Search PubMed⌕ Search

SEARCH · Search PubMed

Results for “Veronica”

Search indexed PubMed citations on genomics, clinical trials, systematic reviews and public health. Explore titles, authors and supplied subject terms, then open the PubMed record.

Quote a phrase for an exact phrase match. Source license links do not imply unrestricted reuse.

33 records · Page 2Linked to original sources
PubMed2026

A reproducible three-dimensional model of human brain tissue to investigate physiological and disease-associated microglia phenotypes.

Stem-cell-based in vitro models offer promising potential to elucidate human brain cell functions and interactions, but limitations in reproducibility, maturation and cell-type diversity persist. Especially, prolonged incorporation of mature microglia and studies of neuroinflammation have proven challenging. Here, we developed a human induced pluripotent stem cell-based three-dimensional cortical brain tissue model (3BTM) containing neurons, astrocytes and microglia with high reproducibility, maturity and viability. 3BTMs show morphological, functional and proteomic maturation of all cell types, leading to high similarity to their in vivo counterparts. Incorporated microglia survive for over 6 months and display mature morphology, functions and gene expression. Importantly, when engineered to model Alzheimer's disease pathology, 3BTMs recapitulate key disease hallmarks, including amyloid deposition, increased phospho-tau levels and neuroinflammation, with microglia shifting their transcriptional landscape to disease-relevant signatures. Treatment of Alzheimer's disease 3BTMs with anti-Aβ immunotherapy cleared deposits and largely reversed disease signatures in glia. Together, our microglia-containing model provides a platform for studying physiological and pathological states of human brain tissue.

Humans↗
PubMed2026

KDM6A loss enhances oxidative phosphorylation uncovering tissue-level convergent evolution.

The tumor suppressor KDM6A/UTX, a histone demethylase and a 2-oxoglutarate-dependent dioxygenase, is frequently lost in many cancer types. We show that KDM6A loss pervasively activates oxidative phosphorylation in several solid tumors, generating a pseudo-hyperoxic environment, opposite from the pseudo-hypoxia observed in VHL-mutated renal carcinomas. Mechanistically, KDM6A sustains the expression of the coil-coil domain gene CCDC3, which inhibits CREB1-driven transcription of the mitochondrial regulator PPARGC1A. In the hematological cancer multiple myeloma where KDM6A is frequently deleted, its loss similarly promotes oxidative phosphorylation, but via an alternative mechanism: the increased transfer of mitochondria from stromal to myeloma cells via tunneling nanotubes, triggered by the loss of the mTORC1 inhibitor TRAF3IP3. Beyond cancer, KDM6A regulates oxidative phosphorylation also during development and in adult tissues, engaging either the CCDC3-CREB1 or the TRAF3IP3-mTORC1 pathways. These mutually exclusive associations suggest a tissue-level convergent evolution, positioning KDM6A as a central modulator of mitochondrial activity through context-specific partners.

Journal Article↗
PubMed2026

Catecholaminergic polymorphic ventricular tachycardia mediated by ryanodine receptor 2: a validated risk stratification.

BACKGROUND AND AIMS: Patients with catecholaminergic polymorphic ventricular tachycardia (CPVT) are at risk for potentially life-threatening arrhythmic events (AEs) even while treated with β-blockers. The aim was to develop a model for individualized prediction of AEs in patients with RYR2-mediated CPVT on β-blocker monotherapy. METHODS: The derivation and independent validation cohorts included 743 and 129 patients, respectively. AEs were defined as arrhythmic syncope, appropriate implantable cardioverter-defibrillator shock, sudden cardiac arrest (SCA), and sudden cardiac death. Near-fatal or fatal AEs (nf/fAEs) included all AEs except for arrhythmic syncope. Prediction models using Cox regression were developed and internally and externally validated. RESULTS: A total of 102 (13.7%) patients in the derivation cohort and 24 (18.6%) patients in the validation cohort experienced ≥1 AE over a median follow-up of 5.1 [interquartile range (IQR), 7.7] and 2.4 (IQR, 4.4) years, respectively. Predictors of AE were arrhythmic syncope or SCA prior to diagnosis and age at β-blocker initiation. In the derivation and validation cohorts, the optimism-corrected C-indices of the models for AE were 0.67 [95% confidence interval (CI) 0.62-0.72] and 0.59 (95% CI 0.48-0.71), respectively. For nf/fAEs, ventricular arrhythmia severity before β-blocker initiation was a fourth independent predictor, and C-indices of the models in the derivation and validation cohorts were 0.74 (95% CI 0.68-0.80) and 0.60 (95% CI 0.47-0.72), respectively. In the derivation cohort, calibration slopes were 1.00 (95% CI 0.59-1.41) for AE and 1.00 (95% CI 0.69-1.32) for nf/fAE. CONCLUSIONS: These externally validated risk prediction models using clinical parameters accurately distinguished CPVT patients on β-blocker monotherapy at low and high risk for future AEs while treated with β-blockers. These models provide guidance for implementation of clinical management therapies to prevent AEs in patients with CPVT.

