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One of the most exceptional adaptations to extreme drought is found in the sister group to tetrapods, the lungfishes (Dipnoi), which can aestivate inside a mucus cocoon for multiple years at reduced metabolic rates with complete cessation of ingestion and excretion. However, the function of the cocoon tissue is not fully understood. Here we developed a new more natural laboratory protocol for inducing aestivation in the West African lungfish, Protopterus annectens, and investigated the structure and function of the cocoon. We used electron microscopy and imaging of live tissue-stains to confirm that the inner and outer layers of the paper-thin cocoon are composed primarily of living cells. However, we also repeatedly observed extensive bacterial and fungal growth covering the cocoon and found no evidence of anti-microbial activity in vitro against E. coli for the cocoon tissue in this species. This classroom discovery-based research, performed during a course-based undergraduate research experience course (CURE), provides a robust laboratory protocol for investigating aestivation and calls into the question the function of this bizarre vertebrate adaptation.

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Bulinus snails surviving drought play a key role in the seasonal transmission of urogenital schistosomiasis, although our knowledge of their adaptation to dry season is still limited. We investigated the survival dynamic and infestation by the Schistosoma haematobium of Bulinus snails during the dry and rainy seasons in a single pond in an area of seasonal schistosomiasis transmission in Senegal. During the rainy season, 98 (94.23%) B. senegalensis and six (5.76%) B. umbilicatus were collected, respectively. In the dry season, B. umbilicatus outnumbered B. senegalensis, but all five (100%) B. senegalensis collected were viable and alive after the interruption of aestivation by immersion in water, while only 7 of 24 (29.16%) B. umbilicatus collected emerged from their dormant state. The rate of infestation with S. haeamatobium during the rainy season was 18.2% (19/104), while all the viable snails collected during the dry season were negative. B. senegalensis and B. umbilicatus have different seasonal dynamics with no evidence of maintaining S. haematobium infestation during the drought. Further studies including more survey sites and taking account both snails biology and ecological conditions are needed to better understand snail adaptation to seasonal changes and their ability to maintain S. haeamatobium infestation during drought.

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Hypertonic dehydration is associated with muscle wasting and synthesis of organic osmolytes. We recently showed a metabolic shift to amino acid production and urea cycle activation in coronavirus-2019 (COVID-19), consistent with the aestivation response. The aim of the present investigation was to validate the metabolic shift and development of long-term physical outcomes in the non-COVID cohort of the Biobanque Québécoise de la COVID-19 (BQC19). We included 824 patients from BQC19, where 571 patients had data of dehydration in the form of estimated osmolality (eOSM = 2Na + 2K + glucose + urea), and 284 patients had metabolome data and long-term follow-up. We correlated the degree of dehydration to mortality, invasive mechanical ventilation, acute kidney injury, and long-term symptoms. As found in the COVID cohort, higher eOSM correlated with a higher proportion of urea and glucose of total eOSM, and an enrichment of amino acids compared with other metabolites. Sex-stratified analysis indicated that women may show a weaker aestivation response. More severe dehydration was associated with mortality, invasive mechanical ventilation, and acute kidney injury during the acute illness. Importantly, more severe dehydration was associated with physical long-term symptoms but not mental long-term symptoms after adjustment for age, sex, and disease severity. Patients with water deficit in the form of increased eOSM tend to have more severe disease and experience more physical symptoms after an acute episode of care. This is associated with amino acid and urea production, indicating dehydration-induced muscle wasting.NEW & NOTEWORTHY We have previously shown that humans exhibit an aestivation-like response where dehydration leads to a metabolic shift to urea synthesis, which is associated with long-term weakness indicating muscle wasting. In the present study, we validate this response in a new cohort and present a deeper metabolomic analysis and pathway analysis. Finally, we present a sex-stratified analysis suggesting weaker aestivation in women. However, women show less dehydration, so the association warrants further study.

