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Thermal biology research compares field with laboratory data to elucidate the evolution of temperature-sensitive traits in ectotherms. The hidden challenge of many of these studies is discerning whether animals actively thermoregulate, since motivation is not typically assessed. By studying the behaviours involved in thermoregulation, we can better understand the mechanisms underlying body temperature control. Using an integrative approach, we assessed the thermoregulatory and thermotactic behaviours of two sympatric snake species with contrasting life histories: the generalist Eastern Garter Snake (Thamnophis sirtalis sirtalis ( Linnaeus, 1758 )) and the semi-fossorial Northern Red-bellied Snake (Storeria occipitomaculata occipitomaculata ( Storer, 1839 )). We expected that thermoregulatory behaviours would be optimized based on life history, in that T. s. sirtalis would show higher evidence for thermally oriented behaviours than S. o. occipitomaculata due to its active nature. Thamnophis sirtalis sirtalis actively thermoregulated, had higher thermal preferences (29.4 ± 2.5 vs. 25.3 ± 3.6 °C), and was more active than S. o. occipitomaculata, which showed relatively low evidence for thermotaxis. Our results build on the notion that evaluating movement patterns and rostral orientation towards a heat source can help ascertain whether animals make thermally motivated choices. Our data provide insight into the thermoregulatory strategies used by snakes with different life histories and maximize the information provided by behavioural thermoregulation experiments.

Naked mole-rats are among the most hypoxia-tolerant mammals. During hypoxia, their body temperature (Tb) decreases via unknown mechanisms to conserve energy. In small mammals, non-shivering thermogenesis in brown adipose tissue (BAT) is critical to Tb regulation; therefore, we hypothesize that hypoxia decreases naked mole-rat BAT thermogenesis. To test this, we measure changes in Tb during normoxia and hypoxia (7% O2; 1–3 h). We report that interscapular thermogenesis is high in normoxia but ceases during hypoxia, and Tb decreases. Furthermore, in BAT from animals treated in hypoxia, UCP1 and mitochondrial complexes I-V protein expression rapidly decrease, while mitochondria undergo fission, and apoptosis and mitophagy are inhibited. Finally, UCP1 expression decreases in hypoxia in three other social African mole-rat species, but not a solitary species. These findings suggest that the ability to rapidly down-regulate thermogenesis to conserve oxygen in hypoxia may have evolved preferentially in social species., Naked mole-rats are hypoxia-tolerant mammals, and during hypoxia their body temperature decreases via unknown mechanisms. Here the authors report that the hypoxia-induced body temperature decrease in naked mole rats occurs through decreased brown adipose tissue thermogenesis via decreases in a key thermogenic mitochondrial protein: UCP1.

Many animal appendages, such as avian beaks and mammalian ears, can be used to dissipate excess body heat. Allen's rule, wherein animals in warmer climates have larger appendages to facilitate more efficient heat exchange, reflects this. We find that there is widespread evidence of 'shape-shifting' (changes in appendage size) in endotherms in response to climate change and its associated climatic warming. We re-examine studies of morphological change over time within a thermoregulatory context, finding evidence that temperature can be a strong predictor of morphological change independently of, or combined with, other environmental changes. Last, we discuss how Allen's rule, the degree of temperature change, and other ecological factors facilitate morphological change and make predictions about what animals will show shape-shifting.

Many natural and managed organisms will require substantial functional genetic variation to respond to selection in the face of rapid environmental change. Pacific salmon have experienced strong fluctuations in critical fitness traits over the past five decades. We examined genetic and phenotypic variability over three generations in a pedigreed hatchery population of coho salmon (Oncorhynchus kisutch) by monitoring seven fitness-related traits. Three-year-old adult return numbers varied more than fivefold, and jack (2-year-old males) numbers varied 13-fold. Body sizes of Inch Creek coho salmon decreased consistently such that fish were only 40.7% as heavy in 2015 as in 2006, and female reproductive traits also decreased. During the study period, the majority of families produced returning adult progeny, and effective population size was relatively constant. Heritability estimates for phenotypic traits were significantly greater than zero except for condition factor, and the estimated heritability for jacking was 0.42. The Inch Creek coho salmon population harbours substantial heritability for fitness and reproductive traits and thus likely retains substantial capacity for adaptation despite many years of hatchery propagation.

Regulating body temperature is a critical function for many animals. Ectotherms use multiple thermoregulatory behaviours, including habitat selection, sun-shade shuttling, posture, orientation, gaping, and panting. According to thermoregulatory control theory, gaping and postural behaviours should act in coordination with microhabitat selection, providing a fine-tuned counterbalance to more costly behaviours. However, gaping and panting have also been considered indicators of stress in lizards, which would counter a homeostatic thermoregulatory interpretation, especially during expression of voluntary behaviours. Careful adjustments in rostral orientation toward warmth have been observed in bearded dragons, analogous to well-described solar gain and solar avoidance postures in the wild. Little is known about the sensory drivers of these behaviours. Although skin temperature changes faster than core, it is not uniform across the body, and is subject to evaporative cooling, and thus could be crucial to directing behavioural thermoregulatory decision making. To examine the subtle coordination between thermoregulatory behaviours, and to test if inhibiting gaping would lead to thermoregulatory compensatory behaviours, bearded dragon lizards (Pogona vitticeps) were allowed to behaviourally thermoregulate, while their ability to show spontaneous gaping behaviour was disrupted non-pharmacologically. Gaping acted in concert with thermoregulatory behaviours, although at lower rates than predicted from earlier steady-state models, suggesting that respiratory cooling mechanisms are perceived as costly. Bearded dragons enhanced their rostral orientation to heat when gaping was inhibited, while reducing their selected temperatures in a thermal gradient. Combined, these observations indicate the presence of coordination between these various thermoregulatory behaviours.

Inhibition of acetylcholinesterase by either organophosphates or carbamates causes anti-cholinesterase poisoning. This arises through a wide range of neurotoxic effects triggered by the overstimulation of the cholinergic receptors at synapses and neuromuscular junctions. Without intervention, this poisoning can lead to profound toxic effects, including death, and the incomplete efficacy of the current treatments, particularly for oxime-insensitive agents, provokes the need to find better antidotes. Here we show how the non-parasitic nematode Caenorhabditis elegans offers an excellent tool for investigating the acetylcholinesterase intoxication. The C. elegans neuromuscular junctions show a high degree of molecular and functional conservation with the cholinergic transmission that operates in the autonomic, central and neuromuscular synapses in mammals. In fact, the anti-cholinesterase intoxication of the worm’s body wall neuromuscular junction has been unprecedented in understanding molecular determinants of cholinergic function in nematodes and other organisms. We extend the use of the model organism’s feeding behaviour as a tool to investigate carbamate and organophosphate mode of action. We show that inhibition of the cholinergic-dependent rhythmic pumping of the pharyngeal muscle correlates with the inhibition of the acetylcholinesterase activity caused by aldicarb, paraoxons and DFP exposure. Further, this bio-assay allows one to address oxime dependent reversal of cholinesterase inhibition in the context of whole organism recovery. Interestingly, the recovery of the pharyngeal function after such anti-cholinesterase poisoning represents a sensitive and easily quantifiable phenotype that is indicative of the spontaneous recovery or irreversible modification of the worm acetylcholinesterase after inhibition. These observations highlight the pharynx of C. elegans as a new tractable approach to explore anti-cholinesterase intoxication and recovery with the potential to resolve critical genetic determinants of these neurotoxins’ mode of action.