Humans↗
PubMed2025

The genetic basis of chloride exclusion in grapevines.

Mediterranean regions are among the most important areas for global grape production, characterized by dry climates and frequent challenges associated with soil salinity. In these environments, chloride toxicity is a major factor limiting vine growth and fruit quality. Despite the critical role of chloride exclusion in salinity tolerance, the genetic mechanisms underlying this trait remain poorly understood. In this study, we analyzed natural variation in chloride exclusion using a diverse panel of 335 accessions representing 18 wild and cultivated Vitis species. This panel, comprising accessions from the southwestern United States and Mexico, captures a broad range of evolutionary adaptations to abiotic stress and provides a valuable genetic resource for breeding efforts aimed at introducing novel traits. Using genome-wide association and quantitative trait loci (QTL) mapping, we identified a major QTL on chromosome 8, now designated qClEx8.1, containing candidate genes encoding cation/H⁺ exchangers (CHXs), which are involved in ion transport and homeostasis. To validate these findings, we analyzed a mapping population derived from Vitis acerifolia longii 9018 and the commercial rootstock GRN3, confirming the chromosome 8 locus as a major determinant of chloride exclusion. Structural variant analysis revealed nonsynonymous substitutions within CHX genes that may influence protein function and salinity tolerance. Additionally, we discovered a novel QTL on chromosome 19 enriched with G-type lectin S-receptor-like serine/threonine-protein kinases, known regulators of stress signaling. By integrating phenotypic and genomic data across a diverse Vitis collection, this study advances our understanding of the genetic architecture underlying chloride exclusion and highlights candidate genes for breeding salt-tolerant rootstocks.

Vitis↗
PubMed2024

MucR protein: Three decades of studies have led to the identification of a new H-NS-like protein.

MucR belongs to a large protein family whose members regulate the expression of virulence and symbiosis genes in α-proteobacteria species. This protein and its homologs were initially studied as classical transcriptional regulators mostly involved in repression of target genes by binding their promoters. Very recent studies have led to the classification of MucR as a new type of Histone-like Nucleoid Structuring (H-NS) protein. Thus this review is an effort to put together a complete and unifying story demonstrating how genetic and biochemical findings on MucR suggested that this protein is not a classical transcriptional regulator, but functions as a novel type of H-NS-like protein, which binds AT-rich regions of genomic DNA and regulates gene expression.

Bacterial Proteins↗
PubMed2025

Identification of EppR, a Second Repressor of Error-Prone DNA Polymerase Genes in Acinetobacter baumannii.

Acinetobacter baumannii is an opportunistic pathogen causing several infections that are increasingly difficult to treat due to its ability to rapidly gain antibiotic resistances. These resistances can arise due to mutations through the activity of error-prone DNA polymerases, such as DNA polymerase V (DNA Pol V) in response to DNA damage. The regulation of the DNA damage response (DDR) in A. baumannii is not completely understood; the regulation of genes encoding multiple copies of DNA Pol V is not fully characterized. Through genome-wide mutagenesis, we have identified a novel TetR-like family regulator of the umuDC and umuC genes, which we have named Error-prone polymerase regulator (EppR). We have found that EppR represses the expression of the genes encoding DNA Pol V and itself through direct binding to an EppR motif in their promoters. Lastly, we show that EppR also regulates UmuDAb, previously identified as a regulator of genes encoding DNA Pol V. These two gene products are functionally required to ensure regulation of the expression of the two umuDC, the two umuC genes as well as the regulators umuDAb and eppR genes. With these results, we propose a model in which multiple transcription factors regulate the expression of all these genes.

Acinetobacter baumannii↗
PubMed2026

Defective EV-mediated transport of SHH alters neural fate specification in EPM1 epilepsy.

