bluuebunny/crossref_metadata_2025_split huggingface dataset:
Genome-wide analysis of chicken snoRNAs provides unique implications for the evolution of vertebrate snoRNAs
Authors: Shao Peng , Yang Jian-Hua , Zhou Hui , Guan Dao-Gang , Qu Liang-Hu 
Published: February 2009

Abstract

Background
Small nucleolar RNAs (snoRNAs) represent one of the largest groups of functionally diverse trans-acting non-protein-coding (npc) RNAs currently known in eukaryotic cells. Chicken snoRNAs have been very poorly characterized when compared to other vertebrate snoRNAs. A genome-wide analysis of chicken snoRNAs is therefore of great importance to further understand the functional evolution of snoRNAs in vertebrates.

Results
Two hundred and one gene variants encoding 93 box C/D and 62 box H/ACA snoRNAs were identified in the chicken genome and are predicted to guide 86 2'-O-ribose methylations and 69 pseudouridylations of rRNAs and spliceosomal RNAs. Forty-four snoRNA clusters were grouped into four categories based on synteny characteristics of the clustered snoRNAs between chicken and human. Comparative analyses of chicken snoRNAs revealed extensive recombination and separation of guiding function, with cooperative evolution between the guiding duplexes and modification sites. The gas5-like snoRNA host gene appears to be a hotspot of snoRNA gene expansion in vertebrates. Our results suggest that the chicken is a good model for the prediction of functional snoRNAs, and that intragenic duplication and divergence might be the major driving forces responsible for expansion of novel snoRNA genes in the chicken genome.

Conclusion
We have provided a detailed catalog of chicken snoRNAs that aids in understanding snoRNA gene repertoire differences between avians and other vertebrates. Our genome-wide analysis of chicken snoRNAs improves annotation of the 'darkness matter' in the npcRNA world and provides a unique perspective into snoRNA evolution in vertebrates.
Genome-wide analysis of the PreA/PreB (QseB/QseC) regulon of Salmonella enterica serovar Typhimurium
Authors: Merighi Massimo , Septer Alecia N , Carroll-Portillo Amanda , Bhatiya Aditi , Porwollik Steffen , McClelland Michael , Gunn John S 
Published: February 2009

Abstract

Background
The Salmonella PreA/PreB two-component system (TCS) is an ortholog of the QseBC TCS of Escherichia coli. In both Salmonella and E. coli, this system has been shown to affect motility and virulence in response to quorum-sensing and hormonal signals, and to affect the transcription of the Salmonella enterica serovar Typhimurium (S. Typhimurium) pmrAB operon, which encodes an important virulence-associated TCS.

Results
To determine the PreA/PreB regulon in S. Typhimurium, we performed DNA microarrays comparing the wild type strain and various preA and/or preB mutants in the presence of ectopically expressed preA (qseB). These data confirmed our previous findings of the negative effect of PreB on PreA gene regulation and identified candidate PreA-regulated genes. A proportion of the activated loci were previously identified as PmrA-activated genes (yibD, pmrAB, cptA, etc.) or were genes located in the local region around preA, including the preAB operon. The transcriptional units were defined in this local region by RT-PCR, suggesting three PreA activated operons composed of preA-preB, mdaB-ygiN, and ygiW-STM3175. Several putative virulence-related phenotypes were examined for preAB mutants, resulting in the observation of a host cell invasion and slight virulence defect of a preAB mutant. Contrary to previous reports on this TCS, we were unable to show a PreA/PreB-dependent effect of the quorum-sensing signal AI-2 or of epinephrine on S. Typhimurium with regard to bacterial motility.

Conclusion
This work further characterizes this unorthadox OmpR/EnvZ class TCS and provides novel candidate regulated genes for further study. This first in-depth study of the PreA/PreB regulatory system phenotypes and regulation suggests significant comparative differences to the reported function of the orthologous QseB/QseC in E. coli.
Transcriptional inhibiton of Hoxd4 expression by miRNA-10a in human breast cancer cells
Authors: Tan Yuliang , Zhang Bo , Wu Tao , Skogerbø Geir , Zhu Xiaopeng , Guo Xiangqian , He Shunmin , Chen Runsheng 
Published: February 2009

Abstract

Background
Small noncoding RNAs (ncRNAs), including short interfering RNAs (siRNAs) and microRNAs (miRNAs), can silence genes at the transcriptional, post-transcriptional or translational level [1, 2].

