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Scientific Reports Jun 2024Anthropological and biophysical processes have shaped livestock genomes over Millenia and can explain their current geographic distribution and genetic divergence. We...
Anthropological and biophysical processes have shaped livestock genomes over Millenia and can explain their current geographic distribution and genetic divergence. We analyzed 57 Ethiopian indigenous domestic goat genomes alongside 67 equivalents of east, west, and north-west African, European, South Asian, Middle East, and wild Bezoar goats. Cluster, ADMIXTURE (K = 4) and phylogenetic analysis revealed four genetic groups comprising African, European, South Asian, and wild Bezoar goats. The Middle Eastern goats had an admixed genome of these four genetic groups. At K = 5, the West African Dwarf and Moroccan goats were separated from East African goats demonstrating a likely historical legacy of goat arrival and dispersal into Africa via the coastal Mediterranean Sea and the Horn of Africa. F, XP-EHH, and Hp analysis revealed signatures of selection in Ethiopian goats overlaying genes for thermo-sensitivity, oxidative stress response, high-altitude hypoxic adaptation, reproductive fitness, pathogen defence, immunity, pigmentation, DNA repair, modulation of renal function and integrated fluid and electrolyte homeostasis. Notable examples include TRPV1 (a nociception gene); PTPMT1 (a critical hypoxia survival gene); RETREG (a regulator of reticulophagy during starvation), and WNK4 (a molecular switch for osmoregulation). These results suggest that human-mediated translocations and adaptation to contrasting environments are shaping indigenous African goat genomes.
Topics: Animals; Goats; Ethiopia; Genome; Phylogeny; Stress, Physiological; Genetic Variation
PubMed: 38942813
DOI: 10.1038/s41598-024-65303-x -
Phytomedicine : International Journal... Jun 2024Hypoxic pulmonary vascular remodeling (HPVR) is a key pathological feature of hypoxic pulmonary hypertension (HPH). Oxygen-sensitive potassium (K) channels in pulmonary...
BACKGROUND
Hypoxic pulmonary vascular remodeling (HPVR) is a key pathological feature of hypoxic pulmonary hypertension (HPH). Oxygen-sensitive potassium (K) channels in pulmonary artery smooth muscle cells (PASMCs) play a crucial role in HPVR. Luteolin (Lut) is a plant-derived flavonoid compound with variety of pharmacological actions. Our previous study found Lut alleviated HPVR in HPH rat.
PURPOSE
To elucidate the mechanism by which Lut mitigated HPVR, focusing on oxygen-sensitive voltage-dependent potassium channel 1.5 (Kv1.5).
METHODS
HPH rat model was established using hypobaric chamber to simulate 5000 m altitude. Isolated perfused/ventilated rat lung, isolated pulmonary arteriole ring was utilized to investigate the impact of Lut on K channels activity. Kv1.5 level in lung tissue and pulmonary arteriole of HPH rat was assessed. CyclinD1, CDK4, PCNA, Bax, Bcl-2, cleaved caspase-3 levels in lung tissue of HPH rat were tested. The effect of Lut on Kv1.5, cytoplasmic free calcium concentration ([Ca]), CyclinD1, CDK4, PCNA, Bax/Bcl-2 was examined in PASMCs under hypoxia, with DPO-1 as a Kv1.5 specific inhibitor. The binding affinity between Lut and Kv1.5 in PASMCs was detected by drug affinity responsive target stability (DARTS). The overexpression of KCNA5 gene (encoding Kv1.5) in HEK293T cells was utilized to confirm the interaction between Lut and Kv1.5. Furthermore, the impact of Lut on mitochondrial structure, SOD, GSH, GSH-Px, MDA and HIF-1α levels were evaluated in lung tissue of HPH rat and PASMCs under hypoxia.
