bluuebunny/crossref_metadata_2025_split huggingface dataset:
Impact of amino acid substitutions in the core region of HCV on multistep hepatocarcinogenesis
Authors: Fukuhara Takasuke , Takeishi Kazuki , Toshima Takeo , Morita Kazutoyo , Ueda Shigeru , Iguchi Tomohiro , Nagata Shigeyuki , Sugimachi Keishi , Ikegami Toru , Gion Tomonobu , Soejima Yuji , Taketomi Akinobu , Maehara Yoshihiko 
Published: September 2009

Aim: The core protein of hepatitis C virus (HCV) has multiple functions for not only viral replication but also hepatocellular carcinogenesis. A significant association of the substitutions in the core region with hepatocarcinogenesis has recently been reported. In this report, we evaluated the association of the substitutions in the core region with multistep hepatocarcinogenesis.Methods: Sixty‐nine non‐cancerous and cancerous liver tissues were obtained from the patients with primary developed hepatocellular carcinoma (HCC) due to HCV and 17 cirrhotic liver tissues were obtained from the patients without HCC. A sequence analysis of the core protein of HCV was performed and the association between the substitution rates in the core gene and the degree of fibrosis or steatosis during the primary development of HCC and tumor differentiation was analyzed.Results: The substitution rates of amino acid 70, 75, 91 and 147 exceeded 25% (amino acid 70, 51%; 75, 45%; 91, 36%; 147, 30%). All substitution rates were comparable among cancerous and non‐cancerous region of patients with HCC and non‐cancerous region without HCC. The substitution rates of these four amino acids were not associated with the degree of fibrosis, steatosis or tumor differentiation during the primary development of HCC. In addition, the substitution rates were comparable between the patients with or without HCC. The cumulative substitution numbers in the core region were also not associated with the degree of fibrosis and steatosis.Conclusions: It is possible that the substitutions in the core region are not associated with HCV‐related multistep hepatocarcinogenesis.
Susceptibility to experimental biliary atresia linked to different hepatic gene expression profiles in two mouse strains
Authors: Leonhardt Johannes , Kuebler Joachim F. , Turowski Carmen , Tschernig Thomas , Geffers Robert , Petersen Claus 
Published: September 2009

Aim:  To compare hepatic gene expression during the development of experimental biliary atresia (BA) in two different mouse strains.Methods:  Balb/c mice and C57Black/6 (Black/6) mice were infected with rhesus rotavirus (RRV) postpartum, clinical signs of BA and survival were noted. Liver sections were assessed for cluster of differentiation antigen (CD) 3, CD4 and CD8 expression, and the hepatic virus load was determined. Second, mice of both strains were sacrificed three days after infection. Isolated hepatic RNA was subjected to gene expression analysis using Affymetrix Gene Chip MOE 430 2.0.Results:  The incidence of BA was significantly lower in Black/6 mice compared to Balb/c mice (13.5% vs. 67%, P < 0.05). The mean virus titers were higher in mice with BA compared to mice without BA. Different gene profiles three days after virus infection were noted, with differential expression of 201 genes, including those regulating apoptosis, nucleic acid binding, transport function and particularly the immune response (chemokine C‐C motif ligand 2, toll‐like receptor 3, CD antigen 14, chemokine (C‐X‐C motif) ligands 10 and 11). This correlated with a significant increase of CD4 positive cells only in Balb/c mice with BA compared to healthy mice (13.5 vs. 5.0; P < 0.05). Black/6 mice did not exhibit any significant increase of CD3 or CD4 leukocytes despite cholestasis.Conclusion:  The different susceptibility to experimental BA was associated with an increase of CD4 T‐cells in the liver of Balb/c mice, which is linked to different gene profiles at the onset of bile duct obstruction.
Antiangiogenesis gene armed tumor‐targeting adenovirus yields multiple antitumor activities in human HCC xenografts in nude mice
Authors: Fang Lin , Pu Ying‐yan , Hu Xiao‐cui , Sun Li‐jun , Luo Hong‐mei , Pan Shao‐kun , Gu Jian‐zhong , Cao Xiang‐rong , Su Chang‐qing 
Published: September 2009

