bluuebunny/crossref_metadata_2025_split huggingface dataset:
TransportTP: A two-phase classification approach for membrane transporter prediction and characterization
Authors: Li Haiquan , Benedito Vagner A , Udvardi Michael K , Zhao Patrick Xuechun 
Published: December 2009

AbstractBackgroundMembrane transporters play crucial roles in living cells. Experimental characterization of transporters is costly and time-consuming. Current computational methods for transporter characterization still require extensive curation efforts, especially for eukaryotic organisms. We developed a novel genome-scale transporter prediction and characterization system called TransportTP that combined homology-based and machine learning methods in a two-phase classification approach. First, traditional homology methods were employed to predict novel transporters based on sequence similarity to known classified proteins in the Transporter Classification Database (TCDB). Second, machine learning methods were used to integrate a variety of features to refine the initial predictions. A set of rules based on transporter features was developed by machine learning using well-curated proteomes as guides.ResultsIn a cross-validation using the yeast proteome for training and the proteomes of ten other organisms for testing, TransportTP achieved an equivalent recall and precision of 81.8%, based on TransportDB, a manually annotated transporter database. In an independent test using the Arabidopsis proteome for training and four recently sequenced plant proteomes for testing, it achieved a recall of 74.6% and a precision of 73.4%, according to our manual curation.ConclusionsTransportTP is the most effective tool for eukaryotic transporter characterization up to date.
Web-based interrogation of gene expression signatures using EXALT
Authors: Wu Jun , Qiu Qingchao , Xie Lu , Fullerton Joseph , Yu Jian , Shyr Yu , George Alfred L , Yi Yajun 
Published: December 2009

Abstract

Background
Widespread use of high-throughput techniques such as microarrays to monitor gene expression levels has resulted in an explosive growth of data sets in public domains. Integration and exploration of these complex and heterogeneous data have become a major challenge.

Results
The EXALT (EX pression signature A naL ysis T ool) online program enables meta-analysis of gene expression profiles derived from publically accessible sources. Searches can be executed online against two large databases currently containing more than 28,000 gene expression signatures derived from GEO (Gene Expression Omnibus) and published expression profiles of human cancer. Comparisons among gene expression signatures can be performed with homology analysis and co-expression analysis. Results can be visualized instantly in a plot or a heat map. Three typical use cases are illustrated.

Conclusions
The EXALT online program is uniquely suited for discovering relationships among transcriptional profiles and searching gene expression patterns derived from diverse physiological and pathological settings. The EXALT online program is freely available for non-commercial users from http://seq.mc.vanderbilt.edu/exalt/.
The Golgi α-1,6 mannosyltransferase KlOch1p of Kluyveromyces lactis is required for Ca2+/calmodulin-based signaling and for proper mitochondrial functionality
Authors: Zanni Elena , Farina Francesca , Ricci Antonella , Mancini Patrizia , Frank Claudio , Palleschi Claudio , Uccelletti Daniela 
Published: December 2009

Abstract

Background
Protein N-glycosylation is a relevant metabolic pathway in eukaryotes and plays key roles in cell processes. In yeasts, outer chain branching is initiated in the Golgi apparatus by the alpha-1,6-mannosyltransferase Och1p.

Results
Here we report that, in Kluyveromyces lactis, this glycosyltransferase is also required to maintain functional mitochondria and calcium homeostasis. Cells carrying a mutation in KlOCH1 gene showed altered mitochondrial morphology, increased accumulation of ROS and reduced expression of calcium signalling genes such as calmodulin and calcineurin. Intracellular calcium concentration was also reduced in the mutant cells with respect to the wild type counterparts.
Phenotypes that occur in cells lacking the alpha-1,6-mannosyltransferase, including oxidative stress and impaired mitochondria functionality, were suppressed by increased dosage of KlCmd1p. This, in turn, acts through the action of calcineurin.

Conclusions
Proper functioning of the alpha-1,6-mannosyltransferase in the N-glycosylation pathway of K. lactis is required for maintaining normal calcium homeostasis; this is necessary for physiological mitochondria dynamics and functionality.
Mechanism of primitive duct formation in the pancreas and submandibular glands: a role for SDF-1
Authors: Hick Anne-Christine , van Eyll Jonathan M , Cordi Sabine , Forez Céline , Passante Lara , Kohara Hiroshi , Nagasawa Takashi , Vanderhaeghen Pierre , Courtoy Pierre J , Rousseau Guy G , Lemaigre Frédéric P , Pierreux Christophe E 
Published: December 2009

Abstract

Background
The exocrine pancreas is composed of a branched network of ducts connected to acini. They are lined by a monolayered epithelium that derives from the endoderm and is surrounded by mesoderm-derived mesenchyme. The morphogenic mechanisms by which the ductal network is established as well as the signaling pathways involved in this process are poorly understood.

