Alginate Hydrogels as Scaffolds and Delivery Systems to Repair the Damaged Spinal Cord

Alginate (ALG) is a lineal hydrophilic polysaccharide present in brown algae cell walls, which turns into a gel state when hydrated. Gelation readily produces a series of three dimensional (3D) architectures like fibers, capillaries, and microspheres, used as biosensors and bio‐actuators in a plethora of biomedical applications like drug delivery and wound healing. Hydrogels have made a great impact on regenerative medicine and tissue engineering because they are able to mimic the mechanical properties of natural tissues due to their high water content. Recent advances in neurosciences have led to promising strategies for repairing and/or regenerating the damaged nervous system. Spinal cord injury (SCI) is particularly challenging, owing to its devastating medical, human, and social consequences. Although effective therapies to repair the damaged spinal cord (SC) are still lacking, multiple pharmacological, genetic, and cell‐based therapies are currently under study. In this framework, ALG hydrogels constitute a source of potential tools for the development of implants capable of promoting axonal growth and/or delivering cells or drugs at specific damaged sites, which may result in therapeutic strategies for SCI. In this mini‐review, the current state of the art of ALG applications in neural tissues for repairing the damaged spinal cord is discussed

The Betic Ophiolites and the Mesozoic Evolution of the Western Tethys

The Betic Ophiolites consist of numerous tectonic slices, metric to kilometric in size, of eclogitized mafic and ultramafic rocks associated to oceanic metasediments, deriving from the Betic oceanic domain. The outcrop of these ophiolites is aligned along 250 km in the Mulhacen Complex of the Nevado-Filabride Domain, located at the center-eastern zone of the Betic Cordillera (SE Spain). According to petrological/geochemical inferences and SHRIMP (Sensitive High Resolution Ion Micro-Probe) dating of igneous zircons, the Betic oceanic lithosphere originated along an ultra-slow mid-ocean ridge, after rifting, thinning and breakup of the preexisting continental crust. The Betic oceanic sector, located at the westernmost end of the Tethys Ocean, developed from the Lower to Middle Jurassic (185-170 Ma), just at the beginning of the Pangaea break-up between the Iberia-European and the Africa-Adrian plates. Subsequently, the oceanic spreading migrated northeastward to form the Ligurian and Alpine Tethys oceans, from 165 to 140 Ma. Breakup and oceanization isolated continental remnants, known as the Mesomediterranean Terrane, which were deformed and affected by the Upper Cretaceous-Paleocene Eo-Alpine high-pressure metamorphic event, due to the intra-oceanic subduction of the Jurassic oceanic lithosphere and the related continental margins. This process was followed by the partial exhumation of the subducted oceanic rocks onto their continental margins, forming the Betic and Alpine Ophiolites. Subsequently, along the Upper Oligocene and Miocene, the deformed and metamorphosed Mesomediterranean Terrane was dismembered into different continental blocks collectively known as AlKaPeCa microplate (Alboran, Kabylian, Peloritan and Calabrian). In particular, the Alboran block was displaced toward the SW to occupy its current setting between the Iberian and African plates, due to the Neogene opening of the Algero-Provencal Basin. During this translation, the different domains of the Alboran microplate, forming the Internal Zones of the Betic and Rifean Cordilleras, collided with the External Zones representing the Iberian and African margins and, together with them, underwent the later alpine deformation and metamorphism, characterized by local differences of P-T (Pressure-Temperature) conditions. These Neogene metamorphic processes, known as Meso-Alpine and Neo-Alpine events, developed in the Nevado-Filabride Domain under Ab-Ep amphibolite and greenschists facies conditions, respectively, causing retrogradation and intensive deformation of the Eo-Alpine eclogites.This research was funded by Project CGL2009-12369 of the Spanish Ministry of Science and Innovation, co-financed with FEDER funds, and by Research Group RNM 333 of Junta de Andalucía (Spain)

Ghrelin's effects on proinflammatory cytokine mediated apoptosis and their impact on β-cell functionality

