Bayesian Sparse Regression Analysis Documents the Diversity of Spinal Inhibitory Interneurons.

Documenting the extent of cellular diversity is a critical step in defining the functional organization of tissues and organs. To infer cell-type diversity from partial or incomplete transcription factor expression data, we devised a sparse Bayesian framework that is able to handle estimation uncertainty and can incorporate diverse cellular characteristics to optimize experimental design. Focusing on spinal V1 inhibitory interneurons, for which the spatial expression of 19 transcription factors has been mapped, we infer the existence of ~50 candidate V1 neuronal types, many of which localize in compact spatial domains in the ventral spinal cord. We have validated the existence of inferred cell types by direct experimental measurement, establishing this Bayesian framework as an effective platform for cell-type characterization in the nervous system and elsewhere.

Spinal Inhibitory Interneuron Diversity Delineates Variant Motor Microcircuits.

Animals generate movement by engaging spinal circuits that direct precise sequences of muscle contraction, but the identity and organizational logic of local interneurons that lie at the core of these circuits remain unresolved. Here, we show that V1 interneurons, a major inhibitory population that controls motor output, fractionate into highly diverse subsets on the basis of the expression of 19 transcription factors. Transcriptionally defined V1 subsets exhibit distinct physiological signatures and highly structured spatial distributions with mediolateral and dorsoventral positional biases. These positional distinctions constrain patterns of input from sensory and motor neurons and, as such, suggest that interneuron position is a determinant of microcircuit organization. Moreover, V1 diversity indicates that different inhibitory microcircuits exist for motor pools controlling hip, ankle, and foot muscles, revealing a variable circuit architecture for interneurons that control limb movement.

Genetic and epigenetic coordination of cortical interneuron development.

One of the hallmarks of the cerebral cortex is the extreme diversity of interneurons1-3. The two largest subtypes of cortical interneurons, parvalbumin- and somatostatin-positive cells, are morphologically and functionally distinct in adulthood but arise from common lineages within the medial ganglionic eminence4-11. This makes them an attractive model for studying the generation of cell diversity. Here we examine how developmental changes in transcription and chromatin structure enable these cells to acquire distinct identities in the mouse cortex. Generic interneuron features are first detected upon cell cycle exit through the opening of chromatin at distal elements. By constructing cell-type-specific gene regulatory networks, we observed that parvalbumin- and somatostatin-positive cells initiate distinct programs upon settling within the cortex. We used these networks to model the differential transcriptional requirement of a shared regulator, Mef2c, and confirmed the accuracy of our predictions through experimental loss-of-function experiments. We therefore reveal how a common molecular program diverges to enable these neuronal subtypes to acquire highly specialized properties by adulthood. Our methods provide a framework for examining the emergence of cellular diversity, as well as for quantifying and predicting the effect of candidate genes on cell-type-specific development.

MultiVI: deep generative model for the integration of multimodal data.

Jointly profiling the transcriptome, chromatin accessibility and other molecular properties of single cells offers a powerful way to study cellular diversity. Here we present MultiVI, a probabilistic model to analyze such multiomic data and leverage it to enhance single-modality datasets. MultiVI creates a joint representation that allows an analysis of all modalities included in the multiomic input data, even for cells for which one or more modalities are missing. It is available at scvi-tools.org .

Benthodytes violeta, a new species of a deep-sea holothuroid (Elasipodida: Psychropotidae) from Mar del Plata Canyon (south-western Atlantic Ocean).

A new species of elasipodid holothuroid, Benthodytes violeta sp. nov., is described from the Mar del Plata Canyon off Buenos Aires Province (around 38ºS-54ºW). It was taken at four locations at depths ranging from 1500 to 1950 m. This new species has a violet gelatinous body of up to 200 mm in length, with eight pairs of dorsal appendages, lateral festooned edges and four rows of tube feet ventrally. Body wall ossicles comprise rods and crosses with three or four arms and a central bipartite apophysis borne on the primary cross; tentacles and gonad deposits comprise rods and crosses with three and four arms. This is the first report of a holothuroid from the Mar del Plata Canyon area.

A STATISTICAL FRAMEWORK FOR THE MODELING OF THE CONTINUOUS PROGRESSION OF ALZHEIMER'S DISEASE.

