Introgression drives adaptation to the plateau environment in a subterranean rodent.

BACKGROUND: Introgression has repeatedly been shown to play an important role in the adaptation of species to extreme environments, yet how introgression enables rodents with specialized subterranean lifestyle to acclimatize to high altitudes is still unclear. Myospalacinae is a group of subterranean rodents, among which the high-altitude plateau zokors (Eospalax baileyi) and the low-altitude Gansu zokors (E. cansus) are sympatrically distributed in the grassland ecosystems of the Qinghai-Tibet Plateau (QTP). Together, they provide a model for the study of the role of introgression in the adaptation of low-altitude subterranean rodents to high altitudes. RESULTS: Applying low-coverage whole-genome resequencing and population genetics analyses, we identified evidence of adaptive introgression from plateau zokors into Gansu zokors, which likely facilitated the adaptation of the latter to the high-altitude environment of the QTP. We identified positively selected genes with functions related to energy metabolism, cardiovascular system development, calcium ion transport, and response to hypoxia which likely made critical contributions to adaptation to the plateau environment in both plateau zokors and high-altitude populations of Gansu zokors. CONCLUSIONS: Introgression of genes associated with hypoxia adaptation from plateau zokors may have played a role in the adaptation of Gansu zokors to the plateau environment. Our study provides new insights into the understanding of adaptive evolution of species on the QTP and the importance of introgression in the adaptation of species to high-altitude environments.

Microbial Primer: Phase variation - survival and adaptability by generation of a diverse population.

Phase variation is defined as the rapid and reversible switching of gene expression, and typically occurs in genes encoding surface features in small genome bacterial pathogens. Phase variation has evolved to provide an extra survival mechanism in bacteria that lack multiple 'sense-and-respond' gene regulation systems. Many bacterial pathogens also encode DNA methyltransferases that are phase-variable, controlling systems called 'phasevarions' (phase-variable regulons). This primer will summarize the current understanding of phase variation, describing the role of major phase-variable factors, and phasevarions, in bacterial pathobiology.

Adaptation of feeding behaviors on two Brassica species by colonizing and noncolonizing Bemisia tabaci (Hemiptera: Aleyrodidae) NW whiteflies.

Bemisia tabaci New World (NW) (Gennadius) (Hemiptera: Aleyrodidae), a whitefly in the B. tabaci species complex, is polyphagous on many plant species. Yet, it has been displaced, albeit not entirely, by other whitefly species. Potential causes could include issues with adaptation, feeding, and the colonization of new-hosts; however, insights that would help clarify these possibilities are lacking. Here, we sought to address these gaps by performing electropenetrography (EPG) recordings of NW whiteflies, designated "Napus" and "Rapa," reared on 2 colony hosts, Brassica napus and B. rapa, respectively. Analysis of 17 probing and pathway (pw) phase-related EPG variables revealed that the whiteflies exhibited unique probing behaviors on their respective colony hosts, with some deterrence being encountered on B. rapa. Upon switching to B. rapa and B. napus, the probing patterns of Napus and Rapa whiteflies, respectively, adapted quickly to these new-hosts to resemble that of whiteflies feeding on their colony hosts. Results for 3 of the EPG variables suggested that B. rapa's deterrence against Napus whitefly was significant prior to the phloem phase. This also suggested that adaptation by Rapa whitefly improved its pw probing on B. rapa. Based on analysis of 24 phloem phase-related EPG variables, Napus and Rapa whiteflies performed equally well once they entered phloem phase and exhibited comparable phloem acceptability on both the colony- and new-hosts. These findings demonstrate that NW whiteflies reared on a colony host are highly adaptable to feeding on a new host despite encountering some deterrence during the nonphloem phases in B. rapa plant.

Fibre-specific mitochondrial protein abundance is linked to resting and post-training mitochondrial content in the muscle of men.

