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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.
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?0.2) at 140?kb inter-marker distance and, hence, a 20K low density customized SNP array from HD chip could be designed for genomic selection in these cattle else the 54K Bead Chip as such will be useful. 相似文献
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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
6.
The Inter-Tribal Fisheries and Assessment Program (ITFAP) of the Chippewa Ottawa Resource Authority (CORA) in Sault Ste. Marie, Michigan, has been monitoring contaminant concentrations in the fillet portions of lake trout (Salvelinus namaycush) and lake whitefish (Coregonus clupeaformis) from the waters of lakes Superior, Huron, and Michigan since 1991. The primary purpose of this article is to present a risk quantification of methylmercury (MeHg) that is adjusted for nutritional benefit, originally presented by Ginsberg and Toal (2009, 2015) on trends in contaminant concentrations in fillet portions of these commercial fish that we recently reported in Dellinger et al. (2014). Both species of fish caught by tribal fishermen showed clear benefits to cardiovascular health and infant neurodevelopment if consumed at a rate of six ounces per week. However, other popularly consumed fish such as cod, tuna, and tilapia are estimated to have only marginal benefit or net negative effects on cardiovascular health and infant neurodevelopment. This dynamic assessment of benefits and risks further demonstrates the importance of traditionally caught fish in tribal health. 相似文献
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ABSTRACT One proven strategy to help students make sense of abstract concepts is to sequence instruction so students have exploratory opportunities to investigate science before being introduced to new science explanations (Abraham and Renner 1986; Renner, Abraham, and Birnie 1988). To help physical science teachers make sense of how to effectively sequence lessons, this article summarizes our experiences using an exploration–explanation sequence of instruction to teach Bernoulli's principle to prospective middle and secondary science teachers in a science methods course. We use demonstrations during our Bernoulli unit to help students go back and forth between their observations of phenomenon and what occurs on the microscopic level with what we have termed molecular talk. Students engage in guiding questions, consider their old and new understandings of science, and use evidence to construct new ideas during all stages of the lesson. 相似文献
8.
Srinivas Gopu Vuradi Ravi kumar Kotha Laxma Reddy Putta Venkat Reddy 《Nucleosides, nucleotides & nucleic acids》2019,38(5):349-373
A novel ligand BOPIP (BOPIP?=?{2-(4-(benzyloxy)phenyl)-1H-imidazo[4,5-f][1,10]phenanthroline}) and its mononuclear Ru(II) polypyridyl complexes [Ru(phen)2 BOPIP]2+(1) (phen?=?1,10-Phenanthrolene), [Ru(bpy)2 BOPIP]2+(2) (bpy?=?2,2′ bipyridyl), [Ru(dmb)2 BOPIP]2+(3) (dmb?=?4, 4′ -dimethyl 2, 2′ -bipyridine), [Ru(Hdpa)2 BOPIP]2+(4) (Hdpa?=?2,2′dipyridylamine) have been synthesized successfully and characterized by elemental analysis, UV-vis, IR, 1H, 13C-NMR, and ESI-MS Spectroscopy. The interaction of these complexes with CT-DNA was studied using absorption, emission techniques, viscosity measurements and molecular docking studies. The docking study also supports the binding ability of complexes obtained through the absorption and emission techniques. These studies reveal that the Four Ru(II) polypyridyl complexes bind to DNA predominantly by intercalation. The Antimicrobial activity and cytotoxicity of these complexes are also reported. 相似文献
9.
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
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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
11.
Christina W. C. Branco Betina Kozlowsky-Suzuki Susana José De Paggi 《Studies on Neotropical Fauna and Environment》2013,48(3):255-265
Abstract A four-year study of species composition of the zooplankton community was conducted at Lagoa Comprida, a Brazilian coastal lagoon. Forty-two species of rotifers were recorded and illustrated. All rotifer species, except Lecane boettgeri Koste, 1986 and Macrochaetus kostei, José de Paggi, Branco &; Kozlowsky-Suzuki, 2000, have already been found in other areas of Brazil. Some factors, which probably favored the dominant richness and density of rotifers in the zooplankton community, are discussed. 相似文献
12.
