bluuebunny/crossref_metadata_2025_split huggingface dataset:
Meta-analysis of breast cancer microarray studies in conjunction with conserved cis-elements suggest patterns for coordinate regulation
Authors: Smith David D , Sætrom Pål , Snøve Ola , Lundberg Cathryn , Rivas Guillermo E , Glackin Carlotta , Larson Garrett P 
Published: January 2008

AbstractBackgroundGene expression measurements from breast cancer (BrCa) tumors are established clinical predictive tools to identify tumor subtypes, identify patients showing poor/good prognosis, and identify patients likely to have disease recurrence. However, diverse breast cancer datasets in conjunction with diagnostic clinical arrays show little overlap in the sets of genes identified. One approach to identify a set of consistently dysregulated candidate genes in these tumors is to employ meta-analysis of multiple independent microarray datasets. This allows one to compare expression data from a diverse collection of breast tumor array datasets generated on either cDNA or oligonucleotide arrays.ResultsWe gathered expression data from 9 published microarray studies examining estrogen receptor positive (ER+) and estrogen receptor negative (ER-) BrCa tumor cases from the Oncomine database. We performed a meta-analysis and identified genes that were universally up or down regulated with respect to ER+ versus ER- tumor status. We surveyed both the proximal promoter and 3' untranslated regions (3'UTR) of our top-ranking genes in each expression group to test whether common sequence elements may contribute to the observed expression patterns. Utilizing a combination of known transcription factor binding sites (TFBS), evolutionarily conserved mammalian promoter and 3'UTR motifs, and microRNA (miRNA) seed sequences, we identified numerous motifs that were disproportionately represented between the two gene classes suggesting a common regulatory network for the observed gene expression patterns.ConclusionSome of the genes we identified distinguish key transcripts previously seen in array studies, while others are newly defined. Many of the genes identified as overexpressed in ER- tumors were previously identified as expression markers for neoplastic transformation in multiple human cancers. Moreover, our motif analysis identified a collection of specificcis-acting target sites which may collectively play a role in the differential gene expression patterns observed in ER+ versus ER- breast cancer tumors. Importantly, the gene sets and associated DNA motifs provide a starting point with which to explore the mechanistic basis for the observed expression patterns in breast tumors.
E-CAI: a novel server to estimate an expected value of Codon Adaptation Index (eCAI)
Authors: Puigbò Pere , Bravo Ignacio G , Garcia-Vallvé Santiago 
Published: January 2008

Abstract

Background
The Codon Adaptation Index (CAI) is a measure of the synonymous codon usage bias for a DNA or RNA sequence. It quantifies the similarity between the synonymous codon usage of a gene and the synonymous codon frequency of a reference set. Extreme values in the nucleotide or in the amino acid composition have a large impact on differential preference for synonymous codons. It is thence essential to define the limits for the expected value of CAI on the basis of sequence composition in order to properly interpret the CAI and provide statistical support to CAI analyses. Though several freely available programs calculate the CAI for a given DNA sequence, none of them corrects for compositional biases or provides confidence intervals for CAI values.

Results
The E-CAI server, available at http://genomes.urv.es/CAIcal/E-CAI, is a web-application that calculates an expected value of CAI for a set of query sequences by generating random sequences with G+C and amino acid content similar to those of the input. An executable file, a tutorial, a Frequently Asked Questions (FAQ) section and several examples are also available. To exemplify the use of the E-CAI server, we have analysed the codon adaptation of human mitochondrial genes that codify a subunit of the mitochondrial respiratory chain (excluding those genes that lack a prokaryotic orthologue) and are encoded in the nuclear genome. It is assumed that these genes were transferred from the proto-mitochondrial to the nuclear genome and that its codon usage was then ameliorated.

Conclusion
The E-CAI server provides a direct threshold value for discerning whether the differences in CAI are statistically significant or whether they are merely artifacts that arise from internal biases in the G+C composition and/or amino acid composition of the query sequences.
Bunched, the Drosophilahomolog of the mammalian tumor suppressor TSC-22, promotes cellular growth
Authors: Gluderer Silvia , Oldham Sean , Rintelen Felix , Sulzer Andrea , Schütt Corina , Wu Xiaodong , Raftery Laurel A , Hafen Ernst , Stocker Hugo 
Published: January 2008

Abstract

Background
Transforming Growth Factor-β1 stimulated clone-22 (TSC-22) is assumed to act as a negative growth regulator and tumor suppressor. TSC-22 belongs to a family of putative transcription factors encoded by four distinct loci in mammals. Possible redundancy among the members of the TSC-22/Dip/Bun protein family complicates a genetic analysis. In Drosophila, all proteins homologous to the TSC-22/Dip/Bun family members are derived from a single locus called bunched (bun).

