Taxonomy and pathology of Togninia (Diaporthales) and its Phaeoacremonium anamorphs.

The genus Togninia (Diaporthales, Togniniaceae) is here monographed along with its Phaeoacremonium (Pm.) anamorphs. Ten species of Togninia and 22 species of Phaeoacremonium are treated. Several new species of Togninia (T.) are described, namely T. argentinensis (anamorph Pm. argentinense), T. austroafricana (anamorph Pm. austroafricanum), T. krajdenii, T. parasitica, T. rubrigena and T. viticola. New species of Phaeoacremonium include Pm. novae-zealandiae (teleomorph T. novae-zealandiae), Pm. iranianum, Pm. sphinctrophorum and Pm. theobromatis. Species can be identified based on their cultural and morphological characters, supported by DNA data derived from partial sequences of the actin and ß-tubulin genes. Phylogenies of the SSU and LSU rRNA genes were used to determine whether Togninia has more affinity with the Calosphaeriales or the Diaporthales. The results confirmed that Togninia had a higher affinity to the Diaporthales than the Calosphaeriales. Examination of type specimens revealed that T. cornicola, T. vasculosa, T. rhododendri, T. minima var. timidula and T. villosa, were not members of Togninia. The new combinations Calosphaeria cornicola, Calosphaeria rhododendri, Calosphaeria transversa, Calosphaeria tumidula, Calosphaeria vasculosa and Jattaea villosa are proposed. Species of Phaeoacremonium are known vascular plant pathogens causing wilting and dieback of woody plants. The most prominent diseases in which they are involved are Petri disease and esca, which occur on grapevines and are caused by a complex of fungi, often including multiple species of Phaeoacremonium. Various Phaeoacremonium species are opportunistic fungi on humans and cause phaeohyphomycosis. The correct and rapid identification of Phaeoacremonium species is important to facilitate the understanding of their involvement in plant as well as human disease. A rapid identification method was developed for the 22 species of Phaeacremonium. It involved the use of 23 species-specific primers, including 20 primers targeting the ß-tubulin gene and three targeting the actin gene. These primers can be used in 14 multiplex reactions. Additionally, a multiple-entry electronic key based on morphological, cultural and ß-tubulin sequence data was developed to facilitate phenotypic and sequence-based species identification of the different Phaeoacremonium species. Separate dichotomous keys are provided for the identification of the Togninia and Phaeoacremonium species. Keys for the identification of Phaeoacremonium-like fungi and the genera related to Togninia are also provided. The mating strategy of several Togninia species was investigated with ascospores obtained from fertile perithecia produced in vitro. Togninia argentinensis and T. novae-zealandiae have homothallic mating systems, whereas T. austroafricana, T. krajdenii, T. minima, T. parasitica, T. rubrigena and T. viticola were heterothallic.

Monte Carlo Simulations of Metal-Poor Star Clusters

Metal-poor globular clusters (GCs) can provide a probe of the earliest epoch of star formation in the Universe, being the oldest stellar systems observable. In addition, young and intermediate-age low-metallicity GCs are present in external galaxies. Nevertheless, inferring their evolutionary status by using integrated properties may suffer from large \emph{intrinsic} uncertainty caused by the discrete nature of stars in stellar systems, especially in the case of faint objects. In this paper, we evaluate the \emph{intrinsic} uncertainty (due to statistical effects) affecting the integrated colours and mass--to--light ratios as a function of the cluster integrated visual magnitude ($M_V^{tot}$), which represents a quantity directly measured. Our approach is based on Monte Carlo techniques for randomly generating stars distributed according to the cluster's mass function. Integrated colours and mass--to--light ratios in different photometric bands are checked to be in good agreement with the observational values of low-metallicity Galactic clusters. We present integrated colours and mass--to--light ratios as a function of age for different assumptions on the cluster total $V$ magnitude. We find that the emph{intrinsic} uncertainty cannot be neglected. In particular, in models with $M_V^{tot}=-4$ the broad-band colours show an \emph{intrinsic} uncertainty so high as to prevent precise age evaluation of the cluster. Finally, the present predictions are compared with recent results available in the literature, showing in some cases non-negligible differences.Comment: 18 pages, 12 figures, A&A accepte

