bluuebunny/crossref_metadata_2025 huggingface dataset:
Initial steps towards a production platform for DNA sequence analysis on the grid
Authors: Luyf Angela CM , van Schaik Barbera DC , de Vries Michel , Baas Frank , van Kampen Antoine HC , Olabarriaga Silvia D
Published: January 2011

Background

Bioinformatics is confronted with a new data explosion due to the availability of high throughput DNA sequencers. Data storage and analysis becomes a problem on local servers, and therefore it is needed to switch to other IT infrastructures. Grid and workflow technology can help to handle the data more efficiently, as well as facilitate collaborations. However, interfaces to grids are often unfriendly to novice users.

Results

In this study we reused a platform that was developed in the VL-e project for the analysis of medical images. Data transfer, workflow execution and job monitoring are operated from one graphical interface. We developed workflows for two sequence alignment tools (BLAST and BLAT) as a proof of concept. The analysis time was significantly reduced. All workflows and executables are available for the members of the Dutch Life Science Grid and the VL-e Medical virtual organizations All components are open source and can be transported to other grid infrastructures.

Conclusions

The availability of in-house expertise and tools facilitates the usage of grid resources by new users. Our first results indicate that this is a practical, powerful and scalable solution to address the capacity and collaboration issues raised by the deployment of next generation sequencers. We currently adopt this methodology on a daily basis for DNA sequencing and other applications. More information and source code is available viahttp://www.bioinformaticslaboratory.nl/
Content-based microarray search using differential expression profiles
Authors: Engreitz Jesse M , Morgan Alexander A , Dudley Joel T , Chen Rong , Thathoo Rahul , Altman Russ B , Butte Atul J
Published: January 2011

Background

With the expansion of public repositories such as the Gene Expression Omnibus (GEO), we are rapidly cataloging cellular transcriptional responses to diverse experimental conditions. Methods that query these repositories based on gene expression content, rather than textual annotations, may enable more effective experiment retrieval as well as the discovery of novel associations between drugs, diseases, and other perturbations.

Results

We develop methods to retrieve gene expression experiments that differentially express the same transcriptional programs as a query experiment. Avoiding thresholds, we generate differential expression profiles that include a score for each gene measured in an experiment. We use existing and novel dimension reduction and correlation measures to rank relevant experiments in an entirely data-driven manner, allowing emergent features of the data to drive the results. A combination of matrix decomposition andp-weighted Pearson correlation proves the most suitable for comparing differential expression profiles. We apply this method to index all GEO DataSets, and demonstrate the utility of our approach by identifying pathways and conditions relevant to transcription factors Nanog and FoxO3.

Conclusions

Content-based gene expression search generates relevant hypotheses for biological inquiry. Experiments across platforms, tissue types, and protocols inform the analysis of new datasets.
CNV-WebStore: Online CNV Analysis, Storage and Interpretation
Authors: Vandeweyer Geert , Reyniers Edwin , Wuyts Wim , Rooms Liesbeth , Kooy R Frank
Published: January 2011

Background

Microarray technology allows the analysis of genomic aberrations at an ever increasing resolution, making functional interpretation of these vast amounts of data the main bottleneck in routine implementation of high resolution array platforms, and emphasising the need for a centralised and easy to use CNV data management and interpretation system.

Results

We present CNV-WebStore, an online platform to streamline the processing and downstream interpretation of microarray data in a clinical context, tailored towards but not limited to the Illumina BeadArray platform. Provided analysis tools include CNV analsyis, parent of origin and uniparental disomy detection. Interpretation tools include data visualisation, gene prioritisation, automated PubMed searching, linking data to several genome browsers and annotation of CNVs based on several public databases. Finally a module is provided for uniform reporting of results.

Conclusion

CNV-WebStore is able to present copy number data in an intuitive way to both lab technicians and clinicians, making it a useful tool in daily clinical practice.
Ligands specify estrogen receptor alpha nuclear localization and degradation
Authors: Kocanova Silvia , Mazaheri Mahta , Caze-Subra Stéphanie , Bystricky Kerstin
Published: January 2011

Background

The estrogen receptor alpha (ERα) is found predominately in the nucleus, both in hormone stimulated and untreated cells. Intracellular distribution of the ERα changes in the presence of agonists but the impact of different antiestrogens on the fate of ERα is a matter of debate.

Results

A MCF-7 cell line stably expressing GFP-tagged human ERα (SK19 cell line) was created to examine the localization of ligand-bound GFP-ERα. We combined digitonin-based cell fractionation analyses with fluorescence and immuno-electron microscopy to determine the intracellular distribution of ligand-bound ERα and/or GFP-ERα.

Using fluorescence- and electron microscopy we demonstrate that both endogenous ERα and GFP-ERα form numerous nuclear focal accumulations upon addition of agonist, 17β-estradiol (E2), and pure antagonists (selective estrogen regulator disruptor; SERD), ICI 182,780 or RU58,668, while in the presence of partial antagonists (selective estrogen regulator modulator; SERM), 4-hydroxytamoxifen (OHT) or RU39,411, diffuse nuclear staining persisted.

