bluuebunny/crossref_metadata_2025 huggingface dataset:
Modulation of anti‐adhesion molecule MUC‐1 is associated with arctiin‐induced growth inhibition in PC‐3 cells
Authors: Huang Dong‐Ming , Guh Jih‐Hwa , Chueh Shih‐Chieh , Teng Che‐Ming
Published: March 2004

BACKGROUND

Lignans have been reported to possess anti‐tumor activity in various cancer cells. However, their anticancer effects in human prostate cancer have not been well established. Here, we examine the effect of arctiin, a lignan compound, on growth regulation in prostate cancer PC‐3 cells. We postulated that arctiin modulates the attachment/detachment of PC‐3 cells and we investigated the role of arctiin on MUC‐1 expression.

METHODS

The effect of arctiin on PC‐3 cell growth was examined using an MTT assay method and cell number was calculated by means of a standard regression line. The expressions of MUC‐1 and integrins α2, α5, and β1 were detected using FACScan flow cytometric analysis. Levels of MUC‐1 mRNA were determined using reverse transcriptase PCR (RT‐PCR).

RESULTS

Treatment of PC‐3 cells with arctiin decreased the cell number in a concentration‐ and time‐dependent manner in serum‐containing condition. Arctiin preferentially induced cell detachment, but did not have anti‐proliferation or cytotoxic effects in PC‐3 cells. The arctiin‐induced effect was inhibited by cycloheximide, indicating that protein synthesis was required. FACScan flow cytometric analysis demonstrated that arctiin increased the expression of the anti‐adhesion mucin MUC‐1, but did not affect integrin expression in PC‐3 cells. The arctiin‐induced increase in MUC‐1 protein expression was due to up‐regulation of mRNA, as revealed by RT‐PCR analysis.

CONCLUSIONS

Arctiin significantly induces cell detachment and decreases the cell numbers via the up‐regulation of MUC‐1 mRNA and protein in PC‐3 cells. © 2004 Wileey‐Liss, Inc.
Androgen receptor CAG repeat length correlates with semen PSA levels in adolescence
Authors: Giwercman Yvonne Lundberg , Richthoff Jonas , Lilja Hans , Anderberg Camilla , Abrahamsson Per‐Anders , Giwercman Aleksander
Published: March 2004

BACKGROUND

Androgens exert their action through the androgen receptor (AR). The length of the AR CAG repeat is inversely correlated to receptor function and short CAG length might be a risk factor for development of prostate cancer. Our aim was to investigate whether CAG repeat number might have an impact on prostate function in adolescence.

METHODS

AR genotyping was performed by direct sequencing of leukocyte DNA from 274 military conscripts. All men underwent endocrine evaluation and semen analysis.

RESULTS

PSA in seminal plasma, total sperm count and motility all are inversely correlated with CAG numbers (rho = −0.128, P = 0.038; rho = −0.156, P = 0.010; rho = −0.158, P = 0.011), whereas serum levels of free testosterone (rho = 0.132; P = 0.029) and luteinizing hormone (rho = 0.126; P = 0.037) are positively correlated to CAG length. No correlation between seminal PSA and serum testosterone, neither free nor total, was found.

CONCLUSIONS

In adolescence, AR genotype, but not serum testosterone, is associated with the level of seminal PSA. © 2004 Wileey‐Liss, Inc.
Murine prostate cancer inhibits both in vivo and in vitro generation of dendritic cells from bone marrow precursors
Authors: Tourkova Irina L. , Yamabe Kazuo , Foster Barbara , Chatta Gurkamal , Perez Lori , Shurin Galina V. , Shurin Michael R.
Published: March 2004

BACKGROUND

There is increasing evidence to suggest that dendritic cells (DC) are functionally impaired in tumor bearing hosts. However there is little or no data on the effects of murine prostate cancer (CaP) on DC generation from bone marrow precursors.

METHODS

Flow cytometry, mixed leukocyte reactions (MLR), and immunohistochemical analyses were used to characterize DC in CaP.

RESULTS

DC generated in the presence of CaP cell lines RM1 and the cell line C2 from the transgenic adenocarcinoma of the mouse prostate (TRAMP) mouse in a Transwell system expressed significantly lower levels of DC differentiation markers. This effect was confirmed when TK‐neo‐transfected RM1 cells were directly added to DC cultures and eliminated 5 days later using gancyclovir (GCV). Furthermore, co‐incubation of DC with CaP cells resulted in a decrease in the stimulatory capacity of DC to induce T cell proliferation in the MLR assay. These results were further confirmed in vivo in two different murine models of CaP: i) DC generated from mice intrafemorally injected with TK‐neo‐transfected RM1 cells; and ii) in DC generated from TRAMP mice.

CONCLUSIONS

The generation and function of DC are significantly suppressed in the CaP microenvironment in both in vivo and in vitro murine models. © 2004 Wileey‐Liss, Inc.
Canine prostate stimulates osteoblast function using the endothelin receptors
Authors: LeRoy Bruce E. , Sellers Rani S. , Rosol Thomas J.
Published: March 2004

BACKGROUND

Bone metastases are common in humans and dogs with late‐stage prostate cancer. A unique feature of prostate cancer metastases is new bone formation at metastatic sites (“osteoblastic metastases”). Many carcinomas that metastasize to bone cause bone destruction, not new bone formation. The mechanisms by which prostate cancer induces bone formation at sites of bone metastasis are not well understood. We hypothesized that stimulation of osteoblasts by prostate tissue at metastatic sites was due to the paracrine actions of growth factors produced by prostate epithelial cells.

