Deep underground metagenome-assembled genomes from hydrothermal spring.

We report 19 metagenome-assembled genomes from a deep underground microbial community found in mineralized hydrothermal spring in the Baksan Neutrino Observatory tunnel. The community is predominantly occupied by members of Pseudomonadota (Gamma-, Beta-, and Alphaproteobacteria), Planctomycetota, Myxococcota, Nitrospirota, Cyanobacteria, Gemmatimonadota, and Armatimonadota.

Reprogramming of cardiac phosphoproteome, proteome, and transcriptome confers resilience to chronic adenylyl cyclase-driven stress.

Our prior study (Tarasov et al., 2022) discovered that numerous adaptive mechanisms emerge in response to cardiac-specific overexpression of adenylyl cyclase type 8 (TGAC8) which included overexpression of a large number of proteins. Here, we conducted an unbiased phosphoproteomics analysis in order to determine the role of altered protein phosphorylation in the adaptive heart performance and protection profile of adult TGAC8 left ventricle (LV) at 3-4 months of age, and integrated the phosphoproteome with transcriptome and proteome.

Transcriptome of Left Ventricle and Sinoatrial Node in Young and Old C57 Mice.

Advancing age is the most important risk factor for cardiovascular diseases (CVDs). Two types of cells, within the heart pacemaker, sinoatrial node (SAN), and within the left ventricle (LV), control two crucial characteristics of heart function, heart beat rate and contraction strength. As age advances, the heart's structure becomes remodeled, and SAN and LV cell functions deteriorate, thus increasing the risk for CVDs.

Enhanced Myocardial Adenylyl Cyclase Activity Alters Heart-Brain Communication.

Background: The central nervous system's influence on cardiac function is well described; however, direct evidence for signaling from heart to brain remains sparse. Mice with cardiac-selective overexpression of adenylyl cyclase type 8 (TGAC8) display elevated heart rate/contractility and altered neuroautonomic surveillance.

Objectives: In this study the authors tested whether elevated adenylyl cyclase type 8-dependent signaling at the cardiac cell level affects brain activity and behavior.

Modification of Some Structural and Functional Parameters of Living Culture of as the Result of Selenium Nanoparticle Biosynthesis.

Selenium nanoparticles are attracting the attention of researchers due to their multiple applications, including medicine. The biosynthesis of selenium nanoparticles has become particularly important due to the environmentally friendly character of the process and special properties of the obtained particles. The possibility of performing the biosynthesis of selenium nanoparticles via the living culture of starting from sodium selenite was studied.

A remarkable adaptive paradigm of heart performance and protection emerges in response to marked cardiac-specific overexpression of ADCY8.

Adult (3 month) mice with cardiac-specific overexpression of adenylyl cyclase (AC) type VIII (TG) adapt to an increased cAMP-induced cardiac workload (~30% increases in heart rate, ejection fraction and cardiac output) for up to a year without signs of heart failure or excessive mortality. Here, we show classical cardiac hypertrophy markers were absent in TG, and that total left ventricular (LV) mass was not increased: a reduced LV cavity volume in TG was encased by thicker LV walls harboring an increased number of small cardiac myocytes, and a network of small interstitial proliferative non-cardiac myocytes compared to wild type (WT) littermates; Protein synthesis, proteosome activity, and autophagy were enhanced in TG vs WT, and Nrf-2, Hsp90α, and ACC2 protein levels were increased. Despite increased energy demands in vivo LV ATP and phosphocreatine levels in TG did not differ from WT.

Cytobacillus pseudoceanisediminis sp. nov., A Novel Facultative Methylotrophic Bacterium with High Heavy Metal Resistance Isolated from the Deep Underground Saline Spring.

In this study, we present the characterization of the BNO1 bacterial strain isolated from the deep subsurface saline spring at the Baksan Neutrino Observatory INR RAS (Kabardino-Balkaria, Russia). The complete genome sequence of the strain BNO1 is 5,347,902 bp, with a GC content 41 and 49%. The cell wall peptidoglycan contains meso-diaminopimelic acid.

Proteomic Landscape and Deduced Functions of the Cardiac 14-3-3 Protein Interactome.

