Dr Neena Singh | Govind Ballab pant university of Agriculture and Technology (original) (raw)
Papers by Dr Neena Singh
Discuses situation of Library Legislation and Development of Library and Information Centers in I... more Discuses situation of Library Legislation and Development of Library and Information Centers in India, challenges and opportunities , role of national knowledge commission etc.
Free radical biology & medicine, Jan 7, 2015
Excess circulating iron is stored in the liver, and requires reduction of non-Tf-bound-iron (NTBI... more Excess circulating iron is stored in the liver, and requires reduction of non-Tf-bound-iron (NTBI) and transferrin (Tf)-iron at the plasma membrane and endosomes respectively by ferrireductase (FR) proteins for transport across biological membranes through divalent metal transporters. Here, we report that prion-protein (PrP(C)), a ubiquitously expressed glycoprotein most abundant on neuronal cells, functions as a FR partner for divalent-metal transporter-1 (DMT1) and ZIP14. Thus, absence of PrP(C) in PrP-knock-out (PrP(-/-)) mice resulted in markedly reduced liver iron stores, a deficiency that was not corrected by chronic or acute administration of iron by the oral or intra-peritoneal routes. Likewise, preferential radiolabeling of circulating NTBI with (59)Fe revealed significantly reduced uptake and storage of NTBI by the liver of PrP(-/-) mice relative to matched PrP(+/+) controls. However, uptake, storage, and utilization of ferritin-bound iron that does not require reduction f...
Journal of Alzheimer's disease : JAD, 2003
Although familial prion disorders are a direct consequence of mutations in the prion protein gene... more Although familial prion disorders are a direct consequence of mutations in the prion protein gene, the underlying mechanisms leading to neurodegeneration remain unclear. Potential pathogenic mechanisms include abnormal cellular metabolism of the mutant prion protein (PrP(M)), or destabilization of PrP(M) structure inducing a change in its conformation to the pathogenic PrP-scrapie (PrP(Sc)) form. To further clarify these mechanisms, we investigated the biogenesis of mutant PrP V203I and E211Q associated with Creutzfeldt-Jakob disease, and PrP Q212P associated with Gerstmann-Straussler-Scheinker syndrome in neuroblastoma cells. We report that all three PrP(M) forms accumulate similarly in the cytosol in response to proteasomal inhibition, and finally assemble as classical aggresomes. Since the three PrP(M) forms tested in this report are distinct, we propose that sequestration of misfolded PrP(M) into aggresomes is likely a general response of the cellular quality control that is not...
Discusses LIS course content followed by 17 universities of agricultural sciences in the country.... more Discusses LIS course content followed by 17 universities of agricultural sciences in the country. Analyses the suitability of these courses in achieving the objectives laid down and evaluates the course content in changing context and the need for restructuring the course curricula in present context. Suggests a separate one credit course on LIS user education and a separate course on technical writing.
Journal of Alzheimer's disease : JAD, 2013
Prion protein (PrPC) is implicated in the pathogenesis of prion disorders, but its normal functio... more Prion protein (PrPC) is implicated in the pathogenesis of prion disorders, but its normal function is unclear. We demonstrate that PrPC is a ferrireductase (FR), and its absence causes systemic iron deficiency in PrP knock-out mice (PrP-/-). When exposed to non-transferrin-bound (NTB) radioactive-iron (59FeCl3) by gastric-gavage, PrP-/- mice absorb significantly more 59Fe from the intestinal lumen relative to controls, indicating appropriate systemic response to the iron deficiency. Chronic exposure to excess dietary iron corrects this deficiency, but unlike wild-type (PrP+/+) controls that remain iron over-loaded, PrP-/- mice revert back to the iron deficient phenotype after 5 months of chase on normal diet. Bone marrow (BM) preparations of PrP-/- mice on normal diet show relatively less stainable iron, and this phenotype is only partially corrected by intraperitoneal administration of excess iron-dextran. Cultured PrP-/- BM-macrophages incorporate significantly less NTB-59Fe in th...
Journal of Neuroscience, 2004
Foodborne transmission of bovine spongiform encephalopathy (BSE) to humans as variant Creutzfeldt... more Foodborne transmission of bovine spongiform encephalopathy (BSE) to humans as variant Creutzfeldt-Jakob disease (CJD) has affected over 100 individuals, and probably millions of others have been exposed to BSE-contaminated food substances. Despite these obvious public health concerns, surprisingly little is known about the mechanism by which PrP-scrapie (PrP(Sc)), the most reliable surrogate marker of infection in BSE-contaminated food, crosses the human intestinal epithelial cell barrier. Here we show that digestive enzyme (DE) treatment of sporadic CJD brain homogenate generates a C-terminal fragment similar to the proteinase K-resistant PrP(Sc) core of 27-30 kDa implicated in prion disease transmission and pathogenesis. Notably, DE treatment results in a PrP(Sc)-protein complex that is avidly transcytosed in vesicular structures across an in vitro model of the human intestinal epithelial cell barrier, regardless of the amount of endogenous PrP(C) expression. Unexpectedly, PrP(Sc) is cotransported with ferritin, a prominent component of the DE-treated PrP(Sc)-protein complex. The transport of PrP(Sc)-ferritin is sensitive to low temperature, brefeldin-A, and nocodazole treatment and is inhibited by excess free ferritin, implicating a receptor- or transporter-mediated pathway. Because ferritin shares considerable homology across species, these data suggest that PrP(Sc)-associated proteins, in particular ferritin, may facilitate PrP(Sc) uptake in the intestine from distant species, leading to a carrier state in humans.
