Occupational challenges in extreme environment

Ensuring the nutritional security of combatants guarding the extreme altitudes along the Himalayan frontiers remains a daunting task owing to the harsh cold desert climatic conditions, landlocked terrain and sparse vegetation. These cold arid regions are characterized by rugged topography, extreme temperature variations, low precipitation, high wind velocity, thin atmosphere with high UV-radiation and fragile ecosystem. The Defence Life Science Journal decides to bring out a special issue on the theme ‘Cold Arid Agro-Animal Technologies’ focusing on the significance of agro-animal technologies for nutritional security of the soldiers deployed in inhospitable environments as well as the local population who have been living and thriving in these harsh conditions of high altitude

Food Nanotechnologies: Purchasing a Double Edge Sword

Rapid development of nanotechnology has revolutionsed various areas of conventional food science and food industry. The novel properties of nanoparticles (NPs) have led to increasing application of nanotechnology in food industry. Nanofood market have a variety of products like the creamy ice-cream, drinks with no fat, enhanced flavour with nutrients and better textured, coloured and fresh looking food. Continuous monitoring for food spoilage or contamination is possible too. Nanotechnology has transformed the food industries which claim health benefits along with better taste. With the increasing use of NPs especially in food products, where humans are in close contact of the engineered nanomaterials (NMs), it is important to ensure safety before use. Bio-nano interactions often result in novel reaction and formation of products leading to toxicity. NPs mediated toxicity mainly includes inflammation, oxidative damage and genotoxicity. Prolong use of these particles can cause detrimental effects on health. Presently, due to lack of appropriate guidelines and regulations for food nanotechnology there are uncertainties regarding risk identification. Hence, it is essential to evaluate the consequences of this technology in terms of general public and occupational health risks associated with the manufacture, use and disposal of NMs, before instigating the same in day to day use

Advances in Electromagnetic Therapy for Wound Healing

Understanding the molecular basis of wound healing and tissue regeneration continues to remain as one of the major challenges in modern medicine. There is absolute necessity to unveil the rather elusive mechanism with a special emphasis on the approaches to accelerate wound healing. Low frequency low intensity Pulsed electromagnetic therapy is evidenced to have a significant impact on wound repair and regeneration. It provides a non-invasive reparative technique to treat an injury. In vitro studies reported a significant effect of electromagnetic field on neovascularisation and angiogenesis. There are also many pieces of evidence which support its efficiency in reducing the duration of wound healing and improving the tensile strength of scars. Here, we compared the traditional stigma associated with pulsed electromagnetic fields and weighed them with its potential therapeutic effect on wound healing. Furthermore, we emphasized the need for more focused research to determine the therapeutic strategies and optimised parameters of pulsed electromagnetic field that can assure efficient wound healing and regeneration.

Interactions between the quality control ubiquitin ligase CHIP and ubiquitin conjugating enzymes

<p>Abstract</p> <p>Background</p> <p>Ubiquitin (E3) ligases interact with specific ubiquitin conjugating (E2) enzymes to ubiquitinate particular substrate proteins. As the combination of E2 and E3 dictates the type and biological consequence of ubiquitination, it is important to understand the basis of specificity in E2:E3 interactions. The E3 ligase CHIP interacts with Hsp70 and Hsp90 and ubiquitinates client proteins that are chaperoned by these heat shock proteins. CHIP interacts with two types of E2 enzymes, UbcH5 and Ubc13-Uev1a. It is unclear, however, why CHIP binds these E2 enzymes rather than others, and whether CHIP interacts preferentially with UbcH5 or Ubc13-Uev1a, which form different types of polyubiquitin chains.</p> <p>Results</p> <p>The 2.9 Å crystal structure of the CHIP U-box domain complexed with UbcH5a shows that CHIP binds to UbcH5 and Ubc13 through similar specificity determinants, including a key S-P-A motif on the E2 enzymes. The determinants make different relative contributions to the overall interactions between CHIP and the two E2 enzymes. CHIP undergoes auto-ubiquitination by UbcH5 but not by Ubc13-Uev1a. Instead, CHIP drives the formation of unanchored polyubiquitin by Ubc13-Uev1a. CHIP also interacts productively with the class III E2 enzyme Ube2e2, in which the UbcH5- and Ubc13-binding specificity determinants are highly conserved.</p> <p>Conclusion</p> <p>The CHIP:UbcH5a structure emphasizes the importance of specificity determinants located on the long loops and central helix of the CHIP U-box, and on the N-terminal helix and loops L4 and L7 of its cognate E2 enzymes. The S-P-A motif and other specificity determinants define the set of cognate E2 enzymes for CHIP, which likely includes several Class III E2 enzymes. CHIP's interactions with UbcH5, Ube2e2 and Ubc13-Uev1a are consistent with the notion that Ubc13-Uev1a may work sequentially with other E2 enzymes to carry out K63-linked polyubiquitination of CHIP substrates.</p

