Immunophenotyping in BK Virus Allograft Nephropathy Distinct from Acute Rejection

Differentiating BK virus nephropathy (BKVN) from acute rejection (AR) is crucial in clinical practice, as both of them have interstitial inflammation in the grafts. The purpose of the study is to describe the inflammatory cellular constituents of BKVN and to determine the clinical utility of immunophenotyping findings in distinguishing BKVN from AR. In addition, the expression of the HLA-DR was investigated. Sixty-five renal allograft recipients were included in this study, including 22 cases of BKVN, 31 cases of AR, and 12 cases of stable allograft. Immunostaining for infiltrating lymphocytes showed that the number of CD20 cells (P<0.001) and the percentages of CD3 (P<0.001), CD4 (P=0.004), CD8 (P=0.005), and CD20 (P=0.002) cells were all significantly different between BKVN and AR. Moreover, there were no statistically significant differences in tubule cell HLA-DR expression (P=0.156). This observation suggests that the number of CD20 cells and the percentages of CD3, CD4, CD8, and CD20 cells in renal biopsies would aid the distinction between BKVN and AR. On the other hand, the presence of HLA-DR upregulation may not only be specific for acute rejection but also be a response to BKVN

An Introduction to the China Rice Functional Genomics Program

The China Rice Functional Genomics Program (CRFGP) was initiated in 1999 by the Ministry of Science and Technology of China under the National Basic Sciences Initiative and was expected to last for an initial period of five years. The CRFGP involves 20 research groups from the Chinese Academy of Sciences and some major universities and focuses on the identification of genes controlling flowering, plant architecture, fertility, reproduction, metabolic controls and stress responses in rice through a combinatorial approach based on genetics, molecular biology and functional genomics as well as the generation of intellectual properties related to crop breeding and improvements. We will briefly describe the mission of the CRFGP as well as its recent progress

Tailoring single-atom FeN4 moieties as a robust heterogeneous catalyst for high-performance electro-Fenton treatment of organic pollutants

An iron single-atom catalyst, composed of robust FeN4 moieties anchored on a nitrogen-doped porous carbón matrix (Fe-SAC/NC), has been developed via a surfactant-coordinated metal-organic framework (MOF) approach for application in heterogeneous electro-Fenton (HEF) process. The cohesive interaction between the surfactant and MOF precursor enabled the formation of abundant and stable FeN4 moieties. The Fe-SAC/NC-catalyzed HEF allowed the complete degradation of 2,4-dichlorophenol with low iron leaching (1.2 mg L-1), being superior to nanoparticle catalyst synthesized without surfactant. The experiments and density functional theory (DFT) calculations demonstrated the dominant role of single-atom FeN4 sites to activate the electrogenerated H2O2 yielding ¿OH. The dense FeN4 moieties allowed harnessing the modulated electronic structure of the SAC to facilitate the electron transfer, whereas the adjacent pyrrolic N enhanced the adsorption of target organic pollutants. Moreover, the excellent catalysis, recyclability and viability of the Fe-SAC/NC were verified by successfully treating several organic pollutants even in urban wastewater

Genome-wide association analyses identify 143 risk variants and putative regulatory mechanisms for type 2 diabetes

Type 2 diabetes (T2D) is a very common disease in humans. Here we conduct a meta-analysis of genome-wide association studies (GWAS) with ~16 million genetic variants in 62,892 T2D cases and 596,424 controls of European ancestry. We identify 139 common and 4 rare variants associated with T2D, 42 of which (39 common and 3 rare variants) are independent of the known variants. Integration of the gene expression data from blood (n = 14,115 and 2765) with the GWAS results identifies 33 putative functional genes for T2D, 3 of which were targeted by approved drugs. A further integration of DNA methylation (n = 1980) and epigenomic annotation data highlight 3 genes (CAMK1D, TP53INP1, and ATP5G1) with plausible regulatory mechanisms, whereby a genetic variant exerts an effect on T2D through epigenetic regulation of gene expression. Our study uncovers additional loci, proposes putative genetic regulatory mechanisms for T2D, and provides evidence of purifying selection for T2D-associated variants.</p

The Prevalence of Immunologic Injury in Renal Allograft Recipients with De Novo Proteinuria

