Molecular survey of CRL618

We present the complete data set, model and line identification of a survey of the emission from the C-rich protoplanetary nebula CRL 618 performed with the IRAM-30m telescope in the following frequency ranges: 80.25-115.75 GHz, 131.25-179.25 GHz, and 204.25-275.250 GHz. A selection of lines from different species has been used in previous works to derive the structure of the source, its physical conditions and the chemical abundances in the different gas regions. In this work, we have used this information to run a global simulation of the spectrum in order to check the consistency of the model and to ease the task of line identification. The total number of lines that have a correspondence in both data and model is ~3100, although quite often in this object many lines blend into complex features so that the model, that takes into account line blending, is a key tool at this stage of the analysis. Of all the lines that we have been able to label, ~55% of them belong to the different forms of HC3N, and ~18% to those of HC5N. The density of remaining unidentified features above the 3sigma limit is only one per ~2.1 GHz (74 features), which is unprecedented in the analysis of this type of large millimeter-wave line surveys.Comment: Accepted in ApJ (November 2006). Figures bitmapped to lower resolution. The complete set of tables and figures will be published only electronically (ApJ online

Acerca de uma leitura geopolítica das relações entre Portugal e o Atlântico

O artigo pretende traçar uma breve perspectiva geopolítica da relação entre Portugal e o oceano Atlântico. Essa relação, embora sempre presente e importante, variou ao longo da nossa histó- ria. O autor, depois de tentar sumariamente caracterizar essas variações, analisa simplificadamente aquela relação no actual contexto do sistema global das relações internacionais. Dessa análise retira argumentos para afirmar que na ligação com o Atlântico poderão de novo ser encontradas as soluções mais adequadas para os nossos actuais problemas do desenvolvimento e da afirmação internacional, através da possível e desejável futura assumpção por Portugal de um papel de entreposto de importantes fluxos nas relações transatlânticas, em que as luso-brasileiras e as com a CPLP deverão desempenhar um papel centra

Impact of kinesin Eg5 inhibition by 3,4-dihydropyrimidin-2(1H)-one derivatives on various breast cancer cell features

Background Breast cancer is a complex heterogeneous disease and is one of the leading causes of death among women. In addressing the need for treatments of this life-threatening illness, we studied 3,4-dihydropyrimidin-2(1H)-one (or thione) derivatives (DHPMs), a class of inhibitor molecules of the Eg5 motor spindle protein that shows pronounced antitumor activity against several cancer cell lines. Methods An in vitro screening was performed for identification of DHPMs with potent antitumor effects on MCF-7 and MDA-MB-231 cells and the selected DHPMs were evaluated for their inhibitory activity on Eg5 both in silico, using Molecular dynamics, and in vitro Eg5 inhibition assays. Analysis of cell death induction, proliferation, cell cycle and cancer stem cells (CSC) profile were performed by flow cytometry to assess the influence of the selected DPHMs on these important tumor features. Finally, the effects of DHPM treatment on tube formation were evaluated in vitro using HUVEC cells, and in vivo using a model on chorioallantoic membrane (CAM) of fertilized eggs. Results We identified five DHPMs with pronounced inhibitory activity on Eg5 motor protein interfering with the proper mitotic spindle assembly during cell division. These compounds impair the correct conclusion of cell cycle of the breast cancer cells and showed to be selective for tumor cells. Moreover, DHPMs modulate the CD44[superscript +]/CD24[superscript −] phenotype leading to a decrease in the CSC population in MDA-MB-231 cells, an important effect since CSC are resistant to many conventional cancer therapies and play a pivotal role in tumor initiation and maintenance. This observation was confirmed by the results which demonstrated that DHPM treated cells had impaired proliferation and were unable to sustain angiogenesis events. Finally, the DHMP treated cells were induced to apoptosis, which is one of the most pursued goals in drug development. Conclusions The results of our study strongly suggest that DHPMs inhibit important tumorigenic features of breast cancer cells leading them to death by apoptosis. These findings firmly point to DHPM molecular architecture as a promising alternative against breast cancer

Comparison of Self-Reported Sleep Duration With Actigraphy: Results From the Hispanic Community Health Study/Study of Latinos Sueño Ancillary Study