Libri, 2000
Information technology has brought a tremendous change in the nature, boundaries and structure of... more Information technology has brought a tremendous change in the nature, boundaries and structure of information. The ongoing movement towards an electronic information society is pushing libraries towards automation and digitization. The revolution has brought impressive changes in the role of LIS professionals who are now being viewed as information managers/facilitators. These developments have also influenced LIS writings and publishing. This study shows that while the application of IT has gained considerable importance in Indian libraries, IT-based papers have surprisingly found less space in Indian LIS periodicals as compared to the LIS literature in general. The findings of this study also indicate that there is an uneven distribution of various topics within the Indian LIS ITpublished literature; while some topics/areas of IT have received considerable attention others have been barely touched. Topics like IT in general, bibliographic databases, library networking, library automation and electronic resources have been found to predominate in the growth of Indian LIS literature as compared to the coverage of other areas of IT. Most papers (60 %) have single authors, indicating a low amount of teamwork/collaborative writing. The paper's analysis also reveals that working professionals/librarians have made more contributions (48%) in comparison to teaching professionals (22%).
Journal of Biological Chemistry, 2002
A familial prion disorder with a proline to leucine substitution at residue 102 of the prion prot... more A familial prion disorder with a proline to leucine substitution at residue 102 of the prion protein (PrP 102L ) is typically associated with protease-resistant PrP fragments (PrP Sc ) in the brain parenchyma that are infectious to recipient animals. When modeled in transgenic mice, a fatal neurodegenerative disease develops, but, unlike the human counterpart, PrP Sc is lacking and transmission to recipient animals is questionable. Alternate mice expressing a single copy of PrP 102L (mouse PrP 101L ) do not develop spontaneous disease, but show dramatic susceptibility to PrP Sc isolates from different species. To understand these discrepant results, we studied the biogenesis of human PrP 102L in a cell model. Here, we report that cells expressing PrP 102L show decreased expression of the normal 18-kDa fragment on the plasma membrane. Instead, a 20-kDa fragment, probably derived from transmembrane PrP ( Ctm PrP), accumulates on the cell surface. Because the 20-kDa fragment includes an amyloidogenic region of PrP that is disrupted in the 18-kDa form, increased surface expression of 20-kDa fragment may enhance the susceptibility of these cells to PrP Sc infection by providing an optimal substrate, or by amplifying the neurotoxic signal of PrP Sc . Thus, altered susceptibility of PrP 101L mice to exogenous PrP Sc may be mediated by the 20-kDa Ctm PrP fragment, rather than PrP 102L per se.
Journal of Biological Chemistry, 2010
Filamin A (FLNA) is an integrator of cell mechanics and signaling. The spreading and migration ob... more Filamin A (FLNA) is an integrator of cell mechanics and signaling. The spreading and migration observed in FLNA sufficient A7 melanoma cells but not in the parental FLNA deficient M2 cells have been attributed to FLNA. In A7 and M2 cells, the normal prion (PrP) exists as pro-PrP, retaining its glycosylphosphatidyl-inositol (GPI) anchor peptide signal sequence (GPI-PSS). The GPI-PSS of PrP has a FLNA binding motif and binds FLNA. Reducing PrP expression in A7 cells alters the spatial distribution of FLNA and organization of actin and diminishes cell spreading and migration. Integrin β1 also binds FLNA. In A7 cells, FLNA, PrP, and integrin β1 exist as two independent, yet functionally linked, complexes; they are FLNA with PrP or FLNA with integrin β1. Reducing PrP expression in A7 cells decreases the amount of integrin β1 bound to FLNA. A PrP GPI-PSS synthetic peptide that crosses the cell membrane inhibits A7 cell spreading and migration. Thus, in A7 cells FLNA does not act alone; the binding of pro-PrP enhances association between FLNA and integrin β1, which then promotes cell spreading and migration. Pro-PrP is detected in melanoma in situ but not in melanocyte. Invasive melanoma has more pro-PrP. The binding of pro-PrP to FLNA, therefore, contributes to melanomagenesis.
Frontiers in Bioscience, 2002
Prion diseases or transmissible spongiform encephalopathies are neurodegenerative disorders that ... more Prion diseases or transmissible spongiform encephalopathies are neurodegenerative disorders that are genetic, sporadic, or infectious. The pathogenetic event common to all prion disorders is a change in conformation of the cellular prion protein (PrPC) to the scrapie isoform (PrPSc), which, unlike PrPC, aggregates easily and is partially resistant to protease digestion. Although PrPSc is believed to be essential for the pathogenesis and transmission of prion disorders, the mechanism by which PrPSc deposits cause neurodegeneration is unclear. It has been proposed that in some cases of prion disorders, a transmembrane form of PrP, termed CtmPrP may be the mediator of neurodegenerative changes rather than PrPSc per se. In order to understand the underlying cellular processes by which PrPSc mediates neurodegeneration, we have investigated the mechanism of neurotoxicity by a beta-sheet rich peptide of PrP in a cell model. We show that exposure of human neuronal cell lines NT-2 and M17 to the prion peptide 106-126 (PrP106-126) catalyzes the aggregation of endogenous cellular prion protein (PrPC) to an amyloidogenic form that shares several characteristics with PrPSc. Intracellular accumulation of these PrPSc-like forms upregulates the synthesis of CtmPrP, which is proteolytically cleaved in the endoplasmic reticulum and the truncated C-terminal fragment is transported to the cell surface. In addition, we have isolated mutant NT-2 and neuroblastoma cells that are resistant to toxicity by PrP106-126 to facilitate further characterization of the biochemical pathways of PrP106-126 neurotoxicity. The PrP106-126-resistant phenotype of these cells could result from aberrant binding or internalization of the peptide, or due to an abnormality in the downstream pathway(s) of neuronal toxicity. Thus, our data suggest that PrPSc aggregation occurs by a process of 'nucleation' on a pre-existing 'seed' of PrP. Furthermore, the PrP106-126-resistant cells reported here will provide a unique opportunity for identifying the cellular and biochemical pathways that mediate neurotoxicity by PrPSc.
