Control of meiotic entry by dual inhibition of a key mitotic transcription factor.

The mitosis to meiosis transition requires dynamic changes in gene expression, but whether and how the mitotic transcriptional machinery is regulated during this transition is unknown. In budding yeast, SBF and MBF transcription factors initiate the mitotic gene expression program. Here, we report two mechanisms that work together to restrict SBF activity during meiotic entry: repression of the SBF-specific Swi4 subunit through LUTI-based regulation and inhibition of SBF by Whi5, a functional homolog of the Rb tumor suppressor.

Control of meiotic entry by dual inhibition of a key mitotic transcription factor.

The mitosis to meiosis transition requires dynamic changes in gene expression, but whether and how the mitotic transcriptional machinery is regulated during this transition is unknown. In budding yeast, SBF and MBF transcription factors initiate the mitotic gene expression program. Here, we report two mechanisms that work together to restrict SBF activity during meiotic entry: repression of the SBF-specific Swi4 subunit through LUTI-based regulation and inhibition of SBF by Whi5, a homolog of the Rb tumor suppressor.

High Coronary Artery Calcium Score Is Associated With Increased Major Adverse Cardiac Events After Liver Transplantation.

Unlabelled: Liver transplantation (LT) candidates frequently have multiple cardiovascular risk factors, and cardiovascular disease is a major cause of morbidity and mortality after LT. Coronary artery calcium (CAC) scores are a noninvasive assessment of coronary artery disease using computed tomography. This study examines CAC scores and cardiac risk factors and their association with outcomes after LT.

Pseudouridine synthases modify human pre-mRNA co-transcriptionally and affect pre-mRNA processing.

Pseudouridine is a modified nucleotide that is prevalent in human mRNAs and is dynamically regulated. Here, we investigate when in their life cycle mRNAs become pseudouridylated to illuminate the potential regulatory functions of endogenous mRNA pseudouridylation. Using single-nucleotide resolution pseudouridine profiling on chromatin-associated RNA from human cells, we identified pseudouridines in nascent pre-mRNA at locations associated with alternatively spliced regions, enriched near splice sites, and overlapping hundreds of binding sites for RNA-binding proteins.

Two Acute Liver Injuries in a Patient With Malnutrition.

Chronic starvation and refeeding have been associated with liver injury (LI). We present a patient with anorexia nervosa who exhibited both phenomena of malnutrition-related LI. At presentation, aspartate aminotransferase (AST) and alanine aminotransferase (ALT) were elevated at 154 and 136 U/L, respectively, and rose rapidly to peaks of 750 and 638 U/L, respectively, as nutrition was introduced.

A large-scale binding and functional map of human RNA-binding proteins.

Many proteins regulate the expression of genes by binding to specific regions encoded in the genome. Here we introduce a new data set of RNA elements in the human genome that are recognized by RNA-binding proteins (RBPs), generated as part of the Encyclopedia of DNA Elements (ENCODE) project phase III. This class of regulatory elements functions only when transcribed into RNA, as they serve as the binding sites for RBPs that control post-transcriptional processes such as splicing, cleavage and polyadenylation, and the editing, localization, stability and translation of mRNAs.

Timing is everything: Early do-not-resuscitate orders in the intensive care unit and patient outcomes.

Background: The use of Do-Not-Resuscitate (DNR) orders has increased but many are placed late in the dying process. This study is to determine the association between the timing of DNR order placement in the intensive care unit (ICU) and nurses' perceptions of patients' distress and quality of death.

Methods: 200 ICU patients and the nurses (n = 83) who took care of them during their last week of life were enrolled from the medical ICU and cardiac care unit of New York Presbyterian Hospital/Weill Cornell Medicine in Manhattan and the surgical ICU at the Brigham and Women's Hospital in Boston.

Comparing Changes in Controlled Substance Prescribing Trends by Provider Type.

Background And Objectives: Forty-nine out of 50 states have implemented Prescription Drug Monitoring Programs (PDMPs) to monitor controlled substance (CS) prescribing. PDMPs change health care provider behavior, but few studies have examined changes in CS prescription by health care provider type.

Methods: Aggregated yearly data, including number of CS prescriptions, doses, and doses per prescription by health care provider type (physician, advanced practice registered nurse [APRN], and dentist) for each year from 2011 to 2017 was provided by the state PDMP, Kentucky All Schedule Prescription Electronic Reporting System (KASPER).

mRNA structure determines modification by pseudouridine synthase 1.