Most studies of sleep and health outcomes rely on self-reported sleep duration, although correlation with objective measures is poor. In this study, we defined sociodemographic and sleep characteristics associated with misreporting and assessed whether accounting for these factors better explains variation in objective sleep duration among 2,086 participants in the Hispanic Community Health Study/Study of Latinos who completed more than 5 nights of wrist actigraphy and reported habitual bed/wake times from 2010 to 2013. Using linear regression, we examined self-report as a predictor of actigraphy-assessed sleep duration. Mean amount of time spent asleep was 7.85 (standard deviation, 1.12) hours by self-report and 6.74 (standard deviation, 1.02) hours by actigraphy; correlation between them was 0.43. For each additional hour of self-reported sleep, actigraphy time spent asleep increased by 20 minutes (95% confidence interval: 19, 22). Correlations between self-reported and actigraphy-assessed time spent asleep were lower with male sex, younger age, sleep efficiency <85%, and night-to-night variability in sleep duration ≥1.5 hours. Adding sociodemographic and sleep factors to self-reports increased the proportion of variance explained in actigraphy-assessed sleep slightly (18%–32%). In this large validation study including Hispanics/Latinos, we demonstrated a moderate correlation between self-reported and actigraphy-assessed time spent asleep. The performance of self-reports varied by demographic and sleep measures but not by Hispanic subgroup

Factors associated with severe dry eye in primary Sjögren´s syndrome diagnosed patients

Introduction Primary Sjögren?s syndrome (pSS) is an autoimmune disease, characterized by lymphocytic infiltration of exocrine glands and other organs, resulting in dry eye, dry mouth and extraglandular systemic findings. Objective To explore the association of severe or very severe dry eye with extraocular involvement in patients diagnosed with primary Sjögren?s syndrome. Methods SJOGRENSER registry is a multicenter cross-sectional study of pSS patients. For the construction of our main variable, severe/very severe dry eye, we used those variables that represented a degree 3?4 of severity according to the 2007 Dry Eye Workshop classification. First, bivariate logistic regression models were used to identify the effect of each independent variable on severe/very severe dry eye. Secondly, multivariate analysis using regression model was used to establish the independent effect of patient characteristics. Results Four hundred and thirty-seven patients were included in SJOGRENSER registry; 94% of the patients complained of dry eye and 16% developed corneal ulcer. Schirmer?s test was pathological in 92% of the patients; 378 patients presented severe/very severe dry eye. Inflammatory articular involvement was significantly more frequent in patients with severe/very severe dry eye than in those without severe/very severe dry eye (82.5 vs 69.5%, p = 0,028). Inflammatory joint involvement was associated with severe/very severe dry eye in the multivariate analysis, OR 2.079 (95% CI 1.096?3.941). Conclusion Severe or very severe dry eye is associated with the presence of inflammatory joint involvement in patients with pSS. These results suggest that a directed anamnesis including systemic comorbidities, such as the presence of inflammatory joint involvement or dry mouth in patients with dry eye, would be useful to suspect a pSS

Reconstruction of Past Environment and Climate Using Wetland Sediment Records from the Sierra Nevada

