scholarly journals TMT-Based Plasma Proteomics Reveals Dyslipidemia Among Lowlanders During Prolonged Stay at High Altitudes

2021 ◽  
Vol 12 ◽  
Author(s):  
Pooja ◽  
Vandana Sharma ◽  
Ram Niwas Meena ◽  
Koushik Ray ◽  
Usha Panjwani ◽  
...  

Acute exposure to high altitude perturbs physiological parameters and induces an array of molecular changes in healthy lowlanders. However, activation of compensatory mechanisms and biological processes facilitates high altitude acclimatization. A large number of lowlanders stay at high altitude regions from weeks to months for work and professional commitments, and thus are vulnerable to altitude-associated disorders. Despite this, there is a scarcity of information for molecular changes associated with long-term stay at high altitudes. In the present study, we evaluated oxygen saturation (SpO2), heart rate (HR), and systolic and diastolic blood pressure (SBP and DBP) of lowlanders after short- (7 days, HA-D7) and long-term (3 months, HA-D150) stay at high altitudes, and used TMT-based proteomics studies to decipher plasma proteome alterations. We observed improvements in SpO2 levels after prolonged stay, while HR, SBP, and DBP remained elevated as compared with short-term stay. Plasma proteomics studies revealed higher levels of apolipoproteins APOB, APOCI, APOCIII, APOE, and APOL, and carbonic anhydrases (CA1 and CA2) during hypoxia exposure. Biological network analysis also identified profound alterations in lipoprotein-associated pathways like plasma lipoprotein assembly, VLDL clearance, chylomicron assembly, chylomicron remodeling, plasma lipoprotein clearance, and chylomicron clearance. In corroboration, lipid profiling revealed higher levels of total cholesterol (TC), triglycerides (TGs), low-density lipoprotein (LDL) for HA-D150 whereas high density lipoproteins (HDL) levels were lower as compared with HA-D7 and sea-level indicating dyslipidemia. We also observed higher levels of proinflammatory cytokines IL-6, TNFα, and CRP for HA-D150 along with oxidized LDL (oxLDL), suggesting vascular inflammation and proartherogenic propensity. These results demonstrate that long-term stay at high altitudes exacerbates dyslipidemia and associated disorders.

High altitude deterioration means a gradual diminution in man’s capacity to do work at great heights. This is associated with insomnia, lack of appetite, loss of weight and increasing lethargy. These symptoms appear after a prolonged stay above 18000 ft. and there is great individual variation. Man would deteriorate after a time at these heights even under the best con­ditions: if he is doing hard work and is subjected to many strains, mental and physical, other factors are brought to bear which will aggravate this basic state. Such factors are illness, exhaustion, starvation and dehydration. Symptoms similar to those of deterioration, but more acute in onset, appear if man goes too quickly to high altitudes without first acclimatizing. These symptoms of acute mountain sickness disappear if the subject returns to lower levels for some time. If he goes to moderate heights when acclimatizing he will be able to stay for reasonably long periods without undue trouble. Exhaustion at high altitudes is often only cured by coming down to lower levels, as above a certain height there seems to be little or no recovery.


Author(s):  
Dean Jacobsen ◽  
Olivier Dangles

Chapter 2 presents the amazing variety of running waters, lakes, ponds, and wetlands found at high altitudes. These waterbodies are not equally distributed among the world’s high altitude places, but tend to be concentrated in certain areas, primarily determined by regional climate and topography. Thus, a large proportion of the world’s truly high altitude aquatic systems are found at lower latitudes, mostly in the tropics. The chapter presents general patterns in the geographical distribution of high altitude waters, and gives examples of some of the most extreme systems. High altitude aquatic systems and habitats cover a broad variety in dynamics and physical appearance. These differences may be related to, for example, water source (glacier-fed, rain-fed, or groundwater-fed streams), geological origin (e.g. glacial, volcanic, or tectonic lakes), or catchment slope and altitude (different types of peatland wetlands). This is exemplified and richly illustrated through numerous photos.


2021 ◽  
Vol 9 (1) ◽  
Author(s):  
Isabel Jiménez ◽  
Bárbara Tazón-Vega ◽  
Pau Abrisqueta ◽  
Juan C. Nieto ◽  
Sabela Bobillo ◽  
...  

