bluuebunny/crossref_metadata_2025_split huggingface dataset:
Inhibition of the Kit Ligand/c-Kit Axis Attenuates Metastasis in a Mouse Model Mimicking Local Breast Cancer Relapse after Radiotherapy
Authors: Kuonen François , Laurent Julien , Secondini Chiara , Lorusso Girieca , Stehle Jean-Christophe , Rausch Thierry , Faes-van't Hull Eveline , Bieler Grégory , Alghisi Gian-Carlo , Schwendener Reto , Andrejevic-Blant Snezana , Mirimanoff René-Olivier , Rüegg Curzio 
Published: June 2012

Abstract
Purpose: Local breast cancer relapse after breast-saving surgery and radiotherapy is associated with increased risk of distant metastasis formation. The mechanisms involved remain largely elusive. We used the well-characterized 4T1 syngeneic, orthotopic breast cancer model to identify novel mechanisms of postradiation metastasis.
Experimental Design: 4T1 cells were injected in 20 Gy preirradiated mammary tissue to mimic postradiation relapses, or in nonirradiated mammary tissue, as control, of immunocompetent BALB/c mice. Molecular, biochemical, cellular, histologic analyses, adoptive cell transfer, genetic, and pharmacologic interventions were carried out.
Results: Tumors growing in preirradiated mammary tissue had reduced angiogenesis and were more hypoxic, invasive, and metastatic to lung and lymph nodes compared with control tumors. Increased metastasis involved the mobilization of CD11b+c-Kit+Ly6GhighLy6Clow(Gr1+) myeloid cells through the HIF1-dependent expression of Kit ligand (KitL) by hypoxic tumor cells. KitL-mobilized myeloid cells homed to primary tumors and premetastatic lungs, to give rise to CD11b+c-Kit− cells. Pharmacologic inhibition of HIF1, silencing of KitL expression in tumor cells, and inhibition of c-Kit with an anti-c-Kit–blocking antibody or with a tyrosine kinase inhibitor prevented the mobilization of CD11b+c-Kit+ cells and attenuated metastasis. C-Kit inhibition was also effective in reducing mobilization of CD11b+c-Kit+ cells and inhibiting lung metastasis after irradiation of established tumors.
Conclusions: Our work defines KitL/c-Kit as a previously unidentified axis critically involved in promoting metastasis of 4T1 tumors growing in preirradiated mammary tissue. Pharmacologic inhibition of this axis represents a potential therapeutic strategy to prevent metastasis in breast cancer patients with local relapses after radiotherapy. Clin Cancer Res; 18(16); 4365–74. ©2012 AACR.
Comparison of neuropsychological functioning and emotional processing in major depression and social anxiety disorder subjects, and matched healthy controls
Authors: Bourke Cecilia , Porter Richard J , Carter Janet D , McIntosh Virginia V , Jordan Jennifer , Bell Caroline , Carter Frances , Colhoun Helen , Joyce Peter R 
Published: June 2012

Objectives: Few studies of neuropsychological function in major depression have examined emotional processing or the impact of gender. Patients have also been compared with highly selected control participants and rarely with other patient groups. The objective of this study was to compare neuropsychological function in a major depressive episode (MDE) with a group of patients with an anxiety disorder, social anxiety disorder (SAD), and healthy controls, to include measures of emotional processing and to analyse the effects of gender on neuropsychological function and emotional processing in these groups. Method: One hundred and one medication-free patients with MDE, 30 patients with SAD and 76 healthy control participants were recruited. The groups were matched for age and estimated premorbid intelligence and education. Subjects performed a battery of neuropsychological tests assessing; verbal learning and memory, visuospatial learning and memory, attention, executive function and psychomotor performance. They also performed a task measuring the accuracy of recognition of facial emotional expressions. Results: Compared with healthy participants and those with SAD, patients with MDE were significantly impaired in verbal learning and spatial working memory. The SAD group misclassified significantly more neutral expressions as angry and fewer as sad, compared with the MDE group and healthy controls, but there were no significant differences between the MDE group and healthy controls. The profile of performance was the same regardless of gender. Conclusions: The study confirms a significant impairment in neuropsychological function in a clinical sample of outpatients with MDE, which is likely to have important implications for day-to-day functioning and treatment.
Visual Representations of Children and Ritual in the Early Roman Empire
Authors: Tulloch Janet 
Published: June 2012

