Search

Aquaporins, also known as water channels, are a large family of transmembrane channel proteins present throughout all life domains and are implicated in human disorders. The psychrophilic aquaporin comes to attention because of its specialty in adaptive ability to keep on functioning to maintain water homeostasis under low temperatures, which have an optimal temperature for growth at about 15ºC or lower. However, studies regarding aquaporin isolated from psychrophilic Pseudomonas sp. are still scattered. Recently, the genome sequence of an Antarctic Pseudomonas sp. strain AMS3 revealed a gene sequence encoding for a putative aquaporin designated as PAqpZ2_AMS3. In this study, structure analysis and molecular dynamics (MD) simulation of a predicted model of a fully hydrated aquaporin monomer was embedded in a lipid bilayer and was performed at different temperatures for structural flexibility and stability analysis. The MD simulation results revealed that the predicted structure could remain stable and flexible at low to medium temperatures. In addition, the important position of water gating amino acids, Phe36 and Asn180 residues were rearranged in -5ºC MD simulation, leading to changes in the aquaporin water column size. The information obtained from this psychrophilic aquaporin, PAqpZ2_AMS3, provides new insights into the structural adaptation of this protein at low temperatures and could be a useful tool for low-temperature industrial applications and molecular engineering purposes in the future.

Micro-organisms form the first pioneer community in the history of biological life, thought to be present in the primordial soup and evolving later with more complex life-forms. Among micro-organisms, viruses form a separate taxon of organisms. Viruses are obligate parasites, being inactive without a host and becoming active once in contact with specific hosts. Viruses, with an inherent ability to infect and hijack cellular structures, have been utilised as vectors to introduce foreign genetic material in a variety of biological species, e.g. adenoviral vectors. However, viruses have also been the root cause of many infectious diseases, most notable being HIV-AIDS, for its resistance to treatment and omnipresent occurrence. There are many families of viruses like retroviridae, picornaviridae and poxviridae. This review focuses on a specific member of the coronaviridae, the SARS-CoV-2. This virus is responsible for the current COVID-19 pandemic. This review summarises its transmission, molecular mechanism by which it causes disease, associated clinical symptoms and the strategies available to control it from sources like PubMed, Google Scholar, webservers of National Institute of Health (NIH), European Molecular Biology Laboratory (EMBL), World Health Organisation (WHO), United States Food and Drug Administration (USFDA) and Centers for Disease Control and Prevention (CDC) available as on 1st May 2021.

Extended exposure to low pO2 has multiple effects on signaling cascades. Despite multiple exploratory studies, omics studies elucidating the signaling cascades essential for surviving extended low pO2 exposures are lacking. In this study, we simulated low pO2 (PB = 40 kPa; 7620 m) exposure in male Sprague–Dawley rats for 3, 7 and 14 days. Redox stress assays and proteomics based network biology were performed using lungs and plasma. We observed that redox homeostasis was achieved after day 3 of exposure. We investigated the causative events for this. Proteo-bioinformatics analysis revealed STAT3 to be upstream of lung cytoskeletal processes and systemic lipid metabolism (RXR) derived inflammatory processes, which were the key events. Thus, during prolonged low pO2 exposure, particularly those involving slowly decreasing pressures, redox homeostasis is achieved but energy metabolism is perturbed and this leads to an immune/inflammatory signaling impetus after third day of exposure. We found that an interplay of lung cytoskeletal elements, systemic energy metabolism and inflammatory proteins aid in achieving redox homeostasis and surviving extended low pO2 exposures. Qualitative perturbations to cytoskeletal stability and innate immunity/inflammation were also observed during extended low pO2 exposure in humans exposed to 14,000 ft for 7, 14 and 21 days.

