bluuebunny/crossref_metadata_2025_split huggingface dataset:
SOX11 expression correlates to promoter methylation and regulates tumor growth in hematopoietic malignancies
Authors: Gustavsson Elin , Sernbo Sandra , Andersson Elin , Brennan Donal J. , Dictor Michael , Jerkeman Mats , Borrebaeck Carl A. K. , Ek Sara 
Published: July 2010

Abstract

Background
The transcription factor SOX11 plays an important role in embryonic development of the central nervous system (CNS) and is expressed in the adult immature neuron but is normally not expressed in any other adult tissue. It has recently been reported to be implicated in various malignant neoplasms, including several lymphoproliferative diseases, by its specific expression and in some cases correlation to prognosis. SOX11 has been shown to prevent gliomagenesis in vivo but the causes and consequences of aberrant expression of SOX11 outside the CNS remain unexplained.

Results
We now show the first function of SOX11 in lymphoproliferative diseases, by demonstrating in vitro its direct involvement in growth regulation, as assessed by siRNA-mediated silencing and ectopic overexpression in hematopoietic malignancies. Gene Chip analysis identified cell cycle regulatory pathways, including Rb-E2F, to be associated with SOX11-induced growth reduction. Furthermore, promoter analysis revealed that SOX11 is silenced through DNA methylation in B cell lymphomas, suggesting that its regulation is epigenetically controlled.

Conclusions
The data show that SOX11 is not a bystander but an active and central regulator of cellular growth, as both siRNA-mediated knock-down and ectopic overexpression of SOX11 resulted in altered proliferation. Thus, these data demonstrate a tumor suppressor function for SOX11 in hematopoietic malignancies and revealed a potential epigenetic regulation of this developmentally involved gene.
Extensive analysis of D7S486 in primary gastric cancer supports TESTIN as a candidate tumor suppressor gene
Authors: Ma Haiqing , Weng Desheng , Chen Yibing , Huang Wei , Pan Ke , Wang Hui , Sun Jiancong , Wang Qijing , Zhou Zhiwei , Wang Huiyun , Xia Jianchuan 
Published: July 2010

AbstractBackgroundHigh frequency of loss of heterozygosity (LOH) was found at D7S486 in primary gastric cancer (GC). And we found a high frequency of LOH region on 7q31 in primary GC from China, and identified D7S486 to be the most frequent LOH locus. This study was aimed to determine what genes were affected by the LOH and served as tumor suppressor genes (TSGs) in this region. Here, a high-throughput single nucleotide polymorphisms (SNPs) microarray fabricated in-house was used to analyze the LOH status around D7S486 on 7q31 in 75 patients with primary GC. Western blot, immunohistochemistry, and RT-PCR were used to assess the protein and mRNA expression of TESTIN (TES) in 50 and 140 primary GC samples, respectively. MTS assay was used to investigate the effect of TES overexpression on the proliferation of GC cell lines. Mutation and methylation analysis were performed to explore possible mechanisms of TES inactivation in GC.ResultsLOH analysis discovered five candidate genes (ST7,FOXP2,MDFIC,TESandCAV1) whose frequencies of LOH were higher than 30%. However, onlyTESshowed the potential to be a TSG associated with GC. Among 140 pairs of GC samples, decreasedTESmRNA level was found in 96 (68.6%) tumor tissues when compared with matched non-tumor tissues (p< 0.001). Also, reduced TES protein level was detected in 36 (72.0%) of all 50 tumor tissues by Western blot (p= 0.001). In addition, immunohistochemical staining result was in agreement with that of RT-PCR and Western blot. Down regulation of TES was shown to be correlated with tumor differentiation (p= 0.035) and prognosis (p= 0.035, log-rank test). Its overexpression inhibited the growth of three GC cell lines. Hypermethylation ofTESpromoter was a frequent event in primary GC and GC cell lines. However, no specific gene mutation was observed in the coding region of theTESgene.ConclusionsCollectively, all results support the role ofTESas a TSG in gastric carcinogenesis and thatTESis inactivated primarily by LOH and CpG island methylation.
Proteomic analysis of differentially expressed proteins in Penaeus monodon hemocytes after Vibrio harveyi infection
Authors: Somboonwiwat Kunlaya , Chaikeeratisak Vorrapon , Wang Hao-Ching , Fang Lo Chu , Tassanakajon Anchalee 
Published: July 2010

Abstract

Background
Viral and bacterial diseases can cause mass mortalities in commercial shrimp aquaculture. In contrast to studies on the antiviral response, the responses of shrimps to bacterial infections by high throughput techniques have been reported only at the transcriptional level and not at the translational level. In this study, a proteomic analysis of shrimp hemocytes to identify differentially expressed proteins in response to a luminous bacterium Vibrio harveyi was evaluated for its feasibility and is reported for the first time.

