bluuebunny/crossref_metadata_2025_split huggingface dataset:
Expression profiles of cIRF6, cLHX6 and cLHX7in the facial primordia suggest specific roles during primary palatogenesis
Authors: Washbourne Belinda J , Cox Timothy C 
Published: April 2006

Abstract
Background
The LIM-homeodomain transcription factors LHX7 and LHX6 have been implicated in palatogenesis in mice and thus may also contribute to the incidence of isolated palatal clefts and/or clefts of the lip and primary palate (CL/P) in humans. Causative mutations in the transcription factor IRF6 have also been identified in two allelic CL/P syndromes and common polymorphisms in the same gene are significantly associated with non-syndromal CL/P in different populations.

Results
Here we report the isolation of chick orthologues of LHX7, LHX6 and IRF6 and the first characterisation of their profiles of expression during morphogenesis of the midface with emphasis on the period around formation of the primary palate. LHX7 and LHX6 expression was restricted to the ectomesenchyme immediately underlying the ectoderm of the maxillary and mandibular primordia as well as to the lateral globular projections of the medial nasal process, again underlying the pre-fusion primary palatal epithelia. In contrast, IRF6 expression was restricted to surface epithelia, with elevated levels around the frontonasal process, the maxillary primordia, and the nasal pits. Elsewhere, high expression was also evident in the egg tooth primordium and in the apical ectodermal ridge of the developing limbs.

Conclusion
The restricted expression of both LHX genes and IRF6 in the facial primordia suggests roles for these gene products in promoting directed outgrowth and fusion of the primary palate. The manipulability, minimal cost and susceptibility of chicks to CL/P will enable more detailed investigations into how perturbations of IRF6, LHX6 and LHX7 contribute to common orofacial clefts.
Multiple lineage specific expansions within the guanylyl cyclase gene family
Authors: Fitzpatrick David A , O'Halloran Damien M , Burnell Ann M 
Published: April 2006

Abstract

Background
Guanylyl cyclases (GCs) are responsible for the production of the secondary messenger cyclic guanosine monophosphate, which plays important roles in a variety of physiological responses such as vision, olfaction, muscle contraction, homeostatic regulation, cardiovascular and nervous function. There are two types of GCs in animals, soluble (sGCs) which are found ubiquitously in cell cytoplasm, and receptor (rGC) forms which span cell membranes. The complete genomes of several vertebrate and invertebrate species are now available. These data provide a platform to investigate the evolution of GCs across a diverse range of animal phyla.

Results
In this analysis we located GC genes from a broad spectrum of vertebrate and invertebrate animals and reconstructed molecular phylogenies for both sGC and rGC proteins. The most notable features of the resulting phylogenies are the number of lineage specific rGC and sGC expansions that have occurred during metazoan evolution. Among these expansions is a large nematode specific rGC clade comprising 21 genes in C. elegans alone; a vertebrate specific expansion in the natriuretic receptors GC-A and GC-B; a vertebrate specific expansion in the guanylyl GC-C receptors, an echinoderm specific expansion in the sperm rGC genes and a nematode specific sGC clade. Our phylogenetic reconstruction also shows the existence of a basal group of nitric oxide (NO) insensitive insect and nematode sGCs which are regulated by O2. This suggests that the primordial eukaryotes probably utilized sGC as an O2 sensor, with the ligand specificity of sGC later switching to NO which provides a very effective local cell-to-cell signalling system. Phylogenetic analysis of the sGC and bacterial heme nitric oxide/oxygen binding protein domain supports the hypothesis that this domain originated from a cyanobacterial source.

