bluuebunny/crossref_metadata_2025_split huggingface dataset:
Impaired FANCD2 monoubiquitination and hypersensitivity to camptothecin uniquely characterize Fanconi anemia complementation group M
Authors: Singh Thiyam Ramsing , Bakker Sietske T. , Agarwal Sheba , Jansen Michael , Grassman Elke , Godthelp Barbara C. , Ali Abdullah Mahmood , Du Chang-hu , Rooimans Martin A. , Fan Qiang , Wahengbam Kebola , Steltenpool Jurgen , Andreassen Paul R. , Williams David A. , Joenje Hans , de Winter Johan P. , Meetei Amom Ruhikanta 
Published: May 2009

Abstract
FANCM is a component of the Fanconi anemia (FA) core complex and one FA patient (EUFA867) with biallelic mutations in FANCM has been described. Strikingly, we found that EUFA867 also carries biallelic mutations in FANCA. After correcting the FANCA defect in EUFA867 lymphoblasts, a “clean” FA-M cell line was generated. These cells were hypersensitive to mitomycin C, but unlike cells defective in other core complex members, FANCM−/− cells were proficient in monoubiquitinating FANCD2 and were sensitive to the topoisomerase inhibitor camptothecin, a feature shared only with the FA subtype D1 and N. In addition, FANCM−/− cells were sensitive to UV light. FANCM and a C-terminal deletion mutant rescued the cross-linker sensitivity of FANCM−/− cells, whereas a FANCM ATPase mutant did not. Because both mutants restored the formation of FANCD2 foci, we conclude that FANCM functions in an FA core complex–dependent and –independent manner.
Statistical identification of gene association by CID in application of constructing ER regulatory network
Authors: Liu Li-Yu D , Chen Chien-Yu , Chen Mei-Ju M , Tsai Ming-Shian , Lee Cho-Han S , Phang Tzu L , Chang Li-Yun , Kuo Wen-Hung , Hwa Hsiao-Lin , Lien Huang-Chun , Jung Shih-Ming , Lin Yi-Shing , Chang King-Jen , Hsieh Fon-Jou 
Published: May 2009

Abstract

Background
A variety of high-throughput techniques are now available for constructing comprehensive gene regulatory networks in systems biology. In this study, we report a new statistical approach for facilitating in silico inference of regulatory network structure. The new measure of association, coefficient of intrinsic dependence (CID), is model-free and can be applied to both continuous and categorical distributions. When given two variables X and Y, CID answers whether Y is dependent on X by examining the conditional distribution of Y given X. In this paper, we apply CID to analyze the regulatory relationships between transcription factors (TFs) (X) and their downstream genes (Y) based on clinical data. More specifically, we use estrogen receptor α (ERα) as the variable X, and the analyses are based on 48 clinical breast cancer gene expression arrays (48A).

Results
The analytical utility of CID was evaluated in comparison with four commonly used statistical methods, Galton-Pearson's correlation coefficient (GPCC), Student's t-test (STT), coefficient of determination (CoD), and mutual information (MI). When being compared to GPCC, CoD, and MI, CID reveals its preferential ability to discover the regulatory association where distribution of the mRNA expression levels on X and Y does not fit linear models. On the other hand, when CID is used to measure the association of a continuous variable (Y) against a discrete variable (X), it shows similar performance as compared to STT, and appears to outperform CoD and MI. In addition, this study established a two-layer transcriptional regulatory network to exemplify the usage of CID, in combination with GPCC, in deciphering gene networks based on gene expression profiles from patient arrays.

Conclusion
CID is shown to provide useful information for identifying associations between genes and transcription factors of interest in patient arrays. When coupled with the relationships detected by GPCC, the association predicted by CID are applicable to the construction of transcriptional regulatory networks. This study shows how information from different data sources and learning algorithms can be integrated to investigate whether relevant regulatory mechanisms identified in cell models can also be partially re-identified in clinical samples of breast cancers.

Availability
the implementation of CID in R codes can be freely downloaded from http://homepage.ntu.edu.tw/~lyliu/BC/.
Improving Gene-finding in Chlamydomonas reinhardtii:GreenGenie2
Authors: Kwan Alan L , Li Linya , Kulp David C , Dutcher Susan K , Stormo Gary D 
Published: May 2009

Abstract

Background
The availability of whole-genome sequences allows for the identification of the entire set of protein coding genes as well as their regulatory regions. This can be accomplished using multiple complementary methods that include ESTs, homology searches and ab initio gene predictions. Previously, the Genie gene-finding algorithm was trained on a small set of Chlamydomonas genes and shown to improve the accuracy of gene prediction in this species compared to other available programs. To improve ab initio gene finding in Chlamydomonas, we assemble a new training set consisting of over 2,300 cDNAs by assembling over 167,000 Chlamydomonas EST entries in GenBank using the EST assembly tool PASA.