Hypoxia, particularly hypobaric hypoxia, is a multifaceted entity which includes certain molecular, patho-physiological and biochemical aspects. Any single aspect in itself cannot help us elucidate hypobaric hypoxia in its entirety. We observed three crucial lacunae within the existing literature. These include a lack of high-throughput investigations into redox PTMs, particularly NO-based PTMs; a prophylactic supplement with proven efficacy and safety which doesn’t involve medical supervision and is not contraindicated in hepatic, renal and cardiac insufficiencies; and a clinically validated rodent model of HAPE without any genetic/pharmacological manipulations. In the present study, we present an antagonistic interplay between nitrosylation and carbonylation which shows an additional NO-based network that is active in acclimatised individuals. Then we present a micronised aqueous suspension of silymarin which is efficacious at low doses in providing antioxidant, anti-inflammatory and hypoxia-adaptive vascular responses in addition to being a free radical quencher itself. Silymarin has an excellent safety and efficacy profile in humans. Finally, we create a SD rat model of HAPE which was used to reverse-translate a previously known HAPE marker in humans (SULT1A1) and elucidate the synergistic occurrence of HAPE and inflammation cascades. This is the first radiologically validated rodent HAPE model. In conclusion, we were able to elucidate the molecular, biochemical and patho-physiological aspects of hypobaric hypoxia which were left out by previous studies.

Hypobaric hypoxia (HH), a pathophysiological condition caused by an ascent to a high altitude. It occurs due to a deficiency of oxygen at the tissue level. Saliva is an advantageous biological sample because of easy, low cost and minimally invasive sample collection and processing. Although few reports have documented the effect of long term exposure to hypobaric hypoxia on salivary proteome but short term proteome based study remains uninvestigated. In this study, age-matched male SD rats were exposed to simulated hypobaric hypoxia (~ 25,000 ft, 7620 m) for 1 day (HD1), 3 days (HD3) and 7 days (HD7) followed by iTRAQ based LCMS/MS comparison with normoxic controls. Oxidative stress being the main event of hypobaric hypoxia suggested an initial increase in levels of oxidative stress parameters such as reactive oxygen species (ROS) and lipid peroxidation; and decrease in antioxidant enzymes such as the activity of catalase and reduced glutathione. Based on iTRAQ, out of 67 differentially expressed proteins, 36 (22 up-regulated and 14 down-regulated), 45 (24 up-regulated and 21 down-regulated), and 45 (19 up-regulated and 26 down-regulated) were modulated in HD1, HD3, and HD7 group respectively. Few proteins such as BPI fold-containing family A member 2, cystatin, and carbonic anhydrase 1 showed many folds differential expression in exposed groups as compared to normoxia. Through Ingenuity Pathways analysis, we have observed glucocorticoid receptor signaling and MSP-RON pathway to be most significantly affected. Glucocorticoid receptor signaling and MSP-RON signalling being the most significant pathways involved modulated proteins such as annexin 1, hsp90, keratin, actin-beta, and kallikrein 1. These proteins were found to aid in acclimatization and survival during hypobaric hypoxia. Taken together, this study provided the proof of concept for footprints of hypobaric hypoxia-mediated events during short term exposure through rat salivary proteome.

Hypoxia is an important feature of multiple diseases like cancer and obesity and also an environmental stressor to high altitude travelers. Emerging research suggests the importance of redox signaling in physiological responses transforming the notion of oxidative stress into eustress and distress. However, the behavior of redox protein post-translational modifications (PTMs), and their correlation with stress acclimatization in humans remains sketchy. Scant information exists about modifications in redoxome during physiological exposure to environmental hypoxia. In this study, we investigated redox PTMs, nitrosylation and carbonylation, in context of extended environmental hypoxia exposure.The volunteers were confirmed to be free of any medical conditions and matched for age and weight. The human global redoxome and the affected networks were investigated using TMT-labeled quantitative proteo-bioinformatics and biochemical assays. The percolator PSM algorithm was used for peptide-spectrum match (PSM) validation in database searches. The FDR for peptide matches was set to 0.01. 1-way ANOVA and Tukey's Multiple Comparison test were used for biochemical assays. p-value0.05 was considered statistically significant. Three independent experiments (biological replicates) were performed. Results were presented as Mean ± standard error of mean (SEM).This investigation revealed direct and indirect interplay between nitrosylation and carbonylation especially within coagulation and inflammation networks; interlinked redox signaling (via nitrosylation‑carbonylation); and novel nitrosylation and carbonylation sites in individual proteins.This study elucidates the role of redox PTMs in hypoxia signaling favoring tolerance and survival. Also, we demonstrated direct and indirect interplay between nitrosylation and carbonylation is crucial to extended hypoxia tolerance.

