Comparing high versus low-altitude populations to test human adaptations for increased ventilation during sustained aerobic activity.
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ABSTRACT:
SUBMITTER: Callison WE
PROVIDER: S-EPMC9249887 | biostudies-literature |
REPOSITORIES: biostudies-literature
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Project description:Admixture is recognized as a widespread feature of human populations, renewing interest in the possibility that genetic exchange can facilitate adaptations to new environments. Studies of Tibetans revealed candidates for high-altitude adaptations in the EGLN1 and EPAS1 genes, associated with lower haemoglobin concentration. However, the history of these variants or that of Tibetans remains poorly understood. Here we analyse genotype data for the Nepalese Sherpa, and find that Tibetans are a mixture of ancestral populations related to the Sherpa and Han Chinese. EGLN1 and EPAS1 genes show a striking enrichment of high-altitude ancestry in the Tibetan genome, indicating that migrants from low altitude acquired adaptive alleles from the highlanders. Accordingly, the Sherpa and Tibetans share adaptive haemoglobin traits. This admixture-mediated adaptation shares important features with adaptive introgression. Therefore, we identify a novel mechanism, beyond selection on new mutations or on standing variation, through which populations can adapt to local environments.
| S-EPMC4643256 | biostudies-literature
Project description:Although hypoxia is a major stress on physiological processes, several human populations have survived for millennia at high altitudes, suggesting that they have adapted to hypoxic conditions. This hypothesis was recently corroborated by studies of Tibetan highlanders, which showed that polymorphisms in candidate genes show signatures of natural selection as well as well-replicated association signals for variation in hemoglobin levels. We extended genomic analysis to two Ethiopian ethnic groups: Amhara and Oromo. For each ethnic group, we sampled low and high altitude residents, thus allowing genetic and phenotypic comparisons across altitudes and across ethnic groups. Genome-wide SNP genotype data were collected in these samples by using Illumina arrays. We find that variants associated with hemoglobin variation among Tibetans or other variants at the same loci do not influence the trait in Ethiopians. However, in the Amhara, SNP rs10803083 is associated with hemoglobin levels at genome-wide levels of significance. No significant genotype association was observed for oxygen saturation levels in either ethnic group. Approaches based on allele frequency divergence did not detect outliers in candidate hypoxia genes, but the most differentiated variants between high- and lowlanders have a clear role in pathogen defense. Interestingly, a significant excess of allele frequency divergence was consistently detected for genes involved in cell cycle control and DNA damage and repair, thus pointing to new pathways for high altitude adaptations. Finally, a comparison of CpG methylation levels between high- and lowlanders found several significant signals at individual genes in the Oromo.
| S-EPMC3516565 | biostudies-literature
Project description:BackgroundMindfulness Based Stress Reduction (MBSR) is a secular form of meditation training. The vast majority of the extant literature investigating the health effects of mindfulness interventions relies on wait-list control comparisons. Previous studies have found that meditation training over several months is associated with improvements in cognitive control and attention.Methodology/principal findingsWe used a visual continuous performance task (CPT) to test the effects of eight weeks of mindfulness training on sustained attention by comparing MBSR to the Health Enhancement Program (HEP), a structurally equivalent, active control condition in a randomized, longitudinal design (ClinicalTrials.gov, NCT01301105) focusing on a non-clinical population typical of MBSR participants. Researchers were blind to group assignment. 63 community participants were randomized to either MBSR (n?=?31) or HEP (n?=?32). CPT analyses were conducted on 29 MBSR participants and 25 HEP participants. We predicted that MBSR would improve visual discrimination ability and sustained attention over time on the CPT compared to HEP, with more home practice associated with greater improvements. Our hypotheses were not confirmed but we did find some evidence for improved visual discrimination similar to effects in partial replication of other research. Our study had sufficient power to demonstrate that intervention groups do not differ in their improvement over time in sustained attention performance. One of our primary predictions concerning the effects of intervention on attentional fatigue was significant but not interpretable.ConclusionsAttentional sensitivity is not affected by mindfulness practice as taught in MBSR, but it is unclear whether mindfulness might positively affect another aspect of attention, vigilance. These results also highlight the relevant procedural modifications required by future research to correctly investigate the role of sustained attention in similar samples.Trial registrationClinicalTrials.gov, NCT01301105.
| S-EPMC4067292 | biostudies-literature
Project description:Mountain plants, challenged by vegetation time contractions and dynamic changes in environmental conditions, developed adaptations that help them to balance their growth, reproduction, survival, and regeneration. However, knowledge regarding the genetic basis of species adaptation to higher altitudes remain scarce for most plant species. Here, we attempted to identify such corresponding genomic regions of high evolutionary importance in two closely related European pines, Pinus mugo and P. uncinata, contrasting them with a reference lowland relative-P. sylvestris. We genotyped 438 samples at thousands of single nucleotide polymorphism (SNP) markers, tested their genetic differentiation and population structure followed by outlier detection and gene ontology annotations. Markers clearly differentiated the species and uncovered patterns of population structure in two of them. In P. uncinata three Pyrenean sites were grouped together, while two outlying populations constituted a separate cluster. In P. sylvestris, Spanish population appeared distinct from the remaining four European sites. Between mountain pines and the reference species, 35 candidate genes for altitude-dependent selection were identified, including such encoding proteins responsible for photosynthesis, photorespiration and cell redox homeostasis, regulation of transcription, and mRNA processing. In comparison between two mountain pines, 75 outlier SNPs were found in proteins involved mainly in the gene expression and metabolism.
