10 research outputs found
Characterizing features of Escherichia coli UTI89 inhibition by urinary Lactobacillus gasseri 5006-2
No full textThe urinary tract hosts a urobiome that may play a role in health and disease, such as in urinary tract infection. Lactic acid-producing bacteria, or lactobacilli, have been identified as defenders against pathogens in microbiome niches and are abundant in the female urobiome. Previous work has observed that urinary lactobacilli inhibit the growth of pathogenic strains in vitro, including the predominant uropathogenic Escherichia coli. The goal of this project was to characterize the features of these interactions as a first step in elucidating the mechanism(s) of inhibition. Liquid co-cultures of urinary isolates, Lactobacillus gasseri 5006-2, and model UPEC strain, UTI89, were used to model inhibition over time. Results indicate a complex and contact-dependent interaction that contradicts the traditional hypothesis of inhibition by acidic organic acids produced by lactobacilli. Characterizing these interactions is essential to a robust understanding of the role of the urobiome in susceptibility to urinary disease
Genistein-mediated diet tends to increase oxidative stress in the vasculature of female ob/ob mice
No full textabstract: Morbid obesity is associated with cardiovascular and metabolic disorders. A major contributor to the pathogenesis of these diseases is impaired vasodilation resulting from elevated reactive oxygen species (ROS). This is because certain ROS such as superoxide are raised with obesity and scavenge the endogenous vasorelaxant nitric oxide, resulting in hypertension. The objective of this study was to measure the ability of genistein to quench superoxide in the vasculature of ob/ob mice, an animal model of obesity and type 2 diabetes. Genistein is an isoflavonic phytoestrogen naturally found in soy products. While genistein has documented antioxidant and anti-inflammatory properties, it is not known whether this protects the vasculature from oxidative stress. Genistein was hypothesized to reduce superoxide in arteries from female ob/ob mice. The superoxide indicator dihydroethidium (DHE) [2µL/mL HEPES buffer] was added to isolated aortae and mesenteric arteries from mice fed either a control (standard rodent chow containing 200-300 mg genistein/kg) or genistein-enriched (600mg genistein/kg rodent chow) diets for 4 weeks. Frozen tissues sections were collected onto glass microscope slides and examined using confocal microscopy. Contrary to the hypothesis, a diet containing twice the amount of genistein found in standard chow did not significantly reduce superoxide concentrations in aortae (p=0.287) or mesenteric arteries (p=0.352). Superoxide dismutase, an antioxidant enzyme that breaks down superoxide, was significantly upregulated in the genistein-enriched diet group (p=0.004), although this elevation did not promote the breakdown of superoxide. In addition, the inflammatory marker iNOS was not downregulated in the genistein-enriched diet group (p>0.05). The results indicate that high amounts of isoflavones, like genistein, may not exhibit the purported antioxidant effects in the vasculature of obese or diabetic subjects. Further studies examining arteries from ob/ob mice fed a genistein-free diet are needed to elucidate the true effects of genistein on oxidative stress
Author Correction: Comprehensive analysis of chromothripsis in 2,658 human cancers using whole-genome sequencing
No full textauthor correctio
Preprinting is positively associated with early career researcher status in ecology and evolution
No full textThe usage of preprint servers in ecology and evolution is increasing, allowing research to be rapidly disseminated and available through open access at no cost. Early Career Researchers (ECRs) often have limited experience with the peer review process, which can be challenging when trying to build publication records and demonstrate research ability for funding opportunities, scholarships, grants, or faculty positions. ECRs face different challenges relative to researchers with permanent positions and established research programs. These challenges might also vary according to institution size and country, which are factors associated with the availability of funding for open access journals. We predicted that the career stage and institution size impact the relative usage of preprint servers among researchers in ecology and evolution. Using data collected from 500 articles (100 from each of two open access journals, two closed access journals, and a preprint server), we showed that ECRs generated more preprints relative to non-ECRs, for both first and last authors. We speculate that this pattern is reflective of the advantages of quick and open access research that is disproportionately beneficial to ECRs. There is also a marginal association between first author, institution size, and preprint usage, whereby the number of preprints tends to increase with institution size for ECRs. The United States and United Kingdom contributed the greatest number of preprints by ECRs, whereas non-Western countries contributed relatively fewer preprints. This empirical evidence that preprint usage varies with the career stage, institution size, and country helps to identify barriers surrounding large-scale adoption of preprinting in ecology and evolution
Author Correction: Pan-cancer analysis of whole genomes