Digitonin based cell fractionation analyses confirmed that endogenous ERα and GFP-ERα predominantly reside in the nuclear fraction. Overall ERα protein levels were reduced after estradiol treatment. In the presence of SERMs ERα was stabilized in the nuclear soluble fraction, while in the presence of SERDs protein levels decreased drastically and the remaining ERα was largely found in a nuclear insoluble fraction. mRNA levels ofESR1were reduced compared to untreated cells in the presence of all ligands tested, including E2. E2 and SERDs induced ERα degradation occurred in distinct nuclear foci composed of ERα and the proteasome providing a simple explanation for ERα sequestration in the nucleus.

Conclusions

Our results indicate that chemical structure of ligands directly affect the nuclear fate and protein turnover of the estrogen receptor alpha independently of their impact on transcription. These findings provide a molecular basis for the selection of antiestrogen compounds issue from pharmacological studies aimed at improving treatment of breast cancer.
Molecular dissection of the migrating posterior lateral line primordium during early development in zebrafish
Authors: Gallardo Viviana E , Liang Jin , Behra Martine , Elkahloun Abdel , Villablanca Eduardo J , Russo Vincenzo , Allende Miguel L , Burgess Shawn M
Published: January 2011

Background

Development of the posterior lateral line (PLL) system in zebrafish involves cell migration, proliferation and differentiation of mechanosensory cells. The PLL forms when cranial placodal cells delaminate and become a coherent, migratory primordium that traverses the length of the fish to form this sensory system. As it migrates, the primordium deposits groups of cells called neuromasts, the specialized organs that contain the mechanosensory hair cells. Therefore the primordium provides both a model for studying collective directional cell migration and the differentiation of sensory cells from multipotent progenitor cells.

Results

Through the combined use of transgenic fish, Fluorescence Activated Cell Sorting and microarray analysis we identified a repertoire of key genes expressed in the migrating primordium and in differentiated neuromasts. We validated the specific expression in the primordium of a subset of the identified sequences by quantitative RT-PCR, and byin situhybridization. We also show that interfering with the function of two genes,f11randcd9b, defects in primordium migration are induced. Finally, pathway construction revealed functional relationships among the genes enriched in the migrating cell population.

Conclusions

Our results demonstrate that this is a robust approach to globally analyze tissue-specific expression and we predict that many of the genes identified in this study will show critical functions in developmental events involving collective cell migration and possibly in pathological situations such as tumor metastasis.
Next generation sequencing and analysis of a conserved transcriptome of New Zealand's kiwi
Authors: Subramanian Sankar , Huynen Leon , Millar Craig D , Lambert David M
Published: January 2011

Background

Kiwi is a highly distinctive, flightless and endangered ratite bird endemic to New Zealand. To understand the patterns of molecular evolution of the nuclear protein-coding genes in brown kiwi (Apteryx australis mantelli) and to determine the timescale of avian history we sequenced a transcriptome obtained from a kiwi embryo using next generation sequencing methods. We then assembled the conserved protein-coding regions using the chicken proteome as a scaffold.

Results

Using 1,543 conserved protein coding genes we estimated the neutral evolutionary divergence between the kiwi and chicken to be ~45%, which is approximately equal to the divergence computed for the human-mouse pair using the same set of genes. A large fraction of genes was found to be under high selective constraint, as most of the expressed genes appeared to be involved in developmental gene regulation. Our study suggests a significant relationship between gene expression levels and protein evolution. Using sequences from over 700 nuclear genes we estimated the divergence between the two basal avian groups, Palaeognathae and Neognathae to be 132 million years, which is consistent with previous studies using mitochondrial genes.

Conclusions

The results of this investigation revealed patterns of mutation and purifying selection in conserved protein coding regions in birds. Furthermore this study suggests a relatively cost-effective way of obtaining a glimpse into the fundamental molecular evolutionary attributes of a genome, particularly when no closely related genomic sequence is available.
The relationship between the error catastrophe, survival of the flattest, and natural selection
Authors: Tejero Héctor , Marín Arturo , Montero Francisco
Published: January 2011

Background

The quasispecies model is a general model of evolution that is generally applicable to replication up to high mutation rates. It predicts that at a sufficiently high mutation rate, quasispecies with higher mutational robustness can displace quasispecies with higher replicative capacity, a phenomenon called "survival of the flattest". In some fitness landscapes it also predicts the existence of a maximum mutation rate, called the error threshold, beyond which the quasispecies enters into error catastrophe, losing its genetic information. The aim of this paper is to study the relationship between survival of the flattest and the transition to error catastrophe, as well as the connection between these concepts and natural selection.

Results

By means of a very simplified model, we show that the transition to an error catastrophe corresponds to a value of zero for the selective coefficient of the mutant phenotype with respect to the master phenotype, indicating that transition to the error catastrophe is in this case similar to the selection of a more robust species. This correspondence has been confirmed by considering a single-peak landscape in which sequences are grouped with respect to their Hamming distant from the master sequence. When the robustness of a classe is changed by modification of its quality factor, the distribution of the population changes in accordance with the new value of the robustness, although an error catastrophe can be detected at the same values as in the general case. When two quasispecies of different robustness competes with one another, the entry of one of them into error catastrophe causes displacement of the other, because of the greater robustness of the former. Previous works are explicitly reinterpreted in the light of the results obtained in this paper.

