This review highlights available treatment options and their limitations, and provides direction for future investigative efforts to aid in the treatment of severe Enterococcus faecalis infections, ...namely infective endocarditis.
Abstract
Enterococci, one of the most common causes of hospital-associated infections, are responsible for substantial morbidity and mortality. Enterococcus faecalis, the more common and virulent species, causes serious high-inoculum infections, namely infective endocarditis, that are associated with cardiac surgery and mortality rates that remained unchanged for the last 30 years. The best cures for these infections are observed with combination antibiotic therapy; however, optimal treatment has not been fully elucidated. It is the purpose of this review to highlight treatment options and their limitations, and provide direction for future investigative efforts to aid in the treatment of these severe infections. While ampicillin plus ceftriaxone has emerged as a preferred treatment option, mortality rates continue to be high, and from a safety standpoint, ceftriaxone, unlike other cephalosporins, promotes colonization with vancomycin resistant-enterococci due to high biliary concentrations. More research is needed to improve patient outcomes from this high-mortality disease.
Up to 478 Gochu Asturcelta pig parents-offspring trios (61 different families) were genotyped using the Axiom_PigHDv1 Array to identify the causes of Mendelian errors (ME). Up to 545,364 SNPs were ...retained. Up to 40,540 SNPs gathering 292,297 allelic mismatches were identified and were overlapped with SINEs and LINEs (Sscrofa genome 11.1). Copy number variations (CNV) were called using PennCNV. ME were classified into eight different classes according to the trio member ("Trio" meaning no assignment) and the allele on which ME was identified: TrioA/B, FatherA/B, MotherA/B, OffspringA/B. Most ME occurred due to systematic causes: (a) those assigned to the Father, Mother or Offspring occurred by null or partial null alleles characterized by heterozygote deficiency, varied with family size, involved a low number of loci (6506), and gathered most mismatches (228,145); (b) TrioB errors varied with family size, covaried with SINEs, LINEs and CNV, and involved most ME loci (33,483) and mismatches (65,682); and (c) TrioA errors were non-systematic ME with no sampling bias involving 1.2% of mismatches only and a low number of loci (1939). The influence of TrioB errors on the overall genotyping quality may be low and, since CNV vary among populations, their removal should be considered in each particular dataset. ME assignable to the Father, Mother or Offspring may be consistent within technological platforms and may bias severely linkage or association studies. Most ME caused by null or partial null alleles can be removed using heterozygote deficiency without affecting the size of the datasets.
Summary
Positive selection is the driving force underpinning local adaptation and leaves footprints of selective sweeps on the underlying major genes. Quantifying the timing of selection and ...revealing the genetic bases of adaptation in plant species occurring in steep and varying environmental gradients are crucial to predict a species' ability to colonize new niches.
We use whole‐genome sequence data from six populations across three different habitats of the wild tomato species Solanum chilense to infer the past demographic history and search for genes under strong positive selection. We then correlate current and past climatic projections with the demographic history, allele frequencies, the age of selection events and distribution shifts.
Several selective sweeps occur at regulatory networks involved in root‐hair development in low altitude and response to photoperiod and vernalization in high‐altitude populations. These sweeps appear to occur in a concerted fashion in a given regulatory gene network at particular periods of substantial climatic change.
Using a unique combination of genome scans and modelling of past climatic data, we quantify the timing of selection at genes likely underpinning local adaptation to semiarid habitats.
We have observed that the dry-season length (DSL) has increased over southern Amazonia since 1979, primarily owing to a delay of its ending dates (dry-season end, DSE), and is accompanied by a ...prolonged fire season. A poleward shift of the subtropical jet over South America and an increase of local convective inhibition energy in austral winter (June–August) seem to cause the delay of the DSE in austral spring (September–November). These changes cannot be simply linked to the variability of the tropical Pacific and Atlantic Oceans. Although they show some resemblance to the effects of anthropogenic forcings reported in the literature, we cannot attribute them to this cause because of inadequate representation of these processes in the global climate models that were presented in the Intergovernmental Panel on Climate Change's Fifth Assessment Report. These models significantly underestimate the variability of the DSE and DSL and their controlling processes. Such biases imply that the future change of the DSE and DSL may be underestimated by the climate projections provided by the Intergovernmental Panel on Climate Change's Fifth Assessment Report models. Although it is not clear whether the observed increase of the DSL will continue in the future, were it to continue at half the rate of that observed, the long DSL and fire season that contributed to the 2005 drought would become the new norm by the late 21st century. The large uncertainty shown in this study highlights the need for a focused effort to better understand and simulate these changes over southern Amazonia.
