bluuebunny/crossref_metadata_2025_split huggingface dataset:
Validation of oligoarrays for quantitative exploration of the transcriptome
Authors: Nygaard Vigdis , Liu Fang , Holden Marit , Kuo Winston P , Trimarchi Jeff , Ohno-Machado Lucila , Cepko Connie L , Frigessi Arnoldo , Glad Ingrid K , van de Wiel Mark A , Hovig Eivind , Lyng Heidi 
Published: May 2008

Abstract

Background
Oligoarrays have become an accessible technique for exploring the transcriptome, but it is presently unclear how absolute transcript data from this technique compare to the data achieved with tag-based quantitative techniques, such as massively parallel signature sequencing (MPSS) and serial analysis of gene expression (SAGE). By use of the TransCount method we calculated absolute transcript concentrations from spotted oligoarray intensities, enabling direct comparisons with tag counts obtained with MPSS and SAGE. The tag counts were converted to number of transcripts per cell by assuming that the sum of all transcripts in a single cell was 5·105. Our aim was to investigate whether the less resource demanding and more widespread oligoarray technique could provide data that were correlated to and had the same absolute scale as those obtained with MPSS and SAGE.

Results
A number of 1,777 unique transcripts were detected in common for the three technologies and served as the basis for our analyses. The correlations involving the oligoarray data were not weaker than, but, similar to the correlation between the MPSS and SAGE data, both when the entire concentration range was considered and at high concentrations. The data sets were more strongly correlated at high transcript concentrations than at low concentrations. On an absolute scale, the number of transcripts per cell and gene was generally higher based on oligoarrays than on MPSS and SAGE, and ranged from 1.6 to 9,705 for the 1,777 overlapping genes. The MPSS data were on same scale as the SAGE data, ranging from 0.5 to 3,180 (MPSS) and 9 to1,268 (SAGE) transcripts per cell and gene. The sum of all transcripts per cell for these genes was 3.8·105 (oligoarrays), 1.1·105 (MPSS) and 7.6·104 (SAGE), whereas the corresponding sum for all detected transcripts was 1.1·106 (oligoarrays), 2.8·105 (MPSS) and 3.8·105 (SAGE).

Conclusion
The oligoarrays and TransCount provide quantitative transcript concentrations that are correlated to MPSS and SAGE data, but, the absolute scale of the measurements differs across the technologies. The discrepancy questions whether the sum of all transcripts within a single cell might be higher than the number of 5·105 suggested in the literature and used to convert tag counts to transcripts per cell. If so, this may explain the apparent higher transcript detection efficiency of the oligoarrays, and has to be clarified before absolute transcript concentrations can be interchanged across the technologies. The ability to obtain transcript concentrations from oligoarrays opens up the possibility of efficient generation of universal transcript databases with low resource demands.
Excess of transmission of the G allele of the -1438A/G polymorphism of the 5-HT2Areceptor gene in patients with schizophrenia responsive to antipsychotics
Authors: Benmessaoud Dalila , Hamdani Nora , Boni Claudette , Ramoz Nicolas , Hamon Michel , Kacha Farid , Gorwood Philip 
Published: May 2008

AbstractBackgroundThe -1438A/G polymorphism of the 5-HT2Agene has been found to be associated with clinical response to clozapine and other second generation antipsychotics. Testing the impact of this marker on response to first generation antipsychotics (which have a lower affinity for the 5-HT2Areceptor) provides the opportunity to help disentangling the two different roles that this polymorphism might have. A psychopharmacogenetic role should be detected only for antipsychotics with high affinity to the 5-HT2Areceptor (therefore to second generation antipsychotics). An alternative role would imply tagging a subgroup of patients responsive to any antipsychotic, whatever their affinity, meaning that the association is more depending on non pharmacological charaterictics, such as clinical specificities.MethodsA family-based sample of 100 Algerian patients with schizophrenia (according to DSM-IV criteria) and their 200 biological parents was recruited, in order to avoid stratification biases. Patients were all treated, or have been treated, by conventional antipsychotics (mainly haloperidol) for at least four weeks, at appropriate dosage. May and Dencker scale was used to distinguish responders and non responders.ResultsNo allele of the -1438A/G polymorphism of the 5-HT2Agene was transmitted in excess (50 transmitted for 38 untransmitted) in the whole sample of patients with schizophrenia (p = .90). In contrast, a significant excess of transmission of the G allele was observed (p = .02) in the subgroup of patients with good treatment response (17 transmitted for 6 untransmitted).ConclusionUsing a TDT approach, we showed that the G allele of the -1438A/G polymorphism of the gene coding for the 5-HT2Areceptor was associated to schizophrenia with good response to conventional antipsychotics, although this conclusion is based on 88 informative patients only. Because previous data showed the same result with atypical antipsychotics, it can be concluded that the G allele tags a subgroup of schizophrenic patients with greater chance of improvement with antipsychotics of either type.
Highly diversified multiply drug-resistant HIV-1 quasispecies in PBMCs: a case report
Authors: Quan Yudong , Brenner Bluma G , Dascal André , Wainberg Mark A 
Published: May 2008

