Importance and Challenges of International Service-Learning

Service-learning is an important component of a college education as it helps students demonstrate a positive impact on their community using their classroom knowledge. Through business writing, a Purdue English course, we were able to learn about how to market effectively to a college audience and were able to implement these learnings in our partnership with Code for Nepal. Code for Nepal is an organization that works to improve the digital literacy of women and other minority groups within Nepal. Their most impactful work was creating a document encompassing key information regarding food, water, and shelter after the 2015 earthquake. As part of our work with them, we hosted a Coffee and Donuts event to raise donor and volunteer engagement across college campuses in the United States. The skills developed through this course and partnership were invaluable, and I have been able to implement many of them to host other student activity-related events on campus. Not only do service-learning projects make a positive impact on the organization that we partner with, but they also allow students to further refine the skills learned in the classroom. Through this article, I would like to share more about the skills developed in business writing at Purdue, how we worked alongside Code for Nepal, as well as the impact it has made on the rest of my college experience

ER stress mediated effects on plasma membrane cholesterol and nitric oxide bioavailability

Endothelial dysfunction is due in part to the decrease in the biosynthesis and the bioavailability of nitric oxide (NO) in the endothelial cell layer. The chronic exposure of blood vessels to cardiovascular risk factors such as LDL-cholesterol, free fatty acids, homocysteine and conditions of hyperglycemia can give rise to endothelial dysfunction. Many of these same risk factors have also been shown to induce endoplasmic reticulum (ER) stress, in endothelial cells. However, the potential links between endothelial dysfunction and ER-stress have not been clearly established. The present study was undertaken with two objectives. Objective 1 was to determine how increased plasma membrane cholesterol content can affect NO diffusion, dynamics and signalling. Objective 2 was to determine whether the unfolded protein response mediated by ER stress can lead to increase in plasma membrane cholesterol in endothelial cells, how ER stress leads to increase in plasma membrane cholesterol and whether increase in plasma membrane cholesterol can influence eNOS activity and localization in the endothelial cells. Objective 1 was carried out by taking Normal Human Fibroblasts (NHF1) and sterol transport-defective Niemann Pick type C1(NPC1) fibroblasts which exhibit increase plasma membrane cholesterol content. NPC1 fibroblats showed decreased activation of both intracellular sGC and VASP (Ser239) phosphorylation induced by exposure to exogenous NO exposure relative to their normal human fibroblasts (NHF) counterparts. Objective 2 was to understand the underlying Unfolded Protein Response (UPR)/ER stress-mediated mechanisms responsible for the induction of endothelial dysfunction. We observed that ER stress and oxidative stress collectively cause elevations in plasma membrane cholesterol in endothelial cells and aortic cross-sections of ER stressed C57BL6 mice. The rise in plasma membrane cholesterol was associated with decreased eNOS activity, eNOS phosphorylation and increased eNOS localization to the Golgi. Interestingly, we observed that neutral sphingomyelinase 2 (NSMase2) becomes dysfunctional during ER stress and by S-nitrosation of cysteine and nitration of tyrosine residues. This study is the first in its kind which links the attenuation of endothelial NO production to ER stress-mediated increases in plasma membrane cholesterol and implicates a key role for NSMase2 in this process

Selection of Appropriate Inhibitor for Ovarian Type Cytochrome P450 Aromatase Gene of Heteropneustesfossilis with the Application of Homology Modeling, Molecular Docking and ADMET Analysis

Background: Cytochrome P450 aromatase (Cyp P450 arom) is an important steroidogenic enzyme responsible for conversion of androgens to estrogens and therefore it plays a critical role in vertebrate reproduction. In contrast to vertebrates, teleost fish have two distinct forms of aromatase. One form predominates in ovaries (ovarian type;cyp19a1a), while the other form prevails in brain (brain aromatase;cyp19a1b). Aromatase is highly present during the differentiation of ovaries. It is also susceptible to environmental influences, particularly temperature and xenoestrogens, environmental natural and synthetic pollutants. Methods: In the present study, by applying bioinformatics approach we investigated relationship between catfish ovarian aromatase to its inhibitor related compounds or drugs. The three dimensional (3D) structure of cyp19a1ais not predicted experimentally, so its structure is modelled by using comparative modelling approach and further validated by various tools like RAMPAGE, ProSa, Errat. Various bioinformatics approaches such asUniprot, Homology modeling, Molecular docking, ADMET analysis were followed for the selection of appropriate aromatase inhibitor. We mainly emphasised on Docking that was carried out by Autodock 4.2. The ligand molecules docked into the structures of macromolecular targets (aromatase) and as a result of docking we came to know about different Binding Energies of different inhibitor molecules and lastly Docked structures were analysed by Protein-Ligand Interaction Profiler. Results: Predicted protein model described in this work may be further used for finding interactions with other proteins involved in different types of diseases. Among the drugs Exemestane is highly structurally similar to known active compounds. The selected compounds were further analysed and refined using drug-likeness and ADMET (Absorption, Distribution, Metabolism, Excretion and Toxicity) analysis and with the help of tools we predicted about pharmacokinetic, metabolic, toxicity endpoints. Conclusion: The study showed that how in silico approaches will further increase our ability in the discovery of appropriate drug in the form of Exemestane (which is most stable and perfect aromatase inhibitor among various selected inhibitors). Overall, findings of this study may be helpful in designing the novel therapeutic targets to cure aromatase related cancer disorders

Bioinformatic Analysis, Structure Modeling and Active Site Prediction of Aquaporin Protein from Catfish Heteropneustes fossilis

