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21.
Fecal glucocorticoid metabolites and assay validation: Stress response evaluation in captive brown howler monkeys (Alouatta clamitans)
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22.
The underlying mechanisms of acetylcholine-induced intestinal relaxation in the lizard Liolaemus tenuis tenuis are still unknown. By using a classical model of intestinal recording of isometric contraction and relaxation in conjunction with specific pharmacological tools, this article studies the possible influence of EDRF/NO and nicotinic ganglionar receptors on the Ach-induced relaxation in an effort to elucidate the probable mechanisms involved in ACh effect. It was observed that the relaxation of the lizard intestine elicited by ACh (10(-7) - 4 x 10(-4) M) was not affected by hexametonium (5 x 10(-4) M) or tetrodotoxin (10(-6) M). Nicotine (10(-7) to 10(-4) M) induced relaxation was significantly antagonized by hexametonium; however, it was not influenced by tetrodotoxin. These results allow us to discard a neuronal pathway in cholinergic-induced relaxation, suggesting a more direct cholinergic effect on the smooth muscle, perhaps mediated by an unknown substance released by some specialized tissue. N-nitro-L-arginine, used to block NO-synthase and NO production, induced no changes in ACh-induced relaxation. Methylene blue, a soluble guanylate cyclase inhibitor, induced no changes in ACh-induced relaxation. These results allow us to discard a probable role of EDRF/nitric oxide in the ACh-induced relaxation of lizard small intestine, providing evidence that this mechanism could be different from that reported in other species. 相似文献
23.
Isotopic analyses of the incrementally growing baleen in Mysticeti have been used to learn about their feeding and movement patterns. Using methods previously applied to Pacific minke whales, stable δ15N and δ13C isotope values were measured along the baleen plates of male and female minke whales from two locations in the Northeast Atlantic. The sample sizes used in this study are comparable to those previously used in the literature, and, although limited in size, the evidence suggests differences in isotopic signatures between whales caught at different locations. Both the δ15N and δ13C data suggest whales at the higher latitude site of Svalbard have a narrower diet than the whales from Lofoten/Vesterålen in Norway. Across all whales, the δ15N data indicate the whales primarily prey on fish for much of the year, only switching to zooplankton during the spring bloom. The δ13C data fail to confirm whether the whales migrate over long distances. 相似文献
24.
The cellular distribution and changes of sugar residues during tooth development in embryos of the rabbit Oryctolagus cuniculus were investigated by using horseradish peroxidase-conjugated lectins (lectin-HRP). The lectins SBA, ECA, and LTA show no binding to any region of the dental cap and bell stages, whereas BS-1 and UEA-1 bind to dental cells at both stages. Appropriate control studies confirmed the specificity of the binding of the lectins. At cap stage, the lectins BS-1 and UEA-1 show moderate binding to the (pre)-ameloblast and (pre)-odontoblast cells. These results suggest that the acetylgalactosamine and α-L-fucose residues present in (pre)-ameloblasts and (pre)-odontoblasts, respectively, are common to determined but relatively undifferentiated cells capable of forming matrices of hard tissues. Since the odontoblast and ameloblast express dentin and enamel, respectively, it can be speculated that the abundance of these residues in these cells might be associated with the maintenance of the capacity of the cells to produce such matrices. At the bell stage, the odontoblasts display considerable amounts of α-L-fucose, whereas α-L-fucose is poorly localized in ameloblasts. However, ameloblasts contain significant quantities of N-acetylgalactosamine, whereas only a diffuse positivity for this carbohydrate is apparent in odontoblasts. The marked changes of the glycosylation pattern of these glycoconjugates might indicate that they play a role during the cell-to-cell interaction and might also be involved in the odontoblastic and ameloblastic functional activity. Such a possibility is entirely speculative until specific in vitro experiments are conducted. J. Morphol. 231:175–184, 1997. © 1997 Wiley-Liss, Inc. 相似文献
25.
Asymmetric paternal effect on offspring size linked to parent‐of‐origin expression of an insulin‐like growth factor
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Yolitzi Saldivar Lemus Jean‐Philippe Vielle‐Calzada Michael G. Ritchie Constantino Macías Garcia 《Ecology and evolution》2017,7(12):4465-4474
Sexual reproduction brings together reproductive partners whose long‐term interests often differ, raising the possibility of conflict over their reproductive investment. Males that enhance maternal investment in their offspring gain fitness benefits, even if this compromises future reproductive investment by iteroparous females. When the conflict occurs at a genomic level, it may be uncovered by crossing divergent populations, as a mismatch in the coevolved patterns of paternal manipulation and maternal resistance may generate asymmetric embryonic growth. We report such an asymmetry in reciprocal crosses between populations of the fish Girardinichthys multiradiatus. We also show that a fragment of a gene which can influence embryonic growth (Insulin‐Like Growth Factor 2; igf2) exhibits a parent‐of‐origin methylation pattern, where the maternally inherited igf2 allele has much more 5′ cytosine methylation than the paternally inherited allele. Our findings suggest that male manipulation of maternal investment may have evolved in fish, while the parent‐of‐origin methylation pattern appears to be a potential candidate mechanism modulating this antagonistic coevolution process. However, disruption of other coadaptive processes cannot be ruled out, as these can lead to similar effects as conflict. 相似文献
26.