Results
We have identified bun in an unbiased genetic screen for growth regulators in Drosophila. Rather unexpectedly, bun mutations result in a growth deficit. Under standard conditions, only the long protein isoform BunA – but not the short isoforms BunB and BunC – is essential and affects growth. Whereas reducing bunA function diminishes cell number and cell size, overexpression of the short isoforms BunB and BunC antagonizes bunA function.

Conclusion
Our findings establish a growth-promoting function of Drosophila BunA. Since the published studies on mammalian systems have largely neglected the long TSC-22 protein version, we hypothesize that the long TSC-22 protein is a functional homolog of BunA in growth regulation, and that it is antagonized by the short TSC-22 protein.
The cyanobacterial endosymbiont of the unicellular algae Rhopalodia gibba shows reductive genome evolution
Authors: Kneip Christoph , Voβ Christine , Lockhart Peter J , Maier Uwe G 
Published: January 2008

Abstract

Background
Bacteria occur in facultative association and intracellular symbiosis with a diversity of eukaryotic hosts. Recently, we have helped to characterise an intracellular nitrogen fixing bacterium, the so-called spheroid body, located within the diatom Rhopalodia gibba. Spheroid bodies are of cyanobacterial origin and exhibit features that suggest physiological adaptation to their intracellular life style. To investigate the genome modifications that have accompanied the process of endosymbiosis, here we compare gene structure, content and organisation in spheroid body and cyanobacterial genomes.

Results
Comparison of the spheroid body's genome sequence with corresponding regions of near free-living relatives indicates that multiple modifications have occurred in the endosymbiont's genome. These include localised changes that have led to elimination of some genes. This gene loss has been accompanied either by deletion of the respective DNA region or replacement with non-coding DNA that is AT rich in composition. In addition, genome modifications have led to the fusion and truncation of genes. We also report that in the spheroid body's genome there is an accumulation of deleterious mutations in genes for cell wall biosynthesis and processes controlled by transposases. Interestingly, the formation of pseudogenes in the spheroid body has occurred in the presence of intact, and presumably functional, rec A and rec F genes. This is in contrast to the situation in most investigated obligate intracellular bacterium-eukaryote symbioses, where at least either rec A or rec F has been eliminated.

Conclusion
Our analyses suggest highly specific targeting/loss of individual genes during the process of genome reduction and establishment of a cyanobacterial endosymbiont inside a eukaryotic cell. Our findings confirm, at the genome level, earlier speculation on the obligate intracellular status of the spheroid body in Rhopalodia gibba. This association is the first example of an obligate cyanobacterial symbiosis involving nitrogen fixation for which genomic data are available. It represents a new model system to study molecular adaptations of genome evolution that accompany a switch from free-living to intracellular existence.
Microsatellite-based phylogeny of Indian domestic goats
Authors: Rout Pramod K , Joshi Manjunath B , Mandal Ajoy , Laloe D , Singh Lalji , Thangaraj Kumarasamy 
Published: January 2008

AbstractBackgroundThe domestic goat is one of the important livestock species of India. In the present study we assess genetic diversity of Indian goats using 17 microsatellite markers. Breeds were sampled from their natural habitat, covering different agroclimatic zones.ResultsThe mean number of alleles per locus (NA) ranged from 8.1 in Barbari to 9.7 in Jakhrana goats. The mean expected heterozygosity (He) ranged from 0.739 in Barbari to 0.783 in Jakhrana goats. Deviations from Hardy-Weinberg Equilibrium (HWE) were statistically significant (P < 0.05) for 5 loci breed combinations. The DAmeasure of genetic distance between pairs of breeds indicated that the lowest distance was between Marwari and Sirohi (0.135). The highest distance was between Pashmina and Black Bengal. An analysis of molecular variance indicated that 6.59% of variance exists among the Indian goat breeds. Both a phylogenetic tree and Principal Component Analysis showed the distribution of breeds in two major clusters with respect to their geographic distribution.ConclusionOur study concludes that Indian goat populations can be classified into distinct genetic groups or breeds based on the microsatellites as well as mtDNA information.
Amplification biases: possible differences among deviating gene expressions
Authors: Degrelle Séverine A , Hennequet-Antier Christelle , Chiapello Hélène , Piot-Kaminski Karine , Piumi Francois , Robin Stéphane , Renard Jean-Paul , Hue Isabelle 
Published: January 2008

Abstract

Background
Gene expression profiling has become a tool of choice to study pathological or developmental questions but in most cases the material is scarce and requires sample amplification. Two main procedures have been used: in vitro transcription (IVT) and polymerase chain reaction (PCR), the former known as linear and the latter as exponential. Previous reports identified enzymatic pitfalls in PCR and IVT protocols; however the possible differences between the sequences affected by these amplification defaults were only rarely explored.

