14 research outputs found

    Nucleus-cytoskeleton communication impacts on OCT4-chromatin interactions in embryonic stem cells

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    Background: The cytoskeleton is a key component of the system responsible for transmitting mechanical cues from the cellular environment to the nucleus, where they trigger downstream responses. This communication is particularly relevant in embryonic stem (ES) cells since forces can regulate cell fate and guide developmental processes. However, little is known regarding cytoskeleton organization in ES cells, and thus, relevant aspects of nuclear-cytoskeletal interactions remain elusive. Results: We explored the three-dimensional distribution of the cytoskeleton in live ES cells and show that these filaments affect the shape of the nucleus. Next, we evaluated if cytoskeletal components indirectly modulate the binding of the pluripotency transcription factor OCT4 to chromatin targets. We show that actin depolymerization triggers OCT4 binding to chromatin sites whereas vimentin disruption produces the opposite effect. In contrast to actin, vimentin contributes to the preservation of OCT4-chromatin interactions and, consequently, may have a pro-stemness role. Conclusions: Our results suggest roles of components of the cytoskeleton in shaping the nucleus of ES cells, influencing the interactions of the transcription factor OCT4 with the chromatin and potentially affecting pluripotency and cell fate.Fil: Romero, Juan José. Consejo Nacional de Investigaciones Científicas y Técnicas. Oficina de Coordinación Administrativa Ciudad Universitaria. Instituto de Química Biológica de la Facultad de Ciencias Exactas y Naturales. Universidad de Buenos Aires. Facultad de Ciencias Exactas y Naturales. Instituto de Química Biológica de la Facultad de Ciencias Exactas y Naturales; Argentina. YPF - Tecnología; ArgentinaFil: de Rossi, María Cecilia. Consejo Nacional de Investigaciones Científicas y Técnicas. Oficina de Coordinación Administrativa Ciudad Universitaria. Instituto de Química Biológica de la Facultad de Ciencias Exactas y Naturales. Universidad de Buenos Aires. Facultad de Ciencias Exactas y Naturales. Instituto de Química Biológica de la Facultad de Ciencias Exactas y Naturales; ArgentinaFil: Oses Oliveto, Camila Maite. Consejo Nacional de Investigaciones Científicas y Técnicas. Oficina de Coordinación Administrativa Ciudad Universitaria. Instituto de Química Biológica de la Facultad de Ciencias Exactas y Naturales. Universidad de Buenos Aires. Facultad de Ciencias Exactas y Naturales. Instituto de Química Biológica de la Facultad de Ciencias Exactas y Naturales; ArgentinaFil: Vazquez Echegaray, Camila. Consejo Nacional de Investigaciones Científicas y Técnicas. Oficina de Coordinación Administrativa Ciudad Universitaria. Instituto de Química Biológica de la Facultad de Ciencias Exactas y Naturales. Universidad de Buenos Aires. Facultad de Ciencias Exactas y Naturales. Instituto de Química Biológica de la Facultad de Ciencias Exactas y Naturales; ArgentinaFil: Verneri, Paula. Consejo Nacional de Investigaciones Científicas y Técnicas. Oficina de Coordinación Administrativa Ciudad Universitaria. Instituto de Química Biológica de la Facultad de Ciencias Exactas y Naturales. Universidad de Buenos Aires. Facultad de Ciencias Exactas y Naturales. Instituto de Química Biológica de la Facultad de Ciencias Exactas y Naturales; ArgentinaFil: Francia, Marcos Gabriel. Consejo Nacional de Investigaciones Científicas y Técnicas. Oficina de Coordinación Administrativa Ciudad Universitaria. Instituto de Química Biológica de la Facultad de Ciencias Exactas y Naturales. Universidad de Buenos Aires. Facultad de Ciencias Exactas y Naturales. Instituto de Química Biológica de la Facultad de Ciencias Exactas y Naturales; ArgentinaFil: Guberman, Alejandra Sonia. Consejo Nacional de Investigaciones Científicas y Técnicas. Oficina de Coordinación Administrativa Ciudad Universitaria. Instituto de Química Biológica de la Facultad de Ciencias Exactas y Naturales. Universidad de Buenos Aires. Facultad de Ciencias Exactas y Naturales. Instituto de Química Biológica de la Facultad de Ciencias Exactas y Naturales; Argentina. Universidad de Buenos Aires. Facultad de Ciencias Exactas y Naturales. Departamento de Fisiología, Biología Molecular y Celular; ArgentinaFil: Levi, Valeria. Consejo Nacional de Investigaciones Científicas y Técnicas. Oficina de Coordinación Administrativa Ciudad Universitaria. Instituto de Química Biológica de la Facultad de Ciencias Exactas y Naturales. Universidad de Buenos Aires. Facultad de Ciencias Exactas y Naturales. Instituto de Química Biológica de la Facultad de Ciencias Exactas y Naturales; Argentina. Universidad de Buenos Aires. Facultad de Farmacia y Bioquímica. Departamento de Química Biológica; Argentin