Abstract

Background
Although drug resistance is a major challenge in HIV therapy, the effect of drug resistance mutations on HIV evolution in vivo is not well understood. We have now investigated genetic heterogeneity in HIV-1 by performing drug resistance genotyping of the PR-RT regions of viruses derived from plasma and peripheral blood mononuclear cells (PBMCs) of a single patient who had failed multiple regimens of anti-retroviral therapy.

Results
Patterns of drug resistance mutations showed that the viral populations in PBMCs were more heterogeneous than in plasma. Extensive analysis of HIV from infected PBMCs in this patient showed that high-level diversity existed among 109 cloned PR-RT sequences and that the majority of mutations were related to drug resistance. Moreover, the PBMCs included archival species that reflected the treatment history of the patient while those in plasma were mainly related to the most recent treatment. Some of the proviral clones contained single or multiple mutations in various combinations. Approximately eighteen percent of the proviral clones derived from infected PBMCs were defective, i.e. 5.5% contained single nucleotide deletions (frameshift mutations) and 12.8% encoded in-frame stop codons (nonsense mutations). Amino acid substitutions in PR and the polymerase region of RT occurred in 12–15% of cases but were much less frequent in the RNase H region of RT, which might not have been under drug selection pressure.

Conclusion
Selective drug pressure can yield multiple drug-resistant quasispecies that include archival and replication-incompetent species in PBMC reservoirs.
Classifying transcription factor targets and discovering relevant biological features
Authors: Holloway Dustin T , Kon Mark , DeLisi Charles 
Published: May 2008

Abstract

Background
An important goal in post-genomic research is discovering the network of interactions between transcription factors (TFs) and the genes they regulate. We have previously reported the development of a supervised-learning approach to TF target identification, and used it to predict targets of 104 transcription factors in yeast. We now include a new sequence conservation measure, expand our predictions to include 59 new TFs, introduce a web-server, and implement an improved ranking method to reveal the biological features contributing to regulation. The classifiers combine 8 genomic datasets covering a broad range of measurements including sequence conservation, sequence overrepresentation, gene expression, and DNA structural properties.

Principal Findings
(1) Application of the method yields an amplification of information about yeast regulators. The ratio of total targets to previously known targets is greater than 2 for 11 TFs, with several having larger gains: Ash1(4), Ino2(2.6), Yaf1(2.4), and Yap6(2.4).
(2) Many predicted targets for TFs match well with the known biology of their regulators. As a case study we discuss the regulator Swi6, presenting evidence that it may be important in the DNA damage response, and that the previously uncharacterized gene YMR279C plays a role in DNA damage response and perhaps in cell-cycle progression.
(3) A procedure based on recursive-feature-elimination is able to uncover from the large initial data sets those features that best distinguish targets for any TF, providing clues relevant to its biology. An analysis of Swi6 suggests a possible role in lipid metabolism, and more specifically in metabolism of ceramide, a bioactive lipid currently being investigated for anti-cancer properties.
(4) An analysis of global network properties highlights the transcriptional network hubs; the factors which control the most genes and the genes which are bound by the largest set of regulators. Cell-cycle and growth related regulators dominate the former; genes involved in carbon metabolism and energy generation dominate the latter.

Conclusion
Postprocessing of regulatory-classifier results can provide high quality predictions, and feature ranking strategies can deliver insight into the regulatory functions of TFs. Predictions are available at an online web-server, including the full transcriptional network, which can be analyzed using VisAnt network analysis suite.