Ghrelin is a peptidic hormone, which stimulates cell proliferation and inhibits apoptosis in several tissues, including pancreas. In preclinical stage of type 1 diabetes, proinflammatory cytokines generate a destructive environment for β-cells known as insulitis, which results in loss of β-cell mass and impaired insulin secretion, leading to diabetes. Our aim was to demonstrate that ghrelin could preserve β-cell viability, turnover rate, and insulin secretion acting as a counter balance of cytokines. In the present work we reproduced proinflammatory milieu found in insulitis stage by treating murine cell line INS-1E and rat islets with a cytokine cocktail including IL-1β, IFNγ, and TNFα and/or ghrelin. Several proteins involved in survival pathways (ERK 1/2 and Akt/PKB) and apoptosis (caspases and Bcl-2 protein family and endoplasmic reticulum stress markers) as well as insulin secretion were analyzed. Our results show that ghrelin alone has no remarkable effects on β-cells in basal conditions, but interestingly it activates cell survival pathways, downregulates apoptotic mediators and endoplasmic reticulum stress, and restores insulin secretion in response to glucose when beta-cells are cytokine-exposed. These data suggest a potential role of ghrelin in preventing or slowing down the transition from a preclinical to clinically established diabetes by ameliorating the effects of insulitis on β-cells.This work was funded by a grant by the Andalusian Government (PI 0765-2011).Peer Reviewe

Tuning Proton Conductivity in Alkali Metal Phosphonocarboxylates by Cation Size-Induced and Water-Facilitated Proton Transfer Pathways

The structural and functional chemistry of a family of alkali-metal ions with racemic R,S-hydroxyphosphonoacetate (M-HPAA; M = Li, Na, K, Cs) are reported. Crystal structures were determined by X-ray data (Li+, powder diffraction following an ab initio methodology; Na+, K+, Cs+, single crystal). A gradual increase in dimensionality directly proportional to the alkali ionic radius was observed. [Li3(OOCCH(OH)PO3)-(H2O)4]·H2O (Li-HPAA) shows a 1D framework built up by Li-ligand “slabs” with Li+ in three different coordination environments (4-, 5-, and 6-coordinated). Na-HPAA, Na2(OOCCH(OH)PO3H)(H2O)4, exhibits a pillared layered “house of cards” structure, while K-HPAA, K2(OOCCH(OH)PO3H)(H2O)2, and Cs-HPAA, Cs(HOOCCH(OH)-PO3H), typically present intricate 3D frameworks. Strong hydrogen-bonded networks are created even if no water is present, as is the case in Cs-HPAA. As a result, all compounds show proton conductivity in the range 3.5 × 10−5 S cm−1 (Cs-HPAA) to 5.6 × 10−3 S cm−1 (Na-HPAA) at 98% RH and T = 24 °C. Differences in proton conduction mechanisms, Grothuss (Na+ and Cs+) or vehicular (Li+ and K+), are attributed to the different roles played by water molecules and/or proton transfer pathways between phosphonate and carboxylate groups of the ligand HPAA. Upon slow crystallization, partial enrichment in the S enantiomer of the ligand is observed for Na-HPAA, while the Cs-HPAA is a chiral compound containing only the S enantiomer.Proyectos nacionales MAT2010-15175 y MAT2013-41836-

The interactions of cyanobacterial cytochrome c(6) and cytochrome f, characterized by NMR

Metallo-eiwitte

WFPC2 Observations of Compact Star Cluster Nuclei in Low Luminosity Spiral Galaxies

We have used the Wide Field Planetary Camera 2 aboard the Hubble Space Telescope to image the compact star cluster nuclei of the nearby, late-type, low-luminosity spiral galaxies NGC 4395, NGC 4242, and ESO 359-029. We also analyze archival WFPC2 observations of the compact star cluster nucleus of M33. A comparative analysis of the structural and photometric properties of these four nuclei is presented. All of the nuclei are very compact, with luminosity densities increasing at small radii to the resolution limit of our data. NGC 4395 contains a Seyfert 1 nucleus with a distinct bipolar structure and bright associated filaments which are likely due to [OIII] emission. The M33 nucleus has a complex structure, with elongated isophotes and possible signatures of weak activity, including a jet-like component. The other two nuclei are not known to be active, but share similar physical size scales and luminosities to the M33 and NGC 4395 nuclei. The circumnuclear environments of all four of our program galaxies are extremely diffuse, have only low-to-moderate star formation, and appear to be devoid of large quantities of dust. The central gravitational potentials of the galaxies are also quite shallow, making the origin of these types of `naked' nuclei problematic.Comment: to appear in the July 1999 Astronomical Journal; 38 pages (Latex), 5 tables (postscript), 21 figures (gif); postscript versions of the figures may be obtained via anonymous ftp at ftp://ftp.cv.nrao.edu/NRAO-staff/lmatthew/lanl-nucle