Hypobaric hypoxia (HH) is the hypoxia caused by decreased ambient atmospheric pressure (partial pressure of oxygen) as one ascends beyond 2500 m. The entire spectrum of molecular and biochemical studies regarding the effects of HH on an organism heavily depends on biological fluids during exposure to HH. The biological fluids are important sample types. This is because they are easiest to collect using minimally invasive collection procedures, easy to handle and store and low quantities are required for tests/assays. Although many reviews on hypobaric hypoxia in the recent past have been dedicated to the various advances made possible due to the study of biological fluids, biological fluids themselves have never been categorized according to studies done using them. This review concisely outlines the myriad results (particularly translational) in context of hypobaric hypoxia that have been observed in biological fluids, their collection strategies, storage strategies and ethical guidelines. Biological fluidscategorized here are blood (plasma and serum), saliva, tears and urine in context of research on HH and diseases like cancer where hypoxia is an essential condition. This review shall be of help to young investigators for choice of biological samples to be used in their experiments concerning hypoxia related studies and to clinicians involved in translational research providing them a ready reckoner for improving or modifying their approaches.

Exposure to high altitude above 3000 m leads to two outcomes-acclimation or high-altitude maladies. To reach a particular outcome, the plasma proteome is modified differentially, either in context of an acclimation response or mal-acclimation response leading to disease. This ensures that hypoxia-responsive plasma protein trends reflect acclimation in acclimated individuals when compared with their levels prior to acclimation. Such protein trends could be used to assess acclimation in an individual and any significant deviation from this trend may indicate non-acclimation, thereby preventing high-altitude illnesses before they manifest. In this study, we investigate and statistically evaluate the trendlines of various hypoxia-responsive plasma protein levels, reported significantly perturbed in our previous studies, in individuals (male; n = 20) exposed to 3520 m at high-altitude day 1 (HAD1), HAD4, and HAD7L and to 4420 m at HAD7H, HAD30, and HAD120. We observe that thioredoxin (Trx), glutathione peroxidase 3 (GPx-3), and apolipoprotein AI (Apo-AI) are statistically robust markers to assess acclimation across the exposure duration while sulfotransferase 1A1 (ST1A1) is a capable negative control whose levels increase only in cases of HAPE. We also observe exposure day-specific and resident altitude-specific proteins capable of accurately assessing acclimation when compared with baseline levels or the lower altitude zone.

Background: Hypoxia is a pathophysiological condition which arises due to low oxygen concentration in conditions like cardiovascular diseases, inflammation, ascent to higher altitude, malignancies, deep sea diving, prenatal birth, etc. A number of microRNAs (miRNAs), Transcription Factors (TFs) and genes have been studied separately for their role in hypoxic adaptation and controlling cell-cycle progression and apoptosis during this stress. Objective: We hypothesize that miRNAs and TFs may act in conjunction to regulate a multitude of genes and play a crucial and combinatorial role during hypoxia-stress-responses and associated cellcycle control mechanisms. Method: We collected a comprehensive and non-redundant list of human hypoxia-responsive miRNAs (also known as hypoxiamiRs). Their experimentally validated gene-targets were retrieved from various databases and a comprehensive hypoxiamiR-gene regulatory network was built. Results: Functional characterization and pathway enrichment of genes identified phospho-proteins as enriched nodes. The phospho-proteins which were localized both in the nucleus and cytoplasm and could potentially play important role as signaling molecules were selected; and further pathway enrichment revealed that most of them were involved in NFkB signaling. Topological analysis identified several critical hypoxiamiRs and network perturbations confirmed their importance in the network. Feed Forward Loops (FFLs) were identified in the subnetwork of enriched genes, miRNAs and TFs. Statistically significant FFLs consisted of four miRNAs (hsa-miR-182-5p, hsa- miR-146b-5p, hsa-miR-96, hsa-miR-20a) and three TFs (SMAD4, FOXO1, HIF1A) both regulating two genes (NFkB1A and CDKN1A). Conclusion: Detailed BioCarta pathway analysis identified that these miRNAs and TFs together play a critical and combinatorial role in regulating cell-cycle under hypoxia, by controlling mechanisms that activate cell-cycle checkpoint protein, CDKN1A. These modules work synergistically to regulate cell-proliferation, cell-growth, cell-differentiation and apoptosis during hypoxia. A detailed mechanistic molecular model of how these co-regulatory FFLs may regulate the cell-cycle transitions during hypoxic stress conditions is also put forth. These biomolecules may play a crucial and deterministic role in deciding the fate of the cell under hypoxic-stress.