METHODS

We have previously shown that normal canine prostate tissue induced new bone formation when implanted adjacent to the calvarium of nude mice. To complement this in vivo model, we developed an in vitro system of prostate‐stimulated osteoblast function to investigate mechanisms of prostate‐induced new bone formation.

RESULTS

We found that treatment of cultured rat calvaria for 24 hr with proteins from normal dog prostate stimulated alkaline phosphatase activity in a dose‐dependent manner 4–6 fold compared to controls. Stimulation began approximately 8 hr after treatment, and was diminished after 72 hr. Calvaria treated with homogenates of normal dog salivary gland, kidney, bladder, and muscle did not increase ALP activity. Pretreatment of the calvaria for 1 hr with endothelin antagonists, but not anti‐parathyroid hormone‐related protein (PTHrP) antibody or indomethacin, abrogated the stimulation of ALP.

CONCLUSIONS

Our results indicated that osteoblast activation by canine prostate occurs via an endothelin‐dependent mechanism, and that PTHrP or prostaglandin synthase‐mediated pathways are likely not involved. This is a reliable, reproducible assay for determining the roles of molecules important in the activation of osteoblasts by the prostate. © 2004 Wileey‐Liss, Inc.
Overexpressing leptin genetic polymorphism (−2548 G/A) is associated with susceptibility to prostate cancer and risk of advanced disease
Authors: Ribeiro Ricardo , Vasconcelos André , Costa Sandra , Pinto Daniela , Morais Antonio , Oliveira Jorge , Lobo Francisco , Lopes Carlos , Medeiros Rui
Published: March 2004

BACKGROUND

Leptin has been consistently associated with angiogenesis and tumoral growth. A G/A single nucleotide polymorphism (SNP) at the −2548 site in leptin gene (LEP) is associated with overexpression of leptin (A‐allele).

METHODS

We evaluated DNA samples from 268 (536 alleles) unrelated individuals, 118 healthy controls (HCs) and 150 prostate cancer (PC) patients, for leptin gene (LEP) locus −2548 genotypes.

RESULTS

We found an overrepresentation of the A‐allele in PC patients and that there is a significantly higher risk for PC among A carriers (OR = 1.60; confidence interval (CI), 1.13–2.28, P = 0.008). Linear trend analysis showed that quantitative increase of A‐allele presence was associated with significantly higher risk for PC (P = 0.003) in heterozygous (OR = 2.11; CI, 1.20–3.71) and homozygous (OR = 2.93; CI, 1.27–6.75) genotypes. Furthermore, the AA and AG genotypes represent significantly higher risk (OR = 4.67; CI, 1.69–12.88 and OR = 2.58; CI, 1.19–5.58, respectively) for advanced disease.

CONCLUSIONS

According to our results we hypothesize that the polymorphism in LEP gene may be relevant to PC risk and progression, supporting the hypothesis for leptin involvement in cancer ethiopathogenesis. © 2004 Wiley‐Liss, Inc.
USF2 is connected to GAAAATATGATA element and associates with androgen receptor‐dependent transcriptional regulation in prostate
Authors: Kivinen Anne , Patrikainen Lila , Kurkela Riitta , Porvari Katja , Vihko Pirkko
Published: March 2004

BACKGROUND

We have previously identified a GAAAATATGATA binding site (pros) of a transcription factor involved in prostatic and androgen‐dependent gene regulation. We now purified the potential factors interacting with the pros and characterized their co‐operation with the androgen receptor (AR).

METHODS

Sequence‐specific DNA affinity chromatography, mass‐spectrometry, electromobility shift assays, supershifts, glutathione‐S‐transferase pull‐downs, and transient transfections.

RESULTS

Several proteins bound to the pros site, but only upstream stimulatory factor 2 (USF2) was confirmed to be part of the transcription factor complex. Weak interaction was detected between AR and the transcription factor complex. Physical proximity between the androgen response element (ARE) and the pros was shown to be important for their co‐operation. In the presence of pros and androgen, AR achieves its maximal efficiency even at low concentrations.

CONCLUSIONS

The protein complex binding to the GAAAATATGATA site does not have a significant independent function, but may interact with AR if GAAAATATGATA is physically close to the ARE and enhances the transactivation function of AR. © 2004 Wiley‐Liss, Inc.
Serum osteoprotegerin (OPG) levels are associated with disease progression and response to androgen ablation in patients with prostate cancer
Authors: Eaton Colby L. , Wells Jason M. , Holen Ingunn , Croucher Peter I. , Hamdy Freddie C.
Published: March 2004

BACKGROUND

Osteoprotegerin (OPG) is a tumour and/or bone derived factor that may protect tumour cells from apoptosis. In this study, we have measured serum OPG levels in untreated prostate cancer patients with advanced prostate cancer compared to patients with organ confined disease and in treated patients receiving androgen ablation.

METHODS

Serum OPG levels were measured by ELISA in samples collected from 104 patients with either newly diagnosed (n = 59) or advanced prostate cancer treated by androgen ablation (n = 45) and compared with levels in serum from patients with benign prostatic hyperplasia (BPH) (n = 10) and young healthy men (n = 10).

RESULTS

Untreated patients with locally advanced disease had significantly higher OPG levels than those with organ confined disease. Patients with advanced disease responding to androgen ablation (serum PSA < 1 ng/ml) had serum OPG levels that were significantly lower than those with clinically progressing disease (PSA > 10 ng/ml). OPG levels in the latter were not significantly different from levels in patients with early signs of biochemical progression (PSA >1 but <10 ng/ml).

