4 research outputs found

    Vulnerability to stress: personality facet of vulnerability is associated with cardiovascular adaptation to recurring stress

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    It is increasingly suggested that personality traits are critical to understanding patterns of cardiovascular stress adaptation. However, studies have focused on higher-order traits with no research having examined underlying facet effects to repeated stress. The examination of facets provides a more granular examination, which has the potential to identify specific personality components that are relevant within the context of psychophysiological stress adaptation. This study objective was to determine if the underlying facets which encapsulate the dimension of emotional stability, are associated with cardiovascular adaptation to recurring stress. Continuous cardiovascular monitoring and psychometric measures were collated from 79 healthy young male and female adults, across a protocol of recurring active stress tasks. Multiple regression analysis revealed that the facet of vulnerability was associated with systolic and diastolic blood pressure adaptation across the protocol. More specifically, vulnerability was negatively associated with adaptation to recurring stress, such that those highest in vulnerability displayed a sensitization to the recurring stressor. No significant effects emerged for any other facet. Importantly, this research adds to the existing literature examining stress adaptation and has implications for future research on the relevance of examining facet effects. This study is the first to implicate the personality facet of vulnerability which encapsulates an individual's tendency to feel unable to cope with stress and becoming hopeless when faced with emergency situations, in the context of cardiovascular stress adaptation. Taken together, this study suggests that the facet of vulnerability is a critical component to consider in the context of cardiovascular stress adaptation

    An integrative network analysis framework for identifying molecular functions in complex disorders examining major depressive disorder as a test case

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    In addition to the psychological depressive phenotype, major depressive disorder (MDD) patients are also associated with underlying immune dysregulation that correlates with metabolic syndrome prevalent in depressive patients. A robust integrative analysis of biological pathways underlying the dysregulated neural connectivity and systemic inflammatory response will provide implications in the development of effective strategies for the diagnosis, management and the alleviation of associated comorbidities. In the current study, focusing on MDD, we explored an integrative network analysis methodology to analyze transcriptomic data combined with the meta-analysis of biomarker data available throughout public databases and published scientific peer-reviewed articles. Detailed gene set enrichment analysis and complex protein–protein, gene regulatory and biochemical pathway analysis has been undertaken to identify the functional significance and potential biomarker utility of differentially regulated genes, proteins and metabolite markers. This integrative analysis method provides insights into the molecular mechanisms along with key glycosylation dysregulation underlying altered neutrophil-platelet activation and dysregulated neuronal survival maintenance and synaptic functioning. Highlighting the significant gap that exists in the current literature, the network analysis framework proposed reduces the impact of data gaps and permits the identification of key molecular signatures underlying complex disorders with multiple etiologies such as within MDD and presents multiple treatment options to address their molecular dysfunctio

    Effect of Nanoparticle Stabilization and Physicochemical Properties on Exposure Outcome: Acute Toxicity of Silver Nanoparticle Preparations in Zebrafish (<i>Danio rerio</i>)

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    Nanotechnology has vast potential for expanded development and novel application in numerous sectors of society. With growing use and applications, substantial production volumes and associated environmental release can be anticipated. Exposure effect of nanoparticles (NP) on biological systems may be intrinsic to their physicochemical properties introducing unknown associated risk. Herein, we expand the knowledge of health and environmental impact of silver nanoparticles (AgNPs), testing the acute toxicity of 14 AgNP preparations on developing zebrafish embryos (<i>Danio rerio</i>). Toxicological end points, including mortality, hatching rate, and heart rate were recorded. Concentration, stabilization agent and physicochemical properties were monitored as contributing outcome factors. Our findings indicate wide ranging LC<sub>50</sub> 24 h postfertilization values (0.487 ppm (0.315, 0.744 95% CI) to 47.89 ppm (18.45, 203.49 95% CI)), and indicate surface charge and ionic dissolution as key contributory factors in AgNP exposure outcome

    Development of a Convenient Competitive ELISA for the Detection of the Free and Protein-Bound Nonhuman Galactosyl-α-(1,3)-Galactose Epitope Based on Highly Specific Chicken Single-Chain Antibody Variable-Region Fragments

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    The presence of the nonhuman galactosyl-α-(1,3)-galactose (Gal-α-(1,3)-Gal) carbohydrate epitope on a number of recombinant therapeutic proteins has recently been reported, renewing interest in this immunogenic carbohydrate epitope. It is well-known that this motif is the primary contributing factor in hyperacute rejection of porcine organ xenograft, due to the existence of natural antibodies against this epitope in human serum. Though the number of epitopes on recombinant glycoproteins may be low when compared directly to whole tissue, circulating anti-Gal-α-R immunoglobulins can still induce anaphylaxis. Therefore, there is a need for rapid and convenient methods for detection and monitoring of this epitope in biopharmaceuticals produced in recombinant mammalian systems. To this end, we have generated immune-challenged chicken single-chain antibody variable-region fragment (scFv) libraries targeting the Gal-α-(1,3)-Gal motif and have selected a panel of scFv's that bind the target. We have used one of these antibodies to develop a competitive ELISA for both free and protein-bound Gal-α-(1,3)-Gal and have demonstrated that the ELISA is specific for the target and can be used to determine the loading of the target on glycoproteins. This competitive ELISA will provide a convenient method of detecting and quantifying Gal-α-(1,3)-Gal on therapeutic glycoproteins
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