bluuebunny/crossref_metadata_2025_split huggingface dataset:
Association and linkage analysis of candidate genes GRP, GRPR, CRHR1, and TACR1 in panic disorder
Authors: Hodges Laura M. , Weissman Myrna M. , Haghighi Fatemeh , Costa Ramiro , Bravo Oscar , Evgrafov Oleg , Knowles James A. , Fyer Abby J. , Hamilton Steven P. 
Published: May 2008

AbstractPanic disorder (PD) is a debilitating anxiety disorder, characterized by recurrent episodes of intense fear that are accompanied by autonomic and psychological symptoms leading to behavioral impairment. Basic research implicates neuropeptide‐signaling genes in the modulation of anxiety and stress. The genes encoding corticotropin releasing hormone receptor 1 (CRHR1), tachykinin receptor 1 (TACR1), gastrin releasing peptide (GRP), and gastrin releasing peptide receptor (GRPR) were selected as candidates for PD based on their biology. Linkage and association analysis in 120 multiplex U.S. PD pedigrees was performed using 21 single nucleotide polymorphisms (SNPs). Parametric and non‐parametric linkage tests in pedigrees, for single point and multipoint analysis, revealed limited support for genetic linkage to TACR1 (parametric and non‐parametric lod scores ∼1). The family‐based association test (FBAT) generated nominal support for allelic association in TACR1 (P = 0.02), and GRP (P = 0.02), findings which must be considered in the light of multiple comparisons. Further exploration of the GRP and TACR1 findings in large case‐control PD samples may provide more definitive evidence implicating these loci in the genetic etiology of PD. © 2008 Wiley‐Liss, Inc.
Analysis of five single nucleotide polymorphisms in the ESR1 gene in cryptorchidism
Authors: Wang Yanping , Barthold Julia , Figueroa Ernesto , González Ricardo , Noh Paul H. , Wang Miao , Manson Jeanne 
Published: May 2008

AbstractBACKGROUNDRecent findings suggest that a specific haplotype, including five single nucleotide polymorphisms (SNPs) in the 3′‐terminal region of the estrogen receptor α gene (ESR1), is associated with the risk for cryptorchidism, but results have been conflicting in different populations. The goal of this study was to further define the association between this specific ESR1 haplotype and the risk for nonsyndromic cryptorchidism in a multiracial American population including Caucasian, African American, and Asian American subjects.METHODSApplied Biosystems TaqMan SNP Genotyping Assays were used to identify the genotypes of the five SNPs in ESR1 in 152 nonsyndromic cryptorchidism cases and 160 healthy controls.RESULTSFor the five SNPs, there were no significant differences in genotype frequencies between cases and controls. The four estimated haplotypes at the 3′ region of ESR1 gene were also not associated with the occurrence of cryptorchidism, but the haplotype AGATC was associated with the severity of cryptorchidism. SNP12 (rs6932902) in ESR1 was not associated with cryptorchidism per se, but was associated with increasing severity of cryptorchidism. Severe cases were more likely to have GG genotype (93%) than moderate (54%) cases (p = .04), and this association was in recessive mode (p = .02). The allele distribution of this SNP was also significantly different between moderate and severe cases: 97% of severe cases had the G allele while only 76% of moderate cases had the G allele (p = .03).CONCLUSIONSSNP12 in ESR1 is not associated with the occurrence of cryptorchidism but is associated with the severity of cryptorchidism. Birth Defects Research (Part A), 2008. © 2008 Wiley‐Liss, Inc.
Refinement of 2q and 7p loci in a large multiplex NTD family
Authors: Stamm Demetra S. , Siegel Deborah G. , Mehltretter Lorraine , Connelly Jessica J. , Trott Alison , Ellis Nathen , Zismann Victoria , Stephan Dietrich A. , George Timothy M. , Vekemans Michel , Ashley‐Koch Allison , Gilbert John R. , Gregory Simon G. , Speer Marcy C. ,   NTD Collaborative Group
Published: May 2008

