Tgfβ2 and 3 are coexpressed with their extracellular regulator Ltbp1 in the early limb bud and modulate mesodermal outgrowth and BMP signaling in chicken embryos

<p>Abstract</p> <p>Background</p> <p>Transforming growth factor β proteins (Tgfβs) are secreted cytokines with well-defined functions in the differentiation of the musculoskeletal system of the developing limb. Here we have studied in chicken embryos, whether these cytokines are implicated in the development of the embryonic limb bud at stages preceding tissue differentiation.</p> <p>Results</p> <p>Immunohistochemical detection of phosphorylated Smad2 and Smad3 indicates that signaling by this pathway is active in the undifferentiated mesoderm and AER. Gene expression analysis shows that transcripts of <it>tgfβ2 </it>and <it>tgfβ3 </it>but not <it>tgfβ1 </it>are abundant in the growing undifferentiated limb mesoderm. Transcripts of <it>tgfβ2 </it>are also found in the AER, which is the signaling center responsible for limb outgrowth. Furthermore, we show that Latent Tgfβ Binding protein 1 (LTBP1), which is a key extracellular modulator of Tgfβ ligand bioavailability, is coexpressed with <it>Tgfβs </it>in the early limb bud. Administration of exogenous Tgfβs to limb buds growing in explant cultures provides evidence of these cytokines playing a role in the regulation of mesodermal limb proliferation. In addition, analysis of gene regulation in these experiments revealed that Tgfβ signaling has no effect on the expression of master genes of musculoskeletal tissue differentiation but negatively regulates the expression of the BMP-antagonist Gremlin.</p> <p>Conclusion</p> <p>We propose the occurrence of an interplay between Tgfβ and BMP signaling functionally associated with the regulation of early limb outgrowth by modulating limb mesenchymal cell proliferation.</p

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

Activin/TGFβ and BMP crosstalk determines digit chondrogenesis

AbstractThe progress zone (PZ) is a specialized area at the distal margin of the developing limb where mesodermal cells are kept in proliferation and undifferentiated, allowing limb outgrowth. At stages of digit morphogenesis the PZ cells can undergo two possible fates, either aggregate initiating chondrogenic differentiation to configure the digit blastemas, or to die by apoptosis if they are incorporated in the interdigital mesenchyme. While both processes are controlled by bone morphogenetic proteins (BMPs) the molecular basis for such contrasting differential behavior of the autopodial mesoderm remains unknown. Here we show that a well-defined crescent domain of high BMP activity located at the tip of the forming digits, which we termed the digit crescent (DC), directs incorporation and differentiation of the PZ mesenchymal cells into the digit aggregates. The presence of this domain does not correlate with an exclusive expression domain of BMP receptors and its abrogation by surgical approaches or by local application of BMP antagonists is followed by digit truncation and cell death. We further show that establishment of the DC is directed by Activin/TGFβ signaling, which inhibits Smad 6 and Bambi, two specific BMP antagonists expressed in the interdigits and progress zone mesoderm. The interaction between Activin/TGFβ and BMP pathways at the level of DC promotes the expression of the chondrogenic factor SOX9 accompanied by a local decrease in cell proliferation. Characteristically, the DC domain is asymmetric, it being extended towards the posterior interdigit. The presence of the DC is transitorily dependent of the adjacent posterior interdigit and its maintenance requires also the integrity of the AER

Beyond global nodes and economic indicators in the evaluation of the world-system of cities

The paper aims to look at the organisation of the world-urban system. It proposes an integrated explorative approach which, in addition to considering economic-production type indicators, includes others that can reflect a complex approach to functional and geographic specialisation. Methodologically, the comparative analysis of three synthetic indices through a cluster analysis allows for the multifunctional representation of the world-urban system, in which other centralities and cities excluded from other rankings are considered. The first index is taken from the proposal by the GaWC (Global and World Cities Research Network). The second relates to cultural services and some of the knowledgeintensive activities. The third includes variables related to mobility, more specifically air transport. The comparison of functions, as revealed by the indices, can provide information about how cities work in the world context. The analysis allows for the identification of a group of prominent multifunctional cities at the top, and a large group of less prominent and specialised cities underneath

