bluuebunny/crossref_metadata_2025_split huggingface dataset:
Accuracy of RNA-Seq and its dependence on sequencing depth
Authors: Cai Guoshuai , Li Hua , Lu Yue , Huang Xuelin , Lee Juhee , Müller Peter , Ji Yuan , Liang Shoudan 
Published: August 2012

AbstractBackgroundThe cost of DNA sequencing has undergone a dramatical reduction in the past decade. As a result, sequencing technologies have been increasingly applied to genomic research. RNA-Seq is becoming a common technique for surveying gene expression based on DNA sequencing. As it is not clear how increased sequencing capacity has affected measurement accuracy of mRNA, we sought to investigate that relationship.ResultWe empirically evaluate the accuracy of repeated gene expression measurements using RNA-Seq. We identify library preparation steps prior to DNA sequencing as the main source of error in this process. Studying three datasets, we show that the accuracy indeed improves with the sequencing depth. However, the rate of improvement as a function of sequence reads is generally slower than predicted by the binomial distribution. We therefore used the beta-binomial distribution to model the overdispersion. The overdispersion parameters we introduced depend explicitly on the number of reads so that the resulting statistical uncertainty is consistent with the empirical data that measurement accuracy increases with the sequencing depth. The overdispersion parameters were determined by maximizing the likelihood. We shown that our modified beta-binomial model had lower false discovery rate than the binomial or the pure beta-binomial models.ConclusionWe proposed a novel form of overdispersion guaranteeing that the accuracy improves with sequencing depth. We demonstrated that the new form provides a better fit to the data.
Expression of cassini, a murine gamma-satellite sequence conserved in evolution, is regulated in normal and malignant hematopoietic cells
Authors: Arutyunyan Anna , Stoddart Sonia , Yi Sun-ju , Fei Fei , Lim Min , Groffen Paula , Feldhahn Niklas , Groffen John , Heisterkamp Nora 
Published: August 2012

Abstract

Background
Acute lymphoblastic leukemia (ALL) cells treated with drugs can become drug-tolerant if co-cultured with protective stromal mouse embryonic fibroblasts (MEFs).

Results
We performed transcriptional profiling on these stromal fibroblasts to investigate if they were affected by the presence of drug-treated ALL cells. These mitotically inactivated MEFs showed few changes in gene expression, but a family of sequences of which transcription is significantly increased was identified. A sequence related to this family, which we named cassini, was selected for further characterization. We found that cassini was highly upregulated in drug-treated ALL cells. Analysis of RNAs from different normal mouse tissues showed that cassini expression is highest in spleen and thymus, and can be further enhanced in these organs by exposure of mice to bacterial endotoxin. Heat shock, but not other types of stress, significantly induced the transcription of this locus in ALL cells. Transient overexpression of cassini in human 293 embryonic kidney cells did not increase the cytotoxic or cytostatic effects of chemotherapeutic drugs but provided some protection. Database searches revealed that sequences highly homologous to cassini are present in rodents, apicomplexans, flatworms and primates, indicating that they are conserved in evolution. Moreover, CASSINI RNA was induced in human ALL cells treated with vincristine. Surprisingly, cassini belongs to the previously reported murine family of γ-satellite/major satellite DNA sequences, which were not known to be present in other species.

Conclusions
Our results show that the transcription of at least one member of these sequences is regulated, suggesting that this has a function in normal and transformed immune cells. Expression of these sequences may protect cells when they are exposed to specific stress stimuli.
A nationwide study on reproductive function, ovarian reserve, and risk of premature menopause in female survivors of childhood cancer: design and methodological challenges
Authors: Overbeek Annelies , van den Berg Marleen H , Kremer Leontien CM , van den Heuvel-Eibrink Marry M , Tissing Wim JE , Loonen Jacqueline J , Versluys Birgitta , Bresters Dorine , Kaspers Gertjan JL , Lambalk Cornelis B , van Leeuwen Flora E , van Dulmen-den Broeder Eline 
Published: August 2012

Abstract

Background
Advances in childhood cancer treatment over the past decades have significantly improved survival, resulting in a rapidly growing group of survivors. However, both chemo- and radiotherapy may adversely affect reproductive function. This paper describes the design and encountered methodological challenges of a nationwide study in the Netherlands investigating the effects of treatment on reproductive function, ovarian reserve, premature menopause and pregnancy outcomes in female childhood cancer survivors (CCS), the DCOG LATER-VEVO study.

