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21.
Jeffrey Helgager Hart G. Lidov Navin R. Mahadevan Mark W. Kieran Keith L. Ligon Sanda Alexandrescu 《Diagnostic pathology》2017,12(1):82
Background
KIAA1549-BRAF fusion is the most common genetic event in pilocytic astrocytoma (PA), and leads to activation of the mitogen activated protein kinase (MAPK) signaling pathway. Fusions of BRAF with other partner genes, as well as other genetic alterations not involving BRAF but also leading to MAPK pathway activation have been described rarely.Case presentation
We present a new fusion partner in the low-grade glioma of a 10-year-old male, who presented with headaches and recent episodes of seizures. Magnetic resonance imaging (MRI) demonstrated a right temporal lobe tumor. Histological and immunohistochemical evaluation, and a next generation sequencing assay (Oncopanel, Illumina, 500 genes) including breaKmer analysis for chromosomal rearrangements were performed.Histology was remarkable for a low-grade glioma composed of mildly atypical astrocytes with piloid processes, in a focally microcystic background. Mitoses were not seen; unequivocal Rosenthal fibers or eosinophilic granular bodies were absent. The tumor was positive for OLIG2 and GFAP and negative for BRAF V600E and IDH1 R132H mutant protein immunostains. Oncopanel showed low SOX2 (3q26.33) copy number gain, and no gains at 7q34. There were no significant single nucleotide variants. BreaKmer detected a GIT2-BRAF fusion with loss of BRAF exons 1–8. The integrated diagnosis was low-grade glioma with piloid features, most consistent with pilocytic astrocytoma, WHO grade I.Conclusion
GIT2-BRAF fusion has not been reported in the literature in any tumor. Given that the BRAF sequence deleted is identical to that seen in other fusion events in PA, it most likely acts as tumor driver by activation of the MAPK pathway.22.
Semen-derived enhancer of virus infection (SEVI), a naturally occurring peptide fragment of prostatic acid phosphatase, enhances HIV infectivity by forming cationic amyloid fibrils that aid the fusion of negatively charged virion and target cell membranes. Cu(II) and Zn(II) inhibit fibrillization of SEVI in a kinetic assay using the fibril-specific dye ThT. TEM suggests that the metals do not affect fibril morphology. NMR shows that the metals bind to histidines 3 and 23 in the SEVI sequence. ITC experiments indicate that SEVI forms oligomeric complexes with the metals. Dissociation constants are micromolar for Cu(II) and millimolar for Zn(II). Because the Cu(II) and Zn(II) concentrations that inhibit fibrillization are comparable with those found in seminal fluid the metals may modulate SEVI fibrillization under physiological conditions. 相似文献
23.
土典霉金色变种AT8951菊粉酶粗酶液经硫酸铵分段沉淀、DEAE Cellulose DE32离子交换、超滤、Sephadex G-150凝胶过滤和FPLC,获得两个菊粉酶组分EⅠ和EⅡ,经分析型FPLG和PAGE鉴定为单一纯和分析纯。EⅠ分子量为66KD,最适作用温度和pH分别55℃和5.8;EⅡ分子量为56KD,最适作用温度为57℃,最适pH为6.0。EⅠ和EⅡ皆为糖蛋白,多糖含量分别为24.7%和22%,都属于内切酶。本文还对EⅠ和EⅡ的Km值和I/s值,温度、pH、离子对酶活作用的影响等进行了研究。 相似文献
24.
Relationships in the Drosophila obscura species group, inferred from mitochondrial cytochrome oxidase II sequences 总被引:2,自引:0,他引:2
We compare the sequences for the mitochondrial cytochrome oxidase II gene
of 13 species of the Drosophila obscura group. The survey includes six
members of the D. affinis subgroup, four of the D. pseudoobscura subgroup,
and three of the D. obscura subgroup. In all species, the gene is 688
nucleotides in length, encoding a protein of 229 amino acids plus the first
position T of the stop codon. The sequences show the typical
high-transition bias for closely related species, but that bias is
essentially eliminated for species pairs of > 5% sequence divergence.
