3,915 research outputs found
Centromeres under pressure: Evolutionary innovation in conflict with conserved function
Centromeres are essential genetic elements that enable spindle microtubule attachment for chromosome segregation during mitosis and meiosis. While this function is preserved across species, centromeres display an array of dynamic features, including: (1) rapidly evolving DNA; (2) wide evolutionary diversity in size, shape and organization; (3) evidence of mutational processes to generate homogenized repetitive arrays that characterize centromeres in several species; (4) tolerance to changes in position, as in the case of neocentromeres; and (5) intrinsic fragility derived by sequence composition and secondary DNA structures. Centromere drive underlies rapid centromere DNA evolution due to the “selfish” pursuit to bias meiotic transmission and promote the propagation of stronger centromeres. Yet, the origins of other dynamic features of centromeres remain unclear. Here, we review our current understanding of centromere evolution and plasticity. We also detail the mutagenic processes proposed to shape the divergent genetic nature of centromeres. Changes to centromeres are not simply evolutionary relics, but ongoing shifts that on one side promote centromere flexibility, but on the other can undermine centromere integrity and function with potential pathological implications such as genome instability
Higher-Order Hierarchical Models for the Free Vibration Analysis of Thin-Walled Beams
This paper addresses a free vibration analysis of thin-walled isotropic beams via higher-order refined theories. The unknown kinematic variables are approximated along the beam cross section as a N-order polynomial expansion, where N is a free parameter of the formulation. The governing equations are derived via the dynamic version of the Principle of Virtual Displacements and are written in a unified form in terms of a “fundamental nucleus.” This latter does not depend upon order of expansion of the theory over the cross section. Analyses are carried out through a closed form, Navier-type solution. Simply supported, slender, and short beams are investigated. Besides “classical” modes (such as bending and torsion), several higher modes are investigated. Results are assessed toward three-dimensional finite element solutions. The numerical investigation shows that the proposed Unified Formulation yields accurate results as long as the appropriate approximation order is considered. The accuracy of the solution depends upon the geometrical parameters of the beam
Integrity of the human centromere DNA repeats is protected by CENP-A, CENP-C, and CENP-T
Centromeres are highly specialized chromatin domains that enable chromosome segregation and orchestrate faithful cell division. Human centromeres are composed of tandem arrays of α-satellite DNA, which spans up to several megabases. Little is known about the mechanisms that maintain integrity of the long arrays of α-satellite DNA repeats. Here, we monitored centromeric repeat stability in human cells using chromosome-orientation fluorescent in situ hybridization (CO-FISH). This assay detected aberrant centromeric CO-FISH patterns consistent with sister chromatid exchange at the frequency of 5% in primary tissue culture cells, whereas higher levels were seen in several cancer cell lines and during replicative senescence. To understand the mechanism(s) that maintains centromere integrity, we examined the contribution of the centromere-specific histone variant CENP-A and members of the constitutive centromere-associated network (CCAN), CENP-C, CENP-T, and CENP-W. Depletion of CENP-A and CCAN proteins led to an increase in centromere aberrations, whereas enhancing chromosome missegregation by alternative methods did not, suggesting that CENP-A and CCAN proteins help maintain centromere integrity independently of their role in chromosome segregation. Furthermore, superresolution imaging of centromeric CO-FISH using structured illumination microscopy implied that CENP-A protects α-satellite repeats from extensive rearrangements. Our study points toward the presence of a centromere-specific mechanism that actively maintains α-satellite repeat integrity during human cell proliferation
Diagnosing transient ionization in dynamic events
The present study aims to provide a diagnostic line ratio that will enable
the observer to determine whether a plasma is in a state of transient
ionization. We use the Atomic Data and Analysis Structure (ADAS) to calculate
line contribution functions for two lines, Si IV 1394 A and O IV 1401 A, formed
in the solar transition region. The generalized collisional-radiative theory is
used. It includes all radiative and electron collisional processes, except for
photon-induced processes. State-resolved direct ionization and recombination to
and from the next ionization stage are also taken into account. For dynamic
bursts with a decay time of a few seconds, the Si IV 1394 A line can be
enhanced by a factor of 2-4 in the first fraction of a second with the peak in
the line contribution function occurring initially at a higher electron
