bluuebunny/crossref_metadata_2025 huggingface dataset:
BIAdb: A curated database of benzylisoquinoline alkaloids
Authors: Singla Deepak , Sharma Arun , Kaur Jasjit , Panwar Bharat , Raghava Gajendra PS
Published: March 2010

Background

Benzylisoquinoline is the structural backbone of many alkaloids with a wide variety of structures including papaverine, noscapine, codeine, morphine, apomorphine, berberine, protopine and tubocurarine. Many benzylisoquinoline alkaloids have been reported to show therapeutic properties and to act as novel medicines. Thus it is important to collect and compile benzylisoquinoline alkaloids in order to explore their usage in medicine.

Description

We extract information about benzylisoquinoline alkaloids from various sources like PubChem, KEGG, KNApSAcK and manual curation from literature. This information was processed and compiled in order to create a comprehensive database of benzylisoquinoline alkaloids, called BIAdb. The current version of BIAdb contains information about 846 unique benzylisoquinoline alkaloids, with multiple entries in term of source, function leads to total number of 2504 records. One of the major features of this database is that it provides data about 627 different plant species as a source of benzylisoquinoline and 114 different types of function performed by these compounds. A large number of online tools have been integrated, which facilitate user in exploring full potential of BIAdb. In order to provide additional information, we give external links to other resources/databases. One of the important features of this database is that it is tightly integrated with Drugpedia, which allows managing data in fixed/flexible format.

Conclusions

A database of benzylisoquinoline compounds has been created, which provides comprehensive information about benzylisoquinoline alkaloids. This database will be very useful for those who are working in the field of drug discovery based on natural products. This database will also serve researchers working in the field of synthetic biology, as developing medicinally important alkaloids using synthetic process are one of important challenges. This database is available from http://crdd.osdd.net/raghava/biadb/.
Accumulation of phenanthrene by roots of intact wheat (Triticum acstivnmL.) seedlings: passive or active uptake?
Authors: Zhan Xin-Hua , Ma Heng-Liang , Zhou Li-Xiang , Liang Jian-Ru , Jiang Ting-Hui , Xu Guo-Hua
Published: March 2010

Background

Polycyclic aromatic hydrocarbons (PAHs) are of particular concern due to their hydrophobic, recalcitrant, persistent, potentially carcinogenic, mutagenic and toxic properties, and their ubiquitous occurrence in the environment. Most of the PAHs in the environment are present in surface soil. Plants grown in PAH-contaminated soils or water can become contaminated with PAHs because of their uptake. Therefore, they may threaten human and animal health. However, the mechanism for PAHs uptake by crop roots is little understood. It is important to understand exactly how PAHs are transported into the plant root system and into the human food chain, since it is beneficial in governing crop contamination by PAHs, remedying soils or waters polluted by PAHs with plants, and modeling potential uptake for risk assessment.

Results

The possibility that plant roots may take up phenanthrene (PHE), a representative of PAHs, via active process was investigated using intact wheat (Triticum acstivnm L.) seedlings in a series of hydroponic experiments. The time course for PHE uptake into wheat roots grown in Hoagland solution containing 5.62 μM PHE for 36 h could be separated into two periods: a fast uptake process during the initial 2 h and a slow uptake component thereafter. Concentration-dependent PHE uptake was characterized by a smooth, saturable curve with an apparent K
m of 23.7 μM and a V
max of 208 nmol g-1 fresh weight h-1, suggesting a carrier-mediated uptake system. Competition between PHE and naphthalene for their uptake by the roots further supported the carrier-mediated uptake system. Low temperature and 2,4-dinitrophenol (DNP) could inhibit PHE uptake equally, indicating that metabolism plays a role in PHE uptake. The inhibitions by low temperature and DNP were strengthened with increasing concentration of PHE in external solution within PHE water solubility (7.3 μM). The contribution of active uptake to total absorption was almost 40% within PHE water solubility. PHE uptake by wheat roots caused an increase in external solution pH, implying that wheat roots take up PHE via a PHE/nH+ symport system.

Conclusion

It is concluded that an active, carrier-mediated and energy-consuming influx process is involved in the uptake of PHE by plant roots.
Uncoupled responses of Smad4-deficient cancer cells to TNFα result in secretion of monomeric laminin-γ2
Authors: Zboralski Dirk , Warscheid Bettina , Klein-Scory Susanne , Malas M. Bassel , Becker Heiko , Böckmann Miriam , Meyer Helmut E , Schmiegel Wolff , Simon-Assmann Patricia , Schwarte-Waldhoff Irmgard
Published: March 2010

Background

Functional loss of the tumor suppressor Smad4 is involved in pancreatic and colorectal carcinogenesis and has been associated with the acquisition of invasiveness. We have previously demonstrated that the heterotrimeric basement membrane protein laminin-332 is a Smad4 target. Namely, Smad4 functions as a positive transcriptional regulator of all three genes encoding laminin-332; its loss is thus implicated in the reduced or discontinuous deposition of the heterotrimeric basement membrane molecule as evident in carcinomas. Uncoupled expression of laminin genes, on the other hand, namely overexpression of the laminin-γ2 chain is an impressive marker at invasive edges of carcinomas where tumor cells are maximally exposed to signals from stromal cell types like macrophages. As Smad4 is characterized as an integrator of multiple extracellular stimuli in a strongly contextual manner, we asked if loss of Smad4 may also be involved in uncoupled expression of laminin genes in response to altered environmental stimuli. Here, we address Smad4 dependent effects of the prominent inflammatory cytokine TNFα on tumor cells.