Conclusions

The main conclusion of this paper is that the entry into error catastrophe is a specific case of survival of the flattest acting on phenotypes that differ in the trade-off between replicative ability and mutational robustness. In fact, entry into error catastrophe occurs when the mutant phenotype acquires a selective advantage over the master phenotype. As both entry into error catastrophe and survival of the flattest are caused by natural selection when mutation rate is increased, we propose differentiating between them by the level of selection at which natural selection acts. So we propose to consider the transition to error catastrophe as a phenomenon of intra-quasispecies selection, and survival of the flattest as a phenomenon of inter-quasispecies selection.
Regulatory polymorphisms in the bovine Ankyrin 1 gene promoter are associated with tenderness and intramuscular fat content
Authors: Aslan Ozlem , Sweeney Torres , Mullen Anne Maria , Hamill Ruth M
Published: January 2011

Background

Recent QTL and gene expression studies have highlighted ankyrins as positional and functional candidate genes for meat quality. Our objective was to characterise the promoter region of the bovine ankyrin 1 gene and to test polymorphisms for association with sensory and technological meat quality measures.

Results

Seven novel promoter SNPs were identified in a 1.11 kb region of the ankyrin 1 promoter in Angus, Charolais and Limousin bulls (n = 15 per breed) as well as 141 crossbred beef animals for which meat quality data was available. Eighteen haplotypes were inferred with significant breed variation in haplotype frequencies. The five most frequent SNPs and the four most frequent haplotypes were subsequently tested for association with sensory and technological measures of meat quality in the crossbred population. SNP1, SNP3 and SNP4 (which were subsequently designated regulatory SNPs) and SNP5 were associated with traits that contribute to sensorial and technological measurements of tenderness and texture; Haplotype 1 and haplotype 4 were oppositely correlated with traits contributing to tenderness (P < 0.05). While no single SNP was associated with intramuscular fat (IMF), a clear association with increased IMF and juiciness was observed for haplotype 2.

Conclusion

The conclusion from this study is that alleles defining haplotypes 2 and 4 could usefully contribute to marker SNP panels used to select individuals with improved IMF/juiciness or tenderness in a genome-assisted selection framework.
Recent transfer of an iron-regulated gene from the plastid to the nuclear genome in an oceanic diatom adapted to chronic iron limitation
Authors: Lommer Markus , Roy Alexandra-Sophie , Schilhabel Markus , Schreiber Stefan , Rosenstiel Philip , LaRoche Julie
Published: January 2011

Background

Although the importance and widespread occurrence of iron limitation in the contemporary ocean is well documented, we still know relatively little about genetic adaptation of phytoplankton to these environments. Compared to its coastal relativeThalassiosira pseudonana, the oceanic diatomThalassiosira oceanicais highly tolerant to iron limitation. The adaptation to low-iron conditions inT. oceanicahas been attributed to a decrease in the photosynthetic components that are rich in iron. Genomic information onT. oceanicamay shed light on the genetic basis of the physiological differences between the two species.

Results

The complete 141790 bp sequence of theT. oceanicachloroplast genome [GenBank: GU323224], assembled from massively parallel pyrosequencing (454) shotgun reads, revealed that thepetFgene encoding for ferredoxin, which is localized in the chloroplast genome inT. pseudonanaand other diatoms, has been transferred to the nucleus inT. oceanica. The iron-sulfur protein ferredoxin, a key element of the chloroplast electron transport chain, can be replaced by the iron-free flavodoxin under iron-limited growth conditions thereby contributing to a reduction in the cellular iron requirements. From a comparison to the genomic context of theT. pseudonana petFgene, theT. oceanicaortholog can be traced back to its chloroplast origin. The coding potential of theT. oceanicachloroplast genome is comparable to that ofT. pseudonanaandPhaeodactylum tricornutum, though a novel expressed ORF appears in the genomic region that has been subjected to rearrangements linked to thepetFgene transfer event.

Conclusions

The transfer of thepetFfrom the cp to the nuclear genome inT. oceanicarepresents a major difference between the two closely related species. The ability ofT. oceanicato tolerate iron limitation suggests that the transfer ofpetFfrom the chloroplast to the nuclear genome might have contributed to the ecological success of this species.
The vertebrate makorin ubiquitin ligase gene family has been shaped by large-scale duplication and retroposition from an ancestral gonad-specific, maternal-effect gene
Authors: Böhne Astrid , Darras Amandine , D'Cotta Helena , Baroiller Jean-Francois , Galiana-Arnoux Delphine , Volff Jean-Nicolas
Published: January 2011

Background

Members of the makorin(mkrn)gene family encode RING/C3H zinc finger proteins with U3 ubiquitin ligase activity. Although these proteins have been described in a variety of eukaryotes such as plants, fungi, invertebrates and vertebrates including human, almost nothing is known about their structural and functional evolution.

