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Arrestins were discovered for their role in homologous desensitization of G-protein-coupled receptors (GPCRs). Later non-visual arrestins were shown to regulate several signaling pathways. Some of these pathways require arrestin binding to GPCRs, the regulation of others is receptor independent. Here, we demonstrate that arrestin-3 binds the E3 ubiquitin ligase parkin via multiple sites, preferentially interacting with its RING0 domain. Identification of the parkin domains involved suggests that arrestin-3 likely relieves parkin autoinhibition and/or stabilizes the enzymatically active "open" conformation of parkin. Arrestin-3 binding enhances ubiquitination by parkin of the mitochondrial protein mitofusin-1 and facilitates parkin-mediated mitophagy in HeLa cells. Furthermore, arrestin-3 and its mutant with enhanced parkin binding rescue mitofusin-1 ubiquitination and mitophagy in the presence of the Parkinson's disease-associated R275W parkin mutant, which is defective in both functions. Thus, modulation of parkin activity via arrestin-3 might be a novel strategy of anti-parkinsonian therapy., (© 2024 International Society for Neurochemistry.)

Objectives of this study were to measure both daily and periprandial plasma ghrelin concentrations of postpubertal Holstein heifers during prolonged undernutrition. Following an acclimation period, Holstein heifers [n = 10; 339.5 ± 8.6 kg of body weight (BW)] were fed ad libitum [well fed (WF); n = 5] or restricted to 50% of ad libitum intake [underfed (UF); n = 5) for 8 wk. Body condition scores (BCS) were recorded at the beginning and end of the treatment period, and weekly measurements of BW, plasma ghrelin, progesterone, and nonesterified fatty acids (NEFA) concentrations were obtained. Ovarian follicular and luteal structures were measured twice weekly via transrectal ultrasonography. Plasma ghrelin concentrations were also measured during a periprandial window bleed conducted at the end of the experiment. During the window bleed, samples were collected every 15 min between 0500 and 0900 h, with feed offered at 0700 h. Underfed heifers lost BW and BCS, whereas WF heifers gained weight and either increased or maintained BCS. Chronic underfeeding increased circulating ghrelin and NEFA concentrations. By wk 4 of the treatment period, circulating ghrelin concentrations of the UF heifers reached a plateau. Periprandial fluctuations in ghrelin concentrations were apparent as plasma ghrelin concentrations changed over time. Overall differences in periprandial plasma ghrelin concentrations were primarily due to prefeeding effects of plane of nutrition. Plasma ghrelin concentrations and change in BCS were negatively correlated such that heifers that lost the most BCS had the highest concentrations of circulating ghrelin. Two of the 5 UF heifers became anestrus by wk 3 of the treatment period. Despite being of similar age, the heifers that became anestrus had lower BW and plasma ghrelin concentrations than the UF heifers that continued to ovulate. In the current experiment, long-term undernutrition elicited ghrelin responses similar to those reported for shorter durations of nutrient restriction in cattle and other ruminants. These results demonstrate that plane of nutrition is a chronic regulator of plasma ghrelin concentrations, and that these concentrations can be experimentally manipulated in postpubertal heifers for up to 8 wk with no evidence of an adaptive response. [ABSTRACT FROM AUTHOR]

In major harbors and ports in the United States and its territories, the US Army Corps of Engineers maintains federal navigation channels in proximity to coral reefs (e.g., Honolulu Harbor, HI; Miami Harbor, FL; Apra Harbor, Guam) and other sensitive habitats. To effectively predict potential adverse impacts from dredging activities near these sensitive habitats, a holistic approach to improve understanding of the pressures on these habitats is needed to foster a more complete prediction of risk drivers. To achieve this, risk-based frameworks that account for the full range of natural and anthropogenic impacts need to be adapted and applied specifically for assessing and managing indirect dredging impacts on sensitive environments. In this article, we address this need by incorporating a drivers-pressures-stressors-condition-response (DPSCR 4 ) conceptual framework to broaden a comprehensive conceptual model of the coupled human-ecological system. To help understand these complex interactions, DPSCR 4 was applied to evaluate dredging and other unrelated environmental pressures (e.g., terrestrial runoff) in a proof-of-concept dredging project in Honolulu Harbor, Hawai'i, USA, with a focus on the indirect effects of dredge plumes. Particle tracking models and risk-based tools were used to evaluate sediment resuspended during a hypothetical mechanical dredging activity near sensitive coral habitats. Stoplight indicators were developed to predict indirect sediment plume impacts on coral and then compared to exposure modeling results. The strengths and limitations of the approach are presented and the incorporation of the risk framework into environmental management decisions is discussed. Integr Environ Assess Manag 2024;20:547-561. Published 2023. This article is a U.S. Government work and is in the public domain in the USA., (Published 2023. This article is a U.S. Government work and is in the public domain in the USA.)