Results
By morphological analyzis of wild-type and mutant mouse embryos and using cultured embryonic explants we investigated how epithelial morphogenesis takes place and is regulated by chemokine signaling. Pancreas ontogenesis displayed a sequence of two opposite epithelial transitions. During the first transition, the monolayered and polarized endodermal cells give rise to tissue buds composed of a mass of non polarized epithelial cells. During the second transition the buds reorganize into branched and polarized epithelial monolayers that further differentiate into tubulo-acinar glands. We found that the second epithelial transition is controlled by the chemokine Stromal cell-Derived Factor (SDF)-1. The latter is expressed by the mesenchyme, whereas its receptor CXCR4 is expressed by the epithelium. Reorganization of cultured pancreatic buds into monolayered epithelia was blocked in the presence of AMD3100, a SDF-1 antagonist. Analyzis of sdf1 and cxcr4 knockout embryos at the stage of the second epithelial transition revealed transient defective morphogenesis of the ventral and dorsal pancreas. Reorganization of a globular mass of epithelial cells in polarized monolayers is also observed during submandibular glands development. We found that SDF-1 and CXCR4 are expressed in this organ and that AMD3100 treatment of submandibular gland explants blocks its branching morphogenesis.

Conclusion
In conclusion, our data show that the primitive pancreatic ductal network, which is lined by a monolayered and polarized epithelium, forms by remodeling of a globular mass of non polarized epithelial cells. Our data also suggest that SDF-1 controls the branching morphogenesis of several exocrine tissues.
Transcriptional profile of Pseudomonas syringae pv. phaseolicola NPS3121 in response to tissue extracts from a susceptible Phaseolus vulgarisL. cultivar
Authors: Hernández-Morales Alejandro , De la Torre-Zavala Susana , Ibarra-Laclette Enrique , Hernández-Flores José Luis , Jofre-Garfias Alba Estela , Martínez-Antonio Agustino , Álvarez-Morales Ariel 
Published: December 2009

AbstractBackgroundPseudomonas syringaepv. phaseolicola is a Gram-negative plant-pathogenic bacterium that causes "halo blight" disease of beans (Phaseolus vulgarisL.). This disease affects both foliage and pods, and is a major problem in temperate areas of the world. Although several bacterial genes have been determined as participants in pathogenesis, the overall process still remains poorly understood, mainly because the identity and function of many of the genes are largely unknown. In this work, a genomic library ofP. syringaepv. phaseolicola NPS3121 was constructed and PCR amplification of individual fragments was carried out in order to print a DNA microarray. This microarray was used to identify genes that are differentially expressed when bean leaf extracts, pod extracts or apoplastic fluid were added to the growth medium.ResultsTranscription profiles show that 224 genes were differentially expressed, the majority under the effect of bean leaf extract and apoplastic fluid. Some of the induced genes were previously known to be involved in the first stages of the bacterial-plant interaction and virulence. These include genes encoding type III secretion system proteins and genes involved in cell-wall degradation, phaseolotoxin synthesis and aerobic metabolism. On the other hand, most repressed genes were found to be involved in the uptake and metabolism of iron.ConclusionThis study furthers the understanding of the mechanisms involved, responses and the metabolic adaptation that occurs during the interaction ofP. syringaepv. phaseolicola with a susceptible host plant.
Nuclear factor I-A represses expression of the cell adhesion molecule L1
Authors: Schneegans Tanja , Borgmeyer Uwe , Hentschke Moritz , Gronostajski Richard M , Schachner Melitta , Tilling Thomas 
Published: December 2009

Abstract

Background
The neural cell adhesion molecule L1 plays a crucial role in development and plasticity of the nervous system. Neural cells thus require precise control of L1 expression.

