Mechanisms involved in regulation of MHC class I molecules in murine embryonic stem cells

Major histocompatibility complex (MHC) is at the center of immune responses that support survival, fitness and adaptation of mammalian species to the environment. These molecules are not only crucial for adaptive and innate immune responses against microorganisms and cancer cells but also play an important role in reproduction process and development of embryo during the preimplantation period. In the present study, we use murine embryonic stem cells (ESCs) as model to dissect the molecular mechanism involved in the regulation of MHC class I molecules during differentiation in vitro. MHC class I molecules are expressed at very low levels on murine ESCs and they are not induced by the immunomodulatory cytokine interferon gamma (IFN) despite the presence of IFN receptors on their cell surface. First, we showed that removal of leukemia inhibitory factor (LIF), a standard component of murine ES cell culture media required for the maintenance of a pluripotent state, did not result in up regulation of MHC class I expression in murine ESCs, presumably due to incomplete inactivation under these experimental conditions of STAT3 signaling pathway, which is used by LIF. However, the addition of LIF to differentiated cells in embryoid bodies strongly suppressed the expression of these molecules. Down regulation of STAT3 in undifferentiated ESCs cultured in the presence of LIF significantly increased the expression of MHC class I molecules and this was further enhanced by IFN treatment. Flow cytometric analysis revealed that STAT1 is phosphorylated by IFN in STAT3 knockdown (KD) ESCs, whereas there was only weak or no phophorylation detected in mock siRNA 647-treated ESCs exposed to IFN. Luciferase reporter assay also indicated that GAS promoter responded to IFN much strongly in STAT3-depleted ESCs than in intact cells, suggesting that ESCs do not respond to IFN at least partially due to inhibitory effects of STAT3-signaling components on STAT1-phosphorylation. Moreover, the down regulation of suppressor of cytokine signaling 3 (SOCS3) in STAT3 KD ESCs increases the possible regulation of STAT1 phosphorylation by SOCS3. No effect in MHC class I molecules induction was observed in STAT3 KD ES-derived cardiomyocytes (ESCMs) indicating the differential regulation of these molecules during the course of differentiation from undifferentiated stage (ESCs) to differentiated stage (ESCMs). An additional mechanism by which STAT3 regulates MHC class I expression may involve epigenetic modification of MHC class I gene expression since Dnmt knockout (KO) murine ESCs showed upregulation of MHC class I molecules. Chromatin modifying gene Eed1 but not Dnmt1 and Jmjd1 was significantly downregulated in STAT3 KD murine ESCs. Additionally, murine ESCs showed increased MHC class I expression and enhanced response to IFN after treatment with the DNA-methyltransferase inhibitor 2,5-azacytidine and histone deacetylase inhibitor Trichostatin A. Modulation of MHC class I expression by STAT3 KD in ESCs reduced their lysis by activated syngeneic NK cells and increased their lysis by cytotoxic T cells compared to mock siRNA 647-treated ESCs. These data indicate that STAT3 pathway plays a dual role in modulating the MHC class I expression in ESCs. Interfering with the inhibitory pathways that suppress MHC class I expression in pluripotent ESCs may help to control teratoma formation from contaminating ESCs in therapeutic cell transplants and may also help to eradicate cancer cells and virus-infected cells that are known to frequently evade immune recognition by down regulating the MHC class I expression

Investigations on Properties of Glass Fibre Reinforced Polymer Composite

The aim of present study is to investigate the water absorption, mechanical and thermal properties of glass fibre reinforced polymer composites (GFRPCs). Multi layers of  woven glass fibres are reinforced into epoxy matrix to prepare the composites by hand lay-up technique. Water absorption properties are investigated in terms of percentage of water uptake, and sorption, diffusion and permeability coefficients. On the other hand, mechanical properties are investigated in terms of tensile, flexural and impact test as per ASTM standards. Moreover, thermal properties are investigated using thermogravimetric analysis (TGA) and dynamic mechanical analysis (DMA). The results have been shown that water absorption, mechanical and thermal properties are increased with increase in numbers of layers of woven glass fibres in epoxy matrix

