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Recent adaptive radiations provide experimental opportunities to parse the relationship between genomic variation and the origins of distinct phenotypes. Sympatric radiations of the charr complex (genus Salvelinus) present a trove for phylogenetic analyses as charrs have repeatedly diversified into multiple morphs with distinct feeding specializations. However, charr species flocks normally comprise only two to three lineages. Dolly Varden charr inhabiting Lake Kronotskoe represent the most extensive radiation described for the genus, containing at least seven lineages, each with defining morphological and ecological traits. Here, we perform the first genome-wide analysis of this species flock to parse the foundations of adaptive change. Our data support distinct, reproductively isolated lineages within the clade. We find that changes in genes associated with thyroid signaling and craniofacial development provided a foundational shift in evolution to the lake. The thyroid axis is further implicated in subsequent lineage partitioning events. These results delineate a genetic scenario for the diversification of specialized lineages and highlight a common axis of change biasing the generation of specific forms during adaptive radiation., (© 2024. Published by The Company of Biologists Ltd.)

Extracorporeal Membrane Oxygenation (ECMO) has become an essential lifesaving intervention for individuals with severe cardiovascular and respiratory failure. Its application is expanding across several therapeutic contexts, surpassing conventional indications. The COVID-19 pandemic has significantly stressed worldwide health systems to manage acute respiratory failure. ECMO has been employed as a vital intervention, particularly for patients with severe COVID-19-induced acute respiratory distress syndrome (ARDS). ECMO is applicable throughout pregnancy. The principal indications for ECMO in pregnant women align with those in the general population. However, pregnancy complicates issues, necessitating consideration of both mother's and infant's well-being. Patients with systemic rheumatic diseases are prone to experience life-threatening complications. While a majority of these patients respond to immunosuppressive drugs, a small percentage suffer organ failure and may benefit from ECMO as a bridge to recovery. The article addresses coagulation therapies, highlighting the necessity of precise anticoagulation to avert both bleeding and thrombosis, particularly in patients requiring extended ECMO support. Additionally, the pharmacokinetics of antibiotics in ECMO patients are summarized, including the influence of the ECMO circuit on drug metabolism. Survey-based research offers valuable insights into ECMO use, procedures, and challenges. The paper evaluates current survey-based research and ECMO guidelines, highlighting clinical practice, training, and resource availability discrepancies across ECMO centers globally. Particular focus is placed on the rehabilitation requirements of ECMO survivors, acknowledging the importance of early mobilization and post-discharge care in improving long-term outcomes and quality of life., (© 2024. The Author(s), under exclusive licence to Springer-Verlag GmbH Germany, part of Springer Nature.)

Sex chromosomes often differ between closely related species and can even be polymorphic within populations. Species with multifactorial sex determination segregate for multiple different sex determining loci within populations, making them uniquely informative of the selection pressures that drive the evolution of sex chromosomes. The house fly (Musca domestica) is a model species for studying multifactorial sex determination because male determining genes have been identified on all six of the chromosomes, which means that any chromosome can be a "proto-Y". Natural populations of house fly also segregate for a recently derived female-determining locus, meaning house flies also have a proto-W chromosome. The different proto-Y chromosomes are distributed along latitudinal clines on multiple continents, their distributions can be explained by seasonality in temperature, and they have temperature-dependent effects on physiological and behavioral traits. It is not clear, however, how the clinal distributions interact with the effect of seasonality on the frequencies of house fly proto-Y and proto-W chromosomes across populations. To address this question, we measured the frequencies of house fly proto-Y and proto-W chromosomes across nine populations in the United States of America. We confirmed the clinal distribution along the eastern coast of North America, but it is limited to the eastern coast. In contrast, annual mean daily temperature range predicts proto-Y chromosome frequencies across the entire continent. Our results therefore suggest that temperature heterogeneity can explain the distributions of house fly proto-Y chromosomes in a way that does not depend on the cline., (© The Author(s) 2024. Published by Oxford University Press on behalf of The American Genetic Association. All rights reserved. For commercial re-use, please contact reprints@oup.com for reprints and translation rights for reprints. All other permissions can be obtained through our RightsLink service via the Permissions link on the article page on our site—for further information please contact journals.permissions@oup.com.)

