bluuebunny/crossref_metadata_2025 huggingface dataset:
Thinking Aloud to Create Better Condom Use Questions
Authors: Edwards Mildred , Thomsen Sarah C. , Toroitich-Ruto Cathy
Published: March 2005

Measuring the effects of HIV/AIDS prevention efforts through self-reported condom use data is problematic since such data are frequently subject to bias. The purpose of this study was to pretest a sexual behavior instrument to identify ways to improve comprehension and decrease recall and social desirability bias. The method used was cognitive interviewing, in which fifteen sex workers were asked to “think aloud” as they problem solved simulated tasks. Results indicated that (1) a lexicon of culturally appropriate terms for sex and partner types should be provided to interviewers, (2) recall of sexual behavior may be aided by using grids to record information, and (3) social desirability may be decreased if trust is established with the participants. Using the “think aloud” method to pretest instruments may help improve the validity of self-reported sex acts, but only more objective measures of condomuse may help to quantify such improvements.
Ethnography and Experiments: Cultural Models and Expertise Effects Elicited with Experimental Research Techniques
Authors: Ross Norbert , Medin Douglas L.
Published: March 2005

This article reports the results of two independent studies dealing with saliency effects within the domain of folkbiological knowledge. In study 1, the authors present data from a free-listing task that explored tree-name generation among Tzotzil Maya of Zinacantán (Chiapas). Study 2 compares Menominee Native Americans with majority culture (nonprofessional) fish experts in central Wisconsin. The studies explore patterns of informant agreement and disagreement, looking at the accessibility of certain kinds of biological knowledge, both within and across cultural groups. The authors show that differences in levels of expertise and practice, as well as habitual patterns of knowledge organization (spontaneous categorization), can lead to significant differences in the salience or accessibility of certain types of knowledge.
Constitutively activated FGFR3 mutants signal through PLCγ-dependent and -independent pathways for hematopoietic transformation
Authors: Chen Jing , Williams Ifor R. , Lee Benjamin H. , Duclos Nicole , Huntly Brian J. P. , Donoghue Daniel J. , Gilliland D. Gary
Published: March 2005

Ectopic expression of fibroblast growth factor receptor 3 (FGFR3) associated with t(4;14) has been implicated in the pathogenesis of human multiple myeloma. Some t(4;14) patients have activating mutations of FGFR3, of which a minority are K650E (thanatophoric dysplasia type II [TDII]). To investigate the role of autophosphorylated tyrosine residues in FGFR3 signal transduction and transformation, we characterized a series of FGFR3 TDII mutants with single or multiple Y→F substitutions. Phenylalanine substitution of Y760, essential for phospholipase Cγ (PLCγ) binding and activation, significantly attenuated FGFR3 TDII–mediated PLCγ activation, as well as transformation in Ba/F3 cells and a murine bone marrow transplant leukemia model. In contrast, single substitution of Y577, Y724, or Y770 had minimal to moderate effects on TDII-dependent transformation. Substitution of all 4 non–activation loop tyrosine residues significantly attenuated, but did not abolish, TDII transforming activity. Similar observations were obtained in the context of a constitutively activated fusion TEL-FGFR3 associated with t(4;12)(p16;p13) peripheral T-cell lymphomas. Moreover, 2 independent EμSR-FGFR3 TDII transgenic mouse lines developed a pro-B-cell lymphoma, and PLCγ was highly activated in primary lymphoma cells as assessed by tyrosine phosphorylation. These data indicate that engagement of multiple signaling pathways, including PLCγ-dependent and PLCγ-independent pathways, is required for full hematopoietic transformation by constitutively activated FGFR3 mutants.
A critical function for B-Raf at multiple stages of myelopoiesis
Authors: Kamata Tamihiro , Kang Jing , Lee Tzong-Hae , Wojnowski Leszek , Pritchard Catrin A. , Leavitt Andrew D.
Published: March 2005