Extended exposure to low pO

In the ongoing COVID-19 pandemic, the global fraternity of researchers has been assiduously investigating pharmacological interventions against the SARS-CoV2. This novel virus is known to gain entry through the ACE 2 receptor of pulmonary epithelial cells lining the respiratory tract. Many of its initial symptoms (e.g. difficulty breathing) resemble acute high altitude illnesses, particularly HAPE. Based on these overt symptoms, a number of high altitude researchers have speculated on repurposing of drugs used to treat acute altitude illnesses (especially HAPE). However, eminent high altitude researchers with medical expertise as well as some studies on the deeper causes underlying the overt symptoms have found that such repurposing maybe counter-productive. Other factors, (e.g. contra-indications of these drugs), make their use in COVID-19 patients hazardous. The fit-for-repurposing options maybe experimental prophylactic interventions (e.g. silymarin, curcumin) which have proven anti-oxidant and anti-inflammatory effects. Another line of thought focuses on proteomics-based investigations of such patients. However, apart from the logistical and safety issues, a targeted proteomics approach based on prior sound molecular investigations is a more logical approach instead of mere shotgun proteomics. In this commentary, we shed light on such issues associated with COVID-19.

Hyper sexuality is not a new phenomenon of social deviant. This problem is even more serious when there are many apps and social media facilities with a variety of functions and features that allowed users to engage in online sexual activity. This misbehaviour causes users to experience excessive sexual addiction that leads to hyper cyber sexual problems. Various studies on hyper sexuality have been conducted by scholars that included a variety of respondents’ backgrounds. Similarly, various measurements have been developed to determine hypersexual levels. But as far as it fits in with the social media context, it remains questionable since hyper cyber sexual terminology has not been widely explored. Thus, this systematic review will be examining the measurement of online hypersexual that have been developed by scholars in the context of social media. The results showed that there were four studies have been developed on online hypersexual measurements. It is important to contextualize the findings that the needs to develop the comprehensive instrument related to hyper cyber sexual are crucial due to the increase of online sexual crimes that will be harming the values and social norm of the society.

In the new era of technology, an increasing number of people are starting to use the internet and at the same time, online gaming or online video games have become extremely popular among the young generation of youths, especially students. Online gaming will give the youths or students an escape from reality and most of them will get an addictive, adrenaline rush when they are facing a new challenge in a game. Online gaming addiction is still a mysterious problem in social life and people find it hard to regulate their time spent online and this situation even develops symptoms of compulsive online gaming players. The researcher referred to two theories, which are Uses and Gratification Theory (UGT) and Theory of Planned Behavior (TPB) to conduct the three main factors (independent variables), which are social factors, psychological factors, and media factors. Therefore, this research study is to investigate the factors students addicted to online gaming or online video games among university students. This qualitative research has involved 100 respondents and the questionnaire was distributed by using a Google Form to the targeted respondents. The respondents were among Universiti Utara Malaysia (UUM) specifically the College of Business Faculty-student who were randomly selected. The results show that social factors, psychological factors, and media factors have been contributed to online gaming addiction among university students. The online gaming addiction among College of Business Faculty-student was moderate and not too addictive. Hopefully, this research also can suit as a reference to be used for various people such as parents, educators, school administers, researchers and the society to provide strategic and initiative guidance in playing online gaming.

Health literacy (HL) is an essential component of various literacies mentioned in the field of health and education, including cultural, technological, media and scientific literacies. It is important for motivating higher consumer engagement. Health literacy (HL) describes an intermediate outcome of health education and health promotion and refers to an individual’s capacities, skills and motivation to make judgments and decisions in everyday life concerning healthcare, disease prevention and health promotion. The aim of this study was to systematically review the literature on health literacy and health outcomes as an evidence-based review of plausible causal pathways that could best explain well-established associations between limited health literacy and health outcomes globally. This research is based on past researches by employing the systematic review approach. 8 out of 825 articles has been identified for analytical purposes in tandem with the observed theme ; the influence of health literacy on health outcomes.

