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[This corrects the article DOI: 10.1371/journal.pgph.0005933.].
Cellulose, a primary component of plant cell walls, is synthesized by cellulose synthase complexes (CSCs) at the plasma membrane. Targeting this process with cellulose biosynthesis inhibitors (CBIs) has significantly advanced our understanding of plant cell wall formation and provided valuable compounds for herbicide development. Here, we identified a fungal natural product, 8-methyldichlorodiaporthin (MDD), as a broad-spectrum plant CBI. Structure-activity relationship analyses demonstrate that methylation modifications on the isocoumarin ring and chlorination of the side chain are crucial for MDD-induced growth inhibition. A chemical forward genetic screen in Arabidopsis thaliana revealed two semidominant CESA1 mutations, causing A903T and H1024Y substitutions, that confer insensitivity to MDD. Both mutations locate to transmembrane domains of CESA1, and we show that MDD depletes CSCs from the plasma membrane and reduces cellulose content. Further genetic analyses indicate that the cesa1mddi1-1 A903T mutant also confers resistance to CBIs quinoxyphen and C17, but not to CBIs isoxaben, indaziflam, or ES20. Stacking additional point mutations conferring resistance to other CBIs, cesa3ixr1-1 G998D, and cesa6es20-r3 G935E into the cesa1mddi1-1 A903T background yields multiple-drug-resistant lines that maintain normal growth. These findings establish MDD, as a natural CBI that likely targets CESA1, thereby extending our understanding of CSC regulation and abilities to develop multidrug-resistant crop varieties. These findings offer unique perspectives for weed management and plant biotechnology.
Fertilization is crucial for enhancing soil fertility and crop yields, primarily by modifying soil physicochemical properties and microbial communities, which subsequently influence soil carbon storage. Due to the unique flooded conditions of rice cultivation, paddy soils exhibit distinct microbial compositions and carbon storage mechanisms compared to upland soils. However, indiscriminate fertilization, without a thorough understanding of the underlying soil carbon pool storage and turnover mechanisms, not only yields suboptimal results but also poses environmental risks. Currently, a comprehensive literature review exploring the impacts of fertilization on crop growth and soil fertility accumulation mechanisms within rice cultivation systems remains lacking. This review summarizes the nutrient characteristics and turnover mechanisms in paddy soils, revealing slower organic matter turnover and stable soil organic carbon due to the unique paddy soil anaerobic environment. Microbial mineralization and organic matter accumulation vary with the planting cycle. We discuss the impacts of fertilization on soil fertility and microbial communities, highlighting the superior and more environmentally friendly effects of organic fertilizers. Importantly, a saturation threshold exists for soil carbon storage; exceeding this limit renders fertilization ineffective. Appropriate fertilizer application positively impacts microbial communities by modifying soil pH and physicochemical properties. Furthermore, this paper elaborates on the mechanisms of microbial-mediated carbon sequestration and its influencing factors. Future research leveraging a clear understanding of paddy soil nutrient mechanisms should integrate synthetic biology, materials engineering, and data-driven intelligent decision-making systems. This approach promises to be an effective pathway toward achieving intelligent, green, and high-yielding rice cultivation.
Despite its importance in patient care, public awareness of histopathology and the role of histopathologists remain overshadowed. This study aimed to assess Jordanians' public awareness of histopathology and identify areas of misconception or lack of understanding. A cross-sectional survey was conducted among adults (>18 years) in Jordan through a web-based questionnaire. The survey evaluated participants' knowledge and perceptions of histopathology, including the nature of histopathologists' work, their educational requirements, and their role in patient care. Descriptive statistics, Chi-square tests, and multivariate linear regression were used to analyze the data. A total of 614 participants completed the survey, of which 41% did not recognize histopathology as a medical specialty. The majority identified pathologists as medical doctors whose main job is diagnosis of diseases among living patients, while some participants have misconceptions about associating histopathologists' work with performing autopsies or laboratory tests. Underestimation of the duration of training required to become a certified histopathologist and misconceptions regarding the diagnostic decision-making on selected sample procedures were noticed. Female gender, educational level, and medical background were associated with higher knowledge scores. Despite acceptable general knowledge, the observed misconceptions and lack of understanding regarding histopathology among the public necessitate interdisciplinary collaboration between pathologists and other healthcare professionals to increase the public awareness.
