bluuebunny/crossref_metadata_2025 huggingface dataset:
Schizophrenia: Women Bear a Disproportionate Toll of Antipsychotic Side Effects
Authors: Seeman Mary V.
Published: January 2010

BACKGROUND: Men and women with schizophrenia suffer not only from their illness but also from the side effects of their medications. OBJECTIVE: To review the toll of antipsychotic side effects specifically on women. STUDY DESIGN: A review of the literature in the PubMed database since 1990 using search terms: sex difference, antipsychotics, schizophrenia, pharmacokinetics, pharmacodynamics, and pharmacogenomics and retrieving additional publications from the reference lists of the original articles. RESULTS: Findings suggest that, because of differing pharmacokinetics, women are more vulnerable than men to weight gain secondary to antipsychotics and to the consequences (metabolic, cardiovascular, reproductive) of weight gain. They are also more vulnerable to hyperprolactinemia and QTc prolongation. CONCLUSIONS: Dosing guidelines need to be critically appraised. The greater toll of side effects in women may undermine adherence to prescribed treatments, add to the stigma that attaches to mental illness, and diminish the quality of women’s lives. Side effects increase the cost of mental illness and heighten the burden experienced by caregivers. They exacerbate morbidity and raise mortality rates. They affect the children of women treated with antipsychotic medication.
The Art of Balancing
Authors: Kester Bernadette
Published: January 2010

/ This article examines the problems foreign correspondents encounter when working under conditions that differ considerably from those in their home country. In order to illustrate some of the problems, in particular with regard to the accessibility and trustworthiness of sources, the article takes as a case study the experiences of 11 Dutch correspondents posted in Moscow between 1982 and 2007, and examines their strategies to cope with the restrictions encountered working in a (neo-)authoritarian state.
Typology of Feeding Disorders Based on a Single Assessment System
Authors: Dovey Terence M. , Isherwood Elaine , Aldridge Victoria K. , Martin Clarissa I.
Published: January 2010

The highly individual and complex nature of feeding disorders makes the initial diagnosis and subsequent choice of which management strategy (MS) to employ professionally challenging. This article describes a clinical decision-making model employed and successfully implemented in England. Based on previous case study descriptions and quantitative data, the model offered here also suggests that there may be potential for subtypes of feeding disorders beyond the generic attribution of “feeding disordered” or “not feeding disordered.” To exemplify the current model, a brief description and prevalence breakdown of the types of feeding problems encountered within the authors’ clinical setting was also outlined. Following from these potential subtypes, specific and focused MS were delineated to offer guidance to professionals faced with developing and implementing feeding-based interventions.
Cellular barcoding tool for clonal analysis in the hematopoietic system
Authors: Gerrits Alice , Dykstra Brad , Kalmykowa Olga J. , Klauke Karin , Verovskaya Evgenia , Broekhuis Mathilde J. C. , de Haan Gerald , Bystrykh Leonid V.
Published: January 2010

Clonal analysis is important for many areas of hematopoietic stem cell research, including in vitro cell expansion, gene therapy, and cancer progression and treatment. A common approach to measure clonality of retrovirally transduced cells is to perform integration site analysis using Southern blotting or polymerase chain reaction–based methods. Although these methods are useful in principle, they generally provide a low-resolution, biased, and incomplete assessment of clonality. To overcome those limitations, we labeled retroviral vectors with random sequence tags or “barcodes.” On integration, each vector introduces a unique, identifiable, and heritable mark into the host cell genome, allowing the clonal progeny of each cell to be tracked over time. By coupling the barcoding method to a sequencing-based detection system, we could identify major and minor clones in 2 distinct cell culture systems in vitro and in a long-term transplantation setting. In addition, we demonstrate how clonal analysis can be complemented with transgene expression and integration site analysis. This cellular barcoding tool permits a simple, sensitive assessment of clonality and holds great promise for future gene therapy protocols in humans, and any other applications when clonal tracking is important.
PfPI3K, a phosphatidylinositol-3 kinase from Plasmodium falciparum, is exported to the host erythrocyte and is involved in hemoglobin trafficking
Authors: Vaid Ankush , Ranjan Ravikant , Smythe Wynand A. , Hoppe Heinrich C. , Sharma Pushkar
Published: January 2010

Polyphosphorylated phosphoinositides (PIPs) are potent second messengers, which trigger a wide variety of signaling and trafficking events in most eukaryotic cells. However, the role and metabolism of PIPs in malaria parasite Plasmodium have remained largely unexplored. Our present studies suggest that PfPI3K, a novel phosphatidylinositol-3-kinase (PI3K) in Plasmodium falciparum, is exported to the host erythrocyte by the parasite in an active form. PfPI3K is a versatile enzyme as it can generate various 3′-phosphorylated PIPs. In the parasite, PfPI3K was localized in vesicular compartments near the membrane and in its food vacuole. PI3K inhibitors wortmannin and LY294002 were effective against PfPI3K and were used to study PfPI3K function. We found that PfPI3K is involved in endocytosis from the host and trafficking of hemoglobin in the parasite. The inhibition of PfPI3K resulted in entrapment of hemoglobin in vesicles in the parasite cytoplasm, which prevented its transport to the food vacuole, the site of hemoglobin catabolism. As a result, hemoglobin digestion, which is a source of amino acids necessary for parasite growth, was attenuated and caused the inhibition of parasite growth.
HTLV-I Tax-dependent and -independent events associated with immortalization of human primary T lymphocytes
Authors: Bellon Marcia , Baydoun Hicham H. , Yao Yuan , Nicot Christophe
Published: January 2010