AbstractBACKGROUND: NTDs are considered complex disorders that arise from an interaction between genetic and environmental factors. NTD family 8776 is a large multigenerational Caucasian family that provides a unique resource for the genetic analysis of NTDs. Previous linkage analysis using a genome‐wide SNP screen in family 8776 with multipoint nonparametric mapping methods identified maximum LOD* scores of ∼3.0 mapping to 2q33.1–q35 and 7p21.1–pter. METHODS: We ascertained an additional nuclear branch of 8776 and conducted additional linkage analysis, fine mapping, and haplotyping. Expression data from lymphoblast cell lines were used to prioritize candidate genes within the minimum candidate intervals. Genomic copy number changes were evaluated using BAC tiling arrays and subtelomeric fluorescent in situ hybridization probes. RESULTS: Increased evidence for linkage was observed with LOD* scores of ∼3.3 for both regions. Haplotype analyses narrowed the minimum candidate intervals to a 20.3 Mb region in 2q33.1–q35 between markers rs1050347 and D2S434, and an 8.3 Mb region in 7p21.1–21.3 between a novel marker 7M0547 and rs28177. Within these candidate regions, 16 genes were screened for mutations; however, no obvious causative NTD mutation was identified. Evaluation of chromosomal aberrations using comparative genomic hybridization arrays, subtelomeric fluorescent in situ hybridization, and copy number variant detection techniques within the 2q and 7p regions did not detect any chromosomal abnormalities. CONCLUSIONS: This large NTD family has identified two genomic regions that may harbor NTD susceptibility genes. Ascertainment of another branch of family 8776 and additional fine mapping permitted a 9.1 Mb reduction of the NTD candidate interval on chromosome 7 and 37.3 Mb on chromosome 2 from previously published data. Identification of one or more NTD susceptibility genes in this family could provide insight into genes that may affect other NTD families. Birth Defects Research (Part A), 2008. © 2008 Wiley‐Liss, Inc.
Effect of low frequency modulated microwave exposure on human EEG: Individual sensitivity
Authors: Hinrikus Hiie , Bachmann Maie , Lass Jaanus , Karai Deniss , Tuulik Viiu 
Published: May 2008

AbstractThe aim of this study was to evaluate the effect of modulated microwave exposure on human EEG of individual subjects. The experiments were carried out on four different groups of healthy volunteers. The 450 MHz microwave radiation modulated at 7 Hz (first group, 19 subjects), 14 and 21 Hz (second group, 13 subjects), 40 and 70 Hz (third group, 15 subjects), 217 and 1000 Hz (fourth group, 19 subjects) frequencies was applied. The field power density at the scalp was 0.16 mW/cm2. The calculated spatial peak SAR averaged over 1 g was 0.303 W/kg. Ten cycles of the exposure (1 min off and 1 min on) at fixed modulation frequencies were applied. All subjects completed the experimental protocols with exposure and sham. The exposed and sham‐exposed subjects were randomly assigned. A computer also randomly assigned the succession of modulation frequencies. Our results showed that microwave exposure increased the EEG energy. Relative changes in the EEG beta1 power in P3‐P4 channels were selected for evaluation of individual sensitivity. The rate of subjects significantly affected is similar in all groups except for the 1000 Hz group: in first group 3 subjects (16%) at 7 Hz modulation; in second group 4 subjects (31%) at 14 Hz modulation and 3 subjects (23%) at 21 Hz modulation; in third group 3 subjects (20%) at 40 Hz and 2 subjects (13%) at 70 Hz modulation; in fourth group 3 subjects (16%) at 217 Hz and 0 subjects at 1000 Hz modulation frequency. Bioelectromagnetics 29:527–538, 2008. © 2008 Wiley‐Liss, Inc.
Development of a benzene vapour sensor utilizing chemiluminescence on Y2O3
Authors: Rao Zhiming , Liu Linjie , Xie Jingyi , Zeng Yuyun 
Published: May 2008

AbstractChemiluminescence (CL) was observed when benzene vapour passed through the surface of Y2O3, TiO2, Y2O3–V2O5, TiO2–Y2O3, Y2O3–Cr2O3, Y2O3–Al2O3 and TiO2–Al2O3, with air as the carrier gas. The strongest CL intensity was found with Y2O3 as the catalyst. A novel benzene sensor based on this kind of CL was developed. Quantitative analysis was performed at the wavelength of 425 nm. Under optimal conditions, CL intensity was directly proportional to the concentration of benzene vapour. The linear range was 4–7018 mg/m3 (r = 0.9981, n = 11), with a detection limit of 1 mg/m3 (the signal:noise ratio was 3). This gas sensor can work continuously for >80 h and has been successfully applied to the real‐time determination of benzene vapour. Copyright © 2008 John Wiley & Sons, Ltd.
Neural correlates of verbal episodic memory in patients with MCI and Alzheimer's disease––a VBM study
Authors: Leube Dirk T. , Weis Susanne , Freymann Kathrin , Erb Michael , Jessen Frank , Heun Reinhard , Grodd Wolfgang , Kircher Tilo T. 
Published: May 2008

