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Plant pathogens secrete proteins called effectors that target host cellular processes to promote disease. Recently, structural genomics has identified several families of fungal effectors that share a similar three-dimensional structure despite remarkably variable amino-acid sequences and surface properties. To explore the selective forces that underlie the sequence variability of structurally-analogous effectors, we focused on MAX effectors, a structural family of effectors that are major determinants of virulence in the rice blast fungusPyricularia oryzae. Using structure-informed gene annotation, we identified 58 to 78 MAX effector genes per genome in a set of 120 isolates representing seven host-associated lineages. The expression of MAX effector genes was primarily restricted to the early biotrophic phase of infection and strongly influenced by the host plant. Pangenome analyses of MAX effectors demonstrated extensive presence/absence polymorphism and identified gene loss events possibly involved in host range adaptation. However, gene knock-in experiments did not reveal a strong effect on virulence phenotypes suggesting that other evolutionary mechanisms are the main drivers of MAX effector losses. MAX effectors displayed high levels of standing variation and high rates of non-synonymous substitutions, pointing to widespread positive selection shaping the molecular diversity of MAX effectors. The combination of these analyses with structural data revealed that positive selection acts mostly on residues located in particular structural elements and at specific positions. Our work provides unique insights into the evolutionary history of an extended fungal effector family and opens up new research avenues to deepen our understanding of the molecular coevolutionary interactions of fungi with plant hosts.AUTHOR SUMMARYFungal plant pathogens use small secreted proteins, called effectors, to manipulate to their own advantage their host’s physiology and immunity. The evolution of these effectors, whether spontaneously or in response to human actions, can lead to epidemics or the emergence of new diseases. It is therefore crucial to understand the mechanisms underlying this evolution. In this article, we report on the evolution of effectors in one of the prime experimental model systems of plant pathology, the fungus causing blast diseases in rice, wheat, and other cereals or grasses. We identify a particular class of effectors, the MAX effectors, using structural models based on experimental protein structures of effectors previously shown to have a major role in fungal virulence. We show that this class of effector is produced by the pathogen during the early stages of infection, when plant cells are still alive. By comparing the gene content of isolates infecting different plant species, we show that the MAX effector arsenal is highly variable from one isolate to another. Finally, using the inferential framework of population genetics, we demonstrate that MAX effectors exhibit very high genetic variability and that this results from the action of natural selection.

The study of exoplanets and especially their atmospheres can reveal key insights on their evolution by identifying specific atmospheric species. For such atmospheric investigations, high-resolution transmission spectroscopy has shown great success, especially for Jupiter-type planets. Towards the atmospheric characterization of smaller planets, the super-Earth exoplanet 55 Cnc e is one of the most promising terrestrial exoplanets studied to date. Here, we present a high-resolution spectroscopic transit observation of this planet, acquired with the PEPSI instrument at the Large Binocular Telescope. Assuming the presence of Earth-like crust species on the surface of 55 Cnc e, from which a possible silicate-vapor atmosphere could have originated, we search in its transmission spectrum for absorption of various atomic and ionized species such as Fe , Fe+, Ca , Ca+, Mg and K , among others. Not finding absorption for any of the investigated species, we are able to set absorption limits with a median value of 1.9 x RP. In conclusion, we do not find evidence of a widely extended silicate envelope on this super-Earth reaching several planetary radii., Comment: MNRAS, in press

We exploit the increased sensitivity of the recently installed AO SOUL at the LBT to obtain new high-spatial-resolution NIR images of the massive young stellar object IRAS20126+4104 and its outflow. We aim to derive the jet proper motions and kinematics, as well as to study its photometric variability by combining the novel performances of SOUL together with previous NIR images. We used both broad-band ($K_{s}$, $K'$) and narrow-band (Br$\gamma$, H2) observations from a number of NIR cameras (UKIRT/UFTI,SUBARU/CIAO,TNG/NICS,LBT/PISCES,and LBT/LUCI1) to derive maps of the continuum and the H$_2$ emission in the 2.12 $\mu$m line. Three sets of images, obtained with AO systems (CIAO,2003; FLAO,2012; SOUL,2020), allowed us to derive the proper motions of a large number of H$_2$ knots along the jet. Photometry from all images was used to study the jet variability. We derived knot proper motions in the range of 1.7-20.3 mas yr$^{-1}$ (i.e. 13-158 km s$^{-1}$ at 1.64 kpc, avg. outflow tangential velocity $\sim$ 80 km s$^{-1}$). The derived knot dynamical age spans a $\sim$ 200-4000 yr interval. A ring-like H$_2$ feature near the protostar location exhibits peculiar kinematics and may represent the outcome of a wide-angle wind impinging on the outflow cavity. Both H$_2$ geometry and velocities agree with those inferred from proper motions of the H$_2$O masers, located at a smaller distance from the protostar. Although the total H$_2$ line emission from the knots does not exhibit time variations at a $\widetilde{>}$ 0.3 mag level, we have found a clear continuum flux variation (radiation scattered by the dust in the cavity opened by the jet) which is anti-correlated between the blue-shifted and red-shifted lobes and may be periodic (with a period of $\sim$ 12-18 yr). We suggest that the continuum variability might be related to inner-disc oscillations which have also caused the jet precession., Comment: 26 pages, 22 figures, 2 mpeg files, accepted by Astronomy & Astrophysics

