Body Temperatures Research Articles

Therapeutic potential of Garcinia kola against experimental toxoplasmosis in rats.

Cerebral toxoplasmosis, the most common opportunistic infection in immunocompromised individuals, is increasingly reported in immunocompetent individuals due to mutant strains of Toxoplasma gondii, which, furthermore, are reported to be resistant to available treatments. We assessed the therapeutic potential of Garcinia kola, a medicinal plant reported to have antiplasmodial and neuroprotective properties, against experimental toxoplasmosis in rats. Severe toxoplasmosis was induced in male Wistar rats (156.7 ± 4.1 g) by injecting them with 10 million tachyzoites in suspension in 500 µl of saline (intraperitoneal), and exclusive feeding with a low-protein diet [7% protein (weight by weight)]. Then, animals were treated with hexane, dichloromethane, and ethyl acetate fractions of Garcinia kola. Footprints were analysed and open-field and elevated plus maze ethological tests were performed when symptoms of severe disease were observed in the infected controls. After sacrifice, blood samples were processed for Giemsa staining, organs were processed for haematoxylin and eosin staining, and brains were processed for Nissl staining and cell counting. Compared with non-infected animals, the infected control animals had significantly lower body weights (30.27%↓, P = 0.001), higher body temperatures (P = 0.033) during the sacrifice, together with signs of cognitive impairment and neurologic deficits such as lower open-field arena centre entries (P < 0.001), elevated plus maze open-arm time (P = 0.029) and decreased stride lengths and step widths (P < 0.001), as well as neuronal loss in various brain areas. The ethyl acetate fraction of Garcinia kola prevented or mitigated most of these signs. Our data suggest that the ethyl acetate fraction of Garcinia kola has therapeutic potential against cerebral toxoplasmosis.

The effects of humidity on thermoregulatory physiology of a small songbird.

Scholander-Irving curves describe the relationship between ambient temperature and metabolic rate and are fundamental to understanding the energetic demands of homeothermy. However, Scholander-Irving curves are typically measured in dry air, which is not representative of the humidity many organisms experience in nature. Consequently, it is unclear (1) whether Scholander-Irving curves (especially below thermoneutrality) are altered by humidity, given the effects of humidity on thermal properties of air, and (2) whether physiological responses associated with Scholander-Irving curves in the lab reflect organismal performance in humid field conditions. We used laboratory experiments and biophysical models to test the effects of humidity on the thermoregulatory physiology of tree swallows (Tachycineta bicolor). We also tested whether physiological responses measured under lab conditions were correlated with field body temperatures and nestling provisioning rates. We found that humidity reduced rates of evaporative water loss but did not have large effects on body temperature or metabolic rate, suggesting that swallows can decouple evaporative cooling, body temperature and metabolic rate. Although the effect of humidity on metabolic rate in the lab was small, our biophysical models indicated that energetic costs of thermoregulation were ∼8% greater in simulations that used metabolic rates from birds in humid compared with dry conditions. Finally, we found mixed evidence that physiological responses measured in the lab under humid or dry conditions were associated with body temperature and nest provisioning rates in the field. Our results help clarify the effect of humidity on endotherm thermoregulation, which may help forecast organismal responses to environmental change.

Cold kiss still hot: limited temperature effects on envenomation performance in predatory strikes of a Japanese pit viper (Gloydius blomhoffii).

Understanding how environmental factors affect the performance of predators can provide profound insights into predator-prey interactions from evolutionary and ecological perspectives and the global distributional patterns of each taxon. Almost all venomous predators are ectotherms, with muscle contraction properties depending on temperature. For predators having venom transportation systems driven by muscle contraction, temperature may have quite large effects on envenomation performance for prey subjugation. Here, we used videography and enzyme-linked immunosorbent assay to examine thermal effects on envenomation kinematics and venom expenditure in predatory strikes of a venomous snake, the Mamushi Gloydius blomhoffii, to its main rodent prey at various body temperatures under both field and laboratory experimental conditions. Unexpectedly, we found that the thermal effects on envenomation performance are limited over nearly the entire ecologically relevant range of temperature (from 13.2°C to 26.2°C). Although temperature statistically significantly affected the mass of venom injected under field conditions, temperature explained only a minor proportion of the variation in venom expenditure. These findings suggest that the Mamushi is able to maintain prey subjugation performance across a wide range of temperatures, which is highly advantageous for ectothermic predators. Further studies should examine the underlying mechanisms of the limited thermal effects and their ubiquity across venomous predators.

