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The developing limb is one of the main model systems to study biological pattern formation and evolutionary adaptation. Of particular importance is the establishment of dorso-ventral patterning (DV) as it gives rise to crucial DV asymmetries in the skeletal elements, nerves and vessels that enable the appendages to serve crucial functions such as stable locomotion on land and detailed manipulation.

The dorso-ventral (DV) limb asymmetry is crucial for its function; however, little is known about how it is accomplished during morphogenesis. Lmx1b is the key regulator of DV patterning during limb development as it is both necessary and sufficient to specify dorsal fates, but its regulation remains poorly known. We recently demonstrated a complex autoregulatory mode of transcriptional Lmx1b regulation mediated by two limb-specific enhancers, LARM1 and LARM2. The deletion of both enhancers (dLARM1/2) reproduces the Lmx1b-null phenotype in the limb, while the removal of each enhancer produced a double ventral phenotype restricted to the posterior (dLARM1) or anterior (dLARM2) half of the limb. To investigate the regulatory logic of the Lmx1b locus in detail, we dissected the LARM1 element into its enhancer and silencer sequences and explored the functional contribution of the two Lmx1b-associated lncRNAs. The results confirm the presence of a functional repressor contained in LARM1 and underscore the positional specificity of the LARM sequences. The data suggests that Lmx1b transcription uses different regulatory elements in different positions probably reflecting the integration of the local transcriptional environment. Indeed, published ChIP-seq data showed the Gli3 and Hox13 are significantly enriched in the LARM sequences exposing their interaction with major limb regulators. Finally, considering that the double-ventral limbs of dLARM1/2 mutants fail to support locomotion, even to lift the body weight, we hypothesized that the elaboration of the DV asymmetry by modification of Lmx1b regulation, or its functional targets, had to accompany the fin to limb transition. We have identified orthologs of the LARMs in fishes and all of them show activity in the pectoral fin in zebrafish reporter essays, revealing the deep roots of Lmx1b regulation.

Metagenomics-based high-throughput sequencing (HTS) enables comprehensive detection of all species comprised in a sample with a single assay and is becoming a standard method for outbreak investigation. However, unlike real-time PCR or serological assays, HTS datasets generated for pathogen detection do not easily provide yes/no answers. Rather, results of the taxonomic read assignment need to be assessed by trained personnel to gain information thereof. Proficiency tests are important instruments of validation, harmonization, and standardization. Within the European Union funded project COMPARE [COllaborative Management Platform for detection and Analyses of (Re-) emerging and foodborne outbreaks in Europe], we conducted a proficiency test to scrutinize the ability to assess diagnostic metagenomics data. An artificial dataset resembling shotgun sequencing of RNA from a sample of contaminated trout was provided to 12 participants with the request to provide a table with per-read taxonomic assignments at species level and a report with a summary and assessment of their findings, considering different categories like pathogen, background, or contaminations. Analysis of the read assignment tables showed that the software used reliably classified the reads taxonomically overall. However, usage of incomplete reference databases or inappropriate data pre-processing caused difficulties. From the combination of the participants’ reports with their read assignments, we conclude that, although most species were detected, a number of important taxa were not or not correctly categorized. This implies that knowledge of and awareness for potentially dangerous species and contaminations need to be improved, hence, capacity building for the interpretation of diagnostic metagenomics datasets is necessary.

Summary: Cell differentiation processes are achieved through a continuum of hierarchical intermediate cell states that might be captured by single-cell RNA seq. Existing computational approaches for the assessment of cell-state hierarchies from single-cell data can be formalized under a general framework composed of (i) a metric to assess cell-to-cell similarities (with or without a dimensionality reduction step) and (ii) a graph-building algorithm (optionally making use of a cell clustering step). The Sincell R package implements a methodological toolbox allowing flexible workflows under such a framework. Furthermore, Sincell contributes new algorithms to provide cell-state hierarchies with statistical support while accounting for stochastic factors in single-cell RNA seq. Graphical representations and functional association tests are provided to interpret hierarchies. The functionalities of Sincell are illustrated in a real case study, which demonstrates its ability to discriminate noisy from stable cell-state hierarchies. Availability and implementation: Sincell is an open-source R/Bioconductor package available at http://bioconductor.org/packages/sincell. A detailed manual and a vignette are provided with the package. Contact: antonio.rausell@isb-sib.ch Supplementary information: Supplementary data are available at Bioinformatics online

[Resumen] En este artículo se presenta un estudio de alineamiento 3D de diferentes posiciones de un robot en entornos de interior. El alineamiento que se desea resolver se desenvuelve en escenarios de difícil caracterización. Para resolver este problema se plantea utilizar información RGB-D, esto es, información visual y de profundidad obtenida del entorno a través de cámaras y sensores láseres respectivamente. En primer lugar se expone el algoritmo desarrollado a través de información visual. Después se expone el algoritmo desarrollado para información de profundidad. Finalmente, se presenta un algoritmo que resuelve las situaciones en las cuales el alineamiento entre dos poses no es correcto.

This work describes the analysis of 196 Ebolavirus genomes and the identification of specificity determining positions (SDPs) in all nine Ebolavirus proteins that distinguish the non human pathogenic Reston viruses from the four human pathogenic Ebolaviruses. Structural analysis was performed to identify those SDPs that are likely to have a functional effect. This analysis revealed novel functional insights, in particular for Ebolavirus proteins VP40 and VP24. The VP40 SDP P85T interferes with VP40 function by altering octamer formation. The VP40 SDP Q245P affects the structure and hydrophobic core of the protein and consequently protein function. Three VP24 SDPs (T131S, M136L, Q139R) are likely to impair VP24 binding to human karyopherin alpha5 (KPNA5) and therefore inhibition of interferon signaling. Since VP24 is critical for Ebolavirus adaptation to novel hosts, and only a few SDPs distinguish Reston virus VP24 from VP24 of other Ebolaviruses, human pathogenic Reston viruses may emerge