Aim:  Gene therapy represents a promising therapeutic strategy for hepatocellular carcinoma (HCC). To improve the ratio of killing efficacy on tumor cells to side‐effect on normal cells, we constructed an oncolytic adenovirus vector, AdSu‐hE, expressing the human endostatin (hE) gene, in which the chimeric promoter of human epidermal growth factor receptor 2 enhancer and human telomerase reverse transcriptase promoter was used to control the adenoviral E1a gene.Methods:  Tumor‐selective replication of adenovirus AdSu‐hE and its concomitant expression of endostatin were measured by 50% tissue culture infective dose method, fluorescent protein expression, Western blot and enzyme linked immunosorbent assay in cancer and normal cell lines. The antitumor efficacy was observed in nude mice bearing human HCCs.Results:  The oncolytic adenovirus AdSu‐hE replicated restrictedly in telomerase‐positive cancer cells and resulted in oncolysis, but did not replicate in normal cell lines. Along with virus replication, AdSu‐hE mediated 5‐fold increased expression of endostatin in tumor cells compared with that in normal cells. Moreover, AdSu‐hE expressed more endostatin in cancer cells than the non‐replicative adenovirus vector Ad‐hE. In vivo administration of the oncolytic adenovirus AdSu‐hE into HCC‐bearing nude mice produced a significant tumor reduction by synergistic effects of virus oncolysis and endostatin antiangiogenesis.Conclusion:  The oncolytic virus with antiangiogenesis gene driven by the chimeric promoter has an improved killing efficacy on tumor cells, and may be useful for cancer gene therapy.
Complex analysis of cyclin D1 expression in mantle cell lymphoma: two cyclin D1-negative cases detected
Authors: Stefancikova L , Moulis M , Fabian P , Falkova I , Vasova I , Kren L , Macak J , Smardova J 
Published: September 2009

Background and Aim:The cytogenetic and diagnostic hallmark of mantle cell lymphoma (MCL) is translocation t(11;14)(q13;q32), resulting in overexpression of cyclin D1. Cyclin D1 expression was analysed in 32 cases of MCL.Methods:The t(11;14) translocation was detected by fluorescence in situ hybridisation, level of cyclin D1 mRNA by competitive RT-PCR, and level of cyclin D1 and D2 proteins by immunohistochemistry and/or immunoblotting.Results:In 30 cases, the presence of translocation t(11;14), a high level of cyclin D1 mRNA, and a high level of the cyclin D1 protein were confirmed. Two cyclin D1-negative cases overexpressing cyclin D2 were detected by immunoblotting.Conclusions:There are rare cyclin D1-negative cases of MCL overexpressing cyclin D2. Anti-cyclin D1 antibodies with low specificity can bind both cyclin D1 and cyclin D2, thus providing false cyclin D1-positive signals in immunohistochemical analysis.
Primary cutaneous Ewing sarcoma/primitive neuroectodermal tumour: a clinicopathological analysis of seven cases highlighting diagnostic pitfalls and the role of FISH testing in diagnosis
Authors: Shingde M V , Buckland M , Busam K J , McCarthy S W , Wilmott J , Thompson J F , Scolyer R A 
Published: September 2009

Aims:To perform a clinicopathological analysis of a series of primary cutaneous Ewing sarcomas/primitive neuroectodermal tumours (ES/PNET) to highlight the pathological features, discuss the differential diagnosis, emphasise the role of molecular testing (particularly fluorescence in situ hybridisation, FISH) in diagnosis and outline the patients’ clinical course.Methods:Seven cases of primary cutaneous ES/PNET were identified from the authors’ consultation files.Results:The patients were aged 16–61 years (median 25). Five were female and two were male. Five cases involved the limbs and two the trunk. Five were initially misdiagnosed (three as carcinoma and two as melanoma). All cases were characterised histologically by sheet-like growth of small round cells with little cytoplasm and showed strong membranous staining for CD99 and positive but variable staining for FLI-1. Six patients showed an EWS rearrangement (five on FISH analysis and one on RT-PCR). All tumours were completely excised. Three patients received adjuvant chemotherapy, one of whom also received radiotherapy. Follow-up was available in all cases (range 11–57 months; median 41). No recurrences or metastases occurred.Conclusions:Although rare, primary cutaneous ES/PNET should be considered in the differential diagnosis of cutaneous “small blue cell tumours”. Immunostaining for FLI-1 and molecular testing for evidence of an EWS rearrangement are useful ancillary investigations to confirm the diagnosis. The prognosis of primary cutaneous ES/PNET appears to be more favourable than extracutaneous ES/PNET.
Prevalence of haemoglobinopathies in 34 030 healthy adults in Tehran, Iran
Authors: Ashtiani M T H , Monajemzadeh M , Sina A H , Berenji F , Abdollahi M , Said M G , Alam M 
Published: September 2009