Results
The two-dimensional gel electrophoresis (2-DE) patterns of the hemocyte proteins from the unchallenged and V. harveyi challenged shrimp, Penaeus monodon, at 24 and 48 h post infection were compared. From this, 27 differentially expressed protein spots, and a further 12 weakly to non-differentially regulated control spots, were selected for further analyses by the LC-ESI-MS/MS. The 21 differentially expressed proteins that could be identified by homologous annotation were comprised of proteins that are directly involved in the host defense responses, such as hemocyanin, prophenoloxidase, serine proteinase-like protein, heat shock protein 90 and alpha-2-macroglobulin, and those involved in signal transduction, such as the14-3-3 protein epsilon and calmodulin. Western blot analysis confirmed the up-regulation of hemocyanin expression upon bacterial infection. The expression of the selected proteins which were the representatives of the down-regulated proteins (the 14-3-3 protein epsilon and alpha-2-macroglobulin) and of the up-regulated proteins (hemocyanin) was further assessed at the transcription level using real-time RT-PCR.

Conclusions
This work suggests the usefulness of a proteomic approach to the study of shrimp immunity and revealed hemocyte proteins whose expression were up regulated upon V. harveyi infection such as hemocyanin, arginine kinase and down regulated such as alpha-2-macroglobulin, calmodulin and 14-3-3 protein epsilon. The information is useful for understanding the immune system of shrimp against pathogenic bacteria.
Reliability of 95% confidence interval revealed by expected quality-of-life scores: an example of nasopharyngeal carcinoma patients after radiotherapy using EORTC QLQ-C 30
Authors: Chien Tsair-Wei , Lin Shun-Jin , Wang Wen-Chung , Leung Henry WC , Lai Wen-Pin , Chan Agnes LF 
Published: July 2010

Abstract

Background
Many researchers use observed questionnaire scores to evaluate score reliability and to make conclusions and inferences regarding quality-of-life outcomes. The amount of false alarms from medical diagnoses that would be avoided if observed scores were substituted with expected scores is interesting, and understanding these differences is important for the care of cancer patients. Using expected scores to estimate the reliability of 95% confidence intervals (CIs) is rarely reported in published papers. We investigated the reliability of patient responses to a quality-of-life questionnaire and made recommendations for future studies of the quality of life of patients.

Methods
A total of 115 patients completed the EORTC core questionnaire QLQ-C30 (version 3) after radiotherapy. The observed response scores, assumed to be one-dimensional, were summed and transformed into expected scores using the Rasch rating scale model with WINSTEPS software. A series of simulations was performed using a unified bootstrap procedure after manipulating scenarios with different questionnaire lengths and patient numbers to estimate the reliability at 95% confidence intervals. Skewness analyses of the 95% CIs were compared to detect different effects between groups according to the two data sets of observed and expected response scores.

Results
We found that (1) it is necessary to report CIs for reliability and skewness coefficients in papers; (2) data derived from expected response scores are preferable to making inferences; and (3) visual representations displaying the 95% CIs of skewness values applied to item-by-item analyses can provide a useful interpretation of quality-of-life outcomes.

Conclusion
Reliability coefficients can be reported with 95% CIs by statistical software to evaluate the internal consistency of respondent scores on questionnaire items. The SPSS syntax procedures for estimating the reliability of the 95% CI, expected score generation and visual skewness analyses are demonstrated in this study. We recommend that effect sizes such as a 95% CI be reported along with p values reporting significant differences in quality-of-life studies.
Solitary colonic metastasis from renal cell carcinoma presenting as a surgical emergency nine years post-nephrectomy
Authors: Jadav Alka M , Thrumurthy Sri G , DeSousa Bernard A 
Published: July 2010

Abstract
Late colonic metastasis following curative surgery for renal cell carcinoma has rarely been described. We present the first reported case of solitary colonic renal cell carcinoma metastasis presenting as an intra-abdominal bleed, nine years post-nephrectomy.
Proto-oncogene c-erbB2 initiates rat primordial follicle growth via PKC and MAPK pathways
Authors: Li-Ping Zheng , Da-Lei Zhang , Jian Huang , Liang-Quan Xu , Ai-Xia Xu , Xiao-Yu Du , Dan-Feng Tang , Yue-Hui Zheng 
Published: July 2010

Abstract

Background
c-erbB2, a proto-oncogene coding epidermal growth factor receptor-like receptor, also as a chemosensitivity/prognosis marker for gynecologic cancer, may be involved in initiation of growth of rat primordial follicles. The aim of the present study is to investigate the role and signal pathway of c-erbB2 in onset of rat primordial follicle development.

