Aproximación teórica a la evolución de los endosimbiontes bacterianos de los áfidos

Tesis inédita de la Universidad Complutense de Madrid, Facultad de Ciencias Químicas, Departamento de Bioquímica y Biología Molecular, leída el 28/11/2019Los insectos parecen ser particularmente proclives a la convivencia con muy diversas bacterias con quienes establecen relaciones de muy variada índole. En particular, los endosimbiontes primarios se alojan en exclusiva en el interior de células especializadas del insecto denominadas bacteriocitos, se transmiten verticalmente a la descendencia, y establecen una relación de mutua dependencia con el hospedador. Las particularidades de los endosimbiontes primarios han probado ser valiosos modelos en el estudio de las características y consecuencias evolutivas de la transición de un modo de vida libre a uno de dependencia total de un hospedador. El genoma bacteriano sufre diversos cambios tras la transición a un estilo de vida intracelular que desencadenan una masiva inhabilitación y pérdida de genes que desembocan en la constitución de un genoma prácticamente mínimo. A la luz de los datos actuales, adaptación, degeneración y evolución neutral son mecanismos posibles que pueden condicionar esta característica reducción genómica. Entonces, ¿qué fuerzas evolutivas están detrás de las características genómicas observadas en los endosimbiontes de insectos?...Insects seem to be particularly prone to coexistence with very diverse bacteria with whom they establish very varied relationships. In particular, primary endosymbionts are housed exclusively within specialized insect cells called bacteriocytes, are transmitted vertically to offspring, and establish a mutually dependent relationship with the host. The characteristics of the primary endosymbionts have proven to be valuable models in the study of the evolutionary characteristics and consequences of the transition from a free lifestyle to one that is totally dependent on a host. The bacterial genome undergoes various changes after the transition to an intracellular lifestyle that triggers a massive disabling and loss of genes that lead to the constitution of a practically minimal genome. In the light of current data, adaptation, degeneration and neutral evolution are possible mechanisms that may condition this characteristic genomic reduction. So what evolutionary forces are behind the genomic characteristics observed in insect endosymbionts? ...Depto. de Bioquímica y Biología MolecularFac. de Ciencias QuímicasTRUEunpu

Colorectal cancer: from the genetic model to posttranscriptional regulation by noncoding RNAs

Colorectal cancer is the third most common form of cancer in developed countries and, despite the improvements achieved in its treatment options, remains as one of the main causes of cancer-related death. In this review, we first focus on colorectal carcinogenesis and on the genetic and epigenetic alterations involved. In addition, noncoding RNAs have been shown to be important regulators of gene expression. We present a general overview of what is known about these molecules and their role and dysregulation in cancer, with a special focus on the biogenesis, characteristics, and function of microRNAs. These molecules are important regulators of carcinogenesis, progression, invasion, angiogenesis, and metastases in cancer, including colorectal cancer. For this reason, miRNAs can be used as potential biomarkers for diagnosis, prognosis, and efficacy of chemotherapeutic treatments, or even as therapeutic agents, or as targets by themselves. Thus, this review highlights the importance of miRNAs in the development, progression, diagnosis, and therapy of colorectal cancer and summarizes current therapeutic approaches for the treatment of colorectal cancer

Mortality from gastrointestinal congenital anomalies at 264 hospitals in 74 low-income, middle-income, and high-income countries: a multicentre, international, prospective cohort study