Molecular Brain Research, 2004
Familial Creutzfeldt -Jakob disease (CJD) comprises a group of neurodegenerative disorders for wh... more Familial Creutzfeldt -Jakob disease (CJD) comprises a group of neurodegenerative disorders for which currently there is no treatment. In this study, we evaluated the efficacy of drugs approved for human use, and protein folding agents in reversing the mutant phenotype of familial CJD H187R in a cell model. For an efficient experimental readout, green fluorescent protein (GFP)-tagged mutant prion protein (PrP 187R-GFP ) and wild-type PrP (PrP C-GFP ) were expressed in human neuroblastoma cells. We report that unlike PrP C-GFP that is expressed on the cell surface, PrP 187R-GFP accumulates in the lysosomes of transfected cells. Treatment of PrP 187R-GFP cells with quinacrine or doxycycline, agents known to inhibit the replication of PrP-scrapie (PrP Sc ) in experimental models, gave conflicting results; doxycycline reverted the mutant phenotype of PrP 187R-GFP cells, whereas quinacrine had no effect. The concentration of doxycycline used in these studies is well within the plasma concentration of patients receiving a 250 -600 mg dose two to three times daily. Interestingly, exposure of PrP 187R-GFP cells to low temperature (28jC) or to the chemical chaperones dimethyl sulphoxide (DMSO) and glycerol also reversed the mutant phenotype. These data suggest that doxycycline and protein folding agents may hold promise as therapeutic agents for familial CJD H187R and other familial disorders that share similar pathogenic mechanisms. D
Antioxidants & Redox Signaling, 2013
Aims: Most biomarkers used for the premortem diagnosis of sporadic Creutzfeldt-Jakob disease (CJD... more Aims: Most biomarkers used for the premortem diagnosis of sporadic Creutzfeldt-Jakob disease (CJD) are surrogate in nature, and provide suboptimal sensitivity and specificity. Results: We report that CJD-associated brain iron dyshomeostasis is reflected in the cerebrospinal fluid (CSF), providing disease-specific diagnostic biomarkers. Analysis of 290 premortem CSF samples from confirmed cases of CJD, Alzheimer's disease, and other dementias (DMs), and 52 non-DM (ND) controls revealed a significant difference in ferroxidase (Frx) activity and transferrin (Tf) levels in sporadic Creutzfeldt-Jakob disease (sCJD) relative to other DM and ND controls. A combination of CSF Frx and Tf discriminated sCJD from other DMs with a sensitivity of 86.8%, specificity of 92.5%, accuracy of 88.9%, and area-under-the receiver-operating-characteristic (ROC) curve of 0.94. This combination provided a similar diagnostic accuracy in discriminating CJD from rapidly progressing cases who died within 6 months of sample collection. Surprisingly, ceruloplasmin and amyloid precursor protein, the major brain Frxs, displayed minimal activity in the CSF. Most of the Frx activity was concentrated in the < 3-kDa fraction in normal and diseased CSF, and resisted heat and proteinase-K treatment. Innovation: (i) A combination of CSF Frx and Tf provides disease-specific premortem diagnostic biomarkers for sCJD. (ii) A novel, nonenzymatic, nonprotein Frx predominates in human CSF that is distinct from the currently known CSF Frxs. Conclusion: The underlying cause of iron imbalance is distinct in sCJD relative to other DMs associated with the brain iron imbalance. Thus, change in the CSF levels of iron-management proteins can provide disease-specific biomarkers and insight into the cause of iron imbalance in neurodegenerative conditions.
Prion disease associated neurotoxicity is mainly attributed to PrP-scrapie (PrP Sc ), the disease... more Prion disease associated neurotoxicity is mainly attributed to PrP-scrapie (PrP Sc ), the disease associated isoform of a normal protein, the prion protein (PrP C ). Participation of other proteins and processes is suspected, but their identity and contribution to the pathogenic process is unclear. Emerging evidence implicates imbalance of brain iron homeostasis as a significant cause of prion disease-associated neurotoxicity. The underlying cause of this change, however, remains unclear. We demonstrate that iron is sequestered in heat and SDS-stable protein complexes in sporadic-Creutzfeldt-Jakob-disease (sCJD) brains, creating a phenotype of iron deficiency. The underlying cause is change in the characteristics of ferritin, an iron storage protein that becomes aggregated, detergent-insoluble, and partitions with denatured ferritin using conventional methods of ferritin purification. A similar phenotype of iron deficiency is noted in the lumbar spinal cord (SC) tissue of scrapie infected hamsters, a site unlikely to be affected by massive neuronal death and nonspecific iron deposition. As a result, the iron uptake protein transferrin (Tf) is upregulated in scrapie infected SC tissue, and increases with disease progression. A direct correlation between Tf and PrP Sc suggests sequestration of iron in dysfunctional ferritin that either co-aggregates with PrP Sc or is rendered dysfunctional by PrP Sc through an indirect process. Surprisingly, amplification of PrP Sc in vitro by the protein-misfolding-cyclic-amplification (PMCA) reaction using normal brain homogenate as substrate does not increase the heat and SDS-stable pool of iron even though both PrP Sc and ferritin aggregate by this procedure. These observations highlight important differences between PrP Sc -protein complexes generated in vivo during disease progression and in vitro by the PMCA reaction, and the significance of these complexes in PrP Scassociated neurotoxicity.