Throughout an organism's life, a multitude of biological systems transition through complex biophysical processes. These processes serve as indicators of the underlying biological states. Inferring these latent unobserved states is a key problem in modern biology and neuroscience. Unfortunately, in many experimental setups we can at best obtain snapshots of the system at different times for different individuals, and one major challenge is the one of reconciling those measurements. This formalism is particularly relevant in the study of Alzheimer's Disease (AD) progression, in which we observe in brain donors the aggregation of pathological proteins but the underlying disease state is unknown. The progression of AD can be modeled by assigning a latent score - termed pseudotime - to each pathological state, creating a pseudotemporal ordering of donors based on their pathological burden. This paper proposes a hierarchical Bayesian framework to model AD progression using detailed quantification of multiple AD pathological proteins from the Seattle AD Brain Cell Atlas consortium (SEA-AD). Inspired by biophysical models, we model pathological burden as an exponential process. Theoretical properties of the model are studied, by using linearization to reveal convergence and identifiability properties. We provide Markov chain Monte Carlo estimation algorithms, and show the effectiveness of our approach with multiple simulation studies across data conditions. Applying the methodology to SEA-AD brain data, we infer pseudotime for each donor and order them by pathological burden. Finally, we analyze the information within each pathological feature and utilize it to refine the model by focusing on the most informative pathologies. This lays the groundwork for suggesting future experimental design approaches.

A new species of Havelockia Pearson, 1903 from the Argentine Sea (Holothuroidea: Dendrochirotida: Sclerodactylidae).

Havelockia pegi sp. nov., is here described from shallow waters of the Argentine Sea. This new species is distinctive in the purple colouration of its tentacles, scarcity of body wall ossicles and the presence of rosette-shaped ossicles in both the introvert and the tentacles. It is not closely related to any of its congenors. This is the first record of a true sclerodactylid from Argentina. Thandarum hernandezi Martinez & Brogger, 2012, described in the family Sclerodactylidae, is now classified in the family Sclerothyonidae.

Integrated multimodal cell atlas of Alzheimer's disease.

Alzheimer's disease (AD) is the most common cause of dementia in older adults. Neuropathological and imaging studies have demonstrated a progressive and stereotyped accumulation of protein aggregates, but the underlying molecular and cellular mechanisms driving AD progression and vulnerable cell populations affected by disease remain coarsely understood. The current study harnesses single cell and spatial genomics tools and knowledge from the BRAIN Initiative Cell Census Network to understand the impact of disease progression on middle temporal gyrus cell types. We used image-based quantitative neuropathology to place 84 donors spanning the spectrum of AD pathology along a continuous disease pseudoprogression score and multiomic technologies to profile single nuclei from each donor, mapping their transcriptomes, epigenomes, and spatial coordinates to a common cell type reference with unprecedented resolution. Temporal analysis of cell-type proportions indicated an early reduction of Somatostatin-expressing neuronal subtypes and a late decrease of supragranular intratelencephalic-projecting excitatory and Parvalbumin-expressing neurons, with increases in disease-associated microglial and astrocytic states. We found complex gene expression differences, ranging from global to cell type-specific effects. These effects showed different temporal patterns indicating diverse cellular perturbations as a function of disease progression. A subset of donors showed a particularly severe cellular and molecular phenotype, which correlated with steeper cognitive decline. We have created a freely available public resource to explore these data and to accelerate progress in AD research at SEA-AD.org.

Morphological responses of three persistent native anuran species after forest conversion into monoculture pine plantations: tolerance or prosperity?

Species loss by habitat replacement operating as an ecological filter is a well-known consequence of modern human activities. In contrast, the ecological and evolutionary response of species overcoming those filters in converted habitats has not been thoroughly explored. Species that persist are subject to novel and potentially stressful conditions that may induce certain morphological changes. We evaluated changes in the functional morphology of three anuran species persisting after the conversion of areas of the Atlantic Forest into pine plantations. We specifically evaluated differences in body size and body condition indices, head width, and hind legs' length between adult individuals from both habitats and sexes. Habitat conversion and sexual dimorphism affected the morphology of the three anurans, with varying effects upon species and traits. Regarding the effect of habitat conversion, Elachistocleis bicolor increased body condition in plantations with no changes in the other traits, Physalaemus cuvieri showed only a marginal increment in residual body mass in plantations, and Odontophrynus americanus exhibited a substantial increment in body size while maintaining its body condition in plantations. Remarkably, none of the results suggested these persistent anurans were stressed by forest conversion. This study shows that habitat conversion may induce intraspecific morphological changes in ecologically relevant traits of persistent species, and that disturbed areas do not necessarily imply stressful, low quality habitats affecting all persistent native species negatively.