The structural complexity of cold-water corals is threatened by ocean acidification. Increased porosity and thinning in structurally critical parts of the reef framework may lead to rapid physical collapse on an ecosystem scale, reducing their potential for biodiversity support. Understanding the structural-mechanical relationships of reef-forming corals is important to enable the use of in silico mechanical models as predictive tools that allow us to determine risk and timescales of reef collapse. Here, we analyze morphological variations of the branching architecture of the cold-water coral species Lophelia pertusa to advance mechanical in silico models based on their skeletal structure. We identified a critical size of five interbranch lengths that allows using homogenized finite element models to analyze mechanical competence. At smaller length scales, mechanical surrogate models need to explicitly account for the statistical morphological differences in the skeletal structure. We showed large morphological variations between fragments of L. pertusa colonies and branches, as well as dead and live skeletal fragments which are driven by growth and adaptation to environmental stressors, with no clear branching-specific patterns. Future in silico mechanical models should statistically model these variations to be used as monitoring tools for predicting risk of cold-water coral reefs crumbling. [ABSTRACT FROM AUTHOR]

G protein-coupled receptors (GPCRs) serve as critical communication hubs, translating a wide range of extracellular signals into intracellular responses that govern numerous physiological processes. In class-A GPCRs, conserved motifs mediate conformational changes of the active states of the receptor, and signal transduction is achieved by selectively binding to Ga proteins and/or adapter protein, arrestin. Apelin receptor (APJR) is a class-A GPCR that regulates a wide range of intracellular signalling cascades in response to apelin and elabela peptide ligands. Understanding how conserved motifs within APJR mediate activation and signal specificity remains unexplored. This study focuses on the functional roles of the DRY and NPxxY motifs within APJR by analyzing their impact on downstream signaling pathways across the receptor's conformational ensembles. Our findings provide compelling evidence that mutations within the conserved DRY and NPxxY motifs of APJR significantly alter its conformational preferences where modification of DRY motif leads to abrogation of G-protein coupling and mutation of NPxxY motif causing abolition of ß-arrestin-2 recruitment. These observations shed light on the importance of these motifs in APJR activation and its potential for functional selectivity, highlighting the role of DRY/NPxxY as conformational switches of APJR signalling. [ABSTRACT FROM AUTHOR]

G protein-coupled receptors (GPCRs) are the largest family of transmembrane receptors and primarily signal through two main effector proteins: G proteins and β-arrestins. Many agonists of GPCRs promote "biased" responses, in which different cellular signaling pathways are activated with varying efficacies. The mechanisms underlying biased signaling have not been fully elucidated, with many potential "hidden variables" that regulate this behavior. One contributor is "location bias," which refers to the generation of unique signaling cascades from a given GPCR depending upon the cellular location at which the receptor is signaling. Here, we review evidence that GPCRs are expressed at and traffic to various subcellular locations and discuss how location bias can impact the pharmacologic properties and characterization of GPCR agonists. We also evaluate how differences in subcellular environments can modulate GPCR signaling, highlight the physiological significance of subcellular GPCR signaling, and discuss the therapeutic potential of exploiting GPCR location bias., (© 2023 Wiley Periodicals LLC.)

