Role of a-Synuclein in Cell Biology: A Hypothesis and its Implications in Neurodegenerative Diseases

I wish to suggest a physiological function for alpha-synuclein (a-syn) that has the potential to explain its role in pathology. Intraneuronal proteinaceous Lewy Bodies (LBs), the pathological hallmark of Parkinson’s disease and other synucleinopathies, consist majorly of a-syn. Ample evidence suggests that LBs are not the result of simple amyloidosis of cytosolic a-syn. Benign soluble unstructured a-syn gets converted into toxic species which preferentially accumulates in LBs. But how these aberrant a-syn molecules are produced in the cytosol, is still not clear. The present hypothesis is an effort to relate a metabolic reaction specific to neuronal function, that is, phase transition, with the pathobiology of a-syn. During high frequency stimulation, which entails rapid phase transition reactions at the presynaptic compartment, aberrant interaction of a-syn with the membrane occasionally generates toxic a-syn molecules. My conjecture is that the physiological function of a-syn is to modulate membrane fluidity by a process wherein it goes through a conformation cycle driven by a flux of energy from mitochondria. It is the range of toxic a-syn produced during aberrant phase transition reaction that is responsible for pathology, not the normal a-syn that reenters the conformation cycle, thereby, resolving the paradox of the Janus-face of a-syn.

EVALUATION OF CLINICAL AWARENESS OF DIABETIC MELLITUS AMONG RAKMHSU MEDICAL STUDENTS- A QUESTIONNAIRE SURVEY

Introduction: The number of patients with diabetes are increasing in rapid phase and the present medical students will encounter with such patients in the future very often. It was essential to understand and update their knowledge through education and awareness programs. Materials and methods: The cross-sectional questionnaire survey has been conducted in RAK Medical and Health Sciences University (RAKMHSU) with due approval from research ethics committee. After going through various indexed articles related to our topic, a pre designed pre validated questionnaire was prepared. The questionnaire assessed the knowledge about symptoms, investigations, treatment and complications. This was applied after validation to second, third, fourth and fifth year medical students. Results: The study showed the majority in both groups 93.5% and 89.2% agreed that they will be involved in taking care of diabetic patients in their future practice. The study also found that 65.2% group A agreed that excessive thirst and urination is a indicative of low blood sugar when compared with 31.7% from group B. With regard to symptoms majority in both groups agreed itchy skin is not a symptom of DM. When asked about insulin misuse, only 36.8% and 55.4% students agreed that blood glucose will go below 50mg/dl. Discussion and conclusion: Our study correlated with various studies which showed many students had problems in treatment aspects. But we also had positive results which correlated with other study showing they have good knowledge about symptoms. We also found our students had good knowledge about diabetic ketoacidosis. In conclusion, there is a need for conducting regular workshops, seminars, conferences in medical colleges to upgrade the knowledge of students and make them a competent general physician. Key words: Diabetes, Keto acidosis, Education, Knowledge, Risk factors

SIRT1 Inhibition Impairs Ca2+ Buffering in Coronary Smooth Muscle Cells of Ossabaw Miniature Swine

Background: SIRT1 is a deacetylase that has diverse roles in intracellular Ca2+ signaling, metabolism, and cardiovascular disease. SIRT1 increases sarco-endoplasmic reticulum Ca2+ ATPase (SERCA) activity that is essential to buffer the increase in Ca2+ induced by release from the sarcoplasmic reticulum (SR). Our lab has shown that metabolic syndrome (MetS) impairs SERCA activity in coronary smooth muscle cells and causes coronary artery disease in Ossabaw miniature swine. We hypothesized that SIRT1 inhibition and MetS would impair Ca2+ buffering. Methods: CRISPR/Cas9 methods delivered a leucine to proline point mutation in SIRT1 (SIRT1L100P) into the Ossabaw swine genome to compare to wild type (WT) and mimic the naturally occurring mutation in humans and decrease SIRT1 activity. Four treatment groups of juvenile swine were based on genotype and diet: WT Lean, SIRT1 Lean, WT MetS, and SIRT1 MetS. Lean swine were fed normal chow and MetS were fed a hypercaloric, atherogenic diet for 7 months. The left anterior descending coronary artery was harvested and enzymatically digested to obtain cells. Fluorescence microscopy measured the Ca2+ indicator fura-2 in single cells. The cells were exposed to 5 mM caffeine to maximally release stores of Ca2+ from the SR. Ca2+ buffering capacity of each cell was analyzed after the caffeine-induced peak increase to assess Ca2+ efflux and SERCA activity. Results: MetS was confirmed by increased body weight, impaired glucose tolerance, hyperinsulinemia, and hypercholesterolemia. Coronary atherosclerosis was shown by angiography, intravascular ultrasound, and gross imaging. The rapid phase of Ca2+ buffering due to Ca2+ efflux was not affected by SIRT1 mutation or MetS. The slower phase of Ca2+ buffering due to SERCA activity was impaired only by SIRT1 mutation (p<0.0005), not by MetS. Conclusion: SIRT1 mutation alone inhibited SERCA buffering of Ca2+ in coronary smooth muscle. (Support: NIH T35HL110854, DK120240, DK09751.)

