\u3ci\u3eAkkermansia muciniphila\u3c/i\u3e and its membrane protein ameliorates intestinal inflammatory stress and promotes epithelial wound healing via CREBH and miR‑143/145

Background The intestinal epithelial barrier is the interface for interaction between gut microbiota and host metabolic systems. Akkermansia muciniphila (A. muciniphila) is a key player in the colonic microbiota that resides in the mucus layer, whose abundance is selectively decreased in the faecal microbiota of inflammatory bowel disease (IBD) patients. This study aims to investigate the regulatory mechanism among A. muciniphila, a transcription factor cAMPresponsive element-binding protein H (CREBH), and microRNA-143/145 (miR-143/145) in intestinal inflammatory stress, gut barrier integrity and epithelial regeneration. Methods A novel mouse model with increased colonization of A muciniphila in the intestine of CREBH knockout mice, an epithelial wound healing assay and several molecular biological techniques were applied in this study. Results were analysed using a homoscedastic 2-tailed t-test. Results Increased colonization of A. muciniphila in mouse gut enhanced expression of intestinal CREBH, which was associated with the mitigation of intestinal endoplasmic reticulum (ER) stress, gut barrier leakage and blood endotoxemia induced by dextran sulfate sodium (DSS). Genetic depletion of CREBH (CREBH-KO) significantly inhibited the expression of tight junction proteins that are associated with gut barrier integrity, including Claudin5 and Claudin8, but upregulated Claudin2, a tight junction protein that enhances gut permeability, resulting in intestinal hyperpermeability and inflammation. Upregulation of CREBH by A. muciniphila further coupled with miR-143/145 promoted intestinal epithelial cell (IEC) regeneration and wound repair via insulin-like growth factor (IGF) and IGFBP5 signalling. Moreover, the gene expressing an outer membrane protein of A. muciniphila, Amuc_1100, was cloned into a mammalian cell-expression vector and successfully expressed in porcine and human IECs. Expression of Amuc_1100 in IECs could recapitulate the health beneficial effect of A. muciniphila on the gut by activating CREBH, inhibiting ER stress and enhancing the expression of genes involved in gut barrier integrity and IEC’s regeneration. Conclusions This study uncovers a novel mechanism that links A. muciniphila and its membrane protein with host CREBH, IGF signalling and miRNAs in mitigating intestinal inflammatory stress–gut barrier permeability and promoting intestinal wound healing. This novel finding may lend support to the development of therapeutic approaches for IBD by manipulating the interaction between host genes, gut bacteria and its bioactive components

Vaccine for hypertension: Modulating the renin-angiotensin system

Abstract Hypertension, which is one of the most common diseases afflicting mankind, is associated to increased morbidity, mortality and cost to society. Cardiovascular disease is the leading cause of death all around the world and hypertension is the most common reversible risk factor for cardiovascular diseases. The renin-angiotensin system (RAS) commands an important role in the regulation of blood pressure, and so, at present, has been a target for clinical control by drugs acting on the system. Despite the fact that effective drugs are available, only about one out of three people has their blood pressure successfully controlled, and the blame goes to the undesirable side effects and the poor oral drug compliance. Keeping in mind the increasing incidence of hypertension and the patients' inconsistency for the polypharmacy, immunization against renin and the angiotensins, although with less success, had been attempted in the past. More recently, immunization against angiotensin-I with PMD-3117 vaccine, angiotensin-II with CYT006-AngQb vaccine and targeting angiotensin-II type 1A receptor with ATR12181 vaccine have provided optimism in the development of a hypertension vaccine. AngQb vaccine has proved to become the first vaccine ever to lower (−9/−4 mm Hg) blood pressure in human beings. Vaccine could induce long lasting effects with a dosing interval of months, increasing patient acceptability and compliance and thus a better control of high blood pressure. Our objective will be to focus on the importance of the RAS and to explore the extent of safety, efficacy and the future implications of vaccine against the RAS

Automatic and fast segmentation of breast region-of-interest (ROI) and density in MRIs

Accurate segmentation of the breast region of interest (BROI) and breast density (BD) is a significant challenge during the analysis of breast MR images. Most of the existing methods for breast segmentation are semi-automatic and limited in their ability to achieve accurate results. This is because of difficulties in removing landmarks from noisy magnetic resonance images (MRI) due to similar intensity levels and the close connection to BROI. This study proposes an innovative, fully automatic and fast segmentation approach to identify and remove landmarks such as the heart and pectoral muscles. The BROI segmentation is carried out with a framework consisting of three major steps. Firstly, we use adaptive wiener filtering and k-means clustering to minimize the influence of noises, preserve edges and remove unwanted artefacts. The second step systematically excludes the heart area by utilizing active contour based level sets where initial contour points are determined by the maximum entropy thresholding and convolution method. Finally, a pectoral muscle is removed by using morphological operations and local adaptive thresholding on MR images. Prior to the elimination of the pectoral muscle, the MR image is sub divided into three sections: left, right, and central based on the geometrical information. Subsequently, a BD segmentation is achieved with 4 level fuzzy c-means (FCM) thresholding on the denoised BROI segmentation. The proposed method is validated using the 1350 breast images from 15 female subjects. The pixel-based quantitative analysis showed excellent segmentation results when compared with manually drawn BROI and BD. Furthermore, the presented results in terms of evaluation matrices: Acc, Sp, AUC, MR, P, Se and DSC demonstrate the high quality of segmentations using the proposed method. The average computational time for the segmentation of BROI and BD is 1 minute and 50 seconds

