bluuebunny/crossref_metadata_2025_split huggingface dataset:
NEAP causes down‐regulation of EGFR, subsequently induces the suppression of NGF‐induced differentiation in PC12 cells
Authors: Wang Jiz‐Yuh , Yang Chi‐Hwa , Yeh Chi‐Ling , Lin Chia‐Hua , Chen Yi‐Rong 
Published: October 2008

AbstractNeuroendocrine‐associated phosphatase (NEAP), an atypical dual specificity phosphatase is preferentially expressed in neuroendocrine cells. In this study we found that NEAP, but not NEAP‐(C152S) mutant, evidently reduced epidermal growth factor (EGF) receptor (EGFR) downstream signaling, and impaired cell growth in response to EGF stimulation in PC12 cells. These phenomena were associated with NEAP‐mediated down‐regulation of EGFR mRNA and protein. NEAP had no significant effect on ErbB2/3 expression and phosphorylation levels in response to heregulin, indicating that the negative effect of NEAP on EGFR was selective. We showed that NEAP suppressed EGFR expression via decreasing the EGFR promoter activity and this was mediated through down‐regulations of the Akt pathway and Wilms’ tumor gene product (WT1). Consistent with these results, expression of WT1 reversed the suppressive effect of NEAP on EGFR promoter activity. Additionally, NEAP knockdown by RNA interference enhanced EGFR protein expression and nerve growth factor‐induced differentiation, and an EGFR‐specific inhibitor could reverse the later event. Taken together, our study indicated that NEAP modulates PC12 differentiation via suppression of EGFR expression and signaling.
Notch: from neural development to neurological disorders
Authors: Lathia Justin D. , Mattson Mark P. , Cheng Aiwu 
Published: October 2008

AbstractNotch is an integral membrane protein that functions as receptor for ligands such as jagged and delta that are associated with the surface of neighboring cells. Upon ligand binding, notch is proteolytically cleaved within its transmembrane domain by presenilin‐1 (the enzymatic component of the γ‐secretase complex) resulting in the release of a notch intracellular domain which translocates to the nucleus where it regulates gene expression. Notch signaling plays multiple roles in the development of the CNS including regulating neural stem cell (NSC) proliferation, survival, self‐renewal and differentiation. Notch is also present in post‐mitotic neurons in the adult CNS wherein its activation influences structural and functional plasticity including processes involved in learning and memory. Recent findings suggest that notch signaling in neurons, glia, and NSCs may be involved in pathological changes that occur in disorders such as stroke, Alzheimer’s disease and CNS tumors. Studies of animal models suggest the potential of agents that target notch signaling as therapeutic interventions for several different CNS disorders.
Phosphorylation of tau at Ser214 mediates its interaction with 14‐3‐3 protein: implications for the mechanism of tau aggregation
Authors: Sadik Golam , Tanaka Toshihisa , Kato Kiyoko , Yamamori Hidenaga , Nessa Begum Nurun , Morihara Takashi , Takeda Masatoshi 
Published: October 2008

AbstractThe microtubule associated protein tau is a major component of neurofibrillary tangles in Alzheimer disease brain, however the neuropathological processes behind the formation of neurofibrillary tangles are still unclear. Previously, 14‐3‐3 proteins were reported to bind with tau. 14‐3‐3 Proteins usually bind their targets through specific serine/threonine –phosphorylated motifs. Therefore, the interaction of tau with 14‐3‐3 mediated by phosphorylation was investigated. In this study, we show that the phosphorylation of tau by either protein kinase A (PKA) or protein kinase B (PKB) enhances the binding of tau with 14‐3‐3in vitro. The affinity between tau and 14‐3‐3 is increased 12‐ to 14‐fold by phosphorylation as determined by real time surface plasmon resonance studies. Mutational analyses revealed that Ser214 is critical for the phosphorylation‐mediated interaction of tau with 14‐3‐3. Finally,in vitroaggregation assays demonstrated that phosphorylation by PKA/PKB inhibits the formation of aggregates/filaments of tau induced by 14‐3‐3. As the phosphorylation at Ser214 is up‐regulated in fetal brain, tau’s interaction with 14‐3‐3 may have a significant role in the organization of the microtubule cytoskeleton in development. Also as the phosphorylation at Ser214 is up‐regulated in Alzheimer’s disease brain, tau’s interaction with 14‐3‐3 might be involved in the pathology of this disease.
Activity‐dependent expression of ELAV/Hu RBPs and neuronal mRNAs in seizure and cocaine brain
Authors: Tiruchinapalli Dhanrajan M. , Caron Marc G. , Keene Jack D. 
Published: October 2008