With the global rise of human‐mediated translocations and invasions, it is critical to understand the genomic consequences of hybridization and mechanisms of range expansion. Conventional wisdom is that high genetic drift and loss of genetic diversity due to repeated founder effects will constrain introduced species. However, reduced genetic variation can be countered by behavioral aspects and admixture with other distinct populations. As planned invasions, classical biological control (biocontrol) agents present important opportunities to understand the mechanisms of establishment and spread in a novel environment. The ability of biocontrol agents to spread and adapt, and their effects on local ecosystems, depends on genomic variation and the consequences of admixture in novel environments. Here, we use a biocontrol system to examine the genome‐wide outcomes of introduction, spread, and hybridization in four cryptic species of a biocontrol agent, the tamarisk beetle (Diorhabda carinata, D. carinulata, D. elongata, and D. sublineata), introduced from six localities across Eurasia to control the invasive shrub tamarisk (Tamarix spp.) in western North America. We assembled a de novo draft reference genome and applied RADseq to over 500 individuals across laboratory cultures, the native ranges, and the introduced range. Despite evidence of a substantial genetic bottleneck among D. carinulata in N. America, populations continue to establish and spread, possibly due to aggregation behavior. We found that D. carinata, D. elongata, and D. sublineata hybridize in the field to varying extents, with D. carinata × D. sublineata hybrids being the most abundant. Genetic diversity was greater at sites with hybrids, highlighting potential for increased ability to adapt and expand. Our results demonstrate the complex patterns of genomic variation that can result from introduction of multiple ecotypes or species for biocontrol, and the importance of understanding them to predict and manage the effects of biocontrol agents in novel ecosystems.

Year-class strength of fish stocks is often set during the larval stage, with fast growth being a favourable factor leading to strong recruitment. Following 30 years of poor recruitment, redfish (Sebastes sp.) in the Gulf of St. Lawrence (GSL) produced unprecedentedly strong year classes in 2011–2013. The relationship between larval diet and growth that potentially drove these successful recruitment events is unknown. Gut content and otolith microstructure of redfish larvae collected from the GSL in 1999 and 2000 were analysed in order to understand the relationship between recent feeding success and growth in larval redfish, and identify feeding behaviours that are associated with fast growth. Growth was positively correlated with larval body depth (BD), which was used as a morphological proxy for growth. Prey type and size were the best explanatory variables of larval BD after obligatory first-feeding. Larvae that consumed large naupliar stages of frequently consumed copepod taxa were deeper-bodied and grew more quickly than larvae that consumed redfish's preferred prey, Calanus finmarchicus eggs. Warming GSL waters have shifted the phenology of commonly consumed prey taxa earlier in the season, which may increase the overlap between redfish and naupliar prey that drive fast growth, survival, and potentially recruitment success.

The microplastics (MPs) pollution has been widely documented in all type of aquatic environment. However, most of the studies focus on the MPs contamination in the surface water and there is a lack of knowledge about contamination in the water column. In the present study, we adapted an aquatic drone to sample MPs both in the water surface (0 – 25 cm) and subsurface (25-50 cm). In a previous study, the aquatic drone has been shown to be more accurate for sampling MPs than the Manta net. The samples of surface and subsurface water were collected in a river with the aquatic drone, while an in-situ pump was used to sample water near the bottom (2 to 3 m depth) of the river. MPs concentrations (n.L-1) and their characteristics (size, morphology, color, shape and polymer nature) were determined and compared between the three sampling compartments. All of the water compartments sampled were contaminated. Our results showed that subsurface water could be as contaminated as the surface water. In terms of shape, fibers and film were a majority on the water surface while fragments were found in greater proportion in subsurface water. This study demonstrates that sampling only the water surface could result in bias for assessing the MPs contamination in aquatic environment. Also see: https://micro2022.sciencesconf.org/426655/document, In MICRO 2022, Online Atlas Edition: Plastic Pollution from MACRO to nano

Resistance to potyviruses in plants have been largely provided by the selection of natural variant alleles of eukaryotic initiation factors (eIF) 4E in many crops. However, the sources of such variability for breeding can be limited for certain crop species, while new virus strains continue to emerge. Different methods of mutagenesis have been applied to inactivate the eIF4E genes to generate virus resistance, but with limited success due to the physiological importance of translation factors and their redundancy. Here, we employed genome editing approaches at the base level to induce non-synonymous mutations in the eIF4E1 gene and create genetic diversity in cherry tomato (Solanum lycopersicum var. cerasiforme). We sequentially edited the genomic sequences coding for two regions of eIF4E1 protein, located around the cap-binding pocket and known to be important for susceptibility to potyviruses. We show that the editing of only one of the two regions, by gene knock-in and base-editing, respectively, is not sufficient to provide resistance. However, combining amino acid mutations in both regions resulted in resistance to multiple potyviruses without affecting its functionality in translation initiation. Meanwhile, we report that extensive base editing in exonic region can alter RNA splicing pattern, resulting in gene knockout. Altogether our work demonstrates that precision editing allows to design plant factors based on the knowledge on evolutionarily selected alleles and enlarge the gene pool to potentially provide advantageous phenotypes such as pathogen resistance.

