A novel anti-virulence gene revealed by proteomic analysis in Shigella flexneri 2a

<p>Abstract</p> <p>Background</p> <p><it>Shigella flexneri </it>is a gram-negative, facultative pathogen that causes the majority of communicable bacterial dysenteries in developing countries. The virulence factors of <it>S. flexneri </it>have been shown to be produced at 37 degrees C but not at 30 degrees C. To discover potential, novel virulence-related proteins of <it>S. flexneri</it>, we performed differential in-gel electrophoresis (DIGE) analysis to measure changes in the expression profile that are induced by a temperature increase.</p> <p>Results</p> <p>The ArgT protein was dramatically down-regulated at 37 degrees C. In contrast, the ArgT from the non-pathogenic <it>E. coli </it>did not show this differential expression as in <it>S. flexneri</it>, which suggested that <it>argT </it>might be a potential anti-virulence gene. Competitive invasion assays in HeLa cells and in BALB/c mice with <it>argT </it>mutants were performed, and the results indicated that the over-expression of ArgT_Y225Dwould attenuate the virulence of <it>S. flexneri</it>. A comparative proteomic analysis was subsequently performed to investigate the effects of ArgT in <it>S. flexneri </it>at the molecular level. We show that HtrA is differentially expressed among different derivative strains.</p> <p>Conclusion</p> <p>Gene <it>argT </it>is a novel anti-virulence gene that may interfere with the virulence of <it>S. flexneri </it>via the transport of specific amino acids or by affecting the expression of the virulence factor, HtrA.</p

Effect of Cu addition on sedimentary bacterial community structure and heavy metal resistance gene abundance in mangrove wetlands

IntroductionMangroves are a unique ecosystem, but are often affected by heavy metal pollution. Bacterial communities in mangrove sediments usually respond to heavy-metal pollution stress by expressing specific heavy-metal resistance genes (HMRGs).MethodsMultivariate statistics were performed on Metagenomics as well as environmental data to evaluated the effects of Cu addition on the sedimentary bacterial community structure.Results and discussionUsing metagenomics technology, we found that the Shannon andChao1 indices of natural sediments were significantly higher than in sediments with artificially added Cu. Addition of Cu significantly altered bacterial community structure and diversity at the phylum, class and order levels in sediments. The relative abundance of HMRGs in Cuadded sediments was lower than that in natural sediments. Environmental factors that affect bacterial communities also affect HMRGs. However, the contribution of heavy-metal pollution to the change in HMRG abundance was much lower than its contribution to the change in the bacterial community, indicating that the relationship between HMRG abundance and heavy-metal pollution is complex and needs to be comprehensively studied

Elevated Aspartate and Alanine Aminotransferase Levels and Natural Death among Patients with Methamphetamine Dependence

Background: Methamphetamine is one of the fastest growing illicit drugs worldwide, causing multiple organ damage and excessive natural deaths. The authors aimed to identify potential laboratory indices and clinical characteristics associated with natural death through a two-phase study. Methods: Methamphetamine-dependent patients (n = 1,254) admitted to a psychiatric center in Taiwan between 1990 and 2007 were linked with a national mortality database for causes of death. Forty-eight subjects died of natural causes, and were defined as the case subjects. A time-efficient sex-and age-matched nested case-control study derived from the cohort was conducted first to explore the potential factors associated with natural death through a time-consuming standardized review of medical records. Then the identified potential factors were evaluated in the whole cohort to validate the findings. Results: In phase I, several potential factors associated with natural death were identified, including aspartate aminotransferase (AST), alanine aminotransferase (ALT), comorbid alcohol use disorder, and the prescription of antipsychotic drugs. In phase II, these factors were confirmed in the whole cohort using survival analysis. For the characteristics at the latest hospital admission, Cox proportional hazards models showed that the adjusted hazard ratios for natural death were 6.75 (p&lt;0.001) in the group with markedly elevated AST (&gt;80 U/L) and 2.66 (p&lt;0.05) in the group with mildly elevated AST (40-80 U/L), with reference to the control group (&gt;40 U/L). As for ALT, the adjusted hazard ratios were 5.41 (p&lt;0.001), and 1.44 (p&gt;0.05). Comorbid alcohol use disorder was associated with an increased risk of natural death, whereas administration of antipsychotic drugs was not associated with lowered risk. Conclusions: This study highlights the necessity of intensive follow-up for those with elevated AST and ALT levels and comorbid alcohol use disorder for preventing excessive natural deaths

