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PubMed1979

Light-induced calcium release in isolated intact cattle rod outer segments upon photoexcitation of rhodopsin.

By applying flash-spectrophotometry with the calcium-indicating dye arsenazo III rapid light-triggered calcium release in various cattle rod outer segment preparations was studied. It is shown that light-induced calcium signals can be unambiguously discriminated from underlying absorption changes due to photolysis of rhodopsin and apparent absorption changes resulting from lightscattering transients. The following results have been obtained: 1. Calcium-induced arsenazo III responses can be quantitatively and kinetically resolved within the time domain of the visual transduction process. 2. Photoexcitation of rhodopsin results in calcium release from intradiscal binding sites. 3. Calcium released does not appear in the cytoplasmic space unless the disc membrane is made permeable to calcium ions by an ionophore. 4. The shortest observed half-rise time of calcium release (300 ms) is possibly limited by the ionophore. 5. The stoichiometric ratio of calcium released/rhodopsin bleached is 0.5 at a free calcium concentration of 2 microM. The amount of calcium released is proportional to the precentage of rhodopsin bleaching (from 1--10%). 6. Upon disruption of the disc stack by lysis of intact rod outer segments the light-induced calcium release is greatly altered. The results are discussed in relation to previous reports on a light-induced calcium release from retinal discs and in terms of the proposed role of calcium as an intracellular transmitter in vertebrate photoreceptors.

Animals↗

PubMed2026

Mitochondrial homeodynamics in ageing: mechanisms, resilience, and interventions.

Mitochondria integrate bioenergetics, redox signalling, calcium handling, biosynthesis, apoptosis, and stress responses. Their contribution to ageing depends less on any single pathway than on the ability to sustain these functions through continuous maintenance, remodelling, and inter-organelle communication. This review proposes mitochondrial homeodynamics as a systems-level framework for that ability, which rests not on static preservation but on three linked capacities. Maintenance safeguards mitochondrial genome, proteome, and membrane integrity. Adaptation adjusts metabolism and remodels network and cristae architecture to match changing demand. Recovery restores function and reserve after challenge. These capacities emerge from mitochondrial quality control, network and cristae remodelling, biogenesis, mitophagy, retrograde stress signalling, and inter-organelle communication. So defined, mitochondrial dysfunction becomes a measurable loss of capacity rather than a descriptive category. Ageing erodes these capacities in tissue- and context-specific ways, which reduces physiological reserve, slows recovery after stress, and amplifies sterile inflammation. The mechanisms underlying these capacities, the biomarkers that report them, and the interventions proposed to preserve them are evaluated in turn. Exercise provides the strongest human evidence for coordinated mitochondrial and functional adaptation, whereas evidence for energy restriction, NAD+ precursors, mitophagy-supporting compounds, and mitochondria-targeted agents remains heterogeneous and endpoint-specific. No mitochondrial intervention has been shown to slow ageing or extend lifespan in healthy humans, and movement of a biomarker towards a younger reference value does not establish rejuvenation. Progress will require dynamic measures of maintenance, adaptation, and recovery, obtained in defined tissues and interpreted alongside clinically meaningful outcomes.

Humans↗

PubMed2026

Phosphoproteomic Analysis of Cortical Tissue from Mice Lacking Both CaMKIIα and CaMKIIβ Identifies Novel In Vivo Substrates.

Ca2+/calmodulin-dependent protein kinase II (CaMKII) plays a critical role in calcium signaling. Several studies have shown that mice with single Camk2a or Camk2b gene knockouts are viable, yet exhibit distinct phenotypes, whereas the double knockout of both genes is lethal. These findings indicate that each gene can have distinct roles and that they also partially compensate for each other in yet unknown essential brain functions. In order to provide insight into potential novel CaMKII functions, we performed parallel phosphoproteomic analyses on nonstimulated cortex tissues from inducible Camk2a and Camk2b double knockout (Camk2af/f;Camk2bf/f;CAG-CreESR) mice and from wild type mice. A total of 5622 phosphorylated peptides derived from 2080 proteins were identified. Phosphorylation at serine/threonine residues in 130 proteins was downregulated in the double knockout mice, including residues in 113 proteins that have not previously been identified as potential CaMKII substrates. Comparison of amino acid sequences surrounding the downregulated phosphorylation residues provided new insights into the CaMKII-substrate consensus sequences in vivo. This data set provides an important resource for future studies examining novel roles for CaMKII in the brain.

