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International audience; Climate warming is considered to be among the most serious of anthropogenic stresses to the environment, because it not only has direct effects on biodiversity, but it also exacerbates the harmful effects of other human-mediated threats. The associated consequences are potentially severe, particularly in terms of threats to species preservation, as well as in the preservation of an array of ecosystem services provided by biodiversity. Among the most affected groups of animals are insects—central components of many ecosystems—for which climate change has pervasive effects from individuals to communities. In this contribution to the scientists' warning series, we summarize the effect of the gradual global surface temperature increase on insects, in terms of physiology, behavior, phenology, distribution, and species interactions, as well as the effect of increased frequency and duration of extreme events such as hot and cold spells, fires, droughts, and floods on these parameters. We warn that, if no action is taken to better understand and reduce the action of climate change on insects, we will drastically reduce our ability to build a sustainable future based on healthy, functional ecosystems. We discuss perspectives on relevant ways to conserve insects in the face of climate change, and we offer several key recommendations on management approaches that can be adopted, on policies that should be pursued, and on the involvement of the general public in the protection effort.

Salt marshes are vulnerable to climate change-associated sea-level rise and storm-induced surges. Their degradation will likely affect shorebirds relying on this ecosystem. Least Sandpiper (Calidris minutilla) and Pectoral Sandpiper (Calidris melanotos) migrating along coastline habitats typically use salt marshes to rest and replenish their body reserves. Our objective was to test if width of the different vegetation zones within salt marshes affects the occurrence of Least and Pectoral Sandpipers stopping along the St. Lawrence River Estuary, Quebec, Canada, during fall migration. We established 26 survey sites, each 600 m in length, along the shoreline. Shorebird surveys were conducted in 2011 and 2012. We characterized salt marshes by measuring the width of each vegetation zone (lower marsh and upper marsh). We analyzed shorebird presence/not detected data with generalized estimating equations to test the predictions that occurrence of Least Sandpipers and Pectoral Sandpipers increases with width of both the lower and upper marsh. Upper marsh width was positively associated with probability of occurrence in each species. Our results highlight the importance of protecting the integrity of salt marshes for these two species. In the St. Lawrence River Estuary, where landward migration of salt marshes is no longer possible (coastal squeeze), effective management of shorelines is much needed. Otherwise, salt marshes and these two species could be locally jeopardized.

Taurine is a non-proteinogenic sulfonic acid found in high concentrations inside vertebrate cardiomyocytes and its movement across the sarcolemmal membrane is critical for cell volume regulation. Taurine deficiency is rare in mammals, where it impairs cardiac contractility and leads to congestive heart failure. In fish, cardiac taurine levels vary substantially between species and can decrease by up to 60% in response to environmental change but its contribution to cardiac function is understudied. We addressed this gap in knowledge by generating a taurine-deficient rainbow trout (Oncorhynchus mykiss) model using a feed enriched with 3% β-alanine to inhibit cellular taurine uptake. Cardiac taurine was reduced by 17% after 4 weeks with no effect on growth or condition factor. Taurine deficiency did not affect routine or maximum rates of O2 consumption, aerobic scope, or critical swimming speed in whole animals but cardiac contractility was significantly impaired. In isometrically contracting ventricular strip preparations, the force–frequency and extracellular Ca2+-sensitivity relationships were both shifted downward and maximum pacing frequency was significantly lower in β-alanine fed trout. Cardiac taurine deficiency reduces sarcoplasmic reticular Ca2+-ATPase activity in mammals and our results are consistent with such an effect in rainbow trout. Our data indicate that intracellular taurine contributes to the regulation of cardiac contractility in rainbow trout. Aerobic performance was unaffected in β-alanine-fed animals, but further study is needed to determine if more significant natural reductions in taurine may constrain performance under certain environmental conditions.

The heart of tropical fishes is a particularly useful model system in which to investigate mechanisms of hypoxic tolerance. Here we focus on insights gained from two groups of fishes, cichlids and armoured catfishes. Cichlids respond to hypoxia by entering a sustained hypometabolism with decreased heart performance to match whole animal circulatory needs. Heart rate is decreased along with protein turnover to reduce adenosine triphosphate demand. This occurs despite the inherent capacity for high levels of cardiac power development. Although highly hypoxic tolerant at the whole animal level, the heart of cichlids does not have high constitutive activities of glycolytic enzymes compared to other species. Information is conflicting with respect to changes in glycolytic gene expression and enzyme activity following hypoxic exposure with some studies showing increases and others decreases. In contrast to cichlids, species of armoured catfish, that are routinely exposed to water of low oxygen content, do not display hypoxic bradycardia. Under hypoxia there are early changes in glucose trafficking suggestive of activation of glycolysis before lactate accumulation. Thereafter, heart glycogen is mobilized and lactate accumulates in both heart and blood, in some species to very high levels. Heart performance under hypoxia is enhanced by defense of intracellular pH. A functional sarcoplasmic reticulum and binding of hexokinase to the outer mitochondrial membrane may also play a role in cardioprotection. Maintenance of heart performance under hypoxia may relate to a tradeoff between air breathing via a modified stomach and circulatory demands for digestion.

When confined in pairs, juvenile rainbow trout (Oncorhynchus mykiss) form dominance hierarchies in which subordinate fish exhibit characteristic physiological changes including reduced growth rates and chronically elevated plasma cortisol concentrations. We hypothesized that alterations in protein metabolism contribute to the reduced growth rate of socially stressed trout, and predicted that subordinate trout would exhibit reduced rates of protein synthesis coupled with increases in protein degradation. Protein metabolism was assessed in dominant and subordinate fish after 4 days of social interaction, and in fish that were separated after 4 days of interaction for a 4 days recovery period, to determine whether effects on protein metabolism recovered when social stress was alleviated. Protein metabolism was assessed in liver and white muscle by measuring the fractional rate of protein synthesis and markers of protein degradation. In the white muscle of subordinate fish, protein synthesis was inhibited and activities of the ubiquitin-proteasome pathway (UPP) and the autophagy lysosomal system (ALS) were elevated. By contrast, the liver of subordinate fish exhibited increased rates of protein synthesis and activation of the ALS. When allowed to recover from chronic social stress for 4 days, differences in protein metabolism observed in white muscle of subordinate fish during the interaction period disappeared. In liver, protein synthesis returned to baseline levels during recovery from social stress, but markers of protein degradation did not. Collectively, these data support the hypothesis that inhibition of muscle protein synthesis coupled with increases in muscle protein breakdown contribute to the reduced growth rates of subordinate rainbow trout. Supplementary Information The online version contains supplementary material available at 10.1007/s00360-021-01340-6.

Prostate cancer affects thousands of men who undergo clinical screening tests every year. The main biomarker used for the diagnosis of prostate cancer, prostate specific antigen (PSA), presents limitations that justify investigating new biomarkers to improve reliability. Antibodies against the tumor-associated carbohydrate antigen (Tn), or TACA, develop early in carcinogenesis, making them an interesting alternative as a target for prostate cancer diagnostics. In this work, the Tn antigen was synthesized and immobilized on a surface plasmon resonance sensor coated with a polydopamine/polyethylene oxide mixed layer used both as an anchoring surface for Tn capture moieties and to minimize surface fouling. The sensor could be regenerated and reused at least 60 times without any significant loss in sensitivity. Anti-Tn antibodies were detected in the 0-10 nM concentration range with detection limits of 0.1 and 0.3 nM in spiked buffer solutions and diluted human blood serum samples, respectively. Finally, as a proof-of-concept, this carbohydrate-based sensor was used to successfully discriminate blood serum samples from prostate cancer-free and prostate cancer patients.

