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191.
Is hypusine essential for eukaryotic cell proliferation?   总被引:6,自引:0,他引:6  
  相似文献   
192.
Year to year variation and vertical distributions of epipelagic Zooplankton around Elephant Island and King George Island were examined with samples collected with bongo nets and a 1 m2 MOCNESS during the austral summers (Jan–Feb.) of 1988, 1989 and 1990. Copepods were the major components of epipelagic Zooplankton (in numbers) with dominance of Metridia gerlachei (1988 and 1989) and small calanoids and cyclopoids (1990). Euphausiids and salps were the next most abundant groups. The percent composition of euphausiids decreased from 1988 to 1990 while that of salps increased. The abundance of salps exceeded euphausiids and major taxa of copepods in 1990. Local patches of polychaetes and amphipods were also found. Statistically significant annual variations with increased numbers in 1990 were found by analyses of variance in total abundance, abundances of copepods, salps, chaetognaths and amphipods, but abundances of euphausiids, polychaetes and fishes showed no significant annual variations. When the study area was divided geographically, horizontal variability in abundance within each year showed no significance in total abundance, abundances of copepods, euphausiids, amphipods and fishes, but significance in salps, polychaetes and chaetognaths. Results of site clustering based on covariances of abundances of eleven major taxa were well matched, though not perfect, with the distribution of surface water temperatures which could be used as a tracer of source water masses suggesting that spatial variation was related to hydrodynamic conditions. Factor analyses showed that annual and spatial variations in abundance were mainly caused by only two taxa, Metridia gerlachei and salps (mostly Salpa thompsoni). These two taxa were responsible for about 60% and 30% of total variance, respectively, and were useful indicators of the interannual variation. That is, 1988 and 1989 were the years of M. gerlachei, and 1990 was the year of salps. From vertically stratified MOCNESS samples, it was shown that the major taxa in this study area were active vertical migrators. While most samples obtained by relatively shallow tows (uppermost 100 m depth) were composed of exclusively one or two taxa, those from relatively deep tows (down to 200 m) showed various patterns of vertical stratification suggesting that the patterns of vertical migration were species specific. Species specific ontogenetic vertical migration associated with elevated habitat temperatures also seemed to be responsible for the annual variation in zooplankton distribution in the upper water column.  相似文献   
193.
This paper is concerned with using multivariate binary observations to estimate the probabilities of unobserved classes with scientific meanings. We focus on the setting where additional information about sample similarities is available and represented by a rooted weighted tree. Every leaf in the given tree contains multiple samples. Shorter distances over the tree between the leaves indicate a priori higher similarity in class probability vectors. We propose a novel data integrative extension to classical latent class models with tree-structured shrinkage. The proposed approach enables (1) borrowing of information across leaves, (2) estimating data-driven leaf groups with distinct vectors of class probabilities, and (3) individual-level probabilistic class assignment given the observed multivariate binary measurements. We derive and implement a scalable posterior inference algorithm in a variational Bayes framework. Extensive simulations show more accurate estimation of class probabilities than alternatives that suboptimally use the additional sample similarity information. A zoonotic infectious disease application is used to illustrate the proposed approach. The paper concludes by a brief discussion on model limitations and extensions.  相似文献   
194.
Cav3.1 T-type Ca2+ channels play pivotal roles in neuronal low-threshold spikes, visceral pain, and pacemaker activity. Phosphorylation has been reported to potently regulate the activity and gating properties of Cav3.1 channels. However, systematic identification of phosphorylation sites (phosphosites) in Cav3.1 channel has been poorly investigated. In this work, we analyzed rat Cav3.1 protein expressed in HEK-293 cells by mass spectrometry, identified 30 phosphosites located at the cytoplasmic regions, and illustrated them as a Cav3.1 phosphorylation map which includes the reported mouse Cav3.1 phosphosites. Site-directed mutagenesis of the phosphosites to Ala residues and functional analysis of the phospho-silent Cav3.1 mutants expressed in Xenopus oocytes showed that the phospho-silent mutation of the N-terminal Ser18 reduced its current amplitude with accelerated current kinetics and negatively shifted channel availability. Remarkably, the phospho-silent mutations of the C-terminal Ser residues (Ser1924, Ser2001, Ser2163, Ser2166, or Ser2189) greatly reduced their current amplitude without altering the voltage-dependent gating properties. In contrast, the phosphomimetic Asp mutations of Cav3.1 on the N- and C-terminal Ser residues reversed the effects of the phospho-silent mutations. Collectively, these findings demonstrate that the multiple phosphosites of Cav3.1 at the N- and C-terminal regions play crucial roles in the regulation of the channel activity and voltage-dependent gating properties.  相似文献   
195.
196.
