bluuebunny/crossref_metadata_2025_split huggingface dataset:
Transcription Factors Sp1 and Sp4 Regulate TRPV1 Gene Expression in Rat Sensory Neurons
Authors: Chu Catherine , Zavala Kathryn , Fahimi Atefeh , Lee Jessica , Xue Qing , Eilers Helge , Schumacher Mark A 
Published: June 2011

Background: The capsaicin receptor, transient receptor potential vanilloid type −1 (TRPV1) directs complex roles in signal transduction including the detection of noxious stimuli arising from cellular injury and inflammation. Under pathophysiologic conditions, TRPV1 mRNA and receptor protein expression are elevated in dorsal root ganglion (DRG) neurons for weeks to months and is associated with hyperalgesia. Building on our previous isolation of a promoter system for the rat TRPV1 gene, we investigated the proximal TRPV1 P2-promoter by first identifying candidate Sp1-like transcription factors bound in vivo to the P2-promoter using chromatin immunoprecipitation (ChIP) assay. We then performed deletion analysis of GC-box binding sites, and quantified promoter activity under conditions of Sp1 / Sp4 over-expression versus inhibition/knockdown. mRNA encoding Sp1, Sp4 and TRPV1 were quantified by qRT-PCR under conditions of Sp1/Sp4 over-expression or siRNA mediated knockdown in cultured DRG neurons. Results: Using ChIP analysis of DRG tissue, we demonstrated that Sp1 and Sp4 are bound to the candidate GC-box site region within the endogenous TRPV1 P2-promoter. Deletion of GC-box “a“ or “a + b” within the P2-promoter resulted in a complete loss of transcriptional activity indicating that GC-box “a“ was the critical site for promoter activation. Co-transfection of Sp1 increased P2-promoter activity in cultured DRG neurons whereas mithramycin-a, an inhibitor of Sp1-like function, dose dependently blocked NGF and Sp1-dependent promoter activity in PC12 cells. Co-transfection of siRNA directed against Sp1 or Sp4 decreased promoter activity in DRG neurons and NGF treated PC12 cells. Finally, electroporation of Sp1 or Sp4 cDNA into cultures of DRG neurons directed an increase in Sp1/Sp4 mRNA and importantly an increase in TRPV1 mRNA. Conversely, combined si-RNA directed knockdown of Sp1/Sp4 resulted in a decrease in TRPV1 mRNA. Conclusion: Based on these studies, we now propose a model of TRPV1 expression that is dependent on Sp1-like transcription factors with Sp4 playing a predominant role in activating TRPV1 RNA transcription in DRG neurons. Given that increases of TRPV1 expression have been implicated in a wide range of pathophysiologic states including persistent painful conditions, blockade of Sp1-like transcription factors represents a novel direction in therapeutic strategies.
Cell cycle and aging, morphogenesis, and response to stimuli genes are individualized biomarkers of glioblastoma progression and survival
Authors: Serão Nicola VL , Delfino Kristin R , Southey Bruce R , Beever Jonathan E , Rodriguez-Zas Sandra L 
Published: June 2011

Abstract

Background
Glioblastoma is a complex multifactorial disorder that has swift and devastating consequences. Few genes have been consistently identified as prognostic biomarkers of glioblastoma survival. The goal of this study was to identify general and clinical-dependent biomarker genes and biological processes of three complementary events: lifetime, overall and progression-free glioblastoma survival.

Methods
A novel analytical strategy was developed to identify general associations between the biomarkers and glioblastoma, and associations that depend on cohort groups, such as race, gender, and therapy. Gene network inference, cross-validation and functional analyses further supported the identified biomarkers.

Results
A total of 61, 47 and 60 gene expression profiles were significantly associated with lifetime, overall, and progression-free survival, respectively. The vast majority of these genes have been previously reported to be associated with glioblastoma (35, 24, and 35 genes, respectively) or with other cancers (10, 19, and 15 genes, respectively) and the rest (16, 4, and 10 genes, respectively) are novel associations. Pik3r1, E2f3, Akr1c3, Csf1, Jag2, Plcg1, Rpl37a, Sod2, Topors, Hras, Mdm2, Camk2g, Fstl1, Il13ra1, Mtap and Tp53 were associated with multiple survival events.
Most genes (from 90 to 96%) were associated with survival in a general or cohort-independent manner and thus the same trend is observed across all clinical levels studied. The most extreme associations between profiles and survival were observed for Syne1, Pdcd4, Ighg1, Tgfa, Pla2g7, and Paics. Several genes were found to have a cohort-dependent association with survival and these associations are the basis for individualized prognostic and gene-based therapies. C2, Egfr, Prkcb, Igf2bp3, and Gdf10 had gender-dependent associations; Sox10, Rps20, Rab31, and Vav3 had race-dependent associations; Chi3l1, Prkcb, Polr2d, and Apool had therapy-dependent associations. Biological processes associated glioblastoma survival included morphogenesis, cell cycle, aging, response to stimuli, and programmed cell death.