Methods
The study is a retrospective cohort study consisting of two parts: a questionnaire assessing medical, menstrual, and obstetric history, and a clinical assessment evaluating ovarian and uterine function by hormonal analyses and transvaginal ultrasound measurements. The eligible study population consists of adult female 5-year survivors of childhood cancer treated in the Netherlands, whereas the control group consists of age-matched sisters of the participating CCS. To date, study invitations have been sent to 1611 CCS and 429 sister controls, of which 1215 (75%) and 333 (78%) have responded so far. Of these responders, the majority consented to participate in both parts of the study (53% vs. 65% for CCS and sister controls respectively). Several challenges were encountered involving the study population: dealing with bias due to the differences in characteristics of several types of (non-) participants and finding an adequately sized and well-matched control group. Moreover, the challenges related to the data collection process included: differences in response rates between web-based and paper-based questionnaires, validity of self-reported outcomes, interpretation of clinical measurements of women using hormonal contraceptives, and inter- and intra-observer variation of the ultrasound measurements.

Discussion
The DCOG LATER-VEVO study will provide valuable information about the reproductive potential of paediatric cancer patients as well as long-term survivors of childhood cancer. Other investigators planning to conduct large cohort studies on late effects may encounter similar challenges as those encountered during this study. The solutions to these challenges described in this paper may be useful to these investigators.

Trial registration
NTR2922; http://www.trialregister.nl/trialreg/admin/rctview.asp?TC=2922
Reovirus exerts potent oncolytic effects in head and neck cancer cell lines that are independent of signalling in the EGFR pathway
Authors: Twigger Katie , Roulstone Victoria , Kyula Joan , Karapanagiotou Eleni M , Syrigos Konstantinos N , Morgan Richard , White Christine , Bhide Shreerang , Nuovo Gerard , Coffey Matt , Thompson Brad , Jebar Adel , Errington Fiona , Melcher Alan A , Vile Richard G , Pandha Hardev S , Harrington Kevin J 
Published: August 2012

Abstract

Background
Reovirus exploits aberrant signalling downstream of Ras to mediate tumor-specific oncolysis. Since ~90% squamous cell carcinomas of the head and neck (SCCHN) over-express EGFR and SCCHN cell lines are sensitive to oncolytic reovirus, we conducted a detailed analysis of the effects of reovirus in 15 head and neck cancer cell lines. Both pre- and post-entry events were studied in an attempt to define biomarkers predictive of sensitivity/resistance to reovirus. In particular, we analysed the role of EGFR/Ras signalling in determining virus-mediated cytotoxicity in SCCHN.

Methods
To test whether EGFR pathway activity was predictive of increased sensitivity to reovirus, correlative analyses between reoviral IC50 by MTT assay and EGFR levels by western blot and FACS were conducted. Inhibition or stimulation of EGFR signalling were analysed for their effect on reoviral oncolysis by MTT assay, and viral growth by TCID50 assay. We next analysed the effects of inhibiting signalling downstream of Ras, by specific inhibitors of p38MAPK, PI3-K or MEK, on reoviral killing examined by MTT assay. The role of PKR in reoviral killing was also determined by blockade of PKR using 2-aminopurine and assaying for cell survival by MTT assay. The apoptotic response of SCCHN to reovirus was examined by western blot analysis of caspase 3 cleavage.

Results
Correlative analyses between reoviral sensitivity and EGFR levels revealed no association. Intermediate sub-viral and core particles showed the same infectivity/cytotoxicity as intact reovirus. Therefore, sensitivity was not determined by cell entry. In 4 cell lines, oncolysis and viral growth were both unaffected by inhibition or stimulation of EGFR signalling. Inhibition of signalling downstream of Ras did not abrogate reoviral oncolysis and, in addition, modulation of PKR using 2-aminopurine did not alter reovirus sensitivity in resistant cell lines. Caspase 3 cleavage was not detected in infected cells and oncolysis was observed in pan-caspase inhibited cells.

Conclusions
In summary, reovirus is potently oncolytic in a broad panel of SCCHN cell lines. Attempts to define sensitivity/resistance by analysis of the EGFR/Ras/MAPK pathway have failed to provide a clear predictive biomarker of response. Further analysis of material from in vitro and clinical studies is ongoing in an attempt to shed further light on this issue.
Fecal calprotectin levels are higher in rural than in urban Chinese infants and negatively associated with growth
Authors: Liu Jin-Rong , Sheng Xiao-Yang , Hu Yan-Qi , Yu Xiao-Gang , Westcott Jamie E , Miller Leland V , Krebs Nancy F , Hambidge K Michael 
Published: August 2012

Abstract

Background
Fecal calprotectin (FC) is an established simple biomarker of gut inflammation. To examine a possible relationship between linear growth and gut inflammation, we compared fecal calprotectin levels in 6 month old infants from poor rural vs affluent urban families.