Animals↗

PubMed2025

Blood Pressure Genetics in Han Taiwanese With Cross-Trait Analysis in East Asians: Insights Into Comorbidities, All-Cause Mortality, and Cardiovascular Mortality.

BACKGROUND: Hypertension is a major health burden in East Asia. However, the genetic architecture and clinical implications of blood pressure (BP) traits remain underexplored beyond European-focused studies. This large-scale study aimed to investigate hypertension, systolic BP, and diastolic BP, to uncover genetic links to comorbidities and mortality in Han Taiwanese individuals. METHODS: This large-scale study used China Medical University Hospital biobank data and conducted genome-wide association studies on 25 523 hypertension cases and 47 522 controls, plus 66 236 individuals for systolic BP and 66 152 for diastolic BP. Cross-trait genetic correlations were assessed across 5 East Asian biobanks. Mendelian randomization and polygenic risk scores were applied to assess causality and predict clinical outcomes. RESULTS: We identified 8 loci and 36 genes for hypertension, 7 loci and 17 genes for systolic BP, and 9 loci and 26 genes for diastolic BP. ATP2B1 and FGF5 were common to all BP traits, implicating calcium signaling and vascular remodeling pathways. Cross-trait analyses showed shared genetic liability between BP traits and cardiovascular and metabolic comorbidities. Phenome-wide association studies confirmed strong associations with circulatory diseases. Mendelian randomization analyses demonstrated that elevated BP causally increases the risk of unstable angina pectoris. Polygenic risk scores predicted significantly higher risks and earlier onset of unstable angina pectoris, all-cause mortality, and cardiovascular mortality among individuals in the top polygenic risk score quintiles. CONCLUSIONS: Our findings highlight the genetic basis of BP and comorbidities in East Asians, suggesting that BP genetic risk may inform future approaches to early risk assessment and prevention.

Aged↗

PubMed2026

Disentangling Sex Differences in Sulfonylurea Drug Response With Genome-Wide Association Studies in Individuals With Type 2 Diabetes.

Sulfonylureas are a cornerstone of type 2 diabetes therapy despite interindividual variability in response. Despite well-documented sex-based differences, pharmacogenomic and genome-wide association studies (GWAS) have largely overlooked sex as a biological variable. We conducted the first sex-stratified GWAS of hemoglobin A1c (HbA1c) response to sulfonylureas in Action to Control Cardiovascular Risk in Diabetes (ACCORD) clinical trial participants (N = 871). Variants meeting genome-wide (P < 5.0 × 10-8) and suggestive (P < 5.0 × 10-6) significance were assessed for replication in the Pharmacogenomics of Metformin (PMET1) cohort. Replicated variants were further analyzed in the Study to Understand the Genetics of the Acute Response to Metformin and Glipizide in Humans (SUGAR-MGH) cohort to assess acute insulin and glucose responses to a single glipizide dose. Genome-wide significant loci with sex-specific effects were identified: KAZN, KIF2B, SLC39A10, and SPINK5 (combined-sex); CRACR2A, KCNK2, and TENM2 (male-only); and NACPH2 (female-only). Two suggestive variants in the TMEM64/NECAB1 locus, associated with reduced HbA1c response to sulfonylureas in the male-only ACCORD analysis, were directly replicated in the PMET1 male-only cohort. In SUGAR-MGH, one replicated variant (rs6471250-C) was significantly associated with reduced peak insulin in males (P = 0.035) but not females (P = 0.40), demonstrating sex-specific functional effects. This study identified statistically supported and biologically plausible loci with prior evidence linking nearby genes to pathways relevant to sulfonylurea action, including insulin secretion, insulin regulation/sensitivity, calcium signaling, potassium-channel biology, and glucose transport. The findings highlight sex-specific differences in sulfonylurea response, providing mechanistic insights and underscoring the importance of sex-specific precision medicine. Identification of genetic variants influencing sex-specific response could inform dosing to optimize sulfonylureas.

