bluuebunny/crossref_metadata_2025_split huggingface dataset:
Learning gene regulatory networks from gene expression measurements using non-parametric molecular kinetics
Authors: Äijö Tarmo , Lähdesmäki Harri 
Published: August 2009

Abstract
Motivation: Regulation of gene expression is fundamental to the operation of a cell. Revealing the structure and dynamics of a gene regulatory network (GRN) is of great interest and represents a considerably challenging computational problem. The GRN estimation problem is complicated by the fact that the number of gene expression measurements is typically extremely small when compared with the dimension of the biological system. Further, because the gene regulation process is intrinsically complex, commonly used parametric models can provide too simple description of the underlying phenomena and, thus, can be unreliable. In this article, we propose a novel methodology for the inference of GRNs from time-series and steady-state gene expression measurements. The presented framework is based on the use of Bayesian analysis with ordinary differential equations (ODEs) and non-parametric Gaussian process modeling for the transcriptional-level regulation.
Results: The performance of the proposed structure inference method is evaluated using a recently published in vivo dataset. By comparing the obtained results with those of existing ODE- and Bayesian-based inference methods we demonstrate that the proposed method provides more accurate network structure learning. The predictive capabilities of the method are examined by splitting the dataset into a training set and a test set and by predicting the test set based on the training set.
Availability: A MATLAB implementation of the method will be available from http://www.cs.tut.fi/~aijo2/gp upon publication
Contact: harri.lahdesmaki@tut.fi
Supplementary information: Supplementary data are available at Bioinformatics online.
digeR: a graphical user interface R package for analyzing 2D-DIGE data
Authors: Fan Yue , Murphy T. Brendan , Watson R. William G. 
Published: August 2009

Abstract
Summary: 2D Difference In-Gel Electrophoresis (2D-DIGE) or 2D gel technology is being used as a routine proteomics technique for biomarker discovery. Analyzing such high-dimensional data requires multivariate analysis techniques to be applied. In addition, protein post-translational modification (PTM) information from the 2D gel data is usually overlooked. We report on an R package, digeR, with an easy to use graphical user interface for analyzing 2D-DIGE (2D gel) data. It provides a tool for visually looking for potential PTM changes from different biological states and support biomarker discovery through multivariate analysis techniques.
Availability: digeR package is freely available from the CRAN: http://cran.r-project.org/web/packages/digeR/index.html.
Contact: yue.fan@ucd.ie
Supplementary information: Supplementary data are available at Bioinformatics online.
Transcript Profiling Provides Evidence of Functional Divergence and Expression Networks among Ribosomal Protein Gene Paralogs inBrassica napus
Authors: Whittle Carrie A. , Krochko Joan E. 
Published: August 2009

AbstractThe plant ribosome is composed of 80 distinct ribosomal (r)-proteins. In Arabidopsis thaliana, each r-protein is encoded by two or more highly similar paralogous genes, although only one copy of each r-protein is incorporated into the ribosome. Brassica napus is especially suited to the comparative study of r-protein gene paralogs due to its documented history of genome duplication as well as the recent availability of large EST data sets. We have identified 996 putative r-protein genes spanning 79 distinct r-proteins in B. napus using EST data from 16 tissue collections. A total of 23,408 tissue-specific r-protein ESTs are associated with this gene set. Comparative analysis of the transcript levels for these unigenes reveals that a large fraction of r-protein genes are differentially expressed and that the number of paralogs expressed for each r-protein varies extensively with tissue type in B. napus. In addition, in many cases the paralogous genes for a specific r-protein are not transcribed in concert and have highly contrasting expression patterns among tissues. Thus, each tissue examined has a novel r-protein transcript population. Furthermore, hierarchical clustering reveals that particular paralogs for nonhomologous r-protein genes cluster together, suggesting that r-protein paralog combinations are associated with specific tissues in B. napus and, thus, may contribute to tissue differentiation and/or specialization. Altogether, the data suggest that duplicated r-protein genes undergo functional divergence into highly specialized paralogs and coexpression networks and that, similar to recent reports for yeast, these are likely actively involved in differentiation, development, and/or tissue-specific processes.
The efficacy and safety of a third anti‐TNF monoclonal antibody in Crohn’s disease after failure of two other anti‐TNF antibodies
Authors: ALLEZ M. , VERMEIRE S. , MOZZICONACCI N. , MICHETTI P. , LAHARIE D. , LOUIS E. , BIGARD M.‐A. , HÉBUTERNE X. , TRETON X. , KOHN A. , MARTEAU P. , CORTOT A. , NICHITA C. , VAN ASSCHE G. , RUTGEERTS P. , LÉMANN M. , COLOMBEL J.‐F. 
Published: August 2009

