共查询到20条相似文献，搜索用时 31 毫秒
1.
Zhihua Cai Yun Xia Zheng Bao 《Computer methods in biomechanics and biomedical engineering》2019,22(2):169-179
To better understand head injuries, human head finite element (FE) models have been reported in the literature. In scenarios where the head is directly impacted and measurements of head accelerations are not available, a high-quality skull model, as well as a high-quality brain model, is needed to predict the effect of impact on the brain through the skull. Furthermore, predicting cranial bone fractures requires comprehensively validated skull models. Lastly, high-quality meshes for both the skull and brain are needed for accurate strain/stress predictions across the entire head. Hence, we adopted a multi-block approach to develop hexahedral meshes for the brain, skull, and scalp simultaneously, a first approach in its kind. We then validated our model against experimental data of brain pressures (Nahum et al., 1977) and comprehensive skull responses (Yoganandan et al., 1995, Yoganandan et al., 2004, and Raymond et al., 2009). We concluded that a human head FE model was developed with capabilities to predict blunt- and ballistic-impact-induced skull fractures and pressure-related brain injuries. 相似文献
2.
The existence of extrema, maximum and/or minimum and negative gradients of melting curves observed for several elements at high pressure is investigated by molecular dynamics simulation using the two-species model (TSM) proposed by Ogura et al. [1]. TSM is a model which imitates the change in the electronic structure of an atom in terms of a species change in particles. The TSM phase diagram has two solid phases and one liquid phase with a solid–solid–liquid triple point which corresponds to the melting curve minimum. The melting curve has both a maximum and a minimum, and the gradient of the melting curve is negative between these extrema. These peculiar melting curve properties and phase diagram are common to alkali metals and some other elements. 相似文献
3.
Historically, the observation of naturally occurring cases of prion disease led to the classification of different susceptibility grades and to the designation of prion resistant species. However, the development of highly efficient in vitro prion propagation systems and the generation of ad hoc transgenic models allowed determining that leporidae and equidae families have been erroneously considered resistant to prion infection. On the contrary, similar approaches revealed an unexpected high level of resistance of the canidae family. In PLoS Pathogens [1], we describe experiments directed toward elucidating which are the determinants of the alleged prion resistance of this family. Studies based on the sequence of the canine prion protein coupled with structural in silico analysis identified a key residue probably implicated in this resistance. Cell and brain-based PMCA highlighted that the presence of aspartic or glutamic acid at codon 163 of the canid PrP, strongly inhibits prion replication in vitro. Transgenic animals carrying this substitution in mouse PrP were resistant to prion infection after intracerebral challenge with different mouse prion strains. The confirmation of the importance of this substitution and its exclusivity in this family, suggests it could have been evolutionarily favored, due to their diet based on carrion and small ruminants. 相似文献
4.
The transitions between phases of the cell cycle have evolved to be robust and switch-like, which ensures temporal separation of DNA replication, sister chromatid separation, and cell division. Mathematical models describing the biochemical interaction networks of cell cycle regulators attribute these properties to underlying bistable switches, which inherently generate robust, switch-like, and irreversible transitions between states. We have recently presented new mathematical models for two control systems that regulate crucial transitions in the cell cycle: mitotic entry and exit,1 and the mitotic checkpoint.2 Each of the two control systems is characterized by two interlinked bistable switches. In the case of mitotic checkpoint control, these switches are mutually activating, whereas in the case of the mitotic entry/exit network, the switches are mutually inhibiting. In this Perspective we describe the qualitative features of these regulatory motifs and show that having two interlinked bistable mechanisms further enhances robustness and irreversibility. We speculate that these network motifs also underlie other cell cycle transitions and cellular transitions between distinct biochemical states. 相似文献
5.
S. Dash A. Singh A. K. Bhatia S. Jayakumar A. Sharma S. Singh 《Animal biotechnology》2018,29(2):129-135
In total 52 samples of Sahiwal (19), Tharparkar (17), and Gir (16) were genotyped by using BovineHD SNP chip to analyze minor allele frequency (MAF), genetic diversity, and linkage disequilibrium among these cattle. The common SNPs of BovineHD and 54K SNP Chips were also extracted and evaluated for their performance. Only 40%?50% SNPs of these arrays was found informative for genetic analysis in these cattle breeds. The overall mean of MAF for SNPs of BovineHD SNPChip was 0.248?±?0.006, 0.241?±?0.007, and 0.242?±?0.009 in Sahiwal, Tharparkar and Gir, respectively, while that for 54K SNPs was on lower side. The average Reynold’s genetic distance between breeds ranged from 0.042 to 0.055 based on BovineHD Beadchip, and from 0.052 to 0.084 based on 54K SNP Chip. The estimates of genetic diversity based on HD and 54K chips were almost same and, hence, low density chip seems to be good enough to decipher genetic diversity of these cattle breeds. The linkage disequilibrium started decaying (r2?相似文献
6.
