A Study of Diasporic Divulgencies in the Works of Rohinton Mistry

Diaspora fiction deals with the issues of two different social milieus having discriminating margins, disintegration or combination of cultures and is also lingers over the related feelings such as nostalgia, loneliness, alienation, existential rootlessness, homelessness, quest of identity, protest, assertions and questioning etc. Rohinton Mistry is one such writer who is well known for his depiction of these psycho-sociological problems by the emigrants and immigrants. Rohinton belongs to the Parsi Zoroastrain religious minority while residing in Brampton, Ontario, Canada. Being himself a victim, most of his works are concerned to scrutinize the complexities of contemporary rootlessness and alienated identities of the Parsi community he describes. While in India these Parsis are called “Ghatis” and when they move towards the United States and Canada, they are called “Pakis”, and Mistry considers both of them to be dehumanizing. He raises voice against the victimization of these emigrants and immigrants and highlights their struggle also

Deciphering the mechanism and function of stage-specific protein association with the membrane cytoskeleton of Toxoplasma gondii:

Thesis advisor: Marc-Jan GubbelsApicomplexan parasites like Toxoplasma gondii have a complex life cycle comprising of transitions between different hosts, different organ systems and between the extracellular and intracellular milieu. The parasite must thus adjust itself and its cellular processes in accordance with its environment. In this dissertation, I have focused on such stage specific behaviors of three distinct intermediate filament-like proteins as well as a glycolytic enzyme, glyceraldehyde-3-phosphate dehydrogenase 1 (GAPDH1). These proteins relocate from the cytosol to the unique cortical membrane skeleton of non-dividing parasites. The intermediate filament-like proteins IMC7, 12 and 14, localize exclusively to the mature cytoskeleton. One model of function was that these proteins differentially stabilized mother and budding daughter cytoskeletons in the division process, but we ruled out this role for the individual proteins, as they are not essential for the lytic cycle of the parasite. However, we determined that IMC7 and IMC14 are contributing to the maintenance of rigidity of the cytoskeleton under osmotic stress conditions in extracellular parasites. In addition, IMC14 is critical in cell cycle progression as its depletion results in the formation of multiple daughters per division round. When the parasite egresses from the host cell, glycolytic enzyme GAPDH1 translocates to the cortex. The functional role of GAPDH1 in the parasite and the mechanism of its cortical translocation are deciphered based on the 2.25Å resolution crystal structure of the GAPDH1 holoenzyme in a quaternary complex. These studies identified that GAPDH1’s enzymatic function is essential for intracellular replication but we confirmed the previous reports that glycolysis is not strictly essential in presence of excess L-glutamine. We identify, for the first time, S-loop phosphorylation as a novel, critical regulator of enzymatic activity that is consistent with the notion that the S-loop is critical for cofactor binding, allosteric activation and oligomerization. We show that neither enzymatic activity nor phosphorylation state correlate with the ability to translocate to the cortex. However, we demonstrate that association of GAPDH1 with the cortex is mediated by Cysteine 3 in the N-terminus, likely by palmitoylation. Overall, glycolysis and cortical translocation are functionally decoupled by post-translational modifications. Collectively, the discoveries made in this dissertation reveal unprecedented detail in mechanism and function of cortical protein translocation and thereby identifying new drug targets.Thesis (PhD) — Boston College, 2017.Submitted to: Boston College. Graduate School of Arts and Sciences.Discipline: Biology

Identification and characterization of novel splice variants of the human EPM2A gene mutated in Lafora progressive myoclonus epilepsy

The EPM2A gene, defective in the fatal neurodegenerative disorder Lafora disease (LD), is known to encode two distinct proteins by differential splicing; a phosphatase active cytoplasmic isoform and a phosphatase inactive nuclear isoform. We report here the identification of three novel EPM2A splice variants with potential to code for five distinct proteins in alternate reading frames. These novel isoforms, when ectopically expressed in cell lines, show distinct subcellular localization, interact with and serve as substrates of malin ubiquitin ligase—the second protein defective in LD. Two phosphatase active isoforms interact to form a heterodimeric complex that is inactive as a phosphatase in vitro, suggesting an antagonistic function for laforin isoforms if expressed endogenously in significant amounts in human tissues. Thus alternative splicing could possibly be one of the mechanisms by which EPM2A may regulate the cellular functions of the proteins it codes for

A comparative study on post-operative analgesic effect by intrathecal midazolam and neostigmine with control group