Cet article est un compte-rendu du livre : Kevin Saliou, Le Réseau de Lautréamont. Itinéraire et stratégies d’Isidore Ducasse, Paris : Classiques Garnier, coll. « Études romantiques et dix-neuviémistes », 2021, 318 pages, EAN 9782406115120.

ObjectiveTo assess left atrial appendage (LAA) thrombus detection using a novel cardiac computed tomography (CT) protocol specifically prior to direct current cardioversion (DCCV).BackgroundTransesophageal echocardiography (TEE) is the gold standard in evaluating the LAA prior to DCCV for atrial fibrillation (AF) or flutter (AFL). The COVID-19 pandemic has restricted availability of TEE and anesthesia support.MethodsProspective cohort of consecutive patients with uncontrolled AF/AFL referred for DCCV from March 2020 to March 2021 were enrolled. CT evaluation of LAA was performed with an initial arterial and subsequent 30-second delayed acquisition to exclude thrombus prior to DCCV. Primary end points were to assess safety and outcomes.ResultsA total of 161 patients were included; mean age 69.8 ± 11.1 years; mean CHA2DS2-VASc 3.4 ± 1.7; and HAS-BLED 1.8 ± 0.9. Median follow-up 175 (105-267) days with zero cardiac-related deaths, and no episodes of TIA or embolic stroke. There was no statistically significant change in mean glomerular filtration rate (GFR) in the study population between the pre- and post-GFR measurements (73.9 ± 21.0 vs 72.7 ± 20.3; p=0.104). Overall mean total dose length product (DLP) was 1042.8 ± 447.5 mGy*cm. Modifying the CT protocol to a narrower 8-cm axial coverage had a statistically significant decrease in total DLP (from 1130.6 ± 464.1 mGy*cm to 802.1 ± 286.4 mGy*cm; PConclusionCardiac CT is both a safe and feasible alternative imaging to TEE for patients prior to DCCV.PerspectivesCompetency in Medical KnowledgeCardiac CT is a powerful tool for the evaluation of left atrial appendage and detection of thrombus prior to direct current cardioversion.Translational OutlookOur protocol was implemented with the restrictions during COVID-19 in mind, yet CT can be a viable tool beyond the pandemic; future randomized clinical trials can bridge the gap between CT and TEE in the setting of cardioversion and help elucidate its safety profile further.

Recent observations have shown that the atmospheres of ultra hot Jupiters (UHJs) commonly possess temperature inversions, where the temperature increases with increasing altitude. Nonetheless, which opacity sources are responsible for the presence of these inversions remains largely observationally unconstrained. We used LBT/PEPSI to observe the atmosphere of the UHJ KELT-20 b in both transmission and emission in order to search for molecular agents which could be responsible for the temperature inversion. We validate our methodology by confirming previous detections of Fe I in emission at $16.9\sigma$. Our search for the inversion agents TiO, VO, FeH, and CaH results in non-detections. Using injection-recovery testing we set $4\sigma$ upper limits upon the volume mixing ratios for these constituents as low as $\sim1\times10^{-9}$ for TiO. For TiO, VO, and CaH, our limits are much lower than expectations from an equilibrium chemical model, while we cannot set constraining limits on FeH with our data. We thus rule out TiO and CaH as the source of the temperature inversion in KELT-20 b, and VO only if the line lists are sufficiently accurate., Comment: 18 pages, 11 figures. Accepted for publication in AJ

Decline and recovery timescales surrounding eclipse are indicative of the controlling physical processes in Io’s atmosphere. Recent studies have established that the majority of Io’s molecular atmosphere, SO2 and SO, condenses during its passage through Jupiter’s shadow. The eclipse response of Io’s atomic atmosphere is less certain, having been characterized solely by ultraviolet aurorae. Here we explore the response of optical aurorae for the first time. We find oxygen to be indifferent to the changing illumination, with [O i] brightness merely tracking the plasma density at Io’s position in the torus. In shadow, line ratios confirm sparse SO2 coverage relative to O, since their collisions would otherwise quench the emission. Io’s sodium aurora mostly disappears in eclipse and e-folding timescales, for decline and recovery differ sharply: ∼10 minutes at ingress and nearly 2 hr at egress. Only ion chemistry can produce such a disparity; Io’s molecular ionosphere is weaker at egress due to rapid recombination. Interruption of a NaCl+ photochemical pathway best explains Na behavior surrounding eclipse, implying that the role of electron impact ionization is minor relative to photons. Auroral emission is also evident from potassium, confirming K as the major source of far red emissions seen with spacecraft imaging at Jupiter. In all cases, direct electron impact on atomic gas is sufficient to explain the brightness without invoking significant dissociative excitation of molecules. Surprisingly, the nonresponse of O and rapid depletion of Na is opposite the temporal behavior of their SO2 and NaCl parent molecules during Io’s eclipse phase.