Human T-cell leukemia virus type I (HTLV-I)–associated malignancies are seen in a small percentage of infected persons. Although in vitro immortalization by HTLV-I virus is very efficient, we report that Tax has poor oncogenic activity in human primary T cells and that immortalization by Tax is rare. Sustained telomerase activity represents one of the oncogenic steps required for Tax-mediated immortalization. Tax expression was required for the growth of primary T cells, but was not sufficient to propel T cells into cell cycle in the absence of exogenous interleukin-2 (IL-2). Tax was sufficient to activate the phosphoinositide-3 kinase (PI3K)/Akt pathway as shown by down regulation of Src homology phosphatase-1 and increased phosphorylation of Akt. We also found disruption of putative tumor suppressors IL-16 and translocated promoter region (TPR) in Tax-immortalized and HTLV-I–transformed cell lines. Our results confirmed previous observations that Tax activates the anaphase-promoting complex. However, Tax did not affect the mitotic spindle checkpoint, which was also functional in HTLV-I–transformed cells. These data provide a better understanding of Tax functions in human T cells, and highlight the limitations of Tax, suggesting that other viral proteins are key to T-cell transformation and development of adult T-cell leukemia.
Interactions between flagellar and type III secretion proteins in Chlamydia pneumoniae
Authors: Stone Chris B , Bulir David C , Gilchrist Jodi D , Toor Raman K , Mahony James B
Published: January 2010

Background

Flagellar secretion systems are utilized by a wide variety of bacteria to construct the flagellum, a conserved apparatus that allows for migration towards non-hostile, nutrient rich environments. Chlamydia pneumoniae is an obligate, intracellular pathogen whose genome contains at least three orthologs of flagellar proteins, namely FliI, FlhA and FliF, but the role of these proteins remains unknown.

Results

Full length FliI, and fragments of FlhA, FliF, and FliI, were cloned and expressed as either GST or His tagged proteins in E. coli. The GST-tagged full length FliI protein was shown to possess ATPase activity, hydrolyzing ATP at a rate of 0.15 ± .02 μmol min-1 mg-1 in a time- and dose-dependant manner. Using bacterial-2-hybrid and GST pull-down assays, the N-terminal domain of FliI was shown to interact with the cytoplasmic domain of FlhA, but not with FliF, and the cytoplasmic domain of FlhA was shown to interact with the C-terminus of FliF. The absence of other flagellar orthologs led us to explore cross-reaction of flagellar proteins with type III secretion proteins, and we found that FliI interacted with CdsL and CopN, while FlhA interacted with CdsL and Cpn0322 (YscU ortholog CdsU).

Conclusions

The specific interaction of the four orthologous flagellar proteins in C. pneumoniae suggests that they interact in vivo and, taken together with their conservation across members of the chlamydiae sps., and their interaction with T3S components, suggests a role in bacterial replication and/or intracellular survival.
Tracing the origins of rescued chimpanzees reveals widespread chimpanzee hunting in Cameroon
Authors: Ghobrial Lora , Lankester Felix , Kiyang John A , Akih Akih E , de Vries Simone , Fotso Roger , Gadsby Elizabeth L , Jenkins Peter D , Gonder Mary K
Published: January 2010

Background

While wild chimpanzees are experiencing drastic population declines, their numbers at African rescue and rehabilitation projects are growing rapidly. Chimpanzees follow complex routes to these refuges; and their geographic origins are often unclear. Identifying areas where hunting occurs can help law enforcement authorities focus scarce resources for wildlife protection planning. Efficiently focusing these resources is particularly important in Cameroon because this country is a key transportation waypoint for international wildlife crime syndicates. Furthermore, Cameroon is home to two chimpanzee subspecies, which makes ascertaining the origins of these chimpanzees important for reintroduction planning and for scientific investigations involving these chimpanzees.

Results

We estimated geographic origins of 46 chimpanzees from the Limbe Wildlife Centre (LWC) in Cameroon. Using Bayesian approximation methods, we determined their origins using mtDNA sequences and microsatellite (STRP) genotypes compared to a spatial map of georeferenced chimpanzee samples from 10 locations spanning Cameroon and Nigeria. The LWC chimpanzees come from multiple regions of Cameroon or forested areas straddling the Cameroon-Nigeria border. The LWC chimpanzees were partitioned further as originating from one of three biogeographically important zones occurring in Cameroon, but we were unable to refine these origin estimates to more specific areas within these three zones.

Conclusions

Our findings suggest that chimpanzee hunting is widespread across Cameroon. Live animal smuggling appears to occur locally within Cameroon, despite the existence of local wildlife cartels that operate internationally. This pattern varies from the illegal wildlife trade patterns observed in other commercially valuable species, such as elephants, where specific populations are targeted for exploitation. A broader sample of rescued chimpanzees compared against a more comprehensive grid of georeferenced samples may reveal 'hotspots' of chimpanzee hunting and live animal transport routes in Cameroon. These results illustrate also that clarifying the origins of refuge chimpanzees is an important tool for designing reintroduction programs. Finally, chimpanzees at refuges are frequently used in scientific investigations, such as studies investigating the history of zoonotic diseases. Our results provide important new information for interpreting these studies within a precise geographical framework.
Naturally-acquired humoral immune responses against the N- and C-termini of the Plasmodium vivax MSP1 protein in endemic regions of Brazil and Papua New Guinea using a multiplex assay
Authors: Fernandez-Becerra Carmen , Sanz Sergi , Brucet Marina , Stanisic Danielle I , Alves Fabiana P , Camargo Erney P , Alonso Pedro L , Mueller Ivo , del Portillo Hernando A
Published: January 2010

Background

Progress towards the development of a malaria vaccine againstPlasmodium vivax, the most widely distributed human malaria parasite, will require a better understanding of the immune responses that confer clinical protection to patients in regions where malaria is endemic.