Activin/TGFβ and BMP crosstalk determines digit chondrogenesis

AbstractThe progress zone (PZ) is a specialized area at the distal margin of the developing limb where mesodermal cells are kept in proliferation and undifferentiated, allowing limb outgrowth. At stages of digit morphogenesis the PZ cells can undergo two possible fates, either aggregate initiating chondrogenic differentiation to configure the digit blastemas, or to die by apoptosis if they are incorporated in the interdigital mesenchyme. While both processes are controlled by bone morphogenetic proteins (BMPs) the molecular basis for such contrasting differential behavior of the autopodial mesoderm remains unknown. Here we show that a well-defined crescent domain of high BMP activity located at the tip of the forming digits, which we termed the digit crescent (DC), directs incorporation and differentiation of the PZ mesenchymal cells into the digit aggregates. The presence of this domain does not correlate with an exclusive expression domain of BMP receptors and its abrogation by surgical approaches or by local application of BMP antagonists is followed by digit truncation and cell death. We further show that establishment of the DC is directed by Activin/TGFβ signaling, which inhibits Smad 6 and Bambi, two specific BMP antagonists expressed in the interdigits and progress zone mesoderm. The interaction between Activin/TGFβ and BMP pathways at the level of DC promotes the expression of the chondrogenic factor SOX9 accompanied by a local decrease in cell proliferation. Characteristically, the DC domain is asymmetric, it being extended towards the posterior interdigit. The presence of the DC is transitorily dependent of the adjacent posterior interdigit and its maintenance requires also the integrity of the AER

Treatment of epidermoid tumors with gamma knife radiosurgery: case series

Epidermoid tumors (ETs) are benign lesions that are treated mainly by means of surgical resection, with overall good results. External beam radiotherapy is an alternative treatment for those recurrent tumors, in which a second surgery might not be the best choice for the patient. A little information exists about the effectiveness of gamma knife radiosurgery for the treatment of newly diagnosed and recurrent ETs. We present three cases of ETs treated with gamma knife radiosurger

A review on coastal urban ecology: research gaps, challenges, and needs

Coastal urban areas have dramatically increased during the last decades, however, coastal research integrating the impacts and challenges facing urban areas is still scarce. To examine research advances and critical gaps, a review of the literature on coastal urban ecology was performed. Articles were selected following a structured decision tree and data were classified into study disciplines, approaches, type of analysis, main research objectives, and Pickett's paradigms in-, of-, and for- the city, among other categories. From a total of 237 publications, results show that most of the research comes from the USA, China, and Australia, and has been carried out mostly in large cities with populations between 1 and 5 million people. Focus has been placed on ecological studies, spatial and quantitative analysis and pollution in coastal urban areas. Most of the studies on urban ecology in coastal zones were developed at nearshore terrestrial environments and only 22.36% included the marine ecosystem. Urban ecological studies in coastal areas have mainly been carried out under the paradigm in the city with a focus on the disciplines of biology and ecology. Results suggest a series of disciplinary, geographical, and approach biases which can present a number of risks. Foremost among these is a lack of knowledge on social dimensions which can impact on sustainability. A key risk relates to the fact that lessons and recommendations of research are mainly from developed countries and large cities which might have different institutional, planning and cultural settings compared to developing and mid-income countries. Scientific research on coastal urban areas needs to diversify toward an ecology of and for the cities, in order to support coastal development in a diversity of countries and settings

Tunnelling in quantum superlattices with variable lacunarity

Quantum fractal superlattices are microelectronic devices consisting of a series of thin layers of two semiconductor materials deposited alternately on each other over a substrate following the rules of construction of a fractal set, here, a symmetrical polyadic Cantor fractal. The scattering properties of electrons in these superlattices may be modeled by using that of quantum particles in piecewise constant potential wells. The twist plots representing the reflection coefficient as function of the lacunarity parameter show the appearance of black curves with perfectly transparent tunnelling which may be classified as vertical, arc, and striation nulls. Approximate analytical formulae for these reflection-less curves are derived using the transfer matrix method. Comparison with the numerical results show their good accuracy.Comment: 12 pages, 3 figure

Laser transmission welding as an assembling process for high temperature electronic packaging.

Higher efficiency, power density, reliability and longer lifetime of power electronic devices would stem from progresses in material science. In this work, we propose to use a high performance thermoplastic polymer PAEK as packaging box to extend the operating temperature above 200°C. More, the laser transmission welding process has been applied to PAEK to join the two-part module. In order to validate this assembling process, the temperature distribution inside the specimens was measured during laser transmission welding. The assembly consists of a quasi-amorphous sample as the upper part and a semi-crystalline sample as the lower part. The temperature fields were measured by infrared thermography with the camera sensor perpendicular to the welded interface. With an energy beam of 28 J.mm-2 and irradiation time of 15 s, we have noticed that the maximum temperature inside the sample is kept far from the PAEK degradation one. Moreover, the temperature at the interface reaches the melting temperature thus assuring enough mobility for polymeric chains to get adhesion at the interface. The location and size of the heat-affected zone has been determined. Finally, some frames were machined and successfully welded