Conclusion
The most salient feature of our phylogenies is the number of lineage specific expansions, which have occurred within the GC gene family during metazoan evolution. Our phylogenetic analyses reveal that the rGC and sGC multi-domain proteins evolved early in eumetazoan evolution. Subsequent gene duplications, tissue specific expression patterns and lineage specific expansions resulted in the evolution of new networks of interaction and new biological functions associated with the maintenance of organismal complexity and homeostasis.
Population genetic estimation of the loss of genetic diversity during horizontal transmission of HIV-1
Authors: Edwards Charles TT , Holmes Edward C , Wilson Daniel J , Viscidi Raphael P , Abrams Elaine J , Phillips Rodney E , Drummond Alexei J 
Published: April 2006

AbstractBackgroundGenetic diversity of the human immunodeficiency virus type 1 (HIV-1) population within an individual is lost during transmission to a new host. The demography of transmission is an important determinant of evolutionary dynamics, particularly the relative impact of natural selection and genetic drift immediately following HIV-1 infection. Despite this, the magnitude of this population bottleneck is unclear.ResultsWe use coalescent methods to quantify the bottleneck in a single case of homosexual transmission and find that over 99% of theenvandgagdiversity present in the donor is lost. This was consistent with the diversity present at seroconversion in nine other horizontally infected individuals. Furthermore, we estimated viral diversity at birth in 27 infants infected through vertical transmission and found there to be no difference between the two modes of transmission.ConclusionAssuming the bottleneck at transmission is selectively neutral, such a severe reduction in genetic diversity has important implications for adaptation in HIV-1, since beneficial mutations have a reduced chance of transmission.
Assessment of methods for amino acid matrix selection and their use on empirical data shows that ad hoc assumptions for choice of matrix are not justified
Authors: Keane Thomas M , Creevey Christopher J , Pentony Melissa M , Naughton Thomas J , Mclnerney James O 
Published: April 2006

Abstract

Background
In recent years, model based approaches such as maximum likelihood have become the methods of choice for constructing phylogenies. A number of authors have shown the importance of using adequate substitution models in order to produce accurate phylogenies. In the past, many empirical models of amino acid substitution have been derived using a variety of different methods and protein datasets. These matrices are normally used as surrogates, rather than deriving the maximum likelihood model from the dataset being examined. With few exceptions, selection between alternative matrices has been carried out in an ad hoc manner.

Results
We start by highlighting the potential dangers of arbitrarily choosing protein models by demonstrating an empirical example where a single alignment can produce two topologically different and strongly supported phylogenies using two different arbitrarily-chosen amino acid substitution models. We demonstrate that in simple simulations, statistical methods of model selection are indeed robust and likely to be useful for protein model selection. We have investigated patterns of amino acid substitution among homologous sequences from the three Domains of life and our results show that no single amino acid matrix is optimal for any of the datasets. Perhaps most interestingly, we demonstrate that for two large datasets derived from the proteobacteria and archaea, one of the most favored models in both datasets is a model that was originally derived from retroviral Pol proteins.

Conclusion
This demonstrates that choosing protein models based on their source or method of construction may not be appropriate.
Spontaneous rescue from cystic fibrosis in a mouse model
Authors: Charizopoulou Nikoletta , Wilke Martina , Dorsch Martina , Bot Alice , Jorna Huub , Jansen Silke , Stanke Frauke , Hedrich Hans J , de Jonge Hugo R , Tümmler Burkhard 
Published: April 2006

Abstract

Background
From the original Cftr

TgH(neoim)Hgu
mutant mouse model with a divergent genetic background (129P2, C57BL/6, MF1) we have generated two inbred Cftr

TgH(neoim)Hgu
mutant strains named CF/1-Cftr

TgH(neoim)Hgu
and CF/3-Cftr

TgH(neoim)Hgu
, which are fertile and show normal growth and lifespan. Initial genome wide scan analysis with microsatellite markers indicated that the two inbred strains differed on the genetic level. In order to further investigate whether these genetic differences have an impact on the disease phenotype of cystic fibrosis we characterised the phenotype of the two inbred strains.

