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Municipal wastewater is a large source of pollution to Canadian waters, yet its effects on Arctic marine ecosystems remains relatively unknown. We characterized the impacts of municipal wastewater from a growing northern community, Iqaluit, Nunavut, on the Arctic truncate soft-shell clam, Mya truncata. Clams were sampled from six locations that varied in proximity to the wastewater treatment plant, and shell biogeochemical analysis revealed that clams nearest the wastewater treatment plant had slower growth rates, lower carbon and oxygen stable isotope ratios, and elevated concentrations of copper and lead. A parallel analysis on mRNA expression profiles characterized M. truncata’s physiological response to wastewater effluent. Clams nearest the wastewater treatment plant had significantly lower mRNA expression of genes associated with metabolism, antioxidants, molecular chaperones, and phase I and II detoxification, but had heightened mRNA expression in genes coding for enzymes that bind and remove contaminants. These results demonstrated a biological response to Iqaluit’s wastewater effluent and highlight M. truncata’s potential to act as a biomonitor of municipal wastewater along Arctic coastlines in Canada.

The pathways regulated in ectomycorrhizal (EcM) plant hosts during the establishment of symbiosis are not as well understood when compared to the functional stages of this mutualistic interaction. Our study used the EcM host Eucalyptus grandis to elucidate symbiosis-regulated pathways across the three phases of this interaction. Using a combination of RNA sequencing and metabolomics we studied both stage-specific and core responses of E. grandis during colonization by Pisolithus microcarpus. Using exogenous manipulation of the abscisic acid (ABA), we studied the role of this pathway during symbiosis establishment. Despite the mutualistic nature of this symbiosis, a large number of disease signalling TIR-NBS-LRR genes were induced. The transcriptional regulation in E. grandis was found to be dynamic across colonization with a small core of genes consistently regulated at all stages. Genes associated to the carotenoid/ABA pathway were found within this core and ABA concentrations increased during fungal integration into the root. Supplementation of ABA led to improved accommodation of P. microcarpus into E. grandis roots. The carotenoid pathway is a core response of an EcM host to its symbiont and highlights the need to understand the role of the stress hormone ABA in controlling host-EcM fungal interactions.

Management of protected species is difficult when objectives include the recovery of both predator and its prey. Ideally, identifying trade-offs between competing objectives involves evaluating management alternatives with a quantitative model that integrates information on both species, but data are often limited. We used new predator diet data and simulation modeling to update our understanding of seal predation on juvenile Chinook (Oncorhynchus tshawytscha) and coho salmon (Oncorhynchus kisutch) in the Puget Sound. Under prey size assumptions used by previous studies, estimates suggest predation could be a significant source of mortality for Chinook salmon (mean: 37% of ocean age-0 juveniles), but varied considerably among years (range of median estimates: 22%–49%). However, when we estimated prey size from otoliths recovered from seal scats, the impact (numbers of fish consumed) decreased by 71%. Predation on coho salmon was estimated to be relatively low under both scenarios (6%–8% of ocean age-0 juveniles) with a 21% decrease in consumption using otolith-derived prey size. Our analysis highlights the importance of updating model inputs and re-evaluating assumptions of multi-species models used for ecosystem-based fisheries management.

Effective management of freshwater fish habitat is essential to supporting healthy aquatic ecosystems and sustainable fisheries. In Canada, recent changes to the Fisheries Act enhanced the protection of fish habitat, but application of those provisions relies on sound scientific evidence. We employed collaborative research prioritization methods to identify scientific research questions that, if addressed, would significantly advance the management of freshwater fish habitat in Canada. This list was generated by a diverse group of freshwater fish experts, including substantial contributions from practitioners who administer provisions of the Fisheries Act. The research questions generated in this study identify priority topics for future research, while highlighting issues that could be addressed with different funding models. As a result, this study should support evidence-based management of Canada’s aquatic resources by identifying scientific knowledge gaps faced by practitioners, and suggesting mechanisms to address them. Given the important contribution of Canadian freshwater systems to global ecosystem values, and the similar scientific challenges facing fish habitat managers in other jurisdictions, this study is likely to have broad applicability.

In Manitoba, Canada, wild lake sturgeon (Acipenser fulvescens) populations exist along a latitudinal gradient and are reared in hatcheries to bolster threatened populations. We reared two populations of lake sturgeon, one from each of the northern and southern ends of Manitoba and examined the effects of typical hatchery temperatures (16°C) as well as 60-day acclimation to elevated rearing temperatures (20°C) on mortality, growth and condition throughout early development. Additionally, we examined the cold shock response, which may be induced during stocking, through the hepatic mRNA expression of genes involved in the response to cold stress and homeoviscous adaptation (HSP70, HSP90a, HSP90b, CIRP and SCD). Sturgeon were sampled after 1 day and 1 week following stocking into temperatures of 8, 6 and 4°C in a controlled laboratory environment. The southern population showed lower condition and higher mortality during early life than the northern population while increased rearing temperature impacted the growth and condition of developing northern sturgeon. During the cold shock, HSP70 and HSP90a mRNA expression increased in all sturgeon treatments as stocking temperature decreased, with higher expression observed in the southern population. Expression of HSP90b, CIRP and SCD increased as stocking temperature decreased in northern sturgeon with early acclimation to 20°C. Correlation analyses indicated the strongest molecular relationships were in the expression of HSP90b, CIRP and SCD, across all treatments, with a correlation between HSP90b and body condition in northern sturgeon with early acclimation to 20°C. Together, these observations highlight the importance of population and rearing environment throughout early development and on later cellular responses induced by cold stocking temperatures.

In demyelinating diseases, such as multiple sclerosis, primary loss of myelin and subsequent neuronal degeneration throughout the CNS impair patient functionality. While the importance of mechanistic target of rapamycin (mTOR) signaling during developmental myelination is known, no studies have yet directly examined the function of mTOR signaling specifically in the oligodendrocyte (OL) lineage during remyelination. Here, we conditionally deleted Mtor from adult oligodendrocyte precursor cells (OPCs) using Ng2-Cre(ERT) in male adult mice to test its function in new OLs responsible for remyelination. During early remyelination after cuprizone-induced demyelination, mice lacking mTOR in adult OPCs had unchanged OL numbers but thinner myelin. Myelin thickness recovered by late-stage repair, suggesting a delay in myelin production when Mtor is deleted from adult OPCs. Surprisingly, loss of mTOR in OPCs had no effect on efficiency of remyelination after lysophosphatidylcholine lesions in either the spinal cord or corpus callosum, suggesting that mTOR signaling functions specifically in a pathway dysregulated by cuprizone to promote remyelination efficiency. We further determined that cuprizone and inhibition of mTOR cooperatively compromise metabolic function in primary rat OLs undergoing differentiation. Together, our results support the conclusion that mTOR signaling in OPCs is required to overcome the metabolic dysfunction in the cuprizone-demyelinated adult brain. SIGNIFICANCE STATEMENT Impaired remyelination by oligodendrocytes contributes to the progressive pathology in multiple sclerosis, so it is critical to identify mechanisms of improving remyelination. The goal of this study was to examine mechanistic target of rapamycin (mTOR) signaling in remyelination. Here, we provide evidence that mTOR signaling promotes efficient remyelination of the brain after cuprizone-mediated demyelination but has no effect on remyelination after lysophosphatidylcholine demyelination in the spinal cord or brain. We also present novel data revealing that mTOR inhibition and cuprizone treatment additively affect the metabolic profile of differentiating oligodendrocytes, supporting a mechanism for the observed remyelination delay. These data suggest that altered metabolic function may underlie failure of remyelination in multiple sclerosis lesions and that mTOR signaling may be of therapeutic potential for promoting remyelination.