Steroid hormones influence affective behavior and its underlying neural networks. However, distinguishing between organizational and activational hormonal effects, along with effects of socialization, remains challenging, limiting the understanding of the mechanisms underlying affective neurobehavioral differences. Individuals with differences in sex development (DSD), such as congenital adrenal hyperplasia (CAH) and complete androgen insensitivity syndrome (CAIS), offer a unique opportunity to examine how alterations in prenatal steroid hormone exposure have a role in shaping brain development and human behaviors. This review aims to examine how, and to what extent CAH and CAIS, can inform broader neuroendocrine mechanisms of affective behavior. It starts with an overview of experimental psychology and human imaging work on the role of steroid hormones in affective behavior, highlighting the main challenges in the field in human research, and the rationale for including CAH and CAIS. It then summarizes findings from behavioral studies, experimental psychology, and neuroimaging research in CAH and CAIS to discuss how this research contributes to the understanding of the organizational role of steroid hormones on affective outcomes. Although the current evidence is limited and heterogeneous, this review highlights the contribution of prenatal hormonal variability, particularly prenatal androgen exposure, in shaping affective behavior and underlying neural networks. It also highlights how steroid hormones, chromosomal sex, timing of hormonal exposure, developmental stage and psychosocial factors interact in influencing affective outcomes. Advancing this work through neuroimaging and standardized experimental paradigms has the potential to specify the mechanistic pathways through which steroid hormone variability influences behavior. This work can also inform targeted interventions and support emotional well-being and quality of life for individuals with CAH and CAIS.
Hormone receptor-positive/HER2-negative advanced breast cancer (ABC) is a heterogeneous and dynamic disease. Endocrine therapy (ET) + cyclin-dependent kinase 4/6 inhibitors remain the standard-of-care first-line therapy for ABC. However, the treatment landscape is rapidly evolving as our understanding of the complex biology underlying this common subtype advances. Predicting how a patient's cancer might respond to ET across lines of therapy and understanding optimal sequencing in clinical practice are key unmet needs. A range of established and emerging clinical characteristics and biomarkers, including endocrine receptor expression, presence of specific mutations (e.g., ESR1, PIK3CA), and visceral disease, are currently used to guide treatment decisions. However, international guidelines have variable definitions of ET resistance and sensitivity, making delivery of individualized care in clinical practice challenging. Considering this unmet need and leveraging the existing evidence for both prognostic and predictive markers of therapeutic response, we propose that idea of ET suitability be used as a complement to ET resistance and sensitivity. We consider ET suitability to be the clinical assessment of whether a patient could benefit from ET, where benefit is defined not solely by tumor response but by a clinically relevant constellation of characteristics and markers possibly predicting the durability of disease response and symptom control. Several unresolved questions remain regarding issues such as disease heterogeneity, optimal treatment sequencing, and biomarker precision, but further work and ongoing studies will help to support the evolution of guidelines and provide clarity around the effective application of this quickly developing field to daily clinical practice.
