change/s, if items are not well adjusted, to improve psychometric credential. Self-care is vital to the management of heart failure. The Heart-FaST may provide a prospective assessment of risk, regarding the likelihood that patients with heart failure will engage in self-care. Psychometric validation of the Heart-FaST using Rasch analysis. The Heart-FaST was administered to 135 patients (median age = 68, IQR = 59-78 years; 105 males) enrolled in a multidisciplinary heart failure management program. The Heart-FaST is a nurse-administered tool for screening patients with HF at risk of poor self-care. A Rasch analysis of responses was conducted which tested data against Rasch model expectations, including whether items serve as unbiased, non-redundant indicators of risk and measure a single construct and that rating scales operate as intended. The results showed that data met Rasch model expectations after rescoring or deleting items due to poor discrimination, disordered thresholds, differential item functioning, or response dependence. There was no evidence of multidimensionality which supports the use of total scores from Heart-FaST as indicators of risk. Aggregate scores from this modified screening tool rank heart failure patients according to their "risk of poor self-care" demonstrating that the Heart-FaST items constitute a meaningful scale to identify heart failure patients at risk of poor engagement in heart failure self-care. © 2018 John Wiley & Sons Ltd.

Testing the CaR-FA-X model: investigating the mechanisms underlying reduced autobiographical memory specificity in individuals with and without a history of depression.

PubMed

Sumner, Jennifer A; Mineka, Susan; Adam, Emma K; Craske, Michelle G; Vrshek-Schallhorn, Suzanne; Wolitzky-Taylor, Kate; Zinbarg, Richard E

2014-08-01

Reduced autobiographical memory specificity (AMS) is an important cognitive phenomenon in major depressive disorder (MDD), but knowledge about mechanisms is lacking. The CaR-FA-X model of Williams and colleagues (2007) proposed that 3 processes contributed to reduce AMS: capture and rumination (CaR), functional avoidance (FA), and impaired executive control (X). However, the entire CaR-FA-X model has not been tested. We addressed this gap in the literature by investigating contributions of the CaR-FA-X mechanisms to reduced AMS, alone or in interaction, in a subset of young adults (N = 439) from the Northwestern-UCLA Youth Emotion Project. Participants were classified as those with (n = 164) and without (n = 275) a history of MDD at AMS assessment. They completed measures of: AMS; rumination (the brooding factor; CaR); childhood, adolescent, and early adulthood adversity (FA); avoidant coping (FA); and verbal fluency (X). Using structural equation modeling, we found greatest support for associations between reduced AMS and the capture and rumination, and impaired executive control mechanisms. In those with and without a history of MDD, brooding and verbal fluency interacted to contribute to reduced AMS. For participants without a history of MDD, lower verbal fluency (indicating impaired executive control) was associated with reduced AMS among those high on brooding. For participants with a history of MDD, lower verbal fluency was associated with reduced AMS among those low on brooding. The first finding was consistent with the CaR-FA-X model but the latter was not. Implications for conceptualizations of reduced AMS and its mechanisms are discussed. (c) 2014 APA, all rights reserved.

Fanconi anemia founder mutation in Macedonian patients.

PubMed

Madjunkova, Svetlana; Kocheva, Svetlana A; Plaseska-Karanfilska, Dijana

2014-01-01

Fanconi anemia (FA) is a rare autosomal recessive disorder clinically characterized by developmental abnormalities, progressive bone marrow failure (BMF) and profound cancer predisposition. Approximately 65% of all affected individuals have mutation in the FANCA (Fanconi anemia complementation group A) gene. The mutation spectrum of the FANCA gene is highly heterogeneous. FA-A is usually associated with private FANCA mutations in individual families. We describe 3 unrelated patients with FA with a similar clinical presentation: BMF, renal anomalies and café-au-lait pigmentation without major skeletal abnormality. The molecular analysis of the FANCA gene using the FA MLPA kit P031-A2/P032 FANCA, showed homozygous deletion of exon 3 in all 3 patients. Molecular analysis of the flanking regions of exon 3 precisely defined unique deletion of 2,040 bp and duplication of C (1788_3828dupC). These are the first 3 patients homozygous for deletion of FANCA exon 3 described to date. Although not related, the patients originated from the same Gypsy-like ethnic population. We conclude that c.190-256_283 + 1680del2040 dupC mutation in the FANCA gene is a founder mutation in Macedonian FA patients of Gypsy-like ethnic origin. Our finding has very strong implications for these patients in formulating diagnostic and carrier-screening strategy for BMF and FA and to enable comprehensive genetic counseling. © 2013 S. Karger AG, Basel.

Incidence of Fanconi anaemia in phenotypically normal aplastic anaemia patients in West Bengal.

PubMed

Dutta, Atreyee; De, Rajib; Dolai, Tuphan Kanti; Pal, Pritha; Ghosh, Shanoli; Mitra, Pradip Kumar; Halder, Ajanta

2018-01-07

Fanconi anaemia (FA) is a rare inherited bone marrow failure and autosomal recessive blood disorder. FA patients have a higher risk of cancer, including acute myeloid leukaemia and squamous cell carcinoma. Maximum, but not all, affected individuals have one or more somatic abnormalities, including skin, skeletal, genitourinary, gastrointestinal, cardiac and neurological anomalies, etc. Positive stress cytogenetics has immense implications for the treatment and management of FA. The aim of our study was to find out the incidence of FA in the population of phenotypically normal aplastic anaemia (AA) patients in West Bengal. Ethical clearances were obtained from the corresponding institutional committees. A total of 117 AA cases was selected. Stress cytogenetics was performed from peripheral venous blood (PVB) samples of 63 AA patients (age ≤ 50 years) and 63 age- and sex-matched healthy individual (control) using Mitomycin C (MMC). Out of 63 AA patients, 6 (9.25%) cases showed positive stress cytogenetics suggestive of FA, which is statistically significant (p-value - 0.000532), analysed by chi-square test. A considerable percentage of patients showing sensitivity towards MMC, even if they are phenotypically normal and did not have any distinguishable features which are generally found in FA. This observation may indicate that stress cytogenetics analysis of phenotypically normal AA patients (≤50 years) is essential for the improvement of the treatment procedure.

Loss of the homologous recombination gene rad51 leads to Fanconi anemia-like symptoms in zebrafish.

PubMed

Botthof, Jan Gregor; Bielczyk-Maczyńska, Ewa; Ferreira, Lauren; Cvejic, Ana

2017-05-30

RAD51 is an indispensable homologous recombination protein, necessary for strand invasion and crossing over. It has recently been designated as a Fanconi anemia (FA) gene, following the discovery of two patients carrying dominant-negative mutations. FA is a hereditary DNA-repair disorder characterized by various congenital abnormalities, progressive bone marrow failure, and cancer predisposition. In this report, we describe a viable vertebrate model of RAD51 loss. Zebrafish rad51 loss-of-function mutants developed key features of FA, including hypocellular kidney marrow, sensitivity to cross-linking agents, and decreased size. We show that some of these symptoms stem from both decreased proliferation and increased apoptosis of embryonic hematopoietic stem and progenitor cells. Comutation of p53 was able to rescue the hematopoietic defects seen in the single mutants, but led to tumor development. We further demonstrate that prolonged inflammatory stress can exacerbate the hematological impairment, leading to an additional decrease in kidney marrow cell numbers. These findings strengthen the assignment of RAD51 as a Fanconi gene and provide more evidence for the notion that aberrant p53 signaling during embryogenesis leads to the hematological defects seen later in life in FA. Further research on this zebrafish FA model will lead to a deeper understanding of the molecular basis of bone marrow failure in FA and the cellular role of RAD51.

Fanconi anaemia in South Africa: Past, present and future.

PubMed

Feben, C; Wainstein, T; Kromberg, J; Essop, F; Krause, A

2018-04-25

Fanconi anaemia (FA) is an inherited genetic disorder characterised by somatic anomalies, bone marrow failure and an increased predisposition to solid tumours and haematological malignancies. South African (SA) black and Afrikaner individuals are at higher than average risk for this condition owing to genetic founder mutations in certain Fanconi-associated genes. This review explores the epidemiology, clinical presentation, diagnostic modalities and recommended care of affected patients, focusing on the founder population groups in SA. The early diagnosis of FA is important and provides improved opportunities for early intervention, but remains challenging.

Adsorption of Eu(III) onto TiO2: effect of pH, concentration, ionic strength and soil fulvic acid.

PubMed

Tan, Xiaoli; Fang, Ming; Li, Jiaxing; Lu, Yi; Wang, Xiangke

2009-08-30

The effects of pH, initial Eu(III) concentration, ionic strength and fulvic acid (FA) on the adsorption of Eu(III) on TiO(2) are investigated by using batch techniques. The results indicate that the presence of FA strongly enhances the adsorption of Eu(III) on TiO(2) at low pH values. Besides, the adsorption of Eu(III) on TiO(2) is significantly dependent on pH values and independent of ionic strength. The adsorption of Eu(III) on TiO(2) is attributed to inner-sphere surface complexation. The diffuse layer model (DLM) is applied to simulate the adsorption data, and fits the experimental data well with the aid of FITEQL 3.2. X-ray photoelectron spectroscopy (XPS) is performed to study the species of Eu(III) adsorbed on the surfaces of TiO(2)/FA-TiO(2) hybrids at a molecular level, which suggest that FA act as "bridge" between Eu(III) and TiO(2) particles to enhance the ability to adsorb Eu(III) in solution.

Development of fluorapatite cement for dental enamel defects repair.

PubMed

Wei, Jie; Wang, Jiecheng; Shan, Wenpeng; Liu, Xiaochen; Ma, Jian; Liu, Changsheng; Fang, Jing; Wei, Shicheng

2011-06-01

In order to restore the badly carious lesion of human dental enamel, a crystalline paste of fluoride substituted apatite cement was synthesized by using the mixture of tetracalcium phosphate (TTCP), dicalcium phosphate anhydrous (DCPA) and ammonium fluoride. The apatite cement paste could be directly filled into the enamel defects (cavities) to repair damaged dental enamel. The results indicated that the hardened cement was fluorapatite [Ca(10)(PO(4))(6)F(2), FA] with calcium to phosphorus atom molar ratio (Ca/P) of 1.67 and Ca/F ratio of 5. The solubility of FA cement in Tris-HCl solution (pH = 5) was slightly lower than the natural enamel, indicating the FA cement was much insensitive to the weakly acidic solutions. The FA cement was tightly combined with the enamel surface, and there was no obvious difference of the hardness between the FA cement and natural enamel. The extracts of FA cement caused no cytotoxicity on L929 cells, which satisfied the relevant criterion on dental biomaterials, revealing good cytocompatibility. In addition, the results showed that the FA cement had good mechanical strength, hydrophilicity, and anti-bacterial adhesion properties. The study suggested that using FA cement was simple and promising approach to effectively and conveniently restore enamel defects.

Characterization nano crystalline cellulose from sugarcane baggase for reinforcement in polymer composites: Effect of formic acid concentrations

NASA Astrophysics Data System (ADS)

Aprilia, N. A. S.; Mulyati, S.; Alam, P. N.; Karmila; Ambarita, A. C.

2018-04-01

Nanocellulose from sugarcane bagasse for reinforcement in polymer composites has isolated from formic acid (FA) with different concentration. This research was conducted with three level concentration of FA ei. 15, 30 and 50%. The nanocellulose were successfully prepared with variations of total yields of 66.66, 67.33 and 69.33% respectively with increase of FA concentrations at 6 hours of hidrolysis time. The obtained nanocellulose were characterized by fourier transform infrared (FT-IR) spectroscopy confirmed the introduction of carboxyl goups on the surface of cellulose. The X-ray diffraction (XRD) spectra proved the existence of cellulose, with a highly crystalline of 62.466, 71.033, and 76.296% with increase of FA concentrations. The size of crystallinity of nanocellulose were decreased with increased of FA concentration. The result investigated that size of crystallinity of nano cellulose reduced from 4.37, 4.15 and 3.94 nm.

Exploration of microstructural abnormalities in borderline personality disorder

NASA Astrophysics Data System (ADS)

Fritzsche, Klaus H.; Brunner, Romuald; Henze, Romy; Meinzer, Hans-Peter; Stieltjes, Bram

2012-03-01

As with other mental disorders, the causes of borderline personality disorder (BPD) are complex and not fully understood. In this study we aimed to determine whether adults with BPD exhibit microstructural abnormalities using diffusion tensor imaging (DTI). 56 female right-handed individuals (age range, 14-18 years), 19 with a DSM-IV diagnosis of BPD, 18 patients with a DSM-IV defined current psychiatric disorder and 19 healthy control subjects were included. Groups were matched for age and IQ. DTI Images were analyzed using Tract-Based Spatial Statistics (TBSS). The analysis revealed significanty reduced fractional anisotropy (FA) values in the group of BPD patients compared to the normal controls. Similar FA reductions could not be found comparing BPD patients to clinical controls. Several clusters of increased radial (DR), axial (DA), and mean (MD) diffusivity were consistently identified when comparing the BPD patients to clinical as well as to healthy controls. None of the measures showed significant differences between the clinical and healthy controls. Diverse possible factors have been suggested to play a role in the disease, including environmental factors, neurobiological factors, or brain abnormalities. The presented results may play an important role in this ongoing debate.

Fuel blends: Enhanced electro-oxidation of formic acid in its blend with methanol at platinum nanoparticles modified glassy carbon electrodes

NASA Astrophysics Data System (ADS)

El-Deab, Mohamed S.; El-Nagar, Gumaa A.; Mohammad, Ahmad M.; El-Anadouli, Bahgat E.

2015-07-01

The current study addresses, for the first time, the enhanced direct electro-oxidation of formic acid (FA) at platinum-nanoparticles modified glassy carbon (nano-Pt/GC) electrode in the presence of methanol (MeOH) as a blending fuel. This enhancement is probed by: (i) the increase of the direct oxidation current of FA to CO2 (Ipd, dehydrogenation pathway), (ii) suppressing the dehydration pathway (Ipind, producing the poisoning intermediate CO) and (iii) a favorable negative shift of the onset potential of Ipd with increasing the mole fraction of MeOH in the blend. Furthermore, the charge of the direct FA oxidation in 0.3 M FA + 0.3 M MeOH blend is by 14 and 21times higher than that observed for 0.3 M FA and 0.3 M MeOH, respectively. MeOH is believed to adsorb at the Pt surface sites and thus disfavor the "non-faradaic" dissociation of FA (which produces the poisoning CO intermediate), i.e., MeOH induces a high CO tolerance of the Pt catalyst. The enhanced oxidation activity indicates that FA/MeOH blend is a promising fuel system.

Identification and individualized prediction of clinical phenotypes in bipolar disorders using neurocognitive data, neuroimaging scans and machine learning.

PubMed

Wu, Mon-Ju; Mwangi, Benson; Bauer, Isabelle E; Passos, Ives C; Sanches, Marsal; Zunta-Soares, Giovana B; Meyer, Thomas D; Hasan, Khader M; Soares, Jair C

2017-01-15

Diagnosis, clinical management and research of psychiatric disorders remain subjective - largely guided by historically developed categories which may not effectively capture underlying pathophysiological mechanisms of dysfunction. Here, we report a novel approach of identifying and validating distinct and biologically meaningful clinical phenotypes of bipolar disorders using both unsupervised and supervised machine learning techniques. First, neurocognitive data were analyzed using an unsupervised machine learning approach and two distinct clinical phenotypes identified namely; phenotype I and phenotype II. Second, diffusion weighted imaging scans were pre-processed using the tract-based spatial statistics (TBSS) method and 'skeletonized' white matter fractional anisotropy (FA) and mean diffusivity (MD) maps extracted. The 'skeletonized' white matter FA and MD maps were entered into the Elastic Net machine learning algorithm to distinguish individual subjects' phenotypic labels (e.g. phenotype I vs. phenotype II). This calculation was performed to ascertain whether the identified clinical phenotypes were biologically distinct. Original neurocognitive measurements distinguished individual subjects' phenotypic labels with 94% accuracy (sensitivity=92%, specificity=97%). TBSS derived FA and MD measurements predicted individual subjects' phenotypic labels with 76% and 65% accuracy respectively. In addition, individual subjects belonging to phenotypes I and II were distinguished from healthy controls with 57% and 92% accuracy respectively. Neurocognitive task variables identified as most relevant in distinguishing phenotypic labels included; Affective Go/No-Go (AGN), Cambridge Gambling Task (CGT) coupled with inferior fronto-occipital fasciculus and callosal white matter pathways. These results suggest that there may exist two biologically distinct clinical phenotypes in bipolar disorders which can be identified from healthy controls with high accuracy and at an individual subject level. We suggest a strong clinical utility of the proposed approach in defining and validating biologically meaningful and less heterogeneous clinical sub-phenotypes of major psychiatric disorders. Copyright © 2016 Elsevier Inc. All rights reserved.

Modification of EEG functional connectivity and EEG power spectra in overweight and obese patients with food addiction: An eLORETA study.

PubMed

Imperatori, Claudio; Fabbricatore, Mariantonietta; Innamorati, Marco; Farina, Benedetto; Quintiliani, Maria Isabella; Lamis, Dorian A; Mazzucchi, Edoardo; Contardi, Anna; Vollono, Catello; Della Marca, Giacomo

2015-12-01

We evaluated the modifications of electroencephalographic (EEG) power spectra and EEG connectivity in overweight and obese patients with elevated food addiction (FA) symptoms. Fourteen overweight and obese patients (3 men and 11 women) with three or more FA symptoms and fourteen overweight and obese patients (3 men and 11 women) with two or less FA symptoms were included in the study. EEG was recorded during three different conditions: 1) five minutes resting state (RS), 2) five minutes resting state after a single taste of a chocolate milkshake (ML-RS), and 3) five minutes resting state after a single taste of control neutral solution (N-RS). EEG analyses were conducted by means of the exact Low Resolution Electric Tomography software (eLORETA). Significant modification was observed only in the ML-RS condition. Compared to controls, patients with three or more FA symptoms showed an increase of delta power in the right middle frontal gyrus (Brodmann Area [BA] 8) and in the right precentral gyrus (BA 9), and theta power in the right insula (BA 13) and in the right inferior frontal gyrus (BA 47). Furthermore, compared to controls, patients with three or more FA symptoms showed an increase of functional connectivity in fronto-parietal areas in both the theta and alpha band. The increase of functional connectivity was also positively associated with the number of FA symptoms. Taken together, our results show that FA has similar neurophysiological correlates of other forms of substance-related and addictive disorders suggesting similar psychopathological mechanisms.

Collateral ligament (CL) injury - aftercare

MedlinePlus

... Disorders, Pain, and Rehabilitation . 3rd ed. Philadelphia, PA: Elsevier Saunders; 2015:chap 66. Miller RH, Azar FM. ... eds. Campbell's Operative Orthopaedics . 13th ed. Philadelphia, PA: Elsevier; 2017:chap 45. Niska JA, Petrigliano FA, McAllister ...

Hematological consequences of a FANCG founder mutation in Black South African patients with Fanconi anemia.

PubMed

Feben, Candice; Kromberg, Jennifer; Wainwright, Rosalind; Stones, David; Poole, Janet; Haw, Tabitha; Krause, Amanda

2015-03-01

Fanconi anemia (FA) is a rare disorder of DNA repair, associated with various somatic abnormalities but characterized by hematological disease that manifests as bone marrow aplasia and malignancy. The mainstay of treatment, in developed nations, is hematopoietic stem cell transplantation (HSCT) with subsequent surveillance for solid organ and non-hematological malignancies. In South Africa, FA in the Black population is caused by a homozygous deletion mutation in the FANCG gene in more than 80% of cases. Many affected patients are not diagnosed until late in the disease course when severe cytopenia and bone marrow aplasia are already present. Most patients are not eligible for HSCT at this late stage of the disease, even when it is available in the state health care system. In this study, the hematological presentation and disease progression in 30 Black South African patients with FA, confirmed to have the FANCG founder mutation, were evaluated and compared to those described in other FA cohorts. Our results showed that patients, homozygous for the FANCG founder mutation, present with severe cytopenia but progress to bone marrow failure at similar ages to other individuals affected with FA of heterogeneous genotype. Further, the incidence of myelodysplastic syndrome is similar to that which has been previously described in other FA cohorts. Although severe cytopenia at presentation may be predicted by a higher number of somatic anomalies, the recognition of the physical FA phenotype in Black South African patients is challenging and may not be useful in expediting referral of suspected FA patients for tertiary level investigations and care. Given the late but severe hematological presentation of FA in Black South African patients, an investigative strategy is needed for earlier recognition of affected individuals to allow for possible HSCT and management of bone marrow disease. Copyright © 2014 Elsevier Inc. All rights reserved.

Loss of Dependence on Continued Expression of the Human Papillomavirus 16 E7 Oncogene in Cervical Cancers and Precancerous Lesions Arising in Fanconi Anemia Pathway-Deficient Mice

PubMed Central

Park, Soyeong; Park, Jung Wook; Pitot, Henry C.

2016-01-01

ABSTRACT   Fanconi anemia (FA) is a rare genetic disorder caused by defects in DNA damage repair. FA patients often develop squamous cell carcinoma (SCC) at sites where high-risk human papillomaviruses (HPVs) are known to cause cancer, including the cervix. However, SCCs found in human FA patients are often HPV negative, even though the majority of female FA patients with anogenital cancers had preexisting HPV-positive dysplasia. We hypothesize that HPVs contribute to the development of SCCs in FA patients but that the continued expression of HPV oncogenes is not required for the maintenance of the cancer state because FA deficiency leads to an accumulation of mutations in cellular genes that render the cancer no longer dependent upon viral oncogenes. We tested this hypothesis, making use of Bi-L E7 transgenic mice in which we temporally controlled expression of HPV16 E7, the dominant viral oncogene in HPV-associated cancers. As seen before, the persistence of cervical neoplastic disease was highly dependent upon the continued expression of HPV16 E7 in FA-sufficient mice. However, in mice with FA deficiency, cervical cancers persisted in a large fraction of the mice after HPV16 E7 expression was turned off, indicating that these cancers had escaped from their dependency on E7. Furthermore, the severity of precancerous lesions also failed to be reduced significantly in the mice with FA deficiency upon turning off expression of E7. These findings confirm our hypothesis and may explain the fact that, while FA patients have a high frequency of infections by HPVs and HPV-induced precancerous lesions, the cancers are frequently HPV negative. Importance   Fanconi anemia (FA) patients are at high risk for developing squamous cell carcinoma (SCC) at sites where high-risk human papillomaviruses (HPVs) frequently cause cancer. Yet these SCCs are often HPV negative. FA patients have a genetic defect in their capacity to repair damaged DNA. HPV oncogenes cause an accumulation of DNA damage. We hypothesize, therefore, that DNA damage induced by HPV leads to an accumulation of mutations in patients with FA deficiency and that such mutations allow HPV-driven cancers to become independent of the viral oncogenes. Consistent with this hypothesis, we found that cervical cancers arising in HPV16 transgenic mice with FA deficiency frequently escape from dependency on the HPV16 oncogene that drove its development. Our report provides further support for vaccination of FA patients against HPVs and argues for the need to define mutational profiles of SCCs arising in FA patients in order to inform precision medicine-based approaches to treating these patients. PMID:27190216

Loss of Dependence on Continued Expression of the Human Papillomavirus 16 E7 Oncogene in Cervical Cancers and Precancerous Lesions Arising in Fanconi Anemia Pathway-Deficient Mice.

PubMed

Park, Soyeong; Park, Jung Wook; Pitot, Henry C; Lambert, Paul F

2016-05-17

Fanconi anemia (FA) is a rare genetic disorder caused by defects in DNA damage repair. FA patients often develop squamous cell carcinoma (SCC) at sites where high-risk human papillomaviruses (HPVs) are known to cause cancer, including the cervix. However, SCCs found in human FA patients are often HPV negative, even though the majority of female FA patients with anogenital cancers had preexisting HPV-positive dysplasia. We hypothesize that HPVs contribute to the development of SCCs in FA patients but that the continued expression of HPV oncogenes is not required for the maintenance of the cancer state because FA deficiency leads to an accumulation of mutations in cellular genes that render the cancer no longer dependent upon viral oncogenes. We tested this hypothesis, making use of Bi-L E7 transgenic mice in which we temporally controlled expression of HPV16 E7, the dominant viral oncogene in HPV-associated cancers. As seen before, the persistence of cervical neoplastic disease was highly dependent upon the continued expression of HPV16 E7 in FA-sufficient mice. However, in mice with FA deficiency, cervical cancers persisted in a large fraction of the mice after HPV16 E7 expression was turned off, indicating that these cancers had escaped from their dependency on E7. Furthermore, the severity of precancerous lesions also failed to be reduced significantly in the mice with FA deficiency upon turning off expression of E7. These findings confirm our hypothesis and may explain the fact that, while FA patients have a high frequency of infections by HPVs and HPV-induced precancerous lesions, the cancers are frequently HPV negative. IMPORTANCE  : Fanconi anemia (FA) patients are at high risk for developing squamous cell carcinoma (SCC) at sites where high-risk human papillomaviruses (HPVs) frequently cause cancer. Yet these SCCs are often HPV negative. FA patients have a genetic defect in their capacity to repair damaged DNA. HPV oncogenes cause an accumulation of DNA damage. We hypothesize, therefore, that DNA damage induced by HPV leads to an accumulation of mutations in patients with FA deficiency and that such mutations allow HPV-driven cancers to become independent of the viral oncogenes. Consistent with this hypothesis, we found that cervical cancers arising in HPV16 transgenic mice with FA deficiency frequently escape from dependency on the HPV16 oncogene that drove its development. Our report provides further support for vaccination of FA patients against HPVs and argues for the need to define mutational profiles of SCCs arising in FA patients in order to inform precision medicine-based approaches to treating these patients. Copyright © 2016 Park et al.

Thermal surface analysis on high-rise building façades with neo-minimalist and modern style in Penang, Malaysia

NASA Astrophysics Data System (ADS)

Arab, Yasser; Hassan, Ahmad Sanusi; Qanaa, Bushra

2017-10-01

This research analyzed the façade thermal performance of high-rise buildings with modern and neo-minimalist architectural style. Four high-rise apartment buildings in Penang Island are selected as case studies for this research. The modern architectural style, which was popular during the 1970s to 1990s, nearly disregarded the cultural identity of the country and used the basic geometric shapes in the design. Conversely, the neo-minimalist style is the popular style from the 2010s up to the present. This style is a result of the "less is more" concept, which means using minimal applications to obtain an efficient design. The four selected case studies are as follows: Halaman Kristal 2 and Mutiara Idaman 1 with modern architectural style and Light Linear and Baystar apartments with neo-minimalist style. The research uses Fluke Ti20 thermal imager to capture thermal images of the west façade of the selected case studies on an hourly basis from 12:00 to 6:00 P.M. on March 15, 2017. Results confirm that the neo-minimalist façade elements, such as balconies and recessed walls, as well as other shading elements, are effective in improving the performance of façade shading. Notably, façade shading causes low surface temperature and provides cool indoor atmosphere during the day when the temperature is extremely high outside. Accordingly, this distinct feature partly explains the current popularity of the neo-minimalist architectural style.

Myeloperoxidase-derived 2-chlorofatty acids contribute to human sepsis mortality via acute respiratory distress syndrome.

PubMed

Meyer, Nuala J; Reilly, John P; Feng, Rui; Christie, Jason D; Hazen, Stanley L; Albert, Carolyn J; Franke, Jacob D; Hartman, Celine L; McHowat, Jane; Ford, David A

2017-12-07

Sepsis-associated acute respiratory distress syndrome (ARDS) is characterized by neutrophilic inflammation and poor survival. Since neutrophil myeloperoxidase (MPO) activity leads to increased plasma 2-chlorofatty acid (2-ClFA) levels, we hypothesized that plasma concentrations of 2-ClFAs would associate with ARDS and mortality in subjects with sepsis. In sequential consenting patients with sepsis, free 2-ClFA levels were significantly associated with ARDS, and with 30-day mortality, for each log increase in free 2-chlorostearic acid. Plasma MPO was not associated with either ARDS or 30-day mortality but was correlated with 2-ClFA levels. Addition of plasma 2-ClFA levels to the APACHE III score improved prediction for ARDS. Plasma 2-ClFA levels correlated with plasma levels of angiopoietin-2, E selectin, and soluble thrombomodulin. Endothelial cells treated with 2-ClFA responded with increased adhesion molecule surface expression, increased angiopoietin-2 release, and dose-dependent endothelial permeability. Our results suggest that 2-ClFAs derived from neutrophil MPO-catalyzed oxidation contribute to pulmonary endothelial injury and have prognostic utility in sepsis-associated ARDS.

Environmentally friendly, one-pot synthesis of folic acid-decorated graphene oxide-based drug delivery system

NASA Astrophysics Data System (ADS)

Lin, Quankui; Huang, Xiaojie; Tang, Junmei; Han, Yuemei; Chen, Hao

2013-12-01

A targeted drug delivery system based on graphene oxide (GO) was produced via one-pot synthesis method, taking advantages of the self-polymerization of the dopamine (DA). The polymerization of dopamine resulted in polydopamine capped GO nanocomposite. Meanwhile, the anti-tumor drug doxorubicin (DOX) can be loaded in the nanocomposite and the tumor cell targeting molecule folic acid (FA) can also been immobilized on the nanocomposite surface simultaneously. The size of the obtained FA-decorated GO-based drug delivery system (DA/GO(DOX)-FA) is about 600 nm. It renders a sustained drug release manner. The cell culture results reveal that the FA-decorated GO-based drug delivery system (DA/GO(DOX)-FA) via one-pot method shows property of targeted killing of cancer cells in vitro. This one-pot method just needs the pH adjusting to induce the self-polymerization of DA, but excludes the fussy chemical grafting process and the organic solvents, which make it an environmentally friendly method to synthesize FA-decorated GO-based drug delivery system.

A pre-protective strategy for precise tumor targeting and efficient photodynamic therapy with a switchable DNA/upconversion nanocomposite.

PubMed

Yu, Zhengze; Ge, Yegang; Sun, Qiaoqiao; Pan, Wei; Wan, Xiuyan; Li, Na; Tang, Bo

2018-04-14

Tumor-specific targeting based on folic acid (FA) is one of the most common and significant approaches in cancer therapy. However, the expression of folate receptors (FRs) in normal tissues will lead to unexpected targeting and unsatisfactory therapeutic effect. To address this issue, we develop a pre-protective strategy for precise tumor targeting and efficient photodynamic therapy (PDT) using a switchable DNA/upconversion nanocomposite, which can be triggered in the acidic tumor microenvironment. The DNA/upconversion nanocomposite is composed of polyacrylic acid (PAA) coated upconversion nanoparticles (UCNPs), the surface of which is modified using FA and chlorin e6 (Ce6) functionalized DNA sequences with different lengths. Initially, FA on the shorter DNA was protected by a longer DNA to prevent the bonding to FRs on normal cells. Once reaching the acidic tumor microenvironment, C base-rich longer DNA forms a C-quadruplex, resulting in the exposure of the FA groups and the bonding of FA and FRs on cancer cell membranes to achieve precise targeting. Simultaneously, the photosensitizer chlorin e6 (Ce6) gets close to the surface of UCNPs, enabling the excitation of Ce6 to generate singlet oxygen ( 1 O 2 ) under near infrared light via Förster resonance energy transfer (FRET). In vivo experiments indicated that higher tumor targeting efficiency was achieved and the tumor growth was greatly inhibited through the pre-protective strategy.

Injectable, in situ forming poly(propylene fumarate)-based ocular drug delivery systems.

PubMed

Ueda, H; Hacker, M C; Haesslein, A; Jo, S; Ammon, D M; Borazjani, R N; Kunzler, J F; Salamone, J C; Mikos, A G

2007-12-01

This study sought to develop an injectable formulation for long-term ocular delivery of fluocinolone acetonide (FA) by dissolving the anti-inflammatory drug and the biodegradable polymer poly(propylene fumarate) (PPF) in the biocompatible, water-miscible, organic solvent N-methyl-2-pyrrolidone (NMP). Upon injection of the solution into an aqueous environment, a FA-loaded PPF matrix is precipitated in situ through the diffusion/extraction of NMP into surrounding aqueous fluids. Fabrication of the matrices and in vitro release studies were performed in phosphate buffered saline at 37 degrees C. Drug loadings up to 5% were achieved. High performance liquid chromatography was employed to determine the released amount of FA. The effects of drug loading, PPF content of the injectable formulation, and additional photo-crosslinking of the matrix surface were investigated. Overall, FA release was sustained in vitro over up to 400 days. After an initial burst release of 22 to 68% of initial FA loading, controlled drug release driven by diffusion and bulk erosion was observed. Drug release rates in a therapeutic range were demonstrated. Release kinetics were found to be dependent on drug loading, formulation PPF content, and extent of surface crosslinking. The results suggest that injectable, in situ formed PPF matrices are promising candidates for the formulation of long-term, controlled delivery devices for intraocular drug delivery. Copyright 2007 Wiley Periodicals, Inc.

Effect of different carboxylic acids in cyclodextrin functionalization of cellulose nanocrystals for prolonged release of carvacrol.

PubMed

Castro, D O; Tabary, N; Martel, B; Gandini, A; Belgacem, N; Bras, J

2016-12-01

Current investigations deal with new surface functionalization strategy of nanocrystalline cellulose-based substrates to impart active molecule release properties. In this study, cellulose nanocrystals (CNC) were surface-functionalized with β-cyclodextrin (β-CD) using succinic acid (SA) and fumaric acid (FA) as bridging agents. The main objective of this surface modification performed only in aqueous media was to obtain new active materials able to release antibacterial molecules over a prolonged period of time. The reactions were conducted by immersing the CNC film into a solution composed of β-CD, SA and FA, leading to CNC grafting. The materials were characterized by infrared spectroscopy (FT-IR), Quartz crystal microbalance-dissipation (QCM-D), AFM and phenolphthalein (PhP) was used to determine the efficiency of CNC grafting with β-CD. The results indicated that β-CD was successfully attached to the CNC backbone through the formation of ester bonds. Furthermore, carvacrol was entrapped by the attached β-CD and a prolonged release was confirmed. In particular, CNC grafted to β-CD in the presence of FA was selected as the best solution. The antibacterial activity and the controlled release were studied for this sample. Considerably longer bacterial activity against B. subtilis was observed for CNC grafted to β-CD compared to CNC and CNC-FA, confirming the promising impact of the present strategy. Copyright © 2016 Elsevier B.V. All rights reserved.

Development of LSPR and SPR sensor for the detection of an anti-cancer drug for chemotherapy

NASA Astrophysics Data System (ADS)

Zhao, Sandy Shuo; Bolduc, Olivier R.; Colin, Damien Y.; Pelletier, Joelle N.; Masson, Jean-François

2012-03-01

The anti-cancer drug, methotrexate (MTX) as a strong inhibitor of human dihydrofolate reductase (hDHFR) has been studied in localized surface plasmon resonance (LSPR) and surface plasmon resonance (SPR) competitive binding assays with folic acid stabilized gold nanoparticles (FA AuNP). The latter with a diameter of 15 nm were prepared in a simple step with sequential characterization using UV-Vis, FTIR, and Raman. A LSPR competitive binding assay between different concentrations of MTX and FA AuNP for hDHFR in solution was designed to quantify MTX by using UV-Vis spectroscopy. Sensitivity of the assay was optimized with respect to both concentrations of the enzyme and FA. The detection and quantification of spiked MTX was demonstrated in phosphate buffer saline and in fetal bovine serum accompanied by solid-phase extraction treatment of the serum. In addition, this assay could also provide as a screening tool for potential inhibitors of hDHFR. In another perspective, MTX was measured in a competitive binding assay with FA AuNP for histidine-tagged hDHFR immobilized on a SPR sensitive surface. In this case, FA AuNP offer a secondary amplification of the analytical response which is indirectly proportional to the concentration of MTX. This alternative approach could contribute to the realization of direct detection of MTX in complex biological fluids. A comparison of characteristics and analytical parameters such as sensitivity, dynamic range and limit of detection between the LSPR and SPR sensing platforms will also be presented. Both assays offer potential in tackling real biological samples for the purpose of monitoring and validating anti-cancer drug levels in human serum during chemotherapy.

High frequency of exon 15 deletion in the FANCA gene in Tunisian patients affected with Fanconi anemia disease: implication for diagnosis.

PubMed

Amouri, Ahlem; Talmoudi, Faten; Messaoud, Olfa; d'Enghien, Catherine D; Rekaya, Mariem B; Allegui, Ines; Azaiez, Héla; Kefi, Rym; Abdelhak, Ahlem; Meseddi, Sondes H; Torjemane, Lamia; Ouederni, Monia; Mellouli, Fethi; Abid, Héla B; Aissaoui, Lamia; Bejaoui, Mohamed; Othmen, Tarek B; Lyonnet, Dominique S; Soulier, Jean; Hachicha, Mongia; Dellagi, Koussay; Abdelhak, Sonia; Fanconi, Tunisian

2014-03-01

Tunisian population is characterized by its heterogeneous ethnic background and high rate of consanguinity. In consequence, there is an increase in the frequency of recessive genetic disorders including Fanconi anemia (FA). The aim of this study was to confirm the existence of a founder haplotype among FA Tunisian patients and to identify the associated mutation in order to develop a simple tool for FA diagnosis. Seventy-four unrelated families with a total of 95 FA patients were investigated. All available family members were genotyped with four microsatellite markers flanking FANCA gene. Haplotype analysis and homozygosity mapping assigned 83 patients belonging to 62 families to the FA-A group. A common haplotype was shared by 42 patients from 26 families at a homozygous state while five patients from five families were heterozygous. Among them, 85% were from southern Tunisia suggesting a founder effect. Using multiplex ligation-dependent probe amplification (MLPA) technique, we have also demonstrated that this haplotype is associated with a total deletion of exon 15 in FANCA gene. Identification of a founder mutation allowed genetic counseling in relatives of these families, better bone marrow graft donor selection and prenatal diagnosis. This mutation should be investigated in priority for patients originating from North Africa and Middle East.

High frequency of exon 15 deletion in the FANCA gene in Tunisian patients affected with Fanconi anemia disease: implication for diagnosis

PubMed Central

Amouri, Ahlem; Talmoudi, Faten; Messaoud, Olfa; d'Enghien, Catherine D; Rekaya, Mariem B; Allegui, Ines; Azaiez, Héla; Kefi, Rym; Abdelhak, Ahlem; Meseddi, Sondes H; Torjemane, Lamia; Ouederni, Monia; Mellouli, Fethi; Abid, Héla B; Aissaoui, Lamia; Bejaoui, Mohamed; Othmen, Tarek B; Lyonnet, Dominique S; Soulier, Jean; Hachicha, Mongia; Dellagi, Koussay; Abdelhak, Sonia; Fanconi, Tunisian

2014-01-01

Tunisian population is characterized by its heterogeneous ethnic background and high rate of consanguinity. In consequence, there is an increase in the frequency of recessive genetic disorders including Fanconi anemia (FA). The aim of this study was to confirm the existence of a founder haplotype among FA Tunisian patients and to identify the associated mutation in order to develop a simple tool for FA diagnosis. Seventy-four unrelated families with a total of 95 FA patients were investigated. All available family members were genotyped with four microsatellite markers flanking FANCA gene. Haplotype analysis and homozygosity mapping assigned 83 patients belonging to 62 families to the FA-A group. A common haplotype was shared by 42 patients from 26 families at a homozygous state while five patients from five families were heterozygous. Among them, 85% were from southern Tunisia suggesting a founder effect. Using multiplex ligation-dependent probe amplification (MLPA) technique, we have also demonstrated that this haplotype is associated with a total deletion of exon 15 in FANCA gene. Identification of a founder mutation allowed genetic counseling in relatives of these families, better bone marrow graft donor selection and prenatal diagnosis. This mutation should be investigated in priority for patients originating from North Africa and Middle East. PMID:24689079

Fibroadenomatoid mastopathy: another distractive breast lesion?

PubMed

Tan, P E; Looi, L M

1991-12-01

Although most anatomical pathologists have encountered breast lesions with the composite histological features of fibroadenoma (FA) and fibrocystic change (FC), referred to as fibroadenomatosis or fibroadenomatoid mastopathy (FAM), little is known about its prevalence or clinico-pathological significance. In a retrospective histological review of 400 consecutive breast lesions, among both East and West Malaysians, coded either as FA or FC in the files of the Department of Pathology, University of Malaya, we found 45 (11.3%) cases of FAM. Typically, FAM lesions showed fibroadenomatoid foci in a background of fibrocystic change. The finding of FAM among lesions coded as FC was higher (18.5%) than among FA (4%). The mean age of patients with FAM (32.1 years) was similar to FC (35.1 years) but significantly older than that of FA (26.1 years). The notion that FA and FC are lesions at two ends of a spectrum of growth disorder of breast related to oestrogen-progesterone interplay, and that FAM occupies a position intermediate between the two, may explain its morphological and age patterns, but remains speculative. It is hoped that increasing awareness of this condition will lead to better understanding of breast pathophysiology. Nevertheless, until its biological nature, histogenesis and malignant potential are more clearly understood, defining FAM as a distinct form of breast disease may not be meaningful to patient management.

Food allergy in dogs and cats: a review.

PubMed

Verlinden, A; Hesta, M; Millet, S; Janssens, G P J

2006-01-01

Food allergy (FA) is defined as "all immune-mediated reactions following food intake," in contrast with food intolerance (FI), which is non-immune-mediated. Impairment of the mucosal barrier and loss of oral tolerance are risk factors for the development of FA. Type I, III, and IV hypersensitivity reactions are the most likely immunologic mechanisms. Food allergens are (glyco-)proteins with a molecular weight from 10-70 kDa and are resistant to treatment with heat, acid, and proteases. The exact prevalence of FA in dogs and cats remains unknown. There is no breed, sex or age predilection, although some breeds are commonly affected. Before the onset of clinical signs, the animals have been fed the offending food components for at least two years, although some animals are less than a year old. FA is a non-seasonal disease with skin and/or gastrointestinal disorders. Pruritus is the main complaint and is mostly corticoid-resistant. In 20-30% of the cases, dogs and cats have concurrent allergic diseases (atopy/flea-allergic dermatitis). A reliable diagnosis can only be made with dietary elimination-challenge trials. Provocation testing is necessary for the identification of the causative food component(s). Therapy of FA consists of avoiding the offending food component(s).

[Food allergy, food intolerance or functional disorder?].

PubMed

Wüthrich, B

2009-04-01

The term "food allergy" is widely misused for all sorts of symptoms and diseases caused by food. Food allergy (FA) is an adverse reaction to food (food hypersensitivity) occurring in susceptible individuals, which is mediated by a classical immune mechanism specific for the food itself. The best established mechanism in FA is due to the presence of IgE antibodies against the offending food. Food intolerance (FI) are all non-immune-mediated adverse reactions to food. The subgroups of FI are enzymatic (e.g. lactose intolerance due to lactase deficiency), pharmacological (reactions against biogenic amines, histamine intolerance), and undefined food intolerance (e.g. against some food additives). The diagnosis of an IgE-mediated FA is made by a carefully taken case history, supported by the demonstration of an IgE sensitization either by skin prick tests or by in vitro tests, and confirmed by positive oral provocation. For scientific purposes the only accepted test for the confirmation of FA/FI is a properly performed double-blind, placebo-controlled food challenge (DBPCFC). A panel of recombinant allergens, produced as single allergenic molecules, may in future improve the diagnosis of IgE-mediated FA. Due to a lack of causal treatment possibilities, the elimination of the culprit "food allergen" from the diet is the only therapeutic option for patients with real food allergy.

A pilot DTI analysis in patients with recent onset post-traumatic stress disorder

NASA Astrophysics Data System (ADS)

Liu, Yang; Li, Liang; Li, Baojuan; Zhang, Xi; Lu, Hongbing

2016-03-01

To explore the alteration in white matter between survivors with recent onset post-traumatic stress disorder (PTSD) and without PTSD, who survived from the same coal mine flood disaster, the diffusion tensor imaging (DTI) sequences were analyzed using DTI studio and statistical parametric mapping (SPM) packages in this paper. From DTI sequence, the fractional anisotropy (FA) value describes the degree of anisotropy of a diffusion process, while the apparent diffusion coefficient (ADC) value reflects the magnitude of water diffusion. The DTI analyses between PTSD and non-PTSD indicate lower FA values in the right caudate nucleus, right middle temporal gyrus, right fusiform gyrus, and right superior temporal gyrus, and higher ADC values in the right superior temporal gyrus and right corpus callosum of the subjects with PTSD. These results are partly in line with our previous volume and cortical thickness analyses, indicating the importance of multi-modality analysis for PTSD.

[Brain structure analysis for patients with antisocial personality disorder by MRI].

PubMed

Jiang, Weixiong; Liao, Jian; Liu, Huasheng; Huang, Renzhi; Li, Yongfan; Wang, Wei

2015-02-01

To investigate the structural abnormalities of brain in patients with antisocial personality disorder (ASPD) but without alcoholism and drug abuse. Volunteers from Hunan Reformatory (n=36) and the matched healthy subjects (n=26) were examined by high-spatial resolution magnetic resonance imaging (MRI) and diffusion tensor imaging (DTI). Voxel-based morphometry and fractional anisotropy (FA) maps were generated for each subject to reveal structural abnormalities in patients with ASPD. Compared with the healthy controls, ASPD patients showed significantly higher gray matter volumes in the inferior parietal lobule (P≤0.001, uncorrected), white matter volumes in the precuneus (P≤0.001, uncorrected), FA in the left lingual gyrus, bilateral precuneus, right superior frontal gyrus and right middle temporal gyrus (P≤0.01, uncorrected). Our results revealed the abnormal neuroanatomical features in ASPD patients, which might be related to the external behavioral traits in ASPD patients.

Fancb deficiency impairs hematopoietic stem cell function

PubMed Central

Du, Wei; Amarachintha, Surya; Erden, Ozlem; Wilson, Andrew; Meetei, Amom Ruhikanta; Andreassen, Paul R.; Namekawa, Satoshi H.; Pang, Qishen

2015-01-01

Fanconi anemia (FA) is a genetic disorder characterized by bone marrow failure, variable congenital malformations and a predisposition to malignancies. FANCB (also known as FAAP95), is the only X-linked FA gene discovered thus far. In the present study, we investigated hematopoiesis in adult Fancb deficient (Fancb−/y) mice and found that Fancb−/y mice have decreased hematopoietic stem cell (HSC) quiescence accompanied by reduced progenitor activity in vitro and reduced repopulating capacity in vivo. Like other FA mouse models previously reported, the hematopoietic system of Fancb−/y mice is hypersensitive to DNA cross-linking agent mitomycin C (MMC), which induces bone marrow failure in Fancb−/y mice. Furthermore, Fancb−/y BM exhibits slower recovery kinetics and less tolerance to myelotoxic stress induced by 5-fluorouracil than wild-type littermates. RNA-seq analysis reveals altered expression of genes involved in HSC function and cell cycle regulation in Fancb−/y HSC and progenitor cells. Thus, this Fancb−/y mouse model provides a novel approach for studying the critical role of the FA pathway not only in germ cell development but also in the maintenance of HSC function. PMID:26658157

An Analysis of the Effects of Functional Communication and a Voice Output Communication Aid for a Child with Autism Spectrum Disorder

ERIC Educational Resources Information Center

Olive, Melissa L.; Lang, Russell B.; Davis, Tonya N.

2008-01-01

The purpose of this study was to examine the effects of Functional Communication Training (FCT) and a Voice Output Communication Aid (VOCA) on the challenging behavior and language development of a 4-year-old girl with autism spectrum disorder. The participant's mother implemented modified functional analysis (FA) and intervention procedures in…

Alterations in the inferior longitudinal fasciculus in autism and associations with visual processing: a diffusion-weighted MRI study.

PubMed

Boets, Bart; Van Eylen, Lien; Sitek, Kevin; Moors, Pieter; Noens, Ilse; Steyaert, Jean; Sunaert, Stefan; Wagemans, Johan

2018-01-01

One of the most reported neural features of autism spectrum disorder (ASD) is the alteration of multiple long-range white matter fiber tracts, as assessed by diffusion-weighted imaging and indexed by reduced fractional anisotropy (FA). Recent methodological advances, however, have shown that this same pattern of reduced FA may be an artifact resulting from excessive head motion and poorer data quality and that aberrant structural connectivity in children with ASD is confined to the right inferior longitudinal fasciculus (ILF). This study aimed at replicating the observation of reduced FA along the right ILF in ASD, while controlling for group differences in head motion and data quality. In addition, we explored associations between reduced FA in the right ILF and quantitative ASD characteristics, and the involvement of the right ILF in visual processing, which is known to be altered in ASD. Global probabilistic tractography was performed on diffusion-weighted imaging data of 17 adolescent boys with ASD and 17 typically developing boys, matched for age, performance IQ, handedness, and data quality. Four tasks were administered to measure various aspects of visual information processing, together with questionnaires assessing ASD characteristics. Group differences were examined and the neural data were integrated with previously published findings using Bayesian statistics to quantify evidence for replication and to pool data and thus increase statistical power. (Partial) correlations were calculated to investigate associations between measures. The ASD group showed consistently reduced FA only in the right ILF and slower performance on the visual search task. Bayesian statistics pooling data across studies confirmed that group differences in FA were confined to the right ILF only, with the evidence for altered FA in the left ILF being indecisive. Lower FA in the right ILF tended to covary with slower visual search and a more fragmented part-oriented processing style. Individual differences in FA of the right ILF were not reliably associated with the severity of ASD traits after controlling for clinical status. Our findings support the growing evidence for reduced FA along a specific fiber tract in ASD, the right ILF.

Tracking down the footprints of bad paternal relationships in dissociative disorders: A diffusion tensor imaging study.

PubMed

Basmacı Kandemir, Sultan; Bayazıt, Hüseyin; Selek, Salih; Kılıçaslan, Nihat; Kandemir, Hasan; Karababa, İbrahim Fatih; Katı, Mahmut; Çeçe, Hasan

2016-01-01

Preclinical studies indicate that stress early in life can cause long-term alterations in brain development. Studies have shown alterations in the brain functions of patients after experiencing trauma. Our aim is to examine whether the integrity of white matter tracts might be affected in dissociative disorder (DD) patients. A total of 15 DD patients and 15 healthy controls were studied, with the groups matched by age and gender. Diffusion-weighted echoplanar brain images were obtained using a 1.5 Tesla magnetic resonance imaging scanner. Regions of interest were manually placed on directional maps based on principal anisotropy. Apparent diffusion coefficient and fractional anisotropy (FA) values of white matter were measured bilaterally in the anterior corona radiata (ACR) and by diffusion tensor imaging in the genu and splenium of the corpus callosum. Significantly lower FA values were observed in the right ACR of DD patients versus healthy individuals. We also found an association between bad paternal relationships and lower FA in the genu of the corpus callosum in female patients. Alterations in the right ACR suggest that diffusion anisotropy measurement can be used as a quantitative biomarker for DD. Paternal relationships may also affect the brain's microstructure in women with DD.

Source apportionment of trace metals in surface waters of a polluted stream using multivariate statistical analyses.

PubMed

Pekey, Hakan; Karakaş, Duran; Bakoğlu, Mithat

2004-11-01

Surface water samples were collected from ten previously selected sites of the polluted Dil Deresi stream, during two field surveys, December 2001 and April 2002. All samples were analyzed using ICP-AES, and the concentrations of trace metals (Al, As, Ba, Cd, Co, Cr, Cu, Fe, Pb, Sn and Zn) were determined. The results were compared with national and international water quality guidelines, as well as literature values reported for similar rivers. Factor analysis (FA) and a factor analysis-multiple regression (FA-MR) model were used for source apportionment and estimation of contributions from identified sources to the concentration of each parameter. By a varimax rotated factor analysis, four source types were identified as the paint industry; sewage, crustal and road traffic runoff for trace metals, explaining about 83% of the total variance. FA-MR results showed that predicted concentrations were calculated with uncertainties lower than 15%.

Diffusion tensor imaging of anterior commissural fibers in patients with schizophrenia.

PubMed

Choi, Hongyoon; Kubicki, Marek; Whitford, Thomas J; Alvarado, Jorge L; Terry, Douglas P; Niznikiewicz, Margaret; McCarley, Robert W; Kwon, Jun Soo; Shenton, Martha E

2011-08-01

Alterations in white matter connections in schizophrenia have been investigated using diffusion tensor imaging (DTI). There is also evidence from post-mortem studies as well as from magnetic resonance imaging morphometry studies that the anterior commissure (AC) might be implicated in schizophrenia, but no studies, to date, have investigated the AC using DTI or tractography. DTI scans were analyzed from 25 patients and 23 controls. Mean fractional anisotropy (FA) and trace were measured from the AC tracts. SANS and SAPS were used to evaluate clinical symptoms, and the Iowa Gambling Task, related to decision making, was also examined. Results revealed a significant decrease in mean FA and a significant increase in mean trace of AC tracts in patients compared with controls. In addition, patients, but not controls, showed a negative correlation between age and AC integrity. Statistically significant positive correlations were also found between AC FA and total positive symptom score. Decision making was negatively correlated with FA in patients on the Iowa Gambling Task, but not in controls. This study provides quantitative evidence for a reduction of interhemispheric connectivity in schizophrenia within the AC. Negative correlation between age and AC FA in the patients is consistent with the idea that schizophrenia may be a disorder of white matter maturation. Positive correlation between FA and positive symptom is discussed in the context of white matter's established role in modulating neural conduction velocity. Published by Elsevier B.V.

Phenotypic variability in patients with Fanconi anemia and biallelic FANCF mutations.

PubMed

Tryon, Rebecca; Zierhut, Heather; MacMillan, Margaret L; Wagner, John E

2017-01-01

Fanconi anemia is a heterogeneous genetic disorder that is characterized by progressive bone marrow failure, congenital anomalies, and markedly increased risk for malignancies. Mutations in the FANCF (FA-F) gene represent approximately 2% of affected patients. Currently, information on the phenotypic findings of patients with Fanconi anemia from biallelic mutations in FANCF is limited. Here, we report three patients who illustrate the clinical variability within the FA-F group. This analysis suggests a more severe phenotype for those with the common c.484_485delCT mutation. © 2016 Wiley Periodicals, Inc. © 2016 Wiley Periodicals, Inc.

Role of cationic size in the optical properties of the LiCl crystal surface: theoretical study.

PubMed

Abdel Halim, Wael Salah; Abdullah, Noha; Abdel-Aal, Safaa; Shalabi, A S

2012-06-01

The size of the cations (either Ca(2+), Sr(2+), Ga(+), or Au(+)) at the F(A1)-type color centers on the (100) surface of LiCl crystal plays an important role in the optical properties of this surface. In this work, double-well potentials at this surface were investigated using ab initio quantum mechanical methods. Quantum clusters were embedded in simulated Coulomb fields that closely approximate the Madelung fields of the host surface, and the ions that were the nearest neighbors to the F(A1) site were allowed to relax to equilibrium. The calculated Stokes-shifted optical transition bands, optical-optical conversion efficiency, and relaxed excited states of the defect-containing surface, as well as the orientational destruction of the color centers, recording sensitivity, exciton (energy) transfer, and the Glasner-Tompkins empirical relation were all found to be sensitive to the size of the dopant cation.

Microstructural abnormalities of the brain white matter in attention-deficit/hyperactivity disorder

PubMed Central

Chen, Lizhou; Huang, Xiaoqi; Lei, Du; He, Ning; Hu, Xinyu; Chen, Ying; Li, Yuanyuan; Zhou, Jinbo; Guo, Lanting; Kemp, Graham J.; Gong, Qiyong

2015-01-01

Background Attention-deficit/hyperactivity disorder (ADHD) is an early-onset neurodevelopmental disorder with multiple behavioural problems and executive dysfunctions for which neuroimaging studies have reported a variety of abnormalities, with inconsistencies partly owing to confounding by medication and concurrent psychiatric disease. We aimed to investigate the microstructural abnormalities of white matter in unmedicated children and adolescents with pure ADHD and to explore the association between these abnormalities and behavioural symptoms and executive functions. Methods We assessed children and adolescents with ADHD and healthy controls using psychiatric interviews. Behavioural problems were rated using the revised Conners’ Parent Rating Scale, and executive functions were measured using the Stroop Colour-Word Test and the Wisconsin Card Sorting test. We acquired diffusion tensor imaging data using a 3 T MRI system, and we compared diffusion parameters, including fractional anisotropy (FA) and mean, axial and radial diffusivities, between the 2 groups. Results Thirty-three children and adolescents with ADHD and 35 healthy controls were included in our study. In patients compared with controls, FA was increased in the left posterior cingulum bundle as a result of both increased axial diffusivity and decreased radial diffusivity. In addition, the averaged FA of the cluster in this region correlated with behavioural measures as well as executive function in patients with ADHD. Limitations This study was limited by its cross-sectional design and small sample size. The cluster size of the significant result was small. Conclusion Our findings suggest that white matter abnormalities within the limbic network could be part of the neural underpinning of behavioural problems and executive dysfunction in patients with ADHD. PMID:25853285

Folate conjugated Mn{sub 3}O{sub 4}@SiO{sub 2} nanoparticles for targeted magnetic resonance imaging in vivo

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

Yang, Xinyi; Zhou, Zhiguo, E-mail: zgzhou@shnu.edu.cn; Wang, Li

2014-09-15

Graphical abstract: The Mn{sub 3}O{sub 4}@SiO{sub 2}(PEG)–FA has been used as a T{sub 1}-MRI probe for in vivo. - Highlights: • The PEG and FA modified Mn{sub 3}O{sub 4}@SiO{sub 2} nanoparticles (Mn{sub 3}O{sub 4}@SiO{sub 2}–FA) were prepared. • Mn{sub 3}O{sub 4}@SiO{sub 2}–FA exhibited the good colloidal stability in the simulated biological medium. • Mn{sub 3}O{sub 4}@SiO{sub 2}–FA showed the targeting ability to HeLa cells overexpressed the FA receptor. • The T{sub 1}-weighted magnetic resonance (MR) imaging demonstrated the targeting ability of Mn{sub 3}O{sub 4}@SiO{sub 2}–FA in vivo tumor. - Abstract: The monodisperse silica-coated manganese oxide nanoparticles (Mn{sub 3}O{sub 4}@SiO{sub 2}more » NPs) were synthesized via the high temperature pyrolysis approach and were aminated through silanization. The amine-functionalized Mn{sub 3}O{sub 4} NPs enabled the covalent conjugation of hydrophilic methoxypoly(ethylene glycol) (PEG) and the targeting ligand of folate (FA) onto their surface. The formed PEG and FA modified Mn{sub 3}O{sub 4} NPs (Mn{sub 3}O{sub 4}@SiO{sub 2}(PEG)–FA) exhibited the good colloidal stability in the simulated biological medium and the targeting ability to HeLa cells overexpressed the FA receptor. The T{sub 1}-weighted magnetic resonance (MR) imaging and inductively coupled plasma atomic emission spectroscopy (ICP-AES) analysis of Mn{sub 3}O{sub 4}@SiO{sub 2}(PEG)–FA NPs further demonstrated their targeting ability in tumor.« less

Folic acid modified Pluronic F127 coating Ag2S quantum dot for photoacoustic imaging of tumor cell-targeting

NASA Astrophysics Data System (ADS)

Zhang, Ruo-Yun; Wang, Zhao-Yang; Yang, Xiao-Quan; Xuan, Yang; Cheng, Kai; Li, Cheng; Song, Xian-Lin; An, Jie; Hou, Xiao-Lin; Zhao, Yuan-Di

2018-02-01

In this study, an oil-soluble Ag2S quantum dot (QD) was synthesized through thermal decomposition using the single-source precursor method, and Pluronic F127 (PF127), a triblock copolymer functionalized with folic acid (FA), was deposited on the surface of the QD, then a water-soluble PF127-FA@Ag2S nanoprobe with targeting ability was fabricated. The as-prepared PF127-FA@Ag2S exhibited spheroidal morphology and high dispersibility, with average diameters of 115 ± 20.7 nm (as observed by transmission electron microscopy). No obvious toxicity of the PF127-FA@Ag2S nanoprobe was found in standard 3-(4, 5-dimethylthiazol-2-yl)-2, 5-diphenyltetrazolium bromide assay and colony-formation assay, indicating good biocompatibility and safety. The resulting PF127-FA@Ag2S exhibited excellent stability between 4 °C-40 °C. Additionally, the capacity of the tumor cell-targeting high contrast enhanced photoacoustic imaging of PF127-FA@Ag2S was verified in comparison with A547 and HeLa cells. In other words, the excellent properties of PF127-FA@Ag2S show great potential in further research for targeting and photoacoustic imaging.

Studies on performance evaluation of a green plasticizer made by enzymatic esterification of furfuryl alcohol and castor oil fatty acid.

PubMed

Mukherjee, Sohini; Ghosh, Mahua

2017-02-10

The esterification of furfuryl alcohol (FA) and castor oil fatty acid (COFA) at 3:1 molar ratio, by immobilized Candida antarctica Lipase B (NS 435 from Novozyme) in a solvent free system gave a maximum yield of 88.64% (%w/w) at 5h. Performance of the FA-COFA ester plasticized Ethyl Cellulose (EC) films were evaluated by surface morphologies, XRD analysis, mechanical properties,thermal properties, water vapor permeability and migration stability test. It was an effective plasticizer with better mechanical properties and thermal stability at the increasing concentration of FA-COFA ester (15-25%) containing EC film, than the traditional plasticizer, i.e; dibutyl phthalate (DBP) in producing good quality films. Chemical structure and the intermolecular interactions between FA-COFA ester and ethyl cellulose chains were the causative agents of these outstanding performances. Therefore, this FA-COFA ester, with significant plasticizing property, at a certain concentration, can be a substitute of DBP. Copyright © 2016 Elsevier Ltd. All rights reserved.

Ensemble characterization of an intrinsically disordered FG-Nup peptide and its F>A mutant in DMSO-d6.

PubMed

Reid, Korey M; Sunanda, Punnepalli; Raghothama, S; Krishnan, V V

2017-11-01

Intrinsically disordered proteins (IDP) lack a well-defined 3D-structure under physiological conditions, yet, the inherent disorder represented by an ensemble of conformation plays a critical role in many cellular and regulatory processes. Nucleoporins, or Nups, are the proteins found in the nuclear pore complex (NPC). The central pore of the NPC is occupied by Nups, which have phenylalanine-glycine domain repeats and are intrinsically disordered, and therefore are termed FG-Nups. These FG-domain repeats exhibit differing cohesiveness character and differ from least (FG) to most (GLFG) cohesive. The designed FG-Nup is a 25 AA model peptide containing a noncohesive FG-motif flanked by two cohesive GLFG-motifs (WT peptide). Complete NMR-based ensemble characterization of this peptide along with a control peptide with an F>A substitution (MU peptide) are discussed. Ensemble characterization of the NMR-determined models suggests that both the peptides do not have consistent secondary structures and continue to be disordered. Nonetheless, the role of cohesive elements mediated by the GLFG motifs is evident in the WT ensemble of structures that are more compact than the MU peptide. The approach presented here allows an alternate way to investigate the specific roles of distinct amino acid motifs that translate into the long-range organization of the ensemble of structures and in general on the nature of IDPs. © 2017 Wiley Periodicals, Inc.

