Modulation of the virus-receptor interaction by mutations in the V5 loop of feline immunodeficiency virus (FIV) following in vivo escape from neutralising antibody

<b>BACKGROUND:</b> In the acute phase of infection with feline immunodeficiency virus (FIV), the virus targets activated CD4+ T cells by utilising CD134 (OX40) as a primary attachment receptor and CXCR4 as a co-receptor. The nature of the virus-receptor interaction varies between isolates; strains such as GL8 and CPGammer recognise a "complex" determinant on CD134 formed by cysteine-rich domains (CRDs) 1 and 2 of the molecule while strains such as PPR and B2542 require a more "simple" determinant comprising CRD1 only for infection. These differences in receptor recognition manifest as variations in sensitivity to receptor antagonists. In this study, we ask whether the nature of the virus-receptor interaction evolves in vivo.<p></p> <b>RESULTS:</b> Following infection with a homogeneous viral population derived from a pathogenic molecular clone, a quasispecies emerged comprising variants with distinct sensitivities to neutralising antibody and displaying evidence of conversion from a "complex" to a "simple" interaction with CD134. Escape from neutralising antibody was mediated primarily by length and sequence polymorphisms in the V5 region of Env, and these alterations in V5 modulated the virus-receptor interaction as indicated by altered sensitivities to antagonism by both anti-CD134 antibody and soluble CD134.<p></p> <b>CONCLUSIONS:</b> The FIV-receptor interaction evolves under the selective pressure of the host humoral immune response, and the V5 loop contributes to the virus-receptor interaction. Our data are consistent with a model whereby viruses with distinct biological properties are present in early versus late infection and with a shift from a "complex" to a "simple" interaction with CD134 with time post-infection.<p></p&gt

Differences in selectivity to natural images in early visual areas (V1–V3)

High-level regions of the ventral visual pathway respond more to intact objects compared to scrambled objects. The aim of this study was to determine if this selectivity for objects emerges at an earlier stage of processing. Visual areas (V1–V3) were defined for each participant using retinotopic mapping. Participants then viewed intact and scrambled images from different object categories (bottle, chair, face, house, shoe) while neural responses were measured using fMRI. Our rationale for using scrambled images is that they contain the same low-level properties as the intact objects, but lack the higher-order combinations of features that are characteristic of natural images. Neural responses were higher for scrambled than intact images in all regions. However, the difference between intact and scrambled images was smaller in V3 compared to V1 and V2. Next, we measured the spatial patterns of response to intact and scrambled images from different object categories. We found higher within-category compared to between category correlations for both intact and scrambled images demonstrating distinct patterns of response. Spatial patterns of response were more distinct for intact compared to scrambled images in V3, but not in V1 or V2. These findings demonstrate the emergence of selectivity to natural images in V3

The N-Terminal residues 43 to 60 form the interface for dopamine mediated α-synuclein dimerisation

α-synuclein (α-syn) is a major component of the intracellular inclusions called Lewy bodies, which are a key pathological feature in the brains of Parkinson's disease patients. The neurotransmitter dopamine (DA) inhibits the fibrillisation of α-syn into amyloid, and promotes α-syn aggregation into SDS-stable soluble oligomers. While this inhibition of amyloid formation requires the oxidation of both DA and the methionines in α-syn, the molecular basis for these processes is still unclear. This study sought to define the protein sequences required for the generation of oligomers. We tested N- (α-syn residues 43-140) and C-terminally (1-95) truncated α-syn, and found that similar to full-length protein both truncated species formed soluble DA: α-syn oligomers, albeit 1-95 had a different profile. Using nuclear magnetic resonance (NMR), and the N-terminally truncated α-syn 43-140 protein, we analysed the structural characteristics of the DA:α-syn 43-140 dimer and α-syn 43-140 monomer and found the dimerisation interface encompassed residues 43 to 60. Narrowing the interface to this small region will help define the mechanism by which DA mediates the formation of SDS-stable soluble DA:α-syn oligomers

The disruption of proteostasis in neurodegenerative diseases

Cells count on surveillance systems to monitor and protect the cellular proteome which, besides being highly heterogeneous, is constantly being challenged by intrinsic and environmental factors. In this context, the proteostasis network (PN) is essential to achieve a stable and functional proteome. Disruption of the PN is associated with aging and can lead to and/or potentiate the occurrence of many neurodegenerative diseases (ND). This not only emphasizes the importance of the PN in health span and aging but also how its modulation can be a potential target for intervention and treatment of human diseases.info:eu-repo/semantics/publishedVersio

Laparoscopy in management of appendicitis in high-, middle-, and low-income countries: a multicenter, prospective, cohort study.

