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101.
NsPEF ablation induces apoptosis markers, but specific cell death pathways have not been fully defined. To identify nsPEF-activated cell death pathways, wildtype human Jurkat cells and clones with deficiencies in extrinsic and intrinsic apoptosis pathways were investigated. NsPEFs activated caspase isozymes and induced identical electric field-dependent cell death in clones deficient in FADD or caspase-8, indicating that extrinsic apoptosis pathways were not activated. This was confirmed when cytochrome c release was shown to be unaffected by the pan caspase inhibitor, z-VAD-fmk. NsPEF-treated APAF-1-silenced cells did not exhibit caspase-3/7 and -9 activities and corresponding electric field-dependent cell death in this clone was attenuated compared to its vector control at low, but not at high electric fields. These data demonstrate that nsPEFs induce intrinsic apoptosis activate by cytochrome c release from mitochondria through an APAF-1- and caspase-dependent pathway as well as through caspase-independent mechanisms that remain to be defined. Furthermore, the results establish that nsPEFs can overcome natural and oncogenic mechanisms that promote cell survival through inhibition of apoptosis and other cell death mechanisms. 相似文献
102.
Zhang J Blackmore PF Hargrave BY Xiao S Beebe SJ Schoenbach KH 《Archives of biochemistry and biophysics》2008,471(2):240-248
Nanosecond pulse stimulation of a variety of cells produces a wide range of physiological responses (e.g., apoptosis, stimulation of calcium (Ca2+) fluxes, changes in membrane potential). In this study, we investigated the effect of nanosecond pulses, which generate intense electric fields (nsPEFs), on human platelet aggregation, intracellular free Ca2+ ion concentration ([Ca2+]i) and platelet-derived growth factor release. When platelet rich plasma was pulsed with one 300 ns pulse with an electric field of 30 kV/cm, platelets aggregated and a platelet gel was produced. Platelet aggregation was observed with pulses as low as 7 kV/cm with maximum effects seen with approximately 30 kV/cm. The increases in intracellular Ca2+ release and Ca2+ influx were dose dependent on the electrical energy density and were maximally stimulated with approximately 30 kV/cm. The increases in [Ca2+]i induced by nsPEF were similar to those seen with thapsigargin but not thrombin. We postulate that nsPEF caused Ca2+ to leak out of intracellular Ca2+ stores by a process involving the formation of nanopores in organelle membranes and also caused Ca2+ influx through plasma membrane nanopores. We conclude that nsPEFs dose-dependently cause platelets to rapidly aggregate, like other platelet agonists, and this is most likely initiated by the nsPEFs increasing [Ca2+]i, however by a different mechanism. 相似文献
103.
Surendra Kumar ?smund Skj?veland Russell JS Orr P?l Enger Torgeir Ruden Bj?rn-Helge Mevik Fabien Burki Andreas Botnen Kamran Shalchian-Tabrizi 《BMC bioinformatics》2009,10(1):357
Background
Large multigene sequence alignments have over recent years been increasingly employed for phylogenomic reconstruction of the eukaryote tree of life. Such supermatrices of sequence data are preferred over single gene alignments as they contain vastly more information about ancient sequence characteristics, and are thus more suitable for resolving deeply diverging relationships. However, as alignments are expanded, increasingly numbers of sites with misleading phylogenetic information are also added. Therefore, a major goal in phylogenomic analyses is to maximize the ratio of information to noise; this can be achieved by the reduction of fast evolving sites. 相似文献104.
