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In April 2019, 15 (10♂, 5♀) Kerivoula bats were collected by harp traps from Xishuangbanna, Yunnan Province, China. External and craniodental examination, multivariate statistical analyses and molecular phylogenetic inference (CoI, Cytb and Rag2 gene markers) indicated they are Kerivoula kachinensis and Kerivoula titania, respectively. Former represents a new chiropteran record from China, while the latter is a valid occurrence of K. titania in this region because recent study indicate a misidentification of “K. titania” in Guangdong, Guangxi and Hainan, China. All specimens are presently preserved at Key Laboratory of Conservation and Application in Biodiversity of South China in Guangzhou University, Guangzhou, China. Nowadays, four woolly bats occur in China including, Kerivoula furva, K. kachinensis, Kerivoula picta and K. titania, whilst there is a risk of underestimation the actual species diversity in China region when comparing those of neighboring region such as Vietnam. Supports for field survey need to be continued in future.

Disparities in the data that underlies clinical genomic interpretation is an acknowledged problem but there is a paucity of data demonstrating it. The National Institutes of Health’sAll of UsResearch Program aims to collect whole genome sequences, electronic health record (EHR) data, surveys and physical measurements for over a million participants of diverse ancestry and varied access to healthcare resources. We grouped participants by computed genetic ancestry and summarized the frequency of pathogenic variation within these groups. The European subgroup showed the highest rate of pathogenic variation (2.1%), with other ancestry groups ranging from 1.04% (East Asian) to 1.87% (‘Other’). Pathogenic variants were most frequently observed in genes related to Breast/Ovarian Cancer, Hypercholesterolemia or Hemochromatosis. Variant frequencies were consistent with gnomAD and some notable exceptions were resolved using gnomAD subsets. We additionally use this data to enrich sets of participants for specific genetic findings and to calculate penetrance. Differences in the frequency of pathogenic variants observed between ancestral groups generally indicate biases of ascertainment, but some may indicate differences in disease prevalence. These analyses are available on theAll of UsResearcher Workbench.

Actually, only two pangolin species occur naturally in China, namely the Chinese pangolin (Manis pentadactyla) and the Sunda pangolin (Manis javanica). The Sunda pangolin was found to occur naturally in Yunnan, China, but only with a narrow distribution in the Xishuangbanna and Pu'er City. The Indian pangolin (Manis crassicaudata) did not occur in China. The previous claim that this species is naturally distributed in China was found to originate from a mistake in the book "The Mammals of China and Mongolia" written by Allen in 1938.

Genomic medicine holds great promise for improving health care, but integrating searchable and actionable genetic data into electronic health records (EHRs) remains a challenge. Here we describe Neptune, a system for managing the interaction between a clinical laboratory and an EHR system during the clinical reporting process. We developed Neptune and applied it to two clinical sequencing projects that required report customization, variant reanalysis, and EHR integration. Neptune has been applied for the generation and delivery of over 15,000 clinical genomic reports. This work spans two clinical tests based on targeted gene panels that contain 68 and 153 genes respectively. These projects demanded customizable clinical reports that contained a variety of genetic data types including single-nucleotide variants (SNVs), copy-number variants (CNVs), pharmacogenomics, and polygenic risk scores. Two variant reanalysis activities were also supported, highlighting this important workflow. Methods are needed for delivering structured genetic data to EHRs. This need extends beyond developing data formats to providing infrastructure that manages the reporting process itself. Neptune was successfully applied on two high-throughput clinical sequencing projects to build and deliver clinical reports to EHR systems. The software is open source and available at https://gitlab.com/bcm-hgsc/neptune .

A new species of the genus Gonyosoma Wagler is described from Yunnan Province, China. The new species closely resembles G. prasinum (Blyth), but it is differentiated from the latter species by the following characters: precloacal plate divided, iris blue and inside of mouth greyish-white in life. Based on phylogenetic analyses of mitochondrial cytochrome b sequence data, the new species is recovered as the sister species to G. prasinum by Bayesian Inference and Maximum Likelihood analyses. The uncorrected pairwise distance between the new species and other species of the genus Gonyosoma ranged from 11.78% to 17.07% calculated using the mitochondrial cytochrome b sequence. This discovery increases the number of Gonyosoma species to seven.

Background Pressure ulcer (PU) is a common complication of acute and long-time hospitalization, especially in elderly patients. The incidence and prevalence of PU are swiftly fortifying. Currently, our purpose was to investigate the functional impacts of circ-Ttc3 on PU. Methods HaCaT cells were pretreated under hypoxia condition. Cell counting kit 8 assay and flow cytometry were utilized to test HaCaT cell viability and apoptosis. Quantitative reverse transcription polymerase chain reaction was utilized to determine circ-Ttc3 and miR-449a expression. Western blot was performed to examine apoptosis-associated proteins expression. Subsequently, the above-described investigations were reperformed after miR-449a upregulation. Results Hypoxia induced apoptosis and declined viability in HaCaT cells. Circ-Ttc3 expression was enhanced after transfection with circ-Ttc3 expressing vector. Overexpressing circ-Ttc3 raised viability and reduced apoptosis in HaCaT cells. Moreover, miR-449a expression was elevated by hypoxia and reversed by overexpressing circ-Ttc3. And circ-Ttc3 exerted its effect via downregulating miR-449a. Finally, overexpressing circ-Ttc3 activated nuclear factor kappa-B (NF-κB) and phosphatidylinositol 3 kinase (PI3K)/protein kinase B (AKT) pathways via downregulating miR-449a. Conclusion Our data suggested that circ-Ttc3 alleviated hypoxic injury and activated NF-κB and PI3K/AKT pathways by downregulating miR-449a in HaCaT cells.

