Miracle-dz/UniFAR-FTUs huggingface dataset:
Direct Interaction of Rnd1 with FRS2β Regulates Rnd1-induced Down-regulation of RhoA Activity and Is Involved in Fibroblast Growth Factor-induced Neurite Outgrowth in PC12 Cells*

The Rho family of small GTPases has been implicated in the reorganization of the actin cytoskeleton and subsequent morphological changes in various cells. Rnd1, a member of this family, has a low intrinsic GTPase activity and exerts antagonistic effects on RhoA signaling. However, how the activity of Rnd1 is regulated has not yet been elucidated. Here we have demonstrated that Rnd1 directly associates with FRS2α and FRS2β, which are docking proteins of fibroblast growth factor (FGF) receptors and play important roles in the intracellular signals induced by FGFs. The interaction of FRS2β with Rnd1 suppresses the inhibitory effect of Rnd1 on RhoA. Rnd1 binds to the COOH-terminal region of FRS2β including tyrosine residues essential for the interaction with Shp2. When FGF receptor 1 is activated, it phosphorylates FRS2β, recruits Shp2, and releases Rnd1 from FRS2β. The liberated Rnd1 then inhibits RhoA activity. Furthermore, knockdown of Rnd1 by Rnd1-specific short interfering RNAs suppress the FGF-induced neurite outgrowth in PC12 cells. These results suggest that the activity of Rnd1 is regulated by FGF receptor through FRS2β and that Rnd1 plays an important role in the FGF signaling during neurite outgrowth.
A Novel Calcium Signaling Pathway Targets the c-fosIntragenic Transcriptional Pausing Site*

In many cell types, increased intracellular calcium gives rise to a robust induction of c-fos gene expression. Here we show that in mouse Ltk− fibroblasts, calcium ionophore acts in synergy with either cAMP or PMA to strongly induce the endogenous c-fos gene. Run-on analysis shows that this corresponds to a substantial increase in active polymerases on downstream gene sequences, i.e. relief of an elongation block by calcium. Correspondingly a chimeric gene, in which the human metallothionein promoter is fused to the fos gene, is strongly induced by ionophore alone, unlike a c-fospromoter/β-globin coding unit chimeric construct. Internal deletions in the hMT-fos reporter localize the intragenic calcium regulatory element to the 5′ portion of intron 1, thereby confirming and extending previous in vitro mapping data. Ionophore induced cAMP response element-binding protein phosphorylation on Ser133without affecting the extracellular signal-regulated kinase cascade. Surprisingly, induction involved neither CaM-Ks nor calcineurin, while the calmodulin antagonist W7 activated c-fos transcription on its own. These data suggest that a novel calcium signaling pathway mediates intragenic regulation of c-fos expression via suppression of a transcriptional pause site.
Why do breast cancer patients report late or abscond during treatment in ghana? A pilot study.

OBJECTIVES To determine the causes of delayed presentation in breast cancer patients at Korle Bu Teaching Hospital (KBTH), and reasons for patients absconding before and during treatment. DESIGN Questionnaire survey. SETTING Out patient departments and surgical wards of KBTH. PARTICIPANTS Women newly diagnosed with breast cancer and breast cancer patients who previously absconded and were returning for treatment. RESULTS Sixty six newly-diagnosed patients aged between 20 and 84 (mean 44.8, median 43) years and 35 previous absconders aged 20 to 74 (mean 44.5, median 44) years were interviewed. The causes of delayed presentation were: previous medical consultations 26(29.4%), ignorance 19(28.8%), fear of mastectomy 16(24.2%), herbal treatment 13(19.7%), prayer/prayer camps 13(19.7%) and financial incapability 12(18.2%). Fear of mastectomy 20(57.1%), herbal treatment 13(37.1%), financial incapability 11(31.4%) and prayers/prayer camps 10(28.6%) which were prominent causes of late presentation, were the main reasons for absconding. Newly diagnosed patients had duration of symptoms one week to five years (mean 46, median 34 weeks). Those whose lumps were found by clinical breast examination in the community presented to hospital between six weeks to two years (mean 47, median 39 weeks). Married women were more likely to abscond (p=0.001). CONCLUSIONS There are similar reasons for delayed presentation and absconding among Ghanaian patients. These must be addressed in outreach programmes, and patients must be counselled at time of diagnosis. Dealing with the causes of delayed presentation appears more important than attempts to screen for breast cancer, since patients identified through community screening still present late to hospital.
U.S. Presidential Cycles and the Foreign Exchange Market