No full textCell adhesion molecules are ubiquitous in multicellular organisms, specifying precise cell-cell interactions in processes as diverse as tissue development, immune cell trafficking and the wiring of the nervous system(1-4). Here we show that a wide array of synthetic cell adhesion molecules can be generated by combining orthogonal extracellular interactions with intracellular domains from native adhesion molecules, such as cadherins and integrins. The resulting molecules yield customized cell-cell interactions with adhesion properties that are similar to native interactions. The identity of the intracellular domain of the synthetic cell adhesion molecules specifies interface morphology and mechanics, whereas diverse homotypic or heterotypic extracellular interaction domains independently specify the connectivity between cells. This toolkit of orthogonal adhesion molecules enables the rationally programmed assembly of multicellular architectures, as well as systematic remodelling of native tissues. The modularity of synthetic cell adhesion molecules provides fundamental insights into how distinct classes of cell-cell interfaces may have evolved. Overall, these tools offer powerful abilities for cell and tissue engineering and for systematically studying multicellular organization. Synthetic cell adhesion molecules yield customized cell-cell interactions with adhesion properties that are similar to native interactions, and offer abilities for cell and tissue engineering and for systematically studying multicellular organization
A review of methods and data to determine raw material criticality
No full textThe assessment of the criticality of raw materials allows the identification of the likelihood of a supply disruption of a material and the vulnerability of a system (e.g. a national economy, technology, or company) to this disruption. Inconclusive outcomes of various studies suggest that criticality assessments would benefit from the identification of best practices. To prepare the field for such guidance, this paper aims to clarify the mechanisms that affect methodological choices which influence the results of a study. This is achieved via literature review and round table discussions among international experts. The paper demonstrates that criticality studies are divergent in the system under study, the anticipated risk, the purpose of the study, and material selection. These differences in goal and scope naturally result in different choices regarding indicator selection, the required level of aggregation as well as the subsequent choice of aggregation method, and the need for a threshold value. However, this link is often weak, which suggests a lack of understanding of cause-and-effect mechanisms of indicators and outcomes. Data availability is a key factor that limits the evaluation of criticality. Furthermore, data quality, including both data uncertainty and data representativeness, is rarely addressed in the interpretation and communication of results. Clear guidance in the formulation of goals and scopes of criticality studies, the selection of adequate indicators and aggregation methods, and the interpretation of the outcomes, are important initial steps in improving the quality of criticality assessments
Author Correction: Retrospective evaluation of whole exome and genome mutation calls in 746 cancer samples
No full text: Correction to this paper has been published: https://doi.org/10.1038/s41467-020-20128-w
Pan-cancer analysis of whole genomes
No full textCancer is driven by genetic change, and the advent of massively parallel sequencing has enabled systematic documentation of this variation at the whole-genome scale1,2,3. Here we report the integrative analysis of 2,658 whole-cancer genomes and their matching normal tissues across 38 tumour types from the Pan-Cancer Analysis of Whole Genomes (PCAWG) Consortium of the International Cancer Genome Consortium (ICGC) and The Cancer Genome Atlas (TCGA). We describe the generation of the PCAWG resource, facilitated by international data sharing using compute clouds. On average, cancer genomes contained 4–5 driver mutations when combining coding and non-coding genomic elements; however, in around 5% of cases no drivers were identified, suggesting that cancer driver discovery is not yet complete. Chromothripsis, in which many clustered structural variants arise in a single catastrophic event, is frequently an early event in tumour evolution; in acral melanoma, for example, these events precede most somatic point mutations and affect several cancer-associated genes simultaneously. Cancers with abnormal telomere maintenance often originate from tissues with low replicative activity and show several mechanisms of preventing telomere attrition to critical levels. Common and rare germline variants affect patterns of somatic mutation, including point mutations, structural variants and somatic retrotransposition. A collection of papers from the PCAWG Consortium describes non-coding mutations that drive cancer beyond those in the TERT promoter4; identifies new signatures of mutational processes that cause base substitutions, small insertions and deletions and structural variation5,6; analyses timings and patterns of tumour evolution7; describes the diverse transcriptional consequences of somatic mutation on splicing, expression levels, fusion genes and promoter activity8,9; and evaluates a range of more-specialized features of cancer genomes8,10,11,12,13,14,15,16,17,18
