A comprehensive human minimal gut metagenome extends the host’s metabolic potential

Accumulating evidence suggests that humans could be considered as holobionts in which the gut microbiota play essential functions. Initial metagenomic studies reported a pattern of shared genes in the gut microbiome of different individuals, leading to the definition of the minimal gut metagenome as the set of microbial genes necessary for homeostasis and present in all healthy individuals. This study analyses the minimal gut metagenome of the most comprehensive dataset available, including individuals from agriculturalist and industrialist societies, also embodying highly diverse ethnic and geographical backgrounds. The outcome, based on metagenomic predictions for community composition data, resulted in a minimal metagenome comprising 3412 genes, mapping to 1856 reactions and 128 metabolic pathways predicted to occur across all individuals. These results were substantiated by the analysis of two additional datasets describing the microbial community compositions of larger Western cohorts, as well as a substantial shotgun metagenomics dataset. Subsequent analyses showed the plausible metabolic complementarity provided by the minimal gut metagenome to the human genomeThis work was funded by the Spanish Ministry of Science and Innovation, grant numbers BIO2016-80101-R and PID2019-108797RB-I0

Hand-developed creative prototyping. Methodological proposal and experimentation

The generation of original and innovative ideas is a challenge for any professional. There are several studies that demonstrate how the capacity to explore creativity is reduced until reaching educational levels where it is hardly experienced, and for this reason it is necessary to introduce it in the classroom to complement their academic training before their incorporation into the labour market. The use of new technologies implies in turn an abandonment of manual or craft skills, losing in this area a very relevant possibility of creative development. Most of the methods that are usually used to generate ideas are related to oral and written conceptualization, but manual ideation is practically not contemplated. This study proposes a methodology for generating ideas based on traditional ideation from the physical creation of models as part of the creative process. This methodology has been used with satisfactory results in 38 courses at the Industrial Organisation School (Spain), with 382 people between 18 and 30 years of age participating in the study, demonstrating that the development of creative skills obtained through this new approach can have a very significant impact on students' later career development.This research did not receive any specific grant from funding agencies in the public, commercial or not-for-profit sectors

Análisis de conectividad y densidad de la red vial en la Reserva Natural del Iberá con Sistemas de Información Geográfica (SIG)

Desde el punto de vista del sistema de transporte la red es un elemento fundamental a la hora de explicar cómo funciona un determinado territorio. En este sentido, la Geografía ha incorporado de manera efectiva diferentes técnicas cuantitativas y los Sistemas de Información Geográfica, para analizar los desequilibrios espaciales. El área de la Reserva Natural de los Esteros del Iberá tiene escasa información referida a sus características humanas, y en lo particular referido a la infraestructura vial. Por esa razón, este trabajo pretender ser un aporte al conocimiento de las características estructurales de la red de transporte interna en la Reserva. Es por ello que, se pretende conocer el grado de conectividad de la red vial en la Reserva mediante el cálculo de índices propios de la Teoría de Grafos, además de identificar patrones espaciales en la distribución de la infraestructura vial. La secuencia metodológica sobre la cual se organizó el trabajo comprendió la: a) recopilación de información cartográfica, estadística y documental, b) consulta a fuentes claves de la temática como el Instituto Geográfico Nacional, la Dirección Provincial de Vialidad de Corrientes, etc. c) relevamiento e inventario de la red de transporte por digitalización c) cálculo de variables como longitud de red interior, densidad Kernel, e índices Alfa y Gamma, d) elaboración de cartografía y cuadros estadísticos, g) interpretación de la información resultante. Los resultados indican que el área de la Reserva presenta una red vial con baja densidad y conectividad producto de una distribución heterogénea sobre el espacio. Esta cuestión se mantiene en las dos fuentes de información analizadas, aunque presentan diferentes participaciones en los departamento

Geometric modelling of the human cornea: A new approach for the study of corneal ectatic disease. A pilot investigation

The aim of this study was to describe the application of a new bioengineering graphical technique based on geometric custom modelling capable to detect and to discriminate small variations in the morphology of the corneal surface. A virtual 3D solid custom model of the cornea was obtained employing Computer Aided Geometric Design tools, using raw data from a discrete and finite set of spatial points representative of both sides of the corneal surface provided by a corneal topographer. Geometric reconstruction was performed using B-Spline functions, defining and calculating the representative geometric variables of the corneal morphology of patients under clinical diagnosis of keratoconus

An update to Hippocampome.org by integrating single-cell phenotypes with circuit function in vivo

Understanding brain operation demands linking basic behavioral traits to cell-type specific dynamics of different brain-wide subcircuits. This requires a system to classify the basic operational modes of neurons and circuits. Single-cell phenotyping of firing behavior during ongoing oscillations in vivo has provided a large body of evidence on entorhinal-hippocampal function, but data are dispersed and diverse. Here, we mined literature to search for information regarding the phase-timing dynamics of over 100 hippocampal/entorhinal neuron types defined in . We identified missing and unresolved pieces of knowledge (e.g., the preferred theta phase for a specific neuron type) and complemented the dataset with our own new data. By confronting the effect of brain state and recording methods, we highlight the equivalences and differences across conditions and offer a number of novel observations. We show how a heuristic approach based on oscillatory features of morphologically identified neurons can aid in classifying extracellular recordings of single cells and discuss future opportunities and challenges towards integrating single-cell phenotypes with circuit function.Peer reviewe

Efecto de los fílleres activos en la resistencia al envejecimiento de las mezclas asfálticas mediante el uso del ensayo Fénix