Field studies were conducted in 2000 and 2001 to examine yields and nutrient removal by Alamo switchgrass (Panicum virgatum L.) grown at eight locations within five states in the upper southeastern USA. Plots, which had been established for >5 years as part of a larger study, were cut either once (late fall) or twice (midsummer and late fall). Plots cut once received 50 kg N per hectare per year, while twice-cut plots received 100 kg N per hectare per year. Nutrient concentrations of and nutrient removal by harvested biomass were determined. Partitioning of nutrients into leaf and stem fractions was determined at the time of the midsummer harvest in 2000. Biomass production during 2000 and 2001 averaged 15.9 Mg/ha per year across all sites and was as high as 21.7 Mg/ha per year at one site. Two cuttings plus the additional 50 kg N per hectare did not generally increase seasonal yields; and, in one quite productive location, that management caused a yield reduction. Nitrogen removal with two cuts was much higher than with a single cut due largely to the higher N content in the midsummer harvest. Over the 2 years, twice as much N was removed with the two annual cuts as with one cut. Nitrogen removal exceeded the amounts of N applied in both managements, suggesting N was being supplied via mineralization or other processes. Phosphorus removal also increased significantly with the two-cut management. Seasonal K and Ca removals were more similar between the two managements. Nitrogen and P concentrations generally declined basipetally in tillers, with older leaves and internodes having lower concentrations of both nutrients. Potassium was more uniformly distributed than N throughout the tiller components (leaf and stem). Calcium was higher in older leaf blades. Levels of soil P, K, and Ca at most locations appeared not to be limiting biomass production and were adequate for long-term productivity. 相似文献
27.
Biodistribution of a Bispecific Single-chain Diabody and Its Half-life Extended Derivatives 总被引:1,自引:0,他引:1
Roland Stork Emmanuelle Campigna Bruno Robert Dafne M��ller Roland E. Kontermann 《The Journal of biological chemistry》2009,284(38):25612-25619
Small recombinant antibody molecules such as bispecific single-chain diabodies (scDb) possessing a molecular mass of ∼55 kDa are rapidly cleared from circulation. We have recently extended the plasma half-life of scDb applying various strategies including PEGylation, N-glycosylation and fusion to an albumin-binding domain (ABD) from streptococcal protein G. Here, we further analyzed the influence of these modifications on the biodistribution of a scDb directed against carcinoembryonic antigen (CEA) and CD3 capable of retargeting T cells to CEA-expressing tumor cells. We show that a prolonged circulation time results in an increased accumulation in CEA+ tumors, which was most pronounced for scDb-ABD and PEGylated scDb. Interestingly, tumor accumulation of the scDb-ABD fusion protein was ∼2-fold higher compared with PEGylated scDb, although both molecules exhibit similar plasma half-lives and similar affinities for CEA. Comparing half-lives in neonatal Fc receptor (FcRn) wild-type and FcRn heavy chain knock-out mice the contribution of the FcRn to the long plasma half-life of scDb-ABD was confirmed. The half-life of scDb-ABD was ∼2-fold lower in the knock-out mice, while no differences were observed for PEGylated scDb. Binding of the scDb derivatives to target and effector cells was not or only marginally affected by the modifications, although, compared with scDb, a reduced cytotoxic activity was observed for scDb-ABD, which was further reduced in the presence of albumin. In summary, these findings demonstrate that the extended half-life of a bispecific scDb translates into improved accumulation in antigen-positive tumors but that modifications might also affect scDb-mediated cytotoxicity.Bispecific single-chain diabodies (scDb)2 are recombinant molecules composed of the variable heavy and light chain domains of two antibodies connected by three linkers in the order VHA-VLB-VHB-VLA (1). These domains assemble into molecules with a compact structure and molecular masses of ∼55 kDa. Bispecific single-chain diabodies have been developed for various applications including the retargeting of cytotoxic T lymphocytes to tumor cells for cellular cancer therapy (2).Although scDb are capable of efficiently retargeting effector cells to tumor cells the small size leads to their rapid elimination after i.v. injection. The terminal half-life of these molecules in mice is only in the range of 5–6 h, compared with several days for whole IgG molecules (3, 4). The fast clearance of such small molecules from circulation hampers therapeutic applications, e.g. requiring infusions or repeated injections to maintain a therapeutically effective dose over a