RESULTS
Lut dilated pulmonary artery by directly activating Kv and Ca-activated K channels (K) in smooth muscle. Kv1.5 level in lung tissue and pulmonary arteriole of HPH rat was upregulated by Lut. Lut downregulated CyclinD1, CDK4, PCNA while upregulating Bax/Bcl-2/caspase-3 axis in lung tissue of HPH rat. Lut decreased [Ca], reduced CDK4, CyclinD1, PCNA, increased Bax/Bcl-2 ratio, in PASMCs under hypoxia, by upregulating Kv1.5. The binding affinity and the interaction between Lut and Kv1.5 was verified in PASMCs and in HEK293T cells. Lut also decreased [Ca] and inhibited proliferation via targeting Kv1.5 of HEK293T cells under hypoxia. Furthermore, Lut protected mitochondrial structure, increased SOD, GSH, GSH-Px, decreased MDA, in lung tissue of HPH rat. Lut downregulated HIF-1α level in both lung tissue of HPH rat and PASMCs under hypoxia.
CONCLUSION
Lut alleviated HPVR by promoting vasodilation of pulmonary artery, reducing cellular proliferation, and inducing apoptosis through upregulating of Kv1.5 in PASMCs.
PubMed: 38941817
DOI: 10.1016/j.phymed.2024.155840 -
PloS One 2024Niche evolution refers to the process by which species undergo changes in ecological interactions, as well as their ability to disperse over time. Our study focuses on...
Niche evolution refers to the process by which species undergo changes in ecological interactions, as well as their ability to disperse over time. Our study focuses on the widely distributed neotropical genus of social wasps, Synoeca (Hymenoptera, Vespidae, Epiponini). We use ecological niche modeling to investigate the niche evolution of this insects, to explore how species have evolved within and across distinct environmental boundaries, as well as to explore the overlap, equivalence, and similarity between their niches. Our analysis of Predicted Niche Occupancy reveals that species occupy heterogeneous niches in relation to temperature, precipitation, and altitude, similar to the patterns observed in the analysis of the evolutionary history of climate tolerances, which shows that species have evolved to occupy distinct niche ranges. In addition, our niche comparisons indicate that the species do not share similar niches with each other. All these results suggest that Phylogenetic Niche Conservatism may be playing a significant role as a process contributing to the allopatric pattern observed in this genus. This study represents the first investigation of niche evolution in Vespidae, providing valuable insights for future research into the evolutionary dynamics of insects.
Topics: Animals; Wasps; Biological Evolution; Ecosystem; Phylogeny; Climate
PubMed: 38941328
DOI: 10.1371/journal.pone.0306204 -
Personalized Medicine Jun 2024High altitude pulmonary edema (HAPE) is a life-threatening form of non-cardiogenic pulmonary edema. In recent years, association studies have become the main method for...
High altitude pulmonary edema (HAPE) is a life-threatening form of non-cardiogenic pulmonary edema. In recent years, association studies have become the main method for identifying HAPE genetic loci. A genome-wide association study (GWAS) of HAPE risk-associated loci was performed in Chinese male Han individuals (164 HAPE cases and 189 healthy controls) by the Precision Medicine Diversity Array Chip with 2,771,835 loci (Applied Biosystems Axiom™). Eight overlapping candidate loci in , , and were finally selected. functional analyses displayed the PPI network, functional enrichment and signal pathways related to , , and . This study provides data supplements for HAPE susceptibility gene loci and new insights into HAPE susceptibility.
PubMed: 38940394
DOI: 10.1080/17410541.2024.2365617 -
International Journal of Molecular... Aug 2024The ubiquitin (Ub)‑proteasome system (UPS) plays a pivotal role in maintaining protein homeostasis and function to modulate various cellular processes including... (Review)
Review
The ubiquitin (Ub)‑proteasome system (UPS) plays a pivotal role in maintaining protein homeostasis and function to modulate various cellular processes including skeletal cell differentiation and bone homeostasis. The Ub ligase E3 promotes the transfer of Ub to the target protein, especially transcription factors, to regulate the proliferation, differentiation and survival of bone cells, as well as bone formation. In turn, the deubiquitinating enzyme removes Ub from modified substrate proteins to orchestrate bone remodeling. As a result of abnormal regulation of ubiquitination, bone cell differentiation exhibits disorder and then bone homeostasis is affected, consequently leading to osteoporosis. The present review discussed the role and mechanism of UPS in bone remodeling. However, the specific mechanism of UPS in the process of bone remodeling is still not fully understood and further research is required. The study of the mechanism of action of UPS can provide new ideas and methods for the prevention and treatment of osteoporosis. In addition, the most commonly used osteoporosis drugs that target ubiquitination processes in the clinic are discussed in the current review.
