Molecular Dynamics of "Fuzzy" Transcriptional Activator-Coactivator Interactions

Transcriptional activation domains (ADs) are generally thought to be intrinsically unstructured, but capable of adopting limited secondary structure upon interaction with a coactivator surface. The indeterminate nature of this interface made it hitherto difficult to study structure/function relationships of such contacts. Here we used atomistic accelerated molecular dynamics (aMD) simulations to study the conformational changes of the GCN4 AD and variants thereof, either free in solution, or bound to the GAL11 coactivator surface. We show that the AD-coactivator interactions are highly dynamic while obeying distinct rules. The data provide insights into the constant and variable aspects of orientation of ADs relative to the coactivator, changes in secondary structure and energetic contributions stabilizing the various conformers at different time points. We also demonstrate that a prediction of α-helical propensity correlates directly with the experimentally measured transactivation potential of a large set of mutagenized ADs. The link between α-helical propensity and the stimulatory activity of ADs has fundamental practical and theoretical implications concerning the recruitment of ADs to coactivators

Computing mean first exit times for stochastic processes using multi-level Monte Carlo

The multi-level approach developed by Giles (2008) can be used to estimate mean first exit times for stochastic differential equations, which are of interest in finance, physics and chemical kinetics. Multi-level improves the computational expense of standard Monte Carlo in this setting by an order of magnitude. More precisely, for a target accuracy of TOL, so that the root mean square error of the estimator is O(TOL), the O(TOL-4) cost of standard Monte Carlo can be reduced to O(TOL-3|log(TOL)|1/2) with a multi-level scheme. This result was established in Higham, Mao, Roj, Song, and Yin (2013), and illustrated on some scalar examples. Here, we briefly overview the algorithm and present some new computational results in higher dimensions

Origin and properties of own error signals of the discrete wavelet transform algorithms

The article presents a method for analyzing the own errors of the discrete wavelet transform algorithms, which are introduced by these algorithms into the output quantities. The presented considerations include determining the origin of the error signals in question and determining their parameters. Both errors resulting from imperfections in the transmittance of the algorithm and those resulting from its implementation in the actual measurement chain were considered

Markedly Divergent Tree Assemblage Responses to Tropical Forest Loss and Fragmentation across a Strong Seasonality Gradient

We examine the effects of forest fragmentation on the structure and composition of tree assemblages within three seasonal and aseasonal forest types of southern Brazil, including evergreen, Araucaria, and deciduous forests. We sampled three southernmost Atlantic Forest landscapes, including the largest continuous forest protected areas within each forest type. Tree assemblages in each forest type were sampled within 10 plots of 0.1 ha in both continuous forests and 10 adjacent forest fragments. All trees within each plot were assigned to trait categories describing their regeneration strategy, vertical stratification, seed-dispersal mode, seed size, and wood density. We detected differences among both forest types and landscape contexts in terms of overall tree species richness, and the density and species richness of different functional groups in terms of regeneration strategy, seed dispersal mode and woody density. Overall, evergreen forest fragments exhibited the largest deviations from continuous forest plots in assemblage structure. Evergreen, Araucaria and deciduous forests diverge in the functional composition of tree floras, particularly in relation to regeneration strategy and stress tolerance. By supporting a more diversified light-demanding and stress-tolerant flora with reduced richness and abundance of shade-tolerant, old-growth species, both deciduous and Araucaria forest tree assemblages are more intrinsically resilient to contemporary human-disturbances, including fragmentation-induced edge effects, in terms of species erosion and functional shifts. We suggest that these intrinsic differences in the direction and magnitude of responses to changes in landscape structure between forest types should guide a wide range of conservation strategies in restoring fragmented tropical forest landscapes worldwide

Stop Turkey from bombing our friends fighting ISIS

Abstract: Kurds have a saying `Kurds have no friends but the mountains`. This time, let`s make the saying wrong

The elections in Turkey : beginning of a new stage in the struggle

Abstract: Erdogan regained power by promising to crush Kurdish aspirations for freedom and by scaring off the liberals

Hvor blev én million arresterede kommunister af?´Archipel GULag II´

Hvor blev én million arresterede kommunister af?´Archipel GULag II

Bite by Bite: Unveiling the Impact of Chewing Sticks on Endovascular Health and Neurovascular Coupling – A Narrative Review

Objective: This paper aims to explore the effects of chewing sticks, such as miswak (Salvadora persica) and neem (Azadirachta indica), on vascular health and neurovascular coupling, assessing their potential benefits for cardiovascular and cognitive functions. Methods: A comprehensive literature review was conducted to analyze existing studies related to the physiological effects of chewing sticks. Emphasis was placed on their impact on vascular health, neurovascular coupling, and the mechanisms behind these effects, including the stimulation of the trigeminal nerve and the release of norepinephrine. Results: Chewing stimulates the trigeminal nerve, which promotes the release of norepinephrine from the locus coeruleus, enhancing vascular dilation and regulating blood pressure. This process supports neurovascular coupling and may protect the blood-brain barrier, thereby improving cerebral circulation and reducing risks associated with cognitive decline and cardiovascular diseases. Additionally, the bioactive compounds found in chewing sticks—such as antioxidants and antimicrobial agents—may help reduce systemic inflammation and promote overall vascular health. Conclusion: Chewing sticks represent a potential cost-effective and accessible strategy for improving cardiovascular and cognitive health, especially in populations with limited healthcare access. While preliminary findings are promising, further research, including clinical trials, is necessary to fully elucidate the therapeutic potential of chewing sticks for enhancing vascular and cognitive functions

A novel technique for fetal heart rate estimation from Doppler ultrasound signal

<p>Abstract</p> <p>Background</p> <p>The currently used fetal monitoring instrumentation that is based on Doppler ultrasound technique provides the fetal heart rate (FHR) signal with limited accuracy. It is particularly noticeable as significant decrease of clinically important feature - the variability of FHR signal. The aim of our work was to develop a novel efficient technique for processing of the ultrasound signal, which could estimate the cardiac cycle duration with accuracy comparable to a direct electrocardiography.</p> <p>Methods</p> <p>We have proposed a new technique which provides the true beat-to-beat values of the FHR signal through multiple measurement of a given cardiac cycle in the ultrasound signal. The method consists in three steps: the dynamic adjustment of autocorrelation window, the adaptive autocorrelation peak detection and determination of beat-to-beat intervals. The estimated fetal heart rate values and calculated indices describing variability of FHR, were compared to the reference data obtained from the direct fetal electrocardiogram, as well as to another method for FHR estimation.</p> <p>Results</p> <p>The results revealed that our method increases the accuracy in comparison to currently used fetal monitoring instrumentation, and thus enables to calculate reliable parameters describing the variability of FHR. Relating these results to the other method for FHR estimation we showed that in our approach a much lower number of measured cardiac cycles was rejected as being invalid.</p> <p>Conclusions</p> <p>The proposed method for fetal heart rate determination on a beat-to-beat basis offers a high accuracy of the heart interval measurement enabling reliable quantitative assessment of the FHR variability, at the same time reducing the number of invalid cardiac cycle measurements.</p