bluuebunny/crossref_metadata_2025_split huggingface dataset:
A bag-of-words approach for Drosophila gene expression pattern annotation
Authors: Ji Shuiwang , Li Ying-Xin , Zhou Zhi-Hua , Kumar Sudhir , Ye Jieping 
Published: April 2009

AbstractBackgroundDrosophilagene expression pattern images document the spatiotemporal dynamics of gene expression during embryogenesis. A comparative analysis of these images could provide a fundamentally important way for studying the regulatory networks governing development. To facilitate pattern comparison and searching, groups of images in the BerkeleyDrosophilaGenome Project (BDGP) high-throughput study were annotated with a variable number of anatomical terms manually using a controlled vocabulary. Considering that the number of available images is rapidly increasing, it is imperative to design computational methods to automate this task.ResultsWe present a computational method to annotate gene expression pattern images automatically. The proposed method uses the bag-of-words scheme to utilize the existing information on pattern annotation and annotates images using a model that exploits correlations among terms. The proposed method can annotate images individually or in groups (e.g., according to the developmental stage). In addition, the proposed method can integrate information from different two-dimensional views of embryos. Results on embryonic patterns from BDGP data demonstrate that our method significantly outperforms other methods.ConclusionThe proposed bag-of-words scheme is effective in representing a set of annotations assigned to a group of images, and the model employed to annotate images successfully captures the correlations among different controlled vocabulary terms. The integration of existing annotation information from multiple embryonic views improves annotation performance.
Centrosome proteins form an insoluble perinuclear matrix during muscle cell differentiation
Authors: Srsen Vlastimil , Fant Xavier , Heald Rebecca , Rabouille Catherine , Merdes Andreas 
Published: April 2009

Abstract

Background
Muscle fibres are formed by elongation and fusion of myoblasts into myotubes. During this differentiation process, the cytoskeleton is reorganized, and proteins of the centrosome re-localize to the surface of the nucleus. The exact timing of this event, and the underlying molecular mechanisms are still poorly understood.

Results
We performed studies on mouse myoblast cell lines that were induced to differentiate in culture, to characterize the early events of centrosome protein re-localization. We demonstrate that this re-localization occurs already at the single cell stage, prior to fusion into myotubes. Centrosome proteins that accumulate at the nuclear surface form an insoluble matrix that can be reversibly disassembled if isolated nuclei are exposed to mitotic cytoplasm from Xenopus egg extract. Our microscopy data suggest that this perinuclear matrix of centrosome proteins consists of a system of interconnected fibrils.

Conclusion
Our data provide new insights into the reorganization of centrosome proteins during muscular differentiation, at the structural and biochemical level. Because we observe that centrosome protein re-localization occurs early during differentiation, we believe that it is of functional importance for the reorganization of the cytoskeleton in the differentiation process.
Mouse H6 Homeobox 1 (Hmx1) mutations cause cranial abnormalities and reduced body mass
Authors: Munroe Robert J , Prabhu Vinay , Acland Greg M , Johnson Kenneth R , Harris Belinda S , O'Brien Tim P , Welsh Ian C , Noden Drew M , Schimenti John C 
Published: April 2009

Abstract

Background
The H6 homeobox genes Hmx1, Hmx2, and Hmx3 (also known as Nkx5-3; Nkx5-2 and Nkx5-1, respectively), compose a family within the NKL subclass of the ANTP class of homeobox genes. Hmx gene family expression is mostly limited to sensory organs, branchial (pharyngeal) arches, and the rostral part of the central nervous system. Targeted mutation of either Hmx2 or Hmx3 in mice disrupts the vestibular system. These tandemly duplicated genes have functional overlap as indicated by the loss of the entire vestibular system in double mutants. Mutants have not been described for Hmx1, the most divergent of the family.

Results
Dumbo (dmbo) is a semi-lethal mouse mutation that was recovered in a forward genetic mutagenesis screen. Mutants exhibit enlarged ear pinnae with a distinctive ventrolateral shift. Here, we report on the basis of this phenotype and other abnormalities in the mutant, and identify the causative mutation as being an allele of Hmx1. Examination of dumbo skulls revealed only subtle changes in cranial bone morphology, namely hyperplasia of the gonial bone and irregularities along the caudal border of the squamous temporal bone. Other nearby otic structures were unaffected. The semilethality of dmbo/dmbo mice was found to be ~40%, occured perinatally, and was associated with exencephaly. Surviving mutants of both sexes exhibited reduced body mass from ~3 days postpartum onwards. Most dumbo adults were microphthalmic. Recombinant animals and specific deletion-bearing mice were used to map the dumbo mutation to a 1.8 Mb region on Chromosome 5. DNA sequencing of genes in this region revealed a nonsense mutation in the first exon of H6 Homeobox 1 (Hmx1; also Nkx5-3). An independent spontaneous allele called misplaced ears (mpe) was also identified, confirming Hmx1 as the responsible mutant gene.