Methods

GlutathioneS-transferase (GST) and GST-fusion proteins representing the N- terminus of the merozoite surface protein 1 ofP. vivax, PvMSP1-N, and the C-terminus, PvMSP1-C, were covalently coupled to BioPlex carboxylated beads. Recombinant proteins and coupled beads were used, respectively, in ELISA and Bioplex assays using immune sera ofP. vivaxpatients from Brazil and PNG to determine IgG and subclass responses. Concordances between the two methods in the seropositivity responses were evaluated using the Kappa statistic and the Spearman's rank correlation.

Results

The results using this methodology were compared with the classical microtitre enzyme-linked immnosorbent assay (ELISA), showing that the assay was sensitive, reproducible and had good concordance with ELISA; yet, further research into different statistical analyses seems desirable before claiming conclusive results exclusively based on multiplex assays. As expected, results demonstrated that PvMSP1 was immunogenic in natural infections of patients from different endemic regions of Brazil and Papua New Guinea (PNG), and that age correlated only with antibodies against the C-terminus part of the molecule. Furthermore, the IgG subclass profiles were different in these endemic regions having IgG3 predominantly recognizing PvMSP1 in Brazil and IgG1 predominantly recognizing PvMSP1 in PNG.

Conclusions

This study validates the use of the multiplex assay to measure naturally-acquired IgG antibodies against the merozoite surface protein 1 ofP. vivax.
The total antioxidant content of more than 3100 foods, beverages, spices, herbs and supplements used worldwide
Authors: Carlsen Monica H , Halvorsen Bente L , Holte Kari , Bøhn Siv K , Dragland Steinar , Sampson Laura , Willey Carol , Senoo Haruki , Umezono Yuko , Sanada Chiho , Barikmo Ingrid , Berhe Nega , Willett Walter C , Phillips Katherine M , Jacobs David R , Blomhoff Rune
Published: January 2010

Background

A plant-based diet protects against chronic oxidative stress-related diseases. Dietary plants contain variable chemical families and amounts of antioxidants. It has been hypothesized that plant antioxidants may contribute to the beneficial health effects of dietary plants. Our objective was to develop a comprehensive food database consisting of the total antioxidant content of typical foods as well as other dietary items such as traditional medicine plants, herbs and spices and dietary supplements. This database is intended for use in a wide range of nutritional research, from in vitro and cell and animal studies, to clinical trials and nutritional epidemiological studies.

Methods

We procured samples from countries worldwide and assayed the samples for their total antioxidant content using a modified version of the FRAP assay. Results and sample information (such as country of origin, product and/or brand name) were registered for each individual food sample and constitute the Antioxidant Food Table.

Results

The results demonstrate that there are several thousand-fold differences in antioxidant content of foods. Spices, herbs and supplements include the most antioxidant rich products in our study, some exceptionally high. Berries, fruits, nuts, chocolate, vegetables and products thereof constitute common foods and beverages with high antioxidant values.

Conclusions

This database is to our best knowledge the most comprehensive Antioxidant Food Database published and it shows that plant-based foods introduce significantly more antioxidants into human diet than non-plant foods. Because of the large variations observed between otherwise comparable food samples the study emphasizes the importance of using a comprehensive database combined with a detailed system for food registration in clinical and epidemiological studies. The present antioxidant database is therefore an essential research tool to further elucidate the potential health effects of phytochemical antioxidants in diet.
Molecular characterization of two hantavirus strains from different rattus species in Singapore
Authors: Johansson Patrik , Yap Grace , Low Hwee-Teng , Siew Chern-Chiang , Kek Relus , Ng Lee-Ching , Bucht Göran
Published: January 2010

Background

Hantaviruses cause human disease in endemic regions around the world. Outbreaks of hantaviral diseases have been associated with changes in rodent population density and adaptation to human settlements leading to their proliferation in close proximity to human dwellings. In a parallel study initiated to determine the prevalence of pathogens in Singapore's wild rodent population, 1206 rodents were trapped and screened. The findings established a hantavirus seroprevalence of 34%. This paper describes the molecular characterization of hantaviruses from Rattus norvegicus and Rattus tanezumi, the predominant rodents caught in urban Singapore.

Methodology

Pan-hanta RT-PCR performed on samples of Rattus norvegicus and Rattus tanezumi indicated that 27 (2.24%) of the animals were positive. sequence analysis of the S and M segments established that two different hantavirus strains circulate in the rodent population of Singapore. Notably, the hantavirus strains found in Rattus norvegicus clusters with other Asian Seoul virus sequences, while the virus strains found in Rattus tanezumi had the highest sequence similarity to the Serang virus from Rattus tanezumi in Indonesia, followed by Cambodian hantavirus isolates and the Thailand virus isolated from Bandicota indica.

