Sterol-Rich Membrane Domains Define Fission Yeast Cell Polarity.

Cell polarization is crucial for the functioning of all organisms. The cytoskeleton is central to the process but its role in symmetry breaking is poorly understood. We study cell polarization when fission yeast cells exit starvation. We show that the basis of polarity generation is de novo sterol biosynthesis, cell surface delivery of sterols, and their recruitment to the cell poles. This involves four phases occurring independent of the polarity factor cdc42p. Initially, multiple, randomly distributed sterol-rich membrane (SRM) domains form at the plasma membrane, independent of the cytoskeleton and cell growth. These domains provide platforms on which the growth and polarity machinery assembles. SRM domains are then polarized by the microtubule-dependent polarity factor tea1p, which prepares for monopolar growth initiation and later switching to bipolar growth. SRM polarization requires F-actin but not the F-actin organizing polarity factors for3p and bud6p. We conclude that SRMs are key to cell polarization.

Effect of Myxoma Virus Species Jump on Iberian Hare Populations.

The myxoma virus species jump from European rabbits (Oryctolagus cuniculus) to Iberian hares (Lepus granatensis) has raised concerns. We assess the decline suffered by Iberian hare populations on the Iberian Peninsula and discuss the association between the effect of myxomatosis and the average abundance index, which we estimated by using hunting bags.

Pressure ulcers during the COVID-19 pandemic in intensive care:A multicenter cohort study.

AIM: The objective of the present study is twofold: to describe the prevalence and incidence of pressure ulcers (PUs) among ICU patients during the COVID-19 pandemic, and to identify the risk factors associated with the development of PUs in this cohort of ICU patients. MATERIALS AND METHODS: Retrospective cohort study of adult critical care patients admitted in two general ICUs of two different countries (Sweden and Portugal) between March 1st, 2020, and April 30th, 2021, through the analysis of the electronic health record database. The prevalence and incidence were calculated, and a multivariate logistic-regression model was used to calculate odds ratios (ORs), of possible risk factors of PU development. RESULTS: The sample consisted of 1717 patients. The overall prevalence of PU was 15.3 %, and the incidence of ICU-acquired PUs was 14.1 %. Most of the pressure ulcers documented in this study were at the anterior part of the body (45.35 %) and regarding classification, Category 2 (38.40 %) and Category 3 (22.71 %) pressure ulcers together accounted for over fifty percent of the cases recorded. In the multivariate logistic regression model for PU, age, having COVID-19 (OR = 1.58, 95 % CI: 1.20-2.09), use of mechanical ventilation (OR = 1.49, 95 % CI: 1.13 = 1.97), use of vasopressors (OR = 1.31, 95 % CI: 1.00-1.70), having a Braden risk score ≤16 at admission (OR = 1.63; 95 % CI: 1.04-2.56), and length of stay (LOS) (OR = 1.43, 95 % CI 1.03-2.00 if LOS 90-260 h, OR = 2.34, 95 % CI: 1.63-3.35 if LOS >260 h) were associated with the likelihood of developing an ICU-acquired PUs. CONCLUSION: When adjusted for covariates patients with COVID-19 had a higher risk for PU development during the ICU stay compared to patients without COVID-19. Health care personnel in ICU may consider incorporating COVID-19, age, use of mechanical ventilation, vasopressors and estimated LOS in addition to a comprehensive risk assessment including both a risk score and clinical assessment.

Heel skin microclimate control: Secondary analysis of a self-controlled randomized clinical trial.

