The ubiquitin codes in cellular stress responses

Protein & Cell, Journal Year: 2023, Volume and Issue: 15(3), P. 157 - 190

Published: July 19, 2023

Ubiquitination/ubiquitylation, one of the most fundamental post-translational modifications, regulates almost every critical cellular process in eukaryotes. Emerging evidence has shown that essential components numerous biological processes undergo ubiquitination mammalian cells upon exposure to diverse stresses, from exogenous factors reactions, causing a dazzling variety functional consequences. Various forms ubiquitin signals generated by ubiquitylation events specific milieus, known as codes, constitute an intrinsic part myriad stress responses. These events, leading proteolytic turnover substrates or just switch functionality, initiate, regulate, supervise multiple stress-associated responses, supporting adaptation, homeostasis recovery, and survival stressed cells. In this review, we attempted summarize crucial roles response different environmental intracellular while discussing how stresses modulate system. This review also updates recent advances understanding machinery well responses discusses some important questions may warrant future investigation.

Language: Английский

---

Pathophysiology of Severe Burn Injuries: New Therapeutic Opportunities From a Systems Perspective

Journal of Burn Care & Research, Journal Year: 2024, Volume and Issue: 45(4), P. 1041 - 1050

Published: March 22, 2024

Severe burn injury elicits a profound stress response with the potential for high morbidity and mortality. If polytrauma is present, patient outcomes appear to be worse. Sex-based comparisons indicate females have worse than males. There are few effective drug therapies treat shock secondary progression. The lack of drugs appears arise from current treat-as-you-go approach rather more integrated systems approach. In this review, we present brief history burns research discuss its pathophysiology systems' perspective. severe phenotype develop rapid relentless barrage damage-associated molecular patterns, pathogen-associated neural afferent signals, which leads state hyperinflammation, immune dysfunction, coagulopathy, hypermetabolism, intense pain. We propose that if central nervous system control cardiovascular function endothelial-glycocalyx-mitochondrial coupling can restored early, these processes may minimized. therapeutic goal switch healing by reducing fluid leak maintaining tissue O2 perfusion. Currently, no systems-based exist burns. been developing small-volume therapy comprising adenosine, lidocaine, magnesium (ALM) hemorrhagic shock, traumatic brain injury, sepsis. Our early studies ALM holds some promise in supporting pulmonary functions following Future will investigate ability sex disparities, translation humans.

Language: Английский

---

Thyroid hormone remodels cortex to coordinate body-wide metabolism and exploration

Cell, Journal Year: 2024, Volume and Issue: 187(20), P. 5679 - 5697.e23

Published: Aug. 22, 2024

Animals adapt to environmental conditions by modifying the function of their internal organs, including brain. To be adaptive, alterations in behavior must coordinated with functional state organs throughout body. Here, we find that thyroid hormone-a regulator metabolism many peripheral organs-directly activates cell-type-specific transcriptional programs frontal cortex adult male mice. These are enriched for axon-guidance genes glutamatergic projection neurons, synaptic regulatory both astrocytes and pro-myelination factors oligodendrocytes, suggesting widespread plasticity cortical circuits. Indeed, whole-cell electrophysiology revealed hormone alters excitatory inhibitory transmission, an effect requires hormone-induced gene presynaptic neurons. Furthermore, action regulates innate exploratory behaviors causally promotes decision-making. Thus, acts directly on cerebral males coordinate whole-body metabolic state.

Language: Английский

---

Numerous independent gains of daily torpor and hibernation across endotherms, linked with adaptation to diverse environments

Functional Ecology, Journal Year: 2025, Volume and Issue: unknown

Published: Jan. 5, 2025

Abstract Many endotherms from diverse taxonomic groups can respond to environmental changes through torpor, that is, by greatly reducing their energy expenditure for up 24 hours (daily torpor) or longer (hibernation). We currently have a poor understanding of how torpor evolved across and its associations with physiological traits ecological factors. To fill this gap, we thoroughly examine the evolutionary patterns links 21 key variables 1338 extant endotherms. find daily hibernation are parts an continuum, there several, albeit weak, between species' characteristics. Furthermore, show early endotherm ancestors likely did not hibernate trait multiple times in independent lineages. Overall, our results suggest remarkable variation cannot solely be attributed niches, but partly arises gains various clades. Read free Plain Language Summary article on Journal blog.

Language: Английский

---

Hypothalamic hormone deficiency enables physiological anorexia in ground squirrels during hibernation

Nature Communications, Journal Year: 2024, Volume and Issue: 15(1)

Published: July 10, 2024

Abstract Mammalian hibernators survive prolonged periods of cold and resource scarcity by temporarily modulating normal physiological functions, but the mechanisms underlying these adaptations are poorly understood. The hibernation cycle thirteen-lined ground squirrels (Ictidomys tridecemlineatus) lasts for 5–7 months comprises weeks hypometabolic, hypothermic torpor interspersed with 24–48-h an active-like interbout arousal (IBA) state. We show that squirrels, who endure entire season without food, have negligible hunger during IBAs. These exhibit reversible inhibition hypothalamic feeding center, such arcuate nucleus neurons reduced sensitivity to orexigenic anorexigenic effects ghrelin leptin, respectively. However, infusion thyroid hormone IBA is sufficient rescue anorexia. Our results reveal deficiency underlies anorexia demonstrate functional flexibility center.

