Variable sources of Bk virus in renal allograft recipients

BK virus is the causative agent of polyomavirus-associated nephropathy, a major cause of kidney transplant failure affecting 1%-10% of recipients. Previous studies that investigated the viral source on the kidney recipient pointed that the donor is implicated in the origin of human polyomavirus BK (BKPyV) infection in recipients, but giving the low genetic variability of BKPyV this subject is still controversial. The aim of this study was to determine if BKPyV replicating in kidney recipients after transplantation is always originated from the donor. Urine and blood samples from 68 pairs of living donors and kidney recipients who underwent renal transplantation from August 2010-September 2011 were screened for BKPyV by real time polymerase chain reaction. Only three recipients presented viremia. When both donors and recipients were BKPyV positive, a larger fragment of VP1 region was obtained and sequenced to determine the level of similarity between them. A phylogenetic tree was built for the 12 pairs of sequences obtained from urine and high level of similarity among all sequences was observed, indicating that homology inferences for donor and recipient viruses must be cautiously interpreted. However, a close inspection on the donor-recipient pairs sequences revealed that 3 of 12 pairs presented considerably different viruses and 4 of 12 presented mixed infection, indicating that the source of BKPyV infection is not exclusively derived from the donor. We report that about 60% of the renal recipients shed BKPyV genetically distinct from the donor, confronting the accepted concept that the donor is the main source of recipients’ infection.     

Dysregulation of TDP‐43 intracellular localization and early onset ALS are associated with a TARDBP S375G variant

We investigated the Central Nervous System (CNS) and skeletal muscle tissue from A woman was clinically diagnosed with amyotrophic lateral sclerosis (ALS) at the age of 22. Neuropathologic evaluation showed upper and lower motor neuron loss, corticospinal tract degeneration and skeletal muscle denervation. Analysis of the patient's Deoxyribonucleic acid (DNA) revealed a AGT>GGT change resulting in an S375G substitution in the C‐terminal region of TDP‐43. This variant was previously reported as being benign. Considering the early onset and severity of the disease in this patient, we tested the effects of this genetic variant on TDP‐43 localization, pre‐mRNA splicing activity and toxicity, in parallel with the effects on known neighboring disease‐associated mutations. In cell lines, expressed in culture, S375G TDP‐43 appeared to be more significantly localized in the nucleus and to exert higher toxicity than wild‐type TDP‐43. Strikingly, a phosphomimic mutant at the same residue (S375E) showed a strong tendency to accumulate in the cytoplasm, especially under stress conditions, and molecular dynamics simulations suggest that phosphorylation of this residue can disrupt TDP‐43 intermolecular interactions. The results of the current study highlight the importance of phosphorylation and regulation of TDP‐43 nuclear‐cytoplasmic shuttling/redistribution, in relation to the pathogenetic mechanisms involved in different forms of ALS.     

Interface Engineering for Perovskite Solar Cells Based on 2D-Materials: A Physics Point of View

The last decade has witnessed the advance of metal halide perovskites as a promising low-cost and efficient class of light harvesters used in solar cells (SCs). Remarkably, the efficiency of lab-scale perovskite solar cells (PSCs) reached a power conversion efficiency of 25.5% in just ~10 years of research, rivalling the current record of 26.1% for Si-based PVs. To further boost the performances of PSCs, the use of 2D materials (such as graphene, transition metal dichalcogenides and transition metal carbides, nitrides and carbonitrides) has been proposed, thanks to their remarkable optoelectronic properties (that can be tuned with proper chemical composition engineering) and chemical stability. In particular, 2D materials have been demonstrated as promising candidates for (i) accelerating hot carrier transfer across the interfaces between the perovskite and the charge extraction layers; (ii) improving the crystallization of the perovskite layers (when used as additives in the precursor solution); (iii) favoring electronic bands alignment through tuning of the work function. In this mini-review, we discuss the physical mechanisms underlying the increased efficiency of 2D material-based PSCs, focusing on the three aforementioned effects.     

A multi-state survey of videotaping practices for major trauma resuscitations.

The objective of this study was to determine the prevalence and problems, both perceived and actual, associated with videotaping major trauma resuscitations. A cross-sectional two-part survey of trauma centers was conducted. Part 1 determined demographic information and videotaping status. Part 2 asked trauma centers that were not doing videotaping (NVTCs) about their plans, past experience, and perceived problems. Videotaping trauma centers (VTCs) were asked about mechanics, responsibility, utilization, and problems. A total of 221 centers were surveyed; 20% VTCs, 70% NVTCs, and 10% NVTCs that had videotaped in the past (PVTC). Among VTCs, 53% reported problems with videotaping including lack of personnel (40%) and time (40%) to administer the program. Videotaping, however, was found to be an effective quality improvement tool in 95% of the VTCs. Of the NVTCs, 70% perceived problems with implementing a videotaping program; these included medicolegal (34%) and patient confidentiality (22%) concerns. Of the PVTCs, 90% stated that they had problems with videotaping including lack of staff support (33%) and lack of personnel to assist with the program (24%). In conclusion, staff participation and adequate personnel outweigh medicolegal concerns as actual videotaping problems. Videotaping is perceived to be an effective performance improvement tool.     

Genotyping of the CCR5 chemokine receptor by isothermal NASBA amplification and differential probe hybridization.

The human CCR5 chemokine receptor functions as a coreceptor with CD4 for infection by macrophage-tropic isolates of human immunodeficiency virus type 1 (HIV-1). A mutated CCR5 allele which encodes a protein that does not function as a coreceptor for HIV-1 has been identified. Thus, expression of the wild-type and/or mutation allele is relevant to determining the infectability of patient peripheral blood mononuclear cells (PBMC) and affects disease progression in vivo. We developed a qualitative CCR5 genotyping assay using NASBA, an isothermal nucleic acid amplification technology. The method involves three enzymes and two oligonucleotides and targets the CCR5 mRNA, which is expressed in PBMC at a copy number higher than 2, the number of copies of DNA present encoding the gene. The single oligonucleotide set amplifies both alleles, and genotyping is achieved by separate hybridizations of wild-type- and mutation-specific probes directly to the single-stranded RNA amplification product. Assay sensitivity and specificity were demonstrated with RNAs produced in vitro from plasmid clones bearing the DNA encoding each allele. No detectable cross-reactivity between wild-type and mutation probes was found, and 50 copies of each allele were readily detectable. Analysis of patient samples found that 20% were heterozygous and 1% were homozygous for the CCR5 mutation. Thus, NASBA is a sensitive and specific means of rapidly determining CCR5 genotype and provides several technical advantages over alternative assay systems.