Search

Abstract Large predator attacks on humans often provoke calls for animal population reduction, assuming it will reduce such incidents. Whilst this seems logical, there is currently little evidence supporting a consistent link between large predator density and attacks on humans. Here, we assessed whether large predator density is linked to the frequency of attacks on humans using estuarine crocodile (Crocodylus porosus) data in the Northern Territory (NT), Australia. Over the past 50 years, the estuarine crocodile population in the NT has grown from a few thousand to over 100,000 non‐hatchling individuals. Crocodile and human population densities have been closely monitored throughout this period, allowing the frequency of attacks on humans to be assessed over a wide range of densities for both populations. Our analysis showed an increase in the frequency of attacks on humans as the crocodile population recovered from very low levels in the 1970s. However, the attack rates stabilised around 2009, despite crocodile density and the human population continuing to increase. Based on the relationship between crocodile density and human‐attack frequency, scenario modelling suggested that the crocodile population would need to be culled to a critically endangered level (e.g. 90% population reduction) to reduce attacks on humans from 2.16 to 1.16 attacks per year. We conclude that whilst crocodile density significantly influences crocodile attack rates at low crocodile population sizes, this relationship becomes weaker as the density increases. For estuarine crocodiles in the NT, a plateauing of attack risk occurred once crocodile density attained ~2 crocodiles per km of river, and we argue that this was because high crocodile densities instigated management (e.g. removal of bold animals, exclusion zones) and education initiates by the government (e.g. ‘Be crocwise’ campaign) that subsequently evoked a change in human behaviour around waterways and stabilised the attack rate. Read the free Plain Language Summary for this article on the Journal blog.

Bold behaviour of non-native species is hypothesized to facilitate invasion success, yet extreme boldness in wild and domesticated animals can be maladaptive. The purpose of this study was to compare individual behaviour among Australian native hatchery-reared (n = 33) and wild (n = 38) Murray cod (Maccullochella peelii) with invasive common carp (Cyprinus carpio; n = 30). Three laboratory tests measured individual behaviour: (1) emergence from a shelter, (2) exploration of a novel environment, and (3) approaching a predator. Wild invasive carp and hatchery-reared cod were generally faster and more likely to emerge and explore novel environments when compared with wild Murray cod. The ‘bold-type’ behaviours of hatchery-reared native cod were more like invasive carp than they were to ‘shy-type’ wild conspecifics, yet an important difference was that hatchery-reared cod spent substantially more time near a large predator while carp rapidly escaped. We suggest that these results are consistent with a bold-type invasion syndrome in invasive carp and learned boldness of hatchery-reared Murray cod. The propensity of invasive carp to rapidly explore and enter new environments, along with a fast predator escape response may have been important to their invasion success, while extreme risk-taking and predator naivety of hatchery-reared Murray cod may exacerbate post-release mortality rates in fisheries and conservation stocking programmes.

The silver perch, Bidyanus bidyanus (Mitchell) (Terapontidae) is a freshwater fish, endemic to the Murray-Darling river system in south-eastern Australia. Population declines have led to the fish being listed as critically endangered by the Australian Government. Knowledge about parasites and diseases of wild populations of freshwater fish are limited in Australia. During an examination of wild-caught silver perch, digenean mesocercaria were observed in the head tissues. A total of five of the 11 silver perch collected from the Wakool River, New South Wales, were infected with mesocercaria. All mesocercaria were found in the head tissues; no mesocercaria were found encysted in the eye lens. The mesocercaria were found to belong to the family Strigeidae based on the sequences of their internal transcribed spacer (ITS) region. The lack of comparable sequences of strigeid digeneans from Australian hosts precludes being able to determine if the mesocercaria found in this study are a new species or representatives of an already described species. However, genetic results confirm that this is a different species to other digeneans previously described from silver perch, thus increasing the number of digeneans reported from B. bidyanus to three species. The presence of digenean mesocercaria in the head tissues of a wild population of silver perch, as found in the present study, is of potential conservation significance. Given the critically endangered conservation status of B. bidyanus, and previous evidence of strigeid infection altering fish behaviour, ecology, and predation mortality, further research on the potential impacts of infection on wild populations is warranted.