OBJECTIVE: this study was undertaken to evaluate the efficacy of multilayer polyurethane foam with silicone (MPF) compared to transparent polyurethane film (TPF) dressings in the control of heel skin microclimate (temperature and moisture) of hospitalized patients undergoing elective surgeries. METHOD: the study took of a secondary analysis of a randomized self-controlled trial, involving patients undergoing elective surgical procedure of cardiac and gastrointestinal specialties in a university hospital in southern Brazil, from March 2019 to February 2020. Patients served as their own control, with their heels randomly allocated to either TPF (control) or MPF (intervention). Skin temperature was measured using a digital infrared thermometer; and moisture determined through capacitance, at the beginning and end of surgery. The study was registered in the Brazilian Registry of Clinical Trials: RBR-5GKNG5. RESULTS: significant difference in the microclimate variables were observed when the groups (intervention and control) and the timepoint of measurement (beginning and end of surgery) were compared. When assessing temperature, an increase (+3.3 °C) was observed with TPF and a decrease (-7.4 °C) was recorded with MPF. Regarding skin moisture, an increase in moisture (+14.6 AU) was recorded with TPF and a slight decrease (-0.3 AU) with MPF. CONCLUSIONS: The findings of this study suggest that MPF is more effective than TPF in controlling skin microclimate (temperature and moisture) in heels skin of hospitalized patients undergoing elective surgeries. However, this control should be better investigated in other studies.

Fluid handling by foam wound dressings: From engineering theory to advanced laboratory performance evaluations.

This article describes the contemporary bioengineering theory and practice of evaluating the fluid handling performance of foam-based dressings, with focus on the important and clinically relevant engineering structure-function relationships and on advanced laboratory testing methods for pre-clinical quantitative assessments of this common type of wound dressings. The effects of key wound dressing material-related and treatment-related physical factors on the absorbency and overall fluid handling of foam-based dressings are thoroughly and quantitively analysed. Discussions include exudate viscosity and temperature, action of mechanical forces and the dressing microstructure and associated interactions. Based on this comprehensive review, we propose a newly developed testing method, experimental metrics and clinical benchmarks that are clinically relevant and can set the standard for robust fluid handling performance evaluations. The purpose of this evaluative framework is to translate the physical characteristics and performance determinants of a foam dressing into achievable best clinical outcomes. These guiding principles are key to distinguishing desirable properties of a dressing that contribute to optimal performance in clinical settings.

Integrating factors associated with complex wound healing into a mobile application: Findings from a cohort study.

Complex, chronic or hard-to-heal wounds are a prevalent health problem worldwide, with significant physical, psychological and social consequences. This study aims to identify factors associated with the healing process of these wounds and develop a mobile application for wound care that incorporates these factors. A prospective multicentre cohort study was conducted in nine health units in Portugal, involving data collection through a mobile application by nurses from April to October 2022. The study followed 46 patients with 57 wounds for up to 5 weeks, conducting six evaluations. Healing time was the main outcome measure, analysed using the Mann-Whitney test and three Cox regression models to calculate risk ratios. The study sample comprised various wound types, with pressure ulcers being the most common (61.4%), followed by venous leg ulcers (17.5%) and diabetic foot ulcers (8.8%). Factors that were found to impair the wound healing process included chronic kidney disease (U = 13.50; p = 0.046), obesity (U = 18.0; p = 0.021), non-adherence to treatment (U = 1.0; p = 0.029) and interference of the wound with daily routines (U = 11.0; p = 0.028). Risk factors for delayed healing over time were identified as bone involvement (RR 3.91; p < 0.001), presence of odour (RR 3.36; p = 0.007), presence of neuropathy (RR 2.49; p = 0.002), use of anti-inflammatory drugs (RR 2.45; p = 0.011), stalled wound (RR 2.26; p = 0.022), greater width (RR 2.03; p = 0.002), greater depth (RR 1.72; p = 0.036) and a high score on the healing scale (RR 1.21; p = 0.001). Integrating the identified risk factors for delayed healing into the assessment of patients and incorporating them into a mobile application can enhance decision-making in wound care.

Performance evaluate of different chemometrics formalisms used for prostate cancer diagnosis by NMR-based metabolomics.

