bluuebunny/crossref_metadata_2025_split huggingface dataset:
Haploinsufficiency for ribosomal protein genes causes selective activation of p53 in human erythroid progenitor cells
Authors: Dutt Shilpee , Narla Anupama , Lin Katherine , Mullally Ann , Abayasekara Nirmalee , Megerdichian Christine , Wilson Frederick H. , Currie Treeve , Khanna-Gupta Arati , Berliner Nancy , Kutok Jeffery L. , Ebert Benjamin L. 
Published: November 2010

AbstractHaploinsufficiency for ribosomal protein genes has been implicated in the pathophysiology of Diamond-Blackfan anemia (DBA) and the 5q− syndrome, a subtype of myelodysplastic syndrome. The p53 pathway is activated by ribosome dysfunction, but the molecular basis for selective impairment of the erythroid lineage in disorders of ribosome function has not been determined. We found that p53 accumulates selectively in the erythroid lineage in primary human hematopoietic progenitor cells after expression of shRNAs targeting RPS14, the ribosomal protein gene deleted in the 5q− syndrome, or RPS19, the most commonly mutated gene in DBA. Induction of p53 led to lineage-specific accumulation of p21 and consequent cell cycle arrest in erythroid progenitor cells. Pharmacologic inhibition of p53 rescued the erythroid defect, whereas nutlin-3, a compound that activates p53 through inhibition of HDM2, selectively impaired erythropoiesis. In bone marrow biopsies from patients with DBA or del(5q) myelodysplastic syndrome, we found an accumulation of nuclear p53 staining in erythroid progenitor cells that was not present in control samples. Our findings indicate that the erythroid lineage has a low threshold for the induction of p53, providing a basis for the failure of erythropoiesis in the 5q− syndrome, DBA, and perhaps other bone marrow failure syndromes.
Algorithm-driven Artifacts in median polish summarization of Microarray data
Authors: Giorgi Federico M , Bolger Anthony M , Lohse Marc , Usadel Bjoern 
Published: November 2010

Abstract

Background
High-throughput measurement of transcript intensities using Affymetrix type oligonucleotide microarrays has produced a massive quantity of data during the last decade. Different preprocessing techniques exist to convert the raw signal intensities measured by these chips into gene expression estimates. Although these techniques have been widely benchmarked in the context of differential gene expression analysis, there are only few examples where their performance has been assessed in respect to coexpression-based studies such as sample classification.

Results
In the present paper we benchmark the three most used normalization procedures (MAS5, RMA and GCRMA) in the context of inter-array correlation analysis, confirming and extending the finding that RMA and GCRMA consistently overestimate sample similarity upon normalization. We determine that median polish summarization is responsible for generating a large proportion of these over-similarity artifacts. Furthermore, we show that most affected probesets show also internal signal disagreement, and tend to be composed by individual probes hitting different gene transcripts. We finally provide a correction to the RMA/GCRMA summarization procedure that massively reduces inter-array correlation artifacts, without affecting the detection of differentially expressed genes.

Conclusions
We propose tRMA as a modification of RMA to normalize microarray experiments for correlation-based analysis.
Genes regulated by the Escherichia coli SOS repressor LexA exhibit heterogenous expression
Authors: Kamenšek Simona , Podlesek Zdravko , Gillor Osnat , Žgur-Bertok Darja 
Published: November 2010

Abstract

Background
Phenotypic heterogeneity may ensure that a small fraction of a population survives environmental perturbations or may result in lysis in a subpopulation, to increase the survival of siblings. Genes involved in DNA repair and population dynamics play key roles in rapid responses to environmental conditions. In Escherichia coli the transcriptional repressor LexA controls a coordinated cellular response to DNA damage designated the SOS response. Expression of LexA regulated genes, e.g. colicin encoding genes, recA, lexA and umuDC, was examined utilizing transcription fusions with the promoterless gfp at the single cell level.

Results
The investigated LexA regulated genes exhibited heterogeneity, as only in a small fraction of the population more intense fluorescence was observed. Unlike recA and lexA, the pore forming and nuclease colicin activity genes as well as umuDC, exhibited no basal level activity. However, in a lexA defective strain high level expression of the gene fusions was observed in the large majority of the cells. All of the investigated genes were expressed in a recA defective strain, albeit at lower levels, revealing expression in the absence of a spontaneous SOS response. In addition, the simultaneous expression of cka, encoding the pore forming colicin K, and lexA, investigated at the single cell level revealed high level expression of only cka in rare individual cells.