CONCLUSIONS

OPG is a potential new marker, which is elevated in the serum of patients with advanced prostate cancer and may be an indicator of early disease progression. © 2004 Wiley‐Liss, Inc.
Screening decreases prostate cancer mortality: 11‐year follow‐up of the 1988 Quebec prospective randomized controlled trial
Authors: Labrie Fernand , Candas Bernard , Cusan Lionel , Gomez Jose Luis , Bélanger Alain , Brousseau G. , Chevrette Eric , Lévesque Jacques
Published: March 2004

PURPOSE

This clinical trial is aimed at evaluating the impact of prostate cancer screening on cancer‐specific mortality.

SUBJECTS AND METHODS

Forty‐six thousand four hundred and eighty‐six (46,486) men aged 45–80 years registered in the electoral roll of the Quebec city area were randomized in 1988 between screening and no screening. Screening included measurement of serum prostatic specific antigen (PSA) using 3.0 ng/ml as upper limit of normal and digital rectal examination (DRE) at first visit. At follow‐up visits, serum PSA only was used.

RESULTS

Seventy‐four (74) deaths from prostate cancer occurred in the 14,231 unscreened controls while 10 deaths were observed in the screened group of 7,348 men during the first 11 years following randomization. Median follow‐up of screened men was 7.93 years. A Cox proportional hazards model of the age at death from prostate cancer shows a 62% reduction (P < 0.002, Fisher's exact test) of cause‐specific mortality in the screened men (P = 0.005). These results are in agreement with the continuous decrease of prostate cancer mortality observed in North America. © 2004 Wiley‐Liss, Inc.
Partitioning tracer tests as a remediation metric: Case study at naval amphibious base little creek, Virginia Beach, Virginia
Authors: Divine Craig E. , McCray John E. , Wolf Martin Leah M. , Blanford William J. , Blitzer David J. , Brusseau Mark L. , Boving Thomas B.
Published: March 2004

The partitioning tracer test (PTT) is a characterization tool that can be used to quantify the
porespace saturation (SN) and spatial distribution of dense nonaqueous phase liquids
(DNAPLs) in the subsurface. Because the method essentially eliminates data interpolation errors by
directly measuring a relatively large subsurface volume, it offers significant promise as a remediation metric
for DNAPL‐zone remediation efforts. This article presents, in detail, the design and results of field
PTTs conducted before and after a DNAPL‐zone treatment at the Naval Amphibious Base Little Creek,
Virginia Beach, Virginia. The results from different tracers yield a relatively large range in SN
estimates, indicating notable uncertainty and presenting significant challenges for meaningful interpretation.
Several potential interpretation methods are presented, resulting in an estimated DNAPL removal range of 15 to
109 L. While this range is large, it is consistent with the DNAPL removal (∼30 L) determined from
analysis of effluent concentration measurements collected during the remediation efforts. At this site, the
initial and final SN values are low, and the relatively inconsistent performance of the various
tracers indicates that these levels are near the lower practical quantification limit for these PTTs;
however, the effective lower quantification limit for these tests is unknown. Generally, an understanding of
lower quantification limits is particularly important for interpretation of post‐remediation PTTs because
SN values are likely to be low (due to remediation efforts) and the SN estimated
from the PTT may be used to predict long‐term dissolved plume behavior and assess associated
environmental risk. Partitioning tracer test quantification limits are test‐specific, as they are
dependent on a variety of factors including analytical uncertainty, tracer breakthrough characteristics, and
tracer data integration techniques. The results of this case study indicate that methods for estimating lower
quantification limits for field PTTs require further development. © 2004 Wiley Periodicals, Inc.
Identification of potential cell‐surface proteins in Candida albicans and investigation of the role of a putative cell‐surface glycosidase in adhesion and virulence
Authors: Alberti‐Segui Christine , Morales Arturo J. , Xing Heming , Kessler Marco M. , Willins Debra Aker , Weinstock Keith G. , Cottarel Guillaume , Fechtel Kim , Rogers Bruce
Published: March 2004

Cell‐surface proteins are attractive targets for the development of novel antifungals as they are more accessible to drugs than are intracellular targets. By using a computational biology approach, we identified 180 potential cell‐surface proteins in Candida albicans, including the known cell‐surface adhesin Als1 and other cell‐surface antigens, such as Pra1 and Csa1. Six proteins (named Csf1‐6 for cell‐surface factors) were selected for further biological characterization. First, we verified that the selected CSF genes are expressed in the yeast and/or hyphal form and then we investigated the effect of the loss of each CSF gene on cell‐wall integrity, filamentation, adhesion to mammalian cells and virulence. As a result, we identified Csf4, a putative glycosidase with an apparent orthologue in Saccharomyces cerevisiae (Utr2), as an important factor for cell‐wall integrity and maintenance. Interestingly, deletion of CSF4 also resulted in a defect in filamentation, a reduction in adherence to mammalian cells in an in vitro adhesion assay, and a prolongation of survival in an immunocompetent mouse model of disseminated candidiasis. A delay in colonization of key organs (e.g. kidney) was also observed, which is consistent with a reduction in virulence of the csf4‐deletion strain. These data indicate a key role for extracellular glycosidases in fungal pathogenesis and represent a new site for therapeutic intervention to cure and prevent fungal disease. Copyright © 2004 John Wiley & Sons, Ltd.
Expression of a plant serine O‐acetyltransferase in Saccharomyces cerevisiae confers osmotic tolerance and creates an alternative pathway for cysteine biosynthesis
Authors: Mulet Jose M. , Alemany Beatriz , Ros Roc , Calvete Juan J. , Serrano Ramon
Published: March 2004

