bluuebunny/crossref_metadata_2025_split huggingface dataset:
The Pro variant of the p53 codon 72 polymorphism is associated with hepatocellular carcinoma in Moroccan population
Authors: Ezzikouri Sayeh , El feydi Abdellah Essaid , Chafik Abdelaziz , Benazzouz Mustapha , El kihal Latifa , Afifi Rajae , Hassar Mohammed , Pineau Pascal , Benjelloun Soumaya 
Published: June 2007

Aim:  Codon 72 polymorphism of the p53 gene has been implicated in cancer risk, and it has been suggested that it may have an impact on the clinical outcome of the disease. Our objective was to evaluate the association between p53 polymorphism at codon 72 and hepatocellular carcinoma (HCC) in the Moroccan population.Methods:  Genomic DNA was extracted from peripheral blood cells of 96 patients with HCC and 222 controls without HCC matched for age, gender and ethnicity. Codon 72 polymorphism of p53 was identified by PCR‐restriction fragment length polymorphism, confirmed by sequencing.Results:  Patients with HCC had higher frequencies of Pro/Pro (13.5% vs. 6.3%, P < 0.02) than controls and consequently a 2.3‐fold increased risk of liver cancer development (odds ratio [OR], 2.304; 95% confidence interval [CI], 1.014–5.234). In addition, we found a significant association between the p53Arg72Pro polymorphism and the female gender in HCC. Men with Pro/Pro genotype had a 1.57‐fold increased risk for HCC, whereas the corresponding genotype in women had a 4.4‐fold increased risk of HCC (OR, 4.4; 95% CI, 1.18–16.42). No correlation between the polymorphism and HCC risk was found when comparing the hepatitis C virus (HCV)‐positive cases to HCV‐positive controls. However, HCV‐negative subjects and Pro/Pro genotype had a 3.31‐fold increased risk for HCC.Conclusion:  These results provide evidence that p53 polymorphism at codon 72 is a modifier of hepatocarcinogenesis, especially in women and HCV‐negative subjects.
Keratin inclusions alter cytosolic protein localization in hepatocytes
Authors: Hanada Shinichiro , Harada Masaru , Kawaguchi Takumi , Kumemura Hiroto , Taniguchi Eitaro , Koga Hironori , Yanagimoto Chikatoshi , Maeyama Michiko , Ueno Takato , Sata Michio 
Published: June 2007

Aim:  Mallory bodies have been observed in various liver diseases, however, the precise mechanism and significance of these structures have yet to be determined.Methods:  Previously we reported on the redistribution of cytosolic proteins to keratin inclusions in mutant keratin 18‐transfected cells. In this study, we treated green fluorescent protein‐tagged wild‐type keratin 18‐transfected cells with several proteasome inhibitors and performed immunofluorescent analyses.Results:  Proteasome inhibitors induced intracellular keratin inclusions, and desmoplakin, zonula occludens‐1 and β‐catenin were relocated to keratin inclusions, while theintegral membrane proteins were intact. The cytosolic proteins, 14‐3‐3 ζ protein and glucose‐6‐phosphate dehydrogenase were also relocated to inclusions. Moreover, E‐cadherin, a basolateral membrane protein, was present on both the apical and basolateral domains in inclusion‐containing cells.Conclusion:  These data are identical to those in the mutant keratin 18 transfection study and suggest that keratin inclusions induced by different treatments affect localization of various cytosolic components, which may influence cellular functions performed by these proteins.
Potentiation of isoniazid‐induced liver toxicity by rifampicin in a combinational therapy of antitubercular drugs (rifampicin, isoniazid and pyrazinamide) in Wistar rats: A toxicity profile study
Authors: Tasduq Sheikh Abdullah , Kaiser Peerzada , Sharma Subhash Chander , Johri Rakesh Kamal 
Published: June 2007

