Mechanical properties of nanosprings

Nanostructures (nanotubes, nanowires, etc.) have been the object of intense theoretical and experimental investigations in recent years. Among these structures, helical nanosprings or nanocoils have attracted particular interest due to their special mechanical properties. In this work, we investigated structural properties of nanosprings in the Kirchhoff rod model. We derived expressions that can be used experimentally to obtain nanospring Young's modulus and Poisson's ratio values. Our results also might explain why the presence of catalytic particles is so important in nanostructure growth.921

Identification of a cytokine network sustaining neutrophil and Th17 activation in untreated early rheumatoid arthritis

© 2010 Cascão et al.; licensee BioMed Central Ltd. This is an open access article distributed under the terms of the Creative Commons Attribution License (http://creativecommons.org/licenses/by/2.0), which permits unrestricted use, distribution, and reproduction in any medium, provided the original work is properly cited.Introduction: Rheumatoid arthritis (RA) is a chronic inflammatory autoimmune disease characterized by sustained synovitis. Recently, several studies have proposed neutrophils and Th17 cells as key players in the onset and perpetuation of this disease. The main goal of this work was to determine whether cytokines driving neutrophil and Th17 activation are dysregulated in very early rheumatoid arthritis patients with less than 6 weeks of disease duration and before treatment (VERA). Methods: Cytokines related to neutrophil and Th17 activation were quantified in the serum of VERA and established RA patients and compared with other very early arthritis (VEA) and healthy controls. Synovial fluid (SF) from RA and osteoarthritis (OA) patients was also analyzed. Results: VERA patients had increased serum levels of cytokines promoting Th17 polarization (IL-1b and IL-6), as well as IL-8 and Th17-derived cytokines (IL-17A and IL-22) known to induce neutrophil-mediated inflammation. In established RA this pattern is more evident within the SF. Early treatment with methotrexate or corticosteroids led to clinical improvement but without an impact on the cytokine pattern. Conclusions: VERA patients already display increased levels of cytokines related with Th17 polarization and neutrophil recruitment and activation, a dysregulation also found in SF of established RA. 0 Thus, our data suggest that a cytokine-milieu favoring Th17 and neutrophil activity is an early event in RA pathogenesis.This work was supported by a grant from Sociedade Portuguesa de Reumatologia/Schering-Plough 2005. RAM and RC were funded by Fundação para a Ciência e a Tecnologia (FCT) SFRH/BD/30247/2006 and SFRH/BD/40513/2007, respectively. MMS-C was funded by Marie Curie Intra-European Fellowship PERG-2008-239422 and a EULAR Young Investigator Award

Psychosocial correlates of physical activity in school children aged 8-10 years

Background: Understanding correlates of physical activity (PA) among children in different populations may contribute to fostering active lifestyles. This study considered gender differences in relationships between biologic (body mass index, BMI), demographic (socioeconomic sport status, SES) and psychosocial correlates of PA and level of PA in Portuguese primary school children. Methods: 683 children, aged 8–10 years, from 20 different elementary schools in northern Portugal were surveyed. Weight status was classified using International Obesity Task Force (IOTF) criteria for the BMI. Family SES was estimated from school records. PA level and psychosocial correlates (attraction to PA, perceived physical competence and parental socialization) were obtained with interview and standardized questionnaires, respectively. Sex-specific hierarchical multiple regression analyses (SPSS 18.0) were conducted and included two blocks of predictor variables (biologic and demographic, and psychosocial). Results: Level of PA was significantly higher in boys than girls. Enjoyment of participation in vigorous PA was positively associated with level of PA. Perceived acceptance by peers in games and sports and parental encouragement were positively and significantly related to PA in girls. Perceived physical competence was positively and significantly related to PA in boys. Weight status and SES were not associated with PA. Conclusions: Boys and girls differed in perceived attractiveness of PA and perceived physical competence, both of which influenced level of PA. Differences in perceptions may be important aspects of motivation for PA in school children

SRC inhibition prevents P-cadherin mediated signaling and function in basal-like breast cancer cells

