Cellular population dynamics control the robustness of the stem cell niche.

Within populations of cells, fate decisions are controlled by an indeterminate combination of cell-intrinsic and cell-extrinsic factors. In the case of stem cells, the stem cell niche is believed to maintain 'stemness' through communication and interactions between the stem cells and one or more other cell-types that contribute to the niche conditions. To investigate the robustness of cell fate decisions in the stem cell hierarchy and the role that the niche plays, we introduce simple mathematical models of stem and progenitor cells, their progeny and their interplay in the niche. These models capture the fundamental processes of proliferation and differentiation and allow us to consider alternative possibilities regarding how niche-mediated signalling feedback regulates the niche dynamics. Generalised stability analysis of these stem cell niche systems enables us to describe the stability properties of each model. We find that although the number of feasible states depends on the model, their probabilities of stability in general do not: stem cell-niche models are stable across a wide range of parameters. We demonstrate that niche-mediated feedback increases the number of stable steady states, and show how distinct cell states have distinct branching characteristics. The ecological feedback and interactions mediated by the stem cell niche thus lend (surprisingly) high levels of robustness to the stem and progenitor cell population dynamics. Furthermore, cell-cell interactions are sufficient for populations of stem cells and their progeny to achieve stability and maintain homeostasis. We show that the robustness of the niche - and hence of the stem cell pool in the niche - depends only weakly, if at all, on the complexity of the niche make-up: simple as well as complicated niche systems are capable of supporting robust and stable stem cell dynamics

Relationship of literacy and heart failure in adults with diabetes

<p>Abstract</p> <p>Background</p> <p>Although reading ability may impact educational strategies and management of heart failure (HF), the prevalence of limited literacy in patients with HF is unknown.</p> <p>Methods</p> <p>Subjects were drawn from the Vermont Diabetes Information System Field Survey, a cross-sectional study of adults with diabetes in primary care. Participants' self-reported characteristics were subjected to logistic regression to estimate the association of heart failure and literacy while controlling for social and economic factors. The Short Test of Functional Health Literacy was used to measure literacy.</p> <p>Results</p> <p>Of 172 subjects with HF and diabetes, 27% had limited literacy compared to 15% of 826 subjects without HF (OR 2.05; 95% CI 1.39, 3.02; <it>P </it>< 0.001). Adjusting for age, sex, race, income, marital status and health insurance, HF continued to be significantly associated with limited literacy (OR 1.55, 95% CI 1.00, 2.41, <it>P </it>= .05).</p> <p>After adjusting for education, however, HF was no longer independently associated with literacy (OR 1.31; 95% CI 0.82 – 2.08; <it>P </it>= 0.26).</p> <p>Conclusion</p> <p>Over one quarter of diabetic adults with HF have limited literacy. Although this association is no longer statistically significant when adjusted for education, clinicians should be aware that many of their patients have important limitations in dealing with written materials.</p

Intra-cluster correlation coefficients in adults with diabetes in primary care practices: the Vermont Diabetes Information System field survey

BACKGROUND: Proper estimation of sample size requirements for cluster-based studies requires estimates of the intra-cluster correlation coefficient (ICC) for the variables of interest. METHODS: We calculated the ICC for 112 variables measured as part of the Vermont Diabetes Information System, a cluster-randomized study of adults with diabetes from 73 primary care practices (the clusters) in Vermont and surrounding areas. RESULTS: ICCs varied widely around a median value of 0.0185 (Inter-quartile range: 0.006, 0.037). Some characteristics (such as the proportion having a recent creatinine measurement) were highly associated with the practice (ICC = 0.288), while others (prevalence of some comorbidities and complications and certain aspects of quality of life) varied much more across patients with only small correlation within practices (ICC<0.001). CONCLUSION: The ICC values reported here may be useful in designing future studies that use clustered sampling from primary care practices

Bacterial adaptation is constrained in complex communities

© 2020, The Author(s). A major unresolved question is how bacteria living in complex communities respond to environmental changes. In communities, biotic interactions may either facilitate or constrain evolution depending on whether the interactions expand or contract the range of ecological opportunities. A fundamental challenge is to understand how the surrounding biotic community modifies evolutionary trajectories as species adapt to novel environmental conditions. Here we show that community context can dramatically alter evolutionary dynamics using a novel approach that ‘cages’ individual focal strains within complex communities. We find that evolution of focal bacterial strains depends on properties both of the focal strain and of the surrounding community. In particular, there is a stronger evolutionary response in low-diversity communities, and when the focal species have a larger genome and are initially poorly adapted. We see how community context affects resource usage and detect genetic changes involved in carbon metabolism and inter-specific interaction. The findings demonstrate that adaptation to new environmental conditions should be investigated in the context of interspecific interactions

Read Length and Repeat Resolution: Exploring Prokaryote Genomes Using Next-Generation Sequencing Technologies