Aim: Biochemical characterization of long‐term toxic manifestations of anti‐tubercular (anti‐TB) drugs – rifampicin (RIF), isoniazid (INH) and pyrazinamide (PZA) – individually and in two combinations: (i) RIF + INH, and (ii) RIF + INH + PZA in Wistar rats.Methods: Animals received anti‐TB drugs – alone or in combination – once daily p.o. for up to 90 days (doses, in mg/kg: RIF, 250; INH, 50; PZA, 100). Assays for alanine aminotransferase (ALT), alkaline phosphatase (ALP), bilirubin (serum) and lipid peroxidation (LPO), glutathione (GSH), glutathione peroxidase (GPx), catalase, Na+K+‐ATPase and CYP 2E1 (liver) were performed to assess liver toxicity. Clinical biochemistry was done by commercial kits. Determinations were made at 0, 15, 30 and 90 days of treatment schedule.Results: Anti‐TB drugs‐treated animals showed abnormal rises or falls (>1.5–2 fold) in the serum/liver parameters. Mild hyperlipidemia, hypercholesterolemia and hyperuricemia were the other pathologies. Of all the treated groups, INHalone or in combination with other drugs produced a progressive enhancement of toxicity over 15–90 days. Thein vivoresults were further supported byin vitroresults (MTT assay, GSH and LPO) in primary cultures of rat hepatocyte. Results indicated that anti‐TB drugs in combination: (i) caused membrane damage resulting in leakage of ALT, ALP and bilirubin; (ii) caused imbalance in endogenous enzymatic oxidant–antioxidant defense via increased lipid peroxidation and in glutathione homeostasis; and (iii) enhanced the CYP 2E1‐mediated bioactivation mechanism.Conclusion: Toxicity manifestations seemed to be heptocytic injury targeted at hepatocytes, bile ducts or sinusoidal cells related to hepatitis and primary biliary cholestasis.
Protective effect of non‐mitogenic human acidic fibroblast growth factor on hepatocyte injury
Authors: Xu Hua , Hai Guang‐fan , Xiang Ji‐zhou , Yao Cheng‐can , Zheng Qing , Zhang Qi‐hao , Hong Hai 
Published: June 2007

Aim:  To study whether non‐mitogenic human acidic fibroblast growth factor (nm‐haFGF) has protective effects on H2O2‐induced hepatocyte injury in vitro and CCl4‐induced hepatocyte injury in vivo.Methods:  (i) HL‐7702 hepatocytes were incubated with different concentrations of nm‐haFGF for 12 h, and then the activity of lactate dehydrogenase (LDH) in culture medium was detected, and genomic DNA electrophoresis analysis was observed after being exposed to H2O2 (8 mmol/L) for 4 h. Proximately, apoptotic rates and protein expressions of Bcl‐2 and Bax of HL‐7702 cell were detected after being exposed to H2O2 (0.2 mmol/L) for 20 h. (ii) Being injected intraperitoneally with nm‐haFGF, mice were treated with CCl4 intraperitoneally to induce hepatic injury. Twenty‐four hours later, serum aspartate aminotransferase (AST) and alanine aminotransferase (ALT) were measured and histopathologic changes were evaluated.Results:  (i) In vitro tests: LDH activities and apoptotic rates decreased, the protein expression of Bcl‐2 increased and Baxdecreased in nm‐haFGF‐treated groups at the concentrations of 100 150 and 200 ng/mL, compared with that in the model control group, which was treated with H2O2 alone. The genomic DNA remained nearly intact at the concentrations of 150 and 200 ng/mL. (ii) In vivo tests: serum ALT and AST in nm‐haFGF‐treated groups (10 μg/kg and 20 μg/kg) were much lower as compared to the model control group, which was treated with CCl4 alone. Histological examination showed that nm‐haFGF markedly ameliorated hepatocytes vacuolation, cloudy swelling and inflammatory cells infiltration induced by CCl4.Conclusion:  nm‐haFGF had protective effects against H2O2‐induced hepatocyte injury in vitro and CCl4‐induced acute liver injury in vivo.
Local interaction of apoptotic hepatocytes and Kupffer cells in a rat model of systemic endotoxemia
Authors: Eipel Christian , Hirschmann Martin , Abshagen Kerstin , Menger Michael D. , Vollmar Brigitte 
Published: June 2007