Conclusion
LexA regulated genes exhibit phenotypic heterogeneity as high level expression is observed in only a small subpopulation of cells. Heterogenous expression is established primarily by stochastic factors and the binding affinity of LexA to SOS boxes.
Human papillomavirus (HPV) types 16, 18, 31, 45 DNA loads and HPV-16 integration in persistent and transient infections in young women
Authors: Ramanakumar Agnihotram V , Goncalves Otelinda , Richardson Harriet , Tellier Pierre , Ferenczy Alex , Coutlée François , Franco Eduardo L 
Published: November 2010

AbstractBackgroundHPV burden is a predictor for high-grade cervical intraepithelial neoplasia and cancer. The natural history of HPV load in young women being recently exposed to HPV is described in this paper.MethodsA total of 636 female university students were followed for 2 years. Cervical specimens with HPV-16, -18, -31, or -45 DNA by consensus PCR were further evaluated with type-specific and β-globin real-time PCR assays. Proportional hazards regression was used to estimate hazard ratios (HR) of infection clearance. Generalized estimating equations assessed whether HPV loads was predictive of HPV infection at the subsequent visit.ResultsHPV loads were consistently higher among women <25 years old, and those who had multiple sex partners, multiple HPV type infections and smokers. HPV-16 integration was encountered only in one sample. Infection clearance was faster among women at lower tertiles of HPV-16 (HR = 2.8, 95%CI: 1.0-8.1), HPV-18 (HR = 3.5, 95%CI: 1.1-11.2) or combined (HR = 2.4, 95%CI: 1.8-6.2) DNA loads. The relationship between HPV-16 and HPV-18 DNA loads and infection clearance followed a clear dose-response pattern, after adjusting for age and number of sexual partners. GEE Odds Ratios for HPV persistence of the middle and upper tertiles relative to the lower tertile were 2.7 and 3.0 for HPV-16 and 3.8 and 39.1 for HPV-18, respectively. There was no association between HPV-31 or -45 DNA loads and persistence.ConclusionsThe association between HPV load and persistence is not uniform across high-risk genital genotypes. HPV-16 integration was only rarely demonstrated in young women.
Sequencing of DC-SIGN promoter indicates an association between promoter variation and risk of nasopharyngeal carcinoma in cantonese
Authors: Xu Ya-Fei , Liu Wan-Li , Dong Ju-Qin , Liu Wen-Sheng , Feng Qi-Sheng , Chen Li-Zhen , Zeng Yi-Xin , Zeng Mu-Sheng , Jia Wei-Hua 
Published: November 2010

AbstractBackgroundThe dendritic cell-specific intercellular adhesion molecule 3 grabbing non-integrin (DC-SIGN) is an important pathogen recognition receptor of the innate immune system.DC-SIGNpromoter variants play important role in the susceptibility to various infectious diseases. Nasopharyngeal carcinoma (NPC) is a malignancy that is common in southern China and whetherDC-SIGNpromoter variants have effects on susceptibility to NPC is still unknown. The aim of this study is to ascertain the potential involvement ofDC-SIGNpromoter single nucleotide polymorphisms (SNPs) in NPC susceptibility.MethodsWe conducted a case control study based on Cantonese population including 444 NPC patients and 464 controls matched on age and sex. The 1041 bp ofDC-SIGNpromoter region was directly sequenced for all samples. Sequence alignment and SNP search were inspected using DNAStar analysis programs and haplotype frequencies were estimated in Haploview V 4.0. The associations between the SNPs and the risk of NPC were analyzed using chi-square test and non-conditional logistic regression analysis with SPSS 13.0 software.ResultsA total of six variants were observed in theDC-SIGNpromoter region andDC-SIGN-139 GG and -939 AA were significantly associated with NPC risk with adjusted Odds Ratios (ORs) of 2.10 (95% confidence interval [CI] = 1.23-3.59;P= 0.006) and 2.52 (1.29-4.93;P= 0.007) respectively and subjects carrying the risk alleleDC-SIGN-871 G had 1.47-fold (95% CI = 1.14-1.90) increased risks of developing NPC (P= 0.003). Haplotype analysis revealed that h1 'AAAG' was significantly associated with protection against NPC (OR = 0.69;P= 0.0002) and the association was still significant when using 1000 permutation test runs (P= 0.001).ConclusionsOur study indicated thatDC-SIGNpromoter variants appear to be involved in the susceptibility to NPC and the detailed mechanism of this effect need further studies.
SpineCor treatment for Juvenile Idiopathic Scoliosis: SOSORT award 2010 winner
Authors: Coillard Christine , Circo Alin B , Rivard Charles H 
Published: November 2010

