Tunable injectable alginate-based hydrogel for cell therapy in Type 1 Diabetes Mellitus

Islet transplantation has the potential of reestablishing naturally-regulated insulin production in Type 1 diabetic patients. Nevertheless, this procedure is limited due to the low islet survival after transplantation and the lifelong immunosuppression to avoid rejection. Islet embedding within a biocompatible matrix provides mechanical protection and a physical barrier against the immune system thus, increasing islet survival. Alginate is the preferred biomaterial used for embedding insulin-producing cells because of its biocompatibility, low toxicity and ease of gelation. However, alginate gelation is poorly controlled, affecting its physicochemical properties as an injectable biomaterial. Including different concentrations of the phosphate salt Na2HPO4 in alginate hydrogels, we can modulate their gelation time, tuning their physicochemical properties like stiffness and porosity while maintaining an appropriate injectability. Moreover, these hydrogels showed good biocompatibility when embedding a rat insulinoma cell line, especially at low Na2HPO4 concentrations, indicating that these hydrogels have potential as injectable biomaterials for Type 1 Diabetes Mellitus treatment

Force Spectroscopy Imaging and Constriction Assays Reveal the Effects of Graphene Oxide on the Mechanical Properties of Alginate Microcapsules

Microencapsulation of cells in hydrogel-based porous matrices is an approach that has demonstrated great success in regenerative cell therapy. These microcapsules work by concealing the exogenous cells and materials in a robust biomaterial that prevents their recognition by the immune system. A vast number of formulations and additives are continuously being tested to optimize cell viability and mechanical properties of the hydrogel. Determining the effects of new microcapsule additives is a lengthy process that usually requires extensive in vitro and in vivo testing. In this paper, we developed a workflow using nanoindentation (i.e., indentation with a nanoprobe in an atomic force microscope) and a custom-built microfluidic constriction device to characterize the effect of graphene oxide (GO) on three microcapsule formulations. With our workflow, we determined that GO modifies the microcapsule stiffness and surface properties in a formulation-dependent manner. Our results also suggest, for the first time, that GO alters the conformation of the microcapsule hydrogel and its interaction with subsequent coatings. Overall, our workflow can infer the effects of new additives on microcapsule surfaces. Thus, our workflow can contribute to diminishing the time required for the validation of new microcapsule formulations and accelerate their clinical translation

El Servicio de Validación de Copernicus EMS como vector de mejora de la cartografía de emergencias basada en Sentinel

