bluuebunny/crossref_metadata_2025_split huggingface dataset:
TGFβ signaling plays a critical role in promoting alternative macrophage activation
Authors: Gong Dapeng , Shi Wei , Yi Sun-ju , Chen Hui , Groffen John , Heisterkamp Nora 
Published: June 2012

AbstractBackgroundUpon stimulation with different cytokines, macrophages can undergo classical or alternative activation to become M1 or M2 macrophages. Alternatively activated (or M2) macrophages are defined by their expression of specific gene products and play an important role in containing inflammation, removing apoptotic cells and repairing tissue damage. Whereas it is well-established that IL-4 can drive alternative activation, if lack of TGFβ signaling at physiological levels affects M2 polarization has not been addressed.ResultsVav1-Cre x TβRIIfx/fxmice, lacking TβRII function in hematopoietic cells, exhibited uncontrolled pulmonary inflammation and developed a lethal autoimmune syndrome at young age. This was accompanied by significantly increased numbers of splenic neutrophils and T cells as well as elevated hepatic macrophage infiltration and bone marrow monocyte counts.TβRII-/-CD4+and CD8+T-cells in the lymph nodes and spleen expressed increased cell surface CD44, and CD69 was also higher on CD4+lymph node T-cells. Loss of TβRII in bone marrow-derived macrophages (BMDMs) did not affect the ability of these cells to perform efferocytosis. However, these cells were defective in basal and IL-4-inducedarg1mRNA and Arginase-1 protein production. Moreover, the transcription of genes that are typically upregulated in M2-polarized macrophages, such asym1, mcr2 and mgl2,was also decreased in peritoneal macrophages and IL-4-stimulatedTβRII-/-BMDMs. We found that cell surface and mRNA expression of Galectin-3, which also regulates M2 macrophage polarization, was lower inTβRII-/-BMDMs. Very interestingly, the impaired ability of these null mutant BMDMs to differentiate into IL-4 polarized macrophages was Stat6- and Smad3-independent, but correlated with reduced levels of phospho-Akt and β-catenin.ConclusionsOur results establish a novel biological role for TGFβ signaling in controlling expression of genes characteristic for alternatively activated macrophages. We speculate that lack of TβRII signaling reduces the anti-inflammatory M2 phenotype of macrophages because of reduced expression of these products. This would cause defects in the ability of the M2 macrophages to negatively regulate other immune cells such as T-cells in the lung, possibly explaining the systemic inflammation observed inVav1-Cre x TβRIIfx/fxmice.
Interaction of C/EBP-beta and NF-Y factors constrains activity levels of the nutritionally controlled promoter IA expressing the acetyl-CoA carboxylase-alpha gene in cattle
Authors: Shi Xuanming , Metges Cornelia C , Seyfert Hans-Martin 
Published: June 2012

Abstract

Background
The enzyme acetyl-CoA carboxylase-alpha (ACC-α) is rate limiting for de novo fatty acid synthesis. Among the four promoters expressing the bovine gene, promoter IA (PIA) is dominantly active in lipogenic tissues. This promoter is in principal repressed but activated under favorable nutritional conditions. Previous analyses already coarsely delineated the repressive elements on the distal promoter but did not resolve the molecular nature of the repressor. Knowledge about the molecular functioning of this repressor is fundamental to understanding the nutrition mediated regulation of PIA activity. We analyzed here the molecular mechanism calibrating PIA activity.

Results
We finely mapped the repressor binding sites in reporter gene assays and demonstrate together with Electrophoretic Mobility Shift Assays that nuclear factor-Y (NF-Y) and CCAAT/enhancer binding protein-β(C/EBPβ) each separately repress PIA activity by binding to their cognate low affinity sites, located on distal elements of the promoter. Simultaneous binding of both factors results in strongest repression. Paradoxically, over expression of NFY factors, but also - and even more so - of C/EBPβ significantly activated the promoter when bound to high affinity sites on the proximal promoter. However, co-transfection experiments revealed that NF-Y may eventually diminish the strong stimulatory effect of C/EBPβ at the proximal PIA in a dose dependent fashion. We validated by chromatin immunoprecipitation, that NF-Y and C/EBP factors may physically interact.