We examine the association between the foreign exchange rate of the US dollar and US presidential cycles. Results show that Republican presidencies tend to start with a strong dollar, which then depreciates over the course of the presidency. In contrast, Democratic presidencies tend to begin with a weak dollar that then appreciates. These patterns result in an apparent presidential effect in US foreign exchange rates, the direction of which depends on whether exchange rates are measured by levels or by returns.
Psychopathology and familial stress - comparison of boys with Fragile X syndrome and spinal muscular atrophy.

BACKGROUND Chronic illness and mental retardation are both associated with an increased rate of behavioural problems in children and with considerable emotional strain in families. The aim of the study was to analyse and compare the specific effects of two exemplary conditions on familial stress and coping. METHODS Forty-nine boys with Fragile X syndrome (FXS) were compared with 46 boys with Spinal Muscular Atrophy (SMA) and 32 male controls. Intelligence was measured with the RAVEN or K-ABC tests. Psychopathology was assessed with the CBCL questionnaire and a structured psychiatric interview (Kinder-DIPS), parental stress with the QRS, coping with the F-COPES and social support with the F-SOZU questionnaires. RESULTS The mean age of the FXS boys was 8.6, of the SMA boys 12.7 and of the controls 11.2 years. The mean IQ was 47 for the FXS, 112 for the SMA and 103 for the control groups. According to the CBCL, 89.8% of the FXS boys, 21.7% of the SMA and 15.7% of the controls had a total score in the borderline or clinical range. The rates were 63.3%, 34.8% and 21.9% for internalising and 67.3%, 10.9% and 18.8% for externalising behaviour, respectively. 81.6% of the FXS and 10.9% of the SMA patients had a DSM-IV or ICD-10 psychiatric diagnosis. The most common were ADHD (FXS: 36) and Separation Anxiety Disorder (SMA: 4). In total, parental stress was significantly higher in the FXS than in the SMA families (and in both compared to controls). There were no major inter-group differences regarding social support and familial coping. CONCLUSIONS Children with FXS are severely mentally retarded and have a high rate of mainly externalising disorders. Despite good coping abilities and social support, this is associated with high familial stress. The SMA boys, with an intelligence in the upper normal range, are no more deviant than their healthy controls. Parental stress is lower in the SMA families with good coping abilities. In conclusion, families with mentally retarded children are in even greater need of help than those of children with severe chronic illness/physical handicap.
Should genetic testing for BRCA1/2 be permitted for minors? Opinions of BRCA mutation carriers and their adult offspring

Although professional guidelines recommend against testing minors for adult‐onset genetic conditions, the genetic testing of minors for BRCA1/2 alterations has been debated in the literature. To better understand the opinions of BRCA mutation carriers regarding the genetic testing of minors and the cognitive and affective processes underlying these opinions, we interviewed BRCA mutation carriers and their adult offspring who had learned of their parent's BRCA mutation. Semi‐structured interviews were conducted with 53 parents and 22 offspring. In response to a closed‐ended question, 52% (n = 39) of participants were opposed to the testing of minors. Responses to an open‐ended question indicate that many participants (24%, n = 18) feel that testing could be permitted for some minor offspring. Psychological risks and the insufficient maturity of minors were frequent concerns of participants opposed to testing minors. The potential to impact health behaviors was frequently cited as a reason to support the genetic testing of minors. These preliminary results suggest that many BRCA mutation carriers and their adult offspring have concerns about, or are opposed to the genetic testing of minors. However, a significant minority in our study would support testing minors. Greater support for testing among offspring could indicate increasing requests for early genetic diagnosis. Further research is necessary to explore the risks and benefits of providing genetic testing to minors for adult‐onset hereditary cancer syndromes in order to inform clinical practice and public policy and to ensure optimal psychosocial and medical outcomes for all members in families at risk for genetically determined disease. © 2008 Wiley‐Liss, Inc.
Prevalence of Fusobacterium necrophorum in Children Presenting with Pharyngitis

