bluuebunny/crossref_metadata_2025 huggingface dataset:
Flipping the wound that doesn't heal: the upside of coagulation in cancer
Authors: Teicher Beverly A.
Published: May 2009

Two mechanisms for targeting tumor vasculature are well recognized: antiangiogenesis and vascular disruption. In this issue of Blood, Bieker and colleagues take therapeutic advantage of coagulation and add a third mechanism, vascular infarction, to this group by demonstrating the effect through first-in-man administration of tTF-NGR.
Complete sequence determination of a novel reptile iridovirus isolated from soft-shelled turtle and evolutionary analysis of Iridoviridae
Authors: Huang Youhua , Huang Xiaohong , Liu Hong , Gong Jie , Ouyang Zhengliang , Cui Huachun , Cao Jianhao , Zhao Yingtao , Wang Xiujie , Jiang Yulin , Qin Qiwei
Published: May 2009

Background

Soft-shelled turtle iridovirus (STIV) is the causative agent of severe systemic diseases in cultured soft-shelled turtles (Trionyx sinensis). To our knowledge, the only molecular information available on STIV mainly concerns the highly conserved STIV major capsid protein. The complete sequence of the STIV genome is not yet available. Therefore, determining the genome sequence of STIV and providing a detailed bioinformatic analysis of its genome content and evolution status will facilitate further understanding of the taxonomic elements of STIV and the molecular mechanisms of reptile iridovirus pathogenesis.

Results

We determined the complete nucleotide sequence of the STIV genome using 454 Life Science sequencing technology. The STIV genome is 105 890 bp in length with a base composition of 55.1% G+C. Computer assisted analysis revealed that the STIV genome contains 105 potential open reading frames (ORFs), which encode polypeptides ranging from 40 to 1,294 amino acids and 20 microRNA candidates. Among the putative proteins, 20 share homology with the ancestral proteins of the nuclear and cytoplasmic large DNA viruses (NCLDVs). Comparative genomic analysis showed that STIV has the highest degree of sequence conservation and a colinear arrangement of genes with frog virus 3 (FV3), followed by Tiger frog virus (TFV), Ambystoma tigrinum virus (ATV), Singapore grouper iridovirus (SGIV), Grouper iridovirus (GIV) and other iridovirus isolates. Phylogenetic analysis based on conserved core genes and complete genome sequence of STIV with other virus genomes was performed. Moreover, analysis of the gene gain-and-loss events in the family Iridoviridae suggested that the genes encoded by iridoviruses have evolved for favoring adaptation to different natural host species.

Conclusion

This study has provided the complete genome sequence of STIV. Phylogenetic analysis suggested that STIV and FV3 are strains of the same viral species belonging to the Ranavirus genus in the Iridoviridae family. Given virus-host co-evolution and the phylogenetic relationship among vertebrates from fish to reptiles, we propose that iridovirus might transmit between reptiles and amphibians and that STIV and FV3 are strains of the same viral species in the Ranavirus genus.
The CD-loop of PAI-2 (SERPINB2) is redundant in the targeting, inhibition and clearance of cell surface uPA activity
Authors: Cochran Blake J , Gunawardhana Lakshitha P , Vine Kara L , Lee Jodi A , Lobov Sergei , Ranson Marie
Published: May 2009

Background

Plasminogen activator inhibitor type-2 (PAI-2, SERPINB2) is an irreversible, specific inhibitor of the urokinase plasminogen activator (uPA). Since overexpression of uPA at the surface of cancer cells is linked to malignancy, targeting of uPA by exogenous recombinant PAI-2 has been proposed as the basis of potential cancer therapies. To this end, reproducible yields of high purity protein that maintains this targeting ability is required. Herein we validate the use in vitro of recombinant 6 × His-tagged-PAI-2 lacking the intrahelical loop between C and D alpha-helices (PAI-2 ΔCD-loop) for these purposes.

Results

We show that PAI-2 ΔCD-loop expressed and purified from the pQE9 vector system presents an easier purification target than the previously used pET15b system. Additionally, PAI-2 ΔCD-loop gave both higher yield and purity than wild-type PAI-2 expressed and purified under identical conditions. Importantly, absence of the CD-loop had no impact on the inhibition of both solution phase and cell surface uPA or on the clearance of receptor bound uPA from the cell surface. Furthermore, uPA:PAI-2 ΔCD-loop complexes had similar binding kinetics (KD ~5 nM) with the endocytosis receptor Very Low Density Lipoprotein Receptor (VLDLR) to that previously published for uPA:PAI-2 complexes.

Conclusion

We demonstrate that the CD-loop is redundant for the purposes of cellular uPA inhibition and cell surface clearance (endocytosis) and is thus suitable for the development of anti-uPA targeted cancer therapeutics.
The use of herbal medicines by people with cancer: a qualitative study
Authors: Gratus Christine , Wilson Sue , Greenfield Sheila M , Damery Sarah L , Warmington Sally A , Grieve Robert , Steven Neil M , Routledge Philip
Published: May 2009

Background

Between 7% and 48% of cancer patients report taking herbal medicines after diagnosis. Because of the possibility of unwanted side effects or interactions with conventional treatments, people with cancer are generally advised to tell the professionals treating them if they are taking any form of medication, including herbal medicines and supplements. Studies suggest that only about half do so and that the professionals themselves have at best very limited knowledge and feel unable to give informed advice. This study is intended to inform the future development of information resources for cancer patients, survivors and healthcare professionals including tools for use before or during consultation to make it easier for patients to mention, and for healthcare professionals to ask about, use of herbal medications.