BACKGROUND: Basal-like breast cancer (BLBC) is a poor prognosis subgroup of triple-negative carcinomas that still lack specific target therapies and accurate biomarkers for treatment selection. P-cadherin is frequently overexpressed in these tumors, promoting cell invasion, stem cell activity and tumorigenesis by the activation of Src-Family kinase (SRC) signaling. Therefore, our aim was to evaluate if the treatment of BLBC cells with dasatinib, the FDA approved SRC inhibitor, would impact on P-cadherin induced tumor aggressive behavior. METHODS: P-cadherin and SRC expression was evaluated in a series of invasive Breast Cancer and contingency tables and chi-square tests were performed. Cell-cell adhesion measurements were performed by Atomic Force Microscopy, where frequency histograms and Gaussian curves were applied. 2D and 3D cell migration and invasion, proteases secretion and self-renew potential were evaluated in vitro. Student's t-tests were used to determine statistically significant differences. The cadherin/catenin complex interactions were evaluated by in situ proximity-ligation assay, and statistically significant results were determined by using Mann-Whitney test with a Bonferroni correction. In vivo xenograft mouse models were used to evaluate the impact of dasatinib on tumor growth and survival. ANOVA test was used to evaluate the differences in tumor size, considering a confidence interval of 95%. Survival curves were estimated by the Kaplan-Meier's method, using the log-rank test to assess significant differences for mice overall survival. RESULTS: Our data demonstrated that P-cadherin overexpression is significantly associated with SRC activation in breast cancer cells, which was also validated in a large series of primary tumor samples. SRC activity suppression with dasatinib significantly prevented the in vitro functional effects of P-cadherin overexpressing cells, as well as their in vivo tumorigenic and metastatic ability, by increasing mice overall survival. Mechanistically, SRC inhibition affects P-cadherin downstream signaling, rescues the E-cadherin/p120-catenin complex to the cell membrane, recovering cell-cell adhesion function. CONCLUSIONS: In conclusion our findings show that targeting P-cadherin/SRC signaling and functional activity may open novel therapeutic opportunities for highly aggressive and poor prognostic basal-like breast cancer.This work was funded by Laço Grant 2014, by FEDER - Fundo Europeu de Desenvolvimento Regional funds through the COMPETE 2020 - Operacional Programme for Competitiveness and Internationalisation (POCI), Portugal 2020, and by FCT - Fundação para a Ciência e a Tecnologia/ Ministério da Ciência, Tecnologia e Ensino Superior under the projects PTDC/SAU-GMG/120049/ 2010-FCOMP-01-0124-FEDER-021209, PEst-C/SAU/LA0003/2013, NORTE-01- 0145-FEDER-000029 and POCI-01-0145-FEDER-016390. FCT funded the research grants of ASR (SFRH/BPD/75705/2011), ARN (SFRH/BD/100380/2014), BS (SFRH/ BPD/104208/2014), AFV (SFRH/BPD/90303/2012), as well as JP with Programa IFCT 2013 (FCT Investigator). IPATIMUP integrates the i3S Research Unit, which is partially supported by FCT in the framework of the project “Institute for Research and Innovation in Health Sciences” (POCI-01-0145-FEDER-007274)

Spectrum of ankylosing spondylitis in Portugal. Development of BASDAI, BASFI, BASMI and mSASSS reference centile charts

The availability of population-specific normative data regarding disease severity measures is essential for patient assessment. The goals of the current study were to characterize the pattern of ankylosing spondylitis (AS) in Portuguese patients and to develop reference centile charts for BASDAI, BASFI, BASMI and mSASSS, the most widely used assessment tools in AS. AS cases were recruited from hospital outpatient clinics, with AS defined according to the modified New York criteria. Demographic and clinical data were recorded. All radiographs were evaluated by two independent experienced readers. Centile charts for BASDAI, BASFI, BASMI and mSASSS were constructed for both genders, using generalized linear models and regression models with duration of disease as independent variable. A total of 369 patients (62.3% male, mean ± (SD) age 45.4 ± 13.2 years, mean ± (SD) disease duration 11.4 ± 10.5 years, 70.7% B27-positive) were included. Family history of AS in a first-degree relative was reported in 17.6% of the cases. Regarding clinical disease pattern, at the time of assessment 42.3% had axial disease, 2.4% peripheral disease, 40.9% mixed disease and 7.1% isolated enthesopatic disease. Anterior uveitis (33.6%) was the most common extra-articular manifestation. The centile charts suggest that females reported greater disease activity and more functional impairment than males but had lower BASMI and mSASSS scores. Data collected through this study provided a demographic and clinical profile of patients with AS in Portugal. The development of centile charts constitutes a useful tool to assess the change of disease pattern over time and in response to therapeutic interventions

