Palmitoylation and regulation of potassium dependent sodium/calcium exchangers (NCKX).

Cellular Ca2+ homeostasis is critical for normal cell physiology and is regulated by several mechanisms. Two major players in intracellular Ca2+ homeostasis in multiple tissues belong to SLC8 (Na+/Ca2+ exchangers (NCXs); NCX1-3) and SLC24 (K+ dependent Na+/Ca2+ exchangers (NCKXs); NCKX1-5) families. It has been established that NCXs and NCKX4 are palmitoylated, and that palmitoylation promotes NCX1 inactivation.

Perspectives on the Regional Strategy for Implementation of National Action Plans on Antimicrobial Resistance in the WHO African Region.

The WHO Regional Office for Africa developed a Member States (MS)-endorsed regional strategy to fast-track the implementation of MS' national action plans (NAP) on Antimicrobial resistance (AMR). This study explored the perspectives of AMR's national focal points in MS on the implementation of the priority interventions of the regional strategy in their countries. An online survey consisting of ratings and discussions covering the implementation of the six priority interventions was conducted.

SUMOylation of cardiac myosin binding protein-C reduces its phosphorylation and results in impaired relaxation following treatment with isoprenaline.

Systolic and diastolic functions are coordinated in the heart by myofilament proteins that influence force of contraction and calcium sensitivity. Fine control of these processes is afforded by a variety of post-translation modifications that occur on specific proteins at different times during each heartbeat. Cardiac myosin binding protein-C is a sarcomeric accessory protein whose function is to interact transiently with actin, tropomyosin and myosin.

Collagen IV deficiency causes hypertrophic remodeling and endothelium-dependent hyperpolarization in small vessel disease with intracerebral hemorrhage.

Background: Genetic variants in COL4A1 and COL4A2 (encoding collagen IV alpha chain 1/2) occur in genetic and sporadic forms of cerebral small vessel disease (CSVD), a leading cause of stroke, dementia and intracerebral haemorrhage (ICH). However, the molecular mechanisms of CSVD with ICH and COL4A1/COL4A2 variants remain obscure.

Methods: Vascular function and molecular investigations in mice with a Col4a1 missense mutation and heterozygous Col4a2 knock-out mice were combined with analysis of human brain endothelial cells harboring COL4A1/COL4A2 mutations, and brain tissue of patients with sporadic CSVD with ICH.

Antimicrobial Resistance in the WHO African Region: A Systematic Literature Review 2016-2020.

Antimicrobial resistance (AMR) is a significant global public health threat. This review presents the most recent in-depth review of the situation of the main AMR types in relation to the most commonly prescribed antibiotics in the World Health Organization (WHO) African Region. Underlying genes of resistance have been analyzed where possible.

Surveillance of Antimicrobial Resistance in the ECOWAS Region: Setting the Scene for Critical Interventions Needed.

Antimicrobial resistance poses a significant challenge to public health globally, leading to increased morbidity and mortality. AMR surveillance involves the systematic collection, analysis, and interpretation of data on the occurrence and distribution of AMR in humans, animals, and the environment for action. The West African Health Organization, part of the Economic Community of West African States (ECOWAS), is committed to addressing AMR in the region.

Acquired Risk Factors that Influence Risk for Dementia and Possibly Alzheimer Disease.

Various medicinal agents aimed at improving Alzheimer disease (AD) include cholinesterase inhibitors, memantine, aducanumab, and antioxidants. These medications are typically prescribed once AD is diagnosed in the clinical setting in order to slow progression. Though initiating treatment after being diagnosed with AD is important, significance should be placed on recognizing known acquired risk factors in order to potentially decrease the likelihood of developing dementia and perhaps specifically AD.

Elevated Na is a dynamic and reversible modulator of mitochondrial metabolism in the heart.