Aim:  There is strong evidence that hepatocellular apoptosis is not only initiated by circulating blood cells which become adherent within the endotoxemic liver, but also contributes to further sustain the inflammatory cell–cell response.Methods:  Because previous studies assumed the importance of the role of cellular cross‐talk in mediating inflammatory liver injury, we herein examined the activation of Kupffer cells (KCs) and their spatial coincidence with intrahepatic leukocyte adherence and hepatocellular apoptosis at 6 h after intraperitoneal exposure of rats with lipopolysaccharide (10 mg/kg).Results:  In vivo multifluorescence microscopy revealed liver injury including nutritive perfusion failure, tissue hypoxia, leukocyte accumulation, as well as KC activation and parenchymal apoptotic cell death. Detailed spatial analysis revealed frequent colocalization of activated KCs with apoptotic hepatocytes. Colocalization was absent in saline‐treated controls.Colocalization was confirmed by histochemistry, which showed ED1‐positive KCs neighboring and engulfing TUNEL‐positive hepatocytes. Colocalization of KCs with leukocytes ranged between 4% and 5% and did not increase in endotoxemic animals. Taken together, the present results indicate that apoptotic cell death of hepatocytes may stimulate phagocytosis by neighboring KCs. Direct KC–leukocyte contact seems not to be mandatory for cellular communication in the process of hepatocellular apoptosis.Conclusion:  With respect to the fundamental importance of cell apoptosis, improved knowledge of these cell–cell interactions might allow the development of new therapeutic strategies through the regulation of apoptotic cell death.
A
Bacillus anthracis
-Based In Vitro System Supports Replication of Plasmid pXO2 as Well as Rolling-Circle-Replicating Plasmids
Authors: Tinsley Eowyn , Khan Saleem A. 
Published: June 2007

ABSTRACT

Capsule-encoding virulence plasmid pXO2 of
Bacillus anthracis
is predicted to replicate by a unidirectional theta-type mechanism. To gain a better understanding of the mechanism of replication of pXO2 and other plasmids in
B. anthracis
and related organisms, we have developed a cell-free system based on
B. anthracis
that can faithfully replicate plasmid DNA in vitro. The newly developed system was shown to support the in vitro replication of plasmid pT181, which replicates by the rolling-circle mechanism. We also demonstrate that this system supports the replication of plasmid pXO2 of
B. anthracis
. Replication of pXO2 required directional transcription through the plasmid origin of replication, and increased transcription through the origin resulted in an increase in plasmid replication.
Effectiveness of Standard UV Depuration at Inactivating
Cryptosporidium parvum
Recovered from Spiked Pacific Oysters (
Crassostrea gigas
)
Authors: Sunnotel O. , Snelling W. J. , McDonough N. , Browne L. , Moore J. E. , Dooley J. S. G. , Lowery C. J. 
Published: June 2007

ABSTRACT

When filter-feeding shellfish are consumed raw, because of their ability to concentrate and store waterborne pathogens, they are being increasingly associated with human gastroenteritis and have become recognized as important pathogen vectors. In the shellfish industry, UV depuration procedures are mandatory to reduce pathogen levels prior to human consumption. However, these guidelines are based around more susceptible fecal coliforms and
Salmonella
spp. and do not consider
Cryptosporidium
spp., which have significant resistance to environmental stresses. Thus, there is an urgent need to evaluate the efficiency of standard UV depuration against the survival of
Cryptosporidium
recovered from shellfish. Our study found that in industrial-scale shellfish depuration treatment tanks, standard UV treatment resulted in a 13-fold inactivation of recovered, viable
C. parvum
oocysts from spiked (1 × 10
6
oocysts liter
−1
) Pacific oysters. Depuration at half power also significantly reduced (
P
< 0.05; ninefold) the number of viable oocysts recovered from oysters. While UV treatment resulted in significant reductions of recovered viable oocysts, low numbers of viable oocysts were still recovered from oysters after depuration, making their consumption when raw a public health risk. Our study highlights the need for increased periodic monitoring programs for shellfish harvesting sites, improved depuration procedures, and revised microbial quality control parameters, including
Cryptosporidium
assessment, to minimize the risk of cryptosporidiosis.
Evaluation of Culture Methods To Identify Bovine Feces with High Concentrations of
Escherichia coli
O157
Authors: Fox J. Trent , Renter David G. , Sanderson Michael W. , Thomson Daniel U. , Lechtenberg Kelly F. , Nagaraja T. G. 
Published: June 2007

