Down-regulation of thyroid transcription factor-1 gene expression in fetal lung hypoplasia is restored by glucocorticoids

8 pages, 6 figures.The thyroid transcription factor (TTF)-1 has an essential role in lung morphogenesis and development. It is involved in the transcription of surfactant proteins (SP), which are critical in respiratory function. Neonates with congenital diaphragmatic hernia die of respiratory failure caused by pulmonary hypoplasia with associated biochemical immaturity. To gain new insights into the causes of this disorder and the effect of prenatal hormonal treatment on reducing mortality in these infants, we evaluated the expression of TTF-1 as marker of lung morphogenesis and SP-B as marker of lung maturity. Using a rat model of lung immaturity, we show that TTF-1 and SP-B messenger RNA (mRNA) levels are drastically reduced in congenital lung hypoplasia. Interestingly, prenatal dexamethasone (Dex) treatment increased both TTF-1 and SP-B mRNAs over control levels when administered to rats with lung hypoplasia, but it had no effect on TTF-1 or a moderate effect on SP-B mRNA when administered to control rats. TRH alone also increases TTF-1 and SP-B mRNA levels but to a lesser extent than Dex. When administered together with Dex, TRH counteracts the induction observed with the glucocorticoid. The decrease in TTF-1 mRNA levels in lung hypoplasia is paralleled by a down-regulation of TTF-1 protein levels, as well as by a decrease in the TTF-1/DNA complex when the TTF-1-binding site of the SP-B promoter was used as a probe. Both parameters were reestablished after glucocorticoid treatment. Moreover, the regulation of TTF-1 gene expression described in this report is accompanied by the same regulation in its promoter activity, as demonstrated in transfection experiments performed in H-441 human lung-derived adenocarcinoma cells. In conclusion, our data demonstrate, for the first time, that lung hypoplasia and the associated respiratory dysfunction caused by SP-B deficiency are caused, in part, by down-regulation of TTF-1 gene expression. The observations that prenatal glucocorticoid treatment induces the expression of TTF-1 supports routine in utero glucocorticoid treatment of patients expected to have lung hypoplasia.This work was supported by Grants DGICYT (PB97–0065), CAM 08.1/0025/1997, and FIS (96/0059–01 and 98/0518) (Spain). Alejandro Losada recipient of a fellowship from the Spanish Ministerio de Educación y Cultura.Peer reviewe

Evolution of a fluvial-dominated delta during the Oligocene of the Colombian Caribbean: Sedimentological and ichnological signatures in well-cores