SummaryBackground  Adalimumab (ADA) and certolizumab pegol (CZP) have demonstrated efficacy in Crohn’s disease (CD) patients previously treated with infliximab (IFX).Aim  To assess the efficacy and tolerability of a third anti‐TNF in CD after failure of and/or intolerance to two different anti‐TNF antibodies.Methods  Crohn’s disease patients who received ADA or CZP after loss of response and/or intolerance to two anti‐TNF agent were included in this retrospective study. Data were collected using a standardized questionnaire. Clinical response, duration, safety and reasons for discontinuation were assessed.Results  Sixty‐seven patients treated with CZP (n = 40) or ADA (n = 27) were included. A clinical response was observed in 41 (61%) at week 6 and 34 patients (51%) at week 20. The probability of remaining under treatment at 3 months, 6 months and 9 months was 68%, 60% and 45%, respectively. At the end of follow‐up, the third anti‐TNF had been stopped in 36 patients for intolerance (n = 13), or failure (n = 23). Two deaths were observed.Conclusions  The treatment with a third anti‐TNF (CZP or ADA) agent of CD patients, who have experienced loss of response and/or intolerance to two anti‐TNF antibodies, has favourable short‐term and long‐term efficacy. It is an option to be considered in patients with no other therapeutic options.
Mercaptopurine rescue after azathioprine‐induced liver injury in inflammatory bowel disease
Authors: BERMEJO F. , LÓPEZ‐SANROMÁN A. , ALGABA A. , VAN‐DOMSELAAR M. , GISBERT J. P. , GARCÍA‐GARZÓN S. , GARRIDO E. , PIQUERAS B. , DE LA POZA G. , GUERRA I. 
Published: August 2009

SummaryBackground  Azathioprine (AZA) liver toxicity arises in approximately 3% of inflammatory bowel disease patients and may result in treatment discontinuation.Aim  To describe the tolerance to mercaptopurine (MP) in patients with previous AZA‐related liver injury.Methods  Retrospective description of 31 patients (14 Crohn’s, 17 ulcerative colitis), in which AZA therapy was interrupted because of liver injury, with MP started as alternative therapy.Results  Mean AZA dose was 2.2 ± 0.4 mg·kg/day. Median (interquartile range) of AZA exposure when liver injury was detected was 2 months (1–5.2). The type of AZA‐related injury was cytolitic in 32%, cholestatic in 39% and mixed in 29%. After a median of 2.5 months (0.7–5.2), the therapy was switched to MP at a mean dose of 1.3 ± 0.2 mg·kg/day. Median of follow‐up of MP therapy was 32 months (8–54). In 87.1% of patients (95%CI: 70–96%), MP was tolerated without further liver injury; of these, 77.4% tolerated full MP doses and 9.7% tolerated lower doses. In a further cohort of 12.9% of patients, (95%CI: 3–29%), liver injury reappeared (two cholestasis, two mixed), 1–3 months after the onset of MP exposure.Conclusion  The administration of MP is a good alternative in patients with AZA‐related liver injury, before thiopurines are definitely discarded.
A novel missense mutation in SLC40A1 results in resistance to hepcidin and confirms the existence of two ferroportin‐associated iron overload diseases
Authors: Létocart Emilie , Le Gac Gérald , Majore Silvia , Ka Chandran , Radio Francesca C. , Gourlaouen Isabelle , De Bernardo Carmelilia , Férec Claude , Grammatico Paola 
Published: August 2009

SummaryFerroportin‐related iron overload disease differs from haemochromatosis in that it has a dominant mode of inheritance and is usually associated with macrophage iron sequestration. However, it is thought that mutations with opposite effects on protein functions, i.e. loss‐of‐function versus gain‐of‐function mutations, are responsible for variable phenotype presentations. The present study investigated the functional relevance of a novel ferroportin variant: the c.1502 A>G transition, which changes amino acid 501 from tyrosine to cysteine (p.Y501C). This novel variant was identified in a pedigree originating from Central Italy and, although an intra‐familial phenotype heterogeneity was observed, it co‐segregated with an iron overload picture similar to that of the HFE‐related typical haemochromatosis. In cultured cells, the p.Y501C mutant protein reached the plasma membrane and retained a full iron export ability. By contrast, it was resistant to inhibition by hepcidin. These findings confirm that certain ferroportin mutations compromise the activity of hepcidin in iron homeostasis, mimicking hepcidin deficiency as described in all types of hemochromatosis.
Allogeneic haemopoietic stem cell transplantation in children: what alternative donor should we choose when no matched sibling is available?
Authors: Hough Rachael , Cooper Nicola , Veys Paul 
Published: August 2009