Chemotherapy is often combined with immune checkpoint inhibitor (ICIs) to enhance immunotherapy responses. Despite the approval of chemo-immunotherapy in multiple human cancers, many immunologically cold tumors remain unresponsive. The mechanisms determining the immunogenicity of chemotherapy are elusive. Here, we identify the ER stress sensor IRE1α as a critical checkpoint that restricts the immunostimulatory effects of taxane chemotherapy and prevents the innate immune recognition of immunologically cold triple-negative breast cancer (TNBC). IRE1α RNase silences taxane-induced double-stranded RNA (dsRNA) through regulated IRE1-dependent decay (RIDD) to prevent NLRP3 inflammasome-dependent pyroptosis. Inhibition of IRE1α in Trp53 -/- TNBC allows taxane to induce extensive dsRNAs that are sensed by ZBP1, which in turn activates NLRP3-GSDMD-mediated pyroptosis. Consequently, IRE1α RNase inhibitor plus taxane converts PD-L1-negative, ICI-unresponsive TNBC tumors into PD-L1 high immunogenic tumors that are hyper-sensitive to ICI. We reveal IRE1α as a cancer cell defense mechanism that prevents taxane-induced danger signal accumulation and pyroptotic cell death., Competing Interests: Declaration of interests M.F.R. receives research funding from Pfizer and Genentech and consulting fees from Novartis, Seagen, Macrogenics, and AstraZeneca. M.F.R. is the PI of clinical trial NCT03950570. X.C. reports previous research funding from Fosun Pharma. M.J.E. holds patents and receives income from Veracyte on the PAM50-based products, Prosigna., (Copyright © 2024 Elsevier Inc. All rights reserved.)

Prior to the coronavirus disease 2019 (COVID-19) pandemic, Central Asia and Eastern Europe saw a significant rise in international medical student enrollment, driven by competitive tuition fees, prestigious institutions, and culturally diverse environments. The pandemic forced a rapid shift to online learning, disrupting student mobility and compromising clinical training quality. Online education for international medical students during the COVID-19 pandemic has proven beneficial, though low- and middle-income countries struggled with access to information infrastructure and resources. While 64% of students preferred online learning, challenges like limited internet access and lack of in-person interaction persisted, making a blended approach of online and traditional methods most effective. Despite a rebound in post-pandemic enrollment, persistent challenges such as linguistic obstacles, psychological stress, and cultural adaptation issues remain. Active research engagement during undergraduate studies is essential for skill development. Integrating research into education curricula and fostering motivation are crucial for enhancing academic outcomes. Critical thinking and cultural competence are vital, necessitating explicit instruction and collaborative learning strategies. Addressing language barriers through comprehensive support systems for both instructors and students is imperative. Tailored strategies and robust institutional support are essential to enhancing the educational experiences and success of international medical students., Competing Interests: The authors have no potential conflicts of interest to disclose., (© 2024 The Korean Academy of Medical Sciences.)

Rheumatic diseases are chronic conditions that often result in significant physical and psychological challenges, reducing patients' quality of life and increasing the economic burden on healthcare systems. This study examines the vital role of psychological interventions in the comprehensive treatment of rheumatic diseases. The findings reveal a high prevalence of psycho-emotional disorders such as depression, anxiety, and stress among these patients, which can worsen disease progression and hinder treatment adherence. The review highlights the bidirectional relationship between the central nervous and immune systems, showing how psychological stress influences the pathophysiology of inflammatory diseases. Various psychological interventions are explored, including mind-body therapies, cognitive behavioral therapy, acceptance and commitment therapy, and mindfulness-based practices such as meditation, yoga, and tai chi. These approaches improve emotional well-being, help reduce pain, and enhance overall quality of life. The article emphasizes a holistic treatment model incorporating pharmacological care, physical rehabilitation, and psychological support. This integrated approach fosters more effective management of rheumatic diseases by addressing their complex nature and promoting better functional outcomes. The study advocates for the seamless incorporation of psychological support into routine clinical practice tailored to the biopsychosocial profile of each patient. Future research should focus on identifying the most effective psychological interventions for different patient groups to enhance the quality of life for individuals with rheumatic diseases., (© 2024. The Author(s), under exclusive licence to Springer-Verlag GmbH Germany, part of Springer Nature.)

Nurses constitute nearly 50% of the worldwide health workforce, and the World Health Organisation has advocated for an enlargement of their roles to guarantee fair health care and address the increasing need for services. The growing specialization in nursing practice has led to a rise in educational options for nurses, including the growth of PhD programs. These programs play a crucial role in preparing nurse researchers and educators. This growth underlines the importance of evidence-based practice and high-quality academic writing in nursing. The article highlights the importance of nurses' involvement in creating evidence-based practice guidelines. The active engagement of nurses in developing evidence-based practice recommendations is essential to ensure the practicality, relevance, and grounding of these guidelines in real-world clinical experiences. The advancement of nursing depends mainly on using rigorous research procedures to generate, analyze, and disseminate knowledge and data. The current article discusses essential research methodologies, including interviews, surveys, and bibliometric and altmetric analyses. It also aims to tackle concerns about inadequate writing skills, plagiarism, and insufficient comprehension of ethical norms in research and publishing. The recommended strategies to promote nursing research and publications encompass enhancing writing skills through specialized education, embracing open-access publishing, and utilizing social media for broader distribution following publication. Implementing these approaches would increase the quality and impact of nursing publications and reinforce nursing's role in defining health policy and enhancing the care of patients., Competing Interests: The authors have no potential conflicts of interest to disclose., (© 2024 The Korean Academy of Medical Sciences.)

