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31.
Picou RA Schrum DP Ku G Cerqua RA Kheterpal I Gilman SD 《Analytical biochemistry》2012,425(2):104-112
The separation and detection of individual amyloid beta (Aβ) aggregates by capillary electrophoresis with laser-induced fluorescence detection (CE-LIF) was demonstrated. Samples were prepared with either Aβ (1-40) or Aβ (1-42) peptides and were characterized by CE with ultraviolet (UV) absorbance detection and transmission electron microscopy (TEM). Using thioflavin T (ThT) in the electrophoresis buffer, electrophoresis of aggregate-containing samples (5.0-s injection) produced up to several hundred narrow (< 20 ms FWHM [full width at half maximum]) fluorescence peaks. Injection of Aβ (1-40) monomer samples resulted in no additional peaks compared with controls. The CE-LIF results were validated by bulk ThT fluorescence measurements for the same samples. The potential of laser-induced fluorescence anisotropy (LIFA) with CE to characterize individual Aβ aggregates also was investigated. 相似文献
32.
Regulation of critical cellular functions, including Ca2+-dependent gene expression, is determined by the temporal and spatial aspects of agonist-induced Ca2+ signals. Stimulation of cells with physiological concentrations of agonists trigger increases [Ca2+]i due to intracellular Ca2+ release and Ca2+ influx. While Orai1-STIM1 channels account for agonist-stimulated [Ca2+]i increase as well as activation of NFAT in cells such as lymphocytes, RBL and mast cells, both Orai1-STIM1 and TRPC1-STIM1 channels contribute to [Ca2+]i increases in human submandibular gland (HSG) cells. However, only Orai1-mediated Ca2+ entry regulates the activation of NFAT in HSG cells. Since both TRPC1 and Orai1 are activated following internal Ca2+ store depletion in these cells, it is not clear how the cells decode individual Ca2+ signals generated by the two channels for the regulation of specific cellular functions. Here we have examined the contributions of Orai1 and TRPC1 to carbachol (CCh)-induced [Ca2+]i signals and activation of NFAT in single cells. We report that Orai1-mediated Ca2+ entry generates [Ca2+]i oscillations at different [CCh], ranging from very low to high. In contrast, TRPC1-mediated Ca2+ entry generates sustained [Ca2+]i elevation at high [CCh] and contributes to frequency of [Ca2+]i oscillations at lower [agonist]. More importantly, the two channels are coupled to activation of distinct Ca2+ dependent gene expression pathways, consistent with the different patterns of [Ca2+]i signals mediated by them. Nuclear translocation of NFAT and NFAT-dependent gene expression display “all-or-none” activation that is exclusively driven by local [Ca2+]i generated by Orai1, independent of global [Ca2+]i changes or TRPC1-mediated Ca2+ entry. In contrast, Ca2+ entry via TRPC1 primarily regulates NFκB-mediated gene expression. Together, these findings reveal that Orai1 and TRPC1 mediate distinct local and global Ca2+ signals following agonist stimulation of cells, which determine the functional specificity of the channels in activating different Ca2+-dependent gene expression pathways. 相似文献
33.
Muoio DM Noland RC Kovalik JP Seiler SE Davies MN DeBalsi KL Ilkayeva OR Stevens RD Kheterpal I Zhang J Covington JD Bajpeyi S Ravussin E Kraus W Koves TR Mynatt RL 《Cell metabolism》2012,15(5):764-777
The concept of "metabolic inflexibility" was first introduced to describe the failure of insulin-resistant human subjects to appropriately adjust mitochondrial fuel selection in response to nutritional cues. This phenomenon has since gained increasing recognition as a core component of the metabolic syndrome, but the underlying mechanisms have remained elusive. Here, we identify an essential role for the mitochondrial matrix enzyme, carnitine acetyltransferase (CrAT), in regulating substrate switching and glucose tolerance. By converting acetyl-CoA to its membrane permeant acetylcarnitine ester, CrAT regulates mitochondrial and intracellular carbon trafficking. Studies in muscle-specific Crat knockout mice, primary human skeletal myocytes, and human subjects undergoing L-carnitine supplementation support a model wherein CrAT combats nutrient stress, promotes metabolic flexibility, and enhances insulin action by permitting mitochondrial efflux of excess acetyl moieties that otherwise inhibit key regulatory enzymes such as pyruvate dehydrogenase. These findings offer therapeutically relevant insights into the molecular basis of metabolic inflexibility. 相似文献
34.