Elevated intracellular sodium Na adversely affects mitochondrial metabolism and is a common feature of heart failure. The reversibility of acute Na induced metabolic changes is evaluated in Langendorff perfused rat hearts using the Na/K ATPase inhibitor ouabain and the myosin-uncoupler para-aminoblebbistatin to maintain constant energetic demand. Elevated Na decreases Gibb's free energy of ATP hydrolysis, increases the TCA cycle intermediates succinate and fumarate, decreases ETC activity at Complexes I, II and III, and causes a redox shift of CoQ to CoQH, which are all reversed on lowering Na to baseline levels.

Rise of palmitoylation: A new trick to tune NCX1 activity.

The cardiac Na+/Ca2+ Exchanger (NCX1) controls transmembrane calcium flux in numerous tissues. The only reversible post-translational modification established to regulate NCX1 is palmitoylation, which alters the ability of the exchanger to inactivate. Palmitoylation creates a binding site for the endogenous XIP domain, a region of the NCX1 intracellular loop established to inactivate NCX1.

Targeted degradation of zDHHC-PATs decreases substrate S-palmitoylation.

Reversible S-palmitoylation of protein cysteines, catalysed by a family of integral membrane zDHHC-motif containing palmitoyl acyl transferases (zDHHC-PATs), controls the localisation, activity, and interactions of numerous integral and peripheral membrane proteins. There are compelling reasons to want to inhibit the activity of individual zDHHC-PATs in both the laboratory and the clinic, but the specificity of existing tools is poor. Given the extensive conservation of the zDHHC-PAT active site, development of isoform-specific competitive inhibitors is highly challenging.

Monitoring progress on Antimicrobial Resistance (AMR) response in the World Health Organization African region: Insights from the Tracking AMR Country Self-Assessment Survey (TrACSS) 2021 results for the human health sector.

Antimicrobial resistance (AMR) is a major 21st century global health challenge. The WHO African Region Member States committed to develop and implement multisectoral national action plans (NAPs) that address AMR, in line with the Global Action Plan on AMR (GAP). The aim of this paper is to present the progress of AMR response in the WHO African Region based on the annual Tracking AMR Country Self-Assessment Survey (TrACSS), with a focus on human health indicators.

Cysteine post-translational modifications regulate protein interactions of caveolin-3.

Caveolae are small flask-shaped invaginations of the surface membrane which are proposed to recruit and co-localize signaling molecules. The distinctive caveolar shape is achieved by the oligomeric structural protein caveolin, of which three isoforms exist. Aside from the finding that caveolin-3 is specifically expressed in muscle, functional differences between the caveolin isoforms have not been rigorously investigated.

Marine turtles as bio-indicators of plastic pollution in the eastern Mediterranean.

The loggerhead turtle (Caretta caretta) has been suggested as a bio-indicator species for plastic pollution. However, detailed investigations in the eastern Mediterranean are limited. Here, we present data from loggerhead turtles (2012-2022; n = 131) of which 42.

Glutathione-dependent depalmitoylation of phospholemman by peroxiredoxin 6.

Phospholemman (PLM) regulates the cardiac sodium pump: PLM phosphorylation activates the pump whereas PLM palmitoylation inhibits its activity. Here, we show that the anti-oxidant protein peroxiredoxin 6 (Prdx6) interacts with and depalmitoylates PLM in a glutathione-dependent manner. Glutathione loading cells acutely reduce PLM palmitoylation; glutathione depletion significantly increases PLM palmitoylation.

Education and Awareness on Antimicrobial Resistance in the WHO African Region: A Systematic Review.

This review documents the status of AMR education and awareness in the WHO African region, as well as specific initiatives by its member states in implementing education and awareness interventions, as a strategic objective of the Global Action Plan on AMR, i.e., improve knowledge and understanding on AMR through effective communication, education, and training.

Palmitoylation regulates the magnitude of HCN4-mediated currents in mammalian cells.