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BACKGROUND: Sodium-glucose cotransporter 2 inhibitors are believed to improve cardiac outcomes due to their osmotic diuretic potential. OBJECTIVES: The goal of this study was to test the hypothesis that vasopressin-driven urine concentration overrides the osmotic diuretic effect of glucosuria induced by dapagliflozin treatment. METHODS: DAPA-Shuttle1 (Hepato-renal Regulation of Water Conservation in Heart Failure Patients With SGLT-2 Inhibitor Treatment) was a single-center, double-blind, randomized, placebo-controlled trial, in which patients with chronic heart failure NYHA functional classes I/II and reduced ejection fraction were randomly assigned to receive dapagliflozin 10 mg daily or placebo (1:1) for 4 weeks. The primary endpoint was change from baseline in urine osmolyte concentration. Secondary endpoints included changes in copeptin levels and solute free water clearance. RESULTS: Thirty-three randomized, sodium-glucose cotransporter 2 inhibitor-naïve participants completed the study, 29 of whom (placebo: n = 14; dapagliflozin: n = 15) provided accurate 24-hour urine collections (mean age 59 ± 14 years; left ventricular ejection fraction 31% ± 9%). Dapagliflozin treatment led to an isolated increase in urine glucose excretion by 3.3 mmol/kg/d (95% CI: 2.51-4.04; P < 0.0001) within 48 hours (early) which persisted after 4 weeks (late; 2.7 mmol/kg/d [95% CI: 1.98-3.51]; P < 0.0001). Dapagliflozin treatment increased serum copeptin early (5.5 pmol/L [95% CI: 0.45-10.5]; P < 0.05) and late (7.8 pmol/L [95% CI: 2.77-12.81]; P < 0.01), leading to proportional reductions in free water clearance (early: -9.1 mL/kg/d [95% CI: -14 to -4.12; P < 0.001]; late: -11.0 mL/kg/d [95% CI: -15.94 to -6.07; P < 0.0001]) and elevated urine concentrations (late: 134 mmol/L [95% CI: 39.28-229.12]; P < 0.01). Therefore, urine volume did not significantly increase with dapagliflozin (mean difference early: 2.8 mL/kg/d [95% CI: -1.97 to 7.48; P = 0.25]; mean difference late: 0.9 mL/kg/d [95% CI: -3.83 to 5.62]; P = 0.70). CONCLUSIONS: Physiological-adaptive water conservation eliminated the expected osmotic diuretic potential of dapagliflozin and thereby prevented a glucose-driven increase in urine volume of approximately 10 mL/kg/d · 75 kg = 750 mL/kg/d. (Hepato-renal Regulation of Water Conservation in Heart Failure Patients With SGLT-2 Inhibitor Treatment [DAPA-Shuttle1]; NCT04080518).

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Diapause, a form of dormancy to delay or halt the reproductive development during unfavourable seasons, has evolved in many insect species. One example is aestivation, an adult-stage diapause enhancing malaria vectors' survival during the dry season (DS) and their re-establishment in the next rainy season (RS). This work develops a novel genetic approach to estimate the number or proportion of individuals undergoing diapause, as well as the breeding sizes of the two seasons, using signals from temporal allele frequency dynamics. Our modelling shows the magnitude of drift is dampened at early RS when previously aestivating individuals reappear. Aestivation severely biases the temporal effective population size ( N e $$ {N}_e $$ ), leading to overestimation of the DS breeding size by 1 / 1 - α 2 $$ 1/{\left(1-\alpha \right)}^2 $$ across 1 year, where α $$ \alpha $$ is the aestivating proportion. We find sampling breeding individuals in three consecutive seasons starting from an RS is sufficient for parameter estimation, and perform extensive simulations to verify our derivations. This method does not require sampling individuals in the dormant state, the biggest challenge in most studies. We illustrate the method by applying it to a published data set for Anopheles coluzzii mosquitoes from Thierola, Mali. Our method and the expected evolutionary implications are applicable to any species in which a fraction of the population diapauses for more than one generation, and are difficult or impossible to sample during that stage.

