bluuebunny/crossref_metadata_2025_split huggingface dataset:
A compatible exon-exon junction database for the identification of exon skipping events using tandem mass spectrum data
Authors: Mo Fan , Hong Xu , Gao Feng , Du Lin , Wang Jun , Omenn Gilbert S , Lin Biaoyang 
Published: December 2008

Abstract

Background
Alternative splicing is an important gene regulation mechanism. It is estimated that about 74% of multi-exon human genes have alternative splicing. High throughput tandem (MS/MS) mass spectrometry provides valuable information for rapidly identifying potentially novel alternatively-spliced protein products from experimental datasets. However, the ability to identify alternative splicing events through tandem mass spectrometry depends on the database against which the spectra are searched.

Results
We wrote scripts in perl, Bioperl, mysql and Ensembl API and built a theoretical exon-exon junction protein database to account for all possible combinations of exons for a gene while keeping the frame of translation (i.e., keeping only in-phase exon-exon combinations) from the Ensembl Core Database. Using our liver cancer MS/MS dataset, we identified a total of 488 non-redundant peptides that represent putative exon skipping events.

Conclusion
Our exon-exon junction database provides the scientific community with an efficient means to identify novel alternatively spliced (exon skipping) protein isoforms using mass spectrometry data. This database will be useful in annotating genome structures using rapidly accumulating proteomics data.
Enhanced Bayesian modelling in BAPS software for learning genetic structures of populations
Authors: Corander Jukka , Marttinen Pekka , Sirén Jukka , Tang Jing 
Published: December 2008

AbstractBackgroundDuring the most recent decade many Bayesian statistical models and software for answering questions related to the genetic structure underlying population samples have appeared in the scientific literature. Most of these methods utilize molecular markers for the inferences, while some are also capable of handling DNA sequence data. In a number of earlier works, we have introduced an array of statistical methods for population genetic inference that are implemented in the software BAPS. However, the complexity of biological problems related to genetic structure analysis keeps increasing such that in many cases the current methods may provide either inappropriate or insufficient solutions.ResultsWe discuss the necessity of enhancing the statistical approaches to face the challenges posed by the ever-increasing amounts of molecular data generated by scientists over a wide range of research areas and introduce an array of new statistical tools implemented in the most recent version of BAPS. With these methods it is possible, e.g., to fit genetic mixture models using user-specified numbers of clusters and to estimate levels of admixture under a genetic linkage model. Also, alleles representing a different ancestry compared to the average observed genomic positions can be tracked for the sampled individuals, anda priorispecified hypotheses about genetic population structure can be directly compared using Bayes' theorem. In general, we have improved further the computational characteristics of the algorithms behind the methods implemented in BAPS facilitating the analyses of large and complex datasets. In particular, analysis of a single dataset can now be spread over multiple computers using a script interface to the software.ConclusionThe Bayesian modelling methods introduced in this article represent an array of enhanced tools for learning the genetic structure of populations. Their implementations in the BAPS software are designed to meet the increasing need for analyzing large-scale population genetics data. The software is freely downloadable for Windows, Linux and Mac OS X systems athttp://web.abo.fi/fak/mnf//mate/jc/software/baps.html.
Shape-IT: new rapid and accurate algorithm for haplotype inference
Authors: Delaneau Olivier , Coulonges Cédric , Zagury Jean-François 
Published: December 2008

