Centrosome reduction in newly-generated tetraploid cancer cells obtained by separase depletion

Altres ajuts: Fundación Científica de la Asociación Española Contra el Cáncer (GCB13131592CAST)Tetraploidy, a common feature in cancer, results in the presence of extra centrosomes, which has been associated with chromosome instability (CIN) and aneuploidy. Deregulation in the number of centrosomes triggers tumorigenesis. However, how supernumerary centrosomes evolve during the emergence of tetraploid cells remains yet to be elucidated. Here, generating tetraploid isogenic clones in colorectal cancer and in non-transformed cells, we show that near-tetraploid clones exhibit a significant increase in the number of centrosomes. Moreover, we find that centrosome area in near-tetraploids is twice as large as in near-diploids. To evaluate whether centrosome clustering was occurring, we next analysed the number of centrioles revealing centriole amplification. Notwithstanding, more than half of the near-tetraploids maintained in culture do not present centrosome aberrations. To test whether cells progressively lost centrioles after becoming near-tetraploid, we transiently transfected diploid cells with siRNA against ESPL1 /Separase, a protease responsible for triggering anaphase, to generate newly near-tetraploid cells. Finally, using this model, we assessed the number of centrioles at different time-points after tetraploidization finding that near-tetraploids rapidly lose centrosomes over time. Taken together, these data demonstrate that although most cells reduce supernumerary centrosomes after tetraploidization, a small fraction retains extra centrioles, potentially resulting in CIN

Chemical composition and antioxidant activity of phenolic extracts from peanut skins obtained by different industrial process

Peanut skins present phenolic compounds with antioxidant properties which are excellent as a source of natural antioxidants. In food products, the antioxidants have the function ofneutralizedthe action of free radicals produced by oxidation reactions. The objective of this study was to determine the chemical composition and antioxidant activity of extracts rich in phenolic compounds form peanut skins obtained by two industrial process.Fil: Larrauri, Mariana. Universidad Nacional de Córdoba. Facultad de Ciencias Agropecuarias; Argentina.Fil: Larrauri, Mariana. Consejo Nacional de Investigaciones Científicas y Técnicas. Instituto Multidisciplinario de Biología Vegetal; Argentina.Fil: Asensio, Claudia M. Universidad Nacional de Córdoba. Facultad de Ciencias Agropecuarias; Argentina.Fil: Asensio, Claudia M. Consejo Nacional de Investigaciones Científicas y Técnicas. Instituto Multidisciplinario de Biología Vegetal; Argentina.Fil: Martín, María Paula. Universidad Nacional de Córdoba. Facultad de Ciencias Agropecuarias; Argentina.Fil: Martín, María Paula. Consejo Nacional de Investigaciones Científicas y Técnicas. Instituto Multidisciplinario de Biología Vegetal; Argentina.Fil: Zunino, M. Paula. Universidad Nacional de Córdoba. Facultad de Ciencias Exactas, Físicas y Naturales. Instituto de Ciencia y Tecnología de los Alimentos; Argentina.Fil: Zunino, M. Paula. Consejo Nacional de Investigaciones Científicas y Técnicas. Instituto Multidisciplinario de Biología Vegetal; Argentina.Fil: Zygadlo, Julio A. Universidad Nacional de Córdoba. Facultad de Ciencias Exactas, Físicas y Naturales. Instituto de Ciencia y Tecnología de los Alimentos; Argentina.Fil: Zygadlo, Julio A. Consejo Nacional de Investigaciones Científicas y Técnicas. Instituto Multidisciplinario de Biología Vegetal; Argentina.Fil: Grosso, Nelson R. Universidad Nacional de Córdoba. Facultad de Ciencias Agropecuarias; Argentina.Fil: Grosso, Nelson R. Consejo Nacional de Investigaciones Científicas y Técnicas. Instituto Multidisciplinario de Biología Vegetal; Argentina.Fil: Nepote, Valeria. Universidad Nacional de Córdoba. Facultad de Ciencias Exactas, Físicas y Naturales. Instituto de Ciencia y Tecnología de los Alimentos; Argentina.Fil: Nepote, Valeria. Consejo Nacional de Investigaciones Científicas y Técnicas. Instituto Multidisciplinario de Biología Vegetal; Argentina.Otras Ciencias Agrícola