Methods/design

This is a three-phase study. In phase 1, a systematic review of the literature on self-medication with herbal medicines among UK populations living with cancer will establish the current evidence base on use of herbal medicine, sources of information, characteristics and motivations. This will allow us to better understand what aspects need further investigation and inform the topic guide for a qualitative study (phase 2). Six focus groups of six to eight cancer patients who have used at least one herbal preparation since diagnosis will explore behaviour, beliefs, knowledge, information sources and needs in an informal conversational setting.

Informed by the findings of the systematic review and qualitative study, in phase 3 we will construct and pilot a questionnaire for a future large-scale survey to quantify and prioritise people's beliefs, needs and information preferences.

Discussion

Despite known interactions with conventional cancer treatments and contraindications for some herbal remedies with specific cancers, reliable information resources for patients are very limited. Identifying cancer patients' information needs and preferences is the first step in creating a suitable resource for both the public and the professionals advising them.
Influence of human chorionic gonadotropin (hCG) on in vitro growth of Plasmodium falciparum
Authors: Pong Clinton K , Thévenon Audrey Davidson , Zhou James Ainong , Taylor Diane Wallace
Published: May 2009

Background

During pregnancy, women are more susceptible to Plasmodium falciparum infections and frequently have a higher parasitaemia than non-pregnant women. Several mechanisms are responsible for their increased susceptibility, including down-modulation of immune responses that aid in parasite clearance and sequestration of infected erythrocytes in the placenta. Early in pregnancy, a third mechanism may contribute to higher parasitaemia, since it has been reported that addition of human chorionic gonadotropin (hCG) to in vitro cultures of the NF54-strain of P. falciparum results in increased parasite growth rates. The goal of this study was to further examine the effect of hCG on P. falciparum growth.

Methods

The NF54-3D7, FVO and 7G8 strains of P. falciparum were cultured in vitro with various physiological concentrations of hCG purchased from three sources. Infected erythrocytes were also co-cultured with a human cell line that naturally secretes hCG.

Results

Results from 14 experiments using different combinations of parasite strains and concentrations of hCG from different sources, as well as the co-culture studies, failed to provide convincing evidence that hCG enhances parasite growth in vitro.

Conclusion

Based on these data, it seems unlikely that hCG has a direct effect on the rate of parasite growth early in pregnancy.
Bioactivity-guided identification and cell signaling technology to delineate the immunomodulatory effects of Panax ginseng on human promonocytic U937 cells
Authors: Lee Davy CW , Yang Cindy LH , Chik Stanley CC , Li James CB , Rong Jian-hui , Chan Godfrey CF , Lau Allan SY
Published: May 2009

Background

Ginseng is believed to have beneficial effects against human diseases, and its active components, ginsenosides, may play critical roles in its diverse physiological actions. However, the mechanisms underlying ginseng's effects remain to be investigated. We hypothesize some biological effects of ginseng are due to its anti-inflammatory effects.

Methods

Human promonocytic U937 cells were used to investigate the immunomodulatory effects of ginseng following TNF-α treatment. A global gene expression profile was obtained by using genechip analysis, and specific cytokine expression was measured by quantitative RT-PCR and ELISA. HPLC was used to define the composition of ginsenosides in 70% ethanol-water extracts of ginseng. Activation of signalling kinases was examined by Western blot analysis.

Results

Seventy percent ethanol-water extracts of ginseng significantly inhibited the transcription and secretion of CXCL-10 following TNF-α stimulation. Nine ginsenosides including Rb1, Rb2, Rc, Rd, Re, Rf, Rg1, Rg3and Rh1were identified in our extract by HPLC. Seven out of nine ginsenosides could significantly inhibit TNF-α-induced CXCL-10 expression in U937 cells and give comparable inhibition of CXCL-10 transcription to those with the extract. However, the CXCL-10 suppressive effect of individual ginsenosides was less than that of the crude extract or the mixture of ginsenosides. The CXCL-10 suppression can be correlated with the inactivation of ERK1/2 pathways by ginseng.

Conclusion

We showed ginseng suppressed part of the TNF-α-inducible cytokines and signalling proteins in promonocytic cells, suggesting that it exerts its anti-inflammatory property targeting at different levels of TNF-α activity. The anti-inflammatory role of ginseng may be due to the combined effects of ginsenosides, contributing in part to the diverse actions of ginseng in humans.
Detection of hepatitis E virus in wild boars of rural and urban regions in Germany and whole genome characterization of an endemic strain
Authors: Schielke Anika , Sachs Katja , Lierz Michael , Appel Bernd , Jansen Andreas , Johne Reimar
Published: May 2009

Background

Hepatitis E is an increasingly diagnosed human disease in Central Europe. Besides domestic pigs, in which hepatitis E virus (HEV) infection is highly prevalent, wild boars have been identified as a possible source of human infection. In order to assess the distribution of HEV in the wild boar population of Germany, we tested liver samples originating from different geographical regions for the presence of the HEV genome and compared the detected sequences to animal and human HEV strains.