INTRODUCTION: In general, two characteristics are ever present in NMR-based metabolomics studies: (1) they are assays aiming to classify the samples in different groups, and (2) the number of samples is smaller than the feature (chemical shift) number. It is also common to observe imbalanced datasets due to the sampling method and/or inclusion criteria. These situations can cause overfitting. However, appropriate feature selection and classification methods can be useful to solve this issue. OBJECTIVES: Investigate the performance of metabolomics models built from the association between feature selectors, the absence of feature selection, and classification algorithms, as well as use the best performance model as an NMR-based metabolomic method for prostate cancer diagnosis. METHODS: We evaluated the performance of NMR-based metabolomics models for prostate cancer diagnosis using seven feature selectors and five classification formalisms. We also obtained metabolomics models without feature selection. In this study, thirty-eight volunteers with a positive diagnosis of prostate cancer and twenty-three healthy volunteers were enrolled. RESULTS: Thirty-eight models obtained were evaluated using AUROC, accuracy, sensitivity, specificity, and kappa's index values. The best result was obtained when Genetic Algorithm was used with Linear Discriminant Analysis with 0.92 sensitivity, 0.83 specificity, and 0.88 accuracy. CONCLUSION: The results show that the pick of a proper feature selection method and classification model, and a resampling method can avoid overfitting in a small metabolomic dataset. Furthermore, this approach would decrease the number of biopsies and optimize patient follow-up. 1H NMR-based metabolomics promises to be a non-invasive tool in prostate cancer diagnosis.

The potential role of scavenging flies as mechanical vectors of Lagovirus europaeus/GI.2.

The European rabbit (Oryctolagus cuniculus) populations of the Iberian Peninsula have been severely affected by the emergence of the rabbit haemorrhagic disease virus (RHDV) Lagovirus europaeus/GI.2 (RHDV2/b). Bushflies and blowflies (Muscidae and Calliphoridae families, respectively) are important RHDV vectors in Oceania, but their epidemiological role is unknown in the native range of the European rabbit. In this study, scavenging flies were collected between June 2018 and February 2019 in baited traps at one site in southern Portugal, alongside a longitudinal capture-mark-recapture study of a wild European rabbit population, aiming to provide evidence of mechanical transmission of GI.2 by flies. Fly abundance, particularly from Calliphoridae and Muscidae families, peaked in October 2018 and in February 2019. By employing molecular tools, we were able to detect the presence of GI.2 in flies belonging to the families Calliphoridae, Muscidae, Fanniidae and Drosophilidae. The positive samples were detected during an RHD outbreak and absent in samples collected when no evidence of viral circulation in the local rabbit population was found. We were able to sequence a short viral genomic fragment, confirming its identity as RHDV GI.2. The results suggest that scavenging flies may act as mechanical vectors of GI.2 in the native range of the southwestern Iberian subspecies O. cuniculus algirus. Future studies should better assess their potential in the epidemiology of RHD and as a tool for monitoring viral circulation in the field.

The frequency and characteristics of epinephrine use during in-flight allergic events.

BACKGROUND: Allergic reactions account for 2% to 4% of medical events in-flight and 5.5% of all medical events in passengers 18 years and under. OBJECTIVE: To evaluate the incidence of in-flight allergic events including availability, use of epinephrine, and final patient outcome. METHODS: We conducted a retrospective study of the ground-based medical service (GBMS) database from January 2017 to December 2019 for all allergic events and epinephrine utilization. RESULTS: A total of 140,579 in-flight medical events (IFMEs) were initially retrieved from the period between January, 2017 and December, 2019, of which 4230 (3.0%) unique cases were identified as allergic events. Epinephrine administration was recommended in 398 passengers by GBMS. Of those, 328 (82.4%) ultimately received at least 1 dose of epinephrine. In multivariate analysis, there was a significant difference in the involvement of volunteers (odds ratio [OR], 3.19; P value < .001; 95% confidence interval [CI], 2.43-4.16), availability of autoinjectors (OR, 2; P value < .001; 95% CI, 1.55-2.58), flight diversion (OR, 11.21; P value < .001; 95% CI, 3.60-34.89), and hospital transport (OR, 6.58; P value < .001; 95% CI, 4.62-9.38) between the 2 groups. Passengers older than 12 years of age were at a higher risk for epinephrine administration. In the secondary analysis of 51 airlines that consistently use GBMS for all IFMEs, the incidence of allergic events was found to be 0.91 cases per million passengers. The incidence of severe in-flight allergic emergencies requiring epinephrine administration was 0.08 cases per million passengers or 12.5 million passengers for 1 event. CONCLUSION: IFME requiring epinephrine administration is rare with an incidence rate of 1 event in 12.5 million passengers. The risk for epinephrine administration is higher in passengers more than 12 years of age and is associated with significantly higher flight diversion, hospital transport, and involvement of medical volunteers.

