The Acute Effects of Cardiorespiratory Exercise on Telomere-Associated Genes and MicroRNA Expression in Immune Cell Subsets.

The acute effects of cardiorespiratory exercise on telomere-associated genes and microRNA expression in immune cell subsets. CHILTON WL, MARQUES FZ, O’BRIEN BJ, and CHARCHAR F. School of Health Sciences; University of Ballarat; Victoria, Australia. ABSTRACT Telomeres are specialized nucleoprotein structures that protect the ends of linear chromosomes from degradation. Habitual physical activity is positively associated with longer leukocyte telomere length; however the molecular mechanisms underpinning the association are unclear. Human telomerase reverse transcriptase (hTERT) is the rate-limiting component of the telomere extending enzyme telomerase. The effective functioning of the adaptive immune system depends heavily upon the replicative potential of T cells, which is largely determined by telomere length and hTERT expression. Sirtuin 6 (SIRT6) also serves important pro-telomeric functions via an interaction with telomeric chromatin and regulatory roles in genome stabilization and DNA repair. It is unknown if cardiorespiratory exercise acutely regulates mRNA levels of hTERT, SIRT6 or other telomere-associated genes in white blood cells in general and T cell subsets in particular. Additionally, the exercise-induced regulation of microRNAs (short, non-coding RNA molecules that negatively regulate gene expression) with potential telomeric functions is unknown. Twenty-three healthy males (mean age=23.96 ±1.49 years) undertook 30min of treadmill running at 80% of previously determined VO2peak. Blood samples were taken before exercise, immediately post-exercise and 60min post-exercise. White blood cells and flow cytometry-sorted T cell subsets were assessed via quantitative polymerase chain reaction for differential regulation of telomeric genes and microRNAs. Expression levels of hTERT and SIRT6 mRNA were up-regulated following exercise in white blood cells and various T cell subsets (CD4+ naïve, CD4+ memory, CD8+ naïve, and CD8+ memory). Additionally, exercise differentially regulated several genes associated with telomere structure. A total of 56 microRNAs were differentially regulated post-exercise, six of which were investigated for potential telomeric functions. MicroRNAs-186, 636, 15a, and 96 showed significant up-regulation 60min post-exercise. MicroRNAs-186 and 636 showed detectable differential regulation in naïve and memory subsets. Intense cardiorespiratory exercise differentially regulated a host of telomeric genes in white blood cells and T cell subsets. Furthermore, it resulted in differential regulation of 56 microRNAs, some of which have binding potential to telomeric genes. Importantly, we demonstrated cell type-specific expression patterns in telomeric genes and microRNA. These results could have important implications for T cell-dependent immune functions and telomere homeostasis

Born to learn: The inspiration, progress, and future of evolved plastic artificial neural networks

Biological plastic neural networks are systems of extraordinary computational capabilities shaped by evolution, development, and lifetime learning. The interplay of these elements leads to the emergence of adaptive behavior and intelligence. Inspired by such intricate natural phenomena, Evolved Plastic Artificial Neural Networks (EPANNs) use simulated evolution in-silico to breed plastic neural networks with a large variety of dynamics, architectures, and plasticity rules: these artificial systems are composed of inputs, outputs, and plastic components that change in response to experiences in an environment. These systems may autonomously discover novel adaptive algorithms, and lead to hypotheses on the emergence of biological adaptation. EPANNs have seen considerable progress over the last two decades. Current scientific and technological advances in artificial neural networks are now setting the conditions for radically new approaches and results. In particular, the limitations of hand-designed networks could be overcome by more flexible and innovative solutions. This paper brings together a variety of inspiring ideas that define the field of EPANNs. The main methods and results are reviewed. Finally, new opportunities and developments are presented

Soil penetration resistance analysis by multivariate and geostatistical methods

The penetration resistance (PR) is a soil attribute that allows identifies areas with restrictions due to compaction, which results in mechanical impedance for root growth and reduced crop yield. The aim of this study was to characterize the PR of an agricultural soil by geostatistical and multivariate analysis. Sampling was done randomly in 90 points up to 0.60 m depth. It was determined spatial distribution models of PR, and defined areas with mechanical impedance for roots growth. The PR showed a random distribution to 0.55 and 0.60 m depth. PR in other depths analyzed showed spatial dependence, with adjustments to exponential and spherical models. The cluster analysis that considered sampling points allowed establishing areas with compaction problem identified in the maps by kriging interpolation. The analysis with main components identified three soil layers, where the middle layer showed the highest values of PR.La resistencia a la penetración (RP) es un atributo del suelo que permite identificar zonas con restricciones debido a la compactación, que se traduce en impedancia mecánica para el desarrollo de las raíces y en una menor productividad de los cultivos. El objetivo del presente trabajo fue caracterizar la RP de un suelo agrícola, mediante análisis geoestadístico y multivariado. El muestreo se realizó de manera aleatoria en 90 puntos, hasta una profundidad de 0,60 m. Se determinaron los modelos de distribución espacial de la RP y se delimitaron áreas con problemas de impedancia mecánica de las raíces. La RP presentó distribución aleatoria a 0,55 y 0,60 m de profundidad. La RP en las otras profundidades analizadas mostraron dependencia espacial, con ajustes a modelos exponenciales y esféricos. El análisis jerárquico que consideró puntos de muestreo, permitió establecer zonas con problemas de compactación, identificadas en los mapas obtenidos mediante interpolación por kriging. El análisis de componentes principales permitió identificar tres capas de suelo, donde la capa intermedia fue la que presentó los mayores valores de RP

