Image processing tools for the validation of CryoEM maps.

The number of maps deposited in public databases (Electron Microscopy Data Bank, EMDB) determined by cryo-electron microscopy has quickly grown in recent years. With this rapid growth, it is critical to guarantee their quality. So far, map validation has primarily focused on the agreement between maps and models. From the image processing perspective, the validation has been mostly restricted to using two half-maps and the measurement of their internal consistency. In this article, we suggest that map validation can be taken much further from the point of view of image processing if 2D classes, particles, angles, coordinates, defoci, and micrographs are also provided. We present a progressive validation scheme that qualifies a result validation status from 0 to 5 and offers three optional qualifiers (A, W, and O) that can be added. The simplest validation state is 0, while the most complete would be 5AWO. This scheme has been implemented in a website https://biocomp.cnb.csic.es/EMValidationService/ to which reconstructed maps and their ESI can be uploaded.

BIPSPI+: Mining Type-Specific Datasets of Protein Complexes to Improve Protein Binding Site Prediction.

Computational approaches for predicting protein-protein interfaces are extremely useful for understanding and modelling the quaternary structure of protein assemblies. In particular, partner-specific binding site prediction methods allow delineating the specific residues that compose the interface of protein complexes. In recent years, new machine learning and other algorithmic approaches have been proposed to solve this problem. However, little effort has been made in finding better training datasets to improve the performance of these methods. With the aim of vindicating the importance of the training set compilation procedure, in this work we present BIPSPI+, a new version of our original server trained on carefully curated datasets that outperforms our original predictor. We show how prediction performance can be improved by selecting specific datasets that better describe particular types of protein interactions and interfaces (e.g. homo/hetero). In addition, our upgraded web server offers a new set of functionalities such as the sequence-structure prediction mode, hetero- or homo-complex specialization and the guided docking tool that allows to compute 3D quaternary structure poses using the predicted interfaces. BIPSPI+ is freely available at https://bipspi.cnb.csic.es.

Cryo-EM and Single-Particle Analysis with Scipion.

Cryo-electron microscopy has become one of the most important tools in biological research to reveal the structural information of macromolecules at near-atomic resolution. In single-particle analysis, the vitrified sample is imaged by an electron beam and the detectors at the end of the microscope column produce movies of that sample. These movies contain thousands of images of identical particles in random orientations. The data need to go through an image processing workflow with multiple steps to obtain the final 3D reconstructed volume. The goal of the image processing workflow is to identify the acquisition parameters to be able to reconstruct the specimen under study. Scipion provides all the tools to create this workflow using several image processing packages in an integrative framework, also allowing the traceability of the results. In this article the whole image processing workflow in Scipion is presented and discussed with data coming from a real test case, giving all the details necessary to go from the movies obtained by the microscope to a high resolution final 3D reconstruction. Also, the power of using consensus tools that allow combining methods, and confirming results along every step of the workflow, improving the accuracy of the obtained results, is discussed.

Blockage of autophagic flux is associated with lymphocytosis and higher percentage of tumoral cells in chronic lymphocytic leukemia of B cells.

PURPOSE: Autophagy has lately emerged as an important biological process with implications in several hematological pathologies. Recently, a growing body of evidence supports a putative role of autophagy in chronic lymphocytic leukemia; however, no definitive clue has been established so far. To elucidate this issue, we have developed a pilot study to measure autophagic flux in peripheral blood mononuclear cells from chronic lymphocytic leukemia patients, and explored its correlation with classical clinical/analytical parameters. METHODS/PATIENTS: Thirty-three chronic lymphocytic leukemia patients participated in the study. Autophagic flux in peripheral blood mononuclear cells was determined by western blot measuring the levels of the proteins p62 and lipidated LC3. Moreover, p62 mRNA levels were analyzed by RT-qPCR. RESULTS: Lymphocytosis and the percentage of tumoral lymphocytes in chronic lymphocytic leukemia patients statistically correlate with a blocked autophagic flux. CONCLUSION: Alterations in autophagic flux could play an important role in the physiopathology of chronic lymphocytic leukemia.