Using the Juvenile Arthritis Disease Activity Score based on erythrocyte sedimentation rate or C-reactive protein level: results from the Portuguese register

Our aims were to evaluate the correlation between Juvenile Arthritis Disease Activity Score 27-joint reduced count (JADAS27) with erythrocyte sedimentation rate (ESR) and JADAS27 with C-reactive protein (CRP) scores and to test the agreement of both scores on classifying each disease activity state. We also aimed at verifying the correlation of the 2 scores across juvenile idiopathic arthritis (JIA) categories and to check the correlation between JADAS27-ESR and clinical JADAS27 (JADAS27 without ESR)

Association of Body Mass Index with Juvenile Idiopathic Arthritis Disease Activity: a Portuguese and Brazilian Collaborative Analysis

Objective: To investigate the relationship between body mass index (BMI) and disease activity in patients with Juvenile Idiopathic Arthritis (JIA). Methods: Patients with JIA, aged ≤18 years, registered at the Rheumatic Diseases Portuguese Register (Reuma.pt) in Portugal and Brazil were included. Ageand sex-specific BMI percentiles were calculated based on WHO growth standard charts and categorized into underweight (P<3), normal weight (3≤P≤85), overweight (8597). Disease activity was assessed by Juvenile Arthritis Disease Activity Score (JADAS-27). Uni- and multivariable analyses were performed. Results: A total of 275 patients were included. The prevalence of underweight, normal weight, overweight and obesity was 6.9%, 67.3%, 15.3% and 10.5%, respectively. Underweight patients had significantly higher number of active joints (p<0.001), patient’s/parent’s global assessment of disease activity (PGA) (p=0.020), physician’s global assessment of disease activity (PhGA) (p<0.001), erythrocyte sedimentation rate (ESR) (p=0.032) and overall higher JADAS-27 (p<0.001), compared to patients with normal weight, overweight and obesity. In the multivariable regression, normal weight (B=-9.43, p<0.01), overweight (B=-9.30, p=0.01) and obesity (B=-9.12, p=0.01) were significantly associated with lower disease activity compared to underweight, when adjusted for age, gender, country, ethnicity, JIA category and therapies used. The diagnosis of RF- (B=3.65, p=0.006) or RF+ polyarticular JIA (B=5.29, p=0.024), the absence of DMARD therapy (B=5.54, p<0.001) and the use of oral GC (B=4.98, p=0.002) were also associated with higher JADAS-27. Conclusion: We found an independent association between underweight and higher disease activity in patients with JIA. Further studies are needed to understand the underlying mechanisms of this association.info:eu-repo/semantics/publishedVersio

6-thioguanine treatment in inflammatory bowel disease: A critical appraisal by a European 6-TG working party

Recently, the suggestion to use 6-thioguanine (6-TG) as an alternative thiopurine in patients with inflammatory bowel disease (IBD) has been discarded due to reports about possible (hepato) toxicity. During meetings arranged in Vienna and Prague in 2004, European experts applying 6-TG further on in IBD patients presented data on safety and efficacy of 6-TG. After thorough evaluation of its risk-benefit ratio, the group consented that 6-TG may still be considered as a rescue drug in stringently defined indications in IBD, albeit restricted to a clinical research setting. As a potential indication for administering 6-TG, we delineated the requirement for maintenance therapy as well as intolerance and/or resistance to aminosalicylates, azathioprine, 6-mercaptopurine, methotrexate and infliximab. Furthermore, indications are preferred in which surgery is thought to be inappropriate. The standard 6-TG dosage should not exceed 25 mg daily. Routine laboratory controls are mandatory in short intervals. Liver biopsies should be performed after 6-12 months, three years and then three-yearly accompanied by gastroduodenoscopy, to monitor for potential hepatotoxicity, including nodular regenerative hyperplasia (NRH) and veno-occlusive disease (VOD). Treatment with 6-TG must be discontinued in case of overt or histologically proven hepatotoxicity. Copyright (c) 2006 S. Karger AG, Basel

