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

Optimization of hot extrusion process parameters for 7075 aluminum alloy rims based on HyperXtrude

Aluminum alloy has the characteristics of light weight, high strength, corrosion resistance, easy forming, etc., and is widely used in manufacturing industry. The extrusion speed of aluminum alloy rim is not uniform, which affects the mechanical properties of the product. In order to solve these 1problems, the finite element analysis model of hot extrusion of aluminum alloy profiles was established in HyperXtrude software. The influences of different bar diameters, hot extrusion velocity, bar preheating temperature, die temperature and extrusion cylinder temperature on velocity difference and maximum extrusion pressure at the exit were analyzed. The results show that the designed hot extrusion rim die meets the requirements of strength and deformation, and the best extrusion process parameters of 7075 aluminum alloy rim profiles in improving profile quality and reducing energy consumption are obtained by Taguchi test gray correlation method

Mucormycosis in renal transplant recipients: review of 174 reported cases

Abstract Background Mucormycosis is a highly lethal fungal infection especially in immunocompromised individuals. Methods In order to review the epidemiology, diagnosis, and treatment of mucormycosis in renal transplant recipients we searched publications of mucormycosis cases in renal transplant recipients in PUBMED database up to December 2015. Results A total of 174 cases in renal transplant recipients were included in this review. Most of the cases (76%) were male. Major underlying diseases were diabetes mellitus (43.1%). Rhinocerebral was the most common site of infection (33.3%). Rhizopus species was the most frequent fungus (59.1%) in patients with pathogen identified to species level. The mortality rates of disseminated mucormycosis (76.0%) and graft renal (55.6%) were higher than infection in other sites. The overall survival in patients received surgical debridement combined with amphotericin B/posaconazole (70.2%) was higher than those who received antifungal therapy alone (32.4%), surgery alone (36.4%) or without therapy (0%) (p < 0.001). The overall survivals in patients receiving posaconazole and lipid amphoterincin B were higher than that receiving deoxycholate formulation (92.3% and 73.4% vs 47.4%). Conclusions Mucormycosis is a severe infection in renal transplant recipients. Surgical debridement combined with antifungals, especially liposomal amphotericin B and posaconazole, can significantly improve patient’s overall survival

5-Aza-2’-deoxycytidine in the medial prefrontal cortex regulates alcohol-related behavior and Ntf3-TrkC expression in rats - Fig 4

<p>(A) Schematic illustrations and representative photomicrographs of the intracranial cannula infusion sites in the mPFC. 5-Aza-dc infusion decreased alcohol intake (B) and alcohol preference (C) in alcohol-exposure rats, corresponding to the reduced blood alcohol levels (F). (D) The alcohol preference in water- and alcohol-exposure rats at 1d and 5d after 5-Aza-dc treatment. (E) 5-Aza-dc did not affect the total fluid intake. * p < 0.05, ** p < 0.01, *** p < 0.001, **** p < 0.0001 and p < 0.05 indicate differences from the Alcohol+DMSO group. #### p < 0.0001, differences compared to Water+DMSO group. (G) 5-Aza-dc had no effect on the locomotor activity of alcohol-exposure rats. (H) 5-Aza-dc decreased the exploration time in the center in alcohol-exposure rats. * p < 0.05, *** p < 0.001, differences compared to the Water+DMSO group; p < 0.05, differences compared to the Alcohol+DMSO group; ## p < 0.01, differences compared to Water+5-Aza-dc group; n = 8/group.</p

Identification of a novel glycolysis-related prognosis risk signature in triple-negative breast cancer

IntroductionTriple-negative breast cancer (TNBC) is a particularly aggressive cluster of breast cancer characterized by significant molecular heterogeneity. Glycolysis is a metabolic pathway that is significantly associated with cancer progression, metastasis, recurrence and chemoresistance. However, the potential roles of glycolysis-related genes in TNBC remain unclear.MethodsIn the present study, we identified 108 glycolysis-related differentially expressed genes (DEGs) between breast cancer (BRCA) tumor tissues and normal tissues, and we divided patients into two different clusters with significantly distinct molecular characteristics, clinicopathological features, prognosis, immune cell infiltration and mutation burden. We then constructed a 10-gene signature that classified all TNBCs into low- and high-risk groups.ResultsThe high-risk group had significantly lower survival than the low-risk group, which implied that the risk score was an independent prognostic indicator for TNBC patients. Consequently, we constructed and validated a prognostic nomogram, which accurately predicted individual overall survival (OS) of TNBC. Moreover, the risk score predicted the drug sensitivity of chemotherapeutic agents and immunotherapy for TNBC patients.DiscussionThe present comprehensive analysis of glycolysis-related DEGs in TNBC provides new methods for prognosis prediction and more effective treatment strategies

