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41.
Signaling via heterotrimeric G-proteins is evoked by agonist-mediated stimulation of seven transmembrane spanning receptors (GPCRs). During the last decade it has become apparent that Gα subunits can be activated by receptor-independent mechanisms. Ric-8 belongs to a highly conserved protein family that regulates heterotrimeric G-protein function, acting as a non-canonical guanine nucleotide exchange factors (GEF) over a subset of Gα subunits. In this review we discuss the roles of Ric-8 in the regulation of diverse cell functions, emphasizing the contribution of its multiple domain protein structure in these diverse functions. 相似文献
42.
Maike H. Hinrichs Avesta Jalal Bernhard Brenner Eckhard Mandelkow Satish Kumar Tim Scholz 《The Journal of biological chemistry》2012,287(46):38559-38568
Current models for the intracellular transport of Tau protein suggest motor protein-dependent co-transport with microtubule fragments and diffusion of Tau in the cytoplasm, whereas Tau is believed to be stationary while bound to microtubules and in equilibrium with free diffusion in the cytosol. Observations that members of the microtubule-dependent kinesin family show Brownian motion along microtubules led us to hypothesize that diffusion along microtubules could also be relevant in the case of Tau. We used single-molecule total internal reflection fluorescence microscopy to probe for diffusion of individual fluorescently labeled Tau molecules along microtubules. This allowed us to avoid the problem that microtubule-dependent diffusion could be masked by excess of labeled Tau in solution that might occur in in vivo overexpression experiments. We found that approximately half of the individually detected Tau molecules moved bidirectionally along microtubules over distances up to several micrometers. Diffusion parameters such as diffusion coefficient, interaction time, and scanned microtubule length did not change with Tau concentration. Tau binding and diffusion along the microtubule lattice, however, were sensitive to ionic strength and pH and drastically reduced upon enzymatic removal of the negatively charged C termini of tubulin. We propose one-dimensional Tau diffusion guided by the microtubule lattice as one possible additional mechanism for Tau distribution. By such one-dimensional microtubule lattice diffusion, Tau could be guided to both microtubule ends, i.e. the sites where Tau is needed during microtubule polymerization, independently of directed motor-dependent transport. This could be important in conditions where active transport along microtubules might be compromised. 相似文献
43.
44.
Kapoor M Wang JC Bertelsen S Bucholz K Budde JP Hinrichs A Agrawal A Brooks A Chorlian D Dick D Hesselbrock V Foroud T Kramer J Kuperman S Manz N Nurnberger J Porjesz B Rice J Tischfield J Xuei X Schuckit M Edenberg HJ Bierut LJ Goate AM 《PloS one》2012,7(3):e33513
Several genome-wide association and candidate gene studies have linked chromosome 15q24-q25.1 (a region including the CHRNA5-CHRNA3-CHRNB4 gene cluster) with alcohol dependence, nicotine dependence and smoking-related illnesses such as lung cancer and chronic obstructive pulmonary disease. To further examine the impact of these genes on the development of substance use disorders, we tested whether variants within and flanking the CHRNA5-CHRNA3-CHRNB4 gene cluster affect the transition to daily smoking (individuals who smoked cigarettes 4 or more days per week) in a cross sectional sample of adolescents and young adults from the COGA (Collaborative Study of the Genetics of Alcoholism) families. Subjects were recruited from families affected with alcoholism (either as a first or second degree relative) and the comparison families. Participants completed the SSAGA interview, a comprehensive assessment of alcohol and other substance use and related behaviors. Using the Quantitative trait disequilibrium test (QTDT) significant association was detected between age at onset of daily smoking and variants located upstream of CHRNB4. Multivariate analysis using a Cox proportional hazards model further revealed that these variants significantly predict the age at onset of habitual smoking among daily smokers. These variants were not in high linkage disequilibrium (0.28相似文献
45.