BACKGROUND: Appendicitis is the most common abdominal surgical emergency worldwide. Differences between high- and low-income settings in the availability of laparoscopic appendectomy, alternative management choices, and outcomes are poorly described. The aim was to identify variation in surgical management and outcomes of appendicitis within low-, middle-, and high-Human Development Index (HDI) countries worldwide. METHODS: This is a multicenter, international prospective cohort study. Consecutive sampling of patients undergoing emergency appendectomy over 6 months was conducted. Follow-up lasted 30 days. RESULTS: 4546 patients from 52 countries underwent appendectomy (2499 high-, 1540 middle-, and 507 low-HDI groups). Surgical site infection (SSI) rates were higher in low-HDI (OR 2.57, 95% CI 1.33-4.99, p = 0.005) but not middle-HDI countries (OR 1.38, 95% CI 0.76-2.52, p = 0.291), compared with high-HDI countries after adjustment. A laparoscopic approach was common in high-HDI countries (1693/2499, 67.7%), but infrequent in low-HDI (41/507, 8.1%) and middle-HDI (132/1540, 8.6%) groups. After accounting for case-mix, laparoscopy was still associated with fewer overall complications (OR 0.55, 95% CI 0.42-0.71, p < 0.001) and SSIs (OR 0.22, 95% CI 0.14-0.33, p < 0.001). In propensity-score matched groups within low-/middle-HDI countries, laparoscopy was still associated with fewer overall complications (OR 0.23 95% CI 0.11-0.44) and SSI (OR 0.21 95% CI 0.09-0.45). CONCLUSION: A laparoscopic approach is associated with better outcomes and availability appears to differ by country HDI. Despite the profound clinical, operational, and financial barriers to its widespread introduction, laparoscopy could significantly improve outcomes for patients in low-resource environments. TRIAL REGISTRATION: NCT02179112

Bioconjugates of Glucose Oxidase and Gold Nanorods Based on Electrostatic Interaction with Enhanced Thermostability

Bioconjugates made up of an enzyme and gold nanorods (GNRs) were fabricated by electrostatic interactions (layer-by-layer method, LBL) between anionic glucose oxidase (GOD) and positively charged GNRs. The assembled processes were monitored by UV–Vis spectra, zeta potential measurements, and transmission electron microscopy. The enzyme activity assays of the obtained bioconjugates display a relatively enhanced thermostability behavior in contrast with that of free enzyme. Free GOD in solution only retains about 22% of its relative activity at 90 °C. Unexpectedly, the immobilized GOD on GNRs still retains about 39.3% activity after the same treatment. This work will be of significance for the biologic enhancement using other kinds of anisotropic nanostructure and suggests a new way of enhancing enzyme thermostability using anisotropic metal nanomaterials

The Effect of Bacterial Infection on the Biomechanical Properties of Biological Mesh in a Rat Model

BACKGROUND: The use of biologic mesh to repair abdominal wall defects in contaminated surgical fields is becoming the standard of practice. However, failure rates and infections of these materials persist clinically. The purpose of this study was to determine the mechanical properties of biologic mesh in response to a bacterial encounter. METHODS: A rat model of Staphylococcus aureus colonization and infection of subcutaneously implanted biologic mesh was used. Samples of biologic meshes (acellular human dermis (ADM) and porcine small intestine submucosa (SIS)) were inoculated with various concentrations of methicillin-resistant Staphylococcus aureus [10(5), 10(9) colony-forming units] or saline (control) prior to wound closure (n = 6 per group). After 10 or 20 days, meshes were explanted, and cultured for bacteria. Histological changes and bacterial recovery together with biomechanical properties were assessed. Data were compared using a 1-way ANOVA or a Mann-Whitney test, with p<0.05. RESULTS: The overall rate of staphylococcal mesh colonization was 81% and was comparable in the ADM and SIS groups. Initially (day 0) both biologic meshes had similar biomechanical properties. However after implantation, the SIS control material was significantly weaker than ADM at 20 days (p = 0.03), but their corresponding modulus of elasticity were similar at this time point (p>0.05). After inoculation with MRSA, a time, dose and material dependent decrease in the ultimate tensile strength and modulus of elasticity of SIS and ADM were noted compared to control values. CONCLUSION: The biomechanical properties of biologic mesh significantly decline after colonization with MRSA. Surgeons selecting a repair material should be aware of its biomechanical fate relative to other biologic materials when placed in a contaminated environment