Gallegos Ruiz MI Floor K Roepman P Rodriguez JA Meijer GA Mooi WJ Jassem E Niklinski J Muley T van Zandwijk N Smit EF Beebe K Neckers L Ylstra B Giaccone G 《PloS one》2008,3(3):e0001722
Background
Lung cancer causes approximately 1.2 million deaths per year worldwide, and non-small cell lung cancer (NSCLC) represents 85% of all lung cancers. Understanding the molecular events in non-small cell lung cancer (NSCLC) is essential to improve early diagnosis and treatment for this disease.Methodology and Principal Findings
In an attempt to identify novel NSCLC related genes, we performed a genome-wide screening of chromosomal copy number changes affecting gene expression using microarray based comparative genomic hybridization and gene expression arrays on 32 radically resected tumor samples from stage I and II NSCLC patients. An integrative analysis tool was applied to determine whether chromosomal copy number affects gene expression. We identified a deletion on 14q32.2-33 as a common alteration in NSCLC (44%), which significantly influenced gene expression for HSP90, residing on 14q32. This deletion was correlated with better overall survival (P = 0.008), survival was also longer in patients whose tumors had low expression levels of HSP90. We extended the analysis to three independent validation sets of NSCLC patients, and confirmed low HSP90 expression to be related with longer overall survival (P = 0.003, P = 0.07 and P = 0.04). Furthermore, in vitro treatment with an HSP90 inhibitor had potent antiproliferative activity in NSCLC cell lines.Conclusions
We suggest that targeting HSP90 will have clinical impact for NSCLC patients. 相似文献105.
OLF Weyl MK Schirrmann JS Hargrove T Bodill ER Swartz 《African Journal of Aquatic Science》2017,42(4):359-365
Largemouth bass Micropterus salmoides are a popular North American angling species that was introduced into South Africa in 1928. To enhance the largemouth bass fisheries, Florida bass Micropterus floridanus were introduced into KwaZulu Natal, South Africa, in 1980. Knowledge on the status of M. floridanus in South Africa is required, because it lives longer and reaches larger sizes than M. salmoides, which may result in heightened impacts on native biota. Because M. floridanus are morphologically similar, but genetically distinct from M. salmoides, the distribution of this species was assessed by genetically screening 185 Micropterus sp. individuals sampled from 20 localities across South Africa using the mitochondrial ND2 gene. Individuals with mitochondrial DNA matching M. salmoides were recovered from 16 localities, whereas M. floridanus mitochondrial DNA was recovered from 13 localities. At nine localities (45%), the mitochondrial DNA of both species was detected. These results demonstrate M. floridanus dispersal to multiple sites across South Africa. 相似文献
106.
D C Beebe C H Latker H A Jebens M C Johnson D E Feagans R N Feinberg 《Developmental biology》1986,114(2):361-368
The nature and origin of the proteins of the vitreous humor were examined in chickens during embryonic and early posthatching stages. The major proteins of the vitreous humor were similar in electrophoretic mobility to plasma proteins at all ages examined. Earlier studies from our laboratory and experiments described below showed that plasma proteins continuously entered and left the eye throughout its development. From these data it was concluded that the majority of vitreous-humor proteins were derived from the blood. The protein concentration of the vitreous humor was 13% of that of the plasma from embryonic Days 6 through 15 (E6 through E15). After E15, the relative protein concentration in the vitreous humor declined with respect to the plasma and reached 4% of the plasma protein concentration at hatching. Several possibilities were considered to account for how proteins can rapidly enter and leave the eye, yet maintain a steady-state concentration in the vitreous humor that is less than one-seventh of that in the blood. 相似文献
107.
Explants of the central region of lens epithelia from early chicken embryos differentiate in vitro to form lens fiber cells when cultured in the presence of chicken vitreous humor. Hybridization of a 32P-labeled v-myc viral oncogene DNA probe to RNA extracted from differentiating explants and immobilized on nitrocellulose filters indicates that levels of 2.5 kb c-myc mRNA are transiently elevated 5-10-fold in the differentiating cells. Increased levels of c-myc mRNA are observed within 30 min of the initiation of differentiation in vitro and persist for 8-9 h. Thymidine labeling of nuclei in differentiating explants indicates that entry of cells into S phase is inhibited during this period, as differentiating cells complete a final round of mitosis and withdraw from the cell cycle. Levels of c-myc mRNA are also elevated in the peripheral region of the lens epithelium, which contains cells undergoing differentiation in vivo, suggesting that the regulation of c-myc mRNA which occurs in vitro may also occur in vivo. c-myc mRNA, c-fos mRNA, and c-src mRNA showed distinct patterns of regulation associated with lens fiber formation in vivo, thus providing evidence that the regulation of c-myc mRNA is specific to this proto-oncogene. The finding that c-myc mRNA undergoes a specific, transient elevation in differentiating lens cells as they withdraw from the cell cycle contrasts with a large body of evidence linking enhanced c-myc expression with increased cell proliferation. 相似文献
108.
