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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