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Dormancy represents a fascinating adaptive strategy for organisms to survive in unforgiving environments. After a period of dormancy, organisms often exhibit exceptional resilience. This period is typically divided into hibernation and aestivation based on seasonal patterns. However, the mechanisms by which organisms adapt to their environments during dormancy, as well as the potential relationships between different states of dormancy, deserve further exploration. Here, we selected Perccottus glenii and Protopterus annectens as the primary subjects to study hibernation and aestivation, respectively. Based on histological and transcriptomic analysis of multiple organs, we discovered that dormancy involved a coordinated functional response across organs. Enrichment analyses revealed noteworthy disparities between the two dormant species in their responses to extreme temperatures. Notably, similarities in gene expression patterns pertaining to energy metabolism, neural activity, and biosynthesis were noted during hibernation, suggesting a potential correlation between hibernation and aestivation. To further explore the relationship between these two phenomena, we analyzed other dormancy-capable species using data from publicly available databases. This comparative analysis revealed that most orthologous genes involved in metabolism, cell proliferation, and neural function exhibited consistent expression patterns during dormancy, indicating that the observed similarity between hibernation and aestivation may be attributable to convergent evolution. In conclusion, this study enhances our comprehension of the dormancy phenomenon and offers new insights into the molecular mechanisms underpinning vertebrate dormancy.

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In response to seasonal droughts, the green striped burrowing frog Cyclorana alboguttata enters a reversible hypometabolic state called aestivation where heart rate and oxygen consumption can be reduced despite warm (>25C°) ambient temperatures. With a view to understanding molecular mechanisms we profiled aestivating versus control gastrocnemius muscle using mRNA sequencing. This indicated an extensive metabolic reprogramming, with nearly a quarter of the entire transcriptome (3996 of 16,960 mRNA) exhibiting a nominal >2-fold change. Consistent with a physiological adaptation to spare carbohydrate reserves, carbohydrate catabolism was systemically downregulated. A 630-fold downregulation of ENO3 encoding the enolase enzyme was most striking. The 590 frog orthologs of mRNA encoding the mitoproteome were, viewed as a population, significantly downregulated during aestivation, although not to the same extent as mRNA encoding carbohydrate catabolism. Prominent examples include members of the TCA cycle (IDH2), electron transport chain (NDUFA6), the ATP synthase complex (ATP5F1B) and ADP/ATP intracellular transport (SLC25A4). Moreover, mRNA derived from the mt genome itself (e.g. mt-ND1) were also downregulated. Most prominent among the upregulated mRNA are those encoding aspects of regulated proteolysis including the proteosome (e.g. PSME4L), peptidases (USP25), atrogins (FBXO32) and ubiquitination (VCP). Finally, we note the ∼5-fold upregulation of the mRNA EIFG3 that encodes part of the EIF4F complex. This possesses global control of protein synthesis. Given protein synthesis is repressed in aestivating frogs this indicates the skeletal musculature is poised for accelerated translation of mRNA upon emergence, supporting a strategy to rapidly restore function when the summer rains come.

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AIMS/HYPOTHESIS: Sodium-glucose co-transporter 2 (SGLT2) inhibitors (SGLT2i) are antihyperglycaemic drugs that protect the kidneys of individuals with type 2 diabetes mellitus. However, the underlying mechanisms mediating the renal benefits of SGLT2i are not fully understood. Considering the fuel switches that occur during therapeutic SGLT2 inhibition, we hypothesised that SGLT2i induce fasting-like and aestivation-like metabolic patterns, both of which contribute to the regulation of metabolic reprogramming in diabetic kidney disease (DKD). METHODS: Untargeted and targeted metabolomics assays were performed on plasma samples from participants with type 2 diabetes and kidney disease (n=35, 11 women) receiving canagliflozin (CANA) 100 mg/day at baseline and 12 week follow-up. Next, a systematic snapshot of the effect of CANA on key metabolites and pathways in the kidney was obtained using db/db mice. Moreover, the effects of glycine supplementation in db/db mice and human proximal tubular epithelial cells (human kidney-2 [HK-2]) cells were studied. RESULTS: Treatment of DKD patients with CANA for 12 weeks significantly reduced HbA1c from a median (interquartile range 25-75%) of 49.0 (44.0-57.0) mmol/mol (7.9%, [7.10-9.20%]) to 42.2 (39.7-47.7) mmol/mol (6.8%, [6.40-7.70%]), and reduced urinary albumin/creatinine ratio from 67.8 (45.9-159.0) mg/mmol to 47.0 (26.0-93.6) mg/mmol. The untargeted metabolomics assay showed downregulated glycolysis and upregulated fatty acid oxidation. The targeted metabolomics assay revealed significant upregulation of glycine. The kidneys of db/db mice undergo significant metabolic reprogramming, with changes in sugar, lipid and amino acid metabolism; CANA regulated the metabolic reprogramming in the kidneys of db/db mice. In particular, the pathways for glycine, serine and threonine metabolism, as well as the metabolite of glycine, were significantly upregulated in CANA-treated kidneys. Glycine supplementation ameliorated renal lesions in db/db mice by inhibiting food intake, improving insulin sensitivity and reducing blood glucose levels. Glycine supplementation improved apoptosis of human proximal tubule cells via the AMP-activated protein kinase (AMPK)/mammalian target of rapamycin (mTOR) pathway. CONCLUSIONS/INTERPRETATION: In conclusion, our study shows that CANA ameliorates DKD by inducing fasting-like and aestivation-like metabolic patterns. Furthermore, DKD was ameliorated by glycine supplementation, and the beneficial effects of glycine were probably due to the activation of the AMPK/mTOR pathway.

