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More than 50% of solar-mass stars form in multiple systems. It is therefore crucial to investigate how multiplicity affects the star and planet formation processes at the protostellar stage. We report continuum and C$^{18}$O (2-1) observations of the VLA 1623-2417 protostellar system at 50 au angular resolution as part of the ALMA Large Program FAUST. The 1.3 mm continuum probes the disks of VLA 1623A, B, and W, and the circumbinary disk of the A1+A2 binary. The C$^{18}$O emission reveals, for the first time, the gas in the disk-envelope of VLA 1623W. We estimate the dynamical mass of VLA 1623W, $M_{\rm dyn}=0.45\pm0.08$ M$_{\odot}$, and the mass of its disk, $M_{\rm disk}\sim6\times10^{-3}$ M$_{\odot}$. C$^{18}$O also reveals streamers that extend up to 1000 au, spatially and kinematically connecting the envelope and outflow cavities of the A1+A2+B system with the disk of VLA 1623W. The presence of the streamers, as well as the spatial ($\sim$1300 au) and velocity ($\sim$2.2 km/s) offset of VLA 1623W suggest that either sources W and A+B formed in different cores, interacting between them, or that source W has been ejected from the VLA 1623 multiple system during its formation. In the latter case, the streamers may funnel material from the envelope and cavities of VLA 1623AB onto VLA 1623W, thus concurring to set its final mass and chemical content., Comment: 10 pages, 5 figures, accepted by MNRAS

BackgroundEndovascular stents and flow diverters have become widely used for the treatment of vascular diseases; however, their effectiveness is often limited by the deposition and activation of blood platelets and leukocytes. The foreignness of these devices often triggers pathologic local reactions that impede their integration and compromise their efficacy. In this study, we developed a method to camouflage endovascular stents and flow diverters by coating them with a surface that mimics healthy endothelium, in order to promote more effective device integration and prevent the activation of blood cells.MethodsWe designed peptides using domain 1 and/or domain 2 of human CD31 and synthesized the chosen peptide to coat clinical-grade nitinol flow diverters and cobalt chromium balloon expandable stents. The coated stents were implanted in adult rabbits and included control groups of uncoated devices and drug-eluting CoCr stents. The rabbits were monitored for 60 days, during which we assessed the integration of the devices under a physiologic confluence of endothelial cells.ResultsOur results demonstrated that the stents coated with the CD31-Domain 1 mimicking peptide promoted a smooth integration of the devices under a physiologic confluence of endothelial cells. By day 7, the coated stents were entirely covered by a smooth endothelium, unlike bare-metal and drug-eluting stents which remained largely exposed to the flowing blood. By day 60, the coated stents demonstrated superiority over both bare-metal and drug-eluting stents, as they resulted in the formation of a “neo-arterial” wall at the entrance of the aneurysmal sac.ConclusionOur method provides a promising step towards the development of more effective and biocompatible endovascular devices. The CD31 domain 1 coating prevented the pathologic local reaction at the site of stent implantation and promoted faster and more effective device integration. Further studies are necessary to investigate the efficacy and safety of CD31 domain 1 coatings on a larger scale, as well as their long-term durability and potential clinical applications.

The aggregation properties of Semaglutide, a lipidated peptide drug agonist of the Glucagon-like peptide 1 receptor recently approved for treatment of diabetes type 2, have been investigated by spectroscopic techniques (UV-Vis absorption, steadystate and time-resolved fluorescence, electronic circular dichroism) and Molecular Dynamics simulations. We show that in the micromolar concentration region, in aqueous solution, Semaglutide is present as monomeric and dimeric species, with a characteristic monomer-to-dimer transition occurring at around 20 μM. The lipid chain stabilizes a globular morphology of the monomer and dimer species, giving rise to a locally well-defined polar outer surface where the lipid and peptide portions are packed to each other. At very long times, these peptide clusters nucleate the growth of larger aggregates characterized by a blue luminescence and a β-sheet arrangement of the peptide chains. The understanding of the oligomerization and aggregation potential of peptide candidates is key for the development of long acting and stable drugs

PDF file - 4.5MB, Figure S1. HMGB1 inhibitors hinder asbestos-induced HM transformation. Figure S2. Expressions of the HMGB1 receptors TLR2 and TLR4 are variable in MM cells. Figure S3. HMGB1 is a chemotactic and mitogenic factor in MM cells. Figure S4. Secreted HMGB1 is an autocrine chemotactic factor in MM cells. Figure S5. HMGB1 inhibition has no effect on the survival and migration of MM cells that are low HMGB1 producers (PPM-Mill). Figure S6. HMGB1 inhibition does not induce cell death in HM. Figure S7. Inhibition of HMGB1 induces apoptosis in MM cells "addicted" to HMGB1. Figure S8. HMGB1 supports the invasive phenotype in MM cells. Figure S9. Gene expression analysis of REN cells treated with HMGB1.

