Stress-Dependent Regulation Of A Major Node Of The Insulin-Like Peptide Network That Modulates Survival

Chronic stress disrupts insulin signaling, predisposing human populations to diabetes, cardiovascular disease, Alzheimer’s Disease, and other metabolic and neurological disorders, including post-traumatic disorders (PTSD). Thus, efficient recovery from stress optimizes survival. However, stress recovery in humans is difficult to study, but is much easier to dissect in model organisms. The worm genetic model Caenorhabditis elegans can switch between stressed and non-stressed states, and this switch is largely regulated by insulin signaling. Previously, the Alcedo lab proposed that insulin-like peptides (ILPs), which exist as multiple members of a protein family in both C. elegans and humans, implements a combinatorial coding strategy to control the switch between the two physiological states. The concept of combinatorial coding has led to the identification of an inter-ILP network, where one ILP, ins-6, is a major node of the network. This is consistent with ins-6 as the most pleotropic of all ILPs that have been tested. ins-6 has also been shown to be the most important ILP in promoting stress recovery in C. elegans. Because of its central role in the ILP network and in stress recovery, for my thesis I identified mechanisms through which INS-6 regulates the network and an animal’s recovery from stress. Under optimal environments, ins-6 mRNA is endogenously expressed in the cell bodies of one or two chemosensory neurons, ASI and ASJ, in the developing animal. However, upon stress-induced developmental arrest, known as dauer, ins-6 mRNA is only limited to the ASJ sensory neurons. I discovered that ins-6 mRNA from ASJ is also surprisingly transported to the axonal nerve ring bundle of stressed animals, but lost from the nerve ring after recovery from stress. Consistent with the existence of an inter-ILP network, insulin signaling regulates ins-6 mRNA transport, which also requires the activities of specific kinesins. This transport additionally depends on the untranslated regions of ins-6 mRNA, but these regions are insufficient for transport. More importantly and in collaboration with other members of the Alcedo lab, we showed that axonal ins-6 mRNA facilitates stress recovery, where high axonal ins-6 mRNA promotes faster recovery and low axonal ins-6 mRNA delays recovery. Moreover, I demonstrated the existence of axonal Golgi bodies, whose mobilization are enhanced during stress. Together my data suggest that stress stimulates the axonal transport of ILP mRNAs, which are then locally translated and packaged for secretion--a mechanism that promotes plasticity during stress and optimal stress recovery. To identify additional regulators of ins-6 mRNA, I also performed, together with other members of the lab, a forward genetic screen for mutants that alter ins-6 transcription during stress. Through whole-genome sequencing, one of the five mutants we isolated is potentially a mutation in an innexin gap junction protein. Since innexins have been shown to regulate neural activity, I tested the hypothesis that neural activity will also affect axonal ins-6 mRNA transport. Interestingly, I found that a synaptic transmission mutant, which should have low neural activity, increases axonal ins-6 mRNA and alters neurite morphology. My thesis study raises an intriguing hypothesis: stress modulates neurite activity and morphology, which in turn promote ILP mRNA transport to the axons. The axonal localization of an ILP mRNA also uncovers a novel mechanism of insulin signaling during stress. Because of the high degree of conservation between C. elegans and humans and the effects of altered insulin signaling in stressed brains, my findings should advance our understanding of how a nervous system recovers from stress. The work described in this thesis should lead to potential therapies for stress management to promote better health

