ATPase Research Articles

Progressive central cardiorespiratory rate downregulation and intensifying epilepsy lead to sudden unexpected death in epilepsy in mouse model of the most common human ATP1A3 mutation.

This study was undertaken to test the following hypotheses in the Atp1a3Mashl/+ mouse (which carries the most common human ATP1A3 (the major subunit of the neuronal Na+/K+-adenosine triphosphatase [ATPase]) mutation, D801N): sudden unexpected death in epilepsy (SUDEP) occurs during seizures and is due to terminal apneas in some and due to lethal cardiac arrhythmias in others; and Atp1a3Mashl/+ mice have central cardiorespiratory dysregulation and abnormal respiratory drive. Comparison was made of littermate wild-type and Atp1a3Mashl/+ groups using (1) simultaneous invivo video-telemetry recordings of electroencephalogram, electrocardiogram, and breathing; (2) whole-body plethysmography; and (3) hypoglossal nerve recordings. In Atp1a3Mashl/+ mice, (1) SUDEP consistently occurred during seizures that were more severe than preterminal seizures; (2) seizure clustering occurred in periods preceding SUDEP; (3) slowing of breathing rate (BR) and heart rate was observed preictally before preterminal and terminal seizures; and (4) the sequence during terminal seizures was as follows: bradypnea with bradycardia/cardiac arrhythmias, then terminal apnea, followed by terminal cardiac arrhythmias. Compared to wild-type, mutants showed (1) abnormal resting BR variability but no difference in cardiac PR, QRS, QTc, or RR intervals; (2) abnormal hypoglossal nerve firing in response to hypoxia; and (3) abnormal whole-body plethysmography, consisting of baseline predisposition to apnea and abnormal responses to respiratory challenge. Atp1a3Mashl/+, an alternating hemiplegia of childhood (AHC) model, is also a revealing SUDEP model of Na+/K+-ATPase mutation resulting in abnormal central respiratory drive and in progressive cardiorespiratory dysregulation concurrent with worsening epilepsy. SUDEP results from seizure-triggered bradypnea/bradycardia followed by terminal apnea, then terminal cardiac arrhythmias. Because many epilepsy/SUDEP models of other etiologies manifest secondary ATPase deficiency, future studies in those models may benefit from considering possible contributions of ATPase dysfunction to SUDEP in those models too.

RapA opens the RNA polymerase clamp to disrupt post-termination complexes and prevent cytotoxic R-loop formation.

Following transcript release during intrinsic termination, Escherichia coli RNA polymerase (RNAP) often remains associated with DNA in a post-termination complex (PTC). RNAPs in PTCs are removed from the DNA by the SWI2/SNF2 adenosine triphosphatase (ATPase) RapA. Here we determined PTC structures on negatively supercoiled DNA and with RapA engaged to dislodge the PTC. We found that core RNAP in the PTC can unwind DNA and initiate RNA synthesis but is prone to producing R-loops. Nucleotide binding to RapA triggers a conformational change that opens the RNAP clamp, allowing DNA in the RNAP cleft to reanneal and dissociate. We show that RapA helps to control cytotoxic R-loop formation in vivo, likely by disrupting PTCs. We suggest that analogous ATPases acting on PTCs to suppress transcriptional noise and R-loop formation may be widespread. These results hold importance for the bacterial transcription cycle and highlight a role for RapA in maintaining genome stability.

Genetic variation features of neonatal hyperbilirubinemia caused by inherited diseases.

Genetic factors play an important role in neonatal hyperbilirubinemia (NH) caused by genetic diseases. To explore the characteristics of genetic mutations associated with NH and analyze the correlation with genetic diseases. This was a retrospective cohort study. One hundred and five newborn patients diagnosed with NH caused by genetic diseases were enrolled in this study between September 2020 and June 2023 at the Second Affiliated Hospital of Xiamen Medical College. A 24-gene panel was used for gene sequencing to analyze gene mutations in patients. The data were analyzed via Statistical Package for the Social Sciences 20.0 software. Seventeen frequently mutated genes were found in the 105 patients. Uridine 5'-diphospho-glucuronosyltransferase 1A1 (UGT1A1) variants were identified among the 68 cases of neonatal Gilbert syndrome. In patients with sodium taurocholate cotransporting polypeptide deficiency, the primary mutation identified was Na+/taurocholate cotransporting polypeptide Ntcp (SLC10A1). Adenosine triphosphatase 7B (ATP7B) mutations primarily occur in patients with hepatolenticular degeneration (Wilson's disease). In addition, we found that UGT1A1 and glucose-6-phosphate dehydrogenase mutations were more common in the high-risk group than in the low-risk group, whereas mutations in SLC10A1, ATP7B, and heterozygous 851del4 mutation were more common in the low-risk group. Genetic mutations are associated with NH and significantly increase the risk of disease in affected newborns.