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Context. Protostellar jets are an important agent of star formation feedback, tightly connected with the mass-accretion process. The history of jet formation and mass ejection provides constraints on the mass accretion history and on the nature of the driving source. Aims. We characterize the time-variability of the mass-ejection phenomena at work in the class 0 protostellar phase in order to better understand the dynamics of the outflowing gas and bring more constraints on the origin of the jet chemical composition and the mass accretion history. Methods. Using the NOrthern Extended Millimeter Array (NOEMA) interferometer, we have observed the emission of the CO 2–1 and SO NJ = 54–43 rotational transitions at an angular resolution of 1.0 00 (820 au) and 0.400 (330 au), respectively, toward the intermediate mass class 0 protostellar system Cep E. Results. The CO high-velocity jet emission reveals a central component of ≤400 au diameter associated with high-velocity molecular knots that is also detected in SO, surrounded by a collimated layer of entrained gas. The gas layer appears to be accelerated along the main axis over a length scale δ0 ∼ 700 au, while its diameter gradually increases up to several 1000 au at 2000 au from the protostar. The jet is fragmented into 18 knots of mass ∼10−3 M, unevenly distributed between the northern and southern lobes, with velocity variations up to 15 km s−1 close to the protostar. This is well below the jet terminal velocities in the northern (+65 km s−1) and southern (-125 km s-1)lobes. The knot interval distribution is approximately bimodal on a timescale of ∼50–80 yr, which is close to the jet driving protostar Cep E-A and ∼150−20 yr at larger distances >1200. The mass-loss rates derived from knot masses are steady overall, with values of 2.7 x 10−5 M yr−1 and 8.9 x 10−6 M yr−1 in the northern and southern lobe, respectively. Conclusions. The interaction of the ambient protostellar material with high-velocity knots drives the formation of a molecular layer around the jet. This accounts for the higher mass-loss rate in the northern lobe. The jet dynamics are well accounted for by a simple precession model with a period of 2000 yr and a mass-ejection period of 55 yr. © Authors 2022 741002; National Science Foundation, NSF: AST-2102405; Horizon 2020 Framework Programme, H2020; H2020 Marie Skłodowska-Curie Actions, MSCA: 811312; European Research Council, ERC; Ministry of Education and Science of the Russian Federation, Minobrnauka: FEUZ-2020-0038; Centre National de la Recherche Scientifique, CNRS; Ural Federal University, UrFU interferometer. IRAM is supported by INSU/CNRS (France), MPG (Germany) and IGN (Spain). AS, BL, PR-RO, acknowledge support from the European Union’s Horizon 2020 research and innovation program under the Marie Skłodowska-Curie grant agreement No 811312 for the project “Astro-Chemical Origins” (ACO) and the European Research Council (ERC) under the European Union’s Horizon 2020 research and innovation program for the Project “The Dawn of Organic Chemistry” (DOC) grant agreement No 741002. DSC is supported by an NSF Astronomy and Astrophysics Postdoctoral Fellowship under award AST-2102405. A.V. and A.P. are the members of the Max Planck Partner Group at the Ural Federal University. A.P. and A.V. acknowledge the support of the Russian Ministry of Science and Education via the State Assignment Contract no. FEUZ-2020-0038. Based on observations carried out with the IRAM NOEMA interferometer. IRAM is supported by INSU/CNRS (France), MPG (Germany) and IGN (Spain). AS, BL, PR-RO, acknowledge support from the European Union’s Horizon 2020 research and innovation program under the Marie Skłodowska-Curie grant agreement No 811312 for the project "Astro-Chemical Origins" (ACO) and the European Research Council (ERC) under the European Union’s Horizon 2020 research and innovation program for the Project "The Dawn of Organic Chemistry" (DOC) grant agreement No 741002. DSC is supported by an NSF Astronomy and Astrophysics Postdoctoral Fellowship under award AST-2102405. A.V. and A.P. are the members of the Max Planck Partner Group at the Ural Federal University. A.P. and A.V. acknowledge the support of the Russian Ministry of Science and Education via the State Assignment Contract no. FEUZ-2020-0038.

Background Vedolizumab (VDZ) is commonly used as an off-label therapy in children with ulcerative colitis (UC) but no predictive factors of response are available. Vedolizumab binds α4β7 integrin and blocks the migration of T-lymphocytes and other cells, including eosinophils, which are involved in the UC inflammatory process. The aim of our study was to explore the predictive value of pre-therapy mucosal eosinophil count on the response to vedolizumab induction therapy in a paediatric population with UC Methods This is a retrospective, monocentric study, including children with UC treated with VDZ in the Paediatric Gastroenterology Unit of Policlinico Umberto I Hospital – Sapienza University of Rome. Histopathological data were analyzed for eosinophil counts in high power fields (hpf) in the cecum, transverse colon, sigma, and rectum prior to VDZ treatment. Clinical remission and response were evaluated at week 14 based on the PUCAI score. Results Twenty-five UC patients treated with VDZ were enrolled. All patients had failed previous anti-TNF therapy. Median baseline eosinophil count was 21 eo/hpf (5-60) in the cecum, 20 eo/hpf (6-68) in transverse colon, 44 eo/hpf (12-77) in sigma and 31 eo/hpf (9-67) in rectum. Baseline median eosinophil mucosal count in sigma was significantly higher in patients in remission (51[30-82]/ vs. 19[8.5–46] eosinophils/hpf, P23 eosinophils/hpf, with a sensitivity of 85.7% and specificity of 66.7% (Youden’s index 0.83) with an area under the curve (AUC) of 0.778 Conclusion Mucosal eosinophil abundance in sigma may predict remission to vedolizumab induction in paediatric UC. More studies are warranted to confirm these preliminary results and further investigate the role of mucosal eosinophils as a marker of therapeutic response and in the pathogenesis of UC

