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Plasmid genes or regions that are conditionally lethal to Escherichia coli have been called kil and those lethal to Klebsiella but not to E. coli have been called kik. Both classes of genes are found in or close to the N pilus region of the plasmid pCU1 and the closely related plasmid pKM101. Here we describe two new and overlapping lethal genes that are located between kikA and traA of the plasmid pCU1 and display host specificity. KilC is lethal in E. coli and Klebsiella while kikC is lethal only in Klebsiella. The previously identified korA gene is sufficient to override the lethality of kilC in trans or in cis but is insufficient to override kikC. kilC expression in E. coli leads to cell death accompanied by an increase in average cell length without affecting septum formation. 相似文献
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Sreejyothi Sankararaman Renjini Ammini Raj Vimal Swapna Mohanachandran Nair Sindhu Sankararaman Sankaranarayana Iyer 《Journal of biological physics》2021,47(2):103-115
Journal of Biological Physics - The paper delves into the plausibility of applying fractal, spectral, and nonlinear time series analyses for lung auscultation. The thirty-five sound signals of... 相似文献
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Lakshminarayan M. Iyer Dapeng Zhang A. Maxwell Burroughs L. Aravind 《Nucleic acids research》2013,41(16):7635-7655
Discovery of the TET/JBP family of dioxygenases that modify bases in DNA has sparked considerable interest in novel DNA base modifications and their biological roles. Using sensitive sequence and structure analyses combined with contextual information from comparative genomics, we computationally characterize over 12 novel biochemical systems for DNA modifications. We predict previously unidentified enzymes, such as the kinetoplastid J-base generating glycosyltransferase (and its homolog GREB1), the catalytic specificity of bacteriophage TET/JBP proteins and their role in complex DNA base modifications. We also predict the enzymes involved in synthesis of hypermodified bases such as alpha-glutamylthymine and alpha-putrescinylthymine that have remained enigmatic for several decades. Moreover, the current analysis suggests that bacteriophages and certain nucleo-cytoplasmic large DNA viruses contain an unexpectedly diverse range of DNA modification systems, in addition to those using previously characterized enzymes such as Dam, Dcm, TET/JBP, pyrimidine hydroxymethylases, Mom and glycosyltransferases. These include enzymes generating modified bases such as deazaguanines related to queuine and archaeosine, pyrimidines comparable with lysidine, those derived using modified S-adenosyl methionine derivatives and those using TET/JBP-generated hydroxymethyl pyrimidines as biosynthetic starting points. We present evidence that some of these modification systems are also widely dispersed across prokaryotes and certain eukaryotes such as basidiomycetes, chlorophyte and stramenopile alga, where they could serve as novel epigenetic marks for regulation or discrimination of self from non-self DNA. Our study extends the role of the PUA-like fold domains in recognition of modified nucleic acids and predicts versions of the ASCH and EVE domains to be novel ‘readers’ of modified bases in DNA. These results open opportunities for the investigation of the biology of these systems and their use in biotechnology. 相似文献
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BackgroundMany cardiac patients need and undergo device implants. Veterans’ preferences regarding post-mortem handling of devices are not known. Cardiac patients in low- and middle-income countries who need but cannot afford devices rely on donations. Charitable organizations have successfully provided devices for reuse to such patients.ObjectiveWe estimated the number of devices with potential for possible reuse in a veteran population.MethodsBetween January and December 2008, at a tertiary medical center, veterans with implanted cardiac devices were surveyed using a questionnaire for their preferences regarding post-mortem handling. One choice was donation to charity for reuse. Although altruistic, it is unclear what percent of such devices have reuse potential. Retrospective chart review of veterans who underwent device implants between 1992 and 2007 identified a cohort of patients with Implantable Cardiac Defibrillators (ICDs) who had died by April 31st 2009. In this cohort, ICDs implanted in the year preceding the patient’s death were counted as having reuse potential.Results94 of 97 veterans completed the survey. 56% were unaware of how devices are handled after death. The top three preferences for postmortem handling were: return to manufacturer, return to hospital and donation for reuse. 88% were willing to sign an advance device directive. Retrospective review identified 161 veterans who had received 301 ICDs. Of these, 77 ICDs (25%) had median reuse potential of 3.1 years.ConclusionIn a VA cohort of deceased patients a substantial proportion of devices had reuse potential. Further research is needed to direct health policy. 相似文献
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A proteomics approach to identifying key protein targets involved in VEGF inhibitor mediated attenuation of bleomycin‐induced pulmonary fibrosis
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Yogesh M. Kulkarni Sucharita Dutta Anand Krishnan V. Iyer Rajkumar Venkatadri Vivek Kaushik Vani Ramesh Clayton A. Wright Oliver John Semmes Juan S. Yakisich Neelam Azad 《Proteomics》2016,16(1):33-46