AbstractObjectiveThe hippocampus is a key area for episodic memory processes. Hippocampal atrophy is a hallmark feature of Alzheimer's disease (AD). We used a new and automatized morphometric technique to better characterize brain atrophy in subjects with different levels of cognitive deficit.MethodsIn this study 21 participants with Mild Cognitive Impairment (MCI), 12 patients with early AD and 29 elderly control subjects were subjected to high resolution MRI and a neuropsychological test battery. Brain volume across participants, measured by voxel‐based morphometry (VBM), was correlated with verbal memory capacity, measured with a verbal memory test (VLMT).ResultsAtrophy in the anterior hippocampus, the ento‐ and perirhinal cortex as well as the parahippocampal gyrus, middle temporal gyrus and anterior cingulate cortex correlated closely with episodic memory performance.ConclusionsThese brain areas are known to subserve episodic encoding of verbal material. The data contribute to a better understanding of atrophic brain processes in subjects at risk for AD. A combination of neuropsychological testing and voxel‐based morphometry may serve as a diagnostic tool in the future. Copyright © 2008 John Wiley & Sons, Ltd.
HMGA2 gene is a promising target for ovarian cancer silencing therapy
Authors: Malek Anastasia , Bakhidze Elena , Noske Aurelia , Sers Christine , Aigner Achim , Schäfer Reinhold , Tchernitsa Oleg 
Published: May 2008

AbstractOvarian cancer is one of the most lethal gynecological malignancies and the small success rate of routine therapeutic methods justifies efforts to develop new approaches. Evaluation of targets for effective inhibition of ovarian cancer cell growth should precipitate clinical application of gene silencing therapy. In our previous work, we showed upregulation of HMGA2 gene expression as a result of Ras‐induced rat ovarian surface epithelial cell transformation. This gene codes the HMGA2 protein, a member of the high‐mobility group AT‐hook (HMGA) family of nonhistone chromatin proteins. Genome‐wide studies revealed upregulation of the HMGA2 gene in human ovarian carcinomas. Herein we have evaluated over‐expression of the HMGA2 gene, relevant to ovarian cancer, in subsets of human specimens and cell lines by in situ RNA hybridization and RT‐PCR. Transient silencing of HMGA2 gene by means of siRNA inhibited proliferation of those ovarian cancer cells, which over‐express this gene initially. Growth suppression was mediated by cell‐cycle arrest. Stable silencing of highly expressed HMGA2 gene by shRNAi in A27/80, Ovcar‐3 and OAW‐42 ovarian cancer cell lines resulted in growth inhibition because of G1 arrest and increase of apoptosis as well. The tumor growth inhibition effect of HMGA2 silencing for Ovcar‐3 cells was validated in vivo. Our findings revealed that the HMGA2 gene represents a promising target for gene silencing therapy in ovarian cancer. © 2008 Wiley‐Liss, Inc.
Investigating Black‐White differences in prostate cancer prognosis: A systematic review and meta‐analysis
Authors: Evans Simon , Metcalfe Chris , Ibrahim Fowzia , Persad Raj , Ben‐Shlomo Yoav 
Published: May 2008