Abstract Background Mechanisms driving the progression of chronic lymphocytic leukemia (CLL) from its early stages are not fully understood. The acquisition of molecular changes at the time of progression has been observed in a small fraction of patients, suggesting that CLL progression is not mainly driven by dynamic clonal evolution. In order to shed light on mechanisms that lead to CLL progression, we investigated longitudinal changes in both the genetic and immunological scenarios. Methods We performed genetic and immunological longitudinal analysis using paired primary samples from untreated CLL patients that underwent clinical progression (sampling at diagnosis and progression) and from patients with stable disease (sampling at diagnosis and at long-term asymptomatic follow-up). Results Molecular analysis showed limited and non-recurrent molecular changes at progression, indicating that clonal evolution is not the main driver of clinical progression. Our analysis of the immune kinetics found an increasingly dysfunctional CD8+ T cell compartment in progressing patients that was not observed in those patients that remained asymptomatic. Specifically, terminally exhausted effector CD8+ T cells (T-betdim/−EomeshiPD1hi) accumulated, while the the co-expression of inhibitory receptors (PD1, CD244 and CD160) increased, along with an altered gene expression profile in T cells only in those patients that progressed. In addition, malignant cells from patients at clinical progression showed enhanced capacity to induce exhaustion-related markers in CD8+ T cells ex vivo mainly through a mechanism dependent on soluble factors including IL-10. Conclusions Altogether, we demonstrate that the interaction with the immune microenvironment plays a key role in clinical progression in CLL, thereby providing a rationale for the use of early immunotherapeutic intervention.


2019 ◽  
Vol 490 (1) ◽  
pp. 1397-1405 ◽  
Author(s):  
R Avila ◽  
O Valdés-Hernández ◽  
L J Sánchez ◽  
I Cruz-González ◽  
J L Avilés ◽  
...  

ABSTRACT We present optical turbulence profiles obtained with a Generalized SCIDAR (G-SCIDAR) and a low-layer SCIDAR (LOLAS) at the Observatorio Astronómico Nacional in San Pedro Mártir (OAN-SPM), Baja California, Mexico, during three observing campaigns in 2013, 2014, and 2015. The G-SCIDAR delivers profiles with moderate altitude-resolution (a few hundred metres) along the entire turbulent section of the atmosphere, while the LOLAS gives high altitude resolution (on the order of tens of metres) but only within the first few hundred metres. Simultaneous measurements were obtained on 2014 and allowed us to characterize in detail the combined effect of the local orography and wind direction on the turbulence distribution close to the ground. At the beginning of several nights, the LOLAS profiles show that turbulence peaks between 25 and 50 m above the ground, not at ground level as was expected. The G-SCIDAR profiles exhibit a peak within the first kilometre. In 55 per cent and 36 per cent of the nights stable layers are detected between 10 and 15 km and at 3 km, respectively. This distribution is consistent with the results obtained with a G-SCIDAR in 1997 and 2000 observing campaigns. Statistics computed with the 7891 profiles that have been measured at the OAN-SPM with a G-SCIDAR in 1997, 2000, 2014, and 2015 campaigns are presented. The seeing values calculated with each of those profiles have a median of 0.79, first and third quartiles of 0.51 and 1.08 arcsec, which are in close agreement with other long term seeing monitoring performed at the OAN-SPM.


2021 ◽  
Vol 11 (4) ◽  
pp. 435
Author(s):  
Andreas-Christian Hade ◽  
Mari-Anne Philips ◽  
Ene Reimann ◽  
Toomas Jagomäe ◽  
Kattri-Liis Eskla ◽  
...  

The Mediodorsal (MD) thalamus that represents a fundamental subcortical relay has been underrepresented in the studies focusing on the molecular changes in the brains of subjects with alcohol use disorder (AUD). In the current study, MD thalamic regions from AUD subjects and controls were analyzed with Affymetrix Clariom S human microarray. Long-term alcohol use induced a significant (FDR ≤ 0.05) upregulation of 2802 transcripts and downregulation of 1893 genes in the MD thalamus of AUD subjects. A significant upregulation of GRIN1 (glutamate receptor NMDA type 1) and FTO (alpha-ketoglutarate dependent dioxygenase) was confirmed in western blot analysis. Immunohistochemical staining revealed similar heterogenous distribution of GRIN1 in the thalamic nuclei of both AUD and control subjects. The most prevalent functional categories of upregulated genes were related to glutamatergic and GABAergic neurotransmission, cellular metabolism, and neurodevelopment. The prevalent gene cluster among down-regulated genes was immune system mediators. Forty-two differentially expressed genes, including FTO, ADH1B, DRD2, CADM2, TCF4, GCKR, DPP6, MAPT and CHRH1, have been shown to have strong associations (FDR p < 10−8) with AUD or/and alcohol use phenotypes in recent GWA studies. Despite a small number of subjects, we were able to detect robust molecular changes in the mediodorsal thalamus caused by alcohol emphasizing the importance of deeper brain structures such as diencephalon, in the development of AUD-related dysregulation of neurocircuitry.


2021 ◽  
Vol 12 ◽  
Author(s):  
Yu Jinqiu ◽  
Li Bing ◽  
Song Tingting ◽  
He Jinglei ◽  
KongLing Zelai ◽  
...  

