Molecular characterization, structural analysis and determination of host range of a novel bacteriophage LSB-1

<p>Abstract</p> <p>Background</p> <p>Bacteriophages (phages) are widespread in the environment and play a crucial role in the evolution of their bacterial hosts and the emergence of new pathogens.</p> <p>Results</p> <p>LSB-1, a reference coliphage strain, was classified as a member of the Podoviridae family with a cystic form (50 ± 5 nm diameter) and short tail (60 ± 5 nm long). The double stranded DNA was about 30 kilobase pairs in length. We identified its host range and determined the gp17 sequences and protein structure using shotgun analysis and bioinformatics technology.</p> <p>Conclusions</p> <p>Coliphage LSB-1 possesses a tailspike protein with endosialidase activity which is probably responsible for its specific enteroinvasive <it>E.coli </it>host range within the laboratory.</p

Molecular and Clinicopathologic Characterization of Intravenous Leiomyomatosis

Intravenous leiomyomatosis (IVL) is an unusual uterine smooth muscle proliferation that can be associated with aggressive clinical behavior despite a histologically benign appearance. It has some overlapping molecular characteristics with both uterine leiomyoma and leiomyosarcoma based on limited genetic data. In this study, we assessed the clinical and morphological characteristics of 28 IVL and their correlation with molecular features and protein expression, using array comparative genomic hybridization (aCGH) and Cyclin D1, p16, phosphorylated-Rb, SMARCB1, SOX10, CAIX, SDHB and FH immunohistochemistry. The most common morphologies were cellular (n=15), usual (n=11) and vascular (n=5; including 3 cellular IVL showing both vascular and cellular features). Among the immunohistochemical findings, the most striking was that all IVL showed differential expression of either p16 or Cyclin D1 in comparison to surrounding non-neoplastic tissue. Cytoplasmic phosphorylated-Rb was present in all but one IVL with hyalinization. SMARCB1, FH and SDHB were retained; S0X10 and CAIX were not expressed. The most common genetic alterations involved 1p (39%), 22q (36%), 2q (29%), 1q (25%), 13q (21%) and 14q (21%). Hierarchical clustering analysis of recurrent aberrations revealed 3 molecular groups: Group 1 (29%) and 2 (18%) with associated del(22q) and group 3 (18%) with del(10q). The remaining IVL had non-specific or no alterations by aCGH. Genomic index scores were calculated for all cases and showed no significant difference between the 14 IVL associated with aggressive clinical behavior (extrauterine extension or recurrence) and those without (median scores 5.15 vs 3.5). Among the 5 IVL associated with recurrence, 4 had a vascular morphology and 3 had alterations of 8q. Recurrent chromosome alterations detected herein overlap with those observed in the spectrum of uterine smooth muscle tumors and involve genes implicated in mesenchymal tumors at different sites with distinct morphological features

A new method of measuring optical turbulence of atmospheric surface layer at Antarctic Taishan Station with ultrasonic anemometer

To find the optimal location for large-aperture telescopes is a goal of astronomy. Chinese Antarctic astronomy has begun to flourish in recent years, and it is an urgent need in basic astronomical work to measure and analyze the optical turbulence spatiotemporal distribution in the Antarctic region. We analyzed turbulence data measured by a mobile atmospheric parameter measurement system from 30 December 2013 to 10 February 2014 at Antarctic Taishan Station. Because there is a discrepancy between the refractive index structure constant Cn2 measured by an ultrasonic anemometer with a single-point temperature structure function method and by micro-thermometer, a new method to measure Cn2 with a temperature spectrum method is proposed herein. Through comparing long-term continuous Cn2 data derived from ultrasonic anemometer with those via the new method and micro-thermometer, trend, magnitude and measured weak turbulence of ~2×10-16m 2/3 are generally satisfactory. The reason for the discrepancy in Cn2 measurement between the ultrasonic anemometer with the old method and micro-thermometer is investigated

Molecular characterization of a rice mutator-phenotype derived from an incompatible cross-pollination reveals transgenerational mobilization of multiple transposable elements and extensive epigenetic instability