C. Codella et al., The ALMA (Atacama Large Millimeter Array) interferometer, with its unprecedented combination of high sensitivity and high angular resolution, allows for (sub-)mm wavelength mapping of protostellar systems at Solar system scales. Astrochemistry has benefitted from imaging interstellar complex organic molecules in these jet–disc systems. Here, we report the first detection of methanol (CH3OH) and methyl formate (HCOOCH3) emission towards the triple protostellar system VLA1623−2417 A1+A2+B, obtained in the context of the ALMA Large Programme FAUST (Fifty AU STudy of the chemistry in the disc/envelope system of solar-like protostars). Compact methanol emission is detected in lines from Eu = 45 K up to 61 K and 537 K towards components A1 and B, respectively. Large velocity gradient analysis of the CH3OH lines towards VLA1623−2417 B indicates a size of 0.11–0.34 arcsec (14–45 au), a column density NCH3OH = 1016–1017 cm−2, kinetic temperature ≥ 170 K, and volume density ≥ 108 cm−3. A local thermodynamic equilibrium approach is used for VLA1623−2417 A1, given the limited Eu range, and yields Trot ≤ 135 K. The methanol emission around both VLA1623−2417 A1 and B shows velocity gradients along the main axis of each disc. Although the axial geometry of the two discs is similar, the observed velocity gradients are reversed. The CH3OH spectra from B show two broad (4–5 km s−1) peaks, which are red- and blueshifted by ∼ 6–7 km s−1 from the systemic velocity. Assuming a chemically enriched ring within the accretion disc, close to the centrifugal barrier, its radius is calculated to be 33 au. The methanol spectra towards A1 are somewhat narrower (∼ 4 km s−1), implying a radius of 12–24 au., This project has received funding from: (1) the European Research Council (ERC) under the European Union’s Horizon 2020 research and innovation programme, for the Project ‘The Dawn of Organic Chemistry’ (DOC), grant agreement no. 741002; (2) the PRIN-INAF 2016 The Cradle of Life – GENESIS-SKA (General Conditions in Early Planetary Systems for the rise of life with SKA); (3) a Grant-in-Aid from Japan Society for the Promotion of Sci- ence (KAKENHI: Nos. 18H05222, 20H05844, 20H05845); (4) the Spanish FEDER under project number ESP2017-86582-C4-1-R; (5) DGAPA, UNAM grants IN112417 and IN112820, and CONACyT, Mexico; (6) ANR of France under contract number ANR-16-CE31- 0013; (7) the French National Research Agency in the framework of the Investissements d’Avenir programme (ANR-15-IDEX-02), through the funding of the ‘Origin of Life’ project of the Univ. Grenoble-Alpes, (8) the European Union’s Horizon 2020 research and innovation programmes under projects ‘Astro-Chemistry Ori- gins’ (ACO), Grant No. 811312; (9) the National Research Council Canada and an NSERC Dico v ery Grant to DJ. This paper makes use of the following ALMA data: ADS/JAO.ALMA#2018.1.01205.L. ALMA is a partnership of ESO (representing its member states), NSF (USA) and NINS (Japan), together with NRC (Canada), MOST and ASIAA (Taiwan), and KASI (Republic of Korea), in cooperation with the Republic of Chile. The Joint ALMA Obser- vatory is operated by ESO, A UI/NRA O, and NAOJ. The National Radio Astronomy Observatory is a facility of the National Science Foundation operated under cooperative agreement by Associated Universities, Inc.

El Macizo del Deseado es un distrito geológico que presenta una alta disponibilidad de materias primas de excelentecalidad para la talla. En nuestra área de estudio, en el extremo sur del Macizo, las formaciones Baqueró y Bajo Grandepresentan fuentes primarias y secundarias de madera silicificada, pero de distribución acotada y escasa visibilidad.Diversos estudios en el área mostraron la existencia de variabilidad respecto de las características macroscópicas, elgrado de silicificación y la localización de la madera silicificada. Las primeras evidencias de utilización de esta materiaprima se registran hacia el 8000 A.P., en un sector del espacio en que se encuentra inmediatamente disponible, sibien las primeras ocupaciones humanas datan de la transición Pleistoceno-Holoceno. En este trabajo se presentael análisis de una de estas fuentes primarias con el objetivo de evaluar si las características particulares de estamateria prima condicionaron de alguna manera su aprovechamiento por parte de los grupos cazadores recolectores. The Deseado Massif is a geological district that presents a high availability of excellent knapping quality raw materials. In our study area, at the Southern end of the Massif, the Baqueró and Bajo Grande Formations, present primary and secondary sources of silicified wood, but with a limited distribution and poor visibility. Several studies in the area showed the existence of variability with respect to the macroscopic characteristics, degree of silicification and location of the silicified woods. The first evidence of the use of this raw material is recorded around 8000 B.P., in a space where it is immediately available, although the first human occupations of the area date from the PleistoceneHolocene transition. This paper presents the analysis of one of these primary sources with the aim of evaluating if the particular characteristics of this raw material conditioned in some way its use by the hunter-gatherer groups Fil: Vetrisano, Lucas Javier. Consejo Nacional de Investigaciones Científicas y Técnicas. Oficina de Coordinación Administrativa Saavedra 15. Instituto Multidisciplinario de Historia y Ciencias Humanas; Argentina Fil: Franco, Nora Viviana. Consejo Nacional de Investigaciones Científicas y Técnicas. Oficina de Coordinación Administrativa Saavedra 15. Instituto Multidisciplinario de Historia y Ciencias Humanas; Argentina Fil: Bianchi, Pablo Emiliano. Consejo Nacional de Investigaciones Científicas y Técnicas. Oficina de Coordinación Administrativa Saavedra 15. Instituto Multidisciplinario de Historia y Ciencias Humanas; Argentina

C. Vastel et al., [Aims] Methanol is a ubiquitous species commonly found in the molecular interstellar medium. It is also a crucial seed species for the build-up of chemical complexity in star forming regions. Thus, understanding how its abundance evolves during the star formation process and whether it enriches the emerging planetary system is of paramount importance., [Methods] We used new data from the ALMA Large Program FAUST (Fifty AU STudy of the chemistry in the disc/envelope system of solar protostars) to study the methanol line emission towards the [BHB2007] 11 protobinary system (sources A and B), where a complex structure of filaments connecting the two sources with a larger circumbinary disc has previously been detected., [Results] Twelve methanol lines have been detected with upper energies in the [45–537] K range along with one 13CH3OH transition and one methyl formate (CH3OCHO) line blended with one of the methanol transitions. The methanol emission is compact (FWHM ~ 0.5″) and encompasses both protostars, which are separated by only 0.2″ (28 au). In addition, the overall methanol line emission presents three velocity components, which are not spatially resolved by our observations. Nonetheless, a detailed analysis of the spatial origin of these three components suggests that they are associated with three different spatial regions, with two of them close to 11B and the third one associated with 11A. A radiative transfer analysis of the methanol lines gives a kinetic temperature of [100–140] K, an H2 volume density of 106–107 cm−3 and column density of a few 1018 cm−2 in all three components with a source size of ~0.15″. Thus, this hot and dense gas is highly enriched in methanol with an abundance as high as 10−5. Using previous continuum data, we show that dust opacity can potentially completely absorb the methanol line emission from the two binary objects., [Conclusions] Although we cannot firmly exclude other possibilities, we suggest that the detected hot methanol is resulting from the shocked gas from the incoming filaments streaming towards [BHB2007] 11A and B, respectively. Higher spatial resolution observations are necessary to confirm this hypothesis., This project has received funding within the European Union’s Horizon 2020 research and innovation program from the European Research Council (ERC) for the project The Dawn of Organic Chemistry (DOC), grant agreement no. 741002, and from the Marie Sklodowska-Curie for the project Astro-Chemical Origins (ACO), grant agreement no. 811312. I.J.-S. has received partial support from the Spanish State Research Agency (project number PID2019-105552RB-C41). D.J. is supported by NRC Canada and by an NSERC Discovery Grant. S.Y. thanks the support by Grant-in-Aids from Ministry of Education, Culture, Sports, Science, and Technologies of Japan (18H05222). This paper makes use of the following ALMA data: ADS/JAO.ALMA#2018.1.01205.L. ALMA is a partnership of ESO (representing its member states), NSF (USA) and NINS (Japan), together with NRC (Canada), MOST and ASIAA (Taiwan), and KASI (Republic of Korea), in cooperation with the Republic of Chile. The Joint ALMA Observatory is operated by ESO, AUI/NRAO and NAOJ. The National Radio Astronomy Observatory is a facility of the National Science Foundation operated under cooperative agreement by Associated Universities, Inc.