The Electronic Library, 2014
e article explores how Indian Agricultural libraries have evolved and transformed in the digital... more e article explores how Indian Agricultural libraries have evolved and transformed in the digital era and how technological advances and increased sophistication of web based tools have enabled libraries to collaborate and share resources. e authors identify various innovative practices adopted by fiy six Indian agricultural libraries and detail the collaborative county-wide programs and digitization projects in progress such as eGranth's AgriCat, a union catalog of books and articles in agriculture and allied sciences. Also described are activities involving digital institutional repositories like KrishiKosh and KrishiPrabha and the establishment of a national level consortium for e-journals and digital content accessible to the Indian academic community. Grants from World Bank-ICAR funded projects like the National Agricultural Innovative Project (NAIP) have boosted digitization in India and have brought libraries and the user community into closer proximity virtually by removing physical boundaries. Resumé: L'article explore comment les bibliothèques agricoles indiennes ont évolué et se sont transformées sous l'ère nu mérique, et comment les progrès technologiques et la sophistication croissante des instruments du web ont permis aux bibliothèques de collaborer et de partager les ressources. Les auteurs identifient diverses pratiques novatrices adoptées par cin quantesix bibliothèques agricoles indiennes, et détaillent les programmes de collaboration et projets de numérisation en cours au niveau des comtés comme la eGranth AgriCat, un catalogue de livres et d'articles dans les domaines de l'agriculture et des sciences alliées. D'autres activités numériques sont aussi dé crites tels les dépôts institutionnels comme KrishiKosh et KrishiPrabha, et l'établissement d'un consortium au niveau national pour l'accès aux e-revues et au contenu numérique, par la communauté universitaire indienne. Des subventions venant de projets financés par la Banque mondiale-ICAR comme le Projet national d'agriculture novatrice (NAIP) ont stimulé la numérisation en Inde, et rapproché étroitement les bibliothèques et la communauté des utilisateurs pratiquement en supprimant les frontières physiques.
Information Literacy is receiving increasing attention among Indian professional practice with em... more Information Literacy is receiving increasing attention among Indian professional practice with emergence of electronic resources and digitization activities in libraries. As early as 1970's User instruction existed in Indian agricultural universities and were adapted from US land Grant pattern universities. Formally popularly known as User education, most universities had an embedded curriculum approach to enhance students information and research skills . This study investigates and analyses what agricultural universities are offering to enhance their students library or information skills. In addition, identifies basic contents in terms of latest developments, library skills and research skills, approach to uniformity, concept like subject librarian.Findings reveal that out of 34 universities surveyed , significantly high more than 90.0 % offer credit bearing information literacy through curriculum approach by different names, to mention a few like Research Methodology and Library Use, Technical writing and User Education, Storage and Retrieval of Scientific Information, Agricultural Information system etc. Most state universities provide such course to Graduate students and are yet to introduce structured courses for under graduates. In the year 2010 the Indian Council of Agricultural Research formulated Common Academic Regulations (CAR) and introduced a mandatory IL course entitled Library and Information Services coded PGS-501 for Post Graduate Studies. Some 20% state universities have now introduced IL as essential part of curricula after CAR. The study also points out the need for innovative perspective in mode of delivering educational content engaging greater online or e-learning experiences.
The study describes information seeking of farmers’ communities in the Himalayan state of Uttrakh... more The study describes information seeking of farmers’ communities in the Himalayan state of Uttrakhand in
India. The work reveals that there is a growing awareness among the farmers of this state and adjoining
states. 4266 queries were received by G B Pant University of Agriculture and Technology’s telecenter and
farmers helpline in the period of 2006 -2008. Farmers sought most information from the toll free telecenter
popularly known as Kissan (farmers) reference to the Information Center and use of the telecenter helpline
was found to be substantially less.The telecenters function on 3 levels. Findings reveal that most
information sought by farmers was provided in the local language by level I experts, who are Agricultural
Science Graduates. Level II involves specific queries answered by subject specialists. The Helpline of
universities functions at level II, where farmers can directly seek information from subject experts.
Maximum information was sought in the month of September followed by October and November. These
months are crucial for Rainy and Winter season crops, therefore requiring maximum attention of farmers in
protecting their standing rainfed crops and planning winter crops. 1252 queries were received during 2006
on various subjects, which gradually increased to 1315 in 2007 and 1721 queries in 2008. Most information
was sought on subjects like Agronomy and farmers’ fairs. Substantial information was also sought on plant
diseases,cultivation of vegetables, and seeds availability. Subject like solar energy, crop insurance, and silk
production have been found to be the least popular among the farming community. The study further
indicates that most information was sought on crops that provided quick cash rather than complicated
subject like use of solar energy or silk production. Most farmers in India are involved in small or marginal
farming, therefore prefer growing cash-crops as a source of income for their livelihood.
Information Literacy is receiving increasing attention among Indian professional practice with e... more Information Literacy is receiving increasing attention among Indian professional practice with emergence of electronic resources and digitization activities in libraries. As early as 1970’s User instruction existed in Indian agricultural universities and were adapted from US land Grant pattern universities. Formally popularly known as User education, most universities had an embedded curriculum approach to enhance students information and research skills . This study investigates and analyses what agricultural universities are offering to enhance their students library or information skills. In addition, identifies basic contents in terms of latest developments, library skills and research skills, approach to uniformity, concept like subject librarian.
Findings reveals that out of 34 universities surveyed , significantly high more than 90.0 % offer credit bearing information literacy through curriculum approach by different names, to mention a few like Research Methodology and Library Use, Technical writing and User Education, Storage and Retrieval of Scientific Information, Agricultural Information system etc. Most state universities provide such course to Graduate students and are yet to introduce structured courses for under graduates. In the year 2010 the Indian Council of Agricultural Research formulated Common Academic Regulations (CAR) and introduced a mandatory IL course entitled Library and Information Services coded PGS-501 for Post Graduate Studies. Some 20% state universities have now introduced IL as essential part of curricula after CAR. The study also points out the need for innovative perspective in mode of delivering educational content engaging greater online or e- learning experiences.
Discuses situation of Library Legislation and Development of Library and Information Centers in I... more Discuses situation of Library Legislation and Development of Library and Information Centers in India, challenges and opportunities , role of national knowledge commission etc.