Humans↗

PubMed2026

MicroRNA-mRNA Networks in Skeletal Muscle of Tailored Pig Models for Dystrophinopathies.

BACKGROUND: Duchenne muscular dystrophy (DMD) and Becker muscular dystrophy (BMD) are X-linked dystrophinopathies caused by mutations in the dystrophin (DMD) gene. A common DMD-causing mutation in humans is exon 52 deletion (DMDΔ52), which disrupts the reading frame and abolishes dystrophin expression. Therapeutic skipping of exon 51 or 53 can restore the reading frame, producing a truncated but functional protein and generating a BMD-like phenotype. Porcine models recapitulating DMDΔ52 (DMD) and DMDΔ51-52 (BMD-like) were used to identify molecular differences and condition-specific miRNA-mRNA networks. METHODS: Skeletal muscle (triceps brachii) from four DMD, four BMD, and five wild-type (WT) pigs at 3.5 months of age underwent stranded total RNA-seq and small RNA-seq. Differentially expressed mRNAs (|log2FC| ≥ 1, adj. p ≤ 0.05) and miRNAs (adj. p ≤ 0.05) were identified with DESeq2. miRNA-mRNA networks were constructed using RNAhybrid predictions (MFE < -25 kcal/mol, seed pairing) filtered by inverse Pearson correlation. RESULTS: Compared with WT, DMD muscle exhibited 1440 upregulated and 487 downregulated genes, characterized by strong repression of structural, contractile, calcium-handling and metabolic genes (e.g., MYBPC2, MYL3, MYLK2, CACNA2D3, CACNA2D4) and marked upregulation of inflammatory mediators and innate immune receptors (e.g., IL6, IL18, IL1R1, CCR1/2/5, TLR1/2/4/7/9). In contrast, BMD muscle showed partial restoration of these pathways and clustered closer to WT in global expression profiles. Distinct miRNA signatures were observed between DMD and BMD. Differential expression analysis identified 22 upregulated and 12 downregulated miRNAs in DMD versus WT and 36 upregulated and 21 downregulated miRNAs in BMD versus WT. Integration of miRNA and mRNA data yielded extensive regulatory networks (1013 unique pairs for upregulated miRNAs in DMD; 2679 pairs for downregulated miRNAs in BMD). Two condition-specific miRNAs emerged as strong biomarker candidates: ssc-miR-296-3p (upregulated exclusively in DMD, targeting 228 genes enriched in muscle structure and fatty acid metabolism) and ssc-miR-423-5p (elevated specifically in BMD, targeting 67 genes involved in calcium signalling and tissue development). Several dysregulated miRNAs, including miR-199a-5p and miR-199b, overlapped with those reported in human DMD and other muscular dystrophies. CONCLUSIONS: Exon 51 skipping in the DMDΔ52 background partially restores key transcriptional programmes in skeletal muscle but does not fully normalize them to WT patterns. The identification of condition-specific miRNAs highlights post-transcriptional regulatory differences between DMD and BMD, positioning them as promising biomarkers and therapeutic targets. These findings underscore the translational value of porcine dystrophinopathy models for mechanistic studies and preclinical evaluation of RNA-targeted interventions.

Animals↗

PubMed2026

Transcriptomic insights into temperature regulation of proliferation and differentiation in skeletal muscle cells of Nibea albiflora.