The extracellular milieu, including extracellular vesicles (EVs), plays a pivotal role in brain development. In this study, we sought to elucidate the pathogenesis of progressive myoclonus epilepsy type 1 (EPM1), a disease caused by mutations in the CSTB gene, using cerebral organoids (COs) derived from patient cells. The results demonstrate that EPM1 COs display increased electrophysiological activity and disrupted excitatory/inhibitory (E/I) balance. Single-cell RNA sequencing analysis of ventral EPM1-COs revealed an abnormal specification of progenitor fate, with a shift toward dorsal neuron identities. We demonstrated that this misspecification is driven by a functional alteration of the ventral signaling niche, resulting from impaired EV dynamics and altered protein cargo. Mechanistically, we identified Sonic Hedgehog (SHH) as a direct physical interactor of CSTB and demonstrated that CSTB deficiency leads to reduced SHH content and secretion. Our findings establish CSTB as a safeguard of ventral patterning and identify the CSTB-SHH-EV axis as a potential therapeutic target for mitigating the E/I imbalance associated with EPM1.

Hedgehog Proteins↗
PubMed2025

The Streptococcus pyogenes mannose phosphotransferase system (Man-PTS) influences antimicrobial activity and niche-specific nasopharyngeal infection.

Streptococcus pyogenes is a human-adapted pathogen that can cause multiple diseases, including pharyngitis and skin infections. Although this bacterium produces many virulence factors, how S. pyogenes competes with the host microbiota is not well understood. Here, we detected antimicrobial activity from S. pyogenes MGAS8232 that prevented the growth of Micrococcus luteus. This activity was produced when cells were grown in 5% CO2 in M17 media supplemented with galactose; however, the addition of alternative sugars coupled with genome sequencing experiments revealed that the antimicrobial phenotype was not related to classical bacteriocins. To further determine genes involved in the production of this activity, a transposon mutant library in S. pyogenes MGAS8232 identified the mannose phosphotransferase system (Man-PTS), a major sugar transporter, as important for the antimicrobial phenotype. Loss-of-function transposon mutants linked to the antimicrobial activity were identified to also be involved in alternative sugar utilization, and additionally, the Man-PTS was further identified from an inadvertent secondary mutation in a bacteriocin operon mutant. Sugar utilization in the Man-PTS mutants demonstrated that galactose, mannose, and N-acetylglucosamine utilization was impaired. RNA-seq experiments in high and low glucose concentrations further characterized the Man-PTS as a glucose transporter; however, transcriptional regulators or virulence factors were not affected with the loss of the Man-PTS. Deletion of Man-PTS demonstrated defects in a mouse model of nasopharyngeal infection but not skin infection. This work suggests that the ability of S. pyogenes to utilize alternative sugars presented by glycans may play a role in acute infection and interactions with the endogenous microbial population existing in the nasopharynx.IMPORTANCEStreptococcus pyogenes is responsible for over 500,000 deaths per year primarily due to invasive infections and post-infection sequelae, although the most common manifestations include pharyngitis and impetigo. S. pyogenes can adapt to its environment through alternative sugar metabolism. Here, we identified an antimicrobial phenotype that was not bacteriocin-related but a by-product of alternative sugar metabolism. The mannose phosphotransferase system was involved in the production of the antimicrobial and was also important for S. pyogenes to utilize alternative sugars and establish nasopharyngeal infection but not skin infection. Overall, this study identified potential strategies used by S. pyogenes for interactions with the endogenous microbiota and further elucidated the importance of sugar metabolism in acute upper respiratory tract infection.

Streptococcus pyogenes↗
PubMed2026

Nucleoporins in Cancer: Functional Roles and Therapeutic Opportunities.

UNLABELLED: The nuclear pore complex (NPC) and its building-block proteins, nucleoporins (NUP), play fundamental roles in maintaining cellular fitness by regulating nucleocytoplasmic transport, chromatin and transcriptional activity, and genome stability. These core biological processes are critical for cancer cells, and thus, tumor-driven co-option of NUP-regulated functions has emerged as an important mechanism contributing to the pathogenesis of multiple malignancies. This review discusses how NUP dysregulation mechanistically contributes to tumor initiation and progression and how these insights open opportunities for innovative anticancer therapies, including using clinical-grade molecular glues that induce selective NUP degradation and pharmacologically inhibiting NPC-regulated epigenomic/transcriptomic signaling and nucleocytoplasmic transport. SIGNIFICANCE: Recent studies demonstrate that NUPs play fundamental roles in cancer pathogenesis by dysregulating key NPC functions and driving tumorigenesis and disease progression. NUPs and NPC-regulated mechanisms can be pharmacologically targeted, providing a strong rationale for developing much-needed innovative therapeutic strategies to combat cancer.