Conclusion
The divergence of Hmx1 from its paralogs is reflected by different and diverse developmental roles exclusive of vestibular involvement. Additionally, these mutant Hmx1 alleles represent the first mouse models of a recently-discovered Oculo-Auricular syndrome caused by mutation of the orthologous human gene.
Natural variation of outcrossing in the hermaphroditic nematode Pristionchus pacificus
Authors: Click Arielle , Savaliya Chandni H , Kienle Simone , Herrmann Matthias , Pires-daSilva Andre 
Published: April 2009

Abstract

Background
Evolution of selfing can be associated with an increase in fixation of deleterious mutations, which in certain conditions can lead to species extinction. In nematodes, a few species evolved self-fertilization independently, making them excellent model systems to study the evolutionary consequences of this type of mating system.

Results
Here we determine various parameters that influence outcrossing in the hermaphroditic nematode Pristionchus pacificus and compare them to the better known Caenorhabditis elegans. These nematode species are distinct in terms of genetic diversity, which could be explained by differences in outcrossing rates. We find that, similarly to C. elegans, P. pacificus males are generated at low frequencies from self-fertilizing hermaphrodites and are relatively poor mating partners. Furthermore, crosses between different isolates reveal that hybrids have lower brood sizes than the pure strains, which is a sign of outbreeding depression. In contrast to C. elegans, P. pacificus has lower brood sizes and the male X-bearing sperm is able to outcompete the X-nullo sperm.

Conclusion
The results indicate that there is no evidence of any selection acting very strongly on P. pacificus males.
Functional annotation of the human retinal pigment epithelium transcriptome
Authors: Booij Judith C , van Soest Simone , Swagemakers Sigrid MA , Essing Anke HW , Verkerk Annemieke JMH , van der Spek Peter J , Gorgels Theo GMF , Bergen Arthur AB 
Published: April 2009

Abstract

Background
To determine level, variability and functional annotation of gene expression of the human retinal pigment epithelium (RPE), the key tissue involved in retinal diseases like age-related macular degeneration and retinitis pigmentosa. Macular RPE cells from six selected healthy human donor eyes (aged 63–78 years) were laser dissected and used for 22k microarray studies (Agilent technologies). Data were analyzed with Rosetta Resolver, the web tool DAVID and Ingenuity software.

Results
In total, we identified 19,746 array entries with significant expression in the RPE. Gene expression was analyzed according to expression levels, interindividual variability and functionality. A group of highly (n = 2,194) expressed RPE genes showed an overrepresentation of genes of the oxidative phosphorylation, ATP synthesis and ribosome pathways. In the group of moderately expressed genes (n = 8,776) genes of the phosphatidylinositol signaling system and aminosugars metabolism were overrepresented. As expected, the top 10 percent (n = 2,194) of genes with the highest interindividual differences in expression showed functional overrepresentation of the complement cascade, essential in inflammation in age-related macular degeneration, and other signaling pathways. Surprisingly, this same category also includes the genes involved in Bruch's membrane (BM) composition. Among the top 10 percent of genes with low interindividual differences, there was an overrepresentation of genes involved in local glycosaminoglycan turnover.

Conclusion
Our study expands current knowledge of the RPE transcriptome by assigning new genes, and adding data about expression level and interindividual variation. Functional annotation suggests that the RPE has high levels of protein synthesis, strong energy demands, and is exposed to high levels of oxidative stress and a variable degree of inflammation. Our data sheds new light on the molecular composition of BM, adjacent to the RPE, and is useful for candidate retinal disease gene identification or gene dose-dependent therapeutic studies.
Small noncoding RNA GcvB is a novel regulator of acid resistance in Escherichia coli
Authors: Jin Ye , Watt Rory M , Danchin Antoine , Huang Jian-dong 
Published: April 2009