BACKGROUND: Inter-specific hybridization occurs frequently in plants, which may induce genetic and epigenetic instabilities in the resultant hybrids, allopolyploids and introgressants. It remains unclear however whether pollination by alien pollens of an incompatible species may impose a "biological stress" even in the absence of genome-merger or genetic introgression, whereby genetic and/or epigenetic instability of the maternal recipient genome might be provoked. RESULTS: We report here the identification of a rice mutator-phenotype from a set of rice plants derived from a crossing experiment involving two remote and apparently incompatible species, Oryza sativa L. and Oenothera biennis L. The mutator-phenotype (named Tong211-LP) showed distinct alteration in several traits, with the most striking being substantially enlarged panicles. Expectably, gel-blotting by total genomic DNA of the pollen-donor showed no evidence for introgression. Characterization of Tong211-LP (S0) and its selfed progenies (S1) ruled out contamination (via seed or pollen) or polyploidy as a cause for its dramatic phenotypic changes, but revealed transgenerational mobilization of several previously characterized transposable elements (TEs), including a MITE (mPing), and three LTR retrotransposons (Osr7, Osr23 and Tos17). AFLP and MSAP fingerprinting revealed extensive, transgenerational alterations in cytosine methylation and to a less extent also genetic variation in Tong211-LP and its immediate progenies. mPing mobility was found to correlate with cytosine methylation alteration detected by MSAP but not with genetic variation detected by AFLP. Assay by q-RT-PCR of the steady-state transcript abundance of a set of genes encoding for the various putative DNA methyltransferases, 5-methylcytosine DNA glycosylases, and small interference RNA (siRNA) pathway-related proteins showed that, relative to the rice parental line, heritable perturbation in expression of 12 out of the 13 genes occurred in the mutator-phenotype and its sefled progenies. CONCLUSION: Transgenerational epigenetic instability in the form of altered cytosine methylation and its associated TE activity occurred in a rice mutator-phenotype produced by pollinating the rice stigma with pollens of O. biennis. Heritably perturbed homeostatic expression-state of genes involved in maintenance of chromatin structure is likely an underlying cause for the alien pollination-induced transgenerational epigenetic/genetic instability, and which occurred apparently without entailing genome merger or genetic introgression

A mobile polar atmospheric parameter measurement system: II. First atmospheric turbulence observation at Antarctic Taishan Station

This is the second paper of a series devoted to atmospheric optical turbulence Cn 2 observation using a mobile polar atmospheric parameter measurement system. We present the initial results of Cn 2 measurement at Antarctic Taishan Station using micro-thermal sensors and a three-dimensional sonic anemometer at height ~2.0 m above the snow surface. The site testing experiments were carried out during the 30th Chinese National Antarctic Research Expedition (CHINARE). We collected about 1 000 h of data between 30 December 2013 and 10 February 2014. The Cn2 curve exhibits clear daily structures, with two peaks around midnight and midday and two troughs around 7:30 and 17:00 local time (UTC+5). The mean Cn2 is 2.7×10−15 m−2/3 and the 25th and 75th percentiles of the Cn2 cumulative distribution are 9.6×10−16 m−2/3 and 6.2×10−15 m−2/3, respectively. Meteorological parameters such as temperature, relative humidity, wind speed, and air pressure are also presented

The efficacy of homestyle rehabilitation on negative symptoms in chronic schizophrenia: A randomized controlled trial

ObjectiveSchizophrenia is a debilitating mental disorder with a high disability rate that is characterized by negative symptoms such as apathy, hyperactivity, and anhedonia that can make daily life challenging and impair social functioning. In this study, we aim to investigate the effectiveness of homestyle rehabilitation in mitigating these negative symptoms and associated factors.MethodsA randomized controlled trial was conducted to compare the efficacy of hospital rehabilitation and homestyle rehabilitation for negative symptoms in 100 individuals diagnosed with schizophrenia. The participants were divided randomly into two groups, each persisting for 3 months. The primary outcome measures were the Scale for Assessment of Negative Symptoms (SANS) and Global Assessment of Functioning (GAF). The secondary outcome measures included the Positive Symptom Assessment Scale (SAPS), Calgary Schizophrenia Depression Scale (CDSS), Simpson-Angus Scale (SAS), and Abnormal Involuntary Movement Scale (AIMS). The trial aimed to compare the effectiveness of the two rehabilitation methods.ResultsHomestyle rehabilitation for negative symptoms was found to be more effective than hospital rehabilitation, according to the changes in SANS (T = 2.07, p = 0.04). Further analysis using multiple regression indicated that improvements in depressive symptoms (T = 6.88, p &lt; 0.001) and involuntary motor symptoms (T = 2.75, p = 0.007) were associated with a reduction in negative symptoms.ConclusionHomestyle rehabilitation may have greater potential than hospital rehabilitation in improving negative symptoms, making it an effective rehabilitation model. Further research is necessary to investigate factors such as depressive symptoms and involuntary motor symptoms, which may be associated with the improvement of negative symptoms. Additionally, more attention should be given to addressing secondary negative symptoms in rehabilitation interventions