Background. Outbreaks of mosquito-borne arboviral diseases including dengue virus (DENV), Zika virus (ZIKV), yellow fever virus (YFV) and chikungunya virus (CHIKV) have recently occurred in the Caribbean. The geographical range of the principal vectors responsible for transmission, Aedes (Ae.) aegypti and Ae. albopictus are increasing and greater mosquito surveillance is needed in the Caribbean given international tourism is so prominent. The island of Saint Lucia has seen outbreaks of DENV and CHIKV in the past five years but vector surveillance has been limited with the last studies dating back to the late 1970s. Natural disasters have changed the landscape of Saint Lucia and the island has gone through significant urbanisation. Methods. In this study, we conducted an entomological survey of Ae. aegypti and Ae. albopictus distribution across the island and analysed environmental parameters associated with the presence of these species in addition to screening for medically important arboviruses and other flaviviruses. Results. Although we collected Ae. aegypti across a range of sites across the island, no Ae. albopictus were collected despite traps being placed in diverse ecological settings. The number of Ae. aegypti collected was significantly associated with higher elevation, and semi-urban settings yielded female mosquito counts per trap-day that were five-fold lower than urban settings. Screening for arboviruses revealed a high prevalence of cell-fusing agent virus (CFAV). Conclusions. Outbreaks of arboviruses transmitted by Ae. aegypti and Ae. albopictus have a history of occurring in small tropical islands and Saint Lucia is particularly vulnerable given the limited resources available to undertake vector control and manage outbreaks. Surveillance strategies can identify risk areas for predicting future outbreaks. Further research is needed to determine the diversity of current mosquito species, investigate insect-specific viruses, as well as pathogenic arboviruses, and this should also be extended to the neighbouring smaller Caribbean islands.

The aim of this investigation was to determine if acute or repeated applications of ischemic preconditioning (IPC) could enhance the recovery process, following exercise induced muscle damage (EIMD).Randomized control trial.Twenty-three healthy males were familiarised with the muscle damaging protocol (five sets of 20 drop jumps from a 0.6 m box) and randomly allocated to one of three groups: SHAM (3 × 5 min at 20 mmHg), Acute IPC (3 × 5 min at 220 mmHg) and Repeated IPC (3 days x 3 × 5 min at 220 mmHg). The indices of muscle damage measured included creatine kinase concentration ([CK]), thigh swelling, delayed onset muscle soreness, counter movement jumps (CMJ) and maximal voluntary isometric contraction (MVIC).Both acute and repeated IPC improved recovery in MVIC versus SHAM. Repeated IPC led to a faster MVIC recovery at 48 h (101.5%) relative to acute IPC (92.6%) and SHAM (84.4%) (P 0.05). Less swelling was found for both acute and repeated IPC vs. SHAM (P 0.05) but no group effects were found for CMJ, soreness or [CK] responses (P 0.05).Taken together, repeated IPC can enhance recovery time of MVIC more than an acute application, and both reduce swelling following EIMD, relative to a SHAM condition.

The invasive rainbow smelt (Osmerus mordax) was an abundant food source for Lake Winnipeg walleye (Sander vitreus), especially in the north basin of the lake, until the smelt’s collapse in approximately 2013. We quantified changing length-at-age (≈ growth rates) and relative mass (≈ body condition) in Lake Winnipeg walleye caught for a gillnet index data set. Here, walleye showed smaller length-at-age, particularly young fish in the north basin, over time. This approach to assessing growth suggests a constraint in the north basin fish, possibly a nutritional limitation between 2017 and 2018, that was not present in the south. We then analyzed a separate group of walleye (≥452 mm in fork length) sampled in 2017 as part of a large-scale tracking study, which had a similar slope in length-mass relationship to large walleye caught in that year for the gillnet index data. A panel of metabolites in whole blood samples associated with amino acid metabolism and protein turnover was compared. These metabolites revealed elevated essential amino acids in fish caught in the Dauphin River, and suggest that protein degradation may be elevated in north basin walleye. Therefore, based on both growth estimates and metabolites associated with protein balance, we suggest there were spatially distinct separations affecting Lake Winnipeg walleye with decreased nutritional status of walleye in the north basin of Lake Winnipeg being of particular concern.

Description, Child PAX8 methylation is associated with thyroid volume and function and influenced by maternal periconceptional nutrition., PAX8 is a key thyroid transcription factor implicated in thyroid gland differentiation and function, and PAX8 gene methylation is reported to be sensitive to the periconceptional environment. Using a novel recall-by-epigenotype study in Gambian children, we found that PAX8 hypomethylation at age 2 years is associated with a 21% increase in thyroid volume and an increase in free thyroxine (T4) at 5 to 8 years, the latter equivalent to 8.4% of the normal range. Free T4 was associated with a decrease in DXA-derived body fat and bone mineral density. Furthermore, offspring PAX8 methylation was associated with periconceptional maternal nutrition, and methylation variability was influenced by genotype, suggesting that sensitivity to environmental exposures may be under partial genetic control. Together, our results demonstrate a possible link between early environment, PAX8 gene methylation and thyroid gland development and function, with potential implications for early embryonic programming of thyroid-related health and disease.

The fish embryo acute toxicity (FET) test is known to be less sensitive than the fish acute test for some chemicals, including neurotoxicants. Thus, there is an interest in identifying additional endpoints that can improve FET test performance. The goal of this project was to advance alternative toxicity testing methods by determining whether select developmental abnormalities-snout-vent length, eye size, and pericardial area-are linked to adverse alterations in ecologically-relevant behaviors and delayed mortality. Fathead minnow (Pimephales promelas) FET tests were conducted with 3,4-dicholoroaniline, cadmium, and perfluorooctanesulfonic acid (PFOS) and developmental abnormalities were quantified. Surviving eleutheroembryos were reared in clean water to 14 days post fertilization (dpf), during which time behaviors and mortality were evaluated. None of the abnormalities evaluated were predictive of behavioral alterations; however, embryos with ≥14% reductions in length or ≥3.54-fold increases in pericardial area had an 80% chance of mortality by 14 dpf. When these abnormalities were used as markers of mortality, the LC50s for cadmium and PFOS were less than those calculated using only standardized FET test endpoints and similar to those obtained via larval fish tests, indicating that the snout-vent length and pericardial area warrant consideration as standard FET test endpoints.