Introduction Despite decades of brain MRI research demonstrating atypical neuroanatomical substrate in patients with autism spectrum disorder (ASD), it remains unclear whether and to what extent disorder-selective neuroanatomical abnormalities occur in this spectrum. This, and the fact that multiple brain disorders report a common neuroanatomical substrate, makes transference and the application of neuroimaging findings into the clinical setting an open challenge. Objectives To investigate the selective neuroanatomical alteration profile of the ASD brain, we employed a meta-analytic, data-driven, and reverse inference-based approach (i.e.; Bayes fACtor mOdeliNg). Methods Eligible voxel-based morphometry data were extracted by a standardized search on BrainMap and MEDLINE databases (849 published experiments, 131 brain disorders, 22747 clinical subjects, 16572 x-y-z coordinates). Two distinct datasets were generated: the ASD dataset, composed of ASD-related data; and the non-ASD dataset, composed of all other clinical conditions data. Starting from the two unthresholded activation likelihood estimation (ALE) maps, the calculus of the Bayes fACtor mOdeliNg was performed. This allowed us to obtain posterior probability distributions on the evidence of brain alteration specificity in ASD. Results We revealed both cortical and cerebellar areas of neuroanatomical alteration selectivity in ASD. Eight clusters showed a selectivity value ≥ 90%, namely the bilateral precuneus, the right inferior occipital gyrus, left lobule IX, left Crus II, right Crus I, and the right lobule VIIIA (Fig. 1). Conclusions The identification of this neuroanatomical pattern provides new insights into the complex pathophysiology of ASD, opening attractive prospects for future neuroimaging-based interventions. Disclosure No significant relationships.

Introduction When the Criminal Court Judge applies probation, the offender is entrusted to social assistants for the necessary observation, treatment and support. This case study examines the probation of a young man with high-functioning autistic traits, personality disorder and legal/illegal substance abuse. This young man, who arrived only in adulthood to a diagnosis of autistic traits, is aware only that is non-neurotypical. He does not recognize that he needs treatment for personality disorder, alcohol, substance and drug abuse. He faces a sentence of more than three years in prison but the Judge suspends the criminal trial. Objectives Clarify the relationship between high functioning autistic traits, comorbidity with personality disorder and drugs/substance abuse, and crimes committed; also describe the orientation of the Judge and what difficulties arise during the probation. Methods Examination of the criminal file and medical documents of the offender, known by social and health services. Results The offender correlates the crimes and its frailty with autism and not with antisocial behaviours to gain economic benefits from drug dealing. Conclusions The deficit in the social communication and lack of empathy for child victimes, for example, limits the effectiveness of probation. The probation, for a young with high-functioning autistic traits and comorbidity, does not seem to give satisfactory results in terms of rehabilitation and social integration, nor does it produce the extinction of crime.

No abstract available.

One of the best known crustacean hormones is the crustacean hyperglycemic hormone (CHH). However, the mechanisms involved in hormone release in these animals are poorly understood, and thus constitute the central objective of the present study. Different groups of crustaceans belonging to diverse taxa (Chasmagnathus granulata, a grapsid crab and Orconectes limosus, an astacid) were injected with serotonin, fluoxetine, or a mixture of both, and glycemic values (C. granulata and O. limosus) and CHH levels (O. limosus) were determined after 2 h in either submerged animals or animals exposed to atmospheric air. Both serotonin and fluoxetine caused significant hyperglycemia (P

A halo generation mechanism in the nonperiodic lattices such as the SNS (Spallation Neutron Source) linac MEBT [medium-energy beam transport between radio-frequency quadrupole and DTL (drift tube linac)] is reported. We find that the nonlinear space charge force resulting from large transverse beam eccentricity ∼2:1 in the ∼1.6 m-long MEBT chopper section is responsible for halo formation. As a result, the beam distribution, based on the front end emittance measurements and multiparticle simulation studies, develops halo that leads to beam loss and radioactivation of the SNS linac. Designing lattices with transverse beam eccentricity close to 1:1 suppresses this kind of halo generation. Modifying the MEBT optics and introducing adjustable collimators in the MEBT significantly reduced beam losses in the coupled cavity linac, which is a preferred scheme for mitigating halo. It turns out that the DTL collimation does not effectively remove halo and presents a risk of overheating drift tubes.