Prediction of dissolution time of gerromanganese in hot metal and steel bath

Mathematical models enable us to study metallurgical processes in depth. Significant improvements in plant operation cannot, in general, be brought about without quantification of the impact of the operating parameters on the end product. It is for this reason that mathemati-cal models have become popular in the steel industry, particularly with the advent of low-cost, high speed personal computers. Another reason why modelling is necessary is because increasingly alterations in operating parameters have to be made to bring about changes in heat or mass transfer. The gut-feelings of the plant operator are no longer able to deliver the goods because such feelings are developed by repeated exposure to quanti-fiable changes in the process brought about by alterat-ions, deliberate or otherwise, in the operating parameters. Some of these basic parameters are not measured, for example heat transfer coefficient in case of a solid particle dissolving in a liquid bath, and therefore it would be futile to expect gut-feelings to offer solutions as to how dissolution time would be effected by a change in the type of ferroalloy or by change in its size. The deter-mination of the dissolution time of ferroalloys is import-ant as it indicates to the process control engineer the minimum time necessary before the bath can be subjected to the next step of processing. Changes in the bath superheat; the size and the initial temperature of the ferroalloy and the bath hydrodynamics influence the dissolution time. Determining this dissolution time by experimentation is extremely difficult and would involve a series of experi-ments with different types of ferroalloys under varying conditions. On the other hand, the dissolution time can be obtained using a mathematical model of the dissolution kinetics of ferroalloys which after proper validation can be used to assess the dissolution behaviour of the ferro-alloy under a variety of conditions. At TATA STEEL blast furnace hot metal is used to cast ingot molds. The com-position of the blast furnace hot metal desired for making ingot moulds demands the addition of 20 kg each of ferro-manganese & ferro-silicon in the 12 tonne transfer ladles into which the blast furnace metal is poured at the ingot mould foundry (IMF). Owing to the low temperature of hot metal at IMF, casting commences immediately and a complete dissolution of the ferroalloy is often not possible. A mathematical model for calculating dissolution time for a solid particle in a liquid metal has been developed at R&D Division of Tata Steel. The model has been developed with the feasibility of predicting dissolution times for eases where the ferroalloy has a melting point lower as well as higher than the bath temperature. The model has been validated against data published in literature and applied to predict dissolution times of ferroalloys in steel and blast furnace hot metal. This model was used to study dissolution of ferroalloys in foundry and to evolve suitable corrective measures. On the basis of this study additions are being optimized at the IMF in' Tata Steel

PURIFICATION AND CHARACTERIZATION OF a-GLUCOSIDASE FROM MOSS HYOPHILLA NYMANIANA (FLEISH.) MENZEL

Objective: The present study was undertaken to extract and purify α-glucosidase N-linked glycosylation enzyme from moss Hyophilla nymaniana(Fleish.) Menzel.Methods: Frozen protonemal cells were taken for crude enzyme extraction, and the enzyme α-glucosidase was purified from the prepared crudeenzyme extract by ammonium sulfate (NH4) 2SO4 precipitation, gel filtration and finally on diethylaminoethyl sephadex column chromatography.Results: The final purification step of the enzyme resulted in 35 fold purification with a recovery of 4%. A single protein band of 72±5 kilodalton wasseen on 10% sodium dodecyl sulfate-polyacrylamide gel electrophoresis. The physiochemical characterization of the enzyme reveled the enzyme hada wide pH stability range 4-7 with optimum pH 5 while the temperature stability study revealed the enzyme was stable up to 60°C while the optimumtemperature of the purified enzyme was 45°C. The enzyme was strongly inhibited by Hg2+ and Ag2+ at 1 mM concentration while Mg ionsenhanced the enzyme activity at the same concentration. The kinetic study of the enzyme showed Km and V of the enzyme 5.2 mM/ml and 8.6 U/ml,respectively.Conclusion: The wide pH and temperature stability range show its suitability toward industrial application.maxKeywords: α-glucosidase, Hyophilla nymaniana (Fleish.) Menzel. gel filtration, Diethylaminoethyl sephadex column chromatography

Fostering quality teachers in teacher education in the context of internationalization: tasks ahead

Education being a process of strengthening human resources, its quality assumes special significance within the larger framework of personal, social and national development. The educational system of the 21st century must be oriented toward creating conditions that allow school students to act and learn freely in productive collaboration with their teachers, and also with their parents and other members of their community, local and global. Government of India's Ministry of Education in its report said “the most important factor in the contemplated educational reconstruction is the teacher, his personal qualities, educational qualifications, professional training and his place in school and community. Although, India is developing democratic country, to bring qualities in all aspects of teacher education in the light of internationalization, matter of serious concerned and needs immediate attention so that we may get such teachers who not only will possess world class knowledge but also right attitude to work and live with open mindedness