SummaryAllogeneic haemopoietic stem cell transplantation has provided curative therapy for life‐threatening malignant and non‐malignant diseases in children for over 40 years. Only 25% of children in whom an allograft is indicated have the ideal option of a human leucocyte antigen‐identical sibling donor. Substantial advances in the use of alternative donors (unrelated volunteer donors, haploidentical family donors and unrelated umbilical cord blood donors) now make it possible for almost all children to benefit from this life‐saving treatment. Each donor choice is associated with distinct advantages and disadvantages, which have greater or lesser importance in different diseases. We review the current status of alternative donor transplantation for haematological malignancies, primary immunodeficiencies, inherited metabolic disorders and bone marrow failure syndromes and outline the current UK consensus donor selection algorithms for these disease groups.
Preclinical activity of 8‐chloroadenosine with mantle cell lymphoma: roles of energy depletion and inhibition of DNA and RNA synthesis
Authors: Dennison Jennifer B. , Balakrishnan Kumudha , Gandhi Varsha 
Published: August 2009

Summary8‐Chloroadenosine (8‐Cl‐Ado), an RNA‐directed nucleoside analogue, is currently under evaluation in phase I clinical trials for treatment of chronic lymphocytic leukaemia. In the current study, the efficacy of 8‐Cl‐Ado was evaluated using mantle cell lymphoma (MCL) cell lines: Granta 519, JeKo, Mino, and SP‐53. After continuous exposure to 10 μmol/l 8‐Cl‐Ado for 24 h, loss of mitochondrial transmembrane potential and poly [adenosine diphosphate (ADP)‐ribose] polymerase (PARP) cleavage were detected in three of four cell lines. Reduced ATP levels (30–60% reduction) and concurrent 8‐Cl‐ATP accumulation were highly associated with cell death (P < 0·01). The intracellular 8‐Cl‐ATP concentrations were also highly correlated with inhibition of global transcription (50–90%, r2 = 0·90, P < 0·01). However, the inhibition of transcription only accounted for 30–40% of cell death as determined by equivalent inhibition with actinomycin D. Likewise, short‐lived mRNAs, those encoding cyclin D1 and Mcl‐1, were not consistently reduced after treatment. Unique to MCL as compared to other haematological malignancies, 8‐Cl‐Ado inhibited the rates of DNA synthesis and selectively depleted dATP pools (50–80%). We conclude that the DNA and RNA directed actions of 8‐Cl‐Ado in combination with depleted energetics may promote cell death and inhibit growth of MCL cell lines.
High incidence of haemophagocytic syndrome following umbilical cord blood transplantation for adults
Authors: Takagi Shinsuke , Masuoka Kazuhiro , Uchida Naoyuki , Ishiwata Kazuya , Araoka Hideki , Tsuji Masanori , Yamamoto Hisashi , Kato Daisuke , Matsuhashi Yoshiko , Kusumi Eiji , Ota Yasunori , Seo Sachiko , Matsumura Tomoko , Matsuno Naofumi , Wake Atsushi , Miyakoshi Shigesaburo , Makino Shigeyoshi , Ohashi Kenichi , Yoneyama Akiko , Taniguchi Shuichi 
Published: August 2009

SummaryUmbilical cord blood transplantation (CBT) is widely accepted, but one critical issue for adult patients is a low engraftment rate, of which one cause is haemophagocytic syndrome (HPS). We aimed to identify the contribution of HPS to engraftment failure after CBT, following preparative regimens containing fludarabine phosphate, in 119 patients (median age, 55 years; range; 17–69 years) with haematological diseases. Graft‐versus‐host disease prophylaxis comprised continuous infusion of a calcineurin inhibitor with or without mycophenolate mofetil. Of the 119 patients, 20 developed HPS within a median of 15 d (cumulative incidence; 16·8%) and 17 of them did so before engraftment. Donor‐dominant chimaerism was confirmed in 16 of 18 evaluable patients with HPS. Despite aggressive interventions including corticosteroid, ciclosporin, high‐dose immunoglobulin and/or etoposide, engraftment failed in 14 of 18 patients. Of these 14 patients, four received second rescue transplantation and all resulted in successful engraftment. Overall survival rates significantly differed between patients with and without HPS (15·0% vs. 35·4%; P < 0·01). Univariate and multivariate analysis identified having fewer infused CD34+ cells as a significant risk factor for the development of HPS (P = 0·01 and 0·006, respectively). We concluded that engraftment failure closely correlated with HPS in our cohort, which negatively impacted overall survival after CBT.
Aspirin induces apoptosis in mesenchymal stem cells requiring Wnt/β‐catenin pathway
Authors: Deng L. , Hu S. , Baydoun A. R. , Chen J. , Chen X. , Cong X. 
Published: August 2009