Next-generation sequencing platforms are being increasingly applied in clinical genetic settings for evaluation of families with suspected heritable disease. These platforms potentially improve the diagnostic yield beyond that of disease-specific targeted gene panels, but also increase the number of rare or novel genetic variants that may confound precise diagnostics. Here, we describe a functional testing approach used to interpret the results of whole exome sequencing (WES) in a family presenting with syncope and sudden death. One individual had a prolonged QT interval on electrocardiogram (ECG) and carried a diagnosis of long QT syndrome (LQTS), but a second individual did not meet criteria for LQTS. Filtering WES results for uncommon variants with arrhythmia association identified four for further analyses. In silico analyses indicated that two of these variants, KCNH2 p.(Cys555Arg) and KCNQ1 p.(Arg293Cys), were likely to be causal in this family's LQTS. We subsequently performed functional characterization of these variants in a heterologous expression system. The expression of KCNQ1-Arg293Cys did not show a deleterious phenotype but KCNH2-Cys555Arg demonstrated a loss-of-function phenotype that was partially dominant. Our stepwise approach identified a precise genetic etiology in this family, which resulted in the establishment of a LQTS diagnosis in the second individual as well as an additional asymptomatic family member, enabling personalized clinical management. Given its ability to aid in the diagnosis, the application of functional characterization should be considered as a value adjunct to in silico analyses of WES.

The spike protein of severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) is critical for virus infection through the engagement of the human ACE2 protein1 and is a major antibody target. Here we show that chronic infection with SARS-CoV-2 leads to viral evolution and reduced sensitivity to neutralizing antibodies in an immunosuppressed individual treated with convalescent plasma, by generating whole-genome ultra-deep sequences for 23 time points that span 101 days and using in vitro techniques to characterize the mutations revealed by sequencing. There was little change in the overall structure of the viral population after two courses of remdesivir during the first 57 days. However, after convalescent plasma therapy, we observed large, dynamic shifts in the viral population, with the emergence of a dominant viral strain that contained a substitution (D796H) in the S2 subunit and a deletion (ΔH69/ΔV70) in the S1 N-terminal domain of the spike protein. As passively transferred serum antibodies diminished, viruses with the escape genotype were reduced in frequency, before returning during a final, unsuccessful course of convalescent plasma treatment. In vitro, the spike double mutant bearing both ΔH69/ΔV70 and D796H conferred modestly decreased sensitivity to convalescent plasma, while maintaining infectivity levels that were similar to the wild-type virus.The spike substitution mutant D796H appeared to be the main contributor to the decreased susceptibility to neutralizing antibodies, but this mutation resulted in an infectivity defect. The spike deletion mutant ΔH69/ΔV70 had a twofold higher level of infectivity than wild-type SARS-CoV-2, possibly compensating for the reduced infectivity of the D796H mutation. These data reveal strong selection on SARS-CoV-2 during convalescent plasma therapy, which is associated with the emergence of viral variants that show evidence of reduced susceptibility to neutralizing antibodies in immunosuppressed individuals.

De novo heterozygous variants in the brain-specific transcription factor Neuronal Differentiation Factor 2 (NEUROD2) have been recently associated with early-onset epileptic encephalopathy and developmental delay. Here, we report an adolescent with developmental delay without seizures who was found to have a novel de novo heterozygous NEUROD2 missense variant, p.(Leu163Pro). Functional testing using an in vivo assay of neuronal differentiation in Xenopus laevis tadpoles demonstrated that the patient variant of NEUROD2 displays minimal protein activity, strongly suggesting a loss of function effect. In contrast, a second rare NEUROD2 variant, p.(Ala235Thr), identified in an adolescent with developmental delay but lacking parental studies for inheritance, showed normal in vivo NEUROD2 activity. We thus provide clinical, genetic, and functional evidence that NEUROD2 variants can lead to developmental delay without accompanying early-onset seizures, and demonstrate how functional testing can complement genetic data when determining variant pathogenicity.

Water is being a basic necessity for the existence of life on this planet. In the existing system, water management system exists with a supply of water from panchayat to a group of people or village in a particular time period which is unknown and therefore it may cause a discomfort for the people to get water if they are unavailable at that time. In the proposed system, it aims to develop a water management system in which an automatic GSM alert is used to intimate the time of supply of water to a particular region priory and also an ultrasonic algae prevention system is attached with it the main tank to prevent the algae formation. In the part of automatic GSM alert, the water supply will be notified to an individual through their mobile which makes them aware of time of supply and avoids the limitations of the existing system. Ultrasonic algae prevention system is based on the proven fact that ultrasonic braves prevents the formation of molecules from an atom which is the major reason for the algae formation in tank so that ultrasonic sensor is used to pass waves at regular intervals to avoid formation of algae in the water tank

Capacity to cope with warming temperatures is a key determining factor of species' persistence under global climate change. Many successful invasive species have heightened thermal tolerance relative to their native counterparts, which may provide competitive advantages for habitat utilization and resource acquisition under warming scenarios, ultimately contributing to radically altered community composition. Enhanced transcriptional plasticity may be an important factor conferring superior abilities to cope with environmental stress, but the molecular mechanisms driving key differences of organismal traits in invasive versus native species are not well known. Although it is predicted that established invaders will evolve canalized phenotypes well‐adapted to new environments, it is not clear whether the same expectations are true for invaders of variable thermal environments or under climate warming scenarios where abilities to cope with fluctuating and increasing temperatures may provide fitness advantages. Here, we compare a highly successful invasive fish and a sympatric endangered native fish living in a dynamic estuarine environment that is projected to warm under climate change. We linked organismal physiological limits with global transcriptional responses at multiple common relative and absolute temperature thresholds and determined that heightened thermal tolerance of invasive Inland Silversides (Menidia beryllina) is associated with transcriptional changes that are greater both in the number of genes and the magnitude of response relative to native Delta Smelt (Hypomesus transpacificus). Modulated genes contributed to the enrichment of biological processes that differed between species and generally increased with temperature. These results are in concordance with the hypothesis that transcriptional plasticity may play a key role in determining population persistence, species interactions, and shaping community assemblages under climate change. Future studies encompassing a wider range of species and taxa are needed to determine whether this is a general pattern found between native and invasive species more broadly.