ABSTRACT

Our objective was to evaluate methods for identifying cattle with high concentrations of
Escherichia coli
O157 in their feces. In two experiments, feces were collected from cattle orally inoculated with nalidixic acid (Nal)-resistant
E. coli
O157, and direct plating of diluted feces on sorbitol MacConkey agar with cefixime and potassium tellurite (CT-SMAC) containing Nal was considered the gold standard (GS) method. In experiment 1, methods evaluated were preenrichment direct streak, immunomagnetic separation with most probable number (MPN), and postenrichment direct streak with MPN, all using CT-SMAC. The mean concentration of Nal-resistant
E. coli
O157 in samples (
n
= 59) by use of the GS was 3.6 log
10
CFU/g. The preenrichment streak detected >3.0 log
10
CFU/g samples with a 74.4% sensitivity and 68.8% specificity. Postenrichment direct streak-MPN and immunomagnetic separation-MPN concentrations were correlated significantly with GS concentrations (
r
= 0.53 and
r
= 0.39, respectively). In experiment 2 (480 samples), pre- and postenrichment direct streaking performed in triplicate and spiral plating on CT-SMAC were evaluated. For preenrichment streaks, sensitivity was 79.7% and specificity was 96.7% for detecting >3.0 log
10
CFU/g when the criterion was positive cultures on at least two plates. For spiral plating at that concentration, sensitivity and specificity were 83.9% and 56.3%, respectively. Postenrichment streaking performed relatively poorly. Triplicate preenrichment streaks of 1:10-diluted feces on CT-SMAC may be useful for identifying cattle shedding high concentrations of
E. coli
O157. Estimates of sensitivity and specificity enable appropriate application of methods and interpretation of results and may enhance applied research, surveillance, and risk assessments.
Lack of Electricity Production by
Pelobacter carbinolicus
Indicates that the Capacity for Fe(III) Oxide Reduction Does Not Necessarily Confer Electron Transfer Ability to Fuel Cell Anodes
Authors: Richter Hanno , Lanthier Martin , Nevin Kelly P. , Lovley Derek R. 
Published: June 2007

ABSTRACT

The ability of
Pelobacter carbinolicus
to oxidize electron donors with electron transfer to the anodes of microbial fuel cells was evaluated because microorganisms closely related to
Pelobacter
species are generally abundant on the anodes of microbial fuel cells harvesting electricity from aquatic sediments.
P. carbinolicus
could not produce current in a microbial fuel cell with electron donors which support Fe(III) oxide reduction by this organism. Current was produced using a coculture of
P. carbinolicus
and
Geobacter sulfurreducens
with ethanol as the fuel. Ethanol consumption was associated with the transitory accumulation of acetate and hydrogen.
G. sulfurreducens
alone could not metabolize ethanol, suggesting that
P. carbinolicus
grew in the fuel cell by converting ethanol to hydrogen and acetate, which
G. sulfurreducens
oxidized with electron transfer to the anode. Up to 83% of the electrons available in ethanol were recovered as electricity and in the metabolic intermediate acetate. Hydrogen consumption by
G. sulfurreducens
was important for ethanol metabolism by
P. carbinolicus
. Confocal microscopy and analysis of 16S rRNA genes revealed that half of the cells growing on the anode surface were
P. carbinolicus
, but there was a nearly equal number of planktonic cells of
P. carbinolicus
. In contrast,
G. sulfurreducens
was primarily attached to the anode.
P. carbinolicus
represents the first Fe(III) oxide-reducing microorganism found to be unable to produce current in a microbial fuel cell, providing the first suggestion that the mechanisms for extracellular electron transfer to Fe(III) oxides and fuel cell anodes may be different.
Transposon Insertion Reveals pRM, a Plasmid ofRickettsia monacensis
Authors: Baldridge Gerald D. , Burkhardt Nicole Y. , Felsheim Roderick F. , Kurtti Timothy J. , Munderloh Ulrike G. 
Published: June 2007