AbstractBackground and Objectives:  Mesenchymal stem cells (MSC) are multipotent progenitor cells that are have found use in regenerative medicine. We have previously observed that aspirin, a widely used anti‐inflammatory drug, inhibits MSC proliferation. Here we have aimed to elucidate whether aspirin induces MSC apoptosis and whether this is modulated through the Wnt/β‐catenin pathway.Materials and methods:  Apoptosis of MSCs was assessed using Hoechst 33342 dye and an Annexin V–FITC/PI Apoptosis Kit. Expression of protein and protein phosphorylation were investigated using Western blot analysis. Caspase‐3 activity was detected by applying a caspase‐3/CPP32 Colorimetric Assay Kit.Results:  In these MSCs, aspirin induced morphological changes characteristic of apoptosis, cytochrome c release from mitochondria, and caspase‐3 activation. Stimulating the Wnt/β‐catenin pathway by both Wnt 3a and GSK‐3β inhibitors (LiCl and SB 216763), blocked aspirin‐induced apoptosis and protected mitochondrial function, as demonstrated by decreased cytochrome c release and caspase‐3 activity. Aspirin initially caused a time‐dependent decrease in COX‐2 expression but subsequently, and unexpectedly, elevated the latter. Stimulation of COX‐2 expression by aspirin was further enhanced following stimulation of the Wnt/β‐catenin pathway. Application of the COX‐2 inhibitor NS‐398 suppressed elevated COX‐2 expression and promoted aspirin‐induced apoptosis.Conclusion:  These results demonstrate that the Wnt/β‐catenin pathway is a key modulator of aspirin‐induced apoptosis in MSCs by regulation of mitochrondrial/caspase‐3 function. More importantly, our findings suggest that aspirin may influence MSC survival under certain conditions; therefore, it should be used with caution when considering regenerative MSC transplantation in patients with concomitant chronic inflammatory diseases such as arthritis.
Soil‐gas diffusivity in large soil monoliths
Authors: Lange S. F. , Allaire S. E. , Rolston D. E. 
Published: August 2009

SummaryThe variability of gas diffusion in soil is not well known, but is important for assessing greenhouse gas emissions, soil decontamination, oxidation in soil and plant and root respiration. The goal of this study was to assess small‐scale variability of the relative soil‐gas diffusivity (Ds / Do, msoil air) using large intact soil monoliths and to compare Ds / Do calculation methods. Neon (Ne) was maintained constant at the lower boundary of three monoliths of two soils (a sand and an organic soil). Ne concentration was measured at large spatial and temporal frequencies. Calculation methods included the use of average concentration, and average Ds / Do per horizon, per section, or for the entire soil profile. Considering all sections of the monoliths, Ds / Do varied from 3.5 × 10−3 to 1.2 × 10−1 for the Ap horizon and from 4.8 × 10−3 to 8.3 × 10−1 for the Bf horizon in the sand and from 1.0 × 10−3 to 7.9 × 10−3 for the Ohp horizon and from 2.4 × 10−4 to 7.7 × 10−2 for the Of horizon in the organic soil. For the entire soil profile, variations in Ds / Do between monoliths reached 125% in the sand and 56% in the organic soil. The Ds / Do calculation method influenced the apparent variability (CV) of Ds / Do and, to a lesser extent, Ds / Do values of the overall soil profile. Differences in Ds / Do between monoliths could not be explained solely by the variability of total soil porosity and air‐filled porosity. Soil macroporosity (cracks and earthworm burrows) and layering greatly influenced variability of gas movement. Thus, the choice of sampling procedure, calculation method and modelling must be governed by the scale of the processes of interest and soil variability attributes.
Autism spectrum disorders in genetic syndromes: implications for diagnosis, intervention and understanding the wider autism spectrum disorder population
Authors: Moss J. , Howlin P. 
Published: August 2009

