Acidithiobacillus ferrooxidans is a major participant in consortia of microorganisms used for the industrial recovery of copper (bioleaching or biomining). It is a chemolithoautrophic, ...gamma-proteobacterium using energy from the oxidation of iron- and sulfur-containing minerals for growth. It thrives at extremely low pH (pH 1-2) and fixes both carbon and nitrogen from the atmosphere. It solubilizes copper and other metals from rocks and plays an important role in nutrient and metal biogeochemical cycling in acid environments. The lack of a well-developed system for genetic manipulation has prevented thorough exploration of its physiology. Also, confusion has been caused by prior metabolic models constructed based upon the examination of multiple, and sometimes distantly related, strains of the microorganism.
The genome of the type strain A. ferrooxidans ATCC 23270 was sequenced and annotated to identify general features and provide a framework for in silico metabolic reconstruction. Earlier models of iron and sulfur oxidation, biofilm formation, quorum sensing, inorganic ion uptake, and amino acid metabolism are confirmed and extended. Initial models are presented for central carbon metabolism, anaerobic metabolism (including sulfur reduction, hydrogen metabolism and nitrogen fixation), stress responses, DNA repair, and metal and toxic compound fluxes.
Bioinformatics analysis provides a valuable platform for gene discovery and functional prediction that helps explain the activity of A. ferrooxidans in industrial bioleaching and its role as a primary producer in acidic environments. An analysis of the genome of the type strain provides a coherent view of its gene content and metabolic potential.
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DOBA, IZUM, KILJ, NUK, PILJ, PNG, SAZU, SIK, UILJ, UKNU, UL, UM, UPUK
dictyBase (http://dictybase.org), the model organism database for Dictyostelium discoideum, includes the complete genome sequence and expression data for this organism. Relevant literature is ...integrated into the database, and gene models and functional annotation are manually curated from experimental results and comparative multigenome analyses. dictyBase has recently expanded to include the genome sequences of three additional Dictyostelids and has added new software tools to facilitate multigenome comparisons. The Dicty Stock Center, a strain and plasmid repository for Dictyostelium research, has relocated to Northwestern University in 2009. This allowed us integrating all Dictyostelium resources to better serve the research community. In this chapter, we will describe how to navigate the Web site and highlight some of our newer improvements.
We report here the sequencing and analysis of the genome of the nitrogen-fixing endophyte, Klebsiella pneumoniae 342. Although K. pneumoniae 342 is a member of the enteric bacteria, it serves as a ...model for studies of endophytic, plant-bacterial associations due to its efficient colonization of plant tissues (including maize and wheat, two of the most important crops in the world), while maintaining a mutualistic relationship that encompasses supplying organic nitrogen to the host plant. Genomic analysis examined K. pneumoniae 342 for the presence of previously identified genes from other bacteria involved in colonization of, or growth in, plants. From this set, approximately one-third were identified in K. pneumoniae 342, suggesting additional factors most likely contribute to its endophytic lifestyle. Comparative genome analyses were used to provide new insights into this question. Results included the identification of metabolic pathways and other features devoted to processing plant-derived cellulosic and aromatic compounds, and a robust complement of transport genes (15.4%), one of the highest percentages in bacterial genomes sequenced. Although virulence and antibiotic resistance genes were predicted, experiments conducted using mouse models showed pathogenicity to be attenuated in this strain. Comparative genomic analyses with the presumed human pathogen K. pneumoniae MGH78578 revealed that MGH78578 apparently cannot fix nitrogen, and the distribution of genes essential to surface attachment, secretion, transport, and regulation and signaling varied between each genome, which may indicate critical divergences between the strains that influence their preferred host ranges and lifestyles (endophytic plant associations for K. pneumoniae 342 and presumably human pathogenesis for MGH78578). Little genome information is available concerning endophytic bacteria. The K. pneumoniae 342 genome will drive new research into this less-understood, but important category of bacterial-plant host relationships, which could ultimately enhance growth and nutrition of important agricultural crops and development of plant-derived products and biofuels.
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DOBA, IZUM, KILJ, NUK, PILJ, PNG, SAZU, SIK, UILJ, UKNU, UL, UM, UPUK
Advanced heart failure (HF) is characterized by high morbidity and mortality. Conventional therapy may not sufficiently reduce patient suffering and maximize quality of life.
The authors investigated ...whether an interdisciplinary palliative care intervention in addition to evidence-based HF care improves certain outcomes.