Organisms use constitutive or induced defenses against pathogens and other external threats. Constitutive defenses are constantly on, whereas induced defenses are activated when needed. Each of these strategies has costs and benefits, which can affect the type of defense that evolves in response to pathogens. In addition, induced defenses are usually regulated by multiple negative feedback mechanisms that prevent overactivation of the immune response. However, it is unclear how negative feedback affects the costs, benefits, and evolution of induced responses. To address this gap, we developed a mechanistic model of the well-characterized Drosophila melanogaster immune signaling network that includes 3 separate mechanisms of negative feedback as a representative of the widespread phenomenon of multilevel regulation of induced responses. We show that, under stochastic fly-bacteria encounters, an induced defense is favored when bacterial encounters are rare or uncertain, but in ways that depend on the bacterial proliferation rate. Our model also predicts that the specific negative regulators that optimize the induced response depend on the bacterial proliferation rate, linking negative feedback mechanisms to the factors that favor induction., Competing Interests: Conflicts of interest The author(s) declare no conflicts of interest., (© The Author(s) 2024. Published by Oxford University Press on behalf of The Genetics Society of America.)

Amphibians represent a diverse group of tetrapods, marked by deep divergence times between their three systematic orders and families. Studying amphibian biology through the genomics lens increases our understanding of the features of this animal class and that of other terrestrial vertebrates. The need for amphibian genomic resources is more urgent than ever due to the increasing threats to this group. Amphibians are one of the most imperiled taxonomic groups, with approximately 41% of species threatened with extinction due to habitat loss, changes in land use patterns, disease, climate change, and their synergistic effects. Amphibian genomic resources have provided a better understanding of ontogenetic diversity, tissue regeneration, diverse life history and reproductive modes, antipredator strategies, and resilience and adaptive responses. They also serve as essential models for studying broad genomic traits, such as evolutionary genome expansions and contractions, as they exhibit the widest range of genome sizes among all animal taxa and possess multiple mechanisms of genetic sex determination. Despite these features, genome sequencing of amphibians has significantly lagged behind that of other vertebrates, primarily due to the challenges of assembling their large, repeat-rich genomes and the relative lack of societal support. The emergence of long-read sequencing technologies, combined with advanced molecular and computational techniques that improve scaffolding and reduce computational workloads, is now making it possible to address some of these challenges. To promote and accelerate the production and use of amphibian genomics research through international coordination and collaboration, we launched the Amphibian Genomics Consortium (AGC, https://mvs.unimelb.edu.au/amphibian-genomics-consortium) in early 2023. This burgeoning community already has more than 282 members from 41 countries. The AGC aims to leverage the diverse capabilities of its members to advance genomic resources for amphibians and bridge the implementation gap between biologists, bioinformaticians, and conservation practitioners. Here we evaluate the state of the field of amphibian genomics, highlight previous studies, present challenges to overcome, and call on the research and conservation communities to unite as part of the AGC to enable amphibian genomics research to "leap" to the next level., Competing Interests: Competing interests The authors declare no competing interests.

Cellular metabolism comprises a complex network of biochemical anabolic and catabolic processes that fuel the growth and survival of living organisms. The enzyme malate dehydrogenase (MDH) is most known for its role in oxidizing malate to oxaloacetate (OAA) in the last step of the tricarboxylic acid (TCA) cycle, but it also participates in the malate-aspartate shuttle in the mitochondria as well as the glyoxylate cycle in plants. These pathways and the specific reactions within them are dynamic and must be carefully calibrated to ensure a balance between nutrient/energy supply and demand. MDH structural and functional complexity requires a variety of regulatory mechanisms, including allosteric regulation, feedback, and competitive inhibition, which are often dependent on whether the enzyme is catalyzing its forward or reverse reaction. Given the role of MDH in central metabolism and its potential as a target for therapeutics in both cancer and infectious diseases, there is a need to better understand its regulation. The involvement of MDH in multiple pathways makes it challenging to identify which effectors are critical to its activity. Many of the in vitro experiments examining MDH regulation were done decades ago, and though allosteric sites have been proposed, none to date have been specifically mapped. This review aims to provide an overview of the current knowledge surrounding MDH regulation by its substrate, products, and other intermediates of the TCA cycle while highlighting all the gaps in our understanding of its regulatory mechanisms., (© 2024 The Author(s). Published by Portland Press Limited on behalf of the Biochemical Society.)