Background Current recommendations for monitoring disease progression and response to treatment in humans with multiple myeloma include evaluation of serum paraprotein (M-protein) concentration. Densitometry, species-specific radial immunodiffusion (RID) and ELISA methods can be used to quantify M-proteins. Objective Retrospectively evaluate use of the International Myeloma Working Group (IMWG) response criteria for humans in dogs with multiple myeloma. Animals Sixteen dogs with a diagnosis of multiple myeloma, M-protein documented by serum protein electrophoresis (SPE) and immunofixation (IF) in an initial sample and subsequent electrophoretic evaluation of serial samples. Methods Retrospectively, densitometric M-proteins, RID and globulins were measured and characterized according to IMWG criteria. Available clinical history was reviewed. Overall survival time (OST) was calculated from initial electrophoretic evaluation to death or last contact. Results All cases received some form of nonstandardized chemotherapy. Complete response (CR), a lack of detectable M-protein by SPE and IF, was documented in 1 case. Median survival was longer for dogs that attained ≥90% densitometric M-protein reduction (630 days) than for those that did not attain at least 50% reduction in densitometric M-protein (284 days; log rank P = .006). Five dogs were defined as having progressive disease (M-protein increase of >25% and at least 0.5 g/dL from nadir), which correlated with concurrent or subsequent clinical deterioration. Response criteria categorized by serum globulins or RID was not correlated with OST or clinical findings. Conclusions and clinical importance Densitometric M-protein characterized using IMWG response criteria correlated with OST and clinical findings. Densitometric M-protein detection should be used to monitor dogs with multiple myeloma.

Despite the promising applications of genome-wide information to conservation, the field of conservation genomics remains hindered by a research-practice gap. Identifying the benefits from genomics in relation to fish conservation planning and decision-making could contribute to bridging this gap. The goals of our study were twofold. First, we reviewed the fish conservation genomic literature to determine how genomic information has been used to inform conservation decision making; and second, we examined how genomic information can be linked to an existing conservation decision framework. Our review showed that, as fish conservation genomics studies accumulate over time, collaborations between researchers and conservation practitioners are becoming increasingly frequent. While the field is dominated by studies of economically important families (e.g. salmonids, acipenserids) in first-world countries (North America, Europe), it has a broad taxonomic coverage where species of both local and global conservation concern are well represented. We also show that genomic information can readily be harnessed to guide decisions within existing conservation decision frameworks, from the conceptualization (identification of conservation targets and threats) to the implementation and the monitoring of conservation actions. In addition, our review identifies some limitations related to genomic inferences for conservation and proposes solutions to address these uncertainties and improve communication between conservation genomic scientists and practitioners. For genomic researchers, we outline how conservation decisions are made; for practitioners, we illustrate how genomic information can inform decision-making.

Converging evidence implicates redox dysregulation as a pathological mechanism driving the emergence of psychosis. Increased oxidative damage and decreased capacity of intracellular redox modulatory systems are consistent findings in persons with schizophrenia as well as in persons at clinical high risk who subsequently developed frank psychosis. Levels of glutathione, a key regulator of cellular redox status, are reduced in the medial prefrontal cortex, striatum, and thalamus in schizophrenia. In humans with schizophrenia and in rodent models recapitulating various features of schizophrenia, redox dysregulation is linked to reductions of parvalbumin containing gamma-aminobutyric acid (GABA) interneurons and volumes of their perineuronal nets, white matter abnormalities, and microglia activation. Importantly, the activity of transcription factors, kinases, and phosphatases regulating diverse aspects of neurodevelopment and synaptic plasticity varies according to cellular redox state. Molecules regulating interneuron function under redox control include NMDA receptor subunits GluN1 and GluN2A as well as KEAP1 (regulator of transcription factor NRF2). In a rodent schizophrenia model characterized by impaired glutathione synthesis, the Gclm knockout mouse, oxidative stress activated MMP9 (matrix metalloprotease 9) via its redox-responsive regulatory sites, causing a cascade of molecular events leading to microglia activation, perineural net degradation, and impaired NMDA receptor function. Molecular pathways under redox control are implicated in the etiopathology of schizophrenia and are attractive drug targets for individualized drug therapy trials in the contexts of prevention and treatment of psychosis.

Recent studies have utilized the fathead minnow (Pimephales promelas) to explore the immunotoxic effects associated with a variety of environmental contaminants in the absence of immunological stimuli. Though this approach allows for alterations in the resting immune system to be detected, previous evidence suggests that many immunotoxic effects may only manifest in the activated immune system. However, basic immune responses to pathogens have not been well described in this species. To expand the utility of the fathead minnow as a model for immunotoxicity testing, a more comprehensive understanding of the activated immune system is required. As such, the main goal of this study was to characterize the transcriptomic response to pathogen infection in the fathead minnow using RNA sequencing. To achieve this goal, female fathead minnows were intraperitoneally injected with either Hank's Balanced Salt Solution (sham-injected) or Yersinia ruckeri (pathogen-injected). Eight hours following injection, fish were sacrificed for the assessment of general morphological (i.e., mass, length, condition factor, hepatic index) and immunological (i.e., leukocyte counts, spleen index) endpoints. To assess the molecular immune response to Y. ruckeri, kidney tissue was collected for transcriptomic analysis. A comparison of sham- and pathogen-injected fish revealed that >1800 genes and >500 gene networks were differentially expressed.Gene networks associated with inflammation, innate immunity, complement, hemorrhaging and iron absorption are highlighted and their utility within the context of immunotoxicity is discussed. These data reveal pathogen-related molecular endpoints to improve data interpretation of future studies utilizing the fathead minnow as a model for immunotoxicity.

BackgroundCilia are dynamic cellular extensions that generate and sense signals to orchestrate proper development and tissue homeostasis. They rely on the underlying polarisation of cells to participate in signalling. Cilia dysfunction is a well-known cause of several diseases that affect multiple organ systems including the kidneys, brain, heart, respiratory tract, skeleton and retina.MethodsAmong individuals from four unrelated families, we identified variants in discs large 5 (DLG5) that manifested in a variety of pathologies. In our proband, we also examined patient tissues. We depleted dlg5 in Xenopus tropicalis frog embryos to generate a loss-of-function model. Finally, we tested the pathogenicity of DLG5 patient variants through rescue experiments in the frog model.ResultsPatients with variants of DLG5 were found to have a variety of phenotypes including cystic kidneys, nephrotic syndrome, hydrocephalus, limb abnormalities, congenital heart disease and craniofacial malformations. We also observed a loss of cilia in cystic kidney tissue of our proband. Knockdown of dlg5 in Xenopus embryos recapitulated many of these phenotypes and resulted in a loss of cilia in multiple tissues. Unlike introduction of wildtype DLG5 in frog embryos depleted of dlg5, introduction of DLG5 patient variants was largely ineffective in restoring proper ciliation and tissue morphology in the kidney and brain suggesting that the variants were indeed detrimental to function.ConclusionThese findings in both patient tissues and Xenopus shed light on how mutations in DLG5 may lead to tissue-specific manifestations of disease. DLG5 is essential for cilia and many of the patient phenotypes are in the ciliopathy spectrum.