AbstractThe case‐fatality rate following a diagnosis of prostate cancer is higher for Black men compared to White men. How this elevated rate arises is uncertain, with differences in disease biology, presentation, treatment and comorbidity having been suggested. A systematic search was conducted for articles that reported ethnic differences in overall‐survival, prostate cancer specific survival (PSS) or biochemical recurrence. 48 articles met the inclusion criteria. Black men had worse overall survival (risk ratio 1.35, 95% CI 1.23–1.48) but this was not due to comorbidity alone as PSS and risk of biochemical recurrence were also elevated (1.29, 95% CI 1.13–1.47 and 1.34, 95% CI 1.23–1.46, respectively). Studies adjusting for clinical predictors and socioeconomic variables no longer supported a difference in overall survival (1.01, 95% CI 0.88–1.16), but continued to find an increased risk amongst Black men for PSS (1.13, 95% CI 1.00–1.27) and biochemical recurrence (1.25, 95% CI 1.11–1.41). Similar results were seen for studies from the pre‐PSA era and free‐health care settings. In contrast to others, studies of metastatic cancer did not find evidence of Black‐White differences (p for interaction = 0.01). In conclusion, Black men had a poorer prognosis which was not fully explained by comorbidity, PSA screening, or access to free health care, although few studies measure these factors well. Either management differences for local disease and/or biological differences may be behind Black‐White differences in prostate cancer prognosis. © 2008 Wiley‐Liss, Inc.
Potentiation of chemotherapeutic drugs by energy metabolism inhibitors 2‐deoxyglucose and etomoxir
Authors: Hernlund Emma , Ihrlund Linda Strandberg , Khan Omar , Ates Yildiz Ozlem , Linder Stig , Panaretakis Theocharis , Shoshan Maria C. 
Published: May 2008

AbstractInhibition of energy production as a strategy for potentiation of anticancer chemotherapy was investigated using 1 glycolysis inhibitor and 1 fatty acid β‐oxidation inhibitor—2‐deoxyglucose and etomoxir, respectively, both known to be clinically well tolerated. Eighteen anticancer drugs were screened for potentiation by these inhibitors. 2‐deoxyglucose potentiated acute apoptosis (24 hr) induced mainly by some, but not all, genotoxic drugs, whereas etomoxir had effect only on cisplatin. By contrast, etomoxir did potentiate the overall, 48 hr effects of some genotoxic drugs, and was in addition more efficient than deoxyglucose in potentiating the overall effects of several non‐genotoxic drugs. Both types of potentiation were largely lost in the absence of p53. Because cisplatin was potentiated by both energy inhibitors in both types of assay, it was investigated at additional concentrations and over longer time. Both energy inhibitors strongly potentiated non‐apoptotic concentrations of cisplatin in p53‐wildtype as well as in p53‐deficient, cisplatin‐resistant HCT116 colon carcinoma cells. Reduced ATP levels correlated with, but were not sole determinants, the antiproliferative effects. We conclude that the long‐term effects of cisplatin potentiation are important and either p53‐independent or improved by a lack of p53. We also conclude that although the potentiated drugs as yet have no obvious mechanistic factor in common, the strategy holds promise with genotoxic as well non‐genotoxic anticancer drugs. © 2008 Wiley‐Liss, Inc.
Involvement of endoplasmic reticulum in paclitaxel‐induced apoptosis
Authors: Liao Pei‐Chun , Tan Sai‐Koong , Lieu Chien‐Hui , Jung Hsuan‐Kuang 
Published: May 2008

AbstractThe participation of the mitochondrial pathway in paclitaxel‐induced apoptosis has been well documented. After addition of paclitaxel to U937 cells, however, we observed an early expression of five endoplasmic reticulum (ER) stress response genes that preceded the release of cytochrome c from the mitochondria and the cleavage of the caspases. Involvement of the ER was supported by the following evidence. Paclitaxel treatment not only activated calpain and caspase‐4, but also induced a gradual increase in the cytosolic Ca2+ concentration at 3–6 h. Paclitaxel‐induced apoptosis can be inhibited by the calpain inhibitor calpeptin and IP3 receptor inhibitors. Either buffering of the cytosolic Ca2+ or inhibition of mitochondrial calcium uptake reduced BiP expression. These inhibitors also reduced mitochondrial apoptotic signals, such as mitochondrion membrane potential disruption, cytochrome c release and eventually reduced the death of U937 cells. Paclitaxel‐induced Bax/Bak translocation to the ER and Bax dimerization on the ER membrane occurred within 3 h, which led to a Ca2+ efflux into cytosol. Moreover, we found that cytochrome c translocated to the ER after releasing from mitochondria and then interacted with the IP3 receptor at 12–15 h. This phenomenon has been known to amplify apoptotic signaling. Taken together, ER would seem to contribute to paclitaxel‐induced apoptosis via both the early release of Ca2+ and the late amplification of mitochondria‐mediated apoptotic signals. J. Cell. Biochem. 104: 1509–1523, 2008. © 2008 Wiley‐Liss, Inc.
Increased intracellular [dATP] enhances cardiac contraction in embryonic chick cardiomyocytes
Authors: Schoffstall Brenda , Chase P. Bryant 
Published: May 2008