Resumo Fundamento O pterostilbeno (PS), um composto polifenólico natural e antioxidante, surge como uma intervenção promissora para minimizar danos do infarto agudo do miocárdio (IAM). Objetivo Este estudo teve como objetivo avaliar o desempenho do PS na promoção da homeostase redox nos pulmões e no ventrículo direito (VD) de animais infartados. Métodos Ratos Wistar machos (60 dias de idade) foram randomizados em três grupos: SHAM, IAM (infarto) e IAM+PS (IAM + pterostilbeno). Sete dias após o procedimento de IAM, os ratos foram tratados com PS (100 mg/kg/dia) por gavagem por oito dias. Os animais foram depois sacrificados e os pulmões e VD foram coletados para análise do balanço redox (diferenças foram consideradas significativas quando p

Commonly, numerical weather model (NWM) users can get the vertically integrated water vapor (IWV) value at a given location from the values at nearby grid points. In this study we used a validated and freely available global navigation satellite system (GNSS) IWV data set to analyze the very well-known effect of height differences. To this end, we studied the behavior of 67 GNSS stations in Central and South America with the prerequisite that they have a minimum of 5 years of data during the period from 2007 to 2013. The values of IWV from GNSS were compared with the respective values from ERA-Interim and MERRA-2 from the same period. Firstly, the total set of stations was compared in order to detect cases in which the geopotential difference between GNSS and NWM required correction. An additive integral correction to the IWV values from ERA-Interim was then proposed. For the calculation of this correction, the multilevel values of specific humidity and temperature given at 37 pressure levels by ERA-Interim were used. The performance of the numerical integration method was tested by accurately reproducing the IWV values at every individual grid point surrounding each of the GNSS sites under study. Finally, considering the IWVGNSS values as a reference, the improvement introduced to the IWVERA-Interim values after correction was analyzed. In general, the corrections were always recommended, but they are not advisable in marine coastal areas or on islands as at least two grid points of the model are usually in the water. In such cases, the additive correction could overestimate the IWV.

Context. Hot corinos are compact regions around solar-mass protostellar objects that are very rich in interstellar Complex Organic Molecules (iCOMs). How the abundance of these molecules is affected by the environmental physical conditions is still an open question. More specifically, addressing this point is key to understand our own chemical origins since the Solar System formed in a large cluster of low- to high-mass stars and was therefore subject to external heating and ultraviolet irradiation which may have shaped the chemistry of its early formation stages. Aims. The goal of this high resolution study is to determine the abundance ratios of iCOMs in HOPS-108, which is a Class 0 protostar and a hot corino candidate located in the nearest Solar System analogue, the protostellar cluster OMC-2 FIR 4, in Orion. We aim to compare the abundance ratios to those found in other hot corinos, which are all located in less crowded environments, in order to understand the impact of environmental conditions on hot corinos’ chemistry. Methods. We observed the OMC-2 FIR 4 proto-cluster using the Band 6 of the Atacama Large (sub-)Millimetre Array in Cycle 4 with an angular resolution of ~0.′′28 (110 au). We determined the abundances and temperature of the species using local thermodynamic equilibrium (LTE) and non-LTE analysis. Results. Our results reveal a rich organic chemistry towards HOPS-108, asserting that it is a hot corino where the following iCOMs are detected: CH3OH, HCOOCH3, CH3OCH3, CH318OH, CH2DOH, CH3COCH3, CH3CHO, CH3CN, 13CH3CN, C2H5CN, and NH2CHO. Remarkably, we find a possible enhancement in the HCOOCH3 abundance with respect to other known hot corinos. Indeed, the [CH3OCH3]/[HCOOCH3] abundance ratio in this source is ~0.2 and, within the uncertainties, it deviates from the known correlation marginally where [CH3OCH3]/[HCOOCH3] ~1. A relatively low [CH2DOH]/[CH3OH] abundance ratio of ~0.02 is also obtained, which is in agreement with that found in another Orion source, HH212, suggesting a higher gas temperature during the early phases of ice mantle formation. Conclusions. The [CH3OCH3]/[HCOOCH3] and [CH2DOH]/[CH3OH] abundance ratios in HOPS-108 might result from different physical conditions in the Orion molecular complex compared to other regions. The former ratio cannot be reproduced with current chemical models, highlighting the importance of improving the chemical networks with theoretical calculations. More hot corinos located in heavily clustered regions such as Orion should be targeted in order to measure these ratios and evaluate whether they are an environmental product or whether HOPS-108 is an exceptional hot corino overall.

