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81.
Synthesis of most of the plasma proteins is one of the main functions of the hepatocytes. Albumin synthesis is quantitatively
the most abundant. In the present study we investigated albumin- and alpha-fetoprotein-gene-expression, and the function of
the secretory apparatus during rat liver development. To this purpose we used the method of radioactive biosynthetic labeling
of newly synthesized albumin and alpha-fetoprotein (AFP) to monitor the secretory capacity of endodermal cells derived from
ventral foregut region (embryonic day 10, E10), and of embryonic and fetal hepatoblasts. Synthesis and secretion of albumin
and AFP were already detected in the low numbered ventral foregut endodermal cells; fibrinogen synthesis was detectable in
the E12 hepatoblasts, which were in higher number. The whole secretory machinery was functional from the earliest stages of
liver development, and the speed of secretion was comparable with that of the adult hepatocytes. There was almost 4-fold increase
of hepatoblasts cell volume in fetal stage compared with embryonic stage. The model used suggests that the hepatocyte secretory
apparatus is already functional before the emergence of the liver bud. This is the first comparative report to analyze the
hepatocyte secretory function, cell proliferation and cell volume during liver development. 相似文献
82.
Devescovi G Bigirimana J Degrassi G Cabrio L LiPuma JJ Kim J Hwang I Venturi V 《Applied and environmental microbiology》2007,73(15):4950-4958
Burkholderia glumae is an emerging rice pathogen in several areas around the world. Closely related Burkholderia species are important opportunistic human pathogens for specific groups of patients, such as patients with cystic fibrosis and patients with chronic granulomatous disease. Here we report that the first clinical isolate of B. glumae, strain AU6208, has retained its capability to be very pathogenic to rice. As previously reported for rice isolate B. glumae BGR1 (and also for the clinical isolate AU6208), TofI or TofR acyl homoserine lactone (AHL) quorum sensing played a pivotal role in rice virulence. We report that AHL quorum sensing in B. glumae AU6208 regulates secreted LipA lipase and toxoflavin, the phytotoxin produced by B. glumae. B. glumae AU6208 lipA mutants were no longer pathogenic to rice, indicating that the lipase is an important virulence factor. It was also established that type strain B. glumae ATCC 33617 did not produce toxoflavin and lipase and was nonpathogenic to rice. It was determined that in strain ATCC 33617 the LuxR family quorum-sensing sensor/regulator TofR was inactive. Introducing the tofR gene of B. glumae AU6208 in strain ATCC 33617 restored its ability to produce toxoflavin and the LipA lipase. This study extends the role of AHL quorum sensing in rice pathogenicity through the regulation of a lipase which was demonstrated to be a virulence factor. It is the first report of a clinical B. glumae isolate retaining strong rice pathogenicity and finally determined that B. glumae can undergo phenotypic conversion through a spontaneous mutation in the tofR regulator. 相似文献
83.
The capability of Agaricus bisporus tyrosinase to catalyze the oxidation of tyrosine residues of silk sericin was studied under homogeneous reaction conditions, by using sericin peptides purified from industrial wastewater as the substrate. Tyrosinase was able to oxidize about 57% of sericin-bound tyrosine residues. The reaction rate was higher than with silk fibroin, but lower than with other silk-derived model peptides, i.e. tryptic and chymotryptic soluble peptide fractions of silk fibroin, suggesting that the size and the molecular conformation of the substrate influenced the kinetics of the reaction. The concentration of tyrosine in oxidized sericin samples decreased gradually with increasing the enzyme-to-substrate ratio. The average molecular weight of sericin peptides significantly increased by oxidation, indicating that cross-linking occurred via self-condensation of o-quinones and/or coupling with the free amine groups of lysine and, probably, with sulfhydryl groups of cysteine. The high temperature shift of the main thermal transitions observed in the differential scanning calorimetry curves confirmed the formation of peptide species with higher molecular weight and higher thermal stability. Fourier transform-infrared spectra of oxidized sericin samples showed slight changes related to the loss of tyrosine and formation of oxidation products. Oxidized sericin peptides were able to undergo non-enzymatic coupling with chitosan. Infrared spectra provided clear evidence of the formation of sericin-chitosan bioconjugates under homogeneous reaction conditions. Spectral changes in the NH stretching region seem to support the formation of bioconjugates via the Michael addition mechanism. 相似文献
84.
Altered anxiety-related behavior in nociceptin/orphanin FQ receptor gene knockout mice 总被引:3,自引:1,他引:2
Studies showed that nociceptin/orphanin FQ (N/OFQ) peptide receptor (NOP) agonists produce anxiolytic-like actions, while little is known about the effects of blockade of NOP receptor signaling in anxiety. To this aim, we investigated the behavioral phenotype of NOP receptor gene knockout mice (NOP(-/-)) in different assays. In the elevated plus-maze and light-dark box, NOP(-/-) mice displayed increased anxiety-related behavior. In the novelty-suppressed feeding behavior and elevated T-maze, NOP(-/-) mice showed anxiolytic-like phenotype, while no differences were found in the open-field, hole-board, marble-burying, and stress-induced hyperthermia. Altogether, these findings suggest that the N/OFQ-NOP receptor system modulates anxiety-related behavior in a complex manner. 相似文献
85.