Effect of off-stoichiometry on the thermal conductivity of amorphous GeTe

The reversible phase change of Germanium Telluride (GeTe) is essential for developing advanced non-volatile devices. We investigate off-stoichiometric effect on the thermal and structural properties of amorphous Ge$_{1-\delta}$Te (0 $\le$ $\delta$ $\le$ 0.12) via molecular dynamics. The structural optimization due to off-stoichiometry was taken into account with an empirical potential. Our simulated thermal conductivity is in the range of experimental observations. With increasing $\delta$, the thermal conductivity tends to be slightly reduced. Analysis on the coordinate number and the bond angle distribution indicates that the off-stoichiometric Ge$_{1-\delta}$Te still retain its ability of rapid phase transition. These results are helpful in reliable device design and modeling.

Thermo-optical reaction changes of a PCM filled glass system

This paper analyzes thermo-optical reactions of the PCM-based glass element which has the capability to store thermal energy together with a variable transparency level through the energy storage process corresponding to phase change. Optical properties are determined by the level of phase transition at given boundary conditions over time. Special uncommon thermo-optical changes occur during its internal phase transition processes, from liquid to solid phase and vice versa (latent heat of fusion) within a given narrow range of temperature interval. PCM acts as random and diffusive media with relevant scattering effects in solid phase, however in liquid state are highly transparent with direct transmission and no relevant scattering effect. These internal physical changes were detailly identified by experimental test procedures based on optical properties measurements performed using a spectrophotometry, and parallelly with the stabilization of each temperature set provided by environmental chamber. As result of that, relevant differences in the PCM spectral feature can be identified for its different states (solid/liquid) in which transmittance spectra are unstable during rapid phase change process. This provides a substantial base line for the optimization of a PCM glazing system in terms of various degree of freedom for different building types and climate zones.

Strengthening Gender Justice in a Just Transition: A Research Agenda Based on a Systematic Map of Gender in Coal Transitions

For climate change mitigation, a rapid phase-out of fossil fuels such as coal is necessary. This has far-reaching gender-specific consequences. This paper presents a systematic map of the literature that examines the impact of historical coal phase-out processes on women and their role in these processes. The search process consisted of screening over 3100 abstracts and reading 247 full-text studies. The analysis of the 73 publications ultimately included in the systematic map shows that past coal phase-outs meant both opportunities (e.g., increased labour market participation) as well as burdens for women (e.g., double burden of job and household). It becomes clear that agency within coal transitions was also gendered. For example, it was difficult for women to gain access to union structures, which led them to organise themselves into grassroots movements. Our research shows that policies aiming for a just sustainability transition should always be explicitly gender-responsive. However, the impact of sustainability transitions on women’s lives remains largely under-researched. Therefore, we propose a research agenda based on our findings containing six key issues that need to be addressed scientifically.

Budbreak patterns and phytohormone dynamics reveal different modes of action between hydrogen cyanamide- and defoliant-induced flower budbreak in blueberry under inadequate chilling conditions

Under inadequate chilling conditions, hydrogen cyanamide (HC) is often used to promote budbreak and improve earliness of Southern highbush blueberry (Vaccinium corymbosum L. interspecific hybrids). However, HC is strictly regulated or even banned in some countries because of its high hazardous properties. Development of safer and effective alternatives to HC is critical to sustainable subtropical blueberry production. In this study, we examined the efficacy of HC and defoliants as bud dormancy-breaking agents for ‘Emerald’ blueberry. First, we compared water control, 1.0% HC (9.35 L ha–1), and three defoliants [potassium thiosulfate (KTS), urea, and zinc sulfate (ZS)] applied at 6.0% (28 kg ha–1). Model fitting analysis revealed that only HC and ZS advanced both defoliation and budbreak compared with the water control. HC-induced budbreak showed an exponential plateau function with a rapid phase occurring from 0 to 22 days after treatment (DAT), whereas ZS-induced budbreak showed a sigmoidal function with a rapid phase occurring from 15 to 44 DAT. The final budbreak percentage was similar in all treatments (71.7%–83.7%). Compared with the water control, HC and ZS increased yield by up to 171% and 41%, respectively, but the yield increase was statistically significant only for HC. Phytohormone profiling was performed for water-, HC- and ZS-treated flower buds. Both chemicals did not increase gibberellin 4 and indole-3-acetic acid production, but they caused a steady increase in jasmonic acid (JA) during budbreak. Compared with ZS, HC increased JA production to a greater extent and was the only chemical that reduced abscisic acid (ABA) concentrations during budbreak. A follow-up experiment tested ZS at six different rates (0–187 kg ha–1) but detected no significant dose-response on budbreak. These results collectively suggest that defoliants are not effective alternatives to HC, and that HC and ZS have different modes of action in budbreak induction. The high efficacy of HC as a dormancy-breaking agent could be due to its ability to reduce ABA concentrations in buds. Our results also suggest that JA accumulation is involved in budbreak induction in blueberry.