BMP signaling in telencephalic neural cell specification and maturation

Bone morphogenetic proteins (BMPs) make up a family of morphogens that are critical for patterning, development, and function of the central and peripheral nervous system. Their effects on neural cells are pleiotropic and highly dynamic depending on the stage of development and the local niche. Neural cells display a broad expression profile of BMP ligands, receptors, and transducer molecules. Moreover, interactions of BMP signaling with other incoming morphogens and signaling pathways are crucial for most of these processes. The key role of BMP signaling suggests that it includes many regulatory mechanisms that restrict BMP activity both temporally and spatially. BMPs affect neural cell fate specification in a dynamic fashion. Initially they inhibit proliferation of neural precursors and promote the first steps in neuronal differentiation. Later on, BMP signaling effects switch from neuronal induction to promotion of astroglial identity and inhibition of neuronal or oligodendroglial lineage commitment. Furthermore, in postmitotic cells, BMPs regulate cell survival and death, to modulate neuronal subtype specification, promote dendritic and axonal growth and induce synapse formation and stabilization. In this review, we examine the canonical and non-canonical mechanisms of BMP signal transduction. Moreover, we focus on the specific role of BMPs in the nervous system including their ability to regulate neural stem cell proliferation, self-renewal, lineage specification, and neuronal function

Creación de alternativas productivas al modelo de la soja RR a partir de los criterios definidos por la población de Basavilbaso, Argentina

El consumo desmesurado de energía por parte de los países del Norte lleva a la creación de una deuda ecológica en los países del Sur. Ésta se debe, entre otros factores, al modelo agrario introducido con la "Nueva Revolución Verde". En Argentina los monocultivos de sojaRR están potenciando la pérdida de la soberanía alimentaria en todo el país. Al mismo tiempo, las políticas energéticas europeas van a provocar una subida en la demanda de materias primas para la producción de biocombustible, lo que llevará a un aumento de la superficie de sojaRR en Argentina. El objetivo de este estudio es la creación de alternativas productivas mediante la implicación de la población de un municipio argentino. A través de la metodología de análisis social "CLIP" se han identificado los diferentes actores implicados en el modelo agrario que a lo largo del trabajo plantean propuestas de cambio para el sector agropecuario de su municipio. El resultado ha sido el planteamiento de cuatro grandes alternativas: la agricultura orgánica, la rotación de actividades, las producciones avícolas y apícolas y la diversificación de cultivos energéticos. Viendo que la tipología de consumo del Norte afecta directamente en la vida de los países del Sur, en todas las alternativas propuestas en este caso de estudio, se acaba por apostar por la creación de redes productivas y comerciales locales que potencien los beneficios en los países productores sin abandonar las posibilidades del mercado internacional.El desmesurat consum d'energia per part dels països del Nord porta a la creació d'un deute ecològic en els països del Sud. Aquest es degut, entre d'altres factors, al model agrari introduït amb la "Nova Revolució Verda". A Argentina els monocultius de sojaRR estan potenciant la pèrdua de la sobirania alimentaria a tot el país. A l'hora, les polítiques energètiques europees provocaran una pujada de la demanda de matèries primeres per la producció de biocombustibles, fet que donarà lloc a un augment de la superfície de sojaRR a Argentina. L'objectiu d'aquest estudi és la creació d'alternatives productives a través de la implicació de la població d'un municipi argentí. Mitjançant la metodologia d'anàlisi social "CLIP" s'identificaran els diferents actors implicats en la situació d'estudi que en el transcurs del treball plantejaran propostes pel sector agropecuari del seu municipi. El resultat serà el plantejament de quatre grans alternatives: l'agricultura orgànica, la rotació d'activitats, les produccions avícoles i apícoles i la diversificació de cultius energètics. Veient que la tipologia de consum del Nord afecta directament a la vida dels països del Sud, en totes les alternatives proposades en aquest cas d'estudi, s'acaba apostant per la creació de xarxes productives i comercials locals que potencien els beneficis en els països productors sense abandonar les possibilitats del mercat internacional.Energy overconsumption in Northern countries results in ecological debt in the southern Hemisphere, due in part to the "New Green Revolution" agrarian model in Argentina. RR Soybean single crop enhance the loss of food sovereignty across the country. European energy policies will lead to an increase in the demand of primary products to generate biofuel, resulting in an increase of soybean production in Argentina. Here we discuss the generation of alternatives through community involvement in a case study. Here we have identified different players involved in the agricultural model that generate proposals of change through this work by CLIP social analysis. The result of this study is the proposal of four different alternatives, namely organic agriculture production, rotation of agrarian activities, poultry or beehive development and diversification of biofuel farms. Since consumption in the Northern hemisphere affects directly life in southern countries in all the alternative considered here we propose the generation of productive networks and local merchants that enhance the benefits in producing countries, without ignoring the possibilities of the global market

