Project description:We made rat models of mild, moderate and severe hypothermia, and performed body temperature-dependent microRNA expression analysis in illiopsoas muscle.
Project description:Diagnosis of fatal hypothermia is considered to be difficult in forensic practice. In this study, in order to identify novel molecular markers of fatal hypothermia, we made rat models of mild, moderate and severe hypothermia, and performed body temperature-dependent gene expression analysis in illiopsoas muscle using next-generation sequencing.
Project description:Mammalian body temperature oscillates with the time of the day and is altered in diverse pathological conditions. We recently identified a body temperature-sensitive thermometer-like kinase, which alters SR protein phosphorylation and thereby globally controls alternative splicing (AS). AS can generate unproductive variants which are recognized and degraded by diverse mRNA decay pathways – including nonsense-mediated decay (NMD). Here we show extensive coupling of body temperature-controlled AS to mRNA decay, leading to global control of temperature-dependent gene expression (GE). Temperature-controlled, decay-inducing splicing events are evolutionarily conserved and pervasively found within RNA-binding proteins, including most SR proteins. AS-coupled poison exon inclusion is essential for rhythmic GE of SR proteins and has a global role in establishing temperature-dependent rhythmic GE profiles, both, in mammals under circadian body temperature cycles and in plants in response to ambient temperature changes. Together, these data identify body temperature-driven AS coupled mRNA decay as an evolutionary ancient, core clock-independent mechanism to generate rhythmic GE.
Project description:Homoeothermic organisms maintain their core body temperature in a narrow, tightly controlled range. Whether and how subtle circadian oscillations or disease-associated changes in core body temperature are sensed and integrated in gene expression programs remains elusive. Furthermore, a thermo-sensor capable of sensing the small temperature differentials leading to temperature-dependent sex determination (TSD) in poikilothermic reptiles has not been identified. Here we show that the activity of CDC-like kinases (CLKs) is highly responsive to physiological temperature changes, which is conferred by structural rearrangements within the kinase activation segment. Lower body temperature activates CLKs resulting in strongly increased phosphorylation of SR-proteins in vitro and in vivo. This globally controls temperature-dependent alternative splicing and gene expression, with wide implications in circadian, tissue-specific and disease-associated settings. This temperature sensor is conserved across evolution and adapted to growth temperatures of diverse poikilotherms. The dynamic temperature range of reptilian CLK homologs suggests a role in TSD.
Project description:Anti-viral innate immunity represents the first line of defense against invading viruses and is key to control viral infections, including the pandemic SARS-CoV-2. Body temperature is an omnipresent variable but was so far neglected when addressing host defense mechanisms and susceptibility to SARS-CoV-2 infection. Here we show that increasing temperature in a 1.5°C window, between 36.5°C and 38°C, strongly increases anti-viral immunity. We show that alternative splicing coupled to nonsense-mediated decay decreases STAT2 expression in colder conditions and suggest that increased STAT2 expression at elevated temperature induces the expression of diverse anti-viral genes. This cascade is activated in a remarkably narrow temperature range below febrile temperature, which reflects individual, circadian and age-dependent body temperature variation. Accordingly, decreased body temperature with ageing correlates with reduced expression of anti-viral genes in older individuals. Using cell culture and in vivo models, we show that higher body temperature indeed reduces SARS-CoV-2 replication, which likely impacts on the different vulnerability of children versus seniors towards severe SARS-CoV-2 infection. Altogether, our data reveal a molecular mechanism, from temperature sensing and pre-mRNA processing to an in vivo phenotype connecting body temperature variation with SARS-CoV-2 replication, thus providing a new paradigm for the regulation of anti-viral innate immunity.
Project description:To further understand the gene expression characteristics of Pseudomonas aeruginosa PAO1, we have applied whole genome microarray expression profiling as a discovery platform to specify the temperature dependent expression of PAO1 genome at soil and human body temperature. We selected 28°C as temperature representative of the soil niche and 37°C for human body. The results from the temperature dependent transcriptome analysis are consistent to our previous published data that the phzM, ptsP and lasI genes expression is upregulated at 37°C [11]. The comparison analysis of the M18 genome expressional profiles at 28°C and 37°C indicated a total of 596 genes expressed in a temperature dependent manner over two fold.
Project description:Intervention1: Normothermia Group: Normothermia will be maintained throughout CRS and warming devices will not be stopped before starting HIPEC.
Control Intervention1: Passive Hypothermia Before HIPEC: As per our standard anesthesia protocol, warming devices will be stopped 1 hour before the HIPEC phase to maintain temperature between 34.5-35.0 degree C.
Primary outcome(s): Proportion of patients who have achieved normal body temperature of at least 35 degree C post HIPECTimepoint: Immediately (0 hour) after shifting the patients to ICU or postanaesthesia care unit.
Study Design: Randomized, Parallel Group Trial Method of generating randomization sequence:Computer generated randomization Method of allocation concealment:On-site computer system Blinding and masking:Open Label
Project description:To further understand the gene expression characteristics of originating biocontrol strain Pseudomonas aeruginosa M18, we have applied whole genome microarray expression profiling as a discovery platform to to specify the temperature dependent expression of M18 genome at rhizosphere and human body temperature. We selected 28°C as temperature representative of the rhizosphere niches and 37°C for human body. The results from the temperature dependent transcriptome analysis are consistent to our previous published data that the phzM, ptsP and lasI genes expression is upregulated at 37°C. The comparison analysis of the M18 genome expressional profiles at 28°C and 37°C indicated a total of 605 gene expressed in a temperature dependent manner over about two fold at 28°C compared that at 37°C, covering 10.6% genes in M18 whole genome.
Project description:Stenotrophomonas maltophilia is an emerging multidrug resistance opportunistic pathogen affecting immunocompromised and hospitalized patients. S. maltophilia is an environmental bacterium which adapts to human body and causing infection. S. rhizophilia, a non-pathogenic and phylogenetic neighbour of S. maltophilia is unable to grow at human body temperature. Thus, to understand molecular mechanism underlying the adaptation of S. maltophilia at human body temperature, we performed the comparative transcriptome analysis of S.maltophilia at 28 °C (representative for the environmental niches) and 37 °C (representative for human body) by using RNA-Seq. The major temperature-induced genes include genes for Type IV secretion system, aerotaxis, and cation diffusion facilitator family transporter suggesting its potential role in the adaptation and virulence of S. maltophilia. The downregulated genes at 37 °C includes the genes for the cell motility, energy generation and metabolism, lipid metabolism, translation, amino acid metabolism and transport, replication and repair, inorganic ion and transport metabolism lipid metabolism, coenzyme metabolism.