Glucocorticoids have been suggested to be involved in several neuropsychiatric disorders, including depression. One of the possible mechanisms through which glucocorticoids contribute to the development of the depressive symptomatology is via regulation of distinct neurogenic mechanisms in the brain. A preventive or protective approach for these patients might be the use of omega-3 polyunsaturated fatty acids (n-3 PUFAs), eicosapentaenoic acid (EPA) and docosahexaenoic acid (DHA), which are known for they neuroprotective properties. We used the human hippocampal progenitor cell line HPC0A07/03C and pre-treated cells with either EPA or DHA, followed by treatment with the glucocorticoid cortisol either alone, or in co-treatment with the same n-3 PUFA during subsequent 3 days of proliferation and 7 days of differentiation. During proliferation, both EPA and DHA were able to prevent cortisol-induced reduction in proliferation and increase in apoptosis, when used in pre-treatment, and both pre- and co-treatment. During differentiation, EPA was able to prevent cortisol-induced reduction in neurogenesis and increase in apoptosis, when used in pre-treatment, and both pre- and co-treatment only during the proliferation stage; however, DHA required continuous treatment also during the differentiation stage to prevent cortisol-induced reduction in neurogenesis. Using transcriptomic analyses, we showed that both EPA and DHA regulated pathways involved in oxidative stress and immune response [e.g., nuclear factor (erythroid-derived 2)-like 2 (Nrf2), Signal transducer and activator of transcription 3 (STAT3), Interferon (IFN) and Interleukin (IL)-1 signaling], whereas DHA also regulated pathways involved in cell development and neuronal formation [e.g., cAMP-response element binding protein (CREB) signaling]. We provide the first evidence for treatment with both EPA and DHA to prevent cortisol-induced reduction in human hippocampal neurogenesis, and identify novel molecular mechanisms underlying these effects.

RNA sequencing is an effective approach for studying aquatic species yielding both physiological and genomic data. However, its population genetic applications are not well‐characterized. We investigate this possible role for RNA sequencing for population genomics in Lake Winnipeg, Manitoba, Canada, walleye (Sander vitreus). Lake Winnipeg walleye represent the largest component of the second‐largest freshwater fishery in Canada. In the present study, large female walleye were sampled via nonlethal gill biopsy over two years at three spawning sites representing a latitudinal gradient in the lake. Genetic variation from sequenced mRNA was analyzed for neutral and adaptive markers to investigate population structure and possible adaptive variation. We find low population divergence (F ST = 0.0095), possible northward gene flow, and outlier loci that vary latitudinally in transcripts associated with cell membrane proteins and cytoskeletal function. These results indicate that Lake Winnipeg walleye may be effectively managed as a single demographically connected metapopulation with contributing subpopulations and suggest genomic differences possibly underlying observed phenotypic differences. Despite its high cost relative to other genotyping methods, RNA sequencing data can yield physiological in addition to genetic information discussed here. We therefore argue that it is useful for addressing diverse molecular questions in the conservation of freshwater species., Principal components analysis implemented in pcadapt, with color showing site and point shapes showing year collected. Out of 222,634 single nucleotide polymorphisms (SNPs) called from RNA seq data, 386 showed signatures of selection across a latitudinal gradient in Lake Winnipeg, Manitoba, Canada.

Blood sampling through the caudal vasculature is a widely used technique in fish biology for investigating organismal health and physiology. In live fishes, it can provide a quick, easy and relatively non-invasive method for obtaining a blood sample (cf. cannulation and cardiac puncture). Here, a general set of recommendations are provided for optimizing the blood sampling protocol that reflects best practices in animal welfare and sample integrity. This includes selecting appropriate use of anaesthetics for blood sampling as well as restraint techniques for situations where sedation is not used. In addition, ideal sampling environments where the fish can freely ventilate and strategies for minimizing handling time are discussed. This study summarizes the techniques used for extracting blood from the caudal vasculature in live fishes, highlighting the phlebotomy itself, the timing of sampling events and acceptable blood sample volumes. This study further discuss considerations for selecting appropriate physiological metrics when sampling in the caudal region and the potential benefits that this technique provides with respect to long-term biological assessments. Although general guidelines for blood sampling are provided here, it should be recognized that contextual considerations (e.g., taxonomic diversity, legal matters, environmental constraints) may influence the approach to blood sampling. Overall, it can be concluded that when done properly, blood sampling live fishes through the caudal vasculature is quick, efficient and minimally invasive, thus promoting conditions where live release of focal animals is possible.

A new tribe of braconid wasps provisionally included in the Rhyssalinae, Laibaleini trib. nov., type genus Laibalea gen. nov. (type species Laibalea enigmatica sp. nov.), from Kenya and the Central African Republic, is described. A molecular dataset, with emphasis on basally derived taxa based on four gene fragments (28S D2–D3 expansion region, COI barcode, elongation factor 1-alpha and 16S ribosomal DNA), was analysed both alone and in combination with a morphological dataset. Molecular phylogenetic placement of the new species into an existing subfamily is complicated by the extreme sequence divergence of the three sequences obtained for Laibalea. In both the combined sequence analysis and the combined DNA plus morphological tree, Laibalea is recovered as a sister group to the Rhyssalinae plus all non-cyclostome lineage braconids excluding Mesostoinae, Maxfischeriinae and Aphidiinae. A consensus of morphological characters and molecular analyses suggests inclusion of Laibalea either in the otherwise principally Holarctic subfamily Rhyssalinae or perhap more basally, in the principally Gondwanan Mesostoinae s.l., although we cannot exclude the possibility that it might represent a separate basal lineage. We place Laibalea in its own tribe, provisionally included in Rhyssalinae. The DNA sequence data are presented for several genera for the first time. Avga, the type genus of Avgini, is shown not to belong to Mesostoinae s.l. or Hormiinae, but its exact relationships remain uncertain. The generic compositions of Rhyssalinae and Mesostoinae s.l. are revised. Anachyra, Apoavga, Neptihormius, Neoavga and Opiopterus are shown to belong to Mesostoinae s.s. A key to the tribes of Rhyssalinae is provided.