Results

Smad4-reconstituted colon carcinoma cells like adenoma cells respond to TNFα with an increased expression of all three chains encoding laminin-332; coincubation with TGFβ and TNFα leads to synergistic induction and to the secretion of large amounts of the heterotrimer. In contrast, in Smad4-deficient cells TNFα can induce expression of the γ2 and β3 but not the α3 chain. Surprisingly, this uncoupled induction of laminin-332 chains in Smad4-negative cells rather than causing intracellular accumulation is followed by the release of γ2 into the medium, either in a monomeric form or in complexes with as yet unknown proteins. Soluble γ2 is associated with increased cell migration.

Conclusions

Loss of Smad4 may lead to uncoupled induction of laminin-γ2 in response to TNFα and may therefore represent one of the mechanisms which underlie accumulation of laminin-γ2 at the invasive margin of a tumor. The finding, that γ2 is secreted from tumor cells in significant amounts and is associated with increased cell migration may pave the way for further investigation to better understand its functional relevance for tumor progression.
Gamma knife radiosurgery for essential tremor: A Case report and review of the literature
Authors: Elaimy Ameer L , Demakas John J , Arthurs Benjamin J , Cooke Barton S , Fairbanks Robert K , Lamoreaux Wayne T , Mackay Alexander R , Greeley David R , Lee Christopher M
Published: March 2010

Approximately 5 million people in America are affected by essential tremors (ET), which are classified as a type of benign movement disorder. This disease manifests as tremors that usually occur in the hands, but they may also be present in the head, face, tongue, and lower limbs. Radiofrequency thalamotomy (RF) and deep brain stimulation (DBS) are common invasive procedures with proven track records that are used to treat ET. Although these procedures have high success rates, they still put patients at risk of potential side effects and are invasive by nature. Thalamotomy using the gamma knife (GK) also produces favorable outcomes in treating tremors, without the complications associated with invasive neurosurgery procedures. This report describes the presenting symptoms and extended treatment outcome for a patient with an advanced case of ET, who received GK thalamotomy treatment six years ago. Because of this non-invasive treatment, she regained the ability to paint and live with an improved quality of life. We also discuss and review the relevant literature regarding the risks and benefits of this treatment modality. GK thalamotomy is one effective option for the treatment of ET, and due to its noninvasive nature, it has a different risk profile than neurosurgery. We suggest that GK thalamotomy should be presented as one viable treatment option to all ET patients, and should be recommended to those who would be best served by less invasive treatment techniques.
Alterations in the steroid hormone receptor co-chaperone FKBPL are associated with male infertility: a case-control study
Authors: Sunnotel Olaf , Hiripi Laszlo , Lagan Kevin , McDaid Jennifer R , De León Johanny M , Miyagawa Yasushi , Crowe Hannah , Kaluskar Soniya , Ward Michael , Scullion Catherine , Campbell Alan , Downes CS , Hirst David , Barton David , Mocanu Edgar , Tsujimura Akira , Cox Marc B , Robson Tracy , Walsh Colum P
Published: March 2010

Background

Male infertility is a common cause of reproductive failure in humans. In mice, targeted deletions of the genes coding for FKBP6 or FKBP52, members of the FK506 binding protein family, can result in male infertility. In the case of FKBP52, this reflects an important role in potentiating Androgen Receptor (AR) signalling in the prostate and accessory glands, but not the testis. In infertile men, no mutations of FKBP52 or FKBP6 have been found so far, but the gene for FKBP-like (FKBPL) maps to chromosome 6p21.3, an area linked to azoospermia in a group of Japanese patients.

Methods

To determine whether mutations in FKBPL could contribute to the azoospermic phenotype, we examined expression in mouse and human tissues by RNA array blot, RT-PCR and immunohistochemistry and sequenced the complete gene from two azoospermic patient cohorts and matching control groups. FKBPL-AR interaction was assayed using reporter constructs in vitro.

Results

FKBPL is strongly expressed in mouse testis, with expression upregulated at puberty. The protein is expressed in human testis in a pattern similar to FKBP52 and also enhanced AR transcriptional activity in reporter assays. We examined sixty patients from the Japanese patient group and found one inactivating mutation and one coding change, as well as a number of non-coding changes, all absent in fifty-six controls. A second, Irish patient cohort of thirty showed another two coding changes not present in thirty proven fertile controls.

Conclusions

Our results describe the first alterations in the gene for FKBPL in azoospermic patients and indicate a potential role in AR-mediated signalling in the testis.
Characterization of the HIV-1 integrase chromatin- and LEDGF/p75-binding abilities by mutagenic analysis within the catalytic core domain of integrase
Authors: Zheng Yingfeng , Ao Zhujun , Jayappa Kallesh Danappa , Yao Xiaojian
Published: March 2010

Background

During the early stage of HIV-1 replication, integrase (IN) plays important roles at several steps, including reverse transcription, viral DNA nuclear import, targeting viral DNA to host chromatin and integration. Previous studies have demonstrated that HIV-1 IN interacts with a cellular Lens epithelium-derived growth factor (LEDGF/p75) and that this viral/cellular interaction plays an important role for tethering HIV-1 preintegration complexes (PICs) to transcriptionally active units of host chromatin. Meanwhile, other studies have revealed that the efficient knockdown and/or knockout of LEDGF/p75 could not abolish HIV infection, suggesting a LEDGF/p75-independent action of IN for viral DNA chromatin targeting and integration, even though the underlying mechanism(s) is not fully understood.