Small carpenter bees (Ceratina calcarata Robertson) (Hymenoptera: Apidae) build their nests in both sunny and shady sites, so maternal decisions about nest sites influence the thermal environment experienced by juveniles throughout development. A previous study demonstrated that when larvae and pupae were raised in the laboratory at room temperature, those from sunny nests developed more slowly than those from shady nests. This suggested that bees developing in sunny nests slowed their metabolism or that bees developing in shady nests increased their metabolism. To test this hypothesis, we performed a field experiment in which bees nested in full sun, full shade, or semi-shade. We brought larvae and pupae into the laboratory to be raised to adulthood at room temperature and measured their metabolic rates (VCO2) at 10 °C, 25 °C, and 40 °C. As expected, bees had higher VCO2 at higher test temperatures, but significant interaction also occurred between test temperature and field treatment, such that bees from sunny nests exhibited higher metabolic rates at 40 °C. Because small carpenter bees frequently nest in full sun, adaptation to high nest temperatures may involve activation of thermal protection mechanisms at the cost of slower development.

Interspecific interactions are an integral aspect of ecosystem functioning that may be disrupted in an increasingly anthropocentric world. Industrial landscape change creates a novel playing field on which these interactions take place, and a key question for wildlife managers is whether and how species are able to coexist in such working landscapes. Using camera traps deployed in northern Alberta, we surveyed boreal predators to determine whether interspecific interactions affected occurrences of black bears (Ursus americanus), coyotes (Canis latrans), and lynx (Lynx canadensis) within a landscape disturbed by networks of seismic lines (corridors cut for seismic exploration of oil and gas reserves). We tested hypotheses of species interactions across one spatial‐only and two spatiotemporal (daily and weekly) scales. Specifically, we hypothesized that (1) predators avoid competition with the apex predator, gray wolf (Canis lupus), (2) they avoid competition with each other as intraguild competitors, and (3) they overlap with their prey. All three predators overlapped with wolves on at least one scale, although models at the daily and weekly scale had substantial unexplained variance. None of the predators showed avoidance of intraguild competitors or overlap with prey. These results show patterns in predator space use that are consistent with both facilitative interactions or shared responses to unmeasured ecological cues. Our study provides insight into how predator species use the working boreal landscape in relation to each other, and highlights that predator management may indirectly influence multiple species through their interactions., Interspecific interactions are an integral aspect of ecosystem functioning that may be disrupted in an increasingly anthropocentric world. Using camera traps deployed in northern Alberta, we surveyed boreal predators to determine whether interspecific interactions affected occurrences of black bears (Ursus americanus), coyotes (Canis latrans), and lynx (Lynx canadensis) within a seismic line network. Our results highlight important considerations of the impact of predator management decisions, especially in working landscapes shared between wildlife and industry.

Vocal emission requires coordination with the respiratory system. Monitoring the increase in laryngeal pressure, which is needed for vocal production, allows detection of transitions from quiet respiration to vocalization-supporting respiration. Characterization of these transitions could be used to identify preparation for vocal emission and to examine the probability of it manifesting into an actual vocal production event. Specifically, overlaying the subject's respiration with conspecific calls can highlight events of call initiation and suppression, as a means of signalling coordination and avoiding jamming. Here, we present a thermal imaging-based methodology for synchronized respiration and vocalization monitoring of free-ranging meerkats. The sensitivity of this methodology is sufficient for detecting transient changes in the subject's respiration associated with the exertion of vocal production. The differences in respiration are apparent not only during the vocal output, but also prior to it, marking the potential time frame of the respiratory preparation for calling. A correlation between conspecific calls with elongation of the focal subject's respiration cycles could be related to fluctuations in attention levels or in the motivation to reply. This framework can be used for examining the capability for enhanced respiration control in animals during modulated and complex vocal sequences, detecting ‘failed’ vocalization attempts and investigating the role of respiration cues in the regulation of vocal interactions.

Complex biological functions within organisms are frequently orchestrated by systemic communication between tissues. In the model organism Caenorhabditis elegans, the pharyngeal and body wall neuromuscular junctions are two discrete structures that control feeding and locomotion, respectively. Separate, the well-defined neuromuscular circuits control these distinct tissues. Nonetheless, the emergent behaviors, feeding and locomotion, are coordinated to guarantee the efficiency of food intake. Here, we show that pharmacological hyperactivation of cholinergic transmission at the body wall muscle reduces the rate of pumping behavior. This was evidenced by a systematic screening of the effect of the cholinesterase inhibitor aldicarb on the rate of pharyngeal pumping on food in mutant worms. The screening revealed that the key determinants of the inhibitory effect of aldicarb on pharyngeal pumping are located at the body wall neuromuscular junction. In fact, the selective stimulation of the body wall muscle receptors with the agonist levamisole inhibited pumping in a lev-1-dependent fashion. Interestingly, this response was independent of unc-38, an alpha subunit of the nicotinic receptor classically expressed with lev-1 at the body wall muscle. This implies an uncharacterized lev-1-containing receptor underpins this effect. Overall, our results reveal that body wall cholinergic transmission not only controls locomotion but simultaneously inhibits feeding behavior.