Sequestration of aggregates into specialized deposition sites occurs in many species across all kingdoms of life ranging from bacteria to mammals and is commonly believed to have a cytoprotective function. Yeast cells possess at least 3 different spatially separated deposition sites, one of which is termed “Insoluble Protein Deposit (IPOD)” and harbors amyloid aggregates. We have recently discovered that recruitment of amyloid aggregates to the IPOD uses an actin cable based recruitment machinery that also involves vesicular transport.1 Here we discuss how different proteins known to be involved in vesicular transport processes to the vacuole might act to guide amyloid aggregates to the IPOD. These factors include the Myosin V motor protein Myo2 involved in transporting vacuolar vesicles along actin cables, the transmembrane protein Atg9 involved in the recruitment of large precursor hydrolase complexes to the vacuole, the phosphatidylinositol/ phosphatidylcholine (PI/PC) transfer protein Sec 14 and the SNARE chaperone Sec 18. Furthermore, we present new data suggesting that the yeast dynamin homolog Vps1 is also crucial for faithful delivery of the amyloid model protein PrD-GFP to the IPOD. This is in agreement with a previously identified role for Vps1 in recruitment of heat-denatured aggregates to a perivacuolar deposition site.2 相似文献
7.
Irene Gallina Signe Korbo Christiansen Rune Troelsgaard Pedersen Michael Lisby 《Cell cycle (Georgetown, Tex.)》2016,15(2):176-183
Maintenance of genome integrity is crucial to avoid cancer and other genetic diseases. Thus faced with DNA damage, cells mount a DNA damage response to avoid genome instability. The DNA damage response is partially inhibited during mitosis presumably to avoid erroneous processing of the segregating chromosomes. Yet our recent study shows that TopBP1-mediated DNA processing during mitosis is highly important to reduce transmission of DNA damage to daughter cells.1 Here we provide an overview of the DNA damage response and DNA repair during mitosis. One role of TopBP1 during mitosis is to stimulate unscheduled DNA synthesis at underreplicated regions. We speculated that such genomic regions are likely to hold stalled replication forks or post-replicative gaps, which become the substrate for DNA synthesis upon entry into mitosis. Thus, we addressed whether the translesion pathways for fork restart or post-replicative gap filling are required for unscheduled DNA synthesis in mitosis. Using genetics in the avian DT40 cell line, we provide evidence that unscheduled DNA synthesis in mitosis does not require the translesion synthesis scaffold factor Rev1 or PCNA ubiquitylation at K164, which serve to recruit translesion polymerases to stalled forks. In line with this finding, translesion polymerase η foci do not colocalize with TopBP1 or FANCD2 in mitosis. Taken together, we conclude that TopBP1 promotes unscheduled DNA synthesis in mitosis independently of the examined translesion polymerases. 相似文献
8.
The influence of the geometry of the porcine cornea on the biomechanical response of inflation tests
Anna Pandolfi Federica Boschetti 《Computer methods in biomechanics and biomedical engineering》2013,16(1):64-77
To withstand the high probability of success, the growing diffusion of laser surgery for the correction of visual defects, corneal surgeons are regarding with interest numerical tools able to provide reliable predictions of the intervention outcomes. The main obstacle to the definition of a predictive numerical instrument is the objective difficulty in evaluating the in vivo mechanical properties of the human cornea. In this study, we assess the ability of a parametrised numerical model of the cornea (Pandolfi and Manganiello 2006) to describe individual pressurisation tests on whole porcine corneas once the mechanical parameters of the model have been calibrated over average data. We also aim at estimating the sensitivity of the mechanical response with the variation of basic geometrical parameters, such as the central corneal thickness, the curvature and the in-plane diameter. We conclude that the actual geometry of a cornea has a minor role in the overall mechanical response, and therefore the material properties must be considered carefully and individually in any numerical application. This study makes use of the data obtained from a wide experimental program, where a set of 21 porcine corneas has been fully characterised in terms of mechanical and geometrical properties (Boschetti et al. 2012). 相似文献
9.