Raf kinases play an integral role in the classic mitogen-activated protein (MAP) kinase (Raf/MEK/extracellular signal-related kinase [ERK]) intracellular signaling cascade, but their role in specific developmental processes is largely unknown. Using a genetic approach, we have identified a role for B-Raf during hematopoietic progenitor cell development and during megakaryocytopoiesis. Fetal liver and in vitro embryonic stem (ES) cell–derived myeloid progenitor development is quantitatively impaired in the absence of B-Raf. Biochemical data suggest that this phenotype is due to the loss of a normally occurring rise in B-Raf expression and associated ERK1/2 activation during hematopoietic progenitor cell formation. However, the presence of B-raf–/– ES cell–derived myeloid progenitors in the bone marrow of adult chimeric mice indicates the lack of an obligate cell-autonomous requirement for B-Raf in myeloid progenitor development. The lack of B-Raf also impairs megakaryocytopoiesis. Thrombopoietin (Tpo)–induced in vitro expansion of ES cell–derived megakaryocyte-lineage cells fails to occur in the absence of B-Raf. Moreover, this quantitative in vitro defect in megakaryocyte-lineage expansion is mirrored by chimeric mice data that show reduced B-raf–/– genotype contribution in megakaryocytes relative to its contribution in myeloid progenitors. Together, these data suggest that B-Raf plays a cell-autonomous role in megakaryocytopoiesis and a permissive role in myeloid progenitor development.
Association of klotho, bone morphogenic protein 6, and annexin A2 polymorphisms with sickle cell osteonecrosis
Authors: Baldwin Clinton , Nolan Vikki G. , Wyszynski Diego F. , Ma Qian-Li , Sebastiani Paola , Embury Stephen H. , Bisbee Alice , Farrell John , Farrer Lindsay , Steinberg Martin H.
Published: March 2005

In patients with sickle cell disease, clinical complications including osteonecrosis can vary in frequency and severity, presumably due to the effects of genes that modify the pathophysiology initiated by the sickle mutation. Here, we examined the association of single nucleotide polymorphisms (SNPs) in candidate genes (cytokines, inflammation, oxidant stress, bone metabolism) with osteonecrosis in patients with sickle cell disease. Genotype distributions were compared between cases and controls using multiple logistic regression techniques. An initial screen and follow-up studies showed that individual SNPs and haplotypes composed of several SNPs in bone morphogenic protein 6, annexin A2, and klotho were associated with sickle cell osteonecrosis. These genes are important in bone morphology, metabolism, and vascular disease. Our results may provide insight into the pathogenesis of osteonecrosis in sickle cell disease, help identify individuals who are at high risk for osteonecrosis, and thus allow earlier and more effective therapeutic intervention.
A cell behavior screen: identification, sorting, and enrichment of cells based on motility
Authors: Windler-Hart Sarah L , Chen Kwan Y , Chenn Anjen
Published: March 2005

Background

Identifying and isolating cells with specific behavioral characteristics will facilitate the understanding of the molecular basis regulating these behaviors. Although many approaches exist to characterize cell motility, retrieving cells of specific motility following analysis remains challenging.

Results

Cells migrating on substrates coated with fluorescent microspheres generate non-fluorescent tracks as they move and ingest the spheres. The area cleared by each cell allows for quantitation of single cell and population motility; because individual cell fluorescence is proportional to motility, cells can be sorted according to their degree of movement. Using this approach, we sorted a glioblastoma cell line into high motility and low motility populations and found stable differences in motility following sorting.

Conclusion

We describe an approach to identify, sort, and enrich populations of cells possessing specific levels of motility. Unlike existing assays of cell motility, this approach enables recovery of characterized cell populations, and can enable screens to identify factors that might regulate motility differences even within clonal population of cells.
Do Indonesian medical practitioners approve the availability of emergency contraception over-the-counter? A survey of general practitioners and obstetricians in Jakarta
Authors: Syahlul Dyna E , Amir Lisa H
Published: March 2005

Background

Few studies have examined the attitude of medical practitioners towards the availability of emergency contraception (EC) without prescription. In Indonesia, EC (either Yuzpe regimen or Postinor-2) is available by prescription only. We aimed to examine the level of knowledge, attitudes and practices of medical practitioners in Indonesia about EC, in particular their attitudes to the availability of EC over-the-counter (OTC), using a questionnaire.