Deprotonation of formic acid in collisions with a liquid water surface studied by molecular dynamics and metadynamics simulations.

PubMed

Murdachaew, Garold; Nathanson, Gilbert M; Benny Gerber, R; Halonen, Lauri

2016-11-21

Deprotonation of organic acids at aqueous surfaces has important implications in atmospheric chemistry and other disciplines, yet it is not well-characterized or understood. This article explores the interactions of formic acid (FA), including ionization, in collisions at the air-water interface. Ab initio molecular dynamics simulations with dispersion-corrected density functional theory were used. The 8-50 picosecond duration trajectories all resulted in the adsorption of FA within the interfacial region, with no scattering, absorption into the bulk or desorption into the vapor. Despite the known weak acidity of FA, spontaneous deprotonation of the acid was observed at the interface on a broad picosecond timescale, ranging from a few picoseconds typical for stronger acids to tens of picoseconds. Deprotonation occurred in 4% of the trajectories, and was followed by Grotthuss proton transfer through adjacent water molecules. Both sequential and ultrafast concerted proton transfer were observed. The formation of contact ion pairs and solvent-separated ion pairs, and finally the reformation of neutral FA, both trans and cis conformers, occurred in different stages of the dynamics. To better understand the deprotonation mechanisms at the interface compared with the process in bulk water, we used well-tempered metadynamics to obtain deprotonation free energy profiles. While in bulk water FA deprotonation has a free energy barrier of 14.8 kJ mol -1 , in fair agreement with the earlier work, the barrier at the interface is only 7.5 kJ mol -1 . Thus, at the air-water interface, FA may dissociate more rapidly than in the bulk. This finding can be rationalized with reference to the dissimilar aqueous solvation and hydrogen-bonding environments in the interface compared to those in bulk liquid water.

Sorption of Th (IV) to silica as a function of pH, humic/fulvic acid, ionic strength, electrolyte type.

PubMed

Chen, Changlun; Wang, Xiangke

2007-02-01

The removal behavior of thorium (Th(IV)) has been investigated in multicomponent systems containing silica (SiO2) as the model of inorganic particles because of its widespread presence in the earth's crust and soil humic acid (HA)/fulvic acid (FA) by batch experiments. The influence of pH from 2 to 12, ionic strength from 0.02 to 0.2 M KNO3, soil HA/FA concentration from 8.3 to 22.5 mg/L, and foreign cations (Li+, Na+, K+) and anions (NO3(-), Cl-) on the sorption of Th(IV) onto SiO2 was also tested. The sorption isotherms of Th(IV) at approximately constant pH (3.50+/-0.02) were determined and analyzed regressively with three kinds of sorption isotherm models, i.e., linear, Langmuir, and Freundlich models. The results demonstrated that the sorption of Th(IV) onto SiO2 increased steeply with increasing pH from 2 to 4. Generally, humic substances (HSs) were shown to enhance Th(IV) sorption at low pH, but to reduce Th(IV) sorption at intermediate and high pH. It was a hypothesis that the significantly positive influence of HA/FA at pH from 2 to 4 on the sorption of Th(IV) onto SiO2 was attributed to strong surface binding of HA/FA on SiO2 and subsequently the formation of ternary surface complexes such as [triple bond]MO-O-HA-Th or [triple bond]MO-O-FA-Th. The results also demonstrated that the sorption was strongly dependent on the concentration of HA/FA, and independent of ionic strength and foreign ions under our experimental conditions.

Effect of TiO2 addition on surface microstructure and bioactivity of fluorapatite coatings deposited using Nd:YAG laser.

PubMed

Chien, Chi-Sheng; Ko, Yu-Sheng; Kuo, Tsung-Yuan; Liao, Tze-Yuan; Lee, Tzer-Min; Hong, Ting-Fu

2014-04-01

To study the effect of titania (TiO2) addition on the surface microstructure and bioactivity of fluorapatite coatings, fluorapatite was mixed with TiO2 in 1:0.5 (FA + 0.5TiO2), 1:0.8 (FA + 0.8TiO2), and 1:1 (FA + TiO2) ratios (wt%) and clad on Ti-6Al-4V substrates using an Nd:YAG laser system. The experimental results show that the penetration depth of the weld decreases with increasing TiO2 content. Moreover, the subgrain structure of the coating layer changes from a fine cellular-like structure to a cellular-dendrite-like structure as the amount of TiO2 increases. Consequently, as the proportion of TiO2 decreases (increase in fluorapatite content), the Ca/P ratio of the coating layer also decreases. The immersion of specimens into simulated body fluid resulted in the formation of individual apatite. With a lower Ca/P ratio before immersion, the growth of the apatite was faster and then the coating layer provided a better bioactivity. X-ray diffraction analysis results show that prior to simulated body fluid immersion, the coating layer in all three specimens was composed mainly of fluorapatite, CaTiO3, and Al2O3 phases. Following simulated body fluid immersion, a peak corresponding to hydroxycarbonated apatite appeared after 2 days in the FA + 0.5TiO2 and FA + 0.8TiO2 specimens and after 7 days in the FA + TiO2 specimen. Overall, the results show that although the bioactivity of the coating layer tended to decrease with increasing TiO2 content, in accordance with the above-mentioned ratios, the bioactivity of all three specimens remained generally good.

Complementation of hypersensitivity to DNA interstrand crosslinking agents demonstrates that XRCC2 is a Fanconi anaemia gene.

PubMed

Park, Jung-Young; Virts, Elizabeth L; Jankowska, Anna; Wiek, Constanze; Othman, Mohamed; Chakraborty, Sujata C; Vance, Gail H; Alkuraya, Fowzan S; Hanenberg, Helmut; Andreassen, Paul R

2016-10-01

Fanconi anaemia (FA) is a heterogeneous inherited disorder clinically characterised by progressive bone marrow failure, congenital anomalies and a predisposition to malignancies. Determine, based on correction of cellular phenotypes, whether XRCC2 is a FA gene. Cells (900677A) from a previously identified patient with biallelic mutation of XRCC2, among other mutations, were genetically complemented with wild-type XRCC2. Wild-type XRCC2 corrects each of three phenotypes characteristic of FA cells, all related to the repair of DNA interstrand crosslinks, including increased sensitivity to mitomycin C (MMC), chromosome breakage and G2-M accumulation in the cell cycle. Further, the p.R215X mutant of XRCC2, which is harboured by the patient, is unstable. This provides an explanation for the pathogenesis of this mutant, as does the fact that 900677A cells have reduced levels of other proteins in the XRCC2-RAD51B-C-D complex. Also, FANCD2 monoubiquitination and foci formation, but not assembly of RAD51 foci, are normal in 900677A cells. Thus, XRCC2 acts late in the FA-BRCA pathway as also suggested by hypersensitivity of 900677A cells to ionising radiation. These cells also share milder sensitivities towards olaparib and formaldehyde with certain other FA cells. XRCC2/FANCU is a FA gene, as is another RAD51 paralog gene, RAD51C/FANCO. Notably, similar to a subset of FA genes that act downstream of FANCD2, biallelic mutation of XRCC2/FANCU has not been associated with bone marrow failure. Taken together, our results yield important insights into phenotypes related to FA and its genetic origins. Published by the BMJ Publishing Group Limited. For permission to use (where not already granted under a licence) please go to http://www.bmj.com/company/products-services/rights-and-licensing/

Dietary fish protein hydrolysates containing bioactive motifs affect serum and adipose tissue fatty acid compositions, serum lipids, postprandial glucose regulation and growth in obese Zucker fa/fa rats.

PubMed

Drotningsvik, Aslaug; Mjøs, Svein A; Pampanin, Daniela M; Slizyte, Rasa; Carvajal, Ana; Remman, Tore; Høgøy, Ingmar; Gudbrandsen, Oddrun A

2016-10-01

The world's fisheries and aquaculture industries produce vast amounts of protein-containing by-products that can be enzymatically hydrolysed to smaller peptides and possibly be used as additives to functional foods and nutraceuticals targeted for patients with obesity-related metabolic disorders. To investigate the effects of fish protein hydrolysates on markers of metabolic disorders, obese Zucker fa/fa rats consumed diets with 75 % of protein from casein/whey (CAS) and 25 % from herring (HER) or salmon (SAL) protein hydrolysate from rest raw material, or 100 % protein from CAS for 4 weeks. The fatty acid compositions were similar in the experimental diets, and none of them contained any long-chain n-3 PUFA. Ratios of lysine:arginine and methionine:glycine were lower in HER and SAL diets when compared with CAS, and taurine was detected only in fish protein hydrolysate diets. Motifs with reported hypocholesterolemic or antidiabetic activities were identified in both fish protein hydrolysates. Rats fed HER diet had lower serum HDL-cholesterol and LDL-cholesterol, and higher serum TAG, MUFA and n-3:n-6 PUFA ratio compared with CAS-fed rats. SAL rats gained more weight and had better postprandial glucose regulation compared with CAS rats. Serum lipids and fatty acids were only marginally affected by SAL, but adipose tissue contained less total SFA and more total n-3 PUFA when compared with CAS. To conclude, diets containing hydrolysed rest raw material from herring or salmon proteins may affect growth, lipid metabolism, postprandial glucose regulation and fatty acid composition in serum and adipose tissue in obese Zucker rats.

Self-Reported Autism Spectrum Disorder Symptoms Among Adults Referred to a Gender Identity Clinic.

PubMed

Vermaat, Lieke E W; van der Miesen, Anna I R; de Vries, Annelou L C; Steensma, Thomas D; Popma, Arne; Cohen-Kettenis, Peggy T; Kreukels, Baudewijntje P C

The purpose of this study was to (1) investigate autism spectrum disorder (ASD) symptoms in a sample of adults referred for gender dysphoria (GD) compared to typically developing (TD) populations, (2) see whether males assigned at birth with GD (MaB GD s) and females assigned at birth with GD (FaB GD s) differ in ASD symptom levels, (3) study the role of sexual orientation, and (4) investigate ASD symptoms' correlation with GD symptoms. The Autism-Spectrum Quotient (AQ) was used to measure ASD symptoms, and the Utrecht Gender Dysphoria Scale (UGDS) was used to measure the intensity of GD. Mean AQ scores of adults referred for GD (n = 326; 191 MaB GD and 135 FaB GD ) were compared to three TD populations taken from the literature (n = 1316; 667 male and 644 female, 5 birth-assigned sex unknown). The mean AQ score in individuals referred for GD was similar to the TD samples. FaB GD s showed higher mean AQ scores than MaB GD s, and they had mean scores similar to TD individuals of the same experienced gender (TD males). After selecting individuals with an UGDS score indicative of GD, a positive association between ASD and GD symptoms was found. The co-occurrence of GD and ASD in adults may not be as prevalent as previously suggested. Attenuation of sex differences in ASD might explain FaB GD s' and MaB GD s' ASD symptoms' similarity to those of TD individuals of the same experienced gender. Intensity of ASD symptoms might be correlated with intensity of GD symptoms, warranting further studies to elaborate on their potential co-occurrence.

Stimulant treatment history predicts frontal-striatal structural connectivity in adolescents with attention-deficit/hyperactivity disorder.

PubMed

Schweren, L J S; Hartman, C A; Zwiers, M P; Heslenfeld, D J; Franke, B; Oosterlaan, J; Buitelaar, J K; Hoekstra, P J

2016-04-01

Diffusion tensor imaging (DTI) has revealed white matter abnormalities in individuals with attention-deficit/hyperactivity disorder (ADHD). Stimulant treatment may affect such abnormalities. The current study investigated associations between long-term stimulant treatment and white matter integrity within the frontal-striatal and mesolimbic pathways, in a large sample of children, adolescents and young adults with ADHD. Participants with ADHD (N=172; mean age 17, range 9-26) underwent diffusion-weighted MRI scanning, along with an age- and gendermatched group of 96 control participants. Five study-specific white matter tract masks (orbitofrontal-striatal, orbitofrontal-amygdalar, amygdalar-striatal, dorsolateral-prefrontal-striatal and medialprefrontal-striatal) were created. First we analyzed case-control differences in fractional anisotropy (FA) and mean diffusivity (MD) within each tract. Second, FA and MD in each tract was predicted from cumulative stimulant intake within the ADHD group. After correction for multiple testing, participants with ADHD showed reduced FA in the orbitofrontal-striatal pathway (p=0.010, effect size=0.269). Within the ADHD group, higher cumulative stimulant intake was associated with lower MD in the same pathway (p=0.011, effect size=-0.164), but not with FA. The association between stimulant treatment and orbitofrontal-striatal MD was of modest effect size. It fell short of significance after adding ADHD severity or ADHD type to the model (p=0.036 and p=0.094, respectively), while the effect size changed little. Our findings are compatible with stimulant treatment enhancing orbitofrontal-striatal white matter connectivity, and emphasize the importance of the orbitofrontal cortex and its connections in ADHD. Longitudinal studies including a drug-naïve baseline assessment are needed to distinguish between-subject variability in ADHD severity from treatment effects. Copyright © 2016 Elsevier B.V. and ECNP. All rights reserved.

Atypical age-dependency of executive function and white matter microstructure in children and adolescents with autism spectrum disorders.

PubMed

Martínez, Kenia; Merchán-Naranjo, Jessica; Pina-Camacho, Laura; Alemán-Gómez, Yasser; Boada, Leticia; Fraguas, David; Moreno, Carmen; Arango, Celso; Janssen, Joost; Parellada, Mara

2017-11-01

Executive function (EF) performance is associated with measurements of white matter microstructure (WMS) in typical individuals. Impaired EF is a hallmark symptom of autism spectrum disorders (ASD) but it is unclear how impaired EF relates to variability in WMS. Twenty-one male youth (8-18 years) with ASD and without intellectual disability and twenty-one typical male participants (TP) matched for age, intelligence quotient, handedness, race and parental socioeconomic status were recruited. Five EF domains were assessed and several DTI-based measurements of WMS [fractional anisotropy (FA), mean diffusivity (MD) and radial diffusivity (RD)] were estimated for eighteen white matter tracts. The ASD group had lower scores for attention (F = 8.37, p = 0.006) and response inhibition (F = 13.09, p = 0.001). Age-dependent changes of EF performance and WMS measurements were present in TP but attenuated in the ASD group. The strongest diagnosis-by-age effect was found for forceps minor, left anterior thalamic radiation and left cingulum angular bundle (all p's ≤ 0.002). In these tracts subjects with ASD tended to have equal or increased FA and/or reduced MD and/or RD at younger ages while controls had increased FA and/or reduced MD and/or RD thereafter. Only for TP individuals, increased FA in the left anterior thalamic radiation was associated with better response inhibition, while reduced RD in forceps minor and left cingulum angular bundle was related to better problem solving and working memory performance respectively. These findings provide novel insight into the age-dependency of EF performance and WMS in ASD, which can be instructive to cognitive training programs.

Synthesis and characterization of zeolite from coal fly ash

NASA Astrophysics Data System (ADS)

Liu, Yong; Luo, Qiong; Wang, Guodong; Li, Xianlong; Na, Ping

2018-05-01

Fly ash (FA) from coal-based thermal power plant was used to synthesize zeolite in NaOH solution with hydrothermal method in this work. Firstly, the effects of calcination and acid treatment on the removal of impurities in fly ash were studied. Then based on the pretreated FA, the effects of alkali concentration, reaction temperature and Si/Al ratio on the synthesis of zeolite were studied in detail. The mineralogy, morphology, thermal behavior, infrared spectrum and specific surface for the synthetic sample were investigated. The results indicated that calcination at 750 °C for 1.5 h can basically remove unburned carbon from FA, and 4 M hydrochloric acid treatment of calcined FA at 90 °C for 2 h will reduce the quality of about 34.3%wt, which are mainly iron, calcium and sulfur elements. The concentration of NaOH, reaction temperature and Si/Al ratio have important effect on the synthesis of zeolite. In this study, 0.5 M NaOH cannot obtain any zeolite. High temperature is beneficial to zeolite synthesis from FA, but easily lead to a variety of zeolites. The synthetic sample contains three kinds of zeolites such as zeolite P, sodalite and zeolite X, when the reaction conditions are 2 M NaOH and 120 °C for 24 h. In this research, quartz always exists in the synthetic sample, but will reduce with the increase of temperature. The synthetic zeolite has the specific surface area of about 42 m2 g‑1 and better thermal stability.

Toxicity of cosmetic preservatives on human ocular surface and adnexal cells.

PubMed

Chen, Xiaomin; Sullivan, David A; Sullivan, Amy Gallant; Kam, Wendy R; Liu, Yang

2018-05-01

Cosmetic products, such as mascara, eye shadow, eyeliner and eye makeup remover are used extensively to highlight the eyes or clean the eyelids, and typically contain preservatives to prevent microbial growth. These preservatives include benzalkonium chloride (BAK) and formaldehyde (FA)-releasing preservatives. We hypothesize that these preservatives, at concentrations (BAK = 1 mg/ml; FA = 0.74 mg/ml) approved for consumer use, are toxic to human ocular surface and adnexal cells. Accordingly, we tested the influence of BAK and FA on the morphology, survival, and proliferation and signaling ability of immortalized human meibomian gland (iHMGECs), corneal (iHCECs) and conjunctival (iHConjECs) epithelial cells. iHMGECs, iHCECs and iHConjECs were cultured with different concentrations of BAK (5 μg/ml to 0.005 μg/ml) or FA (1 mg/ml to 1 μg/ml) under basal, proliferating or differentiating conditions up to 7 days. We used low BAK levels, because we found that 0.5 mg/ml and 50 μg/ml BAK killed iHMGECs within 1 day after a 15 min exposure. Experimental procedures included analyses of cell appearance, cell number, and neutral lipid content (LipidTox), lysosome accumulation (LysoTracker) and AKT signaling in all 3 cell types. Our results demonstrate that BAK and FA cause dose-dependent changes in the morphology, survival, proliferation and AKT signaling of iHMGECs, iHCECs and iHConjECs. Many of the concentrations tested induced cell atrophy, poor adherence, decreased proliferation and death, after 5 days of exposure. Cellular signaling, as indicated by AKT phosphorylation after 15 (FA) or 30 (BAK) minutes of treatment, was also reduced in a dose-dependent fashion in all 3 cell types, irrespective of whether cells had been cultured under proliferating or differentiating conditions. Our results support our hypothesis and demonstrate that the cosmetic preservatives, BAK and FA, exert many toxic effects on cells of the ocular surface and adnexa. Copyright © 2018 Elsevier Ltd. All rights reserved.

Contribution of the hydrostatic pressure to the shape of silver island particles

NASA Astrophysics Data System (ADS)

Anno, E.; Hoshino, R.

1984-09-01

We have investigated the shape change of silver island particles caused by the surface energy reduction. When the surface energy was reduced by the reaction with hydrogen sulfide, the flattening of the particles was observed. As is well known, the similar shape change takes place when the particle size increases. Therefore, the particle shape is considered to depend both on the surface energy and the particle size. From this consideration, we predict the contribution of the hydrostatic pressure P to the particle shape. As evidence of this contribution, we consider the existence of the critical size below which P is larger than the adhesive force FA between deposit and substrate surface. Investigating the influence of the flattening due to the surface energy reduction on the size distribution, the critical size is found and estimated to be about 80 Å in diameter. This value is comparable with that estimated from the condition P = FA.

Impact of innate immunity in a subset of children with autism spectrum disorders: a case control study.

PubMed

Jyonouchi, Harumi; Geng, Lee; Cushing-Ruby, Agnes; Quraishi, Huma

2008-11-21

Among patients with autism spectrum disorders (ASD) evaluated in our clinic, there appears to be a subset that can be clinically distinguished from other ASD children because of frequent infections (usually viral) accompanied by worsening behavioural symptoms and/or loss/decrease in acquired skills. This study assessed whether these clinical features of this ASD subset are associated with atopy, asthma, food allergy (FA), primary immunodeficiency (PID), or innate immune responses important in viral infections. This study included the ASD children described above (ASD test, N = 26) and the following controls: ASD controls (N = 107), non-ASD controls with FA (N = 24), non-ASD controls with chronic rhinosinusitis/recurrent otitis media (CRS/ROM; N = 38), and normal controls (N = 43). We assessed prevalence of atopy, asthma, FA, CRS/ROM, and PID. Innate immune responses were assessed by measuring production of proinflammatory and counter-regulatory cytokines by peripheral blood mononuclear cells (PBMCs) in response to agonists of Toll-like receptors (TLRs), with or without pre-treatment of lipopolysaccharide (LPS), a TLR4 agonist. Non-IgE mediated FA was equally prevalent in both ASD test and ASD control groups, occurring at higher frequency than in the non-ASD controls. Allergic rhinitis, atopic/non-atopic asthma, and atopic dermatitis were equally prevalent among the study groups except for the CRS/ROM group in which non-atopic asthma was more prevalent (52.6%). CRS/ROM and specific polysaccharide antibody deficiency (SPAD) were more prevalent in the ASD test group than in the ASD control, FA, and normal control groups: 23.1% vs. < 5% for CRS/ROS and 19.2% vs. < 1% for SPAD. However, CRS/ROM patients had the highest prevalence of SPAD (34.2%). When compared to ASD and normal case controls, PBMCs from 19 non-SPAD, ASD test group children produced: 1) less IL-1beta with a TLR7/8 agonist, less IL-10 with a TLR2/6 agonist, and more IL-23 with a TLR4 agonist without LPS pre-treatment, and 2) less IL-1beta with TLR4/7/8 agonists with LPS pre-treatment. These are cytokines associated with the neuro-immune network. Clinical features of the ASD test group were not associated with atopy, asthma, FA, or PID in our study but may be associated with altered TLR responses mediating neuro-immune interactions.

White Matter Integrity and Treatment-Based Change in Speech Performance in Minimally Verbal Children with Autism Spectrum Disorder.

PubMed

Chenausky, Karen; Kernbach, Julius; Norton, Andrea; Schlaug, Gottfried

2017-01-01

We investigated the relationship between imaging variables for two language/speech-motor tracts and speech fluency variables in 10 minimally verbal (MV) children with autism. Specifically, we tested whether measures of white matter integrity-fractional anisotropy (FA) of the arcuate fasciculus (AF) and frontal aslant tract (FAT)-were related to change in percent syllable-initial consonants correct, percent items responded to, and percent syllable insertion errors (from best baseline to post 25 treatment sessions). Twenty-three MV children with autism spectrum disorder (ASD) received Auditory-Motor Mapping Training (AMMT), an intonation-based treatment to improve fluency in spoken output, and we report on seven who received a matched control treatment. Ten of the AMMT participants were able to undergo a magnetic resonance imaging study at baseline; their performance on baseline speech production measures is compared to that of the other two groups. No baseline differences were found between groups. A canonical correlation analysis (CCA) relating FA values for left- and right-hemisphere AF and FAT to speech production measures showed that FA of the left AF and right FAT were the largest contributors to the synthetic independent imaging-related variable. Change in percent syllable-initial consonants correct and percent syllable-insertion errors were the largest contributors to the synthetic dependent fluency-related variable. Regression analyses showed that FA values in left AF significantly predicted change in percent syllable-initial consonants correct, no FA variables significantly predicted change in percent items responded to, and FA of right FAT significantly predicted change in percent syllable-insertion errors. Results are consistent with previously identified roles for the AF in mediating bidirectional mapping between articulation and acoustics, and the FAT in its relationship to speech initiation and fluency. They further suggest a division of labor between the hemispheres, implicating the left hemisphere in accuracy of speech production and the right hemisphere in fluency in this population. Changes in response rate are interpreted as stemming from factors other than the integrity of these two fiber tracts. This study is the first to document the existence of a subgroup of MV children who experience increases in syllable- insertion errors as their speech develops in response to therapy.

Self-assembly and reactive molding techniques for controlling the interface and dispersion of the particulate phase in nanocomposites

NASA Astrophysics Data System (ADS)

Pranger, Lawrence A.

This research explored the processing and properties of PNCs using a polyfurfural alcohol (PFA) matrix. The precursor for PFA, furfuryl alcohol (FA) is sourced from feedstocks rich in hemicellulose, such as corn cobs, oat hulls and wood. To exploit FA as a polymerizable solvent, cellulose whiskers (CW) and montmorillonite clay (MMT) were used as the nanoparticle phase. Results from PNC processing show that CW and MMT can be dispersed in the PFA matrix by means of insitu polymerization, without the use of surfactants or dilution in solvents. Both CW and MMT nanoparticles catalyze the polymerization of furfuryl alcohol (FA). Moreover, the insitu intercalative polymerization of FA in the interlayer galleries of MMT leads to the complete exfoliation of the MMT in the PFA matrix. CW and MMT both function as effective matrix modifiers, increasing the thermal stability of PFA nanocomposites compared to pure PFA polymer. The increased thermal stability is seen as significant increases in the onset of degradation and in residual weight at high temperature. This research also explored the surface functionalization of Cu, Ni and Pt substrates by self-assembly of a range of difunctional linker molecules. Characterization by XPS and PM-IRRAS indicate that diisocyanides and dicarboxylic acids both form chemically "sticky" surfaces after self-assembly on Cu and Ni. Sticky surfaces may provide a means of increasing nanoparticle dispersion in metal nanocluster filled PNCs, by increasing their interaction with the matrix polymer. Another potential application for sticky surfaces on Cu is in the ongoing miniaturization of circuit boards. The functionalization of Cu bond pad substrates with linker molecules may provide an alternate means of bonding components to their bond pads, with higher placement accuracy compared to solder bumps.

Spectrum of sequence variations in the FANCA gene: an International Fanconi Anemia Registry (IFAR) study.

PubMed

Levran, Orna; Diotti, Raffaella; Pujara, Kanan; Batish, Sat D; Hanenberg, Helmut; Auerbach, Arleen D

2005-02-01

Fanconi anemia (FA) is an autosomal recessive disorder that is defined by cellular hypersensitivity to DNA cross-linking agents, and is characterized clinically by developmental abnormalities, progressive bone-marrow failure, and predisposition to leukemia and solid tumors. There is extensive genetic heterogeneity, with at least 11 different FA complementation groups. FA-A is the most common group, accounting for approximately 65% of all affected individuals. The mutation spectrum of the FANCA gene, located on chromosome 16q24.3, is highly heterogeneous. Here we summarize all sequence variations (mutations and polymorphisms) in FANCA described in the literature and listed in the Fanconi Anemia Mutation Database as of March 2004, and report 61 novel FANCA mutations identified in FA patients registered in the International Fanconi Anemia Registry (IFAR). Thirty-eight novel SNPs, previously unreported in the literature or in dbSNP, were also identified. We studied the segregation of common FANCA SNPs in FA families to generate haplotypes. We found that FANCA SNP data are highly useful for carrier testing, prenatal diagnosis, and preimplantation genetic diagnosis, particularly when the disease-causing mutations are unknown. Twenty-two large genomic deletions were identified by detection of apparent homozygosity for rare SNPs. In addition, a conserved SNP haplotype block spanning at least 60 kb of the FANCA gene was identified in individuals from various ethnic groups. (c) 2005 Wiley-Liss, Inc.

Microstructural effects of Ramadan fasting on the brain: a diffusion tensor imaging study.

PubMed

Bakan, Ayse Ahsen; Yıldız, Seyma; Alkan, Alpay; Yetis, Huseyin; Kurtcan, Serpil; Ilhan, Mahmut Muzaffer

2015-01-01

We aimed to examine whether the brain displays any microstructural changes after a three-week Ramadan fasting period using diffusion tenson imaging. This study included a study and a control group of 25 volunteers each. In the study group, we examined and compared apparent diffusion coefficient (ADC) and fractional anisotropy (FA) values of the participants during (phase 1) and after (phase 2) a period of fasting. The control group included individuals who did not fast. ADC and FA values obtained in phase 1 and phase 2 were compared between the study and control groups. In the study group, ADC values of hypothalamus and, to a lesser extent, of insula were lower in phase 1 compared with phase 2 and the control group. The FA values of amygdala, middle temporal cortex, thalamus and, to a lesser extent, of medial prefrontal cortex were lower in phase 1 compared with phase 2 and the control group. Phase 2 ADC and FA values of the study group were not significantly different compared with the control group at any brain location. A three-week Ramadan fasting period can cause microstructural changes in the brain, and diffusion tensor imaging enables the visualization of these changes. The identification of brain locations where changes occurred in ADC and FA values during fasting can be helpful in diagnostic imaging and understanding the pathophysiology of eating disorders.

Tract-based spatial statistics analysis of white matter changes in children with anisometropic amblyopia.

PubMed

Li, Qian; Zhai, Liying; Jiang, Qinying; Qin, Wen; Li, Qingji; Yin, Xiaohui; Guo, Mingxia

2015-06-15

Amblyopia is a neurological disorder of vision that follows abnormal binocular interaction or visual deprivation during early life. Previous studies have reported multiple functional or structural cortical alterations. Although white matter was also studied, it still cannot be clarified clearly which fasciculus was affected by amblyopia. In the present study, tract-based spatial statistics analysis was applied to diffusion tensor imaging (DTI) to investigate potential diffusion changes of neural tracts in anisometropic amblyopia. Fractional anisotropy (FA) value was calculated and compared between 20 amblyopic children and 18 healthy age-matched controls. In contrast to the controls, significant decreases in FA values were found in right optic radiation (OR), left inferior longitudinal fasciculus/inferior fronto-occipital fasciculus (ILF/IFO) and right superior longitudinal fasciculus (SLF) in the amblyopia. Furthermore, FA values of these identified tracts showed positive correlation with visual acuity. It can be inferred that abnormal visual input not only hinders OR from well developed, but also impairs fasciculi associated with dorsal and ventral visual pathways, which may be responsible for the amblyopic deficiency in object discrimination and stereopsis. Increased FA was detected in right posterior part of corpus callosum (CC) with a medium effect size, which may be due to compensation effect. DTI with subsequent measurement of FA is a useful tool for investigating neuronal tract involvement in amblyopia. Copyright © 2015 Elsevier Ireland Ltd. All rights reserved.

Endocrinopathies, Bone Health, and Insulin Resistance in Patients with Fanconi Anemia after Hematopoietic Cell Transplantation

PubMed Central

Barnum, Jessie L.; Petryk, Anna; Zhang, Lei; DeFor, Todd E.; Baker, K. Scott; Steinberger, Julia; Nathan, Brandon; Wagner, John E.; MacMillan, Margaret L.

2017-01-01

A number of endocrinopathies have been described after hematopoietic cell transplantation (HCT), but data are limited in patients with Fanconi anemia (FA). We report several endocrine-based disorders in a cohort of 44 patients with FA after HCT compared with both 74 patients who received HCT for hematologic malignancies and with 275 healthy controls. Endocrinopathies assessed included hypothyroidism, hypogonadism, short stature, dyslipidemia, insulin resistance, abnormalities in body composition, and bone health. Most (86%) patients with FA had at least 1 endocrinopathy, with 11% having 3 or more. Hypothyroidism was seen in 57%, hypogonadism in 27%, short stature in 50%, and reduced total body and lumbar spine bone mineral density (BMD) (height adjusted Z-score < −1) in 57% and 21%, respectively. Vitamin D deficiency was seen in 71%. Short stature was associated with younger age at HCT and gonadal failure was associated with older age at HCT. Insulin resistance was associated with increased percent fat mass and increased android/gynoid ratio by dual energy X-ray absorptiometry. Hypothyroidism, short stature, and reduced total body BMD were more prevalent in patients with FA compared with patients with hematologic malignancies. We recommend an assessment before transplantation and close follow-up afterwards to ensure proper clinical management. Future studies should continue to explore the impact of HCT on endocrinopathies in FA patients. PMID:27180116

Microstructural effects of Ramadan fasting on the brain: a diffusion tensor imaging study

PubMed Central

Bakan, Ayse Ahsen; Yıldız, Seyma; Alkan, Alpay; Yetis, Huseyin; Kurtcan, Serpil; Ilhan, Mahmut Muzaffer

2015-01-01

PURPOSE We aimed to examine whether the brain displays any microstructural changes after a three-week Ramadan fasting period using diffusion tenson imaging. METHODS This study included a study and a control group of 25 volunteers each. In the study group, we examined and compared apparent diffusion coefficient (ADC) and fractional anisotropy (FA) values of the participants during (phase 1) and after (phase 2) a period of fasting. The control group included individuals who did not fast. ADC and FA values obtained in phase 1 and phase 2 were compared between the study and control groups. RESULTS In the study group, ADC values of hypothalamus and, to a lesser extent, of insula were lower in phase 1 compared with phase 2 and the control group. The FA values of amygdala, middle temporal cortex, thalamus and, to a lesser extent, of medial prefrontal cortex were lower in phase 1 compared with phase 2 and the control group. Phase 2 ADC and FA values of the study group were not significantly different compared with the control group at any brain location. CONCLUSION A three-week Ramadan fasting period can cause microstructural changes in the brain, and diffusion tensor imaging enables the visualization of these changes. The identification of brain locations where changes occurred in ADC and FA values during fasting can be helpful in diagnostic imaging and understanding the pathophysiology of eating disorders. PMID:25835077

BIK (NBK) is a mediator of the sensitivity of Fanconi anaemia group C lymphoblastoid cell lines to interstrand DNA cross-linking agents.

PubMed

Prieto-Remón, Inés; Sánchez-Carrera, Dámaso; López-Duarte, Mónica; Richard, Carlos; Pipaón, Carlos

2012-11-15

FA (Fanconi anaemia) is a rare hereditary disorder characterized by congenital malformations, progressive bone marrow failure and an extraordinary predisposition to develop cancer. At present, 15 genes have been related to this condition and mutations of them have also been found in different types of cancer. Bone marrow failure threatens the life of FA patients during the first decade of their life, but the mechanisms underlying this process are not completely understood. In the present study we investigate a possible imbalance between the expression of pro- and anti-apoptotic proteins as a cause for the hypersensitivity of FANCC (FA, complementation group C)-deficient cells to genotoxic stress. We found a BIK (Bcl-2 interacting killer) over-expression in lymphoblastoid cell lines derived from FA-C patients when compared with their phenotypically corrected counterparts. This overexpression has a transcriptional basis since the regulatory region of the gene shows higher activity in FANCC-deficient cells. We demonstrate the involvement of BIK in the sensitivity of FA-C lymphoblasts to interstrand DNA cross-linking agents as it is induced by these drugs and interference of its expression in these cells preserves their viability and reduces apoptosis. We investigate the mechanism of BIK overexpression in FANCC-deficient cells by analysing the activity of many different signalling pathways in these cells. Finally, we provide evidence of a previously undescribed indirect epigenetic regulation of BIK in FA-C lymphoblasts mediated by ΔNp73, an isoform of p73 lacking its transactivation domain that activates BIK through a proximal element in its promoter.

Mitochondrial respiratory chain Complex I defects in Fanconi anemia complementation group A.

PubMed

Ravera, Silvia; Vaccaro, Daniele; Cuccarolo, Paola; Columbaro, Marta; Capanni, Cristina; Bartolucci, Martina; Panfoli, Isabella; Morelli, Alessandro; Dufour, Carlo; Cappelli, Enrico; Degan, Paolo

2013-10-01

Fanconi anemia (FA) is a rare and complex inherited blood disorder of the child. At least 15 genes are associated with the disease. The highest frequency of mutations belongs to groups A, C and G. Genetic instability and cytokine hypersensitivity support the selection of leukemic over non-leukemic stem cells. FA cellular phenotype is characterized by alterations in red-ox state, mitochondrial functionality and energy metabolism as reported in the past however a clear picture of the altered biochemical phenotype in FA is still elusive and the final biochemical defect(s) still unknown. Here we report an analysis of the respiratory fluxes in FANCA primary fibroblasts, lymphocytes and lymphoblasts. FANCA mutants show defective respiration through Complex I, diminished ATP production and metabolic sufferance with an increased AMP/ATP ratio. Respiration in FANCC mutants is normal. Treatment with N-acetyl-cysteine (NAC) restores oxygen consumption to normal level. Defective respiration in FANCA mutants appear correlated with the FA pro-oxidative phenotype which is consistent with the altered morphology of FANCA mitochondria. Electron microscopy measures indeed show profound alterations in mitochondrial ultrastructure and shape. Copyright © 2013 Elsevier Masson SAS. All rights reserved.

Spectrum of FANCA mutations in Italian Fanconi anemia patients: identification of six novel alleles and phenotypic characterization of the S858R variant.

PubMed

Savino, Maria; Borriello, Adriana; D'Apolito, Maria; Criscuolo, Maria; Del Vecchio, Maria; Bianco, Anna Monica; Di Perna, Michele; Calzone, Rita; Nobili, Bruno; Zatterale, Adriana; Zelante, Leopoldo; Joenje, Hans; Della Ragione, Fulvio; Savoia, Anna

2003-10-01

Fanconi anemia (FA) is an autosomal recessive disorder characterized by genomic instability, bone marrow failure, congenital malformations, and cancer predisposition. FA is a genetically heterogeneous disease with at least seven genes so far identified. The role of FA proteins is unknown although they interact in a common functional pathway. Here, we report six novel FANCA sequence changes and review all the mutations identified in Italy. Except for two missense substitutions, all are expected to cause a premature termination of the FANCA protein at various sites throughout the molecule. The premature terminations are due to nonsense and splice site mutations, as well as small insertions and deletions, and large genomic rearrangements. The expected truncated proteins were not detectable on Western blot analyses. The FANCA-S858R variant is instead expressed at lower level than that seen in normal cell lines and is associated with a non-ubiquinated FANCD2 protein, strongly suggesting that the amino acid substitution is a disease-causing mutation. The spectrum of FA mutations is widely in agreement with the heterogeneous ethnic origin of the Italian population. Copyright 2003 Wiley-Liss, Inc.

Impaired Frontal-Limbic White Matter Maturation in Children at Risk for Major Depression.

PubMed

Hung, Yuwen; Saygin, Zeynep M; Biederman, Joseph; Hirshfeld-Becker, Dina; Uchida, Mai; Doehrmann, Oliver; Han, Michelle; Chai, Xiaoqian J; Kenworthy, Tara; Yarmak, Pavel; Gaillard, Schuyler L; Whitfield-Gabrieli, Susan; Gabrieli, John D E

2017-09-01

Depression is among the most common neuropsychiatric disorders. It remains unclear whether brain abnormalities associated with depression reflect the pathological state of the disease or neurobiological traits predisposing individuals to depression. Parental history of depression is a risk factor that more than triples the risk of depression. We compared white matter (WM) microstructure cross-sectionally in 40 children ages 8-14 with versus without parental history of depression (At-Risk vs. Control). There were significant differences in age-related changes of fractional anisotropy (FA) between the groups, localized in the anterior fronto-limbic WM pathways, including the anterior cingulum and the genu of the corpus callosum. Control children exhibited typical increasing FA with age, whereas At-Risk children exhibited atypical decreasing FA with age in these fronto-limbic regions. Furthermore, dorsal cingulate FA significantly correlated with depressive symptoms for At-Risk children. The results suggest maturational WM microstructure differences in mood-regulatory neurocircuitry that may contribute to neurodevelopmental risk for depression. The study provides new insights into neurodevelopmental susceptibility to depression and related disabilities that may promote early preventive intervention approaches. © The Author 2016. Published by Oxford University Press. All rights reserved. For Permissions, please e-mail: journals.permissions@oup.com.

FA(I):A(+) and FA(II):Cu(+) laser activity and photographic sensitization at the low coordinated surfaces of AgBr ab initio calculations.

PubMed

Shalabi, A S

2002-08-01

The twofold potentials of F(A)(I):Au(+) and F(A)(II)Cu(+) color centers at the low coordinated surfaces of AgBr thin films in providing tunable laser activity and photographic sensitization were investigated using ab initio methods of molecular electronic structure calculations. Clusters of variable size were embedded in simulated Coulomb fields that closely approximated the Madelung fields of the host surfaces, and the nearest neighbor ions to the F(A) defect site were allowed to relax to equilibrium in each case. Based on the calculated Stokes shifted optical transition bands and horizontal shifts along the configuration coordinate diagrams, both F(A)(I):Au(+) and F(A)(II):Cu(+) color centers were found to be laser active. The laser activity faded quickly as the bromide ion coordination decreased from 5 (flat) to 4 (edge) to 3 (corner) and as the size of the impurity cation increased from Cu(+) to Au(+). The latter relation was explainable in terms of the axial perturbation of the impurity cation. The smallest calculated Stokes-shift at the corner surface suggested that emission had the same oscillator strength as absorption. All relaxed excited states RESs of the defect containing surfaces were deep below the lower edges of the conduction bands of the defect free ground state surfaces, indicating that F(A)(I):Au(+) and F(A)(II):Cu(+) are suitable laser defects. The probability of orientational destruction of the two centers attributed to the assumed RES saddle point ion configurations along the <110> axis was found to be directly proportional to the size of the impurity cation, with activation energy barriers of about 0.655-3.294 eV for Cu(+), and about 1.887-3.404 eV for Au(+). The possibility of exciton (energy) transfer from the sites of higher coordination to those of lower coordination is demonstrated. The more laser active F(A)(II):Cu(+) center was more easily formed than the less laser active F(A)(I):Au(+) center. The Glasner-Tompkins empirical relation was generalized to include F(A) centers at the low coordinated surfaces of silver bromide thin film. As far as color photographic sensitization is concerned, the lowest unoccupied molecular orbitals of the selected dye molecules in the excited states were high enough for electron injection. F(A) defect formation and rotational diffusion of silver clusters reduced the energy gaps between the excited dye molecules and the lower edges of the conduction bands and allowed for hole injection. About 54-60% of the reduction of silver ions at the flat surface of AgBr was attributed to the host anions and F(A) defect formation, leaving about 40-46% for the reduction of photoelectrons as well as the electrons of the developer or dye molecules. The unrelaxed rotational diffusions of the central Ag(4) by 90 degrees decreased the latter percentage, but were severely hindered by activation energy barriers. Copyright 2002 Wiley Periodicals, Inc. J Comput Chem 23: 1104-1120, 2002

White matter microstructural abnormalities in girls with chromosome 22q11.2 deletion syndrome, Fragile X or Turner syndrome as evidenced by diffusion tensor imaging

PubMed Central

Villalon, Julio; Jahanshad, Neda; Beaton, Elliott; Toga, Arthur W.; Thompson, Paul M.; Simon, Tony J.

2014-01-01

Children with chromosome 22q11.2 Deletion Syndrome (22q11.2DS), Fragile X Syndrome (FXS), or Turner Syndrome (TS) are considered to belong to distinct genetic groups, as each disorder is caused by separate genetic alterations. Even so, they have similar cognitive and behavioral dysfunctions, particularly in visuospatial and numerical abilities. To assess evidence for common underlying neural microstructural alterations, we set out to determine whether these groups have partially overlapping white matter abnormalities, relative to typically developing controls. We scanned 101 female children between 7 and 14 years old: 25 with 22q11.2DS, 18 with FXS, 17 with TS, and 41 aged-matched controls using diffusion tensor imaging (DTI). Anisotropy and diffusivity measures were calculated and all brain scans were nonlinearly aligned to population and site-specific templates. We performed voxel-based statistical comparisons of the DTI-derived metrics between each disease group and the controls, while adjusting for age. Girls with 22q11.2DS showed lower fractional anisotropy (FA) than controls in the association fibers of the superior and inferior longitudinal fasciculi, the splenium of the corpus callosum, and the corticospinal tract. FA was abnormally lower in girls with FXS in the posterior limbs of the internal capsule, posterior thalami, and precentral gyrus. Girls with TS had lower FA in the inferior longitudinal fasciculus, right internal capsule and left cerebellar peduncle. Partially overlapping neurodevelopmental anomalies were detected in all three neurogenetic disorders. Altered white matter integrity in the superior and inferior longitudinal fasciculi and thalamic to frontal tracts may contribute to the behavioral characteristics of all of these disorders. PMID:23602925

Microstructural White Matter Alterations in the Corpus Callosum of Girls With Conduct Disorder.

PubMed

Menks, Willeke Martine; Furger, Reto; Lenz, Claudia; Fehlbaum, Lynn Valérie; Stadler, Christina; Raschle, Nora Maria

2017-03-01

Diffusion tensor imaging (DTI) studies in adolescent conduct disorder (CD) have demonstrated white matter alterations of tracts connecting functionally distinct fronto-limbic regions, but only in boys or mixed-gender samples. So far, no study has investigated white matter integrity in girls with CD on a whole-brain level. Therefore, our aim was to investigate white matter alterations in adolescent girls with CD. We collected high-resolution DTI data from 24 girls with CD and 20 typically developing control girls using a 3T magnetic resonance imaging system. Fractional anisotropy (FA) and mean diffusivity (MD) were analyzed for whole-brain as well as a priori-defined regions of interest, while controlling for age and intelligence, using a voxel-based analysis and an age-appropriate customized template. Whole-brain findings revealed white matter alterations (i.e., increased FA) in girls with CD bilaterally within the body of the corpus callosum, expanding toward the right cingulum and left corona radiata. The FA and MD results in a priori-defined regions of interest were more widespread and included changes in the cingulum, corona radiata, fornix, and uncinate fasciculus. These results were not driven by age, intelligence, or attention-deficit/hyperactivity disorder comorbidity. This report provides the first evidence of white matter alterations in female adolescents with CD as indicated through white matter reductions in callosal tracts. This finding enhances current knowledge about the neuropathological basis of female CD. An increased understanding of gender-specific neuronal characteristics in CD may influence diagnosis, early detection, and successful intervention strategies. Copyright © 2017 American Academy of Child and Adolescent Psychiatry. Published by Elsevier Inc. All rights reserved.

Impaired anatomical connectivity and related executive functions: differentiating vulnerability and disease marker in bipolar disorder.

PubMed

Linke, Julia; King, Andrea V; Poupon, Cyril; Hennerici, Michael G; Gass, Achim; Wessa, Michèle

2013-12-15

Bipolar 1 disorder (BD1) has been associated with impaired set shifting, increased risk taking, and impaired integrity of frontolimbic white matter. However, it remains unknown to what extent these findings are related to each other and whether these abnormalities represent risk factors or consequences of the illness. We addressed the first question by comparing 19 patients with BD1 and 19 healthy control subjects (sample 1) with diffusion tensor imaging, the Intra-Extra Dimensional Set Shift Task, and the Cambridge Gambling Task. The second question we approached by applying the same protocol to 22 healthy first-degree relatives of patients with BD1 and 22 persons without a family history of mental disorders (sample 2). In comparison with their control groups, BD1 patients and healthy first-degree relatives of patients with BD1 showed significantly reduced fractional anisotropy (FA) in the right anterior limb of the internal capsule and right uncinate fasciculus. White matter integrity in corpus callosum was reduced in BD1 patients only. In addition, reduced FA in anterior limb of the internal capsule correlated significantly with an increased number of errors during set shifting and increased risk taking and reduced FA in uncinate fasciculus correlated significantly with increased risk taking. Similar white matter alterations in BD1 patients and healthy relatives of BD1 patients are associated with comparable behavioral abnormalities. Further, results indicate that altered frontolimbic and frontothalamic connectivity and corresponding behavioral abnormalities might be a trait and vulnerability marker of BD1, whereas interhemispheric connectivity appears to be a disease marker. Copyright © 2013 Society of Biological Psychiatry. Published by Elsevier Inc. All rights reserved.

Distortion-free diffusion tensor imaging for evaluation of lumbar nerve roots: Utility of direct coronal single-shot turbo spin-echo diffusion sequence.

PubMed

Sakai, Takayuki; Doi, Kunio; Yoneyama, Masami; Watanabe, Atsuya; Miyati, Tosiaki; Yanagawa, Noriyuki

2018-06-01

Diffusion tensor imaging (DTI) based on a single-shot echo planer imaging (EPI-DTI) is an established method that has been used for evaluation of lumbar nerve disorders in previous studies, but EPI-DTI has problems such as a long acquisition time, due to a lot of axial slices, and geometric distortion. To solve these problems, we attempted to apply DTI based on a single-shot turbo spin echo (TSE-DTI) with direct coronal acquisition. Our purpose in this study was to investigate whether TSE-DTI may be more useful for evaluation of lumbar nerve disorders than EPI-DTI. First, lumbar nerve roots of five healthy volunteers were evaluated for optimization of imaging parameters with TSE-DTI including b-values and the number of motion proving gradient (MPG) directions. Subsequently, optimized TSE-DTI was quantitatively compared with conventional EPI-DTI by using fractional anisotropy (FA) values and visual scores in subjective visual evaluation of tractography. Lumbar nerve roots of six patients, who had unilateral neurologic symptoms in one leg, were evaluated by the optimized TSE-DTI. TSE-DTI with b-value of 400 s/mm 2 and 32 diffusion-directions could reduce the image distortion compared with EPI-DTI, and showed that the average FA values on the symptomatic side for six patients were significantly lower than those on the non-symptomatic side (P < 0.05). Tractography with TSE-DTI might show damaged areas of lumbar nerve roots without severe image distortion. TSE-DTI might improve the reproducibility in measurements of FA values for quantification of a nerve disorder, and would become a useful tool for diagnosis of low back pain. Copyright © 2018 Elsevier Inc. All rights reserved.

Dissolved Organic Matter Quality in a Shallow Aquifer of Bangladesh: Implications for Arsenic Mobility.

PubMed

Mladenov, Natalie; Zheng, Yan; Simone, Bailey; Bilinski, Theresa M; McKnight, Diane M; Nemergut, Diana; Radloff, Kathleen A; Rahman, M Moshiur; Ahmed, Kazi Matin

2015-09-15

In some high arsenic (As) groundwater systems, correlations are observed between dissolved organic matter (DOM) and As concentrations, but in other systems, such relationships are absent. The role of labile DOM as the main driver of microbial reductive dissolution is not sufficient to explain the variation in DOM-As relationships. Other processes that may also influence As mobility include complexation of As by dissolved humic substances, and competitive sorption and electron shuttling reactions mediated by humics. To evaluate such humic DOM influences, we characterized the optical properties of filtered surface water (n = 10) and groundwater (n = 24) samples spanning an age gradient in Araihazar, Bangladesh. Further, we analyzed large volume fulvic acid (FA) isolates (n = 6) for optical properties, C and N content, and (13)C NMR spectroscopic distribution. Old groundwater (>30 years old) contained primarily sediment-derived DOM and had significantly higher (p < 0.001) dissolved As concentration than groundwater that was younger than 5 years old. Younger groundwater had DOM spectroscopic signatures similar to surface water DOM and characteristic of a sewage pollution influence. Associations between dissolved As, iron (Fe), and FA concentration and fluorescence properties of isolated FA in this field study suggest that aromatic, terrestrially derived FAs promote As-Fe-FA complexation reactions that may enhance As mobility.

Development and Characterization of a High Sensitivity Segmented Fast Neutron Spectrometer (FaNS-2)

PubMed Central

Langford, T.J.; Beise, E.J.; Breuer, H.; Heimbach, C.R.; Ji, G.; Nico, J.S.

2016-01-01

We present the development of a segmented fast neutron spectrometer (FaNS-2) based upon plastic scintillator and 3He proportional counters. It was designed to measure both the flux and spectrum of fast neutrons in the energy range of few MeV to 1 GeV. FaNS-2 utilizes capture-gated spectroscopy to identify neutron events and reject backgrounds. Neutrons deposit energy in the plastic scintillator before capturing on a 3He nucleus in the proportional counters. Segmentation improves neutron energy reconstruction while the large volume of scintillator increases sensitivity to low neutron fluxes. A main goal of its design is to study comparatively low neutron fluxes, such as cosmogenic neutrons at the Earth's surface, in an underground environment, or from low-activity neutron sources. In this paper, we present details of its design and construction as well as its characterization with a calibrated 252Cf source and monoenergetic neutron fields of 2.5 MeV and 14 MeV. Detected monoenergetic neutron spectra are unfolded using a Singular Value Decomposition method, demonstrating a 5% energy resolution at 14 MeV. Finally, we discuss plans for measuring the surface and underground cosmogenic neutron spectra with FaNS-2. PMID:27226807

Autecological Study of the Chemoautotroph Nitrobacter by Immunofluorescence

PubMed Central

Fliermans, C. B.; Bohlool, B. B.; Schmidt, E. L.

1974-01-01

Fluorescent antibodies (FA) prepared for Nitrobacter agilis and N. winogradskyi were highly reactive in homologous staining. Low-level cross-reactions between the two species were removed by adsorption. All 15 pure-culture isolates of Nitrobacter tested reacted strongly with either N. agilis FA or N. winogradskyi FA. All pure-culture isolates from soils were determined to be N. winogradskyi; those from Mammoth Cave sediments and a cattle waste oxidation ditch were N. agilis. No cross-reaction was found in extensive tests that included five isolates of Nitrosomonas europaea and 668 heterotrophic aerobic and anaerobic bacteria isolated from soil, sewage, and cave sites. The FA preparations were used to detect Nitrobacter species in Mammoth Cave sediments, in a cattle waste oxidation ditch, and in surface waters and sediments of a river and to observe that N. winogradskyi can outgrow N. agilis in enrichment culture. Images PMID:4589121

Disrupted White Matter Microstructure and Mood Disorders after Traumatic Brain Injury.

PubMed

Spitz, Gershon; Alway, Yvette; Gould, Kate Rachel; Ponsford, Jennie L

2017-02-15

Traumatic brain injury (TBI) is associated with an elevated frequency of mood disorders that may, in part, be explained by changes in white-matter microstructure. This study is the first to examine the relationship between mood disorders and white-matter pathology in a sample of patients with mild to severe TBI using a standardized psychiatric interview. This study reports on a sub-sample of 29 individuals recruited from a large prospective study that examined the evolution of psychiatric disorders following complicated, mild to severe TBI. Individuals with TBI were also compared with 23 healthy control participants. Individuals were invited to complete the Structured Clinical Interview for DSM-IV Disorders (SCID) to diagnose psychiatric disorders. Participants who developed a mood disorder within the first 3 years were categorized into a TBI-Mood group. Diffusion tensor tractography assessed white matter microstructure using atlas-based tract-averaged and along-tract approaches. Fractional anisotropy (FA) was used as the measure of white-matter microstructure. TBI participants with and without a mood disorder did not differ in regard to injury severity and other background factors. Nevertheless, TBI participants diagnosed with a mood disorder displayed significantly lower tract-averaged FA values for the right arcuate fasciculus (p = 0.011), right inferior longitudinal fasciculus (p = 0.009), and anterior segments I (p = 0.0004) and II (p = 0.007) of the corpus callosum, as well as the left (p = 0.014) and right (p = 0.015) fronto-occipital longitudinal fasciculi. The pattern of white matter disruption identified in the current study provides further support for a neurobiological basis of post-TBI mood disorders. Greater understanding of individuals' underlying neuropathology may enable better characterization and prediction of mood disorders. Integration of neuropathology may also inform the potential efficacy of pharmacological and psychological interventions.

Methanoculleus sediminis sp. nov., a methanogen from sediments near a submarine mud volcano.

PubMed

Chen, Sheng-Chung; Chen, Mei-Fei; Lai, Mei-Chin; Weng, Chieh-Yin; Wu, Sue-Yao; Lin, Saulwood; Yang, Tsanyao F; Chen, Po-Chun

2015-07-01

A mesophilic, hydrogenotrophic methanogen, strain S3Fa(T), was isolated from sediments collected by Ocean Researcher I cruise ORI-934 in 2010 near the submarine mud volcano MV4 located at the upper slope of south-west Taiwan. The methanogenic substrates utilized by strain S3Fa(T) were formate and H2/CO2 but not acetate, secondary alcohols, methylamines, methanol or ethanol. Cells of strain S3Fa(T) were non-motile, irregular cocci, 0.5-1.0 μm in diameter. The surface-layer protein showed an Mr of 128,000.The optimum growth conditions were 37 °C, pH 7.1 and 0.17 M NaCl. The DNA G+C content of the genome of strain S3Fa(T) was 62.3 mol%. Phylogenetic analysis revealed that strain S3Fa(T) was most closely related to Methanoculleus marisnigri JR1(T) (99.3% 16S rRNA gene sequence similarity). Genome relatedness between strain S3Fa(T) and Methanoculleus marisnigri JR1(T) was computed using both genome-to-genome distance analysis (GGDA) and average nucleotide identity (ANI) with values of 46.3-55.5% and 93.08%, respectively. Based on morphological, phenotypic, phylogenetic and genomic relatedness data, it is evident that strain S3Fa(T) represents a novel species of the genus Methanoculleus, for which the name Methanoculleus sediminis sp. nov. is proposed. The type strain is S3Fa(T) ( = BCRC AR10044(T) = DSM 29354(T)).

Sex differences in associations between white matter microstructure and gonadal hormones in children and adolescents with prenatal alcohol exposure.

PubMed

Uban, K A; Herting, M M; Wozniak, J R; Sowell, E R

2017-09-01

Despite accumulating evidence from animal models demonstrating that prenatal alcohol exposure (PAE) results in life-long neuroendocrine dysregulation, very little is known on this topic among humans with fetal alcohol spectrum disorders (FASD). We expected that alterations in gonadal hormones might interfere with the typical development of white matter (WM) myelination, and in a sex-dependent manner, in human adolescents with FASD. In order to investigate this hypothesis, we used diffusion tensor imaging (DTI) to assess: 1) whether or not sex moderates the impact of PAE on WM microstructure; and 2) how gonadal hormones relate to alterations in WM microstructure in children and adolescents affected by PAE. 61 youth (9 to 16 yrs.; 49% girls; 50% PAE) participated as part of the Collaborative Initiative on Fetal Alcohol Spectrum Disorders (CIFASD). DTI scans and passive drool samples were obtained to examine neurodevelopmental associations with testosterone (T) and dehydroepiandrosterone (DHEA) levels in boys and girls, and estradiol (E2) and progesterone (P) levels in girls. Tract-based spatial statistics were utilized to generate fractional anisotropy (FA) and mean diffusivity (MD) for 9 a priori WM regions of interest (ROIs). As predicted, alterations in FA were observed in adolescents with PAE relative to controls, and these differences varied by sex. Girls with PAE exhibited lower FA (Inferior fronto-occipital and Uncinate fasciculi) while boys with PAE exhibited higher FA (Callosal body, Cingulum, Corticospinal tract, Optic radiation, Superior longitudinal fasciculus) relative to age-matched controls. When gonadal hormone levels were examined in relation to DTI measures, additional group differences in FA were revealed, demonstrating that neuroendocrine factors are associated with PAE-related brain alterations. These findings provide human evidence that PAE relates to sex-specific differences in WM microstructure, and underlying alterations in gonadal hormone function may, in part, contribute to these effects. Determining PAE-effects on neuroendocrine function among humans is an essential first step towards developing novel clinical (e.g., assessment or intervention) tools that target hormone systems to improve on-going brain development among children and adolescents with FASD. Copyright © 2017 Elsevier Ltd. All rights reserved.

Polyunsaturated fatty acids in various macroalgal species from North Atlantic and tropical seas.

PubMed

van Ginneken, Vincent J T; Helsper, Johannes P F G; de Visser, Willem; van Keulen, Herman; Brandenburg, Willem A

2011-06-22

In this study the efficacy of using marine macroalgae as a source for polyunsaturated fatty acids, which are associated with the prevention of inflammation, cardiovascular diseases and mental disorders, was investigated. The fatty acid (FA) composition in lipids from seven sea weed species from the North Sea (Ulva lactuca, Chondrus crispus, Laminaria hyperborea, Fucus serratus, Undaria pinnatifida, Palmaria palmata, Ascophyllum nodosum) and two from tropical seas (Caulerpa taxifolia, Sargassum natans) was determined using GCMS. Four independent replicates were taken from each seaweed species. Omega-3 (n-3) and omega-6 (n-6) polyunsaturated fatty acids (PUFAs), were in the concentration range of 2-14 mg/g dry matter (DM), while total lipid content ranged from 7-45 mg/g DM. The n-9 FAs of the selected seaweeds accounted for 3%-56% of total FAs, n-6 FAs for 3%-32% and n-3 FAs for 8%-63%. Red and brown seaweeds contain arachidonic (C20:4, n-6) and/or eicosapentaenoic acids (EPA, C20:5, n-3), the latter being an important "fish" FA, as major PUFAs while in green seaweeds these values are low and mainly C16 FAs were found. A unique observation is the presence of another typical "fish" fatty acid, docosahexaenoic acid (DHA, C22:6, n-3) at ≈ 1 mg/g DM in S. natans. The n-6: n-3 ratio is in the range of 0.05-2.75 and in most cases below 1.0. Environmental effects on lipid-bound FA composition in seaweed species are discussed. Marine macroalgae form a good, durable and virtually inexhaustible source for polyunsaturated fatty acids with an (n-6) FA: (n-3) FA ratio of about 1.0. This ratio is recommended by the World Health Organization to be less than 10 in order to prevent inflammatory, cardiovascular and nervous system disorders. Some marine macroalgal species, like P. palmata, contain high proportions of the "fish fatty acid" eicosapentaenoic acid (EPA, C20:5, n-3), while in S. natans also docosahexaenoic acid (DHA, C22:6, n-3) was detected.

Polyunsaturated fatty acids in various macroalgal species from north Atlantic and tropical seas

PubMed Central

2011-01-01

Background In this study the efficacy of using marine macroalgae as a source for polyunsaturated fatty acids, which are associated with the prevention of inflammation, cardiovascular diseases and mental disorders, was investigated. Methods The fatty acid (FA) composition in lipids from seven sea weed species from the North Sea (Ulva lactuca, Chondrus crispus, Laminaria hyperborea, Fucus serratus, Undaria pinnatifida, Palmaria palmata, Ascophyllum nodosum) and two from tropical seas (Caulerpa taxifolia, Sargassum natans) was determined using GCMS. Four independent replicates were taken from each seaweed species. Results Omega-3 (n-3) and omega-6 (n-6) polyunsaturated fatty acids (PUFAs), were in the concentration range of 2-14 mg/g dry matter (DM), while total lipid content ranged from 7-45 mg/g DM. The n-9 FAs of the selected seaweeds accounted for 3%-56% of total FAs, n-6 FAs for 3%-32% and n-3 FAs for 8%-63%. Red and brown seaweeds contain arachidonic (C20:4, n-6) and/or eicosapentaenoic acids (EPA, C20:5, n-3), the latter being an important "fish" FA, as major PUFAs while in green seaweeds these values are low and mainly C16 FAs were found. A unique observation is the presence of another typical "fish" fatty acid, docosahexaenoic acid (DHA, C22:6, n-3) at ≈ 1 mg/g DM in S. natans. The n-6: n-3 ratio is in the range of 0.05-2.75 and in most cases below 1.0. Environmental effects on lipid-bound FA composition in seaweed species are discussed. Conclusion Marine macroalgae form a good, durable and virtually inexhaustible source for polyunsaturated fatty acids with an (n-6) FA: (n-3) FA ratio of about 1.0. This ratio is recommended by the World Health Organization to be less than 10 in order to prevent inflammatory, cardiovascular and nervous system disorders. Some marine macroalgal species, like P. palmata, contain high proportions of the "fish fatty acid" eicosapentaenoic acid (EPA, C20:5, n-3), while in S. natans also docosahexaenoic acid (DHA, C22:6, n-3) was detected. PMID:21696609

Non-IgE-mediated gastrointestinal food allergies in children.

