bluuebunny/crossref_metadata_2025_split huggingface dataset:
Density enhanced phosphatase-1 down-regulates urokinase receptor surface expression in confluent endothelial cells
Authors: Brunner Patrick M. , Heier Patricia C. , Mihaly-Bison Judit , Priglinger Ute , Binder Bernd R. , Prager Gerald W. 
Published: February 2011

AbstractVEGF165, the major angiogenic growth factor, is known to activate various steps in proangiogenic endothelial cell behavior, such as endothelial cell migration and invasion, or endothelial cell survival. Thereby, the urokinase-type plasminogen activator (uPA) system has been shown to play an essential role not only by its proteolytic capacities, but also by induction of intracellular signal transduction. Therefore, expression of its cell surface receptor uPAR is thought to be an essential regulatory mechanism in angiogenesis. We found that uPAR expression on the surface of confluent endothelial cells was down-regulated compared with subconfluent proliferating endothelial cells. Regulation of uPAR expression was most probably affected by extracellular signal-regulated kinase 1/2 (ERK1/2) activation, a downstream signaling event of the VEGF/VEGF-receptor system. Consistently, the receptor-like protein tyrosine phosphatase DEP-1 (density enhanced phosphatase-1/CD148), which is abundantly expressed in confluent endothelial cells, inhibited the VEGF-dependent activation of ERK1/2, leading to down-regulation of uPAR expression. Overexpression of active ERK1 rescued the DEP-1 effect on uPAR. That DEP-1 plays a biologic role in angiogenic endothelial cell behavior was demonstrated in endothelial cell migration, proliferation, and capillary-like tube formation assays in vitro.
PRE-1, a cis element sufficient to enhance cone- and rod- specific expression in differentiating zebrafish photoreceptors
Authors: Morrissey Maria E , Shelton Sara , Brockerhoff Susan E , Hurley James B , Kennedy Breandán N 
Published: February 2011

Abstract

Background
Appropriate transcriptional regulation is required for cone photoreceptor development and integrity. To date, only a few cis-regulatory elements that control cone photoreceptor-specific expression have been characterised. The alpha-subunit of cone transducin (TαC) is specifically expressed in cone photoreceptors and is required for colour vision. In order to better understand the molecular genetics controlling the initiation of cone photoreceptor-specific expression in vivo, we have utilised zebrafish to identify cis-regulatory elements in the upstream promoter region of the TαC gene.

Results
A 0.5 kb TαC promoter fragment is sufficient to direct cone-specific expression in transgenic larvae. Within this minimal promoter, we identify photoreceptor regulatory element-1 (PRE-1), a unique 41 bp sequence. PRE-1 specifically binds nuclear factors expressed in ocular tissue. PRE-1 is not required for cone-specific expression directed from a 2.5 kb TαC promoter. However, PRE-1-like sequences, with potential functional redundancy, are located in this 2.5 kb promoter. PRE-1-rho which has the highest sequence and structural homology to PRE-1 is located in the rhodopsin promoter. Surprisingly, PRE-1 and PRE-1-rho are functionally distinct. We demonstrate that PRE-1, but not PRE-1-rho, is sufficient to enhance expression from a heterologous UV cone promoter. PRE-1 is also sufficient to enhance expression from a heterologous rhodopsin promoter without altering its rod photoreceptor specificity. Finally, mutations in consensus E-box and Otx sites prevent PRE-1 from forming complexes with eye nuclear protein and enhancing photoreceptor expression.

Conclusions
PRE-1 is a novel cis-regulatory module that is sufficient to enhance the initiation of photoreceptor-specific gene expression in differentiating rod and cone photoreceptors.
Association and haplotype analysis of candidate genes in five genomic regions linked to sow maternal infanticide in a white Duroc × Erhualian resource population
Authors: Chen Congying , Yang Zhuqing , Li Yanying , Wei Na , Li Pinghua , Guo Yuanmei , Ren Jun , Ding Nengshui , Huang Lusheng 
Published: February 2011

