bluuebunny/crossref_metadata_2025_split huggingface dataset:
Use of β-Blockers in Patients with an Implantable Cardioverter Defibrillator
Authors: LaPointe Nancy M Allen , Stafford Judith A , Pappas Paul A , Al-Khatib Sana M , Anstrom Kevin J 
Published: July 2009

Background: Implantable cardioverter defibrillators (ICDs) are indicated for both primary and secondary prevention of sudden cardiac arrest, β-Blockers are also indicated in most patients who have an indication for an ICD; however, their use in this population is not well described. Some clinicians may be unaware of the recommendation for β-blockers in this population. Objective: To explore β-blocker use among ICD recipients. Methods: Adults who received their first ICD at Duke Hospital between July 1999 and July 2004 for primary or secondary prevention of sudden cardiac arrest were identified. Using hospital data, β-blocker use was determined at time of discharge, and characteristics of users were compared with those of nonusers. Continued use of β-blockers after ICD implant was explored in the subset of patients included in the Duke Databank for Cardiovascular Disease (DDCD). Results: The study cohort comprised 804 patients, 652 (81%) with ICD for secondary prevention of sudden cardiac arrest and 152 (19%) for primary prevention. The median age was 65 years and 75% of the patients were men. A total of 544 (68%) received a β-blocker at time of ICD implant. There were no substantial changes in the proportion of patients with β-blocker use from 1999 through 2004, overall or within the primary or secondary prevention groups. However, β-blocker use was higher in the secondary prevention group than in the primary prevention group (69% vs 60%; p = 0.02). A higher proportion of β-blocker users versus nonusers had ischemic heart disease (82% vs 68%; p < 0.0001), heart failure (84% vs 71%; p < 0.0001), previous myocardial infraction (51 % vs 44%; p = 0.05), and ventricular arrhythmias (82% vs 76%; p = 0.04). Of the 425 patients included in the DDCD, only 241 (57%) were receiving β-blockers at time of implant and during clinical follow-up. Conclusions: Lower than optimal use of β-blockers suggests the need for new methods of including evidence-based medications in clinical practice, especially for complex patients for whom numerous clinical practice guidelines may apply.
Grade differences in reading motivation among Hong Kong primary and secondary students
Authors: Lau Kit‐Ling 
Published: July 2009

Background Most previous studies in Western societies have demonstrated a general decline in school motivation. However, it is not clear whether motivational decline occurs uniformly for all students. The moderating effects of individual and cultural differences on students' motivational decline need to be further explored.Aims This study aimed to examine the grade differences in students' reading motivation, including self‐efficacy, intrinsic motivation, extrinsic motivation, and social motivation, in a Chinese educational context. Grade by gender and grade by school‐average achievement interactions were also checked to explore the role of individual differences in students' motivational changes.Sample A total of 1,794 students (860 boys and 934 girls) volunteered to take part in this study, of whom 648 were Grade 4–6 students from 11 primary schools, 627 were Grade 7–9 students from 12 junior secondary schools, and 519 Grade 10–11 students from 6 senior secondary schools.Method A Chinese version of the Motivation for Reading Questionnaire (CRMQ) was administered to all participants during regular class periods by their teachers. Reliability analyses and confirmatory factor analysis (CFA) were first undertaken to assess the psychometric quality of the CRMQ. Then, multisample CFA was conducted to examine whether the factor structure of the CRMQ was equivalent across students at different grade levels. Grade differences in various reading motivation constructs as well as grade × gender and grade × school‐average achievement interactions were examined using multiple‐indicator‐multiple‐causes modelling.Results The findings of this study supported the reliability and the factor structure of the CRMQ in measuring the reading motivation of Chinese students at different grade levels. The factor pattern of the CRMQ was invariant across primary, junior secondary, and senior secondary students in multisample CFA. As far as the scores on the four reading motivation constructs were concerned, students scored most highly on intrinsic motivation, followed by self‐efficacy, extrinsic motivation, and social motivation. Significant grade differences were found in all reading motivation constructs whereas only a few grade by gender and grade by school‐average interactions were found.Conclusion Consistent with previous studies in Western countries, the findings suggest that motivational decline is also a common phenomenon among Chinese students in Hong Kong. In addition, the pattern of motivational differences is generally consistent among students with different genders and from schools with different achievement levels. The implications of these findings for understanding Chinese students' reading motivation and for planning effective reading instruction to enhance their motivation are discussed.
Association between kallikrein-related peptidases (KLKs) and macroscopic indicators of semen analysis: their relation to sperm motility
Authors: Emami Nashmil , Scorilas Andreas , Soosaipillai Antoninus , Earle Tammy , Mullen Brendan , Diamandis Eleftherios P. 
Published: June 2009