Mutations in TUBB8 and Human Oocyte Meiotic Arrest

BACKGROUND Human reproduction depends on the fusion of a mature oocyte with a sperm cell to form a fertilized egg. The genetic events that lead to the arrest of human oocyte maturation are unknown. METHODS We sequenced the exomes of five members of a four-generation family, three of whom had infertility due to oocyte meiosis I arrest. We performed Sanger sequencing of a candidate gene, TUBB8, in DNA samples from these members, additional family members, and members of 23 other affected families. The expression of TUBB8 and all other β-tubulin isotypes was assessed in human oocytes, early embryos, sperm cells, and several somatic tissues by means of a quantitative reverse- transcriptase–polymerase-chain-reaction assay. We evaluated the effect of the TUBB8 mutations on the assembly of the heterodimer consisting of one α-tubulin polypeptide and one β-tubulin polypeptide (α/β-tubulin heterodimer) in vitro, on microtubule architecture in HeLa cells, on microtubule dynamics in yeast cells, and on spindle assembly in mouse and human oocytes. RESULTS We identified seven mutations in the primate-specific gene TUBB8 that were responsible for oocyte meiosis I arrest in 7 of the 24 families. TUBB8 expression is unique to oocytes and the early embryo, in which this gene accounts for almost all the expressed β-tubulin. The mutations affect chaperone-dependent folding and assembly of the α/β-tubulin heterodimer, disrupt microtubule behavior on expression in cultured cells, alter microtubule dynamics in vivo, and cause catastrophic spindle-assembly defects and maturation arrest on expression in mouse and human oocytes. CONCLUSIONS TUBB8 mutations have dominant-negative effects that disrupt microtubule behavior and oocyte meiotic spindle assembly and maturation, causing female infertility. (Funded by the National Basic Research Program of China and others.

Implicating genes, pleiotropy, and sexual dimorphism at blood lipid loci through multi-ancestry meta-analysis

Publisher Copyright: © 2022, The Author(s).Background: Genetic variants within nearly 1000 loci are known to contribute to modulation of blood lipid levels. However, the biological pathways underlying these associations are frequently unknown, limiting understanding of these findings and hindering downstream translational efforts such as drug target discovery. Results: To expand our understanding of the underlying biological pathways and mechanisms controlling blood lipid levels, we leverage a large multi-ancestry meta-analysis (N = 1,654,960) of blood lipids to prioritize putative causal genes for 2286 lipid associations using six gene prediction approaches. Using phenome-wide association (PheWAS) scans, we identify relationships of genetically predicted lipid levels to other diseases and conditions. We confirm known pleiotropic associations with cardiovascular phenotypes and determine novel associations, notably with cholelithiasis risk. We perform sex-stratified GWAS meta-analysis of lipid levels and show that 3–5% of autosomal lipid-associated loci demonstrate sex-biased effects. Finally, we report 21 novel lipid loci identified on the X chromosome. Many of the sex-biased autosomal and X chromosome lipid loci show pleiotropic associations with sex hormones, emphasizing the role of hormone regulation in lipid metabolism. Conclusions: Taken together, our findings provide insights into the biological mechanisms through which associated variants lead to altered lipid levels and potentially cardiovascular disease risk.Peer reviewe

Implicating genes, pleiotropy, and sexual dimorphism at blood lipid loci through multi-ancestry meta-analysis