Sarcopenia is a progressive muscle disorder increasing with age that may lead to mobility disability. SARA program strives to develop a viable option to treat community dwelling older adults suffering from sarcopenia. SARA-INT is a randomized three-arm interventional study (BIO101 175 mg bid / BIO101 350 mg bid / placebo) with treatment duration of 6 months. Eligibility criteria for sarcopenia were meeting FNIH criteria and Short Physical Performance Battery (SPPB) score ≤ 8/12 in men and women aged ≥ 65 years; primary endpoint was the 400-meter walking test (400MWT). 233 participants aged 65 years and older were randomized, 232 and 156 participants were included in the Full Analysis Set (FAS) and Per-Protocol (PP) populations, respectively. Due to COVID-19 pandemic, most end-of-treatment efficacy assessments are missing for 55% of the participants, reducing the studies’ power. BIO101 350 mg bid treatment led to an improvement in the primary endpoint, the gait speed from the 400MWT of 0.07 m/s in the FAS population (not statistically significant) and of 0.09 m/s in the PP population (nominally statistically significant, p=0.008) after 6 months; this is close to MCID in sarcopenia (0.1 m/s). BIO101 350mg bid treatment effect on the 400MWT is confirmed in PP sub-populations at high risk of mobility disability. Trends were observed with other endpoints. BIO101 showed a very good safety profile at both doses. Biophytis will initiate the phase 3 program by end 2022, targeting a severe sarcopenic population. Outcomes of the interactions with regulatory agencies on study design will be presented.

Genome editing in the cultivated potato (Solanum tuberosum), a vegetatively propagated and highly heterozygous species, constitutes a promising trail to directly improve traits into elite cultivars. With the recent and successful development of the clustered regularly interspaced short palindromic repeat (CRISPR)-Cas9 system in eukaryotic cells, the plant science community has gained access to a powerful, inexpensive, and easy-to-use toolbox to target and inactivate/modify specific genes. The specificity and versatility of the CRISPR-Cas9 system rely on a variable 20 bp spacer sequence at the 5' end of a single-guide RNA (sgRNA), which directs the SpCas9 (Streptococcus pyogenes) nuclease to cut the target DNA at a precise locus with no or low off-target events. Using this system, we and other teams were able to knock out specific genes in potato through the error-prone non-homologous end-joining (NHEJ) DNA repair mechanism. In this chapter, we describe strategies to design and clone spacer sequences into CRISPR-SpCas9 plasmids. We show how these constructs can be used for Agrobacterium-mediated stable transformation or transient transfection of protoplasts, and we describe the optimization of these two delivery methods, as well as of the plant regeneration processes. Finally, the molecular screening and characterization of edited potato plants are also described, mainly relying on PCR-based methods such as high-resolution melt (HRM) analysis.

We evaluated the performance of the QIAprepamp Viral RNA UM Kit (Qiagen) for SARS-CoV-2 detection. It displayed specificity and sensitivity required for SARS-CoV-2 RNA detection from swab transport media without RNA extraction. This method identifies accurately patients at risk of transmission while saving time and cost of extraction.

Percutaneous left atrial appendage (LAA) closure has become an attractive alternative to long-term anticoagulation for prevention of stroke in patients with atrial fibrillation ([1][1]). However, there is great variability in LAA anatomy among patients ([2][2]). Therefore, advanced cardiac imaging

With the global rise of human-mediated translocations and invasions, it is critical to understand the genomic consequences of hybridization and mechanisms of range expansion. Conventional wisdom is that high genetic drift and loss of genetic diversity due to repeated founder effects will constrain introduced species. However, reduced genetic variation can be countered by behavioral aspects and admixture with other distinct populations. As planned invasions, classical biological control (biocontrol) agents present important opportunities to understand the mechanisms of establishment and spread in a novel environment. The ability of biocontrol agents to spread and adapt, and their effects on local ecosystems, depends on genomic variation and the consequences of admixture in novel environments. Here we use a biocontrol system to examine the genome-wide outcomes of introduction, spread, and hybridization in four cryptic species of a biocontrol agent, the tamarisk beetle (Diorhabda carinata, D. carinulata, D. elongata, and D. sublineata), introduced from six localities across Eurasia to control the invasive shrub tamarisk (Tamarix spp.) in western North America. We assembled a de novo draft reference genome and applied RADseq to over 500 individuals from laboratory cultures, the native ranges, and across the introduced range. Despite evidence of a substantial genetic bottleneck among D. carinulata in N. America, populations continue to establish and spread, possibly due to aggregation behavior. We found that D. carinata, D. elongata, and D. sublineata hybridize in the field to varying extents, with D. carinata x D. sublineata hybrids being the most abundant. Genetic diversity was greater at sites with hybrids, highlighting potential for increased ability to adapt and expand. Our results demonstrate the complex patterns of genomic variation that can result from introduction of multiple ecotypes or species for biocontrol, and the importance of understanding them to predict and manage the effects of biocontrol agents in novel ecosystems.

Genomes comprise a large fraction of repetitive sequences folded into constitutive heterochromatin to protect genome integrity and cell identity.De novoformation of heterochromatin during preimplantation development is an essential step for preserving the ground-state of pluripotency and the self-renewal capacity of embryonic stem cells (ESCs). Yet, the molecular mechanisms responsible for the remodeling of constitutive heterochromatin are largely unknown. Here, we find that DAXX, an H3.3 chaperone, is essential for ESCs maintenance in the ground-state of pluripotency. DAXX accumulates at pericentromeric regions, and recruits PML and SETDB1, thereby promoting heterochromatin formation. In absence of DAXX or PML, the 3D-architecture and physical properties of pericentric and peripheral heterochromatin are disrupted, resulting in derepression of major satellite DNA, transposable elements and genes associated with the nuclear lamina. Using epigenome editing tools, we observe that H3.3, and specifically H3.3K9 modification, directly contribute to maintaining pericentromeric chromatin conformation. Altogether, our data reveal that DAXX is crucial for the maintenance and 3D-organization of the heterochromatin compartment and protects ESCs viability.