Amendment of the OMERACT ultrasound definitions of joints' features in healthy children when using the DOPPLER technique

Background: Recently preliminary ultrasonography (US) definitions, in B mode, for normal components of pediatric joints have been developed by the OMERACT US group. The aim of the current study was to include Doppler findings in the evaluation and definition of normal joint features that can be visualized in healthy children at different age groups. Methods: A multistep approach was used. Firstly, new additional definitions of joint components were proposed during an expert meeting. In the second step, these definitions, along with the preliminary B-mode-US definitions, were tested for feasibility in an exercise in healthy children at different age groups. In the last step, a larger panel of US experts were invited to join a web-based consensus process in order to approve the developed definitions using the Delphi methodology. A Likert scale of 1-5 was used to assess agreement. Results: Physiological vascularity and fat pad tissue were identified and tested as two additional joint components in healthy children. Since physiological vascularity changes over the time in the growing skeleton, the final definition of Doppler findings comprised separate statements instead of a single full definition. A total of seven statements was developed and included in a written Delphi questionnaire to define and validate the new components. The final definitions for fat pad and physiological vascularity agreed by the group of experts reached 92.9% and 100% agreement respectively in a web survey. Conclusion: The inclusion of these two additional joints components which are linked to detection of Doppler signal in pediatric healthy joints will improve the identification of abnormalities in children with joint pathologies

Comparison of flipped learning and traditional lecture method for teaching digestive system diseases in undergraduate medicine: A prospective non-randomized controlled trial

Introduction: This study examined the effects of a large-scale flipped learning (FL) approach in an undergraduate course of Digestive System Diseases. Methods: This prospective non-randomized trial recruited 404 students over three academic years. In 2016, the course was taught entirely in a Traditional Lecture (TL) style, in 2017 half of the course (Medical topics) was replaced by FL while the remaining half (Surgical topics) was taught by TL and in 2018, the whole course was taught entirely by FL. Academic performance, class attendance and student’s satisfaction surveys were compared between cohorts. Results: Test scores were higher in the FL module (Medical) than in the TL module (Surgical) in the 2017 cohort but were not different when both components were taught entirely by TL (2016) or by FL (2018). Also, FL increased the probability of reaching superior grades (scores >7.0) and improved class attendance and students’ satisfaction. Conclusion: The holistic FL model is more effective for teaching undergraduate clinical gastroenterology compared to traditional teaching methods and has a positive impact on classroom attendances

Genomic analysis of the function of the transcription factor gata3 during development of the Mammalian inner ear

We have studied the function of the zinc finger transcription factor gata3 in auditory system development by analysing temporal profiles of gene expression during differentiation of conditionally immortal cell lines derived to model specific auditory cell types and developmental stages. We tested and applied a novel probabilistic method called the gamma Model for Oligonucleotide Signals to analyse hybridization signals from Affymetrix oligonucleotide arrays. Expression levels estimated by this method correlated closely (p<0.0001) across a 10-fold range with those measured by quantitative RT-PCR for a sample of 61 different genes. In an unbiased list of 26 genes whose temporal profiles clustered most closely with that of gata3 in all cell lines, 10 were linked to Insulin-like Growth Factor signalling, including the serine/threonine kinase Akt/PKB. Knock-down of gata3 in vitro was associated with a decrease in expression of genes linked to IGF-signalling, including IGF1, IGF2 and several IGF-binding proteins. It also led to a small decrease in protein levels of the serine-threonine kinase Akt2/PKB beta, a dramatic increase in Akt1/PKB alpha protein and relocation of Akt1/PKB alpha from the nucleus to the cytoplasm. The cyclin-dependent kinase inhibitor p27(kip1), a known target of PKB/Akt, simultaneously decreased. In heterozygous gata3 null mice the expression of gata3 correlated with high levels of activated Akt/PKB. This functional relationship could explain the diverse function of gata3 during development, the hearing loss associated with gata3 heterozygous null mice and the broader symptoms of human patients with Hearing-Deafness-Renal anomaly syndrome