Abstract Background Recent research has shown the mental health consequence of social distancing during the COVID-19 pandemic, but longitudinal data are relatively scarce. It is unclear whether the pattern of isolation and elevated stress seen at the beginning of the pandemic persists over time. This study evaluates change in social interaction over six months and its impact on emotional wellbeing among older adults. Methods We drew data from a panel study with six repeated assessments of social interaction and emotional wellbeing conducted monthly May through October 2020. The sample included a total of 380 White, Black and Hispanic participants aged 50 and over, of whom 33% had low income, who residing in fourteen U.S. states with active stay-at-home orders in May 2020. The analysis examined how change in living arrangement, in-person interaction outside the household, quality of relationship with family and friends, and perceived social support affected trajectories of isolation stress, COVID worry and sadness. Results While their living arrangements (Odds Ratio [OR] = 0.95, 95% Confidence Interval [CI] = 0.87, 1.03) and relationship quality (OR = 0.94, 95% CI = 0.82, 1.01) remained stable, older adults experienced fluctuations in perceived social support (linear Slope b = -1.42, s.e. = 0.16, p

Mishra et al. have generated mice with a single amino acid substitution in BRCA2, which disrupts its interaction with DSS1 resulting in a severe HR defect. They show the interaction to be dispensable for HR at replication induced and meiotic DSBs.

Abstract Gradient Forest (GF) is a machine learning algorithm designed to analyze spatial patterns of biodiversity as a function of environmental gradients. An offset measure between the GF‐predicted environmental association of adapted alleles and a new environment (GF Offset) is increasingly being used to predict the loss of environmentally adapted alleles under rapid environmental change, but remains mostly untested for this purpose. Here, we explore the robustness of GF Offset to assumption violations, and its relationship to measures of fitness, using SLiM simulations with explicit genome architecture and a spatial metapopulation. We evaluate measures of GF Offset in: (1) a neutral model with no environmental adaptation; (2) a monogenic “population genetic” model with a single environmentally adapted locus; and (3) a polygenic “quantitative genetic” model with two adaptive traits, each adapting to a different environment. We found GF Offset to be broadly correlated with fitness offsets under both single locus and polygenic architectures. However, neutral demography, genomic architecture, and the nature of the adaptive environment can all confound relationships between GF Offset and fitness. GF Offset is a promising tool, but it is important to understand its limitations and underlying assumptions, especially when used in the context of predicting maladaptation.

Large predator attacks on humans often provoke calls for animal population reduction, assuming it will reduce such incidents. Whilst this seems logical, there is currently little evidence supporting a consistent link between large predator density and attacks on humans.Here, we assessed whether large predator density is linked to the frequency of attacks on humans using estuarine crocodile (Crocodylus porosus) data in the Northern Territory (NT), Australia. Over the past 50 years, the estuarine crocodile population in the NT has grown from a few thousand to over 100,000 non‐hatchling individuals. Crocodile and human population densities have been closely monitored throughout this period, allowing the frequency of attacks on humans to be assessed over a wide range of densities for both populations.Our analysis showed an increase in the frequency of attacks on humans as the crocodile population recovered from very low levels in the 1970s. However, the attack rates stabilised around 2009, despite crocodile density and the human population continuing to increase. Based on the relationship between crocodile density and human‐attack frequency, scenario modelling suggested that the crocodile population would need to be culled to a critically endangered level (e.g. 90% population reduction) to reduce attacks on humans from 2.16 to 1.16 attacks per year.We conclude that whilst crocodile density significantly influences crocodile attack rates at low crocodile population sizes, this relationship becomes weaker as the density increases. For estuarine crocodiles in the NT, a plateauing of attack risk occurred once crocodile density attained ~2 crocodiles per km of river, and we argue that this was because high crocodile densities instigated management (e.g. removal of bold animals, exclusion zones) and education initiates by the government (e.g. 'Be crocwise' campaign) that subsequently evoked a change in human behaviour around waterways and stabilised the attack rate. Read the free Plain Language Summary for this article on the Journal blog. Read the free Plain Language Summary for this article on the Journal blog. [ABSTRACT FROM AUTHOR]

Controversy surrounds the cellular role of the Bcl-2 family protein Bok. On one hand, it has been shown that all endogenous Bok is bound to inositol 1,4,5-trisphosphate receptors (IP3Rs), while other data suggest that Bok can act as a pro-apoptotic mitochondrial outer membrane permeabilization mediator, apparently kept at very low and non-apoptotic levels by efficient proteasome-mediated degradation. Here we show that 1) endogenous Bok is expressed at readily-detectable levels in key cultured cells (e.g., mouse embryonic fibroblasts and HCT116 cells) and is not constitutively degraded by the proteasome, 2) proteasome inhibitor-induced apoptosis is not mediated by Bok, 3) endogenous Bok expression level is critically dependent on the presence of IP3Rs, 4) endogenous Bok is rapidly degraded by the ubiquitin-proteasome pathway in the absence of IP3Rs at the endoplasmic reticulum membrane, and 5) charged residues in the transmembrane region of Bok affect its stability, ability to interact with Mcl-1, and pro-apoptotic activity when over-expressed. Overall, these data indicate that endogenous Bok levels are not governed by proteasomal activity (except when IP3Rs are deleted) and that while endogenous Bok plays little or no role in apoptotic signaling, exogenous Bok can mediate apoptosis in a manner dependent on its transmembrane domain.