Cyanobacteria are photoautotrophic microorganisms that fix CO2 through oxygenic photosynthesis during the day and rely on heterotrophic metabolism at night. In nature, the availability of inorganic carbon (Ci) is often limited, posing a major constraint on photosynthetic efficiency. To overcome this, cyanobacteria have evolved a sophisticated CO2-concentrating mechanism (CCM) that enhances the catalytic performance of the primary carboxylating enzyme, ribulose-1,5-bisphosphate carboxylase/oxygenase (RubisCO). The CCM functions by elevating intracellular CO2 concentrations around RubisCO to suppress its oxygenase activity and enhance CO2 fixation efficiency. Central to this system is the carboxysome, a proteinaceous microcompartment that encapsulates RubisCO and carbonic anhydrase, facilitating efficient conversion of bicarbonate (HCO3 -) to CO2 and its subsequent fixation. This is complemented by multiple Ci transporters that mediate active uptake of CO2 and HCO3 -. Five major transport systems have been characterized: two specialized NDH-1 complexes for CO2 transport and its conversion into HCO3 -, and SbtA, BicA, and BCT1 for HCO3 - uptake. Recent structural studies on CCM uptake systems have revealed key mechanisms of HCO3 - transport, CO2 hydration and transport coupling. These insights provided a deeper understanding of how these systems enhance Ci acquisition and maintain photosynthetic efficiency across diverse environmental conditions and various CO2 regimes. Moreover, the CCM is tightly regulated at both transcriptional and post-translational levels to balance energy usage and carbon demand. This review outlines our current insights into the molecular architecture, transport dynamics, and regulatory networks of the cyanobacterial CCM, emphasizing its critical role in photosynthesis and its potential as a model for bioengineering enhanced CO2 fixation or for engineering synthetic bacterial microcompartments.
Youth ice hockey is a popular sport worldwide. Because of its high physical demand and full contact nature of the game, injuries are common. Adolescent athletes, specifically those nearing the peak height velocity (PHV), represent a vulnerable subset of patients with particular susceptibility to musculoskeletal injuries. Despite the concerns for athlete health, the overall incidence of injuries continues to rise. To review current literature on common orthopedic injuries in youth ice hockey athletes with particular emphasis on mechanisms and pathology related to those during PHV. Current literature was surveyed focusing on epidemiology, injury mechanisms, and pathology of orthopedic injuries observed commonly in youth ice hockey athletes. Special attention was given to injuries related to skeletal immaturity, physeal injuries, apophysitis/overuse injuries, and size mismatch among similarly aged cohorts. Extremity injuries remain common with upper extremity involvement occurring more often than lower extremity injuries. During PHV, changes in limb length result in muscle imbalance and altered neuromuscular control. In addition, the open physis remains weakened. These developmental changes, combined with high collision forces, size mismatch in similarly aged cohorts, and increased skating volume, amplify injury risk. Adolescents during PHV represent a vulnerable subset of patients with increased risk of orthopedic injuries. Understanding growth-related risk factors-physeal susceptibility, size mismatch, and sport demand-is essential to developing injury prevention strategies and directing future research on athlete safety during development.
Adherence of hemodialysis (HD) patients to medical instructions is considered crucial for a longer life expectancy and better quality of life. There is solid evidence that nonadherence (NA) of HD patients' correlates with morbidity and mortality. Despite severe consequences, noncompliance with their medical regimen is the norm for HD patients rather than the exception. NA factors have become one of the top priorities for doctors, healthcare policymakers, and payers alike. Understanding the risk factors for NA is necessary for identifying patients at risk of NA. Factors associated with NA to fluid restriction among HD patients have been explored in many studies; however, most of these were conducted in Western countries and have produced inconsistent results. Regardless the importance of this topic there is remarkable paucity in the studies which identify factors associated with NA to fluid restriction in Saudi Arabia. HD patients are well suited for studying those factors, because they have a number of features that characterizes their lifestyle and put them at an increased risk of NA to fluid restriction including prolonged, intensive treatment and their medical regimens are clear cut and easily determined with objective measures. To determine factors related to NA to fluid restriction among HD patients in Makkah, Saudi Arabia. a cross sectional design in which a sample of 361 HD patients were randomly selected from HD centers in three governmental hospitals in Makkah, individuals were assessed for adherence using the ESRD-AQ questionnaire in addition to clinical examination and laboratory investigation, these methods were used to determine factors related to their NA to fluid restriction. Younger (< 30 years), unmarried, non-Saudis, those with chronic diseases other than hypertension (HTN) & Diabetes Mellitus (DM) and those with long dialysis duration (60+months) were found more likely to be NA to fluid restriction p<0.05. Patients who had factors associated with NA to fluid restriction deserve special attention and support to improve their adherence behavior.