Sunil Kumar Dixit Durga Prasad Hota Parvathy Rajan Dr Prasanta Kumar K Mishra Tapas Kumar Goswami Manish Mahawar 《Preparative biochemistry & biotechnology》2017,47(2):137-142
Intraphagocytic survival of Salmonella Typhimurium (ST) depends (at least in part) upon its ability to repair oxidant-damaged macromolecules. Met residues either free or in protein bound form are highly susceptible to phagocyte-generated oxidants. Oxidation of Mets leads to Met-SO formation, consequently loss of protein functions that results in cell death. Methionine sulfoxide reductase (Msr) reductively repairs Met-SO to Met in the presence of thioredoxin (trx) and thioredoxin reductase (trxR). Earlier we reported that methionine sulfoxide reductase A (msrA) gene deletion strain of ST suffered oxidative stress.[1] Thioredoxin system of ST comprises of two thioredoxins (trxA and trxC) and one thioredoxin reductase (trxB). Preferred trx utilized in MsrA-mediated repair of Met-SO is not known. In current study, we cloned, expressed, and purified ST TrxA, TrxB, TrxC, and MsrA in recombinant forms. The migration of TrxA, TrxB, TrxC, and MsrA proteins was approximately 10, 36, 16, and 26?kDa on SDS-gels. The nicotinamide adenine dinucleotide phosphate hydrogen (NADPH)-linked reductase assays interpreted that MsrA utilized two times more NADPH for the reduction of S-methyl p-tolyl sulfoxide when TrxA was included in the assays as compared to TrxC. 相似文献
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Avinashnarayan Venkatanarayan Payal Raulji William Norton 《Cell cycle (Georgetown, Tex.)》2016,15(2):164-171
TP53 is highly mutated in human cancers, thus targeting this tumor suppressor pathway is highly desirable and will impact many cancer patients.1,2 Therapeutic strategies to reactivate the p53-pathway have been challenging,3,4 and no effective treatment exists.5 We utilized the p53-family members, p63 and p73, which are not frequently mutated in cancer, to treat p53-defective cancers. The N-terminal splice variants of p63 and p73 are denoted as the TA and ΔN isoforms. We recently demonstrated that deletion of either ΔNp63 or ΔNp73 in p53-deficient mouse tumors results in tumor regression mediated by metabolic programming. Using this strategy, we identified pramlintide, a synthetic analog of amylin, as an effective treatment for p53 deficient and mutant tumors. Here, we show the utility of using pramlintide, as a potential cancer preventive option for p53-deficient tumors in mouse models. Additionally, we found that in vivo inhibition of both ΔNp63 and ΔNp73 in combination accelerates tumor regression and increases survival of p53-deficient mice. We report that inhibition of both ΔNp63 and ΔNp73 in combination results in upregulation of 3 key metabolic regulators, IAPP, GLS2, and TIGAR resulting in an increase in apoptosis and tumor regression in ΔNp63/ΔNp73/p53 deficient thymic lymphomas. These data highlight the value of generating inhibitors that will simultaneously target ΔNp63 and ΔNp73 to treat cancer patients with alterations in p53. 相似文献
14.
Hana Popelka 《Autophagy》2017,13(3):449-451
Atg13 is an essential subunit of the Atg1 autophagy initiation complex in yeast and its mammalian counterpart, ATG13, is indispensable for autophagy induction by the ULK1 complex. The N terminus of the protein folds into a HORMA domain, an architecture that has been revealed by crystallography.1-4 In human cells, the ATG13 HORMA domain interacts directly with ATG14, a subunit of the class III phosphatidylinositol 3-kinase complex.5 In budding yeast, the HORMA domain of Atg13 recruits Atg14, but a direct interaction remains to be proven.1 The amino acid sequence that follows the HORMA domain does not adopt any 3-dimensional structure on its own; therefore, it is termed an intrinsically disordered region (IDR). Here we discuss the results of 2 recent studies in light of previous reports on Atg13 from yeast. Together, they yield an insight into the molecular mechanism for the function of this intriguing protein, and reveal why Atg13, as well as the mammalian homolog ATG13, cannot have a structurally rigid architecture. 相似文献
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Anastasia A. Lunina Mikhail A. Nikitin Aleksandra S. Shiian Alexander V. Ereskovsky Oleg A. Kovtun Alexander L. Vereshchaka 《分类学与生物多样性》2019,17(3):245-259
The genus Hemimysis (Malacostraca: Mysida: Mysidae) encompasses near-bottom, demersal and cave-dwelling mysids living in the marine, brackish and freshwater habitats around the European coast, from the Caspian Sea to the Scandinavian Peninsula. We conducted cladistic analysis of 52 morphological characters of all nine species and three subspecies of the genus Hemimysis. We also completed a molecular analysis based on three molecular markers of Hemimysis lamornae (Couch, 1856) found in the English Channel, the Mediterranean Sea, and the Black Sea. Both analyses did not support monophyly of Hemimysis lamornae. We thus consider the former subspecies H. lamornae pontica (Czerniavsky, 1882) and H. lamornae mediterranea Bacescu, 1936 as valid species. Analysis of mitochondrial cytochrome oxidase subunit I (COI) sequences of H. pontica shows no significant divergence between mysids living in the marine caves of Crimea and Bulgaria. Morphological trends in Hemimysis are discussed, H. pontica Czerniavsky, 1882 is redescribed, and a new key to all 11 species of the genus is given. 相似文献
16.
In this study, we use the measured extent of metal adsorption onto bacterial cells to constrain a linear free energy relationship that allows estimation of unknown stability constants for metal-bacterial surface complexes based on the value of corresponding aqueous metal-acetate stability constants. A previous study (Fein et al., 2001) used metal adsorption experiments to constrain a similar relationship, but the experiments were conducted using acid-washed bacteria, and subsequent evidence (Borrok et al., 2004a) shows that the acid-washing step affects the extent of adsorption of a number of metals onto bacterial surfaces. We measured the adsorption of Zn, Ni, Co, Sr, and Nd onto Bacillus subtilis in 0.1 M NaClO4 as a function of pH and metal:bacterial site ratio, using a non-electrostatic discrete four-site model of the bacterial protonation reactions as a basis for the metal adsorption modeling. The adsorption of the divalent cations (Zn, Ni, Co, and Sr) could best be modeled by considering adsorption reactions involving three sites on the bacterial surface; we used a one-site model to account for the Nd data that covered a more restricted pH range. The calculated stability constants for metal-Site 2 bacterial surface complexes are used to re-calibrate the linear free energy relationship previously defined by Fein et al. (2001). There is a significant difference between the original and the re-calibrated lines for weakly binding cations such as Sr2 +, but the difference becomes negligible for the stronger-binding cations. Because the linear free energy relationship defined in this study was calibrated from experiments that involved bacteria that were not exposed to acidic conditions, the estimated stability constant values that result from using this relationship are likely to reasonably reflect bacterial adsorption behaviors that occur in realistic geologic settings. 相似文献
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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
18.
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
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《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