L'auteur discute le rapport entre le débat allemand sur le Développement Durable et le concept sociologique d'une «société du risque». La discussion allemande sur le développement durable a tendance à ignorer les questions du risque. Ainsi, eile risque de ne faire que prolonger les dynamiques bien connues de la modernisation traditionnelle. La première partie du texte dresse un bilan critique du débat sur la durabilité à l'échelle nationale et locale. L'idée de durabilité est une idée régulatrice et directrice qui comprend aussi bien des chances que des problèmes. Les concepts sociologiques d'une société du risque (qui signifie «société des dangers») et de la modernisation réflexive indiquent que le savoir scientifique a tendance à perdre l'unanimité qui lui fut attribuée dans la société moderne. II s'agit là d'un point central pour la base des connaissances scientifiques en matière de stratégies de durabilité. Cet argument est développé à travers la discussion de trois points d'ancrage possible d'une «politique des fictions de savoir», c'est-à-dire des dispositifs qui permettraient à la société de s'arranger avec l'incertitude des connaissances scientifiques.

Summary:. Wound healing problems are a major cause of morbidity for gender-affirming surgery (GAS) patients. Prior studies have shown sex differences in wound healing may exist. We hypothesized exogenous testosterone supplementation may impair post-GAS wound healing and developed a model to investigate this phenomenon. Mice were randomized by hormone regimen and gonadectomy (OVX). Gonadectomy or sham occurred on day 0 and mice were assigned to no testosterone (-T), mono- or bi-weekly (T/2T) testosterone groups. Dorsal splinted wounding occurred on day 14 and harvest on day 21. Serum testosterone levels were quantified with mass spectrometry. Tissue underwent analysis with planimetry, qPCR, ELISA, and immunofluorescence. Mean testosterone trough levels for bi-weekly regimen were higher compared to mono-weekly (397 versus 272 ng/dL; P = 0.027). At POD5, 2T injections led to 24.9% and 24.7% increases in mean wound size relative to SHAM and OVX/-T, respectively (P = 0.004; 0.001). Wounds in OVX/+2T mice demonstrated increased gene expression for inflammatory cytokines and macrophage marker F4/80 (P < 0.05). ELISA confirmed elevated wound TNFα levels (P < 0.05). Quantitative multiplex immunofluorescence with F4/80/NOS2/ARG1 showed significant increases in macrophage prevalence in OVX/+2T (P < 0.05). We developed a novel model of GAS hormonal milieu to study effects of exogenous testosterone on wound healing. Optimized twice-weekly dosing yielded serum levels comparable to clinical therapy. We showed exogenous testosterone administered to XX/OVX mice significantly impairs wound healing. A hyperinflammatory wound environment results in increased macrophage proliferation and elevated cytokines. Future efforts are directed toward mechanistic investigation and clinical validation.

Adult mammalian hematopoiesis is a dynamic cellular process that provides a continuous supply of myeloid, lymphoid, erythroid/megakaryocyte cells for host survival. This process is sustained by regulating hematopoietic stem cells (HSCs) quiescence, proliferation and activation under homeostasis and stress, and regulating the proliferation and differentiation of downstream multipotent progenitor (MPP) and more committed progenitor cells. Inhibitor of DNA binding (ID) proteins are small helix-loop-helix (HLH) proteins that lack a basic (b) DNA binding domain present in other family members, and function as dominant-negative regulators of other bHLH proteins (E proteins) by inhibiting their transcriptional activity. ID proteins are required for normal T cell, B cell, NK and innate lymphoid cells, dendritic cell, and myeloid cell differentiation and development. However, recent evidence suggests that ID proteins are important regulators of normal and leukemic hematopoietic stem and progenitor cells (HSPCs). This chapter will review our current understanding of the function of ID proteins in HSPC development and highlight future areas of scientific investigation.