Funding GMP, PN, and CW are supported by NHLBI R01HL127564. GMP and PN are supported by R01HL142711. AG acknowledge support from the Wellcome Trust (201543/B/16/Z), European Union Seventh Framework Programme FP7/2007–2013 under grant agreement no. HEALTH-F2-2013–601456 (CVGenes@Target) & the TriPartite Immunometabolism Consortium [TrIC]-Novo Nordisk Foundation’s Grant number NNF15CC0018486. JMM is supported by American Diabetes Association Innovative and Clinical Translational Award 1–19-ICTS-068. SR was supported by the Academy of Finland Center of Excellence in Complex Disease Genetics (Grant No 312062), the Finnish Foundation for Cardiovascular Research, the Sigrid Juselius Foundation, and University of Helsinki HiLIFE Fellow and Grand Challenge grants. EW was supported by the Finnish innovation fund Sitra (EW) and Finska Läkaresällskapet. CNS was supported by American Heart Association Postdoctoral Fellowships 15POST24470131 and 17POST33650016. Charles N Rotimi is supported by Z01HG200362. Zhe Wang, Michael H Preuss, and Ruth JF Loos are supported by R01HL142302. NJT is a Wellcome Trust Investigator (202802/Z/16/Z), is the PI of the Avon Longitudinal Study of Parents and Children (MRC & WT 217065/Z/19/Z), is supported by the University of Bristol NIHR Biomedical Research Centre (BRC-1215–2001) and the MRC Integrative Epidemiology Unit (MC_UU_00011), and works within the CRUK Integrative Cancer Epidemiology Programme (C18281/A19169). Ruth E Mitchell is a member of the MRC Integrative Epidemiology Unit at the University of Bristol funded by the MRC (MC_UU_00011/1). Simon Haworth is supported by the UK National Institute for Health Research Academic Clinical Fellowship. Paul S. de Vries was supported by American Heart Association grant number 18CDA34110116. Julia Ramierz acknowledges support by the People Programme of the European Union’s Seventh Framework Programme grant n° 608765 and Marie Sklodowska-Curie grant n° 786833. Maria Sabater-Lleal is supported by a Miguel Servet contract from the ISCIII Spanish Health Institute (CP17/00142) and co-financed by the European Social Fund. Jian Yang is funded by the Westlake Education Foundation. Olga Giannakopoulou has received funding from the British Heart Foundation (BHF) (FS/14/66/3129). CHARGE Consortium cohorts were supported by R01HL105756. Study-specific acknowledgements are available in the Additional file 32: Supplementary Note. The views expressed in this manuscript are those of the authors and do not necessarily represent the views of the National Heart, Lung, and Blood Institute; the National Institutes of Health; or the U.S. Department of Health and Human Services.Peer reviewedPublisher PD

Implicating genes, pleiotropy, and sexual dimorphism at blood lipid loci through multi-ancestry meta-analysis

Abstract Background Genetic variants within nearly 1000 loci are known to contribute to modulation of blood lipid levels. However, the biological pathways underlying these associations are frequently unknown, limiting understanding of these findings and hindering downstream translational efforts such as drug target discovery. Results To expand our understanding of the underlying biological pathways and mechanisms controlling blood lipid levels, we leverage a large multi-ancestry meta-analysis (N = 1,654,960) of blood lipids to prioritize putative causal genes for 2286 lipid associations using six gene prediction approaches. Using phenome-wide association (PheWAS) scans, we identify relationships of genetically predicted lipid levels to other diseases and conditions. We confirm known pleiotropic associations with cardiovascular phenotypes and determine novel associations, notably with cholelithiasis risk. We perform sex-stratified GWAS meta-analysis of lipid levels and show that 3–5% of autosomal lipid-associated loci demonstrate sex-biased effects. Finally, we report 21 novel lipid loci identified on the X chromosome. Many of the sex-biased autosomal and X chromosome lipid loci show pleiotropic associations with sex hormones, emphasizing the role of hormone regulation in lipid metabolism. Conclusions Taken together, our findings provide insights into the biological mechanisms through which associated variants lead to altered lipid levels and potentially cardiovascular disease risk