Conclusions

Sequence analysis of the S and M segments of hantavirus strains found in Rattus norvegicus (Seoul virus strain Singapore) and Rattus tanezumi (Serang virus strain Jurong TJK/06) revealed that two genetically different hantavirus strains were found in rodents of Singapore. Evidently, together with Serang, Cambodian and Thailand virus the Jurong virus forms a distinct phylogroup. Interestingly, these highly similar virus strains have been identified in different rodent hosts. Further studies are underway to analyze the public health significance of finding hantavirus strains in Singapore rodents.
Vitamin A depletion alters sensitivity of motor behavior to MK-801 in C57BL/6J mice
Authors: Zhang Ming , Ji Baohu , Zou Hong , Shi Junwei , Zhang Zhao , Li Xingwang , Zhu Hui , Feng Guoyin , Jin Meilei , Yu Lei , He Lin , Wan Chunling
Published: January 2010

Background

Vitamin A and its derivatives (retinoids) are crucial for the development, maintenance and morphogenesis of the central nervous system (CNS). Although motor impairment has been reported in postnatal vitamin A depletion rodents, the effect of vitamin A depletion on homeostasis maintaining capability in response to external interference is not clear.

Methods

In the current study, we measured the effect of vitamin A depletion on motor ability and pain sensitivity under two different conditions: 1. prior to any injection and 2. after the injection of an N-methyl-D-aspartate (NMDA) receptor antagonist (MK-801).

Results

Vitamin A depletion mice showed decreased body weight, enhanced locomotor activity, increased rearing and less tail flick latency. Vitamin A depletion also induced hypersensitivity of stereotypy, ataxia, rearing, and tail flick latency to MK-801, but hyposensitivity of locomotion to MK-801.

Conclusions

These findings suggest that vitamin A depletion affect broad basal behavior and disrupt homeostasis maintaining capability in response to glutamate perturbation. We provide a useful animal model for assessing the role of vitamin A depletion in regulating animal behavior, and for detecting how neurotransmitter pathways might be involved in vitamin A depletion related behavioral abnormalities.
Brn3a regulates neuronal subtype specification in the trigeminal ganglion by promoting Runx expression during sensory differentiation
Authors: Dykes Iain M , Lanier Jason , Raisa Eng S , Turner Eric E
Published: January 2010

The transcription factor Brn3a, product of the pou4f1 gene, is expressed in most sensory neurons throughout embryogenesis. Prior work has demonstrated a role for Brn3a in the repression of early neurogenic genes; here we describe a second major role for Brn3a in the specification of sensory subtypes in the trigeminal ganglion (TG). Sensory neurons initially co-express multiple Trk-family neurotrophin receptors, but are later marked by the unique expression of TrkA, TrkB or TrkC. Maturation of these sensory subtypes is known to depend on the expression of Runx transcription factors. Newborn Brn3a knockout mice fail to express TrkC, which is associated in the TG with mechanoreceptors, plus a set of functional genes associated with nociceptor subtypes. In embryonic Brn3a-/- ganglia, the normal expression of Runx3 is never initiated in TrkC+ neurons, and Runx1 expression is greatly attenuated in TrkA+ nociceptors. These changes are accompanied by expanded expression of TrkB in neurons that abnormally express multiple Trks, followed by the loss of TrkC and TrkA expression. In transgenic embryos expressing a Brn3a-VP16 dominant transactivator, Runx3 mRNA expression is increased, suggesting that it is a direct regulatory target of Brn3a. Chromatin immunoprecipitation confirms that Brn3a binds in vivo to a conserved upstream enhancer element within histone H3-acetylated chromatin in the Runx3 locus. Together these data show that Brn3a acts upstream of the Runx factors, which then repress TrkB expression to allow establishment of the non-overlapping Trk receptor profiles and correct terminally differentiated phenotypes.
Mast cell tumours and other skin neoplasia in Danish dogs - data from the Danish Veterinary Cancer Registry
Authors: Brønden Louise B , Eriksen Thomas , Kristensen Annemarie T
Published: January 2010

Background

The Danish Veterinary Cancer Registry (DVCR) was established in May 2005 to gather information about neoplasms in the Danish dog and cat populations. Practitioners from more than 60 clinics throughout Denmark have submitted data on these species. The objectives of the current study were, with a special focus on mast cell tumours (MCT) to investigate the occurrence, gender distribution, biological behaviour, locations, types, the diagnostic method used and treatment of skin neoplasms in dogs based on information reported to the DVCR.

Methods

From May 15th 2005 through February 29th 2008, reports on a total of 1,768 canine cases of neoplasia in the skin, subcutis or adnexa were submitted.) Of these, 765 cases (43%) were confirmed by cytology or histopathology.

Results

The majority of dogs had a benign neoplasm (66%) while 21% were cases of malignant neoplasia. The most commonly encountered malignant neoplasms were MCT and soft tissue sarcomas and for benign neoplasms, lipomas and histiocytomas were the most common. The location of the neoplasms were primarily in the cutis, subcutis or in the perianal region. The occurrence, gender distribution, biological behaviour and location of canine skin neoplasias in Denmark were similar to earlier reports, although some national variations occurred. A correlation between grade of MCT and the proportion of cases treated surgically was observed.

