Structure of an endogenous yeast 26S proteasome reveals two major conformational states.

The eukaryotic proteasome mediates degradation of polyubiquitinated proteins. Here we report the single-particle cryoelectron microscopy (cryo-EM) structures of the endogenous 26S proteasome from Saccharomyces cerevisiae at 4.6- to 6.

Infantile spinal muscular atrophy with respiratory distress type I presenting without respiratory involvement: Novel mutations and review of the literature.

Spinal muscular atrophy with respiratory distress type 1 (SMARD1), also known as distal spinal muscular atrophy 1 (DSMA1) or distal hereditary motor neuropathies type 6 (dHMN6), is a rare autosomal recessive motor neuron disorder that affects infants and is characterized by diaphragmatic palsy, distal muscular weakness and muscle atrophy. The disease is caused by mutations in the gene encoding immunoglobulinm-binding protein 2 (IGHMBP2). We present a female child with novel compound heterozygous mutations in IGHMBP2 gene c.

RhesusBase PopGateway: Genome-Wide Population Genetics Atlas in Rhesus Macaque.

Although population genetics studies have significantly accelerated the evolutionary and functional interrogations of genes and regulations, limited polymorphism data are available for rhesus macaque, the model animal closely related to human. Here, we report the first genome-wide effort to identify and visualize the population genetics profile in rhesus macaque. On the basis of the whole-genome sequencing of 31 independent macaque animals, we profiled a comprehensive polymorphism map with 46,146,548 sites.

miR-373 Inhibits Glioma Cell U251 Migration and Invasion by Down-Regulating CD44 and TGFBR2.

Glioblastoma multiforme (GBM) is the most malignant glioma, unveiling the underlying mechanisms of its aggressiveness could promote the discovery of potential targets for effective treatment. MicroRNAs (miRNAs) are important participants in both development and disease, its involvement in cancers has long been recognized. In this study, we investigated the role of miRNA-373 (miR-373) in GBM cell line U251, demonstrated that although miR-373 does not affect cell growth of U251, it inhibits migration and invasion of U251.

[Prevalence of HIV infection and syphilis, sexual behaviors and awareness of HIV/AIDS related knowledge among men who have sex with men in China: a Meta-analysis of data collected from 2010 to 2013].

Objective: To understand the time and area specific prevalence of HIV infection and syphilis, sexual behaviors and awareness of HIV/AIDS related knowledge among men who have sex with men (MSM) in the mainland of China during 2010-2013.

Methods: All the published academic papers on the prevalence of HIV infection and syphilis among MSM in the mainland of China from 2010 to 2013 were collected from CNKI, Wanfang and PubMed databases. Meta-analysis was performed by using software Stata 12.

Diagnostic value of the radiographic muscle-to-bone thickness ratio between the pronator quadratus and the distal radius at the same level in undisplaced distal forearm fracture.

Purpose: To investigate the value of the muscle-to-bone ratio (MBR), which is the ratio between the maximum pronator quadratus thickness (mPQT) and the distal radial thickness (DRT) at the same level, in comparison with mPQT in the diagnosis of undisplaced fractures in distal forearm (FDF) on radiographs.

Material And Methods: This study was conducted with 210 wrists of 210 volunteers (79 male, 131 female) and 106 wrists of 106 patients with acute undisplaced FDF (53 male, 53 female). The mPQT was measured on lateral radiographs, and the MBR was calculated for each wrist.

The 11S Proteasome Subunit PSME3 Is a Positive Feedforward Regulator of NF-κB and Important for Host Defense against Bacterial Pathogens.

The NF-κB pathway plays important roles in immune responses. Although its regulation has been extensively studied, here, we report an unknown feedforward mechanism for the regulation of this pathway by Toll-like receptor (TLR) ligands in macrophages. During bacterial infections, TLR ligands upregulate the expression of the 11S proteasome subunit PSME3 via NF-κB-mediated transcription in macrophages.

Design and characterization of human exposure to generated sulfate and soot particles in a pilot chamber study.

Unlabelled: A number of literatures have documented adverse health effects of exposure to fine particulate matter (PM2.5), and secondary sulfate aerosol and black carbon may contribute to health impacts of PM2.5 exposure.

Free-standing few-layered graphene oxide films: selective, steady and lasting permeation of organic molecules with adjustable speeds.

A variety of small molecules with diameters around 1 nm possess a range of functions, such as antibiotic, antimicrobic, anticoagulant, pesticidal and chemotherapy effects, making these molecules especially useful in various applications ranging from medical treatment to environmental microbiological control. However, the long-term steady delivery (release or permeation) of these small molecules with adjustable and controllable speeds has remained an especially challenging task. In this study, we prepared covalently cross-linked free-standing few-layered GO films using a layer-by-layer technique in combination with photochemical cross-linkages, and achieved a controlled release of positively charged, negatively charged, and zwitterionic small molecules with adjustable and controllable speeds.

Novel ATM mutations with ataxia-telangiectasia.

Ataxia telangiectasia is an autosomal recessive multisystem disorder characterized by progressive cerebellar ataxia with onset in childhood, oculocutaneous telangiectasia, increased serum alpha-fetoprotein, immunodeficiency, chromosomal instability, and radiation hypersensitivity. Ataxia-telangiectasia mutated gene (ATM) is one of the known genes to be associated with ataxia telangiectasia. We reported the clinical and genetic findings of three early-onset Chinese patients who demonstrated ataxia, oculomotor apraxia, choreoathetosis, myoclonus and telangiectasia of eyes.

Efficacy of 3D conformal thoracic radiotherapy for extensive-stage small-cell lung cancer: A retrospective study.