Background:Haemoglobinopathies are a group of inherited disorders of haemoglobin synthesis. Their frequency varies considerably with geographic location and ethnic group.Aims:To establish the prevalence of haemoglobinopathies in a mainly healthy Iranian population.Methods:All files of the haematology unit of the Boghrat laboratory over a period of 10 years (1998–2007) were analysed in relation to the age, sex, full blood count, haemoglobin electrophoresis results, high performance liquid chromatography (HPLC) findings, and iron profile of healthy subjects referred for consultation before marriage. Other tests were performed if indicated.Results:There were 34 030 files; 13 432 (39.5%) were for men, and 20 567 (60.4%) for women. 0.74% of subjects (255) showed a haemoglobinopathy. The distribution of variant haemoglobins in these 255 subjects was: Hb D 75.67% (193 cases), Hb S 4.7%, Hb E 3.13%, Hb O-Arab 1.96% and Hb Lepore 0.39%. A fast haemoglobin was found in 4.71% of subjects. Of the subjects tested, 13.2% (4478) had β-thalassaemia minor, 0.2% (52) β-thalassaemia intermedia and 0.1% (30) β-thalassaemia major.Conclusions:In comparison with other parts of world, there is a different pattern of haemoglobinopathy with a high prevalence of Hb D, which appears to be Hb D Iran.
MULTISCALED CROSS-CORRELATION DYNAMICS IN FINANCIAL TIME-SERIES
Authors: CONLON T. , RUSKIN H. J. , CRANE M. 
Published: September 2009

The cross-correlation matrix between equities comprises multiple interactions between traders with varying strategies and time horizons. In this paper, we use the Maximum Overlap Discrete Wavelet Transform to calculate correlation matrices over different time–scales and then explore the eigenvalue spectrum over sliding time-windows. The dynamics of the eigenvalue spectrum at different times and scales provides insight into the interactions between the numerous constituents involved. Eigenvalue dynamics are examined for both medium, and high-frequency equity returns, with the associated correlation structure shown to be dependent on both time and scale. Additionally, the Epps effect is established using this multivariate method and analyzed at longer scales than previously studied. A partition of the eigenvalue time-series demonstrates, at very short scales, the emergence of negative returns when the largest eigenvalue is greatest. Finally, a portfolio optimization shows the importance of time–scale information in the context of risk management.
Weathering of granite and granitic regolith in Corsica: short-term
10
Be versus long-term thermochronological constraints
Authors: Kuhlemann Joachim , Krumrei Ingrid , Danišík Martin , Borg Klaas van der 
Published: September 2009

Abstract

In situ
10
Be concentrations in granites on Corsica (Mediterranean), exposed to subalpine climate, yield weathering rates of between 9 and 20 mm ka
−1
, when averaged over the last 30–100 ka. Weathering rates rise with increasing precipitation and brittle deformation. Thermal history modelling of apatite fission-track (AFT) data confirms that average denudation rates of 5–20 mm ka
−1
were typical during the Neogene. Short- and long-term denudation rates are in the same range and indicate that a late Neogene global increase in denudation rates has probably not affected geomorphically stable uplifted palaeosurfaces of hilly to low mountainous local relief. A Southwards decrease in short- and long-term denudation rates indicate a linear relationship with decreasing precipitation. Post-glacial downwearing of moraine matrix, as constrained by soil-derived humic etching of dated glacial boulders, yields 40–140 mm ka
−1
, which indicates a poor preservation potential of moraines older than the last glaciation. This weathering rate is of the order of 3 times faster than that found for long-term regolith formation from granites based on of geomorphic evidence.
Post Pan-African thermo-tectonic evolution of the north Mozambican basement and its implication for the Gondwana rifting. Inferences from
40
Ar/
39
Ar hornblende, biotite and titanite fission-track dating
Authors: Daszinnies M. C. , Jacobs J. , Wartho J.-A. , Grantham G. H. 
Published: September 2009

Abstract

This research paper investigates the thermo-tectonic history of the north Mozambican basement subsequent to the Pan-African metamorphism. Six
40
Ar/
39
Ar hornblende, three
40
Ar/
39
Ar biotite and 25 titanite fission-track data place new constraints on the earliest timing of rifting in the central sector of Gondwana, and demonstrate a close linkage between the geometric rift configuration and the ductile metamorphic basement fabrics during the initial dispersal of the supercontinent.

