Characterization of the Small RNA Transcriptome of the Marine Coccolithophorid, Emiliania huxleyi

Small RNAs (smRNAs) control a variety of cellular processes by silencing target genes at the transcriptional or post-transcription level. While extensively studied in plants, relatively little is known about smRNAs and their targets in marine phytoplankton, such as Emiliania huxleyi (E. huxleyi). Deep sequencing was performed of smRNAs extracted at different time points as E. huxleyi cells transition from logarithmic to stationary phase growth in batch culture. Computational analyses predicted 18 E. huxleyi specific miRNAs. The 18 miRNA candidates and their precursors vary in length (18-24 nt and 71-252 nt, respectively), genome copy number (3-1,459), and the number of genes targeted (2-107). Stem-loop real time reverse transcriptase (RT) PCR was used to validate miRNA expression which varied by nearly three orders of magnitude when growth slows and cells enter stationary phase. Stem-loop RT PCR was also used to examine the expression profiles of miRNA in calcifying and non-calcifying cultures, and a small subset was found to be differentially expressed when nutrients become limiting and calcification is enhanced. In addition to miRNAs, endogenous small RNAs such as ra-siRNAs, ta-siRNAs, nat-siRNAs, and piwiRNAs were predicted along with the machinery for the biogenesis and processing of si-RNAs. This study is the first genome-wide investigation smRNAs pathways in E. huxleyi. Results provide new insights into the importance of smRNAs in regulating aspects of physiological growth and adaptation in marine phytoplankton and further challenge the notion that smRNAs evolved with multicellularity, expanding our perspective of these ancient regulatory pathways

Nivel de vocabulario receptivo en niños de 4 y 5 años de centros educativos estatales y privados del distrito de Surquillo

La presente investigación se llevó a cabo con el objetivo de comparar el nivel de vocabulario receptivo entre niños de ambos sexos de 4 y 5 años de centros educativos estatales y privados del distrito de Surquillo. El método utilizado fue el descriptivo, la muestra estuvo conformada por 115 niños y niñas de instituciones educativas estatales y 110 niños de ambos sexos de instituciones educativas privadas, a quienes se les aplicó el Test de Vocabulario en Imágenes Peabody PPVT - III. Los hallazgos encontrados arrojan que existen diferencias significativas en el vocabulario receptivo en función a la edad, género y tipo de gestión educativa, encontrándose mejores niveles en los alumnos de las instituciones educativas privadas. También se encontró que no existen diferencias entre las niñas mujeres de 4 años de ambas gestiones educativas.This research was conducted in order to compare the level of receptive vocabulary in children of both sexes aged 4 and 5 years of state and private schools in the district Surquillo. The method used was descriptive, the sample consisted of 115 children in state schools and 110 children of both sexes in private schools, who were administered the Test Peabody Picture Vocabulary PPVT - III. The findings shed significant differences in receptive vocabulary according to age, gender and type of education management, higher levels being found in students of private educational institutions. We also found no difference between women girls 4 years of both educational management.Tesi

FINANCIAMIENTO Y LIQUIDEZ EN LAS MYPES TEXTIL GAMARRA- LA VICTORIA 2016

La presente investigación sobre el Financiamiento y liquidez en las Mypes textil gamarra- la victoria 2016, tuvo como objetivo general determinar que existe relación entre Financiamiento y Liquidez en las Mypes textil Gamarra - La Victoria 2016. Según Rodés (2014), El financiamiento es la forma como conseguir los recursos necesarios para emprender un proyecto, que incluye un coste determinado o para llevar a cabo sus actividades económicas y su crecimiento empresarial. Según Flores (2011) La liquidez es la capacidad de pago que tiene una empresa, para hacer frente sus obligaciones conforme estas vayan venciendo su plazo. El diseño de la investigación es no experimental de corte transversal, tipo de estudio básico, nivel de investigación descriptiva correlacional ya que las dos variables están relacionadas entre sí y su enfoque cuantitativo. La población de la investigación es 4,993 Mypes y la muestra está conformada por 50 Mypes del sector textil en la galería Guizado que se encuentra ubicado en el emporio de Gamarra, la técnica empleada para la recolección de datos es la encuesta y como instrumento se utilizó el cuestionario medido a través de la escala de Likert, las cuales fueron validados por 6 expertos profesionales, para el procesamiento de los datos se realizó con la estadística del software SPSS Statistics 22. Se llegó a la conclusión, que existe una correlación significativa de 0.744 entre el financiamiento y la liquidez en las Mypes, gracias a los resultados de la prueba de hipótesis