AbstractGrowing evidence indicates that both seizure (glutamate) and cocaine (dopamine) treatment modulate synaptic plasticity within the mesolimbic region of the CNS. Activation of glutamatergic neurons depends on the localized translation of neuronal mRNA products involved in modulating synaptic plasticity. In this study, we demonstrate the dendritic localization of HuR and HuD RNA‐binding proteins (RBPs) and their association with neuronal mRNAs following these two paradigms of seizure and cocaine treatment. Both the ubiquitously expressed HuR and neuronal HuD RBPs were detected in different regions as well as within dendrites of the brain and in dissociated neurons. Quantitative analysis revealed an increase in HuR, HuD and p‐glycogen synthase kinase 3β (GSK3β) protein levels as well as neuronal mRNAs encoding Homer, CaMKIIα, vascular early response gene, GAP‐43, neuritin, and neuroligin protein products following either seizure or cocaine treatment. Inhibition of the Akt/GSK3β signaling pathway by acute or chronic LiCl treatment revealed changes in HuR, HuD, pGSK3β, p‐Akt, and β‐catenin protein levels. In addition, a genetically engineered hyperdopaminergic mouse model (dopamine transporter knockout) revealed decreased expression of HuR protein levels, but no significant change was observed in HuD or fragile‐X mental retardation protein RBPs. Finally, our data suggest that HuR and HuD RBPs potentially interact directly with neuronal mRNAs important for differentiation and synaptic plasticity.
Can Audit Partners Predict Subordinates' Ability to Detect Errors?
Authors: MESSIER, JR. WILLIAM F. , OWHOSO VINCENT , RAKOVSKI CARTER 
Published: October 2008

ABSTRACTThis study examines audit partners' predictions of the ability of managers and seniors to detect financial statement errors. If partners are unable to predict the ability of their subordinates to detect errors, audit effectiveness may be affected. Audit partners are asked to predict which members of the audit team (managers or seniors) are able to detect specific types of errors. These predictions are then compared to errors detected by managers and seniors that are seeded in working papers. The results show that partners (1) exhibit significant overconfidence in the ability of subordinates to detect errors, (2) are more accurate in predicting managers' performance than seniors, (3) are more accurate at predicting subordinates' ability to detect mechanical (simple) errors than conceptual (complex) errors, and (4) are not better at predicting subordinates' ability to detect more frequent and more important errors than less frequent and less important errors.
Disclosure Quality and Management Trading Incentives
Authors: ROGERS JONATHAN L. 
Published: October 2008

ABSTRACTThis study examines whether managers strategically alter disclosure “quality” in response to personal incentives, specifically those derived from trading on their own account. Using changes in market liquidity to proxy for disclosure quality, I find that trading incentives are associated with disclosure quality choices. Tests are performed across three disclosure samples: management forecasts, conference calls, and press releases. Consistent with a desire to reduce the probability of litigation, I find evidence that managers provide higher quality disclosures before selling shares than they provide in the absence of trading. Consistent with a desire to maintain their information advantage, I find some, albeit weaker, evidence that managers provide lower quality disclosures prior to purchasing shares than they provide in the absence of trading.
The 6‐ and 12‐Month Outcomes of Older Medical Inpatients Who Recover from Subsyndromal Delirium
Authors: Cole Martin G. , McCusker Jane , Ciampi Antonio , Belzile Eric 
Published: October 2008

OBJECTIVES: To compare the 6‐ and 12‐month outcomes of patients who recovered from subsyndromal delirium (SSD) by 8 weeks with the outcomes of patients who did not recover or did not have an index episode.DESIGN: Secondary analysis of data collected for a cohort study of the prognosis of delirium.SETTING: University‐affiliated primary acute care hospital.PARTICIPANTS: Older medical inpatients with prevalent, incident, or no SSD were classified into three mutually exclusive groups at 8 weeks (SSD‐recovered, SSD‐not recovered, no SSD) and followed up at 6 and 12 months.MEASUREMENTS: The primary hierarchical composite outcome was death, institutionalization, or cognitive or functional decline at 6 and 12 months. In secondary analyses, components of the primary outcome were examined separately.RESULTS: Of the 129 patients assessed at 8 weeks, 51, 47, and 31 met criteria for SSD‐recovered, SSD‐not recovered and no SSD, respectively. At 6 and 12 months, the primary and secondary outcomes of the SSD‐recovered group were better than the outcomes of the SSD‐not recovered group and, for the most part, intermediate between the outcomes of the SSD‐not recovered and no SSD groups.CONCLUSION: Recovery from SSD appears to predict better longer‐term outcomes than no recovery. Efforts to identify and treat SSD in older medical inpatients may improve outcomes.
Serum concentrations of DKK‐1 decrease in patients with multiple myeloma responding to anti‐myeloma treatment
Authors: Heider Ulrike , Kaiser Martin , Mieth Maren , Lamottke Britta , Rademacher Jessica , Jakob Christian , Braendle Edgar , Stover David , Sezer Orhan 
Published: October 2008

