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Histones organize DNA within cellular nuclei, but they can be released from damaged cells. In peripheral tissues extracellular histones act as damage-associated molecular patterns (DAMPs) inducing pro-inflammatory activation of immune cells. Limited studies have considered DAMP-like activity of histones in the central nervous system (CNS); therefore, we studied the effects of extracellular histones on microglia, the CNS immunocytes, and on neuronal cells. Both the linker histone H1 and the core histone H3 induced pro-inflammatory activation of microglia-like cells by upregulating their secretion of NO and cytokines, including interferon-γ-inducible protein 10 (IP-10) and tumor necrosis factor-α (TNF). The selective inhibitors MMG-11 and TAK-242 were used to demonstrate involvement of toll-like receptors (TLR) 2 and 4, respectively, in H1-induced NO secretion by BV-2 microglia. H1, but not H3, downregulated the phagocytic activity of BV-2 microglia. H1 was also directly toxic to all neuronal cell types studied. We conclude that H1, and to a lesser extent H3, when released extracellularly, have the potential to act as a CNS DAMPs. Inhibition of the DAMP-like effects of extracellular histones on microglia and their neurotoxic activity represents a potential strategy for combating neurodegenerative diseases that are characterized by the adverse activation of microglia and neuronal death. • Extracellular histones were hypothesized to be DAMPs of the central nervous system. • H1 or H3 histones were applied directly to cultured microglial and neuronal cells. • Pro-inflammatory activation of murine and human microglia-like cells was observed. • H1-induced NO secretion by BV-2 microglia was reduced by TLR4 and TLR2 inhibitors. • H1, but not H3, was directly toxic to murine primary neurons and neuronal cell lines. [ABSTRACT FROM AUTHOR]

Objective Data Sources Study Design Data Extraction Principal Findings Conclusions This study aims to examine how variation in physicians' treatment decisions for newborn deliveries responds to changes in the hospital‐level norms for obstetric clinical decision‐making.All hospital‐based births in Florida from 2003 through 2017.Difference‐in‐differences approach is adopted that leverages obstetric unit closures as the source of identifying variation to exogenously shift obstetricians to a new, nearby hospital with different propensities to approach newborn deliveries less intensively.Births attributed to physicians continuously observed 2 years before the closure event and 2 years after the closure event (treatment group physicians) or for identical time periods around a randomly assigned placebo closure date (control group physicians).All of the physicians meeting our inclusion criteria shifted their births to a new hospital less than 20 miles from the hospital shuttering its obstetric unit. The new hospitals approached newborn births more conservatively, and treatment group physicians sharply became less aggressive in their newborn birth clinical management (e.g., use of C‐section). The immediate 11‐percentage point (33%) increase in delivering newborns without any procedure behavior change is statistically significant (p value <0.01) and persistent after the closure event; however, the physicians' payer and patient mix are unchanged.Obstetric physician behavior change appears highly malleable and sensitive to the practice patterns of other physicians delivering newborns at the same hospital. Incentives and policies that encourage more appropriate clinical care norms hospital‐wide could sharply improve physician treatment decisions, with benefits for maternal and infant outcomes. [ABSTRACT FROM AUTHOR]

In internal fertilisers, the precise timing of ovulation with the arrival of sperm at the site of fertilisation is essential for fertilisation success. In birds, mating is often not synchronised with ovulation, but instead females utilise specialised sperm storage tubules (SSTs) in the reproductive tract, which can ensure sperm are always available for fertilisation at the time of ovulation, whilst simultaneously providing a mechanism of post‐copulatory sexual selection. Despite the clear importance of SSTs for fertilisation success, we know little about the mechanisms involved in sperm acceptance, storage, and release. Furthermore, most research has been conducted on only a small number of species, based on which SSTs are usually assumed to look and function in the same way across all species. Here, we conduct a comparative exploration of SST morphology across 26 species of Galliformes. We show that SSTs, and the surrounding tissue, can vary significantly in morphology across species. We provide observational evidence that Galliformes exhibit at least 5 distinct categories of tubule types, including distinctive coiled and multi‐branched tubules, and describe 2 additional features of the surrounding tissue. We suggest functional explanations for variation in tubule morphology and propose next steps for future research. Our findings indicate that SSTs are likely to be far more variable than has previously been assumed, with potentially important consequences for our understanding of sperm storage in birds and post‐copulatory sexual selection in general. [ABSTRACT FROM AUTHOR]

Parkinson's disease is a progressive neurodegenerative disorder, predominantly of the motor system. Although some genetic components and cellular mechanisms of Parkinson's have been identified, much is still unknown. In recent years, emerging evidence has indicated that non-DNA-sequence variation (in particular epigenetic mechanisms) is likely to play a crucial role in the development and progression of the disease. Here, we present an up-to-date overview of epigenetic processes including DNA methylation, DNA hydroxymethylation, histone modifications and non-coding RNAs implicated in the brain of those with Parkinson's disease. We will also discuss the limitations of current epigenetic research in Parkinson's disease, the advantages of simultaneously studying genetics and epigenetics, and putative novel epigenetic therapies. [ABSTRACT FROM AUTHOR]

Aim: Species responses to global warming will depend on intraspecific diversity, yet studies of factors governing biogeographic patterns of variability are scarce. Here, we investigate the evolutionary processes underlying genetic and phenotypic diversity in the flightless and cold‐adapted grasshopper Sigaus piliferus, and project its suitable space in time. Location: Te Ika‐a‐Māui Aotearoa—North Island of New Zealand. Methods: We used mitochondrial sequences to investigate population connectivity and demographic trends using phylogeographic tools and neutrality statistics. Metric data were used to document phenotypic variation using naïve clustering. We used niche metrics to assess intraspecific niche variation, and niche modelling to investigate suitability under past and future scenarios. Multiple matrix regressions with randomization explored the processes contributing to phenotypic differentiation among grasshopper populations. Results: Niche models and demographic analyses suggest suitable space for this grasshopper was more restricted during glacial than interglacial stages. Genealogical relationships among ND2 haplotypes revealed a deep north–south split partly concordant with phenotypic and niche variation, suggesting two ecotypes that have mixed during recolonisation of the central volcanic region. Multiple matrix regressions with randomization indicate a link between climate and phenotypic differentiation inferred from leg and pronotum dimensions but not pronotum shape. Niche projections predict severe habitat reduction due to climate warming. Main conclusions: The current distribution and intraspecific diversity of S. piliferus reflect complex biogeographical scenarios consistent with Quaternary climates and volcanism. Phenotypic divergence appears adaptive. Current levels of genetic and phenotypic variation suggest adaptive potential, yet the pace of anthropogenic warming over the next 50 years could result in small populations that may collapse before adapting. Differences in niche features between diverging intraspecific lineages suggest distinct responses to climate change, and this has implications for prioritising conservation actions and management strategies. [ABSTRACT FROM AUTHOR]