Thermal tolerance plasticity and dynamics of thermal tolerance in Eublepharis macularius: Implications for future climate-driven heat stress

The intensity and duration of heat waves, as well as average global temperatures, are expected to increase due to climate change. Heat waves can cause physiological stress and reduce fitness in animals. Species can reduce overheating risk through phenotypic plasticity, which allows them to raise their thermal tolerance limits over time. This mechanism could be important for ectotherms whose body temperatures are directly influenced by available environmental temperatures. Geckos are a large, diverse group of ectotherms that vary in their thermal habitats and times of daily activity, which could affect how they physiologically adjust to heat waves. Data on thermal physiology are scarce for reptiles, with only one study in geckos. Understanding thermal tolerance and plasticity, and their relationship, is essential for understanding how some species are able to adjust or adapt to changing temperatures. In this study, we estimated thermal tolerance and plasticity, and their interaction, in the crepuscular gecko, Eublepharis macularius, a species that is emerging as a model for reptile biology. After estimating basal thermal tolerance for 28 geckos, thermal tolerance was measured for each individual a second time at several timepoints (3, 6, or 24 h) to determine thermal tolerance plasticity. We found that thermal tolerance plasticity (1) does not depend on the basal thermal tolerance of the organism, (2) was highest after 6 h from initial heat shock, and (3) was negatively influenced by individual body mass. Our findings contribute to the increasing body of work focused on understanding the influence of biological and environmental factors on thermal tolerance plasticity in organisms and provide phenotypic data to further investigate the molecular basis of thermal tolerance plasticity in organisms.

Martensitic transformation temperature modification of Fe-SMA for efficient medical implants

Nickel-Titanium alloys or Nitinol shape memory alloys have applications in various fields like biomedical, agriculture, pharmaceutical, civil, and mechanical engineering. Ferrous-based shape memory alloys (Fe-SMAs) do not possess excellent properties like that of Nitinol. In recent times, Fe-SMAs have been under consideration in the research field to enhance their shape memory properties because of their cost-effectiveness, corrosion resistance, biocompatibility, and high mechanical strength. Fe-SMAs are limited in their applications in the human body due to high austenite start temperature () even though they are biocompatible and being considered for temporary biodegradable implant applications. Several factors affect the phase transformation temperature of Fe-SMA, like alloy composition and heat treatment conditions. Some of the techniques that are useful to reduce the are quenching, solid solution treatment, ternary element addition, alloying, and thermal-mechanical treatment. In this study, the quenching with brine solution is used to reduce of Fe-15Mn-10 Cr-8Ni-4Si (wt. %). The phase transformation is observed using Differential Scanning Calorimetry (DSC). The best result from experimentation of all the samples collected as reduced from 93oC to 39.02oC which is very close to the temperature of the human body. The results of this study exhibit significant potential for advancement in the application of Fe-SMAs in the biomedical field for permanent implants in cardiovascular and orthopaedic applications.

The heat is on: Thermoregulatory and evaporative cooling patterns of desert-dwelling bats

For small endotherms inhabiting desert ecosystems, defending body temperatures (Tb) is challenging as they contend with extremely high ambient temperatures (Ta) and limited standing water. In the arid zone, bats may thermoconform whereby Tb varies with Ta, or may evaporatively cool themselves to maintain Tb < Ta. We used an integrative approach that combined both temperature telemetry and flow through respirometry to investigate the ecological and physiological strategies of lesser long-eared bats (Nyctophilus geoffroyi) in Australia's arid zone. We predicted individuals would exhibit desert-adapted thermoregulatory patterns (i.e., thermoconform to prioritise water conservation), and that females would be more conservative with their water reserves for evaporative cooling compared to males. Temperature telemetry data indicated that free-ranging N. geoffroyi were heterothermic (Tskin = 18.9–44.9 °C) during summer and thermoconformed over a wide range of temperatures, likely to conserve water and energy during the day. Experimentally, at high Tas, females maintained significantly lower Tb and resting metabolic rates, despite lower evaporative water loss (EWL) rates compared to males. Females only increased EWL at experimental Ta = 42.5 °C, significantly higher than males (40.7 °C), and higher than any bat species yet recorded. During the hottest day of this study, our estimates suggest the water required for evaporative cooling ranged from 18.3% (females) and 25.5% (males) of body mass. However, if we extrapolate these results to a recent heatwave these values increase to 36.5% and 47.3%, which are likely beyond lethal limits. It appears this population is under selective pressures to conserve water reserves and that these pressures are more pronounced in females than males. Bats in arid ecosystems are threatened by both current and future heatwaves and we recommend future conservation efforts focus on protecting current roost trees and creating artificial standing water sites near vulnerable populations.

