Plasma Inclusive Resuscitation Is Not Associated With Coagulation Profile Changes in Burn Patients.

INTRODUCTION: Dynamically titrated crystalloids are the standard of care for burn shock resuscitation. There are theoretical concerns that the adjunctive use of allogeneic plasma may perturb the patient's coagulation and inflammation status deleteriously. It was hypothesized that plasma-inclusive resuscitation (PIR) would not be associated with prothrombotic changes relative to baseline after thermal injury. METHODS: Patients admitted to a regional burn center who were treated with PIR as part of their burn resuscitation were enrolled. Whole blood samples were analyzed prospectively via rapid thromboelastography and rotational thromboelastometry to assess for coagulopathy at four time points throughout their acute burn resuscitation. The mixed-effect model for repeated measures followed by Tukey's post hoc test for comparisons was used to examine group differences. RESULTS: There were 35 patients in the analysis. Most were male (74.3%) with a median age of 43 y (32-55), concomitant inhalation injury of 28.6%, total body surface area burn size of 34% (27%-48.5%), and the overall mortality of the cohort was 28.6%. There were no transfusion reactions or thrombotic events. There were no differences in thromboelastography or rotational thromboelastometry parameters overall or when stratified by mortality, total body surface area burn, and inhalation injury. There were no significant differences between the fibrinolytic phenotypes over time. CONCLUSIONS: Data suggest that PIR was not associated with prothrombotic or lytic changes in burn patients relative to baseline. Further research is needed to confirm these findings and evaluate efficacy of PIR in acute burn resuscitation.

The neurotrophic factor MANF regulates autophagy and lysosome function to promote proteostasis in Caenorhabditis elegans.

The conserved mesencephalic astrocyte-derived neurotrophic factor (MANF) is known for protecting dopaminergic neurons and functioning in various other tissues. Previously, we showed that Caenorhabditis elegans manf-1 null mutants exhibit defects such as increased endoplasmic reticulum (ER) stress, dopaminergic neurodegeneration, and abnormal protein aggregation. These findings suggest an essential role for MANF in cellular processes. However, the mechanisms by which intracellular and extracellular MANF regulate broader cellular functions remain unclear. We report a unique mechanism of action for MANF-1 that involves the transcription factor HLH-30/TFEB-mediated signaling to regulate autophagy and lysosomal function. Multiple transgenic strains overexpressing MANF-1 showed extended lifespan of animals, reduced protein aggregation, and improved neuronal survival. Using fluorescently tagged MANF-1, we observed tissue-specific localization of the protein, which was dependent on the ER retention signal. Further subcellular analysis showed that MANF-1 localizes within cells to the lysosomes and utilizes the endosomal pathway. Consistent with the lysosomal localization, our transcriptomic study of MANF-1 and analyses of autophagy regulators demonstrated that MANF-1 promotes proteostasis by regulating autophagic flux and lysosomal activity. Collectively, our findings establish MANF as a critical regulator of stress response, proteostasis, and aging.

Reduced voluntary wheel running behaviour in Kiss1r knockout mice.