Results
Screening a bovine cDNA array dedicated to embryonic stages with embryonic (n = 3) and somatic tissues (n = 2), we proceeded to moderate amplifications starting from 1 μg of total RNA (global PCR or IVT one round). Whatever the tissue, 16% of the probes were involved in deviating gene expressions due to amplification defaults. These distortions were likely due to the molecular features of the affected sequences (position within a gene, GC content, hairpin number) but also to the relative abundance of these transcripts within the tissues. These deviating genes mainly encoded housekeeping genes from physiological or cellular processes (70%) and constituted 2 subsets which did not overlap (molecular features, signal intensities, gene ID). However, the differential expressions identified between embryonic stages were both reliable (minor intersect with biased expressions) and relevant (biologically validated). In addition, the relative expression levels of those genes were biologically similar between amplified and unamplified samples.

Conclusion
Conversely to the most recent reports which challenged the use of intense amplification procedures on minute amounts of RNA, we chose moderate PCR and IVT amplifications for our gene profiling study. Conclusively, it appeared that systematic biases arose even with moderate amplification procedures, independently of (i) the sample used: brain, ovary or embryos, (ii) the enzymatic properties initially inferred (exponential or linear) and (iii) the preliminary optimization of the protocols. Moreover the use of an in-house developed array, small-sized but well suited to the tissues we worked with, was of real interest for the search of differential expressions.
Relationship between mRNA secondary structure and sequence variability in Chloroplast genes: possible life history implications
Authors: Krishnan Neeraja M , Seligmann Hervé , Rao Basuthkar J 
Published: January 2008

Abstract

Background
Synonymous sites are freer to vary because of redundancy in genetic code. Messenger RNA secondary structure restricts this freedom, as revealed by previous findings in mitochondrial genes that mutations at third codon position nucleotides in helices are more selected against than those in loops. This motivated us to explore the constraints imposed by mRNA secondary structure on evolutionary variability at all codon positions in general, in chloroplast systems.

Results
We found that the evolutionary variability and intrinsic secondary structure stability of these sequences share an inverse relationship. Simulations of most likely single nucleotide evolution in Psilotum nudum and Nephroselmis olivacea mRNAs, indicate that helix-forming propensities of mutated mRNAs are greater than those of the natural mRNAs for short sequences and vice-versa for long sequences. Moreover, helix-forming propensity estimated by the percentage of total mRNA in helices increases gradually with mRNA length, saturating beyond 1000 nucleotides. Protection levels of functionally important sites vary across plants and proteins: r-strategists minimize mutation costs in large genes; K-strategists do the opposite.

Conclusion
Mrna length presumably predisposes shorter mRNAs to evolve under different constraints than longer mRNAs. The positive correlation between secondary structure protection and functional importance of sites suggests that some sites might be conserved due to packing-protection constraints at the nucleic acid level in addition to protein level constraints. Consequently, nucleic acid secondary structure a priori biases mutations. The converse (exposure of conserved sites) apparently occurs in a smaller number of cases, indicating a different evolutionary adaptive strategy in these plants. The differences between the protection levels of functionally important sites for r- and K- strategists reflect their respective molecular adaptive strategies. These converge with increasing domestication levels of K-strategists, perhaps because domestication increases reproductive output.
Ability of Lactobacillus fermentum to overcome host α-galactosidase deficiency, as evidenced by reduction of hydrogen excretion in rats consuming soya α-galacto-oligosaccharides
Authors: LeBlanc Jean Guy , Ledue-Clier Florence , Bensaada Martine , de Giori Graciela Savoy , Guerekobaya Theodora , Sesma Fernando , Juillard Vincent , Rabot Sylvie , Piard Jean-Christophe 
Published: January 2008