Se presentan los resultados de investigaciones realizadas para tratar de esclarecer los beneficios que otorga la incorporación de fílleres activos a las mezclas asfálticas en caliente, en particular los derivados del incremento de la resistencia al envejecimiento del mástico y los consecuentes efectos sobre propiedades funcionales y mecánicas de las mezclas después de un cierto período de servicio. Se empleó para estas experiencias de simulación una mezcla patrón con los mismos agregados pétreos y ligante bituminoso pero variando el tipo y porcentaje de fíller de aporte (cal, carbonato de calcio o una composición de ambos). La metodología de análisis fue el Ensayo Fénix, que evalúa los fallos por fisuración a partir de parámetros representativos, sometiendo las probetas elaboradas a distintos tiempos de envejecimiento acelerado en laboratorio y ensayándolas a temperaturas medias y bajas. De los resultados logrados se obtienen, mediante un análisis cuali-cuantitativo de los indicadores puestos en juego, conclusiones valiosas acerca de la acción protectora de los fílleres activos ante los mecanismos que rigen el fallo por fisuras en mezclas asfálticas envejecidas, puntualizándose las diferencias encontradas al emplear diferentes proporciones de los fílleres de aporte incorporados. Finalmente, se emiten una serie de recomendaciones a la hora de especificar el tipo y proporción de fíller a agregar a las mezclas asfálticas en caliente a fin de optimizar su respuesta funcional en los pavimentos envejecidos.Postprint (published version

Structural plasticity in I-Ag7 links autoreactivity to hybrid insulin peptides in type I diabetes

We recently provided evidence for promiscuous recognition of several different hybrid insulin peptides (HIPs) by the highly diabetogenic, I-Ag7-restricted 4.1-T cell receptor (TCR). To understand the structural determinants of this phenomenon, we solved the structure of an agonistic HIP/I-Ag7 complex, both in isolation as well as bound to the 4.1-TCR. We find that HIP promiscuity of the 4.1-TCR is dictated, on the one hand, by an amino acid sequence pattern that ensures I-Ag7 binding and, on the other hand, by the presence of three acidic residues at positions P5, P7 and P8 that favor an optimal engagement by the 4.1-TCR’s complementary determining regions. Surprisingly, comparison of the TCR-bound and unbound HIP/I-Ag7 structures reveals that 4.1-TCR binding triggers several novel and unique structural motions in both the I-Ag7 molecule and the peptide that are essential for docking. This observation indicates that the type 1 diabetes-associated I-Ag7 molecule is structurally malleable and that this plasticity allows the recognition of multiple peptides by individual TCRs that would otherwise be unable to do so

Transcriptional re-programming of insulin B-chain epitope-specific T-follicular helper cells into anti-diabetogenic T-regulatory type-1 cells

Systemic delivery of nanoparticles (NPs) coated with mono-specific autoimmune disease-relevant peptide-major histocompatibility complex class II (pMHCII) molecules can resolve organ inflammation in various disease models in a disease-specific manner without impairing normal immunity. These compounds invariably trigger the formation and systemic expansion of cognate pMHCII-specific T-regulatory type 1 (TR1) cells. By focusing on type 1 diabetes (T1D)-relevant pMHCII-NP types that display an epitope from the insulin B-chain bound to the same MHCII molecule (IAg7) on three different registers, we show that pMHCII-NP-induced TR1 cells invariably co-exist with cognate T-Follicular Helper (TFH)-like cells of quasi-identical clonotypic composition and are oligoclonal, yet transcriptionally homogeneous. Furthermore, these three different TR1 specificities have similar diabetes reversal properties in vivo despite being uniquely reactive against the peptide MHCII-binding register displayed on the NPs. Thus, pMHCII-NP treatment using nanomedicines displaying different epitope specificities results in the simultaneous differentiation of multiple antigen-specific TFH-like cell clones into TR1-like cells that inherit the fine antigenic specificity of their precursors while acquiring a defined transcriptional immunoregulatory program

CPEB alteration and aberrant transcriptome-polyadenylation lead to a treatable SLC19A3 deficiency in Huntington's disease

Huntington’s disease (HD) is a hereditary neurodegenerative disorder of the basal ganglia for which disease-modifying treatments are not yet available. Although gene-silencing therapies are currently being tested, further molecular mechanisms must be explored to identify druggable targets for HD. Cytoplasmic polyadenylation element binding proteins 1 to 4 (CPEB1 to CPEB4) are RNA binding proteins that repress or activate translation of CPE-containing transcripts by shortening or elongating their poly(A) tail. Here, we found increased CPEB1 and decreased CPEB4 protein in the striatum of patients and mouse models with HD. This correlated with a reprogramming of polyadenylation in 17.3% of the transcriptome, markedly affecting neurodegeneration-associated genes including PSEN1, MAPT, SNCA, LRRK2, PINK1, DJ1, SOD1, TARDBP, FUS, and HTT and suggesting a new molecular mechanism in neurodegenerative disease etiology. We found decreased protein content of top deadenylated transcripts, including striatal atrophy–linked genes not previously related to HD, such as KTN1 and the easily druggable SLC19A3 (the ThTr2 thiamine transporter). Mutations in SLC19A3 cause biotin-thiamine–responsive basal ganglia disease (BTBGD), a striatal disorder that can be treated with a combination of biotin and thiamine. Similar to patients with BTBGD, patients with HD demonstrated decreased thiamine in the cerebrospinal fluid. Furthermore, patients and mice with HD showed decreased striatal concentrations of thiamine pyrophosphate (TPP), the metabolically active form of thiamine. High-dose biotin and thiamine treatment prevented TPP deficiency in HD mice and attenuated the radiological, neuropathological, and motor HD-like phenotypes, revealing an easily implementable therapy that might benefit patients with HD