Results

In this study, we performed site-directed mutagenic analysis at the C-terminal region of the IN catalytic core domain responsible for IN/chromatin binding and IN/LEDGF/p75 interaction. The results showed that the IN mutations H171A, L172A and EH170,1AA, located in the loop region 170EHLK173 between the α4 and α5 helices of IN, severely impaired the interaction with LEDGF/p75 but were still able to bind chromatin. In addition, our combined knockdown approach for LEDGF/p75 also failed to dissociate IN from chromatin. This suggests that IN has a LEDGF/p75-independent determinant for host chromatin binding. Furthermore, a single-round HIV-1 replication assay showed that the viruses harboring IN mutants capable of LEDGF/p75-independent chromatin binding still sustained a low level of infection, while the chromatin-binding defective mutant was non-infectious.

Conclusions

All of these data indicate that, even though the presence of LEDGF/p75 is important for a productive HIV-1 replication, IN has the ability to bind chromatin in a LEDGF/p75-independent manner and sustains a low level of HIV-1 infection. Hence, it is interesting to define the mechanism(s) underlying IN-mediated LEDGF/p75-independent chromatin targeting, and further studies in this regard will help for a better understanding of the molecular mechanism of chromatin targeting by IN during HIV-1 infection.
An ethnobotanical survey of medicinal plants in Babungo, Northwest Region, Cameroon
Authors: Simbo David J
Published: March 2010

Background

An ethnobotanical survey was undertaken to record information on medicinal plants from traditional medical practitioners in Babungo and to identify the medicinal plants used for treating diseases.

Methods

Traditional Medical Practitioners (TMP's) who were the main informants were interviewed using semi-structured questionnaires and open-ended conversations. Field trips were made to the sites where TMP's harvest plants.

Results

The survey identified and recorded 107 plants species from 54 plant families, 98 genera used for treating diseases in Babungo. The Asteraceae was the most represented plant family while herbs made up 57% of the total medicinal plants used. The leaf was the most commonly used plant part while concoction and decoction were the most common method of traditional drug preparation. Most medicinal plants (72%) are harvested from the wild and 45% of these have other non medicinal uses. Knowledge of the use of plants as medicines remains mostly with the older generation with few youth showing an interest.

Conclusions

A divers number of plants species are used for treating different diseases in Babungo. In addition to their use as medicines, a large number of plants have other non medicinal uses. The youth should be encouraged to learn the traditional medicinal knowledge to preserve it from being lost with the older generation.
Does commitment to rehabilitation influence clinical outcome of total hip resurfacing arthroplasty?
Authors: Marker David R , Seyler Thorsten M , Bhave Anil , Zywiel Michael G , Mont Michael A
Published: March 2010

Background

The purpose of this study was to evaluate whether compliance and rehabilitative efforts were predictors of early clinical outcome of total hip resurfacing arthroplasty.

Methods

A cross-sectional survey was utilized to collect information from 147 resurfacing patients, who were operated on by a single surgeon, regarding their level of commitment to rehabilitation following surgery. Patients were followed for a mean of 52 months (range, 24 to 90 months). Clinical outcomes and functional capabilities were assessed utilizing the Harris hip objective rating system, the SF-12 Health Survey, and an eleven-point satisfaction score. A linear regression analysis was used to determine whether there was any correlation between the rehabilitation commitment scores and any of the outcome measures, and a multivariate regression model was used to control for potentially confounding factors.

Results

Overall, an increased level of commitment to rehabilitation was positively correlated with each of the following outcome measures: SF-12 Mental Component Score, SF-12 Physical Component Score, Harris Hip score, and satisfaction scores. These correlations remained statistically significant in the multivariate regression model.

Conclusions

Patients who were more committed to their therapy after hip resurfacing returned to higher levels of functionality and were more satisfied following their surgery.
Intravenous levosimendan-norepinephrine combination during off-pump coronary artery bypass grafting in a hemodialysis patient with severe myocardial dysfunction
Authors: Papadopoulos Georgios , Baikoussis Nikolaos G , Tzimas Petros , Siminelakis Stavros N , Karanikolas Menelaos
Published: March 2010

This the case of a 63 year-old man with end-stage renal disease (on chronic hemodialysis), unstable angina and significantly impaired myocardial contractility with low left ventricular ejection fraction, who underwent off-pump one vessel coronary bypass surgery. Combined continuous levosimendan and norepinephrine infusion (at 0.07 μg/kg/min and 0.05 μg/kg/min respectively) started immediately after anesthesia induction and continued for 24 hours. The levosimendan/norepinephrine combination helped maintain an appropriate hemodynamic profile, thereby contributing to uneventful completion of surgery and postoperative hemodynamic stability. Although levosimendan is considered contraindicated in ESRD patients, this case report suggests that combined perioperative levosimendan/norepinephrine administration can be useful in carefully selected hemodialysis patients with impaired myocardial contractility and ongoing myocardial ischemia, who undergo off-pump myocardial revascularization surgery.
Linking toxicant physiological mode of action with induced gene expression changes in Caenorhabditis elegans
Authors: Swain Suresh , Wren Jodie F , Stürzenbaum Stephen R , Kille Peter , Morgan A John , Jager Tjalling , Jonker Martijs J , Hankard Peter K , Svendsen Claus , Owen Jenifer , Hedley B Ann , Blaxter Mark , Spurgeon David J
Published: March 2010

Background

Physiologically based modelling using DEBtox (dynamic energy budget in toxicology) and transcriptional profiling were used inCaenorhabditis elegansto identify how physiological modes of action, as indicated by effects on system level resource allocation were associated with changes in gene expression following exposure to three toxic chemicals: cadmium, fluoranthene (FA) and atrazine (AZ).