PubMed

Caubet, Jean-Christoph; Szajewska, Hania; Shamir, Raanan; Nowak-Węgrzyn, Anna

2017-02-01

Non-IgE-mediated gastrointestinal food allergic disorders (non-IgE-GI-FA) including food protein-induced enterocolitis syndrome (FPIES), food protein-induced enteropathy (FPE), and food protein-induced allergic proctocolitis (FPIAP) are relatively uncommon in infants and young children, but are likely under-diagnosed. Non-IgE-GI-FA have a favorable prognosis, with majority resolving by age 3-5 years. Diagnosis relies on the recognition of symptoms pattern in FPIAP and FPIES and biopsy in FPE. Further studies are needed for a better understanding of the pathomechanism, which will lead eventually to the development of diagnostic tests and treatments. Limited evidence supports the role of food allergens in subsets of constipation, gastroesophageal reflux disease, irritable bowel syndrome, and colic. The immunologic pathomechanism is not fully understood and empiric prolonged avoidance of food allergens should be limited to minimize nutrient deficiency and feeding disorders/food aversions in infants. © 2016 John Wiley & Sons A/S. Published by John Wiley & Sons Ltd.

The Evaluation of Folic Acid-Deficient or Folic Acid-Supplemented Diet in the Gestational Phase of Female Rats and in Their Adult Offspring Subjected to an Animal Model of Schizophrenia.

PubMed

Canever, L; Alves, C S V; Mastella, G; Damázio, L; Polla, J V; Citadin, S; De Luca, L A; Barcellos, A S; Garcez, M L; Quevedo, J; Budni, J; Zugno, A I

2018-03-01

Although folic acid (FA) supplementation is known to influence numerous physiological functions, especially during pregnancy, little is known about its direct effects on the mothers' health. However, this vitamin is essential for the health of the mother and for the normal growth and development of the fetus. Thus, the aim of this study was (1) to evaluate the cognitive effects and biochemical markers produced by the AIN-93 diet (control), the AIN-93 diet supplemented with different doses of FA (5, 10, and 50 mg/kg), and a FA-deficient diet during pregnancy and lactation in female mother rats (dams) and (2) to evaluate the effect of maternal diets on inflammatory parameters in the adult offspring which were subjected to an animal model of schizophrenia (SZ) induced by ketamine (Ket). Our study demonstrated through the Y-maze test that rats subjected to the FA-deficient diet showed significant deficits in spatial memory, while animals supplemented with FA (5 and 10 mg/kg) showed no deficit in spatial memory. Our results also suggest that the rats subjected to the FA-deficient diet had increased levels of carbonylated proteins in the frontal cortex and hippocampus and also increased plasma levels of homocysteine (Hcy). Folate was able to prevent cognitive impairments in the rats supplemented with FA (5 and 10 mg/kg), data which may be attributed to the antioxidant effect of the vitamin. Moreover, FA prevented protein damage and elevations in Hcy levels in the rats subjected to different doses of this vitamin (5, 10, and 50 mg/kg). We verified a significant increase of the anti-inflammatory cytokine (interleukin-4 (IL-4)) and a reduction in the plasma levels of proinflammatory cytokines (interleukin-6 (IL-6)) and TNF-α) in the dams that were subjected to the diets supplemented with FA (5, 10, and 50 mg/kg), showing the possible anti-inflammatory effects of FA during pregnancy and lactation. In general, we also found that in the adult offspring that were subjected to an animal model of SZ, FA had a protective effect in relation to the levels of IL-4, IL-6, and TNF-α, which indicates that the action of FA persisted in the adult offspring, since FA showed a lasting effect on the inflammatory response, which was similar in both the dams and their offspring. In conclusion, the importance of supplementation with FA during pregnancy and lactation should be emphasized, not only for the benefit of the offspring but also for the health of the mother. All this is due to the considerable protective effect of this vitamin against oxidative damage, cognitive impairment, hyperhomocysteinemia, immune function, and also its ability in preventing common processes in post-pregnancy stages, as well as in reducing the risks of neurodevelopmental disorders and enhancing fetal immune development.

A graphene quantum dot@Fe3O4@SiO2 based nanoprobe for drug delivery sensing and dual-modal fluorescence and MRI imaging in cancer cells.

PubMed

Su, Xiaoqian; Chan, Chunyu; Shi, Jingyu; Tsang, Ming-Kiu; Pan, Yi; Cheng, Changming; Gerile, Oudeng; Yang, Mo

2017-06-15

A novel graphene quantum dot (GQD)@Fe 3 O 4 @SiO 2 based nanoprobe was reported for targeted drug delivery, sensing, dual-modal imaging and therapy. Carboxyl-terminated GQD (C-GQD) was firstly conjugated with Fe 3 O 4 @SiO 2 and then functionalized with cancer targeting molecule folic acid (FA). DOX drug molecules were then loaded on GQD surface of Fe 3 O 4 @SiO 2 @GQD-FA nanoprobe via pi-pi stacking, which resulted in Fe 3 O 4 @SiO 2 @GQD-FA/DOX conjugates based on a FRET mechanism with GQD as donor molecules and DOX as acceptor molecules. Meanwhile, we successfully performed in vitro MRI and fluorescence imaging of living Hela cells and monitored intracellular drug release process using this Fe 3 O 4 @SiO 2 @GQD-FA/DOX nanoprobe. Cell viability study demonstrated the low cytotoxicity of Fe 3 O 4 @SiO 2 @GQD-FA nanocarrier and the enhanced therapeutic efficacy of Fe 3 O 4 @SiO 2 @GQD-FA/DOX nanoprobe for cancer cells. This luminomagnetic nanoprobe will be a potential platform for cancer accurate diagnosis and therapy. Copyright © 2016 Elsevier B.V. All rights reserved.

‘One-pot’ synthesis of multifunctional GSH-CdTe quantum dots for targeted drug delivery

NASA Astrophysics Data System (ADS)

Chen, Xiaoqin; Tang, Yajun; Cai, Bing; Fan, Hongsong

2014-06-01

A novel quantum dots-based multifunctional nanovehicle (DOX-QD-PEG-FA) was designed for targeted drug delivery, fluorescent imaging, tracking, and cancer therapy, in which the GSH-CdTe quantum dots play a key role in imaging and drug delivery. To exert curative effects, the antineoplastic drug doxorubicin hydrochloride (DOX) was loaded on the GSH-CdTe quantum dots through a condensation reaction. Meanwhile, a polyethylene glycol (PEG) shell was introduced to wrap the DOX-QD, thus stabilizing the structure and preventing clearance and drug release during systemic circulation. To actively target cancer cells and prevent the nanovehicles from being absorbed by normal cells, the nanoparticles were further decorated with folic acid (FA), allowing them to target HeLa cells that express the FA receptor. The multifunctional DOX-QD-PEG-FA conjugates were simply prepared using the ‘one pot’ method. In vitro study demonstrated that this simple, multifunctional nanovehicle can deliver DOX to the targeted cancer cells and localize the nanoparticles. After reaching the tumor cells, the FA on the DOX-QD-PEG surface allowed folate receptor recognition and increased the drug concentration to realize a higher curative effect. This novel, multifunctional DOX-QD-PEG-FA system shows great potential for tumor imaging, targeting, and therapy.

A Gas-Surface Interaction Model based on Accelerated Reactive Molecular Dynamics for Hypersonic Conditions including Thermal Conduction

DTIC Science & Technology

2012-02-28

Interaction Model based on Accelerated Reactive Molecular Dynamics for Hypersonic conditions including Thermal Conduction FA9550-09-1-0157 Schwartzentruber...Dynamics for Hypersonic Conditions including Thermal Conduction Grant/Contract Number: FA9550-09-1-0157 Program Manager: Dr. John Schmisseur PI...through the boundary layer and may chemically react with the vehicle’s thermal protection system (TPS). Many TPS materials act as a catalyst for the

Debris Hazards Due to Overloaded Conventional Construction Facades

DTIC Science & Technology

2015-12-01

NAME OF RESPONSIBLE PERSON a. REPORT b. ABSTRACT c. THIS PAGE 19b. TELEPHONE NUMBER (include area code) Standard Form 298 (Re . 8...Park, CA, USA Abstract Large blast events will fail building components, such as the façade and supporting structure. Facades present the...largest loading surface, are relatively weak, and will fail first and most violently when subjected to blast loads. The range of façade and structural

Growth of YBCO Thin Films on TiN(001) and CeO2-Coated TiN Surfaces

DTIC Science & Technology

2012-02-01

Paranthaman, E.D. Specht , D.M. Kroeger, D.K. Christen, Q. He, B. Saffian, F.A. List, D.F. Lee, P.M. Martin, C.E. Klabunde, E. Hatfield, V.K. Sikka...Appl. Phys. Lett. 69 (1996) 1795. [4] M. Paranthaman, A. Goyal, F.A. List, E.D. Specht , D.F. Lee, P.M. Martin, Q. He, D.K. Christen, D.P. Norton, J.D

Folic Acid and Grape Seed Extract Prevent Azathioprine-induced Fetal Malformations and Renal Toxicity in Rats.

PubMed

El-Ashmawy, Ibrahim M; Bayad, Aida E

2016-12-01

Azathioprine (AZA) is an important drug commonly used in the therapy of the autoimmune system disorders. It induces many hazard effects that restrict its use. The present study was designed to investigate the influence of AZA on the fetal development and renal function and its co-administration with either folic acid (FA) or grape seed extract (GSE). The effects of administration of GSE or FA on AZA toxicity by gavage simultaneously for 4 weeks were studied by determining the changes in kidney histology, the glutathione level (GSH), and lipid per oxidation content as malondialdehyde in the kidney tissue. Additionally, their effects on the fetal development were investigated. Azathioprine induced a renal damage as indicated from the pronounced changes in histological structure, a significant increase in serum urea and creatinine, and malondialdehyde content in the kidney tissue. Meanwhile, the GSH activity was significantly decreased. Co-treatment with GSE significantly minimized the previously mentioned hazard effects of AZA by ameliorating the antioxidant activity. At this point, FA induced a nonsignificant protective activity. The results also revealed that administration of FA or GSE at 6th to 15th day of gestation did not altered fetal development. While, AZA administration clearly disturbed fetal development as indicated from a significant decrease in fetal weights. Furthermore, co-administration of both drugs significantly minimized similarly the hazards of AZA on the fetal development. It may be concluded that GSE and FA are a useful remedies. Maternal administrations of either both are protective agents against AZA-induced fetal malformations. Grape seed extract was more active than FA in potentiating the antioxidative defenses for controlling AZA-induced oxidative renal damages. Copyright © 2016 John Wiley & Sons, Ltd. Copyright © 2016 John Wiley & Sons, Ltd.

Measurement of the alpha4beta2* nicotinic acetylcholine receptor ligand 2-[(18)F]Fluoro-A-85380 and its metabolites in human blood during PET investigation: a methodological study.

PubMed

Sorger, Dietlind; Becker, Georg A; Patt, Marianne; Schildan, Andreas; Grossmann, Udo; Schliebs, Reinhard; Seese, Anita; Kendziorra, Kai; Kluge, Magnus; Brust, Peter; Mukhin, Alexey G; Sabri, Osama

2007-04-01

2-[(18)F]fluoro-A-85380 (2-[(18)F]FA) is a new radioligand for noninvasive imaging of alpha4beta2* nicotinic acetylcholine receptors (nAChRs) by positron emission tomography (PET) in human brain. In most cases, quantification of 2-[(18)F]FA receptor binding involves measurement of free nonmetabolized radioligand concentration in blood. This requires an efficient and reliable method to separate radioactive metabolites from the parent compound. In the present study, three analytical methods, thin layer chromatography (TLC), high-performance liquid chromatography (HPLC) and solid phase extraction (SPE) have been tested. Reversed-phase TLC of deproteinized aqueous samples of plasma provides good estimates of 2-[(18)F]FA and its metabolites. However, because of the decreased radioactivity in plasma samples, this method can be used in humans over the first 2 h after radioligand injection only. Reliable quantification of the parent radioligand and its main metabolites was obtained using reversed-phase HPLC, followed by counting of eluted fractions in a well gamma counter. Three main and five minor metabolites of 2-[(18)F]FA were detected in human blood using this method. On average, the unchanged 2-[(18)F]FA fraction in plasma of healthy volunteers measured at 14, 60, 120, 240 and 420 min after radioligand injection was 87.3+/-2.2%, 74.4+/-3%, 68.8+/-5%, 62.3+/-8% and 61.0+/-8%, respectively. In patients with neurodegenerative disorders, the values corresponding to the three last time points were significantly lower. The fraction of nonmetabolized 2-[(18)F]FA in plasma determined using SPE did not differ significantly from that obtained by HPLC (+gamma counting) (n=73, r=.95). Since SPE is less time-consuming than HPLC and provides comparable results, we conclude that SPE appears to be the most suitable method for measurement of 2-[(18)F]FA parent fraction during PET investigations.

AluY-mediated germline deletion, duplication and somatic stem cell reversion in UBE2T defines a new subtype of Fanconi anemia.

PubMed

Virts, Elizabeth L; Jankowska, Anna; Mackay, Craig; Glaas, Marcel F; Wiek, Constanze; Kelich, Stephanie L; Lottmann, Nadine; Kennedy, Felicia M; Marchal, Christophe; Lehnert, Erik; Scharf, Rüdiger E; Dufour, Carlo; Lanciotti, Marina; Farruggia, Piero; Santoro, Alessandra; Savasan, Süreyya; Scheckenbach, Kathrin; Schipper, Jörg; Wagenmann, Martin; Lewis, Todd; Leffak, Michael; Farlow, Janice L; Foroud, Tatiana M; Honisch, Ellen; Niederacher, Dieter; Chakraborty, Sujata C; Vance, Gail H; Pruss, Dmitry; Timms, Kirsten M; Lanchbury, Jerry S; Alpi, Arno F; Hanenberg, Helmut

2015-09-15

Fanconi anemia (FA) is a rare inherited disorder clinically characterized by congenital malformations, progressive bone marrow failure and cancer susceptibility. At the cellular level, FA is associated with hypersensitivity to DNA-crosslinking genotoxins. Eight of 17 known FA genes assemble the FA E3 ligase complex, which catalyzes monoubiquitination of FANCD2 and is essential for replicative DNA crosslink repair. Here, we identify the first FA patient with biallelic germline mutations in the ubiquitin E2 conjugase UBE2T. Both mutations were aluY-mediated: a paternal deletion and maternal duplication of exons 2-6. These loss-of-function mutations in UBE2T induced a cellular phenotype similar to biallelic defects in early FA genes with the absence of FANCD2 monoubiquitination. The maternal duplication produced a mutant mRNA that could encode a functional protein but was degraded by nonsense-mediated mRNA decay. In the patient's hematopoietic stem cells, the maternal allele with the duplication of exons 2-6 spontaneously reverted to a wild-type allele by monoallelic recombination at the duplicated aluY repeat, thereby preventing bone marrow failure. Analysis of germline DNA of 814 normal individuals and 850 breast cancer patients for deletion or duplication of UBE2T exons 2-6 identified the deletion in only two controls, suggesting aluY-mediated recombinations within the UBE2T locus are rare and not associated with an increased breast cancer risk. Finally, a loss-of-function germline mutation in UBE2T was detected in a high-risk breast cancer patient with wild-type BRCA1/2. Cumulatively, we identified UBE2T as a bona fide FA gene (FANCT) that also may be a rare cancer susceptibility gene. © The Author 2015. Published by Oxford University Press.

Tetratricopeptide-motif-mediated interaction of FANCG with recombination proteins XRCC3 and BRCA2.

PubMed

Hussain, Shobbir; Wilson, James B; Blom, Eric; Thompson, Larry H; Sung, Patrick; Gordon, Susan M; Kupfer, Gary M; Joenje, Hans; Mathew, Christopher G; Jones, Nigel J

2006-05-10

Fanconi anaemia is an inherited chromosomal instability disorder characterised by cellular sensitivity to DNA interstrand crosslinkers, bone-marrow failure and a high risk of cancer. Eleven FA genes have been identified, one of which, FANCD1, is the breast cancer susceptibility gene BRCA2. At least eight FA proteins form a nuclear core complex required for monoubiquitination of FANCD2. The BRCA2/FANCD1 protein is connected to the FA pathway by interactions with the FANCG and FANCD2 proteins, both of which co-localise with the RAD51 recombinase, which is regulated by BRCA2. These connections raise the question of whether any of the FANC proteins of the core complex might also participate in other complexes involved in homologous recombination repair. We therefore tested known FA proteins for direct interaction with RAD51 and its paralogs XRCC2 and XRCC3. FANCG was found to interact with XRCC3, and this interaction was disrupted by the FA-G patient derived mutation L71P. FANCG was co-immunoprecipitated with both XRCC3 and BRCA2 from extracts of human and hamster cells. The FANCG-XRCC3 and FANCG-BRCA2 interactions did not require the presence of other FA proteins from the core complex, suggesting that FANCG also participates in a DNA repair complex that is downstream and independent of FANCD2 monoubiquitination. Additionally, XRCC3 and BRCA2 proteins co-precipitate in both human and hamster cells and this interaction requires FANCG. The FANCG protein contains multiple tetratricopeptide repeat motifs (TPRs), which function as scaffolds to mediate protein-protein interactions. Mutation of one or more of these motifs disrupted all of the known interactions of FANCG. We propose that FANCG, in addition to stabilising the FA core complex, may have a role in building multiprotein complexes that facilitate homologous recombination repair.

FANCA Gene Mutations with 8 Novel Molecular Changes in Indian Fanconi Anemia Patients.

PubMed

Solanki, Avani; Mohanty, Purvi; Shukla, Pallavi; Rao, Anita; Ghosh, Kanjaksha; Vundinti, Babu Rao

2016-01-01

Fanconi anemia (FA), a rare heterogeneous genetic disorder, is known to be associated with 19 genes and a spectrum of clinical features. We studied FANCA molecular changes in 34 unrelated and 2 siblings of Indian patients with FA and have identified 26 different molecular changes of FANCA gene, of which 8 were novel mutations (a small deletion c.2500delC, 4 non-sense mutations c.2182C>T, c.2630C>G, c.3677C>G, c.3189G>A; and 3 missense mutations; c.1273G>C, c.3679 G>C, and c.3992 T>C). Among these only 16 patients could be assigned FA-A complementation group, because we could not confirm single exon deletions detected by MLPA or cDNA amplification by secondary confirmation method and due to presence of heterozygous non-pathogenic variations or heterozygous pathogenic mutations. An effective molecular screening strategy should be developed for confirmation of these mutations and determining the breakpoints for single exon deletions.

FANCA Gene Mutations with 8 Novel Molecular Changes in Indian Fanconi Anemia Patients

PubMed Central

Solanki, Avani; Mohanty, Purvi; Shukla, Pallavi; Rao, Anita; Ghosh, Kanjaksha; Vundinti, Babu Rao

2016-01-01

Fanconi anemia (FA), a rare heterogeneous genetic disorder, is known to be associated with 19 genes and a spectrum of clinical features. We studied FANCA molecular changes in 34 unrelated and 2 siblings of Indian patients with FA and have identified 26 different molecular changes of FANCA gene, of which 8 were novel mutations (a small deletion c.2500delC, 4 non-sense mutations c.2182C>T, c.2630C>G, c.3677C>G, c.3189G>A; and 3 missense mutations; c.1273G>C, c.3679 G>C, and c.3992 T>C). Among these only 16 patients could be assigned FA-A complementation group, because we could not confirm single exon deletions detected by MLPA or cDNA amplification by secondary confirmation method and due to presence of heterozygous non-pathogenic variations or heterozygous pathogenic mutations. An effective molecular screening strategy should be developed for confirmation of these mutations and determining the breakpoints for single exon deletions. PMID:26799702

Immobilization free electrochemical biosensor for folate receptor in cancer cells based on terminal protection.

PubMed

Ni, Jiancong; Wang, Qingxiang; Yang, Weiqiang; Zhao, Mengmeng; Zhang, Ying; Guo, Longhua; Qiu, Bin; Lin, Zhenyu; Yang, Huang-Hao

2016-12-15

The determination of folate receptor (FR) that over expressed in vast quantity of cancerous cells frequently is significant for the clinical diagnosis and treatment of cancers. Many DNA-based electrochemical biosensors have been developed for FR detection with high selectivity and sensitivity, but most of them need complicated immobilization of DNA on the electrode surface firstly, which is tedious and therefore results in the poor reproducibility. In this study, a simple, sensitive, and selective electrochemical FR biosensor in cancer cells has been proposed, which combines the advantages of the convenient immobilization-free homogeneous indium tin oxide (ITO)-based electrochemical detection strategy and the high selectivity of the terminal protection of small molecule linked DNA. The small molecule of folic acid (FA) and an electroactive molecule of ferrocence (Fc) were tethered to 3'- and 5'-end of an arbitrary single-stranded DNA (ssDNA), respectively, forming the FA-ssDNA-Fc complex. In the absence of the target FR, the FA-ssDNA-Fc was degraded by exonuclease I (Exo I) from 3'-end and produced a free Fc, diffusing freely to the ITO electrode surface and resulting in strong electrochemical signal. When the target FR was present, the FA-ssDNA-Fc was bound to FR through specific interaction with FA anchored at the 3'-end, effectively protecting the ssDNA strand from hydrolysis by Exo I. The FR-FA-ssDNA-Fc could not diffuse easily to the negatively charged ITO electrode surface due to the electrostatic repulsion between the DNA strand and the negatively charged ITO electrode, so electrochemical signal reduced. The decreased electrochemical signal has a linear relationship with the logarithm of FR concentration in range of 10fM to 10nM with a detection limit of 3.8fM (S/N=3). The proposed biosensor has been applied to detect FR in HeLa cancer cells, and the decreased electrochemical signal has a linear relationship with the logarithm of cell concentration ranging from 100-10000cell/mL. Compared with the traditional heterogeneous electrochemical FR biosensors, the proposed biosensor owns the merits of the simplicity and high specificity, presenting the great potential application in the area of early diagnosis of cancers. Copyright © 2016 Elsevier B.V. All rights reserved.

Ferulic acid ameliorates TNBS-induced ulcerative colitis through modulation of cytokines, oxidative stress, iNOs, COX-2, and apoptosis in laboratory rats

PubMed Central

Sadar, Smeeta S.; Vyawahare, Niraj S.; Bodhankar, Subhash L.

2016-01-01

Ulcerative colitis (UC) is a chronic immune-inflammatory disorder characterized by oxido-nitrosative stress, the release of pro-inflammatory cytokines and apoptosis. Ferulic acid (FA), a phenolic compound is considered to possess potent antioxidant, anti-apoptotic and anti-inflammatory activities. The aim is to evaluate possible mechanism of action of FA against trinitrobenzensulfonic acid (TNBS) induced ulcerative colitis (UC) in rats. UC was induced in Sprague-Dawley rats (150-200 g) by intrarectal administration of TNBS (100 mg/kg). FA was administered (10, 20 and 40 mg/kg, p.o.) for 14 days after colitis was induced. Various biochemical, molecular and histological changes were assessed in the colon. Intrarectal administration of TNBS caused significant induction of ulcer in the colon with an elevation of oxido-nitrosative stress, myeloperoxidase and hydroxyproline activity in the colon. Administration of FA (20 and 40 mg/kg) significantly decrease oxido-nitrosative stress, myeloperoxidase, and hydroxyproline activities. Up-regulated mRNA expression of TNF-α, IL-1β, IL-6, COX-2, and iNOs, as well as down-regulated IL-10 mRNA expressions after TNBS administration, were significantly inhibited by FA (20 and 40 mg/kg) treatment. Flow cytometric analysis revealed that intrarectal administration of TNBS-induced significantly enhanced the colonic apoptosis whereas administration of FA (20 and 40 mg/kg) significantly restored the elevated apoptosis. FA administration also significantly restored the histopathological aberration induced by TNBS. The findings of the present study demonstrated that FA ameliorates TNBS-induced colitis via inhibition of oxido-nitrosative stress, apoptosis, proinflammatory cytokines production, and down- regulation of COX-2 synthesis. Graphical Abstract: TNBS caused activation of T cells which interact with CD40 on antigen presenting cells i.e. dendritic cells (DC) that induce the key Interleukin 12 (IL-12)-mediated Th1 T cell immune inflammatory response. It releases interferon-γ (IFN-γ), which in turn induces macrophages (MAC) to produce TNF-α and other pro-inflammatory cytokines (e.g., IL-1β, IL-6). This inflammatory influx resulted in induction of ulcerative colitis (UC). Administration of FA may inhibit this IFN-γ induced inflammatory cascade via a decrease in the release of pro-inflammatory cytokines to ameliorate TNBS-induced colitis. PMID:27822176

Impact of innate immunity in a subset of children with autism spectrum disorders: a case control study

PubMed Central

Jyonouchi, Harumi; Geng, Lee; Cushing-Ruby, Agnes; Quraishi, Huma

2008-01-01

Background Among patients with autism spectrum disorders (ASD) evaluated in our clinic, there appears to be a subset that can be clinically distinguished from other ASD children because of frequent infections (usually viral) accompanied by worsening behavioural symptoms and/or loss/decrease in acquired skills. This study assessed whether these clinical features of this ASD subset are associated with atopy, asthma, food allergy (FA), primary immunodeficiency (PID), or innate immune responses important in viral infections. Methods This study included the ASD children described above (ASD test, N = 26) and the following controls: ASD controls (N = 107), non-ASD controls with FA (N = 24), non-ASD controls with chronic rhinosinusitis/recurrent otitis media (CRS/ROM; N = 38), and normal controls (N = 43). We assessed prevalence of atopy, asthma, FA, CRS/ROM, and PID. Innate immune responses were assessed by measuring production of proinflammatory and counter-regulatory cytokines by peripheral blood mononuclear cells (PBMCs) in response to agonists of Toll-like receptors (TLRs), with or without pre-treatment of lipopolysaccharide (LPS), a TLR4 agonist. Results Non-IgE mediated FA was equally prevalent in both ASD test and ASD control groups, occurring at higher frequency than in the non-ASD controls. Allergic rhinitis, atopic/non-atopic asthma, and atopic dermatitis were equally prevalent among the study groups except for the CRS/ROM group in which non-atopic asthma was more prevalent (52.6%). CRS/ROM and specific polysaccharide antibody deficiency (SPAD) were more prevalent in the ASD test group than in the ASD control, FA, and normal control groups: 23.1% vs. < 5% for CRS/ROS and 19.2% vs. < 1% for SPAD. However, CRS/ROM patients had the highest prevalence of SPAD (34.2%). When compared to ASD and normal case controls, PBMCs from 19 non-SPAD, ASD test group children produced: 1) less IL-1β with a TLR7/8 agonist, less IL-10 with a TLR2/6 agonist, and more IL-23 with a TLR4 agonist without LPS pre-treatment, and 2) less IL-1β with TLR4/7/8 agonists with LPS pre-treatment. These are cytokines associated with the neuro-immune network. Conclusion Clinical features of the ASD test group were not associated with atopy, asthma, FA, or PID in our study but may be associated with altered TLR responses mediating neuro-immune interactions. PMID:19025588

Influence of two types of organic matter on interaction of CeO2 nanoparticles with plants in hydroponic culture.

PubMed

Schwabe, Franziska; Schulin, Rainer; Limbach, Ludwig K; Stark, Wendelin; Bürge, Diane; Nowack, Bernd

2013-04-01

An important aspect in risk assessment of nanoparticles (NPs) is to understand their environmental interactions. We used hydroponic plant cultures to study nanoparticle-plant-root interaction and translocation and exposed wheat and pumpkin to suspensions of uncoated CeO2-NP for 8d (primary particle size 17-100 nm, 100 mg L(-1)) in the absence and presence of fulvic acid (FA) and gum arabic (GA) as representatives of different types of natural organic matter. The behavior of CeO2-NPs in the hydroponic solution was monitored regarding agglomeration, sedimentation, particle size distribution, surface charge, amounts of root association, and translocation into shoots. NP-dispersions were stable over 8d in the presence of FA or GA, but with growing plants, changes in pH, particle agglomeration rate, and hydrodynamic diameter were observed. None of the plants exhibited reduced growth or any toxic response during the experiment. We found that CeO2-NPs translocated into pumpkin shoots, whereas this did not occur in wheat plants. The presence of FA and GA affected the amount of CeO2 associated with roots (pure>FA>GA) but did not affect the translocation factor. Additionally, we could confirm via TEM and SEM that CeO2-NPs adhered strongly to root surfaces of both plant species. Copyright © 2013 Elsevier Ltd. All rights reserved.

Miniaturised enzymatic conductometric biosensor with Nafion membrane for the direct determination of formaldehyde in water samples.

PubMed

Nguyen-Boisse, Thanh-Thuy; Saulnier, Joëlle; Jaffrezic-Renault, Nicole; Lagarde, Florence

2014-02-01

A new conductometric enzyme-based biosensor was developed for the determination of formaldehyde (FA) in aqueous solutions. The biosensor was prepared by cross-linking formaldehyde dehydrogenase from Pseudomonas putida with bovine serum albumin in saturated glutaraldehyde vapours (GA) at the surface of interdigitated gold microelectrodes. Nicotinamide adenine dinucleotide cofactor (NAD(+)) was added in solution at each measurement to maintain enzyme activity. Addition of a Nafion layer over the enzyme modified electrode resulted in a significant increase of biosensor signal due to enhanced accumulation of protons generated by enzymatic reaction at the electrode surface. Different parameters affecting enzyme activity or playing a role in ionic transfer through the Nafion membrane were optimised. In optimal conditions (0.045 mg enzyme, 30 min exposure to GA, 0.3 μL of a 1% (v/v) Nafion solution deposit, measurement in 5 mM phosphate buffer pH 7 containing 20 μM NAD(+)), the biosensor signal was linear up to 10 mM FA, and the detection limit was 18 μM. Relative standard deviations calculated from five consecutive replicates of FA solutions were lower than 5% in the 1-10 mM range. The biosensor was successfully applied to the determination of FA in spiked water samples (tap water and Rhone river water), with recoveries in the 95-110% range.

Deletion and reduced expression of the Fanconi anemia FANCA gene in sporadic acute myeloid leukemia.

PubMed

Tischkowitz, M D; Morgan, N V; Grimwade, D; Eddy, C; Ball, S; Vorechovsky, I; Langabeer, S; Stöger, R; Hodgson, S V; Mathew, C G

2004-03-01

Fanconi anemia (FA) is an autosomal recessive chromosomal instability disorder caused by mutations in one of seven known genes (FANCA,C,D2,E,F,G and BRCA2). Mutations in the FANCA gene are the most prevalent, accounting for two-thirds of FA cases. Affected individuals have greatly increased risks of acute myeloid leukemia (AML). This raises the question as to whether inherited or acquired mutations in FA genes might be involved in the development of sporadic AML. Quantitative fluorescent PCR was used to screen archival DNA from sporadic AML cases for FANCA deletions, which account for 40% of FANCA mutations in FA homozygotes. Four heterozygous deletions were found in 101 samples screened, which is 35-fold higher than the expected population frequency for germline FANCA deletions (P<0.0001). Sequencing FANCA in the AML samples with FANCA deletions did not detect mutations in the second allele and there was no evidence of epigenetic silencing by hypermethylation. However, real-time quantitative PCR analysis in these samples showed reduced expression of FANCA compared to nondeleted AML samples and to controls. These findings suggest that gene deletions and reduced expression of FANCA may be involved in the promotion of genetic instability in a subset of cases of sporadic AML.

FANCA knockout in human embryonic stem cells causes a severe growth disadvantage.

PubMed

Vanuytsel, Kim; Cai, Qing; Nair, Nisha; Khurana, Satish; Shetty, Swati; Vermeesch, Joris R; Ordovas, Laura; Verfaillie, Catherine M

2014-09-01

Fanconi anemia (FA) is an autosomal recessive disorder characterized by progressive bone marrow failure (BMF) during childhood, aside from numerous congenital abnormalities. FA mouse models have been generated; however, they do not fully mimic the hematopoietic phenotype. As there is mounting evidence that the hematopoietic impairment starts already in utero, a human pluripotent stem cell model would constitute a more appropriate system to investigate the mechanisms underlying BMF in FA and its developmental basis. Using zinc finger nuclease (ZFN) technology, we have created a knockout of FANCA in human embryonic stem cells (hESC). We introduced a selection cassette into exon 2 thereby disrupting the FANCA coding sequence and found that whereas mono-allelically targeted cells retain an unaltered proliferation potential, disruption of the second allele causes a severe growth disadvantage. As a result, heterogeneous cultures arise due to the presence of cells still carrying an unaffected FANCA allele, quickly outgrowing the knockout cells. When pure cultures of FANCA knockout hESC are pursued either through selection or single cell cloning, this rapidly results in growth arrest and such cultures cannot be maintained. These data highlight the importance of a functional FA pathway at the pluripotent stem cell stage. Copyright © 2014. Published by Elsevier B.V.

Upregulated LINE-1 Activity in the Fanconi Anemia Cancer Susceptibility Syndrome Leads to Spontaneous Pro-inflammatory Cytokine Production.

PubMed

Brégnard, Christelle; Guerra, Jessica; Déjardin, Stéphanie; Passalacqua, Frank; Benkirane, Monsef; Laguette, Nadine

2016-06-01

Fanconi Anemia (FA) is a genetic disorder characterized by elevated cancer susceptibility and pro-inflammatory cytokine production. Using SLX4(FANCP) deficiency as a working model, we questioned the trigger for chronic inflammation in FA. We found that absence of SLX4 caused cytoplasmic DNA accumulation, including sequences deriving from active Long INterspersed Element-1 (LINE-1), triggering the cGAS-STING pathway to elicit interferon (IFN) expression. In agreement, absence of SLX4 leads to upregulated LINE-1 retrotransposition. Importantly, similar results were obtained with the FANCD2 upstream activator of SLX4. Furthermore, treatment of FA cells with the Tenofovir reverse transcriptase inhibitor (RTi), that prevents endogenous retrotransposition, decreased both accumulation of cytoplasmic DNA and pro-inflammatory signaling. Collectively, our data suggest a contribution of endogenous RT activities to the generation of immunogenic cytoplasmic nucleic acids responsible for inflammation in FA. The additional observation that RTi decreased pro-inflammatory cytokine production induced by DNA replication stress-inducing drugs further demonstrates the contribution of endogenous RTs to sustaining chronic inflammation. Altogether, our data open perspectives in the prevention of adverse effects of chronic inflammation in tumorigenesis. Copyright © 2016 The Authors. Published by Elsevier B.V. All rights reserved.

Risk of Human Papillomavirus Infection in Cancer-Prone Individuals: What We Know

PubMed Central

Khoury, Ruby; Sauter, Sharon; Butsch Kovacic, Melinda; Nelson, Adam S.; Myers, Kasiani C.; Mehta, Parinda A.; Davies, Stella M.; Wells, Susanne I.

2018-01-01

Human papillomavirus (HPV) infections cause a significant proportion of cancers worldwide, predominantly squamous cell carcinomas (SCC) of the mucosas and skin. High-risk HPV types are associated with SCCs of the anogenital and oropharyngeal tract. HPV oncogene activities and the biology of SCCs have been intensely studied in laboratory models and humans. What remains largely unknown are host tissue and immune-related factors that determine an individual’s susceptibility to infection and/or carcinogenesis. Such susceptibility factors could serve to identify those at greatest risk and spark individually tailored HPV and SCC prevention efforts. Fanconi anemia (FA) is an inherited DNA repair disorder that is in part characterized by extreme susceptibility to SCCs. An increased prevalence of HPV has been reported in affected individuals, and molecular and functional connections between FA, SCC, and HPV were established in laboratory models. However, the presence of HPV in some human FA tumors is controversial, and the extent of the etiological connections remains to be established. Herein, we discuss cellular, immunological, and phenotypic features of FA, placed into the context of HPV pathogenesis. The goal is to highlight this orphan disease as a unique model system to uncover host genetic and molecular HPV features, as well as SCC susceptibility factors. PMID:29361695

Subgenual Cingulum Microstructure Supports Control of Emotional Conflict.

PubMed

Keedwell, Paul A; Doidge, Amie N; Meyer, Marcel; Lawrence, Natalia; Lawrence, Andrew D; Jones, Derek K

2016-06-01

Major depressive disorder (MDD) is associated with specific difficulties in attentional disengagement from negatively valenced material. Diffusion MRI studies have demonstrated altered white matter microstructure in the subgenual cingulum bundle (CB) in individuals with MDD, though the functional significance of these alterations has not been examined formally. This study explored whether individual differences in selective attention to negatively valenced stimuli are related to interindividual differences in subgenual CB microstructure. Forty-six individuals (21 with remitted MDD, 25 never depressed) completed an emotional Stroop task, using happy and angry distractor faces overlaid by pleasant or unpleasant target words and a control gender-based Stroop task. CBs were reconstructed in 38 individuals using diffusion-weighted imaging and tractography, and mean fractional anisotropy (FA) computed for the subgenual, retrosplenial, and parahippocampal subdivisions. No significant correlations were found between FA and performance in the control gender-based Stroop task in any CB region. However, the degree of interference produced by angry face distractors on time to identify pleasant words (emotional conflict) correlated selectively with FA in the subgenual CB (r = -0.53; P = 0.01). Higher FA was associated with reduced interference, irrespective of a diagnosis of MDD, suggesting that subgenual CB microstructure is functionally relevant for regulating attentional bias toward negative interpersonal stimuli. © The Author 2016. Published by Oxford University Press.

A diffusion tensor imaging study of suicide attempters

PubMed Central

Thapa-Chhetry, Binod; Sublette, M. Elizabeth; Sullivan, Gregory M.; Oquendo, Maria A.; Mann, J. John; Parsey, Ramin V.

2014-01-01

Background Few studies have examined white matter abnormalities in suicide attempters using diffusion tensor imaging (DTI). This study sought to identify white matter regions altered in individuals with a prior suicide attempt. Methods DTI scans were acquired in 13 suicide attempters with major depressive disorder (MDD), 39 non-attempters with MDD, and 46 healthy participants (HP). Fractional anisotropy (FA) and apparent diffusion coefficient (ADC) was determined in the brain using two methods: region of interest (ROI) and tract-based spatial statistics (TBSS). ROIs were limited a priori to white matter adjacent to the caudal anterior cingulate cortex, rostral anterior cingulate cortex, dorsomedial prefrontal cortex, and medial orbitofrontal cortex. Results Using the ROI approach, suicide attempters had lower FA than MDD non-attempters and HP in the dorsomedial prefrontal cortex. Uncorrected TBSS results confirmed a significant cluster within the right dorsomedial prefrontal cortex indicating lower FA in suicide attempters compared to non-attempters. There were no differences in ADC when comparing suicide attempters, non-attempters and HP groups using ROI or TBSS methods. Conclusions Low FA in the dorsomedial prefrontal cortex was associated with a suicide attempt history. Converging findings from other imaging modalities support this finding, making this region of potential interest in determining the diathesis for suicidal behavior. PMID:24462041

Subgenual Cingulum Microstructure Supports Control of Emotional Conflict

PubMed Central

Keedwell, Paul A.; Doidge, Amie N.; Meyer, Marcel; Lawrence, Natalia; Lawrence, Andrew D.; Jones, Derek K.

2016-01-01

Major depressive disorder (MDD) is associated with specific difficulties in attentional disengagement from negatively valenced material. Diffusion MRI studies have demonstrated altered white matter microstructure in the subgenual cingulum bundle (CB) in individuals with MDD, though the functional significance of these alterations has not been examined formally. This study explored whether individual differences in selective attention to negatively valenced stimuli are related to interindividual differences in subgenual CB microstructure. Forty-six individuals (21 with remitted MDD, 25 never depressed) completed an emotional Stroop task, using happy and angry distractor faces overlaid by pleasant or unpleasant target words and a control gender-based Stroop task. CBs were reconstructed in 38 individuals using diffusion-weighted imaging and tractography, and mean fractional anisotropy (FA) computed for the subgenual, retrosplenial, and parahippocampal subdivisions. No significant correlations were found between FA and performance in the control gender-based Stroop task in any CB region. However, the degree of interference produced by angry face distractors on time to identify pleasant words (emotional conflict) correlated selectively with FA in the subgenual CB (r = −0.53; P = 0.01). Higher FA was associated with reduced interference, irrespective of a diagnosis of MDD, suggesting that subgenual CB microstructure is functionally relevant for regulating attentional bias toward negative interpersonal stimuli. PMID:27048427

Complement-fixing Activity of Fulvic Acid from Shilajit and Other Natural Sources

PubMed Central

Schepetkin, Igor A.; Xie, Gang; Jutila, Mark A.; Quinn, Mark T.

2008-01-01

Shilajit has been used traditionally in folk medicine for treatment of a variety of disorders, including syndromes involving excessive complement activation. Extracts of Shilajit contain significant amounts of fulvic acid (FA), and it has been suggested that FA is responsible for many therapeutic properties of Shilajit. However, little is known regarding physical and chemical properties of Shilajit extracts, and nothing is known about their effects on the complement system. To address this issue, we fractionated extracts of commercial Shilajit using anion exchange and size-exclusion chromatography. One neutral (S-I) and two acidic (S-II and S-III) fractions were isolated, characterized, and compared with standardized FA samples. The most abundant fraction (S-II) was further fractionated into three sub-fractions (S-II-1 to S-II-3). The van Krevelen diagram showed that the Shilajit fractions are products of polysaccharide degradation, and all fractions, except S-II-3, contained type II arabinogalactan. All Shilajit fractions exhibited dose-dependent complement-fixing activity in vitro with high potency. Furthermore, we found a strong correlation between complement-fixing activity and carboxylic group content in the Shilajit fractions and other FA sources. These data provide a molecular basis to explain at least part of the beneficial therapeutic properties of Shilajit and other humic extracts. PMID:19107845

The identification of FANCD2 DNA binding domains reveals nuclear localization sequences.

PubMed

Niraj, Joshi; Caron, Marie-Christine; Drapeau, Karine; Bérubé, Stéphanie; Guitton-Sert, Laure; Coulombe, Yan; Couturier, Anthony M; Masson, Jean-Yves

2017-08-21

Fanconi anemia (FA) is a recessive genetic disorder characterized by congenital abnormalities, progressive bone-marrow failure, and cancer susceptibility. The FA pathway consists of at least 21 FANC genes (FANCA-FANCV), and the encoded protein products interact in a common cellular pathway to gain resistance against DNA interstrand crosslinks. After DNA damage, FANCD2 is monoubiquitinated and accumulates on chromatin. FANCD2 plays a central role in the FA pathway, using yet unidentified DNA binding regions. By using synthetic peptide mapping and DNA binding screen by electromobility shift assays, we found that FANCD2 bears two major DNA binding domains predominantly consisting of evolutionary conserved lysine residues. Furthermore, one domain at the N-terminus of FANCD2 bears also nuclear localization sequences for the protein. Mutations in the bifunctional DNA binding/NLS domain lead to a reduction in FANCD2 monoubiquitination and increase in mitomycin C sensitivity. Such phenotypes are not fully rescued by fusion with an heterologous NLS, which enable separation of DNA binding and nuclear import functions within this domain that are necessary for FANCD2 functions. Collectively, our results enlighten the importance of DNA binding and NLS residues in FANCD2 to activate an efficient FA pathway. © The Author(s) 2017. Published by Oxford University Press on behalf of Nucleic Acids Research.

Altered White Matter Integrity in Human Immunodeficiency Virus-Associated Neurocognitive Disorder: A Tract-Based Spatial Statistics Study.

PubMed

Oh, Se Won; Shin, Na-Young; Choi, Jun Yong; Lee, Seung-Koo; Bang, Mi Rim

2018-01-01

Human immunodeficiency virus (HIV) infection has been known to damage the microstructural integrity of white matter (WM). However, only a few studies have assessed the brain regions in HIV-associated neurocognitive disorders (HAND) with diffusion tensor imaging (DTI). Therefore, we sought to compare the DTI data between HIV patients with and without HAND using tract-based spatial statistics (TBSS). Twenty-two HIV-infected patients (10 with HAND and 12 without HAND) and 11 healthy controls (HC) were enrolled in this study. A whole-brain analysis of fractional anisotropy (FA), mean diffusivity (MD), radial diffusivity (RD), and axial diffusivity was performed with TBSS and a subsequent 20 tract-specific region-of-interest (ROI)-based analysis to localize and compare altered WM integrity in all group contrasts. Compared with HC, patients with HAND showed decreased FA in the right frontoparietal WM including the upper corticospinal tract (CST) and increased MD and RD in the bilateral frontoparietal WM, corpus callosum, bilateral CSTs and bilateral cerebellar peduncles. The DTI values did not significantly differ between HIV patients with and without HAND or between HIV patients without HAND and HC. In the ROI-based analysis, decreased FA was observed in the right superior longitudinal fasciculus and was significantly correlated with decreased information processing speed, memory, executive function, and fine motor function in HIV patients. These results suggest that altered integrity of the frontoparietal WM contributes to cognitive dysfunction in HIV patients.

Coal fly ash as a source of iron in atmospheric dust.

PubMed

Chen, Haihan; Laskin, Alexander; Baltrusaitis, Jonas; Gorski, Christopher A; Scherer, Michelle M; Grassian, Vicki H

2012-02-21

Anthropogenic coal fly ash (FA) aerosol may represent a significant source of bioavailable iron in the open ocean. Few measurements have been made that compare the solubility of atmospheric iron from anthropogenic aerosols and other sources. We report here an investigation of iron dissolution for three FA samples in acidic aqueous solutions and compare the solubilities with that of Arizona test dust (AZTD), a reference material for mineral dust. The effects of pH, simulated cloud processing, and solar radiation on iron solubility have been explored. Similar to previously reported results on mineral dust, iron in aluminosilicate phases provides the predominant component of dissolved iron. Iron solubility of FA is substantially higher than of the crystalline minerals comprising AZTD. Simulated atmospheric processing elevates iron solubility due to significant changes in the morphology of aluminosilicate glass, a dominant material in FA particles. Iron is continuously released into the aqueous solution as FA particles break up into smaller fragments. These results suggest that the assessment of dissolved atmospheric iron deposition fluxes and their effect on the biogeochemistry at the ocean surface should be constrained by the source, environmental pH, iron speciation, and solar radiation.

Superparamagnetic Fe3O4-PEG2K-FA@Ce6 Nanoprobes for in Vivo Dual-mode Imaging and Targeted Photodynamic Therapy

NASA Astrophysics Data System (ADS)

Yin, Ting; Huang, Peng; Gao, Guo; Shapter, Joseph G.; Shen, Yulan; Sun, Rongjin; Yue, Caixia; Zhang, Chunlei; Liu, Yanlei; Zhou, Sui; Cui, Daxiang

2016-11-01

The development of targeted nanoprobes is a promising approach to cancer diagnostics and therapy. In the present work, a novel multifunctional photo/magnet-diagnostic nanoprobe (MNPs-PEG2K-FA@Ce6) has been developed. This nanoprobe is built using folic acid (FA), bifunctional polyethylene glycol (PEG2K) and photosensitizer chlorin e6 (Ce6). The MNPs-PEG2K-FA@Ce6 nanoprobes are superparamagnetic, can be synthesized on a large scale by a one-pot hydrothermal process without further surface modification and are stable in an aqueous environment for eight months. Compared with free Ce6 nanoprobes in vitro studies, the MNPs-PEG2K-FA@Ce6 nanoprobes significantly enhance cellular uptake efficiency and promote the effectiveness of photodynamic therapy (PDT) with the assistance of 633 nm laser irradiation. The unique nanoprobes show superior penetration and a retention time of more than six days with less accumulation in the liver allowing highly effective tumor recognition and monitoring. Additionally, there was little damage to healthy organs or tissues. These exciting new nanoprobes could be potential building blocks to develop new clinical therapies and translational medicine.

Trophic ecology of two cold-water coral species from the Mediterranean Sea revealed by lipid biomarkers and compound-specific isotope analyses

NASA Astrophysics Data System (ADS)

Naumann, Malik S.; Tolosa, Imma; Taviani, Marco; Grover, Renaud; Ferrier-Pagès, Christine

2015-12-01

Scleractinian cold-water corals (CWC) act as key ecosystem engineers in deep-sea reef environments worldwide. However, our current understanding of their trophic ecology is still limited, particularly in understudied temperate oceanic regions such as the Mediterranean Sea. Hence, this study investigated the trophic ecology of the CWC Desmophyllum dianthus and Madrepora oculata by employing lipid biomarker techniques and compound-specific isotope analyses on coral tissues, suspended particulate organic matter (sPOM), and surface sediment sampled in a Mediterranean CWC habitat. CWC exhibited high contents of poly- and monounsaturated fatty acids (FA) (≥49 and 32 % of FA, respectively) and cholesterol (≥67 % of sterols), while sPOM and sediment samples were enriched in saturated FA (≥44 % of FA) and sitosterol (≥35 % of sterols). CWC contained some rare very long-chained polyunsaturated FA (>C22) and ergosterol absent in sPOM and sediment samples. Our results indicate that Mediterranean CWC mainly consume living food items, rather than detrital sPOM or resuspended sediment, and provide evidence for preferred feeding on omnivorous and carnivorous zooplankton. Overall, these findings provide new insights to the trophic ecology of two common CWC from the Mediterranean Sea.

Characterization of heavy-metal-contaminated sediment by using unsupervised multivariate techniques and health risk assessment.

PubMed

Wang, Yeuh-Bin; Liu, Chen-Wuing; Wang, Sheng-Wei

2015-03-01

This study characterized the sediment quality of the severely contaminated Erjen River in Taiwan by using multivariate analysis methods-including factor analysis (FA), self-organizing maps (SOMs), and positive matrix factorization (PMF)-and health risk assessment. The SOMs classified the dataset with similar heavy-metal-contaminated sediment into five groups. FA extracted three major factors-traditional electroplating and metal-surface processing factor, nontraditional heavy-metal-industry factor, and natural geological factor-which accounted for 80.8% of the variance. The SOMs and FA revealed the heavy-metal-contaminated-sediment hotspots in the middle and upper reaches of the major tributary in the dry season. The hazardous index value for health risk via ingestion was 0.302. PMF further qualified the source apportionment, indicating that traditional electroplating and metal-surface-processing industries comprised 47% of the health risk posed by heavy-metal-contaminated sediment. Contaminants discharged from traditional electroplating and metal-surface-processing industries in the middle and upper reaches of the major tributary must be eliminated first to improve the sediment quality in Erjen River. The proposed assessment framework for heavy-metal-contaminated sediment can be applied to contaminated-sediment river sites in other regions. Copyright © 2014 Elsevier Inc. All rights reserved.

Effect of FA/O complexing agents and H2O2 on chemical mechanical polishing of ruthenium in weakly alkaline slurry

NASA Astrophysics Data System (ADS)

Bo, Duan; Weijing, An; Jianwei, Zhou; Shuai, Wang

2015-07-01

This paper investigated the effect of FA/O and hydrogen peroxide (H2O2) on ruthenium (Ru) removal rate (RR) and static etching rate (SER). It was revealed that Ru RR and SER first linearly increased then slowly decreaseed with the increasing H2O2 probably due to the formation of uniform Ru oxides on the surface during polishing. Their corrosion behaviors and states of surface oxidation were analyzed. In addition, FA/O could chelate Ru oxides (such as (RuO4)2- and RuO4- changed into soluble amine salts [R(NH3)4] (RuO4)2) and enhance Ru RR. The non-ionic surfactant AD was used to improve the Ru CMP performance. In particular, the addition of AD can lead to significant improvement of the surface roughness. Project supported by the Special Project Items No. 2 in National Long-Term Technology Development Plan (No. 2009ZX02308), the Natural Science Foundation of Hebei Province (No. E2013202247), the Science and Technology Plan Project of Hebei Province (Nos. Z2010112, 10213936), the Hebei Provincial Department of Education Fund (No. 2011128), and the Scientific Research Fund of Hebei Provincial Education (No. QN2014208).

Calibration and combination of monthly near-surface temperature and precipitation predictions over Europe

NASA Astrophysics Data System (ADS)

Rodrigues, Luis R. L.; Doblas-Reyes, Francisco J.; Coelho, Caio A. S.

2018-02-01

A Bayesian method known as the Forecast Assimilation (FA) was used to calibrate and combine monthly near-surface temperature and precipitation outputs from seasonal dynamical forecast systems. The simple multimodel (SMM), a method that combines predictions with equal weights, was used as a benchmark. This research focuses on Europe and adjacent regions for predictions initialized in May and November, covering the boreal summer and winter months. The forecast quality of the FA and SMM as well as the single seasonal dynamical forecast systems was assessed using deterministic and probabilistic measures. A non-parametric bootstrap method was used to account for the sampling uncertainty of the forecast quality measures. We show that the FA performs as well as or better than the SMM in regions where the dynamical forecast systems were able to represent the main modes of climate covariability. An illustration with the near-surface temperature over North Atlantic, the Mediterranean Sea and Middle-East in summer months associated with the well predicted first mode of climate covariability is offered. However, the main modes of climate covariability are not well represented in most situations discussed in this study as the seasonal dynamical forecast systems have limited skill when predicting the European climate. In these situations, the SMM performs better more often.

Design and Fabrication of Multifunctional Sericin Nanoparticles for Tumor Targeting and pH-Responsive Subcellular Delivery of Cancer Chemotherapy Drugs.

PubMed

Huang, Lei; Tao, Kaixiong; Liu, Jia; Qi, Chao; Xu, Luming; Chang, Panpan; Gao, Jinbo; Shuai, Xiaoming; Wang, Guobin; Wang, Zheng; Wang, Lin

2016-03-01

The severe cytotoxicity of cancer chemotherapy drugs limits their clinical applications. Various protein-based nanoparticles with good biocompatibility have been developed for chemotherapy drug delivery in hope of reducing drugs' side effects. Sericin, a natural protein from silk, has no immunogenicity and possesses diverse bioactivities that have prompted sericin's application studies. However, the potential of sericin as a multifunctional nanoscale vehicle for cancer therapy have not been fully explored. Here we report the successful fabrication and characterization of folate-conjugated sericin nanoparticles with cancer-targeting capability for pH-responsive release of doxorubicin (these nanoparticles are termed "FA-SND"). DOX is covalently linked to sericin through pH-sensitive hydrazone bonds that render a pH-triggered release property. The hydrophobicity of DOX and the hydrophilicity of sericin promote the self-assembly of sericin-DOX (SND) nanoconjugates. Folate (FA) is then covalently grafted to SND nanoconjugates as a binding unit for actively targeting cancer cells that overexpress folate receptors. Our characterization study shows that FA-SND nanoparticles exhibit negative surface charges that would reduce nonspecific clearance by circulation. These nanoparticles possess good cytotoxicity and hemocompatibiliy. Acidic environment (pH 5.0) triggers effective DOX release from FA-SND, 5-fold higher than does a neutral condition (pH 7.4). Further, FA-SND nanoparticles specifically target folate-receptor-rich KB cells, and endocytosed into lysosomes, an acidic organelle. The acidic microenvironment of lysosomes promotes a rapid release of DOX to nuclei, producing cancer specific chemo-cytotoxicity. Thus, FA-mediated cancer targeting and lysosomal-acidity promoting DOX release, two sequentially-occurring cellular events triggered by the designed components of FA-SND, form the basis for FA-SND to achieve its localized and intracellular chemo-cytotoxicity. Together, this study suggests that these FA-SND nanoparticles may be a potentially effective carrier particularly useful for delivering hydrophobic chemotherapeutic agents for treating cancers with high-level expression of folate receptors.

Flight Test of the F/A-18 Active Aeroelastic Wing Airplane

NASA Technical Reports Server (NTRS)

Voracek, David

2007-01-01

A viewgraph presentation of flight tests performed on the F/A active aeroelastic wing airplane is shown. The topics include: 1) F/A-18 AAW Airplane; 2) F/A-18 AAW Control Surfaces; 3) Flight Test Background; 4) Roll Control Effectiveness Regions; 5) AAW Design Test Points; 6) AAW Phase I Test Maneuvers; 7) OBES Pitch Doublets; 8) OBES Roll Doublets; 9) AAW Aileron Flexibility; 10) Phase I - Lessons Learned; 11) Control Law Development and Verification & Validation Testing; 12) AAW Phase II RFCS Envelopes; 13) AAW 1-g Phase II Flight Test; 14) Region I - Subsonic 1-g Rolls; 15) Region I - Subsonic 1-g 360 Roll; 16) Region II - Supersonic 1-g Rolls; 17) Region II - Supersonic 1-g 360 Roll; 18) Region III - Subsonic 1-g Rolls; 19) Roll Axis HOS/LOS Comparison Region II - Supersonic (open-loop); 20) Roll Axis HOS/LOS Comparison Region II - Supersonic (closed-loop); 21) AAW Phase II Elevated-g Flight Test; 22) Region I - Subsonic 4-g RPO; and 23) Phase II - Lessons Learned

Near infrared fluorescent trypsin stabilized gold nanoclusters as surface plasmon enhanced energy transfer biosensor and in vivo cancer imaging bioprobe.

PubMed

Liu, Jing-Min; Chen, Jia-Tong; Yan, Xiu-Ping

2013-03-19

The simplicity of the green-synthesized routine and the availability of surface modification of diverse bioactive molecules make noble metal nanostructures highly suitable as multifunctional biomaterials for biological and biomedical application. Here, we report the preparation of trypsin stabilized gold nanoclusters (try-AuNCs) with near-infrared fluorescence for biosensing heparin based on surface plasmon enhanced energy transfer (SPEET) and folic acid (FA) modified try-AuNCs for in vivo cancer bioimaging. The SPEET/try-AuNCs fluorescence biosensor was designed via heparin mediated energy transfer between try-AuNCs and cysteamine modified gold nanoparticles (cyst-AuNPs). The developed SPEET/try-AuNCs fluorescence biosensor allowed sensitive and selective detection of heparin with a linear range of 0.1-4.0 μg mL(-1) and a detection limit (3s) of 0.05 μg mL(-1). The relative standard deviation for eleven replicate detections of 2.5 μg mL(-1) heparin was 1.1%, and the recoveries of the spiked heparin in human serum samples ranged from 97% to 100%. In addition, folic acid was immobilized on the surface of try-AuNCs to ameliorate the specific affinity of AuNCs for tumors, and the near-infrared fluorescent FA-try-AuNCs were applied for in vivo cancer imaging of high folate receptor (FR) expressing Hela tumor. In vivo study of the dynamic behavior and targeting ability of FA-try-AuNCs probe to Hela tumor bearing mice and normal nude mice validated the high specific affinity of FA-try-AuNCs probe to FR positive tumors. The results show that the prepared try-AuNCs have great potential as multifunctional biomaterials for biosensing biomolecules with SPEET mode and in vivo cancer imaging with high targeting ability.

Longitudinal in-vivo diffusion tensor imaging for assessing brain developmental changes in BALB/cJ mice, a model of reduced sociability relevant to autism.

PubMed

Kumar, Manoj; Kim, Sungheon; Pickup, Stephen; Chen, Rong; Fairless, Andrew H; Ittyerah, Ranjit; Abel, Ted; Brodkin, Edward S; Poptani, Harish

2012-05-21

Diffusion tensor imaging (DTI) is highly sensitive in detecting brain structure and connectivity phenotypes in autism spectrum disorders (ASD). Since one of the core symptoms of ASD is reduced sociability (reduced tendency to seek social interaction), we hypothesized that DTI will be sensitive in detecting neural phenotypes that correlate with decreased sociability in mouse models. Relative to C57BL/6J (B6) mice, juvenile BALB/cJ mice show reduced sociability. We performed social approach test in a three-chambered apparatus and in-vivo longitudinal DTI at post-natal days 30, 50 and 70 days-of-age in BALB/cJ (n=32) and B6 (n=15) mice to assess the correlation between DTI and sociability and to evaluate differences in DTI parameters between these two strains. Fractional anisotropy (FA) and mean diffusivity (MD) values from in-vivo DTI data were analyzed from white matter (corpus callosum, internal and external capsule) and gray matter (cerebral cortex, frontal motor cortex, hippocampus, thalamus and amygdaloid) regions based on their relevance to ASD. A moderate but significant (p<0.05) negative correlation between sociability and FA in hippocampus and frontal motor cortex was noted for BALB/cJ mice at 30 days-of-age. Significant differences in FA and MD values between BALB/cJ and B6 mice were observed in most white and gray matter areas at all three time points. Significant differences in developmental trajectories of FA and MD values from thalamus and frontal motor cortex were also observed between BALB/cJ and B6, indicating relative under-connectivity in BALB/cJ mice. These results indicate that DTI may be used as an in-vivo, non-invasive imaging method to assess developmental trajectories of brain connectivity in mouse models of neurodevelopmental and behavioral disorders. Copyright © 2012 Elsevier B.V. All rights reserved.