The authors randomized 150 patients with advanced HF between August 15, 2012, and June 25, 2015, to usual care (UC) (n = 75) or UC plus a palliative care intervention (UC + PAL) (n = 75) at a single center. Primary endpoints were 2 quality-of-life measurements, the Kansas City Cardiomyopathy Questionnaire (KCCQ) overall summary and the Functional Assessment of Chronic Illness Therapy-Palliative Care scale (FACIT-Pal), assessed at 6 months. Secondary endpoints included assessments of depression and anxiety (measured via the Hospital Anxiety and Depression Scale HADS), spiritual well-being (measured via the FACIT-Spiritual Well-Being scale FACIT-Sp), hospitalizations, and mortality.
Patients randomized to UC + PAL versus UC alone had clinically significant incremental improvement in KCCQ and FACIT-Pal scores from randomization to 6 months (KCCQ difference = 9.49 points, 95% confidence interval CI: 0.94 to 18.05, p = 0.030; FACIT-Pal difference = 11.77 points, 95% CI: 0.84 to 22.71, p = 0.035). Depression improved in UC + PAL patients (HADS-depression difference = -1.94 points; p = 0.020) versus UC-alone patients, with similar findings for anxiety (HADS-anxiety difference = -1.83 points; p = 0.048). Spiritual well-being was improved in UC + PAL versus UC-alone patients (FACIT-Sp difference = 3.98 points; p = 0.027). Randomization to UC + PAL did not affect rehospitalization or mortality.
An interdisciplinary palliative care intervention in advanced HF patients showed consistently greater benefits in quality of life, anxiety, depression, and spiritual well-being compared with UC alone. (Palliative Care in Heart Failure PAL-HF; NCT01589601).
While survival after acute myocardial infarction has improved substantially, older adults remain at heightened risk for hospital readmissions and death. Evidence for the role of cognitive impairment ...in older myocardial infarction survivors’ risk for these outcomes is limited.
3041 patients aged ≥75 years hospitalized with acute myocardial infarction (mean age 82 ± 5 years, 56% male) recruited from 94 US hospitals. Cognition was assessed using the Telephone Interview for Cognitive Status; scores of <27 and <22 indicated mild and moderate/severe impairment, respectively. Readmissions and death at 6 months post-discharge were ascertained via participant report and medical record review. Associations between cognition and outcomes were evaluated with multivariable-adjusted logistic regression.
Mild and moderate/severe cognitive impairment were present in 11% and 6% of the cohort, respectively. Readmission and death at 6 months occurred in 41% and 9% of participants, respectively. Mild and moderate/severe cognitive impairment were associated with increased risk of readmission (odds ratio OR 1.36; 95% confidence interval CI, 1.08-1.72 and OR 1.58; 95% CI, 1.18-2.12, respectively) and death (OR 2.19; 95% CI, 1.54-3.11 and OR 3.82; 95% CI, 2.63-5.56, respectively) in unadjusted analyses. Significant associations between moderate/severe cognitive impairment and death (OR 1.69; 95% CI, 1.10-2.59) persisted after adjustment for demographics, myocardial infarction characteristics, comorbidity burden, functional status, and depression, but not for readmissions.
Moderate-to-severe cognitive impairment is associated with heightened risk of death in older acute myocardial infarction patients in the months after hospitalization, but not with readmission. Routine cognitive screening may identify older myocardial infarction survivors at risk for poor outcomes who may benefit from closer oversight and support in the post-discharge period.
Histone methyltransferases (HMTases), as chromatin modifiers, regulate the transcriptomic landscape in normal development as well in diseases such as cancer. Here, we molecularly order two HMTases, ...EZH2 and MMSET, that have established genetic links to oncogenesis. EZH2, which mediates histone H3K27 trimethylation and is associated with gene silencing, was shown to be coordinately expressed and function upstream of MMSET, which mediates H3K36 dimethylation and is associated with active transcription. We found that the EZH2-MMSET HMTase axis is coordinated by a microRNA network and that the oncogenic functions of EZH2 require MMSET activity. Together, these results suggest that the EZH2-MMSET HMTase axis coordinately functions as a master regulator of transcriptional repression, activation, and oncogenesis and may represent an attractive therapeutic target in cancer.
► Coordinated regulation of EZH2 and MMSET in cancer progression ► EZH2 regulates MMSET and its H3K36me2 mark through microRNAs ► MMSET is a downstream mediator of EZH2 oncogenic function ► MMSET overexpression promotes diverse oncogenic phenotypes in vitro and in vivo
Abstract Within the last decade, advancements in left ventricular assist device (LVAD) therapy have allowed end-stage heart failure patients to live longer and with better quality of life. Like other ...life-saving interventions, however, there remains the risk of complications including infections, bleeding episodes, and stroke. The candidate for LVAD therapy faces complex challenges going forward, both physical and psychological, many of which may benefit from the application of palliative care principles by trained specialists. Despite these advantages, palliative care remains underused in many advanced heart failure programs. Here, we describe the benefits of palliative care, barriers to use within heart failure, and specific applications to the integrated care of patients on mechanical circulatory support.