Structural Insight on the Selectivity of Calyx[4]Arene-Based Inhibitors of Mg2+-Dependent Atp-Hydrolases.

Located in plasma membranes, ATP hydrolases are involved in several dynamic transport processes, helping to control the movement of ions across cell membranes. ATP hydrolase acts as a transport protein, converting energy from ATP hydrolysis into transport molecules against their concentration gradients. In addition to energy metabolism and active transport, ATP hydrolase is essential for maintaining cellular homeostasis and cell function. This study focused on the domain architecture model of P-type ATPases, which participate in the reaction cycles of ATP hydrolysis carried out by membrane transport systems - Na+, K+-ATPase and Ca2+, Mg2+-ATPase. Targeted modulation of Na+, K+-ATPase and Ca2+, Mg2+-ATPase by unnatural drugs is of greatest interest due to the lack of known effectors. This new discovery presents a convenient model based on our recent experimental studies of the membrane structures and myocytes of the uterine smooth muscle, the myometrium. This current study strongly supports the fact that nanosized calix[4]arenes functionalised on the upper rings of the macrocycle with biologically active phosphonic acid fragments can serve as selective and potent inhibitors of cation-transporting electroenzymes. This is how we discovered that calix[4]arene of methylenebisphosphonic acid C-97 and calix[4]arene of bis-aminophosphonic acid C-107 selectively and effectively (I0.5 <100 nM) inhibit the activity of Mg2+, ATP-dependent electrogenic Na+ K+ plasma membrane pump. As drug discovery in the field of Mg2+-ATPase inhibitors is uncharted territory, basic research holds the key to explaining and predicting the mechanism of interaction and action of different classes of compounds. In light of the presented results, new calix[4]arene compounds can be used as potent inhibitors of Mg2+, ATP-dependent electrogenic ion pumps.

KRBP72 facilitates ATPase-dependent editing progression through a structural roadblock in mitochondrial A6 mRNA.

Uridine insertion/deletion editing of mitochondrial messenger RNAs (mRNAs) in kinetoplastids entails the coordinated action of three complexes. RNA Editing Catalytic Complexes (RECCs) catalyze the enzymatic reactions, while the RNA Editing Substrate Binding Complex (RESC) and RNA Editing Helicase 2 Complex (REH2C) coordinate interactions between RECCs, mRNAs and hundreds of guide RNAs that direct edited sequences. Additionally, numerous auxiliary factors are required for productive editing of specific mRNAs. Here, we elucidate the role of KRBP72, an editing auxiliary factor of the ABC adenosine triphosphatase (ATPase) family that exhibits RNA-binding activity. In procyclic form Trypanosoma brucei, KRBP72 knockdown leads to a pause in editing at the base of a predicted stem loop structure in adenosine triphosphate synthase subunit 6 (A6) mRNA. Enhanced cross-linking and affinity purification revealed KRBP72 binding sites both within and upstream of this stem loop. KRBP72 ATPase activity is essential for its A6 mRNA editing function; however, its RNA-binding activity is dispensable. KRBP72 interacts with most RESC proteins in an RNase-sensitive manner. By contrast, RESC12A associates with KRBP72 in an RNase-insensitive fashion, and RESC12A promotes KRBP72's interaction with RNA. Hence, KRBP72 ATPase activity facilitates progression of editing through a challenging secondary structure, highlighting this protein's crucial role in A6 mRNA editing.

Adenosine signaling in tumor-associated macrophages and targeting adenosine signaling for cancer therapy.