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Different populations of hosts and parasites experience distinct seasonality in environmental factors, depending on local-scale biotic and abiotic factors. This can lead to highly heterogeneous disease outcomes across host ranges. Variable seasonality characterizes urogenital schistosomiasis, a neglected tropical disease caused by parasitic trematodes (Schistosoma haematobium). Their intermediate hosts are aquatic Bulinus snails that are highly adapted to extreme rainfall seasonality, undergoing prolonged dormancy yearly. While Bulinus snails have a remarkable capacity for rebounding following dormancy, we investigated the extent to which parasite survival within snails is diminished. We conducted an investigation of seasonal snail schistosome dynamics in 109 ponds of variable ephemerality in Tanzania from August 2021 to July 2022. First, we found that ponds have two synchronized peaks of schistosome infection prevalence and observed cercariae, though of lower magnitude in the fully desiccating than non-desiccating ponds. Second, we evaluated total yearly schistosome prevalence across an ephemerality gradient, finding ponds with intermediate ephemerality to have the highest infection rates. We also investigated dynamics of non-schistosome trematodes, which lacked synonymity with schistosome patterns. We found peak schistosome transmission risk at intermediate pond ephemerality, thus the impacts of anticipated increases in landscape desiccation could result in increases or decreases in transmission risk with global change.

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BACKGROUND: Semi-natural habitats are generally considered to be beneficial to natural enemies of crop pests and pollinators. However, they could also be used by pests, such as the Cabbage Stem Flea Beetle (CSFB), Psylliodes chrysocephala, a major pest of winter oilseed rape, Brassica napus. Adults emerge from pupation in late spring and move to aestivation habitats. Published reports identify forest edges as the major shelter used, but flower strips may also constitute an alternative habitat. This study aimed to: (i) determine the role of perennial flower strips in CSFB aestivation in comparison with woodland edges; (ii) determine the influence of landscape composition on the abundance of aestivating CSFB and (iii) identify the characteristics of the local habitat associated with a high abundance of aestivating CSFB. RESULTS: CSFB emergence from aestivation was monitored with emergence traps from mid-August to mid-October 2021, at 14 sites in France. We found that CSFB preferred woodland edges and did not aestivate in flower strips. We found a negative effect of percentage woodland cover only for the smallest scale studied (250 m radius). We also found positive effects of the percentage of litter and mean tree circumference on the number of aestivating CSFB in woodland edges. CONCLUSION: The aestivation of CSFB is supported by woodland edges, but not by flower strips. This implies that the presence of flower strips near oilseed rape fields does not exacerbate the problems due to this pest. However, the crops in the vicinity of woodlands could be colonized earlier by this pest than more distant fields. © 2023 Society of Chemical Industry.