Methods

Data were collected by an anonymous structured questionnaire. Questionnaires were distributed to general practitioners in 36 Community Health Centres and 25 private clinics using stratified random sampling according to area in Jakarta, and to obstetricians practicising in 24 government and private hospitals and eight private clinics in Jakarta. Two hundred and five general practitioners and 142 obstetricians and gynaecologists participated; overall response rate was 75%.

Results

Although most participants were familiar with EC, only 22% received a very good knowledge score (4 or 5/5 answers correct), while 52% received a poor score (0–2/5 correct). Most participants did not support the OTC availability of EC (70%). Logistic regression identified that participants who prescribed EC had an Odds of 3.8 (95% CI 1.90, 7.73) of approving OTC EC, after adjustment for age and speciality.

Conclusion

Although many organisations are working towards OTC availability of EC, it needs to be recognized and addressed that doctors who do not prescribe EC are unlikely to support the increased availability of EC.
A genomic approach to investigate developmental cell death in woody tissues of Populustrees
Authors: Moreau Charleen , Aksenov Nikolay , Lorenzo Maribel García , Segerman Bo , Funk Christiane , Nilsson Peter , Jansson Stefan , Tuominen Hannele
Published: March 2005

Background

Poplar (Populus sp.) has emerged as the main model system for molecular and genetic studies of forest trees. A Populus expressed sequence tag (EST) database (POPULUSDB) was previously created from 19 cDNA libraries each originating from different Populus tree tissues, and opened to the public in September 2004. We used this dataset for in silico transcript profiling of a particular process in the woody tissues of the Populus stem: the programmed death of xylem fibers.

Results

One EST library in POPULUSDB originates from woody tissues of the Populus stem where xylem fibers undergo cell death. Analysis of EST abundances and library distribution within the POPULUSDB revealed a large number of previously uncharacterized transcripts that were unique in this library and possibly related to the death of xylem fibers. The in silico analysis was complemented by a microarray analysis utilizing a novel Populus cDNA array with a unigene set of 25,000 sequences.

Conclusions

In silico analysis, combined with the microarray analysis, revealed the usefulness of non-normalized EST libraries in elucidating transcriptional regulation of previously uncharacterized physiological processes. The data suggested the involvement of two novel extracellular serine proteases, nodulin-like proteins and an Arabidopsis thaliana OPEN STOMATA 1 (AtOST1) homolog in signaling fiber-cell death, as well as mechanisms responsible for hormonal control, nutrient remobilization, regulation of vacuolar integrity and autolysis of the dying fibers.
Evaluation of normal and neoplastic human mast cells for expression of CD172a (SIRPα), CD47, and SHP-1
Authors: Florian Stefan , Ghannadan Minoo , Mayerhofer Matthias , Aichberger Karl J , Hauswirth Alexander W , Schernthaner Gerit-Holger , Printz Dieter , Fritsch Gerhard , Böhm Alexandra , Sonneck Karoline , Krauth Maria-Theresa , Müller Michael R , Sillaber Christian , Sperr Wolfgang R , Bühring Hans-Jörg , Valent Peter
Published: March 2005