Screening of a sugar beet (Beta vulgaris cv. Dita) cDNA library for clones able to confer osmotic tolerance to the osmosensitive gpd1 mutant of Saccharomyces cerevisiae identified a novel serine O‐acetyltransferase (BvSAT; EC 2.3.1.30). This enzyme is involved in cysteine biosynthesis in plants and bacteria, producing O‐acetylserine, which is converted into cysteine in a reaction catalysed by O‐acetylserine sulphydrylase (EC 4.2.99.8). This pathway is not conserved in yeast, where cysteine is synthesized in a four‐step pathway starting with homoserine and having O‐acetylhomoserine, homocysteine and cystathionine as intermediates. Expression of BvSAT in yeast takes advantage of the activity of yeast O‐acetylhomoserine sulphydrylase (MET15/MET17/MET25; EC 4.2.99.10) with O‐acetylserine as substrate and induces an alternative cysteine biosynthesis pathway. Our results imply that the resulting increase in cysteine production confers enhanced resistance against osmotic stress in the osmosensitive yeast strain. These data demonstrate that cysteine biosynthesis is a limiting factor in osmotic stress tolerance in yeast. Copyright © 2004 John Wiley & Sons, Ltd.
Isolation of an acetyl‐CoA synthetase gene (ZbACS2) from Zygosaccharomyces bailii
Authors: Rodrigues Fernando , Zeeman Anne‐Marie , Cardoso Helena , Sousa Maria João , Steensma H. Yde , Côrte‐Real Manuela , Leão Cecília
Published: March 2004

A gene homologous to Saccharomyces cerevisiae ACS genes, coding for acetyl‐CoA synthetase, has been cloned from the yeast Zygosaccharomyces bailii ISA 1307, by using reverse genetic approaches. A probe obtained by PCR amplification from Z. bailii DNA, using primers derived from two conserved regions of yeast ACS proteins, RIGAIHSVVF (ScAcs1p; 210–219) and RVDDVVNVSG (ScAcs1p; 574–583), was used for screening a Z. bailii genomic library. Nine clones with partially overlapping inserts were isolated. The sequenced DNA fragment contains a complete ORF of 2027 bp (ZbACS2) and the deduced polypeptide shares significant homologies with the products of ACS2 genes from S. cerevisiae and Kluyveromyces lactis (81% and 82% identity and 84% and 89% similarity, respectively). Phylogenetic analysis shows that the sequence of Zbacs2 is more closely related to the sequences from Acs2 than to those from Acs1 proteins. Moreover, this analysis revealed that the gene duplication producing Acs1 and Acs2 proteins has occurred in the common ancestor of S. cerevisiae, K. lactis, Candida albicans, C. glabrata and Debaryomyces hansenii lineages. Additionally, the cloned gene allowed growth of S. cerevisiae Scacs2 null mutant, in medium containing glucose as the only carbon and energy source, indicating that it encodes a functional acetyl‐CoA synthetase. Also, S. cerevisiae cells expressing ZbACS2 have a shorter lag time, in medium containing glucose (2%, w/v) plus acetic acid (0.1–0.35%, v/v). No differences in cell response to acetic acid stress were detected both by specific growth and death rates. The mode of regulation of ZbACS2 appears to be different from ScACS2 and KlACS2, being subject to repression by a glucose pulse in acetic acid‐grown cells. The nucleotide sequence of a common 5269 bp fragment has been deposited in the EMBL Data Library under Accession No. AJ314837. Copyright © 2004 John Wiley & Sons, Ltd.
GFP as a quantitative reporter of gene regulation in Candida albicans
Authors: Barelle Caroline J. , Manson Claire L. , MacCallum Donna M. , Odds Frank C. , Gow Neil A. R. , Brown Alistair J. P.
Published: March 2004

A system has been developed for the quantitative analysis of gene expression within individual Candida albicans cells in infected tissue. The system is based on the plasmid pGFP, which contains the codon‐optimized yeast enhanced green fluorescent protein (yEGFP; Cormack et al., 1997) cloned between a basal CaADH1 promoter and the ScCYC1 terminator on an integrating vector. Promoters were inserted into pGFP and GFP levels measured in individual cells by quantitative fluorescence microscopy. Analysis of pPCK1–GFP and pMET3–GFP fusions revealed that GFP folds rapidly following gene induction, and is turned over rapidly following gene repression. Hence, single cell fluorescence measurements are likely to reflect ongoing gene expression levels with reasonable accuracy. pACT1–GFP expression levels were relatively constant during growth of C. albicans in both yeast and hyphal forms, and during growth in vivo in the mouse model of systemic infection. Therefore, pACT1–GFP provides a useful control for this quantitative GFP‐based system in future analyses of C. albicans molecular responses during fungal infections. Copyright © 2004 John Wiley & Sons, Ltd.
The Saccharomyces cerevisiae alcohol acetyl transferase Atf1p is localized in lipid particles
Authors: Verstrepen Kevin J. , Van Laere Stijn D. M. , Vercammen Jo , Derdelinckx Guy , Dufour Jean‐Pierre , Pretorius Isak S. , Winderickx Joris , Thevelein Johan M. , Delvaux Freddy R.
Published: March 2004

