Habitability: CAMELOT 4

During 1988 to 1989 the NASA/USRA Advanced Design Program sponsored research and design efforts aimed at developing habitability criteria and at defining a habitability concept as a useful tool in understanding and evaluating dwellings for prolonged stays in extraterrestrial space. The Circulating Auto sufficient Mars-Earth Luxurious Orbital Transport (CAMELOT) was studied as a case in which the students would try to enhance the quality of life of the inhabitants by applying architectural design methodology. The study proposed 14 habitability criteria considered necessary to fulfill the defined habitability concept, which is that state of equilibrium that results from the interaction between components of the Individual Architecture Mission Complex, which allows a person to sustain physiological homeostatis, adequate performance, and acceptable social relationships. Architecture, design development, refinements and revisions to improve the quality of life, new insights on artificial gravity, form and constitution problems, and the final design concept are covered

Genetic landscape of 6089 inherited retinal dystrophies affected cases in Spain and their therapeutic and extended epidemiological implications

Inherited retinal diseases (IRDs), defined by dysfunction or progressive loss of photoreceptors, are disorders characterized by elevated heterogeneity, both at the clinical and genetic levels. Our main goal was to address the genetic landscape of IRD in the largest cohort of Spanish patients reported to date. A retrospective hospital-based cross-sectional study was carried out on 6089 IRD affected individuals (from 4403 unrelated families), referred for genetic testing from all the Spanish autonomous communities. Clinical, demographic and familiar data were collected from each patient, including family pedigree, age of appearance of visual symptoms, presence of any systemic findings and geographical origin. Genetic studies were performed to the 3951 families with available DNA using different molecular techniques. Overall, 53.2% (2100/3951) of the studied families were genetically characterized, and 1549 different likely causative variants in 142 genes were identified. The most common phenotype encountered is retinitis pigmentosa (RP) (55.6% of families, 2447/4403). The most recurrently mutated genes were PRPH2, ABCA4 and RS1 in autosomal dominant (AD), autosomal recessive (AR) and X-linked (XL) NON-RP cases, respectively; RHO, USH2A and RPGR in AD, AR and XL for non-syndromic RP; and USH2A and MYO7A in syndromic IRD. Pathogenic variants c.3386G > T (p.Arg1129Leu) in ABCA4 and c.2276G > T (p.Cys759Phe) in USH2A were the most frequent variants identified. Our study provides the general landscape for IRD in Spain, reporting the largest cohort ever presented. Our results have important implications for genetic diagnosis, counselling and new therapeutic strategies to both the Spanish population and other related populations.This work was supported by the Instituto de Salud Carlos III (ISCIII) of the Spanish Ministry of Health (FIS; PI16/00425 and PI19/00321), Centro de Investigación Biomédica en Red Enfermedades Raras (CIBERER, 06/07/0036), IIS-FJD BioBank (PT13/0010/0012), Comunidad de Madrid (CAM, RAREGenomics Project, B2017/BMD-3721), European Regional Development Fund (FEDER), the Organización Nacional de Ciegos Españoles (ONCE), Fundación Ramón Areces, Fundación Conchita Rábago and the University Chair UAM-IIS-FJD of Genomic Medicine. Irene Perea-Romero is supported by a PhD fellowship from the predoctoral Program from ISCIII (FI17/00192). Ionut F. Iancu is supported by a grant from the Comunidad de Madrid (CAM, PEJ-2017-AI/BMD7256). Marta del Pozo-Valero is supported by a PhD grant from the Fundación Conchita Rábago. Berta Almoguera is supported by a Juan Rodes program from ISCIII (JR17/00020). Pablo Minguez is supported by a Miguel Servet program from ISCIII (CP16/00116). Marta Corton is supported by a Miguel Servet program from ISCIII (CPII17/00006). The funders played no role in study design, data collection, data analysis, manuscript preparation and/or publication decisions

A two-step target binding and selectivity support vector machines approach for virtual screening of dopamine receptor subtype-selective ligands

10.1371/journal.pone.0039076PLoS ONE76

CARMENES: high-resolution spectra and precise radial velocities in the red and infrared

SPIE Astronomical Telescopes + Instrumentation (2018, Austin, Texas, United States

A giant exoplanet orbiting a very-low-mass star challenges planet formation models

