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Extreme Temperature and Incident Diabetes Risk Among Middle-Aged and Older Adults in China: A National Longitudinal Cohort Study.

BACKGROUND AND AIMS: The metabolic consequences of extreme temperature exposure in nondiabetic populations remain poorly understood. This study aimed to examine associations between heatwave and coldwave exposure and incident diabetes mellitus (DM) and impaired glucose tolerance (IGT) in middle-aged and older Chinese adults. METHODS: A total of 1803 China Health and Retirement Longitudinal Study participants aged &#x2265;45 years with normoglycemia at baseline were followed from Wave 1 (2011) to Wave 3 (2015). Eighteen extreme-temperature indicators were derived from city-level fifth-generation European Centre for Medium-Range Weather Forecasts atmospheric reanalysis data. Outcomes were classified according to American Diabetes Association criteria. Generalized linear mixed-effects models (GLMMs) were pooled across five imputed datasets, with Bonferroni correction for multiple comparisons (&#x3b1; = 0.0028) and sensitivity analysis adjusting for individual follow-up duration. RESULTS: All nine heatwave indicators showed odds ratios (ORs) < 1.0 for DM and IGT. HT9 (&#x2265;97.5th percentile, &#x2265;4 consecutive days) was the sole Bonferroni-significant result: OR = 0.845 (95% confidence interval [CI]: 0.802-0.890). Coldwave indicators showed no consistent associations. Age significantly modified the HT9 effect (P-interaction = 0.004): adults aged 65-84 showed a stronger inverse association (OR = 0.616) than those aged < 65 (OR = 0.921). CONCLUSION: Prolonged heatwave exposure was consistently associated with reduced diabetes risk, with pronounced age heterogeneity. Replication in larger prospective studies is warranted.

Humans

Efficacy of tri-tab (T3 uptake diagnostic kit) under extreme temperature conditions.

A new surface adsorbent technique has been compared with the widely used resin sponge T3 uptake method. The new technique has the desired attributes, correlates very highly with the resin sponge method (r = 0.93) and has been accepted as a simple, rapid and reliable method under normal temperature conditions. However, under extreme conditions (0-20 degrees C and 30-60 degrees C) the test is unreliable.

Adolescent

Chemical and physical microenvironments at the Viking landing sites.

Physical and chemical considerations permit the division of the near-surface regolith on Mars into at least six zones of distinct microenvironments. The zones are euphotic, duricrust/peds, tempofrost, permafrost, endolithic, and interfacial/transitional. Microenvironments vary significantly in temperature extremes, mean temperature, salt content, relative pressure of water vapor, UV and visible light irradiance, and exposure to ionizing radiation events (100 Mrad) and oxidative molecular species. From what is known of the chemistry of the atmosphere and regolith fines (soil), limits upon the aqueous chemistry of soil pastes may be estimated. Heat of wetting could reach 45 cal/g dry soil; initial pH is indeterminate between 1 and 10; ionic strength and salinity are predicted to be extremely high; freezing point depression is inadequate to provide quantities of liquid water except in special cases. The prospects for biotic survival are grim by terrestrial standards, but the extremes of biological resiliency are inaccessible to evaluation. Second-generation in situ experiments which will better define Martian microenvironments are clearly possible. Antarctic dry valleys are approximations to Martian conditions, but deviate significantly by at least half-a-dozen criteria.

Chemical Phenomena

Metabolic adaptations in brown adipose tissue of the hamster in extreme ambient temperatures.

Cold acclimation caused the following changes in the brown adipose tissue (BAT) of the hamster: the relative weight of the tissue increased, it color darkened, the multilocular structure predominated, and tissue protein content increased while fat content decreased. There was also an increase in the mitochondrial protein content. Heat acclimation had the opposite effects, i.e., the color became lighter, total and mitochondrial protein decreased, fat content increased, and tissue structure was mostly unilocular. Accordingly, cold acclimation was accompanied by increased tissue respiration in the presence of chi-glycerophosphate (chi-GP) and succinate, whereas heat acclimation reduced the respiratory activity of the tissue with these substrates. Isolated BAT mitochondria from cold-acclimated animals increased activities of chi-GP and NADH oxidase, whereas the activities of succinic and cytochrome oxidases and the amount of mitochondrial cytochromes were unchanged. The effects of heat acclimation were more pronounced: there was a decrease in the activities of chi-GP, succinic, NADH, and cytochrome oxidases, as well as in the cytochrome a and a3 content. When respiration of tissue slices on succinate was compared to the maximal potential respiration, as measured with mitochondria disrupted by freezing and thawing, it was found that the relative activity (slices vs. disrupted mitochondria) was highest in cold-acclimated animals and decreased progressively with increasing acclimation temperatures. It is suggested that the differences in the apparent activity of the mitochondria were due to changes in the conformation of the mitochondria as a result of acclimation.