The yeast alcohol acetyl transferase I, Atf1p, is responsible for the major part of volatile acetate ester production in fermenting Saccharomyces cerevisiae cells. Some of these esters, such as ethyl acetate and isoamyl acetate, are important for the fruity flavours of wine, beer and other fermented beverages. In order to reveal the subcellular localization of Atf1p and further unravel the possible physiological role of this protein, ATF1::GFP fusion constructs were overexpressed in brewer's yeast. The transformant strain showed a significant increase in acetate ester formation, similar to that of an ATF1 overexpression strain, indicating that the Atf1p–GFP fusion protein was active. UV fluorescence microscopy revealed that the fusion protein was localized in small, sphere‐like organelles. These organelles could be selectively stained by the fluorescent dye Nile red, indicating that they contained high amounts of neutral lipids and/or sterols, a specific characteristic of yeast lipid particles. Purification of lipid particles from wild type and ATF1 deletion cells confirmed that the Atf1p–GFP fusion protein was located in these organelles. Furthermore, a clear alcohol acetyl transferase activity could be measured in the purified lipid particles of both wild type and transformed cells. The localization of Atf1p in lipid particles may indicate that Atf1p has a specific role in the lipid and/or sterol metabolism that takes place in these particles. Copyright © 2004 John Wiley & Sons, Ltd.
Alcohol dehydrogenases that catalyse methyl formate synthesis participate in formaldehyde detoxification in the methylotrophic yeast Candida boidinii
Authors: Yurimoto Hiroya , Lee Bumjun , Yasuda Fumi , Sakai Yasuyoshi , Kato Nobuo
Published: March 2004

Methyl formate synthesis during growth on methanol by methylotrophic yeasts has been considered to play a role in formaldehyde detoxification. An enzyme that catalyses methyl formate synthesis was purified from methylotrophic yeasts, and was suggested to belong to a family of alcohol dehydrogenases (ADHs). In this study we report the gene cloning and gene disruption analysis of three ADH‐encoding genes in the methylotrophic yeast Candida boidinii (CbADH1, CbADH2 and CbADH3) in order to clarify the physiological role of methyl formate synthesis. From the primary structures of these three genes, CbAdh1 was shown to be cytosolic and CbAdh2 and CbAdh3 were mitochondrial enzymes. Gene products of CbADH1, CbADH2 and CbADH3 expressed in Escherichia coli showed both ADH‐ and methyl formate‐synthesizing activities. The results of gene‐disruption analyses suggested that methyl formate synthesis was mainly catalysed by a cytosolic ADH (CbAdh1), and this enzyme contributed to formaldehyde detoxification through glutathione‐independent formaldehyde oxidation during growth on methanol by methylotrophic yeasts. The GenBank/EMBL/DDBJ Accession Nos for CbADH1, CbADH2 and CbADH3 are AB125900, AB125901 and AB125902, respectively. Copyright © 2004 John Wiley & Sons, Ltd.
Mechanical environment alters tissue formation patterns during fracture repair
Authors: Smith‐Adaline E. A. , Volkman S. K. , Ignelzi M. A. , Slade J. , Platte S. , Goldstein S. A.
Published: March 2004

Fracture repair has previously been shown to be sensitive to mechanical environment, yet the specific relationship between strain character, magnitude and frequency, as well as other mechanical parameters, and tissue formation is not well understood. This study aimed to correlate strain distribution within the healing fracture gap with patterns of tissue formation using a rat model of a healing osteotomy subject to mechanical stimulation in bending. Finite element models based on realistic tissue distributions were used to estimate both the magnitude and spatial distribution of strains within the fracture gap. The spatial distribution of regenerating tissue was determined by microcomputed tomography and histology, and was confirmed using reverse transcription‐polymerase chain reaction (RT‐PCR). Results suggest that tensile strains suppress chondrogenesis during the mechanical stimulation period. After stimulation ends, however, tensile strains increased chondrogenesis followed by rapid bone formation. In contrast, in compressive environments, bone is formed primarily via intramembranous ossification. Taken together, these results suggest that intermittent tensile strains during fracture repair stimulate endochondral ossification and promote eventual bone healing compared to intermittent compressive strains and unstimulated fractures. Further understanding of these relationships may allow proposal of optimal therapeutic strategies for improvement of the fracture repair process. © 2004 Orthopaedic Research Society. Published y Elsevier Ltd. All rights reserved.
IMPROVING THE YIELD OF MUNGBEAN (VIGNA RADIATA) IN THE NORTH WEST FRONTIER PROVINCE OF PAKISTAN USING ON-FARM SEED PRIMING
Authors: RASHID A. , HARRIS D. , HOLLINGTON P. A. , RAFIQ M.
Published: March 2004

The effect of ‘on-farm’ seed priming – soaking seeds in water before surface-drying and sowing them – was tested for mungbean (Vigna radiata) in 15 irrigated on-station trials and four sets of rainfed, paired-plot, farmer-participatory trials over four contrasting years from 1999 to 2002 in the North West Frontier Province of Pakistan. The optimum soaking time was found to be between six and eight hours; eight hours was used in all the trials. Of the 19 trials, priming was significantly better than non-priming in 14 with a mean yield increase of 56%. In the remaining five trials there was no difference between treatments but in no case was priming worse than not priming. In a subset of 11 on-station trials in which management was considered to be optimal, yield declined in a linear fashion as the date of sowing was delayed. The rate of decline of about 30 kg ha−1 d−1 after 1st June was similar for both non-primed and primed crops, although the latter declined from a higher base. Farmers' yields were proportional to rainfall over the four years and the mean increase in grain yield due to priming in the 39 trials was 30%. Benefits from priming were the result of a combination of faster germination and emergence and more vigorous growth and development, leading to better crop stands and bigger, more productive plants. It was concluded that ‘on-farm’ seed priming is a low-cost, low-risk technology that has the potential to raise mungbean yields substantially thus making it a more attractive crop for farmers.
PRODUCTION METHODS AND FARMING SYSTEMS IN MAJOR BARLEY (HORDEUM VULGARE) GROWING REGIONS OF THE WEST BANK, PALESTINE
Authors: ABU-ALRUB IHSAN , JOMA ALA , CHRISTIANSE JØRGEN. L.
Published: March 2004