Effects of 5-Aza-dc and alcohol on DNMTs and Ntf3/TrkC expressions in the mPFC.

<p>Fig 5A shows representative immunoblots and total protein image. 5-Aza-dc decreased the protein level of DNMT1 (B), whereas it reversed the alcohol-induced overexpression of DNMT3A (C) and DNMT3B (D). 5-Aza-dc prevented the Ntf3 reduction induced by chronic alcohol exposure (E) but had no effect on TrkC (F). (G) Differential expression of mRNA for DNMTs, Ntf3 and TrkC. * p < 0.05, ** p < 0.01, *** p < 0.001, differences compared to the Water+DMSO group; # p < 0.05, ## p < 0.01, ### p < 0.01, differences compared to the other corresponding groups; n = 8/group.</p

General experimental design.

<p>In experiment 1 (A), rats were randomly divided into an alcohol-exposure group (n = 12) and a water-exposure group (n = 12). After baseline drinking, alchol-exposure rats underwent TBCT for 5 consecutive days, and water-exposure rats underwent TBCT at the first and fifth day. Alcohol-exposure group then received alcohol solution as the only liquid source for 5 weeks and water-exposure group received water ad libitum. Next, rats were evaluated for alcohol drinking by TBCT for another 5 days. Then animals were decapitated immediately and brain tissues were collected. In experiment 2 (B), all rats underwent the same protocol as which in experiment 1. Then, rats were randomly divided into four groups, Water+DMSO, Water+5-Aza-dc, Alcohol+DMSO, and Alcohol+5-Aza-dc (n = 8/group) groups, and received mPFC stereotactic surgery followed by recovery for a total of 9 days. Subsequently, rats underwent bilateral intra-mPFC injections of 5-Aza-dc or DMSO at days 1, 3, and 5 followed by 6% (v/v) alcohol or water exposure 30 min later. Alcohol intake and TBCT were monitored every day. After the last TBCT, mPFC were collected.</p

A Population-Based Study of Four Genes Associated with Heroin Addiction in Han Chinese

<div><p>Recent studies have shown that variants in FAT atypical cadherin 3 (<i>FAT3</i>), kinectin 1 (<i>KTN1</i>), discs large homolog2 (<i>DLG2</i>) and deleted in colorectal cancer (<i>DCC</i>) genes influence the structure of the human mesolimbic reward system. We conducted a systematic analysis of the potential functional single nucleotide polymorphisms (SNPs) in these genes associated with heroin addiction. We scanned the functional regions of these genes and identified 20 SNPs for genotyping by using the SNaPshot method. A total of 1080 samples, comprising 523 cases and 557 controls, were analyzed. We observed that <i>DCC</i> rs16956878, rs12607853, and rs2292043 were associated with heroin addiction. The T alleles of rs16956878 (<i>p</i> = 0.0004) and rs12607853 (<i>p</i> = 0.002) were significantly enriched in the case group compared with the controls. A lower incidence of the C allele of rs2292043 (<i>p</i> = 0.002) was observed in the case group. In block 2 of DCC (rs2292043-rs12607853-rs16956878), the frequency of the T-T-T haplotype was significantly higher in the case group than in the control group (<i>p</i> = 0.024), and fewer C-C-C haplotypes (<i>p</i> = 0.006) were detected in the case group. <i>DCC</i> may be an important candidate gene in heroin addiction, and rs16956878, rs12607853, and rs2292043 may be risk factors, thereby providing a basis for further genetic and biological research.</p></div

Demographic and addiction characteristics of <i>DCC</i> SNP rs16956878.

<p>Demographic and addiction characteristics of <i>DCC</i> SNP rs16956878.</p