bluuebunny/crossref_metadata_2025_split huggingface dataset:
RNA-dependent inhibition of ribonucleotide reductase is a major pathway for 5-azacytidine activity in acute myeloid leukemia
Authors: Aimiuwu Josephine , Wang Hongyan , Chen Ping , Xie Zhiliang , Wang Jiang , Liu Shujun , Klisovic Rebecca , Mims Alice , Blum William , Marcucci Guido , Chan Kenneth K. 
Published: April 2012

Abstract
5-Azacytidine (5-azaC) is an azanucleoside approved for myelodysplastic syndrome. Approximately 80%-90% of 5-azaC is believed to be incorporated into RNA, which disrupts nucleic acid and protein metabolism leading to apoptosis. A smaller fraction (10%-20%) of 5-azaC inhibits DNA methylation and synthesis through conversion to decitabine triphosphate and subsequent DNA incorporation. However, its precise mechanism of action remains unclear. Ribonucleotide reductase (RR) is a highly regulated enzyme comprising 2 subunits, RRM1 and RRM2, that provides the deoxyribonucleotides required for DNA synthesis/repair. In the present study, we found for the first time that 5-azaC is a potent inhibitor of RRM2 in leukemia cell lines, in a mouse model, and in BM mononuclear cells from acute myeloid leukemia (AML) patients. 5-azaC–induced RRM2 gene expression inhibition involves its direct RNA incorporation and an attenuated RRM2 mRNA stability. Therefore, 5-azaC causes a major perturbation of deoxyribonucleotide pools. We also demonstrate herein that the initial RR-mediated 5-azaC conversion to decitabine is terminated through its own inhibition. In conclusion, we identify RRM2 as a novel molecular target of 5-azaC in AML. Our findings provide a basis for its more widespread clinical use either alone or in combination.
The interferon-dependent orchestration of innate and adaptive immunity after transplantation
Authors: Robb Renee J. , Hill Geoffrey R. 
Published: April 2012

AbstractThe therapeutic GVL effect after allogeneic stem cell transplantation is limited by the development of GVHD. The ultimate aim of current research is to separate the 2 processes in a meaningful fashion. The IFNs are a pleiotropic group of cytokines that were originally recognized because of their ability to interfere with viral replication. However, it is now established that these cytokines play an important role in orchestrating both innate and adaptive immunity. Multiple studies have investigated the effects of both types I and II IFN on GVHD and GVL in preclinical transplant models. The results indicate variable effects that are dependent on the period of activity within the developing immune response, the presence and type of pretransplant conditioning and the differential mechanisms, and IFN sensitivity of immune pathology within individual target organs during GVHD. This Perspective discusses the current literature on the IFNs and their potential modulation within clinical transplantation, focusing particularly on enhancing the therapeutic GVL effects.
Characterization of C-strain “Riems” TAV-epitope escape variants obtained through selective antibody pressure in cell culture
Authors: Leifer Immanuel , Blome Sandra , Blohm Ulrike , König Patricia , Küster Heike , Lange Bodo , Beer Martin 
Published: April 2012

Abstract
Classical swine fever virus (CSFV) C-strain “Riems” escape variants generated under selective antibody pressure with monoclonal antibodies and a peptide-specific antiserum in cell culture were investigated. Candidates with up to three amino acid exchanges in the immunodominant and highly conserved linear TAV-epitope of the E2-glycoprotein, and additional mutations in the envelope proteins ERNS and E1, were characterized both in vitro and in vivo.
It was further demonstrated, that intramuscular immunization of weaner pigs with variants selected after a series of passages elicited full protection against lethal CSFV challenge infection. These novel CSFV C-strain variants with exchanges in the TAV-epitope present potential marker vaccine candidates. The DIVA (differentiating infected from vaccinated animals) principle was tested for those variants using commercially available E2 antibody detection ELISA. Moreover, direct virus differentiation is possible using a real-time RT-PCR system specific for the new C-strain virus escape variants or using differential immunofluorescence staining.
Characterization of a novel chaperone/usher fimbrial operon present on KpGI-5, a methionine tRNA gene-associated genomic island in Klebsiella pneumoniae
Authors: van Aartsen Jon J , Stahlhut Steen G , Harrison Ewan M , Crosatti Marialuisa , Ou Hong-Yu , Krogfelt Karen A , Struve Carsten , Rajakumar Kumar 
Published: April 2012