OBJECTIVE Alterations of the gut microbiota have been implicated in many forms of arthritis, but an examination of cartilage microbial patterns has not been performed. This study was undertaken to characterize the microbial DNA profile of articular cartilage and determine changes associated with osteoarthritis (OA). METHODS We performed 16S ribosomal RNA gene deep sequencing on eroded and intact cartilage samples from knee OA patients (n = 21 eroded and 21 intact samples) and hip OA patients (n = 34 eroded and 33 intact samples) and cadaver controls (n = 10 knee samples and 10 hip samples). Microbial DNA diversity was assessed, groups were compared, and metagenomic profiles were reconstructed. Confirmation was performed in an independent cohort by clade-specific quantitative polymerase chain reaction. Findings in human cartilage were compared to those in cartilage from OA-susceptible C57BL/6 (B6) mice and OA-resistant MRL/MpJ (MRL) mice. Germ-free B6 mouse cartilage was analyzed as a methodologic control. RESULTS Alpha diversity was reduced in human OA versus control samples (P < 0.0001), and in hip versus knee samples (P < 0.0001). Numerous clades were different in human OA versus control samples, and similar findings were noted in comparisons of murine B6 versus MRL mice. Hip samples were microbiologically distinct from knee samples. OA microbial DNA demonstrated increased gram-negative constituents (P = 0.02). Functional analysis demonstrated increases in lipopolysaccharide production (P = 9.9 × 10-3 ), phosphatidylinositol signaling (P = 4.2 × 10-4 ), and nitrogen metabolism (P = 8 × 10-3 ) and decreases in sphingolipid metabolism (P = 7.7 × 10-4 ) associated with OA. CONCLUSION Our study reveals a microbial DNA signature in human and mouse cartilage. Alterations in this signature, including increases in gram-negative constituents, occur during the development and progression of human OA. Furthermore, our findings indicate that strain-specific signatures exist within mouse cartilage that mirror human patterns. Further study of the establishment and potential pathogenic role of these DNA signatures is needed.

The Trachypetidae is a newly recognised family of Ichneumonoidea endemic to Australia and one of the most distinctive wasp groups on the continent based on their large body size and superficial res...

Background Several mosquito collection methods are routinely used in vector control programmes. However, they target different behaviours causing bias in estimation of species diversity and abundance. Given the paucity of mosquito trap data in West Africa, we compared the performance of five trap-lure combinations and Human Landing Catches (HLCs) in Guinea. Methods CDC light traps (LT), BG sentinel 2 traps (BG2T), gravid traps (GT) and Stealth traps (ST) were compared in a 5 × 5 Latin Square design in three villages in Guinea between June and July 2018. The ST, a portable trap which performs similarly to a LT but incorporates LEDs and incandescent light, was included since it has not been widely tested. BG2T were used with BG and MB5 lures instead of CO2 to test the efficacy of these attractants. HLCs were performed for 5 nights, but not as part of the Latin Square. A Generalised Linear Mixed Model was applied to compare the effect of the traps, sites and collection times on mosquito abundance. Species identification was confirmed using PCR-based analysis and Sanger sequencing. Results A total of 10,610 mosquitoes were captured across five traps. ST collected significantly more mosquitoes (7096) than the rest of the traps, but resulted in a higher number of damaged specimens. ST and BG2T collected the highest numbers of Anopheles gambiae (s.l.) and Aedes aegypti mosquitoes, respectively. HLCs captured predominantly An. coluzzii (41%) and hybrids of An. gambiae and An. coluzzii (36%) in contrast to the five traps, which captured predominantly An. melas (83%). The rural site (Senguelen) presented the highest abundance of mosquitoes and overall diversity in comparison with Fandie (semi-rural) and Maferinyah Centre I (semi-urban). Our results confirm the presence of four species for the first time in Guinea. Conclusions ST collected the highest number of mosquitoes suggesting this trap may play an important role for mosquito surveillance in Guinea and similar sites in West Africa. We recommend the incorporation of molecular tools in entomological studies since they have helped to identify 25 mosquito species in this area.

Sex chromosomes vary greatly in their age and levels of differentiation across the tree of life. This variation is largely due to the rates of sex chromosome turnover in different lineages; however, we still lack an explanation for why sex chromosomes are so conserved in some lineages (e.g. mammals, birds) but so labile in others (e.g. teleosts, amphibians). To identify general mechanisms driving transitions in sex determination systems or forces which favour their conservation, we first require empirical data on sex chromosome systems from multiple lineages. Stickleback fishes are a valuable model lineage for the study of sex chromosome evolution due to variation in sex chromosome systems between closely-related species. Here, we identify the sex chromosome and a strong candidate for the master sex determination gene in the brook stickleback, Culaea inconstans. Using whole-genome sequencing of wild-caught samples and a lab cross, we identify AmhY, a male specific duplication of the gene Amh, as the candidate master sex determination gene. AmhY resides on Chromosome 20 in C. inconstans and is likely a recent duplication, as both AmhY and the sex-linked region of Chromosome 20 show little sequence divergence. Importantly, this duplicate AmhY represents the second independent duplication and recruitment of Amh as the sex determination gene in stickleback and the eighth example known across teleosts. We discuss this convergence in the context of sex chromosome turnovers and the role that the Amh/AmhrII pathway, which is crucial for sex determination, may play in the evolution of sex chromosomes in teleosts.

Wolbachia is a genus of obligate bacterial endosymbionts that infect a diverse range of arthropod species as well as filarial nematodes, with its single described species, Wolbachia pipientis, divided into several ‘supergroups’ based on multilocus sequence typing. Wolbachia strains in mosquitoes have been shown to inhibit the transmission of human pathogens including Plasmodium malaria parasites and arboviruses. Despite their large host range, Wolbachia strains within the major malaria vectors of the Anopheles (A.) gambiae and A. funestus complexes appear at low density based solely on PCR-based methods. Questions have been raised as to whether this represents a true endosymbiotic relationship. However, recent definitive evidence for two distinct, high-density strains of supergroup B Wolbachia within A. demeilloni and A. moucheti has opened exciting possibilities to explore naturally occurring Wolbachia endosymbionts in Anopheles for biocontrol strategies to block Plasmodium transmission. Here we utilise genomic analyses to demonstrate that both Wolbachia strains have retained all key metabolic and transport pathways despite their smaller genome size. We further confirm the presence of cytoplasmic incompatibility factor genes, despite noticeably few prophage regions. Additionally, phylogenetic analysis indicates that these Wolbachia strains may have been introduced into these two Anopheles species via horizontal transmission events, and unlikely to be by ancestral acquisition and subsequent loss events in the Anopheles gambiae species complex. These are the first Wolbachia genomes that enable us to study the relationship between natural strains Plasmodium malaria parasites and their Anopheline hosts.Impact statementWolbachia naturally infects a wide range of arthropod species, including insect vectors of human pathogens, where they may play a role in inhibiting their replication. These bacteria have been commonly found within Aedes (Ae.) albopictus and Culex pipiens mosquitoes but have been noticeably absent in the Anopheles mosquito genera, which includes all species responsible for malaria transmission. Recent PCR-based methods have suggested the potential for natural Wolbachia strains within the A. gambiae species complex, which includes major malaria vector species including A. gambiae s.s., A. coluzzii and A. arabiensis. We recently reported the presence of stable Wolbachia strains naturally occurring within two different Anopheles species (A. demeilloni and A. moucheti). In this study, we perform comparative genomic analysis of these two Wolbachia genomes against each other and published Wolbachia strains. The current assemblies are some of the smallest sequenced Wolbachia strains of insects, although their metabolic pathway repertoire is comparable to other strains. Interestingly, prophage fragments were identified within only one of the two strains. The findings of this study will be of significant interest to researchers investigating Wolbachia as a potential malaria biocontrol strategy, giving greater insight into the evolution and diversity of this obligate intracellular endosymbiont.Data summarySequence data generated and used for this analysis are available in the National Centre for Biotechnology Information Sequence Read Archive (NCBI SRA bioproject number PRJNA642000). The two assembled Wolbachia genomes are available with genome accession numbers GCA_018491735.2 and GCA_018491625.2. Additional Wolbachia genomes used for comparative analysis are described in the supplementary material.The authors confirm all supporting data, code and protocols have been provided within the article or through supplementary data files. Additional supplementary data files used to generate several figures can be found at: https://figshare.com/projects/Wolbachia_endosymbionts_in_two_Anopheles_species_indicates_independent_acquisitions_and_lack_of_prophage_elements/126533

Severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) infections were rising during early summer 2021 in many countries as a result of the Delta variant. We assessed reverse transcription polymerase chain reaction swab positivity in the Real-time Assessment of Community Transmission–1 (REACT-1) study in England. During June and July 2021, we observed sustained exponential growth with an average doubling time of 25 days, driven by complete replacement of the Alpha variant by Delta and by high prevalence at younger, less-vaccinated ages. Prevalence among unvaccinated people [1.21% (95% credible interval 1.03%, 1.41%)] was three times that among double-vaccinated people [0.40% (95% credible interval 0.34%, 0.48%)]. However, after adjusting for age and other variables, vaccine effectiveness for double-vaccinated people was estimated at between ~50% and ~60% during this period in England. Increased social mixing in the presence of Delta had the potential to generate sustained growth in infections, even at high levels of vaccination.

We identify amino acid variants within dominant SARS-CoV-2 T-cell epitopes by interrogating global sequence data. Several variants within nucleocapsid and ORF3a epitopes have arisen independently in multiple lineages and result in loss of recognition by epitope-specific T-cells assessed by IFN-γ and cytotoxic killing assays. Complete loss of T-cell responsiveness was seen due to Q213K in the A*01:01-restricted CD8+ ORF3a epitope FTSDYYQLY207-215, due to P13L, P13S and P13T in the B*27:05-restricted CD8+ nucleocapsid epitope QRNAPRITF9-17, and due to T362I and P365S in the A*03:01/A*11:01-restricted CD8+ nucleocapsid epitope KTFPPTEPK361-369. CD8+ T-cell lines unable to recognise variant epitopes have diverse T-cell receptor repertoires. These data demonstrate the potential for T-cell evasion and highlight the need for ongoing surveillance for variants capable of escaping T-cell as well as humoral immunity., Graphical Abstract

Streptococcus pneumoniae is a leading cause of pneumonia, meningitis, and bacteremia. Serotype 1 is rarely carried but is commonly associated with invasive pneumococcal disease, and in the African “meningitis belt,” it is prone to cause cyclical epidemics. We report the complete genome sequence of S. pneumoniae serotype 1 strain BVJ1JL, isolated in Malawi.

Opioid addiction (OA) has strong heritability, yet few genetic variant associations have been robustly identified. Only rs1799971, the A118G variant inOPRM1, has been identified as a genome-wide significant association with OA and independently replicated. We applied genomic structural equation modeling to conduct a GWAS of the new Genetics of Opioid Addiction Consortium (GENOA) data and published studies (Psychiatric Genomics Consortium, Million Veteran Program, and Partners Health), comprising 23,367 cases and effective sample size of 88,114 individuals of European ancestry. Genetic correlations among the various OA phenotypes were uniformly high (rg> 0.9). We observed the strongest evidence to date forOPRM1: lead SNP rs9478500 (p=2.56×10−9). Gene-based analyses identified novel genome-wide significant associations withPPP6CandFURIN. Variants within these loci appear to be pleiotropic for addiction and related traits.

International audience; Until recently, the field of sex chromosome evolution has been dominated by the canonical unidirectional scenario, first developed by Muller in 1918. This model postulates that sex chromosomes emerge from autosomes by acquiring a sex-determining locus. Recombination reduction then expands outwards from this locus, to maintain its linkage with sexually antagonistic/advantageous alleles, resulting in Y or W degeneration and potentially culminating in their disappearance. Based mostly on empirical vertebrate research, we challenge and expand each conceptual step of this canonical model and present observations by numerous experts in two parts of a theme issue of Phil. Trans. R. Soc. B. We suggest that greater theoretical and empirical insights into the events at the origins of sex-determining genes (rewiring of the gonadal differentiation networks), and a better understanding of the evolutionary forces responsible for recombination suppression are required. Among others, crucial questions are: Why do sex chromosome differentiation rates and the evolution of gene dose regulatory mechanisms between male versus female heterogametic systems not follow earlier theory? Why do several lineages not have sex chromosomes? And: What are the consequences of the presence of (differentiated) sex chromosomes for individual fitness, evolvability, hybridization and diversification? We conclude that the classical scenario appears too reductionistic. Instead of being unidirectional, we show that sex chromosome evolution is more complex than previously anticipated and principally forms networks, interconnected to potentially endless outcomes with restarts, deletions and additions of new genomic material. This article is part of the theme issue ‘Challenging the paradigm in sex chromosome evolution: empirical and theoretical insights with a focus on vertebrates (Part II)’.

While ATM loss-of-function has long been identified as the genetic cause of Ataxia Telangiectasia (AT), how this genetic mutation leads to selective and progressive cerebellar degeneration of Purkinje and granule cells remains unknown. We performed single-nucleus RNA-sequencing of the human cerebellum and prefrontal cortex from individuals with AT and matched unaffected controls to identify AT-associated transcriptomic changes in a cell-type- and brain-region-specific manner. We provide the largest single-nucleus transcriptomic atlas of the adult human cerebellum to-date (126,356 nuclei), identify upregulation of apoptotic and ER stress pathways in Purkinje and granule neurons, and uncover strong downregulation of calcium ion homeostasis genes in Purkinje neurons. Our analysis reveals prominent inflammation of microglia in AT cerebellum with transcriptional signatures similar to aging and neurodegenerative microglia, and suggests that microglia activation precedes Purkinje and granule neuron death in disease progression. Our data implicates a novel role of microglial activation underlying cerebellar degeneration in AT.