Osteosarcoma (OS) is the most common type of primary bone cancer affecting children and adolescents. OS has a high propensity to spread, meaning the disease is often incurable and fatal. There have been no improvements in survival rates for decades. This highlights an urgent need for development of novel therapeutic strategies. In this study, we have produced in vitro and in vivo data that demonstrates the role of purinergic signalling, specifically, the B isoform of the purinergic receptor P2RX7 (herein termed “ P2RX7B”), in OS progression and metastasis. Our data shows that P2RX7B expression confers a survival advantage in TE85+P2RX7B and MNNG-HOS+ P2RX7B human OS cell lines in vitro that is minimised following treatment with A740003, a specific P2RX7 antagonist. P2RX7B expression reduced cell adhesion and P2RX7B activation promoted invasion and migration in vitro, suggesting a probable metastatic phenotype. Using an in vivo OS xenograft model, MNNG-HOS+P2RX7B tumours exhibited ectopic bone formation that was abrogated with A740003 treatment. An increased metastatic phenotype was further demonstrated in vivo as expression of P2RX7B in primary tumour cells increased the propensity of the tumour to metastasise to the lungs. RNA-seq identified a novel gene axis, FN1/LOX/PDGFB/IGFBP3/BMP4, downregulated in response to A740003 treatment. In conclusion, our data indicates for the first time a role for P2RX7B in OS tumour growth, progression and metastasis. We show that P2RX7B is a potential therapeutic target in human OS.Novelty and ImpactWe provide evidence for the pro-tumorigenic role of the B isoform of the P2RX7 purinergic receptor in osteosarcoma (OS). In addition to increasing proliferation, P2RX7B increases the cancerous properties of OS cells, reducing adhesion and increasing migration and invasion. In vivo, P2RX7B does not affect primary tumour growth, but does lead to an increased propensity to metastasize. RNA-seq revealed a new axis of oncogenic genes inhibited by the P2RX7 antagonist and this data could potentially lead to new targets for OS treatment.

Whether scales reduce cutaneous evaporative water loss in lepidosaur reptiles (Superorder Lepidosauria) such as lizards and snakes has been a contentious issue for nearly half a century. Furthermore, while many studies have looked at whether dehydration affects thermal preference in lepidosaurs, far fewer have examined whether normally hydrated lepidosaurs can assess their instantaneous rate of evaporative water loss and adjust their thermal preference to compensate in an adaptive manner. We tested both of these hypotheses using three captive-bred phenotypes of bearded dragon (Pogona vitticeps) sourced from the pet trade: ‘wild-types’ with normal scalation, ‘leatherbacks’ exhibiting scales of reduced prominence, and scaleless bearded dragons referred to as ‘silkbacks’. Silkbacks on average lost water evaporatively at about twice the rate that wild-types did. Leatherbacks on average were closer in their rates of evaporative water loss to silkbacks than they were to wild-types. Additionally, very small (at most ∼1°C) differences in thermal preference existed between the three phenotypes that were not statistically significant. This suggests a lack of plasticity in thermal preference in response to an increase in the rate of evaporative water loss, and may be reflective of a thermal ‘strategy’ as employed by thermoregulating bearded dragons that prioritises immediate thermal benefits over the threat of future dehydration. The results of this study bolster an often-discounted hypothesis regarding the present adaptive function of scales and have implications for the applied fields of animal welfare and conservation.

In vertebrates, changes in surface temperature following exposure to an acute stressor are thought to be promising indicators of the physiological stress response that may be captured noninvasively by infrared thermography. However, the efficacy of using stress‐induced changes in surface temperature as indicators of physiological stress‐responsiveness requires: (1) an understanding of how such responses vary across the body, (2) a magnitude of local, stress‐induced thermal responses that is large enough to discriminate and quantify differences among individuals with conventional technologies, and (3) knowledge of how susceptible measurements across different body regions are to systematic error. In birds, temperature of the bare tissues surrounding the eye (the periorbital, or “eye,” region) and covering the bill have each been speculated as possible predictors of stress physiological state. Using the domestic pigeon (Columba livia domestica; n = 9), we show that stress‐induced changes in surface temperature are most pronounced at the bill and that thermal responses at only the bill have sufficient resolution to detect and quantify differences in responsiveness among individuals. More importantly, we show that surface temperature estimates at the eye region experience greater error due to changes in bird orientation than those at the bill. Such error concealed detection of stress‐induced thermal responses at the eye region. Our results highlight that: (1) in some species, bill temperature may serve as a more robust indicator of autonomic stress‐responsiveness than eye region temperature, and (2) future studies should account for spatial orientation of study individuals if inference is to be drawn from infrared thermographic images., In vertebrates, changes in surface temperature following exposure to an acute stressor are thought to be promising indicators of the physiological stress response that may be captured non‐invasively by infrared thermography. However, the efficacy of using changes in surface temperature as indicators of physiological stress‐responsiveness requires: (1) an understanding of how such responses vary across the body (2) a magnitude of local, stress‐induced thermal responses that is large enough to discriminate and quantify differences among individuals with conventional technologies, and (3) knowledge of how susceptible measurements across different body regions are to systematic error. Using the Domestic Pigeon (Columba livia domestica; n = 9), we show that both the capacity to detect and quantify surface temperature responses to stress‐exposure among individuals depends upon the body region of observation and whether common sources of measurement error (here, individual orientation) are controlled. ​

Plasticity is a reactive mechanism that allows the adaptation of organisms to changing environmental cues. The exploitation of this physiological process has a clear benefit to promote the recovery from a wide range of neurological disorders. Here, we show that plasticity-promoting regimes provide candidate mechanisms to supplement the classically used antidotes for anti-cholinesterase poisoning. These neurotoxins inhibit acetylcholinesterase, causing the overstimulation of cholinergic transmission at synapses and neuromuscular junctions. The model organism C. elegans exhibits organophosphate-induced mitigating plasticity that impacts on the recovery of neuromuscular phenotypes, initially impaired by the drug. This is underpinned by overstimulation of nicotinic receptors at the neuromuscular junction. Intrinsic determinants of receptor’s location and sensitivity modulate the extent of plasticity in the context of persistent cholinergic stimulation. Our results indicate that pharmacological intervention of nicotinic receptors and/or scaffolding proteins that support receptor function might provide a novel treatment route for anti-cholinesterase poisoning.

Human beings are symbolic in the sense that they—uniquely—partition the world into a vocabulary of mental symbols that can be recombined to make statements not only about things as they are, but as they might be. An appraisal of the archaeological and fossil records shows that this unusual way of manipulating information was a recent acquisition, and one that occurred within the tenure of Homo sapiens on the planet. Almost certainly, the necessary neural underpinnings were exaptively acquired along with the distinctive skeletal structure of Homo sapiens, although the new potential was only subsequently released by a necessarily cultural stimulus. This stimulus was most likely the spontaneous and sudden invention of language, the quintessential symbolic activity. That the algorithmic change in brain function involved was more frugal metabolically than its intuitive predecessor is strongly supported by the observed 12.7 percent diminution in average human brain volumes since the late Pleistocene.