The Last Common Ancestor (LCA) is understood as a hypothetical population of organisms from which all extant living creatures are thought to have descended. Its biology and environment have been and continue to be the subject of discussions within the scientific community. Since the first bacterial genomes were obtained, multiple attempts to reconstruct the genetic content of the LCA have been made. In this review, we compare 10 of the most extensive reconstructions of the gene content possessed by the LCA as they relate to aspects of the translation machinery. Although each reconstruction has its own methodological biases and many disagree in the metabolic nature of the LCA all, to some extent, indicate that several components of the translation machinery are among the most conserved genetic elements. The datasets from each reconstruction clearly show that the LCA already had a largely complete translational system with a genetic code already in place and therefore was not a progenote. Among these features several ribosomal proteins, transcription factors like IF2, EF-G, and EF-Tu and both class I and class II aminoacyl tRNA synthetases were found in essentially all reconstructions. Due to the limitations of the various methodologies, some features such as the occurrence of rRNA posttranscriptional modified bases are not fully addressed. However, conserved as it is, non-universal ribosomal features found in various reconstructions indicate that LCA's translation machinery was still evolving, thereby acquiring the domain specific features in the process. Although progenotes from the pre-LCA likely no longer exist recent results obtained by unraveling the early history of the ribosome and other genetic processes can provide insight to the nature of the pre-LCA world., (© 2024. The Author(s), under exclusive licence to Springer Science+Business Media, LLC, part of Springer Nature.)

Aims/hypothesis: Diabetic retinopathy is characterised by neuroinflammation that drives neuronal and vascular degenerative pathology, which in many individuals can lead to retinal ischaemia and neovascularisation. Infiltrating macrophages and activated retina-resident microglia have been implicated in the progression of diabetic retinopathy, although the distinct roles of these immune cells remain ill-defined. Our aim was to clarify the distinct roles of macrophages/microglia in the pathogenesis of proliferative ischaemic retinopathies., Methods: Murine oxygen-induced retinopathy is commonly used as a model of ischaemia-induced proliferative diabetic retinopathy (PDR). We evaluated the phenotype macrophages/microglia by immunostaining, quantitative real-time RT-PCR (qRT-PCR), flow cytometry and scRNA-seq analysis. In clinical imaging studies of diabetic retinopathy, we used optical coherence tomography (OCT) and OCT angiography., Results: Immunostaining, qRT-PCR and flow cytometry showed expression levels of M1-like macrophages/microglia markers (CD80, CD68 and nitric oxide synthase 2) and M2-like macrophages/microglia markers (CD206, CD163 and macrophage scavenger receptor 1) were upregulated in areas of retinal ischaemia and around neo-vessels, respectively. scRNA-seq analysis of the ischaemic retina revealed distinct ischaemia-related clusters of macrophages/microglia that express M1 markers as well as C-C chemokine receptor 2. Inhibition of Rho-kinase (ROCK) suppressed CCL2 expression and reduced CCR2-positive M1-like macrophages/microglia in areas of ischaemia. Furthermore, the area of retinal ischaemia was reduced by suppressing blood macrophage infiltration not only by ROCK inhibitor and monocyte chemoattractant protein-1 antibody but also by GdCl 3 . Clinical imaging studies of diabetic retinopathy using OCT indicated potential involvement of macrophages/microglia represented by hyperreflective foci in areas of reduced perfusion., Conclusions/interpretation: These results collectively indicated that heterotypic macrophages/microglia differentially contribute to retinal ischaemia and neovascularisation in retinal vascular diseases including diabetic retinopathy. This adds important new information that could provide a basis for a more targeted, cell-specific therapeutic approach to prevent progression to sight-threatening PDR., (© 2024. The Author(s), under exclusive licence to Springer-Verlag GmbH Germany, part of Springer Nature.)

Ribosome translocation catalyzed by elongation factor G (EF-G) is a critical step in protein synthesis where the ribosome typically moves along the mRNA by three nucleotides at each step. To investigate the mechanism of EF-G catalysis, it is essential to precisely resolve the ribosome motion at both ends of the mRNA, which, to our best knowledge, is only achieved with the magnetic-based force spectroscopy developed by our groups. Here, we introduce a novel multiplexed force spectroscopy technique that, for the first time, offers single-nucleotide resolution for multiple samples. This technique combines multiple acoustic force generators with the smallest atomic magnetometer designed for biological research. Utilizing this technique, we demonstrate that mutating EF-G at the GTP binding pocket results in the ribosome moving only two nucleotides on both ends of the mRNA, thereby compromising ribosome translocation. This finding suggests a direct link between GTP hydrolysis and ribosome translocation. Our results not only provide mechanistic insights into the role of GTP binding pocket but also illuminate how allosteric mutations can manipulate translocation. We anticipate broader applications of our technique in the ribosome field, leveraging its high efficiency and single-nucleotide resolution., (© 2024 Wiley-VCH GmbH.)