Methods
The expression of c-erbB2 mRNA and protein in neonatal ovaries cultured 4 and 8 days with/without epidermal growth factor (EGF) were examined by in situ hybridization, RT-PCR and western blot. The function of c-erbB2 in the primordial folliculogenesis was abolished by small interfering RNA transfection. Furthermore, MAPK inhibitor PD98059 and PKC inhibitor calphostin were used to explore the possible signaling pathway of c-erbB2 in primordial folliculogenesis.

Results
The results showed that c-erbB2 mRNA was expressed in ooplasm and the expression of c-erbB2 decreased after transfection with c-erbB2 siRNA. Treatment with EGF at 50 ng/ml significantly increased c-erbB2 expression and primary and secondary follicle formation in ovaries. However, this augmenting effect was remarkably inhibited by c-erbB2 siRNA transfection. Furthermore, folliculogenesis offset was blocked by calphostin (5 × 10(-4) mmol/L) and PD98059 (5 × 10(-2) mmol/L), but both did not down-regulate c-erbB2 expression. In contrast, the expressions of p-ERK and p-PKC were decreased obviously by c-erbB2 siRNA transfection.

Conclusions
c-erbB2 initiates rat primordial follicle growth via PKC and MAPK pathways, suggesting an important role of c-erbB2 in rat primordial follicle initiation and development.
Serious limitations of the QTL/Microarray approach for QTL gene discovery
Authors: Verdugo Ricardo A , Farber Charles R , Warden Craig H , Medrano Juan F 
Published: July 2010

Abstract

Background
It has been proposed that the use of gene expression microarrays in nonrecombinant parental or congenic strains can accelerate the process of isolating individual genes underlying quantitative trait loci (QTL). However, the effectiveness of this approach has not been assessed.

Results
Thirty-seven studies that have implemented the QTL/microarray approach in rodents were reviewed. About 30% of studies showed enrichment for QTL candidates, mostly in comparisons between congenic and background strains. Three studies led to the identification of an underlying QTL gene. To complement the literature results, a microarray experiment was performed using three mouse congenic strains isolating the effects of at least 25 biometric QTL. Results show that genes in the congenic donor regions were preferentially selected. However, within donor regions, the distribution of differentially expressed genes was homogeneous once gene density was accounted for. Genes within identical-by-descent (IBD) regions were less likely to be differentially expressed in chromosome 2, but not in chromosomes 11 and 17. Furthermore, expression of QTL regulated in cis (cis eQTL) showed higher expression in the background genotype, which was partially explained by the presence of single nucleotide polymorphisms (SNP).

Conclusions
The literature shows limited successes from the QTL/microarray approach to identify QTL genes. Our own results from microarray profiling of three congenic strains revealed a strong tendency to select cis-eQTL over trans-eQTL. IBD regions had little effect on rate of differential expression, and we provide several reasons why IBD should not be used to discard eQTL candidates. In addition, mismatch probes produced false cis-eQTL that could not be completely removed with the current strains genotypes and low probe density microarrays. The reviewed studies did not account for lack of coverage from the platforms used and therefore removed genes that were not tested. Together, our results explain the tendency to report QTL candidates as differentially expressed and indicate that the utility of the QTL/microarray as currently implemented is limited. Alternatives are proposed that make use of microarray data from multiple experiments to overcome the outlined limitations.
Stem cell proliferation during in vitro development of the model cestode Mesocestoides corti from larva to adult worm
Authors: Koziol Uriel , Domínguez María F , Marín Mónica , Kun Alejandra , Castillo Estela 
Published: July 2010

Abstract

Background
In free-living flatworms somatic differentiated cells do not divide, and a separate population of stem cells (called neoblasts) is responsible for cell proliferation and renewal. In cestodes, there is evidence that similar mechanisms of cell renewal exist.