Results
We identified a full binding site for nuclear factor I (NFI) transcription factors in the regulatory region of the mouse L1 gene. Electrophoretic mobility shift assay (EMSA) showed binding of nuclear factor I-A (NFI-A) to this site. Moreover, for a brain-specific isoform of NFI-A (NFI-A bs), we confirmed the interaction in vivo using chromatin immunoprecipitation (ChIP). Reporter gene assays showed that in neuroblastoma cells, overexpression of NFI-A bs repressed L1 expression threefold.

Conclusion
Our findings suggest that NFI-A, in particular its brain-specific isoform, represses L1 gene expression, and might act as a second silencer of L1 in addition to the neural restrictive silencer factor (NRSF).
Adaptive behavior of neighboring neurons during adaptation-induced plasticity of orientation tuning in V1
Authors: Nemri Abdellatif , Ghisovan Narcis , Shumikhina Svetlana , Molotchnikoff Stéphane 
Published: December 2009

AbstractBackgroundSensory neurons display transient changes of their response properties following prolonged exposure to an appropriate stimulus (adaptation). In adult cat primary visual cortex, orientation-selective neurons shift their preferred orientation after being adapted to a non-preferred orientation. The direction of those shifts, towards (attractive) or away (repulsive) from the adapter depends mostly on adaptation duration. How the adaptive behavior of a neuron is related to that of its neighbors remains unclear.ResultsHere we show that in most cases (75%), cells shift their preferred orientation in the same direction as their neighbors. We also found that cells shifting preferred orientation differently from their neighbors (25%) display three interesting properties: (i) larger variance of absolute shift amplitude, (ii) wider tuning bandwidth and (iii) larger range of preferred orientations among the cluster of cells. Several response properties of V1 neurons depend on their location within the cortical orientation map. Our results suggest that recording sites with both attractive and repulsive shifts following adaptation may be located in close proximity to iso-orientation domain boundaries or pinwheel centers. Indeed, those regions have a more diverse orientation distribution of local inputs that could account for the three properties above. On the other hand, sites with all cells shifting their preferred orientation in the same direction could be located within iso-orientation domains.ConclusionsOur results suggest that the direction and amplitude of orientation preference shifts in V1 depend on location within the orientation map. This anisotropy of adaptation-induced plasticity, comparable to that of the visual cortex itself, could have important implications for our understanding of visual adaptation at the psychophysical level.
Reduced transcription of TCOF1 in adult cells of Treacher Collins syndrome patients
Authors: Masotti Cibele , Ornelas Camila C , Splendore-Gordonos Alessandra , Moura Ricardo , Félix Têmis M , Alonso Nivaldo , Camargo Anamaria A , Passos-Bueno Maria Rita 
Published: December 2009

AbstractBackgroundTreacher Collins syndrome (TCS) is an autosomal dominant craniofacial disorder caused by frameshift deletions or duplications in theTCOF1gene. These mutations cause premature termination codons, which are predicted to lead to mRNA degradation by nonsense mediated mRNA decay (NMD). Haploinsufficiency of the gene product (treacle) during embryonic development is the proposed molecular mechanism underlying TCS. However, it is still unknown ifTCOF1expression levels are decreased in post-embryonic human cells.MethodsWe have estimatedTCOF1transcript levels through real time PCR in mRNA obtained from leucocytes and mesenchymal cells of TCS patients (n = 23) and controls (n = 18). Mutational screening and analysis of NMD were performed by direct sequencing of gDNA and cDNA, respectively.ResultsAll the 23 patients had typical clinical features of the syndrome and pathogenic mutations were detected in 19 of them. We demonstrated that the expression level ofTCOF1is 18-31% lower in patients than in controls (p < 0.05), even if we exclude the patients in whom we did not detect the pathogenic mutation. We also observed that the mutant allele is usually less abundant than the wild type one in mesenchymal cells.ConclusionsThis is the first study to report decreased expression levels ofTCOF1in TCS adult human cells, but it is still unknown if this finding is associated to any phenotype in adulthood. In addition, as we demonstrated that alleles harboring the pathogenic mutations have lower expression, we herein corroborate the current hypothesis of NMD of the mutant transcript as the explanation for diminished levels ofTCOF1expression. Further, considering thatTCOF1deficiency in adult cells could be associated to pathologic clinical findings, it will be important to verify if TCS patients have an impairment in adult stem cell properties, as this can reduce the efficiency of plastic surgery results during rehabilitation of these patients.
Association between polymorphisms in DNA repair genes and survival of non-smoking female patients with lung adenocarcinoma
Authors: Yin Zhihua , Zhou Baosen , He Qincheng , Li Mingchuan , Guan Peng , Li Xuelian , Cui Zeshi , Xue Xiaoxia , Su Meng , Ma Rui , Bai Weijun , Xia Shuyue , Jiang Yanduo , Xu Shun , Lv Yi , Li Xun 
Published: December 2009

