DNA methylation: a historical perspective

In 1925, 5-methylcytosine was first reported in bacteria. However, its biological importance was not intuitive for several decades. After this initial lag, the ubiquitous presence of this methylated base emerged across all domains of life and revealed a range of essential biological functions. Today, we are armed with the knowledge of the key factors that establish, maintain, and remove DNA methylation and have access to a staggering and rapidly growing number of base-resolution methylation maps. Despite this, several fundamental details about the precise role and interpretation of DNA methylation patterns remain under investigation. Here, we review the field of DNA methylation from its beginning to present day, with an emphasis on findings in mammalian systems, and point the reader to select experiments that form the foundation of this field

Loss of correlation between HIV viral load and CD4+ T-cell counts in HIV/HTLV-1 co-infection in treatment naive Mozambican patients

Seven hundred and four HIV-1/2-positive, antiretroviral therapy (ART) naïve patients were screened for HTLV-1 infection. Antibodies to HTLV-1 were found in 32/704 (4.5%) of the patients. Each co-infected individual was matched with two HIV mono-infected patients according to World Health Organization clinical stage, age +/-5 years and gender. Key clinical and laboratory characteristics were compared between the two groups. Mono-infected and co-infected patients displayed similar clinical characteristics. However, co-infected patients had higher absolute CD4+ T-cell counts (P = 0.001), higher percentage CD4+ T-cell counts (P < 0.001) and higher CD4/CD8 ratios (P < 0.001). Although HIV plasma RNA viral loads were inversely correlated with CD4+ T-cell-counts in mono-infected patients (P < 0.0001), a correlation was not found in co-infected individuals (P = 0.11). Patients with untreated HIV and HTLV-1 co-infection show a dissociation between immunological and HIV virological markers. Current recommendations for initiating ART and chemoprophylaxis against opportunistic infections in resource-poor settings rely on more readily available CD4+ T-cell counts without viral load parameters. These guidelines are not appropriate for co-infected individuals in whom high CD4+ T-cell counts persist despite high HIV viral load states. Thus, for co-infected patients, even in resource-poor settings, HIV viral loads are likely to contribute information crucial for the appropriate timing of ART introduction

An Integrated In Vitro–In Silico Approach for Silver Nanoparticle Dosimetry in Cell Cultures

Potential human and environmental hazards resulting from the exposure of living organisms to silver nanoparticles (Ag NPs) have been the subject of intensive discussion in the last decade. Despite the growing use of Ag NPs in biomedical applications, a quantification of the toxic effects as a function of the total silver mass reaching cells (namely, target cell dose) is still needed. To provide a more accurate dose-response analysis, we propose a novel integrated approach combining well-established computational and experimental methodologies. We first used a particokinetic model (ISD3) for providing experimental validation of computed Ag NP sedimentation in static-cuvette experiments. After validation, ISD3 was employed to predict the total mass of silver reaching human endothelial cells and hepatocytes cultured in 96 well plates. Cell viability measured after 24 h of culture was then related to this target cell dose. Our results show that the dose perceived by the cell monolayer after 24 h of exposure is around 85% lower than the administered nominal media concentration. Therefore, accurate dosimetry considering particle characteristics and experimental conditions (e.g., time, size and shape of wells) should be employed for better interpreting effects induced by the amount of silver reaching cells

Solar-like oscillations of semiregular variables

Oscillations of the Sun and solar-like stars are believed to be excited stochastically by convection near the stellar surface. Theoretical modeling predicts that the resulting amplitude increases rapidly with the luminosity of the star. Thus one might expect oscillations of substantial amplitudes in red giants with high luminosities and vigorous convection. Here we present evidence that such oscillations may in fact have been detected in the so-called semiregular variables, extensive observations of which have been made by amateur astronomers in the American Association for Variable Star Observers (AAVSO). This may offer a new opportunity for studying the physical processes that give rise to the oscillations, possibly leading to further information about the properties of convection in these stars.Comment: Astrophys. J. Lett., in the press. Processed with aastex and emulateap

Automatic adjustment of tire inflation pressure through an intelligent CTIS: Effects on the vehicle lateral dynamic behavior

The paper investigates the effect of tire inflation pressure on the lateral dynamics of a passenger car, and presents a possible control-oriented methodology aimed at adapting tire pressure to the current vehicle loading condition targeting a reference characteristic. Starting from the tire characteristics at several inflation pressure levels, the paper investigates the effect of changing selectively tire pressure on each of the two axles, through theoretical calculation of the curvature gain based on the computation of the derivatives of stability, and compares the obtained sensitivity to the results of a multibody simulation model validated through on-track tests. Finally, the work presents a possible algorithm that could be implemented on-board vehicle ECU to provide, for the current loading condition of the vehicle, a tire pressure combination that targets a specific lateral dynamics characteristic. The algorithm is intended as part of the control logic of an intelligent Central Tire Inflation System (CTIS) able to adjust automatically tire pressure according to the actual vehicle working conditions

Análise da composição físico-química de salames coloniais e bacons comercializados no município de Concórdia, Santa Catarina.