[EN] The Copernicus Emergency Management Service (CEMS) is coordinated by the European Commission and “provides all actors involved in the management of natural disasters, man-made emergency situations, and humanitarian crises with timely and accurate geo-spatial information derived from satellite remote sensing and complemented by available in situ or open data sources”. It includes two components, Early Warning and Monitoring and Mapping. The latter provides on demand geo-spatial information derived from satellite imagery during all phases of the disaster management cycle. It includes 3 systems, Rapid Mapping (RM), Risk and Recovery Mapping (RRM), and a Validation Service. RM provides geospatial information immediately after a disaster to assess its impact; RRM in the prevention, preparation and reconstruction phases; and the Validation Service is in charge of validating and verifying the products generated by both, and of collecting and analyzing users’ feedback. The wide spectrum of activities framed in the Validation Service has allowed it to become a vector to improve the Mapping component through the testing of new methodologies, data input type, or approach for the creation of emergency cartography in the frame of the CEMS. The present paper introduces the main investigation lines based on Sentinel-1 and 2 for flood and fire monitoring that could be implemented in the CEMS services taking into consideration the characteristics of the Mapping component in terms of products to create and time constraints. The applicability of Sentinel-1 for flood monitoring based on the backscattering, the MultiTemporal Coherence (MTC), and dual polarization; and for burnt area delineation based on MTC was studied, while Sentinel-2 was used for burnt area delineation based on vegetation indices. Results indicate that proposed methodologies might be appropriate for the creation of crisis information products in large areas, due to the relative easy and fast implementation compared to classic photo interpretation, although further applicability analyses should be carried out.[ES] El Servicio de Gestión de Emergencias de Copernicus (CEMS), está coordinado por la Comisión Europea y “provee de información geoespacial precisa y oportuna derivada de la teledetección satelital y completada por fuentes de datos disponibles in situ o abiertas a todos los actores involucrados en la gestión de emergencias, bien sean derivadas de desastres naturales o producidos por el hombre, o de crisis humanitarias”. El servicio tiene dos componentes, uno de alerta temprana y monitoreo y otro de creación de mapas. El servicio de mapeo se encarga de proveer, bajo demanda, a los diferentes agentes de emergencias de información geoespacial derivada de imágenes de satélite en todas las fases de la gestión de emergencias, consta de 3 sistemas, Rapid Mapping (RM), Risk and Recovery Mapping (RRM), y Validation. RM aporta información inmediatamente después de un desastre para evaluar su impacto; RRM en las fases de prevención, preparación y reconstrucción; y la Validación se encarga de validar y verificar los productos generados por ambos, y de recoger y analizar los comentarios de los usuarios. El amplio espectro de actividades enmarcadas en él le ha permitido ser vector de mejora de los servicios de mapeo de emergencias mediante el testeo de nuevas metodologías, tipos de datos, o enfoques para la creación de cartografías de emergencias en el marco de CEMS. El presente artículo describe las principales líneas de investigación en el uso de datos Sentinel-1 y 2 para la monitorización de inundaciones e incendios, que se podrían implementar en el futuro en el marco de CEMS. La aplicabilidad de Sentinel-1 para el monitoreo de inundaciones basado en la retrodispersión, la coherencia multitemporal (MTC) y la polarización dual; y se estudió la delimitación del área quemada basada en MTC. Sentinel-2 se usó para delimitar áreas quemadas en base a índices de vegetación. Los resultados indican que las metodologías propuestas podrían ser apropiadas para la creación de productos de información de crisis en grandes áreas, debido a la implementación relativamente fácil y rápida en comparación con la fotointerpretación clásica, aunque deberían realizarse más análisis para su aplicación en el marco de CEMS.The authors gratefully acknowledge the contribution of Massimiliano Rossi and Antigoni Maistrali for the preparation of the materials analysed in this work.Donezar-Hoyos, U.; Albizua-Huarte, L.; Amezketa-Lizarraga, E.; Barinagarrementeria-Arrese, I.; Ciriza, R.; De Blas-Corral, T.; Larrañaga-Urien, A.... (2020). The Copernicus EMS Validation service as a vector for improving the emergency mapping based on Sentinel data. Revista de Teledetección. 0(56):23-34. https://doi.org/10.4995/raet.2020.13770OJS233405

Optical tweezers in a dusty universe: Modeling optical forces for space tweezers applications

Optical tweezers are powerful tools based on focused laser beams. They are able to trap, manipulate, and investigate a wide range of microscopic and nanoscopic particles in different media, such as liquids, air, and vacuum. Key applications of this contactless technique have been developed in many fields. Despite this progress, optical trapping applications to planetary exploration are still to be developed. Here we describe how optical tweezers can be used to trap and characterize extraterrestrial particulate matter. In particular, we exploit light scattering theory in the T-matrix formalism to calculate radiation pressure and optical trapping properties of a variety of complex particles of astrophysical interest. Our results open perspectives in the investigation of extraterrestrial particles on our planet, in controlled laboratory experiments, aiming for space tweezers applications: optical tweezers used to trap and characterize dust particles in space or on planetary bodies surface

Reduced progesterone metabolites protect rat hippocampal neurones from kainic acid excitotoxicity in vivo