Acclimatization

The relationship between environmental temperature, cell growth and the fluidity and physical state of the membrane lipids in Bacillus stearothermophilus.

A definite and characteristic relationship exists between growth temperature, fatty acid composition and the fluidity and physical state of the membrane lipids in wild type Bacillus stearothermophilus. As the environmental temperature is increased, the proportion of saturated fatty acids found in the membrane lipids is also markedly increased with a concomitant decrease in the proportion of unsaturated and branched chain fatty acids. The temperature range over which the gel to liquid-crystalline membrane lipid phase transition occurs is thereby shifted such that the upper boundary of this transition always lies near (and usually below) the temperature of growth. This organism thus possesses an effective and sensitive homeoviscous adaptation mechanism which maintains a relatively constant degree of membrane lipid fluidity over a wide range of environmental temperatures. A mutant of B. stearothermophilus which has lost the ability to increase the proportion of relatively high melting fatty acids in the membrane lipids, and thereby increase the phase transition temperature in response to increases in environmental temperature, is also unable to grow at higher temperatures. An effective homeoviscous regulatory mechanism thus appears to extend the growth temperature range of the wild type organism and may be an essential feature of adaptation to temperature extremes. Over most of their growth temperature ranges the membrane lipids of wild type and temperature-sensitive B. stearothermophilus cells exist entirely or nearly entirely in the liquid-crystalline state. Also, the temperature-sensitive mutant is capable of growth at temperatures well above those at which the membrane lipid gel to liquid-crystalline phase transition is completed. Therefore, although other evidence suggests the existence of an upper limit on the degree of membrane fluidity compatible with cell growth, the phase transition is completed. Therefore, although other evidence suggests the existence of an upper limit on the degree of membrane fluidity compatible with cell growth, the phase transition upper boundary itself does not directly determine the maximum growth temperature of this organism. Similarly, the lower boundary does not determine the minimum growth temperature, since cell growth ceases at a temperature at which most of the membrane lipid still exists in a fluid state. These observations do not support the suggestion made in an earlier study, which utilized electron spin resonance spectroscopy to monitor membrane lipid lateral phase separations, that the minimum and maximum growth temperatures of this organism might directly be determined by the solid-fluid membrane lipid phase transition boundaries. Evidence is presented here that the electron spin resonance techniques used previously did not in fact detect the gel to liquid-crystalline phase transition of the bulk membrane lipids, which, however, can be reliably measured by differential thermal analysis.

Cell Division

Plant nitrogen nutrition: enhancing plant resilience to abiotic stresses.

Nitrogen (N) is not only an essential macronutrient for plant growth and development but also functions as a pivotal signaling molecule that orchestrates adaptive responses to various abiotic stresses, including acidic stress, aluminum toxicity, salinity, drought, and extreme temperatures. This review synthesizes recent advances in our understanding of the molecular mechanisms by which N signaling, mediated by different N forms (e.g., NH4+ and NO3-), integrates with core stress-response pathways. We specifically discuss the genetic crosstalk between N sensing and key signaling cascades, including abscisic acid (ABA) signaling, the salt overly sensitive (SOS) pathway, and reactive oxygen species (ROS) homeostasis. The review details how this integration modulates physiological and transcriptional reprogramming through central regulators such as NIN-like proteins (NLPs), calcineurin B-like protein (CBL)-interacting protein kinase (CIPK), and the target of rapamycin (TOR) kinase, ultimately optimizing the trade-off between growth and tolerance. By establishing a unified genetic and molecular framework, this review aims to provide a theoretical basis for developing novel strategies in precision N management and molecular breeding to synergistically enhance N use efficiency (NUE) and abiotic stress tolerance in crops.

Nitrogen

Changes in membrane lipid composition during temperature adaptation by a thermotolerant strain of Tetrahymena pyriformis.

