Towards higher female work participation in India: what can be done?

A continuous and sharp decline in the already depressed female labour force participation rate in India post 2005, particularly in the face of its rapid economic growth raises questions about the inclusiveness of the growth process. The paper recommends a set of policies based on the analysis of the nature and trends of female work participation and a brief analysis of the underlying reasons behind such trends. Women are moving out of the low productivity agricultural sector, which necessitates an increase in employment opportunities in the nonagricultural sector, particularly in rural and in semi-urban locations. Improving skills for employability, especially in manufacturing clusters (which is where the jobs are) located close to young girls’ rural homes, would help the females to join the labour force if non-agricultural jobs are growing. To release women from unpaid work in the household to join the paid labour force, it is essential to improve child care facilities and other basic service facilities, which again calls for raising the share of public expenditure in some sectors and specific facilities. For instance, increasing single working women’s housing, making public transport safer, and modifying public programmes to cater to women’s needs can pave the way for more women to engage and remain in the labour force, become active participants in the growth process, and thus achieve greater economic empowerment

E-commerce website usability analysis using the association rule mining and machine learning algorithm

The overall effectiveness of a website as an e-commerce platform is influenced by how usable it is. This study aimed to find out if advanced web metrics, derived from Google Analytics software, could be used to evaluate the overall usability of e-commerce sites and identify potential usability issues. It is simple to gather web indicators, but processing and interpretation take time. This data is produced through several digital channels, including mobile. Big data has proven to be very helpful in a variety of online platforms, including social networking and e-commerce websites, etc. The sheer amount of data that needs to be processed and assessed to be useful is one of the main issues with e-commerce today as a result of the digital revolution. Additionally, on social media a crucial growth strategy for e-commerce is the usage of BDA capabilities as a guideline to boost sales and draw clients for suppliers. In this paper, we have used the KMP algorithm-based multivariate pruning method for web-based web index searching and different web analytics algorithm with machine learning classifiers to achieve patterns from transactional data gathered from e-commerce websites. Moreover, through the use of log-based transactional data, the research presented in this paper suggests a new machine learning-based evaluation method for evaluating the usability of e-commerce websites. To identify the underlying relationship between the overall usability of the eLearning system and its predictor factors, three machine learning techniques and multiple linear regressions are used to create prediction models. This strategy will lead the e-commerce industry to an economically profitable stage. This capability can assist a vendor in keeping track of customers and items they have viewed, as well as categorizing how customers use their e-commerce emporium so the vendor can cater to their specific needs. It has been proposed that machine learning models, by offering trustworthy prognoses, can aid in excellent usability. Such models might be incorporated into an online prognostic calculator or tool to help with treatment selection and possibly increase visibility. However, none of these models have been recommended for use in reusability because of concerns about the deployment of machine learning in e-commerce and technical issues. One problem with machine learning science that needs to be solved is explainability. For instance, let us say B is 10 and all the people in our population are even. The hash function’s behavior is not random since only buckets 0, 2, 4, 6, and 8 can be the value of h(x). However, if B = 11, we would find that 1/11th of the even integers is transmitted to each of the 11 buckets. The hash function would work well in this situation

Deuterium oxide stabilizes conformation of tubulin: a biophysical and biochemical study

The present study was aimed to elucidate the mechanism of stabilization of tubulin by deuterium oxide $(D_2O)$. Rate of decrease of tryptophan fluorescence during aging of tubulin at $4^oC$ and $37^oC$ was significantly lower in $D_2O$ than in $H_2O$. Circular dichroism spectra of tubulin after incubation at $4^oC$, suggested that complete stabilization of the secondary structure in $D_2O$ during the first 24 hours of incubation. The number of available cysteine measured by DTNB reaction was decreased to a lesser extent in $D_2O$ than in $H_2O$. During the increase in temperature of tubulin, the rate of decrease of fluorescence at 335 nm and change of CD value at 222 nm was lesser in $D_2O$. Differential Scanning calorimetric experiments showed that the $T_m$ values for tubulin unfolding in $D_2O$ were $58.6^oC$ and $62.17^oC$, and in $H_2O$ those values were $55.4^oC$ and $59.35^oC$

Modulation of inhibitory activity of xylanase - α-amylase inhibitor protein (XAIP): binding studies and crystal structure determination of XAIP- II from Scadoxus multiflorus at 1.2 Å resolution