Drug abuse among primary school students is a serious problem and escalating number of cases by year demands a highly effective prevention strategy. This study aimed to emphasize the prevention method by developing the ACE-Mind module using coping skills based on Cognitive Behavioral Therapy approach (CBT). This involved the use of Nowicki - Strickland Locus of Control, Coppersmith Self Esteem Inventory, The Child and Youth Resilience Measure (CYRM) and The Muslim Religiosity - Personality Inventory (MRPI). Data was analyzed using Statistical Package for Social Sciences (SPSS) version 25. The sample used in this study consist of students with low scores in four domains namely locus of control, self-esteem, resilience and religion. Descriptive and inferential statistics were used to analyze the data. The results have shown that the ACE-Mind Module successfully increases the locus of control, self-esteem, resilience and religion among the student at risk.

Protective factors are the features within the person or circumstances within the family, school or community that aid someone to handle life challenges successfully. This conceptual paper will focus on the roles of several protective factors which are locus of control, self-esteem, resilience, and religion towards the intention of drug use among young people. Referring to the proposed model, the following hypotheses have been formulated, that there are significant relationships between protective factors and the reduced intention of drug use, locus of control, self-esteem, resilience, as well as religion factor will all positively influence reduced intention of drug use. A quantitative approach will be undertaken, which is a survey. In the context of this study, the population will be group of young people who are in primary or secondary schools.

This paper seeks to pinpoint the important concept to emphasize social entrepreneurship’s role in overcoming extant relations of exploring, identifying and solving an environmental problem. It builds on the premise that social entrepreneurship not only gain a profit but also create a social value to solve an environmental problem. The development of social entrepreneurship initiative and building on theory and practice of social entrepreneurship studies, the paper complement the lack of research work relating the social entrepreneurship phenomenon by proposing a conceptual framework, which encompasses the social entrepreneurship initiatives development process, the contextual aspects and social value. The paper then provides a theoretical framework of social entrepreneurship initiatives development. The theoretical framework of social entrepreneurship and relates to environmental sustainability research. Social innovation by a social entrepreneurship to environmental sustainability, each innovation a different take on what might comprise the environmental problem or oppressive potential of social entrepreneurship. As the innovation aspect of social entrepreneurship has attracted increasing attention among social entrepreneurship researchers, the paper formulates a tentative framework for furthering views on the environmental sustainability aspects of social entrepreneurship as a positive phenomenon in attention research.

In their responses to the COVID-19 crisis, many development co-operation actors reallocated budgets and pledged new funding to support developing countries. This chapter provides preliminary estimates of funds allocated and discusses the outlook for funding in 2021 and beyond. It argues for better tracking and more transparency to make the most of increasingly limited resources.

Apo-A1 is correlated with conditions like hyperlipidemia, cardiovascular diseases, high altitude pulmonary edema and etc. where hypoxia constitutes an important facet.Hypoxia causes oxidative stress, vaso-destructive and inflammatory outcomes.Apo-A1 is reported to have vasoprotective, anti-oxidative, anti-apoptotic, and anti-inflammatory effects. However, effects of Apo-A1 augmentation during hypoxia exposure are unknown.In this study, we investigated the effects of exogenously supplementing Apo-A1-mimetic peptide on SD rats during hypoxia exposure. For easing the processes of delivery, absorption and bio-availability, Apo-A1 mimetic peptide D4F was used. The rats were given 10 mg/kg BW dose (i.p.) of D4F for 7 days and then exposed to hypoxia. D4F was observed to attenuate both oxidative stress and inflammation during hypoxic exposure. D4F improved energy homeostasis during hypoxic exposure. D4F did not affect HIF-1a levels during hypoxia but increased MnSOD levels while decreasing CRP and Apo-B levels. D4F showed promise as a prophylactic against hypoxia exposure.