Analyses of mitochondrial adaptations in human skeletal muscle have mostly used whole-muscle samples, where results may be confounded by the presence of a mixture of type I and II muscle fibres. Using our adapted mass spectrometry-based proteomics workflow, we provide insights into fibre-specific mitochondrial differences in the human skeletal muscle of men before and after training. Our findings challenge previous conclusions regarding the extent of fibre-type-specific remodelling of the mitochondrial proteome and suggest that most baseline differences in mitochondrial protein abundances between fibre types reported by us, and others, might be due to differences in total mitochondrial content or a consequence of adaptations to habitual physical activity (or inactivity). Most training-induced changes in different mitochondrial functional groups, in both fibre types, were no longer significant in our study when normalised to changes in markers of mitochondrial content.

Spatially heterogeneous selection and inter-varietal differentiation maintain population structure and local adaptation in a widespread conifer.

BACKGROUND: Douglas-fir (Pseudotsuga menziesii [Mirb.] Franco) plays a critical role in the ecology and economy of Western North America. This conifer species comprises two distinct varieties: the coastal variety (var. menziesii) along the Pacific coast, and the interior variety (var. glauca) spanning the Rocky Mountains into Mexico, with instances of inter-varietal hybridization in Washington and British Columbia. Recent investigations have focused on assessing environmental pressures shaping Douglas-fir's genomic variation for a better understanding of its evolutionary and adaptive responses. Here, we characterize range-wide population structure, estimate inter-varietal hybridization levels, identify candidate loci for climate adaptation, and forecast shifts in species and variety distribution under future climates. RESULTS: Using a custom SNP-array, we genotyped 540 trees revealing four distinct clusters with asymmetric admixture patterns in the hybridization zone. Higher genetic diversity observed in coastal and hybrid populations contrasts with lower diversity in inland populations of the southern Rockies and Mexico, exhibiting a significant isolation by distance pattern, with less marked but still significant isolation by environment. For both varieties, we identified candidate loci associated with local adaptation, with hundreds of genes linked to processes such as stimulus response, reactions to chemical compounds, and metabolic functions. Ecological niche modeling revealed contrasting potential distribution shifts among the varieties in the coming decades, with interior populations projected to lose habitat and become more vulnerable, while coastal populations are expected to gain suitable areas. CONCLUSIONS: Overall, our findings provide crucial insights into the population structure and adaptive potential of Douglas-fir, with the coastal variety being the most likely to preserve its evolutionary path throughout the present century, which carry implications for the conservation and management of this species across their range.

Sex-Specific Differences in Cardiovascular Adaptations and Risks in Elite Athletes: Bridging the Gap in Sports Cardiology.

BACKGROUND: The growing participation of women in competitive sports necessitates a comprehensive understanding of sex-specific cardiovascular adaptations and risks. Historically, research has predominantly focused on male athletes, leaving a gap in knowledge about the unique cardiovascular dynamics of female peers. HYPOTHESIS: we hypothesized that female athletes exhibit distinct cardiovascular adaptations and face different risks, influenced by physiological, hormonal, and structural differences. METHODS: A systematic review of the literature was conducted, analyzing studies on cardiovascular responses and adaptations in athletes. Data were extracted on hemodynamic changes, autonomic and neural reflex regulation, cardiac remodeling, and arrhythmias. Comparative analyses were performed to identify sex-specific patterns and discrepancies in cardiovascular health outcomes. RESULTS: We revealed considerable sex differences in cardiovascular adaptations to athletic training. Female athletes generally have longer QT intervals, greater sinoatrial node automaticity, and enhanced atrioventricular node function compared to males. They also exhibit lower sympathetic activity, lower maximal stroke volumes, and a tendency toward eccentric cardiac remodeling. Conversely, male athletes are more prone to concentric hypertrophy and higher incidences of bradyarrhythmia and accessory pathway arrhythmias. Female athletes are more likely to experience symptomatic atrial fibrillation and face higher procedural complications during catheter ablation. CONCLUSIONS: Our findings underscore the necessity for sex-specific approaches in sports cardiology. Recognizing and addressing these differences could enhance performance and reduce adverse cardiac events in athletes. Future research should focus on developing tailored screening, prevention, and treatment strategies to bridge the knowledge gap and promote cardiovascular health in both male and female athletes.