Idiopathic pulmonary fibrosis (IPF) is a progressive lung disease with a life expectancy of less than 5 years post diagnosis for most patients. Poor molecular characterization of IPF has led to insufficient understanding of the pathogenesis of the disease, resulting in lack of effective therapies. In this study, we have integrated a label‐free LC‐MS based approach with systems biology to identify signaling pathways and regulatory nodes within protein interaction networks that govern phenotypic changes that may lead to IPF. Ingenuity Pathway Analysis of proteins modulated in response to bleomycin treatment identified PI3K/Akt and Wnt signaling as the most significant profibrotic pathways. Similar analysis of proteins modulated in response to vascular endothelial growth factor (VEGF) inhibitor (CBO‐P11) treatment identified natural killer cell signaling and PTEN signaling as the most significant antifibrotic pathways. Mechanistic/mammalian target of rapamycin (mTOR) and extracellular signal‐regulated kinase (ERK) were identified to be key mediators of pro‐ and antifibrotic response, where bleomycin (BLM) treatment resulted in increased expression and VEGF inhibitor treatment attenuated expression of mTOR and ERK. Using a BLM mouse model of pulmonary fibrosis and VEGF inhibitor CBO‐P11 as a therapeutic measure, we identified a comprehensive set of signaling pathways and proteins that contribute to the pathogenesis of pulmonary fibrosis that can be targeted for therapy against this fatal disease. 相似文献
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Julia A. Sabet Lara K. Park Lakshmanan K. Iyer Albert K. Tai Gar Yee Koh Anna C. Pfalzer Laurence D. Parnell Joel B. Mason Zhenhua Liu Alexander J. Byun Jimmy W. Crott 《PloS one》2016,11(3)
Background
The importance of maternal nutrition to offspring health and risk of disease is well established. Emerging evidence suggests paternal diet may affect offspring health as well.Objective
In the current study we sought to determine whether modulating pre-conception paternal B vitamin intake alters intestinal tumor formation in offspring. Additionally, we sought to identify potential mechanisms for the observed weight differential among offspring by profiling hepatic gene expression and lipid content.Methods
Male Apc1638N mice (prone to intestinal tumor formation) were fed diets containing replete (control, CTRL), mildly deficient (DEF), or supplemental (SUPP) quantities of vitamins B2, B6, B12, and folate for 8 weeks before mating with control-fed wild type females. Wild type offspring were euthanized at weaning and hepatic gene expression profiled. Apc1638N offspring were fed a replete diet and euthanized at 28 weeks of age to assess tumor burden.Results
No differences in intestinal tumor incidence or burden were found between male Apc1638N offspring of different paternal diet groups. Although in female Apc1638N offspring there were no differences in tumor incidence or multiplicity, a stepwise increase in tumor volume with increasing paternal B vitamin intake was observed. Interestingly, female offspring of SUPP and DEF fathers had a significantly lower body weight than those of CTRL fed fathers. Moreover, hepatic trigylcerides and cholesterol were elevated 3-fold in adult female offspring of SUPP fathers. Weanling offspring of the same fathers displayed altered expression of several key lipid-metabolism genes. Hundreds of differentially methylated regions were identified in the paternal sperm in response to DEF and SUPP diets. Aside from a few genes including Igf2, there was a striking lack of overlap between these genes differentially methylated in sperm and differentially expressed in offspring.Conclusions
In this animal model, modulation of paternal B vitamin intake prior to mating alters offspring weight gain, lipid metabolism and tumor growth in a sex-specific fashion. These results highlight the need to better define how paternal nutrition affects the health of offspring. 相似文献50.
Mark Pennington Aleksandra Gentry-Maharaj Chloe Karpinskyj Alec Miners Julie Taylor Ranjit Manchanda Rema Iyer Michelle Griffin Andy Ryan Ian Jacobs Usha Menon Rosa Legood 《PloS one》2016,11(11)
BackgroundThere is limited evidence on the costs of Endometrial Cancer (EC) by stage of disease. We estimated the long-term secondary care costs of EC according to stage at diagnosis in an English population-based cohort.MethodsWomen participating in UKCTOCS and diagnosed with EC following enrolment (2001–2005) and prior to 31st Dec 2009 were identified to have EC through multiple sources. Survival was calculated through data linkage to death registry. Costs estimates were derived from hospital records accessed from Hospital Episode Statistics (HES) with additional patient level covariates derived from case notes and patient questionnaires. Missing and censored data was imputed using Multiple Imputation. Regression analysis of cost and survival was undertaken.Results491 of 641 women with EC were included. Five year total costs were strongly dependent on stage, ranging from £9,475 (diagnosis at stage IA/IB) to £26,080 (diagnosis at stage III). Stage, grade and BMI were the strongest predictors of costs. The majority of costs for stage I/II EC were incurred in the first six months after diagnosis while for stage III / IV considerable costs accrued after the first six months.ConclusionsIn addition to survival advantages, there are significant cost savings if patients with EC are detected earlier. 相似文献