Conclusions

Population based cancer registries like the DVCR are of importance in the collection of non-selected primary information about occurrence and distribution of neoplasms. The DVCR provides detailed information on cases of skin neoplasms in dogs and may serve as a platform for the study of sub-sets of neoplastic diseases (e.g. MCT) or subgroups of the canine population (e.g. a specific breed).
Unilateral optic neuropathy following subdural hematoma: a case report
Authors: Kretz Alexandra , Preul Christoph , Fricke Hans-Joerg , Witte Otto W , Terborg Christoph
Published: January 2010

Introduction

Unilateral optic neuropathy is commonly due to a prechiasmatic affliction of the anterior visual pathway, while losses in visual hemifields result from the damage to brain hemispheres. Here we report the unusual case of a patient who suffered from acute optic neuropathy following hemispherical subdural hematoma. Although confirmed up to now only through necropsy studies, our case strongly suggests a local, microcirculatory deficit identified through magnetic resonance imaging in vivo.

Case presentation

A 70-year-old Caucasian German who developed a massive left hemispheric subdural hematoma under oral anticoagulation presented with acute, severe visual impairment on his left eye, which was noticed after surgical decompression. Neurologic and ophthalmologic examinations indicated sinistral optic neuropathy with visual acuity reduced nearly to amaurosis. Ocular pathology such as vitreous body hemorrhage, papilledema, and central retinal artery occlusion were excluded. An orbital lesion was ruled out by means of orbital magnetic resonance imaging. However, cerebral diffusion-weighted imaging and T2 maps of magnetic resonance imaging revealed a circumscribed ischemic lesion within the edematous, slightly herniated temporomesial lobe within the immediate vicinity of the affected optic nerve. Thus, the clinical course and morphologic magnetic resonance imaging findings suggest the occurrence of pressure-induced posterior ischemic optic neuropathy due to microcirculatory compromise.

Conclusion

Although lesions of the second cranial nerve following subdural hematoma have been reported individually, their pathogenesis was preferentially proposed from autopsy studies. Here we discuss a dual, pressure-induced and secondarily ischemic pathomechanism on the base of in vivo magnetic resonance imaging diagnostics which may remain unconsidered by computed tomography.
Towards the integration of mouse databases - definition and implementation of solutions to two use-cases in mouse functional genomics
Authors: Gruenberger Michael , Alberts Rudi , Smedley Damian , Swertz Morris , Schofield Paul ,   The CASIMIR consortium, Schughart Klaus
Published: January 2010

Background

The integration of information present in many disparate biological databases represents a major challenge in biomedical research. To define the problems and needs, and to explore strategies for database integration in mouse functional genomics, we consulted the biologist user community and implemented solutions to two user-defined use-cases.

Results

We organised workshops, meetings and used a questionnaire to identify the needs of biologist database users in mouse functional genomics. As a result, two use-cases were developed that can be used to drive future designs or extensions of mouse databases. Here, we present the use-cases and describe some initial computational solutions for them. The application for the gene-centric use-case, "MUSIG-Gen" starts from a list of gene names and collects a wide range of data types from several distributed databases in a "shopping cart"-like manner. The iterative user-driven approach is a response to strongly articulated requests from users, especially those without computational biology backgrounds. The application for the phenotype-centric use-case, "MUSIG-Phen", is based on a similar concept and starting from phenotype descriptions retrieves information for associated genes.

Conclusion

The use-cases created, and their prototype software implementations should help to better define biologists' needs for database integration and may serve as a starting point for future bioinformatics solutions aimed at end-user biologists.
Differential expression of decorin, EGFR and cyclin D1 during mammary gland carcinogenesis in TA2 mice with spontaneous breast cancer
Authors: Gu Yanjun , Zhang Shiwu , Wu Qiang , Xu Shaoyan , Cui Yanfen , Yang Zhengduo , Zhao Xiulan , Sun Baocun
Published: January 2010

Background

The Tientsin Albino 2 (TA2) mouse is an inbred strain originating from the Kunming strain. It has a high incidence of spontaneous breast cancer without the need for external inducers or carcinogens. Until now, the mechanism of carcinogenesis has remained unclear. In this study, we investigate differential gene expression, especially the expression of decorin, EGFR and cyclin D1, during mammary gland epithelial cell carcinogenesis in TA2 mice.

Methods

Gene expression profiles of spontaneous breast cancer and matched normal mammary gland tissues in TA2 mice were ascertained using an Affymetrix Mouse 430 2.0 array. Twelve mammary tissue samples from five month-old female TA2 mice (Group A), as well as 28 samples from mammary (Group B) and cancer tissues (Group C) of spontaneous breast cancer-bearing TA2 mice, were subsequently used to detect the expression of decorin, EGFR and cyclin D1 by real-time PCR and immunohistochemical methods.

Results

Several imprinted genes, oncogenes and tumor suppressor genes were differentially expressed between normal mammary gland tissues and breast cancer tissues of TA2 mice. The imprinted gene decorin and the oncogene EGFR were down-regulated in tumor tissues, while the oncogene cyclin D1 was up-regulated. Immunohistochemistry showed that samples in Group A showed high decorin expression more frequently than those in Group B (P< 0.05). More tissue samples in Group B than Group A were positive for nuclear EGFR, and tissue samples in Group B more frequently showed high nuclear EGFR expression than those in Group A or Group C (P< 0.05). The labeling index for cyclin D1 in Group C was significantly higher than in Group B. Mammary tissues of Group A expressed the highest level of decorin mRNA (P< 0.05), and mammary tissues of Group B expressed the highest level of EGFR mRNA (P< 0.05), while cancer tissues expressed the highest level of cyclin D1 mRNA (P< 0.05).