Defining mechanism(s) that maintain tissue stem quiescence is important for improving tissue regeneration, cell therapies, aging, and cancer. We report here that genetic ablation of Id2 in adult hematopoietic stem cells (HSCs) promotes increased HSC activation and differentiation, which results in HSC exhaustion and bone marrow failure over time. Id2Δ/Δ HSCs showed increased cycling, ROS production, mitochondrial activation, ATP production, and DNA damage compared with Id2+/+ HSCs, supporting the conclusion that Id2Δ/Δ HSCs are less quiescent. Mechanistically, HIF-1α expression was decreased in Id2Δ/Δ HSCs, and stabilization of HIF-1α in Id2Δ/Δ HSCs restored HSC quiescence and rescued HSC exhaustion. Inhibitor of DNA binding 2 (ID2) promoted HIF-1α expression by binding to the von Hippel-Lindau (VHL) protein and interfering with proteasomal degradation of HIF-1α. HIF-1α promoted Id2 expression and enforced a positive feedback loop between ID2 and HIF-1α to maintain HSC quiescence. Thus, sustained ID2 expression could protect HSCs during stress and improve HSC expansion for gene editing and cell therapies.

Societal perceptions of river floods are typically negative because of the death and destruction they may cause, although scientists and natural resource managers have long recognized the critical ecological role of floods. Like fire and some other ecological disturbances, river flooding intersects many aspects of ecology and society. But unlike fire, flooding receives relatively little attention in the disturbance ecology literature. We call for more focused recognition of flood ecology as a discipline to help river science better inform societal perceptions through developing a better understanding of the ecological roles of flooding. We contend that the absence of a discipline of flood ecology has constrained progress in our understanding of how rivers function and that a formal conceptualization could help reveal the positive aspects of flooding. Finally, we propose a series of questions that we believe a discipline of flood ecology should address. [ABSTRACT FROM AUTHOR]

POGZ is an autism spectrum disorder risk gene. How POGZ mutations result in ASD is unclear and animal models are lacking. Here, the authors generate a brain specific Pogz deficient mouse presenting ASD-like behaviour and show the effects of Pogz deficiency in the cerebellum.

Severe injuries, such as burns, provoke a systemic inflammatory response syndrome (SIRS) that imposes pathology on all organs. Simultaneously, severe injury also elicits activation of the fibrinolytic protease plasmin. While the principal adverse outcome of plasmin activation in severe injury is compromised hemostasis, plasmin also possesses proinflammatory properties. We hypothesized that, following a severe injury, early activation of plasmin drives SIRS. Plasmin activation was measured and related to injury severity, SIRS, coagulopathy, and outcomes prospectively in burn patients who are not at risk of hemorrhage. Patients exhibited early, significant activation of plasmin that correlated with burn severity, cytokines, coagulopathy, and death. Burn with a concomitant, remote muscle injury was employed in mice to determine the role of plasmin in the cytokine storm and inflammatory cascades in injured tissue distant from the burn injury. Genetic and pharmacologic inhibition of plasmin reduced the burn-induced cytokine storm and inflammatory signaling in injured tissue. These findings demonstrate (a) that severe injury–induced plasmin activation is a key pathologic component of the SIRS-driven cytokine storm and SIRS-activated inflammatory cascades in tissues distant from the inciting injury and (b) that targeted inhibition of plasmin activation may be effective for limiting both hemorrhage and tissue-damaging inflammation following injury.

Social bots – partially or fully automated accounts on social media platforms – have not only been widely discussed, but have also entered political, media and research agendas. However, bot detection is not an exact science. Quantitative estimates of bot prevalence vary considerably and comparative research is rare. We show that findings on the prevalence and activity of bots on Twitter depend strongly on the methods used to identify automated accounts. We search for bots in political discourses on Twitter, using three different bot detection methods: Botometer, Tweetbotornot and “heavy automation”. We drew a sample of 122,884 unique user Twitter accounts that had produced 263,821 tweets contributing to five political discourses in five Western democracies. While all three bot detection methods classified accounts as bots in all our cases, the comparison shows that the three approaches produce very different results. We discuss why neither manual validation nor triangulation resolves the basic problems, and conclude that social scientists studying the influence of social bots on (political) communication and discourse dynamics should be careful with easy-to-use methods, and consider interdisciplinary research.