This review examined the critical role of adenosine signaling in modulating the behavior of tumor-associated macrophages (TAMs), a key determinant of the tumor microenvironment (TME). Adenosine is an immunosuppressive metabolite that is highly enriched in the TME due to elevated expression of adenosine triphosphatase (ATPase). Adenosine influences polarization of TAMs through A2A and A2B receptors, which drives a phenotype that supports tumor progression and immune evasion. The adenosine-mediated regulation of TAMs significantly suppresses the TME, dampening the efficacy of current immunotherapies. Targeting the adenosine pathway has shown potential in preclinical studies through reversal of the immunosuppressive microenvironment and antitumor immune response enhancement. Clinical trials are currently underway to determine the impact of A2A receptor antagonists, and CD39 and CD73 inhibition, enzymes that are pivotal in adenosine production, in various cancers. The current understanding of the CD39-CD73-adenosine axis in TAM regulation and the emerging strategies targeting adenosine signaling pathway for therapeutic intervention are the subjects of this review. The current clinical trials focusing on adenosine pathway inhibitors in combination with existing therapies to improve clinical outcomes are summarized and the need for continued research to refine these approaches for cancer treatment is emphasized.

ATP6V1C1, associated with the tumor microenvironment and mTORC1 signaling pathway, is a potential diagnostic, prognostic, and therapeutic biomarker for hepatocellular carcinoma

BackgroundHepatocellular carcinoma (HCC) is a global health challenge with high mortality. ATP6V1C1, one of the subunit genes of vacuolar adenosine triphosphatase (V-ATPase), is a potential oncogene. However, its role in HCC remains unclear.Materials and methodsDifferential analysis of mRNA and microRNA (miRNA), combined with machine learning, identified ATP6V1C1 as a potential biomarker for HCC. The expression and prognostic role of ATP6V1C1 in HCC were evaluated. Additionally, we explored the distribution of ATP6V1C1 in HCC tumor microenvironment (TME) at single-cell and spatial transcriptome levels. Furthermore, the association between ATP6V1C1 and malignant biological features, TME characteristics, and therapy response in HCC was investigated. Finally, in vitro experiments validated the effects of ATP6V1C1 on the malignant phenotype of HCC.ResultsATP6V1C1 had higher expression in HCC tissues compared to paired normal tissues. Upregulated ATP6V1C1 was associated with poor HCC prognosis. ATP6V1C1 was primarily expressed in malignant cells and the tumor region in HCC TME. A positive correlation was observed between ATP6V1C1 expression and the activation of cancer-related pathways. The high ATP6V1C1 expression group exhibited increased pro-tumorigenic immune infiltration, inhibited anti-tumor immune activity, and high tumor proliferation rate. HCC patients of low ATP6V1C1 expression group had more clinical response to anti-tumor therapies. Knockdown of ATP6V1C1 impaired the proliferation, migration, and invasion of HCC cells by downregulating the mTORC1 signaling pathway.ConclusionATP6V1C1 multifacetedly contributes to the oncogenesis and progression of HCC and is a promising diagnostic and prognostic biomarker with predictive value on therapy response.

Guanidine-Derived Polymeric Nanoinhibitors Target the Lysosomal V-ATPase and Activate AMPK Pathway to Ameliorate Liver Lipid Accumulation.

Current research efforts in polymer and nanotechnology applications are primarily focused on cargo delivery to enhance the therapeutic index, with limited attention being paid to self-molecularly targeted nanoparticles, which may also exhibit significant therapeutic potential. Long-term and anomalous lipid accumulation in the liver is a highly relevant factor contributing to liver diseases. However, the development of the reliable medications and their pharmacological mechanisms remain insufficient. Herein, a polyguanide nanoinhibitors (PGNI) depot is constructed by copolymerizing biguanide derivatives in different proportions onto prepolymers. The nanoinhibitors for their ability to ameliorate lipid accumulation in vitro and in vivo is screened, and subsequently demonstrated that covalently polymeric guanidine chains exhibit superior efficacy in ameliorating hepatic lipid accumulation via heterogeneous mechanisms compared to small-molecule guanidine. It is found that PGNIs stabilize guanidine metabolism in the liver, preferably for biosafety. More importantly, PGNI is ingested and localized in hepatocyte lysosomes and is locked to interact with vesicular adenosine triphosphatase (V-ATPase) on lysosomes, leading to the inhibition of V-ATPase and lysosomal acidification, thereby activating the AMPK pathway, reducing fatty acid synthesis, and enhancing lipolysis and fatty acid oxidation. These results imply that polymer-formed nanoparticles can serve as targeted inhibitors, offering a novel approach for therapeutic applications.