Free radical biology & medicine, Jan 7, 2015
Excess circulating iron is stored in the liver, and requires reduction of non-Tf-bound-iron (NTBI... more Excess circulating iron is stored in the liver, and requires reduction of non-Tf-bound-iron (NTBI) and transferrin (Tf)-iron at the plasma membrane and endosomes respectively by ferrireductase (FR) proteins for transport across biological membranes through divalent metal transporters. Here, we report that prion-protein (PrP(C)), a ubiquitously expressed glycoprotein most abundant on neuronal cells, functions as a FR partner for divalent-metal transporter-1 (DMT1) and ZIP14. Thus, absence of PrP(C) in PrP-knock-out (PrP(-/-)) mice resulted in markedly reduced liver iron stores, a deficiency that was not corrected by chronic or acute administration of iron by the oral or intra-peritoneal routes. Likewise, preferential radiolabeling of circulating NTBI with (59)Fe revealed significantly reduced uptake and storage of NTBI by the liver of PrP(-/-) mice relative to matched PrP(+/+) controls. However, uptake, storage, and utilization of ferritin-bound iron that does not require reduction f...
Journal of Alzheimer's disease : JAD, 2003
Although familial prion disorders are a direct consequence of mutations in the prion protein gene... more Although familial prion disorders are a direct consequence of mutations in the prion protein gene, the underlying mechanisms leading to neurodegeneration remain unclear. Potential pathogenic mechanisms include abnormal cellular metabolism of the mutant prion protein (PrP(M)), or destabilization of PrP(M) structure inducing a change in its conformation to the pathogenic PrP-scrapie (PrP(Sc)) form. To further clarify these mechanisms, we investigated the biogenesis of mutant PrP V203I and E211Q associated with Creutzfeldt-Jakob disease, and PrP Q212P associated with Gerstmann-Straussler-Scheinker syndrome in neuroblastoma cells. We report that all three PrP(M) forms accumulate similarly in the cytosol in response to proteasomal inhibition, and finally assemble as classical aggresomes. Since the three PrP(M) forms tested in this report are distinct, we propose that sequestration of misfolded PrP(M) into aggresomes is likely a general response of the cellular quality control that is not...
Discusses LIS course content followed by 17 universities of agricultural sciences in the country.... more Discusses LIS course content followed by 17 universities of agricultural sciences in the country. Analyses the suitability of these courses in achieving the objectives laid down and evaluates the course content in changing context and the need for restructuring the course curricula in present context. Suggests a separate one credit course on LIS user education and a separate course on technical writing.
Journal of Alzheimer's disease : JAD, 2013
Prion protein (PrPC) is implicated in the pathogenesis of prion disorders, but its normal functio... more Prion protein (PrPC) is implicated in the pathogenesis of prion disorders, but its normal function is unclear. We demonstrate that PrPC is a ferrireductase (FR), and its absence causes systemic iron deficiency in PrP knock-out mice (PrP-/-). When exposed to non-transferrin-bound (NTB) radioactive-iron (59FeCl3) by gastric-gavage, PrP-/- mice absorb significantly more 59Fe from the intestinal lumen relative to controls, indicating appropriate systemic response to the iron deficiency. Chronic exposure to excess dietary iron corrects this deficiency, but unlike wild-type (PrP+/+) controls that remain iron over-loaded, PrP-/- mice revert back to the iron deficient phenotype after 5 months of chase on normal diet. Bone marrow (BM) preparations of PrP-/- mice on normal diet show relatively less stainable iron, and this phenotype is only partially corrected by intraperitoneal administration of excess iron-dextran. Cultured PrP-/- BM-macrophages incorporate significantly less NTB-59Fe in th...
Journal of Neuroscience, 2004
Foodborne transmission of bovine spongiform encephalopathy (BSE) to humans as variant Creutzfeldt... more Foodborne transmission of bovine spongiform encephalopathy (BSE) to humans as variant Creutzfeldt-Jakob disease (CJD) has affected over 100 individuals, and probably millions of others have been exposed to BSE-contaminated food substances. Despite these obvious public health concerns, surprisingly little is known about the mechanism by which PrP-scrapie (PrP(Sc)), the most reliable surrogate marker of infection in BSE-contaminated food, crosses the human intestinal epithelial cell barrier. Here we show that digestive enzyme (DE) treatment of sporadic CJD brain homogenate generates a C-terminal fragment similar to the proteinase K-resistant PrP(Sc) core of 27-30 kDa implicated in prion disease transmission and pathogenesis. Notably, DE treatment results in a PrP(Sc)-protein complex that is avidly transcytosed in vesicular structures across an in vitro model of the human intestinal epithelial cell barrier, regardless of the amount of endogenous PrP(C) expression. Unexpectedly, PrP(Sc) is cotransported with ferritin, a prominent component of the DE-treated PrP(Sc)-protein complex. The transport of PrP(Sc)-ferritin is sensitive to low temperature, brefeldin-A, and nocodazole treatment and is inhibited by excess free ferritin, implicating a receptor- or transporter-mediated pathway. Because ferritin shares considerable homology across species, these data suggest that PrP(Sc)-associated proteins, in particular ferritin, may facilitate PrP(Sc) uptake in the intestine from distant species, leading to a carrier state in humans.
Libri, 2000
Information technology has brought a tremendous change in the nature, boundaries and structure of... more Information technology has brought a tremendous change in the nature, boundaries and structure of information. The ongoing movement towards an electronic information society is pushing libraries towards automation and digitization. The revolution has brought impressive changes in the role of LIS professionals who are now being viewed as information managers/facilitators. These developments have also influenced LIS writings and publishing. This study shows that while the application of IT has gained considerable importance in Indian libraries, IT-based papers have surprisingly found less space in Indian LIS periodicals as compared to the LIS literature in general. The findings of this study also indicate that there is an uneven distribution of various topics within the Indian LIS ITpublished literature; while some topics/areas of IT have received considerable attention others have been barely touched. Topics like IT in general, bibliographic databases, library networking, library automation and electronic resources have been found to predominate in the growth of Indian LIS literature as compared to the coverage of other areas of IT. Most papers (60 %) have single authors, indicating a low amount of teamwork/collaborative writing. The paper's analysis also reveals that working professionals/librarians have made more contributions (48%) in comparison to teaching professionals (22%).