Signal regulatory proteins (SIRPs) and tyrosine phosphatases have recently been implicated in the control of receptor tyrosine kinase (RTK)-dependent cell growth. In systemic mastocytosis (SM), neoplastic cells are driven by the RTK KIT, which is mutated at codon 816 in most patients. We examined expression of SIRPα, SIRPα ligand CD47, and Src homology 2 domain-containing protein tyrosine phosphatase-1 (SHP-1), a tyrosine phosphatase-type, negative regulator of KIT-dependent signaling, in normal human lung mast cells (HLMC) and neoplastic MC obtained from nine patients with SM. As assessed by multicolor flow cytometry, normal LMC expressed SIRPα, CD47, and SHP-1. In patients with SM, MC also reacted with antibodies against SIRPα and CD47. By contrast, the levels of SHP-1 were low or undetectable in MC in most cases. Corresponding data were obtained from mRNA analysis. In fact, whereas SIRPα mRNA and CD47 mRNA were detected in all samples, the levels of SHP-1 mRNA varied among donors. To demonstrate adhesive functions for SIRPα and CD47 on neoplastic MC, an adhesion assay was applied using the MC leukemia cell line HMC-1, which was found to bind to immobilized extracellular domains of SIRPα1 (SIRPα1ex) and CD47 (CD47ex), and binding of these cells to CD47ex was inhibited by the CD172 antibody SE5A5. In summary, our data show that MC express functional SIRPα and CD47 in SM, whereas expression of SHP-1 varies among donors and is low compared with LMC. It is hypothesized that CD172 and CD47 contribute to MC clustering and that the “lack” of SHP-1 in MC may facilitate KIT-dependent signaling in a subgroup of patients.
Interplay between septin organization, cell cycle and cell shape in yeast
Authors: Gladfelter Amy S. , Kozubowski Lukasz , Zyla Trevin R. , Lew Daniel J.
Published: March 2005

Septins are conserved filament-forming proteins that assemble into cortical cytoskeletal structures in animal and fungal cells. Although rapid progress has been made into the functions of septins, the mechanisms governing their localization and organization remain mysterious. In Saccharomyces cerevisiae, Cdc42p organizes the septin cytoskeleton into a ring in preparation for bud formation, following which septins remain as a collar at the mother-bud neck. We have dissected the phenotype of cdc42V36T,K94E cells that display an aberrant cell shape correlated with the development of ectopic septin caps and rings within the bud. The results suggest that a well-assembled septin cortex plays a novel role in directing growth to shape the nascent bud, and that a disorganized septin cortex directs improper growth generating an aberrant neck. Conversely, we found that the elongated bud shape arising as a result of the morphogenesis checkpoint cell cycle delay that accompanies septin perturbation can feed back to exacerbate minor defects in septin organization, by maintaining a bud-tip-localized septin assembly activity that competes with the neck-localized septin cortex. Using this exacerbation as a tool, we uncovered septin organization defects in many mutants not previously known to display such defects, expanding the cast of characters involved in proper assembly of the septin cortex to include CLN1, CLN2, BNI1, BNI4, BUD3, BUD4 and BUD5.
Ramoplanin: A Lipoglycodepsipeptide Antibiotic
Authors: Farver Debra K , Hedge Dennis D , Lee Steven C
Published: March 2005

OBJECTIVE:

To review the pharmacology, antimicrobial activity, pharmacokinetics, clinical applications, and safety of ramoplanin, a lipoglycodepsipeptide antibiotic.

DATA SOURCES:

Information was obtained from MEDLINE and BIOSIS databases (1984–August 2004) and Oscient Pharmaceu ticals using the key words ramoplanin, A 16686, A 16686A, and MDL 62198.

STUDY SELECTION AND DATA EXTRACTION:

Available English-based articles and abstracts were reviewed, along with information from Oscient Pharmaceuticals.

DATA SYNTHESIS:

Ramoplanin exerts its bactericidal activity against gram-positive aerobic and anaerobic bacteria by blocking peptidoglycan synthesis via lipid II. In vitro susceptibility reports have demonstrated efficacy against antibiotic-resistant gram-positive pathogens. Cross-resistance has not been documented with vancomyin and other glycopeptides. Clinical trials are investigating ramoplanin's oral administration for treatment of Clostridium difficile–associated diarrhea. Previous clinical trials had evaluated the suppression of colonization of vancomycin-resistant Enterococcus with ramoplanin. Adverse effects are minimal, and drug—drug interactions have not been documented.

CONCLUSIONS:

The completion of clinical trials will determine whether ramoplanin has a promising role as a treatment option for diarrhea due to C. difficile.
Successful Desensitization to Oxaliplatin
Authors: Lydia  , Fernando Nishan H , Hurwitz Hurbert I , Morse Michael A
Published: March 2005

OBJECTIVE:

To report the successful desensitization of a patient to oxaliplatin utilizing an 8-hour desensitization regimen in a controlled environment.