Results

Via partial sequencing of a testis cDNA library from the poeciliid fishXiphophorus maculatus, we have identified a new member of themakoringene family, that we calledmkrn4. In addition to the already describedmkrn1andmkrn2,mkrn4is the third example of a makorin gene present in both tetrapods and ray-finned fish. However, this gene was not detected in mouse and rat, suggesting its loss in the lineage leading to rodent murids.Mkrn2andmkrn4are located in large ancient duplicated regions in tetrapod and fish genomes, suggesting the possible involvement of ancestral vertebrate-specific genome duplication in the formation of these genes. Intriguingly, manymkrn1andmkrn2intronless retrocopies have been detected in mammals but not in other vertebrates, most of them corresponding to pseudogenes. The nature and number of zinc fingers were found to be conserved in Mkrn1 and Mkrn2 but much more variable in Mkrn4, with lineage-specific differences. RT-qPCR analysis demonstrated a highly gonad-biased expression pattern formakoringenes in medaka and zebrafish (ray-finned fishes) and amphibians, but a strong relaxation of this specificity in birds and mammals. All threemkrngenes were maternally expressed before zygotic genome activation in both medaka and zebrafish early embryos.

Conclusion

Our analysis demonstrates that themakoringene family has evolved through large-scale duplication and subsequent lineage-specific retroposition-mediated duplications in vertebrates. From the three major vertebratemkrngenes,mkrn4shows the highest evolutionary dynamics, with lineage-specific loss of zinc fingers and even complete gene elimination from certain groups of vertebrates. Comparative expression analysis strongly suggests that the ancestral E3 ubiquitin ligase function of the single copymkrngene before duplication in vertebrates was gonad-specific, with maternal expression in early embryos.
Global analysis of the eukaryotic pathways and networks regulated by Salmonella typhimurium in mouse intestinal infection in vivo
Authors: Liu Xingyin , Lu Rong , Xia Yinglin , Sun Jun
Published: January 2011

Background

Acute enteritis caused bySalmonellais a public health concern.Salmonellainfection is also known to increase the risk of inflammatory bowel diseases and cancer. Therefore, it is important to understand howSalmonellaworks in targeting eukaryotic pathways in intestinal infection. However, the global physiological function ofSalmonellatyphimurium in intestinal mucosain vivois unclear. In this study, a whole genome approach combined with bioinformatics assays was used to investigate thein vivogenetic responses of the mouse colon toSalmonella. We focused on the intestinal responses in the early stage (8 hours) and late stage (4 days) afterSalmonellainfection.

Results

Of the 28,000 genes represented on the array, our analysis of mRNA expression in mouse colon mucosa showed that a total of 856 genes were expressed differentially at 8 hours post-infection. At 4 days post-infection, a total of 7558 genes were expressed differentially. 23 differentially expressed genes from the microarray data was further examined by real-time PCR. Ingenuity Pathways Analysis identified that the most significant pathway associated with the differentially expressed genes in 8 hours post-infection is oxidative phosphorylation, which targets the mitochondria. At the late stage of infection, a series of pathways associated with immune and inflammatory response, proliferation, and apoptosis were identified, whereas the oxidative phosphorylation was shut off. Histology analysis confirmed the biological role ofSalmonella, which induced a physiological state of inflammation and proliferation in the colon mucosa through the regulation of multiple signaling pathways. Most of the metabolism-related pathways were targeted by down-regulated genes, and a general repression process of metabolic pathways was observed. Network analysis supported IFN-γ and TNF-α function as mediators of the immune/inflammatory response for host defense against pathogen.

Conclusion

Our study provides novel genome-wide transcriptional profiling data on the mouse colon mucosa's response to theSalmonella typhimuriuminfection. Building the pathways and networks of interactions between these genes help us to understand the complex interplay in the mice colon duringSalmonellainfection, and further provide new insights into the molecular cascade, which is mobilized to combatSalmonella-associated colon infectionin vivo.
Transcriptome analysis of grain-filling caryopses reveals involvement of multiple regulatory pathways in chalky grain formation in rice
Authors: Liu Xiaolu , Guo Tao , Wan Xiangyuan , Wang Haiyang , Zhu Mingzhu , Li Aili , Su Ning , Shen Yingyue , Mao Bigang , Zhai Huqu , Mao Long , Wan Jianmin
Published: January 2011

Background

Grain endosperm chalkiness of rice is a varietal characteristic that negatively affects not only the appearance and milling properties but also the cooking texture and palatability of cooked rice. However, grain chalkiness is a complex quantitative genetic trait and the molecular mechanisms underlying its formation are poorly understood.

Results

A near-isogenic line CSSL50-1 with high chalkiness was compared with its normal parental line Asominori for grain endosperm chalkiness. Physico-biochemical analyses of ripened grains showed that, compared with Asominori, CSSL50-1 contains higher levels of amylose and 8 DP (degree of polymerization) short-chain amylopectin, but lower medium length 12 DP amylopectin. Transcriptome analysis of 15 DAF (day after flowering) caryopses of the isogenic lines identified 623 differential expressed genes (P< 0.01), among which 324 genes are up-regulated and 299 down-regulated. These genes were classified into 18 major categories, with 65.3% of them belong to six major functional groups: signal transduction, cell rescue/defense, transcription, protein degradation, carbohydrate metabolism and redox homeostasis. Detailed pathway dissection demonstrated that genes involved in sucrose and starch synthesis are up-regulated, whereas those involved in non-starch polysaccharides are down regulated. Several genes involved in oxidoreductive homeostasis were found to have higher expression levels in CSSL50-1 as well, suggesting potential roles of ROS in grain chalkiness formation.