Abstract

Background
Several strain-specific Klebsiella pneumoniae virulence determinants have been described, though these have almost exclusively been linked with hypervirulent liver abscess-associated strains. Through PCR interrogation of integration hotspots, chromosome walking, island-tagging and fosmid-based marker rescue we captured and sequenced KpGI-5, a novel genomic island integrated into the met56 tRNA gene of K. pneumoniae KR116, a bloodstream isolate from a patient with pneumonia and neutropenic sepsis.

Results
The 14.0 kb KpGI-5 island exhibited a genome-anomalous G + C content, possessed near-perfect 46 bp direct repeats, encoded a γ1-chaperone/usher fimbrial cluster (fim2) and harboured seven other predicted genes of unknown function. Transcriptional analysis demonstrated expression of three fim2 genes, and suggested that the fim2A-fim2K cluster comprised an operon. As fimbrial systems are frequently implicated in pathogenesis, we examined the role of fim2 by analysing KR2107, a streptomycin-resistant derivative of KR116, and three isogenic mutants (Δfim, Δfim2 and ΔfimΔfim2) using biofilm assays, human cell adhesion assays and pair-wise competition-based murine models of intestinal colonization, lung infection and ascending urinary tract infection. Although no statistically significant role for fim2 was demonstrable, liver and kidney CFU counts for lung and urinary tract infection models, respectively, hinted at an ordered gradation of virulence: KR2107 (most virulent), KR2107∆fim2, KR2107∆fim and KR2107∆fim∆fim2 (least virulent). Thus, despite lack of statistical evidence there was a suggestion that fim and fim2 contribute additively to virulence in these murine infection models. However, further studies would be necessary to substantiate this hypothesis.

Conclusion
Although fim2 was present in 13% of Klebsiella spp. strains investigated, no obvious in vitro or in vivo role for the locus was identified, although there were subtle hints of involvement in urovirulence and bacterial dissemination from the respiratory tract. Based on our findings and on parallels with other fimbrial systems, we propose that fim2 has the potential to contribute beneficially to pathogenesis and/or environmental persistence of Klebsiella strains, at least under specific yet-to-be identified conditions.
The family of Deg/HtrA proteases in plants
Authors: Schuhmann Holger , Huesgen Pitter F , Adamska Iwona 
Published: April 2012

Abstract

Background
The Deg/HtrA family of ATP-independent serine endopeptidases is present in nearly all organisms from bacteria to human and vascular plants. In recent years, multiple deg/htrA protease genes were identified in various plant genomes. During genome annotations most proteases were named according to the order of discovery, hence the same names were sometimes given to different types of Deg/HtrA enzymes in different plant species. This can easily lead to false inference of individual protease functions based solely on a shared name. Therefore, the existing names and classification of these proteolytic enzymes does not meet our current needs and a phylogeny-based standardized nomenclature is required.

Results
Using phylogenetic and domain arrangement analysis, we improved the nomenclature of the Deg/HtrA protease family, standardized protease names based on their well-established nomenclature in Arabidopsis thaliana, and clarified the evolutionary relationship between orthologous enzymes from various photosynthetic organisms across several divergent systematic groups, including dicots, a monocot, a moss and a green alga. Furthermore, we identified a “core set” of eight proteases shared by all organisms examined here that might provide all the proteolytic potential of Deg/HtrA proteases necessary for a hypothetical plant cell.

Conclusions
In our proposed nomenclature, the evolutionarily closest orthologs have the same protease name, simplifying scientific communication when comparing different plant species and allowing for more reliable inference of protease functions. Further, we proposed that the high number of Deg/HtrA proteases in plants is mainly due to gene duplications unique to the respective organism.
Evaluation of the clinical value of ELISA based on MPT64 antibody aptamer for serological diagnosis of pulmonary tuberculosis
Authors: Zhu Changtai , Liu Jinming , Ling Yang , Yang Hua , Liu Zhonghua , Zheng Ruijuan , Qin Lianhua , Hu Zhongyi 
Published: April 2012

Abstract

Background
Presently, tuberculosis (TB) poses a global threat to human health. The development of reliable laboratory tools is vital to the diagnosis and treatment of TB. MPT64, a protein secreted by Mycobacterium tuberculosis complex, is highly specific for TB, making antibody to MPT64 a reagent specific for the diagnosis of TB.