Protein Profile of Human Lung Epithelial Cells (A549) Revealing Deviation in Cytoskeleton Proteins in Response to Zinc Oxide Nanoparticles Exposure

Zinc oxide nanoparticles (ZnO NPs) are widely used in biomedicine and scientific research because of their high dissolution property and bioavailability. On the contrary, this property also increases the intracellular reactivity, accessibility and cytotoxicity. These nano-bio interactions could induce undesirable changes in the proteome of the interacting cells, especially in the lung cells as these are the primary contact site. However, the potential effects of ZnO NPs exposure on proteome remain unclear. Proteomics data will substantiate the detailed mechanism of cellular interactions and modulatory effects of ZnO NPs on cells. Quantitative proteomic profiling was done using MALDI-TOF/TOF and MS/MS to identify differential protein expression on exposure to NPs among non exposed and exposed cells. Twenty-two proteins, with approximately 1.5 fold differential expression in cells exposed to ZnO NPs as compared to control cells were identified. Differentially expressed proteins were further classified using PANTHER software on the basis of functional gene ontology term: molecular function, biological process and cellular component. ToppGene suite was used to study protein-protein interaction and network was enriched with STRING. This study is a systematic analysis of protein modulation of the A549 cells exposed to ZnO NPs indicating alterations in the cytoskeleton

Ethyl 4-(4′-heptanoyloxyphenyl)-6-methyl-3,4-dihydropyrimidin-2-one-5-carboxylate Prevents Progression of Monocrotaline-induced Pulmonary Arterial Hypertension in Rats

Therapies to prevent onset and progression of pulmonary arterial pressure are not very effective yet. This study was designed to investigate the effects of a novel dihydropyrimidinone, ethyl 4-(4′-heptanoyloxyphenyl)-6-methyl-3,4-dihydropyrimidin-2-one-5-carboxylate (H-DHPM) on pathogenesis of monocrotaline (MCT)-induced pulmonary arterial hypertension (PAH). For the same purpose, rats were injected intraperitoneally (i.p.) a single dose (60 mg/kg) of MCT which led to development of PAH in 21 days. MCT insult caused high mortality, pulmonary vascular and parenchymal remodelling. Since the course of PAH pathogenesis is characterised by an early onset and progression phases, H-DHPM was administered i.p. at 30 mg/kg dosage in MCT pre-injected animals either from day 0 through day 21 or day 14 though day 21 of MCT injection in two separate treatment groups. H-DHPM significantly improved survival, prevented remodelling of pulmonary vasculature and parenchyma and subsequently ameliorated PAH pathogenesis. Moreover, we observed significant decrease in right ventricle hypertrophy, measured by wet weight of right ventricle (RV) divided by wet weight of left ventricle plus septum (LV+S), in H-DHPM treated groups as compared to MCT injected animals. These findings suggest H-DHPM not only prevented development of PAH but also treated the PAH pathogenesis in progressive phase. In conclusion, our data determines H-DHPM, might be a future drug for the prevention of PAH