Ubiquitin regulatory X (UBX) domain-containing protein 6 is essential for autophagy induction and inflammation control in macrophages

Ubiquitin regulatory X (UBX) domain-containing protein 6 (UBXN6) is an essential cofactor for the activity of the valosin-containing protein p97, an adenosine triphosphatase associated with diverse cellular activities. Nonetheless, its role in cells of the innate immune system remains largely unexplored. In this study, we report that UBXN6 is upregulated in humans with sepsis and may serve as a pivotal regulator of inflammatory responses via the activation of autophagy. Notably, the upregulation of UBXN6 in sepsis patients was negatively correlated with inflammatory gene profiles but positively correlated with the expression of Forkhead box O3, an autophagy-driving transcription factor. Compared with those of control mice, the macrophages of mice subjected to myeloid cell-specific UBXN6 depletion exhibited exacerbated inflammation, increased mitochondrial oxidative stress, and greater impairment of autophagy and endoplasmic reticulum-associated degradation pathways. UBXN6-deficient macrophages also exhibited immunometabolic remodeling, characterized by a shift to aerobic glycolysis and elevated levels of branched-chain amino acids. These metabolic shifts amplify mammalian target of rapamycin pathway signaling, in turn reducing the nuclear translocation of the transcription factor EB and impairing lysosomal biogenesis. Together, these data reveal that UBXN6 serves as an activator of autophagy and regulates inflammation to maintain immune system suppression during human sepsis.

Spontaneous spreading depolarizations originate subcortically in a novel mouse model of familial hemiplegic migraine type 2

The mechanisms of initiation of spreading depolarization (SD) are understudied due to a paucity of disease models with spontaneously occurring events. We here present a novel mouse model of familial hemiplegic migraine type 2 (FHM2), expressing the missense T345A-mutated α2 subunit of the Na+/K+ adenosine triphosphatase pump (Atp1a2T345A). Homozygous Atp1a2T345A mice showed regular spontaneous SDs that exhibit a diurnal rhythm and typically originate from the hippocampus. Heterozygous Atp1a2T345A mice rarely exhibited spontaneous SDs and, for electrically induced SDs, only showed an increased propagation speed, whereas homozygotes showed both increased propagation and decreased threshold. Remarkably, despite hippocampal hyperexcitability, spontaneous SDs in Atp1a2T345A mice were only rarely associated with epileptic behavior, and seizure expression during kindling was decreased. Spontaneous SDs could be prevented by modulation of persistent sodium currents. Hippocampal SDs occurred in the presence of an NMDA-receptor antagonist, but these events did not reach the cortex, suggesting that initiation and propagation of SD depend on different mechanisms in this model.

Mechanism of polyadenylation-independent RNA polymerase II termination.

The mechanisms underlying the initiation and elongation of RNA polymerase II (Pol II) transcription are well-studied, whereas termination remains poorly understood. Here we analyze the mechanism of polyadenylation-independent Pol II termination mediated by the yeast Sen1 helicase. Cryo-electron microscopy structures of two pretermination intermediates show that Sen1 binds to Pol II and uses its adenosine triphosphatase activity to pull on exiting RNA in the 5' direction. This is predicted to push Pol II forward, induce an unstable hypertranslocated state and destabilize the transcription bubble, thereby facilitating termination. This mechanism of transcription termination may be widely used because it is conceptually conserved in the bacterial transcription system.

Prospective study on immune function in renal transplant patients during perioperative period: A prospective cohort study.

Delayed graft function (DGF) is a type of acute renal failure that is closely linked to the immune system. The objective of this study is to investigate immune trends during the perioperative period of renal transplantation and compare the variations between patients with DGF and immediate graft function (IGF). A total of 48 kidney transplant patients were enrolled. Parameters including stimulated adenosine triphosphatase concentrations (sATP), nonstimulated ATP concentrations, white blood cells, and lymphocyte count were assessed. Patients were categorized into the DGF or IGF group. Clinical information and changes in immune markers were compared. Receiver operating characteristic analysis was performed to determine the sensitivity and specificity in predicting DGF. Additionally, separate immune function analyses were conducted for the 3 infection cases. Following induction immunosuppressive therapy, white blood cells, and neutrophil count showed a significant initial increase followed by a gradual decline. Lymphocyte count, nonstimulated ATP concentrations, and sATP exhibited an initial significant decrease followed by a slow recovery. Immune markers between the DGF and IGF groups were significantly different at day 4 after renal transplantation. Only sATP levels at day 4 after renal transplantation (area under the curve = 0.731, sensitivity = 0.864, specificity = 0.684) demonstrated predictive value for DGF occurrence. Among the 3 infection cases, 2 cases exhibited persistently decreased sATP levels and died within the first month and 6 months, while the remaining case showed a recovery of sATP levels at D9 and survived. These findings indicate that sATP level can potentially serve as a biomarker reflecting the impact of immunosuppressants. Poor recovery of sATP may be associated with DGF, infection, or even mortality.