Results

For Cd, the physiological mode of action as indicated by DEBtox model fitting was an effect on energy assimilation from food, suggesting that the transcriptional response to exposure should be dominated by changes in the expression of transcripts associated with energy metabolism and the mitochondria. While evidence for effect on genes associated with energy production were seen, an ontological analysis also indicated an effect of Cd exposure on DNA integrity and transcriptional activity. DEBtox modelling showed an effect of FA on costs for growth and reproduction (i.e. for production of new and differentiated biomass). The microarray analysis supported this effect, showing an effect of FA on protein integrity and turnover that would be expected to have consequences for rates of somatic growth. For AZ, the physiological mode of action predicted by DEBtox was increased cost for maintenance. The transcriptional analysis demonstrated that this increase resulted from effects on DNA integrity as indicated by changes in the expression of genes chromosomal repair.

Conclusions

Our results have established that outputs from process based models and transcriptomics analyses can help to link mechanisms of action of toxic chemicals with resulting demographic effects. Such complimentary analyses can assist in the categorisation of chemicals for risk assessment purposes.
A rational use of glucocorticoids in patients with early arthritis has a minimal impact on bone mass
Authors: Ibañez Monica , Ortiz Ana M , Castrejón Isabel , García-Vadillo J Alberto , Carvajal Inmaculada , Castañeda Santos , González-Álvaro Isidoro
Published: March 2010

Introduction

Glucocorticoid (GC)-induced osteoporosis is a frequent complication in patients with rheumatoid arthritis. However, little information exists about the consequences of GC use in patients with early arthritis. Here we describe the variables underlying the use of GC in early arthritis, as well as its effect on bone-mineral density.

Methods

Data from 116 patients in our early arthritis register were analyzed (90 women; median age, 52.5 years, interquartile range (IQR, 38.5-66); 6-month median disease duration at entry (IQR, 4-9)). In this register, the clinical and treatment information was recorded systematically, including the cumulative GC dose. Lumbar spine, hip, and forearm bone-mineral density (BMD) measurements were performed at entry and after a 2-year follow-up. A multivariate analysis was performed to establish the variables associated with the use of GCs, as well as those associated with variations in BMD.

Results

Of the patients with early arthritis studied, 67% received GCs during the 2-year follow-up. GCs were more frequently prescribed to elderly patients, those with higher basal disease activity and disability, and patients with positive rheumatoid factor. When adjusted for these variables, GCs were less frequently prescribed to female patients. The use of GCs was associated with an increase of BMD in the ultradistal region of the forearm, although it induced a significant loss of BMD in the medial region of the forearm. No relevant effect of GC was noted on the BMD measured at other locations.

Conclusions

The frequent use of GCs as a "bridge therapy" in patients with early arthritis does not seem to be associated with relevant loss of bone mass. Moreover, cumulative GC administration might be associated with an increase of juxtaarticular BMD.
2× genomes - depth does matter
Authors: Milinkovitch Michel C , Helaers Raphaël , Depiereux Eric , Tzika Athanasia C , Gabaldón Toni
Published: March 2010

Background

Given the availability of full genome sequences, mapping gene gains, duplications, and losses during evolution should theoretically be straightforward. However, this endeavor suffers from overemphasis on detecting conserved genome features, which in turn has led to sequencing multiple eutherian genomes with low coverage rather than fewer genomes with high-coverage and more even distribution in the phylogeny. Although limitations associated with analysis of low coverage genomes are recognized, they have not been quantified.

Results

Here, using recently developed comparative genomic application systems, we evaluate the impact of low-coverage genomes on inferences pertaining to gene gains and losses when analyzing eukaryote genome evolution through gene duplication. We demonstrate that, when performing inference of genome content evolution, low-coverage genomes generate not only a massive number of false gene losses, but also striking artifacts in gene duplication inference, especially at the most recent common ancestor of low-coverage genomes. We show that the artifactual gains are caused by the low coverage of genome sequence per se rather than by the increased taxon sampling in a biased portion of the species tree.