Siligardi G Ruzza P Hussain R Cesaro L Brunati AM Pinna LA Donella-Deana A 《Amino acids》2012,42(4):1361-1370
HS1 is a protein involved in erythroid proliferation and apoptotic cell death, containing several structurally significant
motifs including a C-terminal SH3 domain. HPK1 is a member of the Ste20-related kinase family, which contains four proline-rich
sequences and is constitutively associated with HS1 in hematopoietic cells. Recombinant fusion protein GST-SH3HS1 was expressed to assess the binding properties of 16 peptides derived from the HPK1 proline-rich regions. The binding affinities
were determined by non-immobilized ligand interaction assay by circular dichroism. Our results revealed that the classical
PxxPxK class II binding motif is not sufficient to induce the interaction with the GST-SH3HS1 domain, an event dependent on the presence of additional basic residue(s) located at the C-terminus of the PxxPxK motif:
Lys−5 in P2 peptide and Lys−8 in P4c peptide. Lys replacement by Arg residues decreases the ligand binding affinity. The finding that both SH3HS1 domain and full-length HS1 protein bind to P2 peptide with similar affinity demonstrates that the whole protein sequence does not affect the interaction properties of
the domain. In silico models of SH3HS1 as a complex with P2 or P4c highlight the domain residues that interact with the recognition determinants of the peptide ligand and that cooperate in
the complex stabilization. 相似文献
86.
87.
Pere P. Simarro Giuliano Cecchi José R. Franco Massimo Paone Abdoulaye Diarra José Antonio Ruiz-Postigo Eric M. Fèvre Raffaele C. Mattioli Jean G. Jannin 《PLoS neglected tropical diseases》2012,6(10)
Background
Human African trypanosomiasis (HAT), also known as sleeping sickness, persists as a public health problem in several sub-Saharan countries. Evidence-based, spatially explicit estimates of population at risk are needed to inform planning and implementation of field interventions, monitor disease trends, raise awareness and support advocacy. Comprehensive, geo-referenced epidemiological records from HAT-affected countries were combined with human population layers to map five categories of risk, ranging from “very high” to “very low,” and to estimate the corresponding at-risk population.Results
Approximately 70 million people distributed over a surface of 1.55 million km2 are estimated to be at different levels of risk of contracting HAT. Trypanosoma brucei gambiense accounts for 82.2% of the population at risk, the remaining 17.8% being at risk of infection from T. b. rhodesiense. Twenty-one million people live in areas classified as moderate to very high risk, where more than 1 HAT case per 10,000 inhabitants per annum is reported.Discussion
Updated estimates of the population at risk of sleeping sickness were made, based on quantitative information on the reported cases and the geographic distribution of human population. Due to substantial methodological differences, it is not possible to make direct comparisons with previous figures for at-risk population. By contrast, it will be possible to explore trends in the future. The presented maps of different HAT risk levels will help to develop site-specific strategies for control and surveillance, and to monitor progress achieved by ongoing efforts aimed at the elimination of sleeping sickness. 相似文献88.
Sabrina Grecchi Giuliano Mazzini Antonella Lisa Marie-Therese Armentero Roberto Bergamaschi Alfredo Romani Fabio Blandini Carol Di Perri Anna Ivana Scovassi 《PloS one》2012,7(9)
Multiple Sclerosis (MS) is a chronic disease of the central nervous system, the etiology of which, although not completely known, involves inflammation and autoimmunity. In the present study we aimed at identifying molecular markers of apoptosis, cellular stress and DNA damage in isolated peripheral blood mononuclear cells (PBMCs) of MS patients. The analysis was carried on 19 relapsing-remitting untreated MS patients and 13 healthy individuals. We investigated the emergency-driven synthesis of poly(ADP-ribose) (PAR), the expression level of the constitutive enzyme poly(ADP-ribose) polymerase-1 (PARP-1) and the DNA damage-induced phosphorylation of histone H2AX. PAR accumulation, PARP-1 and phosphorylated H2AX (γH2AX) were detected by immunofluorescence experiments on PBMCs isolated from 19 patients and 13 healthy volunteers. Our results show for the first time a net increased amount in PAR and γH2AX in MS patients compared to healthy individuals. Patients were further subdivided in three groups, according to the neuroimaging (MRI)-based classification of disease phase. Remarkably, we found a positive correlation between the level of γH2AX and MS aggressiveness. In addition, apoptosis in PBMCs was monitored by flow cytometry of both phosphatidylserine exposure (revealed by Annexin V-FITC labeling) and membrane permeability to propidium iodide. Our observations provide the evidence that the number of apoptotic cells was significantly higher in patients compared to healthy individuals, thus suggesting that apoptosis could affect MS lymphocyte function. 相似文献
89.
90.
The pharmaceutical industry is currently facing the challenge of maintaining increased efficiency and productivity while contending with a deluge of genomic and high-throughput screening data. To ease the bottlenecks at target validation and lead optimization, the industry must look to the living cell, the ultimate target of all drugs, as a source of new biological knowledge. This new 'cell-centric' perspective must integrate reagents that report on the state of molecular processes within the cell, automated detection and analysis of these processes, and cellular knowledge, building into a single platform. 相似文献