Development of a mouse model for spontaneous oral squamous cell carcinoma in Fanconi anemia

Head and neck squamous cell carcinoma; Mouse model; Oral mucosaCarcinoma de células escamosas de cabeza y cuello; Modelo de ratón; Mucosa oralCarcinoma de cèl·lules escamoses de cap i coll; Model de ratolí; Mucosa oralFanconi anemia (FA) patients frequently develop oral squamous cell carcinoma (OSCC). This cancer in FA patients is diagnosed within the first 3–4 decades of life, very often preceded by lesions that suffer a malignant transformation. In addition, they respond poorly to current treatments due to toxicity or multiple recurrences. Translational research on new chemopreventive agents and therapeutic strategies has been unsuccessful partly due to scarcity of disease models or failure to fully reproduce the disease. Here we report that Fanca gene knockout mice (Fanca-/-) frequently display pre-malignant lesions in the oral cavity. Moreover, when these animals were crossed with animals having conditional deletion of Trp53 gene in oral mucosa (K14cre;Trp53F2-10/F2-10), they spontaneously developed OSCC with high penetrance and a median latency of less than ten months. Tumors were well differentiated and expressed markers of squamous differentiation, such as keratins K5 and K10. In conclusion, Fanca and Trp53 genes cooperate to suppress oral cancer in mice, and Fanca-/-;K14cre;Trp53F2-10/F2-10 mice constitute the first animal model of spontaneous OSCC in FA.This study has been funded by Instituto de Salud Carlos III (ISCIII) through the projects CB16/12/00228/CIBERONC, PI18/00263 and P121/00208 and co-funded by FEDER and the European Union; and grants from the Spanish Fundacion Anemia de Fanconi and Fanconi Anemia Research Fund USA. J.P. was supported by a FEDER co-funded grant (ref PEJ2018-002040-A) from the Ministerio de Ciencia, Innovación y Universidades. J.O. was supported by a FEDER co-funded grant (ref PEJ-2019-TL_BMD-12905) from the Comunidad de Madrid. The funding sources were not involved in study design; in the collection, analysis and interpretation of data; in the writing of the report; and in the decision to submit the article for publication

Early Diagnosis of Oral Cancer and Lesions in Fanconi Anemia Patients: A Prospective and Longitudinal Study Using Saliva and Plasma

Fanconi anemia; Cancer gene; SalivaAnèmia de Fanconi; Gen del càncer; SalivaAnemia de Fanconi; Gen del cáncer; SalivaFanconi anemia (FA) patients display an exacerbated risk of oral squamous cell carcinoma (OSCC) and oral potentially malignant lesions (OPMLs) at early ages. As patients have defects in their DNA repair mechanisms, standard-of-care treatments for OSCC such as radiotherapy and chemotherapy, give rise to severe toxicities. New methods for early diagnosis are urgently needed to allow for treatment in early disease stages and achieve better clinical outcomes. We conducted a prospective, longitudinal study wherein liquid biopsies from sixteen patients with no clinical diagnoses of OPML and/or OSCC were analyzed for the presence of mutations in cancer genes. The DNA from saliva and plasma were sequentially collected and deep-sequenced, and the clinical evaluation followed over a median time of approximately 2 years. In 9/16 FA patients, we detected mutations in cancer genes (mainly TP53) with minor allele frequencies (MAF) of down to 0.07%. Importantly, all patients that had mutations and clinical follow-up data after mutation detection (n = 6) developed oral precursor lesions or OSCC. The lead-time between mutation detection and tumor diagnosis ranged from 23 to 630 days. Strikingly, FA patients without mutations displayed a significantly lower risk of developing precursor lesions or OSCCs. Therefore, our diagnostic approach could help to stratify FA patients into risk groups, which would allow for closer surveillance for OSCCs or precursor lesions.This study was funded by Instituto de Salud Carlos III (ISCIII) through the projects CB16/12/00228/CIBERONC, PI18/00263 and P121/00208; co-funded by FEDER and the European Union; and funded by a grant from the Spanish Fundacion Anemia de Fanconi. J.P. was supported by a FEDER co-funded grant (ref. PEJ2018-002040-A) from the Ministerio de Ciencia e Innovación. J.O. was supported by a FEDER co-funded grant (ref. PEJ-2019-TL_BMD-12905) from the Comunidad de Madrid. The funding sources were not involved in study design; in the collection, analysis and interpretation of data; in the writing of the report; or in the decision to submit the article for publication