Conclusions

The expression of decorin, EGFR and cyclin D1 in mammary epithelial cells changes with increasing age. The abnormal expression of them may partly contribute to the genesis of spontaneous breast cancer in TA2 mice.
Regulation of IFN response gene activity during infliximab treatment in rheumatoid arthritis is associated with clinical response to treatment
Authors: van Baarsen Lisa GM , Wijbrandts Carla A , Rustenburg François , Cantaert Tineke , van der Pouw Kraan Tineke CTM , Baeten Dominique L , Dijkmans Ben AC , Tak Paul P , Verweij Cornelis L
Published: January 2010

Introduction

Cross-regulation between TNF and type I IFN has been postulated to play an important role in autoimmune diseases. Therefore, we determined the effect of TNF blockade in rheumatoid arthritis (RA) on the type I IFN response gene activity in relation to clinical response.

Methods

Peripheral blood from 33 RA patients was collected in PAXgene tubes before and after the start of infliximab treatment. In a first group of 15 patients the baseline expression of type I IFN-regulated genes was determined using cDNA microarrays and compared to levels one month after treatment. The remaining 18 patients were studied as an independent group for validation using quantitative polymerase chain reaction (qPCR).

Results

Gene expression analysis revealed that anti-TNF antibody treatment induced a significant increase in type I IFN response gene activity in a subset of RA patients, whereas expression levels remained similar or were slightly decreased in others. The findings appear clinically relevant since patients with an increased IFN response gene activity after anti-TNF therapy had a poor clinical outcome. This association was confirmed and extended for an IFN response gene set consisting of OAS1, LGALS3BP, Mx2, OAS2 and SERPING1 in five EULAR good and five EULAR poor responders, by qPCR.

Conclusions

Regulation of IFN response gene activity upon TNF blockade in RA is not as consistent as previously described, but varies between patients. The differential changes in IFN response gene activity appear relevant to the clinical outcome of TNF blockade in RA.
Genome-wide prediction of transcription factor binding sites using an integrated model
Authors: Won Kyoung-Jae , Ren Bing , Wang Wei
Published: January 2010

We present an integrated method called Chromia for the genome-wide identification of functional target loci of transcription factors. Designed to capture the characteristic patterns of transcription factor binding motif occurrences and the histone profiles associated with regulatory elements such as promoters and enhancers, Chromia significantly outperforms other methods in the identification of 13 transcription factor binding sites in mouse embryonic stem cells, evaluated by both binding (ChIP-seq) and functional (RNA interference knockdown) experiments.
Glucocorticoid Receptor Activates Poised FKBP51 Locus through Long-Distance Interactions
Authors: Paakinaho Ville , Makkonen Harri , Jääskeläinen Tiina , Palvimo Jorma J.
Published: January 2010

Recent studies have identified FKBP51 (FK506-binding protein 51) as a sensitive biomarker of corticosteroid responsiveness in vivo. In this work, we have elucidated the molecular mechanisms underlying the induction of FKBP51 by the glucocorticoid receptor (GR) in human A549 lung cancer cells showing robust accumulation of FKBP51 mRNA in response to dexamethasone exposure. Our quantitative chromatin immunoprecipitation scans and enhancer activity analyses indicate that activation of the FKBP51 locus by glucocorticoids in vivo is triggered by the loading of GR to enhancers at about 34 kb 5′ and about 87 kb 3′ of the transcription start site. Interestingly, the region encompassing these enhancers is bordered by CCCTC-binding factor- and cohesin-binding sites. Dexamethasone treatment also decreased the histone density at several regions of the gene, which was paralleled with the occupancy of SWI/SNF chromatin remodeling complexes within the locus. Moreover, silencing of BRM subunit of the SWI/SNF complex blunted the glucocorticoid induction of the locus. The proximal promoter region along with the major intronic enhancer at approximately 87 kb, at which the GR binding peaked, had elevated levels of histone 3 acetylation and H3K4 trimethylation, whereas H3K36 trimethylation more generally marked the gene body and reflected the occupancy of RNA polymerase II. The occurrence of these active chromatin marks within the FKBP51 locus before glucocorticoid exposure suggests that it is poised for transcription in A549 cells. Taken together, these results indicate that the holo-GR is capable of activating transcription and evoking changes in chromatin structure through distant-acting enhancers.
Transactivation of the Epidermal Growth Factor Receptor Is Involved in the Lutropin Receptor-Mediated Down-Regulation of Ovarian Aromatase Expression in Vivo
Authors: Andric Nebojsa , Thomas Mika , Ascoli Mario
Published: January 2010