Projeto/Plano de Ação: 01.06.06.001

Functionalized Enzyme-Responsive Biomaterials to Model Tissue Stiffening in vitro

The mechanical properties of the cellular microenvironment play a crucial role in modulating cell function, and many pathophysiological processes are accompanied by variations in extracellular matrix (ECM) stiffness. Lysyl oxidase (LOx) is one of the enzymes involved in several ECM-stiffening processes. Here, we engineered poly(ethylene glycol) (PEG)-based hydrogels with controlled mechanical properties in the range typical of soft tissues. These hydrogels were functionalized featuring free primary amines, which allows an additional chemical LOx-responsive behavior with increase in crosslinks and hydrogel elastic modulus, mimicking biological ECM-stiffening mechanisms. Hydrogels with elastic moduli in the range of 0.5–4 kPa were obtained after a first photopolymerization step. The increase in elastic modulus of the functionalized and enzyme-responsive hydrogels was also characterized after the second-step enzymatic reaction, recording an increase in hydrogel stiffness up to 0.5 kPa after incubation with LOx. Finally, hydrogel precursors containing HepG2 (bioinks) were used to form three-dimensional (3D) in vitro models to mimic hepatic tissue and test PEG-based hydrogel biocompatibility. Hepatic functional markers were measured up to 7 days of culture, suggesting further use of such 3D models to study cell mechanobiology and response to dynamic variation of hydrogels stiffness. The results show that the functionalized hydrogels presented in this work match the mechanical properties of soft tissues, allow dynamic variations of hydrogel stiffness, and can be used to mimic changes in the microenvironment properties of soft tissues typical of inflammation and pathological changes at early stages (e.g., fibrosis, cancer)

Influência da adubação nitrogenada e da idade de corte sobre o rendimento forrageiro do capim-elefante.

Resumo: O experimento foi realizado em Parnaíba, para avaliar os efeitos de três doses de nitrogênio (150; 300 e 450 kg de N.ha-1) e cinco idades de corte (28; 35; 42; 56 e 84 dias) sobre a altura, teores de matéria seca e rendimento forrageiro do capim-elefante cv. Napier. O delineamento experimental foi em blocos casualizados, em parcelas subdivididas, com quatro repetições. A altura da planta recebeu influência significativa da idade e da aplicação de 450 kg de N.ha-1, enquanto os teores de matéria seca foram influenciados apenas pela idade da planta. Os rendimentos de matéria seca foram significativamente incrementados (P 0,05) da produção aos 28 dias (3,28 t.ha-1). A aplicação de 450 kg de N.ha-1 implicou no maior rendimento de forragem (8,82 t.ha-1), tendo sido estatisticamente semelhante à aplicação de 300 kg de N.ha-1 (7,84 t.ha-1 ), a qual não diferiu (P > 0,05) da aplicação de 150 kg de N.ha-1 (7,75 t.ha-1). A eficiência do nitrogênio aplicado, independentemente da idade de corte, foi inversamente proporcional às doses aplicadas: 51,66; 26,13 e 19,6 kg de MS.kg-1 de N, respectivamente para 150, 300 e 450 kg de N.ha-1. Influence of the nitrogen fertilization and of the cut age on the forage yield of the elephant grass. Abstract - The study was carried out in Parnaíba, Brazil, aiming to evaluate the effects of three levels of nitrogen doses (150; 300 and 450 kgN.ha -1 ) and five plant age at cutting (28; 35; 42; 56 and 84 days) on height, dry matter, and biomass yield of elephant grass, cv. Napier. The experimental design was in complete randomized blocks, with 4 replications. Plant height was significantly influenced by plant age and nitrogen dose (450 kgN.ha -1 ). Plant dry matter, however, was influenced only by plant age. Plant dry matter yield significantly increased (P < 0.05) in line with plant age at cutting, with age at cutting of 84 days yielding the best results (18.93 t.ha -1 ), followed by 56 days (9.48 t.ha -1 ), and 42 days (5.02 t.ha -1 ). Plant biomass obtained by cutting at 35 days (3.96 t.ha -1 ) did not differ from cutting at 28 days (3.28 t.ha -1 ). Application of 450 kgN.ha -1 resulted in greater biomass yield (8.82 t.ha -1 ), and did not differ (P < 0.05) from 300 kgN.ha -1 (7.84 t.ha -1 ), which in turn did not differ (P < 0.05) from 150 kgN.ha -1 (7.75 t.ha -1 ). Nitrogen application efficiency (51.66; 26.13 and 19.6 kgDM.kg -1 .N), regardless of plant age at cutting, was inversely proportional to nitrogen doses (150; 300 and 450 kgN.ha -1 )