PURPOSE: The Mayo-Baylor RIGHT 10K Study enabled preemptive, sequence-based pharmacogenomics (PGx)-driven drug prescribing practices in routine clinical care within a large cohort. We also generated the tools and resources necessary for clinical PGx implementation and identified challenges to be overcome. Furthermore, we measured the frequency of both common genetic variation for which clinical guidelines already exist and that of rare variation that could be detected by DNA sequencing, rather than genotyping. METHODS: Targeted oligonucleotide-capture sequencing of 77 “pharmacogenes” was performed using DNA from 10,077 consented Mayo Clinic Biobank volunteers. The resulting predicted drug response related phenotypes for 13 genes, including CYP2D6 and HLA, affecting 21 drug-gene pairs, were deposited preemptively in the Mayo electronic health record (EHR). RESULTS: For the 13 pharmacogenes of interest, the genomes of 79% of participants carried clinically actionable variants in 3 or more genes and DNA sequencing identified an average of 3.3 additional conservatively predicted deleterious variants that would not have been evident using genotyping. CONCLUSIONS: Implementation of preemptive rather than reactive, sequence-based rather than genotype-based PGx prescribing revealed nearly universal patient applicability and required integrated institution-wide resources to fully realize individualized drug therapy and to demonstrate more efficient use of health care resources.

Hailstorms has been reported to cause mortality of mammals or birds around the world, but the effect of hailstorms on tropical avian species has seldomly been documented. In April 2020, a hailstorm hit Xishuangbanna in south China and was reported to kill 45 Asian Openbills. We estimated the effect of hail by doing fieldwork and interviews. We walked along transects to survey the local avian diversity 3 days after the hail; checked the dead species along the transect; and also interviewed 67 local villagers in 14 villages in the impacted area. We found no evidence that other species were killed by the hail and recorded 40 bird species along the transects in April. Four months later, we surveyed the same transects and recorded 38 species, and the Asian Openbill stayed as one of the most dominant bird species. We concluded that the Asian Openbill is more vulnerable to hail compared with other local birds, but this single hail event did not have an obvious long-term impact on the population. The result provided an important case study for a tropical bird's response to extreme climate events and we suggested more similar observations to be made in the future.

Bedsore is a familiar disease, which fearfully harms the health of the patients. We investigated the efficacy and mechanism of circular RNA circANKRD36 on HaCaT cell in inflammatory damage. CCK-8 and flow cytometry were respectively used to investigate the efficacies of lipopolysaccharide (LPS), circANKRD36, and microRNA (miR)-15 on cell viability and apoptosis. Moreover, circANKRD36 and miR-15 expression were changed by cell transfection and investigated by reverse transcription-quantitative polymerase chain reaction. Furthermore, the levels of Bax, pro caspase-3, cleaved caspase-3, interleukin (IL)-1β, IL-6, and proteins of the pathway were investigated by Western blot. Otherwise, the levels of IL-1β and IL-6 were investigated by enzyme-linked immunosorbent assay. Reactive oxygen species (ROS) was investigated by ROS assay. The relation between myeloid differentiation factor 88 (MyD88) and miR-15 was investigated by luciferase assay. LPS caused inflammatory damage and upregulated circANKRD36. circANKRD36 was silenced in cells and si-circANKRD36 remitted inflammatory damage. Furthermore, si-circANKRD36 negatively regulated miR-15 and miR-15 inhibitor could reverse the efficacies of si-circANKRD36. Besides, si-circANKRD36 restrained the NF-κB pathway by upregulating miR-15. Finally, MyD88 was authenticated as a target of miR-15. circANKRD36 remitted cell inflammatory damage upregulating miR-15/MyD88 via the NF-κB pathway in HaCaT cells.

Background Chronic pain is frequently comorbid with depression in clinical practice. Recently, alterations in gut microbiota and metabolites derived therefrom have been found to potentially contribute to abnormal behaviors and cognitive dysfunction via the “microbiota–gut–brain” axis. Methods PubMed was searched and we selected relevant studies before October 1, 2019. The search keyword string included “pain OR chronic pain” AND “gut microbiota OR metabolites”; “depression OR depressive disorder” AND “gut microbiota OR metabolites”. We also searched the reference lists of key articles manually. Results This review systematically summarized the recent evidence of gut microbiota and metabolites in chronic pain and depression in animal and human studies. The results showed the pathogenesis and therapeutics of chronic pain and depression might be partially due to gut microbiota dysbiosis. Importantly, bacteria-derived metabolites, including short-chain fatty acids, tryptophan-derived metabolites, and secondary bile acids, offer new insights into the potential linkage between key triggers in gut microbiota and potential mechanisms of depression. Conclusion Studying gut microbiota and its metabolites has contributed to the understanding of comorbidity of chronic pain and depression. Consequently, modulating dietary structures or supplementation of specific bacteria may be an available strategy for treating chronic pain and depression.

