bluuebunny/crossref_metadata_2025_split huggingface dataset:
Phenotypic clustering of yeast mutants based on kinetochore microtubule dynamics
Authors: Jaqaman K. , Dorn J. F. , Marco E. , Sorger P. K. , Danuser G. 
Published: May 2007

Abstract
Motivation: Kinetochores are multiprotein complexes which mediate chromosome attachment to microtubules (MTs) of the mitotic spindle. They regulate MT dynamics during chromosome segregation. Our goal is to identify groups of kinetochore proteins with similar effects on MT dynamics, revealing pathways through which kinetochore proteins transform chemical and mechanical input signals into cues of MT regulation.
Results: We have developed a hierarchical, agglomerative clustering algorithm that groups Saccharomyces cerevisiae strains based on MT-mediated chromosome dynamics measured by high-resolution live cell microscopy. Clustering is based on parameters of autoregressive moving average (ARMA) models of the probed dynamics. We have found that the regulation of wildtype MT dynamics varies with cell cycle and temperature, but not with the chromosome an MT is attached to. By clustering the dynamics of mutants, we discovered that the three genes IPL1, DAM1 and KIP3 co-regulate MT dynamics. Our study establishes the clustering of chromosome and MT dynamics by ARMA descriptors as a sensitive framework for the systematic identification of kinetochore protein subcomplexes and pathways for the regulation of MT dynamics.
Availability: The clustering code, written in Matlab, can be downloaded from http://lccb.scripps.edu. (‘download’ hyperlink at bottom of website).
Contact: kjaqaman@scripps.edu
Supplementary information: Supplementary data are available at Bioinformatics online.
Assessment of survival prediction models based on microarray data
Authors: Schumacher Martin , Binder Harald , Gerds Thomas 
Published: May 2007

AbstractMotivation: In the process of developing risk prediction models, various steps of model building and model selection are involved. If this process is not adequately controlled, overfitting may result in serious overoptimism leading to potentially erroneous conclusions.Methods: For right censored time-to-event data, we estimate the prediction error for assessing the performance of a risk prediction model (Gerds and Schumacher, 2006; Graf et al., 1999). Furthermore, resampling methods are used to detect overfitting and resulting overoptimism and to adjust the estimates of prediction error (Gerds and Schumacher, 2007).Results: We show how and to what extent the methodology can be used in situations characterized by a large number of potential predictor variables where overfitting may be expected to be overwhelming. This is illustrated by estimating the prediction error of some recently proposed techniques for fitting a multivariate Cox regression model applied to the data of a prognostic study in patients with diffuse large-B-cell lymphoma (DLBCL).Availability: Resampling-based estimation of prediction error curves is implemented in an R package called pec available from the authors.Contact: sec@imbi.uni-freiburg.de
Automated Improvement of Domain ANnotations using context analysis of domain arrangements (AIDAN)
Authors: Beaussart Francois , Weiner January , Bornberg-Bauer Erich 
Published: May 2007

AbstractMotivation: Since protein domains are the units of evolution, databases of domain signatures such as ProDom or Pfam enable both a sensitive and selective sequence analysis. However, manually curated databases have a low coverage and automatically generated ones often miss relationships which have not yet been discovered between domains or cannot display similarities between domains which have drifted apart.Methods: We present a tool which makes use of the fact that overall domain arrangements are often conserved. AIDAN (Automated Improvement of Domain ANnotations) identifies potential annotation artifacts and domains which have drifted apart. The underlying database supplements ProDom and is interfaced by a graphical tool allowing the localization of single domain deletions or annotations which have been falsely made by the automated procedure.Availability: http://www.uni-muenster.de/Evolution/ebb/Services/AIDANContact: ebb@uni-muenster.deSupplementary information: Supplementary data are available at Bioinformatics online.
Interaction of Cochlear Nucleus Explants With Semiconductor Materials
Authors: Mlynski Robert , Volkenstein Stefan , Hansen Stefan , Brors Dominik , Ebmeyer Joerg , Dazert Stefan 
Published: May 2007