AbstractIntroductionJuvenile idiopathic scoliosis is a condition used to describe patients who are least 4 years of age but younger than 10 when the deformity is first identified. In these patients, the condition is usually progressive and those that are diagnosed at five years or younger have a high chance of progression to a large curve, with additional pulmonary and cardiac complications. The main form of conservative treatment for juvenile scoliosis is the use of a bracing system. This prospective interventional study was conducted to evaluate the effectiveness of the Dynamic SpineCor orthosis for juvenile idiopathic scoliosis as well as to evaluate the stability of the spine after the weaning point.Material and MethodsFor this study, 150 juvenile patients were treated by the SpineCor orthosis between 1993 and 2009. Of these, 67 patients had a definite outcome and 83 are still actively being treated. To determine the effectiveness of the brace theOUTCOMEcriteria recommended by the SRS was used.ResultsThe results from our study showed that of the 67 patients with a definite outcome, 32.9% corrected their Cobb angle by at least 5° and 10.5% had a stabilization of their Cobb angle. Within the patients with a definite outcome, 37.3% of patients where recommended for surgery before authorized end of treatment. For this group of patients, surgery was postponed. Looking at the stability of the curves 2 years after the end of the treatment, we found 12.5% of the patients continued their correction without the brace being used and 71.4% remained stable.DiscussionFrom our study we can clearly see that the effectiveness of the SpineCor orthosis in obtaining and maintaining the neuromuscular integration of the corrective movement can be achieved effectively for juvenile patients. Over 75% of all patients that finished the treatment had remained stable with a few continuing to correct their Cobb angle after the use of the SpineCor orthosis was discontinued.ConclusionOur conclusion from this study is that the SpineCor orthosis is a very effective method of treatment of juvenile idiopathic scoliosis. The results obtained also indicate that treatment outcomes are better with early bracing. Most encouraging perhaps is the fact that the positive outcome appears to be maintained in the long term, and that surgery can be avoided or at least postponed.
Prevalence of Metabolic Syndrome and its influence on microvascular complications in the Indian population with Type 2 Diabetes Mellitus. Sankara Nethralaya Diabetic Retinopathy Epidemiology And Molecular Genetic Study (SN-DREAMS, report 14)
Authors: Raman Rajiv , Gupta Aditi , Pal Swakshyar S , Ganesan Suganeswari , Venkatesh Kadri , Kulothungan Vaitheeswaran , Sharma Tarun 
Published: November 2010

Abstract

Background
The Metabolic syndrome (MS) consists of central obesity, glucose intolerance, hyperinsulinemia, low high density lipoproteins, high triglycerides and hypertension. Different studies have observed that MS causes microvascular complications in patients with type 2 diabetes. The aim of the study was to find out the prevalence of MS in the Indian population with type 2 diabetes mellitus in relation to gender, duration of diabetes, and to evaluate the influence of MS and its individual components on microvascular complications such as diabetic retinopathy, diabetic nephropathy and diabetic neuropathy.

Methods
A population-based cross sectional survey was conducted with 1414 patients having type 2 diabetes mellitus. The International Diabetes Federation (IDF) criteria were used to identify the metabolic syndrome. Diabetic retinopathy was graded using the stereoscopic digital fundus photography. Neuropathy was assessed by measuring the vibration perception threshold through a sensitometer. Nephropathy was diagnosed by the presence of microalbuminuria in the first morning urine sample.

Results
The age and gender adjusted prevalence of MS, using the IDF criteria, in the South Indian population was 73.3%. The prevalence was higher in women (83.3%), compared to men (65.3%). In subjects with diabetes mellitus, without and with MS, the prevalence of retinopathy was 21.3% and 16.9% (p = 0.057); prevalence of nephropathy was 20.5% and 18.0% (p = 0.296), and prevalence of neuropathy was17.2% and 19.4% (p = 0.353) respectively. Overall and in women, the clustering of MS components led to an increase in the prevalence of diabetic nephropathy. The prevalence of retinopathy and neuropathy in MS subjects, who had diabetes for < 10 years, was more in both men and women; it was more in women but not in men when the duration of diabetes varied from 11-20 years.