Topics: Humans; Osteoporosis; Ubiquitination; Animals; Ubiquitin; Proteasome Endopeptidase Complex; Bone Remodeling; Ubiquitin-Protein Ligases
PubMed: 38940355
DOI: 10.3892/ijmm.2024.5392 -
Current Drug Delivery Jun 2024Drug transporters are critical factors influencing the pharmacokinetics of drugs under hypoxic conditions. Studies have shown significant changes in drug transporter...
Drug transporters are critical factors influencing the pharmacokinetics of drugs under hypoxic conditions. Studies have shown significant changes in drug transporter levels in the hypoxic environment. In addition to being regulated by HIF-1, nuclear receptors, and inflammatory factors, hypoxia can also regulate transporters through epigenetic modifications, thereby affecting drug absorption, distribution, metabolism, and excretion. In recent years, increasing attention has been paid to the role of epigenetic modifications in regulating drug transporters under hypoxic conditions at high altitude. In this paper, we comprehensively review the effects of hypoxia on drug transporters and epigenetic modifications and explore the regulatory mechanism of epigenetic modifications on drug transporter expression under hypoxic conditions. The aim is to provide a reference for exploring the epigenetic regulation mechanism of drug transporter expression in the hypoxic environment at high altitude, and then guide the study of pharmacokinetics and promote effective and safe medication at high altitude.
PubMed: 38939986
DOI: 10.2174/0115672018295087240620061102 -
Frontiers in Plant Science 2024Biological nitrogen fixation (BNF) plays a crucial role in nitrogen utilization in agroecosystems. Functional characteristics of plants (grasses vs. legumes) affect BNF....
Legume-grass mixtures improve biological nitrogen fixation and nitrogen transfer by promoting nodulation and altering root conformation in different ecological regions of the Qinghai-Tibet Plateau.
INTRODUCTION
Biological nitrogen fixation (BNF) plays a crucial role in nitrogen utilization in agroecosystems. Functional characteristics of plants (grasses vs. legumes) affect BNF. However, little is still known about how ecological zones and cropping patterns affect legume nitrogen fixation. This study's objective was to assess the effects of different cropping systems on aboveground dry matter, interspecific relationships, nodulation characteristics, root conformation, soil physicochemistry, BNF, and nitrogen transfer in three ecological zones and determine the main factors affecting nitrogen derived from the atmosphere (Ndfa) and nitrogen transferred (Ntransfer).
METHODS
The N labeling method was applied. Oats ( L.), forage peas ( L.), common vetch ( L.), and fava beans ( L.) were grown in monocultures and mixtures (YS: oats and forage peas; YJ: oats and common vetch; YC: oats and fava beans) in three ecological regions (HZ: Huangshui Valley; GN: Sanjiangyuan District; MY: Qilian Mountains Basin) in a split-plot design.
RESULTS
The results showed that mixing significantly promoted legume nodulation, optimized the configuration of the root system, increased aboveground dry matter, and enhanced nitrogen fixation in different ecological regions. The percentage of nitrogen derived from the atmosphere (%Ndfa) and percentage of nitrogen transferred (%Ntransfer) of legumes grown with different legume types and in different ecological zones were significantly different, but mixed cropping significantly increased the %Ndfa of the legumes. Factors affecting Ndfa included the cropping pattern, the ecological zone (R), the root nodule number, pH, ammonium-nitrogen, nitrate-nitrogen, microbial nitrogen mass (MBN), plant nitrogen content (N%), and aboveground dry biomass. Factors affecting Ntransfer included R, temperature, altitude, root surface area, nitrogen-fixing enzyme activity, organic matter, total soil nitrogen, MBN, and N%.
