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Macroecologists traditionally emphasized the role of environmental variables for predicting species distribution and abundance at large scale. While biotic factors have been increasingly recognized as important at macroecological scales, producing valuable biotic variables remains challenging and rarely tested. Capitalizing on the wealth of population density estimates available for African savannah ungulates, here we modeled species average population density at 100 × 100 km as a function of both environmental variables and proxies of biotic interactions (competition and predation) and estimated their relative contribution. We fitted a linear mixed effect model on 1043 population density estimates for 63 species of ungulates using Bayesian inference and estimated the percentage of total variance explained by environmental, anthropogenic, and biotic interactions variables. Environmental and anthropogenic variables were the main drivers of ungulate population density, with NDVI, Distance to permanent water bodies and Human population density showing the highest contribution to the variance. Nonetheless, biotic interactions altogether contributed to a quarter of the variance explained, with predation and competition having a negative effect on species density. Despite the limitations of modelling biotic interactions in macroecological studies, proxies of biotic interactions can enhance our understanding of biological patterns at broad spatial scales, uncovering novel predictors as well as enhancing the predictive power of large-scale models. [ABSTRACT FROM AUTHOR]

Background: The HeartLogic algorithm (Boston Scientific, St Paul, MN) integrates data from implantable cardioverter-defibrillator (ICD) sensors to predict heart failure (HF) decompensation: first (S1) and third (S3) heart sounds, intrathoracic impedance, respiration rate, ratio of respiration rate to tidal volume (RSBI), and night heart rate., Objective: This study assessed the relative changes in ICD sensors at the onset of HeartLogic alerts, their association with patient characteristics, and outcomes., Methods: The study included 568 patients with HF carrying ICDs (CRT-D, n = 410) across 26 centers, with a median follow-up of 26 months. HeartLogic alerts triggered patient contact and potential treatment., Results: A total of 1200 HeartLogic alerts were recorded in 370 patients. The sensor with the highest change at the alert's onset was S3 in 27% of alerts, followed by S3/S1 (25%). Patients with atrial fibrillation (AF) and chronic kidney disease (CKD) at implantation had higher prevalence of alerts (AF, 84% vs no AF, 58%; CKD, 72% vs no CKD, 59%; P < .05) and rate (AF, 1.51 per patient-year vs no AF, 0.88 per patient-year; CKD, 1.30 per patient-year vs no CKD, 0.89 per patient-year; P < .05). During follow-up, 247 patients experienced more than 1 alert; in 85%, the sensor with the highest change varied between successive alerts. Of the 88 (7%) alerts associated with HF hospitalization or death, respiration rate or RSBI (11%, P = .007 vs S3/S1) and night heart rate (11%, P = .031 vs S3/S1) were more commonly the sensors showing the highest change. Clinical events were more common with the first alert (12.6%) than subsequent alerts (5.2%, P < .001)., Conclusion: HeartLogic alerts are mostly triggered by changes in heart sounds, but clinical events are more linked to respiration rate, RSBI, and night heart rate. Recurrent alerts often involve different sensors, indicating diverse mechanisms of HF progression., Competing Interests: Disclosures Dr Dello Russo is consultant for Abbott, Biosense Webster, and Boston Scientific. Dr Santini is consultant for Abbott, Boston Scientific, Medtronic, and Biotronik and is a speaker for Medtronic, Boston Scientific, Abbott, Microport, and Biotronik. Dr Bertini is a consultant for Boston Scientific and Microport; speaker and tutor in training courses for Boston Scientific, Microport, Medtronic, Abbott, Biotronik, Pfizer, Bayer, Daiichi-Sankyo, and Boehringer Ingelheim. Dr Casella has received speaker honoraria from Biosense Webster. Dr Averina, Dr Campari, and Dr Valsecchi are employees of Boston Scientific. The remaining authors have no conflicts of interest to disclose., (Copyright © 2024 Heart Rhythm Society. Published by Elsevier Inc. All rights reserved.)