We present new data concerning lichen species of the Italian flora and confirm 36 national redlisted species.

DNA damage is increased in Alzheimer’s disease (AD), while the underlying mechanisms are unknown. Here, we employ comprehensive phosphoproteome analysis, and identify abnormal phosphorylation of 70 kDa subunit of Ku antigen (Ku70) at Ser77/78, which prevents Ku70-DNA interaction, in human AD postmortem brains. The abnormal phosphorylation inhibits accumulation of Ku70 to the foci of DNA double strand break (DSB), impairs DNA damage repair and eventually causes transcriptional repression-induced atypical cell death (TRIAD). Cells under TRIAD necrosis reveal senescence phenotypes. Extracellular high mobility group box 1 (HMGB1) protein, which is released from necrotic or hyper-activated neurons in AD, binds to toll-like receptor 4 (TLR4) of neighboring neurons, and activates protein kinase C alpha (PKCα) that executes Ku70 phosphorylation at Ser77/78. Administration of human monoclonal anti-HMGB1 antibody to post-symptomatic AD model mice decreases neuronal DSBs, suppresses secondary TRIAD necrosis of neurons, prevents escalation of neurodegeneration, and ameliorates cognitive symptoms. TRIAD shares multiple features with senescence. These results discover the HMGB1-Ku70 axis that accounts for the increase of neuronal DNA damage and secondary enhancement of TRIAD, the cell death phenotype of senescence, in AD., Tanaka et al use phosphoproteome analysis of post-mortem Alzheimer’s Disease (AD) brains and identified abnormal phosphorylation of Ku70, which leads to DNA damage and transcriptional repression-induced atypical cell death. In a mouse model of AD, the authors show that Ku70 phosporylation is regulated by extracellular high mobility group box 1 protein, thus shedding light on the mechanism of DNA damage in AD.

We describe the AMBITION project, a mission to return the first-ever cryogenically-stored sample of a cometary nucleus, that has been proposed for the ESA Science Programme Voyage 2050. Comets are the leftover building blocks of giant planet cores and other planetary bodies, and fingerprints of Solar System’s formation processes. We summarise some of the most important questions still open in cometary science and Solar System formation after the successful Rosetta mission. We show that many of these scientific questions require sample analysis using techniques that are only possible in laboratories on Earth. We summarize measurements, instrumentation and mission scenarios that can address these questions. We emphasize the need for returning a sample collected at depth or, still more challenging, at cryogenic temperatures while preserving the stratigraphy of the comet nucleus surface layers. We provide requirements for the next generation of landers, for cryogenic sample acquisition and storage during the return to Earth. Rendezvous missions to the main belt comets and Centaurs, expanding our knowledge by exploring new classes of comets, are also discussed. The AMBITION project is discussed in the international context of comet and asteroid space exploration.

Background Host inflammation contributes to determine whether SARS-CoV-2 infection causes mild or life-threatening disease. Tools are needed for early risk assessment. Methods We studied in 111 COVID-19 patients prospectively followed at a single reference Hospital fifty-three potential biomarkers including alarmins, cytokines, adipocytokines and growth factors, humoral innate immune and neuroendocrine molecules and regulators of iron metabolism. Biomarkers at hospital admission together with age, degree of hypoxia, neutrophil to lymphocyte ratio (NLR), lactate dehydrogenase (LDH), C-reactive protein (CRP) and creatinine were analysed within a data-driven approach to classify patients with respect to survival and ICU outcomes. Classification and regression tree (CART) models were used to identify prognostic biomarkers. Results Among the fifty-three potential biomarkers, the classification tree analysis selected CXCL10 at hospital admission, in combination with NLR and time from onset, as the best predictor of ICU transfer (AUC [95% CI] = 0.8374 [0.6233–0.8435]), while it was selected alone to predict death (AUC [95% CI] = 0.7334 [0.7547–0.9201]). CXCL10 concentration abated in COVID-19 survivors after healing and discharge from the hospital. Conclusions CXCL10 results from a data-driven analysis, that accounts for presence of confounding factors, as the most robust predictive biomarker of patient outcome in COVID-19. Graphic abstract

Glioblastoma is the most common primary malignant brain tumor. Despite treatments combining excisional surgery, chemotherapy, and radiotherapy, overall survival remains low and the incidence of tumor recurrence remains high. Advances in the understanding of the disease, particularly its molecular biology and the mechanisms of action of systemic and radiotherapeutic treatments, as well as the development of image-guided surgical techniques, offer hope for the control of this hitherto incurable disease.Le glioblastome est la tumeur cérébrale maligne primitive la plus fréquente. Malgré des traitements combinant la chirurgie d’exérèse, la chimiothérapie et la radiothérapie, la survie globale reste faible avec une incidence élevée de récidive tumorale. Les progrès dans la compréhension de la maladie, et en particulier de la biologie moléculaire et des mécanismes d’action des traitements systémiques et radiothérapeutiques, de même que le développement des techniques chirurgicales guidées par l’image, permettent d’entrevoir un espoir dans le contrôle de cette maladie jusqu’ici incurable.

The latest developments in astrochemistry have shown how some molecular species can be used as a tool to study the early stages of the solar-type star formation process. Among them, the more relevant species are the interstellar complex organic molecules (iCOMs) and the deuterated molecules. Their analysis give us information on the present and past history of protostellar objects. Among the protostellar evolutionary stages, Class I protostars represent a perfect laboratory in which to study the initial conditions for the planet formation process. Indeed, from a physical point of view, the Class I stage is the bridge between the Class 0 phase, dominated by the accretion process, and the protoplanetary disk phase, when planets form. Despite their importance, few observations of Class I protostars exist and very little is known about their chemical content. In this paper we review the (few) existing observations of iCOMs and deuterated species in Class I protostars. In addition, we present new observations of deuterated cyanoacetylene and thioformaldehyde towards the Class I protostar SVS13-A. These new observations allow us to better understand the physical and chemical structure of SVS13-A and compare the cyanoacetylene and thioformaldehyde deuteration with other sources in different evolutionary phases., 51 pages, 10 figures