Myogenesis involves sequential stages of muscle satellite cell activation, myoblast proliferation, differentiation, and fusion into multinucleated myotubes. Teleost muscle exhibits indeterminate growth and is highly sensitive to environmental temperature, yet the underlying mechanisms by which temperature regulate proliferation and differentiation remain poorly understood. In this study, we established a primary skeletal muscle cell culture from the yellow drum (Nibea albiflora), an economically important marine fish, and integrated morphological observations with comparative transcriptomics analysis to characterize cellular and molecular responses at 28 °C and 20 °C during both proliferation and differentiation stages. Phenotypic analysis revealed that 28 °C significantly enhanced both myoblast proliferation and myogenic differentiation ability compared with 20 °C. Transcriptomic profiling revealed that at 28 °C, differentiation upregulated extracellular matrix(ECM) organization, calcium signaling, and sarcomere assembly, while proliferation enhanced focal adhesion, growth factor signaling, and lipid metabolism. At 20 °C, differentiation was characterized by glutathione metabolism, and ferroptosis, while proliferation involved cytokine-cytokine receptor interaction and negative regulation of signal transduction. Core myogenic regulatory factors (MRFs), particularly myogenin, were strongly upregulated at 28 °C during the differentiation stage, serving as an internal control. Based on these findings, we propose a testable model that elevated temperature coordinates Ca2+-dependent MRF activation with ECM-integrin signaling to drive sarcomere assembly and muscle growth. Key differentially expressed genes (DEGs) regulating myogenesis in N. albiflora were also identified. This study provides a mechanistic framework for temperature adaptation in teleost skeletal muscle and identifies candidate genes for functional validation and marker-assisted selection, as well as a rationale for temperature management strategies to improve aquaculture yield of N. albiflora.

Animals↗

PubMed2025

Deleterious, protein-altering variants in GSPT2 are putatively associated with an X-linked neurodevelopmental disorder with intellectual disability, language impairment, autism, and epilepsy.

PURPOSE: Approximately 6% of individuals with neurodevelopmental disorders are predicted to be X-linked, and the GSPT2 gene, located at Xp11.22, has not yet been associated with any Mendelian disease. METHODS: To establish genotype-phenotype associations between GSPT2 and neurodevelopmental disorders, clinical investigations were performed in unrelated individuals, genomic and functional studies were conducted on the participants' blood and heterologous cell system. RESULTS: We described 6 individuals from 6 unrelated families carrying hemizygous variants in GSPT2 with intellectual disability, delayed speech and language development, autism spectrum disorder, epilepsy, or abnormal fetal neurodevelopment. Structural molecular modeling revealed significant deleterious effects of the identified variants. GSPT2 is preferentially enriched in the brain and cerebellum compared with other tissues. GSPT2-deficient H4 neuroglioma cells slow down the proliferation and downregulate the expression of cell-cycle-related genes. Transcriptomics revealed that GABAergic and calcium-signaling-related genes were significantly downregulated in GSPT2-deficient cells. Consistent with the transcriptomic data, RT-PCR analysis verified the marked downregulation of critical genes (CACNA1B, etc) in GSPT2-knockout cells and further confirmed these findings with proteomic profiling. CONCLUSION: Our data suggest a putative GSPT2-related X-linked neurodevelopmental disorders through dysregulation of cell-cycle progression and calcium/GABAergic signaling pathways.

Humans↗

PubMed2026

Deciphering S-nitrosylation-regulated metabolic networks in postmortem beef based on label-free modificomics: Identification of ferroptosis as a novel quality-related pathway.