Background: Plants produce a wide range of proteinaceous inhibitors to protect themselves against hydrolytic enzymes. Recently a novel protein XAIP belonging to a new sub-family (GH18C) was reported to inhibit two structurally unrelated enzymes xylanase GH11 and α -amylase GH13. It was shown to inhibit xylanase GH11 with greater potency than that of α-amylase GH13. A new form of XAIP (XAIP-II) that inhibits α-amylase GH13 with a greater potency than that of XAIP and xylanase GH11 with a lower potency than that of XAIP, has been identified in the extracts of underground bulbs of Scadoxus multiflorus. This kind of occurrence of isoforms of inhibitor proteins is a rare observation and offers new opportunities for understanding the principles of protein engineering by nature. Results: In order to determine the structural basis of the enhanced potency of XAIP-II against α-amylase GH13 and its reduced potency against xylanase GH11 as compared to that of XAIP, we have purified XAIP-II to homogeneity and obtained its complete amino acid sequence using cloning procedure. It has been crystallized with 0.1 M ammonium sulphate as the precipitating agent and the three-dimensional structure has been determined at 1.2 Å resolution. The binding studies of XAIP-II with xylanase GH11 and α-amylase GH13 have been carried out with surface plasmon resonance (SPR). Conclusion: The structure determination revealed that XAIP-II adopts the well known TIM barrel fold. The xylanase GH11 binding site in XAIP-II is formed mainly with loop α3-β3 (residues, 102 - 118) which has acquired a stereochemically less favorable conformation for binding to xylanase GH11 because of the addition of an extra residue, Ala105 and due to replacements of two important residues, His106 and Asn109 by Thr107 and Ser110. On the other hand, the α-amylase binding site, which consists of α-helices α6 (residues, 193 - 206), α7 (residues, 230 - 243) and loop β6-α6 (residues, 180 - 192) adopts a stereochemically more favorable conformation due to replacements of residues, Ser190, Gly191 and Glu194 by Ala191, Ser192 and Ser195 respectively in α-helix α6, Glu231 and His236 by Thr232 and Ser237 respectively in α-helix α7. As a result, XAIP-II binds to xylanase GH11 less favorably while it interacts more strongly with α-amylase GH13 as compared to XAIP. These observations correlate well with the values of 4.2 × 10-6 M and 3.4 × 10-8 M for the dissociation constants of XAIP-II with xylanase GH11 and α-amylase GH13 respectively and those of 4.5 × 10-7 M and 3.6 × 10-6 M of XAIP with xylanase GH11 and α-amylase GH13 respectively

Concurrence of Danish Dementia and Cataract: Insights from the Interactions of Dementia Associated Peptides with Eye Lens α-Crystallin

Familial Danish Dementia (FDD) is an autosomal disease, which is distinguished by gradual loss of vision, deafness, progressive ataxia and dementia. Cataract is the first manifestation of the disease. In this article, we demonstrate a specific correlation between the poisoning of the chaperone activity of the rat eye lens α-crystallins, loss of lens transparency in organ culture by the pathogenic form of the Danish dementia peptide, i.e. the reduced Danish dementia peptide (redADan peptide), by a combination of ex vivo, in vitro, biophysical and biochemical techniques. The interaction of redADan peptide and lens crystallins are very specific when compared with another chaperone, HSP-70, underscoring the specificity of the pathogenic form of Danish dementia peptide, redADan, for the early onset of cataract in this disease

Deep phenotyping and genomic data from a nationally representative study on dementia in India

The Harmonized Diagnostic Assessment of Dementia for the Longitudinal Aging Study in India (LASI-DAD) is a nationally representative in-depth study of cognitive aging and dementia. We present a publicly available dataset of harmonized cognitive measures of 4,096 adults 60 years of age and older in India, collected across 18 states and union territories. Blood samples were obtained to carry out whole blood and serum-based assays. Results are included in a venous blood specimen datafile that can be linked to the Harmonized LASI-DAD dataset. A global screening array of 960 LASI-DAD respondents is also publicly available for download, in addition to neuroimaging data on 137 LASI-DAD participants. Altogether, these datasets provide comprehensive information on older adults in India that allow researchers to further understand risk factors associated with cognitive impairment and dementia.Peer reviewe

