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Marine bivalve mollusc shells can offer valuable insights into past oceanographic variability and seasonality. Given its ecological and archaeological significance, Mytilus californianus (California mussel) presents the opportunity to examine seasonal and decadal changes recorded in its shell over centuries to millennia. While dark–light growth bands in M. californianus shells could be advantageous for reconstructing past environments, uncertainties remain regarding shell structure, environmental controls of dark–light band formation, and the amount of time represented by a dark–light pair. By analyzing a suite of M. californianus shells collected in 2002, 2003, 2019, and 2020 from Bodega Bay, California, we describe the mineralogical composition, establish relationships among growth band pattern, micro-environment, and collection season, and compare shell structure and growth band expression between the archival (2002–2003) and modern (2019–2020) shells. We identified three mineralogical layers in M. californianus: an outer prismatic calcite layer, a middle aragonite layer, and a secondary inner prismatic calcite layer, which makes M. californianus the only Mytilus species to precipitate a secondary calcite layer. Within the inner calcite layer, light bands are strongly correlated with winter collection months and could be used to reconstruct periods with moderate, stable temperatures and minimal upwelling. Additionally, modern shells have significantly thinner inner calcite layers and more poorly expressed growth bands than the archival shells, although we also show that growth band contrast is strongly influenced by micro–environment. Mytilus californianus from northern California is calcifying differently, and apparently more slowly, than it was 20 years ago.

Microbes interact in natural communities in a spatially structured manner, particularly in biofilms and polymicrobial infections. While next generation sequencing approaches provide powerful insights into diversity, metabolic capacity, and mutational profiles of these communities, they generally fail to recover in situ spatial proximity between distinct genotypes in the interactome. Hi-C is a promising method that has assisted in analysing complex microbiomes, by creating chromatin cross-links in cells, that aid in identifying adjacent DNA, to improve de novo assembly. This study explored a modified Hi-C approach involving an initial lysis phase prior to DNA cross-linking, to test whether adjacent cell chromatin can be cross-linked, anticipating that this could provide a new avenue for study of spatial-mutational dynamics in structured microbial communities. An artificial polymicrobial mixture of Pseudomonas aeruginosa, Staphylococcus aureus, and Escherichia coli was lysed for 1-18 h, then prepared for Hi-C. A murine biofilm infection model was treated with sonication, mechanical lysis, or chemical lysis before Hi-C. Bioinformatic analyses of resulting Hi-C interspecies chromatin links showed that while microbial species differed from one another, generally lysis significantly increased links between species and increased the distance of Hi-C links within species, while also increasing novel plasmid-chromosome links. The success of this modified lysis-Hi-C protocol in creating extracellular DNA links is a promising first step toward a new lysis-Hi-C based method to recover genotypic microgeography in polymicrobial communities, with potential future applications in diseases with localized resistance, such as cystic fibrosis lung infections and chronic diabetic ulcers.

Salt marshes and seagrass meadows can sequester and store high quantities of organic carbon (OC) in their sediments relative to other marine and terrestrial habitats. Assessing carbon stocks, carbon sources, and the transfer of carbon between habitats within coastal seascapes are each integral in identifying the role of blue carbon habitats in coastal carbon cycling. Here, we quantified carbon stocks, sources, and exchanges in seagrass meadows, salt marshes, and unvegetated sediments in six bays along the California coast. In the top 20 cm of sediment, the salt marshes contained approximately twice as much OC as seagrass meadows did, 4.92 ± 0.36 kg OC m−2 compared to 2.20 ± 0.24 kg OC m−2, respectively. Both salt marsh and seagrass sediment carbon stocks were higher than previous estimates from this region but lower than global and US-wide averages, respectively. Seagrass-derived carbon was deposited annually into adjacent marshes during fall seagrass senescence. However, isotope mixing models estimate that negligible amounts of this seagrass material were ultimately buried in underlying sediment. Rather, the vast majority of OC in sediment across sites was likely derived from planktonic/benthic diatoms and/or C3 salt marsh plants.

Belugas (Delphinapterus leucas) in managed care have been reported to show seasonal variation in socio-sexual behaviour, hormone levels and respiration rates; however, little is known about the social interactions of wild belugas when they are not in summer, near-shore congregations. To better understand if belugas show seasonal variation in social interactions, this study recorded the behaviour of 10 belugas (five females, five males, ranging from birth to 10 years of age) housed in managed care. Social interactions typically peaked in the summer months but persisted at very low levels during the rest of the year. Seasonal variation was most dramatic for socio-sexual behaviour but was generally mirrored in pattern by agonistic and affiliative interactions. Subjects closer to maturity displayed more seasonal variation than younger subjects, and males displayed more seasonal variation compared to females. The peak in social interactions found in this study aligns rather closely with wild belugas’ summer, near-shore congregations, where belugas have increased opportunities for socializing. Although belugas in managed care do not experience a seasonal change in habitat, they do show seasonal changes in social behaviour, which are likely driven by seasonal fluctuations in hormone levels. It is therefore expected that wild beluga populations would show similar behavioural patterns if they were observed throughout the remainder of the year. This research has applications for belugas in managed care and may provide a framework for understanding the social behaviour of wild belugas.

Behavioural observations of captive beluga whales have complemented and extended much of what has been learnt about this species in the wild. Aquarium-based research has provided finer-scale specificity for many topics, including the seasonal breeding pattern that is characteristic of this species, as well as socio-sexual behaviour that appears to be an important part of the behavioural repertoire of this species. One example is a strong propensity for male–male social interactions that begin to develop at an early age. In addition, detailed behavioural milestones in calves have been documented in ways that extend that which have been collected from wild populations. These include swim positions with mother, separations/reunions with mother, and other social interactions, and play. Characteristics of beluga maternal care have also been studied more often in captive settings than in the wild, particularly with respect to details pertaining to nursing behaviour, individual differences in maternal style and allomaternal care. Other topics that have received scientific scrutiny in zoological settings include individual differences and behavioural laterality. Thus, a greater understanding of beluga behavioural biology has the potential to emerge as a consequence of synergy between research conducted in the two settings.

Butterflies and moths (Lepidoptera) are one of the most studied, diverse, and widespread animal groups, making them an ideal model for climate change research. They are a particularly informative model for studying the effects of climate change on species ecology because they are ectotherms that thermoregulate with a suite of physiological, behavioural, and phenotypic traits. While some species have been negatively impacted by climatic disturbances, others have prospered, largely in accordance with their diversity in life‐history traits. Here we take advantage of a large repertoire of studies on butterflies and moths to provide a review of the many ways in which climate change is impacting insects, animals, and ecosystems. By studying these climate‐based impacts on ecological processes of Lepidoptera, we propose appropriate strategies for species conservation and habitat management broadly across animals.

Quantifying the strength of non-trophic interactions exerted by foundation species is critical to understanding how natural communities respond to environmental stress. In the case of ocean acidification (OA), submerged marine macrophytes, such as seagrasses, may create local areas of elevated pH due to their capacity to sequester dissolved inorganic carbon through photosynthesis. However, although seagrasses may increase seawater pH during the day, they can also decrease pH at night due to respiration. Therefore, it remains unclear how consequences of such diel fluctuations may unfold for organisms vulnerable to OA. We established mesocosms containing different levels of seagrass biomass (Zostera marina) to create a gradient of carbonate chemistry conditions and explored consequences for growth of juvenile and adult oysters (Crassostrea gigas), a non-native species widely used in aquaculture that can co-occur, and is often grown, in proximity to seagrass beds. In particular, we investigated whether increased diel fluctuations in pH due to seagrass metabolism affected oyster growth. Seagrasses increased daytime pH up to 0.4 units but had little effect on nighttime pH (reductions less than 0.02 units). Thus, both the average pH and the amplitude of diel pH fluctuations increased with greater seagrass biomass. The highest seagrass biomass increased oyster shell growth rate (mm day−1) up to 40%. Oyster somatic tissue weight and oyster condition index exhibited a different pattern, peaking at intermediate levels of seagrass biomass. This work demonstrates the ability of seagrasses to facilitate oyster calcification and illustrates how non-trophic metabolic interactions can modulate effects of environmental change.