Intraspecific variation in morphology and thermal ecology of the cleft lizard Sceloporus mucronatus (Squamata Phrynosomatidae): effect of habitat and sex

Populations of the same species that inhabit contrasting environments may be subject to different selection pressures, promoted by the local environment. Therefore, the individuals of the different populations respond to these pressures with adaptations to local environments; however, not all species or populations respond in the same way. We compared some morphological and ecological traits of the lizard Sceloporus mucronatus that inhabits contrasting environments in central Mexico. The results show male-biased sexual size dimorphism in Tecocomulco, but no differences in size between sexes in Parque Nacional El Chico (PNCH). Significant differences were observed in morphometric traits and in body mass between sexes and populations, but not in the interaction between these two factors. In general, females were heavier than males, while males had larger head structures, jaws, and hind limbs than females. In addition, differences were recorded in the volume of the abdomen, which was female-biased in the PNCH, and male-biased in Tecocomulco. Between populations, it was recorded that the organisms from the PNCH were heavier and had larger heads than those from Tecocomulco. Thermal traits showed differences among populations, but not between sexes nor in the interaction among these factors. Individuals from the locality with lower temperature and higher precipitation (PNCH) reached higher body temperatures and used warmer microhabitats than those individuals from the locality with higher temperature and lower precipitation (Tecocomulco). Females from both populations showed a greater degree of active thermoregulation compared to males. In addition, in both sexes and populations, average values of behavioral thermoregulation were different from zero. Significant differences were recorded in microhabitat use between populations. In agreement with previous studies of morphology and thermal ecology carried out in this species from this and other localities, and in different years, we suggest that its populations present a wide phenotypic plasticity.

Assessing the possibility of using a variable-length launch vehicle with a polymer body for orbiting payload

The object of this study was the motion of an ultralight class variable-length launch vehicle made of a polymer body along the active phase of the trajectory. The work considers the solution to the problem of designing low-cost means of delivery to orbit, namely to the assessment of the possibility of removing the payload by a carrier rocket with a polymer body of variable length beyond the dense atmosphere of the Earth. For this purpose, ballistic projection of the trajectory of the launch vehicle was carried out taking into account overloading; its aerodynamic characteristics and peculiarities of aerothermodynamic processes occurring during flight in the atmospheric phase of the trajectory were determined. The closeness (up to 10 %) of the obtained results with known experimental data is shown. The influence of the aerodynamic force on the parameters of the launch vehicle motion was studied. A flight simulation was conducted, the results of which showed the fundamental possibility of launching a CubeSat 24U class payload using a launch vehicle with a polymer body of variable length to a suborbital trajectory with an altitude of about 300 km. At the same time, the effective longitudinal overload on the body of the launch vehicle does not exceed 4 units, and the temperature on the surface of the body does not exceed 300 K. A feature of the research is the use of a multidisciplinary approach, which implies taking into account the interrelationship of aerodynamic, thermodynamic, and ballistic processes. The established motion parameters, aerodynamic characteristics, and the surface heating temperature of the launch vehicle body are key values for further research on the design and analysis of a launch vehicle with a polymer body of variable length. These data could be used to calculate the mechanical and thermal loads acting on the structure of the launch vehicle during flight

Microcalorimetric study of the bactericidal action of titanium tetrachloride on the Pseudomonas aeruginosa growth. Potential implications in orthopaedic surgery