Overview to the Hard X-ray Modulation Telescope (Insight-HXMT) Satellite

As China's first X-ray astronomical satellite, the Hard X-ray Modulation Telescope (HXMT), which was dubbed as Insight-HXMT after the launch on June 15, 2017, is a wide-band (1-250 keV) slat-collimator-based X-ray astronomy satellite with the capability of all-sky monitoring in 0.2-3 MeV. It was designed to perform pointing, scanning and gamma-ray burst (GRB) observations and, based on the Direct Demodulation Method (DDM), the image of the scanned sky region can be reconstructed. Here we give an overview of the mission and its progresses, including payload, core sciences, ground calibration/facility, ground segment, data archive, software, in-orbit performance, calibration, background model, observations and some preliminary results.Comment: 29 pages, 40 figures, 6 tables, to appear in Sci. China-Phys. Mech. Astron. arXiv admin note: text overlap with arXiv:1910.0443

SLXL1, a novel acrosomal protein, interacts with DKKL1 and is involved in fertilization in mice

BACKGROUND: Spermatogenesis is a complex cellular developmental process which involves diverse families of genes. The Xlr (X-linked, lymphocyte regulated) family includes multiple members, only a few of which have reported functions in meiosis, post-meiotic maturation, and fertilization of germ cells. Slx-like1 (Slxl1) is a member of the Xlr family, whose expression and function in spermatogenesis need to be elucidated. METHODOLOGY/PRINCIPAL FINDINGS: The mRNA and protein expression and localization of Slxl1 were investigated by RT-PCR, Western blotting and immunohistochemistry in different tissues and at different stages of spermatogenesis. The interacting partner of SLXL1 was examined by co-immunoprecipitation and co-localization. Assessment of the role of SLXL1 in capacitation, acrosome reaction, zona pellucida binding/penetration, and fertilization was carried out in vitro using blocking antisera. The results showed that Slxl1 mRNA and protein were specifically expressed in the testis. SLXL1 was exclusively located in the acrosome of post-meiotic germ cells and interacts with DKKL1 (Dickkopf-like1), which is an acrosome-associated protein and plays an important role in fertilization. The rates of zona pellucida binding/penetration and fertilization were significantly reduced by the anti-SLXL1 polyclonal antiserum. CONCLUSIONS/SIGNIFICANCE: SLXL1 is the first identified member of the XLR family that is associated with acrosome and is involved in zona pellucid binding/penetration and subsequent fertilization. These results, together with previous studies, suggest that Xlr family members participate in diverse processes from meiosis to fertilization during spermatogenesis

Large expert-curated database for benchmarking document similarity detection in biomedical literature search

Document recommendation systems for locating relevant literature have mostly relied on methods developed a decade ago. This is largely due to the lack of a large offline gold-standard benchmark of relevant documents that cover a variety of research fields such that newly developed literature search techniques can be compared, improved and translated into practice. To overcome this bottleneck, we have established the RElevant LIterature SearcH consortium consisting of more than 1500 scientists from 84 countries, who have collectively annotated the relevance of over 180 000 PubMed-listed articles with regard to their respective seed (input) article/s. The majority of annotations were contributed by highly experienced, original authors of the seed articles. The collected data cover 76% of all unique PubMed Medical Subject Headings descriptors. No systematic biases were observed across different experience levels, research fields or time spent on annotations. More importantly, annotations of the same document pairs contributed by different scientists were highly concordant. We further show that the three representative baseline methods used to generate recommended articles for evaluation (Okapi Best Matching 25, Term Frequency-Inverse Document Frequency and PubMed Related Articles) had similar overall performances. Additionally, we found that these methods each tend to produce distinct collections of recommended articles, suggesting that a hybrid method may be required to completely capture all relevant articles. The established database server located at https://relishdb.ict.griffith.edu.au is freely available for the downloading of annotation data and the blind testing of new methods. We expect that this benchmark will be useful for stimulating the development of new powerful techniques for title and title/abstract-based search engines for relevant articles in biomedical research.Peer reviewe