ABSTRACT Fusobacterium necrophorum, an obligate anaerobic bacterium, was recently reported to be an important cause of bacterial pharyngitis with a prevalence as high as that of group A Streptococcus (GAS) in adolescents and young adults. Importantly, F. necrophorum is the primary causative agent of the life-threatening Lemierre's syndrome, and screening of pharyngeal samples may be warranted for its early detection and prevention. The aim of this study was to determine the prevalences of F. necrophorum and groups A and C/G streptococci as agents of bacterial pharyngitis in children. Pharyngeal samples (n = 300) were collected from pediatric patients presenting to the emergency department with signs and symptoms of pharyngitis. Overall, 10 (3.3%), 79 (26.3%), and 4 (1.3%) patients were PCR positive for F. necrophorum, GAS, and group C/G streptococci, respectively. The prevalence of F. necrophorum was significantly higher in patients between the ages of 14 and 20 years at 13.5% than in patients aged 14 years and younger (1.9%, P < 0.001). All positive patients presented with signs and symptoms similar to GAS pharyngitis. Our data demonstrated a potential role for F. necrophorum as a pathogen of pharyngitis among young adults, but suggests that the prevalence of F. necrophorum is low in preadolescent patients.
Interleukin‐1 expression in inflammatory myopathies: evidence of marked immunoreactivity in sarcoid granulomas and muscle fibres showing ischaemic and regenerative changes

The most frequent autoimmune adult inflammatory myopathies are dermatomyositis, polymyositis, inclusion body myositis, and sarcoid myopathy. Interleukin‐1 (IL‐1) is a pleiotropic molecule, implicated in the inflammatory process, but also in tissue protection and remodelling. We evaluated the immunocytochemical expression of IL‐1α and β in frozen muscle biopsy specimens from patients with dermatomyositis (15 cases), polymyositis (five cases), inclusion body myositis (five cases) and sarcoid myopathy (five cases). Positive immunoreactivities, were observed in both inflammatory cells and muscle fibres. Specificity of the immunostaining was assessed by Western blot experiments. IL‐1 positive inflammatory cells were rare in polymyositis and inclusion body myositis, moderately abundant in dermatomyositis, and prominent in sarcoid myopathy granulomas. In sarcoid myopathy, 24.6±4.1% inflammatory cells were IL‐1α‐positive and 45.2±2.6% were IL‐1β‐positive. IL‐1 positive muscle fibres were mainly observed in dermatomyositis, usually remote from inflammatory infiltrates. Positive immunostaining for IL‐1 was observed in fibres showing ischaemic punched‐out vacuoles, that correspond to areas of myosinolysis, in atrophic perifascicular fibres, and in fibres located within healing microinfarcts. All NCAM‐positive regenerating fibres were IL‐1 positive. We conclude that: (i) IL‐1 is expressed in granulomas of sarcoid myopathy, which is in keeping with the role ascribed to IL‐1 in the formation of granulomas; (ii) IL‐1 is expressed by muscle fibres undergoing ischaemic damage; and (iii) IL‐1 expression by muscle fibres is associated with myofibrillar protein breakdown and regeneration.
Higher urine heat shock protein 70/creatinine ratio in type 1 diabetes mellitus

Abstract Insidious progressive renal damage caused by type 1 diabetes mellitus (T1DM) begins in childhood before it becomes manifest in adult ages. Heat shock proteins (HSPs) regulate the cell response to any hazardous factors to prevent cell structure. The aim of the study is to determine whether urine levels of HSPs increase in diabetic children with time and indicate a progressive renal injury in T1DM. Thirty-three patients with T1DM and 24 healthy children were enrolled in the study. Renal function was normal in all patients. Urine levels of HSP27, HSP40, HSP60, HSP70, and HSP90 were measured by enzyme-linked immunosorbent assay at two consecutive years (2012 and 2013). The results were evaluated as urine HSP/creatinine ratios (uHSP/Cr). Mean urine HSP27/Cr, HSP40/Cr, HSP60/Cr, HSP70/Cr, HSP90/Cr in patient group were significantly higher than in controls in 2012 (uHSP27/Cr 460.12 ± 217.64 versus 270.02 ± 136.83 pg/mgCr; uHSP40/Cr 180.89 ± 118.59 versus 99.44 ± 62.49 pg/mgCr; uHSP60/Cr 114.40 ± 64.91 versus 70.50 ± 43.70 pg/mgCr; uHSP70/Cr 41.17 ± 28.42 versus 16.47 ± 7.32 pg/mgCr; uHSP90/Cr 175.64 ± 102.22 versus 107.61 ± 75.85 pg/mgCr) (p < 0.05). In 2013, uHSP70/Cr level increased significantly (51.08 ± 27.72 pg/mgCr; p = 0.001), whereas uHSP60/Cr level decreased and uHSP27/Cr, uHSP40/Cr, uHSP90/Cr levels remained stable (p > 0.05). Area under the curve (AUC) for uHSP70/Cr (0.957) was significantly higher than the others. Using a cutoff 22.59 pg/mgCr for uHSP70/Cr to predict of diabetic damage, sensitivity and specificity were 85% and 96%, respectively. Our results suggest that uHSP70/Cr increases over time and may indicate early phases of progressive kidney damage in diabetic children.
The sensitivity of hurricane frequency to ITCZ changes and radiatively forced warming in aquaplanet simulations