    Molecular aggregation of naphthalimide organic semiconductors assisted by amphiphilic and lipophilic interactions: a joint theoretical and experimental study

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    Amphiphilic and lipophilic donor–acceptor naphthalimide–oligothiophene assemblies exhibiting almost identical intramolecular properties, but differing in their intermolecular interactions, have been synthesized. Here we analyze the effect of replacing the normally used lipophilic alkyl chains with hydrophilic ones in directing molecular aggregation from an antiparallel to a parallel stacking. This different molecular packing of the amphiphilic, NIP-3TAmphi, and lipophilic, NIP-3TLipo, systems is assessed by electronic spectroscopies, scanning electronic microscopy and DFT quantum-chemical calculations. Theoretical calculations indicate that the presence of amphiphilic interactions promotes a face-to-face parallel arrangement of neighbor molecules, which induces improved electronic coupling and therefore enhances the charge transport ability and photoconducting properties of this type of materials. Time of flight and photoconducting measurements are used to determine the impact of the amphiphilic and lipophilic interactions on their possible performance in optoelectronic devices.We thank the MINECO of Spain (MAT2014-52305-P and MAT2016-77608-C3-2-P) and the UCM-BSCH joint project (GR3/14-910759), for financial support at Complutense University of Madrid. Research at University of Malaga was supported by MINECO (CTQ2015-66897-P) and Junta de Andalucia (P09-4708). R. P. O. and I. A.-M. thank the MINECO of Spain for a “Ramón y Cajal” research contract and for a predoctoral fellowship, respectively. The work performed at the University of Alicante was funded by MINECO through grant no. MAT-2011-28167-C02-01

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

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    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

    Effective interplay of donor and acceptor groups for tuning optoelectronic properties in oligothiophene–naphthalimide assemblies

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    In this work, a series of naphthalimide fused thienopyrazine derivatives was designed, and their synthesis and characterization are reported herein. The interaction of this building block with a donor terthiophene fragment laterally substituted by a series of donor and acceptor constituents was analyzed in depth. This strategy was proven to efficiently modulate both the energy and topology of the frontier molecular orbitals involved in the charge transport mechanism. The interplay between the donor and acceptor strengths of the different units composing the material structure is thus essential to efficiently modulate charge carriers and transport properties and to finely tune the optical and electronic structures of the presented organic semiconductors.This work was financially supported by MINECO (MAT2016-77608-C3-2-P), MICINN (PID2019-106268GB-C33) and the UCM (INV.GR.00.1819.10759). MJAN gratefully acknowledges Universidad Rey Juan Carlos for a predoctoral contract. The university of Málaga acknowledges support from Junta de Andalucia (UMA18-FEDERJA-080) and MICINN (PID2019-110305GB-I00). We also thank CIC NanoGune for technical support in OFET characterization measurements.Peer reviewe

    Synthesis of Perylene Imide Diones as Platforms for the Development of Pyrazine Based Organic Semiconductors

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    There is a great interest in peryleneimide (PI)-containing compounds given their unique combination of good electron accepting ability, high abosorption in the visible region, and outstanding chemical, thermal, and photochemical stabilities. Thus, herein we report the synthesis of perylene imide derivatives endowed with a 1,2-diketone functionality (<b>PIDs</b>) as efficient intermediates to easily access peryleneimide (PI)-containing organic semiconductors with enhanced absorption cross-section for the design of tunable semiconductor organic materials. Three processable organic molecular semiconductors containing thiophene and terthiophene moieties, <b>PITa</b>, <b>PITb</b>, and <b>PITT</b>, have been prepared from the novel <b>PIDs</b>. The tendency of these semiconductors for molecular aggregation have been investigated by NMR spectroscopy and supported by quantum chemical calculations. 2D NMR experiments and theoretical calculations point to an antiparallel π-stacking interaction as the most stable conformation in the aggregates. Investigation of the optical and electrochemical properties of the materials is also reported and analyzed in combination with DFT calculations. Although the derivatives presented here show modest electron mobilities of ∼10<sup>–4</sup> cm<sup>2</sup>V<sup>–1</sup>s<sup>–1</sup>, these preliminary studies of their performance in organic field effect transistors (OFETs) indicate the potential of these new building blocks as n-type semiconductors