This paper takes the position that the best way to identify figures of children participating in scenes of early Christian ritual is through a comparison of child figures in Roman art and ritual. For the purpose of this comparison we refer to Roman scenes showing children in processions, offerings/sacrifices and banquets. Early Christian scenes of offerings which continued the representation of children but omitted the priest and musicians may have aided the identification of the scene as a gift or donation rather than a Roman sacrifice. While there is no ambiguity as to the figures in many of the early Christian baptism scenes being children, there is a long standing debate whether the child figures symbolically represent Jesus’ immersion in the Jordan river or actual baptizands. Possible similarities between Roman purification rituals by immersion in water and early Christian baptism, especially with regard to the visual representation of these rituals, remain a fruitful area for future research. Cet article propose que la meilleure façon d’identifier les images d’enfants qui participaient aux scènes d’anciens rituels chrétiens est par une comparaison des images d’enfants représentés dans l’art et le rituel romains. Aux fins de cette comparaison nous nous référons à des scènes montrant des enfants romains dans les processions, les offrandes/sacrifices et les banquets. Les anciennes scènes chrétiennes de l’offrande qui ont inclus la représentation des enfants, mais qui ne représentent ni le prêtre ni les musiciens, ont pu avoir aidé à l’identification de la scène comme un cadeau ou un don chrétien plutôt que d’un sacrifice romain. Bien qu’il n’y ait aucune ambiguïté que les images dans la plupart des scènes d’ancien baptême chrétien sont des enfants, il y a un débat de longue date de savoir si les images d’enfants représentent symboliquement l’immersion de Jésus dans le fleuve Jourdain ou bien de baptisés réels. Il est possible qu’il y ait des similarités entre les rituels de purification romain par immersion dans l’eau et l’ancien baptême chrétien, en particulier à l’égard de la représentation visuelle de ces rituels, ce qui mérite davantage de recherche.
Bowling Alone: Urban Tribes in Concrete Jungles
Authors: Murty K. Radhakrishna 
Published: June 2012

Utilising the modern social network theory, the present descriptive article has examined the art of urbanites’ ‘bowling alone’ in concrete jungles and its negative effect on their social and civic life. Mainly, such a process has resulted in the formation of ‘urban tribes’ characterized by their isolation from the mainstream social life influenced by people’s ego-centric and limited personal networks in the form of cliques with clique culture, dominated by rugged individualism, instead of developing broad social networks based on reciprocity that generate social capital with community feeling, collective consciousness and altruism. Their silent withdrawal from social intercourse has affected urbanites propensity to pitch into the common tasks that bind people together with a ‘we feeling’. The net result is, today, people in large cities have collectively turned away from the responsibilities of community building, community development and community participation in civic activities and social and public affairs. The article in this context has identified some of the factors that have contributed to this urban pathology and civic malaise and, finally, offers some possible and feasible remedies to control and contain this social malady.
Independent Evaluation
Authors: Brown Abigail B. , Klerman Jacob Alex 
Published: June 2012

Background: Maintaining the independence of contract government program evaluation presents significant contracting challenges. The ideal outcome for an agency is often both the impression of an independent evaluation and a glowing report. In this, independent evaluation is like financial statement audits: firm management wants both a public accounting firm to attest to the fairness of its financial accounts and to be allowed to account for transactions as it sees fit. In both cases, the evaluation or audit is being conducted on behalf of outsiders–the public or shareholders–but is overseen by a party with significant interests at stake in the outcome–the agency being evaluated or executive management of the firm. Method: We review the contracting strategies developed to maintain independence in auditing. We examine evidence on the effectiveness of professionalism, reputation, liability and owner oversight in constraining behavior in auditing. We then establish parallels with contracting for evaluations and apply these insights to changes that might maintain and improve evaluator independence. Conclusions and Recommendations: By analogy with the Sarbanes Oxley Act of 2002 reforms in auditing, we recommend exploring using a reformulated Technical Working Group to encourage more prompt release of more evaluation results and to help insulate evaluators from inappropriate pressure to change their results or analysis approach.
Does β2-adrenergic stimulation attenuate fluid extravasation during hypothermic cardiopulmonary bypass? An experimental study in pigs
Authors: Husby P , Brekke HK , Mongstad A , Farstad M , Haugen O , Kvalheim VL 
Published: June 2012