Conclusions
Known biomarkers of glioblastoma survival were confirmed, and new general and clinical-dependent gene profiles were uncovered. The comparison of biomarkers across glioblastoma phases and functional analyses offered insights into the role of genes. These findings support the development of more accurate and personalized prognostic tools and gene-based therapies that improve the survival and quality of life of individuals afflicted by glioblastoma multiforme.
Molecular identification of Clonorchis sinensis and discrimination with other opisthorchid liver fluke species using multiple Ligation-depended Probe Amplification (MLPA)
Authors: Sun Jiufeng , Xu Jin , Liang Pei , Mao Qiang , Huang Yan , Lv Xiaoli , Deng Chuanhuan , Liang Chi , de Hoog G S , Yu Xinbing 
Published: June 2011

Abstract

Background
Infections with the opisthorchid liver flukes Clonorchis sinensis, Opisthorchis viverrini, and O. felineus cause severe health problems globally, particularly in Southeast Asia. Early identification of the infection is essential to provide timely and appropriate chemotherapy to patients.

Results
In this study we evaluate a PCR-based molecular identification method, Multiplex Ligation-dependent Probe Amplification (MLPA), which allows rapid and specific detection of single nucleotide acid differences between Clonorchis sinensis, Opisthorchis viverrini and O. felineus. Three probe pairs were derived from the Internally Transcribed Spacer 1 (ITS1) of three opisthorchid liver flukes using a systematic phylogenetic analysis. Specific loci were detected in all three species, yielding three amplicons with 198,172 and 152 bp, respectively, while no cross reactions were observed. A panel of 66 C. sinensis isolates was screened using MLPA. All species were positively identified, and no inhibition was observed. The detection limit was 103 copies of the ITS gene for the three liver flukes, or about 60 pg genomic DNA for Clonorchis sinensis. Amplification products can be detected by electrophoresis on agarose gel or in a capillary sequencer. In addition, genomic DNA of Clonorchis sinensis in fecal samples of infected rats was positively amplified by MLPA.

Conclusion
The flexibility and specificity make MLPA a potential tool for specific identification of infections by opisthorchid liver flukes in endemic areas.
Gene expression in bryozoan larvae suggest a fundamental importance of pre-patterned blastemic cells in the bryozoan life-cycle
Authors: Fuchs Judith , Martindale Mark Q , Hejnol Andreas 
Published: June 2011

AbstractBackgroundBryozoa is a clade of aquatic protostomes. The bryozoan life cycle typically comprises a larval stage, which metamorphoses into a sessile adult that proliferates by asexual budding to form colonies. The homology of bryozoan larvae with other protostome larvae is enigmatic. Bryozoan larvae exhibit blastemic tissues that contribute to build the adult during morphogenesis. However, it remains unclear if the cells of these tissues are pre-determined according to their future fate or if the cells are undifferentiated, pluripotent stem cells. Gene expression studies can help to identify molecular patterning of larval and adult tissues and enlighten the evolution of bryozoan life cycle stages.ResultsWe investigated the spatial expression of 13 developmental genes in the larval stage of the gymnolaemate bryozoanBugula neritina. We found most genes expressed in discrete regions in larval blastemic tissues that form definitive components of the adult body plan. Only two of the 13 genes,BnTropomyosinandBnFoxAB, were exclusively expressed in larval tissues that are discarded during metamorphosis.ConclusionsOur results suggest that the larval blastemas inBugulaare pre-patterned according to their future fate in the adult. The gene expression patterns indicate that some of the bryozoan blastemas can be interpreted to correspond to homologous adult tissues of other animals. This study challenges an earlier proposed view that metazoan larvae share homologous undifferentiated "set-aside cells", and instead points to an independent origin of the bryozoan larval stage with respect to other lophotrochozoans.
Imaging the effect of receptor for advanced glycation endproducts on angiogenic response to hindlimb ischemia in diabetes
Authors: Tekabe Yared , Shen Xiaoping , Luma Joane , Weisenberger Drew , Yan Shi Fang , Haubner Roland , Schmidt Ann Marie , Johnson Lynne 
Published: June 2011

Abstract

Background
Receptor for advanced glycation endproducts (RAGE) expression contributes to the impaired angiogenic response to limb ischemia in diabetes. The aim of this study was to detect the effect of increased expression of RAGE on the angiogenic response to limb ischemia in diabetes by targeting αvβ3 integrin with 99mTc-labeled Arg-Gly-Asp (RGD).