Objective This study explores whether the prognosis of interstitial lung disease in rheumatoid arthritis (RA-ILD) has improved over time and assesses the potential influence of drug therapy in a large multicentre UK network. Methods We analysed data from 18 UK centres on patients meeting criteria for both RA and ILD diagnosed over a 25-year period. Data included age, disease duration, outcome and cause of death. We compared all cause and respiratory mortality between RA controls and RA-ILD patients, assessing the influence of specific drugs on mortality in four quartiles based on year of diagnosis. Results A total of 290 RA-ILD patients were identified. All cause (respiratory) mortality was increased at 30% (18%) compared with controls 21% (7%) (P =0.02). Overall, prognosis improved over quartiles with median age at death rising from 63 years to 78 years (P =0.01). No effect on mortality was detected as a result of DMARD use in RA-ILD. Relative risk (RR) of death from any cause was increased among patients who had received anti-TNF therapy [2.09 (1.1–4.0)] P =0.03, while RR was lower in those treated with rituximab [0.52(0.1–2.1)] or mycophenolate [0.65 (0.2–2.0)]. Patients receiving rituximab as their first biologic had longer three (92%), five (82%) and seven year (80%) survival than those whose first biologic was an anti-TNF agent (82%, 76% and 64%, respectively) (P =0.037). Discussion This large retrospective multicentre study demonstrates survival of patients with RA-ILD has improved. This may relate to the increasing use of specific immunosuppressive and biologic agents.

Lack of zero side-effect, prescription-less prophylactics and diagnostic markers of acclimatization status lead to many suffering from high altitude illnesses. Although not fully translated to the clinical setting, many strategies and interventions are being developed that are aimed at providing an objective and tangible answer regarding the acclimatization status of an individual as well as zero side-effect prophylaxis that is cost-effective and does not require medical supervision. This short review brings together the twin problems associated with high-altitude acclimatization, i.e. acclimatization status and zero side-effect, easy-to-use prophylaxis, for the reader to comprehend as cogs of the same phenomenon. We describe current research aimed at preventing all the high-altitude illnesses by considering them an assault on redox and energy homeostasis at the molecular level. This review also entails some proteins capable of diagnosing either acclimatization or high-altitude illnesses. The future strategies based on bioinformatics and systems biology is also discussed.

Hypoxia, especially altitude associated hypoxia is known to cause severe physiological alterations and life-threatening conditions. Impaired redox balance along with oxidative stress, protein carbonylation and instigation of apoptotic events are common sub-cellular events that follow the hypoxic insult. The role of nitric oxide (NO) is very dynamic and versatile in preventing the ill effects of hypoxia vis-a-vis reacting with oxidative species and causing protein nitrosylation. Although several mechanisms of NO-mediated cytoprotection are known during hypoxic insult, limited pieces of evidence are available to support the relationship between two downstream events of oxidative stress, protein carbonylation (caused by carbonyl; CO radical) and protein nitrosylation/nitration (caused by NO/peroxynitrite; ONOO radical). In this study, we investigated an entirely new aspect of NO protection in hypoxia involving crosstalk between carbonylation and nitrosylation. Using standard NO inhibitor l-NAME and simulated hypoxic conditions in hypoxia-sensitive cell line H9c2, we evaluated the levels of radicals, cell death, mitochondrial membrane potential, levels of protein nitrosylation, protein nitration and carbonylation and glutathione content. The results were then carefully analyzed in light of NO bioavailability. Our study shows that reducing NO during hypoxia caused cell death via the increased degree of carbonylation in proteins. This provides a new aspect of NO benefits which furthers opens new possibilities to explore potential mechanisms and effects of cross-talk between nitrosylation, protein nitration and carbonylation, especially through some common antioxidant mediators such as glutathione and thioredoxin.