Advances in spatially resolved technologies enable the simultaneous acquisition of diverse data modalities within a tissue slice while preserving critical spatial context, which presents unprecedented opportunities to decipher intricate tissue heterogeneity. However, existing computational approaches lack the intrinsic flexibility to universally process both spatial multi-modal and multi-omics data. Here, we introduce STransformer, a unified deep learning framework designed to seamlessly accommodate a comprehensive landscape of spatial data. By simultaneously capturing short-range cellular interactions and tissue-wide semantic patterns, it extracts robust representations to accurately dissect complex tissue heterogeneity. Systematic evaluations across diverse species, tissue types, and data modalities highlight its profound versatility. For spatial multi-modal data, STransformer delineates intricate anatomical structures in the human cortex, uncovers pathological mechanisms in Alzheimer's disease, and characterizes dynamic spatiotemporal developmental trajectories during chicken cardiogenesis. Scaling to spatial multi-omics data, STransformer synergizes spatial transcriptomic and proteomic profiles to decipher intricate immune microenvironments within the human tonsil, and jointly analyzes spatial epigenomic and transcriptomic data to infer regulatory mechanisms in the mouse embryonic brain. Consequently, STransformer serves as a highly versatile and robust analytical framework for advancing our understanding of tissue heterogeneity and disease pathogenesis.
Parkinson's disease (PD) is a progressive neurological disorder characterized by motor and non-motor symptoms, including olfactory dysfunction, which may precede motor manifestations by up to 10-20 years. Given the role of olfaction in flavor perception and dietary behavior, olfactory impairment may significantly affect nutritional status and quality of life in individuals with PD. This opinion article discusses the relationship between olfactory dysfunction and dietary habits in PD, highlighting the scarcity and inconsistency of the available evidence. While some studies suggest that lower diet quality and reduced intake of specific nutrients are associated with worse olfactory performance, others found no significant correlations. We argue that these inconsistencies largely reflect methodological limitations. Future studies should adopt supervised data collection, validated olfactory tests, and culturally adapted dietary tools. Clarifying whether specific dietary patterns influence olfactory performance or whether olfactory impairment drives inappropriate eating behaviors is essential for better understanding disease progression and informing clinical strategies aimed at improving symptoms, nutritional status, and quality of life in people living with PD.
BackgroundWomen's futsal has experienced significant growth, highlighting the importance of understanding psychological need satisfaction and burnout as key determinants of athlete well-being. Basic psychological needs satisfaction, according to Self-Determination Theory, and athlete burnout are key constructs in promoting healthy and sustainable sports environments. Foot injuries are also prevalent in high-intensity sports such as Futsal and may be related to psychological outcomes in athletes.ObjectivesThis study aimed to examine the relationship between psychological need satisfaction and burnout in female futsal players, and to explore associations between foot and ankle injuries (podiatric pathology), age, and sport experience with these psychological variables.DesignObservational, cross-sectional, descriptive study.MethodsNinety-four adult female futsal players from first and second national divisions participated. Participants completed a sociodemographic and injury questionnaire, the Athlete Burnout Questionnaire (ABQ), and the Psychological Needs in Sport Questionnaire (PNSQ-15). Injury history included ankle sprains, plantar fasciitis, Achilles tendinopathy, fifth metatarsal fractures, and anterior cruciate ligament ruptures. Data were analyzed using descriptive and correlational statistics.ResultsThe majority of players (85%) reported previous injuries, with ankle sprains (73.4%) and plantar fasciitis (35.1%) being most common. PNSQ-15 scores indicated high activation and concentration, with moderate confidence and motivation. Greater age and sport experience were associated with higher concentration and motivation. ABQ scores were moderate overall; more weekly training hours were associated with lower burnout in the dimensions of reduced sense of accomplishment and sport devaluation. Players with plantar fasciitis showed higher burnout scores, particularly in reduced sense of accomplishment (p=0.036).ConclusionFemale futsal players showed favorable psychological skills and moderate levels of burnout. Age, sport experience, and training load were associated with some psychological dimensions, while the presence of certain foot injuries was related