Results
Reduced amounts, compared to wild type control animals, of correctly spliced Cftr mRNA were detected in the nasal epithelia, lungs and the intestine of both inbred Cftr

TgH(neoim)Hgu
strains, with higher residual amount observed for CF/1-Cftr

TgH(neoim)Hgu
than CF/3-Cftr

TgH(neoim)Hgu
for every investigated tissue. Accordingly the amounts of wild type Cftr protein in the intestine were 9% for CF/1-Cftr

TgH(neoim)Hgu
and 4% for CF/3-Cftr

TgH(neoim)Hgu
. Unlike the apparent strain and/or tissue specific regulation of Cftr mRNA splicing, short circuit current measurements in the respiratory and intestinal epithelium revealed that both strains have ameliorated the basic defect of cystic fibrosis with a presentation of a normal electrophysiology in both tissues.

Conclusion
Unlike the outbred Cftr

TgH(neoim)Hgu
insertional mouse model, which displayed the electrophysiological defect in the gastrointestinal and respiratory tracts characteristic of cystic fibrosis, both inbred Cftr

TgH(neoim)Hgu
strains have ameliorated the electrophysiological defect. On the basis of these findings both CF/1-Cftr

TgH(neoim)Hgu
and CF/3-Cftr

TgH(neoim)Hgu
offer an excellent model whereby determination of the minimal levels of protein required for the restoration of the basic defect of cystic fibrosis can be studied, along with the modulating factors which may affect this outcome.
Comparison of the latest commercial short and long oligonucleotide microarray technologies
Authors: de Reyniès Aurélien , Geromin Daniela , Cayuela Jean-Michel , Petel Fabien , Dessen Philippe , Sigaux François , Rickman David S 
Published: April 2006

AbstractBackgroundWe compared the relative precision and accuracy of expression measurements obtained from three different state-of-the-art commercial short and long-oligonucleotide microarray platforms (Affymetrix GeneChip™, GE Healthcare CodeLink™ and Agilent Technologies). The design of the comparison was chosen to judge each platform in the context of a multi-project program.ResultsAll wet-lab experiments and raw data acquisitions were performed independently by each commercial platform. Intra-platform reproducibility was assessed using measurements from all available targets. Inter-platform comparisons of relative signal intensities were based on a common and non-redundant set of roughly 3,400 targets chosen for their unique correspondence toward a single transcript. Despite many examples of strong similarities we found several areas of discrepancy between the different platforms.ConclusionWe found a higher level of reproducibility from one-color based microarrays (Affymetrix and CodeLink) compared to the two-color arrays from Agilent. Overall, Affymetrix data had a slightly higher level of concordance with sample-matched real-time quantitative reverse-transcriptase polymerase chain reaction (QRT-PCR) data particularly for detecting small changes in gene expression levels.
Linkage disequilibrium interval mapping of quantitative trait loci
Authors: Boitard Simon , Abdallah Jihad , de Rochambeau Hubert , Cierco-Ayrolles Christine , Mangin Brigitte 
Published: April 2006

AbstractBackgroundFor many years gene mapping studies have been performed through linkage analyses based on pedigree data. Recently, linkage disequilibrium methods based on unrelated individuals have been advocated as powerful tools to refine estimates of gene location. Many strategies have been proposed to deal with simply inherited disease traits. However, locating quantitative trait loci is statistically more challenging and considerable research is needed to provide robust and computationally efficient methods.ResultsUnder a three-locus Wright-Fisher model, we derived approximate expressions for the expected haplotype frequencies in a population. We considered haplotypes comprising one trait locus and two flanking markers. Using these theoretical expressions, we built a likelihood-maximization method, called HAPim, for estimating the location of a quantitative trait locus. For each postulated position, the method only requires information from the two flanking markers. Over a wide range of simulation scenarios it was found to be more accurate than a two-marker composite likelihood method. It also performed as well as identity by descent methods, whilst being valuable in a wider range of populations.ConclusionOur method makes efficient use of marker information, and can be valuable for fine mapping purposes. Its performance is increased if multiallelic markers are available. Several improvements can be developed to account for more complex evolution scenarios or provide robust confidence intervals for the location estimates.
Developmental disturbances in early life stage mortality (M74) of Baltic salmon fry as studied by changes in gene expression
Authors: Vuori Kristiina AM , Koskinen Heikki , Krasnov Aleksei , Koivumäki Paula , Afanasyev Sergey , Vuorinen Pekka J , Nikinmaa Mikko 
Published: April 2006

