Chromosome-level genome assembly of Guide Black-Fur sheep (Ovis aries).

Guide Black-Fur sheep (GD) is a breed of Tibetan sheep (Ovis aries) that lives in the Qinghai-Tibetan plateau region at an altitude of over 4,000 m. However, a lack of genomic information has made it difficult to understand the high-altitude adaptation of these sheep. We sequenced and assembled the GD reference genome using PacBio, Hi-C, and Illumina sequencing technologies. The final assembled genome size was 2.73 Gb, with a contig N50 of 20.30 Mb and a scaffold N50 of 107.63 Mb. The genome is predicted to contain 20,759 protein-coding genes, of which 98.42 have functional annotations. Repeat elements account for approximately 52.2% of the genomic landscape. The completeness of the GD genome assembly is highlighted by a BUSCO score of 93.1%. This high-quality genome assembly provides a critical resource for future molecular breeding and genetic improvement of Tibetan sheep.

Granulation-embedded autologous skin grafting improves healing chronic wounds at high altitudes: a pilot study.

BACKGROUND: The management of chronic wounds presents a challenge for surgeons. In this pilot study, the authors established a novel auto-grafting approach for chronic wounds and evaluated its efficacy. PURPOSE: The objective of this pilot study was to observe the clinical efficacy of granulation-embedded skin grafting for the treatment of chronic wounds at high altitudes. METHODS: The data of 45 patients with chronic wounds were obtained from the medical records of the Yushu People's Hospital. Patients were divided into stamp skin-grafting and granulation-embedded skin-grafting groups. Skin graft survival rate, wound coverage rate, and wound-healing time were observed and recorded. The length of hospital stay and 1% total body surface area (TBSA) treatment cost were compared. RESULTS: Significant differences were noted in skin graft survival rate (94% ± 3% vs 86% ± 3%, P < .01), wound coverage rate on postoperative day 7 (61% ± 16% vs 54% ± 18%, P < .01), and wound-healing times (23 ± 2.52 days vs 31 ± 3.61 days, P < .05). The length of hospital stay and 1% TBSA treatment cost were significantly reduced in the granulation-embedded skin grafting group (P < .05). CONCLUSIONS: Granulation-embedded skin grafting can improve the healing of chronic wounds at high altitudes. These findings provide a new approach to the clinical treatment of chronic wounds.

Impact of high-altitude hypoxia on Helicobacter pylori-induced gastritis pathological manifestations and inflammatory responses.

BACKGROUND: Chronic gastritis caused by Helicobacter pylori (Hp) infection is a common gastrointestinal disorder. Despite the high prevalence of Hp infection and chronic gastritis in the Tibetan Plateau, there is a lack of studies elucidating the influence of plateau hypoxia on Hp-induced gastritis. This study aimed to investigate the impact of high-altitude hypoxia on Hp-induced gastritis, particularly focusing on pathological manifestations and inflammatory responses. METHODS: This study was conducted from July 2023 to March 2024 at the Department of Gastroenterology, Affiliated Hospital of Qinghai University. Ninety patients diagnosed with chronic gastritis were enrolled in the study and divided into four groups based on their residential altitude and Hp infection status. Data on endoscopic and pathological characteristics were collected, along with serum oxidative stress and inflammatory markers. RESULTS: Patients with Hp gastritis exhibit distinctive features in the gastric mucosa, including diffuse erythema, enlarged folds, and white turbid mucus during endoscopy. Notably, individuals with Hp gastritis at high altitudes show a higher prevalence of diffuse erythema and enlarged folds. Pathological analysis reveals that these patients have elevated gastric mucosal inflammation scores and increased chronic and active inflammation. Furthermore, individuals with Hp gastritis at high altitudes demonstrate elevated levels of serum TNF-α, IL-1ß, IL-6, and MDA, as well as reduced serum SOD and GSH-Px activities. CONCLUSIONS: High-altitude hypoxia may exacerbate gastric mucosal damage by enhancing oxidative stress and inflammatory response induced by Hp infection.

Oxygen Saturation Curve Analysis in 2298 Hypoxia Awareness Training Tests of Military Aircrew Members in a Hypobaric Chamber.