The sinoatrial node (SAN) and subsidiary pacemakers in the cardiac conduction system generate spontaneous electrical activity which is indispensable for electrical and therefore contractile function of the heart. The hyperpolarisation-activated cyclic nucleotide-gated channel HCN4 is responsible for genesis of the pacemaker "funny" current during diastolic depolarisation. S-palmitoylation, the reversible conjugation of the fatty acid palmitate to protein cysteine sulfhydryls, regulates the activity of key cardiac Na and Ca handling proteins, influencing their membrane microdomain localisation and function.

Priorities for Mediterranean marine turtle conservation and management in the face of climate change.

As climate-related impacts threaten marine biodiversity globally, it is important to adjust conservation efforts to mitigate the effects of climate change. Translating scientific knowledge into practical management, however, is often complicated due to resource, economic and policy constraints, generating a knowledge-action gap. To develop potential solutions for marine turtle conservation, we explored the perceptions of key actors across 18 countries in the Mediterranean.

Polypharmacy in Older Adults: A Case Study.

Polypharmacy is defined as concurrent use of multiple drugs for one or more conditions. The occurrence of polypharmacy in vulnerable populations, particularly the elderly, is frequent. Increased incidents of adverse drug reactions and drug-drug interactions plus high costs are not offset by a noticeable improvement in outcome.

Palmitoylation of the pore-forming subunit of Ca(v)1.2 controls channel voltage sensitivity and calcium transients in cardiac myocytes.

Mammalian voltage-activated L-type Ca channels, such as Ca(v)1.2, control transmembrane Ca fluxes in numerous excitable tissues. Here, we report that the pore-forming α1C subunit of Ca(v)1.

Altered Cortical Palmitoylation Induces Widespread Molecular Disturbances in Parkinson's Disease.

The relationship between Parkinson's disease (PD), the second-most common neurodegenerative disease after Alzheimer's disease, and palmitoylation, a post-translational lipid modification, is not well understood. In this study, to better understand the role of protein palmitoylation in PD and the pathways altered in this disease, we analyzed the differential palmitoyl proteome (palmitome) in the cerebral cortex of PD patients compared to controls ( = 4 per group). Data-mining of the cortical palmitome from PD patients and controls allowed us to: (i) detect a set of 150 proteins with altered palmitoylation in PD subjects in comparison with controls; (ii) describe the biological pathways and targets predicted to be altered by these palmitoylation changes; and (iii) depict the overlap between the differential palmitome identified in our study with protein interactomes of the PD-linked proteins α-synuclein, LRRK2, DJ-1, PINK1, GBA and UCHL1.

Dynamic but discordant alterations in zDHHC5 expression and palmitoylation of its substrates in cardiac pathologies.

S-palmitoylation is an essential lipid modification catalysed by zDHHC-palmitoyl acyltransferases that regulates the localisation and activity of substrates in every class of protein and tissue investigated to date. In the heart, S-palmitoylation regulates sodium-calcium exchanger (NCX1) inactivation, phospholemman (PLM) inhibition of the Na/K ATPase, Nav1.5 influence on membrane excitability and membrane localisation of heterotrimeric G-proteins.

Global Antimicrobial Resistance and Use Surveillance System on the African continent: Early implementation 2017-2019.

Background: Antimicrobial resistance (AMR) is becoming a critical public health issue globally. The World Health Organization launched the Global Antimicrobial Resistance and Use Surveillance System (GLASS) to support the strengthening of the AMR evidence base.

Objective: The article describes the evolution of national AMR surveillance systems and AMR data reporting of countries in the African continent between 2017 and 2019, and the constraints, perceived impact and value of the participation in GLASS.

National action plan on antimicrobial resistance: An evaluation of implementation in the World Health Organization Africa region.

In line with global instruments, within the last five years, two-thirds of all countries in the WHO Africa Region (WHO AFR) have developed a National Action Plan (NAP) on Antimicrobial Resistance (AMR). We sought to evaluate progress made across the countries implementing NAP for effective response to AMR. A semi-structured survey tool was administered to obtain information from national focal persons on the implementation of strategic elements of NAP on AMR.