Conclusion

Extensive gene expression changes were detected during rice grain chalkiness formation. Over half of these differentially expressed genes are implicated in several important categories of genes, including signal transduction, transcription, carbohydrate metabolism and redox homeostasis, suggesting that chalkiness formation involves multiple metabolic and regulatory pathways.
Time-series clustering of gene expression in irradiated and bystander fibroblasts: an application of FBPA clustering
Authors: Ghandhi Shanaz A , Sinha Anshu , Markatou Marianthi , Amundson Sally A
Published: January 2011

Background

The radiation bystander effect is an important component of the overall biological response of tissues and organisms to ionizing radiation, but the signaling mechanisms between irradiated and non-irradiated bystander cells are not fully understood. In this study, we measured a time-series of gene expression after α-particle irradiation and applied the Feature Based Partitioning around medoids Algorithm (FBPA), a new clustering method suitable for sparse time series, to identify signaling modules that act in concert in the response to direct irradiation and bystander signaling. We compared our results with those of an alternate clustering method, Short Time series Expression Miner (STEM).

Results

While computational evaluations of both clustering results were similar, FBPA provided more biological insight. After irradiation, gene clusters were enriched for signal transduction, cell cycle/cell death and inflammation/immunity processes; but only FBPA separated clusters by function. In bystanders, gene clusters were enriched for cell communication/motility, signal transduction and inflammation processes; but biological functions did not separate as clearly with either clustering method as they did in irradiated samples. Network analysis confirmed p53 and NF-κB transcription factor-regulated gene clusters in irradiated and bystander cells and suggested novel regulators, such as KDM5B/JARID1B (lysine (K)-specific demethylase 5B) and HDACs (histone deacetylases), which could epigenetically coordinate gene expression after irradiation.

Conclusions

In this study, we have shown that a new time series clustering method, FBPA, can provide new leads to the mechanisms regulating the dynamic cellular response to radiation. The findings implicate epigenetic control of gene expression in addition to transcription factor networks.
Differential mucosal expression of Th17-related genes between the inflamed colon and ileum of patients with inflammatory bowel disease
Authors: Bogaert Sara , Laukens Debby , Peeters Harald , Melis Lode , Olievier Kim , Boon Nico , Verbruggen Gust , Vandesompele Jo , Elewaut Dirk , De Vos Martine
Published: January 2011

Background

Immunological and genetic findings implicate Th17 effector cytokines in the pathogenesis of inflammatory bowel disease (IBD). Expression of Th17 pathway-associated genes is mainly studied in colonic disease. The present study assessed the mRNA expression levels of Th17 effector cytokines (IL17A, IL17F, IL21, IL22 and IL26) and genes involved in differentiation (IL6, IL1B, TGFB1, IL23A and STAT3) and recruitment of Th17 cells (CCR6 and CCL20) by quantitative real-time PCR analysis of colonic and ileal biopsies from 22 healthy control subjects, 26 patients with Crohn's disease (CD) and 12 patients with ulcerative colitis (UC). Inflammation was quantified by measuring expression of the inflammatory mediators IL8 and TNF.

Results

Evaluation of mRNA expression levels in colonic and ileal control samples revealed that TNF, TGFB1, STAT3 and CCR6 were expressed at higher levels in the ileum than in the colon. Expression of all the Th17 pathway-associated genes was increased in inflamed colonic samples. The increased expression of these genes was predominantly observed in samples from UC patients and was associated with more intense inflammation. Although increased expression of IL17A, IL17F, IL21 and IL26 was detected in inflamed ileal samples, expression of the indispensable Th17 cell differentiation factors TGFB1 and IL23A, the signaling molecule STAT3 and the Th17 recruitment factors CCR6 and CCL20 were unchanged.

Conclusions

Our findings suggest that immune regulation is different in colonic and ileal disease, which might have important consequences for therapeutic intervention.
Mannan-binding lectin regulates dendritic cell maturation and cytokine production induced by lipopolysaccharide
Authors: Wang Mingyong , Zhang Yani , Chen Yue , Zhang Liyun , Lu Xiao , Chen Zhengliang
Published: January 2011

Background

Mannan-binding lectin (MBL) is a pattern-recognition molecule present in serum, which is involved in the innate immune defense by activating complement and promoting opsonophagocytosis. Dendritic cells (DCs) are professional antigen presenting cells (APCs) that are crucial for the initiation of adaptive immunity. Lipopolysaccharide (LPS) has been shown to be a strong activator of the inflammatory response and immune regulation. We first examined whether MBL modulated LPS-induced cellular responses, then investigated possible mechanisms of its inhibitory effect.

Results

MBL at higher concentrations (10-20 μg/ml) significantly attenuated LPS-induced maturation of monocyte-derived DCs (MDCs) and production of proinflammatory cytokines (e.g., IL-12 and TNF-α), and inhibited their ability to activate allogeneic T lymphocytes. It bound to immature MDCs at physiological calcium concentrations, and was optimal at supraphysiological calcium concentrations. MBL also bound directly to immature MDCs and attenuated the binding of LPS to the cell surfaces, resulting in decreased LPS-induced nuclear factor-κB (NF-κB) activity in these cells.