| S-EPMC8036860 | biostudies-literature
Project description:STUDY OBJECTIVES:To validate the Sustained Attention to Response Task (SART) as a treatment effect measure in narcolepsy, and to compare the SART with the Maintenance of Wakefulness Test (MWT) and the Epworth Sleepiness Scale (ESS). DESIGN:Validation of treatment effect measurements within a randomized controlled trial (RCT). PATIENTS:Ninety-five patients with narcolepsy with or without cataplexy. INTERVENTIONS:The RCT comprised a double-blind, parallel-group, multicenter trial comparing the effects of 8-w treatments with pitolisant (BF2.649), modafinil, or placebo (NCT01067222). MWT, ESS, and SART were administered at baseline and after an 8-w treatment period. The severity of excessive daytime sleepiness and cataplexy was also assessed using the Clinical Global Impression scale (CGI-C). MEASUREMENTS AND RESULTS:The SART, MWT, and ESS all had good reliability, obtained for the SART and MWT using two to three sessions in 1 day. The ability to distinguish responders from nonresponders, classified using the CGI-C score, was high for all measures, with a high performance for the SART (r = 0.61) and the ESS (r = 0.54). CONCLUSIONS:The Sustained Attention to Response Task is a valid and easy-to-administer measure to assess treatment effects in narcolepsy, enhanced by combining it with the Epworth Sleepiness Scale.
| S-EPMC4481014 | biostudies-literature
Project description:Central and eastern chimpanzees are infected with Simian Immunodeficiency Virus (SIV) in the wild, typically without developing acute immunodeficiency. Yet the recent zoonotic transmission of chimpanzee SIV to humans, which were naïve to the virus, gave rise to the Human Immunodeficiency Virus (HIV), which causes AIDS and is responsible for one of the deadliest pandemics in human history. Chimpanzees have likely been infected with SIV for tens of thousands of years and have likely evolved to reduce its pathogenicity, becoming semi-natural hosts that largely tolerate the virus. In support of this view, central and eastern chimpanzees show evidence of positive selection in genes involved in SIV/HIV cell entry and immune response to SIV, respectively. We hypothesise that the population first infected by SIV would have experienced the strongest selective pressure to control the lethal potential of zoonotic SIV, and that population genetics will reveal those first critical adaptations. With that aim we used population genetics to investigate signatures of positive selection in the common ancestor of central-eastern chimpanzees. The genes with signatures of positive selection in the ancestral population are significantly enriched in SIV-related genes, especially those involved in the immune response to SIV and those encoding for host genes that physically interact with SIV/HIV (VIPs). This supports a scenario where SIV first infected the central-eastern ancestor and where this population was under strong pressure to adapt to zoonotic SIV. Interestingly, integrating these genes with candidates of positive selection in the two infected subspecies reveals novel patterns of adaptation to SIV. Specifically, we observe evidence of positive selection in numerous steps of the biological pathway responsible for T-helper cell differentiation, including CD4 and multiple genes that SIV/HIV use to infect and control host cells. This pathway is active only in CD4+ cells which SIV/HIV infects, and it plays a crucial role in shaping the immune response so it can efficiently control the virus. Our results confirm the importance of SIV as a selective factor, identify specific genetic changes that may have allowed our closest living relatives to reduce SIV's pathogenicity, and demonstrate the potential of population genomics to reveal the evolutionary mechanisms used by naïve hosts to reduce the pathogenicity of zoonotic pathogens.
| S-EPMC9467346 | biostudies-literature
Project description:Through the use of proteomic analysis of 32 dental calculus samples from anceint Mongolia, we show that ruminant dairying was present in Mongolia by at least 3000 B.C.E., over 1500 years prior to previously published work. Excitingly, the earliest site with dairy evidence has been identified as archaeologically Afanasievo, supporting the hypothesis that dairy practices and animals likely entered the Eastern steppe with migrating western steppe populations. Furthermore, at 1200 B.C.E. we detect the first direct evidence for horse milk consumption, demonstrating the Bronze Age origins of equine dairying on the eastern steppe which occurred concomitantly with early evidence for horse bridling and riding in the region. The incorporation of horse milk and riding into early Mongolian subsistence strategies led to dramatic economic and demographic shifts that enabled the formation of the well-known steppe empires.