Kisspeptin and its receptor, Kiss1r, are novel players in the central balance of energy intake and expenditure. Recent evidence also indicates that kisspeptin signalling is important in thermoregulation and generation of the circadian rhythm. We used global Kiss1r knockout mice (Kiss1r KO), which are hypogonadal and develop obesity, to determine the impact of kisspeptin on circadian related behaviour. Voluntary wheel running was examined in Kiss1r KO and wild-type (WT) mice, using gonad intact and gonadectomised (GDX) mice to account for the effects of kisspeptin on gonadal sex steroids. Intact male and female Kiss1r KO mice covered only 10% and 30% of the distance travelled each day by their respective WT controls. In all mice, most of the running activity occurred during the dark phase. GDX WT mice ran significantly less during dark periods than the intact WT. GDX Kiss1r KO male mice ran significantly less than the GDX WT male mice, but the decrease was attenuated compared to intact mice. There was no difference between the female GDX Kiss1r KO and GDX WT. In contrast to the obese phenotype that develops in Kiss1r KO mice, body mass at the end of the study was significantly lower in the GDX Kiss1r KO than it was in the GDX WT mice. The difference in wheel running activity was not associated with any histological change in WAT, BAT, or muscle diameter. No difference in immunohistochemistry expression was seen in lateral hypothalamic orexin neurons or dopamine neurons in the ventral tegmental area / substantia nigra. We observed increased Iba1 expression (activation of microglia) in the arcuate nucleus of male Kiss1r KO mice. Overall, the circadian locomotor activity in male Kiss1r KO mice appears dependant on kisspeptin signalling and the obese phenotype does not develop in Kiss1r KO mice when they engage in voluntary activity.

Robust control of electrohydraulic soft robots.

This article introduces a model-based robust control framework for electrohydraulic soft robots. The methods presented herein exploit linear system control theory as it applies to a nonlinear soft robotic system. We employ dynamic mode decomposition with control (DMDc) to create appropriate linear models from real-world measurements. We build on the theory by developing linear models in various operational regions of the system to result in a collection of linear plants used in uncertainty analysis. To complement the uncertainty analyses, we utilize H ∞ ("H Infinity") synthesis techniques to determine an optimal controller to meet performance requirements for the nominal plant. Following this methodology, we demonstrate robust control over a multi-input multi-output (MIMO) hydraulically amplified self-healing electrostatic (HASEL)-actuated system. The simplifications in the proposed framework help address the inherent uncertainties and complexities of compliant robots, providing a flexible approach for real-time control of soft robotic systems in real-world applications.

Measurement of microclimates in a warming world: problems and solutions.

As the world warms, it will be tempting to relate the biological responses of terrestrial animals to air temperature. But air temperature typically plays a lesser role in the heat exchange of those animals than does radiant heat. Under radiant load, animals can gain heat even when body surface temperature exceeds air temperature. However, animals can buffer the impacts of radiant heat exposure: burrows and other refuges may block solar radiant heat fully, but trees and agricultural shelters provide only partial relief. For animals that can do so effectively, evaporative cooling will be used to dissipate body heat. Evaporative cooling is dependent directly on the water vapour pressure difference between the body surface and immediate surroundings, but only indirectly on relative humidity. High relative humidity at high air temperature implies a high water vapour pressure, but evaporation into air with 100% relative humidity is not impossible. Evaporation is enhanced by wind, but the wind speed reported by meteorological services is not that experienced by animals; instead, the wind, air temperature, humidity and radiation experienced is that of the animal's microclimate. In this Commentary, we discuss how microclimate should be quantified to ensure accurate assessment of an animal's thermal environment. We propose that the microclimate metric of dry heat load to which the biological responses of animals should be related is black-globe temperature measured on or near the animal, and not air temperature. Finally, when analysing those responses, the metric of humidity should be water vapour pressure, not relative humidity.

Living in Western Australia induces some physiological adaptations of seasonal acclimatisation in the surgical burns team.