With the rising use of metallic implants worldwide, bacterial infection has become a major concern due to its significant impact on patient health and national healthcare budgets. This study aimed to evaluate the sensitivity of Pseudomonas aeruginosa, a common bacterium responsible for implant surgery infections, to different concentrations of titanium tetrachloride (TiCl4) solutions. Microcalorimetry was used to analyze the heat output produced by bacteria metabolism when exposed to TiCl4 at concentrations ranging from 0 to 10 mM, as well as a saturated solution. The inner chamber of the calorimeter was set to the physiological temperature of the human body (309.65 K), and the heat output produced by bacteria metabolism was collected at intervals of 22.2 s for 48 h using a data acquisition and processing system. The data was then represented as thermograms. The results showed that higher concentrations of TiCl4 had a bactericidal effect on the growth of Pseudomonas aeruginosa. This study supports the potential use of higher concentrations of this compound in surgical implants to reduce the risk of infection development due to its bactericidal properties.

Bring on the heat: thermal ecology of Tropidurus semitaeniatus in the Northeast of Brazil

Body temperature is a key physiological trait for individual fitness. Its effects on behavior and metabolism determine organismal activity. Optimal body temperature can vary among individuals, and consequent activity asynchrony can thus enable the co-occurrence of otherwise competing social strategies. Here, we combine ex-situ experiments with environmental data to test whether variability in thermal traits can explain the maintenance of the alternative reproductive strategies of Tropidurus semitaeniatus (Spix, 1825) male morphs. We predict that morphs and sexes differ in thermal traits. Thus, we tested for differences in their behaviorally determined thermal traits: preferred ( Tp), body ( Tb), and habitat temperatures; basking cover preference (Coverpref); and physiological limits (critical thermal minimum CTmin; and maximum, CTmax). We also calculated T. semitaeniatus’ thermal tolerance traits and compiled a list of Tp for Tropidurids. We found that T. semitaeniatus maintains its Tb below Tp. In addition, and contrary to theoretical predictions for tropical lizards, we found that T. semitaeniatus has a high warming tolerance (8.3 °C) and thermal safety margin (2.4 °C). We found no thermal differences between morphs indicating that thermal ecology does not play a role in the co-existence of color morphs.

Hotspot shelters stimulate frog resistance to chytridiomycosis.

Many threats to biodiversity cannot be eliminated; for example, invasive pathogens may be ubiquitous. Chytridiomycosis is a fungal disease that has spread worldwide, driving at least 90 amphibian species to extinction, and severely affecting hundreds of others1-4. Once the disease spreads to a new environment, it is likely to become a permanent part of that ecosystem. To enable coexistence with chytridiomycosis in the field, we devised an intervention that exploits host defences and pathogen vulnerabilities. Here we show that sunlight-heated artificial refugia attract endangered frogs and enable body temperatures high enough to clear infections, and that having recovered in this way, frogs are subsequently resistant to chytridiomycosis even under cool conditions that are optimal for fungal growth. Our results provide a simple, inexpensive and widely applicable strategy to buffer frogs against chytridiomycosis in nature. The refugia are immediately useful for the endangered species we tested and will have broader utility for amphibian species with similar ecologies. Furthermore, our concept could be applied to other wildlife diseases in which differences in host and pathogen physiologies can be exploited. The refugia are made from cheap and readily available materials and therefore could be rapidly adopted by wildlife managers and the public. In summary, habitat protection alone cannot protect species that are affected by invasive diseases, but simple manipulations to microhabitat structure could spell the difference between the extinction and the persistence of endangered amphibians.