Abstract

Background
Excision repair cross-complementing group 1 (ERCC1) and group 2 (ERCC2), and X-ray repair cross-complementing group 1 (XRCC1) proteins play important roles in the repair of DNA damage and adducts. Single nucleotide polymorphisms (SNPs) of DNA repair genes are suspected to influence treatment effect and survival of cancer patients. This study aimed to investigate the relationship between polymorphisms in ERCC2, ERCC1 and XRCC1 genes and survival of non-smoking female patients with lung adenocarcinoma.

Methods
We used polymerase chain reaction-restriction fragment length polymorphism (PCR-RFLP) method to evaluate SNPs in ERCC2, ERCC1 and XRCC1 genes among 257 patients.

Results
The overall median survival time (MST) was 13.07 months. Increasing numbers of either ERCC1 118 or XRCC1 399 variant alleles were associated with shorter survival of non-smoking female lung adenocarcinoma patients (Log-rank P < 0.001). The adjusted hazard ratios (HRs) for individuals with CT or TT genotype at ERCC1 Asn118Asn were 1.48 and 2.67 compared with those with CC genotype. For polymorphism of XRCC1 399, the HRs were 1.28 and 2.68 for GA and AA genotype. When variant alleles across both polymorphisms were combined to analysis, the increasing number of variant alleles was associated with decreasing overall survival. Using the stepwise Cox regression analysis, we found that the polymorphisms in ERCC1 and XRCC1, tumor stage and chemotherapy or radiotherapy status independently predicted overall survival of non-smoking female patients with lung adenocarcinoma.

Conclusions
Genetic polymorphisms in ERCC1 and XRCC1 genes might be prognostic factors in non-smoking female patients with lung adenocarcinoma.
Paediatricians knowledge, attitudes, and practices regarding immunizations for infants in Italy
Authors: Anastasi Daniela , Di Giuseppe Gabriella , Marinelli Paolo , Angelillo Italo F 
Published: December 2009

AbstractBackgroundThe purpose of this study was to investigate whether paediatricians have appropriate knowledge, attitudes, and behaviours regarding vaccinations for infants in Italy.MethodsA random sample of 500 paediatricians received a self-administered anonymous questionnaire covering demographic and professional characteristics; knowledge about the mandatory, recommended, and not indicated vaccinations for infants; attitudes about vaccinations for infants; behaviour regarding current administration or willingness to administer mandatory or recommended vaccinations for infants and immunization education programs of the parents.ResultsOnly 42.3% paediatricians knew all recommended vaccinations for infants and this knowledge was significantly higher in females, in those who worked a higher number of hours for week, and in those who use guidelines for immunization practice. Only 10.3% had a very favourable attitude towards the utility of the recommended vaccinations for infants and this was significantly higher in those who administered recommended vaccinations for infants. A large proportion (82.7%) of paediatricians routinely informed the parents about the recommended vaccinations for infants and this appropriate behaviour was significantly higher among younger, in those with a higher number of years in practice, and in those who administered the recommended vaccinations for infants.ConclusionTraining and educational interventions are needed in order to improve knowledge, attitudes, and behaviours regarding vaccinations for infants among paediatricians.
Characterization of the histone H2A.Z-1 and H2A.Z-2 isoforms in vertebrates
Authors: Dryhurst Deanna , Ishibashi Toyotaka , Rose Kristie L , Eirín-López José M , McDonald Darin , Silva-Moreno Begonia , Veldhoen Nik , Helbing Caren C , Hendzel Michael J , Shabanowitz Jeffrey , Hunt Donald F , Ausió Juan 
Published: December 2009

Abstract

Background

Within chromatin, the histone variant H2A.Z plays a role in many diverse nuclear processes including transcription, preventing the spread of heterochromatin and epigenetic transcriptional memory. The molecular mechanisms of how H2A.Z mediates its effects are not entirely understood. However, it is now known that H2A.Z has two protein isoforms in vertebrates, H2A.Z-1 and H2A.Z-2, which are encoded by separate genes and differ by 3 amino acid residues.