Results
Here, we show that microRNA-10a (miR-10a) targets a homologous DNA region in the promoter region of the hoxd4 gene and represses its expression at the transcriptional level. Mutational analysis of the miR-10a sequence revealed that the 3' end of the miRNA sequence is the most critical element for the silencing effect. MicroRNA-10a-induced transcriptional gene inhibition requires the presence of Dicer and Argonautes 1 and 3, and it is related to promoter associated noncoding RNAs. Bisulfite sequencing analysis showed that the reduced hoxd4 expression was accompanied by de novo DNA methylation at the hoxd4 promoter. We further demonstrated that trimethylation of histone 3 lysine 27 (H3K27me3) is involved in the miR-10a-induced hoxd4 transcriptional gene silence.

Conclusion
In conclusion, our results demonstrate that miR-10a can regulate human gene expression in a transcriptional manner, and indicate that endogenous small noncoding RNA-induced control of transcription may be a potential system for expressional regulation in human breast cancer cells.
Genetic correction of splice site mutation in purified and enriched myoblasts isolated from mdx5cv mice
Authors: Maguire Katie , Suzuki Takayuki , DiMatteo Darlise , Parekh-Olmedo Hetal , Kmiec Eric 
Published: February 2009

Abstract

Background
Duchenne Muscular Dystrophy (DMD) is an X-linked genetic disorder that results in the production of a dysfunctional form of the protein, dystrophin. The mdx5cv mouse is a model of DMD in which a point mutation in exon 10 of the dystrophin gene creates an artificial splice site. As a result, a 53 base pair deletion of exon 10 occurs with a coincident creation of a frameshift and a premature stop codon. Using primary myoblasts from mdx5cv mice, single-stranded DNA oligonucleotides were designed to correct this DNA mutation.

Results
Single-stranded DNA oligonucleotides that were designed to repair this splice site mutation corrected the mutation in the gene and restored expression of wild-type dystrophin. This repair was validated at the DNA, RNA and protein level. We also report that the frequency of genetic repair of the mdx mutation can be enhanced if RNAi is used to suppress expression of the recombinase inhibitor protein Msh2 in cultures containing myoblasts but not in those heavily enriched in myoblasts.

Conclusion
Exogenous manipulations, such as RNAi, are certainly feasible and possibly required to increase the successful application of gene repair in some primary or progenitor muscle cells.
CD133+adult human retinal cells remain undifferentiated in Leukaemia Inhibitory Factor (LIF)
Authors: Carter Debra A , Dick Andrew D , Mayer Eric J 
Published: February 2009

Abstract

Background
CD133 is a cell surface marker of haematopoietic stem and progenitor cells. Leukaemia inhibitory factor (LIF), sustains proliferation and not differentiation of embryonic stem cells. We used CD133 to purify adult human retinal cells and aimed to determine what effect LIF had on these cultures and whether they still had the ability to generate neurospheres.

Methods
Retinal cell suspensions were derived from adult human post-mortem tissue with ethical approval. With magnetic automated cell sorting (MACS) CD133+ retinal cells were enriched from post mortem adult human retina. CD133+ retinal cell phenotype was analysed by flow cytometry and cultured cells were observed for proliferative capacity, neuropshere generation and differentiation with or without LIF supplementation.

Results
We demonstrated purification (to 95%) of CD133+ cells from adult human postmortem retina. Proliferating cells were identified through BrdU incorporation and expression of the proliferation markers Ki67 and Cyclin D1. CD133+ retinal cells differentiated whilst forming neurospheres containing appropriate lineage markers including glia, neurons and photoreceptors. LIF maintained CD133+ retinal cells in a proliferative and relatively undifferentiated state (Ki67, Cyclin D1 expression) without significant neurosphere generation. Differentiation whilst forming neurospheres was re-established on LIF withdrawal.