Background: Pain happens to be the most common suffering during postoperative period, which is not generally effectively treated. There is good evidence in literature that addition of midazolam to spinal bupivacaine improved postoperative analgesia when compared to spinal bupivacaine alone. Neostigmine represents a novel approach to providing analgesia. Recent studies showed that intrathecal administration of various doses of neostigmine produces analgesia without neurotoxicity. The present study was undertaken to evaluate analgesic effects of intrathecal Midazolam and neostigmine.Methods: The present study was carried out in the department of anaesthesiology, CCM medical college, Durg Chhattisgarh, India during study period August 2015 to July 2016. The study comprised of 60 patients undergoing surgery of lower abdomen below umbilicus (T10) and lower limbs. Patients of age Group between 20-60 years of age of either sex of ASA group I and II were included in the study. Pre-anesthetic evaluation was done prior to surgery. The patients were randomly divided into 3 groups of 20 patients each. Data was compiled in MS excel and checked for its completeness and correctness, then it was analyzed.Results: Mean age in Group I was 39.3+1.5 years. in Group II was 37.8±11.7 years, in Group III was 42.2±13.7 years. In group I maximum 14 patients (70%) had analgesia of less than 4 hours. Mean duration of analgesia was 3.73±0.87 hours. In group II maximum 18 patients (90%) had analgesia 4-8 hours. The mean duration of analgesia was 6.34±1.28 hours. In group III 10 patients (50%) had analgesia of 4-8 hours and 10 patients (50%) had analgesia of 8-12 hours. The mean duration was 8.35±1.36. The difference in VAS score in group in group I and group III is significant. There was no statistically significant change in systolic blood pressure, diastolic blood pressure, Pulse rate & respiratory rate attributable to intrathecal Midazolam and neostigmine.Conclusions: Addition of preservative free midazolam to inteathecal bupivacaine prolongs duration of effective analgesia as compared to bupivacaine alone without any side effects. Addition of preservative free neostigmine to intrathecal bupivacaine prolongs duration of effective analgesia and sensory and motor block without any significant side effects

A Comprehensive Review on Anti-Cancer Properties of Amaranthus viridis

Amaranthus Viridis L. belongs to the Family (Amaranthaceae) commonly known as “Chowlai” which a common name. A. Viridis contains several compounds like Quercetin, Kaempferol, Hydroxycinnamic acids (HCs) (coumaric acid, ferulic acid, sinapic acid, caffeic acid, chlorogenic acid, rosmarinic acid), Syringic acid (SA), Rutin, Vitexin, Vanillic acid, etc . In search of new activities and chemical entities, phytochemical screening of the extract from leaves of A. Viridis L. indicates the presence of biologically active constituents saponins, tannins, phenols, flavonoids, alkaloids, cardiac glycoside, steroids, and triterpenoids. Quercetin is the aglycone form of several other flavonoid glycosides, Kaempferol (3,4′,5,7- tetrahydroxyflavone) is a natural flavonol, a type of flavonoid, Syringic acid (SA) is a phenolic compound of natural origin. Syringic acid (SA) is a phenolic compound which obtained from natural origin. SA is an excellent compound to be used as a therapeutic agent in various diseases (diabetes, CVDs, cancer, cerebral ischemia, neuro and liver damage) and possesses anti-oxidant, antimicrobial, anti-inflammatory, and antiendotoxic activities. Vitexin (apigenin-8-C-glucoside) has also shows the wide range of pharmacological effects, including but not limited to anti-oxidant, anti-cancer, anti-inflammatory, and neuroprotective effects. Vanillic acid shows the anti-cancer activity

Scavenging and metal chelating potential of Carthamus tinctorius L. extracts

Carthamus tinctorius leaves were extracted with methanol and distilled water. The extracts were evaluated for their potential free radical scavenging capacity using four different in vitro methods (DPPH, metal chelation, radical removal and hydrogen peroxide scavenging methods). The total phenolic content obtained for aqueous (112. 2±1.708 GAE mg/g) and for methanolic extract (89.66±2.00 GAE mg/g). In DPPH, IC50 values was found to be 176.66±2.08 and 278.33±1.52 and 310.33±1.52 for the ascorbic acid, aqueous and methanolic extract respectively. In superoxide radical scavenging IC50 values are 381.27±1.43, 544.42±2 and 606.78±3.02 µg/ml for the ascorbic acid, aqueous and methanolic extract respectively. In the metal chelating activity, IC50 values are 385.94±3.00, 337±1 and 487±0.984 µg/ml for the EDTA, aqueous extract and methanolic extract respectively. In hydrogen peroxide scavenging, IC50 values were 261±1, 278±3.52 and 370±1 µg/ml for the ascorbic acid, aqueous extract and methanolic leaf extract of Carthamus tinctorius respectively. The correlation suggests that phenolic compounds are responsible for the antioxidant activities of leaves

Comparative study of various tocolytics in preterm labour

Background: Preterm birth is one of the major factors responsible for neonatal mortality and morbidity. In this study, we have to see the role of various tocolytics in preventing preterm labour.Methods: The observational study was conducted on 200 patients admitted in Upper India Sugar Exchange Maternity Hospital, Kanpur.Results: In our study calcium channel blocker were associated with statistically and clinically significantly better neonatal outcome and fewer maternal side effects than any other tocolytic. So calcium channel blocker would be preferred first line tocolytic with regard to several important outcomes.Conclusions: Preterm birth continued to be problem for obstetrician. Administration of short term tocolytic agents can prolong pregnancy for women in pre-term labor. Prolonging pregnancy may have benefits because it allows for other proven interventions, such as antenatal corticosteroid administration to be accomplished. The reviews proven an overview currently utilize tocolytic agents and the evidence of demonstrating their efficacy for prolonging pregnancy by at least 48 hours

