Inflammation causes insulin resistance in mice via interferon regulatory factor 3 (IRF3)-mediated reduction in FAHFA levels.

Obesity-induced inflammation causes metabolic dysfunction, but the mechanisms remain elusive. Here we show that the innate immune transcription factor interferon regulatory factor (IRF3) adversely affects glucose homeostasis through induction of the endogenous FAHFA hydrolase androgen induced gene 1 (AIG1) in adipocytes. Adipocyte-specific knockout of IRF3 protects male mice against high-fat diet-induced insulin resistance, whereas overexpression of IRF3 or AIG1 in adipocytes promotes insulin resistance on a high-fat diet.

Climate change is poised to alter mountain stream ecosystem processes via organismal phenological shifts.

Climate change is affecting the phenology of organisms and ecosystem processes across a wide range of environments. However, the links between organismal and ecosystem process change in complex communities remain uncertain. In snow-dominated watersheds, snowmelt in the spring and early summer, followed by a long low-flow period, characterizes the natural flow regime of streams and rivers.

Streptavidin-Affinity Grid Fabrication for Cryo-Electron Microscopy Sample Preparation.

Streptavidin affinity grids provide strategies to overcome many commonly encountered cryo-electron microscopy (cryo-EM) sample preparation challenges, including sample denaturation and preferential orientations that can occur due to the air-water interface. Streptavidin affinity grids, however, are currently utilized by few cryo-EM labs because they are not commercially available and require a careful fabrication process. Two-dimensional streptavidin crystals are grown onto a biotinylated lipid monolayer that is applied directly to standard holey-carbon cryo-EM grids.

Tricuspid surgery at time of mitral surgery improves survival free from severe tricuspid regurgitation but not quality of life.

Objective: The choice to operate on moderate tricuspid regurgitation (TR) during mitral surgery is challenging owing to limited mid-term data. We assess whether concomitant tricuspid operations improve mid-term quality of life, morbidity, or mortality.

Methods: An institutional database identified mitral surgery recipients with moderate TR at the time of surgery from 2010 to 2019.

Center Volume Predicts Improved Early Outcomes in Multiorgan Heart Transplantation.

Purpose: Center volume is associated with improved survival after isolated heart transplant, but its impact on multiorgan heart transplant (MHT) outcomes is unknown. This study examines the impact of institutional MHT volume on MHT outcomes.

Methods: Adult patients undergoing first time MHT from 2011 to 2021 were identified in the United Network for Organ Sharing database.

Emerging Racial Differences in Heart Transplant Waitlist Outcomes for Patients on Temporary Mechanical Circulatory Support.

Temporary mechanical circulatory support (tMCS) is increasingly used for patients awaiting heart transplantation. Although examples of systemic inequity in cardiac care have been described, biases in tMCS use are not well characterized. This study explores the racial disparities in tMCS use and waitlist outcomes.

180 years of marine animal diversity as perceived by public media in southern Brazil.

Commoditization of marine resources has dramatically increased anthropogenic footprints on coastal and ocean systems, but the scale of these impacts remain unclear due to a pervasive lack of historical baselines. Through the analysis of historical newspapers, this paper explores changes in marine animals (vertebrates and invertebrates) targeted by historical fisheries in southern Brazil since the late 19th century. The investigation of historical newspaper archives revealed unprecedented information on catch composition, and perceived social and economic importance of key species over decades, predating official national-level landing records.

Prosthesis Choice in Dialysis Patients Undergoing Mitral Valve Replacement.

Background: Patients with renal disease on dialysis have significant comorbidity limiting life expectancy; however, these patients may experience accelerated prosthetic valve degeneration. The purpose of this study was to examine the impact of prosthesis choice on outcomes in dialysis patients undergoing mitral valve replacement (MVR) at our high-volume academic center.

Methods: Adults undergoing MVR were retrospectively reviewed between January 2002 and November 2019.

Bridging archaeology and marine conservation in the Neotropics.

Anthropogenic impacts on tropical and subtropical coastal environments are increasing at an alarming rate, compromising ecosystem functions, structures and services. Understanding the scale of marine population decline and diversity loss requires a long-term perspective that incorporates information from a range of sources. The Southern Atlantic Ocean represents a major gap in our understanding of pre-industrial marine species composition.

Extended criteria donor organ use for heart-lung transplantation in the modern era.

Background: Demand for donor hearts and lungs exceeds their supply. Extended Criteria Donor (ECD) organs are used to help meet this demand, but their impact on heart-lung transplantation outcomes is poorly characterized.

Methods And Results: The United Network for Organ Sharing was queried for data on adult heart-lung transplantation recipients (n = 447) from 2005‒2021.

Heart-kidney transplant versus heart transplant in the obese: a propensity-matched analysis.

Objectives: The decision to perform simultaneous heart-kidney transplant (HKT) rather than isolated heart transplant (IHT) for patients with advanced kidney disease is challenging. Limited data exist to guide this decision in obese patients. We sought to compare mortality after HKT and IHT in obese patients with non-dialysis-dependent kidney disease.