Response of benzoate along with phenol to different anaerobic inocula has been investigated in batch reactors. In Phase I, the anaerobic biodegradability of benzoate and phenol were evaluated using (a) washed acclimatized granular sludge (WAGS) collected from a passive phenol fed bench-scale up-flow anaerobic sludge blanket reactor (UASBR) and (b) unacclimatized flocculent sludge (UFS) from a UASB based sewage treatment plant (STP). The effect of varying concentrations of benzoate has been investigated in Phase II using acclimatized granular sludge (AGS) from a bench-scale UASBR. Extent of degradation of benzoate was more than the phenol. Increasing benzoate COD from 2500 to 11,700mg/L, resulted in decrease in (i) rate constant, k from 0.79 to 0.11/d and (ii) ultimate biochemical methane potential (microb, g CH4-COD formed/g benzoate COD) from 84% to 60%. Temporal trend conforming to logistic S-curve indicated stressed conditions at higher benzoate concentration. Benzoate degradation was found to be sensitive to nature as well as quantity i.e. food to microorganism (F/M) of inocula used. 相似文献
35.
36.
P. Giridhar E. P. Indu K. Vinod A. Chandrashekar G. A. Ravishankar 《Acta Physiologiae Plantarum》2004,26(3):299-305
For the first time direct somatic embryogenesis from hypocotyl explants of in vitro regenerated plantlets of C. arabica and C. canephora was achieved on modified MS medium containing 10 – 70 μM silver nitrate supplemented with 1.1 μM N6 benzyladenine and 2.85 μM indole-3-acetic acid. A maximum of 144.1±7.3 and 68.7±3.3 embryos per explant were produced at
40 μM silver nitrate in C. canephora and C. arabica respectively. Only yellow friable embryogenic callus obtained from the cut edges of most of leaf explants of both C. arabica and C. canephora at all concentrations of silver nitrate were tried in this experiment. Formation of secondary embryos from stage I primary
embryos (small yellow, round, globular embryos) was more (28.23±1.3) at 60 μM silver nitrate in C. canephora, while 40 μM silver nitrate supported more of secondary embryo formation in C. arabica (40.5±1.2). When stage II (green globular round matured embryos) and stage III primary embryos (tubular stage embryos) were
used, secondary embryo formation was very small and many of these embryos developed into plantlets and some of them even rooted.
By using these protocols within 45 – 60 days it is possible to get secondary embryos from primary embryos and direct somatic
embryos from hypocotyls of in vitro plantlets in both these Coffea species. 相似文献
37.
AbstractCircadian rhythms are endogenous, and synchronize biological functions at the most suited time of the day. Insects like other organism display a wide array of circadian functions, which are controlled by a central timing system, in coordination with the peripheral clocks found in many tissues. Many insect behaviours including locomotion, courtship, mating, egg laying and photoperiodism, are influenced by the circadian systems. In this mini-review, we briefly describe the involvement of circadian clocks in various physiological processes and correlate their functions in insect life, focusing on lepidopteran pests (major group of Indian crop pests) and discuss their role(s) in the development of effective pest management strategy. 相似文献
38.
We have isolated cell wall peptidoglycan associated proteins (CW-Pr) of Mycobacterium tuberculosis H37Ra by chemical treatment with trifluoromethanesulfonic acid:anisole (2:1), which further resolved into 71, 60 and 45 kDa proteins on SDS-PAGE. A study was carried out to investigate the immunoreactivity of these proteins with blood samples from 4 categories, including 15 tuberculous patients (TB), 5 tuberculous patients on ATT (TBT), 10 PPD non-reactive healthy controls (HPPD?) and 11 PPD reactive healthy controls (HPPD+). Comparing the proliferative responses to cell wall protein antigens, it was observed that the 71 kDa protein gave maximum stimulation with PBMCs from the TB and HPPD+ groups. The adherent PBMCs from the TB group also demonstrated enhanced phagocytosis, particularly in the presence of 71 and 45 kDa proteins, and the phagocytic index was significantly higher (P < 0.05) than the TBT group. However, PBMCs from of the groups recognized the 60 kDa cell wall antigen. Our results suggest that the 71 kDa protein from the cell wall of M. tuberculosis is highly immunogenic. 相似文献
39.
40.
Molten globule-like intermediates have been shown to occur during protein folding and are thought to be involved in protein translocation and membrane insertion. However, the determinants of molten globule stability and the extent of specific packing in molten globules is currently unclear. Using far- and near-UV CD and intrinsic and ANS fluorescence, we show that four periplasmic binding proteins (LBP, LIVBP, MBP, and RBP) form molten globules at acidic pH values ranging from 3.0 to 3.4. Only two of these (LBP and LIVBP) have similar sequences, but all four proteins adopt similar three-dimensional structures. We found that each of the four molten globules binds to its corresponding ligand without conversion to the native state. Ligand binding affinity measured by isothermal titration calorimetry for the molten globule state of LIVBP was found to be comparable to that of the corresponding native state, whereas for LBP, MBP, and RBP, the molten globules bound ligand with approximately 5-30-fold lower affinity than the corresponding native states. All four molten globule states exhibited cooperative thermal unfolding assayed by DSC. Estimated values of DeltaCp of unfolding show that these molten globule states contain 28-67% of buried surface area relative to the native states. The data suggest that molten globules of these periplasmic binding proteins retain a considerable degree of long range order. The ability of these sequentially unrelated proteins to form highly ordered molten globules may be related to their large size as well as an intrinsic property of periplasmic binding protein folds. 相似文献