Establishment and risk factor assessment of the abnormal body temperature probability prediction model (ABTP) for dairy cattle

The study aims to develop an abnormal body temperature probability (ABTP) model for dairy cattle, utilizing environmental and physiological data. This model is designed to enhance the management of heat stress impacts, providing an early warning system for farm managers to improve dairy cattle welfare and farm productivity in response to climate change. The study employs the Least Absolute Shrinkage and Selection Operator (LASSO) algorithm to analyze environmental and physiological data from 320 dairy cattle, identifying key factors influencing body temperature anomalies. This method supports the development of various models, including the Lyman Kutcher-Burman (LKB), Logistic, Schultheiss, and Poisson models, which are evaluated for their ability to predict abnormal body temperatures in dairy cattle effectively. The study successfully validated multiple models to predict abnormal body temperatures in dairy cattle, with a focus on the temperature-humidity index (THI) as a critical determinant. These models, including LKB, Logistic, Schultheiss, and Poisson, demonstrated high accuracy, as measured by the AUC and other performance metrics such as the Brier score and Hosmer–Lemeshow (HL) test. The results highlight the robustness of the models in capturing the nuances of heat stress impacts on dairy cattle. The research develops innovative models for managing heat stress in dairy cattle, effectively enhancing detection and intervention strategies. By integrating advanced technologies and novel predictive models, the study offers effective measures for early detection and management of abnormal body temperatures, improving cattle welfare and farm productivity in changing climatic conditions. This approach highlights the importance of using multiple models to accurately predict and address heat stress in livestock, making significant contributions to enhancing farm management practices.

Autecology of the gecko Phyllopezus periosus (Squamata: Phyllodactylidae) inhabiting rock cliffs of a waterfall canyon from the semi-arid region of northeastern Brazil

Phyllopezus periosus is the largest phyllodactilid in Brazil, with a relictual distribution in the Caatinga Domain. Herein, we investigated the autecology of P. periosus, describing activity patterns, microhabitat use (spatial niche dimension), foraging mode, body temperature, reproduction, diet (trophic niche dimension), and temperature. Also, we tested the influence of seasonality and ontogeny on these biological aspects. Geckos (n = 116, 54 females, 33 males, and 29 juveniles) were sampled from October 2013 to September 2014. Phyllopezus periosus has an unimodal activity pattern, with peak activity in the early hours of the night. Males are more robust than females, and forelimbs in females are longer than in males. The body temperatures of this thermoconformer gecko are higher in the dry season. The reproductive season begins in the early dry season, with a fixed clutch of two eggs. Although we did not find evidence of more than one clutch per year, the studied population of P. periosus reproduces for an extended period throughout the dry season, as highlighted by the presence of juveniles all year. Phyllopezus periosus is saxicolous and presents a generalist diet composed mainly of arthropods, also including vertebrates such as frogs and lizards.

The intersection-of-asymptotes method applied to the study of skin temperature changes over time during running exercise

The intersection of asymptotes method is used to describe the changes in skin temperature of the human body during running exercise. Skin temperature variations are induced by thermoregulatory mechanisms, which are influenced by both physiological and environmental factors. The aim of this study is to succinctly and comprehensively connect these factors to create an easily interpretable tool for understanding this process. Based on simplified energy balance equations under dynamic conditions for both the early and late stages of exercise, two asymptotic solutions for skin temperature are derived. The point of intersection between these solutions determines the moment at which the transition from skin vasoconstriction to vasodilation occurs. The shapes and the intersection of the two asymptotes enable the inference and interpretation of actual skin temperature variations throughout the course of exercise.

Rapid in vitro activity of telavancin against Bacillus anthracis and in vivo protection against inhalation anthrax infection in the rabbit model.

Inhalation anthrax is the most severe form of Bacillus anthracis infection, often progressing to fatal conditions if left untreated. While recommended antibiotics can effectively treat anthrax when promptly administered, strains engineered for antibiotic resistance could render these drugs ineffective. Telavancin, a semisynthetic lipoglycopeptide antibiotic, was evaluated in this study as a novel therapeutic against anthrax disease. Specifically, the aims were to (i) assess in vitro potency of telavancin against 17 B. anthracis isolates by minimum inhibitory concentration (MIC) testing and (ii) evaluate protective efficacy in rabbits infected with a lethal dose of aerosolized anthrax spores and treated with human-equivalent intravenous telavancin doses (30 mg/kg every 12 hours) for 5 days post-antigen detection versus a humanized dose of levofloxacin and vehicle control. Blood samples were collected at various times post-infection to assess the level of bacteremia and antibody production, and tissues were collected to determine bacterial load. The animals' body temperatures were also recorded. Telavancin demonstrated potent bactericidal activity against all strains tested (MICs 0.06-0.125 μg/mL). Further, telavancin conveyed 100% survival in this model and cleared B. anthracis from the bloodstream and organ tissues more effectively than a humanized dose of levofloxacin. Collectively, the low MICs against all strains tested and rapid bactericidal in vivo activity demonstrate that telavancin has the potential to be an effective alternative for the treatment or prophylaxis of anthrax infection.