Interfacial charge and strain distributions inside artificial perovskite ABO3 heterostructures often affect intriguing physical properties that are important to device performance. Normally, both charge and strain coexist across the interfaces, and their exact roles in determining the properties remain elusive. In the present work, La0.7Sr0.3MnO3 (LSMO) ultrathin films were grown on (001)-0.7Pb(Mg1/3Nb2/3)O3-0.3PbTiO3 (PMNPT) single-crystal substrates to discriminate between the effect of charge and strain on the transport and magnetoelectric properties. In heterostructures with thicker LSMO films, the strain effect dominates the resistance and the magnetic moment depends on the external electric field. With the decreasing LSMO thickness, the butterfly-like resistance–electric-field (R-E) and magnetization–electric-field (M-E) curves become loop-like, indicating that charge effects dominate strain effects in determining the electric field that controls the transport and magnetic properties. Furthermore, soft-x-ray absorption spectra of 32 and 4 nm LSMO/PMNPT samples at the Mn L edge under an applied electric field of ±6 kV/cm indicate that orbital reconstruction also plays an important role in interfacial magnetoelectric coupling. [ABSTRACT FROM AUTHOR]

Direct oral anticoagulants (DOACs) are increasingly being used due to their improved efficacy/safety ratio and lower clinical and economic burden when compared to vitamin K antagonists. However, bleeding is still the most frequent complication associated with DOACs, and although rare, bleeding episodes can be life-threatening or critical. The impact of DOAC anticoagulation activity during a bleeding event must be evaluated according to patient clinical assessment, dosage and time from last intake, the presence of comorbidities (especially kidney and liver dysfunction), and, whenever possible, coagulation tests. Unfortunately, DOACs' anticoagulation activity is not easily or usually detectable in routine common coagulation testing. Specific DOAC tests allow for specific drug monitoring, but they are too time consuming, and are usually unavailable in routine emergency practice. If a clinically relevant DOAC plasma concentration is assumed or proven in a severe bleeding scenario, DOAC reversal is needed to restore hemostasis. This experts' consensus provides a narrative review about DOAC reversal and practical life-threatening bleeding management in several scenarios (trauma, intracranial hemorrhage and gastrointestinal bleeding), focusing on the selection of patients to whom specific reversal agents should be given. [ABSTRACT FROM AUTHOR]

Nursing has a long history of advocacy aimed at improving patient care, enhancing healthcare systems, and influencing public policy. While substantial evidence exists on the role of nurses in advocating for individual patients, there is limited research on policy-level advocacy by nursing organizations. Existing literature often focuses on the role of advocacy groups in shaping policy but rarely explores the unique contributions of nursing organizations, particularly in areas such as biochemical considerations in health policy. Prior reviews have examined various aspects of policy advocacy, but a comprehensive evaluation of current research is needed to identify gaps and guide future studies. A scoping review was conducted to map existing literature on policy advocacy by nursing organizations. Searches across six databases identified both research studies and non-research articles. The review revealed a limited but expanding body of empirical research on policy advocacy by nursing organizations, which is primarily focused on national-level activities. Regional or state-level policy advocacy was largely overlooked. Many studies used historical, qualitative, or retrospective designs, which limits understanding of the long-term impacts of nursing advocacy on policy. Key barriers to nurses' engagement in policymaking included insufficient mentorship, inadequate training, time limitations, and low motivation. Overall, nurse participation in policy-making was reported as low to moderate. This review highlights the need for more rigorous empirical research on nursing organizations' policy advocacy. Further studies should focus on the impact of nurse-led policy advocacy at the regional level and explore the integration of nursing perspectives in shaping policies. In addition, future research could examine organizational decision-making processes, the influence of institutional culture, and the role of policymakers and stakeholders. By addressing these areas, nursing organizations can strengthen their role in shaping health policy and ensure that both community and scientific insights are integrated into healthcare systems. [ABSTRACT FROM AUTHOR]