Conclusions

We argue that it will remain difficult to differentiate artifacts from true changes in modes and tempo of genome evolution until there is better homogeneity in both taxon sampling and high-coverage sequencing. This is important for broadening the utility of full genome data to the community of evolutionary biologists, whose interests go well beyond widely conserved physiologies and developmental patterns as they seek to understand the generative mechanisms underlying biological diversity.
Improved granular medium model for unconsolidated sands using coordination number, porosity, and pressure relations
Authors: Dutta Tanima , Mavko Gary , Mukerji Tapan
Published: March 2010

We have developed a recipe for using closed-form expressions of effective-medium models to predict velocities in unconsolidated sandstones. The commonly used Hertz-Mindlin effective-medium model for granular media often predicts elastic wave velocities that are higher, and [Formula: see text] ratios that are lower, than those observed in laboratory and well log measurements in unconsolidated sediments. We use the extended Walton model, which introduces a parameter [Formula: see text] to represent the fraction of grain contacts that are perfectly adhered. Using the extended Walton model with [Formula: see text] ranging from 0.3 to 1, we obtain new empirical relations between the coordination number (C), porosity, and pressure for P- and S-wave velocities by inverting dynamic measurements on dry, unconsolidated sands. We propose using the extended Walton model [Formula: see text] along with these new C-porosity and C-pressure relations to study the mechanical compaction of unconsolidated sandstones. The model has been tested on two experimental data sets. It provides a reasonable fit to observed P- and S-wave velocities and specifically improves shear-wave predictions.
Case history of combined airborne time-domain electromagnetics and power-line field survey in Chibougamau, Canada
Authors: Vallée Marc A. , Smith Richard S. , Keating Pierre
Published: March 2010

Exploration for volcanogenic massive sulfides requires good geologic understanding. Geologic knowledge often is limited by a lack of outcrops. This is especially true in Canada under residual glacial covers. Geologic information must therefore be complemented by information obtained using means such as geophysical and geochemical observations. Electromagnetic (EM) methods extend lithological understanding to depths beyond the overburden. Massive sulfides are highly conductive and, depending on their depth and volume, may be detected easily by airborne EM surveys. They are more often equant than graphitic sediments, which typically have longer strike length. Current EMtechniques that identify massive sulfides operate in the frequency or time domain, the latter being more common. Additional information can be provided by using power-line fields as a source of EM signals when the powerlines are appropriately located in the area of interest. We have worked in an active exploration area near Chibougamau, Canada, known for a large occurrence of massive sulfide deposits. The geology is a sequence of volcanic formations with felsic and mafic intrusions. Our magnetic technique responded well to mafic rocks. An airborne time-domain EM survey mapped localized and intrasedimentary conductors in that area. We learned in our study that power-line EM fields can be used to map large-extent conductive formations and narrow geologic faults.
Optimized Chebyshev Fourier migration: A wide-angle dual-domain method for media with strong velocity contrasts
Authors: Zhang Jin-Hai , Wang Wei-Min , Wang Shu-Qin , Yao Zhen-Xing
Published: March 2010

A wide-angle propagator is essential when imaging complex media with strong lateral velocity contrasts in one-way wave-equation migration. We have developed a dual-domain one-way propagator using truncated Chebyshev polynomials and a globally optimized scheme. Our method increases the accuracy of the expanded square-root operator by adding two high-order terms to the traditional split-step Fourier propagator. First, we approximate the square-root operator using Taylor expansion around the reference background velocity. Then, we apply the first-kind Chebyshev polynomials to economize the results of the Taylor expansion. Finally, we optimize the constant coefficients using the globally optimized scheme, which are fixed and feasible for arbitrary velocity models. Theoretical analysis and nu-merical experiments have demonstrated that the method has veryhigh accuracy and exceeds the unoptimized Fourier finite-difference propagator for the entire range of practical velocity contrasts. The accurate propagation angle of the method is always about 60° under the relative error of 1% for complex media with weak, moderate, and even strong lateral velocity contrasts. The method allows us to handle wide-angle propagations and strong lateral velocity contrast simultaneously by using Fourier transform alone. Only four 2D Fourier transforms are required for each step of 3D wavefield extrapolation, and the computing cost is similar to that of the Fourier finite-difference method. Compared with the finite-difference method, our method has no two-way splitting error (i.e., azimuthal-anisotropy error) for 3D cases and almost no numerical dispersion for coarse grids. In addition, it has strong potential to be accelerated when an enhanced fast Fourier transform algorithm emerges.
Multidisciplinary Meeting on Male Breast Cancer: Summary and Research Recommendations
Authors: Korde Larissa A. , Zujewski Jo Anne , Kamin Leah , Giordano Sharon , Domchek Susan , Anderson William F. , Bartlett John M.S. , Gelmon Karen , Nahleh Zeina , Bergh Jonas , Cutuli Bruno , Pruneri Giancarlo , McCaskill-Stevens Worta , Gralow Julie , Hortobagyi Gabriel , Cardoso Fatima
Published: March 2010