《朊病毒》2013,7(6):405-411
ABSTRACTWithin the mammalian prion field, the existence of recombinant prion protein (PrP) conformers with self-replicating (ie. autocatalytic) activity in vitro but little to no infectious activity in vivo challenges a key prediction of the protein-only hypothesis of prion replication – that autocatalytic PrP conformers should be infectious. To understand this dissociation of autocatalysis from infectivity, we recently performed a structural and functional comparison between a highly infectious and non-infectious pair of autocatalytic recombinant PrP conformers derived from the same initial prion strain.1 We identified restricted, C-terminal structural differences between these 2 conformers and provided evidence that these relatively subtle differences prevent the non-infectious conformer from templating the conversion of native PrPC substrates containing a glycosylphosphatidylinositol (GPI) anchor.1 In this article we discuss a model, consistent with these findings, in which recombinant PrP, lacking post-translational modifications and associated folding constraints, is capable of adopting a wide variety of autocatalytic conformations. Only a subset of these recombinant conformers can be adopted by post-translationally modified native PrPC, and this subset represents the recombinant conformers with high specific infectivity. We examine this model's implications for the generation of highly infectious recombinant prions and the protein-only hypothesis of prion replication. 相似文献
10.
Sabine Elowe 《Cell cycle (Georgetown, Tex.)》2017,16(8):746-748
Tyrosine phosphorylation is rare, representing only about 0.5% of phosphorylations in the cell under basal conditions. While mitogenic tyrosine kinase signaling has been extensively explored, the role of phosphotyrosine signaling across the cell cycle and in particular during mitosis is poorly understood.
Two recent, independent studies tackled this question from different angles to reveal exciting new insights into the role of this modification during cell division. Caron et al.1 exploited mitotic phosphoproteomics data sets to determine the extent of mitotic tyrosine phosphorylation, and St-Denis et al.2 identified protein tyrosine phosphatases from all subfamilies as regulators of mitotic progression or spindle formation. These studied collectively revealed that tyrosine phosphorylation may play a more prominent and active role in mitotic progression than previously appreciated. 相似文献
11.
《Journal of biological dynamics》2013,7(2):117-130
We address several conjectures raised in Cantrell et al. [Evolution of dispersal and ideal free distribution, Math. Biosci. Eng. 7 (2010), pp. 17–36 [9]] concerning the dynamics of a diffusion–advection–competition model for two competing species. A conditional dispersal strategy, which results in the ideal free distribution of a single population at equilibrium, was found in Cantrell et al. [9]. It was shown in [9] that this special dispersal strategy is a local evolutionarily stable strategy (ESS) when the random diffusion rates of the two species are equal, and here we show that it is a global ESS for arbitrary random diffusion rates. The conditions in [9] for the coexistence of two species are substantially improved. Finally, we show that this special dispersal strategy is not globally convergent stable for certain resource functions, in contrast with the result from [9], which roughly says that this dispersal strategy is globally convergent stable for any monotone resource function. 相似文献
12.
Benjamin Boëns Tan-Sothea Ouk Yves Champavier Rachida Zerrouki 《Nucleosides, nucleotides & nucleic acids》2015,34(7):500-514
This paper describes the synthesis of new click-generated nitrogen mustards and their biological evaluation. By using the copper-catalyzed azide-alkyne cycloaddition (CuAAC) reaction, we managed to synthesize eight new nitrogen mustards. This strategy paves the way for the synthesis of a new family of nitrogen mustard, with an important structural variability. Furthermore, we studied the biological activity of synthesized compounds by testing their cytotoxicity on four representative cancer cell lines A431, JURKAT, K562, and U266. One structure, 1-benzyl-4-(N,N-di-2-chloroethylaminomethyl)-1H-[1,2,3]triazole, showed an interesting cytotoxic effect. 相似文献
13.
Disulfide linkage is critical to protein folding and structural stability. The location of disulfide linkages for antibodies is routinely discovered by comparing the chromatograms of the reduced and non-reduced peptide mapping with location identification confirmed by collision-induced dissociation (CID) mass spectrometry (MS)/MS. However, CID product spectra of disulfide-linked peptides can be difficult to interpret, and provide limited information on the backbone region within the disulfide loop. Here, we applied an electron-transfer dissociation (ETD)/CID combined fragmentation method that identifies the disulfide linkage without intensive LC comparison, and yet maps the disulfide location accurately. The native protein samples were digested using trypsin for proteolysis. The method uses RapiGest SF Surfactant and obviates the need for reduction/alkylation and extensive sample manipulation. An aliquot of the digest was loaded onto a C4 analytical column. Peptides were gradient-eluted and analyzed using a Thermo Scientific LTQ Orbitrap Elite mass spectrometer for the ETD-triggered CID MS3 experiment. Survey MS scans were followed by data-dependent scans consisting of ETD MS2 scans on the most intense ion in the survey scan, followed by 5 MS3 CID scans on the 5 most intense ions in the ETD MS2 scan. We were able to identify the disulfide-mediated structural variants A and A/B forms and their corresponding disulfide linkages in an immunoglobulin G2 monoclonal antibody with λ light chain (IgG2λ), where the location of cysteine linkages were unambiguously determined. 相似文献
14.