Journal of Biological Chemistry, 2002
A familial prion disorder with a proline to leucine substitution at residue 102 of the prion prot... more A familial prion disorder with a proline to leucine substitution at residue 102 of the prion protein (PrP 102L ) is typically associated with protease-resistant PrP fragments (PrP Sc ) in the brain parenchyma that are infectious to recipient animals. When modeled in transgenic mice, a fatal neurodegenerative disease develops, but, unlike the human counterpart, PrP Sc is lacking and transmission to recipient animals is questionable. Alternate mice expressing a single copy of PrP 102L (mouse PrP 101L ) do not develop spontaneous disease, but show dramatic susceptibility to PrP Sc isolates from different species. To understand these discrepant results, we studied the biogenesis of human PrP 102L in a cell model. Here, we report that cells expressing PrP 102L show decreased expression of the normal 18-kDa fragment on the plasma membrane. Instead, a 20-kDa fragment, probably derived from transmembrane PrP ( Ctm PrP), accumulates on the cell surface. Because the 20-kDa fragment includes an amyloidogenic region of PrP that is disrupted in the 18-kDa form, increased surface expression of 20-kDa fragment may enhance the susceptibility of these cells to PrP Sc infection by providing an optimal substrate, or by amplifying the neurotoxic signal of PrP Sc . Thus, altered susceptibility of PrP 101L mice to exogenous PrP Sc may be mediated by the 20-kDa Ctm PrP fragment, rather than PrP 102L per se.
Journal of Biological Chemistry, 2010
Filamin A (FLNA) is an integrator of cell mechanics and signaling. The spreading and migration ob... more Filamin A (FLNA) is an integrator of cell mechanics and signaling. The spreading and migration observed in FLNA sufficient A7 melanoma cells but not in the parental FLNA deficient M2 cells have been attributed to FLNA. In A7 and M2 cells, the normal prion (PrP) exists as pro-PrP, retaining its glycosylphosphatidyl-inositol (GPI) anchor peptide signal sequence (GPI-PSS). The GPI-PSS of PrP has a FLNA binding motif and binds FLNA. Reducing PrP expression in A7 cells alters the spatial distribution of FLNA and organization of actin and diminishes cell spreading and migration. Integrin β1 also binds FLNA. In A7 cells, FLNA, PrP, and integrin β1 exist as two independent, yet functionally linked, complexes; they are FLNA with PrP or FLNA with integrin β1. Reducing PrP expression in A7 cells decreases the amount of integrin β1 bound to FLNA. A PrP GPI-PSS synthetic peptide that crosses the cell membrane inhibits A7 cell spreading and migration. Thus, in A7 cells FLNA does not act alone; the binding of pro-PrP enhances association between FLNA and integrin β1, which then promotes cell spreading and migration. Pro-PrP is detected in melanoma in situ but not in melanocyte. Invasive melanoma has more pro-PrP. The binding of pro-PrP to FLNA, therefore, contributes to melanomagenesis.
Frontiers in Bioscience, 2002
Prion diseases or transmissible spongiform encephalopathies are neurodegenerative disorders that ... more Prion diseases or transmissible spongiform encephalopathies are neurodegenerative disorders that are genetic, sporadic, or infectious. The pathogenetic event common to all prion disorders is a change in conformation of the cellular prion protein (PrPC) to the scrapie isoform (PrPSc), which, unlike PrPC, aggregates easily and is partially resistant to protease digestion. Although PrPSc is believed to be essential for the pathogenesis and transmission of prion disorders, the mechanism by which PrPSc deposits cause neurodegeneration is unclear. It has been proposed that in some cases of prion disorders, a transmembrane form of PrP, termed CtmPrP may be the mediator of neurodegenerative changes rather than PrPSc per se. In order to understand the underlying cellular processes by which PrPSc mediates neurodegeneration, we have investigated the mechanism of neurotoxicity by a beta-sheet rich peptide of PrP in a cell model. We show that exposure of human neuronal cell lines NT-2 and M17 to the prion peptide 106-126 (PrP106-126) catalyzes the aggregation of endogenous cellular prion protein (PrPC) to an amyloidogenic form that shares several characteristics with PrPSc. Intracellular accumulation of these PrPSc-like forms upregulates the synthesis of CtmPrP, which is proteolytically cleaved in the endoplasmic reticulum and the truncated C-terminal fragment is transported to the cell surface. In addition, we have isolated mutant NT-2 and neuroblastoma cells that are resistant to toxicity by PrP106-126 to facilitate further characterization of the biochemical pathways of PrP106-126 neurotoxicity. The PrP106-126-resistant phenotype of these cells could result from aberrant binding or internalization of the peptide, or due to an abnormality in the downstream pathway(s) of neuronal toxicity. Thus, our data suggest that PrPSc aggregation occurs by a process of &amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;#39;nucleation&amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;#39; on a pre-existing &amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;#39;seed&amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;#39; of PrP. Furthermore, the PrP106-126-resistant cells reported here will provide a unique opportunity for identifying the cellular and biochemical pathways that mediate neurotoxicity by PrPSc.
