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951.
952.
Iero M Squarcina P Romero P Guillaume P Scarselli E Cerino R Carrabba M Toutirais O Parmiani G Rivoltini L 《Cancer immunology, immunotherapy : CII》2007,56(12):1979-1991
The use of “altered peptide ligands” (APL), epitopes designed for exerting increased immunogenicity as compared with native
determinants, represents nowadays one of the most utilized strategies for overcoming immune tolerance to self-antigens and
boosting anti-tumor T cell-mediated immune responses. However, the actual ability of APL-primed T cells to cross-recognize
natural epitopes expressed by tumor cells remains a crucial concern. In the present study, we show that CAP1-6D, a superagonist
analogue of a carcinoembriyonic antigen (CEA)-derived HLA-A*0201-restricted epitope widely used in clinical setting, reproducibly
promotes the generation of low-affinity CD8+ T cells lacking the ability to recognized CEA-expressing colorectal carcinoma (CRC) cells. Short-term T cell cultures, obtained
by priming peripheral blood mononuclear cells from HLA-A*0201+ healthy donors or CRC patients with CAP1-6D, were indeed found to heterogeneously cross-react with saturating concentrations
of the native peptide CAP1, but to fail constantly lysing or recognizing through IFN- γ release CEA+CRC cells. Characterization of anti-CAP1-6D T cell avidity, gained through peptide titration, CD8-dependency assay, and staining
with mutated tetramers (D227K/T228A), revealed that anti-CAP1-6D T cells exerted a differential interaction with the two CEA
epitopes, i.e., displaying high affinity/CD8-independency toward the APL and low affinity/CD8-dependency toward the native
CAP1 peptide. Our data demonstrate that the efficient detection of self-antigen expressed by tumors could be a feature of
high avidity CD8-independent T cells, and underline the need for extensive analysis of tumor cross-recognition prior to any
clinical usage of APL as anti-cancer vaccines. 相似文献
953.
Dalila Serpa Manuela Falcão Pedro Duarte Luís Cancela da Fonseca Carlos Vale 《Biogeochemistry》2007,82(3):291-304
During an annual cycle, overlying water and sediment cores were collected simultaneously at three sites (Tavira, Culatra and
Ramalhete) of Ria Formosa’s intertidal muddy and subtidal sandy sediments to determine ammonium, nitrates plus nitrites and
phosphate. Organic carbon, nitrogen and phosphorus were also determined in superficial sediments. Ammonium and phosphate dissolved
in porewater were positively correlated with temperature (P < 0.01) in muddy and sandy sediments, while the nitrogen-oxidized forms had a negative correlation (P < 0.02) in muddy sediments probably because mineralization and nitrification/denitrification processes vary seasonally. Porewater
ammonium profiles evidenced a peak in the top-most muddy sediment (380 μM) suggesting higher mineralization rate when oxygen
is more available, while maximum phosphate concentration (113 μM) occurred in the sub-oxic layer probably due to phosphorus
desorption under reduced conditions. In organically poor subtidal sandy sediments, nutrient porewater concentrations were
always lower than in intertidal muddy sediments, ranging annually from 20 μM to 100 μM for ammonium and from 0.05 μM to 16 μM
for phosphate. Nutrient diffusive fluxes predicted by a mathematical model were higher during summer, in both muddy (104 nmol cm−2 d−1––NH4+; 8 nmol cm−2 d−1––HPO4−2) and sandy sediments (26 nmol cm−2 d−1––NH4+; 1 nmol cm−2 d−1––HPO4−2), while during lower temperature periods these fluxes were 3–4 times lower. Based on simulated nutrient effluxes, the estimated
annual amount of ammonium and phosphate exported from intertidal areas was three times higher than that released from subtidal
areas (22 ton year−1––NH4+; 2 ton year−1––HPO4−2), emphasizing the importance of tidal flats to maintain the high productivity of the lagoon. Global warming scenarios simulated
with the model, revealed that an increase in lagoon water temperature only produces significant variations (P < 0.05) for NH4+ in porewater and consequent diffusive fluxes, what will probably affect the system productivity due to a N/P ratio unbalance. 相似文献
954.
955.