Impacto del equipo multidisciplinario “ECMO Team” en el pronóstico de pacientes sometidos a membrana de oxigenación extracorpórea venoarterial por choque cardiogénico o paro cardiorrespiratorio refractario

Objectives. Veno-arterial Extracorporeal membrane oxygenation (VA ECMO) is a salvage intervention in patients with cardiogenic shock (CS), and cardiac arrest  (CA) refractory to standard therapies. The design of ECMO Teams has achieved the standardization of processes, although its impact on survival and prognosis is unknown. Objective: We aimed to analyze whether the creation of an ECMO Team has modified the prognosis of patients undergoing VA ECMO for refractory CS or CA. Materials and methods. We conducted a single-center retrospective cohort study. Patients with refractory CS or CA who underwent VA ECMO were divided in two consecutive periods: from 2014 to April 2019 (pre-ECMO T) and from May 2019 to December 2022 (Post ECMO T). The main outcomes were survival on ECMO, in-hospital survival, complications, and annual ECMO volume. Results. Eighty-three patients were included (36 pre-ECMO T and 47 post-ECMO T). The mean age was 53 +/-13 years. The most common reason for  device indication was different:  postcardiotomy shock (47.2%) pre-ECMO T and refractory cardiogenic shock (29.7%) post-ECMO T. The rate of extracorporeal  cardiopulmonary resuscitation was 14.5%.  The median duration of VA ECMO was longer after ECMO team implementation: 8 days (IQR 5-12.5) vs. five days (IQR 2-9, p=0.04). Global in-hospital survival was 45.8% (38.9% pre-ECMO T vs. 51.1% post-ECMO T; p=0.37),  and the survival rate from VA ECMO was 60.2% (55.6% pre-ECMO T vs 63.8% post-ECMO T; p= 0.50). The volume of VA ECMO implantation was significantly higher in the post-ECMO team period (13.2  +/3.5 per year vs. 6.5 +/-3.5 per year, p: 0.02). The rate of complications was similar in both groups. Conclusions. After the implementation of an ECMO team, there was no statistical difference in the survival rate of patients treated with VA ECMO. However, a significant increase in the number of patients supported per year was observed after the implementation of this multidisciplinary team. Post-ECMO T, the most common reason for device indication was cardiogenic shock, with longer run times and a higher rate of extracorporeal cardiopulmonary resuscitation.Introducción. La oxigenación por membrana extracorpórea venoarterial (ECMO VA) es una intervención de rescate utilizada en choque cardiogénico (CC) o paro cardiorrespiratorio (PCR) refractario. La creación de equipos multidisciplinarios ECMO Teams (ECMO T), ha permitido la estandarización de procesos, aunque se desconoce su impacto en  sobrevida y pronóstico. Objetivo: El propósito es analizar si la creación del ECMO Team ha modificado el pronóstico de los pacientes sometidos a ECMO VA por CC o PCR refractario. Materiales y métodos. Estudio observacional, unicéntrico, retrospectivo, que comparó los resultados del implante de ECMO VA por CC o PCR refractario en dos períodos consecutivos: entre 2014 y abril de 2019 (pre-ECMO T), y entre mayo de 2019 y diciembre de 2022 (pos-ECMO T). Como puntos finales, se evaluó la sobrevida intrahospitalaria y en ECMO, complicaciones, y volumen de ECMO anual. Resultados. Se analizaron 83 pacientes (36 pre-ECMO T, y 47 pos-ECMO T), con edad de 53 +/-13 años. La causa más frecuente de asistencia fue: poscardiotomía pre-ECMO T (47,2%) y CC refractario pos-ECMO T (29,7%). En el 14,5% se realizó ECMO en PCR. La mediana de asistencia fue mayor pos-ECMO T (8 días, RIC 5-12,5 vs. 5 días, RIC 2-9 pre-ECMO T; p:0,04). La supervivencia al alta fue del 45,8% (38,9% pre-ECMO T vs. 51,1% pos-ECMO T;p:0,37) y en ECMO VA del 60,2% (55,6% pre-ECMO T y 63,8% pos-ECMO T; p:0,50). El volumen de ECMO VA fue significativamente mayor pos-ECMO T (13,2+/3,5 por año vs. 6,5+/-3,5 por año, p: 0,02). La tasa de complicaciones fue similar en ambos períodos. Conclusiones.Luego de la implementación del ECMO Team no se observó una diferencia significativa en la sobrevida en pacientes asistidoscon ECMO VA. Sin embargo, luego de su creación se evidenció un aumento significativo del volumen de pacientes asistidos por año. Pos-ECMO T se asistió mayor número de pacientes por choque cardiogénico, en PCR y con más días de asistencia