A survey of barley and barley-based farming systems was carried out in Palestine during the 2000 growing season to assess traditional cultivation methods and to analyse developments in the production systems. Seventy-six farmers in the three barley growing agro-ecological zones in the West Bank were included in the study. The research area encompasses a range of agro-ecological conditions, from high to low potential environments, strongly related to precipitation. Estimated grain yields varied from below 1000 kg ha−1 in the driest part of the Eastern Slopes zone to above 4000 kg ha−1 in the more fertile areas in the Central Highlands and Semi-Coastal zones. Barley was found to be closely linked to the dominant crop-livestock farming systems. Thus 84% of the farmers interviewed grew barley as a feed for their own livestock during the dry season. In the more fertile agro-ecological zones, the traditional farming system is shifting towards more intensive production methods with increased mechanization, mainly for land preparation, sowing, harvesting and use of fertilizer. Here animal production is becoming more intensive and a larger proportion of the farm products, including barley, is now produced for the market. Despite the relatively high yields, in comparison to other barley growing areas in the region, local barley landraces, particularly 6-rowed types, persist well and were preferred by 86% of the farmers interviewed. However attempts to modernize agriculture may result in the replacement of traditional barley landraces, and even the barley-livestock cropping system in the more fertile agro-ecological zones. An effort should therefore be made to conserve this valuable genetic resource.
THE INFLUENCE OF MINERAL FERTILIZER APPLICATION AND PLANT NUTRITION ON PLANT-PARASITIC NEMATODES IN UPLAND AND LOWLAND RICE IN CÔTE D'IVOIRE AND ITS IMPLICATIONS IN LONG TERM AGRICULTURAL RESEARCH TRIALS
Authors: COYNE D. L. , SAHRAWAT K. L. , PLOWRIGHT R. A.
Published: March 2004

Mineral fertilizer application and consequent plant nutrition has long been observed to influence associated plant-parasitic nematode population densities, offering the potential as a nematode management option. Observations were made on the influence of mineral fertilizer application on nematode populations on three separate long-term rice experiments, (differential mineral application on upland and on lowland rice, and P application on upland rice) undertaken between 1994 and 1997 in Côte d'Ivoire. In 1995, on upland rice, treatments with K or N withheld from the comprehensive mineral application treatment (range of elements including N, P, K, Ca, Mg and Zn) led to lower densities of Pratylenchus zeae at harvest than the comprehensive mineral application. By withholding K or Mg, Helicotylenchus pseudorobustus densities were greater than with either the control (no mineral application) or comprehensive mineral application in the same year. No differences were observed between treatments in 1994, or between treatments for densities of other nematode species present (Meloidogyne incognita, Criconemella tescorum) or for total nematode density. In the lowland rice trial, no treatment effects on nematode species (Hirschmanniella oryzae and Uliginotylenchus palustris) were observed. In the P application trial on a P-deficient Ultisol, Heterodera sacchari densities were lower in treatments receiving 180 kg P ha−1, than untreated in 1995; in 1996 no differences were observed between untreated and 135 kg P ha−1, while in 1997 higher densities of H. sacchari were present in 135 kg P ha−1 than untreated. Regression analysis of nematode densities against the mineral straw content in the P application trial revealed a negative correlation between M. incognita and Mn and Ca, and between P. zeae and Zn or Fe. A positive correlation was observed between Helicotylenchus spp. and Mg. This study provides strong arguments for taking plant parasitic nematodes into account when planning and executing long-term research trials.
TOWARDS A REGIONAL APPROACH TO RESEARCH FOR THE CGIAR AND ITS PARTNERS
Authors: DE JANVRY A. , KASSAM A. H.
Published: March 2004

At its International Centres Week in October 2000 (ICW2000), the Consultative Group on International Agricultural Research (CGIAR) adopted a new Vision and Strategy. This paper is about Plank 4 of the CGIAR's Vision and Strategy which calls for the adoption, in collaboration with national and regional partners, of a regional approach to research planning, priority setting and implementation. Given the poverty and impact focus of international public goods research, both national agricultural research systems (NARS) and the CGIAR have advantages in pursuing a regional approach as a component of their respective activities. For the NARS in the region, this means seeking advantages at the regional level that they could not derive solely from a national-level approach. For the CGIAR, this means seeking complementary gains that it could not achieve exclusively through a global or ecoregional approach. These mutual advantages open the door for partnerships in regional research between NARS and their regional organizations, and the CGIAR. The paper highlights the advantages as well as risks and limitations of a regional approach to research. Since ICW2000, all regional and sub-regional organizations and CGIAR Centres have taken action to facilitate consultation processes that could eventually lead to the establishment of a regional approach to research for the CGIAR and NARS. The paper notes some emerging lessons, and takes a forward look.
Atmospheric water vapor complexes and the continuum
Authors: Daniel John S. , Solomon Susan , Kjaergaard Henrik G. , Schofield Daniel P.
Published: March 2004

Estimates of absorption optical depths for the bound complexes H2O‐H2O and the sum of H2O‐N2, H2O‐O2, and H2O‐Ar at visible and near‐infrared wavelengths are compared to the same quantities calculated from a frequently used water continuum parameterization (MT_CKD) and from a theoretical far wing water vapor lineshape theory. The temperature dependences of some of these optical depths are also compared. The comparisons suggest qualitatively that water complexes may contribute to the continuum at these wavelengths, and show that the temperature dependence of the continuum might provide insight into the role of the complexes in the atmosphere. Because of the dearth of laboratory measurements of the continuum at these wavelengths, and because the current estimates for the equilibrium constants of these water vapor complexes remain highly uncertain, more observations are needed before the importance of water complexes can be accurately quantified.
On the propagation of low‐frequency fluctuations in the plasma sheet: 2. Characterization of the MHD eigenmodes and physical implications
Authors: Fruit G. , Louarn P. , Budnik E. , Sauvaud J. A. , Jacquey C. , Le Quéau D. , Rème H. , Lucek E. , Balogh A. , Cornilleau‐Wehrlin N.
Published: March 2004