Temperate ectotherms have responded to recent environmental change, likely due to the direct and indirect effects of temperature on key life cycle events. Yet, a substantial number of ectotherms are fossorial, spending the vast majority of their lives in subterranean microhabitats that are assumed to be buffered against environmental change. Here, we examine whether seasonal climatic conditions influence body condition (a measure of general health and vigor), reproductive output, and breeding phenology in a northern population of fossorial salamander (Spotted Salamander, Ambystoma maculatum). We found that breeding body condition declined over a 12-year monitoring period (2008-2019) with warmer summer and autumn temperatures at least partly responsible for the observed decline in body condition. Our findings are consistent with the hypothesis that elevated metabolism drives the negative association between temperature and condition. Population-level reproduction, assessed via egg mass counts, showed high interannual variation and was weakly influenced by autumn temperatures. Salamander breeding phenology was strongly correlated with lake ice melt but showed no long-term temporal trend (1986-2019). Climatic warming in the region, which has been and is forecasted to be strongest in the summer and autumn, is predicted to lead to a 5%-27% decline in salamander body condition under realistic near-future climate scenarios. Although the subterranean environment offers a thermal buffer, the observed decline in condition and relatively strong effect of summer temperature on body condition suggest that fossorial salamanders are sensitive to the effects of a warming climate. Given the diversity of fossorial taxa, heightened attention to the vulnerability of subterranean microhabitat refugia and their inhabitants is warranted amid global climatic change.

Complex biological functions within organisms are frequently orchestrated by systemic communication between tissues. In the model organismC. elegans, the pharyngeal and body wall neuromuscular junctions are two discrete structures that control feeding and locomotion, respectively. These distinct tissues are controlled by separate, well-defined neural circuits. Nonetheless, the emergent behaviours, feeding and locomotion, are coordinated to guarantee the efficiency of food intake. We show that pharmacological hyperactivation of cholinergic transmission at the body wall muscle reduces the rate of pumping behaviour. This was evidenced by a systematic screening of the cholinesterase inhibitor aldicarb’s effect on the rate of pharyngeal pumping on food in mutant worms. The screening revealed that the key determinant of the inhibitory effect of aldicarb on pharyngeal pumping is the L-type nicotinic acetylcholine receptor expressed in body wall muscle. This idea was reinforced by the observation that selective hyperstimulation of the body wall muscle L-type receptor by the agonist levamisole inhibited pumping. Overall, our results reveal that body wall cholinergic transmission controls locomotion and simultaneously couples a distal inhibition of feeding.

Background In asthma, IL-6 is a potential cause of enhanced inflammation, tissue damage and airway dysfunction. IL-6 signalling is regulated by its receptor, which is composed of two proteins, IL-6R and GP130. In addition to their membrane form, these two proteins may be found as extracellular soluble forms. The interaction of IL-6 with soluble IL-6R (sIL-6R) can trigger IL-6 trans-signalling in cells lacking IL-6R. Conversely, the soluble form of GP130 (sGP130) competes with its membrane form to inhibit IL-6 trans-signalling. Objectives We aimed to analyse IL-6 trans-signalling proteins in the airways of subjects after an allergen challenge. Methods We used a model of segmental bronchoprovocation with an allergen (SBP-Ag) in human subjects with allergy. Before and 48 h after SBP-Ag, bronchoalveolar lavages (BALs) allowed for the analysis of proteins in BAL fluids (BALFs) by ELISA, and membrane proteins on the surface of BAL cells by flow cytometry. In addition, we performed RNA sequencing (RNA-seq) and used proteomic data to further inform on the expression of the IL-6R subunits by eosinophils, bronchial epithelial cells and lung fibroblasts. Finally, we measured the effect of IL-6 trans-signalling on bronchial fibroblasts, in vitro. Results IL-6, sIL-6R, sGP130 and the molar ratio of sIL-6R/sGP130 increased in the airways after SBP-Ag, suggesting the potential for enhanced IL-6 trans-signalling activity. BAL lymphocytes, monocytes and eosinophils displayed IL-6R on their surface and were all possible providers of sIL-6R, whereas GP130 was highly expressed in bronchial epithelial cells and lung fibroblasts. Finally, bronchial fibroblasts activated by IL-6 trans-signalling produced enhanced amounts of the chemokine, MCP-1 (CCL2). Conclusion and clinical relevance After a bronchial allergen challenge, we found augmentation of the elements of IL-6 trans-signalling. Allergen-induced IL-6 trans-signalling activity can activate fibroblasts to produce chemokines that can further enhance inflammation and lung dysfunction.

BackgroundColitis is one of the common immune-related adverse events that leads to morbidity and treatment discontinuation of immunotherapy. The clinical presentation, endoscopic and histopathological features and best management of this toxicity are not well defined.Patients and methodsPatients with metastatic melanoma who received immunotherapy (programmed cell death protein 1 (PD1) antibodies, alone or in combination with a cytotoxic T-lymphocyte-associated protein 4 (CTLA-4) antibody (PD1 +CTLA-4)) and who developed clinically significant colitis (requiring systemic corticosteroids) were identified retrospectively from two academic centers. Clinical data were collected for all patients; endoscopic and histopathological data were examined in a subset.ResultsFrom May 2013 to May 2019, 118/1507 (7.8%) patients developed significant colitis; 80/553 (14.5%) after PD1+CTLA-4, 35/1000 (3.5%) PD1 alone, and three patients after Ipilimumab (IPI) alone. Combination therapy-induced colitis was more frequent (14.5% vs 3.5% in PD1 alone, p=ConclusionClinically significant colitis varies in presentation, response to immunosuppression, and endoscopic/histologic features depending on the immunotherapy type. Infliximab-refractory colitis occurs early, is often high grade, and has adverse endoscopic and histopathologic features

Behavioural flexibility allows ectotherms to exploit the environment to govern their metabolic physiology, including in response to environmental stress. Hydrogen sulfide (H 2 S) is a widespread environmental toxin that can lethally inhibit metabolism. However, H 2 S can also alter behaviour and physiology, including a hypothesized induction of hibernation-like states characterized by downward shifts of the innate thermal set point (anapyrexia). Support for this hypothesis has proved controversial because it is difficult to isolate active and passive components of thermoregulation, especially in animals with high resting metabolic heat production. Here, we directly test this hypothesis by leveraging the natural behavioural thermoregulatory drive of fish to move between environments of different temperatures in accordance with their current physiological state and thermal preference. We observed a decrease in adult zebrafish ( Danio rerio ) preferred body temperature with exposure to 0.02% H 2 S, which we interpret as a shift in the thermal set point. Individuals exhibited consistent differences in shuttling behaviour and preferred temperatures, which were reduced by a constant temperature magnitude during H 2 S exposure. Seeking lower temperatures alleviated H 2 S-induced metabolic stress, as measured by reduced rates of aquatic surface respiration. Our findings highlight the interactions between individual variation and sublethal impacts of environmental toxins on behaviour.