Bisphenol A (BPA) and its alternative, bisphenol S (BPS), are widespread endocrine disrupting compounds linked in several studies to poor female fertility. Sufficient oocyte competence and subsequent embryo development are highly dependent on oocyte maturation, an intricate process that is vulnerable to BPA. These effects as well as the effects of its analog, BPS, have not been fully elucidated. Although the harmful consequences of bisphenols on the reproductive system are largely due to interferences with canonical gene expression, more recent evidence implicates noncoding RNAs, including microRNAs (miRNA), as significant contributors. The aim of this work was to test the hypothesis that abnormal expression of key miRNAs during oocyte maturation and embryo development occurs following BPA and BPS exposure during maturation. Using qPCR, primary and mature forms of miR-21, -155, -34c, -29a, -10b, -146a were quantified in an in vitro bovine model of matured cumulus-oocyte complexes, fertilized embryos, and cultured cumulus cells after exposure to BPA or BPS at the LOAEL dose (0.05 mg/mL). Expression of miR-21, miR -155, and miR-29a were markedly increased (P = 0.02, 0.04

Assemblages of insect herbivores are structured by plant traits such as nutrient content, secondary metabolites, physical traits, and phenology. Many of these traits are phylogenetically conserved, implying a decrease in trait similarity with increasing phylogenetic distance of the host plant taxa. Thus, a metric of phylogenetic distances and relationships can be considered a proxy for phylogenetically conserved plant traits and used to predict variation in herbivorous insect assemblages among co‐occurring plant species.Using a Holarctic dataset of exposed‐feeding and shelter‐building caterpillars, we aimed at showing how phylogenetic relationships among host plants explain compositional changes and characteristics of herbivore assemblages.Our plant–caterpillar network data derived from plot‐based samplings at three different continents included >28,000 individual caterpillar–plant interactions. We tested whether increasing phylogenetic distance of the host plants leads to a decrease in caterpillar assemblage overlap. We further investigated to what degree phylogenetic isolation of a host tree species within the local community explains abundance, density, richness, and mean specialization of its associated caterpillar assemblage.The overlap of caterpillar assemblages decreased with increasing phylogenetic distance among the host tree species. Phylogenetic isolation of a host plant within the local plant community was correlated with lower richness and mean specialization of the associated caterpillar assemblages. Phylogenetic isolation had no effect on caterpillar abundance or density. The effects of plant phylogeny were consistent across exposed‐feeding and shelter‐building caterpillars.Our study reveals that distance metrics obtained from host plant phylogeny are useful predictors to explain compositional turnover among hosts and host‐specific variations in richness and mean specialization of associated insect herbivore assemblages in temperate broadleaf forests. As phylogenetic information of plant communities is becoming increasingly available, further large‐scale studies are needed to investigate to what degree plant phylogeny structures herbivore assemblages in other biomes and ecosystems., Host plant phylogenetic relationships have been shown to affect community composition and interaction networks of associated insect herbivores. Using a cross‐continental dataset, we showed that phylogenetically isolated hosts harbored less diverse and less specialized caterpillar assemblages. Our results suggest that a combination of phylogenetic information and compositional structure of the host plant community provides useful measures to predict the structure of herbivore assemblages among coexisting plant species.

CD8+ T cell–mediated immunity is critical for host defense against viruses and requires mitochondria-mediated type I IFN (IFN-I) signaling for optimal protection. Cyclophilin D (CypD) is a mitochondrial matrix protein that modulates the mitochondrial permeability transition pore, but its role in IFN-I signaling and CD8+ T cell responses to viral infection has not been previously explored. In this study, we demonstrate that CypD plays a critical extrinsic role in the survival of Ag-specific CD8+ T cell following acute viral infection with lymphocytic choriomeningitis virus in mice. CypD deficiency resulted in reduced IFN-I and increased CD8+ T cell death, resulting in a reduced antiviral CD8+ T cell response. In addition, CypD deficiency was associated with an increase in pathogen burden at an early time-point following infection. Furthermore, our data demonstrate that transfer of wild-type macrophages (expressing CypD) to CypD-deficient mice can partially restore CD8+ T cell responses. These results establish that CypD plays an extrinsic role in regulating optimal effector CD8+ T cell responses to viral infection. Furthermore, this suggests that, under certain circumstances, inhibition of CypD function may have a detrimental impact on the host’s ability to respond to viral infection.

SummaryRenewable energy helps meet the growing energetic demand while reducing greenhouse gas emissions. Despite its environmental benefits, production of wind energy can adversely affect wildlife populations, including birds. In some species, indirect impacts such as habitat loss and disturbance may be more important than fatalities caused by collisions with turbines. Bicknell’s Thrush Catharus bicknelli, one of the most endangered bird species in North America, may be threatened by wind energy production because it breeds at high elevation sites, which are often prized for their wind potential. Our study had two objectives: we first aimed to document the impacts of the construction and operation of a wind energy facility without mitigation strategy on the occurrence of the Bicknell’s Thrush. At a second facility, we then tested the effectiveness of turbine micro-siting as an effective mitigation strategy to reduce the impacts of wind-energy development on the species. We conducted avian point-counts at 143 locations spread across both facilities in Quebec (Canada) at different periods: before, during and after construction. We modelled the probability of occurrence of the species at point-counts as a function of period, forest loss caused by wind energy development, distance to the nearest turbine and habitat suitability. At the facility without mitigation, we found that the probability of occurrence decreased during construction and early operation at high elevation sites, where most of the turbines were erected. However, the Bicknell’s Thrush recolonized high elevation sites eight years post-construction. In addition, we did not detect a significant impact of wind energy production on the species’ occurrence at the facility where micro-siting was applied. We conclude that habitat loss and disturbance during construction are the main impacts of wind energy production on the Bicknell’s Thrush and that micro-siting appears to be a promising mitigation strategy.

Vertical niche partitioning might be one of the main driving forces explaining the high diversity of forest ecosystems. However, the forest's vertical dimension has received limited investigation, especially in temperate forests. Thus, our knowledge about how communities are vertically structured remains limited for temperate forest ecosystems. In this study, we investigated the vertical structuring of an arboreal caterpillar community in a temperate deciduous forest of eastern North America. Within a 0.2-ha forest stand, all deciduous trees ≥ 5 cm diameter at breast height (DBH) were felled and systematically searched for caterpillars. Sampled caterpillars were assigned to a specific stratum (i.e. understory, midstory, or canopy) depending on their vertical position and classified into feeding guild as either exposed feeders or shelter builders (i.e. leaf rollers, leaf tiers, webbers). In total, 3892 caterpillars representing 215 species of butterflies and moths were collected and identified. While stratum had no effect on caterpillar density, feeding guild composition changed significantly with shelter-building caterpillars becoming the dominant guild in the canopy. Species richness and diversity were found to be highest in the understory and midstory and declined strongly in the canopy. Family and species composition changed significantly among the strata; understory and canopy showed the lowest similarity. Food web analyses further revealed an increasing network specialization towards the canopy, caused by an increase in specialization of the caterpillar community. In summary, our study revealed a pronounced stratification of a temperate forest caterpillar community, unveiling a distinctly different assemblage of caterpillars dwelling in the canopy stratum.

The epidermal growth factor receptor (EGFR), when carrying an activating mutation like del19 or L858R, acts as an oncogenic driver in a subset of lung tumors. While tumor responses to tyrosine kinase inhibitors (TKIs) are accompanied by marked tumor shrinkage, the response is usually not durable. Most patients relapse within two years of therapy often due to acquisition of an additional mutation in EGFR kinase domain that confers resistance to TKIs. Crucially, oncogenic EGFR harboring both resistance mutations, T790M and C797S, can no longer be inhibited by currently approved EGFR TKIs. Here, we describe the discovery of BI-4020, which is a noncovalent, wild-type EGFR sparing, macrocyclic TKI. BI-4020 potently inhibits the above-described EGFR variants and induces tumor regressions in a cross-resistant EGFRdel19 T790M C797S xenograft model. Key was the identification of a highly selective but moderately potent benzimidazole followed by complete rigidification of the molecule through macrocyclization.