Integrating electron microscopy information into existing Distributed Annotation Systems.

The increase of daily released bioinformatic data has generated new ways of organising and disseminating information. Specifically, in the field of sequence data, many efforts have been made not only to store information in databases, but also to annotate it and then share these annotations through a standard XML (eXtensible Markup Language) protocol and appropriate integration clients. This is the context in which the Distributed Annotation System (DAS) has emerged in genomics. Additionally, initiatives in the field of structural data, such as the extension of DAS to atomic resolution data, which generated the SPICE client, have also occurred. This paper presents 3D-EM DAS, a further extension of the DAS protocol that allows sharing annotations about hybrid models. This annotation system has been built on the basis of the EMDB, which stores Three-dimensional Electron Microscopy (3D-EM) volumes, PDB, which houses atomic coordinates, and UniProt (for protein sequences) databases. In this way, annotations for sequences, atomic coordinates, and 3D-EM volumes are collected and displayed through a single graphical visualization client. Thus, users have an integrated view of all the annotations together with the whole macromolecule (3D-EM map coming from EMDB), the atomic resolution structures fitted into it (coordinates coming from PDB) and the sequences corresponding to each of the structures (from UniProt).

Prevención de hematomas de pared abdominal cuando se emplean heparinas de bajo peso molecular / Prevention of abdominal wall hematomas in patients receiving low molecular weight heparin therapy

No disponible

No disponible

Leucemia linfoide aguda tras cáncer de mama y fiebre Q / Acute lymphocytic leukaemia following breast cancer and Q fever

No disponible

Cloning, sequencing and expression of the gene encoding elongation factor P in the amino-acid producer Brevibacterium lactofermentum (Corynebacterium glutamicum ATCC 13869).

The Brevibacterium lactofermentum EF-P gene, encoding the elongation factor protein P, was cloned and sequenced. According to DNA sequence analysis of this gene, the B. lactofermentum EF-P protein consists of 187 amino acids with a calculated molecular weight of 20,584. Southern hybridization of an internal fragment of the EF-P gene from B. lactofermentum with chromosomal DNAs from different microorganisms reveals that it is a unique gene product in B. lactofermentum and Corynebacterium glutamicum. The EF-P gene was expressed in E. coli using the T7 expression system and the calculated molecular weight of the expressed protein was 23,000. Disruption experiments using an internal fragment of the EF-P gene or a disrupted EF-P gene in suicide plasmids always failed, suggesting that the gene is needed for cell viability.

[Primary lung Kaposi sarcoma associated to AIDS in a heterosexual drug addict man]. / Sarcoma de Kaposi pulmonar primario asociado a SIDA en un varón heterosexual drogadicto.

A case of lung Kaposi sarcoma (KS) in the absence of cutaneomucosal lesions was observed in a 30-year-old heterosexual male with AIDS and a history of intravenous drug addiction. Both chest X-ray and CT scanning disclosed a diffuse nodular pattern in lungs, whereas endoscopy failed to demonstrate endobronchial damage. Cytological examination of the sample taken by transthoracic lung puncture proved compatible with primary KS, a rare neoplasia in heterosexual male drug addicts with AIDS. A year following the diagnosis of KS, the patient died of respiratory failure.

[Probable HIV transmission by female homosexual contact]. / Probable transmision de HIV por contacto homosexual femenino.

Here we report a case of HIV infection in a lesbian lacking other risk factors. She had sought advice for asthenia and unexplained weight loss. The physical examination disclosed oropharyngeal candidiasis and generalized lymphoadenopathies. The patient defined herself as an active sexual partner and denied having any heterosexual intercourse whatsoever. Particle agglutination test proved positive for anti-HIV, as well as two consecutive ELISA assays, confirmed by Western blot. Since there was no history of blood transfusions or intravenous drug addiction, it may be concluded that HIV transmission was most likely due to female homosexual practices.