Clinical behavior and outcomes of breast cancer in young women with germline BRCA pathogenic variants

Càncer de mama; Genètica del càncerCáncer de mama; Genética del cáncerBreast cancer; Cancer geneticsYoung breast cancer (BC) patients carrying a germline BRCA pathogenic variant (mBRCA) have similar outcomes as non-carriers. However, the impact of the type of gene (BRCA1 vs. BRCA2) and hormone receptor status (positive [HR+] vs. negative [HR−]) on clinical behavior and outcomes of mBRCA BC remains largely unknown. This is an international, multicenter, hospital-based, retrospective cohort study that included mBRCA patients diagnosed, between January 2000 and December 2012, with stage I–III invasive early BC at age ≤40 years. From 30 centers worldwide, 1236 young mBRCA BC patients were included. Among 808 and 428 patients with mBRCA1 or mBRCA2, 191 (23.6%) and 356 (83.2%) had HR+tumors, respectively (P < 0.001). Median follow-up was 7.9 years. Second primary BC (P = 0.009) and non-BC malignancies (P = 0.02) were more frequent among mBRCA1 patients while distant recurrences were less frequent (P = 0.02). Irrespective of hormone receptor status, mBRCA1 patients had worse disease-free survival (DFS; adjusted HR = 0.76, 95% CI = 0.60–0.96), with no difference in distant recurrence-free interval (DRFI) and overall survival (OS). Patients with HR+ disease had more frequent distant recurrences (P < 0.001) and less frequent second primary malignancies (BC: P = 0.005; non-BC: P = 0.18). No differences in DFS and OS were observed according to hormone receptor status, with a tendency for worse DRFI (adjusted HR = 1.39, 95% CI = 0.94–2.05) in patients with HR+ BC. Type of mBRCA gene and hormone receptor status strongly impact BC clinical behavior and outcomes in mBRCA young patients. These results provide important information for patients’ counseling on treatment, prevention, and surveillance strategies.This study received partial financial support by grants from the Italian Ministry of Health - 5 × 1000 funds 2017 (no grant number), the Italian Association for Cancer Research (AIRC; MFAG 2020 ID 24698), and “Les Amis de l’Institut Bordet” foundation (no grant number). The funders had no role in the design and conduct of the study; collection, management, analysis, and interpretation of the data; preparation, review, or approval of the manuscript; and decision to submit the manuscript for publication. M.L. acknowledges the support from the European Society for Medical Oncology (ESMO) for a Translational Research Fellowship at the Institut Jules Bordet in Brussels (Belgium) at the time of study conduction. K.P. acknowledges the support from a predoctoral clinical ‘KOOR’ mandate from the University Hospitals Leuven (Leuven, Belgium). F.P.D. acknowledges the support for a postdoctoral clinical mandate (2017-034) from the not-for-profit organization ‘Foundation Against Cancer’ (Brussels, Belgium). A.H.P. acknowledges the support from Susan G. Komen and Breast Cancer Research Foundation (BCRF). J.H. acknowledges the support from the Carlos III National Health Institute funded by FEDER funds—a way to build Europe (PI16/11363). This research was presented in the Poster Spotlight session at the 2020 San Antonio Breast Cancer Symposium (SABCS), San Antonio, TX, United States of America, on 8–12 December 2020

Safety of assisted reproductive techniques in young women harboring germline pathogenic variants in BRCA1/2 with a pregnancy after prior history of breast cancer