IN VITRO CULTURE OF MOSS BRYUM CORONATUM SCHWAEGR.(BRYACEAE) AND IT'S PHYTOCHEMICAL ANALYSIS

Objective: The purpose of the present investigation was to establish in vitro conditions for moss Bryum coronatum Schwaegr. And to carry out preliminary phytochemical screening of B. coronatum leaf extracts in different solvents. Methods: Fresh unopened, mature capsules were used as explant and surface sterilization of spores bearing capsule with different concentration of sodium hypochlorite (0.5, 1, 2, 4 and 8%) with different time duration. The Mu­rashige and Skoog (MS) medium that contains different concentration(full,1/2, 1/4th, 1/8th strength) with different concentration of sucrose were used for culture this moss. Phytochemical screening were carried out using ethanol, methanol and ethyl acetate leaf extract of B. coronatum to identify various constitutes using the standard procedures. Results: Surface sterilization of spores of this moss was most effective in 4% commercial bleach for 1 min sterilization. The optimum condition for germination of spores and for proper growth of gametophytes B. coronatum on MS/4 medium strength with sucrose (1.5%), at pH 5.8 and temperature 22±2ºC with 16/8h: light/dark condition. Phytochemical analyses revealed the presence of alkaloids, terpenoids and saponins in all extracts. Conclusion: Four percentage NaOCl aqueous solutions are better for surface sterilization of moss sporophytes. MS/4 medium with 1.5% sucrose found the best medium for spore germination. Solvents extracts showed presence of alkaloids, terpenoids and saponins in all extracts

A novel approach in non-surgical management of tubal ectopic: combination of minimally invasive technique under ultrasound guidance with systemic methotrexate based on initial beta-HCG levels

Background: Single dose methotrexate is the most preferred method of non-surgical management of unruptured tubal ectopic. A 2-dose regimen is suggested to treat tubal ectopic with higher trophoblastic cell load. Minimally invasive technique of ultrasound guided intracardiac KCL instillation along with systemic methotrexate has been in use even for live ectopic pregnancy. Objective of the study was to evaluate the success rate of single dose regimen of MTX (Methotrexate), 2-dose regimen of MTX and ultrasound guided instillation of intracardiac KCl in three different cohort of unruptured tubal ectopic pregnancy with an attempt to increase success of non-surgical management.Methods: Fifty-eight women with unruptured tubal ectopic pregnancy were assigned to treatment protocols according to the initial β-HCG levels and presence/absence of FCA (fetal cardiac activity). Group 1: presence of FCA in the tubal ectopic; Group 2: initial β-HCG ≤5000 IU/ml; Group 3:  initial β-HCG ≥5000 IU/ml without FCA. Women in group 1 were treated with ultrasound guided instillation of intracardiac KCl combined with systemic MTX. While women in group 2 were administered single dose regimen of MTX and group 3 received 2-dose regimen of MTX.Results: Overall success rate of non-surgical management was 89.3% across all groups. Success rate in Group 1 was 78.6%. Success rate was 93.1% in group 2 while 92.3% in group 3. Rupture rate was 1.7% in the present study.Conclusions: For non-surgical management categorizing and treating is an option with good result. Women with presence of cardiac activity can opt for non-surgical option with likely resolution in 78% cases

Effect of lisinopril and perindopril on serum lipid profile in Albino rabbits

Background: Hypertension with dislipidemia is becoming a common morbidity, since ACE inhibitors are the first line of antihypertensive drugs so present study was undertaken with the aim to evaluate the possible effects of ACE inhibitor on lipid profile in albino rabbits.Methods: The study was conducted in the Department of Pharmacology and Therapeutics, GSVM Medical College, Kanpur. Rabbits were divided into 2 groups with 6 in each group. Rabbits of Group I was given Lisinopril in dose of 0.25mg/kg and of group II was given Perindopril in dose of 0.20mg/kg for a period of 6 weeks. Lipid profile estimation (Serum Total cholesterol, serum HDL, serum LDL, serum Triglycerides and serum VLDL) was done at day 0, 7, 21 and 45 respectively.Results: After analysis Rabbits of group-I (Lisinopril) showed 3.1% decrease in serum cholesterol level at 45th day (P0.05). Serum LDL level decreases by 4.4% and 8.6% at day 21 and 45 respectively (P<0.001). There was no significant change in Serum VLDL level. Rabbits of group- II (Perindopril) showed decreased total cholesterol levels by 2.6% (P<0.05). There was an increase in HDL level by 6.8 % at day 45(P<.05). Triglycerides and VLDL levels were not significantly altered while serum LDL level decreases by 6.7% at day 45 (P<0.01).Conclusions: From our study it was concluded that Lisinopril had a favourable effect on serum lipid profile by decreasing total cholesterol, increasing serum HDL level. It may increase triglycerides, decrease LDL. Perindopril increase serum HDL and decreases LDL, there is no significant change in cholesterol, TG and VLDL levels