Conclusion
The proximal promoter segment of PIA appears to be principally in an active state, since even minute concentrations of both, NF-Y and C/EBPβ factors can saturate the high affinity activator sites. Higher factor concentrations will saturate the low affinity repressive sites on the distal promoter resulting in reduced and calibrated promoter activity. Based on measurements of the mRNA concentrations of those factors in different tissues we propose that the interplay of both factors may set tissue-specific limits for PIA activity.
Modulations of neural activity in auditory streaming caused by spectral and temporal alternation in subsequent stimuli: a magnetoencephalographic study
Authors: Chakalov Ivan , Draganova Rossitza , Wollbrink Andreas , Preissl Hubert , Pantev Christo 
Published: June 2012

Abstract

Background
The aim of the present study was to identify a specific neuronal correlate underlying the pre-attentive auditory stream segregation of subsequent sound patterns alternating in spectral or temporal cues. Fifteen participants with normal hearing were presented with series’ of two consecutive ABA auditory tone-triplet sequences, the initial triplets being the Adaptation sequence and the subsequent triplets being the Test sequence. In the first experiment, the frequency separation (delta-f) between A and B tones in the sequences was varied by 2, 4 and 10 semitones. In the second experiment, a constant delta-f of 6 semitones was maintained but the Inter-Stimulus Intervals (ISIs) between A and B tones were varied. Auditory evoked magnetic fields (AEFs) were recorded using magnetoencephalography (MEG). Participants watched a muted video of their choice and ignored the auditory stimuli. In a subsequent behavioral study both MEG experiments were replicated to provide information about the participants’ perceptual state.

Results
MEG measurements showed a significant increase in the amplitude of the B-tone related P1 component of the AEFs as delta-f increased. This effect was seen predominantly in the left hemisphere. A significant increase in the amplitude of the N1 component was only obtained for a Test sequence delta-f of 10 semitones with a prior Adaptation sequence of 2 semitones. This effect was more pronounced in the right hemisphere. The additional behavioral data indicated an increased probability of two-stream perception for delta-f = 4 and delta-f = 10 semitones with a preceding Adaptation sequence of 2 semitones. However, neither the neural activity nor the perception of the successive streaming sequences were modulated when the ISIs were alternated.

Conclusions
Our MEG experiment demonstrated differences in the behavior of P1 and N1 components during the automatic segregation of sounds when induced by an initial Adaptation sequence. The P1 component appeared enhanced in all Test-conditions and thus demonstrates the preceding context effect, whereas N1 was specifically modulated only by large delta-f Test sequences induced by a preceding small delta-f Adaptation sequence. These results suggest that P1 and N1 components represent at least partially-different systems that underlie the neural representation of auditory streaming.
Genome-wide identification of differentially expressed genes under water deficit stress in upland cotton (Gossypium hirsutum L.)
Authors: Park Wonkeun , Scheffler Brian E , Bauer Philip J , Campbell B Todd 
Published: June 2012

