On the mass and wind luminosity of young Galactic open clusters in Gaia DR2

Context. Star clusters constitute a relevant part of the stellar population in our Galaxy. The feedback processes they exert on the interstellar medium impact multiple physical processes, from the chemical to the dynamical evolution of the Galaxy. In addition, young and massive stellar clusters might act as efficient particle accelerators, possibly contributing to the production of cosmic rays. Aims. We aim at evaluating the wind luminosity driven by the young (< 30 Myr) Galactic open stellar clusters observed by the Gaia space mission, which is crucial to determine the energy channeled into accelerated particles. Methods. To this extent, we develop a method relying on the number, magnitude and line-of-sight extinction of the stars observed per cluster. Assuming that the stellar mass function follows a Kroupa mass distribution, and accounting for the maximum stellar mass allowed by both the parent cluster age and mass, we conservatively estimate the mass and wind luminosity of 387 local clusters within the second data release of Gaia. Results. We compare the results of our computation with recent estimations of young cluster masses. With respect to these, we provide a sample three times more abundant, particularly above a few thousand solar masses, which is of the utmost relevance for predicting the gamma-ray emission resulting from the interaction of accelerated particles. In fact, the cluster wind luminosity distribution we obtain is found to extend up to 3 x 10^38 erg/s, a promising feature in terms of potential particle acceleration scenarios.Comment: 11 pages, 16 figures, comments are welcom

A unified compendium of prokaryotic and viral genomes from over 300 anaerobic digestion microbiomes

BackgroundThe anaerobic digestion process degrades organic matter into simpler compounds and occurs in strictly anaerobic and microaerophilic environments. The process is carried out by a diverse community of microorganisms where each species has a unique role and it has relevant biotechnological applications since it is used for biogas production. Some aspects of the microbiome, including its interaction with phages, remains still unclear: a better comprehension of the community composition and role of each species is crucial for a cured understanding of the carbon cycle in anaerobic systems and improving biogas production.ResultsThe primary objective of this study was to expand our understanding on the anaerobic digestion microbiome by jointly analyzing its prokaryotic and viral components. By integrating 192 additional datasets into a previous metagenomic database, the binning process generated 11,831 metagenome-assembled genomes from 314 metagenome samples published between 2014 and 2022, belonging to 4,568 non-redundant species based on ANI calculation and quality verification. CRISPR analysis on these genomes identified 76 archaeal genomes with active phage interactions. Moreover, single-nucleotide variants further pointed to archaea as the most critical members of the community. Among the MAGs, two methanogenic archaea, Methanothrix sp. 43zhSC_152 and Methanoculleus sp. 52maCN_3230, had the highest number of SNVs, with the latter having almost double the density of most other MAGs.ConclusionsThis study offers a more comprehensive understanding of microbial community structures that thrive at different temperatures. The findings revealed that the fraction of archaeal species characterized at the genome level and reported in public databases is higher than that of bacteria, although still quite limited. The identification of shared spacers between phages and microbes implies a history of phage-bacterial interactions, and specifically lysogenic infections. A significant number of SNVs were identified, primarily comprising synonymous and nonsynonymous variants. Together, the findings indicate that methanogenic archaea are subject to intense selective pressure and suggest that genomic variants play a critical role in the anaerobic digestion process. Overall, this study provides a more balanced and diverse representation of the anaerobic digestion microbiota in terms of geographic location, temperature range and feedstock utilization

Functional characterization of a novel truncating mutation in Lamin A/C gene in a family with a severe cardiomyopathy with conduction defects

Background/Aims: Truncating LMNA gene mutations occur in many inherited cardiomyopathy cases, but the molecular mechanisms involved in the disease they cause have not yet been systematically investigated. Here, we studied a novel frameshift LMNA variant (p.D243Gfs*4) identified in three members of an Italian family co-segregating with a severe form of cardiomyopathy with conduction defects. Methods: HEK293 cells and HL-1 cardiomyocytes were transiently transfected with either Lamin A or D243Gfs*4 tagged with GFP (or mCherry). D243Gfs*4 expression, cellular localization and its effects on diverse cellular mechanisms were evaluated with western blotting, laser-scanning confocal microscopy and video-imaging analysis in single cells. Results: When expressed in HEK293 cells, GFP- (or mCherry)-tagged LMNA D243Gfs*4 colocalized with calnexin within the ER. ER mislocalization of LMNA D243Gfs*4 did not significantly induce ER stress response, abnormal Ca2+ handling and apoptosis when compared with HEK293 cells expressing another truncated mutant of LMNA (R321X) which similarly accumulates within the ER. Of note, HEK293-LMNA D243Gfs*4 cells showed a significant reduction of connexin 43 (CX43) expression level, which was completely rescued by activation of the WNT/β-catenin signaling pathway. When expressed in HL-1 cardiomyocytes, D243Gfs*4 significantly impaired the spontaneous Ca2+ oscillations recorded in these cells as result of propagation of the depolarizing waves through the gap junctions between non-transfected cells surrounding a cell harboring the mutation. Furthermore, mCh-D243Gfs*4 HL-1 cardiomyocytes showed reduced CX43-dependent Lucifer Yellow (LY) loading and propagation. Of note, activation of β-catenin rescued both LY loading and LMNA D243Gfs*4 -HL-1 cells spontaneous activity propagation. Conclusion: Overall, the present results clearly indicate the involvement of the aberrant CX43 expression/activity as a pathogenic mechanism for the conduction defects associated to this LMNA truncating alteration

