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ABSTRACT This study investigates a previously unreported stress signal transduced as crosstalk between the cell wall integrity (CWI) pathway and the septation initiation network (SIN). Echinocandins, which target cell wall synthesis, are widely used to treat mycoses. Their efficacy, however, is species specific. Our findings suggest that this is due largely to CWI–SIN crosstalk and the ability of filamentous species to fortify with septa in response to echinocandin stress. To better understand this crosstalk, we used a microscopy-based assay to measure septum density, aiming to understand the septation response to cell wall stress. The echinocandin micafungin, an inhibitor of β-(1,3)-glucan synthase, was employed to induce this stress. We observed a strong positive correlation between micafungin treatment and septum density in wild-type strains. This finding suggests that CWI activates SIN under cell wall stress, increasing septum density to protect against cell wall failure. More detailed investigations, with targeted knockouts of CWI and SIN signaling proteins, enabled us to identify crosstalk occurring between the CWI kinase, MpkA, and the SIN kinase, SepH. This discovery of the previously unknown crosstalk between the CWI and SIN pathways not only reshapes our understanding of fungal stress responses, but also unveils a promising new target pathway for the development of novel antifungal strategies. IMPORTANCEEchinocandin-resistant species pose a major challenge in clinical mycology by rendering one of only four lines of treatment, notably one of the two that are well-tolerated, ineffective in treating systemic mycoses of these species. Previous studies have demonstrated that echinocandins fail against highly polarized fungi because they target only apical septal compartments. It is known that many filamentous species respond to cell wall stress with hyperseptation. In this work, we show that echinocandin resistance hinges on this dynamic response, rather than on innate septation alone. We also describe, for the first time, the signaling pathway used to deploy the hyperseptation response. By disabling this pathway, we were able to render mycelia susceptible to echinocandin stress. This work enhances our microbiological understanding of filamentous fungi and introduces a potential target to overcome echinocandin-resistant species. 

Context.Stars form preferentially in clusters embedded inside massive molecular clouds, many of which contain high-mass stars. Thus, a comprehensive understanding of star formation requires a robust and statistically well-constrained characterization of the formation and early evolution of these high-mass star clusters. To achieve this, we designed the ALMAGAL Large Program that observed 1017 high-mass star-forming regions distributed throughout the Galaxy, sampling different evolutionary stages and environmental conditions. Aims.In this work, we present the acquisition and processing of the ALMAGAL data. The main goal is to set up a robust pipeline that generates science-ready products, that is, continuum and spectral cubes for each ALMAGAL field, with a good and uniform quality across the whole sample. Methods.ALMAGAL observations were performed with the Atacama Large Millimeter/submillimeter Array (ALMA). Each field was observed in three different telescope arrays, being sensitive to spatial scales ranging from ≈1000 au up to ≈0.1 pc. The spectral setup allows sensitive (≈0.1 mJy beam⁻¹) imaging of the continuum emission at 219 GHz (or 1.38 mm), and it covers multiple molecular spectral lines observed in four different spectral windows that span about ≈4 GHz in frequency coverage. We have designed a Python-based processing workflow to calibrate and image these observational data. This ALMAGAL pipeline includes an improved continuum determination, suited for line-rich sources; an automatic self-calibration process that reduces phase-noise fluctuations and improves the dynamical range by up to a factor ≈5 in about 15% of the fields; and the combination of data from different telescope arrays to produce science-ready, fully combined images. Results.The final products are a set of uniformly generated continuum images and spectral cubes for each ALMAGAL field, including individual-array and combined-array products. The fully combined products have spatial resolutions in the range 800–2000 au, and mass sensitivities in the range 0.02–0.07M_⊙. We also present a first analysis of the spectral line information included in the ALMAGAL setup, and its potential for future scientific studies. As an example, specific spectral lines (e.g., SiO and CH₃CN) at ≈1000 au scales resolve the presence of multiple outflows in clusters and will help us to search for disk candidates around massive protostars. Moreover, the broad frequency bands provide information on the chemical richness of the different cluster members, which can be used to study the chemical evolution during the formation process of star clusters. 