AbstractObjective/Hypothesis: Implantable hearing devices such as cochlear implants and auditory brainstem implants deliver auditory information through electrical stimulation of auditory neurons. The combination of microelectronic electrodes with auditory nerve cells may lead to further improvement of the hearing quality with these devices. Whereas several kinds of neurons are known to grow on semiconductor substrates, interactions of cochlear nucleus (CN) neurons with such materials have yet to be described.Materials and Methods: To investigate survival and growth behavior of CN neurons on different semiconductor materials. CN explants from postnatal day 10 Sprague‐Dawley rats were cultured for 96 hours in Neurobasal medium on polished and unpolished silicon wafers (p‐type Si {100} and p‐type Si3N4{100}) as well as plastic surface. These surfaces had been coated with poly‐L‐lysine and laminin. Neuronal outgrowth was examined using image analysis software after immunohistologic staining for neurofilament. Neurite length and directional changes were quantified. Additionally, neurite morphology and adhesion to the semiconductor material was evaluated by scanning electron microscopy.Results: Although proper adhesion of CN explants was seen, no neurite growth could be detected on unpolished silicon wafers (Si and Si3N4). Compared with the other test conditions, polished, laminin‐coated Si3N4 wafers showed best biocompatibility regarding neurite length and number per explant. CN explants developed a mean of eight neurons with an average length of 236 μm in 96 hours of culture on these wafers.Conclusion: The results of this study demonstrate the general possibility of CN neuron growth in culture on semiconductors in vitro. The differences in neuron length and number per explant indicate that the growth of CN neurons is influenced by the semiconductor substrate as well as extracellular matrix proteins, with laminin‐coated p‐type Si3N4{100} being a preferable material for future hybrid experiments on auditory‐neuron semiconductor chips.
Gastric and intestinal claudin expression at the invasive front of gastric carcinoma
Authors: Matsuda Yoshiko , Semba Shuho , Ueda Junya , Fuku Takeichi , Hasuo Tadateru , Chiba Hideki , Sawada Norimasa , Kuroda Yoshikazu , Yokozaki Hiroshi 
Published: May 2007

Like gastric and intestinal mucins, the tight junction proteins called claudins can be used to determine the differentiation of gastric mucosa. We investigated the expression of claudins in gastric cancer and proposed a new claudin‐based gastric cancer classification system. The expression of gastric (claudin‐18) and intestinal (claudin‐3 and claudin‐4) claudins in non‐neoplastic gastric mucosa (with intestinal metatplasia [IM], 78 cases; without IM, 88 cases) and 94 gastric cancers was analyzed immunohistochemically, as was the expression of gastric (MUC5A and MUC6) and intestinal (CD10 and MUC2) mucins. Heterogeneous expression of claudin‐3, claudin‐4 and claudin‐18 was detected in advanced gastric cancer; however, there was no significant association between the claudins and the clinicopathological parameters. These gastric cancer tissues were also subclassified into claudin‐based phenotypes: gastric claudin (G‐CLDN), 28 cases (30%); intestinal claudin (I‐CLDN), 41 cases (44%); and unclassified claudin (U‐CLDN), 25 cases (26%). Interestingly, the U‐CLDN gastric cancers had worse malignancy grades, not only in size and invasiveness but also in potential metastatic ability and patient outcome. Although the mucin‐based gastric cancer classification was also assessed, no significant correlation was found between mucin production and clinicopathological parameters. These observations suggest that loss of claudin expression may enhance the grade of malignancy of gastric cancer in vivo. Classification of gastric cancers using gastric and intestinal claudins is a good biomarker for assessing the risk of poor prognosis. (Cancer Sci 2007; 98: 1014–1019)
BCL2L2 is a probable target for novel 14q11.2 amplification detected in a non‐small cell lung cancer cell line
Authors: Kawasaki Tsutomu , Yokoi Sana , Tsuda Hitoshi , Izumi Hiroyuki , Kozaki Ken‐ichi , Aida Shinsuke , Ozeki Yuichi , Yoshizawa Yasuyuki , Imoto Issei , Inazawa Johji 
Published: May 2007

Amplification of chromosomal DNA is thought to be one of the mechanisms that activates cancer‐related genes in tumors. In a previous genome‐wide screening of DNA copy number aberrations in a panel of non‐small cell lung cancer (NSCLC) cell lines using an in‐house bacterial artificial chromosome‐based array, we identified a novel amplification at 14q11.2 in HUT29 cells derived from human lung adenocarcinoma. To identify the most likely target for the 14q11.2 amplification, we determined the extent of the amplicon by fluorescence in situ hybridization and then analyzed NSCLC cell lines for the expression levels of 28 genes present within the 1‐Mb amplified region. Significant overexpression in the HUT29 cell line with amplification, relatively frequent overexpression in additional NSCLC cell lines compared with an immortalized normal lung epithelial cell line, and reported information about the function of each candidate gene prompted us to characterize the BCL2‐like2 (BCL2L2) gene, a prosurvival member of the BCL2 family, as the most likely target for the 14q11.2 amplicon. Immunohistochemical analysis of 61 primary cases of lung adenocarcinoma demonstrated that BCL2L2 overexpression was significantly associated with tumor stage and differentiation status, and tended to be associated with a poorer prognosis. Downregulation of BCL2L2 expression using small interfering RNA dramatically inhibited the growth of HUT29 cells, but showed no effect on anticancer reagent‐induced cell death of the same cell line. These findings demonstrate that overexpressed BCL2L2, through amplification or other mechanisms, promotes the growth of NSCLC, especially the adenocarcinoma subtype, and might be a therapeutic target. (Cancer Sci 2007; 98: 1070–1077)
Robin Coombs: his life and contribution to haematology and transfusion medicine
Authors: Pamphilon Derwood H , Scott Marion L 
Published: May 2007