All known splice isoforms of vascular endothelial growth factor A (VEGF-A) can bind to the receptor tyrosine kinases VEGFR-1 and VEGFR-2. We focus here on VEGF-A121a and VEGF-A165a, two of the most abundant VEGF-A splice isoforms in human tissue1, and their ability to bind the Neuropilin co-receptors NRP1 and NRP2. The Neuropilins are key vascular, immune, and nervous system receptors on endothelial cells, neuronal axons, and regulatory T cells respectively. They serve as co-receptors for the Plexins in Semaphorin binding on neuronal and vascular endothelial cells, and for the VEGFRs in VEGF binding on vascular and lymphatic endothelial cells, and thus regulate the initiation and coordination of cell signaling by Semaphorins and VEGFs.2 There is conflicting evidence in the literature as to whether only heparin-binding VEGF-A isoforms – that is, isoforms with domains encoded by exons 6 and/or 7 plus 8a – bind to Neuropilins on endothelial cells. While it is clear that VEGF-A165a binds to both NRP1 and NRP2, published studies do not all agree on the ability of VEGF-A121a to bind NRPs. Here, we review and attempt to reconcile evidence for and against VEGF-A121a binding to Neuropilins. This evidence suggests that, in vitro, VEGF-A121a can bind to both NRP1 and NRP2 via domains encoded by exons 5 and 8a; in the case of NRP1, VEGF-A121a binds with lower affinity than VEGF-A165a. In in vitro cell culture experiments, both NRP1 and NRP2 can enhance VEGF-A121a-induced phosphorylation of VEGFR2 and downstream signaling including proliferation. However, unlike VEGFA-165a, experiments have shown that VEGF-A121a does not ‘bridge’ VEGFR2 and NRP1, i.e. it does not bind both receptors simultaneously at their extracellular domain. Thus, the mechanism by which Neuropilins potentiate VEGF-A121a-mediated VEGFR2 signaling may be different from that for VEGF-A165a. We suggest such an alternate mechanism: interactions between NRP1 and VEGFR2 transmembrane (TM) and intracellular (IC) domains. 相似文献
15.
16.
Background: Sporadic fatal insomnia (sFI) is a rapid progressive neurodegenerative disease characterised by gradual to perpetual insomnia, followed by dysautonomia, coma and death.1 The cause of sFI was recently mapped to a mutation in a protein, the prion, found in the human brain. It is the unfolding of the prion that leads to the generation of toxic oligomers that destroy brain tissue and function. Recent studies have confirmed that a methionine mutation at codon 129 of the human Prion is characteristic of sFI. Current treatment slows down the progression of the disease, but no cure has been found, yet. Methods: We used Molecular Docking and Molecular Dynamics simulation methods, to study the toxic Fatal-Insomnia-prion conformations at local unfolding. The idea was to determine these sites and to stabilise these regions against unfolding and miss-folding, using a small ligand, based on a phenothiazine "moiety". Conclusion: As a result we here discuss current fatal insomnia therapy and present seven novel possible compounds for in vitro and in vivo screening. 相似文献
17.
