Cysteine-10 on 17 β-Hydroxysteroid dehydrogenase 1 has stabilizing interactions in the cofactor binding region and renders sensitivity to sulfhydryl modifying chemicals

17 β-Hydroxysteroid dehydrogenase type 1 (17 β -HSD1) catalyzes the conversion of estrone to the potent estrogen estradiol. 17 β -HSD1 is highly expressed in breast and ovary tissues and represents a prognostic marker for the tumor progression and survival of patients with breast cancer and other estrogen-dependent tumors. Therefore, the enzyme is considered a promising drug target against estrogen-dependent cancers. For the development of novel inhibitors, an improved understanding of the structure-function relationships is essential. In the present study, we examined the role of a cysteine residue, Cys(10), in the Rossmann-fold NADPH binding region, for 17 β -HSD1 function and tested the sensitivity towards sulfhydryl modifying chemicals. 3D structure modeling revealed important interactions of Cys(10) with residues involved in the stabilization of amino acids of the NADPH binding pocket. Analysis of enzyme activity revealed that 17 β -HSD1 was irreversibly inhibited by the sulfhydryl modifying agents N-ethylmaleimide (NEM) and dithiocarbamates. Preincubation with increasing concentrations of NADPH protected 17 β -HSD1 from inhibition by these chemicals. Cys(10)Ser mutant 17 β -HSD1 was partially protected from inhibition by NEM and dithiocarbamates, emphasizing the importance of Cys(10) in the cofactor binding region. Substitution of Cys(10) with serine resulted in a decreased protein half-life, without significantly altering kinetic properties. Despite the fact that Cys(10) on 17 β -HSD1 seems to have limited potential as a target for new enzyme inhibitors, the present study provides new insight into the structure-function relationships of this enzyme

New Integrable Multi-Component NLS Type Equations on Symmetric Spaces: Z_4 and Z_6 Reductions

The reductions of the multi-component nonlinear Schrodinger (MNLS) type models related to C.I and D.III type symmetric spaces are studied. We pay special attention to the MNLS related to the sp(4), so(10) and so(12) Lie algebras. The MNLS related to sp(4) is a three-component MNLS which finds applications to Bose-Einstein condensates. The MNLS related to so(12) and so(10) Lie algebras after convenient Z_6 or Z_4 reductions reduce to three and four-component MNLS showing new types of chi ^(3)-interactions that are integrable. We briefly explain how these new types of MNLS can be integrated by the inverse scattering method. The spectral properties of the Lax operators L and the corresponding recursion operator Lambda are outlined. Applications to spinor model of Bose-Einstein condensates are discussed.Comment: Reported to the Seventh International conference "Geometry, Integrability and Quantization", June 2--10, 2005, Varna, Bulgari

Fordy-Kulish models and spinor Bose-Einstein condensates

A three-component nonlinear Schrodinger-type model which describes spinor Bose-Einstein condensate (BEC) is considered. This model is integrable by the inverse scattering method and using Zakharov-Shabat dressing method we obtain three types of soliton solutions. The multi-component nonlinear Schrodinger type models related to symmetric spaces C.I Sp(4)/U(2) is studied.Comment: 8 pages, LaTeX, jnmp styl

THORACIC DUCT DRAINAGE WITH AN ACUTE PERITONITIS

No abstrac

Intervention Strategies Promoting Academic Self-Efficacy in Prospective First-Generation College Students: A Literature Review

This literature review first identifies the challenges facing prospective first-generation college students (PFGCS) including a lack of academic preparation in high school, financial barriers created by lower socioeconomic status (SES), and a lack of family support due to unfamiliarity with higher education (Majer, 2009; Olive, 2008; Weiser & Riggio, 2010). Second, this literature review examines the positive correlation between increased academic self-efficacy (ASE) and academic achievement (Elias & Loomis, 2002; Robbins et al., 2004; Zajacova, Lynch, & Espenshade, 2005). Third, this literature review provides a conceptual framework for PFGCS intervention program development based on four strategies found to influence ASE: enactive experiences, vicarious experiences, verbal persuasion, and physiological and affective states (Gandara & Bail, 2001; Habel, 2009; Robbins et al., 2004; Zimmerman, 2000). Fourth, the literature review provides implications including the proposed use of an ASE framework for existing intervention program assessment, a recommendation for the use of an ASE framework to guide high school educator and program administrator activities, and the proposed use of an ASE framework for school counselor planning activities serving the PFGCS population

