Role of PINCH and Its Partner Tumor Suppressor Rsu-1 in Regulating Liver Size and Tumorigenesis

Particularly interesting new cysteine-histidine-rich protein (PINCH) protein is part of the ternary complex known as the IPP (integrin linked kinase (ILK)-PINCH-Parvin-α) complex. PINCH itself binds to ILK and to another protein known as Rsu-1 (Ras suppressor 1). We generated PINCH 1 and PINCH 2 Double knockout mice (referred as PINCH DKO mice). PINCH2 elimination was systemic whereas PINCH1 elimination was targeted to hepatocytes. The genetically modified mice were born normal. The mice were sacrificed at different ages after birth. Soon after birth, they developed abnormal hepatic histology characterized by disorderly hepatic plates, increased proliferation of hepatocytes and biliary cells and increased deposition of extracellular matrix. After a sustained and prolonged proliferation of all epithelial components, proliferation subsided and final liver weight by the end of 30 weeks in livers with PINCH DKO deficient hepatocytes was 40% larger than the control mice. The livers of the PINCH DKO mice were also very stiff due to increased ECM deposition throughout the liver, with no observed nodularity. Mice developed liver cancer by one year. These mice regenerated normally when subjected to 70% partial hepatectomy and did not show any termination defect. Ras suppressor 1 (Rsu-1) protein, the binding partner of PINCH is frequently deleted in human liver cancers. Rsu-1 expression is dramatically decreased in PINCH DKO mouse livers. Increased expression of Rsu-1 suppressed cell proliferation and migration in HCC cell lines. These changes were brought about not by affecting activation of Ras (as its name suggests) but by suppression of Ras downstream signaling via RhoGTPase proteins. In conclusion, our studies suggest that removal of PINCH results in enlargement of liver and tumorigenesis. Decreased levels of Rsu-1, a partner for PINCH and a protein often deleted in human liver cancer, may play an important role in the development of the observed phenotype. © 2013 Donthamsetty et al

Stakeholder engagement in hydro-climatic services in India: report of pump priming project April 2019

The India-UK Water Centre (IUKWC) promotes cooperation and collaboration between the complementary priorities of NERC-MoES water security research. This report presents an overview of a research project funded as a pump priming activity by the India-UK Water Centre (IUKWC), carried out between July–October 2017. Project activities included: a webinar, a desk-based literature review, a series of expert interviews and a participatory workshop held at the Indian Institute of Tropical Meteorology, Pune, in September 2017. The research was led by Dr Zareen Pervez Bharucha (Anglia Ruskin University), who worked with a team of scholars from the UK and India. This report outlines the key activities undertaken during the project, gives an overview of our research methods, and outlines the main findings. It is intended for participants in the research process, members of the India-UK Water Centre, and other stakeholders who have an interest in developing hydro-climatic services in India or comparable contexts. It should be read in conjunction with a State of the Science brief available on the IUKWC website (www.iukwc.org)

Random Regression for Modeling Semen Fertility in HF Purebred and Crossbred Bulls Using a Bayesian Framework

Data on insemination records of Holstein Friesian (HF) purebred (n=45,497) and crossbred (n=58,497) collected from the BAIF Research Foundation were utilized. The conception rate was modeled as a binary trait, using linear repeatability models. Random regression models (RRM) were used to obtain the trajectory of variance components across age of the bulls. Legendre Polynomials up to order of fit of 4 were used for the random effects of additive genetic and permanent environmental effects. 200,000 Gibbs samples were generated with a burn-in of 20,000 and thinning interval of 50 using the THRGIBBS1F90 program. Heritability estimates were very low (0.1) in both breeds but peaked at the extreme ages. Heritability and repeatability estimates ranged between 0.038 (8 years) to 0.627 (10 years) and 0.060 to 0.809 respectively in purebreds. Narrower ranges of 0.010 (4 years) to 0.087 (11 years) and 0.532 to 0.832 for heritability and repeatability respectively, were obtained in crossbreds. Effect of permanent environment was low in purebreds compared to the crossbreds. The study using RRM was able to provide genetic parameter estimates of fertility for all ages throughout the productive lifespan of bulls

Does commitment to rehabilitation influence clinical outcome of total hip resurfacing arthroplasty?

BACKGROUND: The purpose of this study was to evaluate whether compliance and rehabilitative efforts were predictors of early clinical outcome of total hip resurfacing arthroplasty. METHODS: A cross-sectional survey was utilized to collect information from 147 resurfacing patients, who were operated on by a single surgeon, regarding their level of commitment to rehabilitation following surgery. Patients were followed for a mean of 52 months (range, 24 to 90 months). Clinical outcomes and functional capabilities were assessed utilizing the Harris hip objective rating system, the SF-12 Health Survey, and an eleven-point satisfaction score. A linear regression analysis was used to determine whether there was any correlation between the rehabilitation commitment scores and any of the outcome measures, and a multivariate regression model was used to control for potentially confounding factors. RESULTS: Overall, an increased level of commitment to rehabilitation was positively correlated with each of the following outcome measures: SF-12 Mental Component Score, SF-12 Physical Component Score, Harris Hip score, and satisfaction scores. These correlations remained statistically significant in the multivariate regression model. CONCLUSIONS: Patients who were more committed to their therapy after hip resurfacing returned to higher levels of functionality and were more satisfied following their surgery

Modelling particle mass and particle number emissions during the active regeneration of diesel particulate filters

A new model has been developed to describe the size-dependent effects that are responsible for transient particle mass (PM) and particle number (PN) emissions observed during experiments of the active regeneration of Diesel Particulate Filters (DPFs). The model uses a population balance approach to describe the size of the particles entering and leaving the DPF, and accumulated within it. The population balance is coupled to a unit collector model that describes the filtration of the particles in the porous walls of the DPF and a reactor network model that is used to describe the geometry of the DPF. Two versions of the unit collector model were investigated. The original version, based on current literature, and an extended version, developed in this work, that includes terms to describe both the non-uniform regeneration of the cake and thermal expansion of the pores in the DPF. Simulations using the original unit collector model were able to provide a good description of the pressure drop and PM filtration efficiency during the loading of the DPF, but were unable to adequately describe the change in filtration efficiency during regeneration of the DPF. The introduction of the extended unit collector description enabled the model to describe both the timing of particle breakthrough and the final steady filtration efficiency of the hot regenerated DPF. Further work is required to understand better the transient behaviour of the system. In particular, we stress the importance that future experiments fully characterise the particle size distribution at both the inlet and outlet of the DPF.Cambridge Centre for Advanced Research and Education in Singapore (CARES), Royal Dutch Shell. Note: need to add PEMS4NANO (H2020) and EPSRC