In the face of rising population, erratic climate, resource depletion, and increased exposure to natural hazards, environmental monitoring is increasingly important. Satellite data form most of our observations of Earth. On-the-ground observations based on in situ sensor systems are crucial for these remote measurements to be dependable. Providing open-source options to rapidly prototype environmental datalogging systems allows quick advancement of research and monitoring programs. This paper introduces Loom, a development environment for low-power Arduino-programmable microcontrollers. Loom accommodates a range of integrated components including sensors, various datalogging formats, internet connectivity (including Wi-Fi and 4G Long Term Evolution (LTE)), radio telemetry, timing mechanisms, debugging information, and power conservation functions. Additionally, Loom includes unique applications for science, technology, engineering, and mathematics (STEM) education. By establishing modular, reconfigurable, and extensible functionality across components, Loom reduces development time for prototyping new systems. Bug fixes and optimizations achieved in one project benefit all projects that use Loom, enhancing efficiency. Although not a one-size-fits-all solution, this approach has empowered a small group of developers to support larger multidisciplinary teams designing diverse environmental sensing applications for water, soil, atmosphere, agriculture, environmental hazards, scientific monitoring, and education. This paper not only outlines the system design but also discusses alternative approaches explored and key decision points in Loom's development. [ABSTRACT FROM AUTHOR]

In galaxy cluster collisions, the gas can be separated from dark matter haloes. Abell 56 displays signatures of a dissociative bullet-like merger with a possible high-inclination angle between the plane of orbit and the sky. Our objective is to provide a comprehensive description of the features observed in the collision scenario of Abell 56. Additionally, we aim to apply a potential weak lensing mass bias correction attributed to the merger to evaluate its impact on our findings. To investigate this, we perform tailored hydrodynamical N -body simulations, varying the impact parameter. We initially identified an early scenario at 0.12 Gyr after the central passage that reproduces some observational features. However, the mean temperature of 9.7 keV exceeded the observed value. Our best model corresponds to the late scenario at 0.52 Gyr after the pericentre, reproducing observed features of Abell 56, with an inclination of 58°. These features include the offset of 103 kpc between the main gas density peak and the south dark matter density peak, gas morphology, a line-of-sight relative velocity of 184 km s−1, and a mean temperature of 6.7 keV. This late model provides a plausible scenario to describe the dynamics of Abell 56. The weak lensing mass bias did not significantly impact the overall dynamics of this cluster merger. [ABSTRACT FROM AUTHOR]

In this Article, we focus on a key dimension of commercial surveillance by data-intensive digital platforms that is too often treated as a supporting cast member instead of a star of the show: the concept of engagement. Engagement is, simply put, a measure of time, attention, and other interactions with a service. The economic logic of engagement is simple: more engagement equals more ads watched equals more revenue. Engagement is a lucrative digital business model, but it is problematic in several ways that lurk beneath the happy sloganeering of a "free" internet. Our goal in this Article is to isolate engagement as a distinct and dangerous concept that should be specifically regulated. There is a benefit to seeing past the glib justificatory rhetoric and taking a hard look at engagement-based, surveillance-advertising-funded models as potentially problematic. Unfettered engagement strategies bear significant and underappreciated costs that are endangering our privacy, our democracy, and our culture itself. It's time that wrongful engagement, and the asserted "free" business models it generates, started to bear the burden of those costs. [ABSTRACT FROM AUTHOR]

Geothermal heat flow is a key parameter in governing ice dynamics, via its influence on basal melt and sliding, englacial rheology, and erosion. It is expected to exhibit significant lateral variability across Antarctica. Despite this, surface heat flow derived from Earth's interior remains one of the most poorly constrained parameters controlling ice sheet evolution. To obtain a continent‐wide map of Antarctic heat supply at regional‐scale resolution, we estimate upper mantle thermomechanical structure directly from VS. Until now, direct inferences of Antarctic heat supply have assumed constant crustal composition. Here, we explore a range of crustal conductivity and radiogenic heat production values by fitting thermodynamically self‐consistent geotherms to their seismically inferred counterparts. Independent estimates of crustal conductivity derived from VP are integrated to break an observed trade‐off between crustal parameters, allowing us to infer Antarctic geothermal heat flow and its associated uncertainty. Plain Language Summary: The future evolution of the Antarctic Ice Sheet depends on its stability, which describes how sensitive it is to environmental change. A key factor influencing ice sheet stability is how much thermal energy is transferred into its base from Earth's interior: a parameter called geothermal heat flow. If the level of heat supply is high, melting at the base of the ice sheet is encouraged, resulting in enhanced sliding toward outlet glaciers at the continental perimeter. Consequently, ice loss is accelerated, and the likelihood of glacial collapse is increased. Therefore, an accurate map of Antarctic geothermal heat flow, including how this parameter varies from region to region, is needed to produce high quality projections of Antarctic ice mass loss and therefore global sea level change. In this study, we use models of how seismic wave speed varies within Earth to estimate its three‐dimensional temperature structure, as well as its thermal conductivity. These data are used to infer a collection of best‐fitting models of Earth's thermal state, and hence estimate Antarctic geothermal heat flow. Key Points: Demonstration of new methodology for inferring geothermal heat flow from seismological dataS‐ and P‐wave velocity used together to infer and fit geothermsIncorporation of laterally varying crustal conductivity and heat production [ABSTRACT FROM AUTHOR]

Although histone proteins are widely known for their intranuclear functions where they organize DNA, all five histone types can also be released into the extracellular space from damaged cells. Extracellular histones can interact with pattern recognition receptors of peripheral immune cells, including toll-like receptor 4 (TLR4), causing pro-inflammatory activation, which indicates they may act as damage-associated molecular patterns (DAMPs) in peripheral tissues. Very limited information is available about functions of extracellular histones in the central nervous system (CNS). To address this knowledge gap, we applied mixed histones (MH) to cultured cells modeling neurons, microglia, and astrocytes. Microglia are the professional CNS immunocytes, while astrocytes are the main support cells for neurons. Both these cell types are critical for neuroimmune responses and their dysregulated activity contributes to neurodegenerative diseases. We measured effects of extracellular MH on cell viability and select neuroimmune functions of microglia and astrocytes. MH were toxic to cultured primary murine neurons and also reduced viability of NSC-34 murine and SH-SY5Y human neuron-like cells in TLR4-dependent manner. MH did not affect the viability of resting or immune-stimulated BV-2 murine microglia or U118 MG human astrocytic cells. When applied to BV-2 cells, MH enhanced secretion of the potential neurotoxin glutamate, but did not modulate the release of nitric oxide (NO), tumor necrosis factor-α (TNF), C-X-C motif chemokine ligand 10 (CXCL10), or the overall cytotoxicity of lipopolysaccharide (LPS)- and/or interferon (IFN)-γ-stimulated BV-2 microglial cells towards NSC-34 neuron-like cells. We demonstrated, for the first time, that MH downregulated phagocytic activity of LPS-stimulated BV-2 microglia. However, MH also exhibited protective effect by ameliorating the cytotoxicity of LPS-stimulated U118 MG astrocytic cells towards SH-SY5Y neuron-like cells. Our data demonstrate extracellular MH could both damage neurons and alter neuroimmune functions of glial cells. These actions of MH could be targeted for treatment of neurodegenerative diseases. [ABSTRACT FROM AUTHOR]

