GLOBAL WARMING CHALLENGES AND TACTICAL RAMIFICATIONS: ADDRESSING ECOLOGICAL SECURITY CONCERNS

Humanity has been facing frequent trials in the contemporary era. One seriously emerging challenge is global warming. It has a record of disastrous impacts on earth that are severe and cataclysmic. The Intergovernmental Panel on Climate Change attributes mega-disasters to global warming. These environmental calamities have raised serious concerns for leaders, scientists, environmentalists as well as public. The defence experts warn about gradually changing weather tendencies and emerging of new security challenges. Global warming is causing continuous fluctuations in our fragile ecosystem, and any persistent malfunctioning in the ecosystem would affect the politico-economic, strategic, and even very existence of humanity. It would require rational choices and new strategic approaches for saving humanity and numerous organism species under global warming impacts. Strategists, in the future, will inevitably explore looming tactical security concerns to safeguard defence capabilities. Against this backdrop, this paper argues that global warming will create severe strategic complications. In the coming decades, traditional national defence systems will have to undergo a new transformation supportive to cope with emerging cataclysmic security issues due to global warming. Therefore, innovative lines of tactical ecological rationale will become an essential part of national defence.   Bibliography Entry Shah, Syed Muhammad Ali, Shaheen Akhtar, and Fozia Bibi. 2021. "Global Warming Challenges and Tactical Ramifications: Addressing Ecological Security Concerns." Margalla Papers 25 (1): 12-22

Extra-nuclear telomerase reverse transcriptase (TERT) regulates glucose transport in skeletal muscle cells

Telomerase reverse transcriptase (TERT) is a key component of the telomerase complex. By lengthening telomeres in DNA strands, TERT increases senescent cell lifespan. Mice that lack TERT age much faster and exhibit age-related conditions such as osteoporosis, diabetes and neurodegeneration. Accelerated telomere shortening in both human and animal models has been documented in conditions associated with insulin resistance, including T2DM. We investigated the role of TERT, in regulating cellular glucose utilisation by using the myoblastoma cell line C2C12, as well as primary mouse and human skeletal muscle cells. Inhibition of TERT expression or activity by using siRNA (100. nM) or specific inhibitors (100. nM) reduced basal 2-deoxyglucose uptake by ~. 50%, in all cell types, without altering insulin responsiveness. In contrast, TERT over-expression increased glucose uptake by 3.25-fold. In C2C12 cells TERT protein was mostly localised intracellularly and stimulation of cells with insulin induced translocation to the plasma membrane. Furthermore, co-immunoprecipitation experiments in C2C12 cells showed that TERT was constitutively associated with glucose transporters (GLUTs) 1, 4 and 12 via an insulin insensitive interaction that also did not require intact PI3-K and mTOR pathways. Collectively, these findings identified a novel extra-nuclear function of TERT that regulates an insulin-insensitive pathway involved in glucose uptake in human and mouse skeletal muscle cells

Lipid Profiles and Its Association with Pre-Eclampsia and Eclampsia in Nulliparous Pregnant Women

Objectives: To access the lipid profiles and its association with pre-eclampsia and eclampsia in nulliparous pregnant women. Material and Methods: This cross-sectional study was performed on 234 nulliparous pregnant women with gestation period of  > 20 weeks and aged 15-45 years, from March to October 2014, in Institute of Basic Medical Sciences (IBMS), Khyber Medical University (KMU), Peshawar, Pakistan with cooperation from gynecology and obstetrics departments of three tertiary-care hospitals of Peshawar & Khyber Medical College, Peshawar,  Khyber Pakhtunkhwa (KP), Pakistan. Subjects were assigned to three groups i.e., group A, group B and group C. For performing biochemical assays and lipid profiling, through ELISA, blood samples were collected from already subjects both with the disease and the controls. Results: Both subjects having pre-eclampsia and eclampsia showed significant elevated levels (p < 0.001) for low density lipoproteins cholesterols (LDL-c), high density lipoprotein cholesterol (HDL-c), total cholesterol (TC)/HDL-c and LDL-c/HDL-c ratio. But TC of pre-eclampsia subjects were found significantly elevated (p < 0.001) in relation to controls. LDL-c/HDL-c and TC/HDL-c also revealed an elevated significant change (p < 0.001) both for pre-eclamptic and eclamptic subjects. On the other hand, only TG/HDL-c in pre-eclamptic patients was found significantly higher (p<0.004) when compared to control group.  Conclusion: Serum lipid levels were observed higher in pre-eclampsia and eclampsia patients hence an early assessment is necessary to prevent complications in such patients

Structural, surface morphology, dielectric and magnetic properties of holmium doped BiFeO3 thin films prepared by pulsed laser deposition