Background: There are a growing number of next-generation sequencing technologies. At present, the most cost-effective options also produce the shortest reads. However, even for prokaryotes, there is uncertainty concerning the utility of these technologies for the de novo assembly of complete genomes. This reflects an expectation that short reads will be unable to resolve small, but presumably abundant, repeats. Methodology/Principal Findings: Using a simple model of repeat assembly, we develop and test a technique that, for any read length, can estimate the occurrence of unresolvable repeats in a genome, and thus predict the number of gaps that would need to be closed to produce a complete sequence. We apply this technique to 818 prokaryote genome sequences. This provides a quantitative assessment of the relative performance of various lengths. Notably, unpaired reads of only 150nt can reconstruct approximately 50 % of the analysed genomes with fewer than 96 repeat-induced gaps. Nonetheless, there is considerable variation amongst prokaryotes. Some genomes can be assembled to near contiguity using very short reads while others require much longer reads. Conclusions: Given the diversity of prokaryote genomes, a sequencing strategy should be tailored to the organism unde

The role of endothelin-1 in hyperoxia-induced lung injury in mice

BACKGROUND: As prolonged hyperoxia induces extensive lung tissue damage, we set out to investigate the involvement of endothelin-1 (ET-1) receptors in these adverse changes. METHODS: Experiments were performed on four groups of mice: control animals kept in room air and a group of mice exposed to hyperoxia for 60 h were not subjected to ET-1 receptor blockade, whereas the dual ETA/ETB-receptor blocker tezosantan (TEZ) was administered via an intraperitoneal pump (10 mg/kg/day for 6 days) to other groups of normal and hyperoxic mice. The respiratory system impedance (Zrs) was measured by means of forced oscillations in the anesthetized, paralyzed and mechanically ventilated mice before and after the iv injection of ET-1 (2 μg). Changes in the airway resistance (Raw) and in the tissue damping (G) and elastance (H) of a constant-phase tissue compartment were identified from Zrs by model fitting. RESULTS: The plasma ET-1 level increased in the mice exposed to hyperoxia (3.3 ± 1.6 pg/ml) relative to those exposed to room air (1.6 ± 0.3 pg/ml, p < 0.05). TEZ administration prevented the hyperoxia-induced increases in G (13.1 ± 1.7 vs. 9.6 ± 0.3 cmH(2)O/l, p < 0.05) and H (59 ± 9 vs. 41 ± 5 cmH(2)O/l, p < 0.05) and inhibited the lung responses to ET-1. Hyperoxia decreased the reactivity of the airways to ET-1, whereas it elevated the reactivity of the tissues. CONCLUSION: These findings substantiate the involvement of the ET-1 receptors in the physiopathogenesis of hyperoxia-induced lung damage. Dual ET-1 receptor antagonism may well be of value in the prevention of hyperoxia-induced parenchymal damage

Can computerized clinical decision support systems improve practitioners' diagnostic test ordering behavior? A decision-maker-researcher partnership systematic review

<p>Abstract</p> <p>Background</p> <p>Underuse and overuse of diagnostic tests have important implications for health outcomes and costs. Decision support technology purports to optimize the use of diagnostic tests in clinical practice. The objective of this review was to assess whether computerized clinical decision support systems (CCDSSs) are effective at improving ordering of tests for diagnosis, monitoring of disease, or monitoring of treatment. The outcome of interest was effect on the diagnostic test-ordering behavior of practitioners.</p> <p>Methods</p> <p>We conducted a decision-maker-researcher partnership systematic review. We searched MEDLINE, EMBASE, Ovid's EBM Reviews database, Inspec, and reference lists for eligible articles published up to January 2010. We included randomized controlled trials comparing the use of CCDSSs to usual practice or non-CCDSS controls in clinical care settings. Trials were eligible if at least one component of the CCDSS gave suggestions for ordering or performing a diagnostic procedure. We considered studies 'positive' if they showed a statistically significant improvement in at least 50% of test ordering outcomes.</p> <p>Results</p> <p>Thirty-five studies were identified, with significantly higher methodological quality in those published after the year 2000 (<it>p </it>= 0.002). Thirty-three trials reported evaluable data on diagnostic test ordering, and 55% (18/33) of CCDSSs improved testing behavior overall, including 83% (5/6) for diagnosis, 63% (5/8) for treatment monitoring, 35% (6/17) for disease monitoring, and 100% (3/3) for other purposes. Four of the systems explicitly attempted to reduce test ordering rates and all succeeded. Factors of particular interest to decision makers include costs, user satisfaction, and impact on workflow but were rarely investigated or reported.</p> <p>Conclusions</p> <p>Some CCDSSs can modify practitioner test-ordering behavior. To better inform development and implementation efforts, studies should describe in more detail potentially important factors such as system design, user interface, local context, implementation strategy, and evaluate impact on user satisfaction and workflow, costs, and unintended consequences.</p

