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排序方式: 共有117条查询结果,搜索用时 31 毫秒
11.
Vacca F D'Ambrosi N Nestola V Amadio S Giustizieri M Cucchiaroni ML Tozzi A Velluz MC Mercuri NB Volonté C 《Glycobiology》2011,21(5):634-643
N-Glycosylation affects the function of ion channels at the level of multisubunit assembly, protein trafficking, ligand binding and channel opening. Like the majority of membrane proteins, ionotropic P2X receptors for extracellular ATP are glycosylated in their extracellular moiety. Here, we used site-directed mutagenesis to the four predicted N-glycosylation sites of P2X(3) receptor (Asn(139), Asn(170), Asn(194) and Asn(290)) and performed comparative analysis of the role of N-glycans on protein stability, plasma membrane delivery, trimer formation and inward currents. We have found that in transiently transfected HEK293 cells, Asn(170) is apparently the most important site for receptor stability, since its mutation causes a primary loss in protein content and indirect failure in membrane expression, oligomeric association and inward current responses. Even stronger effects are obtained when mutating Thr(172) in the same glycosylation consensus. Asn(194) and Asn(290) are the most dispensable, since even their simultaneous mutation does not affect any tested receptor feature. All double mutants containing Asn(170) mutation or the Asn(139)/Asn(290) double mutant are instead almost unable to assemble into a functional trimeric structure. The main emerging finding is that the inability to assemble into trimers might account for the impaired function in P2X(3) mutants where residue Asn(170) is replaced. These results improve our knowledge about the role of N-glycosylation in proper folding and oligomeric association of P2X(3) receptor. 相似文献
12.
A structural transition is reported to occur in aqueous sols of agarose, an electrically uncharged biostructural polysaccharide. The transition has no measurable effect on size dispersity on the shape of the solute polysaccharide as observed by precision photon correlation spectroscopy. It originates a low-angle pattern of scattered light similar to that which monitors phase separations in polymer blends. Thus, it must be due to some extent to spatially modulated polymer clustering, typical of spinodal decomposition. In the interval of temperatures studied, it precedes very distinctly in time the thermoreversible sol–gel transition, which is known to be promoted at higher concentrations. It also anticipates to an appreciable extent the spatial density modulation observed in the gel. Although reported here for the first time, a spinodal decomposition of the sol that precedes and possibly triggers the processes leading to gelation does not come unexpectedly in terms of site-bond correlated-percolation theory. In general, this occurrence raises the question as to whether the spontaneous onset of regions of higher and lower polymer concentration (spinodal separation) may be regarded as a novel path for biomolecular interactions and the self-assembly of order in biomolecular systems. 相似文献
13.
Kinetics of insulin aggregation: disentanglement of amyloid fibrillation from large-size cluster formation 下载免费PDF全文
Kinetics of human insulin aggregation has been studied at pH 1.6 and 60 degrees C, when amyloid fibrils are formed. We developed a novel approach based on the analysis of scattered light intensity distribution, which allows distinguishing between small and large size aggregates. By this method, we observed an exponential growth of fibrillar aggregates implying a heterogeneous aggregation mechanism. Also, the apparent lag time observed, correlated with the major increase of thioflavin T fluorescence, has been assigned to the onset of large size cluster formation. 相似文献
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15.