Surveys have shown that super-Earth and Neptune-mass exoplanets are more frequent than gas giants around low-mass stars, as predicted by the core accretion theory of planet formation. We report the discovery of a giant planet around the very-low-mass star GJ 3512, as determined by optical and near-infrared radial-velocity observations. The planet has a minimum mass of 0.46 Jupiter masses, very high for such a small host star, and an eccentric 204-day orbit. Dynamical models show that the high eccentricity is most likely due to planet-planet interactions. We use simulations to demonstrate that the GJ 3512 planetary system challenges generally accepted formation theories, and that it puts constraints on the planet accretion and migration rates. Disk instabilities may be more efficient in forming planets than previously thought

Insulin-like growth factor I is required for vessel remodeling in the adult brain

Although vascular dysfunction is a major suspect in the etiology of several important neurodegenerative diseases, the signals involved in vessel homeostasis in the brain are still poorly understood. We have determined whether insulin-like growth factor I (IGF-I), a wide-spectrum growth factor with angiogenic actions, participates in vascular remodeling in the adult brain. IGF-I induces the growth of cultured brain endothelial cells through hypoxiainducible factor 1α and vascular endothelial growth factor, a canonical angiogenic pathway. Furthermore, the systemic injection of IGF-I in adult mice increases brain vessel density. Physical exercise that stimulates widespread brain vessel growth in normal mice fails to do so in mice with low serum IGF-I. Brain injury that stimulates angiogenesis at the injury site also requires IGF-I to promote perilesion vessel growth, because blockade of IGF-I input by an anti-IGF-I abrogates vascular growth at the injury site. Thus, IGF-I participates in vessel remodeling in the adult brain. Low serum/brain IGF-I levels that are associated with old age and with several neurodegenerative diseases may be related to an increased risk of vascular dysfunction

Biomaterial to promote nerve regeneration: towards clinical trials

The peripheral nervous system (PNS) can regener- ate after injury but to fill a gap it needs to find a proper guide directing the axonal elongation. Many techni- ques and devices have been studied in order to pro- mote nerve regeneration but are still inadequate. The aim of this work is to validate an innovative high poros- ity collagen tube (medical devices, MD) in order to induce nerve regeneration in a 10-mm gap in the adult rat sciatic nerve. Nerves were retrieved for morpholog- ical and ultrastructural analysis at 8, 15, 30, 40 and 54, 90 and 120 days postoperatively and analyzed at differ- ent levels. Nerve conduction studies were also evalu- ated. At 8 days postoperatively fibroblast activation and extracellular matrix reorganization were already evident associated with a great number of mature endoneurial neovessels with tight junctions. In the fol- lowing time points an active process of axonal regen- eration was documented; after two months we showed, in the regenerated mid-graft, a normal num- ber of well myelinated axons with normal G-ratio and definite signs of reinnervation in the tibial and peroneal branch. No inflammatory cells were evident. Electro- physiological assessment showed a motor action potential at 90 days postoperatively distally, recordable at the paw. Overall, the neurophysiological and neuro- pathological data demonstrate the terrific quality of nerve regeneration using our MD which performs bet- ter in comparison to the collagen already available in clinical practice and the silicone tubes, used as a con- trol. These results make us confident in proposing our MD in clinical practice to treat injury of the PNS

High porosity collagen tube: an innovative medical device for nerve regeneration

Bridging the gap after a nerve transection has always been a top challenge in the field of neuroscience. The peripheral nervous system can regenerate after injury but to fill a gap needs to find a proper guide directing the axonal elongation. Many techniques and devices have been studied in order to promote nerve regeneration but are still inade- quate. The aim of this work is validating an innovative high porosity collagen tube (medical devices, MD) and comparing the nerve outgrowth through this MD to the already avail- able in clinical practice NeuroGen IntegraÒ collagen and the silicone tubes, as a standard control, in an animal model of traumatic injury. The conduits were implanted in a 10 mm- gap in rat sciatic nerve and retrieved at different time points for morphological and ultrastructural analysis. Nerve conduc- tion studies were also evaluated. Nerve outgrowth through the NeuroGen IntegraÒ devices appeared to be similar to the one in the silicone tubes, being characterized by mini- fascicles containing less small axons with thin myelin and without a well-organized blood vessels distribution in the en- doneurium. In contrast, our MD showed, in the regenerated mid-graft, a normal size and number of nerve fibers with a normal myelination (G-ratio), already evident at 60 days postoperatively. Moreover, perineurium and blood vessels appeared absolutely normal with tight junction by EM. At 90 days postoperatively a nerve action potential was recordable distally, at the paw, in the sciatic nerves of the rats implanted with our MD or with the NeuroGen ones whereas was absent in the silicon group. Overall the neurophysiologi- cal and neuropathological data demonstrate the terrific qual- ity of nerve regeneration using our MD. These results make us confident in proposing our MD in the clinical practice to treat injury of the PNS