COMPREHENSIVE EVALUATION OF THERMAL PERFORMANCE AND TIME-LAG IN RESIDENTIAL APARTMENTS IN AMMAN

This exploration investigates the potential of enhancing energy efficiency in residential structures in Amman, Jordan, by introducing an innovative material termed "Phase Transition Substance with Fungal Integration (PTSF)." Through computational simulations using Autodesk-Revit, the analysis evaluates the thermal efficiency of a standard residential building, contrasting traditional construction materials with PTSF. The study centers on three crucial elements: outer walls (W.01), roof (R.01), and ground level slab (S.01), all initially not meeting prescribed thermal conductivity regulations. Integration of PTSF notably improves the thermal efficacy of the building's shell, aligning with Jordanian standards for thermal insulation. Furthermore, a systematic examination explores the time delay of materials within the residential envelope, revealing an average lag of approximately 8 hours. This lag implies that, with the incorporation of the PTSF layer, the envelope requires 8 hours to transmit external temperatures (e.g., 30°C) to attain the interior's peak temperature, underscoring the material's potential in curbing energy consumption.

Altitudinal variation in thermal vulnerability of Qinghai-Tibetan Plateau lizards under climate warming

Abstract The survival of ectotherms worldwide is threatened by climate change. Whether increasing temperatures increase the vulnerability of ectotherms inhabiting temperate plateau areas remains unclear. To understand altitudinal variation in the vulnerability of plateau ectotherms to climate warming, Qinghai toad-headed lizards (Phrynocephalus vlangalii) were subjected to semi-natural enclosure experiments with simulated warming at high (2,600 m) and superhigh (3,600 m) elevations of the Dangjin Mountain, China. Our results revealed that the thermoregulatory effectiveness and warming tolerance (WT) of the toad-headed lizards were significantly affected by climate warming at both elevations, but their thermal sensitivity remained unchanged. After warming, the thermoregulatory effectiveness of lizards at superhigh elevations decreased because of the improved environmental thermal quality, whereas that of lizards at high-elevation conditions increased. Although the body temperature selected by high-elevation lizards was also significantly increased, the proportion of their active body temperature falling within the set-point temperature range decreased. This indicates that it is difficult for high-elevation lizards to adjust their body temperatures within a comfortable range under climate warming. Variations in the WT and thermal safety margin (TSM) under climate warming revealed that lizards at the superhigh elevation benefited from improved environmental thermal quality, whereas those at the high elevation originally on the edge of the TSM faced more severe threats and became more vulnerable. Our study highlights the importance of thermal biological traits in evaluating the vulnerability of ectotherms in temperate plateau regions.

Temperature effect on coagulation function in mild hypothermic patients undergoing thoracic surgeries: thromboelastography (TEG) versus standard tests

PurposeOur previous research has revealed that mild hypothermia leads to excessive bleeding in thoracic surgeries, while the underlying mechanism stayed unrevealed by the standard coagulation tests. The research question in this study was as follows: “How does mild hypothermia impair the hemostatic function in patients receiving thoracic surgeries?”. The purpose was to detect the disturbed coagulation processes by comparing the TEG parameters in patients receiving active vs. passive warming during thoracic surgeries.MethodsStandard coagulation tests and thromboelastography (TEG) were adopted to compare the hemostatic functions in patients receiving active vs. passive warming during thoracic surgeries. Furthermore, blood samples from passive warming group were retested for TEG at actual core body temperatures.ResultsSixty-four eligible patients were included in this study. TEG revealed that mild hypothermia significantly disturbed coagulation by decreasing MA (59.4 ± 4.5 mm vs. 64.2 ± 5.7 mm, p = 0.04) and α angle (70.4 ± 5.2° vs. 74.9 ± 4.4°, p = 0.05) and prolonging ACT (122.2 ± 19.3 s vs. 117.3 ± 15.2 s, p = 0.01) and K time (1.9 ± 1.0 s vs. 1.3 ± 0.4 min, p = 0.02). TEGs conducted under core body temperatures revealed more impaired coagulation than those incubated at 37 °C. Furthermore, postoperative shivering and waking time were significantly increased in mild hypothermic patients.ConclusionMild hypothermia significantly impaired coagulation function in patients receiving thoracic surgeries, which could be detected by TEGs other than the standard coagulation tests. Temperature-adjusted TEGs may provide a preferable method of hemostatic monitoring and transfusion guidance in thoracic surgeries, which warrants further clinical investigations.

