A Biallelic Truncating Variant in the TPR Domain of GEMIN5 Associated with Intellectual Disability and Cerebral Atrophy.

GEMIN5 is a multifunctional RNA-binding protein required for the assembly of survival motor neurons. Several bi-allelic truncating and missense variants in this gene are reported to cause a neurodevelopmental disorder characterized by cerebellar atrophy, intellectual disability (ID), and motor dysfunction. Whole exome sequencing of a Pakistani consanguineous family with three brothers affected by ID, cerebral atrophy, mobility, and speech impairment revealed a novel homozygous 3bp-deletion NM_015465.5:c.3162_3164del that leads to the loss of NM_015465.5 (NP_056280.2):p. (Asp1054_Ala1055delinsGlu) amino acid in one of the α-helixes of the tetratricopeptide repeats of GEMIN5. In silico 3D representations of the GEMIN5 dimerization domain show that this variant likely affects the orientation of the downstream sidechains out of the helix axis, which would affect the packing with neighboring helices. The phenotype of all affected siblings overlaps well with previously reported patients, suggesting that NM_015465.5: c.3162_3164del (NP_056280.2):p. (Asp1054_Ala1055delinsGlu) is a novel GEMIN5 pathogenic variant. Overall, our data expands the molecular and clinical phenotype of the recently described neurodevelopmental disorder with cerebellar atrophy and motor dysfunction (NEDCAM) syndrome

Multiple imputations applied to the DREAM3 phosphoproteomics challenge: a winning strategy.

DREAM is an initiative that allows researchers to assess how well their methods or approaches can describe and predict networks of interacting molecules [1]. Each year, recently acquired datasets are released to predictors ahead of publication. Researchers typically have about three months to predict the masked data or network of interactions, using any predictive method. Predictions are assessed prior to an annual conference where the best predictions are unveiled and discussed. Here we present the strategy we used to make a winning prediction for the DREAM3 phosphoproteomics challenge. We used Amelia II, a multiple imputation software method developed by Gary King, James Honaker and Matthew Blackwell[2] in the context of social sciences to predict the 476 out of 4624 measurements that had been masked for the challenge. To chose the best possible multiple imputation parameters to apply for the challenge, we evaluated how transforming the data and varying the imputation parameters affected the ability to predict additionally masked data. We discuss the accuracy of our findings and show that multiple imputations applied to this dataset is a powerful method to accurately estimate the missing data. We postulate that multiple imputations methods might become an integral part of experimental design as a mean to achieve cost savings in experimental design or to increase the quantity of samples that could be handled for a given cost

DBnorm as an R package for the comparison and selection of appropriate statistical methods for batch effect correction in metabolomic studies.

As a powerful phenotyping technology, metabolomics provides new opportunities in biomarker discovery through metabolome-wide association studies (MWAS) and the identification of metabolites having a regulatory effect in various biological processes. While mass spectrometry-based (MS) metabolomics assays are endowed with high throughput and sensitivity, MWAS are doomed to long-term data acquisition generating an overtime-analytical signal drift that can hinder the uncovering of real biologically relevant changes. We developed "dbnorm", a package in the R environment, which allows for an easy comparison of the model performance of advanced statistical tools commonly used in metabolomics to remove batch effects from large metabolomics datasets. "dbnorm" integrates advanced statistical tools to inspect the dataset structure not only at the macroscopic (sample batches) scale, but also at the microscopic (metabolic features) level. To compare the model performance on data correction, "dbnorm" assigns a score that help users identify the best fitting model for each dataset. In this study, we applied "dbnorm" to two large-scale metabolomics datasets as a proof of concept. We demonstrate that "dbnorm" allows for the accurate selection of the most appropriate statistical tool to efficiently remove the overtime signal drift and to focus on the relevant biological components of complex datasets

Virosaurus A Reference to Explore and Capture Virus Genetic Diversity.

The huge genetic diversity of circulating viruses is a challenge for diagnostic assays for emerging or rare viral diseases. High-throughput technology offers a new opportunity to explore the global virome of patients without preconception about the culpable pathogens. It requires a solid reference dataset to be accurate. Virosaurus has been designed to offer a non-biased, automatized and annotated database for clinical metagenomics studies and diagnosis. Raw viral sequences have been extracted from GenBank, and cleaned up to remove potentially erroneous sequences. Complete sequences have been identified for all genera infecting vertebrates, plants and other eukaryotes (insect, fungus, etc.). To facilitate the analysis of clinically relevant viruses, we have annotated all sequences with official and common virus names, acronym, genotypes, and genomic features (linear, circular, DNA, RNA, etc.). Sequences have been clustered to remove redundancy at 90% or 98% identity. The analysis of clustering results reveals the state of the virus genetic landscape knowledge. Because herpes and poxviruses were under-represented in complete genomes considering their potential diversity in nature, we used genes instead of complete genomes for those in Virosaurus