In a first analysis of the low‐frequency fluctuations observed by Cluster during a crossing of the plasma sheet [Louarn et al., 2004], we identify oscillations that likely correspond to MHD eigenmodes. They are intense (10 nT), have a rather short period (20–25 s), have a wavelength of ∼5 Re, and are observed during an active period that follows a substorm onset. We show here that they combine both sausage and kink modes propagating in the x direction with a common spectral peak at ∼0.04 Hz, the sausage oscillations presenting also a secondary peak at 0.13 Hz. Using a complete theory of the linear MHD response of the plasma sheet, we reconstruct the sheet oscillations starting from given external perturbations. This method leads to quantitative predictions concerning the magnetic and pressure fluctuations. The existence of natural resonant frequencies of the sheet can indeed be foreseen and the relative weight of the kink‐like and sausage‐like modes can also be estimated. We show that the kink mode (0.04 Hz) and the high‐frequency sausage mode (0.14 Hz) are perfectly compatible with the MHD model of Harris sheet oscillations, with wavelength of ∼6 Re and ∼3 Re, respectively. The corresponding amplitude of the pressure and magnetic fluctuations also appears to be remarkably consistent with the theoretical predictions. Conversely, the low‐frequency sausage mode (0.04 Hz) is hardly explained by the MHD model. We propose that it could be a nonideal MHD or a kinetic mode, as the tearing mode.
Seasonal and interannual variations of the North Equatorial Current bifurcation in a high‐resolution OGCM
Authors: Kim Yoo Yin , Qu Tangdong , Jensen Tommy , Miyama Toru , Mitsudera Humio , Kang Hyoun‐Woo , Ishida Akio
Published: March 2004

The variation of the North Equatorial Current (NEC) bifurcation is investigated using results from a high‐resolution ocean general circulation model (OGCM). The bifurcation occurs at about 15.5°N for the annual average and is easily identifiable in the upper 500 m, but it varies with time and depth. In agreement with recent observations, during the summer season the NEC bifurcation moves equatorward with a weak poleward shift with depth, while a large poleward movement with a poleward shift with depth is found during the winter season. Vertical mode decomposition indicates that the seasonal variation of the NEC bifurcation is dominated by the first two baroclinic modes. On the interannual timescale, the meridional migration of the NEC bifurcation is strongly influenced by El Niño/Southern Oscillation (ENSO); its correlation with the Southern Oscillation Index exceeds 0.8 in magnitude at depths around the thermocline. The NEC bifurcation occurs at its northernmost position during El Niño years and at its southernmost position during La Niña years. This variation is mainly accounted for by westward propagation of upwelling (downwelling) Rossby waves generated by winds in the central equatorial Pacific and by an anomalous anticyclone (cyclone) located in the western North Pacific when a warm (cold) event matures. The interannual variability of the NEC transport is highly correlated with that of the Mindanao Current (MC) and the Kuroshio transports. It is also found that the interannual variability of the NEC bifurcation latitude is highly correlated with the variations of transports in the NEC and the Kuroshio, but is less correlated with transport variations in the MC.
Shallow water modeling of Antarctic Bottom Water crossing the equator
Authors: Choboter Paul F. , Swaters Gordon E.
Published: March 2004

The dynamics of abyssal equator‐crossing flows are examined by studying simplified models of the flow in the equatorial region in the context of reduced‐gravity shallow water theory. A simple “frictional geostrophic” model for one‐layer cross‐equatorial flow is described, in which geostrophy is replaced at the equator by frictional flow down the pressure gradient. This model is compared via numerical simulations to the one‐layer reduced‐gravity shallow water model for flow over realistic equatorial Atlantic Ocean bottom topography. It is argued that nonlinear advection is important at key locations where it permits the current to flow against a pressure gradient, a mechanism absent in the frictional geostrophic model and one of the reasons this model predicts less cross‐equatorial flow than the shallow water model under similar conditions. Simulations of the shallow water model with an annually varying mass source reproduce the correct amplitude of observed time variability of cross‐equatorial flow. The time evolution of volume transport across specific locations suggests that mass is stored in an equatorial basin, which can reduce the amplitude of time dependence of fluid actually proceeding into the Northern Hemisphere as compared to the amount entering the equatorial basin. Observed time series of temperature data at the equator are shown to be consistent with this hypothesis.
Space‐based diagnosis of surface ozone sensitivity to anthropogenic emissions
Authors: Martin Randall V. , Fiore Arlene M. , Van Donkelaar Aaron
Published: March 2004

We present a novel capability in satellite remote sensing with implications for air pollution control strategy. We show that the ratio of formaldehyde columns to tropospheric nitrogen dioxide columns is an indicator of the relative sensitivity of surface ozone to emissions of nitrogen oxides (NOx ≡ NO + NO2) and volatile organic compounds (VOCs). The diagnosis from these space‐based observations is highly consistent with current understanding of surface ozone chemistry based on in situ observations. The satellite‐derived ratios indicate that surface ozone is more sensitive to emissions of NOx than of VOCs throughout most continental regions of the Northern Hemisphere during summer. Exceptions include Los Angeles and industrial areas of Germany. A seasonal transition occurs in the fall when surface ozone becomes less sensitive to NOx and more sensitive to VOCs.
An estimate of motion between the spin axis and the hotspots over the past century
Authors: Argus Donald F. , Gross Richard S.
Published: March 2004