AbstractBackgroundCotton is the world’s primary fiber crop and is a major agricultural commodity in over 30 countries. Like many other global commodities, sustainable cotton production is challenged by restricted natural resources. In response to the anticipated increase of agricultural water demand, a major research direction involves developing crops that use less water or that use water more efficiently. In this study, our objective was to identify differentially expressed genes in response to water deficit stress in cotton. A global expression analysis using cDNA-Amplified Fragment Length Polymorphism was conducted to compare root and leaf gene expression profiles from a putative drought resistant cotton cultivar grown under water deficit stressed and well watered field conditions.ResultsWe identified a total of 519 differentially expressed transcript derived fragments. Of these, 147 transcript derived fragment sequences were functionally annotated according to their gene ontology. Nearly 70 percent of transcript derived fragments belonged to four major categories: 1) unclassified, 2) stress/defense, 3) metabolism, and 4) gene regulation. We found heat shock protein-related and reactive oxygen species-related transcript derived fragments to be among the major parts of functional pathways induced by water deficit stress. Also, twelve novel transcripts were identified as both water deficit responsive and cotton specific. A subset of differentially expressed transcript derived fragments was verified using reverse transcription-polymerase chain reaction. Differential expression analysis also identified five pairs of duplicated transcript derived fragments in which four pairs responded differentially between each of their two homologues under water deficit stress.ConclusionsIn this study, we detected differentially expressed transcript derived fragments from water deficit stressed root and leaf tissues in tetraploid cotton and provided their gene ontology, functional/biological distribution, and possible roles of gene duplication. This discovery demonstrates complex mechanisms involved with polyploid cotton’s transcriptome response to naturally occurring field water deficit stress. The genes identified in this study will provide candidate targets to manipulate the water use characteristics of cotton at the molecular level.
Capsule colonoscopy increases uptake of colorectal cancer screening
Authors: Groth Stefan , Krause Horst , Behrendt Rainer , Hill Helge , Börner Michael , Bastürk Murat , Plathner Nora , Schütte Friedrich , Gauger Ulrich , Riemann Jürgen Ferdinand , Altenhofen Lutz , Rösch Thomas 
Published: June 2012

Abstract

Background
Screening colonoscopy effectiveness is hampered by limited adherence by the general population. The present prospective study was performed to evaluate whether adding capsule colonoscopy to the endoscopic screening options increases uptake.

Methods
Invitation letters were sent to 2150 persons above the age of 55 insured with a German medical insurance company in the area of Rinteln, Lower Saxony with a baseline spontaneous annual screening colonoscopy uptake of 1 %. Both capsule or conventional colonoscopy were offered. Interested persons were given information about the two screening options by four local gastroenterologists and examinations were then performed according to screenees’ final choice.

Results
154 persons sought further information, and 34 and 90 underwent conventional and capsule colonoscopy, respectively. Colonoscopy uptake was thus increased by the invitation process by 60 % (1.6 % vs. 1 %; p = 0.075), while the option of capsule endoscopy led to a fourfold increase of screening uptake (4.2 % vs. 1 %, p < 0.001). Despite similar age distribution in both sex groups, uptake in men was significantly higher (5.6 % vs. 2.8 %, p = 002). However, overall adenoma yield was not different in both groups.

Conclusions
The present study suggests that offering the option of capsule colonoscopy increases uptake of endoscopic colorectal cancer screening. However, capsule endoscopy sensitivity for adenoma detection needs to be improved.
Predictors of human papillomavirus infection in women undergoing routine cervical cancer screening in Spain: the CLEOPATRE study
Authors: Roura Esther , Iftner Thomas , Vidart José Antonio , Kjaer Susanne Krüger , Bosch F Xavier , Muñoz Nubia , Palacios Santiago , Rodriguez Maria San Martin , Morillo Carmen , Serradell Laurence , Torcel-Pagnon Laurence , Cortes Javier , Castellsagué Xavier ,   the CLEOPATRE Spain Study Group
Published: June 2012

Abstract

Background
Human papillomavirus (HPV) is a sexually transmitted infection that may lead to development of precancerous and cancerous lesions of the cervix. The aim of the current study was to investigate socio-demographic, lifestyle, and medical factors for potential associations with cervical HPV infection in women undergoing cervical cancer screening in Spain.

Methods
The CLEOPATRE Spain study enrolled 3 261 women aged 18–65 years attending cervical cancer screening across the 17 Autonomous Communities. Liquid-based cervical samples underwent cytological examination and HPV testing. HPV positivity was determined using the Hybrid Capture II assay, and HPV genotyping was conducted using the INNO-LiPA HPV Genotyping Extra assay. Multivariate logistic regression was used to identify putative risk factors for HPV infection.

Results
A lifetime number of two or more sexual partners, young age (18–25 years), a history of genital warts, and unmarried status were the strongest independent risk factors for HPV infection of any type. Living in an urban community, country of birth other than Spain, low level of education, and current smoking status were also independent risk factors for HPV infection. A weak inverse association between condom use and HPV infection was observed. Unlike monogamous women, women with two or more lifetime sexual partners showed a lower risk of infection if their current partner was circumcised (P for interaction, 0.005) and a higher risk of infection if they were current smokers (P for interaction, 0.01).