Conclusions
The association of MS with microangiopathies decreased with an increase in the duration of diabetes. MS behaved differently in men and women. It may need to be managed differently in the two groups.
A Western Diet Increases Serotonin Availability in Rat Small Intestine
Authors: Bertrand R. L. , Senadheera S. , Markus I. , Liu L. , Howitt L. , Chen H. , Murphy T. V. , Sandow S. L. , Bertrand P. P. 
Published: November 2010

Abstract
Diet-induced obesity is associated with changes in gastrointestinal function and induction of a mild inflammatory state. Serotonin (5-HT) containing enterochromaffin (EC) cells within the intestine respond to nutrients and are altered by inflammation. Thus, our aim was to characterize the uptake and release of 5-HT from EC cells of the rat ileum in a physiologically relevant model of diet-induced obesity. In chow-fed (CF) and Western diet–fed (WD) rats electrochemical methods were used to measure compression evoked (peak) and steady state (SS) 5-HT levels with fluoxetine used to block the serotonin reuptake transporter (SERT). The levels of mRNA for tryptophan hydroxylase 1 (TPH1) and SERT were determined by quantitative PCR, while EC cell numbers were determined immunohistochemically. In WD rats, the levels of 5-HT were significantly increased (SS: 19.2±3.7 μm; peak: 73.5±14.1 μm) compared with CF rats (SS: 12.3±1.8 μm; peak: 32.2±7.2 μm), while SERT-dependent uptake of 5-HT was reduced (peak WD: 108% of control versus peak CF: 212% control). In WD rats, there was a significant increase in TPH1 mRNA, a decrease in SERT mRNA and protein, and an increase in EC cells. In conclusion, our data show that foods typical of a Western diet are associated with an increased 5-HT availability in the rat ileum. Increased 5-HT availability is driven by the up-regulation of 5-HT synthesis genes, decreased re-uptake of 5-HT, and increased numbers and/or 5-HT content of EC cells which are likely to cause altered intestinal motility and sensation in vivo.
Developmental Time Course of Estradiol, Testosterone, and Dihydrotestosterone Levels in Discrete Regions of Male and Female Rat Brain
Authors: Konkle Anne T. M. , McCarthy Margaret M. 
Published: November 2010

AbstractThe prevailing view of sexual differentiation of mammalian brain is that androgen synthesized in the fetal and neonatal testis and aromatized centrally during a perinatal sensitive period is the sole source of brain estradiol and the primary determinant of sex differences. Subregions of the diencephalon are among the most sexually dimorphic in the brain, and there are well-established sex differences in the amount of testosterone and estradiol measured in the hypothalamus and preoptic area during the perinatal period. We previously reported unexpectedly high estradiol in the hippocampus and cortex of both male and female newborn rat. This prompted a thorough investigation of the developmental profile of steroids in the rat brain using RIA to quantify the level of estradiol, testosterone, and dihydrotestosterone in discrete subregions of the brain from embryonic d 19 to adulthood. Plasma estradiol levels from individual animals were assessed when sufficient sample was available. A significant sex difference in hypothalamic testosterone prior to birth was consistent with previous findings. Postnatally, there was a distinct pattern of changing steroid concentrations in each brain region, and these were unrelated to circulating steroid. Removal of the gonads and adrenals at birth did not significantly reduce steroids in any brain region assayed 3 d later. Aromatase activity was detectable in all brain areas at birth, and the difference in activity level paralleled the observed regional differences in estradiol content. Based on these findings, we propose that steroidogenesis in the brain, independent of peripherally derived precursors, may play a critical role in mammalian brain development of both sexes, beyond the establishment of sex differences.
Clustering of Lipid Rafts in Plasma Membranes by Hybrid Liposomes for Leukemia Cells along with Apoptosis
Authors: Komizu Yuji , Nakata Sayuri , Goto Koichi , Matsumoto Yoko , Ueoka Ryuichi 
Published: November 2010