Molecular Brain Research, 2004
Familial Creutzfeldt -Jakob disease (CJD) comprises a group of neurodegenerative disorders for wh... more Familial Creutzfeldt -Jakob disease (CJD) comprises a group of neurodegenerative disorders for which currently there is no treatment. In this study, we evaluated the efficacy of drugs approved for human use, and protein folding agents in reversing the mutant phenotype of familial CJD H187R in a cell model. For an efficient experimental readout, green fluorescent protein (GFP)-tagged mutant prion protein (PrP 187R-GFP ) and wild-type PrP (PrP C-GFP ) were expressed in human neuroblastoma cells. We report that unlike PrP C-GFP that is expressed on the cell surface, PrP 187R-GFP accumulates in the lysosomes of transfected cells. Treatment of PrP 187R-GFP cells with quinacrine or doxycycline, agents known to inhibit the replication of PrP-scrapie (PrP Sc ) in experimental models, gave conflicting results; doxycycline reverted the mutant phenotype of PrP 187R-GFP cells, whereas quinacrine had no effect. The concentration of doxycycline used in these studies is well within the plasma concentration of patients receiving a 250 -600 mg dose two to three times daily. Interestingly, exposure of PrP 187R-GFP cells to low temperature (28jC) or to the chemical chaperones dimethyl sulphoxide (DMSO) and glycerol also reversed the mutant phenotype. These data suggest that doxycycline and protein folding agents may hold promise as therapeutic agents for familial CJD H187R and other familial disorders that share similar pathogenic mechanisms. D
Antioxidants & Redox Signaling, 2013
Aims: Most biomarkers used for the premortem diagnosis of sporadic Creutzfeldt-Jakob disease (CJD... more Aims: Most biomarkers used for the premortem diagnosis of sporadic Creutzfeldt-Jakob disease (CJD) are surrogate in nature, and provide suboptimal sensitivity and specificity. Results: We report that CJD-associated brain iron dyshomeostasis is reflected in the cerebrospinal fluid (CSF), providing disease-specific diagnostic biomarkers. Analysis of 290 premortem CSF samples from confirmed cases of CJD, Alzheimer's disease, and other dementias (DMs), and 52 non-DM (ND) controls revealed a significant difference in ferroxidase (Frx) activity and transferrin (Tf) levels in sporadic Creutzfeldt-Jakob disease (sCJD) relative to other DM and ND controls. A combination of CSF Frx and Tf discriminated sCJD from other DMs with a sensitivity of 86.8%, specificity of 92.5%, accuracy of 88.9%, and area-under-the receiver-operating-characteristic (ROC) curve of 0.94. This combination provided a similar diagnostic accuracy in discriminating CJD from rapidly progressing cases who died within 6 months of sample collection. Surprisingly, ceruloplasmin and amyloid precursor protein, the major brain Frxs, displayed minimal activity in the CSF. Most of the Frx activity was concentrated in the < 3-kDa fraction in normal and diseased CSF, and resisted heat and proteinase-K treatment. Innovation: (i) A combination of CSF Frx and Tf provides disease-specific premortem diagnostic biomarkers for sCJD. (ii) A novel, nonenzymatic, nonprotein Frx predominates in human CSF that is distinct from the currently known CSF Frxs. Conclusion: The underlying cause of iron imbalance is distinct in sCJD relative to other DMs associated with the brain iron imbalance. Thus, change in the CSF levels of iron-management proteins can provide disease-specific biomarkers and insight into the cause of iron imbalance in neurodegenerative conditions.
Prion disease associated neurotoxicity is mainly attributed to PrP-scrapie (PrP Sc ), the disease... more Prion disease associated neurotoxicity is mainly attributed to PrP-scrapie (PrP Sc ), the disease associated isoform of a normal protein, the prion protein (PrP C ). Participation of other proteins and processes is suspected, but their identity and contribution to the pathogenic process is unclear. Emerging evidence implicates imbalance of brain iron homeostasis as a significant cause of prion disease-associated neurotoxicity. The underlying cause of this change, however, remains unclear. We demonstrate that iron is sequestered in heat and SDS-stable protein complexes in sporadic-Creutzfeldt-Jakob-disease (sCJD) brains, creating a phenotype of iron deficiency. The underlying cause is change in the characteristics of ferritin, an iron storage protein that becomes aggregated, detergent-insoluble, and partitions with denatured ferritin using conventional methods of ferritin purification. A similar phenotype of iron deficiency is noted in the lumbar spinal cord (SC) tissue of scrapie infected hamsters, a site unlikely to be affected by massive neuronal death and nonspecific iron deposition. As a result, the iron uptake protein transferrin (Tf) is upregulated in scrapie infected SC tissue, and increases with disease progression. A direct correlation between Tf and PrP Sc suggests sequestration of iron in dysfunctional ferritin that either co-aggregates with PrP Sc or is rendered dysfunctional by PrP Sc through an indirect process. Surprisingly, amplification of PrP Sc in vitro by the protein-misfolding-cyclic-amplification (PMCA) reaction using normal brain homogenate as substrate does not increase the heat and SDS-stable pool of iron even though both PrP Sc and ferritin aggregate by this procedure. These observations highlight important differences between PrP Sc -protein complexes generated in vivo during disease progression and in vitro by the PMCA reaction, and the significance of these complexes in PrP Scassociated neurotoxicity.
The Electronic Library, 2014
e article explores how Indian Agricultural libraries have evolved and transformed in the digital... more e article explores how Indian Agricultural libraries have evolved and transformed in the digital era and how technological advances and increased sophistication of web based tools have enabled libraries to collaborate and share resources. e authors identify various innovative practices adopted by fiy six Indian agricultural libraries and detail the collaborative county-wide programs and digitization projects in progress such as eGranth's AgriCat, a union catalog of books and articles in agriculture and allied sciences. Also described are activities involving digital institutional repositories like KrishiKosh and KrishiPrabha and the establishment of a national level consortium for e-journals and digital content accessible to the Indian academic community. Grants from World Bank-ICAR funded projects like the National Agricultural Innovative Project (NAIP) have boosted digitization in India and have brought libraries and the user community into closer proximity virtually by removing physical boundaries. Resumé: L'article explore comment les bibliothèques agricoles indiennes ont évolué et se sont transformées sous l'ère nu mérique, et comment les progrès technologiques et la sophistication croissante des instruments du web ont permis aux bibliothèques de collaborer et de partager les ressources. Les auteurs identifient diverses pratiques novatrices adoptées par cin quantesix bibliothèques agricoles indiennes, et détaillent les programmes de collaboration et projets de numérisation en cours au niveau des comtés comme la eGranth AgriCat, un catalogue de livres et d'articles dans les domaines de l'agriculture et des sciences alliées. D'autres activités numériques sont aussi dé crites tels les dépôts institutionnels comme KrishiKosh et KrishiPrabha, et l'établissement d'un consortium au niveau national pour l'accès aux e-revues et au contenu numérique, par la communauté universitaire indienne. Des subventions venant de projets financés par la Banque mondiale-ICAR comme le Projet national d'agriculture novatrice (NAIP) ont stimulé la numérisation en Inde, et rapproché étroitement les bibliothèques et la communauté des utilisateurs pratiquement en supprimant les frontières physiques.