This study elucidated the molecular mechanisms of S-nitrosylation on postmortem beef metabolism and quality based on the label-free modificomics. Varying degrees of S-nitrosylation were exogenously induced in beef semimembranosus (SM) muscle. Results indicated that a high S-nitrosylation level significantly increased beef pH and Warner-Bratzler shear force (WBSF) while reducing centrifugal loss (P < 0.05). A total of 828 S-nitrosylated proteins and 1458 modification sites were identified, of which 114 sites on 81 proteins (DSNPs) exhibited differential modification abundance, representing an increase of 125% compared with previous proteomics studies. DSNPs were mainly involved in glycolysis, the tricarboxylic acid cycle, oxidative phosphorylation, calcium signaling, cell structure, and ferroptosis. Notably, this study provides the first evidence in postmortem muscle that S-nitrosylation regulates key ferroptosis-related proteins, including ACSL, CP, and TF, offering new insights into the link between S-nitrosylation and the ferroptosis pathway in meat. Correlation analysis demonstrated that TF was significantly negatively correlated with pH and WBSF, but positively correlated with centrifugal loss (P < 0.05). Collectively, protein S-nitrosylation critically modulates postmortem beef quality through the coordinated regulation of multiple metabolic processes. More importantly, the identification of ferroptosis as a S-nitrosylation-sensitive pathway provides a new perspective for regulating meat quality through protein post-translational modifications.

Animals↗

PubMed2017

Surface PD-L1, E-cadherin, CD24, and VEGFR2 as markers of epithelial cancer stem cells associated with rapid tumorigenesis.

Cancer cells require both migratory and tumorigenic property to establish metastatic tumors outside the primary microenvironment. Identifying the characteristic features of migratory cancer stem cells with tumorigenic property is important to predict patient prognosis and combat metastasis. Here we established one epithelial and two mesenchymal cell lines from ascites of a bladder cancer patient (i.e. cells already migrated outside primary tumor). Analyses of these cell lines demonstrated that the epithelial cells with surface expression of PD-L1, E-cadherin, CD24, and VEGFR2 rapidly formed tumors outside the primary tumor microenvironment in nude mice, exhibited signatures of immune evasion, increased stemness, increased calcium signaling, transformation, and novel E-cadherin-RalBP1 interaction. The mesenchymal cells on the other hand, exhibited constitutive TGF-β signaling and were less tumorigenic. Hence, targeting epithelial cancer stem cells with rapid tumorigenesis signatures in future might help to combat metastasis.

B7-H1 Antigen↗

PubMed2025

Genomic study for pregnancy loss in Brahman cattle.

Reproduction has major influence on productivity of beef cattle operations. Maintaining an animal in the herd for an extended period without producing a marketable product can result in significant economic losses, compromising the efficiency of the production system. Understanding genetic variation's role in pregnancy loss (PL) is crucial for improving reproductive success in cattle. Identifying genomic regions that influence embryo and fetal survival, as well as pinpointing candidate genes associated with PL, can enhance breeding strategies. The objective of this study was to estimate variance components and investigate genetic factors associated with PL in Brahman cattle. Phenotypic records consisted of 29,905 pregnancy (28,691) and abortion (1,214) records from nulliparous, primiparous, and multiparous cows. A total of 921 animals were genotyped using a medium-density SNP chip (∼52K markers). Variance components were estimated using a threshold model to assess the binary response to PL through a single-step genomic BLUP procedure. The heritability estimate for PL was low (0.11), but the presence of genetic variance suggests that selection for improved reproductive performance is feasible. Genome-wide association analyses identified 17 candidate regions containing 92 genes. Regions on BTA4, 7, 8, 9, 11, 12, 16, 18, 19, 21, 22, and 29 harbored genes associated with embryonic development and implantation, fertilization, G protein-coupled receptors, embryonic brain development, olfactory receptor activity, and calcium signaling. Orthologous genes were also identified in humans (Homo sapiens), rats (Rattus norvegicus), and mice (Mus musculus). The candidate regions reported in this study provide insights for identifying and selecting animals with improved reproductive performance, ultimately enhancing the productivity of Brahman cattle. Moreover, our findings contribute to a better understanding of the genetic and physiological mechanisms underlying pregnancy retention in beef cattle.

Animals↗

PubMed2026

Integrated analysis of gut microbiota, serum metabolomics, and proteomics reveals novel associations with clinical symptoms in patients with cerebral infarction.