Results
The prediction accuracy of our cDNA-trained gene-finder, GreenGenie2, attains 83% sensitivity and 83% specificity for exons on short-sequence predictions. We predict about 12,000 genes in the version v3 Chlamydomonas genome assembly, most of which (78%) are either identical to or significantly overlap the published catalog of Chlamydomonas genes [1]. 22% of the published catalog is absent from the GreenGenie2 predictions; there is also a fraction (23%) of GreenGenie2 predictions that are absent from the published gene catalog. Randomly chosen gene models were tested by RT-PCR and most support the GreenGenie2 predictions.

Conclusion
These data suggest that training with EST assemblies is highly effective and that GreenGenie2 is a valuable, complementary tool for predicting genes in Chlamydomonas reinhardtii.
Water deficit alters differentially metabolic pathways affecting important flavor and quality traits in grape berries of Cabernet Sauvignon and Chardonnay
Authors: Deluc Laurent G , Quilici David R , Decendit Alain , Grimplet Jérôme , Wheatley Matthew D , Schlauch Karen A , Mérillon Jean-Michel , Cushman John C , Cramer Grant R 
Published: May 2009

AbstractBackgroundWater deficit has significant effects on grape berry composition resulting in improved wine quality by the enhancement of color, flavors, or aromas. While some pathways or enzymes affected by water deficit have been identified, little is known about the global effects of water deficit on grape berry metabolism.ResultsThe effects of long-term, seasonal water deficit on berries of Cabernet Sauvignon, a red-wine grape, and Chardonnay, a white-wine grape were analyzed by integrated transcript and metabolite profiling. Over the course of berry development, the steady-state transcript abundance of approximately 6,000 Unigenes differed significantly between the cultivars and the irrigation treatments. Water deficit most affected the phenylpropanoid, ABA, isoprenoid, carotenoid, amino acid and fatty acid metabolic pathways. Targeted metabolites were profiled to confirm putative changes in specific metabolic pathways. Water deficit activated the expression of numerous transcripts associated with glutamate and proline biosynthesis and some committed steps of the phenylpropanoid pathway that increased anthocyanin concentrations in Cabernet Sauvignon. In Chardonnay, water deficit activated parts of the phenylpropanoid, energy, carotenoid and isoprenoid metabolic pathways that contribute to increased concentrations of antheraxanthin, flavonols and aroma volatiles. Water deficit affected the ABA metabolic pathway in both cultivars. Berry ABA concentrations were highly correlated with 9-cis-epoxycarotenoid dioxygenase (NCED1) transcript abundance, whereas the mRNA expression of otherNCEDgenes and ABA catabolic and glycosylation processes were largely unaffected. Water deficit nearly doubled ABA concentrations within berries of Cabernet Sauvignon, whereas it decreased ABA in Chardonnay at véraison and shortly thereafter.ConclusionThe metabolic responses of grapes to water deficit varied with the cultivar and fruit pigmentation. Chardonnay berries, which lack any significant anthocyanin content, exhibited increased photoprotection mechanisms under water deficit conditions. Water deficit increased ABA, proline, sugar and anthocyanin concentrations in Cabernet Sauvignon, but not Chardonnay berries, consistent with the hypothesis that ABA enhanced accumulation of these compounds. Water deficit increased the transcript abundance of lipoxygenase and hydroperoxide lyase in fatty metabolism, a pathway known to affect berry and wine aromas. These changes in metabolism have important impacts on berry flavor and quality characteristics. Several of these metabolites are known to contribute to increased human-health benefits.
Evaluation of the passage of Lactobacillus gasseri K7 and bifidobacteria from the stomach to intestines using a single reactor model
Authors: Ritter Philipp , Kohler Christian , von Ah Ueli 
Published: May 2009

Abstract

Background
Probiotic bacteria are thought to play an important role in the digestive system and therefore have to survive the passage from stomach to intestines. Recently, a novel approach to simulate the passage from stomach to intestines in a single bioreactor was developed. The advantage of this automated one reactor system was the ability to test the influence of acid, bile salts and pancreatin.

