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81.
Dyson A Bryan NS Fernandez BO Garcia-Saura MF Saijo F Mongardon N Rodriguez J Singer M Feelisch M 《Free radical biology & medicine》2011,51(6):1137-1145
Most studies examining the metabolic fate of NO during systemic inflammation have focused on measuring the quantitatively predominating, stable anions nitrite and nitrate within the circulation. However, these are not necessarily the NO-related products that govern NO metabolism and signaling in tissues. We assessed all major NO derivatives temporally in blood and vital organs during inflammation and explored their relationship to insult severity and redox status. Male rats receiving intraperitoneal endotoxin or vehicle were sacrificed for organ and blood sampling between 0 and 24 h. Endotoxin induced transient and organ-specific changes in a variety of NO metabolites. Nitrite and nitrate increased, peaking at 8 and 12 h, respectively. S- and N-nitrosation and heme-nitrosylation products also peaked at 8 h; these posttranslational protein modifications were associated with decreased myocardial function (echocardiography). Evidence of oxidative stress and systemic inflammation was also obtained. The rise in most NO derivatives was proportional to insult severity. All metabolite levels normalized within 24 h, despite evidence of persisting myocardial dysfunction and clinical unwellness. Our findings point to a complex interplay between NO production, antioxidant defense, and redox status. Although the precise (patho)physiologic roles of specific NO derivatives and their diagnostic/prognostic utility await further investigation, nitroso species in erythrocytes are the most sensitive markers of NO in systemic inflammation, detectable before clinical symptoms manifest. 相似文献
82.
Aweda TA Eskandari V Kukis DL Boucher DL Marquez BV Beck HE Mitchell GS Cherry SR Meares CF 《Bioconjugate chemistry》2011,22(8):1479-1483
We describe the synthesis and development of new reactive DOTA-metal complexes for covalently targeting engineered receptors in vivo, which have superior tumor uptake and clearance properties for biomedical applications. These probes are found to clear efficiently through the kidneys and minimally through other routes, but bind persistently in the tumor target. We also explore the new technique of Cerenkov luminescence imaging to optically monitor radiolabeled probe distribution and kinetics in vivo. Cerenkov luminescence imaging uniquely enables sensitive noninvasive in vivo imaging of a β(-) emitter such as (90)Y with an optical imager. 相似文献
83.
Arnaud Foulquier Florian Mermillod-Blondin Bernard Montuelle Sylvain Dolédec Bernadette Volat Janine Gibert 《Ecosystems》2011,14(8):1339-1353
Groundwaters are increasingly viewed as resource-limited ecosystems in which fluxes of dissolved organic carbon (DOC) from
surface water are efficiently mineralized by a consortium of microorganisms which are grazed by invertebrates. We tested for
the effect of groundwater recharge on resource supply and trophic interactions by measuring physico-chemistry, microbial activity
and biomass, structure of bacterial communities and invertebrate density at three sites intensively recharged with surface
water. Comparison of measurements made in recharge and control well clusters at each site showed that groundwater recharge
significantly increased fluxes of DOC and phosphate, elevated groundwater temperature, and diminished dissolved oxygen (DO).
Microbial biomass and activity were significantly higher in recharge well clusters but stimulation of autochthonous microorganisms
was not associated with a major shift in bacterial community structure. Invertebrate assemblages were not significantly more
abundant in recharge well clusters and did not show any relationship with microbial biomass and activity. Microbial communities
were bottom-up regulated by DOC and nutrient fluxes but trophic interactions between microorganisms and invertebrates were
apparently limited by environmental stresses, particularly DO depletion and groundwater warming. Hydrological connectivity
is a key factor regulating the function of DOC-based groundwater food webs as it influences both resource availability for
microorganisms and environmental stresses which affect energy transfer to invertebrates and top-down control on microorganisms. 相似文献
84.
85.
Chasseigneaux S Dinc L Rose C Chabret C Coulpier F Topilko P Mauger G Allinquant B 《PloS one》2011,6(1):e16301
Background
sAPPα released after α secretase cleavage of Amyloid Precursor Protein (APP) has several functions including the stimulation of neurite outgrowth although detailed morphometric analysis has not been done. Two domains involved in this function have been described and are present in sAPPβ released at the first step of amyloid peptide cleavage, raising the possibility that sAPPβ could also stimulate neurite outgrowth. We investigated the morphological effects of sAPPα and sAPPβ on primary neurons and identified a key signaling event required for the changes observed.Methodology/Principal Findings
Final concentrations of 50 to 150 nM bacterial recombinant sAPPα or sAPPβ added to primary neuronal cultures after 1 day in vitro decreased cell adhesion 24 hours later and primary dendrite length 96 hours later. 150 nM sAPPα and sAPPβ induced a similar increase of axon outgrowth, although this increase was already significant at 100 nM sAPPα. These morphological changes induced by sAPPs were also observed when added to differentiated neurons at 5 days in vitro. Real time PCR and immunocytochemistry showed that sAPPα and sAPPβ stimulated Egr1 expression downstream of MAPK/ERK activation. Furthermore, in primary neurons from Egr1 −/− mice, sAPPs affected dendritic length but did not induce any increase of axon length.Conclusion/Significance
sAPPα and sAPPβ decrease cell adhesion and increase axon elongation. These morphological changes are similar to what has been observed in response to heparan sulfate. The sAPPα/sAPPβ stimulated increase in axon growth requires Egr1 signaling. These data suggest that sAPPβ is not deleterious per se. Since sAPPβ and sAPPα are present in the embryonic brain, these two APP metabolites might play a role in axon outgrowth during development and in response to brain damage. 相似文献86.