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Aestivation is considered to be one of the "purest" hypometabolic states in nature, as it involves aerobic dormancy that can be induced and sustained without complex factors. Animals that undergo aestivation to protect themselves from environmental stressors such as high temperatures, droughts, and food shortages. However, this shift in body metabolism presents new challenges for survival, including oxidative stress upon awakening from aestivation, accumulation of toxic metabolites, changes in energy sources, adjustments to immune status, muscle atrophy due to prolonged immobility, and degeneration of internal organs due to prolonged food deprivation. In this review, we summarize the physiological and metabolic strategies, key regulatory factors, and networks utilized by aestivating animals to address the aforementioned components of aestivation. Furthermore, we present a comprehensive overview of the advancements made in aestivation research across major species, including amphibians, fish, reptiles, annelids, mollusks, and echinoderms, categorized according to their respective evolutionary positions. This approach offers a distinct perspective for comparative analysis, facilitating an understanding of the shared traits and unique features of aestivation across different groups of organisms.

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Background/Aims: Cells adapt to chronic extracellular hypotonicity by altering metabolism. Corresponding effects of sustained hypotonic exposure at the whole-person level remain to be confirmed and characterized in clinical and population-based studies. This analysis aimed to 1) describe changes in urine and serum metabolomic profiles associated with four weeks of sustained > +1 L/d drinking water in healthy, normal weight, young men, 2) identify metabolic pathways potentially impacted by chronic hypotonicity, and 3) explore if effects of chronic hypotonicity differ by type of specimen and/or acute hydration condition. Materials: Untargeted metabolomic assays were completed for specimen stored from Week 1 and Week 6 of the Adapt Study for four men (20-25 years) who changed hydration classification during that period. Each week, first-morning urine was collected after overnight food and water restriction, and urine (t+60 min) and serum (t+90 min) were collected after a 750 mL bolus of drinking water. Metaboanalyst 5.0 was used to compare metabolomic profiles. Results: In association with four weeks of > + 1 L/d drinking water, urine osmolality decreased below 800 mOsm/kg H2O and saliva osmolality decreased below 100 mOsm/kg H2O. Between Week 1 and Week 6, 325 of 562 metabolic features in serum changed by 2-fold or more relative to creatinine. Based on hypergeometric test p-value <0.05 or Kyoto Encyclopedia of Genes and Genomes (KEGG) pathway impact factor >0.2, the sustained > + 1 L/d of drinking water was associated with concurrent changes in carbohydrate, protein, lipid, and micronutrient metabolism, a metabolomic pattern of carbohydrate oxidation via the tricarboxylic acid (TCA) cycle, instead of glycolysis to lactate, and a reduction of chronic disease risk factors in Week 6. Similar metabolic pathways appeared potentially impacted in urine, but the directions of impact differed by specimen type. Conclusion: In healthy, normal weight, young men with initial total water intake below 2 L/d, sustained > + 1 L/d drinking water was associated with profound changes in serum and urine metabolomic profile, which suggested normalization of an aestivation-like metabolic pattern and a switch away from a Warburg-like pattern. Further research is warranted to pursue whole-body effects of chronic hypotonicity that reflect cell-level effects and potential beneficial effects of drinking water on chronic disease risk.

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Different populations of hosts and parasites experience distinct seasonality in environmental factors, depending on local-scale biotic and abiotic factors. This can lead to highly heterogenous disease outcomes across host ranges. Variable seasonality characterizes urogenital schistosomiasis, a neglected tropical disease caused by parasitic trematodes (Schistosoma haematobium). Their intermediate hosts are aquatic Bulinus snails that are highly adapted to extreme rainfall seasonality, undergoing dormancy for up to seven months yearly. While Bulinus snails have a remarkable capacity for rebounding following dormancy, parasite survival within snails is greatly diminished. We conducted a year-round investigation of seasonal snail-schistosome dynamics in 109 ponds of variable ephemerality in Tanzania. First, we found that ponds have two synchronized peaks of schistosome infection prevalence and cercariae release, though of lower magnitude in the fully desiccating ponds than non-desiccating ponds. Second, we evaluated total yearly prevalence across a gradient of an ephemerality, finding ponds with intermediate ephemerality to have the highest infection rates. We also investigated dynamics of non-schistosome trematodes, which lacked synonymity with schistosome patterns. We found peak schistosome transmission risk at intermediate pond ephemerality, thus the impacts of anticipated increases in landscape desiccation could result in increases or decreases in transmission risk with global change.

