Checkpoint Regulation of S-Phase Transcription: A Dissertation

The DNA replication checkpoint transcriptionally up-regulates genes that allow cells to adapt to and survive replication stress. Our results show that, in the fission yeast Schizosaccharomyces pombe, the replication checkpoint regulates the entire G1/S transcriptional program by directly regulating MBF (aka DSC1), the G1/S transcription factor. Instead of initiating a checkpoint-specific transcriptional program, the replication checkpoint targets MBF to maintain the normal G1/S transcriptional program during replication stress. We propose a mechanism for this regulation, based on in vitrophosphorylation of the Cdc10 subunit of MBF by the Cds1 replication-checkpoint kinase. Substitution of two potential phosphorylation sites with phospho-mimetic amino acids suffice to promote the checkpoint transcriptional program, suggesting that Cds1 phosphorylation directly regulates MBF-dependent transcription. The conservation of MBF between fission and budding yeast, and recent results implicating MBF as a target of the budding yeast replication checkpoint, suggest that checkpoint regulation of the MBF transcription factor may be a conserved strategy for coping with replication stress. Furthermore, the structural and regulatory similarity between MBF and E2F, the metazoan G1/S transcription factor, suggests that this checkpoint mechanism may be broadly conserved among eukaryotes. Our result shows that both the replication checkpoint and the S-phase DNA damage checkpoint are involved in activating MBF regulated S-phase gene transcription and that this coordinated transcriptional response is beneficial for survival during replication stress. I demonstrate that the beneficial role of the transcriptional response during checkpoint activation is mediated by three major MBF transcripts: cdc22, mrc1 and mik1. Mrc1 dependent stabilization of stalled fork is important during S phase arrest. However, cells ability to prevent mitosis (Mik1 dependent) along with stable fork (Mrc1 dependent) both are crucial for survival. Our data also suggest that the level of Cdc22 is a determining factor for replication checkpoint activation and when over-expressed can alleviate the effects not only in HU but also in MMS

A linguistic view of subject formation process as described by Ranganathan andothers

The basic implication of a subject in the context of library and information science is outlined here. It is pointed outthat the purview of library and information science mostly reckons any subject in the form of some either assigned orderived terms or keywords. The basic concepts of words as per the scope of linguistics are also provided. Different modes offormation of complex and compound subjects as enunciated by Ranganathan are described. The modes of formation ofcompound words as depicted in linguistics have been described and compared with different modes of formation of complexand compound subjects as portrayed by Ranganathan, Neelameghan, Seetharama and Sen. It has been observed that thereare similarities between modes of formation of words and subjects. As similarities are observed at the very basic foundationlevel between words and subjects, therefore it has been concluded that there may be some similarities of intrinsic propertiesbetween them. The specific words belonging to a particular subject domain or subject-specific words that are commonlyknown as keywords may thus be recognized as eventual denomination or fundamental building block of the concernedsubject. The keywords may thus be looked upon as molecule of a subject from linguistic viewpoint

The Role of Specific Checkpoint-Induced S-Phase Transcripts in Resistance to Replicative Stress

Checkpoint activation during S phase modulates transcription. In response to replication arrest, the fission yeast Cds1 checkpoint kinase maintains the normal S-phase transcriptional program by regulating MBF, the S-phase transcription factor. We show that similar regulation occurs in response to DNA damage during S-phase. We test the relative contributions to replication-stress resistance of transcriptional regulation and the two other major checkpoint functions: cell-cycle arrest and fork stabilization. We show that, although transcriptional regulation provides only modest resistance relative to fork stabilization, it contributes significantly to cell survival. Finally, we investigate the roles of two specific transcripts: mik1 and mrc1. These results demonstrate the general importance of checkpoint regulation of G1/S transcription in response to replicative stress and elucidate the specific roles of Mik1 and Mrc1 in the checkpoint

Toxoplasma gondii Induces Granulocyte Colony-Stimulating Factor and Granulocyte-Macrophage Colony-Stimulating Factor Secretion by Human Fibroblasts: Implications for Neutrophil Apoptosis

Human neutrophils are rescued from apoptosis following incubation with once-washed, fibroblast-derived Toxoplasma gondii tachyzoites. Both infected and uninfected neutrophils are rescued, implicating a soluble mediator. In this study we investigated the origin and identity of this soluble mediator. Neutrophils were incubated either with purified tachyzoites or with conditioned medium derived from T. gondii-infected human fibroblasts. Conditioned medium was found to be a potent stimulus that delayed neutrophil apoptosis up to 72 h, whereas purified and extensively washed tachyzoites had no effect. Delayed apoptosis correlated with up-regulation of the neutrophil antiapoptotic protein, Mcl-1, and the neutrophil interleukin 3 receptor alpha subunit (IL-3Ralpha), suggesting a role for granulocyte-macrophage colony-stimulating factor (GM-CSF). GM-CSF and granulocyte colony-stimulating factor (G-CSF) were measurable in conditioned medium by enzyme-linked immunosorbent assay. Neutralizing antibodies to GM-CSF and G-CSF were additive in abrogating delayed neutrophil apoptosis induced by conditioned medium. Inhibitors of Src family tyrosine kinases, G(i) proteins, phosphatidylinositol 3-kinase, p44(erk1) and p42(erk2) mitogen-activated protein kinases, and Jak2 kinases partially attenuated the effect of conditioned medium, consistent with a role for G-CSF and/or GM-CSF. Hence, delayed neutrophil apoptosis is mediated by GM-CSF and G-CSF secreted by T. gondii-infected human fibroblasts. This enhanced neutrophil survival may contribute to the robust proinflammatory response elicited in the T. gondii-infected host