The last few years have seen a surge of interest from field ecologists and evolutionary biologists to study neoplasia and cancer in wildlife. This contributes to the One Health Approach, which investigates health issues at the intersection of people, wild and domestic animals, together with their changing environments. Nonetheless, the emerging field of wildlife cancer is currently constrained by methodological limitations in detecting cancer using non-invasive sampling. In addition, the suspected differential susceptibility and resistance of species to cancer often make the choice of a unique model species difficult for field biologists. Here, we provide an overview of the importance of pursuing the study of cancer in non-model organisms and we review the currently available methods to detect, measure and quantify cancer in the wild, as well as the methodological limitations to be overcome to develop novel approaches inspired by diagnostic techniques used in human medicine. The methodology we propose here will help understand and hopefully fight this major disease by generating general knowledge about cancer, variation in its rates, tumour-suppressor mechanisms across species as well as its link to life history and physiological characters. Moreover, this is expected to provide key information about cancer in wildlife, which is a top priority due to the accelerated anthropogenic change in the past decades that might favour cancer progression in wild populations., (© 2024 The Author(s). Journal of Animal Ecology published by John Wiley & Sons Ltd on behalf of British Ecological Society.)

Innate social behaviors like aggression are modulated by sex steroid hormones such as androgens and estrogens. However, we know little about how the same hormone regulates similar behaviors in both sexes. We investigated the role of androgenic signaling in the regulation of aggression in Astatotilapia burtoni, a social fish in which males and females perform similar aggressive behaviors. We used androgen receptor (AR) α knockout (KO) animals for this study since this gene was recently shown to be required for male-typical aggression and mating. Surprisingly, ARα KO females did not show deficits in aggression. We also determined that females lacking the other AR, ARβ, showed normal levels of aggression. Blocking both ARs pharmacologically confirmed that neither AR is necessary for aggression in females. However, ARα KO males showed clear deficits in attacks. Thus, in A. burtoni there appears to be a sexual dimorphism in the role of ARα in the control of aggression., Competing Interests: Declaration of competing interest None., (Copyright © 2024 Elsevier B.V. All rights reserved.)

Ferroptosis is a distinct form of regulated cell death that is predominantly driven by the build-up of intracellular iron and lipid peroxides. Ferroptosis suppression is widely accepted to contribute to the pathogenesis of several tumours including prostate cancer. Results from some studies reported that prostate cancer cells can be highly susceptible to ferroptosis inducers, providing potential for an interesting new avenue of therapeutic intervention for advanced prostate cancer. In this Perspective, we describe novel molecular underpinnings and metabolic drivers of ferroptosis, analyse the functions and mechanisms of ferroptosis in tumours, and highlight prostate cancer-specific susceptibilities to ferroptosis by connecting ferroptosis pathways to the distinctive metabolic reprogramming of prostate cancer cells. Leveraging these novel mechanistic insights could provide innovative therapeutic opportunities in which ferroptosis induction augments the efficacy of currently available prostate cancer treatment regimens, pending the elimination of major bottlenecks for the clinical translation of these treatment combinations, such as the development of clinical-grade inhibitors of the anti-ferroptotic enzymes as well as non-invasive biomarkers of ferroptosis. These biomarkers could be exploited for diagnostic imaging and treatment decision-making., (© 2024. Springer Nature Limited.)

