Cold Exposure Research Articles

TLCD4 as Potential Transcriptomic Biomarker of Cold Exposure.

(1) Background: Cold exposure induces metabolic adaptations that can promote health benefits, including increased energy disposal due to lipid mobilization in adipose tissue (AT). This study aims to identify easily measurable biomarkers mirroring the effect of cold exposure on AT. (2) Methods: Transcriptomic analysis was performed in peripheral blood mononuclear cells (PBMCs) and distinct AT depots of two animal models (ferrets and rats) exposed to cold, and in PBMCs of cold-exposed humans. (3) Results: One week of cold exposure (at 4 °C) affected different metabolic pathways and gene expression in the AT of ferrets, an animal model with an AT more similar to humans than that of rodents. However, only one gene, Tlcd4, was affected in the same way (overexpressed) in aortic perivascular and inguinal AT depots and in PBMCs, making it a potential biomarker of interest. Subsequent targeted analysis in rats showed that 1 week at 4 °C also induced Tlcd4 expression in brown AT and PBMCs, while 1 h at 4 °C resulted in reduced Tlcd4 mRNA levels in retroperitoneal white AT. In humans, no clear effects were observed. Nevertheless, decreased PBMC TLCD4 expression was observed after acute cold exposure in women with normal weight, although this effect could be attributed to short-term fasting during the procedure. No effect was evident in women with overweight or in normal-weight men. (4) Conclusions: Our results obtained for different species point toward TLCD4 gene expression as a potential biomarker of cold exposure/fat mobilization that could tentatively be used to address the effectiveness of cold exposure-mimicking therapies.

Effects of climate change on seed germination may contribute to habitat homogenization in freshwater forested wetlands

Climate changes in temperate regions are expected to result in warmer, shorter winters in temperate latitudes. These changes may have consequences for germination of plant species that require a period of physiological dormancy. The effect of cold duration on seed germination has been investigated in a number of plant taxa, but has not been well studied in wetland and bottomland forest tree species, an ecosystem that is threatened by habitat homogenization. Our work sought to test the role of changing winter temperatures on seed germination in specialist (Nyssa aquatica and Taxodium distichum) and generalist (Acer rubrum and Liquidambar styraciflua) tree species within forested wetlands throughout the eastern U.S. The experiment was conducted in an environmental chamber in Norfolk, VA, USA. Seeds of T. distichum, N. aquatica, A. rubrum, and L. styraciflua were exposed to each of seven pre-germination cold exposure durations (0, 15, 30, 45, 60, 75, and 90 days) and observed for germination for 30 days. Cold stratification duration positively impacted total percent germination in N. aquatica (p < 0.0001) as well as A. rubrum (p = 0.0008) and T. distichum (p = 0.05). Liquidambar styraciflua seeds exhibited more rapid rates of germination with increasing cold exposure duration and greater percent germination compared to the others regardless of cold stratification duration. Our results provide insight into how community dynamics and biodiversity of wetland and bottomland trees may shift with a changing climate. Further, this work emphasizes the importance of understanding the role of plant functional traits in early life stages in community dynamics and has implications for management practices.

Effect of Cold Temperature on the Severity of Allergic Rhinitis Based on Visual Analog Scale (VAS) Score Among Medical Students of Malikussaleh University