Longitudinal in-vivo diffusion tensor imaging for assessing brain developmental changes in BALB/cJ mice, a model of reduced sociability relevant to autism

PubMed Central

Kumar, Manoj; Kim, Sungheon; Pickup, Stephen; Chen, Rong; Fairless, Andrew H.; Ittyerah, Ranjit; Abel, Ted; Brodkin, Edward S.; Poptani, Harish

2012-01-01

Diffusion tensor imaging (DTI) is highly sensitive in detecting brain structure and connectivity phenotypes in autism spectrum disorders (ASD). Since one of the core symptoms of ASD is reduced sociability (reduced tendency to seek social interaction), we hypothesized that DTI will be sensitive in detecting neural phenotypes that correlate with decreased sociability in mouse models. Relative to C57BL/6J (B6) mice, juvenile BALB/cJ mice show reduced sociability. We performed social approach test in a three-chambered apparatus and in-vivo longitudinal DTI at post-natal days 30, 50 and 70 days-of-age in BALB/cJ (n=32) and B6 (n=15) mice to assess the correlation between DTI and sociability and to evaluate differences in DTI parameters between these two strains. Fractional anisotropy (FA) and mean diffusivity (MD) values from in-vivo DTI data were analyzed from white matter (corpus callosum, internal and external capsule) and gray matter (cerebral cortex, frontal motor cortex, hippocampus, thalamus and amygdaloid) regions based on their relevance to ASD. A moderate but significant (p<0.05) negative correlation between sociability and FA in hippocampus and frontal motor cortex was noted for BALB/cJ mice at 30 days-of-age. Significant differences in FA and MD values between BALB/cJ and B6 mice were observed in most white and gray matter areas at all three time points. Significant differences in developmental trajectories of FA and MD values from thalamus and frontal motor cortex were also observed between BALB/cJ and B6, indicating relative under-connectivity in BALB/cJ mice. These results indicate that DTI may be used as an in-vivo, non-invasive imaging method to assess developmental trajectories of brain connectivity in mouse models of neurodevelopmental and behavioral disorders. PMID:22513103

Diffusion Tensor Imaging of the Cerebellum and Eyeblink Conditioning in Fetal Alcohol Spectrum Disorder

PubMed Central

Spottiswoode, B.S.; Meintjes, E.M.; Anderson, A.W.; Molteno, C.D.; Stanton, M.E.; Dodge, N.C.; Gore, J.C.; Peterson, B.S.; Jacobson, J.L.; Jacobson, S.W.

2011-01-01

Background Prenatal alcohol exposure is related to a wide range of neurocognitive effects. Eyeblink conditioning (EBC), which involves temporal pairing of a conditioned with an unconditioned stimulus, has been shown to be a potential biomarker of fetal alcohol exposure. A growing body of evidence suggests that white matter may be a specific target of alcohol teratogenesis, and the neural circuitry underlying EBC is known to involve the cerebellar peduncles. Diffusion tensor imaging (DTI) is a magnetic resonance imaging (MRI) technique which has proven useful for assessing central nervous system white matter integrity. This study used DTI to examine the degree to which the fetal alcohol-related deficit in EBC may be mediated by structural impairment in the cerebellar peduncles. Methods 13 children with fetal alcohol spectrum disorder (FASD) and 12 matched controls were scanned using DTI and structural MRI sequences. The DTI data were processed using a voxelwise technique, and the structural data were used for volumetric analyses. Prenatal alcohol exposure group and EBC performance were examined in relation to brain volumes and outputs from the DTI analysis. Results FA and perpendicular diffusivity group differences between alcohol-exposed and nonexposed children were identified in the left middle cerebellar peduncle. Alcohol exposure correlated with lower fractional anisotropy (FA) and greater perpendicular diffusivity in this region, and these correlations remained significant even after controlling for total brain and cerebellar volume. Conversely, trace conditioning performance was related to higher FA and lower perpendicular diffusivity in the left middle peduncle. The effect of prenatal alcohol exposure on trace conditioning was partially mediated by lower FA in this region. Conclusions This study extends recent findings that have used DTI to reveal microstructural deficits in white matter in children with FASD. This is the first DTI study to demonstrate mediation of a fetal alcohol-related effect on neuropsychological function by deficits in white matter integrity. PMID:21790667

Oral manifestations compatible with chronic graft-versus-host disease in patients with Fanconi anemia.

PubMed

Grein Cavalcanti, Laura; Fuentes Araújo, Renata L; Bonfim, Carmem; Torres-Pereira, Cassius C

2015-02-01

Fanconi anemia (FA) is a genetic disease that is characterized by several congenital abnormalities and progressive bone marrow failure and is associated with an increased susceptibility to malignant disorders. Currently, the only potential cure for hematological disorders is hematopoietic stem cell transplantation (HSCT). However, 1 of the most common complications after HSCT is the development of oral chronic graft-versus-host disease (cGVHD), which is also a risk factor for the development of cancer, particularly oral squamous cell carcinoma. Therefore, the purpose of this study was to describe the prevalence and characteristics of oral manifestations compatible with cGVHD in patients diagnosed with FA according to the National Institutes of Health (NIH) consensus criteria. A total of 96 patients (51 females, 45 males; median age, 16 years) with FA, who were in medical follow-up after HSCT at the outpatient clinic of the bone marrow transplantation unit (Hospital de Clínicas from the Universidade Federal do Paraná) underwent an oral evaluation between January 2013 and December 2013. Post-HSCT periods varied from 1 to 261 months and were divided into 3 periods: immediate post-HSCT period; intermediate post-HSC period, and late post-HSCT period. Among the evaluated patients, 40 of 96 (42%) presented with oral manifestations of cGVHD, with 29 of 40 (73%) of these patients in the late post-HSCT period. NIH scale scores varied from 0 to 10, and lichenoid and hyperkeratotic lesions were the abnormalities most frequently observed (100%). Overall, a high prevalence of oral manifestations was observed for cGVHD patients with FA. These data highlight the importance of monitoring oral manifestations compatible with cGVHD to identify and treat individuals with a higher risk of developing oral cancer. Copyright © 2015 American Society for Blood and Marrow Transplantation. Published by Elsevier Inc. All rights reserved.

Radionuclide 131I-labeled multifunctional dendrimers for targeted SPECT imaging and radiotherapy of tumors

NASA Astrophysics Data System (ADS)

Zhu, Jingyi; Zhao, Lingzhou; Cheng, Yongjun; Xiong, Zhijuan; Tang, Yueqin; Shen, Mingwu; Zhao, Jinhua; Shi, Xiangyang

2015-10-01

We report the synthesis, characterization, and utilization of radioactive 131I-labeled multifunctional dendrimers for targeted single-photon emission computed tomography (SPECT) imaging and radiotherapy of tumors. In this study, amine-terminated poly(amidoamine) dendrimers of generation 5 (G5.NH2) were sequentially modified with 3-(4'-hydroxyphenyl)propionic acid-OSu (HPAO) and folic acid (FA) linked with polyethylene glycol (PEG), followed by acetylation modification of the dendrimer remaining surface amines and labeling of radioactive iodine-131 (131I). The generated multifunctional 131I-G5.NHAc-HPAO-PEG-FA dendrimers were characterized via different methods. We show that prior to 131I labeling, the G5.NHAc-HPAO-PEG-FA dendrimers conjugated with approximately 9.4 HPAO moieties per dendrimer are noncytotoxic at a concentration up to 20 μM and are able to target cancer cells overexpressing FA receptors (FAR), thanks to the modified FA ligands. In the presence of a phenol group, radioactive 131I is able to be efficiently labeled onto the dendrimer platform with good stability and high radiochemical purity, and render the platform with an ability for targeted SPECT imaging and radiotherapy of an FAR-overexpressing xenografted tumor model in vivo. The designed strategy to use the facile dendrimer nanotechnology may be extended to develop various radioactive theranostic nanoplatforms for targeted SPECT imaging and radiotherapy of different types of cancer.We report the synthesis, characterization, and utilization of radioactive 131I-labeled multifunctional dendrimers for targeted single-photon emission computed tomography (SPECT) imaging and radiotherapy of tumors. In this study, amine-terminated poly(amidoamine) dendrimers of generation 5 (G5.NH2) were sequentially modified with 3-(4'-hydroxyphenyl)propionic acid-OSu (HPAO) and folic acid (FA) linked with polyethylene glycol (PEG), followed by acetylation modification of the dendrimer remaining surface amines and labeling of radioactive iodine-131 (131I). The generated multifunctional 131I-G5.NHAc-HPAO-PEG-FA dendrimers were characterized via different methods. We show that prior to 131I labeling, the G5.NHAc-HPAO-PEG-FA dendrimers conjugated with approximately 9.4 HPAO moieties per dendrimer are noncytotoxic at a concentration up to 20 μM and are able to target cancer cells overexpressing FA receptors (FAR), thanks to the modified FA ligands. In the presence of a phenol group, radioactive 131I is able to be efficiently labeled onto the dendrimer platform with good stability and high radiochemical purity, and render the platform with an ability for targeted SPECT imaging and radiotherapy of an FAR-overexpressing xenografted tumor model in vivo. The designed strategy to use the facile dendrimer nanotechnology may be extended to develop various radioactive theranostic nanoplatforms for targeted SPECT imaging and radiotherapy of different types of cancer. Electronic supplementary information (ESI) available: Part of the experimental details and additional experimental results. See DOI: 10.1039/c5nr05585g

Fabrication of functional hollow microspheres constructed from MOF shells: Promising drug delivery systems with high loading capacity and targeted transport

PubMed Central

Gao, Xuechuan; Hai, Xiao; Baigude, Huricha; Guan, Weihua; Liu, Zhiliang

2016-01-01

An advanced multifunctional, hollow metal-organic framework (MOF) drug delivery system with a high drug loading level and targeted delivery was designed and fabricated for the first time and applied to inhibit tumour cell growth. This hollow MOF targeting drug delivery system was prepared via a simple post-synthetic surface modification procedure, starting from hollow ZIF-8 successfully obtained for the first time via a mild phase transformation under solvothermal conditions. As a result, the hollow ZIF-8 exhibits a higher loading capacity for the model anticancer drug 5-fluorouracil (5-FU). Subsequently, 5-FU-loaded ZIF-8 was encapsulated into polymer layers (FA-CHI-5-FAM) with three components: a chitosan (CHI) backbone, the imaging agent 5-carboxyfluorescein (5-FAM), and the targeting reagent folic acid (FA). Thus, an advanced drug delivery system, ZIF-8/5-FU@FA-CHI-5-FAM, was fabricated. A cell imaging assay demonstrated that ZIF-8/5-FU@FA-CHI-5-FAM could target and be taken up by MGC-803 cells. Furthermore, the as-prepared ZIF-8/5-FU@FA-CHI-5-FAM exhibited stronger cell growth inhibitory effects on MGC-803 cells because of the release of 5-FU, as confirmed by a cell viability assay. In addition, a drug release experiment in vitro indicated that ZIF-8/5-FU@FA-CHI-5-FAM exhibited high loading capacity (51%) and a sustained drug release behaviour. Therefore, ZIF-8/5-FU@FA-CHI-5-FAM could provide targeted drug transportation, imaging tracking and localized sustained release. PMID:27876876

White Matter Tract Integrity in Alzheimer's Disease vs. Late Onset Bipolar Disorder and Its Correlation with Systemic Inflammation and Oxidative Stress Biomarkers.

PubMed

Besga, Ariadna; Chyzhyk, Darya; Gonzalez-Ortega, Itxaso; Echeveste, Jon; Graña-Lecuona, Marina; Graña, Manuel; Gonzalez-Pinto, Ana

2017-01-01

Background: Late Onset Bipolar Disorder (LOBD) is the development of Bipolar Disorder (BD) at an age above 50 years old. It is often difficult to differentiate from other aging dementias, such as Alzheimer's Disease (AD), because they share cognitive and behavioral impairment symptoms. Objectives: We look for WM tract voxel clusters showing significant differences when comparing of AD vs. LOBD, and its correlations with systemic blood plasma biomarkers (inflammatory, neurotrophic factors, and oxidative stress). Materials: A sample of healthy controls (HC) ( n = 19), AD patients ( n = 35), and LOBD patients ( n = 24) was recruited at the Alava University Hospital. Blood plasma samples were obtained at recruitment time and analyzed to extract the inflammatory, oxidative stress, and neurotrophic factors. Several modalities of MRI were acquired for each subject, Methods: Fractional anisotropy (FA) coefficients are obtained from diffusion weighted imaging (DWI). Tract based spatial statistics (TBSS) finds FA skeleton clusters of WM tract voxels showing significant differences for all possible contrasts between HC, AD, and LOBD. An ANOVA F -test over all contrasts is carried out. Results of F -test are used to mask TBSS detected clusters for the AD > LOBD and LOBD > AD contrast to select the image clusters used for correlation analysis. Finally, Pearson's correlation coefficients between FA values at cluster sites and systemic blood plasma biomarker values are computed. Results: The TBSS contrasts with by ANOVA F -test has identified strongly significant clusters in the forceps minor, inferior longitudinal fasciculus, inferior fronto-occipital fasciculus, and cingulum gyrus. The correlation analysis of these tract clusters found strong negative correlation of AD with the nerve growth factor (NGF) and brain derived neurotrophic factor (BDNF) blood biomarkers. Negative correlation of AD and positive correlation of LOBD with inflammation biomarker IL6 was also found. Conclusion: TBSS voxel clusters tract atlas localizations are consistent with greater behavioral impairment and mood disorders in LOBD than in AD. Correlation analysis confirms that neurotrophic factors (i.e., NGF, BDNF) play a great role in AD while are absent in LOBD pathophysiology. Also, correlation results of IL1 and IL6 suggest stronger inflammatory effects in LOBD than in AD.

Resistance to mitomycin C requires direct interaction between the Fanconi anemia proteins FANCA and FANCG in the nucleus through an arginine-rich domain.

PubMed

Kruyt, F A; Abou-Zahr, F; Mok, H; Youssoufian, H

1999-11-26

Fanconi anemia (FA) is a genetically heterogeneous disorder characterized by bone marrow failure, birth defects, and chromosomal instability. Because FA cells are sensitive to mitomycin C (MMC), FA gene products could be involved in cellular defense mechanisms. The FANCA and FANCG proteins deficient in FA groups A and G interact directly with each other. We have localized the mutual interaction domains of these proteins to amino acids 18-29 of FANCA and to two noncontiguous carboxyl-terminal domains of FANCG encompassing amino acids 400-475 and 585-622. Site-directed mutagenesis of FANCA residues 18-29 revealed a novel arginine-rich interaction domain (RRRAWAELLAG). By alanine mutagenesis, Arg(1), Arg(2), and Leu(8) but not Arg(3), Trp(5), and Glu(7) appeared to be critical for binding to FANCG. Similar immunolocalization for FANCA and FANCG suggested that these proteins interact in vivo. Moreover, targeting of FANCA to the nucleus or the cytoplasm with nuclear localization and nuclear export signals, respectively, showed concordance between the localization patterns of FANCA and FANCG. The complementation function of FANCA was abolished by mutations in its FANCG-binding domain. Conversely, stable expression of FANCA mutants encoding intact FANCG interaction domains induced hypersensitivity to MMC in HeLa cells. These results demonstrate that FANCA-FANCG complexes are required for cellular resistance to MMC. Because the FANCC protein deficient in FA group C works within the cytoplasm, we suggest that FANCC and the FANCA-FANCG complexes suppress MMC cytotoxicity within distinct cellular compartments.

Comparison of 1,5-anhydroglucitol, HbA1c, and fructosamine for detection of diabetes mellitus.

PubMed

Yamanouchi, T; Akanuma, Y; Toyota, T; Kuzuya, T; Kawai, T; Kawazu, S; Yoshioka, S; Kanazawa, Y; Ohta, M; Baba, S

1991-01-01

To evaluate the use of serum 1,5-anhydroglucitol (AG) levels in screening for diabetes mellitus, we compared the sensitivity and specificity of HbA1c, fructosamine (FA), and AG in 1620 randomly selected subjects in 11 institutions throughout Japan. Most individuals were receiving diet and/or drug therapy for diabetes. Subjects were separated into four groups based on World Health Organization criteria: nondiabetic control subjects, subjects with impaired glucose tolerance (IGT), patients with diabetes, and patients with other disorders without IGT. The overlap of AG values between each group was less than that of HbA1c or FA values. AG levels were significantly correlated with fasting plasma glucose (r = -0.627), HbA1c (r = -0.629), and FA (r = -0.590) levels. If we took 14 micrograms/ml as the normal lower limit, AG level was highly specific (93.1%), and a decreased AG level indicated diabetes mellitus (84.2% sensitivity). According to the selectivity index (sensitivity value times specificity value), AG determinations were superior to both HbA1c and FA measurements for diabetes screening. When combinations of these tests were used, only AG and HbA1c together were slightly better than AG alone. Thus, together with other advantages of AG, e.g., its wide variance with relatively fair glycemic control and the negligible influence of the sampling conditions, AG level has more potential than HbA1c or FA level as a screening criterion for diabetes.

BLM promotes the activation of Fanconi Anemia signaling pathway.

PubMed

Panneerselvam, Jayabal; Wang, Hong; Zhang, Jun; Che, Raymond; Yu, Herbert; Fei, Peiwen

2016-05-31

Mutations in the human RecQ helicase, BLM, causes Bloom Syndrome, which is a rare autosomal recessive disorder and characterized by genomic instability and an increased risk of cancer. Fanconi Anemia (FA), resulting from mutations in any of the 19 known FA genes and those yet to be known, is also characterized by chromosomal instability and a high incidence of cancer. BLM helicase and FA proteins, therefore, may work in a common tumor-suppressor signaling pathway. To date, it remains largely unclear as to how BLM and FA proteins work concurrently in the maintenance of genome stability. Here we report that BLM is involved in the early activation of FA group D2 protein (FANCD2). We found that FANCD2 activation is substantially delayed and attenuated in crosslinking agent-treated cells harboring deficient Blm compared to similarly treated control cells with sufficient BLM. We also identified that the domain VI of BLM plays an essential role in promoting FANCD2 activation in cells treated with DNA crosslinking agents, especially ultraviolet B. The similar biological effects performed by ΔVI-BLM and inactivated FANCD2 further confirm the relationship between BLM and FANCD2. Mutations within the domain VI of BLM detected in human cancer samples demonstrate the functional importance of this domain, suggesting human tumorigenicity resulting from mtBLM may be at least partly attributed to mitigated FANCD2 activation. Collectively, our data show a previously unknown regulatory liaison in advancing our understanding of how the cancer susceptibility gene products act in concert to maintain genome stability.

Crystal structure of a Fanconi anemia-associated nuclease homolog bound to 5' flap DNA: basis of interstrand cross-link repair by FAN1

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

Gwon, Gwang Hyeon; Kim, Youngran; Liu, Yaqi

2014-10-15

Fanconi anemia (FA) is an autosomal recessive genetic disorder caused by defects in any of 15 FA genes responsible for processing DNA interstrand cross-links (ICLs). The ultimate outcome of the FA pathway is resolution of cross-links, which requires structure-selective nucleases. FA-associated nuclease 1 (FAN1) is believed to be recruited to lesions by a monoubiquitinated FANCI–FANCD2 (ID) complex and participates in ICL repair. Here, we determined the crystal structure of Pseudomonas aeruginosa FAN1 (PaFAN1) lacking the UBZ (ubiquitin-binding zinc) domain in complex with 5' flap DNA. All four domains of the right-hand-shaped PaFAN1 are involved in DNA recognition, with each domainmore » playing a specific role in bending DNA at the nick. The six-helix bundle that binds the junction connects to the catalytic viral replication and repair (VRR) nuclease (VRR nuc) domain, enabling FAN1 to incise the scissile phosphate a few bases distant from the junction. The six-helix bundle also inhibits the cleavage of intact Holliday junctions. PaFAN1 shares several conserved features with other flap structure-selective nucleases despite structural differences. A clamping motion of the domains around the wedge helix, which acts as a pivot, facilitates nucleolytic cleavage. The PaFAN1 structure provides insights into how archaeal Holliday junction resolvases evolved to incise 5' flap substrates and how FAN1 integrates with the FA complex to participate in ICL repair.« less

Agreement between Descriptive and Experimental Analyses of Behavior under Naturalistic Test Conditions

ERIC Educational Resources Information Center

Martens, Brian K.; Gertz, Lynne E.; Werder, Candace Susan de Lacy; Rymanowski, Jennifer L.

2010-01-01

We compared the results of a contingency space analysis (CSA) of behavior-consequence recordings to the results of functional analysis (FA) test conditions involving antecedent stimuli and verbal statements that both differed from and mimicked those in the natural environment. Three preschool children with autism spectrum disorder participated.…

Diffusion-weighted MRI measures suggest increased white-matter integrity in Internet gaming disorder: Evidence from the comparison with recreational Internet game users.

PubMed

Dong, Guangheng; Wu, Lingdan; Wang, Ziliang; Wang, Yifan; Du, Xiaoxia; Potenza, Marc N

2018-06-01

Several studies have suggested that Internet gaming disorder (IGD) is related to altered brain white matter integrity. However, seeming inconsistencies exist and may reflect comparison groups not matched well for certain gaming characteristics. In order to address this possible concern, we recruited in the present study individuals with recreational Internet game use (RGU) comprised of individuals who spend similar amounts of time as IGD subjects playing online games without developing IGD. Diffusion tensor imaging data were collected from 42 IGD and 44 RGU subjects. Whole-brain comparisons showed that IGD subjects demonstrated increased fractional anisotropy (FA) in the bilateral anterior thalamic radiation, anterior limb of the internal capsule, bilateral corticospinal tract, bilateral inferior fronto-occipital fasciculus, corpus callosum, and bilateral inferior longitudinal fasciculus. In addition, Internet-addiction severity was positively correlated with FA values. Taken together, we conclude that IGD is associated with measures of increased white-matter integrity in tracts linking reward circuitry and sensory and motor control systems. Copyright © 2018 Elsevier Ltd. All rights reserved.

VOCs Air Pollutant Cleaning with Polyacrylonitrile/Fly Ash Nanocomposite Electrospun Nanofibrous Membranes

NASA Astrophysics Data System (ADS)

Cong Ge, Jun; Wang, Zi Jian; Kim, Min Soo; Choi, Nag Jung

2018-01-01

Volatile organic compounds (VOCs) as an environmental pollution, which have many kinds of chemical structures, and many of them are very toxic. Therefore, controlling and reducing the presence of VOCs has become a hot topic among researchers for many years. In this study, the VOCs adsorption capacity of polyacrylonitrile/fly ash (PAN/FA) nanocomposite electrospun nanofibrous membranes were investigated. The results indicated that the PAN with different contents of FA powder (20%, 40%, 60%, 80%, and 100% compared with PAN by weight) could be spun well by electrospinning. The diameter of the fiber was very fine and its arrangement was irregular. The PAN nanofibrous membrane containing 60 wt% FA powder had the highest VOCs absorption capacity compared with other nanofibrous membranes due to its large specific surface area.

Analysis of the Three-Dimensional Vector FAÇADE Model Created from Photogrammetric Data

NASA Astrophysics Data System (ADS)

Kamnev, I. S.; Seredovich, V. A.

2017-12-01

The results of the accuracy assessment analysis for creation of a three-dimensional vector model of building façade are described. In the framework of the analysis, analytical comparison of three-dimensional vector façade models created by photogrammetric and terrestrial laser scanning data has been done. The three-dimensional model built from TLS point clouds was taken as the reference one. In the course of the experiment, the three-dimensional model to be analyzed was superimposed on the reference one, the coordinates were measured and deviations between the same model points were determined. The accuracy estimation of the three-dimensional model obtained by using non-metric digital camera images was carried out. Identified façade surface areas with the maximum deviations were revealed.

Disease-Related Microstructural Differences in the Brain in Women With Provoked Vestibulodynia.

PubMed

Gupta, Arpana; Woodworth, Davis C; Ellingson, Benjamin M; Rapkin, Andrea J; Naliboff, Bruce; Kilpatrick, Lisa A; Stains, Jean; Masghati, Salome; Tillisch, Kirsten; Mayer, Emeran A; Labus, Jennifer S

2018-05-01

Provoked vestibulodynia (PVD) is a chronic pelvic pain disorder affecting 16% of the female population. Neuroimaging studies have highlighted central abnormalities in PVD, similar to other chronic pelvic pain disorders, including brain regions involved in sensory processing and modulation of pain. The aim of the study was to determine alterations in the subvoxel, microstructural organization within tissues in PVD compared with healthy control participants (HCs) and a disease control group (irritable bowel syndrome [IBS]). Diffusion tensor imaging magnetic resonance imaging was conducted in 87 age-matched premenopausal women (29 PVD, 29 HCs, 29 IBS). Statistical parameter mapping of fractional anisotropy (FA) and mean diffusivity (MD) maps were used to identify microstructural difference in the brain specific to PVD or shared with IBS. PVD alterations in microstructural organization of the brain were predominantly observed in fibers associated with sensorimotor integration and pain processing that relay information between the thalamus, basal ganglia, sensorimotor, and insular cortex. PVD, compared with HCs, showed extensive increases in the FA of somatosensory and basal ganglia regions. In contrast, PVD and IBS subjects did not show any FA-related group differences. PVD subjects showed greater MD in the basal ganglia compared with HCs (higher MD in the internal capsule and pallidum) and IBS (higher MD in the putamen and pallidum). Increases in MD were associated with increased vaginal muscle tenderness and vulvar pain. The current findings highlight possible shared mechanisms between 2 different pelvic pain disorders, but also highlight the widespread alterations observed specifically in PVD compared with HCs. Alterations in microstructure in PVD were observed in fibers associated with sensorimotor integration and pain processing, which were also associated with increased vaginal muscle tenderness and vulvar pain. These alterations may be contributing to increased pain sensitivity and tenderness, highlighting the need for new therapies targeting the central nervous system. Copyright © 2018 The American Pain Society. Published by Elsevier Inc. All rights reserved.

Comparison of Three Methods for Generating Superhydrophobic, Superoleophobic Nylon Nonwoven Surfaces (Postprint)

DTIC Science & Technology

2011-04-01

AFRL-RX-TY-TP-2010-0076 COMPARISON OF THREE METHODS FOR GENERATING SUPERHYDROPHOBIC , SUPEROLEOPHOBIC NYLON NONWOVEN SURFACES Rahul Saraf...Generating Superhydrophobic , Superoleophobic Nylon Nonwoven Surfaces (POSTPRINT) FA8650-07-1-5916 0602102F GOVT L0 QL102006 ^Saraf, Rahul,; ^Lee, Hoon...Document contains color images. This research deals with creating a superhydrophobic /superoleophobic surface by preparing a metastable Cassie

Evaluation of Fanconi anaemia genes FANCA, FANCC and FANCL in cervical cancer susceptibility.

PubMed

Juko-Pecirep, Ivana; Ivansson, Emma L; Gyllensten, Ulf B

2011-08-01

Disrupting the function of any of the 13 Fanconi anaemia (FA) genes causes a DNA repair deficiency disorder, with patients being susceptible to a number of cancer types. Variation in the family of FA genes has been suggested to affect risk of cervical cancer. The current study evaluates the influence of three genes in the FA pathway on cervical cancer risk in Swedish women. TagSNPs in FANCA, FANCC and FANCL were selected using the Tagger algorithm in Haploview. A total of 81 tagSNPs were genotyped in 782 cases (CIN3 or ICC) and 775 controls using the Illumina GoldenGate Assay and statistically analyzed for association with cervical cancer. 72 SNPs were successfully genotyped in >98% of the samples. Nominal associations were detected for FANCA rs11649196 (p=0.05) and rs4128763 in FANCC (p=0.02). The associations did not withstand correction for multiple testing. The current study does not support that genetic variation in FANCA, FANCC or FANCL genes affects susceptibility to cervical cancer in the Swedish population. Copyright © 2011 Elsevier Inc. All rights reserved.

Architecture and DNA Recognition Elements of the Fanconi Anemia FANCM-FAAP24 Complex

PubMed Central

Coulthard, Rachel; Deans, Andrew J.; Swuec, Paolo; Bowles, Maureen; Costa, Alessandro; West, Stephen C.; McDonald, Neil Q.

2013-01-01

Summary Fanconi anemia (FA) is a disorder associated with a failure in DNA repair. FANCM (defective in FA complementation group M) and its partner FAAP24 target other FA proteins to sites of DNA damage. FANCM-FAAP24 is related to XPF/MUS81 endonucleases but lacks endonucleolytic activity. We report a structure of an FANCM C-terminal fragment (FANCMCTD) bound to FAAP24 and DNA. This S-shaped structure reveals the FANCM (HhH)2 domain is buried, whereas the FAAP24 (HhH)2 domain engages DNA. We identify a second DNA contact and a metal center within the FANCM pseudo-nuclease domain and demonstrate that mutations in either region impair double-stranded DNA binding in vitro and FANCM-FAAP24 function in vivo. We show the FANCM translocase domain lies in proximity to FANCMCTD by electron microscopy and that binding fork DNA structures stimulate its ATPase activity. This suggests a tracking model for FANCM-FAAP24 until an encounter with a stalled replication fork triggers ATPase-mediated fork remodeling. PMID:23932590

Increased left hemisphere impairment in high-functioning autism: a tract based spatial statistics study.

PubMed

Perkins, Thomas John; Stokes, Mark Andrew; McGillivray, Jane Anne; Mussap, Alexander Julien; Cox, Ivanna Anne; Maller, Jerome Joseph; Bittar, Richard Garth

2014-11-30

There is evidence emerging from Diffusion Tensor Imaging (DTI) research that autism spectrum disorders (ASD) are associated with greater impairment in the left hemisphere. Although this has been quantified with volumetric region of interest analyses, it has yet to be tested with white matter integrity analysis. In the present study, tract based spatial statistics was used to contrast white matter integrity of 12 participants with high-functioning autism or Aspergers syndrome (HFA/AS) with 12 typically developing individuals. Fractional Anisotropy (FA) was examined, in addition to axial, radial and mean diffusivity (AD, RD and MD). In the left hemisphere, participants with HFA/AS demonstrated significantly reduced FA in predominantly thalamic and fronto-parietal pathways and increased RD. Symmetry analyses confirmed that in the HFA/AS group, WM disturbance was significantly greater in the left compared to right hemisphere. These findings contribute to a growing body of literature suggestive of reduced FA in ASD, and provide preliminary evidence for RD impairments in the left hemisphere. Copyright © 2014 Elsevier Ireland Ltd. All rights reserved.

Human FAN1 promotes strand incision in 5'-flapped DNA complexed with RPA.

PubMed

Takahashi, Daisuke; Sato, Koichi; Hirayama, Emiko; Takata, Minoru; Kurumizaka, Hitoshi

2015-09-01

Fanconi anaemia (FA) is a human infantile recessive disorder. Seventeen FA causal proteins cooperatively function in the DNA interstrand crosslink (ICL) repair pathway. Dual DNA strand incisions around the crosslink are critical steps in ICL repair. FA-associated nuclease 1 (FAN1) is a DNA structure-specific endonuclease that is considered to be involved in DNA incision at the stalled replication fork. Replication protein A (RPA) rapidly assembles on the single-stranded DNA region of the stalled fork. However, the effect of RPA on the FAN1-mediated DNA incision has not been determined. In this study, we purified human FAN1, as a bacterially expressed recombinant protein. FAN1 exhibited robust endonuclease activity with 5'-flapped DNA, which is formed at the stalled replication fork. We found that FAN1 efficiently promoted DNA incision at the proper site of RPA-coated 5'-flapped DNA. Therefore, FAN1 possesses the ability to promote the ICL repair of 5'-flapped DNA covered by RPA. © The Authors 2015. Published by Oxford University Press on behalf of the Japanese Biochemical Society. All rights reserved.

Rational design of cancer-targeted selenium nanoparticles to antagonize multidrug resistance in cancer cells.

PubMed

Liu, Ting; Zeng, Lilan; Jiang, Wenting; Fu, Yuanting; Zheng, Wenjie; Chen, Tianfeng

2015-05-01

Multidrug resistance is one of the greatest challenges in cancer therapy. Herein we described the synthesis of folate (FA)-conjugated selenium nanoparticles (SeNPs) as cancer-targeted nano-drug delivery system for ruthenium polypyridyl (RuPOP) exhibits strong fluorescence, which allows the direct imaging of the cellular trafficking of the nanosystem. This nanosystem could effectively antagonize against multidrug resistance in liver cancer. FA surface conjugation significantly enhanced the cellular uptake of SeNPs by FA receptor-mediated endocytosis through nystain-dependent lipid raft-mediated and clathrin-mediated pathways. The nanomaterials overcame the multidrug resistance in R-HepG2 cells through inhibition of ABC family proteins expression. Internalized nanoparticles triggered ROS overproduction and induced apoptosis by activating p53 and MAPKs pathways. Moreover, FA-SeNPs exhibited low in vivo acute toxicity, which verified the safety and application potential of FA-SeNPs as nanodrugs. This study provides an effective strategy for the design of cancer-targeted nanodrugs against multidrug resistant cancers. In the combat against hepatocellular carcinoma, multidrug resistance remains one of the obstacles to be overcome. The authors designed and synthesized folate (FA)-conjugated selenium nanoparticles (SeNPs) with enhanced cancer-targeting capability. This system carried ruthenium polypyridyl (RuPOP), an efficient metal-based anti-cancer drug with strong fluorescence. It was shown that this combination was effective in antagonizing against multidrug resistance in vitro. Copyright © 2015 Elsevier Inc. All rights reserved.

Poly(l-lysine)-graft-folic acid-coupled poly(2-methyl-2-oxazoline) (PLL-g-PMOXA-c-FA): a bioactive copolymer for specific targeting to folate receptor-positive cancer cells.

PubMed

Chen, Yin; Cao, Wenbin; Zhou, Junli; Pidhatika, Bidhari; Xiong, Bin; Huang, Lu; Tian, Qian; Shu, Yiwei; Wen, Weijia; Hsing, I-Ming; Wu, Hongkai

2015-02-04

In this study, we present the preparation, characterization and application of a novel bioactive copolymer poly(l-lysine)-graft-folic acid-coupled poly(2-methyl-2-oxazoline) (PLL-g-PMOXA-c-FA), which has a specific interaction with folate receptor (FR)-positive cancer cells. Glass surface immobilized with PLL-g-PMOXA-c-FA was demonstrated to be adhesive to FR-positive cancer cells (HeLa, JEG-3) while nonadhesive to FR-negative ones (MCF-7, HepG2) in 3 h. The specific interaction between conjugated FA on the substrate and FRs on the cells could hardly be inhibited unless a high concentration (5 mM) of free FA was used due to the multivalent nature of it. The FA functionality ratio of the copolymer on the substrate had a significant influence on the adhesion of HeLa cells, and our experiments revealed that the affinity of the substrate to the cells declined dramatically with the decrease of functionality ratio. This was believed to be caused by the polydispersity of PMOXA tethers, as supported by GPC and ToF-SIMS data. As a proof of concept in the application of our material, we demonstrated successful recovery of HeLa cells from mixture with MCF-7 (1:100) on the copolymer-coated glass, and our results showed that both high sensitivity (95.6 ± 13.3%) and specificity (24.3 ± 8.6%) were achieved.

Impact of natural organic matter on arsenic removal by modified granular natural siderite: Evidence of ternary complex formation by HPSEC-UV-ICP-MS.

PubMed

Li, Fulan; Guo, Huaming; Zhou, Xiaoqian; Zhao, Kai; Shen, Jiaxing; Liu, Fei; Wei, Chao

2017-02-01

High arsenic (As) groundwater usually has high concentrations of natural organic matter (NOM). Effects of NOM on arsenic adsorption were investigated to evaluate the efficiency of modified granular natural siderite (MGNS) as an adsorbent for groundwater arsenic remediation. Humic and fulvic acids (HA/FA) were selected as model NOM compounds. In batch tests, HA or FA was either first adsorbed onto the MGNS, or applied together with dissolved arsenic to investigate effects of both adsorbed and dissolved NOM on arsenic removal. The kinetic data showed no significant effects of both adsorbed and dissolved HA/FA on As(III) adsorption. However, As(V) removal was inhibited, whereby the adsorbed NOM compounds had greater inhibitory effect. The inhibitory effect on As(V) removal increased with increasing NOM concentrations. FA exhibited higher inhibitory effect than HA at the same concentration. Steric Exclusion Chromatography-HPLC (SEC-HPLC), and High-Performance Size Exclusion Chromatography-UV-Inductively Coupled Plasma Mass Spectrometry (HPSEC-UV-ICP-MS) revealed that As(V) removal was mostly achieved by the oxyanion adsorption and adversely affected by dissolved FA via competitive adsorption for surface sites. In addition to oxyanion adsorption, removal of As(V) was related to scavenging of ternary HA-As-Fe complexes, which led to the less inhibitory effect of dissolved HA on As(V) removal than dissolved FA via competitive adsorption. Copyright © 2016 Elsevier Ltd. All rights reserved.

Modification of nitrifying biofilm into nitritating one by combination of increased free ammonia concentrations, lowered HRT and dissolved oxygen concentration.

PubMed

Zekker, Ivar; Rikmann, Ergo; Tenno, Toomas; Menert, Anne; Lemmiksoo, Vallo; Saluste, Alar; Tenno, Taavo; Tomingas, Martin

2011-01-01

Nitrifying biomass on ring-shaped carriers was modified to nitritating one in a relatively short period of time (37 days) by limiting the air supply, changing the aeration regime, shortening the hydraulic retention time and increasing free ammonia (FA) concentration in the moving-bed biofilm reactor (MBBR). The most efficient strategy for the development and maintenance of nitritating biofilm was found to be the inhibition of nitrifying activity by higher FA concentrations (up to 6.5 mg/L) in the process. Reject water from sludge treatment from the Tallinn Wastewater Treatment Plant was used as substrate in the MBBR. The performance of high-surfaced biocarriers taken from the nitritating activity MBBR was further studied in batch tests to investigate nitritation and nitrification kinetics with various FA concentrations and temperatures. The maximum nitrite accumulation ratio (96.6%) expressed as the percentage of NO2(-)-N/NOx(-)-N was achieved for FA concentration of 70 mg/L at 36 degrees C. Under the same conditions the specific nitrite oxidation rate achieved was 30 times lower than the specific nitrite formation rate. It was demonstrated that in the biofilm system, inhibition by FA combined with the optimization of the main control parameters is a good strategy to achieve nitritating activity and suppress nitrification.

Formulation of unidirectional release buccal patches of carbamazepine and study of permeation through porcine buccal mucosa

PubMed Central

Govindasamy, Parthasarathy; Kesavan, Bhaskar Reddy; Narasimha, Jayaveera Korlakunta

2013-01-01

Objective To achieve transbuccal release of carbamazepine by loading in unidirectional release mucoadhesive buccal patches. Methods Buccal patches of carbamazepine with unidirectional drug release were prepared using hydroxypropyl methyl cellulose, polyvinyl alcohol, polyvinyl pyrrolidone and ethyl cellulose by solvent casting method. Water impermeable backing layer (Pidilite® Biaxially-oriented polypropylene film) of patches provided unidirectional drug release. They were evaluated for thickness, mass uniformity, surface pH and folding endurance. Six formulations FA2, FA8, FA10, FB1, FB14 and FB16 (folding endurance above 250) were evaluated further for swelling studies, ex vivo mucoadhesive strength, ex vivo mucoadhesion time, in vitro drug release, ex vivo permeation, accelerated stability studies and FTIR and XRD spectral studies. Results The ex vivo mucoadhesion time of patches ranged between 109 min (FA10) to 126 min (FB14). The ex vivo mucoadhesive force was in the range of 0.278 to 0.479 kg/m/s. The in vitro drug release studies revealed that formulation FA8 released 84% and FB16 released 99.01% of drug in 140 min. Conclusions The prepared unidirectional buccal patches of carbamazepine provided a maximum drug release within specified mucoadhesion period and it indicates a potential alternative drug delivery system for systemic delivery of carbamazepine. PMID:24093793

Dual tumor-targeted poly(lactic-co-glycolic acid)–polyethylene glycol–folic acid nanoparticles: a novel biodegradable nanocarrier for secure and efficient antitumor drug delivery

PubMed Central

Chen, Jia; Wu, Qi; Luo, Li; Wang, Yi; Zhong, Yuan; Dai, Han-Bin; Sun, Da; Luo, Mao-Ling; Wu, Wei; Wang, Gui-Xue

2017-01-01

Further specific target-ability development of biodegradable nanocarriers is extremely important to promote their security and efficiency in antitumor drug-delivery applications. In this study, a facilely prepared poly(lactic-co-glycolic acid) (PLGA)–polyethylene glycol (PEG)–folic acid (FA) copolymer was able to self-assemble into nanoparticles with favorable hydrodynamic diameters of around 100 nm and negative surface charge in aqueous solution, which was expected to enhance intracellular antitumor drug delivery by advanced dual tumor-target effects, ie, enhanced permeability and retention induced the passive target, and FA mediated the positive target. Fluorescence-activated cell-sorting and confocal laser-scanning microscopy results confirmed that doxorubicin (model drug) loaded into PLGA-PEG-FA nanoparticles was able to be delivered efficiently into tumor cells and accumulated at nuclei. In addition, all hemolysis, 3-(4,5-dimethylthiazol-2-yl)-5-(3-carboxymethoxyphenyl)-2-(4-sulfophenyl)-2H-tetrazolium, and zebrafish-development experiments demonstrated that PLGA-PEG-FA nanoparticles were biocompatible and secure for biomedical applications, even at high polymer concentration (0.1 mg/mL), both in vitro and in vivo. Therefore, PLGA-PEG-FA nanoparticles provide a feasible controlled-release platform for secure and efficient antitumor drug delivery. PMID:28848351

Ultra-high field diffusion tensor imaging of articular cartilage correlated with histology and scanning electron microscopy.

PubMed

Raya, José G; Arnoldi, Andreas P; Weber, Daniel L; Filidoro, Lucianna; Dietrich, Olaf; Adam-Neumair, Silvia; Mützel, Elisabeth; Melkus, Gerd; Putz, Reinhard; Reiser, Maximilian F; Jakob, Peter M; Glaser, Christian

2011-08-01

To investigate the relationship of the different diffusion tensor imaging (DTI) parameters (ADC, FA, and first eigenvector (EV)) to the constituents (proteoglycans and collagen), the zonal arrangement of the collagen network, and mechanical loading of articular cartilage. DTI of eight cartilage-on-bone samples of healthy human patellar cartilage was performed at 17.6 T. Three samples were additionally imaged under indentation loading. After DTI, samples underwent biomechanical testing, safranin-O staining for semiquantitative proteoglycan estimation, and scanning electron microscopy (SEM) for depicting collagen architecture. From the articular surface to the bone-cartilage interface, ADC continuously decreased and FA increased. Cartilage zonal heights calculated from EVs strongly correlated with SEM-derived zonal heights (P < 0.01, r (2)=0.87). Compression reduced ADC in the superficial 30% of cartilage and increased FA in the superficial 5% of cartilage. Reorientation of the EVs indicative of collagen fiber reorientation under the indenter was observed. No significant correlation was found between ADC, FA, and compressive stiffness. Correlating ADC and FA with proteoglycan and collagen content suggests that diffusion is dominated by different depth-dependent mechanisms within cartilage. Knowledge of the spatial distribution of the DTI parameters and their variation contributes to form a database for future analysis of defective cartilage.

Assessment of the structural brain network reveals altered connectivity in children with unilateral cerebral palsy due to periventricular white matter lesions.

PubMed

Pannek, Kerstin; Boyd, Roslyn N; Fiori, Simona; Guzzetta, Andrea; Rose, Stephen E

2014-01-01

Cerebral palsy (CP) is a term to describe the spectrum of disorders of impaired motor and sensory function caused by a brain lesion occurring early during development. Diffusion MRI and tractography have been shown to be useful in the study of white matter (WM) microstructure in tracts likely to be impacted by the static brain lesion. The purpose of this study was to identify WM pathways with altered connectivity in children with unilateral CP caused by periventricular white matter lesions using a whole-brain connectivity approach. Data of 50 children with unilateral CP caused by periventricular white matter lesions (5-17 years; manual ability classification system [MACS] I = 25/II = 25) and 17 children with typical development (CTD; 7-16 years) were analysed. Structural and High Angular Resolution Diffusion weighted Images (HARDI; 64 directions, b = 3000 s/mm(2)) were acquired at 3 T. Connectomes were calculated using whole-brain probabilistic tractography in combination with structural parcellation of the cortex and subcortical structures. Connections with altered fractional anisotropy (FA) in children with unilateral CP compared to CTD were identified using network-based statistics (NBS). The relationship between FA and performance of the impaired hand in bimanual tasks (Assisting Hand Assessment-AHA) was assessed in connections that showed significant differences in FA compared to CTD. FA was reduced in children with unilateral CP compared to CTD. Seven pathways, including the corticospinal, thalamocortical, and fronto-parietal association pathways were identified simultaneously in children with left and right unilateral CP. There was a positive relationship between performance of the impaired hand in bimanual tasks and FA within the cortico-spinal and thalamo-cortical pathways (r(2) = 0.16-0.44; p < 0.05). This study shows that network-based analysis of structural connectivity can identify alterations in FA in unilateral CP, and that these alterations in FA are related to clinical function. Application of this connectome-based analysis to investigate alterations in connectivity following treatment may elucidate the neurological correlates of improved functioning due to intervention.

Photocatalytic reduction of nitrate using titanium dioxide for regeneration of ion exchange brine

PubMed Central

Yang, Ting; Doudrick, Kyle; Westerhoff, Paul

2016-01-01

Nitrate is often removed from groundwater by ion exchange (IX) before its use as drinking water. Accumulation of nitrate in IX brine reduces the efficiency of IX regeneration and the useful life of the regeneration brine. For the first time, we present a strategy to photocatalytically reduce nitrate in IX brine, thereby extending the use of the brine. Titanium dioxide (Evonik P90), acting as photocatalyst, reduced nitrate effectively in both synthetic brines and sulfate-removed IX brine when formic acid (FA) was used as the hole scavenger (i.e., electron donor) and the initial FA to nitrate molar ratio (IFNR) was 5.6. Increasing the NaCl level in the synthetic brine slowed the nitrate reduction rate without affecting byproduct selectivity of ammonium and gaseous N species (e.g., N2, N2O). In a non-modified IX brine, nitrate removal was greatly inhibited owing to the presence of sulfate, which competed with nitrate for active surface sites on P90 and induced aggregation of P90 nanoparticles. After removing sulfate through barium sulfate precipitation, nitrate was effectively reduced; approximately 3.6 × 1024 photons were required to reduce each mole of nitrate to 83% N Gases and 17% NH4+. To make optimum use of FA and control the residual FA level in treated brine, the IFNR was varied. High IFNRs (e.g., 4, 5.6) were found to be more efficient for nitrate reduction but left higher residual FA in brine. IX column tests were performed to investigate the impact of residual FA for brine reuse. The residual FA in the brine did not significantly affect the nitrate removal capacity of IX resins, and formate contamination of treated water could be eliminated by rinsing with one bed volume of fresh brine. PMID:23276425

A case report of Fanconi anemia diagnosed by genetic testing followed by prenatal diagnosis.

PubMed

Lee, Hwa Jeen; Park, Seungman; Kang, Hyoung Jin; Jun, Jong Kwan; Lee, Jung Ae; Lee, Dong Soon; Park, Sung Sup; Seong, Moon-Woo

2012-09-01

Fanconi anemia (FA) is a rare genetic disorder affecting multiple body systems. Genetic testing, including prenatal testing, is a prerequisite for the diagnosis of many clinical conditions. However, genetic testing is complicated for FA because there are often many genes that are associated with its development, and large deletions, duplications, or sequence variations are frequently found in some of these genes. This study describes successful genetic testing for molecular diagnosis, and subsequent prenatal diagnosis, of FA in a patient and his family in Korea. We analyzed all exons and flanking regions of the FANCA, FANCC, and FANCG genes for mutation identification and subsequent prenatal diagnosis. Multiplex ligation-dependent probe amplification analysis was performed to detect large deletions or duplications in the FANCA gene. Molecular analysis revealed two mutations in the FANCA gene: a frameshift mutation c.2546delC and a novel splice-site mutation c.3627-1G>A. The FANCA mutations were separately inherited from each parent, c.2546delC was derived from the father, whereas c.3627-1G>A originated from the mother. The amniotic fluid cells were c.3627-1G>A heterozygotes, suggesting that the fetus was unaffected. This is the first report of genetic testing that was successfully applied to molecular diagnosis of a patient and subsequent prenatal diagnosis of FA in a family in Korea.

A narrative synthesis of the applicability of the CaR-FA-X model in child and adolescent populations: a systematic review.

PubMed

Stewart, Tracy M; Hunter, Simon C; Rhodes, Sinéad M

2017-10-01

The CaR-FA-X model [Williams, J. M. G., Barnhofer, T., Crane, C., Hermans, D., Raes, F., Watkins, E., … Dalgleish, T. (2007). Autobiographical memory specificity and emotional disorder. Psychological Bulletin, 133(1), 122-148. doi: 10.1037/0033-2909.133.1.122 ] is the most prominent and comprehensive model of overgeneral autobiographical memory (OGM) and provides a framework for OGM. The model comprises of three mechanisms, capture and rumination, functional avoidance and impaired executive control. These can independently, or in interaction, account for OGM. This systematic review aims to evaluate the existing research on the CaR-FA-X model, and trauma exposure studies specific to child and adolescent populations. The following databases were searched: "PsychInfo", "PsychArticles", "PubMed", "Web of Science", "Medline", "SCOPUS" and "Embase" for English-language, peer-reviewed papers with samples

Neuropsychiatry and White Matter Microstructure in Huntington's Disease.

PubMed

Gregory, Sarah; Scahill, Rachael I; Seunarine, Kiran K; Stopford, Cheryl; Zhang, Hui; Zhang, Jiaying; Orth, Michael; Durr, Alexandra; Roos, Raymund A C; Langbehn, Douglas R; Long, Jeffrey D; Johnson, Hans; Rees, Geraint; Tabrizi, Sarah J; Craufurd, David

2015-01-01

Neuropsychiatric symptoms in Huntington's disease (HD) are often evident prior to clinical diagnosis. Apathy is highly correlated with disease progression, while depression and irritability occur at different stages of the disease, both before and after clinical onset. Little is understood about the neural bases of these neuropsychiatric symptoms and to what extent those neural bases are analogous to neuropsychiatric disorders in the general population. We used Diffusion Tensor Imaging (DTI) to investigate structural connectivity between brain regions and any putative microstructural changes associated with depression, apathy and irritability in HD. DTI data were collected from 39 premanifest and 45 early-HD participants in the Track-HD study and analysed using whole-brain Tract-Based Spatial Statistics. We used regression analyses to identify white matter tracts whose structural integrity (as measured by fractional anisotropy, FA) was correlated with HADS-depression, PBA-apathy or PBA-irritability scores in gene-carriers and related to cumulative probability to onset (CPO). For those with the highest CPO, we found significant correlations between depression scores and reduced FA in the splenium of the corpus callosum. In contrast, those with lowest CPO demonstrated significant correlations between irritability scores and widespread FA reductions. There was no significant relationship between apathy and FA throughout the whole brain. We demonstrate that white matter changes associated with both depression and irritability in HD occur at different stages of disease progression concomitant with their clinical presentation.

Complement-fixing activity of fulvic acid from Shilajit and other natural sources.

PubMed

Schepetkin, Igor A; Xie, Gang; Jutila, Mark A; Quinn, Mark T

2009-03-01

Shilajit has been used traditionally in folk medicine for the treatment of a variety of disorders, including syndromes involving excessive complement activation. Extracts of Shilajit contain significant amounts of fulvic acid (FA), and it has been suggested that FA is responsible for many therapeutic properties of Shilajit. However, little is known regarding the physical and chemical properties of Shilajit extracts, and nothing is known about their effects on the complement system. To address this issue, extracts of commercial Shilajit were fractionated using anion exchange and size-exclusion chromatography. One neutral (S-I) and two acidic (S-II and S-III) fractions were isolated, characterized and compared with standardized FA samples. The most abundant fraction (S-II) was further fractionated into three sub-fractions (S-II-1 to S-II-3). The van Krevelen diagram showed that the Shilajit fractions are the products of polysaccharide degradation, and all fractions, except S-II-3, contained type II arabinogalactan. All Shilajit fractions exhibited dose-dependent complement-fixing activity in vitro with high potency. Furthermore, a strong correlation was found between the complement-fixing activity and carboxylic group content in the Shilajit fractions and other FA sources. These data provide a molecular basis to explain at least part of the beneficial therapeutic properties of Shilajit and other humic extracts. (c) 2008 John Wiley & Sons, Ltd.

Flos Albiziae aqueous extract and its active constituent quercetin potentiate the hypnotic effect of pentobarbital via the serotonergic system

PubMed Central

YE, MENG-FEI; LIU, ZHENG; LOU, SHU-FANG; CHEN, ZHEN-YONG; YU, AI-YUE; LIU, CHUN-YAN; YU, CHAO-YANG; ZHANG, HUA-FANG; ZHANG, JIAN

2015-01-01

Flos albiziae (FA) is reportedly used for treatment of insomnia and anxiety in traditional medicine. The hypnotic effect of an extract of FA (FAE) and its constituent quercetin [2-(3,4-dihydroxyphenyl)-3,5,7-trihydroxy-4H-chromen-4-one, QR] was examined in mice. QR is a widely distributed natural flavonoid abundant in FA flowers and other tissues. The possible mechanisms underlying the hypnotic effects of FAE and QR were investigated using behavioral pharmacology. FAE and QR significantly potentiated pentobarbital-induced [50 mg/kg, intraperitoneal (ip)] sleep (prolonged sleeping time; shortened sleep latency) in a dose-dependent manner, and these effects were augmented by administration of 5-hydroxytryptophan (5-HTP), a precursor of 5-hydroxytryptamine. With a sub-hypnotic dose of pentobarbital (28 mg/kg, ip), FAE and QR significantly increased the rate of sleep onset and were synergistic with 5-HTP (2.5 mg/kg, ip). Pretreatment with p-chlorophenylalanine, an inhibitor of tryptophan hydroxylase, significantly decreased sleeping time and prolonged sleep latency in pentobarbital-treated mice, whereas FAE and QR significantly reversed this effect. Data show that FAE and QR have hypnotic activity, possibly mediated by the serotonergic system. The present study offers a rationale for the use of FA in treating sleep disorders associated with serotonin system dysfunction. PMID:26623026

Controllable Synthesis of a Smart Multifunctional Nanoscale Metal-Organic Framework for Magnetic Resonance/Optical Imaging and Targeted Drug Delivery.

PubMed

Gao, Xuechuan; Zhai, Manjue; Guan, Weihua; Liu, Jingjuan; Liu, Zhiliang; Damirin, Alatangaole

2017-02-01

As a result of their extraordinarily large surfaces and well-defined pores, the design of a multifunctional metal-organic framework (MOF) is crucial for drug delivery but has rarely been reported. In this paper, a novel drug delivery system (DDS) based on nanoscale MOF was developed for use in cancer diagnosis and therapy. This MOF-based tumor targeting DDS was fabricated by a simple postsynthetic surface modification process. First, magnetic mesoporous nanomaterial Fe-MIL-53-NH 2 was used for encapsulating the drug and served as a magnetic resonance contrast agent. Moreover, the Fe-MIL-53-NH 2 nanomaterial exhibited a high loading capacity for the model anticancer drug 5-fluorouracil (5-FU). Subsequently, the fluorescence imaging agent 5-carboxyfluorescein (5-FAM) and the targeting reagent folic acid (FA) were conjugated to the 5-FU-loaded Fe-MIL-53-NH 2 , resulting in the advanced DDS Fe-MIL-53-NH 2 -FA-5-FAM/5-FU. Owing to the multifunctional surface modification, the obtained DDS Fe-MIL-53-NH 2 -FA-5-FAM/5-FU shows good biocompatibility, tumor enhanced cellular uptake, strong cancer cell growth inhibitory effect, excellent fluorescence imaging, and outstanding magnetic resonance imaging capability. Taken together, this study integrates diagnostic and treatment aspects into a single platform by a simple and efficient strategy, aiming for facilitating new possibilities for MOF use for multifunctional drug delivery.

Individual differences in children's global motion sensitivity correlate with TBSS-based measures of the superior longitudinal fasciculus.

PubMed

Braddick, Oliver; Atkinson, Janette; Akshoomoff, Natacha; Newman, Erik; Curley, Lauren B; Gonzalez, Marybel Robledo; Brown, Timothy; Dale, Anders; Jernigan, Terry

2017-12-01

Reduced global motion sensitivity, relative to global static form sensitivity, has been found in children with many neurodevelopmental disorders, leading to the "dorsal stream vulnerability" hypothesis (Braddick et al., 2003). Individual differences in typically developing children's global motion thresholds have been shown to be associated with variations in specific parietal cortical areas (Braddick et al., 2016). Here, in 125 children aged 5-12years, we relate individual differences in global motion and form coherence thresholds to fractional anisotropy (FA) in the superior longitudinal fasciculus (SLF), a major fibre tract communicating between parietal lobe and anterior cortical areas. We find a positive correlation between FA of the right SLF and individual children's sensitivity to global motion coherence, while FA of the left SLF shows a negative correlation. Further analysis of parietal cortical area data shows that this is also asymmetrical, showing a stronger association with global motion sensitivity in the left hemisphere. None of these associations hold for an analogous measure of global form sensitivity. We conclude that a complex pattern of structural asymmetry, including the parietal lobe and the superior longitudinal fasciculus, is specifically linked to the development of sensitivity to global visual motion. This pattern suggests that individual differences in motion sensitivity are primarily linked to parietal brain areas interacting with frontal systems in making decisions on integrated motion signals, rather than in the extra-striate visual areas that perform the initial integration. The basis of motion processing deficits in neurodevelopmental disorders may depend on these same structures. Copyright © 2017 Elsevier Ltd. All rights reserved.

White Matter Disruptions in Schizophrenia Are Spatially Widespread and Topologically Converge on Brain Network Hubs

PubMed Central

Baker, Simon T.; Cropley, Vanessa L.; Bousman, Chad; Fornito, Alex; Cocchi, Luca; Fullerton, Janice M.; Rasser, Paul; Schall, Ulrich; Henskens, Frans; Michie, Patricia T.; Loughland, Carmel; Catts, Stanley V.; Mowry, Bryan; Weickert, Thomas W.; Shannon Weickert, Cynthia; Carr, Vaughan; Lenroot, Rhoshel; Pantelis, Christos; Zalesky, Andrew

2017-01-01

Abstract White matter abnormalities associated with schizophrenia have been widely reported, although the consistency of findings across studies is moderate. In this study, neuroimaging was used to investigate white matter pathology and its impact on whole-brain white matter connectivity in one of the largest samples of patients with schizophrenia. Fractional anisotropy (FA) and mean diffusivity (MD) were compared between patients with schizophrenia or schizoaffective disorder (n = 326) and age-matched healthy controls (n = 197). Between-group differences in FA and MD were assessed using voxel-based analysis and permutation testing. Automated whole-brain white matter fiber tracking and the network-based statistic were used to characterize the impact of white matter pathology on the connectome and its rich club. Significant reductions in FA associated with schizophrenia were widespread, encompassing more than 40% (234ml) of cerebral white matter by volume and involving all cerebral lobes. Significant increases in MD were also widespread and distributed similarly. The corpus callosum, cingulum, and thalamic radiations exhibited the most extensive pathology according to effect size. More than 50% of cortico-cortical and cortico-subcortical white matter fiber bundles comprising the connectome were disrupted in schizophrenia. Connections between hub regions comprising the rich club were disproportionately affected. Pathology did not differ between patients with schizophrenia and schizoaffective disorder and was not mediated by medication. In conclusion, although connectivity between cerebral hubs is most extensively disturbed in schizophrenia, white matter pathology is widespread, affecting all cerebral lobes and the cerebellum, leading to disruptions in the majority of the brain’s fiber bundles. PMID:27535082

Microstructural brain abnormalities in medication-free patients with major depressive disorder: a systematic review and meta-analysis of diffusion tensor imaging

PubMed Central

Jiang, Jing; Zhao, You-Jin; Hu, Xin-Yu; Du, Ming-Ying; Chen, Zi-Qi; Wu, Min; Li, Kai-Ming; Zhu, Hong-Yan; Kumar, Poornima; Gong, Qi-Yong

2017-01-01

Background Multiple meta-analyses of diffusion tensor imaging (DTI) studies have reported impaired white matter integrity in patients with major depressive disorder (MDD). However, owing to inclusion of medicated patients in these studies, it is difficult to conclude whether these reported alterations are associated with MDD or confounded by medication effects. A meta-analysis of DTI studies on medication-free (medication-naive and medication washout) patients with MDD would therefore be necessary to disentangle MDD-specific effects. Methods We analyzed white matter alterations between medication-free patients with MDD and healthy controls using anisotropic effect size–signed differential mapping (AES-SDM). We used DTI query software for fibre tracking. Results Both pooled and subgroup meta-analyses in medication washout patients showed robust fractional anisotropy (FA) reductions in white matter of the right cerebellum hemispheric lobule, body of the corpus callosum (CC) and bilateral superior longitudinal fasciculus III (SLF III), whereas FA reductions in the genu of the CC and right anterior thalamic projections were seen in only medication-naive patients. Fibre tracking showed that the main tracts with observed FA reductions included the right cerebellar tracts, body of the CC, bilateral SLF III and arcuate fascicle. Limitations The analytic techniques, patient characteristics and clinical variables of the included studies were heterogeneous; we could not exclude the effects of nondrug therapies owing to a lack of data. Conclusion By excluding the confounding influences of current medication status, findings from the present study may provide a better understanding of the underlying neuropathology of MDD. PMID:27780031

Altered microstructural connectivity of the superior cerebellar peduncle is related to motor dysfunction in children with autistic spectrum disorders.

PubMed

Hanaie, Ryuzo; Mohri, Ikuko; Kagitani-Shimono, Kuriko; Tachibana, Masaya; Azuma, Junji; Matsuzaki, Junko; Watanabe, Yoshiyuki; Fujita, Norihiko; Taniike, Masako

2013-10-01

Many studies have reported motor impairments in autistic spectrum disorders (ASD). However, the brain mechanism underlying motor impairment in ASD remains unclear. Recent neuroimaging studies have suggested that underconnectivity between the cerebellum and other brain regions contributes to the features of ASD. In this study, we investigated the microstructural integrity of the cerebellar pathways, including the superior, middle, and inferior cerebellar peduncles, of children with and without ASD by using diffusion tensor imaging (DTI) tractography to determine whether the microstructural integrity of the cerebellar pathways is related to motor function in children with ASD. Thirteen children with ASD and 11 age-, gender-, handedness-, and IQ-matched typically developing (TD) controls were enrolled in this study. DTI outcome measurements, such as fractional anisotropy (FA), axial diffusivity (AD), and radial diffusivity (RD), for the cerebellar pathways were calculated. The Movement Assessment Battery for Children 2 (M-ABC 2) was used for assessing motor functions. There were no significant differences between the two groups in RD. However, compared to the TD subjects, patients with ASD had a significantly lower FA in the right superior cerebellar peduncle and lower AD in the left superior cerebellar peduncle, in addition to a significantly lower score in ball skills and the total test score of M-ABC 2. There was a significant positive correlation between the total test score of M-ABC 2 and FA in the right superior cerebellar peduncle in the ASD group. These findings suggest that the altered microstructural integrity of the superior cerebellar peduncle may be related to motor impairment in ASD.

Analysis of the pattern of expression of the Fanconi anemia group C (Facc) gene during murine development

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

Krasnoshtein, F.; Buchwald, M.