2020-03-05 | PXD014730 | Pride
Project description:ObjectiveThe 10 m modified shuttle walking test (MSWT) is recommended to determine the functional capacity in older individuals and for patients entering cardiac rehabilitation. Participants are required to negotiate around cones set 1 m from the end markers. However, consistent comments indicate that for some individuals manoeuvring around the cones can be quite difficult. Therefore, the objective of this study was to explore differences within and between non-cardiac and postmyocardial infarction (MI) males during MSWT with and without the cones.DesignComparative study.Participants20 post-MI (64.8±6.6, range 51-74 years) and 20 non-cardiac male controls (64.1±5.7, range 52-74 years) participated.MethodsParticipants performed MSWT with and without cones. Throughout, the participants expired air, and the heart rate (bpm) (HR) and ratings of perceived exertion (RPE) were measured. Participant protocol preference was recorded verbatim.ResultsOne-way analysis of variance found no significant difference in VO2 peak (cones 20.4±5.1 vs no-cones 21.9±4.8 ml/kg/min, p=0.197) or distance ambulated (cones 631.8±132.9 m vs no-cones 662.4±164.1 m, p=0.371) between protocols or groups. Analysis comparing lines of regression showed a significant trajectory difference in VO2 (ml/kg/min) (p<0.01) between protocols with higher HR (p<0.01) and respiratory exchange ratio (RER, p<0.001) values during cones. RPEs were higher for post-MIs versus controls during both protocols (p<0.05). Post-MIs taking ?-blockers produce significantly lower HR values. The ?(2) analysis found no significant difference in protocol preference (no-cones: all n=25, 63%; post-MIs n=13, 65%; and controls n=12, 60%).ConclusionsPost-MIs found both protocols subjectively harder than controls with no significant difference in the VO2 peak. However, both groups worked at a lesser percentage of their anaerobic threshold during no-cones protocol as indicated by lower RER values. Importantly, for the post-MIs, this would reduce their risk of functional impairment. Therefore, though more research is required, indicators at present are more favourable for the use of the no-cones with post-MIs.
| S-EPMC3664357 | biostudies-literature
Project description:Metformin and exercise independently improve insulin sensitivity and decrease the risk of diabetes. Metformin was also recently proposed as a potential therapy to slow aging. However, recent evidence indicates that adding metformin to exercise antagonizes the exercise-induced improvement in insulin sensitivity and cardiorespiratory fitness. The purpose of this study was to test the hypothesis that metformin diminishes the improvement in insulin sensitivity and cardiorespiratory fitness after aerobic exercise training (AET) by inhibiting skeletal muscle mitochondrial respiration and protein synthesis in older adults (62 ± 1 years). In a double-blinded fashion, participants were randomized to placebo (n = 26) or metformin (n = 27) treatment during 12 weeks of AET. Independent of treatment, AET decreased fat mass, HbA1c, fasting plasma insulin, 24-hr ambulant mean glucose, and glycemic variability. However, metformin attenuated the increase in whole-body insulin sensitivity and VO2 max after AET. In the metformin group, there was no overall change in whole-body insulin sensitivity after AET due to positive and negative responders. Metformin also abrogated the exercise-mediated increase in skeletal muscle mitochondrial respiration. The change in whole-body insulin sensitivity was correlated to the change in mitochondrial respiration. Mitochondrial protein synthesis rates assessed during AET were not different between treatments. The influence of metformin on AET-induced improvements in physiological function was highly variable and associated with the effect of metformin on the mitochondria. These data suggest that prior to prescribing metformin to slow aging, additional studies are needed to understand the mechanisms that elicit positive and negative responses to metformin with and without exercise.
| S-EPMC6351883 | biostudies-literature
Project description:We have surveyed 15 high-altitude adaptation candidate genes for signals of positive selection in North Caucasian highlanders using targeted re-sequencing. A total of 49 unrelated Daghestani from three ethnic groups (Avars, Kubachians, and Laks) living in ancient villages located at around 2,000 m above sea level were chosen as the study population. Caucasian (Adygei living at sea level, N = 20) and CEU (CEPH Utah residents with ancestry from northern and western Europe; N = 20) were used as controls. Candidate genes were compared with 20 putatively neutral control regions resequenced in the same individuals. The regions of interest were amplified by long-PCR, pooled according to individual, indexed by adding an eight-nucleotide tag, and sequenced using the Illumina GAII platform. 1,066 SNPs were called using false discovery and false negative thresholds of ~6%. The neutral regions provided an empirical null distribution to compare with the candidate genes for signals of selection. Two genes stood out. In Laks, a non-synonymous variant within HIF1A already known to be associated with improvement in oxygen metabolism was rediscovered, and in Kubachians a cluster of 13 SNPs located in a conserved intronic region within EGLN1 showing high population differentiation was found. These variants illustrate both the common pathways of adaptation to high altitude in different populations and features specific to the Daghestani populations, showing how even a mildly hypoxic environment can lead to genetic adaptation.
| S-EPMC3312735 | biostudies-literature