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81.
Astroglial Phosphoinositide Hydrolysis During Combined Glucose-Oxygen Deprivation: Role of the Metabotropic Glutamate Receptor 总被引:2,自引:2,他引:0
†Joseph E. Segeleon †Diane C. Lipscomb † Steven E. Haun Victoria L. Trapp ‡Lloyd A. Horrocks 《Journal of neurochemistry》1995,65(3):1115-1123
Abstract: Phosphatidylinositol bisphosphate hydrolysis, leading to the production of myo -inositol trisphosphate and diacylglycerol, may play a significant role in the pathogenesis of hypoxic-ischemic brain injury. We used tritiated myo -inositol phosphate (3 H-IP) accumulation as a means to quantitate phosphoinositide hydrolysis in prelabeled astroglial cultures subjected to combined glucose-oxygen deprivation. Astroglial cultures exposed to combined glucose-oxygen deprivation had significantly greater 3 H-IP accumulation compared with cultures exposed to control conditions. To delineate the role of the metabotropic glutamate receptor in astroglial phosphoinositide hydrolysis during combined glucose-oxygen deprivation, we studied the effects of two metabotropic glutamate receptor antagonists, 2-amino-3-phosphonopropionic acid and (+)-methyl-4-carboxyphenylglycine. 2-Amino-3-phosphonopropionic acid attenuated the accumulation of 3 H-IP during combined glucose-oxygen deprivation but acted as an agonist under control conditions. (+)-Methyl-4-carboxyphenylglycine had no effect on 3 H-IP accumulation during combined glucose-oxygen deprivation or under control conditions. These results suggest that activation of astroglial phosphoinositide hydrolysis during combined glucose-oxygen deprivation may be mediated, at least in part, by the metabotropic glutamate receptor. 相似文献
82.
83.
Improving cold storage and processing traits in potato through targeted gene knockout 总被引:3,自引:0,他引:3
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Benjamin M. Clasen Thomas J. Stoddard Song Luo Zachary L. Demorest Jin Li Frederic Cedrone Redeat Tibebu Shawn Davison Erin E. Ray Aurelie Daulhac Andrew Coffman Ann Yabandith Adam Retterath William Haun Nicholas J. Baltes Luc Mathis Daniel F. Voytas Feng Zhang 《Plant biotechnology journal》2016,14(1):169-176
84.
The Olifants River, a tributary of the Limpopo River system, is one of the most polluted rivers in South Africa. In May 2011 the concentrations of metals in fish muscle tissue from two impoundments, Loskop and Flag Boshielo dams, on the Olifants River were measured and a human health risk assessment conducted to investigate whether it was safe to consume Labeo rosae from these impoundments. Labeo rosae is one of the most common pan fish in these impoundments and is readily available to rural communities. Metals are accumulating in the muscle tissue of L. rosae even although the fish populations appear to be healthy. At Loskop Dam all L. rosae analysed exceeded the recommended hazard quotient (HQ) of 1 for antimony, and less than 50% exceeded that for lead. At Flag Boshielo Dam, the recommended HQ was exceeded for lead in less than 50% of L. rosae analysed, and more than 50% exceeded that for antimony. The weekly consumption of 150?g of L. rosae muscle tissue from these impoundments may pose an unacceptable health risk to rural communities. 相似文献
85.
M L Bermingham S C Bishop J A Woolliams R Pong-Wong A R Allen S H McBride J J Ryder D M Wright R A Skuce S WJ McDowell E J Glass 《Heredity》2014,112(5):543-551
Tuberculosis (TB) caused by Mycobacterium bovis is a re-emerging disease of
livestock that is of major economic importance worldwide, as well as being a zoonotic
risk. There is significant heritability for host resistance to bovine TB (bTB) in dairy
cattle. To identify resistance loci for bTB, we undertook a genome-wide association study
in female Holstein–Friesian cattle with 592 cases and 559 age-matched controls from
case herds. Cases and controls were categorised into distinct phenotypes: skin test and
lesion positive vs skin test negative on multiple occasions, respectively. These animals
were genotyped with the Illumina BovineHD 700K BeadChip. Genome-wide rapid association
using linear and logistic mixed models and regression (GRAMMAR), regional heritability
mapping (RHM) and haplotype-sharing analysis identified two novel resistance loci that
attained chromosome-wise significance, protein tyrosine phosphatase receptor T
(PTPRT; P=4.8 × 10−7) and myosin
IIIB (MYO3B; P=5.4 × 10−6). We estimated
that 21% of the phenotypic variance in TB resistance could be explained by all of
the informative single-nucleotide polymorphisms, of which the region encompassing the
PTPRT gene accounted for 6.2% of the variance and a further 3.6%
was associated with a putative copy number variant in MYO3B. The results from
this study add to our understanding of variation in host control of infection and suggest
that genetic marker-based selection for resistance to bTB has the potential to make a
significant contribution to bTB control. 相似文献
86.