Meningococcal glycoconjugate vaccines sourced from capsular polysaccharides (CPSs) of pathogenic Neisseria meningitidis strains are well-established measures to prevent meningococcal disease. However, the exact structural factors responsible for antibody recognition are not known. CPSs of Neisseria meningitidis serogroups Y and W differ by a single stereochemical center, yet they evoke specific immune responses. Herein, we developed specific monoclonal antibodies (mAbs) targeting serogroups C, Y, and W and evaluated their ability to kill bacteria. We then used these mAbs to dissect structural elements responsible for carbohydrate-protein interactions. First, Men oligosaccharides were screened against the mAbs using ELISA to select putative lengths representing the minimal antigenic determinant. Next, molecular interaction features between the mAbs and serogroup-specific sugar fragments were elucidated using STD-NMR. Moreover, X-ray diffraction data with the anti-MenW CPS mAb enabled the elucidation of the sugar-antibody binding mode. Our findings revealed common traits in the epitopes of all three sialylated serogroups. The minimal binding epitopes typically comprise five to six repeating units. Moreover, the O-acetylation of the neuraminic acid moieties was fundamental for mAb binding. These insights hold promise for the rational design of optimized meningococcal oligosaccharides, opening new avenues for novel production methods, including chemical or enzymatic approaches., Competing Interests: Declaration of competing interest LS, MRR and RA are employee of GSK. GPP was a PhD fellow of MEDRI and performed a secondment in GSK during his doctorate. Menjugate, Menveo, Menitorix, Menhibrix are registered trademarks from GSK Vaccines; Menactra is a registered trademark from Sanofi Pasteur; Nimenrix is a registered trademark from Pfizer; NeisVac is a registerd trademark from North American Vaccine Inc.- Baxter Bioscience., (Copyright © 2024 The Authors. Published by Elsevier Ltd.. All rights reserved.)

Background: No data regarding subcutaneous-implantable cardioverter defibrillator (S-ICD) technology in patients actively engaging in sports activities are available., Objective: This study aims to compare S-ICD performance between athletes and nonathletes., Methods: The primary outcome of the study was the comparison of overall device-related complications between athletes and nonathletes. Appropriate shocks, inappropriate shocks, and individual device-related complications were secondary outcomes., Results: A total of 1493 patients were extracted from the International Subcutaneous Implantable Cardioverter Defibrillator Registry (iSUSI) registry, of whom 152 (10.2%) were athletes, mostly engaging in dynamic sports (54.2%). Brugada syndrome, myocarditis, and arrhythmogenic right ventricular cardiomyopathy (ARVC) were more common in athletes (11.2% vs 3.3%, P < .001; 19.1% vs 9.0%, P < .001; 8.6% vs 2.8%, P < .001, respectively). During a median follow-up time of 25.5 (12.0-41.2) months, athletes were more likely to experience appropriate shocks (yearly rate: 7.2 [4.9-10.7] % vs 4.3 [3.6-5.1] %, P = .028), occurring more frequently during exercise (3.9% vs 0.6%, P < .001). This finding lost significance when adjusting for confounders (adjusted hazard ratio [aHR] 1.440 [0.909-2.281], P = .120). No differences were found in overall device-related complications (yearly rate: 3.3% vs 3.4%, P = .448) and inappropriate shocks (yearly rate: 5.3% vs 3.7%, P = 0.111). Myopotential oversensing (4.0% vs 1.3%, P = .011) was more common in athletes, as were lead infections (3.3% vs 0.9%, P =.008), with the latter clustering in the early postimplantation period., Conclusion: The S-ICD is a valid therapeutic option for preventing sudden cardiac death in athletes. Sports practice was not associated with an increased risk of complications or inappropriate shocks, although athletes are exposed to a higher risk of S-ICD infections in the early postoperative period., Competing Interests: Disclosures Dr Breitenstein has received consultant/speaker fees from Boston Scientific. Dr Martinek has received speaker`s honoraria from Boston Scientific. Dr Kaiser has received proctor fees from Boston Scientific. Dr Tilz consults for and has received speaker`s honoraria from Boston Scientific. Dr Tondo is a member of Boston Scientific advisory board. The other authors have no conflicts of interest to disclose., (Copyright © 2024 Heart Rhythm Society. Published by Elsevier Inc. All rights reserved.)