We aim to provide reference values for military aircrews participating in hypoxia awareness training (HAT). We describe several parameters with potential biomedical interest based on selected segments and slopes of the changes in oxygen saturation (SatO2) during a standard HAT. A retrospective analysis of 2298 records of the SatO2 curve was performed, including 1526 military men aged 30.48 ± 6.47 years during HAT in a hypobaric chamber. HAT consisted of pre-oxygenation at 100% and an ascent to 7620 m, followed by O2 disconnection starting the phase of descent of SatO2 until reaching the time of useful consciousness (TUC), and finally reconnection to 100% O2 in the recovery phase. Using an ad hoc computational procedure, the time taken to reach several defined critical values was computed. These key parameters were the time until desaturation of 97% and 90% (hypoxia) after oxygen mask disconnection (D97/D90) and reconnection (R97/R90) phases, the time of desaturation (TUC-D97) and hypoxia (TUC-D90) during disconnection, the total time in desaturation (L97) or hypoxia (L90), and the slopes of SatO2 drop (SDSAT97 and SDSAT90) and recovery (SRSAT97). The mean of the quartiles according to TUC were compared by ANOVA. The correlations between the different parameters were studied using Pearson's test and the effect size was estimated with ω2. Potentially useful parameters for the HAT study were those with statistical significance (p < 0.05) and a large effect size. D97, D90, R97, and R90 showed significant differences with small effect sizes, while TUC-D97, TUC-D90, L97, L90, and SDSAT97 showed significant differences and large effect sizes. SDSAT97 correlated with TUC (R = 0.79), TUC-D97 (R = 0.81), and TUC-D90 (R = 0.81). In conclusion, several parameters of the SatO2 curve are useful for the study and monitoring of HAT. The SDSAT97 measured during the test can estimate the TUC and thus contribute to taking measures to characterize and protect the aircrew members.

Whole-exome sequencing of individuals from an isolated population under extreme conditions implicates rare risk variants of schizophrenia.

Schizophrenia (SCZ), which affects approximately 1% of the world's population, is a global public health concern. It is generally considered that the interplay between genes and the environment is important in the onset and/or development of SCZ. Although several whole-exome sequencing studies have revealed rare risk variants of SCZ, no rare coding variants have been strongly replicated. Assessing isolated populations under extreme conditions might lead to the discovery of variants with a recent origin, which are more likely to have a higher frequency than chance to reflect gene-environment interactions. Following this approach, we examined a unique cohort of Tibetans living at an average altitude above 4500 meters. Whole-exome sequencing of 47 SCZ cases and 53 controls revealed 275 potential novel risk variants and two known variants (12:46244485: A/G and 22:18905934: A/G) associated with SCZ that were found in existing databases. Only one gene (C5orf42) in the gene-based statistics surpassed the exome-wide significance in the cohort. Metascape enrichment analysis suggested that novel risk genes were strongly enriched in pathways relevant to hypoxia, neurodevelopment, and neurotransmission. Additionally, 47 new risk genes were followed up in Han sample of 279 patients with SCZ and 95 controls, only BAI2 variant appearing in one case. Our findings suggest that SCZ patients living at high altitudes may have a unique risk gene signature, which may provide additional information on the underlying biology of SCZ, which can be exploited to identify individuals at greater risk of exposure to hypoxia.

Effect of cold arid high-altitude environment on bioactive phytochemical compounds of organically grown Brassicaceae vegetables for nutri-health security in mountainous regions.