In this work, Bi1-xHoxFeO3 (with x = 0, 0.05, 0.10, 0.15 and 0.20) thin films were successfully grown on Si (100) substrates using pulsed laser deposition and the effect of Ho doping on the crystal structure, dielectric and magnetic properties were studied. X-ray diffraction studies on undoped BiFeO3 confirmed the presence of a rhombohedral phase with crystallite sizes in the 14–24 nm range. The surface morphology and microstructure of the thin films were analysed by field emission scanning electron microscopy and atomic force microscopy. The results reveal that the grain size decreases as the Ho doping concentration increases. X-ray photoemission spectroscopy was used to identify the chemical bonding, valance band and core levels of Ho doped BiFeO3 thin films. Dielectric constant and loss in Ho doped samples has been measured using a vector network analyzer and shows good dielectric behaviour compared to undoped BiFeO3. A vibrating sample magnetometer was used to investigate the magnetic properties for Ho doping with concentrations of x ≥ 0.15. In comparison to undoped BiFeO3, the doped films exhibited larger remanence and saturation magnetization. The enhancement of these properties due to Ho doping is discussed along with their relevance in designing multiferroic materials based on Bi1-xHoxFeO3 films for magnetic field sensors, multiple-state memories and spintronic elements

Tissue Glucocorticoid Metabolism in Adrenal Insufficiency:A Prospective Study of Dual-release Hydrocortisone Therapy

Background: Patients with adrenal insufficiency (AI) require life-long glucocorticoid (GC) replacement therapy. Within tissues, cortisol (F) availability is under the control of the isozymes of 11β-hydroxysteroid dehydrogenase (11β-HSD). We hypothesize that corticosteroid metabolism is altered in patients with AI because of the nonphysiological pattern of current immediate release hydrocortisone (IR-HC) replacement therapy. The use of a once-daily dual-release hydrocortisone (DR-HC) preparation, (Plenadren®), offers a more physiological cortisol profile and may alter corticosteroid metabolism in vivo.Study Design and Methods: Prospective crossover study assessing the impact of 12 weeks of DR-HC on systemic GC metabolism (urinary steroid metabolome profiling), cortisol activation in the liver (cortisone acetate challenge test), and subcutaneous adipose tissue (microdialysis, biopsy for gene expression analysis) in 51 patients with AI (primary and secondary) in comparison to IR-HC treatment and age- and BMI-matched controls.Results: Patients with AI receiving IR-HC had a higher median 24-hour urinary excretion of cortisol compared with healthy controls (72.1 µg/24 hours [IQR 43.6-124.2] vs 51.9 µg/24 hours [35.5-72.3], P = .02), with lower global activity of 11β-HSD2 and higher 5-alpha reductase activity. Following the switch from IR-HC to DR-HC therapy, there was a significant reduction in urinary cortisol and total GC metabolite excretion, which was most significant in the evening. There was an increase in 11β-HSD2 activity. Hepatic 11β-HSD1 activity was not significantly altered after switching to DR-HC, but there was a significant reduction in the expression and activity of 11β-HSD1 in subcutaneous adipose tissue.Conclusion: Using comprehensive in vivo techniques, we have demonstrated abnormalities in corticosteroid metabolism in patients with primary and secondary AI receiving IR-HC. This dysregulation of pre-receptor glucocorticoid metabolism results in enhanced glucocorticoid activation in adipose tissue, which was ameliorated by treatment with DR-HC

Mapping the Steroid Response to Major Trauma From Injury to Recovery : A Prospective Cohort Study

CONTEXT: Survival rates after severe injury are improving, but complication rates and outcomes are variable. OBJECTIVE: This cohort study addressed the lack of longitudinal data on the steroid response to major trauma and during recovery. DESIGN: We undertook a prospective, observational cohort study from time of injury to 6 months postinjury at a major UK trauma centre and a military rehabilitation unit, studying patients within 24 hours of major trauma (estimated New Injury Severity Score (NISS) > 15). MAIN OUTCOME MEASURES: We measured adrenal and gonadal steroids in serum and 24-hour urine by mass spectrometry, assessed muscle loss by ultrasound and nitrogen excretion, and recorded clinical outcomes (ventilator days, length of hospital stay, opioid use, incidence of organ dysfunction, and sepsis); results were analyzed by generalized mixed-effect linear models. FINDINGS: We screened 996 multiple injured adults, approached 106, and recruited 95 eligible patients; 87 survived. We analyzed all male survivors <50 years not treated with steroids (N = 60; median age 27 [interquartile range 24-31] years; median NISS 34 [29-44]). Urinary nitrogen excretion and muscle loss peaked after 1 and 6 weeks, respectively. Serum testosterone, dehydroepiandrosterone, and dehydroepiandrosterone sulfate decreased immediately after trauma and took 2, 4, and more than 6 months, respectively, to recover; opioid treatment delayed dehydroepiandrosterone recovery in a dose-dependent fashion. Androgens and precursors correlated with SOFA score and probability of sepsis. CONCLUSION: The catabolic response to severe injury was accompanied by acute and sustained androgen suppression. Whether androgen supplementation improves health outcomes after major trauma requires further investigation