Reviewers
This article was reviewed by Igor Jouline, Todd Mockler(nominated by Valerian Dolja), and Sandor Pongor.
Occupational allergy due to seafood delivery: Case report
Authors: Seitz Cornelia S , Bröcker Eva B , Trautmann Axel 
Published: May 2008

Abstract

Background
Sensitization to fish or crustaceans requires intensive skin contact and/or airway exposition and therefore especially workers in the seafood processing industry may develop an occupational seafood allergy. However, even in jobs with limited direct exposure, individuals with atopic disposition not using appropriate skin protection are at risk for developing occupational seafood allergy which requires termination of employment.

Case presentation
Due to increasing workload and pressure of time a truck driver in charge of seafood deliveries for 10 years neglected preventive measures such as wearing protective cloths and gloves which resulted in increasing direct skin contact to seafood or mucosal contact to splashing storage ice. Despite his sensitization to fish and crustaceans he tried to remain in his job but with ongoing incidental allergen exposure his symptoms progressed from initial contact urticaria to generalized urticaria, anaphylaxis and finally occupational asthma.

Conclusion
Faulty knowledge and increased work load may impede time-consuming usage of preventive measures for occupational health and safety. In predisposed atopic individuals even minor allergen exposure during seafood distribution may lead to occupational seafood allergy. With ongoing allergen exposure progression to potentially life-threatening allergy symptoms may occur.
Human papillomavirus (HPV) infection and intraepithelial neoplasia and invasive cancer of the uterine cervix: a case-control study in Zaragoza, Spain
Authors: Bernal Milagros , Burillo Isabel , Mayordomo Jose I , Moros Manuel , Benito Rafael , Gil Joaquina 
Published: May 2008

Abstract

Introduction
The raw incidence of cancer of the uterine cervix is Spain is 7,8 per 100.000 inhabitants (adjusted incidence is 5.6). The incidence of this tumor is still low, but a steady increase has been seen, probably related to increasing risk factors.

Aim
To determine the frequency of infection by different types of human papillomavirus (HPV) in Papanicolau smears from women with and without cancer of the uterine cervix in Spain.

Patients and methods
A case-control study was performed in women with and without cervical cancer from Zaragoza, Spain. Pap smears from 600 cases (540 women with cervical intraepithelial neoplasms (CIN) and 60 with invasive cancer) and 1200 controls (women without those lesions) were tested by polymerase chain reaction (PCR) and typed by oligonucleotide microarray-based detection.

Results
HPV was detected in 93.3% of all samples with invasive cancer versus 17.5% of controls. OR for invasive cancer was 55 (95% CI 21.5–140,5). Statistically significant associations were also found for different grades of cervical dysplasia.

Conclusion
The strong association found between HPV infection, specifically types 16 and 18 and cancer of the uterine cervix in Zaragoza, Spain, stresses the importance of ongoing efforts to institute a vaccine program with recently approved HPV vaccines in order to prevent cervical cancer in this population.
Cartilage degradation is fully reversible in the presence of aggrecanase but not matrix metalloproteinase activity
Authors: Karsdal Morten A , Madsen Suzi H , Christiansen Claus , Henriksen Kim , Fosang Amanda J , Sondergaard Bodil C 
Published: May 2008

Abstract
Introduction
Physiological and pathophysiological cartilage turnover may coexist in articular cartilage. The distinct enzymatic processes leading to irreversible cartilage damage, compared with those needed for continuous self-repair and regeneration, remain to be identified. We investigated the capacity of repair of chondrocytes by analyzing their ability to initiate an anabolic response subsequent to three different levels of catabolic stimulation.

Methods
Cartilage degradation was induced by oncostatin M and tumour necrosis factor in articular cartilage explants for 7, 11, or 17 days. The catabolic period was followed by 2 weeks of anabolic stimulation (insulin growth factor-I). Cartilage formation was assessed by collagen type II formation (PIINP). Cartilage degradation was measured by matrix metalloproteinase (MMP) mediated type II collagen degradation (CTX-II), and MMP and aggrecanase mediated aggrecan degradation by detecting the 342FFGVG and 374ARGSV neoepitopes. Proteoglycan turnover, content, and localization were assessed by Alcian blue.

Results
Catabolic stimulation resulted in increased levels of cartilage degradation, with maximal levels of 374ARGSV (20-fold induction), CTX-II (150-fold induction), and 342FFGVG (30-fold induction) (P < 0.01). Highly distinct protease activities were found with aggrecanase-mediated aggrecan degradation at early stages, whereas MMP-mediated aggrecan and collagen degradation occurred during later stages. Anabolic treatment increased proteoglycan content at all time points (maximally, 250%; P < 0.001). By histology, we found a complete replenishment of glycosaminoglycan at early time points and pericellular localization at an intermediate time point. In contrast, only significantly increased collagen type II formation (200%; P < 0.01) was observed at early time points.

