Gene regulation by convergent promoters.

Convergent transcription, that is, the collision of sense and antisense transcription, is ubiquitous in mammalian genomes and believed to diminish RNA expression. Recently, antisense transcription downstream of promoters was found to be surprisingly prevalent. However, functional characteristics of affected promoters are poorly investigated.

RAGE/DIAPH1 and atherosclerosis through an evolving lens: Viewing the cell from the "Inside - Out".

Background And Aims: In hyperglycemia, inflammation, oxidative stress and aging, Damage Associated Molecular Patterns (DAMPs) accumulate in conditions such as atherosclerosis. Binding of DAMPs to receptors such as the receptor for advanced glycation end products (RAGE) activates signal transduction cascades that contribute to cellular stress. The cytoplasmic domain (tail) of RAGE (ctRAGE) binds to the formin Diaphanous1 (DIAPH1), which is important for RAGE signaling.

Determinants of p53 DNA binding, gene regulation, and cell fate decisions.

The extent to which transcription factors read and respond to specific information content within short DNA sequences remains an important question that the tumor suppressor p53 is helping us answer. We discuss recent insights into how local information content at p53 binding sites might control modes of p53 target gene activation and cell fate decisions. Significant prior work has yielded data supporting two potential models of how p53 determines cell fate through its target genes: a selective target gene binding and activation model and a p53 level threshold model.

RAGE/DIAPH1 and atherosclerosis through an evolving lens: Viewing the cell from the "Inside - Out".

Background And Aims: In hyperglycemia, inflammation, oxidative stress and aging, Damage Associated Molecular Patterns (DAMPs) accumulate in conditions such as atherosclerosis. Binding of DAMPs to receptors such as the receptor for advanced glycation end products (RAGE) activates signal transduction cascades that contribute to cellular stress. The cytoplasmic domain (tail) of RAGE (ctRAGE) binds to the formin Diaphanous1 (DIAPH1), which is important for RAGE signaling.

Applying the extended parallel process model to understand households' responses to tornado and earthquake risks in Oklahoma.

Oklahoma is a multihazard environment where both natural (e.g., tornadoes) and technological hazards (e.

DIAPH1 mediates progression of atherosclerosis and regulates hepatic lipid metabolism in mice.

Atherosclerosis evolves through dysregulated lipid metabolism interwoven with exaggerated inflammation. Previous work implicating the receptor for advanced glycation end products (RAGE) in atherosclerosis prompted us to explore if Diaphanous 1 (DIAPH1), which binds to the RAGE cytoplasmic domain and is important for RAGE signaling, contributes to these processes. We intercrossed atherosclerosis-prone Ldlr mice with mice devoid of Diaph1 and fed them Western diet for 16 weeks.

The RAGE/DIAPH1 axis: mediator of obesity and proposed biomarker of human cardiometabolic disease.

Overweight and obesity are leading causes of cardiometabolic dysfunction. Despite extensive investigation, the mechanisms mediating the increase in these conditions are yet to be fully understood. Beyond the endogenous formation of advanced glycation endproducts (AGEs) in overweight and obesity, exogenous sources of AGEs accrue through the heating, production, and consumption of highly processed foods.

Tracing app technology: an ethical review in the COVID-19 era and directions for post-COVID-19.

Unlabelled: We conducted a systematic literature review on the ethical considerations of the use of contact tracing app technology, which was extensively implemented during the COVID-19 pandemic. The rapid and extensive use of this technology during the COVID-19 pandemic, while benefiting the public well-being by providing information about people's mobility and movements to control the spread of the virus, raised several ethical concerns for the post-COVID-19 era. To investigate these concerns for the post-pandemic situation and provide direction for future events, we analyzed the current ethical frameworks, research, and case studies about the ethical usage of tracing app technology.

Glycation and a Spark of ALEs (Advanced Lipoxidation End Products) - Igniting RAGE/Diaphanous-1 and Cardiometabolic Disease.

