The conserved core of the nereid brain: Circular CNS, apical nervous system and lhx6-arx-dlx neurons.

When bilaterian animals first emerged, an enhanced perception of the Precambrian environment was key to their stunning success. This occurred through the acquisition of an anterior brain, as found in most extant bilaterians. What were the core circuits of the first brain, and how do they relate to today's diversity? With two landmark resources - the full connectome and a multimodal cellular atlas combining gene expression and ultrastructure - the young worm of the marine annelid Platynereis dumerilii takes center stage in comparative bilaterian neuroanatomy. The new data suggest a composite structure of the ancestral bilaterian brain, with the anterior end of a circular CNS fused to a sensory-neurosecretory apical system, and with lhx6-arx-dlx chemosensory circuits giving rise to associative centers in the descending bilaterian lineages.

The Nereid on the rise: Platynereis as a model system.

The Nereid Platynereis dumerilii (Audouin and Milne Edwards (Annales des Sciences Naturelles 1:195-269, 1833) is a marine annelid that belongs to the Nereididae, a family of errant polychaete worms. The Nereid shows a pelago-benthic life cycle: as a general characteristic for the superphylum of Lophotrochozoa/Spiralia, it has spirally cleaving embryos developing into swimming trochophore larvae. The larvae then metamorphose into benthic worms living in self-spun tubes on macroalgae. Platynereis is used as a model for genetics, regeneration, reproduction biology, development, evolution, chronobiology, neurobiology, ecology, ecotoxicology, and most recently also for connectomics and single-cell genomics. Research on the Nereid started with studies on eye development and spiralian embryogenesis in the nineteenth and early twentieth centuries. Transitioning into the molecular era, Platynereis research focused on posterior growth and regeneration, neuroendocrinology, circadian and lunar cycles, fertilization, and oocyte maturation. Other work covered segmentation, photoreceptors and other sensory cells, nephridia, and population dynamics. Most recently, the unique advantages of the Nereid young worm for whole-body volume electron microscopy and single-cell sequencing became apparent, enabling the tracing of all neurons in its rope-ladder-like central nervous system, and the construction of multimodal cellular atlases. Here, we provide an overview of current topics and methodologies for P. dumerilii, with the aim of stimulating further interest into our unique model and expanding the active and vibrant Platynereis community.

Whole-body integration of gene expression and single-cell morphology.

Animal bodies are composed of cell types with unique expression programs that implement their distinct locations, shapes, structures, and functions. Based on these properties, cell types assemble into specific tissues and organs. To systematically explore the link between cell-type-specific gene expression and morphology, we registered an expression atlas to a whole-body electron microscopy volume of the nereid Platynereis dumerilii. Automated segmentation of cells and nuclei identifies major cell classes and establishes a link between gene activation, chromatin topography, and nuclear size. Clustering of segmented cells according to gene expression reveals spatially coherent tissues. In the brain, genetically defined groups of neurons match ganglionic nuclei with coherent projections. Besides interneurons, we uncover sensory-neurosecretory cells in the nereid mushroom bodies, which thus qualify as sensory organs. They furthermore resemble the vertebrate telencephalon by molecular anatomy. We provide an integrated browser as a Fiji plugin for remote exploration of all available multimodal datasets.

Standardized and reproducible measurement of decision-making in mice.

Progress in science requires standardized assays whose results can be readily shared, compared, and reproduced across laboratories. Reproducibility, however, has been a concern in neuroscience, particularly for measurements of mouse behavior. Here, we show that a standardized task to probe decision-making in mice produces reproducible results across multiple laboratories. We adopted a task for head-fixed mice that assays perceptual and value-based decision making, and we standardized training protocol and experimental hardware, software, and procedures. We trained 140 mice across seven laboratories in three countries, and we collected 5 million mouse choices into a publicly available database. Learning speed was variable across mice and laboratories, but once training was complete there were no significant differences in behavior across laboratories. Mice in different laboratories adopted similar reliance on visual stimuli, on past successes and failures, and on estimates of stimulus prior probability to guide their choices. These results reveal that a complex mouse behavior can be reproduced across multiple laboratories. They establish a standard for reproducible rodent behavior, and provide an unprecedented dataset and open-access tools to study decision-making in mice. More generally, they indicate a path toward achieving reproducibility in neuroscience through collaborative open-science approaches.