Results

A total of 148 wild boar liver samples were tested using real-time RT-PCR resulting in an average HEV detection rate of 14.9% (95% CI 9.6–21.6). HEV was detected in all age classes and all geographical regions. However, the prevalence of HEV infection was significantly higher in rural as compared to urban regions (p < 0.001). Sequencing of the PCR products indicated a high degree of heterogenicity of the detected viruses within genotype 3 and a grouping according to their geographical origin. The whole genome sequence of an HEV isolate (wbGER27) detected in many wild boars in the federal state of Brandenburg was determined. It belongs to genotype 3i and shows 97.9% nucleotide sequence identity to a partial sequence derived from a human hepatitis E patient from Germany.

Conclusion

The results indicate that wild boars have to be considered as a reservoir for HEV in Germany and that a risk of HEV transmission to humans is present in rural as well as urban regions.
Validation of the International Classification of Functioning, Disability and Health Core Set for chronic widespread pain from the perspective of fibromyalgia patients
Authors: Hieblinger Robin , Coenen Michaela , Stucki Gerold , Winkelmann Andreas , Cieza Alarcos
Published: May 2009

Introduction

Functioning is recognized as an important study outcome in chronic widespread pain (CWP). The Comprehensive ICF Core Set for CWP is an application of the International Classification of Functioning, Disability and Health (ICF) with the purpose of representing the typical spectrum of functioning of patients with CWP. The objective of the study was to add evidence to the validation of the Comprehensive ICF Core Set for CWP from the patient perspective. The specific aims were to explore the aspects of functioning and health important to patients with fibromyalgia, and to examine to what extent these aspects are represented by the current version of the Comprehensive ICF Core Set for CWP.

Methods

The sampling of patients followed the maximum variation strategy. Sample size was determined by saturation. The focus groups were digitally recorded and transcribed verbatim. The meaning condensation procedure was used for qualitative data analysis. After qualitative data analysis, the identified concepts were linked to ICF categories.

Results

Thirty-three patients participated in six focus groups. Fifty-four ICF categories out of 67 categories of the Comprehensive ICF Core Set for CWP were reported by the patients. Forty-eight additional categories that are not covered in the Comprehensive ICF Core Set for CWP were raised.

Conclusions

Most ICF categories of the existing version of the Comprehensive ICF Core Set for CWP could be confirmed from the patient perspective. However, several categories not included in the Core Set emerged and should be considered for inclusion.
Gene expression and activity of cartilage degrading glycosidases in human rheumatoid arthritis and osteoarthritis synovial fibroblasts
Authors: Pásztói Mária , Nagy György , Géher Pál , Lakatos Tamás , Tóth Kálmán , Wellinger Károly , Pócza Péter , György Bence , Holub Marianna C , Kittel Ágnes , Pálóczy Krisztina , Mazán Mercédesz , Nyirkos Péter , Falus András , Buzas Edit I
Published: May 2009

Introduction

Similar to matrix metalloproteinases, glycosidases also play a major role in cartilage degradation. Carbohydrate cleavage products, generated by these latter enzymes, are released from degrading cartilage during arthritis. Some of the cleavage products (such as hyaluronate oligosaccharides) have been shown to bind to Toll-like receptors and provide endogenous danger signals, while others (like N-acetyl glucosamine) are reported to have chondroprotective functions. In the current study for the first time we systematically investigated the expression of glycosidases within the joints.

Methods

Expressions of β-D-hexosaminidase, β-D-glucuronidase, hyaluronidase, sperm adhesion molecule 1 and klotho genes were measured in synovial fibroblasts and synovial membrane samples of patients with rheumatoid arthritis and osteoarthritis by real-time PCR. β-D-Glucuronidase, β-D-glucosaminidase and β-D-galactosaminidase activities were characterized using chromogenic or fluorogenic substrates. Synovial fibroblast-derived microvesicles were also tested for glycosidase activity.

Results

According to our data, β-D-hexosaminidase, β-D-glucuronidase, hyaluronidase, and klotho are expressed in the synovial membrane. Hexosaminidase is the major glycosidase expressed within the joints, and it is primarily produced by synovial fibroblasts. HexA subunit gene, one of the two genes encoding for the alpha or the beta chains of hexosaminidase, was characterized by the strongest gene expression. It was followed by the expression of HexB subunit gene and the β-D-glucuronidase gene, while the expression of hyaluronidase-1 gene and the klotho gene was rather low in both synovial fibroblasts and synovial membrane samples. Tumor growth factor-β1 profoundly downregulated glycosidase expression in both rheumatoid arthritis and osteoarthritis derived synovial fibroblasts. In addition, expression of cartilage-degrading glycosidases was moderately downregulated by proinflammatory cytokines including TNFα, IL-1β and IL-17.

Conclusions

According to our present data, glycosidases expressed by synovial membranes and synovial fibroblasts are under negative regulation by some locally expressed cytokines both in rheumatoid arthritis and osteoarthritis. This does not exclude the possibility that these enzymes may contribute significantly to cartilage degradation in both joint diseases if acting in collaboration with the differentially upregulated proteases to deplete cartilage in glycosaminoglycans.
Cytomegalovirus infection in critically ill patients: a systematic review
Authors: Osawa Ryosuke , Singh Nina
Published: May 2009

Introduction

The precise role of cytomegalovirus (CMV) infection in contributing to outcomes in critically ill immunocompetent patients has not been fully defined.