Conclusion
Cartilage degradation was completely reversible in the presence of high levels of aggrecanase-mediated aggrecan degradation. After induction of MMP-mediated aggrecan and collagen type II degradation, the chondrocytes had impaired repair capacity.
Effects of salbutamol on exhaled breath condensate biomarkers in acute lung injury: prospective analysis
Authors: Roca Oriol , Gómez-Ollés Susana , Cruz Maria-Jesús , Muñoz Xavier , Griffiths Mark JD , Masclans Joan R 
Published: May 2008

Abstract
Introduction
The benefits of β-adrenergic stimulation have been described in acute lung injury (ALI), but there is still no evidence of its anti-inflammatory effect in these patients. Biomarkers in exhaled breath condensate (EBC) were used to study the effects of salbutamol on lung inflammation in mechanically ventilated patients with ALI.

Methods
EBC was collected before and 30 minutes after administration of inhaled salbutamol (800 μg). The following parameters were measured in the samples: volume obtained, conductivity, pH after helium deaeration, and concentration of nitrites, nitrates and 8-isoprostane. The leukotriene B4 concentration was measured after sample lyophilization and reconstitution. Results are expressed as the median (interquartile range).

Results
EBC was obtained from six ALI patients, with a median age of 56 (46 to 76) years. At the time of EBC collection, the Lung Injury Score was 3 (2.3 to 3.1) and the PaO2/FIO2 ratio was 133 (96 to 211) mmHg. A significant increase in deaerated EBC pH was observed after salbutamol administration (7.66 (7.58 to 7.75) versus 7.83 (7.67 to 7.91), P = 0.028). Trends toward decreased nitrosative species (18.81 (13.33 to 49.44) μM versus 21.21 (8.07 to 29.83) μM, P = 0.173) and decreased 8-isoprostane concentration (11.64 (7.17 to 17.13) pg/ml versus 6.55 (4.03 to 9.99) pg/ml, P = 0.068) were detected. No changes in leukotriene B4 concentration were found (1.58 (0.47 to 3.57) pg/ml versus 2.06 (1.01 to 3.01) pg/ml, P = 0.753).

Conclusion
EBC analysis is a noninvasive technique that can be used to monitor ventilated patients. In EBC from a small cohort of patients with ALI, inhaled salbutamol significantly decreased airspace acidosis, a marker of inflammation, and was associated with a trend toward decreased markers of nitrosative and oxidative stress.
Commensal bacteria trigger a full dendritic cell maturation program that promotes the expansion of non-Tr1 suppressor T cells
Authors: Baba Nobuyasu , Samson Sandrine , Bourdet-Sicard Raphaëlle , Rubio Manuel , Sarfati Marika 
Published: May 2008

AbstractDendritic cells (DCs) orchestrate the immune response establishing immunity versus tolerance. These two opposite functions may be dictated by DC maturation status with maturity linked to immunogenicity. DCs directly interact with trillions of noninvasive intestinal bacteria in vivo, a process that contributes to gut homeostasis. We here evaluated the maturation program elicited in human DCs by direct exposure to commensal-related bacteria (CB) in the absence of inflammatory signals. We showed that eight gram+ and gram− CB strains up-regulated costimulatory molecule expression in DCs and provoked a chemokine receptor switch similar to that activated by gram+ pathogens. CB strains may be classified into three groups according to DC cytokine release: high IL-12 and low IL-10; low IL-12 and high IL-10; and low IL-12 and IL-10. All CB-treated DCs produced IL-1β and IL-6 and almost no TGF-β. Yet, CB instructed DCs to convert naive CD4+ T cells into hyporesponsive T cells that secreted low or no IFN-γ, IL-10, and IL-17 and instead, displayed suppressor function. These data demonstrate that phenotypic DC maturation combined to an appropriate cytokine profile is insufficient to warrant Th1, IL-10-secreting T regulatory Type 1 (Tr1), or Th17 polarization. We propose that commensal flora and as such, probiotics manipulate DCs by a yet-unidentified pathway to enforce gut tolerance.
Steroidogenic Factor 1 Regulates Expression of the Cannabinoid Receptor 1 in the Ventromedial Hypothalamic Nucleus
Authors: Kim Ki Woo , Jo Young-Hwan , Zhao Liping , Stallings Nancy R. , Chua Streamson C. , Parker Keith L. 
Published: May 2008