Journal Article↗
PubMed2026

Trade-Off Between Early Reperfusion and First-Pass Effect With Tenecteplase Versus Alteplase Before Stroke Thrombectomy.

BACKGROUND: Early reperfusion and first-pass effect are key procedural end points in large-vessel occlusion stroke thrombectomy. Because of greater fibrin specificity, tenecteplase may achieve higher early reperfusion rates compared with alteplase, yet impact of thrombolytic agents on first-pass effect remains unclear. METHODS: Consecutive patients with anterior circulation large-vessel occlusion stroke receiving intravenous thrombolysis before endovascular treatment at 2 US stroke centers were reviewed. Early reperfusion was defined as extended Thrombolysis in Cerebral Infarction ≥2b50 on initial angiography. First-pass effect was defined as extended Thrombolysis in Cerebral Infarction 2c-3 after a single pass. Multivariable logistic regression identified predictors of early reperfusion and first-pass effect. Ordinal logistic regression assessed associations of thrombolytic agent, early reperfusion, and first-pass effect with 90-day modified Rankin Scale shift. RESULTS: Among 299 patients (tenecteplase 201, alteplase 98), early reperfusion occurred in 60 (20.1%) and was more frequent with tenecteplase compared with alteplase (24.4% versus 11.2%; adjusted odds ratio [OR], 2.31 [95% CI, 1.07-4.98]). Patients without early reperfusion were evaluated for first-pass effect. Of 237 patients, first-pass effect was less frequent with tenecteplase compared with alteplase (30.3% versus 40.2%; adjusted OR, 0.42 [95% CI, 0.23-0.79]). Early reperfusion and first-pass effect each independently predicted better functional outcome, but functional outcomes were similar between tenecteplase and alteplase overall. CONCLUSIONS: We observed higher early reperfusion rates with tenecteplase, but greater first-pass effect with alteplase, while functional outcomes were comparable. This may suggest that the early reperfusion advantage of tenecteplase could be offset by downstream procedural variables such as first-pass effect, highlighting the importance of jointly evaluating both reperfusion and procedural efficiency when comparing thrombolytic strategies.

Humans↗
PubMed2025

Distinct Behavioral Profiles and Neuronal Correlates of Heroin Vulnerability Versus Resiliency in a Multi-Symptomatic Model of Heroin Use Disorder in Rats.

OBJECTIVE: The behavioral and diagnostic heterogeneity within the opioid use disorder (OUD) diagnosis is not readily captured in current animal models, limiting the translational relevance of the mechanistic research that is conducted in experimental animals. The authors hypothesized that a nonlinear clustering of OUD-like behavioral traits would capture population heterogeneity and yield subpopulations of OUD vulnerable rats with distinct behavioral and neurocircuit profiles. METHODS: Over 900 male and female heterogeneous stock rats, a line capturing genetic and behavioral heterogeneity present in humans, were assessed for several measures of heroin use and rewarded and non-rewarded seeking behaviors. A nonlinear stochastic block model clustering analysis was used to assign rats to OUD vulnerable, intermediate, and resilient clusters. Additional behavioral tests and circuit analyses using c-fos protein activation were conducted on the vulnerable and resilient subpopulations. RESULTS: OUD vulnerable rats exhibited greater heroin taking and seeking behaviors relative to those in the intermediate and resilient clusters. Akin to human OUD diagnosis, further vulnerable rat subclustering revealed subpopulations with different combinations of behavioral traits, including sex differences. Lastly, heroin cue-induced neuronal patterns of circuit activation differed between resilient and vulnerable phenotypes. Behavioral sex differences were recapitulated in patterns of circuitry activation, including preferential engagement of extended amygdala stress circuitry in males and cortico-striatal drug cue-seeking circuitry in females. CONCLUSION: Using a nonlinear clustering approach in rats, the analysis captured behavioral diagnostic heterogeneity reflective of human OUD diagnosis. OUD vulnerability and resiliency were associated with distinct neuronal activation patterns, posing this approach as a translational tool in assessing neurobiological mechanisms underpinning OUD.

Animals↗
PubMed2025

Leprosy relapse after multidrug therapy: Systematic review and meta-analysis.