Seasonal acclimatization is known to result in adaptations that can improve heat tolerance. Staff who operate on burn injuries are exposed to thermally stressful conditions and seasonal acclimatization may improve their thermoeffector responses during surgery. Therefore, the aim of this study was to assess the physiological and perceptual responses of staff who operate on burn injuries during summer and winter, to determine whether they become acclimatized to the heated operating theater. Eight staff members had physiological and perceptual responses compared during burn surgeries conducted in thermoneutral (CON: 24.1 ± 1.2°C, 45 ± 7% relative humidity [RH]) and heated (HOT: 31.3 ± 1.6°C, 44 ± 7% RH) operating theaters, in summer and winter. Physiological parameters that were assessed included core temperature, heart rate, total sweat loss, sweat rate, and urinary specific gravity. Perceptual responses included ratings of thermal sensation and comfort. In summer, CON compared to winter CON, baseline (85 ± 15 bpm VS 94 ± 18 bpm), mean (84 ± 16 bpm VS 93 ± 18 bpm), and peak HR (94 ± 17 bpm VS 105 ± 19 bpm) were lower (p < 0.05), whereas core temperature was not different between seasons in either condition (p > 0.05). In HOT, ratings of discomfort were higher in summer (15 ± 3) than winter (13 ± 3; p > 0.05), but ratings of thermal sensation and sweat rate were similar between seasons (p > 0.05). The surgical team in burns in Western Australia can obtain some of the physiological adaptations that result from seasonal acclimatization, but not all. That is most likely due to a lower than required amount of outdoor heat exposure in summer, to induce all physiological and perceptual adaptations.

De novo transcriptome assembly database for 100 tissues from each of seven species of domestic herbivore.

Domesticated herbivores are an important agricultural resource that play a critical role in global food security, particularly as they can adapt to varied environments, including marginal lands. An understanding of the molecular basis of their biology would contribute to better management and sustainable production. Thus, we conducted transcriptome sequencing of 100 to 105 tissues from two females of each of seven species of herbivore (cattle, sheep, goats, sika deer, horses, donkeys, and rabbits) including two breeds of sheep. The quality of raw and trimmed reads was assessed in terms of base quality, GC content, duplication sequence rate, overrepresented k-mers, and quality score distribution with FastQC. The high-quality filtered RNA-seq raw reads were deposited in a public database which provides approximately 54 billion high-quality paired-end sequencing reads in total, with an average mapping rate of ~93.92%. Transcriptome databases represent valuable resources that can be used to study patterns of gene expression, and pathways that are related to key biological processes, including important economic traits in herbivores.

Optimal sampling interval for characterisation of the circadian rhythm of body temperature in homeothermic animals using periodogram and cosinor analysis.

Core body temperature (T c) is a critical aspect of homeostasis in birds and mammals and is increasingly used as a biomarker of the fitness of an animal to its environment. Periodogram and cosinor analysis can be used to estimate the characteristics of the circadian rhythm of T c from data obtained on loggers that have limited memory capacity and battery life. The sampling interval can be manipulated to maximise the recording period, but the impact of sampling interval on the output of periodogram or cosinor analysis is unknown. Some basic guidelines are available from signal analysis theory, but those guidelines have never been tested on T c data. We obtained data at 1-, 5- or 10-min intervals from nine avian or mammalian species, and re-sampled those data to simulate logging at up to 240-min intervals. The period of the rhythm was first analysed using the Lomb-Scargle periodogram, and the mesor, amplitude, acrophase and adjusted coefficient of determination (R 2) from the original and the re-sampled data were obtained using cosinor analysis. Sampling intervals longer than 60 min did not affect the average mesor, amplitude, acrophase or adjusted R 2, but did impact the estimation of the period of the rhythm. In most species, the period was not detectable when intervals longer than 120 min were used. In all individual profiles, a 30-min sampling interval modified the values of the mesor and amplitude by less than 0.1°C, and the adjusted R 2 by less than 0.1. At a 30-min interval, the acrophase was accurate to within 15 min for all species except mice. The adjusted R 2 increased as sampling frequency decreased. In most cases, a 30-min sampling interval provides a reliable estimate of the circadian T c rhythm using periodogram and cosinor analysis. Our findings will help biologists to select sampling intervals to fit their research goals.

Behavioural and physiological responses to stressors in sheep with temperament classified by genotype or phenotype.

