52 research outputs found

    Comparative genomics of proteins involved in RNA nucleocytoplasmic export

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    Background: The establishment of the nuclear membrane resulted in the physical separation of transcription and translation, and presented early eukaryotes with a formidable challenge: how to shuttle RNA from the nucleus to the locus of protein synthesis. In prokaryotes, mRNA is translated as it is being synthesized, whereas in eukaryotes mRNA is synthesized and processed in the nucleus, and it is then exported to the cytoplasm. In metazoa and fungi, the different RNA species are exported from the nucleus by specialized pathways. For example, tRNA is exported by exportin-t in a RanGTP-dependent fashion. By contrast, mRNAs are associated to ribonucleoproteins (RNPs) and exported by an essential shuttling complex (TAP-p15 in human, Mex67-mtr2 in yeast) that transports them through the nuclear pore. The different RNA export pathways appear to be well conserved among members of Opisthokonta, the eukaryotic supergroup that includes Fungi and Metazoa. However, it is not known whether RNA export in the other eukaryotic supergroups follows the same export routes as in opisthokonts. Methods: Our objective was to reconstruct the evolutionary history of the different RNA export pathways across eukaryotes. To do so, we screened an array of eukaryotic genomes for the presence of homologs of the proteins involved in RNA export in Metazoa and Fungi, using human and yeast proteins as queries. Results: Our genomic comparisons indicate that the basic components of the RanGTP-dependent RNA pathways are conserved across eukaryotes, and thus we infer that these are traceable to the last eukaryotic common ancestor (LECA). On the other hand, several of the proteins involved in RanGTP-independent mRNA export pathways are less conserved, which would suggest that they represent innovations that appeared later in the evolution of eukaryotes. Conclusions: Our analyses suggest that the LECA possessed the basic components of the different RNA export mechanisms found today in opisthokonts, and that these mechanisms became more specialized throughout eukaryotic evolution

    Towards precision medicine: defining and characterizing adipose tissue dysfunction to identify early immunometabolic risk in symptom-free adults from the GEMM family study

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    Interactions between macrophages and adipocytes are early molecular factors influencing adipose tissue (AT) dysfunction, resulting in high leptin, low adiponectin circulating levels and low-grade metaflammation, leading to insulin resistance (IR) with increased cardiovascular risk. We report the characterization of AT dysfunction through measurements of the adiponectin/leptin ratio (ALR), the adipo-insulin resistance index (Adipo-IRi), fasting/postprandial (F/P) immunometabolic phenotyping and direct F/P differential gene expression in AT biopsies obtained from symptom-free adults from the GEMM family study. AT dysfunction was evaluated through associations of the ALR with F/P insulin-glucose axis, lipid-lipoprotein metabolism, and inflammatory markers. A relevant pattern of negative associations between decreased ALR and markers of systemic low-grade metaflammation, HOMA, and postprandial cardiovascular risk hyperinsulinemic, triglyceride and GLP-1 curves was found. We also analysed their plasma non-coding microRNAs and shotgun lipidomics profiles finding trends that may reflect a pattern of adipose tissue dysfunction in the fed and fasted state. Direct gene differential expression data showed initial patterns of AT molecular signatures of key immunometabolic genes involved in AT expansion, angiogenic remodelling and immune cell migration. These data reinforce the central, early role of AT dysfunction at the molecular and systemic level in the pathogenesis of IR and immunometabolic disorders