Antioxidant activity of monoterpenes and synergist antioxidant effect with BHT

Fil: Quiroga, Patricia R. Universidad Nacional de Córdoba. Facultad de Ciencias Agropecuarias; Argentina.Fil: Quiroga, Patricia R. Universidad Nacional de Córdoba. Consejo Nacional de Investigaciones Científicas y Técnicas. Instituto Multidisciplinario de Biología Vegetal; Argentina.Fil: Asensio, Claudia M. Universidad Nacional de Córdoba. Facultad de Ciencias Agropecuarias; Argentina.Fil: Asensio, Claudia M. Universidad Nacional de Córdoba. Consejo Nacional de Investigaciones Científicas y Técnicas. Instituto Multidisciplinario de Biología Vegetal; Argentina.Fil: Larrauri, Mariana. Universidad Nacional de Córdoba. Facultad de Ciencias Agropecuarias; Argentina.Fil: Larrauri, Mariana. Universidad Nacional de Córdoba. Consejo Nacional de Investigaciones Científicas y Técnicas. Instituto Multidisciplinario de Biología Vegetal; Argentina.Fil: Martin, María P. Universidad Nacional de Córdoba. Facultad de Ciencias Agropecuarias; Argentina.Fil: Martin, María P. Universidad Nacional de Córdoba. Consejo Nacional de Investigaciones Científicas y Técnicas. Instituto Multidisciplinario de Biología Vegetal; Argentina.Fil: Rivero, Cecilia G. Universidad Nacional de Córdoba. Facultad de Ciencias Agropecuarias; Argentina.Fil: Rivero, Cecilia G. Universidad Nacional de Córdoba. Consejo Nacional de Investigaciones Científicas y Técnicas. Instituto Multidisciplinario de Biología Vegetal; Argentina.Fil: Grosso, Nelson R. Universidad Nacional de Córdoba. Facultad de Ciencias Agropecuarias; Argentina.Fil: Grosso, Nelson R. Universidad Nacional de Córdoba. Consejo Nacional de Investigaciones Científicas y Técnicas. Instituto Multidisciplinario de Biología Vegetal; Argentina.Fil: Nepote, V. Universidad Nacional de Córdoba. Facultad de Ciencias Agropecuarias; Argentina.Fil: Nepote, V. Universidad Nacional de Córdoba. Consejo Nacional de Investigaciones Científicas y Técnicas. Instituto Multidisciplinario de Biología Vegetal; Argentina.Synthetic antioxidants are used in many foods. Their health safety is questioned. Monoterpenesobtained from essential oils have shown antioxidant activity. The objective of this study was to evaluate the preserving effect of monoterpenes: thymol, carvacrol, and sabineno hydrate acting as antioxidant additives.Fil: Quiroga, Patricia R. Universidad Nacional de Córdoba. Facultad de Ciencias Agropecuarias; Argentina.Fil: Quiroga, Patricia R. Universidad Nacional de Córdoba. Consejo Nacional de Investigaciones Científicas y Técnicas. Instituto Multidisciplinario de Biología Vegetal; Argentina.Fil: Asensio, Claudia M. Universidad Nacional de Córdoba. Facultad de Ciencias Agropecuarias; Argentina.Fil: Asensio, Claudia M. Universidad Nacional de Córdoba. Consejo Nacional de Investigaciones Científicas y Técnicas. Instituto Multidisciplinario de Biología Vegetal; Argentina.Fil: Larrauri, Mariana. Universidad Nacional de Córdoba. Facultad de Ciencias Agropecuarias; Argentina.Fil: Larrauri, Mariana. Universidad Nacional de Córdoba. Consejo Nacional de Investigaciones Científicas y Técnicas. Instituto Multidisciplinario de Biología Vegetal; Argentina.Fil: Martin, María P. Universidad Nacional de Córdoba. Facultad de Ciencias Agropecuarias; Argentina.Fil: Martin, María P. Universidad Nacional de Córdoba. Consejo Nacional de Investigaciones Científicas y Técnicas. Instituto Multidisciplinario de Biología Vegetal; Argentina.Fil: Rivero, Cecilia G. Universidad Nacional de Córdoba. Facultad de Ciencias Agropecuarias; Argentina.Fil: Rivero, Cecilia G. Universidad Nacional de Córdoba. Consejo Nacional de Investigaciones Científicas y Técnicas. Instituto Multidisciplinario de Biología Vegetal; Argentina.Fil: Grosso, Nelson R. Universidad Nacional de Córdoba. Facultad de Ciencias Agropecuarias; Argentina.Fil: Grosso, Nelson R. Universidad Nacional de Córdoba. Consejo Nacional de Investigaciones Científicas y Técnicas. Instituto Multidisciplinario de Biología Vegetal; Argentina.Fil: Nepote, V. Universidad Nacional de Córdoba. Facultad de Ciencias Agropecuarias; Argentina.Fil: Nepote, V. Universidad Nacional de Córdoba. Consejo Nacional de Investigaciones Científicas y Técnicas. Instituto Multidisciplinario de Biología Vegetal; Argentina.Alimentos y Bebida

Proctitis in patients with monkeypox infection: a single‑center analysis of 42 consecutive cases from a multidisciplinary observational study on monkeypox proctitis

Background: The current monkeypox (MP) virus outbreak was declared an international emergency in July 2022. The aim of this report is to describe our initial experience with patients with MP, focusing on proctitis. Methods: We conducted an observational study between 20 May and 31 July 2022, on patients with MP at a reference tertiary center in Madrid, Spain. A descriptive analysis on MP was performed, focusing on its characteristics, symptoms, diagnosis, and outcomes. Results: A total of 143 positive MP cases were diagnosed in our center; 42 of them [all male, median age 39 years (range: 22–57 years)] had proctitis (29.37%), and 3 patients (2.09%/MP total cases and 7.14%/MP proctitis) required surgical drainage of a perianal abscess. Conclusions: General and digestive surgeons must be aware of the presence of proctological impairment and complications due to MP viru