The genetic basis for the emergence of creativity in modern humans remains a mystery despite sequencing the genomes of chimpanzees and Neanderthals, our closest hominid relatives. Data-driven methods allowed us to uncover networks of genes distinguishing the three major systems of modern human personality and adaptability: emotional reactivity, self-control, and self-awareness. Now we have identified which of these genes are present in chimpanzees and Neanderthals. We replicated our findings in separate analyses of three high-coverage genomes of Neanderthals. We found that Neanderthals had nearly the same genes for emotional reactivity as chimpanzees, and they were intermediate between modern humans and chimpanzees in their numbers of genes for both self-control and self-awareness. 95% of the 267 genes we found only in modern humans were not protein-coding, including many long-non-coding RNAs in the self-awareness network. These genes may have arisen by positive selection for the characteristics of human well-being and behavioral modernity, including creativity, prosocial behavior, and healthy longevity. The genes that cluster in association with those found only in modern humans are over-expressed in brain regions involved in human self-awareness and creativity, including late-myelinating and phylogenetically recent regions of neocortex for autobiographical memory in frontal, parietal, and temporal regions, as well as related components of cortico-thalamo-ponto-cerebellar-cortical and cortico-striato-cortical loops. We conclude that modern humans have more than 200 unique non-protein-coding genes regulating co-expression of many more proteincoding genes in coordinated networks that underlie their capacities for self-awareness, creativity, prosocial behavior, and healthy longevity, which are not found in chimpanzees or Neanderthals.

Inhibition of acetylcholinesterase by either organophosphates or carbamates causes anti-cholinesterase poisoning. This arises through a wide range of neurotoxic effects triggered by the overstimulation of the cholinergic receptors at synapses and neuromuscular junctions. Without intervention, this poisoning can lead to profound toxic effects, including death, and the incomplete efficacy of the current treatments, particularly for oxime-insensitive agents, provokes the need to find better antidotes. Here we show how the non-parasitic nematodeCaenorhabditis elegansoffers an excellent tool for investigating the acetylcholinesterase intoxication. TheC. elegansneuromuscular junctions show a high degree of molecular and functional conservation with the cholinergic transmission that operates in the autonomic, central and neuromuscular synapses in mammals. In fact, the anti-cholinesterase intoxication of the worm’s body wall neuromuscular junction has been unprecedented in understanding molecular determinants of cholinergic function in nematodes and other organisms. We extend the use of the model organism’s feeding behaviour as a tool to investigate carbamate and organophosphate mode of action. We show that inhibition of the cholinergic-dependent rhythmic pumping of the pharyngeal muscle correlates with the inhibition of the acetylcholinesterase activity caused by aldicarb, paraoxons and DFP exposure. Further, this bio-assay allows one to address oxime dependent reversal of cholinesterase inhibition in the context of whole organism recovery. Interestingly, the recovery of the pharyngeal function after such anti-cholinesterase poisoning represents a sensitive and easily quantifiable phenotype that is indicative of the spontaneous recovery or irreversible modification of the worm acetylcholinesterase after inhibition. These observations highlight the pharynx ofC. elegansas a new tractable approach to explore anti-cholinesterase intoxication and recovery with the potential to resolve critical genetic determinants of these neurotoxins’ mode of action.

Purpose To examine the effects of different sources of social support (team vs. family/friends) during recovery from injury on post-injury depression and anxiety symptoms among college student-athletes. Methods College student-athletes from two Big 10 universities were prospectively enrolled at the beginning of the 2007–2008 through 2011–2012 sport seasons and followed for injury. Depression and anxiety scores were assessed at baseline and at multiple time points post-injury until return-to-play. Linear mixed models were used to examine the effects of social support from family/friends or from the team (coaches, athletic trainers, and teammates) during recovery, along with satisfaction with the support received, on changes in post-injury depression and anxiety scores. Results A total of 597 injuries (sustained by 397 athletes) were included in the analysis. Of these injuries, 67% occurred in males, 39.9% occurred during football, and 11.9% were concussions. Average depression and anxiety scores at baseline were 10.7 and 41.3, respectively. Results showed that the quantity of social support received from family/friends during recovery significantly influenced post-injury depression scores (β=0.60, p=0.028). No such relationship was found between social support received from the team and depression scores. Furthermore, overall satisfaction with social support received during recovery, regardless of the source of social support, was negatively associated with post-injury scores in depression (p Conclusion College student-athletes’ satisfaction with the social support received from both family/friends and one’s team post-injury was negatively associated with post-injury depression and anxiety scores. Although family/friends are often a major source of social support post-injury, future efforts are needed to increase social support from one’s team, which in turn may help mitigate the risk of depression and anxiety post-injury. Significance Social support from family/friends or one’s team post-injury may help college student-athletes cope with the psychological impact of injury, reducing post-injury depression and anxiety symptoms.

Quorum‐sensing mechanisms regulate gene expression in response to changing cell‐population density detected through pheromones. In Enterococcus faecalis, Fsr quorum sensing produces and responds to the gelatinase biosynthesis‐activating pheromone (GBAP). Here we establish that the enterococcal FsrB membrane protein has a direct role connected with GBAP by showing that GBAP binds to purified FsrB. Far‐UV CD measurements demonstrated a predominantly α‐helical protein exhibiting a small level of conformational flexibility. Fivefold (400 μm) GBAP stabilised FsrB (80 μm) secondary structure. FsrB thermal denaturation in the presence and absence of GBAP revealed melting temperatures of 70.1 and 60.8 °C, respectively, demonstrating GBAP interactions and increased thermal stability conferred by GBAP. Addition of GBAP also resulted in tertiary structural changes, confirming GBAP binding.

Made available in DSpace on 2020-12-12T01:37:17Z (GMT). No. of bitstreams: 0 Previous issue date: 2020-01-01 Recent discoveries of stone tools from Jordan (2.5 Ma) and China (2.1 Ma) document hominin presence in Asia at the beginning of the Pleistocene, well before the conventional Dmanisi datum at 1.8 Ma. Although no fossil hominins documenting this earliest Out of Africa phase have been found, on chronological grounds a pre-Homo erectus hominin must be considered the most likely maker of those artifacts. If so, this sheds new light on at least two disputed subjects in paleoanthropology, namely the remarkable variation among the five Dmanisi skulls, and the ancestry of Homo floresiensis. Universidade Estadual Paulista (UNESP) Instituto de Geociências e Ciências Exatas Universidade de São Paulo (USP) Instituto de Estudos Avançados Division of Anthropology American Museum of Natural History Universidade Estadual Paulista (UNESP) Instituto de Geociências e Ciências Exatas