Conclusion

All these data suggest that MBL could affect the functions of DCs by modifying LPS-induced cellular responses. This study supports an important role for MBL in the regulation of adaptive immune responses and inflammatory responses.
Characterization, phylogeny, alternative splicing and expression of Sox30 gene
Authors: Han Fei , Wang Zhijian , Wu Fengrui , Liu Zhihao , Huang Baofeng , Wang Deshou
Published: January 2011

Background

Members of the Sox gene family isolated from both vertebrates and invertebrates have been proved to participate in a wide variety of developmental processes, including sex determination and differentiation. Among these members, Sox30 had been considered to exist only in mammals since its discovery, and its exact function remains unclear.

Results

Sox30 cDNA was cloned from the Nile tilapia by RT-PCR and RACE. Screening of available genome and EST databases and phylogenetic analysis showed that Sox30 also exists in non-mammalian vertebrates and invertebrates, which was further supported by synteny analyses. Tissue expression in human, mouse and tilapia suggested that Sox30 was probably a gonad-specific gene, which was also supported by the fact that Sox30 EST sequences were obtained from gonads of the animal species. In addition, four alternatively spliced isoforms were isolated from tilapia gonad. Their temporal and spatial expression patterns during normal and sex reversed gonadal development were investigated by RT-PCR and in situ hybridization. Our data suggest that expressions of Sox30 isoforms are related to stage and phenotypic-sex, observed in the germ cells of male gonad and in somatic cells of the female gonad.

Conclusions

Sox30 is not a gene only existed in mammals, but exists widely throughout the animal kingdom as supported by our bioinformatic, phylogenetic and syntenic analyses. It is very likely that Sox30 is expressed exclusively in gonads. Expression analyses revealed that Sox30 may be involved in female and male gonadal development at different stages by alternative splicing.
Gene family structure, expression and functional analysis of HD-Zip III genes in angiosperm and gymnosperm forest trees
Authors: Côté Caroline L , Boileau Francis , Roy Vicky , Ouellet Mario , Levasseur Caroline , Morency Marie-Josée , Cooke Janice EK , Séguin Armand , MacKay John J
Published: January 2011

Background

Class III Homeodomain Leucine Zipper (HD-Zip III) proteins have been implicated in the regulation of cambium identity, as well as primary and secondary vascular differentiation and patterning in herbaceous plants. They have been proposed to regulate wood formation but relatively little evidence is available to validate such a role. We characterised and compared HD-Zip III gene family in an angiosperm tree,Populusspp. (poplar), and the gymnospermPicea glauca(white spruce), representing two highly evolutionarily divergent groups.

Results

Full-length cDNA sequences were isolated from poplar and white spruce. Phylogenetic reconstruction indicated that some of the gymnosperm sequences were derived from lineages that diverged earlier than angiosperm sequences, and seem to have been lost in angiosperm lineages. Transcript accumulation profiles were assessed by RT-qPCR on tissue panels from both species and in poplar trees in response to an inhibitor of polar auxin transport. The overall transcript profiles HD-Zip III complexes in white spruce and poplar exhibited substantial differences, reflecting their evolutionary history. Furthermore, two poplar sequences homologous to HD-Zip III genes involved in xylem development inArabidopsisandZinniawere over-expressed in poplar plants.PtaHB1over-expression produced noticeable effects on petiole and primary shoot fibre development, suggesting thatPtaHB1is involved in primary xylem development. We also obtained evidence indicating that expression ofPtaHB1affected the transcriptome by altering the accumulation of 48 distinct transcripts, many of which are predicted to be involved in growth and cell wall synthesis. Most of them were down-regulated, as was the case for several of the poplar HD-Zip III sequences. No visible physiological effect of over-expression was observed onPtaHB7transgenic trees, suggesting thatPtaHB1andPtaHB7likely have distinct roles in tree development, which is in agreement with the functions that have been assigned to close homologs in herbaceous plants.

Conclusions

This study provides an overview of HD-zip III genes related to woody plant development and identifies sequences putatively involved in secondary vascular growth in angiosperms and in gymnosperms. These gene sequences are candidate regulators of wood formation and could be a source of molecular markers for tree breeding related to wood properties.
A molecular recombination map of Antirrhinum majus
Authors: Schwarz-Sommer Zsuzsanna , Gübitz Thomas , Weiss Julia , Gómez-di-Marco Perla , Delgado-Benarroch Luciana , Hudson Andrew , Egea-Cortines Marcos
Published: January 2011

Background

Genetic recombination maps provide important frameworks for comparative genomics, identifying gene functions, assembling genome sequences and for breeding. The molecular recombination map currently available for the model eudicot Antirrhinum majus is the result of a cross with Antirrhinum molle, limiting its usefulness within A. majus.

Results

We created a molecular linkage map of A. majus based on segregation of markers in the F2 population of two inbred lab strains of A. majus. The resulting map consisted of over 300 markers in eight linkage groups, which could be aligned with a classical recombination map and the A. majus karyotype. The distribution of recombination frequencies and distorted transmission of parental alleles differed from those of a previous inter-species hybrid. The differences varied in magnitude and direction between chromosomes, suggesting that they had multiple causes. The map, which covered an estimated of 95% of the genome with an average interval of 2 cM, was used to analyze the distribution of a newly discovered family of MITE transposons and tested for its utility in positioning seven mutations that affect aspects of plant size.