Naïve pluripotency is sustained by a self-reinforcing gene regulatory network (GRN) comprising core and naïve pluripotency-specific transcription factors (TFs). Upon exiting naïve pluripotency, embryonic stem cells (ESCs) transition through a formative post-implantation-like pluripotent state, where they acquire competence for lineage choice. However, the mechanisms underlying disengagement from the naïve GRN and initiation of the formative GRN are unclear. Here, we demonstrate that phosphorylated AKT acts as a gatekeeper that prevents nuclear localisation of FoxO TFs in naïve ESCs. PTEN-mediated reduction of AKT activity upon exit from naïve pluripotency allows nuclear entry of FoxO TFs, enforcing a cell fate transition by binding and activating formative pluripotency-specific enhancers. Indeed, FoxO TFs are necessary and sufficient for the activation of the formative pluripotency-specific GRN. Our work uncovers a pivotal role for FoxO TFs in establishing formative post-implantation pluripotency, a critical early embryonic cell fate transition., (© 2024. The Author(s).)

Background: The programing of subcutaneous implantable cardioverter-defibrillators (S-ICD) in clinical practice has been little studied, as the activation status of the SMART Pass filter, which was implemented to reduce inappropriate shocks., Purpose: We assessed device programing during follow-up and the rate of detected arrhythmias in consecutive S-ICD recipients., Methods: We analyzed data from 670 S-ICD patients followed on the remote network at 17 Italian centers for a median of 31 months (25th-75th percentile: 16-51). The enhanced SMART Pass version, introduced in October 2022, was expected to reduce the unintentional deactivation rate., Results: At the latest remote data transmission, the median conditional zone cut-off was set to 210 bpm (25th-75th percentile: 200-220), the shock zone cutoff was 250 bpm (25th-75th percentile: 240-250), and the SMART Pass was enabled in 586 (87%) patients. During follow-up, 194 automatic deactivation events were reported in 118 (18%) patients. Shocks were delivered in 129 (19%) patients, and untreated arrhythmias were recorded in 136 (20%) patients. The rate of shocks was lower when SMART Pass was enabled -0.12/patient-year (95% CI: 0.10-0.14) versus 0.20 (95% CI: 0.15-0.26) (p = .002), as it was the rate of untreated arrhythmias -0.12/patient-year (95% CI: 0.11-0.14) versus 0.23 (95% CI: 0.18-0.30) (p = .001). The enhanced SMART Pass version was associated with a lower rate of deactivations -0.04/patient-year (95% CI: 0.02-0.05) versus 0.14 (95% CI: 0.12-0.16) (p < .001), and with a reduction in treated and untreated arrhythmias (Incidence rate ratios: 0.40 (95% CI: 0.28-0.53) and 0.40 (95% CI: 0.30-0.55), respectively (p < .001))., Conclusions: Centers tend to program devices to detect high ventricular rates for arrhythmia detection, to minimize inappropriate shock occurrences. SMART Pass activation is associated with lower rates of detected and treated arrhythmias. The enhanced SMART Pass version seems associated with a lower deactivation rate and with a further decrease in treated arrhythmias., (© 2024 Wiley Periodicals LLC.)

The aim of this study was to determine whether brushing rams before and during electroejaculation (EE) reduces their stress response and improves the characteristics of the ejaculate. A single person brushed each ram for 5 min daily, for 15 days, in an individual pen. Semen was collected from five rams brushed before and during EE by the same brusher, while the other five were electroejaculated without being brushed. The treatments were exchanged three days later, so semen was collected from all the rams with both treatments. Brushing increased mass motility (P = 0.05), and curvilinear (P = 0.001), linear (P = 0.02), and average path (P = 0.01) velocities of sperm, as well as the average amplitude of lateral displacement of the sperm head (P = 0.05), and tended to increase sperm concentration (P = 0.09). Brushing tended to reduce the cortisol concentration (P = 0.06) and the duration of head movements when 2 V pulse series V was applied (P = 0.1). Brushing increased creatine kinase concentration (P = 0.04) and tended to increase rectal (P = 0.06) and maximum eye surface temperatures (P = 0.1), total time, and number of electrical pulses administered (P = 0.07 for both variables), as well as the sum of pulses per voltage applied during EE (P = 0.06). In rams accustomed to being brushed by the same person, brushing them before and during EE improved semen quality, with slight changes in the stress responses., Competing Interests: Declaration of Competing Interest Authors have no conflict of interest, (Copyright © 2024 Elsevier B.V. All rights reserved.)