String-pulling is among the most widespread cognitive tasks used to test problem-solving skills in mammals and birds. The task requires animals to comprehend that pulling on a non-valuable string moves an otherwise inaccessible food reward to within their reach. Although at least 90 avian species have been administered the string-pull test, all but five of them were perching birds (passeriformes) or parrots (psittaciformes). Waterbirds (Aequorlitornithes) are poorly represented in the cognitive literature, yet are known to engage in complex foraging behaviours. In this study, we tested whether free-living ring-billed gulls (Larus delawarensis), a species known for their behavioural flexibility and foraging innovativeness, could solve a horizontal string-pull test. Here, we show that 25% (26/104) of the ring-billed gulls that attempted to solve the test at least once over a maximum of three trials were successful, and that 21% of them (22/104) succeeded during their first attempt. Ring-billed gulls are thus the first waterbird known to solve a horizontal single-string-rewarded string-pull test. Since innovation rate and problem-solving are associated with species' ability to endure environmental alterations, we suggest that testing the problem-solving skills of other species facing environmental challenges will inform us of their vulnerability in a rapidly changing world.

Fossorial locomotion is often considered as the most energetically costly of all terrestrial locomotion. Small arctic rodents, such as lemmings, dig tunnels not only in the soil but also through the snowpack, which is present for over 8 months of the year. Lemmings typically dig in the softest snow layer called the depth hoar but with climate change, melt‐freeze and rain‐on‐snow (ROS) events are expected to increase in the Arctic, leading to a higher frequency of hardened snowpacks. We assessed the impacts of snow hardness on the locomotion of two lemming species showing different morphological adaptations for digging. We hypothesized that an increase in snow hardness would (1) decrease lemming performance and (2) increase their effort while digging, but those responses would differ between lemming species. We exposed four brown lemmings (Lemmus trimucronatus) and three collared lemmings (Dicrostonyx groenlandicus) to snow of different hardness (soft, hard, and ROS) during 30‐min trials (n = 63 trials) in a cold room and filmed their behavior. We found that the digging speed and tunnel length of both species decreased with snow hardness and density, underlining the critical role of snow properties in affecting lemming digging performance. During the ROS trials, time spent digging by lemmings increased considerably and they also started using their incisors to help break the hard snow, validating our second hypothesis. Overall, digging performance was higher in collared lemmings, the species showing more morphological adaptations to digging, than in brown lemmings. We conclude that the digging performance of lemming is highly dependent on snowpack hardness and that the anticipated increase in ROS events may pose a critical energetic challenge for arctic rodent populations.

Long-distance migrants are under strong selection to arrive on their breeding grounds at a time that maximizes fitness. Many arctic birds start nesting shortly after snow recedes from their breeding sites and timing of snowmelt can vary substantially over the breeding range of widespread species. We tested the hypothesis that migration schedules of individuals co-occurring at the same non-breeding areas are adapted to average local environmental conditions encountered at their specific and distant Arctic breeding locations. We predicted that timing of breeding site availability (measured here as the average snow-free date) should explain individual variation in departure time from shared non-breeding areas. We tested our prediction by tracking American Golden-Plovers (Pluvialis dominica) nesting across the North-American Arctic. These plovers use a non-breeding (wintering) area in South America and share a spring stopover area in the nearctic temperate grasslands, located >1,800 km away from their nesting locations. As plovers co-occur at the same non-breeding areas but use breeding sites segregated by latitude and longitude, we could disentangle the potential confounding effects of migration distance and timing of breeding site availability on individual migration schedule. As predicted, departure date of individuals stopping-over in sympatry was positively related to the average snow-free date at their respective breeding location, which was also related to individual onset of incubation. Departure date from the shared stopover area was not explained by the distance between the stopover and the breeding location, nor by the stopover duration of individuals. This strongly suggests that plover migration schedule is adapted to and driven by the timing of breeding site availability per se. The proximate mechanism underlying the variable migration schedule of individuals is unknown and may result from genetic differences or individual learning. Temperatures are currently changing at different speeds across the Arctic and this likely generates substantial heterogeneity in the strength of selection pressure on migratory schedule of arctic birds migrating sympatrically.

Current therapeutic interventions to eradicate latent HIV (“reservoir”) and restore immune function in ART-treated HIV infection have yet to show efficacy. To explore mechanisms of HIV persistence, we apply an integrated systems biology approach and identify a distinct group of individuals with poor CD4 T-cell reconstitution (Immunologic non-responders, “INRs”) and high frequencies of cells with inducible HIV. Contrary to the prevailing notion that immune activation drives HIV persistence and immune dysfunction, peripheral blood leukocytes from these subjects have enhanced expression of a network of genes regulated by cellular senescence. In these subjects, increased frequencies of regulatory T cells and expression of the TGF-β signaling cascade are concomitant with the downregulation of cell cycle and metabolism in CD4 central memory T (TCM) cells. These cascades, downstream of TGF-β, lead to the accumulation of PD-1 expressing CD4 TCM and are associated with an increase in frequencies of cells with inducible HIV ex vivo. In vitro validation confirmed that this cellular profile was driven by a β-hydroxybutyrates/bile acid rich metabolic milieu and resulted in TGF-β associated latency establishment. Our findings identify targets for PD-1 or TGF-β specific interventions that can overcome cellular senescence; these therapeutic approaches have shown safety and efficacy in cancer, and may prove to be crucial for HIV eradication.

In the tropics, antagonistic seed predation networks may have different properties than mutualistic pollination and seed dispersal networks, but the former have been considerably less studied. We tested whether the structure of antagonistic tripartite networks composed of host plants, insects developing within seeds and fruits, and their insect parasitoids could be predicted from plant phylogenetic distance and plant traits. We considered subsets of the networks (“subnetworks”) at three rainforest locations (Panama, Thailand, Papua New Guinea), based on insect families, plant families or plant functional groups. We recorded 3,197 interactions and observed a low percentage of realized interactions, especially in Panama, where insect host specificity was higher than in Thailand or New Guinea. Several factors may explain this, including insect faunal composition, incidence of dry fruits, high fruit production and high occurrence of Fabaceae at the Panamanian site. Host specificity was greater among seed-eaters than pulp-eaters and for insects feeding on dry fruits as opposed to insects feeding on fleshy fruits. Plant species richness within plant families did not influence insect host specificity, but site characteristics may be important in this regard. Most subnetworks were extremely specialized, such as those including Tortricidae and Bruchinae in Panama. Plant phylogenetic distance, plant basal area and plant traits (fruit length, number of seeds per fruit) had important effects on several network statistics in regressions weighted by sampling effort. A path analysis revealed a weak direct influence of plant phylogenetic distance on parasitoid richness, indicating limited support for the “nasty host hypothesis”. Our study emphasizes the duality between seed dispersal and seed predation networks in the tropics, as key plant species differ and host specificity tends to be low in the former and higher in the latter. This underlines the need to study both types of networks for sound practices of forest regeneration and conservation.