Oat is an annual gramineous forage grass with the remarkable ability to survive under various stressful environments. However, understanding the effects of high altitude stresses on oats is poor. Therefore, the physiological and the transcriptomic changes were analyzed at two sites with different altitudes, low (ca. 2,080 m) or high (ca. 2,918 m), respectively. Higher levels of antioxidant enzyme activity, reactive oxygen and major reductions in photosynthesis-related markers were suggested for oats at high altitudes. Furthermore, oat yields were severely suppressed at the high altitude. RNA-seq results showed that 11,639 differentially expressed genes were detected at both the low and the high altitudes in which 5,203 up-regulated and 6,436 down-regulated. Gene Ontology and Kyoto Encyclopedia of Genes and Genomes pathway enrichment tests were conducted and a group of major high altitude-responsive pigment metabolism genes, photosynthesis, hormone signaling, and cutin, suberine and wax biosynthesis were excavated. Using quantitative real-time polymerase chain response, we also confirmed expression levels of 20 DEGs (qRT-PCR). In summary, our study generated genome-wide transcript profile and may be useful for understanding the molecular mechanisms of Avena sativa L. in response to high altitude stress. These new findings contribute to our deeper relevant researches on high altitude stresses and further exploring new candidategenes for adapting plateau environment oat molecular breeding.


2020 ◽  
Author(s):  
Jamal Omar ◽  
Nidal Jaradat ◽  
Mohammad Qadoumi ◽  
Abdel Naser Qadoumi

Abstract Background: Swimming and other aquatic fitness are important aerobic exercises that have been proposed as an effective nonpharmacological approach in the management of type 2 diabetes (T2DM), hyperlipidemia, and hypertension (HTN). The current study aimed to assess the effect of long-term swimming sessions on glycemic and lipidemic parameters, body composition, and hemodynamic responses for patients with metabolic risk factors. Methods: Forty participants from both genders with T2DM and HTN (aged 52.4±5.5 yrs) agreed to take part in this quasi-experimental study and were divided into two groups. The first group included the participants who performed long-term swimming sessions and the second group served as the reference. The first group exercised for 2 h, 3 times/week in 29-33 ◦C swimming pool for 16 weeks. While the reference group did not participate in any kind of exercise and advised to keep on with their normal lifestyle. All the obtained metabolic syndrome risk factors data were analyzed using a paired t-test which was applied to separately determine the differences between pre- and post-tests for both genders and groups, and the percentage of change (Δ %) was computed. Independent t-test was applied to determine the differences in the post-tests (Exp. vs Ref) in men patients as well as for women separately. Results: The results showed that there were statistically significant differences at p ≤ 0.05 between pre- and post- exercise concerning Total Cholesterol (TC), High-Density Lipoproteins (HDL), Low-Density Lipoproteins (LDL), Triglycerides (TG), glycemic parameters, systolic and diastolic blood pressures, body mass index (BMI) and fat mass percent in favor of posttests in the experimental group for both genders. Whereas, no significant differences were found at p≤0.05 between pre- and post-tests for all studied variables in the reference group for both genders. Significant differences were found at p≤0.05 on the post-tests in favor of the experimental for both genders.Conclusion: Findings of the current study suggested that the regular 16 weeks of the conducted swimming sessions could be considered as nonpharmacological approaches in the management of T2DM and HTN.


2021 ◽  
Vol 12 ◽  
Author(s):  
Ivan Lopez ◽  
Reinaldo Aravena ◽  
Daniel Soza ◽  
Alicia Morales ◽  
Silvia Riquelme ◽  
...  

The Chilean workforce has over 200,000 people that are intermittently exposed to altitudes over 4,000 m. In 2012, the Ministry of Health provided a technical guide for high-altitude workers that included a series of actions to mitigate the effects of hypoxia. Previous studies have shown the positive effect of oxygen enrichment at high altitudes. The Atacama Large Millimeter/submillimeter Array (ALMA) radiotelescope operates at 5,050 m [Array Operations Site (AOS)] and is the only place in the world where pressure swing adsorption (PSA) and liquid oxygen technologies have been installed at a large scale. These technologies reduce the equivalent altitude by increasing oxygen availability. This study aims to perform a retrospective comparison between the use of both technologies during operation in ALMA at 5,050 m. In each condition, variables such as oxygen (O2), temperature, and humidity were continuously recorded in each AOS rooms, and cardiorespiratory variables were registered. In addition, we compared portable O2 by using continuous or demand flow during outdoor activities at very high altitudes. The outcomes showed no differences between production procedures (PSA or liquid oxygen) in regulating oxygen availability at AOS facilities. As a result, big-scale installations have difficulties reaching the appropriate O2 concentration due to leaks in high mobility areas. In addition, the PSA plant requires adequacy and maintenance to operate at a very high altitude. A continuous flow of 2–3 l/min of portable O2 is recommended at 5,050 m.


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