: The 14-3-3 protein family is known to interact with many proteins in non-cardiac cell types to regulate multiple signaling pathways, particularly those relating to energy and protein homeostasis; and the 14-3-3 network is a therapeutic target of critical metabolic and proteostatic signaling in cancer and neurological diseases. Although the heart is critically sensitive to nutrient and energy alterations, and multiple signaling pathways coordinate to maintain the cardiac cell homeostasis, neither the structure of cardiac 14-3-3 protein interactome, nor potential functional roles of 14-3-3 protein-protein interactions (PPIs) in heart has been explored. : To establish the comprehensive landscape and characterize the functional role of cardiac 14-3-3 PPIs.

Phosphoprotein Phosphatase 1 but Not 2A Activity Modulates Coupled-Clock Mechanisms to Impact on Intrinsic Automaticity of Sinoatrial Nodal Pacemaker Cells.

Spontaneous AP (action potential) firing of sinoatrial nodal cells (SANC) is critically dependent on protein kinase A (PKA) and Ca/calmodulin-dependent protein kinase II (CaMKII)-dependent protein phosphorylation, which are required for the generation of spontaneous, diastolic local Ca releases (LCRs). Although phosphoprotein phosphatases (PP) regulate protein phosphorylation, the expression level of PPs and phosphatase inhibitors in SANC and the impact of phosphatase inhibition on the spontaneous LCRs and other players of the oscillatory coupled-clock system is unknown. Here, we show that rabbit SANC express both PP1, PP2A, and endogenous PP inhibitors I-1 (PPI-1), dopamine and cyclic adenosine 3',5'-monophosphate (cAMP)-regulated phosphoprotein (DARPP-32), kinase C-enhanced PP1 inhibitor (KEPI).

Self-Similar Synchronization of Calcium and Membrane Potential Transitions During Action Potential Cycles Predict Heart Rate Across Species.

Objectives: The purpose of this study was to discover regulatory universal mechanisms of normal automaticity in sinoatrial nodal (SAN) pacemaker cells that are self-similar across species.

Background: Translation of knowledge of SAN automaticity gleaned from animal studies to human dysrhythmias (e.g.

Multi-ancestry GWAS of the electrocardiographic PR interval identifies 202 loci underlying cardiac conduction.

The electrocardiographic PR interval reflects atrioventricular conduction, and is associated with conduction abnormalities, pacemaker implantation, atrial fibrillation (AF), and cardiovascular mortality. Here we report a multi-ancestry (N = 293,051) genome-wide association meta-analysis for the PR interval, discovering 202 loci of which 141 have not previously been reported. Variants at identified loci increase the percentage of heritability explained, from 33.

Effects of Calcium, Magnesium, and Potassium Concentrations on Ventricular Repolarization in Unselected Individuals.

Background: Subclinical changes on the electrocardiogram are risk factors for cardiovascular mortality. Recognition and knowledge of electrolyte associations in cardiac electrophysiology are based on only in vitro models and observations in patients with severe medical conditions.

Objectives: This study sought to investigate associations between serum electrolyte concentrations and changes in cardiac electrophysiology in the general population.

PR interval genome-wide association meta-analysis identifies 50 loci associated with atrial and atrioventricular electrical activity.

Electrocardiographic PR interval measures atrio-ventricular depolarization and conduction, and abnormal PR interval is a risk factor for atrial fibrillation and heart block. Our genome-wide association study of over 92,000 European-descent individuals identifies 44 PR interval loci (34 novel). Examination of these loci reveals known and previously not-yet-reported biological processes involved in cardiac atrial electrical activity.

A coupled-clock system drives the automaticity of human sinoatrial nodal pacemaker cells.

The spontaneous rhythmic action potentials generated by the sinoatrial node (SAN), the primary pacemaker in the heart, dictate the regular and optimal cardiac contractions that pump blood around the body. Although the heart rate of humans is substantially slower than that of smaller experimental animals, current perspectives on the biophysical mechanisms underlying the automaticity of sinoatrial nodal pacemaker cells (SANCs) have been gleaned largely from studies of animal hearts. Using human SANCs, we demonstrated that spontaneous rhythmic local Ca releases generated by a Ca clock were coupled to electrogenic surface membrane molecules (the M clock) to trigger rhythmic action potentials, and that Ca-cAMP-protein kinase A (PKA) signaling regulated clock coupling.