Breast cancer fertility; Pregnancy; SurvivalFertilidad y cáncer de mama; Embarazo; SupervivenciaFertilitat i càncer de mama; Embaràs; SupervivènciaBackground Knowledge is growing on the safety of assisted reproductive techniques (ART) in cancer survivors. No data exist, however, for the specific population of breast cancer patients harboring germline BRCA1/2 pathogenic variants. Patients and methods This is a multicenter retrospective cohort study across 30 centers worldwide including women diagnosed at ≤40 years with stage I-III breast cancer, between January 2000 and December 2012, harboring known germline BRCA1/2 pathogenic variants. Patients included in this analysis had a post-treatment pregnancy either achieved through use of ART (ART group) or naturally (non-ART group). ART procedures included ovulation induction, ovarian stimulation for in vitro fertilization or intracytoplasmic sperm injection, and embryo transfer under hormonal replacement therapy. Results Among the 1424 patients registered in the study, 168 were eligible for inclusion in the present analysis, of whom 22 were in the ART group and 146 in the non-ART group. Survivors in the ART group conceived at an older age compared with those in the non-ART group (median age: 39.7 versus 35.4 years, respectively). Women in the ART group experienced more delivery complications compared with those in the non-ART group (22.1% versus 4.1%, respectively). No other apparent differences in obstetrical outcomes were observed between cohorts. The median follow-up from pregnancy was 3.4 years (range: 0.8-8.6 years) in the ART group and 5.0 years (range: 0.8-17.6 years) in the non-ART group. Two patients (9.1%) in the ART group experienced a disease-free survival event (specifically, a locoregional recurrence) compared with 40 patients (27.4%) in the non-ART group. In the ART group, no patients deceased compared with 10 patients (6.9%) in the non-ART group. Conclusion This study provides encouraging safety data on the use of ART in breast cancer survivors harboring germline pathogenic variants in BRCA1/2, when natural conception fails or when they opt for ART in order to carry out preimplantation genetic testing.The present work was supported by the Italian Association for Cancer Research (‘Associazione Italiana per la Ricerca sul Cancro’, AIRC; MFAG 2020 ID 24698) and the Italian Ministry of Health (5 × 1000 funds 2017). MC and ID acknowledge the Fonds National de la Recherche Scientifique (FNRS and Télévie 7.6508.20) and Fonds Erasme for their financial support

Exercise alters liver mitochondria phospholipidomic profile and mitochondrial activity in non-alcoholic steatohepatitis

Mitochondrial membrane lipid composition is a critical factor in non-alcoholic steatohepatitis (NASH). Exercise is the most prescribed therapeutic strategy against NASH and a potential modulator of lipidmembrane. Thus, we aimed to analyze whether physical exercise exerted preventive (voluntary physical activity - VPA) and therapeutic (endurance training - ET) effect on NASH-induced mitochondrial membrane changes. Sprague-Dawley rats (n = 36) were divided into standard-diet sedentary (SS, n = 12),standard-diet VPA (SVPA, n = 6), high-fat diet sedentary (HS, n = 12) and high-fat diet VPA (HVPA, n = 6). After 9 weeks of diet-specific feeding, half of SS and HS group were engaged in an ET program for 8 weeks/5 day/week/1 h/day (SET, HET). Liver mitochondria were isolated for oxygen consumption and transmembrane-electric potential (Δψ) assays. Mitochondrial phospholipid classes and fatty acids were quantified through thin layer chromatography and gas chromatography, respectively, while cardiolipin(CL), phosphatidylcholine (PC) phosphatidylethanolamine (PE) and phosphatidylinositol (PI) molecular profile was determined by electrospray mass spectrometry. In parallel with histological signs of NASH,high-fat diet decreased PI, CL and PC/PE ratio, whereas PE and phosphatidic acid content increased insedentary animals (HS vs. SS). Moreover, a decrease in linolelaidic, monounsaturated fatty acids content and an increase in saturated fatty acids (SFAS) were observed. Along with phospholipidomic alterations,HS animals showed a decrease in respiratory control ratio (RCR), Δψ and FCCP-induced uncoupling respiration (HS vs. SS). Both phospholipidomic (PC/PE, SFAS) and mitochondrial respiratory alterations were counteracted by exercise interventions. Exercise used as preventive (VPA) or therapeutic (ET) strategies preserved liver mitochondrial phospholipidomic profile and maintained mitochondrial function in a model of NASH