Intra-specific aggression is not frequently observed in wild cetaceans, including belugas. One proxy, identified in past research, that indicates past aggressive behaviour is the presence of rake marks (scars left on skin by the teeth of conspecifics). Behavioural observations of belugas, compared to bottlenose dolphins, suggest that belugas engage in less physically aggressive behaviour; yet, a detailed study of beluga aggressive behaviour remains to be conducted. Beluga intra-specific aggression was assessed by scoring photographs taken from July to August in 2015 at Cunningham Inlet, Canada for the presence/absence and body location of rake marks. Of the 252 belugas analysed, 44% had rake marks. The results suggest that physical aggression occurs comparatively less with only half of the observed beluga population having rake marks compared to almost all bottlenose dolphins previously surveyed. We suggest social structure, skin pigmentation, and/or species-specific behaviours as explanations for the differences in rake marks among species.

Isolation of ovarian follicles is a key step in culture systems for large mammalian species to promote the continued growth of follicles beyond the preantral stage in fertility preservation efforts. Still, mechanical isolation methods are user-skill dependent and time-consuming, whereas enzymatic strategies carry increased risk of damaging theca cell layers and the basement membranes. Here, we sought to determine an optimal method to rescue domestic cat (Felis catus) early antral and antral stage follicles from ovarian tissue and to evaluate the influence of isolation strategy on follicle development, survival, and gene expression during 14 days of in vitro culture in alginate hydrogel. Mechanical isolation was compared with 90 min digestion in 0.7 and 1.4 Wünsch units/mL Liberase blendzyme (0.7L and 1.4L, respectively). Mechanical isolation resulted in improved follicle growth and survival, and better antral cavity and theca cell maintenance in vitro, compared with 1.4L (P < 0.05) but displayed higher levels of apoptosis after incubation compared with enzymatically isolated follicles. However, differences in follicle growth and survival were not apparent until 7+ days in vitro. Expressions of CYP19A1, GDF9, LHR, or VEGFA were similar among isolation-strategies. Cultured follicles from all isolation methods displayed reduced STAR expression compared with freshly isolated follicles obtained mechanically or via 0.7L, suggesting that prolonged culture resulted in loss of theca cell presence and/or function. In sum, early antral and antral stage follicle development in vitro is significantly influenced by isolation strategy but not necessarily observable in the absence of extended culture. These results indicate that additional care must be taken in follicle isolation optimizations for genome rescue and fertility preservation efforts., Lay summary The ovary contains hundreds of eggs with only a select few developing from an immature stage through to ovulation over the course of an animal’s lifetime. Rescue of eggs from this pool, and the ability to grow them in culture to a mature stage, would be incredibly valuable for fertility preservation efforts in both humans and endangered species. Currently, the isolation of ovarian follicles (eggs with their surrounding helper cells) is a key step in culture systems for large mammalian species, to promote continued growth. Yet, isolation methods may affect the follicle’s future developmental capacity. We evaluated two isolation strategies, mechanical micro-dissection (needle/scalpel blade) and enzymatic digestion (using Liberase blendzyme) on ovaries of domestic cats obtained via routine spay procedures. Mechanically isolated follicles displayed improved growth, survival, and indications of developmental competence in 14-day culture, compared with high concentration (1.4 Wünsch units/mL) enzyme-isolated follicles. However, mechanical isolation was not different from low (0.7 Wünsch units/mL) enzyme for these metrics, or for expression of key genes indicative of follicular cell functions. Further, differences in follicle growth/survival were not apparent until 7+ days in culture. Thus, ovarian follicle isolation strategies influence developmental potential in culture, and extended culture will be required to identify optimal methods for fertility preservation efforts., Graphical Abstract Created in BioRender.com

Global‐scale ocean acidification has spurred interest in the capacity of seagrass ecosystems to increase seawater pH within crucial shoreline habitats through photosynthetic activity. However, the dynamic variability of the coastal carbonate system has impeded generalization into whether seagrass aerobic metabolism ameliorates low pH on physiologically and ecologically relevant timescales. Here we present results of the most extensive study to date of pH modulation by seagrasses, spanning seven meadows (Zostera marina) and 1000 km of U.S. west coast over 6 years. Amelioration by seagrass ecosystems compared to non‐vegetated areas occurred 65% of the time (mean increase 0.07 ± 0.008 SE). Events of continuous elevation in pH within seagrass ecosystems, indicating amelioration of low pH, were longer and of greater magnitude than opposing cases of reduced pH or exacerbation. Sustained elevations in pH of >0.1, comparable to a 30% decrease in [H+], were not restricted only to daylight hours but instead persisted for up to 21 days. Maximal pH elevations occurred in spring and summer during the seagrass growth season, with a tendency for stronger effects in higher latitude meadows. These results indicate that seagrass meadows can locally alleviate low pH conditions for extended periods of time with important implications for the conservation and management of coastal ecosystems., The most extensive study to date of pH modulation by seagrasses, spanning seven meadows (Zostera marina) and 1000 km of U.S. west coast over 6 years. Amelioration of low pH by seagrass ecosystems occurred most of the time, where events of continuous elevation in pH were longer and of greater magnitude than opposing cases of reduced pH or exacerbation. Sustained elevations in pH were not restricted only to daylight hours. Maximal pH elevations occurred in spring and summer during the seagrass growth season, with a tendency for stronger effects in higher latitude meadows.

Heart failure with preserved ejection fraction (HFpEF) is now the dominant form of heart failure and one for which no efficacious therapies exist. Obesity and lipid mishandling greatly contribute to HFpEF. However, molecular mechanism(s) governing metabolic alterations and perturbations in lipid homeostasis in HFpEF are largely unknown. Here, we report that cardiomyocyte steatosis in HFpEF is coupled with increases in the activity of the transcription factor FoxO1 (Forkhead box protein O1). FoxO1 depletion, as well as over-expression of the Xbp1s (spliced form of the X-box-binding protein 1) arm of the UPR (unfolded protein response) in cardiomyocytes each ameliorates the HFpEF phenotype in mice and reduces myocardial lipid accumulation. Mechanistically, forced expression of Xbp1s in cardiomyocytes triggers ubiquitination and proteasomal degradation of FoxO1 which occurs, in large part, through activation of the E3 ubiquitin ligase STUB1 (STIP1 homology and U-box-containing protein 1) a novel and direct transcriptional target of Xbp1s. Our findings uncover the Xbp1s-FoxO1 axis as a pivotal mechanism in the pathogenesis of cardiometabolic HFpEF and unveil previously unrecognized mechanisms whereby the UPR governs metabolic alterations in cardiomyocytes., Heart failure with preserved ejection fraction (HFpEF) is a global, major health issue for which no effective therapies are available. Here, the authors discover that the interplay between two transcription factors, Xbp1s and FoxO1, is critical for metabolic adaptation and lipid handling in HFpEF-stressed cardiomyocytes.

The hydrolytic deamination of adenosine-to-inosine (A-to-I) by RNA editing is a widespread post-transcriptional modification catalyzed by the adenosine deaminase acting on RNA (ADAR) family of proteins. ADAR-mediated RNA editing modulates cellular pathways involved in innate immunity, RNA splicing, RNA interference, and protein recoding, and has been investigated as a strategy for therapeutic intervention of genetic disorders. Despite advances in basic and translational research, the mechanisms regulating RNA editing are poorly understood. Though several trans-acting regulators of editing have been shown to modulate ADAR protein expression, previous studies have not identified factors that modulate ADAR catalytic activity. Here, we show that RNA editing increases upon intracellular acidification, and that these effects are predominantly explained by both enhanced ADAR base-flipping and deamination rate at acidic pH. We also show that the extent of RNA editing increases with the reduction in pH associated with conditions of cellular hypoxia., Graphical Abstract Graphical AbstractIntracellular acidification drives protonation of a conserved glutamate in the ADAR deaminase domain, which in turn enhances base-flipping and increases the extent of RNA editing.