Optimal micro-patterning of a collagen scaffold coordinates the induction of morphogenetic pathways in adult nerve regeneration

Introduction Nerve injury is a frequent event especially after traumatic lesion, affecting mainly young people. Various therapeutic approaches have been proposed for patients suffering from peripheral nerve injuries. Despite the significant increase in the understanding of the pathophysiology of nerve, results have been, so far, inconsistent, in terms of both quality as well as extent of nerve regeneration and re-innervation. The use of a conduit to reconnect the proximal and distal stumps of a transected nerve and induce peripheral nervous system (PNS) regeneration has been the subject of a large number of investigations. While it is quite established that the presence of a conduit between the transected stumps allows PNS regeneration [1], the micro-structural, mechanical and compositional features of the conduit, as any material inserted within, might significantly affect the quality of regeneration [2, 3]. We have previously developed a micro-patterned collagen scaffold (MPCS), by a spinning technique [4], with a peculiar radially aligned porosity of the tube wall, and predicted that its microstructure might play a significant role in the regulation of cellular and molecular mechanisms sustaining cell behaviour inside the scaffold and, in turn, improving distal induced regeneration. In this work the clinico-pathological impact of this MPCS was evaluated in the adult rat sciatic nerve. Neurophysiological, morphological and whole genome expression studies were conducted to assess the major pathways regulating nerve development and morphogenesis. Materials & Methods A complete and detailed description of the process adopted to produce MPCS has been reported [4]. Scaffolds are prepared using a collagen-based slurry; spinning of the slurry in a proper apparatus and rapid freezing of the sedimented suspension in liquid nitrogen; freeze-drying of the solidified suspension to obtain the final MPCS. Nerve regeneration in MPCS-implanted transected rats was evaluated in vivo over a 10-mm critical size defect in the adult rat sciatic nerve. Rats with transection of the sciatic nerve and implanted with either commercial collagen (NeuraGen®) or silicon conduits were used as controls. To evaluate the degree of regeneration and re-myelination after nerve transection, neurophysiological and morphological studies were performed. Together with sciatic nerves, the tibial plantar nerves at the paw were also investigated, to establish the process of re-innervation at the distal part. Whole gene expression (GE) profiling studies on injured sciatic nerve rats were conducted to investigate the molecular changes and the regulation of biological processes provided by our MPCS. Results & Discussion A damage, which determines a detachment of two nerve stumps, like a traumatic lesion, needs a device that creates an ideal micro-environment in order to facilitate axonal regeneration and re-myelination. Thus, we have developed a MPCS under the hypothesis that the micro-structure of the wall conduit could create a favourable micro-environment for full nerve regeneration after experimental transection. Neurophysiological and morphological studies suggested a faster functional nerve recovery of MPCS-implanted rats compared to rats treated with other conduits, as well as a prompt restoration of a functional vasculature with a physiological blood-nerve barrier. Moreover, in the MPCS, the long-term analysis showed a normal development of nerve, consisting of normal axon diameters and myelin thickness. Up-regulation of the myelin specific-gene observed at early time only on MPCS suggested the ability of our scaffold in providing clues for Schwann cell differentiation. Whole genome gene expression analyses further confirmed that the MPCS induces selective gene expression patterns and enhanced cells proliferation, motility and myelination. Conclusion Our findings provide remarkable molecular and ultra-structural evidence that the optimal micro-patterning of the proposed collagen scaffold plays a key role in turning the inner micro-environment into hospitable for development, rather than induced regeneration, of the proximal nerve stump. Within these optimal conditions, the transected nerve recapitulates in a coordinated fashion its innate programs of differentiation, which ultimately lead to progressive substitution of non-neuronal with neuronal tissues. We hypothesize that the radially aligned porosity of the MPCS promotes nerve regeneration by inducing morphogenetic stimuli and orchestrating cell behaviour towards a physiological regeneration mode