High-altitude (HA) environment presents immense physiological adversities for humans that have been overcome by supplementing bio-active phytochemicals from functional foods that support and accelerate acclimatization under these extreme environmental conditions. Several agricultural interventions have been investigated to enhance the phytochemical content in vegetables however; these studies have been limited to low-altitude (LA) regions only. In view of an existing knowledge gap, current work is designed to compare the phytochemical compositions of HA and LA-grown Brassicaceae vegetables (cabbage, cauliflower, knol-khol, and radish) using organic treatments via farm yard manure (FYM) and Azotobacter. The open field study was conducted as a two-factorial randomized block design. The first factor was treatment (T1-FYM, T2-Azotobacter, T3-FYM + Azotobacter, and T4-control) while the second was locations (HA and LA). Among all these treatments, the application of treatment T3 in HA-grown cabbage showed the highest total phenolic content (TPC; 9.56 µg/mg), total flavonoids content (TFC; 14.48 µg/mg), and antioxidant potential using 2,2-diphenyl-1-picrylhydrazyl (DPPH; 85.97%) and ferric reducing antioxidant power (FRAP; 30.77 µg/mg) compared to LA grown samples. Reverse Phase high performance liquid chromatography (RP-HPLC) analysis showed that treatment T3 at HA led to significantly high kaempferol (0.92 µg/mg) and sulforaphane (8.94 µg/mg) contents in cabbage whereas, indole-3-carbinol (1.31 µg/mg) was higher in HA grown cauliflower. The present study provides scientific evidence for the enrichment of health-promoting phytochemical compounds in Brassicaceae vegetables grown with T3 treatment specifically at HA.

Cardiovascular effects of breath-hold diving at altitude.

Hypoxia, centralization of blood in pulmonary vessels, and increased cardiac output during physical exertion are the pathogenetic pathways of acute pulmonary edema observed during exposure to extraordinary environments. This study aimed to evaluate the effects of breath-hold diving at altitude, which exposes simultaneously to several of the stimuli mentioned above. To this aim, 11 healthy male experienced divers (age 18-52y) were evaluated (by Doppler echocardiography, lung echography to evaluate ultrasound lung B-lines (BL), hemoglobin saturation, arterial blood pressure, fractional NO (Nitrous Oxide) exhalation in basal condition (altitude 300m asl), at altitude (2507m asl) and after breath-hold diving at altitude. A significant increase in E/e' ratio (a Doppler-echocardiographic index of left atrial pressure) was observed at altitude, with no further change after the diving session. The number of BL significantly increased after diving at altitude as compared to basal conditions. Finally, fractional exhaled nitrous oxide was significantly reduced by altitude; no further change was observed after diving. Our results suggest that exposure to hypoxia may increase left ventricular filling pressure and, in turn, pulmonary capillary pressure. Breath-hold diving at altitude may contribute to interstitial edema (as evaluated by BL score), possibly because of physical efforts made during a diving session. The reduction of exhaled nitrous oxide at altitude confirms previous reports of nitrous oxide reduction after repeated exposure to hypoxic stimuli. This finding should be further investigated since reduced nitrous oxide production in hypoxic conditions has been reported in subjects prone to high-altitude pulmonary edema.

[Research progress of traditional Chinese and Western medicine non-pharmacological prevention strategies for acute high altitude disease].

Acute high altitude disease (AHAD) is a general term for a series of clinical reactions that occur when the body fails to adapt to the low-pressure hypoxic environment of high altitudes. Mild cases can cause symptoms such as headache, nausea and vomiting, while more severe cases can lead to life-threatening conditions such as pulmonary edema, cerebral edema and other critical conditions that can be fatal. With the increasing demand for high altitudes deployment, understanding the common preventive measures of AHAD can reduce its morbidity or mortality to a certain extent, which is of great benefit to those who reside temporarily at high altitudes. In recent years, as people's health awareness has improved, there has been a growing attention towards non-pharmacological methods of disease prevention. At the same time, non-pharmacological therapy has significant therapeutic effects in preventing and treating high-altitude diseases, which has attracted the attention of researchers in this field. This review summarizes the major non-pharmacological preventive components of modern medicine and outlines the current non-pharmacological approaches to AHAD from the perspective of traditional Chinese medicine, intending to serve clinical purposes and improve the onset and prognosis of AHAD.

Work at high altitude and non-fatal cardiovascular disease associated with unfitness to work: Prospective cohort observation.