Abstract

Background
We have studied alterations of gene expression associated with naturally-occurring early life stage mortality (M74) in Baltic salmon using a cDNA microarray and real time PCR. M74-affected fry have several typical neurological, cardiovascular and pathological symptoms. They are also characterized by low thiamine content and show signs of oxidative stress.

Results
Affected fry can be divided into three major groups with early, intermediate or late onset of mortality. If mortality starts during the first third of the yolk-sac stage, virtually all the responses are compatible with stress, which rapidly leads to the common terminal responses. If death occurs during the second third of the yolk sac stage, the terminal stage is preceded by a decrease in globin gene expression, which leads to internal hypoxia when the animals grow and shift from skin- to gill-breathing. Fry will eventually proceed to the terminal responses. The group developing M74 most slowly appears to compensate for reduced oxygen delivery by downregulation of metabolism, and hence some fry can escape death.

Conclusion
Our study is the first demonstration of diverse transcriptional responses to a naturally-occurring developmental disturbance. Since many of the genes differentially expressed in M74-fry are evolutionarily conserved, the M74 of Baltic salmon can serve as a model for developmental disturbances and environmental stress responses in vertebrates in general.
Trypanosoma cruzi mitochondrial maxicircles display species- and strain-specific variation and a conserved element in the non-coding region
Authors: Westenberger Scott J , Cerqueira Gustavo C , El-Sayed Najib M , Zingales Bianca , Campbell David A , Sturm Nancy R 
Published: April 2006

Abstract

Background
The mitochondrial DNA of kinetoplastid flagellates is distinctive in the eukaryotic world due to its massive size, complex form and large sequence content. Comprised of catenated maxicircles that contain rRNA and protein-coding genes and thousands of heterogeneous minicircles encoding small guide RNAs, the kinetoplast network has evolved along with an extreme form of mRNA processing in the form of uridine insertion and deletion RNA editing. Many maxicircle-encoded mRNAs cannot be translated without this post-transcriptional sequence modification.

Results
We present the complete sequence and annotation of the Trypanosoma cruzi maxicircles for the CL Brener and Esmeraldo strains. Gene order is syntenic with Trypanosoma brucei and Leishmania tarentolae maxicircles. The non-coding components have strain-specific repetitive regions and a variable region that is unique for each strain with the exception of a conserved sequence element that may serve as an origin of replication, but shows no sequence identity with L. tarentolae or T. brucei. Alternative assemblies of the variable region demonstrate intra-strain heterogeneity of the maxicircle population. The extent of mRNA editing required for particular genes approximates that seen in T. brucei. Extensively edited genes were more divergent among the genera than non-edited and rRNA genes. Esmeraldo contains a unique 236-bp deletion that removes the 5'-ends of ND4 and CR4 and the intergenic region. Esmeraldo shows additional insertions and deletions outside of areas edited in other species in ND5, MURF1, and MURF2, while CL Brener has a distinct insertion in MURF2.