A Comparative Analysis of High-Intensity Technique-Specific Intervals and Short Sprint Interval Training in Taekwondo Athletes: Effects on Cardiorespiratory Fitness and Anaerobic Power.

Technique-specific high-intensity interval training (HIITTS) has been proven to be an effective method to enhance the sport-specific bio-motor abilities of taekwondo athletes. However, studies regarding its effects on comprehensive measures of cardiorespiratory fitness are limited. Furthermore, there is a lack of clarity regarding the extent of individual adaptations to this method compared to HIIT in the form of repeated sprints (HIITRS). This study compared the individual adaptations to HIITRS and HIITTS on cardiorespiratory fitness and anaerobic power in trained taekwondo athletes (age = 19.8 ± 1.3 years; body mass = 75.4 ± 9.1 kg; height = 1.73 ± 0.0 .m). All participants completed three sessions per week of a 60-minute regular taekwondo training. Following the 60-minute training, participants completed 3 sets of 10 × 4 s all-out HIITRS or same sets of repeated kicks with both legs (HIITTS) over a 6-week training period. In both groups, rest intervals were set at 15 seconds between efforts and one minute between sets. Before and after the training period, participants underwent a series of lab- and field-based tests to evaluate cardiorespiratory fitness and bio-motor abilities. Both interventions resulted in significant improvements in maximum oxygen uptake (V̇O2max), O2 pulse (V̇O2/HR), first ventilatory threshold (VT1), second ventilatory threshold (VT2), cardiac output (Q̇max), stroke volume (SV), peak power output (PPO), average power output (APO), squat jump (SJ), and countermovement jump (CMJ). However, linear speed (20-m speed time) and taekwondo-specific agility test (TSAT) only responded to HIITRS. HIITRS resulted in greater changes in V̇O2max, V̇O2/HR, VT2, and Q̇max, and higher percentage of responders in measured parameters than HIITTS. In addition, HIITRS elicited lower inter-individual variability (CV) in percent changes from pre- to post-training in all measured variables. These results suggest that incorporating 3 sessions per week of HIITRS into regular taekwondo training results in significantly greater and more homogenized adaptations in cardiorespiratory fitness and bio-motor abilities than HIITTS among trained taekwondo athletes.

Chronic binge alcohol mediated hepatic metabolic adaptations in SIV-infected female rhesus macaques.

AIMS: As the interactions of alcohol and HIV/SIV infection and their impact on liver metabolic homeostasis remain to be fully elucidated, this study aimed to determine alcohol-mediated hepatic adaptations of metabolic pathways in SIV/ART-treated female rhesus macaques fed a nutritionally balanced diet. METHODS: Macaques were administered chronic binge alcohol (CBA; 13-14 g ethanol/kg/week for 14.5 months; n = 7) or vehicle (VEH; n = 8) for 14.5 months. Livers were excised following an overnight fast. Gene and protein expression, enzymatic activity, and lipid content were determined using frozen tissue and histological staining was performed using paraffin-embedded tissue. RESULTS: CBA/SIV macaques showed increased hepatic protein expression of electron transport Complex III and increased gene expression of glycolytic (phosphofructokinase and aldolase) and gluconeogenic (pyruvate carboxylase) enzymes and of genes involved in lipid turnover homeostasis (perilipin 1, peroxisome proliferator-activated receptor gamma, carbohydrate responsive binding protein, and acetyl-CoA carboxylase B) as compared to that of livers from the VEH/SIV group. Plasma triglyceride concentration had a significant positive association with liver triglyceride content in the CBA/SIV group. CONCLUSIONS: These results reflect CBA-associated alterations in expression of proteins and genes involved in glucose and lipid metabolism homeostasis without significant evidence of steatosis or dysglycemia. Whether these changes predispose to greater liver pathology upon consumption of a high fat/high sugar diet that is more aligned with dietary intake of PWH and/or exposure to additional environmental factors warrants further investigation.