The response of hurricane frequency to climate changes in an aquaplanet configuration of a 50‐km resolution atmospheric general circulation model is examined. The lower boundary condition is an energetically consistent slab ocean with a prescribed cross‐equatorial ocean heat flux, which breaks the hemispheric symmetry and moves the Intertropical Convergence Zone (ITCZ) off the equator. In this idealized configuration, hurricane frequency increases in response to radiatively forced warming. The ITCZ shifts poleward when the model is warmed with fixed cross‐equatorial ocean heat flux, and it is argued that the increase in hurricane frequency results from this poleward shift. Varying the imposed cross‐equatorial ocean heat flux amplitude with fixed radiative forcing can isolate the effect of ITCZ shifts. If an increase in radiative forcing is accompanied by a reduction in the ocean heat flux amplitude such that the position of the ITCZ is unchanged, the simulated hurricane frequency decreases under warmed conditions.
Mining of outlier temporal patterns

Outlier temporal pattern mining problem is the study and discovery of abnormal, invalid, anomalous temporal patterns in a given temporal database. In this paper, we address the approach for mining of outlier temporal patterns with respect to a given threshold and reference. To verify if the given pattern is an outlier pattern, we compute the true support of temporal pattern and then obtain the distance between this pattern and reference temporal pattern using a novel measure. If the threshold distance computed using the proposed measure exceeds the minimum threshold limit, the pattern is treated as an outlier. Discovery and prediction of repeating temporal patterns and understanding the behavior of temporal pattern trends is quite challenging in the case of time stamped temporal datasets. At present, existing algorithms for temporal pattern mining do not have methods to reveal pattern which are emerging, seasonal and diminishing. Determining similar temporal patterns and unearthing eccentric patterns require an efficient dissimilarity measure. This research addresses the similarity measure for revealing outlier temporal patterns.
Behavior of Caveolae and Caveolin-3 During the Development of Myocyte Hypertrophy

Recent studies have indicated that caveolae are enriched in a variety of signaling molecules, some of which are associated with cardiomyocyte hypertrophy. Caveolin-3, a major constituent of cardiac caveolae, has been suggested to interact with several signaling molecules. We investigated the morphologic changes of caveolae and caveolin-3 expression in hypertrophied cardiomyocytes induced by an α1-adrenergic agonist. Cultured rat neonatal cardiomyocytes were used for the experiments. Phenylephrine induced cellular hypertrophy associated with an increase of the number of caveolae and an up-regulation of caveolin-3. Although PMA increased the number of caveolae and the caveolin-3 expression, the extent of these up-regulations was less than that by phenylephrine. Moreover, ionomycin increased the number of caveolae and up-regulated caveolin-3 as much as phenylephrine. Phenylephrine-induced up-regulations of caveolae and caveolin-3 expression were inhibited by BAPTA, suggesting that the intracellular Ca2+ is involved in those regulations. Inhibitors of calcineurin and Ca2+/calmodulin-dependent kinase II attenuated the phenylephrine-induced up-regulation of caveolin-3. In pressure-overloaded rat hearts, caveolin-3 protein levels were increased compared with sham-operated rats. In conclusion, the number of caveolae and the expression of caveolin-3 were up-regulated in rat hypertrophied cardiomyocytes, possibly via the alterations of intracellular Ca2+ and protein kinase C.
HLA-B27 Correlates with the Intracellular Elimination, Replication, and Trafficking of Salmonella Enteritidis Collected from Reactive Arthritis Patients