AbstractAlthough ATP is the physiological substrate for cardiac contraction, cardiac contractility is significantly enhanced in vitro when only 10% of ATP substrate is replaced with 2′‐deoxy‐ATP (dATP). To determine the functional effects of increased intracellular [dATP] ([dATP]i) within living cardiac cells, we used hypertonic loading with varying exogenous dATP/ATP ratios, but constant total nucleotide concentration, to elevate [dATP]i in contractile monolayers of embryonic chick cardiomyocytes. The increase in [dATP]i was estimated from dilution of dye added in parallel with dATP. Cell viability, average contractile amplitude, rates of contraction/relaxation, spontaneous beat frequency, and Ca2+ transient amplitude and kinetics were examined. At total [dATP]i above ∼70 µM, spontaneous contractions ceased, and above ∼100 µM [dATP]i, membrane blebbing was also observed, consistent with apoptosis. Interestingly, [dATP]i of ∼60 µM (∼40% increase over basal [dATP]i levels) enhanced both amplitude of contraction and the rates of contraction and relaxation without affecting beat frequency. With total [dATP]i of ∼60 µM or less, we found no significant change in Ca2+ transients. These data indicate that there is an “optimal” concentration of exogenously loaded [dATP]i that under controlled conditions can enhance contractility in living cardiomyocytes without affecting beat frequency or Ca2+ transients. J. Cell. Biochem. 104: 2217–2227, 2008. © 2008 Wiley‐Liss, Inc.
Differential expression of the two distinct replication protein A subunits from Cryptosporidium parvum
Authors: Rider Stanley Dean , Zhu Guan 
Published: May 2008

AbstractApicomplexan parasites differ from their host by possessing at least two distinct types (long and short) of replication protein A large subunits (RPA1). Different roles for the long and short types of RPA1 proteins have been implied in early biochemical studies, but certain details remained to be elucidated. In the present study, we have found that the Cryptosporidium parvum short‐type RPA1 (CpRPA1A) was highly expressed at S‐phase in parasites during the early stage of merogony (a cell multiplication process unique to this group of parasites), but otherwise present in the cytosol at a much lower level in other cell‐cycle stages. This observation indicates that CpRPA1A is probably responsible for the general DNA replication of the parasite. On the other hand, the long‐type CpRPA1B protein was present in a much lower level in the early life cycle stages, but elevated at later stages involved in sexual development, indicating that CpRPA1B may play a role in DNA recombination. Additionally, CpRPA1B could be up‐regulated by UV exposure, indicating that this long‐type RPA1 is probably involved in DNA repair. Collectively, our data implies that the two RPA1 proteins in C. parvum are performing different roles during DNA replication, repair and recombination in this parasite. J. Cell. Biochem. 104: 2207–2216, 2008. © 2008 Wiley‐Liss, Inc.
Desirability‐based multiobjective optimization for global QSAR studies: Application to the design of novel NSAIDs with improved analgesic, antiinflammatory, and ulcerogenic profiles
Authors: Cruz‐Monteagudo Maykel , Borges Fernanda , Cordeiro M. Natália D. S. 
Published: May 2008

AbstractUp to now, very few reports have been published concerning the application of multiobjective optimization (MOOP) techniques to quantitative structure–activity relationship (QSAR) studies. However, none reports the optimization of objectives related directly to the desired pharmaceutical profile of the drug. In this work, for the first time, it is proposed a MOOP method based on Derringer's desirability function that allows conducting global QSAR studies considering simultaneously the pharmacological, pharmacokinetic and toxicological profile of a set of molecule candidates. The usefulness of the method is demonstrated by applying it to the simultaneous optimization of the analgesic, antiinflammatory, and ulcerogenic properties of a library of fifteen 3‐(3‐methylphenyl)‐2‐substituted amino‐3H‐quinazolin‐4‐one compounds. The levels of the predictor variables producing concurrently the best possible compromise between these properties is found and used to design a set of new optimized drug candidates. Our results also suggest the relevant role of the bulkiness of alkyl substituents on the C‐2 position of the quinazoline ring over the ulcerogenic properties for this family of compounds. Finally, and most importantly, the desirability‐based MOOP method proposed is a valuable tool and shall aid in the future rational design of novel successful drugs. © 2008 Wiley Periodicals, Inc. J Comput Chem, 2008