Hypobaric hypoxia elicits several patho-physiological manifestations, some of which are known to be lethal. Among various molecular mechanisms proposed so far, perturbation in redox state due to imbalance between radical generation and antioxidant defence is promising. These molecular events are also related to hypoxic status of cancer cells and therefore its understanding has extended clinical advantage beyond high altitude hypoxia. In present study, however, the focus was to understand and propose a model for rapid acclimatization of high altitude visitors to enhance their performance based on molecular changes. We considered using simulated hypobaric hypoxia at some established thresholds of high altitude stratification based on known physiological effects. Previous studies have focused on the temporal aspect while overlooking the effects of varying pO2 levels during exposure to hypobaric hypoxia. The pO2 levels, indicative of altitude, are crucial to redox homeostasis and can be the limiting factor during acclimatization to hypobaric hypoxia. In this study we present the effects of acute (24 h) exposure to high (3049 m; pO2: 71 kPa), very high (4573 m; pO2: 59 kPa) and extreme altitude (7620 m; pO2: 40 kPa) zones on lung and plasma using semi-quantitative redox specific transcripts and quantitative proteo-bioinformatics workflow in conjunction with redox stress assays. It was observed that direct exposure to extreme altitude caused 100% mortality, which turned into high survival rate after pre-exposure to 59 kPa, for which molecular explanation were also found. The pO2 of 59 kPa (very high altitude zone) elicits systemic energy and redox homeostatic processes by modulating the STAT3-RXR-Nrf2 trio. Finally we posit the various processes downstream of STAT3-RXR-Nrf2 and the plasma proteins that can be used to ascertain the redox status of an individual., Graphical abstract fx1, Highlights • A comparison of effects on redox and energy homeostasis between three altitude zones. • Exposure at 59 kPa (10 h) followed by normoxia (1 h) rescues homeostasis at 40 kPa. • Redox and energy homeostasis dependent on STAT-3-RXR-Nrf interplay. • Lung redox and energy homeostasis fails at 15,000 ft. • Systemic redox and energy homeostasis activated on failure of lung homeostatic mechanisms.

Intermittent hypoxia, initially associated with adverse effects of sleep apnea, has now metamorphosed into a module for improved sports performance. The regimen followed for improved sports performance is milder intermittent hypoxic training (IHT) as compared to chronic and severe intermittent hypoxia observed in sleep apnea. Although several studies have indicated the mechanism and enough data on physiological parameters altered by IH is available, proteome perturbations remain largely unknown. Altitude induced hypobaric hypoxia is known to require acclimatization as it causes systemic redox stress and inflammation in humans. In the present study, a short IHT regimen consisting of previously reported physiologically beneficial FIO2 levels of 13.5% and 12% was administered to human subjects. These subjects were then airlifted to altitude of 3500 m and their plasma proteome along with associated redox parameters were analyzed on days 4 and 7 of high altitude stay. We observed that redox stress and associated post-translational modifications, perturbed lipid metabolism and inflammatory signaling were induced by IHT exposure at Baseline. However, this caused activation of antioxidants, energy homeostasis mechanisms and anti-inflammatory responses during subsequent high-altitude exposure. Thus, we propose IHT as a beneficial non-pharmacological intervention that benefits individuals venturing to high altitude areas.

The present study aimed to develop a protocol for easy removal of β-ODAP neurotoxin by converting it into its isomer α-ODAP (reported to be less toxic) followed by its separation from the protein fraction in pH dependent manner. Use of β-mercaptoethanol prevented aggregate formation and increased solubility of the prepared Lathyrus sativus protein. Validation of ODAP removal by paper chromatography and mass spectrometry indicated the robustness of the protocol. Removal of ODAP and presence of high antioxidants and homoarginine content can enable Lathyrus sativus to be an alternate source of protein, as well as have other health benefits, including benefits for patients with cardiovascular diseases.

Aims HAPE remains the most common lethal high-altitude disease. Although its pathophysiology and other associated causal factors have been partially uncovered along with some potential biomarker proteins, it has not been completely elucidated. A major hindrance to improving the understanding of HAPE pathophysiology and associated molecular events has been the absence of a quick, reliable and definitive animal model of HAPE. This study is aimed at development of a rapid and reliable SD rat model of high altitude pulmonary edema (HAPE) that can be roentgenographically confirmed and be used to study protein markers of HAPE. Main methods In this study, we detail the process of rapidly inducing HAPE in male SD rats within 18 h of simulated high-altitude exposure without causing high rates of mortality. Thereafter, we confirmed HAPE using roentgenography. We assessed Sulfotransferase 1A1 (SULT1A1), IL-1 beta, TNF- alpha and IFN-gamma using ELISA. Finally, H&E staining of lung tissues was also performed. Key findings A roentgenographically confirmed HAPE model was demonstrated. SULT 1A1 levels are found to be highest in rats suffering HAPE, as previously confirmed in human patients. Inflammation was also assessed based on levels of inflammatory proteins like IL-1b, TNF-a, and IFN-g in addition to H&E staining of lung tissues. Inflammation and HAPE were observed to be synergistic events and not cause and effect of each other. Significance This rat model of HAPE will help researchers and clinicians in evaluating performance of therapies, potential biomarker and also further elucidate underlying molecular processes causing HAPE.