Conclusions

The current map has an estimated interval of 1.28 Mb between markers. It shows a lower level of transmission ratio distortion and a longer length than the previous inter-species map, making it potentially more useful. The molecular recombination map further indicates that the IDLE MITE transposons are distributed throughout the genome and are relatively stable. The map proved effective in mapping classical morphological mutations of A. majus.
Isolation and functional characterization of CE1 binding proteins
Authors: Lee Sun-ji , Park Ji Hye , Lee Mi Hun , Yu Ji-hyun , Kim Soo Young
Published: January 2011

Background

Abscisic acid (ABA) is a plant hormone that controls seed germination, protective responses to various abiotic stresses and seed maturation. The ABA-dependent processes entail changes in gene expression. Numerous genes are regulated by ABA, and promoter analyses of the genes revealed thatcis-elements sharing the ACGTGGC consensus sequence are ubiquitous among ABA-regulated gene promoters. The importance of the core sequence, which is generally known as ABA response element (ABRE), has been demonstrated by various experiments, and its cognate transcription factors known as ABFs/AREBs have been identified. Although necessary, ABRE alone is not sufficient, and anothercis-element known as "coupling element (CE)" is required for full range ABA-regulation of gene expression. Several CEs are known. However, despite their importance, the cognate transcription factors mediating ABA response via CEs have not been reported to date. Here, we report the isolation of transcription factors that bind one of the coupling elements, CE1.

Results

To isolate CE1 binding proteins, we carried out yeast one-hybrid screens. Reporter genes containing a trimer of the CE1 element were prepared and introduced into a yeast strain. The yeast was transformed with library DNA that represents RNA isolated from ABA-treated Arabidopsis seedlings. From the screen of 3.6 million yeast transformants, we isolated 78 positive clones. Analysis of the clones revealed that a group of AP2/ERF domain proteins binds the CE1 element. We investigated their expression patterns and analyzed their overexpression lines to investigate thein vivofunctions of the CE element binding factors (CEBFs). Here, we show that one of the CEBFs, AtERF13, confers ABA hypersensitivity in Arabidopsis, whereas two other CEBFs enhance sugar sensitivity.

Conclusions

Our results indicate that a group of AP2/ERF superfamily proteins interacts with CE1. Several CEBFs are known to mediate defense or abiotic stress response, but the physiological functions of other CEBFs remain to be determined. Ourin vivofunctional analysis of several CEBFs suggests that they are likely to be involved in ABA and/or sugar response. Together with previous results reported by others, our current data raise an interesting possibility that the coupling element CE1 may function not only as an ABRE but also as an element mediating biotic and abiotic stress responses.
A var2 leaf variegation suppressor locus, SUPPRESSOR OF VARIEGATION3, encodes a putative chloroplast translation elongation factor that is important for chloroplast development in the cold
Authors: Liu Xiayan , Rodermel Steve R , Yu Fei
Published: January 2011

Background

The Arabidopsis var2 mutant displays a unique green and white/yellow leaf variegation phenotype and lacks VAR2, a chloroplast FtsH metalloprotease. We are characterizing second-site var2 genetic suppressors as means to better understand VAR2 function and to study the regulation of chloroplast biogenesis.

Results

In this report, we show that the suppression of var2 variegation in suppressor line TAG-11 is due to the disruption of the SUPPRESSOR OF VARIEGATION3 (SVR3) gene, encoding a putative TypA-like translation elongation factor. SVR3 is targeted to the chloroplast and svr3 single mutants have uniformly pale green leaves at 22°C. Consistent with this phenotype, most chloroplast proteins and rRNA species in svr3 have close to normal accumulation profiles, with the notable exception of the Photosystem II reaction center D1 protein, which is present at greatly reduced levels. When svr3 is challenged with chilling temperature (8°C), it develops a pronounced chlorosis that is accompanied by abnormal chloroplast rRNA processing and chloroplast protein accumulation. Double mutant analysis indicates a possible synergistic interaction between svr3 and svr7, which is defective in a chloroplast pentatricopeptide repeat (PPR) protein.

Conclusions

Our findings, on one hand, reinforce the strong genetic link between VAR2 and chloroplast translation, and on the other hand, point to a critical role of SVR3, and possibly some aspects of chloroplast translation, in the response of plants to chilling stress.
Prognostic factors and monomicrobial necrotizing fasciitis: gram-positive versus gram-negative pathogens
Authors: Lee Ching-Yu , Kuo Liang-Tseng , Peng Kuo-Ti , Hsu Wei-Hsiu , Huang Tsan-Wen , Chou Ying-Chao
Published: January 2011

Background

Monomicrobial necrotizing fasciitis is rapidly progressive and life-threatening. This study was undertaken to ascertain whether the clinical presentation and outcome for patients with this disease differ for those infected with a gram-positive as compared to gram-negative pathogen.

Methods

Forty-six patients with monomicrobial necrotizing fasciitis were examined retrospectively from November 2002 to January 2008. All patients received adequate broad-spectrum antibiotic therapy, aggressive resuscitation, prompt radical debridement and adjuvant hyperbaric oxygen therapy. Eleven patients were infected with a gram-positive pathogen (Group 1) and 35 patients with a gram-negative pathogen (Group 2).