Abstract

Background
Maternal infanticide is an extreme and failed maternal behavior, which is defined as an active attack on piglets using the jaws, resulting in serious or fatal bite wounds. It brings big economic loss to the pig industry and severe problems to piglets' welfare. But little is known about the genetic background of this behavior. Quantitative trait loci (QTL) for maternal infanticide were identified in a White Duroc × Erhualian intercross by a non-parametric linkage analysis (NPL) in our previous study. In this study, associations of 194 microsatellite markers used in NPL analysis with maternal infanticide behavior were further analyzed by transmission-disequilibrium test (TDT). On this basis, seven genes (ESR 2, EAAT 2, BDNF, OXTR, 5-HTR2C, DRD 1 and GABRA 6) at five genomic regions were selected and further analyzed. Associations of single nucleotide polymorphisms (SNPs) and haplotypes in each gene with maternal infanticide behavior were evaluated.

Results
Microsatellite markers on pig chromosome (SSC) 2, 13, 15, and X displayed significance at P < 0.05 by both TDT and NPL. Of the seven candidate genes, three ESR 2 SNPs had nominal evidence for association (P < 0.05). Allele A at EAAT 2 g. 233G > A and allele T at DRD 1 g.1013C > G > T also showed evidence of overtransmission to infanticidal sows. In the overall tests of association of haplotypes, candidate genes of ESR 2, EAAT 2 and DRD 1 achieved overall significance level (P < 0.05). Haplotype [A; A; G], [G; A; G], [A; G; G] and [C; C], respectively, from ESR 2, EAAT 2 and DRD 1 showed higher frequencies to infanticidal sows (P < 0.05). Alleles among haplotypes and SNPs which showed an overtransmission to infanticidal sows were from White Duroc.

Conclusions
From association tests of SNPs and haplotypes, ESR 2, EAAT 2 and DRD 1 showed significant associations with maternal infanticide. This result supported the existence of QTL for maternal infanticide behavior on SSC1, SSC2 and SSC16.
Integration of linkage maps for the Amphidiploid Brassica napus and comparative mapping with Arabidopsis and Brassica rapa
Authors: Wang Jun , Lydiate Derek J , Parkin Isobel AP , Falentin Cyril , Delourme Régine , Carion Pierre WC , King Graham J 
Published: February 2011

AbstractBackgroundThe large number of genetic linkage maps representingBrassicachromosomes constitute a potential platform for studying crop traits and genome evolution withinBrassicaceae. However, the alignment of existing maps remains a major challenge. The integration of these genetic maps will enhance genetic resolution, and provide a means to navigate between sequence-tagged loci, and with contiguous genome sequences as these become available.ResultsWe report the first genome-wide integration ofBrassicamaps based on an automated pipeline which involved collation of genome-wide genotype data for sequence-tagged markers scored on three extensively used amphidiploidBrassica napus(2n = 38) populations. Representative markers were selected from consolidated maps for each population, and skeleton bin maps were generated. The skeleton maps for the three populations were then combined to generate an integrated map for each LG, comparing two different approaches, one encapsulated in JoinMap and the other in MergeMap. The BnaWAIT_01_2010a integrated genetic map was generated using JoinMap, and includes 5,162 genetic markers mapped onto 2,196 loci, with a total genetic length of 1,792 cM. The map density of one locus every 0.82 cM, corresponding to 515 Kbp, increases by at least three-fold the locus and marker density within the original maps. Within theB. napusintegrated map we identified 103 conserved collinearity blocks relative toArabidopsis, including five previously unreported blocks. The BnaWAIT_01_2010a map was used to investigate the integrity and conservation of order proposed for genome sequence scaffolds generated from the constituent A genome ofBrassica rapa.ConclusionsOur results provide a comprehensive genetic integration of theB. napusgenome from a range of sources, which we anticipate will provide valuable information for rapeseed and Canola research.
Responsiveness of genes to manipulation of transcription factors in ES cells is associated with histone modifications and tissue specificity
Authors: Sharov Alexei A , Nishiyama Akira , Piao Yulan , Correa-Cerro Lina S , Amano Tomokazu , Thomas Marshall , Mehta Samir , Ko Minoru SH 
Published: February 2011

Abstract

Background
In addition to determining static states of gene expression (high vs. low), it is important to characterize their dynamic status. For example, genes with H3K27me3 chromatin marks are not only suppressed but also poised for activation. However, the responsiveness of genes to perturbations has never been studied systematically. To distinguish gene responses to specific factors from responsiveness in general, it is necessary to analyze gene expression profiles of cells responding to a large variety of disturbances, and such databases did not exist before.