Extracellular calcium promotes bone formation from bone marrow mesenchymal stem cells by amplifying the effects of BMP-2 on SMAD signalling

Understanding the molecular events that regulate osteoblast differentiation is essential for the development of effective approaches to bone regeneration. In this study, we analysed the osteoinductive properties of extracellular calcium in bone marrow-derived mesenchymal stem cell (BM-MSC) differentiation. We cultured BM-MSCs in 3D gelatin scaffolds with Ca2+ and BMP-2 as osteoinductive agents. Early and late osteogenic gene expression and bone regeneration in a calvarial critical-size defect model demonstrate that extracellular Ca2+ enhances the effects of BMP-2 on Osteocalcin, Runx2 and Osterix expression and promotes bone regeneration in vivo. Moreover, we analysed the molecular mechanisms involved and observed an antagonistic effect between Ca2+ and BMP-2 on SMAD1/5, ERK and S6K signalling after 24 hours. More importantly, a cooperative effect between Ca2+ and BMP-2 on the phosphorylation of SMAD1/5, S6, GSK3 and total levels of β-CATENIN was observed at a later differentiation time (10 days). Furthermore, Ca2+ alone favoured the phosphorylation of SMAD1, which correlates with the induction of Bmp2 and Bmp4 gene expression. These data suggest that Ca2+ and BMP-2 cooperate and promote an autocrine/paracrine osteogenic feed-forward loop. On the whole, these results demonstrate the usefulness of calcium-based bone grafts or the addition of exogenous Ca2+ in bone tissue engineering

MicroRNA-322 (miR-322) and its target protein Tob2 modulate Osterix (Osx) mRNA stability

Osteogenesis depends on a coordinated network of signals and transcription factors such as Runx2 and Osterix. Recent evidence indicates that microRNAs (miRNAs) act as important post-transcriptional regulators in a large number of processes, including osteoblast differentiation. In this study, we performed miRNA expression profiling and identified miR-322, a BMP-2-down-regulated miRNA, as a regulator of osteoblast differentiation. We report miR-322 gain- and loss-of-function experiments in C2C12 and MC3T3-E1 cells and primary cultures of murine bone marrow-derived mesenchymal stem cells. We demonstrate that overexpression of miR-322 enhances BMP-2 response, increasing the expression of Osx and other osteogenic genes. Furthermore, we identify Tob2 as a target of miR-322, and we characterize the specific Tob2 3′-UTR sequence bound by miR-322 by reporter assays. We demonstrate that Tob2 is a negative regulator of osteogenesis that binds and mediates degradation of Osx mRNA. Our results demonstrate a new molecular mechanism controlling osteogenesis through the specific miR-322/Tob2 regulation of specific target mRNAs. This regulatory circuit provides a clear example of a complex miRNA-transcription factor network for fine-tuning the osteoblast differentiation program