INTRODUCTION: Mining at high altitude exposes workers to hypoxic environment and cold climate in addition to conventional hazards in mining, but very little is known on how to define fitness to work in prospective candidates with pre-existing conditions. The aim of the current study was to define the incidence of cardiovascular diseases leading to unfitness to work as well as their predictors in a prospective observation. METHODS: A total of 569 prospective employees (median age 34 (interquartile range (IQR) 28;40) years, 95% men 85% mid-altitude residents) for a high-altitude gold mine in Kyrgyzstan operating at 3800-4500 meters above sea level were screened at pre-employment in 2009-2012 and followed by January 2022. Cox regression was used to quantify the association of baseline demographics and physiological variables with newly diagnosed cardiovascular diseases (CVD) leading to unfitness to work, expressed as hazard ratios (HRs) with 95% confidence intervals (CI). RESULTS: With 5190 person-years of observation, 155 (27%) workers have left work, of whom 23 had a newly identified CVD leading to unfitness to work (cumulative incidence 4%) with no difference between drivers and other occupations, despite greater blood pressure and body mass index (BMI) in the former at baseline. Age (HR 1.13 (95% CI 1.06;1.22) and BMI (HR 1.18 (95% CI 1.04;1.34)) were associated with a greater chance of having CVD, adjusted for lung function, baseline diagnoses, year of employment and baseline blood pressure. Narrowing the analysis to only men, drivers, smokers and even middle-altitude residents did not change the effect. CONCLUSION: These findings confirmed high efficacy of pre-employment screening limiting access of workers with advanced conditions to work which later yielded low CVD incidence. In addition to conventional contraindications to work at high altitude, age and high BMI should be considered when a decision is made.

Effects of temperature gradient on functional fruit traits: an elevation-for-temperature approach.

Fruit traits mediate animal-plant interactions and have to a large degree evolved to match the sensory capacities and morphology of their respective dispersers. At the same time, fruit traits are affected by local environmental factors, which may affect frugivore-plant trait match. Temperature has been identified as a major factor with a strong effect on the development of fruits, which is of serious concern because of the rising threat of global warming. Nonetheless, this primarily originates from studies on domesticated cultivars in often controlled environments. Little is known on the effect of rising temperatures on fruit traits of wild species and the implications this could have to seed dispersal networks, including downstream consequences to biodiversity and ecosystem functioning. In a case study of five plant species from eastern Madagascar, we addressed this using the elevation-for-temperature approach and examined whether a temperature gradient is systematically associated with variation in fruit traits relevant for animal foraging and fruit selection. We sampled across a gradient representing a temperature gradient of 1.5-2.6 °C, corresponding to IPCC projections. The results showed that in most cases there was no significant effect of temperature on the traits evaluated, although some species showed different effects, particularly fruit chemical profiles. This suggests that in these species warming within this range alone is not likely to drive substantial changes in dispersal networks. While no systemic effects were found, the results also indicate that the effect of temperature on fruit traits differs across species and may lead to mismatches in specific animal-plant interactions.

Short-term changes in chest CT images among individuals at low altitude after entering high-altitude environments.

Objective: To investigate the short-term changes in chest CT images of low-altitude populations after entering a high-altitude environment. Methods: Chest CT images of 3,587 people from low-altitude areas were obtained within one month of entering a high-altitude environment. Abnormal CT features and clinical symptoms were analyzed. Results: Besides acute high-altitude pulmonary edema, the incidence of soft tissue space pneumatosis was significantly higher than that in low-altitude areas. Pneumatosis was observed in the mediastinum, cervical muscle space, abdominal cavity, and spinal cord epidural space, especially the mediastinum. Conclusion: In addition to acute high-altitude pulmonary edema, spontaneous mediastinal emphysema often occurs when individuals in low-altitude areas adapt to the high-altitude environment of cold, low-pressure, and hypoxia. When the gas escapes to the abdominal cavity, it is easy to be misdiagnosed as gastrointestinal perforation. It is also not uncommon for gas accumulation to escape into the epidural space of the spinal cord. The phenomenon of gas diffusion into distant tissue space and the mechanism of gas escape needs to be further studied.

Prevalence and risk factors of deep venous thrombosis of hospitalizations in plateau: a cross-section analysis.