AbstractThe nuclear receptor steroidogenic factor 1 (SF-1) plays essential roles in the development and function of the ventromedial hypothalamic nucleus (VMH). Considerable evidence links the VMH and SF-1 with the regulation of energy homeostasis. Here, we demonstrate that SF-1 colocalizes in VMH neurons with the cannabinoid receptor 1 (CB1R) and that a specific CB1R agonist modulates electrical activity of SF-1 neurons in hypothalamic slice preparations. We further show that SF-1 directly regulates CB1R gene expression via a SF-1-responsive element at −101 in its 5′-flanking region. Finally, we show that knockout mice with selective inactivation of SF-1 in the brain have decreased expression of CB1R in the region of the VMH and exhibit a blunted response to systemically administered CB1R agonists. These studies suggest that SF-1 directly regulates the expression of CB1R, which has been implicated in the regulation of energy homeostasis and anxiety-like behavior.
Extensive apoptosis and abnormal morphogenesis in pro-caspase-3 transgenic zebrafish during development
Authors: Yamashita Michiaki , Mizusawa Nanami , Hojo Misako , Yabu Takeshi 
Published: May 2008

SUMMARYThe pro-apoptotic caspase-3 gene has been shown to have key functions in the execution of apoptosis (programmed cell death) in vertebrate cells. However, the central role of caspase-3 in morphogenesis during development remains unclear. In this study, transgenic zebrafish that overexpress full-length pro-caspase-3 were generated to determine the effects of caspase genes on vertebrate morphogenesis and stress tolerance. The enhanced expression of the full-length pro-caspase-3 cDNA induced extremely high levels of caspase activity and extensive apoptosis in the transgenic embryos, and 33–46% of F2 embyos in the transgenic lines exhibited some form of morphological abnormality. Pro-caspase-3 transgenic zebrafish exhibited abnormal morphogenesis in the eyes, notochord, heart and yolk sac, suggesting that enhanced processing of pro-caspase-3 triggers significant apoptotic responses in the specific target tissues that are undergoing morphogenesis during development. The transgenic fish had reduced eye size and showed degeneration of the retina, including the photoreceptor cell layers, whereas pigmentation and lens formation were not affected. In addition, heart failure due to a weakened heartbeat and reduced circulation was noted in the pro-caspase-3 transgenic embryos. The transgenic embryos were markedly sensitive to stress conditions, such as UV irradiation at 2 or 5 mJ cm–2. On the other hand, caspase-3 deficiency through injection of antisense morpholino oligo into embryos repressed apoptosis and enhanced stress tolerance after UV irradiation. Therefore, the caspase-3-mediated pro-apoptotic signalling pathway and its activation play critical roles in the induction of apoptosis and stress tolerance during zebrafish embryogenesis.
The role of proline in the elastic mechanism of hydrated spider silks
Authors: Savage Ken N. , Gosline John M. 
Published: May 2008

SUMMARYThis study used thermoelastic measurements to investigate the role of proline in the elastic mechanism of hydrated, spider major ampullate (MA) and flagelliform (FL) silks. Experiments on hydrated MA silk from Araneus diadematus (proline content 16%) reveal that conformational entropy elasticity accounts for about 90% of the elastic force at small extensions,but entropy elasticity drops to about half by 50% extension. The decrease in the entropic component with extension is due to the presence of relatively short and conformationally restricted network chains in Araneus MA silk. Experiments on hydrated Araneus FL silk (proline content 16%)indicate that entropy elasticity dominates the elastic mechanism up to extensions of 100% and beyond, which likely reflects the fact that the glycine-rich network chains in FL silk are longer and less conformationally restricted than those in the MA silk. Thus, the rubber-like, entropic elasticity of these two proline-rich silks is consistent with networks of amorphous chains that become mobile when hydrated. By contrast, the elastic mechanism of hydrated Nephila clavipes MA silk (proline content 3.5%)shows a small contribution from entropic elasticity for extensions of 5% or less, and by 10% extension the elastic force is due entirely to bond-energy elasticity, probably associated with the deformation of stable secondary structures. These results indicate that there are major differences in the structural organization of the glycine-rich network chains and the mechanism of elasticity in proline-rich and proline-deficient fibroins.