AbstractLytic bone destruction is a hallmark of multiple myeloma (MM) and is because of an uncoupling of bone remodeling. Secretion of Dickkopf (DKK)‐1 by myeloma cells is a major factor which causes inhibition of osteoblast precursors. In this study, the effect of different treatment regimens for MM on serum DKK‐1 was evaluated and correlated with the response to treatment in 101 myeloma patients receiving bortezomib, thalidomide, lenalidomide, adriamycin and dexamethasone (AD) or high‐dose chemotherapy (HDCT) followed by autologous stem cell transplantation (ASCT). At baseline, myeloma patients had increased serum DKK‐1 as compared with patients with MGUS (mean 3786 pg/mL vs. 1993 pg/mL). There was no difference between previously untreated MM patients and patients at relapse. A significant decrease of DKK‐1 after therapy was seen in the following groups: Bortezomib (4059 pg/mL vs. 1862 pg/mL, P = 0.016), lenalidomide (11837 pg/mL vs. 4374 pg/mL, P = 0.039), AD (1668 pg/mL vs. 1241 pg/mL, P = 0.016), and AD + HDCT + ASCT (2446 pg/mL vs. 1082 pg/mL, P = 0.001). Thalidomide led to a non‐significant decrease in DKK‐1 (1705 pg/mL vs. 1269 pg/mL, P = 0.081). Within all groups, a significant decrease of DKK‐1 was only seen in responders (i.e. patients achieving complete remission or partial remission), but not in non‐responders. We show for the first time that serum DKK‐1 levels decrease in myeloma patients responding to treatment, irrespective of the regimen chosen. These data suggest that myeloma cells are the main source of circulating DKK‐1 protein and provide a framework for clinical trials on anti‐DKK‐1 treatment in MM.
Risk factors for infection in haematology patients treated with rituximab
Authors: Kanbayashi Yuko , Nomura Kenichi , Fujimoto Yoshiko , Yamashita Mihoko , Ohshiro Muneo , Okamoto Kousuke , Matsumoto Yosuke , Horiike Shigeo , Takagi Tatsuya , Ishida Yoji , Taniwaki Masafumi ,   Japan Haematology/Oncology Study (J‐HOST) Group (Morioka, Japan)
Published: October 2008

AbstractObjectives:  Although rituximab therapy is not considered to be closely associated with infection, there have been reports of serious infections in patients treated with rituximab. We performed a statistical retrospective analysis to clarify the risk factors for infection in patients receiving rituximab therapy.Methods:  A retrospective study of data from clinical records was performed that targeted haematology patients treated at our university hospital between April 2003 and October 2006. We selected 63 patients with CD20‐positive lymphoma whose peripheral blood immunoglobulin levels had been measured within 6 months before and after rituximab therapy. Logistic regression analysis was used to investigate the risk factors for serious infection in these patients.Results:  The three risk factors identified were: 1) reduction in IgM after administration of rituximab [odds ratio (OR) = 1.032, confidence interval (CI) = 1.007–1.057; P = 0.009], 2) duration of rituximab therapy [OR = 0.962, CI = 0.932–0.994; P = 0.021] and 3) G‐CSF administration [OR = 4.825, CI = 1.411–16.495; P = 0.012].Conclusions:  Rituximab therapy may be associated with infection, indicating the need for sequential monitoring of IgM levels and identification of the optimal interval between rituximab cycles.
B‐cell precursor t(8;14)(q11;q32)‐positive acute lymphoblastic leukemia in children is strongly associated with Down syndrome or with a concomitant Philadelphia chromosome
Authors: Lundin Catarina , Heldrup Jesper , Ahlgren Tomas , Olofsson Tor , Johansson Bertil 
Published: October 2008