Dephosphorylation and ion binding in prokaryotic calcium transport

Calcium (Ca 2+ ) signaling is fundamental to cellular processes in both eukaryotic and prokaryotic organisms. While the mechanisms underlying eukaryotic Ca 2+ transport are well documented, an understanding of prokaryotic transport remains nascent. LMCA1, a Ca 2+ adenosine triphosphatase (ATPase) from Listeria monocytogenes , has emerged as a prototype for elucidating structure and dynamics in prokaryotic Ca 2+ transport. Here, we used a multidisciplinary approach integrating kinetics, structure, and dynamics to unravel the intricacies of LMCA1 function. A cryo–electron microscopy (cryo-EM) structure of a Ca 2+ -bound E1 state showed ion coordination by Asp 720 , Asn 716 , and Glu 292 . Time-resolved x-ray solution scattering experiments identified phosphorylation as the rate-determining step. A cryo-EM E2P state structure exhibited remarkable similarities to a SERCA1a E2-P* state, which highlights the essential role of the unique P-A domain interface in enhancing dephosphorylation rates and reconciles earlier proposed mechanisms. Our study underscores the distinctiveness between eukaryotic and prokaryotic Ca 2+ ATPase transport systems and positions LMCA1 as a promising drug target for developing antimicrobial strategies.

The Protective Effect of the Supplementation with an Extract from Aronia melanocarpa L. Berries against Cadmium-Induced Changes of Chosen Biomarkers of Neurotoxicity in the Brain-A Study in a Rat Model of Current Lifetime Human Exposure to This Toxic Heavy Metal.

Since even low-level environmental exposure to cadmium (Cd) can lead to numerous unfavourable health outcomes, including damage to the nervous system, it is important to recognize the risk of health damage by this xenobiotic, the mechanisms of its toxic influence, and to find an effective protective strategy. This study aimed to evaluate, in a female Wistar rat model of current human environmental exposure to Cd (1 and 5 mg/kg of diet for 3-24 months), if the low-to-moderate treatment with this element can harm the brain and whether the supplementation with a 0.1% Aronia melanocarpa L. (Michx.) Elliott berries (chokeberries) extract (AE) can protect against this effect. The exposure to Cd modified the values of various biomarkers of neurotoxicity, including enzymes (acetylcholinesterase (AChE), sodium-potassium adenosine triphosphatase (Na+/K+-ATPase), phospholipase A2 (PLA2), and nitric oxide synthase 1 (NOS1)) and non-enzymatic proteins (calmodulin (CAM), nuclear factor erythroid 2-related factor 2 (Nrf2), and Kelch-like ECH-associated protein 1 (KEAP1)) crucial for the functioning of the nervous system, as well as the concentrations of calcium (Ca) and magnesium (Mg) and some metalloproteinases (MMPs) and their tissue inhibitors (TIMPs) in the brain tissue. The co-administration of AE, partially or entirely, protected from most of the Cd-induced changes alleviating its neurotoxic influence. In conclusion, even low-level chronic exposure to Cd may adversely affect the nervous system, whereas the supplementation with A. melanocarpa berries products during the treatment seems a protective strategy.