BACKGROUND: Deep venous thrombosis (DVT) is a serious public health issue that threatens human health and economic development. Presently, differences in the prevalence of DVT among individuals from different nationalities, residents of high-altitude areas, and those consuming any special diet are unknown. Therefore, we aimed to elucidate the prevalence of and the associated risk factors for DVT in hospitalized patients in the plateau areas. METHODS: The subjects were hospitalized patients in three grade III-a hospitals in the Qinghai Province, China, during January-October 2020. The demographic, clinical, and laboratory data were collected at admission, and ultrasonography of the bilateral lower extremities was performed. The hospital stay-duration was recorded at the time of discharge. RESULTS: A total of 3432 patients were enrolled, of which 159 (4.60%) were diagnosed with DVT. The age of > 50 years (OR = 2.434, 95% CI: 1.521-3.894252, P < 0.001), residence altitude of ≥ 3000 m (OR = 2.346, 95% CI: 1.239-4.440, P = 0.009), D-dimer level of ≥ 0.5 mg/L (OR = 2.211, 95% CI: 1.547-3.161, P < 0.001), presence of comorbidities (OR = 1.904, 95% CI: 1.386-2.705, P < 0.001), a history of varicose veins (OR = 1.990, 95% CI: 0.959-4.128, P = 0.045), and current medications (OR = 2.484, 95% CI: 1.778-3.471, P < 0.001) were identified as risk factors for DVT in these plateau areas. CONCLUSION: The prevalence of DVT in the hospitalized patients of the studied plateau areas was 4.60%. We recommend considering individualized risk stratification (age > 50 years, residence altitude ≥ 3000 m, a history of varicose veins, D-dimer level ≥ 0.5 mg/L, current medications, and comorbidities) for patients at the time of admission.

Experimental evidence of climate change extinction risk in Neotropical montane epiphytes.

Climate change is conjectured to endanger tropical species, particularly in biodiverse montane regions, but accurate estimates of extinction risk are limited by a lack of empirical data demonstrating tropical species' sensitivity to climate. To fill this gap, studies could match high-quality distribution data with multi-year transplant experiments. Here, we conduct field surveys of epiphyte distributions on three mountains in Central America and perform reciprocal transplant experiments on one mountain across sites that varied in elevation, temperature and aridity. We find that most species are unable to survive outside of their narrow elevational distributions. Additionally, our findings suggest starkly different outcomes from temperature conditions expected by 2100 under different climate change scenarios. Under temperatures associated with low-emission scenarios, most tropical montane epiphyte species will survive, but under emission scenarios that are moderately high, 5-36% of our study species may go extinct and 10-55% of populations may be lost. Using a test of tropical species' climate tolerances from a large field experiment, paired with detailed species distribution data across multiple mountains, our work strengthens earlier conjecture about risks of wide-spread extinctions from climate change in tropical montane ecosystems.

miRNA and leptin signaling in metabolic diseases and at extreme environments.

The burden of growing concern about the dysregulation of metabolic processes arises due to complex interplay between environment and nutrition that has great impact on genetics and epigenetics of an individual. Thereby, any abnormality at the level of food intake regulating hormones may contribute to the development of metabolic diseases in any age group due to malnutrition, overweight, changing lifestyle, and exposure to extreme environments such as heat stress (HS), cold stress, or high altitude (HA). Hormones such as leptin, adiponectin, ghrelin, and cholecystokinin regulate appetite and satiety to maintain energy homeostasis. Leptin, an adipokine and a pleiotropic hormone, play major role in regulating the food intake, energy gain and energy expenditure. Using in silico approach, we have identified the major genes (LEP, LEPR, JAK2, STAT3, NPY, POMC, IRS1, SOCS3) that play crucial role in leptin signaling pathway. Further, eight miRNAs (hsa-miR-204-5p, hsa-miR-211-5p, hsa-miR-30, hsa-miR-3163, hsa-miR-33a-3p, hsa-miR-548, hsa-miR-561-3p, hsa-miR-7856-5p) from TargetScan 8.0 database were screened out that commonly target these genes. The role of these miRNAs should be explored as they might play vital role in regulating the appetite, energy metabolism, metabolic diseases (obesity, type 2 diabetes, cardiovascular diseases, inflammation), and to combat extreme environments. The miRNAs regulating leptin signaling and appetite may be useful for developing novel therapeutics for metabolic diseases.

Effects of the Interaction between Rumen Microbiota Density-VFAs-Hepatic Gluconeogenesis on the Adaptability of Tibetan Sheep to Plateau.