AbstractBackgroundThe low pH environment of the human stomach is lethal for most microorganisms; but notEscherichia coli, which can tolerate extreme acid stress. Acid resistance inE. coliis hierarchically controlled by numerous regulators among which are small noncoding RNAs (sncRNA).ResultsIn this study, we individually deleted seventy-nine sncRNA genes from theE. coliK12-MG1655 chromosome, and established a single-sncRNA gene knockout library. By systematically screening the sncRNA mutant library, we show that the sncRNA GcvB is a novel regulator of acid resistance inE. coli. We demonstrate that GcvB enhances the ability ofE. colito survive low pH by upregulating the levels of the alternate sigma factor RpoS.ConclusionGcvB positively regulates acid resistance by affecting RpoS expression. These data advance our understanding of the sncRNA regulatory network involved in modulating acid resistance inE. coli.
The γ-gliadin multigene family in common wheat (Triticum aestivum) and its closely related species
Authors: Qi Peng-Fei , Wei Yu-Ming , Ouellet Thérèse , Chen Qing , Tan Xin , Zheng You-Liang 
Published: April 2009

Abstract

Background
The unique properties of wheat flour primarily depend on gluten, which is the most important source of protein for human being. γ-Gliadins have been considered to be the most ancient of the wheat gluten family. The complex family structure of γ-gliadins complicates the determination of their function. Moreover, γ-gliadins contain several sets of celiac disease epitopes. However, no systematic research has been conducted yet.

Results
A total of 170 γ-gliadin genes were isolated from common wheat and its closely related species, among which 138 sequences are putatively functional. The ORF lengths of these sequences range from 678 to 1089 bp, and the repetitive region is mainly responsible for the size heterogeneity of γ-gliadins. The repeat motif P(Q/L/S/T/I/V/R/A)F(S/Y/V/Q/I/C/L)P(R/L/S/T/H/C/Y)Q
1–2
(P(S/L/T/A/F/H)QQ)
1–2is repeated from 7 to 22 times. Sequence polymorphism and linkage disequilibrium analyses show that γ-gliadins are highly diverse. Phylogenic analyses indicate that there is no obvious discrimination between Sitopsis and Ae. tauschii at the Gli-1 loci, compared with diploid wheat. According to the number and placement of cysteine residues, we defined nine cysteine patterns and 17 subgroups. Alternatively, we classified γ-gliadins into two types based on the length of repetitive domain. Amino acid composition analyses indicate that there is a wide range of essential amino acids in γ-gliadins, and those γ-gliadins from subgroup SG-10 and SG-12 and γ-gliadins with a short repetitive domain are more nutritional. A screening of toxic epitopes shows that γ-gliadins with a pattern of C9 and γ-gliadins with a short repetitive domain almost lack any epitopes.

Conclusion
γ-Gliadin sequences in wheat and closely related Aegilops species are diverse. Each group/subgroup contributes differently to nutritional quality and epitope content. It is suggested that the genes with a short repetitive domain are more nutritional and valuable. Therefore, it is possible to breed wheat varieties, the γ-gliadins of which are less, even non-toxic and more nutritional.
Electro-acupuncture promotes survival, differentiation of the bone marrow mesenchymal stem cells as well as functional recovery in the spinal cord-transected rats
Authors: Ding Ying , Yan Qing , Ruan Jing-Wen , Zhang Yan-Qing , Li Wen-Jie , Zhang Yu-Jiao , Li Yan , Dong Hongxin , Zeng Yuan-Shan 
Published: April 2009

Abstract

Background
Bone marrow mesenchymal stem cells (MSCs) are one of the potential tools for treatment of the spinal cord injury; however, the survival and differentiation of MSCs in an injured spinal cord still need to be improved. In the present study, we investigated whether Governor Vessel electro-acupuncture (EA) could efficiently promote bone marrow mesenchymal stem cells (MSCs) survival and differentiation, axonal regeneration and finally, functional recovery in the transected spinal cord.

Results
The spinal cords of adult Sprague-Dawley (SD) rats were completely transected at T10, five experimental groups were performed: 1. sham operated control (Sham-control); 2. operated control (Op-control); 3. electro-acupuncture treatment (EA); 4. MSCs transplantation (MSCs); and 5. MSCs transplantation combined with electro-acupuncture (MSCs+EA). After 2-8 weeks of MSCs transplantation plus EA treatment, we found that the neurotrophin-3 (NT-3), cAMP level, the differentiation of MSCs, the 5-HT positive and CGRP positive nerve fibers in the lesion site and nearby tissue of injured spinal cord were significantly increased in the MSCs+EA group as compared to the group of the MSCs transplantation or the EA treated alone. Furthermore, behavioral test and spinal cord evoked potentials detection demonstrated a significantly functional recovery in the MSCs +EA group.