Individual and combined toxicity of imidacloprid and two seed dressing insecticides on collembolans Folsomia candida.

The aim of this study was to examine the chronic toxicity of imidacloprid (IMI), clothianidin (CLO) and fipronil (FIP) as a single exposure, as well as binary mixtures of IMI with CLO or FIP toward collembolans Folsomia candida, which are fauna present in the soil. Chronic toxicity assays were performed following an ISO guideline in a Tropical Artificial Soil (TAS), and the influence on the number and growth of the juveniles produced were determined. The range of nominal concentrations used in the tests with the individual compounds was 0.08-1.28 mg/kg (IMI), 0.079-1.264 mg/kg (FIP) and 0.007-0.112 mg/kg (CLO), whereas the mixture assays were performed with half the value used in the tests with individual compounds. Based upon single exposures, IMI produced a similar impact of reducing reproduction by 50% (EC50 ranging from 0.74 to 0.85 mg/kg) compared to FIP (EC50 = 0.78 mg/kg), whereas CLO was the most toxic to F. candida (EC50 = 0.08 mg/kg). Their mixtures generally resulted in a diminished effect on reproduction, as evidenced by the higher EC50 values. In contrast, in the case of the IMI+FIP combination at high concentrations at the EC50 level, a synergistic effect on toxicity was observed. The single exposure to the three insecticides and the mixture of IMI-FIP also decreased the size of generated juveniles, which was evidenced by the reduction in the proportion of large juveniles and increased proportion of small juveniles. However, both binary mixtures (IMI-FIP and IMI-CLO) presented antagonistic effects as evidenced by less than expected reductions in growth. Data on the toxic effects of IMI in a mixture with other seed dressing insecticides to collembolans provides useful information to environmental risk assessors by diminishing the uncertainties on the ecological risk of exposure to pesticides, enabling soil management degradation by utilizing multiple insecticides.

Influence of temperature and soil moisture on the toxic potential of clothianidin to collembolan Folsomia candida in a tropical field soil.

Climate change can alter the toxic effects of pesticides on soil invertebrates. However, the nature and magnitude of the influence of climatic factors on clothianidin impacts in tropical soils are still unknown. The influence of increasing atmospheric temperature and the reduction in soil moisture on the toxicity and risk of clothianidin (seed dressing formulation Inside FS®) were assessed through chronic toxicity tests with collembolans Folsomia candida in a tropical field soil (Entisol). The risk of clothianidin for collembolans was estimated using the Toxicity-Exposure Ratio (TER) approach. Organisms were exposed to increasing clothianidin concentrations at 20, 25 and 27 °C in combination with two soil moisture conditions (30 and 60% of the maximum water holding capacity-WHC). The effect of temperature and soil moisture content on clothianidin toxicity was verified through the number of F. candida juveniles generated after 28 days of exposure to the spiked soil. The toxicities estimated at 25 °C (EC50_30%WHC = 0.014 mg kg-1; EC50_60%WHC = 0.010 mg kg-1) and 27 °C (EC50_30%WHC = 0.006 mg kg-1; EC50_60%WHC = 0.007 mg kg-1) were 2.9-3.0-fold (25 °C) and 4.3-6.7-fold (27 °C) higher than those found at 20 °C (EC50_30%WHC = 0.040 mg kg-1; EC50_60%WHC = 0.030 mg kg-1), indicating that clothianidin toxicity increases with temperature. No clear influence of soil moisture content on clothianidin toxicity could be observed once the EC50 values estimated at 30% and 60% WHC, within the same temperature, did not significantly differ. A significant risk was detected in all temperatures and soil moisture scenarios studied, and the TER values indicate that the risk can increase with increasing temperatures. Our results revealed that temperature could overlap with soil moisture in regulating clothianidin toxicity and reinforce the importance of including climatic factors in the prospective risk assessment of pesticides.