1994-09-01

Fanconi anemia (FA) is an autosomal recessive disorder characterized by a variety of congenital and skeletal malformations, progressive pancytopanenia and predisposition to malignancies. FA cells display chromosomal instability and hypersensitivity to DNA-damaging agents. Both the human and the corresponding murine cDNAs have been cloned in our lab. Here we describe the expression of Facc during mouse development, using mRNA in situ hybridization. Our aim is to obtain clues on the possible function of the Facc gene product during development that may help elucidate basic defect(s) in FA. In addition, knowledge of the exact pattern of Facc expression will assist inmore » interpreting the phenotypes of mutant mice, currently being developed. In embryos the gene is diffusely expressed over the entire embryo, with higher hybridization levels in the mesenchyme and in both upper and lower extremities. Specific expression of Facc is seen in the perichondrium and marrow of long bones of hind limbs/hip; long bones of front limbs/shoulder region; developing digits of front and hind paws; and ribs. The signal is also detected in the following regions: cranial/frontal; facial/periorbital and maxillary/mandibular, hair follicles, diaphragm and lung. In addition, generalized Facc expression is seen during these embryonic stages. The pattern of Facc expression is consistent with the known skeletal abnormalities in FA patients, which include radial ray deformities, metacarpal hypoplasia, and abnormalities of lower limbs, ribs, head and face. The signal in the lung is consistent with the lung lobe absence and abnormal pulmonary drainage that have been detected in some FA patients. The sloped forehead and microcephaly in FA patients may have some association with the signal seen in the frontal region of the mouse cranium. Taken together, our results suggest that Facc is directly involved in the development of various embryonic tissues, particularly bone.« less

Functional analysis of the putative peroxidase domain of FANCA, the Fanconi anemia complementation group A protein.

PubMed

Ren, J; Youssoufian, H

2001-01-01

Fanconi anemia (FA) is an autosomal recessive disorder manifested by chromosomal breakage, birth defects, and susceptibility to bone marrow failure and cancer. At least seven complementation groups have been identified, and the genes defective in four groups have been cloned. The most common subtype is complementation group A. Although the normal functions of the gene products defective in FA cells are not completely understood, a clue to the function of the FA group A gene product (FANCA) was provided by the detection of limited homology in the amino terminal region to a class of heme peroxidases. We evaluated this hypothesis by mutagenesis and functional complementation studies. We substituted alanine residues for the most conserved FANCA residues in the putative peroxidase domain and tested their effects on known biochemical and cellular functions of FANCA. While the substitution mutants were comparable to wild-type FANCA with regard to their stability, subcellular localization, and interaction with FANCG, only the Trp(183)-to-Ala substitution (W183A) abolished the ability of FANCA to complement the sensitivity of FA group A cells to mitomycin C. By contrast, TUNEL assays for apoptosis after exposure to H2O2 showed no differences between parental FA group A cells, cells complemented with wild-type FANCA, and cells complemented with the W183A of FANCA. Moreover, semiquantitative RT-PCR analysis for the expression of the peroxide-sensitive heme oxygenase gene showed appropriate induction after H2O2 exposure. Thus, W183A appears to be essential for the in vivo activity of FANCA in a manner independent of its interaction with FANCG. Moreover, neither wild-type FANCA nor the W183A mutation appears to alter the peroxide-induced apoptosisor peroxide-sensing ability of FA group A cells. Copyright 2001 Academic Press.

A case report and literature review of Fanconi Anemia (FA) diagnosed by genetic testing.

PubMed

Solomon, Ponnumony John; Margaret, Priya; Rajendran, Ramya; Ramalingam, Revathy; Menezes, Godfred A; Shirley, Alph S; Lee, Seung Jun; Seong, Moon-Woo; Park, Sung Sup; Seol, Dodam; Seo, Soo Hyun

2015-05-08

Fanconi anemia (FA) is a genetically heterogeneous rare autosomal recessive disorder characterized by congenital malformations, hematological problems and predisposition to malignancies. The genes that have been found to be mutated in FA patients are called FANC. To date 16 distinct FANC genes have been reported. Among these, mutations in FANCA are the most frequent among FA patients worldwide which account for 60- 65%. In this study, a nine years old male child was brought to our hospital one year ago for opinion and advice. He was the third child born to consanguineous parents. The mutation analyses were performed for proband, parents, elder sibling and the relatives [maternal aunt and maternal aunt's son (cousin)]. Molecular genetic testing [targeted next-generation sequencing (MiSeq, Illumina method)] was performed by mutation analysis in 15 genes involved. Entire coding exons and their flanking regions of the genes were analysed. Sanger sequencing [(ABI 3730 analyzer by Applied Biosystems)] was performed using primers specific for 43 coding exons of the FANCA gene. A novel splice site mutation, c.3066 + 1G > T, (IVS31 + 1G > T), homozygote was detected by sequencing in the patient. The above sequence variant was identified in heterozygous state in his parents. Further, the above sequence variant was not identified in other family members (elder sibling, maternal aunt and cousin). It is concluded that genetic study should be done if possible in all the cases of suspected FA, including siblings, parents and close blood relatives. It will help us to plan appropriate treatment and also to select suitable donor for hematopoietic stem cell transplantation and to plan for genetic counseling. In addition to the case report, the main focus of this manuscript was to review literature on role of FANCA gene in FA since large number of FANCA mutations and polymorphisms have been identified.

Association of desaturase activity and C-reactive protein in European children.

PubMed

Wolters, Maike; Börnhorst, Claudia; Schwarz, Heike; Risé, Patrizia; Galli, Claudio; Moreno, Luis A; Pala, Valeria; Russo, Paola; Veidebaum, Toomas; Tornaritis, Michael; Fraterman, Arno; De Henauw, Stefaan; Eiben, Gabriele; Lissner, Lauren; Molnár, Dénes; Ahrens, Wolfgang

2017-01-01

Desaturase enzymes influence the fatty acid (FA) composition of body tissues and their activity affects the conversion rate of saturated to monounsaturated FA and of polyunsaturated FA (PUFA) to long-chain PUFA. Desaturase activity has further been shown to be associated with inflammation. We investigate the association between delta-9 (D9D), delta-6 (D6D) and delta-5 desaturase (D5D) activity and high-sensitive C-reactive protein (CRP) in young children. In the IDEFICS (Identification and prevention of dietary- and lifestyle-induced health effects in children and infants) cohort study children were examined at baseline (T0) and after 2 y (T1). D9D, D6D, and D5D activities were estimated from T0 product-precursor FA ratios. CRP was measured at T0 and T1. In a subsample of 1,943 children with available information on FA, CRP, and covariates, the cross-sectional and longitudinal associations of desaturase activity and CRP were analyzed. Cross-sectionally, a D9D increase of 0.01 units was associated with a 11% higher risk of having a serum CRP ≥ Percentile 75 (P75) (OR, 99% CI: 1.11 (1.01; 1.22)) whereas D6D and D5D were not associated with CRP. No significant associations were observed between baseline desaturase activity and CRP 2 y later. Cross-sectionally, our results indicate a positive association of D9D and CRP independent of weight status. High D9D activity may increase the risk of subclinical inflammation which is associated with metabolic disorders. As D9D expression increases with higher intake of saturated FA and carbohydrates, dietary changes may influence D9D activity and thus CRP. However, it remains to be investigated whether there is a causal relationship between D9D activity and CRP.

Neuroprotective potential of ferulic acid in the rotenone model of Parkinson’s disease

PubMed Central

Ojha, Shreesh; Javed, Hayate; Azimullah, Sheikh; Abul Khair, Salema B; Haque, M Emdadul

2015-01-01

Parkinson’s disease (PD) is a chronic, progressive, and the second most common form of neurodegenerative disorders. In order to explore novel agents for the treatment of PD, in the current study, we have evaluated the neuroprotective efficacy of ferulic acid (FA) using rotenone (ROT)-induced rat model of PD. ROT was administered 2.5 mg/kg body weight to male Wistar rats for 4 weeks to induce the PD. Since PD is progressive and chronic in nature, the paradigm for evaluating FA was based on chronic administration for 4 weeks at the dose of 50 mg/kg, 30 minutes prior to ROT administration. ROT administration caused significant reduction in endogenous antioxidants such as superoxide dismutase, catalase, and glutathione. ROT challenge-induced lipid peroxidation evidenced by increased malondialdehyde following perturbation of antioxidant defense. Apart from oxidative stress, ROT also activated proinflammatory cytokines and enhanced inflammatory mediators such as cyclooxygenase-2 and inducible nitric oxide synthase. The immunofluorescence analysis revealed a significant increase in the number of activated microglia and astrocytes accompanied by a significant loss of dopamine (DA) neurons in the substantia nigra pars compacta area upon ROT injection. However, treatment with FA rescued DA neurons in substantia nigra pars compacta area and nerve terminals in the striatum from the ROT insult. FA treatment also restored antioxidant enzymes, prevented depletion of glutathione, and inhibited lipid peroxidation. Following treatment with FA, the inflammatory mediators such as cyclooxygenase-2 and inducible nitric oxide synthase and proinflammatory cytokines were also reduced. Further, the results were supported by a remarkable reduction of Iba-1 and GFAP hyperactivity clearly suggests attenuation of microglial and astrocytic activation. Results of our study suggest that FA has promising neuroprotective effect against degenerative changes in PD, and the protective effects are mediated through its antioxidant and anti-inflammatory properties. PMID:26504373

A novel Trojan-horse targeting strategy to reduce the non-specific uptake of nanocarriers by non-cancerous cells.

PubMed

Shen, Zheyu; Wu, Hao; Yang, Sugeun; Ma, Xuehua; Li, Zihou; Tan, Mingqian; Wu, Aiguo

2015-11-01

One big challenge with active targeting of nanocarriers is non-specific binding between targeting molecules and non-target moieties expressed on non-cancerous cells, which leads to non-specific uptake of nanocarriers by non-cancerous cells. Here, we propose a novel Trojan-horse targeting strategy to hide or expose the targeting molecules of nanocarriers on-demand. The non-specific uptake by non-cancerous cells can be reduced because the targeting molecules are hidden in hydrophilic polymers. The nanocarriers are still actively targetable to cancer cells because the targeting molecules can be exposed on-demand at tumor regions. Typically, Fe3O4 nanocrystals (FN) as magnetic resonance imaging (MRI) contrast agents were encapsulated into albumin nanoparticles (AN), and then folic acid (FA) and pH-sensitive polymers (PP) were grafted onto the surface of AN-FN to construct PP-FA-AN-FN nanoparticles. Fourier transform infrared spectroscopy (FT-IR), dynamic light scattering (DLS), transmission electron microscope (TEM) and gel permeation chromatography (GPC) results confirm successful construction of PP-FA-AN-FN. According to difference of nanoparticle-cellular uptake between pH 7.4 and 5.5, the weight ratio of conjugated PP to nanoparticle FA-AN-FN (i.e. graft density) and the molecular weight of PP (i.e. graft length) are optimized to be 1.32 and 5.7 kDa, respectively. In vitro studies confirm that the PP can hide ligand FA to prevent it from binding to cells with FRα at pH 7.4 and shrink to expose FA at pH 5.5. In vivo studies demonstrate that our Trojan-horse targeting strategy can reduce the non-specific uptake of the PP-FA-AN-FN by non-cancerous cells. Therefore, our PP-FA-AN-FN might be used as an accurately targeted MRI contrast agent. Copyright © 2015 Elsevier Ltd. All rights reserved.

Desiccation by Foliar Deposition of Hygroscopic Aerosols may link Air Pollution to Forest Decline and Tree Mortality associated with Global-Change-Type Drought

NASA Astrophysics Data System (ADS)

Burkhardt, J.; Grantz, D. A.; Hunsche, M.; Pariyar, S.; Sutton, M. A.; Zinsmeister, D.

2016-12-01

Leaf surfaces are a major sink for atmospheric aerosol deposition. Plants benefit from aerosol associated nutrients and are able to increase deposition by leaf surface micromorphology. Recent studies have shown that deposited hygroscopic aerosols can also influence plant water relations. This might be an important issue even for remote forest ecosystems, given the strong anthropogenic influence on aerosol production and efficient atmospheric transport. We study processes of aerosol deposition to plant surfaces and their impact on water relations and drought tolerance, both for experimental particle amendment and for aerosol exclusion in filtered air (FA). FA plants experience an environment with < 10% concentration of hygroscopic aerosols compared to ambient air (AA), but no difference in trace gases. Increasing particle concentration leads to decreasing water use efficiency and increasing minimum epidermal conductance (gmin; a measure of uncontrolled water loss inversely related to drought tolerance). After particle amendment, anisohydric beech seedlings increased transpiration and maintained photosynthesis, while isohydric pine seedlings maintained transpiration and tended to reduce photosynthesis. FA seedlings of pine, oak, and fir showed lower gmin than corresponding AA seedlings. The results support the concept of hydraulic activation of stomata (HAS) and an associated wick action caused by leaf surface particles. Concentrated salt solutions formed by hygroscopicity even in unsaturated air may create a thin liquid film that penetrates the stomatal pore, allowing evaporation of liquid water at the leaf surface. Increased gmin suggests the significance of this process under ambient conditions. The direct impact of air pollution on plant drought tolerance is poorly integrated in current scenarios of forest decline and tree mortality, but might represent an important component.

White Matter Microstructure of the Human Mirror Neuron System Is Related to Symptom Severity in Adults with Autism

ERIC Educational Resources Information Center

Fründt, Odette; Schulz, Robert; Schöttle, Daniel; Cheng, Bastian; Thomalla, Götz; Braaß, Hanna; Ganos, Christos; David, Nicole; Peiker, Ina; Engel, Andreas K.; Bäumer, Tobias; Münchau, Alexander

2018-01-01

Mirror neuron system (MNS) dysfunctions might underlie deficits in autism spectrum disorders (ASD). Diffusion tensor imaging based probabilistic tractography was conducted in 15 adult ASD patients and 13 matched, healthy controls. Fractional anisotropy (FA) was quantified to assess group differences in tract-related white matter microstructure of…

High alpha feedback control for agile half-loop maneuvers of the F-18 airplane

NASA Technical Reports Server (NTRS)

Stalford, Harold

1988-01-01

A nonlinear feedback control law for the F/A-18 airplane that provides time-optimal or agile maneuvering of the half-loop maneuver at high angles of attack is given. The feedback control law was developed using the mathematical approach of singular perturbations, in which the control devices considered were conventional aerodynamic control surfaces and thrusting. The derived nonlinear control law was used to simulate F/A-18 half-loop maneuvers. The simulated results at Mach 0.6 and 0.9 compared well with pilot simulations conducted at NASA.

Development and characterization of surface engineered PPI dendrimers for targeted drug delivery.

PubMed

Kaur, Avleen; Jain, Keerti; Mehra, Neelesh Kumar; Jain, N K

2017-05-01

In this study, we reported folate-conjugated polypropylene imine dendrimers (FA-PPI) as efficient carrier for model anticancer drug, methotrexate (MTX), for pH-sensitive drug release, selective targeting to cancer cells, and anticancer activity. In the in vitro drug release studies this nanoconjugate of MTX showed initial rapid release followed by gradual slow release, and the drug release was found to be pH sensitive with greater release at acidic pH. The ex vivo investigations with human breast cancer cell lines, MCF-7, showed enhanced cytotoxicity of MTX-FA-PPI with significantly enhanced intracellular uptake. The biofate of nanoconjugate was determined in Wistar rat where MTX-FA-PPI showed 37.79-fold increase in the concentration of MTX in liver after 24 h in comparison with free MTX formulation.

Alterations of white matter integrity in adults with major depressive disorder: a magnetic resonance imaging study

PubMed Central

Zou, Ke; Huang, Xiaoqi; Li, Tao; Gong, Qiyong; Li, Zhe; Ou-yang, Luo; Deng, Wei; Chen, Qin; Li, Chunxiao; Ding, Yi; Sun, Xueli

2008-01-01

Objective The purpose of our study was to investigate alterations of white matter integrity in adults with major depressive disorder (MDD) using magnetic resonance imaging (MRI). Methods We performed diffusion tensor imaging with a 3T MRI scanner on 45 patients with major depression and 45 healthy controls matched for age, sex and education. Using a voxel-based analysis, we measured the fractional anisotropy (FA), and we investigated the differences between the patient and control groups. We examined the correlations between the microstructure abnormalities of white matter and symptom severity, age of illness onset and cumulative illness duration, respectively. Results We found a significant decrease in FA in the left hemisphere, including the anterior limb of the internal capsule and the inferior parietal portion of the superior longitudinal fasciculus, in patients with MDD compared with healthy controls. Diffusion tensor imaging measures in the left anterior limb of the internal capsule were negatively related to the severity of depressive symptoms, even after we controlled for age and sex. Conclusion Our findings provide new evidence of microstructural changes of white matter in non–late-onset adult depression. Our results complement those observed in late-life depression and support the hypothesis that the disruption of cortical– subcortical circuit integrity may be involved in the etiology of major depressive disorder. PMID:18982175

Using chromate to investigate the impact of natural organics on the surface reactivity of nanoparticulate magnetite

USGS Publications Warehouse

Swindle, Andrew L.; Cozzarelli, Isabelle M.; Elwood Madden, Andrew S.

2015-01-01

Chromate was used as a chemical probe to investigate the size-dependent influence of organics on nanoparticle surface reactivity. Magnetite–chromate sorption experiments were conducted with ∼90 and ∼6 nm magnetite nanoparticles in the presence and absence of fulvic acid (FA), natural organic matter (NOM), and isolated landfill leachate (LL). Results indicated that low concentrations (1 mg/L) of organics had no noticeable impact on chromate sorption, whereas concentrations of 50 mg/L or more resulted in decreased amounts of chromate sorption. The adsorption of organics onto the magnetite surfaces interfered equally with the ability of the 6 and 90 nm particles to sorb chromate from solution, despite the greater surface area of the smaller particles. Results indicate the presence of organics did not impact the redox chemistry of the magnetite–chromate system over the duration of the experiments (8 h), nor did the organics interact with the chromate in solution. Brunauer–Emmett–Teller (BET) and scanning electron microscopy (SEM) results indicate that the organics blocked the surface reactivity by occupying surface sites on the particles. The similarity of results with FA and NOM suggests that coverage of the reactive mineral surface is the main factor behind the inhibition of surface reactivity in the presence of organics.

Targeted disruption of exons 1 to 6 of the Fanconi Anemia group A gene leads to growth retardation, strain-specific microphthalmia, meiotic defects and primordial germ cell hypoplasia.

PubMed

Wong, Jasmine C Y; Alon, Noa; Mckerlie, Colin; Huang, Jun R; Meyn, M Stephen; Buchwald, Manuel

2003-08-15

Fanconi Anemia (FA) is an autosomal recessive disorder characterized by cellular hypersensitivity to DNA cross-linking agents. Recent studies suggest that FA proteins share a common pathway with BRCA proteins. To study the in vivo role of the FA group A gene (Fanca), gene-targeting techniques were used to generate Fanca(tm1Hsc) mice in which Fanca exons 1-6 were replaced by a beta-galactosidase reporter construct. Fanca(tm1.1Hsc) mice were generated by Cre-mediated removal of the neomycin cassette in Fanca(tm1Hsc) mice. Fanca(tm1.1Hsc) homozygotes display FA-like phenotypes including growth retardation, microphthalmia and craniofacial malformations that are not found in other Fanca mouse models, and the genetic background affects manifestation of certain phenotypes. Both male and female mice homozygous for Fanca mutation exhibit hypogonadism, and homozygous females demonstrate premature reproductive senescence and an increased incidence of ovarian cysts. We showed that fertility defects in Fanca(tm1.1Hsc) homozygotes might be related to a diminished population of primordial germ cells (PGCs) during migration into the gonadal ridges. We also found a high level of Fanca expression in pachytene spermatocytes. Fanca(tm1Hsc) homozygous males exhibited an elevated frequency of mispaired meiotic chromosomes and increased apoptosis in germ cells, implicating a role for Fanca in meiotic recombination. However, the localization of Rad51, Brca1, Fancd2 and Mlh1 appeared normal on Fanca(tm1Hsc) homozygous meiotic chromosomes. Taken together, our results suggest that the FA pathway plays a role in the maintenance of reproductive germ cells and in meiotic recombination.

Decreased and Increased Anisotropy along Major Cerebral White Matter Tracts in Preterm Children and Adolescents

PubMed Central

Ben-Shachar, Michal; Feldman, Heidi M.

2015-01-01

Premature birth is highly prevalent and associated with neurodevelopmental delays and disorders. Adverse outcomes, particularly in children born before 32 weeks of gestation, have been attributed in large part to white matter injuries, often found in periventricular regions using conventional imaging. To date, tractography studies of white matter pathways in children and adolescents born preterm have evaluated only a limited number of tracts simultaneously. The current study compares diffusion properties along 18 major cerebral white matter pathways in children and adolescents born preterm (n = 27) and full term (n = 19), using diffusion magnetic resonance imaging and tractography. We found that compared to the full term group, the preterm group had significantly decreased FA in segments of the bilateral uncinate fasciculus and anterior segments of the right inferior fronto-occipital fasciculus. Additionally, the preterm group had significantly increased FA in segments of the right and left anterior thalamic radiations, posterior segments of the right inferior fronto-occipital fasciculus, and the right and left inferior longitudinal fasciculus. Increased FA in the preterm group was generally associated with decreased radial diffusivity. These findings indicate that prematurity-related white matter differences in later childhood and adolescence do not affect all tracts in the periventricular zone and can involve both decreased and increased FA. Differences in the patterns of radial diffusivity and axial diffusivity suggest that the tissue properties underlying group FA differences may vary within and across white matter tracts. Distinctive diffusion properties may relate to variations in the timing of injury in the neonatal period, extent of white matter dysmaturity and/or compensatory processes in childhood. PMID:26560745

77 FR 34026 - Procurement List; Proposed Additions

Federal Register 2010, 2011, 2012, 2013, 2014

2012-06-08

... Industries of Southern California, Los Angeles, CA. Contracting Activity: Dept of the Air Force, FA4610 30... Type/Location: Secure Document Destruction Service, Navy Sea Systems (NAVSEA), Naval Surface Warfare...

Maternal Interleukin-6 concentration during pregnancy is associated with variation in frontolimbic white matter and cognitive development in early life.

PubMed

Rasmussen, Jerod M; Graham, Alice M; Entringer, Sonja; Gilmore, John H; Styner, Martin; Fair, Damien A; Wadhwa, Pathik D; Buss, Claudia

2018-04-11

Maternal inflammation during pregnancy can alter the trajectory of fetal brain development and increase risk for offspring psychiatric disorders. However, the majority of relevant research to date has been conducted in animal models. Here, in humans, we focus on the structural connectivity of frontolimbic circuitry as it is both critical for socioemotional and cognitive development, and commonly altered in a range of psychiatric disorders associated with intrauterine inflammation. Specifically, we test the hypothesis that elevated maternal concentration of the proinflammatory cytokine interleukin-6 (IL-6) during pregnancy will be associated with variation in microstructural properties of this circuitry in the neonatal period and across the first year of life. Pregnant mothers were recruited in early pregnancy and maternal blood samples were obtained for assessment of maternal IL-6 concentrations in early (12.6 ± 2.8 weeks [S.D.]), mid (20.4 ± 1.5 weeks [S.D.]) and late (30.3 ± 1.3 weeks [S.D.]) gestation. Offspring brain MRI scans were acquired shortly after birth (N = 86, scan age = 3.7 ± 1.7 weeks [S.D.]) and again at 12-mo age (N = 32, scan age = 54.0 ± 3.1 weeks [S.D.]). Diffusion Tensor Imaging (DTI) was used to characterize fractional anisotropy (FA) along the left and right uncinate fasciculus (UF), representing the main frontolimbic fiber tract. In N = 30 of the infants with serial MRI data at birth and 12-mo age, cognitive and socioemotional developmental status was characterized using the Bayley Scales of Infant Development. All analyses tested for potentially confounding influences of household income, prepregnancy Body-Mass-Index, obstetric risk, smoking during pregnancy, and infant sex, and outcomes at 12-mo age were additionally adjusted for the quality of the postnatal caregiving environment. Maternal IL-6 concentration (averaged across pregnancy) was prospectively and inversely associated with FA (suggestive of reduced integrity under high inflammatory conditions) in the newborn offspring (bi-lateral, p < 0.01) in the central portion of the UF proximal to the amygdala. Furthermore, maternal IL-6 concentration was positively associated with rate of FA increase across the first year of life (bi-lateral, p < 0.05), resulting in a null association between maternal IL-6 and UF FA at 12-mo age. Maternal IL-6 was also inversely associated with offspring cognition at 12-mo age, and this association was mediated by FA growth across the first year of postnatal life. Findings from the current study support the premise that susceptibility for cognitive impairment and potentially psychiatric disorders may be affected in utero, and that maternal inflammation may constitute an intrauterine condition of particular importance in this context. Copyright © 2018 Elsevier Inc. All rights reserved.

Demographic, socioeconomic, and behavioral factors affecting patterns of tooth decay in the permanent dentition: Principal components and factor analyses

PubMed Central

Shaffer, John R.; Polk, Deborah E.; Feingold, Eleanor; Wang, Xiaojing; Cuenco, Karen T.; Weeks, Daniel E.; DeSensi, Rebecca S.; Weyant, Robert J.; Crout, Richard; McNeil, Daniel W.; Marazita, Mary L.

2012-01-01

Objectives Dental caries of the permanent dentition is a multi-factorial disease resulting from the complex interplay of endogenous and environmental risk factors. The disease is not easily quantified due to the innumerable possible combinations of carious lesions across individual tooth surfaces of the permanent dentition. Global measures of decay, such as the DMFS index (which was developed for surveillance applications), may not be optimal for studying the epidemiology of dental caries because they ignore the distinct patterns of decay across the dentition. We hypothesize that specific risk factors may manifest their effects on specific tooth surfaces leading to patterns of decay that can be identified and studied. In this study we utilized two statistical methods of extracting patterns of decay from surface-level caries data in order to create novel phenotypes with which to study the risk factors affecting dental caries. Methods Intra-oral dental examinations were performed on 1,068 participants aged 18 to 75 years to assess dental caries. The 128 tooth surfaces of the permanent dentition were scored as carious or not and used as input for principal components analysis (PCA) and factor analysis (FA), two methods of identifying underlying patterns without a priori knowledge of the patterns. Demographic (age, sex, birth year, race/ethnicity, and educational attainment), anthropometric (height, body mass index, waist circumference), endogenous (saliva flow), and environmental (tooth brushing frequency, home water source, and home water fluoride) risk factors were tested for association with the caries patterns identified by PCA and FA, as well as DMFS, for comparison. The ten strongest patterns (i.e., those that explain the most variation in the data set) extracted by PCA and FA were considered. Results The three strongest patterns identified by PCA reflected (i) global extent of decay (i.e., comparable to DMFS index), (ii) pit and fissure surface caries, and (iii) smooth surface caries, respectively. The two strongest patterns identified by FA corresponded to (i) pit and fissure surface caries and (ii) maxillary incisor caries. Age and birth year were significantly associated with several patterns of decay, including global decay/DMFS index. Sex, race, educational attainment, and tooth brushing were each associated with specific patterns of decay, but not with global decay/DMFS index. Conclusions Taken together, these results support the notion that caries experience is separable into patterns attributable to distinct risk factors. This study demonstrates the utility of such novel caries patterns as new outcomes for exploring the complex, multifactorial nature of dental caries. PMID:23106439

Demographic, socioeconomic, and behavioral factors affecting patterns of tooth decay in the permanent dentition: principal components and factor analyses.

PubMed

Shaffer, John R; Polk, Deborah E; Feingold, Eleanor; Wang, Xiaojing; Cuenco, Karen T; Weeks, Daniel E; DeSensi, Rebecca S; Weyant, Robert J; Crout, Richard; McNeil, Daniel W; Marazita, Mary L

2013-08-01

Dental caries of the permanent dentition is a multifactorial disease resulting from the complex interplay of endogenous and environmental risk factors. The disease is not easily quantitated due to the innumerable possible combinations of carious lesions across individual tooth surfaces of the permanent dentition. Global measures of decay, such as the DMFS index (which was developed for surveillance applications), may not be optimal for studying the epidemiology of dental caries because they ignore the distinct patterns of decay across the dentition. We hypothesize that specific risk factors may manifest their effects on specific tooth surfaces leading to patterns of decay that can be identified and studied. In this study, we utilized two statistical methods of extracting patterns of decay from surface-level caries data to create novel phenotypes with which to study the risk factors affecting dental caries. Intra-oral dental examinations were performed on 1068 participants aged 18-75 years to assess dental caries. The 128 tooth surfaces of the permanent dentition were scored as carious or not and used as input for principal components analysis (PCA) and factor analysis (FA), two methods of identifying underlying patterns without a priori knowledge of the patterns. Demographic (age, sex, birth year, race/ethnicity, and educational attainment), anthropometric (height, body mass index, waist circumference), endogenous (saliva flow), and environmental (tooth brushing frequency, home water source, and home water fluoride) risk factors were tested for association with the caries patterns identified by PCA and FA, as well as DMFS, for comparison. The ten strongest patterns (i.e. those that explain the most variation in the data set) extracted by PCA and FA were considered. The three strongest patterns identified by PCA reflected (i) global extent of decay (i.e. comparable to DMFS index), (ii) pit and fissure surface caries and (iii) smooth surface caries, respectively. The two strongest patterns identified by FA corresponded to (i) pit and fissure surface caries and (ii) maxillary incisor caries. Age and birth year were significantly associated with several patterns of decay, including global decay/DMFS index. Sex, race, educational attainment, and tooth brushing were each associated with specific patterns of decay, but not with global decay/DMFS index. Taken together, these results support the notion that caries experience is separable into patterns attributable to distinct risk factors. This study demonstrates the utility of such novel caries patterns as new outcomes for exploring the complex, multifactorial nature of dental caries. © 2012 John Wiley & Sons A/S. Published by John Wiley & Sons Ltd.

Stone decay assessment of the Madrid's Royal Palace (Spain) by means of ultrasound and magnetometric prospection

NASA Astrophysics Data System (ADS)

Fort, R.; Alvarez de Buergo, M.

2012-04-01

The architrave of the entablature of the 4 façades of the Palace was built in a limestone known as Colmenar stone (biomicrite), a traditional material used for construction in Madrid. This stone shows such petrophysical properties that make it resistant to decay processes. Despite its high quality, the ashlars of the architrave have undergone fissuring processes resulting on fragments fall, some of them being blocks weighing more than 300 Kg, with the consequent risk for visitors and passers-by. Fissures were caused by the presence of metallic elements (iron-based) used to tie ashlars. These elements, which could have performed properly in absence of water, underwent oxidation processes due to the water entrance, exerting significant pressures inside the stone that derive into fractures with their planes being almost parallel to the façade surface. Once verified that the presence of these metallic elements, and their oxidation, was the cause of the ashlars fissuring, an inspection of the building façades architrave was performed by using two portable and non destructive techniques: magnetometry for detecting iron elements, and ultrasound velocity prospection for detecting non visible stone fissures behind the surface. This survey will allow defining the guidelines for a restoration intervention. The inspection of the architrave consisted of analysing around 1100 ashlars (circa 600 meters long were surveyed), during a lapse of time of one year, in 4 survey campaigns, one for each façade, with the aid of a mobile and self-operating that allows to reach up to 40 m high. Results from the magnetometry prospection made possible to locate metallic elements (flat bars and cramps), and sometimes the flat bars overlapping. Such bars are usually located at 3-5 cm deep from the surface, just below the freeze and in a case cut in the architrave limestone. In the areas of flat bars overlapping, a depth from the surface into the façade of 8-10 cm was measured. Such bars were several meters long, tieing several ashlars, from 55 to 65 mm wide, and 15-20 mm thick. In vaulted areas of the frieze, iron beams were detected, of around 9 cm thick, as well as iron angle bars behind the mentioned iron beams, vertically arranged and going through the architrave. The ultrasound propagation velocity survey in all the architrave ashlars was carried out by means of the indirect or surface mode, using a measuring net of 15 cm side and 20 to 30 readings in each element. Results obtained allowed detecting fissures inside the ashlars non visible at the stone surface. Main fissures were located in areas of cramp-stone coupling. Therefore, this technique was sucessful in locating architrave ashlars with risk of fall, and thus it made possible to plan the structural intervention to consolidate these elements by micro reinforcement with stainless materials (e.g. glass fiber).

Gaseous mercury from curing concretes that contain fly ash: laboratory measurements

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

Danold W. Golightly; Ping Sun; Chin-Min Cheng

2005-08-01

Total gaseous mercury in headspace air was measured for enclosed concretes dry curing at 40 C for intervals of 2, 28, and 56 days. Release of mercury was confirmed for ordinary Portland cement concrete (OPC) and three concretes in which class F fly ash from coal-combustion substituted for a fraction of the cement: (a) 33% fly ash (FA33), (b) 55% fly ash (FA55), and (c) 33% fly ash plus 0.5% mercury-loaded powdered activated carbon (HgPAC). Mean rates of mercury release (0.10-0.43 ng/day per kg of concrete) over the standard first 28 days of curing followed the order OPC {lt} FA33more » {approximately} FA55 {lt} HgPAC. The mercury flux from exposed surfaces of these concretes ranged from 1.9 {+-} 0.5 to 8.1 {+-} 2.0 ng/m{sup 2}/h, values similar to the average flux for multiple natural substrates in Nevada, 4.2 {+-} 1.4 ng/m{sup 2}/h, recently published by others. Air sampling extending for 28 days beyond the initial 28-day maturation for OPC, FA55, and HgPAC suggested that the average Hg release rate by OPC is constant over 56 days and that mercury release rates for FA55 and HgPAC may ultimately diminish to levels exhibited by OPC concrete. The release of mercury from all samples was less than 0.1% of total mercury content over the initial curing period, implying that nearly all of the mercury was retained in the concrete. 20 refs., 3 figs., 3 tabs.« less

Use of LiDAR for calculating solar irradiance on roofs and façades of buildings at city scale: Methodology, validation, and analysis

NASA Astrophysics Data System (ADS)

Cheng, Liang; Xu, Hao; Li, Shuyi; Chen, Yanming; Zhang, Fangli; Li, Manchun

2018-04-01

As the rate of urbanization continues to accelerate, the utilization of solar energy in buildings plays an increasingly important role in sustainable urban development. For this purpose, we propose a LiDAR-based joint approach for calculating the solar irradiance incident on roofs and façades of buildings at city scale, which includes a methodology for calculating solar irradiance, the validation of the proposed method, and analysis of its application. The calculation of surface irradiance on buildings may then inform photovoltaic power generation simulations, architectural design, and urban energy planning. Application analyses of the proposed method in the experiment area found that: (1) Global and direct irradiations vary significantly by hour, day, month and season, both following the same trends; however, diffuse irradiance essentially remains unchanged over time. (2) Roof irradiation, but not façade irradiation, displays distinct time-dependent patterns. (3) Global and direct irradiations on roofs are highly correlated with roof aspect and slope, with high global and direct irradiations observed on roofs of aspect 100-250° and slopes of 0-60°, whereas diffuse irradiation on roofs is only affected by roof slope. (4) The façade of a building receives higher levels of global and direct irradiations if facing southeast, south, and southwest; however, diffuse irradiation remains constant regardless of façade orientation.

Malfunction of nuclease ERCC1-XPF results in diverse clinical manifestations and causes Cockayne syndrome, xeroderma pigmentosum, and Fanconi anemia.

PubMed

Kashiyama, Kazuya; Nakazawa, Yuka; Pilz, Daniela T; Guo, Chaowan; Shimada, Mayuko; Sasaki, Kensaku; Fawcett, Heather; Wing, Jonathan F; Lewin, Susan O; Carr, Lucinda; Li, Tao-Sheng; Yoshiura, Koh-ichiro; Utani, Atsushi; Hirano, Akiyoshi; Yamashita, Shunichi; Greenblatt, Danielle; Nardo, Tiziana; Stefanini, Miria; McGibbon, David; Sarkany, Robert; Fassihi, Hiva; Takahashi, Yoshito; Nagayama, Yuji; Mitsutake, Norisato; Lehmann, Alan R; Ogi, Tomoo

2013-05-02

Cockayne syndrome (CS) is a genetic disorder characterized by developmental abnormalities and photodermatosis resulting from the lack of transcription-coupled nucleotide excision repair, which is responsible for the removal of photodamage from actively transcribed genes. To date, all identified causative mutations for CS have been in the two known CS-associated genes, ERCC8 (CSA) and ERCC6 (CSB). For the rare combined xeroderma pigmentosum (XP) and CS phenotype, all identified mutations are in three of the XP-associated genes, ERCC3 (XPB), ERCC2 (XPD), and ERCC5 (XPG). In a previous report, we identified several CS cases who did not have mutations in any of these genes. In this paper, we describe three CS individuals deficient in ERCC1 or ERCC4 (XPF). Remarkably, one of these individuals with XP complementation group F (XP-F) had clinical features of three different DNA-repair disorders--CS, XP, and Fanconi anemia (FA). Our results, together with those from Bogliolo et al., who describe XPF alterations resulting in FA alone, indicate a multifunctional role for XPF. Copyright © 2013 The American Society of Human Genetics. Published by Elsevier Inc. All rights reserved.

Dry sliding behavior of aluminum alloy 8011 with 12% fly ash composites

NASA Astrophysics Data System (ADS)

Magibalan, S.; Senthilkumar, P.; Palanivelu, R.; Senthilkumar, C.; Shivasankaran, N.; Prabu, M.

2018-05-01

This research focused on the fabrication of aluminum alloy 8011 with 12% fly ash (FA) composite (AA8011%–12% FA) using the stir casting method. A three-level central composite design experiment was developed using response surface methodology with various parameters such as load, time, and sliding velocity varied in the range of 5 to 15 N, 5 to 15 min, and 1.5 to 4.5 m.s‑1, respectively. Dry sliding wear tests were performed as per the experimental design using a pin on disc at room temperature. The obtained regression result indicated that the developed model performed well in relating the wear process parameters and predicted the wear behavior of the composite. The surface plot showed that the wear rate increases with increase in load, time, and sliding velocity. Hardness was evaluated by Vickers hardness testing machine. Moreover, the surface morphology of the worn-out composite was examined using a scanning electron microscope.

Phytoremediation of heavy metals from fly ash pond by Azolla caroliniana.

PubMed

Pandey, Vimal Chandra

2012-08-01

Abundance of naturally growing Azolla caroliniana (water fern) on the surface of metal enriched fly ash (FA) pond reflects its toxitolerant characteristics. Results indicate the efficiency of A. caroliniana for phytoremediation of FA pond because of its higher bioconcentration factor. The metal concentration ranged from 175 to 538 and 86 to 753mgkg(-1) in roots and fronds, respectively. Bioconcentration factor (BCF) values of all metals in root and frond ranged from 1.7 to18.6 and 1.8 to 11.0, respectively, which were greater than one and indicates the metal accumulation potential of A. caroliniana. Translocation factor (TF) ranged from 0.37 to 1.4 for various heavy metals. The field result proved that A. caroliniana is a potential accumulator for the examined heavy metals and can be used for phytoremediation of FA pond. Copyright © 2012 Elsevier Inc. All rights reserved.

Impact of humic/fulvic acid on the removal of heavy metals from aqueous solutions using nanomaterials: a review.

PubMed

Tang, Wang-Wang; Zeng, Guang-Ming; Gong, Ji-Lai; Liang, Jie; Xu, Piao; Zhang, Chang; Huang, Bin-Bin

2014-01-15

Nowadays nanomaterials have been widely used to remove heavy metals from water/wastewater due to their large surface area and high reactivity. Humic acid (HA) and fulvic acid (FA) exist ubiquitously in aquatic environments and have a variety of functional groups which allow them to complex with metal ions and interact with nanomaterials. These interactions can not only alter the environmental behavior of nanomaterials, but also influence the removal and transportation of heavy metals by nanomaterials. Thus, the interactions and the underlying mechanisms involved warrant specific investigations. This review outlined the effects of HA/FA on the removal of heavy metals from aqueous solutions by various nanomaterials, mainly including carbon-based nanomaterials, iron-based nanomaterials and photocatalytic nanomaterials. Moreover, mechanisms involved in the interactions were discussed and potential environmental implications of HA/FA to nanomaterials and heavy metals were evaluated. © 2013.

Analysis of Tangential Slot Blowing on F/A-18 Isolated Forebody

NASA Technical Reports Server (NTRS)

Gee, Ken; Rizk, Yehia M.; Schiff, Lewis B.

1995-01-01

The generation of significant side forces and yawing moments on an F/A-18 fuselage through tangential slot blowing is analyzed using computational fluid dynamics. The effects of freestream Mach number, jet exit conditions, jet length, and jet location are studied. The effects of over- and underblowing on force and moment production are analyzed. Non-time-accurate solutions are obtained to determine the steady-state side forces, yawing moments, and surface pressure distributions generated by tangential slot blowing. Time-accurate solutions are obtained to study the force onset time lag of tangential slot blowing. Comparison with available experimental data from full-scale wind-tunnel and subscale wind-tunnel tests are made. This computational analysis complements the experimental results and provides a detailed understanding of the effects of tangential slot blowing on the flowfield about the isolated F/A-18 forebody. Additionally, it extends the slot-blowing database to transonic maneuvering Mach numbers.

Water flow pathway and the organic carbon discharge during rain storm events in a coniferous forested head watershed, Tokyo, central Japan

NASA Astrophysics Data System (ADS)

Moriizumi, Mihoko; Terajima, Tomomi

2010-05-01

The current intense discussion of the green house effect, that has been one of the main focuses on the carbon cycle in environmental systems of the earth, seems to be weakened the importance related to the effect of carbonic materials on substance movement in the aquatic environments; though it has just begun to be referred recently. Because dissolved organic carbon (DOC) in stream flows believes to play a main role of the carbon cycle in the fresh water environment, seasonal changes in DOC discharge were investigated in catchments with various scale and land use, especially in forested catchments which are one of the important sources of DOC. In order to understand the fundamental characteristics of the discharge of dissolved organic materials, stream flows, DOC, and fulvic acid like materials (FA) included in stream flows were measured in a coniferous forested head watershed. The watershed is located at the southeast edge of the Kanto mountain and is 40 km west of Tokyo with the elevation from 720 to 820 m and mean slope gradient of 38 degrees. Geology of the watershed is underlain by the sequence of mud and sand stones in Jurassic and the soil in the watershed is Cambisol (Inceptisols). The watershed composes of a dense cypress and cedar forest of 45 years old with poor understory vegetation. Observations were carried out for 6 rain storms of which the total precipitations ranged between 16.2 and 117.4 mm. The magnitude of the storms was classified into small, middle, and big events on the basis of the total precipitation of around 20, 40, and more than 70 mm. Stream flows were collected during the storm events by 1 hour interval and were passed through the 0.45 μm filters, and then the DOC concentrations in the flows were measured with a total organic carbon analyzer. The relative concentrations of fulvic acid (FA) in the flows were monitored with three dimensional excitations emission matrix fluorescence spectroscopy, because fulvic acid shows distinctive fluorescence peaks at around the excitation wave length of 340 nm and emission wave length of 440 nm. The timing of the peaks in DOC and FA occurred simultaneously or within 30 minutes prior to those in the stream flows. The relationship between DOC and stream flow showed linear correlations with various gradients in each event. However, the relationship between FA and stream flow showed the linear correlations only for the small and middle events and clockwise hysteresis relations occurred in the big storm events. The relationship between DOC and FA showed the linear correlations both for the extracted water of the shallow soil and for stream base flow composed mostly of groundwater discharge. However, the relationship in the storm flow closely distributed at that in the extracted water of the shallow soil. This thing reveals that DOC and FA were mainly flashed out from the shallow soil during the rain storm events. The quick rising and recession of the fulvic acid was likely provided by quick rain water discharge through the surface or near surface of the slope. However, the overland flow were rare in the watershed during the rain storms. This indicates that the rapid shallow subsurface flow, passed mainly through preferential flow pathways at the slope surface within the loose litter and root-permeated zone, was the main cause of the difference in discharge regimes between DOC and FA. The shallow subsurface flow may have flushed the FA in the near-surface of the soil, and then the relatively predominant discharge of DOC must have been caused during the big rain storm event.

Heritable patterns of tooth decay in the permanent dentition: principal components and factor analyses.

PubMed

Shaffer, John R; Feingold, Eleanor; Wang, Xiaojing; Tcuenco, Karen T; Weeks, Daniel E; DeSensi, Rebecca S; Polk, Deborah E; Wendell, Steve; Weyant, Robert J; Crout, Richard; McNeil, Daniel W; Marazita, Mary L

2012-03-09

Dental caries is the result of a complex interplay among environmental, behavioral, and genetic factors, with distinct patterns of decay likely due to specific etiologies. Therefore, global measures of decay, such as the DMFS index, may not be optimal for identifying risk factors that manifest as specific decay patterns, especially if the risk factors such as genetic susceptibility loci have small individual effects. We used two methods to extract patterns of decay from surface-level caries data in order to generate novel phenotypes with which to explore the genetic regulation of caries. The 128 tooth surfaces of the permanent dentition were scored as carious or not by intra-oral examination for 1,068 participants aged 18 to 75 years from 664 biological families. Principal components analysis (PCA) and factor analysis (FA), two methods of identifying underlying patterns without a priori surface classifications, were applied to our data. The three strongest caries patterns identified by PCA recaptured variation represented by DMFS index (correlation, r = 0.97), pit and fissure surface caries (r = 0.95), and smooth surface caries (r = 0.89). However, together, these three patterns explained only 37% of the variability in the data, indicating that a priori caries measures are insufficient for fully quantifying caries variation. In comparison, the first pattern identified by FA was strongly correlated with pit and fissure surface caries (r = 0.81), but other identified patterns, including a second pattern representing caries of the maxillary incisors, were not representative of any previously defined caries indices. Some patterns identified by PCA and FA were heritable (h(2) = 30-65%, p = 0.043-0.006), whereas other patterns were not, indicating both genetic and non-genetic etiologies of individual decay patterns. This study demonstrates the use of decay patterns as novel phenotypes to assist in understanding the multifactorial nature of dental caries.

Eigenanatomy on Fractional Anisotropy Imaging Provides White Matter Anatomical Features Discriminating Between Alzheimer's Disease and Late Onset Bipolar Disorder.

PubMed

Besga, Ariadna; Chyzhyk, Darya; González-Ortega, Itxaso; Savio, Alexandre; Ayerdi, Borja; Echeveste, Jon; Graña, Manuel; González-Pinto, Ana

2016-01-01

Late Onset Bipolar Disorder (LOBD) is the arousal of Bipolar Disorder (BD) at old age (>60) without any previous history of disorders. LOBD is often difficult to distinguish from degenerative dementias, such as Alzheimer Disease (AD), due to comorbidities and common cognitive symptoms. Moreover, LOBD prevalence is increasing due to population aging. Biomarkers extracted from blood plasma are not discriminant because both pathologies share pathophysiological features related to neuroinflammation, therefore we look for anatomical features highly correlated with blood biomarkers that allow accurate diagnosis prediction. This may shed some light on the basic biological mechanisms leading to one or another disease. Moreover, accurate diagnosis is needed to select the best personalized treatment. We look for white matter features which are correlated with blood plasma biomarkers (inflammatory and neurotrophic) discriminating LOBD from AD. A sample of healthy controls (HC) (n=19), AD patients (n=35), and BD patients (n=24) has been recruited at the Alava University Hospital. Plasma biomarkers have been obtained at recruitment time. Diffusion weighted (DWI) magnetic resonance imaging (MRI) are obtained for each subject. DWI is preprocessed to obtain diffusion tensor imaging (DTI) data, which is reduced to fractional anisotropy (FA) data. In the selection phase, eigenanatomy finds FA eigenvolumes maximally correlated with plasma biomarkers by partial sparse canonical correlation analysis (PSCCAN). In the analysis phase, we take the eigenvolume projection coefficients as the classification features, carrying out cross-validation of support vector machine (SVM) to obtain discrimination power of each biomarker effects. The John Hopkins Universtiy white matter atlas is used to provide anatomical localizations of the detected feature clusters. Classification results show that one specific biomarker of oxidative stress (malondialdehyde MDA) gives the best classification performance ( accuracy 85%, F-score 86%, sensitivity, and specificity 87%, ) in the discrimination of AD and LOBD. Discriminating features appear to be localized in the posterior limb of the internal capsule and superior corona radiata. It is feasible to support contrast diagnosis among LOBD and AD by means of predictive classifiers based on eigenanatomy features computed from FA imaging correlated to plasma biomarkers. In addition, white matter eigenanatomy localizations offer some new avenues to assess the differential pathophysiology of LOBD and AD.

Diffusion tensor imaging in evaluation of human skeletal muscle injury.

PubMed

Zaraiskaya, Tatiana; Kumbhare, Dinesh; Noseworthy, Michael D

2006-08-01

To explore the capability and reliability of diffusion tensor magnetic resonance imaging (DTI) in the evaluation of human skeletal muscle injury. DTI of four patients with gastrocnemius and soleus muscles injuries was compared to eight healthy controls. Imaging was performed using a GE 3.0T short-bore scanner. A diffusion-weighted 2D spin echo echo-planar imaging (EPI) pulse sequence optimized for skeletal muscle was used. From a series of axially acquired diffusion tensor images the diffusion tensor eigenparameters (eigenvalues and eigenvectors), fractional anisotropy (FA), and apparent diffusion coefficient (ADC) were calculated and compared for injured and healthy calf muscles. Two dimensional (2D) projection maps of the principal eigenvectors were plotted to visualize the healthy and pathologic muscle fiber architectures. Clear differences in FA and ADC were observed in injured skeletal muscle, compared to healthy controls. Mean control FA was 0.23 +/- 0.02 for medial and lateral gastrocnemius (mg and lg) muscles, and 0.20 +/- 0.02 for soleus (sol) muscles. In all patients FA values were reduced compared to controls, to as low as 0.08 +/- 0.02. The ADC in controls ranged from 1.41 to 1.31 x 10(-9) m(2)/second, while in patients this was consistently higher. The 2D projection maps revealed muscle fiber disorder in injured calves, while in healthy controls the 2D projection maps show a well organized (ordered) fiber structure. DTI is a suitable method to assess human calf muscle injury.

Neuropsychiatry and White Matter Microstructure in Huntington’s Disease

PubMed Central

Gregory, Sarah; Scahill, Rachael I.; Seunarine, Kiran K.; Stopford, Cheryl; Zhang, Hui; Zhang, Jiaying; Orth, Michael; Durr, Alexandra; Roos, Raymund A.C.; Langbehn, Douglas R.; Long, Jeffrey D.; Johnson, Hans; Rees, Geraint; Tabrizi, Sarah J.; Craufurd, David

2015-01-01

Abstract Background: Neuropsychiatric symptoms in Huntington’s disease (HD) are often evident prior to clinical diagnosis. Apathy is highly correlated with disease progression, while depression and irritability occur at different stages of the disease, both before and after clinical onset. Little is understood about the neural bases of these neuropsychiatric symptoms and to what extent those neural bases are analogous to neuropsychiatric disorders in the general population. Objective: We used Diffusion Tensor Imaging (DTI) to investigate structural connectivity between brain regions and any putative microstructural changes associated with depression, apathy and irritability in HD. Methods: DTI data were collected from 39 premanifest and 45 early-HD participants in the Track-HD study and analysed using whole-brain Tract-Based Spatial Statistics. We used regression analyses to identify white matter tracts whose structural integrity (as measured by fractional anisotropy, FA) was correlated with HADS-depression, PBA-apathy or PBA-irritability scores in gene-carriers and related to cumulative probability to onset (CPO). Results: For those with the highest CPO, we found significant correlations between depression scores and reduced FA in the splenium of the corpus callosum. In contrast, those with lowest CPO demonstrated significant correlations between irritability scores and widespread FA reductions. There was no significant relationship between apathy and FA throughout the whole brain. Conclusions: We demonstrate that white matter changes associated with both depression and irritability in HD occur at different stages of disease progression concomitant with their clinical presentation. PMID:26443926

Concomitant fractional anisotropy and volumetric abnormalities in temporal lobe epilepsy: cross-sectional evidence for progressive neurologic injury.

PubMed

Keller, Simon S; Schoene-Bake, Jan-Christoph; Gerdes, Jan S; Weber, Bernd; Deppe, Michael

2012-01-01

In patients with temporal lobe epilepsy and associated hippocampal sclerosis (TLEhs) there are brain abnormalities extending beyond the presumed epileptogenic zone as revealed separately in conventional magnetic resonance imaging (MRI) and MR diffusion tensor imaging (DTI) studies. However, little is known about the relation between macroscopic atrophy (revealed by volumetric MRI) and microstructural degeneration (inferred by DTI). For 62 patients with unilateral TLEhs and 68 healthy controls, we determined volumes and mean fractional anisotropy (FA) of ipsilateral and contralateral brain structures from T1-weighted and DTI data, respectively. We report significant volume atrophy and FA alterations of temporal lobe, subcortical and callosal regions, which were more diffuse and bilateral in patients with left TLEhs relative to right TLEhs. We observed significant relationships between volume loss and mean FA, particularly of the thalamus and putamen bilaterally. When corrected for age, duration of epilepsy was significantly correlated with FA loss of an anatomically plausible route - including ipsilateral parahippocampal gyrus and temporal lobe white matter, the thalamus bilaterally, and posterior regions of the corpus callosum that contain temporal lobe fibres - that may be suggestive of progressive brain degeneration in response to recurrent seizures. Chronic TLEhs is associated with interrelated DTI-derived and volume-derived brain degenerative abnormalities that are influenced by the duration of the disorder and the side of seizure onset. This work confirms previously contradictory findings by employing multi-modal imaging techniques in parallel in a large sample of patients.

The nuclease hSNM1B/Apollo is linked to the Fanconi anemia pathway via its interaction with FANCP/SLX4.

PubMed

Salewsky, Bastian; Schmiester, Maren; Schindler, Detlev; Digweed, Martin; Demuth, Ilja

2012-11-15

The recessive genetic disorder Fanconi anemia (FA) is clinically characterized by congenital defects, bone marrow failure and an increased incidence of cancer. Cells derived from FA patients exhibit hypersensitivity to DNA interstrand crosslink (ICL)-inducing agents. We have earlier reported a similar cellular phenotype for human cells depleted of hSNM1B/Apollo (siRNA). In fact, hSNM1B/Apollo has a dual role in the DNA damage response and in generation and maintenance of telomeres, the latter function involving interaction with the shelterin protein TRF2. Here we find that ectopically expressed hSNM1B/Apollo co-immunoprecipitates with SLX4, a protein recently identified as a new FA protein, FANCP, and known to interact with several structure-specific nucleases. As shown by immunofluorescence analysis, FANCP/SLX4 depletion (siRNA) resulted in a significant reduction of hSNM1B/Apollo nuclear foci, supporting the functional relevance of this new protein interaction. Interestingly, as an additional consequence of FANCP/SLX4 depletion, we found a reduction of cellular TRF2, in line with its telomere-related function. Finally, analysis of human cells following double knockdown of hSNM1B/Apollo and FANCP/SLX4 indicated that they function epistatically. These findings further substantiate the role of hSNM1B/Apollo in a downstream step of the FA pathway during the repair of DNA ICLs.

Human Fanconi anemia monoubiquitination pathway promotes homologous DNA repair

PubMed Central

Nakanishi, Koji; Yang, Yun-Gui; Pierce, Andrew J.; Taniguchi, Toshiyasu; Digweed, Martin; D'Andrea, Alan D.; Wang, Zhao-Qi; Jasin, Maria

2005-01-01

Fanconi anemia (FA) is a recessive disorder characterized by congenital abnormalities, progressive bone-marrow failure, and cancer susceptibility. Cells from FA patients are hypersensitive to agents that produce DNA crosslinks and, after treatment with these agents, have pronounced chromosome breakage and other cytogenetic abnormalities. Eight FANC genes have been cloned, and the encoded proteins interact in a common cellular pathway. DNA-damaging agents activate the monoubiquitination of FANCD2, resulting in its targeting to nuclear foci that also contain BRCA1 and BRCA2/FANCD1, proteins involved in homology-directed DNA repair. Given the interaction of the FANC proteins with BRCA1 and BRCA2, we tested whether cells from FA patients (groups A, G, and D2) and mouse Fanca–/– cells with a targeted mutation are impaired for this repair pathway. We find that both the upstream (FANCA and FANCG) and downstream (FANCD2) FA pathway components promote homology-directed repair of chromosomal double-strand breaks (DSBs). The FANCD2 monoubiquitination site is critical for normal levels of repair, whereas the ATM phosphorylation site is not. The defect in these cells, however, is mild, differentiating them from BRCA1 and BRCA2 mutant cells. Surprisingly, we provide evidence that these proteins, like BRCA1 but unlike BRCA2, promote a second DSB repair pathway involving homology, i.e., single-strand annealing. These results suggest an early role for the FANC proteins in homologous DSB repair pathway choice. PMID:15650050

Human Fanconi anemia monoubiquitination pathway promotes homologous DNA repair.

PubMed

Nakanishi, Koji; Yang, Yun-Gui; Pierce, Andrew J; Taniguchi, Toshiyasu; Digweed, Martin; D'Andrea, Alan D; Wang, Zhao-Qi; Jasin, Maria

2005-01-25

Fanconi anemia (FA) is a recessive disorder characterized by congenital abnormalities, progressive bone-marrow failure, and cancer susceptibility. Cells from FA patients are hypersensitive to agents that produce DNA crosslinks and, after treatment with these agents, have pronounced chromosome breakage and other cytogenetic abnormalities. Eight FANC genes have been cloned, and the encoded proteins interact in a common cellular pathway. DNA-damaging agents activate the monoubiquitination of FANCD2, resulting in its targeting to nuclear foci that also contain BRCA1 and BRCA2/FANCD1, proteins involved in homology-directed DNA repair. Given the interaction of the FANC proteins with BRCA1 and BRCA2, we tested whether cells from FA patients (groups A, G, and D2) and mouse Fanca-/- cells with a targeted mutation are impaired for this repair pathway. We find that both the upstream (FANCA and FANCG) and downstream (FANCD2) FA pathway components promote homology-directed repair of chromosomal double-strand breaks (DSBs). The FANCD2 monoubiquitination site is critical for normal levels of repair, whereas the ATM phosphorylation site is not. The defect in these cells, however, is mild, differentiating them from BRCA1 and BRCA2 mutant cells. Surprisingly, we provide evidence that these proteins, like BRCA1 but unlike BRCA2, promote a second DSB repair pathway involving homology, i.e., single-strand annealing. These results suggest an early role for the FANC proteins in homologous DSB repair pathway choice.

Taking the fuel out of the fire: evidence for the use of anti-inflammatory agents in the treatment of bipolar disorders.

PubMed

Ayorech, Ziada; Tracy, Derek K; Baumeister, David; Giaroli, Giovanni

2015-03-15

Inflammation has emerged as a potentially important factor - and thus putative pharmacological target - in the pathology of bipolar disorders. However to date no systematic evaluations of the efficacy of add on anti-inflammatory treatment for the depressive and manic episodes have been carried out. Sixteen articles were ultimately identified - by computer searches of databases (including PsycINFO, MEDLINE, and EMBASE), supplemented by hand searches and personal communication - as meeting study inclusion criteria. Anti-manic effects were evaluated in two trials, one of adjunctive n-acetyl cysteine (NAC), one of omega-3 fatty acids (O3FA), and significant improvements only emerged for NAC. Celecoxib had a rapid but short-lived antidepressant effect. Despite limited effects of O3FA on symptoms, imaging data demonstrated alterations in neuronal functioning that might have longer-term therapeutic effects. Evidence was strongest for adjunctive NAC in bipolar depression though conclusions are limited by small sample sizes. Definitive conclusions are limited by the paucity of data, small study sizes, and the variability in methodology used. Current evidence for aspirin or celecoxib is insufficient though further investigation of the potential of celecoxib in early illness onset is warranted. Variable evidence exists for add-on O3FA though an indication of short-term treatment effects on membrane fluidity and neuronal activity suggest longer follow-up assessment is needed. The strongest evidence emerged for NAC in depression and future studies must address the role of illness duration and patients׳ baseline medications on outcomes. Careful consideration of lithium toxicity in the elderly and renal impaired is essential. Copyright © 2014 Elsevier B.V. All rights reserved.

Illumination with 630-nm red light reduces oxidative stress and restores memory by photo-activating catalase and formaldehyde dehydrogenase in SAMP8 mice.

PubMed

Zhang, Jingnan; Yue, Xiangpei; Luo, Hongjun; Jiang, Wenjing; Mei, Yufei; Ai, Li; Gao, Ge; Wu, Yan; Yang, Hui; An, Jieran; Ding, Shumao; Yang, Xu; Sun, Bingui; Luo, Wenhong; He, Rongqiao; Jia, Jianping; Lyu, Jihui; Tong, Zhiqian

2018-06-05

Pharmacological treatments for Alzheimer's disease (AD) have not resulted in desirable clinical efficacy over 100 years. Hydrogen peroxide (H2O2), a reactive and the most stable compound of reactive oxygen species (ROS), contributes to oxidative stress in AD patients. Here, we designed a medical device to emit red light at 630±15 nm from a light-emitting diode (LED-RL) and investigated whether the LED-RL reduces brain H2O2 levels and improves memory in senescence-accelerated prone 8 mouse (SAMP8) model of age-related dementia. We found that age-associated H2O2 directly inhibited formaldehyde dehydrogenase (FDH). FDH inactivity and semicarbazide-sensitive amine oxidase (SSAO) disorder resulted in endogenous formaldehyde (FA) accumulation. Unexpectedly, excess FA, in turn, caused acetylcholine (Ach) deficiency by inhibiting choline acetyltransferase (ChAT) activity in vitro and in vivo. Interestingly, the 630-nm red light can penetrate the skull and abdomen with light penetration rates: ~49% and ~43%, respectively. Illumination with LED-RL markedly activated both catalase and FDH in the brains, cultured cells and purified protein solutions, all reduced brain H2O2 and FA levels and restored brain Ach contents. Consequently, LED-RL not only prevented early-stage memory decline but also rescued late-stage memory deficits in SAMP8 mice. We developed a phototherapeutic device with 630-nm red light, and this LED-RL reduced brain H2O2 levels and reversed age-related memory disorders. The phototherapy of LED-RL has low photo toxicity and high rate of tissue penetration, and non-invasively reverses aging-associated cognitive decline. This finding opens a promising opportunity to translate LED-RL into clinical treatment for patients with dementia.

White Matter Disruptions in Schizophrenia Are Spatially Widespread and Topologically Converge on Brain Network Hubs.