Cystic ovarian disease (COD) is a major contributor to infertility in cattle, with 30% of cows developing ovarian cysts during a given lactation and becoming anovulatory. The cause of COD has remained elusive and is thought to be multifactorial, with angiogenic and genetic contributions proposed. There is an increasing body of work suggesting that microRNAs (miRNAs) may be involved in a number of ovarian-based reproductive disorders. Changes in miRNA expression can affect a multitude of genes and may be important regulators of the dynamic processes involved in each ovarian cycle. We hypothesized that miRNAs are integral to the regulation of critical ovarian processes such as angiogenesis and follicular development and that altered miRNA expression contributes to the onset and progression of ovarian dysfunction and reproductive disorders. Eight miRNAs (miR-15a, -18a, -20a, 21, -29a, -126, -132, Let7a) known to target vascular endothelial growth factor (VEGF), thrombospondin-1 (TSP-1), and play a role in both angiogenesis and folliculogenesis, were selected for analysis. miRNA, mRNA, and protein expression were analyzed in large and cystic bovine follicles using qPCR, western blot, and immunohistochemistry. miR-29a was found to be upregulated in cystic follicles, whereas miR-132 expression was downregulated. VEGF expression increased in cystic follicles at both the transcript and protein level, while no significant differences in TSP-1 expression was observed. Our findings suggest that miR-29a and miR-132 may play an important role in maintaining the balance between VEGF and TSP-1 expression in the ovary, and if disrupted, could potentiate ovarian-based reproductive disorders such as PCOS and cystic ovarian disorder.

Common scab of potato causes important economic losses worldwide following the development of necrotic lesions on tubers. In this study, the genomes of 14 prevalent scab-causing Streptomyces spp. isolated from Prince Edward Island, one of the most important Canadian potato production areas, were sequenced and annotated. Their phylogenomic affiliation was determined, their pan-genome was characterized, and pathogenic determinants involved in their virulence, ranging from weak to aggressive, were compared. 13 out of 14 strains clustered with Streptomyces scabiei, while the last strain clustered with Streptomyces acidiscabies. The toxicogenic and colonization genomic regions were compared, and while some atypical gene organizations were observed, no clear correlation with virulence was observed. The production of the phytotoxin thaxtomin A was also quantified and again, contrary to previous reports in the literature, no clear correlation was found between the amount of thaxtomin A secreted, and the virulence observed. Although no significant differences were observed when comparing the presence/absence of the main virulence factors among the strains of S. scabiei, a distinct profile was observed for S. acidiscabies. Several mutations predicted to affect the functionality of some virulence factors were identified, including one in the bldA gene that correlates with the absence of thaxtomin A production despite the presence of the corresponding biosynthetic gene cluster in S. scabiei LBUM 1485. These novel findings obtained using a large number of scab-causing Streptomyces strains are challenging some assumptions made so far on Streptomyces’ virulence and suggest that other factors, yet to be characterized, are also key contributors.

We report on the development of surface plasmon resonance (SPR) sensors and matching ELISAs for the detection of nucleocapsid and spike antibodies specific against the novel coronavirus 2019 (SARS-CoV-2) in human serum, plasma and dried blood spots (DBS). When exposed to SARS-CoV-2 or a vaccine against SARS-CoV-2, the immune system responds by expressing antibodies at levels that can be detected and monitored to identify the fraction of the population potentially immunized against SARS-CoV-2 and support efforts to deploy a vaccine strategically. A SPR sensor coated with a peptide monolayer and functionalized with various sources of SARS-CoV-2 recombinant proteins expressed in different cell lines detected human anti-SARS-CoV-2 IgG antibodies in clinical samples. Nucleocapsid expressed in different cell lines did not significantly change the sensitivity of the assays, whereas the use of a CHO cell line to express spike ectodomain led to excellent performance. This bioassay was performed on a portable SPR instrument capable of measuring 4 biological samples within 30 minutes of sample/sensor contact and the chip could be regenerated at least 9 times. Multi-site validation was then performed with in-house and commercial ELISA, which revealed excellent cross-correlations with Pearson's coefficients exceeding 0.85 in all cases, for measurements in DBS and plasma. This strategy paves the way to point-of-care and rapid testing for antibodies in the context of viral infection and vaccine efficacy monitoring.

Objective Little is known about self-medication with cannabis post-recreational cannabis legalization in Canada. We aimed to establish a detailed portrait of self-medication with cannabis among adults in Quebec. Methods We conducted an online survey from November 2020 to January 2021 among individuals aged ≥ 21 years, who endorsed using cannabis bought in legal recreational cannabis stores to self-medicate a health condition. Data were analysed using descriptive statistics and stratified according to sex, age and the type of cannabis use (exclusively medical versus medical and recreational use). Results 489 participants were included. Median age was 34 years, and 48% were women. About 25% reported an exclusive medical use of cannabis. Treated conditions included anxiety (70%), insomnia (56%), pain (53%), depression (37%), and many other. Reasons for not consulting in cannabis clinics included lack of information (52%), complexity of the process (39%), accessibility of cannabis clinics (23%) and other.

Molecules present in an animal's environment can indicate the presence of predators, food, or sexual partners and consequently, induce migratory, reproductive, foraging, or escape behaviors. Three sensory systems, the olfactory, gustatory, and solitary chemosensory cell (SCC) systems detect chemical stimuli in vertebrates. While a great deal of research has focused on the olfactory and gustatory system over the years, it is only recently that significant attention has been devoted to the SCC system. The SCCs are microvillous cells that were first discovered on the skin of fish, and later in amphibians, reptiles, and mammals. Lampreys also possess SCCs that are particularly numerous on cutaneous papillae. However, little is known regarding their precise distribution, innervation, and function. Here, we show that sea lampreys (Petromyzon marinus L.) have cutaneous papillae located around the oral disk, nostril, gill pores, and on the dorsal fins and that SCCs are particularly numerous on these papillae. Tract-tracing experiments demonstrated that the oral and nasal papillae are innervated by the trigeminal nerve, the gill pore papillae are innervated by branchial nerves, and the dorsal fin papillae are innervated by spinal nerves. We also characterized the response profile of gill pore papillae to some chemicals and showed that trout-derived chemicals, amino acids, and a bile acid produced potent responses. Together with a companion study (Suntres et al., Journal of Comparative Neurology, this issue), our results provide new insights on the function and evolution of the SCC system in vertebrates.

Coleoid cephalopods, including the European cuttlefish (Sepia officinalis), possess the remarkable ability to fully regenerate an amputated arm with no apparent fibrosis or loss of function. In model organisms, regeneration usually occurs as the induction of proliferation in differentiated cells. In rare circumstances, regeneration can be the product of naive progenitor cells proliferating and differentiating de novo. In any instance, the immune system is an important factor in the induction of the regenerative response. Although the wound response is well-characterized, little is known about the physiological pathways utilized by cuttlefish to reconstruct a lost arm. In this study, the regenerating arms of juvenile cuttlefish, with or without exposure at the time of injury to sterile bacterial lipopolysaccharide extract to provoke an antipathogenic immune response, were assessed for the transcription of early tissue lineage developmental genes, as well as histological and protein turnover analyses of the resulting regenerative process. The transient upregulation of tissue-specific developmental genes and histological characterization indicated that coleoid arm regeneration is a stepwise process with staged specification of tissues formed de novo, with immune activation potentially affecting the timing but not the result of this process. Together, the data suggest that rather than inducing proliferation of mature cells, developmental pathways are reinstated, and that a pool of naive progenitors at the blastema site forms the basis for this regeneration. Programa Mar2020 [16-02-01-FMP-53] Fundacao para a Ciencia e a TecnologiaPortuguese Foundation for Science and Technology [IF/00576/2014] Natural Sciences and Engineering Research Council of CanadaNatural Sciences and Engineering Research Council of Canada [RGPIN 2018-05160, RGPIN-2018-03884] Vanier Canada Graduate Scholarship