Results
In this work, we have characterized proliferative cells during the development of the model cestode Mesocestoides corti from larva (tetrathyridium) to young segmented worm. This was done by two complementary strategies with congruent results: characterizing cells in S phase and their progeny by incorporation of 5-bromo-2'-deoxyuridine, and characterizing cells in M phase by arresting mitotic cells with colchicine and studying their morphology and distribution. Proliferative cells are localized only in the inner parenchyma, particularly in close proximity to the inner muscle layer, but not in the cortical parenchyma nor in the sub-tegumental tissue. After proliferation some of these cells migrate to the outer regions were they differentiate. In the larvae, proliferative cells are more abundant in the anterior regions (scolex and neck), and their number diminishes in an antero-posterior way. During the development of adult segments periodic accumulation of proliferative cells are observed, including a central mass of cells that constitutes the genital primordium, which grows at least in part due to in situ proliferation. In later segments, the inner cells of genital primordia cease to proliferate and adopt a compact distribution, and proliferative cells are also found in the testes primordia.

Conclusions
Proliferative cells have a characteristic localization and morphology throughout development from larva to adult of Mesocestoides corti, which is similar, and probably evolutionary conserved, to that described in other model cestodes. The characteristics of proliferative cells suggest that these consist of undifferentiated stem cells.
The timing of perinatal hypoxia/ischemia events in term neonates: a retrospective autopsy study. HSPs, ORP-150 and COX2 are reliable markers to classify acute, perinatal events
Authors: Riezzo Irene , Neri Margherita , De Stefano Francesco , Fulcheri Ezio , Ventura Francesco , Pomara Cristoforo , Rabozzi Roberto , Turillazzi Emanuela , Fineschi Vittorio 
Published: July 2010

AbstractBackgroundThe understanding of the cellular responses implicated in perinatal brain damages and the characterization of the various mechanisms involved might open new horizons for understanding the time of onset of a brain hypoxic-ischemic lesion and for effective therapeutic strategies.MethodsWe performed an immunohistochemical investigation on brain and brainstem sections of 47 peripartum deaths. The gradation and localization of the expression of antibodies such as TNFα, IL-1β, IL-6, HSPs, β APP, anti-TrypH, GAP43, GFAP, COX2, ORP-150, could be correlated with an hypoxic-ischemic damage to document a significant correlation between response and the time of onset acute (≤8 hs) or non-acute (≥8 hs ≤48 hs).Results and DiscussionsIn non-acute cases HSP70 reaction was prominent in the neuron cytoplasm, while in acute cases a mild reaction was evident in sporadic fields. HSP90 exhibited a similar pattern of positivity as HSP70. In acute group, ORP150 expressed an intense reaction showing a granular pattern in the cytoplasm of the neurons in the cortex of the infarcted areas. In non-acute group the positive reaction was more intense in astrocytes and less extended in neurons. COX2 reaction exhibited the strongest positive reaction in the neuronal cell bodies of acute cases, while a immunolabeling was prominent in the glial cytoplasm in the non-acute cases.ConclusionsChaperones HSP70 and 90, ORP-150 reaction, and COX2 protein, have provided very interesting results. These results would suggest to the clinicians to extend the differential diagnosis of a too large perinatal hypoxic-ischemic insult category to delineate a more accurate chronological judgement.
The instantaneous helical axis of the subtalar and talocrural joints: a non‐invasive in vivo dynamic study
Authors: Sheehan Frances T 
Published: July 2010

AbstractBackgroundAn understanding of rear‐foot (talocrural and subtalar joints) kinematics is critical for diagnosing foot pathologies, designing total ankle implants, treating rear‐foot injuries and quantifying gait abnormalities. The majority of kinematic data available have been acquired through static cadaver work or passive in vivo studies. The applicability of these data to dynamic in vivo situations remains unknown. Thus, the purpose of this study was to fully quantify subtalar, talocrural and calcaneal‐tibial in vivo kinematics in terms of the instantaneous helical axis (IHA) in twenty‐five healthy ankles during a volitional activity that simulated single‐leg toe‐raises with partial‐weight support, requiring active muscle control.MethodsSubjects were each placed supine in a 1.5 T MRI and asked to repeat this simulated toe‐raise while a full sagittal‐cine‐phase contrast (dynamic) MRI dataset was acquired. From the cine‐phase contrast velocity a full kinematic description for each joint was derived.ResultsNearly all motion quantified at the calcaneal‐tibial joint was attributable to the talocrural joint. The subtalar IHA orientation and position were highly variable; whereas, the talocrural IHA orientation and position were extremely consistent.ConclusionThe talocrural was well described by the IHA and could be modeled as a fixed‐hinge joint, whereas the subtalar could not be.
Low cholesterol? Don't brag yet … hypocholesterolemia blunts HAART effectiveness: a longitudinal study
Authors: Míguez María Jose , Lewis John E , Bryant Vaughn E , Rosenberg Rhonda , Burbano Ximena , Fishman Joel , Asthana Deshratn , Duan Rui , Madhavan Nair , Malow Robert M 
Published: July 2010