Methods

Studies in which critically ill immunocompetent adults were monitored for CMV infection in the intensive care unit (ICU) were reviewed.

Results

CMV infection occurs in 0 to 36% of critically ill patients, mostly between 4 and 12 days after ICU admission. Potential risk factors for CMV infection include sepsis, requirement of mechanical ventilation, and transfusions. Prolonged mechanical ventilation (21 to 39 days vs. 13 to 24 days) and duration of ICU stay (33 to 69 days vs. 22 to 48 days) correlated significantly with a higher risk of CMV infection. Mortality rates in patients with CMV infection were higher in some but not all studies. Whether CMV produces febrile syndrome or end-organ disease directly in these patients is not known.

Conclusions

CMV infection frequently occurs in critically ill immunocompetent patients and may be associated with poor outcomes. Further studies are warranted to identify subsets of patients who are likely to develop CMV infection and to determine the impact of antiviral agents on clinically meaningful outcomes in these patients.
Cancer Care and Cancer Survivorship Care in the United States: Will We Be Able to Care for These Patients in the Future?
Authors: Shulman Lawrence N. , Jacobs Linda A. , Greenfield Sheldon , Jones Barbara , McCabe Mary S. , Syrjala Karen , Diller Lisa , Shapiro Charles L. , Marcus Alfred C. , Campbell Marci , Santacroce Sheila , Kagawa-Singer Marjorie , Ganz Patricia A.
Published: May 2009

The combination of a shortfall in oncologists and primary care physicians and an increased number of patients using more health care resources raises concerns about our health care system's ability to accommodate future patients with cancer and cancer survivors.
Quality of Care and Cancer Survivorship: The Challenge of Implementing the Institute of Medicine Recommendations
Authors: Ganz Patricia A.
Published: May 2009

As the population ages, maintaining the quality of care for new patients with cancer will be challenged by an anticipated shortage of health professionals to care for the increased number of newly diagnosed and surviving patients with cancer.
Treatment Summaries in Radiation Oncology and Their Role in Improving Patients' Quality of Care: Past, Present, and Future
Authors: Hayman James A.
Published: May 2009

Through treatment summaries, radiation oncologists can build upon past efforts and improve the future quality of care for all patients receiving treatment with radiation. This article looks at what treatment summaries should contain and how they might be improved.
Passport for Care: Implementing the Survivorship Care Plan
Authors: Horowitz Marc E. , Fordis Michael , Krause Susan , McKellar Julie , Poplack David G.
Published: May 2009

Approximately 12,000 children in the United States are diagnosed with cancer each year, and roughly 75% of these patients become long-term survivors. The Passport for Care was developed to support these survivors and their health care providers.
The Cancer Survivorship Care Plan: Health Care in the Context of Cancer
Authors: Feuerstein Michael
Published: May 2009

A 6-year cancer survivor shares how participating in the development of his cancer survivorship care plan yielded physical and emotional benefits, and laments that such plans are not more readily available.
Cancer Care and Survivorship Planning: Promises and Challenges
Authors: Lichtenfeld Len
Published: May 2009

Although we have made some progress in understanding long-term effects of some cancer treatments, there is still much more to learn about the impact of our treatments on our patients.
Ethical Issues Related to Patient Use of Complementary and Alternative Medicine
Authors: Jacobson Geraldine M. , Cain Joanna Mary
Published: May 2009

It is important for physicians to set aside their personal opinions and establish open lines of communication with patients about alternatives to conventional medical treatment.
Progress in the Control of Chemotherapy-Induced Emesis: New Agents and New Studies
Authors: Gralla Richard J. , Raftopoulos Harry
Published: May 2009

New agents and studies have demonstrated benefit in improving antiemetic therapy. Incorporating evidence-based guideline recommendations and appropriate emesis assessments are key components to achieving the best practice.
Evolutionary origins of blastoporal expression and organizer activity of the vertebrate gastrula organizer genelhx1and its ancient metazoan paraloglhx3
Authors: Yasuoka Yuuri , Kobayashi Masaaki , Kurokawa Daisuke , Akasaka Koji , Saiga Hidetoshi , Taira Masanori
Published: May 2009