Wegener G Bausch M Holler T Thang NM Prieto Mollar X Kellermann MY Hinrichs KU Boetius A 《Environmental microbiology》2012,14(6):1517-1527
Sub‐seafloor sediments are populated by large numbers of microbial cells but not much is known about their metabolic activities, growth rates and carbon assimilation pathways. Here we introduce a new method enabling the sensitive detection of microbial lipid production and the distinction of auto‐ and heterotrophic carbon assimilation. Application of this approach to anoxic sediments from a Swedish fjord allowed to compare the activity of different functional groups, the growth and turnover times of the bacterial and archaeal communities. The assay involves dual stable isotope probing (SIP) with deuterated water (D2O) and 13CDIC (d issolved i norganic c arbon). Culture experiments confirmed that the D content in newly synthesized lipids is in equilibrium with the D content in labelled water, independent of whether the culture grew hetero‐ or autotrophically. The ratio of 13CDIC to D2O incorporation enables distinction between these two carbon pathways in studies of microbial cultures and in environmental communities. Furthermore, D2O‐SIP is sufficiently sensitive to detect the formation of few hundred cells per day in a gram of sediment. In anoxic sediments from a Swedish fjord, we found that > 99% of newly formed lipids were attributed to predominantly heterotrophic bacteria. The production rate of bacterial lipids was highest in the top 5 cm and decreased 60‐fold below this depth while the production rate of archaeal lipids was rather low throughout the top meter of seabed. The contrasting patterns in the rates of archaeal and bacterial lipid formation indicate that the factors controlling the presence of these two lipid groups must differ fundamentally. 相似文献
46.
Strapoc D Picardal FW Turich C Schaperdoth I Macalady JL Lipp JS Lin YS Ertefai TF Schubotz F Hinrichs KU Mastalerz M Schimmelmann A 《Applied and environmental microbiology》2008,74(8):2424-2432
A series of molecular and geochemical studies were performed to study microbial, coal bed methane formation in the eastern Illinois Basin. Results suggest that organic matter is biodegraded to simple molecules, such as H(2) and CO(2), which fuel methanogenesis and the generation of large coal bed methane reserves. Small-subunit rRNA analysis of both the in situ microbial community and highly purified, methanogenic enrichments indicated that Methanocorpusculum is the dominant genus. Additionally, we characterized this methanogenic microorganism using scanning electron microscopy and distribution of intact polar cell membrane lipids. Phylogenetic studies of coal water samples helped us develop a model of methanogenic biodegradation of macromolecular coal and coal-derived oil by a complex microbial community. Based on enrichments, phylogenetic analyses, and calculated free energies at in situ subsurface conditions for relevant metabolisms (H(2)-utilizing methanogenesis, acetoclastic methanogenesis, and homoacetogenesis), H(2)-utilizing methanogenesis appears to be the dominant terminal process of biodegradation of coal organic matter at this location. 相似文献
47.
Lockridge O Xue W Gaydess A Grigoryan H Ding SJ Schopfer LM Hinrichs SH Masson P 《The Journal of biological chemistry》2008,283(33):22582-22590
Human albumin is thought to hydrolyze esters because multiple equivalents of product are formed for each equivalent of albumin. Esterase activity with p-nitrophenyl acetate has been attributed to turnover at tyrosine 411. However, p-nitrophenyl acetate creates multiple, stable, acetylated adducts, a property contrary to turnover. Our goal was to identify residues that become acetylated by p-nitrophenyl acetate and determine the relationship between stable adduct formation and turnover. Fatty acid-free human albumin was treated with 0.5 mm p-nitrophenyl acetate for 5 min to 2 weeks, or with 10 mm p-nitrophenyl acetate for 48 h to 2 weeks. Aliquots were digested with pepsin, trypsin, or GluC and analyzed by mass spectrometry to identify labeled residues. Only Tyr-411 was acetylated within the first 5 min of reaction with 0.5 mm p-nitrophenyl acetate. After 0.5-6 h there was partial acetylation of 16-17 residues including Asp-1, Lys-4, Lys-12, Tyr-411, Lys-413, and Lys-414. Treatment with 10 mm p-nitrophenyl acetate resulted in acetylation of 59 lysines, 10 serines, 8 threonines, 4 tyrosines, and Asp-1. When Tyr-411 was blocked with diisopropylfluorophosphate or chlorpyrifos oxon, albumin had normal esterase activity with beta-naphthyl acetate as visualized on a nondenaturing gel. However, after 82 residues had been acetylated, esterase activity was almost completely inhibited. The half-life for deacetylation of Tyr-411 at pH 8.0, 22 degrees C was 61 +/- 4 h. Acetylated lysines formed adducts that were even more stable. In conclusion, the pseudo-esterase activity of albumin is the result of irreversible acetylation of 82 residues and is not the result of turnover. 相似文献
48.
