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921.
Pamplona R Naudí A Gavín R Pastrana MA Sajnani G Ilieva EV Del Río JA Portero-Otín M Ferrer I Requena JR 《Free radical biology & medicine》2008,45(8):1159-1166
The basic molecular underpinnings of the pathological changes that unfold in prion disease remain elusive. A key role of increased oxidative stress has been hypothesized. Given the transient nature of most intermediate molecules implicated, increased oxidative stress is better assessed by quantitating the damage it causes to macromolecules. We used mass spectrometry-based methods to measure specific products of protein oxidation, glycoxidation, and lipoxidation in brains from patients suffering from Creutzfeldt-Jakob disease and Syrian hamsters affected by scrapie. In both cases, increased amounts of glutamic and aminoadipic semialdehydes, products of metal-catalyzed oxidation, malondialdehydelysine (a product of lipoxidation), N-epsilon-carboxyethyllysine (a product of glycoxidation), and N-epsilon-carboxymethyllysine (generated by lipoxidation and glycoxidation) were measured. PrP(Sc), the infectious isoform of the prion protein that accumulates in prion disease, was itself shown to be a target of increased oxidative modification. These changes were accompanied by alterations in fatty acid composition and increased phosphorylation of ERK(1/2) and p38, protein kinases known to respond to increased flows of ROS. These data support an important role of oxidative damage in the pathology of prion disease. 相似文献
922.
Patricia Torres-Cañabate Eric A. Davidson Ekaterina Bulygina Roberto García-Ruiz Jose A. Carreira 《Biogeochemistry》2008,91(1):1-11
Evidence for abiotic immobilization of nitrogen (N) in soil is accumulating, but remains controversial. Identifying the fate
of N from atmospheric deposition is important for understanding the N cycle of forest ecosystems. We studied soils of two
Abies pinsapo fir forests under Mediterranean climate seasonality in southern Spain—one with low N availability and the other with symptoms
of N saturation. We hypothesized that biotic and abiotic immobilization of nitrate (NO3
−) would be lower in soils under these forests compared to more mesic temperate forests, and that the N saturated stand would
have the lowest rates of NO3
− immobilization. Live and autoclaved soils were incubated with added 15NO3
− (10 μg N g−1 dry soil; 99% enriched) for 24 h, and the label was recovered as total dissolved-N, NO3
−, ammonium (NH4
+), or dissolved organic-N (DON). To evaluate concerns about possible iron interference in analysis of NO3
− concentrations, both flow injection analysis (FIA) and ion chromatography (IC) were applied to water extracts, soluble iron
was measured in both water and salt extracts, and standard additions of NO3
− to salt extracts were analyzed. Good agreement between FIA and IC analysis, low concentrations of soluble Fe, and 100% (±3%)
recovery of NO3
− standard additions all pointed to absence of an interference problem for NO3
− quantification. On average, 85% of the added 15NO3
− label was recovered as 15NO3
−, which supports our hypothesis that rates of immobilization were generally low in these soils. A small amount (mean = 0.06 μg N g−1 dry soil) was recovered as 15NH4
+ in live soils and none in sterilized soils. Mean recovery as DO15N ranged from 0.6 to 1.5 μg N g−1 dry soil, with no statistically significant effect of sterilization or soil type, indicating that this was an abiotic process
that occurred at similar rates in both soils. These results demonstrate a detectable, but modest rate of abiotic immobilization
of NO3
− to DON, supporting our first hypothesis. These mineral soils may not have adequate carbon availability to support the regeneration
of reducing microsites needed for high rates of NO3
− reduction. Our second hypothesis regarding lower expected abiotic immobilization in soils from the N-saturated site was not
supported. The rates of N deposition in this region may not be high enough to have swamped the capacity for soil NO3
− immobilization, even in the stand showing some symptoms of N saturation. A growing body of evidence suggests that soil abiotic
NO3
− immobilization is common, but that rates are influenced by a combination of factors, including the presence of plentiful
available carbon, reduced minerals in anaerobic microsites and adequate NO3
− supply. 相似文献
923.
Structural basis of dcp2 recognition and activation by dcp1 总被引:3,自引:0,他引:3
She M Decker CJ Svergun DI Round A Chen N Muhlrad D Parker R Song H 《Molecular cell》2008,29(3):337-349
A critical step in mRNA degradation is the removal of the 5' cap structure, which is catalyzed by the Dcp1-Dcp2 complex. The crystal structure of an S. pombe Dcp1p-Dcp2n complex combined with small-angle X-ray scattering analysis (SAXS) reveals that Dcp2p exists in open and closed conformations, with the closed complex being, or closely resembling, the catalytically more active form. This suggests that a conformational change between these open and closed complexes might control decapping. A bipartite RNA-binding channel containing the catalytic site and Box B motif is identified with a bound ATP located in the catalytic pocket in the closed complex, suggesting possible interactions that facilitate substrate binding. Dcp1 stimulates the activity of Dcp2 by promoting and/or stabilizing the closed complex. Notably, the interface of Dcp1 and Dcp2 is not fully conserved, explaining why the Dcp1-Dcp2 interaction in higher eukaryotes requires an additional factor. 相似文献
924.