An 88-year-old patient underwent pacemaker generator replacement. Shortly after the replacement, the pacemaker pocket became swollen and, assuming a hematoma, underwent percutaneous drainage. However, the swelling was due to an aggressive lymphoma located in the pocket. This is the first described case of T-cell lymphoma in a pacemaker pocket., Competing Interests: Dr Santini has been a consultant for Boston Scientific, Abbott, and Medtronic; and has received speaker fees from Zoll. All other authors have reported that they have no relationships relevant to the contents of this paper to disclose., (© 2024 The Authors.)

Assessing the extinction risk of species based on the International Union for Conservation of Nature (IUCN) Red List (RL) is key to guiding conservation policies and reducing biodiversity loss. This process is resource demanding, however, and requires continuous updating, which becomes increasingly difficult as new species are added to the RL. Automatic methods, such as comparative analyses used to predict species RL category, can be an efficient alternative to keep assessments up to date. Using amphibians as a study group, we predicted which species are more likely to change their RL category and thus should be prioritized for reassessment. We used species biological traits, environmental variables, and proxies of climate and land-use change as predictors of RL category. We produced an ensemble prediction of IUCN RL category for each species by combining 4 different model algorithms: cumulative link models, phylogenetic generalized least squares, random forests, and neural networks. By comparing RL categories with the ensemble prediction and accounting for uncertainty among model algorithms, we identified species that should be prioritized for future reassessment based on the mismatch between predicted and observed values. The most important predicting variables across models were species' range size and spatial configuration of the range, biological traits, climate change, and land-use change. We compared our proposed prioritization index and the predicted RL changes with independent IUCN RL reassessments and found high performance of both the prioritization and the predicted directionality of changes in RL categories. Ensemble modeling of RL category is a promising tool for prioritizing species for reassessment while accounting for models' uncertainty. This approach is broadly applicable to all taxa on the IUCN RL and to regional and national assessments and may improve allocation of the limited human and economic resources available to maintain an up-to-date IUCN RL., (© 2024 The Author(s). Conservation Biology published by Wiley Periodicals LLC on behalf of Society for Conservation Biology.)

Thousands of disease cases and hundreds of deaths occur globally each year due to invasive meningococcal disease. Neisseria meningitidis serogroup B (MenB) is the leading cause of such disease in developed countries. Two vaccines, 4CMenB and MenB-fHbp, that protect against MenB are available and include one or two forms respectively of factor H binding protein (fHbp), a key protective antigen. Studies of circulating meningococci have identified over 1380 different fHbp amino acid sequences, which form three immunologically distinct clusters, termed variants 1, 2, and 3. Neither of the current vaccines contains a variant 2 antigen, which is less well characterized than fHbp variants 1 and 3. We characterized the interaction of fHbp variant 2 with humAb 1B1 using biochemical methods and live meningococcal assays. Further, we determined the crystal structure of the complex at 2.4 Å resolution, clearly revealing the epitope and providing the first detailed report of an antibody with distinct specificity for fHbp variant 2. Extensive mutagenesis and binding studies elucidated key hotspots in the interface. This combination of structural and functional studies provides a molecular explanation for the bactericidal potency and specificity of humAb 1B1 for fHbp variant 2. Our studies, focused on fHbp variant 2, expand the understanding of this previously under characterized group of the vast family of variants of fHbp, a virulence factor present on all meningococci. Moreover, the definition of a protective conformational epitope on fHbp variant 2 may support the design and development of novel variant 2-containing MenB vaccines affording greater breadth of protection., Competing Interests: All authors were employees of the GSK group of companies at the time of the study, with the exception of FB, who held a PhD studenship at the University of Florence, Italy. The authors DV and MJB are named inventors on patent applications related to fHbp polypeptides. MJB, DM report ownership of GSK shares., (©2024 The Authors FASEB BioAdvances published by The Federation of American Societies for Experimental Biology.)