Characterizing chromatin landscape from aggregate and single-cell genomic assays using flexible duration modeling.

ATAC-seq has become a leading technology for probing the chromatin landscape of single and aggregated cells. Distilling functional regions from ATAC-seq presents diverse analysis challenges. Methods commonly used to analyze chromatin accessibility datasets are adapted from algorithms designed to process different experimental technologies, disregarding the statistical and biological differences intrinsic to the ATAC-seq technology. Here, we present a Bayesian statistical approach that uses latent space models to better model accessible regions, termed ChromA. ChromA annotates chromatin landscape by integrating information from replicates, producing a consensus de-noised annotation of chromatin accessibility. ChromA can analyze single cell ATAC-seq data, correcting many biases generated by the sparse sampling inherent in single cell technologies. We validate ChromA on multiple technologies and biological systems, including mouse and human immune cells, establishing ChromA as a top performing general platform for mapping the chromatin landscape in different cellular populations from diverse experimental designs.

A New Era for Space Life Science: International Standards for Space Omics Processing.

Space agencies have announced plans for human missions to the Moon to prepare for Mars. However, the space environment presents stressors that include radiation, microgravity, and isolation. Understanding how these factors affect biology is crucial for safe and effective crewed space exploration. There is a need to develop countermeasures, to adapt plants and microbes for nutrient sources and bioregenerative life support, and to limit pathogen infection. Scientists across the world are conducting space omics experiments on model organisms and, more recently, on humans. Optimal extraction of actionable scientific discoveries from these precious datasets will only occur at the collective level with improved standardization. To address this shortcoming, we established ISSOP (International Standards for Space Omics Processing), an international consortium of scientists who aim to enhance standard guidelines between space biologists at a global level. Here we introduce our consortium and share past lessons learned and future challenges related to spaceflight omics.

Nucleotide polymorphism in the drought responsive gene Asr2 in wild populations of tomato.

The Asr gene family (named after abscicic acid [ABA], stress, ripening), exclusively present in plant genomes, is involved in transcriptional regulation. Its members are up-regulated in roots and leaves of water- or salt-stressed plants. In previous work, evidence of adaptive evolution (as inferred from synonymous and nonsynonymous divergence rates) has been reported for Asr2 in Solanum chilense and S. arcanum, two species dwelling in habitats with different precipitation regimes. In this paper we investigate patterns of intraspecific nucleotide variation in Asr2 and the unlinked locus CT114 in S. chilense and S. arcanum. The extent of nucleotide diversity in Asr2 differed between species in more than one order of magnitude. In both species we detected evidence of non-neutral evolution, which may be ascribed to different selective regimes, potentially associated to unique climatic features, or, alternatively, to demographic events. The results are discussed in the light of demographic and selective hypotheses.

Corallimorpharians (Anthozoa: Corallimorpharia) from the Argentinean Sea.

Corallimorpharians are a relative small group of anthozoan cnidarians, also known as jewel sea anemones. They resemble actiniarian sea anemones in lacking a skeleton and being solitary, but resemble scleractinian corals in external and internal morphology, and they are considered to be the sister group of the stony corals. Corynactis carnea (=Sphincteractis sanmatiensis) is a small, common and eye catching species that inhabits the shallow water of northern Patagonia and the Argentinean shelf up to 200 m depth. Corallimorphus rigidus is registered for the first time from the southwestern Atlantic Ocean. It is a rather big and rare species that inhabits only the deep sea. Only two specimens were found at 2934 m depth in Mar del Plata submarine canyon, in an area under the influence of the Malvinas current, which may explain its occurrence. These two species are the only two known jewel sea anemones in the Argentinean sea and are reported and described herein.

Origin and Segmental Diversity of Spinal Inhibitory Interneurons.