Clinical consequences of BRCA2 hypomorphism

Breast cancer; Cancer geneticsCáncer de mama; Genética del cáncerCàncer de mama; Genètica del càncerThe tumor suppressor FANCD1/BRCA2 is crucial for DNA homologous recombination repair (HRR). BRCA2 biallelic pathogenic variants result in a severe form of Fanconi anemia (FA) syndrome, whereas monoallelic pathogenic variants cause mainly hereditary breast and ovarian cancer predisposition. For decades, the co-occurrence in trans with a clearly pathogenic variant led to assume that the other allele was benign. However, here we show a patient with biallelic BRCA2 (c.1813dup and c.7796 A > G) diagnosed at age 33 with FA after a hypertoxic reaction to chemotherapy during breast cancer treatment. After DNA damage, patient cells displayed intermediate chromosome fragility, reduced survival, cell cycle defects, and significantly decreased RAD51 foci formation. With a newly developed cell-based flow cytometric assay, we measured single BRCA2 allele contributions to HRR, and found that expression of the missense allele in a BRCA2 KO cellular background partially recovered HRR activity. Our data suggest that a hypomorphic BRCA2 allele retaining 37–54% of normal HRR function can prevent FA clinical phenotype, but not the early onset of breast cancer and severe hypersensitivity to chemotherapy

Evaluación de aislamientos de Trichoderma spp. contra el patógeno Colletotrichum theobromicola causante de la antracnosis del olivo

PosterLa antracnosis del olivo causada por Colletotrichum spp es una de las principales enfermedades del olivo la cual genera pérdidas elevadas debido a la pudrición del fruto y la reducción en la calidad del aceite C theobromicola es una de las especies más frecuente en fruto a cosecha Trichoderma spp es el antagonista más utilizado para el control de enfermedades de plantas producidas por hongos Los mecanismos descriptos por los cuales Trichoderma desplaza al fitopatógeno son a) competición directa por el espacio o por los nutrientes, b) producción de metabolitos antibióticos, c) parasitismo directo sobre los hongos fitopatógenos y d) inducción de resistencia sistémica El objetivo de este trabajo fue evaluar la capacidad antagónica de 15 aislamientos de Trichoderma pertenecientes a la colección IPAVE, frente al patógeno C theobromicola IPAVE 072 en ensayos in vitro.Instituto de Patología VegetalFil: Valetti, Lucio. Instituto Nacional de Tecnología Agropecuaria (INTA). Instituto de Patología Vegetal; ArgentinaFil: Valetti, Lucio. Consejo Nacional de Investigaciones Científicas y Técnicas. Unidad de Fitopatología y Modelización Agrícola (UFyMA); ArgentinaFil: Bernardi Lima, Nelson. Consejo Nacional de Investigaciones Científicas y Técnicas. Unidad de Fitopatología y Modelización Agrícola (UFyMA); ArgentinaFil: Bernardi Lima, Nelson. Instituto Nacional de Tecnología Agropecuaria (INTA). Instituto de Patología Vegetal; ArgentinaFil: Pastor, Silvina Estela. Instituto Nacional de Tecnología Agropecuaria (INTA). Instituto de Patología Vegetal; ArgentinaFil: Pastor, Silvina Estela. Consejo Nacional de Investigaciones Científicas y Técnicas. Unidad de Fitopatología y Modelización Agrícola (UFyMA); ArgentinaFil: Otero, Maria Laura. Instituto Nacional de Tecnología Agropecuaria (INTA). Instituto de Patología Vegetal; ArgentinaFil: Cáceres, Ruth. Universidad Nacional de La Rioja; ArgentinaFil: Quintero, Sara. Universidad Nacional de La Rioja; ArgentinaFil: Maza, Claudia Elizabeth. Instituto Nacional de Tecnología Agropecuaria (INTA). Estación Experimental Agropecuaria Chilecito; ArgentinaFil: Roca, Mónica. Universidad Nacional de La Rioja; ArgentinaFil: Carrasco, Franca Denise. Instituto Nacional de Tecnología Agropecuaria (INTA). Estación Experimental Agropecuaria Catamarca; Argentin