Expression of the LIM homeobox gene lhx1 (lim1) is specific to the vertebrate gastrula organizer. Lhx1 functions as a transcriptional regulatory core protein to exert `organizer' activity in Xenopus embryos. Its ancient paralog, lhx3 (lim3),is expressed around the blastopore in amphioxus and ascidian, but not vertebrate, gastrulae. These two genes are thus implicated in organizer evolution, and we addressed the evolutionary origins of their blastoporal expression and organizer activity. Gene expression analysis of organisms ranging from cnidarians to chordates suggests that blastoporal expression has its evolutionary root in or before the ancestral eumetazoan for lhx1,but possibly in the ancestral chordate for lhx3, and that in the ascidian lineage, blastoporal expression of lhx1 ceased, whereas endodermal expression of lhx3 has persisted. Analysis of organizer activity using Xenopus embryos suggests that a co-factor of LIM homeodomain proteins, Ldb, has a conserved function in eumetazoans to activate Lhx1, but that Lhx1 acquired organizer activity in the bilaterian lineage,Lhx3 acquired organizer activity in the deuterostome lineage and ascidian Lhx3 acquired a specific transactivation domain to confer organizer activity on this molecule. Knockdown analysis using cnidarian embryos suggests that Lhx1 is required for chordin expression in the blastoporal region. These data suggest that Lhx1 has been playing fundamental roles in the blastoporal region since the ancestral eumetazoan arose, that it contributed as an`original organizer gene' to the evolution of the vertebrate gastrula organizer, and that Lhx3 could be involved in the establishment of organizer gene networks.
Myosin II regulates extension, growth and patterning in the mammalian cochlear duct
Authors: Yamamoto Norio , Okano Takayuki , Ma Xuefei , Adelstein Robert S. , Kelley Matthew W.
Published: May 2009

The sensory epithelium of the mammalian cochlea comprises mechanosensory hair cells that are arranged into four ordered rows extending along the length of the cochlear spiral. The factors that regulate the alignment of these rows are unknown. Results presented here demonstrate that cellular patterning within the cochlea, including the formation of ordered rows of hair cells,arises through morphological remodeling that is consistent with the mediolateral component of convergent extension. Non-muscle myosin II is shown to be expressed in a pattern that is consistent with an active role in cellular remodeling within the cochlea, and genetic or pharmacological inhibition of myosin II results in defects in cellular patterning that are consistent with a disruption in convergence and extension. These results identify the first molecule, myosin II, which directly regulates cellular patterning and alignment within the cochlear sensory epithelium. Our results also provide insights into the cellular mechanisms that are required for the formation of highly ordered cellular patterns.
Multiple roles of β-catenin in controlling the neurogenic niche for midbrain dopamine neurons
Authors: Tang Mianzhi , Miyamoto Yasunori , Huang Eric J.
Published: May 2009

Stem cell-based replacement therapy has emerged as a potential strategy to alleviate specific features of movement disorder in Parkinson's disease. However, the current strategy to produce dopamine (DA) neurons from embryonic stem cells has many limitations, including the difficulty of generating DA neurons with high yields. Further insights into the mechanisms that control the neurogenesis of DA neurons will reduce or mitigate such limitations. It is well established that the ventral midbrain (vMB) contains the neurogenic niche that produces DA neurons. However, it is unclear how the microenvironment within this niche controls DA neurogenesis. Here, we show that β-catenin controls DA neurogenesis by maintaining the integrity of the neurogenic niche and the progression from progenitors to DA neurons. Using conditional gene targeting approaches, we show that regional deletion of β-catenin in the vMB by using Shh-Cre disrupts adherent junctions of progenitors and the integrity of radial glia in the vMB, which leads to a severe reduction in DA neurogenesis and perturbs the migration and segregation of DA neurons. By contrast, Th-IRES-Cre removes β-catenin in a subset of neural progenitor cells without perturbing the cellular and structural integrity of the vMB. Interestingly, loss of β-catenin in Th-IRES-Cre;β-Ctnfl/fl mutants negatively regulates neurogenesis by interfering with the progression of committed progenitors to DA neurons. Taken together, these results provide new insights into the indispensable functions of β-catenin at multiple stages during DA neurogenesis. They also suggest that β-catenin-mediated signaling pathways can be targeted to promote and expand DA neurons in cell-based therapeutic strategies.
Interplay between activin and Hox genes determines the formation of the kidney morphogenetic field
Authors: Preger-Ben Noon Ella , Barak Hila , Guttmann-Raviv Noga , Reshef Ram
Published: May 2009

The kidney develops in a specific position along the anterior-posterior axis. All vertebrate kidney tissues are derived from the intermediate mesoderm(IM), and early kidney genes such as Lim1 and Pax2 are expressed in amniotes posterior to the sixth somite axial level. IM cells anterior to this level do not express kidney genes owing to changes in their competence to respond to kidney-inductive signals present along the entire axis. We aimed to understand the molecular mechanisms governing the loss of competence of anterior IM cells and the formation of the anterior border of the kidney morphogenetic field. We identified the dorsal neural tube as the potential kidney-inductive tissue and showed that activin, a secreted morphogen, is necessary but insufficient for Lim1 induction and establishment of the kidney field. Activin or activin-like and BMP signaling cascades are activated along the entire axis, including in anterior non-kidney IM, suggesting that competence to respond to these signals involves downstream or other components. Detailed expression pattern analysis of Hox genes during early chick development revealed that paralogous group four genes share the same anterior border as the kidney genes. Ectopic expression of Hoxb4in anterior non-kidney IM, either by retinoic acid (RA) administration or plasmid-mediated overexpression, resulted in ectopic kidney gene expression. The anterior expansion of Lim1 expression was restrained when Hoxb4 was co-expressed with a truncated form of activin receptor. We suggest a model in which the competence of IM cells to respond to TGFβsignaling and express kidney genes is driven by RA and mediated by Hoxb4.
Quantitative Evaluation of Glycyrrhizic Acid That Affects the Product Quality of Kakkonto Extract, a Traditional Herbal Medicine, by a Chemometric near Infrared Spectroscopic Method
Authors: Mohri Yoshifumi , Sakata Yukoh , Otsuka Makoto
Published: May 2009