Method
Antibody to MPT64 was obtained by a combination of genetic engineering and immunization by the system evolution of ligands by exponential enrichment. A high-affinity aptamer of antibody to MPT64 was selected from a random single-stranded DNA library, and a sandwich ELISA method based on this aptamer was developed. This ELISA method was used to detect TB in 328 serum samples, 160 from patients with pulmonary TB (PTB) and 168 from non-tuberculous controls.

Results
The minimum limit of detection of the ELISA method was 2.5 mg/L, and its linear range varied from 10 mg/L to 800 mg/L. Its sensitivity, specificity, positive likelihood ratio, negative likelihood ratio and area under the curve, with 95 % confidence intervals, were 64.4 % (56.7 %–71.4 %), 99.4 % (96.7 %–99.9 %), 108.2 (15.3–765.9), 0.350 (0.291–0.442) and 0.819 (0.770–0.868), respectively. No significant difference in sensitivity was observed between sputum smear positive (73/112, 65.2 %) and negative (30/48, 62.5 %) individuals.

Conclusions
This sandwich ELISA based on an MPT64 antibody aptamer may be useful for the serological diagnosis of PTB, both in sputum smear positive and negative patients.
Beta catenin and cytokine pathway dysregulation in patients with manifestations of the "PTEN hamartoma tumor syndrome"
Authors: Galatola Martina , Paparo Lorella , Duraturo Francesca , Turano Mimmo , Rossi Giovanni Battista , Izzo Paola , De Rosa Marina 
Published: April 2012

Abstract

Background
The "PTEN hamartoma tumor syndrome" (PHTS) includes a group of syndromes caused by germline mutations within the tumor suppressor gene "phosphatase and tensin homolog deleted on chromosome ten" (PTEN), characterized by multiple polyps in the gastrointestinal tract and by a highly increased risk of developing malignant tumours in many tissues.
The current work clarifies the molecular basis of PHTS in three unrelated Italian patients, and sheds light on molecular pathway disregulation constitutively associated to PTEN alteration.

Methods
We performed a combination of RT-PCR, PCR, sequencing of the amplified fragments, Real Time PCR and western blot techniques.

Results
Our data provide the first evidence of β-catenin accumulation in blood cells of patients with hereditary cancer syndrome caused by germ-line PTEN alteration. In addition, for the first time we show, in all PHTS patients analysed, alterations in the expression of TNFα, its receptors and IL-10. Importantly, the isoform of TNFRI that lacks the DEATH domain (TNFRSF1β) was found to be overexpressed.

Conclusion
In light of our findings, we suggest that the PTEN pathway disregulation could determine, in non-neoplastic cells of PHTS patients, cell survival and pro-inflammatory stimulation, mediated by the expression of molecules such as β-catenin, TNFα and TNFα receptors, which could predispose these patients to the development of multiple cancers.
Genotyping of a tri-allelic polymorphism by a novel melting curve assay in MTHFD1L: an association study of nonsyndromic Cleft in Ireland
Authors: Minguzzi Stefano , Molloy Anne M , Peadar Kirke , Mills James , Scott John M , Troendle James , Pangilinan Faith , Brody Lawrence , Parle-McDermott Anne 
Published: April 2012

Abstract

Background
Polymorphisms within the MTHFD1L gene were previously associated with risk of neural tube defects in Ireland. We sought to test the most significant MTHFD1L polymorphisms for an association with risk of cleft in an Irish cohort. This required the development of a new melting curve assay to genotype the technically challenging MTHFD1L triallelic deletion/insertion polymorphism (rs3832406).

Methods
Melting curve analysis was used to genotype the MTHFD1L triallelic deletion/insertion polymorphism (rs3832406) and a Single Nucleotide Polymorphism rs17080476 in an Irish cohort consisting of 981 Irish case-parent trios and 1,008 controls. Tests for association with nonsyndromic cleft lip with or without cleft palate and cleft palate included case/control analysis, mother/control analysis and Transmission Disequilibrium Tests of case-parent trios.