Objectives: Hypothermic cardiopulmonary bypass (CPB) is associated with increased fluid filtration, edema formation and, occasionally, organ dysfunction. Cold-induced reduction in endothelial barrier function may play a role. β2-adrenergic activation elevates cellular cyclic adenosine monophosphate (cAMP) which maintains endothelial barrier properties. In this study, we tested whether β-adrenergic stimulation could influence the increase in fluid extravasation observed during hypothermic CPB. Materials and methods: Fourteen pigs randomly received terbutaline infusion (T-group) (n=7) or a control infusion (C-group) (n=7). All animals were given 60 min of normothermic CPB, followed by 90 min of hypothermic CPB. Fluid input and losses, plasma volume, colloid osmotic pressures (plasma, interstitial fluid), hematocrit, serum proteins and total tissue water content were measured and the fluid extravasation rates (FER) calculated. Statistics: by SPSS. Values presented as mean ± SD. Repeated measure analysis of variance was performed and a t-test used when appropriate. Results: The commencement of normothermic CPB resulted in a 20% hemodilution, with an abrupt increase in fluid requirements during the first 10 min. FER increased from 0.18 (0.06) pre-bypass to 0.78 (0.27) ml/kg/min (T-group) (p=0.002) and from 0.16 (0.05) to 0.93 (0.26) ml/kg/min (C-group) (p<0.001) with no between-group differences. Thereafter, FER stabilized at a level of 0.32 (0.13) and 0.27 (0.14) ml/kg/min in the T-group and C-group, respectively. After the start of cooling, FER increased in the T-group to 0.55 (0.12) ml/kg/min (P=0.046) and in the C-group to 0.54 (0.13) ml/kg/min (P=0.006), with no between-group differences (P=0.738). Conclusion: In the present experimental study, we were unable to demonstrate any clinically relevant modulating effect of terbutaline on fluid extravasation during hypothermic cardiopulmonary bypass.
Coat-hanger ache in orthostatic hypotension
Authors: Khurana Ramesh K 
Published: June 2012

Background Questionnaires administered to orthostatic hypotension (OH) patients reveal frequent occurrence of coat-hanger ache (CHA), but laboratory-based precipitation of CHA during head-up tilt (HUT) has not been investigated. This study compared the frequency and clinical aspects of CHA in the same group of OH patients during daily activities versus during HUT. Methods Retrospective IRB-approved review of prospectively collected data on 22 dysautonomic patients. Heart rate response to deep breathing, Valsalva manoeuver, HUT and thermoregulatory sweat test evaluated cardiovagal, adrenergic and sudomotor functions. Occurrence and clinical features of CHA during daily activities and during HUT were recorded. Data were analysed with descriptive statistics. Results All patients demonstrated severe adrenergic (OH), cardiovagal and sudomotor impairment. Of 22 patients, 13 (59%) reported CHA within 3–5 minutes of standing or after 10 minutes to 2 hours of sitting that was relieved within 5–20 minutes of recumbency. During HUT, 4 of 13 (18%) patients developed CHA. Clinical features varied. Conclusions CHA was reported by 59% of OH patients during daily activities and by only 18% during HUT. The clinical characteristics of CHA episodes displayed inter-individual and intra-individual variability. These findings militate against direct association between OH and CHA and suggest a complex pathophysiology.
Lesion morphology at 7 Tesla MRI differentiates Susac syndrome from multiple sclerosis
Authors: Wuerfel Jens , Sinnecker Tim , Ringelstein E Bernd , Jarius Sven , Schwindt Wolfram , Niendorf Thoralf , Paul Friedemann , Kleffner Ilka , Dörr Jan 
Published: June 2012