The loss of recombination between sex chromosomes has occurred repeatedly throughout nature, with important implications for their subsequent evolution. Explanations for this remarkable convergence have generally invoked only adaptive processes (e.g. sexually antagonistic selection); however, there is still little evidence for these hypotheses. Here we propose a model in which recombination on sex chromosomes is lost due to the neutral accumulation of sequence divergence adjacent to (and thus, in linkage disequilibrium with) the sex determiner. Importantly, we include in our model the fact that sequence divergence, in any form, reduces the probability of recombination between any two sequences. Using simulations, we show that, under certain conditions, a region of suppressed recombination arises and expands outwards from the sex-determining locus, under purely neutral processes. Further, we show that the rate and pattern of recombination loss are sensitive to the pre-existing recombination landscape of the genome and to sex differences in recombination rates, with patterns consistent with evolutionary strata emerging under some conditions. We discuss the applicability of these results to natural systems. This article is part of the theme issue ‘Challenging the paradigm in sex chromosome evolution: empirical and theoretical insights with a focus on vertebrates (Part I)’.

Multiple stressors are commonly encountered by wild animals, but their cumulative effects are poorly understood, especially regarding infection development. We conducted a holding study with repeated gill and blood sampling to characterize the effects of cumulative stressors on infection development in adult coho salmon. Treatments included chronic thermal stress (15°C vs. 10°C) and acute gill net entanglement with an air exposure (simulating fisheries bycatch release). The potential loadings of 35 infectious agents and the expression of 17 host immune genes were quantified using high-throughput quantitative polymerase chain reaction, while host physiology was characterized with chemical analysis of blood. Temporal increases in infectious agent richness and loads were concurrent with decreased expression of immune genes in fish sampled in the river. In the laboratory, mortality was minimal in cool water regardless of fishery treatment ( 1 wk) and enhanced mortality associated with handling and biopsy (∼40% both sexes). Experimental gillnetting at high temperature further enhanced female mortality (73%). Fish held at high temperature demonstrated heavier infectious agent loads, osmoregulatory impairment, suppressed female maturation, and upregulation of inflammatory and extracellular immune genes. At high temperature, heavy Parvicapsula minibicornis loads were associated with premature mortality. Females exhibited physiological impairment from both stressors after 1 wk, and infection burdens correlated poorly with immune gene regulation compared with males. Cumulative effects of multiple stressors on female mortality are likely a function of physiological impairment and enhanced infections at high temperature.

Microbiomes are vast communities of microorganisms and viruses that populate all natural ecosystems. Viruses have been considered to be the most variable component of microbiomes, as supported by virome surveys and examples of high genomic mosaicism. However, recent evidence suggests that the human gut virome is remarkably stable compared with that of other environments. Here, we investigate the origin, evolution and epidemiology of crAssphage, a widespread human gut virus. Through a global collaboration, we obtained DNA sequences of crAssphage from more than one-third of the world's countries and showed that the phylogeography of crAssphage is locally clustered within countries, cities and individuals. We also found fully colinear crAssphage-like genomes in both Old-World and New-World primates, suggesting that the association of crAssphage with primates may be millions of years old. Finally, by exploiting a large cohort of more than 1,000 individuals, we tested whether crAssphage is associated with bacterial taxonomic groups of the gut microbiome, diverse human health parameters and a wide range of dietary factors. We identified strong correlations with different clades of bacteria that are related to Bacteroidetes and weak associations with several diet categories, but no significant association with health or disease. We conclude that crAssphage is a benign cosmopolitan virus that may have coevolved with the human lineage and is an integral part of the normal human gut virome. ispartof: NATURE MICROBIOLOGY vol:4 issue:10 pages:1727-1736 ispartof: location:England status: published

In estuary and coastal systems, human demand for freshwater, climate change‐driven precipitation variability, and extreme weather impact salinity levels, reducing connectivity between mesohaline coastal fish populations and potentially contributing to genomic divergence. We examined gill transcriptome responses to salinity in wild‐caught juveniles from two populations of Sacramento splittail (Pogonichthys macrolepidotus), a species of conservation concern that is endemic to the San Francisco Estuary, USA, and the lower reaches of its tributaries. Recent extreme droughts have led to salinities above the tolerance limits for this species, creating a migration barrier between these populations, which potentially contributed to population divergence. We identified transcripts involved in a conserved response to salinity; however, the more salinity‐tolerant San Pablo population had greater transcriptome plasticity (3.6‐fold more transcripts responded than the Central Valley population) and a response consistent with gill remodeling after 168 hr of exposure to elevated salinity. The reorganization of the gill in response to changing osmotic gradients is a process critical for acclimation and would facilitate enhanced salinity tolerance. We detected an upregulation of receptors that control the Wnt (wingless‐type) cell signaling pathway that may be required for an adaptive response to increases in salinity, patterns not observed in the relatively salinity‐sensitive Central Valley population. We detected 62 single nucleotide polymorphisms (SNPs) in coding regions of 26 transcripts that differed between the populations. Eight transcripts that contained SNPs were associated with immune responses, highlighting the importance of diversity in immune gene sequences as a defining characteristic of genomic divergence between these populations. Our data demonstrate that these populations have divergent transcriptomic responses to salinity, which is consistent with observed physiological differences in salinity tolerance.

Summary Objective This review was designed to identify highlights of the osteoarthritis (OA) genetics and epigenetics literature published between April 2017 and January 2018. Design A Pubmed literature search was conducted using the keywords ‘osteoarthritis’ and each of the following: ‘genomic’, ‘genetic’, ‘epigenomic’, ‘epigenetic’, ‘histone’, ‘noncoding RNA’, ‘miRNA’, ‘lncRNA’, ‘DNA methylation’, ‘DNA hydroxymethylation’, ‘DNMT’, and ‘TET’. The dates of publication were restricted to 4/1/2017–1/15/2018. Results were compared to the same search terms limited to 4/1/2016–1/15/2017. Results Virtually all search term combinations demonstrated a decrease in papers published this year compared to last, with epigenetic and miRNA/lncRNA research being stable. Despite this, numerous advances were made this year, including the second large genome-wide association study (GWAS) study of hand OA, a new twin study of hip and knee OA concordance, an extensive study of GDF5 evolution, analyses of the contribution of Dnmt3a to OA, a description of DNA methylation in a nonhuman primate model of OA, and an integrated, multi-omics analysis of DNA methylation, mRNA, and protein expression in human OA samples, among others. A variety of micro- and a few circular-RNA studies were also published, highlighting the importance of noncoding RNA in both the pathogenesis and potential treatment of OA. Conclusion Although publications have decreased slightly in the last year, genetics and epigenetics continue to be a topic of substantial research in OA, and considerable progress continues to be made in the field.