Drosophila melanogaster com a organisme model: una font d'informació en recerca biomèdica

Drosophila melanogaster és un exemple d'organisme model des de fa més de cent anys. S'ha utilitzat des d'aleshores com a sistema per investigar alguns dels principis fonamentals de la genètica, la biologia molecular, l'enginyeria genètica, la biologia del desenvolupament i l'evolució. Però en les darreres dècades, Drosophila ha esdevingut un element clau com a font d'informació per entendre les bases genètiques en la recerca biomèdica. En aquest article discutirem alguns exemples de l'ús d'aquest organisme model.Drosophila melanogaster as a model system: a source of information for biomedical research. Drosophila melanogaster is an example of model organism since a hundred years ago. It has been used as a model system to investigate the basic principles of genetics, molecular biology, genetic engineering, developmental biology and evolution. But in the last decades, Drosophila has become key for the understanding of the genetic basis of diseases in biomedical research. In this article we will discuss some of the relevant features of Drosophila as model organism

Efficacy and safety of Pegylated Interferon-α2b Plus Ribavirin for the treatment of chronic hepatitis C in HIV-infected patients

Low response rates and concerns about safety have limited the implementation of treatment for chronic hepatitis C (CHC) in patients with HIV infection. The efficacy and safety of pegylated interferon (peg-IFN) plus ribavirin in HIV-infected patients with CHC were evaluated in a prospective, open-label, multicenter study. Sixty patients with persistently high transaminases, positive HCV-RNA, CD4 count ≥300 cells/µl, and HIVRNA <10,000 copies/ml were included. Patients were given peg-IFN 80-150 µg/week plus ribavirin 800-1200 mg/day. Treatment was scheduled for 24 weeks for genotypes 2/3 and 48 weeks for genotypes 1/4. In an intent- to-treat analysis, 16 (26.7%) patients achieved a sustained virological response (SVR). Twenty patients (33.3%) discontinued treatment prematurely, but only in 10 (16.6%) was discontinuation due to adverse events. Negative predictive values for SVR on the basis of HCV-RNA decline between baseline and week 4 were 100% for 1- and 2-log10 fall, and positive predictive values were 40% and 58.3% for 1- and 2-log10 fall, respectively. CD4 fell by a median of 216 cells during treatment, but no HIV-associated complications occurred. In conclusion, treatment with peg-IFN alfa-2b plus ribavirin is safe and clears RNA-HCV in about one-quarter of HIV-infected patients with CHC. Efforts should be focused on optimizing management of side effects and counseling to improve adherence and to keep patients on treatment. Assessment of HCV-RNA at week 4 may help guide early therapeutic decision making

COVID-19 symptoms at hospital admission vary with age and sex: results from the ISARIC prospective multinational observational study

Background: The ISARIC prospective multinational observational study is the largest cohort of hospitalized patients with COVID-19. We present relationships of age, sex, and nationality to presenting symptoms. Methods: International, prospective observational study of 60 109 hospitalized symptomatic patients with laboratory-confirmed COVID-19 recruited from 43 countries between 30 January and 3 August 2020. Logistic regression was performed to evaluate relationships of age and sex to published COVID-19 case definitions and the most commonly reported symptoms. Results: ‘Typical’ symptoms of fever (69%), cough (68%) and shortness of breath (66%) were the most commonly reported. 92% of patients experienced at least one of these. Prevalence of typical symptoms was greatest in 30- to 60-year-olds (respectively 80, 79, 69%; at least one 95%). They were reported less frequently in children (≤ 18 years: 69, 48, 23; 85%), older adults (≥ 70 years: 61, 62, 65; 90%), and women (66, 66, 64; 90%; vs. men 71, 70, 67; 93%, each P &lt; 0.001). The most common atypical presentations under 60 years of age were nausea and vomiting and abdominal pain, and over 60 years was confusion. Regression models showed significant differences in symptoms with sex, age and country. Interpretation: This international collaboration has allowed us to report reliable symptom data from the largest cohort of patients admitted to hospital with COVID-19. Adults over 60 and children admitted to hospital with COVID-19 are less likely to present with typical symptoms. Nausea and vomiting are common atypical presentations under 30 years. Confusion is a frequent atypical presentation of COVID-19 in adults over 60 years. Women are less likely to experience typical symptoms than men