Understanding the effects of climate change and human activities on fragile mountain ecosystems is necessary to successfully managing these environments under future climate scenarios (e.g., global warming, enhanced aridity). This can be done through the study of paleoecological records, which can provide long paleoenvironmental databases containing information on how ecosystems reacted to climate change and human disturbances before the historical record. These studies can be particularly interesting when focusing on especially warm and/or dry past climatic phases. Biotic (pollen, charcoal) and abiotic (physical, geochemistry) analyses from wetland sediment records from the Sierra Nevada, southern Spain record changes in vegetation, fire history and lake sedimentation since ~11,700 years (cal yr BP). This multiproxy paleoecological study indicates that maxima in temperature and humidity occurred in the area in the Early and Middle Holocene, with a peak in precipitation between ~10,500 and 7000 cal yr BP. This is deduced by maxima in water runoff, the highest abundance of tree species and algae and high total organic carbon values recorded in the alpine wetland’s sedimentary records of the Sierra Nevada during that time period. In the last 7000 cal yr BP, and especially after a transition period between ~7000 and 5000 cal yr BP, a progressive aridification process took place, indicated by the decrease in tree species and the increase in xerophytic herbs in this region and a reduction in water runoff evidenced by the decrease in detritic input in the wetland sedimentary records. An increasing trend in Saharan dust deposition in the Sierra Nevada wetlands is also recorded through inorganic geochemical proxies, probably due to a coetaneous loss of vegetation cover in North Africa. The process of progressive aridification during the Middle and Late Holocene was interrupted by millennial-scale climatic oscillations and several periods of relative humid/droughty conditions and warm/cold periods have been identified in different temperature and/or precipitation proxies. Enhanced human impact has been observed in the Sierra Nevada in the last ~3000 cal yr BP through the increase in fires, grazing, cultivation, atmospheric pollution as well as reforestation by Pinus and the massive cultivation of Olea at lower altitudes.This study was supported by projects CGL2013-47038-R and CGL2017-85415-R funded by Ministerio de Economía y Competitividad of Spain and Fondo Europeo de Desarrollo Regional FEDER; Séneca Project 20788/PI/18; Junta de Andalucía I+D+i Junta de Andalucía 2020 Retos P-20-00059, FEDER Project B-RNM-144-UGR18, UGR-FEDER B-RNM-144-UGR18 Proyectos I + D + i del Programa Operativo FEDER 2018 and the research group RNM-190 (Junta de Andalucía). M.J.R.R. acknowledges the postdoctoral funding provided by the European Commission/H2020 (ERC-2017-ADG, project number 788616). J.C. acknowledges the postdoctoral funding provided by the Academy of Finland (project number 316702). A.G.-A. acknowledges the Ramón y Cajal fellowship RYC-2015-18966 provided by the Ministerio de Economía y Competitividad of the Spanish Government. M.R.G. acknowledges funding by the Juan de la Cierva-Incorporación program in the University of Granada (IJCI-2017-33755) from Secretaría de Estado de I+D+i, Spain. RSA acknowledges several travel grants from Northern Arizona University to support this work

Profibrotic role of inducible heat shock protein 90α isoform in systemic sclerosis

Systemic sclerosis (SSc) is an autoimmune disease that affects skin and multiple internal organs. TGF-β, a central trigger of cutaneous fibrosis, activates fibroblasts with the involvement of the stress-inducible chaperone heat shock protein 90 isoform α (Hsp90α). Available evidence supports overexpression and secretion of Hsp90α as a feature in profibrotic pathological conditions. The aim of this work is to investigate the expression and function of Hsp90α in experimental models of skin fibrosis such as human fibroblasts, C57BL/6 mice, and in human SSc. For this purpose, we generated a new experimental model based on doxorubicin administration with improved characteristics with respect to the bleomycin model. We visualized disease progression in vivo by fluorescence imaging. In this work, we obtained Hsp90α mRNA overexpression in human skin fibroblasts, in bleomycin- and doxorubicin-induced mouse fibrotic skin, and in lungs of bleomycin- and doxorubicin-treated mice. Hsp90α-deficient mice showed significantly decreased skin thickness compared with wild-type mice in both animal models. In SSc patients, serum Hsp90α levels were increased in patients with lung involvement and in patients with the diffuse form of SSc (dSSc) compared with patients with the limited form of SSc. The serum Hsp90α levels of patients dSSc were correlated with the Rodnan score and the forced vital capacity variable. These results provide new supportive evidence of the contribution of the Hsp90α isoform in the development of skin fibrosis. In SSc, these results indicated that higher serum levels were associated with dSSc and lung fibrosis.This work was supported by Spanish Ministerio de Economía, Industria y Competitividad, Gobierno de España Grant RTI2018-095214-B-I00, as well as by the Instituto de Formación e Investigación Marqués de Valdecilla IDIVAL (InnVal 17/22; InnVal 20/34), 2020UCI22-PUB-0003 Gobierno de Cantabria (to A.V.V.), SAF2016-75195-R (to J.M.), SAF2017-82905-R (to R.M.), and (NextVal 18/14) to A.P

Differential body composition effects of protease inhibitors recommended for initial treatment of HIV infection: A randomized clinical trial