The
40
Ar/
39
Ar hornblende and biotite ages range from
c
. 542 to 456 Ma and from
c
. 448 to 428 Ma, respectively. These data record slow basement cooling after the latest Pan-African metamorphism at rates of
c
. 7–11 °C Ma
−1
between Early and Late Ordovician times. Locally, syn- to post-tectonic granitoid emplacements around 500–450 Ma delayed basement cooling to Late Ordovician–Early Silurian times. The titanite fission-track (TFT) ages fall into two age groups of
c
. 378–327 Ma and
c
. 284–219 Ma. The older TFT ages record very slow cooling from the Late Ordovician–Early Silurian to below 275±25 °C in the Late Devonian–Early Carboniferous at slow rates of less than 1 °C Ma
−1
. This slow cooling is related to decreasing denudation in association with the establishment of pre-Karoo peneplains in central Gondwana. The younger TFT ages record denudation due to rift flank uplift in the context of initial Gondwana disintegration in the Mozambican sector. Corresponding Early–Late Permian crustal extension proceeded obliquely to a NW–SE tensional palaeo-stress field and was associated with a brittle reactivation of easterly trending ductile basement fabrics. In total, up to ≤9–12 km of denudation is deduced from the TFT results since Permo-Carboniferous times.
Combined titanite and apatite fission-track data from Gjelsvikfjella, East Antarctica – another piece of a concealed intracontinental Permo-Triassic Gondwana rift basin?
Authors: Emmel B. , Jacobs J. , Daszinnies M. C. 
Published: September 2009

Abstract
Titanite and apatite fission-track ages from Gjelsvikfjella and the eastern Mühlig–Hofmann Mountains, East Antarctica, range between 516±50 and 323±30 Ma and 366±16 and 186±9 Ma, respectively. The thermochronological data set indicates differential cooling of two tectonic blocks (Hochlinfjellet–Festninga and Risemedet). Inverse modelled time–temperature paths suggest that the Hochlinfjellet–Festninga block cooled at first below 60 °C during the mid-Palaeozoic, whereas the Risemedet block cooled during the earliest Triassic. Differential cooling is most probably related to physical separation along active faults, which is associated with Gondwana-wide intracontinental rifting. This tectonic activity shaped the landscape in the study area along structures running perpendicular to the continental margin of Dronning Maud Land. A rift locus was possibly located along the Penck–Jutul graben west of the study area. In contrast to other parts of Dronning Maud Land, Jurassic magmatism and initial break-up between East Africa and East Antarctica did not influence the apatite FT data. Modelled apatite fission-track data indicate the onset of final cooling since the Early Cretaceous, suggesting post-Cretaceous unroofing of the palaeosurfaces in eastern Dronning Maud Land.
Quantitative constraints on mid- to shallow-crustal processes using the zircon (U–Th)/He thermochronometer
Authors: Dobson Katherine J. , Persano Cristina , Stuart Finlay M. 
Published: September 2009

Abstract

Despite the potential of zircon He thermochronometry for constraining rock thermal histories, it remains less commonly exploited than the apatite He chronometer. In part, this is due to the more challenging analytical techniques required to extract He, U and Th. Here we present a new method for the routine determination of zircon (U–Th)/He ages, and demonstrate how it can be used to constrain thermal histories and to quantify cooling in different tectonic settings. We present zircon (U–Th)/He ages that place a firm upper limit on the extent of denudation-induced cooling (
c
. 3 km) on the SE Australian passive margin; a region where synrift apatite fission-track and apatite (U–Th)/He ages have previously prevented quantitative constraint. We have also used the zircon (U–Th)/He thermochronometer to quantify the cooling of early Tertiary mafic plutons from Skye, Scotland, where the rate and timing of cooling cannot be determined using other thermochronometers.
Identification of a bacteriocin and its cognate immunity factor expressed by Moraxella catarrhalis
Authors: Attia Ahmed S , Sedillo Jennifer L , Hoopman Todd C , Liu Wei , Liu Lixia , Brautigam Chad A , Hansen Eric J 
Published: September 2009

Abstract

Background
Bacteriocins are antimicrobial proteins and peptides ribosomally synthesized by some bacteria which can effect both intraspecies and interspecies killing.