Methods
Male wild-type (WT) C57BL/6 mice were either made diabetic or left as control for 2 months when they underwent femoral artery ligation. Four groups were studied at days 3 to 7 after ligation: WT without diabetes (NDM) (n = 14), WT with diabetes (DM) (n = 14), RAGE-/- NDM (n = 16), and RAGE-/- DM (n = 14). Mice were injected with 99mTc-HYNIC-RGD and imaged. Count ratios for ischemic/non-ischemic limbs were measured. Muscle was stained for RAGE, αvβ3, and lectins.

Results
There was no difference in count ratio between RAGE-/- and WT NDM groups. Mean count ratio was lower for WT DM (1.38 ± 0.26) vs. WT NDM (1.91 ± 0.34) (P<0.001). Mean count ratio was lower for the RAGE-/- DM group than for RAGE-/- NDM group (1.75 ± 0.22 vs. 2.02 ± 0.29) (P<0.001) and higher than for the WT DM group (P<0.001). Immunohistopathology supported the scan findings.

Conclusions

In vivo imaging of αvβ3 integrin can detect the effect of RAGE on the angiogenic response to limb ischemia in diabetes.
Telomerase expression and telomere length in breast cancer and their associations with adjuvant treatment and disease outcome
Authors: Lu Lingeng , Zhang Chong , Zhu Gongjian , Irwin Melinda , Risch Harvey , Menato Guido , Mitidieri Marco , Katsaros Dionyssios , Yu Herbert 
Published: June 2011

Abstract
Introduction
Telomere length plays important roles in maintaining genome stability and regulating cell replication and death. Telomerase has functions not only to extend telomere length but also to repair DNA damage. Studies have shown that telomerase may increase cancer cell resistance to DNA-damaging anticancer agents; tamoxifen may suppress telomerase expression in breast cancer cells. This study aimed to investigate the role of telomere length and telomerase activity in breast cancer prognosis.

Methods
qPCR and qRT-PCR were used to analyze telomere length and telomerase expression, respectively, in tumor samples of 348 breast cancer patients. Cox regression analysis was performed to examine telomere length and telomerase expression in association with disease-free survival and cause-specific mortality.

Results
Telomere length had no relation to tumor features or disease outcomes. Telomerase expression was detected in 53% of tumors. Larger tumors or aggressive disease were more likely to have telomerase expression. Among patients treated with chemotherapy, high telomerase was found to be associated with increased risk of death (hazard ratio (HR) = 3.15; 95% CI: 1.34 to 7.40) and disease recurrence (HR = 2.04; 95% CI: 0.96 to 4.30) regardless of patient age, disease stage, tumor grade, histological type or hormone receptor status. Patients treated with endocrine therapy had different results regarding telomerase: high telomerase appeared to be associated with better survival outcomes. Telomerase expression made no survival difference in patients who received both chemotherapy and endocrine therapy.

Conclusions
Overall, telomerase expression was not associated with disease outcome, but this finding may be masked by adjuvant treatment. Patients with high telomerase expression responded poorly to chemotherapy in terms of disease-free and overall survival, but fared better if treated with endocrine therapy.
Meningitis in adult patients with a negative direct cerebrospinal fluid examination: value of cytochemical markers for differential diagnosis
Authors: Viallon Alain , Desseigne Nicolas , Marjollet Olivier , Birynczyk Albert , Belin Mathieu , Guyomarch Stephane , Borg Jacques , Pozetto Bruno , Bertrand Jean Claude , Zeni Fabrice 
Published: June 2011

Abstract
Introduction
The objective of this study was to determine the ability of various parameters commonly used for the diagnosis of acute meningitis to differentiate between bacterial and viral meningitis, in adult patients with a negative direct cerebrospinal fluid (CSF) examination.