Conservation management is improved by incorporating information about the spatial distribution of population genetic diversity into planning strategies. Northern Australia is the location of some of the world’s most severe ongoing declines of endemic mammal species, yet we have little genetic information from this regional mammal assemblage to inform a genetic perspective on conservation assessment and planning. We used next-generation sequencing data from remnant populations of the threatened brush-tailed rabbit-rat (Conilurus penicillatus) to compare patterns of genomic diversity and differentiation across the landscape and investigate standardised hierarchical genomic diversity metrics to better understand brush-tailed rabbit-rat population genomic structure. We found strong population structuring, with high levels of differentiation between populations (FST = 0.21–0.78). Two distinct genomic lineages between the Tiwi Islands and mainland are also present. Prioritisation analysis showed that one population in both lineages would need to be conserved to retain at least ~80% of alleles for the species. Analysis of standardised genomic diversity metrics showed that approximately half of the total diversity occurs among lineages (δ = 0.091 from grand total γ = 0.184). We suggest that a focus on conserving remnant island populations may not be appropriate for the preservation of species-level genomic diversity and adaptive potential, as these populations represent a small component of the total diversity and a narrow subset of the environmental conditions in which the species occurs. We also highlight the importance of considering both genomic and ecological differentiation between source and receiving populations when considering translocations for conservation purposes.

Adult bottlenose dolphins share pectoral fin contacts (PFC) to manage their social relationships but less is known about how mothers share PFC with their calves. Using a dataset collected over 16 years, we analyzed how 10 matrilines, including three second generation female dolphins in a maternal role, used PFC with their pre-weaned calves. Mothers had different rates of initiation with their calves forming a continuum from those initiating few contacts (15%) to those initiating more (44%). For mothers with all-aged calves, the lateral side was contacted the most to start interactions with mothers contacting body parts at a similar rate. All mothers assumed the same posture regardless of their role as initiator or receiver, with horizontal the most prevalent posture. Two maternal styles were found for PFC: high and low use of PFC. Within the high PFC group, there was individual variation that was related to calf sex. Even though evidence of maternal style was confirmed in PFC exchanges between adult female dolphins and their calves, the number of PFC shared between these kin was only ~9% of all documented PFC contacts (N = 4,345) over 16 years, suggesting that other forms of tactile contact may be more important within the confines of the mother-offspring relationship in delphinids.

Background Dietary sulfur amino acid restriction (SAAR) improves body composition and metabolic health across several model organisms in part through induction of the integrated stress response (ISR). Objective We investigate the hypothesis that activating transcription factor 4 (ATF4) acts as a converging point in the ISR during SAAR. Methods Using liver-specific or global gene ablation strategies, in both female and male mice, we address the role of ATF4 during dietary SAAR. Results We show that ATF4 is dispensable in the chronic induction of the hepatokine fibroblast growth factor 21 while being essential for the sustained production of endogenous hydrogen sulfide. We also affirm that biological sex, independent of ATF4 status, is a determinant of the response to dietary SAAR. Conclusions Our results suggest that auxiliary components of the ISR, which are independent of ATF4, are critical for SAAR-mediated improvements in metabolic health in mice.

Hamilcar and Hannibal Barca embody a colossal father-son military legacy. Yet their family – the so-called ‘Barcid’ dynasty – has a murky history. Modern scholars have presumed that Hamilcar, the first notable historical figure to bear the name Barkas, received it as a ‘nickname’ meaning ‘lightning’. The rationale is that the name derives from the Phoenician word brq and is thus the equivalent to the Greek epithet Keraunos. There is, however, no evidence in our classical sources, to which exclusively we owe our knowledge of events, supporting this. Furthermore, the name Barca was passed on to Hamilcar’s sons, something suggestive of an inherited family surname. This article submits an alternative to the widely endorsed ‘lightning’ theory. This new perspective explores the possibility that the Barcid dynasty had roots in the city of Barce in Cyrenaica and was a relatively new addition to the Carthaginian aristocracy in the third century BC. Using textual evidence from Polybius, Diodorus and others, this fresh take clarifies other aspects of the Barcid dynasty’s tumultuous history, such as their animosity towards the Carthaginian Council of Elders and their departure to Spain in the 220s.

Significance The pH of the global ocean is decreasing due to the absorption of anthropogenically emitted CO2, causing ocean acidification (OA). OA negatively impacts marine shellfish and threatens the continuing economic viability of molluscan shellfish aquaculture, a global industry valued at more than 19 billion USD. We identify traits linked to growth and lipid regulation that contribute tolerance to OA in abalone aquaculture, with broader implications for adaptation efforts in other shellfish species. We also identify evolved heritable variation for physiological resilience to OA that may be exploited in commercial and restoration aquaculture breeding programs to offset the negative consequences of continuing climate change., Ocean acidification (OA) poses a major threat to marine ecosystems and shellfish aquaculture. A promising mitigation strategy is the identification and breeding of shellfish varieties exhibiting resilience to acidification stress. We experimentally compared the effects of OA on two populations of red abalone (Haliotis rufescens), a marine mollusc important to fisheries and global aquaculture. Results from our experiments simulating captive aquaculture conditions demonstrated that abalone sourced from a strong upwelling region were tolerant of ongoing OA, whereas a captive-raised population sourced from a region of weaker upwelling exhibited significant mortality and vulnerability to OA. This difference was linked to population-specific variation in the maternal provisioning of lipids to offspring, with a positive correlation between lipid concentrations and survival under OA. This relationship also persisted in experiments on second-generation animals, and larval lipid consumption rates varied among paternal crosses, which is consistent with the presence of genetic variation for physiological traits relevant for OA survival. Across experimental trials, growth rates differed among family lineages, and the highest mortality under OA occurred in the fastest growing crosses. Identifying traits that convey resilience to OA is critical to the continued success of abalone and other shellfish production, and these mitigation efforts should be incorporated into breeding programs for commercial and restoration aquaculture.

For endangered sea turtle populations, microbial pathogens of developing embryos are of concern at nesting sites around the globe. For olive ridley turtles, hatching success is markedly lower at mass-nesting sites than at solitary nesting beaches, a case presumably resulting from the abundance of decomposing eggs generated by nesting turtles destroying adjacent eggs. This organic input drives microbial activity, affecting the nest environment (i.e. pO2and temperature), and reducing embryo survivorship and hatching success. However, the composition of microbial communities in nest sand has not been studied in detail and the presence of potential pathogens can, therefore, not be discounted. As a part of a larger study that investigated microbial abundance in nests, we employed high-throughput DNA sequencing to compare fungal and bacterial composition in nest sand from areas of disparate embryo survivorship. While we found no differences in alpha-diversity (mean operational taxonomic unit diversity within each site) among nesting areas, the microbial community composition of each area was distinct, and differences in community structure corresponded with variable hatching success. Some sequences of potential sea turtle egg pathogens were obtained (e.g.Fusarium solanispecies complex), but were in low relative abundance, and their presence was not associated with low hatching success. Our results from the arribada beach at Ostional, Costa Rica, provide further evidence that the physical characteristics of the nest (including those that determine microbial composition and activity) are likely more relevant to hatching success than the presence of potential pathogens or microbial community structure alone.