The advancement of precision medicine requires new methods to coordinate and deliver genetic data from heterogeneous sources to physicians and patients. The eMERGE III Network enrolled >25,000 participants from biobank and prospective cohorts of predominantly healthy individuals for clinical genetic testing to determine clinically actionable findings. The network developed protocols linking together the 11 participant collection sites and 2 clinical genetic testing laboratories. DNA capture panels targeting 109 genes were used for testing of DNA and sample collection, data generation, interpretation, reporting, delivery, and storage were each harmonized. A compliant and secure network enabled ongoing review and reconciliation of clinical interpretations, while maintaining communication and data sharing between clinicians and investigators. A total of 202 individuals had positive diagnostic findings relevant to the indication for testing and 1,294 had additional/secondary findings of medical significance deemed to be returnable, establishing data return rates for other testing endeavors. This study accomplished integration of structured genomic results into multiple electronic health record (EHR) systems, setting the stage for clinical decision support to enable genomic medicine. Further, the established processes enable different sequencing sites to harmonize technical and interpretive aspects of sequencing tests, a critical achievement toward global standardization of genomic testing. The eMERGE protocols and tools are available for widespread dissemination.

Long noncoding RNAs (lncRNAs) play important roles in carcinogenesis. It is necessary to uncover the detailed pattern of comprehensive lncRNA expression in the genome during the development of gastric cancer (GC). We implemented lncRNA microarray analysis in 5 paired GC tissues to detect the lncRNA expression profile. Moreover, we set out to explore the biological function, clinical application and molecular basis of the aberrant lncRNA in GC. In addition, we used the high-throughput microarray to identify the target gene of the aberrant lncRNA. We found that FLJ22763, a novel lncRNA, had significantly lower expression in GC tissues. Decreased expression of FLJ22763 was positively correlated with a lower-level histological grade and the depth of invasion. The ectopic expression of lncRNA FLJ22763 significantly suppressed the biological malignant behavior of GC cells and inhibited xenograft tumor growth (both P 0.001). Notably, FLJ22763 displayed a considerable predictive effect in the prognosis of GC (log-rank, P = 0.003). Furthermore, we found that FLJ22763 was negatively associated with ACLY, regulating the mRNA and protein levels of ACLY. Our findings suggested that FLJ22763 may act as a suppressor gene to regulate the expression of ACLY, and its down-expression may be an independent prognostic factor in patients with GC.

A high temperature damage model was presented to investigate the flexural behavior and flaw sensitivity of ZrB2-SiC-graphite composite at high temperatures. This high temperature damage model combined an asymmetry between tension and compression, and effects of temperature and mechanical load. Room temperature tensile modulus, compressive modulus and fracture loads at different temperatures were measured by experimental tests. Experimental results show that tensile modulus is 1.2 times for compressive modulus in the direction parallel to graphite flake. Moreover, the fracture load of ZrB2-SiC-graphite composite measured by three-point bending method has obvious temperature dependence. These above experimental results were applied to simulate the high temperature flexural behavior. Numerical results declare that the temperature has great effect on the fracture strength and mechanical damage of ZrB2-SiC-graphite composite. With the increase of temperature, the maximum stress and mechanical damage exhibit less sensitive to the crack length above the brittle-ductile transition temperature (1300 °C).

In this paper, a prefabricated wood-plastic enclosure finite element analysis model, and its stress distribution under wind load and the failure mode of the enclosure under the maximum wind load bearing capacity are analyzed with the ABAQUS finite element code. The results show that under the horizontally distributed load, the mid-span deflection, mid-span stress and strain of the baffle gradually increase from bottom to top. The column has greater constraints on the baffles 1-1 to 1-3, and less on the upper baffle, resulting in a gradual increase in the maximum stress of the upper baffle. When the horizontally distribution load reached the maximum load of 1.74 KPa, cracks began to appear at the support contacts of the columns, resulting in component failure.

Figure S1-S10 (Online). Table S1. The top 10 significantly upregulated and downregulated lncRNAs identified by Arraystar Human lncRNA/mRNA chip. Table S2. The prime sequences of target genes used in real-time PCR. (DOCX 1257Â kb)

Background Juvenile‐onset cataracts are known among the Hutterites of North America. Despite being identified over 30 years ago, this autosomal recessive condition has not been mapped, and the disease gene is unknown. Methods We performed whole exome sequencing of three Hutterite‐type cataract trios and follow‐up genotyping and mapping in four extended kindreds. Results Trio exomes enabled genome‐wide autozygosity mapping, which localized the disease gene to a 9.5‐Mb region on chromosome 6p. This region contained two candidate variants, LEMD2 c.T38G and MUC21 c.665delC. Extended pedigrees recruited for variant genotyping revealed multiple additional relatives with juvenile‐onset cataract, as well as six deceased relatives with both cataracts and sudden cardiac death. The candidate variants were genotyped in 84 family members, including 17 with cataracts; only the variant in LEMD2 cosegregated with cataracts (LOD = 9.62). SNP‐based fine mapping within the 9.5 Mb linked region supported this finding by refining the cataract locus to a 0.5‐ to 2.9‐Mb subregion (6p21.32‐p21.31) containing LEMD2 but not MUC21. LEMD2 is expressed in mouse and human lenses and encodes a LEM domain‐containing protein; the c.T38G missense mutation is predicted to mutate a highly conserved residue within this domain (p.Leu13Arg). Conclusion We performed a genetic and genomic study of Hutterite‐type cataract and found evidence for an association of this phenotype with sudden cardiac death. Using combined genetic and genomic approaches, we mapped cataracts to a small portion of chromosome 6 and propose that they result from a homozygous missense mutation in LEMD2.