BACKGROUND: Allergic rhinitis is a common condition caused by inflammation of the nasal mucosa after exposure to allergens and is mediated by Immunoglobulin E (IgE). Cold temperatures can aggravate the symptoms of allergic rhinitis. Allergic rhinitis is not fatal, but it can cause a decrease in the patient's quality of life if the symptoms are severe. The severity of allergic rhinitis symptoms is difficult to measure as it should match patient's perception, so VAS is a quantitative measurement tool used. Although VAS is a simple and easy-to-use tool, its use as self-monitoring for AR patients is still infrequent to minimize symptom exacerbations and maintain control of allergic rhinitis. AIMS: This study aims to examine the effect of cold temperature on the severity of allergic rhinitis based on VAS score. METHOD: This research is an experimental with a one-group pretest-posttest study. The study samples involved 75 students suffering from allergic rhinitis assessed with the Score for Allergic Rhinitis (SFAR) questionnaire assessment from the class of 2020, 2021, and 2022. Subjects’ pain level was measured before and after the intervention. The intervention was in the form of cold temperature exposure for 15 minutes in a room with a temperature of 18℃. Data were analyzed using the Wilcoxon test. RESULT: The results showed that the mean VAS score before the intervention was 0 while after the intervention was 38.61 ± 24.07. This shows that the mean VAS score after the intervention is higher than the mean VAS score before the intervention (p-value = 0.00 &lt;0.05). CONCLUSION: The results of this study indicate that the effect of cold temperature can increase the severity of allergic rhinitis.

Chronic cold stress promotes inflammation and ER stress via inhibiting GLP-1R signaling, and exacerbates the risk of ferroptosis in the liver and pancreas

The cold climates in autumn and winter threatens human health. The aim of this study was to reveal the effects of prolonged cold exposure on the liver and pancreas based on GLP-1R signaling, oxidative stress, endoplasmic reticulum (ER) stress and ferroptosis by Yorkshire pig models. Yorkshire pigs were divided into the control group and chronic cold stress (CCS) group. The results showed that CCS induced oxidative stress injury, activated Nrf2 pathway and inhibited the expression of GLP-1R in the liver and pancreas (P < 0.05). The toll-like receptor 4 (TLR4) pathway was activated in the liver and pancreas, accompanied by the enrichment of IL-1β and TNF-α during CCS (P < 0.05). Moreover, the kinase RNA-like endoplasmic reticulum kinase (PERK), inositol requiring kinase 1 (IRE1), X-box-binding protein 1 (XBP1) and eukaryotic initiation factor 2α (eIF2α) expression in the liver and pancreas was up-regulated during CCS (P < 0.05). In addition, CCS promoted the prostaglandin-endoperoxide synthase 2 (PTGS2) expression and inhibited the ferritin H (FtH) expression in the liver. Summarily, CCS promotes inflammation, ER stress and apoptosis by inhibiting the GLP-1R signaling and inducing oxidative stress, and exacerbates the risk of ferroptosis in the liver and pancreas.

Brown fat-specific mitoribosomal function is crucial for preventing cold exposure-induced bone loss

This study examines the interplay between ambient temperature, brown adipose tissue (BAT) function, and bone metabolism, emphasizing the effects of cold exposure and BAT mitochondrial activity on bone health. Utilizing ovariectomized (OVX) mice to model primary osteoporosis and BAT-specific mitochondrial dysfunction (BKO) mice, we evaluated the impact of housing temperature on bone density, immune modulation in bone marrow, and the protective role of BAT against bone loss. Cold exposure was found to universally reduce bone mass, enhance osteoclastogenesis, and alter bone marrow T-cell populations, implicating the immune system in bone remodeling under cold stress. The thermogenic function of BAT, driven by mitochondrial oxidative phosphorylation, was crucial in protecting against bone loss. Impaired BAT function, through surgical removal or mitochondrial dysfunction, exacerbated bone loss in cold environments, highlighting BAT’s metabolic role in maintaining bone health. Furthermore, cold-induced changes in BAT function led to systemic metabolic shifts, including elevated long-chain fatty acids, which influenced osteoclast differentiation and activity. These findings suggest a systemic mechanism connecting environmental temperature and BAT metabolism with bone physiology, providing new insights into the metabolic and environmental determinants of bone health. Future research could lead to novel bone disease therapies targeting these pathways.

Adipogenin Dictates Adipose Tissue Expansion by Facilitating the Assembly of a Dodecameric Seipin Complex.