Context. Deuteration is a precious tool for investigating the origin and formation routes of interstellar complex organic molecules in the different stages of the star formation process. Methyl cyanide (CH3CN) is one of the most abundant interstellar complex organic molecules (iCOMs); it is of particular interest because it is among the very few iCOMs detected not only around protostars but also in protoplanetary disks. However, its formation pathways are not well known and only a few measurements of its deuterated isotopologue (CH2DCN) have been made to date. Aims. We studied the line emission from CH3CN and its deuterated isotopologue CH2DCN towards the prototypical Class I object SVS13-A, where the deuteration of a large number of species has already been reported. Our goal is to measure the CH3CN deuteration in a Class I protostar, for the first time, in order to constrain the CH3CN formation pathways and the chemical evolution from the early prestellar core and Class 0 to the evolved Class I stages. Methods. We imaged CH2DCN towards SVS13-A using the IRAM NOEMA interferometer at 3mm in the context of the Large Program SOLIS (with a spatial resolution of 1″.8 × 1″.2). The NOEMA images were complemented by the CH3CN and CH2DCN spectra collected by the IRAM-30m Large Program ASAI, which provided an unbiased spectral survey at 3 mm, 2 mm, and 1.3 mm. The observed line emission was analysed using local thermodynamic equilibrium (LTE) and non-LTE large velocity gradient (LVG) approaches. Results. The NOEMA/SOLIS images of CH2DCN show that this species emits in an unresolved area centred towards the SVS13-A continuum emission peak, suggesting that methyl cyanide and its isotopologues are associated with the hot corino of SVS13-A, previously imaged via other iCOMs. In addition, we detected 41 and 11 ASAI transitions of CH3CN and CH2DCN, respectively, which cover upper level energies (Eup) from 13 to 442 K and from 18 K to 200 K. The non-LTE LVG analysis of the CH3CN lines points to a kinetic temperature of (140 ± 20) K, a gas density nH2 ≥ 107 cm−3, and an emitting size of ~0″.3, in agreement with the hypothesis that CH3CN lines are emitted in the SVS13-A hot corino. The derived [CH2DCN]/[CH3CN] ratio is ~9%. This value is consistent with those measured towards prestellar cores and a factor 2–3 higher than those measured in Class 0 protostars. Conclusions. Contrarily to what expected for other molecular species, the CH3CN deuteration does not show a decrease in SVS13-A with respect to measurements in younger prestellar cores and Class 0 protostars. Finally, we discuss why our new results suggest that CH3CN was likely synthesised via gas-phase reactions and frozen onto the dust grain mantles during the cold prestellar phase.

The EndoLuminal Surgical System (ELS) is an emerging non-linear robotic system specifically designed for transanal surgery that allows for excision of colorectal neoplasia and luminal defect closure.An evaluation of ELS was conducted by a single surgeon in a preclinical setting at the EndoSurgical Center of Florida in Orlando, between October 1st, 2020 and December 31st, 2020, using porcine colon as a model. Mock lesions measured 2.5 to 3.5 cm were excised partial-thickness. Specimen quality and excision time was assessed and evaluated.Twenty consecutive robotic transanal minimally invasive surgery (TAMIS) operations utilizing the ELS system were successfully performed without fragmentation. The mean and standard deviation procedure time for all 20 cases was 18.41 ± 14.15 min. The latter 10 cases were completed in substantially less time, suggesting that ELS requires at least 10 preclinical cases for a surgeon to become familiar with the technology. A second task, namely suture closure of the partial-thickness defect, was performed in 9 of the 20 cases. Mean time and standard deviation for this task measured 27.89 ± 10.07 min. There were no adverse events.ELS was successful in performing the tasks of partial-thickness disc excision and closure in a preclinical evaluation. Further study is necessary to determine its clinical applicability.

We have observed the very low-mass Class 0 protostar IRAS 15398−3359 at scales ranging from 50 to 1800 au, as part of the Atacama Large Millimeter/Submillimeter Array Large Program FAUST. We uncover a linear feature, visible in H2CO, SO, and C18O line emission, which extends from the source in a direction almost perpendicular to the known active outflow. Molecular line emission from H2CO, SO, SiO, and CH3OH further reveals an arc-like structure connected to the outer end of the linear feature and separated from the protostar, IRAS 15398−3359, by 1200 au. The arc-like structure is blueshifted with respect to the systemic velocity. A velocity gradient of 1.2 km s−1 over 1200 au along the linear feature seen in the H2CO emission connects the protostar and the arc-like structure kinematically. SO, SiO, and CH3OH are known to trace shocks, and we interpret the arc-like structure as a relic shock region produced by an outflow previously launched by IRAS 15398−3359. The velocity gradient along the linear structure can be explained as relic outflow motion. The origins of the newly observed arc-like structure and extended linear feature are discussed in relation to turbulent motions within the protostellar core and episodic accretion events during the earliest stage of protostellar evolution. The authors thank the anonymous reviewer for invaluable comments. They are also grateful to Hauyu Baobab Liu for useful discussions. This paper makes use of the following ALMA data set: ADS/JAO.ALMA#2018.1.01205.L (PI: Satoshi Yamamoto). ALMA is a partnership of the ESO (representing its member states), the NSF (USA) and NINS (Japan), together with the NRC (Canada) and the NSC and ASIAA (Taiwan), in cooperation with the Republic of Chile. The Joint ALMA Observatory is operated by the ESO, the AUI/NRAO, and the NAOJ. The authors thank to the ALMA staff for their excellent support. This work is supported by the projects PRIN-INAF-MAIN-STREAM 2017 Protoplanetary disks seen through the eyes of new-generation instruments, ARIEL and the astrochemical link between circumstellar disks and planets, and the European Research Council (ERC) under the European Union's Horizon 2020 research and innovation programmes: The Dawn of Organic Chemistry (DOC), grant agreement No. 741002, and Astro-Chemistry Origins (ACO), grant No. 811312. The National Radio Astronomy Observatory is a facility of the National Science Foundation operated under cooperative agreement by Associated Universities, Inc. I.J.-S. has received partial support from the Spanish FEDER (project number ESP2017-86582-C4-1-R) and the State Research Agency (AEI; project number PID2019-105552RB-C41). D.J. is supported by NRC Canada and by an NSERC Discovery Grant. This project is also supported by a Grant-in-Aid from Japan Society for the Promotion of Science (KAKENHI: Nos. 18H05222, 19H05069, 19K14753). Yuki Okoda thanks the Advanced Leading Graduate Course for Photon Science (ALPS) and Japan Society for the Promotion of Science (JSPS) for financial support. Peerreview