p38 MAPK signaling in osteoblast differentiation

The skeleton is a highly dynamic tissue whose structure relies on the balance between bone deposition and resorption. This equilibrium, which depends on osteoblast and osteoclast functions, is controlled by multiple factors that can be modulated post-translationally. Some of the modulators are Mitogen-activated kinases (MAPKs), whose role has been studied in vivo and in vitro. p38-MAPK modifies the transactivation ability of some key transcription factors in chondrocytes, osteoblasts and osteoclasts, which affects their differentiation and function. Several commercially available inhibitors have helped to determine p38 action on these processes. Although it is frequently mentioned in the literature, this chemical approach is not always as accurate as it should be. Conditional knockouts are a useful genetic tool that could unravel the role of p38 in shaping the skeleton. In this review, we will summarize the state of the art on p38 activity during osteoblast differentiation and function, and emphasize the triggers of this MAPK

Biological parameters, ecology and population trends of the Mediterranean endemic skate, Raja polystigma, in the Balearic Islands

Elasmobranchs are a vulnerable group that has been overexploited for almost half a century in the Mediterranean. However, few elasmobranch species have been assessed because information on their basic biological parameters is lacking for most species. Raja polystigma is a poorly studied endemic skate in the Mediterranean. The aim of this work is to determine some basic life history parameters of this skate in the Balearic Islands. Data were collected from commercial catches and during MEDITS surveys. Total length varied from 17 to 59 cm for both sexes, with a higher proportion of females than males. Allometric and morphometric relationships differed between sexes, females being heavier for a given size. Females matured at a larger size than males (L50 47.7 cm and 38.4 cm, respectively). Potential fecundity ranged between 11 and 45 yolked oocytes per female, and spawning was observed mainly during winter and spring. Persistent hotspots of adults and juveniles were detected on the shallow shelf off the northwest of Mallorca and east of Menorca, with adults being found mainly in the shallow and juveniles in deeper areas. Time series of abundance and frequency of appearance showed stable trends throughout the study period (2003-2018).En prensa1,00

Effect of apparent depth cues on accommodation in a Badal optometer

Background: The aim was to analyse the effect of peripheral depth cues on accommodation in Badal optometers. Methods: Monocular refractions at 0.17 and 5.00 D of accommodative stimulus were measured with the PowerRef II autorefractor (Plusoptix Inc., Atlanta, Georgia, USA). Subjects looked (randomly) at four different scenes, one real scene comprising familiar objects at different depth planes (Real) and three virtual scenes comprising different two-dimensional pictures seen through a Badal lens. The first image consisted of a photograph of the real scene taken in conditions that closely mimic a healthy standard human eye performance (out-of-focus [OoF] blur); the second image was the same photograph rendered with a depth of focus to infinity (OoF sharpness); and finally the third image consisted of a fixation target and a even white surrounding (White). In all cases the field of view was 25.0° and the fixation target was a Maltese cross subtending to two degrees. Results: Twenty-eight right eyes from healthy young subjects were measured. The achieved statistical power was 0.9. At 5.00 D of accommodative stimulus, the repeated measures analysis of variance was statistically significant (p¿<¿0.05) and the corresponding Bonferroni post hoc tests showed the following mean accommodative response differences and standard deviation (p-value) between the real and the virtual scenes: real-white¿=-0.66¿±¿0.92 D (p¿<¿0.01); real-OoF sharpness¿=¿-0.43¿±¿0.88 D (p¿=¿0.07); real-OoF blur¿=-0.25¿±¿0.93 D (p¿=¿0.89). Conclusions: A stimulus poor in depth cues inaccurately stimulates accommodation in Badal optometers; however, accommodation can be significantly improved in the same Badal optometer, when displaying a realistic image rich in peripheral depth cues, even though these peripheral cues (also referred to as retinal blur cues) are shown in the same plane as the fixation target. These results have important implications in stereoscopic virtual reality systems that fail to represent appropriately retinal blur.Preprin