Results
A successful melting curve genotyping assay was developed for the deletion/insertion polymorphism (rs3832406). The TDT analysis initially showed that the rs3832406 polymorphism was associated with isolated cleft lip with or without cleft palate. However, corrected p-values indicated that this association was not significant.

Conclusions
Melting Curve Analysis can be employed to successfully genotype challenging polymorphisms such as the MTHFD1L triallelic deletion/insertion polymorphism (DIP) reported here (rs3832406) and is a viable alternative to capillary electrophoresis. Corrected p-values indicate no association between MTHFD1L and risk of cleft in an Irish cohort.
Association analysis between HOXD9 genes and the development of developmental dysplasia of the hip in Chinese female Han population
Authors: Tian Wei , Zhao Lixi , Wang Jing , Suo Peisu , Wang Jianmin , Cheng Longfei , Cheng Zhi , Jia Jian , Kan Shilian , Wang Binbin , Ma Xu 
Published: April 2012

AbstractBackgroundDevelopmental dysplasia of the hip (DDH) is a congenital or acquired deformation or misalignment of the hip joint which affects mainly females. We hypothesized thatHOXD9gene could be regulated in acetabular size or shape and related in DDH developing.MethodsTwo hundred and nine Chinese Han female DDH patients and 173 ethnic, age matched healthy female controls were genotyped forHOXD9two tag SNPs using sequenom method.ResultsOne of the two tag SNPs, rs711822, was not shown significantly differences in genotypic or allelic distribution between case and control group. Comparing the genotypic distribution of rs711819, there was significant differences between DDH patients group and control group (χ2 = 7.54, df =2,P=0.023), and the association to DDH developing reached significance (P=0.045, OR =1.79, 95 % CI: 1.01-3.17 by dominant mode).ConclusionIn conclusion, the association between one tag SNP ofHOXD9gene and the development of DDH reach significant in our study population, this result indicate the positive correlation betweenHOXD9gene and DDH developing. Further study in larger sample size and different population as well as functional studies will help to understand the pathogenesis of DDH.
Assessment of leukemia inhibitory factor and glycoprotein 130 expression in endometrium and uterine flushing: a possible diagnostic tool for impaired fertility
Authors: Tawfeek Manal A , Eid Manal A , Hasan Azza M , Mostafa Manal , El-Serogy Hesham A 
Published: April 2012

Abstract

Background
Uterine receptivity and implantation are complex processes requiring coordinated expression of molecules by zygote and uterus. Our objective was to evaluate the role of the endometrial expression of leukemia inhibitory factor (LIF) and its glycoprotein 130 (gp130) receptor molecules and their secretion in uterine flushing during the window of implantation in cases of primary unexplained infertility

Case presentation
The study was conducted on 25 infertile women with unexplained infertility for at least two years and 10 normal fertile women as a control group . Endometrial tissue and uterine flushing were obtained. Each tissue specimen was divided into two pieces; one piece was used for histological dating of the endometrium and for immunostaining of progesterone receptors, and the second was used for RNA extraction and PCR assay of LIF and gp130 mRNA expression. Serum estrogen and progesterone were measured for all subjects. LIF mRNA was expressed in the endometrium of all normal fertile women but significantly decreased in infertile women. LIF was not detectable in 88% of infertile women while it was fairly detectable in 12% of them. Gp130 mRNA was hardly detectable in both fertile and infertile women with no difference between them. Infertile women secreted significantly less LIF and gp130 molecules in the uterine flushing compared with normal fertile women.