Genomic And Proteomic Studies On Arsenic Toxicity

be positively correlated with their respective intracellular ROS level, which is consistent with the significant variation found in ND3 gene among the exposed individuals. In addition, the extent of potentially damaging variants in arsenic-exposed individuals had significant positive correlation to the degree of G0/G1 cell cycle arrest.In the context of understanding the underlying molecular mechanisms that render a person susceptible to arsenic toxicity it was imperative to look for the differentially expressed proteins (a) among the arsenic exposed and unexposed individuals, and (b) among the arsenic exposed individuals with and without skin lesion. To address this problem, plasma samples from 40 individuals expose to arsenic (20 symptomatic, 20 asymptomatic) and 20 unexposed individuals were taken as discovery cohort and subjected to iTRAQ followed by mass spectrometry analysis. A replicative cohort comprising of total 30 individuals (10 symptomatic, 10 asymptomatic and 10 unexposed) were also similarly subjected to iTRAQ based protein quantitation. A total of 103 proteins were identified to be differentially expressed among the three groups in both the discovery and replicative cohorts. The proteins thus identified were enriched in several biological processes like apoptosis, cellular adhesion,endothelial processes, immune responses, etc. defined by Gene Ontology terms and determined by online free software Genecodi(http://genecodis.cnb.csic.es/). Further, OMIM analysis revealed that defects in genes like APOE and DSG1 lead to skin lesion. The “skin lesion phenotype” caused due to defects in DSG1 is very similar to the type of skin lesion caused by arsenicosis. To check whether genetic defect of this gene is actually related to arsenic induced skin lesion, the entire DSG1 gene along with its regulatory regions were screened in 25 symptomatic and 25 asymptomatic individuals. In this pilot study no significant change was observed in the DSG1 gene. Interestingly, APOE isoforms have been recently reported to be associated with cardiovascular disease in the arsenic exposed individuals of Taiwan. When the APOE isoforms as well as the promoter SNPs were determined in our population of arsenic exposed individuals (100 symptomatics and 100 asymptomatics) significant association was observed. Further, DSG1, DAPK3 and APOE, found to be differentially expressed by iTRAQ, were validated by Western Blot in individual plasma samples