Radiofrequency ablation is commonly performed in the management of incessant ventricular tachycardias. Pre-procedural planning using different imaging modalities including cardiac computed tomography and cardiac magnetic resonance plays an integral role in understanding the anatomy and potential origin of the arrhythmias to guide successful targeted ablation.

Genome editing in the cultivated potato (Solanum tuberosum), a vegetatively propagated and highly heterozygous species, constitutes a promising trail to directly improve traits into elite cultivars. With the recent and successful development of the clustered regularly interspaced short palindromic repeat (CRISPR)-Cas9 system in eukaryotic cells, the plant science community has gained access to a powerful, inexpensive, and easy-to-use toolbox to target and inactivate/modify specific genes. The specificity and versatility of the CRISPR-Cas9 system rely on a variable 20 bp spacer sequence at the 5' end of a single-guide RNA (sgRNA), which directs the SpCas9 (Streptococcus pyogenes) nuclease to cut the target DNA at a precise locus with no or low off-target events. Using this system, we and other teams were able to knock out specific genes in potato through the error-prone non-homologous end-joining (NHEJ) DNA repair mechanism. In this chapter, we describe strategies to design and clone spacer sequences into CRISPR-SpCas9 plasmids. We show how these constructs can be used for Agrobacterium-mediated stable transformation or transient transfection of protoplasts, and we describe the optimization of these two delivery methods, as well as of the plant regeneration processes. Finally, the molecular screening and characterization of edited potato plants are also described, mainly relying on PCR-based methods such as high-resolution melt (HRM) analysis.

Little is known about Earth quasi-satellites, a class of near-Earth small solar system bodies that orbit the sun but remain close to the Earth, because they are faint and difficult to observe. Here we use the Large Binocular Telescope (LBT) and the Lowell Discovery Telescope (LDT) to conduct a comprehensive physical characterization of quasi-satellite (469219) Kamo`oalewa and assess its affinity with other groups of near-Earth objects. We find that (469219) Kamo`oalewa rotates with a period of 28.3 (+1.8/-1.3) minutes and displays a reddened reflectance spectrum from 0.4-2.2 microns. This spectrum is indicative of a silicate-based composition, but with reddening beyond what is typically seen amongst asteroids in the inner solar system. We compare the spectrum to those of several material analogs and conclude that the best match is with lunar-like silicates. This interpretation implies extensive space weathering and raises the prospect that Kamo`oalewa could comprise lunar material., Comment: Published in Nature Communications Earth and Environment

This is an Open Access article distributed under the terms of the Creative Commons Attribution License (http://creativecommons.org/licenses/by/4.0/), which permits unrestricted reuse, distribution, and reproduction in any medium, provided the original work is properly cited., Gamma-ray bursts (GRBs) are classified into long and short events. Long GRBs (LGRBs) are associated with the end states of very massive stars, while short GRBs (SGRBs) are linked to the merger of compact objects. GRB 200826A was a peculiar event, because by definition it was an SGRB, with a rest-frame duration of ∼0.5 s. However, this event was energetic and soft, which is consistent with LGRBs. The relatively low redshift (z = 0.7486) motivated a comprehensive, multiwavelength follow-up campaign to characterize its host, search for a possible associated supernova (SN), and thus understand the origin of this burst. To this aim we obtained a combination of deep near-infrared (NIR) and optical imaging together with spectroscopy. Our analysis reveals an optical and NIR bump in the light curve whose luminosity and evolution are in agreement with several SNe associated to LGRBs. Analysis of the prompt GRB shows that this event follows the Ep,i–Eiso relation found for LGRBs. The host galaxy is a low-mass star-forming galaxy, typical of LGRBs, but with one of the highest star formation rates, especially with respect to its mass ($\mathrm{log}{M}_{* }/{M}_{\odot }=8.6$, SFR ∼ 4.0 M⊙ yr−1). We conclude that GRB 200826A is a typical collapsar event in the low tail of the duration distribution of LGRBs. These findings support theoretical predictions that events produced by collapsars can be as short as 0.5 s in the host frame and further confirm that duration alone is not an efficient discriminator for the progenitor class of a GRB. © 2022. The Author(s). Published by the American Astronomical Society., A.R. acknowledges support from the INAF project Premiale Supporto Arizona & Italia. B.R. would like to acknowledge the assistance and support of R. T. Gatto. D.A.K. acknowledges support from Spanish National Research Project RTI2018-098104-J-I00 (GRBPhot). P.D'A. acknowledges funding from the Italian Space Agency, contract ASI/INAF No. I/004/11/4. L.I. was supported by two grants from VILLUM FONDEN (project No. 16599 and 25501). A.N.G. and S.K. acknowledge financial support from grants DFG Kl 766/16-3, DFG Kl 766/18-1, and DFG RA 2484/1-3. A.N.G. acknowledges support from Thüringer Landessternwarte Tautenburg. A.S.P., P.Y.M., and A.A.V. acknowledge support from RSF grant 18-12-00378. S.S. acknowledges support from the G.R.E.A.T. research environment, funded by Vetenskapsrådet, the Swedish Research Council, project No. 2016-06012. A.R., E.Pi., P.D'A., L.A., A.P., E.Pa., S.S., G.S., S.C., V.D'E., M.D.V., and A.M. acknowledge support from PRIN-MIUR 2017 (grant 20179ZF5KS). The LBT is an international collaboration among institutions in the United States, Italy, and Germany. The LBT Corporation partners are the University of Arizona on behalf of the Arizona Board of Regents; Istituto Nazionale di Astrofisica, Italy; LBT Beteiligungsgesellschaft, Germany, representing the Max-Planck Society, the Leibniz Institute for Astrophysics Potsdam, and Heidelberg University; and the Ohio State University, representing OSU, University of Notre Dame, University of Minnesota, and University of Virginia. This work made use of data supplied by the UK Swift Science Data Centre at the University of Leicester., With funding from the Spanish government through the Severo Ochoa Centre of Excellence accreditation SEV-2017-0709.