Toxicity assessment of the alcoholic leaves extract of Reinwardtia indica

The present study aimed to evaluate the safety of the alcoholic leaves extract of Reinwardtia indica in Charles foster rats through an acute and sub-acute oral administration.For assessment of acute oral toxicity test, ratswere orally treated with single dose of the alcoholic leaves extract of Reinwardtia indica at the doses of 50, 250, 500, 1000 2000 and 5000 mg/kg. In sub-acute toxicity study, using the OECD guidelines no. 407, the extract was administered at the doses of 50, 250, 500, 1000, 2000 mg/kg/day for 28 consecutive days and at the dose of 2000 mg/kg satellite group also used for 6 weeks.In acute toxicity above mentioned doses neither showed mortality nor exterior signs of toxicity. In sub-acute, study no significant changes found in haematological and biochemical level ofthe treated rat after 14 days and 28 days in comparison to control. The histopathology of rat brain, kidney, liver, and heart also showed the no cellular changes after extract treated rat.The alcoholic leaves extract of Reinwardtia indica was found non-toxic in single drug dose administration up to 5000 mg/kg (acute study) and in sub-acute administration up to 2000 mg/kg

Assessment of total phenolic content and antioxidant potentiality of selected Indian folk medicinal plants by spectrophotometric method

Natural antioxidant capacity of five important folk medicinal plants measured in vitro. Total phenolic content (TPC), flavonoid content (FC) and free radical scavenging capacity of ethanolic, methanolic and aqueous leaf extracts of Lippia alba (LA), Annona squamosa (AS), Hyptis suaveolens (HS), Commiphora wightii (CW) and Milletia pinnata (MP) was assessed using spectrophotometric method. Folin ciocalteu and aluminium chloride method employed to optimise TPC and FC. Free radical scavenging potentiality of leaf extracts was assessed using Ferrous ion chelation (FIC), 2, 2'-diphenyl-1-picrylhydrazyl (DPPH•) scavenging, Hydroxyl (OH•) radical scavenging (HRS) and Superoxide (O- 2) radical scavenging (SRS) methods. Results revealed that the TPC (96.22±5.85 to 519.23±34.90 ?g GAE/gm dry weight) were found significant in aqueous extracts from all the plants except AS (p<0.05). For FC (?g QCE/gm dry weight), ethanol was found optimum for LA (463.94±6.49), CW (289.99±2.70) and MP (347.47±4.50) whereas, aqueous was found more appropriate for rest two plants were found significant instead of ethanol and methanol (all p<0.05). The lowest IC50 (?g/ml) were recorded from A. squamosa (27.72±8.95), H. suaveolens (27.78±0.88), C. wightii (27.18±0.16) and M. pinnata (27.30±0.03). All plants have reflected a high antioxidant capacity; however, the highest antioxidant activity was reported from ethanolic extract of H. suaveolens followed by L. alba, A. squamosa, C. wightii and M. pinnata. Hence, these studies show that all folk medicinal plants contain potential antioxidant bioactive compounds

Advances in Gene Ontology Utilization Improve Statistical Power of Annotation Enrichment

Gene-annotation enrichment is a common method for utilizing ontology-based annotations in gene and gene-product centric knowledgebases. Effective utilization of these annotations requires inferring semantic linkages by tracing paths through edges in the ontological graph, referred to as relations. However, some relations are semantically problematic with respect to scope, necessitating their omission or modification lest erroneous term mappings occur. To address these issues, we created the Gene Ontology Categorization Suite, or GOcats—a novel tool that organizes the Gene Ontology into subgraphs representing user-defined concepts, while ensuring that all appropriate relations are congruent with respect to scoping semantics. Here, we demonstrate the improvements in annotation enrichment by re-interpreting edges that would otherwise be omitted by traditional ancestor path-tracing methods. Specifically, we show that GOcats’ unique handling of relations improves enrichment over conventional methods in the analysis of two different gene-expression datasets: a breast cancer microarray dataset and several horse cartilage development RNAseq datasets. With the breast cancer microarray dataset, we observed significant improvement (one-sided binomial test p-value = 1.86E-25) in 182 of 217 significantly enriched GO terms identified from the conventional path traversal method when GOcats’ path traversal was used. We also found new significantly enriched terms using GOcats, whose biological relevancy has been experimentally demonstrated elsewhere. Likewise, on the horse RNAseq datasets, we observed a significant improvement in GO term enrichment when using GOcat’s path traversal: one-sided binomial test p-values range from 1.32E-03 to 2.58E-44