Experiments on temperature adaptation have been conducted using a thermotolerant clone of Tetrahymena pyriformis designated as strain NT-1. The strain was able to grow well at 39.5 and 15 degrees C and could adapt quickly when transferred from one of these temperatures to the other. Cells grown at the extreme temperatures differed markedly in their membrane lipid composition, particularly in the phospholipid polar head groups and hydrocarbon chains. The levels of fatty acid unsaturation increased at the lower temperature (e.g. 15 degrees C cells contained 31% gamma-linolenic acid vs. 25% at 39.5 degrees C) as did the content of alkyl glyceryl ether derivatives. Ethanolamine phosphoglycerides decreased by more than 10 mol % of the lipid phosphorus with the drop in temperature, the decrease being offset by a concomitant rise in 2-aminoethylphosphonolipid. These temperature-induced changes were noted in certain purified membrane preparations as well as in whole cells. Experiments with [14C]palmitic acid and sodium[14C]acetate showed that fatty acids are first incorporated into phospholipids predominantly in a saturated form. The membranes served as a reservoir of fatty acid substrate for desaturase activity. Tetrahymena pyriformis, strain NT-1, was proposed as a useful model system for studying the temperature adaptation process in eukaryotic cells.

Acclimatization

Responses to temperate, cold, and hot environments and the effect of physical training.

Ten young men underwent several tests before and after a training program: a bicycle ergometer test and 60 min of moderate exercise performed at a temperate 24 degrees C; the same work load performed in heat (40.0 degrees C DB, 30.4 degrees C WB) for 3 h; and cold (10 degrees C) exposure for 60 min. Training consisted of 13 1-h sessions of hard, strenuous, and exhaustive work performed in temperate conditions four times a week. Training resulted in substantial decreases in heart rate and rectal temperature responses to exercise in temperate, minor increases in hot, and no significant changes in cold conditions. Subjects who showed good responses to heat, also showed good responses at 24 degrees C, and poor compensatory responses to cold, which were indicated by relatively low heat production and rectal temperature values, and relatively high body heat loss and extremities temperature values. Subjects who showed poor heat tolerance also showed poor responses in temperate and good compensatory responses in cold conditions. Positive correlation coefficients were found between rectal temperatures in the three environments, and between heart rate and sweat rate responses in temperate and hot conditions. The results indicated that moderately severe training causes minor tolerance improvements in heat and no changes in cold, and that responses in temperate, cold, and hot environments are interdependent.

Acclimatization

Transcriptomic characterization of the intestine in Stichopus monotuberculatus under gradient temperature stress and HSP gene family-mediated molecular adaptation.

The increasing frequency of extreme temperature events under climate change poses a growing threat to the stability of tropical sea cucumber aquaculture. To characterize the molecular responses of the tropical sea cucumber Stichopus monotuberculatus to acute temperature stress, juveniles were exposed for 96&#xa0;h to 15&#xa0;&#xb0;C, 20&#xa0;&#xb0;C, 25&#xa0;&#xb0;C, 30&#xa0;&#xb0;C, and 35&#xa0;&#xb0;C, followed by transcriptomic profiling of the intestine. By transcriptomic analysis, 2258, 634, 1618, and 2980 differentially expressed genes (DEGs) were identified at 15, 20, 30, and 35&#xa0;&#xb0;C compared to control, respectively. More DEGs were generally detected at temperatures further from 25&#xa0;&#xb0;C, with the 35&#xa0;&#xb0;C group showing the largest transcriptional response. Although cold and heat stress both affected metabolism and protein homeostasis, their enrichment profiles differed. At 15&#xa0;&#xb0;C, DEGs were mainly enriched in the spliceosome and p53 signaling pathways, highlighting RNA processing and p53 signaling as prominent features of the cold-stress response. At 35&#xa0;&#xb0;C, DEGs were mainly enriched in the PI3K-Akt signaling pathway, ubiquitin-mediated proteolysis, and mitophagy, indicating enhanced regulation of cell survival, protein turnover, and mitochondrial quality control. HSP genes also responded differently to cold and heat stress. Most HSP70 and HSP90 family members were downregulated at low temperatures, whereas HSP70 genes and small heat shock proteins were markedly upregulated at high temperatures. Overall, the intestinal transcriptome showed distinct responses to cold and heat stress. These results identify pathways and HSP genes potentially involved in the temperature response of S. monotuberculatus and provide useful information for evaluating temperature tolerance and defining suitable temperatures for its aquaculture.

Heat shock protein

[Dynamics of transcallosal potentials following local exposure of the cerebral cortex to high temperature].