GENETIC ABLATION OF THE C-TYPE LECTIN RECEPTOR CLEC2D INCREASES PERITONITIS MORTALITY, INFLAMMATION, AND PHYSIOLOGY WITHOUT DIMINISHING ORGAN INJURY.

Background: Sepsis accounts for substantial morbidity and mortality motivating investigators to continue the search for pathways and molecules driving the pathogenesis of the disease. The current study examined if the novel C-type lectin receptor (CLR), Clec2d, plays a significant role in the pathogenesis of sepsis. Methods: Clec2d knockout (KO) mice were fully backcrossed onto the C57/BL6 background. Acute endotoxemia was induced with an intraperitoneal injection of lipopolysaccharide (LPS). Sepsis was induced in two different models, cecal ligation and puncture (CLP) and Pseudomonas aeruginosa pneumonia. Both models were treated with antibiotics and fluid resuscitation. In the sepsis models, physiologic and hematologic measurements were measured at 24 h by collecting a small sample of peripheral blood. Mortality was followed for 14 days. Results : A total of 197 mice were studied, 58 wild type (WT) and 54 knock-out (KO) in the LPS model; 27 wild type and 21 KO mice in the CLP model; and 22 WT and 15 KO mice in the pneumonia model. Clec2d KO mice had greater mortality in the LPS and CLP studies but not the pneumonia model. There were significant differences in multiple parameters determined 24 h post sepsis between mice who subsequently died and those lived. Consistent with previous reports in the CLP model, higher concentrations of IL-6, increased numbers of peripheral blood lymphocytes and greater renal injury were found in the dying mice. In contrast, in the pneumonia model, IL-6 was higher in the surviving mice; however, the IL-6 levels in the pneumonia model (0.6 ± 0.3 ng/mL mean ± SEM) were less than 2% of the IL-6 levels of mice that died in the CLP model (41 ± 9 ng/mL, mean ± SEM). There were no differences in the lymphocyte count or renal injury between living and dying mice in the pneumonia model. In both sepsis models, dying mice had lower heart rates, respiratory rates, and body temperatures. These values were also lower in the KO mice compared to the WT in CLP, but the breath rate and body temperature were increased in the KO pneumonia mice. Conclusion: The C-type lectin receptor Clec2d plays a complicated role in the pathogenesis of sepsis, which varies with source of infection as demonstrated in the models used to study the disease. These data highlight the heterogeneity of the responses to sepsis and provide further evidence that a single common pathway driving sepsis organ injury and death likely does not exist.

Two-stage evolution of mammalian adipose tissue thermogenesis.

Brown adipose tissue (BAT) is a heater organ that expresses thermogenic uncoupling protein 1 (UCP1) to maintain high body temperatures during cold stress. BAT thermogenesis is considered an overarching mammalian trait, but its evolutionary origin is unknown. We show that adipose tissue of marsupials, which diverged from eutherian mammals ~150 million years ago, expresses a nonthermogenic UCP1 variant governed by a partial transcriptomic BAT signature similar to that found in eutherian beige adipose tissue. We found that the reconstructed UCP1 sequence of the common eutherian ancestor displayed typical thermogenic activity, whereas therian ancestor UCP1 is nonthermogenic. Thus, mammalian adipose tissue thermogenesis may have evolved in two distinct stages, with a prethermogenic stage in the common therian ancestor linking UCP1 expression to adipose tissue and thermal stress. We propose that in a second stage, UCP1 acquired its thermogenic function specifically in eutherians, such that the onset of mammalian BAT thermogenesis occurred only after the divergence from marsupials.