We report mapping of a quantitative trait locus (QTL) with a major effect on bovine stature to a ∼780-kb interval using a Hidden Markov Model-based approach that simultaneously exploits linkage and ...linkage disequilibrium. We re-sequenced the interval in six sires with known QTL genotype and identified 13 clustered candidate quantitative trait nucleotides (QTNs) out of >9,572 discovered variants. We eliminated five candidate QTNs by studying the phenotypic effect of a recombinant haplotype identified in a breed diversity panel. We show that the QTL influences fetal expression of seven of the nine genes mapping to the ∼780-kb interval. We further show that two of the eight candidate QTNs, mapping to the PLAG1-CHCHD7 intergenic region, influence bidirectional promoter strength and affect binding of nuclear factors. By performing expression QTL analyses, we identified a splice site variant in CHCHD7 and exploited this naturally occurring null allele to exclude CHCHD7 as single causative gene.
We introduce a fully ab initio theory for inelastic scattering of any atom from any surface exciting single phonons, and apply the theory to helium scattering from Nb(100). The key aspect making our ...approach general is a direct first-principles evaluation of the scattering atom-electron vertex. By correcting misleading results from current state-of-the-art theories, this fully ab initio approach will be critical in guiding and interpreting experiments that adopt next-generation, nondestructive atomic beam scattering.
The targeting of two independent but synergistic enzymatic activities, histone deacetylases (HDACs, class I and HDAC6) and phosphodiesterase 5 (PDE5), has recently been validated as a potentially ...novel therapeutic approach for Alzheimer's disease (AD). Here we report the discovery of a new first-in-class small-molecule (CM-414) that acts as a dual inhibitor of PDE5 and HDACs. We have used this compound as a chemical probe to validate this systems therapeutics strategy, where an increase in the activation of cAMP/cGMP-responsive element-binding protein (CREB) induced by PDE5 inhibition, combined with moderate HDAC class I inhibition, leads to efficient histone acetylation. This molecule rescued the impaired long-term potentiation evident in hippocampal slices from APP/PS1 mice. Chronic treatment of Tg2576 mice with CM-414 diminished brain Aβ and tau phosphorylation (pTau) levels, increased the inactive form of GSK3β, reverted the decrease in dendritic spine density on hippocampal neurons, and reversed their cognitive deficits, at least in part by inducing the expression of genes related to synaptic transmission. Thus, CM-414 may serve as the starting point to discover balanced dual inhibitors with an optimal efficacy and safety profile for clinical testing on AD patients.
The problem of determining the trajectories to control greenhouse crop growth has traditionally been solved by using constrained optimization or applying artificial intelligence techniques. The ...economic profit has been used as the main criterion in most research on optimization to obtain adequate climatic control setpoints for the crop growth. This paper addresses the problem of greenhouse crop growth through a hierarchical control architecture governed by a high-level multiobjective optimization approach, where the solution to this problem is to find reference trajectories for diurnal and nocturnal temperatures (climate-related setpoints) and electrical conductivity (fertirrigation-related setpoints). The objectives are to maximize profit, fruit quality, and water-use efficiency, these being currently fostered by international rules. Illustrative results selected from those obtained in an industrial greenhouse during the last eight years are shown and described.
Wastewater treatment plants (WWTPs) have been developed as multifunctional systems that aim to eliminate pollutants present in wastewater, manage the sludge produced and improve energy efficiency. ...Specifically, sludge management accounts for the largest share in operational costs. Considering the relevant role of sludge treatment within the overall management scheme, this study aims to evaluate different alternatives and strategies for sludge management and treatment from the perspective of life cycle analysis, with special emphasis on those options that reduce environmental impacts and economic costs. Two pre-treatments (chemical or thermal) and two post-treatments (composting unit followed by land application or incineration) were evaluated to improve the eco-balance of the anaerobic digestion (AD) process in terms of operational (biogas production and digested sludge), environmental and economic indicators. According to the results obtained, both sludge pre-treatment alternatives proved to be an adequate alternative to improve biogas production without negatively affecting environmental and economic impacts. Finally, if the final disposal of the digestate is analysed, its application to the soil as a biofertiliser is recommended, since it presents a better environmental profile than incineration.
•Sludge pre-treatments present a good environmental profile when are included in a sludge line.•The incorporation of sludge pre-treatments does not increase significantly operational costs.•Pre-treatments increase biogas production which implies more eco-efficient wastewater systems.•Payback time is reduced in the plants that incorporate a sludge pre-treatment.
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