BACKGROUND: Cerebral infarction (CI) is a major cause of adult disability and mortality worldwide. Mounting evidence supports the critical role of the gut-brain axis in cerebrovascular disease progression. This study aimed to characterize the alterations in gut microbiota, serum metabolome, and serum proteome in patients with CI, and to identify multi-omics signatures associated with clinical symptoms. METHODS: A total of 20 CI patients and 20 healthy controls (HC) were enrolled. Fecal microbiota was profiled using 16 S rRNA gene high-throughput sequencing. Serum metabolomics and proteomics were analyzed using ultra-high-performance liquid chromatography-tandem mass spectrometry (UPLC-MS/MS) and data-independent acquisition (DIA) proteomics, respectively. Spearman correlation and multi-omics integration were applied to explore the associations among microbiota, metabolites, proteins, and clinical indicators. RESULTS: CI patients displayed significant gut microbiota dysbiosis, with a markedly lower gut microbiota health index (GMHI) and higher microbiota disorder index (MDI) compared with HC (P < 0.001). The genera g_norank_o_RF39 and Oxalobacter were significantly enriched in CI patients, whereas Clostridium_sensu_stricto_1 and Agathobacter were enriched in HC. Metabolomic analysis identified 445 differential metabolites, mainly involved in glycerophospholipid metabolism, phenylalanine metabolism, and caffeine metabolism. Proteomic analysis revealed 140 differentially expressed proteins linked to inflammatory responses, calcium signaling, and NF-κB signaling. Multi-omics integration showed that signature gut microbiota was strongly correlated (P < 0.005) with key serum metabolites and proteins implicated in CI pathogenesis. CONCLUSIONS: This integrated multi-omics study revealed distinct gut microbiota, serum metabolomic, and proteomic alterations in CI patients. The microbiota-metabolite-protein regulatory axes provide novel insights into the gut-brain axis in CI and may serve as potential diagnostic biomarkers or therapeutic targets.

Humans↗

PubMed2026

Screening of core targets for Di(2-ethylhexyl) Phthalate-related gastric cancer based on machine learning, molecular docking, and SHAP analysis.

PURPOSE: Given the existing uncertainties regarding the link between Di(2-ethylhexyl) phthalate (DEHP) exposure and gastric cancer (GC) progression, this study aimed to clarify their association, identify the toxic targets of DEHP, and elucidate the underlying molecular mechanisms. METHODS: Multiple integrated approaches were employed, including Gene Expression Omnibus (GEO) data analysis, network toxicology, molecular docking, and machine learning. STRING and Cytoscape tools were utilized to identify key targets, while Gene Ontology (GO) and Kyoto Encyclopedia of Genes and Genomes (KEGG) enrichment analyses were performed to explore the functional enrichment of intersecting targets. Machine learning and SHAP analysis were applied to screen core targets in GC. Molecular docking was performed to evaluate the binding affinity of DEHP toward core targets, and 200 ns molecular dynamics simulations were further conducted for representative complexes to validate their dynamic stability. RESULTS: A total of 18 key targets were identified using STRING and Cytoscape. GO and KEGG enrichment analyses demonstrated that these intersecting targets were primarily enriched in the extracellular region, as well as the Calcium signaling pathway and cAMP signaling pathway. Through machine learning analyses, 7 key genes (ADRB2, ESRRG, GRIA4, IL13RA2, NR3C2, PLA2G1B, and SULT2A1) were identified as core targets in GC through machine learning analyses. Molecular docking simulations revealed strong binding specificity between DEHP and the target proteins. Among them, NR3C2 and ADRB2 exhibited relatively high predictive importance in the machine learning models. DEHP showed favorable binding affinity toward these core targets, and molecular dynamics simulations further confirmed that ADRB2-DEHP and NR3C2-DEHP complexes maintained stable conformations throughout the simulation. CONCLUSIONS: Our findings identified GC associated genes that were computationally predicted as potential targets of DEHP. These results indicated structural compatibility between DEHP and its target proteins but did not prove that DEHP exposure accounts for the gene expression changes in GC.