Virulence Regulator EspR of Mycobacterium tuberculosis Is a Nucleoid-Associated Protein

The principal virulence determinant of Mycobacterium tuberculosis (Mtb), the ESX-1 protein secretion system, is positively controlled at the transcriptional level by EspR. Depletion of EspR reportedly affects a small number of genes, both positively or negatively, including a key ESX-1 component, the espACD operon. EspR is also thought to be an ESX-1 substrate. Using EspR-specific antibodies in ChIP-Seq experiments (chromatin immunoprecipitation followed by ultra-high throughput DNA sequencing) we show that EspR binds to at least 165 loci on the Mtb genome. Included in the EspR regulon are genes encoding not only EspA, but also EspR itself, the ESX-2 and ESX-5 systems, a host of diverse cell wall functions, such as production of the complex lipid PDIM (phenolthiocerol dimycocerosate) and the PE/PPE cell-surface proteins. EspR binding sites are not restricted to promoter regions and can be clustered. This suggests that rather than functioning as a classical regulatory protein EspR acts globally as a nucleoid-associated protein capable of long-range interactions consistent with a recently established structural model. EspR expression was shown to be growth phase-dependent, peaking in the stationary phase. Overexpression in Mtb strain H37Rv revealed that EspR influences target gene expression both positively or negatively leading to growth arrest. At no stage was EspR secreted into the culture filtrate. Thus, rather than serving as a specific activator of a virulence locus, EspR is a novel nucleoid-associated protein, with both architectural and regulatory roles, that impacts cell wall functions and pathogenesis through multiple genes

New factors for protein transport identified by a genome-wide CRISPRi screen in mammalian cells

Protein and membrane trafficking pathways are critical for cell and tissue homeostasis. Traditional genetic and biochemical approaches have shed light on basic principles underlying these processes. However, the list of factors required for secretory pathway function remains incomplete, and mechanisms involved in their adaptation poorly understood. Here, we present a powerful strategy based on a pooled genome-wide CRISPRi screen that allowed the identification of new factors involved in protein transport. Two newly identified factors, TTC17 and CCDC157, localized along the secretory pathway and were found to interact with resident proteins of ER-Golgi membranes. In addition, we uncovered that upon TTC17 knockdown, the polarized organization of Golgi cisternae was altered, creating glycosylation defects, and that CCDC157 is an important factor for the fusion of transport carriers to Golgi membranes. In conclusion, our work identified and characterized new actors in the mechanisms of protein transport and secretion, and opens stimulating perspectives for the use of our platform in physiological and pathological contexts.Includes Wellcome Trust, MRC and H202

Role of age and comorbidities in mortality of patients with infective endocarditis

[Purpose]: The aim of this study was to analyse the characteristics of patients with IE in three groups of age and to assess the ability of age and the Charlson Comorbidity Index (CCI) to predict mortality. [Methods]: Prospective cohort study of all patients with IE included in the GAMES Spanish database between 2008 and 2015.Patients were stratified into three age groups:<65 years,65 to 80 years,and ≥ 80 years.The area under the receiver-operating characteristic (AUROC) curve was calculated to quantify the diagnostic accuracy of the CCI to predict mortality risk. [Results]: A total of 3120 patients with IE (1327 < 65 years;1291 65-80 years;502 ≥ 80 years) were enrolled.Fever and heart failure were the most common presentations of IE, with no differences among age groups.Patients ≥80 years who underwent surgery were significantly lower compared with other age groups (14.3%,65 years; 20.5%,65-79 years; 31.3%,≥80 years). In-hospital mortality was lower in the <65-year group (20.3%,<65 years;30.1%,65-79 years;34.7%,≥80 years;p < 0.001) as well as 1-year mortality (3.2%, <65 years; 5.5%, 65-80 years;7.6%,≥80 years; p = 0.003).Independent predictors of mortality were age ≥ 80 years (hazard ratio [HR]:2.78;95% confidence interval [CI]:2.32–3.34), CCI ≥ 3 (HR:1.62; 95% CI:1.39–1.88),and non-performed surgery (HR:1.64;95% CI:11.16–1.58).When the three age groups were compared,the AUROC curve for CCI was significantly larger for patients aged <65 years(p < 0.001) for both in-hospital and 1-year mortality. [Conclusion]: There were no differences in the clinical presentation of IE between the groups. Age ≥ 80 years, high comorbidity (measured by CCI),and non-performance of surgery were independent predictors of mortality in patients with IE.CCI could help to identify those patients with IE and surgical indication who present a lower risk of in-hospital and 1-year mortality after surgery, especially in the <65-year group

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