BackgroundAdequate cellular thymidylate (dTMP) pools are essential for preservation of nuclear and mitochondrial genome stability. Previous studies have indicated that disruption in dTMP synthesis in the nucleus leads to increased uracil misincorporation into DNA affecting genome stability. To date, the effects of impaired mitochondrial dTMP synthesis in non- transformed tissues have been understudied.ObjectiveThis study aimed to determine the effects of decreased serine hydroxymethyltransferase 2 (Shmt2) expression and dietary folate deficiency on mitochondrial DNA integrity and mitochondrial function in mouse tissues.MethodsLiver mitochondrial DNA (mtDNA) content, and uracil content in liver mtDNA was measured in Shmt2+/- and Shmt2+/+ mice weaned onto either a folate-sufficient control diet (2 mg/kg folic acid, C) or a modified diet lacking folic acid (0 mg/kg folic acid, FD) for 7 wks. Shmt2+/- and Shmt2+/+ mouse embryonic fibroblasts (MEF cells) were cultured in defined culture medium containing either 0 or 25 nM folate to assess proliferative capacity and mitochondrial function.ResultsShmt2+/- mice exhibited 48-67% reduction in SHMT2 protein levels in tissues. Interestingly, Shmt2+/- mice consuming the folate-sufficient C diet exhibited a 25% reduction in total folate in liver mitochondria. There was also a >20-fold increase in uracil in liver mtDNA in Shmt2+/- mice consuming the C diet, and dietary folate deficiency also increased uracil content in mouse liver mtDNA from both Shmt2+/+ and Shmt2+/- mice. Furthermore, decreased Shmt2 expression in MEF cells reduced cell proliferation, mitochondrial membrane potential, and oxygen consumption rate.ConclusionsThis study demonstrates that Shmt2 heterozygosity and dietary folate deficiency impair mitochondrial dTMP synthesis, as evidenced by the increased uracil in mtDNA. In addition, Shmt2 heterozygosity impairs mitochondrial function in MEF cells. These findings suggest that elevated uracil in mtDNA may impair mitochondrial function.

Type-I interferon (IFN-I) signals exert a critical role in disease progression during viral infections. However, the immunomodulatory mechanisms by which IFN-I dictates disease outcomes remain to be fully defined. Here we report that IFN-I signals mediate thymic atrophy in viral infections, with more severe and prolonged loss of thymic output and unique kinetics and subtypes of IFN-α/β expression in chronic infection compared to acute infection. Loss of thymic output was linked to inhibition of early stages of thymopoiesis (DN1-DN2 transition, and DN3 proliferation) and pronounced apoptosis during the late DP stage. Notably, infection-associated thymic defects were largely abrogated upon ablation of IFNαβR and partially mitigated in the absence of CD8 T cells, thus implicating direct as well as indirect effects of IFN-I on thymocytes. These findings provide mechanistic underpinnings for immunotherapeutic strategies targeting IFN-1 signals to manipulate disease outcomes during chronic infections and cancers.

We report 2 cases of severe coronavirus disease 2019 requiring prolonged hospitalization complicated by the late onset of opportunistic fungal infections, histoplasmosis, and cryptococcosis.

Therapeutic interventions to eradicate latent HIV in ART-treated infection have yet to show efficacy. We used a systems biology approach to identify a subset of ART-treated individuals with immune-dysfunction that had the highest frequencies of cells with inducible HIV. Contrary to the prevailing notion that immune activation drives HIV persistence, blood from these individuals was enriched in senescence-inducing genes (high FOXO3, SMAD2 and IRF3), Treg frequencies and TGF-β signaling expression. In these "Senescent-INRs", high Firmicute phylum plasma nucleotides and butyrate/bile acids (like a-ketobutyrate) correlated with Treg frequencies and inducible HIV levels. Stimulation of naive CD4 T-cells with a-ketobutyrate led to TGF-β producing Treg differentiation, and PD-1 up-regulation on less differentiated cells. A dose dependent increase in latent HIV-infected memory CD4 T-cells was observed after TGF-β stimulation. Senescence cascades identified here can be targeted by PD-1/TGF-β specific interventions that have shown safety/efficacy in cancer, and can be crucial for HIV eradication.

Robust data to refute or support claims of global insect decline are currently lacking, particularly for the soil fauna in the tropics. DNA metabarcoding represents a powerful approach for rigorous spatial and temporal monitoring of the taxonomically challenging soil fauna. Here, we provide a detailed field protocol, which was successfully applied in Barro Colorado Island (BCI) in Panama, to collect soil samples and arthropods in a tropical rainforest, to be later processed with metabarcoding. We also estimate the proportion of soil/litter ant, springtail and termite species from the local fauna that can be detected by metabarcoding samples obtained either from Berlese-Tullgren (soil samples), Malaise or light traps. Each collecting method detected a rather distinct fauna. Soil and Malaise trap samples detected 213 species (73%) of all target species. Malaise trap samples detected many ant species, whereas soil samples were more efficient at detecting springtail and termite species. With respect to long-term monitoring of soil-dwelling and common species (more amenable to statistical trends), the best combination of two methods were soil and light trap samples, detecting 94% of the total of common species. A protocol including 100 soil, 40 Malaise and 80 light trap samples annually processed by metabarcoding would allow the long-term monitoring of at least 11%, 18% and 16% of species of soil/litter ants, springtails and termites, respectively, present on BCI, and a high proportion of the total abundance (up to 80% of all individuals) represented by these taxa.

The southern extent of the boreal forest in North America has experienced intensive human disturbance in the past decades. Among these, forest harvesting leads to the substantial loss of late-successional stands that include key habitat attributes for several avian species. The American Three-toed Woodpecker, Picoides dorsalis, is associated with continuous old spruce forests in the eastern part of its range. In this study, we assess the influence of habitat characteristics at different scales on the occupancy of American Three-toed Woodpecker in a heavily managed boreal landscape of northeastern Canada, and we inferred species occupancy at the regional scale. We conducted 185 playback stations over two breeding seasons and modelled the occupancy of the species while taking into account the probability of detection. American Three-toed Woodpecker occupancy was lower in stands with large areas recently clear-cut, and higher in landscapes with large extents of old-growth forest dominated by black spruce. At the regional scale, areas with high probability of occupancy were scarce and mostly within protected areas. Habitat requirements of the American Three-toed Woodpecker during the breeding season, coupled with over-all low occupancy rate in our study area, challenge its long-term sustainability in such heavily managed landscapes. Additionally, the scarcity of areas of high probability of occupancy in the region suggest that the ecological role of old forest outside protected areas could be compromised.

SummaryCurrent therapeutic interventions to eradicate latent HIV (“reservoir”) and restore immune function in ART-treated HIV infection have yet to show efficacy. To explore mechanisms of HIV persistence, we apply an integrated systems biology approach and identify a distinct group of individuals with poor CD4 T-cell reconstitution (Immunologic non-responders, “INRs”) and high frequencies of cells with inducible HIV. Contrary to the prevailing notion that immune activation drives HIV persistence and immune dysfunction, peripheral blood leukocytes from these subjects have enhanced expression of a network of genes regulated by cellular senescence driving transcription factors (TFs) FOXO3, SMAD2 and IRF3. In these subjects, increased frequencies of regulatory T cells and expression of the TGF-β signaling cascade are complimented by the downregulation of cell cycle, metabolic and pro-inflammatory pathways. Lactobacillaceae family and metabolites (members of the butyrate family – i.e. α-ketobutyrate) were correlated with Treg frequencies in “Senescent-INRs”ex vivo,triggered the differentiation of TGF-β producing Tregs and promoted HIV latency establishmentin vitro.These cascades, downstream of PD-1/TGF-β, prevent memory T cell differentiation and are associated with an increase in frequencies of cells with inducible HIVex vivo.Our findings identify cellular senescence responses that can be targeted by PD-1 or TGF-β specific interventions that have shown safety and efficacy in cancer, and may prove to be crucial for HIV eradication.