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Environmental perturbations evoke down-regulation of metabolism in some multicellular organisms, leading to dormancy, or torpor. Colonies of the urochordate Botrylloides leachii enter torpor in response to changes in seawater temperature and may survive for months as small vasculature remnants that lack feeding and reproductive organs but possess torpor-specific microbiota. Upon returning to milder conditions, the colonies rapidly restore their original morphology, cytology and functionality while harboring re-occurring microbiota, a phenomenon that has not been described in detail to date. Here we investigated the stability of B. leachii microbiome and its functionality in active and dormant colonies, using microscopy, qPCR, in situ hybridization, genomics and transcriptomics. A novel lineage of Endozoicomonas, proposed here as Candidatus Endozoicomonas endoleachii, was dominant in torpor animals (53-79% read abundance), and potentially occupied specific hemocytes found only in torpid animals. Functional analysis of the metagenome-assembled genome and genome-targeted transcriptomics revealed that Endozoicomonas can use various cellular substrates, like amino acids and sugars, potentially producing biotin and thiamine, but also expressing various features involved in autocatalytic symbiosis. Our study suggests that the microbiome can be linked to the metabolic and physiological states of the host, B. leachii, introducing a model organism for the study of symbioses during drastic physiological changes, such as torpor.

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Treatment with a sodium glucose cotransporter 2 (SGLT2) inhibitor in patients with chronic kidney disease reduces the renal risk independent of changes in blood glucose concentrations and blood pressure. However, the precise mechanism responsible for this SGLT2 inhibitor-induced renoprotective effect is unclear. We have previously shown that SGLT2 inhibitors induce antihypertensive effects with decreased sympathetic nerve activity, which is associated with transient natriuresis. Furthermore, treatment with an SGLT2 inhibitor improves renal ischemia by producing vascular endothelial growth factor-a in the renal tubules. Other studies have suggested that ketone body production, changes in glomerular hemodynamics, and intrarenal metabolic changes and a reduction in oxidative stress due to decreased tubulointerstitial glucose levels may also be involved in the renoprotective effects of SGLT2 inhibitors. In this review, we summarize the mechanism responsible for the SGLT2 inhibitor-induced renoprotective effects, including our recent hypothesis regarding an "aestivation-like response," which is a biological defense response to starvation.

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African dipnoi (Protopterus sp.) are obligate air-breathing fish that, during dry season, may experience a period of dormancy named aestivation. Aestivation is characterized by complete reliance on pulmonary breathing, general decrease of metabolism and down-regulation of respiratory and cardiovascular functions. To date, little is known about morpho-functional rearrangements induced by aestivation in the skin of African lungfishes. Our study aims to identify, in the skin of P. dolloi, structural modifications and stress-induced molecules in response to short-term (6 days) and long-term (40 days) aestivation. Light microscopy showed that short-term aestivation induces major reorganization, with narrowing of epidermal layers and decrease of mucous cells; prolonged aestivation is characterized by regenerative processes and re-thickening of epidermal layers. Immunofluorescence reveals that aestivation correlates with an increased oxidative stress and changes of Heat Shock Proteins expression, suggesting a protective role for these chaperons. Our findings revealed that lungfish skin undergoes remarkable morphological and biochemical readjustments in response to stressful conditions associated with aestivation.

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Aestivation is a special ability possessed by some animals to cope with hot and dry environments utilizing dormancy. At a macroscopic level, dormant animals stop moving and eating. At the microscopic level, the expression of a large number of genes in these animals is strictly controlled. However, little is known about what changes occur during aestivation, especially in fish. In this study, we used transcriptome analysis to examine what changes occur in the gills and lungs of the African lungfish (Protopterus annectens) during the maintenance phase of aestivation and speculated on their causes. We found that aestivating transcriptomes were highly similar between gills and lungs. We also found that some genes showed differential expression or alternative splicing, which may be associated with different organs. In addition, differential expression analysis revealed that the lungs maintained significantly higher bioactivity during aestivation, which suggests that the main respiratory organ in aestivating lungfish can transform. Our study provides a reference point for studying the relationship between aestivation and hibernation and further increases understanding of aestivation.