Effect of pH of amine fluoride containing toothpastes on enamel remineralization in vitro

<p>Abstract</p> <p>Background</p> <p>One of the important factors of the demineralization and remineralization equilibrium of enamel is the pH of the surrounding solutions. Effort has been laid in the formulation of different fluoride compounds and the fluoride content in toothpastes but much less is known about the influence of the pH of the toothpastes on their effectiveness. It was therefore the aim of this study to investigate the influence of different pH levels on enamel remineralization in an in vitro experiment using polarization light microscopy and EDX quantitative element analysis.</p> <p>Methods</p> <p>A 5 × 5 mm window on the enamel surface of 40 caries free extracted human premolars was demineralized in a hydroxyethylcellulose solution at pH 4.8. The teeth were divided into 8 groups and the lower half of the window was covered with varnish serving as control. Each group was then immersed in toothpaste slurry containing amine fluoride (1400 ppm) at pH 4.1, 4.5, 5.1 and 6.9 or control toothpaste slurry without fluoride at pH 4.3, 4.7, 5.3 and 7.0. Serial sections were cut through the lesions and investigated with polarization light microscopy and quantitative EDX element analysis.</p> <p>Results</p> <p>The PLM results showed a decreased porous volume of the body of the lesion after incubation with fluoridated toothpaste at pH 4.53 and 5.16. No differences between the experimental window and the control window were found in the other groups. The quantitative element analysis showed no differences in the element content of any of the groups.</p> <p>Conclusion</p> <p>From the results it can be concluded that slightly acidified fluoridated dentifrices may have a certain positive effect on enamel remineralization.</p

Stabilization of global temperature at 1.5°C and 2.0°C: implications for coastal areas

The effectiveness of stringent climate stabilization scenarios for coastal areas in terms of reduction of impacts/adaptation needs and wider policy implications has received little attention. Here we use the Warming Acidification and Sea Level Projector Earth systems model to calculate large ensembles of global sea-level rise (SLR) and ocean pH projections to 2300 for 1.5°C and 2.0°C stabilization scenarios, and a reference unmitigated RCP8.5 scenario. The potential consequences of these projections are then considered for global coastal flooding, small islands, deltas, coastal cities and coastal ecology. Under both stabilization scenarios, global mean ocean pH (and temperature) stabilize within a century. This implies significant ecosystem impacts are avoided, but detailed quantification is lacking, reflecting scientific uncertainty. By contrast, SLR is only slowed and continues to 2300 (and beyond). Hence, while coastal impacts due to SLR are reduced significantly by climate stabilization, especially after 2100, potential impacts continue to grow for centuries. SLR in 2300 under both stabilization scenarios exceeds unmitigated SLR in 2100. Therefore, adaptation remains essential in densely populated and economically important coastal areas under climate stabilization. Given the multiple adaptation steps that this will require, an adaptation pathways approach has merits for coastal areas. This article is part of the theme issue ‘The Paris Agreement: understanding the physical and social challenges for a warming world of 1.5°C above pre-industrial levels’

Splice Isoforms of the Polyglutamine Disease Protein Ataxin-3 Exhibit Similar Enzymatic yet Different Aggregation Properties

Protein context clearly influences neurotoxicity in polyglutamine diseases, but the contribution of alternative splicing to this phenomenon has rarely been investigated. Ataxin-3, a deubiquitinating enzyme and the disease protein in SCA3, is alternatively spliced to encode either a C-terminal hydrophobic stretch or a third ubiquitin interacting motif (termed 2UIM and 3UIM isoforms, respectively). In light of emerging insights into ataxin-3 function, we examined the significance of this splice variation. We confirmed neural expression of several minor 5′ variants and both of the known 3′ ataxin-3 splice variants. Regardless of polyglutamine expansion, 3UIM ataxin-3 is the predominant isoform in brain. Although 2UIM and 3UIM ataxin-3 display similar in vitro deubiquitinating activity, 2UIM ataxin-3 is more prone to aggregate and more rapidly degraded by the proteasome. Our data demonstrate how alternative splicing of sequences distinct from the trinucleotide repeat can alter properties of the encoded polyglutamine disease protein and thereby perhaps contribute to selective neurotoxicity

Modulation of Heat Shock Transcription Factor 1 as a Therapeutic Target for Small Molecule Intervention in Neurodegenerative Disease

A yeast-based small molecule screen identifies a novel activator of human HSF1 and protein chaperone expression and which appears to alleviate the toxicity of protein misfolding diseases