Methods
The project was a cross-sectional comparison of FC from rural and urban populations in China. The relationship between length-for-age Z-score (LAZ) and FC concentrations were also compared. Single fecal samples were assayed for FC using EK-CAL ELISA kits.

Results
The age of subjects for both locations was 6.1 ± 0.2 mo; all were apparently healthy. The mean ± SD of the LAZ for the rural and urban infants were −0.6 ± 0.9 and 0.4 ± 0.9, respectively. FC had a non-normal distribution. The median FC of 420.9 and 140.1 μg/g for rural and urban infants, respectively, were significantly different (P < 0.0001). For the rural group, linear regression analysis showed that an increase in FC of 100 μg/g was associated with a decrease of 0.06 in LAZ.

Conclusion
FC levels were significantly elevated in the rural infants and high concentrations accounted for approximately one-third of the low LAZ scores of these infants.
Prenatal polychlorinated biphenyl exposure is associated with decreased gestational length but not birth weight: archived samples from the Child Health and Development Studies pregnancy cohort
Authors: Kezios Katrina L , Liu Xinhua , Cirillio Piera M , Kalantzi Olga I , Wang Yunzhu , Petreas Myrto X , Park June-Soo , Bradwin Gary , Cohn Barbara A , Factor-Litvak Pam 
Published: August 2012

Abstract

Background
Polychlorinated biphenyls (PCBs), known endocrine disruptors, were banned in 1979 but persist in the environment. Previous studies are inconsistent regarding prenatal exposure to PCBs and pregnancy outcomes. We investigated associations between prenatal exposure to PCBs and gestational length and birth weight.

Methods
In a sample of 600 infants (born between 1960 and 1963) randomly selected from Child Health and Development Studies participants followed through adolescence we measured 11 PCB congeners in maternal post partum sera (within three days of delivery). Length of gestation was computed from the reported first day of the last menstrual period (LMP) and delivery date. Linear regression was used to estimate associations between PCB exposure and gestational age and birth weight, adjusting for potential confounders. PCBs were grouped according to hypothesized biological action (1b (sum of weak phenobarbital inducers), 2b (sum of limited dioxin activity), and 3 (sum of CYP1A and CYP2b inducers)) or degree of ortho- substitution (mono, di, tri). Secondary analyses examined associations between total PCB exposure and exposure to individual congeners.

Results
Each unit increase in mono-ortho substituted PCBs was associated with a 0.30 week decrease (95% confidence interval (CI) -0.59, -0.016), corresponding to a 2.1 (95% CI −4.13, -0.11) day decrease in length of gestation. Similar associations were estimated for di-ortho substituted PCBs, (1.4 day decrease; (95% CI −2.9, 0.1)) and group 3 PCBs (0.84 day decrease; (95% CI −1.8, 0.11). We found similar associations in congener specific analyses and for the sum of congeners.

Conclusions
Our study provides new evidence that PCB exposure shortens length of gestation in humans. This may have public health implications for population exposures.
Non-occupational exposure to paint fumes during pregnancy and risk of congenital anomalies: a cohort study
Authors: Hjortebjerg Dorrit , Andersen Anne-Marie Nybo , Garne Ester , Raaschou-Nielsen Ole , Sørensen Mette 
Published: August 2012