Classification and nomenclature of all human homeobox genes

<p>Abstract</p> <p>Background</p> <p>The homeobox genes are a large and diverse group of genes, many of which play important roles in the embryonic development of animals. Increasingly, homeobox genes are being compared between genomes in an attempt to understand the evolution of animal development. Despite their importance, the full diversity of human homeobox genes has not previously been described.</p> <p>Results</p> <p>We have identified all homeobox genes and pseudogenes in the euchromatic regions of the human genome, finding many unannotated, incorrectly annotated, unnamed, misnamed or misclassified genes and pseudogenes. We describe 300 human homeobox loci, which we divide into 235 probable functional genes and 65 probable pseudogenes. These totals include 3 genes with partial homeoboxes and 13 pseudogenes that lack homeoboxes but are clearly derived from homeobox genes. These figures exclude the repetitive <it>DUX1 </it>to <it>DUX5 </it>homeobox sequences of which we identified 35 probable pseudogenes, with many more expected in heterochromatic regions. Nomenclature is established for approximately 40 formerly unnamed loci, reflecting their evolutionary relationships to other loci in human and other species, and nomenclature revisions are proposed for around 30 other loci. We use a classification that recognizes 11 homeobox gene 'classes' subdivided into 102 homeobox gene 'families'.</p> <p>Conclusion</p> <p>We have conducted a comprehensive survey of homeobox genes and pseudogenes in the human genome, described many new loci, and revised the classification and nomenclature of homeobox genes. The classification scheme may be widely applicable to homeobox genes in other animal genomes and will facilitate comparative genomics of this important gene superclass.</p

Synchronization of cytoplasmic and transferred mitochondrial ribosomal protein gene expression in land plants is linked to Telo-box motif enrichment

<p>Abstract</p> <p>Background</p> <p>Chloroplasts and mitochondria evolved from the endosymbionts of once free-living eubacteria, and they transferred most of their genes to the host nuclear genome during evolution. The mechanisms used by plants to coordinate the expression of such transferred genes, as well as other genes in the host nuclear genome, are still poorly understood.</p> <p>Results</p> <p>In this paper, we use nuclear-encoded chloroplast (cpRPGs), as well as mitochondrial (mtRPGs) and cytoplasmic (euRPGs) ribosomal protein genes to study the coordination of gene expression between organelles and the host. Results show that the mtRPGs, but not the cpRPGs, exhibit strongly synchronized expression with euRPGs in all investigated land plants and that this phenomenon is linked to the presence of a <it>telo</it>-box DNA motif in the promoter regions of mtRPGs and euRPGs. This motif is also enriched in the promoter regions of genes involved in DNA replication. Sequence analysis further indicates that mtRPGs, in contrast to cpRPGs, acquired <it>telo</it>-box from the host nuclear genome.</p> <p>Conclusions</p> <p>Based on our results, we propose a model of plant nuclear genome evolution where coordination of activities in mitochondria and chloroplast and other cellular functions, including cell cycle, might have served as a strong selection pressure for the differential acquisition of <it>telo</it>-box between mtRPGs and cpRPGs. This research also highlights the significance of physiological needs in shaping transcriptional regulatory evolution.</p

Measuring capacity building in communities: a review of the literature

<p>Abstract</p> <p>Background</p> <p>Although communities have long been exhorted to make efforts to enhance their own health, such approaches have often floundered and resulted in little or no health benefits when the capacity of the community has not been adequately strengthened. Thus being able to assess the capacity building process is paramount in facilitating action in communities for social and health improvement. The current review aims to i) identify all domains used in systematically documented frameworks developed by other authors to assess community capacity building; and ii) to identify the dimensions and attributes of each of the domains as ascribed by these authors and reassemble them into a comprehensive compilation.</p> <p>Methods</p> <p>Relevant published articles were identified through systematic electronic searches of selected databases and the examination of the bibliographies of retrieved articles. Studies assessing capacity building or community development or community participation were selected and assessed for methodological quality, and quality in relation to the development and application of domains which were identified as constituents of community capacity building. Data extraction and analysis were undertaken using a realist synthesis approach.</p> <p>Results</p> <p>Eighteen articles met the criteria for this review. The various domains to assess community capacity building were identified and reassembled into nine comprehensive domains: "learning opportunities and skills development", "resource mobilization", "partnership/linkages/networking", "leadership", "participatory decision-making", "assets-based approach", "sense of community", "communication", and "development pathway". Six sub-domains were also identified: "shared vision and clear goals", "community needs assessment", "process and outcome monitoring", "sustainability", "commitment to action" and "dissemination".</p> <p>Conclusions</p> <p>The set of domains compiled in this review serve as a foundation for community-based work by those in the field seeking to support and nurture the development of competent communities. Further research is required to examine the robustness of capacity domains over time and to examine capacity development in association with health or other social outcomes.</p