The DNA damage and the DNA replication checkpoints converge at the MBF transcription factor

In fission yeast cells, Cds1 is the effector kinase of the DNA replication checkpoint. We previously showed that when the DNA replication checkpoint is activated, the repressor Yox1 is phosphorylated and inactivated by Cds1, resulting in activation of MluI-binding factor (MBF)-dependent transcription. This is essential to reinitiate DNA synthesis and for correct G1-to-S transition. Here we show that Cdc10, which is an essential part of the MBF core, is the target of the DNA damage checkpoint. When fission yeast cells are treated with DNA-damaging agents, Chk1 is activated and phosphorylates Cdc10 at its carboxy-terminal domain. This modification is responsible for the repression of MBF-dependent transcription through induced release of MBF from chromatin. This inactivation of MBF is important for survival of cells challenged with DNA-damaging agents. Thus Yox1 and Cdc10 couple normal cell cycle regulation in unperturbed conditions and the DNA replication and DNA damage checkpoints into a single transcriptional complex

Information Literacy Competency and Readership Study of Five Specific Localities in Urban, Industrial and Semi-Urban Areas of Kolkata Metropolitan City

The Department of Library and Information Science, Jadavpur University, Kolkata, India, in association with UNESCO, completed a research study to measure information literacy competency and reading habits amongst the urban and semi-urban habitats in a metropolitan city in India. This study report seeks to identify and critically examine the information literary competency and reading habits of mixed habitats, having contrasting professions or vocations. The objectives of this field study were: • To attempt a critical study of the readership of people from different social strata of five specific localities of Kolkata metropolitan city; • To attempt a study of the influence and to measure the encroachment of different media on people’s reading habit; • To attempt an assessment of the probable causes behind the difference in pattern of the reading habits of people in different localities of Kolkata metropolitan city; • To attempt an assessment of the role played by public libraries in promoting reading habits; • To attempt a mapping of the information literacy competency level of people living in Urban, Industrial and Semi-Urban areas of Kolkata metropolitan city; • To attempt to reach a viable conclusion from the results of the study. This report illustrates information seeking behaviour of diverse groups of habitats, including youths, women, industrial workers and elderly persons. This study concludes that • Most of the respondents in the present sample are aged between 31 and 50 and are in service. • The number of men who do not read regularly far exceeds the number of women in the same category. • Older people have mostly managed to cling on to their habit of reading. • Among the non-print media, television attracts most respondents. • Women are more prone to use libraries for satisfaction of their reading needs. • Reading still survives, despite the electronic media boom. The public libraries in the city play wider role to inculcate reading habits amongst youths and neo-literates. This study suggests that information literacy competency and lifelong education can also be imparted to marginalized group through public library networks in the country

Strengthening rural information infrastructure through e-Choupals

Apart from government and developmental agencies’ initiatives, rural information infrastructure develops in some parts of India through corporate initiatives. Some electronic information facilitation centers have been established to cater to the information needs of the farmers at their doorsteps in villages. One of them is e-Choupal system, conceived by the ITC Limited. It serves a dual purpose, as an Internet kiosk and as an alternative village mandi system. There are some pros and cons for this system as the company is interested in buying only those agricultural produces from the farmers, which can be processed into commodities having either a global market or a domestic market. Other agricultural produces are not covered here. Farmers get decision-making information from the information hub of an e-Choupal, and are able to decide their own. The company, having established e-Choupals in villages, recruits local youths as Sanchalaks and Samjojaks, and provides the requisite physical infrastructure for the functioning of the system

Concept of ‘subject’ in the context of library and information science from a new angle

The concept of subject as expounded in library and information science (LIS) has been interpreted here from the standpoint of the concept of word in linguistics. Both the concepts have been thoroughly reviewed. It has been observed that the concept of subject so long conceived by different researchers in LIS is basically preceded by the concept of document. The description of subject, therefore in most cases, by default becomes incumbent within the concept of document. Since the document is a macroscopic entity, therefore document-dependent description of subject naturally portrays a macroscopic layout of the same. This paper attempts to develop a document-independent description of subject, which is based on semantically-related words within the domain of appropriate context. According to this new description the subject would eventually become definable as sets of well-defined and semantically-related words that may be regarded as microscopic description. It has also been found out that the seed of document-independent and word-based definition of subject was already sown in the concept of semantic field, a domain under the subject linguistics. This concept was incepted by Trier and subsequently modified by Lehrer. It has been logically established that the idea of foci incepted by Ranganathan and the idea of semantic field incepted and modified by Trier and Lehrer respectively are conceptually equivalent. A subject may therefore be described as sets of semantic fields and, in turn as sets of words

Digitization of scholarly materials in India for distance and open learners

In India, a number of national level institutions are digitizing their own information resources and varieties of rare items. The Ministry of Communication and Information Technology has also established Digital Library of India Initiative. The digital libraries and institutional repositories in India include digitized collection of academic publications, like, dissertations, theses, research reports, working papers and research papers other than rare books and manuscripts. All these digitized materials can be made available and accessible to the learners of distance education. The distance and open learners should not be confined into the study materials provided to them and can explore the universe of knowledge through the digital libraries, institutional repositories and learning objects repositories available today. Present study explores the digital libraries and institutional repositories initiatives, programmes and projects in India that can be helpful to the distant and open learners. There is also need of establishing a national level learning objects repository for the benefits of open and distance learners and their tutors