The Complete Genome Sequence of Haloferax volcanii DS2, a Model Archaeon

a key model organism, not only for the study of halophilicity, but also for archaeal biology in general. DS2, the type strain of this species. The genome contains a main 2.848 Mb chromosome, three smaller chromosomes pHV1, 3, 4 (85, 438, 636 kb, respectively) and the pHV2 plasmid (6.4 kb).

Conversion of IBD patient clinical and demographic data to single numeric values for hierarchical clustering.

<p>Conversion of IBD patient clinical and demographic data to single numeric values for hierarchical clustering.</p

An informatics approach to correlating immune phenotpyes with weight loss or colitis in a T cell transfer mouse model of IBD.

<p>(A) Weight loss in FVB.<i>Rag1</i>^<i>-/-</i> mice (<i>n</i> = 9) injected with wild type naïve CD4⁺ T cells. Weights are shown relative to day 0 (pre-transfer baseline). Bold red trace shows mean weight loss for the group; green and blue traces show individual mice displaying mild or aggressive weight loss, respectively. Examples of disease severity index (DSI) calculations are shown in color-coded text. (B) Quantitative colitis scores (<i>n</i> = 9) from the same group of T cell-transferred FVB.<i>Rag1</i>^<i>-/-</i> mice shown in (A). H&E-stained colon tissues were scored blindly as in [<a href="http://www.plosone.org/article/info:doi/10.1371/journal.pone.0163305#pone.0163305.ref017" target="_blank">17</a>]; representative micrographs (at right) show mild (score of 1) and severe (score of 3) inflammation (20x magnification). Red horizontal bar indicates mean colitis scores for the group. (C) <i>Left</i>, 10-parameter FACS panel used for analyzing <i>ex vivo</i> expression of surface antigens on leukocytes isolated from spleen, mesenteric lymph nodes (MLN), and colon lamina propria (colon) of FVB.<i>Rag1</i>^<i>-/-</i> mice injected as in (A). <i>Right</i>, Gating strategy for surface FACS analysis; immune subsets used in downstream analysis are indicated by gates, text, and where appropriate, percentages. (D) <i>Left</i>, 11-parameter FACS panel used for analyzing <i>ex vivo</i> expression of intracellular transcription factors and cytokines in leukocytes isolated from T cell-transferred FVB.<i>Rag1</i>^<i>-/-</i> mice as above. <i>Right</i>, Gating strategy for intracellular FACS analysis; immune subsets used in downstream analysis are indicated by gates, text, and where appropriate, percentages. (E) Heat map showing hierarchical clustering of 7 disease endpoints and 57 immune phenotypes in T cell-transferred FVB.<i>Rag1</i>^<i>-/-</i> mice as above. Dendrograms (far left) show the clustering relationship between the mice based on all disease endpoints and immunophenotypes.</p

Demographic data of healthy volunteers and IBD patients analyzed in the study.

<p>Demographic data of healthy volunteers and IBD patients analyzed in the study.</p

Distribution of DNA methylation Index among ten tumor suppressor genes in cervical cancer cases and controls.

<p>a. Number of cases and controls per gene vary due to exhausted DNA and/or inability to generate pyrosequencing data</p><p>b. Summary statistics with a nonparametric Mann-Whitney test comparing cases and controls for each gene</p><p>Distribution of DNA methylation Index among ten tumor suppressor genes in cervical cancer cases and controls.</p

Demographics and clinical characteristics of women with invasive cervical cancer and frequency matched controls.

<p>a. Numbers may not add up to total due to missing data.</p><p>b. Differences between cases and controls determined using the Fisher exact Chi2 test or T-test.</p><p>Demographics and clinical characteristics of women with invasive cervical cancer and frequency matched controls.</p

The Xenobiotic Transporter Mdr1 Enforces T Cell Homeostasis in the Presence of Intestinal Bile Acids

CD4+ T cells are tightly regulated by microbiota in the intestine, but whether intestinal T cells interface with host-derived metabolites is less clear. Here, we show that CD4+ T effector (Teff) cells upregulated the xenobiotic transporter, Mdr1, in the ileum to maintain homeostasis in the presence of bile acids. Whereas wild-type Teff cells upregulated Mdr1 in the ileum, those lacking Mdr1 displayed mucosal dysfunction and induced Crohn’s disease-like ileitis following transfer into Rag1−/− hosts. Mdr1 mitigated oxidative stress and enforced homeostasis in Teff cells exposed to conjugated bile acids (CBAs), a class of liver-derived emulsifying agents that actively circulate through the ileal mucosa. Blocking ileal CBA reabsorption in transferred Rag1−/− mice restored Mdr1-deficient Teff cell homeostasis and attenuated ileitis. Further, a subset of ileal Crohn’s disease patients displayed MDR1 loss of function. Together, these results suggest that coordinated interaction between mucosal Teff cells and CBAs in the ileum regulate intestinal immune homeostasis. [Display omitted] •CD4+ effector T cells upregulate Mdr1 expression in the ileum•Mdr1 protects effector T cells in the ileum from bile-acid-driven oxidative stress•Bile acid sequestration restores Mdr1-deficient T cell homeostasis in the ileum•A subset of ileal Crohn’s disease patients display MDR1 loss of function The role of host-derived intestinal metabolites in mucosal immune regulation is poorly understood. Here, Cao et al. show that effector CD4+ T cells upregulate expression of the xenobiotic transporter, Mdr1, in the ileum to safeguard immune homeostasis, revealing an important immunologic consequence of ileal bile acid reabsorption

The Multiple Sclerosis Data Alliance Catalogue Enabling Web-Based Discovery of Metadata from Real-World Multiple Sclerosis Data Sources

Background: One of the major objectives of the Multiple Sclerosis Data Alliance (MSDA) is to enable better discovery of multiple sclerosis (MS) real-world data (RWD). Methods: We implemented the MSDA Catalogue, which is available worldwide. The current version of the MSDA Catalogue collects descriptive information on governance, purpose, inclusion criteria, procedures for data quality control, and how and which data are collected, including the use of e-health technologies and data on collection of COVID-19 variables. The current cataloguing procedure is performed in several manual steps, securing an effective catalogue. Results: Herein we summarize the status of the MSDA Catalogue as of January 6, 2021. To date, 38 data sources across five continents are included in the MSDA Catalogue. These data sources differ in purpose, maturity, and variables collected, but this landscaping effort shows that there is substantial alignment on some domains. The MSDA Catalogue shows that personal data and basic disease data are the most collected categories of variables, whereas data on fatigue measurements and cognition scales are the least collected in MS registries/cohorts. Conclusions: The Web-based MSDA Catalogue provides strategic overview and allows authorized end users to browse metadata profiles of data cohorts and data sources. There are many existing and arising RWD sources in MS. Detailed cataloguing of MS RWD is a first and useful step toward reducing the time needed to discover MS RWD sets and promoting collaboration. Int J MS Care. 2021;23:261-268