to higher burnout scores. These findings suggest that psychological need satisfaction, training load, and injury history are interrelated factors influencing burnout and psychological well-being in female futsal players. Female futsal is growing rapidly, making it important to understand the psychological and physical factors that affect players’ well-being and performance. This study looked at how satisfaction of basic psychological needs such as feeling competent, connected, and autonomous relates to burnout, a state of emotional and physical exhaustion caused by prolonged stress. We also examined whether foot and ankle injuries influence burnout or psychological well-being. Ninety-four adult female futsal players completed questionnaires about their psychological skills, burnout levels, and previous injuries. Most players (85%) had experienced injuries, with ankle sprains and plantar fasciitis being the most common. Overall, players reported good psychological skills, especially in concentration and motivation. More experienced players showed better psychological outcomes. Players who trained more hours per week tended to have lower burnout, suggesting that regular engagement in sport can be protective. However, players with chronic foot injuries, like plantar fasciitis, showed higher burnout levels, indicating that persistent pain may negatively affect well-being. These findings highlight the importance of supporting both the psychological and physical health of female futsal players. Coaches and sports organizations should consider strategies that promote psychological skills, prevent injuries, and provide support for players dealing with chronic pain to maintain well-being and enhance performance.
The Genetics Society of America Mentorship Award recognizes members of the scientific community for exceptional mentoring of geneticists at any career stage. Irini Topalidou is the inaugural recipient in the nonfaculty category, honored for her outstanding contributions to mentoring within the C. elegans community and beyond. She has mentored numerous trainees who have gone on to pursue graduate and medical degrees, postdoctoral or faculty positions, and careers in biotech. The award further acknowledges her published work on STEM education and career choice, as well as her commitment to understanding and addressing trainee challenges and to improving mentorship practices. In the essay below, Irini reflects on her journey as an immigrant in the United States and how these experiences have shaped her life, career, and approach to mentorship. She also highlights how recent scientific and cultural shifts are challenging the principles of openness, diversity, and discovery in the United States, placing one of its greatest strengths at risk.
Long-term alendronate use has been associated with tendinopathies and ligament disorders that may result in chronic pain and functional impairment. Platelet-rich plasma (PRP) therapy has emerged as a regenerative treatment option for chronic tendinopathies by promoting tissue healing and improving pain and function. A 61-year-old woman with an athletic lifestyle took alendronate for 14 years for osteopenia before she stopped taking it. Nine years later, she reported chronic right hamstring complex pain and loss of function after sustaining a lifting injury. She underwent conservative therapy, including stretching exercises and physical therapy and had an evaluation by an orthopedic surgeon. Her pain and function did not improve. She was referred to an interventional pain management physician who diagnosed her with chronic semimembranosus tendinopathy. She was initially treated with a 3-injection series of 12.5% dextrose prolotherapy which did not provide lasting pain relief nor lasting functional improvement. Her treatment was then changed to a holistic regimen of ultrasound-guided leukocyte-poor platelet-rich plasma injections, a post platelet-rich plasma physical therapy program, and acupuncture. This holistic treatment program enabled her to attain 90%-95% pain relief and a significantly improved functional status and quality of life. Platelet-rich plasma injection therapy is an evolving area in Medicine. It holds much promise for those in need of musculoskeletal repair, pain relief and improved function without the need for surgery or chronic use of medications. Much work remains to be done in developing more standardization of platelet-rich plasma therapy, but medical specialists are moving in the right direction as we become more sophisticated and attune in studying, understanding and implementing the potential that platelet-rich plasma injection therapy holds for healing. Incorporation of leukocyte-poor platelet-rich plasma using holistic treatment of chronic semimembranosus tendinopathy associated with chronic use of alendronate was much more effective for pain reduction and restoration of function as compared to only more conservative therapies of physical therapy, stretching exercises, acupuncture, and dextrose prolotherapy.