Demographic histories are frequently a product of the environment, as populations expand or contract in response to major environmental changes, often driven by changes in climate. Meso‐ and bathy‐pelagic fishes inhabit some of the most temporally and spatially stable habitats on the planet. The stability of the deep‐pelagic could make deep‐pelagic fishes resistant to the demographic instability commonly reported in fish species inhabiting other marine habitats, however the demographic histories of deep‐pelagic fishes are unknown. We reconstructed the historical demography of 11 species of deep‐pelagic fishes using mitochondrial and nuclear DNA sequence data. We uncovered widespread evidence of population expansions in our study species, a counterintuitive result based on the nature of deep‐pelagic ecosystems. Frequency‐based methods detected potential demographic changes in nine species of fishes, while extended Bayesian skyline plots identified population expansions in four species. These results suggest that despite the relatively stable nature of the deep‐pelagic environment, the fishes that reside here have likely been impacted by past changes in climate. Further investigation is necessary to better understand how deep‐pelagic fishes, by far Earth's most abundant vertebrates, will respond to future climatic changes. [ABSTRACT FROM AUTHOR]

Background: The First Episode Rapid Early Intervention for Eating Disorders (FREED) service has been shown to reduce the wait for care and improve clinical outcomes in initial evaluations. These findings led to the national scaling of FREED in England. To support this scaling, we conducted a mixed method evaluation of the perceptions and experiences of clinicians in the early phases of scaling. The Normalisation Process Theory (NPT) was used as a conceptual lens to understand if and how FREED becomes embedded in routine practice. Methods: The convergent mixed method evaluation included 21 semi-structured interviews with clinicians from early adopter sites and 211 surveys administered to clinicians before, immediately after and 3 months after the FREED training. The interview guide and survey included questions evaluating attitudes towards early intervention for eating disorders (EDs) and NPT mechanisms. Interview data were analysed using an inductive thematic analysis. The NPT was applied to the inductively derived themes to evaluate if and how NPT domains impacted the implementation. Survey data were analysed using multilevel growth models. Results: Six themes and 15 subthemes captured barriers and facilitators to implementation at the patient, clinician, service, intervention, implementation and wider system levels. These interacted with the NPT mechanisms to facilitate or hinder the embedding of FREED. Overall, clinicians were enthusiastic and positive towards early intervention for EDs and FREED, largely because of the expectation of improved patient outcomes. This was a considerable driver in the uptake and implementation of FREED. Clinicians also had reservations about capacity and the potential impact on other patients, which, at times, was a barrier for its use. The FREED training led to significant improvements in positive attitudes and NPT mechanisms that were largely maintained at the 3-month follow-up. However, negative attitudes did not significantly improve following training. Conclusions: Positive attitudes towards early intervention for EDs increased enthusiasm and engagement with the model. Features of the model and its implementation were effective at developing adopter commitment and capabilities. However, there were aspects of the model and its implementation which require attention in the future (e.g., capacity and the potential impact on the wider service). Plain english summary: First Episode Rapid Early Intervention for Eating Disorders (FREED) is an early intervention service for 16-to-25-year-olds who have had an eating disorder (ED) for three years or less. Studies have shown that FREED can reduce the length of time that people wait for treatment and that it improves outcomes. However, it was unclear what it was like for clinicians trying to deliver the service. We used questionnaires and interviews with clinicians who were preparing to or already delivering FREED to understand what they thought about it and their experiences of delivering it. Overall, clinicians were positive and enthusiastic about early intervention for EDs and FREED because they believed that it could improve patient outcomes. This enthusiasm and features of the FREED model and support facilitated its delivery. However, clinicians were worried about their ability to deliver FREED with limited resources and the impact this might have on patients who are not eligible for the service. Resources were a major barrier to providing treatment as quickly as possible. This study suggests that FREED was well-received by those delivering it and that many parts of the service and support were helpful, but resource issues need to be addressed in the future. [ABSTRACT FROM AUTHOR]

Demographic histories are frequently a product of the environment, as populations expand or contract in response to major environmental changes, often driven by changes in climate. Meso‐ and bathy‐pelagic fishes inhabit some of the most temporally and spatially stable habitats on the planet. The stability of the deep‐pelagic could make deep‐pelagic fishes resistant to the demographic instability commonly reported in fish species inhabiting other marine habitats, however the demographic histories of deep‐pelagic fishes are unknown. We reconstructed the historical demography of 11 species of deep‐pelagic fishes using mitochondrial and nuclear DNA sequence data. We uncovered widespread evidence of population expansions in our study species, a counterintuitive result based on the nature of deep‐pelagic ecosystems. Frequency‐based methods detected potential demographic changes in nine species of fishes, while extended Bayesian skyline plots identified population expansions in four species. These results suggest that despite the relatively stable nature of the deep‐pelagic environment, the fishes that reside here have likely been impacted by past changes in climate. Further investigation is necessary to better understand how deep‐pelagic fishes, by far Earth's most abundant vertebrates, will respond to future climatic changes. [ABSTRACT FROM AUTHOR]

Church governance is not often debated within a philosophical or theological sphere. This is perhaps because church governance has been part of tradition since Constantine and the initial Greek philosophical world view of sovereignty and hierarchy. Such a stance has led towards a managerial mindset that follows and conforms to the world, which plays out within the Anglican polity in the setting of an adversarial parliamentary style synod. This style encourages bounded communities of power that often refute the burgeoning inspirations of the Spirit. In changing the underlying theological basis of such a stance, by invoking the understanding of an undeniable community in the singularity of the Triune God, governance becomes more open. Engaging with, primarily, Agamben but also others from philosophy, a new viewpoint is presented to challenge the manner through which tradition is wielded as the only possibility. In seeing through a differing lens, communities can be conceived as both porous and interconnected, thus allowing the body of Christ to respond with transformative action as opposed to a continuum of conformance with secular legality. In this manner, the bishop's role may become more centralised towards a Eucharistic one, as opposed to the managerial mindset and role, to enhance the possibilities of God's love. This then removes the need for a hierarchy driven by a sovereign mindset that tradition bolsters, whilst maintaining loving and authoritative oversight that tradition suggests. [ABSTRACT FROM AUTHOR]

Cellular aging is associated with dysfunction of numerous tissues affecting multiple organ systems. A striking example of this is related to age-related bone loss, or osteoporosis, increasing fracture incidence. Interestingly, the two compartments of bone, cortical and cancellous or trabecular, rely on different mechanisms for development and maintenance during 'normal' aging. At a cellular level, the aging process disturbs a multitude of intracellular pathways. In particular, alterations in cellular metabolic functions thereby impacting cellular bioenergetics have been implicated in multiple tissues. Therefore, this study aimed to characterize how metabolic processes were altered in bone forming osteoblasts in aged mice compared to young mice. Metabolic flux analyses demonstrated both stromal cells and mature, matrix secreting osteoblasts from aged mice exhibited mitochondrial dysfunction. This was also accompanied by a lack of adaptability or metabolic flexibility to utilize exogenous substrates compared to osteoblasts cultured from young mice. Additionally, lipid droplets accumulated in both early stromal cells and mature osteoblasts from aged mice, which was further depicted as increased lipid content within the bone cortex of aged mice. Global transcriptomic analysis of the bone further supported these metabolic data as enhanced oxidative stress genes were up-regulated in aged mice, while osteoblast-related genes were down-regulated when compared to the young mice. Collectively, these data suggest that aging results in altered osteoblast metabolic handling of both exogenous and endogenous substrates which could contribute to age-related osteoporosis. [ABSTRACT FROM AUTHOR]