The purpose of this study was to construct a calibration model for the prediction of glycyrrhizic acid content in Kakkonto extracts using near infrared (NIR) spectroscopy. The NIR spectra of the Kakkonto extracts were obtained using a Fourier transform NIR spectrometer in transmission mode and chemometric analysis was performed using partial least-square (PLS) regression. The calibration model was constructed by the selection of wave number regions and by the first derivative pre-treatment of NIR spectra. The glycyrrhizic acid content could be predicted using a calibration model comprising three principal components (PCs) obtained by the PLS method. The calibration model was theoretically analysed by investigating the standard error of prediction values, the loading vectors of each PC and the regression vector. The relationship between the actual and predicted glycyrrhizic acid contents in the Kakkonto extract exhibited a straight line with a coefficient of determination of 0.966 (calibration) and 0.945 (validation), respectively. The predicted glycyrrhizic acid content in the Kakkonto extract was within the 95% predictive intervals.
NOPAPROD Non-Parametric Testing on Projections from Multivariate Data. Applications to near Infrared Spectroscopy in Clinical Studies
Authors: Nyström Josefina , Lindholm-Sethson Britta , Geladi Paul
Published: May 2009

Clinical studies may be carried out using non-invasively collected near infrared spectra of patient skin. Two problems encountered are: (1) data reduction to go from thousands of wavelengths to some clinically relevant estimator and (2) getting statistical significance from noisy data with sometimes very skewed distributions. The problem of data reduction can usually be solved by principal component analysis to get a few meaningful components. In the space spanned by these components, a direction of discrimination may have to be found, typically discrimination between treated and control. A visual difference in a score plot is often not enough; statistical significance has to be demonstrated. Once a univariate estimator is found, non-parametric testing can show significant differences, even if the data are noisy and have an unknown and skewed distribution. The NOPRAPOD method com bines the actions of finding a direction in a reduced data space and performing the non-parametric significance testing by producing a disk of significance. Two examples are included. Example one is from a study of diabetes-related neuropathy where it is shown that significant differences show up in the NIR spectra. Example two is from a study of post-operative radiation treatment of breast cancer patients, where it is shown that radiation effects (erythema) and the effect of lotion can be determined with an indication of significance from the NIR spectra.
Three Novel CFTR Polymorphic Repeats Improve Segregation Analysis for Cystic Fibrosis
Authors: Elce Ausilia , Boccia Angelo , Cardillo Giuseppe , Giordano Sonia , Tomaiuolo Rossella , Paolella Giovanni , Castaldo Giuseppe
Published: May 2009

Background: Molecular diagnosis for cystic fibrosis (CF) is based on the direct identification of mutations in the CFTR gene [cystic fibrosis transmembrane conductance regulator (ATP-binding cassette sub-family C, member 7)] (detection rate about 90% with scanning procedures) and on segregation analysis of intragenic polymorphisms for carrier and prenatal diagnosis in about 20% of CF families in which 1 or both causal mutations are unknown.

Methods: We identified 3 novel intragenic polymorphic repeats (IVS3polyA, IVS4polyA, and IVS10CA repeats) in the CFTR gene and developed and validated a procedure based on the PCR followed by capillary electrophoresis for large-scale analysis of these polymorphisms and the 4 previously identified microsatellites (IVS1CA, IVS8CA, IVS17bTA, and IVS17bCA repeats) in a single run. We validated the procedure for both single- and 2-cell samples (for a possible use in preimplantation diagnosis), and on a large number of CF patients bearing different genotypes and non-CF controls.

Results: The allelic distribution and heterozygosity results suggest that the 3 novel polymorphisms strongly contribute to carrier and prenatal diagnosis of CF in families in which 1 or both causal mutations have not been identified. At least 1 of the 4 previously identified microsatellites was informative in 78 of 100 unrelated CF families; at least 1 of all 7 polymorphisms was informative in 98 of the families. Finally, the analysis of haplotypes for the 7 polymorphisms revealed that most CF mutations are associated with different haplotypes, suggesting multiple slippage events but a single origin for most CFTR mutations.

Conclusions: The analysis of the 7 polymorphisms is a rapid and efficient tool for routine carrier, prenatal, and preimplantation diagnosis of CF.
Revisiting journalism as a profession in the 19th century: Empirical findings on women journalists in Central Europe
Authors: Kinnebrock Susanne
Published: May 2009

This contribution raises the question whether journalism at its beginnings was indeed a profession only for men, as much of the research literature suggests. However, the assumption of a “gendered profession” may also be due to gendered research patterns that produce and reproduce a gendered academic discourse on journalism. The study presented here puts these questions to test and investigates the cultural, social and work-related position of female writers in German-speaking countries at the end of the 19th century. The data is based on a complete census collected between 1896 and 1898. In a second step, the occupation and opus of female writers who worked for periodicals will be analyzed along established concepts of journalism in order to illustrate how women are systematically excluded by dominant concepts of what journalism is and journalists actually do.
News for adolescents: Mission impossible? An evaluation of Flemish television news aimed at teenagers
Authors: Vandebosch Heidi , Dhoest Alexander , Van den Bulck Hilde
Published: May 2009

