Localization of a collagen-interactive domain of human von Willebrand factor between amino acid residues Gly 911 and Glu 1,365

A collagen-binding domain of von Willebrand factor (vWF) has been identified in the central part of the molecule by comparing the binding properties of vWF and Staphylococcus aureus V-8 protease-generated vWF fragments with collagen. The binding of purified human vWF to human type III collagen was found to be specific. At saturation, 38 to 50.2 micrograms of vWF bound per milligram of collagen. Scatchard plots derived from binding isotherms demonstrated the presence of at least two classes of binding sites. Purified vWF was digested with S aureus V-8 protease into two complementary fragments (SpIII and SpII). SpII, the C-terminal end of vWF (amino acid residues 1,366 to 2,050), was totally devoid of affinity for collagen. Contrarily, purified SpIII, the N-terminal part of vWF (residues 1 to 1,365), totally displaced vWF binding and specifically bound to collagen. At saturation, 25 to 45 micrograms of SpIII bound per milligram of collagen. Scatchard plots demonstrated the presence of a single class of binding sites. SpIII was further digested with the same enzyme to generate SpI, a 52-kilodalton fragment from the C-terminal part of SpIII (residues 911 to 1,365). Spl induced a dose-dependent inhibition of both vWF and SpIII binding to collagen. A series of six monoclonal antibodies against SpIII that completely abolished vWF and SpIII interaction with collagen also bound to SpI. In conclusion, SpI extending between amino acid residues 911 and 1,365 of vWF contains a specific site that interacts with human type III collagen.     

Low CD4 T cell counts before HIV-1 seroconversion do not affect disease progression in Ethiopian factory workers

BACKGROUND: Human immunodeficiency virus type 1 (HIV-1)-uninfected Ethiopians have lower CD4 T cell counts than do other populations in Africa and industrialized countries. We studied whether this unique immunological profile results in shorter survival times in HIV-1-infected Ethiopians. METHODS: Data from an open cohort study of 149 HIV-1-infected factory workers in Ethiopia for 1997-2002 were used. To estimate survival times, a continuous-time Markov model was designed on the basis of CD4 T cell counts and World Health Organization clinical staging. By use of a random-effects model, decline in CD4 T cell counts was compared between HIV-1-infected Ethiopian and Dutch individuals. RESULTS: Median survival times were in the range of 9.1-13.7 years, depending on the approach used. This range is similar to that for populations in industrialized countries before the advent of antiretroviral therapy. Ethiopians had a lower annual decline in CD4 T cell counts than did Dutch individuals, which remained when groups with similar CD4 T cell count categories were compared. Moreover, the slower decline in CD4 T cell counts was not due merely to lower HIV-1 RNA loads or an absence of syncytium-inducing/X4 HIV-1 subtype C strains in Ethiopians. CONCLUSIONS: Low baseline CD4 T cell counts do not imply shorter survival times in Ethiopians than in other populations, presumably because of a slower decline in CD4 T cell counts.     

Oxygen reduction reaction on Pt-skin Pt3V(111) fuel cell cathode: a density functional theory study

Pt-non-precious transition metals (Pt-NPTMs) alloy electrocatalysts have gained considerable attention to develop cheaper and efficient electrocatalysts for oxygen reduction reaction (ORR) in proton exchange membrane fuel cells (PEMFCs). In this report, density functional theory (DFT) has been applied to study the catalytic activity of Pt-skin Pt₃V(111) electrocatalyst for ORR in PEMFCs. The results revealed that the ORR intermediates (O, OH and OOH) have lower binding energies on Pt-skin Pt₃V(111) compared to pure Pt(111) surface. The ORR on Pt-skin Pt₃V(111) surface proceed via OOH dissociation with an activation energy of 0.33 eV. The formation of OH is found to be the rate determining step with an activation energy of 0.64 eV, which is even lower than in pure Pt(111) surface (0.72 eV). This indicates a better performance of Pt-skin Pt₃V(111) for ORR compared to pure Pt(111) surface. Moreover, the DFT results revealed that the negative formation energy of the Pt₃V alloy and the positive dissolution potential shift of the surface Pt atoms revealed the better stability of Pt-skin Pt₃V(111) surface over pristine Pt(111) surface. Due to the improved activity and better stability, the new Pt₃V alloy electrocatalyst is very promising for the development of low-cost and efficient PEMFCs.

Pt-non-precious transition metals (Pt-NPTMs) alloy electrocatalysts have gained considerable attention to develop cheaper and efficient electrocatalysts for oxygen reduction reaction (ORR) in proton exchange membrane fuel cells (PEMFCs).     

The prevalence of pulmonary tuberculosis among miners from the Karonga,Rumphi, Kasungu and Lilongwe Districts of Malawi in 2019