Mechanical properties of the patellar tendon in weightlifting athletes - the utility of myotonometry. Adaptations of patellar tendon to mechanical loading.

Purpose: Tendons adapt to loads applied to them, by changing their own mechanical properties. The purpose of the study was to examine the influence of practicing sport in the form of weightlifting/strength training by individuals of various age groups upon the mechanical properties of the patellar tendon. Methods: 200 people participated in the study. Group 1 (n = 109) comprised individuals training strength sports as amateurs, group 2 (n = 91) consisted of people who were not physically active. The patellar tendon was examined in various positions of the knee joint: 0, 30, 60, 90, 120° respectively. The following mechanical parameters were measured with the use of a device for myoto-nometric measurements, MyotonPRO: frequency [Hz], stiffness [N/m], decrement [log], relaxation time [ms] and creep [De]. The results were compared as regards physical activity, training history, BMI value, and gender. Results: Stiffness and tone increased while elasticity decreased with patellar tendon stretching degree. In the group of individuals in training, greater stiffness and tone and lower elasticity were noted. Moreover, stiffness and tone appeared to be higher in elderly people and individuals with longer training experience. Conclusions: Mechanical loads connected with strength training result in development of adaptive changes in the patellar tendon, in the form of higher stiffness and tone, as well as lower elasticity. The MyotonPRO device is useful for quantitative assessment of the mechanical properties of patellar tendon.

The adaptation of lichen symbiosis to desert saline-alkali stress depends more on their symbiotic algae.

Soil salinization is a major environmental threat to the entire terrestrial ecosystem. Lichens arose from the symbiosis of fungi and algae or cyanobacteria. They have a high tolerance to various extreme environments, including adaptation to saline-alkali habitats. Thus, lichens are pioneer species on saline-alkali soil. However, the separate resilience of the two symbiotic partners under saline-alkali conditions remains insufficiently understood. In this study, two representative symbiotic algae, Diplosphaera chodatii and Trebouxia jamesii, were studied for their physiological response to the saline-alkali stress by adjusting different concentrations of NaHCO3, together with their respective symbiotic fungi Endocarpon pusillum (terricolous lichen) and Umbilicaria muhlenbergii (saxicolous lichen). The results indicate that cell growth rate and biomass in all four cultures decreased in alkali-alkaline substrate, while cellular activities and ultrastructure were affected to a distinct extent. Compared with the symbiotic fungi, the algae were found to be more active in coordinating oxidative stress and lipid peroxidation damage under the saline-alkali stress. The antioxidant system of the alga was especially shown as a key adaptive trait and it provides an important strategy for species survival and persistence in arid saline-alkali desert. The specific survival ability of the lichen symbiosis relies on the stress resilience advantages of the symbiotic partners in combination. Our study provided new insights into understanding the adaptation of lichen symbiosis to desert saline-alkali soil, and the potential of lichen symbiotic algae in the future desert ecological restoration.

From phenotyping to genetic mapping: identifying water-stress adaptations in legume root traits.

BACKGROUND: Climate change induces perturbation in the global water cycle, profoundly impacting water availability for agriculture and therefore global food security. Water stress encompasses both drought (i.e. water scarcity) that causes the drying of soil and subsequent plant desiccation, and flooding, which results in excess soil water and hypoxia for plant roots. Terrestrial plants have evolved diverse mechanisms to cope with soil water stress, with the root system serving as the first line of defense. The responses of roots to water stress can involve both structural and physiological changes, and their plasticity is a vital feature of these adaptations. Genetic methodologies have been extensively employed to identify numerous genetic loci linked to water stress-responsive root traits. This knowledge is immensely important for developing crops with optimal root systems that enhance yield and guarantee food security under water stress conditions. RESULTS: This review focused on the latest insights into modifications in the root system architecture and anatomical features of legume roots in response to drought and flooding stresses. Special attention was given to recent breakthroughs in understanding the genetic underpinnings of legume root development under water stress. The review also described various root phenotyping techniques and examples of their applications in different legume species. Finally, the prevailing challenges and prospective research avenues in this dynamic field as well as the potential for using root system architecture as a breeding target are discussed. CONCLUSIONS: This review integrated the latest knowledge of the genetic components governing the adaptability of legume roots to water stress, providing a reference for using root traits as the new crop breeding targets.