Zinc (Zn) deficiency caused by inadequate dietary intake is a global nutritional problem, so increasing Zn concentrations in crops is a challenging and high-priority research task. A field experime...

// Mulong Du 1, * , Weizhi Wang 2, * , Hua Jin 3, * , Qiaoyan Wang 1 , Yuqiu Ge 1 , Jiafei Lu 1 , Gaoxiang Ma 1 , Haiyan Chu 1, 4 , Na Tong 1, 4 , Haixia Zhu 3 , Meilin Wang 1, 4 , Fulin Qiang 3 , Zhengdong Zhang 1, 4 1 Department of Environmental Genomics, Jiangsu Key Laboratory of Cancer Biomarkers, Prevention and Treatment, Cancer Center, Nanjing Medical University, Nanjing, China 2 Department of General Surgery, the First Affiliated Hospital of Nanjing Medical University, Nanjing, China 3 Core Laboratory, Nantong Tumor Hospital, Nantong, China 4 Department of Genetic Toxicology, the Key Laboratory of Modern Toxicology of Ministry of Education, School of Public Health, Nanjing Medical University, Nanjing, China * These authors have contributed equally to this work Correspondence to: Zhengdong Zhang, e-mail: drzdzhang@gmail.com Keywords: long noncoding RNA, HOTAIR, genetic variants, gastric cancer Received: May 12, 2015 Accepted: August 24, 2015 Published: September 04, 2015 ABSTRACT The HOX transcript antisense intergenic RNA ( HOTAIR ), a well-known long noncoding RNA, is involved in pathogenesis and progress of multiple tumors. Its ectopic expression and biological functions have been observed in gastric cancer. In this study, we conducted a two-stage case-control study to evaluate whether genetic variations of HOTAIR were associated with gastric cancer risk. We identified that a single nucleotide polymorphism (SNP) rs4759314 was significantly associated with the increased gastric cancer risk with an odds ratio (OR) of 1.39 [95% confidence interval (CI) = 1.13–1.71, P = 0.002] in the combined sets. Further functional experiments revealed the allele-specific effects on HOTAIR and HOXC11 expressions in gastric cancer tissues, of which HOTAIR and HOXC11 expressions of individuals carrying with AG genotype were much higher than those with AA genotype; similarly, the effects occurred in intronic promoter activities, of which the promoter activity of G allele was more pronounced than that of A allele. Interestingly, we identified a novel potential oncogene HOXC11 in gastric cancer pathogenesis with differential expression in gastric cancer tissues by association analysis with candidate gene strategy. These results suggest that SNP rs4759314 of HOTAIR acts as a potential biomarker for predicting gastric cancer, and the role of HOXC11 in gastric cancer etiology is warranted to further investigation.

Background Emerging evidence has shown that dysregulation function of long non-coding RNAs (lncRNAs) implicated in gastric cancer (GC). However, the role of the differentially expressed lncRNAs in GC has not fully explained. Methods LncRNA expression profiles were determined by lncRNA microarray in five pairs of normal and GC tissues, further validated in another 75 paired tissues by quantitative real-time PCR (qRT-PCR). Overexpression of lncRNA MT1JP was conducted to assess the effect of MT1JP in vitro and in vivo. The biological functions were demonstrated by luciferase reporter assay, western blotting and rescue experiments. Results LncRNA MT1JP was significantly lower in GC tissues than adjacent normal tissues, and higher MT1JP was remarkably related to lymph node metastasis and advance stage. Besides, GC patients with higher MT1JP expression had a well survival. Functionally, overexpression of lncRNA MT1JP inhibited cell proliferation, migration, invasion and promoted cell apoptosis in vitro, and inhibited tumor growth and metastasis in vivo. Functional analysis showed that lncRNA MT1JP regulated FBXW7 expression by competitively binding to miR-92a-3p. MiR-92a-3p and down-regulated FBXW7 reversed cell phenotypes caused by lncRNA MT1JP by rescue analysis. Conclusion MT1JP, a down-regulated lncRNA in GC, was associated with malignant tumor phenotypes and survival of GC. MT1JP regulated the progression of GC by functioning as a competing endogenous RNA (ceRNA) to competitively bind to miR-92a-3p and regulate FBXW7 expression. Our study provided new insight into the post-transcriptional regulation mechanism of lncRNA MT1JP, and suggested that MT1JP may act as a potential therapeutic target and prognosis biomarker for GC. Electronic supplementary material The online version of this article (10.1186/s12943-018-0829-6) contains supplementary material, which is available to authorized users.