Abstract Inbreeding and enemy infestation are common in plants and can synergistically reduce their performance. This inbreeding ×environment (I × E) interaction may be of particular importance for the success of plant invasions if introduced populations experience a release from attack by natural enemies relative to their native conspecifics. Here, we investigate whether inbreeding affects plant infestation damage, whether inbreeding depression in growth and reproduction is mitigated by enemy release, and whether this effect is more pronounced in invasive than native plant populations. We used the invader Silene latifolia and its natural enemies as a study system. We performed two generations of experimental out‐ and inbreeding within eight native (European) and eight invasive (North American) populations under controlled conditions using field‐collected seeds. Subsequently, we exposed the offspring to an enemy exclusion and inclusion treatment in a common garden in the species’ native range to assess the interactive effects of population origin (range), breeding treatment, and enemy treatment on infestation damage, growth, and reproduction. Inbreeding increased flower and leaf infestation damage in plants from both ranges, but had opposing effects on fruit damage in native versus invasive plants. Inbreeding significantly reduced plant fitness; whereby, inbreeding depression in fruit number was higher in enemy inclusions than exclusions. This effect was equally pronounced in populations from both distribution ranges. Moreover, the magnitude of inbreeding depression in fruit number was lower in invasive than native populations. These results support that inbreeding has the potential to reduce plant defenses in S. latifolia, which magnifies inbreeding depression in the presence of enemies. However, future studies are necessary to further explore whether enemy release in the invaded habitat has actually decreased inbreeding depression and thus facilitated the persistence of inbred founder populations and invasion success.

Objective: Brown adipose tissue (BAT) is specialized in thermogenesis. The conversion of energy into heat in brown adipocytes proceeds via stimulation of β-adrenergic receptor (βAR)-dependent signaling and activation of mitochondrial uncoupling protein 1 (UCP1). We have previously demonstrated a functional role for pannexin-1 (Panx1) channels in white adipose tissue; however, it is not known whether Panx1 channels play a role in the regulation of brown adipocyte function. Here, we tested the hypothesis that Panx1 channels are involved in brown adipocyte activation and thermogenesis. Methods: In an immortalized brown pre-adipocytes cell line, Panx1 currents were measured using patch-clamp electrophysiology. Flow cytometry was used for assessment of dye uptake and luminescence assays for adenosine triphosphate (ATP) release, and cellular temperature measurement was performed using a ratiometric fluorescence thermometer. We used RNA interference and expression plasmids to manipulate expression of wild-type and mutant Panx1. We used previously described adipocyte-specific Panx1 knockout mice (Panx1Adip-/-) and generated brown adipocyte-specific Panx1 knockout mice (Panx1BAT-/-) to study pharmacological or cold-induced thermogenesis. Glucose uptake into brown adipose tissue was quantified by positron emission tomography (PET) analysis of 18F-fluorodeoxyglucose (18F-FDG) content. BAT temperature was measured using an implantable telemetric temperature probe. Results: In brown adipocytes, Panx1 channel activity was induced either by apoptosis-dependent caspase activation or by β3AR stimulation via a novel mechanism that involves Gβγ subunit binding to Panx1. Inactivation of Panx1 channels in cultured brown adipocytes resulted in inhibition of β3AR-induced lipolysis, UCP-1 expression, and cellular thermogenesis. In mice, adiponectin-Cre-dependent genetic deletion of Panx1 in all adipose tissue depots resulted in defective β3AR agonist- or cold-induced thermogenesis in BAT and suppressed beigeing of white adipose tissue. UCP1-Cre-dependent Panx1 deletion specifically in brown adipocytes reduced the capacity for adaptive thermogenesis without affecting beigeing of white adipose tissue and aggravated diet-induced obesity and insulin resistance. Conclusions: These data demonstrate that Gβγ-dependent Panx1 channel activation is involved in β3AR-induced thermogenic regulation in brown adipocytes. Identification of Panx1 channels in BAT as novel thermo-regulatory elements downstream of β3AR activation may have therapeutic implications.