Larson MA Bressani R Sayood K Corn JE Berger JM Griep MA Hinrichs SH 《Nucleic acids research》2008,36(16):5260-5269
The placement of the extreme thermophile Aquifex aeolicus in the bacterial phylogenetic tree has evoked much controversy. We investigated whether adaptations for growth at high temperatures would alter a key functional component of the replication machinery, specifically DnaG primase. Although the structure of bacterial primases is conserved, the trinucleotide initiation specificity for A. aeolicus was hypothesized to differ from other microbes as an adaptation to a geothermal milieu. To determine the full range of A. aeolicus primase activity, two oligonucleotides were designed that comprised all potential trinucleotide initiation sequences. One of the screening templates supported primer synthesis and the lengths of the resulting primers were used to predict possible initiation trinucleotides. Use of trinucleotide-specific templates demonstrated that the preferred initiation trinucleotide sequence for A. aeolicus primase was 5′-d(CCC)-3′. Two other sequences, 5′-d(GCC)-3′ and d(CGC)-3′, were also capable of supporting initiation, but to a much lesser degree. None of these trinucleotides were known to be recognition sequences used by other microbial primases. These results suggest that the initiation specificity of A. aeolicus primase may represent an adaptation to a thermophilic environment. 相似文献
49.
50.
Dependence of the Post-Illumination Burst of CO2 on Temperature, Light, CO2 , and O2 Concentration in Wheat (Triticum aestivum) 总被引:3,自引:0,他引:3
The effect of environmental factors on the post-illumination burst of CO2 (PIB) and O2 inhibition of apparent photosynthesis (APS) in wheat (Triticum aestivum L.) was studied in an open gas exchange system utilizing the mathematics of non-steady-state systems. Two components of inhibition by O2 are suggested: one is caused by photorespiration as measured from the maximum rate of the PIB, and the second is direct inhibition as taken as APS2%O2— (APSx%O2+ PIBx%O2) where X is the oxygen concentration. A primary PIB which occurred from 16–28 s after the darkening of the foliage was attributed to photorespiration. No primary PIB was observed at 2% O2. At a CO2 concentration of 100 μ/1 in the atmosphere (about 2.5 μM based on leaf intercellular concentration) and at 30°C and 145 nE/cm2 nE/cm2·s, APS decreased curve-linearly with increasing O2 and reached an O2 compensation point of 560 μM (48% by volume), above which there was a net loss of CO2 in the light. The PIB increased with increasing O2 and became saturated at about 500 μM O2 but decreased above 900 μM O2. Direct inhibition of photosynthesis by O2 increased with increasing O2 concentration. Decreasing CO2 concentration had an effect on the magnitude of the PIB similar to that of increasing O2. At 30°C and 21% O2, the PIB increased with decreasing CO2 down to the CO2 compensation point (I) of 1.4 μM (47 μM/l). Below Γ, both PIB and CO2 evolution into the air in the light (at 21% O2) increased and then decreased at CO2 below 0.8 μM. The ratio of the PIB to APS2% o O2 increased linearly with increasing O2/CO2 ratio where O2 was held constant at 21% and CO2 was varied from 1.4 to 8.5 μM, while direct inhibition of photosynthesis expressed as a proportion of APS2%O2 remained constant over this range. At low CO2 concentration photorespiration as estimated by the PIB is the major part of O2 photosynthesis, while at atmospheric CO2 levels, direct inhibition is the major component. The PIB and APS at 2% and 21% O2 increased hyperbolically with increasing irradiance and all became light-saturated at about 65 nE/cm2 s. The percentage total O2 inhibition of photosynthesis remained constant with increasing irradiance as did the relative contribution of direct O2 inhibition or photorespiration (PIB) to total O2 inhibition. The PIB and APS at 21% O2 had similar temperature optima of 30°C when experimental conditions were adjusted to provide a constant internal O2/CO2 solubility ratio at varying temperatures. However, with a constant external CO2 concentration, the temperature optimum for the PIB shifted upward to 35°C while that for APS at 21% O2 remained at 30°C, which may be due to an increased O2/CO2 concentration in the leaf with increasing temperature. 相似文献