Adipogenin (Adig) is an evolutionarily conserved microprotein and is highly expressed in adipose tissues and testis. Here, we identify Adig as a critical regulator for lipid droplet formation in adipocytes. We determine that Adig interacts directly with seipin, leading to the formation of a rigid complex. We solve the structure of the seipin/Adig complex by Cryo-EM at 2.98Å overall resolution. Surprisingly, seipin can form two unique oligomers, undecamers and dodecamers. Adig selectively binds to the dodecameric seipin complex. We further find that Adig promotes seipin assembly by stabilizing and bridging adjacent seipin subunits. Functionally, Adig plays a key role in generating lipid droplets in adipocytes. In mice, inducible overexpression of Adig in adipocytes substantially increases fat mass, with enlarged lipid droplets. It also elevates thermogenesis during cold exposure. In contrast, inducible adipocyte-specific Adig knockout mice manifest aberrant lipid droplet formation in brown adipose tissues and impaired cold tolerance.

Physiological Features of the Response of the Respiratory and Circulation Systems to Physical Load in Students Engaged in Winter Football

Adaptive changes in the circulatory and respiratory systems under the influence of winter football training were studied. 50 men aged 21-25 years — 3rd-4th year students — were examined: control group — 25 people specializing in “soccer” (S), main group — 25 people studying in the specialization “winter football” (WF). The examination was performed twice — before and after physical activity. Running (average pace, 180 steps/min) for 15 minutes was used as dosed physical activity. The loads were performed either indoors at a temperature of plus 22–24°C, or in winter outside at a temperature of minus 18–20°C. Indoor and outdoor surveys were carried out on different days. Assessment of peripheral blood flow in the lower extremities was performed using rheography; to assess the main blood flow in the femoral artery, Doppler ultrasound was used. The study of external respiration functions was carried out using pneumotachography. The lactate concentration in capillary blood was determined photometrically. It has been shown that physical activity performed in the cold in adapted athletes (WF group) promotes increased integration between the respiratory and circulatory systems, ensuring the formation of a functional system characterized by stronger connections for optimal adaptation to the combined effects of physical activity and cold. In athletes training indoors (group S) under conditions of a combination of physical activity and cold exposure, on the contrary, desynchronization of the interaction of the respiratory and circulatory systems occurs, which leads to a decrease in adaptive reserves. Thus, sports training in winter football triggers phenotypic adaptive changes and creates a number of physiological mechanisms that promote increased integration between the respiratory and circulatory systems, providing optimal adaptation to the combined effects of physical activity and cold. The obtained facts will be useful for the development of special training programs aimed at increasing the functional reserve of the cardiorespiratory system of athletes training in cold conditions.

Comparative transcriptomic profiles of Paulownia catalpifolia under different degrees of chilling stress during the seedling stage

BackgroundPaulownia, an ecologically and economically valuable plant species native to China, is notable for its excellent timber quality and strong adaptability. Among them, Paulownia catalpifolia displays the ability to survive in cold climate, a trait associated with northern China. Yet, the molecular information for its cold-tolerance has not been explored. This study was to investigate the changes in physiological indices and transcript levels of P. catalpifolia following cold exposure, which could provide evidence for revealing whether there were differences in the genetic basis of inducing physiological perturbations between moderate low temperature (MLT) and extreme low temperature (ELT).ResultsThe detection of physiological indices under diverse degrees of chilling stress showed similar patterns of alteration. Enhanced accumulation of osmoregulatory substances, such as soluble sugar and soluble protein, were more conducive under ELT compared to MLT in P. catalpifolia. Moreover, we observed leaf wilting symptoms distinctly after exposure to ELT for 48 h, while this effect was not obvious after MLT exposure for 48 h. Comparative transcriptomic analysis between MLT and ELT demonstrated 13,688 differentially expressed genes (DEGs), most of them appeared after 12 h and 48 h of treatment. GO and KEGG analyses elucidated prominent enrichment in aromatic-L-amino-acid decarboxylase activity term and carbohydrate metabolism pathways. Therefore, it was speculated that the DEGs involved in the above processes might be related to the difference in the contents of soluble protein and soluble sugar between MLT and ELT. Time series clustering analyses further highlighted several key genes engaged in the ‘Glycosyltransferases’, ‘Galactose metabolism’ and ‘Starch and sucrose metabolism’ pathways as well as the ‘tyrosine decarboxylase activity’ term. For instance, cellulose synthase-like A (CLSA2/9), raffinose synthase (RafS2), β-amylase (BAM1) and tyrosine/DOPA decarboxylase (TYDC1/2/5) genes, diverging in their expression trends between MLT and ELT, might significantly affect the soluble sugar and soluble protein abundance within P. catalpifolia.ConclusionBetween MLT and ELT treatments, partial overlaps in response pathways of P. catalpifolia were identified, while several genes regulating the accumulation of osmotic adjustment substances had disparate expression patterns. These findings could provide a novel physiological and molecular perspective for P. catalpifolia to adapt to complex low temperature habitats.