We would like to thank Dr. Pazos (JSAES Guest Editor) and two anonymous reviewers by constructive comments and suggestions. Thanks to the National Hydrocarbons Agency-ANH, and Ministerio de Ciencia, Tecnologia e Innovacion-Minciencias to allow the study of well-core (project Contrato RC 494-2017) . The Vicerrectoria de Inves-tigaciones y Posgrados and the Instituto de Investigaciones en Estrati-grafia-IIES of Universidad de Caldas gave economic and logistic support. The research was conducted within the "Ichnology and Palaeoenviron-ment RG" (UGR) . Financial support of Rodriguez-Tovar was provided by scientific Projects CGL 2015-66835-P and CTM 2016-75129-C3-2-R (Secretaria de Estado de I + D + I, Spain) , and B-RNM-072-UGR18 (FEDER Andalucia) , and Research Group RNM-178 (Junta de Andalucia) . Funding for open access charge: Universidad de Granada/CBUA. Thanks to Fabian Gallego for his contribution in some sedimentological discussions.Basin analysis from Colombian Caribbean is particularly important given the interest in finding hydrocarbon reservoirs, but their complex geological evolution, and the frequent lateral and vertical variation of facies difficult a conclusive characterization, highlights the need for detailed sedimentological and ichnological studies. The study succession corresponds to an interval of a well core drilled in the south of the Sinu-San Jacinto Basin (Colombian Caribbean), with 1069 ft (similar to 326 m) thick of an Oligocene siliciclastic succession, interpreted in general terms, as deposited in a deltaic system. The integrated sedimentological/ichnological analysis allows the differentiation of dominant facies, with predominant lithologies such as conglomerates, sandstones, mudrocks, bioclastic sediments, as well as coal beds. The ichnological assemblage is low in abundance and moderately diverse, composed by Conichnus, Cylindrichnus, Dactyloidites, Macaronichnus, Ophiomorpha, Phycosiphon, Skolithos, Taenidium, Teichichnus, and Thalassinoides, as well as rhizoliths. The complexity of the sedimentary system is reflected in its evolution throughout the Oligocene. A type succession with coarsening-upward trend was identified and it is repeated through the succession studied. It presents a general trend from bioclastic sediments (bioclastic conglomerates, sandstones and mudrocks) that pass into horizontal lamination and massive mudrocks occasionally bioturbated by Phycosiphon, and interbedded by mudrocks and sandstones with lenticular bedding, and the occurrence of Teichichnus. Above, bioturbated muddy sandstones with Ophiomorpha, Taenidium, Thalassinoides, and rarely Teichichnus, muddy sandstones with planar cross-lamination, and horizontal lamination sandstones with Dactyloidites, Ophiomorpha, Skolithos, and Thalassinoides are registered. Transition to carbonaceous mudrocks with Teichichnus, coal medium beds, and fine-to coarse-grained sandstones sometimes with Macaronichnus and/or Ophiomorpha is observed. Towards the top, are observed mudrocks with rhizoliths. This succession is interrupted by massive and horizontal lamination sandstones with low bioturbation index generated by the ichnological assemblage and/or by the exclusive occurrence of Ophiomorpha and/or Taenidium. Massive sandstones with erosive bases, asymmetrical ripples, and high content of organic debris are occasionally recorded. This succession reflects a progradational trend similar to those of fluvial-dominated deltaic sequences. Detailed analysis revealed that even the fluvial processes were dominant in the deltaic system; however, local tidal and wave influence is recorded. Moreover, integration of sedimentological and ichnological information allows characterizing the evolution of the different sub-environments of the deltaic system, as prodelta bay, distal delta front, proximal delta front, distributary channels, mouth bars, and lower delta plain, and this is essential for areas of economic interest.Ministerio de Ciencia, Tecnologia e Innovacion-Minciencias RC 494-2017Secretaria de Estado de I + D + I, Spain CGL 2015-66835-P- CTM 2016-75129-C3-2-RFEDER Andalucia B-RNM-072-UGR18Junta de Andalucia RNM-178Universidad de Granada/CBU

All about (nk cell-mediated) death in two acts and an unexpected encore: initiation, execution and activation of adaptive immunity

NK cells are key mediators of immune cell-mediated cytotoxicity toward infected and transformed cells, being one of the main executors of cell death in the immune system. NK cells recognize target cells through an array of inhibitory and activating receptors for endogenous or exogenous pathogen-derived ligands, which together with adhesion molecules form a structure known as immunological synapse that regulates NK cell effector functions. The main and best characterized mechanisms involved in NK cell-mediated cytotoxicity are the granule exocytosis pathway (perforin/granzymes) and the expression of death ligands. These pathways are recognized as activators of different cell death programmes on the target cells leading to their destruction. However, most studies analyzing these pathways have used pure recombinant or native proteins instead of intact NK cells and, thus, extrapolation of the results to NK cell-mediated cell death might be difficult. Specially, since the activation of granule exocytosis and/or death ligands during NK cell-mediated elimination of target cells might be influenced by the stimulus received from target cells and other microenvironment components, which might affect the cell death pathways activated on target cells. Here we will review and discuss the available experimental evidence on how NK cells kill target cells, with a special focus on the different cell death modalities that have been found to be activated during NK cell-mediated cytotoxicity; including apoptosis and more inflammatory pathways like necroptosis and pyroptosis. In light of this new evidence, we will develop the new concept of cell death induced by NK cells as a new regulatory mechanism linking innate immune response with the activation of tumour adaptive T cell responses, which might be the initiating stimulus that trigger the cancer-immunity cycle. The use of the different cell death pathways and the modulation of the tumour cell molecular machinery regulating them might affect not only tumour cell elimination by NK cells but, in addition, the generation of T cell responses against the tumour that would contribute to efficient tumour elimination and generate cancer immune memory preventing potential recurrences

Evolution of the gulf of Cadiz margin and southwest Portugal contourite depositional system : Tectonic, sedimentary and paleoceanographic implications from IODP expedition 339