Lactobacillus gasseri K7 is a strain isolated from infant faeces with properties making the strain interesting for cheese production. In this study, a single reactor system was used to evaluate the survival of L. gasseri K7 and selected bifidobacteria from our collection through the stomach-intestine passage.

Results
Initial screening for acid resistance in acidified culture media showed a low tolerance of Bifidobacterium dentium for this condition indicating low survival in the passage. Similar results were achieved with B. longum subsp. infantis whereas B. animalis subsp. lactis had a high survival.
These initial results were confirmed in the bioreactor model of the stomach-intestine passage. B. animalis subsp. lactis had the highest survival rate (10%) attaining approximately 5 × 106 cfu ml-1 compared to the other tested bifidobacteria strains which were reduced by a factor of up to 106. Lactobacillus gasseri K7 was less resistant than B. animalis subsp. lactis but survived at cell concentrations approximately 1000 times higher than other bifidobacteria.

Conclusion
In this study, we were able to show that L. gasseri K7 had a high survival rate in the stomach-intestine passage. By comparing the results with a previous study in piglets we could confirm the reliability of our simulation. Of the tested bifidobacteria strains, only B. animalis subsp. lactis showed acceptable survival for a successful passage in the simulation system.
A case-control study on the combined effects of p53 and p73 polymorphisms on head and neck cancer risk in an Italian population
Authors: Gallì Paola , Cadoni Gabriella , Volante Mariangela , De Feo Emma , Amore Rosarita , Giorgio Arianna , Arzani Dario , Paludetti Gaetano , Ricciardi Gualtiero , Boccia Stefania 
Published: May 2009

AbstractBackgroundThe purpose of this study is to analyze the combined effects of selectedp53 andp73 polymorphisms and their interaction with lifestyle habits on squamous cell carcinoma of the head and neck (SCCHN) risk and progression in an Italian population.MethodsTwo hundred and eighty-three cases and 295 hospital controls were genotyped forp53 polymorphisms on exon 4 (Arg72Pro), intron 3 and 6, andp73 G4C14-to-A4T14. Their association with SCCHN was estimated using a logistic regression analysis, while a multinomial logistic regression approach was applied to calculate the effect of the selected polymorphisms on SCCHN different sites (oral cavity, oropharynx, hypopharynx and larynx). We performed an haplotype analysis of thep53 polymorphisms, and a gene-gene interaction analysis for the combined effects ofp73 G4C14-to-A4T14 andp53 polymorphisms.ResultsWe found a significant increased risk of SCCHN among individuals with combinedp73 exon 2 G4A andp53 intron 3 variant alleles (OR = 2.22, 95% CI: 1.08–4.56), and a protective effect for those carrying thep53 exon 4-p53 intron 6 diplotype combination (OR = 0.67; 95% CI: 0.47–0.92). From the gene-environment interaction analysis we found that individuals aged < 45 years carryingp73 exon 2 G4A variant allele have a 12.85-increased risk of SCCHN (95% CI: 2.10–78.74) compared with persons of the same age with the homozygous wild type genotype. Improved survival rate was observed amongp53 intron 6 variant allele carriers (Hazard Ratio = 0.51 (95% CI: 0.23–1.16).ConclusionOur study provides for the first time evidence that individuals carryingp53 exon 4 andp53 intron 6 variant alleles are significantly protected against SCCHN, and also shows that an additional risk is conferred by the combination ofp73 exon 2 G4C14-to-A4T14 andp53 intron 3 variant allele. Larger studies are required to confirm these findings.
Hydrodebridement of wounds: effectiveness in reducing wound bacterial contamination and potential for air bacterial contamination
Authors: Bowling Frank L , Stickings Daryl S , Edwards‐Jones Valerie , Armstrong David G , Boulton Andrew JM 
Published: May 2009