Long-term bird population changes in response to natural or anthropogenic factors have been relatively well documented in the temperate zone, but rarely in the tropics, where there are few long-term data sets. Here, we analyze a 25-yr sequence of records of two species of Lophura pheasants, Siamese Fireback L. diardi and Silver Pheasant L. nycthemera in Khao Yai, Thailand's oldest national park. These data suggest that the number and proportion of detections of the lowlands-inhabiting L. diardi have increased significantly in relation to those of the higher elevation inhabitant L. nycthemera . Environmental factors mediated by changing climate are the most plausible explanation for the changing proportions of sightings of the two species. Further work is needed to explore in detail microhabitat selection of these birds and whether changes in microsite conditions on the forest floor or other factors are driving the observed distribution. Long-term monitoring of the avifauna along an elevational gradient is also recommended in tandem with increased monitoring of local climatic conditions. 相似文献
925.
Reichenbach B Delalande JM Kolmogorova E Prier A Nguyen T Smith CM Holzschuh J Shepherd IT 《Developmental biology》2008,318(1):52-64
The zebrafish enteric nervous system (ENS), like those of all other vertebrate species, is principally derived from the vagal neural crest cells (NCC). The developmental controls that govern the migration, proliferation and patterning of the ENS precursors are not well understood. We have investigated the roles of endoderm and Sonic hedgehog (SHH) in the development of the ENS. We show that endoderm is required for the migration of ENS NCC from the vagal region to the anterior end of the intestine. We show that the expression of shh and its receptor ptc-1 correlate with the development of the ENS and demonstrate that hedgehog (HH) signaling is required in two phases, a pre-enteric and an enteric phase, for normal ENS development. We show that HH signaling regulates the proliferation of vagal NCC and ENS precursors in vivo. We also show the zebrafish hand2 is required for the normal development of the intestinal smooth muscle and the ENS. Furthermore we show that endoderm and HH signaling, but not hand2, regulate gdnf expression in the intestine, highlighting a central role of endoderm and SHH in patterning the intestine and the ENS. 相似文献
926.
Microtubule-associated proteins (MAPs) ensure the fidelity of chromosome segregation by controlling microtubule (MT) dynamics and mitotic spindle stability. However, many aspects of MAP function and regulation are poorly understood in a developmental context. We show that mars, which encodes a Drosophila melanogaster member of the hepatoma up-regulated protein family of MAPs, is essential for MT stabilization during early embryogenesis. As well as associating with spindle MTs in vivo, Mars binds directly to protein phosphatase 1 (PP1) and coimmunoprecipitates from embryo extracts with minispindles and Drosophila transforming acidic coiled-coil (dTACC), two MAPs that function as spindle assembly factors. Disruption of binding to PP1 or loss of mars function results in elevated levels of phosphorylated dTACC on spindles. A nonphosphorylatable form of dTACC is capable of rescuing the lethality of mars mutants. We propose that Mars mediates spatially controlled dephosphorylation of dTACC, which is critical for spindle stabilization. 相似文献
927.
Belogurov AA Kurkova IN Friboulet A Thomas D Misikov VK Zakharova MY Suchkov SV Kotov SV Alehin AI Avalle B Souslova EA Morse HC Gabibov AG Ponomarenko NA 《Journal of immunology (Baltimore, Md. : 1950)》2008,180(2):1258-1267
The pathologic role of autoantibodies in autoimmune disease is widely accepted. Recently, we reported that anti-myelin basic protein (MBP) serum Abs from multiple sclerosis (MS) patients exhibit proteolytic activity toward the autoantigen. The aim of this study is to determine MBP epitopes specific for the autoantibodies in MS and compare these data with those from other neuronal disorders (OND), leading to the generation of new diagnostic and prognostic criteria. We constructed a MBP-derived recombinant "epitope library" covering the entire molecule. We used ELISA and PAGE/surface-enhanced laser desorption/ionization mass spectroscopy assays to define the epitope binding/cleaving activities of autoantibodies isolated from the sera of 26 MS patients, 22 OND patients, and 11 healthy individuals. The levels of autoantibodies to MBP fragments 48-70 and 85-170 as well as to whole MBP and myelin oligodendrocyte glycoprotein molecules were significantly higher in the sera of MS patients than in those of healthy donors. In contrast, selective reactivity to the two MBP fragments 43-68 and 146-170 distinguished the OND and MS patients. Patients with MS (77% of progressive and 85% of relapsing-remitting) but only 9% of patients with OND and no healthy donors were positive for catalysis, showing pronounced epitope specificity to the encephalitogenic MBP peptide 81-103. This peptide retained its substrate properties when flanked with two fluorescent proteins, providing a novel fluorescent resonance energy transfer approach for MS studies. Thus, anti-MBP autoantibody-mediated, epitope-specific binding and cleavage may be regarded as a specific characteristic of MS compared with OND and healthy donors and may serve as an additional biomarker of disease progression. 相似文献
928.