Media companies as well as governments launch initiatives to reverse the decline in news consumption by adolescents. Since 2007, the Flemish government has been funding newscasts for adolescents on two commercial channels, Zoom on VTM and Jam on VT4. In 2008, these programs were evaluated using in-depth interviews with producers, content analysis of 30 episodes of each program, an analysis of the ratings for the first season, and an online survey among 663 adolescents aged 10 to 18. Results indicate that there is a lot of variation within this group, making it hard to please them with a single program. Zoom addresses slightly older adolescents (12–18) with a program closely following the “adult” news, while Jam provides younger adolescents (10–16) with more digestible and entertaining news. Most respondents in the survey liked both programs, among other things because of the strong presence of adolescents on screen. Yet adolescent viewing figures are extremely low, mainly due to the inappropriate place in the schedule.
D3 GH receptor polymorphism is not associated with IGF1 levels in untreated acromegaly
Authors: Kamenicky Peter , Dos Santos Christine , Espinosa Consuelo , Salenave Sylvie , Galland Françoise , Le Bouc Yves , Maison Patrick , Bougnères Pierre , Chanson Philippe
Published: May 2009

Context

A discrepancy between serum GH and IGF1 concentrations is frequent in patients with acromegaly. Here, we examined whether the exon 3-deleted (d3) GH receptor (GHR) variant, which has been linked to increased responsiveness to GH treatment in short children, influences the GH/IGF1 relationship in patients with acromegaly.

Objective

To study the possible influence of the GHR genotype on the GH/IGF1 relationship in untreated acromegalic patients.

Design

GHR genotype analysis with retrospective clinical and biochemical data collection performed in a single third-reference medical center.

Patients and methods

Clinical data were obtained from the medical records of 105 acromegalic patients who had GH and IGF1 assays in the same laboratory and who were genotyped for the full-length (fl) or d3-GHR alleles.

Results

The distribution of GHR genotypes was 51% fl/fl, 30% fl/d3, and 19% d3/d3. Patients with d3/d3 genotype were younger than the patients in the other two groups (P<0.05). Baseline GH and IGF1 concentrations did not differ among the three groups. The linear correlation between GH and IGF1 concentrations was similar in the three genotypic groups.

Conclusions

The exon 3 GHR genotype does not affect the GH/IGF1 relationship in untreated acromegalic patients with high circulating GH and IGF1 levels.
The spectrum of phenotypes associated with mutations in steroidogenic factor 1 (SF-1, NR5A1, Ad4BP) includes severe penoscrotal hypospadias in 46,XY males without adrenal insufficiency
Authors: Köhler Birgit , Lin Lin , Mazen Inas , Cetindag Cigdem , Biebermann Heike , Akkurt Ilker , Rossi Rainer , Hiort Olaf , Grüters Annette , Achermann John C
Published: May 2009

Objective

Hypospadias is a frequent congenital anomaly but in most cases an underlying cause is not found. Steroidogenic factor 1 (SF-1, NR5A1, Ad4BP) is a key regulator of human sex development and an increasing number of SF-1 (NR5A1) mutations are reported in 46,XY disorders of sex development (DSD). We hypothesized that NR5A1 mutations could be identified in boys with hypospadias.

Design and methods

Mutational analysis of NR5A1 in 60 individuals with varying degrees of hypospadias from the German DSD network.

Results

Heterozygous NR5A1 mutations were found in three out of 60 cases. These three individuals represented the most severe end of the spectrum studied as they presented with penoscrotal hypospadias, variable androgenization of the phallus and undescended testes (three out of 20 cases (15%) with this phenotype). Testosterone was low in all three patients and inhibin B/anti-Müllerian hormone (AMH) were low in two patients. Two patients had a clear male gender assignment. Gender re-assignment to male occurred in the third case. Two patients harbored heterozygous nonsense mutations (p.Q107X/WT, p.E11X/WT). One patient had a heterozygous splice site mutation in intron 2 (c.103-3A/WT) predicted to disrupt the main DNA-binding motif. Functional studies of the nonsense mutants showed impaired transcriptional activation of an SF-1-responsive promoter (Cyp11a). To date, adrenal insufficiency has not occurred in any of the patients.

Conclusions

SF-1 (NR5A1) mutations should be considered in 46,XY individuals with severe (penoscrotal) hypospadias, especially if undescended testes, low testosterone, or low inhibin B/AMH levels are present. SF-1 mutations in milder forms of idiopathic hypospadias are unlikely to be common.
Effect of low-dose mifepristone administration on day 2 after ovulation on transcript profiles in implantation-stage endometrium of rhesus monkeys
Authors: Ghosh D , Sharkey A M , Charnock-Jones D S , Smith S K , Sengupta Jayasree
Published: May 2009