PubMed

Klauser, Paul; Baker, Simon T; Cropley, Vanessa L; Bousman, Chad; Fornito, Alex; Cocchi, Luca; Fullerton, Janice M; Rasser, Paul; Schall, Ulrich; Henskens, Frans; Michie, Patricia T; Loughland, Carmel; Catts, Stanley V; Mowry, Bryan; Weickert, Thomas W; Shannon Weickert, Cynthia; Carr, Vaughan; Lenroot, Rhoshel; Pantelis, Christos; Zalesky, Andrew

2017-03-01

White matter abnormalities associated with schizophrenia have been widely reported, although the consistency of findings across studies is moderate. In this study, neuroimaging was used to investigate white matter pathology and its impact on whole-brain white matter connectivity in one of the largest samples of patients with schizophrenia. Fractional anisotropy (FA) and mean diffusivity (MD) were compared between patients with schizophrenia or schizoaffective disorder (n = 326) and age-matched healthy controls (n = 197). Between-group differences in FA and MD were assessed using voxel-based analysis and permutation testing. Automated whole-brain white matter fiber tracking and the network-based statistic were used to characterize the impact of white matter pathology on the connectome and its rich club. Significant reductions in FA associated with schizophrenia were widespread, encompassing more than 40% (234ml) of cerebral white matter by volume and involving all cerebral lobes. Significant increases in MD were also widespread and distributed similarly. The corpus callosum, cingulum, and thalamic radiations exhibited the most extensive pathology according to effect size. More than 50% of cortico-cortical and cortico-subcortical white matter fiber bundles comprising the connectome were disrupted in schizophrenia. Connections between hub regions comprising the rich club were disproportionately affected. Pathology did not differ between patients with schizophrenia and schizoaffective disorder and was not mediated by medication. In conclusion, although connectivity between cerebral hubs is most extensively disturbed in schizophrenia, white matter pathology is widespread, affecting all cerebral lobes and the cerebellum, leading to disruptions in the majority of the brain's fiber bundles. © The Author 2016. Published by Oxford University Press on behalf of the Maryland Psychiatric Research Center. All rights reserved. For permissions, please email: journals.permissions@oup.com.

Abnormal fronto-parietal white matter organisation in the superior longitudinal fasciculus branches in autism spectrum disorders.

PubMed

Fitzgerald, Jacqueline; Leemans, Alexander; Kehoe, Elizabeth; O'Hanlon, Erik; Gallagher, Louise; McGrath, Jane

2018-03-01

Core features of autism spectrum disorder (ASD) may be underpinned by disrupted functional and structural neural connectivity. Abnormal fronto-parietal functional connectivity has been widely reported in the literature; this may be underpinned by disrupted microstructural organisation of white matter. The superior longitudinal fasciculus (SLF) is a major fronto-parietal white matter tract, the structure of which has been little studied in ASD. The fronto-parietal projections of this tract (SLF I, II and III) are thought to play an important role in a number of cognitive functions including attention and visuospatial processing. To date, the isolation of the fronto-parietal branches of the SLF has been hampered by limitations of traditional tractography approaches. Constrained spherical deconvolution (CSD)-based tractography is an advanced approach that allows valid isolation of the fronto-parietal branches of the SLF. Diffusion MRI data were acquired from 45 participants with ASD and 45 age- and IQ-matched controls. The SLF I, II and III branches were isolated using CSD-based tractography in ExploreDTI. Significantly greater fractional anisotropy (FA) was observed in the right SLF II relative to controls. The ASD group also showed greater linear diffusion coefficient in the left SLF I and the right SLF II. In the SLF II, the ASD group had significantly greater right lateralisation of FA in comparison with the control group. The clinical and functional implications of increased FA in white matter are poorly understood; however, it is possible that this increased white matter organisation in the SLF in ASD may contribute to relative processing advantages in the condition. © 2017 Federation of European Neuroscience Societies and John Wiley & Sons Ltd.

Lower white matter microstructure in the superior longitudinal fasciculus is associated with increased response time variability in adults with attention-deficit/ hyperactivity disorder.

PubMed

Wolfers, Thomas; Onnink, A Marten H; Zwiers, Marcel P; Arias-Vasquez, Alejandro; Hoogman, Martine; Mostert, Jeanette C; Kan, Cornelis C; Slaats-Willemse, Dorine; Buitelaar, Jan K; Franke, Barbara

2015-09-01

Response time variability (RTV) is consistently increased in patients with attention-deficit/hyperactivity disorder (ADHD). A right-hemispheric frontoparietal attention network model has been implicated in these patients. The 3 main connecting fibre tracts in this network, the superior longitudinal fasciculus (SLF), inferior longitudinal fasciculus (ILF) and the cingulum bundle (CB), show microstructural abnormalities in patients with ADHD. We hypothesized that the microstructural integrity of the 3 white matter tracts of this network are associated with ADHD and RTV. We examined RTV in adults with ADHD by modelling the reaction time distribution as an exponentially modified Gaussian (ex-Gaussian) function with the parameters μ, σ and τ, the latter of which has been attributed to lapses of attention. We assessed adults with ADHD and healthy controls using a sustained attention task. Diffusion tensor imaging-derived fractional anisotropy (FA) values were determined to quantify bilateral microstructural integrity of the tracts of interest. We included 100 adults with ADHD and 96 controls in our study. Increased τ was associated with ADHD diagnosis and was linked to symptoms of inattention. An inverse correlation of τ with mean FA was seen in the right SLF of patients with ADHD, but no direct association between the mean FA of the 6 regions of interest with ADHD could be observed. Regions of interest were defined a priori based on the attentional network model for ADHD and thus we might have missed effects in other networks. This study suggests that reduced microstructural integrity of the right SLF is associated with elevated τ in patients with ADHD.

Smoking and the developing brain: altered white matter microstructure in attention-deficit/hyperactivity disorder and healthy controls.

PubMed

van Ewijk, Hanneke; Groenman, Annabeth P; Zwiers, Marcel P; Heslenfeld, Dirk J; Faraone, Stephen V; Hartman, Catharina A; Luman, Marjolein; Greven, Corina U; Hoekstra, Pieter J; Franke, Barbara; Buitelaar, Jan; Oosterlaan, Jaap

2015-03-01

Brain white matter (WM) tracts, playing a vital role in the communication between brain regions, undergo important maturational changes during adolescence and young adulthood, a critical period for the development of nicotine dependence. Attention-deficit/hyperactivity disorder (ADHD) is associated with increased smoking and widespread WM abnormalities, suggesting that the developing ADHD brain might be especially vulnerable to effects of smoking. This study aims to investigate the effect of smoking on (WM) microstructure in adolescents and young adults with and without ADHD. Diffusion tensor imaging was performed in an extensively phenotyped sample of nonsmokers (n = 95, 50.5% ADHD), irregular smokers (n = 41, 58.5% ADHD), and regular smokers (n = 50, 82.5% ADHD), aged 14-24 years. A whole-brain voxelwise approach investigated associations of smoking, ADHD and their interaction, with WM microstructure as measured by fractional anisotropy (FA) and mean diffusivity (MD). Widespread alterations in FA and MD were found for regular smokers compared to irregular and nonsmokers, mainly located in the corpus callosum and WM tracts surrounding the basal ganglia. Several regions overlapped with regions of altered FA for ADHD versus controls, albeit in different directions. Irregular and nonsmokers did not differ, and ADHD and smoking did not interact. Results implicate that smoking and ADHD have independent effects on WM microstructure, and possibly do not share underlying mechanisms. Two mechanisms may play a role in the current results. First, smoking may cause alterations in WM microstructure in the maturing brain. Second, pre-existing WM microstructure differences possibly reflect a risk factor for development of a smoking addiction. © 2014 Wiley Periodicals, Inc.

White matter correlates of impaired attention control in major depressive disorder and healthy volunteers.

PubMed

Rizk, Mina M; Rubin-Falcone, Harry; Keilp, John; Miller, Jeffrey M; Sublette, M Elizabeth; Burke, Ainsley; Oquendo, Maria A; Kamal, Ahmed M; Abdelhameed, Mohamed A; Mann, J John

2017-11-01

Major depressive disorder (MDD) is associated with impaired attention control and alterations in frontal-subcortical connectivity. We hypothesized that attention control as assessed by Stroop task interference depends on white matter integrity in fronto-cingulate regions and assessed this relationship using diffusion tensor imaging (DTI) in MDD and healthy volunteers (HV). DTI images and Stroop task were acquired in 29 unmedicated MDD patients and 16 HVs, aged 18-65 years. The relationship between Stroop interference and fractional anisotropy (FA) was examined using region-of-interest (ROI) and tract-based spatial statistics (TBSS) analyses. ROI analysis revealed that Stroop interference correlated positively with FA in left caudal anterior cingulate cortex (cACC) in HVs (r = 0.62, p = 0.01), but not in MDD (r = -0.05, p= 0.79) even after controlling for depression severity. The left cACC was among 4 ROIs in fronto-cingulate network where FA was lower in MDD relative to HVs (F (1,41) = 8.87, p = 0.005). Additionally, TBSS showed the same group interaction of differences and correlations, although only at a statistical trend level. The modest sample size limits the generalizability of the findings. Structural connectivity of white matter network of cACC correlated with magnitude of Stroop interference in HVs, but not MDD. The cACC-frontal network, sub-serving attention control, may be disrupted in MDD. Less cognitive control may include enhanced effects of salience in HVs, or less effective response inhibition in MDD. Further studies of salience and inhibition components of executive function may better elucidate the relationship between brain white matter changes and executive dysfunction in MDD. Copyright © 2017 Elsevier B.V. All rights reserved.

White Matter Abnormalities in Post-traumatic Stress Disorder Following a Specific Traumatic Event.

PubMed

Li, Lei; Lei, Du; Li, Lingjiang; Huang, Xiaoqi; Suo, Xueling; Xiao, Fenglai; Kuang, Weihong; Li, Jin; Bi, Feng; Lui, Su; Kemp, Graham J; Sweeney, John A; Gong, Qiyong

2016-02-01

Studies of posttraumatic stress disorder (PTSD) are complicated by wide variability in the intensity and duration of prior stressors in patient participants, secondary effects of chronic psychiatric illness, and a variable history of treatment with psychiatric medications. In magnetic resonance imaging (MRI) studies, patient samples have often been small, and they were not often compared to similarly stressed patients without PTSD in order to control for general stress effects. Findings from these studies have been inconsistent. The present study investigated whole-brain microstructural alterations of white matter in a large drug-naive population who survived a specific, severe traumatic event (a major 8.0-magnitude earthquake). Using diffusion tensor imaging (DTI), we explored group differences between 88 PTSD patients and 91 matched traumatized non-PTSD controls in fractional anisotropy (FA), as well as its component elements axial diffusivity (AD) and radial diffusivity (RD), and examined these findings in relation to findings from deterministic DTI tractography. Relations between white matter alterations and psychiatric symptom severity were examined. PTSD patients, relative to similarly stressed controls, showed an FA increase as well as AD and RD changes in the white matter beneath left dorsolateral prefrontal cortex and forceps major. The observation of increased FA in the PTSD group suggests that the pathophysiology of PTSD after a specific acute traumatic event is distinct from what has been reported in patients with several years duration of illness. Alterations in dorsolateral prefrontal cortex may be an important aspect of illness pathophysiology, possibly via the region's established role in fear extinction circuitry. Use-dependent myelination or other secondary compensatory changes in response to heightened demands for threat appraisal and emotion regulation may be involved.

Lower white matter microstructure in the superior longitudinal fasciculus is associated with increased response time variability in adults with attention-deficit/hyperactivity disorder

PubMed Central

Wolfers, Thomas; Onnink, A. Marten H.; Zwiers, Marcel P.; Arias-Vasquez, Alejandro; Hoogman, Martine; Mostert, Jeanette C.; Kan, Cornelis C.; Slaats-Willemse, Dorine; Buitelaar, Jan K.; Franke, Barbara

2015-01-01

Background Response time variability (RTV) is consistently increased in patients with attention-deficit/hyperactivity disorder (ADHD). A right-hemispheric frontoparietal attention network model has been implicated in these patients. The 3 main connecting fibre tracts in this network, the superior longitudinal fasciculus (SLF), inferior longitudinal fasciculus (ILF) and the cingulum bundle (CB), show microstructural abnormalities in patients with ADHD. We hypothesized that the microstructural integrity of the 3 white matter tracts of this network are associated with ADHD and RTV. Methods We examined RTV in adults with ADHD by modelling the reaction time distribution as an exponentially modified Gaussian (ex-Gaussian) function with the parameters μ, σ and τ, the latter of which has been attributed to lapses of attention. We assessed adults with ADHD and healthy controls using a sustained attention task. Diffusion tensor imaging–derived fractional anisotropy (FA) values were determined to quantify bilateral microstructural integrity of the tracts of interest. Results We included 100 adults with ADHD and 96 controls in our study. Increased τ was associated with ADHD diagnosis and was linked to symptoms of inattention. An inverse correlation of τ with mean FA was seen in the right SLF of patients with ADHD, but no direct association between the mean FA of the 6 regions of interest with ADHD could be observed. Limitations Regions of interest were defined a priori based on the attentional network model for ADHD and thus we might have missed effects in other networks. Conclusion This study suggests that reduced microstructural integrity of the right SLF is associated with elevated τ in patients with ADHD. PMID:26079698

White matter microstructure and developmental improvement of hyperactive/impulsive symptoms in attention-deficit/hyperactivity disorder.

PubMed

Francx, Winke; Zwiers, Marcel P; Mennes, Maarten; Oosterlaan, Jaap; Heslenfeld, Dirk; Hoekstra, Pieter J; Hartman, Catharina A; Franke, Barbara; Faraone, Stephen V; O'Dwyer, Laurence; Buitelaar, Jan K

2015-12-01

A developmental improvement of symptoms in attention-deficit/hyperactivity disorder (ADHD) is frequently reported, but the underlying neurobiological substrate has not been identified. The aim of this study was to determine whether white matter microstructure is related to developmental improvement of ADHD symptoms. A cross-sectional magnetic resonance imaging (MRI) analysis was embedded in a prospective follow-up of an adolescent cohort of ADHD and control subjects (NeuroIMAGE). Mean age at baseline was 11.9 years, mean interval of follow-up was 5.9 years. About 75.3% of the original cohort was retained successfully. Data of 101 participants with ADHD combined type at baseline and 40 healthy controls were analysed. ADHD symptoms were measured with semistructured, investigator-based interviews and Conners' questionnaires, on the basis of DSM-IV criteria. Fractional anisotropy (FA) and mean diffusivity (MD) indices of white matter microstructure were measured using whole brain diffusion tensor imaging at follow-up only. In a dimensional analysis FA and MD were related to change in ADHD symptoms. To link this analysis to DSM-IV diagnoses, a post hoc categorical group analysis was conducted comparing participants with persistent (n = 59) versus remittent (n = 42) ADHD and controls. Over time, participants with ADHD showed improvement mainly in hyperactive/impulsive symptoms. This improvement was associated with lower FA and higher MD values in the left corticospinal tract at follow-up. Findings of the dimensional and the categorical analysis strongly converged. Changes in inattentive symptoms over time were minimal and not related to white matter microstructure. The corticospinal tract is important in the control of voluntary movements, suggesting the importance of the motor system in the persistence of hyperactive/impulsive symptoms. © 2015 Association for Child and Adolescent Mental Health.

White matter microstructure and developmental improvement of hyperactive/impulsive symptoms in Attention-Deficit/Hyperactivity Disorder

PubMed Central

Francx, Winke; Zwiers, Marcel P.; Mennes, Maarten; Oosterlaan, Jaap; Heslenfeld, Dirk; Hoekstra, Pieter J.; Hartman, Catharina A.; Franke, Barbara; Faraone, Stephen V.; O’Dwyer, Laurence; Buitelaar, Jan K.

2014-01-01

Background A developmental improvement of symptoms in Attention-Deficit/Hyperactivity Disorder (ADHD) is frequently reported, but the underlying neurobiological substrate has not been identified. The aim of this study was to determine whether white matter microstructure is related to developmental improvement of ADHD symptoms. Methods A cross-sectional Magnetic Resonance Imaging (MRI) analysis was embedded in a prospective follow-up of an adolescent cohort of ADHD and control subjects (NeuroIMAGE). Mean age at baseline was 11.9 years, mean interval of follow-up was 5.9 years. 75.3% of the original cohort was retained successfully. Data of 101 participants with ADHD combined type at baseline and 40 healthy controls was analysed. ADHD symptoms were measured with semi-structured, investigator-based interviews and Conners' questionnaires, on the basis of DSM-IV criteria. Fractional anisotropy (FA) and mean diffusivity (MD) indices of white matter microstructure were measured using whole brain diffusion tensor imaging at follow-up only. In a dimensional analysis FA and MD were related to change in ADHD symptoms. To link this analysis to DSM-IV diagnoses, a post-hoc categorical group analysis was conducted comparing participants with persistent (n=59) versus remittent (n=42) ADHD and controls. Results Over time, participants with ADHD showed improvement mainly in hyperactive/impulsive symptoms. This improvement was associated with lower FA and higher MD values in the left corticospinal tract at follow-up. Findings of the dimensional and the categorical analysis strongly converged. Changes in inattentive symptoms over time were minimal and not related to white matter microstructure. Conclusions The corticospinal tract is important in the control of voluntary movements, suggesting the importance of the motor system in the persistence of hyperactive/impulsive symptoms. PMID:25581343

Effect of combination treatment of S–amlodipine with peroxisome proliferator-activated receptor agonists on metabolic and cardiovascular parameters in Zucker fa/fa rats

PubMed Central

2014-01-01

Background Type 2 diabetes is a complex metabolic disorder characterized by hyperglycemia, impaired glucose tolerance and insulin resistance associated with dyslipidemia and hypertension. The available drugs are not sufficiently efficacious in reducing cardiovascular risk and restoring normal glucose metabolism associated with type 2 diabetes as a mono- or a combination therapy. The present study examined the combined effects of an antihypertensive (S-Amlodipine) and an insulin-sensitizing agent, peroxisome proliferator-activated receptor (PPAR) agonists (Pioglitazone and Ragaglitazar), on cardiovascular risk factors in aged diabetic and insulin-resistant Zucker fa/fa rats. Methods Following combination treatment for 14 days, blood pressure (BP), serum glucose, total cholesterol and triglycerides were measured. Aortic ring study was conducted to determine the effect of combination treatments on phenylephrine-induced vasoconstriction and acetylcholine (Ach)-induced vasorelaxation. Results In combination, S-Amlodipine and Pioglitazone significantly reduced blood glucose (115.1 ± 6.6 vs. 81.7 ± 4.2), BP (184.4 ± 5.0 vs. 155.1 ± 5.0), serum triglycerides (362.5 ± 47.5 vs. 211.1 ± 23.7) and glucose intolerance when compared with vehicle treated Zucker fa/fa rats. Similar results were observed with the combination of S-Amlodipine and Ragaglitazar (Triglycerides, 362.5 ± 47.5 vs. 252.34 ± 27.86; BP, 184.4 ± 5.0 vs. 159.0 ± 8.0) except for serum glucose. ACh-induced vasorelaxation in aortic rings was also superior with both of the combinations compared to individual treatment. Furthermore, there was less body weight gain and food intake with S-Amlodipine and Pioglitazone combination in Zucker fa/fa rats. S-Amlodipine itself caused significant reduction in glucose (115.1 ± 6.6 vs. 89.7 ± 2.7) and BP (184.4 ± 5.0 vs. 156.1 ± 4.0) with improvement in insulin sensitivity observed through oral glucose tolerance test. Conclusions The results suggest that a combination of PPAR agonists and S-Amlodipine has partial benefits in improving the cardiovascular risk factors such as reduction in triglyceride levels, associated with chronic type 2 diabetes, and therefore may be utilized as an approach for addressing some of these devastating metabolic syndrome complications. PMID:24673913

Machining Parameters Optimization using Hybrid Firefly Algorithm and Particle Swarm Optimization

NASA Astrophysics Data System (ADS)

Farahlina Johari, Nur; Zain, Azlan Mohd; Haszlinna Mustaffa, Noorfa; Udin, Amirmudin

2017-09-01

Firefly Algorithm (FA) is a metaheuristic algorithm that is inspired by the flashing behavior of fireflies and the phenomenon of bioluminescent communication and the algorithm is used to optimize the machining parameters (feed rate, depth of cut, and spindle speed) in this research. The algorithm is hybridized with Particle Swarm Optimization (PSO) to discover better solution in exploring the search space. Objective function of previous research is used to optimize the machining parameters in turning operation. The optimal machining cutting parameters estimated by FA that lead to a minimum surface roughness are validated using ANOVA test.

Placental fatty acid transport in maternal obesity.

PubMed

Cetin, I; Parisi, F; Berti, C; Mandò, C; Desoye, G

2012-12-01

Pregestational obesity is a significant risk factor for adverse pregnancy outcomes. Maternal obesity is associated with a specific proinflammatory, endocrine and metabolic phenotype that may lead to higher supply of nutrients to the feto-placental unit and to excessive fetal fat accumulation. In particular, obesity may influence placental fatty acid (FA) transport in several ways, leading to increased diffusion driving force across the placenta, and to altered placental development, size and exchange surface area. Animal models show that maternal obesity is associated with increased expression of specific FA carriers and inflammatory signaling molecules in placental cotyledonary tissue, resulting in enhanced lipid transfer across the placenta, dislipidemia, fat accumulation and possibly altered development in fetuses. Cell culture experiments confirmed that inflammatory molecules, adipokines and FA, all significantly altered in obesity, are important regulators of placental lipid exchange. Expression studies in placentas of obese-diabetic women found a significant increase in FA binding protein-4 expression and in cellular triglyceride content, resulting in increased triglyceride cord blood concentrations. The expression and activity of carriers involved in placental lipid transport are influenced by the endocrine, inflammatory and metabolic milieu of obesity, and further studies are needed to elucidate the strong association between maternal obesity and fetal overgrowth.

High-density defects on PdAg nanowire networks as catalytic hot spots for efficient dehydrogenation of formic acid and reduction of nitrate.

PubMed

Liu, Hu; Yu, Yongsheng; Yang, Weiwei; Lei, Wenjuan; Gao, Manyi; Guo, Shaojun

2017-07-13

Controlling the surface defects of nanocrystals is a new way of tuning/boosting their catalytic properties. Herein, we report networked PdAg nanowires (NWs) with high-density defects as catalytic hot spots for efficient catalytic dehydrogenation of formic acid (FA) and catalytic reduction of nitrates. The networked PdAg NWs exhibit composition-dependent catalytic activity for the dehydrogenation reaction of FA without any additive, with Pd 5 Ag 5 NWs exhibiting the highest activity. They also show good durability, reflected by the retention of their initial activity during the dehydrogenation reaction of FA even after five cycles. Their initial TOF is 419 h -1 at 60 °C in water solution, much higher than those of the most Pd-based catalysts with a support. Moreover, they can efficiently reduce nitrates to alleviate nitrate pollution in water (conversion yield >99%). This strategy opens up a new green synthetic technique to design support-free heterogeneous catalysts with high-density defects as catalytic hot spots for efficient dehydrogenation catalysis of FA to meet the requirement of fuel cell applications and catalytic reduction of nitrates in water polluted with nitrates.

Aeroservoelastic Modeling and Validation of a Thrust-Vectoring F/A-18 Aircraft

NASA Technical Reports Server (NTRS)

Brenner, Martin J.

1996-01-01

An F/A-18 aircraft was modified to perform flight research at high angles of attack (AOA) using thrust vectoring and advanced control law concepts for agility and performance enhancement and to provide a testbed for the computational fluid dynamics community. Aeroservoelastic (ASE) characteristics had changed considerably from the baseline F/A-18 aircraft because of structural and flight control system amendments, so analyses and flight tests were performed to verify structural stability at high AOA. Detailed actuator models that consider the physical, electrical, and mechanical elements of actuation and its installation on the airframe were employed in the analysis to accurately model the coupled dynamics of the airframe, actuators, and control surfaces. This report describes the ASE modeling procedure, ground test validation, flight test clearance, and test data analysis for the reconfigured F/A-18 aircraft. Multivariable ASE stability margins are calculated from flight data and compared to analytical margins. Because this thrust-vectoring configuration uses exhaust vanes to vector the thrust, the modeling issues are nearly identical for modem multi-axis nozzle configurations. This report correlates analysis results with flight test data and makes observations concerning the application of the linear predictions to thrust-vectoring and high-AOA flight.

Assessment of the structural brain network reveals altered connectivity in children with unilateral cerebral palsy due to periventricular white matter lesions

PubMed Central

Pannek, Kerstin; Boyd, Roslyn N.; Fiori, Simona; Guzzetta, Andrea; Rose, Stephen E.

2014-01-01

Background Cerebral palsy (CP) is a term to describe the spectrum of disorders of impaired motor and sensory function caused by a brain lesion occurring early during development. Diffusion MRI and tractography have been shown to be useful in the study of white matter (WM) microstructure in tracts likely to be impacted by the static brain lesion. Aim The purpose of this study was to identify WM pathways with altered connectivity in children with unilateral CP caused by periventricular white matter lesions using a whole-brain connectivity approach. Methods Data of 50 children with unilateral CP caused by periventricular white matter lesions (5–17 years; manual ability classification system [MACS] I = 25/II = 25) and 17 children with typical development (CTD; 7–16 years) were analysed. Structural and High Angular Resolution Diffusion weighted Images (HARDI; 64 directions, b = 3000 s/mm2) were acquired at 3 T. Connectomes were calculated using whole-brain probabilistic tractography in combination with structural parcellation of the cortex and subcortical structures. Connections with altered fractional anisotropy (FA) in children with unilateral CP compared to CTD were identified using network-based statistics (NBS). The relationship between FA and performance of the impaired hand in bimanual tasks (Assisting Hand Assessment—AHA) was assessed in connections that showed significant differences in FA compared to CTD. Results FA was reduced in children with unilateral CP compared to CTD. Seven pathways, including the corticospinal, thalamocortical, and fronto-parietal association pathways were identified simultaneously in children with left and right unilateral CP. There was a positive relationship between performance of the impaired hand in bimanual tasks and FA within the cortico-spinal and thalamo-cortical pathways (r2 = 0.16–0.44; p < 0.05). Conclusion This study shows that network-based analysis of structural connectivity can identify alterations in FA in unilateral CP, and that these alterations in FA are related to clinical function. Application of this connectome-based analysis to investigate alterations in connectivity following treatment may elucidate the neurological correlates of improved functioning due to intervention. PMID:25003031

Development of fisetin-loaded folate functionalized pluronic micelles for breast cancer targeting.

PubMed

Pawar, Atmaram; Singh, Srishti; Rajalakshmi, S; Shaikh, Karimunnisa; Bothiraja, C

2018-01-15

The natural flavonoid fisetin (FS) has shown anticancer properties but its in-vivo administration remains challenging due to its poor aqueous solubility. The aim of the study was to develop FS loaded pluronic127 (PF)-folic acid (FA) conjugated micelles (FS-PF-FA) by the way of increasing solubility, bioavailability and active targetability of FS shall increase its therapeutic efficacy. FA-conjugated PF was prepared by carbodiimide crosslinker chemistry. FS-PF-FA micelles were prepared by thin-film hydration method and evaluated in comparison with free FS and FS loaded PF micelles (FS-PF). The smooth surfaces with spherical in shape of FS-PF-PF micelles displayed smaller in size (103.2 ± 6.1 nm), good encapsulation efficiency (82.50 ± 1.78%), zeta potential (-26.7 ± 0.44 mV) and sustained FS release. Bioavailability of FS from FS-PF-PF micelles was increased by 6-fold with long circulation time, slower plasma elimination and no sign of tissue toxicity as compared to free FS. Further, the FS-PF-FA micelles demonstrated active targeting effect on folate overexpressed human breast cancer MCF-7 cells. The concentration of the drug needed for growth inhibition of 50% of cells in a designed time period (GI50) was 14.3 ± 1.2 µg/ml for FS while it was greatly decreased to 9.8 ± 0.78 µg/ml, i.e. a 31.46% decrease for the FS-PF. Furthermore, the GI50 value for FS-PF-FA was 4.9 ± 0.4 µg/ml, i.e. a 65.737% decrease compared to FS and 50% decrease compare to FS-PF. The results indicate that the FS-PF-FA micelles have the potential to be applied for targeting anticancer drug delivery.

Photocatalytic reduction of nitrate using titanium dioxide for regeneration of ion exchange brine.

PubMed

Yang, Ting; Doudrick, Kyle; Westerhoff, Paul

2013-03-01

Nitrate is often removed from groundwater by ion exchange (IX) before its use as drinking water. Accumulation of nitrate in IX brine reduces the efficiency of IX regeneration and the useful life of the regeneration brine. For the first time, we present a strategy to photocatalytically reduce nitrate in IX brine, thereby extending the use of the brine. Titanium dioxide (Evonik P90), acting as photocatalyst, reduced nitrate effectively in both synthetic brines and sulfate-removed IX brine when formic acid (FA) was used as the hole scavenger (i.e., electron donor) and the initial FA to nitrate molar ratio (IFNR) was 5.6. Increasing the NaCl level in the synthetic brine slowed the nitrate reduction rate without affecting by-product selectivity of ammonium and gaseous N species (e.g., N(2), N(2)O). In a non-modified IX brine, nitrate removal was greatly inhibited owing to the presence of sulfate, which competed with nitrate for active surface sites on P90 and induced aggregation of P90 nanoparticles. After removing sulfate through barium sulfate precipitation, nitrate was effectively reduced; approximately 3.6 × 10(24) photons were required to reduce each mole of nitrate to 83% N Gases and 17% NH(4)(+). To make optimum use of FA and control the residual FA level in treated brine, the IFNR was varied. High IFNRs (e.g., 4, 5.6) were found to be more efficient for nitrate reduction but left higher residual FA in brine. IX column tests were performed to investigate the impact of residual FA for brine reuse. The residual FA in the brine did not significantly affect the nitrate removal capacity of IX resins, and formate contamination of treated water could be eliminated by rinsing with one bed volume of fresh brine. Copyright © 2012 Elsevier Ltd. All rights reserved.

Assembling of stimuli-responsive tumor targeting polypyrrole nanotubes drug carrier system for controlled release.

PubMed

Chen, Jian; Li, Xiufang; Li, Jiawen; Li, Jianbing; Huang, Ling; Ren, Tao; Yang, Xiao; Zhong, Shian

2018-08-01

A stimuli-responsive polypyrrole (PPy) nanotubes drug carrier system has been designed to deliver anticancer drugs to tumor cells in a targeted and controlled manner. The PPy nanotubes drug carrier was fabricated by a template method. The nanotubes surface was functionalized with cleavable acylhydrazone and disulfide bonds by attaching thiolated β-cyclodextrin (β-CD). The solubilizing poly(ethylene glycol) polymer (PEG), attached with an adamantane (Ad) entity at one end and a folate (FA) entity at the other end, was introduced onto the nanotubes surface via β-cyclodextrin-adamantane interaction. The synthesized FA-PEG-Ad-β-CD-PPy showed excellent biocompatibility and low cytotoxicity for two cell lines. Doxorubicin (Dox) loaded FA-PEG-Ad-β-CD-PPy nanotubes showed a triggered in vitro drug release behavior in the presence of acidic media and reducing agents. The folate-mediated endocytosis and intracellular release of Dox-loaded nanoparticles were confirmed by fluorescence microscopy and cell viability evaluations. In the in vitro study, Dox loaded within the nanoparticles showed enhanced selectivity for cancerous cells and reduced cytotoxicity for normal cells compared to free Dox. The PPy based targeted drug vehicle shows excellent promise for drug delivery. Copyright © 2018 Elsevier B.V. All rights reserved.

Response of dissolved trace metals to land use/land cover and their source apportionment using a receptor model in a subtropic river, China.

PubMed

Li, Siyue; Zhang, Quanfa

2011-06-15

Water samples were collected for determination of dissolved trace metals in 56 sampling sites throughout the upper Han River, China. Multivariate statistical analyses including correlation analysis, stepwise multiple linear regression models, and principal component and factor analysis (PCA/FA) were employed to examine the land use influences on trace metals, and a receptor model of factor analysis-multiple linear regression (FA-MLR) was used for source identification/apportionment of anthropogenic heavy metals in the surface water of the River. Our results revealed that land use was an important factor in water metals in the snow melt flow period and land use in the riparian zone was not a better predictor of metals than land use away from the river. Urbanization in a watershed and vegetation along river networks could better explain metals, and agriculture, regardless of its relative location, however slightly explained metal variables in the upper Han River. FA-MLR analysis identified five source types of metals, and mining, fossil fuel combustion, and vehicle exhaust were the dominant pollutions in the surface waters. The results demonstrated great impacts of human activities on metal concentrations in the subtropical river of China. Copyright © 2011 Elsevier B.V. All rights reserved.

Oral Delivery of Nanoparticles Loaded With Ginger Active Compound, 6-Shogaol, Attenuates Ulcerative Colitis and Promotes Wound Healing in a Murine Model of Ulcerative Colitis.

PubMed

Zhang, Mingzhen; Xu, Changlong; Liu, Dandan; Han, Moon Kwon; Wang, Lixin; Merlin, Didier

2018-01-24

Oral drug delivery is the most attractive pathway for ulcerative colitis [UC] therapy, since it has many advantages. However, this strategy has encountered many challenges, including the instability of drugs in the gastrointestinal tract [GT], low targeting of disease tissues, and severe adverse effects. Nanoparticles capable of colitis tissue-targeted delivery and site-specific drug release may offer a unique and therapeutically effective system that addresses these formidable challenges. We used a versatile single-step surface-functionalising technique to prepare PLGA/PLA-PEG-FA nanoparticles loaded with the ginger active compound, 6-shogaol [NPs-PEG-FA/6-shogaol]. The therapeutic efficacy of NPs-PEG-FA/6-shogaol was evaluated in the well-established mouse model of dextran sulphate sodium [DSS]-induced colitis. NPs-PEG-FA exhibited very good biocompatibility both in vitro and in vivo. Subsequent cellular uptake experiments demonstrated that NPs-PEG-FA could undergo efficient receptor-mediated uptake by colon-26 cells and activated Raw 264.7 macrophage cells. In vivo, oral administration of NPs-PEG-FA/6-shogaol encapsulated in a hydrogel system [chitosan/alginate] significantly alleviated colitis symptoms and accelerated colitis wound repair in DSS-treated mice by regulating the expression levels of pro-inflammatory [TNF-α, IL-6, IL-1β, and iNOS] and anti-inflammatory [Nrf-2 and HO-1] factors. Our study demonstrates a convenient, orally administered 6-shogaol drug delivery system that effectively targets colitis tissue, alleviates colitis symptoms, and accelerates colitis wound repair. This system may represent a promising therapeutic approach for treating inflammatory bowel disease [IBD]. Copyright © 2017 European Crohn’s and Colitis Organisation (ECCO). Published by Oxford University Press. All rights reserved. For permissions, please email: journals.permissions@oup.com

Comparative Study of Folic Acid and α-Naphthoflavone on Reducing TCDD-Induced Cleft Palate in Fetal Mice.

PubMed

Yuan, Xingang; He, Xiaomeng; Zhang, Xuan; Liu, Cuiping; Wang, Chen; Qiu, Lin; Pu, Wei; Fu, Yuexian

2017-03-01

  Tocompare the effect of folic acid (FA) and α-naphthoflavone on 2,3,7,8-tetrachlorodibenzo-p-dioxin (TCDD)-induced cleft palate in fetal mice.   Pregnant mice were randomly divided into seven groups. The mice treated with corn oil were used as a negative control. The mice in the other six groups were given a single dose of 28 μg/kg TCDD on GD 10 by gavage. For FA treatment, TCDD-treated mice were also dosed with 5, 10, and 15 mg/kg FA on GD 10, while for α-naphthoflavone treatment, the mice received a single dose of 50 μg/kg or 5 mg/kg α-naphthoflavone on GD 10.   Fetal mice palates were imaged using light and scanning electron microscopy on GD 13.5, GD 14.5, and GD 15.5, and cleft palate were recorded on GD 17.5. The expression of guanosine diphosphate dissociation inhibitor (GDI) in fetal mice palate on GD 15.5 was examined by immunohistochemistry.   TCDD successfully induced cleft palate. Ten mg/ml FA and 5 mg/ml α-naphthoflavone significantly reduced TCDD-induced cleft palate. FA and α-naphthoflavone partly reduced TCDD-induced cleft palate but did not affect the expression of Rho GDI.   FA and α-naphthoflavone may reduce the generation of reactive oxygen species, inhibit MEE apoptosis through anti-oxidation, and increase filopodia and MEE movement. This may result in restoration of the ultrastructure of the palatal surface to a normal state, leading to the fusion and formation of complete palate in TCDD-treated fetal mice.

Novel Nano-Therapeutic Approach Actively Targets Human Ovarian Cancer Stem Cells after Xenograft into Nude Mice.

PubMed

Abou-ElNaga, Amoura; Mutawa, Ghada; El-Sherbiny, Ibrahim M; Abd-ElGhaffar, Hassan; Allam, Ahmed A; Ajarem, Jamaan; Mousa, Shaker A

2017-04-12

The power of tumorigenesis, chemo-resistance and metastasis in malignant ovarian tumors resides in a tiny population of cancer cells known as ovarian cancer stem cells (OCSCs). Developing nano-therapeutic targeting of OCSCs is considered a great challenge. The potential use of poly(lactic-co-glycolic acid) nanoparticles (PLGA NPs) was investigated as a drug delivery system for paclitaxel (PTX) against OCSCs in vitro and in vivo. PTX-loaded PLGA NPs were prepared by an emulsion solvent evaporation method, supported by incorporation of folic acid (FA) as the ligand. NPs were characterized for size, surface morphology, drug loading, and encapsulation efficiency. In vitro cytotoxicity of PTX-loaded FA/PLGA NPs was tested against OCSCs with MTT assay. In vivo anti-tumoral efficiency and active targeting potential of prepared NPs against tumors in nude mice were investigated. In vitro results revealed that IC 50 of PTX was significantly reduced after loading on PLGA NPs. On the other hand, in vivo results showed that PLGA NPs enhanced the tumor suppression efficiency of PTX. Investigation with real time quantitative PCR analysis revealed the limiting expression of chemo-resistant genes ( ABCG2 and MDR1 ) after applying PLGA NPs as a drug delivery system for PTX. Histopathological examination of tumors showed the effective biological influence of PTX-loaded FA/PLGA NPs through the appearance of reactive lymphoid follicles. Targeting potential of PTX was activated by FA/PLGA NPs through significant preservation of body weight ( p < 0.0001) and minimizing the systemic toxicity in healthy tissues. Immunohistochemical investigation revealed a high expression of apoptotic markers in tumor tissue, supporting the targeting effect of FA/PLGA NPs. A drug delivery system based on FA/PLGA NPs can enhance PTX's in vitro cytotoxicity and in vivo targeting potential against OCSCs.

Simultaneous detection of folic acid and methotrexate by an optical sensor based on molecularly imprinted polymers on dual-color CdTe quantum dots.

PubMed

Ensafi, Ali A; Nasr-Esfahani, Parisa; Rezaei, B

2017-12-15

In this work, molecularly imprinted polymers (MIPs) were used on the surface of cadmium telluride quantum dots (CdTe QDs) for the simultaneous determination of folic acid (FA) and methotrexate (MTX). For this purpose, two different sizes of CdTe QDs with emission peaks in the yellow (QD Y ) and orange (QD O ) spectral regions were initially synthesized and capped with MIPs. FA and MTX were used as templates for the synthesis of the two composites and designated as QD Y -MIPs and QD O -MIPs, respectively. Fourier transform infrared spectroscopy, transmission electron microscopy, and fluorescence spectroscopy were employed to characterize the composites. QD Y -MIPs and QD O -MIPs were then mixed (to form QDs-MIPs) and excited at identical excitation wavelengths; they emitted two different emission wavelengths without any spectral overlap. The fluorescence signals of QD Y -MIPs and QD O -MIPs diminished in intensity with increasing concentration of the corresponding template molecules. Under optimal conditions, the dynamic range was 0.5-20 μmol L -1 for FA and MTX, and the detection limits for FA and MTX were 32.0 nmol L -1 and 34.0 nmol L -1 , respectively. The reproducibility of the method was checked for 12.5 μmol L -1 of FA and MTX to find RSD values of 4.2% and 6.3%, respectively. Finally, the applicability of the method was checked using human blood plasma samples. Results indicated the successful application of the method as a fluorescent probe for the rapid and simultaneous detection of FA and MTX in real samples. Copyright © 2017 Elsevier B.V. All rights reserved.

Low-dose developmental bisphenol A exposure alters fatty acid metabolism in Fischer 344 rat offspring.

PubMed

Dunder, Linda; Halin Lejonklou, Margareta; Lind, Lars; Risérus, Ulf; Lind, P Monica

2018-06-06

Bisphenol A (BPA) is an endocrine disruptor and also a suggested obesogen and metabolism-disrupting chemical. Accumulating data indicates that the fatty acid (FA) profile and their ratios in plasma and other metabolic tissues are associated with metabolic disorders. Stearoyl-CoA desaturase 1 (SCD-1) is a key regulator of lipid metabolism and its activity can be estimated by dividing the FA product by its precursor measured in blood or other tissues. The primary aim of this study was to investigate the effect of low-dose developmental BPA exposure on tissue-specific FA composition including estimated SCD-1 activity, studied in 5- and 52-week (wk)-old Fischer 344 (F344) rat offspring. Pregnant F344 rats were exposed to BPA via their drinking water corresponding to 0: [CTRL], 0.5: [BPA0.5], or 50 µg/kg BW/day: [BPA50], from gestational day 3.5 until postnatal day 22. BPA0.5 increased SCD-16 (estimated as the 16:1n-7/16:0 ratio) and SCD-18 (estimated as the 18:1n-9/18:0 ratio) indices in inguinal white adipose tissue triglycerides (iWAT-TG) and in plasma cholesterol esters (PL-CE), respectively, in 5-wk-old male offspring. In addition, BPA0.5 altered the FA composition in male offspring, e.g. by decreasing levels of the essential polyunsaturated FA linoleic acid (18:2n-6) in iWAT-and liver-TG. No differences were observed regarding the studied FAs in 52-wk-old offspring, although a slightly increased BW was observed in 52-wk-old female offspring. Low-dose developmental BPA exposure increased SCD-16 in iWAT-TG and SCD-18 in PL-CE of male offspring, which may reflect higher SCD-1 activity in these tissues. Altered desaturation activity and signs of altered FA composition are novel findings that may indicate insulin resistance in the rat offspring. These aforementioned results, together with the observed increased BW, adds to previously published data demonstrating that BPA can act as a metabolism disrupting chemical. Copyright © 2018 The Authors. Published by Elsevier Inc. All rights reserved.

Poly(ferulic acid-co-tyrosine): Effect of the Regiochemistry on the Photophysical and Physical Properties en Route to Biomedical Applications

PubMed Central

2015-01-01

The photophysical and mechanical properties of novel poly(carbonate-amide)s derived from two biorenewable resources, ferulic acid (FA) and l-tyrosine ethyl ester, were evaluated in detail. From these two bio-based precursors, a series of four monomers were generated (having amide and/or carbonate coupling units with remaining functionalities to allow for carbonate formation) and transformed to a series of four poly(carbonate-amide)s. The simplest monomer, which was biphenolic and was obtained in a single amidation synthetic step, displayed bright, visible fluorescence that was twice brighter than FA. Multidimensional fluorescence spectroscopy of the polymers in solution highlighted the strong influence that regioselectivity and the degree of polymerization have on their photophysical properties. The regiochemistry of the system had little effect on the wettability, surface free energy, and Young’s modulus (ca. 2.5 GPa) in the solid state. Confocal imaging of solvent-cast films of each polymer revealed microscopically flat surfaces with fluorescent emission deep into the visible region. Fortuitously, one of the two regiorandom polymers (obtainable from the biphenolic monomer in only an overall two synthetic steps from FA and l-tyrosine ethyl ester) displayed the most promising fluorescent properties both in the solid state and in solution, allowing for the possibility of translating this system as a self-reporting or imaging agent in future applications. To further evaluate the potential of this polymer as a biodegradable material, hydrolytic degradation studies at different pH values and temperatures were investigated. Additionally, the antioxidant properties of the degradation products of this polymer were compared with its biphenolic monomer and FA. PMID:25364040

Nanoassemblies from amphiphilic cytarabine prodrug for leukemia targeted therapy.

PubMed

Liu, Jing; Zhao, Dujuan; He, Wenxiu; Zhang, Huiyuan; Li, Zhonghao; Luan, Yuxia

2017-02-01

The anti-leukemia effect of cytarabine (Ara-C) is severely restricted by its high hydrophilic properties and rapid plasma degradation. Herein, a novel amphiphilic small molecular prodrug of Ara-C was developed by coupling a short aliphatic chain, hexanoic acid (HA) to 4-NH 2 of the parent drug. Based on the amphiphilic nature, the resulting bioconjugate (HA-Ara) could spontaneously self-assemble into stable spherical nanoassemblies (NAs) with an extremely high drug loading (∼71wt%). Moreover, folate receptor (FR)-targeting NAs with high grafting efficient folic acid - bovine serum albumin (FA-BSA) conjugate immobilized on the surface (NAs/FA-BSA) was prepared. The results of MTT assays on FR-positive K562 cells and FR-negative A549 cells demonstrated higher cytotoxicity of HA-Ara NAs than the native drug. Especially, the IC 50 values revealed that NAs/FA-BSA was 3 and 2-fold effective than non-targeted NAs after 24 and 48h treatment with K562 cells, respectively indicating FR-mediated enhanced anti-tumor efficacy. In vitro cellular uptake, larger accumulation of HA-Ara NAs were observed in comparative with the free FITC and the results further confirmed the selective uptake of NAs/FA-BSA in folate receptor enriched cancer cells. Above all, self-assembled HA-Ara NAs exhibited potential superiority for Ara-C delivery and FA-modified NAs would be an excellent candidate for targeting leukemia therapy. Copyright © 2016 Elsevier Inc. All rights reserved.

Microstructure and wear characterization of aluminum matrix composites reinforced with industrial waste fly ash particulates synthesized by friction stir processing

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

Dinaharan, I., E-mail: dinaweld2009@gmail.com

Fly ash (FA) is a waste product of coal combustion in thermal power plants which is available in massive quantities all over the world causing land pollution. This paper reports the characterization of AA6061 aluminum matrix composites (AMCs) reinforced with FA particles synthesized using friction stir processing (FSP). The volume fraction of FA particles was varied from 0 to 18 in steps of 6. The prepared AMCs were characterized using optical microscopy (OM), scanning electron microscopy (SEM) and electron backscattered diagram (EBSD). The wear rate was estimated using a pin-on-disc wear apparatus. FA particles were observed to be distributed homogeneouslymore » in the AMC irrespective of the location within the stir zone. The EBSD micrographs revealed remarkable grain refinement in the AMC. The incorporation of FA particles enhanced the microhardness and wear resistance of the AMC. The strengthening mechanisms of the AMC were discussed and correlated to the observed microstructures. The wear mechanisms were identified by characterizing the wear debris and worn surfaces. - Highlights: •Industrial waste fly ash was used to produce aluminum matrix composites. •Friction stir processing was used to produce AA6061/Fly Ash composite. •Fly ash particles refined the grains of aluminum matrix. •Fly ash particles enhanced the hardness and wear resistance. •Successful utilization of fly ash to make aluminum composites reduces land pollution.« less

Wind Tunnel Visualization of the Flow Over a Full-Scale F/A-18 Aircraft

NASA Technical Reports Server (NTRS)

Lanser, Wendy R.; Botha, Gavin J.; James, Kevin D.; Crowder, James P.; Schmitz, Fredric H. (Technical Monitor)

1994-01-01

The proposed paper presents flow visualization performed during experiments conducted on a full-scale F/A-18 aircraft in the 80- by 120-Foot Wind-Tunnel at NASA Ames Research Center. This investigation used both surface and off-surface flow visualization techniques to examine the flow field on the forebody, canopy, leading edge extensions (LEXs), and wings. The various techniques used to visualize the flow field were fluorescent tufts, flow cones treated with reflective material, smoke in combination with a laser light sheet, and a video imaging system. The flow visualization experiments were conducted over an angle of attack range from 20deg to 45deg and over a sideslip range from -10deg to 10deg. The results show regions of attached and separated flow on the forebody, canopy, and wings. Additionally, the vortical flow is clearly visible over the leading-edge extensions, canopy, and wings.

Structure-Property-Environmental Relations in Glass and Glass-Ceramics.

DTIC Science & Technology

1980-03-01

dense Al203 result in a deep surface layer of preferred orientation detection by RKS methods. ii: C Mv CL.ASSIFICAIC S . e .. fa " " p h D e TABLE OF...distribution and decreases the isoelectric point of the powders. Variations in processing of dense Al 203 result in a deep surface layer of preferred...by their surfaces, it is essential that we learn how to predict the surface chemistry of these materials in order to optimize their performance. The

Comparative adsorption of Eu(III) and Am(III) on TPD.

PubMed

Fan, Q H; Zhao, X L; Ma, X X; Yang, Y B; Wu, W S; Zheng, G D; Wang, D L

2015-09-01

Comparative adsorption behaviors of Eu(III) and Am(III) on thorium phosphate diphosphate (TPD), i.e., Th4(PO4)4P2O7, have been studied using a batch approach and surface complexation model (SCM) in this study. The results showed that Eu(III) and Am(III) adsorption increased to a large extent with the increase in TPD dose. Strong pH-dependence was observed in both Eu(III) and Am(III) adsorption processes, suggesting that inner-sphere complexes (ISCs) were possibly responsible for the adsorption of Eu(III) and Am(III). Meanwhile, the adsorption of Eu(III) and Am(III) decreased to a different extent with the increase in ion strength, which was possibly related to outer-sphere complexes and/or ion exchange. In the presence of fulvic acid (FA), the adsorption of Eu(III) and Am(III) showed high enhancement mainly due to the ternary surface complexes of TPD-FA-Eu(3+) and TPD-FA-Am(3+). The SCM showed that one ion exchange (≡S3Am/Eu) and two ISCs (≡(XO)2Am/EuNO3 and ≡(YO)2Am/EuNO3) seemed more reasonable to quantitatively describe the adsorption edges of both Eu(III) and Am(III). Our findings obviously showed that Eu(III) could be a good analogue to study actinide behaviors in practical terms. However, it should be kept in mind that there are still obvious differences between the characteristics of Eu(III) and Am(III) in some special cases, for instance, the complex ability with organic matter and adsorption affinity to a solid surface.

Integrity of the corpus callosum in patients with periventricular nodular heterotopia related epilepsy by FLNA mutation.

PubMed

Liu, Wenyu; An, Dongmei; Niu, Running; Gong, Qiyong; Zhou, Dong

2018-01-01

To investigate the quantitative diffusion properties of the corpus callosum (CC) in a large group of patients with periventricular nodular heterotopia (PNH) related epilepsy and to further investigate the effect of Filamin A ( FLNA ) mutation on these properties. Patients with PNH (n = 34), subdivided into FLNA -mutated (n = 11) and FLNA -nonmutated patients (n = 23) and healthy controls (n = 34), underwent 3.0 T structural MRI and diffusion imaging scan (64 direction). Fractional anisotropy (FA) and mean diffusivity (MD) were measured in the three major subdivisions of the CC (genu, body and splenium). Correlations between DTI metric changes and clinical parameters were also evaluated. Furthermore, the effect of FLNA mutation on structural integrity of the corpus callosum was examined. Patients with PNH and epilepsy had significant reductions in FA for the genu and splenium of the CC, accompanied by increases in MD for the splenium, as compared to healthy controls. There were no correlations between clinical parameters of epilepsy and MD. The FA value in the splenium negatively correlated with epilepsy duration. Interestingly, FLNA -mutated patients showed significantly decreased FA for all three major subdivisions of the CC, and increased MD for the genu and splenium, as compared to HCs and FLNA -nonmutated patients. These findings support the conclusion that patients with epilepsy secondary to PNH present widespread microstructural changes found in the corpus callosum that extend beyond the macroscopic MRI-visible lesions. This study also indicates that FLNA may affect white matter integrity in this disorder.

Zebrafish retinal defects induced by ethanol exposure are rescued by retinoic acid and folic acid supplement

PubMed Central

Muralidharan, Pooja; Sarmah, Swapnalee; Marrs, James A.

2014-01-01

Fetal Alcohol Spectrum Disorder (FASD) is caused by prenatal alcohol exposure, producing craniofacial, sensory, motor, and cognitive defects. FASD is highly prevalent in low socioeconomic populations, which are frequently accompanied by malnutrition. FASD-associated ocular pathologies include microphthalmia, optic nerve hypoplasia, and cataracts. The present study characterizes specific retinal tissue defects, identifies ethanol-sensitive stages during retinal development, and dissects the effect of nutrient supplements, such as retinoic acid (RA) and folic acid (FA) on ethanol-induced retinal defects. Exposure to pathophysiological concentrations of ethanol (during midblastula transition through somitogenesis; 2–24 hours post fertilization [hpf]) altered critical transcription factor expression involved in retinal cell differentiation, and produced severe retinal ganglion cell, photoreceptor, and Müller glial differentiation defects. Ethanol exposure did not alter retinal cell differentiation induction, but increased retinal cell death and proliferation. RA and FA nutrient co-supplementation rescued retinal photoreceptor and ganglion cell differentiation defects. Ethanol exposure during retinal morphogenesis stages (16–24 hpf) produced retinal defects like those seen with ethanol exposure between 2–24 hpf. Significantly, during an ethanol-sensitive time window (16–24 hpf), RA co-supplementation moderately rescued these defects, whereas FA co-supplementation showed significant rescue of optic nerve and photoreceptor differentiation defects. Interestingly, RA, but not FA, supplementation after ethanol exposure could reverse ethanol-induced optic nerve and photoreceptor differentiation defects. Our results indicate that various ethanol-sensitive events underlie FASD-associated retinal defects. Nutrient supplements like retinoids and folate were effective in alleviating ethanol-induced retinal defects. PMID:25541501

Affective traits of psychopathy are linked to white-matter abnormalities in impulsive male offenders.

PubMed

Vermeij, Anouk; Kempes, Maaike M; Cima, Maaike J; Mars, Rogier B; Brazil, Inti A

2018-04-26

Psychopathy is a personality disorder typified by lack of empathy and impulsive antisocial behavior. Psychopathic traits may partly relate to disrupted connections between brain regions. The aim of the present study was to link abnormalities in microstructural integrity of white-matter tracts to the severity of different psychopathic traits in 15 male offenders with impulse control problems and 10 without impulse control problems. Psychopathic traits were assessed using the Psychopathy Checklist-revised (PCL-R). Diffusion-weighted MRI was used to examine white-matter tracts. Fractional anisotropy (FA), an index of white-matter integrity, was calculated for each voxel. Clusters of voxels showing a significant relationship with psychopathy severity were submitted to probabilistic tractography. No significant correlations between psychopathy severity and FA were present in the whole group of impulsive and nonimpulsive offenders. In impulsive offenders, interpersonal-affective traits (PCL-R Factor 1) were negatively correlated with FA in the anterior and posterior temporal lobe and orbitofrontal area. Further analyses indicated that elevated affective traits (PCL-R Facet 2) were specifically related to reduced FA in the right temporal lobe. Our findings suggest that white-matter abnormalities in temporal and frontotemporal tracts may be linked to the interpersonal-affective deficits of psychopathy in offenders with relatively severe impulse control problems. Our study offers novel insights into the relationships between the four facets of psychopathy and disrupted structural connectivity, and may provide new leads for further characterization of different subtypes of antisocial populations. (PsycINFO Database Record (c) 2018 APA, all rights reserved).

Zebrafish retinal defects induced by ethanol exposure are rescued by retinoic acid and folic acid supplement.

PubMed

Muralidharan, Pooja; Sarmah, Swapnalee; Marrs, James A

2015-03-01

Fetal Alcohol Spectrum Disorder (FASD) is caused by prenatal alcohol exposure, producing craniofacial, sensory, motor, and cognitive defects. FASD is highly prevalent in low socioeconomic populations, which are frequently accompanied by malnutrition. FASD-associated ocular pathologies include microphthalmia, optic nerve hypoplasia, and cataracts. The present study characterizes specific retinal tissue defects, identifies ethanol-sensitive stages during retinal development, and dissects the effect of nutrient supplements, such as retinoic acid (RA) and folic acid (FA) on ethanol-induced retinal defects. Exposure to pathophysiological concentrations of ethanol (during midblastula transition through somitogenesis; 2-24 h post fertilization [hpf]) altered critical transcription factor expression involved in retinal cell differentiation, and produced severe retinal ganglion cell, photoreceptor, and Müller glial differentiation defects. Ethanol exposure did not alter retinal cell differentiation induction, but increased retinal cell death and proliferation. RA and FA nutrient co-supplementation rescued retinal photoreceptor and ganglion cell differentiation defects. Ethanol exposure during retinal morphogenesis stages (16-24 hpf) produced retinal defects like those seen with ethanol exposure between 2 and 24 hpf. Significantly, during an ethanol-sensitive time window (16-24 hpf), RA co-supplementation moderately rescued these defects, whereas FA co-supplementation showed significant rescue of optic nerve and photoreceptor differentiation defects. Interestingly, RA, but not FA, supplementation after ethanol exposure could reverse ethanol-induced optic nerve and photoreceptor differentiation defects. Our results indicate that various ethanol-sensitive events underlie FASD-associated retinal defects. Nutrient supplements like retinoids and folate were effective in alleviating ethanol-induced retinal defects. Copyright © 2015 Elsevier Inc. All rights reserved.

Serum fatty acid profile in psoriasis and its comorbidity.

PubMed

Myśliwiec, Hanna; Baran, Anna; Harasim-Symbor, Ewa; Myśliwiec, Piotr; Milewska, Anna Justyna; Chabowski, Adrian; Flisiak, Iwona

2017-07-01

Psoriasis is a chronic inflammatory skin disease that is accompanied by metabolic disturbances and cardio-metabolic disorders. Fatty acids (FAs) might be a link between psoriasis and its comorbidity. The aim of the study was to evaluate serum concentrations of FAs and to investigate their association with the disease activity, markers of inflammation and possible involvement in psoriatic comorbidity: obesity, type 2 diabetes and hypertension. We measured 14 total serum fatty acids content and composition by gas-liquid chromatography and flame-ionization detector after direct in situ transesterification in 85 patients with exacerbated plaque psoriasis and in 32 healthy controls. FAs were grouped according to their biologic properties to saturated FA (SFA), unsaturated FA (UFA), monounsaturated FA (MUFA), n-3 polyunsaturated FA (n-3 PUFA) and n-6 PUFA. Generally, patients characteristic included: Psoriasis Area and Severity Index (PASI), Body Mass Index, inflammatory and biochemical markers, lipid profile and presence of psoriatic comorbidity. We have observed highly abnormal FAs pattern in psoriatic patients both with and without obesity compared to the control group. We have demonstrated association of PASI with low levels of circulating DHA, n-3 PUFA (p = 0.044 and p = 0.048, respectively) and high percent of MUFA (p = 0.024) in the non-obese psoriatic group. The SFA/UFA ratio increased with the duration of the disease (p = 0.03) in all psoriatic patients. These findings indicate abnormal FAs profile in psoriasis which may reflect metabolic disturbances and might play a role in the psoriatic comorbidity.

Food allergy: Children's symptom levels are associated with mothers' psycho-socio-economic variables.

PubMed

Cortes, Aaron; Castillo, Angela; Sciaraffia, Alicia

2018-01-01

Allergies affect children's health as well as their quality of life, stress levels, and family budget. The available literature suggests that family, social and psychological factors are affected by allergic pathologies such as rhinitis, asthma and atopic dermatitis. However, few studies have focused on quantifying such association in child food allergy. This study aims to enhance the understanding of the associations between caregiver variables and children's Food Allergy (FA). The study involved 206 participants: 103 mothers plus 103 children with IgE mediated FA. The analyses excluded two outliers comprising 101 subjects. For statistical analyses, each dyad -mother/child- was considered to be one subject unity. A between-subjects one-way ANOVA determined the association of children's cutaneous, gastric and respiratory symptoms with anxiety, depression, perceived social support and socioeconomic factors in the mothers. There are significant associations between children's allergic symptoms (gastric and cutaneous) and mothers' psychological state (anxiety and depression); family budget; social interactions (with friends, family and partner); understanding of health care required by their child; and sleep disorders. Respiratory symptoms did not show any significant associations with the dependent variables. FA is a process in which children's symptoms are significantly associated with socioeconomic and psychological variables of the mothers. The presence or absence of some specific symptoms is directly associated with specific impacts on the mothers. An understanding of such dynamics supports the consideration of a comprehensive and multidisciplinary therapeutic approach to offer more ecological healthcare for "families living with FA." Copyright © 2017 Elsevier Inc. All rights reserved.

Concomitant Fractional Anisotropy and Volumetric Abnormalities in Temporal Lobe Epilepsy: Cross-Sectional Evidence for Progressive Neurologic Injury

PubMed Central

Gerdes, Jan S.; Weber, Bernd; Deppe, Michael

2012-01-01

Background In patients with temporal lobe epilepsy and associated hippocampal sclerosis (TLEhs) there are brain abnormalities extending beyond the presumed epileptogenic zone as revealed separately in conventional magnetic resonance imaging (MRI) and MR diffusion tensor imaging (DTI) studies. However, little is known about the relation between macroscopic atrophy (revealed by volumetric MRI) and microstructural degeneration (inferred by DTI). Methodology/Principal Findings For 62 patients with unilateral TLEhs and 68 healthy controls, we determined volumes and mean fractional anisotropy (FA) of ipsilateral and contralateral brain structures from T1-weighted and DTI data, respectively. We report significant volume atrophy and FA alterations of temporal lobe, subcortical and callosal regions, which were more diffuse and bilateral in patients with left TLEhs relative to right TLEhs. We observed significant relationships between volume loss and mean FA, particularly of the thalamus and putamen bilaterally. When corrected for age, duration of epilepsy was significantly correlated with FA loss of an anatomically plausible route - including ipsilateral parahippocampal gyrus and temporal lobe white matter, the thalamus bilaterally, and posterior regions of the corpus callosum that contain temporal lobe fibres - that may be suggestive of progressive brain degeneration in response to recurrent seizures. Conclusions/Significance Chronic TLEhs is associated with interrelated DTI-derived and volume-derived brain degenerative abnormalities that are influenced by the duration of the disorder and the side of seizure onset. This work confirms previously contradictory findings by employing multi-modal imaging techniques in parallel in a large sample of patients. PMID:23071638

Neuroticism is linked to microstructural left-right asymmetry of fronto-limbic fibre tracts in adolescents with opposite effects in boys and girls.