Schreiber S Garten D Nguyen TH Konradt M Bücker R Scheid P 《Cell and tissue research》2007,329(2):313-320
The gastric H+/K+-ATPase is located within an infolding (secretory canaliculus) of the apical plasma membrane of gastric parietal cells. Our
aim was to measure the pH values in the cytosol and canaliculus of the acid-secreting parietal cell and the adjacent gland
lumen in situ. We used ultrafine double-barreled tip-sealed microelectrodes at high acceleration rates for intracellular and
canalicular measurements. Immunohistochemical staining of the parietal cells was used to identify the track of the electrode
and to estimate the position of the electrode tip at the time of the last intracellular measurement. En route to the deepest
regions of the mucosa, where the average gland lumen pH was approximately 3, and on advancing in steps of 2 μm, the electrode
entered the cytosol of the parietal cells, where the pH value was 7.4. Advancing the electrode further resulted, in several
instances, in a sharp decrease in pH to an average value of 1.7 ± 0.2, which we interpreted as the measurement within the
canaliculus. When the electrode was advanced even further, the pH reading returned to the cytosolic value. From the difference
in pH between the secreting canaliculus and the adjacent gland lumen, we concluded that the released acid was immediately
buffered. Thus, the only cellular structure directly exposed to the highly acidic canalicular content is the apical membrane
forming the canaliculus in the parietal cell. 相似文献
956.
A method allowing the evaluation of the structure and the calculation of the volume of a biofilm, using an optical microscope, is proposed based on the linear relation between the intensity of a pixel in biofilm images grabbed on the x-y plane and the corresponding number of cells in the z direction, which allows the calculation of the biofilm thickness. The method is intended to overcome the need for expensive microscopes to study biofilms. 相似文献
957.
Genomic checkpoints for exon 10 usage in the luteinizing hormone receptor type 1 and type 2 总被引:1,自引:0,他引:1
Gromoll J Lahrmann L Godmann M Müller T Michel C Stamm S Simoni M 《Molecular endocrinology (Baltimore, Md.)》2007,21(8):1984-1996
Alternative splicing is a hallmark of glycoprotein hormone receptor gene regulation, but its molecular mechanism is unknown. The LH receptor (LHR) gene possesses 11 exons, but exon 10 is constitutively skipped in the New World monkey lineage (LHR type 2), whereas it is constitutively spliced in the human (LHR type 1). This study identifies the regulatory elements of exon 10 usage. Sequencing of genomic marmoset DNA revealed that the cryptic LHR exon 10 is highly homologous to exon 10 from other species and displays intact splice sites. Functional studies using a minigene approach excluded the contribution of intronic, marmoset-specific long interspersed nucleotide-1 elements to exon 10 skipping. Sequencing of the genomic regions surrounding exon 10 from several primate lineages, sequence comparisons including the human and mouse LHR gene, revealed the presence of unique nucleotides at 3'-intronic position -19 and -10 and at position +26 within exon 10 of the marmoset LHR. Exon trap experiments and in vitro mutagenesis of these nucleotides resulted in the identification of a composite regulatory element of splicing consisting of cis-acting elements represented by two polypyrimidine tracts and a trans-acting element within exon 10, which affect the secondary RNA structure. Changes within this complex resulted either in constitutive exon inclusion, constitutive skipping, or alternative splicing of exon 10. This work delineates the molecular pathway leading to intronization of exon 10 in the LHR type 2 and reveals, for the first time, the essential function of regulatory and structural elements involved in glycoprotein hormone receptor splicing. 相似文献
958.
959.
Toni Mingozzi Giampiero Masciari Giuseppe Paolillo Brunella Pisani Manuela Russo Alessandro Massolo 《Biodiversity and Conservation》2007,16(12):3519-3541
Loggerhead turtle Caretta caretta nesting in Italy had been reported to be limited to the Pelagian Islands and only sporadically elsewhere. As presence of
loggerhead turtle nests had occasionally been reported (1988–1999) along about 200 km of the Ionian coast of Calabria, we
carried out a project to assess the actual state of the nesting population between 2000 and 2004. We divided the coastline
in two sectors (A: 52 km, and B: 146 km) that were monitored from mid-June to end of July for a total of n = 174 monitoring days and 1,813.6 km patrolled on foot with different intensities (extensive versus intensive). In sector
B, through extensive monitoring we did not find any emergence tracks, but in sector A by intensive survey (2002–2004: one
survey/3.64 days) we detected 3–8 nests/year. In total, 25 nests (both observed and reported), were recorded in our study
area, and an assessment of a total of 15–16 nests/year was suggested. These figures, within the national scenario depicted
from the review of known nesting events in the last 40 years (88 records concerning more than 143–144 nests), show that loggerhead
turtle nesting has been underestimated in Italy, due to inadequate monitoring protocols, and that nesting is more frequent
than expected (at least 30–40 nests/year). Conservation strategies in Italy should then focus not only on the reduction of
mortality at sea, but also include large-scale actions to preserve scattered (but regular) nesting events. 相似文献
960.
Temporal responses of transcripts, enzyme activities and metabolites after adding sucrose to carbon-deprived Arabidopsis seedlings 总被引:9,自引:0,他引:9