Rheumatic diseases encompass a range of entities affecting the musculoskeletal system and connective tissue due to immune dysregulation. These entities include rheumatoid arthritis, systemic lupus erythematosus, and ankylosing spondylitis that present significant medical and social challenges by impacting individuals' quality of life and working capacity. In developing countries, where healthcare access is limited, the burden of these diseases is particularly severe. Analyzing the regional epidemiological characteristics of rheumatic diseases may enhance our understanding of risk factors and aid in developing targeted preventive measures. This study utilized data from the Republican Centre for Health Development in Kazakhstan from 2018 to 2021. The incidence of various rheumatic diseases was examined in the adult population of Shymkent, Kazakhstan, including rheumatoid arthritis, gout, osteoarthritis, systemic lupus erythematosus, dermatomyositis, scleroderma, and ankylosing spondylitis. Shymkent's total number of rheumatic disease cases rose from 52,617 in 2018 to 52,781 in 2021. Primary morbidity increased from 18,381 to 21,677 cases. Incidence rates for systemic lupus erythematosus, systemic scleroderma, and ankylosing spondylitis increased, while cases of rheumatoid arthritis and osteoarthritis showed fluctuation. Gender distribution analysis revealed that women were more frequently affected by rheumatoid arthritis and systemic lupus erythematosus whereas men were more prone to ankylosing spondylitis. The results underscore the need to tailor diagnostic and treatment approaches to account for age-and gender-specific differences in rheumatic diseases. The increased incidence of some diseases calls for new prevention and treatment strategies. This study highlights the significant burden of rheumatic diseases in Shymkent, Kazakhstan and emphasizes the importance of local epidemiological research in adapting medical practices to regional specifics., (© 2024. The Author(s), under exclusive licence to Springer-Verlag GmbH Germany, part of Springer Nature.)

Aims: The mechanisms regulating the cellular behaviour and cardiomyocyte organization during ventricular wall morphogenesis are poorly understood. Cardiomyocytes are surrounded by extracellular matrix (ECM) and interact with ECM via integrins. This study aims to determine whether and how β1 integrins regulate cardiomyocyte behaviour and organization during ventricular wall morphogenesis in the mouse., Methods and Results: We applied mRNA deep sequencing and immunostaining to determine the expression repertoires of α/β integrins and their ligands in the embryonic heart. Integrin β1 subunit (β1) and some of its ECM ligands are asymmetrically distributed and enriched in the luminal side of cardiomyocytes, and fibronectin surrounds cardiomyocytes, creating a network for them. Itgb1, which encodes the β1, was deleted via Nkx2.5Cre/+ to generate myocardial-specific Itgb1 knockout (B1KO) mice. B1KO hearts display an absence of a trabecular zone but a thicker compact zone. The levels of hyaluronic acid and versican, essential for trabecular initiation, were not significantly different between control and B1KO. Instead, fibronectin, a ligand of β1, was absent in the myocardium of B1KO hearts. Furthermore, B1KO cardiomyocytes display a random cellular orientation and fail to undergo perpendicular cell division, be organized properly, and establish the proper tissue architecture to form trabeculae. Mosaic clonal lineage tracing showed that Itgb1 regulates cardiomyocyte transmural migration and proliferation autonomously., Conclusion: β1 is asymmetrically localized in the cardiomyocytes, and some of its ECM ligands are enriched along the luminal side of the myocardium, and fibronectin surrounds cardiomyocytes. β1 integrins are required for cardiomyocytes to attach to the ECM network. This engagement provides structural support for cardiomyocytes to maintain shape, undergo perpendicular division, and establish cellular organization. Deletion of Itgb1 leads to loss of β1 and fibronectin and prevents cardiomyocytes from engaging the ECM network, resulting in failure to establish tissue architecture to form trabeculae., Competing Interests: Conflict of interest: none declared., (© The Author(s) 2024. Published by Oxford University Press on behalf of the European Society of Cardiology.)

A combination of life history traits and environmental conditions has been highlighted as the main drivers of avian breeding success. While drivers of breeding success are well known in some species, especially birds in northern, temperate regions; species in other parts of the world have received relatively little attention. In this study, we used a long-term dataset on breeding success of tropical plovers from south-west Madagascar to investigate whether nest survival changed over time and whether the drivers of nest survival were similar for multiple species breeding in the same arid habitat. In the 12-year period of 2009-2020, we monitored 2077 nests for three species with different breeding strategies: 1185 nests of Kittlitz's plovers ( Anarhynchus pecuarius ) with a flexible breeding strategy and uniparental care; and 565 nests of white-fronted plovers ( A. marginatus ) and 327 nests of Madagascar plovers ( A. thoracicus ) which both have biparental care. We found that nest survival was associated with a combination of clutch-size, age of nest and year among the three plover species. In addition, annual variation in climatic conditions associated with El Niño/La Niña events were included in the most supported survival models for Kittlitz's and white-fronted plovers, but the effects were not significant. Overall estimates of daily nest survival were similar for all three species: Kittlitz's plover: 0.950 ± 0.002 SE, Madagascar plover: 0.919 ± 0.007 SE, and white-fronted plover: 0.862 ± 0.047 SE. Estimates of nest success for the breeding season, based on increases in daily nest survival with the clutch age during the incubation periods (26 days for Kittlitz's plovers and 29 days for Madagascar and white-fronted plovers), were relatively low: Kittlitz's plover: 0.161 ± 0.056 SE, Madagascar plover: 0.287 ± 0.022 SE, and white-fronted plover: 0.228 ± 0.019 SE. All three species had a combination of factors affecting nest survival, both environmental and life history traits., Competing Interests: The authors have no conflicts of interest to declare., (© 2024 The Author(s). Ecology and Evolution published by John Wiley & Sons Ltd.)