Motor output varies along the rostro-caudal axis of the tetrapod spinal cord. At limb levels, ∼60 motor pools control the alternation of flexor and extensor muscles about each joint, whereas at thoracic levels as few as 10 motor pools supply muscle groups that support posture, inspiration, and expiration. Whether such differences in motor neuron identity and muscle number are associated with segmental distinctions in interneuron diversity has not been resolved. We show that select combinations of nineteen transcription factors that specify lumbar V1 inhibitory interneurons generate subpopulations enriched at limb and thoracic levels. Specification of limb and thoracic V1 interneurons involves the Hox gene Hoxc9 independently of motor neurons. Thus, early Hox patterning of the spinal cord determines the identity of V1 interneurons and motor neurons. These studies reveal a developmental program of V1 interneuron diversity, providing insight into the organization of inhibitory interneurons associated with differential motor output.

Effect of eccentric training on mitochondrial function and oxidative stress in the skeletal muscle of rats.

The objective of the present study was to investigate the effects of eccentric training on the activity of mitochondrial respiratory chain enzymes, oxidative stress, muscle damage, and inflammation of skeletal muscle. Eighteen male mice (CF1) weighing 30-35 g were randomly divided into 3 groups (N = 6): untrained, trained eccentric running (16°; TER), and trained running (0°) (TR), and were submitted to an 8-week training program. TER increased muscle oxidative capacity (succinate dehydrogenase and complexes I and II) in a manner similar to TR, and TER did not decrease oxidative damage (xylenol and creatine phosphate) but increased antioxidant enzyme activity (superoxide dismutase and catalase) similar to TR. Muscle damage (creatine kinase) and inflammation (myeloperoxidase) were not reduced by TER. In conclusion, we suggest that TER improves mitochondrial function but does not reduce oxidative stress, muscle damage, or inflammation induced by eccentric contractions.

Tooth microstructure and feeding biology of the brittle star Ophioplocus januarii (Echinodermata: Ophiuroidea) from northern Patagonia, Argentina / Microestructura dental y biología alimentaria del Ophioplocus januarii (Echinodermata: Ophiuroidea) del norte de Patagonia, Argentina

Abstract Ophioplocus januarii is a common brittle star on soft and hard substrates along the Argentinian and Brazilian coasts. Based on stomach contents, tooth microstructure and field observations we identified its food. Opposed to previous suggestions, O. januarii appears to be a microphagous species feeding on macroalgal fragments (found in 60.0 % of the analyzed stomachs with content), plant debris (28.0 %), animal cuticle structures (13.0 %), and unidentifiable material (30.7 %). Less frequent items found were foraminiferans, ostracods, an amphipod, a juvenile bivalve, and other crustaceans. Electronic microscope revealed digested material, diatoms and small crustacean appendices. Thus, O. januarii is an omnivorous species, feeding mainly on algae, complemented opportunistically with other items. Suspension feeding was observed in the field. It has an fenestrated arrangement intermediate between the previously described uniform and compound teeth. Rev. Biol. Trop. 63 (Suppl. 2): 353-360. Epub 2015 June 01.

Resumen El ofiuroideo Ophioplocus januarii se distribuye a lo largo de las costas de Argentina y Brasil, encontrándose tanto en substratos duros como blandos. En base al análisis de contenidos estomacales y la microestructura de los dientes, junto a observaciones de campo, se describe el comportamiento alimentario de esta especie. Opuesto a suposiciones previas, O. januarii es una especie micrófaga que se alimenta de fragmentos de macroalgas (encontrados en el 60.0 % de los estómagos analizados que presentaban contenido), detritos vegetales (28.0 %), estructuras cuticulares animales (13.0 %) y material inidentificable (30.7 %). Menos frecuente, se encontraron foraminíferos, ostrácodos, un anfípodo, un bivalvo juvenil y otros crustáceos. Pequeñas porciones del material inidentificable fueron analizadas en el microscopio electrónico de barrido, resultando ser material digerido, diatomeas y pequeños apéndices de crustáceos. Así, O. januarii es una especie omnívora, que se alimenta principalmente de algas, complementando su dieta de manera oportunista con otros ítems. Las observaciones de campo revelaron alimentación suspensívora. El análisis de la microestructura del estereoma del diente resultó en un arreglo del tipo fenestrado intermedio, que se encuentra entre los dos tipos de arreglos descriptos hasta ahora, los dientes de tipo uniforme y los compuestos. De estos últimos, el primero ha sido encontrado en especies macrófagas mientras que el segundo se corresponde a ofiuroideos micrófagos. En el presente trabajo, se propone la existencia de un nuevo tipo de arreglo intermedio en la matriz dental de los ofiuroideos.