Biochemical Evaluation of Forage Sorghum for Stress Tolerance

Abiotic stresses are the major limiting factors in plant growth. With continuous increment in scarcity of water and increased salinization of soil and water, it is estimated that more than 50% of all arable lands will be affected by salinity and drought by 2050. Plants are often exposed to both, soil and atmospheric water deficit during their life cycle. The frequency and intensity of droughts is increasing as a result of global climate change. Understanding how plants respond to water stress is thus crucial for the estimation of impacts of climate change on crop productivity and ecosystem functioning. The knowledge about the mechanism adapted by plant to respond to drought, salt and co-occurring stresses can play an important role in stabilizing crop performance under drought and saline conditions. Sorghum (Sorghum bicolor L.) is an important crop in many parts of the world. It is utilized as food, fodder and several industrial purposes. In general, sorghum is known to be more tolerant to any stresses including heat, drought, salinity and flooding

Neural Network Based Indexing and Recognition of Power Quality Disturbances

Power quality (PQ) analysis has become imperative for utilities as well as for consumers due to huge cost burden of poor power quality. Accurate recognition of PQ disturbances is still a challenging task, whereas methods for its indexing are not much investigated yet. This paper expounds a system, which includes generation of unique patterns called signatures of various PQ disturbances using continuous wavelet transform (CWT) and recognition of these signatures using feed-forward neural network. It is also corroborated that the size of signatures of PQ disturbances are proportional to its magnitude, so this feature of the signature is used for indexing the level of PQ disturbance in three sub-classes’ viz. high, medium, and low. Further, the effect of number of neurons used by neural network on the performance of recognition is also analyzed. Almost 100% accuracy of recognition substantiates the effectiveness of the proposed system. 

Effect of Stacking Sequence on Flexural and Dynamic Mechanical Properties of Hybrid Sisal/Glass Polyester Composite

In present study, flexural properties in terms of break load, percentage elongation, flexural strength and flexural modulus, and dynamic mechanical analysis (DMA) in terms of storage modulus (), loss modulus (), damping , glass transition temperature  and effectiveness constant of reinforcement  of hybrid sisal/glass fibre reinforced polyester composite are investigated. Polyester based hybrid composites are prepared by Hand lay-up technique followed by static compression having constant 25 wt.% of fibre content  with various stacking sequences.  A significant improvement in flexural properties of sisal fibre reinforced polyester composite is observed by incorporation of glass fibre.  In addition, the stacking sequence has great influences on flexural and dynamic mechanical properties of hybrid composites

Study of epidemiological aspects and hormone receptor status of meningiomas

Background: Meningiomas account for about a third of all central nervous system tumours worldwide. Though very common, quite less is known about its epidemiology. This study aims to establish the epidemiological parameters and hormone receptor status (Progesterone Receptor-PR) involved in the development of Meningiomas.Methods: This observational study included 50 patients. Epidemiological parameters studied included age, sex, symptoms, history of hormone intake, smoking, recurrence, family history, history of other hormone related tumours and radiological assessment of tumour site. Surgical samples were grossed and typed according to the WHO standards. Immunohistochemical staining was done using PR to establish the role of hormonal receptors in the development of meningiomas.Results: The mean age was 46.84±13.54 years. The ratio of male and female (Male:Female) was 1.0:2.3. 48.5% of females had history of hormonal pill intake and 28.6% had hormone related tumours, of which fibroid was most common. Amongst the sites involved cerebral convexity was most common (56%). Chi-square (χ2) test showed that there was a significant association between histological grade and PR expression of the patients (p=0.0002).Conclusions: Positivity for hormone receptors like PR, increased intake of hormonal pills by females and association of meningioma with hormone related tumours indicates that hormonal milieu plays a significant role in the growth of meningiomasχχ. This could thus provide an insight to the pathogenesis of meningiomas. In addition, mifepristone, an anti-progestin could be a player in the medical management of meningiomas