Aquaporins (AQPs) are membrane channel proteins which facilitate the rapid transport of water across cellular membrane and are of fundamental importance to the control of cell volume and transcellular water traffic. In the present study using bioinformatic tools an in silico modeling and analysis of aquaporin protein sequences of catfish Heteropneustes fossilis was conducted. Primary structure prediction and physiochemical characterization were performed by computing theoretical isoelectric point (pI), molecular weight, extinction coefficient, instability index and aliphatic index. Secondary structure assessment of aquaporin protein of Indian catfish using GOR IV reveals greater percentage of residues as alpha helix and random coils against the beta sheets. After performing homology modeling using MODELLER, a 3D structure of aquaporin of Indian catfish have been predicted from its amino acid sequence. After the prediction structure has been validated through various validation tools. This homology modeling based structure will provide an insite to its functional aspect and further studies which are based on tertiary structure of protein. Active site of aquaporin protein has been predicted using DoGSite scorer. Analysis of aquaporin active site will provide an insight to more précised functional characterization of this protein. In future, present study will allow the designing of mutant and inhibitors for the study of physiological role of aquaporin protein in Heteropneustes fossilis

Bracelet Creases among Twins

Bracelet creases among the twins were examined. A total of 42 pairs of twins (monozygotic twins-16 pairs, dizygotic like sex twins-20 pairs and dizygotic unlike sex twins-6 pairs) from the states of West Bengal and Madhya Pradesh of India were studied for this purpose. High discordance value in dizygotic twins in various types of bracelet creases is found to be sufficient to account for the high estimates of heritability. Estimated value of heritability (0.80), however, corroborates this finding. This is indicative of major role played by genetic factors in the expression of the trait as compared to environmental factors

Genetic architecture of the shell characteristics in the marine snail Littorina saxatilis

Speciation is a key process underlying biodiversity. This process is facilitated by local adaptation, when divergent selection overcomes gene flow, resulting in the accumulation of reproductive barriers. Theory suggests that this accumulation is strongly dependent on the genetic architecture of the traits underlying local adaptation. The aim of this project was to investigate the genetic architecture of locally adaptive traits in the marine snail Littorina saxatilis. This marine snail (Littorina saxatilis) is an excellent model to study speciation and local adaptation. Two diverging ecotypes live a few metres apart in distinct habitats and face divergent selection pressures dominated by crab predation and wave action. The ecotypes have evolved traits to adapt locally that make them behaviourally and structurally distinct. The most observable differences are seen in the shell size, shape, colours and patterns. Despite the differences, the two ecotypes meet in narrow contact zones and hybridize. Intermediates between the two parental ecotypes are observed in a crab-wave environmental gradient across the hybrid zones. This situation provides an excellent opportunity to exploit the power of association mapping in the hybrid zone to elucidate the genetic architectures of the locally adaptive traits. However, a prerequisite for the application of evolutionary genetic approaches is a genomic toolbox. In Chapters 2 and 3, I describe the construction of a transcriptome assembly and high-density linkage map for this species. These genetic resources were utilized in the subsequent analyses and other studies in this system. In Chapter 4, I investigate the genetic architecture of the adaptive shell traits. Theory suggests that the ground colours or banding patterns possess Mendelian inheritance and may respond directly to selection or may be linked with genes that respond to the physical environment and may thus be affected by selection. Shell morphometric characters (size and shape) may have a more complex pattern of inheritance and tend to be responsive to the environmental conditions. Thus, shell characteristics are excellent to study divergent selection pressures and local adaptation while making it imperative to understand their underlying genetic architecture. In the current study, we applied association analysis to a single hybrid zone in Sweden to elucidate the genes underlying six shell phenotypic traits (size, shape, banding pattern, ground colours – beige, black and dark beige). We sampled individuals from the hybrid zone and implemented targeted capture-sequencing to obtain genotypic data. We identified loci associated with the black and beige ground colours and banding pattern of the shell. No significant associations with the shell shape and size were found which may suggest polygenic and complex architecture, consistent with the theoretical expectation. In addition, our analysis suggests a possible role for chromosomal inversion underlying locally adaptive traits. This thesis addressed longstanding questions regarding the genetic architecture of the adaptive shell traits in this organism and provides directions for the future follow-up studies. The genetic resources described in this thesis will assist the future studies that may address a wide-range of evolutionary questions in this species

Body composition in Nepalese children using isotope dilution: the production of ethnic-specific calibration equations and an exploration of methodological issues.

Background. Body composition is important as a marker of both current and future health. Bioelectrical impedance (BIA) is a simple and accurate method for estimating body composition, but requires population-specific calibration equations. Objectives. (1) To generate population specific calibration equations to predict lean mass (LM) from BIA in Nepalese children aged 7-9 years. (2) To explore methodological changes that may extend the range and improve accuracy. Methods. BIA measurements were obtained from 102 Nepalese children (52 girls) using the Tanita BC-418. Isotope dilution with deuterium oxide was used to measure total body water and to estimate LM. Prediction equations for estimating LM from BIA data were developed using linear regression, and estimates were compared with those obtained from the Tanita system. We assessed the effects of flexing the arms of children to extend the range of coverage towards lower weights. We also estimated potential error if the number of children included in the study was reduced. Findings. Prediction equations were generated, incorporating height, impedance index, weight and sex as predictors (R (2) 93%). The Tanita system tended to under-estimate LM, with a mean error of 2.2%, but extending up to 25.8%. Flexing the arms to 90° increased the lower weight range, but produced a small error that was not significant when applied to children <16 kg (p 0.42). Reducing the number of children increased the error at the tails of the weight distribution. Conclusions. Population-specific isotope calibration of BIA for Nepalese children has high accuracy. Arm position is important and can be used to extend the range of low weight covered. Smaller samples reduce resource requirements, but leads to large errors at the tails of the weight distribution