T Kline  H Park  L R Meyerson 《Life sciences》1989,45(21):1997-2005
The binding of [3H] 8-OH-DPAT to membrane-bound 5-HT1A receptors from bovine hippocampus was saturable and corresponded to a single high-affinity state. Solubilization of the bovine hippocampal membranes with 10 mM CHAPS containing 200 mM NaCl, renders a preparation which binds [3H] 8-OH-DPAT with high-affinity (Kd = 1.9 nM) and is guanine nucleotide sensitive and ketanserin insensitive. 50% of [3H] 8-OH-DPAT binding activity is solubilized. The presence of GMP-P(NH)P promotes a low-affinity (Kd = 9.6 nM) state which is characteristic of receptors coupled to G-proteins. GMP-P(NH)P markedly accelerates the dissociation [3H] 8-OH-DPAT from solubilized membranes while having negligible effects on association. Thus, the agonist can activate the terniary complex rather than to promote its formation. 8-OH DPAT, WB 4101 and 5-carboxamidotryptamine dose responsively inhibit soluble [3H] 8-OH-DPAT binding with IC(50) values of 16.1, 15.6 and 1.3 nM, respectively. The CHAPS solubilized membrane preparation retains many of the [3H] 8-OH-DPAT binding characteristics of the membrane bound form.  相似文献   
197.
Presented in the article is a method for constructing a graphical model of an FMS by using a new modeling tool called JR-net (Job Resource relation-net). JR-net is an object-oriented graphical tool for modeling automated manufacturing systems (AMSs), such as FMSs, FASs, and AS/RSs. As with the object-oriented modeling paradigm of Rumbaugh et al. (1991), the JR-net modeling framework supports the three stages of models: static layout model (object model); job flow model (functional model); and supervisory control model (dynamic model). In this article, the existing JR-net structure (Park 1992, Han et al., 1995) is extended further to make it a graphical tool for FMS modeling. Using the extended JR-net, a step-by-step procedure for constructing a graphical model of FMSs is presented. Also addressed are issues of classifying FMSs in terms of their generic functions and of utilizing the JR-net model of FMSs.  相似文献   
198.
Isoproterenol is a chiral catecholamine with a half-life of elimination of less than 10 min. In order to study the pharmacokinetics of this compound using microdialysis sampling, an analytical method was needed which could resolve the individual enantiomers of isoproterenol and required less than 1 μl of sample. A capillary electrophoretic method using a run buffer containing methyl-O-β-cyclodextrin as a chiral recognition agent was developed which could resolve the enantiomers of isoproterenol. The detection limits using UV absorbance detection were found to be too high to determine the concentration of isoproterenol in plasma for a sufficient time following administration to establish the pharmacokinetics. The detection limits were decreased three orders of magnitude to 3 ng/ml by using an amperometric detector. The detection limits were decreased to 0.6 ng/ml using an on-column concentration technique in which peak stacking was accomplished by following the sample injection with a plug of acid.  相似文献   
199.
Summary The unusual amino acid hypusine [N -(4-amino-2-hydroxybutyl)lysine] is a unique component of one cellular protein, eukaryotic translation initiation factor 5A (eIF-5A, old terminology, eIF-4D). It is formed posttranslationally and exclusively in this protein in two consecutive enzymatic reactions, (i) modification of a single lysine residue of the eIF-5A precursor protein by the transfer of the 4-aminobutyl moiety of the polyamine spermidine to its-amino group to form the intermediate, deoxyhypusine [N -(4-aminobutyl)lysine] and (ii) subsequent hydroxylation of this intermediate to form hypusine. The amino acid sequences surrounding the hypusine residue are strictly conserved in all eukaryotic species examined, suggesting the fundamental importance of this amino acid throughout evolution. Hypusine is required for the activity of eIF-5Ain vitro. There is strong evidence that hypusine and eIF-5A are vital for eukaryotic cell proliferation. Inactivation of both of the eIF-5A genes is lethal in yeast and the hypusine modification appears to be a requirement for yeast survival (Schnier et al., 1991 [Mol Cell Biol 11: 3105–3114]; Wöhl et al., 1993 [Mol Gen Genet 241: 305–311]). Furthermore, inhibitors of either of the hypusine biosynthetic enzymes, deoxyhypusine synthase or deoxyhypusine hydroxylase, exert strong anti-proliferative effects in mammalian cells, including many human cancer cell lines. These inhibitors hold potential as a new class of anticancer agents, targeting one specific eukaryotic cellular reaction, hypusine biosynthesis.  相似文献   
200.
Salmonella typhimurium possesses an adaptive response to acid that increases survival during exposure to extremely low pH values. The acid tolerance response (ATR) includes both log-phase and stationary-phase systems. The log-phase ATR appears to require two components for maximum acid tolerance, namely an inducible pH homeostasis system, and a series of acid-shock proteins. We have discovered one of what appears to be a series of inducible exigency pH homeostasis systems that contribute to acid tolerance in extreme acid environments. The low pH-inducible lysine decarboxylase was shown to contribute significantly to pH homeostasis in environments as low as pH 3.0. Under the conditions tested, both lysine decarboxylase and σs-dependent acid-shock proteins were required for acid tolerance but only lysine decarboxylase contributed to pH homeostasis. The cadBA operon encoding lysine decarboxylase and a lysine/cadaverine antiporter were cloned from S. typhimurium and were found to be 79% homologous to the cadBA operon from Escherichia coli . The results suggest that S. typhimurium has a variety of means of fulfilling the pH homeostasis requirement of the ATR in the form of inducible amino acid decarboxylases.  相似文献   
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