SummaryRobin Coombs was the last survivor of the distinguished group of immunologists that included Philip Gell, John Humphrey, John Marrack, Peter Medawar and Robert White and who were responsible for the renaissance of British Immunology after the Second World War. He is best remembered for describing the antiglobulin test that bears his name. The antiglobulin test revolutionised the diagnosis of haemolytic diseases and the compatibility testing of blood for transfusion. In all, Coombs authored over 200 scientific papers. Haemagglutination reactions became widely used in the diagnosis of a range of infectious agents. Together with Philip Gell, he devised the classification of allergic reactions; these were published in the textbook ‘Clinical Aspects of Immunology’, which he and Gell first edited in 1963 and which became the leading textbook on medical immunology. Robin Coombs was also one of the founders of the British Society for Immunology.
Impact of imatinib therapy on the use of allogeneic haematopoietic progenitor cell transplantation for the treatment of chronic myeloid leukaemia
Authors: Giralt Sergio A. , Arora Mukta , Goldman John M. , Lee Stephanie J. , Maziarz Richard T. , McCarthy Philip L. , Sobocinski Kathleen A. , Horowitz Mary M. ,   on behalf of the Chronic Leukemia Working Committee of the Center for International Blood and Marrow Transplant Research
Published: May 2007

SummaryThe discovery and approval of imatinib drastically changed the therapeutic algorithm for chronic myeloid leukaemia (CML). Imatinib is now considered the therapy of choice for patients with newly diagnosed CML, including those previously considered candidates for allogeneic haematopoietic cell transplantation (HCT). We compared numbers and types of allogeneic HCTs performed for CML in North America before and after the introduction of imatinib, and publication of the International Randomized Trial of Interferon and STI571 (IRIS) using transplants reported to the Center for International Blood and Marrow Transplant Research (CIBMTR). The number of HCTs for CML registered with the CIBMTR in 1998 was 617; 62% were performed in first chronic phase (CP1). Only 1% of patients had received imatinib prior to transplantation. In 2003, the number of HCTs reported was 223; 44% were performed in CP1 and 77% of patients received imatinib prior to transplantation. The introduction of imatinib therapy has had a profound impact on the use of allogeneic transplantation for CML, with a marked decrease in the number of transplants for CML and an accompanying decrease in the proportion done in CP1. Most patients now receive a trial of imatinib before proceeding to HCT.
G‐CSF is not necessary to maintain over 99% dose–intensity with ABVD in the treatment of Hodgkin lymphoma: low toxicity and excellent outcomes in a 10‐year analysis
Authors: Evens Andrew M. , Cilley Jeffrey , Ortiz Taylor , Gounder Mrinal , Hou Nanjiang , Rademaker Alfred , Miyata Sarah , Catsaros Kara , Augustyniak Connie , Bennett Charles L , Tallman Martin S. , Variakojis Daina , Winter Jane N. , Gordon Leo I. 
Published: May 2007

SummaryDose–intensity of chemotherapy is important in the treatment of Hodgkin lymphoma (HL) and granulocyte‐colony stimulating factor (G‐CSF) is commonly used to maintain it. We reviewed all newly diagnosed HL patients who were treated at our institution between 1996 and 2005. Fifty‐nine patients received adriamycin, bleomycin, vinblastine, and dacarbazine (ABVD) chemotherapy with no dose reductions, treatment delays, and without G‐CSF, regardless of absolute neutrophil count (ANC). The median ANC on all ABVD treatment days (n = 658) was 0·925 × 109/l, and was <0·5 × 109/l on 26% of treatment days. Median normalised ABVD dose–intensity was 99·1% (range, 93–100%) and median cycle duration was 28·2 d. Incidence of bleomycin lung toxicity was 1·6%, 0·44% treatments were complicated by febrile neutropenia, and no secondary malignancies have occurred (median follow‐up 48 months; range, 11–130 months). Five‐year event‐free (EFS) and overall survival (OS) were 92·9% and 97·4% respectively. Furthermore, the 5‐year EFS and OS (87·4% and 94·1% respectively) for advanced stage patients compared favourably with a similar ABVD patient group who received routine prophylactic G‐CSF (n = 23) with EFS 80·0% and OS 91·3% (P = 0·46 and 0·67 respectively). Our experience suggests that ABVD may be safely and effectively administered at >99% dose–intensity without G‐CSF support, regardless of the ANC.
The 13q and 11q B‐cell chronic lymphocytic leukaemia‐associated regions derive from a common ancestral region in the zebrafish
Authors: Auer Rebecca L. , Riaz Sophia , Cotter Finbarr E. 
Published: May 2007