Molecular Docking Simulation↗

PubMed2026

Genome-Wide Association Analysis for Growth-Related Traits in Indoor- and Outdoor-Cultured Juvenile Grass Carp (Ctenopharyngodon idella).

Grass carp is a key herbivorous freshwater fish, yet long-term inbreeding reduces growth rates. Current genome-wide association studies (GWAS) primarily focus on a limited range of growth traits, while intestinal morphology is likely to emerge as a promising new proxy for both growth performance and health status. We reared juvenile grass carp from one batch in indoor vs. natural aquatic vegetation groups for 100 days, measuring body weight (BW), length (BL), height (BH), and intestinal length (IL) in 200 individuals (100/group). Phenotypic differences were significant for all traits, with IL most variable. GWAS identified 95 significant SNPs, among which 21 were related to multiple traits. Candidate gene and KEGG pathway analyses linked these SNPs to myogenesis, skeletal development, immunity, calcium signaling, and stress resistance. Twelve SNPs were found to be associated with IL, including 8 multi-trait-related and 4 trait-specific ones. This suggests that IL can serve as a supplementary growth trait. There was no overlap with prior GWAS, but recurrent signals on chromosomes 1, 2, 14 (BW) and 2, 3, 14, 24 (BH) merit further study. Our findings enrich molecular resources for grass carp and highlight IL's potential for marker-assisted breeding.

Ctenopharyngodon idella↗

PubMed2026

Whole-Genome Sequencing Reveals Population Structure, Genetic Diversity, and Selection Signatures in Kazakh Dromedary and Bactrian Camels.

Understanding the genomic basis of environmental adaptation is essential for the conservation and genetic improvement of domestic camels. In this study, we investigated the population structure, genetic diversity, and genomic variation potentially associated with environmental adaptation of Kazakh dromedary and Bactrian camels using whole-genome sequencing. Whole-genome sequencing data were generated for Kazakh camels (15 dromedaries and 16 Bactrian camels) and integrated with 131 publicly available genomes representing camel populations from the Arabian Peninsula, Iran, Xinjiang, Inner Mongolia, and Mongolian wild camels. Population structure, genetic diversity, and genome-wide selection were evaluated using principal component analysis, ADMIXTURE, nucleotide diversity, linkage disequilibrium, runs of homozygosity, genomic inbreeding (FROH), and selection scans based on FST, θπ ratio, and XP-EHH. Population genomic analyses revealed clear differentiation between dromedary and Bactrian camels, whereas Kazakh camel populations exhibited higher nucleotide diversity (θπ = 1.307-1.551 × 10-3), and lower genomic inbreeding (median FROH: 0.037-0.056) than Arabian populations. Genome-wide selection analyses identified MC4R as the prominent candidate gene in Kazakh dromedaries and RYR1 as a prominent candidate gene in Kazakh Bactrian camels. Functional enrichment analyses highlighted pathways related to energy metabolism, thermogenesis, calcium signaling, skeletal muscle function, mitochondrial activity, and oxidative stress response. These findings provide new insights into genomic variation potentially associated with environmental adaptation in Kazakh camels and offer valuable genomic resources for future conservation, breeding, and evolutionary studies.

MC4R↗

PubMed2026

Genome-Wide Characterization of Calmodulin-Binding Transcription Activators Genes in Aegilops tauschii.

