PICMI: mapping point mutations on genomes

Motivation: Several international collaborations and local projects are producing extensive catalogues of genomic variations that are supplementing existing collections such as the OMIM catalogue. The flood of this type of data will keep increasing and, especially, it will be relevant to a wider user base, including not only molecular biologists, geneticists and bioinformaticians, but also clinical researchers. Mapping the observed variations, sometimes only described at the amino acid level, on a genome, identifying whether they affect a gene and—if so—whether they also affect different isoforms of the same gene, is a time consuming and often frustrating task

Fiber transport of spatially entangled photons

Entanglement in the spatial degrees of freedom of photons is an interesting resource for quantum information. For practical distribution of such entangled photons it is desireable to use an optical fiber, which in this case has to support multiple transverse modes. Here we report the use of a hollow-core photonic crystal fiber to transport spatially entangled qubits.Comment: 4 pages, 4 figure

Selection and Modelling of a New Single-Domain Intrabody Against TDP-43

Amyotrophic lateral sclerosis (ALS) is a neurodegenerative disorder associated to deteriorating motor and cognitive functions, and short survival. The disease is caused by neuronal death which results in progressive muscle wasting and weakness, ultimately leading to lethal respiratory failure. The misbehaviour of a specific protein, TDP-43, which aggregates and becomes toxic in ALS patient’s neurons, is supposed to be one of the causes. TDP-43 is a DNA/RNA-binding protein involved in several functions related to nucleic acid metabolism. Sequestration of TDP-43 aggregates is a possible therapeutic strategy that could alleviate or block pathology. Here, we describe the selection and characterization of a new intracellular antibody (intrabody) against TDP-43 from a llama nanobody library. The structure of the selected intrabody was predicted in silico and the model was used to suggest mutations that enabled to improve its expression yield, facilitating its experimental validation. We showed how coupling experimental methodologies with in silico design may allow us to obtain an antibody able to recognize the RNA binding regions of TDP-43. Our findings illustrate a strategy for the mitigation of TDP-43 proteinopathy in ALS and provide a potential new tool for diagnostics

T cell receptor sequence clustering and antigen specificity

There has been increasing interest in the role of T cells and their involvement in cancer, autoimmune and infectious diseases. However, the nature of T cell receptor (TCR) epitope recognition at a repertoire level is not yet fully understood. Due to technological advances a plethora of TCR sequences from a variety of disease and treatment settings has become readily available. Current efforts in TCR specificity analysis focus on identifying characteristics in immune repertoires which can explain or predict disease outcome or progression, or can be used to monitor the efficacy of disease therapy. In this context, clustering of TCRs by sequence to reflect biological similarity, and especially to reflect antigen specificity have become of paramount importance. We review the main TCR sequence clustering methods and the different similarity measures they use, and discuss their performance and possible improvement. We aim to provide guidance for non-specialists who wish to use TCR repertoire sequencing for disease tracking, patient stratification or therapy prediction, and to provide a starting point for those aiming to develop novel techniques for TCR annotation through clustering

A database of immunoglobulins with integrated tools: DIGIT

The DIGIT (Database of ImmunoGlobulins with Integrated Tools) database (http://biocomputing.it/digit) is an integrated resource storing sequences of annotated immunoglobulin variable domains and enriched with tools for searching and analyzing them. The annotations in the database include information on the type of antigen, the respective germline sequences and on pairing information between light and heavy chains. Other annotations, such as the identification of the complementarity determining regions, assignment of their structural class and identification of mutations with respect to the germline, are computed on the fly and can also be obtained for user-submitted sequences. The system allows customized BLAST searches and automatic building of 3D models of the domains to be performed

Socio-demographic and clinical characterization of patients with obsessive-compulsive tic-related disorder (OCTD) : An Italian multicenter study

© Copyright by Pacini Editore SrlIn the DSM-5 a new "tic-related" specifier for obsessive compulsive disorder (OCD) has been introduced, highlighting the importance of an accurate characterization of patients suffering from obsessive-compulsive tic-related disorder ("OCTD"). In order to characterize OCTD from a socio-demographic and clinical perspective, the present multicenter study was carried out. The sample consists of 266 patients, divided in two groups with lifetime diagnoses of OCD and OCTD, respectively. OCTD vs OCD patients showed a significant male prevalence (68.5% vs 48.5%; p < .001), a higher rate of psychiatric comorbidities (69.4 vs 50%; p < .001) - mainly with neurodevelopmental disorders (24 vs 0%; p < .001), a lower education level and professional status (middle school diploma: 25 vs 7.6%; full-Time job 44.4 vs 58%; p < .001). Moreover, OCTD vs OCD patients showed significantly earlier age of OCD and psychiatric comorbidity onsets (16.1 ± 10.8 vs 22.1 ± 9.5 years; p < .001, and 18.3 ± 12.8 vs 25.6 ± 9.4: p < .001, respectively). Patients with OCTD patients were treated mainly with antipsychotic and with a low rate of benzodiazepine (74.2 vs 38.2% and 20.2 vs 31.3%, respectively; p < .001). Finally, OCTD vs OCD patients showed higher rates of partial treatment response (58.1 vs 38%; p < .001), lower rates of current remission (35.5 vs 54.8%; p < .001) and higher rates of suicidal ideation (63.2 vs 41.7%; p < .001) and attempts (28.9 vs 8.3%; p < .001). Patients with OCTD report several unfavorable socio-demographic and clinical characteristics compared to OCD patients without a history of tic. Additional studies on larger sample are needed to further characterize OCTD patients from clinical and therapeutic perspectives.Peer reviewedFinal Published versio