Acetylation of α-tubulin at conserved lysine 40 (K40) amino acid residue regulates microtubule dynamics and controls a wide range of cellular activities. Dysregulated microtubule dynamics characterized by differential α-tubulin acetylation is a hallmark of cancer, neurodegeneration, and other complex disorders. Hence, accurate quantitation of α-tubulin acetylation is required in human disease and animal model studies. We developed a novel antibody-free proteomics assay to measure α-tubulin acetylation targeting protease AspN-generated peptides harboring K40 site. Using the synthetic unmodified and acetylated stable isotope labeled peptides DKTIGGG and DKTIGGGD, we demonstrate assay linearity across 4 log magnitude and reproducibility of

Benthic microalgae play important roles in energy flow and biogeochemistry of coastal ecosystems; however, factors influencing community composition remain largely unknown. Our purpose was to identify and compare spatial and environmental influences on benthic diatom biogeography at regional scales. In summer 2018, we sampled sediment at various spatial scales (0.0001–180 km) from five saltmarshes in South Carolina, USA, and characterized diatom assemblages using DNA metabarcoding. Twenty-three environmental variables from marsh sediments, adjacent creeks, and atmosphere were recorded. Multivariate analyses revealed that the saltmarsh communities were clearly distinct. Community dissimilarity was compared to both geographic distance and environmental differences to determine influences on community structure. Mantel tests and redundancy analysis revealed that spatial influences, in addition to several environmental factors (phosphate, grain size, sediment sorting, sediment moisture, and creek salinity), were significant. Variation partitioning revealed that 26% of community variation was explained by geographic distance alone, whereas 60% could be explained by combined spatial/environmental factors. In contrast, the independent explanatory power of individual environmental factors was negligible. Our findings suggest that spatially structured environmental variation mainly conditioned the saltmarsh diatom biogeography in this region. Dispersal limitation, as evinced by the large pure spatial effect and distance-decay pattern, was also important. Spatial effects were stronger relative to that previously observed in other microbial groups (marine bacteria and phytoplankton) and detected at finer spatial scales. Results support prior studies that suggest body size and dispersal mode are important drivers of metacommunity structure and therefore must be considered when studying aquatic microbial biogeography.

Salt marshes face chronic anthropogenic impacts such as relative sea level rise and eutrophication, as well as acute disturbances from tropical storms that can affect the productivity of these important communities. However, it is not well understood how marshes already subjected to eutrophication and sea level rise will respond to added effects of episodic storms such as hurricanes. We examined the interactive effects of nutrient addition, sea level rise, and a hurricane on the growth, biomass accumulation, and resilience of the saltmarsh cordgrass Spartina alterniflora in the Gulf of Mexico. In a microtidal marsh, we manipulated nutrient levels and submergence using marsh organs in which cordgrasses were planted at differing intertidal elevations and measured the impacts of Hurricane Isaac, which occurred during the experiment. Prior to the hurricane, grasses at intermediate and high elevations increased in abundance. After the hurricane, all treatments lost approximately 50% of their shoots, demonstrating that added nutrients and elevation did not provide resistance to hurricane disturbance. At the end of the experiment, only the highest elevations had been resilient to the hurricane, with increased above- and belowground growth. Added nutrients provided a modest increase in above- and belowground growth, but only at the highest elevations, suggesting that only elevation will enhance resilience to hurricane disturbance. These results empirically demonstrate that S. alterniflora in microtidal locations already subjected to submergence stress is less able to recover from storm disturbance and suggests we may be underestimating the loss of northern Gulf Coast marshes due to relative sea level rise.

A range of bacteria and archaea produce gas vesicles as a means to facilitate flotation. These gas vesicles have been purified from a number of species and their applications in biotechnology and medicine are reviewed here. Halobacterium sp. NRC-1 gas vesicles have been engineered to display antigens from eukaryotic, bacterial and viral pathogens. The ability of these recombinant nanoparticles to generate an immune response has been quantified both in vitro and in vivo. These gas vesicles, along with those purified from Anabaena flos-aquae and Bacillus megaterium , have been developed as an acoustic reporter system. This system utilizes the ability of gas vesicles to retain gas within a stable, rigid structure to produce contrast upon exposure to ultrasound. The susceptibility of gas vesicles to collapse when exposed to excess pressure has also been proposed as a biocontrol mechanism to disperse cyanobacterial blooms, providing an environmental function for these structures.

The retinoic acid-related orphan receptors alpha (RORa) are members of the steroid/thyroid nuclear receptor super-family and core components of the circadian timing system. In the present study, we continue to investigate the role of RORas in human breast cancer. Assays using the RORa response element (RORE)-tk-luciferase reporter demonstrate the functionality of the RORa1 in MCF-7 breast cancer cells and that over-expression of RORa1 stimulates MCF-7 human breast cancer cell proliferation. Genomic analysis revealed that RORα1 over-expression regulated the transcription of numerous genes in MCF-7 breast cancer cells including increasing the expression of connexin 43 (CX43), aldo-keto reductases 1C1 (AKR1C1), and AKR1C3. Furthermore, administration of the pineal hormone melatonin represses RORa1 induction of CX43, AKR1C1, and AKR1C3 in MCF-7 cells. AKR1C3 has been reported to impact in intra-tumoral production of androgens and estrogens and thus, might promote Tamoxifen resistance in breast cancer. Over-expression of RORa1 and subsequently AKR1C3 does promote Tamoxifen resistance, which can be inhibited by melatonin administration.

Premise of research. Root traits are influenced by a large number of genes, many of which are environmentally sensitive. Despite a growing body of knowledge on root architecture, we have limited un...

Ultraviolet radiation-induced DNA mutations are a primary environmental driver of melanoma. The reason for this very high level of unrepaired DNA lesions leading to these mutations is still poorly understood. The primary DNA repair mechanism for UV-induced lesions, that is, the nucleotide excision repair pathway, appears intact in most melanomas. We have previously reported a postreplication repair mechanism that is commonly defective in melanoma cell lines. Here we have used a genome-wide approach to identify the components of this postreplication repair mechanism. We have used differential transcript polysome loading to identify transcripts that are associated with UV response, and then functionally assessed these to identify novel components of this repair and cell cycle checkpoint network. We have identified multiple interaction nodes, including global genomic nucleotide excision repair and homologous recombination repair, and previously unexpected MASTL pathway, as components of the response. Finally, we have used bioinformatics to assess the contribution of dysregulated expression of these pathways to the UV signature mutation load of a large melanoma cohort. We show that dysregulation of the pathway, especially the DNA damage repair components, are significant contributors to UV mutation load, and that dysregulation of the MASTL pathway appears to be a significant contributor to high UV signature mutation load.

Excess adiposity is a risk factor for several cancer types. This is likely due to complex mechanisms including alterations in the lipid milieu that plays a pivotal role in multiple aspects of carcinogenesis. Here we consider the direct role of lipids in regulating well-known hallmarks of cancer. Furthermore, we suggest that obesity-associated remodelling of membranes and organelles drives cancer cell proliferation and invasion. Identification of cancer-related lipid-mediated mechanisms amongst the broad metabolic disturbances due to excess adiposity is central to the identification of novel and more efficacious prevention and intervention strategies.