Conclusion
This is the first large-scale, country-wide study exploring risk factors for cervical HPV infection in Spain. The data strongly indicate that variables related to sexual behavior are the main risk factors for HPV infection. In addition, in non-monogamous women, circumcision of the partner is associated with a reduced risk and smoking with an increased risk of HPV infection.
Steroid receptor coactivators, HER-2 and HER-3 expression is stimulated by tamoxifen treatment in DMBA-induced breast cancer
Authors: Moi Line L Haugan , Flågeng Marianne Hauglid , Gjerde Jennifer , Madsen Andre , Røst Therese Halvorsen , Gudbrandsen Oddrun Anita , Lien Ernst A , Mellgren Gunnar 
Published: June 2012

Abstract

Background
Steroid receptor coactivators (SRCs) may modulate estrogen receptor (ER) activity and the response to endocrine treatment in breast cancer, in part through interaction with growth factor receptor signaling pathways. In the present study the effects of tamoxifen treatment on the expression of SRCs and human epidermal growth factor receptors (HERs) were examined in an animal model of ER positive breast cancer.

Methods
Sprague-Dawley rats with DMBA-induced breast cancer were randomized to 14 days of oral tamoxifen 40 mg/kg bodyweight/day or vehicle only (controls). Tumors were measured throughout the study period. Blood samples and tumor tissue were collected at sacrifice and tamoxifen and its main metabolites were quantified using LC-MS/MS. The gene expression in tumor of SRC-1, SRC-2/transcription intermediary factor-2 (TIF-2), SRC-3/amplified in breast cancer 1 (AIB1), ER, HER-1, -2, -3 and HER-4, as well as the transcription factor Ets-2, was measured by real-time RT-PCR. Protein levels were further assessed by Western blotting.

Results
Tamoxifen and its main metabolites were detected at high concentrations in serum and accumulated in tumor tissue in up to tenfolds the concentration in serum. Mean tumor volume/rat decreased in the tamoxifen treated group, but continued to increase in controls. The mRNA expression levels of SRC-1 (P = 0.035), SRC-2/TIF-2 (P = 0.002), HER-2 (P = 0.035) and HER-3 (P = 0.006) were significantly higher in tamoxifen treated tumors compared to controls, and the results were confirmed at the protein level using Western blotting. SRC-3/AIB1 protein was also higher in tamoxifen treated tumors. SRC-1 and SRC-2/TIF-2 mRNA levels were positively correlated with each other and with HER-2 (P ≤ 0.001), and the HER-2 mRNA expression correlated with the levels of the other three HER family members (P < 0.05). Furthermore, SRC-3/AIB1 and HER-4 were positively correlated with each other and Ets-2 (P < 0.001).

Conclusions
The expression of SRCs and HER-2 and -3 is stimulated by tamoxifen treatment in DMBA-induced breast cancer. Stimulation and positive correlation of coactivators and HERs may represent an early response to endocrine treatment. The role of SRCs and HER-2 and -3 should be further studied in order to evaluate their effects on response to long-term tamoxifen treatment.
Colon cancer molecular subtypes identified by expression profiling and associatedto stroma, mucinous type and different clinical behavior
Authors: Perez Villamil Beatriz , Romera Lopez Alejandro , Hernandez Prieto Susana , Lopez Campos Guillermo , Calles Antonio , Lopez Asenjo Jose Antonio , Sanz Ortega Julian , Fernandez Perez Cristina , Sastre Javier , Alfonso Rosario , Caldes Trinidad , Martin Sanchez Fernando , Diaz Rubio Eduardo 
Published: June 2012