    Consenso Mexicano para el Tratamiento de la Hepatitis C

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    El objetivo del Consenso Mexicano para el Tratamiento de la Hepatitis C fue el de desarrollar un documento como guía en la práctica clínica con aplicabilidad en México. Se tomó en cuenta la opinión de expertos en el tema con especialidad en: gastroenterología, infectología y hepatología. Se realizó una revisión de la bibliografía en MEDLINE, EMBASE y CENTRAL mediante palabras claves referentes al tratamiento de la hepatitis C. Posteriormente se evaluó la calidad de la evidencia mediante el sistema GRADE y se redactaron enunciados, los cuales fueron sometidos a voto mediante un sistema modificado Delphi, y posteriormente se realizó revisión y corrección de los enunciados por un panel de 34 votantes. Finalmente se clasificó el nivel de acuerdo para cada oración. Esta guía busca dar recomendaciones con énfasis en los nuevos antivirales de acción directa y de esta manera facilitar su uso en la práctica clínica. Cada caso debe ser individualizado según sus comorbilidades y el manejo de estos pacientes siempre debe ser multidisciplinario. Abstract The aim of the Mexican Consensus on the Treatment of Hepatitis C was to develop clinical practice guidelines applicable to Mexico. The expert opinion of specialists in the following areas was taken into account: gastroenterology, infectious diseases, and hepatology. A search of the medical literature was carried out on the MEDLINE, EMBASE, and CENTRAL databases through keywords related to hepatitis C treatment. The quality of evidence was subsequently evaluated using the GRADE system and the consensus statements were formulated. The statements were then voted upon, using the modified Delphi system, and reviewed and corrected by a panel of 34 voting participants. Finally, the level of agreement was classified for each statement. The present guidelines provide recommendations with an emphasis on the new direct-acting antivirals, to facilitate their use in clinical practice. Each case must be individualized according to the comorbidities involved and patient management must always be multidisciplinary

    Reducing the environmental impact of surgery on a global scale: systematic review and co-prioritization with healthcare workers in 132 countries

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    Abstract Background Healthcare cannot achieve net-zero carbon without addressing operating theatres. The aim of this study was to prioritize feasible interventions to reduce the environmental impact of operating theatres. Methods This study adopted a four-phase Delphi consensus co-prioritization methodology. In phase 1, a systematic review of published interventions and global consultation of perioperative healthcare professionals were used to longlist interventions. In phase 2, iterative thematic analysis consolidated comparable interventions into a shortlist. In phase 3, the shortlist was co-prioritized based on patient and clinician views on acceptability, feasibility, and safety. In phase 4, ranked lists of interventions were presented by their relevance to high-income countries and low–middle-income countries. Results In phase 1, 43 interventions were identified, which had low uptake in practice according to 3042 professionals globally. In phase 2, a shortlist of 15 intervention domains was generated. In phase 3, interventions were deemed acceptable for more than 90 per cent of patients except for reducing general anaesthesia (84 per cent) and re-sterilization of ‘single-use’ consumables (86 per cent). In phase 4, the top three shortlisted interventions for high-income countries were: introducing recycling; reducing use of anaesthetic gases; and appropriate clinical waste processing. In phase 4, the top three shortlisted interventions for low–middle-income countries were: introducing reusable surgical devices; reducing use of consumables; and reducing the use of general anaesthesia. Conclusion This is a step toward environmentally sustainable operating environments with actionable interventions applicable to both high– and low–middle–income countries

    Induction of neutralizing antibodies against mutalysin-II from Lachesis muta muta Snake Venom Elicited by a conformational B-cell epitope predicted by Blue Star Sting data base.

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    Mutalysin-II, from Lachesis muta muta snake venom, is an endopeptidase with hemorrhagic activity. To identify a conformational epitope we used Blue Star Sting, the latest version of the web based Sting Millenium Suite, as alternative computational analysis tool to select and design peptides. Pre-selected cut-off values of the accessibility and hydrophilicity parameters were used to select amino acid residues as potential conformational epitopes. A peptide (P117-Y116-C115-Q194-C195-L197-N198-K199-P200-Y5-L48) was manually drawn on Swiss-PDB-Viewer package and synthesized by Fmoc-synthesis. Immunization of rabbits with this peptide induced antibodies that recognized Mutalysin-II and protected against the hemorrhagic factors present in Lachesis venom. The Sting Millennium Suite was able to predict conformational epitopes in this class of proteins. Three amino acids (K199, Y5 and L48) were identified as essential in the interaction between the peptide and the neutralizing antibodies

    Spatio-temporal variation in the diet composition of red lionfish, Pterois volitans (Actinopterygii: Scorpaeniformes: Scorpaenidae), in the Mexican Caribbean: Insights into the ecological effect of the alien invasion