Lessons from Extremophiles: Functional Adaptations and Genomic Innovations across the Eukaryotic Tree of Life.

From hydrothermal vents, to glaciers, to deserts, research in extreme environments has reshaped our understanding of how and where life can persist. Contained within the genomes of extremophilic organisms are the blueprints for a toolkit to tackle the multitude of challenges of survival in inhospitable environments. As new sequencing technologies have rapidly developed, so too has our understanding of the molecular and genomic mechanisms that have facilitated the success of extremophiles. Although eukaryotic extremophiles remain relatively understudied compared to bacteria and archaea, an increasing number of studies have begun to leverage 'omics tools to shed light on eukaryotic life in harsh conditions. In this perspective paper, we highlight a diverse breadth of research on extremophilic lineages across the eukaryotic tree of life, from microbes to macrobes, that are collectively reshaping our understanding of molecular innovations at life's extremes. These studies are not only advancing our understanding of evolution and biological processes but are also offering a valuable roadmap on how emerging technologies can be applied to identify cellular mechanisms of adaptation to cope with life in stressful conditions, including high and low temperatures, limited water availability, and heavy metal habitats. We shed light on patterns of molecular and organismal adaptation across the eukaryotic tree of life and discuss a few promising research directions, including investigations into the role of horizontal gene transfer in eukaryotic extremophiles and the importance of increasing phylogenetic diversity of model systems.

A trade-off in evolution: the adaptive landscape of spiders without venom glands.

BACKGROUND: Venom glands play a key role in the predation and defense strategies of almost all spider groups. However, the spider family Uloboridae lacks venom glands and has evolved an adaptive strategy: they excessively wrap their prey directly with spider silk instead of paralyzing it first with toxins. This shift in survival strategy is very fascinating, but the genetic underpinnings behind it are poorly understood. RESULTS: Spanning multiple spider groups, we conducted multiomics analyses on Octonoba sinensis and described the adaptive evolution of the Uloboridae family at the genome level. We observed the coding genes of myosin and twitchin in muscles are under positive selection, energy metabolism functions are enhanced, and gene families related to tracheal development and tissue mechanical strength are expanded or emerged, all of which are related to the unique anatomical structure and predatory behavior of spiders in the family Uloboridae. In addition, we also scanned the elements that are absent or under relaxed purifying selection, as well as toxin gene homologs in the genomes of 2 species in this family. The results show that the absence of regions and regions under relaxed selection in these spiders' genomes are concentrated in areas related to development and neurosystem. The search for toxin homologs reveals possible gene function shift between toxins and nontoxins and confirms that there are no reliable toxin genes in the genome of this group. CONCLUSIONS: This study demonstrates the trade-off between different predation strategies in spiders, using either chemical or physical strategy, and provides insights into the possible mechanism underlying this trade-off. Venomless spiders need to mobilize multiple developmental and metabolic pathways related to motor function and limb mechanical strength to cover the decline in adaptability caused by the absence of venom glands.

Metabolic adaptations underpin high productivity rates in relict subsurface water.