Measures in Visualization Space

Postponed access: the file will be available after 2021-08-12Measurement is an integral part of modern science, providing the fundamental means for evaluation, comparison, and prediction. In the context of visualization, several different types of measures have been proposed, ranging from approaches that evaluate particular aspects of visualization techniques, their perceptual characteristics, and even economic factors. Furthermore, there are approaches that attempt to provide means for measuring general properties of the visualization process as a whole. Measures can be quantitative or qualitative, and one of the primary goals is to provide objective means for reasoning about visualizations and their effectiveness. As such, they play a central role in the development of scientific theories for visualization. In this chapter, we provide an overview of the current state of the art, survey and classify different types of visualization measures, characterize their strengths and drawbacks, and provide an outline of open challenges for future research.acceptedVersio

Does General Parenting Context Modify Adolescents' Appraisals and Coping with a Situation of Parental Regulation? The Case of Autonomy-Supportive Parenting

Theory and research suggest that adolescents differ in their appraisals and coping reactions in response to parental regulation. Less is known, however, about factors that determine these differences in adolescents’ responses. In this study, we examined whether adolescents' appraisals and coping reactions depend upon parents’ situation-specific autonomy-supportive or controlling communication style (i.e., the situation) in interaction with adolescents’ past experiences with general autonomy-supportive parenting (i.e., the parenting context). Whereas in Study 1 (N = 176) adolescents’ perceived general autonomy-supportive parenting context was assessed at one point in time, in Study 2 (N = 126) it was assessed multiple times across a 6-year period, allowing for an estimation of trajectories of perceived autonomy-supportive parenting context. In each study, adolescents read a vignette-based scenario depicting a situation of maternal regulation (i.e., a request to study more), which was communicated in either an autonomy-supportive or a controlling way. Following this scenario, they reported upon their appraisals and their anticipated coping reactions. Results of each study indicated that both the autonomy-supportive (relative to the controlling) situation and the perceived autonomy-supportive parenting context generally related to more positive appraisals (i.e., more autonomy need satisfaction, less autonomy need frustration), as well as to more constructive coping responses (i.e., less oppositional defiance and submission, more negotiation and accommodation). In addition, situation × context interactions were found, whereby adolescents growing up in a more autonomy-supportive context seemed to derive greater benefits from the exposure to an autonomy-supportive situation and reacted more constructively to a controlling situation

Activation of the AMP-Activated Protein Kinase by Eicosapentaenoic Acid (EPA, 20:5 n-3) Improves Endothelial Function In Vivo

The aim of the present study was to test the hypothesis that the cardiovascular-protective effects of eicosapentaenoic acid (EPA) may be due, in part, to its ability to stimulate the AMP-activated protein kinase (AMPK)-induced endothelial nitric oxide synthase (eNOS) activation. The role of AMPK in EPA-induced eNOS phosphorylation was investigated in bovine aortic endothelial cells (BAEC), in mice deficient of either AMPKα1 or AMPKα2, in eNOS knockout (KO) mice, or in Apo-E/AMPKα1 dual KO mice. EPA-treatment of BAEC increased both AMPK-Thr172 phosphorylation and AMPK activity, which was accompanied by increased eNOS phosphorylation, NO release, and upregulation of mitochondrial uncoupling protein-2 (UCP-2). Pharmacologic or genetic inhibition of AMPK abolished EPA-enhanced NO release and eNOS phosphorylation in HUVEC. This effect of EPA was absent in the aortas isolated from either eNOS KO mice or AMPKα1 KO mice fed a high-fat, high-cholesterol (HFHC) diet. EPA via upregulation of UCP-2 activates AMPKα1 resulting in increased eNOS phosphorylation and consequent improvement of endothelial function in vivo