AbstractWe review the clinical and cytogenetic features of 44 acute lymphoblastic leukemias (ALLs) with t(8;14)(q11;q32), including three from our department and 41 ascertained in the literature, focusing on age and gender distribution, peripheral blood values, immunophenotypic data, survival and additional chromosomal changes. Most patients are children or young adults, with a median age of 10 yr for children and 28 for adults. There is a male preponderance, particularly in patients with Down syndrome (DS) or in children with concomitant t(9;22)(q34;q11). The median blood values are hemoglobin 72 g/L, platelets 17 × 109/L and white blood cell count 9 × 109/L, with hyperleukocytosis >50 × 109/L having been reported in only ∼10%. All reported cases have had a B‐cell precursor immunophenotype, typically characterized by CD10+, CD19+, CD20+/−, CD22+, CD24+, CD34+, CD45dim/−, CD66c+/− and CD123+. At the time of reporting, 75% of the patients have been alive. The t(8;14) is the sole acquired change in 30%. The most common additional aberrations are t(9;22)(q34;q11), der(14)t(8;14), +21, +X and +14, the presence of which does not seem to confer a prognostic impact. A substantial proportion of the patients have DS (27%) or t(9;22) (16%). All patients with both t(8;14) and t(9;22) have been children without DS; the frequency of t(9;22) in that cohort is 30%. As t(9;22), or its molecular genetic correlate, may escape detection by conventional banding analysis we would strongly suggest that this aberration is actively looked for in pediatric ALL with t(8;14).
Serotonin Transporter Promoter Region (5-HTTLPR) Polymorphism is Associated with the Intravaginal Ejaculation Latency Time in Dutch Men with Lifelong Premature Ejaculation
Authors: Janssen Paddy K.C. , Bakker Steven C. , Réthelyi Janos , Zwinderman Aeilko H. , Touw Daan J. , Olivier Berend , Waldinger Marcel D. 
Published: October 2008

ABSTRACT

Introduction
Lifelong premature ejaculation (LPE) is characterized by persistent intravaginal ejaculation latency times (IELTs) of less than 1 minute, and has been postulated as a neurobiological dysfunction with genetic vulnerability for the short IELTs, related to disturbances of central serotonin (5-hydroxytryptamine [5-HT]) neurotransmission and 5-HT receptor functioning.

Aim
To investigate the relationship between 5-HT transporter gene-linked polymorphism (5-HTTLPR) and short IELTs in men with lifelong PE.

Methods
A prospective study was conducted in 89 Dutch Caucasian men with lifelong PE. IELT during coitus was assessed by stopwatch over a 1-month period. Controls consisted of 92 Dutch Caucasian men. All men with LPE were genotyped for a 5-HTT-promoter polymorphism. Allele frequencies and genotypes of short (S) and long (L) variants of 5-HTTLPR polymorphism were compared between patients and controls. Association between LL, SL, and SS genotypes, and the natural logarithm of the IELT in men with LPE was investigated.

Main Outcome Measures
IELT measured by stopwatch, 5-HTTLPR polymorphism.

Results
In men with lifelong PE, the geometric mean, median, and natural mean IELTs were 21, 26, and 32 seconds, respectively. There were no significant differences in the 5-HTT polymorphism alleles and genotypes between 89 Dutch Caucasian men with LPE (S 47%, L 53%/LL 29%, SL 48%, SS 22%) and 92 Dutch Caucasian controls (S 48%, L 52%/LL 29%, SL 45%, SS 26%). In men with lifelong PE there was a statistically significant difference between LL, SL, and SS genotypes in their geometric mean IELT (P ≤ 0.027); the LL genotypes had significantly shorter IELTs than the SS and SL genotypes.

Conclusions
The 5-HTTLPR polymorphism is associated with significant effects on the latency to ejaculate in men with lifelong PE. Men with SS and SL genotypes have 100% and 90% longer ejaculation time, respectively than men with LL genotypes.
HLA haplotypes in recurrent aphthous stomatitis: a mode­ of inheritance?
Authors: Albanidou‐Farmaki E. , Deligiannidis A. , Markopoulos A. K. , Katsares V. , Farmakis K. , Parapanissiou E. 
Published: October 2008

SummaryThe aim of this study was to investigate the genetic association between recurrent aphthous stomatitis (RAS) and human leucocyte antigen (HLA) class I and II alleles and HLA haplotypes. Families selected had at least one child suffering from recurrent aphthous stomatitis in addition to one or both of the parents. HLA‐A, ‐B and ‐DR alleles were typed in 29 families, 27 nuclear and two extended (121 subjects). HLA haplotypes of all family members with RAS were compared with those who were RAS negative. Although major histocompatibility complex class I and II gene analysis failed to demonstrate any significant association between RAS and HLA antigens, the study of HLA haplotypes revealed a significant association between HLA haplotypes and susceptibility to RAS. The results indicate that susceptibility to RAS segregates in families in association with HLA haplotypes.
DC‐SIGN and DC‐SIGNR polymorphic variants in Northern Asian Indians
Authors: Chaudhary O. , Bhasin R. , Luthra K. 
Published: October 2008