Conclusion
The CL Brener and Esmeraldo maxicircles represent two of three previously defined maxicircle clades and promise utility as taxonomic markers. Restoration of the disrupted reading frames might be accomplished by strain-specific RNA editing. Elements in the non-coding region may be important for replication, transcription, and anchoring of the maxicircle within the kinetoplast network.
DNA deformability changes of single base pair mutants within CDE binding sites in S. Cerevisiae centromere DNA correlate with measured chromosomal loss rates and CDE binding site symmetries
Authors: Hennemuth Brad , Marx Kenneth A 
Published: April 2006

Abstract

Background
The centromeres in yeast (S. cerevisiae) are organized by short DNA sequences (125 bp) on each chromosome consisting of 2 conserved elements: CDEI and CDEIII spaced by a CDEII region. CDEI and CDEIII are critical sequence specific protein binding sites necessary for correct centromere formation and following assembly with proteins, are positioned near each other on a specialized nucleosome. Hegemann et al. BioEssays 1993, 15: 451–460 reported single base DNA mutants within the critical CDEI and CDEIII binding sites on the centromere of chromosome 6 and quantitated centromere loss of function, which they measured as loss rates for the different chromosome 6 mutants during cell division. Olson et al. Proc Natl Acad Sci USA 1998, 95: 11163–11168 reported the use of protein-DNA crystallography data to produce a DNA dinucleotide protein deformability energetic scale (PD-scale) that describes local DNA deformability by sequence specific binding proteins. We have used the PD-scale to investigate the DNA sequence dependence of the yeast chromosome 6 mutants' loss rate data. Each single base mutant changes 2 PD-scale values at that changed base position relative to the wild type. In this study, we have utilized these mutants to demonstrate a correlation between the change in DNA deformability of the CDEI and CDEIII core sites and the overall experimentally measured chromosome loss rates of the chromosome 6 mutants.

Results
In the CDE I and CDEIII core binding regions an increase in the magnitude of change in deformability of chromosome 6 single base mutants with respect to the wild type correlates to an increase in the measured chromosome loss rate. These correlations were found to be significant relative to 105 Monte Carlo randomizations of the dinucleotide PD-scale applied to the same calculation. A net loss of deformability also tends to increase the loss rate. Binding site position specific, 4 data-point correlations were also created using the wild type sequence and the 3 associated alternate base mutants at each binding site position. These position specific slope magnitudes, or sensitivities, correlated with and reflected the underlying position symmetry of the DNA binding sequences.

Conclusion
These results suggest the utility of correlating quantitative aspects of sequence specific protein-DNA complex single base mutants with changes in the easily calculated PD-deformability scale of the individual DNA sequence mutants. Using this PD approach, it may be possible in the future to understand the magnitude of biological or energetic functional effects of specific DNA sequence mutants within DNA-protein complexes in terms of their effect on DNA deformability.
A potential role of alternative splicing in the regulation of the transcriptional activity of human GLI2 in gonadal tissues
Authors: Speek Mart , Njunkova Olga , Pata Illar , Valdre Eola , Kogerman Priit 
Published: April 2006

Abstract

Background
Mammalian Gli proteins are important transcription factors involved in the regulation of Sonic hedgehog signal transduction pathway. Association of Gli2 with mammalian development and human disease led us to study the structure and expression of the human GLI2.

Results
We show that the region encoding GLI2 repressor domain is subject to alternative splicing in the gonadal tissues and different cell lines. Two major alternatively spliced forms of GLI2 mRNA arise from skipping exon 3 (GLI2 Δ3) or exons 4 and 5 (GLI2 Δ4–5). Both forms contain premature translational stop codons in the GLI2 open reading frame (ORF) starting from exon 2. Translation of GLI2 Δ3 and GLI2 Δ4–5 in vitro, initiated from downstream AUG codons, produced N-terminally truncated proteins. In Gli-dependent transactivation assay, expression of GLI2 Δ3 induced activation of the reporter gene similar to that of the full-length construct (GLI2 fl) containing complete ORF. However, expression of the GLI2 Δ4–5 resulted in about 10-fold increase in activation, suggesting that deletion of the major part of repressor domain was responsible for the enhanced activation of GLI2 protein.

Conclusion
Our data suggest that in addition to proteolytic processing, alternative splicing may be another important regulatory mechanism for the modulation of repressor and activator properties of GLI2 protein.