During the adaptive evolution of animals, the host and its gut microbiota co-adapt to different elevations. Currently, there are few reports on the rumen microbiota-hepato-intestinal axis of Tibetan sheep at different altitudes. Therefore, the purpose of this study was to explore the regulatory effect of rumen microorganism-volatile fatty acids (VFAs)-VFAs transporter gene interactions on the key enzymes and genes related to gluconeogenesis in Tibetan sheep. The rumen fermentation parameters, rumen microbial densities, liver gluconeogenesis activity and related genes were determined and analyzed using gas chromatography, RT-qPCR and other research methods. Correlation analysis revealed a reciprocal relationship among rumen microflora-VFAs-hepatic gluconeogenesis in Tibetan sheep at different altitudes. Among the microbiota, Ruminococcus flavefaciens (R. flavefaciens), Ruminococcus albus (R. albus), Fibrobactersuccinogenes and Ruminobacter amylophilus (R. amylophilus) were significantly correlated with propionic acid (p < 0.05), while propionic acid was significantly correlated with the transport genes monocarboxylate transporter 4 (MCT4) and anion exchanger 2 (AE2) (p < 0.05). Propionic acid was significantly correlated with key enzymes such as pyruvate carboxylase, phosphoenolpyruvic acid carboxylase and glucose (Glu) in the gluconeogenesis pathway (p < 0.05). Additionally, the expressions of these genes were significantly correlated with those of the related genes, namely, forkhead box protein O1 (FOXO1) and mitochondrial phosphoenolpyruvate carboxykinase 2 (PCK2) (p < 0.05). The results showed that rumen microbiota densities differed at different altitudes, and the metabolically produced VFA contents differed, which led to adaptive changes in the key enzyme activities of gluconeogenesis and the expressions of related genes.

Exploring the interplay between angiosperm chlorophyll metabolism and environmental factors.

MAIN CONCLUSION: In this review, we summarize how chlorophyll metabolism in angiosperm is affected by the environmental factors: light, temperature, metal ions, water, oxygen, and altitude. The significance of chlorophyll (Chl) in plant leaf morphogenesis and photosynthesis cannot be overstated. Over time, researchers have made significant advancements in comprehending the biosynthetic pathway of Chl in angiosperms, along with the pivotal enzymes and genes involved in this process, particularly those related to heme synthesis and light-responsive mechanisms. Various environmental factors influence the stability of Chl content in angiosperms by modulating Chl metabolic pathways. Understanding the interplay between plants Chl metabolism and environmental factors has been a prominent research topic. This review mainly focuses on angiosperms, provides an overview of the regulatory mechanisms governing Chl metabolism, and the impact of environmental factors such as light, temperature, metal ions (iron and magnesium), water, oxygen, and altitude on Chl metabolism. Understanding these effects is crucial for comprehending and preserving the homeostasis of Chl metabolism.

Environmental fate of microplastics in high-altitude basins: the insights into the Yarlung Tsangpo River Basin.

Microplastics (MPs) have been found in remote high-altitude areas, but the main source and migration process remained unclear. This work explored the characteristics and potential sources of MPs in the Yarlung Tsangpo River Basin. The average abundances of MPs in water, sediment, and soil samples were 728.26 ± 100.53 items/m3, 43.16 ± 5.82 items/kg, and 61.92 ± 4.29 items/kg, respectively, with polypropylene and polyethylene as the main polymers. The conditional fragmentation model revealed that the major source of MPs lower than 4000 m was human activities, while that of higher than 4500 m was atmospheric deposition. Community analysis was further conducted to explore the migration process and key points of MPs among different compartments in the basin. It was found that Lhasa (3600 m) and Shigatse (4100 m) were vital sources of MPs inputs in the midstream and downstream, respectively. This work would provide new insights into the fate of MPs in high-altitude areas.

Ancient Plasmodium genomes shed light on the history of human malaria.

