Molecular basis of human angiotensin-1 converting enzyme inhibition by a series of diprolyl-derived compounds.

Angiotensin-1-converting enzyme (ACE) is a zinc-dependent carboxypeptidase of therapeutic interest for the treatment of hypertension, inflammation and fibrosis. It consists of two homologous N and C catalytic domains, nACE and cACE, respectively. Unfortunately, the current clinically available ACE inhibitors produce undesirable side effects due to the nonselective inhibition of these domains.

Functional implications of unusual NOS and SONOS covalent linkages found in proteins.

The tertiary and quaternary structures of many proteins are stabilized by strong covalent forces, of which disulfide bonds are the most well known. A new type of intramolecular and intermolecular covalent bond has been recently reported, consisting of the Lys and Cys side-chains linked by an oxygen atom (NOS). These post-translational modifications are widely distributed amongst proteins, and are formed under oxidative conditions.

Advances in the structural basis for angiotensin-1 converting enzyme (ACE) inhibitors.

Human somatic angiotensin-converting enzyme (ACE) is a key zinc metallopeptidase that plays a pivotal role in the renin-angiotensin-aldosterone system (RAAS) by regulating blood pressure and electrolyte balance. Inhibition of ACE is a cornerstone in the management of hypertension, cardiovascular diseases, and renal disorders. Recent advances in structural biology techniques have provided invaluable insights into the molecular mechanisms underlying ACE inhibition, facilitating the design and development of more effective therapeutic agents.

Structural insights into the inhibitory mechanism of angiotensin-I-converting enzyme by the lactotripeptides IPP and VPP.

Human somatic angiotensin-1-converting enzyme (sACE) is composed of a catalytic N-(nACE) and C-domain (cACE) of similar size with different substrate specificities. It is involved in the regulation of blood pressure by converting angiotensin I to the vasoconstrictor angiotensin II and has been a major focus in the development of therapeutics for hypertension. Bioactive peptides from various sources, including milk, have been identified as natural ACE inhibitors.

Crystal Structure of the Catalytic Domain of a Botulinum Neurotoxin Homologue from : Potential Insights into Substrate Recognition.

neurotoxins (BoNTs) are the most potent toxins known, causing the deadly disease botulism. They function through Zn-dependent endopeptidase cleavage of SNARE (soluble N-ethylmaleimide-sensitive factor attachment protein receptor) proteins, preventing vesicular fusion and subsequent neurotransmitter release from motor neurons. Several serotypes of BoNTs produced by (BoNT/A-/G and/X) have been well-characterised over the years.

A Molecular Analysis of the Aminopeptidase P-Related Domain of PID-5 from .

A novel protein, PID-5, has been shown to be a requirement for germline immortality and has recently been implicated in RNA-induced epigenetic silencing in the embryo. Importantly, it has been shown to contain both an eTudor and aminopeptidase P-related domain. However, the silencing mechanism has not yet been fully characterised.

A Comprehensive Structural Analysis of Neurotoxin A Cell-Binding Domain from Different Subtypes.

Botulinum neurotoxins (BoNTs) cause flaccid neuromuscular paralysis by cleaving one of the SNARE (soluble -ethylmaleimide-sensitive factor attachment protein receptor) complex proteins. BoNTs display high affinity and specificity for neuromuscular junctions, making them one of the most potent neurotoxins known to date. There are seven serologically distinct BoNTs (serotypes BoNT/A to BoNT/G) which can be further divided into subtypes (e.

Crystal Structures of the Neurotoxin A6 Cell Binding Domain Alone and in Complex with GD1a Reveal Significant Conformational Flexibility.

neurotoxin A (BoNT/A) targets the soluble -ethylmaleimide-sensitive factor attachment protein receptor (SNARE) complex, by cleaving synaptosomal-associated protein of 25 kDa size (). Cleavage of SNAP-25 results in flaccid paralysis due to repression of synaptic transmission at the neuromuscular junction. This activity has been exploited to treat a range of diseases associated with hypersecretion of neurotransmitters, with formulations of BoNT/A commercially available as therapeutics.

Structural Features of Neurotoxin Subtype A2 Cell Binding Domain.

Botulinum neurotoxins (BoNT) are a group of clostridial toxins that cause the potentially fatal neuroparalytic disease botulism. Although highly toxic, BoNTs are utilized as therapeutics to treat a range of neuromuscular conditions. Several serotypes (BoNT/A-/G, /X) have been identified with vastly differing toxicological profiles.

Crystal Structures of Botulinum Neurotoxin Subtypes A4 and A5 Cell Binding Domains in Complex with Receptor Ganglioside.

Botulinum neurotoxins (BoNT) cause the potentially fatal neuroparalytic disease botulism that arises due to proteolysis of a SNARE protein. Each BoNT is comprised of three domains: a cell binding domain (H), a translocation domain (H), and a catalytic (Zn endopeptidase) domain (LC). The H is responsible for neuronal specificity by targeting both a protein and ganglioside receptor at the neuromuscular junction.

Developmental changes in cardiac expression of KCNQ1 and SCN5A spliceoforms: Implications for sudden unexpected infant death.

Background: Sudden unexpected infant death (SUID) occurs unpredictably and remains unexplained after scene investigation and autopsy. Approximately 1 in 7 cases of SUID can be related to a cardiac cause, and developmental regulation of cardiac ion channel genes may contribute to SUID.

Objective: The goal of this study was to investigate the developmental changes in the spliceoforms of SCN5A and KCNQ1, 2 genes implicated in SUID.

