Studies of the lamin proteinase reveal multiple parallel biochemical pathways during apoptotic execution.

Although specific proteinases play a critical role in the active phase of apoptosis, their substrates are largely unknown. We previously identified poly(ADP-ribose) polymerase (PARP) as an apoptosis-associated substrate for proteinase(s) related to interleukin 1 beta-converting enzyme (ICE). Now we have used a cell-free system to characterize proteinase(s) that cleave the nuclear lamins during apoptosis. Lamin cleavage during apoptosis requires the action of a second ICE-like enyzme, which exhibits kinetics of cleavage and a profile of sensitivity to specific inhibitors that is distinct from the PARP proteinase. Thus, multiple ICE-like enzymes are required for apoptotic events in these cell-free extracts. Inhibition of the lamin proteinase with tosyllysine "chloromethyl ketone" blocks nuclear apoptosis prior to the packaging of condensed chromatin into apoptotic bodies. Under these conditions, the nuclear DNA is fully cleaved to a nucleosomal ladder. Our studies reveal that the lamin proteinase and the fragmentation nuclease function in independent parallel pathways during the final stages of apoptotic execution. Neither pathway alone is sufficient for completion of nuclear apoptosis. Instead, the various activities cooperate to drive the disassembly of the nucleus.

Identification of an 11-kDa FKBP12-rapamycin-binding domain within the 289-kDa FKBP12-rapamycin-associated protein and characterization of a critical serine residue.

Complexed with its intracellular receptor, FKBP12, the natural product rapamycin inhibits G1 progression of the cell cycle in a variety of mammalian cell lines and in the yeast Saccharomyces cerevisae. Previously, a mammalian protein that directly associates with FKBP12-rapamycin has been identified and its encoding gene has been cloned from both human (designated FRAP) [Brown, E.J., Albers, M.W., Shin, T.B., Ichikawa, K., Keith, C.T., Lane, W.S. & Schreiber, S.L. (1994) Nature (London) 369, 756-758] and rat (designated RAFT) [Sabatini, D.M., Erdjument-Bromage, H., Lui, M., Tempst, P. & Snyder, S.H. (1994) Cell 78, 35-43]. The full-length FRAP is a 289-kDa protein containing a putative phosphatidylinositol kinase domain. Using an in vitro transcription/translation assay method coupled with proteolysis studies, we have identified an 11-kDa FKBP12-rapamycin-binding domain within FRAP. This minimal binding domain lies N-terminal to the kinase domain and spans residues 2025-2114. In addition, we have carried out mutagenesis studies to investigate the role of Ser2035, a potential phosphorylation site for protein kinase C within this domain. We now show that the FRAP Ser2035-->Ala mutant displays similar binding affinity when compared with the wild-type protein, whereas all other mutations at this site, including mimics of phosphoserine, abolish binding, presumably due to either unfavorable steric interactions or induced conformational changes.

Evolution of Melanocortin-2 Receptor Activations: Studies on a Mammal and a Fish

The structure and function relationship between melanocortin-2 receptor (MC2R) and ACTH are the most complicated in melanocortin receptor gene family. A comparative study on the activation of human and rainbow trout MC2R will provide a useful model system for understanding how ACTH emerged as the sole ligand for the MC2R of bony vertebrates. This dissertation will discuss how studies utilizing analogs of hACTH(1-24) have revealed two critical amino acid motifs in this ligand (HFRW and KKRRP) which are required for the activation of MC2R. In addition, the KKRRP motif functioned as the unique binding site for MC2R that directly contributes to the ligand selectivity feature, as revealed from studies on an ACTH antagonist which exclusively targets MC2R. Finally, based on our model for the interaction of ACTH and MC2R, the amino acid residues within TM4, EC2, and TM5 domains responsible for ACTH ligand selectivity will be evaluated by site-directed mutagenesis studies.

What We Are Learning About the Diverse Backgrounds of Academic Library Users: An Overview of Research Designs and Methods in Information Behaviour Studies

Academic libraries increasingly serve a more diverse population of users not only in regard to race and ethnicity, but also to age, gender, language, sexual orientation, and national and cultural backgrounds. This papers reports the findings of the study that explored information behaviour research as a potential source of information about diversity of academic library users and examined the relationship between the use of different research designs and data collection methods and the information gathered about users’ diverse backgrounds. The study found that information behaviour research offers limited insight into the diversity of academic library users. The choice of a research design was not critical but the use of multiple data collection played a role in gathering information about culturally diverse users.

Critical review of the bibliography on the History of Translation in Spain

This article is the English version of “Examen crítico de la bibliografía sobre la historia de la traducción en España” by David Pérez Blázquez. It was not published on the print version of MonTI for reasons of space. The online version of MonTI does not suffer from these limitations, and this is our way of promoting plurilingualism.

The place of DPP-4 inhibitors in the treatment algorithm of diabetes type 2 : a systematic review of cost-effectiveness studies

Tese de mestrado, Epidemiologia, Universidade de Lisboa, Faculdade de Medicina, 2015

Global Solutions, Local Damages: A Critical Study in Judicial Councils in Central and Eastern Europe. Research Paper in Law 07/2013

This article examines why, how, and with what results have judicial councils spread under the influence of European institutions throughout Central and Eastern Europe in the course of the last twenty years. It first traces back how the judicial councils, themselves just one possible form of administration of courts, have emerged as the recommended universal solution Europe-wide and internationally. Second, it discusses how has this model been exported under the patronage of European and international institutions to transition countries in Central and Eastern Europe. Assessing, thirdly, the reality of the functioning of such new judicial councils in these countries, in particular in Slovakia and Hungary, with the Czech Republic without a judicial council providing a counter-example, it is suggested that their impact on further judicial and legal transition has been either questionable or outright disastrous. This brings, eventually, into question the legitimacy as well as the bare reasonableness of the entire process of European/international standards setting and their later marketing or in reality rather imposition onto the countries in transition.

An empirical interpretation of annuli critical mass data /

"U.S. Atomic Energy Commission Contract AT(29-1)-1106."

Short studies on great subjects /

"This volume forms the second series of Froude's Short studies, as reprinted in Everyman's library. The first volume, originally issued in the series with the title Essays in literature and history, contains a general introduction by M. Belloc to Froude's work and critical attitude in the Short studies."--v. 2, p. vii.

Dalit Studies /

Analyzes the role of Dalits (formerly untouchables) in shaping modern India, including discourse about caste, and interrogates the dominant narratives that have been used to represent India's history. This title was made Open Access by libraries from around the world through Knowledge Unlatched.

An easy introduction to the game of chess; containing one hundred examples of games, and a great variety of critical situations and conclusions, including the whole of Philidor's analysis, with selections from Stamma, the Calabrois, &c, to which are added, Caissa, a poem,

Based on Pratt's Studies of chess.

Studies of Irving,

Added imprint stamped on t.p. : London, Trübner.

Developing students' critical literacy: Exploring identity construction in young adult fiction

The authors use a critical literacy stance to engage students in a discussion of young adult literature from Australia and America. They offer a framework teachers can use to initiate discussions based on critical literacy in their own classrooms.