Results

Group 2 was characterized by a higher incidence of hemorrhagic bullae and septic shock, higher APACHE II scores at 24 h post-admission, a higher rate of thrombocytopenia, and a higher prevalence of chronic liver dysfunction. Gouty arthritis was more prevalent in Group 1. For non-survivors, the incidences of chronic liver dysfunction, chronic renal failure and thrombocytopenia were higher in comparison with those for survivors. Lower level of serum albumin was also demonstrated in the non-survivors as compared to those in survivors.

Conclusions

Pre-existing chronic liver dysfunction, chronic renal failure, thrombocytopenia and hypoalbuminemia, and post-operative dependence on mechanical ventilation represent poor prognostic factors in monomicrobial necrotizing fasciitis. Patients with gram-negative monobacterial necrotizing fasciitis present with more fulminant sepsis.
Circulating endothelial cells are an early predictor in renal cell carcinoma for tumor response to sunitinib
Authors: Gruenwald Viktor , Beutel Gernot , Schuch-Jantsch Susanne , Reuter Christoph , Ivanyi Philipp , Ganser Arnold , Haubitz Marion
Published: January 2011

Background

Tyrosine kinase inhibitors (TKI) have enriched the therapeutic options in patients with renal cell carcinoma (RCC), which frequently induce morphological changes in tumors. However, only little is known about the biological activity of TKI. Circulating endothelial cells (CEC) have been associated with endothelial damage and, hence, may serve as a putative marker for the biological activity of TKI. The main objective of our study was to evaluate the predictive value of CEC, monocytes, and soluble vascular endothelial growth factor receptor (sVEGFR)-2 in RCC patients receiving sunitinib treatment.

Methods

Analyses of CEC, monocytes, and sVEGFR-2 were accomplished for twenty-six consecutive patients with metastatic RCC who received treatment with sunitinib (50 mg, 4 wks on 2 wks off schedule) at our institution in 2005 and 2006.

Results

In RCC patients CEC are elevated to 49 ± 44/ml (control 8 ± 8/ml; P = 0.0001). Treatment with sunitinib is associated with an increase in CEC within 28 days of treatment in patients with a Progression free survival (PFS) above the median to 111 ± 61 (P = 0.0109), whereas changes in patients with a PFS below the median remain insignificant 69 ± 61/ml (P = 0.1848). Monocytes and sVEGFR2 are frequently altered upon sunitinib treatment, but fail to correlate with clinical response, defined by PFS above or below the median.

Conclusions

Sunitinib treatment is associated with an early increase of CEC in responding patients, suggesting superior endothelial cell damage in these patients as a putative predictive biomarker.
HIV and Hepatitis B and C incidence rates in US correctional populations and high risk groups: a systematic review and meta-analysis
Authors: Gough Ethan , Kempf Mirjam C , Graham Laura , Manzanero Marvin , Hook Edward W , Bartolucci Al , Chamot Eric
Published: January 2011

Background

High Human Immunodeficiency Virus (HIV) prevalence and high risk behaviors have been well documented within United States (US) correctional systems. However, uncertainty remains regarding the extent to which placing people in prison or jail increases their risk of HIV infection, and regarding which inmate populations experience an increased incidence of HIV. Describing these dynamics more clearly is essential to understanding how inmates and former detainees may be a source for further spread of HIV to the general US population.

Methods

The authors conducted a systematic review and meta-analysis of studies describing HIV incidence in US correctional facility residents and, for comparison, in high risk groups for HIV infection, such as non-incarcerated intravenous drug users (IVDU) and men who have sex with men (MSM) in the US. HIV incidence rates were further compared with Hepatitis B and Hepatitis C Virus rates in these same populations.

Results

Thirty-six predominantly prospective cohort studies were included. Across all infection outcomes, continuously incarcerated inmates and treatment recruited IVDU showed the lowest incidence, while MSM and street recruited IVDU showed the highest. HIV incidence was highest among inmates released and re-incarcerated. Possible sources of heterogeneity identified among HIV studies were risk population and race.

Conclusions

Although important literature gaps were found, current evidence suggests that policies and interventions for HIV prevention in correctional populations should prioritize curtailing risk of infection during the post-release period. Future research should evaluate HIV incidence rates in inmate populations, accounting for proportion of high risk sub-groups.
A rare case of metastatic renal carcinoid
Authors: Kato Yoshiharu , Nakamura Kogenta , Yamada Yoshiaki , Nishikawa Genya , Yoshizawa Takahiko , Zennnami Kenji , Katsuda Remi , Tobiume Motoi , Aoki Shigeyuki , Taki Tomohiro , Honda Nobuaki
Published: January 2011

Background

Carcinoid is an endocrine cell tumor with low-grade atypia, which is generally a low-grade malignant cancer with a good prognosis. Metastatic renal carcinoid is even rarer than primary carcinoids.

Case presentation

We present our experience of a patient with metastatic renal carcinoid from the gastrointestinal tract.

Conclusions

The carcinoid tumor of the kidney in our patient, who had a history of liver metastasis from rectal carcinoid, was considered metastatic based on the pathological findings.