Language: Английский

---

Darwinian genomics and diversity in the tree of life

Proceedings of the National Academy of Sciences, Journal Year: 2022, Volume and Issue: 119(4)

Published: Jan. 18, 2022

Genomics encompasses the entire tree of life, both extinct and extant, evolutionary processes that shape this diversity. To date, genomic research has focused on humans, a small number agricultural species, established laboratory models. Fewer than 18,000 ∼2,000,000 eukaryotic species (<1%) have representative genome sequence in GenBank, only fraction these ancillary information structure, genetic variation, gene expression, epigenetic modifications, population This imbalance reflects perception human studies are paramount disease research. Yet understanding how genomes work, variation shapes phenotypes, requires broad view embraces vast diversity life. We technology to collect massive exquisitely detailed datasets about world, but expertise is siloed into distinct fields. A new approach, integrating comparative genomics with cell biology, ecology, archaeology, anthropology, conservation essential for protecting ourselves our world. Here, we describe potential scientific discovery when works close collaboration range fields as well technical, scientific, social constraints must be addressed.

Language: Английский

---

Multi-omics Investigation of Freeze Tolerance in the Amur Sleeper, an Aquatic Ectothermic Vertebrate

Molecular Biology and Evolution, Journal Year: 2023, Volume and Issue: 40(3)

Published: Feb. 18, 2023

Freeze tolerance, the ability of an organism to survive internal ice formation, is a striking survival strategy employed by some ectotherms living in cold environments. However, genetic bases this remarkable adaptation are largely unknown. The Amur sleeper (Perccottus glenii), only known freeze-tolerant fish species, can overwinter with its entire body frozen ice. Here, we sequenced chromosome-level genome and performed comparative genomic, transcriptomic, metabolomic analyses investigate strategies for surviving freezing. Evolutionary analysis suggested that diverged from closest non-cold-hardy relative about 15.07 million years ago has experienced high rate protein evolution. Transcriptomic data identified coordinated tissue-specific regulation genes metabolites involved hypometabolism, cellular stress response, cryoprotectant accumulation freezing thawing. Several show evidence accelerated sequence evolution or family size expansion were found as adaptive responses freezing-induced stresses. Specifically, changes associated cytoskeleton stability, synthesis, transmembrane transport, neuroprotective adaptations potentially key innovations aid survival. Our work provides valuable resources opportunities unveil molecular supporting freeze tolerance ectothermic vertebrates.

Language: Английский

---

Towards understanding the neural origins of hibernation

Journal of Experimental Biology, Journal Year: 2022, Volume and Issue: 225(1)

Published: Jan. 1, 2022

ABSTRACT Hibernators thrive under harsh environmental conditions instead of initiating canonical behavioral and physiological responses to promote survival. Although the changes that occur during hibernation have been comprehensively researched, role nervous system in this process remains relatively underexplored. In Review, we adopt perspective plays an active, essential facilitating supporting hibernation. Accumulating evidence strongly suggests hypothalamus enters a quiescent state which powerful drives thermoregulate, eat drink are suppressed. Similarly, cardiovascular pulmonary reflexes originating brainstem altered permit profoundly slow heart breathing rates observed torpor. The mechanisms underlying these not currently known, but several neuromodulatory systems implicated induction maintenance intersection findings with modern neuroscience approaches, such as optogenetics vivo calcium imaging, has opened exciting avenues for research.

Language: Английский

---

The intestinal microbiota and metabolic profiles of Strauchbufo raddei underwent adaptive changes during hibernation

Integrative Zoology, Journal Year: 2023, Volume and Issue: 19(4), P. 612 - 630

Published: July 10, 2023

The intestinal microbiota help regulate hibernation in vertebrates. However, it needs to be established how modulates the gut microbiome and metabolism. In present study, we used an artificial model examine responses of Strauchbufo raddei environmental changes associated with this behavior. Hibernation significantly lowered diversity altered microbial community gut. Proteobacteria, Firmicutes, Bacteroidota were major bacterial phyla intestines S. raddei. Firmicutes Proteobacteria predominated active hibernating raddei, respectively. Certain genera such as Pseudomonas, Vibrio, Ralstonia, Rhodococcus could serve biomarkers distinguishing non-hibernating was more resistant stress than Moreover, metabolomics revealed that metabolites implicated fatty acid biosynthesis highly upregulated enriched during enabled adapt low temperatures lack exogenous food are characteristic hibernation. A correlation analysis their might participate metabolic regulation study clarified modifications occur bacteria symbiotic relationship host These findings indicative adaptive metabolism amphibians under different conditions.

Language: Английский

---

Telomere dynamics during hibernation in a tropical primate

Journal of Comparative Physiology B, Journal Year: 2024, Volume and Issue: 194(2), P. 213 - 219

Published: March 11, 2024

Language: Английский

---