Tracing the evolution of NGC6397 through the chemical composition of its stellar populations

With the aim to constrain multiple populations in the metal-poor globular cluster NGC6397, we analyse and discuss the chemical compositions of a large number of elements in 21 red giant branch stars. High-resolution spectra were obtained with the FLAMES/UVES spectrograph on VLT. We have determined non-LTE abundances of Na and LTE abundances for the remaining 21 elements, including O, Mg, Al, alpha, iron-peak, and neutron-capture elements, many of which have not previously been analysed for this cluster. We have also considered the influence of possible He enrichment in the analysis of stellar spectra. We find that the Na abundances of evolved, as well as unevolved, stars show a distinct bimodality, which suggests the presence of two stellar populations; one primordial stellar generation with composition similar to field stars, and a second generation that is enriched in material processed through hydrogen-burning (enriched in Na and Al and depleted in O and Mg). The cluster is dominated (75%) by the second generation. The red giant branch show a similar bimodal distribution in the Stroemgren colour index c_y=c_1-(b-y), implying a large difference also in N abundance. The two populations have the same composition of all analysed elements heavier than Al, within the measurement uncertainty of the analysis, with the possible exception of [Y/Fe]. Using two stars with close to identical stellar parameters, one from each generation, we estimate the difference in He content, Delta Y=0.01+-0.06, given the assumption that the mass fraction of iron is the same for the stars. Finally, we show that winds from fast rotating massive stars of the first generation can be held responsible for the abundance patterns observed in NGC6397 second generation long-lived stars and estimate that the initial mass of the cluster were at least ten times higher than its present-day value.Comment: 13 pages + appendix with two tables. Accepted for publication in A&A. v2: minor language corrections and Table A.2. correcte

INSL6 Protective Effects in Heart Failure

Background The insulin/insulin‐like growth factor/relaxin family represents a group of structurally related but functionally diverse proteins. The family member relaxin‐2 has been evaluated in clinical trials for its efficacy in the treatment of acute heart failure. In this study, we assessed the role of insulin‐like peptide 6 (INSL6), another member of this protein family, in murine heart failure models using genetic loss‐of‐function and protein delivery methods. Methods and Results Insl6‐deficient and wild‐type (C57BL/6N) mice were administered angiotensin II or isoproterenol via continuous infusion with an osmotic pump or via intraperitoneal injection once a day, respectively, for 2 weeks. In both models, Insl6‐knockout mice exhibited greater cardiac systolic dysfunction and left ventricular dilatation. Cardiac dysfunction in the Insl6‐knockout mice was associated with more extensive cardiac fibrosis and greater expression of fibrosis‐associated genes. The continuous infusion of chemically synthesized INSL6 significantly attenuated left ventricular systolic dysfunction and cardiac fibrosis induced by isoproterenol infusion. Gene expression profiling suggests liver X receptor/retinoid X receptor signaling is activated in the isoproterenol‐challenged hearts treated with INSL6 protein. Conclusions Endogenous Insl6 protein inhibits cardiac systolic dysfunction and cardiac fibrosis in angiotensin II– and isoproterenol‐induced cardiac stress models. The administration of recombinant INSL6 protein could have utility for the treatment of heart failure and cardiac fibrosis

Common and rare variant association analyses in amyotrophic lateral sclerosis identify 15 risk loci with distinct genetic architectures and neuron-specific biology

A cross-ancestry genome-wide association meta-analysis of amyotrophic lateral sclerosis (ALS) including 29,612 patients with ALS and 122,656 controls identifies 15 risk loci with distinct genetic architectures and neuron-specific biology. Amyotrophic lateral sclerosis (ALS) is a fatal neurodegenerative disease with a lifetime risk of one in 350 people and an unmet need for disease-modifying therapies. We conducted a cross-ancestry genome-wide association study (GWAS) including 29,612 patients with ALS and 122,656 controls, which identified 15 risk loci. When combined with 8,953 individuals with whole-genome sequencing (6,538 patients, 2,415 controls) and a large cortex-derived expression quantitative trait locus (eQTL) dataset (MetaBrain), analyses revealed locus-specific genetic architectures in which we prioritized genes either through rare variants, short tandem repeats or regulatory effects. ALS-associated risk loci were shared with multiple traits within the neurodegenerative spectrum but with distinct enrichment patterns across brain regions and cell types. Of the environmental and lifestyle risk factors obtained from the literature, Mendelian randomization analyses indicated a causal role for high cholesterol levels. The combination of all ALS-associated signals reveals a role for perturbations in vesicle-mediated transport and autophagy and provides evidence for cell-autonomous disease initiation in glutamatergic neurons