Interactions between telomerase reverse transcriptase (TERT) and insulin signalling in muscle

Ageing is a well established risk factor for the development of the metabolic syndrome and type 2 diabetes (T2DM). It is well-recognised that there is an increase in insulin resistance with age, and disturbances in insulin signalling have been shown to affect both insulin sensitivity and lifespan. A decrease in mean telomere length provides a marker for biological age at the cellular level. Accelerated telomere shortening in both human and animal models has been documented in conditions associated with insulin resistance, including T2DM. Maintenance of telomere length is dependent on the activity of the enzyme telomerase (which is dependent on the expression of its catalytic protein TERT) which can help reverse this process and extend the lifespan of cells. When acting in this capacity, TERT is a nuclear protein, but recently it has been shown to possess the ability to shuttle between the nucleus and cytoplasm. The present study was performed with the aim of determining a possible role of TERT in insulin signalling in C2C12, primary mouse and human skeletal muscle cells. Confocal microscopy was used to study protein localisation; in parallel, changes in glucose uptake were determined by measuring 2-deoxyglucose. TERT protein in C2C12 cells was mostly non-nuclear (cytosolic) in localisation, and translocated to the plasma membrane in response to insulin. This translocation was inhibited by wortmannin and rapamycin indicating that this process was dependent on PI3K signalling (as is the insulin induced translocation of GLUT4) and also dependent on mTOR signalling. Altering TERT expression, through over-expression or RNAi-induced knock-down changed the intracellular distribution of GLUT1, GLUT4 and GLUT12, in a similar manner to the effect of insulin. GLUT1 and GLUT4 responded to insulin as expected in all the three cell systems, but there was a difference in the response of the recently identified GLUT12. GLUT12 in the C2C12 cells in the basal state was distributed throughout the cytoplasm and following insulin addition, became localised to peri-nuclear punctuate structures. By contrast, GLUT12 was localised to the plasma membrane (with some cytoplasmic presence) in primary mouse skeletal muscle tissue sections. Interestingly, under conditions of reduced plasma insulin levels in these mouse muscle sections GLUT12 remained abundantly present at the plasma membrane. Contrary to its actions in the C2C12 cells, insulin caused GLUT12 to mobilise from sub-plasma membrane pools and to translocate towards the plasma membrane in the human skeletal muscle cells. Furthermore, knocking-down GLUT12 expression in the C2C12 and primary mouse skeletal muscle cells decreased both basal and insulin dependent 2-deoxyglucose uptake. These observations suggest that this transporter may contribute towards overall glucose transport, but responds differently to an insulin stimulus in the C2C12 cells than in the primary mouse and human skeletal muscle cells. Importantly, GLUT12 distribution and expression were affected by a reduction in mTOR expression, but again there was a variation in the response between the C2C12 cells and both the other cell systems. However, over-expressing TERT increased 2-deoxyglucose uptake synergistically with the effect of insulin in all three cell systems. This increase in glucose transport was shown to be partly through the involvement of GLUT12, as knocking-down GLUT12 expression accounted for part of the increase in 2-deoxyglucose uptake seen in response to TERT over-expression. TERT protein was found to co-immunoprecipitate with all three glucose transporter proteins studied, suggesting that the effects of changes in TERT expression on GLUT intracellular localisation and glucose transport may be due to TERT-GLUT molecular interactions. Importantly, exposure to inhibitors of mTOR, PI3K and TERT did not diminish the ability of TERT to co-immunoprecipitate with GLUT1 and GLUT4 protein(s). However, geldanamycin, a Hsp90 inhibitor diminished the TERT-GLUT12 interaction, implying that the TERT-Hsp90-RAPTOR-mTOR complex formation may be important for this interaction. These findings suggest the existence of a novel extra-nuclear function of TERT and a possible mechanism that appears to regulate glucose transport, acting synergistically with insulin signalling. Although, TERT interacts with all the GLUT proteins studied, it appears to affect GLUT12 differently to GLUT1 and GLUT4 to regulate glucose transport and mTOR signalling appears to be important for GLUT12 function. Therefore, these results raise the prospect of the existence of a link between alterations in the extra-nuclear distribution of TERT and changes in insulin-dependent glucose transport