Current procedures for diagnosis and biomarker examination of colorectal cancer (CRC) are invasive and unpleasant. There is a great need to identify sensitive and specific biomarkers for early diagnosis of CRC. Circulating microRNAs (miRNAs) are promising molecular markers for CRC prediction. We performed a comprehensive meta-analysis to integrate an evaluation index for diagnostic accuracy of circulating miRNAs in diagnosing CRC patients. Furthermore, we conducted an independent validation set of 49 CRC patients and 49 healthy controls. In our meta-analysis, we found that miR-21 yielded a pooled area under ROC curve (AUC) of 0.867 (sensitivity: 76%, specificity: 82%) in discriminating CRC from controls, and miR-92a yielded a summary AUC of 0.803 (sensitivity: 77%, specificity: 68%); miR-21 had a higher diagnostic efficiency than miR-92a. In the further validation, plasma miR-21 levels in CRC patients were significantly higher than levels observed in healthy subjects. A ROC curve analysis showed a consistent result. However, this phenotype was not present in miR-92a. Moreover, the expression trend of miR-21 in plasma samples was in line with that of tissue samples, along with the cellular level. Current evidences suggest that plasma miR-21 could be a reliable and non-invasive biomarker for CRC diagnosis. Studies with larger cohorts that include the diagnostic value of plasma miR-21 for CRC are warranted.

The human X and Y chromosomes evolved from an ordinary pair of autosomes, but millions of years ago genetic decay ravaged the Y chromosome, and only three per cent of its ancestral genes survived. We reconstructed the evolution of the Y chromosome across eight mammals to identify biases in gene content and the selective pressures that preserved the surviving ancestral genes. Our findings indicate that survival was nonrandom, and in two cases, convergent across placental and marsupial mammals. We conclude that the gene content of the Y chromosome became specialized through selection to maintain the ancestral dosage of homologous X-Y gene pairs that function as broadly expressed regulators of transcription, translation and protein stability. We propose that beyond its roles in testis determination and spermatogenesis, the Y chromosome is essential for male viability, and has unappreciated roles in Turner's syndrome and in phenotypic differences between the sexes in health and disease.

Prostate cancer (PCa) gene expression marker 1 (PCGEM1), a long noncoding RNA, has drawn increasing attention for its important role in PCa. However, the association between genetic variations in the PCGEM1 gene and risk of PCa has not been investigated yet. We investigated the effect of two tagging single-nucleotide polymorphism (tSNPs; rs6434568 and rs16834898) in PCGEM1 gene on PCa risk in the Chinese men. Odds ratios (ORs) with 95% confidence intervals (CIs) were used to assess the association. We found a significantly decreased risk of PCa for rs6434568 AC and AC/AA genotype (adjusted OR=0.76, 95% CI=0.60–0.97 for AC; adjusted OR=0.76, 95% CI=0.61–0.96 for AC/AA), as well as rs16834898 AC and AC/CC genotype (adjusted OR=0.76, 95% CI=0.59–0.97 for AC; adjusted OR=0.79, 95% CI=0.62–0.99 for AC/CC), compared with the CC and AA genotypes, respectively. When we evaluated these two tSNPs together based on the risk alleles (that is, rs6434568 C and rs16834898 A), we found that the combined genotypes with four risk alleles were associated with an increased risk of PCa compared with those carrying 0–3 risk alleles (1.53, 1.19–1.97), and this increased risk was more pronounced among subjects of⩽70 years (1.80, 1.24–2.62), Gleason score⩽7 (1.68, 1.28–2.22) and PSA level⩾20 (1.64, 1.24–2.18). Our results indicated that PCGEM1 polymorphisms may contribute to PCa risk in Chinese men. Additional functional analyses are required to detect the detailed mechanism underlying the observed association.