In 23 cases of carcinoma of the head and neck, the combined use of Somatostatin and/or its analogue Octreotide, prolactin inhibitors, Melatonin, Retinoids, Vitamin E, Vitamin D3, Vitamin C, Calcium, chondroitin-sulphate, and minimal oral doses of cyclophosphamide (50-100 mg/day) led to a decided increase in survival with respect to the median values reported in the literature for the same tumours and stages, together with an evident improvement in the quality of life, partial or complete objective responses and, in some cases, complete and stable cure with functional recovery. The rationale and the mechanisms of molecular biology of the treatment are discussed, showing that the treatment has a differentiating, apoptotic, antiproliferative, antiangiogenic and antimetastatic effect, and, unlike chemo- and/or radiotherapy, preserves and enhances the trophism and functionality of organs, tissues and immunitary and antitumoral homeostasis. This result, achieved without toxicity, demonstrates the efficacy of this biological multitherapy (Prof. Luigi Di Bella's method or DBM) and is in agreement with the positive results already published on the use of the DBM in various neoplastic diseases. We believe it is of use to report these cases to invite greater interest in the possibilities opened up by this biological multitherapy. 相似文献
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Hoffecker JF Holliday VT Anikovich MV Sinitsyn AA Popov VV Lisitsyn SN Levkovskaya GM Pospelova GA Forman SL Giaccio B 《Journal of human evolution》2008,55(5):858-870
The Campanian Ignimbrite (CI) eruption, dated by 40Ar/39Ar and various stratigraphic methods to ca. 39,000 cal BP, generated a massive ash plume from its source in southern Italy across Southeastern and Eastern Europe. At the Kostenki-Borshchevo open-air sites on the Middle Don River in Russia, Upper Paleolithic artifact assemblages are buried below, within, and above the CI tephra (which is redeposited by slope action at most sites) on the second terrace. Luminescence and radiocarbon dating, paleomagnetism, and soil and pollen stratigraphy provide further basis for correlation with the Greenland and North Atlantic climate stratigraphy. The oldest Upper Paleolithic occupation layers at Kostenki-Borshchevo may be broadly correlated with warm intervals that preceded the CI event and Heinrich Event 4 (HE4; Greenland Interstadial: GI 12-GI 9) dating to ca. 45,000-41,000 cal BP. These layers contain an industry not currently recognized in other parts of Europe. Early Upper Paleolithic layers above the CI tephra are correlated with HE4 and warm intervals that occurred during 38,000-30,000 cal BP (GI 8-GI 5), and include an assemblage that is assigned to the Aurigancian industry, associated with skeletal remains of modern humans. 相似文献
18.
Federica Bozzano Chiara Dentone Carola Perrone Antonio Di Biagio Daniela Fenoglio Alessia Parodi Malgorzata Mikulska Bianca Bruzzone Daniele Roberto Giacobbe Antonio Vena Lucia Taramasso Laura Nicolini Nicol Patroniti Paolo Pelosi Angelo Gratarola Raffaele De Palma Gilberto Filaci Matteo Bassetti Andrea De Maria 《PLoS pathogens》2021,17(4)
The SARS-CoV-2 infection causes severe respiratory involvement (COVID-19) in 5–20% of patients through initial immune derangement, followed by intense cytokine production and vascular leakage. Evidence of immune involvement point to the participation of T, B, and NK cells in the lack of control of virus replication leading to COVID-19. NK cells contribute to early phases of virus control and to the regulation of adaptive responses. The precise mechanism of NK cell dysregulation is poorly understood, with little information on tissue margination or turnover. We investigated these aspects by multiparameter flow cytometry in a cohort of 28 patients hospitalized with early COVID-19.Relevant decreases in CD56brightCD16+/- NK subsets were detected, with a shift of circulating NK cells toward more mature CD56dimCD16+KIR+NKG2A+ and “memory” KIR+CD57+CD85j+ cells with increased inhibitory NKG2A and KIR molecules. Impaired cytotoxicity and IFN-γ production were associated with conserved expression of natural cytotoxicity receptors and perforin. Moreover, intense NK cell activation with increased HLA-DR and CD69 expression was associated with the circulation of CD69+CD103+ CXCR6+ tissue-resident NK cells and of CD34+DNAM-1brightCXCR4+ inflammatory precursors to mature functional NK cells. Severe disease trajectories were directly associated with the proportion of CD34+DNAM-1brightCXCR4+ precursors and inversely associated with the proportion of NKG2D+ and of CD103+ NK cells.Intense NK cell activation and trafficking to and from tissues occurs early in COVID-19, and is associated with subsequent disease progression, providing an insight into the mechanism of clinical deterioration. Strategies to positively manipulate tissue-resident NK cell responses may provide advantages to future therapeutic and vaccine approaches. 相似文献
19.