AbstractBackgroundOccupational exposure to organic solvents during the 1sttrimester of pregnancy has been associated with congenital anomalies. Organic solvents are also used in the home environments in paint products, but no study has investigated the effect of such exposure in a general population.MethodsWe studied associations between residential exposure to paint fumes during the 1sttrimester of pregnancy and predefined subgroups of congenital anomalies, using data from the Danish National Birth Cohort (DNBC). During 2001 and 2003, a total of 20 103 pregnant women, enrolled in the DNBC, were interviewed in the 30thweek of gestation about the use of paint in their residence during pregnancy. By the end of first trimester, information about smoking habits, alcohol consumption and occupation were collected. Information on congenital anomalies was obtained from national registers. Associations were examined by estimating odds ratios (OR) using logistic regression.ResultsIn total 1404 women (7%) had been exposed to paint fumes during the 1sttrimester of pregnancy and 1086 children were diagnosed with congenital anomalies; 73 children with congenital anomalies had been exposed to paint fumes in utero. Exposure to paint fumes seemed positively associated with congenital anomalies of the nervous system (OR 2.19, 95% confidence interval (CI) 0.76 to 6.32), ear, face and neck (OR 2.15, 95% CI 0.84 to 5.55) and the renal system (OR 2.16, 95% CI 1.02 to 4.58) after adjustment for maternal age, smoking, alcohol consumption and occupational solvent exposure. Congenital anomalies in the remaining subgroups were not associated with the exposure.ConclusionsOur results suggest that in the general population, exposure to paint fumes during the 1sttrimester of pregnancy may increase the risk of some types of congenital anomalies, but the findings need to be confirmed.
The bidirectional interation between pancreatic cancer and diabetes
Authors: Li Junhui , Cao Gang , Ma Qingyong , Liu Han , Li Wei , Han Liang 
Published: August 2012

Abstract
The bidirectional interation between pancreatic cancer (PanCa) and diabetes has been confirmed by epidemiological studies, which provide evidence-based medical support for further research into the mechanisms involved in the interaction. We reviewed the literature regarding the role of diabetes in the generation and progression of PanCa and the mechanism by which PanCa induces diabetes for its malignant progression. The effect of antidiabetic drugs on the occurrence and prognosis of PanCa was also reviewed. Diabetes may directly promote the progression of PanCa by pancreatic duct enlargement and hypertension, as well as by enabling an increased tumor volume. Hyperinsulinemia, insulin resistance, cytokines, hyperglycemia and genotype change are also important factors in the progression of PanCa with diabetes. Hyperglycemia may be the first clinical manifestation and is helpful in the early diagnosis of PanCa. Furthermore, antidiabetic drugs can have different effects on the occurrence and prognosis of PanCa. The bidirectional interation between PanCa and diabetes is involved in the occurrence, proliferation, invasion, metastasis and prognosis of PanCa with diabetes. The discovery of biomarkers for the early diagnosis of PanCa, as well as the novel usage of metformin for its antitumor effects and determining the potential mechanisms of these effects, may be the next direction for PanCa research and treatment.
Chloroplasts-mediated biosynthesis of nanoscale Au-Ag alloy for 2-butanone assay based on electrochemical sensor
Authors: Zhang Yixia , Gao Guo , Qian Qirong , Cui Daxiang 
Published: August 2012

Abstract
We reported a one-pot, environmentally friendly method for biosynthesizing nanoscale Au-Ag alloy using chloroplasts as reducers and stabilizers. The prepared nanoscale Au-Ag alloy was characterized by UV–visible spectroscopy, X-ray diffraction (XRD) and high resolution transmission electron microscopy (HR-TEM). Fourier transform infrared spectroscopy (FTIR) analysis was further used to identify the possible biomolecules from chloroplasts that are responsible for the formation and stabilization of Au-Ag alloy. The FTIR results showed that chloroplast proteins bound to the nanoscale Au-Ag alloy through free amino groups. The bimetallic Au-Ag nanoparticles have only one plasmon band, indicating the formation of an alloy structure. HR-TEM images showed that the prepared Au-Ag alloy was spherical and 15 to 20 nm in diameter. The high crystallinity of the Au-Ag alloy was confirmed by SAED and XRD patterns. The prepared Au-Ag alloy was dispersed into multiwalled carbon nanotubes (MWNTs) to form a nanosensing film. The nanosensing film exhibited high electrocatalytic activity for 2-butanone oxidation at room temperature. The anodic peak current (Ip) has a linear relationship with the concentrations of 2-butanone over the range of 0.01% to 0.075% (v/v), when analyzed by cyclic voltammetry. The excellent electronic catalytic characteristics might be attributed to the synergistic electron transfer effects of Au-Ag alloy and MWNTs. It can reasonably be expected that this electrochemical biosensor provided a promising platform for developing a breath sensor to screen and pre-warn of early cancer, especially gastric cancer.
Tripled fixed point of W-compatible mappings in abstract metric spaces
Authors: Aydi Hassen , Abbas Mujahid , Sintunavarat Wutiphol , Kumam Poom 
Published: August 2012