Obesity and non-alcoholic fatty liver disease (NAFLD) are on the rise world-wide; despite fervent advocacy for healthier diets and enhanced physical activity, these disorders persist unabated and, long-term, are major causes of morbidity and mortality. Numerous fundamental biochemical and molecular pathways participate in these events at incipient, mid- and advanced stages during atherogenesis and impaired regression of established atherosclerosis. It is proposed that upon the consumption of high fat/high sugar diets, the production of receptor for advanced glycation end products (RAGE) ligands, advanced glycation end products (AGEs) and advanced lipoxidation end products (ALEs), contribute to the development of foam cells, endothelial injury, vascular inflammation, and, ultimately, atherosclerosis and its consequences.

The RAGE/DIAPH1 Signaling Axis & Implications for the Pathogenesis of Diabetic Complications.

Increasing evidence links the RAGE (receptor for advanced glycation end products)/DIAPH1 (Diaphanous 1) signaling axis to the pathogenesis of diabetic complications. RAGE is a multi-ligand receptor and through these ligand-receptor interactions, extensive maladaptive effects are exerted on cell types and tissues targeted for dysfunction in hyperglycemia observed in both type 1 and type 2 diabetes. Recent evidence indicates that RAGE ligands, acting as damage-associated molecular patterns molecules, or DAMPs, through RAGE may impact interferon signaling pathways, specifically through upregulation of IRF7 (interferon regulatory factor 7), thereby heralding and evoking pro-inflammatory effects on vulnerable tissues.

COVID-19, Scarce Resources and Priority Ethics: Why Should Maximizers Be More Conservative?

Background: The principle of maximization, which roughly means that we should save more lives and more years of life, is usually taken for granted by the health community. This principle is even more forceful in crises like the COVID-19 pandemic, where we have scarce resources which can be allocated only to some patients. However, the standard consequentialist version of this principle can be challenging particularly when we have to reallocate a resource that has already been given to a patient.

p63 and p53: Collaborative Partners or Dueling Rivals?

The tumor suppressor p53 and its oncogenic sibling p63 (ΔNp63) direct opposing fates in tumor development. These paralog proteins are transcription factors that elicit their tumor suppressive and oncogenic capacity through the regulation of both shared and unique target genes. Both proteins predominantly function as activators of transcription, leading to a paradigm shift away from ΔNp63 as a dominant negative to p53 activity.

Inflammation Meets Metabolism: Roles for the Receptor for Advanced Glycation End Products Axis in Cardiovascular Disease.

Fundamental modulation of energy metabolism in immune cells is increasingly being recognized for the ability to impart important changes in cellular properties. In homeostasis, cells of the innate immune system, such as monocytes, macrophages and dendritic cells (DCs), are enabled to respond rapidly to various forms of acute cellular and environmental stress, such as pathogens. In chronic stress milieus, these cells may undergo a re-programming, thereby triggering processes that may instigate tissue damage and failure of resolution.

Diabetes and Cardiovascular Complications: The Epidemics Continue.

Purpose Of Review: The cardiovascular complications of type 1 and 2 diabetes are major causes of morbidity and mortality. Extensive efforts have been made to maximize glycemic control; this strategy reduces certain manifestations of cardiovascular complications. There are drawbacks, however, as intensive glycemic control does not impart perennial protective benefits, and these efforts are not without potential adverse sequelae, such as hypoglycemic events.

Structural Inequalities Established the Architecture for COVID-19 Pandemic Among Native Americans in Arizona: a Geographically Weighted Regression Perspective.

Native Americans are disproportionately affected by COVID-19. The present study explores whether areas with high percentages of Native American residents are experiencing the equal risks of contracting COVID-19 by examining how the relationships between structural inequalities and confirmed COVID-19 cases spatially vary across Arizona using a geographically weighted regression (GWR). GWR helps with the identification of areas with high confirmed COVID-19 cases in Arizona and with understanding of which predictors of social inequalities are associated with confirmed COVID-19 cases at specific locations.