Calcium signaling plays a central role in plant adaptation to abiotic stresses and is primarily mediated by calmodulin and its associated transcription factors. Calmodulin-binding transcription activators (CAMTAs) regulate stress-responsive gene expression, but their characteristics and functions remain largely unexplored in Aegilops tauschii Coss., the D-genome progenitor of bread wheat. In this study, a genome-wide identification and characterization of the CAMTA gene family was performed, followed by phylogenetic, structural, conserved domain, promoter cis-element, and expression analyses under drought stress. Five AetCAMTA genes were identified and classified into three phylogenetic groups. All proteins contained conserved CG-1 DNA-binding, ankyrin repeat (ANK), and IQ calmodulin-binding domains and exhibited similar exon-intron organization. Promoter analysis revealed abundant hormone- and stress-responsive cis-elements, particularly abscisic acid-responsive element (ABRE) and drought-responsive MYB-binding site (MBS) motifs, suggesting their involvement in drought-responsive signaling. Quantitative RT-PCR showed genotype- and stress-dependent expression patterns, with the drought-tolerant ecotype (TN-01-1747) exhibiting higher expression of AetCAMTA1, AetCAMTA2, and AetCAMTA3 than the drought-sensitive ecotype (TN-01-1559) under moderate drought stress. These findings provide new insights into the evolutionary and functional characteristics of AetCAMTA genes and identify promising candidates for improving drought tolerance in wheat through molecular breeding and biotechnological approaches.

Gene Expression Regulation, Plant↗

PubMed2026

Blood-based proteomic profiling reveals context-dependent changes in BCL2-associated signaling during taxane therapy in breast cancer patients.

The quality of life for many cancer survivors is compromised due to severe, long-lasting side effects of chemotherapy. As part of a pilot, prospective, non-interventional study to examine the side effects of chemotherapy in breast cancer patients, we examined the change in protein expression in blood collected from patients before and after treatment with taxanes for 12 weeks. Protein expression was measured with reverse phase proteomic arrays (RPPA), which revealed divergent changes in apoptosis, senescence, and calcium signaling-related proteins depending on treatment setting (neoadjuvant vs. adjuvant). The largest change identified was BCL2 (B-cell lymphoma 2), a founding member of the BCL2 family of proteins that regulate apoptosis. Other proteins regulated by BCL2, including RB1 (retinoblastoma protein 1) and NLRP3 (NLR family pyrin domain containing 3) changed significantly over the course of treatment. These differences are consistent with intracellular calcium signaling dysregulation and activation of stress-response pathways that overlap with senescent-associated secretory phenotype (SASP)-like signaling, which has been implicated in cancer recurrence. To contextualize these observations, we generated Kaplan-Meier survival curves using publicly available proteomics data from The Cancer Proteome Atlas (TCPA). This work aims to demonstrate how blood-based proteomics can serve as a non-invasive method to monitor systemic physiological shifts during cancer therapy, offering a framework for generating hypotheses about chemotherapy timing and long-term outcomes.

Humans↗

PubMed2025

Calmodulin D133H Disrupts Cav1.2 and Kv7.1 Regulation to Prolong Cardiac Action Potentials in Long QT Syndrome.

Calmodulin (CaM) plays a central role in cardiac excitation-contraction coupling by regulating ion channels, including the L-type calcium (Ca2+) channel Cav1.2 and the voltage-gated potassium (K+) channel Kv7.1. Mutations in CaM are linked to severe arrhythmogenic disorders such as Long QT syndrome (LQTS), yet the molecular mechanisms remain incompletely understood. Here, we investigate the structural and functional consequences of the arrhythmia-associated CaM variant D133H. Biophysical analysis revealed that D133H destabilises Ca2+ binding at the C-terminal lobe of CaM, altering its Ca2+-dependent conformational changes. Electrophysiological recordings demonstrated that CaM D133H impairs Ca2+-dependent inactivation (CDI) of Cav1.2, prolonging Ca2+ influx, while also reducing activation of Kv7.1, thereby limiting repolarising K+ currents. Together, these dual defects converge to prolong action potential duration, providing a mechanistic basis for arrhythmogenesis in LQTS. Our findings establish that CaM D133H perturbs both Ca2+ and K+ channel regulation, highlighting a shared pathway by which calmodulinopathy mutations disrupt cardiac excitability.

Calmodulin↗