Role of Cajal Bodies and Nucleolus in the Maturation of the U1 snRNP in Arabidopsis

Background: The biogenesis of spliceosomal snRNPs takes place in both the cytoplasm where Sm core proteins are added and snRNAs are modified at the 59 and 39 termini and in the nucleus where snRNP-specific proteins associate. U1 snRNP consists of U1 snRNA, seven Sm proteins and three snRNP-specific proteins, U1-70K, U1A, and U1C. It has been shown previously that after import to the nucleus U2 and U4/U6 snRNP-specific proteins first appear in Cajal bodies (CB) and then in splicing speckles. In addition, in cells grown under normal conditions U2, U4, U5, and U6 snRNAs/snRNPs are abundant in CBs. Therefore, it has been proposed that the final assembly of these spliceosomal snRNPs takes place in this nuclear compartment. In contrast, U1 snRNA in both animal and plant cells has rarely been found in this nuclear compartment. Methodology/Principal Findings: Here, we analysed the subnuclear distribution of Arabidopsis U1 snRNP-specific proteins fused to GFP or mRFP in transiently transformed Arabidopsis protoplasts. Irrespective of the tag used, U1-70K was exclusively found in the nucleus, whereas U1A and U1C were equally distributed between the nucleus and the cytoplasm. In the nucleus all three proteins localised to CBs and nucleoli although to different extent. Interestingly, we also found that the appearance of the three proteins in nuclear speckles differ significantly. U1-70K was mostly found in speckles whereas U1A and U1C in,90 % of cells showed diffuse nucleoplasmic in combination with CBs and nucleolar localisation. Conclusions/Significance: Our data indicate that CBs and nucleolus are involved in the maturation of U1 snRNP. Difference

Role of Cajal Bodies and Nucleolus in the Maturation of the U1 snRNP in Arabidopsis

Background: The biogenesis of spliceosomal snRNPs takes place in both the cytoplasm where Sm core proteins are added and snRNAs are modified at the 59 and 39 termini and in the nucleus where snRNP-specific proteins associate. U1 snRNP consists of U1 snRNA, seven Sm proteins and three snRNP-specific proteins, U1-70K, U1A, and U1C. It has been shown previously that after import to the nucleus U2 and U4/U6 snRNP-specific proteins first appear in Cajal bodies (CB) and then in splicing speckles. In addition, in cells grown under normal conditions U2, U4, U5, and U6 snRNAs/snRNPs are abundant in CBs. Therefore, it has been proposed that the final assembly of these spliceosomal snRNPs takes place in this nuclear compartment. In contrast, U1 snRNA in both animal and plant cells has rarely been found in this nuclear compartment. Methodology/Principal Findings: Here, we analysed the subnuclear distribution of Arabidopsis U1 snRNP-specific proteins fused to GFP or mRFP in transiently transformed Arabidopsis protoplasts. Irrespective of the tag used, U1-70K was exclusively found in the nucleus, whereas U1A and U1C were equally distributed between the nucleus and the cytoplasm. In the nucleus all three proteins localised to CBs and nucleoli although to different extent. Interestingly, we also found that the appearance of the three proteins in nuclear speckles differ significantly. U1-70K was mostly found in speckles whereas U1A and U1C in,90 % of cells showed diffuse nucleoplasmic in combination with CBs and nucleolar localisation. Conclusions/Significance: Our data indicate that CBs and nucleolus are involved in the maturation of U1 snRNP. Difference