Cabral, A.P. and Noernberg, M.A., 2024. Morphological characteristics of an open shelf ridge at Rio Grande do Norte continental shelf, NE Brazil. Journal of Coastal Research, 40(6), 1166–1181. Charlotte (North Carolina), ISSN 0749-0208. This paper describes for the first time the occurrence of an open shelf ridge (OSR) in the South Atlantic Ocean, evidencing morphological differences with respect to occurrences in other regions. The unique configuration of this OSR derives from the characteristics of the shallow continental shelf frontal to the Calcanhar Cape, Rio Grande do Norte State, Brazil, where it is located. It is a shallow, narrow, stepped shelf with an escarpment corresponding to a drowned shoreline around the 35 m isobath. There are extensive siliciclastic and carbonate sand deposits, sand ribbons, subaqueous dune fields, coral reefs, and calcareous algae patches. The high transparency of the water allows the use of multitemporal optical satellite images from remote sensors in the bathymetric modeling and morphodynamic description, in conjunction with echo sounder surveys, in situ sampling, and modeling. The metocean conditions of the region were determined from current and wind data obtained in situ, as well as data from the Hybrid Coordinate Ocean Model (HYCOM) and Regional Ocean Modeling System (ROMS) numerical models. Combining these data allowed the identification, characterization, and analysis of the metocean patterns over the OSR. Superimposed onto the OSR, there is a field of asymmetric subaqueous dunes transverse to the ridge axis with wavelengths between 150 m and 2 km and heights between 2.5 m and 9 m, with a tendency for sediment transport offshore northwestward of the OSR crest. The synergistic effect of the dominant NE winds and the North Brazil Current with tidal currents drives the main metocean forcings. The hydrodynamic pattern for the main sedimentary deposit areas is described, and the effect of the OSR on general subaqueous dune field configuration is presented. [ABSTRACT FROM AUTHOR]

It is broadly recognized that intramolecular electric fields, produced by the protein scaffold and acting on the active site, facilitate enzymatic catalysis. This field effect can be described by several theoretical models, each of which is intuitive to varying degrees. In this contribution, we show that a fundamental effect of electric fields is to generate electrostatic potentials that facilitate the energetic alignment of reactant frontier orbitals. We apply this model to demystify the impact of electric fields on high-valent iron-oxo heme proteins: catalases, peroxidases, and peroxygenases/monooxygenases. Specifically, we show that this model easily accounts for the observed field-induced changes to the spin distribution within peroxidase active sites and explains the transition between epoxidation and hydroxylation pathways seen in Cytochrome P450 active site models. Thus, for the intuitive interpretation of the chemical effect of the field, the strategy involves analyzing the response of the orbitals of active site fragments, and their energetic alignment. We note that the energy difference between fragment orbitals involved in charge redistribution acts as a measure for the chemical hardness/softness of the reactive complex. This measure, and its sensitivity to electric fields, offers a single parameter model from which to quantitatively assess the effects of electric fields on reactivity and selectivity. Thus, the model provides an additional perspective to describe electrostatic preorganization and offers ways for its manipulation. [ABSTRACT FROM AUTHOR]

The geochemical composition of sediment cores can serve as a proxy for reconstructing past human and nature-driven environmental and climatic changes. We investigated the temporal variation in the concentrations and fluxes of polycyclic aromatic compounds (PACs) which include polycyclic aromatic hydrocarbons (PAHs), oxygenated PAHs, and azaarenes in the Sihailongwan Maar Lake and found that they remained low before 1950. The PAC concentrations and fluxes increased substantially since 1950, which was in good agreement with the fast socio-economic development, industrialization, and associated growth in fossil fuel consumption in China, particularly since the 1980s. After 2010, the PAC fluxes decreased, which was consistent with the implementation of air pollution control policies in China at that time. The concentration ratios of the sums of low to high molecular weight PAHs (LMW-PAHs/HMW-PAHs), benzo[e]pyrene/benzo[a]pyrene, and benzo[a]anthracene-7,12-dione/benzo[a]anthracene all decreased from bottom to top of the sediment core, reflecting the rapidly increasing contribution of emissions derived from high-temperature fossil fuel combustion (energy, transport and industry) to the PAC emissions in recent times at the expense of biomass burning. In addition, these data reflect the increasing local sources of PACs in more recent times because of the enhanced human activities in the area surrounding the Maar lake. Our results demonstrate that PAC fluxes and concentrations in sediment cores reflect the regional and national economic development and the efficiency of pollution control measures. [ABSTRACT FROM AUTHOR]