AbstractBackground An emerging literature on behavioural phenotypes has highlighted apparent associations between autism spectrum disorders (ASDs) or ASD‐related phenomenology and a number of different genetically determined syndromes.Method A systematic review of the current literature regarding the association with ASD and ASD characteristics was conducted in the following syndrome groups: Fragile X, Rett, Tuberous Sclerosis Complex, Down, Angelman, CHARGE and Phenylketonuria. Specific consideration was given to the role of intellectual disability in assessing the association between ASD and these syndrome groups.Results The review highlights that while formal diagnostic assessments may indicate an association between ASD and specific syndrome groups, detailed investigation has revealed subtle but qualitative differences in the presentation of ASD‐like phenomenology in particular syndrome groups. The degree of ID of the individual clearly has a role to play with regard to the development and presentation of ASD‐like characteristics, and caution should be taken when assessing ASD symptomatology in genetically determined syndromes associated with severe ID. However, degree of ID cannot solely account for the heightened prevalence of ASD characteristics in some specific syndrome groups.Conclusions There is a need for caution in interpreting the significance of superficial similarities between ASD and the behavioural phenotypes of certain genetically determined syndromes. However, recognition of ASD‐like characteristics (even where a true diagnosis of ASD may not be relevant) in individuals with genetic syndromes is crucial in ensuring that individuals receive appropriate behavioural management and educational placement. Further research in this field requires fine‐grained investigation of behavioural phenomenology within individual syndrome groups.
Time‐lapse FRET microscopy using fluorescence anisotropy
Authors: MATTHEWS D.R. , CARLIN L.M. , OFO E. , BARBER P.R. , VOJNOVIC B. , IRVING M. , NG T. , AMEER‐BEG S.M. 
Published: August 2009

SummaryWe present recent data on dynamic imaging of Rac1 activity in live T‐cells. Förster resonance energy transfer between enhanced green and monomeric red fluorescent protein pairs which form part of a biosensor molecule provides a metric of this activity. Microscopy is performed using a multi‐functional high‐content screening instrument using fluorescence anisotropy to provide a means of monitoring protein–protein activity with high temporal resolution. Specifically, the response of T‐cells upon interaction of a cell surface receptor with an antibody coated multi‐well chamber was measured. We observed dynamic changes in the activity of the biosensor molecules with a time resolution that is difficult to achieve with traditional methodologies for observing Förster resonance energy transfer (fluorescence lifetime imaging using single photon counting or frequency domain techniques) and without spectral corrections that are normally required for intensity based methodologies.
TLR9 Activation Increases TAP‐Independent Vesicular MHC Class I Processing In vivo
Authors: Chen L. , Jondal M. 
Published: August 2009

AbstractCross‐presentation of soluble protein antigens on major histocompatibility complex (MHC) class I by dendritic cells (DC) can occur in vesicular, endolysosomal compartments and be either dependent or independent of TAP peptide transporters. Here we investigate if an immunostimulatory CpG oligodeoxynucleotide can increase the activity in a TAP‐independent endolysosomal vesicular pathway (el‐VP) in vivo as we have earlier found in in vitro cultured DC. We use the in vivo response of CFSE labelled OT‐1 T cells, transgenic for a T‐cell receptor (TCR) that recognizes an ovalbumin (OVA)‐derived peptide (SIINFEKL) presented by H‐2Kb, transferred into TAP1−/− mice, as a functional read‐out for activity in the el‐VP. We have found a poor OT‐1 T‐cell response to soluble OVA which, however, could be strongly enhanced by the simultaneous administration of CpG. This increased responsiveness required both the endolysosomal cathepsin S (CatS) and Toll like receptor (TLR)9, the CpG receptor, both of which are present in the el‐VP. Confocal microscopy demonstrated a co‐localization of H‐2Kb/SIINFEKL and the endolysosomal marker LAMP1 in CD11c positive DC which was markedly increased by CpG administration. No complexes were found in the ER and cis‐Golgi compartments in TAP1−/− mice, indicating the lack of classical MHC‐I processing. In DC isolated from CatS−/− mice the opposite was found, complexes were present in the ER but not in the el‐VP. We conclude that in vivo activation of TLR9 by CpG increases the efficiency of TAP independent el‐VP and that this might contribute to the potent adjuvant activity of this type of compound. The cellular mechanisms remain to be established.