Conclusion
These data support the evidence that CD133 expression characterises a population of cells within the resident adult human retina which have progenitor cell properties and that their turnover and differentiation is influenced by LIF. This may explain differences in retinal responses observed following disease or injury.
Factors determining the outcome of children hospitalized with severe pneumonia
Authors: Tiewsoh Karalanglin , Lodha Rakesh , Pandey Ravindra M , Broor Shobha , Kalaivani M , Kabra Sushil K 
Published: February 2009

AbstractBackgroundPneumonia is one of the leading causes of morbidity and mortality in under fives. We carried out a comprehensive study to identify factors influencing both mortality and morbidity for children less than 5 years of age hospitalized with severe pneumonia.Methods200 hospitalized children aged 2–60 months with World Health Organization (WHO) defined severe pneumonia were enrolled in the study. The children were managed using a standard protocol. They were closely followed up for need for change in antibiotics, prolonged hospital stay, need for mechanical ventilation and mortality. Data on the factors influencing the outcome were collected.ResultsOf 200 children enrolled in the study, 113 (56.5%) needed a change in antibiotics, 102 (51%) stayed for more than 5 days in the hospital, 41 (20.5%) needed mechanical ventilation and 21 (10.5%) died. On multivariate analysis, lack of exclusive breastfeeding [RR (95%CI) 2.63 (2.16–2.86)], overcrowding [RR (95%CI) 1.94 (1.35–2.38)] and an abnormal chest x-ray [RR (95%CI) 2.29 (1.22–3.44)] were associated with the need for change of antibiotics. Lack of exclusive breastfeeding [RR (95%CI) 2.56 (2.0–2.93)], overcrowding [RR (95%CI) 2.59 (1.78–3.23)] and an abnormal chest x-ray [RR (95%CI) 2.99 (1.65–4.38)] were identified as determinants for prolonged hospital stay. Head nodding [RR (95%CI) 8.34 (2.71–12.77)], altered sensorium [RR (95%CI) 5.44 (1.34–17.56)], abnormal leukocyte counts [RR (95%CI) 5.85(1.36–17.14)] and pallor [RR (95%C) 10.88 (2.95–20.40)] were associated with mortality. Head nodding (RR (95% CI) 4.73 (1.50–6.36)] and cyanosis (RR (95%CI) 5.06 (1.80–11.34)] were the determining factors for mechanical ventilation.In radiographically confirmed pneumonia, the determining factors for change of antibiotics were: lack of exclusive breast feeding [RR (95% CI) 2.05 (1.69–2.2)] and low birth weight [RR (95% CI) 1.59 (1.1–1.89)]. For prolonged hospital stay, the factors identified were mothers' education less than graduation [RR (95% CI) 1.5 (1.19–1.7)], lack of exclusive breast feeding [RR (95% CI) 1.77 (1.19–2.09)] and oxygen saturation of < 90% at time of presentation [RR (95% CI) 2.06 (1.42–2.42)]. Determinants for mechanical ventilation were mothers' education less than graduation [RR (95% CI) 3.6 (1.15–6.3)] and cyanosis at presentation [RR (95% CI) 10.9 (1.56–18.9)]. For mortality, the only determinant was pallor [RR (95% CI) 10.54 (1.8–21.79)].ConclusionChildren hospitalized with severe community acquired pneumonia [as defined by World Health Organization (WHO)] who had not received exclusive breast feeding, had stayed in an overcrowded homes and had an abnormal chest radiograph were more likely to fail to respond with primary antibiotic regimen and require change of antibiotics and prolonged hospital stay.In children with radiographically confirmed pneumonia, lack of breast feeding and low birth weight was associated with need for change in antibiotics.
Potential and Actual Terrestrial Rabies Exposures in People and Domestic Animals, Upstate South Carolina, 1994–2004: A Surveillance Study
Authors: Roseveare Catherine W , Goolsby W David , Foppa Ivo M 
Published: February 2009

AbstractBackgroundAlthough there has been a reduction of rabies in pets and domestic animals during recent decades in the United States, rabies remains enzootic among bats and several species of terrestrial wildlife. Spillover transmission of wildlife rabies to domestic animals therefore remains a public health threatMethodsRetrospective analysis of surveillance data of reported animal incidents (bites, scratches, mucous membrane contacts) from South Carolina, 1995 to 2003, was performed to assess risk factors of potential rabies exposures among human and animal victims.ResultsDogs and cats contributed the majority (66.7% and 26.4%, respectively) of all reported incidents, with stray dogs and cats contributing 9.0% and 15.1 respectively. Current rabies vaccination status of dogs and cats (40.2% and 13.8%, respectively) were below World Health Organization recommended levels. Owned cats were half as likely to be vaccinated for rabies as dogs (OR 0.53, 95% CI 0.48, 0.58). Animal victims were primarily exposed to wildlife (83.0%), of which 27.5% were rabid. Almost 90% of confirmed rabies exposures were due to wildlife. Skunks had the highest prevalence of rabies among species of exposure animals (63.2%). Among rabid domestic animals, stray cats were the most commonly reported (47.4%).ConclusionWhile the majority of reported potential rabies exposures are associated with dog and cat incidents, most rabies exposures derive from rabid wildlife. Stray cats were most frequently rabid among domestic animals. Our results underscore the need for improvement of wildlife rabies control and the reduction of interactions of domestic animals, including cats, with wildlife.
Incorporating double copies of a chromatin insulator into lentiviral vectors results in less viral integrants
Authors: Nielsen Troels T , Jakobsson Johan , Rosenqvist Nina , Lundberg Cecilia 
Published: February 2009