The aim of the present study was to evaluate the effect of 3-dimensional conformal thoracic radiotherapy (TRT) on extensive-stage small-cell lung cancer (ES-SCLC). A total of 165 patients with ES-SCLC were enrolled in the present study, including 82 patients receiving chemotherapy combined with TRT (the ChT/TRT group) and 83 patients receiving chemotherapy alone (the ChT group). The overall survival (OS) and progression-free survival (PFS) rates were compared between the ChT/TRT and ChT groups, and the prognostic factors for OS rate were identified.

PI3K/AKT/mTOR/p70S6K Pathway Is Involved in Aβ25-35-Induced Autophagy.

Disruption or deregulation of the autophagy system has been implicated in neurodegenerative disorders such as Alzheimer's disease (AD). Aβ plays an important role in this autophagic system. In many cases, autophagy is regulated by the phosphatidylinositol 3-phosphate kinase/AKT/mammalian target of rapamycin/p70 ribosomal protein S6 kinase (PI3K/AKT/mTOR/p70S6K) signaling pathway.

Upregulation of CCL2 via ATF3/c-Jun interaction mediated the Bortezomib-induced peripheral neuropathy.

Bortezomib (BTZ) is a frequently used chemotherapeutic drug for the treatment of refractory multiple myeloma and hematological neoplasms. The mechanism by which the administration of BTZ leads to painful peripheral neuropathy remains unclear. In present study, we found that application of BTZ at 0.

Marinobacter aromaticivorans sp. nov., a polycyclic aromatic hydrocarbon-degrading bacterium isolated from sea sediment.

A rod-shaped, Gram-stain-negative, slightly halotolerant bacterium, designated strain D15-8PT, was isolated from a sediment sample from the South China Sea. The strain could grow in NaCl concentrations ranging from 0.5 % to 10 % (w/v) (optimum 0.

Celastrol induces cell cycle arrest by MicroRNA-21-mTOR-mediated inhibition p27 protein degradation in gastric cancer.

Objective: Celastrol has anti-cancer effects by increase of apoptosis of gastric cancer cells. However, its role in gastric cancer cell cycle is still unclear. The aim of this study was to investigate the effect and mechanism of celastrol on gastric cancer cell cycle.

Large-scale genomic analyses link reproductive aging to hypothalamic signaling, breast cancer susceptibility and BRCA1-mediated DNA repair.

Menopause timing has a substantial impact on infertility and risk of disease, including breast cancer, but the underlying mechanisms are poorly understood. We report a dual strategy in ∼70,000 women to identify common and low-frequency protein-coding variation associated with age at natural menopause (ANM). We identified 44 regions with common variants, including two regions harboring additional rare missense alleles of large effect.

Th1-, Th2-, and Th17-associated cytokine expression in hypopharyngeal carcinoma and clinical significance.

Th0 cells differentiate into Th1 or Th2 depending on multiple transcription factors acting on specific time points to regulate gene expression. Th17 cells, a subset of IL-17-producing T cells distinct from Th1 or Th2 cells, have been described as key players in inflammation and autoimmune diseases as well as cancer development. In the present study, 53 patients with hypopharyngeal cancer were included.

Trans-ancestry genome-wide association study identifies 12 genetic loci influencing blood pressure and implicates a role for DNA methylation.

We carried out a trans-ancestry genome-wide association and replication study of blood pressure phenotypes among up to 320,251 individuals of East Asian, European and South Asian ancestry. We find genetic variants at 12 new loci to be associated with blood pressure (P = 3.9 × 10(-11) to 5.

Characterization of carbapenem-resistant Acinetobacter baumannii isolates in a Chinese teaching hospital.

Carbapenem-resistant Acinetobacter baumannii (CRAB) presents a serious therapeutic and infection control challenge. In this study, we investigated the epidemiological and molecular differences of CRAB and the threatening factors for contributing to increased CRAB infections at a hospital in western China. A total of 110 clinical isolates of A.

Solvent-free synthesis of crystalline metal phosphate oxalates with a (4,6)-connected fsh topology.

Two new organically templated manganese phosphate oxalates were synthesized under solvent-free conditions. They have different three-dimensional structures with a (4,6)-connected fsh topology. It is interesting that the amine molecules can reverse the structure-building roles of the metal phosphate skeleton and metal oxalate substructure for formation of their fsh-type frameworks.

A mechanically driven form of Kirigami as a route to 3D mesostructures in micro/nanomembranes.

Assembly of 3D micro/nanostructures in advanced functional materials has important implications across broad areas of technology. Existing approaches are compatible, however, only with narrow classes of materials and/or 3D geometries. This paper introduces ideas for a form of Kirigami that allows precise, mechanically driven assembly of 3D mesostructures of diverse materials from 2D micro/nanomembranes with strategically designed geometries and patterns of cuts.

Improved imputation of low-frequency and rare variants using the UK10K haplotype reference panel.

Imputing genotypes from reference panels created by whole-genome sequencing (WGS) provides a cost-effective strategy for augmenting the single-nucleotide polymorphism (SNP) content of genome-wide arrays. The UK10K Cohorts project has generated a data set of 3,781 whole genomes sequenced at low depth (average 7x), aiming to exhaustively characterize genetic variation down to 0.1% minor allele frequency in the British population.

Establishing a reentry procedure for human immunodeficiency virus screening-reactive donors in China.

Background: Screening of blood donors for antibody to human immunodeficiency virus Types 1 and 2 (anti-HIV-1/2) and/or HIV nucleic acid test (NAT) is a well-established venue to prevent HIV transfusion-transmitted disease. However, with the current available technologies, HIV testing may result in donor loss due to false-positive results. This study intended to establish a donor reentry procedure for HIV screening-reactive donors in China.