The phylogenetic relationships in the species group are inferred using both
neighbor-joining and maximum parsimony. The two procedures give comparable
results, showing that the D. affinis and D. pseudoobscura subgroups are
monophyletic groupings that appear to have closer affinities to one another
than either has to the D. obscura subgroup. We use transversion distances
to estimate times of divergence, on the basis of three different estimates
of the time of separation of the D. obscura species group from the D.
melanogaster group. If that event occurred 35 Mya, then we can estimate the
origin of the nearctic forms at approximately 22 Mya and the separation of
the D. affinis and D. pseudoobscura subgroups at approximately 17 Mya.
相似文献
25.
A. T. Alexandrescu S. A. Dames R. Wiltscheck 《Protein science : a publication of the Protein Society》1996,5(9):1942-1946
Hydrogen-exchange rates for an OB-fold subdomain fragment of staphylococcal nuclease have been measured at pH 4.7 and 4 degrees C, conditions close to the minimum of acid/base catalyzed exchange. The strongest protection from solvent exchange is observed for residues from a five-stranded beta-barrel in the NMR structure of the protein. Protection factors, calculated from the experimental hydrogen-exchange rates, range between 1 and 190. Similarly small protection factors have in many cases been attributed to "molten globule" conformations that are supposed to lack a specific tertiary structure. The present results suggest that marginal protection from solvent exchange does not exclude well-defined structure. 相似文献
26.
A T Alexandrescu R W Broadhurst C Wormald C L Chyan J Baum C M Dobson 《European journal of biochemistry》1992,210(3):699-709
1H-NMR assignments have been defined for the aromatic-ring protons of the bovine, guinea pig and human variants of alpha-lactalbumin. Spin-system networks were identified by means of double-quantum-filtered two-dimensional J-correlated spectroscopy and two-dimensional relayed coherence spectroscopy data. Analysis of two-dimensional nuclear-Overhauser-enhancement spectroscopy data of the proteins indicated that in each case two clusters of aromatic residues exist. The two clusters are also evident in the crystal structure of the human protein, and this evidence, in conjunction with sequence differences between the three proteins, permitted sequence-specific assignments to be made for the majority of aromatic residues. Remaining ambiguities in the assignments could be resolved by analysis of photochemically induced dynamic nuclear polarization (PCIDNP) effects. Comparison of the PCIDNP spectra of the three proteins indicated the presence of only minor differences in the surface exposure of conserved aromatic residues. Taken together, these results indicate that the environments of the conserved aromatic residues in bovine, guinea pig and human alpha-lactalbumin in solution are very similar to each other, and that the solution and the crystal forms of at least the human protein are similar. 相似文献
27.
Coupling between local structure and global stability of a protein: mutants of staphylococcal nuclease 总被引:9,自引:0,他引:9
Staphylococcal nuclease exists in solution as a mixture of two folded (N and N') and two unfolded (U and U*) forms. Earlier workers [Evans et al. (1989) Biochemistry 28, 362] have proposed that the N'/N and U/U* structural differences involve cis/trans isomerization about the Lys116-Pro117 peptide bond with N and U cis and N' and U* trans. The present results show that residue changes throughout the nuclease structure have large effects on the distribution of the N and N'forms. The N'/N ratios at 313 K for nuclease H124L (N'/N = 0.07) and nuclease G79S (N'/N = 12) differ by 2 orders of magnitude. Thermodynamic parameters for equilibria linking the two folded and two unfolded substates were evaluated for seven mutants of nuclease which were found by kinetic assays to have similar enzymatic activities but by NMR spectroscopy to have a wide dispersion of thermal stabilities. Our results indicate that mutational perturbations of the N'/N equilibrium in folded nuclease (delta G for the N in equilibrium N' reaction) are strongly coupled to changes in the stability of the N form (delta G for the N in equilibrium U reaction), but much less so to the stability of the N' form (delta G for the N' in equilibrium U* reaction). 相似文献
28.
