431 research outputs found

    A combinatorial TIR1/AFB–Aux/IAA co-receptor system for differential sensing of auxin

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    The plant hormone auxin regulates virtually every aspect of plant growth and development. Auxin acts by binding the F-box protein transport inhibitor response 1 (TIR1) and promotes the degradation of the AUXIN/INDOLE-3-ACETIC ACID (Aux/IAA) transcriptional repressors. Here we show that efficient auxin binding requires assembly of an auxin co-receptor complex consisting of TIR1 and an Aux/IAA protein. Heterologous experiments in yeast and quantitative IAA binding assays using purified proteins showed that different combinations of TIR1 and Aux/IAA proteins form co-receptor complexes with a wide range of auxin-binding affinities. Auxin affinity seems to be largely determined by the Aux/IAA. As there are 6 TIR1/AUXIN SIGNALING F-BOX proteins (AFBs) and 29 Aux/IAA proteins in Arabidopsis thaliana, combinatorial interactions may result in many co-receptors with distinct auxin-sensing properties. We also demonstrate that the AFB5–Aux/IAA co-receptor selectively binds the auxinic herbicide picloram. This co-receptor system broadens the effective concentration range of the hormone and may contribute to the complexity of auxin response

    Clinical profiles of patients colonized or infected with extended-spectrum beta-lactamase producing Enterobacteriaceae isolates: a 20 month retrospective study at a Belgian University Hospital

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    <p>Abstract</p> <p>Background</p> <p>Description of the clinical pictures of patients colonized or infected by ESBL-producing <it>Enterobacteriaceae </it>isolates and admitted to hospital are rather scarce in Europe. However, a better delineation of the clinical patterns associated with the carriage of ESBL-producing isolates may allow healthcare providers to identify more rapidly at risk patients. This matter is of particular concern because of the growing proportion of ESBL-producing <it>Enterobacteriaceae </it>species isolates worldwide.</p> <p>Methods</p> <p>We undertook a descriptive analysis of 114 consecutive patients in whom ESBL-producing <it>Enterobacteriaceae </it>isolates were collected from clinical specimens over a 20-month period. Clinical data were obtained through retrospective analysis of medical record charts. Microbiological cultures were carried out by standard laboratory methods.</p> <p>Results</p> <p>The proportion of ESBL-producing <it>Enterobacteriaceae </it>strains after exclusion of duplicate isolates was 4.5% and the incidence rate was 4.3 cases/1000 patients admitted. Healthcare-associated acquisition was important (n = 104) while community-acquisition was less frequently found (n = 10). Among the former group, two-thirds of the patients were aged over 65 years and 24% of these were living in nursing homes. Sixty-eight (65%) of the patients with healthcare-associated ESBL, were considered clinically infected. In this group, the number and severity of co-morbidities was high, particularly including diabetes mellitus and chronic renal insufficiency. Other known risk factors for ESBL colonization or infection such as prior antibiotic exposure, urinary catheter or previous hospitalisation were also often found. The four main diagnostic categories were: urinary tract infections, lower respiratory tract infections, septicaemia and intra-abdominal infections. For hospitalized patients, the median hospital length of stay was 23 days and the average mortality rate during hospitalization was 13% (Confidence Interval 95%: 7-19). <it>Escherichia coli</it>, by far, accounted as the most common ESBL-producing <it>Enterobacteriaceae </it>species (77/114; [68%]) while CTX-M-1 group was by far the most prevalent ESBL enzyme (n = 56).</p> <p>Conclusion</p> <p>In this retrospective study, the clinical profiles of patients carrying healthcare-associated ESBL-producing <it>Enterobacteriacae </it>is characterized by a high prevalence rate of several major co-morbidities and potential known risk factors. Both, the length of hospital stay and overall hospital mortality rates were particularly high. A prospective case-control matched study should be designed and performed in order to control for possible inclusion bias.</p

    Consumption of single cigarettes and quitting behavior: A longitudinal analysis of Mexican smokers