AbstractBackgroundSoya and its derivatives represent nutritionally high quality food products whose major drawback is their high content of α-galacto-oligosaccharides. These are not digested in the small intestine due to the natural absence of tissular α-galactosidase in mammals. The passage of these carbohydrates to the large intestine makes them available for fermentation by gas-producing bacteria leading to intestinal flatulence. The aim of the work reported here was to assess the ability of α-galactosidase-producing lactobacilli to improve the digestibility of α-galacto-oligosaccharidesin situ.ResultsGnotobiotic rats were orally fed with soy milk and placed in respiratory chambers designed to monitor fermentative gas excretion. The validity of the animal model was first checked using gnotobiotic rats monoassociated with aClostridium butyricumhydrogen (H2)-producing strain. Ingestion of native soy milk by these rats caused significant H2emission while ingestion of α-galacto-oligosaccharide-free soy milk did not, thus validating the experimental system. When native soy milk was fermented using the α-galactosidase-producingLactobacillus fermentumCRL722 strain, the resulting product failed to induce H2emission in rats thus validating the bacterial model. WhenL. fermentumCRL722 was coadministered with native soy milk, a significant reduction (50 %,P= 0.019) in H2emission was observed, showing that α-galactosidase fromL. fermentumCRL722 remained activein situ, in the gastrointestinal tract of rats monoassociated withC. butyricum. In human-microbiota associated rats,L. fermentumCRL722 also induced a significant reduction of H2emission (70 %,P= 0.004).ConclusionThese results strongly suggest thatL. fermentumα-galactosidase is able to partially alleviate α-galactosidase deficiency in rats. This offers interesting perspectives in various applications in which lactic acid bacteria could be used as a vector for delivery of digestive enzymes in man and animals.
In vitro activity of telithromycin against Haemophilus influenzae at epithelial lining fluid concentrations
Authors: De Vecchi Elena , Nicola Lucia , Larosa Monica , Drago Lorenzo 
Published: January 2008

Abstract

Background

Haemophilus influenzae is one of the main aetiological agents of community-acquired respiratory tract infections. The primary aim of this study was to evaluate the antibacterial activity of telithromycin against H. influenzae clinical isolates showing different pattern of resistance in comparison with azithromycin and clarithromycin at 1/4 ×, 1/2 ×, 1 ×, 2 ×, 4 × minimum inhibitory concentration (MIC) and to peak concentrations in epithelial lining fluid (ELF). The secondary aim was to determine the influence of CO2 enriched atmosphere on bacterial susceptibility.

Results
Telithromycin showed high activity against H. influenzae, including strains susceptible to β-lactams (n = 200), β-lactamase producer (n = 50) and β-lactamase negative ampicillin resistant (BLNAR) (n = 10), with MIC from ≤0.03 to 4 mg/L, and MIC50/MIC90 of 1/2 mg/L with susceptibility rate of 100%, and minimum bactericidal concentrations (MBC) from 2 to 4-fold higher than the MIC. Azithromycin was the most active tested macrolide (range: 0.25 – 4 mg/L; MIC50/MIC90: 1/2 mg/L), comparable to telithromycin, while clarithromycin showed the highest MICs and MBCs (range: 0.25 – 8 mg/L; MIC50/MIC90: 2/8 mg/L). In time-kill studies, telithromycin showed a bactericidal activity at the higher concentrations (4 – 2 × MIC and ELF) against all the strains, being complete after 12 – 24 hours from drug exposition. At MIC concentrations, at ambient air, bactericidal activity of telithromycin and azithromycin was quite similar at 12 hours, and better than that of clarithromycin. Besides, telithromycin and clarithromycin at ELF concentrations were bactericidal after 12 hours of incubation for most strains, while 24 hours were needed to azithromycin to be bactericidal. Incubation in CO2 significantly influenced the MICs and MBCs, and only slightly the in vitro killing curves.