Improved soybean oil quality by targeted mutagenesis of the fatty acid desaturase 2 gene family 总被引:2,自引:0,他引:2
87.
Edward WJ Curry 《BMC bioinformatics》2014,15(1)
Background
A generalized notion of biclustering involves the identification of patterns across subspaces within a data matrix. This approach is particularly well-suited to analysis of heterogeneous molecular biology datasets, such as those collected from populations of cancer patients. Different definitions of biclusters will offer different opportunities to discover information from datasets, making it pertinent to tailor the desired patterns to the intended application. This paper introduces ‘GABi’, a customizable framework for subspace pattern mining suited to large heterogeneous datasets. Most existing biclustering algorithms discover biclusters of only a few distinct structures. However, by enabling definition of arbitrary bicluster models, the GABi framework enables the application of biclustering to tasks for which no existing algorithm could be used.Results
First, a series of artificial datasets were constructed to represent three clearly distinct scenarios for applying biclustering. With a bicluster model created for each distinct scenario, GABi is shown to recover the correct solutions more effectively than a panel of alternative approaches, where the bicluster model may not reflect the structure of the desired solution. Secondly, the GABi framework is used to integrate clinical outcome data with an ovarian cancer DNA methylation dataset, leading to the discovery that widespread dysregulation of DNA methylation associates with poor patient prognosis, a result that has not previously been reported. This illustrates a further benefit of the flexible bicluster definition of GABi, which is that it enables incorporation of multiple sources of data, with each data source treated in a specific manner, leading to a means of intelligent integrated subspace pattern mining across multiple datasets.Conclusions
The GABi framework enables discovery of biologically relevant patterns of any specified structure from large collections of genomic data. An R implementation of the GABi framework is available through CRAN (http://cran.r-project.org/web/packages/GABi/index.html).Electronic supplementary material
The online version of this article (doi:10.1186/s12859-014-0355-5) contains supplementary material, which is available to authorized users. 相似文献88.
Lu Sun Shirley Haun Richard C. Jones Ricky D. Edmondson Khaled Machaca 《The Journal of biological chemistry》2009,284(30):20184-20196
Fertilization induces a species-specific Ca2+ transient with specialized spatial and temporal dynamics, which are essential to temporally encode egg activation events such as the block to polyspermy and resumption of meiosis. Eggs acquire the competence to produce the fertilization-specific Ca2+ transient during oocyte maturation, which encompasses dramatic potentiation of inositol 1,4,5-trisphosphate (IP3)-dependent Ca2+ release. Here we show that increased IP3 receptor (IP3R) sensitivity is initiated at the germinal vesicle breakdown stage of maturation, which correlates with maturation promoting factor (MPF) activation. Extensive phosphopeptide mapping of the IP3R resulted in ∼70% coverage and identified three residues, Thr-931, Thr-1136, and Ser-114, which are specifically phos pho ryl a ted during maturation. Phospho-specific antibody analyses show that Thr-1136 phos pho ryl a tion requires MPF activation. Activation of either MPF or the mitogen-activated protein kinase cascade independently, functionally sensitizes IP3-dependent Ca2+ release. Collectively, these data argue that the kinase cascades driving meiotic maturation potentiates IP3-dependent Ca2+ release, possibly trough direct phos pho ryl a tion of the IP3R.Egg activation refers to the cellular and molecular events that take place immediately following fertilization, transitioning the zygote into embryogenesis. In vertebrates, egg activation encompasses the block to polyspermy and the completion of oocyte meiosis, which is coupled to the extrusion of the second polar body. Interestingly, in all sexually reproducing organisms tested to date the cellular events associated with egg activation are Ca2+-dependent (1). Importantly the Ca2+ signal at fertilization encodes the progression of these cellular events in a defined temporal sequence that ensures a functional egg-to-embryo transition (2, 3). The first order of business for the fertilized egg is to block polyspermy, which could be lethal to the embryo. This presents a particularly difficult problem for the large Xenopus oocyte. Therefore, this species employs a fast and slow blocks to polyspermy, both of which are Ca2+-dependent (4). In addition, the Ca2+ release wave at fertilization releases the metaphase II cytostatic factor-dependent arrest in Xenopus oocytes. As is the case in other vertebrates, Xenopus eggs arrest at metaphase of meiosis II, an event that marks the completion of maturation.Therefore, Ca2+ dynamics at fertilization initiate and temporally encode critical cellular events for the egg-to-embryo transition. Specificity