prolonged period of time (5). For example, a bispecific tandem scFv directed against CD19 and CD3 (blinatumomab) having a similar size as an scDb molecule had to be given as an 8-week infusion (maximum dose 60 μg/m2 per day) in a clinical phase I trial for the treatment of B cell lymphoma patients (6).To extend plasma half-lives of therapeutic proteins and thus to improve pharmacokinetics and pharmacodynamics, several strategies can be applied (7). Strategies such as conjugation of polyethylene glycol chains (PEGylation) or production of hyperglycosylated variants through introduction of additional N-glycosylation sites primarily aim at increasing the hydrodynamic volume of the molecule, thus reducing renal filtration and degradation. Some of these strategies further implement FcRn-mediated recycling processes, e.g. fusion to the IgG Fc region and fusion or binding to serum albumin.We recently applied several of these strategies to improve the plasma half-life of a scDb molecule. These strategies included site-directed conjugation of a 40-kDa PEG chain (PEGylated scDb, scDb-A′-PEG40k), production of N-glycosylated scDb variants possessing 3, 6, or 9 N-glycosylation sites (scDb-ABC1–7), a scDb-human serum albumin fusion protein (scDb-HSA), and a scDb fused to an albumin-binding domain from streptococcal protein G (scDb-ABD) (3, 4, 8). In these studies we showed that N-glycosylation only moderately increased half-life, while a strong improvement was observed for the PEGylated scDb, scDb-HSA, and scDb-ABD.In the present study we further analyzed the biodistribution of unmodified scDb as well as three of the scDb derivatives (PEGylated scDb, N-glycosylated scDb, scDb-ABD) in tumor-bearing mice. We show that the modified scDb molecules exhibit a reduced renal clearance and that an extended half-life leads to an increased accumulation in antigen-positive tumors. The strongest improvement was observed for scDb-ABD. Using FcRn knock-out mice we confirmed that FcRn-mediated recycling contributes to the long half-life of scDb-ABD. Affinities of the scDb derivatives for target and effector cells were not or only marginally affected by the modifications, although, compared with scDb, a reduced cytotoxic activity was observed for scDb-ABD, which was further reduced in the presence of albumin. These findings demonstrate that half-life extension of scDb results in increased tumor accumulation but that modifications might also affect scDb-mediated cytotoxicity. 相似文献
28.
Morales M Arancibia J Lemus M Silva J Gentina JC Aroca G 《Biotechnology letters》2011,33(11):2141-2145
Sulfolobus metallicus is a hyperthermophilic and chemolithoautotrophic archaeon that uses elemental sulfur as an energy source. Its ability to
oxidize H2S was measured either in the presence or absence of elemental sulphur, showing its ability for using both as an energy source.
A biotrickling filter was set up and a biofilm of S. metallicus was established over the support. The maximum removal capacity of the biotrickling filter reached at 55°C was 40 g S/m3h for input loads higher than 70 g S/m3h. Thus, S. metallicus can be used in a biofiltration system for the treatment of waste gas emissions at high temperatures contaminated with H2S. 相似文献
29.
Misol Ahn Krystyna Bajsarowicz Abby Oehler Azucena Lemus Krystof Bankiewicz Stephen J. DeArmond 《PloS one》2014,9(5)
Prion disease is caused by a single pathogenic protein (PrPSc), an abnormal conformer of the normal cellular prion protein PrPC. Depletion of PrPC in prion knockout mice makes them resistant to prion disease. Thus, gene silencing of the Prnp gene is a promising effective therapeutic approach. Here, we examined adeno-associated virus vector type 2 encoding a short hairpin RNA targeting Prnp mRNA (AAV2-PrP-shRNA) to suppress PrPC expression both in vitro and in vivo. AAV2-PrP-shRNA treatment suppressed PrP levels and prevented dendritic degeneration in RML-infected brain aggregate cultures. Infusion of AAV2-PrP-shRNA-eGFP into the thalamus of CD-1 mice showed that eGFP was transported to the cerebral cortex via anterograde transport and the overall PrPC levels were reduced by ∼70% within 4 weeks. For therapeutic purposes, we treated RML-infected CD-1 mice with AAV2-PrP-shRNA beginning at 50 days post inoculation. Although AAV2-PrP-shRNA focally suppressed PrPSc formation in the thalamic infusion site by ∼75%, it did not suppress PrPSc formation efficiently in other regions of the brain. Survival of mice was not extended compared to the untreated controls. Global suppression of PrPC in the brain is required for successful therapy of prion diseases. 相似文献
30.
Alberto Jiménez-Maldonado Elena Roces de álvarez-Buylla Sergio Montero Valery Melnikov Elena Castro-Rodríguez Armando Gamboa-Domínguez Alejandrina Rodríguez-Hernández Mónica Lemus Jesús Mu?iz Murguía 《PloS one》2014,9(12)