Cardiac-targeted delivery of a novel Drp1 inhibitor for acute cardioprotection.

Dynamin-related protein 1 (Drp1) is a mitochondrial fission protein and a viable target for cardioprotection against myocardial ischaemia-reperfusion injury. Here, we reported a novel Drp1 inhibitor (DRP1i1), delivered using a cardiac-targeted nanoparticle drug delivery system, as a more effective approach for achieving acute cardioprotection. DRP1i1 was encapsulated in cubosome nanoparticles with conjugated cardiac-homing peptides (NanoDRP1i1) and the encapsulation efficiency was 99.

Coronary atherosclerosis in athletes: emerging concepts and preventive strategies.

There should be no assumption that an athlete is immune to coronary artery disease (CAD), even when traditional cardiovascular (CV) risk factors appear well-managed. Excelling in certain aspects of health does not equate to total CV protection. Recent data from cardiac imaging studies have raised the possibility that long-term, high-volume, high-intensity endurance exercise is associated with coronary atherosclerosis.

Small Heart Size and Premature Death in 366,484 Individuals With Normal Ejection Fraction.

Background: In patients with preserved left ventricular ejection fraction (LVEF), small ventricular size has been associated with reduced functional capacity, but its impact on clinical outcomes is unclear.

Objectives: The goal of this study was to determine the relationship between small heart size and premature mortality within a large multicenter adult patient cohort with transthoracic echocardiographic examinations.

Methods: We divided 366,484 individuals with LVEF ≥50% (including a subset of 279,442 individuals with high-normal LVEF ≥60%) by sex and increasing quartiles for LV end-diastolic volume (LVEDV), LVEDV indexed to body surface area (LVEDVi), and LV end-diastolic diameter to assess associations with 5-year mortality through linkage with the National Death Index.

The β Common Cytokine Receptor Family Reveals New Functional Paradigms From Structural Complexities.

Cytokines are small proteins that are critical for controlling the growth and activity of hematopoietic cells by binding to cell surface receptors and transmitting signals across membranes. The β common (βc) cytokine receptor family, consisting of the granulocyte-macrophage colony-stimulating factor (GM-CSF), interleukin (IL)-3, and IL-5 cytokine receptors, is an architype of the heterodimeric cytokine receptor systems. We now know that signaling by cytokine receptors is not always an "all or none" phenomenon.

Going beyond cell clustering and feature aggregation: Is there single cell level information in single-cell ATAC-seq data?

Single-cell Assay for Transposase Accessible Chromatin with sequencing (scATAC-seq) has become a widely used method for investigating chromatin accessibility at single-cell resolution. However, the resulting data is highly sparse with most data entries being zeros. As such, currently available computational methods for scATAC-seq feature a range of transformation procedures to extract meaningful information from the sparse data.

Genetics, Fitness and Left Ventricular Remodeling: The Current State of Play.

Cardiorespiratory fitness (CRF) exists on a spectrum and is driven by a constellation of factors including genetic and environmental differences. This results in wide inter-individual variation in baseline CRF and the ability to improve CRF with regular endurance exercise training. As opposed to monogenic conditions, CRF is described as a complex genetic trait as it is believed to be influenced by multiple common genetic variants in addition to exogenous factors.

Your heart can't see what sneakers you are wearing: Exercise training load in endurance athletes is inadequately quantified in sports cardiology - A systematic review.

Background: Training load may be an important factor underlying the (patho-)physiologic cardiovascular adaptations from endurance exercise. Yet quantifying training load remains challenging due to the complexity of its components (Frequency, Intensity, Time, and Type; F.I.

Dynamic tracking of native precursors in adult mice.

Hematopoietic dysfunction has been associated with a reduction in the number of active precursors. However, precursor quantification at homeostasis and under diseased conditions is constrained by the scarcity of available methods. To address this issue, we optimized a method for quantifying a wide range of hematopoietic precursors.

Using multiplexed functional data to reduce variant classification inequities in underrepresented populations.

Background: Multiplexed Assays of Variant Effects (MAVEs) can test all possible single variants in a gene of interest. The resulting saturation-style functional data may help resolve variant classification disparities between populations, especially for Variants of Uncertain Significance (VUS).

Methods: We analyzed clinical significance classifications in 213,663 individuals of European-like genetic ancestry versus 206,975 individuals of non-European-like genetic ancestry from All of Us and the Genome Aggregation Database.

Collagen and Vascular Changes in the Scapholunate Ligament Following Injury: An Immunohistochemical Study.

Purpose: The scapholunate ligament (SLL) is the most frequently injured wrist ligament. The aim of this study was to investigate cellular and extracellular changes within the SLL following injury.

Methods: Fifteen SLLs were harvested, ranging between 39 days to 20 years from time of injury.

KIF18A inhibition: the next big player in the search for cancer therapeutics.