Mammalian preimplantation embryos often contain chromosomal defects that arose in the first divisions after fertilization and affect a subpopulation of cells -- an event known as mosaic aneuploidy. In this issue of the JCI, Chavli et al. report single-cell genomic sequencing data for rigorous evaluation of the incidence and degree of mosaic aneuploidy in healthy human in vitro fertilization (IVF) embryos. Remarkably, mosaic aneuploidy occurred in at least 80% of human blastocyst-stage embryos, with often less than 20% of cells showing defects. These findings confirm that mosaic aneuploidy is prevalent in human embryos, indicating that the process is a widespread event that rarely has clinical consequences. There are major implications for preimplantation genetic testing of aneuploidy (PGT-A), a test commonly used to screen and select IVF embryos for transfer. The application and benefit of this technology is controversial, and the findings provide more cause for caution on its use. [ABSTRACT FROM AUTHOR]

Parelaphostrongylus tenuis causes ungulate morbidity and mortality in eastern and central North America, but no reference genome sequence exists to facilitate research. Here, we present a P. tenuis genome assembly and annotation, generated with PacBio and Illumina technologies. The assembly is 491 Mbp, with 7285 scaffolds and 185 kb N50. [ABSTRACT FROM AUTHOR]

The article discusses the need to create a national quarantine plan as part of a modernized public health strategy to a pandemic in the U.S. following the COVID-19 pandemic. Other topics include the statutory ability of the federal government to implement a national quarantine as a public health response to contagious diseases, and the challenges with the implementation of public health mandates involving quarantine.

Not meeting recommended A1C targets may be associated with postoperative complications in adults, but there are no studies reporting on the relationship between preoperative A1C and postoperative complications in children with type 1 or type 2 diabetes. The objective of this study was to determine whether elevated A1C levels were associated with an increased incidence of postoperative complications in children with diabetes presenting for elective noncardiac surgery or diagnostic procedures. It found no such association, suggesting no need to delay elective surgery in children with diabetes until A1C is optimized. [ABSTRACT FROM AUTHOR]

In the United States (US), salt marshes are especially vulnerable to the effects of projected sea level rise, increased storm frequency, and climatic changes. Sentinel-2 data offer the opportunity to observe the land surface at high spatial resolutions (10 m). The Sentinel-2 data, encompassing Cumberland Island National Seashore, Fort Pulaski National Monument, and Canaveral National Seashore, were analyzed to identify temporal changes in salt marsh presence from 2016 to 2020. ENVI-derived unsupervised and supervised classification algorithms were applied to determine the most appropriate procedure to measure distant areas of salt marsh increases and decreases. The Normalized Difference Vegetation Index (NDVI) was applied to describe the varied vegetation biomass spatially. The results from this approach indicate that the ENVI-derived maximum likelihood classification provides a statistical distribution and calculation of the probability (>90%) that the given pixels represented both water and salt marsh environments. The salt marshes captured by the maximum likelihood classification indicated an overall decrease in salt marsh area presence. The NDVI results displayed how the varied vegetation biomass was analogous to the occurrence of salt marsh changes. Areas representing the lowest NDVI values (−0.1 to 0.1) corresponded to bare soil areas where a salt marsh decrease was detected. [ABSTRACT FROM AUTHOR]

This study presents an experimental investigation into the cyclic performance of a new tube-in-tube buckling restrained brace (BRB) configuration. In this study, reduced- and large-scale brace geometries are tested to quantify inelastic hysteretic response, understand core confinement parameters, and determine the influence of end connection constraints. A total of 11 reduced-scale brace specimens are cyclically tested, along with three large-scale braces representing two core geometries and two core constraint configurations. Results from the reduced- and large-scale brace testing suggest that the tube-in-tube BRB configurations are capable of achieving the required inelastic capacity for qualification in AISC 341-16 specifications. All scaled specimens survived cumulative inelastic demands that exceeded 240 times the yield displacement (with several surviving more than 400 times the yield displacement). Results indicate that tube-in-tube BRBs are capable of producing stable tension-compression hysteretic behavior during cyclic loading. Measured β values for the large-scale Specimen G2 were lower than 1.06 for all deformation cycles at or below 9.2Δby , while measured β values for the large-scale Specimen G3 were lower than 1.07 for all cycles at or below 3.6Δby. The peak β value for Specimens G2 and G3 was 1.16 and occurred during the 15.3Δby and 7.1Δby cycles, respectively. [ABSTRACT FROM AUTHOR]

Purpose: To examine 1-year persistence with oral atypical antipsychotics (OAAPs) for Medicaid patients with schizophrenia and assess the association between OAAP persistence and hospital and emergency department (ED) resource utilization.Patients and Methods: Using 2016– 2020 multi-state Medicaid claims data, this retrospective study followed patients diagnosed with schizophrenia for 12 months after initiating OAAP therapy. Patients started on an OAAP with no evidence of antipsychotic use in the previous 6 months were included if they had a diagnosis of schizophrenia, were not dually enrolled in Medicaid and Medicare, did not switch to a long-acting injectable antipsychotic, and were continuously eligible 6 months before and 12 months after the initial OAAP prescription (index date). OAAP persistence was measured allowing for a < 60-day gap. All-cause and schizophrenia-related inpatient and emergency department (ED) resource utilization during the follow-up period were compared between OAAP persistent and non-persistent groups.Results: The study sample of 13,007 had an average age of 39.1 years and 57.0% were male. Patients were persistent with their index OAAP for 135 days on average and 73.1% had a ≥ 60-day gap in antipsychotic therapy post-index. While 32.8% and 28.6% of patients who did not persist with their index OAAP restarted the index OAAP or switched to a different OAAP medication later in the year, respectively, a larger proportion (38.6%) had no further OAAP prescriptions. After adjustment for demographic and clinical variables, compared to non-persistent patients, persisting with OAAPs was significantly associated with fewer all-cause and schizophrenia-related hospitalizations (Incidence Rate Ratio [IRR]=0.742, p< 0.001; IRR=0.823, p< 0.001; respectively) and ED visits (IRR=0.759, p< 0.001; IRR=0.773, p< 0.001; respectively).Conclusion: Non-persistence with OAAP medication is common among patients with schizophrenia and associated with negative outcomes including increased utilization of hospital and ED resources. Patient-centered interventions that improve antipsychotic persistence should be implemented to facilitate optimal outcomes in this population. [ABSTRACT FROM AUTHOR]

