Jejunal gene expression patterns correlate with severity of systemic infection in chicken

<p>Abstract</p> <p>Background</p> <p>Not much is known about the effect of <it>Salmonella enteritidis</it> on changes in the developmental processes occurring in the intestine of young chicken. Therefore we investigated the correlation of intestinal gene expression patterns with the severity of systemic Salmonella infections.</p> <p>Methods</p> <p>The number of Salmonella colony forming units (CFUs) in the liver of infected chicken were plotted against the average intestinal expression profiles of previously identified gene expression clusters. The functional properties of all the genes taken together present in 3 clusters exhibiting positive correlation at early time-points were compared with the functional properties of the genes displaying antagonistic correlations in 1 cluster. The top 5 ranking functional groups were analysed in further detail.</p> <p>Results</p> <p>Three clusters showed gene expression profiles which were positively correlated with the severity of systemic disease as measured by the number of Salmonella colony forming units in the liver. In these clusters, genes involved in morphological processes were predominantly present. One cluster had a profile that was negatively correlated with the severity of systemic disease, as measured by numbers of CFUs in the liver. The genes in the latter cluster were mostly involved in cell turn-over and metabolism.</p> <p>Conclusions</p> <p>In the developing jejunum of young chicken, both stimulatory and inhibitory gene expression mechanisms are correlated with the severity of systemic Salmonella infections.</p

MASTL promotes cell contractility and motility through kinase-independent signaling

Microtubule-associated serine/threonine-protein kinase-like (MASTL) is a mitosis-accelerating kinase with emerging roles in cancer progression. However, possible cell cycle-independent mechanisms behind its oncogenicity remain ambiguous. Here, we identify MASTL as an activator of cell contractility and MRTF-A/SRF (myocardin-related transcription factor A/serum response factor) signaling. Depletion of MASTL increased cell spreading while reducing contractile actin stress fibers in normal and breast cancer cells and strongly impairing breast cancer cell motility and invasion. Transcriptome and proteome profiling revealed MASTL-regulated genes implicated in cell movement and actomyosin contraction, including Rho guanine nucleotide exchange factor 2 (GEF-H1, ARHGEF2) and MRTF-A target genes tropomyosin 4.2 (TPM4), vinculin (VCL), and nonmuscle myosin IIB (NM-2B, MYH10). Mechanistically, MASTL associated with MRTF-A and increased its nuclear retention and transcriptional activity. Importantly, MASTL kinase activity was not required for regulation of cell spreading or MRTF-A/SRF transcriptional activity. Taken together, we present a previously unknown kinase-independent role for MASTL as a regulator of cell adhesion, contractility, and MRTF-A/SRF activity. [Abstract copyright: © 2020 Taskinen et al.

Teriflunomide treatment for multiple sclerosis modulates T cell mitochondrial respiration with affinity-dependent effects

International audienceInterference with immune cell proliferation represents a successful treatment strategy in T cell-mediated autoimmune diseases such as rheumatoid arthritis and multiple sclerosis (MS). One prominent example is pharmacological inhibition of dihydroorotate dehydrogenase (DHODH), which mediates de novo pyrimidine synthesis in actively proliferating T and B lymphocytes. Within the TERIDYNAMIC clinical study, we observed that the DHODH inhibitor teriflunomide caused selective changes in T cell subset composition and T cell receptor repertoire diversity in patients with relapsing-remitting MS (RRMS). In a preclinical antigen-specific setup, DHODH inhibition preferentially suppressed the proliferation of high-affinity T cells. Mechanistically, DHODH inhibition interferes with oxidative phosphorylation (OXPHOS) and aerobic glycolysis in activated T cells via functional inhibition of complex III of the respiratory chain. The affinity-dependent effects of DHODH inhibition were closely linked to differences in T cell metabolism. High-affinity T cells preferentially use OXPHOS during early activation, which explains their increased susceptibility toward DHODH inhibition. In a mouse model of MS, DHODH inhibitory treatment resulted in preferential inhibition of high-affinity autoreactive T cell clones. Compared to T cells from healthy controls, T cells from patients with RRMS exhibited increased OXPHOS and glycolysis, which were reduced with teriflunomide treatment. Together, these data point to a mechanism of action where DHODH inhibition corrects metabolic disturbances in T cells, which primarily affects profoundly metabolically active high-affinity T cell clones. Hence, DHODH inhibition may promote recovery of an altered T cell receptor repertoire in autoimmunity

A robust measure of correlation between two genes on a microarray

<p>Abstract</p> <p>Background</p> <p>The underlying goal of microarray experiments is to identify gene expression patterns across different experimental conditions. Genes that are contained in a particular pathway or that respond similarly to experimental conditions could be co-expressed and show similar patterns of expression on a microarray. Using any of a variety of clustering methods or gene network analyses we can partition genes of interest into groups, clusters, or modules based on measures of similarity. Typically, Pearson correlation is used to measure distance (or similarity) before implementing a clustering algorithm. Pearson correlation is quite susceptible to outliers, however, an unfortunate characteristic when dealing with microarray data (well known to be typically quite noisy.)</p> <p>Results</p> <p>We propose a resistant similarity metric based on Tukey's biweight estimate of multivariate scale and location. The resistant metric is simply the correlation obtained from a resistant covariance matrix of scale. We give results which demonstrate that our correlation metric is much more resistant than the Pearson correlation while being more efficient than other nonparametric measures of correlation (e.g., Spearman correlation.) Additionally, our method gives a systematic gene flagging procedure which is useful when dealing with large amounts of noisy data.</p> <p>Conclusion</p> <p>When dealing with microarray data, which are known to be quite noisy, robust methods should be used. Specifically, robust distances, including the biweight correlation, should be used in clustering and gene network analysis.</p

