Data mining identifies novel RNA-binding proteins involved in colon and rectal carcinomas

Colorectal adenocarcinoma (COREAD) is the second most deadly cancer and third most frequently encountered malignancy worldwide. Despite efforts in molecular subtyping and subsequent personalized COREAD treatments, multidisciplinary evidence suggests separating COREAD into colon cancer (COAD) and rectal cancer (READ). This new perspective could improve diagnosis and treatment of both carcinomas. RNA-binding proteins (RBPs), as critical regulators of every hallmark of cancer, could fulfill the need to identify sensitive biomarkers for COAD and READ separately. To detect new RBPs involved in COAD and READ progression, here we used a multidata integration strategy to prioritize tumorigenic RBPs. We analyzed and integrated 1) RBPs genomic and transcriptomic alterations from 488 COAD and 155 READ patients, 2) ∼ 10,000 raw associations between RBPs and cancer genes, 3) ∼ 15,000 immunostainings, and 4) loss-of-function screens performed in 102 COREAD cell lines. Thus, we unraveled new putative roles of NOP56, RBM12, NAT10, FKBP1A, EMG1, and CSE1L in COAD and READ progression. Interestingly, FKBP1A and EMG1 have never been related with any of these carcinomas but presented tumorigenic features in other cancer types. Subsequent survival analyses highlighted the clinical relevance of FKBP1A, NOP56, and NAT10 mRNA expression to predict poor prognosis in COREAD and COAD patients. Further research should be performed to validate their clinical potential and to elucidate their molecular mechanisms underlying these malignancies

Relação de percepção de risco e consumo de álcool por adolescentes

El propósito del estudio fue conocer la relación entre percepción de riesgo y el consumo de alcohol en adolescentes de preparatoria. El estudio fue descriptivo, correlacional. El muestreo fue probabilístico, estratificado por semestre con asignación proporcional al tamaño de cada estrato, con una muestra de 345 adolescentes. Se utilizó una Cédula de identificación, el Cuestionario de Percepción de Riesgo hacia el Consumo de Alcohol y el instrumento AUDIT. De acuerdo a los resultados, se identificó una relación negativa significativa entre el índice de percepción de riesgo con el índice de AUDIT (rs= -.418, p=.001). Se concluye que a mayor percepción de riesgo, menor será el consumo de alcohol por parte de los adolescentes.O propósito do estudo foi conhecer a relação entre percepção de risco e o consumo de álcool por adolescentes do ensino médio. O estudo foi descritivo, correlacional. A amostragem foi probabilística, estratificada por semestre com distribuição proporcional ao tamanho de cada estrato, com uma amostra de 345 adolescentes. Utilizou-se uma ficha de identificação, um questionário de percepção de risco sobre o consumo de álcool e o instrumento AUDIT. De acordo com os resultados, identificou-se uma relação negativa significativa entre o índice de percepção de risco e o índice AUDIT (rs= -.418, p=.001). Conclui-se que quanto maior for a percepção de risco, menor será o consumo de álcool por parte dos adolescentes.The aim of the study was to discover the relationship between risk perception and alcohol consumption in adolescents in high school. This was a descriptive, correlational study. The sample was probabilistic, stratified by semester with allocation proportional to the size of each stratum, in a sample of 345 adolescents. We used identity cards, the Alcohol Risk Perception Questionnaire and the AUDIT instrument. The results showed a significant negative relationship between the risk perception rate and the AUDIT (rs= -.418, p=.001). We can conclude that the higher the perceived risk, the lower the alcohol consumption among adolescents

Cytogenetic and genomic analysis of a patient with turner syndrome and t(2;12): a case report

Background: Turner syndrome is a genetic disorder that afects women. It is caused by an absent or incomplete X chromosome, which can be presented in mosaicism or not. There are 12 cases of Turner syndrome patients who present structural alterations in autosomal chromosomes. Case presentation: The present case report describes a patient with a reciprocal, maternally inherited translocation between chromosomes 2 and 12 with a mosaicism of X monosomy 45,X,t(2;12)(p13;q24)[95]/46,XX,t(2;12)(p13;q24) [5]. Through genetic mapping arrays, altered genes in the patient were determined within the 23 chromosome pairs. These genes were associated with the patient’s clinical features using a bioinformatics tool Conclusion: To our knowledge, this is the frst case in which a translocation (2;12) is reported in a patient with Turner syndrome and confrmed by conventional cytogenetics, FISH and molecular genetics. Clinical features of our patient are closely related with the loss of one X chromosome, however mild intellectual disability can be likely explained by autosomal genes. The presence of familial translocations was a common fnding, thus emphasizing the need for familiar testing for further genetic counselling