In science, it is of vital importance that multiple studies corroborate the same result. Researchers therefore need to know all the details of previous experiments in order to implement the procedures as exactly as possible. However, this is becoming a major problem in neuroscience, as animal studies of behavior have proven to be hard to reproduce, and most experiments are never replicated by other laboratories. Mice are increasingly being used to study the neural mechanisms of decision making, taking advantage of the genetic, imaging and physiological tools that are available for mouse brains. Yet, the lack of standardized behavioral assays is leading to inconsistent results between laboratories. This makes it challenging to carry out large-scale collaborations which have led to massive breakthroughs in other fields such as physics and genetics. To help make these studies more reproducible, the International Brain Laboratory (a collaborative research group) et al. developed a standardized approach for investigating decision making in mice that incorporates every step of the process; from the training protocol to the software used to analyze the data. In the experiment, mice were shown images with different contrast and had to indicate, using a steering wheel, whether it appeared on their right or left. The mice then received a drop of sugar water for every correction decision. When the image contrast was high, mice could rely on their vision. However, when the image contrast was very low or zero, they needed to consider the information of previous trials and choose the side that had recently appeared more frequently. This method was used to train 140 mice in seven laboratories from three different countries. The results showed that learning speed was different across mice and laboratories, but once training was complete the mice behaved consistently, relying on visual stimuli or experiences to guide their choices in a similar way. These results show that complex behaviors in mice can be reproduced across multiple laboratories, providing an unprecedented dataset and open-access tools for studying decision making. This work could serve as a foundation for other groups, paving the way to a more collaborative approach in the field of neuroscience that could help to tackle complex research challenges.

miR-206 is required for changes in cell adhesion that drive muscle cell morphogenesis in Xenopus laevis.

MicroRNAs (miRNAs) are highly conserved small non-coding RNA molecules that post-transcriptionally regulate gene expression in multicellular organisms. Within the set of muscle-specific miRNAs, miR-206 expression is largely restricted to skeletal muscle and is found exclusively within the bony fish lineage. Although many studies have implicated miR-206 in muscle maintenance and disease, its role in skeletal muscle development remains largely unknown. Here, we examine the role of miR-206 during Xenopus laevis somitogenesis. In Xenopus laevis, miR-206 expression coincides with the onset of somitogenesis. We show that both knockdown and over-expression of miR-206 result in abnormal somite formation affecting muscle cell rotation, attachment, and elongation. In particular, our data suggests that miR-206 regulates changes in cell adhesion that affect the ability of newly formed somites to adhere to the notochord as well as to the intersomitic boundaries. Additionally, we show that ß-dystroglycan and F-actin expression levels are significantly reduced, suggesting that knockdown of miR-206 levels affects cellular mechanics necessary for cell shape changes and attachments that are required for proper muscle formation.

Whole-Body Single-Cell Sequencing Reveals Transcriptional Domains in the Annelid Larval Body.

Animal bodies comprise diverse arrays of cells. To characterize cellular identities across an entire body, we have compared the transcriptomes of single cells randomly picked from dissociated whole larvae of the marine annelid Platynereis dumerilii. We identify five transcriptionally distinct groups of differentiated cells, each expressing a unique set of transcription factors and effector genes that implement cellular phenotypes. Spatial mapping of cells into a cellular expression atlas, and wholemount in situ hybridization of group-specific genes reveals spatially coherent transcriptional domains in the larval body, comprising, for example, apical sensory-neurosecretory cells versus neural/epidermal surface cells. These domains represent new, basic subdivisions of the annelid body based entirely on differential gene expression, and are composed of multiple, transcriptionally similar cell types. They do not represent clonal domains, as revealed by developmental lineage analysis. We propose that the transcriptional domains that subdivide the annelid larval body represent families of related cell types that have arisen by evolutionary diversification. Their possible evolutionary conservation makes them a promising tool for evo-devo research.

Spatial Transcriptomics: Constructing a Single-Cell Resolution Transcriptome-Wide Expression Atlas.

The method described here aims at the construction of a single-cell resolution gene expression atlas for an animal or tissue, combining in situ hybridization (ISH) and single-cell mRNA-sequencing (scRNAseq).A high resolution and medium-coverage gene expression atlas of an animal or tissue of interest can be obtained by performing a series of ISH experiments, followed by a process of image registration and gene expression averaging. Using the overlapping fraction of the genes, concomitantly obtained scRNAseq data can be fitted into the spatial context of the gene expression atlas, complementing the coverage by genes.

Whole-organism cellular gene-expression atlas reveals conserved cell types in the ventral nerve cord of Platynereis dumerilii.