The single nucleotide polymorphism (SNP) rs107856856, located in the tryptophan hydroxylase-2 gene, is associated with the behavioural phenotype for sheep temperament measured at weaning. Here, we tested the association between that SNP and physiological and behavioural responses to stressors in adult sheep. Two groups of adult sheep, one with genotype A/A (calm genotype) and the other with G/G (nervous genotype) in rs107856856, were selected from 160 sheep and were exposed, twice, to an open-field arena and an isolation box test (IBT). During each repeat, the behaviour and physiological responses (cortisol, prolactin, dehydroepiandrosterone [DHEA], brain derived neurotrophic factor [BDNF], characteristics of the response of body temperature, and oxidative stress) were measured. The behavioural and physiological responses of the sheep were compared between genotypes and also between groups classified on their phenotype as assessed by their initial isolation box score ("low responders" and "high responders"). The SNP rs107856856 had some effects on the behavioural phenotype (IBT score) but no effects on the physiological response to stress (cortisol, prolactin, DHEA, BDNF, oxidative stress or changes in body temperature) in the adult sheep, probably because the sheep were exposed, and therefore had adapted, to human contact during their life.

Social media as a tool to understand the distribution and ecology of elusive mammals.

Comparatively little is known about the distribution and ecology of Aardvark (Orycteropus afer) and Temminck's Ground Pangolin (Smutsia temminckii). Both are elusive species that are normally nocturnal, solitary, and fossorial. Formally collected records have been used to map the distribution of these species, and social media records provide a tool to gather information on their distribution and ecology. We obtained 680 photographs and videos of aardvarks and 790 of ground pangolins in southern Africa from publicly available posts on Facebook and Instagram (2010-2019). The images provide new insights into the distribution, activity, drinking, and predation-and confirm that aardvarks are more diurnally active when they are in poor body condition. Social media can provide useful supplementary information for understanding of elusive mammals. These "soft" data can be applied to other species.

Functional interactions between coat structure and colour in the determination of solar heat load on arid living kangaroos in summer: balancing crypsis and thermoregulation.

Interactions of solar radiation with mammal fur are complex. Reflection of radiation in the visible spectrum provides colour that has various roles, including sexual display and crypsis, i.e., camouflage. Radiation that is absorbed by a fur coat is converted to heat, a proportion of which impacts on the skin. Not all absorption occurs at the coat surface, and some radiation penetrates the coat before being absorbed, particularly in lighter coats. In studies on this phenomenon in kangaroos, we found that two arid zone species with the thinnest coats had similar effective heat load, despite markedly different solar reflectances. These kangaroos were Red Kangaroos (Osphranter rufus) and Western Grey Kangaroos (Macropus fuliginosus).Here we examine the connections between heat flow patterns associated with solar radiation, and the physical structure of these coats. Also noted are the impacts of changing wind speed. The modulation of solar radiation and resultant heat flows in these coats were measured at wind speeds from 1 to 10 m s-1 by mounting them on a heat flux transducer/temperature-controlled plate apparatus in a wind tunnel. A lamp with a spectrum like solar radiation was used as a proxy for the sun. The integrated reflectance across the solar spectrum was higher in the red kangaroos (40 ± 2%) than in the grey kangaroos (28 ± 1%). Fur depth and insulation were not different between the two species, but differences occurred in fibre structure, notably in fibre length, fibre density and fibre shape. Patterns of heat flux within the species' coats occurred despite no overall difference in effective solar heat load. We consider that an overarching need for crypsis, particularly for the more open desert-adapted red kangaroo, has led to the complex adaptations that retard the penetrance of solar radiation into its more reflective fur.

Finding biomarkers of experience in animals.

At a time when there is a growing public interest in animal welfare, it is critical to have objective means to assess the way that an animal experiences a situation. Objectivity is critical to ensure appropriate animal welfare outcomes. Existing behavioural, physiological, and neurobiological indicators that are used to assess animal welfare can verify the absence of extremely negative outcomes. But welfare is more than an absence of negative outcomes and an appropriate indicator should reflect the full spectrum of experience of an animal, from negative to positive. In this review, we draw from the knowledge of human biomedical science to propose a list of candidate biological markers (biomarkers) that should reflect the experiential state of non-human animals. The proposed biomarkers can be classified on their main function as endocrine, oxidative stress, non-coding molecular, and thermobiological markers. We also discuss practical challenges that must be addressed before any of these biomarkers can become useful to assess the experience of an animal in real-life.