A Quick Guide for Using Microsoft Onenote as an Electronic Laboratory Notebook

[Abstract] Scientific data recording and reporting systems are of a great interest for endorsing reproducibility and transparency practices among the scientific community. Current research generates large datasets that can no longer be documented using paper lab notebooks (PLNs). In this regard, electronic laboratory notebooks (ELNs) could be a promising solution to replace PLNs and promote scientific reproducibility and transparency. We previously analyzed five ELNs and performed two survey-based studies to implement an ELN in a biomedical research institute. Among the ELNs tested, we found that Microsoft OneNote presents numerous features related to ELN best functionalities. In addition, both surveyed groups preferred OneNote over a scientifically designed ELN (PerkinElmer Elements). However, OneNote remains a general note-taking application and has not been designed for scientific purposes. We therefore provide a quick guide to adapt OneNote to an ELN workflow that can also be adjusted to other nonscientific ELNs

USO DE MICROSOFT ONENOTE COMO CUADERNO ELECTRÓNICO DE LABORATORIO

Los sistemas de registro y de reporte de datos son de gran interés, puesto que respaldan la reproducibilidad y transparencia científica. La investigación actual genera una gran cantidad de datos que ya no se pueden documentar utilizando cuadernos de laboratorio de papel (CLP). Los cuadernos electrónicos de laboratorio (CEL) podrían ser una solu-ción prometedora para reemplazar los CLP y promover la reproducibilidad científica y su transparencia. Anteriormente analizamos cinco CEL y realizamos dos encuestas para implementar un CEL en un instituto de investigación biomédica. Entre los CEL proba-dos, encontramos que Microsoft OneNote presenta numerosas características relacio-nadas con las mejores funcionalidades del CEL. Además, ambos grupos encuestados prefirieron OneNote sobre un CEL científico (Elements de PerkinElmer). Sin embargo, OneNote es una aplicación general para tomar notas que no ha sido diseñada para fi-nes científicos. Por lo tanto, en este trabajo proporcionamos varias pautas para adaptar OneNote a un flujo de trabajo experimental

Inherited chromosomally integrated human herpesvirus 6 genomes are ancient, intact and potentially able to reactivate from telomeres

The genomes of human herpesviruses 6A and 6B (HHV-6A and HHV-6B) have the capacity to integrate into telomeres, the essential capping structures of chromosomes that play roles in cancer and ageing. About 1% of people worldwide are carriers of chromosomally integrated HHV-6 (ciHHV-6), which is inherited as a genetic trait. Understanding the consequences of integration for the evolution of the viral genome, for the telomere and for the risk of disease associated with carrier status is hampered by a lack of knowledge about ciHHV-6 genomes. Here, we report an analysis of 28 ciHHV-6 genomes and show that they are significantly divergent from the few modern non-integrated HHV-6 strains for which complete sequences are currently available. In addition ciHHV-6B genomes in Europeans are more closely related to each other than to ciHHV-6B genomes from China and Pakistan, suggesting regional variation of the trait. Remarkably, at least one group of European ciHHV-6B carriers has inherited the same ciHHV-6B genome, integrated in the same telomere allele, from a common ancestor estimated to have existed 24,500 ±10,600 years ago. Despite the antiquity of some, and possibly most, germline HHV-6 integrations, the majority of ciHHV-6B (95%) and ciHHV-6A (72%) genomes contain a full set of intact viral genes and therefore appear to have the capacity for viral gene expression and full reactivation. IMPORTANCE: Inheritance of HHV-6A or HHV-6B integrated into a telomere occurs at a low frequency in most populations studied to date but its characteristics are poorly understood. However, stratification of ciHHV-6 carriers in modern populations due to common ancestry is an important consideration for genome-wide association studies that aim to identify disease risks for these people. Here we present full sequence analysis of 28 ciHHV-6 genomes and show that ciHHV-6B in many carriers with European ancestry most likely originated from ancient integration events in a small number of ancestors. We propose that ancient ancestral origins for ciHHV-6A and ciHHV-6B are also likely in other populations. Moreover, despite their antiquity, all of the ciHHV-6 genomes appear to retain the capacity to express viral genes, and most are predicted to be capable of full viral reactivation. These discoveries represent potentially important considerations in immune-compromised patients, in particular in organ transplantation and in stem cell therapy

Analysis of Efflux Pump Genes in β-lactam Resistant Clinical Isolates of Pseudomonas aeruginosa from a Tertiary Level Hospital in Ecuador