Antithrombotic therapy for durable left ventricular assist devices - current strategies and future directions.

Left ventricular assist devices (LVADs) improve survival and quality of life for patients with advanced heart failure but are associated with high rates of thromboembolic and hemorrhagic complications. Antithrombotic therapy is required following LVAD implantation, though practices vary. Identifying a therapeutic strategy that minimizes the risks of thromboembolic and hemorrhagic complications is critical to optimizing patient outcomes and is an area of active investigation.

The structure of a polyketide synthase bimodule core.

Polyketide synthases (PKSs) are predominantly microbial biosynthetic enzymes. They assemble highly potent bioactive natural products from simple carboxylic acid precursors. The most versatile families of PKSs are organized as assembly lines of functional modules.

Waitlist Trends in Heart-Liver Transplantation With Updated US Heart Allocation System.

Background: In October 2018, the United States implemented a change in the donor heart allocation policy from a three-tiered to a six-tiered status system. The purpose of the current study was to examine changes in waitlist patterns among patients listed for concomitant heart-liver transplantation with implementation of the new allocation system.

Methods: Patients listed for heart-liver transplantation between January 1, 2012, and June 30, 2021, were identified from the United Network for Organ Sharing database.

Interaction between donor obesity and prolonged donor ischemic time in heart transplantation.

Background: The purpose of the study was to determine the impact of donor obesity on outcomes following heart transplantation in the setting of routine (<4 h) and prolonged (≥4 h) organ ischemic times.

Methods: Retrospective review of the 2000-2020 United Network for Organ Sharing Database was performed to identify adult heart transplant recipients and donors. Nearest-neighbor propensity score matching by donor obesity was performed separately among routine and prolonged cohorts, with Kaplan-Meier survival estimates used to assess survival at 5 years following transplantation.

In situ identification of cellular drug targets in mammalian tissue.

The lack of tools to observe drug-target interactions at cellular resolution in intact tissue has been a major barrier to understanding in vivo drug actions. Here, we develop clearing-assisted tissue click chemistry (CATCH) to optically image covalent drug targets in intact mammalian tissues. CATCH permits specific and robust in situ fluorescence imaging of target-bound drug molecules at subcellular resolution and enables the identification of target cell types.

Failure to rescue: obesity increases the risk of mortality following early graft failure in heart transplantation in UNOS database patients.

Objectives: Early graft failure (EGF) is a devastating postoperative complication following heart transplant. Institutional studies have modelled donor and recipient risk factors predictive of graft failure. To date, no studies have assessed specific recipient profiles associated with mortality after recipients suffer from EGF.

Structure of the human SAGA coactivator complex.

The SAGA complex is a regulatory hub involved in gene regulation, chromatin modification, DNA damage repair and signaling. While structures of yeast SAGA (ySAGA) have been reported, there are noteworthy functional and compositional differences for this complex in metazoans. Here we present the cryogenic-electron microscopy (cryo-EM) structure of human SAGA (hSAGA) and show how the arrangement of distinct structural elements results in a globally divergent organization from that of yeast, with a different interface tethering the core module to the TRRAP subunit, resulting in a dramatically altered geometry of functional elements and with the integration of a metazoan-specific splicing module.

Phospholipase Cγ2 regulates endocannabinoid and eicosanoid networks in innate immune cells.

Human genetic studies have pointed to a prominent role for innate immunity and lipid pathways in immunological and neurodegenerative disorders. Our understanding of the composition and function of immunomodulatory lipid networks in innate immune cells, however, remains incomplete. Here, we show that phospholipase Cγ2 (PLCγ2 or PLCG2)-mutations in which are associated with autoinflammatory disorders and Alzheimer's disease-serves as a principal source of diacylglycerol (DAG) pools that are converted into a cascade of bioactive endocannabinoid and eicosanoid lipids by DAG lipase (DAGL) and monoacylglycerol lipase (MGLL) enzymes in innate immune cells.

HCV-Positive Allograft Use in Heart Transplantation Is Associated With Increased Access to Overdose Donors and Reduced Waitlist Mortality Without Compromising Outcomes.

Background: Because of ongoing shortages of donors for heart transplantation, the use of donor candidates whose availabilities are the result of drug overdoses (ODs) has become increasingly prevalent, even though these donors carry a high preponderance of the now curable hepatitis C virus (HCV). This study investigated temporal trends and regional variabilities in HVC-positive (HCV+) allograft use in heart transplantation and assessed the relationship between the use of HCV+ graft donors and the use of OD donors as well as assessing waitlist and post-transplant outcomes.

Methods And Results: A retrospective review of the United Network for Organ Sharing database assessed adults listed for heart transplantation.

Assessing predicted heart mass size matching in obese heart transplant recipients.

Background: Predicted heart mass (PHM) is currently the most reliable metric for donor-recipient size matching in heart transplantation. Undersizing PHM donor-recipient match more than 20% independently predicts reduced survival. However, it is unclear if this is the case in obese recipients, in whom size matching can be challenging.