La maleta avaluadora: Un prototip d’avaluació innovadora

L’avaluació és una part important en l’educació, que al llarg del temps ha anat patint petites modificacions. No és un procés tancat i es susceptible a innovació i com tots els processos cal enfocar-los des d’una perspectiva nova per a poder innovar. En aquest treball final de màster (TFM, en endavant) es presenta la creació de LA MALETA AVALUADORA: Un prototip d’avaluació innovadora. S’expliquen les bases del projecte que són l’avaluació, el disseny i la construcció d’una nova eina educativa centrada en els alumnes i posant especial atenció a la motivació com a eix vertebrador. Es construeix el projecte al voltant d’oferir una avaluació de qualitat, individual, puntual i motivadora en que el joc no serà la meta sinó una eina per a canviar l’actitud dels alumnes en front l’avaluació. No s’aprofundeix en què preguntar, sinó en la manera com es presenten les preguntes per a que cada estudiant tregui el seu màxim potencial. En definitiva, una eina d’avaluació innovadora i motivadora que ofereix una gran alternativa als exàmens tradicionals i que permet superar les limitacions mentals que aquests generen. Una avaluació engrescadora i divertida és possible!La evaluación es una parte importante en la educación, que a lo largo del tiempo ha ido sufriendo pequeñas modificaciones. No es un proceso cerrado y es susceptible a innovación y como todos los procesos hace falta enfocar-los desde una perspectiva nueva para poder innovar. En este trabajo final de máster (TFM, en adelante) se presenta la creación de LA MALETA EVALUADORA: Un prototipo de evaluación innovadora. Se explican las bases del proyecto que son la evaluación, el diseño i la construcción de una nueva herramienta educativa centrada en los alumnos y poniendo especial atención a la motivación como eje vertebrador. Se construye el proyecto alrededor de ofrecer una evaluación de calidad, individual, puntual y motivadora donde el juego no será una meta sino una herramienta para cambiar la actitud de les alumnos en frente a una evaluación. No se profundiza en que preguntar, sino que en la manera en cómo se presentan las preguntas para que cada estudiante saque su máximo potencial. En definitiva, una herramienta de evaluación innovadora i motivadora que ofrece una gran alternativa a los exámenes tradicionales y que permite superar las limitaciones mentales que estos generan. Una evaluación motivadora y divertida es posible.Assessment is an important part of Education, which over time has undergone small changes. It is not a closed process and is susceptible to innovation and like all processes it is necessary to approach them from a new perspective in order to innovate. This final master’s thesis (TFM, hereinafter) presents the creation of THE EVALUATION SUITCASE: A prototype of innovative evaluation. The basics of the project are explained, which are the evaluation, design and construction of a new educational tool focused on students and paying special attention to motivation as the backbone. The project is built around offering a quality, individual, timely and motivating assessment in which the game will not be the goal but a tool to change the attitude of students towards the assessment. It’s not about what to ask, it’s about how the questions are presented so that each student can reach their full potential. In short, an innovative and motivating assessment tool that offers a great alternative to traditional exams and allows you to overcome the mental limitations that these generate. An exciting and fun evaluation is possible

Control genético del desarrollo de los segmentos de "Drosophila"

Tesis Doctoral inédita leída en la Universidad Autónoma de Madrid. Facultad de Ciencias, Departamento de Biología Molecular. Fecha de lectura 28-05-198

Specific GATA factors act as conserved inducers of an endodermal-EMT

The epithelial-to-mesenchymal transition (EMT) converts cells from static epithelial to migratory mesenchymal states (Hay, 1995). Here, we demonstrate that EMT in the Drosophila endoderm is dependent on the GATA-factor Serpent (Srp), and that Srp acts as a potent trigger for this transition when activated ectopically. We show that Srp affects endodermal-EMT through a downregulation of junctional dE-Cadherin (dE-Cad) protein, without a block in its transcription. Moreover, the relocalization of dE-Cad is achieved through the direct repression of crumbs (crb) by Srp. Finally, we show that hGATA-6, an ortholog of Srp, induces a similar transition in mammalian cells. Similar to Srp, hGATA-6 acts through the downregulation of junctional E-Cad, without blocking its transcription, and induces the repression of a Crumbs ortholog, crb2. Together, these results identify a set of GATA factors as a conserved alternative trigger to repress epithelial characteristics and confer migratory capabilities on epithelial cells in development and pathogenesis.This work has been supported by the Generalitat de Catalunya, the Spanish Ministerio de Ciencia e Innovacion (MICINN) and its Consolider-Ingenio 2010 program to J.C., X.F.-M., and E.B. We also acknowledge support from the Programa Juan de la Cierva (K.C.) and the European Research/nCouncil (ERC-FP7) (E.B.