The directed differentiation of pluripotent stem cells (PSCs) from panels of genetically diverse individuals is emerging as a powerful experimental system for characterizing the impact of natural genetic variation on developing cell types and tissues. Here, we establish new PSC lines and experimental approaches for modeling embryonic development in a genetically diverse, outbred mouse stock (Diversity Outbred mice). We show that a range of inbred and outbred PSC lines can be stably maintained in the primed pluripotent state (epiblast stem cells -- EpiSCs) and establish the contribution of genetic variation to phenotypic differences in gene regulation and directed differentiation. Using pooled in vitro fertilization, we generate and characterize a genetic reference panel of Diversity Outbred PSCs (n = 230). Finally, we demonstrate the feasibility of pooled culture of Diversity Outbred EpiSCs as "cell villages", which can facilitate the differentiation of large numbers of EpiSC lines for forward genetic screens. These data can complement and inform similar efforts within the stem cell biology and human genetics communities to model the impact of natural genetic variation on phenotypic variation and disease-risk., Competing Interests: DECLARATION OF INTERESTS The authors declare no competing interests.

Measuring and tracking biodiversity from local to global scales is challenging due to its multifaceted nature and the range of metrics used to describe spatial and temporal patterns. Abundance can be used to describe how a population changes across space and time, but it can be measured in different ways, with consequences for the interpretation and communication of spatiotemporal patterns. We differentiate between relative and absolute abundance, and discuss the advantages and disadvantages of each for biodiversity monitoring, conservation, and ecological research. We highlight when absolute abundance can be advantageous and should be prioritized in biodiversity monitoring and research, and conclude by providing avenues for future research directions to better assess the necessity of absolute abundance in biodiversity monitoring., Competing Interests: Declaration of interests The authors have no interests to declare., (Copyright © 2024 Elsevier Ltd. All rights reserved.)

The International Union for Conservation of Nature (IUCN) Red List is a central tool for extinction risk monitoring and influences global biodiversity policy and action. But, to be effective, it is crucial that it consistently accounts for each driver of extinction. Climate change is rapidly becoming a key extinction driver, but consideration of climate change information remains challenging for the IUCN. Several methods can be used to predict species' future decline, but they often fail to provide estimates of the symptoms of endangerment used by IUCN. We devised a standardized method to measure climate change impact in terms of change in habitat quality to inform criterion A3 on future population reduction. Using terrestrial nonvolant tetrapods as a case study, we measured this impact as the difference between the current and the future species climatic niche, defined based on current and future bioclimatic variables under alternative model algorithms, dispersal scenarios, emission scenarios, and climate models. Our models identified 171 species (13% out of those analyzed) for which their current red-list category could worsen under criterion A3 if they cannot disperse beyond their current range in the future. Categories for 14 species (1.5%) could worsen if maximum dispersal is possible. Although ours is a simulation exercise and not a formal red-list assessment, our results suggest that considering climate change impacts may reduce misclassification and strengthen consistency and comprehensiveness of IUCN Red List assessments., (© 2024 The Authors. Conservation Biology published by Wiley Periodicals LLC on behalf of Society for Conservation Biology.)

Purpose: Parotid pleomorphic adenomas present a risk of recurrence, higher when the tumour is a hypocellular subtype. The aim of the study was to determine whether it is possible to characterize this histological subtype with diffusion and perfusion sequences of the preoperative MRI., Methods: This retrospective study included 97 patients operated between 2010 and 2020. Histologic slides review was performed to classify tumours into three histologic subtypes: hypocellular, classical and hypercellular. Univariate and multivariate analyses studied the correlation between histology and diffusion and perfusion MRI parameters obtained with OleaSphere® software., Results: The hypocellular subtype had higher apparent diffusion coefficient values than the other two subtypes: 2.13 ± 0.23, 1.83 ± 0.42, and 1.61 ± 0.4 × 10 -3  mm 2 /s for hypocellular, classical and hypercellular subtype respectively (p < 0.0001). Multivariate analysis showed that an ADC mean > 1.88 × 10 -3  mm 2 /s was suggestive of a hypocellular pleomorphic adenoma in 79% of the cases, with a specificity and PPV of 94 and 96% (p < 0.001), respectively., Conclusion: The histological subtype of a pleomorphic adenoma can be predicted preoperatively with ADC values. A prospective and multicentric study on a larger cohort is needed to confirm our results., (© 2024. The Author(s), under exclusive licence to Springer-Verlag GmbH Germany, part of Springer Nature.)