The p38α MAPK function in osteoprecursors is required for bone formation and bone homeostasis in adult mice

p38 MAPK activity plays an important role in several steps of the osteoblast lineage progression through activation of osteoblast-specific transcription factors and it is also essential for the acquisition of the osteoblast phenotype in early development. Although reports indicate p38 signalling plays a role in early skeletal development, its specific contributions to adult bone remodelling are still to be clarified. Methodology/Principal Findings: We evaluated osteoblast-specific deletion of p38 alpha to determine its significance in early skeletogenesis, as well as for bone homeostasis in adult skeleton. Early p38 alpha deletion resulted in defective intramembranous and endochondral ossification in both calvaria and long bones. Mutant mice showed reduction of trabecular bone volume in distal femurs, associated with low trabecular thickness. In addition, knockout mice also displayed decreased femoral cortical bone volume and thickness. Deletion of p38 alpha did not affect osteoclast function. Yet it impaired osteoblastogenesis and osteoblast maturation and activity through decreased expression of osteoblast-specific transcription factors and their targets. Furthermore, the inducible Cre system allowed us to control the onset of p38 alpha disruption after birth by removal of doxycycline. Deletion of p38 alpha at three or eight weeks postnatally led to significantly lower trabecular and cortical bone volume after 6 or 12 months. Conclusions: Our data demonstrates that, in addition to early skeletogenesis, p38 alpha is essential for osteoblasts to maintain their function in mineralized adult bone, as bone anabolism should be sustained throughout life. Moreover, our data also emphasizes that clinical development of p38 inhibitors should take into account their potential bone effects

What does the media say about palliative care? A descriptive study of news coverage in written media in Spain

INTRODUCTION: The goal of palliative care (PC) is to improve the quality of life of terminal stage patients and their families. The subject frequently appears in the mass-media and this helps create a socially accepted identity. The aim of this study is to describe and analyse PC related news items appeared in the Spanish written media. METHODOLOGY: A descriptive cross-sectional study was designed. Considering diffusion, scope and the range in editorial policy criteria, four printed newspapers (PN) were selected, together with four exclusively digital media sources (DM). Through Mynews, a newspaper content depository, and the search tool for each DM website, articles published between 2009 and 2014 which included the terms "palliative care" and "palliative medicine" were sought. A questionnaire was created to characterise each article identified and a descriptive analysis was undertaken. RESULTS: A total of 627 articles were identified, of which 359 (57%) were published in PN (42% in the printed editions -PE- 16% in their online editions -OE-) and 268 (43%) in DM. In general, they appeared mainly in sections concerning Health (23%), Culture and Society (18%) and General/Home News (15%). In PE, just 2% were found in the Health section and nearly 70% in Culture and Society and General/Home News. Most of the articles were informative in nature and contained socio-political messages (90%). Statements by PC professionals were found in 35% of the articles and by politicians in 32%. The most frequent content was related to facing end of life (74%) and patient quality of life (70%). CONCLUSIONS: The Spanish written media reflects the socio-political interest aroused by PC. Nevertheless, messages circulating about PC do not describe professional practice, or the contribution of the same for patients. Content more in line with the clinical practice might help contribute to the development of this new area of medicine

Comparative Analysis of TCR-gamma Gene Rearrangements by Genescan and Polyacrylamide Gel-electrophoresis in Cutaneous T-cell Lymphoma

Demonstrating T-cell clonality has become an important approach supporting a diagnosis of malignant T-cell neoplasms. A comparative study between Genescan analysis, polyacrylamide gel and agarose gel electrophoresis in visualizing X-cell receptor gamma gene rearrangement was performed on 25 biopsy specimens from 18 patients with different forms of cutaneous T-cell lymphomas. Clonality was detected in 17 biopsy specimens when PCR products were evaluated by Genescan analysis. Seventeen showed discrete bands when visualized in polyacrylamide gel and 14 cases were clonal when visualized with agarose gel. In five cases, a clonal population was seen in the gels, but not with Genescan. On sequencing the PCR products we demonstrated nonclonality of these five samples. Our results confirm that PCR-Genescan is a useful, reliable and specific screening method for detecting dominant clones in patients with T-cell lymphoma