Species within the same ecological guild exhibit niche attributes that vary in association with their diet, spatial occupancy, and temporal activity to reduce competition. In the case of the tropical felid community, many species exhibit substantial overlap in these niche dimensions. Consequently, jaguars (Panthera onca) will sometimes kill the smaller ocelot (Leopardus pardalis) competitor in a phenomenon called intraguild predation (IGP), which is a major structuring force in tropical forests. We developed a spatially explicit agent-based model to understand IGP with the expectation that ocelots employ spatial avoidance strategies using available forest canopy as the more arboreal species. We parameterized model agents with realistic behaviors to replicate the real-world environment. Jaguar and ocelot agents were allowed to move, hunt, and reproduce with varying numbers, heights, and canopy thickness of trees as we recorded IGP events and ocelot canopy occupancy. We used structural equation modeling (SEM) to demonstrate how the number and height of trees significantly affected IGP occurrence. In accordance with our hypothesis, we found that the main contributor mediating coexistence between the two species was spatial avoidance of jaguars by ocelots by using available canopy refuges. Our modeling approach has broad application to different environments with similar intraguild interactions to predict the importance of forest structure and can inform policy directed toward forest management and habitat conservation. [ABSTRACT FROM AUTHOR]

The Mach number is the primary parameter in determining the intrinsic driving properties, and effect on the environment of a supersonic jet. In the most basic form, a jet is released when a wall of a large high-pressure gas reservoir is punctured. The resulting high-pressure jet contains a configuration of shocks that continue to disturb the environment after the initial bow shock has passed. Here, we perform numerical simulations to determine the properties attributable to pure adiabatic hydrodynamic effects, taking a uniform stream out of a circular nozzle. We take a range of Mach numbers that, along with the jet overpressure, determine the flow pattern and shock locations. We distinguish conditions that generate Mach shock discs rather than a diamond pattern of oblique regular reflections. Potential observational diagnostics explored include the disc size, the distance from the nozzle, and oscillations in shock positions. Rapid oscillations occur in the divergent–convergent pattern through a feedback/hysteresis effect promoted by the ambient medium. The underlying flow patterns are independent of relative jet density, but heavy jets display both lower amplitude and lower frequency oscillations. We also study the energy transferred into the environment. Overpressured jets may contribute to noise and sound wave generation through screeching. However, these oscillations in the near-field are not sufficiently significant to regulate star and galaxy formation. We expect that upcoming high dynamic range and resolution observations will increasingly detect the shock patterns as jet gas transits from protostellar and galactic cores. [ABSTRACT FROM AUTHOR]

An average shotgun proteomics experiment detects approximately 10,000 human proteins from a single sample. However, individual proteins are typically identified by peptide sequences representing a small fraction of their total amino acids. Hence, an average shotgun experiment fails to distinguish different protein variants and isoforms. Deeper proteome sequencing is therefore required for the global discovery of protein isoforms. Using six different human cell lines, six proteases, deep fractionation and three tandem mass spectrometry fragmentation methods, we identify a million unique peptides from 17,717 protein groups, with a median sequence coverage of approximately 80%. Direct comparison with RNA expression data provides evidence for the translation of most nonsynonymous variants. We have also hypothesized that undetected variants likely arise from mutation-induced protein instability. We further observe comparable detection rates for exon–exon junction peptides representing constitutive and alternative splicing events. Our dataset represents a resource for proteoform discovery and provides direct evidence that most frame-preserving alternatively spliced isoforms are translated. Deep proteome sequencing achieves ~80% coverage of the human proteome. [ABSTRACT FROM AUTHOR]

Background: Dermal fillers have created a multi‐billion‐dollar industry. They are the second most popular form of injectable, as they primarily address volume loss, augmentation, and provide immediate results. The most popular form includes hyaluronic acid‐based fillers, however, alternatives exist. Objective: To create clinical charts to help with filler selection, injection, and addressing common complications. Methods: The current literature and expert opinions form our two senior authors were used to create a numerical and color‐coded chart based on G‐prime for filler selection, as well as an anatomical table with current recommendations and pearls. We have also included a safety table with current clinical recommendation to deal with common filler‐related complications. Conclusion: Fillers are a safe and reliable method to achieve augmentation. Filler selection in various anatomical planes plays a significant role in achieving favorable results. [ABSTRACT FROM AUTHOR]

Plant growth is influenced by interactions with neighbouring plants. The strength and direction of the cumulative neighbourhood effect on growth can depend on neighbour properties, such as their abundance, size and proximity, as well as the degree of similarity between interacting plants and their traits, which can be captured by the species identity of neighbours. Such interactions are also influenced by the local environmental conditions that are largely determined by climate. Because neighbour and climatic effects are typically explored in isolation, particularly in long‐lived species such as trees, it is unclear how the impacts of neighbours on plant growth shift in response to temporal variation in climatic conditions.Here, we explored how neighbouring plants impact the annual growth of two eucalypts, Eucalyptus delegatensis and Eucalyptus regnans, over three growing seasons in an experimental forest in south‐east Tasmania, Australia. We assessed whether eucalypt growth rates could be described by the number, size, proximity, and species identity of neighbours, and how the strength of this effect was influenced by the growing season climatic conditions.We found that climate and neighbouring plants had an interactive impact on eucalypt growth. Neighbours had a consistent, competitive effect on the growth of both eucalypts in all three growing seasons which was strongly related to the cumulative neighbourhood biomass. The identity of neighbours was important in determining E. regnans growth only, whereby distinguishing neighbours according to functional group best described growth. Over all three growing seasons, we predicted that, on average, neighbours reduced E. delegatensis and E. regnans mean annual growth by 60.5% and 48.4%, respectively. However, the strength of the competitive effect of neighbours on eucalypt growth was related to growing season climate, being strongest when conditions were hot and dry and weakest in cool, wet conditions.Synthesis: Given the consistent results observed in two co‐occurring eucalypts, our findings suggest that drier and hotter climatic conditions increase the strength of competitive effects on tree growth. This has implications for future forest productivity given projected increased temperatures and variation in rainfall patterns globally. [ABSTRACT FROM AUTHOR]

Purpose: Feedback from service users is a valuable source for improving the quality of care and services, potentially reflecting the successes and failures in providing empowering healthcare. In supporting empowerment, the multidimensionality of knowledge of service users is assumed to be a crucial factor, yet feedback has not been explored from the perspective of empowering knowledge. In this study, the aim was to analyze the knowledge areas expressed in the service users' feedback from the point of view of empowering knowledge.Patients and Methods: This was a retrospective study utilizing systematically collected service-user feedback from a feedback register of one university hospital district in Finland. Free-form feedback (n = 26,374) along with structured evaluative feedback was given by the patients themselves or their significant others, either by text message or using a feedback form, in 2019. The content of the feedback was analyzed according to the empowering knowledge areas (biophysiological, cognitive, functional, experiential, ethical, social, and financial), quantified, and analyzed statistically in relation to the background characteristics of service users.Results: Service users gave multidimensional free-form feedback about the knowledge and educational practices in care and services. In the free-form feedback, the most common empowering knowledge areas were biophysiological and cognitive ones, whilst experiential, ethical, social, and financial areas were the least common. The highest ratings of structured evaluative feedback were associated with the cognitive and ethical areas.Conclusion: Register-based feedback is systematic data for quality evaluation. In this study, service users seem to actively evaluate the knowledge procession in care and services, and therefore, they can be actors involved in developing the quality of educational practices. It does, however, indicate a need to add multidimensionality and improve the quality of the knowledge, and by that, advance the potential of empowerment among diverse service users. [ABSTRACT FROM AUTHOR]