Clinical prediction models and risk tools for early detection of patients at risk of surgical site infection and surgical wound dehiscence: a scoping review.

OBJECTIVE: Despite advances in surgical techniques, intraoperative practice and a plethora of advanced wound therapies, surgical wound complications (SWCs), such as surgical site infection (SSI) and surgical wound dehiscence (SWD), continue to pose a considerable burden to the patient and healthcare setting. Predicting those patients at risk of a SWC may give patients and healthcare providers the opportunity to implement a tailored prevention plan or potentially ameliorate known risk factors to improve patient postoperative outcomes. METHOD: A scoping review of the literature for studies which reported predictive power and internal/external validity of risk tools for clinical use in predicting patients at risk of SWCs after surgery was conducted. An electronic search of three databases and two registries was carried out with date restrictions. The search terms included 'prediction surgical site infection' and 'prediction surgical wound dehiscence'. RESULTS: A total of 73 records were identified from the database search, of which six studies met the inclusion criteria. Of these, the majority of validated risk tools were predominantly within the cardiothoracic domain, and targeted morbidity and mortality outcomes. There were four risk tools specifically targeting SWCs following surgery. CONCLUSION: The findings of this review have highlighted an absence of well-developed risk tools specifically for SSI and/or SWD in most surgical populations. This review suggests that further research is required for the development and clinical implementation of rigorously validated and fit-for-purpose risk tools for predicting patients at risk of SWCs following surgery. The ability to predict such patients enables the implementation of preventive strategies, such as the use of prophylactic antibiotics, delayed timing of surgery, or advanced wound therapies following a procedure.

The development of a core outcome set for clinical effectiveness studies of bordered foam dressings in the treatment of complex wounds.

AIM: The aim of this project was to develop a core outcome set (COS) for clinical effectiveness studies of bordered foam dressings in the treatment of complex wounds. METHODS: The research project followed the Core Outcome Measures in Effectiveness Trials (COMET) initiative and consisted of two phases. The first phase prepared the background and process, while the second phase had three steps: outcome list generation via systematic review and qualitative study, Delphi consensus study, and consensus meeting. The study has been registered in the Core Outcome Measures in Effectiveness Trials database. RESULTS: The systematic review resulted in 82 outcomes and 20 additional outcomes were obtained during the interviews. After refinement, 111 panellists from 23 countries rated a list of 51 outcomes. In the following consensus meeting, six outcomes were prioritized to be included in the core outcome set. After the consensus meeting, a patient-reported outcome was added to the core outcome set. CONCLUSION: The COS for evaluating the effectiveness of bordered foam dressings in treating complex wounds includes 7 outcomes: "ability to stay in place", "leakage", "pain", "dressing related periwound skin changes", "change in wound size over time", and "overall satisfaction". These identified outcomes are correlated with contemporary bioengineering testing and evaluation methods for dressing performance, which underpins the need for a close multidisciplinary collaboration to advance the field of wound dressings. The outcome 'overall satisfaction' reflects the impact of complex wounds and their treatment on a patient's daily life. The use of these outcomes is recommended to improve data synthesis and promote evidence-based practice. Future developments in COS development involve creating measurement instruments and relevant endpoints for these outcomes.