Hyaluronan Mediates Cold-Induced Adipose Tissue Beiging.

Adipose tissue beiging refers to the process by which beige adipocytes emerge in classical white adipose tissue depots. Beige adipocytes dissipate chemical energy and secrete adipokines, such as classical brown adipocytes, to improve systemic metabolism, which is beneficial for people with obesity and metabolic diseases. Cold exposure and β3-adrenergic receptor (AR) agonist treatment are two commonly used stimuli for increasing beige adipocytes in mice; however, their underlying biological processes are different. Transcriptional analysis of inguinal white adipose tissue (iWAT) has revealed that changes in extracellular matrix (ECM) pathway genes are specific to cold exposure. Hyaluronic acid (HA), a non-sulfated linear polysaccharide produced by nearly all cells, is one of the most common components of ECM. We found that cold exposure significantly increased iWAT HA levels, whereas the β3-AR agonist CL316,243 did not. Increasing HA levels in iWAT by Has2 overexpression significantly increases cold-induced adipose tissue beiging; in contrast, decreasing HA by Spam1 overexpression, which encodes a hyaluronidase that digests HA, significantly decreases cold-induced iWAT beiging. All these data implicate a role of HA in promoting adipose tissue beiging, which is unique to cold exposure. Given the failure of β3-AR agonists in clinical trials for obesity and metabolic diseases, increasing HA could serve as a new approach for recruiting more beige adipocytes to combat metabolic diseases.

Freezing-induced anaesthesia in Cornu aspersum (Müller 1774): a potential method

ABSTRACT A convenient and acceptable method of anaesthetisation is still unresolved in gastropods, particularly Cornu aspersum. The aim of this study was to determine the anaesthetic effects of freezing at −20°C for different periods, including 5, 10, 15, 20, 25, 30, 45, 60, 120, 180 and 240 min on C. aspersum. Following cold treatments, the snails were checked for anaesthesia and recovery behaviours using a 5-score evaluation based on the responses at 0, 5, 10, 15, 20, 25, 30, 45, 60, 120, 180, 240, 1440 and 2880 min. The responses evaluated were reflex, movement, mucus secretion and survival. The results showed that 60 min of cold exposure was stressful and that longer periods of freezing than this treatment were lethal for C. aspersum. The results indicate that the optimum duration of freezing for a desired anaesthesia evaluated based on the reflex and movement responses is 10 min.

Seasonal dynamics of small mammal populations: resource availability and cold exposure interact to govern abundance

Seasonal dynamics of small mammal populations: resource availability and cold exposure interact to govern abundance

Occurrence of Wetness on the Fruit Surface Modeled Using Spatio-Temporal Temperature Data from Sweet Cherry Tree Canopies