SummaryDendritic cell‐specific intercellular adhesion molecule‐grabbing nonintegrin‐related protein (DC‐SIGNR), along with DC‐SIGN, is suggested to facilitate HIV infection of T cells in trans through binding with HIV gp120. We studied the repeat region polymorphisms in DC‐SIGN and DC‐SIGNR in 100 healthy HIV‐1 seronegative individuals among Northern Asian Indians. Each variant polymorphism obtained by polymerase chain reaction (PCR) was confirmed by cloning and sequencing. Fifty‐four per cent of the healthy seronegative individuals were homozygous for the DC‐SIGNR 7/7 repeat. The heterozygous 7/5 variant was found in 25%, while the 5/5 homozygous genotype was found in 17% of the subjects. Allele 8 was rare and accounted for 4% of the heterozygous genotype (8/7) in the sample population. DC‐SIGN polymorphism was rare, and the genotype 7/7 was most frequent in this study population. Further studies are warranted in a large sample size including high‐risk and seropositive HIV patients to confirm the association of DC‐SIGNR polymorphisms with HIV‐1 susceptibility.
Long‐Term Water Quality and Biological Responses to Multiple Best Management Practices in Rock Creek, Idaho1
Authors: Maret Terry R. , MacCoy Dorene E. , Carlisle Daren M. 
Published: October 2008

Abstract:  Water quality and macroinvertebrate assemblage data from 1981 to 2005 were assessed to evaluate the water quality and biological responses of a western trout stream to the implementation of multiple best management practices (BMPs) on irrigated cropland. Data from Rock Creek near Twin Falls, Idaho, a long‐term monitoring site, were assembled from state and federal sources to provide the evaluation. Seasonal loads of the nonpoint source pollutants suspended sediment (SS), total phosphorus (TP), and nitrate‐nitrite (NN) were estimated using a regression model with time‐series streamflow data and constituent concentrations. Trends in the macroinvertebrate assemblages were evaluated using a number of biological metrics and nonmetric multidimensional scaling ordination. Regression analysis found significant annual decreases in TP and SS flow‐adjusted concentrations during the BMP implementation period from 1983 to 1990 of about 7 and 10%, respectively. These results are coincident with the implementation of multiple BMPs on about 75% of the irrigated cropland in the watershed. Macroinvertebrate assemblages during this time also responded with a change in taxa composition resulting in improved biotic index scores. Taxon specific TP and SS optima, empirically derived from a large national dataset, predicted a decrease in SS concentrations of about 37% (52 to 33 mg/l) and a decrease in TP concentrations of about 50% (0.20 to 0.10 mg/l) from 1981 to 1987. Decreasing trends in TP, SS, and NN pollutant loads were primarily the result of naturally low streamflow conditions during the BMP post‐implementation period from 1993 to 2005. Trends in macroinvertebrate responses during 1993 to 2005 were confounded by the introduction of the New Zealand mudsnail (Potamopyrgus antipodarum), which approached densities of 100,000 per m2 in riffle habitat. The occurrence of this invasive species appears to have caused a major shift in composition and function of the macroinvertebrate assemblages.
Translational Potential of Systems‐Based Models of Inflammation
Authors: Foteinou P.T. , Calvano S.E. , Lowry S.F. , Androulakis I.P. 
Published: October 2008

AbstractA critical goal of translational research is to convert basic science to clinically relevant actions related to disease prevention, diagnosis, and eventually enable physicians to identify and evaluate treatment strategies. Integrated initiatives are identified as valuable in uncovering the mechanism underpinning the progression of human diseases. Tremendous opportunities have emerged in the context of systems biology that aims at the deconvolution of complex phenomena to their constituent elements and the quantification of the dynamic nteractions between these components through the development of appropriate computational and mathematical models. In this review, we discuss the potential role systems‐based translation research can have in the quest to better understand and modulate the nflammatory response.
Flood risk analysis for determining optimal flood protection levels in urban river management
Authors: Morita Masaru 
Published: October 2008

AbstractThe objective of the paper is to present a specific risk‐analysis method for the assessment of optimal flood protection levels in urban flood risk management using intensity–duration–frequency relationships. Risk herein is understood as the product of flood damage potential and its occurrence probability. The risk analysis is based on a geographic information system‐based flood damage prediction model to calculate flood damage for design storms with different return periods. Estimation of the monetary damages for these design storms and their return periods is the prerequisite for quantifying flood risk based on an annual risk density curve. The risk‐analysis method is applied to determine optimal flood protection levels for the Kanda River basin in Tokyo, Japan. It shows how two cost curves can be used: risk cost reduction curves and capital cost curves.