The comparative study of cell types is a powerful approach toward deciphering animal evolution. To avoid selection biases, however, comparisons ideally involve all cell types present in a multicellular organism. Here, we use image registration and a newly developed "Profiling by Signal Probability Mapping" algorithm to generate a cellular resolution 3D expression atlas for an entire animal. We investigate three-segmented young worms of the marine annelid Platynereis dumerilii, with a rich diversity of differentiated cells present in relatively low number. Starting from whole-mount expression images for close to 100 neural specification and differentiation genes, our atlas identifies and molecularly characterizes 605 bilateral pairs of neurons at specific locations in the ventral nerve cord. Among these pairs, we identify sets of neurons expressing similar combinations of transcription factors, located at spatially coherent anterior-posterior, dorsal-ventral, and medial-lateral coordinates that we interpret as cell types. Comparison with motor and interneuron types in the vertebrate neural tube indicates conserved combinations, for example, of cell types cospecified by Gata1/2/3 and Tal transcription factors. These include V2b interneurons and the central spinal fluid-contacting Kolmer-Agduhr cells in the vertebrates, and several neuron types in the intermediate ventral ganglionic mass in the annelid. We propose that Kolmer-Agduhr cell-like mechanosensory neurons formed part of the mucociliary sole in protostome-deuterostome ancestors and diversified independently into several neuron types in annelid and vertebrate descendants.

Cómo realizar e interpretar una manometría esofágica de alta resolución usando la clasificación de Chicago 3. 0 / How to perform and interpret a high resolution esophageal manometry using the Chicago 3.0 classification

Resumen Con la introducción de la manometría esofágica de alta resolución se revelaron patrones no identificados previamente de la función esofágica. De igual forma, este método diagnóstico adiciona patrones de presión topográfica de la presión esofágica, lo que lleva al desarrollo de nuevas herramientas para el análisis y clasificación de desórdenes motores esofágicos. En la actualidad, la clasificación de Chicago 3.0 es la herramienta de análisis de los diferentes trastornos motores esofágicos. En Colombia, cada día se ve el crecimiento en la realización de este estudio. El artículo propone hacer una revisión de cómo realizar e interpretar una manometría esofágica de alta resolución y clasificar los diferentes trastornos de la motilidad esofágica según la última actualización de la clasificación de Chicago 3.0.

Abstract The introduction of high resolution esophageal manometry has led to the revelation of previously unidentified patterns of esophageal function. Similarly, this diagnostic method has revealed topographic patterns of esophageal pressure which has led to the development of new tools for analysis and classification of esophageal motility disorders. Currently, the Chicago 3.0 classification has become a tool for analysis of the various esophageal motility disorders. In Colombia, the use of this study is spreading and growing. This article reviews of how to perform and interpret high resolution esophageal manometry and shows how to classify esophageal motility disorders according to the latest update of Chicago 3.0.

The Role of Sdf-1α signaling in Xenopus laevis somite morphogenesis.

BACKGROUND: Stromal derived factor-1α (sdf-1α), a chemoattractant chemokine, plays a major role in tumor growth, angiogenesis, metastasis, and in embryogenesis. The sdf-1α signaling pathway has also been shown to be important for somite rotation in zebrafish (Hollway et al., 2007). Given the known similarities and differences between zebrafish and Xenopus laevis somitogenesis, we sought to determine whether the role of sdf-1α is conserved in Xenopus laevis. RESULTS: Using a morpholino approach, we demonstrate that knockdown of sdf-1α or its receptor, cxcr4, leads to a significant disruption in somite rotation and myotome alignment. We further show that depletion of sdf-1α or cxcr4 leads to the near absence of ß-dystroglycan and laminin expression at the intersomitic boundaries. Finally, knockdown of sdf-1α decreases the level of activated RhoA, a small GTPase known to regulate cell shape and movement. CONCLUSION: Our results show that sdf-1α signaling regulates somite cell migration, rotation, and myotome alignment by directly or indirectly regulating dystroglycan expression and RhoA activation. These findings support the conservation of sdf-1α signaling in vertebrate somite morphogenesis; however, the precise mechanism by which this signaling pathway influences somite morphogenesis is different between the fish and the frog.

Causas y maneras de muerte según el Instituto de Medicina Legal en Bogotá: 1986 / Causes and ways if death according to the Institute de Medicina Legal in Bogota: 1986

Nuestro trabajo se basó en los datos obtenidos de las historias de necropsias realizadas en el Instituto de Medicina Legal de Bogotá durante el año de 1986.Las historias se clasificaron de acuerdo a la manera de muerte correspondiente (homicidio, suicidio, accidental, indeterminada y natural). Encontramos como primera manera de muerte el homicidio, con un 41.66 por ciento, seguido de muerte accidental, con un 29.11 por ciento, luego muerte natural con un 18.78 por ciento, luego indeterminada con un 5.42 por ciento y finalmente suicidio con el 5.03 por ciento. Hemos tratado de dar una explicación de los datos encontrados a través de una sustentación teórica. Con este trabajo queremos mostrar, como la violencia en Colombia ha aumentado notoriamente en comparación con años anteriores, y de manera especial, el homicidio, el cual ha pasado a ser la segunda causa de muerte dentro de la mortalidad general