AbstractHuman kallikrein-related peptidases (KLKs) are a family of proteases, the majority of which are found in seminal plasma and have been implicated in semen liquefaction. Here, we examined the clinical value of seminal KLKs in the evaluation of semen quality and differential diagnosis and etiology of abnormal liquefaction and/or viscosity. KLK1–3, 5–8, 10, 11, 13, and 14 were analyzed, using highly specific ELISA assays. Samples were categorized into four clinical groups, according to their state of liquefaction and viscosity. Data were compared between the clinical groups and in association with other parameters of sperm quality, including number of motile sperms, straight line speed, sperm concentration, volume, pH, and patient age. Seminal KLKs were found to be differentially expressed in the four clinical groups. Combination of KLK2, 3, 13, and 14 and KLK1, 2, 5, 6, 7, 8, 10, 13, and 14 showed very strong discriminatory potential for semen liquefaction and viscosity, respectively. Liquefaction state was associated with several parameters of sperm motility. Finally, KLK14 was differentially expressed in asthenospermic cases. In conclusion, the expression level of several seminal plasma KLKs correlates with liquefaction and viscosity indicators of semen quality and may aid in their differential diagnosis and etiology.
A dual role of the N-terminal FQQI motif in GLUT4 trafficking
Authors: Bernhardt Ulrike , Carlotti Françoise , Hoeben Rob C. , Joost Hans-Georg , Al-Hasani Hadi 
Published: June 2009

Abstract
In adipocytes, the glucose transporter GLUT4 recycles between intracellular storage vesicles and the plasma membrane. GLUT4 is internalized by a clathrin- and dynamin-dependent mechanism, and sorted into an insulin-sensitive storage compartment. Insulin stimulation leads to GLUT4 accumulation on the cell surface. The N-terminal F5QQI motif in GLUT4 has been shown previously to be required for sorting of the protein in the basal state. Here, we show that the FQQI motif is a binding site for the medium chain adaptin μ1, a subunit of the AP-1 adaptor complex that plays a role in post-Golgi/endosomal trafficking events. In order to investigate the role of AP-1 and AP-2 in GLUT4 trafficking, we generated 3T3-L1 adipocytes expressing HA-GLUT4-GFP and knocked down the AP-1 and AP-2 complex by RNAi, respectively. In AP-1 and AP-2 knockdown adipocytes, GLUT4 accumulates at the cell surface in the basal state, consistent with a role of AP-1 in post-endosomal sorting of GLUT4 to the insulin-sensitive storage compartment, and of AP-2 in clathrin-mediated endocytosis. Our data demonstrate a dual role of the F5QQI motif and support the conclusion that the AP complexes direct GLUT4 trafficking and endocytosis.
Effect of a quaternary pentamine on RNA stabilization and enzymatic methylation
Authors: Hayrapetyan Armine , Grosjean Henri , Helm Mark 
Published: June 2009

Abstract
Extreme thermophiles produce unusually long polyamines, including the linear caldopentamine (Cdp) and the branched pentamine tetrakis(3-aminopropyl)-ammonium (Taa), with the latter containing a central quaternary ammonium moiety. Here we compare the interaction of these two pentamines with RNA by studying the heat denaturation, electrophoretic behavior, and ability of tRNA to be methylated in vitro by purified tRNA methyltransferases under various salt conditions. At concentrations in the micromolar range, branched Taa causes a considerable increase in the melting temperature (T
m) of yeast tRNAPhe transcripts by >20°C, which is significantly greater than stabilization by the linear Cdp. In non-denaturing gel electrophoresis, strong and specific binding to Taa, but not to Cdp, was clearly observed for tRNAPhe. In both types of experiments, polyamines and monovalent metal ions competed for binding sites. Structural probing revealed no significant conformational changes in tRNA on Taa binding. In post-transcriptional in vitro methylation reactions, the formation of m2G/m2
2G by the methyltransferase Trm1p and of m1A by TrmIp were not affected or only slightly stimulated by polyamines. In contrast, Taa specifically inhibited Trm4p-dependent formation of m5C only in tRNAPhe, likely by occupying sites that are relevant to RNA recognition by the methyltransferase.
The effect of endogenous preproneuropeptide Y leucine 7 to proline 7 polymorphism on growth and apoptosis in primary cultured HUVECs
Authors: Kaipio Katja , Kallio Jaana , Pesonen Ullamari 
Published: June 2009