Results

We report that H2A.Z-1 and H2A.Z-2 are expressed across a wide range of human tissues, they are both acetylated at lysine residues within the N-terminal region and they exhibit similar, but nonidentical, distributions within chromatin. Our results suggest that H2A.Z-2 preferentially associates with H3 trimethylated at lysine 4 compared to H2A.Z-1. The phylogenetic analysis of the promoter regions of H2A.Z-1 and H2A.Z-2 indicate that they have evolved separately during vertebrate evolution.

Conclusions

Our biochemical, gene expression, and phylogenetic data suggest that the H2A.Z-1 and H2A.Z-2 variants function similarly yet they may have acquired a degree of functional independence.
Peripheral Non-Viral MIDGE Vector-Driven Delivery of β-Endorphin in Inflammatory Pain
Authors: Machelska Halina , Schroff Matthias , Oswald Detlef , Binder Waltraud , Sitte Nicolle , Mousa Shaaban A , Rittner Heike L , Brack Alexander , Labuz Dominika , Busch Melanie , Wittig Burghardt , Schäfer Michael , Stein Christoph 
Published: December 2009

Background Leukocytes infiltrating inflamed tissue produce and release opioid peptides such as β-endorphin, which activate opioid receptors on peripheral terminals of sensory nerves resulting in analgesia. Gene therapy is an attractive strategy to enhance continuous production of endogenous opioids. However, classical viral and plasmid vectors for gene delivery are hampered by immunogenicity, recombination, oncogene activation, antibacterial antibody production or changes in physiological gene expression. Non-viral, non-plasmid minimalistic, immunologically defined gene expression (MIDGE) vectors may overcome these problems as they carry only elements needed for gene transfer. Here, we investigated the effects of a nuclear localization sequence (NLS)-coupled MIDGE encoding the β-endorphin precursor proopiomelanocortin (POMC) on complete Freund's adjuvant-induced inflammatory pain in rats. Results POMC-MIDGE-NLS injected into inflamed paws appeared to be taken up by leukocytes resulting in higher concentrations of β-endorphin in these cells. POMC-MIDGE-NLS treatment reversed enhanced mechanical sensitivity compared with control MIDGE-NLS. However, both effects were moderate, not always statistically significant or directly correlated with each other. Also, the anti-hyperalgesic actions could not be increased by enhancing β-endorphin secretion or by modifying POMC-MIDGE-NLS to code for multiple copies of β-endorphin. Conclusion Although MIDGE vectors circumvent side-effects associated with classical viral and plasmid vectors, the current POMC-MIDGE-NLS did not result in reliable analgesic effectiveness in our pain model. This was possibly associated with insufficient and variable efficacy in transfection and/or β-endorphin production. Our data point at the importance of the reproducibility of gene therapy strategies for the control of chronic pain.
No difference in between-country variability in use of newly approved orphan and non- orphan medicinal products - a pilot study
Authors: Stolk Pieter , Heemstra Harald E , Leufkens Hubert GM , Bloechl-Daum Brigitte , Heerdink Eibert R 
Published: December 2009

Abstract

Background
Regulators and payers have to strike a balance between the needs of the patient and the optimal allocation of resources. Drugs indicated for rare diseases (orphan medicines) are a special group in this context because of their often high per unit costs. Our objective in this pilot study was to determine, for drugs used in an outpatient setting, how utilisation of centrally authorised drugs varies between countries across a selection of EU member states.

Methods
We randomly selected five orphan medicines and nine other drugs that were centrally authorised in the European Union between January 2000 and November 2006. We compared utilisation of these drugs in six European Union member states: Austria, Denmark, Finland, Portugal, The Netherlands, and Sweden. Utilisation data were expressed as Defined Daily Doses per 1000 persons per year. Variability in use across countries was determined by calculating the relative standard deviation for the utilisation rates of individual drugs across countries.

Results
No association between orphan medicine status and variability in use across countries was found (P = 0.52). Drugs with an orphan medicine status were more expensive and had a higher innovation score than drugs without an orphan medicine status.

Conclusions
The results show that the variability in use of orphan medicines in the different health care systems of the European Union appears to be comparable to the other newly authorised drugs that were included in the analysis. This means that, although strong heterogeneity in access may exist, this heterogeneity is not specific for drugs with an orphan status.