PHD2 is essential in modulating HIF-1α levels upon oxygen fluctuations. Hypoxia, a hallmark of uterus, and HIF-1α have recently emerged as opposing regulators of mesendoderm specification, suggesting a role for PHD2 therein. We found that PHD2 expression initially covered the epiblast and gradually receded from the primitive streak, which was identical to hypoxia and exclusive to HIF-1α. The investigations performed in mESCs, embryoids, and mouse embryos together demonstrated that PHD2 negatively regulated mesendoderm specification. Single-cell RNA sequencing revealed that PHD2 governed the transition from epiblast to mesendoderm. The downstream effect of PHD2 relied on the HIF-1α regulated Wnt/β-catenin pathway, while it was regulated upstream by miR-429. In summary, our research highlights PHD2's essential role in mesendoderm specification and its interactions with hypoxia and HIF-1α., (© 2024. The Author(s).)

During breeding when testosterone concentrations are high, male songbirds that are open-ended vocal learners like canaries (Serinus canaria) tend to produce a stable, stereotyped song that facilitates mate attraction or territory defense. Outside breeding contexts, song becomes more variable. The neuroendocrine mechanisms controlling this vocal variability across seasons are not entirely clear. We tested whether androgen signaling within the lateral magnocellular nucleus of the anterior nidopallium (LMAN), a cortical-like brain region of the vocal control system known as a vocal variability generator, plays a role in seasonal vocal variability. We first characterized song in birds housed alone on a short day (SD) photoperiod, which simulates non-breeding conditions. Then, cannulae filled with the androgen receptor (AR) blocker flutamide or left empty as control were implanted bilaterally in LMAN. Birds were then transferred to long days (LD) to simulate the breeding season and song was analyzed again. Blocking AR in LMAN increased acoustic variability of song and the acoustic variability of syllables. However, blocking AR in LMAN did not impact the variability of syllable usage nor their sequencing in LD birds, song features that are controlled by androgen signaling in a somatosensory brain region of the vocal control system called HVC. These findings highlight the multifactorial, non-redundant actions of steroid hormones in controlling complex social behaviors such as birdsong. They also support the hypothesis that LMAN is a key brain area for the effects of testosterone on song plasticity both seasonally in adults and during the song crystallization process at sexual maturity., (Copyright © 2024 Elsevier Inc. All rights reserved.)

Inflammatory rheumatic diseases (IRDs) refer to a range of persistent disorders that have a major influence on several physiological systems. Although there is much evidence connecting IRDs to sexual dysfunction and fertility problems, research specifically focusing on male infertility in relation to these diseases is sparse. This review addresses the complicated connection between IRDs and male infertility, emphasising the physiological, psychological, and pharmacological aspects that influence reproductive health outcomes in men with rheumatic conditions. We explore the effects of IRDs and their treatments on many facets of male reproductive well-being, encompassing sexual functionality, semen characteristics, and hormonal balance. Additionally, we present a comprehensive analysis of the present knowledge on the impact of several categories of anti-rheumatic drugs on male reproductive function. Although there is an increasing awareness of the need of addressing reproductive concerns in individuals IRDs, there is a noticeable lack of research especially dedicated to male infertility. Moving forward, more comprehensive research is needed to determine the prevalence, risk factors, and mechanisms driving reproductive difficulties in males with IRDs. We can better assist the reproductive health requirements of male IRD patients by expanding our understanding of male infertility in the setting of rheumatic disorders and implementing holistic methods to care., (© 2024. The Author(s).)

Animals encounter diverse microbial communities throughout their lifetime, which exert varying selection pressures. Antimicrobial peptides (AMPs), which lyse or inhibit microbial growth, are a first line of defense against some of these microbes. Here we examine how developmental variation in microbial exposure has affected the evolution of expression and amino acid sequences of Defensins (an ancient class of AMPs) in the house fly ( Musca domestica ). The house fly is a well-suited model for this work because it trophically associates with varying microbial communities throughout its life history and its genome contains expanded families of AMPs, including Defensins. We identified two subsets of house fly Defensins: one expressed in larvae or pupae, and the other expressed in adults. The amino acid sequences of these two Defensin subsets form distinct monophyletic clades, and they are located in separate gene clusters in the genome. The adult-expressed Defensins evolve faster than larval/pupal Defensins, consistent with different selection pressures across developmental stages. Our results therefore suggest that varied microbial communities encountered across life history can shape the evolutionary trajectories of immune genes., Competing Interests: The authors declare there are no competing interests.

