Endocannabinoids facilitate transitory reward engagement through retrograde gain-control.

Neuromodulatory signaling is poised to serve as a neural mechanism for gain control, acting as a crucial tuning factor to influence neuronal activity by dynamically shaping excitatory and inhibitory fast neurotransmission. The endocannabinoid (eCB) signaling system, the most widely expressed neuromodulatory system in the mammalian brain, is known to filter excitatory and inhibitory inputs through retrograde, pre-synaptic action. However, whether eCBs exert retrograde gain control to ultimately facilitate reward-seeking behaviors in freely moving mammals is not established.

Modeling predicts facile release of nitrite but not nitric oxide from the thionitrate CHSNO with relevance to nitroglycerin bioactivation.

Nitroglycerin is a potent vasodilator in clinical use since the late 1800s. It functions as a prodrug that is bioactivated by formation of an enzyme-based thionitrate, E-Cys-NO. This intermediate reportedly decomposes to release NO and NO but their relative yields remain controversial.

Multicenter Clinical Performance Evaluation of the NeuMoDx™ CT/NG Assay 2.0.

Background: Given the continued increases in rates of both Chlamydia trachomatis (CT) and Neisseria gonorrhoeae (NG) infection, additional diagnostic assays may be useful in increasing access to testing for these sexually transmitted infections. We evaluated the performance of the NeuMoDx™ CT/NG Assay 2.0 on the NeuMoDx-96 and NeuMoDx-288 Molecular Systems.

GABA and glycine synaptic release on axotomized motoneuron cell bodies promotes motor axon regeneration.

Motor axon regeneration after traumatic nerve injuries is a slow process that adversely influences patient outcomes because muscle reinnervation delays result in irreversible muscle atrophy and suboptimal axon regeneration. This advocates for investigating methods to accelerate motor axon growth. Electrical nerve stimulation and exercise both enhance motor axon regeneration in rodents and patients, but these interventions cannot always be easily implemented.

Clinical, genomic, and proteomic perspectives in the analysis of comorbid conditions in type 2 diabetes mellitus: a retrospective study.

Aim: Type-2 Diabetes Mellitus (T2DM) affects millions globally, with escalating rates. It often leads to undiagnosed complications and commonly coexists with other health conditions. This study investigates two types of prevalent comorbidities related to T2DM-the circulatory system (DCM1) and digestive system diseases (DCM2)-using clinical, genomic and proteomic datasets.

K-mer analysis of long-read alignment pileups for structural variant genotyping.

Accurately genotyping structural variant (SV) alleles is crucial to genomics research. We present a novel method (kanpig) for genotyping SVs that leverages variant graphs and k-mer vectors to rapidly generate accurate SV genotypes. We benchmark kanpig against the latest SV benchmarks and show single-sample genotyping concordance of 82.

Comprehensive genome analysis and variant detection at scale using DRAGEN.

Research and medical genomics require comprehensive, scalable methods for the discovery of novel disease targets, evolutionary drivers and genetic markers with clinical significance. This necessitates a framework to identify all types of variants independent of their size or location. Here we present DRAGEN, which uses multigenome mapping with pangenome references, hardware acceleration and machine learning-based variant detection to provide insights into individual genomes, with ~30 min of computation time from raw reads to variant detection.

People in relationally mobile cultures report higher well-being.

In cultures with high relational mobility, relationships are free and flexible. People can make new friends easily, and they have the freedom to leave unsatisfying relationships. In cultures with low relational mobility, relationships are more fixed, and people have less freedom to leave relationships.

Mitochondrial-derived compartments are multilamellar domains that encase membrane cargo and cytosol.

Preserving the health of the mitochondrial network is critical to cell viability and longevity. To do so, mitochondria employ several membrane remodeling mechanisms, including the formation of mitochondrial-derived vesicles (MDVs) and compartments (MDCs) to selectively remove portions of the organelle. In contrast to well-characterized MDVs, the distinguishing features of MDC formation and composition remain unclear.

The impact of global falsified medicines regulation on healthcare stakeholders in the legitimate pharmaceutical supply chain: a systematic review.

Background: Falsified medicines and their international regulation impacts all healthcare sectors and their actors. These regulations aim to strengthen and protect the global pharmaceutical supply chain against falsified medicines. However, an evaluation of the impacts of these regulations on key stakeholders within the legitimate supply chain have not been explored.