AbstractIn this paper, we introduce the concepts ofW-compatible mappings for mappingsF:X×X×X→Xandg:X→X, where(X,d)is an abstract metric space. We establish tripled coincidence and common tripled fixed point theorems in such spaces. The presented theorems generalize and extend several well-known comparable results in literature, in particular the results of Abbas, Ali and Radenović (Appl. Math. Comput. 217:195-202, 2010). We also provide an example to illustrate our obtained results.MSC:54H25, 47H10.
Experimental chronic hepatitis B infection of neonatal tree shrews (Tupaia belangeri chinensis): A model to study molecular causes for susceptibility and disease progression to chronic hepatitis in humans
Authors: Wang Qi , Schwarzenberger Paul , Yang Fang , Zhang Jingjing , Su Jianjia , Yang Chun , Cao Ji , Ou Chao , Liang Liang , Shi Junlin , Yang Fang , Wang Duoping , Wang Jia , Wang Xiaojuan , Ruan Ping , Li Yuan 
Published: August 2012

Abstract

Background
Hepatitis B virus (HBV) infection continues to be an escalating global health problem. Feasible and effective animal models for HBV infection are the prerequisite for developing novel therapies for this disease. The tree shrew (Tupaia) is a small animal species evolutionary closely related to humans, and thus is permissive to certain human viral pathogens. Whether tree shrews could be chronically infected with HBV in vivo has been controversial for decades. Most published research has been reported on adult tree shrews, and only small numbers of HBV infected newborn tree shrews had been observed over short time periods. We investigated susceptibility of newborn tree shrews to experimental HBV infection as well as viral clearance over a protracted time period.

Results
Forty-six newborn tree shrews were inoculated with the sera from HBV-infected patients or tree shrews. Serum and liver samples of the inoculated animals were periodically collected and analyzed using fluorescence quantitative polymerase chain reaction, enzyme-linked immunosorbent assay, Southern blot, and immunohistochemistry. Six tree shrews were confirmed and four were suspected as chronically HBV-infected for more than 48 (up to 228) weeks after inoculation, including three that had been inoculated with serum from a confirmed HBV-infected tree shrew.

Conclusions
Outbred neonatal tree shrews can be long-term chronically infected with HBV at a frequency comparable to humans. The model resembles human disease where also a smaller proportion of infected individuals develop chronic HBV related disease. This model might enable genetic and immunologic investigations which would allow determination of underlying molecular causes favoring susceptibility for chronic HBV infection and disease establishment vs. viral clearance.
Simultaneous RNA quantification of human and retroviral genomes reveals intact interferon signaling in HTLV-1-infected CD4+ T cell lines
Authors: Moens Britta , Pannecouque Christophe , López Giovanni , Talledo Michael , Gotuzzo Eduardo , Khouri Ricardo , Bittencourt Achiléa , Farré Lourdes , Galvão-Castro Bernardo , Vandamme Anne-Mieke , Van Weyenbergh Johan 
Published: August 2012

AbstractBackgroundIFN-α contributes extensively to host immune response upon viral infection through antiviral, pro-apoptotic, antiproliferative and immunomodulatory activities. Although extensively documented in various types of human cancers and viral infections, controversy exists in the exact mechanism of action of IFN-α in human immunodeficiency virus type 1 (HIV-1) and human T-lymphotropic virus type 1 (HTLV-1) retroviral infections.ResultsIFN-α displayed strong anti-HIV-1 effects in HIV-1/HTLV-1 co-infected MT-4 cells in vitro, demonstrated by the dose-dependent inhibition of the HIV-1-induced cytopathic effect (IC50 = 83.5 IU/ml, p < 0.0001) and p24 levels in cell-free supernatant (IC50 = 1.2 IU/ml, p < 0.0001). In contrast, IFN-α treatment did not affect cell viability or HTLV-1 viral mRNA levels in HTLV-1 mono-infected cell lines, based on flow cytometry and nCounter analysis, respectively. However, we were able to confirm the previously described post-transcriptional inhibition of HTLV-1 p19 secretion by IFN-α in cell lines (p = 0.0045), and extend this finding to primary Adult T cell Leukemia patient samples (p = 0.031). In addition, through microarray and nCounter analysis, we performed the first genome-wide simultaneous quantification of complete human and retroviral transciptomes, demonstrating significant transcriptional activation of interferon-stimulated genes without concomitant decrease of HTLV-1 mRNA levels.ConclusionsTaken together, our results indicate that both the absence of in vitro antiproliferative and pro-apoptotic activity as well as the modest post-transcriptional antiviral activity of IFN-α against HTLV-1, were not due to a cell-intrinsic defect in IFN-α signalisation, but rather represents a retrovirus-specific phenomenon, considering the strong HIV-1 inhibition in co-infected cells.