Rheumatoid arthritis (RA) is a common chronic autoimmune disease characterized by symmetrical polyarthritis, joint pain, and morning stiffness. It significantly impairs physical condition and increases the risk of functional disability. While conventional treatments include drug therapy, many patients continue to experience symptoms and seek alternative therapies to improve their condition. This article describes two clinical cases of RA patients treated with a comprehensive rehabilitation program, including moderate-intensity walking, yoga, and nutritional therapy. The study aimed to evaluate this approach's effectiveness in improving the patients' functional capacity and quality of life. The first patient (50 year-old female) noted a significant reduction in the number of painful joints (by 14) and swollen joints (by 12) after a three-month rehabilitation course. The visual analog scale (VAS) pain level decreased from 80 mm to 50 mm, and the duration of morning stiffness decreased from several hours to 80 min. The second patient (45 year-old female) also showed improvement: painful joints decreased from 13 to 2, and swollen joints from 7 to 1. VAS pain level decreased from 80 mm to 40 mm, and morning stiffness decreased by 50 min. Both patients reported an average reduction in excess weight by 1.65 kg/m², along with improvements in general well-being and mood. The results confirm that a comprehensive rehabilitation approach, including physical activity, yoga, and diet therapy, significantly improves the condition of RA patients. This approach helps reduce pain, decrease the number of inflamed joints, and improve overall functionality. Further studies with a larger sample are needed to determine the optimal rehabilitation strategies and the most impactful interventions., (© 2024. The Author(s), under exclusive licence to Springer-Verlag GmbH Germany, part of Springer Nature.)

Introduction: Cardiovascular disease (CVD) presents a significant challenge in rheumatoid arthritis (RA), a systemic chronic ailment affecting the joints and causing systemic inflammation. Effective RA management, including pharmacological and non-pharmacological interventions, is crucial for mitigating cardiac risk. Pharmacotherapy, though effective, can have adverse effects, leading many patients to seek complementary therapies. This study investigates the impact of physical medicine and rehabilitation on RA management in patients with cardiovascular disease, analyzing clinical data to assess the efficacy of integrated therapeutic approaches., Methods: This retrospective monocentric study draws upon data from patient records at the Rheumatology Department of the Regional Clinical Hospital of Shymkent, Kazakhstan, spanning 2019 to 2022. Data collected included demographic information, diagnoses, comorbidities, medical anamneses, lab results, and treatment regimens, including physical medicine and rehabilitation interventions. Data were summarized in Microsoft Excel. Statistical analysis was performed using IBM SPSS Statistics (version 26.0)., Results: An analysis of 350 patients with RA identified 143 cases of concomitant CVD, with arterial hypertension being the most common cardiovascular disease. The prevalence of CVD among patients with RA was 40%, with a mean age of 58 years, peaking between 50 and 65 years. The majority of patients were women. A strong association was found between increased RA activity and elevated cardiovascular risk. Despite the widespread use of glucocorticosteroid therapy, rehabilitation coverage remained limited. A significant proportion of patients had elevated cholesterol and C-reactive protein levels, while those who engaged in physical therapy and rehabilitation had lower cholesterol levels. Comparative analysis of yoga integration into rehabilitation programs for patients with RA, alongside other modalities (kinesiotherapy, balneotherapy, and pilates), showed that yoga participants exhibited lower pain levels, reduced morning stiffness duration, and lower mean DAS-28 scores compared to those using alternative rehabilitation methods., Conclusion: Integrating physical medicine and rehabilitation, particularly yoga, with pharmacological treatments appears promising for improving patient outcomes. Yoga has demonstrated benefits in reducing pain, morning stiffness, and disease activity. Continued research is essential to refine these approaches and enhance RA and CVD management in patients., (© 2024. The Author(s), under exclusive licence to Springer-Verlag GmbH Germany, part of Springer Nature.)

The detection of nucleic acids that are present in atypical conformations is a crucial trigger of the innate immune response. Human Z-DNA binding protein 1 (ZBP1) is a pattern recognition receptor that harbors two Zα domains that recognize Z-DNA and Z-RNA. ZBP1 detects this alternate nucleic acid conformation as foreign, and upon stabilization of these substrates, it triggers activation of an immune response. Here, we present the backbone chemical shift assignment of a construct encompassing the Zα1 and Zα2 domains as well as the interconnecting linker of ZBP1. These assignments can be directly transferred to the isolated Zα1 and Zα2 domains, thereby demonstrating that these domains maintain virtually identical structures in the tandem context., (© 2024. The Author(s), under exclusive licence to Springer Nature B.V.)