The ovarian hormone progesterone is neuroprotective in some animal models of neurodegeneration. Progesterone actions in the brain may partly be mediated by the locally produced metabolites 5α-dihydroprogesterone and 3α,5α-tetrahydroprogesterone. The neuroprotective effects of these two metabolites of progesterone were assessed in this study. Ovariectomized Wistar rats were injected with kainic acid, to induce excitotoxic neuronal death in the hippocampus, and with different doses of 5α-dihydroprogesterone and 3α,5α-tetrahydroprogesterone. The number of surviving neurones in the hilus of the dentate gyrus of the hippocampus was assessed with the optical dlisector method. The administration of kainic acid resulted in a significant decrease in the number of hilar neurones and in the induction of vimentin expression in reactive astrocytes, a sign of neural damage. Low doses of 5α-dihydroprogesterone (0.25 and 0.5 mg/kg body weight, b.w.) prevented the loss of hilar neurones and the appearance of vimentin immunoreactivity in astrocytes. Higher doses (1-2 mg/kg b.w.) were not neuroprotective. By contrast, low doses of 3α,5α-tetrahydroprogesterone (0.25-1 mg/kg b.w.) were unable to protect the hilus from kainic acid while higher doses (2-4 mg/kg b.w.) were protective. The different optimal neuroprotective doses of 5α-dihydroprogesterone and 3α, 5α-tetrahydroprogesterone suggest that these two steroids may protect neurones using different mechanisms. The neuroprotective effects of 3α, 5α-tetrahydroprogesterone may be exerted by the inhibition of neuronal activity via the GABAA receptor. This latter possibility is supported by the observation that 3β,5α-tetrahydroprogesterone, an isomer of 3α,5α-tetrahydroprogesterone that does not bind to GABAA receptor, was not neuroprotective. In summary, our findings suggest that progesterone neuroprotective effects may be, at least in part, mediated by its reduced metabolites 5α-dihydroprogesterone and 3α,5α-tetrahydroprogesterone.Peer Reviewe

Selective estrogen receptor modulators protect hippocampal neurons from kainic acid excitotoxicity: Differences with the effect of estradiol

Neuroprotective effects of estradiol are well characterized in animal experimental models. However, in humans, the outcome of estrogen treatment for cognitive function and neurological diseases is very controversial. Selective estrogen receptor modulators (SERMs) may represent an alternative to estrogen for the treatment or the prevention of neurodegenerative disorders. SERMs interact with the estrogen receptors and have tissue-specific effects distinct from those of estradiol, acting as estrogen agonists in some tissues and as antagonists in others. In this study we have assessed the effect of tamoxifen, raloxifene, lasofoxifene (CP-336,156), bazedoxifeoe (TSE-424), and 17β-estradiol on the hippocampus of adult ovariectomized rats, after the administration of the excitotoxin kainic acid. Administration of kainic acid induced the expression of vimentin in reactive astroglia and a significant neuronal loss in the hilus. SERMs did not affect vimentin immunoreactivity in the hitas, while 17β-estradiol significantly reduced the surface density of vimentin immunoreactive profiles. Estradiol, tamoxifen (0.4-2 mg/kg), raloxifene (0.4-2 mg/kg), and bazedoxifene (2 mg/kg) prevented neuronal loss in the hilus after the administration of kainic acid. Lasofoxifene (0.4-2 mg/kg) was not neuroprotective. These findings indicate that SERMs present different dose-dependent neuroprotective effects. Furthermore, the mechanisms of neuroprotection by SERMs and estradiol are not identical, because SERMs do not significantly affect reactive gliosis while neuroprotection by estradiol is associated with a strong down-regulation of reactive astroglia. © 2004 Wiley Periodicals, Inc.Peer Reviewe

Reduced metabolites mediate neuroprotective effects of progesterone in the adult rat hippocampus. The synthetic progestin medroxyprogesterone acetate (Provera) is not neuroprotective

The ovarian hormone progesterone is neuroprotective in different experimental models of neurodegeneration. In the nervous system, progesterone is metabolized to 5α-dihydroprogesterone (DHP) by the enzyme 5α-reductase. DHP is subsequently reduced to 3α,5α- tetrahydroprogesterone (THP) by a reversible reaction catalyzed by the enzyme 3α-hydroxysteroid dehydrogenase. In this study we have analyzed whether progesterone metabolism is involved in the neuroprotective effect of the hormone in the hilus of the hippocampus of ovariectomized rats injected with kainic acid, an experimental model of excitotoxic cell death. Progesterone increased the levels of DHP and THP in plasma and hippocampus and prevented kainic-acid-induced neuronal loss. In contrast to progesterone, the synthetic progestin medroxyprogesterone acetate (MPA, Provera) did not increase DHP and THP levels and did not prevent kainic-acid-induced neuronal loss. The administration of the 5α-reductase inhibitor finasteride prevented the increase in the levels of DHP and THP in plasma and hippocampus as a result of progesterone administration and abolished the neuroprotective effect of progesterone. Both DHP and THP were neuroprotective against kainic acid. However, the administration of indomethacin, a 3α-hydroxysteroid dehydrogenase inhibitor, blocked the neuroprotective effect of both DHP and THP, suggesting that both metabolites are necessary for the neuroprotective effect of progesterone. In conclusion, our findings indicate that progesterone is neuroprotective against kainic acid excitotoxicity in vivo while the synthetic progestin MPA is not and suggest that progesterone metabolism to its reduced derivatives DHP and THP is necessary for the neuroprotective effect of the hormone. © 2006 Wiley Periodicals, Inc.Peer Reviewe