An Exploratory Study on Pseudo-Data Generation in Prescription and Adverse Drug Reaction Extraction.

Prescription information and adverse drug reactions (ADR) are two components of detailed medication instructions that can benefit many aspects of clinical research. Automatic extraction of this information from free-text narratives via Information Extraction (IE) can open it up to downstream uses. IE is commonly tackled by supervised Natural Language Processing (NLP) systems which rely on annotated training data.

Evaluation of global simulations of aerosol particle and cloud condensation nuclei number, with implications for cloud droplet formation.

A total of 16 global chemistry transport models and general circulation models have participated in this study; 14 models have been evaluated with regard to their ability to reproduce the near-surface observed number concentration of aerosol particles and cloud condensation nuclei (CCN), as well as derived cloud droplet number concentration (CDNC). Model results for the period 2011-2015 are compared with aerosol measurements (aerosol particle number, CCN and aerosol particle composition in the submicron fraction) from nine surface stations located in Europe and Japan. The evaluation focuses on the ability of models to simulate the average across time state in diverse environments and on the seasonal and short-term variability in the aerosol properties.

Comparison of genotoxic versus nongenotoxic stabilization of p53 provides insight into parallel stress-responsive transcriptional networks.

The tumor suppressor protein p53 is activated in response to diverse intrinsic and extrinsic cellular stresses and controls a broad cell-protective gene network. Whether p53:DNA binding and subsequent transcriptional activation differs downstream of these diverse intrinsic and extrinsic activators is controversial. Using primary human fibroblasts, we assessed the genome-wide profile of p53 binding, chromatin structure, and transcriptional dynamics after either genotoxic or nongenotoxic activation of p53.

Atomic-Scale Characterization of Graphene p-n Junctions for Electron-Optical Applications.

Graphene p-n junctions offer a potentially powerful approach toward controlling electron trajectories via collimation and focusing in ballistic solid-state devices. The ability of p-n junctions to control electron trajectories depends crucially on the doping profile and roughness of the junction. Here, we use four-probe scanning tunneling microscopy and spectroscopy (STM/STS) to characterize two state-of-the-art graphene p-n junction geometries at the atomic scale, one with CMOS polySi gates and another with naturally cleaved graphite gates.

Social Networks and Health in a Prison Unit.

Although a growing body of research documents lasting health consequences of incarceration, little is known about how confinement affects inmates' health while incarcerated. In this study, we examine the role of peer social integration and prisoners' self-reported health behaviors (smoking, exercise, perception of health, and depression) in a prison unit. We also consider whether inmates with similar health characteristics cluster within the unit.

Correntropy Based Matrix Completion.

This paper studies the matrix completion problems when the entries are contaminated by non-Gaussian noise or outliers. The proposed approach employs a nonconvex loss function induced by the maximum correntropy criterion. With the help of this loss function, we develop a rank constrained, as well as a nuclear norm regularized model, which is resistant to non-Gaussian noise and outliers.

Preferences Regarding Return of Genomic Results to Relatives of Research Participants, Including after Participant Death: Empirical Results from a Cancer Biobank.

Data are lacking with regard to participants' perspectives on return of genetic research results to relatives, including after the participant's death. This paper reports descriptive results from 3,630 survey respondents: 464 participants in a pancreatic cancer biobank, 1,439 family registry participants, and 1,727 healthy individuals. Our findings indicate that most participants would feel obligated to share their results with blood relatives while alive and would want results to be shared with relatives after their death.

Returning a Research Participant's Genomic Results to Relatives: Analysis and Recommendations.

Genomic research results and incidental findings with health implications for a research participant are of potential interest not only to the participant, but also to the participant's family. Yet investigators lack guidance on return of results to relatives, including after the participant's death. In this paper, a national working group offers consensus analysis and recommendations, including an ethical framework to guide investigators in managing this challenging issue, before and after the participant's death.