Concise Review: The Potential Use of Intestinal Stem Cells to Treat Patients With Intestinal Failure.

: Intestinal failure is a rare life-threatening condition that results in the inability to maintain normal growth and hydration status by enteral nutrition alone. Although parenteral nutrition and whole organ allogeneic transplantation have improved the survival of these patients, current therapies are associated with a high risk for morbidity and mortality. Development of methods to propagate adult human intestinal stem cells (ISCs) and pluripotent stem cells raises the possibility of using stem cell-based therapy for patients with monogenic and polygenic forms of intestinal failure. Organoids have demonstrated the capacity to proliferate indefinitely and differentiate into the various cellular lineages of the gut. Genome-editing techniques, including the overexpression of the corrected form of the defective gene, or the use of CRISPR (clustered regularly interspaced short palindromic repeats)/Cas9 to selectively correct the monogenic disease-causing variant within the stem cell, make autologous ISC transplantation a feasible approach. However, numerous techniques still need to be further optimized, including more robust ex vivo ISC expansion, native ISC ablation, and engraftment protocols. Large-animal models can to be used to develop such techniques and protocols and to establish the safety of autologous ISC transplantation because outcomes in such models can be extrapolated more readily to humans.The field of intestinal stem cell biology has exploded over the past 5 years with discoveries related to in vivo and in vitro stem cell identity and function. The goal of this review article is to highlight the potential use of these cells to treat various epithelial disorders of the gut and discuss the various roadblocks that will be encountered in the coming years

Implementation of a roughness sublayer parameterization in the Weather Research and Forecasting model (WRF version 3.7.1) and its evaluation for regional climate simulations

The roughness sublayer (RSL) is one compartment of the surface layer (SL) where turbulence deviates from Monin-Obukhov similarity theory. As the computing power increases, model grid sizes approach the gray zone of turbulence in the energy-containing range and the lowest model layer is located within the RSL. From this perspective, the RSL has an important implication in atmospheric modeling research. However, it has not been explicitly simulated in atmospheric mesoscale models. This study incorporates the RSL model proposed by Harman and Finnigan (2007, 2008) into the Jiménez et al. (2012) SL scheme. A high-resolution simulation performed with the Weather Research and Forecasting model (WRF) illustrates the impacts of the RSL parameterization on the wind, air temperature, and rainfall simulation in the atmospheric boundary layer. As the roughness parameters vary with the atmospheric stability and vegetative phenology in the RSL model, our RSL implementation reproduces the observed surface wind, particularly over tall canopies in the winter season by reducing the root mean square error (RMSE) from 3.1 to 1.8ms-1. Moreover, the improvement is relevant to air temperature (from 2.74 to 2.67amp;thinsp;K of RMSE) and precipitation (from 140 to 135amp;thinsp;mm per month of RMSE). Our findings suggest that the RSL must be properly considered both for better weather and climate simulations and for the application of wind energy and atmospheric dispersion. © 2020 E. Schweizerbart'sche Verlagsbuchhandlung. All rights reserved

Genetic and epigenetic alterations of colorectal cancer

Colorectal cancer (CRC) arise from multi-step carcinogenesis due to genetic mutations and epigenetic modifications of human genome. Genetic mutations and epigenetic modifications were originally established as 2 independent mechanisms contributing to colorectal carcinogenesis. However, recent evidences demonstrate that there are interactions between these 2 mechanisms. Genetic mutations enable disruption of epigenetic controls while epigenetic modifications can initiate genomic instability and carcinogenesis. This review summarized genetic mutations and epigenetic modifications in colorectal carcinogenesis and molecular classification of CRC subtype based on genetic or epigenetic biomarkers for treatment response and prognosis. Molecular subtypes of CRC will permit the implementation of precision medicine with better outcome of management for CRC

The soluble amino-terminal region of HVEM mediates efficient herpes simplex virus type 1 infection of gD receptor-negative cells

<p>Abstract</p> <p>Background</p> <p>Previous studies from our own and other labs reported the surprising finding that the soluble V domain of the herpes simplex virus type 1 (HSV-1) entry receptor nectin-1 can both block HSV infection of receptor-bearing cells and mediate infection of receptor-deficient cells. Here we show that this property is not unique to nectin-1. We generated a pair of truncated, soluble forms of the other major HSV-1 entry receptor, herpes virus entry mediator (HVEM or HveA), and examined its effects on HSV-1 infection of receptor-deficient cells.</p> <p>Results</p> <p>In cultures of CHO-K1 cells, sHveA₁₀₂comprising the two amino-terminal cysteine-rich pseudorepeats (CRPs) of HVEM enabled infection of greater than 80% of the cells at an MOI of 3, while sHveA₁₆₂comprising the complete ectodomain failed to mediate infection. Both sHveA₁₀₂and sHveA₁₆₂blocked infection of CHO-K1 cells stably expressing HVEM in a dose-dependent manner, indicating that both were capable of binding to viral gD. We found that sHveA₁₀₂-mediated infection involves pH-independent endocytosis whereas HSV infection of HVEM-expressing CHO-K1 cells is known to be pH-dependent.</p> <p>Conclusions</p> <p>Our results suggest that the C-terminal portion of the soluble HVEM ectodomain inhibits gD activation and that this effect is neutralized in the full-length form of HVEM in normal infection.</p