Transcription factor dynamics is fundamental to determine the activation of accurate transcriptional programs and yet is heterogeneous at single-cell level, even between very similar cells. We asked how such heterogeneity emerges for the nuclear factorκB (NF-κB), whose dynamics have been reported to cover a wide spectrum of behaviors, including persistent, oscillatory and weak activation. We found that clonal populations of immortalized fibroblasts derived from a single mouse embryo (that can hence be considered quasi-identical) display robustly distinct dynamics upon tumor necrosis ɑ (TNF-ɑ) stimulation, which give rise to differences in the transcription of NF-κB targets. Notably, standard transcriptomic analyses indicate that the clones differ mostly in transcriptional programs related with development, but not in TNF-ɑ signaling. However, by combining transcriptomics data and simulations we show how the expression levels of genes coding for proteins of the signaling cascade determine the differences in early NF-κB activation; differences in the expression of IκBɑ determine differences in its persistence and oscillatory behavior. The same analysis predicts inter-clonal differences in the NF-κB response to IL-1β. We propose that small (less than twofold) differences at transcript level are a source of heterogeneity in TF dynamics within homogeneous cell populations, and all the more so among different cell types.Abstract Figure

The isotopic ratio of nitrogen presents a wide range of values in the Solar System and in star forming system whose origin is still unclear. Chemical reactions in the gas phase are one of the possible processes that could modify the $^{14}$N/$^{15}$N ratio. We aim at investigating if and how the passage of a shock wave in the interstellar medium, can affect the relative fraction of nitrogen isotopes. The ideal place for such a study is the L1157 outflow, where several shocked clumps are present. We present the first measurement of the $^{14}$N/$^{15}$N ratio in the two shocked clumps, B1 and B0, of the protostellar outflow L1157, derived from the interferomteric maps of the H$^{13}$CN(1-0) and the HC$^{15}$N(1-0) lines. In B1, we find that the H$^{13}$CN(1-0) and HC$^{15}$N(1-0) emission traces the front of the clump, with averaged column density of $N$(H$^{13}$CN) $\sim$ 7$\times$10$^{12}$ cm$^{-2}$ and $N$(HC$^{15}$N) $\sim$ 2$\times$10$^{12}$ cm$^{-2}$. In this region the ratio H$^{13}$CN(1-0)/HC$^{15}$N(1-0) is quite uniform with an average value of $\sim$ 5$\pm$1. The same average value is also measured in the smaller clump B0e. Assuming the standard $^{12}$C/$^{13}$C = 68, we obtain $^{14}$N/$^{15}$N = 340$\pm$70, similar to those usually found in prestellar cores and protostars. We analysed the prediction of a chemical shock model for several shock conditions and we found that the nitrogen and carbon fractionations do not vary much for the first period after the shock. The observed H$^{13}$CN/HC$^{15}$N can be reproduced by a non-dissociative, C-type shock with parameters in agreement with previous modelling of L1157-B1. Both observations and chemical models indicate that the shock propagation does not affect the nitrogen isotopic ratio that remains similar to that measured in lower temperature gas in prestellar cores and in protostellar envelopes., 7 pages, 6 figures

The Southern End of the Deseado Massif (SDM, Patagonia, Argentina) is part of a morphostructural region with seasonal shallow lakes and streams highly dependent on rainfall. The area is rich in rock shelters and both primary and secondary sources of high-quality siliceous rocks. To the South there are basaltic plateaus and open plains where no such sources have been identified. Although a relatively big space was explored, rock structures forming groups were located in only a small part of it. In this paper we seek to analyze the reasons for their location and the way in which they were used. In order to do this, we present information related to their frequency, characteristics, and the archaeological context recovered. In addition, in order to understand the way in which they were used, the visibility of nearby environments was analyzed with Geographical Information Systems, using a DEM (Digital Elevation Model) developed by the Argentine Instituto Geografico Nacional (IGN). Results obtained indicate that the rock structures were built in places higher than the surroundings, using immediately available rocks. According to the visibility analysis, they worked in an articulated way as part of collective hunting strategies. The characteristics and composition of the artifact assemblages recovered indicate that different activities took place at these sites during the Late Holocene. The identification of the hunting blinds in a specific area within the SDM and their absence in the remaining study area to the North and South suggest that this area was selected for planned collective hunting.