Pseudomonas aeruginosa is a nosocomial microorganism that causes a wide spectrum of infections and is known as one of the primary multi-resistant microorganisms against β-lactam antibiotics. One of the main resistance mechanisms found in P. aeruginosa is the efflux pumps. This study is aimed at characterizing this mechanism by analyzing the expression of four genes (mexA, mexX, oprJ and oprM) involved in antibiotic efflux pumps in Pseudomonas aeruginosa. Forty clinical isolates (20 resistant, 20 susceptible) were collected from the Bacteriology Laboratory at the Carlos Andrade Marin Hospital, in Quito-Ecuador. Expression levels for the selected genes were assessed by RT-qPCR assays using RpsL as a housekeeping gene for ΔΔCt adjusted relative quantitation analysis. The importance of efflux pumps as a resistance mechanism was corroborated through analysis of efflux pumps genes that showed overexpression in all phenotypically resistant isolates. Furthermore, phenotype/genotype analysis was performed comparing Antibiotic Susceptibility Testing (AST) results with expression profiles. Results for the mexA genotype showed correlation with the TPZ resistance phenotype and the mexX genotype with the IPM, MEM and FEP resistance phenotypes. In conclusion, the expression pattern of the efflux pump genes suggests resistance mechanisms that are due to horizontal transmission or pathogens spreading into the hospital environment.Pseudomonas aeruginosa es un microorganismo responsable de una amplia variedad de infecciones y es uno de los principales patógenos multiresistentes ante antibióticos β-lactámicos. Uno de los principales mecanismos de resistencia en P. aeruginosa constituyen las bombas de eflujo. El objetivo del presente estudio fue caracterizar el mecanismo de bombas de eflujo mediante el estudio de expresión de 4 genes (mexA, mexX, oprJ y oprM) involucrados en este mecanismo en Pseudomonas aeruginosa. Cuarenta aislados clínicos (20 resistentes y 20 sensibles) fueron recolectados en el Laboratorio de Bacteriología del Hospital “Carlos Andrade Marin” en Quito-Ecuador. Los niveles de expression de los genes seleccionados fueron evaluados por RT-qPCR usando RpsL como gen constitutivo para el análisis de cuantificación relativa basado en el método ΔΔCt ajustado. La importancia de las bombas de eflujo como mecanismos de resistencia fue confirmada ya que el estudio de expresión de los genes relacionados con bombas de eflujo mostró sobreexpresión de ellos en todos los aislados fenotípicamente resistentes. Se realizó además un análisis fenotipo/genotipo comparando los resultados del antibiograma (AST) con los perfiles de expresión. La sobreexpresión de mexA (genotipo) mostró correlación con el fenotipo de resistencia a TPZ, mientras que el genotipo mexX se correlacionó con los fenotipos de resistencia a IPM, MEM y FEP. En conclusion, los patrones de expression de los genes relacionados con bombas de eflujo sugieren la presencia de mecanismos de resistencia basados en transmisión horizontal que posibilitan la diseminación de patógenos en el ambiente hospitalario

Identification of Key Proteins from the Alternative Lengthening of Telomeres-Associated Promyelocytic Leukemia Nuclear Bodies Pathway

Alternative lengthening of telomeres-associated promyelocytic leukemia nuclear bodies (APBs) are a hallmark of telomere maintenance. In the last few years, APBs have been described as the main place where telomeric extension occurs in ALT-positive cancer cell lines. A different set of proteins have been associated with APBs function, however, the molecular mechanisms behind their assembly, colocalization, and clustering of telomeres, among others, remain unclear. To improve the understanding of APBs in the ALT pathway, we integrated multiomics analyses to evaluate genomic, transcriptomic and proteomic alterations, and functional interactions of 71 APBs-related genes/proteins in 32 Pan-Cancer Atlas studies from The Cancer Genome Atlas Consortium (TCGA). As a result, we identified 13 key proteins which showed distinctive mutations, interactions, and functional enrichment patterns across all the cancer types and proposed this set of proteins as candidates for future ex vivo and in vivo analyses that will validate these proteins to improve the understanding of the ALT pathway, fill the current research gap about APBs function and their role in ALT, and be considered as potential therapeutic targets for the diagnosis and treatment of ALT-positive cancers in the future

Integrated in silico analyses identify PUF60 and SF3A3 as new spliceosome-related breast cancer RNA-binding proteins

More women are diagnosed with breast cancer (BC) than any other type of cancer. Although large-scale efforts have completely redefined cancer, a cure remains unattainable. In that respect, new molecular functions of the cell should be investigated, such as post-transcriptional regulation. RNA-binding proteins (RBPs) are emerging as critical post-transcriptional modulators of tumorigenesis, but only a few have clear roles in BC. To recognize new putative breast cancer RNA-binding proteins, we performed integrated in silico analyses of all human RBPs (n = 1392) in three major cancer databases and identified five putative BC RBPs (PUF60, TFRC, KPNB1, NSF, and SF3A3), which showed robust oncogenic features related to their genomic alterations, immunohistochemical changes, high interconnectivity with cancer driver genes (CDGs), and tumor vulnerabilities. Interestingly, some of these RBPs have never been studied in BC, but their oncogenic functions have been described in other cancer types. Subsequent analyses revealed PUF60 and SF3A3 as central elements of a spliceosome-related cluster involving RBPs and CDGs. Further research should focus on the mechanisms by which these proteins could promote breast tumorigenesis, with the potential to reveal new therapeutic pathways along with novel drug-development strategies.This research received no external fundin