Global trends in the demand for forest products, decreasing total area of actively managed forests, and pressures to increase profit margins suggest that forest management intensity will continue to increase in the future. These trends have typically led to shorter rotation lengths and increased utilization of forest biomass to supply the bio-economy with feedstocks for energy, novel bio-chemicals, traditional pulp and paper, panels and solid forest products. The combined influence of increased utilization and shortened rotation lengths have raised concerns regarding potential soil nutrient depletion and corresponding reductions in site productivity. In response to these concerns, the Weymouth Point Study Area (WPSA) in north-central Maine was established in a spruce-fir forest in 1979 to quantify the effects of whole-tree harvesting (WTH) and stem-only harvesting (SOH) on nutrient cycling and site productivity in adjacent, paired watersheds with large fixed-area plots. From 1979 to 2016, 49 permanent sample plots were established across three soil drainage classes to evaluate tree- and stand-level growth and nutrition response to harvest residue management and silviculture practices. Harvest treatments were implemented in 1981 with SOH simulated by returning delimbing residues after WTH, including chipped tops, branches and foliage (CHP), and lopped-and-scattered residues (LOP). The harvested watershed was aerially treated with triclopyr herbicide in the fourth growing season following WTH to release naturally regenerated conifers from herbaceous and woody weed competition. Response to silviculture practices were evaluated following pre-commercial thinning (PCT) and the addition of ammonium-nitrate fertilizer (FERT) treatments initiated 10 and 12 years following WTH, respectively. Thirty-five years post-harvest, tree growth and nutrient uptake have not been significantly affected by WTH at this location. Mean tree size was positively influenced by PCT; however, FERT did not significantly affect mean tree size. There were also no significant effects of treatments on aboveground biomass production and net nutrient uptake in trees. These results suggest that WTH at final felling for bio-economy feedstock production in spruce-fir forests similar to those at the WPSA (Chesuncook catena soils) is sustainable. However, this hypothesis is based on mid-rotation assessment of tree growth as an indicator of sustainable forest management. Further research is required to confirm the absence of negative impacts on tree- and stand-level growth and nutrition through the end of the current rotation.

BACKGROUND: Inflammation is intimately involved in the pathogenesis of atherosclerosis and is accurately measured by high sensitivity C-reactive protein (hs-CRP), a sensitive marker for future risk of cardiovascular disease. The Correlation between Oral Health and Systemic Inflammation (COHESION) trial was designed to test the hypothesis that PlaqueHD, a plaque identifying toothpaste, reduces hs-CRP. METHODS: COHESION was designed initially to enroll 132 subjects with hs-CRP between 2.0 and 10.0 milligrams per liter but randomized 112 between 0.5 and 10.0, of which 103 had baseline and follow up data and comprise the intention to treat sample. Of these, a pre-specified subgroup analysis included 40 with baseline hs-CRP > 2.0 and all hs-CRP < 10. Since the distribution of hs-CRP was skewed toward higher values, to achieve normality assumptions, the significance of changes in hs-CRP between groups over time was tested on log-transformed data using a mixed effects analysis of variance. RESULTS: The intention-to-treat analysis showed no significant differences between the PlaqueHD and placebo group (p=0.615). The pre-specified subgroup analysis showed a significant difference between the PlaqueHD and placebo group (p=0.047). This finding resulted from a reduction in hs-CRP at follow up of 0.58 in the PlaqueHD and an increase of 0.55 in the placebo group. CONCLUSIONS: These findings are compatible with those of a prior pilot trial which also suggested benefits only in subjects with baseline elevations. These findings suggest that future trials targeting reductions of hs-CRP levels should randomize subjects with baseline hs-CRP between 2.0 and 10.0.

[Figure][1] Glenn Tattersall and Warren Burggren discuss the impact of Robert Boutilier and Graham Shelton’s classic 1986 JEB paper ‘Gas exchange, storage and transport in voluntarily diving Xenopus laevis ’. Robert ‘Bob’ Boutilier was a deep and philosophical thinker and an

Summary 1.Darwin's finches have been the focus of intense study demonstrating how climatic fluctuations coupled with resource competition drive the evolution of a variety of bill sizes and shapes. The bill, as other peripheral surfaces, also plays an important role in thermoregulation in numerous bird species. The avian bill is vascularized, while limbs have specialized vasculature that facilitate heat loss or heat conservation (i.e., they are thermoregulatory windows). 2.The Galapagos Islands, home to Darwin's finches, have a hot and relatively dry climate for approximately half of the year, during which thermoregulatory windows (i.e. surfaces) could be important for thermoregulation and the linked challenge of water balance. 3.We hypothesized that Darwin's finch bills have evolved in part for their role in thermoregulation, possibly co-opted, following adaptation for other functions, such as foraging. We predicted that bills of Darwin's finches are effective thermoregulatory windows, and that species differences in bill morphology, along with physiology and behavior, lead to differences in thermoregulatory function. 4.To test these hypotheses, we conducted a field study to assess heat exchange and microclimate use in three ground finch species and sympatric cactus finch (Geospiza spp.). We collected thermal images of free-living birds during a hot and dry season and recorded microclimate data for each observation. We used individual thermographic data to model the contribution of bills, legs, and bodies to overall heat balance and compared surface temperatures to those from dead birds to test physiological control of heat loss from these surfaces. We derived and compared species-specific threshold environmental temperatures, which are indicative of a species’ thermally neutral temperature. 5.In all species, the bill surface was an effective heat dissipater during naturally occurring warm temperatures. As expected, we found that finches controlled surface temperatures through physiology and that young birds had higher surface temperatures than adults. Larger bills contributed proportionally more to overall heat loss than smaller bills. 6.We demonstrate here that related, sympatric species with different bill sizes exhibit different patterns in the use of these thermoregulatory structures, supporting a role for thermoregulation in the evolution and ecology of Darwin's finch morphology. This article is protected by copyright. All rights reserved.

In minute virus of mice (MVM) capsids, icosahedral five-fold channels serve as portals mediating genome packaging, genome release, and the phased extrusion of viral peptides. Previous studies suggest that residues L172 and V40 are essential for channel function. The structures of MVMi wildtype, and mutant L172T and V40A virus-like particles (VLPs) were solved from cryo-EM data. Two constriction points, termed the mid-gate and inner-gate, were observed in the channels of wildtype particles, involving residues L172 and V40 respectively. While the mid-gate of V40A VLPs appeared normal, in L172T adjacent channel walls were altered, and in both mutants there was major disruption of the inner-gate, demonstrating that direct L172:V40 bonding is essential for its structural integrity. In wildtype particles, residues from the N-termini of VP2 map into claw-like densities positioned below the channel opening, which become disordered in the mutants, implicating both L172 and V40 in the organization of VP2 N-termini.

We describe the first reported hybrid to occur in nature between Dactylorhiza praetermissa and Gymnadenia borealis as × Dactylodenia lacerta R.M. Bateman & Tattersall. This vigorous plant was found...

The protoparvovirus early promoters, e.g. P4 of Minute Virus of Mice (MVM), play a critical role during infection. Initial P4 activity depends on the host transcription machinery only. Since this is cell-type dependent, it is hypothesized that P4 is a host cell-type range determinant. Yet host range determinants have mapped mostly to capsid, never P4. Here we test the hypothesis using the mouse embryo as a model system. Disruption of the CRE element of P4 drastically decreased infection levels without altering range. However, when we swapped promoter elements of MVM P4 with those from equivalent regions of the closely related H1 virus, we observed elimination of infection in fibroblasts and chondrocytes and the acquisition of infection in skeletal muscle. We conclude that P4 is a host range determinant and a target for modifying the productive infection potential of the virus - an important consideration in adapting these viruses for oncotherapy.