Context. Recent results in astrochemistry have revealed that some molecules, such as interstellar complex organic species and deuterated species, can serve as valuable tools in the investigation of star-forming regions. Sulphuretted species can also be used to follow the chemical evolution of the early stages of a Sun-like star formation process. Aims. The goal is to obtain a census of S-bearing species using interferometric images towards SVS13-A, a Class I object associated with a hot corino that is rich in interstellar complex organic molecules. Methods. To this end, we used the NGC 1333 SVS13-A data at 3 mm and 1.4 mm obtained with the IRAM-NOEMA interferometer in the framework of the SOLIS (Seeds of Life in Space) Large Program. The line emission of S-bearing species was imaged and analyzed using local thermodynamic equilibrium (LTE) and large velocity gradient (LVG) approaches. Results. We imaged the spatial distribution on ≤300 au scale of the line emission of 32SO, 34SO, C32S, C34S, C33S, OCS, H2C32S, H2C34S, and NS. The low excitation (9 K) 32SO line traces: (i) the low-velocity SVS13-A outflow and (ii) the fast (up to 100 km s−1 away from the systemic velocity) collimated jet driven by the nearby SVS13-B Class 0 object. Conversely, the rest of the lines are confined in the inner SVS13-A region, where complex organics were previously imaged. More specifically, the non-LTE LVG analysis of SO, SO2, and H2CS indicates a hot corino origin (size in the 60–120 au range). Temperatures between 50 K and 300 K, as well as volume densities larger than 105 cm−3 have been derived. The abundances of the sulphuretted are in the following ranges: 0.3–6 × 10−6 (CS), 7 × 10−9–1 × 10−7 (SO), 1–10 × 10−7 (SO2), a few 10−10 (H2CS and OCS), and 10−10–10−9 (NS). The N(NS)/N(NS+) ratio is larger than 10, supporting the assessment that the NS+ ion is mainly formed in the extended envelope. Conclusions. The [H2CS]/[H2CO] ratio, once measured at high-spatial resolutions, increases with time (from Class 0 to Class II objects) by more than one order of magnitude (from ≤10−2 to a few 10−1). This suggests that [S]/[O] changes along the process of Sun-like star formation. Finally, the estimate of the [S]/[H] budget in SVS13-A is 2–17% of the Solar System value (1.8 × 10−5), which is consistent with what was previously measured towards Class 0 objects (1–8%). This finding supports the notion that the enrichment of the sulphuretted species with respect to dark clouds remains constant from the Class 0 to the Class I stages of low-mass star formation. The present findings stress the importance of investigating the chemistry of star-forming regions using large observational surveys as well as sampling regions on the scale of the Solar System.

This article has been retracted. Please see the Retraction Notice for more detail: https://doi.org/10.1186/s10020-020-00264-1

Class I protostars are a bridge between Class 0 protostars, and Class II protoplanetary disks. Recent studies show gaps and rings in the dust distribution of disks younger than 1 Myr, suggesting that planet formation may start already at the Class I stage. To understand what chemistry planets will inherit, it is crucial to characterize the chemistry of Class I sources and to investigate how chemical complexity evolves from Class 0 protostars to protoplanetary disks. The goal is twofold: to obtain a census of the molecular complexity in a sample of four Class I protostars, and to compare it with the chemical compositions of earlier and later phases of the Sun-like star formation process. We performed IRAM-30m observations towards Class I objects (L1489-IRS, B5-IRS1, L1455-IRS1, and L1551-IRS5). The column densities of the detected species are derived assuming LTE or LVG. We detected 27 species: C-chains, N-bearing, S-bearing, Si-bearing species, deuterated molecules, and iCOMs. Different spectral profiles are observed: narrow lines towards all the sources, broader lines towards L1551-IRS5, and line wings due to outflows. Narrow c-C3H2 emission originates from the envelope. The iCOMs in L1551-IRS5 reveal the occurrence of hot corino chemistry, with CH3OH and CH3CN lines originating from a compact and warm region. Finally, OCS and H2S seem to probe the circumbinary disks in the L1455-IRS1 and L1551-IRS5 binary systems. The deuteration in terms of elemental D/H in the molecular envelopes and hot corino are derived. In addition, B5 IRS1, L1455-IRS1 and L1551-IRS5 show a low excitation methanol line, suggesting an origin from an extended structure, plausibly UV illuminated. The abundance ratios of iCOMs with respect CH3OH measured towards the L1551-IRS5 hot corino and the deuteration in our sample are comparable to that estimated at earlier stages, as well as to that found in comets., Comment: 43 pages, 19 figures, accepted by A&A

In questa sezione monografica di «Humanitas» abbiamo voluto analizzare forme ed espressioni di silenzio in vari contesti religiosi attraverso il tempo e lo spazio. Al centro del nostro interesse è quindi il silenzio nel religioso, un tema su cui esiste già una ricca letteratura, che tuttavia per la maggior parte ne indaga modalità, valenze e usi limitatamente a una specifica tradizione. Il contributo che speriamo di portare agli studi va cercato nella marcata mutidisciplinarità del progetto e nella trasversalità culturale dei contenuti trattati.

Planets form in protoplanetary disks and inherit their chemical composition. It is therefore crucial to understand the disks molecular content. We aim to characterize the distribution and abundance of molecules in the disk of DG Tau. In the context of the ALMA chemical survey of Disk-Outflow sources in Taurus (ALMA-DOT) we analyse ALMA observations of the disk of DG Tau in H2CO 3(1,2)-2(1,1), CS 5-4, and CN 2-1 at ~0.15", i.e. ~18 au at 121 pc. H2CO and CS originate from a disk ring at the edge of the 1.3mm dust continuum, with CS probing an outer disk region with respect to H2CO (peaking at ~70 and ~60 au, respectively). CN originates from an outermost disk/envelope region peaking at ~80 au. H2CO is dominated by disk emission, while CS probes also two streams of material possibly accreting onto the disk with a peak of emission where the stream connects to the disk. The ring- and disk-height- averaged column densities are ~2.4-8.6e13 cm-2 (H2CO), ~1.7-2.5e13 cm-2 (CS), and ~1.9-4.7e13 cm-2 (CN). Unsharp masking reveals a ring of enhanced dust emission at ~40 au, i.e. just outside the CO snowline (~30 au). CS and H2CO emissions are co-spatial suggesting that they are chemically linked. The observed rings of molecular emission at the edge of the 1.3mm continuum may be due to dust opacity effects and/or continnum over-subtraction in the inner disk; as well as to increased UV penetration and/or temperature inversion at the edge of the mm-dust which would cause an enhanced gas-phase formation and desorption of these molecules. Moreover, H2CO and CS originate from outside the ring of enhanced dust emission, which also coincides with a change of the linear polarization at 0.87mm. This suggests that outside the CO snowline there could be a change of the dust properties which would reflect in the increase of the intensity (and change of polarization) of continuum, and of molecular emission., 13 pages, accepted for publication on A&A