Background Less than 5% of medulloblastoma (MB) patients survive following failure of contemporary radiation-based therapies. Understanding the molecular drivers of medulloblastoma relapse (rMB) will be essential to improve outcomes. Initial genome-wide investigations have suggested significant genetic divergence of the relapsed disease. Methods We undertook large-scale integrated characterization of the molecular features of rMB—molecular subgroup, novel subtypes, copy number variation (CNV), and driver gene mutation. 119 rMBs were assessed in comparison with their paired diagnostic samples (n = 107), alongside an independent reference cohort sampled at diagnosis (n = 282). rMB events were investigated for association with outcome post-relapse in clinically annotated patients (n = 54). Results Significant genetic evolution occurred over disease-course; 40% of putative rMB drivers emerged at relapse and differed significantly between molecular subgroups. Non-infant MBSHH displayed significantly more chromosomal CNVs at relapse (TP53 mutation-associated). Relapsed MBGroup4 demonstrated the greatest genetic divergence, enriched for targetable (eg, CDK amplifications) and novel (eg, USH2A mutations) events. Importantly, many hallmark features of MB were stable over time; novel subtypes (>90% of tumors) and established genetic drivers (eg, SHH/WNT/P53 mutations; 60% of rMB events) were maintained from diagnosis. Critically, acquired and maintained rMB events converged on targetable pathways which were significantly enriched at relapse (eg, DNA damage signaling) and specific events (eg, 3p loss) predicted survival post-relapse. Conclusions rMB is characterised by the emergence of novel events and pathways, in concert with selective maintenance of established genetic drivers. Together, these define the actionable genetic landscape of rMB and provide a basis for improved clinical management and development of stratified therapeutics, across disease-course.

1ABSTRACTThe liver fluke, Fasciola hepatica, is a global burden on the wellbeing and productivity of farmed ruminants, and a zoonotic threat to human health. Despite the clear need for accelerated discovery of new drug and vaccine treatments for this pathogen, we still have a relatively limited understanding of liver fluke biology and host interactions. Noncoding RNAs, including micro (mi)RNAs, are key to transcriptional regulation in all eukaryotes, such that an understanding of miRNA biology can shed light on organismal function at a systems level. Four previous publications have reported up to 89 mature miRNA sequences from F. hepatica, but our data show that this does not represent a full account of this species miRNome. We have expanded on previous studies by sequencing, for the first time, miRNAs from multiple life stages (adult, newly excysted juvenile (NEJ), metacercariae and adult-derived extracellular vesicles (EVs)). These experiments detected an additional 61 high-confidence miRNAs, most of which have not been described in any other species, expanding the F. hepatica miRNome to 150 mature sequences. We used quantitative (q)PCR assays to provide the first developmental profile of miRNA expression across metacercariae, NEJ, adult and adult-derived Evs. The majority of miRNAs were expressed most highly in metacercariae, with at least six distinct expression clusters apparent across life stages. Intracellular miRNAs were functionally analysed to identify target mRNAs with inversely correlated expression in F. hepatica tissue transcriptomes, highlighting regulatory interactions with key virulence transcripts including cathepsin proteases, and neuromuscular genes that control parasite growth, development and motility. We also linked 28 adult-derived EV miRNAs with downregulation of 397 host genes in F. hepatica-infected transcriptomes from ruminant lymph node, peripheral blood mononuclear cell (PBMC) and liver tissue transcriptomes. These included genes involved in signal transduction, immune and metabolic pathways, adding to the evidence for miRNA-based immunosuppression during fasciolosis. These data expand our understanding of the F. hepatica miRNome, provide the first data on developmental miRNA regulation in this species, and provide a set of testable hypotheses for functional genomics interrogations of liver fluke miRNA biology.CONTRIBUTION TO THE FIELDPrevious studies identified 89 micro (mi)RNAs (non-coding RNAs responsible for regulating gene expression) in the trematode parasite, Fasciola hepatica, and attached functional annotations to the miRNAs that are secreted by liver fluke in vitro. This study expands the known miRNA complement of F. hepatica by 40%, adding an additional 61 miRNAs, many of which appear Fasciola-specific. We used this expanded dataset to perform the first analysis of developmental miRNA expression across intra-mammalian parasites, showing clear developmentally regulated expression profiles across infectious metacercariae, juvenile and adult parasites, and extracellular vesicles secreted by adult parasites. We performed rigorous functional annotation of cellular miRNAs, correlating their expression with mRNA transcriptomes to identify potential roles for specific miRNAs in regulating expression of important proteases and nerve/muscle transcripts, all of which are important for parasite virulence. We also functionally analysed miRNAs secreted by adult parasites in terms of interactions with host transcripts; for the first time this analysis was supported by host transcriptome data, linking secreted miRNAs with mRNAs that are downregulated by fluke infection in sheep and cattle. This work contributes new data, insights and analyses to the field, providing a rich source of hypotheses for future experimental validation.

The ocean represents the largest biome on earth; however, we have only begun to understand the diversity and function of the marine microbial inhabitants and their interactions with macroalgal species. Macroalgae play an integral role in overall ocean biome health and serve both as major primary producers and foundation species in the ecosystem. Previous studies have been limited, focusing on the microbiome of a single algal species or its interaction with selected microbes. This project aimed to understand overall biodiversity of microbial communities associated with five common macroalgal species and to determine the drivers of these communities at ‘Ewa Beach, O‘ahu, HI. Representative species of Chlorophyta (green), Ochrophyta (brown), and Rhodophyta (red) algae, each species having various levels of calcification, thallus complexity, and status as native or invasive species, were collected from an intertidal bench in May 2019. A portion of the V3-V4 variable region of the small-subunit rRNA gene was amplified for high-throughput sequencing using universal bacterial primers to elucidate the core and variable algal microbiome. Significant differences in bacterial community composition were only partially explained by host species, whether the host was native or invasive, and thallus complexity. Macroalgal phylum explained the most variation in associated microbial communities at ‘Ewa Beach. This study advances our understanding of microbial-macroalgal interactions and their connectivity by producing insight into factors that influence the community structure of macroalga-associated microbiota. IMPORTANCE Generally, most eukaryotic organisms form relationships with microbes that are important in mediating host organismal health. Macroalgae are a diverse group of photosynthetic eukaryotic organisms that serve as primary producers and foundational species in many ecosystems. However, little is known about their microbial counterparts across a wide range of macroalgal morphologies, phylogenies, and calcification levels. Thus, to further understand the factors involved in bacterial community composition associated with macroalgal species at one point in time, representative samples were collected across phyla. Here, we show that both host macroalga phyla and morphology influenced the associated microbial community. Additionally, we show that the invasive species Avrainvillea lacerata does not have a unique microbial community on this intertidal bench, further supporting the idea that host phylum strongly influences microbial community composition.

Summary Substrate-borne vibratory signals are thought to be one of the most ancient and taxonomically widespread communication signals among animal species, including Drosophila flies.1, 2, 3, 4, 5, 6, 7, 8, 9 During courtship, the male Drosophila abdomen tremulates (as defined in Busnel et al.10) to generate vibrations in the courting substrate.8,9 These vibrations coincide with nearby females becoming immobile, a behavior that facilitates mounting and copulation.8,11, 12, 13 It was unknown how the Drosophila female detects these substrate-borne vibratory signals. Here, we confirm that the immobility response of the female to the tremulations is not dependent on any air-borne cue. We show that substrate-borne communication is used by wild Drosophila and that the vibrations propagate through those natural substrates (e.g., fruits) where flies feed and court. We examine transmission of the signals through a variety of substrates and describe how each of these substrates modifies the vibratory signal during propagation and affects the female response. Moreover, we identify the main sensory structures and neurons that receive the vibrations in the female legs, as well as the mechanically gated ion channels Nanchung and Piezo (but not Trpγ) that mediate sensitivity to the vibrations. Together, our results show that Drosophila flies, like many other arthropods, use substrate-borne communication as a natural means of communication, strengthening the idea that this mode of signal transfer is heavily used and reliable in the wild.3,4,7 Our findings also reveal the cellular and molecular mechanisms underlying the vibration-sensing modality necessary for this communication., Graphical abstract, Highlights • Courting male abdominal tremulations signal via substrate-borne, not air-borne, vibrations • Substrate-borne vibrations propagate through natural food substrates • Neurons of the leg fCHO mediate female immobility response to these vibrations • Mechanically gated ion channels Nan and Piezo mediate response in these neurons, McKelvey et al. find that courting male D. melanogaster abdominal tremulations signal via substrate-borne, not air-borne, vibrations. These vibrations propagate through natural food substrates, promoting female immobility. Neurons and their mechanically gated ion channels within the leg fCHO mediate female response to the vibrations.