Abstract
Neuropeptide Y (NPY) is a universally expressed neuropeptide involved in the regulation of several physiological functions. The rather common leucine7 to proline7 (L7P) polymorphism in the signal peptide of preproNPY is a functional substitution, which changes the processing and release of NPY in cells. The mutation is associated with altered lipid levels and accelerated atherosclerosis in humans. Based on previous studies, we investigated the effect of the Pro7 allele in endothelial cells, which are known to play a role in the development of atherosclerosis. Cell proliferation and apoptosis were studied in primary cultured, genotyped human umbilical vein endothelial cells (HUVECs). Our results indicate that cells with the [p.L7]+[p.P7] genotype seem to have a tendency to be more sensitive to the growth stimulating effect of NPY and less sensitive to the effect of vascular endothelial growth factor compared to cells with the [p.L7]+[p.L7] genotype. Additionally, cells with the [p.L7]+[p.P7] genotype seem to be more sensitive to apoptosis than [p.L7]+[p.L7] cells. We speculate that the L7P substitution in preproNPY might cause a state of cellular pre-senescence, leading to endothelial dysfunction. This might be one reason for the associations of the L7P polymorphism with atherosclerosis and type II diabetes found in clinical studies.
Peritumoral administration of GPI-anchored TIMP-1 inhibits colon carcinoma growth in Rag-2 γ chain-deficient mice
Authors: Raggi Matthias C. , Djafarzadeh Roghieh , Muenchmeier Niklas , Hofstetter Monika , Jahn Birgit , Rieth Nicole , Nelson Peter J. 
Published: June 2009

Abstract
Exogenous application of recombinant TIMP-1 protein modified by addition of a glycosylphosphatidylinositol (GPI) anchor allows efficient insertion of the fusion protein into cell membranes. This ‘cell surface engineering’ leads to changes in the proteolytic environment. TIMP-1-GPI shows enhanced as well as novel in vitro biological activities including suppression of proliferation, reduced migration, and inhibition of invasion of the colon carcinoma cell line SW480. Treatment of SW480 tumors implanted in Rag (-/-) common γ chain (-/-) C57BL/6 mice with peritumorally applied TIMP-1-GPI, control rhTIMP-1 protein, or vehicle shows that TIMP-1-GPI leads to a significant reduction in tumor growth.
Metzincin's canonical methionine is responsible for the structural integrity of the zinc-binding site
Authors: Oberholzer Anselm E. , Bumann Mario , Hege Thomas , Russo Santina , Baumann Ulrich 
Published: June 2009

Abstract
The metzincins constitute a subclan of metalloproteases possessing a HEXXHXXGXXH/D zinc-binding consensus sequence where the three histidines are zinc ligands and the glutamic acid is the catalytic base. A completely conserved methionine is located downstream of this motif. Families of the metzincin clan comprise, besides others, astacins, adamalysins proteases, matrix metallo-proteases, and serralysins. The latter are extracellular 50 kDa proteases secreted by Gram-negative bacteria via a type I secretion system. While there is a large body of structural and biochemical information available, the function of the conserved methionine has not been convincingly clarified yet. Here, we present the crystal structures of a number of mutants of the serralysin member protease C with the conserved methionine being replaced by Ile, Ala, and His. Together with our former report on the leucine and cysteine mutants, we demonstrate here that replacement of the methionine side chain results in an increasing distortion of the zinc-binding geometry, especially pronounced in the χ2 angles of the first and third histidine of the consensus sequence. This is correlated with an increasing loss of proteolytic activity and a sharp increase of flexibility of large segments of the polypeptide chain.
Mitochondrial tRNA import – the challenge to understand has just begun
Authors: Alfonzo Juan D. , Söll Dieter 
Published: June 2009