Prognostic factors for delayed healing of complex wounds in adults: A scoping review.

Complex or hard-to-heal wounds continue to be a challenge because of the negative impact they have on patients, caregivers, and all the associated costs. This study aimed to identify prognostic factors for the delayed healing of complex wounds. Five databases and grey literature were the sources used to research adults with pressure ulcers/injuries, venous leg ulcers, critical limb-threatening ischaemia, or diabetic foot ulcers and report the prognostic factors for delayed healing in all care settings. In the last 5 years, a total of 42 original peer-reviewed articles were deemed eligible for this scoping review that followed the JBI recommendations and checklist PRISMA-ScR. The most frequent prognostic factors found with statistical significance coinciding with various wound aetiologies were: gender (male), renal disease, diabetes, peripheral arterial disease, the decline in activities of daily life, wound duration, wound area, wound location, high-stage WIfI classification, gangrene, infection, previous ulcers, and low ankle brachial index. It will be essential to apply critical appraisal tools and assessment risk of bias to the included studies, making it possible to make recommendations for clinical practice and build prognostic models. Future studies are recommended because the potential for healing through identification of prognostic factors can be determined, thus allowing an appropriate therapeutic plan to be developed.

Mechanical and contact characteristics of foam materials within wound dressings: Theoretical and practical considerations in treatment.

In the treatment of acute and chronic wounds, the clinical performance of a given foam-based dressing, and, ultimately, the wound healing and cost of care outcomes are strongly influenced by the mechanical performance of the foam material/s within that dressing. Most aspects of the mechanical performance of foam materials, for example, their stiffness, frictional properties, conformability, swelling characteristics and durability, and the overall mechanical protection provided by a foam-based dressing to a wound strongly depend on the microstructure of the foam components, particularly on their microtopography, density and porosity. This article, therefore, provides, for the first time, a comprehensive, self-inclusive compilation of clinically relevant theoretical and practical considerations, based on published analytical and experimental research as well as clinical experience related to the mechanical performance of foams in foam-based wound dressings. The current bioengineering information is useful for establishing understanding of the importance of mechanical properties of foams in foam-based dressings among clinicians and researchers in industry and academia, and other potential stakeholders in the wound care field, for example, regulators and buyers. This information is also particularly important for the development of standardised test methods for the evaluation of foam-based wound dressings and resulting standard mechanical performance metrics for these dressings.

Clinical and cost effectiveness of a system for turning and positioning intensive care unit patients, when compared to usual care turning and positioning devices, for the prevention of hospital-acquired pressure injuries. A randomised controlled trial.

Pressure injuries affect 13.1% to 45.5% of patients in the intensive care unit and lead to pain and discomfort for patients, burden on healthcare providers, and unnecessary cost to the health system. Turning and positioning systems offer improvements on usual care devices, however the evidence of the effectiveness of such systems is still emerging. We conducted an investigator initiated, prospective, single centre, two group, non-blinded, randomised controlled trial to determine the effectiveness of a system for turning and positioning intensive care unit patients, when compared to usual care turning and positioning devices, for preventing PIs. The trial was prematurely discontinued after enrolment of 78 participants due to COVID-19 pandemic related challenges and lower than expected enrolment rate. The study groups were comparable on baseline characteristics and adherence to the interventions was high. Four participants developed a PI (in the sacral, ischial tuberosity or buttock region), n = 2 each in the intervention and control group. Each participant developed one PI. As the trial is underpowered, these findings do not provide an indication of the clinical effectiveness of the interventions. There was no participant drop-out or withdrawal and there were no adverse events, device deficiencies, or adverse device effects identified or reported. The results of our study (in particular those pertaining to enrolment, intervention adherence and safety) provide considerations for future trials that seek to investigate how to prevent PIs among ICU patients.

Clinical performance characteristics for bordered foam dressings in the treatment of complex wounds: An international wound dressing technology expert panel review.