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    <p>Abstract</p> <p>Background</p> <p>Previous cross-sectional research has suggested single cigarettes could either promote or inhibit consumption. The present study aimed to assess the effects of single cigarette availability and consumption on downstream quit behavior.</p> <p>Methods</p> <p>We analyzed population-based, longitudinal data from adult smokers who participated in the 2008 and 2010 administrations of the International Tobacco Control Policy Evaluation Survey in Mexico.</p> <p>Results</p> <p>At baseline, 30% of smokers saw single cigarettes for sale on a daily basis, 17% bought singles at their last purchase, and 7% bought singles daily. Smokers who most frequently purchased singles, both in general and specifically to control their consumption, were no more likely to attempt to quit over the 14 month follow-up period than those who did not purchase singles. Frequency of buying singles to reduce consumption had a non-monotonic association with being quit at followup. The odds of being quit was only statistically significant when comparing those who had not bought singles to reduce consumption with those who had done so on a more irregular basis (AOR = 2.30; 95% CI 1.19, 4.45), whereas those who did so more regularly were no more likely to be quit at followup. Frequency of self-reported urges to smoke upon seeing singles for sale was unassociated with either quit attempts or being quit at followup.</p> <p>Conclusions</p> <p>These results suggest that the relationship between singles consumption and quit behavior is complex, with no clear evidence that singles either promote or inhibit downstream quit behavior.</p

    Taking the steps towards sustainable livestock: our multidisciplinary global farm platform journey

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    Implications The Global Farm Platform was conceived and established to explore multidisciplinary strategies for optimising the sustainability of ruminant livestock systems around the world. International sustainability issues are common, but the solutions are often region-specific; therefore, our farms, situated across all major agroclimatic zones, are a unique resource worldwide. Each farm is following ?steps to sustainable livestock? to improve their production system(s), thereby developing robust metrics to progress economic, environmental and social viability. The consortium works collaboratively to improve the sustainability of ruminants, which we argue are a vital component of global food systems, delivering both human and planetary health

    Design and Synthesis of a Quintessential Self-Transmissible IncX1 Plasmid, pX1.0

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    DNA exchange in bacteria via conjugative plasmids is believed to be among the most important contributing factors to the rapid evolution- and diversification rates observed in bacterial species. The IncX1 plasmids are particularly interesting in relation to enteric bacteria, and typically carry genetic loads like antibiotic resistance genes and virulence factors. So far, however, a “pure” version of these molecular parasites, without genetic loads, has yet to be isolated from the environment. Here we report the construction of pX1.0, a fully synthesized IncX1 plasmid capable of horizontal transfer between different enteric bacteria. The designed pX1.0 sequence was derived from the consensus gene content of five IncX1 plasmids and three other, more divergent, members of the same phylogenetic group. The pX1.0 plasmid was shown to replicate stably in E. coli with a plasmid DNA per total DNA ratio corresponding to approximately 3–9 plasmids per chromosome depending on the growth phase of the host. Through conjugation, pX1.0 was able to self-transfer horizontally into an isogenic strain of E. coli as well as into two additional species belonging to the family Enterobacteriaceae. Our results demonstrate the immediate applicability of recent advances made within the field of synthetic biology for designing and constructing DNA systems, previously existing only in silica

    First isolation report of Arcobacter cryaerophilus from a human diarrhea sample in Costa Rica

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    ABSTRACT Arcobacter cryaerophilus is an emerging enteropathogen and potential zoonotic agent transmitted by food and water. In Costa Rica, this bacterium has not been associated with cases of human gastroenteritis, even though it has been isolated from farm animals, especially poultry. This paper reports the first isolation of A. cryaerophilus from a human case of bloody watery diarrhea and the virulence genes associated with this isolate

    Exploring the Contextual Sensitivity of Factors that Determine Cell-to-Cell Variability in Receptor-Mediated Apoptosis

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    Stochastic fluctuations in gene expression give rise to cell-to-cell variability in protein levels which can potentially cause variability in cellular phenotype. For TRAIL (TNF-related apoptosis-inducing ligand) variability manifests itself as dramatic differences in the time between ligand exposure and the sudden activation of the effector caspases that kill cells. However, the contribution of individual proteins to phenotypic variability has not been explored in detail. In this paper we use feature-based sensitivity analysis as a means to estimate the impact of variation in key apoptosis regulators on variability in the dynamics of cell death. We use Monte Carlo sampling from measured protein concentration distributions in combination with a previously validated ordinary differential equation model of apoptosis to simulate the dynamics of receptor-mediated apoptosis. We find that variation in the concentrations of some proteins matters much more than variation in others and that precisely which proteins matter depends both on the concentrations of other proteins and on whether correlations in protein levels are taken into account. A prediction from simulation that we confirm experimentally is that variability in fate is sensitive to even small increases in the levels of Bcl-2. We also show that sensitivity to Bcl-2 levels is itself sensitive to the levels of interacting proteins. The contextual dependency is implicit in the mathematical formulation of sensitivity, but our data show that it is also important for biologically relevant parameter values. Our work provides a conceptual and practical means to study and understand the impact of cell-to-cell variability in protein expression levels on cell fate using deterministic models and sampling from parameter distributions
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