AbstractBackgroundColon cancer patients with the same stage show diverse clinical behavior dueto tumor heterogeneity. We aimed to discover distinct classes of tumorsbased on microarray expression patterns, to analyze whether the molecularclassification correlated with the histopathological stages or otherclinical parameters and to study differences in the survival.MethodsHierarchical clustering was performed for class discovery in 88 colon tumors(stages I to IV). Pathways analysis and correlations between clinicalparameters and our classification were analyzed. Tumor subtypes werevalidated using an external set of 78 patients. A 167 gene signatureassociated to the main subtype was generated using the 3-Nearest-Neighbormethod. Coincidences with other prognostic predictors were assesed.ResultsHierarchical clustering identified four robust tumor subtypes withbiologically and clinically distinct behavior. Stromal components(p < 0.001), nuclear β-catenin (p = 0.021),mucinous histology (p = 0.001), microsatellite-instability(p = 0.039) and BRAF mutations (p < 0.001) wereassociated to this classification but it was independent of Dukes stages(p = 0.646). Molecular subtypes were established from stage I.High-stroma-subtype showed increased levels of genes and altered pathwaysdistinctive of tumour-associated-stroma and components of the extracellularmatrix in contrast to Low-stroma-subtype. Mucinous-subtype was reflected bythe increased expression of trefoil factors and mucins as well as by ahigher proportion of MSI andBRAFmutations. Tumor subtypes werevalidated using an external set of 78 patients. A 167 gene signatureassociated to the Low-stroma-subtype distinguished low risk patients fromhigh risk patients in the external cohort (Dukes B andC:HR = 8.56(2.53-29.01); Dukes B,C andD:HR = 1.87(1.07-3.25)). Eight different reported survival genesignatures segregated our tumors into two groups the Low-stroma-subtype andthe other tumor subtypes.ConclusionsWe have identified novel molecular subtypes in colon cancer with distinctbiological and clinical behavior that are established from the initiation ofthe tumor. Tumor microenvironment is important for the classification andfor the malignant power of the tumor. Differential gene sets and biologicalpathways characterize each tumor subtype reflecting underlying mechanisms ofcarcinogenesis that may be used for the selection of targeted therapeuticprocedures. This classification may contribute to an improvement in themanagement of the patients with CRC and to a more comprehensiveprognosis.
Horizontal equity and mental health care: a study of priority ratings by clinicians and teams at outpatient clinics
Authors: Holman Per Arne , Ruud Torleif , Grepperud Sverre 
Published: June 2012

Abstract

Background
In Norway, admission teams at Community Mental Health Centres (CMHCs) assess referrals from General Practitioners (GPs), and classify the referrals into priority groups according to treatment needs, as defined in the Act of Patient Rights. In this study, we analyzed classification of similar referrals to determine the reliability of classification into priority groups (i.e., horizontal equity).

Methods
Twenty anonymous case vignettes based on representative referrals were classified by 42 admission team members at 16 CMHCs in the South-East Health Region of Norway. All clinicians were experienced, and were responsible for priority setting at their centres. The classifications were first performed independently by the 42 clinicians (i.e., individual rating), and then evaluated utilizing team consensus within each CMHC (i.e., team rating). Interrater reliability was estimated using intraclass correlation coefficients (ICCs) while the reliability of rating across raters and units (generalizability) were estimated using generalizability analysis.

Results
The ICCs (2.1 single measure, absolute agreement) varied between 0.40 and 0.51 using individual ratings and between 0.39 and 0.58 using team ratings. Our findings suggest a fair (low) degree of interrater reliability, and no improvement of team ratings was observed when compared to individual ratings. The generalizability analysis, for one rater within each unit, yields a generalizability coefficient of 0.50 and a dependability coefficient of 0.53 (D study). These findings confirm that the reliability of ratings across raters and across units is low. Finally, the degree of inconsistency, for an average measurement, appears to be higher within units than between units (G study).

Conclusion
The low interrater reliability and generalizability found in our study suggests that horizontal equity to mental health services is not ensured with respect to priority. Priority -setting in teams provides no significant improvement compared to individual rating, and the additional use of these resources may be questionable. Improved guidelines, tutorials, training and calibration of clinicians may be utilized to improve the reliability of priority-setting.