Jared Jagdeo Julie K. Nguyen Derek Ho Erica B. Wang Evan Austin Andrew Mamalis Ramanjot Kaur Ekaterina Kraeva Joshua M. Schulman Chin‐Shang Li Samuel T. Hwang Ted Wun Emanual Maverakis R. Rivkah Isseroff 《Journal of biophotonics》2020,13(3)
Therapeutic applications of light emitting diode‐red light (LED‐RL) are expanding, yet data on its clinical effects are lacking. Our goal was to evaluate the safety of high fluence LED‐RL (≥160 J/cm2). In two phase I, single‐blind, dose escalation, randomized controlled trials, healthy subjects received LED‐RL or mock irradiation to the forearm thrice weekly for 3 weeks at fluences of 160‐640 J/cm2 for all skin types (STARS 1, n = 60) and at 480‐640 J/cm2 for non‐Hispanic Caucasians (STARS 2, n = 55). The primary outcome was the incidence of adverse events (AEs). The maximum tolerated dose was the highest fluence that did not elicit predefined AEs. Dose‐limiting AEs, including blistering and prolonged erythema, occurred at 480 J/cm2 in STARS 1 (n = 1) and 640 J/cm2 in STARS 2 (n = 2). AEs of transient erythema and hyperpigmentation were mild. No serious AEs occurred. We determined that LED‐RL is safe up to 320 J/cm2 for skin of color and 480 J/cm2 for non‐Hispanic Caucasian individuals. LED‐RL may exert differential cutaneous effects depending on race and ethnicity, with darker skin being more photosensitive. These findings may guide future studies to evaluate the efficacy of LED‐RL for the treatment of various diseases. 相似文献
929.
Ekaterina Trifonova Nikolai Nikitin Anatoly Gmyl Ekaterina Lazareva Olga Karpova 《Journal of biomolecular structure & dynamics》2013,31(8):1193-1201
Previously, we described some structural features of spherical particles (SPs) generated by thermal remodelling of the tobacco mosaic virus. The SPs represent a universal platform that could bind various proteins. Here, we report that entire isometric virions of heterogeneous nature bind non-specifically to the SPs. Formaldehyde (FA) was used for covalent binding of a virus to the SPs surface for stabilizing the SP—virus complexes. Transmission and high resolution scanning electron microscopy showed that the SPs surface was covered with virus particles. The architecture of SP–virion complexes was examined by immunologic methods. Mean diameters of SPs and SP–human enterovirus C and SP–cauliflower mosaic virus (CaMV) compositions were determined by nanoparticle tracking analysis (NTA) in liquid. Significantly, neither free SPs nor individual virions were detected by NTA in either FA-crosslinked or FA-untreated compositions. Entirely, all virions were bound to the SPs surface and the SP sites within the SP–CaMV complexes were inaccessible for anti-SP antibodies. Likewise, the SPs immunogenicity within the FA-treated SPs–CaMV compositions was negligible. Apparently, the SP antigenic sites were hidden and masked by virions within the compositions. Previously, we reported that the SPs exhibited adjuvant activity when foreign proteins/epitopes were mixed with or crosslinked to SPs. We found that immunogenicity of entire CaMV crosslinked to SP was rather low which could be due to the above-mentioned masking of the SPs booster. Contrastingly, immunogenicity of the FA-untreated compositions increased significantly, presumably, due to partial release of virions and unmasking of some SPs-buster sites after animals immunization. 相似文献
930.
Alexander Averianov Ekaterina Obraztsova Igor Danilov Jianhua Jin 《Historical Biology》2013,25(9):1115-1122
AbstractThe two recently collected mammalian dentary fragments from the Eocene Youganwo Formation of Guangdong Province, southern China, are referred to the anthracotheriid species Anthracokeryx naduongensis based on phylogenetic analysis and size comparison. One of these specimens (SYSU-M-1) is the first mammal fossil described from the Youganwo Formation. It was attributed previously to the perissodactyl genus Lunania. Anthracokeryx naduongensis was described originally from the lower upper Eocene Na Duong Formation in Northern Vietnam. The second record of this species supports a basal upper Eocene correlation for the Youganwo Formation, which was estimated previously as middle or late Eocene. 相似文献