The aim of this article is to identify and describe clinical practice performance characteristics for bordered foam dressings in the treatment of complex wounds. Our recently published systematic review of outcomes and applied measurement instruments for the use of bordered foam dressings in complex wounds has led to us identifying a range of important clinical and patient-centred issues related to this dressing class. Specifically, here, we focus on an overview of performance criteria in the areas of application, adhesion, exudate management and debridement functions of bordered foam dressings. Our hope is that by highlighting the clinical performance criteria, future testing standards for wound dressings will more closely match our clinical expectations and, thereby, assist clinicians to make better wound treatment choices based on meaningful and clinically relevant dressing product performance standards. complex wounds, complex wound care, treatment, bordered foam dressings, dressing performance.

Bagaza Virus in Wild Birds, Portugal, 2021.

Bagaza virus emerged in Spain in 2010 and was not reported in other countries in Europe until 2021, when the virus was detected by molecular methods in a corn bunting and several red-legged partridges in Portugal. Sequencing revealed high similarity between the 2021 strains from Portugal and the 2010 strains from Spain.

The evolutionary pathways for local adaptation in mountain hares.

Understanding the evolution of local adaptations is a central aim of evolutionary biology and key for the identification of unique populations and lineages of conservation relevance. By combining RAD sequencing and whole-genome sequencing, we identify genetic signatures of local adaptation in mountain hares (Lepus timidus) from isolated and distinctive habitats of its wide distribution: Ireland, the Alps and Fennoscandia. Demographic modelling suggested that the split of these mountain hares occurred around 20 thousand years ago, providing the opportunity to study adaptive evolution over a short timescale. Using genome-wide scans, we identified signatures of extreme differentiation among hares from distinct geographic areas that overlap with area-specific selective sweeps, suggesting targets for local adaptation. Several identified candidate genes are associated with traits related to the uniqueness of the different environments inhabited by the three groups of mountain hares, including coat colour, ability to live at high altitudes and variation in body size. In Irish mountain hares, a variant of ASIP, a gene previously implicated in introgression-driven winter coat colour variation in mountain and snowshoe hares (L. americanus), may underlie brown winter coats, reinforcing the repeated nature of evolution at ASIP moulding adaptive seasonal colouration. Comparative genomic analyses across several hare species suggested that mountain hares' adaptive variants appear predominantly species-specific. However, using coalescent simulations, we also show instances where the candidate adaptive variants have been introduced via introgressive hybridization. Our study shows that standing adaptive variation, including that introgressed from other species, was a crucial component of the post-glacial dynamics of species.

The Legacy of Recurrent Introgression during the Radiation of Hares.

Hybridization may often be an important source of adaptive variation, but the extent and long-term impacts of introgression have seldom been evaluated in the phylogenetic context of a radiation. Hares (Lepus) represent a widespread mammalian radiation of 32 extant species characterized by striking ecological adaptations and recurrent admixture. To understand the relevance of introgressive hybridization during the diversification of Lepus, we analyzed whole exome sequences (61.7 Mb) from 15 species of hares (1-4 individuals per species), spanning the global distribution of the genus, and two outgroups. We used a coalescent framework to infer species relationships and divergence times, despite extensive genealogical discordance. We found high levels of allele sharing among species and show that this reflects extensive incomplete lineage sorting and temporally layered hybridization. Our results revealed recurrent introgression at all stages along the Lepus radiation, including recent gene flow between extant species since the last glacial maximum but also pervasive ancient introgression occurring since near the origin of the hare lineages. We show that ancient hybridization between northern hemisphere species has resulted in shared variation of potential adaptive relevance to highly seasonal environments, including genes involved in circadian rhythm regulation, pigmentation, and thermoregulation. Our results illustrate how the genetic legacy of ancestral hybridization may persist across a radiation, leaving a long-lasting signature of shared genetic variation that may contribute to adaptation. [Adaptation; ancient introgression; hybridization; Lepus; phylogenomics.].