Probable transmision de HIV por contacto homosexual femenino. / [Probable HIV transmission by female homosexual contact]

Here we report a case of HIV infection in a lesbian lacking other risk factors. She had sought advice for asthenia and unexplained weight loss. The physical examination disclosed oropharyngeal candidiasis and generalized lymphoadenopathies. The patient defined herself as an active sexual partner and denied having any heterosexual intercourse whatsoever. Particle agglutination test proved positive for anti-HIV, as well as two consecutive ELISA assays, confirmed by Western blot. Since there was no history of blood transfusions or intravenous drug addiction, it may be concluded that HIV transmission was most likely due to female homosexual practices.

Sarcoma de Kaposi/Sida en pacientes de sexo femenino: consideraciones a proposito de cinco casos / Kaposi's sarcoma in female sex patients considerations apropos of five cases

Se relatan cinco casos de sarcoma de Kaposi Sida en pacientes de sexo femenino. Se destaca que todas tuvieron lesiones en las mucosas accesibles; que dichas lesiones a veces precedieron a las cutaneas, que en ningno de los casos el contagio de Sida fue transfusional o por inyeccion de productos de sangre, y que en la mayoria de los casos el sarcoma de Kaposi aparece cuando el deterioro inmunologico ya es muy marcado, preanunciando un rapido desenlace fatal. Esto ultimo, en contraste con lo que sucede en el sexo masculino

Sarcoma de Kaposi/Sida en pacientes de sexo femenino: consideraciones a proposito de cinco casos / Kaposis sarcoma in female sex patients considerations apropos of five cases

Se relatan cinco casos de sarcoma de Kaposi Sida en pacientes de sexo femenino. Se destaca que todas tuvieron lesiones en las mucosas accesibles; que dichas lesiones a veces precedieron a las cutaneas, que en ningno de los casos el contagio de Sida fue transfusional o por inyeccion de productos de sangre, y que en la mayoria de los casos el sarcoma de Kaposi aparece cuando el deterioro inmunologico ya es muy marcado, preanunciando un rapido desenlace fatal. Esto ultimo, en contraste con lo que sucede en el sexo masculino(AU)

[Acute thoracic syndrome]. / Síndrome torácico agudo.

The acute chest syndrome is a clinical entity appearing in patients suffering from sickle cell anaemia. It presents with pleuritic pain, fever, leucocytosis and pulmonary infiltrates in the thoracic radiology. The etiological diagnosis is difficult, and it is necessary to distinguish between pneumonia and pulmonary infarction. This syndrome is quite frequent among the patients at risk, and can be lethal according to the severity and the etiology of the event. A case of acute chest syndrome due to a S. pneumoniae sepsis is presented. The interest of the case lies in the rareness of this disease in our population and the peculiar evolutive clinical features of this case, with the development of intracranial hypertension and death.

[Lymphomatous polyposis of the digestive tract]. / Poliposis linfomatosa del tubo digestivo.

A case of multiple lymphomatous polyposis of the gastrointestinal tract is presented. The recent literature on this type of lymphoma is reviewed. Also summarized are the clinical findings, diagnostic procedures, current methods of treatment and prognosis of these patients. Diarrhea upon admission, lead us to a complete work up finally to the correct diagnosis. The lack of symptoms of this patient was in contrast with most of the cases reviewed, so the diagnosis was mainly based on the endoscopic findings (colonoscopy and esofago-gastro-duodenoscopy). It is emphasized the importance of repeated biopsies in case of negative ones, as it occurs in this patient, in which an endoscopic "polypectomy" from the recto-sigmoid area, provided enough material to the pathologist, for the diagnosis, after several "non-diagnostic" biopsies taken previously. Finally the therapy for this entity is updated, with special reference to quemotherapy and a list of drugs combination is given.