Results
We estimated the responsiveness of all genes in mouse ES cells using our recently published database on expression change after controlled induction of 53 transcription factors (TFs) and other genes. Responsive genes (N = 4746), which were readily upregulated or downregulated depending on the kind of perturbation, mostly have regulatory functions and a propensity to become tissue-specific upon differentiation. Tissue-specific expression was evaluated on the basis of published (GNF) and our new data for 15 organs and tissues. Non-responsive genes (N = 9562), which did not change their expression much following any perturbation, were enriched in housekeeping functions. We found that TF-responsiveness in ES cells is the best predictor known for tissue-specificity in gene expression. Among genes with CpG islands, high responsiveness is associated with H3K27me3 chromatin marks, and low responsiveness is associated with H3K36me3 chromatin, stronger tri-methylation of H3K4, binding of E2F1, and GABP binding motifs in promoters.

Conclusions
We thus propose the responsiveness of expression to perturbations as a new way to define the dynamic status of genes, which brings new insights into mechanisms of regulation of gene expression and tissue specificity.
Two-step cleavage of hairpin RNA with 5' overhangs by human DICER
Authors: Ando Yoshinari , Maida Yoshiko , Morinaga Ayako , Burroughs Alexander M , Kimura Ryuichiro , Chiba Joe , Suzuki Harukazu , Masutomi Kenkichi , Hayashizaki Yoshihide 
Published: February 2011

AbstractBackgroundDICER is an RNase III family endoribonuclease that processes precursor microRNAs (pre-miRNAs) and long double-stranded RNAs, generating microRNA (miRNA) duplexes and short interfering RNA duplexes with 20~23 nucleotides (nts) in length. The typical form of pre-miRNA processed by the Drosha protein is a hairpin RNA with 2-nt 3' overhangs. On the other hand, production of mature miRNA from an endogenous hairpin RNA with 5' overhangs has also been reported, although the mechanism for this process is unknown.ResultsIn this study, we show that human recombinant DICER protein (rDICER) processes a hairpin RNA with 5' overhangsin vitroand generates an intermediate duplex with a 29 nt-5' strand and a 23 nt-3' strand, which was eventually cleaved into a canonical miRNA duplex via a two-step cleavage. The previously identified endogenous pre-miRNA with 5' overhangs, pre-mmu-mir-1982 RNA, is also determined to be a substrate of rDICER through the same two-step cleavage.ConclusionsThe two-step cleavage of a hairpin RNA with 5' overhangs shows that DICER releases double-stranded RNAs after the first cleavage and binds them again in the inverse direction for a second cleavage. These findings have implications for how DICER may be able to interact with or process differing precursor structures.
Variable expressivity of FGF3 mutations associated with deafness and LAMM syndrome
Authors: Riazuddin Saima , Ahmed Zubair M , Hegde Rashmi S , Khan Shaheen N , Nasir Idrees , Shaukat Uzma , Riazuddin Sheikh , Butman John A , Griffith Andrew J , Friedman Thomas B , Choi Byung Yoon 
Published: February 2011

Abstract

Background
Recessive mutations of fibroblast growth factor 3 (FGF3) can cause LAMM syndrome (OMIM 610706), characterized by fully penetrant complete labyrinthine aplasia, microtia and microdontia.

Methods
We performed a prospective molecular genetic and clinical study of families segregating hearing loss linked to FGF3 mutations. Ten affected individuals from three large Pakistani families segregating FGF3 mutations were imaged with CT, MRI, or both to detect inner ear abnormalities. We also modeled the three dimensional structure of FGF3 to better understand the structural consequences of the three missense mutations.