Summary Background Congenital anomalies are the fifth leading cause of mortality in children younger than 5 years globally. Many gastrointestinal congenital anomalies are fatal without timely access to neonatal surgical care, but few studies have been done on these conditions in low-income and middle-income countries (LMICs). We compared outcomes of the seven most common gastrointestinal congenital anomalies in low-income, middle-income, and high-income countries globally, and identified factors associated with mortality. Methods We did a multicentre, international prospective cohort study of patients younger than 16 years, presenting to hospital for the first time with oesophageal atresia, congenital diaphragmatic hernia, intestinal atresia, gastroschisis, exomphalos, anorectal malformation, and Hirschsprung’s disease. Recruitment was of consecutive patients for a minimum of 1 month between October, 2018, and April, 2019. We collected data on patient demographics, clinical status, interventions, and outcomes using the REDCap platform. Patients were followed up for 30 days after primary intervention, or 30 days after admission if they did not receive an intervention. The primary outcome was all-cause, in-hospital mortality for all conditions combined and each condition individually, stratified by country income status. We did a complete case analysis. Findings We included 3849 patients with 3975 study conditions (560 with oesophageal atresia, 448 with congenital diaphragmatic hernia, 681 with intestinal atresia, 453 with gastroschisis, 325 with exomphalos, 991 with anorectal malformation, and 517 with Hirschsprung’s disease) from 264 hospitals (89 in high-income countries, 166 in middleincome countries, and nine in low-income countries) in 74 countries. Of the 3849 patients, 2231 (58·0%) were male. Median gestational age at birth was 38 weeks (IQR 36–39) and median bodyweight at presentation was 2·8 kg (2·3–3·3). Mortality among all patients was 37 (39·8%) of 93 in low-income countries, 583 (20·4%) of 2860 in middle-income countries, and 50 (5·6%) of 896 in high-income countries (p<0·0001 between all country income groups). Gastroschisis had the greatest difference in mortality between country income strata (nine [90·0%] of ten in lowincome countries, 97 [31·9%] of 304 in middle-income countries, and two [1·4%] of 139 in high-income countries; p≤0·0001 between all country income groups). Factors significantly associated with higher mortality for all patients combined included country income status (low-income vs high-income countries, risk ratio 2·78 [95% CI 1·88–4·11], p<0·0001; middle-income vs high-income countries, 2·11 [1·59–2·79], p<0·0001), sepsis at presentation (1·20 [1·04–1·40], p=0·016), higher American Society of Anesthesiologists (ASA) score at primary intervention (ASA 4–5 vs ASA 1–2, 1·82 [1·40–2·35], p<0·0001; ASA 3 vs ASA 1–2, 1·58, [1·30–1·92], p<0·0001]), surgical safety checklist not used (1·39 [1·02–1·90], p=0·035), and ventilation or parenteral nutrition unavailable when needed (ventilation 1·96, [1·41–2·71], p=0·0001; parenteral nutrition 1·35, [1·05–1·74], p=0·018). Administration of parenteral nutrition (0·61, [0·47–0·79], p=0·0002) and use of a peripherally inserted central catheter (0·65 [0·50–0·86], p=0·0024) or percutaneous central line (0·69 [0·48–1·00], p=0·049) were associated with lower mortality. Interpretation Unacceptable differences in mortality exist for gastrointestinal congenital anomalies between lowincome, middle-income, and high-income countries. Improving access to quality neonatal surgical care in LMICs will be vital to achieve Sustainable Development Goal 3.2 of ending preventable deaths in neonates and children younger than 5 years by 2030

Trabajo de grado realizado en el Centro de Vivienda Social "Cenvisocial"

114 páginasRESUMEN: El trabajo social como proyecto de Grado constituye un compromiso de la Escuela de Iriqenieria de Antioquia, sus alumnos y directivos para con las necesidades de las cl ases menos favorecidas. El ingeniero debe estar siempre conciente de la función social de su labor y comprometerse a dar todo de su parte intelectual y humana para aportar al desarrolla de su sociedad, en especial de las comunidades marginadas que necesitan de mayor atención y cuyas necesidades se tornan más cri ticos. El trabajo que a continuación se presenta -Fue desarrollado para el centro de vivienda social Cenvisocial , institución de la congregación mariana, Fundada en Medel 1 i' n a finales de 1986.. En colaboración con el gremio de la construcción de Cenvisoc:ial son proporcionar a la comunidad marginada y de escasos recursos economi cas asesor ja en la relacionada con :La vivienda construcción, remodelación, mejoram:iento, legalización, etc. , para la cual presta asesan a en la adquisición de lotes, elaboración de di senos y planos i3rqui tc:tcini c:cs y/o estructurales, 'i.¿abrirac:ic5n de presupuestos, asesorias especial iz adas en problemas suelos, aguas, legalización ante entidades oficiales, etc . Trabajo en coordinación con otras entidades de caracter oficial o privado en busca de la solución integral del problema de vivienda popular.PregradoIngeniero(a) Civi

Pervasive conditional selection of driver mutations and modular epistasis networks in cancer

23 Pág. Centro de Biotecnología y Genómica de PlantasCancer driver mutations often display mutual exclusion or co-occurrence, underscoring the key role of epistasis in carcinogenesis. However, estimating the magnitude of epistasis and quantifying its effect on tumor evolution remains a challenge. We develop a method (Coselens) to quantify conditional selection on the excess of nonsynonymous substitutions in cancer genes. Coselens infers the number of drivers per gene in different partitions of a cancer genomics dataset using covariance-based mutation models and determines whether coding mutations in a gene affect selection for drivers in any other gene. Using Coselens, we identify 296 conditionally selected gene pairs across 16 cancer types in the TCGA dataset. Conditional selection affects 25%-50% of driver substitutions in tumors with >2 drivers. Conditionally co-selected genes form modular networks, whose structures challenge the traditional interpretation of within-pathway mutual exclusivity and across-pathway synergy, suggesting a more complex scenario where gene-specific across-pathway epistasis shapes differentiated cancer subtypes.J.I. is supported by the Ramón y Cajal Program of the Spanish Ministry of Science (grant no. RYC-2017-22524), the Agencia Estatal de Investigación of Spain (grant no. PID2019-106618GA-I00), and the Severo Ochoa Program for Centers of Excellence in R&D of the Agencia Estatal de Investigación of Spain (grant no. SEV-2016-0672 [2017–2021] to the CBGP). G.G. is supported by the DHHS/PHS/National Institutes of Health (grant no. 2R01DE019637-10, “Patterning the vertebrate dentition through replacement and repair”). J.C.-E. is supported by the Youth Employment Initiative of the European Social Fund through a junior postdoctoral contract from Comunidad de Madrid (grant no. PEJD-2019-POST/BIO-16377). E.V.K. is supported by intramural research program funds of the National Institutes of Health (National Library of Medicine).Peer reviewe