This article has been accepted for publication in Clinical Infectious Diseases ©2014 The Authors .Published by Oxford University Press on Clinical Infectious Disease 60.5. DOI: 10.1093/cid/ciu898Background. It is unclear whether metabolic or body composition effects may differ between protease inhibitor-based regimens recommended for initial treatment of HIV infection. Methods. ATADAR is a phase IV, open-label, multicenter randomized clinical trial. Stable antiretroviral-naive HIV-infected adults were randomly assigned to atazanavir/ritonavir 300/100 mg or darunavir/ritonavir 800/100 mg in combination with tenofovir/emtricitabine daily. Pre-defined end-points were treatment or virological failure, drug discontinuation due to adverse effects, and laboratory and body composition changes at 96 weeks. Results. At 96 weeks, 56 (62%) atazanavir/ritonavir and 62 (71%) darunavir/ritonavir patients remained free of treatment failure (estimated difference 8.2%; 95%CI -0.6 to 21.6); and 71 (79%) atazanavir/ritonavir and 75 (85%) darunavir/ritonavir patients remained free of virological failure (estimated difference 6.3%; 95%CI -0.5 to 17.6). Seven vs. five patients discontinued atazanavir/ritonavir or darunavir/ritonavir due to adverse effects. Total and HDL cholesterol similarly increased in both arms, but triglycerides increased more in atazanavir/ritonavir arm. At 96 weeks, body fat (estimated difference 2862.2 gr; 95%CI 726.7 to 4997.7; P=0.0090), limb fat (estimated difference 1403.3 gr; 95%CI 388.4 to 2418.2; P=0.0071), and subcutaneous abdominal adipose tissue (estimated difference 28.4 cm2; 95%CI 1.9 to 55.0; P=0.0362) increased more in atazanavir/ritonavir than in darunavir/ritonavir arm. Body fat changes in atazanavir/ritonavir arm were associated with higher insulin resistance. Conclusions. We found no major differences between atazanavir/ritonavir and darunavir/ritonavir in efficacy, clinically-relevant side effects, or plasma cholesterol fractions. However, atazanavir/ritonavir led to higher triglycerides and total and subcutaneous fat than darunavir/ritonavir and fat gains with atazanavir/ritonavir were associated with insulin resistanceThis is an Investigator Sponsored Research study. It was supported in part by research grants from Bristol‐Myers Squibb and Janssen‐Cilag; Instituto de Salud Carlos III (PI12/01217) and Red Temática Cooperativa de Investigación en SIDA G03/173 (RIS‐EST11), Ministerio de Ciencia e Innovación, Spain. (Registration number: NCT01274780; registry name: ATADAR; EUDRACT; 2010‐021002‐38)

Allelic Variation of MYB10 Is the Major Force Controlling Natural Variation in Skin and Flesh Color in Strawberry (Fragaria spp.) Fruit

Independent mutations in the transcription factor MYB10 cause most of the anthocyanin variation observed in diploid woodland strawberry (Fragaria vesca) and octoploid cultivated strawberry (Fragaria x ananassa). The fruits of diploid and octoploid strawberry (Fragaria spp) show substantial natural variation in color due to distinct anthocyanin accumulation and distribution patterns. Anthocyanin biosynthesis is controlled by a clade of R2R3 MYB transcription factors, among which MYB10 is the main activator in strawberry fruit. Here, we show that mutations in MYB10 cause most of the variation in anthocyanin accumulation and distribution observed in diploid woodland strawberry (F. vesca) and octoploid cultivated strawberry (F. xananassa). Using a mapping-by-sequencing approach, we identified a gypsy-transposon in MYB10 that truncates the protein and knocks out anthocyanin biosynthesis in a white-fruited F. vesca ecotype. Two additional loss-of-function mutations in MYB10 were identified among geographically diverse white-fruited F. vesca ecotypes. Genetic and transcriptomic analyses of octoploid Fragaria spp revealed that FaMYB10-2, one of three MYB10 homoeologs identified, regulates anthocyanin biosynthesis in developing fruit. Furthermore, independent mutations in MYB10-2 are the underlying cause of natural variation in fruit skin and flesh color in octoploid strawberry. We identified a CACTA-like transposon (FaEnSpm-2) insertion in the MYB10-2 promoter of red-fleshed accessions that was associated with enhanced expression. Our findings suggest that cis-regulatory elements in FaEnSpm-2 are responsible for enhanced MYB10-2 expression and anthocyanin biosynthesis in strawberry fruit flesh.Peer reviewe