Hepatoprotective Activity of Gingko biloba‐Mediated TiO2 NPs Against Acetaminophen‐Induced Albino Rats‐ In Vitro Studies

AbstractNumerous effects of “titanium dioxide nanoparticles (TiO2 NPs)” have been described and significantly utilized in complementary drugs for many decades. This study is conducted to analyze the therapeutic efficiency of TiO2 NPs against the acetaminophen‐(AMP) induced toxicity. TiO2 NPs were initially prepared using Ginkgo biloba leaf extract as reducing and stabilizing agent. The prepared TiO2 NPs were studied using various spectroscopic and microscopic techniques. AFM, TEM, XRD, and DLS studies have confirmed the formation of TiO2 NPs with size between 20 to 60 nm with negative surface charge of about −12 mV. Later, hepatoprotective studies were performed by administering AMP to albino mice only once at a dosage of 2 g/kg p.o. Post 24 h of AMP intoxication, the animals were treated orally with three different doses of TiO2 NPs (150, 100, and 50 mg/kg) or silymarin at an amount of 50 mg/kg p.o., administered only once. Post 24 h of last treatment, all the animals were surrendered to death. The group of mice administered with AMP displayed a substantial raise in the serum alkaline phosphatase (560 ± 31.90), lactate dehydrogenase (167 ± 10.17), aspartate amino transferase (251 ± 14.82), alanine amino transferase (326 + 18.96), bilirubin (2.2 ± 1.066), cholesterol (96.7 ± 6.2), and albumin (6.0 ± 1.27) in serum, which signified the liver damage. A considerably depleted level of glutathione (5.4 + 1.24) was detected in the mice intoxicated with AMP. The activities of catalase (33.2 ± 2.66) and superoxide dismutase (36 ± 2.93) declined after exposure to acetaminophen, resulting in oxidative stress in liver. The performance of adenosine triphosphatase (901 ± 50.7) and glucose‐6‐phosphatase (3.9 + 1.15) were considerably inhibited after administrating with AMP. On treating with TiO2 NPs, all the variables reversed significantly towards regular levels and were noticed to be nontoxic. The groups treated with TiO2 NPs exhibited less activity of ALT, AST, LDH, and SALP in serum, indicating the protective effect of TiO2 NPs to prevent liver damage. Exposure with TiO2 NPs inverted the cholesterol, albumin, and bilirubin levels towards normal, which is similar to silymarin treatment. TiO2 NPs exhibited a substantial change in tissue and blood biochemical parameters with that of control groups. These results indicate that TiO2 NPs possesses hepatoprotective properties that mitigate the hepatotoxicity induced by acetaminophen in rats. Hence, TiO2 NPs can be further utilized in the preparation of medicine against hepatic and renal diseases, post further clinical and preclinical studies.

Adenosine triphosphatase synergetic cobalt metal-organic frameworks with enhanced peroxidase-like activity for L-cystine detection

The role of metal–organic frameworks (MOFs) in the field of enzyme-like materials is significant, and they have been successfully applied to various peroxidase-like studies involving catalytic oxidation of the substrate 3,3′,5,5′-tetramethylbenzidine (TMB). However, the limited chemical stability of MOFs in aqueous environments hampers their catalytic applications. To address this inherent drawback and enhance the peroxidase-like activity of MOFs, a method involving adenosine triphosphate (ATP) bonding was proposed. In this study, collaborative materials comprising cobalt MOFs (Co-MOFs) and ATP were utilized as model catalysts for TMB catalysis. The presence of ATP significantly improved the catalytic capability of Co-MOFs over a pH range from 3 to 9 and temperatures ranging from 25 to 60 °C. Notably, at pH 7 and 60 °C, the catalytic efficiency increased by approximately 100 times and an impressive enhancement rate of up to 4600% was achieved respectively. This peroxidase-like catalytic system offers a colorimetric detection assay that selectively detects L-cysteine with a limit of detection as low as 76.2 nM. Incorporating ATP into Co-MOFs presents a novel approach for utilizing MOFs in catalysis that is convenient, straightforward, and gentle.

RETRACTION: Protective Effects of Caffeic Acid on Lactate Dehydrogenase Isoenzymes, Electrocardiogram, Adenosine Triphosphatases, and Hematology on Isoproterenol-Induced Myocardial Infarcted Rats.

K. Senthil Kumaran and P. Stanely Mainzen Prince, "Protective Effects of Caffeic Acid on Lactate Dehydrogenase Isoenzymes, Electrocardiogram, Adenosine Triphosphatases, and Hematology on Isoproterenol-Induced Myocardial Infarcted Rats," Journal of Biochemical and Molecular Toxicology 25, no. 2 (2011): 60-67, https://doi.org/10.1002/jbt.20359. The above article, published online on 05 April 2011 in Wiley Online Library (wileyonlinelibrary.com), has been retracted by agreement between the journal Editor-in-Chief, Hari K. Bhat; and Wiley Periodicals, LLC. The retraction has been agreed following an investigation into concerns raised by a third party, which revealed that the western blot in Figure 1 has been published in another article by one of the same authors. The duplicated blots in the two articles represent different experiments. The authors did not provide an explanation or their original data. The editors consider the results and conclusion reported in this article unreliable.