Author(s): Dudzinski, Kathleen M; Hill, Heather M; Zaccaroni, Annalisa; Makecha, Radhika; Lilly, Malin; Almunia, Javier; Frick, Erin; Feucht, Todd; Stafford, Grey; Abramson, Charles I. | Abstract: We contest publication of Marino et al. regarding captive killer whale (Orcinus orca) welfare because of misrepresentations of available data and the use of citations that do not support assertions. Marino et al. misrepresent stress response concepts and erroneously cite studies, which appear to support Marino et al.’s philosophical beliefs regarding the cetacean hypothalamic–pituitary–adrenal axis. To be clear, these misrepresentations are not differences of scientific opinion, as the authors’ conclusions lack any scientific basis. More extensive review of Marino et al.’s citations reveal a dearth of empirical evidence to support their assertions. Further, Marino et al.’s approach to animal welfare is not consistent with conventional veterinary approaches to animal welfare, including their apparent opposition to use of preventative and therapeutic veterinary interventions. While Marino et al. argue that killer whales’ cognitive and spatial needs preclude management of this species under human care, misrepresentation of the citations used to support this opinion invalidates their arguments. Misleading interpretations of data relative to killer whales’ cognitive and emotional needs and specious and unsubstantiated comparisons with states experienced by humans with posttraumatic stress disorder and other conditions, represent a number of strategies used to misrepresent knowledge regarding killer whale welfare. These misrepresentations and fallacies are inconsistent with scientific ethical standards for credible, peer-reviewed journals (ICMJE, 2018), and are barriers to rigorous discourse and identification of strategies for optimizing killer whale welfare. Assertions in the paper amount to nothing more than a compilation of conclusory, philosophical statements. We would also like to mention that manuscripts such as Marino et al.’s do great damage to the fields of comparative psychology and to behavioral science as a whole.

Maturation rate of malaria parasites within red blood cells (RBC) can be influenced by host nutrient status or circadian rhythm. Here, we observed in mice that systemic host inflammation, induced by lipopolysaccharide (LPS) conditioning or ongoing acute malaria infection, slowed the progression of a single cohort of parasites from one generation of RBC to the next. LPS-conditioning and acute infection both triggered substantial changes to the metabolomic composition of plasma in which parasites circulated. This altered plasma directly slowed parasite maturation in a manner that could not be rescued by supplementation, consistent with the presence of inhibitory factors. Single-cell transcriptomic assessment of mixed parasite populations, exposed to a short period of systemic host inflammation in vivo, revealed specific impairment in the transcriptional activity and translational capacity of trophozoites compared to rings or schizonts. Thus, we provide in vivo evidence of transcriptomic and phenotypic plasticity of asexual blood-stage Plasmodium parasites when exposed to systemic host inflammation.

CRISPR-associated transposons (CASTs) co-opt Cas genes for RNA-guided transposition. CASTs are exceedingly rare in genomic databases; recent surveys have reported Tn7-like transposons that co-opt Type I-F, I-B, and V-K CRISPR effectors. Here, we expand the diversity of reported CAST systems via a bioinformatic search of metagenomic databases. We discover new architectures for all known CASTs, including novel arrangements of the Cascade effectors, new self-targeting modalities, and minimal V-K systems. We also describe new families of CASTs that have co-opted the Type I-C and Type IV CRISPR-Cas systems. Our search for non-Tn7 CASTs identifies putative candidates that co-opt Cas12a for horizontal gene transfer. These new systems shed light on how CRISPR systems have co-evolved with transposases and expand the programmable gene editing toolkit.

Background Brain-computer interfaces decode intentions directly from the human brain with the aim to restore lost functionality, control external devices or augment daily experiences. To combine optimal performance with wide applicability, high-quality brain signals should be captured non-invasively. Magnetoencephalography (MEG) is a potent candidate but currently requires costly and confining recording hardware. The recently developed optically pumped magnetometers (OPMs) promise to overcome this limitation, but are currently untested in the context of neural interfacing. Results In this work, we show that OPM-MEG allows robust single-trial analysis which we exploited in a real-time ‘mind-spelling’ application yielding an average accuracy of 97.7%. Conclusions This shows that OPM-MEG can be used to exploit neuro-magnetic brain responses in a practical and flexible manner, and opens up new avenues for a wide range of new neural interface applications in the future.

As a countermeasure to the SARS-CoV-2 pandemic, there has been swift development and clinical trial assessment of candidate vaccines, with subsequent deployment as part of mass vaccination campaigns. However, the SARS-CoV-2 virus has demonstrated the ability to mutate and develop variants, which can modify epidemiological properties and potentially also the effectiveness of vaccines. The widespread deployment of highly effective vaccines may rapidly exert selection pressure on the SARS-CoV-2 virus directed towards mutations that escape the vaccine-induced immune response. This is particularly concerning while infection is widespread. By developing and analysing a mathematical model of two population groupings with differing vulnerability and contact rates, we explore the impact of the deployment of vaccines among the population on the reproduction ratio, cases, disease abundance and vaccine escape pressure. The results from this model illustrate two insights: (i) vaccination aimed at reducing prevalence could be more effective at reducing disease than directly vaccinating the vulnerable; (ii) the highest risk for vaccine escape can occur at intermediate levels of vaccination. This work demonstrates a key principle: the careful targeting of vaccines towards particular population groups could reduce disease as much as possible while limiting the risk of vaccine escape.

Simple Summary Triple-negative breast cancer (TNBC) tends to occur in younger women, is aggressive and has a poor outcome due to limited therapies. Recent drug trials have shown promise, but only improved TNBC survival by several months. To discover potential new therapeutic targets and pathways, we focused on the known alteration of glycosylation in cancer, and sought to discover TNBC-specific glycogenes and their regulatory pathways. Using an integrative bioinformatics approach, we discovered 34 TNBC-specific candidate glycogenes, and identified the lacto-/neolacto- glycosphingolipid biosynthesis pathway with seven candidate glycogenes as a novel target in TNBC. Furthermore, we identified three transcription factors as potential therapeutic targets: AR, GATA3 and ZNF622. Each TF target three glycogenes in this pathway. Together, this study revealed novel molecular features of TNBC, identifying potential new therapeutic targets. Abstract Triple-negative breast cancer (TNBC) is an aggressive breast cancer with limited treatment options. Glycosylation has been implicated in cancer development, but TNBC-specific glycosylation pathways have not been examined. Here, we applied bioinformatic analyses on public datasets to discover TNBC-specific glycogenes and pathways, as well as their upstream regulatory mechanisms. Unsupervised clustering of 345 glycogene expressions in breast cancer datasets revealed a relative homogenous expression pattern in basal-like TNBC subtype. Differential expression analyses of the 345 glycogenes between basal-like TNBC (hereafter termed TNBC) and other BC subtypes, or normal controls, revealed 84 differential glycogenes in TNBC. Pathway enrichment showed two common TNBC-enriched pathways across all three datasets, cell cycle and lacto-/neolacto- glycosphingolipid (GSL) biosynthesis, while a total of four glycosylation-related pathways were significantly enriched in TNBC. We applied a selection criterion of the top 50% differential anabolic/catabolic glycogenes in the enriched pathways to define 34 TNBC-specific glycogenes. The lacto-/neolacto- GSL biosynthesis pathway was the most highly enriched, with seven glycogenes all up-regulated in TNBC. This data led us to investigate the hypothesis that a common upstream mechanism in TNBC up-regulates the lacto-/neolacto-GSL biosynthesis pathway. Using public multi-omic datasets, we excluded the involvement of copy-number alteration and DNA methylation, but identified three transcription factors (AR, GATA3 and ZNG622) that each target three candidate genes in the lacto-/neolacto- GSL biosynthesis pathway. Interestingly, a subset of TNBC has been reported to express AR and GATA3, and AR antagonists are being trialed for TNBC. Our findings suggest that AR and GATA3 may contribute to TNBC via GSL regulation, and provide a list of candidate glycogenes for further investigation.