Detectors for the next-generation PET scanners

Next-generation PET scanners are expected to fulfill very high requirements in terms of spatial, energy and timing resolution. Modern scanner performances are inherently limited by the use of standard photomultiplier tubes. The use of Silicon Photomultiplier (SiPM) matrices is proposed for the construction of a small animal PET system with depth of interaction capabilities. Measurements showing that SiPM matrices are highly ideal for PET applications, have been reported

Effects of natural selection and gene conversion on the evolution of human glycophorins coding for MNS blood polymorphisms in malaria-endemic African populations

Malaria has been a very strong selection pressure in recent human evolution, particularly in Africa. Of the one million deaths per year due to malaria, more than 90% are in sub-Saharan Africa, a region with high levels of genetic variation and population substructure. However, there have been few studies of nucleotide variation at genetic loci that are relevant to malaria susceptibility across geographically and genetically diverse ethnic groups in Africa. Invasion of erythrocytes by Plasmodium falciparum parasites is central to the pathology of malaria. Glycophorin A (GYPA) and B (GYPB), which determine MN and Ss blood types, are two major receptors that are expressed on erythrocyte surfaces and interact with parasite ligands. We analyzed nucleotide diversity of the glycophorin gene family in 15 African populations with different levels of malaria exposure. High levels of nucleotide diversity and gene conversion were found at these genes. We observed divergent patterns of genetic variation between these duplicated genes and between different extracellular domains of GYPA. Specifically, we identified fixed adaptive changes at exons 3-4 of GYPA. By contrast, we observed an allele frequency spectrum skewed toward a significant excess of intermediate-frequency alleles at GYPA exon 2 in many populations; the degree of spectrum distortion is correlated with malaria exposure, possibly because of the joint effects of gene conversion and balancing selection. We also identified a haplotype causing three amino acid changes in the extracellular domain of glycophorin B. This haplotype might have evolved adaptively in five populations with high exposure to malaria

FunClust: a web server for the identification of structural motifs in a set of non-homologous protein structures

The occurrence of very similar structural motifs brought about by different parts of non homologous proteins is often indicative of a common function. Indeed, relatively small local structures can mediate binding to a common partner, be it a protein, a nucleic acid, a cofactor or a substrate. While it is relatively easy to identify short amino acid or nucleotide sequence motifs in a given set of proteins or genes, and many methods do exist for this purpose, much more challenging is the identification of common local substructures, especially if they are formed by non consecutive residues in the sequence

IEDB-AR: immune epitope database - analysis resource in 2019

The Immune Epitope Database Analysis Resource (IEDB-AR, http://tools.iedb.org/) is a companion website to the IEDB that provides computational tools focused on the prediction and analysis of B and T cell epitopes. All of the tools are freely available through the public website and many are also available through a REST API and/or a downloadable command-line tool. A virtual machine image of the entire site is also freely available for non-commercial use and contains most of the tools on the public site. Here, we describe the tools and functionalities that are available in the IEDB-AR, focusing on the 10 new tools that have been added since the last report in the 2012 NAR webserver edition. In addition, many of the tools that were already hosted on the site in 2012 have received updates to newest versions, including NetMHC, NetMHCpan, BepiPred and DiscoTope. Overall, this IEDB-AR update provides a substantial set of updated and novel features for epitope prediction and analysis.Fil: Dhanda, Sandeep Kumar. La Jolla Institute for Allergy and Immunology; Estados UnidosFil: Mahajan, Swapnil. La Jolla Institute for Allergy and Immunology; Estados UnidosFil: Paul, Sinu. La Jolla Institute for Allergy and Immunology; Estados UnidosFil: Yan, Zhen. La Jolla Institute for Allergy and Immunology; Estados UnidosFil: Kim, Haeuk. La Jolla Institute for Allergy and Immunology; Estados UnidosFil: Jespersen, Martin Closter. Technical University of Denmark; DinamarcaFil: Jurtz, Vanessa. Technical University of Denmark; DinamarcaFil: Andreatta, Massimo. Consejo Nacional de Investigaciones Científicas y Técnicas. Centro Científico Tecnológico Conicet - La Plata. Instituto de Investigaciones Biotecnológicas. Universidad Nacional de San Martín. Instituto de Investigaciones Biotecnológicas; Argentina. Technical University of Denmark; DinamarcaFil: Greenbaum, Jason A. La Jolla Institute for Allergy and Immunology; Estados UnidosFil: Marcatili, Paolo. Technical University of Denmark; DinamarcaFil: Sette, Alessandro. La Jolla Institute for Allergy and Immunology; Estados Unidos. University of California; Estados UnidosFil: Nielsen, Morten. Technical University of Denmark; Dinamarca. Consejo Nacional de Investigaciones Científicas y Técnicas. Centro Científico Tecnológico Conicet - La Plata. Instituto de Investigaciones Biotecnológicas. Universidad Nacional de San Martín. Instituto de Investigaciones Biotecnológicas; ArgentinaFil: Peters, Bjoern. University of California; Estados Unidos. La Jolla Institute for Allergy and Immunology; Estados Unido