Conclusion
These results suggest that EA treatment may promote grafted MSCs survival and differentiation; MSCs transplantation combined with EA treatment could promote axonal regeneration and partial locomotor functional recovery in the transected spinal cord in rats and indicate a promising avenue of treatment of spinal cord injury.
Reasons of general practitioners for not prescribing lipid-lowering medication to patients with diabetes: a qualitative study
Authors: AB Elisabeth , Denig Petra , van Vliet Ton , Dekker Janny H 
Published: April 2009

Abstract

Background
Lipid-lowering medication remains underused, even in high-risk populations. The objective of this study was to determine factors underlying general practitioners' decisions not to prescribe such drugs to patients with type 2 diabetes.

Methods
A qualitative study with semi-structured interviews using real cases was conducted to explore reasons for not prescribing lipid-lowering medication after a guideline was distributed that recommended the use of statins in most patients with type 2 diabetes. Seven interviews were conducted with general practitioners (GPs) in The Netherlands, and analysed using an analytic inductive approach.

Results
Reasons for not-prescribing could be divided into patient and physician-attributed factors. According to the GPs, some patients do not follow-up on agreed medication and others object to taking lipid-lowering medication, partly for legitimate reasons such as expected or perceived side effects. Furthermore, the GPs themselves perceived reservations for prescribing lipid-lowering medication in patients with short life expectancy, expected compliance problems or near goal lipid levels. GPs sometimes postponed the start of treatment because of other priorities. Finally, barriers were seen in the GPs' practice organisation, and at the primary-secondary care interface.

Conclusion
Some of the barriers mentioned by GPs seem to be valid reasons, showing that guideline non-adherence can be quite rational. On the other hand, treatment quality could improve by addressing issues, such as lack of knowledge or motivation of both the patient and the GP. More structured management in general practice may also lead to better treatment.
Activation of P2X7-mediated apoptosis Inhibits DMBA/TPA-induced formation of skin papillomas and cancer in mice
Authors: Fu Wen , McCormick Tom , Qi Xiaoping , Luo Liping , Zhou Lingyin , Li Xin , Wang Bing-Cheng , Gibbons Heidi E , Abdul-Karim Fadi W , Gorodeski George I 
Published: April 2009

AbstractBackgroundThe study tested the hypothesis that apoptosis can prevent and control growth of neoplastic cells. Previous studies in-vitro have shown that the pro-apoptotic P2X7receptor regulates growth of epithelial cells. The specific objective of the present study was to understand to what degree the P2X7system controls development and growth of skin cancer in vivo, and what cellular and molecular mechanisms are involved in the P2X7action.MethodsSkin neoplasias in mice (papillomas, followed by squamous spindle-cell carcinomas) were induced by local application of DMBA/TPA. Experiments in-vitro utilized cultured epidermal keratinocytes generated from wild-type or from P2X7-null mice. Assays involved protein immunostaining and Western blots; mRNA real-time qPCR; and apoptosis (evaluated in situ by TUNEL and quantified in cultured keratinocytes as solubilized DNA or by ELISA). Changes in cytosolic calcium or in ethidium bromide influx (P2X7pore formation) were determined by confocal laser microscopy.Results(a) Co-application on the skin of the P2X7specific agonist BzATP inhibited formation of DMBA/TPA-induced skin papillomas and carcinomas. At the completion of study (week 28) the proportion of living animals with cancers in the DMBA/TPA group was 100% compared to 43% in the DMBA/TPA+BzATP group. (b) In the normal skin BzATP affected mainly P2X7-receptor – expressing proliferating keratinocytes, where it augmented apoptosis without evoking inflammatory changes. (c) In BzATP-treated mice the degree of apoptosis was lesser in cancer than in normal or papilloma keratinocytes. (d) Levels of P2X7receptor, protein and mRNA were 4–5 fold lower in cancer tissues than in normal mouse tissues. (e) In cultured mouse keratinocytes BzATP induced apoptosis, formation of pores in the plasma membrane, and facilitated prolonged calcium influx. (f) The BzATP-induced apoptosis, pore-formation and augmented calcium influx had similar dose-dependence for BzATP. (g) Pore formation and the augmented calcium influx were depended on the expression of the P2X7receptor, while the BzATP-induced apoptosis depended on calcium influx. (h) The BzATP-induced apoptosis could be blocked by co-treatment with inhibitors of caspase-9 and caspase-3, but not of caspase-8.Conclusion(a) P2X7-dependent apoptosis is an important mechanism that controls the development and progression of epidermal neoplasia in the mouse. (b) The P2X7-dependent apoptosis is mediated by calcium influx via P2X7pores, and involves the caspase-9 (mitochondrial) pathway. (c) The diminished pro-apoptotic effect of BzATP in mouse cancer keratinocytes is possibly the result of low expression of the P2X7receptor. (d) Activation of P2X7-dependent apoptosis, e.g. with BzATP could be a novel chemotherapeutic growth-preventive modality for papillomas and epithelial cancers in vivo.
A comparison of synthetic oligodeoxynucleotides, DNA fragments and AAV-1 for targeted episomal and chromosomal gene repair
Authors: Leclerc Xavier , Danos Olivier , Scherman Daniel , Kichler Antoine 
Published: April 2009