This study aims to identify the challenges and approaches to improve a multicultural competency among teachers in multi-ethnic schools environment based on school leaders’ perspective. Data collection method used in this study is qualitative method. A total of nine school leaders from the states of Kedah, Penang, and Perak were included in the interview session. The results of this study show that the challenges faced by teachers in practicing the multicultural competency are lack of experience toward cultural diversity. A late exposure to cultural diversity makes it difficult for teachers to accept and adapt in a multi-ethnic school environment. The approaches suggested by school leaders to improve the multicultural competency are as follows: (1) Courses on cultural diversity should be organized to enhance the knowledge about cultural diversity; (2) the development of more open and better policy for education system in Malaysia in order to prepare teachers with a higher multicultural competency for teach...

Hypobaric Hypoxia (HH) is an established risk factor for various neuro-physiological perturbations including cognitive impairment. The origin and mechanistic basis of such responses however remain elusive. We here combined systems level analysis with classical neuro-physiological approaches, in a rat model system, to understand pathological responses of brain to HH. Unbiased ‘statistical co-expression networks’ generated utilizing temporal, differential transcriptome signatures of hippocampus—centrally involved in regulating cognition—implicated perturbation of Glio-Vascular homeostasis during early responses to HH, with concurrent modulation of vasomodulatory, hemostatic and proteolytic processes. Further, multiple lines of experimental evidence from ultra-structural, immuno-histological, substrate-zymography and barrier function studies unambiguously supported this proposition. Interestingly, we show a significant lowering of H2S levels in the brain, under chronic HH conditions. This phenomenon functionally impacted hypoxia-induced modulation of cerebral blood flow (hypoxic autoregulation) besides perturbing the strength of functional hyperemia responses. The augmentation of H2S levels, during HH conditions, remarkably preserved Glio-Vascular homeostasis and key neuro-physiological functions (cerebral blood flow, functional hyperemia and spatial memory) besides curtailing HH-induced neuronal apoptosis in hippocampus. Our data thus revealed causal role of H2S during HH-induced early Glio-Vascular dysfunction and consequent cognitive impairment., Highlights • Glio-Vascular dysfunction temporally precedes Hypobaric Hypoxia (HH) induced neuro-pathological effects. • Exposure to HH significantly lowers the levels of H2S in brain. • Augmentation of H2S, utilizing its donor, preserves Glio-Vascular homeostasis and curtails HH-induced memory impairment. The exposure to Hypobaric Hypoxia (HH) environment (such as that encountered by humans at high altitude) culminates in cognitive impairment in an altitude- and duration-dependent manner. The mechanistic basis for such effects, however, remains elusive. Our present study showed that HH-induced neuro-pathological perturbations are temporally preceded by Glio-Vascular dysfunction and are concomitant with lowered levels of gaseous messenger, H2S, in brain. The maintenance of H2S levels (utilizing a specific donor, NaHS) during hypoxia curtailed HH-induced brain-vascular dysfunction and ensuing neuro-pathological effects (on spatial memory). Interestingly, identification of origin of disease in the present study effectively revealed a possible interventional strategy.

This study was conducted to identify factors of social media use as a healthy lifestyle practice among Universiti Malaysia Perlis (UniMAP) students’. This study used a quantitative approach. About 100 UniMAP students’ were involved in answering the research questionnaire. The results show that WhatsApp is the most commonly used by UniMAP students. The findings of this study shows that there is a significant relationship between interaction factors with healthy lifestyle practices among UniMAP students. The findings of this study also shows that there is a significant relationship between information factors with healthy lifestyle practices among UniMAP students. Based on the result in this study, its shows that social media is not only used for entertainment or social purposes but also for healthy lifestyle practice.