Conclusions
Expression of LIF mRNA in endometrium could be used as a molecular marker of unexplained infertility. Assessment of secreted LIF and gp130 molecules in uterine flushing could be another useful and safe method for predicting successful implantation as well as for diagnosing and eventually treating women with impaired fertility using recombinant human LIF.
The use of complementary and alternative medicine (CAM) in children: a telephone-based survey in Korea
Authors: Kim Jung-Ha , Nam Chung-Mo , Kim Moo-Young , Lee Duk-Chul 
Published: April 2012

AbstractBackgroundThe purpose of this study was to estimate the prevalence and patterns of CAM use in Korean children via a telephone based survey. We also investigated parent satisfaction, a proxy for their child, with CAM therapy and determined the factors affecting satisfaction with CAM use.MethodsThis study used a landline telephone-based survey to examine a random sample representative of Korean children, aged 0 to 18 years. We assigned and surveyed 2,000 subjects according to age group, gender, and geographical distributions by proportionate quota and systematic sampling of children throughout Korea in 2010. A household of 1,184 with a 18.6% response rate was projected to yield 2,077 completed data. We performed statistical analyses using sampling weight.ResultsThe prevalence of CAM use was 65.3% for the Korean children in our sample population. The most commonly used CAM category was natural products (89.3%). More than half of CAM user’s parents reported satisfaction with their therapies (52.7%), but only 29.1% among them had consulted a Western trained doctor regarding the CAM therapies used. Doctor visits were associated with lower satisfaction with CAM use but not with consultation rate with a doctor.ConclusionsOur study suggests that CAM is widely used among children in Korea. Medical doctors should actively discuss the use of CAM therapies with their patients and provide information on the safety and efficacy of diverse CAM modalities to guide the choices of CAM users.
Gene expression profiling of flaxseed in mouse lung tissues-modulation of toxicologically relevant genes
Authors: Dukes Floyd , Kanterakis Stathis , Lee James , Pietrofesa Ralph , Andersen Emily S , Arguiri Evguenia , Tyagi Sonia , Showe Louise , Amrani Yassine , Christofidou-Solomidou Melpo 
Published: April 2012

AbstractBackgroundFlaxseed (FS), a nutritional supplement consisting mainly of omega-3 fatty acids and lignan phenolics has potent anti-inflammatory, anti-fibrotic and antioxidant properties. The usefulness of flaxseed as an alternative and complimentary treatment option has been known since ancient times. We have shown that dietary FS supplementation ameliorates oxidative stress and inflammation in experimental models of acute and chronic lung injury in mice resulting from diverse toxicants. The development of lung tissue damage in response to direct or indirect oxidant stress is a complex process, associated with changes in expression levels of a number of genes. We therefore postulated that flaxseed might modulate gene expression of vital signaling pathways, thus interfering with the development of tissue injury.MethodsWe evaluated gene expression in lungs of flaxseed-fed (10%FS) mice under unchallenged, control conditions. We reasoned that array technology would provide a powerful tool for studying the mechanisms behind this response and aid the evaluation of dietary flaxseed intervention with a focus on toxicologically relevant molecular gene targets. Gene expression levels in lung tissues were analyzed using a large-scale array whereby 28,800 genes were evaluated.Results3,713 genes (12.8 %) were significantly (p < 0.05) differentially expressed, of which 2,088 had a >1.5-fold change. Genes affected by FS include those in protective pathways such as Phase I and Phase II.ConclusionsThe array studies have provided information on how FS modulates gene expression in lung and how they might be related to protective mechanisms. In addition, our study has confirmed that flaxseed is a nutritional supplement with potentially useful therapeutic applications in complementary and alternative (CAM) medicine especially in relation to treatment of lung disease.
Multi-task hidden Markov modeling of spectrogram feature from radar high-resolution range profiles
Authors: Pan Mian , Du Lan , Wang Penghui , Liu Hongwei , Bao Zheng 
Published: April 2012

AbstractIn radar high-resolution range profile (HRRP)-based statistical target recognition, one of the most challenging task is the feature extraction. This article utilizes spectrogram feature of HRRP data for improving the recognition performance, of which the spectrogram is a two-dimensional feature providing the variation of frequency domain feature with time domain feature. And then, a new radar HRRP target recognition method is presented via a truncated stick-breaking hidden Markov model (TSB-HMM). Moreover, multi-task learning (MTL) is employed, from which a full posterior distribution on the numbers of states associated with the targets can be inferred and the target-dependent states information are shared among multiple target-aspect frames of each target. The framework of TSB-HMM allows efficient variational Bayesian inference, of interest for large-scale problem. Experimental results for measured data show that the spectrogram feature has significant advantages over the time domain sample in both the recognition and rejection performance, and MTL provides a better recognition performance.