Abstract
Mitochondrial translation is important for the synthesis of proteins involved in oxidative phosphorylation, which yields the bulk of the ATP made in cells. During evolution most mitochondria-containing organisms have lost tRNA genes from their mitochondrial genomes. Thus, to support the essential process of nuanced mitochondrial translation, mechanisms to actively transport tRNAs from the cytoplasm across the mitochondrial membranes into the mitochondrion have evolved. Here, we review the currently known tRNA import mechanisms, comment on recent discoveries of various import factors, and suggest a rationale for forces that lie behind the evolution of mitochondrial tRNA import.
Induced human pluripotent stem cells: promises and open questions
Authors: Rolletschek Alexandra , Wobus Anna M. 
Published: June 2009

Abstract
Adult cells have been reprogrammed into induced pluripotent stem (iPS) cells by introducing pluripotency-associated transcription factors. Here, we discuss recent advances and challenges of in vitro reprogramming and future prospects of iPS cells for their use in diagnosis and cell therapy. The generation of patient-specific iPS cells for clinical application requires alternative strategies, because genome-integrating viral vectors may cause insertional mutagenesis. Moreover, when suitable iPS cell lines will be available, efficient and selective differentiation protocols are needed to generate transplantable grafts. Finally, we point to the requirement of a regulatory framework necessary for the commercial use of iPS cells.
Epidermal growth factor receptor signaling in liver cell proliferation and apoptosis
Authors: Reinehr Roland , Häussinger Dieter 
Published: June 2009

Abstract
Recent evidence suggests that epidermal growth factor receptor (EGFR)-dependent signaling contributes to liver cell proliferation, as well as to apoptotic liver cell death, and represents an important regulator of hepatic regeneration. This article summarizes recent findings on the molecular mechanisms involved in EGFR-mediated cell proliferation and apoptosis. The emphasis is on the interplay between EGFR and CD95 (Fas, APO-1) death receptor-signaling, which is determined by the signaling context and liver cell type investigated.
Effect of curcumin on amyloidogenic property of molten globule-like intermediate state of 2,5-diketo-d-gluconate reductase A
Authors: Sarkar Nandini , Narain Singh Abhay , Kumar Dubey Vikash 
Published: June 2009

Abstract
We identified a molten globule-like intermediate of 2,5-diketo-d-gluconate reductase A (DKGR) at pH 2.5, which has a prominent β-sheet structure. The molten globule state of the protein shows amyloidogenic property >50 μm protein concentration. Interestingly, a 1:1 molar ratio of curcumin prevents amyloid formation as shown by the Thioflavin-T assay and atomic force microscopy. To the best of our knowledge, this is the first report on amyloid formation by an (α/β)8-barrel protein. The results presented here indicate that the molten globule state has an important role in amyloid formation and potential application of curcumin in protein biotechnology as well as therapeutics against amyloid diseases.
Influence of prematurity and growth restriction on the adipokine profile, IGF1, and ghrelin levels in cord blood: relationship with glucose metabolism
Authors: Martos-Moreno Gabriel Á , Barrios Vicente , Sáenz de Pipaón Miguel , Pozo Jesús , Dorronsoro Izaskun , Martínez-Biarge Miriam , Quero José , Argente Jesús 
Published: June 2009