Pseudouridine (Ψ) is a post-transcriptional RNA modification that alters RNA-RNA and RNA-protein interactions that affect gene expression. Messenger RNA pseudouridylation was recently discovered as a widespread and conserved phenomenon, but the mechanisms responsible for selective, regulated pseudouridylation of specific sequences within mRNAs were unknown. Here, we have revealed mRNA targets for five pseudouridine synthases and probed the determinants of mRNA target recognition by the predominant mRNA pseudouridylating enzyme, Pus1, by developing high-throughput kinetic analysis of pseudouridylation in vitro.

Clinical and Socioeconomic Predictors of Heart Failure Readmissions: A Review of Contemporary Literature.

Heart failure represents a clinical syndrome that results from a constellation of disease processes affecting myocardial function. Although recent studies have suggested a declining or stable incidence of heart failure, patients with heart failure continue to have high hospitalization and readmission rates, resulting in a substantial economic and public health burden. We searched PubMed and Google Scholar to identify published literature from 1998 through 2018 using the following keywords: heart failure, readmissions, predictors, prediction models, and interventions.

A cross-sectional survey of coronary plaque composition in individuals on non-statin lipid lowering drug therapies and undergoing coronary computed tomography angiography.

Introduction: Non-statin therapy (NST) is used as second-line treatment when statin monotherapy is inadequate or poorly tolerated.

Objective: To determine the association of NST with plaque composition, alone or in combination with statins, in patients undergoing coronary computed tomography angiography (coronary CTA).

Methods: From the multicenter CONFIRM registry, we analyzed individuals who underwent coronary CTA with known lipid-lowering therapy status and without prior coronary artery disease at baseline.

Sequence, Structure, and Context Preferences of Human RNA Binding Proteins.

RNA binding proteins (RBPs) orchestrate the production, processing, and function of mRNAs. Here, we present the affinity landscapes of 78 human RBPs using an unbiased assay that determines the sequence, structure, and context preferences of these proteins in vitro by deep sequencing of bound RNAs. These data enable construction of "RNA maps" of RBP activity without requiring crosslinking-based assays.

Beyond Pain: Nurses' Assessment of Patient Suffering, Dignity, and Dying in the Intensive Care Unit.

Context: Deaths in the intensive care unit (ICU) are increasingly common in the U.S., yet little is known about patients' experiences at the end of life in the ICU.

Accuracy of name and age data provided about network members in a social network study of people who use drugs: implications for constructing sociometric networks.

Purpose: Network analysis has become increasingly popular in epidemiologic research, but the accuracy of data key to constructing risk networks is largely unknown. Using network data from people who use drugs (PWUDs), the study examined how accurately PWUD reported their network members' (i.e.

Developmental Dynamics of X-Chromosome Dosage Compensation by the DCC and H4K20me1 in C. elegans.

In Caenorhabditis elegans, the dosage compensation complex (DCC) specifically binds to and represses transcription from both X chromosomes in hermaphrodites. The DCC is composed of an X-specific condensin complex that interacts with several proteins. During embryogenesis, DCC starts localizing to the X chromosomes around the 40-cell stage, and is followed by X-enrichment of H4K20me1 between 100-cell to comma stage.

The lifetime medical cost savings from preventing HIV in the United States.

Objective: Enhanced HIV prevention interventions, such as preexposure prophylaxis for high-risk individuals, require substantial investments. We sought to estimate the medical cost saved by averting 1 HIV infection in the United States.

Methods: We estimated lifetime medical costs in persons with and without HIV to determine the cost saved by preventing 1 HIV infection.

The clinical and economic impact of point-of-care CD4 testing in mozambique and other resource-limited settings: a cost-effectiveness analysis.

Background: Point-of-care CD4 tests at HIV diagnosis could improve linkage to care in resource-limited settings. Our objective is to evaluate the clinical and economic impact of point-of-care CD4 tests compared to laboratory-based tests in Mozambique.

Methods And Findings: We use a validated model of HIV testing, linkage, and treatment (CEPAC-International) to examine two strategies of immunological staging in Mozambique: (1) laboratory-based CD4 testing (LAB-CD4) and (2) point-of-care CD4 testing (POC-CD4).

HIV, tuberculosis, and noncommunicable diseases: what is known about the costs, effects, and cost-effectiveness of integrated care?

Unprecedented investments in health systems in low- and middle-income countries (LMICs) have resulted in more than 8 million individuals on antiretroviral therapy. Such individuals experience dramatically increased survival but are increasingly at risk of developing common noncommunicable diseases (NCDs). Integrating clinical care for HIV, other infectious diseases, and NCDs could make health services more effective and provide greater value.