Synthesis, Characterization and Anti-Microbial Activity of Indole Derivatives

Indoles are probably the most widely distributed heterocyclic compound in nature. Tryptophan and essential amino acid as such is constituent of most proteins. Starting materials were identified by physical, chromatographic and spectral analysis. For substituted isonitroso acetanilide 3.6 gm (0.05M) of chloral hydrate and 48 ml of purified water was taken in it. Then 44 gm of crystallized anhydrous sodium sulfate was added in it and a solution of substituted aniline (0.05 M) in 12 ml of water with 1.7 ml (0.052M) of concentrated hydrochloric acid was added to dissolve the amine, and finally, a solution of 4.5gm (0.158M) of hydroxylamine hydrochloride in 20 ml of water.for preparation of  substituted isatin from substituted isonitroso acetanilide 32.5 ml of concentrated sulfuric acid was warmed upto 50°C in a 100 ml round bottom flask with continuous stirring, and 7.5 gram of (0.046 M) of dry substituted isonitroso acetanilide was added to such a rate that to keep the temperature 60-70 but not higher. All synthesized final products were screened for in vitro antibacterial activity [ 13-19, 20-22] against four bacterial strains, namely Staphylococcus aureus (MTCC 96), Staphylococcus pyogenus, Pseudomonas aeruginosa (MTCC 1688), Escherichia coli (MTCC 443) and two fungal strains, namely Candida albicans (MTCC 227) and Aspergilla niger (MTCC 282). in-vitro antimicrobial activity with the zone Inhibition in mm 24±2 and activity index 0.89, against Staphylococcus aureus, 22±2 and 0.85 against Staphylococcus pyogenes, 26±2 and 0.96 against Pseudomonas aeruginos, 25±3 and 0.86 against Escherichia coli and two fungal strains shown 26±4 and 0.81 against Candida albicans and 14±2 & 0.88 against Aspergilla niger respectively. Keywords: Indole, Isatin, Antibacterial activity, Staphylococcus aureus

Synthesis, Characterization and Anthelmentic Activity of Indole Derivatives

Indole is a planar molecule with a conjugated system of 10 p electrons. It exists in resonance form with resonance energy of 47-49 K cal/mole. It is a very weak base with Pka value 3.63. In structure a, b, and d the benzenoid 6-p system is preserved. The chemical structures of the synthesized compounds were established on the basis of physical, chemical, analytical data. The purification of the compounds was carried by purification methods like recrystallization. Physical constant like melting point, boiling point etc, of the new compounds were determined. All the intermediates and final synthesized products were inspected visually for physical appearance. It was physically characterized on the basis of organoleptic properties like color, odor and taste. This determination was obtained using a digital capillary melting point apparatus (Cambell Electronics, Bombay, India) by capillary fusion method. All the synthesized materials were further identified and confirmed by Thin Layer Chromatographic (TLC). UV/Visible spectra enables us o study the absorption pattern of the molecule and determination of lmax which is useful for the quantitative estimation of the compound. The IR spectrum of all the synthesized materials was recorded, which showed stretching and bending vibration levels of molecules in potassium bromide pellet by FTIR Spectrophotometer. The synthesized compounds were screened for Anthelmintic activity by using Mathew et al method and Indian adult earthworms (Pheretima Posthuma). All substituted quinoxaline compounds have been screened for their anthelmentic activity. From the screening results it was observed that the presence of electron withdrawing group made the substituted quinoxaline compounds to exhibit moderate to significant anthelmentic activity in comparison to standard drug albendazole. Compound QX1 and QX5 exhibited promising anthelmentic activity. However other two compounds (QX2 & QX4) of the series also exhibited moderate to weak activity against the Pheritma phosthuma. Keywords: Pheritma phosthuma, Indole, Anthelmentic activity

Psychosocial status and quality of life of adolescent girls in Karnataka, India

Background: This study was conducted with the objective to assess the psychosocial status and quality of life (QOL) of adolescent girls in Karnataka, India.Methods: This was a cross sectional community based study which was conducted on 400 adolescent girls each in rural (Bellary district) and urban (Bangalore district) areas of Karnataka, India. WHO’s ‘HEEADSSS’ questionnaire and ‘WHOQOL-BREF’ tool have been used to assess psychosocial status and quality of life of adolescent girls, respectively.Results: It was observed that nearly 5% girls were at severe and very severe risk of developing psychosocial abnormalities in both rural and urban study area. The mean QOL score was highest for social relations (7102±21.6) and was minimum for physical domain (49.59±12.63).Conclusions: This calls for urgent community based interventions directed to adolescents and their families having higher vulnerability for psychosocial abnormalities and poor quality of life

Measurement of Yearly Wastage in Elementary Education

The problem of wastage in Elementary Education System is becoming gradually very serious, across the world. Various methods have been proposed by researchers to measure real wastage in an Indian educational system, which seem to be inadequate because of multiple reasons. One of the main reasons is the occurrence of different type of wastages in the elementary education system. Further, there no reliable and consistent database, of educational statistics, that are available. In this paper, we wish to propose a method for measuring the real wastage by using the appropriate statistical technique of sampling