Nature provides numerous functions and services that can contribute to societal climate change adaptation. These 'adaptation services' can be sustained, latent, or novel, depend on persistence or transformation of ecosystems, and require varying co-production by people. Adaptation services also include climate mitigation. We present an approach to explore an extensive set of land use and climate scenarios that outline possible futures for a landscape, and quantify the contributions of adaptation services. We quantified adaptation success across six criteria relevant to the region, characterised the contributions of different types of adaptation services, and mapped spatial variation in contributions across the landscape. We built an integrated model of the Mackenzie District (an upland landscape of Aotearoa New Zealand), and analysed 1200 hypothetical scenarios for the period 2060–2070. We found many adaptation options, with 46% of scenarios meeting the criteria for successful adaptation. Four sustained, two latent and five novel services co-produced through financial input made diverse contributions to economic profit, profit resilience, climate change mitigation, climate risk adaptation, landscape cultural heritage and biodiversity. Successful adaptation scenarios were multifunctional, relying on alternative combinations of services allowed by spatial heterogeneity. By accounting for the numerous relationships between people and natural components within complex landscape systems, our advanced simulation approach can inform participatory pathway development by quantifying the potential for nature to contribute to future climate change adaptation. [ABSTRACT FROM AUTHOR]

Traditional understanding of the risk of progression from Mycobacterium tuberculosis (Mtb) infection to tuberculosis (TB) overlooks diverse presentations across a spectrum of disease. We developed a deterministic model of Mtb infection and minimal (pathological damage but not infectious), subclinical (infectious but no reported symptoms), and clinical (infectious and symptomatic) TB, informed by a rigorous evaluation of data from a systematic review of TB natural history. Using a Bayesian approach, we calibrated the model to data from historical cohorts that followed tuberculin-negative individuals to tuberculin conversion and TB, as well as data from cohorts that followed progression and regression between disease states, disease state prevalence ratios, disease duration, and mortality. We estimated incidence, pathways, and 10-y outcomes following Mtb infection for a simulated cohort. Then, 92.0% (95% uncertainty interval, UI, 91.4 to 92.5) of individuals self-cleared within 10 y of infection, while 7.9% (95% UI 7.4 to 8.5) progressed to TB. Of those, 68.6% (95% UI 65.4 to 72.0) developed infectious disease, and 33.2% (95% UI 29.9 to 36.4) progressed to clinical disease. While 98% of progression to minimal disease occurred within 2 y of infection, only 71% and 44% of subclinical and clinical disease, respectively, occurred within this period. Multiple progression pathways from infection were necessary to calibrate the model and 49.5% (95% UI 45.6 to 53.7) of those who developed infectious disease undulated between disease states. We identified heterogeneous pathways across disease states after Mtb infection, highlighting the need for clearly defined disease thresholds to inform more effective prevention and treatment efforts to end TB. [ABSTRACT FROM AUTHOR]

Background: Unplanned readmissions (URs) after colorectal surgery (CRS) are common, expensive, and result from failure to progress in postoperative recovery. These are considered preventable, although the true extent is yet to be defined. In addition, their successful prediction remains elusive due to significant heterogeneity in this field of research. This systematic review and meta-analysis of observational studies aimed to identify the clinically relevant predictors of UR after colorectal surgery. Methods: A systematic review was conducted using indexed sources (The Cochrane Database of Systematic Reviews, MEDLINE, and Embase) to search for published studies in English between 1996 and 2022. The search strategy returned 625 studies for screening of which, 150 were duplicates, and 305 were excluded for irrelevance. An additional 150 studies were excluded based on methodology and definition criteria. Twenty studies met the inclusion criteria and for the meta-analysis. Independent meta-extraction was conducted by multiple reviewers (JD & SR) in accordance with PRISMA guidelines. The primary outcome was defined as UR within 30 days of index discharge after colorectal surgery. Data were pooled using a random-effects model. Risk of bias was assessed using the Quality in Prognosis Studies tool. Results: The reported 30-day UR rate ranged from 6% to 22.8%. Increased comorbidity was the strongest preoperative risk factor for UR (OR 1.39, 95% CI 1.28–1.51). Stoma formation was the strongest operative risk factor (OR 1.54, 95% CI 1.38–1.72). The occurrence of postoperative complications was the strongest postoperative and overall risk factor for UR (OR 3.03, 95% CI 1.21–7.61). Conclusions: Increased comorbidity, stoma formation, and postoperative complications are clinically relevant predictors of UR after CRS. These risk factors are readily identifiable before discharge and serve as clinically relevant targets for readmission risk-reducing strategies. Successful readmission prediction may facilitate the efficient allocation of healthcare resources. [ABSTRACT FROM AUTHOR]

Background: The concept of fever appears frequently throughout human literature, music, and art, and it has even been studied scientifically. It is not unexpected to discover precise descriptions of febrile patients in early recorded history because fever is such a prevalent symptom of sickness. Material and Methods: Patients admitted to Department of General Medicine, Government Medical College, Ongole, Andhra Pradesh, India, will participate in this study. One hundred individuals with fever and low platelet counts will be prospectively collected. The participant ages ranged from 18 to 79, however this was not a restriction on the study. Fifty-eight men and forty-two women made up the 100 people diagnosed with fever and thrombocytopenia. Results: Only 14 people didn't make it, while 86 made full recoveries. Thirty of the 86 patients who made a full recovery were followed up on, and their platelet counts were within normal range once they were discharged. Twelve people died from septicemia and multi-organ failure syndrome, and two died from dengue fever, for a total of fourteen deaths. Conclusion: Thrombocytopenia, which often caused bleeding symptoms, shaped these febrile diseases. Spontaneous bleeding patients should be evaluated for disseminated intravascular coagulation. Malaria patients do not need platelet transfusions since their platelet counts recover quickly following treatment. [ABSTRACT FROM AUTHOR]

In this paper, we address the lack of a unified approach to understanding engineering practice by developing and presenting a taxonomy of common engineering activities. The taxonomy consists of 86 common engineering activities linked to 17 engineering competencies and the 11 International Engineering Alliance graduate attributes. The list of activities was developed using a six-step process, including multiple systematic literature searches and surveying engineers. The taxonomy provides a critical foundation for better understanding what engineers do, particularly in the Australian and New Zealand context. The taxonomy has potential utility in both engineering practice research and engineering education curriculum reform. [ABSTRACT FROM AUTHOR]

How do distinct species cofunction in symbiosis, despite conflicting interests? A new collection of articles explores emerging themes as researchers exploit modern research tools and new models to unravel how symbiotic interactions function and evolve. This editorial discusses a new collection of articles exploring emerging themes in symbiosis research, as researchers exploit modern research tools and new models to unravel how symbiotic interactions function and evolve. [ABSTRACT FROM AUTHOR]