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The constant increase in temperatures under global warming has led to a prolonged aestivation period for Apostichopus japonicus, resulting in considerable losses in production and economic benefits. However, the specific mechanism of aestivation has not been fully elucidated. In this study, we first tried to illustrate the biological mechanisms of aestivation from the perspective of the gut microbiota and metabolites. Significant differences were found in the gut microbiota of aestivating adult A. japonicus (AAJSD group) compared with nonaestivating adult A. japonicus (AAJRT group) and young A. japonicus (YAJRT and YAJSD groups) based on 16S rRNA gene high-throughput sequencing analysis. The abundances of Desulfobacterota, Myxococcota, Bdellovibrionota, and Firmicutes (4 phyla) in the AAJSD group significantly increased. Moreover, the levels of Pseudoalteromonas, Fusibacter, Labilibacter, Litorilituus, Flammeovirga, Polaribacter, Ferrimonas, PB19, and Blfdi19 genera were significantly higher in the AAJSD group than in the other three groups. Further analysis of the LDA effect size showed that species with significant variation in abundance in the AAJSD group, including the phylum Firmicutes and the genera Litorilituus, Fusibacter, and Abilibacter, might be important biomarkers for aestivating adult A. japonicus. In addition, the results of metabolomics analysis showed that there were three distinct metabolic pathways, namely biosynthesis of secondary metabolites, tryptophan metabolism, and sesquiterpenoid and triterpenoid biosynthesis in the AAJSD group compared with the other three groups. Notably, 5-hydroxytryptophan was significantly upregulated in the AAJSD group in the tryptophan metabolism pathway. Moreover, the genera Labilibacter, Litorilituus, Ferrimonas, Flammeovirga, Blfdi19, Fusibacter, Pseudoalteromonas, and PB19 with high abundance in the gut of aestivating adult A. japonicus were positively correlated with the metabolite 5-HTP. These findings suggest that there may be potential biological associations among the gut microbiota, metabolites, and aestivation in A. japonicus. This work may provide a new perspective for further understanding the aestivation mechanism of A. japonicus.

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The unfolded protein response (UPR) is a wide-ranging cellular response to accumulation of malfolded proteins in the endoplasmic reticulum (ER) and acts as a quality control mechanism to halt protein processing and repair/destroy malfolded proteins under stress conditions of many kinds. Among vertebrate species, amphibians experience the greatest challenges in maintaining water and osmotic balance, the high permeability of their skin making them very susceptible to dehydration and challenging their ability to maintain cellular homeostasis. The present study evaluates the involvement of the UPR in dealing with dehydration-mediated disruption of protein processing in the tissues of African clawed frogs, Xenopus laevis. This primarily aquatic frog must deal with seasonal drought conditions in its native southern Africa environment. Key markers of cellular stress that impact protein processing were identified in six tissues of frogs that had lost 28% of total body water, as compared with fully hydrated controls. This included upregulation of glucose-regulated proteins (GRPs) that are resident chaperones in the ER, particularly 2-ninefold increases in GRP58, GRP75, and/or GRP94 in the lung and skin. Activating transcription factors (ATF3, ATF4, ATF6) that mediate UPR responses also responded to dehydration stress, particularly in skeletal muscle where both ATF3 and ATF4 rose strongly in the nucleus. Other protein markers of the UPR including GADD34, GADD153, EDEM, and XBP-1 also showed selective upregulation in frog tissues in response to dehydration and nuclear levels of the transcription factors XBP-1 and P-CREB rose indicating up-regulation of genes under their control.

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How malaria mosquitoes persist during the dry season in the Sahel and rapidly rebound at the onset of rains is unclear. Recently, Faiman and colleagues demonstrated that aestivation, a summer dormancy mechanism, is a major persistence strategy of Anopheles mosquitoes, which could be targeted by vector control.

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