IntroductionMiners in sub-Saharan Africa have a greater risk of tuberculosis (TB) than any other working population in the world. In spite of the presence of large and vulnerable population of miners in Malawi, no previous study has aimed to assess the burden of TB among these miners. This study aimed to determine the prevalence of pulmonary tuberculosis (PTB) and health-seeking behaviour (HSB) in a population of miners in Malawi, and a range of associated factors. Our goal was to develop a method to identify missing cases of TB.MethodsWe conducted a cross-sectional study in the Karonga, Rumphi, Kasungu and Lilongwe districts of Malawi in 2019. We calculated frequencies, proportions, odds ratios (ORs) and their 95% confidence intervals (95% CIs), and used the chi-square test in STATA version15.1 to investigate the burden and magnitude of PTB in the mining sector. Bivariate and multivariate logistic regression models were also fitted for PTB and HSB.ResultsOf the 2400 miners approached, we were able to interview 2013 (84%). Of these, 1435 (71%) were males, 1438 (71%) had known HIV status and 272 (14%) had PTB. Multivariate analysis showed that the miners performing informal mining were 50% more likely to develop PTB compared with those in formal mining (adjusted odds ratio [AOR]=1.50, 95% CI: 1.10–2.05, P=0.01). A total of 459 (23% of 2013) miners had presumptive TB. Of these, 120 (26%) sought health care; 80% sought health care at health facilities. Multivariate analysis also showed that miners who experienced night sweats were less likely to seek health care compared with those without night sweats (AOR=0.52, 95% CI: 0.30–0.90, P=0.02).ConclusionThe prevalence of PTB was higher among miners than in the general population. Consequently, targeted TB screening programmes for miners may represent a suitable strategy to adopt if we are to end TB by 2030. Poor health-seeking behaviours among miners is worrisome and further qualitative research is necessary to understand the barriers to accessing health care in these settings.     

Mediators of socioeconomic inequalities in dietary behaviours among youth: A systematic review

Children and adolescents with a lower socioeconomic position have poorer dietary behaviours compared to their counterparts with a higher socioeconomic position. A better understanding of the mechanisms behind such socioeconomic inequalities is vital to identify targets for interventions aimed at tackling these inequalities. This systematic review aimed to summarize existing evidence regarding the mediators of socioeconomic differences in dietary behaviours among youth. A systematic literature search of MEDLINE, Embase, PsycINFO, and Web of Science databases yielded 20 eligible studies. The dietary behaviours included in the reviewed studies were the intake of fruit and vegetables, sugar‐sweetened beverages, unhealthy snacks/fast food and breakfast. The consistent mediators of the effects of socioeconomic position on dietary behaviours among youth were: self‐efficacy, food preferences and knowledge at the intrapersonal level; and availability and accessibility of food items at home, food rules and parental modelling at the interpersonal level. Few studies including mediators at the organisational, community or policy levels were found. Our review found several modifiable factors at the intrapersonal and interpersonal levels that could be targeted in interventions aimed at combating inequalities in dietary behaviours among youth. Rigorous studies exploring organisational, community and policy level mediators are warranted.     

Boron and pyridinic nitrogen-doped graphene as potential catalysts for rechargeable non-aqueous sodium–air batteries

In this work, we performed density functional theory (DFT) analysis of nitrogen (N)- and boron (B)-doped graphene, and N,B-co-doped graphene as potential catalysts for rechargeable non-aqueous sodium–air batteries. Four steps of an NaO₂ growth and depletion mechanism model were implemented to study the effects of B- and N-doped and co-doped graphene on the reaction pathways, overpotentials, and equilibrium potentials. The DFT results revealed that two-boron- and three-nitrogen (pyridinic)-doped graphene exhibited plausible reaction pathways at the lowest overpotentials, especially during the charging process (approximately 200 mV), thus, significantly improving the oxygen reduction and oxidation reactions of pristine graphene. In addition, pyridinic nitrogen-doped graphene meaningfully increased the equilibrium potential by approximately 0.30 eV compared to the other graphene-based materials considered in this study. This detailed DFT study provides valuable data that can be used for the successful development of low-cost and efficient graphene-based catalysts for sodium–air battery systems operating with non-aqueous electrolyte.

We performed density functional theory analysis of heteroatom doped graphene as potential catalysts for rechargeable non-aqueous sodium–air batteries. Pyridinic nitrogen and boron doped graphene exhibited too low overpotential reaction pathways.     

Ristocetin and botrocetin involve two distinct domains of von Willebrand factor for binding to platelet membrane glycoprotein Ib.

We have evidence that ristocetin and botrocetin mediate binding of von Willebrand Factor (vWF) to platelet glycoprotein Ib (GPIb) through two distinct domains on the vWF molecule. This was established by using monoclonal antibodies (MAbs) to vWF and synthetic peptides derived from the sequence of vWF. MAb 322 and MAb NMC/vW4 both recognize native vWF as well as fragments containing the GPIb-binding domain of vWF, obtained with the following enzymes: trypsin (116 kDa), V-8 protease (SpIII, 320 kDa) and V-8 protease plus subtilisin (33-28 kDa). Nevertheless, the lack of reciprocal displacement between the two MAbs in experiments of competitive inhibition for binding to vWF demonstrate that their respective epitopes are separate. Both MAbs inhibit 125I-vWF binding to platelet membrane GPIb and vWF-dependent platelet agglutination induced by ristocetin. However, only MAb NMC/vW4 inhibits these functions in the presence of botrocetin and when ristocetin-induced platelet agglutination is inhibited by MAb 322, botrocetin is still able to restore the agglutination. The involvement of two distinct domains of vWF for binding to GPIb in the presence of ristocetin or botrocetin was confirmed in experiments of binding of 125I-vWF to platelets using a competitor synthetic peptides corresponding to the GPIb binding domain of vWF (Cys 474 to Pro 488 and Ser 692 to Pro 708). At a final concentration of 2.5 mM both peptides inhibit more than 90% of the binding of vWF to ristocetin-treated platelets but are unable to modify this binding in the presence of botrocetin. In conclusion our data suggest that botrocetin and ristocetin involve distinct sites on vWF for binding to GPIb.