Male breast cancer is a rare disease, accounting for less than 1% of all breast cancer diagnoses worldwide. Most data on male breast cancer comes from small single-institution studies, and because of the paucity of data, the optimal treatment for male breast cancer is not known. This article summarizes a multidisciplinary international meeting on male breast cancer, sponsored by the National Institutes of Health Office of Rare Diseases and the National Cancer Institute Divisions of Cancer Epidemiology and Genetics and Cancer Treatment and Diagnosis. The meeting included representatives from the fields of epidemiology, genetics, pathology and molecular biology, health services research, and clinical oncology and the advocacy community, with a comprehensive review of the data. Presentations focused on highlighting differences and similarities between breast cancer in males and females. To enhance our understanding of male breast cancer, international consortia are necessary. Therefore, the Breast International Group and North American Breast Cancer Group have joined efforts to develop an International Male Breast Cancer Program and to pool epidemiologic data, clinical information, and tumor specimens. This international collaboration will also facilitate the future planning of clinical trials that can address essential questions in the treatment of male breast cancer.
High EVI1 Expression Predicts Outcome in Younger Adult Patients With Acute Myeloid Leukemia and Is Associated With Distinct Cytogenetic Abnormalities
Authors: Gröschel Stefan , Lugthart Sanne , Schlenk Richard F. , Valk Peter J.M. , Eiwen Karina , Goudswaard Chantal , van Putten Wim J.L. , Kayser Sabine , Verdonck Leo F. , Lübbert Michael , Ossenkoppele Gert-Jan , Germing Ulrich , Schmidt-Wolf Ingo , Schlegelberger Brigitte , Krauter Jürgen , Ganser Arnold , Döhner Hartmut , Löwenberg Bob , Döhner Konstanze , Delwel Ruud
Published: March 2010

Purpose

The purpose of this study was to investigate frequency and prognostic significance of high EVI1 expression in acute myeloid leukemia (AML).

Patients and Methods

A diagnostic assay detecting multiple EVI1 splice variants was developed to determine the relative EVI1 expression by single real-time quantitative polymerase chain reaction in 1,382 newly diagnosed adult patients with AML younger than 60 years. Patients were treated on four Dutch-Belgian HOVON (n = 458) and two German-Austrian AML Study Group protocols (n = 924).

Results

The EVI1 assay was tested in the HOVON cohort and validated in the AMLSG cohort. High EVI1 levels (EVI1+) were found with similar frequencies in both cohorts combined, with a 10.7% incidence (148 of 1,382). EVI1+ independently predicted low complete remission (CR) rate (odds ratio, 0.54; P = .002), adverse relapse-free survival (RFS; hazard ratio [HR], 1.32; P = .05), and event-free survival (EFS; HR, 1.46; P < .001). This adverse prognostic impact was more pronounced in the intermediate cytogenetic risk group (EFS; HR, 1.64; P < .001; and RFS; HR, 1.55; P = .02), and was also apparent in cytogenetically normal AML (EFS; HR, 1.67; P = .008). Besides inv(3)/t(3;3), EVI1+ was significantly associated with chromosome abnormalities monosomy 7 and t(11q23), conferring prognostic impact within these two cytogenetic subsets. EVI1+ was virtually absent in favorable-risk AML and AML with NPM1 mutations. Patients with EVI1+ AML (n = 28) who received allogeneic stem cell transplantation in first CR had significantly better 5-year RFS (33% ± 10% v 0%).

Conclusion

EVI1 expression in AML is unequally distributed in cytogenetic subtypes. It predicts poor outcome, particularly among intermediate cytogenetic risk AML. Patients with EVI1+ AML may benefit from allogeneic transplantation in first CR. Pretreatment EVI1 screening should be included in risk stratification.
Selective Modulation of Follicle-Stimulating Hormone Signaling Pathways with Enhancing Equine Chorionic Gonadotropin/Antibody Immune Complexes
Authors: Wehbi Vanessa , Decourtye Jérémy , Piketty Vincent , Durand Guillaume , Reiter Eric , Maurel Marie-Christine
Published: March 2010

The injection of equine chorionic gonadotropin (eCG) in dairy goats induces the production of anti-eCG antibodies (Abs) in some females. We have previously shown that Abs negatively modulate the LH and FSH-like bioactivities of eCG, in most cases, compromising fertility in treated females. Surprisingly, we found out that some anti-eCG Abs improved fertility and prolificity of the treated females, in vivo. These Abs, when complexed with eCG, enhanced LH and FSH ability to induce steroidogenesis on specific target cells, in vitro. In the present study, we analyzed the impact of three eCG/anti-eCG Ab-enhancing complexes on two transduction mechanisms triggered by the FSH receptor: guanine nucleotide-binding protein αS-subunit/cAMP/protein kinase A (PKA) and β-arrestin-dependent pathways, respectively. In all cases, significant enhancing effects were observed on ERK phosphorylation compared with eCG alone. However, cAMP production and PKA activation induced by eCG could be differently modulated by Abs. By using a pharmacological inhibitor of PKA and small interfering RNA-mediated knock-down of endogenous β-arrestin 1 and 2, we demonstrated that signaling bias was induced and was clearly dependent on the complexed Ab. Together, our data show that eCG/anti-eCG Ab-enhancing complexes can differentially modulate cAMP/PKA and β-arrestin pathways as a function of the complexed Ab. We hypothesize that enhancing Abs may change the eCG conformation, the immune complex acquiring new “biased” pharmacological properties ultimately leading to the physiological effects observed in vivo. The modulation of ligand pharmacological properties by Abs opens promising research avenues towards the optimization of glycoprotein hormone biological activities and, more generally, the development of new therapeutics.
The Action of Leptin on Appetite-Regulating Cells in the Ovine Hypothalamus: Demonstration of Direct Action in the Absence of the Arcuate Nucleus
Authors: Qi Yue , Henry Belinda A. , Oldfield Brian J. , Clarke Iain J.
Published: March 2010