Mallory B. Scott 《Channels (Austin, Tex.)》2017,11(6):555-573
Type two voltage gated calcium (CaV2) channels are the primary mediators of neurotransmission at neuronal presynapses, but their function at neural soma is also important in regulating excitability.1 Mechanisms that regulate CaV2 channel expression at synapses have been studied extensively, which motivated us to perform similar studies in the soma. Rat sympathetic neurons from the superior cervical ganglion (SCG) natively express CaV2.2 and CaV2.3.2 We noted previously that heterologous expression of CaV2.1 but not CaV2.2 results in increased calcium current in SCG neurons.3 In the present study, we extended these observations to show that both CaV2.1 and CaV2.3 expression resulted in increased calcium currents while CaV2.2 expression did not. Further, CaV2.1 could displace native CaV2.2 channels, but CaV2.3 expression could not. Heterologous expression of the individual accessory subunits α2δ-1, α2δ-2, α2δ-3, or β4 alone failed to increase current density, suggesting that the calcium current ceiling when CaV2.2 was over-expressed was not due to lack of these subunits. Interestingly, introduction of recombinant α2δ subunits produced surprising effects on displacement of native CaV2.2 by recombinant channels. Both α2δ-1 and α2δ-2 seemed to promote CaV2.2 displacement by recombinant channel expression, while α2δ-3 appeared to protect CaV2.2 from displacement. Thus, we observe a selective prioritization of CaV channel functional expression in neurons by specific α2δ subunits. These data highlight a new function for α2δ subtypes that could shed light on subtype selectivity of CaV2 membrane expression. 相似文献
18.
The enzymatic oxidization of dissolved Fe(II) to Fe(III) by neutrophilic Fe-oxidizing bacteria plays a significant role in biological cycling of iron by inducing the precipitation of Fe(III) oxyhydroxide in aqueous environments. Among the diverse neutrophilic Fe-oxidizing bacteria, the genus Gallionella has received wide attention for its production of unique twisted extracellular stalks. Hallberg and Tai (2014) recently reported the detection of multi-wall carbon nanotubes on the twisted-stalks, and they viewed those carbon nanotubes as being biologically produced by Gallionella. We scrutinized Gallionella-produced biofilms collected from natural environments by scanning electron microscopy and high-resolution transmission electron microscopy. Ferrihydrite and lepidocrocite were the only nano-scaled minerals observed on the stalk, while there were nanometer-sized sheet-like graphitic contaminants on the grid in the vicinity of the sample which showed the same morphology as Hallberg and Tai (2014) observed. Moreover, similar materials on an empty grid and a grid loaded with randomly selected synthesized materials were also observed. Based on the current knowledge of carbon nanotube syntheses, none of the three known synthesizing methods including root-growth, rolling-up and bottom-up could be biochemically produced by any life because of the significant kinetic and energy obstacles. The carbon nanomaterials reported by Hallberg and Tai (2014) were clearly contaminations from amorphous carbon film on the grids for holding samples for transmission electron microscopic observations. 相似文献
19.
Christopher J. Derrick 《Cell cycle (Georgetown, Tex.)》2017,16(1):23-32
Localized mRNA translation is a widespread mechanism for targeting protein synthesis, important for cell fate, motility and pathogenesis. In Drosophila, the spatiotemporal control of gurken/TGF-α mRNA translation is required for establishing the embryonic body axes. A number of recent studies have highlighted key aspects of the mechanism of gurken mRNA translational control at the dorsoanterior corner of the mid-stage oocyte. Orb/CPEB and Wispy/GLD-2 are required for polyadenylation of gurken mRNA, but unlocalized gurken mRNA in the oocyte is not fully polyadenylated.1 At the dorsoanterior corner, Orb and gurken mRNA have been shown to be enriched at the edge of Processing bodies, where translation occurs.2 Over-expression of Orb in the adjacent nurse cells, where gurken mRNA is transcribed, is sufficient to cause mis-expression of Gurken protein.3 In orb mutant egg chambers, reducing the activity of CK2, a Serine/Threonine protein kinase, enhances the ventralized phenotype, consistent with perturbation of gurken translation.4 Here we show that sites phosphorylated by CK2 overlap with active Orb and with Gurken protein expression. Together with our new findings we consolidate the literature into a working model for gurken mRNA translational control and review the role of kinases, cell cycle factors and polyadenylation machinery highlighting a multitude of conserved factors and mechanisms in the Drosophila egg chamber. 相似文献
20.
Andrew Jackson 《Historical Biology》2013,25(6):699-701
Considerable controversy surrounds the extinction date for the dodo (Raphus cucullatus), and the last uncontrovertibly confirmed sighting is ascribed to Volkert Evertsz on an islet off Mauritius in 1662. Nevertheless, both Roberts and Solow (2003), using a statistical technique, and Hume et al. (2004), drawing on Lamotius' hunting diaries (1685–1688), place the extinction date as late as 1690 and 1693, respectively. A well-known account of Benjamin Harry from 1681 seems to have been frequently dismissed as unreliable or anecdotal. Our purpose here is to provide new background information on Harry's scientific credentials that adds considerable credence to his 1681 report and thus adds to the likelihood of a late date for the dodo's demise, in agreement with the 1690 lower bound. 相似文献