Strong protective effect of the APOL1 p.N264K variant against G2-associated focal segmental glomerulosclerosis and kidney disease

African Americans have a significantly higher risk of developing chronic kidney disease, especially focal segmental glomerulosclerosis -, than European Americans. Two coding variants (G1 and G2) in the APOL1 gene play a major role in this disparity. While 13% of African Americans carry the high-risk recessive genotypes, only a fraction of these individuals develops FSGS or kidney failure, indicating the involvement of additional disease modifiers. Here, we show that the presence of the APOL1 p.N264K missense variant, when co-inherited with the G2 APOL1 risk allele, substantially reduces the penetrance of the G1G2 and G2G2 high-risk genotypes by rendering these genotypes low-risk. These results align with prior functional evidence showing that the p.N264K variant reduces the toxicity of the APOL1 high-risk alleles. These findings have important implications for our understanding of the mechanisms of APOL1-associated nephropathy, as well as for the clinical management of individuals with high-risk genotypes that include the G2 allele

GRADE Summary of Findings Tabellen und Evidenzprofile: Detaillierte Anleitung für Time-to-event Variablen

Glutamate excitotoxicity is associated with a wide range of neurodegenerative disorders and also seems to be involved in the pathology of demyelinating disorders such as multiple sclerosis (MS). Cuprizone-induced toxic demyelination shows clear characteristics of MS such as demyelination and axonal damage without the involvement of the innate immune system. In this study, we have evaluated glutamate signaling during cuprizone-induced demyelination in the white and gray matter of mouse brain by studying the expression of ionotropic and metabotropic glutamate-receptors and -transporters by Affymetrix gene array analysis, followed by real-time PCR and western blot analysis. Cellular localization of glutamate transporters was investigated by fluorescence double-labeling experiments. Comparing white and gray matter areas, the expression of glutamate receptors was region-specific. Among NMDA receptor subunits, NR2A was up-regulated in the demyelinated corpus callosum (CC), whereas the metabotropic glutamate receptor mGluR2 was down-regulated in demyelinated gray matter. Glutamate-aspartate transporter (GLAST) co-localizing with GFAP+ astrocytes was increased in both demyelinated CC and telencephalic cortex, whereas Slc1a4 transporter was up-regulated only in CC. Our data indicate that cuprizone treatment affects glutamate-receptors and -transporters differently in gray and white matter brain areas revealing particularly regulation of GLAST and Slc1a4 compared with other genes. This might have an important influence on brain-region selective sensitivity to neurotoxic compounds and the progression of demyelination as has been reported for MS and other demyelinating neurological diseases. © 2013 Elsevier GmbH

Cultural acceptability and personal willingness of Iranian students toward cadaveric donation

Cadaver dissection stands as a crucial component in medical curricula around the world, although computer-based multimedia programs have been introduced in order to replace the need for cadaver donations. Due to a decrease in the number of unclaimed bodies and rather few donations, there is an insufficient number of cadavers for anatomical studies in Iran. This study was carried out to evaluate medical students' awareness and willingness regarding body donation in Kashan University of Medical Sciences, Iran. In this study, a questionnaire was designed to focus on the cultural acceptability and personal willingness to donate one's body after death. Students from the university's anatomy classes (n = 331) participated in this study. Seventy-seven percent of the students expressed their agreement toward the idea of utilizing body donation services, though only 25.4% of participants were willing to donate their own bodies. None of the demographic factors were associated with cultural acceptability or personal willingness towards body donation. These findings indicated that besides “payment”, other factors were associated with students' willingness to become donors. All factors of awareness except “previous awareness of organization” were associated with cultural acceptability. In this study, students suggested that encouraging people to register for body donation using mass media (25.6%) and teaching students to respect cadavers in the dissection environment (24.8%) were the best solutions for addressing the lack of cadavers. These findings indicated that a lack of awareness about body donation might be the main factor responsible for unwillingness towards body donation; therefore, improving the public's awareness and addressing the willingness of students regarding body donation may help overcome the current lack of donated cadavers. Anat Sci Educ 10: 120–126. © 2016 American Association of Anatomists

Some challenges in the first-principles modeling of structures and processes in electrochemical energy storage and transfer

In spite of the strong relevance of electrochemical energy conversion and storage, the atomistic modeling of structures and processes in electrochemical systems from first principles is hampered by severe problems. Among others, these problems are associated with the theoretical description of the electrode potential, the characterization of interfaces, the proper treatment of liquid electrolytes, changes in the bulk structure of battery electrodes, and limitations of the functionals used in first-principles electronic structure calculations. We will illustrate these obstacles, but also indicate strategies to overcome them