It is widely accepted that leptin acts on first-order neurons in the arcuate nucleus (ARC) with information then relayed to other hypothalamic centers. However, the extent to which leptin mediates its central actions solely, or even primarily, via this route is unclear. We used a model of hypothalamo-pituitary disconnection (HPD) to determine whether leptin action on appetite-regulating systems requires the ARC. This surgical preparation eliminates the ARC. We measured effects of iv leptin to activate hypothalamic neurons (Fos labeling). In ARC-intact animals, leptin increased the percentage of Fos-positive melanocortin neurons and reduced percentages of Fos-positive neuropeptide Y neurons compared with saline-treated animals. HPD itself increased Fos labeling in the lateral hypothalamic area (LHA). Leptin influenced Fos labeling in the dorsomedial nucleus (DMH), ventromedial nucleus, and paraventricular nucleus (PVN) in HPD and normal animals, with effects on particular cell types varying. In the LHA and DMH, leptin decreased orexin cell activation in HPD and ARC-intact sheep. HPD abolished leptin-induced expression of Fos in melanin-concentrating hormone cells in the LHA and in CRH cells in the PVN. In contrast, HPD accentuated activation in oxytocin neurons. Our data from sheep with lesions encompassing the ARC do not suggest a primacy of action of leptin in this nucleus. We demonstrate that first order to second order signaling may not represent the predominant means by which leptin acts in the brain to generate integrated responses. We provide evidence that leptin exerts direct action on cells of the DMH, ventromedial nucleus, and PVN.
The Remaking of a Small College English Department
Authors: McDougal Stuart Y.
Published: March 2010

In 1998, Stuart McDougal was recruited by Macalester College to create a new English department to replace one that had been decimated by a series of retirements. McDougal accepted the challenge and immediately confronted a series of questions: What should the curriculum of a liberal arts English department look like at the end of the twentieth century and the beginning of the twenty-first? Who should be hired and what should they teach? How should one balance teaching and scholarship at a liberal arts college? What lessons could be drawn from experience at a large research university for the very different environment of a small liberal arts college? McDougal addresses these questions (and more) in his essay, “The Remaking of a Small College English Department.”
Where I Teach
Authors: Conlogue William
Published: March 2010

Opening a window on a small department in a medium-sized comprehensive Catholic university, this essay describes how the Marywood English department has wrestled with the challenges of a changing institutional culture, one that has moved from an emphasis on teaching and service to one focused on teaching and publication. The department's response has been a rededication to its long-standing commitment to quality instruction and service.
Una problemática convivencia entre representación y realidad en El nuevo Rey Gallinato y ventura por desgracia de Andrés de Claramonte
Authors: Domínguez-Hermida Beatriz
Published: March 2010

En El nuevo Rey Gallinato y la ventura por desgracia , Andrés de Claramonte adopta las doctrinas de la "enseñanza para príncipes" con el objetivo de señalar la discrepancia entre ideología (lo que debía ser un monarca) y la realidad (la monarquía de Felipe III). La distancia entre discurso y realidad no podía pasar desapercibida al espectador de la época y, por ello, tampoco debe ser inadvertido para la crítica, pues proporciona una clave de lectura fundamental. De esta manera, considero que las alusiones a Felipe III no constituyen una alabanza o ensalzamiento del mismo sino que, mediante su comparación con Gallinato, se marcan sus carencias y fallos. La crítica dirigida al soberano español reside en la exposición de dicha distancia. Por último, en la obra del dramaturgo murciano se contraponen dos espacios (las Indias frente a la península) con dos tipos de nobleza y, por tanto, con dos tipos de jerarquía social diferentes: la sanguínea y la monetaria. De este contraste nace la denuncia hacia una España viciada y pervertida por el dinero y la mentalidad burguesa.
Lara impugna a Vera Tassis: ¿Qué comedia atribuida a Salazar y Torres es de Cuero y Tapia?
Authors: O'Connor Thomas Austin
Published: March 2010

In 1684, Gaspar Agustín de Lara published his Obelisco fúnebre … a la inmortal memoria de D. Pedro Calderón de la Barca . In this eulogy of the great dramatist, he criticized severely Juan de Vera Tassis y Villarroel's editing skills and enumerated some of his serious failures of judgment. He included, in the latter category, one of Vera's earlier editorial projects, the publication in two volumes of the Cítara de Apolo the complete poetic and dramatic works of Agustín de Salazar y Torres. He singled out for particular criticism Vera's inclusion of Juan de Jáuregui's Orfeo , in the first volume, and an unnamed play by Cuero y Tapia, in the second. After reviewing the history of the textual transmission of Salazar's plays, I have concluded, based on historical and stylistic evidence, that the last play in the second volume, Triunfo y venganza de Amor , is not by Salazar and should now be attributed to Cuero y Tapia. It would appear that even Vera himself had some doubt regarding Triunfo . When one examines the signatures of the second volume of the Cítara de Apolo , it is clear that the play, the ninth, was added at the last moment and after the eight plays that were to comprise the original volume had been set and printed.
"Un borrón de la luz pura": La mirada en La estrella de Sevilla
Authors: Armas Austria Ramiro
Published: March 2010