Results
Two families segregated reported mutations (p.R104X and p.R95W) and one family segregated a novel mutation (p.R132GfsX26) of FGF3. All individuals homozygous for p.R104X or p.R132GfsX26 had fully penetrant features of LAMM syndrome. However, recessive p.R95W mutations were associated with nearly normal looking auricles and variable inner ear structural phenotypes, similar to that reported for a Somali family also segregating p.R95W. This suggests that the mild phenotype is not entirely due to genetic background. Molecular modeling result suggests a less drastic effect of p.R95W on FGF3 function compared with known missense mutations detected in fully penetrant LAMM syndrome. Since we detected significant intrafamilial variability of the inner ear structural phenotype in the family segregating p.R95W, we also sequenced FGF10 as a likely candidate for a modifier. However, we did not find any sequence variation, pointing out that a larger sample size will be needed to map and identify a modifier. We also observed a mild to moderate bilateral conductive hearing loss in three carriers of p.R95W, suggesting either a semi-dominant effect of this mutant allele of FGF3, otitis media, or a consequence of genetic background in these three family members.

Conclusions
We noted a less prominent dental and external ear phenotype in association with the homozygous p.R95W. Therefore, we conclude that the manifestations of recessive FGF3 mutations range from fully penetrant LAMM syndrome to deafness with residual inner ear structures and, by extension, with minimal syndromic features, an observation with implications for cochlear implantation candidacy.
The association of dimethylarginine dimethylaminohydrolase 1 gene polymorphism with type 2 diabetes: a cohort study
Authors: Lu Tse-Min , Lin Shing-Jong , Lin Ming-Wei , Hsu Chiao-Po , Chung Ming-Yi 
Published: February 2011

Abstract

Background
Elevated plasma levels of asymmetric dimethylarginine (ADMA) has been reported to be associated with insulin resistance and micro/macrovascular diabetic complications, and may predict cardiovascular events in type 2 diabetic patients. Dimethylarginine dimethylaminohydrolase 1 (DDAH1) is the major enzyme eliminating ADMA in humans, but the effect of genetic variations in DDAH1 on type 2 diabetes and its long-term outcome are unknown.

Methods
From July 2006 to June 2009, we assessed the association between polymorphisms in DDAH1 and type 2 diabetes in 814 consecutive unrelated subjects, including 309 type 2 diabetic patients and 505 non-diabetic individuals. Six single nucleotide polymorphisms (SNPs) in DDAH1, rs233112, rs1498373, rs1498374, rs587843, rs1403956, and rs1241321 were analyzed. Plasma ADMA levels were determined by high performance liquid chromatography. Insulin sensitivity was assessed by the homeostasis model assessment of insulin resistance (HOMA-IR).

Results
Among the 6 SNPs, only rs1241321 was significantly associated with a decreased risk of type 2 diabetes (AA vs GG+AG, OR = 0.64, 95% CI 0.47-0.86, p = 0.004). The association remained unchanged after adjustment for plasma ADMA level. The fasting plasma glucose and log HOMA-IR tended to be lower in subjects carrying the homozygous AA genotype of rs1241321 compared with the GG+AG genotypes. Over a median follow-up period of 28.2 months, there were 44 all-cause mortality and 50 major adverse cardiovascular events (MACE, including cardiovascular death, non-fatal myocardial infarction and stroke). Compared with the GG and AG genotypes, the AA genotype of rs1241321 was associated with reduced risk of MACE (HR = 0.31, 95% CI: 0.11-0.90, p = 0.03) and all-cause mortality (HR = 0.18, 95% CI: 0.04-0.80, p = 0.02) only in subgroup with type 2 diabetes. One common haplotype (GGCAGC) was found to be significantly associated with a decreased risk of type 2 diabetes (OR = 0.67, 95% CI = 0.46-0.98, p = 0.04).