The Milky Way’s Central Molecular Zone (CMZ) differs dramatically from our local solar neighbourhood, both in the extreme interstellar medium conditions it exhibits (e.g. high gas, stellar, and feedback density) and in the strong dynamics at play (e.g. due to shear and gas influx along the bar). Consequently, it is likely that there are large-scale physical structures within the CMZ that cannot form elsewhere in the Milky Way. In this paper, we present new results from the Atacama Large Millimeter/submillimeter Array (ALMA) large programme ACES (ALMA CMZ Exploration Survey) and conduct a multi-wavelength and kinematic analysis to determine the origin of the M0.8–0.2 ring, a molecular cloud with a distinct ring-like morphology. We estimate the projected inner and outer radii of the M0.8–0.2 ring to be 79″ and 154″, respectively (3.1 pc and 6.1 pc at an assumed Galactic Centre distance of 8.2 kpc) and calculate a mean gas density >10⁴cm⁻³, a mass of ~10⁶M_⊙, and an expansion speed of ~20 km s⁻¹, resulting in a high estimated kinetic energy (>10⁵¹erg) and momentum (>10⁷M_⊙km s⁻¹). We discuss several possible causes for the existence and expansion of the structure, including stellar feedback and large-scale dynamics. We propose that the most likely cause of the M0.8–0.2 ring is a single high-energy hypernova explosion. To viably explain the observed morphology and kinematics, such an explosion would need to have taken place inside a dense, very massive molecular cloud, the remnants of which we now see as the M0.8–0.2 ring. In this case, the structure provides an extreme example of how supernovae can affect molecular clouds. 

Abstract Terrestrial Gamma‐ray Flashes (TGFs) are ten‐to‐hundreds of microsecond bursts of gamma‐rays produced when electrons in strong electric fields in thunderclouds are accelerated to relativistic energies. Space instruments have observed TGFs with source photon brightness down to ∼10¹⁷–10¹⁶. Based on space and aircraft observations, TGFs have been considered rare phenomena produced in association with very few lightning discharges. Space observations associated with lightning ground observations in the radio band have indicated that there exists a population of dimmer TGFs. Here we show observations of TGFs from aircraft altitude that were not detected by a space instrument viewing the same area. The TGFs were found through Monte Carlo modeling to be associated with 10¹⁵–10¹²photons at source, which is several orders of magnitude below what can be seen from space. Our results suggest that there exists a significant population of TGFs that are too weak to be observed from space. 

Context. A large fraction of stars form in clusters containing high-mass stars, which subsequently influences the local and galaxy-wide environment. Aims. Fundamental questions about the physics responsible for fragmenting molecular parsec-scale clumps into cores of a few thousand astronomical units (au) are still open, that only a statistically significant investigation with ALMA is able to address; for instance: the identification of the dominant agents that determine the core demographics, mass, and spatial distribution as a function of the physical properties of the hosting clumps, their evolutionary stage and the different Galactic environments in which they reside. The extent to which fragmentation is driven by clumps dynamics or mass transport in filaments also remains elusive. Methods. With the ALMAGAL project, we observed the 1.38 mm continuum and lines toward more than 1000 dense clumps in our Galaxy, withM≥ 500 M_⊙, Σ ≥ 0.1 g cm⁻²andd≤ 7.5 kiloparsec (kpc). Two different combinations of ALMA Compact Array (ACA) and 12-m array setups were used to deliver a minimum resolution of ∼1000 au over the entire sample distance range. The sample covers all evolutionary stages from infrared dark clouds (IRDCs) to H IIregions from the tip of the Galactic bar to the outskirts of the Galaxy. With a continuum sensitivity of 0.1 mJy, ALMAGAL enables a complete study of the clump-to-core fragmentation process down toM∼ 0.3 M_⊙across the Galaxy. The spectral setup includes several molecular lines to trace the multiscale physics and dynamics of gas, notably CH₃CN, H₂CO, SiO, CH₃OH, DCN, HC₃N, and SO, among others. Results. We present an initial overview of the observations and the early science product and results produced in the ALMAGAL Consortium, with a first characterization of the morphological properties of the continuum emission detected above 5σin our fields. We used “perimeter-versus-area” and convex hull-versus-area metrics to classify the different morphologies. We find that more extended and morphologically complex (significantly departing from circular or generally convex) shapes are found toward clumps that are relatively more evolved and have higher surface densities. Conclusions. ALMAGAL is poised to serve as a game-changer for a number of specific issues in star formation: clump-to-core fragmentation processes, demographics of cores, core and clump gas chemistry and dynamics, infall and outflow dynamics, and disk detections. Many of these issues will be covered in the first generation of papers that closely follow on the present publication. 