Experiments were conducted on cats, anesthetized with nembutal. The influence of local heating of the sensomotor cortex on the transcallosum response was examined. It was revealed that heating for short and long periods of limited regions of the cortex of both hemispheres induced a primary depression of the negative component of the transcallosum response at 44 degrees C and above it. The depression was replaced by an irreversible block of both response phases at 47--49 degrees C. It was concluded that the direct inhibitory influence of high temperatures on the cortical neurons was expressed only within the range of extreme temperature incompatible with vital activity of the whole organism. Experiments with the thermal block of the hemisphere region could testify to the fact that the transcallosum responses occurred mainly as a result of the direct irritation of the callosum fibers by stimulating electrodes and entirely reflected the post-synaptic potentials.

Animals

Expansion of the functional genomics GRACE library reveals genes relevant for temperature-dependent fitness in Candida albicans.

A small percentage of species in the fungal kingdom can cause devastating infections in humans, with Candida albicans reigning as a leading cause of systemic disease. One of the key virulence phenotypes for pathogenic fungi is the ability to survive at host body temperature; however, a comprehensive understanding of the mechanisms that orchestrate thermal adaptation in fungi remains incomplete. In this study, we expand the largest functional genomics resource in C. albicans, reaching 71.3% coverage of the entire genome, and perform screens under six different temperatures to identify genes important for temperature-dependent fitness. We describe the function of genes involved in translation (GAR1), splicing (C1_11680C or YSF3), and cell cycle progression (C6_00110C or RHT1) in enabling fungal survival at both low and high temperatures. Through experimental evolution, we also show that C. albicans can rapidly overcome deleterious mutations and adapt to extreme temperature environments. Overall, our study highlights the transformative potential of genome-wide functional genomics to uncover critical vulnerabilities in pathogenic fungi.

Genomics

Mutations in the structural genes of CHO cell histidyl-, valyl-, and leucyl-tRNA synthetases.

Forty-three temperature-sensitive mutants were isolated in the CHO cell line by selecting for noncycling cells using [3H]TdR and cytosine arabinoside. Cell division was extremely temperature sensitive in eight of the mutants, and these were studied in more detail. In seven of these eight mutants, the in vitro specific activity of a single aminoacyl-tRNA synthetase was greatly reduced; four had reduced levels of histidyl-tRNA synthetase, two of valyl-tRNA synthetase, and one of leucyl-tRNA synthetase. Cell hybridization studies showed that the mutants formed three complementation groups. In six of the seven mutants the aminoacyl-tRNA synthetase which had reduced activity was also more thermolabile than the wild-type enzyme. The spontaneous reversion frequency was low for these mutants, and in most cases could be increased by treatment with a chemical mutagen. The isolation of the valyl-tRNA synthetase mutant reported here brings to eight the number of different aminoacyl-tRNA synthetase mutants isolated in the CHO cell line.

Amino Acyl-tRNA Synthetases

DNA synthesis by hybrid echinoid embryos produced from parent species of low and high temperature tolerance.

Synthesis of DNA, as measured by quantitative Feulgen microspectrophotometry, was studied in reciprocal echinoid hybrids and their homospermic controls. Both parent species develop at the same rate until hatching, at 20 degrees C. One parent (Lytechinus) will develop normally at 25 degrees C, a temperature lethal for the other parent employed in the studies (Strongylocentrotus). Strongylocentrotus will develop normally at 10 degrees C, a temperature at which Lytechinus fertilised eggs live, but fail to cleave. It was found that sperm of Lytechinus in eggs of Strongylocentrotus (SL hybrid) show a slowing of the S phase of the cell cycle at 10 degrees C, and that sperm of Strongylocentrotus in eggs of Lytechinus (LS hybrid) show a slowing of the S phase at 25 degrees C. These slowing effects are not noted during cleavage stages. The results are discussed in terms of proteins produced during the time of active transcription of the hybrid genome which may be rate-limiting in the synthesis of DNA in the hybrid embryos under these temperature extremes.

Animals

Purification and properties of histidinol dehydrogenases from psychrophilic, mesophilic and thermophilic bacilli.

As a first step in elucidating one molecular mechanism of adaptation to life at extreme temperatures, we purified and characterized the enzyme histidinol dehydrogenase (EC 1.1.1.23) from a number of bacilli whose growth temperatures range from 5 degrees t to 90 degrees C. The enzymes were purified by (NH4)2SO4 precipitation, ion-exchange chromatography on Sephadex, affinity chromatography on histamine- or histidine-Sepharose and preparative gradient gel electrophoresis. All had similar mol.wts. (29200), sedimentation coefficients (S20,w 2.56S), affinities for histidinol and NAD+ (Km = 48 micron and 0.2 mM respectively) and all had pH optima at 9.6. Marked differences were observed in stability with respect to temperature and the temperature at which the initial velocity for histidinol dehydrogenation was optimal. These optima range from 25 degrees C for the enzyme from the psychrophilic species through to 41 degrees C for the mesophiles to 85-92 degrees C for the extreme thermophiles. It is concluded that the ability of the enzymes to operate at their various optimum temperatures is an intrinsic property of their amino acid sequences.