Information Literacy is receiving increasing attention among Indian professional practice with em... more Information Literacy is receiving increasing attention among Indian professional practice with emergence of electronic resources and digitization activities in libraries. As early as 1970's User instruction existed in Indian agricultural universities and were adapted from US land Grant pattern universities. Formally popularly known as User education, most universities had an embedded curriculum approach to enhance students information and research skills . This study investigates and analyses what agricultural universities are offering to enhance their students library or information skills. In addition, identifies basic contents in terms of latest developments, library skills and research skills, approach to uniformity, concept like subject librarian.Findings reveal that out of 34 universities surveyed , significantly high more than 90.0 % offer credit bearing information literacy through curriculum approach by different names, to mention a few like Research Methodology and Library Use, Technical writing and User Education, Storage and Retrieval of Scientific Information, Agricultural Information system etc. Most state universities provide such course to Graduate students and are yet to introduce structured courses for under graduates. In the year 2010 the Indian Council of Agricultural Research formulated Common Academic Regulations (CAR) and introduced a mandatory IL course entitled Library and Information Services coded PGS-501 for Post Graduate Studies. Some 20% state universities have now introduced IL as essential part of curricula after CAR. The study also points out the need for innovative perspective in mode of delivering educational content engaging greater online or e-learning experiences.
The study describes information seeking of farmers’ communities in the Himalayan state of Uttrakh... more The study describes information seeking of farmers’ communities in the Himalayan state of Uttrakhand in
India. The work reveals that there is a growing awareness among the farmers of this state and adjoining
states. 4266 queries were received by G B Pant University of Agriculture and Technology’s telecenter and
farmers helpline in the period of 2006 -2008. Farmers sought most information from the toll free telecenter
popularly known as Kissan (farmers) reference to the Information Center and use of the telecenter helpline
was found to be substantially less.The telecenters function on 3 levels. Findings reveal that most
information sought by farmers was provided in the local language by level I experts, who are Agricultural
Science Graduates. Level II involves specific queries answered by subject specialists. The Helpline of
universities functions at level II, where farmers can directly seek information from subject experts.
Maximum information was sought in the month of September followed by October and November. These
months are crucial for Rainy and Winter season crops, therefore requiring maximum attention of farmers in
protecting their standing rainfed crops and planning winter crops. 1252 queries were received during 2006
on various subjects, which gradually increased to 1315 in 2007 and 1721 queries in 2008. Most information
was sought on subjects like Agronomy and farmers’ fairs. Substantial information was also sought on plant
diseases,cultivation of vegetables, and seeds availability. Subject like solar energy, crop insurance, and silk
production have been found to be the least popular among the farming community. The study further
indicates that most information was sought on crops that provided quick cash rather than complicated
subject like use of solar energy or silk production. Most farmers in India are involved in small or marginal
farming, therefore prefer growing cash-crops as a source of income for their livelihood.
Information Literacy is receiving increasing attention among Indian professional practice with e... more Information Literacy is receiving increasing attention among Indian professional practice with emergence of electronic resources and digitization activities in libraries. As early as 1970’s User instruction existed in Indian agricultural universities and were adapted from US land Grant pattern universities. Formally popularly known as User education, most universities had an embedded curriculum approach to enhance students information and research skills . This study investigates and analyses what agricultural universities are offering to enhance their students library or information skills. In addition, identifies basic contents in terms of latest developments, library skills and research skills, approach to uniformity, concept like subject librarian.
Findings reveals that out of 34 universities surveyed , significantly high more than 90.0 % offer credit bearing information literacy through curriculum approach by different names, to mention a few like Research Methodology and Library Use, Technical writing and User Education, Storage and Retrieval of Scientific Information, Agricultural Information system etc. Most state universities provide such course to Graduate students and are yet to introduce structured courses for under graduates. In the year 2010 the Indian Council of Agricultural Research formulated Common Academic Regulations (CAR) and introduced a mandatory IL course entitled Library and Information Services coded PGS-501 for Post Graduate Studies. Some 20% state universities have now introduced IL as essential part of curricula after CAR. The study also points out the need for innovative perspective in mode of delivering educational content engaging greater online or e- learning experiences.
The trend of digital repositories, union catalogues, digital platform for collaborative networkin... more The trend of digital repositories, union catalogues, digital platform for collaborative networking and resource sharing has become increasing important and more relevant today among Indian agricultural libraries. Libraries are exploring new ways to fulfill the information requirement of their patrons through resource sharing and document delivery using the online platform accessible everywhere. The article discusses Inter Library Loan and Document Delivery Services (DDR) facilitated through Consortium Journal Gateway in collaboration with 134 member agricultural libraries under Indian National Agricultural Research System. CeRA the (Consortium for e-Resources in Agriculture) provides a platform for online access to e-journals and inter Library Loan. DDR Services has been established to share resources subscribed by individual libraries as well as consortium journals using the web portal of CeRA. The article also presents an interesting case study of the use of DDR services by patrons of the first Indian Agricultural University that played a vital role in bringing a green revolution in the country.