PubMed

Madsen, Kathrine Skak; Jernigan, Terry L; Vestergaard, Martin; Mortensen, Erik Lykke; Baaré, William F C

2018-06-01

Neuroticism is a fundamental personality trait that reflects a tendency to experience heightened negative affect and susceptibility to stress. Negative emotionality has been associated with fronto-limbic brain structures and connecting fibre tracts. The major fibre tracts connecting the frontal and limbic brain regions are the cingulum bundle and uncinate fasciculus. We previously found that healthy adults with higher neuroticism scores had decreased left relative to right fractional anisotropy (FA) of the cingulum. Both cingulum and uncinate fasciculus FA increases throughout childhood and into early adulthood. Since adolescence is associated with an increased incidence of anxiety and mood disorders, for which neuroticism is a known risk factor, the question arises whether the association between neuroticism and fronto-limbic white matter microstructure asymmetry is already present in children and adolescents or whether such relationship emerges during this age period. To address this question, we assessed 72 typically-developing 10-to-15 year-olds with diffusion-weighted imaging on a 3 T magnetic resonance scanner. Neuroticism was assessed with the Junior Eysenck Personality Questionnaire. FA and parallel and perpendicular diffusivity measures were extracted for cingulum, uncinate fasciculus as well as the white matter underlying the ventromedial prefrontal cortex. Higher neuroticism scores were associated with decreased left relative to right cingulum FA in boys, while in girls, higher neuroticism scores were associated with increased left relative to right cingulum and ventromedial prefrontal white matter FA, indicating that there are sex differences in the neural correlates of neuroticism. Our findings suggest that the link between neuroticism and frontal-limbic white matter microstructure asymmetry likely predates early adolescence. Future studies need to elucidate the significance of the observed sex differences in the neural correlates of neuroticism. Copyright © 2018 The Authors. Published by Elsevier Ltd.. All rights reserved.

The 5-HTTLPR and BDNF polymorphisms moderate the association between uncinate fasciculus connectivity and antidepressants treatment response in major depression.

PubMed

Tatham, Erica L; Hall, Geoff B C; Clark, Darren; Foster, Jane; Ramasubbu, Rajamannar

2017-03-01

Symptom improvement in depression due to antidepressant treatment is highly variable and clinically unpredictable. Linking neuronal connectivity and genetic risk factors in predicting antidepressant response has clinical implications. Our investigation assessed whether indices of white matter integrity, serotonin transporter-linked polymorphism (5-HTTLPR) and brain-derived neurotrophic factor (BDNF) val66met polymorphism predicted magnitude of depression symptom change following antidepressant treatment. Fractional anisotropy (FA) was used as an indicator of white matter integrity and was assessed in the uncinate fasciculus and superior longitudinal fasciculus using tract-based spatial statistics (TBSS) and probabilistic tractography. Forty-six medication-free patients with major depressive disorder participated in a diffusion tensor imaging scan prior to completing an 8-week treatment regime with citalopram or quetiapine XR. Indexed improvements in Hamilton Depression Rating Scale score from baseline to 8-week endpoint were used as an indicator of depression improvement. Carriers of the BDNF met allele exhibited lower FA values in the left uncinate fasciculus relative to val/val individuals [F(1, 40) = 7.314, p = 0.009]. Probabilistic tractography identified that higher FA in the left uncinate fasciculus predicted percent change in depression severity, with BDNF moderating this association [F(3, 30) = 3.923, p = 0.018]. An interaction between FA in the right uncinate fasciculus and 5-HTTLPR also predicted percent change in depression severity [F(5, 25) = 5.315, p = 0.002]. Uncorrected TBSS results revealed significantly higher FA in hippocampal portions of the cingulum bundle in responders compared to non-responders (p = 0.016). The predictive value of prefrontal and amygdala/hippocampal WM connectivity on antidepressant treatment response may be influenced by 5-HTTLPR and BDNF polymorphisms in MDD.

Migraine in young females with irritable bowel syndrome: still a challenge

PubMed Central

Georgescu, Doina; Reisz, Daniela; Gurban, Camelia Vidita; Georgescu, Liviu Andrei; Ionita, Ioana; Ancusa, Oana Elena; Lighezan, Daniel

2018-01-01

Migraine without aura is frequently reported in female patients with irritable bowel syndrome (IBS), but knowledge about the relationship between these two conditions is still lacking. This study was aimed to explore the particularities of migraine without aura in young female patients with IBS in order to establish a possible link between them. From a cohort of young female patients hospitalized with IBS in the Internal Medicine Department, 30 joined this pilot study, and they were assigned into two groups on the basis of presence or absence of migraine. In this sample, 15 patients have mild to moderate migraine without aura, with a recently taken normal brain scan, and 15 were without migraine. Diseases and conditions not related to migraine and other possible specific female comorbidities were ruled out. Patients undertook a thorough clinical examination in order to assess fibromyalgia (FM) and chronic pelvic pain (CPP), Questionnaires for migraine disability assessment (MIDAS) and generalized anxiety disorder (GAD) were performed. Laboratory testing of blood, urine, and stool were also performed. Optimized lymphocyte proliferation test for food allergy (FA) and a fecal microbiota (microbiological semiquantitative method) for dysbiosis (DB) assessment were performed. Based on the results, migraine-positive group displayed more severe comorbidities: FM (p=0.0002), FA (p=0.0006), CPP (p=0.026), higher scores of anxiety (GAD, p=0.0008), and more severe DB (p=0.0009). We noticed a strong positive correlation between MIDAS and GAD (r=0.83), a good positive correlation between MIDAS and DB (r=0.56), and a moderate positive correlation between MIDAS, FM, and FA (r=0.46 and 0.41). In conclusion, young female patients with IBS and migraine without aura displayed more severe associated issues – anxiety, intestinal DB, FM, FA, and CPP. The severity of migraine correlated well with anxiety range and DB magnitude and moderately with FM and FA. PMID:29302188

[Clinical-demographic factors associated with fear-avoidance in subjects with non-specific chronic low back pain in Primary Care: secondary analysis of intervention study].

PubMed

Díaz-Cerrillo, Juan Luis; Rondón-Ramos, Antonio; Clavero-Cano, Susana; Pérez-González, Rita; Martinez-Calderon, Javier; Luque-Suarez, Alejandro

2018-01-30

To describe some sociodemographics and clinical characteristics of subjects with Non-specific Chronic Low Back Pain (NCLBP) in Primary Care, as well as to investigate their association with Fear-Avoidance (FA). Cross-sectional. Secondary analysis of an intervention study. Basic Health Areas in Costa del Sol Health District (Málaga, Spain). An analysis was performed on 147 subjects with NCLBP from a previous intervention study database in Primary Care Physiotherapy (PCP). Characteristics: age 18-65; understanding of the Spanish language; absence of cognitive disorders, fibromyalgia or dorsolumbar surgery, and to be able to perform physical exercise. The main variable was FA level (FABQ and the FABQ-PA and FABQ-W) sub-scales. Clinical variables included: pain (NRPS-11), disability (RMQ), evolution, previous treatments and diagnostic imaging. The sociodemographic variables included: gender, age, educational level, and employment status. Just over half (51.7%) of the subjects had high FA on the FABQ-PA sub-scale. Sick leave (SL) [β=24.45 (P=.009 * ); β=13.03 (P=.016 * ); β=14.04 (P=.011 * ) for FABQ, FABQ-PA and FABQ-W, respectively]; primary studies level [β=15.09 (P=.01 * ); β=9.73 (P=.01 * ) for FABQ and FABQ-PA], and disability [β=1.45 (P<.001); β=0.61 (P<.001); β=0.68 (P<.001) for FABQ, FABQ-PA and FABQ-W, respectively] were associated with FA when they were modeled by multivariate regression. Some sociodemographic and clinical features of the NCLBP population are presented. Imaging tests (81.63%) and previous passive treatments (55.78%) could reflect problems of adherence to recommendations of CPGs. Sick leave, primary studies level, and disability were associated with FA. The findings should be interpreted in the light of possible limitations. Some suggestions for clinical practice are provided. Copyright © 2017 Elsevier España, S.L.U. All rights reserved.

The effect of 12-wk ω-3 fatty acid supplementation on in vivo thalamus glutathione concentration in patients "at risk" for major depression.

PubMed

Duffy, Shantel L; Lagopoulos, Jim; Cockayne, Nicole; Lewis, Simon J G; Hickie, Ian B; Hermens, Daniel F; Naismith, Sharon L

2015-10-01

As life expectancy increases, the need to prevent major health disorders is clear. Depressive symptoms are common in older adults and are associated with cognitive decline and greater risk for transitioning to major depression. Oxidative stress may be implicated in the pathophysiology of major depression and can be measured in vivo using proton magnetic resonance spectroscopy via the neurometabolite glutathione (GSH). Evidence suggests ω-3 fatty acid (FA) supplementation may prevent depression and directly affect GSH concentration. The aim of this study was to examine the effect of ω-3 FA supplementation on in vivo GSH concentration in older adults at risk for depression. Fifty-one older adults at risk for depression were randomized to receive either four 1000-mg ω-3 FA supplements daily (containing eicosapentaenoic acid 1200 mg plus docosahexaenoic acid 800 mg) or placebo (four 1000-mg paraffin oil placebo capsules daily) for 12 wk. Participants underwent magnetic resonance spectroscopy, as well as medical, neuropsychological, and self-report assessments at baseline and after 12 wk of supplementation. GSH was measured in the thalamus and calculated as a ratio to creatine. Depressive symptoms were measured using the Patient Health Questionnaire. Compared with the group given the ω-3 FA supplements, the placebo group had greater change in the GSH-to-creatine ratio in the thalamus (t = 2.00; P = 0.049) after the 12 wk intervention. This increase was in turn associated with a worsening of depressive symptoms (r = 0.43; P = 0.043). Depressive symptom severity in older adults appears to be associated with increased brain levels of GSH, a key marker of oxidative stress. Importantly, ω-3 FA supplementation may attenuate oxidative stress mechanisms, thereby offering benefits for depression prevention. Copyright © 2015 Elsevier Inc. All rights reserved.

GS-Nitroxide (JP4-039)-Mediated Radioprotection of Human Fanconi Anemia Cell Lines

PubMed Central

Bernard, Mark E.; Kim, Hyun; Berhane, Hebist; Epperly, Michael W.; Franicola, Darcy; Zhang, Xichen; Houghton, Frank; Shields, Donna; Wang, Hong; Bakkenist, Christopher J.; Frantz, Marie-Celine; Forbeck, Erin M.; Goff, Julie P.; Wipf, Peter; Greenberger, Joel S.

2011-01-01

Fanconi anemia (FA) is an inherited disorder characterized by defective DNA repair and cellular sensitivity to DNA crosslinking agents. Clinically, FA is associated with high risk for marrow failure, leukemia and head and neck squamous cell carcinoma (HNSCC). Radiosensitivity in FA patients compromises the use of total-body irradiation for hematopoietic stem cell transplantation and radiation therapy for HNSCC. A radioprotector for the surrounding tissue would therefore be very valuable during radiotherapy for HNSCC. Clonogenic radiation survival curves were determined for pre- or postirradiation treatment with the parent nitroxide Tempol or JP4-039 in cells of four FA patient-derived cell lines and two transgene-corrected subclonal lines. FancG–/– (PD326) and FancD2–/– (PD20F) patient lines were more sensitive to the DNA crosslinking agent mitomycin C (MMC) than their transgene-restored subclonal cell lines (both P < 0.0001). FancD2–/– cells were more radiosensitive than the transgene restored subclonal cell line (ñ = 2.0 ± 0.7 and 4.7 ± 2.2, respectively, P = 0.03). In contrast, FancG–/– cells were radioresistant relative to the transgene-restored subclonal cell line (ñ = 9.4 ± 1.5 and 2.2 ± 05, respectively, P = 0.001). DNA strand breaks measured by the comet assay correlated with radiosensitivity. Cell lines from a Fanc-C and Fanc-A patients showed radiosensitivity similar to that of Fanc-D2–/– cells. A fluorophore-tagged JP4-039 (BODIPY-FL) analog targeted the mitochondria of the cell lines. Preirradiation or postirradiation treatment with JP4-039 at a lower concentration than Tempol significantly increased the radioresistance and stabilized the antioxidant stores of all cell lines. Tempol increased the toxicity of MMC in FancD2–/– cells. These data provide support for the potential clinical use of JP4-039 for normal tissue radioprotection during chemoradiotherapy in FA patients. PMID:21939290

GS-nitroxide (JP4-039)-mediated radioprotection of human Fanconi anemia cell lines.

PubMed

Bernard, Mark E; Kim, Hyun; Berhane, Hebist; Epperly, Michael W; Franicola, Darcy; Zhang, Xichen; Houghton, Frank; Shields, Donna; Wang, Hong; Bakkenist, Christopher J; Frantz, Marie-Celine; Forbeck, Erin M; Goff, Julie P; Wipf, Peter; Greenberger, Joel S

2011-11-01

Fanconi anemia (FA) is an inherited disorder characterized by defective DNA repair and cellular sensitivity to DNA crosslinking agents. Clinically, FA is associated with high risk for marrow failure, leukemia and head and neck squamous cell carcinoma (HNSCC). Radiosensitivity in FA patients compromises the use of total-body irradiation for hematopoietic stem cell transplantation and radiation therapy for HNSCC. A radioprotector for the surrounding tissue would therefore be very valuable during radiotherapy for HNSCC. Clonogenic radiation survival curves were determined for pre- or postirradiation treatment with the parent nitroxide Tempol or JP4-039 in cells of four FA patient-derived cell lines and two transgene-corrected subclonal lines. FancG(-/-) (PD326) and FancD2(-/-) (PD20F) patient lines were more sensitive to the DNA crosslinking agent mitomycin C (MMC) than their transgene-restored subclonal cell lines (both P < 0.0001). FancD2(-/-) cells were more radiosensitive than the transgene restored subclonal cell line (ñ = 2.0 ± 0.7 and 4.7 ± 2.2, respectively, P = 0.03). In contrast, FancG(-/-) cells were radioresistant relative to the transgene-restored subclonal cell line (ñ = 9.4 ± 1.5 and 2.2 ± 05, respectively, P = 0.001). DNA strand breaks measured by the comet assay correlated with radiosensitivity. Cell lines from a Fanc-C and Fanc-A patients showed radiosensitivity similar to that of Fanc-D2(-/-) cells. A fluorophore-tagged JP4-039 (BODIPY-FL) analog targeted the mitochondria of the cell lines. Preirradiation or postirradiation treatment with JP4-039 at a lower concentration than Tempol significantly increased the radioresistance and stabilized the antioxidant stores of all cell lines. Tempol increased the toxicity of MMC in FancD2(-/-) cells. These data provide support for the potential clinical use of JP4-039 for normal tissue radioprotection during chemoradiotherapy in FA patients.

Strain Gage Loads Calibration Testing of the Active Aeroelastic Wing F/A-18 Aircraft

NASA Technical Reports Server (NTRS)

Lokos, William A.; Olney, Candida D.; Chen, Tony; Crawford, Natalie D.; Stauf, Rick; Reichenbach, Eric Y.; Bessette, Denis (Technical Monitor)

2002-01-01

This report describes strain-gage calibration loading through the application of known loads of the Active Aeroelastic Wing F/A-18 airplane. The primary goal of this test is to produce a database suitable for deriving load equations for left and right wing root and fold shear; bending moment; torque; and all eight wing control-surface hinge moments. A secondary goal is to produce a database of wing deflections measured by string potentiometers and the onboard flight deflection measurement system. Another goal is to produce strain-gage data through both the laboratory data acquisition system and the onboard aircraft data system as a check of the aircraft system. Thirty-two hydraulic jacks have applied loads through whiffletrees to 104 tension-compression load pads bonded to the lower wing surfaces. The load pads covered approximately 60 percent of the lower wing surface. A series of 72 load cases has been performed, including single-point, double-point, and distributed load cases. Applied loads have reached 70 percent of the flight limit load. Maximum wingtip deflection has reached nearly 16 in.

Determination of the stability and control derivatives of the NASA F/A-18 HARV using flight data

NASA Technical Reports Server (NTRS)

Napolitano, Marcello R.; Spagnuolo, Joelle M.

1993-01-01

This report documents the research conducted for the NASA-Ames Cooperative Agreement No. NCC 2-759 with West Virginia University. A complete set of the stability and control derivatives for varying angles of attack from 10 deg to 60 deg were estimated from flight data of the NASA F/A-18 HARV. The data were analyzed with the use of the pEst software which implements the output-error method of parameter estimation. Discussions of the aircraft equations of motion, parameter estimation process, design of flight test maneuvers, and formulation of the mathematical model are presented. The added effects of the thrust vectoring and single surface excitation systems are also addressed. The results of the longitudinal and lateral directional derivative estimates at varying angles of attack are presented and compared to results from previous analyses. The results indicate a significant improvement due to the independent control surface deflections induced by the single surface excitation system, and at the same time, a need for additional flight data especially at higher angles of attack.

Omega-3 fatty acid treatment of children with attention-deficit hyperactivity disorder: A randomized, double-blind, placebo-controlled study

PubMed Central

Bélanger, Stacey Ageranioti; Vanasse, Michel; Spahis, Schohraya; Sylvestre, Marie-Pierre; Lippé, Sarah; l’Heureux, François; Ghadirian, Parviz; Vanasse, Catherine-Marie; Levy, Emile

2009-01-01

BACKGROUND: Although several clinical trials have evaluated the impact of n-3 polyunsaturated fatty acid (PUFA) on patients with attention-deficit hyperactivity disorder (ADHD), changes in plasma PUFA composition were not always assessed following n-3 supplementation. Furthermore, no reports are available on the efficacy of n-3 PUFA in Canadian youth with ADHD. OBJECTIVES: To determine fatty acid (FA) composition, and the efficacy and safety of n-3 PUFA supplementation on ADHD clinical symptoms in French Canadian primary school children. PATIENTS AND METHODS: The Strengths and Weaknesses in ADHD and Normal Behaviors (SWAN) and Conners’ questionnaires were used to assess changes in ADHD symptoms in 37 children (only 26 children completed the study from zero to 16 weeks). They were divided into two groups (A and B), and participated in a 16-week, double-blind, one-way, crossover randomized study. In the first phase, group A received the n-3 PUFA supplement and group B received n-6 PUFA (sunflower oil) as a placebo. During the second phase, group B received the active n-3 PUFA supplement that was continued in group A. FA composition and lipid profile were assessed during the phases of the study. RESULTS: FA differences between groups were observed in the 26 patients. Supplementation with n-3 PUFA resulted in significant increases in eicosapentaenoic and docosahexaenoic acids in group A, while group B was enriched with alpha-linolenic, gamma-linolenic and homo-gamma-linolenic acids. The n-3 PUFA supplement was tolerated without any adverse effects. A statistically significant improvement in symptoms was noted based on the parent version of the Conners’ questionnaire from baseline to the end of phase 1, and this amelioration continued from phases 1 to 2, although the latter changes from phases 1 and 2 were not statistically significant in any of the subscales except for the subscale measuring inattention in group B. The improvement was greater in patients from group A in phase 1 and in patients from group B in phase 2. A subgroup of eight patients (four in each group) displayed a statistically significant clinical improvement following the administration of the n-3 PUFA supplement, particularly for the inattention and global Diagnostic and Statistical Manual of Mental Disorders, Fourth edition, total Conners’ subscales. CONCLUSIONS: A subgroup of children with ADHD who used n-3 PUFA supplements achieved and maintained symptom control. The data of the present study also supported n-3 PUFA safety and tolerability, but limited changes were noted in the FA profile in French Canadians with ADHD. PMID:19436468

White matter abnormalities and their impact on attentional performance in adult attention-deficit/hyperactivity disorder.

PubMed

Konrad, Andreas; Dielentheis, Thomas F; El Masri, Dschamil; Dellani, Paulo R; Stoeter, Peter; Vucurevic, Goran; Winterer, Georg

2012-06-01

Inattention is the most important behavioral feature of adult patients with attention-deficit/hyperactivity disorder (ADHD). Neuroimaging studies in ADHD have demonstrated abnormalities primarily in the frontostriatal circuitry and were mostly conducted in children. We investigated white matter (WM) integrity in adult ADHD patients and the correlation of WM microstructure and neuropsychological parameters in 37 (21 men) never-medicated adult ADHD patients and 34 age- and gender-matched healthy controls. All subjects underwent clinical interviews, rating scales, and neuropsychological tests of attentional performance. Diffusion tensor imaging (DTI) was acquired, and 12 WM regions-of-interest (ROIs) within the attentional network were chosen. Group differences of mean fractional anisotropy (FA) and mean diffusivity (MD) values were calculated for each ROI, and patients' DTI measures were then correlated with measures of attentional performance. FA values in ADHD patients were significantly reduced in the left inferior longitudinal fasciculus (ILF), while MD values were significantly increased in ADHD patients in the frontal portion of the left frontooccipital fasciculus (IFO). In ADHD patients, MD values were negatively correlated with attentional performance in the left ILF. Our findings provide further support for disturbed frontostriatal structural connectivity and also point to an involvement of the left temporal white matter with an impact on attentional performance.

Diffuse emission and control of copper in urban surface runoff.

PubMed

Boller, M A; Steiner, M

2002-01-01

Copper washed off from roofs and roads is considered to be a major contribution to diffuse copper pollution of urban environments. In order to guarantee sustainable protection of soils and water, the long-term strategy is to avoid or replace copper containing materials on roofs and fagades. Until achievement of this goal, a special adsorber system is suggested to control the diffuse copper fluxes by retention of copper by a mixture of granulated iron-hydroxide (GEH) and calcium carbonate. Since future stormwater runoff concepts are based on decentralised runoff infiltration into the underground, solutions are proposed which provide for copper retention in infiltration sites using GEH adsorption layers. The example of a large copper façade of which the runoff is treated in an adsorption trench reveals the first full-scale data on façade runoff and adsorber performance. During the first year of investigation average façade runoff concentrations in the range of 1-10 mg Cu/l are reduced by 96-99% in the adsorption ditch.

Metal-organic gel enhanced fluorescence anisotropy for sensitive detection of prostate specific antigen

NASA Astrophysics Data System (ADS)

Zhao, Ting Ting; Peng, Zhe Wei; Yuan, Dan; Zhen, Shu Jun; Huang, Cheng Zhi; Li, Yuan Fang

2018-03-01

In this contribution, we demonstrated that Cu-based metal-organic gel (Cu-MOG) was able to serve as a novel amplification platform for fluorescence anisotropy (FA) assay for the first time, which was confirmed by the sensitive detection of a common cancer biomarker, prostate specific antigen (PSA). The dye-labeled probe aptamer (PA) product was adsorbed onto the benzimidazole derivative-containing Cu-MOG via electrostatic incorporation and strong π-π stacking interactions, which significantly increased the FA value due to the enlargement of the molecular volume of the PA/Cu-MOG complex. With the introduction of target PSA, the FA value was obviously decreased on account of the specific recognition between PSA and PA which resulted in the detachment of PA from the surface of MOG. The linear range was from 0.5-8 ng/mL, with a detection limit of 0.33 ng/mL. Our work has thus helped to demonstrate promising application of MOG material in the fields of biomolecules analysis and disease diagnosis.

Mandibular arch form: the relationship between dental and basal anatomy.

PubMed

Ronay, Valerie; Miner, R Matthew; Will, Leslie A; Arai, Kazuhito

2008-09-01

We investigated mandibular dental arch form at the levels of both the clinically relevant application points of the orthodontic bracket and the underlying anatomic structure of the apical base. The correlation of both forms was evaluated and examined to determine whether the basal arch could be used to derive a standardized clinical arch form. Thirty-five mandibular dental casts (skeletal and dental Class I) were laser scanned, and a 3-dimensional virtual model was created. Two reference points (FA, the most prominent part of the central lobe on each crown's facial surface, and WALA, a point at the height of the mucogingival junction) were selected for each tooth from the right to the left first molars. The FA and WALA arch forms were compared, and the distances between corresponding points and intercanine and intermolar widths were analyzed. Both arch forms were highly individual and the tooth values scattered. Nevertheless, a highly significant relationship between the FA and WALA curves was found, especially in the canine (0.75) and molar (0.87) areas. Both FA and WALA point-derived arch forms were individual and therefore could not be defined by a generalized shape. WALA points proved to be a useful representation of the apical base and helpful in the predetermination of an individualized dental arch form.

Novel biocomposite of carboxymethyl chitosan and pineapple peel carboxymethylcellulose as sunscreen carrier.

PubMed

Wongkom, Lucksanee; Jimtaisong, Ampa

2017-02-01

This study aims to prepare of biocomposite of carboxymethyl chitosan (CM-chitosan) and carboxymethylcellulose (CMC) from Ananas comosus (pineapple) peel for use as broad spectrum sunscreen carrier. Biocomposite was produced by using ferulic acid (FA), a plant extract, as crosslinker with the optimal ratio of CMC: CM-chitosan: FA at 1:2:4%w. FT-IR technique demonstrated that crosslinking may occur at amine group of CM-chitosan and carboxyl group of FA and hydrogen bonding between hydroxyl group of CMC and carboxyl group of FA. Biocomposite is pale yellow powder and present fibre bundle-like surface in the SEM image. DSC, TGA and XRD results indicated that new compound was formed. The particle size of biocomposite is 626nm determined by using Zetasizer. Hydrophilic TiO 2 and phenylbenzimidazole sulphonic acid (PBSA) were used as sunscreen agent at ratio of TiO 2 : PBSA at 2:1%w. The biocomposite sunscreen possesses the SPF value of 2.47 with boost star rating of 3 at 2% compound. The results obtained indicate that the biocomposite was successfully prepared from CM-chitosan and pineapple peel CMC and the system can be used as matrix delivery system for hydrophilic sunscreens. Copyright © 2016 Elsevier B.V. All rights reserved.

Diabetes-associated microbiota in fa/fa rats is modified by Roux-en-Y gastric bypass.

PubMed

Arora, Tulika; Seyfried, Florian; Docherty, Neil G; Tremaroli, Valentina; le Roux, Carel W; Perkins, Rosie; Bäckhed, Fredrik

2017-09-01

Roux-en-Y gastric bypass (RYGB) and duodenal jejunal bypass (DJB), two different forms of bariatric surgery, are associated with improved glucose tolerance, but it is not clear whether the gut microbiota contributes to this effect. Here we used fa/fa rats as a model of impaired glucose tolerance to investigate whether (i) the microbiota varies between fa/fa and nondiabetic fa/+ rats; (ii) the microbiota of fa/fa rats is affected by RYGB and/or DJB; and (iii) surgically induced microbiota alterations contribute to glucose metabolism. We observed a profound expansion of Firmicutes (specifically, Lactobacillus animalis and Lactobacillus reuteri) in the small intestine of diabetic fa/fa compared with nondiabetic fa/+ rats. RYGB-, but not DJB-, treated fa/fa rats exhibited greater microbiota diversity in the ileum and lower L. animalis and L. reuteri abundance compared with sham-operated fa/fa rats in all intestinal segments, and their microbiota composition resembled that of unoperated fa/+ rats. To investigate the functional role of RYGB-associated microbiota alterations, we transferred microbiota from sham- and RYGB-treated fa/fa rats to germ-free mice. The metabolic phenotype of RYGB-treated rats was not transferred by the transplant of ileal microbiota. In contrast, postprandial peak glucose levels were lower in mice that received cecal microbiota from RYGB- versus sham-operated rats. Thus, diabetes-associated microbiota alterations in fa/fa rats can be modified by RYGB, and modifications in the cecal microbiota may partially contribute to improved glucose tolerance after RYGB.

Involvement of the right hemisphere in reading comprehension: a DTI study

PubMed Central

Horowitz-Kraus, Tzipi; Wang, Yingying; Plante, Elena; Holland, Scott K.

2014-01-01

The Simple View of reading emphasizes the critical role of two factors in normal reading skills: word recognition and reading comprehension. The current study aims to identify the anatomical support for aspects of reading performance that fall within these two components. Fractional anisotropy (FA) values were obtained from Diffusion Tensor images in twenty-one typical adolescents and young adults using the Tract Based Spatial Statistics (TBSS) method. We focused on the Arcuate Fasciculus (AF) and Inferior Longitudinal Fasciculus (ILF) as fiber tracts that connect regions already implicated in the distributed cortical network for reading. Our results demonstrate dissociation between word-level and narrative-level reading skills: the FA values for both left and right ILF were correlated with measures of word reading, while only the left ILF correlated with reading comprehension scores. FA in the AF, however, correlated only with reading comprehension scores, bilaterally. Correlations with the right AF were particularly robust, emphasizing the contribution of the right hemisphere, especially the frontal lobe, to reading comprehension performance on the particular passage comprehension test used in this study. The anatomical dissociation between these reading skills is supported by the Simple View theory and may shed light on why these two skills dissociate in those with reading disorders. PMID:24909792

The mechanisms underlying overgeneral autobiographical memory: An evaluative review of evidence for the CaR-FA-X model

PubMed Central

Sumner, Jennifer A.

2011-01-01

Overgeneral autobiographical memory (OGM) has been found to be an important cognitive phenomenon with respect to depression and trauma-related psychopathology (e.g., posttraumatic stress disorder), and researchers have been interested in better understanding the factors that contribute to this proposed vulnerability factor. The most prominent model of mechanisms underlying OGM to date is Williams et al.’s (2007) CaR-FA-X model. This model proposes that three processes influence OGM: capture and rumination, functional avoidance, and impaired executive control. The author reviews the current state of support for the CaR-FA-X model by evaluating 38 studies that have examined OGM and one or more mechanisms of the model. Collectively, these studies reveal robust support for associations between OGM and both rumination and impaired executive control. OGM also appears to be a cognitive avoidance strategy, and there is evidence that avoiding the retrieval of specific memories reduces distress after an aversive event, at least in the short term. Important issues that have been left unresolved are highlighted, including the nature of the capture phenomenon, the role of trauma in functional avoidance, and the developmental nature of functional avoidance. Recommendations for future research that will enhance understanding of the factors that contribute to OGM are suggested. PMID:22142837

Mouth self-examination as a screening tool for oral cancer in a high-risk group of patients with Fanconi anemia.

PubMed

Furquim, Camila Pinheiro; Pivovar, Allana; Cavalcanti, Laura Grein; Araújo, Renata Fuentes; Sales Bonfim, Carmem Maria; Torres-Pereira, Cassius Carvalho

2014-10-01

Oral cancer usually occurs at accessible sites, enabling early detection by visual inspection. Fanconi anemia (FA) is a recessive disorder associated with a high risk of developing head and neck solid tumors. The aim of this study was to assess the ability to perform mouth self-examination (MSE) in these patients. A total of 44 patients with FA, aged ≥ 18 years, were given a self-reported questionnaire to collect sociodemographic data and information about health-related behaviors and oral cancer awareness. They were asked to perform MSE, which was evaluated using criteria for mucosal visualization and retracting ability. Subsequently, an oral medicine specialist clinically examined all participants, and these findings were considered to be the gold standard. The sensitivity and specificity values of MSE were 43% and 44%, respectively. The MSE accuracy was 43%. Most patients (73%) reported that MSE was easy or very easy, although 75% showed insufficient performance. The accuracy of MSE alone is not sufficient to indicate whether MSE should be recommended as a strategy to prevent oral cancer in patients with FA. Nevertheless, the present results indicate that this inexpensive technique could be used as a tool for early detection of cancer in these patients. Copyright © 2014 Elsevier Inc. All rights reserved.

Mass Measurements of Focal Adhesions in Single Cells Using High Resolution Surface Plasmon Resonance Microscopy.

PubMed

Peterson, Alexander W; Halter, Michael; Tona, Alessandro; Plant, Anne L; Elliott, John T

2018-01-01

Surface plasmon resonance microscopy (SPRM) is a powerful label-free imaging technique with spatial resolution approaching the optical diffraction limit. The high sensitivity of SPRM to small changes in index of refraction at an interface allows imaging of dynamic protein structures within a cell. Visualization of subcellular features, such as focal adhesions (FAs), can be performed on live cells using a high numerical aperture objective lens with a digital light projector to precisely position the incident angle of the excitation light. Within the cell-substrate region of the SPRM image, punctate regions of high contrast are putatively identified as the cellular FAs. Optical parameter analysis is achieved by application of the Fresnel model to the SPRM data and resulting refractive index measurements are used to calculate protein density and mass. FAs are known to be regions of high protein density that reside at the cell-substratum interface. Comparing SPRM with fluorescence images of antibody stained for vinculin, a component in FAs, reveals similar measurements of FA size. In addition, a positive correlation between FA size and protein density is revealed by SPRM. Comparing SPRM images for two cell types reveals a distinct difference in the protein density and mass of their respective FAs. Application of SPRM to quantify mass can greatly aid monitoring basic processes that control FA mass and growth and contribute to accurate models that describe cell-extracellular interactions.

Is the onset of obesity in suckling fa/fa rats linked to a potentially larger milk intake?

PubMed

Buchberger, P; Schmidt, I

1996-08-01

We wanted to find out whether fatty (fa/fa) sucklings show abnormal intake when given access to an abundant milk reservoir. To do this, we gravimetrically determined the milk ingested by small groups (4-5 pups) of 5- to 15-day-old lean (+/fa) and fatty littermates allowed to suckle for 30 min after their mother had not been nursing for periods of between 1 and 7 h. The pups were grouped randomly and their phenotypes retrospectively identified. Within both genotypes, the intakes of simultaneously tested pups were significantly higher in pups deprived for longer periods. Deprived and undeprived fa/fa pups ingested, however, slightly but significantly less milk than +/fa littermates did in the same nursing bout. In the first 2 wk of life, when fa/fa pups deposit nearly twice as much body fat as their +/fa littermates do, fa/fa pups will thus suckle less rather than more milk. This extends previous findings showing that the onset of fa/fa obesity is independent of larger intakes and thus questions that fa impairs a receptor primarily controlling food intake.

Diabetes-associated microbiota in fa/fa rats is modified by Roux-en-Y gastric bypass

PubMed Central

Arora, Tulika; Seyfried, Florian; Docherty, Neil G; Tremaroli, Valentina; le Roux, Carel W; Perkins, Rosie; Bäckhed, Fredrik

2017-01-01

Roux-en-Y gastric bypass (RYGB) and duodenal jejunal bypass (DJB), two different forms of bariatric surgery, are associated with improved glucose tolerance, but it is not clear whether the gut microbiota contributes to this effect. Here we used fa/fa rats as a model of impaired glucose tolerance to investigate whether (i) the microbiota varies between fa/fa and nondiabetic fa/+ rats; (ii) the microbiota of fa/fa rats is affected by RYGB and/or DJB; and (iii) surgically induced microbiota alterations contribute to glucose metabolism. We observed a profound expansion of Firmicutes (specifically, Lactobacillus animalis and Lactobacillus reuteri) in the small intestine of diabetic fa/fa compared with nondiabetic fa/+ rats. RYGB-, but not DJB-, treated fa/fa rats exhibited greater microbiota diversity in the ileum and lower L. animalis and L. reuteri abundance compared with sham-operated fa/fa rats in all intestinal segments, and their microbiota composition resembled that of unoperated fa/+ rats. To investigate the functional role of RYGB-associated microbiota alterations, we transferred microbiota from sham- and RYGB-treated fa/fa rats to germ-free mice. The metabolic phenotype of RYGB-treated rats was not transferred by the transplant of ileal microbiota. In contrast, postprandial peak glucose levels were lower in mice that received cecal microbiota from RYGB- versus sham-operated rats. Thus, diabetes-associated microbiota alterations in fa/fa rats can be modified by RYGB, and modifications in the cecal microbiota may partially contribute to improved glucose tolerance after RYGB. PMID:28524868

Algae façade as green building method: application of algae as a method to meet the green building regulation

NASA Astrophysics Data System (ADS)

Poerbo, Heru W.; Martokusumo, Widjaja; Donny Koerniawan, M.; Aulia Ardiani, Nissa; Krisanti, Susan

2017-12-01

The Local Government of Bandung city has stipulated a Green Building regulation through the Peraturan Walikota Number 1023/2016. Signed by the mayor in October 2016, Bandung became the first city in Indonesia that put green building as mandatory requirement in the building permit (IMB) process. Green Building regulation is intended to have more efficient consumption of energy and water, improved indoor air quality, management of liquid and solid waste etc. This objective is attained through various design method in building envelope, ventilation and air conditioning system, lighting, indoor transportation system, and electrical system. To minimize energy consumption of buildings that have large openings, sun shading device is often utilized together with low-E glass panes. For buildings in hot humid tropical climate, this method reduces indoor air temperature and thus requires less energy for air conditioning. Indoor air quality is often done by monitoring the carbon dioxide levels. Application of algae as part of building system façade has recently been introduced as replacement of large glass surface in the building façade. Algae are not yet included in the green building regulation because it is relatively new. The research will investigate, with the help of the modelling process and extensive literature, how effective is the implementation of algae in building façade to reduce energy consumption and improve its indoor air quality. This paper is written based on the design of ITB Innovation Park as an ongoing architectural design-based research how the algae-integrated building façade affects the energy consumption.

Zein nanoparticles as delivery systems for covalently linked and physically entrapped folic acid

NASA Astrophysics Data System (ADS)

Chuacharoen, Thanida; Sabliov, Cristina M.

2017-02-01

Zein nanoparticles covalently linked to folic acid were hypothesized to sustain the release of the folic acid in addition to targeting cancer cells overexpressing folate-binding receptors, whereas zein nanoparticles with physically entrapped folic acid would only be able to control the release of the bioactive without targeting of cancer cells. The two types of particles, folic acid covalently linked zein nanoparticles (ZN-FA nps) and zein nanoparticles with entrapped folic acid (ZN(FA) nps), were synthesized and the covalent link between folic acid and zein was assessed by Fourier transform infrared spectroscopy (FTIR) and nuclear magnetic resonance spectroscopy (1H NMR). Their size, polydispersity index, zeta potential, morphology, and loading capacity were evaluated by dynamic light scattering (DLS), transmission electron microscopy (TEM), and spectrophotometric technique. The release studies of the folic acid preformed in phosphate-buffered saline (PBS) at 37 °C for 7 days concluded that the release of the loaded folic acid was sustained over 7 days for both systems. The cytotoxicity was investigated using a methyl thiazolyl tetrazolium (MTT) assay, and the results showed that zein nanoparticles were biocompatible to HeLa (an overexpressing folate receptor cells) and A549 (a deficient folate receptor cells) cells, which have different levels of folate receptors on surface and both folic acid nanoparticle systems were able to diminish the adverse toxic effect of folic acid to cells. The increased uptake of ZN-FA nps relative to ZN(FA) nps supported the use of ZN-FA nps as targeting nanoagents to cells overexpressing folate receptors.

Three-Dimensional Imaging of Lipids and Metabolites in Tissues by Nanospray Desorption Electrospray Ionization Mass Spectrometry

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

Lanekoff, Ingela T.; Burnum-Johnson, Kristin E.; Thomas, Mathew

Abstract Three-dimensional (3D) imaging of tissue sections is a new frontier in mass spectrometry imaging (MSI). Here we report on fast 3D imaging of lipids and metabolites associated with mouse uterine decidual cells and embryo at the implantation site on day 6 of pregnancy. 2D imaging of 16-20 serial tissue sections deposited on the same glass slide was performed using nanospray desorption electrospray ionization (nano-DESI) – an ambient ionization technique that enables sensitive localized analysis of analytes on surfaces without special sample pre-treatment. In this proof-of-principle study, nano-DESI was coupled to a high-resolution Q-Exactive instrument operated at high repetition ratemore » of >5 Hz with moderate mass resolution of 35,000 (m/Δm at m/z 200), which enabled acquisition of the entire 3D image with a spatial resolution of ~150 μm in less than 4.5 hours. The results demonstrate localization of acetylcholine in the primary decidual zone (PDZ) of the implantation site throughout the depth of the tissue examined, indicating an important role of this signaling molecule in decidualization. Choline and phosphocholine – metabolites associated with cell growth – are enhanced in the PDZ and abundant in other cellular regions of the implantation site. Very different 3D distributions were obtained for fatty acids (FA), oleic acid and linoleic acid (FA 18:1 and FA 18:2), differing only by one double bond. Localization of FA 18:2 in the PDZ indicates its important role in decidualization while FA 18:1 is distributed more evenly throughout the tissue. In contrast, several lysophosphatidylcholines (LPC) observed in this study show donut-like distributions with localization around the PDZ. Complementary distributions with minimal overlap were observed for LPC 18:0 and FA 18:2 while the 3D image of the potential precursor phosphatidylcholine (PC 36:2) showed a significant overlap with both LPC 18:0 and FA 18:2.« less

Feeding ecology of mesopelagic zooplankton of the subtropical and subarctic North Pacific Ocean determined with fatty acid biomarkers

NASA Astrophysics Data System (ADS)

Wilson, S. E.; Steinberg, D. K.; Chu, F.-L. E.; Bishop, J. K. B.

2010-10-01

Mesopelagic zooplankton may meet their nutritional and metabolic requirements in a number of ways including consumption of sinking particles, carnivory, and vertical migration. How these feeding modes change with depth or location, however, is poorly known. We analyzed fatty acid (FA) profiles to characterize zooplankton diet and large particle (>51 μm) composition in the mesopelagic zone (base of euphotic zone -1000 m) at two contrasting time-series sites in the subarctic (station K2) and subtropical (station ALOHA) Pacific Ocean. Total FA concentration was 15.5 times higher in zooplankton tissue at K2, largely due to FA storage by seasonal vertical migrators such as Neocalanus and Eucalanus. FA biomarkers specific to herbivory implied a higher plant-derived food source at mesotrophic K2 than at oligotrophic ALOHA. Zooplankton FA biomarkers specific to dinoflagellates and diatoms indicated that diatoms, and to a lesser extent, dinoflagellates were important food sources at K2. At ALOHA, dinoflagellate FAs were more prominent. Bacteria-specific FA biomarkers in zooplankton tissue were used as an indicator of particle feeding, and peaks were recorded at depths where known particle feeders were present at ALOHA (e.g., ostracods at 100-300 m). In contrast, depth profiles of bacterial FA were relatively constant with depth at K2. Diatom, dinoflagellate, and bacterial biomarkers were found in similar proportions in both zooplankton and particles with depth at both locations, providing additional evidence that mesopelagic zooplankton consume sinking particles. Carnivory indices were higher and increased significantly with depth at ALOHA, and exhibited distinct peaks at K2, representing an increase in dependence on other zooplankton for food in deep waters. Our results indicate that feeding ecology changes with depth as well as by location. These changes in zooplankton feeding ecology from the surface through the mesopelagic zone, and between contrasting environments, have important consequences for the quality and quantity of organic material available to deeper pelagic and benthic food webs, and for organic matter sequestration.

Chemical properties of peat used in balneology

NASA Astrophysics Data System (ADS)

Szajdak, L.; Hładoń, T.

2009-04-01

The physiological activity of peats is observed in human peat-bath therapy and in the promotion of growth in some plants. Balneological peat as an ecologically clean and natural substance is perceived as being more 'human friendly' than synthetic compounds. Poland has a long tradition of using balneological peat for therapeutic purposes. Balneological peat reveals a physical effect by altering temperature and biochemical effects through biologically active substances. It is mainly used for the treatment of rheumatic diseases that are quite common in Poland. Peat represents natural product. Physico-chemical properties of peat in particular surface-active, sorption and ion exchanges, defining their biological function, depend mainly on the chemical composition and molecular structure of humic substances representing the major constituent of organic soil (peat). The carbon of organic matter of peats is composed of 10 to 20% carbohydrates, primarily of microbial origin; 20% nitrogen-containing constituents, such as amino acids and amino sugars; 10 to 20% aliphatic fatty acids, alkanes, etc.; with the rest of carbon being aromatic. For balneology peat should be highly decomposed (preferably H8), natural and clean. The content of humic acids should exceed 20% of dry weight, ash content will be less than 15 15% of dry weight, sulphur content less than 0.3% of dry weight and the amount of water more than 85%. It will not contain harmful bacteria and heavy metals. Humic substances (HS) of peat are known to be macromolecular polydisperse biphyllic systems including both hydrophobic domains (saturated hydrocarbon chains, aromatic structural units) and hydrophilic functional groups, i. e having amphiphilic character. Amphiphilic properties of FA are responsible for their solubility, viscosity, conformation, surfactant-like character and a variety of physicochemical properties of considerable biologically practical significance. The chemical composition of peats depends significantly on the genesis of peatlands and the depth of sampling. The chemical properties of peat fulvic acids (FA) have some genetic peculiarities due to the specific conditions of the process of humification of peat-forming plants in mires. The process of humification in mires takes place in the top-forming layer under amphibious moisture conditions. Substances of microbial origin are water-soluble and can participate in the formation of peat FA to a little extent. So a main source of structural units for the peat HA and FA is suggested to be organic constituents of peat forming plants of various botanical composition. The content of aromatic units in peat FA was shown to depend on the content of lignin in peat-forming plants and also of the aromatization of polysaccharides mainly due to the transformation of cellulose. FA characterized lower than humic acids molecular weight (1000-30,000). FA's are composed of a series of highly oxidized aromatic rings with a large number of side chains. Building blocks are benzene carboxylic acids and phenolic acids. These are held together by hydrogen bonding van der Waals' forces and ionic bonding. FA contains larger concentrations of nitrogen. This fraction also contains a great deal of polysaccharide materials, as well as low molecular fatty acids and cytoplasmic constituents of microorganisms. These compounds are linear, flexible colloids at low concentrations, and spherical colloids at high solution concentrations and low pH values. A more adequate knowledge of the chemical structure of humic materials will assist us in better understanding the physiological effects and also the function of these macromolecules on the health that these materials are know to exert. This improved knowledge provides us better information on chemical structure of humic substances from peats, which are responsible for pharmacotherapeutic, pharmacokinetic and biopharmaceutical effect. This structure of FA creates proper conditions for uptake of nutrient as well as bioavailability of biologically active substances. The solubilization in water by humic materials of organic substances which are otherwise water-insoluble is a matter of considerable interest to chemist deals with the problem of the function of organic matter. There has been considerable evidence that humic substances can "complex" with several biologically active substances and so modify their physiological activity. It has been noteworthy that FA can "fix" high-molecular weight water-insoluble organic compounds and make them water-soluble. FA may so act as a vehicle for the mobilization, transport and immobilization of such substances in physiological conditions. Analysis of HA and FA carried out by several analytical methods revealed that there were no chemical interaction among biologically active substances but that latter was firmly adsorbed, possible by hydrogen-bonding, on the FA surfaces. Amino acids account for the majority of organic N fraction in humic substances. Most of the amino acids in organic matter occur in bound form in the humino-peptides fraction. These amino acids are commonly bound to the central core of FA. These humino-peptides fraction of FA mediate in respiration and act as hydrogen acceptors, thus affecting oxidation-reaction reactions. Thus, what is needed at this time is more fundamental research in order to solve practical pharmacological, pharmacokinetic and biopharmaceutical problem of great significance for human health.

Health-related quality of life in children and adolescents who have a diagnosis of attention-deficit/hyperactivity disorder.

PubMed

Klassen, Anne F; Miller, Anton; Fine, Stuart

2004-11-01

The aim of treatment for attention-deficit/hyperactivity disorder (ADHD) is to decrease symptoms, enhance functionality, and improve well-being for the child and his or her close contacts. However, the measurement of treatment response is often limited to measuring symptoms using behavior rating scales and checklists completed by teachers and parents. Because so much of the focus has been on symptom reduction, less is known about other possible health problems, which can be measured easily using health-related quality-of-life (HRQL) questionnaires, which are designed to gather information across a range of health domains. The aim of our study was to measure HRQL in a clinic-based sample of children who had a diagnosis of ADHD and consider the impact of 2 clinical factors, symptom severity and comorbidity, on HRQL. Our specific hypotheses were that parent-reported HRQL would be poorer in children with ADHD than in normative US and Australian pediatric samples, in children with increasing severity of ADHD symptoms, and in children who had diagnoses of comorbid psychiatric disorders. Cross-sectional survey was conducted in British Columbia, Canada. The sample included 165 respondents of 259 eligible children (63.7% response rate) who were referred to the ADHD Clinic in British Columbia between November 2001 and October 2002. Children who are seen in this clinic come from all parts of the province and are diverse in terms of socioeconomic status and case mix. ADHD was diagnosed in 131 children, 68.7% of whom had a comorbid psychiatric disorder. Some children had >1 comorbidity: 23 had 2, 5 had 3, and 1 had 4. Fifty-one children had a comorbid learning disorder (LD), 45 had oppositional defiant disorder or conduct disorder (ODD/CD), and 27 had some other comorbid diagnosis. The mean age of children was 10 years (standard deviation: 2.8). Boys composed 80.9% (N = 106) of the sample. We used the 50-item parent version of the Child Health Questionnaire to measure physical and psychosocial health. Physical domains include the following: physical functioning (PF), role/social limitations as a result of physical health (RP), bodily pain/discomfort (BP), and general health perception (GH). Psychosocial domains include the following: role/social limitations as a result of emotional-behavioral problems (REB), self-esteem (SE), mental health (MH), general behavior (BE), emotional impact on parent (PTE), and time impact on parents (PTT). A separate domain measures limitations in family activities (FA). There is also a single-item measure of family cohesion (FC). Individual scale scores and summary scores for physical (PhS) and psychosocial health (PsS) can be computed. Symptom severity data (parent and teacher) came from the Child/Adolescent Symptom Inventory 4. These checklists provide information on symptoms for the 3 ADHD subtypes (inattentive, hyperactive, and combined). Each child underwent a comprehensive psychiatric assessment by 1 of 4 child psychiatrists. Documentation included a full 5-axis Diagnostic and Statistical Manual of Mental Disorders, Fourth Edition diagnosis on the basis of a comprehensive assessment. Clinical information for each child was extracted from hospital notes. Compared with both population samples, children with ADHD had comparable physical health but clinically important deficits in HRQL in all psychosocial domains, FA, FC, and PsS, with effect sizes as follows: FC = -0.66, SE = -0.90, MH = -0.97, PTT = -1.07, REB = -1.60, BE = -1.73, PTE = -1.87, FA = -1.95, and PsS = -1.98. Poorer HRQL for all domains of psychosocial health, FA, and PsS correlated significantly with more parent-reported inattentive, hyperactive, and combined symptoms of ADHD. Children with > or =2 comorbid disorders differed significantly from those with no comorbidity in most areas, including RP, GH, REB, BE, MH, SE, PTT, FA, and PsS, and from those with 1 comorbid disorder in 3 domains, including BE, MH, and FA and the PsS. The mean PsS score for children in the ODD/CD group (mean difference: -12.9; effect size = -1.11) and children in the other comorbidity group (-9.0; effect size = -.77) but not children in the LD group were significantly lower than children with no comorbid disorder. Predictors of physical health in a multiple regression model included child's gender (beta = .177) and number of comorbid conditions (beta = -.197). These 2 variables explained very little variation in the PhS. Predictors of psychosocial health included the number of comorbid conditions (beta = -.374) and parent-rated combined ADHD symptoms (beta = -.362). These 2 variables explained 31% of the variation in the PsS. Our study shows that ADHD has a significant impact on multiple domains of HRQL in children and adolescents. In support of our hypotheses, compared with normative data, children with ADHD had more parent-reported problems in terms of emotional-behavioral role function, behavior, mental health, and self-esteem. In addition, the problems of children with ADHD had a significant impact on the parents' emotional health and parents' time to meet their own needs, and they interfered with family activities and family cohesion. The differences that we found represent clinically important differences in HRQL. Our study adds new information about the HRQL of children with ADHD in relation to symptom severity and comorbidity. Children with more symptoms of ADHD had worse psychosocial HRQL. Children with multiple comorbid disorders had poorer psychosocial HRQL across a range of domains compared with children with none and 1 comorbid disorder. In addition, compared with children with no comorbidity, psychosocial HRQL was significantly lower in children with ODD/CD and children in the other comorbidity group but not in children with an LD. The demonstration of a differential impact of ADHD on health and well-being in relation to symptom severity and comorbidity has important implications for policies around eligibility for special educational and other supportive services. Because the impact of ADHD is not uniform, decisions about needed supports should incorporate a broader range of relevant indicators of outcome, including HRQL. Although many studies focus on measuring symptoms using rating scales and checklists, in our study, using a multidimensional questionnaire, we were able to show that many areas of health are affected in children with ADHD. We therefore argue that research studies of children with ADHD should include measurement of these broader domains of family impact and child health.

Digestion of fatty acids in ruminants: a meta-analysis of flows and variation factors. 1. Total fatty acids.

PubMed

Schmidely, P; Glasser, F; Doreau, M; Sauvant, D

2008-05-01

A database built from 95 experiments with 303 treatments was used to quantify the ruminal biohydrogenation (BH) of fatty acids (FA), efficiency of microbial protein synthesis (EMPS), duodenal flow and intestinal absorption of total FA and of FA with 12 to 18 C units, in response to variations in dietary FA content, source or technological treatment of fat supplement. Flows of FA were expressed relative to dry matter intake (DMI) to compile data from bovine and ovine species. BH tended to increase curvilinearly with FA intake, whereas dietary FA did not affect EMPS. A linear relationship between FA intake and duodenal flow of total FA was obtained, with a coefficient of 0.75 ± 0.06 g duodenal FA/kg DMI for each g FA intake/kg DMI. Between experiments, positive balances of total FA (intake - duodenum) were related to low EMPS. Relationships between duodenal flows of FA with 12 to 18 C units and their respective intakes were linear, with a coefficient that increased with the number of C units. Duodenal flow of bacterial FA was linearly related to FA intake (coefficient 0.33 ± 0.13), whereas contribution of bacterial lipid to duodenal flow decreased as FA intake increased. For each FA with 12 to 16 C units, prediction of FA absorption from its respective duodenal flow was linear. For total FA and FA with 18 C units, apparent absorption levelled off at high duodenal flows. All these relationships were discussed according to current knowledge on microbial metabolism in the rumen and on the intestinal digestibility of FA in the intestine.

The monuments of the UNESCO List under threat in the 21rst century: the Project "MONUNESCO-PARIS" (2012-2013)

NASA Astrophysics Data System (ADS)

Menendez, B.; Brimblecombe, P.; Deque, M.; Grossi, C. M.; Ionescu, A.; Lefevre, R. A.

2012-04-01

The banks of the River Seine in Paris are inscribed on the UNESCO List of the World Cultural Heritage since 1991 because they are studded with a succession of masterpieces such as Notre- Dame Cathedral, Sainte Chapelle, Louvre, Place de la Concorde, Tour Eiffel, and with prestigious museums: Louvre, Orsay, Quai Branly, Petit Palais…Unfortunately, these banks are crossed by the Pompidou urban motorway, an important and continuous source of atmospheric pollution. The aim of the Project is to evaluate the evolution of the weathering of limestone, glass and stained glass in the centre of Paris in the 21rst century by crossing Climate and Pollution Models with Dose-Response Functions (DRF) for limestone, glass and stained glass and with Climatology of Salt Transitions for limestone. A Lutetian limestone (« Courville Stone ») has been used for the construction and the restoration of the most important monuments (Notre-Dame, Louvre…) and haussmannian buildings in Paris. It has a fine grain, a medium porosity (19%) and contains 90% of CaO. The modern glass of windows and large contemporaneous façades has a Si-Ca-Na composition, it is chemically inert, has a low thermal inertia, a flat surface, no open porosity and no surface roughness, therefore it is very durable. The glass of stained glass windows has a Si-Ca-K composition and it is low durable. Using different climate and pollution scenarios of the 21rst century, the project will evaluate different schemes of material degradations: (i) - Recession of limestone surface; (ii) - Soiling of limestone surface; (iii) - Soiling of modern glass; (iv) - Leaching of ancient stained glass windows; (v) - Deterioration of limestone by salts. The British Hadley Models, the French Météo- France Arpège-Aladin Models and the ENSEMBLES Approach will be crossed with DRF and Climatology of Salts Transitions. An in-the-field inventory (stock at risk) of the surface occupied on the façades by each kind of material (stone, rendering, metal, glass, stained glass…) will be performed. A mapping of the future degradations will be achieved by means of the Aladin-Climat Model (12 x12 km) and Surfex system (1 x 1 km) of Météo-France. The aspect and the state of weathering of the monuments will allow predicting their attractivity and thus the impact on their attendance, which means on cultural and mass tourism in Paris. This assessment will allow to anticipate or to delay the restoration campaigns for the monumental façades. This prestigious part of Paris will be a model for the entire city for the planning of these maintenance campaigns and for estimating their cost, because the results obtained in the centre of Paris will be transposable to all the haussmannian façades, that are made of the same limestone and the same window glass than those studied in the frame of this project, to the large façades in glass of the contemporaneous buildings and to the ancient stained glass windows of the Parisian churches.

Measurement of the Microstructure of Ocean Surface Roughness

DTIC Science & Technology

1996-10-01

ptezmä. fa: paHki 19970303 135 DTIO QUALITY INSPECTED 1 PROCEEDINGS MICROSTRUCTURE SENSORS WORKSHOP 23-25 October 1996 Timberline Lodge , Mt. Hood...Sensors Workshop, 23-25 October 1996, Timberline Lodge , Mt. Hood, Oregon 12a. DISTRIBUTION/AVAILABILITY STATEMENT Approved for public release

Intelligent transportation systems field operational test cross-cutting study : emergency notification and response

DOT National Transportation Integrated Search

2000-08-01

Transportation is vital to the social and economic health of the nation. Surface transportation systems ? the networks of highways, local streets, bus routes, and rail lines ? are the ties that bind communities and facilitate commerce. Despite the fa...

Crystal structure of the receptor-binding domain of botulinum neurotoxin type HA, also known as type FA or H

DOE PAGES

Yao, Guorui; Lam, Kwok-ho; Perry, Kay; ...

2017-03-08

Botulinum neurotoxins (BoNTs), which have been exploited as cosmetics and muscle-disorder treatment medicines for decades, are well known for their extreme neurotoxicity to humans. They pose a potential bioterrorism threat because they cause botulism, a flaccid muscular paralysis-associated disease that requires immediate antitoxin treatment and intensive care over a long period of time. In addition to the existing seven established BoNT serotypes (BoNT/A–G), a new mosaic toxin type termed BoNT/HA (aka type FA or H) was reported recently. Sequence analyses indicate that the receptor-binding domain (HC) of BoNT/HA is ~84% identical to that of BoNT/A1. However, BoNT/HA responds differently tomore » some potent BoNT/A-neutralizing antibodies (e.g., CR2) that target the HC. Therefore, it raises a serious concern as to whether BoNT/HA poses a new threat to our biosecurity. In this study, we report the first high-resolution crystal structure of BoNT/HA-HC at 1.8 Å. Sequence and structure analyses reveal that BoNT/HA and BoNT/A1 are different regarding their binding to cell-surface receptors including both polysialoganglioside (PSG) and synaptic vesicle glycoprotein 2 (SV2). Furthermore, the new structure also provides explanations for the ~540-fold decreased affinity of antibody CR2 towards BoNT/HA compared to BoNT/A1. Altogether, these new findings advance our understanding of the structure and function of this newly identified toxin at the molecular level, and pave the way for the future development of more effective countermeasures.« less

Crystal Structure of the Receptor-Binding Domain of Botulinum Neurotoxin Type HA, Also Known as Type FA or H.

PubMed

Yao, Guorui; Lam, Kwok-Ho; Perry, Kay; Weisemann, Jasmin; Rummel, Andreas; Jin, Rongsheng

2017-03-08

Botulinum neurotoxins (BoNTs), which have been exploited as cosmetics and muscle-disorder treatment medicines for decades, are well known for their extreme neurotoxicity to humans. They pose a potential bioterrorism threat because they cause botulism, a flaccid muscular paralysis-associated disease that requires immediate antitoxin treatment and intensive care over a long period of time. In addition to the existing seven established BoNT serotypes (BoNT/A-G), a new mosaic toxin type termed BoNT/HA (aka type FA or H) was reported recently. Sequence analyses indicate that the receptor-binding domain (H C ) of BoNT/HA is ~84% identical to that of BoNT/A1. However, BoNT/HA responds differently to some potent BoNT/A-neutralizing antibodies (e.g., CR2) that target the H C . Therefore, it raises a serious concern as to whether BoNT/HA poses a new threat to our biosecurity. In this study, we report the first high-resolution crystal structure of BoNT/HA-H C at 1.8 Å. Sequence and structure analyses reveal that BoNT/HA and BoNT/A1 are different regarding their binding to cell-surface receptors including both polysialoganglioside (PSG) and synaptic vesicle glycoprotein 2 (SV2). Furthermore, the new structure also provides explanations for the ~540-fold decreased affinity of antibody CR2 towards BoNT/HA compared to BoNT/A1. Taken together, these new findings advance our understanding of the structure and function of this newly identified toxin at the molecular level, and pave the way for the future development of more effective countermeasures.

Crystal structure of the receptor-binding domain of botulinum neurotoxin type HA, also known as type FA or H

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

Yao, Guorui; Lam, Kwok-ho; Perry, Kay

Botulinum neurotoxins (BoNTs), which have been exploited as cosmetics and muscle-disorder treatment medicines for decades, are well known for their extreme neurotoxicity to humans. They pose a potential bioterrorism threat because they cause botulism, a flaccid muscular paralysis-associated disease that requires immediate antitoxin treatment and intensive care over a long period of time. In addition to the existing seven established BoNT serotypes (BoNT/A–G), a new mosaic toxin type termed BoNT/HA (aka type FA or H) was reported recently. Sequence analyses indicate that the receptor-binding domain (HC) of BoNT/HA is ~84% identical to that of BoNT/A1. However, BoNT/HA responds differently tomore » some potent BoNT/A-neutralizing antibodies (e.g., CR2) that target the HC. Therefore, it raises a serious concern as to whether BoNT/HA poses a new threat to our biosecurity. In this study, we report the first high-resolution crystal structure of BoNT/HA-HC at 1.8 Å. Sequence and structure analyses reveal that BoNT/HA and BoNT/A1 are different regarding their binding to cell-surface receptors including both polysialoganglioside (PSG) and synaptic vesicle glycoprotein 2 (SV2). Furthermore, the new structure also provides explanations for the ~540-fold decreased affinity of antibody CR2 towards BoNT/HA compared to BoNT/A1. Altogether, these new findings advance our understanding of the structure and function of this newly identified toxin at the molecular level, and pave the way for the future development of more effective countermeasures.« less

Fatty acid composition at the base of aquatic food webs is influenced by habitat type and watershed land use.