Structural basis of nucleotide exchange and client binding by the Hsp70 cochaperone Bag2

Cochaperones are essential for Hsp70/Hsc70-mediated folding of proteins and include nucleotide exchange factors (NEF) that assist protein folding by accelerating ADP/ATP exchange on Hsp70. The cochaperone Bag2 binds misfolded Hsp70 clients and also acts as a NEF, but the molecular basis of its functions is unclear. We show that, rather than being a member of the Bag domain family, Bag2 contains a new type of Hsp70 NEF domain, which we call the “Brand New Bag” (BNB) domain. Free and Hsc70-bound crystal structures of Bag2-BNB show its dimeric structure in which a flanking linker helix and loop bind to Hsc70 to promote nucleotide exchange. NMR analysis demonstrates that the client-binding sites and Hsc70 interaction sites of Bag2-BNB overlap, and that Hsc70 can displace clients from Bag2-BNB, indicating a distinct mechanism for the regulation of Hsp-70-mediated protein folding by Bag2

Hypobaric Hypoxia Imbalances Mitochondrial Dynamics in Rat Brain Hippocampus

Brain is predominantly susceptible to oxidative stress and mitochondrial dysfunction during hypobaric hypoxia, and therefore undergoes neurodegeneration due to energy crisis. Evidences illustrate a high degree of association for mitochondrial fusion/fission imbalance and mitochondrial dysfunction. Mitochondrial fusion/fission is a recently reported dynamic mechanism which frequently occurs among cellular mitochondrial network. Hence, the study investigated the temporal alteration and involvement of abnormal mitochondrial dynamics (fusion/fission) along with disturbed mitochondrial functionality during chronic exposure to hypobaric hypoxia (HH). The Sprague-Dawley rats were exposed to simulated high altitude equivalent to 25000 ft for 3, 7, 14, 21, and 28 days. Mitochondrial morphology, distribution within neurons, enzyme activity of respiratory complexes, Δψm, ADP: ATP, and expression of fission/fusion key proteins were determined. Results demonstrated HH induced alteration in mitochondrial morphology by damaged, small mitochondria observed in neurons with disturbance of mitochondrial functionality and reduced mitochondrial density in neuronal processes manifested by excessive mitochondrial fragmentation (fission) and decreased mitochondrial fusion as compared to unexposed rat brain hippocampus. The study suggested that imbalance in mitochondrial dynamics is one of the noteworthy mechanisms occurring in hippocampal neurons during HH insult

Hypobaric Hypoxia Imbalances Mitochondrial Dynamics in Rat Brain Hippocampus

Brain is predominantly susceptible to oxidative stress and mitochondrial dysfunction during hypobaric hypoxia, and therefore undergoes neurodegeneration due to energy crisis. Evidences illustrate a high degree of association for mitochondrial fusion/fission imbalance and mitochondrial dysfunction. Mitochondrial fusion/fission is a recently reported dynamic mechanism which frequently occurs among cellular mitochondrial network. Hence, the study investigated the temporal alteration and involvement of abnormal mitochondrial dynamics (fusion/fission) along with disturbed mitochondrial functionality during chronic exposure to hypobaric hypoxia (HH). The Sprague-Dawley rats were exposed to simulated high altitude equivalent to 25000 ft for 3, 7, 14, 21, and 28 days. Mitochondrial morphology, distribution within neurons, enzyme activity of respiratory complexes, Δψm, ADP: ATP, and expression of fission/fusion key proteins were determined. Results demonstrated HH induced alteration in mitochondrial morphology by damaged, small mitochondria observed in neurons with disturbance of mitochondrial functionality and reduced mitochondrial density in neuronal processes manifested by excessive mitochondrial fragmentation (fission) and decreased mitochondrial fusion as compared to unexposed rat brain hippocampus. The study suggested that imbalance in mitochondrial dynamics is one of the noteworthy mechanisms occurring in hippocampal neurons during HH insult