The trans-ancestral genomic architecture of glycemic traits

Glycemic traits are used to diagnose and monitor type 2 diabetes and cardiometabolic health. To date, most genetic studies of glycemic traits have focused on individuals of European ancestry. Here we aggregated genome-wide association studies comprising up to 281,416 individuals without diabetes (30% non-European ancestry) for whom fasting glucose, 2-h glucose after an oral glucose challenge, glycated hemoglobin and fasting insulin data were available. Trans-ancestry and single-ancestry meta-analyses identified 242 loci (99 novel; P < 5 x 10(-8)), 80% of which had no significant evidence of between-ancestry heterogeneity. Analyses restricted to individuals of European ancestry with equivalent sample size would have led to 24 fewer new loci. Compared with single-ancestry analyses, equivalent-sized trans-ancestry fine-mapping reduced the number of estimated variants in 99% credible sets by a median of 37.5%. Genomic-feature, gene-expression and gene-set analyses revealed distinct biological signatures for each trait, highlighting different underlying biological pathways. Our results increase our understanding of diabetes pathophysiology by using trans-ancestry studies for improved power and resolution. A trans-ancestry meta-analysis of GWAS of glycemic traits in up to 281,416 individuals identifies 99 novel loci, of which one quarter was found due to the multi-ancestry approach, which also improves fine-mapping of credible variant sets.Peer reviewe

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

Candida Parapsilosis Total Hip Arthroplasty Infection: Case Report and Literature Review

A 71 year-old male with a history of diabetes mellitus and right total hip arthroplasty (THA), received a revision surgery on the acetabulum cup of the THA because of loosening. The intraoperative culture yielded Candida parapsilosis. It was regarded as contamination initially. The patient had remained asymptomatic for 4 years after the revision surgery. The radiographs showed no evidence of loosening and the blood inflammatory markers were normal. The only abnormal finding was two subcutaneous swellings over the surgical scar. The patient then presented with right hip pain on walking and low-grade fever. A course of fluconazole had been given for 6 months, but the infection did not improve. Eventually, an excision arthroplasty of the right hip was performed. This case illustrates the rarity and the indolent pattern of presentation of fungal prosthetic infection. High index of suspicion and prompt treatment were needed. Literature on fungal prosthetic infection was also reviewed

Anti-inflammatory effects of gossypol on human lymphocytic Jurkat cells via regulation of MAPK signaling and cell cycle

[[abstract]]Gossypol, a natural polyphenolic compound extracted from cottonseed oil, has been reported to possess pharmacological properties via modulation cell cycle and immune signaling pathway. However, whether gossypol has anti-inflammatory effects against phytohemagglutinin (PHA)-induced cytokine secretion in T lymphocytes through similar mechanism remains unclear. Using the T lymphocytes Jurkat cell line, we found that PHA exposure caused dramatic increase in interleukin-2 (IL-2) mRNA expression as well as IL-2 secretion. All of these PHA-stimulated reactions were attenuated in a dose-dependent manner by being pretreated with gossypol. However, gossypol did not show any in vitro cytotoxic effect at doses of 5-20 μM. As a possible mechanism underlying gossypol action, such as pronounced suppression IL-2 release, robust decreased PHA-induced phosphorylation of p38 and c-Jun N-terminal kinase expressions was found with gossypol pretreatment, but not significant phosphorylation of extracellular signal-regulated kinase expression. Furthermore, gossypol could suppress the Jurkat cells' growth, which was associated with increased percentage of G1/S phase and decreased fraction of G2 phase in flow cytometry test. We conclude that gossypol exerts anti-inflammatory effects probably through partial attenuation of mitogen-activated protein kinase (phosphorylated JNK and p38) signaling and cell cycle arrest in Jurkat cells