Dr. Manuel Martinez-Maldonado: A Pioneer in Renal Therapeutics and Mentor to a Generation of Minority Physician-Scientists.

Dr. Manuel Martinez-Maldonado is a distinguished Puerto Rican internist, nephrologist, physician-scientist, mentor, and prolific writer whose leadership in academic and clinical settings has significantly advanced the fields of nephrology, renal physiology and pharmacology, fluids and electrolyte metabolism, calcium metabolism, hypertension research, and medical education. His research on electrolyte imbalances has led to innovative hypercalcemia treatments, notably furosemide withIV fluid therapy. This is an approach that, combined with pharmacotherapy using calcitonin and bisphosphonates, became the standard practice for managing hypercalcemia until specific therapies became available. His nephrology research team and laboratory in the San Juan VA (Veterans Affairs) Medical Center and the Medical School of the University of Puerto Rico were internationally renowned. Throughout his career, he fostered a culture of mentorship while spearheading superb clinical teaching and research initiatives. His transformative tenures at several institutions, including Baylor College of Medicine; the University of Puerto Rico-Medical Sciences Campus; the VA medical centers in Atlanta, Houston, and San Juan; Emory University; Oregon Health Sciences University; Ponce School of Medicine; and the University of Louisville School of Medicine demonstrate his lasting contributions to medical science and education. His interdisciplinary approach, advocacy for kidney and clinical research, and contributions to understanding the renin-angiotensin system and the role of sodium-potassium-activated adenosine triphosphatase in renal concentration mechanisms illustrate his enduring impact on renal physiology and human health.

Role and Regulatory Mechanism of circRNA_14820 in the Proliferation and Differentiation of Goat Skeletal Muscle Satellite Cells.

Skeletal muscle satellite cells (SMSCs), a type of myogenic stem cell, play a pivotal role in postnatal muscle regeneration and repair in animals. Circular RNAs (circRNAs) are a distinct class of non-coding RNA molecules capable of regulating muscle development by modulating gene expression, acting as microRNAs, or serving as protein decoys. In this study, we identified circ_14820, an exonic transcript derived from adenosine triphosphatase family protein 2 (ATAD2), through initial RNA-Seq analysis. Importantly, overexpression of circ_14820 markedly enhanced the proliferation of goat SMSCs while concomitantly suppressing their differentiation. Moreover, circ_14820 exhibited predominant localization in the cytoplasm of SMSCs. Subsequent small RNA and mRNA sequencing of circ_14820-overexpressing SMSCs systematically elucidated the molecular regulatory mechanisms associated with circ_14820. Our preliminary findings suggest that the circ_14820-miR-206-CCND2 regulatory axis may govern the development of goat SMSCs. These discoveries contribute to a deeper understanding of circRNA-mediated mechanisms in regulating skeletal muscle development, thereby advancing our knowledge of muscle biology.

Vacuolar H+-ATPase determines daughter cell fates through asymmetric segregation of the nucleosome remodeling and deacetylase complex.

Asymmetric cell divisions (ACDs) generate two daughter cells with identical genetic information but distinct cell fates through epigenetic mechanisms. However, the process of partitioning different epigenetic information into daughter cells remains unclear. Here, we demonstrate that the nucleosome remodeling and deacetylase (NuRD) complex is asymmetrically segregated into the surviving daughter cell rather than the apoptotic one during ACDs in Caenorhabditis elegans. The absence of NuRD triggers apoptosis via the EGL-1-CED-9-CED-4-CED-3 pathway, while an ectopic gain of NuRD enables apoptotic daughter cells to survive. We identify the vacuolar H+-adenosine triphosphatase (V-ATPase) complex as a crucial regulator of NuRD's asymmetric segregation. V-ATPase interacts with NuRD and is asymmetrically segregated into the surviving daughter cell. Inhibition of V-ATPase disrupts cytosolic pH asymmetry and NuRD asymmetry. We suggest that asymmetric segregation of V-ATPase may cause distinct acidification levels in the two daughter cells, enabling asymmetric epigenetic inheritance that specifies their respective life-versus-death fates.