Abstract

Background
Lentiviral vectors hold great promise as gene transfer vectors in gene therapeutic settings. However, problems related to the risk of insertional mutagenesis, transgene silencing and positional effects have stalled the use of such vectors in the clinic. Chromatin insulators are boundary elements that can prevent enhancer-promoter interactions, if placed between these elements, and protect transgene cassettes from silencing and positional effects. It has been suggested that insulators can improve the safety and performance of lentiviral vectors. Therefore insulators have been incorporated into lentiviral vectors in order to enhance their safety profile and improve transgene expression. Commonly such insulator vectors are produced at lower titers than control vectors thus limiting their potential use.

Results
In this study we cloned in tandem copies of the chicken β-globin insulator (cHS4) on both sides of the transgene cassette in order to enhance the insulating effect. Our insulator vectors were produced at significantly lower titers compared to control vectors, and we show that this reduction in titer is due to a block during the transduction process that appears after reverse transcription but before integration of the viral DNA. This non-integrated viral DNA could be detected by PCR and, importantly, prevented efficient transduction of target cells.

Conclusion
These results have importance for the future use of insulator sequences in lentiviral vectors and might limit the use of insulators in vectors for in vivo use. Therefore, a careful analysis of the optimal design must be performed before insulators are included into clinical lentiviral vectors.
The structure of the leukemia drug imatinib bound to human quinone reductase 2 (NQO2)
Authors: Winger Jonathan A , Hantschel Oliver , Superti-Furga Giulio , Kuriyan John 
Published: February 2009

AbstractBackgroundImatinib represents the first in a class of drugs targeted against chronic myelogenous leukemia to enter the clinic, showing excellent efficacy and specificity for Abl, Kit, and PDGFR kinases. Recent screens carried out to find off-target proteins that bind to imatinib identified the oxidoreductase NQO2, a flavoprotein that is phosphorylated in a chronic myelogenous leukemia cell line.ResultsWe examined the inhibition of NQO2 activity by the Abl kinase inhibitors imatinib, nilotinib, and dasatinib, and obtained IC50values of 80 nM, 380 nM, and >100 μM, respectively. Using electronic absorption spectroscopy, we show that imatinib binding results in a perturbation of the protein environment around the flavin prosthetic group in NQO2. We have determined the crystal structure of the complex of imatinib with human NQO2 at 1.75 Å resolution, which reveals that imatinib binds in the enzyme active site, adjacent to the flavin isoalloxazine ring. We find that phosphorylation of NQO2 has little effect on enzyme activity and is therefore likely to regulate other aspects of NQO2 function.ConclusionThe structure of the imatinib-NQO2 complex demonstrates that imatinib inhibits NQO2 activity by competing with substrate for the active site. The overall conformation of imatinib when bound to NQO2 resembles the folded conformation observed in some kinase complexes. Interactions made by imatinib with residues at the rim of the active site provide an explanation for the binding selectivity of NQO2 for imatinib, nilotinib, and dasatinib. These interactions also provide a rationale for the lack of inhibition of the related oxidoreductase NQO1 by these compounds. Taken together, these studies provide insight into the mechanism of NQO2 inhibition by imatinib, with potential implications for drug design and treatment of chronic myelogenous leukemia in patients.
Cognition, learning behaviour and hippocampal synaptic plasticity are not disrupted in mice over-expressing the cholesterol transporter ABCG1
Authors: Parkinson Pamela F , Kannangara Timal S , Eadie Brennan D , Burgess Braydon L , Wellington Cheryl L , Christie Brian R 
Published: February 2009

Abstract

Background
Cognitive deficits are a hallmark feature of both Down Syndrome (DS) and Alzheimer's Disease (AD). Extra copies of the genes on chromosome 21 may also play an important role in the accelerated onset of AD in DS individuals. Growing evidence suggests an important function for cholesterol in the pathogenesis of AD, particularly in APP metabolism and production of Aβ peptides. The ATP-Binding Cassette-G1 (ABCG1) transporter is located on chromosome 21, and participates in the maintenance of tissue cholesterol homeostasis.