Large expert-curated database for benchmarking document similarity detection in biomedical literature search

Document recommendation systems for locating relevant literature have mostly relied on methods developed a decade ago. This is largely due to the lack of a large offline gold-standard benchmark of relevant documents that cover a variety of research fields such that newly developed literature search techniques can be compared, improved and translated into practice. To overcome this bottleneck, we have established the RElevant LIterature SearcH consortium consisting of more than 1500 scientists from 84 countries, who have collectively annotated the relevance of over 180 000 PubMed-listed articles with regard to their respective seed (input) article/s. The majority of annotations were contributed by highly experienced, original authors of the seed articles. The collected data cover 76% of all unique PubMed Medical Subject Headings descriptors. No systematic biases were observed across different experience levels, research fields or time spent on annotations. More importantly, annotations of the same document pairs contributed by different scientists were highly concordant. We further show that the three representative baseline methods used to generate recommended articles for evaluation (Okapi Best Matching 25, Term Frequency-Inverse Document Frequency and PubMed Related Articles) had similar overall performances. Additionally, we found that these methods each tend to produce distinct collections of recommended articles, suggesting that a hybrid method may be required to completely capture all relevant articles. The established database server located at https://relishdb.ict.griffith.edu.au is freely available for the downloading of annotation data and the blind testing of new methods. We expect that this benchmark will be useful for stimulating the development of new powerful techniques for title and title/abstract-based search engines for relevant articles in biomedical research.Peer reviewe

The use of Matti : a tangible user interface in physical rehabilitation to motivate children and older adults

Abstract: Highly motivated patients who enjoy their physical rehabilitation tend to attain better therapeutic outcomes. However, given the prolonged repetitive nature of postural control rehabilitation in older adults and children with developmental coordination disorder (DCD), motivation levels might drop quickly. Exergames and digital therapy tools could offer practical answers to this issue and allow therapists to provide patients objective outcome measurements. To incorporate digital innovation in clinical and rehabilitation practices, this study discusses Matti, an interactive system created as a customisable tangible user interface (TUI). Its usability in pediatric and geriatric physiotherapy contexts is explored and evaluated through user evaluation. The Matti device was found to be usable and enjoyable for exergaming rehabilitation. However, additional study on measuring capabilities is needed to enable the accurate and reliable objective outcome measurements through this TUI. Future research should analyse how this TUI and gamified postural control assessment affects patients' motivation and therapeutic outcomes

Aspects of Radiocarbon Determinations and the Dating of the Transition from The Chalcolithic Period to Early Bronze Age I in the Southern Levant

Although a chrono-cultural sequence, including a Chalcolithic period followed by an Early Bronze Age has long been accepted for the Southern Levant, relatively little was understood of the transition between those two distinct entities. Recent discoveries, particularly in the area of the western piedmont of the Judea-Samaria incline (the Shephela), have yielded substantial evidence of continuity in occupation and thus, the nature of the transition for that region and its relationship to the greater Southern Levant. This paper examines the radiocarbon evidence from the site of Modi’in in the Shephela, which indicates the transition there to have occurred in the fi rst half of the 4th millennium BC. Using Bayesian analyses of the data, it further considers additional radiocarbon dates from other sites in the greater region, while offering a practical guide for evaluating validity of individual data to date archaeological deposits to which they have been ascribed.Bien qu’une séquence chrono-culturelle comprenant une période chalcolitique suivie d’un Bronze ancien ait été depuis longtemps établie pour le sud Levant, la transition entre ces deux périodes demeure mal comprise. Des découvertes récentes, en particulier dans le piémont occidental de Judée-Samarie, la Shéphéla, témoignent d’une occupation continue. Elles fournissent des informations importantes sur la nature de cette transition et sur les liens entre la Shéphéla et le reste du sud du Levant. Les résultats obtenus par le radiocarbone à partir des vestiges provenant du site de Modi’in dans la région de la Shéphéla sont examinés. Ils permettent de dater la transition entre le Chalcolithique et le Bronze ancien de la première moitié du IVe millénaire avant notre ère. En utilisant la méthode bayésienne, ces données sont ensuite incorporées dans un ensemble interrégional de datations. Cette approche permet une meilleure évaluation des dates d’occupation des sites considérés et de la séquence de la transition, tout en offrant un guide pratique permettant d’estimer la place chronologique des vestiges archéologiques.Braun Eliot, Van den Brink Edwin C. M., Regev Johanna, Boaretto Elisabetta, Bar Shay. Aspects of Radiocarbon Determinations and the Dating of the Transition from The Chalcolithic Period to Early Bronze Age I in the Southern Levant. In: Paléorient, 2013, vol. 39, n°1. The Transition Late Chalcolithic to Early Bronze Age in the Southern Levant. pp. 23-46