Nuevas ruralidades: Prácticas de Formación y Extensión Universitaria, un diálogo posible

Desde la Facultad de Trabajo Social de La Plata y la Extensión Universitaria se interviene en el territorio Isla Paulino, ubicado en Berisso, provincia de Buenos aires. Su importancia radica en las características del lugar, siendo considerado entre los espacios llamados ruralidades, donde la dinámica de las diferentes carreras, deben abordar los temas que competen al territorio de una manera muy particular. Daremos cuenta de lo trabajado durante nuestras prácticas de formación profesional durante el año 2016 en el marco de la cátedra Trabajo Social III, dependiente de la UNLP. Trabajo que fue generador del actual proyecto de extensión universitaria “Estrategias colectivas para la articulación y cogestión multiactoral”. En Isla Paulino los tiempos que se manejan son propios del lugar; las relaciones dinámicas y complejas entre los factores económicos, sociales, culturales, ambientales y político-institucionales caracterizan al territorio. El principal motivo que lleva a abordar este territorio es la importancia de visibilizar las problemáticas que presentan en él, es decir, las expresiones de la cuestión social que se manifiestan en él.Facultad de Trabajo Socia

Capture and return of sexual genomes by hybridogenetic frogs provide clonal genome enrichment in a sexual species.

Hybridogenesis is a reproductive tool for sexual parasitism. Hybridogenetic hybrids use gametes from their sexual host for their own reproduction, but sexual species gain no benefit from such matings as their genome is later eliminated. Here, we examine the presence of sexual parasitism in water frogs through crossing experiments and genome-wide data. We specifically focus on the famous Central-European populations where Pelophylax esculentus males (hybrids of P. ridibundus and P. lessonae) live with P. ridibundus. We identified a system where the hybrids commonly produce two types of clonal gametes (hybrid amphispermy). The haploid lessonae genome is clonally inherited from generation to generation and assures the maintenance of hybrids through a process, in which lessonae sperm fertilize P. ridibundus eggs. The haploid ridibundus genome in hybrids received from P. ridibundus a generation ago, is perpetuated as clonal ridibundus sperm and used to fertilize P. ridibundus eggs, yielding female P. ridibundus progeny. These results imply animal reproduction in which hybridogenetic taxa are not only sexual parasites, but also participate in the formation of a sexual taxon in a remarkable way. This occurs through a process by which sexual gametes are being captured, converted to clones, and returned to sexual populations in one generation

Soil protist function varies with elevation in the Swiss Alps

Protists are abundant and play key trophic functions in soil. Documenting how their trophic contributions vary across large environmental gradients is essential to understand and predict how biogeochemical cycles will be impacted by global changes. Here, using amplicon sequencing of environmental DNA in open habitat soil from 161 locations spanning 2600 m of elevation in the Swiss Alps (from 400 to 3000 m), we found that, over the whole study area, soils are dominated by consumers, followed by parasites and phototrophs. In contrast, the proportion of these groups in local communities shows large variations in relation to elevation. While there is, on average, three times more consumers than parasites at low elevation (400–1000 m), this ratio increases to 12 at high elevation (2000–3000 m). This suggests that the decrease in protist host biomass and diversity toward mountains tops impact protist functional composition. Furthermore, the taxonomic composition of protists that infect animals was related to elevation while that of protists that infect plants or of protist consumers was related to soil pH. This study provides a first step to document and understand how soil protist functions vary along the elevational gradient

Introduction of a urodynamic score to detect pre- and postoperative neurological deficits in children with a primary tethered cord.

OBJECT: An increasing number of asymptomatic children are diagnosed with occult spinal dysraphism, raising the question of their optimal management. Urodynamic study (UDS) is the most reliable method of detecting neuro-urological abnormalities in these children. The rate of postoperative retethering ranges from 10 to 20% and is not always immediately clinically significant. The aim of this prospective study was to develop a reliable method that could be used in the preoperative assessment and postoperative follow-up of children with a tethered cord syndrome (TCS). METHODS: From 1989 to 1997, 15 children underwent spinal cord untethering for TCS. Preoperatively, patients were assessed with MRI and UDS. Postoperative UDS were repeated at 6- to 12-month intervals. Four UDS parameters were identified, graded, and added to obtain a UDS score. A group of 38 children without dysraphic condition was used as control and allowed the calculation of a normal score. CONCLUSIONS: There was a statistically significant difference in the preoperative UDS scores between the control group and the study group ( p<0.001). Postoperatively, there was a statistically significant improvement ( p<0.001) in UDS scores. UDS score is a reliable tool for identifying and quantifying neuro-urological disorders in patients with TCS. Postoperatively, this score was useful in the early diagnosis of spinal cord retethering