Results
To assess the role of ABCG1 in DS-related cognition, we evaluated the cognitive performance of mice selectively over-expressing the ABCG1 gene from its endogenous regulatory signals. Both wild-type and ABCG1 transgenic mice performed equivalently on several behavioral tests, including measures of anxiety, as well as on reference and working memory tasks. No deficits in hippocampal CA1 synaptic plasticity as determined with electrophysiological studies were apparent in mice over-expressing ABCG1.

Conclusion
These findings indicate that although ABCG1 may play a role in maintaining cellular or tissue cholesterol homeostasis, it is unlikely that excess ABCG1 expression contributes to the cognitive deficits in DS individuals.
GO Explorer: A gene-ontology tool to aid in the interpretation of shotgun proteomics data
Authors: Carvalho Paulo C , Fischer Juliana SG , Chen Emily I , Domont Gilberto B , Carvalho Maria GC , Degrave Wim M , Yates John R , Barbosa Valmir C 
Published: February 2009

AbstractBackgroundSpectral counting is a shotgun proteomics approach comprising the identification and relative quantitation of thousands of proteins in complex mixtures. However, this strategy generates bewildering amounts of data whose biological interpretation is a challenge.ResultsHere we present a new algorithm, termed GO Explorer (GOEx), that leverages the gene ontology (GO) to aid in the interpretation of proteomic data. GOEx stands out because it combines data from protein fold changes with GO over-representation statistics to help draw conclusions. Moreover, it is tightly integrated within the PatternLab for Proteomics project and, thus, lies within a complete computational environment that provides parsers and pattern recognition tools designed for spectral counting. GOEx offers three independent methods to query data: an interactive directed acyclic graph, a specialist mode where key words can be searched, and an automatic search. Its usefulness is demonstrated by applying it to help interpret the effects of perillyl alcohol, a natural chemotherapeutic agent, on glioblastoma multiform cell lines (A172). We used a new multi-surfactant shotgun proteomic strategy and identified more than 2600 proteins; GOEx pinpointed key sets of differentially expressed proteins related to cell cycle, alcohol catabolism, the Ras pathway, apoptosis, and stress response, to name a few.ConclusionGOEx facilitates organism-specific studies by leveraging GO and providing a rich graphical user interface. It is a simple to use tool, specialized for biologists who wish to analyze spectral counting data from shotgun proteomics. GOEx is available athttp://pcarvalho.com/patternlab.
Turkish version of impact on family scale: a study of reliability and validity
Authors: Bek Nilgun , Simsek I Engin , Erel Suat , Yakut Yavuz , Uygur Fatma 
Published: February 2009

AbstractBackgroundAlthough there is a considerably high prevalence of developmental disorders in Turkey there are not many assessment tools related to evaluating the impact of these children on their family. The aim of this study was to determine the validity and reliability of the Turkish version of the Impact on Family Scale (IPFAM), a health related quality of life measurement to be utilized in clinical trials, health care services, research and evaluation.MethodsCaregivers of 85 children with developmental disabilities answered the questionnaire and 65 of them answered it twice with a one week interval. The reliability of the measurement was assessed by Cronbach's alpha coefficient, and with intraclass correlation coefficient (ICC) for test-retest reliability. Construct validity was assessed by calculating the correlation between total impact score of IPFAM, WeeFIM and the physiotherapists' evaluation via Visual Analogue Scale (VAS) to determine the child's disability.ResultsTest-retest reliability was found to be ICC = 0.953 for total impact, 0.843 for financial support, 0.940 for general impact, 0.871 for disruption of social relations and 0.787 for coping. Internal consistency was tested using Cronbach's alpha and was found to be 0.902 for total impact of IPFAM. For construct validity the correlation between total impact score of IPFAM and WeeFIM was r = -0,532 (p < 0.001) and the correlation between total impact score of IPFAM and the physiotherapist's evaluation was r = 0.519 (p < 0.001).ConclusionThe Turkish version of IPFAM was found to be a reliable and valid instrument for assessing the impact of developmental disorders of the child on the family.