This evolutionary decay was driven by a series of five ‘stratification’ events. Each event suppressed X–Y crossing over within a chromosome segment or ‘stratum’, incorporated that segment into the MSY and subjected its genes to the erosive forces that attend the absence of crossing over 2,6 . The last of these events occurred 30 million years ago, 5 million years before the human and Old World monkey lineages diverged. Although speculation abounds regarding ongoing decay and looming extinction of the human Y chromosome 7–10 , remarkably little is known about how many MSY genes were lost in the human lineage in the 25 million years that have followed its separation from the Old World monkey lineage. To investigate this question, we sequenced the MSY of the rhesus macaque, an Old World monkey, and compared it to the human MSY. We discovered that during the last 25 million years MSY gene loss in the human lineage was limited to the youngest stratum (stratum 5), which comprises three percent of the human MSY. In the older strata, which collectively comprise the bulk of the human MSY, gene loss evidently ceased more than 25 million years ago. Likewise, the rhesus MSY has not lost any older genes (from strata 1–4) during the past 25 million years, despite its major structural differences to the human MSY. The rhesus MSY is simpler, with few amplified gene families or palindromes that might enable intrachromosomal recombination and repair. We present an empirical reconstruction of human MSY evolution in which each stratum transitioned from rapid, exponential loss of ancestral genes to strict conservation through purifying selection. The human Y chromosome no longer engages in crossing over with its once-identical partner, the X chromosome, except in its pseudoautosomal regions. During evolution, X–Y crossing over was suppressed in five different chromosomal regions at five different times, each probably resulting from an inversion in the Y chromosome 2,3 . Each of these regions of the Y chromosome then began its own individual course of degeneration, experiencing deletions and gene loss. Comparison of the present-day X and Y chromosomes enables identification of these five evolutionary ‘strata’ in the MSY (and X chromosome); their distinctive degrees of X–Y differentiation indicate their evolutionary ages 2,3 . The oldest stratum (stratum 1) dates back over 240 million years (Myr) 2 and is the most highly differentiated, and the youngest stratum (stratum 5) originated only 30 Myr ago and displays the highest X–Y nucleotide sequence similarity within the MSY 3 . The five strata and their respective decay processes, over tens to hundreds of millions of years of mammalian evolution, offer replicate experiments of nature from which to reconstruct the trajectories and kinetics of gene loss in the MSY. Only the human and chimpanzee MSYs had been sequenced before the present study, and they are separated by just 6 Myr of evolution. We decided to examine the MSY of a much more distant relative, the rhesus macaque (Macaca mulatta), to enable us to reconstruct gene loss and conservation in the MSY during the past 25 Myr. We sequenced the rhesus MSY using bacterial artificial chromosome (BAC) clones and the SHIMS (single-haplotype iterative mapping and sequencing) strategy that has previously been used in the human and chimpanzee MSYs 4,11–13 as well as in the chicken Z chromosome 5 . The resulting sequence is comprised of 11.0 megabases (Mb), is complete aside from three small gaps and has an error rate of about one nucleotide per Mb. We ordered and oriented the finished sequence contigs by fluorescence in situ hybridization and radiation hybrid mapping (Supplementary Figs 1–6, Supplementary Table 1, Supplemen

The motion state of ion wind in discharge channel is analyzed for different discharge configurations by experimental method and numerical simulation, as well as analysis on electro-hydrodynamic theory. The conception of inception voltage of ion wind is proposed; the velocity of ion wind is obtained near the plate electrode and that near the wire as functions of the applied voltage. A model to simulate wire-plate discharge is established and the ion wind is simulated in discharge channel by this model through replacing the ion wind by the dynamic wind. Furthermore, the reason is given to explain the error between the simulated velocity and experimental one and that between simulated velocity and theoretical one. The simulated results also show that a double-helix structure distribution of ion wind exists in the discharge channel. The results provide a necessary theoretical support for the research on the interactions between different kinds of materials in discharge channel.

Udgivelsesdato: 2006-Apr-27 After the completion of a draft human genome sequence, the International Human Genome Sequencing Consortium has proceeded to finish and annotate each of the 24 chromosomes comprising the human genome. Here we describe the sequencing and analysis of human chromosome 3, one of the largest human chromosomes. Chromosome 3 comprises just four contigs, one of which currently represents the longest unbroken stretch of finished DNA sequence known so far. The chromosome is remarkable in having the lowest rate of segmental duplication in the genome. It also includes a chemokine receptor gene cluster as well as numerous loci involved in multiple human cancers such as the gene encoding FHIT, which contains the most common constitutive fragile site in the genome, FRA3B. Using genomic sequence from chimpanzee and rhesus macaque, we were able to characterize the breakpoints defining a large pericentric inversion that occurred some time after the split of Homininae from Ponginae, and propose an evolutionary history of the inversion.

The human X chromosome has a unique biology that was shaped by its evolution as the sex chromosome shared by males and females. We have determined 99.3% of the euchromatic sequence of the X chromosome. Our analysis illustrates the autosomal origin of the mammalian sex chromosomes, the stepwise process that led to the progressive loss of recombination between X and Y, and the extent of subsequent degradation of the Y chromosome. LINE1 repeat elements cover one-third of the X chromosome, with a distribution that is consistent with their proposed role as way stations in the process of X-chromosome inactivation. We found 1,098 genes in the sequence, of which 99 encode proteins expressed in testis and in various tumour types. A disproportionately high number of mendelian diseases are documented for the X chromosome. Of this number, 168 have been explained by mutations in 113 X-linked genes, which in many cases were characterized with the aid of the DNA sequence.

Although some studies have assessed the prognostic value of HOTAIR in patients with digestive system tumors, the relationship between the HOTAIR and outcome of digestive system tumors remains unknown. The PubMed was searched to identify the eligible studies. Here, we performed a meta-analysis with 11 studies, including a total of 903 cases. Pooled hazard ratios (HRs) and 95 % confidence interval (CI) of HOTAIR for cancer survival were calculated. We found that the pooled HR elevated HOTAIR expression in tumor tissues was 2.36 (95 % CI 1.88–2.97) compared with patients with low HOTAIR expression. Moreover, subgroup analysis revealed that HOTAIR overexpression was also markedly associated with short survival for esophageal squamous cell carcinoma (HR 2.19, 95 % CI 1.62–2.94) and gastric cancer (HR 1.66, 95 % CI 1.02–2.68). In addition, up-regulated HOTAIR was significantly related to survival of digestive system cancer among the studies with more follow-up time (follow time ≥ 5 years) (HR 2.51, 95 % CI 1.99–3.17). When stratified by HR resource and number of patients, the result indicated consistent results with the overall analysis. Subgroup analysis on ethnicities did not change the prognostic influence of elevated HOTAIR expression. Additionally, we conducted an independent validation cohort including 71 gastric cancer cases, in which patients with up-regulated HOTAIR expression had an unfavorable outcome with HR of 2.10 (95 % CI 1.10–4.03). The results suggest that aberrant HOTAIR expression may serve as a candidate positive marker to predict the prognosis of patients with carcinoma of digestive system.