Groundwater aquifers are ecological hotspots with diverse microbes essential for biogeochemical cycles. Their ecophysiology has seldom been studied on a basin scale. In particular, our knowledge of chemosynthesis in the deep aquifers where temperatures reach 60 °C, is limited. Here, we investigated the diversity, activity, and metabolic potential of microbial communities from nine wells reaching ancient groundwater beneath Israel's Negev Desert, spanning two significant, deep (up to 1.5 km) aquifers, the Judea Group carbonate and Kurnub Group Nubian sandstone that contain fresh to brackish, hypoxic to anoxic water. We estimated chemosynthetic productivity rates ranging from 0.55 ± 0.06 to 0.82 ± 0.07 µg C L-1 d-1 (mean ± SD), suggesting that aquifer productivity may be underestimated. We showed that 60% of MAGs harbored genes for autotrophic pathways, mainly the Calvin-Benson-Bassham cycle and the Wood-Ljungdahl pathway, indicating a substantial chemosynthetic capacity within these microbial communities. We emphasize the potential metabolic versatility in the deep subsurface, enabling efficient carbon and energy use. This study set a precedent for global aquifer exploration, like the Nubian Sandstone Aquifer System in the Arabian and Western Deserts, and reconsiders their role as carbon sinks.

Electroencephalography microstate alterations reflect potential double-edged cognitive adaptation in Ménière's disease.

PURPOSE: To explore the microstate characteristics and underlying brain network activity of Ménière's disease (MD) patients based on high-density electroencephalography (EEG), elucidate the association between microstate dynamics and clinical manifestation, and explore the potential of EEG microstate features as future neurobiomarkers for MD. METHODS: Thirty-two patients diagnosed with MD and 29 healthy controls (HC) matched for demographic characteristics were included in the study. Dysfunction and subjective symptom severity were assessed by neuropsychological questionnaires, pure tone audiometry, and vestibular function tests. Resting-state EEG recordings were obtained using a 256-channel EEG system, and the electric field topographies were clustered into four dominant microstate classes (A, B, C, and D). The dynamic parameters of each microstate were analyzed and utilized as input for a support vector machine (SVM) classifier to identify significant microstate signatures associated with MD. The clinical significance was further explored through Spearman correlation analysis. RESULTS: MD patients exhibited an increased presence of microstate class C and a decreased frequency of transitions between microstate class A and B, as well as between class A and D. The transitions from microstate class A to C were also elevated. Further analysis revealed a positive correlation between equilibrium scores and the transitions from microstate class A to C under somatosensory challenging conditions. Conversely, transitions between class A and B were negatively correlated with vertigo symptoms. No significant correlations were detected between these characteristics and auditory test results or emotional scores. Utilizing the microstate features identified via sequential backward selection, the linear SVM classifier achieved a sensitivity of 86.21% and a specificity of 90.61% in distinguishing MD patients from HC. CONCLUSIONS: We identified several EEG microstate characteristics in MD patients that facilitate postural control yet exacerbate subjective symptoms, and effectively discriminate MD from HC. The microstate features may offer a new approach for optimizing cognitive compensation strategies and exploring potential neurobiological markers in MD.

The first high-altitude autotetraploid haplotype-resolved genome assembled (Rhododendron nivale subsp. boreale) provides new insights into mountaintop adaptation.