Neurotrophic factor MANF regulates autophagy and lysosome function to promote proteostasis in C. elegans.

The conserved mesencephalic astrocyte-derived neurotrophic factor (MANF) protects dopaminergic neurons but also functions in several other tissues. Previously, we showed that Caenorhabditis elegans manf-1 null mutants have increased ER stress, dopaminergic neurodegeneration, protein aggregation, slower growth, and a reduced lifespan. The multiple requirements of MANF in different systems suggest its essential role in regulating cellular processes. However, how intracellular and extracellular MANF regulates broader cellular function remains unknown. Here, we report a novel mechanism of action for manf-1 that involves the autophagy transcription factor HLH-30/TFEB-mediated signaling to regulate lysosomal function and aging. We generated multiple transgenic strains overexpressing MANF-1 and found that animals had extended lifespan, reduced protein aggregation, and improved neuronal health. Using a fluorescently tagged MANF-1, we observed different tissue localization of MANF-1 depending on the ER retention signal. Further subcellular analysis showed that MANF-1 localizes within cells to the lysosomes. These findings were consistent with our transcriptomic studies and, together with analysis of autophagy regulators, demonstrate that MANF-1 regulates protein homeostasis through increased autophagy and lysosomal activity. Collectively, our findings establish MANF as a critical regulator of the stress response, proteostasis, and aging.

Correction: Could the ketogenic diet induce a shift in thyroid function and support a metabolic advantage in healthy participants? A pilot randomized-controlled-crossover trial.

[This corrects the article DOI: 10.1371/journal.pone.0269440.].

Effect of Neck-Deep Immersion in Cool or Thermoneutral Water on Blood Glucose Levels in Individuals With Type 1 Diabetes.

Context: It is unclear whether immersion in cool water, typical of many beaches, increases the concentration of blood glucose in individuals with type 1 diabetes mellitus (T1DM). Objective: To test the hypothesis in individuals with T1DM that immersion neck-deep in cool water (COOL) causes an increase in blood glucose concentration, but not exposure to thermoneutral water (THERMO) or thermoneutral air. Methods: Eight overnight-fasted participants with T1DM were exposed for 60 minutes on separate days to 3 experimental conditions: cool water (COOL, 23 °C); thermoneutral water (THERMO, 33.5 °C); or thermoneutral air (24 °C). They then recovered for 60 minutes on land at 24 °C. At time intervals, we measured: blood glucose and plasma insulin concentration, rate of carbohydrate and fat oxidation, skin and core temperature, subcutaneous blood flow, and shivering via electromyography. Results: There was no change in blood glucose concentration during the 3 experimental conditions (P > .05). During recovery after COOL, blood glucose increased (P < .05) but did not change in the other 2 conditions. The rate of carbohydrate oxidation during and early after COOL was higher than in the other 2 conditions (P < .05), and COOL led to a decrease in subcutaneous blood flow and the concentration of plasma insulin (P < .05). Conclusion: Cool or thermoneutral neck-deep immersion in water does not cause a change in the concentration of blood glucose in people with T1DM, but on-land recovery from COOL causes an increase in blood glucose that may be due, at least in part, to the accompanying decrease in plasma insulin.

Effect of starvation on electrotaxis response.

Caenorhabditis elegans is an ideal model for investigating the effects of extrinsic and intrinsic conditions on the behavioral changes of animals. Our group previously showed how different conditions influence the behavior of worms following an electric stimulus in a microfluidic channel, known as electrotaxis. In this study we describe the effect of starvation on the electrotaxis movement of animals. We show that acute starvation did not affect the electrotaxis response or dopaminergic neurons but extended the lifespan of animals.