The biomass of organisms of different sizes is increasingly being used to explore macroscale variation in food-web and community structure. Here we examine how invasive species and river flow regulation affect native fish biomass and fish community [log.sub.10] biomass--body mass scaling relationships in Australia's largest river system, the Murray-Darling. The [log.sub.10] biomass--body mass scaling exponent (scaling B) of invasive fishes (95% CI: -0.14 to -0.18) was less negative than for native fishes (95% CI: -0.20 to -0.25), meaning that invasive species attained a higher biomass in larger size-classes compared to native species. Flow alteration and invasive common carp (Cyprinus carpio) biomass were correlated with severe reductions in native fish biomass ranging from -47% to -68% (95% CI). Our study provides novel evidence suggesting that invasive and native communities have different biomass--body mass scaling patterns, which likely depend on differences in their trophic ecology and body size distributions. Our results suggest that restoration efforts using environmental flows and common carp control has potential to boost native fish biomass to more than double the current level.La biomasse d'organismes de differentes tailles est de plus en plus utilisee pour etudier les variations a echelle macroscopique de la structure des reseaux trophiques et des communautes. Nous examinons l'incidence d'especes envahissantes et de la regularisation du debit des rivieres sur la biomasse de poissons indigenes et les relations [log.sub.10] biomasse--masse corporelle pour les communautes de poissons dans le plus grand reseau hydrographique d'Australie, celui de Murray- Darling. L'exposant de la relation [log.sub.10] biomasse--masse corporelle (<>) de poissons envahissants (IC de 95 % : -0,14 a -0,18) est moins negatif que pour les poissons indigenes (IC de 95 %: -0,20 a -0,25), ce qui signifie que les especes envahissantes atteignent une plus grande biomasse dans les classes de plus grande taille que les especes indigenes. La modification du debit et la biomasse de carpes communes (Cyprinus carpio) envahissantes sont correlees a des baisses importantes de la biomasse de poissons indigenes allant de -47 % a -68 % (CI de 95 %). Notre etude fournit de nouvelles donnees qui donnent a penser que les communautes d'especes envahissantes et indigenes presentent differents motifs de relations entre la biomasse et la masse corporelle, qui dependent vraisemblablement de differences de leur ecologie trophique et de leurs repartitions des tailles du corps. Nos resultats indiqueraient que les efforts de restauration faisant appel aux debits environnementaux et au controle des carpes communes pourraient permettre de plus que doubler la biomasse de poissons indigenes. [Traduit par la Redaction], IntroductionEcological communities are size-structured (Hildrew et al. 2007) whereby large-bodied predators generally consume smaller prey and there are disproportionately more smaller organisms, with a higher total biomass, than large ones [...]

Background: Cryptococcosis is one of the most common life-threatening opportunistic mycoses worldwide. Insidious presentation and slow onset of symptoms make it difficult to recognize, complicating the diagnostic process. Delays in diagnosis may lead to increased mortality. We aim to determine the frequency of missed opportunities for diagnosis of cryptococcosis and its effects on mortality. Methods: To estimate the proportion of individuals with a potentially missed diagnosis for cryptococcosis in hospitalized patients, we conducted a retrospective cohort study using the Healthcare Cost and Utilization Project State Inpatient Databases from 2005 to 2015 from eight states. All hospitalized adult patients diagnosed with cryptococcal infection or cryptococcal meningitis were included. Potentially missed diagnoses were defined as admissions coded for a procedure or diagnosis suggestive of cryptococcosis in the 90-days prior to the initial cryptococcosis admission. Generalized estimating equations models were used to evaluate the association between underlying comorbidities and potential missed diagnosis of cryptococcosis and 90-day all-cause in-hospital mortality. Findings: Of 5,354 patients with cryptococcosis, 2,445 (45·7%) were people living with HIV (PLWH). Among PLWH, 493/2,445 (20·2%) had a potentially missed diagnosis, of which 83/493 (16·8%) died while hospitalized compared with 265/1,952 (13·6%) of those without a potentially missed diagnosis (relative risk [RR] 1·04, 95% CI 0·99–1·09). Among HIV-negative patients, 977/2,909 (33·6%) had a potentially missed diagnosis, of which 236/977 (24·2%) died while hospitalized compared with 298/1,932 (15·4%) of those not missed (RR 1·12, 95% CI 1·07–1·16). Interpretation: Missed opportunities to diagnose cryptococcosis are common despite highly efficacious diagnostic tests and are associated with increased risk of 90-day mortality in HIV-negative patients. A high index of clinical suspicion is paramount to promptly diagnose, treat, and improve cryptococcosis-related mortality. Funding: National Center for Advancing Translational Sciences, Washington University Institute of Clinical and Translational Sciences, and the Agency for Healthcare Research and Quality.

Background In spontaneously hypertensive rats (SHR) we observed profound myocardial metabolic changes during early hypertension before development of cardiac dysfunction and left ventricular hypertrophy. In this study, we evaluated whether metformin improved myocardial metabolic abnormalities and simultaneously prevented contractile dysfunction and left ventricular hypertrophy in SHR. Methods and Results SHR and control Wistar–Kyoto rats were treated with metformin from 2 to 5 months of age, when SHR hearts exhibit metabolic abnormalities and develop cardiac dysfunction and left ventricular hypertrophy. We evaluated the effect of metformin on myocardial glucose uptake rates with dynamic 2‐[18F] fluoro‐2‐deoxy‐D‐glucose positron emission tomography. We used cardiac MRI in vivo to assess the effect of metformin on ejection fraction, left ventricular mass, and end‐diastolic wall thickness, and also analyzed metabolites, AMP‐activated protein kinase and mammalian target‐of‐rapamycin activities, and mean arterial blood pressure. Metformin‐treated SHR had lower mean arterial blood pressure but remained hypertensive. Cardiac glucose uptake rates, left ventricular mass/tibia length, wall thickness, and circulating free fatty acid levels decreased to normal, and ejection fraction improved in treated SHR. Hearts of treated SHR exhibited increased AMP‐activated protein kinase phosphorylation and reduced mammalian target‐of‐rapamycin activity. Cardiac metabolite profiling demonstrated that metformin decreased fatty acyl carnitines and markers of oxidative stress in SHR. Conclusions Metformin reduced blood pressure, normalized myocardial glucose uptake, prevented left ventricular hypertrophy, and improved cardiac function in SHR. Metformin may exert its effects by normalizing myocardial AMPK and mammalian target‐of‐rapamycin activities, improving fatty acid oxidation, and reducing oxidative stress. Thus, metformin may be a new treatment to prevent or ameliorate chronic hypertension–induced left ventricular hypertrophy.

