1,721,184 research outputs found
Coarse grained models: the kinetics of motor proteins
No full textMotor proteins are able to transform the chemical energy of ATP hydrolysis into mechanical work that is essential for a variety of tasks in living cells. Major advances in single molecule nanomanipulation have made it possible to measure the displacements of these proteins along linear tracks, and therefore to obtain an approximate description of their kinetics. Discrete and continuous stochastic models are particularly suited to the interpretation of experimental data in this field, since both allow a complicated mechano-chemical process to be coarse grained in relatively few parameters. However both of them present advantages and shortcomings, though usually one model succeeds where the other fails'. We have recently developed a coarse graining procedure, based on a renormalization group approach, that accounts for the force dependence of transition rates in discrete models, bridging a gap between the two stochastic approaches. We discuss the main results obtained with this procedure and possible future directions of investigation
Linkage of lamins to fidelity of gene transcription.
No full textTwo major events are emerging as being involved in the fine regulatory mechanisms that control gene expression through the nuclear envelope/lamina. The first is the linkage of envelope proteins to transcription factors, most of which function as transcriptional repressors. The second is the interplay between nuclear lamina/nuclear envelope proteins and chromatin, through more or less direct interactions with DNA-binding proteins. The first mechanism appears to play a major role in tissue-specific functions, whereas the latter mechanism likely modifies higher-order chromatin organization, thus regulating differentiation and aging. This review highlights the importance of the study of a group of genetic diseases, collectively referred to as laminopathies, to understand the actual role played by lamins in ensuring the fidelity of gene expression and in modulating cell differentiation
An experimental approach to unravel 2D ground resonances: application to an alluvial-sedimentary basin
Full text linkThe study of ground resonances is important to assess seismic site amplification and to infer information on the geometrical and mechanical properties of the resonating structures. 1D- and 2D-type resonances imply different dynamic behavior that can be distinguished by inspecting the individual spectral components of single-station microtremor measurements. Typically, 2D resonance modes develop along cross-sections of deep sediment-filled valleys and consist of longitudinal, transverse and vertical modes that can be identified as spectral peaks when ground motion is recorded parallel to the axes of the valley. In the case of more complex geometries, such as sedimentary basins, resonance modes are more difficult to predict and depend on the unknown complexity of the buried bedrock geometry. We show how a simple signal rotation procedure applied to single-station microtremor recordings reveals the underlying 2D resonance pattern. The method allows assessing the axes of motion of buried geological structures and identifying 2D resonance modes along these axes. Their directionality, frequency and amplitude features are then analyzed to extract information on the bedrock geometry. We test our method in the Bolzano alluvial-sedimentary basin and we observe that apparently complicated resonance patterns may be simplified by locally referring to the simplest description of the phenomenon as 2D resonance of a valley slice. The bedrock morphology can be decomposed into 2D-like geometries, i.e., excavated channels, and the observed resonances develop within cross-sections of these channels
On the time-stability of resonance frequencies in deep basins
Full text linkDetermining the resonance frequencies of sediment-filled basins is important in seismic site effects assessment and to infer information about the geometrical and mechanical properties of the basins. Being intrinsic properties of elastic bodies, resonance frequencies are not expected to change over time, at least in the short term and under small excitations, in this type of basins. By analysing multi-annual time-series at some seismic stations located on markedly alpine and subalpine 2-D basins, we first state under what type of exciting function (ambient noise) these resonances can be identified and with what uncertainty. The analysis will reveal a clear annual and daily oscillation of the resonance frequencies, increasing in the summertime and at daytime (i.e. directly correlated with temperature). We attempt to provide different explanations to this not yet so systematically documented experimental evidence. A clear and unique answer is yet to come
The role of transposable elements activity in aging and their possible involvement in laminopathic diseases
Full text linkEukaryotic genomes contain a large number of transposable elements, part of which are still active and able to transpose in the host genome. Mobile element activation is repressed to avoid deleterious effects, such as gene mutations or chromosome rearrangements. Control of transposable elements includes a variety of mechanisms comprising silencing pathways, which are based on the production of small non-coding RNAs. Silencing can occur either through transposable element RNA degradation or through the targeting of DNA sequences by heterochromatin formation and consequent transcriptional inhibition. Since the important role of the heterochromatin silencing, the gradual loss of heterochromatin marks in constitutive heterochromatin regions during the aging process promotes derepression of transposable elements, which is considered a cause of the progressive increase in genomic instability and of the activation of inflammatory responses. This review provides an overview of the effects of heterochromatin loss on the activity of transposable elements during the aging process and the possible impact on genome function. In this context, we discuss the possible role of the nuclear lamina, a major player in heterochromatin dynamics, in the regulation of transposable element activity and potential implications in laminopathic diseases
Potential therapeutic effects of the MTOR inhibitors for preventing ageing and progeria-related disorders
No full textThe mammalian target of rapamycin (mTOR) pathway is an highly conserved signal transduction axis involved in many cellular processes, such as cell growth, survival, transcription, translation, apoptosis, metabolism, motility and autophagy. Recently, this signalling pathway has come to the attention of the scientific community owing to the unexpected finding that inhibition of mTOR by rapamycin, an antibiotic with immunosuppressant and chemotherapeutic properties, extends lifespan in diverse animal models. Moreover, rapamycin has been reported to rescue the cellular phenotype in a progeroid syndrome [Hutchinson–Gilford Progeria syndrome (HGPS)] that recapitulates most of the traits of physiological ageing. The promising perspectives raised by these results warrant a better understanding of mTOR signalling and the potential applications of mTOR inhibitors to counteract ageing-associated diseases and increase longevity. This review is focused on these issues
Force dependence of the Michaelis constant in a two-state ratchet model for molecular motors
No full textWe present a quantitative analysis of recent data on the kinetics of ATP hydrolysis, which has presented a puzzle regarding the load dependence of the Michaelis constant. Within the Framework of coarse grained two-state ratchet models, our analysis not only explains the puzzling data, but provides a modified Michaelis law, which could be useful as a guide for future experiments
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