Kinesin-like protein 18A (KIF18A) is a member of the kinesin family of molecular motor proteins, which utilise energy from the hydrolysis of adenosine triphosphate (ATP) to regulate critical cellular processes such as chromosome movement and microtubule dynamics. KIF18A plays a vital role in controlling microtubule length, which is crucial for maintaining proper cell function and division. Notably, increased expression levels of KIF18A have been observed in various types of cancer, indicating its potential involvement in tumour progression.

GGNBP2 regulates MDA5 sensing triggered by self double-stranded RNA following loss of ADAR1 editing.

Adenosine-to-inosine (A-to-I) editing of double-stranded RNA (dsRNA) by ADAR1 is an essential modifier of the immunogenicity of cellular dsRNA. The role of MDA5 in sensing unedited cellular dsRNA and the downstream activation of type I interferon (IFN) signaling are well established. However, we have an incomplete understanding of pathways that modify the response to unedited dsRNA.

Epilepsy and Cardiac Arrhythmias: A State-of-the-Art Review.

Epilepsy is an important cause of disability and mortality worldwide. It can be frequently misdiagnosed, and detailed history and relevant investigations are needed to differentiate epilepsy from syncope. Electroencephalogram is a key noninvasive assessment of neurological function, and the diagnostic yield is increased when performed for an extended period in the ambulatory setting with concurrent electrocardiogram and video monitoring.

Australian healthcare workers' views on artificial intelligence in BreastScreen: Results of a mixed method survey study.

Introduction: The evolving role of Artificial Intelligence (AI) in medicine, particularly in radiology and population-based breast cancer screening programs, offers potential accuracy gains and efficiency improvements. However, successful implementation requires understanding of healthcare workers' views on AI, which this study aims to explore within the Australian BreastScreen program.

Methods: An online survey was distributed to clinical staff involved in breast imaging, collecting responses from November 2022 to April 2023.

Proinsulin C-peptide is a major source of HLA-DQ8 restricted hybrid insulin peptides recognized by human islet-infiltrating CD4 T cells.

Type 1 diabetes (T1D) is an autoimmune disease that develops when T cells destroy the insulin-producing beta cells that reside in the pancreatic islets. Immune cells, including T cells, infiltrate the islets and gradually destroy the beta cells. Human islet-infiltrating CD4 T cells recognize peptide epitopes derived from proinsulin, particularly C-peptide.

The role of STK11/LKB1 in cancer biology: implications for ovarian tumorigenesis and progression.

STK11 (serine-threonine kinase 11), also known as LKB1 (liver kinase B1) is a highly conserved master kinase that regulates cellular metabolism and polarity through a complex signaling network involving AMPK and 12 other AMPK-related kinases. Germline mutations in have been causatively linked to Peutz-Jeghers Syndrome (PJS), an autosomal dominant hereditary disease with high cancer susceptibility. The identification of inactivating somatic mutations in in different types of cancer further supports its tumor suppressive role.

A minority of proliferating human CD4 T cells in antigen-driven proliferation assays are antigen specific.

Antigen-driven T-cell proliferation is often measured using fluorescent dye dilution assays, such as the CFSE-based proliferation assay. Dye dilution assays have been powerful tools to detect human CD4 T-cell responses, particularly against autoantigens. However, it is not known how many cells within the proliferating population are specific for the stimulating antigen.

Structure, function, surf, repeat: A week at Lorne Proteins 2024.

Since 1976, the Lorne Proteins Conference has been a key gathering for protein scientists, combining cutting-edge research with community engagement in a picturesque corner of the world. Renowned for its diverse international speakers and collaborative spirit, the conference looks forward to its 50 anniversary in 2025.

Combined inhibition of histone methyltransferases EZH2 and DOT1L is an effective therapy for neuroblastoma.

Background: The child cancer, neuroblastoma (NB), is characterised by a low incidence of mutations and strong oncogenic embryonal driver signals. Many new targeted epigenetic modifier drugs have failed in human trials as monotherapy.

Methods: We performed a high-throughput, combination chromatin-modifier drug screen against NB cells.

Left ventricular size and heart failure: A cardiac MRI assessment of 38,129 individuals from the UK Biobank.

Background: Previous studies suggest that prevalent heart failure (HF) differs based on left ventricular ejection fraction (LVEF) and left ventricular (LV) chamber size. Furthermore, the prevalence of HF with preserved ejection fraction (HFpEF) is often considered approaching, or exceeding that of HF with reduced ejection fraction in the community.

Aim: The aim of this study was to evaluate prevalent and incident HF based on LVEF and CMR-determined LV size within a large community-dwelling cohort.

Left Ventricular Volume as a Predictor of Exercise Capacity and Functional Independence in Individuals with Normal Ejection Fraction.

Aims: Low cardiorespiratory fitness (CRF) is associated with functional disability, heart failure and mortality. Left ventricular (LV) end-diastolic volume (LVEDV) has been linked with CRF, but its utility as a diagnostic marker of low CRF has not been tested.

Methods: This multi-center international cohort examined the relationship between LV size on echocardiography and CRF (peak oxygen uptake [peak VO2] from cardiopulmonary exercise testing) in individuals with LV ejection fraction ≥50%.