Viral reproduction of SARS-CoV-2 provides opportunities for the acquisition of advantageous mutations, altering viral transmissibility, disease severity, and/or allowing escape from natural or vaccine-derived immunity. We use three mathematical models: a parsimonious deterministic model with homogeneous mixing; an age-structured model; and a stochastic importation model to investigate the effect of potential variants of concern (VOCs). Calibrating to the situation in England in May 2021, we find epidemiological trajectories for putative VOCs are wide-ranging and dependent on their transmissibility, immune escape capability, and the introduction timing of a postulated VOC-targeted vaccine. We demonstrate that a VOC with a substantial transmission advantage over resident variants, or with immune escape properties, can generate a wave of infections and hospitalisations comparable to the winter 2020-2021 wave. Moreover, a variant that is less transmissible, but shows partial immune-escape could provoke a wave of infection that would not be revealed until control measures are further relaxed., Understanding the potential impacts of new variants of SARS-CoV-2 is important for pandemic planning. Here, the authors develop a model incorporating hypothetical new variants with varying transmissibility and immune evasion properties, and use it to project possible future epidemic waves in the UK.

Success and impact metrics in science are based on a system that perpetuates sexist and racist “rewards” by prioritizing citations and impact factors. These metrics are flawed and biased against already marginalized groups and fail to accurately capture the breadth of individuals’ meaningful scientific impacts. We advocate shifting this outdated value system to advance science through principles of justice, equity, diversity, and inclusion. We outline pathways for a paradigm shift in scientific values based on multidimensional mentorship and promoting mentee well-being. These actions will require collective efforts supported by academic leaders and administrators to drive essential systemic change., This Essay argues that success and impact metrics in science are based on a system that perpetuates sexist and racist ‘rewards’ by prioritizing citations and impact factors; the authors advocate shifting this outdated value system to advance science through principles of justice, equity, diversity, and inclusion.

The rapid emergence of SARS-CoV-2 mutants with new phenotypic properties is a critical challenge to the control of the ongoing pandemic. B.1.1.7 was monitored in the UK through routine testing and S-gene target failures (SGTF), comprising over 90% of cases by March 2021. Now, the reverse is occurring: SGTF cases are being replaced by an S-gene positive variant, which we associate with B.1.617.2. Evidence from the characteristics of S-gene positive cases demonstrates that, following importation, B.1.617.2 is transmitted locally, growing at a rate higher than B.1.1.7 and a doubling time between 5-14 days. S-gene positive cases should be prioritised for sequencing and aggressive control in any countries in which this variant is newly detected.One-Sentence SummaryThe B.1.617.2 variant of SARS-CoV-2 is replacing B.1.1.7 and emerging as the dominant variant in England, evidenced by sustained local transmission.

Light is a potent biologic force that profoundly influences circadian, neuroendocrine, and neurobehavioral regulation in animals. Previously we examined the effects of light-phase exposure of rats to white light-emitting diodes (LED), which emit more light in the blue-appearing portion of the visible spectrum (465 to 485 nm) than do broad-spectrum cool white fluorescent (CWF) light, on the nighttime melatonin amplitude and circadian regulation of metabolism and physiology. In the current studies, we tested the hypothesis that exposure to blue-enriched LED light at day (bLAD), compared with CWF, promotes the circadian regulation of neuroendocrine, metabolic, and physiologic parameters that are associated with optimizing homeostatic regulation of health and wellbeing in 3 mouse strains commonly used in biomedical research (C3H [melatonin-producing], C57BL/6, and BALB/c [melatonin-non-producing]). Compared with male and female mice housed for 12 wk under 12:12-h light:dark (LD) cycles in CWF light, C3H mice in bLAD evinced 6-fold higher peak plasma melatonin levels at the middark phase; in addition, high melatonin levels were prolonged 2 to 3 h into the light phase. C57BL/6 and BALB/c strains did not produce nighttime pineal melatonin. Body growth rates; dietary and water intakes; circadian rhythms of arterial blood corticosterone, insulin, leptin, glucose, and lactic acid; pO2 and pCO2; fatty acids; and metabolic indicators (cAMP, DNA, tissue DNA 3H-thymidine incorporation, fat content) in major organ systems were significantly lower and activation of major metabolic signaling pathways (mTOR, GSK3β, and SIRT1) in skeletal muscle and liver were higher only in C3H mice in bLAD compared with CWF. These data show that exposure of C3H mice to bLAD compared with CWF has a marked positive effect on the circadian regulation of neuroendocrine, metabolic, and physiologic parameters associated with the promotion of animal health and wellbeing that may influence scientific outcomes. The absence of enhancement in amelatonic strains suggests hyperproduction of nighttime melatonin may be a key component of the physiology.

Largemouth bass Micropterus salmoides is a highly successful predator that preys on fish and invertebrates. Highly popular with anglers, it is one of the most introduced and invasive fish globally,...

The order Piroplasmida contains a diverse group of intracellular parasites, many of which can cause significant disease in humans, domestic animals, and wildlife. Two piroplasm species have been reported from raccoons (Procyon lotor), Babesia lotori (Babesia sensu stricto clade) and a species related to Babesia microti (called B. microti-like sp.). The goal of this study was to investigate prevalence, distribution, and diversity of Babesia in raccoons. We tested raccoons from selected regions in the United States and Canada for the presence of Babesia sensu stricto and Babesia microti-like sp. piroplasms. Infections of Babesia microti-like sp. were found in nearly all locations sampled, often with high prevalence, while Babesia sensu stricto infections had higher prevalence in the Southeastern United States (20–45% prevalence). Co-infections with both Babesia sp. were common. Sequencing of the partial 18S rRNA and cytochrome oxidase subunit 1 (cox1) genes led to the discovery of two new Babesia species, both found in several locations in the eastern and western United States. One novel Babesia sensu stricto sp. was most similar to Babesia gibsoni while the other Babesia species was present in the ‘western piroplasm’ group and was related to Babesia conradae. Phylogenetic analysis of the cox1 sequences indicated possible eastern and western genetic variants for the three Babesia sensu stricto species. Additional analyses are needed to characterize these novel species; however, this study indicates there are now at least four species of piroplasms infecting raccoons in the United States and Canada (Babesia microti-like sp., Babesia lotori, a novel Babesia sensu stricto sp., a novel western Babesia sp.) and a possible fifth species (Babesia sensu stricto) in raccoons in Japan., Graphical abstract Image 1, Highlights • Raccoons in all locations tested were infected with piroplasms. • Babesia microti-like sp. was commonly found in raccoons throughout North America. • Babesia sensu stricto spp. were less common throughout North America. • Four, possibly five, distinct species of piroplasms in raccoons. • Possible spatial genetic variation within the two raccoon piroplasm species.

Oxandrolone has proven benefits in thermal burn injury and has become a standard of care. Transaminitis is the most frequent side effect of oxandrolone use, although no risk factors have been identified that increase the risk of transaminitis. The objective was to evaluate the frequency of transaminitis while on oxandrolone and to identify risk factors leading to an increased risk of transaminitis in adult burn patients. This multicenter retrospective risk factor analysis compared two patient groups with and without occurrence of transaminitis, which was detected by an aspartate aminotransferase (AST) or alanine aminotransferase (ALT) >100 mg/dL. Secondary outcomes included percentage increase from baseline for AST/ALT, length of stay, and mortality. After univariable analysis, a multivariable logistic regression analysis was performed to detect possible risk factors leading to transaminitis. A total of 309 patients were included, with transaminitis occurring in 128 patients (41.4%) after 13 (interquartile range [IQR] 8–23) days on oxandrolone. After multivariable analysis, age (odds ratio [OR] 0.91; 95% confidence interval [CI] 0.84–0.99 for a 5-year increase in age), intravenous vasopressor use (OR 1.85; 95% CI 1.05–3.27), and amiodarone use (OR 2.51; 95% CI 1.09–5.77) were independent predictors of transaminitis, controlling for TBSA%. Transaminitis was not significantly associated with length of stay or mortality after adjusting for age and TBSA%. We conclude that patients who are younger and have concurrent amiodarone or vasopressor use have the highest risk of developing oxandrolone induced transaminitis and should be monitored closely.