PubMed

Larson, James H; Richardson, William B; Knights, Brent C; Bartsch, Lynn A; Bartsch, Michelle R; Nelson, John C; Veldboom, Jason A; Vallazza, Jon M

2013-01-01

Spatial variation in food resources strongly influences many aspects of aquatic consumer ecology. Although large-scale controls over spatial variation in many aspects of food resources are well known, others have received little study. Here we investigated variation in the fatty acid (FA) composition of seston and primary consumers within (i.e., among habitats) and among tributary systems of Lake Michigan, USA. FA composition of food is important because all metazoans require certain FAs for proper growth and development that cannot be produced de novo, including many polyunsaturated fatty acids (PUFAs). Here we sampled three habitat types (river, rivermouth and nearshore zone) in 11 tributaries of Lake Michigan to assess the amount of FA in seston and primary consumers of seston. We hypothesize that among-system and among-habitat variation in FAs at the base of food webs would be related to algal production, which in turn is influenced by three land cover characteristics: 1) combined agriculture and urban lands (an indication of anthropogenic nutrient inputs that fuel algal production), 2) the proportion of surface waters (an indication of water residence times that allow algal producers to accumulate) and 3) the extent of riparian forested buffers (an indication of stream shading that reduces algal production). Of these three land cover characteristics, only intense land use appeared to strongly related to seston and consumer FA and this effect was only strong in rivermouth and nearshore lake sites. River seston and consumer FA composition was highly variable, but that variation does not appear to be driven by the watershed land cover characteristics investigated here. Whether the spatial variation in FA content at the base of these food webs significantly influences the production of economically important species higher in the food web should be a focus of future research.

Fatty acid composition at the base of aquatic food webs is influenced by habitat type and watershed land use

USGS Publications Warehouse

Larson, James H.; Richardson, William B.; Knights, Brent C.; Bartsch, Lynn; Bartsch, Michelle; Nelson, J. C.; Veldboom, Jason A.; Vallazza, Jonathan M.

2013-01-01

Spatial variation in food resources strongly influences many aspects of aquatic consumer ecology. Although large-scale controls over spatial variation in many aspects of food resources are well known, others have received little study. Here we investigated variation in the fatty acid (FA) composition of seston and primary consumers within (i.e., among habitats) and among tributary systems of Lake Michigan, USA. FA composition of food is important because all metazoans require certain FAs for proper growth and development that cannot be produced de novo, including many polyunsaturated fatty acids (PUFAs). Here we sampled three habitat types (river, rivermouth and nearshore zone) in 11 tributaries of Lake Michigan to assess the amount of FA in seston and primary consumers of seston. We hypothesize that among-system and among-habitat variation in FAs at the base of food webs would be related to algal production, which in turn is influenced by three land cover characteristics: 1) combined agriculture and urban lands (an indication of anthropogenic nutrient inputs that fuel algal production), 2) the proportion of surface waters (an indication of water residence times that allow algal producers to accumulate) and 3) the extent of riparian forested buffers (an indication of stream shading that reduces algal production). Of these three land cover characteristics, only intense land use appeared to strongly related to seston and consumer FA and this effect was only strong in rivermouth and nearshore lake sites. River seston and consumer FA composition was highly variable, but that variation does not appear to be driven by the watershed land cover characteristics investigated here. Whether the spatial variation in FA content at the base of these food webs significantly influences the production of economically important species higher in the food web should be a focus of future research.

A field-assisted moderator for low-energy positron beams

NASA Astrophysics Data System (ADS)

Beling, C. D.; Simpson, R. I.; Charlton, M.; Jacobsen, F. M.; Griffith, T. C.; Moriarty, P.; Fung, S.

1987-01-01

A new positron field-assisted (FA) moderator based on the drift of positrons across a cooled silicon crystal is proposed. Using estimates for both the β + implantation profile and attainable drift velocities, the efficiency of drift to a slow e+ emitting surface is calculated using a diffusion equation which incorporates terms describing positron drift and annihilation. It is conjectured that efficiencies of up to 10% can be achieved. The use of epitaxially grown metallic suicide contacts to facilitate the application of the electric field is described and the consequences of using such contacts are fully discussed. Applications of the FA transmission mode moderator described here to produce timed brightness enhanced beams are briefly discussed.

Oral Omega-3 Fatty Acid Supplementation for Laser In Situ Keratomileusis-Associated Dry Eye.

PubMed

Goyal, Parul; Jain, Arun K; Malhotra, Chintan

2017-02-01

To determine the effect of oral omega-3 fatty acid (ω3FA) supplementation in laser in situ keratomileusis (LASIK)-associated dry eye. In this prospective, open-label study, patients undergoing LASIK were randomized to receive either 1.2 g/d of a triglyceride formulation of oral ω3FA (treatment group) or 400 mg/d vitamin E (control group) for 1 week before and continued for 12 weeks after surgery. Ocular surface disease index, tear breakup time, ocular surface staining, and Schirmer scores were evaluated and compared preoperatively and at 3 months after LASIK. The study included 30 patients in each group. All parameters were comparable at baseline. Ocular surface disease index scores increased comparably in both groups (1.9 ± 0.6 increase in the treatment group; 2.8 ± 0.5 in the control group) (P = 0.267). Compared with baseline levels, tear breakup time decreased significantly (P < 0.01) but comparably in both treatment (-2.3 ± 0.4 seconds decrease) and control (-3.5 ± 0.7 seconds decrease) groups (P = 0.105). More eyes in the control group (43.4%) had conjunctival staining with Lissamine green at 3 months compared with the treatment group (14%) (P = 0.009). The Schirmer score at 3 months was higher (P = 0.003) in the treatment group (30.5 ± 0.90 mm) than in the control group (25.7 ± 1.3 mm) with a increase of 5.9 ± 1.3 mm from baseline in the treatment group and a decrease of 1.5 ± 1.2 mm in the control group. Supplementation with ω3FA in patients undergoing LASIK had a positive influence on tear secretion, whereas tear film stability remained unaffected when compared with the control group.

Grain-based versus alfalfa-based subacute ruminal acidosis induction experiments: Similarities and differences between changes in milk fatty acids.

PubMed

Colman, E; Khafipour, E; Vlaeminck, B; De Baets, B; Plaizier, J C; Fievez, V

2013-07-01

Subacute ruminal acidosis (SARA) is one of the most important metabolic disorders, traditionally characterized by low rumen pH, which might be induced by an increase in the dietary proportion of grains as well as by a reduction of structural fiber. Both approaches were used in earlier published experiments in which SARA was induced by replacing part of the ration by a grain mixture or alfalfa hay by alfalfa pellets. The main differences between both experiments were the presence of blood lipopolysaccharide and Escherichia coli and associated effects on the rumen microbial population in the rumen of grain-based induced SARA animals as well as a great amount of quickly fermentable carbohydrates in the grain-based SARA induction experiment. Both induction approaches changed rumen pH although the pH decrease was more substantial in the alfalfa-based SARA induction protocol. The goal of the current analysis was to assess whether both acidosis induction approaches provoked similar shifts in the milk fatty acid (FA) profile. Similar changes of the odd- and branched-chain FA and the C18 biohydrogenation intermediates were observed in the alfalfa-based SARA induction experiment and the grain-based SARA induction experiment, although they were more pronounced in the former. The proportion of trans-10 C18:1 in the last week of the alfalfa-based induction experiment was 6 times higher than the proportion measured during the control week. The main difference between both induction experiments under similar rumen pH changes was the decreasing sum of iso FA during the grain-based SARA induction experiment whereas the sum of iso FA remained stable during the alfalfa-based SARA induction experiment. The cellulolytic bacterial community seemed to be negatively affected by either the presence of E. coli and the associated lipopolysaccharide accumulation in the rumen or by the amount of starch and quickly fermentable carbohydrates in the diet. In general, changes in the milk FA profile were related to changes in rumen pH. Nevertheless, feed characteristics (low in structural fiber vs. high in starch) also affected the milk FA profile and, as such, both effects should be taken into account when subacute acidosis occurs. Copyright © 2013 American Dairy Science Association. Published by Elsevier Inc. All rights reserved.

Diffusion tensor imaging and diffusion tensor imaging-fibre tractograph depict the mechanisms of Broca-like and Wernicke-like conduction aphasia.

PubMed

Song, Xinjie; Dornbos, David; Lai, Zongli; Zhang, Yumei; Li, Tieshan; Chen, Hongyan; Yang, Zhonghua

2011-06-01

Conduction aphasia is usually considered a result of damage of the arcuate fasciculus, which is subjacent to the parietal portion of the supra-marginal gyrus and the upper part of the insula. It is important to stress that many features of conduction aphasia relate to a cortical deficit, more than a pure disconnection mechanism. In this study, we explore the mechanism of Broca-like and Wernicke-like conduction aphasia by using diffusion tensor imaging (DTI) and diffusion tensor imaging-fibre tractograph (DT-FT). We enrolled five Broca-like conduction aphasia cases, five Wernicke-like aphasia conduction cases and 10 healthy volunteers residing in Beijing and speaking Mandarin. All are right handed. We analyzed the arcuate fasciculus, Broca's areas and Wernicke's areas by DTI and measured fractional anisotrogy (FA). The results of left and right hemispheres were compared in both conduction aphasia cases and volunteers. Then the results of the conduction aphasia cases were compared with those of volunteers. The fibre construction of Broca's and Wernicke's areas was also compared by DTI-FT. The FA occupied by the identified connective pathways (Broca's area, Wernicke's area and the arcuate fasciculus) in the left hemisphere was larger than that in the right hemisphere in the control group (P<0.05). Among Broca-like conduction aphasia cases, the FA of the left Broca's area was smaller than that of the right mirror side (P<0.05), and the FA of the left anterior segment of the arcuate fasciculus was smaller than that of right mirror side (P<0.05). On the other hand, among Wernicke-like conduction aphasia patients, the FA of the left Wernicke's area was smaller than that of right mirror side (P<0.05), and the FA of left posterior segment of arcuate fasciculus was smaller than that of right mirror side (P<0.05). Conduction aphasia results from not only arcuate fasciculus destruction, but also from disruption of the associated cortical areas. Along different segments of the arcuate fasciculus, the characteristics of language disorders of conduction aphasia were different. A lesion involving Broca's area and the anterior segments of the arcuate fasciculus would lead to Broca-like conduction aphasia, whereas a lesion involved Wernicke's area and posterior segments of the arcuate fasciculus would lead to Wernicke-like conduction aphasia.

Abnormal white matter properties in adolescent girls with anorexia nervosa

PubMed Central

Travis, Katherine E.; Golden, Neville H.; Feldman, Heidi M.; Solomon, Murray; Nguyen, Jenny; Mezer, Aviv; Yeatman, Jason D.; Dougherty, Robert F.

2015-01-01

Anorexia nervosa (AN) is a serious eating disorder that typically emerges during adolescence and occurs most frequently in females. To date, very few studies have investigated the possible impact of AN on white matter tissue properties during adolescence, when white matter is still developing. The present study evaluated white matter tissue properties in adolescent girls with AN using diffusion MRI with tractography and T1 relaxometry to measure R1 (1/T1), an index of myelin content. Fifteen adolescent girls with AN (mean age = 16.6 years ± 1.4) were compared to fifteen age-matched girls with normal weight and eating behaviors (mean age = 17.1 years ± 1.3). We identified and segmented 9 bilateral cerebral tracts (18) and 8 callosal fiber tracts in each participant's brain (26 total). Tract profiles were generated by computing measures for fractional anisotropy (FA) and R1 along the trajectory of each tract. Compared to controls, FA in the AN group was significantly decreased in 4 of 26 white matter tracts and significantly increased in 2 of 26 white matter tracts. R1 was significantly decreased in the AN group compared to controls in 11 of 26 white matter tracts. Reduced FA in combination with reduced R1 suggests that the observed white matter differences in AN are likely due to reductions in myelin content. For the majority of tracts, group differences in FA and R1 did not occur within the same tract. The present findings have important implications for understanding the neurobiological factors underlying white matter changes associated with AN and invite further investigations examining associations between white matter properties and specific physiological, cognitive, social, or emotional functions affected in AN. PMID:26740918

A subset of sweet-sensing neurons identified by IR56d are necessary and sufficient for fatty acid taste.

PubMed

Tauber, John M; Brown, Elizabeth B; Li, Yuanyuan; Yurgel, Maria E; Masek, Pavel; Keene, Alex C

2017-11-01

Fat represents a calorically potent food source that yields approximately twice the amount of energy as carbohydrates or proteins per unit of mass. The highly palatable taste of free fatty acids (FAs), one of the building blocks of fat, promotes food consumption, activates reward circuitry, and is thought to contribute to hedonic feeding underlying many metabolism-related disorders. Despite a role in the etiology of metabolic diseases, little is known about how dietary fats are detected by the gustatory system to promote feeding. Previously, we showed that a broad population of sugar-sensing taste neurons expressing Gustatory Receptor 64f (Gr64f) is required for reflexive feeding responses to both FAs and sugars. Here, we report a genetic silencing screen to identify specific populations of taste neurons that mediate fatty acid (FA) taste. We find neurons identified by expression of Ionotropic Receptor 56d (IR56d) are necessary and sufficient for reflexive feeding response to FAs. Functional imaging reveals that IR56d-expressing neurons are responsive to short- and medium-chain FAs. Silencing IR56d neurons selectively abolishes FA taste, and their activation is sufficient to drive feeding responses. Analysis of co-expression with Gr64f identifies two subpopulations of IR56d-expressing neurons. While physiological imaging reveals that both populations are responsive to FAs, IR56d/Gr64f neurons are activated by medium-chain FAs and are sufficient for reflexive feeding response to FAs. Moreover, flies can discriminate between sugar and FAs in an aversive taste memory assay, indicating that FA taste is a unique modality in Drosophila. Taken together, these findings localize FA taste within the Drosophila gustatory center and provide an opportunity to investigate discrimination between different categories of appetitive tastants.

Evaluating the relationship between white matter integrity, cognition, and varieties of video game learning.

PubMed

Ray, Nicholas R; O'Connell, Margaret A; Nashiro, Kaoru; Smith, Evan T; Qin, Shuo; Basak, Chandramallika

2017-01-01

Many studies are currently researching the effects of video games, particularly in the domain of cognitive training. Great variability exists among video games however, and few studies have attempted to compare different types of video games. Little is known, for instance, about the cognitive processes or brain structures that underlie learning of different genres of video games. To examine the cognitive and neural underpinnings of two different types of game learning in order to evaluate their common and separate correlates, with the hopes of informing future intervention research. Participants (31 younger adults and 31 older adults) completed an extensive cognitive battery and played two different genres of video games, one action game and one strategy game, for 1.5 hours each. DTI scans were acquired for each participant, and regional fractional anisotropy (FA) values were extracted using the JHU atlas. Behavioral results indicated that better performance on tasks of working memory and perceptual discrimination was related to enhanced learning in both games, even after controlling for age, whereas better performance on a perceptual speed task was uniquely related with enhanced learning of the strategy game. DTI results indicated that white matter FA in the right fornix/stria terminalis was correlated with action game learning, whereas white matter FA in the left cingulum/hippocampus was correlated with strategy game learning, even after controlling for age. Although cognition, to a large extent, was a common predictor of both types of game learning, regional white matter FA could separately predict action and strategy game learning. Given the neural and cognitive correlates of strategy game learning, strategy games may provide a more beneficial training tool for adults suffering from memory-related disorders or declines in processing speed, particularly older adults.

Early Imaging and Adverse Neurodevelopmental Outcome in Asphyxiated Newborns Treated With Hypothermia.

PubMed

Al Amrani, Fatema; Kwan, Saskia; Gilbert, Guillaume; Saint-Martin, Christine; Shevell, Michael; Wintermark, Pia

2017-08-01

Brain injury can be identified as early as day two of life in asphyxiated newborns treated with hypothermia, when using diffusion magnetic resonance imaging (MRI). However, it remains unclear whether these diffusion changes can predict future neurodevelopment. This study aimed to determine whether abnormal early diffusion changes in newborns treated with hypothermia are associated with adverse neurodevelopmental outcome at age two years. Asphyxiated newborns treated with hypothermia were enrolled prospectively. They underwent magnetic resonance imaging (MRI) at specific time points over the first month of life, including diffusion-weighted imaging and diffusion-tensor imaging. Apparent diffusion coefficient (ADC) and fractional anisotropy (FA) values were measured in different regions of interest. Adverse neurodevelopmental outcome was defined as cerebral palsy, global developmental delay, and/or seizure disorder around age two years. ADC and FA values were compared between the newborns developing or not developing adverse outcome. Twenty-nine asphyxiated newborns treated with hypothermia were included. Among the newborns developing adverse outcome, ADC values were significantly decreased on days two to three of life and increased around day ten of life in the thalamus, posterior limb of the internal capsule, and the lentiform nucleus. FA values decreased in the same regions around day 30 of life. These newborns also had increased ADC around day ten of life and around day 30 of life, and decreased FA around day 30 of life in the anterior and posterior white matter. Diffusion changes that were evident as early as day two of life, when the asphyxiated newborns were still treated with hypothermia, were associated with later abnormal neurodevelopmental outcome. Copyright © 2017 Elsevier Inc. All rights reserved.

White matter microstructural changes as vulnerability factors and acquired signs of post-earthquake distress.

PubMed

Sekiguchi, Atsushi; Sugiura, Motoaki; Taki, Yasuyuki; Kotozaki, Yuka; Nouchi, Rui; Takeuchi, Hikaru; Araki, Tsuyoshi; Hanawa, Sugiko; Nakagawa, Seishu; Miyauchi, Carlos Makoto; Sakuma, Atsushi; Kawashima, Ryuta

2014-01-01

Many survivors of severe disasters need psychological support, even those not suffering post-traumatic stress disorder (PTSD). The critical issue in understanding the psychological response after experiencing severe disasters is to distinguish neurological microstructural underpinnings as vulnerability factors from signs of emotional distress acquired soon after the stressful life event. We collected diffusion-tensor magnetic resonance imaging (DTI) data from a group of healthy adolescents before the Great East Japan Earthquake and re-examined the DTIs and anxiety levels of 30 non-PTSD subjects from this group 3-4 months after the earthquake using voxel-based analyses in a longitudinal DTI study before and after the earthquake. We found that the state anxiety level after the earthquake was negatively associated with fractional anisotropy (FA) in the right anterior cingulum (Cg) before the earthquake (r = -0.61, voxel level p<0.0025, cluster level p<0.05 corrected), and positively associated with increased FA changes from before to after the earthquake in the left anterior Cg (r = 0.70, voxel level p<0.0025, cluster level p<0.05 corrected) and uncinate fasciculus (Uf) (r = 0.65, voxel level p<0.0025, cluster level p<0.05 corrected). The results demonstrated that lower FA in the right anterior Cg was a vulnerability factor and increased FA in the left anterior Cg and Uf was an acquired sign of state anxiety after the earthquake. We postulate that subjects with dysfunctions in processing fear and anxiety before the disaster were likely to have higher anxiety levels requiring frequent emotional regulation after the disaster. These findings provide new evidence of psychophysiological responses at the neural network level soon after a stressful life event and might contribute to the development of effective methods to prevent PTSD.

Exploring the relationship between white matter and gray matter damage in early primary progressive multiple sclerosis: an in vivo study with TBSS and VBM.

PubMed

Bodini, Benedetta; Khaleeli, Zhaleh; Cercignani, Mara; Miller, David H; Thompson, Alan J; Ciccarelli, Olga

2009-09-01

We investigated the relationship between the damage occurring in the brain normal-appearing white matter (NAWM) and in the gray matter (GM) in patients with early Primary Progressive multiple sclerosis (PPMS), using Tract-Based Spatial Statistics (TBSS) and an optimized voxel-based morphometry (VBM) approach. Thirty-five patients with early PPMS underwent diffusion tensor and conventional imaging and were clinically assessed. TBSS and VBM were employed to localize regions of lower fractional anisotropy (FA) and lower GM volume in patients compared with controls. Areas of anatomical and quantitative correlation between NAWM and GM damage were detected. Multiple regression analyses were performed to investigate whether NAWM FA or GM volume of regions correlated with clinical scores independently from the other and from age and gender. In patients, we found 11 brain regions that showed an anatomical correspondence between reduced NAWM FA and GM atrophy; of these, four showed a quantitative correlation (i.e., the right sensory motor region with the adjacent corticospinal tract, the left and right thalamus with the corresponding thalamic radiations and the left insula with the adjacent WM). Either the NAWM FA or the GM volume in each of these regions correlated with disability. These results demonstrate a link between the pathological processes occurring in the NAWM and in the GM in PPMS in specific, clinically relevant brain areas. Longitudinal studies will determine whether the GM atrophy precedes or follows the NAWM damage. The methodology that we described may be useful to investigate other neurological disorders affecting both the WM and the GM. 2009 Wiley-Liss, Inc.

FANCG promotes formation of a newly identified protein complex containing BRCA2, FANCD2 and XRCC3.

PubMed

Wilson, J B; Yamamoto, K; Marriott, A S; Hussain, S; Sung, P; Hoatlin, M E; Mathew, C G; Takata, M; Thompson, L H; Kupfer, G M; Jones, N J

2008-06-12

Fanconi anemia (FA) is a human disorder characterized by cancer susceptibility and cellular sensitivity to DNA crosslinks and other damages. Thirteen complementation groups and genes are identified, including BRCA2, which is defective in the FA-D1 group. Eight of the FA proteins, including FANCG, participate in a nuclear core complex that is required for the monoubiquitylation of FANCD2 and FANCI. FANCD2, like FANCD1/BRCA2, is not part of the core complex, and we previously showed direct BRCA2-FANCD2 interaction using yeast two-hybrid analysis. We now show in human and hamster cells that expression of FANCG protein, but not the other core complex proteins, is required for co-precipitation of BRCA2 and FANCD2. We also show that phosphorylation of FANCG serine 7 is required for its co-precipitation with BRCA2, XRCC3 and FANCD2, as well as the direct interaction of BRCA2-FANCD2. These results argue that FANCG has a role independent of the FA core complex, and we propose that phosphorylation of serine 7 is the signalling event required for forming a discrete complex comprising FANCD1/BRCA2-FANCD2-FANCG-XRCC3 (D1-D2-G-X3). Cells that fail to express either phospho-Ser7-FANCG, or full length BRCA2 protein, lack the interactions amongst the four component proteins. A role for D1-D2-G-X3 in homologous recombination repair (HRR) is supported by our finding that FANCG and the RAD51-paralog XRCC3 are epistatic for sensitivity to DNA crosslinking compounds in DT40 chicken cells. Our findings further define the intricate interface between FANC and HRR proteins in maintaining chromosome stability.

White matter developmental trajectories associated with persistence and recovery of childhood stuttering.

PubMed

Chow, Ho Ming; Chang, Soo-Eun

2017-04-08

Stuttering affects the fundamental human ability of fluent speech production, and can have a significant negative impact on an individual's psychosocial development. While the disorder affects about 5% of all preschool children, approximately 80% of them recover naturally within a few years of stuttering onset. The pathophysiology and neuroanatomical development trajectories associated with persistence and recovery of stuttering are still largely unknown. Here, the first mixed longitudinal diffusion tensor imaging (DTI) study of childhood stuttering has been reported. A total of 195 high quality DTI scans from 35 children who stutter (CWS) and 43 controls between 3 and 12 years of age were acquired, with an average of three scans per child, each collected approximately a year apart. Fractional anisotropy (FA), a measure reflecting white matter structural coherence, was analyzed voxel-wise to examine group and age-related differences using a linear mixed-effects (LME) model. Results showed that CWS exhibited decreased FA relative to controls in the left arcuate fasciculus, underlying the inferior parietal and posterior temporal areas, and the mid body of corpus callosum. Further, white matter developmental trajectories reflecting growth rate of these tract regions differentiated children with persistent stuttering from those who recovered from stuttering. Specifically, a reduction in FA growth rate (i.e., slower FA growth with age) in persistent children relative to fluent controls in the left arcuate fasciculus and corpus callosum was found, which was not evident in recovered children. These findings provide first glimpses into the possible neural mechanisms of onset, persistence, and recovery of childhood stuttering. Hum Brain Mapp, 2017. © 2017 Wiley Periodicals, Inc. © 2017 Wiley Periodicals, Inc.

White matter microstructure alterations correlate with terminally differentiated CD8+ effector T cell depletion in the peripheral blood in mania: Combined DTI and immunological investigation in the different phases of bipolar disorder.

PubMed

Magioncalda, Paola; Martino, Matteo; Tardito, Samuele; Sterlini, Bruno; Conio, Benedetta; Marozzi, Valentina; Adavastro, Giulia; Capobianco, Laura; Russo, Daniel; Parodi, Alessia; Kalli, Francesca; Nasi, Giorgia; Altosole, Tiziana; Piaggio, Niccolò; Northoff, Georg; Fenoglio, Daniela; Inglese, Matilde; Filaci, Gilberto; Amore, Mario

2018-05-01

White matter (WM) microstructural abnormalities and, independently, signs of immunological activation were consistently demonstrated in bipolar disorder (BD). However, the relationship between WM and immunological alterations as well as their occurrence in the various phases of BD remain unclear. In 60 type I BD patients - 20 in manic, 20 in depressive, 20 in euthymic phases - and 20 controls we investigated: (i) diffusion tensor imaging (DTI)-derived fractional anisotropy (FA), radial diffusivity (RD) and axial diffusivity (AD) using a tract-based spatial statistics (TBSS) approach; (ii) circulating T cell subpopulations frequencies, as well as plasma levels of different cytokines; (iii) potential relationships between WM and immunological data. We found: (i) a significant widespread combined FA-RD alteration mainly in mania, with involvement of the body of corpus callosum (BCC) and superior corona radiata (SCR); (ii) significant increase in CD4+ T cells as well as significant decrease in CD8+ T cells and their subpopulations effector memory (CD8+ CD28-CD45RA-), terminal effector memory (CD8+ CD28-CD45RA+) and CD8+ IFNγ+ in mania; (iii) a significant relationship between WM and immunological alterations in the whole cohort, and a significant correlation of FA-RD abnormalities in the BCC and SCR with reduced frequencies of CD8+ terminal effector memory and CD8+ IFNγ+ T cells in mania only. Our data show a combined occurrence of WM and immunological alterations in mania. WM abnormalities highly correlated with reduction in circulating CD8+ T cell subpopulations that are terminally differentiated effector cells prone to tissue migration, suggesting that these T cells could play a role in WM alteration in BD. Copyright © 2018 Elsevier Inc. All rights reserved.

Matrix mechanics controls FHL2 movement to the nucleus to activate p21 expression

PubMed Central

Nakazawa, Naotaka; Sathe, Aneesh R.; Shivashankar, G. V.; Sheetz, Michael P.

2016-01-01

Substrate rigidity affects many physiological processes through mechanochemical signals from focal adhesion (FA) complexes that subsequently modulate gene expression. We find that shuttling of the LIM domain (domain discovered in the proteins, Lin11, Isl-1, and Mec-3) protein four-and-a-half LIM domains 2 (FHL2) between FAs and the nucleus depends on matrix mechanics. In particular, on soft surfaces or after the loss of force, FHL2 moves from FAs into the nucleus and concentrates at RNA polymerase (Pol) II sites, where it acts as a transcriptional cofactor, causing an increase in p21 gene expression that will inhibit growth on soft surfaces. At the molecular level, shuttling requires a specific tyrosine in FHL2, as well as phosphorylation by active FA kinase (FAK). Thus, we suggest that FHL2 phosphorylation by FAK is a critical, mechanically dependent step in signaling from soft matrices to the nucleus to inhibit cell proliferation by increasing p21 expression. PMID:27742790

Interactions between stepwise-eluted sub-fractions of fulvic acids and protons revealed by fluorescence titration combined with EEM-PARAFAC.

PubMed

Song, Fanhao; Wu, Fengchang; Guo, Fei; Wang, Hao; Feng, Weiying; Zhou, Min; Deng, Yanghui; Bai, Yingchen; Xing, Baoshan; Giesy, John P

2017-12-15

In aquatic environments, pH can control environmental behaviors of fulvic acid (FA) via regulating hydrolysis of functional groups. Sub-fractions of FA, eluted using pyrophosphate buffers with initial pHs of 3.0 (FA 3 ), 5.0 (FA 5 ), 7.0 (FA 7 ), 9.0 (FA 9 ) and 13.0 (FA 13 ), were used to explore interactions between the various, operationally defined, FA fractions and protons, by use of EEM-PARAFAC analysis. Splitting of peaks (FA 3 and FA 13 ), merging of peaks (FA 7 ), disappearance of peaks (FA 9 and FA 13 ), and red/blue-shifting of peaks were observed during fluorescence titration. Fulvic-like components were identified from FA 3 -FA 13 , and protein-like components were observed in fractions FA 9 and FA 13 . There primary compounds (carboxylic-like, phenolic-like, and protein-like chromophores) in PARAFAC components were distinguished based on acid-base properties. Dissociation constants (pK a ) for fulvic-like components with proton ranged from 2.43 to 4.13 in an acidic pH and from 9.95 to 11.27 at basic pH. These results might be due to protonation of di-carboxylate and phenolic functional groups. At basic pH, pK a values of protein-like components (9.77-10.13) were similar to those of amino acids. However, at acidic pH, pK a values of protein-like components, which ranged from 3.33 to 4.22, were 1-2units greater than those of amino acids. Results presented here, will benefit understanding of environmental behaviors of FA, as well as interactions of FA with environmental contaminants. Copyright © 2017 Elsevier B.V. All rights reserved.

Starmerella camargoi f.a., sp. nov., Starmerella ilheusensis f.a., sp. nov., Starmerella litoralis f.a., sp. nov., Starmerella opuntiae f.a., sp. nov., Starmerella roubikii f.a., sp. nov. and Starmerella vitae f.a., sp. nov., isolated from flowers and bees, and transfer of related Candida species to the genus Starmerella as new combinations.

PubMed

Santos, Ana Raquel O; Leon, Marina P; Barros, Katharina O; Freitas, Larissa F D; Hughes, Alice F S; Morais, Paula B; Lachance, Marc-André; Rosa, Carlos A

2018-04-01

Six novel yeast species, Starmerella camargoi f.a., sp. nov., Starmerella ilheusensis f.a., sp. nov., Starmerella litoralis f.a., Starmerella opuntiae f.a., sp. nov., sp. nov., Starmerella roubikii f.a., sp. nov. and Starmerella vitae f.a, sp. nov. are proposed to accommodate 19 isolates recovered from ephemeral flowers or bees in Brazil, Costa Rica and Belize. Sequence analysis of the ITS-5.8S region (when available) and the D1/D2 domains of the large subunit of the rRNA gene showed that the six novel yeasts are phylogenetically related to several species of the Starmerella clade. The type strains are Starmerella camargoi f.a., sp. nov. UFMG-CM-Y595 T (=CBS 14130 T ; Mycobank number MB 822640), Starmerella ilheusensis f.a., sp. nov. UFMG-CM-Y596 T (=CBS CBS14131 T ; MB 822641), Starmerella litoralis f.a., sp. nov. UFMG-CM-Y603 T (=CBS14104 T ; MB 822642), Starmerella opuntiae f.a., sp. nov. UFMG-CM-Y286 T (=CBS 13466 T ; MB 822643), Starmerella roubikii f.a., sp. nov. UWOPS 01-191.1 (=CBS 15148; MB 822645) and Starmerella vitae f.a., sp. nov. UWOPS 00-107.2 (=CBS 15147 T ; MB 822646). In addition, 25 species currently assigned to the genus Candida are reassigned formally to the genus Starmerella.

Prismatic louver active façades for natural illumination and thermal energy gain in high-rise and commercial buildings

NASA Astrophysics Data System (ADS)

Vlachokostas, A.; Volkmann, C.; Madamopoulos, N.

2013-06-01

High-rise and commercial buildings in urban centers present a great challenge in terms of their energy consumption. Due to maximization of rentable square footage, the preferred urban façade system over the past 50 years has been the "curtain wall", only a few inches thick and comprised of modular steel or aluminum framing and predominant glass infills. The perceived Achilles heel of these modern glass façade systems is their thermal inefficiency: They are inadequate thermal barriers and exhibit excessive solar gain. The excessive solar gain has a negative impact on lighting and cooling loads of the entire building. This negative impact will be further exacerbated with rising energy costs. However, rather than view the glass façade's uncontrolled solar gain merely as a weakness contributing to higher energy consumption, the condition could indeed be considered as related to an energy solution. These glass façades can be retrofitted to operate as a provider of daylight and energy for the rest of the building, taking advantage of the overexposure to the sun. With today's technology, the sun's abundant renewable energy can be the driving force for the energy transition of these building envelopes. Illumination, thermal energy, and electricity production can be directly supplied from the sun, and when correctly and efficiently managed, they can lead to a significantly less energy-intensive building stock. We propose a multi-purpose, prismatic, louver-based façade to perform both daylight and thermal energy harvesting with a goal of offering a better daylight environment for the occupants, and reduce the energy consumption and carbon footprint of the building. While decentralized air-conditioning units are commonly accepted as façade "plug-ins", such decentralization could be utilized with more benefits by passively managing the interior space conditions, without using any extra power. Just as living organisms respond and adapt to the environmental changes in their surroundings, the proposed multi-purpose prismatic louver façade can be responsive and resilient to daytime sky conditions, environmental temperatures and occupant needs by exploiting options presented by the three sides of the prismatic louvers. The façade is highly configurable since every side of the prismatic louver façade can perform a different operation. The prism itself operates as a redirector of sunlight from the glass façade to the ceiling and consequently diffuses the sunlight throughout the room, providing higher and more uniform illumination levels. In addition, each side of the prismatic louver can be implemented in multiple ways (e.g., visibly transparent photovoltaic cells, luminescent solar concentrators). The ability to rotate the prismatic louvers along their axes allows the user to expose a set of different surfaces to the sun's radiation in accordance with different climatic conditions and occupant needs. Thus, the prismatic louvers help achieve a selective control and management of the incoming light that allows us to manipulate the incoming energy for the benefit of the building and its occupants.

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

PubMed

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

2013-01-01

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

Ab initio study of potential ultrafast internal conversion routes in oxybenzone, caffeic acid, and ferulic acid: implications for sunscreens.

PubMed

Karsili, Tolga N V; Marchetti, Barbara; Ashfold, Michael N R; Domcke, Wolfgang

2014-12-26

Oxybenzone (OB) and ferulic acid (FA) both find use in commercial sunscreens; caffeic acid (CA) differs from FA by virtue of an -OH group in place of a -OCH3 group on the aromatic ring. We report the results of ab initio calculations designed to explore the excited state nonradiative relaxation pathways that provide photostability to these molecules and the photoprotection they offer toward UV-A and UV-B radiation. In the case of OB, internal conversion (IC) is deduced to occur on ultrafast time scales, via a barrierless electron-driven H atom transfer pathway from the S1(1(1)nπ*) state to a conical intersection (CI) with the ground (S0) state potential energy surface (PES). The situation with respect to CA and FA is somewhat less clear-cut, with low energy CIs identified by linking excited states to the S0 state following photoexcitation and subsequent evolution along (i) a ring centered out-of-plane deformation coordinate, (ii) the E/Z isomerism coordinate and, in the case of CA, (iii) an O-H stretch coordinate. Analogy with catechol suggests that the last of these processes (if active) would lead to radical formation (and thus potential phototoxicity), encouraging a suggestion that FA might be superior to CA as a sunscreen ingredient.

Ionic complexation as a non-covalent approach for the design of folate anchored rifampicin Gantrez nanoparticles.

PubMed

Date, Praveen V; Patel, Mitesh D; Majee, Sharmila B; Samad, Abdul; Devarajan, Padma V

2013-05-01

The present study discloses the design of folate anchored Rifampicin-Poly methylvinylether maleic anhydride copolymer (Gantrez AN-119, Gantrez) nanoparticles (RFMGzFa) by ionic complexation. Folic acid was anchored to the preformed drug loaded nanoparticles. Folic acid was anchored in different concentration by simply varying the amount of folic acid added during preparation. RFMGzFa nanoparticles were prepared by emulsion solvent diffusion method. Gantrez AN-119 rapidly hydrolyzes in aqueous medium releasing carboxylic acid groups, to create an acidic environment. This facilitates protonation and subsequent ionic complexation of folic acid with the carboxylic groups, to enable anchoring. FTIR spectra confirmed this interaction. Infrared imaging revealed distribution of folic acid across the nanoparticle surface. Nanoparticles were obtained in the size range 350-450 nm with RFM loading of 12-14% w/w. Zeta potential confirmed colloidal stability. TEM/SEM revealed spherical morphology. RFMGzFa nanoparticles exhibited sustained release of RFM and folic acid. Folic acid showed sustained release upto 12 h, which was ion exchange mediated. A 480% enhancement in RFM uptake with RFMGzFa nanoparticles compared to 300% with RFMGz nanoparticles in-vitro, in human macrophage cell line U-937, suggested the role of folic acid in folate receptor mediated uptake. Ionic complexation represents a simple non-covalent approach for anchoring folic acid on polymeric nanoparticles of Gantrez.

Assessment of workplace air concentrations of formaldehyde during and before working hours in medical facilities.

PubMed

Higashikubo, Ichiro; Miyauchi, Hiroyuki; Yoshida, Satoru; Tanaka, Shinsuke; Matsuoka, Mitsunori; Arito, Heihachiro; Araki, Akihiro; Shimizu, Hidesuke; Sakurai, Haruhiko

2017-04-07

Workplace air concentrations of formaldehyde (FA) in medical facilities where FA and FA-treated organs were stored and handled were measured before and during working hours and assessed by the official method specified by Work Environment Measurement Law. Sixty-percent of the total facilities examined were judged as inappropriately controlled work environment. The concentrations of FA before working hours by spot sampling were found to exceed 0.1 ppm in some facilities, and tended to increase with increasing volume of containers storing FA and FA-treated materials. Regression analysis revealed that logarithmic concentrations of FA during working hours by the Law-specified analytical method were highly correlated with those before working hours by spot sampling, suggesting the importance for appropriate storing methods of FA and FA-treated materials. The concentrations of FA during working hours are considered to be lowered by effective ventilation of FA-contaminated workplace air and appropriate storage of FA and FA-treated materials in plastic containers in the medical facilities. In particular, such improvement by a local exhaust ventilation system and tightly-sealed containment of FA-treated material were urgently needed for the dissecting room where FA-treated cadavers were prepared and handled for a gross anatomy course in a medical school.

Role of Fatty Acid Kinase in Cellular Lipid Homeostasis and SaeRS-Dependent Virulence Factor Expression in Staphylococcus aureus

PubMed Central

Ericson, Megan E.; Subramanian, Chitra; Frank, Matthew W.

2017-01-01

ABSTRACT The SaeRS two-component system is a master activator of virulence factor transcription in Staphylococcus aureus, but the cellular factors that control its activity are unknown. Fatty acid (FA) kinase is a two-component enzyme system required for extracellular FA uptake and SaeRS activity. Here, we demonstrate the existence of an intracellular nonesterified FA pool in S. aureus that is elevated in strains lacking FA kinase activity. SaeRS-mediated transcription is restored in FA kinase-negative strains when the intracellular FA pool is reduced either by growth with FA-depleted bovine serum albumin to extract the FA into the medium or by the heterologous expression of Neisseria gonorrhoeae acyl-acyl carrier protein synthetase to activate FA for phospholipid synthesis. These data show that FAs act as negative regulators of SaeRS signaling, and FA kinase activates SaeRS-dependent virulence factor production by lowering inhibitory FA levels. Thus, FA kinase plays a role in cellular lipid homeostasis by activating FA for incorporation into phospholipid, and it indirectly regulates SaeRS signaling by maintaining a low intracellular FA pool. PMID:28765222

Hydroxyapatite, fluor-hydroxyapatite and fluorapatite produced via the sol-gel method: bonding to titanium and scanning electron microscopy.

PubMed

Tredwin, Christopher J; Georgiou, George; Kim, Hae-Won; Knowles, Jonathan C

2013-05-01

Hydroxyapatite (HA), fluor-hydroxyapatite (FHA) with varying levels of fluoride ion substitution and fluorapatite (FA) production has been characterised and optimised by the sol-gel method and the dissolution and biological properties of these materials were investigated. It was the objective of this study to investigate the potential bond strength and interaction of these materials with titanium. HA, FHA and FA were synthesised by a sol-gel method. Calcium nitrate and triethyl phosphite were used as precursors under an ethanol-water based solution. Different amounts of ammonium fluoride (NH4F) were incorporated for the preparation of the FHA and FA sol-gels. Using a spin coating technique the sol-gels were coated onto commercially pure titanium disks and crystallised at various temperatures. Using scanning electron microscopy (SEM) and elemental analysis, the surface characteristics, coating thickness and interaction of the Ti substrate and coating were investigated. The bond strengths of the coating to the Ti were investigated using an Instron Universal Load Testing Machine. Statistical analysis was performed with a two-way analysis of variance and post hoc testing with a Bonferroni correction. (1) Coating speed inversely influenced the coating thickness. (2) Increasing fluoride ion substitution and heating temperature significantly increased bond strength and (3) increasing fluoride ion substitution increased the coating thickness. FHA and FA synthesised using the sol-gel technique may offer a superior alternative to coating titanium implants with HA and plasma spraying. HA, FHA and FA materials synthesised by the sol-gel method may also have a use as bone grafting materials. Copyright © 2013 Academy of Dental Materials. Published by Elsevier Ltd. All rights reserved.

Glial activation colocalizes with structural abnormalities in amyotrophic lateral sclerosis.

PubMed

Alshikho, Mohamad J; Zürcher, Nicole R; Loggia, Marco L; Cernasov, Paul; Chonde, Daniel B; Izquierdo Garcia, David; Yasek, Julia E; Akeju, Oluwaseun; Catana, Ciprian; Rosen, Bruce R; Cudkowicz, Merit E; Hooker, Jacob M; Atassi, Nazem

2016-12-13

In this cross-sectional study, we aimed to evaluate brain structural abnormalities in relation to glial activation in the same cohort of participants. Ten individuals with amyotrophic lateral sclerosis (ALS) and 10 matched healthy controls underwent brain imaging using integrated MR/PET and the radioligand [ 11 C]-PBR28. Diagnosis history and clinical assessments including Upper Motor Neuron Burden Scale (UMNB) were obtained from patients with ALS. Diffusion tensor imaging (DTI) analyses including tract-based spatial statistics and tractography were applied. DTI metrics including fractional anisotropy (FA) and diffusivities (mean, axial, and radial) were measured in regions of interest. Cortical thickness was assessed using surface-based analysis. The locations of structural changes, measured by DTI and the areas of cortical thinning, were compared to regional glial activation measured by relative [ 11 C]-PBR28 uptake. In this cohort of individuals with ALS, reduced FA and cortical thinning colocalized with regions demonstrating higher radioligand binding. [ 11 C]-PBR28 binding in the left motor cortex was correlated with FA (r = -0.68, p < 0.05) and cortical thickness (r = -0.75, p < 0.05). UMNB was correlated with glial activation (r = +0.75, p < 0.05), FA (r = -0.77, p < 0.05), and cortical thickness (r = -0.75, p < 0.05) in the motor cortex. Increased uptake of the glial marker [ 11 C]-PBR28 colocalizes with changes in FA and cortical thinning. This suggests a link between disease mechanisms (gliosis and inflammation) and structural changes (cortical thinning and white and gray matter changes). In this multimodal neuroimaging work, we provide an in vivo model to investigate the pathogenesis of ALS. © 2016 American Academy of Neurology.

Glial activation colocalizes with structural abnormalities in amyotrophic lateral sclerosis

PubMed Central

Alshikho, Mohamad J.; Zürcher, Nicole R.; Loggia, Marco L.; Cernasov, Paul; Chonde, Daniel B.; Izquierdo Garcia, David; Yasek, Julia E.; Akeju, Oluwaseun; Catana, Ciprian; Rosen, Bruce R.; Cudkowicz, Merit E.

2016-01-01

Objective: In this cross-sectional study, we aimed to evaluate brain structural abnormalities in relation to glial activation in the same cohort of participants. Methods: Ten individuals with amyotrophic lateral sclerosis (ALS) and 10 matched healthy controls underwent brain imaging using integrated MR/PET and the radioligand [11C]-PBR28. Diagnosis history and clinical assessments including Upper Motor Neuron Burden Scale (UMNB) were obtained from patients with ALS. Diffusion tensor imaging (DTI) analyses including tract-based spatial statistics and tractography were applied. DTI metrics including fractional anisotropy (FA) and diffusivities (mean, axial, and radial) were measured in regions of interest. Cortical thickness was assessed using surface-based analysis. The locations of structural changes, measured by DTI and the areas of cortical thinning, were compared to regional glial activation measured by relative [11C]-PBR28 uptake. Results: In this cohort of individuals with ALS, reduced FA and cortical thinning colocalized with regions demonstrating higher radioligand binding. [11C]-PBR28 binding in the left motor cortex was correlated with FA (r = −0.68, p < 0.05) and cortical thickness (r = −0.75, p < 0.05). UMNB was correlated with glial activation (r = +0.75, p < 0.05), FA (r = −0.77, p < 0.05), and cortical thickness (r = −0.75, p < 0.05) in the motor cortex. Conclusions: Increased uptake of the glial marker [11C]-PBR28 colocalizes with changes in FA and cortical thinning. This suggests a link between disease mechanisms (gliosis and inflammation) and structural changes (cortical thinning and white and gray matter changes). In this multimodal neuroimaging work, we provide an in vivo model to investigate the pathogenesis of ALS. PMID:27837005

Novel Palm Fatty Acid Functionalized Magnetite Nanoparticles for Magnetic Solid-Phase Extraction of Trace Polycyclic Aromatic Hydrocarbons from Environmental Samples.

PubMed

Rozi, Siti Khalijah Mahmad; Nodeh, Hamid Rashidi; Kamboh, Muhammad Afzal; Manan, Ninie Suhana Abdul; Mohamad, Sharifah

2017-07-01

A novel adsorbent, palm fatty acid coated magnetic Fe 3 O 4 nanoparticles (MNP-FA) was successfully synthesized with immobilization of the palm fatty acid onto the surface of MNPs. The successful synthesis of MNP-FA was further confirmed by X-Ray diffraction (XRD), transmission electron microscopy (TEM), Fourier transform infrared spectroscopy (FT-IR) and Energy dispersive X-Ray spectroscopy (EDX) analyses and water contact angle (WCA) measurement. This newly synthesized MNP-FA was applied as magnetic solid phase extraction (MSPE) adsorbent for the enrichment of polycyclic aromatic hydrocarbons (PAHs), namely fluoranthene (FLT), pyrene (Pyr), chrysene (Cry) and benzo(a)pyrene (BaP) from environmental samples prior to High Performance Liquid Chromatography- Diode Array Detector (HPLC-DAD) analysis. The MSPE method was optimized by several parameters such as amount of sorbent, desorption solvent, volume of desorption solvent, extraction time, desorption time, pH and sample volume. Under the optimized conditions, MSPE method provided a low detection limit (LOD) for FLT, Pyr, Cry and BaP in the range of 0.01-0.05 ng mL -1 . The PAHs recoveries of the spiked leachate samples ranged from 98.5% to 113.8% with the RSDs (n = 5) ranging from 3.5% to 12.2%, while for the spiked sludge samples, the recoveries ranged from 81.1% to 119.3% with the RSDs (n = 5) ranging from 3.1% to 13.6%. The recyclability study revealed that MNP-FA has excellent reusability up to five times. Chromatrographic analysis demonstrated the suitability of MNP-FA as MSPE adsorbent for the efficient extraction of PAHs from environmental samples.

Assessing soil quality indicator under different land use and soil erosion using multivariate statistical techniques.

PubMed

Nosrati, Kazem

2013-04-01

Soil degradation associated with soil erosion and land use is a critical problem in Iran and there is little or insufficient scientific information in assessing soil quality indicator. In this study, factor analysis (FA) and discriminant analysis (DA) were used to identify the most sensitive indicators of soil quality for evaluating land use and soil erosion within the Hiv catchment in Iran and subsequently compare soil quality assessment using expert opinion based on soil surface factors (SSF) form of Bureau of Land Management (BLM) method. Therefore, 19 soil physical, chemical, and biochemical properties were measured from 56 different sampling sites covering three land use/soil erosion categories (rangeland/surface erosion, orchard/surface erosion, and rangeland/stream bank erosion). FA identified four factors that explained for 82 % of the variation in soil properties. Three factors showed significant differences among the three land use/soil erosion categories. The results indicated that based upon backward-mode DA, dehydrogenase, silt, and manganese allowed more than 80 % of the samples to be correctly assigned to their land use and erosional status. Canonical scores of discriminant functions were significantly correlated to the six soil surface indices derived of BLM method. Stepwise linear regression revealed that soil surface indices: soil movement, surface litter, pedestalling, and sum of SSF were also positively related to the dehydrogenase and silt. This suggests that dehydrogenase and silt are most sensitive to land use and soil erosion.

Mild and Short-Term Caloric Restriction Prevents Obesity-Induced Cardiomyopathy in Young Zucker Rats without Changing in Metabolites and Fatty Acids Cardiac Profile

PubMed Central

Ruiz-Hurtado, Gema; García-Prieto, Concha F.; Pulido-Olmo, Helena; Velasco-Martín, Juan P.; Villa-Valverde, Palmira; Fernández-Valle, María E.; Boscá, Lisardo; Fernández-Velasco, María; Regadera, Javier; Somoza, Beatriz; Fernández-Alfonso, María S.

2017-01-01

Caloric restriction (CR) ameliorates cardiac dysfunction associated with obesity. However, most of the studies have been performed under severe CR (30–65% caloric intake decrease) for several months or even years in aged animals. Here, we investigated whether mild (20% food intake reduction) and short-term (2-weeks) CR prevented the obese cardiomyopathy phenotype and improved the metabolic profile of young (14 weeks of age) genetically obese Zucker fa/fa rats. Heart weight (HW) and HW/tibia length ratio was significantly lower in fa/fa rats after 2 weeks of CR than in counterparts fed ad libitum. Invasive pressure measurements showed that systolic blood pressure, maximal rate of positive left ventricle (LV) pressure, LV systolic pressure and LV end-diastolic pressure were all significantly higher in obese fa/fa rats than in lean counterparts, which were prevented by CR. Magnetic resonance imaging revealed that the increase in LV end-systolic volume, stroke volume and LV wall thickness observed in fa/fa rats was significantly lower in animals on CR diet. Histological analysis also revealed that CR blocked the significant increase in cardiomyocyte diameter in obese fa/fa rats. High resolution magic angle spinning magnetic resonance spectroscopy analysis of the LV revealed a global decrease in metabolites such as taurine, creatine and phosphocreatine, glutamate, glutamine and glutathione, in obese fa/fa rats, whereas lactate concentration was increased. By contrast, fatty acid concentrations in LV tissue were significantly elevated in obese fa/fa rats. CR failed to restore the LV metabolomic profile of obese fa/fa rats. In conclusion, mild and short-term CR prevented an obesity-induced cardiomyopathy phenotype in young obese fa/fa rats independently of the cardiac metabolic profile. PMID:28203206

Restricted access magnetic materials prepared by dual surface modification for selective extraction of therapeutic drugs from biological fluids

NASA Astrophysics Data System (ADS)

Wang, Yu; Wang, Yuxia; Chen, Lei; Wan, Qian-Hong

2012-02-01

Magnetic porous particles with dual functionality have been prepared by a two-step procedure and evaluated as novel restricted access materials for extraction of therapeutic agents from biological fluids. The magnetic silica particles served as scaffolds were first modified with diol groups, which were then converted to octadecyl esters through reaction with stearoyl chloride. In the second step, the octadecyl esters on the exterior surface were hydrolyzed by the action of lipase to yield magnetic particles with hydrophobic reversed-phase ligands on the inner surface and biocompatible diol groups on the outer surface. The restricted access behavior of the resulting materials was confirmed by differential binding of small molecules such as methotrexate (MTX), leucovorin (LV) and folic acid (FA) relative to bovine serum albumin. While MTX, LV and FA were all bound to the magnetic particles with high affinity, the adsorption of the protein was markedly reduced due to size exclusion effect. The utility of the magnetic particles for sample preparation was tested in solid-phase extraction of MTX, LV and FA from spiked human serum and the effects of the SPE conditions on the recovery of the analytes were systematically studied. Moreover, the magnetic particle-based sample preparation procedure coupled with reversed-phase liquid chromatography analysis was validated in terms of specificity, linearity and reproducibility. The method was shown to be free from interference of endogenous compounds and linear over the concentration range of 0.5-10 μg/mL for the three drugs studied. The limits of detection for the three drugs in serum were in the range of 0.160-0.302 μg/mL. Reproducibility expressed as the RSD of the recovery for ten replicated extractions at three different concentrations was found to be less than 8.93%. With a unique combination of surface functionality with magnetic cores, the restricted access magnetic particles may be adapted in automated and high throughput protocols for routine analysis of a large volume of clinical samples.

Fabrication and characterization of aluminium hybrid composites reinforced with fly ash and silicon carbide through powder metallurgy

NASA Astrophysics Data System (ADS)

Bilal Naim Shaikh, Mohd; Arif, Sajjad; Arif Siddiqui, M.

2018-04-01

This paper reports the fabrication and characterization of aluminium hybrid composites (AMCs) reinforced with commonly available and inexpensive fly ash (FA, 0, 5, 10 and 15 wt.%) particles along silicon carbide (SiC) using powder metallurgy process. Scanning electron microscopy (SEM) and x-ray diffraction (XRD) were employed for microstructural characterization and phase identification respectively. Wear behaviour were investigated using pin-on-disc wear tester for the different combinations of wear parameters like load (10, 20 and 30 N), sliding speed (1.5, 2 and 2.5 m s‑1) and sliding distance (300, 600 and 900 m). SEM confirms the uniform distribution of FA and SiC in aluminium matrix. The hardness of Al/SiC/FA is increased by 20%–25% while wear rate decreased by 15%–40%. From wear analysis, sliding distance was the least significant parameter influencing the wear loss followed by applied load and sliding speed. To identify the mechanism of wear, worn out surface were also analysed by SEM.

Principal Components of Thermography analyses of the Silk Tomb, Petra (Jordan)

NASA Astrophysics Data System (ADS)

Gomez-Heras, Miguel; Alvarez de Buergo, Monica; Fort, Rafael

2015-04-01

This communication presents the results of an active thermography survey of the Silk Tomb, which belongs to the Royal Tombs compound in the archaeological city of Petra in Jordan. The Silk Tomb is carved in the variegated Palaeozoic Umm Ishrin sandstone and it is heavily backweathered due to surface runoff from the top of the cliff where it is carved. Moreover, the name "Silk Tomb" was given because of the colourful display of the variegated sandstone due to backweathering. A series of infrared images were taken as the façade was heated by sunlight to perform a Principal Component of Thermography analyses with IR view 1.7.5 software. This was related to indirect moisture measurements (percentage of Wood Moisture Equivalent) taken across the façade, by means of a Protimeter portable moisture meter. Results show how moisture retention is deeply controlled by lithological differences across the façade. Research funded by Geomateriales 2 S2013/MIT-2914 and CEI Moncloa (UPM, UCM, CSIC) through a PICATA contract and the equipment from RedLAbPAt Network

Structural brain and neuropsychometric changes associated with pediatric bipolar disorder with psychosis.

PubMed

James, Anthony; Hough, Morgan; James, Susan; Burge, Linda; Winmill, Louise; Nijhawan, Sunita; Matthews, Paul M; Zarei, Mojtaba

2011-02-01

To identify neuropsychological and structural brain changes using a combination of high-resolution structural and diffusion tensor imaging in pediatric bipolar disorder (PBD) with psychosis (presence of delusions and or hallucinations). We recruited 15 patients and 20 euthymic age- and gender-matched healthy controls. All subjects underwent high-resolution structural and diffusion tensor imaging. Voxel-based morphometry (VBM), tract-based spatial statistics (TBSS), and probabilistic tractography were used to analyse magnetic resonance imaging data. The PBD subjects had normal overall intelligence with specific impairments in working memory, executive function, language function, and verbal memory. Reduced gray matter (GM) density was found in the left orbitofrontal cortex, left pars triangularis, right premotor cortex, occipital cortex, right occipital fusiform gyrus, and right crus of the cerebellum. TBSS analysis showed reduced fractional anisotropy (FA) in the anterior corpus callosum. Probabilistic tractography from this cluster showed that this region of the corpus callosum is connected with the prefrontal cortices, including those regions whose density is decreased in PBD. In addition, FA change was correlated with verbal memory and working memory, while more widespread reductions in GM density correlated with working memory, executive function, language function, and verbal memory. The findings suggest widespread cortical changes as well as specific involvement of interhemispheric prefrontal tracts in PBD, which may reflect delayed myelination in these tracts. © 2011 John Wiley and Sons A/S.

A positive relationship between harm avoidance and brain nicotinic acetylcholine receptor availability.

PubMed

Storage, Steven; Mandelkern, Mark A; Phuong, Jonathan; Kozman, Maggie; Neary, Meaghan K; Brody, Arthur L

2013-12-30

Prior research indicates that disturbance of cholinergic neurotransmission reduces anxiety, leading to the hypothesis that people with heightened cholinergic function have a greater tendency toward anxiety-like and/or harm-avoidant behavior. We sought to determine if people with elevated levels of harm avoidance (HA), a dimension of temperament from the Temperament and Character Inventory (TCI), have high α4β2* nicotinic acetylcholine receptor (nAChR) availability. Healthy adults (n=105; 47 non-smokers and 58 smokers) underwent bolus-plus-continuous infusion positron emission tomography (PET) scanning using the radiotracer 2-[18F]fluoro-3-(2(S)azetidinylmethoxy) pyridine (abbreviated as 2-FA). During the uptake period of 2-FA, participants completed the TCI. The central study analysis revealed a significant association between total HA and mean nAChR availability, with higher total HA scores being linked with greater nAChR availability. In examining HA subscales, both 'Fear of Uncertainty' and 'Fatigability' were significant, based on higher levels of these characteristics being associated with greater nAChR availabilities. This study adds to a growing body of knowledge concerning the biological basis of personality and may prove useful in understanding the pathophysiology of psychiatric disorders (such as anxiety disorders) that have similar characteristics to HA. Study findings may indicate that heightened cholinergic neurotransmission is associated with increased anxiety-like traits. Published by Elsevier Ireland Ltd.

A positive relationship between harm avoidance and brain nicotinic acetylcholine receptor availability

PubMed Central

Storage, Steven; Mandelkern, Mark A.; Phuong, Jonathan; Kozman, Maggie; Neary, Meaghan K.; Brody, Arthur L.

2013-01-01

Prior research indicates that disturbance of cholinergic neurotransmission reduces anxiety, leading to the hypothesis that people with heightened cholinergic function have a greater tendency toward anxiety-like and/or harm-avoidant behavior. We sought to determine if people with elevated levels of harm avoidance (HA), a dimension of temperament from the Temperament and Character Inventory (TCI), have high α4β2* nicotinic acetylcholine receptor (nAChR) availability. Healthy adults (n = 105; 47 non-smokers and 58 smokers) underwent bolus-plus-continuous infusion positron emission tomography (PET) scanning using the radiotracer 2-[18F]fluoro-3-(2(S)azetidinylmethoxy) pyridine (abbreviated as 2-FA). During the uptake period of 2-FA, participants completed the TCI. The central study analysis revealed a significant association between total HA and mean nAChR availability, with higher total HA scores being linked with greater nAChR availability. In examining HA subscales, both ‘Fear of Uncertainty’ and ‘Fatigability’ were significant, based on higher levels of these characteristics being associated with greater nAChR availabilities. This study adds to a growing body of knowledge concerning the biological basis of personality and may prove useful in understanding the pathophysiology of psychiatric disorders (such as anxiety disorders) that have similar characteristics to HA. Study findings may indicate that heightened cholinergic neurotransmission is associated with increased anxiety-like traits. PMID:24148908

Reduced fiber integrity and cognitive control in adolescents with internet gaming disorder.

PubMed

Xing, Lihong; Yuan, Kai; Bi, Yanzhi; Yin, Junsen; Cai, Chenxi; Feng, Dan; Li, Yangding; Song, Min; Wang, Hongmei; Yu, Dahua; Xue, Ting; Jin, Chenwang; Qin, Wei; Tian, Jie

2014-10-24

The association between the impaired cognitive control and brain regional abnormalities in Internet gaming disorder (IGD) adolescents had been validated in numerous studies. However, few studies focused on the role of the salience network (SN), which regulates dynamic communication among brain core neurocognitive networks to modulate cognitive control. Seventeen IGD adolescents and 17 healthy controls participated in the study. By combining resting-state functional connectivity and diffusion tensor imaging (DTI) tractography methods, we examined the changes of functional and structural connections within SN in IGD adolescents. The color-word Stroop task was employed to assess the impaired cognitive control in IGD adolescents. Correlation analysis was carried out to investigate the relationship between the neuroimaging indices and behavior performance in IGD adolescents. The impaired cognitive control in IGD was validated by more errors during the incongruent condition in color-word Stroop task. The right SN tract showed the decreased fractional anisotropy (FA) in IGD adolescents, though no significant differences of functional connectivity were detected. Moreover, the FA values of the right SN tract were negatively correlated with the errors during the incongruent condition in IGD adolescents. Our results revealed the disturbed structural connectivity within SN in IGD adolescents, which may be related with impaired cognitive control. It is hoped that the brain-behavior relationship from network perspective may enhance the understanding of IGD. Copyright © 2014 Elsevier B.V. All rights reserved.

Effects of Uric Acid on the Alterations of White Matter Connectivity in Patients with Major Depression.

PubMed

Sohn, Hoyoung; Kwon, Min-Soo; Lee, Sun-Woo; Oh, Jongsoo; Kim, Min-Kyoung; Lee, Sang-Hyuk; Lee, Kang Soo; Kim, Borah

2018-06-07

Uric acid is a non-enzymatic antioxidant associated with depression. Despite its known protective role in other brain disorders, little is known about its influence on the structural characteristics of brains of patients with major depressive disorder (MDD). This study explored the association between uric acid and characteristics of white matter (WM) in patients with MDD. A total of 32 patients with MDD and 23 healthy controls (HCs) were examined. All participants were scored based on the Beck Depression Inventory and Beck Anxiety Inventory at baseline. All patients were also rated with the Hamilton Depression Rating Scale. We collected blood samples from all participants immediately after their enrollment and before the initiation of antidepressants in case of patients. Tract-based spatial statistics were used for all imaging analyses. Lower fractional anisotropy (FA) and higher radial diffusivity (RD) values were found in the MDD group than in the HC group. Voxelwise correlation analysis revealed that the serum uric acid levels positively correlated with the FA and negatively with the RD in WM regions that previously showed significant group differences in the MDD group. The correlated areas were located in the left anterior corona radiata, left frontal lobe WM, and left anterior cingulate cortex WM. The present study suggests a significant association between altered WM connectivity and serum uric acid levels in patients with MDD, possibly through demyelination.

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

PubMed Central

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

2013-01-01

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