Methods
This was a prospective study, started in 1997, including all patients admitted to the emergency unit with acute meningitis and a negative direct CSF examination. Serum and CSF samples were taken immediately on admission. The patients were divided into two groups according to the type of meningitis: bacterial (BM; group I) or viral (VM; group II). The CSF parameters investigated were cytology, protein, glucose, and lactate; the serum parameters evaluated were C-reactive protein and procalcitonin. CSF/serum glucose and lactate ratios were also assessed.

Results
Of the 254 patients with meningitis with a negative direct CSF examination, 35 had BM and 181, VM. The most highly discriminative parameters for the differential diagnosis of BM proved to be CSF lactate, with a sensitivity of 94%, a specificity of 92%, a negative predictive value of 99%, a positive predictive value of 82% at a diagnostic cut-off level of 3.8 mmol/L (area under the curve (AUC), 0.96; 95% confidence interval (CI), 0.95 to 1), and serum procalcitonin, with a sensitivity of 95%, a specificity of 100%, a negative predictive value of 100%, and a positive predictive value of 97% at a diagnostic cut-off level of 0.28 ng/ml (AUC, 0.99; 95% CI, 0.99 to 1).

Conclusions
Serum procalcitonin and CSF lactate concentrations appear to be the most highly discriminative parameters for the differential diagnosis of BM and VM.
New Perspectives on Customer “Death” Using a Generalization of the Pareto/NBD Model
Authors: Jerath Kinshuk , Fader Peter S. , Hardie Bruce G. S. 
Published: June 2011

Several researchers have proposed models of buyer behavior in noncontractual settings that assume that customers are “alive” for some period of time and then become permanently inactive. The best-known such model is the Pareto/NBD, which assumes that customer attrition (dropout or “death”) can occur at any point in calendar time. A recent alternative model, the BG/NBD, assumes that customer attrition follows a Bernoulli “coin-flipping” process that occurs in “transaction time” (i.e., after every purchase occasion). Although the modification results in a model that is much easier to implement, it means that heavy buyers have more opportunities to “die.” In this paper, we develop a model with a discrete-time dropout process tied to calendar time. Specifically, we assume that every customer periodically “flips a coin” to determine whether she “drops out” or continues as a customer. For the component of purchasing while alive, we maintain the assumptions of the Pareto/NBD and BG/NBD models. This periodic death opportunity (PDO) model allows us to take a closer look at how assumptions about customer death influence model fit and various metrics typically used by managers to characterize a cohort of customers. When the time period after which each customer makes her dropout decision (which we call period length) is very small, we show analytically that the PDO model reduces to the Pareto/NBD. When the period length is longer than the calibration period, the dropout process is “shut off,” and the PDO model collapses to the negative binomial distribution (NBD) model. By systematically varying the period length between these limits, we can explore the full spectrum of models between the “continuous-time-death” Pareto/NBD and the naïve “no-death” NBD. In covering this spectrum, the PDO model performs at least as well as either of these models; our empirical analysis demonstrates the superior performance of the PDO model on two data sets. We also show that the different models provide significantly different estimates of both purchasing-related and death-related metrics for both data sets, and these differences can be quite dramatic for the death-related metrics. As more researchers and managers make managerial judgments that directly relate to the death process, we assert that the model employed to generate these metrics should be chosen carefully.
Liver iron overload is associated with elevated SHBG concentration and moderate hypogonadotrophic hypogonadism in dysmetabolic men without genetic haemochromatosis
Authors: Gautier Alain , Lainé Fabrice , Massart Catherine , Sandret Laure , Piguel Xavier , Brissot Pierre , Balkau Beverley , Deugnier Yves , Bonnet Fabrice 
Published: June 2011