Detailed methods; figures displaying sequencing coverage, relationships among selection metrics, and gene set overlaps. Tables displaying sample sizes, ANGSD settings, effective population size estimates, candidate gene information, and PAML results.

The Facility AO systems at the LBT are based around the two Adaptive Secondary Mirrors (ASM) and the Pyramid Wavefront Sensors (PWFS), the latter being recently upgraded as part of the SOUL project in order to provide improved image quality performance and greater faint target sensitivity, at the LUCI and LBTI ports. These represent operational AO Systems with unique challenges for maintaining their optimal operational status. Based on our experience, especially over the last seven years, we present our approach to provide the readiness of the AO systems at all times including routine calibration, monitoring, and maintenance activities necessary to keep their performance at an optimal level. We also address intervention activities to improve the ASMs’ reliability and robustness.

Since 2017 LBTO, in partnership with GMTO, has been developing a laser-trussed based metrology system for the active alignment of telescope main optical components to each other and to instruments. The effort has addressed needs of both organizations; LBTO with the opportunity to assess the performance of a new technological approach to telescope alignment, and the GMTO with the opportunity to prototype and field-test a system that has been identified as a crucial "missing link" in the active-optics chain between open-loop modelling and wavefront-sensing for ELT-scale telescopes. Following two years of effort the positive results so far obtained have convinced LBTO, in 2019, to commence to develop an integrated operational active-optics system based on this technological approach. A team drawn from LBTO, Steward Observatory, GMTO, the Wyant College of Optical Sciences and Mersenne Optical Consulting are currently completing the first phase of this Telescope Metrology System (TMS). This paper shall describe the system in detail and report on progress, current status, and future goals.

The Adaptive Optics (AO) system at the Large Binocular Telescope (LBT) in conjunction with the f/30 camera on the LBT Utility Camera in the Infrared instruments (LUCI) can achieve diffraction limited image quality over a 30" × 30" field of view (FOV). The AO system also includes the ability to deliver only 11 modes of correction (including tip and tilt) to remove residual aberrations and jitter. When combined with the f/3.75 camera on either LUCI, this Enhanced Seeing Mode (ESM) can achieve an uniform angular resolution of 0".22 over a 4' × 4' FOV in the best natural seeing conditions. Further, unlike full AO, ESM can be used for binocular longslit and multi-object high-resolution spectroscopy (R~10,000). It has been further demonstrated that even in poor seeing conditions (θ << 1′′.5) the image quality delivered to the LUCI focal stations is improved by 2-3× from 1-2.5 microns. It is proposed that ESM should become a standard observational mode for near-Infrared LBT observations.

Presented here is a review of the status of facility instruments at the Large Binocular Telescope Observatory (LBTO). These include: the prime-focus optical Large Binocular Cameras (LBCs); optical Multi-Object Double Spectrograph (MODS) for imaging and spectroscopy; and the two LBT Utility Camera in the Infrared (LUCIs) for imaging and spectroscopy, which include the commissioning of the Single conjugated adaptive Optics Upgrade for LBT (SOUL). Recently, the Potsdam Echelle Polarietric and Spectroscopic Instrument (PEPSI), a fiber-fed high resollution optical echelle spectrograph with polarimetry capabilities, has transitioned from a Principal Investigator (PI) instrument to a facility instrument. We discuss the ”binocular lifestyle” including the unique challenges of using LBT in three ways: Duplex mode, with identical configurations on both sides (effectively an 11.8 meter mirror); Fraternal Twin (same instruments with different configurations) or Mixed mode, (different instruments on each side) which gives observers two 8.4 meter telescopes to use; or 22.65 meters in interferometry (LBTI) mode. We also review recent changes in nighttime operations at the observatory in response to the COVID-19 pandemic and plans for the implementation of the Health and Instrument Performance plan for the Observatory (HIPO), a program to proactively monitor the health and stability of the facility instruments.