Mi trabajo analiza los modos en que La estrella de Sevilla despliega puntualmente las creencias sobre el poder de la mirada como constructora de la acción dramática. Se trata de una mirada que se extiende al sentido acústico formando una esfera de sentidos. Pero además, es una mirada que contagia y produce una sintomatología creativa y destructora a la vez. Es el mal de ojo que se asemeja a la melancolía del amor cortés, pero que en la forma de la envidia adquiere dimensiones devastadoras, un eclecticismo heredado de las tradiciones arabo-islámicas, cuyo entendimiento es axial para la comprensión de la producción literaria del Siglo de Oro español. Así pues, en este trabajo intento elucidar las diferencias entre las miradas de los personajes que determinan un orden masculino preestablecido y la mirada femenina de la protagonista como espacio de indeterminación que se desborda y fragmenta toda vez que desata los efectos del mal de ojo.
Gaius Caligula's Mental Illness
Authors: Sidwell Barbara
Published: March 2010

The strange behavior of the emperor Gaius has been the subject of debate for many historians. Some charge him with madness and attribute it to his illness in A.D. 37, whereas others believe it occurred later, or else had nothing to do with his sickness. We have no real evidence to reconstruct his mental state. Therefore speculations about madness are fruitless, as they can't be proven. Also, his madness belongs to a discourse which originates mainly from the senatorial narrative that sought to discredit him through any means possible. Thus, his acts should be seen from other angles, and the search for "mad Caligula" abandoned.
"Page and Stage": The Actor's Perspective
Authors: Buxton John , Painter Jay
Published: March 2010

As actors who toured the country in the spring of 2009 performing in The Iliad: Book One with the Aquila Theatre Company as part of the "Page and Stage" program, we here discuss some of the challenges and rewards of making Homer's poetry accessible. We found that despite diverse audiences, certain reactions and impressions emerged as patterns. Additionally, we discovered that, just as the audiences were impacted by the performance, we as actors grew in understanding of our craft and our own humanity.
"Page and Stage": Theater, Tradition, and Culture in America
Authors: Meineck Peter
Published: March 2010

"Page and Stage: Theater, Tradition, and Culture in America" was a major classics-based public program supported by the National Endowment for the Humanities that toured the United States in 2008-9. This paper traces the origins and development of this groundbreaking new program that united professional theater artists with classicists and librarians to reach an audience of over 88,000 people and sought to inspire dynamic public programming between American libraries and performing arts centers. The program was based around Homer's Iliad and involved performances, lectures, reading groups, film screenings, post-performance discussions, free books, and a new Web site ( www.pageandstage.org ).
Seismic Performance Tests of Masonry and Masonry Veneer
Authors: Klingner Richard E. , Shing P. Benson , McGinley W. Mark , McLean David I. , Okail Hussein , Jo Seongwoo
Published: March 2010

This paper summarizes the preliminary findings of a research project on performance-based design of masonry and masonry veneer. The project includes quasi-static testing of clay masonry veneer with wood-stud and concrete masonry backings; shaking-table tests of concrete masonry and wood-stud wall segments with clay masonry veneer; and shaking-table tests of a full-scale wood-stud structure with clay masonry veneer and a concrete masonry structure with clay masonry veneer; and nonlinear analytical modeling. Based on the test results, recommendations are presented for refinements to current seismic design and detailing provisions for masonry and masonry veneer.
Skiing and Boarding Injuries on Norwegian Slopes during Two Winter Seasons
Authors: Ekeland Arne , Rødven Andreas
Published: March 2010

A central ski patrol-based registration of skiing and boarding injuries was performed by the Norwegian Ski Lift Association during the winter seasons of 2006/2007 and 2007/2008. A total of 8149 injured skiers/boarders and 6.024 million skier/boarder days were recorded during the two seasons, giving an injury rate of 1.35 injured per 1000 skier/boarder days. Most of the injuries occurred during alpine skiing (64 %) and snowboarding (31 %), compared to telemark skiing (2 %) and skiboarding (3 %). Wrist injuries were common among injured snowboarders (25 %) compared to 4–6 % for the others (P<0.001). The knee was the main injury location in alpine skiers (25 %) compared to 21 % among skiboarders, 19 % among telemarkers, and only 8 % among snowboarders (P<0.001). The percentage of knee injuries in females (30 %) was almost twice as high as for males (16 %) (P<0.001), whereas shoulder injuries was twice as high in males (16 %) as in females (7 %) (P<0.001). As percent of all injuries injured snowboarders suffered more fractures (30 %) than skiboarders (27 %), alpine (22 %), and telemark skiers (18 %) (P<0.001), but fracture of the lower leg was uncommon among snowboarders (0.5 %) and telemarkers (0.6 %) compared to alpine skiers (6 %) and skiboarders (9 %) (P<0.001). Lower leg fractures accounted for 5 % of the injured alpine skiers 20 years and older, 3 % for adolescents aged 13–19 years compared to 12 % for children 12 years and younger (P<0.001). Nineteen percent of the skiers/boarders were injured in terrain parks. They suffered more fractures and back injuries than those injured at other locations (P<0.001). Fifty-seven percent of injured skiers/boarders used helmet, and they had a lower prevalence of head injuries (15.9 %) than those without helmet (18.2 %) (P<0.01). In conclusion, injured alpine skiers were most prone to knee injuries, and skiboarders to lower leg fractures. This fracture was still a common injury for children in these two disciplines. Injured snowboarders were most prone to suffer wrist injuries. The prevalence of knee injuries among females was almost twice that of males, whereas the reverse was observed for shoulder injuries. Injured skiers/boarders wearing a helmet had a lower prevalence of head injuries than those without helmet.