Choosing Wisely is an initiative by the American Board of Internal Medicine (ABIM) and ABIM Foundation to deter unnecessary medical treatments and procedures. Faced with the burden of modern technologies and treatments, it is crucial to identify practices lacking value in daily care. The Latin American and Caribbean Society (SLACOM), comprising cancer control experts, deems it vital to tailor this initiative for enhancing cancer care in the region. Through a modified DELPHI methodology involving two rounds of electronic questionnaires and a hybrid meeting to discuss key points of contention, ten essential recommendations were identified and prioritised to avoid harmful oncology procedures in our region. These consensus-based recommendations, contextualised for Latin America, have been compiled and shared to benefit patients. The Scientific Committee, consisting of prominent oncologists and health experts, collaborates remotely to drive this project forward., Competing Interests: The authors declare that they have no conflicts of interest., (© the authors; licensee ecancermedicalscience.)

Background: Transoral robotic surgery (TORS) opens new perspectives. We evaluated the outcomes for patients having undergone TORS after previous radiotherapy., Methods: A retrospective multicenter study (n = 138) in a previously irradiated area between 2009 and 2020. Survival was assessed with the Kaplan-Meier method. Prognostic factors were evaluated using a chi-squared test, Fisher's test, or Wilcoxon's test., Results: The median length of hospital stay was 12.5 days. Bleeding was the most frequent postoperative complication (15.2%, n = 22). Prophylactic vessel ligation did not significantly decrease bleeding. Complications were significantly lower for Tis, T1, and N0 tumors. 91.6% (n = 120) of the patients with a perioperative tracheotomy could be decannulated. Larynx was functional for 65.94% of the patients. The median length of follow-up was 26 months. The 5-year overall and relapse-free survival rates were respectively 59.9% and 43.4%., Conclusion: Oncological and functional results confirmed the value of TORS as a treatment in previously irradiated area., (© 2024 The Authors. Cancer Medicine published by John Wiley & Sons Ltd.)

We explored the results of two tests of the novel HeartInsight algorithm for heart failure (HF) prediction, reconstructing trends from historical cases. Results suggest potential extension of HeartInsight to implantable cardioverter defibrillators patients without history of HF and illustrate the importance of the baseline clinical profile in enhancing algorithm specificity., Competing Interests: Luca Santini served as consultant to Abbott, Medtronic, Boston Scientific, and Dompè, and received speaking honoraria for Medtronic, Boston Scientific, Abbott, Microport, and Boeheringher. Alessio Ferrara, Paola Napoli, and Daniele Giacopelli are employees of Biotronik Italia S.p.a. The remaining authors have nothing to disclose., (© 2024 The Authors. Journal of Arrhythmia published by John Wiley & Sons Australia, Ltd on behalf of Japanese Heart Rhythm Society.)

Background: Achieving a high biventricular pacing percentage (BiV%) is crucial for optimizing outcomes in cardiac resynchronization therapy (CRT). The HeartLogic index, a multiparametric heart failure (HF) risk score, incorporates implantable cardioverter-defibrillator (ICD)-measured variables and has demonstrated its predictive ability for impending HF decompensation., Objective: This study aimed to investigate the relationship between daily BiV% in CRT ICD patients and their HF status, assessed using the HeartLogic algorithm., Methods: The HeartLogic algorithm was activated in 306 patients across 26 centers, with a median follow-up of 26 months (25th-75th percentile: 15-37)., Results: During the follow-up period, 619 HeartLogic alerts were recorded in 186 patients. Overall, daily values associated with the best clinical status (highest first heart sound, intrathoracic impedance, patient activity; lowest combined index, third heart sound, respiration rate, night heart rate) were associated with a BiV% exceeding 99%. We identified 455 instances of BiV% dropping below 98% after consistent pacing periods. Longer episodes of reduced BiV% (hazard ratio: 2.68; 95% CI: 1.02-9.72; P = .045) and lower BiV% (hazard ratio: 3.97; 95% CI: 1.74-9.06; P =.001) were linked to a higher risk of HeartLogic alerts. BiV% drops exceeding 7 days predicted alerts with 90% sensitivity (95% CI [74%-98%]) and 55% specificity (95% CI [51%-60%]), while BiV% ≤96% predicted alerts with 74% sensitivity (95% CI [55%-88%]) and 81% specificity (95% CI [77%-85%])., Conclusion: A clear correlation was observed between reduced daily BiV% and worsening clinical conditions, as indicated by the HeartLogic index. Importantly, even minor reductions in pacing percentage and duration were associated with an increased risk of HF alerts., (© 2024 Heart Rhythm Society.)