Acknowledgments This research used samples and data collected through the Integrated Ocean Drilling Program (IODP). The research was partially supported through the CTM 2008-06399-C04/MAR, CTM 2012-39599-C03, CGL2011-26493, CTM2012-38248, SA263U14, IGCP-619, INQUA 1204 and FWF P25831-N29 Projects. Some data were collected with 94-1090-C03-03 (FADO) and MAR-98-0209 (TASYO) Projects. Research was conducted in the framework of the Continental Margins Research Group of the Royal Holloway University of London, People and the Program (Marie Curie Actions) of the European Union's Seventh Framework Program FP7/2007-2013/ under REA Grant Agreement No. 290201 MEDGATE’. We are very grateful to REPSeOL, TGS–NOPEC, and the CSIC-Institut Jaume Almera (http://geodb.ictja.csic.es) for allowing us to use an unpublished seismic data from the Gulf of Cadiz. We thank J. Aguire (UGR, Spain) for comments and suggestions concerning the Pliocene and Quaternary outcrops, B. van den Berg (USAL) for organizing a thought-provoking field-trip to Cadiz, Spain in November, 2014, M. Ángel Caja, L. García Diego, and J. Tritlla (REPSOL) for provenance and diagenetic analysis of early Pliocene sandstones and debrites, and L.J. Lourens (Utrecht University) for providing us the eccentricity and 200-Kys glacio-eustatic sea-level curves included in the Figure 16. Both Prof. D.A.V. Stow (Heriot-Watt Univ., UK) and F.J. Hernández-Molina (RHUL, UK), as the main co-proponents of the IODP Proposal 644 and the co-chiefs of the IODP Exp. 339, thanks to IODP, Exp. IODP 339 Scientists; JR crew and technicians, as well as all people, institutions and companies involved in making IODP a success since 2003. Finally, we also thank the editor, Gert J. De Lange and the reviewers T. Mulder (Bourdeaux Univ.); D. Van Rooij (Ghent Univ) and J. Duarte (Monash Univ.) for their very positive and helpful feedback and discussions in publishing this research.Peer reviewedPublisher PD

Corrosion behaviour of micro-plasma arc welded stainless steels in H3PO4 under flowing conditions at different temperatures

[EN] This paper studies the general corrosion behaviour of the micro-plasma arc welded AISI 316L stainless steel in phosphoric acid at different temperatures (25-60°C) and at a Reynolds number of 1456. Galvanic corrosion has been studied using zero-resistance ammeter (ZRA) measurements and polarization curves (by the mixed potential theory). Results show that the microstructure of the stainless steel is modified due to the micro-plasma arc welding procedure. Coupled current density values obtained from polarization curves increase with temperature. ZRA tests present the highest iG values at 60°C; however, the values are very close to zero for all the temperatures studied. This is in agreement with the low value of the compatibility limit and of the parameter which evaluates the importance of the galvanic phenomenon. Both techniques present the most positive potentials at the highest temperature. This study reveals that micro-plasma arc welded AISI 316L stainless steels are appropriated working in the studied H3PO4 media from a corrosion point of view for all the temperatures analysedThe authors would like to express their gratitude to the Spanish MAEC (PCI Mediterráneo C/8196/07, C/018046/08, D/023608/09) and to Asuncion Jaime for her translation assistance.Sánchez Tovar, R.; Montañés Sanjuan, MT.; García Antón, J.; Guenbour, A.; Ben Bachir, A. (2011). Corrosion behaviour of micro-plasma arc welded stainless steels in H3PO4 under flowing conditions at different temperatures. Corrosion Science. 53(4):1237-1246. https://doi.org/10.1016/j.corsci.2010.12.017S1237124653

Regional development gaps in Argentina: A multidimensional approach to identify the location of policy priorities

Spatial inequalities within Latin American countries have historically attracted the interest ofacademics, policy-makers, and international agencies. This article aims to provide amultidimensional diagnosis of provincial development gaps in Argentina, in order to identifythe location of policy priorities. Therefore, we built a large database, which covers sevendevelopment dimensions, and applied multivariate analysis techniques to overcome someanalytical limitations of previous studies. Results show the stability of provincial developmentgaps between 2003 and 2013 and some heterogeneity within geographic regions. Instead,cluster analysis offers a better classification of Argentine provinces according to theirdevelopment gaps, which can help the government to prioritize the places wheredevelopment policies are strategic.Fil: Niembro, Andrés Alberto. Consejo Nacional de Investigaciones Científicas y Técnicas. Centro Científico Tecnológico Conicet - Patagonia Norte; Argentina. Universidad Nacional de Río Negro; ArgentinaFil: Sarmiento, Jesica Isabel. Consejo Nacional de Investigaciones Científicas y Técnicas. Centro Científico Tecnológico Conicet - Patagonia Norte; Argentina. Universidad Nacional de Río Negro; Argentin

Asymptomatic internal carotid artery stenosis and cerebrovascular risk stratification