SummaryLoss of the long arm of chromosomes 11 and 13 is the most consistent cytogenetic abnormalities for patients with B‐cell chronic lymphocytic leukaemia (B‐CLL). They suggest the presence of as yet unidentified tumour suppressor genes within well‐defined minimal‐deleted regions (MinDRs). We have identified 38 orthologues of the human genes in MinDRs in zebrafish cDNA and syntenic regions for the human deletions in the zebrafish genome. One region on chromosome 9 in the zebrafish genome is of potential interest. Within chromosome 9, five genes and two microRNAs were identified with shared synteny to the MinDRs in B‐CLL (two genes to human chromosome 11, three to human chromosome 13 and two chromosome 13 microRNAs). The critical region on zebrafish chromosome 9 maps to the MinDR for both human chromosomes, suggesting a common ancestry for B‐CLL tumour suppressor genes. Target‐selected mutagenesis to identify zebrafish mutants with knock‐outs of genes in this region will allow analysis of their in vivo potential for lymphoproliferation and may define causative genes for B‐CLL within human chromosomes 11q and 13q. Our study provides an explanation for involvement of both 11q and 13q in B‐CLL and the potential to develop animal models for this common lymphoproliferative disorder.
Serum leptin, oxidized low density lipoprotein and plasma asymmetric dimethylarginine levels and their relationship with dyslipidaemia in adolescent girls with polycystic ovary syndrome
Authors: Demirel Fatma , Bideci Aysun , Cinaz Peyami , Çamurdan M. Orhun , Biberoğlu Gürsel , Yesilkaya Ediz , Hasanoğlu Alev 
Published: May 2007

SummaryObjective  The aim of this study was to investigate serum leptin, oxidized low density lipoprotein (ox‐LDL) and asymmetric dimethylarginine (ADMA) levels and their interaction with dyslipidaemia in adolescents with polycystic ovary syndrome (PCOS).Patients and design  The study group consisted of 23 obese (obPCOS) and 21 nonobese girls with PCOS (nPCOS), and 31 lean healthy controls. PCOS was defined by the National Institutes of Health (NIH) criteria as the presence of chronic oligoanovulation and hyperandrogenism. Fasting leptin, ox‐LDL, ADMA and detailed lipid‐lipoprotein profile were determined. Atherogenic index (AI) was calculated as [Total cholesterol − HDL cholesterol/HDL cholesterol]. Logarithmic transformations were made for ox‐LDL.Results  Total cholesterol, triglycerides, LDL cholesterol, very low density lipoprotein (VLDL) cholesterol, apolipoprotein B, lipoprotein A levels and AI were higher and apolipoprotein AI was lower in obPCOS compared to those in controls (P < 0·05). LDL cholesterol, apolipoprotein B and lipoprotein A levels were higher in nPCOS compared to controls (P < 0·05). ADMA and ox‐LDL levels did not differ in the three groups. Leptin was significantly higher in obPCOS compared with that in the other two groups (P < 0·001) and it was correlated with triglycerides (r = 0·62), VLDL cholesterol (r = 0·45), lipoprotein A (r = 0·38) and AI (r = 0·43) in the PCOS group (P < 0·05).Conclusion  Our data demonstrate that ADMA and ox‐LDL levels in adolescent PCOS subjects were not different than those in controls. Abnormal lipid profile was shown in obese and nonobese girls with PCOS and leptin was related with these lipid abnormalities in the PCOS subjects.
Cardiac biomarkers and survival in haemodialysis patients
Authors: Sommerer C. , Beimler J. , Schwenger V. , Heckele N. , Katus H. A. , Giannitsis E. , Zeier M. 
Published: May 2007