Post-transplant proteinuria is a common complication after renal transplantation; it is associated with reduced graft and recipient survival. However, the prevalence of histological causes has been reported with considerable variation. A clinico-pathological re-evaluation of post-transplant proteinuria is necessary, especially after dismissal of the term “chronic allograft nephropathy,” which had been considered to be an important cause of proteinuria. Moreover, urinary protein can promote interstitial inflammation in native kidney, whether this occurs in renal allograft remains unknown. Factors that affect the graft outcome in patients with proteinuria also remain unclear. Here we collected 98 cases of renal allograft recipients who developed proteinuria after transplant, histological features were characterized using Banff scoring system. Cox proportional hazard regression models were used for graft survival predictors. We found that transplant glomerulopathy was the leading (40.8%) cause of post-transplant proteinuria. Immunological causes, including transplant glomerulopathy, acute rejection, and chronic rejection accounted for the majority of all pathological causes of proteinuria. Nevertheless, almost all patients that developed proteinuria had immunological lesions in the graft, especially for interstitial inflammation. Intraglomerular C3 deposition was unexpectedly correlated with the severity of proteinuria. Moreover, the severity of interstitial inflammation was an independent risk factor for graft loss, while high level of hemoglobin was a protective factor for graft survival. This study revealed a predominance of immunological parameters in renal allografts with post-transplant proteinuria. These parameters not only correlate with the severity of proteinuria, but also with the outcome of the graft

Genome-wide association analyses identify 143 risk variants and putative regulatory mechanisms for type 2 diabetes

Type 2 diabetes (T2D) is a very common disease in humans. Here we conduct a meta-analysis of genome-wide association studies (GWAS) with ~16 million genetic variants in 62,892 T2D cases and 596,424 controls of European ancestry. We identify 139 common and 4 rare variants associated with T2D, 42 of which (39 common and 3 rare variants) are independent of the known variants. Integration of the gene expression data from blood (n = 14,115 and 2765) with the GWAS results identifies 33 putative functional genes for T2D, 3 of which were targeted by approved drugs. A further integration of DNA methylation (n = 1980) and epigenomic annotation data highlight 3 genes (CAMK1D, TP53INP1, and ATP5G1) with plausible regulatory mechanisms, whereby a genetic variant exerts an effect on T2D through epigenetic regulation of gene expression. Our study uncovers additional loci, proposes putative genetic regulatory mechanisms for T2D, and provides evidence of purifying selection for T2D-associated variants

Finishing the euchromatic sequence of the human genome

The sequence of the human genome encodes the genetic instructions for human physiology, as well as rich information about human evolution. In 2001, the International Human Genome Sequencing Consortium reported a draft sequence of the euchromatic portion of the human genome. Since then, the international collaboration has worked to convert this draft into a genome sequence with high accuracy and nearly complete coverage. Here, we report the result of this finishing process. The current genome sequence (Build 35) contains 2.85 billion nucleotides interrupted by only 341 gaps. It covers ∼99% of the euchromatic genome and is accurate to an error rate of ∼1 event per 100,000 bases. Many of the remaining euchromatic gaps are associated with segmental duplications and will require focused work with new methods. The near-complete sequence, the first for a vertebrate, greatly improves the precision of biological analyses of the human genome including studies of gene number, birth and death. Notably, the human enome seems to encode only 20,000-25,000 protein-coding genes. The genome sequence reported here should serve as a firm foundation for biomedical research in the decades ahead

Pion and kaon structure at the electron-ion collider

Understanding the origin and dynamics of hadron structure and in turn that of atomic nuclei is a central goal of nuclear physics. This challenge entails the questions of how does the roughly 1GeV mass-scale that characterizes atomic nuclei appear; why does it have the observed value; and, enigmatically, why are the composite Nambu-Goldstone (NG) bosons in quantum chromodynamics (QCD) abnormally light in comparison? In this perspective, we provide an analysis of the mass budget of the pion and proton in QCD; discuss the special role of the kaon, which lies near the boundary between dominance of strong and Higgs mass-generation mechanisms; and explain the need for a coherent effort in QCD phenomenology and continuum calculations, in exa-scale computing as provided by lattice QCD, and in experiments to make progress in understanding the origins of hadron masses and the distribution of that mass within them. We compare the unique capabilities foreseen at the electron-ion collider (EIC) with those at the hadron-electron ring accelerator (HERA), the only previous electron-proton collider; and describe five key experimental measurements, enabled by the EIC and aimed at delivering fundamental insights that will generate concrete answers to the questions of how mass and structure arise in the pion and kaon, the Standard Model's NG modes, whose surprisingly low mass is critical to the evolution of our Universe