Typically, fruit cracking in sweet cherry is associated with the occurrence of free water at the fruit surface level due to direct (rain and fog) and indirect (cold exposure and dew) mechanisms. Recent advances in close range remote sensing have enabled the monitoring of the temperature distribution with high spatial resolution based on light detection and ranging (LiDAR) and thermal imaging. The fusion of LiDAR-derived geometric 3D point clouds and merged thermal data provides spatially resolved temperature data at the fruit level as LiDAR 4D point clouds. This paper aimed to investigate the thermal behavior of sweet cherry canopies using this new method with emphasis on the surface temperature of fruit around the dew point. Sweet cherry trees were stored in a cold chamber (6 °C) and subsequently scanned at different time intervals at room temperature. A total of 62 sweet cherry LiDAR 4D point clouds were identified. The estimated temperature distribution was validated by means of manual reference readings (n = 40), where average R2 values of 0.70 and 0.94 were found for ideal and real scenarios, respectively. The canopy density was estimated using the ratio of the number of LiDAR points of fruit related to the canopy. The occurrence of wetness on the surface of sweet cherry was visually assessed and compared to an estimated dew point (Ydew) index. At mean Ydew of 1.17, no wetness was observed on the fruit surface. The canopy density ratio had a marginal impact on the thermal kinetics and the occurrence of wetness on the surface of sweet cherry in the slender spindle tree architecture. The modelling of fruit surface wetness based on estimated fruit temperature distribution can support ecophysiological studies on tree architectures considering resilience against climate change and in studies on physiological disorders of fruit.

Kinin B1 receptor deficiency promotes enhanced adipose tissue thermogenic response to β3-adrenergic stimulation.

Kinin B1 receptor (B1R) has a key role in adipocytes to protect against obesity and glycemic metabolism, thus becoming a potential target for regulation of energy metabolism and adipose tissue thermogenesis. Kinin B1 knockout mice (B1KO) were subjected to acute induction with CL 316,243 and chronic cold exposure. Metabolic and histological analyses, gene and protein expression and RNA-seq were performed on interscapular brown adipose tissue (iBAT) and inguinal white adipose tissue (iWAT) of mice. B1KO mice, under acute effect of CL 316,243, exhibited increased energy expenditure and upregulated thermogenic genes in iWAT. They were also protected from chronic cold, showing enhanced non-shivering thermogenesis with increased iBAT mass (~ 90%) and recruitment of beige adipocytes in iWAT (~ 50%). Positive modulation of thermogenic and electron transport chain genes, reaching a 14.5-fold increase for Ucp1 in iWAT. RNA-seq revealed activation of the insulin signaling pathways for iBAT and oxidative phosphorylation, tricarboxylic acid cycle, and browning pathways for iWAT. B1R deficiency induced metabolic and gene expression alterations in adipose tissue, activating thermogenic pathways and increasing energy metabolism. B1R antagonists emerge as promising therapeutic targets for regulating obesity and associated metabolic disorders, such as inflammation and diabetes.

SMYD5 is a regulator of the mild hypothermia response.

The mild hypothermia response (MHR) maintains organismal homeostasis during cold exposure and is thought to be critical for the neuroprotection documented with therapeutic hypothermia. To date, little is known about the transcriptional regulation of the MHR. We utilize a forward CRISPR-Cas9 mutagenesis screen to identify the histone lysine methyltransferase SMYD5 as a regulator of the MHR. SMYD5 represses the key MHR gene SP1 at euthermia. This repression correlates with temperature-dependent levels of H3K36me3 at the SP1-locus and globally, indicating that the mammalian MHR is regulated at the level of histone modifications. We have identified 37 additional SMYD5 regulated temperature-dependent genes, suggesting a broader MHR-related role for SMYD5. Our study provides an example of how histone modifications integrate environmental cues into the genetic circuitry of mammalian cells and provides insights that may yield therapeutic avenues for neuroprotection after catastrophic events.

Unveiling the translational dynamics of lychee (Litchi chinesis Sonn.) in response to cold stress

Cold stress poses a significant threat to the quality and productivity of lychee (Litchi chinensis Sonn.). While previous research has extensively explored the genomic and transcriptomic responses to cold stress in lychee, the translatome has not been thoroughly investigated. This study delves into the translatomic landscape of the 'Xiangjinfeng' cultivar under both control and low-temperature conditions using RNA sequencing and ribosome profiling. We uncovered a significant divergence between the transcriptomic and translatomic responses to cold exposure. Additionally, bioinformatics analyses underscored the crucial role of codon occupancy in lychee's cold tolerance mechanisms. Our findings reveal that the modulation of translation via codon occupancy is a vital strategy to abiotic stress. Specifically, the study identifies ribosome stalling, particularly at the E site AAU codon, as a key element of the translation machinery in lychee's response to cold stress. This work enhances our understanding of the molecular dynamics of lychee's reaction to cold stress and emphasizes the essential role of translational regulation in the plant's environmental adaptability.