Exon-trapping assay improves clinical interpretation of COL11A1 and COL11A2 intronic variants in stickler syndrome type 2 and otospondylomegaepiphyseal dysplasia

Stickler syndrome (SS) is a hereditary connective tissue disorder affecting bones, eyes, and hearing. Type 2 SS and the SS variant otospondylomegaepiphyseal dysplasia (OSMED) are caused by deleterious variants in COL11A1 and COL11A2, respectively. In both genes, available database information indicates a high rate of potentially deleterious intronic variants, but published evidence of their biological effect is usually insufficient for a definite clinical interpretation. We report our previously unpublished intronic variants in COL11A1 (c.2241 + 5G&gt;T, c.2809 − 2A&gt;G, c.3168 + 5G&gt;C) and COL11A2 (c.4392 + 1G&gt;A) identified in type 2 SS/OSMED individuals. The pathogenic effect of these variants was first predicted in silico and then investigated by an exon-trapping assay. We demonstrated that all variants can induce exon in-frame deletions, which lead to the synthesis of shorter collagen XI α1 or 2 chains. Lacking residues are located in the α-triple helical region, which has a crucial role in regulating collagen fibrillogenesis. In conclusion, this study suggests that these alternative COL11A1 and COL11A2 transcripts might result in aberrant triple helix collagen. Our approach may help to improve the diagnostic molecular pathway of COL11-related disorder

Transcriptomic and photosynthetic analyses of Synechocystis sp. PCC6803 and Chlorogloeopsis fritschii sp. PCC6912 exposed to an M-dwarf spectrum under an anoxic atmosphere

IntroductionCyanobacteria appeared in the anoxic Archean Earth, evolving for the first time oxygenic photosynthesis and deeply changing the atmosphere by introducing oxygen. Starting possibly from UV-protected environments, characterized by low visible and far-red enriched light spectra, cyanobacteria spread everywhere on Earth thanks to their adaptation capabilities in light harvesting. In the last decade, few cyanobacteria species which can acclimate to far-red light through Far-Red Light Photoacclimation (FaRLiP) have been isolated. FaRLiP cyanobacteria were thus proposed as model organisms to study the origin of oxygenic photosynthesis as well as its possible functionality around stars with high far-red emission, the M-dwarfs. These stars are astrobiological targets, as their longevity could sustain life evolution and they demonstrated to host rocky terrestrial-like exoplanets within their Habitable Zone.MethodsWe studied the acclimation responses of the FaRLiP strain Chlorogloeopsis fritschii sp. PCC6912 and the non-FaRLiP strain Synechocystis sp. PCC6803 to the combination of three simulated light spectra (M-dwarf, solar and far-red) and two atmospheric compositions (oxic, anoxic). We first checked their growth, O2 production and pigment composition, then we studied their transcriptional responses by RNA sequencing under each combination of light spectrum and atmosphere conditions.Results and discussionPCC6803 did not show relevant differences in gene expression when comparing the responses to M-dwarf and solar-simulated lights, while far-red caused a variation in the transcriptional level of many genes. PCC6912 showed, on the contrary, different transcriptional responses to each light condition and activated the FaRLiP response under the M-dwarf simulated light. Surprisingly, the anoxic atmosphere did not impact the transcriptional profile of the 2 strains significantly. Results show that both cyanobacteria seem inherently prepared for anoxia and to harvest the photons emitted by a simulated M-dwarf star, whether they are only visible (PCC6803) or also far-red photons (PCC6912). They also show that visible photons in the simulated M-dwarf are sufficient to keep a similar metabolism with respect to solar-simulated light.ConclusionResults prove the adaptability of the cyanobacterial metabolism and enhance the plausibility of finding oxygenic biospheres on exoplanets orbiting M-dwarf stars