AbstractBackgroundWe have developed a new computational algorithm, Shape-IT, to infer haplotypes under the genetic model of coalescence with recombination developed by Stephens et al in Phase v2.1. It runs much faster than Phase v2.1 while exhibiting the same accuracy. The major algorithmic improvements rely on the use of binary trees to represent the sets of candidate haplotypes for each individual. These binary tree representations: (1) speed up the computations of posterior probabilities of the haplotypes by avoiding the redundant operations made in Phase v2.1, and (2) overcome the exponential aspect of the haplotypes inference problem by the smart exploration of the most plausible pathways (ie. haplotypes) in the binary trees.ResultsOur results show that Shape-IT is several orders of magnitude faster than Phase v2.1 while being as accurate. For instance, Shape-IT runs 50 times faster than Phase v2.1 to compute the haplotypes of 200 subjects on 6,000 segments of 50 SNPs extracted from a standard Illumina 300 K chip (13 days instead of 630 days). We also compared Shape-IT with other widely used software, Gerbil, PL-EM, Fastphase, 2SNP, and Ishape in various tests: Shape-IT and Phase v2.1 were the most accurate in all cases, followed by Ishape and Fastphase. As a matter of speed, Shape-IT was faster than Ishape and Fastphase for datasets smaller than 100 SNPs, but Fastphase became faster -but still less accurate- to infer haplotypes on larger SNP datasets.ConclusionShape-IT deserves to be extensively used for regular haplotype inference but also in the context of the new high-throughput genotyping chips since it permits to fit the genetic model of Phase v2.1 on large datasets. This new algorithm based on tree representations could be used in other HMM-based haplotype inference software and may apply more largely to other fields using HMM.
Patterning of palatal rugae through sequential addition reveals an anterior/posterior boundary in palatal development
Authors: Pantalacci Sophie , Prochazka Jan , Martin Arnaud , Rothova Michaela , Lambert Anne , Bernard Laure , Charles Cyril , Viriot Laurent , Peterkova Renata , Laudet Vincent 
Published: December 2008

Abstract
Background
The development of the secondary palate has been a main topic in craniofacial research, as its failure results in cleft palate, one of the most common birth defects in human. Nevertheless, palatal rugae (or rugae palatinae), which are transversal ridges developing on the secondary palate, received little attention. However, rugae could be useful as landmarks to monitor anterior/posterior (A/P) palatal growth, and they provide a simple model of mesenchymal-epithelial structures arranged in a serial pattern.

Results
We first determined in which order the nine mouse rugae appear during development. Our results revealed a reiterative process, which is coupled with A/P growth of palatal shelves, and by which rugae 3 to 7b are sequentially interposed, in the increasing distance between the second most anterior ruga, ruga 2, and the two most posterior rugae, rugae 8 and 9. We characterized the steps of ruga interposition in detail, showing that a new ruga forms from an active zone of high proliferation rate, next to the last formed ruga. Then, by analyzing the polymorphism of wild type and EdaTa mutant mice, we suggest that activation-inhibition mechanisms may be involved in positioning new rugae, like for other skin appendages. Finally, we show that the ruga in front of which new rugae form, i.e. ruga 8 in mouse, coincides with an A/P gene expression boundary in the palatal shelves (Shox2/Meox2-Tbx22). This coincidence is significant, since we also found it in hamster, despite differences in the adult ruga pattern of these two species.

Conclusion
We showed that palatal rugae are sequentially added to the growing palate, in an interposition process that appears to be dependent on activation-inhibition mechanisms and reveals a new developmental boundary in the growing palate. Further studies on rugae may help to shed light on both the development and evolution of structures arranged in regular patterns. Moreover, rugae will undoubtedly be powerful tools to further study the anteroposterior regionalization of the growing palate.
Combinatorial control of gene expression by the three yeast repressors Mig1, Mig2 and Mig3
Authors: Westholm Jakub Orzechowski , Nordberg Niklas , Murén Eva , Ameur Adam , Komorowski Jan , Ronne Hans 
Published: December 2008