AbstractBackground  In dialysis patients, cardiac troponin T (cTNT) is often elevated despite the absence of acute myocardial ischaemia, and amino‐terminal pro‐B‐natriuretic peptide (NT‐proBNP) is markedly higher compared to non‐haemodialysis patients. In a longitudinal observation, we evaluated the association of cTNT and NT‐proBNP on cardiovascular morbidity and mortality in haemodialysis patients with and without fluid overload.Materials and methods  Plasma cTNT levels of 134 haemodialysis patients were measured before and after a dialysis session by 3rd generation electro‐chemoluminiscence immunoassay. NT‐proBNP was determined using a polyclonal antibody recognizing the N‐terminal fragment of BNP (Elecsys autoanalyzer 2010, Roche Diagnostics, Mannheim, Germany). Volume status was determined by a clinical score system. Cardiovascular morbidity and mortality were assessed over a follow‐up period of 36 months.Results  Plasma cTNT > 0·03 ng mL−1 was found in 39·6% of all patients. Patients with hypervolaemia had significantly higher cTNT levels compared to euvolaemic patients (median 0·054 ng mL−1, interquartile range 0·019–0·153 vs. 0·005 ng mL−1, < 0·001–0·034; P < 0·001). All haemodialysis patients had excessively high levels of NT‐proBNP (median 4524; interquartile range 2000–10 250 pg mL−1), and NT‐proBNP was significantly higher in hypervolaemic haemodialysis patients (11 988, 5307–19 242) compared to euvolaemic haemodialysis patients (3247, 1619–5574); P < 0·001. Receiver operator curves showed a threshold of cTNT > 0·026 ng mL−1 and NT‐proBNP > 5300 pg mL−1 as predictors of hypervolaemia. Asymptomatic chronic haemodialysis patients with cTNT > 0·026 ng mL−1 and NT‐proBNP > 5300 pg mL−1 were more likely to die due to cardiac events in the follow‐up period. Multivariate analysis documented that elevated cTNT and NT‐proBNP levels were highly predictive for cardiovascular events.Conclusions  Plasma levels of cTNT are elevated in approximately 40% and NT‐proBNP levels in 100% of asymptomatic chronic haemodialysis patients. Both parameters depend on volume status. Increased NT‐proBNP and cTNT are strongly associated with adverse outcome in end‐stage renal disease patients undergoing haemodialysis, and are a useful tool for risk stratification in chronic haemodialysis patients.
Co‐administration of ezetimibe and simvastatin in acute myocardial infarction
Authors: Chenot F. , Montant P. F. , Marcovitch O. , Blaimont M. , De Meester A. , Descamps O. S. 
Published: May 2007

AbstractBackground  Recent trials in acute myocardial infarction indicate that intensive and early statin therapy that lowers low‐density lipoprotein cholesterol (LDL‐C) to ≤ 70 mg dL−1 is beneficial. The combination of statins with ezetimibe, a newly developed cholesterol‐absorption inhibitor, can lead to a further reduction in LDL‐C of up to 26%. In this study, we examined the rapidity and intensity of the lipid‐lowering effect of ezetimibe co‐administered with simvastatin immediately after myocardial infarction.Materials and methods  Sixty patients admitted for acute myocardial infarction were randomized to receive either simvastatin 40 mg (SIMVA), a combination of simvastatin 40 mg and ezetimibe 10 mg (EZE/SIMVA), or no lipid‐lowering drugs (NLLD) and had their lipid levels assessed 2, 4 and 7 days later.Results  At baseline, cardiovascular risk factors were similar in all three groups [mean (SD) LDL‐C of 141 (36) mg dL−1]. At days 2 , 4 and 7 there was no significant change in mean LDL‐C levels in the NLLD group (−10%, −6%, and −9%, all P > 0·09), while there were significant reductions with SIMVA (−15%, −27%, and −25%, respectively, all P < 0·001 vs. day 0) and even greater reductions with co‐administration of EZE/SIMVA (−27%, −41%, and −51%, respectively, all P < 0·001 vs. day 0). The percentages of patients achieving LDL‐C below 70 mg dL−1 at days 4 and 7 were substantially greater with EZE/SIMVA (45% and 55%, respectively) than with SIMVA (5% and 10%, respectively), while no NLLD patient reached this goal. Triglyceride levels showed a progressive increase in the NLLD group (+45% at day 7, P < 0·05 vs. day 0), no change in the SIMVA group, but a decrease in the EZE/SIMVA group (−17% at day 7, P < 0·05 vs. day 0). No significant difference in HDL‐C levels, tolerability, or clinical events was observed between the three groups.Conclusions  The co‐administration of ezetimibe 10 mg with simvastatin 40 mg, by inhibiting cholesterol absorption and production, allowed more patients with acute myocardial infarction to reach LDL‐C ≤ 70 mg dL−1 as early as the fourth day of treatment. The effects of such rapid and intense reduction in LDL‐C on cardiovascular morbidity and mortality need to be evaluated in future clinical endpoint studies.