Conclusions
Our results provide the first evidence that SNP rs1241321 in DDAH1 is associated with type 2 diabetes and its long-term outcome.
Fraternal twins: Swiprosin-1/EFhd2 and Swiprosin-2/EFhd1, two homologous EF-hand containing calcium binding adaptor proteins with distinct functions
Authors: Dütting Sebastian , Brachs Sebastian , Mielenz Dirk 
Published: February 2011

AbstractChanges in the intracellular calcium concentration govern cytoskeletal rearrangement, mitosis, apoptosis, transcriptional regulation or synaptic transmission, thereby, regulating cellular effector and organ functions. Calcium binding proteins respond to changes in the intracellular calcium concentration with structural changes, triggering enzymatic activation and association with downstream proteins. One type of calcium binding proteins are EF-hand super family proteins. Here, we describe two recently discovered homologous EF-hand containing adaptor proteins, Swiprosin-1/EF-hand domain containing 2 (EFhd2) and Swiprosin-2/EF-hand domain containing 1 (EFhd1), which are related to allograft inflammatory factor-1 (AIF-1). For reasons of simplicity and concision we propose to name Swiprosin-1/EFhd2 and Swiprosin-2/EFhd1 from now on EFhd2 and EFhd1, according to their respective gene symbols. AIF-1 and Swiprosin-1/EFhd2 are already present inBilateria, for instance inDrosophila melanogasterandCaenhorhabditis elegans. Swiprosin-2/EFhd1 arose later from gene duplication in the tetrapodal lineage. Secondary structure prediction of AIF-1 reveals disordered regions and one functional EF-hand. Swiprosin-1/EFhd2 and Swiprosin-2/EFhd1 exhibit a disordered region at the N-terminus, followed by two EF-hands and a coiled-coil domain. Whereas both proteins are similar in their predicted overall structure they differ in a non-homologous stretch of 60 amino acids just in front of the EF-hands. AIF-1 controls calcium-dependent cytoskeletal rearrangement in innate immune cells by means of its functional EF-hand. We propose that Swiprosin-1/EFhd2 as well is a cytoskeleton associated adaptor protein involved in immune and brain cell function. Pro-inflammatory conditions are likely to modulate expression and function of Swiprosin-1/EFhd2. Swiprosin-2/EFhd1, on the other hand, modulates apoptosis and differentiation of neuronal and muscle precursor cells, probably through an association with mitochondria. We suggest furthermore that Swiprosin-2/EFhd1 is part of a cellular response to oxidative stress, which could explain its pro-survival activity in neuronal, muscle and perhaps some malignant tissues.
Dosimetric accuracy of tomotherapy dose calculation in thorax lesions
Authors: Ardu Veronica , Broggi Sara , Cattaneo Giovanni Mauro , Mangili Paola , Calandrino Riccardo 
Published: February 2011

Abstract

Background
To analyse limits and capabilities in dose calculation of collapsed-cone-convolution (CCC) algorithm implemented in helical tomotherapy (HT) treatment planning system for thorax lesions.

Methods
The agreement between measured and calculated dose was verified both in homogeneous (Cheese Phantom) and in a custom-made inhomogeneous phantom. The inhomogeneous phantom was employed to mimic a patient's thorax region with lung density encountered in extreme cases and acrylic inserts of various dimensions and positions inside the lung cavity. For both phantoms, different lung treatment plans (single or multiple metastases and targets in the mediastinum) using HT technique were simulated and verified. Point and planar dose measurements, both with radiographic extended-dose-range (EDR2) and radiochromic external-beam-therapy (EBT2) films, were performed. Absolute point dose measurements, dose profile comparisons and quantitative analysis of gamma function distributions were analyzed.

Results
An excellent agreement between measured and calculated dose distributions was found in homogeneous media, both for point and planar dose measurements. Absolute dose deviations <3% were found for all considered measurement points, both inside the PTV and in critical structures. Very good results were also found for planar dose distribution comparisons, where at least 96% of all points satisfied the gamma acceptance criteria (3%-3 mm), both for EDR2 and for EBT2 films. Acceptable results were also reported for the inhomogeneous phantom. Similar point dose deviations were found with slightly worse agreement for the planar dose distribution comparison: 96% of all points passed the gamma analysis test with acceptable levels of 4%-4 mm and 5%-4 mm, for EDR2 and EBT2 films respectively. Lower accuracy was observed in high dose/low density regions, where CCC seems to overestimate the measured dose around 4-5%.

Conclusions
Very acceptable accuracy was found for complex lung treatment plans calculated with CCC algorithm implemented in the tomotherapy TPS even in the heterogeneous phantom with very low lung-density.