N-retinylidene-N-retinylethanolamine (A2E) plays a central role in age-related macular degeneration (AMD) by inducing angiogenesis and inflammation. A2E effects are mediated at least partly via the retinoic acid receptor (RAR)-α. Here we show that A2E binds and transactivates also peroxisome proliferator-activated receptors (PPAR) and retinoid X receptors (RXR). 9’-cis-norbixin, a di-apocarotenoid is also a ligand of these nuclear receptors (NR). Norbixin inhibits PPAR and RXR transactivation induced by A2E. Moreover, norbixin reduces protein kinase B (AKT) phosphorylation, NF-κB and AP-1 transactivation and mRNA expression of the inflammatory interleukins (IL) -6 and -8 and of vascular endothelial growth factor (VEGF) enhanced by A2E. By contrast, norbixin increases matrix metalloproteinase 9 (MMP9) and C-C motif chemokine ligand 2 (CCL2) mRNA expression in response to A2E. Selective PPAR-α, -β/δ and –γ antagonists inhibit the expression of IL-6 and IL-8 while only the antagonist of PPAR-γ inhibits the transactivation of NF-κB following A2E exposure. In addition, a cocktail of all three PPARs antagonists and also HX531, an antagonist of RXR reproduce norbixin effects on inflammation. Altogether, A2E’s deleterious biological effects could be inhibited through PPAR and RXR regulation. Moreover, the modulation of these NR by norbixin may open new avenues for the treatment of AMD.

COVID-19, caused by severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2), has reached pandemic proportions with negative impacts on global health, the world economy and human society. The clinical picture of COVID-19, and the fact that Angiotensin converting enzyme 2 (ACE2) is a receptor of SARS-CoV-2, suggests that SARS-CoV-2 infection induces an imbalance in the renin–angiotensin system (RAS). We review clinical strategies that are attempting to rebalance the RAS in COVID-19 patients by using ACE inhibitors, angiotensin receptor blockers, or agonists of angiotensin-II receptor type 2 or Mas receptor (MasR). We also propose that the new MasR activator BIO101, a pharmaceutical grade formulation of 20-hydroxyecdysone that has anti-inflammatory, anti-fibrotic and cardioprotective properties, could restore RAS balance and improve the health of COVID-19 patients who have severe pneumonia., Teaser By rebalancing the renin–angiotensin system (RAS), BIO101 (20-hydroxyecdysone) could improve cardio-respiratory functions, limit the requirement for mechanical ventilation and reduce mortality in severely ill COVID-19 patients who are infected by SARS-CoV-2.

Large ground-based telescopes are prone to perturbations caused by environmental factors that affect the mechanical structure of the telescope that can cause collimation loss and image quality degradation. The Telescope Metrology System (TMS) is a metrology method under development at the Giant Magellan Telescope (GMT) and prototyped on the Large Binocular Telescope (LBT) to monitor and maintain collimation and pointing. TMS measures the precise position and orientation of a telescope’s primary mirror in relation to other telescope elements. Currently, prototyping has progressed to TMS operation at prime focus between LBT’s two 8.4m primary mirrors and the Large Binocular Camera (LBC), a pair of prime focus correctors and wide-field detectors. TMS utilizes a multi-channel absolute distance measuring (ADM) interferometer to create a laser truss by determining the distance between fixed points on the primary mirror and the LBC. By performing a kinematic analysis of the ADM data, the relative position and orientation of the primary mirror and LBC can be determined. With knowledge of the position of the telescope, an optical layout model can be created using TMS data as input. This allows for iterative simulation of field aberrations and loss in image quality due to misalignment of the telescope. This will allow for collimation and pointing to be actively monitored and maintained during an observation. This paper will discuss the process of implementing TMS on LBT and the challenges that arose.

Tasmanian devils (Sarcophilus harrisii) are evolving in response to a unique transmissible cancer, devil facial tumour disease (DFTD), first described in 1996. Persistence of wild populations and the recent emergence of a second independently evolved transmissible cancer suggest that transmissible cancers may be a recurrent feature in devils. Here we compared signatures of selection across temporal scales to determine whether genes or gene pathways under contemporary selection (6-8 generations) have also been subject to historical selection (65-85 million years), and test for recurrent selection in devils. First, we used a targeted sequencing approach, RAD-capture, to identify genomic regions subject to rapid evolution in approximately 2,500 devils in six populations as DFTD spread across the species range. We documented genome-wide contemporary evolution, including 186 candidate genes related to cell cycling and immune response. Then we used a molecular evolution approach to identify historical positive selection in devils compared to other marsupials and found evidence of selection in 1,773 genes. However, we found limited overlap across time scales, with historical selection detected in only 16 contemporary candidate genes, and no overlap in enriched functional gene sets. Our results are consistent with a novel, multi-locus evolutionary response of devils to DFTD. Our results can inform management actions to conserve adaptive potential of devils by identifying high priority targets for genetic monitoring and maintenance of functional diversity in managed populations.

With the conclusion of the third observing run for Advanced LIGO/Virgo (O3), we present a detailed analysis of both triggered and serendipitous observations of 17 gravitational wave (GW) events (7 triggered and 10 purely serendipitous) from the Searches After Gravitational-waves Using ARizona Observatories (SAGUARO) program. We searched a total of 4935 deg$^2$ down to a median 5$��$ transient detection depth of 21.1 AB mag using the Mt Lemmon 1.5 m telescope, the discovery engine for SAGUARO. In addition to triggered events within 24~hours, our transient search encompassed a time interval following GW events of $, 44 pages, 21 figures, 2 tables, submitted to ApJ