temperature due to transient ionization compared to ionization equilibrium
conditions. On the other hand, the O IV 1401 A does not show such any
enhancement. Thus the ratio of these two lines, which can be observed with the
Interface Region Imaging Spectrograph, can be used as a diagnostic of transient
ionization. We show that simultaneous high-cadence observations of two lines
formed in the solar transition region may be used as a direct diagnostic of
whether the observed plasma is in transient ionization. The ratio of these two
lines can change by a factor of four in a few seconds owing to transient
ionization alone.Comment: 3 pages, in press A&
Seeking for the rational basis of the median model: the optimal combination of multi-model ensemble results
International audienceIn this paper we present an approach for the statistical analysis of multi-model ensemble results. The models considered here are operational long-range transport and dispersion models, also used for the real-time simulation of pollutant dispersion or the accidental release of radioactive nuclides. We first introduce the theoretical basis (with its roots sinking into the Bayes theorem) and then apply this approach to the analysis of model results obtained during the ETEX-1 exercise. We recover some interesting results, supporting the heuristic approach called "median model", originally introduced in Galmarini et al. (2004a, b). This approach also provides a way to systematically reduce (and quantify) model uncertainties, thus supporting the decision-making process and/or regulatory-purpose activities in a very effective manner
The supergiant fast X-ray transients XTE J1739-302 and IGR J08408-4503 in quiescence with XMM-Newton
Context. Supergiant fast X-ray transients are a subclass of high mass X-ray
binaries that host a neutron star accreting mass from the wind of its OB
supergiant companion. They are characterized by an extremely pronounced and
rapid variability in X-rays, which still lacks an unambiguous interpretation. A
number of deep pointed observations with XMM-Newton have been carried out to
study the quiescent emission of these sources and gain insight into the
mechanism that causes their X-ray variability. Aims. We continued this study by
using three XMM-Newton observations of the two supergiant fast X-ray transient
prototypes XTEJ1739-302 and IGR J08408-4503 in quiescence. Methods. An in-depth
timing and spectral analysis of these data have been carried out. Results. We
found that the quiescent emission of these sources is characterized by both
complex timing and spectral variability, with multiple small flares occurring
sporadically after periods of lower X-ray emission. Some evidence is found in
the XMM-Newton spectra of a soft component below ~2 keV, similar to that
observed in the two supergiant fast X-ray transients AXJ1845.0-0433 and
IGRJ16207-5129 and in many other high mass X-ray binaries. Conclusions.We
suggest some possible interpretations of the timing and spectral properties of
the quiescent emission of XTEJ1739- 302 and IGR J08408-4503 in the context of
the different theoretical models proposed to interpret the behavior of the
supergiant fast X-ray transients.Comment: 13 pages, 14 figures. Accepted for publication in A&A. V2: Corrected
few typo
Exosomal Protein Deficiencies: How Abnormal RNA Metabolism Results in Childhood-Onset Neurological Diseases.
Defects of RNA metabolism have been increasingly identified in various forms of inherited neurological diseases. Recently, abnormal RNA degradation due to mutations in human exosome subunit genes has been shown to cause complex childhood onset neurological presentations including spinal muscular atrophy, pontocerebellar hypoplasia and myelination deficiencies. This paper summarizes our current knowledge about the exosome in human neurological disease and provides some important insights into potential disease mechanisms
Variable kinematic plate elements coupled via Arlequin method
In this work, plate elements based on different kinematic assumptions and variational principles are combined through the Arlequin method. Computational costs are reduced assuming refined models only in those zones with a quasi-three-dimensional stress field, whereas computationally cheap, low-order elements are used in the remaining parts of the plate. Plate elements are formulated on the basis of a unified formulation (UF). Via UF, higher-order, layer-wise and mixed theories can be easily formulated. Classical theories, such as Kirchhoff's and Reissner's models, can be obtained as particular cases. UF is extended to the Arlequin method to derive the matrices that account for the coupling between different theories. Multi-layered composite plates are investigated. Variable kinematic multiple models solutions are assessed towards mono-model results and three-dimensional exact results. Numerical investigation has shown that Arlequin method in the context of UF effectively couples sub-domains having finite elements based upon different theories, reducing the computational costs without loss of accurac
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