Risk assessment models for development of carpal tunnel syndrome: clinical, anthropometric, and neuromuscular ultrasound predictors

BackgroundCarpal tunnel syndrome (CTS) is the most common entrapment neuropathy with multifactorial etiologies. We intended in this case–control study to identify, out of a comprehensive set of risk factors, the relatively important ones and develop a quantitative risk assessment model for this disorder. It was also legitimate to define the hazard of those factors in a dose-related manner and the acceptable safe limit especially for work-related stresses.ResultsAge and female predominance were comparable between the 60 patients (89 hands with electrophysiologically confirmed CTS) and 50 controls (100 hands). Occupation of the studied sample varied between housewives only, employed housewives, and manual workers with a distribution that differed significantly between patients and controls. Significantly higher body mass index (BMI) and mean wrist depth were found in patients than controls. Wrist ratio (clinically or sonographically) was significantly squarer in patients than controls. Overall workload and number of hours spent daily performing work with repeated hand movements or awkward hand position were significantly higher among patients than controls.ROC curves were constructed for wrist measurements and occupational stresses. Cut-off points of wrist ratio and internal carpal tunnel ratio (by ultrasound) to discriminate subjects with CTS were > 0.68 and ≤ 1.854, respectively. The best cut-off value for number of hours spent daily performing work with repeated hand movements was 3 h/ day. As for working with awkward hand position or cold exposure, cut-off value was 0.6 h/day for both.Two logistic regression models were conducted to investigate nonoccupational and occupational predictors of CTS. The independent predictors concluded from the first model were BMI, positive family history of CTS, wrist ratio, and decrease grip strength. As for the occupational model, predictors were tasks requiring awkward hand position and cold exposure.ConclusionOccupational risk assessment by clinical, anthropometric, and ultrasonographic measurement should be used in professions requiring repetitive or awkward hand movements, so that in overweight persons with square wrists appropriate workplace setup measures or assistive technology at work or home could be taken to prevent or decrease the impact of work hazards or help choose individuals with low risk for appropriate jobs.

Immune response to cold exposure: Role of γδ T cells and TLR2-mediated inflammation.

The mammalian body possesses remarkable adaptability to cold exposure, involving intricate adjustments in cellular metabolism, ultimately leading to thermogenesis. However, cold-induced stress can impact immune response, primarily through noradrenaline-mediated pathways. In our study, we utilized a rat model subjected to short-term or long-term mild cold exposure to investigate systemic immune response during the cold acclimation. To provide human relevance, we included a group of regular cold swimmers in our study. Our research revealed complex relationship between cold exposure, neural signaling, immune response, and thermogenic regulation. One-day cold exposure triggered stress response, including cytokine production in white adipose tissue, subsequently activating brown adipose tissue, and inducing thermogenesis. We further studied systemic immune response, including the proportion of leukocytes and cytokines production. Interestingly, γδ T cells emerged as possible regulators in the broader systemic response, suggesting their possible contribution in the dynamic process of cold adaptation. We employed RNA-seq to gain further insights into the mechanisms by which γδ T cells participate in the response to cold. Additionally, we challenged rats exposed to cold with the Toll-like receptor 2 agonist, showing significant modulation of immune response. These findings significantly contribute to understanding of the physiological acclimation that occur in response to cold exposure.

Distinct roles of H3K27me3 and H3K36me3 in vernalization response, maintenance, and resetting in winter wheat.