Effect of eccentric training on mitochondrial function and oxidative stress in the skeletal muscle of rats

The objective of the present study was to investigate the effects of eccentric training on the activity of mitochondrial respiratory chain enzymes, oxidative stress, muscle damage, and inflammation of skeletal muscle. Eighteen male mice (CF1) weighing 30-35 g were randomly divided into 3 groups (N = 6): untrained, trained eccentric running (16°; TER), and trained running (0°) (TR), and were submitted to an 8-week training program. TER increased muscle oxidative capacity (succinate dehydrogenase and complexes I and II) in a manner similar to TR, and TER did not decrease oxidative damage (xylenol and creatine phosphate) but increased antioxidant enzyme activity (superoxide dismutase and catalase) similar to TR. Muscle damage (creatine kinase) and inflammation (myeloperoxidase) were not reduced by TER. In conclusion, we suggest that TER improves mitochondrial function but does not reduce oxidative stress, muscle damage, or inflammation induced by eccentric contractions.

Evaluación seriada de pacientes asintomáticos con insufciencia aórtica grave y función ventricular normal: estudio basado en el tamaño ventricular y en la lesión valvular / Serial evaluation of asymptomatic patients with severe aortic regurgitation and normal left ventricular systolic function: study based on left ventricular dimensions and valve lesion

Antecedentes: Pacientes asintomáticos con insuficiencia aórtica (IA) grave y función ventricular normal pueden desarrollar síntomas y disfunción ventricular. La lesión valvular en asociación con los índices de tamaño ventricular no fue evaluada hasta ahora, como tampoco la progresión de estos índices en el seguimiento. Objetivo: Identificar en forma seriada las variaciones de los índices de tamaño y de lesión valvular para predecir síntomas, reemplazo valvular, disfunción ventricular y muerte cardíaca. Material y métodos: Se evaluaron 254 pacientes con IA grave aislada (edad media 63 ± 7 años; sexo masculino 74 por ciento; fracción de eyección [FEVI] basal del 64 por ciento ± 5 por ciento), asintomáticos al ingreso. Los puntos finales fueron desarrollo de síntomas, disfunción ventricular (FEVI < 55 por ciento), muerte cardíaca o reemplazo valvular. Resultados: El seguimiento promedio fue de 4,7 ± 2,3 años. Desarrollaron síntomas, disfunción ventricular y reemplazo valvular 72, 97 y 61 pacientes, respectivamente. La mortalidad global fue de 11/254 (4,3 por ciento). En el análisis univariado, la edad, los diámetros de fin de diástole y sístole corregidos por superficie corporal (DFDSC y DFSSC), el área del orificio regurgitante efectivo (AORE), el diámetro de la aurícula izquierda y la FEVI en el ejercicio se asociaron con los puntos finales. Sin embargo, el análisis de Cox identificó las tasas promedio de cambio en el DFSSC y en el AORE y el tamaño ventricular al ingreso (DFDSC y DFSSC) como los predictores independientes. Conclusión: En pacientes asintomáticos con IA grave, las tasas de cambio en el tamaño y en la lesión valvular fueron los predictores independientes relacionados con el desarrollo de síntomas, disfunción ventricular y reemplazo valvular, que favorecieron una mejor estratificación de riesgo.

Indicadores de gestión hospitalaria / Markers of quality in hospital management

Hoy en día la medición es una herramienta que el ser humano ha utilizado para casi cualquier actividad por muy trivial que ésta sea. En el caso de la alta gerencia, todas las teorías administrativas que se puedan o quieran implementar en cualquier empresa, sin importar su giro, terminan con la medición de su estructura, de sus procesos o de sus resultados. En el caso de la vida hospitalaria, estos indicadores de gestión administrativa se han convertido en una herramienta esencial, porque todo lo que no se mide no puede ser mejorado y por tanto, deja de ser útil para una mejor toma de decisiones. Los indicadores de gestión hospitalaria, así son un instrumento de cambio en la estructura de la institución y miden el cumplimiento de los objetivos institucionales.

Measurement is the tool used by humans in all of his daily activities, no matter how simple or complicated. In the case of advanced management, all administrative theories from any business company end up with the measurement of indexes of its processes, structures and results. In the case of everyday hospital life, indexes of administrative management have evolved into an essential tool because things that can not be measured can not be improved; hence, they are worthless for the decision making process. Indexes of administrative management are tools to change the structure of an institution and measure the accomplishment of its objectives.