AbstractBackgroundThe purpose of this study was to assess the level of air contamination with bacteria after surgical hydrodebridement and to determine the effectiveness of hydro surgery on bacterial reduction of a simulated infected wound.MethodsFour porcine samples were scored then infected with a broth culture containing a variety of organisms and incubated at 37°C for 24 hours. The infected samples were then debrided with the hydro surgery tool (Versajet, Smith and Nephew, Largo, Florida, USA). Samples were taken for microbiology, histology and scanning electron microscopy pre‐infection, post infection and post debridement. Air bacterial contamination was evaluated before, during and after debridement by using active and passive methods; for active sampling the SAS‐Super 90 air sampler was used, for passive sampling settle plates were located at set distances around the clinic room.ResultsThere was no statistically significant reduction in bacterial contamination of the porcine samples post hydrodebridement. Analysis of the passive sampling showed a significant (p < 0.001) increase in microbial counts post hydrodebridement. Levels ranging from 950 colony forming units per meter cubed (CFUs/m3) to 16780 CFUs/m3 were observed with active sampling of the air whilst using hydro surgery equipment compared with a basal count of 582 CFUs/m3. During removal of the wound dressing, a significant increase was observed relative to basal counts (p < 0.05). Microbial load of the air samples was still significantly raised 1 hour post‐therapy.ConclusionThe results suggest a significant increase in bacterial air contamination both by active sampling and passive sampling. We believe that action might be taken to mitigate fallout in the settings in which this technique is used.
Hypoxia upregulates angiogenesis and synovial cell migration in rheumatoid arthritis
Authors: Akhavani Mohammed A , Madden Leigh , Buysschaert Ian , Sivakumar Branavan , Kang Norbert , Paleolog Ewa M 
Published: May 2009

Abstract
Introduction
Rheumatoid arthritis (RA) is characterised by invasion of cartilage, bone and tendon by inflamed synovium. Previous studies in our laboratory have shown that hypoxia is a feature of RA synovitis. In the present study, we investigated the consequences of hypoxia on angiogenesis and synovial fibroblast migration in RA.

Methods
Synovial tissue was harvested from RA patients, and synovial membrane cells were cultured under conditions either of hypoxia (1% oxygen) or normoxia (21% oxygen). Protein levels of matrix metalloproteinases (MMPs) and angiogenic factors were measured, while RNA was extracted for PCR quantification of MMPs/tissue inhibitors of MMP (TIMPs) and angiogenic factors. Migration of RA synovial fibroblasts through collagen, and the effect of RA synovial cell supernatants in an in vitro angiogenesis assay, were utilised to determine the functional relevance of changes in mRNA/protein.

Results
We observed upregulation under hypoxic conditions of MMPs responsible for collagen breakdown, specifically collagenase MMP-8, and the gelatinases MMP-2 and MMP-9, at both mRNA and protein levels. Increased MT1-MMP mRNA was also observed, but no effect on TIMP-1 or TIMP-2 was detected. RA fibroblast migration across collagen was significantly increased under hypoxic conditions, and was dependent on MMP activity. Furthermore, expression of angiogenic stimuli, such as vascular endothelial growth factor (VEGF), and VEGF/placental growth factor heterodimer, was also increased. Crucially, we show for the first time that hypoxia increased the angiogenic drive of RA cells, as demonstrated by enhanced blood vessel formation in an in vitro angiogenesis assay.

Conclusions
Hypoxia may be responsible for rendering RA synovial lining proangiogenic and proinvasive, thus leading to the debilitating features characteristic of RA.
Regulation of Oxytocin Receptor Responsiveness by G Protein-Coupled Receptor Kinase 6 in Human Myometrial Smooth Muscle
Authors: Willets Jonathon M. , Brighton Paul J. , Mistry Rajendra , Morris Gavin E. , Konje Justin C. , Challiss R. A. John 
Published: May 2009

AbstractOxytocin plays an important role in the progression, timing, and modulation of uterine contraction during labor and is widely used as an uterotonic agent. We investigated the mechanisms regulating oxytocin receptor (OTR) signaling in human primary myometrial smooth muscle cells and the ULTR cell-line. Oxytocin produced concentration-dependent increases in both total [3H]inositol phosphate accumulation and intracellular Ca2+ concentration ([Ca2+]i); however, responses were greater and more reproducible in the ULTR cell line. Assessment of phospholipase C activity in single cells revealed that the OTR desensitizes rapidly (within 5 min) in the presence of oxytocin (100 nm). To characterize OTR desensitization further, cells were stimulated with a maximally effective concentration of oxytocin (100 nm, 30 sec) followed by a variable washout period and a second identical application of oxytocin. This brief exposure to oxytocin caused a marked decrease (&gt;70%) in OTR responsiveness to rechallenge and was fully reversed by increasing the time period between agonist challenges. To assess involvement of G protein-coupled receptor kinases (GRKs) in OTR desensitization, cells were transfected with small interfering RNAs to cause specific ≥75% knockdown of GRKs 2, 3, 5, or 6. In both primary myometrial and ULTR cells, knockdown of GRK6 largely prevented oxytocin-induced OTR desensitization; in contrast, selective depletion of GRKs 2, 3, or 5 was without effect. These data indicate that GRK6 recruitment is a cardinal effector of OTR responsiveness and provide mechanistic insight into the likely in vivo regulation of OTR signaling in uterine smooth muscle.
Social phobia and sexual problems: A comparison of social phobic, sexually dysfunctional and normal individuals
Authors: Munoz Valentina , Stravynski Ariel 
Published: May 2009