The article discusses the HF-REVERT trial, which is the first trial to test the efficacy and safety of an antisense oligonucleotide (ASO) in heart failure (HF). The trial focuses on patients with reduced left ventricular ejection fraction (LVEF) after a myocardial infarction (MI). The ASO being tested, CDR132L, suppresses microRNA (miR)-132-3p, which is known to exacerbate adverse cardiac remodeling. The primary endpoint of the trial is the change in echocardiographic left ventricular end-systolic volume index at 6 months. The article highlights the potential of manipulating non-coding RNAs as a new therapeutic strategy for HF. [Extracted from the article]

OBJECTIVES: To estimate payments for the treatment of COVID-19 compared with that of influenza or viral pneumonia (IP), from the perspective of the US payer. STUDY DESIGN: Retrospective cohort analysis. METHODS: Patients with COVID-19 during the period from October 1, 2020, to February 1, 2021, or IP during the period from October 1, 2018, to February 1, 2019, in the IBM MarketScan databases were identified. The index was defined as the date of the first COVID-19 or IP diagnosis. Patients with COVID-19 were stratified by severity. Variables for all patients included demographics and comorbidities at the time of index and duration of disease. IP and COVID-19 cohorts were matched using propensity scores, and inflation-adjusted all-cause payments (ACP), and disease- specific payments (DSP) for IP vs COVID-19 were estimated using generalized linear models. RESULTS: Matched cohorts included 6332 Medicare (female, 58.5%; mean [SD] age, 75.3 [7.6] years), and 397,532 commercially insured patients (female, 57.6%; mean [SD] age, 34.7 [16.7] years). ACP and DSP were significantly higher in the COVID-19 cohort vs IP cohort. Payments for severe/critical COVID-19 were significantly greater than those for IP, with adjusted marginal incremental DSP and ACP of $24,852 (95% CI, $21,573-$28,132) and $50,325 (95% CI, $43,932-$56,718), respectively. IP was significantly less expensive than moderate COVID-19 for commercial payers but not Medicare. IP was more expensive than mild COVID-19 for all payers. CONCLUSIONS: Payments associated with severe/critical COVID-19 significantly exceeded those associated with IP. For Medicare, IP was more expensive than mild or moderate COVID-19. For commercial payers, IP was less expensive than moderate COVID-19 but more expensive than mild COVID-19. [ABSTRACT FROM AUTHOR]

A 400-m deep and 970 km long conductivity, temperature, depth section in the Northeast Pacific Ocean is decomposed into sound-speed variations associated with tilting isopycnals and ocean spice. The vertical distribution of sound-speed variance from these two processes shows significant fluctuations in the mixed layer (ML) and transition layer (TRL) below. Acoustic simulations at 400 and 1000 Hz are conducted with the decomposed fields to quantify their relative impact on upper ocean propagation for source locations in the ML and TRL. The low frequency simulations show that localized scattering processes dominate the propagation while higher frequencies experience more diffuse scattering. For propagation in the ML, spice generates the most loss while tilt can reduce loss when combined with spice. Statistics further show that energy can couple into and out of the ML duct depending on source depth and frequency. [ABSTRACT FROM AUTHOR]

Sea surface temperatures (SSTs) vary not only due to heat exchange across the air‐sea interface but also due to changes in effective heat capacity as primarily determined by mixed layer depth (MLD). Here, we investigate seasonal and regional characteristics of the contribution of MLD anomalies to the month‐to‐month variability of SST using observational datasets. First, we propose a metric called Flux Divergence Angle, which can quantify the relative contributions of surface heat fluxes and MLD anomalies to SST variability. Using this metric, we find that MLD anomalies tend to amplify SST anomalies in the extra‐tropics, especially in the eastern ocean basins, during spring and summer. In contrast, MLD anomalies tend to suppress SST anomalies in the eastern tropical Pacific during December‐January‐February. This paper provides the first global picture of the observed importance of MLD anomalies to the local SST variability. Plain Language Summary: Sea surface temperature (SST) is one of the important indicators as well as drivers of climate variability over the globe. SST varies not only due to changes in surface heat fluxes but also due to changes in effective heat capacity as mainly determined by mixed layer depth (MLD). However, the observed characteristics of the latter process associated with the MLD anomalies are limited. In this study, we propose a new metric called "Flux Divergence Angle (FDA)," which can quantify the relative importance of MLD and surface heat flux to the SST variability. Using this metric, we find that the MLD anomalies tend to amplify the local SST variability in the extra‐tropics during spring and summer. On the other hand, MLD anomalies tend to suppress the SST variability in the eastern tropical Pacific during December‐January‐February. This paper provides, for the first time, the global picture of relative importance of MLD anomalies to the SST variability based on observations. Key Points: Relative contributions of mixed layer depth (MLD) and surface heat flux anomalies to sea surface temperature (SST) variability are investigated using the Flux Divergence Angle metricMLD anomalies tend to amplify SST anomalies in the extra‐tropics, especially in eastern part of ocean basin, during the spring and summerMLD anomalies tend to suppress SST anomalies in the eastern tropical Pacific during December‐January‐February [ABSTRACT FROM AUTHOR]

Real-time adaptation is imperative to the control of robots operating in complex, dynamic environments. Adaptive control laws can endow even nonlinear systems with good trajectory tracking performance, provided that any uncertain dynamics terms are linearly parameterizable with known nonlinear features. However, it is often difficult to specify such features a priori, such as for aerodynamic disturbances on rotorcraft or interaction forces between a manipulator arm and various objects. In this paper, we turn to data-driven modeling with neural networks to learn, offline from past data, an adaptive controller with an internal parametric model of these nonlinear features. Our key insight is that we can better prepare the controller for deployment with control-oriented meta-learning of features in closed-loop simulation, rather than regression-oriented meta-learning of features to fit input-output data. Specifically, we meta-learn the adaptive controller with closed-loop tracking simulation as the base-learner and the average tracking error as the meta-objective. With both fully actuated and underactuated nonlinear planar rotorcraft subject to wind, we demonstrate that our adaptive controller outperforms other controllers trained with regression-oriented meta-learning when deployed in closed-loop for trajectory tracking control. [ABSTRACT FROM AUTHOR]

Multicopper active sites for small molecule activation in materials and enzymatic systems rely on controlled but adaptable coordination spheres about copper clusters for enabling challenging chemical transformations. To translate this constrained flexibility into molecular multicopper complexes, developments are needed in both ligand design for clusters and synthetic strategies for modifying the cluster cores. The present study investigates the chemistry of a class of pyridyldiimine-derived macrocycles with geometrically flexible aliphatic linkers of varying lengths (nPDI2, n = 2, 3). A series of dicopper complexes bound by the nPDI2 ligands are described and found to exhibit improved solubility over their parent analogs due to the incorporation of 4-tBu groups on the pyridyl units and the use of triflate counterions. The ensuing synthetic study investigated methods for introducing various bridging ligands (µ-X; X = F, Cl, Br, N3, NO2, OSiMe3, OH, OTf) between the two copper centers within the macrocycle-supported complexes. Traditional anion metathesis routes were unsuccessful, but the abstraction of bridging halides resulted in "open-core" complexes suitable for capturing various anions. The geometric flexibility of the nPDI2 macrocycles was reflected in the various solid-state geometries, Cu–Cu distances, and relative Cu coordination spheres on variation in the identity of the captured anion. [ABSTRACT FROM AUTHOR]