Mammalian γ2 AMPK regulates intrinsic heart rate.

AMPK is a conserved serine/threonine kinase whose activity maintains cellular energy homeostasis. Eukaryotic AMPK exists as αβγ complexes, whose regulatory γ subunit confers energy sensor function by binding adenine nucleotides. Humans bearing activating mutations in the γ2 subunit exhibit a phenotype including unexplained slowing of heart rate (bradycardia).

An LC-MS/MS based candidate reference method for the quantification of carbamazepine in human serum.

A validated LC-MS/MS-based candidate reference measurement procedure for the quantification of carbamazepine is presented in order to be used for standardization and harmonization of routine assays applied for therapeutic drug monitoring. Sample preparation was based on protein precipitation using acetonitrile followed by sample dilution. Since the previously listed certified reference material (CRM) SRM 1599 (anticonvulsant drug level assay standard) is no longer available, an ISO certified calibration material was used in this assay.

An LC-MS/MS based candidate reference method for the quantification of total gentamicin in human serum and plasma using NMR characterized calibrator material.

Background: Accurate measurement of gentamicin concentration in serum and plasma is required for therapeutic drug monitoring to ensure appropriate treatment of patients. In this work, we present a validated LC-MS/MS-based candidate reference measurement procedure for total gentamicin quantification to be used for standardization and harmonization of routine assays applied for therapeutic drug monitoring of this compound. Total gentamicin is the sum of the concentrations of five known congeners C1, C1a, C2, C2a and C2b.

52 Genetic Loci Influencing Myocardial Mass.

Background: Myocardial mass is a key determinant of cardiac muscle function and hypertrophy. Myocardial depolarization leading to cardiac muscle contraction is reflected by the amplitude and duration of the QRS complex on the electrocardiogram (ECG). Abnormal QRS amplitude or duration reflect changes in myocardial mass and conduction, and are associated with increased risk of heart failure and death.

The genetics of blood pressure regulation and its target organs from association studies in 342,415 individuals.

To dissect the genetic architecture of blood pressure and assess effects on target organ damage, we analyzed 128,272 SNPs from targeted and genome-wide arrays in 201,529 individuals of European ancestry, and genotypes from an additional 140,886 individuals were used for validation. We identified 66 blood pressure-associated loci, of which 17 were new; 15 harbored multiple distinct association signals. The 66 index SNPs were enriched for cis-regulatory elements, particularly in vascular endothelial cells, consistent with a primary role in blood pressure control through modulation of vascular tone across multiple tissues.

Ca(2+)/calmodulin-activated phosphodiesterase 1A is highly expressed in rabbit cardiac sinoatrial nodal cells and regulates pacemaker function.

Constitutive Ca(2+)/calmodulin (CaM)-activation of adenylyl cyclases (ACs) types 1 and 8 in sinoatrial nodal cells (SANC) generates cAMP within lipid-raft-rich microdomains to initiate cAMP-protein kinase A (PKA) signaling, that regulates basal state rhythmic action potential firing of these cells. Mounting evidence in other cell types points to a balance between Ca(2+)-activated counteracting enzymes, ACs and phosphodiesterases (PDEs) within these cells. We hypothesized that the expression and activity of Ca(2+)/CaM-activated PDE Type 1A is higher in SANC than in other cardiac cell types.

Gender specific profiles of white coat and masked hypertension impacts on arterial structure and function in the SardiNIA study.

Background: There is no definite consensus on the CV burden associated to Masked hypertension (MH) or White Coat Hypertension (WCH) — conditions that can be detected by out-of-office blood pressure measurements (24 hour Ambulatory Blood Pressure Monitoring, 24 h ABPM).

Methods: We investigated the association of WCH and MH with arterial aging, indexed by a range of parameters of large artery structure and function in 2962 subjects, taking no antihypertensive medications, who are participating in a large community-based population of both men and women over a broad age range (14–102 years).

Results: The overall prevalence of WCH was 9.