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91.
This article focuses on ageing in transnationalism. Drawing on the experiences of Italians in the UK as a paradigmatic example of settled European migrants, it explores the lived experiences of this group of older migrants. Using Levitt and Glick Schiller's framework, it concentrates first on migrants' ways of being and then on their ways of belonging. The article argues that a transnational lens is necessary to understand the experiences of older migrants and that a focus on older people needs to be incorporated into studies of transnationalism. Through a discussion of their narratives and experiences, the article offers a long view on the migration process and brings attention to the significance of gender, time and the life course to understand both migrants' transnationalism and their integration.  相似文献   
92.
One unresolved issue in geomicrobiology is the involvement of microbial activity in the formation of secondary mineral deposits, or speleothems, in caves. Although there is extensive literature demonstrating the importance of bacteria in the precipitation of calcite in noncave environments, the role that these organisms play within caves remains unclear. Evidence in support of microbial involvement in deposition of speleothems has often not been compelling. Following the "Rules for the Hunt" first proposed by Schopf and Walter to determine whether structures in rock were biogenic in origin, we propose a similar set of guidelines for evaluation of microbial association with cave features. We also illustrate methods that may help unravel the complex problem of microorganism involvement in secondary mineral deposition in caves.  相似文献   
93.
Intellectual disability in Down syndrome (DS) appears to be related to severe proliferation impairment during brain development. Recent evidence shows that it is not only cellular proliferation that is heavily compromised in DS, but also cell fate specification and dendritic maturation. The amyloid precursor protein (APP), a gene that is triplicated in DS, plays a key role in normal brain development by influencing neural precursor cell proliferation, cell fate specification, and neuronal maturation. APP influences these processes via two separate domains, the APP intracellular domain (AICD) and the soluble secreted APP. We recently found that the proliferation impairment of neuronal precursors (NPCs) from the Ts65Dn mouse model for DS was caused by derangement of the Shh pathway due to overexpression of patched1(Ptch1), its inhibitory regulator. Ptch1 overexpression was related to increased levels within the APP/AICD system. The overall goal of this study was to determine whether APP contributes to neurogenesis impairment in DS by influencing in addition to proliferation, cell fate specification, and neurite development. We found that normalization of APP expression restored the reduced neuronogenesis, the increased astrogliogenesis, and the reduced neurite length of trisomic NPCs, indicating that APP overexpression underpins all aspects of neurogenesis impairment. Moreover, we found that two different domains of APP impair neuronal differentiation and maturation in trisomic NPCs. The APP/AICD system regulates neuronogenesis and neurite length through the Shh pathway, whereas the APP/secreted AP system promotes astrogliogenesis through an IL-6-associated signaling cascade. These results provide novel insight into the mechanisms underlying brain development alterations in DS.  相似文献   
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Chondroitin sulfate is a well-known bioactive molecule, widely used as an anti-osteoarthritis drug, that is nowadays mainly produced by animal tissue sources with unsafe extraction procedures. Recent studies have explored an integrated biotechnological–chemical strategy to obtain a chondroitin sulfate precursor from Escherichia coli K4 capsular polysaccharide, demonstrating the influence of environmental and growth conditions on capsule synthesis. In this research work, the flexibility of the strain biosynthetic machinery was investigated to enhance the K4 capsular polysaccharide production by supplementing the growth medium with the monosaccharides (glucuronic acid, galactosamine and fructose) that constitute the chain. Shake flask experiments were performed by adding the sugars singularly or together, by testing monosaccharide different concentrations and times of addition and by observing the bacterial sugar consumption. A K4 capsular polysaccharide production enhancement, compared to the control, was observed in all cases of supplementation and, in particular, significant 68 and 57 % increases were observed when adding 0.385 mM glucuronic acid plus galactosamine or 0.385 mM fructose, respectively. Increased expression levels of the gene kfoC, coding for a K4 polymerase, evaluated in different growth conditions, confirmed the results at the molecular level. Furthermore, batch fermentations, performed in lab-scale reactors (2 L), allowed to double the K4 capsular polysaccharide production values obtained in shake flask conditions, by means of a strict control of the growth parameters.  相似文献   
97.
A study was carried out to investigate the influence of atmospheric pollen and fungi in determining allergic diseases by comparing the frequency of skin reactions to air sampling data over a 6-year period.

48% of our population reacted to at least one of the pollen and fungal extracts used. Among pollen, Gramineae gave the most frequent positive reactions, followed by Parietaria, Olea and Compositae. The most common positive skin tests in fungus sensitive patients were by extracts of Alternaria, Cladosporium, Aspergillus and Candida

As for the aerobiological survey, the general trend of pollen and molds was similar during the sampling period. The annual pollen catch did not show remarkable differences during the years sampled, whereas the total fungal spore count was highest in 1988 and 1990.

A comparison between aerobiological and clinical data revealed a good degree of concordance between total pollen counts and positive skin test frequencies for Urticaceae, Gramineae and Oleaceae but not for Compositae (high positive skin reactions and very low counts) and Cupressaceae (high counts and few skin reactions).

A less marked correlation has been found between fungal spore counts and positive skin-test frequencies as compared to pollen. Spores such as Cladosporium, which are present in large number in the air, appear to be less sensitizing, while certain spore types (e.g. Alternaria), seem to be able to sensitize patients in spite of their low atmospheric concentrations.  相似文献   
98.
We report the synthesis and bio-pharmacological evaluation of a class of pyrrole derivatives featuring a small appendage fragment (carbaldehyde, oxime, nitrile) on the central core. Compound 1c proved to be extremely effective in vivo, showing an interesting anti-nociceptic profile that is comparable to reference compounds already marketed, hence representing a great stimulus for a further improvement of this class of molecules.  相似文献   
99.
As a continuation of previous research on a new series of potent and efficacious P-gp-dependent multidrug resistant (MDR) reversers with a N,N-bis(cyclohexanol)amine scaffold, we have designed and synthesized several analogs by modulation of the two aromatic moieties linked through ester functions to the N,N-bis(cyclohexanol)amine, aiming to optimize activity and to extend structure–activity relationships (SAR) within the series. This scaffold, when esterified with two different aromatic carboxylic acids, gives origin to four geometric isomers (cis/trans, trans/trans, cis/cis and trans/cis).The new compounds were tested on doxorubicin-resistant erythroleukemia K562 cells (K562/DOX) in the pirarubicin uptake assay. Most of them resulted in being potent modulators of the extrusion pump P-gp, showing potency values ([I]0.5) in the submicromolar and nanomolar range. Of these, compounds 2b, 2c, 3d, 5ad and 6d, showed excellent efficacy with a αmax close to 1. Selected compounds (2d, 3a, 3b, 5ad) were further studied to evaluate their doxorubicin cytotoxicity potentiation (RF) on doxorubicin-resistant erythroleukemia K562 cells and were found able to enhance significantly doxorubicin cytotoxicity on K562/DOX cells.The results of both pirarubicin uptake and the cytotoxicity assay, indicate that the new compounds of the series are potent P-gp-mediated MDR reversers. They present a structure with a mix of flexible and rigid moieties, a property that seems critical to allow the molecules to choose the most productive of the several binding modes possible in the transporter recognition site.In particular, compounds 5c and 5d, similar to the already reported analogous isomers 1c and 1d,29 are potent and efficacious modulators of P-gp-dependent MDR and may be promising leads for the development of MDR-reversal drugs.  相似文献   
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