Background: Although an orphan disease with still obscure aetiopathogenesis, Susac syndrome has to be considered as differential diagnosis in multiple sclerosis (MS), since its clinical presentation and paraclinical features including routine magnetic resonance imaging (MRI) findings partially overlap. Objective: We aimed to study a potential benefit of 7T MRI for (i) the differentiation between Susac syndrome and MS and (ii) the clarification of pathogenesis of Susac syndrome. Methods: Five patients suffering from Susac syndrome, 10 sex- and age-matched patients with relapsing–remitting MS (median Expanded Disability Status Scale (EDSS) score 1.5) and 15 matching healthy controls were investigated at 7 Tesla MRI. The protocol included T1-weighted MPRAGE, T2*-weighted FLASH, and TIRM sequences. Results: Almost all T2* FLASH lesions in patients with MS were centred by a small central vein (325 lesions; 92%) and often showed a small hypointense rim (145 lesions; 41%). In contrast, white matter lesions in Susac syndrome exhibited a perivascular setting significantly less frequently (148 lesions; 54%, p=0.002), and very rarely exhibited a hypointense rim (12 lesions; 4%, p=0.004). Furthermore, in addition to callosal atrophy, Susac patients showed cerebrospinal fluid-isointense lesions within the central part of corpus callosum that are not commonly seen in MS. Conclusion: At 7T MRI, plaques in MS patients and patients with Susac syndrome differed substantially with respect to morphology and pattern. Thus, lesion morphology at 7T (i) may serve as a marker to distinguish Susac syndrome from MS and (ii) reflects a different pathophysiological mechanism underlying Susac syndrome, for example microinfarction rather than demyelination.
Sex ratio of multiple sclerosis in the National Swedish MS Register (SMSreg)
Authors: Boström Inger , Stawiarz Leszek , Landtblom Anne-Marie 
Published: June 2012

Background: Sex ratio in multiple sclerosis has been reported from several geographical areas. The disease is more common in women. In Europe the female-to-male ratio varies from 1.1 to 3.4. A recent study from Canada has reported a significant increase, with time, in female-to-male ratio in multiple sclerosis over the last 100 years. Objective: The aim of this study was to analyse any change in sex ratio in multiple sclerosis in the Swedish population. Methods: Data from the Swedish MS Register and data from the Swedish National Statistics Office were used to estimate sex ratio by year of birth and year of onset. Results: In the analysis of sex ratio by year of birth there were 8834 patients (6271 women and 2563 men) born between 1931 and 1985. The mean women-to-men ratio was 2.62. No clear trend was noted for the women-to-men ratio by year of birth (Spearman’s rho = 0.345, p = 0.298, n = 11). The number of patients analysed by year of onset was 9098 during the time period 1946 until 2005. The mean women-to-men ratio was 2.57. No significant change in women-to-men ratio (Spearman’s rho = −0.007, p = 0.983, n = 12) with time was observed. Conclusion: There is no evidence for an increasing women-to-men ratio with time amongst Swedish multiple sclerosis patients.
The folliculin-FNIP1 pathway deleted in human Birt-Hogg-Dubé syndrome is required for murine B-cell development
Authors: Baba Masaya , Keller Jonathan R. , Sun Hong-Wei , Resch Wolfgang , Kuchen Stefan , Suh Hyung Chan , Hasumi Hisashi , Hasumi Yukiko , Kieffer-Kwon Kyong-Rim , Gonzalez Carme Gallego , Hughes Robert M. , Klein Mara E. , Oh Hyoungbin F. , Bible Paul , Southon Eileen , Tessarollo Lino , Schmidt Laura S. , Linehan W. Marston , Casellas Rafael 
Published: June 2012

Abstract
Birt-Hogg-Dubé (BHD) syndrome is an autosomal dominant disorder characterized by cutaneous fibrofolliculomas, pulmonary cysts, and kidney malignancies. Affected individuals carry germ line mutations in folliculin (FLCN), a tumor suppressor gene that becomes biallelically inactivated in kidney tumors by second-hit mutations. Similar to other factors implicated in kidney cancer, FLCN has been shown to modulate activation of mammalian target of rapamycin (mTOR). However, its precise in vivo function is largely unknown because germ line deletion of Flcn results in early embryonic lethality in animal models. Here, we describe mice deficient in the newly characterized folliculin-interacting protein 1 (Fnip1). In contrast to Flcn, Fnip1−/− mice develop normally, are not susceptible to kidney neoplasia, but display a striking pro-B cell block that is entirely independent of mTOR activity. We show that this developmental arrest results from rapid caspase-induced pre-B cell death, and that a Bcl2 transgene reconstitutes mature B-cell populations, respectively. We also demonstrate that conditional deletion of Flcn recapitulates the pro-B cell arrest of Fnip1−/− mice. Our studies thus demonstrate that the FLCN-FNIP complex deregulated in BHD syndrome is absolutely required for B-cell differentiation, and that it functions through both mTOR-dependent and independent pathways.
Analysis of C. elegans NR2E nuclear receptors defines three conserved clades and ligand-independent functions
Authors: Weber Katherine P , Alvaro Christopher G , Baer G Michael , Reinert Kristy , Cheng Genevieve , Clever Sheila , Wightman Bruce 
Published: June 2012