ABSTRACTUntil the recent discovery of pRF inRickettsia felis, the obligate intracellular bacteria of the genusRickettsia(Rickettsiales:Rickettsiaceae) were thought not to possess plasmids. We describe pRM, a plasmid fromRickettsia monacensis, which was detected by pulsed-field gel electrophoresis and Southern blot analyses of DNA from two independentR. monacensispopulations transformed by transposon-mediated insertion of coupled green fluorescent protein and chloramphenicol acetyltransferase marker genes into pRM. Two-dimensional electrophoresis showed that pRM was present in rickettsial cells as circular and linear isomers. The 23,486-nucleotide (31.8% G/C) pRM plasmid was cloned from the transformant populations by chloramphenicol marker rescue of restriction enzyme-digested transformant DNA fragments and PCR using primers derived from sequences of overlapping restriction fragments. The plasmid was sequenced. Based on BLAST searches of the GenBank database, pRM contained 23 predicted genes or pseudogenes and was remarkably similar to the larger pRF plasmid. Two of the 23 genes were unique to pRM and pRF among sequenced rickettsial genomes, and 4 of the genes shared by pRM and pRF were otherwise found only on chromosomes ofR. felisor the ancestral group rickettsiaeR. belliiandR. canadensis. We obtained pulsed-field gel electrophoresis and Southern blot evidence for a plasmid inR. amblyommiiisolate WB-8-2 that contained genes conserved between pRM and pRF. The pRM plasmid may provide a basis for the development of a rickettsial transformation vector.
Activation of the
ADE
Genes Requires the Chromatin Remodeling Complexes SAGA and SWI/SNF
Authors: Koehler Rebecca N. , Rachfall Nicole , Rolfes Ronda J. 
Published: June 2007

ABSTRACT

The activation of the
ADE
regulon genes requires the pair of transcription factors Bas1 and Pho2. In a genome-wide screen for additional regulators of the pathway, strains with mutations in multiple subunits of the chromatin remodeling complexes SAGA and SWI/SNF were uncovered. These mutants exhibited decreased expression of an
ADE5,7-lacZ
reporter and native
ADE
compared to the wild-type strains, but the expression of the
BAS1
and
PHO2
genes was not substantially decreased. An unregulated Bas1-Pho2 fusion protein depended upon SAGA and SWI/SNF activity to promote transcription of a reporter. A significant but low-level association of Gcn5-myc and Snf2-myc with the
ADE5,7
promoter was independent of adenine growth conditions and independent of the presence of the activator proteins Bas1 and Pho2. However, the increase in occupancy of Bas1 and Pho2 at
ADE5,7
depended on both SAGA and SWI/SNF. The loss of catalytic activity of both SAGA and SWI/SNF complexes in the
gcn5
Δ
snf2
Δ double mutant was severely detrimental to
ADE-lacZ
reporter expression and native
ADE
gene expression, indicating complementary roles for these complexes. We conclude that Bas1 and Pho2 do not recruit the SAGA and SWI/SNF complexes to the
ADE5,7
promoter but that the remodeling complexes are necessary to increase the binding of Bas1 and Pho2 in response to the adenine regulatory signal. Our data support the model that the SAGA and SWI/SNF complexes engage in global surveillance that is necessary for the specific response by Bas1 and Pho2.
Alteration of the Protein Kinase Binding Domain Enhances Function of the
Saccharomyces cerevisiae
Molecular Chaperone Cdc37
Authors: Ren Min , Santhanam Arti , Lee Paul , Caplan Avrom , Garrett Stephen 
Published: June 2007