AbstractBackgroundExpression of a large number of yeast genes is repressed by glucose. The zinc finger protein Mig1 is the main effector in glucose repression, but yeast also has two related proteins: Mig2 and Mig3. We have used microarrays to study global gene expression in all possible combinations ofmig1,mig2andmig3deletion mutants.ResultsMig1 and Mig2 repress a largely overlapping set of genes on 2% glucose. Genes that are upregulated in amig1 mig2double mutant were grouped according to the contribution of Mig2. Most of them show partially redundant repression, with Mig1 being the major repressor, but some genes show complete redundancy, and some are repressed only by Mig1. Several redundantly repressed genes are involved in phosphate metabolism. The promoters of these genes are enriched for Pho4 sites, a novel GGGAGG motif, and a variant Mig1 site which is absent from genes repressed only by Mig1. Genes repressed only by Mig1 on 2% glucose include the hexose transporter geneHXT4, but Mig2 contributes toHXT4repression on 10% glucose.HXT6is one of the few genes that are more strongly repressed by Mig2. Mig3 does not seem to overlap in function with Mig1 and Mig2. Instead, Mig3 downregulates theSIR2gene encoding a histone deacetylase involved in gene silencing and the control of aging.ConclusionMig2 fine-tunes glucose repression by targeting a subset of the Mig1-repressed genes, and by responding to higher glucose concentrations. Mig3 does not target the same genes as Mig1 and Mig2, but instead downregulates theSIR2gene.
High quality draft sequences for prokaryotic genomes using a mix of new sequencing technologies
Authors: Aury Jean-Marc , Cruaud Corinne , Barbe Valérie , Rogier Odile , Mangenot Sophie , Samson Gaelle , Poulain Julie , Anthouard Véronique , Scarpelli Claude , Artiguenave François , Wincker Patrick 
Published: December 2008

Abstract

Background
Massively parallel DNA sequencing instruments are enabling the decoding of whole genomes at significantly lower cost and higher throughput than classical Sanger technology. Each of these technologies have been estimated to yield assemblies with more problematic features than the standard method. These problems are of a different nature depending on the techniques used. So, an appropriate mix of technologies may help resolve most difficulties, and eventually provide assemblies of high quality without requiring any Sanger-based input.

Results
We compared assemblies obtained using Sanger data with those from different inputs from New Sequencing Technologies. The assemblies were systematically compared with a reference finished sequence. We found that the 454 GSFLX can efficiently produce high continuity when used at high coverage. The potential to enhance continuity by scaffolding was tested using 454 sequences from circularized genomic fragments. Finally, we explore the use of Solexa-Illumina short reads to polish the genome draft by implementing a technique to correct 454 consensus errors.

Conclusion
High quality drafts can be produced for small genomes without any Sanger data input. We found that 454 GSFLX and Solexa/Illumina show great complementarity in producing large contigs and supercontigs with a low error rate.
Investigation of Gamma-aminobutyric acid (GABA) A receptors genes and migraine susceptibility
Authors: Fernandez Francesca , Esposito Teresa , Lea Rod A , Colson Natalie J , Ciccodicola Alfredo , Gianfrancesco Fernando , Griffiths Lyn R 
Published: December 2008

AbstractBackgroundMigraine is a neurological disorder characterized by recurrent attacks of severe headache, affecting around 12% of Caucasian populations. It is well known that migraine has a strong genetic component, although the number and type of genes involved is still unclear. Prior linkage studies have reported mapping of a migraine gene to chromosome Xq 24–28, a region containing a cluster of genes for GABA A receptors (GABRE, GABRA3, GABRQ), which are potential candidate genes for migraine. The GABA neurotransmitter has been implicated in migraine pathophysiology previously; however its exact role has not yet been established, although GABA receptors agonists have been the target of therapeutic developments. The aim of the present research is to investigate the role of the potential candidate genes reported on chromosome Xq 24–28 region in migraine susceptibility. In this study, we have focused on the subunit GABA A receptors type ε (GABRE) and type θ (GABRQ) genes and their involvement in migraine.MethodsWe have performed an association analysis in a large population of case-controls (275 unrelated Caucasian migraineurs versus 275 controls) examining a set of 3 single nucleotide polymorphisms (SNPs) in the coding region (exons 3, 5 and 9) of the GABRE gene and also the I478F coding variant of the GABRQ gene.ResultsOur study did not show any association between the examined SNPs in our test population (P > 0.05).ConclusionAlthough these particular GABA receptor genes did not show positive association, further studies are necessary to consider the role of other GABA receptor genes in migraine susceptibility.
Immunological tolerance and tumor rejection in embryo-aggregated chimeric mice – Lessons for tumor immunity
Authors: Wagner Alexander Y , Holle Eric , Holle Lori , Yu Xianzhong , Schwamberger Günter 
Published: December 2008