Changes to cigarette packaging influence US consumers' choices: Results of two discrete-choice experiments to inform regulation.

Introduction: While plain packaging of tobacco products has emerged as a policy intervention to reduce smoking, regulators in the US have limited ability to implement plain packaging. We sought to identify the impact of subtle changes to cigarette packaging (Study 1) and how packaging design influenced participant choices based on appeal, harm, and style (Study 2).

Methods: We conducted two discrete-choice experiments with US adult smokers online in 2018.

Home medicines reviews: a national survey of Australian accredited pharmacists' health service time investment.

Background: In Australia, polypharmacy and medication-related problems are prevalent in the community. Therefore, medicines safety initiatives such as the Home Medicines Review (HMR) service are critical to health care provision. While the evidence continues to expand around HMR service, little is known of accredited pharmacists' experiences of HMR time investment.

Crystal structure of botulinum neurotoxin subtype A3 cell binding domain in complex with GD1a co-receptor ganglioside.

Botulinum neurotoxins (BoNTs) are one of the most toxic proteins known to humans. Their molecular structure is comprised of three essential domains-a cell binding domain (H ), translocation domain and catalytic domain (light chain) . The H domain facilitates the highly specific binding of BoNTs to the neuronal membrane via a dual-receptor complex involving a protein receptor and a ganglioside.

Assessing the Potential Impact of Cigarette Packs Designed for Lesbian, Gay, Bisexual, and Transgender Adults: A Randomized Experiment to Inform U.S. Regulation, 2018.

The Food and Drug Administration (FDA) can regulate the introduction of new tobacco products and some changes to existing products. Cigarette packs have been used as a marketing tool to target specific groups and priority populations. Research has shown that sexual and gender minority (SGM) adults are substantially more likely to use tobacco products than their straight and cisgender counterparts.

Using the big five inventory to evaluate the personality traits of Australian pharmacists.

Objectives: Pharmacist personality traits may explain the incomplete uptake of extended scope pharmacy practice roles. The objective of this study was to explore the personality traits of Australian pharmacists using the Big Five Inventory (BFI).

Methods: A cross-sectional survey of Australian pharmacists was undertaken.

Pharmacist Compliance With Therapeutic Guidelines on Diagnosis and Treatment Provision.

Importance: Misuse and overselling of over-the-counter pharmaceuticals poses a major burden on both private and public health expenditures.

Objective: To seek evidence on whether over-the-counter medication dispensing behavior complies or conflicts with the protocols indicated in practice standards and guidelines of a national professional pharmacy organization.

Design, Setting, And Participants: This quality improvement study was undertaken in 205 pharmacies in the wider Brisbane, Australia, area.

Evolving IQOS packaging designs change perceptions of product appeal, uniqueness, quality and safety: a randomised experiment, 2018, USA.

Background: Globally, the tobacco industry is promoting heated tobacco products. These products may represent a strategy to promote dual use of tobacco products. One product, IQOS from Philip Morris International, is being proposed in the USA for marketing as a less harmful product.

Health professional beliefs, knowledge, and concerns surrounding medicinal cannabis - A systematic review.

Background: The number of jurisdictions allowing access to medicinal cannabis has been steadily increasing since the state of California introduced legislation in 1996. Although there is a high degree of legislative heterogeneity across jurisdictions, the involvement of a health professional is common among all. This places health professionals at the forefront of therapy, yet no systematic review of literature has offered insight into the beliefs, knowledge, and concerns of health professionals regarding medicinal cannabis.

"The Packaging Is Very Inviting and Makes Smokers Feel Like They're More Safe": The Meanings of Natural American Spirit Cigarette Pack Design to Adult Smokers.

Background/aims: The aim of this investigation was to identify which design elements on Natural American Spirit packs are salient to (i.e., noticed by) U.

What can pharmacists do in general practice? A pilot trial.

Background And Objectives: Non-dispensing pharmacists are being suggested as a useful addition to the workforce in general practice. The aim of this study was to describe the activities of three general practice pharmacists over six months in a pilot trial.

Method: Three general practices integrated a part-time (15.

Stakeholder perspectives about general practice pharmacists in the Australian Capital Territory: a qualitative pilot study.

Previous studies have found that integrating non-dispensing pharmacists in general practice may improve patient safety, improve patient outcomes, deliver health system efficiencies and generate savings. However, the employment of pharmacists in general practice is not common in Australia. A naturalistic study was conducted in the Australian Capital Territory with three general practices, each employing a part-time pharmacist for 12 months.

Qualitative assessment of a Context of Consumption Framework to inform regulation of cigarette pack design in the U.S.

Introduction: Researchers and regulators need to know how changes to cigarette packages can influence population health. We sought to advance research on the role of cigarette packaging by assessing a theory-informed framework from the fields of design and consumer research. The selected Context of Consumption Framework posits cognitive, affective, and behavioral responses to visual design.

Is the cigarette pack just a wrapper or a characteristic of the product itself? A qualitative study of adult smokers to inform U.S. regulations.

Purpose: In the U.S., tobacco products are now regulated by the Food and Drug Administration (FDA).

Why does the need for medication become a barrier to breastfeeding? A narrative review.

Problem: The need for medication during lactation can contribute to the early cessation of breastfeeding.

Background: Breastfeeding women may require medication for acute or chronic health conditions. For some women this need for medication can become a barrier to breastfeeding; this is despite the fact that the majority of medications are considered to be compatible with lactation.