We describe the landscape of somatic genomic alterations of 66 chromophobe renal cell carcinomas (ChRCCs) based on multidimensional and comprehensive characterization, including mitochondrial DNA (mtDNA) and whole genome sequencing. The result is consistent that ChRCC originates from the distal nephron compared to other kidney cancers with more proximal origins. Combined mtDNA and gene expression analysis implicates changes in mitochondrial function as a component of the disease biology, while suggesting alternative roles for mtDNA mutations in cancers relying on oxidative phosphorylation. Genomic rearrangements lead to recurrent structural breakpoints within TERT promoter region, which correlates with highly elevated TERT expression and manifestation of kataegis, representing a mechanism of TERT up-regulation in cancer distinct from previously-observed amplifications and point mutations.

MicroRNAs (miRNAs) are a class of short non-coding, single-stranded RNAs, which perform posttranscriptional regulatory functions as tumor suppressors or oncogenes. Single nucleotide polymorphisms (SNPs) in microRNAs (miRNAs) genes are currently being identified for contributing to cancer risk, prognosis and survival. We investigated whether genetic variations of miRNAs were associated with the risk and prognosis of renal cell carcinoma (RCC). We genotyped four common miRNA SNPs (i.e. miR-146a rs2910164, miR-149 rs2292832, miR-196a2 rs11614913 and miR-499 rs3746444) to assess their associations with RCC risk in a two-stage case-control study (355 cases and 362 controls in discovery set, meanwhile 647 cases and 660 controls in validation set), as well as RCC survival in 311 patients. We found that the miR-196a2 SNP rs11614913 was associated with RCC susceptibility in recessive model [CC versus TT/TC, adjusted odds ratio = 0.65, 95% confidence interval (CI) = 0.52-0.83] and with survival of RCC in dominant model (TC/CC versus TT, adjusted hazard ratio = 0.40, 95% CI = 0.18-0.89). Meanwhile, the rs11614913 CC genotype was associated with the significantly decreased expression of miR-196a-5p in 26 renal cancer tissues (P = 0.018). Moreover, luciferase reporter assays revealed the potential effect of rs11614913 SNP on the binding of miR-196a-3p to its targets. These results suggested that the miR-196a2 rs11614913 may contribute to the genetic susceptibility and prognosis for RCC, which may act as a biomarker for RCC occurrence and prognosis.

We have sequenced a 1.1-Mb region of human chromosome 22q containing the dosage-sensitive gene(s) responsible for cat eye syndrome (CES) as well as the 450-kb homologous region on mouse chromosome 6. Fourteen putative genes were identified within or adjacent to the human CES critical region (CESCR), including three known genes (IL-17R,ATP6E, and BID) and nine novel genes, based on EST identity. Two putative genes (CECR3 and CECR9) were identified, in the absence of EST hits, by comparing segments of human and mouse genomic sequence around two solitary amplified exons, thus showing the utility of comparative genomic sequence analysis in identifying transcripts. Of the 14 genes, 10 were confirmed to be present in the mouse genomic sequence in the same order and orientation as in human. Absent from the mouse region of conserved synteny areCECR1, a promising CES candidate gene from the center of the contig, neighboring CECR4, and CECR7 andCECR8, which are located in the gene-poor proximal 400 kb of the contig. This latter proximal region, located ∼1 Mb from the centromere, shows abundant duplicated gene fragments typical of pericentromeric DNA. The margin of this region also delineates the boundary of conserved synteny between the CESCR and mouse chromosome 6. Because the proximal CESCR appears abundant in duplicated segments and, therefore, is likely to be gene poor, we consider the putative genes identified in the distal CESCR to represent the majority of candidate genes for involvement in CES.

Background and purpose Ketamine can completely eliminate pain associated with propofol injection. However, the effective dose of ketamine to eliminate propofol injection pain has not been determined. The purpose of this study was to determine the effective dose of ketamine needed to eliminate pain in 50% and 95% of patients (ED50 and ED95, respectively) during propofol injections. Methods This study was conducted in a double-blinded fashion and included 50 patients scheduled for elective gynecological laparoscopy under general anesthesia. The initial dose of ketamine used in the first patient was 0.25 mg/kg. The dosing modifications were in increments or decrements of 0.025 mg/kg. Ketamine was administered 15 seconds before injecting propofol (2.5 mg/kg), which was injected at a rate of 1 mL/s. Patients were asked to rate their pain during propofol injection every 5 seconds using a 0–3 pain scale. The highest pain score was recorded. The ED50, ED95 and 95% confidence intervals (CI) were determined by probit analyses. Results The dose of ketamine ranged from 0.175 to 0.275 mg/kg. The ED50 and ED95 of ketamine for eliminating pain during propofol injection were 0.227 mg/kg and 0.283 mg/kg, respectively (95%CI: 0.211–0.243 mg/kg and 0.26–0.364 mg/kg, respectively). Conclusion Ketamine at an approximate dose of 0.3 mg/kg was effective in eliminating pain during propofol injection.