    Social acceptance of wind and solar power in the Brazilian electricity system

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    Renewable energy is often associated with the production of clean electricity and free of significant adverse impacts. However, several studies have been highlighting the importance of the assessment of social impacts of these technologies, including not only the benefits but also the potential negative aspects most frequently affecting local population. The energy matrix in Brazil is already built up on a renewable system largely supported on hydropower but other technologies with special emphasis on wind power start to have a major role, with a strong growth forecasted for this sector in the coming years. This article discusses the integration of solar and wind power in the Brazilian electricity system focusing on the social awareness and acceptance for the population living in high potential regions. For this, a questionnaire was proposed with the aim of evaluating the level of knowledge of wind and solar power, their social acceptance and perceptions towards cost, local development and environmental impacts. The questionnaire was implemented in an academic institution in the State of Rio Grande do Norte (RN) including students and professors as key actors for the present and future energy policy decision making. The implementation process and the obtained results are described allowing to conclude on the high level of acceptance of solar and wind power in the country and the region, with low evidence of not in my backyard syndrome.The authors wish to acknowledge the support of ALGORITMI research Centre at University of Minho. This work has been supported by COMPETE: POCI-01-0145-FEDER-007043 and FCT-Fundacao para a Ciencia e Tecnologia within the Project Scope: UID/CEC/00319/2013. The authors are grateful to the Rectory of Instituto Federal de Educacao, Ciencia e Tecnologia do Rio Grande do Norte (IFRN) who allowed for the implementation of the survey.info:eu-repo/semantics/publishedVersio

    Reproductive performance of sows submitted to intrauterine insemination Desempenho reprodutivo de matrizes suínas inseminadas pela técnica intrauterina

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    The objective of this study was to evaluate the reproductive performance of sows artificially inseminated by the intrauterine (IAIU) technique. The experiment was arranged in a randomized complete block design, with 300 sows being distributed in five insemination techniques: control, intra-cervical (IAIC) with 3x10(9) spermatozoa/100 mL; intrauterine (IAIU) with 1x10(9) spermatozoa/100 mL; intrauterine with com 1x10(9) spermatozoa/50 mL; intrauterine with 5x10(8) spermatozoa/100 mL; and intrauterine com 5x10(8) spermatozoa/50 mL. The sows submitted to intrauterine insemination presented a farrowing rate of 90.8% and return to estrus rate of 9.2%, which did not differ from the rates obtained by the intra-cervical technique (90.0% and 10.0%, respectively). Total litter size did not differ between the techniques, with the means being from 11.4 to 11.9 piglets at farrowing. Although 4.6% of the sows submitted to intrauterine artificial insemination had difficulty with pipette insertion into the cervix, 100% of them were inseminated. When evaluating semen backflow, no difference was found between the intra-cervical and intrauterine insemination techniques. However, total semen backflow was higher in sows submitted to inter-cervical insemination. No difference was found in the presence of blood between the two methods evaluated. Hence, any of the intrauterine insemination techniques can substitute inter-cervical artificial insemination without damaging the reproductive performance of the animals.<br>Um experimento foi realizado com o objetivo de avaliar o desempenho reprodutivo de matrizes suínas inseminadas pela técnica intrauterina (IAIU). Em um delineamento inteiramente casualizado, 300 fêmeas foram distribuídas em cinco técnicas de inseminação: controle - intracervical (IAIC) com 3x10(9) espermatozoides/100 mL; intrauterina (IAIU) com 1x10(9) espermatozoides/100 mL; intrauterina com 1x10(9) espermatozoides/50 mL; intrauterina com 5x10(8) espermatozoides/100 mL; e intrauterina com 5x10(8) espermatozoides/50 mL. As fêmeas inseminadas pela técnica intrauterina apresentaram taxa de parto de 90,8% e taxa de repetição de estro de 9,2%, que não diferiram das taxas obtidas pela técnica intracervical (90,0% e 10,0%, respectivamente). O total de leitões nascidos não diferiu entre as técnicas, com média geral de 11,4 a 11,9 leitões por parto. Apesar da dificuldade na passagem da pipeta em 4,6% das fêmeas submetidas à inseminação artificial intrauterina, 100% das fêmeas foram inseminadas. Na avaliação da ocorrência de refluxo de sêmen, não houve diferença entre as técnicas de inseminação intracervical e intrauterina. Entretanto, o total de espermatozoides refluídos foi maior nas fêmeas submetidas à inseminação intracervical. A ocorrência de sangramento não diferiu entre as técnicas estudadas. Portanto, qualquer uma das técnicas de inseminação intrauterina pode substituir a inseminação artificial intracervical, pois não comprometem o desempenho reprodutivo dos animais
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