ABSTRACT

Cdc37 is a molecular chaperone that has a general function in the biogenesis of protein kinases. We identified mutations within the putative “protein kinase binding domain” of Cdc37 that alleviate the conditional growth defect of a strain containing a temperature-sensitive allele,
tpk2
(Ts), of the cyclic AMP-dependent protein kinase (PKA). These dominant mutations alleviate the temperature-sensitive growth defect by elevating PKA activity, as judged by their effects on PKA-regulated processes, localization and phosphorylation of the PKA effector Msn2, as well as in vitro PKA activity. Although the
tpk2
(Ts) growth defect is also alleviated by Cdc37 overproduction, the
CDC37
dominant mutants contain wild-type Cdc37 protein levels. In addition,
Saccharomyces cerevisiae
Ste11 protein kinase has an elevated physical interaction with the altered Cdc37 protein. These results implicate specific amino-terminal residues in the interaction between Cdc37 and client protein kinases and provide further genetic and biochemical support for a model in which Cdc37 functions as a molecular chaperone for protein kinases.
Flagellar Elongation and Gene Expression inChlamydomonas reinhardtii
Authors: Periz Goran , Dharia Darshita , Miller Steven H. , Keller Laura R. 
Published: June 2007

ABSTRACTLithium (Li+) affects the physiology of cells from a broad range of organisms including plants and both vertebrate and invertebrate animals. Although its effects result presumably from changes in gene expression elicited by its interaction with intracellular signal transduction pathways, the molecular mechanisms of Li+action are not well understood. The biflagellate green algaChlamydomonas reinhardtiiis an ideal genetic model for the integration of the effects on Li+on signal transduction, gene expression, and aspects of flagellar biogenesis. Li+causesC. reinhardtiiflagella to elongate to ∼1.4 times their normal length and blocks flagellar motility (S. Nakamura, H. Tabino, and M. K. Kojima, Cell Struct. Funct. 12:369-374, 1987). We report here that Li+treatment increases the abundance of several flagellar mRNAs, including α- and β-tubulin and pcf3-21. Li+-induced flagellar gene expression occurs in cells pretreated with cycloheximide, suggesting that the abundance change is a response that does not require new protein synthesis. Deletion analysis of the flagellar α1-tubulin gene promoter showed that sequences necessary for Li+-induced expression differed from those for acid shock induction and contain a consensus binding site for CREB/ATF and AP-1 transcription factors. These studies suggest potential promoter elements, candidate factors, and signal transduction pathways that may coordinate theC. reinhardtiicellular response to Li+.
Integration of Rotation and Piston Motions in Coiled-Coil Signal Transduction
Authors: Gao Rong , Lynn David G. 
Published: June 2007

ABSTRACTA coordinated response to a complex and dynamic environment requires an organism to simultaneously monitor and interpret multiple signaling cues. In bacteria and some eukaryotes, environmental responses depend on the histidine autokinases (HKs). For example, VirA, a large integral membrane HK fromAgrobacterium tumefaciens, regulates the expression of virulence genes in response to signals from multiple molecular classes (phenol, pH, and sugar). The ability of this pathogen to perceive inputs from different known host signals within a single protein receptor provides an opportunity to understand the mechanisms of signal integration. Here we exploited the conserved domain organization of the HKs and engineered chimeric kinases to explore the signaling mechanisms of phenol sensing and pH/sugar integration. Our data implicate a piston-assisted rotation of coiled coils for integration of multiple inputs and regulation of critical responses during pathogenesis.