Involvement of GPx-3 in the Reciprocal Control of Redox Metabolism in the Leukemic Niche

The bone marrow (BM) microenvironment plays a crucial role in the development and progression of leukemia (AML). Intracellular reactive oxygen species (ROS) are involved in the regulation of the biology of leukemia-initiating cells, where the antioxidant enzyme GPx-3 could be involved as a determinant of cellular self-renewal. Little is known however about the role of the microenvironment in the control of the oxidative metabolism of AML cells. In the present study, a coculture model of BM mesenchymal stromal cells (MSCs) and AML cells (KG1a cell-line and primary BM blasts) was used to explore this metabolic pathway. MSC-contact, rather than culture with MSC-conditioned medium, decreases ROS levels and inhibits the Nrf-2 pathway through overexpression of GPx3 in AML cells. The decrease of ROS levels also inactivates p38MAPK and reduces the proliferation of AML cells. Conversely, contact with AML cells modifies MSCs in that they display an increased oxidative stress and Nrf-2 activation, together with a concomitant lowered expression of GPx-3. Altogether, these experiments suggest that a reciprocal control of oxidative metabolism is initiated by direct cell–cell contact between MSCs and AML cells. GPx-3 expression appears to play a crucial role in this cross-talk and could be involved in the regulation of leukemogenesis.     

Using grounded theory as a method for rigorously reviewing literature

This paper offers guidance to conducting a rigorous literature review. We present this in the form of a five-stage process in which we use Grounded Theory as a method. We first probe the guidelines explicated by Webster and Watson, and then we show the added value of Grounded Theory for rigorously analyzing a carefully chosen set of studies; it assures solidly legitimized, in-depth analyses of empirical facts and related insights. This includes, the emergence of new themes, issues and opportunities; interrelationships and dependencies in or beyond a particular area; as well as inconsistencies. If carried out meticulously, reviewing a well-carved out piece of literature by following this guide is likely to lead to more integrated and fruitful theory emergence, something that would enrich many fields in the social sciences.     

Predicting Potential SARS-COV-2 Drugs—In Depth Drug Database Screening Using Deep Neural Network Framework SSnet,Classical Virtual Screening and Docking

Severe Acute Respiratory Syndrome Corona Virus 2 has altered life on a global scale. A concerted effort from research labs around the world resulted in the identification of potential pharmaceutical treatments for CoVID-19 using existing drugs, as well as the discovery of multiple vaccines. During an urgent crisis, rapidly identifying potential new treatments requires global and cross-discipline cooperation, together with an enhanced open-access research model to distribute new ideas and leads. Herein, we introduce an application of a deep neural network based drug screening method, validating it using a docking algorithm on approved drugs for drug repurposing efforts, and extending the screen to a large library of 750,000 compounds for de novo drug discovery effort. The results of large library screens are incorporated into an open-access web interface to allow researchers from diverse fields to target molecules of interest. Our combined approach allows for both the identification of existing drugs that may be able to be repurposed and de novo design of ACE2-regulatory compounds. Through these efforts we demonstrate the utility of a new machine learning algorithm for drug discovery, SSnet, that can function as a tool to triage large molecular libraries to identify classes of molecules with possible efficacy.     

Stability of granular tunnel

We demonstrated that the stability of tunnels made of granular matter is strongly dependent on the grain size, tunnel diameter, and water content inside the granules. Larger tunnel radius, larger grain size, and too much water content tend to destabilize the tunnel. We also developed a model to describe such findings. We identified a phase diagram of stability which is significantly controlled by the granular bond order. For granular bond order of above unity, we always able to build a stable tunnel. For granular bond order of less than unity, we obtained a general expression for estimating the maximum thickness of the stable tunnel. The phenomena related to granular tunnel stability have occurred in human activities (such as a collapse of the sand hole made on the beach) as well as in living animals (such as burrows dug by crabs, antlions, mongoose, beetles, turtles, or some species of rats). To the best of our knowledge, this work is the first exploration regarding the stability of the granular tunnel.     

Leisure of opiate addicts at posttreatment follow-up.

Follow-up data for 1,174 opiate addicts were used to examine leisure reported prior to an interview conducted approximately 6 yrs after admission to treatment for drug abuse. Comparisons of self-reported leisure for the pre- and posttreatment follow-up periods showed an overall shift toward more positive, socially accepted leisure activities at follow-up; more free time was spent with family and with friends who did not use drugs. In addition, positive leisure at follow-up, as well as more positive changes in leisure over time, were related to favorable outcomes on drug use, criminality, and productive activities measures during the year before the follow-up interview. (9 ref) (PsycINFO Database Record (c) 2010 APA, all rights reserved)