Role of Glycosylation and Oligomerization on the Stability of Soybean Agglutinin

Carbohydrates are vital to life. In their naive form, they serve as a primary energy source for supporting life. However, in most cases carbohydrates do not exist as simple sugars in nature. Instead they occur as more complex molecular conjugates known as the glycans and Glycobiology is the study of the roles of these glycans in various biological events. The study of sugars is gaining importance in all strata of today’s scientific world, be it cell biology, immunology or even neurobiology. These glycans do not exist at the cell surface or in the extracellular matrix as free-standing polymers. Rather, they are organized onto specific proteins to form protein-glycan conjugates. One such specific class of proteins is the lectins. Lectins are ubiquitously distributed in nature and are recognized universally by their property of carbohydrate recognition. Much work has been done in the field of lectins to delineate the roles of different lectins in their recognition events and proper propagation of the protein folding machinery. However, these studies mainly concentrate on the animal lectins. Nonetheless, a good deal of structural work has been done on plant lectins and these plant lectins serve as excellent paradigms to work on the ever-exciting problem of protein folding. This thesis primarily concentrates on a glycoprotein plant lectin, Soybean agglutinin. I have mainly addressed the issues of glycosylation and oligomerization on the stability of the protein. Chapter 1 is a prelude to glycosylation in proteins and their functions in vivo. Glycosylation, particularly the N-linked kind, profoundly affects protein folding, oligomerization, and stability. The increased efficiency of folding of glycosylated proteins could be due to the chaperone like activity of glycans, which is observed even when the glycan is not attached to the protein. Covalently linked glycans could also facilitate oligomerization by mediating inter-subunit interactions in the protein or stabilizing the oligomer in other ways. Glycosylation is also seen to affect the rate of fibril formation in prion proteins, with N-glycans reducing the rate of fibril formation, and O-glycans affecting the rate either way based on factors such as position and orientation. While it is still not apparent if there is a common theme in the significance of glycosylation sites in multiply glycosylated proteins or in the conservation of glycans in a related family of glycoproteins, it is evident that glycosylation is a multifaceted post translational modification that incredibly affects proteins. This is followed by a brief description on lectins, their structure, and functions with the emphasis on the various kinds of quaternary associations that they are involved in. Further I have also included a very concise discussion on the major forces involved in protein folding and stability. Chapter 2 deals with the stability studies of two structurally similar legume lectins, Soybean agglutinin and Concanavalin A. The unfolding pathway of these two legume lectins are determined using GdnCl induced denaturation. Both displayed a reversible two-state unfolding mechanism. The analysis of isothermal denaturation data provided values for conformational stability of the two proteins. It was found that the DG of unfolding of SBA was much higher than Con A at all the temperatures at which the experiments were done. Con A had a Tg 18°C lower than SBA. The higher conformational stability of SBA in comparison to Con A is largely due to substantial differences in their degrees of subunit interactions. Ionic interactions at the interface of the two proteins especially at the non-canonical interface seem to play a significant role in the observed stability differences between these two proteins. Further, SBA is a glycoprotein with a GlcNac2Man9 chain attached to Asn-75 of each subunit. The sugar chain in SBA spans the entire non-canonical interface of the protein. However, the entire glycan chain in SBA is not seen in its crystal structure. Only the two proximal GlcNac residues are visible in the crystal structure of the protein. I probed the interactions of these two sugar residues with the amino acid residues of the protein and determined that there were a number of inter-subunit interactions. These interactions further stabilize SBA with respect to Con A, which is not glycosylated. In Chapter 3 I have presented my investigations on the role of glycosylation in the stability of the glycoprotein SBA. I have used the non-glycosylated recombinant form of the protein rSBA expressed in E. coli cells for the stability studies and compared it with the native glycosylated form. The non-glycosylated form features a lower stability when compared to the glycosylated form. Further the unfolding pathways in the two are widely different. While the glycosylated form undergoes a simple two state unfolding, the non-glycosylated species unfolds via a compact monomeric intermediate which is not a molten globule. Representative isothermal and thermal denaturation profiles show that glycosylation accounts for a stabilization of nearly 9 kcal/mol of the tetramer, while the difference in Tm in the two forms is 26oC. To my knowledge this is the first report which shows that glycosylation imparts huge conformational stability to the macromolecule to which it is attached. As already mentioned, the density for the entire oligomannosidic chain is not observed in the crystal structure of the protein. Hence, I attempted to obtain a three-dimensional structure of the glycoprotein by combining the structure of the protein (from the protein data bank) and the glycan (from the www.glycosciences.de database). The glycoprotein thus obtained portrayed substantial inter-subunit glycan protein interactions (hydrogen bonding and hydrophobic) which is perhaps the major cause for the stability of the glycoprotein tetramer. In Chapter 4 I present the thermodynamic analysis on the monomer of SBA and estimate the stability of SBA monomer. Almost all legume lectins show oligomerization-deoligomerization with change in pH. However, pH dependent association/dissociation was not reported for SBA. As evident from size exclusion chromatographic and dynamic light scattering studies, I show that the monomeric form of the protein is existent at pH 1.9. The analyses of CD and fluorescence spectroscopy suggest that the monomer is well folded, and it has a very different characteristic feature when compared to the tetramer. The conformational stabilities of the tetramer and the monomer at the temperature of their maximum stabilities were widely different indicating that oligomerization contributes huge stability to the native molecule. Also, the Tg difference in the two forms of the protein is~40K, while the difference in DCp is only 1.6kcal/mol/K. This suggests that the major hydrophobic core is present in the monomer and oligomerization involves mainly ionic interactions. The thesis ends with a summary of all the findings in Chapter 5. I have tried to review the vital factors that contribute to the stability and quaternary integrity of the protein. Brief discussions involving the roles of oligomerization and glycosylation have been discussed. Further I have also tried to focus on the various unfolding thermodynamic parameters obtained by solution denaturation studies of glycosylated SBA, non-glycosylated SBA and the monomer of SBA and give a comparative account of all with the possible rationale for the variations. Appendix A deals with one of the much-discussed issues of the recent times: the use of quantum dots in biology as imaging and targeting agents. The quantum dots surpass the already accessible existing organic fluorophores by virtue of fluorescence, resistance to photo bleaching and optical properties that facilitate the simultaneous imaging of multiple fluorophores. One-pot synthesized neoglycoconjugates with reactive thiol group are introduced here for functionalization with carbohydrates for solubilization and stabilization of CdSe-ZnS quantum dots (QDs) in aqueous solution. Three different sizes of QDs with lactose, melibiose and maltotriose on them surface have been utilized, for the first time, for lectin detection through agglutination assay. Agglutination of Sugar-QDs (S-QDs) by three different lectins occurred through specific carbohydrate-lectin interactions and was studied extensively by monitoring the scattered light at 600 nm. This assay is very selective, which has been demonstrated by a more selective binding of Soybean agglutinin (SBA) with melibiose-QD as compared to lactose- QD, and specific de-agglutination caused by a-D-galactose while a-Dmannose did not show any effect. The detection sensitivity of the maltotriose-QD was tested with Concanavalin A (ConA), and as low as 100 nM of the lectin was detected using light scattering. Furthermore, the visual detection sensitivity of S-QDs has been enhanced by the emission properties of semiconductor QDs

Attributes of Glycosylation in the Establishment of the Unfolding Pathway of Soybean Agglutinin

Soybean agglutinin (gSBA) is a tetrameric legume lectin, each of whose subunits are glycosylated. Earlier studies have shown that this protein shows exceptionally high stability in terms of free energy of unfolding when compared to other proteins from the same family. This article deals with the unfolding reactions of the nonglycosylated recombinant form of the protein rSBA and its comparison with the glycosylated counterpart gSBA. The nonglycosylated form features a lower stability when compared to the glycosylated form. Further, the unfolding pathways in the two are widely different. Although the glycosylated form undergoes a simple two-state unfolding, the nonglycosylated species unfolds via a compact monomeric intermediate that is not a molten globule. Representative isothermal and thermal denaturation profiles show that glycosylation accounts for a stabilization of ∼9 kcal/mol of the tetramer, whereas the difference in T(m) between the two forms is 26°C. Computational studies on the glycan-protein interactions at the noncanonical interface of the protein show that quite a number of hydrogen bond and hydrophobic interactions stabilize the glycoprotein tetramer