Abstract

Background
Rejection of transplanted tumors by the immune system is a rare event in syngeneic hosts, and is considered to be dependent on the local interaction of defensive immune reactions and tumor tolerance mechanisms. Here, we have enlisted the aid of a unique set of embryo-aggregated lineage chimeric mice derived from C57/BL6 and FVB donors to study the interplay between local and systemic tumor immunity and tolerance in rejection of mouse B16 melanoma cells, syngeneic to the C57/BL6 donor strain.

Methods
Two variants of embryo-aggregated chimeric mice with either variable or no contribution of C57-derived cells to their skin were generated by the fusion of different ratios of morula stage blastomers. Chimeric mice were analyzed for s.c. growth of B16 tumors in comparison to their respective donor strains as well as normal F1 hybrids, and the relative frequencies of cellular components of the immune system by FACS analysis of peripheral blood or lymph node cells.

Results
B16 tumors grew significantly faster in mice with full chimerism in their skin as compared to syngeneic C57 or semi-syngeneic C57 × FVB F1 hosts. In contrast, s.c. tumor growth was either absent or significantly reduced in chimeric mice lacking C57-derived cells in their skin, but tolerant to C57 tissue in other organs. Comparison of the relative frequencies of various immune cells in the periphery via FACS-analysis did not reveal any significant differences between the two types of chimeric mice with respect to their donor strains.

Conclusion
Our data suggest a complex interplay between mechanisms of local peripheral tolerance and innate antitumor mechanisms possibly involving NK cell allorecognition as a basis for the differential growth or rejection of B16 tumors in these unique chimeric mice, which we suggest to constitute a valuable new model system for the study of immune-mediated tumor rejection.
Gene expression deregulation by KRAS G12D and G12V in a BRAF V600E context
Authors: Monticone Massimiliano , Biollo Emanuela , Maffei Massimo , Donadini Alessandra , Romeo Francesco , Storlazzi Clelia Tiziana , Giaretti Walter , Castagnola Patrizio 
Published: December 2008

Abstract

Background

KRAS and BRAF mutations appear of relevance in the genesis and progression of several solid tumor types but the co-occurrence and interaction of these mutations have not yet been fully elucidated. Using a microsatellite stable (MSS) colorectal cancer (CRC) cell line (Colo741) having mutated BRAF and KRAS

WT
, we also aimed to investigate the KRAS-BRAF interaction. Gene expression profiles for control KRAS

WT
, KRAS

G 12V
and KRAS

G 12D
transfected cells were obtained after cell clone selection and RT-PCR screening. Extensive qPCR was performed to confirm microarray data.

Results
We found that the KRAS

G 12V
state deregulated several genes associated to cell cycle, apoptosis and nitrogen metabolism. These findings indicated a reduced survival and proliferation with respect to the KRAS

WT
state. The KRAS

G 12D
state was, instead, characterized by several other distinct functional changes as for example those related to chromatin organization and cell-cell adhesion without affecting apoptosis related genes.

Conclusion
These data predict that the G12D mutation may be more likely selected in a BRAF mutated context. At the same time, the presence of the KRAS

G 12V
mutation in the cells escaping apoptosis and inducing angiogenesis via IL8 may confer a more aggressive phenotype. The present results get along with the observations that CRCs with G12V are associated with a worse prognosis with respect to the WT and G12D states and may help identifying novel CRC pathways and biomarkers of clinical relevance.
The impact of close surveillance on pregnancy outcome among women with a prior history of antepartum complications attributed to thrombosis: a cohort study
Authors: Salim Raed , Czarnowicki Tali , Nachum Zohar , Shalev Eliezer 
Published: December 2008

Abstract

Background
There is limited evidence, so far, as to the optimal management of women with a prior obstetric history of antepartum complications attributed to thrombosis. We aimed to investigate the contribution of close antepartum surveillance on pregnancy outcome among women with prior antepartum complications attributed to thrombosis.