Estimates of the motion of the spin axis over the past century either neglect plate motion or are relative to the mean lithosphere. To understand the response of the spin axis to mass changes, it is more useful to estimate spin axis motion relative to the hotspots because the hotspots well represent the solid earth. The hotspots originate in the lower mantle, which comprises 2/3 of the earth's volume. Relative to the lower mantle the plates and the upper mantle move in opposite directions, to a large extent canceling each other out. The mean lithosphere moves quickly relative to the hotspots and poorly represents the solid earth. The spin axis has moved relative to the hotspots over the past century along the 68.4°W meridian at 4.03 milliarcsecond/yr. This motion is 11° counterclockwise of, 0.5 milliarcsecond/yr faster than, and 25% different than spin axis motion relative to the mean lithosphere.
Hepatitis C virus induces a mutator phenotype: Enhanced mutations of immunoglobulin and protooncogenes
Authors: Machida Keigo , Cheng Kevin T.-N. , Sung Vicky M.-H. , Shimodaira Shigetaka , Lindsay Karen L. , Levine Alexandra M. , Lai Ming-Yang , Lai Michael M. C.
Published: March 2004

Hepatitis C virus (HCV) is a nonretroviral oncogenic RNA virus, which is frequently associated with hepatocellular carcinoma (HCC) and B cell lymphoma. We demonstrated here that acute and chronic HCV infection caused a 5- to 10-fold increase in mutation frequency in Ig heavy chain,BCL-6,p53, and β-cateningenes ofin vitroHCV-infected B cell lines and HCV-associated peripheral blood mononuclear cells, lymphomas, and HCCs. The nucleotide-substitution pattern ofp53and β-cateninwas different from that of Ig heavy chain in HCV-infected cells, suggesting two different mechanisms of mutation. In addition, the mutated protooncogenes were amplified in HCV-associated lymphomas and HCCs, but not in lymphomas of nonviral origin or HBV-associated HCC. HCV induced error-prone DNA polymerase ζ, polymerase ι, and activation-induced cytidine deaminase, which together, contributed to the enhancement of mutation frequency, as demonstrated by the RNA interference experiments. These results indicate that HCV induces a mutator phenotype and may transform cells by a hit-and-run mechanism. This finding provides a mechanism of oncogenesis for an RNA virus.
Disruption of neural signal transducer and activator of transcription 3 causes obesity, diabetes, infertility, and thermal dysregulation
Authors: Gao Qian , Wolfgang Michael J. , Neschen Susanne , Morino Katsutaro , Horvath Tamas L. , Shulman Gerald I. , Fu Xin-Yuan
Published: March 2004

Signal transducer and activator of transcription (STAT)3 is widely expressed in the CNS during development and adulthood. STAT3 has been implicated in the control of neuron/glial differentiation and leptin-mediated energy homeostasis, but the physiological role and degree of involvement of STAT3 in these processes is not defined and controversial because of the lack of a direct genetic model. To address this, we created mice with a neural-specific disruption of STAT3 (STAT3
N-/-
). Surprisingly, homozygous mutants were born at the expected Mendelian ratio without apparent developmental abnormalities but susceptible to neonatal lethality. Mutants that survived the neonatal period were hyperphagic, obese, diabetic, and infertile. Administering a melanocortin-3/4 receptor agonist abrogated the hyperphagia and hypothalamic immunohistochemistry showed a marked reduction in proopiomelanocortin with an increase in neuropeptide Y and agouti-related protein. Mutants had reduced energy expenditure and became hypothermic after fasting or cold stress. STAT3
N-/-
mice are hyperleptinemic, suggesting a leptin-resistant condition. Concomitant with neuroendocrine defects such as decreased linear growth and infertility with accompanying increased corticosterone levels, this CNS knockout recapitulates the unique phenotype of
db
/
db
and
ob
/
ob
obese models and distinguishes them from other genetic models of obesity. Thus, STAT3 in the CNS plays essential roles in the regulation of energy homeostasis and reproduction.
DAXX interacts with heat shock factor 1 during stress activation and enhances its transcriptional activity
Authors: Boellmann Frank , Guettouche Toumy , Guo Yongle , Fenna Mary , Mnayer Laila , Voellmy Richard
Published: March 2004

DAXX, a modulator of apoptosis and a repressor of basal transcription, was identified in a two-hybrid screen as a protein capable of interacting with a trimeric form of human heat shock factor 1 (HSF1). In human cells, DAXX interacted with HSF1 essentially only during stress, i.e., when factor trimerization occurred. Several lines of experimentation suggested that DAXX is an important mediator of HSF1 activation: (
i
) overexpression of DAXX enhanced basal transactivation competence of HSF1 in the absence of a stress; (
ii
) a DAXX fragment exerted dominant-negative effects on HSF1 activation by different types of stress; (
iii
) induction of heat shock or stress protein (HSP)70 by heat stress was defective in a cell line lacking functional DAXX; and (
iv
) RNA interference depletion of DAXX also substantially reduced heat induction of HSF1 activity and HSP70 expression. HSF1 transactivation competence is repressed by an HSP90-containing multichaperone complex that interacts with trimeric factor. Overexpressed HSF1, known to be largely trimeric, only marginally increased HSF1 activity on its own but potentiated the activating effect of DAXX overexpression. Expression of a nonnative protein capable of competing for multichaperone complex also synergistically enhanced activation of HSF1 by DAXX. These observations suggest a model in which DAXX released from its nuclear stores during stress opposes repression of HSF1 transactivation competence by multichaperone complex through its interaction with trimerized HSF1. Our identification of DAXX as a mediator of HSF1 activation raises the question whether DAXX produces some of its pleiotropic effects through modulation of HSP levels.