BackgroundIn vitro studies suggest that reducing cholesterol inhibits HIV replication. However, this effect may not hold in vivo, where other factors, such as cholesterol's immunomodulatory properties, may interact.MethodsFasting blood samples were obtained on 165 people living with HIV at baseline and after 24 weeks on highly active antiretroviral therapy (HAART). Participants were classified as hypocholesterolemic (HypoCHL; <150 mg/dl) or non‐HypoCHL (>150 mg/dl) and were compared on viro‐immune outcomes.ResultsAt baseline, participants with HypoCHL (40%) exhibited lower CD4 (197 ± 181 vs. 295 ± 191 cells/mm3, p = 0.02) and CD8 (823 ± 448 vs. 1194 ± 598 cells/mm3, p = 0.001) counts and were more likely to have detectable viral loads (OR = 3.5, p = 0.01) than non‐HypoCHL controls. After HAART, participants with HypoCHL were twice as likely to experience a virological failure >400 copies (95% CI 1‐2.6, p = 0.05) and to exhibit <200 CD4 (95% CI 1.03‐2.9, p = 0.04) compared with non‐HypoCHL. Low thymic output was related to poorer CD4 cell response in HypoCHL subjects. Analyses suggest a dose‐response relationship with every increase of 50 mg/dl in cholesterol related to a parallel rise of 50 CD4 cells.ConclusionsThe study implicates, for the first time, HypoCHL with impaired HAART effectiveness, including limited CD4 repletion by the thymus and suboptimal viral clearance.
Pharmacoproteomic study of the effects of chondroitin and glucosamine sulfate on human articular chondrocytes
Authors: Calamia Valentina , Ruiz-Romero Cristina , Rocha Beatriz , Fernández-Puente Patricia , Mateos Jesús , Montell Eulàlia , Vergés Josep , Blanco Francisco J 
Published: July 2010

Abstract
Introduction
Chondroitin sulfate (CS) and glucosamine sulfate (GS) are symptomatic slow-acting drugs for osteoarthritis (OA) widely used in clinic. Despite their widespread use, knowledge of the specific molecular mechanisms of their action is limited. The aim of this work is to explore the utility of a pharmacoproteomic approach for the identification of specific molecules involved in the pharmacological effect of GS and CS.

Methods
Chondrocytes obtained from three healthy donors were treated with GS 10 mM and/or CS 200 μg/mL, and then stimulated with interleukin-1β (IL-1β) 10 ng/mL. Whole cell proteins were isolated 24 hours later and resolved by two-dimensional electrophoresis. The gels were stained with SYPRORuby. Modulated proteins were identified by matrix-assisted laser desorption/ionization time-of-flight (MALDI-TOF/TOF) mass spectrometry. Real-time PCR and Western blot analyses were performed to validate our results.

Results
A total of 31 different proteins were altered by GS or/and CS treatment when compared to control. Regarding their predicted biological function, 35% of the proteins modulated by GS are involved in signal transduction pathways, 15% in redox and stress response, and 25% in protein synthesis and folding processes. Interestingly, CS affects mainly energy production (31%) and metabolic pathways (13%), decreasing the expression levels of ten proteins. The chaperone GRP78 was found to be remarkably increased by GS alone and in combination with CS, a fact that unveils a putative mechanism for the reported anti-inflammatory effect of GS in OA. On the other hand, the antioxidant enzyme superoxide dismutase 2 (SOD2) was significantly decreased by both drugs and synergistically by their combination, thus suggesting a drug-induced decrease of the oxidative stress caused by IL-1β in chondrocytes.

Conclusions
CS and GS differentially modulate the proteomic profile of human chondrocytes. This pharmacoproteomic approach unravels the complex intracellular mechanisms that are modulated by these drugs on IL1β-stimulated human articular chondrocytes.