Marine macroalgae are important indicators of healthy nearshore groundwater dependent ecosystems (GDEs), which are emergent global conservation priorities. Submarine groundwater discharge (SGD) supports abundant native algal communities in GDEs via elevated but naturally derived nutrients. GDEs are threatened by anthropogenic nutrient inputs that pollute SGD above ambient levels, favoring invasive algae. Accordingly, this case study draws on the GDE conditions of Kona, Hawai'i where we evaluated daily photosynthetic production and growth for two macroalgae; a culturally valued native (Ulva lactuca) and an invasive (Hypnea musciformis). Manipulative experiments—devised to address future land-use, climate change, and water-use scenarios for Kona—tested algal responses under a natural range of SGD nutrient and salinity levels. Our analyses demonstrate that photosynthesis and growth in U. lactuca are optimal in low-salinity, high-nutrient waters, whereas productivity for H. musciformis appears limited to higher salinities despite elevated nutrient subsidies. These findings suggest that reductions in SGD via climate change decreases in rainfall or increased water-use from the aquifer may relax physiological constraints on H. musciformis. Collectively, this study reveals divergent physiologies of a native and an invasive macroalga to SGD and highlights the importance of maintaining SGD quantity and quality to protect nearshore GDEs. [ABSTRACT FROM AUTHOR]

Envenomation by the Indian ornamental tarantula (Poecilotheria regalis) is medically relevant to humans, both in its native India and worldwide, where they are kept as pets. Muscle-related symptoms such as cramps and pain are commonly reported in humans following envenomation by this species. There is no specific treatment, including antivenom, for its envenomation. Moreover, the scientific knowledge of the impact of this venom on skeletal muscle function is highly limited. Therefore, we carried out this study to better understand the myotoxic properties of Poecilotheria regalis venom by determining its effects in cultured myoblasts and in the tibialis anterior muscle in mice. While there was no effect found on undifferentiated myoblasts, the venom affected differentiated multinucleated myotubes resulting in the reduction of fusion and atrophy of myotubes. Similarly, intramuscular administration of this venom in the tibialis anterior muscle in mice resulted in extensive muscle damage on day 5. However, by day 10, the regeneration was evident, and the regeneration process continued until day 20. Nevertheless, some tissue abnormalities including reduced dystrophin expression and microthrombi presence were observed on day 20. Overall, this study demonstrates the ability of this venom to induce significant muscle damage and affect its regeneration in the early stages. These data provide novel mechanistic insights into this venom-induced muscle damage and guide future studies to isolate and characterise individual toxic component(s) that induce muscle damage and their significance in developing better therapeutics. [ABSTRACT FROM AUTHOR]

Simple Summary: The human species naturally judges whether other agents are nice or mean from a young age. Recent research has suggested that such social judgments are influenced by the way humans form attachment bonds with others. Given dogs' rich evolutionary history alongside humans, researchers have become interested in whether dogs make similar evaluations of human social interactions, for instance, by distinguishing between someone who is helpful or unhelpful. However, this concept, to date, has shown mixed results. In the present study, we explore whether dogs' attachment bonds impact their ability to form these judgments. Specifically, the present study sought to investigate whether dogs' attachment bonds to their owners could predict the extent to which they successfully evaluated unfamiliar humans who interacted with their owners. We found that dogs with stronger attachment bonds to their owners were more likely to prefer people who helped their owners but were no more likely to avoid people who refused to help their owners. These results suggest that, as in humans, a dog's attachment may impact the way that they evaluate potential social partners. Scholars have argued that social evaluation, the capacity to evaluate different potential social partners, is an important capacity not just for humans but for all cooperative species. Recent work has explored whether domesticated dogs share a human-like ability to evaluate others based on prosocial and antisocial actions toward third parties. To date, this work has shown mixed results, suggesting that individual differences may play a role in dogs' capacity to evaluate others. In the present study, we test whether attachment—an individual difference that affects human social evaluation performance—can explain the mixed pattern of social evaluation results observed in dogs. We first tested dogs on a social evaluation task in which an experimenter either helped or refused to help the dog's owner open a container. We then assessed dogs' attachment strength using a subset of the C-BARQ. We found that attachment was a statistically significant predictor of dogs' preference toward the prosocial actor but was not a predictor in antisocial or control conditions. This finding provides early evidence that attachment may drive positivity biases in dogs and that attachment might explain mixed results within canine social evaluation literature. [ABSTRACT FROM AUTHOR]

Parkinson's disease (PD) is a common movement disorder, estimated to affect 4% of individuals by the age of 80. Mutations in the glucocerebrosidase 1 (GBA1) gene represent the most common genetic risk factor for PD, with at least 7–10% of non-Ashkenazi PD individuals carrying a GBA1 mutation (PD-GBA1). Although similar to idiopathic PD, the clinical presentation of PD-GBA1 includes a slightly younger age of onset, a higher incidence of neuropsychiatric symptoms, and a tendency to earlier, more prevalent and more significant cognitive impairment. The pathophysiological mechanisms underlying PD-GBA1 are incompletely understood, but, as in idiopathic PD, α-synuclein accumulation is thought to play a key role. It has been hypothesized that this overexpression of α-synuclein is caused by epigenetic modifications. In this paper, we analyze DNA methylation levels at 17 CpG sites located within intron 1 and the promoter of the α-synuclein (SNCA) gene in three different brain regions (frontal cortex, putamen and substantia nigra) in idiopathic PD, PD-GBA1 and elderly non-PD controls. In all three brain regions we find a tendency towards a decrease in DNA methylation within an eight CpG region of intron 1 in both idiopathic PD and PD-GBA1. The trend towards a reduction in DNA methylation was more pronounced in PD-GBA1, with a significant decrease in the frontal cortex. This suggests that PD-GBA1 and idiopathic PD have distinct epigenetic profiles, and highlights the importance of separating idiopathic PD and PD-GBA1 cases. This work also provides initial evidence that different genetic subtypes might exist within PD, each characterized by its own pathological mechanism. This may have important implications for how PD is diagnosed and treated. [ABSTRACT FROM AUTHOR]

Timber heritage faces numerous risks, with the threat from insect and fungal attack particularly sensitive to climate. The Scheffer index estimates the deterioration of wood by combining average temperature and days of rain. We determined the Scheffer index from twenty sites in Europe across the 20th and early 21st century using meteorological observations, largely from the European Climate Assessment Dataset. Results showed that Scheffer indices across Europe loosely align with Köppen climate classes, which are also defined in terms of temperature and rainfall. However, within a given Köppen class, a wide range of Scheffer indices were found, thus representing very different threats to heritage. This suggests that specific heritage climate parameters, such as the Scheffer index, are needed. Trends in the Scheffer index provide a fairly robust guide to management strategy by identifying locations where the risk for timber is increasing. However, a simple index cannot necessarily describe the complex interactions between biological pests and climate; such complexity is better handled with well-constructed models. Nevertheless, the Scheffer index offers heritage managers an easily calculated estimate of the spatial distribution of risk to timber and the likely direction of future change. [ABSTRACT FROM AUTHOR]