AbstractBackgroundThe nuclear receptors (NRs) are an important class of transcription factors that are conserved across animal phyla. Canonical NRs consist of a DNA-binding domain (DBD) and ligand-binding domain (LBD). While most animals have 20–40 NRs, nematodes of the genusCaenorhabditishave experienced a spectacular proliferation and divergence of NR genes. The LBDs of evolutionarily-conservedCaenorhabditisNRs have diverged sharply from theirDrosophilaand vertebrate orthologs, while the DBDs have been strongly conserved. The NR2E family of NRs play critical roles in development, especially in the nervous system. In this study, we explore the phylogenetics and function of the NR2E family ofCaenorhabditis elegans, using anin vivoassay to test LBD function.ResultsPhylogenetic analysis reveals that the NR2E family of NRs consists of three broadly-conserved clades of orthologous NRs. InC. elegans, these clades are defined bynhr-67, fax-1andnhr-239.The vertebrate orthologs ofnhr-67andfax-1areTlxandPNR,respectively. While thenhr-239clade includes orthologs in insects (Hr83), an echinoderm, and a hemichordate, the gene appears to have been lost from vertebrate lineages. TheC. elegansandC. briggsae nhr-239genes have an apparently-truncated and highly-diverged LBD region. An additionalC. elegansNR2E gene,nhr-111, appears to be a recently-evolved paralog offax-1;it is present inC. elegans, but notC. briggsaeor other animals with completely-sequenced genomes. Analysis of the relatively unstudiednhr-111andnhr-239genes demonstrates that they are both expressed—nhr-111very broadly andnhr-239in a small subset of neurons. Analysis of the FAX-1 LBD in anin vivoassay revealed that it is not required for at least some developmental functions.ConclusionsOur analysis supports three conserved clades of NR2E receptors, only two of which are represented in vertebrates, indicating three ancestral NR2E genes in the urbilateria. The lack of a requirement for a FAX-1 LBD suggests that the relatively high level of sequence divergence forCaenorhabditisLBDs reflects relaxed selection on the primary sequence as opposed to divergent positive selection. This observation is consistent with a model in which divergence of someCaenorhabditisLBDs is allowed, at least in part, by the absence of a ligand requirement.
Genome-wide evaluation of genetic diversity and linkage disequilibrium in winter and spring triticale (x Triticosecale Wittmack)
Authors: Alheit Katharina V , Maurer Hans Peter , Reif Jochen C , Tucker Matthew R , Hahn Volker , Weissmann Elmar A , Würschum Tobias 
Published: June 2012

Abstract

Background
Recent advances in genotyping with high-density markers nowadays enable genome-wide genomic analyses in crops. A detailed characterisation of the population structure and linkage disequilibrium (LD) is essential for the application of genomic approaches and consequently for knowledge-based breeding. In this study we used the triticale-specific DArT array to analyze population structure, genetic diversity, and LD in a worldwide set of 161 winter and spring triticale lines.

Results
The principal coordinate analysis revealed that the first principal coordinate divides the triticale population into two clusters according to their growth habit. The density distributions of the first ten principal coordinates revealed that several show a distribution indicative of population structure. In addition, we observed relatedness within growth habits which was higher among the spring types than among the winter types. The genome-wide analysis of polymorphic information content (PIC) showed that the PIC is variable among and along chromosomes and that especially the R genome of spring types possesses a reduced genetic diversity. We also found that several chromosomes showed regions of high genetic distance between the two growth habits, indicative of divergent selection. Regarding linkage disequilibrium, the A and B genomes showed a similar LD of 0.24 for closely linked markers and a decay within approximately 12 cM. LD in the R genome was lower with 0.19 and decayed within a shorter map distance of approximately 5 cM. The extent of LD was generally higher for the spring types compared to the winter types. In addition, we observed strong variability of LD along the chromosomes.

Conclusions
Our results confirm winter and spring growth habit are the major contributors to population structure in triticale, and a family structure exists in both growth types. The specific patterns of genetic diversity observed within these types, such as the low diversity on some rye chromosomes of spring habits, provide a basis for targeted broadening of the available breeding germplasm. In addition, the genome-wide analysis of the extent and the pattern of LD will assist scientists and breeders alike in the implementation and the interpretation of association mapping in triticale.