ObjectiveTo determine the influence of gestational age and fetal growth restriction on the cord blood adipokine profile, IGF1, and ghrelin levels, and their relationship with glucose metabolism.Study designOne hundred and ninety newborns (99 preterm and 91 full term) were studied and, according to their anthropometry at birth, classified as small (SGA) or adequate for gestational age (AGA).MethodsVenous cord blood serum levels of IGF1, IGF binding protein 3 (IGFBP-3), adiponectin, resistin, leptin, soluble leptin receptor (sOB-R), tumoral necrosis factor-α, interleukin 6 (IL-6), total ghrelin, and acylated ghrelin were determined and compared between preterm and full-term, as well as between SGA and AGA, newborns. Correlations with newborn weight, gestational age, and homeostatic model assessment (HOMA) index, as an index of insulin resistance, were determined.ResultsPreterm newborns had higher HOMA, sOB-R, resistin, and IL-6 and lower IGF1, IGFBP-3, leptin, and adiponectin levels than full-term newborns. SGA had lower IGF1, IGFBP-3, leptin, IL-6, and adiponectin and higher sOB-R and total ghrelin than AGA newborns. Adiponectin and HOMA showed independent positive and negative correlations with gestational age respectively, but not with neonatal weight. Birth weight was correlated positively with IGF1 and leptin levels and negatively with total ghrelin ones.ConclusionsOur findings suggest that the lack of proper acquisition of adipose tissue by the fetus either due to prematurity or to fetal growth restriction is associated with changes in the cord blood adipokine profile that may contribute to the impairment of glucose metabolism.
Restricted thyroglobulin antibody epitope specificities in subjects with type 1 diabetes mellitus
Authors: Okosieme O E , Wijeyaratne C N , Lazarus J H , Premawardhana L D K E 
Published: June 2009

ObjectivesFollowing iodisation in Sri Lanka we observed a high prevalence of thyroglobulin antibodies (TgAbs) in type 1 diabetic (T1DM) patients. The clinical significance of these TgAbs is uncertain. We sought to obtain a detailed epitope analysis of TgAbs in T1DM patients recruited from diabetes clinics and to compare these with TgAb epitope specificities in patients with autoimmune thyroid disease (AITD) and healthy individuals in that country.Design and methodsWe used a panel of 10 Tg-MAbs in competitive ELISA reactions in a prospective study of subjects recruited from Colombo, to determine the epitopes recognised by TgAb-positive patients with T1DM (n=58, 34F:24M, median age 16 years), AITD patients (n=42, 33F:9M, median age 37 years) and healthy subjects (n=50, 39F:11M, median age 27 years). The outcomes were a comparison of reactivity with six Tg clusters (I–VI) in these subjects, and the relation of epitope specificity patterns with free thyroxine and TSH.ResultsPatients with T1DM and AITD but not healthy control subjects preferentially recognised the immunodominant clusters, I, III and IV. Patients with these narrow epitope specificities had higher median TSH levels (1.60 vs 1.06;P=0.01), and were more frequently positive for antibodies to thyroid peroxidase than those with broad specificities (52.3 vs 7.1%;P=0.004).ConclusionsThe TgAb epitope specificities in euthyroid Sri Lankans with T1DM are similar to AITD patients. TgAb epitope studies may potentially identify T1DM patients at risk of thyroid dysfunction.
Anthracyclines in Early-Stage Breast Cancer: Is It the End of an Era?
Authors: Robson Danny , Verma Sunil 
Published: June 2009

Abstract
Anthracycline regimens have been the mainstay of adjuvant care in breast cancer for &gt;20 years. A growing body of clinical experience has uncovered an unacceptable rate of significant cardiac and leukomogenic toxicities. A systematic review of the literature was performed highlighting anthracycline- and nonanthracycline-based adjuvant regimens. The published data suggest that nonanthracycline alternatives are less toxic than anthracycline-containing regimens and equally, if not more, efficacious. Molecular predictors, such as human epidermal growth factor receptor 2 and topoisomerase II α, are further refining the optimal role of anthracyclines. With these new advances, the current role of anthracycline-based chemotherapy in early-stage breast cancer demands re-examination.
Role of Hematopoietic Stem Cell Transplant in the Management of Follicular Lymphoma
Authors: Foster Matthew , Gabriel Don A. , Shea Thomas 
Published: June 2009

Learning Objectives
Evaluate recent data regarding outcomes of autologous and allogeneic stem cell transplant for follicular lymphoma. Apply patient and disease characteristics to predict favorable post-transplant outcomes for patients with follicular lymphoma. Enumerate the indications for referral of patients with follicular lymphoma to a transplant center. Compare the advantages and disadvantages of allogeneic versus autologous stem cell transplant for follicular lymphoma.
This article is available for continuing medical education credit at CME.TheOncologist.com.