Antisense oligodeoxynucleotides for estrogen receptor-β and α attenuate estradiol's modulation of affective and sexual behavior, respectively

Estradiol (E2) modulates affective and socio-sexual behavior of female rodents. E2's functional effects may involve actions through α and β isoforms of estrogen receptor (ERs). The importance of E 2's actions at these isoforms for anxiety (open field, elevated plus maze), depression (forced swim test), and sexual behavior (lordosis) was investigated using an antisense oligonucleotide (AS-ODN) strategy. If ERβ is required for anti-anxiety and antidepressant-like effects, and ERα is required for sexual receptivity, of E2, then intracerebroventricular administration of AS-ODNs against these ERs should attenuate these effects and reduce immunoreactivity of ERs in brain regions that mediate these behaviors, such as the hippocampus and ventral medial hypothalamus (VMH). Ovariectomized rats were primed with 17β-E2 (10 μg) 48 h before testing (hour 0). At hours 0, 24, and 47.5, rats were infused with saline vehicle, scrambled control AS-ODNs, or AS-ODNs targeted against ERα and/or ERβ, and were tested at hour 48. Rats infused with ERβ AS-ODNs, alone, or with ERα AS-ODNs had significantly decreased open field central entries, decreased plus maze open arm time and entries, increased time spent immobile, and decreased time spent swimming in the forced swim test, and decreased ERβ immunoreactivity in the brain than did rats administered ERα AS-ODNs, vehicle, or scrambled AS-ODNs. Rats that were administered ERα AS-ODNs, alone, or with ERβ AS-ODNs had significantly decreased lordosis and decreased ERα immunoreactivity in the brain compared to rats administered ERβ AS-ODNs, vehicle, or scrambled AS-ODNs. Thus, ERβ and ERα may be required for E2's modulation of affective and sexual behavior, respectively. © 2008 Nature Publishing Group All rights reserved.Peer Reviewe

Space flight affects magnocellular supraoptic neurons of young prepuberal rats: Transient and permanent effects

Effects of microgravity on postural control and volume of extracellular fluids as well as stress associated with space flight may affect the function of hypothalamic neurosecretory neurons. Since environmental modifications in young animals may result in permanent alterations in neuroendocrine function, the present study was designed to determine the effect of a space flight on oxytocinergic and vasopressinergic magnocellular hypothalamic neurons of prepuberal rats. Fifteen-day-old Sprague-Dawley female rats were flown aboard the Space Shuttle Columbia (STS-90, Neurolab mission, experiment 150) for 16 days. Age-matched litters remained on the ground in cages similar to those of the flight animals. Six animals from each group were killed on the day of landing and eight animals from each group were maintained under standard vivarium conditions and killed 18 weeks after landing. Several signs of enhanced transcriptional and biosynthetic activity were observed in magnocellular supraoptic neurons of flight animals on the day of landing compared to control animals. These include increased c-Fos expression, larger nucleoli and cytoplasm, and higher volume occupied in the neuronal perikaryon by mitochondriae, endoplasmic reticulum, Golgi apparatus, lysosomes and cytoplasmic inclusions known as nematosomes. In contrast, the volume occupied by neurosecretory vesicles in the supraoptic neuronal perikarya was significantly decreased in flight rats. This decrease was associated with a significant decrease in oxytocin and vasopressin immunoreactive levels, suggestive of an increased hormonal release. Vasopressin levels, cytoplasmic volume and c-Fos expression returned to control levels by 18 weeks after landing. These reversible effects were probably associated to osmotic stimuli resulting from modifications in the volume and distribution of extracellular fluids and plasma during flight and landing. However, oxytocin levels were still reduced at 18 weeks after landing in flight animals compared to controls. This indicates that space flight during prepuberal age may induce irreversible modifications in the regulation of oxytocinergic neurons, which in turn may result in permanent endocrine and behavioral impairments. © 2001 Elsevier Science B.V. All rights reserved.Peer Reviewe