Metodología experimental aplicada a la Inmunología Molecular

El objetivo general del proyecto es aplicar un modelo pedagógico en el que participen los alumnos de manera activa y apliquen el método científico en base a los conocimientos que han adquirido, resolviendo y realizando un caso práctico en el laboratorio. Integra una estrategia didáctica que va a fomentar la participación activa del alumnado provocando un aprendizaje significativo, ya que el alumno tiene que resolver mediante el razonamiento un caso práctico y luego integrarlo en el laboratorio con el uso de una técnica ampliamente utilizada en Inmunología, como es la citometría de flujo.Depto. de Arquitectura de Computadores y AutomáticaFac. de InformáticaFALSEInnovasubmitte

Multiple Scenario Generation of Subsurface Models:Consistent Integration of Information from Geophysical and Geological Data throuh Combination of Probabilistic Inverse Problem Theory and Geostatistics

Neutrinos with energies above 1017 eV are detectable with the Surface Detector Array of the Pierre Auger Observatory. The identification is efficiently performed for neutrinos of all flavors interacting in the atmosphere at large zenith angles, as well as for Earth-skimming \u3c4 neutrinos with nearly tangential trajectories relative to the Earth. No neutrino candidates were found in 3c 14.7 years of data taken up to 31 August 2018. This leads to restrictive upper bounds on their flux. The 90% C.L. single-flavor limit to the diffuse flux of ultra-high-energy neutrinos with an E\u3bd-2 spectrum in the energy range 1.0 7 1017 eV -2.5 7 1019 eV is E2 dN\u3bd/dE\u3bd &lt; 4.4 7 10-9 GeV cm-2 s-1 sr-1, placing strong constraints on several models of neutrino production at EeV energies and on the properties of the sources of ultra-high-energy cosmic rays

Hereditary connective tissue disorders: novel genotype-phenotype correlations, disease-genes and pathogenetic factors affecting disability

Hereditary soft connective tissue disorders (HCTDs)are a group of clinically variable and genetically heterogeneous conditions caused by constitutional abnormalities of the various components of the extracellular matrix (ECM). Although singularly rare, this community of syndromes are an emerging clinical phenomenon commonly encountered in different specialized settings, including but not limited to rheumatology, physical medicine, cardiology/heart surgery, and clinical genetics. EDS is probably the most common reason of referral in outpatient services dedicated to HCTDs. The 2017 international classification identifies 13 different clinical EDS forms due to mutations in no less than 19 genes. Nevertheless, probably no more than 20% of the patients who have a clinical diagnosis of EDS receive a molecular confirmation by the identification of the responsible mutation. On the other hand, EDS shares many features with the other HCTDs, and such a clinical similarity likely mirrors a common pathogenesis, at least, in specific cases. Therefore, it is expected that novel genes and novel genotype-phenotype correlations for known genes will be identified for EDS. Understanding the biological variability underpinning such a clinical variability is of utmost importance for seeking a tailored approach in the management of these patients. San Camillo-Forlanini Hospital (SCFH) is the Coordinator of the Regional (Lazio, Italy) reference centers for EDS and full member of the European Reference Network (ERN) for rare musculoskeletal diseases (ReCONNET). Since 2010, more than 800 patients who were referred to SCFH, received a diagnosis of EDS and were put under periodic medical follow-up. The aims of this PhD project were: 1) to highlight new genotype-phenotype correlations in HCTDs; 2) to identify novel disease genes for EDS-like phenotypes; 3) to explore disability determinants in a EDS patient cohort. In this context, for the years 2017-2019, the results of the current PhD project included (i) the discovery of the molecular cause of the exceptionally rare X-linked EDS variant, which resulted mutated in FLNA; (ii) the identification of TAB2 and MAP3K7, two genes encoding components of the non-canonic TGFβ-pathway, as responsible of phenotypes resembling EDS; (iii) characterization of musculoskeletal phenotype of hypermobile EDS, the most common EDS variant; (iv) characterization of the skin phenotype of classical EDS, the second most common EDS variant; (v) the exploration of the neurodevelopmental attributes of joint hypermobility in children with different forms of EDS and adults with hEDS in order to open the path for the identification of severity scoring in these disorders; (vi) the delineation of a severity scoring for adults with hypermobile EDS and HSD (hEDS/HSD); (vii) the clinical and molecular characterization of osteogenesis imperfecta/EDS overlap (OI/EDS); and (viii) the exploration of cellular effects of the mutations identified in TAB2 and MAP3K7. The related research activity resulted in 15 publications and SCFH was also represented in the International committee who published the current classification on EDS. The project has been nurtured by a multispecialistic team, aimed at exploring the biological and clinical variability of HCTDs with a true translational intent