Approximately 75% of the world's and California's shores are rocky. Rocky shores are of biological interest owing to their diverse and productive species assemblages, where waves and currents play a critical role in larval dispersal and recruitment. Surface variability for nearshore (5⪅depth⪅60m) $(5\lessapprox \mathrm{d}\mathrm{e}\mathrm{p}\mathrm{t}\mathrm{h}\lessapprox 60\hspace*{.5em}\mathrm{m})$ rocky bottoms at intermediate wave scale 1/750

Purpose: The purpose of the study was to determine the effect of moderately strenuous aerobic exercise training on heart rate variability (HRV) and heart rate turbulence (HRT) in patients with an implantable cardioverter defibrillator (ICD). Methods: Patients were randomized to a 24-week home-based aerobic exercise (EX) training program (n = 84) or to usual care (UC) (n = 76). All subjects underwent 24-h Holter monitoring at baseline, 8 and 24 weeks. Generalized estimating equations were used to test the effects of exercise on HRV and HRT outcomes. Results: The study group was comprised of n = 160 patients (124 M, 36 F, age 54.9 ± 12.2 years) with an ICD for primary (43%) or secondary prevention (57%). Compared to UC, EX was associated with a significant improvement in parasympathetic HRV for root mean square of successive differences (rMSSD; p =.05) at 8 weeks and global HRV for standard deviation of all normal (N-N) intervals (SDNN; p =.05) and standard deviation of 5-min averages N-N intervals (SDANN; p =.03) at 24 weeks. When stratified by adherence, those who were ≥80% adherent (minutes/week) had significant improvements in parasympathetic HRV (rMSSD, pNN50) and global HRV (SDNN, SDANN) at 8 weeks, and a further significant improvement in global HRV (SDNN, SDANN, SDNN index) at 24 weeks. Neither HRT nor ventricular ectopy changed with exercise training. Conclusion: Moderately strenuous aerobic exercise improved parasympathetic and global HRV indices following an ICD, with greater adherence associated with greater improvements. Clinical trial registration: Clinicaltrials.gov: NCT 00522340. [ABSTRACT FROM AUTHOR]

Feline respiratory disease complex (FRDC) is a highly prevalent syndrome in cats that often result in fatal outcomes. FRDC etiology is complex, and often, multiple viral and bacterial pathogens are simultaneously associated with disease causation. There is limited information about the role of co-infections in pathogenesis and the current prevalence of pathogens in North America. We aimed to conduct a study using technical advances in molecular diagnosis and statistical modeling analysis to elucidate the occurrence of pathogens and how co-infections affect disease severity. We attained information from three diagnostic laboratories in North America regarding the occurrence of Bordetella bronchiseptica, Chlamydia felis, Mycoplasma, Felid alphaherpesvirus 1 (FeHV-1), feline calicivirus (FCV), and influenza A, along with age, seasonality, sex, and clinical signs. We also evaluated the role of co-infections in disease severity. These pathogens were also investigated in clinically normal cats (control). The most detected pathogens were Mycoplasma, FCV, and FeHV-1. Most pathogens were detected in the control group, highlighting the challenge of interpreting positive testing results. Co-infections of Mycoplasma and FCV, as well as Mycoplasma and FeHV-1, were important predictors of disease severity. Age, sex, and season had a minor impact on pathogen occurrence. This study provides new insights into FRDC and underlines the relevance of diagnostic panels to screen for a range of pathogens, providing knowledge for timely diagnosis and therapeutic interventions. [ABSTRACT FROM AUTHOR]