Cold and Hungry: Heterothermy Is Associated with Low Leptin Levels in a Bulk Grazer during a Drought.

AbstractReduced energy intake can compromise the ability of a mammal to maintain body temperature within a narrow 24-h range, leading to heterothermy. To investigate the main drivers of heterothermy in a bulk grazer, we compared abdominal temperature, body mass, body condition index, and serum leptin levels in 11 subadult Cape buffalo (Syncerus caffer caffer) during a drought year and a nondrought year. Low food availability during the drought year (as indexed by grass biomass, satellite imagery of vegetation greenness, and fecal chlorophyll) resulted in lower body condition index, lower body mass relative to that expected for an equivalent-aged buffalo, and lower leptin levels. The range of 24-h body temperature rhythm was 2°C during the nondrought year and more than double that during the drought year, and this was caused primarily by a lower minimum 24-h body temperature rhythm during the cool dry winter months. After rain fell and vegetation greenness increased, the minimum 24-h body temperature rhythm increased, and the range of 24-h body temperature rhythm was smaller than 2°C. In order of importance, poor body condition, low minimum 24-h air temperature, and low serum leptin levels were the best predictors of the increase in the range of 24-h body temperature rhythm. While the thermoregulatory role of leptin is not fully understood, the association between range of 24-h body temperature rhythm and serum leptin levels provides clues about the underlying mechanism behind the increased heterothermy in large mammals facing food restriction.

Finding motifs using DNA images derived from sparse representations.

MOTIVATION: Motifs play a crucial role in computational biology, as they provide valuable information about the binding specificity of proteins. However, conventional motif discovery methods typically rely on simple combinatoric or probabilistic approaches, which can be biased by heuristics such as substring-masking for multiple motif discovery. In recent years, deep neural networks have become increasingly popular for motif discovery, as they are capable of capturing complex patterns in data. Nonetheless, inferring motifs from neural networks remains a challenging problem, both from a modeling and computational standpoint, despite the success of these networks in supervised learning tasks. RESULTS: We present a principled representation learning approach based on a hierarchical sparse representation for motif discovery. Our method effectively discovers gapped, long, or overlapping motifs that we show to commonly exist in next-generation sequencing datasets, in addition to the short and enriched primary binding sites. Our model is fully interpretable, fast, and capable of capturing motifs in a large number of DNA strings. A key concept emerged from our approach-enumerating at the image level-effectively overcomes the k-mers paradigm, enabling modest computational resources for capturing the long and varied but conserved patterns, in addition to capturing the primary binding sites. AVAILABILITY AND IMPLEMENTATION: Our method is available as a Julia package under the MIT license at https://github.com/kchu25/MOTIFs.jl, and the results on experimental data can be found at https://zenodo.org/record/7783033.

Seasonal activities of the phyllosphere microbiome of perennial crops.

Understanding the interactions between plants and microorganisms can inform microbiome management to enhance crop productivity and resilience to stress. Here, we apply a genome-centric approach to identify ecologically important leaf microbiome members on replicated plots of field-grown switchgrass and miscanthus, and to quantify their activities over two growing seasons for switchgrass. We use metagenome and metatranscriptome sequencing and curate 40 medium- and high-quality metagenome-assembled-genomes (MAGs). We find that classes represented by these MAGs (Actinomycetia, Alpha- and Gamma- Proteobacteria, and Bacteroidota) are active in the late season, and upregulate transcripts for short-chain dehydrogenase, molybdopterin oxidoreductase, and polyketide cyclase. Stress-associated pathways are expressed for most MAGs, suggesting engagement with the host environment. We also detect seasonally activated biosynthetic pathways for terpenes and various non-ribosomal peptide pathways that are poorly annotated. Our findings support that leaf-associated bacterial populations are seasonally dynamic and responsive to host cues.