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    Background. The observed expansion of the red lionfish, Pterois volitans  (Linnaeus, 1758), in the Caribbean represents one of the most rapid marine fish invasions in the history. The invasion rate of this top predator has resulted in a marked negative effect on local fish populations in the Caribbean by impacting local biodiversity. The main aim of this work was to conduct the morphological identification of prey items from the lionfish diet, and to determine the spatio--temporal variation of the lionfish diet composition in different sites of the Mexican Caribbean, to have a better knowledge of how this invasive species is impacting local species of commercial or ecological importance in the region. Materials and methods. The Mexican Caribbean study area was divided in three zones; North (one locality Isla Contoy), Central (three locations Xpu-Ha, Akumal and X’Cacel), and South (two locations Banco Chinchorro and Xcalak). The fish were collected, from different habitats, using SCUBA diving and Hawaiian harpoon. Collected fish were taxonomically identified, measured for total length (TL) and standard length (SL), and weighed to the nearest gram. Prey items were identified using a dissection microscope. After identification, prey items were separated, counted, and weighted individually. Finally, statistical analyses were made for all the samples using this study database, containing predators and prey items. Results. A total of 76 prey species were identified in 962 lionfish stomachs; 47 of them represented fishes and 29—crustaceans. Fishes of families Pomacentridae, Labridae, and Scaridae were the most abundant diet components of lionfish. Rhynchocinetidae, Penaeidae, and Solenoceridae were the most representative Crustaceans families among the prey items. Molluscs were present as diet components only as incidental food. Conclusion. Red lionfish, known for its high competitive capacity, preyed more intensively on fishes than on crustaceans. Therefore, it is evident that the lionfish presence in the Mexican Caribbean may affect mainly the local population of reef fishes. The presently reported results contribute to a better understanding of the red lionfish invasion in the Caribbean

    Upper gastrointestinal Dieulafoy's lesions and endoscopic treatment: First report from a Mexican centre

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    The aim was to evaluate the initial success, rebleeding rate, need for emergent surgery, and mortality rates of patients with Dieulafoy's lesion (DL) and endoscopic treatment (ET). Patients with DL from a tertiary center were included. We included 20 patients with follow-up of 90 (60—550) days. The lesser curvature was the most common localization. Initial success, rebleeding, and emergent surgery requirement were observed in 90%, 10%, and 15%, respectively. No objective variables were related with response to ET. In conclusion, ET is secure and useful in patients with DL and it must be considered as the first-line treatment modality

    Procesado de Imágenes de Microorganismos.

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    Debido a la diversidad de formas y tamaños que presentan tanto organismos vivientes como objetos inertes, ha surgido la importante necesidad de buscar sistemas automatizados de identificación. Dichos sistemas han sido utilizados en diversas aplicaciones, tanto en la industria como en el quehacer científico. El interés en desarrollar y utilizar nuevos sistemas ópticos y algoritmos digitales para el reconocimiento de organismos, independientemente de su escala, rotación y translación dentro una imagen, ha permitido la identificación de algunas especies de fitoplancton, zooplancton, bacterias (tuberculósis y Vibrio cholerae 01), cuerpos de inclusión de virus en imágenes de tejido de camarón (IHHN y WS), cromosomas del abulón rojo, azul y amarillo y parásitos de peces. Además, el problema de la captura de las imágenes en un sistema de identificación y clasificación automática de partículas biogénicas se circunscribe a dos aspectos fundamentales. El primero de ellos consiste en la localización automática de las partículas a identificar y segundo reside en la obtención del mejor plano focal de entre un conjunto de imágenes candidatas. Para lograr este último propósito, una posible solución al problema consiste en la aplicación de técnicas de fusión de imágenes, por medio de las cuales la imagen fusionada permita mostrar aquellas características ornamentales que se encuentran a diferentes planos focales y que permiten caracterizar las diferentes partículas biogénicas. Otra aplicación de sistemas ópticos-digitales, es el estudio de superficies marinas reales a partir de imágenes remotas. Cuando se tienen superficies con variaciones de altura y detalle lateral mucho mayor que la longitud de onda, la óptica geométrica es aplicable, siempre y cuando los efectos de esparcimiento múltiple sean despreciables, de esta forma a través de la utilización de nuevos algoritmos es posible describir el comportamiento de la superficie del mar, con aplicaciones en el ámbito costero
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