Background. Despite the guideline recommendation, implementation of the Cox‐maze (CM) IV procedure has been variable and current data are limited. Methods. We reviewed patients with concomitant CM IV procedure (05/2019−05/2020). The primary endpoints of the study were the success rate of surgical ablation and continuity of sinus rhythm (SR) 1 year after surgery. Secondary endpoints included permanent pacemaker (PPM) implantation, postoperative mortality, and identification of predictors for postoperative SR. Results. The concomitant CM IV procedure was performed in 92 patients. Indications were persistent atrial fibrillation (AF) in 40 patients (43.5%), paroxysmal AF in 36 (39.1%), and long‐standing persistent AF in 16 (17.4%). At hospital discharge, SR was achieved in 49 patients (63.6%) and PPM implantation was necessary in 12 patients (13%). At 1 year after surgical ablation, SR was seen in 31 patients (59.6%) and PPM implantation was required in six further patients (6.5%). Patients with long‐standing persistent AF were significantly less likely to achieve SR (odds ratio (OR): 0.18, p = 0.003), and postoperative mortality was significantly increased in this subgroup (hazard ratio (HR): 5.4, p = 0.02). In patients with enlarged left atrial (LA) diameter, the probability of achieving SR was significantly decreased (OR: 0.48, p = 0.045). Need for postoperative dialysis (HR: 12.9, p = 0.02) and prolonged stay in the intensive care unit (HR: 2.2, p = 0.01) were independently associated with increased mortality after CM IV. Conclusions. The cryothermal CM IV procedure has an overall 1‐year success rate of 60% with increased rates of PPM implantation. Patients with long‐standing persistent AF and increased LA diameter were significantly less likely to achieve SR. [ABSTRACT FROM AUTHOR]

Anthropogenic activities increase the level of dissolved heavy metals in some tropical near‐shore environments threatening reef ecosystems. The skeleton of stony corals like Porites species potentially provides a high‐resolution geochemical archive for past heavy metal concentrations, with potentially century long records revealing baseline values before large‐scale human disturbance. However, few data exist for heavy metal partitioning into coral skeleton aragonite. To address this, culturing experiments exposing Porites lobata and Porites lichen to a mixture of dissolved Cr, Mn, Ni, Cu, Zn, Ag, Cd, Sn, Hg, and Pb over a wide concentration range have been performed. Water samples were taken frequently to monitor changes in the heavy metal concentration. Laser ablation ICP‐MS measurements of the coral aragonite revealed metal concentrations that were positively correlated with Cr, Mn, Ni, Zn, Ag, Cd, and Pb concentrations in seawater. The DTE values for most metals appear dependent on the seawater metal content, approximating a power law, and therefore stabilize at higher seawater metal/Ca ratios. The partitioning of Pb into the coral skeleton is a notable exception, with DPb being stable around 2 to 1 across a large range of "natural" to highly polluted seawater Pb concentrations. This and the general agreement with partition coefficients estimated by previous work suggests that the reconstruction of the heavy metal concentration in seawater for ecosystem monitoring is possible. However, the high variability within and between coral colonies requires further study and suggests that multiple records from multiple coral colonies should be combined to obtain robust reconstructions. Key Points: Porites corals grow normally with increased exposure to multiple metals over >1 yearSkeletal partitioning variable within and between colonies and with seawater metal contentGood agreement with previous work, especially for Pb across a large range of metal content [ABSTRACT FROM AUTHOR]

The East Pisco Basin, occupying the coastal plain of Peru between 13°S and 16°S, is widely known for its extensive Eocene to Quaternary biosiliceous deposits and excellent preservation of fossil marine vertebrates. Biochronologic studies published over the past 35 years record a hiatus of about 13 million years (*32-19 Ma) separating the youngest Paleogene deposits (Otuma Formation) from the oldest Neogene deposits (Chilcatay Formation). We describe a newly identified Lower Miocene depositional sequence that lies below documented Chilcatay strata, rich in diatoms and benthic foraminifers, which we name the Tunga Formation. A low-latitude diatom assemblage from the Tunga Formation indicates an age of 21.6 to 20.5 Ma age, whereas an ash within basal Tunga strata yields an 206Pb/238U weighted mean age of 20.58 ± 0.13 Ma. Benthic foraminifer paleodepth analysis and the diatom assemblage of the Tunga Formation indicate deposition took place along the continental margin at upper bathyal depths under hypoxic conditions beneath highly productive waters, a scenario also supported by the presence of abundant clupeoid fish scales and dolomitized horizons. The Tunga Formation is characterized by a profound scarcity of cetacean fossils, unlike the cetacean-rich neritic sediments of the overlying Chilcatay Formation. [ABSTRACT FROM AUTHOR]