Climate change and global wood products demand raise concerns about boreal forest ecosystem resilience to natural disturbances and harvesting. A chronosequence experiment located in Foret Montmorency, Quebec was used to evaluate the effects of harvesting on carbon (C) recovery trajectories at the stand level over a period of 77 years in balsam fir-white birch stands. Empirical estimates of 19 Foret Montmorency forest carbon pools were compared with those simulated by the Carbon Budget Model (CBM-CFS3) to test model assumptions for predicting carbon dynamics in this forest. The model was initialized using forest inventory data, spatially explicit environmental conditions, and disturbance matrices designed to represent historical spruce budworm epidemics in Foret Montmorency. Over the chronosequence, total ecosystem C increased significantly (p = 0.05) following harvest from 211 Mg in year-zero to 279 ± 8 Mg C ha⁻¹ in year 67 (mean ± SE), suggesting that FM carbon pools were recovering to pre-harvest levels after seven decades. The CBM-CFS3 model predicted total ecosystem C stocks within 10% of the empirical mean at stand maturity; however, several predicted C pools deviated from field observations in both C amounts and trends over time. The greatest differences were in deadwood and soil C pools, suggesting that model initialization of dead organic matter pools did not adequately simulate the 1000-yr history of C-pool transfers and stand dynamics leading up to the harvest. Modifications to CBM-CFS3 initialization assumptions and default decay parameters may more accurately simulate long-term effects of natural disturbances on C pools for this forest region.

Background Haemophagocytic lymphohistiocytosis (HLH)/macrophage activation syndrome (MAS) is a hyperinflammatory syndrome potentially leading to critical illness. Early treatment reduces mortality but diagnosis requires a high index of suspicion. Highly elevated ferritin levels (HEF) >10,000 μg/L are highly specific for HLH/MAS [1] and should prompt consideration of hyperinflammation. Diagnostic guidelines for HLH, requiring the presence of ≥5/8 criteria [2], and classification criteria for MAS complicating systemic juvenile idiopathic arthritis (sJIA) have been published [3]. Objectives To assess recognition of HLH/MAS in a paediatric population with HEF. Methods This retrospective study was conducted at 11 centres under local service evaluation permissions. Biochemistry databases identified patients ≤16 years with serum ferritin >10,000 μg/L during a 3-year period. Each case was assessed against the 2004 HLH criteria and, for patients with sJIA, the 2016 MAS criteria. Due to limited access to some of the laboratory tests, previously-published modified HLH criteria using a threshold of ≥4/5 (excluding tissue haemophagocytosis, decreased natural killer cell function, increased soluble interleukin-2 receptor) were also applied to all patients [4]. Results 153 patients (55.6% male) were identified. Patient diagnoses included: infections (29.4%), rheumatological (17.0%) and malignancies (17.0%). A diagnosis of HLH/MAS was made by the treating clinical team in 39.9% and considered in a further 16.3%. Using all available data, 30/153 (19.6%) met ≥5/8 criteria and 93.3% of these patients were diagnosed with HLH/MAS by the treating team. 56 (36.6%) met ≥4/5 criteria and 33 (58.9%) of these were diagnosed with HLH/MAS by clinicians. HLH/MAS was not documented as being considered in the differential in 23.2%. Of 23 patients with sJIA, 82.6% met MAS classification criteria and 89.5% of these were diagnosed with MAS by the treating clinicians. Overall mortality was 32.7% (50/153) and was 27.9% (17/61) in patients diagnosed with HLH/MAS during their admission. Conclusion Although HEF is highly specific for HLH/MAS, the diagnosis was only made or considered in just over half of paediatric patients with this laboratory result. Increased awareness of this potentially-lethal condition is likely to lead to earlier treatment and reduced mortality. References [1] Allen CE, et al. 2008;50:1227-35. [2] Henter JI, et al. 2007;48:124-31. [3] Ravelli A, et al. 2016;75:481-9. [4] Davi S, et al. 2014;66:2871-80. Disclosure of Interests Ethan Sen: None declared, Beverley Almeida: None declared, Louise Moran: None declared, Charlene Foley: None declared, Nagla Abdelrahman: None declared, Rosie Close: None declared, Ema-Louise Long: None declared, Joshua Bennett: None declared, Jason Palman: None declared, Catriona Anderson: None declared, Kirsty McLellan: None declared, Samundeeswari Deepak: None declared, Kathy Gallagher: None declared, Peter Bale: None declared, Kamran Mahmood: None declared, Clare Pain: None declared, Flora McErlane: None declared, Athimalaipet Ramanan Consultant for: AbbVie, UCB, Sobi, Eli Lilly, Speakers bureau: Speaker fees/honoraria from Abbvie, SOBI, Eli Lilly and UCB, Speakers bureau: AbbVie, UCB, Sobi, Eli Lilly, Rachel Tattersall: None declared

Background Not all rhinitis patients are affected by an immunoglobulin E (IgE)-mediated inflammatory process. Skin and serum allergy assessments are limited in their ability to define local allergic rhinitis (LAR). Thus, patients with negative systemic allergy assessments comprise a mix of those who truly have nonallergic rhinitis (NAR) and patients with LAR. Objective To determine the clinical characteristics of patients with NAR. Methods A cross-sectional study was performed on consecutive adults with rhinitis symptoms who underwent turbinate surgery. NAR patients were defined by excluding allergy using both systemic (serum-specific IgE and/or skin prick test) and local (inferior turbinate tissue-specific IgE) tests. Allergic rhinitis (AR) patients were defined by any positive systemic or local test toward aeroallergens. The clinical characteristics studied included allergic comorbidities (asthma, eczema, allergic conjunctivitis), inhalant allergen triggers (dust, pollen, animal dander), and environmental triggers (Cincinnati Irritant Index [CII]). Results There were 154 participants (41.79 ± 14.78 years, 37.7% female). NAR patients (11.7%) were older (49.33 ± 15.99 vs 40.78 ± 14.38 years, P = .02), had less self-reported asthma (5.6% vs 36.3%, P Conclusion Patients who were older, without asthma, and lacked an inhalant allergy trigger were more likely to have true NAR. Environmental triggers are not distinguishing features of NAR. This may be used as a guide to identify rhinitis patients whose symptoms are truly nonallergic etiology compared to those with falsely negative systemic allergy assessment but may still need management for LAR.

