Biological characterization of hYVH1

Human YVH1 is an atypical dual specificity phosphatase (DSP) that is widely conserved throughout evolution. Deletion studies in yeast have suggested a role for this phosphatase in regulating cell growth, sporulation, and glycogen accumulation. However, the functional role of the human orthologue is unknown. This study examines the interaction between hYVH1 and a recently identified binding partner Hsp70, in addition to deciphering domains and motifs important in hYVH1 localization. The results established that the zinc binding domain mediates the subcellular targeting of hYVH1. Moreover, a putative nuclear export sequence was identified to have some effect on the shuttling of hYVH1 between the nucleus and cytoplasm. Hsp70 and hYVH1 were found to be colocalized to the perinuclear region following heat stress. Furthermore, hYVH1 expression repressed heat shock induced cell death. The results suggest that hYVH1 cooperates with Hsp70 to positively affect cell viability by targeting the MAPK signaling pathway

Application of Cone Beam Computerized Tomography in Implantology

Dental implants have gained immense popularity and wide acceptance because of its appearance and function simulating a natural tooth and its ability to replace the crown as well as the root of the missing tooth. It is important for dentists to be able to place the implants in the mandible and maxilla with a high degree of precision. The greater accuracy of Cone Beam Computed Tomography (CBCT) in measurements at lower radiation doses has made it a preferred option in implant dentistry. It has led to improvements in case selection and aids in both qualitative and quantitative measurement of bone, leading to a reduction in implant failure. This article provides an overview of the potential use of CBCT in implantology

Exploring the Relationship between Skin Tone and Self-esteem Among Females in South Asian Families in India: A Multigenerational Comparison

Colourism or skin colour stratification is a persistent dilemma for people in India. Socially and culturally constructed definitions of beauty based on skin tone, represent Western realities and continue to sustain beauty ideals that shape the beliefs and practices around fair skin for women. The study of skin tone and its relationship to self-esteem is essential in expanding upon the limited research examining the intersections between body image and the sociocultural experiences of South Asian Indian women. Against the backdrop of Western hegemony, the research discusses how a fair skin beauty ideal impacts different generations of women in New Delhi. More specifically, investigating the relationship between skin tone and self-esteem among women in South Asian families through a multigenerational comparison, provides a deeper understanding of how skin tone bias is perpetuated, while reinforcing and normalizing white heteropatriarchy. Skin tone bias is disseminated through the family, culture and media. The narratives highlight how skin tone bias manifests itself among adult women in different South Asian family units according to their life stage and membership in the family. Women from the young age group (generation) had the lowest self-esteem and faced the most pressure to conform to white skin beauty ideals when compared to older generations in their families. Skin tone appeared to be heavily emphasized for these young women, namely in the context of marriage.Ph.D

Inhibition of Oxidation-Induced Misfolding of Mutant SOD1 in ALS using Small Molecules

Abstract Amyotrophic lateral sclerosis (ALS) is a neurodegenerative disease characterized by the loss of motor neurons resulting in progressive paralysis that eventually leads to the death of an afflicted individual. In a majority of ALS cases, the cause of onset is unknown, but a small subset of ALS cases are linked to mutations in the protein Cu, Zn superoxide dismutase (SOD1). Despite extensive research in this area, few treatments for ALS have been developed. Since the description of the disease by Jean-Martin Charcot in the mid-nineteenth century, only one drug, Riluzole has been approved in the management of this disease. We propose investigating therapeutic treatments of ALS by looking for small molecules that have the potential to stabilize the native structure of mutant SOD1 and prevent its misfolding and aggregation. We started our investigation by first devising a method to optimize the purification of wildtype and mutant SOD1 in our lab. We constructed a fusion protein of SOD1 linked to a yellow fluorescent protein, a hexahistidine tag, and a tobacco etch virus (TEV) cleavage site and showed that both wildtype and mutant SOD1 purified from this construct was active and metallated. We used our purified protein to explore the results of an in silico binding screen searching for SOD1 native-state binders. We discovered the flavonoid, epigallocatecin-3-gallate (EGCG) was able to inhibit the misfolding and aggregation of the ALS-causing mutation A4V-SOD1 exposed to oxidative stress. Additionally, we have evidence that the inhibitory effect of EGCG occurs through the stabilization of the dimer interface of mutant SOD1, rather than the anti-oxidant properties of this molecule. This is the first report of EGCG having anti-aggregation properties in an ALS model and these results implicate the potential therapeutic value of EGCG within the field of SOD1-ALS.Ph.D

Cloning and comparative modeling identifies a highly stress tolerant Cu/Zn cytosolic super oxide dismutase 2 from a drought tolerant maize inbred line

Plants have a complex system of stress response that deals with different types of stresses. Maize (Zea mays L.), one of the most important crops grown throughout the world, across a range of agro-ecological environments, employs complex mechanisms of gene regulation in response to drought stress. HKI 335 is a tropical maize inbred line showing remarkable adaptation to drought stress. Abiotic stresses, like drought, trigger the production of reactive oxygen species (ROS) due to the incomplete reduction or excitation of molecular oxygen, eventually leading to cell damage. Superoxide dismutase (SOD, EC 1.15.1.1) is a metalloenzyme that acts as the first line of defense against ROS. We cloned the Sod2 gene from HKI 335 inbred line and analyzed its protein through detailed in silico characterization. Our comparative modeling revealed that at the level of tertiary structure, the HKI 335 SOD2 protein is highly similar to Potentilla atrosanguinea SOD2, which had been previously identified as highly thermostable SOD that can tolerate autoclaving as well as sub-zero temperatures. We performed phylogenetic analysis, estimated physicochemical properties, post-translational modifications, protein-protein interactions, and domain composition of this SOD2. The phylogenetic analysis showed that orthologous sequences of SOD from different species were clustered into two clusters. Secondary structure prediction indicates that SOD2 is a soluble protein and no transmembrane domains have been found. Most of the beta sheets have RSA value greater than 2. The Ramachandran plot from PDBsum revealed that most of the residues fall in the highly favored region. It was estimated that the value of the instability index was less than 40, the value of the aliphatic index was extremely high and the GRAVY value lies between −2 and +2. We could identify only one phosphorylation site, located at position 20 with a score of 0.692. Overall, the unique stress-tolerant properties of the HKI 335 SOD2, may be one of the reasons contributing to the high drought tolerance trait exhibited by HKI 335 maize inbred line. Further research may reveal more insights into the drought adaptation mechanism in maize and the eventual deployment of the trait in maize hybrids

Managing groundwater for building resilience for sustainable agriculture in South Asia

South Asia's heavy reliance on groundwater for irrigated agricultural production supports the livelihoods of tens of millions of smallholder farmers but is being undermined by rampant overexploitation of groundwater. Without major intervention, this is expected to be further exacerbated by growing demand and climate change. Groundwater management, scientific and evidence-based, can make an important contribution to managing unsustainable groundwater use and strengthening the climate resilience of farmers due to groundwater's unique storage characteristics. This study brings together a set of strategies and solutions to better manage groundwater that cover the augmentation of groundwater recharge through managed aquifer recharge, management of groundwater demand through participatory groundwater management and other methods, and the harnessing synergies of co-dependent sectors. The opportunities, constraints and available evidence for each are analysed and the boundaries, barriers and specificities identified to establish entry points for positive change through policies and implementation programmes