Chandarpur–Raipur sequence in Chattisgarh basin is represented as siliciclastic-dominated Chandarpur Group and carbonate-dominated Raipur Group. Here, we introduce 'Devsagar Sandstone Member', the only sandstone-dominated member in the carbonate-dominated Charmuria Formation of Raipur Group, that marks a period of rapid siliciclastic deposition identifying a phase of forced regression between two carbonate platforms of Charmuria–Chandi formations, thereby indicating a drastic change in palaeogeography of Raipur Group. In addition, this study revised the litho-stratigraphy of Mesoproterozoic Chattisgarh basin to clarify the confusion raised due to the existence of different stratigraphy in different basinal parts and different nomenclature for the same lithologic units. Detailed geological mapping with facies analysis in the eastern part of the basin manifests the entire basin-fill succession as part of the Chattisgarh basin itself, rather than sub-dividing some parts as Baradwar sub-basin and Singhora proto-basin. Singhora Group deposited in Singhora proto-basin has already been presented as equivalent of Chandarpur Group. Here we propose, Bamandihi–Saradih–Raigarh formations of Raipur Group in Baradwar sub-basin, as lateral equivalent of Gunderdehi–Chandi–Tarenga formations of Raipur Group and Sarnadih–Nandeli formations of Kharsiya Group in Chattisgarh basin. Inferred depositional environment and tectonic setting of Chattisgarh basin support the lithostratigraphic revision, which will help in basin analysis as well as intrabasinal–interbasinal correlation in regional and global contexts. Research highlights: Devsagar Sandstone Member introduced as the only sandstone-dominated member in carbonate-dominated Charmuria Formation of Raipur Group. Devsagar Sandstone Member represents a tidal shelf in between two carbonate ramp platforms (Charmuria and Chandi), marking a period of rapid siliciclastic deposition and the only phase of forced regression in overall sea-level rising scenario of the carbonate-dominated Raipur Group. Stratigraphy of Chattisgarh basin revised. The entire Chattisgarh succession is represented as deposits of Chattisgarh basin only, without further subdivision into sub-basin and/or proto-basin, thus resolving the stratigraphic and basinal correlation problem. [ABSTRACT FROM AUTHOR]

Arrestins were first discovered as proteins that selectively bind active phosphorylated GPCRs and suppress (arrest) their G protein-mediated signaling. Nonvisual arrestins are also recognized as signaling proteins regulating a variety of cellular pathways. Arrestins are highly flexible; they can assume many different conformations. In their receptor-bound conformation, arrestins have higher affinity for a subset of binding partners. This explains how receptor activation regulates certain branches of arrestin-dependent signaling via arrestin recruitment to GPCRs. However, free arrestins are also active molecular entities that regulate other signaling pathways and localize signaling proteins to particular subcellular compartments. Recent findings suggest that the two visuals, arrestin-1 and arrestin-4, which are expressed in photoreceptor cells, not only regulate signaling via binding to photopigments but also interact with several nonreceptor partners, critically affecting the health and survival of photoreceptor cells. Detailed in this overview are GPCR-dependent and independent modes of arrestin-mediated regulation of cellular signaling. © 2023 Wiley Periodicals LLC., (© 2023 Wiley Periodicals LLC.)

Cardiac arrhythmias are among the leading causes of morbidity and mortality worldwide. While antiarrhythmic drugs traditionally represent the first-line management strategy, their use is often limited by profound proarrhythmic effects. Several studies, including randomized control trials (RCTs), have demonstrated the antiarrhythmic efficacy of ranolazine, which is registered as an antianginal agent, while also establishing its safety profile. This review compiles clinical evidence investigating the antiarrhythmic properties of ranolazine, focusing primarily on ventricular tachycardia (VT) and atrial fibrillation (AF), as they are common rhythm abnormalities with serious complications. Data from RCTs indicate that ranolazine reduces VT incidence, although this effect is not universal. Therefore, we attempt to better describe the patient population that gains the most benefit from ranolazine due to VT suppression. Additionally, ranolazine is known to enhance the conversion rate of AF to sinus rhythm when combined with other antiarrhythmic drugs such as amiodarone, highlighting its synergistic effect in the atrium without provoking ventricular dysrhythmias. Despite the heterogeneity in the currently available data, ranolazine appears to be an effective and safe option for the management of various arrhythmias. [ABSTRACT FROM AUTHOR]