Malaria-causing protozoa of the genus Plasmodium have exerted one of the strongest selective pressures on the human genome, and resistance alleles provide biomolecular footprints that outline the historical reach of these species1. Nevertheless, debate persists over when and how malaria parasites emerged as human pathogens and spread around the globe1,2. To address these questions, we generated high-coverage ancient mitochondrial and nuclear genome-wide data from P. falciparum, P. vivax and P. malariae from 16 countries spanning around 5,500 years of human history. We identified P. vivax and P. falciparum across geographically disparate regions of Eurasia from as early as the fourth and first millennia BCE, respectively; for P. vivax, this evidence pre-dates textual references by several millennia3. Genomic analysis supports distinct disease histories for P. falciparum and P. vivax in the Americas: similarities between now-eliminated European and peri-contact South American strains indicate that European colonizers were the source of American P. vivax, whereas the trans-Atlantic slave trade probably introduced P. falciparum into the Americas. Our data underscore the role of cross-cultural contacts in the dissemination of malaria, laying the biomolecular foundation for future palaeo-epidemiological research into the impact of Plasmodium parasites on human history. Finally, our unexpected discovery of P. falciparum in the high-altitude Himalayas provides a rare case study in which individual mobility can be inferred from infection status, adding to our knowledge of cross-cultural connectivity in the region nearly three millennia ago.

Telomeric RNA (TERRA) increases in response to spaceflight and high-altitude climbing.

Telomeres are repetitive nucleoprotein complexes at chromosomal termini essential for maintaining genome stability. Telomeric RNA, or TERRA, is a previously presumed long noncoding RNA of heterogeneous lengths that contributes to end-capping structure and function, and facilitates telomeric recombination in tumors that maintain telomere length via the telomerase-independent Alternative Lengthening of Telomeres (ALT) pathway. Here, we investigated TERRA in the radiation-induced DNA damage response (DDR) across astronauts, high-altitude climbers, healthy donors, and cellular models. Similar to astronauts in the space radiation environment and climbers of Mt. Everest, in vitro radiation exposure prompted increased transcription of TERRA, while simulated microgravity did not. Data suggest a specific TERRA DDR to telomeric double-strand breaks (DSBs), and provide direct demonstration of hybridized TERRA at telomere-specific DSB sites, indicative of protective TERRA:telomeric DNA hybrid formation. Targeted telomeric DSBs also resulted in accumulation of TERRA foci in G2-phase, supportive of TERRA's role in facilitating recombination-mediated telomere elongation. Results have important implications for scenarios involving persistent telomeric DNA damage, such as those associated with chronic oxidative stress (e.g., aging, systemic inflammation, environmental and occupational radiation exposures), which can trigger transient ALT in normal human cells, as well as for targeting TERRA as a therapeutic strategy against ALT-positive tumors.

High-elevation-induced decrease in soil pH weakens ecosystem multifunctionality by influencing soil microbiomes.

Plant environmental stress response has become a global research hotspot, yet there is a lack of clear understanding regarding the mechanisms that maintain microbial diversity and their ecosystem services under environmental stress. In our research, we examined the effects of moderate elevation on the rhizosphere soil characteristics, microbial community composition, and ecosystem multifunctionality (EMF) within agricultural systems. Our findings revealed a notable negative correlation between EMF and elevation, indicating a decline in multifunctionality at higher elevations. Additionally, our analysis across bacterial and protistan communities showed a general decrease in microbial richness with increasing elevation. Using random forest models, pH was identified as the key environmental stressor influencing microbial communities. Furthermore, we found that microbial community diversity is negatively correlated with stability by mediating complexity. Interestingly, while pH was found to affect the complexity within bacterial networks, it did not significantly impact the ecosystem stability along the elevation gradients. Using a Binary-State Speciation and Extinction (BiSSE) model to explore the evolutionary dynamics, we found that Generalists had higher speciation rates and lower extinction rates compared to specialists, resulting in a skewed distribution towards higher net diversification for generalists under increasing environmental stress. Moreover, structural equation modeling (SEM) analysis highlighted a negative correlation between environmental stress and community diversity, but showed a positive correlation between environmental stress and degree of cooperation & competition. These interactions under environmental stress indirectly increased community stability and decreased multifunctionality. Our comprehensive study offers valuable insights into the intricate relationship among environmental factors, microbial communities, and ecosystem functions, especially in the context of varying elevation gradients. These findings contribute significantly to our understanding of how environmental stressors affect microbial diversity and ecosystem services, providing a foundation for future ecological research and management strategies in similar contexts.