Ovarian follicular development and differentiation is characterized by dramatic changes in aromatase (Cyp19a1) expression. In preovulatory follicles, activation of the FSH receptor increases aromatase expression until the surge of LH decreases it. Here we provide in vivo evidence that down-regulation of Cyp19a1 by the LH surge requires efficient signaling through the epidermal growth factor receptor (EGFR). The human chorionic gonadotropin (hCG)-induced down-regulation of Cyp19a1 expression in the two different mouse models with inactivating mutations of the EGFR (wa2 and velvet) is impaired but not abolished. The hCG-induced phosphorylation of ovarian ERK1/2, expression of C/EBPβ, and the phosphorylation of Connexin43 (two downstream targets of ERK1/2 action) are also decreased in these two mouse models. In contrast, disruption of EGFR signaling does not have any affect on the hCG-induced phosphorylation of cAMP response element-binding protein or AKT. This study provides the first in vivo evidence linking the LH receptor, the EGFR, and ERK1/2 as sequential components of a pathway that regulates ovarian Cyp19a1 expression.
Book Reviews
Authors: Freeman David S.
Published: January 2010

Spiritual resources in family therapy (2nd edition)
Book Reviews
Authors: Germer Christopher K.
Published: January 2010

The compassionate mind: A new approach to life's challenges
Book Reviews
Authors: Morrison Todd
Published: January 2010

The nature of sexual desire
Book Reviews
Authors: Fulton Paul R.
Published: January 2010

Ten Zen questions
Explanatory dictionary of key terms in toxicology: Part II (IUPAC Recommendations 2010)
Authors: Nordberg Monica , Duffus John H. , Templeton Douglas M.
Published: January 2010

The objective of the “Explanatory Dictionary of Key Terms in Toxicology” is to give full explanations of the meaning and usage of toxicological terms chosen for their importance and complexity with regard to the merging of chemistry into toxicology. This requires a full description of the underlying concepts, going beyond a normal dictionary definition. Often linguistic barriers lead to problems in obtaining a common understanding of terminology at an international level and between disciplines. The explanatory comments should help to break down such barriers. This dictionary is a follow-up and continuation of part I published in 2007. It consists of a collection of terms chosen from the IUPAC “Glossary of Terms Used in Toxicology”. These terms are organized under 19 main headings. The authors hope that this explanatory dictionary will be helpful to chemists, pharmacologists, toxicologists, risk assessors, regulators, medical practitioners, regulatory authorities, and everyone with an interest in the application of chemistry to solving toxicological problems. It should be of particular value to those involved in risk assessment and management.
MicroRNA-21 Is Induced Early in Pancreatic Ductal Adenocarcinoma Precursor Lesions
Authors: du Rieu Maël Chalret , Torrisani Jérôme , Selves Janick , Al Saati Talal , Souque Anny , Dufresne Marlène , Tsongalis Gregory J , Suriawinata Arief A , Carrère Nicolas , Buscail Louis , Cordelier Pierre
Published: January 2010

Background: Pancreatic ductal adenocarcinoma (PDAC) has the poorest overall prognosis among gastrointestinal cancers; however, curative resection in early-stage PDAC greatly improves survival rates, indicating the importance of early detection. Because abnormal microRNA production is commonly detected in cancer, we investigated noninvasive precursor pancreatic intraepithelial neoplasia (PanIN) lesions for microRNA production as a potential early biomarker of PDAC.

Methods: Pathologists identified and classified ductal lesions. We extracted total RNA from laser-capture microdissected PanIN tissue samples from a conditional KRAS(G12D) mouse model (n = 29) or of human origin (n = 38) (KRAS is v-Ki-ras2 Kirsten rat sarcoma viral oncogene homolog). MicroRNA production was quantified by quantitative real-time PCR. Internal controls included 5S and U6 RNAs.

Results: Production of microRNAs miR-21, miR-205, and miR-200 paralleled PanIN progression in the KRAS(G12D) mouse model, compared with microRNA production in samples of nonpathologic ducts. miR-21 demonstrated the highest relative concentrations in the precursor lesions. Interestingly, miR-205 and miR-21 up-regulation preceded phenotypic changes in the ducts. The production of microRNAs miR-21, miR-221, miR-222, and let-7a increased with human PanIN grade, with peak production occurring in hyperplastic PanIN-2/3 lesions. In situ hybridization analysis indicated miR-21 production to be concentrated in pathologic ductal cells. miR-21 production was regulated by KRAS(G12D) and epidermal growth factor receptor in PDAC-derived cell lines.

Conclusions: Aberrant microRNA production is an early event in the development of PanIN. Our findings indicate that miR-21 warrants further investigation as a marker for early detection of PDAC.
Magnox Steel Reactor Pressure Vessel Monitoring Schemes—An Overview
Authors: Wootton M. R. , Moskovic R. , Bolton C. J. , Flewitt P. E. J.
Published: January 2010

The steel pressure vessel Magnox reactors were designed in the 1950s and were made from C–Mn plate steel and forgings welded together using a mixture of submerged-arc and manual metal arc weld metals. Each reactor contained surveillance capsules with specimens of plate steel, forgings, and the different weld metals to monitor the effects of irradiation on the Charpy impact and tensile properties. Canisters were withdrawn over the operating life and measurements were taken. During the lifetime of the fleet, there were developments in testing, observed changes in properties, and understanding of the radiation damage process that challenged the safety cases to support the operation of the stations. At the time the reactors were designed, the concept of fracture toughness was only beginning to be investigated, yet during the lifetime of the stations, fracture toughness testing was successfully adopted as standard practice as an input to fracture mechanics based assessment of the steel vessels. Both hardening and non-hardening embrittlements, the latter due to impurity phosphorus segregation in weld metal, were successfully addressed. At a relatively late stage the contribution of “thermal neutrons” to embrittlement was identified as being significant and was successfully incorporated into the assessment process. This led to the adoption of sophisticated statistical techniques to assess changes in properties of the most critical construction material—submerged-arc weld metal. A large scale sampling and testing programme of submerged-arc weld metal from a decommissioned reactor validated the assessment process. As a result of successfully addressing these and other challenges when the last two steel pressure vessel stations closed in December 2006, they had achieved lifetimes of nearly 40 years.
Influence of Neutron Irradiation on Energy Accumulation and Dissipation during Plastic Flow and Hardening of Metallic Polycrystals
Authors: Toktogulova D. A. , Gusev M. N. , Maksimkin O. P. , Garner F. A.
Published: January 2010