in Ca2+ signaling is encoded to a large extent in the spatial, temporal, and amplitude features of the Ca2+ signal. This endows Ca2+ signaling with its versatility and specificity, where in the same cell Ca2+ signals can mediate distinct cellular responses (5, 6).Ca2+ signaling pathways and intracellular organelles remodel during oocyte maturation, a complex cellular differentiation that prepares the egg for fertilization and egg activation (7, 8). In Xenopus the activity and distribution of multiple essential Ca2+-transporting proteins is modulated dramatically during oocyte maturation (8). Functional studies and mathematical modeling support the conclusion that the two critical determinants of Ca2+ signaling remodeling during Xenopus oocyte maturation are the internalization of the plasma-membrane Ca2+-ATPase, and the sensitization of inositol 1,4,5-trisphosphate (IP3)2-dependent Ca2+ release (9–11). Indeed Ca2+ release from intracellular stores through the IP3 receptor (IP3R) represents the primary source for the initial Ca2+ rise at fertilization in vertebrates (12–14). The sensitivity of IP3-dependent Ca2+ release is enhanced during maturation (10, 15). The IP3R physically clusters during maturation (9, 16), and this is associated with functional clustering of elementary Ca2+ release events (10). IP3R clustering is important for the slow and continuous nature of Ca2+ wave propagation in Xenopus eggs (10). In fact the potentiation of IP3-dependent Ca2+ release is a hallmark of Ca2+ signaling differentiation during oocyte maturation in several vertebrate and invertebrate species (17–19). However, the mechanisms underlying enhanced IP3-dependent Ca2+ release are not well understood.An attractive mechanism to explain increased IP3R sensitivity during oocyte maturation is phosphorylation, given the critical role kinase cascades play in the initiation and progression of the meiotic cell cycle. Furthermore, the affinity of the IP3R increases during mitosis apparently due to direct phosphorylation by maturation-promoting factor (MPF) (20, 21). In contrast, in starfish eggs, although the increase in Ca2+ release was dependent on MPF activation, MPF does not directly phosphorylate the IP3R, but rather it appears to mediate its effect through the actin cytoskeleton (22, 23). More recently, the MAPK cascade has been shown to be important for shaping Ca2+ dynamics in mouse eggs (24). Together, these results argue that phosphorylation plays an important role in the sensitization of IP3-dependent Ca2+ release during M-phase.Xenopus oocyte maturation is initiated by steroids that appear to act on a cell surface receptor (25). An important kinase cascade activated during maturation is the MAPK cascade that is initiated through the accumulation of Mos (Fig. 1A). This cascade culminates in the inhibition of Myt1, which phosphorylates and inhibits MPF. MPF is the key regulator of entry into M-phase and is composed of a Ser/Thr kinase subunit (cdk1) and cyclin B as a regulatory subunit. In addition, activation of Cdc25C is essential for oocyte maturation, because it represents the rate-limiting step in MPF activation (26). Cdc25C is phosphorylated by polo-like kinase through unknown upstream steps. In this work we analyze the functional regulation and phosphorylation pattern of the IP3R during oocyte maturation to better understand the role of cell cycle kinases in modulating IP3-dependent Ca2+ release.Open in a separate windowFIGURE 1.IP3-dependent Ca2+ release dynamics during maturation. A, kinase cascades driving Xenopus oocyte maturation. B, oocytes were injected with caged-IP3 and Oregan Green 1,2-bis(2-aminophenoxy)ethane-N,N,N′,N′-tetraacetic acid tetrakis 1 before imaging. Maturation was induced with progesterone, and cells were collected at different time points as indicated. Cells were imaged in line scan mode on a Zeiss LSM510 with the near UV 450 nm laser continuously on, at low intensity to produce a slow gradual IP3 rise. After imaging each cell was lysed and analyzed individually for the activation state of MAPK and MPF. MPF was assayed using an anti-phospho-Tyr-15-cdk1 antibody (arrow). Dephosphorylation is indicative of MPF activation. MAPK activation was detected using a phospho-specific MAPK antibody (arrowhead). Tubulin was the loading control (dash). C, percent of cells at each time point that either exhibit no release for the duration of the line scan (No Rel., black), puffs only (puffs, green), puffs followed by a wave (Puff-Wave, blue), or only a Ca2+ wave (Wave, red). For each time point n = 11–23 cells. D, amplitude of the first peak during the line scan as compared with the maximal Ca2+ signal. Mean ± S.E. (n = 9–18). E, latency until the first Ca2+ signal (Time to first peak) as compared with the time required to reach maximal signal (Time to Max). Mean ± S.E. (n = 9–18). For C–E: oocytes (Ooc); cells treated with progesterone that have not undergone GVBD at 2 or more hours after progesterone (p > 2); cells at GVBD and up to 0.5 h after GVBD (GVBD 0–0.5); cells from 0.5 to 2.5 h after GVBD (GVBD 0.5–2.5); fully mature eggs at 3 or more hours after GVBD (>3 egg). 相似文献
89.