OBJECTIVE: To synthesize the scientific evidence regarding the prevalence of leprosy relapse following multidrug therapy. METHOD: A systematic review was conducted following the JBI methodology for prevalence studies and reported according to the guidelines, with the registration number CRD42020177141. The inclusion criteria were based on the mnemonics (Population, Condition, Context). Population: Individuals of any age or sex diagnosed with leprosy relapse and previously treated with paucibacillary or multibacillary multidrug therapy. Conditions: Leprosy relapse after multidrug therapy, measured as the proportion of cases. Context: Studies conducted within the healthcare service settings. The databases searched included Medline, Latin American and Caribbean Health Sciences Literature (LILACS), Embase, Cumulative Index to Nursing and Allied Health Literature (CINAHL), Scopus, WoS, and Caribbean Public Health Agency (CARPHA). The references were managed using Mendeley. A random-effects meta-analysis model was employed, and heterogeneity was assessed using Higgins' I² statistics. RESULTS: Of 26 studies (a combined sample of 71,385 participants), 19 were included in the meta-analysis. A higher prevalence of relapse was observed in working-age males, multibacillary cases with a high bacillary load, and those with established physical disabilities. The estimated prevalence of relapse across studies ranged from 0% to 10%, with a pooled estimate of 4% in India (95% CI: 0.03-0.05). The overall point estimate for relapse using regular multidrug therapy was 0.04 (95% CI: 0.02-0.05). CONCLUSION: The prevalence of relapse varied according to the geographic location and type of multidrug therapy, with substantial heterogeneity across studies. These findings suggest that factors such as individual patient characteristics, treatment adherence, and capacity for healthcare services may have influenced the outcomes observed in this review.

Humans↗
PubMed2024

Tobacco, nicotine, and cannabis use and exposure in an Australian Indigenous population during pregnancy: A protocol to measure parental and foetal exposure and outcomes.

BACKGROUND: The Australian National Perinatal Data Collection collates all live and stillbirths from States and Territories in Australia. In that database, maternal cigarette smoking is noted twice (smoking <20 weeks gestation; smoking >20 weeks gestation). Cannabis use and other forms of nicotine use, for example vaping and nicotine replacement therapy, are nor reported. The 2021 report shows the rate of smoking for Australian Indigenous mothers was 42% compared with 11% for Australian non-Indigenous mothers. Evidence shows that Indigenous babies exposed to maternal smoking have a higher rate of adverse outcomes compared to non-Indigenous babies exposed to maternal smoking (S1 File). OBJECTIVES: The reasons for the differences in health outcome between Indigenous and non-Indigenous pregnancies exposed to tobacco and nicotine is unknown but will be explored in this project through a number of activities. Firstly, the patterns of parental and household tobacco, nicotine and cannabis use and exposure will be mapped during pregnancy. Secondly, a range of biological samples will be collected to enable the first determination of Australian Indigenous people's nicotine and cannabis metabolism during pregnancy; this assessment will be informed by pharmacogenomic analysis. Thirdly, the pharmacokinetic and pharmacogenomic findings will be considered against maternal, placental, foetal and neonatal outcomes. Lastly, an assessment of population health literacy and risk perception related to tobacco, nicotine and cannabis products peri-pregnancy will be undertaken. METHODS: This is a community-driven, co-designed, prospective, mixed-method observational study with regional Queensland parents expecting an Australian Indigenous baby and their close house-hold contacts during the peri-gestational period. The research utilises a multi-pronged and multi-disciplinary approach to explore interlinked objectives. RESULTS: A sample of 80 mothers expecting an Australian Indigenous baby will be recruited. This sample size will allow estimation of at least 90% sensitivity and specificity for the screening tool which maps the patterns of tobacco and nicotine use and exposure versus urinary cotinine with 95% CI within &#xb1;7% of the point estimate. The sample size required for other aspects of the research is less (pharmacokinetic and genomic n = 50, and the placental aspects n = 40), however from all 80 mothers, all samples will be collected. CONCLUSIONS: Results will be reported using the STROBE guidelines for observational studies. FORWARD: We acknowledge the Traditional Custodians, the Butchulla people, of the lands and waters upon which this research is conducted. We acknowledge their continuing connections to country and pay our respects to Elders past, present and emerging. Notation: In this document, the terms Aboriginal and Torres Strait Islander and Indigenous are used interchangeably for Australia's First Nations People. No disrespect is intended, and we acknowledge the rich cultural diversity of the groups of peoples that are the Traditional Custodians of the land with which they identify and with whom they share a connection and ancestry.

Adult↗