Nwaka S Besson D Ramirez B Maes L Matheeussen A Bickle Q Mansour NR Yousif F Townson S Gokool S Cho-Ngwa F Samje M Misra-Bhattacharya S Murthy PK Fakorede F Paris JM Yeates C Ridley R Van Voorhis WC Geary T 《PLoS neglected tropical diseases》2011,5(12):e1412
New chemical entities are desperately needed that overcome the limitations of existing drugs for neglected diseases. Screening a diverse library of 10,000 drug-like compounds against 7 neglected disease pathogens resulted in an integrated dataset of 744 hits. We discuss the prioritization of these hits for each pathogen and the strong correlation observed between compounds active against more than two pathogens and mammalian cell toxicity. Our work suggests that the efficiency of early drug discovery for neglected diseases can be enhanced through a collaborative, multi-pathogen approach. 相似文献
87.
The recent development of transgenic mosquitoes that are resistant to infection by the Plasmodium malarial parasite is a promising new tool in the fight against malaria. However, results of large-scale field releases of alternatively modified mosquitoes carried out during the 1970s and 1980s suggest that this approach could be difficult to implement in the field. These past attempts to control mosquito populations largely floundered as a result of our insufficient understanding of the behavioural ecology of released males. In spite of this, contemporary research on genetic control strategies has concentrated predominantly on molecular aspects, with little progress being made toward resolving key ecological uncertainties, male mosquito ecology being the most important. Here, we review the state of knowledge of male mosquito ecology, and highlight priorities for further research. Case studies of two crop pests, the Mediterranean fruit fly and melon fly, are given as examples of how knowledge of male ecology facilitates successful control in other species. Unless similar information becomes available for mosquitoes, any future genetic control strategy will risk failure. 相似文献
88.
Viral protein VP4 is a target of human antibodies enhancing coxsackievirus B4- and B3-induced synthesis of alpha interferon
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Chehadeh W Lobert PE Sauter P Goffard A Lucas B Weill J Vantyghem MC Alm G Pigny P Hober D 《Journal of virology》2005,79(22):13882-13891
Coxsackievirus B4 (CVB4)-induced production of alpha interferon (IFN-alpha) by peripheral blood mononuclear cells (PBMC) is enhanced in vitro by nonneutralizing anti-CVB4 antibodies from healthy subjects and, to a higher extent, from patients with insulin-dependent diabetes mellitus. In this study, we focused on identification of the viral target of these antibodies in CVB systems. High levels of IFN-alpha were obtained in supernatants of PBMC incubated with CVB4E2 or CVB3 and plasma from healthy subjects and, to a higher extent, from patients. The VP4 capsid proteins dissociated by heating at 56 degrees C from CVB4E2 (VP4(CVB4)) and CVB3 (VP4(CVB3)) but not H antigen preincubated with plasma from healthy subjects or patients inhibited the plasma-dependent enhancement of CVB4E2- and CVB3-induced IFN-alpha synthesis. There was no cross-reaction between VP4(CVB4) and VP4(CVB3) in the inhibiting effect. IFN-alpha levels in culture supernatants showed dose-dependent correlation with anti-VP4 antibodies eluted from plasma specimens using VP4-coated plates. There were higher index values for anti-VP4 antibodies detected by enzyme-linked immunosorbent assay (ELISA) and higher proportions of positive detection in 40 patients than in 40 healthy subjects (80% versus 15% for anti-VP4(CVB4)). There was no relationship between the levels of anti-CVB neutralizing antibodies and the detection of anti-VP4 antibodies by ELISA. The CVB plasma-induced IFN-alpha levels obtained in PBMC cultures in the anti-VP4 antibody-positive groups were significantly higher than those obtained in the anti-VP4 antibody-negative groups regardless of the titers of anti-CVB neutralizing antibodies. These results show that VP4 is the target of antibodies involved in the plasma-dependent enhancement of CVB4E2- and CVB3-induced IFN-alpha synthesis by PBMC. 相似文献
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90.