Protocol for comparing gene-level selection on coding mutations between two groups of samples with Coselens

19 Pág.The study of genes that evolve under conditional selection can shed light on the genomic underpinnings of adaptation, revealing epistasis and phenotypic plasticity. This protocol describes how to use the Coselens package to compare gene-level selection between two groups of samples. After installing Coselens and preparing the datasets, a typical run on a laptop takes less than 10 min. Coselens is best suited to analyze somatic mutations and data from experimental evolution, for which independently evolved samples are available. For complete details on the use and execution of this protocol, please refer to Iranzo et al. (2022).1.J.I. is supported by the Agencia Estatal de Investigación of Spain (Grant No. PID2019-106618GA-I00), the Ramón y Cajal Programme of the Spanish Ministry of Science (Grant No. RYC-2017-22524), the Severo Ochoa Programme for Centres of Excellence in R&D of the Agencia Estatal de Investigación of Spain (Grant No. CEX2020-000999-S (2022–2025) to the C.B.G.P.), and the Comunidad de Madrid (through the call Research Grants for Young Investigators from Universidad Politécnica de Madrid, Grant No. M190020074JIIS). G.G. is supported by the DHHS/PHS/National Institutes of Health (Grant No. 2R01DE019637-10, “Patterning the vertebrate dentition through replacement and repair). J.C.-E. is supported by the Youth Employment Initiative of the European Social Fund through a junior postdoctoral contract from Comunidad de Madrid (Grant No. PEJD-2019-POST/BIO-16377) and the Margarita Salas program of the Ministry of Universities of Spain (CT31/21). E.V.K. is supported by intramural research program funds of the National Institutes of Health (National Library of Medicine).With funding from the Spanish government through the ‘Severo Ochoa Centre of Excellence’ accreditation (CEX2020‐000999‐S)Peer reviewe

Consistency Analysis of Genome-Scale Models of Bacterial Metabolism: A Metamodel Approach.

Genome-scale metabolic models usually contain inconsistencies that manifest as blocked reactions and gap metabolites. With the purpose to detect recurrent inconsistencies in metabolic models, a large-scale analysis was performed using a previously published dataset of 130 genome-scale models. The results showed that a large number of reactions (~22%) are blocked in all the models where they are present. To unravel the nature of such inconsistencies a metamodel was construed by joining the 130 models in a single network. This metamodel was manually curated using the unconnected modules approach, and then, it was used as a reference network to perform a gap-filling on each individual genome-scale model. Finally, a set of 36 models that had not been considered during the construction of the metamodel was used, as a proof of concept, to extend the metamodel with new biochemical information, and to assess its impact on gap-filling results. The analysis performed on the metamodel allowed to conclude: 1) the recurrent inconsistencies found in the models were already present in the metabolic database used during the reconstructions process; 2) the presence of inconsistencies in a metabolic database can be propagated to the reconstructed models; 3) there are reactions not manifested as blocked which are active as a consequence of some classes of artifacts, and; 4) the results of an automatic gap-filling are highly dependent on the consistency and completeness of the metamodel or metabolic database used as the reference network. In conclusion the consistency analysis should be applied to metabolic databases in order to detect and fill gaps as well as to detect and remove artifacts and redundant information

Workflow diagram of the gap-filling process.

<p>The set of blocked is classified either as non-metablocked or Metablocked. Metablocked (red) reactions are the ones that couldn't be curated on the metamodel and thus are excluded or removed from the models. Non-metablockeds, are reactions found blocked in at least one GSM but actives in the metamodel and thus can be curated in the GSM. gap-filling reactions (green) are the set of reactions that need to be added to a model in order to unblocked the complete set of blocked non-metablocked. Finally, some of the gap-filling reactions can be associated to one or more genes (mapped) whereas others remain orphans.</p

Three examples of pathways unblocked as a consequences of the metamodel construction.

<p>In a) a partial representation of the aerobic degradation of catechol is depicted (metabolites in circles were manually added to clarify the diagram). In b) the import of choline sulfate is shown as an example of an in-to-out linear pathway artifact. In c) an example of an artifact is shown, with a set of reactions corresponding to two different variants of the adenosylcobalamin biosynthetic pathway: early cobalt insertion (right side); late cobalt incorporation (left side). Cofactors and currency metabolites were excluded from this representation. Metabolite abbreviations can be found in <a href="http://www.plosone.org/article/info:doi/10.1371/journal.pone.0143626#pone.0143626.s008" target="_blank">S3C Table</a>.</p