DISCUSSION
We concluded that mixed cropping is beneficial for BNF and that mixed cropping of legumes is a sustainable and effective forage management practice on the Tibetan Plateau.
PubMed: 38938644
DOI: 10.3389/fpls.2024.1375166 -
JACC. Advances Dec 2023
PubMed: 38938486
DOI: 10.1016/j.jacadv.2023.100720 -
Experimental & Applied Acarology Jun 2024The adoption of the European Green Deal will limit acaricide use in high value crops like raspberry, to be replaced by biological control and other alternative...
The adoption of the European Green Deal will limit acaricide use in high value crops like raspberry, to be replaced by biological control and other alternative strategies. More basic knowledge on mites in such crops is then necessary, like species, density, and their role as vectors of plant diseases. This study had four aims, focusing on raspberry leaves at northern altitude: (1) identify mite species; (2) study mite population densities; (3) investigate mite intra-plant distribution; (4) investigate co-occurrence of phytophagous mites, raspberry leaf blotch disorder and raspberry leaf blotch virus (RLBV). Four sites in south-eastern Norway were sampled five times. Floricanes from different parts of the sites were collected, taking one leaf from each of the upper, middle, and bottom zones of the cane. Mites were extracted with a washing technique and processed for species identification and RLBV detection. Mites and leaves were tested for RLBV by reverse transcription polymerase chain reaction (RT-PCR) with virus-specific primers. Phytophagous mites, Phyllocoptes gracilis, Tetranychus urticae, and Neotetranychus rubi, and predatory mites, Anystis baccarum and Typhlodromus (Typhlodromus) pyri were identified. All phytophagous mites in cultivated raspberry preferred the upper zone of floricanes, while in non-cultivated raspberry, they preferred the middle zone. The presence of phytophagous mites did not lead to raspberry leaf blotch disorder during this study. RLBV was detected in 1.3% of the sampled plants, none of them with leaf blotch symptoms, and in 4.3% of P. gracilis samples, and in some spider mite samples, implying that Tetranychids could also be vectors of RLBV.
PubMed: 38937376
DOI: 10.1007/s10493-024-00930-7 -
Neuroscience Jun 2024The mammalian brain's complete dependence on oxygen for ATP production makes it highly susceptible to hypoxia, at high altitudes or in clinical scenarios including... (Review)
Review
The mammalian brain's complete dependence on oxygen for ATP production makes it highly susceptible to hypoxia, at high altitudes or in clinical scenarios including anemia or pulmonary disease. Hypoxia plays a crucial role in the development of various brain disorders, such as Alzheimer's, Parkinson's, and other age-related neurodegenerative diseases. On the other hand, a decrease in environmental oxygen levels, such as prolonged stays at high elevations, may have beneficial impacts on the process of ageing and the likelihood of death. Additionally, the utilization of controlled hypoxia exposure could potentially serve as a therapeutic approach for age-related brain diseases. Recent findings indicate that the involvement of HIF-1α and the NLRP3 inflammasome is of significant importance in the development of Alzheimer's disease. HIF-1α serves as a pivotal controller of various cellular reactions to oxygen deprivation, exerting influence on a multitude of physiological mechanisms such as energy metabolism and inflammatory responses. The NLRP3 plays a crucial role in the innate immune system by coordinating the initiation of inflammatory reactions through the assembly of the inflammasome complex. This review examines the information pertaining to the contrasting effects of hypoxia on the brain, highlighting both its positive and deleterious effects and molecular pathways that are involved in mediating these different effects. This study explores potential strategies for therapeutic intervention that focus on restoring cellular balance and reducing neuroinflammation, which are critical aspects in addressing this severe neurodegenerative condition and addresses crucial inquiries that warrant further future investigations.
PubMed: 38936458
DOI: 10.1016/j.neuroscience.2024.06.021