Results

Moraxella catarrhalis strain E22 containing plasmid pLQ510 was shown to inhibit the growth of M. catarrhalis strain O35E. Two genes (mcbA and mcbB) in pLQ510 encoded proteins predicted to be involved in the secretion of a bacteriocin. Immediately downstream from these two genes, a very short ORF (mcbC) encoded a protein which had some homology to double-glycine bacteriocins produced by other bacteria. A second very short ORF (mcbI) immediately downstream from mcbC encoded a protein which had no significant similarity to other proteins in the databases. Cloning and expression of the mcbI gene in M. catarrhalis O35E indicated that this gene encoded the cognate immunity factor. Reverse transcriptase-PCR was used to show that the mcbA, mcbB, mcbC, and mcbI ORFs were transcriptionally linked. This four-gene cluster was subsequently shown to be present in the chromosome of several M. catarrhalis strains including O12E. Inactivation of the mcbA, mcbB, or mcbC ORFs in M. catarrhalis O12E eliminated the ability of this strain to inhibit the growth of M. catarrhalis O35E. In co-culture experiments involving a M. catarrhalis strain containing the mcbABCI locus and one which lacked this locus, the former strain became the predominant member of the culture after overnight growth in broth.

Conclusion
This is the first description of a bacteriocin and its cognate immunity factor produced by M. catarrhalis. The killing activity of the McbC protein raises the possibility that it might serve to lyse other M. catarrhalis strains that lack the mcbABCI locus, thereby making their DNA available for lateral gene transfer.
Applied public health research - falling through the cracks?
Authors: Simmons Rebecca K , Ogilvie David , Griffin Simon J , Sargeant Lincoln A 
Published: September 2009

Abstract

Background
There is a degree of dissonance between the types of evaluative research required by organisations providing or commissioning health care, those recommended by organisations developing evidence-based guidance, and those which research funding bodies are prepared to support.

Methods
We present a case study of efforts to establish a pragmatic but robust evaluation of local exercise referral schemes. We considered the epidemiological, ethical and practical advantages and disadvantages of a number of study designs and applied for research funding based on an uncontrolled design, outlining the difficulties of carrying out a randomised controlled trial to evaluate an existing service.

Results
Our proposal was praised for its relevance and clear patient outcomes, but the application was twice rejected because both funders and reviewers insisted on a randomised controlled trial design, which we had found to be impractical, unacceptable to service users and potentially unethical.

Conclusion
The case study highlights continuing challenges for applied public health research in the current funding climate.
Blockade of Wnt-1 signaling leads to anti-tumor effects in hepatocellular carcinoma cells
Authors: Wei Wei , Chua Mei-Sze , Grepper Susan , So Samuel K 
Published: September 2009

AbstractBackgroundHepatocellular carcinoma (HCC) is an aggressive cancer, and is the third leading cause of cancer death worldwide. Standard therapy is ineffective partly because HCC is intrinsically resistant to conventional chemotherapy. Its poor prognosis and limited treatment options make it critical to develop novel and selective chemotherapeutic agents. Since the Wnt/β-catenin pathway is essential in HCC carcinogenesis, we studied the inhibition of Wnt-1-mediated signaling as a potential molecular target in HCC.ResultsWe demonstrated that Wnt-1 is highly expressed in human hepatoma cell lines and a subgroup of human HCC tissues compared to paired adjacent non-tumor tissues. An anti-Wnt-1 antibody dose-dependently decreased viability and proliferation of Huh7 and Hep40 cells over-expressing Wnt-1 and harboring wild type β-catenin, but did not affect normal hepatocytes with undetectable Wnt-1 expression. Apoptosis was also observed in Huh7 and Hep40 cells after treatment with anti-Wnt-1 antibody. In these two cell lines, the anti-Wnt-1 antibody decreased β-catenin/Tcf4 transcriptional activities, which were associated with down-regulation of the endogenous β-catenin/Tcf4 target genes c-Myc, cyclin D1, and survivin. Intratumoral injection of anti-Wnt-1 antibody suppressedin vivotumor growth in a Huh7 xenograft model, which was also associated with apoptosis and reduced c-Myc, cyclin D1, and survivin expressions.ConclusionOur results suggest that Wnt-1 is a survival factor for HCC cells, and that the blockade of Wnt-1-mediated signaling may offer a potential pathway-specific therapeutic strategy for the treatment of a subgroup of HCC that over-expresses Wnt-1.