Progesterone is essential for endometrial receptivity in primates. In studies previously performed using global gene profiling based on microarray technology, attempts have been made to identify changes in gene expression between early luteal-phase and mid-luteal-phase endometria. However, the issue of the putative impact of preimplantation embryo-derived signal in the process of endometrial receptivity was missing in the previous studies. In the present study, an attempt has been made to delineate the transcripts profile in implantation-stage endometrium under combinatorial regulation of progesterone and embryo-derived signal in the rhesus monkey. To this effect, we have compared transcript profiles for 409 known genes between control receptive stage (n=13), and mifepristone-induced desynchronized and non-receptive stage (n=12) monkey endometrial samples collected on days 4 (n=12) and 6 (n=13) after ovulation from mated, potential conception cycles, using cDNA arrays containing sequence-verified clones. Statistical analysis of correlation of estimated transcript abundance between arrays and qRT-PCR for nine selected gene products yielded significant (P<0.05) concordance. Of 409 genes, a total of 40 gene transcripts were seen to be affected, nine gene transcripts in endometrial samples were found to progressively increase between days 4 and 6 following mifepristone treatment, while an additional five genes showed differential expression profile depending on the day after treatment. Additionally, different sets of 12 and 14 gene products showed changes in days 4 and 6 post-ovulation samples respectively. A new cohort of 28 gene products in implantation-stage endometrium was seen to be affected by luteal-phase mifepristone.
Observations Concerning Reproductive Temperature Requirements of Captive Lahontan Cutthroat Trout
Authors: Bigelow John P , Rauw Wendy M , Gomez-Raya Luis
Published: May 2009

The effects of holding temperature during late oocyte development and spawning on the timing of ovulation, fecundity, and egg survival in female Lahontan cutthroat trout Oncorhynchus clarkii henshawi in three postovulatory regimes were investigated. The timing of ovulation was similar for females held at 7.2°C and 12.4°C from 2.5 to 6.0 months before the time of ovulation until spawning. Mean fecundity was higher for females held at 7.2°C. Mean egg eye-up, hatch, and swim-up rates were also higher for females held at 7.2°C. Eggs collected 1, 4, and 7 d postovulation exhibited similar survival rates within females regardless of holding temperature.
Analysis of a Stock–Recruit Relationship for Red King Crab off Kodiak Island, Alaska
Authors: Bechtol William R. , Kruse Gordon H.
Published: May 2009

Waters of the northern Gulf of Alaska around Kodiak Island once supported the world's largest fishery for the red king crab Paralithodes camtschaticus. Commercial fisheries began at low levels in the 1930s, increasing rapidly in the 1960s to a peak harvest of 42,800 metric tons in 1965. Stock abundance declined sharply in the late 1960s, moderated in the 1970s, and crashed in the early 1980s. A commercial fishery closure since 1983 has not resulted in stock recovery. To improve understanding of stock dynamics, we examined spawner–recruit (S-R) relationships for the Kodiak red king crab stock. The shape of the S-R relationship helps describe average stock productivity at different stock levels, thus relating directly to fishery management objectives. Due to limited female data, we used only male data and two currencies of male abundance as a proxy for spawners: either (1) all males greater than or equal to 125 mm carapace length (CL) or (2) legal males (≥145 mm CL). Due to age uncertainty, we considered lag times of 5 to 8 years between reproduction and recruitment. Residuals from fitting a standard Ricker model were strongly negative for brood years from the mid-1970s to the mid-1980s and positive from the early to mid-1990s. A Ricker model with autocorrelated errors resulted in better fits with corrected Akaike's information criterion (AICc) values minimized for a 5-year lag using all males. Among model configurations, estimates of peak production ranged from 2.0 to 3.4 million recruits from a range of 11.3 to 37.7 million males. A model separating the time series into three productivity periods corresponding to different ecological regimes further improved model fit. Although abundances of both spawners and recruits have been less than 1.0 million males since 1985, depensation at low stock sizes was not detected. Future analyses will examine the contribution of ecological and environmental factors to crab recruitment.
Maturation and Reproduction of Shovelnose Sturgeon in the Middle Mississippi River
Authors: Tripp Sara J. , Phelps Quinton E. , Colombo Robert E. , Garvey James E. , Burr Brooks M. , Herzog David P. , Hrabik Robert A.
Published: May 2009

Shovelnose sturgeon Scaphirhynchus platorynchus in the middle Mississippi River provide one of the last commercially viable sturgeon fisheries in the world, yet their maturation and reproduction have not been linked. During 2005 and 2006, we sampled adult and age-0 shovelnose sturgeon to link age at maturation, the timing and periodicity of spawning, age-0 sturgeon production, and the resulting age-0 growth rates. Age at maturity was later than previous estimates, the minimum age of first maturation being 8 years for males and 9 years for females. Total egg count was slightly lower than previously reported (mean = 29,573 per female; SE = 2,472). Males and females typically spawned every 2 and 3 years, respectively. Peaks in mature fish coincided with rising river stages and water temperatures at which shovelnose sturgeon probably spawn. Peaks in spent adults followed. Age-0 shovelnose sturgeon occurred during June and July 2005 and May and June 2006, confirming successful spawning. Age-0 sturgeon grew between 0.69 and 1.69 mm total length/d; four distinct weekly cohorts occurred each year. During fall 2006, females contained ripe eggs, males were milting, and a single age-0 sturgeon (total length = 55 mm) was captured, suggesting that shovelnose sturgeon spawn during fall as well as spring. Management must consider the protracted nature of spawning within seasons as well as differences in spawning activity between seasons.