Objective— Lp(a) [lipoprotein(a)] is a well-described risk factor for atherosclerosis, but Lp(a)-associated risk may vary by race/ethnicity. We aimed to determine whether race/ethnicity modifies Lp(a)-related risk of carotid atherosclerotic plaque outcomes among black, white, Chinese, and Hispanic individuals. Approach and Results— Carotid plaque presence and score were assessed by ultrasonography at baseline (n=5155) and following a median 9.4 year period (n=3380) in MESA (Multi-Ethnic Study of Atherosclerosis) participants. Lp(a) concentrations were measured by immunoassay and examined as a continuous and categorical variable using clinically-based cutoffs, 30 and 50 mg/dL. Lp(a) was related to greater risk of prevalent carotid plaque at baseline in whites alone (all P P P =0.04). In prospective analyses, whites with Lp(a) ≥50 mg/dL were found to have greater risk of plaque progression (relative risk, 1.12; P =0.03) and higher plaque scores (all P Conclusions— Race was found to be a modifying variable in Lp(a)-related risk of carotid plaque, and Lp(a) levels may have greater influence on plaque burden in whites than in black individuals. Borderline results in Hispanics suggest that elevated Lp(a) may increase the risk of carotid plaque, but follow-up studies are needed.

We discovered a previously undescribed orbital lipid depot in the thirteen-lined ground squirrel during the first ever magnetic resonance image (MRI) of this common experimental model of mammalian hibernation. In animals housed at constant ambient temperatures (5°C or 25°C, 12 h:12 h light:dark photoperiod), the volume of this depot increased in the autumn and decreased in the spring, suggesting an endogenous circannual pattern. Water-fat MRI revealed that throughout the year this depot is composed of ∼40% lipid, similar to brown adipose tissue (BAT). During arousal from torpor, thermal images showed higher surface temperatures near this depot before the rest of the head warmed, suggesting a thermoregulatory function. This depot, however, does not contain uncoupling protein 1, a BAT biomarker, or uncoupling protein 3. Histology shows blood vessels in close proximity to each other, suggesting it may serve as a vascular rete, perhaps to preferentially warm the eye and brain during arousals.

The avian bill is a textbook example of how evolution shapes morphology in response to changing environments. Bills of seed-specialist finches in particular have been the focus of intense study demonstrating how climatic fluctuations acting on food availability drive bill size and shape. The avian bill also plays an important but under-appreciated role in body temperature regulation, and therefore in energetics. Birds are endothermic and rely on numerous mechanisms for balancing internal heat production with biophysical constraints of the environment. The bill is highly vascularised and heat exchange with the environment can vary substantially, ranging from around 2% to as high as 400% of basal heat production in certain species. This heat exchange may impact how birds respond to heat stress, substitute for evaporative water loss at elevated temperatures or environments of altered water availability, or be an energetic liability at low environmental temperatures. As a result, in numerous taxa, there is evidence for a positive association between bill size and environmental temperatures, both within and among species. Therefore, bill size is both developmentally flexible and evolutionarily adaptive in response to temperature. Understanding the evolution of variation in bill size however, requires explanations of all potential mechanisms. The purpose of this review, therefore, is to promote a greater understanding of the role of temperature on shaping bill size over spatial gradients as well as developmental, seasonal, and evolutionary timescales.

Objective— Plasma high-density lipoproteins have several putative antiatherogenic effects, including preservation of endothelial functions. This is thought to be mediated, in part, by the ability of high-density lipoproteins to promote cholesterol efflux from endothelial cells (ECs). The ATP-binding cassette transporters A1 and G1 (ABCA1 and ABCG1) interact with high-density lipoproteins to promote cholesterol efflux from ECs. To determine the impact of endothelial cholesterol efflux pathways on atherogenesis, we prepared mice with endothelium-specific knockout of Abca1 and Abcg1 . Approach and Results— Generation of mice with EC-ABCA1 and ABCG1 deficiency required crossbreeding Abca1 fl/fl Abcg1 fl/fl Ldlr −/− mice with the Tie2Cre strain, followed by irradiation and transplantation of Abca1 fl/fl Abcg1 fl/fl bone marrow to abrogate the effects of macrophage ABCA1 and ABCG1 deficiency induced by Tie2Cre. After 20 to 22 weeks of Western-type diet, both single EC- Abca1 and Abcg1 deficiency increased atherosclerosis in the aortic root and whole aorta. Combined EC- Abca1/g1 deficiency caused a significant further increase in lesion area at both sites. EC- Abca1/g1 deficiency dramatically enhanced macrophage lipid accumulation in the branches of the aorta that are exposed to disturbed blood flow, decreased aortic endothelial NO synthase activity, and increased monocyte infiltration into the atherosclerotic plaque. Abca1/g1 deficiency enhanced lipopolysaccharide-induced inflammatory gene expression in mouse aortic ECs, which was recapitulated by ABCG1 deficiency in human aortic ECs. Conclusions— These studies provide direct evidence that endothelial cholesterol efflux pathways mediated by ABCA1 and ABCG1 are nonredundant and atheroprotective, reflecting preservation of endothelial NO synthase activity and suppression of endothelial inflammation, especially in regions of disturbed arterial blood flow.

Because of the greater morphological distances among them, genera should be more robustly recognizable in the fossil record than species are. But there are clearly upper as well as lower bounds to their species inclusivity. Currently, the vast majority of fossils composing the large and rapidly expanding paleoanthropological record are crammed into one of two genera (Australopithecus vs Homo), expanding the latter, especially, far beyond any reasonable morphological or phylogenetic limits. This excessive inclusivity obscures both diversity and the complexities of phylogenetic structure within the hominid family.

Temperate snakes occupy overwintering sites for most of their annual life cycle. Microhabitat characteristics of the hibernaculum are largely undescribed, yet are paramount in ensuring snake overwintering survival. We hypothesized that snakes survive hibernation within a vertical subterranean space that we termed a “life zone” (LZ), that is aerobic and flood and frost free throughout winter. We studied an isolated, endangered population of Massasaugas (Sistrurus catenatus) inhabiting an anthropogenically altered peatland and monitored the subterranean habitat during a period of environmental stochasticity. Initial radio telemetry confirmed that snakes moved between altered and natural habitats during the active season and showed hibernation-site fidelity to either habitat. We used a grid of groundwater wells and frost tubes installed in each hibernation area to measure LZ characteristics over 11 consecutive winters. The LZ within the impacted area was periodically reduced to zero during a flood–freeze cycle, but the LZ in the natural area was maintained. Model selection analysis revealed that soil depth and flood status best predicted LZ size. Thermal buffering and groundwater dissolved oxygen increased with LZ size, and annual Massasauga encounters were significantly correlated with LZ size. This analysis suggests a population decline occurred when LZ size was reduced by flooding. Our data give support to the importance and maintenance of an LZ for successful snake hibernation. Our methods apply to subterranean hibernation habitats that are at risk of environmental stochasticity, causing flooding, freezing, or hypoxia.