Methods
The study was conducted on all women who were delivered, conceived and delivered again between January 2000 and January 2006 at a university teaching hospital. Women included were managed in previous pregnancy at a low risk setting and had unpredicted antepartum complications occurring at a gestational age of 23 weeks or more. Antepartum complications considered were intrauterine fetal death, neonates who were small for gestational age, severe pre-eclampsia and placental abruption. All women were tested for the presence of thrombophilia after delivery. In the following pregnancy, only women found to have any thrombophilia (thrombophilic group) were treated with enoxaparin. Both the thrombophilic group and the non-thrombophilic group (tested negatively for thrombophilia) were managed and observed closely at our high-risk pregnancy clinic.

Results
Ninety-seven women, who conceived at least once after the diagnosis of the relevant antepartum complications, were included in this study. Forty-nine had any thrombophilia and 48 tested negatively. Composite antepartum complications (all antepartum complications considered) were reduced significantly after close antepartum surveillance in both groups. Mean birth weight and mean gestational age improved significantly and were comparable between the groups.

Conclusion
Close antepartum surveillance may contribute to improvement in the perinatal outcomes of women with prior antepartum complications attributed to thrombosis.
Regulation of P450 oxidoreductase by gonadotropins in rat ovary and its effect on estrogen production
Authors: Inaoka Yoshihiko , Yazawa Takashi , Mizutani Tetsuya , Kokame Koichi , Kangawa Kenji , Uesaka Miki , Umezawa Akihiro , Miyamoto Kaoru 
Published: December 2008

Abstract

Background
P450 oxidoreductase (POR) catalyzes electron transfer to microsomal P450 enzymes. Its deficiency causes Antley-Bixler syndrome (ABS), and about half the patients with ABS have ambiguous genitalia and/or impaired steroidogenesis. POR mRNA expression is up-regulated when mesenchymal stem cells (MSCs) differentiate into steroidogenic cells, suggesting that the regulation of POR gene expression is important for steroidogenesis. In this context we examined the regulation of POR expression in ovarian granulosa cells by gonadotropins, and its possible role in steroidogenesis.

Methods
Changes in gene expression in MSCs during differentiation into steroidogenic cells were examined by DNA microarray analysis. Changes in mRNA and protein expression of POR in the rat ovary or in granulosa cells induced by gonadotropin treatment were examined by reverse transcription-polymerase chain reaction and western blotting. Effects of transient expression of wild-type or mutant (R457H or V492E) POR proteins on the production of estrone in COS-7 cells were examined in vitro. Effects of POR knockdown were also examined in estrogen producing cell-line, KGN cells.

Results
POR mRNA was induced in MSCs following transduction with the SF-1 retrovirus, and was further increased by cAMP treatment. Expression of POR mRNA, as well as Cyp19 mRNA, in the rat ovary were induced by equine chorionic gonadotropin and human chorionic gonadotropin. POR mRNA and protein were also induced by follicle stimulating hormone in primary cultured rat granulosa cells, and the induction pattern was similar to that for aromatase. Transient expression of POR in COS-7 cells, which expressed a constant amount of aromatase protein, greatly increased the rate of conversion of androstenedione to estrone, in a dose-dependent manner. The expression of mutant POR proteins (R457H or V492E), such as those found in ABS patients, had much less effect on aromatase activity than expression of wild-type POR proteins. Knockdown of endogenous POR protein in KGN human granulosa cells led to reduced estrone production, indicating that endogenous POR affected aromatase activity.

Conclusion
We demonstrated that the expression of POR, together with that of aromatase, was regulated by gonadotropins, and that its induction could up-regulate aromatase activity in the ovary, resulting in a coordinated increase in estrogen production.