The 1000 Genomes Project set out to provide a comprehensive description of common human genetic variation by applying whole-genome sequencing to a diverse set of individuals from multiple populations. Here we report completion of the project, having reconstructed the genomes of 2,504 individuals from 26 populations using a combination of low-coverage whole-genome sequencing, deep exome sequencing, and dense microarray genotyping. We characterized a broad spectrum of genetic variation, in total over 88 million variants (84.7 million single nucleotide polymorphisms (SNPs), 3.6 million short insertions/deletions (indels), and 60,000 structural variants), all phased onto high-quality haplotypes. This resource includes >99% of SNP variants with a frequency of >1% for a variety of ancestries. We describe the distribution of genetic variation across the global sample, and discuss the implications for common disease studies.

Adaptation to specialized diets often requires modifications at both genomic and microbiome levels. We applied a hologenomic approach to the common vampire bat (Desmodus rotundus), one of the only three obligate blood-feeding (sanguivorous) mammals, to study the evolution of its complex dietary adaptation. Specifically, we assembled its high-quality reference genome (scaffold N50=26.9 Mb, contig N50=36.6 Kb) and gut metagenome, and compared them against those of insectivorous, frugivorous, and carnivorous bats. Our analyses showed i) a particular common vampire bat genomic landscape regarding integrated viral elements, ii) a dietary and phylogenetic influence on gut microbiome taxonomic and functional profiles, and iii) that both genetic elements harbor key traits related to the nutritional (e.g. vitamins and lipids shortage) and non-nutritional challenges (e.g. nitrogen waste and osmotic homeostasis) of sanguivory. These findings highlight the value of a holistic study of both host and microbiota when attempting to decipher adaptations underlying radical dietary lifestyles.

ObjectiveWhether automated peritoneal dialysis (APD) is a feasible strategy for urgent-start peritoneal dialysis (PD) therapy during the break-in period remains unclear. This study was conducted to compare the efficacy as well as complications among three PD modes during the break-in period.MethodsNinety-six patients treated with urgent-start PD after catheterization were retrospectively analyzed. Patients were divided into three groups, incremental continuous ambulatory PD (CAPD) group (n = 26); APD group (n = 42); and APD–CAPD group (n = 28). Clinical parameters at the end of the break-in period and 1 month after the initiation of PD treatment were collected and analyzed.ResultsCompared with the traditional incremental CAPD, APD and APD–CAPD were superior as they could effectively remove small-molecule uremic toxins and correct electrolyte imbalance (P < 0.05), while did not increase the incidence of early complications during the break-in period (P > 0.05). However, APD led to a significant decline in albumin and pre-albumin, as compared with APD–CAPD and CAPD (P < 0.05). A PD strategy consisting 6 days of APD and 3 days of CAPD showed a great advantage in preventing excessive protein loss. There were no significant differences in all tested biochemical parameters among the three groups at 1 month after treatment (all P > 0.05).ConclusionApplication of APD for urgent-start PD during the break-in period is feasible. A combination of APD and CAPD regimens seems to be a more reasonable mode.

Smads are the key intermediates of canonical transforming growth factor-beta (TGF-β) signaling. These intermediates are divided into three distinct subgroups based on their role in TGF-β family signal transduction: Receptor-regulated Smads (R-Smads) 1, 2, 3, 5 and 8, common Smad4, and inhibitory Smads6 and 7. TGF-β signaling through Smad pathway involves phosphorylation, ubiquitination, sumoylation, acetylation, and protein-protein interactions with mitogen-activated protein kinases, PI3K-Akt/PKB, and Wnt/GSK-3. Several studies have suggested that upregulation or downregulation of TGF-β/Smad signaling pathways may be a pathogenic mechanism in the progression of chronic kidney disease. Smad2 and 3 are the two major downstream R-Smads in TGF-β-mediated renal fibrosis, while Smad7 also controls renal inflammation. In this review, we characterize the role of Smads in kidney disease, describe the molecular mechanisms, and discuss the potential of Smads as a therapeutic target in chronic kidney disease.

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Purpose: The association of serum elabela (ELA) and apelin with the progression of chronic kidney disease (CKD) is unknown. We determined if serum ELA and apelin levels were associated with CKD stage. Methods: This observational study involved 60 CKD patients and 20 healthy, age-, race-, and gender-matched controls. The participants were grouped according to renal function as follows: normal control group, CKD1 group (stage-1 CKD, 20 patients), CKD3 group (stage-3 CKD, 20 patients), and CKD5 group (stage-5 CKD, 20 patients) in accordance with the Kidney Disease Outcomes-Quality Initiative criteria. We recorded the demographic, clinical, and biochemical data of all participants. Serum ELA and apelin levels were measured using commercially available enzyme-linked immunosorbent assays. Results: Serum ELA levels gradually and significantly declined with decreases in the estimated glomerular filtration rate (eGFR). Serum ELA showed significant negative correlations with serum creatinine (r ¼ À0.529, p < .001), blood urea nitrogen (r ¼ À0.575, p < .001), systolic blood pressure (r ¼ À0.455, p < .001), and diastolic blood pressure (r ¼ À0.450, p < .001), and significant positive correlations with hemoglobin (r ¼ 0.523, p < .001) and eGFR (r ¼ 0.728, p < .001). Multiple regression analysis showed that eGFR independently influenced serum ELA levels. No significant association was found between serum apelin levels and CKD progression. Conclusion: In CKD patients, serum ELA levels decreased with decreasing eGFR. This finding may provide a new target for the prediction, diagnosis, and staging of CKD.

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In order to further elucidate the potential correlations and treatments of IgA nephropathy (IgAN) and hypertensive nephropathy (HT), bioinformatics analysis of IgAN and HT was performed. The mRNA expression profiles of human renal biopsy samples from patients with IgAN, patients with HT and pre-transplant healthy living controls (LD) were downloaded from the Gene Expression Omnibus database. Then, the differentially expressed genes (DEGs) were identified and functions of DEGs were analyzed. Finally, the regulatory networks containing DEGs and related-transcription factors (TFs) were constructed using Cytoscape software. When compared with the LD group, 134 and 188 DEGs were obtained in the IgAN and HT groups, respectively. A total of 39 genes were altered in the HT group when compared with the IgAN group. In addition, 66 genes were shared in the IgAN and HT groups when compared with the LD group, 6 of which [early growth response 1, activating transcription factor 3, nuclear receptor subfamily 4 group A member 2 (NR4A2), NR4A1, v-maf avian musculoaponeurotic fibrosarcoma oncogene homolog F and Kruppel like factor 6] were identified as TFs. In addition, DEGs including interleukin (IL) 1 receptor antagonist, collagen type 4 α2 chain, IL8, FBJ murine osteosarcoma viral oncogene homolog and somatostatin were enriched in a number of inflammation-associated biological processes, and DEGs including structural maintenance of chromosomes protein 3, v-crk avian sarcoma virus CT10 oncogene homolog and myosin 6 were enriched in non-inflammation-associated biological processes. Therefore, the differentially expressed TF genes and the genes associated with inflammation may be effective as potential therapeutic targets for IgAN and HT.