Background The purpose of this study was to determine the cerebrovascular risk stratification potential of baseline degree of stenosis, clinical features, and ultrasonic plaque characteristics in patients with asymptomatic internal carotid artery (ICA) stenosis. Methods This was a prospective, multicenter, cohort study of patients undergoing medical intervention for vascular disease. Hazard ratios for ICA stenosis, clinical features, and plaque texture features associated with ipsilateral cerebrovascular or retinal ischemic (CORI) events were calculated using proportional hazards models. Results A total of 1121 patients with 50% to 99% asymptomatic ICA stenosis in relation to the bulb (European Carotid Surgery Trial [ECST] method) were followed-up for 6 to 96 months (mean, 48). A total of 130 ipsilateral CORI events occurred. Severity of stenosis, age, systolic blood pressure, increased serum creatinine, smoking history of more than 10 pack-years, history of contralateral transient ischemic attacks (TIAs) or stroke, low grayscale median (GSM), increased plaque area, plaque types 1, 2, and 3, and the presence of discrete white areas (DWAs) without acoustic shadowing were associated with increased risk. Receiver operating characteristic (ROC) curves were constructed for predicted risk versus observed CORI events as a measure of model validity. The areas under the ROC curves for a model of stenosis alone, a model of stenosis combined with clinical features and a model of stenosis combined with clinical, and plaque features were 0.59 (95% confidence interval [CI] 0.54-0.64), 0.66 (0.62-0.72), and 0.82 (0.78-0.86), respectively. In the last model, stenosis, history of contralateral TIAs or stroke, GSM, plaque area, and DWAs were independent predictors of ipsilateral CORI events. Combinations of these could stratify patients into different levels of risk for ipsilateral CORI and stroke, with predicted risk close to observed risk. Of the 923 patients with <70% stenosis, the predicted cumulative 5-year stroke rate was <5% in 495, 5% to 9.9% in 202, 10% to 19.9% in 142, and <20% in 84 patients. Conclusion Cerebrovascular risk stratification is possible using a combination of clinical and ultrasonic plaque features. These findings need to be validated in additional prospective studies of patients receiving optimal medical intervention alone. Copyright © 2010 by the Society for Vascular Surgery

The size of juxtaluminal hypoechoic area in ultrasound images of asymptomatic carotid plaques predicts the occurrence of stroke

Objective: To test the hypothesis that the size of a juxtaluminal black (hypoechoic) area (JBA) in ultrasound images of asymptomatic carotid artery plaques predicts future ipsilateral ischemic stroke. Methods: A JBA was defined as an area of pixels with a grayscale value &lt;25 adjacent to the lumen without a visible echogenic cap after image normalization. The size of a JBA was measured in the carotid plaque images of 1121 patients with asymptomatic carotid stenosis 50% to 99% in relation to the bulb (Asymptomatic Carotid Stenosis and Risk of Stroke study); the patients were followed for up to 8 years. Results: The JBA had a linear association with future stroke rate. The area under the receiver-operating characteristic curve was 0.816. Using Kaplan-Meier curves, the mean annual stroke rate was 0.4% in 706 patients with a JBA &lt;4 mm 2, 1.4% in 171 patients with a JBA 4 to 8 mm2, 3.2% in 46 patients with a JBA 8 to 10 mm2, and 5% in 198 patients with a JBA &gt;10 mm2 (P &lt;.001). In a Cox model with ipsilateral ischemic events (amaurosis fugax, transient ischemic attack [TIA], or stroke) as the dependent variable, the JBA (&lt;4 mm2, 4-8 mm2, &gt;8 mm2) was still significant after adjusting for other plaque features known to be associated with increased risk, including stenosis, grayscale median, presence of discrete white areas without acoustic shadowing indicating neovascularization, plaque area, and history of contralateral TIA or stroke. Plaque area and grayscale median were not significant. Using the significant variables (stenosis, discrete white areas without acoustic shadowing, JBA, and history of contralateral TIA or stroke), this model predicted the annual risk of stroke for each patient (range, 0.1%-10.0%). The average annual stroke risk was &lt;1% in 734 patients, 1% to 1.9% in 94 patients, 2% to 3.9% in 134 patients, 4% to 5.9% in 125 patients, and 6% to 10% in 34 patients. Conclusions: The size of a JBA is linearly related to the risk of stroke and can be used in risk stratification models. These findings need to be confirmed in future prospective studies or in the medical arm of randomized controlled studies in the presence of optimal medical therapy. In the meantime, the JBA may be used to select asymptomatic patients at high stroke risk for carotid endarterectomy and spare patients at low risk from an unnecessary operation