Heart failure with preserved ejection fraction (HFpEF) is a common syndrome with high morbidity and mortality for which there are no evidence-based therapies. Here we report that concomitant metabolic and hypertensive stress in mice—elicited by a combination of high-fat diet and inhibition of constitutive nitric oxide synthase using Nω-nitro-l-arginine methyl ester (l-NAME)—recapitulates the numerous systemic and cardiovascular features of HFpEF in humans. Expression of one of the unfolded protein response effectors, the spliced form of X-box-binding protein 1 (XBP1s), was reduced in the myocardium of our rodent model and in humans with HFpEF. Mechanistically, the decrease in XBP1s resulted from increased activity of inducible nitric oxide synthase (iNOS) and S-nitrosylation of the endonuclease inositol-requiring protein 1α (IRE1α), culminating in defective XBP1 splicing. Pharmacological or genetic suppression of iNOS, or cardiomyocyte-restricted overexpression of XBP1s, each ameliorated the HFpEF phenotype. We report that iNOS-driven dysregulation of the IRE1α–XBP1 pathway is a crucial mechanism of cardiomyocyte dysfunction in HFpEF. iNOS-driven dysregulation of the IRE1α–XBP1 pathway leads to cardiomyocyte dysfunction in mice and recapitulates the systemic and cardiovascular features of human heart failure with preserved ejection fraction.

A unique symbiosis occurs between embryos of the spotted salamander (Ambystoma maculatum) and a green alga (Oophila amblystomatis). Unlike most vertebrate host-symbiont relationships, which are ectosymbiotic, A. maculatum exhibits both an ecto- and an endo-symbiosis, where some of the green algal cells living inside egg capsules enter embryonic tissues as well as individual salamander cells. Past research has consistently categorized this symbiosis as a mutualism, making this the first example of a “beneficial” microbe entering vertebrate cells. Another closely related species of salamander, Ambystoma gracile, also harbors beneficial Oophila algae in its egg capsules. However, our sampling within the A. gracile range consistently shows this to be a strict ectosymbiotic interaction—with no sign of tissue or presumably cellular entry. In this study we swapped cultured algae derived from intracapsular fluid of different salamander hosts to test the fidelity of tissue entry in these symbioses. Both A. maculatum and A. gracile embryos were raised in cultures with their own algae or algae cultured from the other host. Under these in vitro culture conditions A. maculatum algae will enter embryonic A. maculatum tissues. Additionally, although at a much lower frequency, A. gracile derived algae will also enter A. maculatum host tissues. However, neither Oophila strain enters A. gracile hosts in these co-culture conditions. These data reveal a potential host-symbiont fidelity that allows the unique endosymbiosis to occur in A. maculatum, but not in A. gracile. However, preliminary trials in our study found that persistent endogenous A. maculatum algae, as opposed to the cultured algae used in subsequent trials, enters host tissues at a higher frequency. An analysis of previously published Oophila transcriptomes revealed dramatic differences in gene expression between cultured and intracapsular Oophila. These include a suite of genes in protein and cell wall synthesis, photosynthesis, central carbon metabolism suggesting the intracapsular algae are assimilating ammonia for nitrogen metabolism and may be undergoing a life-cycle transition. Further refinements of these co-culture conditions could help determine physiological differences between cultured and endogenous algae, as well as rate-limiting cues provided for the alga by the salamander.

Livestock have presented unique requirements and toxicity issues depending on the species for the various concentrations of Cu and Zn and their interactions with other nutrients especially Fe, Se, Mo, and S. Soil concentrations of these elements and their availability to crops influence the health of the crop and the amount found in vegetative tissues and seeds. Hence, many livestock issues are a result of the soils in the area where production is occurring (Loneragan et al. 1981). While water can provide minerals to animals, the amount consumed and availability are highly variable. Many discoveries about Cu were a result of low Cu concentrations and its availability due to interactions with other nutrients in the soils. Anemia, bone disorders, cardiovascular abnormalities, defective wool and hair, and infertility are signs/symptoms of Cu deficiency. Toxicity due to excess Cu is more likely to occur in sheep than other farm species. Swine are tolerant of high concentrations of dietary Cu, and it is often used as a growth stimulant in production. There are many species and physiological stages where the animal's Cu requirement is not known. Grazing animals can exhibit Zn deficiency when soils and forages contain limited concentrations of Zn. Pastures have been observed to be Zn-deficient in many parts of the world. However, non-ruminant animals usually receive adequate Zn when fed corn and soybean meal diets if there is not excessive Ca and Fe in their diets, but this is not true for rapidly growing young animals. Characteristics of a Zn deficiency include loss of appetite, reduced growth and reproduction, and impaired health of bone and skin tissues.

Light is a key extrinsic factor to be considered in operations and design of animal room facilities. Over the past four decades, many studies on typical laboratory animal populations have demonstrated impacts on neuroendocrine, neurobehavioral, and circadian physiology. These effects are regulated independently from the defined physiology for the visual system. The range of physiological responses that oscillate with the 24 hour rhythm of the day include sleep and wakefulness, body temperature, hormonal secretion, and a wide range of other physiological parameters. Melatonin has been the chief neuroendocrine hormone studied, but acute light-induced effects on corticosterone as well as other hormones have also been observed. Within the last two decades, a new photosensory system in the mammalian eye has been discovered. A small set of retinal ganglion cells, previously thought to function as a visual output neuron, have been shown to be directly photosensitive and act differently from the classic photoreceptors of the visual system. Understanding the effects of light on mammalian physiology and behavior must take into account how the classical visual photoreceptors and the newly discovered ipRGC photoreceptor systems interact. Scientists and facility managers need to appreciate lighting impacts on circadian, neuroendocrine, and neurobehavioral regulation in order to improve lighting of laboratory facilities to foster optimum health and well-being of animals.

Background and Aims Determining seed longevity by identifying chemical changes that precede, and may be linked to, seed mortality, is an important but difficult task. The standard assessment, germination proportion, reveals seed longevity by showing that germination proportion declines, but cannot be used to predict when germination will be significantly compromised. Assessment of molecular integrity, such as RNA integrity, may be more informative about changes in seed health that precede viability loss, and has been shown to be useful in soybean. Methods A collection of seeds stored at 5 °C and 35–50 % relative humidity for 1–30 years was used to test how germination proportion and RNA integrity are affected by storage time. Similarly, a collection of seeds stored at temperatures from −12 to +32 °C for 59 years was used to manipulate ageing rate. RNA integrity was calculated using total RNA extracted from one to five seeds per sample, analysed on an Agilent Bioanalyzer. Results Decreased RNA integrity was usually observed before viability loss. Correlation of RNA integrity with storage time or storage temperature was negative and significant for most species tested. Exceptions were watermelon, for which germination proportion and storage time were poorly correlated, and tomato, which showed electropherogram anomalies that affected RNA integrity number calculation. Temperature dependencies of ageing reactions were not significantly different across species or mode of detection. The overall correlation between germination proportion and RNA integrity, across all experiments, was positive and significant. Conclusions Changes in RNA integrity when ageing is asymptomatic can be used to predict onset of viability decline. RNA integrity appears to be a metric of seed ageing that is broadly applicable across species. Time and molecular mobility of the substrate affect both the progress of seed ageing and loss of RNA integrity.