Angela Pennacchio Assunta Giordano Biagio Pucci Mosè Rossi Carlo A. Raia 《Extremophiles : life under extreme conditions》2010,14(2):193-204
The gene encoding a novel alcohol dehydrogenase that belongs to the short-chain dehydrogenases/reductases (SDRs) superfamily
was identified in the aerobic thermoacidophilic crenarchaeon Sulfolobus acidocaldarius strain DSM 639. The saadh gene was heterologously overexpressed in Escherichia coli, and the protein (SaADH) was purified to homogeneity and characterized. SaADH is a tetrameric enzyme consisting of identical
28,978-Da subunits, each composed of 264 amino acids. The enzyme has remarkable thermophilicity and thermal stability, displaying
activity at temperatures up to 75°C and a 30-min half-inactivation temperature of ~90°C, and shows good tolerance to common
organic solvents. SaADH has a strict requirement for NAD(H) as the coenzyme, and displays a preference for the reduction of
alicyclic, bicyclic and aromatic ketones and α-keto esters, but is poorly active on aliphatic, cyclic and aromatic alcohols,
and shows no activity on aldehydes. The enzyme catalyses the reduction of α-methyl and α-ethyl benzoylformate, and methyl
o-chlorobenzoylformate with 100% conversion to methyl (S)-mandelate [17% enantiomeric excess (ee)], ethyl (R)-mandelate (50% ee), and methyl (R)-o-chloromandelate (72% ee), respectively, with an efficient in situ NADH-recycling system which involves glucose and a thermophilic
glucose dehydrogenase. This study provides further evidence supporting the critical role of the D37 residue in discriminating
NAD(H) from NAD(P)H in members of the SDR superfamily. 相似文献
20.
Antonella Marino Gammazza Manfredi Rizzo Roberto Citarrella Francesca Rappa Claudia Campanella Fabio Bucchieri Angelo Patti Dragana Nikolic Daniela Cabibi Giandomenico Amico Pier Giulio Conaldi Pier Luigi San Biagio Giuseppe Montalto Felicia Farina Giovanni Zummo Everly Conway de Macario Alberto J. L. Macario Francesco Cappello 《Cell stress & chaperones》2014,19(3):343-353
The role Hsp60 might play in various inflammatory and autoimmune diseases is under investigation, but little information exists pertaining to Hashimoto’s thyroiditis (HT). With the aim to fill this gap, in the present work, we directed our attention to Hsp60 participation in HT pathogenesis. We found Hsp60 levels increased in the blood of HT patients compared to controls. The chaperonin was immunolocalized in thyroid tissue specimens from patients with HT, both in thyrocytes and oncocytes (Hurthle cells) with higher levels compared to controls (goiter). In oncocytes, we found Hsp60 not only in the cytoplasm but also on the plasma membrane, as shown by double immunofluorescence performed on fine needle aspiration cytology. By bioinformatics, we found regions in the Hsp60 molecule with remarkable structural similarity with the thyroglobulin (TG) and thyroid peroxidase (TPO) molecules, which supports the notion that autoantibodies against TG and TPO are likely to recognize Hsp60 on the plasma membrane of oncocytes. This was also supported by data obtained by ELISA, showing that anti-TG and anti-TPO antibodies cross-react with human recombinant Hsp60. Antibody-antigen (Hsp60) reaction on the cell surface could very well mediate thyroid cell damage and destruction, perpetuating inflammation. Experiments with recombinant Hsp60 did not show stimulation of cytokine production by peripheral blood mononuclear cells from HT patients. All together, these results led us to hypothesize that Hsp60 may be an active player in HT pathogenesis via an antibody-mediated immune mechanism. 相似文献