Objectives. This study sought to test the putative link between social phobia and sexual functioning.Methods. Three groups consisting of 106 social phobic, 164 sexually dysfunctional and 111 normal participants were assessed in terms of sexual functioning, social anxiety, social functioning and general psychopathology.Results. Although social phobic men were less sexually active than normal men, they were as sexually satisfied. Social phobic women were alike their normal counterparts in all respects.Conclusions. Overall, social phobic individuals were not more prone to report sexual problems than normal individuals despite reporting the severest levels of social anxiety. Theoretically, our results are best understood as supporting an interpersonal conception of social phobia and a related socio‐cultural perspective regarding sexual roles.
The persecution and deservedness scale
Authors: Melo Sara , Corcoran Rhiannon , Shryane Nick , Bentall Richard P. 
Published: May 2009

Objectives. To design a brief measure to assess both the severity of paranoid thinking and the perceived deservedness of persecution, which can be employed in clinical and non‐clinical populations.Background. No existing measure is adequate for these purposes.Methods. In Study 1, we selected 10 items for a persecution and deservedness scale (PaDS) using data from 318 UK and 290 Portuguese undergraduate students, who also completed the Beck Depression Inventory and the Fenigstein's Paranoia Scale. In Study 2, we made comparisons between 45 clinical participants with a diagnosis of schizophrenia, schizoaffective disorder or delusional disorder and the UK students from Study 1. The psychometric properties of the PaDS were analysed for separate persecution (P) and deservedness (D) subscales.Results. The 10‐item PaDS subscales were internally reliable for both clinical and student samples. Correlations with other measures of depressive mood and paranoid thinking indicate that the P subscale has concurrent validity. Higher P and D scores were observed in UK students compared to Portuguese students. The clinical participants' P scores subscale were significantly higher than the students' scores but their D scores were lower.Conclusions. The PaDS is a reliable and valid measure of paranoid thinking and perceived deservedness of persecution, which is sensitive for use in clinical and non‐clinical populations. Paranoid thinking appears to be mainly bad‐me in non‐clinical groups but poor‐me in psychotic psychiatric patients.
Labordiagnostik in der Prävention, Differentialdiagnose und Verlaufskontrolle der Osteoporose / Laboratory diagnostics in the prevention, differential diagnosis and monitoring of osteoporosis
Authors: Anliker Markus , Bieglmayer Christian , Dimai Hans Peter , Gasser Rudolf Wolfgang , Kudlacek Stefan , Obermayer-Pietsch Barbara , Schmidt-Gayk Heinrich , Sottara Elke , Woloszczuk Wolfgang , Zwettler Elisabeth , Griesmacher Andrea 
Published: May 2009

Zusammenfassung
Osteoporose wird von der WHO zu den ökonomisch bedeutsamsten Erkrankungen des 21. Jahrhunderts gezählt. Abgesehen von Anamnese, klinischer Untersuchung und bildgebenden Verfahren sind Laboruntersuchungen wichtige Werkzeuge in der Diagnose, Therapieüberwachung und Verlaufskontrolle der Osteoporose. Man unterscheidet Basis-Laboruntersuchungen von weiterführenden Laboruntersuchungen. Das Basislabor dient zur Differentialdiagnose zwischen primären und sekundären Formen der Osteoporose. Ursachen der sekundären Formen der Osteoporose müssen unter anderem durch weiterführende Untersuchungen abgeklärt werden. Spezielle Biomarker des Knochenstoffwechsels werden hauptsächlich zur Therapieüberwachung und Verlaufsbeurteilung der Osteoporose genutzt.
Crack Mouth Opening Displacement-Based η Factors for SE(B) Specimens
Authors: Petti J. P. , Dodds, Jr. R. H. , Link R. E. 
Published: May 2009

Abstract
Three-dimensional finite element analysis of SE(B) fracture toughness specimens with crack sizes ranging from a/W=0.1–0.6 were performed to develop ηCMOD values for estimating Jpl in fracture toughness tests. The analyses included specimens with smooth sides and 20 % sidegrooves. The results for ηCMOD were 4–9 % lower than previously published results based on two-dimensional plane strain analysis. A simple linear expression for ηCMOD(a/W) was proposed for introduction into ASTM E1820 for calculating Jpl in SE(B) specimens with 0.05≤a/W≤0.7.