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Distribution by Scientific Domains

Medical Sciences	40%

Selected Abstracts

New developments in small molecules targeting p53 pathways in anticancer therapy

DRUG DEVELOPMENT RESEARCH, Issue 6 2008
Chit Fang Cheok
Abstract The tumor suppressor p53 is frequently inactivated in a wide variety of cancers and point mutations or deletions of the p53 gene are associated with poor prognosis in cancer. About half of all human tumors carry wildtype p53 but p53 wildtype functions are often suppressed by the overexpression of murine double minute 2 (MDM2), a negative regulator of p53. Restoration of p53 functions in tumor cells, therefore, represents an attractive strategy in combating cancer and has been the focus of intensive anticancer drug discovery. One strategy is to antagonize MDM2 functions and initial success was demonstrated in vitro and in xenograft tumor models using newly discovered small molecule inhibitors and antisense oligonucleotides. The new discovery of a compound targeting SirT1 (a member of the sirtuin family) in a p53-dependent reporter screen highlighted the importance of another negative regulator of p53 and offers an additional avenue for drug discovery and research on p53-activating therapeutics. Here, we discuss the developments of p53-activating small molecules and their potential use in combination therapy with established chemotherapeutics. These small molecules were discovered from chemical library screening using biochemical assays or cellular-based assays, and/or structure-based rational drug design strategies. Drug Dev Res 69:289,296, 2008. © 2008 Wiley-Liss, Inc. [source]

Application of capillary electrophoresis mass spectrometry to the characterization of bacterial lipopolysaccharides

MASS SPECTROMETRY REVIEWS, Issue 1 2007
Jianjun Li
Abstract Capillary electrophoresis (CE) is a high-resolution technique for the separation of complex biological mixtures and has been widely applied to biological analyses. The coupling of capillary electrophoresis with mass spectrometry (MS) provides a powerful approach for rapid identification of target analytes present at trace levels in biological matrices, and for structural characterization of complex biomolecules. Here we review the analytical potential of combined capillary electrophoresis electrospray mass spectrometry (CE-MS) for the analysis of bacterial lipopolysaccharides (LPS). This hyphened methodology facilitates the determination of closely related LPS glycoform and isoform families by exploiting differences in their unique molecular conformations and ionic charge distributions by electrophoretic separation. On-line CE-MS also provides an additional avenue to improve detection limits, which has been successfully applied to directly probe oligosaccharide LPS glycoform populations of bacteria isolated from infected animal models without the need for further passage. © 2006 Wiley Periodicals, Inc., Mass Spec Rev 26:35,50, 2007 [source]

Governing by Managing Identity Boundaries: The Case of Family Businesses

ENTREPRENEURSHIP THEORY AND PRACTICE, Issue 3 2008
Chamu Sundaramurthy
In this paper we illustrate how boundary theory can be a useful perspective to understand the dynamics of family businesses. We integrate insights from the family business literature with the work,family and identity boundary literatures to describe degrees of integration between the family and business identities in family firms and outline contingencies that influence this integration. We also develop the notion of "differential permeability" as a state of being both integrated and segmented on various aspects of identity and articulate costs and benefits to this state, as well as to high integration and high segmentation. Finally, we invoke the research on "boundary work" as a means of managing family business boundaries and conclude by outlining additional avenues of research that stem from using such a boundary theory lens. [source]

Modeling Socioeconomic Class in Variationist Sociolinguistics

LINGUISTICS & LANGUAGE COMPASS (ELECTRONIC), Issue 5 2009
Robin Dodsworth
Modeling socioeconomic class has been a persistent challenge in the analysis of sociolinguistic variation. While early stratificational models formulated on the basis of socioeconomic indicators such as income, occupation, and area of residence revealed compelling patterns of linguistic variation, they were critiqued for their lack of explanatory power at the interactional level and for their marginalization of those without paid employment. Subsequent models have employed cross-disciplinary concepts such as the linguistic market, social networks, and communities of practice, prioritizing local social distinctions that are understood to reflect or even constitute abstract structural categories such as ,working class' or ,middle class'. It is argued that a full socioeconomic class paradigm for sociolinguistics would also theorize class at the aggregate level, and to this end, sociological class models may prove useful. Contemporary sociological class analysis at the level of social practice offers additional avenues for interfacing with sociology. [source]

Maternal Transmission of Nicotine Dependence: Psychiatric, Neurocognitive and Prenatal Factors

THE AMERICAN JOURNAL ON ADDICTIONS, Issue 1 2001
Raymond Niaura Ph.D.
This paper reviews the literature on maternal influences on smoking behaviors of offspring from the perspective of neuropsychiatric deficits that may be transmitted from mother to child. In particular, we review what is known regarding associations between: (1) in-utero exposure to smoking, (2) adolescent neurocognitive functioning and psychiatric comorbidity, and (3) the patterns of smoking and progression of nicotine dependence. Furthering our knowledge of these differences in susceptibility to nicotine dependence among youth will provide additional avenues for prevention and intervention efforts targeted toward those at high risk for dependence. [source]