When Neuroscience Meets Pharmacology: A Neuropharmacology Literature Analysis

Background: Considering the enormous progress in the field of neuropharmacology and its global importance, as well as the lack of bibliometric studies examining this field as a whole, it is a high time to assess the prevailing topics and citation performances of its research works.Methods: Web of Science (WoS) was searched to identify relevant neuropharmacology articles, which were analyzed with reference to (1) publication year, (2) journal title, (3) total citation count, (4) authorship, (5) WoS category, and (6) manuscript type. The identified manuscripts were analyzed with VOSviewer for further bibliometric parameters, such as citation analysis of institutions, countries/regions, and journals, and to visualize the citation patterns of the terms appearing in the titles and abstracts.Results: The literature search resulted in 43,354 manuscripts. Nearly 98% of them were published since the 1990s. The majority of the manuscripts were original articles (n = 31,360) and reviews (n = 11,266). The top five WoS categories associated with the analyzed manuscripts were Pharmacology/Pharmacy (n = 14,892, 34.3%), Neurosciences (n = 11,747, 27.1%), Clinical Neurology (n = 4,981, 11.5%), Psychiatry (n = 4,464, 10.3%), and Biochemistry/Molecular Biology (n = 4,337, 10.0%). Seven of the top ten most prolific institutions were located in the USA, and one each in Canada, Italy, and the UK, respectively. Manuscripts mentioning certain molecules or pharmaceuticals had high citations per manuscript, such as those reporting about anandamide, tetrahydrocannabinol (THC), L-glutamate, clozapine, and curcumin. These terms with at least 50 citations per manuscript were mostly related to cannabis and anti-psychotic drugs, with some dealing with anti-epilepsy effects and Alzheimer's disease.Conclusion: We have identified and analyzed all neuropharmacology articles published since the 1990s. Importantly, the area of neuropharmacology research has been growing steadily due to the global trend in population aging and associated with this continuously increasing number of patients with neuropsychiatric disorders worldwide. It is hoped that identification of new pharmaceutically useful molecules or new clinical applications will continue in the future, in order to improve clinical outcomes and to further strengthen the field of neuropharmacology, a research area cross-linking basic and clinical sciences

Effect of an electric field on a floating lipid bilayer: a neutron reflectivity study

We present here a neutron reflectivity study of the influence of an alternative electric field on a supported phospholipid double bilayer. We report for the first time a reproducible increase of the fluctuation amplitude leading to the complete unbinding of the floating bilayer. Results are in good agreement with a semi-quantitative interpretation in terms of negative electrostatic surface tension.Comment: 12 pages, 7 figures, 1 table accepted for publication in European Physical Journal E Replaced with with correct bibliograph

Monoamine Oxidases (MAOs) as Privileged Molecular Targets in Neuroscience: Research Literature Analysis

Background: Monoamine oxidases (MAOs) were discovered nearly a century ago. This article aims to analyze the research literature landscape associated with MAOs as privileged class of neuronal enzymes (neuroenzymes) with key functions in the processes of neurodegeneration, serving as important biological targets in neuroscience. With the accumulating publications on this topic, we aimed to evaluate the publication and citation performance of the contributors, reveal the popular research themes, and identify its historical roots.Methods: The electronic database of Web of Science (WoS) Core Collection was searched to identify publications related to MAOs, which were analyzed according to their publication year, authorship, institutions, countries/regions, journal title, WoS category, total citation count, and publication type. VOSviewer was utilized to visualize the citation patterns of the words appearing in the titles and abstracts, and author keywords. CRExplorer was utilized to identify seminal references cited by the MAO publications.Results: The literature analysis was based on 19,854 publications. Most of them were original articles (n = 15,148, 76.3%) and reviews (n = 2,039, 10.3%). The top five WoS categories of the analyzed MAO publications were Pharmacology/Pharmacy (n = 4,664, 23.5%), Neurosciences (n = 4,416, 22.2%), Psychiatry (n = 2,906, 14.6%), Biochemistry/Molecular Biology (n = 2,691, 13.6%), and Clinical Neurology (n = 1,754, 8.8%). The top 10 institutions are scattered in the United States, UK, France, Sweden, Canada, Israel, and Russia, while the top 10 countries/regions with the most intensive research on the field of MAOs are the United States, followed by European and Asian countries. More highly cited publications generally involved neurotransmitters, such as dopamine (DA), serotonin, and norepinephrine (NE), as well as the MAO-A inhibitors moclobemide and clorgyline, and the irreversible MAO-B inhibitors selegiline and rasagiline.Conclusion: Through decades of research, the literature has accumulated many publications investigating the therapeutic effects of MAO inhibitors (MAOIs) on various neurological conditions, such as Alzheimer’s disease (AD), Parkinson’s disease (PD), and depression. We envision that MAO literature will continue to grow steadily, with more new therapeutic candidates being tested for better management of neurological conditions, in particular, with the development of multi-target acting drugs against neurodegenerative diseases