Abstract

Background
Current strategies for gene therapy of inherited diseases consist in adding functional copies of the gene that is defective. An attractive alternative to these approaches would be to correct the endogenous mutated gene in the affected individual. This study presents a quantitative comparison of the repair efficiency using different forms of donor nucleic acids, including synthetic DNA oligonucleotides, double stranded DNA fragments with sizes ranging from 200 to 2200 bp and sequences carried by a recombinant adeno-associated virus (rAAV-1). Evaluation of each gene repair strategy was carried out using two different reporter systems, a mutated eGFP gene or a dual construct with a functional eGFP and an inactive luciferase gene, in several different cell systems. Gene targeting events were scored either following transient co-transfection of reporter plasmids and donor DNAs, or in a system where a reporter construct was stably integrated into the chromosome.

Results
In both episomal and chromosomal assays, DNA fragments were more efficient at gene repair than oligonucleotides or rAAV-1. Furthermore, the gene targeting frequency could be significantly increased by using DNA repair stimulating drugs such as doxorubicin and phleomycin.

Conclusion
Our results show that it is possible to obtain repair frequencies of 1% of the transfected cell population under optimized transfection protocols when cells were pretreated with phleomycin using rAAV-1 and dsDNA fragments.
Gene Composer: database software for protein construct design, codon engineering, and gene synthesis
Authors: Lorimer Don , Raymond Amy , Walchli John , Mixon Mark , Barrow Adrienne , Wallace Ellen , Grice Rena , Burgin Alex , Stewart Lance 
Published: April 2009

Abstract

Background
To improve efficiency in high throughput protein structure determination, we have developed a database software package, Gene Composer, which facilitates the information-rich design of protein constructs and their codon engineered synthetic gene sequences. With its modular workflow design and numerous graphical user interfaces, Gene Composer enables researchers to perform all common bio-informatics steps used in modern structure guided protein engineering and synthetic gene engineering.

Results
An interactive Alignment Viewer allows the researcher to simultaneously visualize sequence conservation in the context of known protein secondary structure, ligand contacts, water contacts, crystal contacts, B-factors, solvent accessible area, residue property type and several other useful property views. The Construct Design Module enables the facile design of novel protein constructs with altered N- and C-termini, internal insertions or deletions, point mutations, and desired affinity tags. The modifications can be combined and permuted into multiple protein constructs, and then virtually cloned in silico into defined expression vectors. The Gene Design Module uses a protein-to-gene algorithm that automates the back-translation of a protein amino acid sequence into a codon engineered nucleic acid gene sequence according to a selected codon usage table with minimal codon usage threshold, defined G:C% content, and desired sequence features achieved through synonymous codon selection that is optimized for the intended expression system. The gene-to-oligo algorithm of the Gene Design Module plans out all of the required overlapping oligonucleotides and mutagenic primers needed to synthesize the desired gene constructs by PCR, and for physically cloning them into selected vectors by the most popular subcloning strategies.

Conclusion
We present a complete description of Gene Composer functionality, and an efficient PCR-based synthetic gene assembly procedure with mis-match specific endonuclease error correction in combination with PIPE cloning. In a sister manuscript we present data on how Gene Composer designed genes and protein constructs can result in improved protein production for structural studies.