Postpartum family planning (PPFP) within 12 months after childbirth is crucial to prevent unintended pregnancies and ensure healthy birth spacing for better maternal and child health outcomes. As Millennials and Generation Z dominate the reproductive-age population, understanding how generational identity intersects with socioeconomic factors is critical to designing equitable reproductive health interventions. To assess socioeconomic inequality and identify key determinants of PPFP utilization among Millennial and Generation Z women in Indonesia. We conducted a cross-sectional analysis using data from the 2023 Indonesia Health Survey, a nationally representative dataset. The sample included women aged 15-49 who had given birth in the past five years. Respondents were grouped into two cohorts: Millennials (born 1981-1996) and Generation Z (born 1997-2012). Logistic regression identified determinants of PPFP use, while socioeconomic inequality was assessed using the concentration index and decomposition analysis. Among Millennial women, PPFP utilization was significantly associated with maternal and partner education, employment status, household wealth, parity, pregnancy intention, delivery-related factors, and access to maternal health services. In contrast, among Generation Z women, PPFP utilization was mainly associated with partner's education, employment status, household wealth, delivery complications, and service access, while parity and pregnancy intention were not significant. Socioeconomic inequality in PPFP use was more pronounced among Millennials (CI = -0.069, p<0.001) than Generation Z (CI = -0.024, p=0.313). Generational differences were associated with differences in PPFP determinants and equity patterns, underscoring the potential value of generation-sensitive approaches to promote more equitable access.
Accurate and reliable 3D scene reconstruction is a key component of intelligent surgery, enabling enhanced spatial understanding and data-driven analysis in minimally invasive surgery (MIS). However, existing clinical systems are often bulky and workflow-incompatible, while vision-based Structure-from-Motion methods struggle with sparse textures and specularities, leading to unstable pose estimation and high computational cost. To address these limitations, we present SurGSplat++, a progressive, pose-free Gaussian splatting framework for monocular surgical scene reconstruction that requires no auxiliary hardware or pre-computed camera poses. Experiments show that SurGSplat++ achieves improved geometric stability, reduced pose drift, and superior novel-view synthesis compared with existing approaches. By producing accurate and consistent 3D reconstructions, the proposed method provides a practical solution for post-operative analysis, pre-operative planning, and data-driven surgical modeling in clinical environments. Code will be released at https://surgsplus.github.io/.
Edema formation and ascites are common features in liver disease. The excessive accumulation of body water is caused by increased kidney water retention; yet the mechanisms linking liver and kidney function remain incompletely understood. This review explores the emerging concept of a liver-kidney axis, with bile acids (BAs) as potential mediators for kidney water handling. In cholestatic liver disease, as seen in liver cirrhosis, impaired hepatic BA flow to the duodenum elevates systemic BA concentrations, which can modulate signaling pathways through the BA receptors Farnesoid X Receptor (FXR, NR1H4) and G-protein-coupled bile acid receptor 1 (TGR5, GPBAR1), thereby increasing kidney Na+ and water retention in experimental models. Moreover, BAs can directly activate the sodium channel ENaC in isolated mouse collecting ducts and in mouse distal colon epithelial cells. Thus, BAs can promote sodium and water retention in parallel with the classical sodium- and water-retaining systems, such as the renin-angiotensin-aldosterone system. This effect may potentially contribute to water retention in pregnancy-associated conditions and in proteinuric kidney diseases, where liver function is affected, e.g., by loss of plasma proteins, altering hepatic BA metabolism. In this review, we will describe the synthesis of BAs, their modifications, and kidney BA metabolism in health and disease, and highlight a potential dynamic interplay between liver and kidney function, mediated in part by BAs, with implications for understanding and treating water retention disorders.