T-tubules (TT) form a complex network of sarcolemmal membrane invaginations, essential for well-co-ordinated excitation-contraction coupling (ECC) and thus homogeneous mechanical activation of cardiomyocytes. ECC is initiated by rapid depolarization of the sarcolemmal membrane. Whether TT membrane depolarization is active (local generation of action potentials; AP) or passive (following depolarization of the outer cell surface sarcolemma; SS) has not been experimentally validated in cardiomyocytes. Based on the assessment of ion flux pathways needed for AP generation, we hypothesize that TT are excitable. We therefore explored TT excitability experimentally, using an all-optical approach to stimulate and record trans-membrane potential changes in TT that were structurally disconnected, and hence electrically insulated, from the SS membrane by transient osmotic shock. Our results establish that cardiomyocyte TT can generate AP. These AP show electrical features that differ substantially from those observed in SS, consistent with differences in the density of ion channels and transporters in the two different membrane domains. We propose that TT-generated AP represent a safety mechanism for TT AP propagation and ECC, which may be particularly relevant in pathophysiological settings where morpho-functional changes reduce the electrical connectivity between SS and TT membranes. KEY POINTS: Cardiomyocytes are characterized by a complex network of membrane invaginations (the T-tubular system) that propagate action potentials to the core of the cell, causing uniform excitation-contraction coupling across the cell. In the present study, we investigated whether the T-tubular system is able to generate action potentials autonomously, rather than following depolarization of the outer cell surface sarcolemma. For this purpose, we developed a fully optical platform to probe and manipulate the electrical dynamics of subcellular membrane domains. Our findings demonstrate that T-tubules are intrinsically excitable, revealing distinct characteristics of self-generated T-tubular action potentials. This active electrical capability would protect cells from voltage drops potentially occurring within the T-tubular network., (© 2024 The Authors. The Journal of Physiology published by John Wiley & Sons Ltd on behalf of The Physiological Society.)

Comparative extinction risk analysis-which predicts species extinction risk from correlation with traits or geographical characteristics-has gained research attention as a promising tool to support extinction risk assessment in the IUCN Red List of Threatened Species. However, its uptake has been very limited so far, possibly because existing models only predict a species' Red List category, without indicating which Red List criteria may be triggered. This prevents such approaches to be integrated into Red List assessments. We overcome this implementation gap by developing models that predict the probability of species meeting individual Red List criteria. Using data on the world's birds, we evaluated the predictive performance of our criterion-specific models and compared it with the typical criterion-blind modelling approach. We compiled data on biological traits (e.g. range size, clutch size) and external drivers (e.g. change in canopy cover) often associated with extinction risk. For each specific criterion, we modelled the relationship between extinction risk predictors and species' Red List category under that criterion using ordinal regression models. We found criterion-specific models were better at identifying threatened species compared to a criterion-blind model (higher sensitivity), but less good at identifying not threatened species (lower specificity). As expected, different covariates were important for predicting extinction risk under different criteria. Change in annual temperature was important for criteria related to population trends, while high forest dependency was important for criteria related to restricted area of occupancy or small population size. Our criteria-specific method can support Red List assessors by producing outputs that identify species likely to meet specific criteria, and which are the most important predictors. These species can then be prioritised for re-evaluation. We expect this new approach to increase the uptake of extinction risk models in Red List assessments, bridging a long-standing research-implementation gap., (© 2024 The Authors. Global Change Biology published by John Wiley & Sons Ltd.)