Mortality and pulmonary complications in patients undergoing surgery with perioperative SARS-CoV-2 infection: an international cohort study

Background: The impact of severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) on postoperative recovery needs to be understood to inform clinical decision making during and after the COVID-19 pandemic. This study reports 30-day mortality and pulmonary complication rates in patients with perioperative SARS-CoV-2 infection. Methods: This international, multicentre, cohort study at 235 hospitals in 24 countries included all patients undergoing surgery who had SARS-CoV-2 infection confirmed within 7 days before or 30 days after surgery. The primary outcome measure was 30-day postoperative mortality and was assessed in all enrolled patients. The main secondary outcome measure was pulmonary complications, defined as pneumonia, acute respiratory distress syndrome, or unexpected postoperative ventilation. Findings: This analysis includes 1128 patients who had surgery between Jan 1 and March 31, 2020, of whom 835 (74·0%) had emergency surgery and 280 (24·8%) had elective surgery. SARS-CoV-2 infection was confirmed preoperatively in 294 (26·1%) patients. 30-day mortality was 23·8% (268 of 1128). Pulmonary complications occurred in 577 (51·2%) of 1128 patients; 30-day mortality in these patients was 38·0% (219 of 577), accounting for 81·7% (219 of 268) of all deaths. In adjusted analyses, 30-day mortality was associated with male sex (odds ratio 1·75 [95% CI 1·28–2·40], p\textless0·0001), age 70 years or older versus younger than 70 years (2·30 [1·65–3·22], p\textless0·0001), American Society of Anesthesiologists grades 3–5 versus grades 1–2 (2·35 [1·57–3·53], p\textless0·0001), malignant versus benign or obstetric diagnosis (1·55 [1·01–2·39], p=0·046), emergency versus elective surgery (1·67 [1·06–2·63], p=0·026), and major versus minor surgery (1·52 [1·01–2·31], p=0·047). Interpretation: Postoperative pulmonary complications occur in half of patients with perioperative SARS-CoV-2 infection and are associated with high mortality. Thresholds for surgery during the COVID-19 pandemic should be higher than during normal practice, particularly in men aged 70 years and older. Consideration should be given for postponing non-urgent procedures and promoting non-operative treatment to delay or avoid the need for surgery. Funding: National Institute for Health Research (NIHR), Association of Coloproctology of Great Britain and Ireland, Bowel and Cancer Research, Bowel Disease Research Foundation, Association of Upper Gastrointestinal Surgeons, British Association of Surgical Oncology, British Gynaecological Cancer Society, European Society of Coloproctology, NIHR Academy, Sarcoma UK, Vascular Society for Great Britain and Ireland, and Yorkshire Cancer Research

Apoptotic cell death in disease-Current understanding of the NCCD 2023

Apoptosis is a form of regulated cell death (RCD) that involves proteases of the caspase family. Pharmacological and genetic strategies that experimentally inhibit or delay apoptosis in mammalian systems have elucidated the key contribution of this process not only to (post-)embryonic development and adult tissue homeostasis, but also to the etiology of multiple human disorders. Consistent with this notion, while defects in the molecular machinery for apoptotic cell death impair organismal development and promote oncogenesis, the unwarranted activation of apoptosis promotes cell loss and tissue damage in the context of various neurological, cardiovascular, renal, hepatic, infectious, neoplastic and inflammatory conditions. Here, the Nomenclature Committee on Cell Death (NCCD) gathered to critically summarize an abundant pre-clinical literature mechanistically linking the core apoptotic apparatus to organismal homeostasis in the context of disease