BACKGROUND: Rhododendron nivale subsp. boreale Philipson et M. N. Philipson is an alpine woody species with ornamental qualities that serve as the predominant species in mountainous scrub habitats found at an altitude of ∼4,200 m. As a high-altitude woody polyploid, this species may serve as a model to understand how plants adapt to alpine environments. Despite its ecological significance, the lack of genomic resources has hindered a comprehensive understanding of its evolutionary and adaptive characteristics in high-altitude mountainous environments. FINDINGS: We sequenced and assembled the genome of R. nivale subsp. boreale, an assembly of the first subgenus Rhododendron and the first high-altitude woody flowering tetraploid, contributing an important genomic resource for alpine woody flora. The assembly included 52 pseudochromosomes (scaffold N50 = 42.93 Mb; BUSCO = 98.8%; QV = 45.51; S-AQI = 98.69), which belonged to 4 haplotypes, harboring 127,810 predicted protein-coding genes. Conjoint k-mer analysis, collinearity assessment, and phylogenetic investigation corroborated autotetraploid identity. Comparative genomic analysis revealed that R. nivale subsp. boreale originated as a neopolyploid of R. nivale and underwent 2 rounds of ancient polyploidy events. Transcriptional expression analysis showed that differences in expression between alleles were common and randomly distributed in the genome. We identified extended gene families and signatures of positive selection that are involved not only in adaptation to the mountaintop ecosystem (response to stress and developmental regulation) but also in autotetraploid reproduction (meiotic stabilization). Additionally, the expression levels of the (group VII ethylene response factor transcription factors) ERF VIIs were significantly higher than the mean global gene expression. We suspect that these changes have enabled the success of this species at high altitudes. CONCLUSIONS: We assembled the first high-altitude autopolyploid genome and achieved chromosome-level assembly within the subgenus Rhododendron. In addition, a high-altitude adaptation strategy of R. nivale subsp. boreale was reasonably speculated. This study provides valuable data for the exploration of alpine mountaintop adaptations and the correlation between extreme environments and species polyploidization.

Generational stability of epigenetic transgenerational inheritance facilitates adaptation and evolution.

The epigenome and epigenetic inheritance were not included in the original modern synthesis theory or more recent extended evolutionary synthesis of evolution. In a broad range of species, the environment has been shown to play a significant role in natural selection, which more recently has been shown to occur through epigenetic alterations and epigenetic inheritance. However, even with this evidence, the field of epigenetics and epigenetic inheritance has been left out of modern evolutionary synthesis, as well as other current evolutionary models. Epigenetic mechanisms can direct the regulation of genetic processes (e.g. gene expression) and also can be directly changed by the environment. In contrast, DNA sequence cannot be directly altered by the environment. The goal of this review is to present the evidence of how epigenetics and epigenetic inheritance can alter phenotypic variation in numerous species. This can occur at a significantly higher frequency than genetic change, so correlates with the frequency of evolutionary change. In addition, the concept and importance of generational stability of transgenerational inheritance is incorporated into evolutionary theory. For there to be a better understanding of evolutionary biology, we must incorporate all aspects of molecular (e.g. genetics and epigenetics) and biological sciences (e.g. environment and adaptation).

Pulmonary adaptation to repeated poly(I:C) exposure is impaired in asthmatic mice: an observational study.

BACKGROUND: While asthma exacerbations remain a major challenge in patient management, few animal models exist to explore the underlying mechanisms. Here, we established an animal model of asthma that can be used to study pathophysiological mechanisms and therapeutic strategies on asthma exacerbation. METHODS: Female BALB/c mice were sensitized and exposed to PBS or Dermatophagoides pteronyssinus (DerP) extract for 11 weeks. Asthmatic phenotype was assessed through lung inflammation, bronchial hyperresponsiveness and bronchial smooth muscle remodeling. Asthmatic and control mice were exposed once or three times to poly(I:C) to simulate virus-induced inflammation. RESULTS: Fourteen days after exposure to DerP, asthmatic mice showed resolution of inflammation with sustained bronchial hyperresponsiveness and bronchial smooth muscle remodeling compared to control. At this stage, when mice were subjected to a single exposure to poly(I:C), control and asthmatic mice were characterized by a significant increase in neutrophilic inflammation and bronchial hyperresponsiveness. When mice were repeatedly exposed to poly(I:C), control mice showed a significant decrease in neutrophilic inflammation and bronchial hyperresponsiveness, while asthmatic mice experienced worsening of these outcomes. CONCLUSIONS: This observational study report an asthmatic mouse model that can undergo exacerbation after repeated exposure to poly(I:C). Our findings on pulmonary adaptation in control mice may also pave the way for further research into the mechanism of adaptation that may be impaired in asthma and raise the question of whether asthma exacerbation may be a loss of adaptation.