Abstract
Clustering of lipid rafts in plasma membranes by hybrid liposomes (HL-23) composed of l-α-dimyristoylphosphatidylcholine (DMPC) and polyoxyethylene(23) dodecyl ether (C12(EO)23) for human leukemia HL-60 cells was observed for the first time. It was suggested that the induction of apoptosis by HL-23 could be related to an increase of membrane fluidity and the formation of lipid rafts in the plasma membranes of HL-60 cells.
Fluoro-substituted Phenyleneethynylenes: Acetylenic n-Type Organic Semiconductors
Authors: Matsuo Daisuke , Yang Xin , Hamada Akiko , Morimoto Kyo , Kato Takuji , Yahiro Masayuki , Adachi Chihaya , Orita Akihiro , Otera Junzo 
Published: November 2010

Abstract
Fluoro-substituted phenyleneethynylenes are synthesized by Sonogashira coupling and acetylide-nucleophilic substitution of fluorobenzenes. Fluoro-substitution of benzenes enables deep LUMO potential, and CF3-substitution provides high electron mobility in deposited film (μ = 5.5 × 10−2 cm2 V−1 s−1).
Clinical presentation and early care relationships in ‘poor‐me’ and ‘bad‐me’ paranoia
Authors: Morris Emma , Milner Philip , Trower Peter , Peters Emmanuelle 
Published: November 2010

Objective. To test the proposal that ‘poor‐me’ (PM) and ‘bad‐me’ (BM) paranoia can be differentiated in terms of (1) current emotional experience and presence of grandiose delusions and (2) early caregiving and threats to self‐construction. Method. Participants experiencing persecutory delusions were separated into PM (N= 21) and BM (N= 15) groups on the basis of perceived deservedness of the persecution. The groups were compared on measures examining grandiose delusions, shame and depression, parental care, and threats of alienation and insecurity. Results. As predicted, BM patients scored higher on shame and depression, and lower on grandiose delusions, than PM patients. BM patients reported higher levels of parental overprotection, but PM patients were not characterized by neglect, and the groups did not differ in type of threat to self‐construction. Conclusion. The two paranoia types were differentiated on symptomatic and emotional presentation, but predicted differences in early relationships and self‐construction were not fully supported.
In Situ Studies of Variant Selection During the α-β-α Phase Transformation in Zr-2.5Nb
Authors: Mosbrucker P. , Daymond M. R. , Holt R. A. 
Published: November 2010

Abstract
In situ phase transformation experiments have been carried out using neutron and synchrotron X-ray diffraction to monitor the texture evolution and establish the criteria for variant selection during the α→β→α phase transformation in Zr-2.5Nb. There is clear evidence of a strong variant selection occurring during the α→β transformation and a weaker variant selection during the β→α transformation. Further, comparing hot-worked specimens with those that have received additional cold-work revealed that cold-work introduced microstructural characteristics that inhibited the full development of the transformed texture seen in the hot-worked samples. A study of the effect of external biasing stresses during transformation was conducted. An external biasing stress was applied along the hoop axis during different components of the α→β→α transformation. An external stress during heating does not appear to significantly influence variant selection, at least for the stress magnitudes tested here, while an external stress during cooling did have some influence on the resultant texture.
Energy Based Laboratory Fatigue Failure Criteria for Asphalt Materials
Authors: Shen Shihui , Lu Xin 
Published: November 2010

Abstract
The definition of fatigue failure in the laboratory is not only an important but also a controversial issue. Researchers have developed a number of fatigue failure criteria, including the most traditional one, which defines failure at the cycle to 50 % initial modulus reduction. However, this definition is always challenged due to its lack of physical background. Recent studies showed that the dissipated energy ratio approach appears to be a favorable concept, which takes into account the fundamental dissipated energy evolution behavior of asphalt materials during a cyclic fatigue test. This paper conducted a review of three different energy based fatigue failure criteria and evaluated their applicability for fatigue data from asphalt binders and mixtures and under both stress and strain controlled loading modes. A macroscopic failure criterion is recommended, which is defined as the sudden change of the dissipated energy evolution curve and is consistently related to the beginning of macrocrack propagation. In addition, by comparing different failure criteria, the traditional 50 % initial modulus reduction criterion was found to have a strong correlation with energy based macroscopic fatigue failure for both mixtures and binders. It is thus suggested that the 50 % initial modulus reduction failure can be used as a simple but reasonable fatigue criterion, which indicates the transition from microcrack to macrocrack.