Optimizing Peri-URban Ecosystems (PURE) to re-couple urban-rural symbiosis

Globally, rapid urbanization, along with economic development, is dramatically changing the balance of biogeochemical cycles, impacting upon ecosystem services and impinging on United Nation global sustainability goals (inter alia: sustainable cities and communities; responsible consumption and production; good health and well-being; clean water and sanitation, and; to protect and conserve life on land and below water). A key feature of the urban ecosystems is that nutrient stocks, carbon (C), nitrogen (N) and phosphorus (P), are being enriched. Furthermore, urban ecosystems are highly engineered, biogeochemical cycling of nutrients within urban ecosystems is spatially segregated, and nutrients exported (e.g. in food) from rural/peri-urban areas are not being returned to support primary production in these environments. To redress these imbalances we propose the concept of the Peri-URban Ecosystem (PURE). Through the merging of conceptual approaches that relate to Critical Zone science and the dynamics of successional climax PURE serves at the symbiotic interface between rural/natural and urban ecosystems and allow re-coupling of resource flows. PURE provides a framework for tackling the most pressing of societal challenges and supporting global sustainability goals

Density Changes in Low Pressure Gas Targets for Electron Scattering Experiments

A system of modular sealed gas target cells has been developed for use in electron scattering experiments at the Thomas Jefferson National Accelerator Facility (Jefferson Lab). This system was initially developed to complete the MARATHON experiment which required, among other species, tritium as a target material. Thus far, the cells have been loaded with the gas species 3H, 3He, 2H, 1H and 40Ar and operated in nominal beam currents of up to 22.5 uA in Jefferson Lab's Hall A. While the gas density of the cells at the time of loading is known, the density of each gas varies uniquely when heated by the electron beam. To extract experimental cross sections using these cells, density dependence on beam current of each target fluid must be determined. In this study, data from measurements with several beam currents within the range of 2.5 to 22.5 uA on each target fluid are presented. Additionally, expressions for the beam current dependent fluid density of each target are developed.Comment: 8 pages, 12 figures, 4 table

Prognostic significance of the expression of GFRα1, GFRα3 and Syndecan-3, Proteins binding ARTEMIN, In mammary carcinoma

10.1186/1471-2407-13-34BMC Cancer13-BCMA

HLJ1 is a novel caspase-3 substrate and its expression enhances UV-induced apoptosis in non-small cell lung carcinoma

Carcinogenesis is determined based on both cell proliferation and death rates. Recent studies demonstrate that heat shock proteins (HSPs) regulate apoptosis. HLJ1, a member of the DnaJ-like Hsp40 family, is a newly identified tumor suppressor protein closely related to relapse and survival in non-small cell lung cancer (NSCLC) patients. However, its role in apoptosis is currently unknown. In this study, NSCLC cell lines displaying varying HLJ1 expression levels were subjected to ultraviolet (UV) irradiation, followed by flow cytometry. Interestingly, the percentages of apoptotic cells in the seven cell lines examined were positively correlated with HLJ1 expression. Enforcing expression of HLJ1 in low-HLJ1 expressing highly invasive cells promoted UV-induced apoptosis through enhancing JNK and caspase-3 activation in NSCLC. Additionally, UV irradiation led to reduced levels of HLJ1 predominantly in apoptotic cells. The pan-caspase inhibitor, zVAD-fmk and caspase-3-specific inhibitor, DEVD-fmk, prevented UV-induced degradation of HLJ1 by the late stage of apoptosis. Further experiments revealed a non-typical caspase-3 cleavage site (MEID) at amino acid 125–128 of HLJ1. Our results collectively suggest that HLJ1 is a novel substrate of caspase-3 during the UV-induced apoptotic process

Control and Characterization of Individual Grains and Grain Boundaries in Graphene Grown by Chemical Vapor Deposition

The strong interest in graphene has motivated the scalable production of high quality graphene and graphene devices. Since large-scale graphene films synthesized to date are typically polycrystalline, it is important to characterize and control grain boundaries, generally believed to degrade graphene quality. Here we study single-crystal graphene grains synthesized by ambient CVD on polycrystalline Cu, and show how individual boundaries between coalescing grains affect graphene's electronic properties. The graphene grains show no definite epitaxial relationship with the Cu substrate, and can cross Cu grain boundaries. The edges of these grains are found to be predominantly parallel to zigzag directions. We show that grain boundaries give a significant Raman "D" peak, impede electrical transport, and induce prominent weak localization indicative of intervalley scattering in graphene. Finally, we demonstrate an approach using pre-patterned growth seeds to control graphene nucleation, opening a route towards scalable fabrication of single-crystal graphene devices without grain boundaries.Comment: New version with additional data. Accepted by Nature Material