Binocular integration is a well-established feature of neuronal processing in the primary visual cortex, where such integration is thought to first emerge. However, accumulating evidence demonstrates that subcortical retinorecipient nuclei possess sophisticated binocular processing capabilities, with important implications for cortical function, visual behavior, and non-imaging-forming physiology. This review synthesizes our current understanding of the circuit origins and functional relevance of binocular integration and modulation in the dorsal lateral geniculate nucleus, superior colliculus, and other subcortical targets. We describe how the definition of binocularity has evolved beyond simple ocular dominance to encompass diverse modes of neuronal modulation, including facilitation, summation, suppression, and emergent responses. We highlight the prevalence of multiple wiring motifs subserving binocular convergence, including direct retinal inputs, lateral circuits via local interneurons, feedback from cortical or subcortical sources, and indirect relays through intra- or interhemispheric connections. Recent anatomical and functional studies reveal substantial binocular integration despite apparent eye-specific input segregation, with region- and species-specific differences reflecting distinct ethological demands. Finally, elucidation of a critical role for subcortical binocular processing in prey capture and threat responses is expanding our cortex-centric view and revealing new complexity in the regional distribution of visual computations essential for survival behaviors.
The spread of ESBL-producing Escherichia coli strains among different hosts, including humans, domestic animals, and synanthropic animals, has become a current public health challenge. A comprehensive analysis of bacterial isolates in animals and meat products throughout South America is essential to improve the understanding of their distribution and the different mechanisms of resistance in developing countries. This review aims to evaluate the different studies on ESBL-producing E. coli in animals and meat products in South America, from 2020 to 2024. A systematic search was conducted in databases such as PubMed, SciELO, and Latindex from January 1, 2020 to May 1, 2024. Studies published in English, Spanish, and Portuguese on ESBL-producing E. coli from animal sources (dogs, cats, chickens, pigs, cows, rats, and meat products) were conducted across South America. Eighty percent of the included articles reported blaCTX-M genes, with the blaCTX-M-2 gene being the most common with 48.2%. This gene was found mainly in chickens, followed by dogs, cows and pigs. The ST10 clone was the most prevalent, reported in 40% of the included studies, while ST155 was evidenced in 30%. Other clones, such as ST117 and ST131, were identified in 20% of the studies. The increasing prevalence of blaCTX-M resistance genes in E. coli in South American countries highlights the need for effective surveillance and control measures in the animal environment. The inappropriate use of antibiotics in livestock requires multidisciplinary approaches, such as the One Health approach, to address this problem.
ZMYND11 is the sole known reader of H3.3K36me3. It has been characterized as a transcriptional repressor that fine-tunes RNA polymerase II (Pol II) elongation through recognition of gene body-localized H3K36me3, based primarily on earlier ChIP-seq data showing predominant ZMYND11 occupancy at gene bodies. However, subsequent data suggest that ZMYND11 may also localize to promoter regions. Here, using CUT&Tag assay, we demonstrate that ZMYND11 robustly occupies promoter regions in mouse ESCs and MEFs, with its promoter enrichment positively correlating with gene expression levels and Pol II occupancy. We further identify formaldehyde crosslinking as a critical factor causing signal loss at transcription start sites in conventional ChIP-seq. Mechanistically, ZMYND11 deficiency reduces the pausing index of Pol II, H3.3, and H3K36me3, indicating impaired transcription initiation. ZMYND11 knockout in mouse ESCs induces transcriptomic changes, impairs cell proliferation, and aberrantly activates 2-cell-specific transcriptional programs via ROS accumulation. Our findings reveal a previously unappreciated role for ZMYND11 as a transcriptional initiator that stabilizes Pol II at promoters, establishing its essential function in maintaining embryonic stem cell homeostasis and advancing our understanding of its context-dependent transcriptional regulatory mechanisms.