Conclusion
Telithromycin showed an in-vitro potency against H. influenzae comparable to azithromycin, with an in-vitro killing rate more rapid and superior to clarithromycin at 2X-MIC against β-lactamase producers and BLNAR strains, and to azithromycin at ELF concentrations against β-lactamase negative strains. Against all strains, MICs and MBCs were lower in the absence of CO2 for the tested antibiotics, showing an adverse effect of incubation in a CO2 environment. The in-vitro potency together with the tissue concentrations of the antimicrobial, should be considered in predicting efficacy.
Frequent expression loss of Inter-alpha-trypsin inhibitor heavy chain (ITIH) genes in multiple human solid tumors: A systematic expression analysis
Authors: Hamm Alexander , Veeck Juergen , Bektas Nuran , Wild Peter J , Hartmann Arndt , Heindrichs Uwe , Kristiansen Glen , Werbowetski-Ogilvie Tamra , Del Maestro Rolando , Knuechel Ruth , Dahl Edgar 
Published: January 2008

AbstractBackgroundThe inter-alpha-trypsin inhibitors (ITI) are a family of plasma protease inhibitors, assembled from a light chain – bikunin, encoded byAMBP– and five homologous heavy chains (encoded byITIH1,ITIH2,ITIH3,ITIH4, andITIH5), contributing to extracellular matrix stability by covalent linkage to hyaluronan. So far, ITIH molecules have been shown to play a particularly important role in inflammation and carcinogenesis.MethodsWe systematically investigated differential gene expression of theITIHgene family, as well asAMBPand the interacting partnerTNFAIP6in 13 different human tumor entities (of breast, endometrium, ovary, cervix, stomach, small intestine, colon, rectum, lung, thyroid, prostate, kidney, and pancreas) using cDNA dot blot analysis (Cancer Profiling Array, CPA), semiquantitative RT-PCR and immunohistochemistry.ResultsWe found thatITIHgenes are clearly downregulated in multiple human solid tumors, including breast, colon and lung cancer. Thus,ITIHgenes may represent a family of putative tumor suppressor genes that should be analyzed in greater detail in the future. For an initial detailed analysis we choseITIH2expression in human breast cancer. Loss ofITIH2expression in 70% of cases (n = 50, CPA) could be confirmed by real-time PCR in an additional set of breast cancers (n = 36). Next we studied ITIH2 expression on the protein level by analyzing a comprehensive tissue micro array including 185 invasive breast cancer specimens. We found a strong correlation (p < 0.001) between ITIH2 expression and estrogen receptor (ER) expression indicating that ER may be involved in the regulation of this ECM molecule.ConclusionAltogether, this is the first systematic analysis on the differential expression ofITIHgenes in human cancer, showing frequent downregulation that may be associated with initiation and/or progression of these malignancies.
Markers of subtypes in inflammatory breast cancer studied by immunohistochemistry: Prominent expression of P-cadherin
Authors: Ben Hamida Azza , Labidi Intidhar S , Mrad Karima , Charafe-Jauffret Emmanuelle , Ben Arab Saïda , Esterni Benjamin , Xerri Luc , Viens Patrice , Bertucci François , Birnbaum Daniel , Jacquemier Jocelyne 
Published: January 2008

AbstractBackgroundInflammatory breast cancer (IBC) is a distinct and aggressive form of locally-advanced breast cancer with high metastatic potential. In Tunisia, IBC is associated with a high death rate. Among the major molecular subtypes, basal breast carcinomas are poorly differentiated, have metastatic potential and poor prognosis, but respond relatively well to chemotherapy. The aim of this study was to determine the distribution of molecular subtypes in IBC and identify factors that may explain the poor prognosis of IBC.MethodsTo determine breast cancer subtypes we studied by immunohistochemistry the expression of 12 proteins in a series of 91 Tunisian IBC and 541 non-IBC deposited in tissue microarrays.ResultsWe considered infiltrating ductal cases only. We found 33.8% of basal cases in IBC vs 15.9% in non-IBC (p < 0.001), 33.3% of ERBB2-overexpressing cases in IBC vs 14.5% in non-IBC (p < 0.001), and 29.3% of luminal cases in IBC vs 59.9% in non-IBC (p < 0.001). The most differentially-expressed protein between IBCs and non-IBCs was P-cadherin. P-cadherin expression was found in 75.9% of all IBC vs 48.2% of all non-IBC (p < 0.001), 95% of IBC vs 69% of non-IBC (p = 0.02) in basal cases, and 82% of IBC vs 43% of non-IBC (p < 0.001) in luminal cases. Logistic regression determined that the most discriminating markers between IBCs and non-IBCs were P-cadherin (OR = 4.9, p = 0.0019) MIB1 (OR = 3.6, p = 0.001), CK14 (OR = 2.7, p = 0.02), and ERBB2 (OR = 2.3, p = 0.06).ConclusionTunisian IBCs are characterized by frequent basal and ERBB2 phenotypes. Surprisingly, luminal IBC also express the basal marker P-cadherin. This profile suggests a specificity that needs further investigation.