Quorum sensing network in clinical strains of A. baumannii : AidA is a new quorum quenching enzyme

Acinetobacter baumannii is an important pathogen that causes nosocomial infections generally associated with high mortality and morbidity in Intensive Care Units (ICUs). Currently, little is known about the Quorum Sensing (QS)/Quorum Quenching (QQ) systems of this pathogen. We analyzed these mechanisms in seven clinical isolates of A. baumannii. Microarray analysis of one of these clinical isolates, Ab1 (A. baumannii ST-2-clon-2010), previously cultured in the presence of 3-oxo-C12-HSL (a QS signalling molecule) revealed a putative QQ enzyme (α/β hydrolase gene, AidA). This QQ enzyme was present in all nonmotile clinical isolates (67% of which were isolated from the respiratory tract) cultured in nutrient depleted LB medium. Interestingly, this gene was not located in the genome of the only motile clinical strain growing in this medium (A. baumannii strain Ab421-GEIH-2010 [Ab7], isolated from a blood sample). The AidA protein expressed in E. coli showed QQ activity. Finally, we observed downregulation of the AidA protein (QQ system attenuation) in the presence of HO (ROS stress). In conclusion, most of the A. baumannii clinical strains were not surface motile (84%) and were of respiratory origin (67%). Only the pilT gene was involved in surface motility and related to the QS system. Finally, a new QQ enzyme (α/β hydrolase gene, AidA protein) was detected in these strains

Respiratory support in patients with severe COVID-19 in the International Severe Acute Respiratory and Emerging Infection (ISARIC) COVID-19 study: a prospective, multinational, observational study

Background: Up to 30% of hospitalised patients with COVID-19 require advanced respiratory support, including high-flow nasal cannulas (HFNC), non-invasive mechanical ventilation (NIV), or invasive mechanical ventilation (IMV). We aimed to describe the clinical characteristics, outcomes and risk factors for failing non-invasive respiratory support in patients treated with severe COVID-19 during the first two years of the pandemic in high-income countries (HICs) and low middle-income countries (LMICs). Methods: This is a multinational, multicentre, prospective cohort study embedded in the ISARIC-WHO COVID-19 Clinical Characterisation Protocol. Patients with laboratory-confirmed SARS-CoV-2 infection who required hospital admission were recruited prospectively. Patients treated with HFNC, NIV, or IMV within the first 24 h of hospital admission were included in this study. Descriptive statistics, random forest, and logistic regression analyses were used to describe clinical characteristics and compare clinical outcomes among patients treated with the different types of advanced respiratory support. Results: A total of 66,565 patients were included in this study. Overall, 82.6% of patients were treated in HIC, and 40.6% were admitted to the hospital during the first pandemic wave. During the first 24 h after hospital admission, patients in HICs were more frequently treated with HFNC (48.0%), followed by NIV (38.6%) and IMV (13.4%). In contrast, patients admitted in lower- and middle-income countries (LMICs) were less frequently treated with HFNC (16.1%) and the majority received IMV (59.1%). The failure rate of non-invasive respiratory support (i.e. HFNC or NIV) was 15.5%, of which 71.2% were from HIC and 28.8% from LMIC. The variables most strongly associated with non-invasive ventilation failure, defined as progression to IMV, were high leukocyte counts at hospital admission (OR [95%CI]; 5.86 [4.83-7.10]), treatment in an LMIC (OR [95%CI]; 2.04 [1.97-2.11]), and tachypnoea at hospital admission (OR [95%CI]; 1.16 [1.14-1.18]). Patients who failed HFNC/NIV had a higher 28-day fatality ratio (OR [95%CI]; 1.27 [1.25-1.30]). Conclusions: In the present international cohort, the most frequently used advanced respiratory support was the HFNC. However, IMV was used more often in LMIC. Higher leucocyte count, tachypnoea, and treatment in LMIC were risk factors for HFNC/NIV failure. HFNC/NIV failure was related to worse clinical outcomes, such as 28-day mortality. Trial registration This is a prospective observational study; therefore, no health care interventions were applied to participants, and trial registration is not applicable