Background Community acquired (CA) methicillin-resistant Staphylococcus aureus (MRSA) increasingly causes disease worldwide. USA300 has emerged as the predominant clone causing superficial and invasive infections in children and adults in the USA. Epidemiological studies suggest that USA300 is more virulent than other CA-MRSA. The genetic determinants that render virulence and dominance to USA300 remain unclear. Results We sequenced the genomes of two pediatric USA300 isolates: one CA-MRSA and one CA-methicillin susceptible (MSSA), isolated at Texas Children's Hospital in Houston. DNA sequencing was performed by Sanger dideoxy whole genome shotgun (WGS) and 454 Life Sciences pyrosequencing strategies. The sequence of the USA300 MRSA strain was rigorously annotated. In USA300-MRSA 2658 chromosomal open reading frames were predicted and 3.1 and 27 kilobase (kb) plasmids were identified. USA300-MSSA contained a 20 kb plasmid with some homology to the 27 kb plasmid found in USA300-MRSA. Two regions found in US300-MRSA were absent in USA300-MSSA. One of these carried the arginine deiminase operon that appears to have been acquired from S. epidermidis. The USA300 sequence was aligned with other sequenced S. aureus genomes and regions unique to USA300 MRSA were identified. Conclusion USA300-MRSA is highly similar to other MRSA strains based on whole genome alignments and gene content, indicating that the differences in pathogenesis are due to subtle changes rather than to large-scale acquisition of virulence factor genes. The USA300 Houston isolate differs from another sequenced USA300 strain isolate, derived from a patient in San Francisco, in plasmid content and a number of sequence polymorphisms. Such differences will provide new insights into the evolution of pathogens.

The draft genome sequence of Mannheimia haemolytica A1, the causative agent of bovine respiratory disease complex (BRDC), is presented. Strain ATCC BAA-410, isolated from the lung of a calf with BRDC, was the DNA source. The annotated genome includes 2,839 coding sequences, 1,966 of which were assigned a function and 436 of which are unique to M. haemolytica . Through genome annotation many features of interest were identified, including bacteriophages and genes related to virulence, natural competence, and transcriptional regulation. In addition to previously described virulence factors, M. haemolytica encodes adhesins, including the filamentous hemagglutinin FhaB and two trimeric autotransporter adhesins. Two dual-function immunoglobulin-protease/adhesins are also present, as is a third immunoglobulin protease. Genes related to iron acquisition and drug resistance were identified and are likely important for survival in the host and virulence. Analysis of the genome indicates that M. haemolytica is naturally competent, as genes for natural competence and DNA uptake signal sequences (USS) are present. Comparison of competence loci and USS in other species in the family Pasteurellaceae indicates that M. haemolytica , Actinobacillus pleuropneumoniae , and Haemophilus ducreyi form a lineage distinct from other Pasteurellaceae . This observation was supported by a phylogenetic analysis using sequences of predicted housekeeping genes.

Human chromosome 12 contains more than 1,400 coding genes and 487 loci that have been directly implicated in human disease. The q arm of chromosome 12 contains one of the largest blocks of linkage disequilibrium found in the human genome. Here we present the finished sequence of human chromosome 12, which has been finished to high quality and spans approximately 132 megabases, representing approximately 4.5% of the human genome. Alignment of the human chromosome 12 sequence across vertebrates reveals the origin of individual segments in chicken, and a unique history of rearrangement through rodent and primate lineages. The rate of base substitutions in recent evolutionary history shows an overall slowing in hominids compared with primates and rodents.

Nature 508, 494–499 (2014); doi:10.1038/nature13206 Jessica Alfoldi should have been listed with affiliation 1 in the author list. She performed BAC mapping, radiation hybrid mapping and real-time polymerase chain reaction analyses. The online versions of this Article have been corrected.

In order to seek a new control method which can control the dust, SO2, NOx and other pollutants comprehensively, a novel atomizing corona discharge device without external dynamic force was invented. The voltage-current (V-I) characteristics in different electrode structures were studied. In the cavity-wire type discharge structure, the voltage-current characteristics of de-ionized water, tap water and saturated solution of Ca(OH)2 were compared and analyzed. The results showed that: the atomizing effect of cavity-wire type discharge structure was better than that of cavity-plate under the same electrode diameter and voltage. A better atomizing effect could be obtained when the curvature radius of the cavity atomizing electrode was reduced. Active ions in solution had damaging effect on hydrogen bond among water molecules, which is in favour of solution atomization. This work will provide theoretical basis and experimental supports for a new field that the electrostatic and the wet flue gas desulphurization (WFGD) are combined together at the same time.

This paper focuses on the low collection efficiency of fine particles in air pollutant. Based on analyzing the collection rate of fine particles in electrostatic precipitator (ESP), a two-dimensional model of wire-plate discharge was established. The CFD code FLUENT was used to simulate the ionic winds at typical voltages 25, 40, and 45 kV, respectively. In the process of simulating, the ionic wind was replaced by the dynamic wind. According to the state graphs of ionic winds, the abnormal manifestation of the fine particles collection appeared in 40 kV voltage was explained. This work will provide a theoretical support for optimizing electrodes matching.