Deformation-calorimetric experiments have been performed on specimens of Armco iron, pure nickel, and two austenitic chromium-nickel alloys: 12Cr18Ni10Ti and 03Cr20Ni45Mo4Nb, each tested in both unirradiated and irradiated conditions. It has been shown that for neutron-irradiated 12Cr18Ni10Ti stainless steel and also for nickel and Armco iron, the latent energy (Es) versus σ curves shift towards lower values of Es, and these curves progressively lose their parabolic appearance that is typical for unirradiated metals and alloys. It has also been shown experimentally that “excess heat” is measured when stored energy associated with radiation-produced defect agglomerates is released during their annihilation in formation of defect-free channels. In effect more energy in released than the mechanical energy supplied externally to cause deformation of the specimen. When post-irradiation annealing is used to reduce the concentration of defect agglomerates, the excess energy phenomenon disappears.
Lessons Learned from RAP Sections with 17 Years of Service
Authors: Chen Dar-Hao , Hong Feng
Published: January 2010

Maintenance and rehabilitation (M&R) play a key role in maintaining aging highway infrastructures. Asphalt concrete (AC) overlays have been widely used in M&R across the state. The successful application of an AC overlay requires comprehensive and in-depth knowledge regarding its material characteristics and in situ performance. To better understand the AC overlay’s behavior, the Texas SPS-5 sections from the Long-Term Pavement Performance program are investigated in this study. The eight test sections perform satisfactorily even after 17 years of service. The purpose of this study is to extract useful information and propagate this success to similar rehabilitation projects. The study includes two aspects of work complementary to each other: (A) Laboratory material properties testing (binder and aggregate tests, overlay tester test, and the Hamburg wheel track test) and (B) in situ pavement performance evaluation (transverse cracking, reflective cracking, rut depth, and ride quality). By integrating the information from both aspects, the findings are given as follows: (1) AC overlay with 35 % reclaimed asphalt pavement (RAP) can perform well if properly designed and constructed; (2) in terms of resisting reflective cracking 1 unit thick of 35 % RAP is equivalent to 0.26 unit thick virgin mixture; (3) with the 40 % reflective cracking rate criterion, the life for virgin AC with a 125 mm overlay is 65 % longer than that for a 50 mm overlay; (4) in terms of pavement performance, no significant difference exists between 50 mm milling and non-milling if the milling does not remove existing cracks completely; (5) the maximum rut depth of 12.7 mm among the test sections indicates that the mixture is rut-resistant, and the existing pavement with lime-treated base and subbase beneath the overlay provides sound foundation; and (6) the overlay tester can be a viable and simple measure to evaluate the asphalt mixtures’ reflective cracking resistance.
Water Vapor Sorption Isotherms for Southern Pine Treated with Several Waterborne Preservatives
Authors: Zelinka Samuel L. , Glass Samuel V.
Published: January 2010

Equilibrium moisture content (EMC) was measured over a range of relative humidities at 22.5°C to determine whether certain wood preservatives increase the hygroscopicity of southern pine (Pinus sp.) The treatments studied were alkaline copper quaternary (ACQ) at a retention of 6.6 kg⋅m−3, chromated copper arsenate (CCA) at 6.9 kg⋅m−3, and disodium octaborate tetrahydrate (DOT) at 3.8 kg⋅m−3 (equivalent to 2.6 kg⋅m−3 as B2O3). All treatments examined increased the EMC at relative humidities above 60 %. Wood treated with DOT was the most hygroscopic. At high relative humidities, the ratio of the EMC of ACQ-treated wood to CCA-treated wood was 1.08. It is unlikely that the higher corrosiveness of ACQ compared with CCA is due to this slight increase in hygroscopicity.
Beethoven's Other Humanism
Authors: Chua Daniel K. L.
Published: January 2010

Beethoven's Promethean image has been reenforced in recent scholarship by the idea of the “heroic.” Although the escalation of the concept has been recognized as an act of selective hearing based on a handful of “heroic” works, Beethoven's Promethean identity is likely to remain because it embodies the ethical values of a particularly virulent strain of humanism; Beethoven is still employed today to mark the epochal events of human history—from the fall of the Berlin Wall to the atrocities of 9/11. However, the humanism this hero champions has been accused as a cause of the very inhumanity the music is suppose to erase. To offer an alternative is not difficult—there are many works by the composer that do not conform to the Promethean image; but the alternative would be meaningless if it were merely a matter of registering other topics or narratives without grounding the difference in a set of values that challenge the ethical force of the hero. This article sketches the possibility of such an alternative through the ethics of philosophers such as Emmanuel Lévinas and Theodor W. Adorno. It explores an-Other humanism in Beethoven both in the sense of an other Beethoven and a humanism founded on the Other.