A characteristic feature of the sperm P1 protamines of eutherian mammals is
the constant presence of six to nine cysteine residues per molecule. During
spermiogenesis these residues become oxidized to form a three-dimensional
network of disulfide bridges between, and within, protamine molecules in
the sperm chromatin. This covalent cross linking strongly stabilizes
eutherian sperm nuclei. In contrast, protamines sequenced from teleost
fish, birds, monotremes, and marsupials all lack cysteine residues and
their sperm nuclei, without the stabilizing cross links, are easily
decondensed in vitro. We have now found that one genus of tiny, shrewlike
dasyurid marsupials, the Planigales, possess P1 protamines containing five
to six cysteine residues. These residues appear to have evolved since the
divergence of Planigales from other members of the family Dasyuridae, such
as the marsupial mouse, Sminthopsis crassicaudata. We believe this
constitutes a case of convergent evolution in a subfamily of dasyurid
marsupials toward the cysteine-rich eutherian form of sperm protamine P1.
相似文献
109.
Evidence for independent recruitment of zeta-crystallin/quinone reductase (CRYZ) as a crystallin in camelids and hystricomorph rodents 总被引:3,自引:2,他引:1
Zeta-crystallin/quinone reductase (CRYZ) is an NADPH oxidoreductase
expressed at very high levels in the lenses of two groups of mammals:
camelids and some hystricomorph rodents. It is also expressed at very low
levels in all other species tested. Comparative analysis of the mechanisms
mediating the high expression of this enzyme/crystallin in the lens of the
Ilama (Lama guanacoe) and the guinea pig (Cavia porcellus) provided
evidence for independent recruitment of this enzyme as a lens crystallin in
both species and allowed us to elucidate for the first time the mechanism
of lens recruitment of an enzyme- crystallin. The data presented here show
that in both species such recruitment most likely occurred through the
generation of new lens promoters from nonfunctional intron sequences by the
accumulation of point mutations and/or small deletions and insertions.
These results further support the idea that recruitment of CRYZ resulted
from an adaptive process in which the high expression of CRYZ in the lens
provides some selective advantage rather than from a purely neutral
evolutionary process.
相似文献
110.
Neutralization of influenza virus by normal human sera: mechanisms involving antibody and complement 总被引:3,自引:0,他引:3
D P Beebe R D Schreiber N R Cooper 《Journal of immunology (Baltimore, Md. : 1950)》1983,130(3):1317-1322
All normal human sera examined neutralized WS/33 H1N1 influenza virus efficiently by one of two antibody-dependent mechanisms. A minority of the sera contained moderate levels of IgG antibody directed against the viral hemagglutinin that had the ability to directly neutralize the virus. The majority of sera tested contained very low levels of IgG anti-hemagglutinin antibody, which was detectable with a specific ELISA but not by conventional HAI assays. Such IgG antibody was unable to directly neutralize the virus. Studies with agammaglobulinemic serum and with sera depleted of and reconstituted with complement components established essential roles for IgG and the components of the classical complement pathway through C3 for neutralization. The components of the alternative and membrane attack pathways were not needed for neutralization. As anticipated from the requirement for IgG and exclusive mediation of neutralization by the classical pathway, the virus-IgG immune complex activated purified C1. Binding of C3 and C4 to the virus was demonstrated, as was classical pathway-mediated triggering of the alternative pathway, with recruitment of properdin. In addition, the H1N1 influenza virus also directly activated the alternative complement pathway in human serum, leading to C3 and properdin deposition on the viral envelope. Such direct alternative pathway activation also required immunoglobulin. However, the alternative pathway alone was unable to neutralize the virus. Thus, most normal sera examined contain low levels of IgG anti-hemagglutinin antibody, which activate the classical pathway of the complement system and neutralize WS/33 influenza virus by deposition of C3 and C4 on the viral envelope. 相似文献