Sean R Landman Tae Hyun Hwang Kevin AT Silverstein Yingming Li Scott M Dehm Michael Steinbach Vipin Kumar 《BMC genomics》2014,15(1)
Background
Personal genome assembly is a critical process when studying tumor genomes and other highly divergent sequences. The accuracy of downstream analyses, such as RNA-seq and ChIP-seq, can be greatly enhanced by using personal genomic sequences rather than standard references. Unfortunately, reads sequenced from these types of samples often have a heterogeneous mix of various subpopulations with different variants, making assembly extremely difficult using existing assembly tools. To address these challenges, we developed SHEAR (Sample Heterogeneity Estimation and Assembly by Reference; http://vk.cs.umn.edu/SHEAR), a tool that predicts SVs, accounts for heterogeneous variants by estimating their representative percentages, and generates personal genomic sequences to be used for downstream analysis.Results
By making use of structural variant detection algorithms, SHEAR offers improved performance in the form of a stronger ability to handle difficult structural variant types and better computational efficiency. We compare against the lead competing approach using a variety of simulated scenarios as well as real tumor cell line data with known heterogeneous variants. SHEAR is shown to successfully estimate heterogeneity percentages in both cases, and demonstrates an improved efficiency and better ability to handle tandem duplications.Conclusion
SHEAR allows for accurate and efficient SV detection and personal genomic sequence generation. It is also able to account for heterogeneous sequencing samples, such as from tumor tissue, by estimating the subpopulation percentage for each heterogeneous variant.Electronic supplementary material
The online version of this article (doi:10.1186/1471-2164-15-84) contains supplementary material, which is available to authorized users. 相似文献29.
Oprişan G Coste H Lupulescu E Oprişoreanu AM Szmal C Onita I Popovici N Ionescu LE Bicheru S Enache N Ceianu C Czobor F Olaru E Alexandrescu V Radu DL Onu A Popa MI 《Roumanian archives of microbiology and immunology》2006,65(3-4):79-82
Since the events of avian influenza (AI) caused by H5N1 subtype from Hong Kong (1997), the people worldwide have been confronted with new waves of epizootic influenza. In 2005 in Romania an unprecedent H5N1 epizootic occurred in domestic and wild birds. Therefore an immediate investigation by molecular approach of this highly pathogenic H5N1 strain was necessary. The virus isolation and the RNA extraction were performed in the Institute of Diagnosis and Animal Health while PCR and sequencing were carried out in Cantacuzino Institute. Herein we report the first evidence of H5N1 presence in Romanian fowls. The phylogenetic analysis of haemagglutinin and neuraminidase gene indicated a close relationship of Romanian strains to those from Siberia and China. The virological and molecular analysis of the first strains of avian virus from Romania confirmed the presence of H5N1 subtype, belonging to the genetic line Z. These results indicate that the avian virus from this genetic line is directly derived from the highly pathogenic viruses isolated in China and Russia in 2005. 相似文献
30.
Tecu C Genetay E Alexandrescu V Vabret A Freymuth F 《Roumanian archives of microbiology and immunology》2006,65(3-4):83-86
The aim of the study was to determine the etiology of the viral bronchiolites in children by using direct immunofluorescence test and 3 RT-PCR Multiplex (S.Bellau-Pujol) The study was performed on 122 nasal inspirations collected from 3 weeks-6 month old children hospitalizated in the pediatrics service of CH Rouen. The results were that the majority (53%) of bronchiolites in children had like etiology RSV and a lot of these infections had double viral etiology (26% RSV+ Rhinovirus; 2,7% RSV+HMPV and 1% RSV+Coronavirus 229E). An important viral factor which gives bronchiolitis in children is HMPV (11%). We also find respiratory infections with triple viral etiology: RSV+Influenza A virus + Rhinovirus. 相似文献