Mohamed M Thabet Thomas WJ Huizinga Désirée M van der Heijde Annette HM van der Helm-van Mil 《Arthritis research & therapy》2009,11(5):1-9
Introduction
Evidence suggests that citrullinated fibrin(ogen) may be a potential in vivo target of anticitrullinated protein/peptide antibodies (ACPA) in rheumatoid arthritis (RA). We compared the diagnostic yield of three enzyme-linked immunosorbent assay (ELISA) tests by using chimeric fibrin/filaggrin citrullinated synthetic peptides (CFFCP1, CFFCP2, CFFCP3) with a commercial CCP2-based test in RA and analyzed their prognostic values in early RA.Methods
Samples from 307 blood donors and patients with RA (322), psoriatic arthritis (133), systemic lupus erythematosus (119), and hepatitis C infection (84) were assayed by using CFFCP- and CCP2-based tests. Autoantibodies also were analyzed at baseline and during a 2-year follow-up in 98 early RA patients to determine their prognostic value.Results
With cutoffs giving 98% specificity for RA versus blood donors, the sensitivity was 72.1% for CFFCP1, 78.0% for CFFCP2, 71.4% for CFFCP3, and 73.9% for CCP2, with positive predictive values greater than 97% in all cases. CFFCP sensitivity in RA increased to 80.4% without losing specificity when positivity was considered as any positive anti-CFFCP status. Specificity of the three CFFCP tests versus other rheumatic populations was high (> 90%) and similar to those for the CCP2. In early RA, CFFCP1 best identified patients with a poor radiographic outcome. Radiographic progression was faster in the small subgroup of CCP2-negative and CFFCP1-positive patients than in those negative for both autoantibodies. CFFCP antibodies decreased after 1 year, but without any correlation with changes in disease activity.Conclusions
CFFCP-based assays are highly sensitive and specific for RA. Early RA patients with anti-CFFCP1 antibodies, including CCP2-negative patients, show greater radiographic progression. 相似文献90.
Global concerns about climate changes and their association with the use of fossil fuels have accelerated research on biological
fuel production. Biological hydrogen production from hemicellulose-containing waste is considered one of the promising avenues.
A major economical issue for such a process, however, is the low substrate conversion efficiency. Interestingly, the extreme
thermophilic bacterium Caldicellulosiruptor saccharolyticus can produce hydrogen from carbohydrate-rich substrates at yields close to the theoretical maximum of the dark fermentation
process (i.e., 4 mol H2/mol hexose). The organism is able to ferment an array of mono-, di- and polysaccharides, and is relatively tolerant to high
partial hydrogen pressures, making it a promising candidate for exploitation in a biohydrogen process. The behaviour of this
Gram-positive bacterium bears all hallmarks of being adapted to an environment sparse in free sugars, which is further reflected
in its low volumetric hydrogen productivity and low osmotolerance. These two properties need to be improved by at least a
factor of 10 and 5, respectively, for a cost-effective industrial process. In this review, the physiological characteristics
of C. saccharolyticus are analyzed in view of the requirements for an efficient hydrogen cell factory. A special emphasis is put on the tight regulation
of hydrogen production in C. saccharolyticus by both redox and energy metabolism. Suggestions for strategies to overcome the current challenges facing the potential use
of the organism in hydrogen production are also discussed. 相似文献