Genome editing has become a major tool for both functional studies and plant breeding in several species. Besides generating knockouts through the classical CRISPR-Cas9 system, recent development of CRISPR base editing holds great and exciting opportunities for the production of gain-of-function mutants. The PAM requirement is a strong limitation for CRISPR technologies such as base editing, because the base substitution mainly occurs in a small edition window. As precise single amino-acid substitution can be responsible for functions associated to some domains or agronomic traits, development of Cas9 variants with relaxed PAM recognition is of upmost importance for gene function analysis and plant breeding. Recently, the SpCas9-NG variant that recognizes the NGN PAM has been successfully tested in plants, mainly in monocotyledon species. In this work, we studied the efficiency of SpCas9-NG in the model moss Physcomitrella patens and two Solanaceae crops (Solanum lycopersicum and Solanum tuberosum) for both classical CRISPR-generated gene knock-out and cytosine base editing. We showed that the SpCas9-NG greatly expands the scope of genome editing by allowing the targeting of non-canonical NGT and NGA PAMs. The CRISPR toolbox developed in our study opens up new gene function analysis and plant breeding perspectives for model and crop plants.

Phytoecdysteroids are molecules derived from sterol metabolism and found in many plants. They display a wide array of pharmacological effects on mammals (e.g. anabolic, anti-diabetic). Although these effects have been long established, the molecular targets involved remain to be identified. Like endogenous steroid hormones and bile acids, which are biochemically related, ingested or injected phytoecdysteroids undergo a set of reactions in mammals leading to the formation of numerous metabolites, only some of which have been so far identified, and it is presently unknown whether they represent active metabolites or inactivation products. In the large intestine, ecdysteroids undergo efficient 14-dehydroxylation. Other changes (reductions, epimerization, side-chain cleavage) are also observed, but whether these occur in the liver and/or large intestine is not known. The purpose of this study was to investigate the pharmacokinetics of 20-hydroxyecdysone (20E), the most common phytoecdysteroid, when administered to mice and rats, using, when required, tritium-labelled molecules to permit metabolic tracking. Bioavailability, the distribution of radioactivity and the kinetics of formation of metabolites were followed for 24−48 hours after ingestion and qualitative and quantitative analyses of circulating and excreted compounds were performed. In mice, the digestive tract always contains the majority of the ingested 20E. Within 30 min after ingestion, 20E reaches the large intestine, where microorganisms firstly remove the 14-hydroxyl group and reduce the 6-one. Then a very complex set of metabolites (not all of which have yet been identified) appears, which correspond to poststerone derivatives formed in the liver. We have observed that these compounds (like bile acids) undergo an entero-hepatic cycle, involving glucuronide conjugation in the liver and subsequent deconjugation in the intestine. Despite the very short half-life of ecdysteroids in mammals, this entero-hepatic cycle helps to maintain their plasma levels at values which, albeit low (≤0.2 μM), would be sufficient to evoke several pharmacological effects. Similar 20E metabolites were observed in mice and rats; they include in particular 14-deoxy-20E, poststerone and 14-deoxypoststerone and their diverse reduction products; the major products of this metabolism have been unambiguously identified. The major sites of metabolism of exogenous ecdysteroids in mammals are the large intestine and the liver. The entero-hepatic cycle contributes to the metabolism and to maintaining a low, but pharmacologically significant, concentration of ecdysteroids in the blood for ca. 24 h after ingestion. These data, together with parallel in vitro experiments provide a basis for the identification of 20E metabolite(s) possibly involved in the physiological effects associated with ecdysteroids in mammals.

This paper revisits the debate about cognitive phenomenology. It elaborates, defends, and improves on our earlier proposal for resolving that debate, according to which the test for irreducible phenomenology is the presence of explanatory gaps. After showing how proposals like ours have been misunderstood or misused by others, we deploy our operationalization to argue that the correct way to align the debate over cognitive phenomenology is not between sensory and (alleged) cognitive phenomenology, but rather between non-conceptual and (alleged) conceptual or propositional phenomenology. In doing so we defend three varieties of non-sensory (amodal)1 non-conceptual phenomenology: valence, a sense of approximate number, and a sense of elapsed time.

Plumage coloration in birds can be of major importance to mate selection, social signaling, or predator avoidance. Variations in plumage coloration related to sex, age class, or seasons have been widely studied, but the effect of other factors such as climate is less known. In this study, we examine how carotenoid-based plumage coloration and sexual dichromatism of the Hawai‘i ‘Amakihi (Chlorodrepanis virens) varies with rainfall and temperature on Hawai‘i Island. We also examined whether Hawai‘i ‘Amakihi plumage coloration patterns follow Gloger’s rule, which states that animals in wetter climates have darker coloration. Hawai‘i ‘Amakihi were mist-netted and banded at 12 sites representing six major climatic zones on Hawai‘i Island. Feather samples were collected from two body regions: the breast and rump. Using spectrophotometry, we recorded coloration using measures of hue, saturation, and brightness. We conducted sex determination by polymerase chain reaction to confirm the sex of birds sampled. We found that the plumage coloration of Hawai‘i ‘Amakihi varied with both temperature and rainfall. ‘Amakihi plumage’s brightness showed a quadratic relationship with rainfall, contrary to Gloger’s rule, and decreased with temperature. Saturation depended on the interaction between temperature and rainfall. Increases in rainfall also increased saturation in warm areas, while they reduced saturation when the temperature was low. Finally, we found chromatic differences among sexes, but sexual dichromatism was not affected by the climatic conditions. This study provides evidence that rainfall and temperature play an important role in determining the plumage traits of Hawai‘i ‘Amakihi.