The genome of C. jejuni RM1221 is a single circular chromosome, 1,777,831 bp in length, with an average G+C content of 30.31%. There are a total of 1,884 predicted coding regions in the genome with ...an average ORF length of 885 bp. Ninety-four percent of the genome represents coding sequence. Putative role assignments could be made for 1,124 of the ORFs (60%) (Table 1; Figure S1). The bacterium was found to belong to multilocus sequence type (MLST) 354 and FlaA short variable region (SVR) 33, which belongs to clonal complex 354, whose members are associated with human disease or chickens/chicken meat (Table 1) 34. The genome features for the unfinished Campylobacter genomes were based on automated analysis and are presented in Table 1. The average coverage of the unfinished genomes was found to be 8.5-fold for C. coli RM2228, 16.5-fold for C. lari RM2100, and 9.0-fold for C. upsaliensis RM3195 for those contigs used to construct the pseudomolecules. The ambiguity rate (number of consensus-altering ambiguities per basepair) was determined to be between 1:54,000 and 1:93,000 for these unedited, unfinished genomes at 8-fold depth of coverage. The genomic structure of C. jejuni RM1221 is syntenic with the genome of C. jejuni NCTC 11168, and is disrupted by inserted prophages/genomic islands in RM1221 (see below), and ORFs within the capsular (extracellular) polysaccharide (EP) loci in NCTC 11168 (Figures 1A and S2). The C. coli RM2228 genomic structure also has a considerable amount of synteny with C. jejuni RM1221, sharing similar breakpoints, as observed in the C. jejuni comparisons, but displaying evidence of rearrangements about the oriC, as described for other bacterial genomes 35. In contrast, C. lari and C. upsaliensis possess little if any synteny with C. jejuni RM1221.
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DOBA, IZUM, KILJ, NUK, PILJ, PNG, SAZU, SIK, UILJ, UKNU, UL, UM, UPUK
Introduction: Cochlear implantation has become an increasingly common strategy for aural rehabilitation in patients with severe to profound hearing loss who no longer benefit from conventional ...amplification. In conjunction, immunosuppressive therapies (e.g. disease-modifying anti rheumatic drugs (DMARDs) have become the keystone of management in numerous autoimmune conditions. Given the increasing prevalence of both, a greater proportion of patients will undergo cochlear implantation while on immune-modulating medications. While these medications are usually well tolerated, immunosuppression may put patients a higher risk for device infections. At present, this is not extensively studied within the cochlear implant literature. Methods: We conducted a retrospective chart review and review of the literature. Results: We present the case of an 81-year-old male who experienced wound dehiscence and infection secondary to leflunomide use for treatment of rheumatoid arthritis. Resolution of these issues was noted with a therapeutic drug holiday, and the patient has subsequently undergone re-implantation without issue. Conclusions: The case highlights a potential CI-associated wound complication in the setting of DMARD therapy. Given the increasing prevalence of both CIs and immunosuppressive therapy, future study on the potential for interaction is warranted to identify the best management strategy in the perioperative setting.
We report here the sequencing and analysis of the genome of the thermophilic bacterium Carboxydothermus hydrogenoformans Z-2901. This species is a model for studies of hydrogenogens, which are ...diverse bacteria and archaea that grow anaerobically utilizing carbon monoxide (CO) as their sole carbon source and water as an electron acceptor, producing carbon dioxide and hydrogen as waste products. Organisms that make use of CO do so through carbon monoxide dehydrogenase complexes. Remarkably, analysis of the genome of C. hydrogenoformans reveals the presence of at least five highly differentiated anaerobic carbon monoxide dehydrogenase complexes, which may in part explain how this species is able to grow so much more rapidly on CO than many other species. Analysis of the genome also has provided many general insights into the metabolism of this organism which should make it easier to use it as a source of biologically produced hydrogen gas. One surprising finding is the presence of many genes previously found only in sporulating species in the Firmicutes Phylum. Although this species is also a Firmicutes, it was not known to sporulate previously. Here we show that it does sporulate and because it is missing many of the genes involved in sporulation in other species, this organism may serve as a "minimal" model for sporulation studies. In addition, using phylogenetic profile analysis, we have identified many uncharacterized gene families found in all known sporulating Firmicutes, but not in any non-sporulating bacteria, including a sigma factor not known to be involved in sporulation previously.
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DOBA, IZUM, KILJ, NUK, PILJ, PNG, SAZU, SIK, UILJ, UKNU, UL, UM, UPUK
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