Animals show various behavioural, neural and physiological changes in response to losing aggressive encounters. Here, we investigated affective state, which are emotion-like processes influenced by positive or negative experiences, in a territorial fish following aggressive encounters and explore links to bold/shy behavioural traits. Eighteen 15-month old Murray cod (Maccullochella peelii) received three tests in order to determine bold/shy behavioural traits then underwent a typical go/no-go judgement bias (JB) test. The JB apparatus had five adjacent chambers with access provided by a sliding door and fish underwent a training procedure to enter a chamber at one end of the apparatus to receive a food reward but were chased using a net if they entered the chamber at the opposite end. Only one third (N = 6) of fish successfully completed the training procedure (trained fish), and the remaining 12 fish failed to reach the learning criterion (untrained fish). Trained fish housed with a larger aggressive Murray cod for 24 h were significantly less likely to enter intermediate chambers during probe tests compared to control fish, demonstrating a pessimistic response. Trained fish showed "bolder" responses in emergence and conspecific inspection tests than untrained fish, suggesting that shyer individuals were less able to apply a learned behaviour in a novel environment. Our limited sample was biased towards bold individuals but supports the hypothesis that losing an aggressive encounter leads to pessimistic decision-making.

Humanity's reliance on clean water and the ecosystem services provided makes identifying efficient and effective ways to assess the ecological condition of streams ever more important. We used high throughput sequencing of the 16S rRNA region to explore relationships between stream microbial communities, environmental attributes, and assessments of stream ecological condition. Bacteria and archaea in microbial community samples collected from the water column and from stream sediments during spring and summer were used to replicate standard assessments of ecological condition performed with benthic macroinvertebrate collections via the Benthic Index of Biotic Integrity (BIBI). Microbe-based condition assessments were generated at different levels of taxonomic resolution from phylum to OTU (Operational Taxonomic Units) in order to understand appropriate levels of taxonomic aggregation. Stream sediment microbial communities from both spring and summer were much better than the water column at replicating BIBI condition assessment results. Accuracies were as high as 100% on training data used to build the models and up to 80% on validation data used to assess predictions. Assessments using all OTUs usually had the highest accuracy on training data, but were lower on validation data due to overfitting. In contrast, assessments at the order-level had similar performance accuracy for validation data, and a reduced subset of orders also performed well, suggesting the method could be generalized to other watersheds. Subsets of the important orders responded similarly to environmental gradients compared to the entire community, where strong shifts in community structure occurred for known aquatic stressors such as pH, dissolved organic carbon, and nitrate nitrogen. The results suggest the stream microbes may be useful for assessing the ecological condition of streams and especially useful for stream restorations where many eukaryotic taxa have been eliminated due to prior degradation and are unable to recolonize.

The actin cytoskeleton plays a central role in establishing cell polarity and shape during embryonic morphogenesis. Daam1, a member of the Formin family of actin cytoskeleton regulators, is a Dvl2-binding protein that functions in the Wnt/Planar Cell Polarity (PCP) pathway. To examine the role of the Daam proteins in mammalian development, we generated Daam-deficient mice by gene targeting and found that Daam1, but not Daam2, is necessary for fetal survival. Embryonic development of Daam1 mutants was delayed most likely due to functional defects in the labyrinthine layer of the placenta. Examination of Daam2 and Daam1/2 double mutants revealed that Daam1 and Daam2 are functionally redundant during placental development. Of note, neural tube closure defects (NTD), which are observed in several mammalian PCP mutants, are not observed in Wnt5a or Daam1 single mutants, but arise in Daam1;Wnt5a double mutants. These findings demonstrate a unique function for Daam genes in placental development and are consistent with a role for Daam1 in the Wnt/PCP pathway in mammals.