Winter plants rely on vernalization, a crucial process for adapting to cold conditions and ensuring successful reproduction. However, understanding the role of histone modifications in guiding the vernalization process in winter wheat remains limited. In this study, we investigated the transcriptome and chromatin dynamics in the shoot apex throughout the life cycle of winter wheat in the field. Two core histone modifications, H3K27me3 and H3K36me3, exhibited opposite patterns on the key vernalization gene VERNALIZATION1 (VRN1), correlating with its induction during cold exposure. Moreover, the H3K36me3 level remained high at VRN1 after cold exposure, which may maintain its active state. Mutations in FERTILIZATION-INDEPENDENT ENDOSPERM (TaFIE) and SET DOMAIN GROUP 8/EARLY FLOWERING IN SHORT DAYS (TaSDG8/TaEFS), components of the writer complex for H3K27me3 and H3K36me3, respectively, affected flowering time. Intriguingly, VRN1 lost its high expression after the cold exposure memory in the absence of H3K36me3. During embryo development, VRN1 was silenced with the removal of active histone modifications in both winter and spring wheat, with selective restoration of H3K27me3 in winter wheat. The mutant of Tafie-cr-87, a component of H3K27me3 "writer" complex, did not influence the silence of VRN1 during embryo development, but rather attenuated the cold exposure requirement of winter wheat. Integrating gene expression with H3K27me3 and H3K36me3 patterns identified potential regulators of flowering. This study unveils distinct roles of H3K27me3 and H3K36me3 in controlling vernalization response, maintenance, and resetting in winter wheat.

The cost of climate change: A generalized cost function approach for incorporating extreme weather exposure into public transit accessibility

Public transit offers urban populations physical accessibility to resources and opportunities. However, at the same time, transit trips often expose users to extreme environmental conditions, such as extreme heat and cold since transit journeys usually include out-of-vehicle trip segments including walking and waiting. Such exposure can be considered as environmental health costs because exposure to weather extremes can lead to adverse health outcomes. Even worse, climate change is increasing the intensity and frequency of extreme weather events. In this context, how can we make public transit accessibility measures ready for climate change? This paper attempts to answer this question by developing a generalized cost function approach combining travel time and environmental health costs into an integrated measure of dual accessibility: a measure of the travel costs of accessing a fixed number of destinations. We synthesize transport science, environmental health, remote sensing, and urban climatology to empower the proposed framework. To demonstrate the utility of the proposed method, we carry out an example study that incorporates transit passengers' extreme cold exposure into accessibility measures in the city of Winnipeg, Manitoba, Canada. Further, we perform a social equity analysis to investigate whether the increase in total integrated costs (i.e., decrease in accessibility) due to the inclusion of environmental health costs disproportionately affects socially disadvantaged population groups. The proposed method enables a more realistic and practical measurement of public transit accessibility under climate change; thereby, improving the readiness and resilience of our society and transport systems for future challenges.

Prolonged Cold Exposure Negatively Impacts Atlantic Salmon (Salmo salar) Liver Metabolism and Function.

Large-scale mortality events have occurred during the winter in Atlantic salmon sea cages in Eastern Canada and Iceland. Thus, in salmon held at 3 °C that were apparently healthy (i.e., asymptomatic) and that had 'early' and 'advanced' symptoms of 'winter syndrome'/'winter disease' (WS/WD), we measured hepatic lipid classes and fatty acid levels, and the transcript expression of 34 molecular markers of fatty liver disease (FLD; a clinical sign of WS/WD). In addition, we correlated our results with previously reported characteristics associated with this disease's progression in these same individuals. Total lipid and triacylglycerol (TAG) levels increased by ~50%, and the expression of 32 of the 34 genes was dysregulated, in fish with symptoms of FLD. TAG was positively correlated with markers of inflammation (5loxa, saa5), hepatosomatic index (HSI), and plasma aspartate aminotransferase levels, but negatively correlated with genes related to lipid metabolism (elovl5b, fabp3a, cd36c), oxidative stress (catc), and growth (igf1). Multivariate analyses clearly showed that the three groups of fish were different, and that saa5 was the largest contributor to differences. Our results provide a number of biomarkers for FLD in salmon, and very strong evidence that prolonged cold exposure can trigger FLD in this ecologically and economically important species.