Background Ectopic expression of a defined set of transcription factors allows the reprogramming of mammalian somatic cells to pluripotency. Despite continuous progress in primate and rodent reprogramming, limited attention has been paid to cell reprogramming in domestic and companion species. Previous studies attempting to reprogram canine cells have mostly assessed a small number of presumptive canine induced pluripotent stem cell (iPSC) lines for generic pluripotency attributes. However, why canine cell reprogramming remains extremely inefficient is poorly understood. Methods To better characterize the initial steps of pluripotency induction in canine somatic cells, we optimized an experimental system where canine fetal fibroblasts (cFFs) are transduced with the Yamanaka reprogramming factors by Sendai virus vectors. We use quantitative PCR arrays to measure the expression of 80 target genes at various stages of canine cell reprogramming. We ask how cFF reprogramming is influenced by small molecules affecting the epigenomic modification 5-hydroxymethylcytosine, specifically L-ascorbic acid and retinoic acid (AA/RA). Results We found that the expression and catalytic output of a class of 2-oxoglutarate-dependent (2-OG) hydroxylases, known as ten-eleven translocation (TET) enzymes, can be modulated in canine cells treated with AA/RA. We further show that AA/RA treatment induces TET1 expression and facilitates early canine reprogramming, evidenced by upregulation of epithelial and pluripotency markers. Using a chemical inhibitor of 2-OG hydroxylases, we demonstrate that 2-OG hydroxylase activity regulates the expression of a subset of genes involved in mesenchymal-to-epithelial transition (MET) and pluripotency in early canine reprogramming. We identify a set of transcription factors depleted in maturing reprogramming intermediates compared to pluripotent canine embryonic stem cells. Conclusions Our findings highlight 2-OG hydroxylases have evolutionarily conserved and divergent functions regulating the early reprogramming of canine somatic cells and show reprogramming conditions can be rationally optimized for the generation of maturing canine iPSC.

The capacity of ectotherms to adapt to new thermal habitat depends on the physiological impact of changes in temperature. We observed here that heart tolerance to oxidative stress, dictated by membrane fatty acid profile, might be a significant driver in setting upper thermal limits in Arctic charr., The cardiovascular system is a major limiting system in thermal adaptation, but the exact physiological mechanisms underlying responses to thermal stress are still not completely understood. Recent studies have uncovered the possible role of reactive oxygen species production rates of heart mitochondria in determining species’ upper thermal limits. The present study examines the relationship between individual response to a thermal challenge test (CTmax), susceptibility to peroxidation of membrane lipids, heart fatty acid profiles and cardiac antioxidant enzyme activities in two salmonid species from different thermal habitats (Salvelinus alpinus, Salvelinus fontinalis) and their hybrids. The susceptibility to peroxidation of membranes in the heart was negatively correlated with individual thermal tolerance. The same relationship was found for arachidonic and eicosapentaenoic acid. Total H2O2 buffering activity of the heart muscle was higher for the group with high thermal resistance. These findings underline a potential general causative relationship between sensitivity to oxidative stress, specific fatty acids, antioxidant activity in the cardiac muscle and thermal tolerance in fish and likely other ectotherms. Heart fatty acid profile could be indicative of species resilience to global change, and more importantly the plasticity of this trait could predict the adaptability of fish species or populations to changes in environmental temperature.

The development of new, low-cost vaccines and effective gene therapies requires accurate delivery and high-level expression of candidate genes. We developed a plasmid vector, pIDV-II, that allows for both easy manipulation and high expression of exogenous genes in mammalian cells. This plasmid is based upon the pVax1 plasmid and shares a common structure with typical mammalian transcription units. It is composed of a chicken β-actin promoter (CAG), followed by an intron and flanked by two restriction sites, and also includes a post-transcriptional regulatory element, followed by a transcriptional termination signal. While the modification of pVax1 elements either decreased eGFP expression levels or had no effect at all, replacement of the promoter, the poly-A signal, deletion of the T7 and AmpR promoters, and inversion of the ORI-Neo/Kan cassette, significantly increased in vitro eGFP expression with the modified plasmid called pIDV-II. To further evaluate our vector, expression levels of three viral antigens were compared in cell lines transfected either with pVax1 or pCAGGS backbones as controls. Higher transgene expression was consistently observed with pIDV-II. The humoral and cellular responses generated in mice immunized with pIDV-II vs pVax1 expressing each viral antigen individually were superior by 2-fold or more as measured by ELISA and ELISPOT assays. Overall these results indicate that pIDV-II induces robust transgene expression, with concomitant improved cellular and humoral immune responses against the transgene of interest over pVax1. The new vector, pIDV-II, offers an additional alternative for DNA based vaccination and gene therapy for animal and human use.

Consuming omega-3 fatty acids (n-3 LCPUFAs) during development improves cognition in mammals, but the effect remains untested in other taxa. In aquatic ecosystems, n-3 LCPUFAs are produced by phytoplankton and bioaccumulate in the food web. Alarmingly, the warming and acidification of aquatic systems caused by climate change impair n-3 LCPUFA production, with an anticipated decrease of 80% by the year 2100. We tested whether n-3 LCPUFA consumption affects the physiology, morphology, behaviour and cognition of the chicks of a top marine predator, the ring-billed gull. Using a colony with little access to n-3 LCPUFAs, we supplemented siblings from 22 fenced nests with contrasting treatments from hatching until fledging; one sibling received n-3 LCPUFA-rich fish oil and the other, a control sucrose solution without n-3 LCPUFAs. Halfway through the nestling period, half the chicks receiving fish oil were switched to the sucrose solution to test whether n-3 LCPUFA intake remains crucial past the main growth phase (chronic versus transient treatments). Upon fledging, n-3 LCPUFAs were elevated in the blood and brains of chicks receiving the chronic treatment, but were comparable to control levels among those receiving the transient treatment. Across the entire sample, chicks with elevated n-3 LCPUFAs in their tissues fledged earlier despite their morphology and activity levels being unrelated to fledging age. Fledging required chicks to escape fences encircling their nest. We therefore interpret fledging age as a possible indicator of cognition, with chicks with improved cognition fledging earlier. These results provide insight into whether declining dietary n-3 LCPUFAs will compromise top predators' problem-solving skills, and thus their ability to survive in a rapidly changing world., Summary: Supplementing gull chicks with omega-3 fatty acids in the context of natural deficiency improves their cognitive development, as shown by their ability to fledge earlier by escaping a fence encircling their nest.

Flaviviridae infections represent a major global health burden. By deciphering mechanistic aspects of hepatitis C virus (HCV)-host interactions, one could discover common strategy for inhibiting the replication of related flaviviruses. By elucidating the HCV interactome, we identified the 17-beta-hydroxysteroid dehydrogenase type 12 (HSD17B12) as a human hub of the very-long-chain fatty acid (VLCFA) synthesis pathway and core interactor. Here we show that HSD17B12 knockdown (KD) impairs HCV replication and reduces virion production. Mechanistically, depletion of HSD17B12 induces alterations in VLCFA-containing lipid species and a drastic reduction of lipid droplets (LDs) that play a critical role in virus assembly. Oleic acid supplementation rescues viral RNA replication and production of infectious particles in HSD17B12 depleted cells, supporting a specific role of VLCFA in HCV life cycle. Furthermore, the small-molecule HSD17B12 inhibitor, INH-12, significantly reduces replication and infectious particle production of HCV as well as dengue virus and Zika virus revealing a conserved requirement across Flaviviridae virus family. Overall, the data provide a strong rationale for the advanced evaluation of HSD17B12 inhibition as a promising broad-spectrum antiviral strategy for the treatment of Flaviviridae infections.

We report 2 cases of infective endocarditis in injection drug users due to Brucella infection. Although cardiac involvement is a frequent sequela of brucellosis and endocarditis is often seen with injection drug use, Brucella endocarditis in persons who inject drugs without zoonotic exposure has not been reported to date.