Computational approaches for clinical, genomic and proteomic markers of response to glucagon-like peptide-1 therapy in type-2 diabetes mellitus: An exploratory analysis with machine learning algorithms.

Introduction: In 2021, the International Diabetes Federation reported that 537 million people worldwide are living with diabetes. While glucagon-like peptide-1 agonists provide significant benefits in diabetes management, approximately 40% of patients do not respond well to this therapy. This study aims to enhance treatment outcomes by using machine learning to predict individual response status to glucagon-like peptide-1 therapy.

Disruption of Core Stress Granule Protein Aggregates Promotes CNS Axon Regeneration.

Depletion or inhibition of core stress granule proteins, G3BP1 in mammals and TIAR-2 in , increases axon regeneration in injured neurons that show spontaneous regeneration. Inhibition of G3BP1 by expression of its acidic or 'B-domain' accelerates axon regeneration after nerve injury bringing a potential therapeutic intervention to promote neural repair in the peripheral nervous system. Here, we asked if G3BP1 inhibition is a viable strategy to promote regeneration in the injured mammalian central nervous system where axons do not regenerate spontaneously.

Analysis and benchmarking of small and large genomic variants across tandem repeats.

Tandem repeats (TRs) are highly polymorphic in the human genome, have thousands of associated molecular traits and are linked to over 60 disease phenotypes. However, they are often excluded from at-scale studies because of challenges with variant calling and representation, as well as a lack of a genome-wide standard. Here, to promote the development of TR methods, we created a catalog of TR regions and explored TR properties across 86 haplotype-resolved long-read human assemblies.

Does engagement matter? The impact of patient and community engagement on implementation of cardiovascular health materials in primary care settings.

Background: Engaging patients and community members in healthcare implementation, research and evaluation has become more popular over the past two decades. Despite the growing interest in patient engagement, there is scant evidence of its impact and importance. Boot Camp Translation (BCT) is one evidence-based method of engaging communities in research.

P2X receptor-dependent increase in endocannabinoid 2-arachidonoyl glycerol production by neuronal cells in culture: Dynamics and mechanism.

Background And Purpose: Neurotransmission and neuroinflammation are controlled by local increases in both extracellular ATP and the endocannabinoid 2-arachidonoyl glycerol (2-AG). While it is known that extracellular ATP stimulates 2-AG production in cells in culture, the dynamics and molecular mechanisms that underlie this response remain poorly understood. Detection of real-time changes in eCB levels with the genetically encoded sensor, GRAB, can address this shortfall.

The phospholipids cardiolipin and phosphatidylethanolamine differentially regulate MDC biogenesis.

Cells utilize multiple mechanisms to maintain mitochondrial homeostasis. We recently characterized a pathway that remodels mitochondria in response to metabolic alterations and protein overload stress. This remodeling occurs via the formation of large membranous structures from the mitochondrial outer membrane called mitochondrial-derived compartments (MDCs), which are eventually released from mitochondria and degraded.

Optimal omegas - barriers and novel methods to narrow omega-3 gaps. A narrative review.

Dietary intakes of omega-3 long chain polyunsaturated fatty acids (O3LC-PUFAs) such as eicosapentaenoic and docosahexaenoic acid are central to development and health across the life course. O3LC-PUFAs have been linked to neurological development, maternal and child health and the etiology of certain non-communicable diseases including age-related cognitive decline, cardiovascular disease, and diabetes. However, dietary inadequacies exist in the United Kingdom and on a wider global scale.

Exploring metformin monotherapy response in Type-2 diabetes: Computational insights through clinical, genomic, and proteomic markers using machine learning algorithms.

Background: In 2016, the UK had 4.5 million people with diabetes, predominantly Type-2 Diabetes Mellitus (T2DM). The NHS allocates £10 billion (9% of its budget) to manage diabetes.

Analysis of SARS-CoV-2 antibody seroprevalence in Northern Ireland during 2020-2021.

Background: With the spread of SARS-CoV-2 impacting upon public health directly and socioeconomically, further information was required to inform policy decisions designed to limit virus spread during the pandemic. This study sought to contribute to serosurveillance work within Northern Ireland to track SARS-CoV-2 progression and guide health strategy.

Methods: Sera/plasma samples from clinical biochemistry laboratories were analysed for anti-SARS-CoV-2 antibodies.