Evaluation of mineral status in hypothyroidism in a tertiary care centre

Background: Hypothyroidism is known to be the commonest form of endocrine disorders and has been linked with disturbances in various minerals metabolism. Calcium, phosphorus and magnesium and trace element zinc are required for many enzymes in various metabolic pathways which are directly or indirectly regulated by thyroid hormones. Aim and objectives of the study was to estimate serum zinc, calcium, magnesium and phosphorus in hypothyroid patients, with the objectives to evaluate any relationship with TSH and to compare them with euthyroid controls.Methods: The analytical cross-sectional study included 50 hypothyroid subjects with TSH levels >4.5 mcg IU/mL and 50 euthyroid subjects of 20-50 years in RMCH, Bareilly. TSH was estimated by ECLIA, serum calcium and phosphorus were estimated by autoanalyzer and serum zinc & magnesium by the kit method using semi autoanalyzer. All the biochemical parameters were expressed as median with Interquartile Range (IQR). Mann-Whitney test was applied to compare the parameters of cases and control. Spearman’s rank correlation coefficient 2-tailed was used to correlate the parameters among the cases.Results: A significantly decreased level of serum calcium and increased level of serum magnesium and phosphorus were observed in hypothyroid cases. A significant negative correlation between TSH and serum calcium while a significant positive correlation of serum magnesium and phosphorus with TSH was observed.Conclusions: The indexed study indicates the significant effect of overt or subclinical hypothyroidism over the mineral status of the body which may have inconsistent effect over the various metabolism and enzymes and thereby clinical manifestations

Diabetes-Driven Dilemma: Tackling The Rise of Melioidosis in India

Melioidosis is a potentially fatal infectious disease that requires an extended period of treatment for complete resolution of the infection. It can lead to chronic and severe infections, and it is more common in diabetic patients. Melioidosis is also a significant concern in India primarily because its chronic nature, potential for dissemination, extended treatment requirements, and the risk of relapse lead to its resemblance to tuberculosis. This case series included osteomyelitis patient presented in emergency with sepsis MODS, disseminated melioidosis patient with systemic involvement including spleen, kidney and lungs, skin abscess at more than one site, urosepsis, splenic abscess, Melioidotic arthritis. Many of these patients had altered blood sugar levels, and in 3 cases, individuals were even diagnosed with diabetes during their episode of melioidosis the treatment duration generally involved an 8-week course of intravenous antibiotics. However, oral medications may need to be continued for several months if necessary for complete recovery. &nbsp

Anti-nociceptive effect of seed extract of Acacia tortilis in rodents

Background: Management of pain is a primary clinical concern for any pathology in medical field. Addiction liability of opioids and troublesome gastrointestinal side effects of NSAIDs   leads to intensive research for compound with lesser side effects.The aim of the study to evaluate the anti-nociceptive activity of Acacia Tortilis Seed Extract (ATE) in experimental animals.Methods: First of all, animals were randomly allocated into four groups of six animals each. In acetic acid induced writhing test model, Group I (NC) served as vehicle control received saline/Tween 80 0.1%, 10ml/kg BW orally, group II (ATE-100) and III (ATE-200) received ATE in dose of 100 and 200mg/kg BW orally respectively and group IV received the standard drug diclofenac sodium in dose of 50 mg/kg BW orally. Group I to IV were same in rest of three experimental models. One additional group of standard drugs (group V) morphine sulfate in dose of 5 mg/kg BW subcutaneously (SC) was allocated for screening method hot plate and tail flick tests.  In Formalin induced paw licking test, three additional groups (group V) morphine sulfate in dose of 5mg/kg BW SC, group VI- morphine+naloxone (5mg/kg SC +2mg/kg intra-peritoneally (IP) and group VII - ATE+ naloxone (200mg/kg BW orally +2mg/kg BW IP) were also made.Results: The ATE when administered orally in dose of 100 and 200mg/ kg body weight (BW), produced significant analgesic activity (P <0.01) in acetic acid induced writhing syndrome and late phase of formalin test. In the hot plate test in mice and tail flick test in rats, ATE in same doses also showed significant analgesic activity (P <0.05) which is almost equally efficacious to standard drug diclofenac sodium (50mg/kg BW orally) but far less efficacious than morphine sulfate (5mg/kg BW subcutaneous).ATE (200mg/Kg BW orally) activity did not blocked by naloxone (2mg/kg intra-peritoneal).Conclusions: ATE possesss significant anti-nociceptive activity as evidenced in all the animal models of nociception. It might exert its effect through the peripheral mechanism of analgesic action possibly by interference in biosynthesis, release and/or action of prostaglandins and leukotrienes