Background The aim of this study was to explore the correlation between HLA-B27 and the intracellular elimination, replication, and trafficking of Salmonella enteritidis (S. enteritidis) collected from patients with reactive arthritis. Material/Methods Confocal microscopy, flow cytometry, and sandwich enzyme-linked immunosorbent assay (ELISA) were employed in this study to evaluate the localization of proteins of interest, to assess the intracellular trafficking of S. enteritidis, and to measure the production of cytokines of interest. Results HLA-B27 was negatively associated with intracellular S. enteritidis elimination in healthy human monocytes/macrophages. In S. enteritidis infected monocytes/macrophages, HLA-27B was also negatively correlated with bacteria elimination but positively related to bacteria replication. S. enteritidis did not co-localize with NRAMP1 and LAMP1/2 in HLA-B27 cells. S. enteritidis did not co-exist with transferrin or dextran within HLA-B27 and A2 cells. Conclusions HLA-B27 is closely associated with the intracellular elimination and replication of S. enteritidis. Replicated bacteria in HLA-B27 monocytic cells were located within unique vacuoles rather than disturbing host endocytosis.
On modeling the variability of bedform dimensions

Bedforms are irregular features that cannot easily be described by mean values. The variations in the geometric dimensions affect the bed roughness, and they are important in the modeling of vertical sorting and in modeling the thickness of cross-strata sets. The authors analyze the variability of bedform dimensions for three sets of flume experiments, considering PDFs of bedform height, trough elevation and crest elevation divided by its mean value. It appears that the dimensionless standard deviation of the bedform height is within a narrow range for nearly all experiments. This appears to be valid for the trough elevation and crest elevation, as well. For some modeling purposes, it seems sufficient to assume that the standard deviation is a constant, so that the variation in bedform dimension can be modeled by only predicting the mean bedform dimension.
Effets de bétons bio-actifs sur la colonisation marine en environnement méditerranéen

Les phenomenes de colonisation de substrats en beton sont des elements d’avenir pour l’amelioration des fonctions ecologiques d’ouvrages maritimes eco-concus. C’est dans cet objectif que L’Ecole des mines d’Ales et l’Universite Montpellier III-CEFE UMR 5175 ont fabrique et immerge quatre betons de formulations differentes durant 56 jours. La colonisation par des organismes vivants sur un beton de reference, un beton a base de granulats biogenes et de deux bio-betons contenant des activateurs organique ou mineral a ete observee experimentalement au moyen de prises regulieres de photographies de la surface des eprouvettes puis par traitement d’images. Certaines formulations semblent ameliorer la colonisation biologique, notamment celles associant des bio-activateurs : developpement de biofilms, algues et petits animaux. Dans le meme temps, l’emploi de certains ajouts peut aussi influer de maniere negative et significative sur la resistance mecanique du materiau. L’effet perturbateur de parametres du milieu tels qu’une sedimentation aleatoire a egalement ete mis en lumiere. La formulation d’un eco-beton resulte d’un compromis entre des objectifs fonctionnels de resistance mecanique et de durabilite dans l’environnement et des objectifs environnementaux de colonisation par le vivant.
A putative lateral flagella of the cystic fibrosis pathogen Burkholderia dolosa regulates swimming motility and host cytokine production

Burkholderia dolosa caused an outbreak in the cystic fibrosis clinic at Boston Children’s Hospital and was associated with high mortality in these patients. This species is part of a larger complex of opportunistic pathogens known as the Burkholderia cepacia complex (Bcc). Compared to other species in the Bcc, B. dolosa is highly transmissible; thus understanding its virulence mechanisms is important for preventing future outbreaks. The genome of one of the outbreak strains, AU0158, revealed a homolog of the lafA gene encoding a putative lateral flagellin, which, in other non-Bcc species, is used for movement on solid surfaces, attachment to host cells, or movement inside host cells. Here, we analyzed the conservation of the lafA gene and protein sequences, which are distinct from those of the polar flagella, and found lafA homologs to be present in numerous β-proteobacteria but notably absent from most other Bcc species. A lafA deletion mutant in B. dolosa showed a greater swimming motility than wild-type due to an increase in the number of polar flagella, but did not appear to contribute to biofilm formation, host cell invasion, or murine lung colonization or persistence over time. However, the lafA gene was important for cytokine production in human peripheral blood mononuclear cells, suggesting it may have a role in recognition by the human immune response.