Eating disorders (EDs) are increasingly frequent. Their pathophysiology involves disturbance of peptide signaling and the microbiota&ndash, gut&ndash, brain axis. This study analyzed peptides and corresponding immunoglobulin (Ig) concentrations in groups of ED. In 120 patients with restrictive (R), bulimic (B), and compulsive (C) ED, the plasma concentrations of leptin, glucagon-like peptide-1 (GLP-1), peptide YY (PYY), and insulin were analyzed by Milliplex and those of acyl ghrelin (AG), des-acyl ghrelin (DAG), and &alpha, melanocyte-stimulating hormone (&alpha, MSH) by ELISA kits. Immunoglobulin G (in response to an antigen) concentrations were analyzed by ELISA, and their affinity for the respective peptide was measured by surface plasmon resonance. The concentrations of leptin, insulin, GLP-1, and PYY were higher in C patients than in R patients. On the contrary, &alpha, MSH, DAG, and AG concentrations were higher in R than in C patients. After adjustment for body mass index (BMI), differences among peptide concentrations were no longer different. No difference in the concentrations of the IgG was found, but the IgG concentrations were correlated with each other. Although differences of peptide concentrations exist among ED subtypes, they may be due to differences in BMI. Changes in the concentration and/or affinity of several anti-peptide IgG may contribute to the physiopathology of ED or may be related to fat mass.

In arthropod community ecology, species richness studies tend to be prioritised over those investigating patterns of abundance. Consequently, the biotic and abiotic drivers of arboreal arthropod abundance are still relatively poorly known. In this cross-continental study, we employ a theoretical framework in order to examine patterns of covariance among herbivorous and predatory arthropod guilds. Leaf-chewing and leaf-mining herbivores, and predatory ants and spiders, were censused on > 1000 trees in nine 0.1 ha forest plots. After controlling for tree size and season, we found no negative pairwise correlations between guild abundances per plot, suggestive of weak signals of both inter-guild competition and top-down regulation of herbivores by predators. Inter-guild interaction strengths did not vary with mean annual temperature, thus opposing the hypothesis that biotic interactions intensify towards the equator. We find evidence for the bottom-up limitation of arthropod abundances via resources and abiotic factors, rather than for competition and predation. publishedVersion

Conservation status and management priorities are often informed by population trends. Trend estimates can be derived from population surveys or models, but both methods are associated with sources of uncertainty. Many Arctic-breeding shorebirds are thought to be declining based on migration and/or overwintering population surveys, but data are lacking to estimate the trends of some shorebird species. In addition, for most species, little is known about the stage(s) at which population bottlenecks occur, such as breeding vs. nonbreeding periods. We used previously published and unpublished estimates of vital rates to develop the first large-scale population models for 6 species of Arctic-breeding shorebirds in North America, including separate estimates for 3 subspecies of Dunlin. We used the models to estimate population trends and identify life stages at which population growth may be limited. Our model for the arcticola subspecies of Dunlin agreed with previously published information that the subspecies is severely declining. Our results also linked the decline to the subspecies' low annual adult survival rate, thus potentially implicating factors during the nonbreeding period in the East Asian–Australasian Flyway. However, our trend estimates for all species showed high uncertainty, highlighting the need for more accurate and precise estimates of vital rates. Of the vital rates, annual adult survival had the strongest influence on population trend in all taxa. Improving the accuracy, precision, and spatial and temporal coverage of estimates of vital rates, especially annual adult survival, would improve demographic model-based estimates of population trends and help direct management to regions or seasons where birds are subject to higher mortality.LAY SUMMARYDocumenting population trends is essential for evaluating the conservation status of wild species such as Arctic-breeding shorebirds.Trends can be estimated with population surveys or by predicting population growth based on survival rates and fecundity, but both methods are challenging, especially for species with large or remote geographic distributions.We used recent broad-scale estimates of survival and fecundity to develop population models for 6 species of Arctic-breeding shorebirds.The arcticola subspecies of Dunlin is likely in severe decline, but our trend estimates for all species showed high uncertainty.Uncertainty around the values of annual adult survival rates was a key driver of the uncertainty around the trend estimates.Our work highlights the need for better estimates of annual adult survival, seasonal survival, juvenile survival, and breeding propensity for these Arctic-breeding shorebirds.

Research has repeatedly shown that ongoing habitat loss and the increasing frequency of extreme climatic events have altered fundamental biological processes, threatening biodiversity and ecosystem functioning worldwide. However, the multitude of interacting factors underlying the impacts of these threats remain poorly understood in tropical forests. This is unfortunate because the majority of terrestrial biodiversity resides in these habitats. The responses of organisms to environmental changes are often studied indirectly, for example, using discrete snapshots at different time periods at the same location. This is due to the challenges of compiling long-term data, especially for invertebrates. Evaluating how functionally important species assemblages will respond to anthropogenic threats requires continuous long-term monitoring. This is vital for arthropods because they are responsible for crucial ecosystem services and human food security. Here, we review existing arthropod monitoring schemes and consider some innovative avenues for future research that promise to improve monitoring of this important group in tropical systems.

BACKGROUND Vertical transmission is the major cause of pediatric hepatitis C virus (HCV) infection. The objective of this study was to better understand HCV pathogenesis in pregnant women and provide insights into risk factors and mechanisms involved in vertical transmission. METHODS Evolutionary dynamics of HCV variant spectra and HCV-specific neutralizing antibody responses were examined using high-throughput sequencing and pseudoparticle-based assays in pregnant women monoinfected with HCV (n = 17) or coinfected with HCV and human immunodeficiency virus (HIV)-1 (n = 15). RESULTS Overall, statistically significant associations were found between HCV quasispecies diversity, selective pressure exerted on the HCV E2 envelope protein, and neutralizing activity of maternal immunoglobulins. Women with low quasispecies diversity displayed significantly higher mean aspartate aminotransferase and alanine aminotransferase levels throughout pregnancy, but this difference was restricted to monoinfected participants. Low quasispecies diversity and inefficient neutralizing activity were also significantly associated with vertical transmission, but only in the monoinfected group. CONCLUSIONS These results indicate that maternal neutralizing antibody responses play a role in the prevention of vertical HCV transmission, but not in presence of HIV-1 coinfection, and suggest that the mechanism of vertical transmission may be different between monoinfected and coinfected women. These findings could inform management strategies for the prevention of vertical HCV transmission.

MicroRNAs are potent regulators of gene expression that have been widely implicated in reproduction and embryo development. Recent studies have demonstrated that miR-21, a microRNA extensively studied in the context of disease, is important in multiple facets of reproductive biology including folliculogenesis, ovulation, oocyte maturation and early mammalian development. Surprisingly, little is known about the mechanisms that regulate miR-21 and no studies have characterized these regulatory pathways in cumulus-oocyte complexes (COCs). We therefore investigated miR-21 in an in vitro model of bovine oocyte maturation. Levels of the primary transcript of miR-21 (pri-miR-21) and mature miR-21 increased markedly in COCs over the maturation period. Cloning of the bovine pri-miR-21 gene and promoter by 5′3′RACE (rapid amplification of cDNA ends) revealed a highly conserved region immediately upstream of the transcription start site and two alternatively-spliced variants of pri-miR-21. The promoter region contained several putative transcription factor binding sites, including two for signal transducer and activator of transcription 3 (STAT3). Mutation of these sites significantly decreased both the intrinsic activity of pri-miR-21 promoter-luciferase constructs and the response to leukemia inhibitory factor (LIF) (a STAT3 activator) in cultured MCF7 cells. In COCs, treatment with a STAT3 pathway inhibitor markedly decreased pri-miR-21 expression and prevented cumulus expansion. Pri-miR-21 expression was also inhibited by the protein synthesis inhibitor cycloheximide, suggesting that a protein ligand or signaling cofactor synthesized during maturation is necessary for transcription. Together these studies represent the first investigation of signaling pathways that directly influence miR-21 expression in bovine oocytes and cumulus cells.