AimsTo assess the relation between moderate iron overload on sex hormone binding globulin (SHBG) levels and gonadotroph function in men with dysmetabolic iron overload syndrome and the effects of phlebotomy.MethodsThe relationship between magnetic resonance imaging assessed liver iron concentration (LIC) and plasma ferritin levels with total testosterone, bioavailable testosterone (BT), SHBG and LH levels, were studied in 50 men with moderate dysmetabolic iron excess, in the absence of genetic haemochromatosis, who were randomised to phlebotomy therapy or to normal care.ResultsFour patients (8%) had low total testosterone (<10.4 nmol/l) and 13 patients (26%) had low BT (<2.5 nmol/l). In the entire population, those with LIC above the median (90 μmol/l) had a higher mean SHBG (P=0.028), lower LH (P=0.039) than those with LIC below the median. In multivariable analysis (adjusted for age, and fasting insulin) LIC was significantly associated with SHBG (positively) and LH (negatively). Patients in the highest quartile of SHBG had higher LIC (P=0.010) and higher ferritinaemia (P=0.012) than those in the three other quartiles. Iron depletion by venesection did not significantly improve any hormonal levels.ConclusionsHypogonadism is not infrequent in men with dysmetabolic iron overload syndrome. Liver iron excess is associated with increased plasma SHBG and moderate hypogonadotrophic hypogonadism. Phlebotomy therapy needs further investigation in symptomatic hypogonadal men with dysmetabolic iron excess.
Assessment of primary cancers in GH-treated adult hypopituitary patients: an analysis from the Hypopituitary Control and Complications Study
Authors: Child Christopher J , Zimmermann Alan G , Woodmansee Whitney W , Green Daniel M , Li Jian J , Jung Heike , Erfurth Eva Marie , Robison Leslie L 
Published: June 2011

ObjectiveGH and IGFs have mitogenic properties, causing speculation that GH treatment could increase risk of malignancy. While studies in GH-treated childhood cancer survivors have suggested a slight increase in second neoplasms, studies in GH-treated adults have been equivocal.DesignIncidence of de novo and second cancers was evaluated in 6840 GH-treated and 940 non GH-treated adult patients in the Hypopituitary Control and Complications Study pharmacoepidemiological database.MethodsEvident cancer cases were evaluated in the main analysis, with sensitivity analyses including probable and possible cancers. Standardized incidence ratios (SIRs) for cancers were calculated using Surveillance, Epidemiology and End Results for the USA and GLOBOCAN for all other countries.ResultsDuring the mean follow-up of 3.7 years/GH-treated patient, 142 evident cancer cases were identified, giving an overall SIR of 0.88 (95% confidence interval (CI) 0.74–1.04); 95% CIs included the value of 1.0 for each country examined. The SIR for GH-treated patients from the USA (71 cases) was 0.94 (95% CI 0.73–1.18), and for non GH-treated patients from the USA (27 cases) was 1.16 (95% CI 0.76–1.69). For GH-treated patients from the USA aged <35 years, the SIR (six cases) was 3.79 (1.39–8.26), with SIR not elevated for all other age categories; SIR for patients from the USA with childhood onset (CO) GH deficiency (GHD) was 2.74 (95% CI 1.18–5.41). The SIR for colorectal cancer in GH-treated patients (11 cases) was 0.60 (95% CI 0.30–1.08).ConclusionsWith relatively short follow-up, the overall primary cancer risk in 6840 patients receiving GH as adults was not increased. Elevated SIRs were found for subgroups in the USA cohort defined by age <35 years or CO GHD.
Unacylated ghrelin is associated with changes in body composition and body fat distribution during long-term exercise intervention
Authors: Cederberg Henna , Rajala Ulla , Koivisto Vesa-Matti , Jokelainen Jari , Surcel Heljä-Marja , Keinänen-Kiukaanniemi Sirkka , Laakso Markku 
Published: June 2011

ObjectiveGhrelin, a gut–brain peptide involved in energy homeostasis, circulates predominantly (>90%) in unacylated form. Previous studies, however, have focused on total and acylated ghrelin, and the role of unacylated ghrelin (UAG) is not well understood. Particularly, the association of UAG with weight loss and changes in body composition in adults remains unclear. We hypothesized that exercise-associated increase in UAG level is associated with weight loss, favorable changes in body composition, and body fat distribution.Design and methodsA prospective study of 552 young men (mean age 19.3 and range 19–28 years) undergoing military service with structured 6-month exercise training program. Exercise performance, body composition, and biochemical measurements were obtained at baseline and follow-up. Association between changes in UAG levels and body composition and body fat distribution were evaluated.ResultsAn increase in UAG level during the exercise intervention was associated with reduced weight, fat mass (FM), fat percentage (fat %), and waist circumference, but not with fat-free mass. Inverse associations of changes in UAG level with changes in waist circumference and fat % were independent of weight at baseline, and changes in weight and exercise performance. Associations of changes in UAG level with waist circumference were significantly stronger than with fat % after the adjustment for confounding variables.ConclusionUAG is associated with changes in body weight and body composition during an intensive long-term exercise intervention in young men. The association of UAG levels with changes in central obesity was stronger than with total FM.