Alcohol Oxidoreductases

Relation of general activity in rats to environmental temperature.

The relation between ambient temperature and amount and pattern of wheel running was examined in four experiments, with a total of 88 adult male albino rats of the Sprague-Dawley strain, under conditions of 12-hr. light/12-hr. dark. While lowering of temperature from baseline of 21--25 degrees C to 4--7 degrees C most typically led to increased running, consistently reduced running characterized a substantial number of individuals, especially those with relatively high baseline scores. When comparison trials were run at 27 degrees C, reduced activity was recorded for virtually all subjects. As temperature was elevated above 27 degrees C, however, there was in most cases an upturn. At 34 degrees C, 24-hr. running scores tended to exceed baseline level for about half the animals, and running during the light 12 hr. of the day was above baseline for virtually all. Analysis of the temporal distribution suggests that the thermoregulatory reduction of activity, readily demonstrated at the moderately warm temperature, is complicated by efforts to escape as the environment becomes aversively hot. Failure of previous investigators to observe this is attributable in part to apparatus and recording differences. It is speculated that the pattern of response to extreme temperatures is closely related to the circadian fluctuation of internal temperature.

Animals

Thermostability at ultrahigh temperatures of thermolysin and a protease from a psychrotrophic Pseudomonas.

Thermal inactivation at 110-150 degrees C of thermolysin (EC 3.4.24.4), produced by the thermophile Bacillus thermoproteolyticus, and the extracellular protease of Pseudomonas sp. MC60 a psychotroph, were investigated at 130 degrees C, both enzymes had approximately the same deltaH (22 kcal/mol) and deltaS (-13.5 cal/mol per degree) values. Both enzymes contain zinc and calcium. The amino acid compositions of the enzymes were similar except that MC60 protease exhibited a more typical tyrosine content. Comparable heat resistance at extreme temperatures of enzyme produced by psychrotrophic and thermophilic organisms emphasizes the difference between molecular properties that resist denaturation at elevated temperatures and those that allow reversible denaturation.

Amino Acids

Effect of environmental temperature stress on intramammary infections of dairy cows and monitoring of body and intramammary temperatures by radiotelemetry.

Four dairy cows were stressed by exposure to hot and cold environments in tests to determine the effect of environment on milk yield, somatic cell counts, and California mastitis test scores of milk from all mammary quarters and on bacterial counts of milk from infected quarters. Two cows were held in temperature-controlled rooms for successive 5-day periods at moderate (21 to 28 C), cold (-16 C), moderate, hot (36 to 37 C), and moderate environments. The cold and hot sequences were reversed for the other 2 cows. Temperature transmitters were surgically implanted in the skeletal muscles of the loin and gluteal regions; however, only one of these transmitters (gluteal region) functioned continuously throughout the experiment. At the end of this experiment, a transmitter was implanted in the gland cistern of a rear quarter of 1 cow, and the sequence of holding in the cold before the hot environment was used. Mean body temperature was approximately 1 degree higher (39.2 C) in the hot room (1 cow) and 3 to 4 degrees lower (35 C and 33 C), respectively, for 2 cows) in the cold room than that during the moderate temperature periods. A similar comparison showed that the mean intramammary temperature was 1 to 2 degrees higher (39.5 C) in the hot room and approximately 9 degrees lower (29.4 C) in the cold room. Exposure of the cows to hot and cold environments caused a greater loss in milk production in the 2 medium-yielding cows (23 to 28 kg/day) than in the 2 low-yielding cows (9 to 13 kg/day). The effect of the extreme temperatures on the somatic cell counts in uninfected quarters was limited to only a few quarters and was inconsistent (mean counts increased and decreased at both temperatures). The California mastitis test reactions showed no consistent changes during periods of heat and cold stress. Also, the effect of the environmental temperature on the intramammary infections also was inconsistent. The effect on bacterial counts appeared to vary with the type of organism. Some mean counts decreased in the heat and cold (Streptococcus agalactiae, Micrococcus sp), some increased (Pseudomonas sp), and another seemed independent (Streptococcus uberis) of the environmental temperature at which the cow was held.

Animals