Many north American shorebird populations are declining. it is therefore urgent to identify major sites used during their annual cycle to achieve effective conservation measures. our objective was to expand some aspects of the knowledge base needed to assess the ecological value of the St. Lawrence River Estuary for shorebird conservation. Here, we present the results of the most intensive shorebird survey ever conducted in the St. Lawrence River Estuary during fall migration. Surveys were conducted between St-Jean-Port-Joli and St-Simon-sur-Mer, Quebec, Canada, in 2011 and 2012, from late June/early July through late november, corresponding to the migration period of all species potentially present in the study area. The Semipalmated Sandpiper (Calidris pusilla) was one of the two most abundant species during both years of our study (most abundant species, followed by Dunlin [Calidris alpina] and Black-bellied Plover [Pluvialis squatarola] in 2011; second to Blackbellied Plover in 2012). Considering the entire shorebird community, abundance of individuals peaked in early September. Peak abundance occurred earlier for adults than for juveniles. For most species, juveniles largely outnumbered adults. Juveniles were relatively less abundant in 2012 than in 2011. This reflected a general trend observed in northeastern north America between those years, suggesting a lower breeding success in 2012. Given its importance as a staging site for juvenile birds (study area used annually by up to a few hundred thousand shorebirds) and therein, its conservation value, we recommend that the St. Lawrence River Estuary should be included within the Western Hemisphere Shorebird Reserve network.

Many Arctic shorebird populations are declining, and quantifying adult survival and the effects of anthropogenic factors is a crucial step toward a better understanding of population dynamics. We used a recently developed, spatially explicit Cormack–Jolly–Seber model in a Bayesian framework to obtain broad-scale estimates of true annual survival rates for 6 species of shorebirds at 9 breeding sites across the North American Arctic in 2010–2014. We tested for effects of environmental and ecological variables, study site, nest fate, and sex on annual survival rates of each species in the spatially explicit framework, which allowed us to distinguish between effects of variables on site fidelity versus true survival. Our spatially explicit analysis produced estimates of true survival rates that were substantially higher than previously published estimates of apparent survival for most species, ranging from S = 0.72 to 0.98 across 5 species. However, survival was lower for the arcticola subspecies of ...

Inactivation of the tumor suppressor gene, von Hippel-Lindau (VHL), is known to play an important role in the development of sporadic clear cell renal cell carcinomas (ccRCCs). Even if available targeted therapies for metastatic RCCs (mRCCs) have helped to improve progression-free survival rates, they have no durable clinical response. We have previously shown the feasibility of specifically targeting the loss of VHL with the identification of a small molecule, STF-62247. Understanding its functionality is crucial for developing durable personalized therapeutic agents differing from those available targeting hypoxia inducible factor (HIF-) pathways. By using SILAC proteomics, we identified 755 deregulated proteins in response to STF-62247 that were further analyzed by ingenuity pathway analysis (IPA). Bioinformatics analyses predicted alterations in 37 signaling pathways in VHL-null cells in response to treatment. Validation of some altered pathways shows that STF-62247's selectivity is linked to an important inhibition of mTORC1 activation in VHL-null cells leading to protein synthesis arrest, a mechanism differing from two allosteric inhibitors Rapamycin and Everolimus. Altogether, our study identified signaling cascades driving STF-62247 response and brings further knowledge for this molecule that shows selectivity for the loss of VHL. The use of a global SILAC approach was successful in identifying novel affected signaling pathways that could be exploited for the development of new personalized therapeutic strategies to target VHL-inactivated RCCs.

In this study, newly identified host interactors of hepatitis C virus (HCV) proteins were assessed for a role in modulating the innate immune response. The analysis revealed enrichment for components of the nuclear transport machinery and the crucial interaction with NS3/4A protein in suppression of interferon‐β (IFNB1) induction. Using a comprehensive microscopy‐based high‐content screening approach combined to the gene silencing of nuclear transport factors, we showed that NS3/4A‐interacting proteins control the nucleocytoplasmic trafficking of IFN regulatory factor 3 (IRF3) and NF‐κB p65 upon Sendai virus (SeV) infection. Notably, importin β1 (IMPβ1) knockdown—a hub protein highly targeted by several viruses—decreases the nuclear translocation of both transcription factors and prevents IFNB1 and IFIT1 induction, correlating with a rapid increased of viral proteins and virus‐mediated apoptosis. Here we show that NS3/4A triggers the cleavage of IMPβ1 and inhibits nuclear transport to disrupt IFNB1 production. Importantly, mutated IMPβ1 resistant to cleavage completely restores signaling, similar to the treatment with BILN 2061 protease inhibitor, correlating with the disappearance of cleavage products. Overall, the data indicate that HCV NS3/4A targeting of IMPβ1 and related modulators of IRF3 and NF‐κB nuclear transport constitute an important innate immune subversion strategy and inspire new avenues for broad‐spectrum antiviral therapies., Hepatitis C virus (HCV) hijacks the cellular host machinery to promote replication and to evade immune response. Using a microscopy‐based High Content Screening (HCS) assay, we demonstrated that HCV‐host interactors involved in nuclear transport are crucial for IRF3 and NFκB‐p65 signaling of IFNB1 response. To subvert innate immunity, NS3/4A interacts and cleaves IMPβ1, a key nucleocytoplasmic transport receptor, to prevent nuclear translocation of IRF3 and NFκB‐p65 transcription factors. Future studies will confirm if IMPβ1 is a prime target for several viruses to evade host defense.

Various physiological factors suspected to govern or be influenced by growth or feed intake of brook charr (80–120 g) were examined under long and short fasting periods during the year. A control (fed to satiation) was included. During winter, fasting (14 and 28 days) followed by refeeding led to a complete compensation. In summer, longer fasting (39 and 61 days) was applied to exacerbate the physiological response. Compensatory growth was observed in the restricted groups, and overall, adjustments/variations in growth and physiological indicators (feed conversion ratio, organosomatic index, enzymatic activities [CS, TRY, CHY]) were more pronounced. Degree of compensation reached was positively related to the deprivation duration. The summer experiment clearly suggests that compensatory growth takes place in two stages after a long starvation period (61 days): (1) restoration of the digestive system (PSI) followed by enzyme activities (trypsin and chymotrypsin) and (2) rebuilding of somatic tissues.

The increasing use of plant viruses for the development of new vaccines and immunotherapy approaches poses questions regarding the mechanism by which the mammalian immune system recognizes these viruses. For example, although natural Abs (NA) and complement are key components of the innate immune system involved in the opsonization, phagocytosis, and destruction of microorganisms infecting mammals, their implication in plant virus recognition and immunogenicity is not well defined. In this study, we address the involvement of NA and the complement system in the activation of innate immunity through engagement of TLR7 with papaya mosaic virus (PapMV)-like nanoparticles. We demonstrate that NA, although binding to PapMV, are not involved in its recognition by the immune system. On the other hand, C3 strongly binds to PapMV nanoparticles and its depletion significantly reduces PapMV’s interaction with immune cells. Unexpectedly, however, we observed increased immune cell activation following administration of PapMV to complement-depleted mice. TLR7 activation by PapMV in the absence of C3 induced higher IFN-α production, resulting in superior immune cell activation and increased immunotherapeutic properties. In conclusion, in this study we established the involvement of the complement system in the recognition and the phagocytosis of PapMV nanoparticles and identified an unsuspected role for C3 in regulating the production of IFN-α following TLR7 activation.