Impaired wound healing is a significant financial and medical burden. The synthesis and deposition of extracellular matrix (ECM) in a new wound is a dynamic process that is constantly changing and adapting to the biochemical and biomechanical signaling from the extracellular microenvironments of the wound. This drives either a regenerative or fibrotic and scar-forming healing outcome. Disruptions in ECM deposition, structure, and composition lead to impaired healing in diseased states, such as in diabetes. Valid measures of the principal determinants of successful ECM deposition and wound healing include lack of bacterial contamination, good tissue perfusion, and reduced mechanical injury and strain. These measures are used by wound-care providers to intervene upon the healing wound to steer healing toward a more functional phenotype with improved structural integrity and healing outcomes and to prevent adverse wound developments. In this review, we discuss bioengineering advances in 1) non-invasive detection of biologic and physiologic factors of the healing wound, 2) visualizing and modeling the ECM, and 3) computational tools that efficiently evaluate the complex data acquired from the wounds based on basic science, preclinical, translational and clinical studies, that would allow us to prognosticate healing outcomes and intervene effectively. We focus on bioelectronics and biologic interfaces of the sensors and actuators for real time biosensing and actuation of the tissues. We also discuss high-resolution, advanced imaging techniques, which go beyond traditional confocal and fluorescence microscopy to visualize microscopic details of the composition of the wound matrix, linearity of collagen, and live tracking of components within the wound microenvironment. Computational modeling of the wound matrix, including partial differential equation datasets as well as machine learning models that can serve as powerful tools for physicians to guide their decision-making process are discussed. 

Aims.The processes that determine the stellar initial mass function (IMF) and its origin are critical unsolved problems, with profound implications for many areas of astrophysics. The W43-MM2&MM3 mini-starburst ridge hosts a rich young protocluster, from which it is possible to test the current paradigm on the IMF origin. Methods.The ALMA-IMF Large Program observed the W43-MM2&MM3 ridge, whose 1.3 mm and 3 mm ALMA 12 m array continuum images reach a ~2500 au spatial resolution. We used both the best-sensitivity and the line-free ALMA-IMF images, reduced the noise with the multi-resolution segmentation techniqueMnGSeg, and derived the most complete and most robust core catalog possible. Using two different extraction software packages,getsfandGExt2D, we identified ~200 compact sources, whose ~100 common sources have, on average, fluxes consistent to within 30%. We filtered sources with non-negligible free-free contamination and corrected fluxes from line contamination, resulting in a W43-MM2&MM3 catalog of 205getsfcores. With a median deconvolved FWHM size of 3400 au, core masses range from ~0.1M_⊙to ~70M_⊙and thegetsfcatalog is 90% complete down to 0.8M_⊙.Results.The high-mass end of the core mass function (CMF) of W43-MM2&MM3 is top-heavy compared to the canonical IMF. Fitting the cumulative CMF with a single power-law of the formN(> logM) ∝M^α, we measuredα= −0.95 ± 0.04, compared to the canonicalα= −1.35 Salpeter IMF slope. The slope of the CMF is robust with respect to map processing, extraction software packages, and reasonable variations in the assumptions taken to estimate core masses. We explore several assumptions on how cores transfer their mass to stars (assuming a mass conversion efficiency) and subfragment (defining a core fragment mass function) to predict the IMF resulting from the W43-MM2&MM3 CMF. While core mass growth should flatten the high-mass end of the resulting IMF, core fragmentation could steepen it. Conclusions.In stark contrast to the commonly accepted paradigm, our result argues against the universality of the CMF shape. More robust functions of the star formation efficiency and core subfragmentation are required to better predict the resulting IMF, here suggested to remain top-heavy at the end of the star formation phase. If confirmed, the IMFs emerging from starburst events could inherit their top-heavy shape from their parental CMFs, challenging the IMF universality.