Allostery is a form of protein regulation, where ligands that bind sites located apart from the active site can modify the activity of the protein. The molecular mechanisms of allostery have been extensively studied, because allosteric sites are less conserved than active sites, and drugs targeting them are more specific than drugs binding the active sites. Here we quantify the importance of al...

Background Although a rapid rise in left atrial pressure during exertion is considered pathognomonic of heart failure with preserved ejection fraction (HFpEF), the fundamental circulatory determinants of this response are not clear, impacting upon the development of more effective therapies. We aimed to comprehensively describe the circulatory mechanics of patients with HFpEF at rest and during...

CRISPR/Cas9 technology has revolutionized gene editing and fast tracked our capacity to manipulate genes of interest for the benefit of both research and therapeutic applications. Whilst many advances have, and continue to be made in this area, perhaps the most utilized technology to date has been the generation of knockout cells, tissues and animals. The advantages of this technology are many ...

The extracellular vesicle (EV) surface proteome (surfaceome) acts as a fundamental signalling gateway by bridging intra- and extracellular signalling networks, dictates EVs' capacity to communicate and interact with their environment, and is a source of potential disease biomarkers and therapeutic targets. However, our understanding of surface protein composition of large EVs (L-EVs, 100-800 nm...

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G protein-coupled receptors (GPCRs) can selectively bind to many types of ligands, ranging from light-sensitive compounds, ions, hormones, pheromones and neurotransmitters, modulating cell physiology. Considering their role in many essential cellular processes, they are one of the most targeted protein families, with over a third of all approved drugs modulating GPCR signalling. Despite this, t...

Heart failure represents the end point of a variety of cardiovascular diseases. It is a growing health burden and a leading cause of death worldwide. To date, limited treatment options exist for the treatment of heart failure, but exercise has been well-established as one of the few safe and effective interventions, leading to improved outcomes in patients. However, a lack of patient adherence ...

CRP is an important mediator of the inflammatory response. Pro-inflammatory CRP effects are mediated by pCRP* and mCRP, dissociation products of the native pCRP. The concentration of pCRP during inflammation may rise up to concentrations 1000-fold from baseline. By prevention of the conformational change from pCRP to pCRP*, pro-inflammatory immune responses can be inhibited and local tissue dam...

Adipose-tissue-resident macrophages (ATMs) maintain metabolic homeostasis but also contribute to obesity-induced adipose tissue inflammation and metabolic dysfunction. Central to these contrasting effects of ATMs on metabolic homeostasis is the interaction of macrophages with fatty acids. Fatty acid levels are increased within adipose tissue in various pathological and physiological conditions,...

Older adults with obesity spend the majority of their waking hours sedentary. Given substantial barriers to regular physical activity in this population, approaches to reduce sedentary time could be an effective health promotion strategy. We present the protocol of a randomized controlled trial to reduce sitting time in older adults with a body mass index of 30 kg/m or above. Participants (N = ...

To provide an overview of the associations between elevated blood pressure and lipoprotein (a) and possible causal links, as well as data on the prevalence of elevated lipoprotein (a) in a cohort of hypertensive patients.Elevated lipoprotein (a) is now considered to be an independent and causal risk factor for atherosclerotic cardiovascular disease and calcific aortic valve disease. Despite thi...

Majority of patients with hypertension and chronic kidney disease (CKD) undergoing renal denervation (RDN) are maintained on antihypertensive medication. However, RDN may impair compensatory responses to hypotension induced by blood loss. Therefore, continuation of antihypertensive medications in denervated patients may exacerbate hypotensive episodes. This study examined whether antihypertensi...

Population ageing and urbanisation are global phenomena that call for an understanding of the impacts of features of the urban environment on older adults' cognitive function. Because neighbourhood characteristics that can potentially have opposite effects on cognitive function are interdependent, they need to be considered in conjunction. Using data from an Australian national sample of 4141 a...

Antimicrobial resistance develops following the accrual of mutations in the bacterial genome, and may variably impact organism fitness and hence, transmission risk. Classical representation of tuberculosis (TB) dynamics using a single or two strain (DS/MDR-TB) model typically does not capture elements of this important aspect of TB epidemiology. To understand and estimate the likelihood of resi...

A hypertensive response to submaximal exercise is associated with cardiovascular disease but this relationship is influenced by functional capacity. Spironolactone improves functional capacity, which could mask treatment effects on exercise blood pressure. This study sought to examine this hypothesis.Retrospective analysis of a randomized clinical trial.102 participants (54 ± 9 years; 52% male)...

Recent research has demonstrated discrepancies in care post-ST-elevation myocardial infarction (STEMI), showing that women often have delays in time to percutaneous coronary intervention (PCI) and are less often prescribed evidence-based medications for secondary prevention. This single-centre study evaluated gender differences in management and local prescribing patterns of STEMI patients on d...

Ambulatory blood pressure monitoring (ABPM) is usually reported in descriptive values such as circadian averages and standard deviations. Making use of the original, individual blood pressure measurements may be advantageous, particularly for research purposes, as this increases the flexibility of the analytical process, enables alternative statistical analyses and provide novel insights. Here ...