CASE SUMMARY:

A 53-year-old white woman with metastatic colon cancer was receiving oxaliplatin, bevacizumab, and capecitabine every 2 weeks, with a partial response to therapy. On her fifth cycle of this regimen, she experienced diaphoresis, hypotension, nausea, abdominal cramping, and coryza. According to the Naranjo probability scale, oxaliplatin, and not bevacizumab, was the probable cause of the hypersensitivity reaction. The woman continued therapy with capecitabine and bevacizumab, resulting in stable disease. Due to her initial response to the oxaliplatin-based regimen, it was decided to attempt desensitization to oxaliplatin in a controlled, inpatient environment. An 8-hour desensitization schedule was employed, and the patient successfully completed an additional 3 cycles with full-dose oxaliplatin.

DISCUSSION:

Hypersensitivity reactions to platinum-containing compounds are well described and potentially life threatening. With expanded use of oxaliplatin in various malignancies, an increased number of hypersensitivity reactions will likely be reported. Patients with previous hypersensitivity reactions to carboplatin are at risk for similar reactions to oxaliplatin. We achieved successful desensitization for oxaliplatin using increased concentrations of the drug over an 8-hour period concomitant with oral and intravenous corticosteroids and histamine blockers.

CONCLUSIONS:

Hypersensitivity reactions to platinum compounds may result in discontinuation of active therapies in patients with metastatic disease. Desensitization to oxaliplatin is possible utilizing this approach.
Recombinant Factor VIIa in the Treatment of Non-Hemophiliac Bleeding
Authors: Lam Masha SH , Sims-McCallum Rosalyn P
Published: March 2005

OBJECTIVE:

To review the clinical evidence for the use of recombinant factor VIIa (rFVIIa) in the prevention and/or treatment of bleeding in non-hemophiliac patients.

DATA SOURCES:

A MEDLINE search (1966–December 2004) was conducted to identify pertinent literature. Results were limited to English-language reports and clinical trials. References of relevant articles and selected abstracts presented at scientific meetings were also reviewed.

STUDY SELECTION AND DATA EXTRACTION:

Human data from prospective and retrospective studies that examined the hemostatic effect of rFVIIa in non-hemophiliac patients were reviewed, with a focus on surgical prophylaxis, liver disease, intractable bleeding associated with trauma and surgery, and anticoagulation reversal.

DATA SYNTHESIS:

Results from limited controlled trials on the use of rFVIIa as an adjunct for prevention of bleeding in surgery and liver diseases have not been consistent. For treatment of intractable bleeding, earlier use of rFVIIa in one trauma trial was shown to decrease the number of blood transfusions, but no differences in terms of clinical outcomes were observed in all trials. Controlled trials do not suggest an increased risk of thrombotic events. Optimal dosing and timing of administration have yet to be defined.

CONCLUSIONS:

Until further prospective controlled data are available, it is recommended that conventional intervention for prevention and control of hemorrhage in non-hemophiliac patients should remain the standard of care. Close monitoring of coagulation parameters is recommended before, during, and after therapy, especially in high-risk patients. Pharmacoeconomic analysis may be useful to help control costs and maximize clinical benefits.
Differences in Transmission Properties and Susceptibility to Long-Term Depression Reveal Functional Specialization of Ascending Axon and Parallel Fiber Synapses to Purkinje Cells
Authors: Sims Robert E. , Hartell Nicholas A.
Published: March 2005

An understanding of the patterns of mossy fiber transmission to Purkinje cells, via granule cell axons, is fundamental to models of cerebellar cortical signaling and processing. Early theories assumed that mossy fiber input is widely disseminated across the cerebellar cortex along beams of parallel fibers, which spread for several millimeters across the cerebellar cortex. Direct evidence for this has, however, proved controversial, leading to the development of an alternative hypothesis that mossy fiber inputs to the cerebral cortex are in fact vertically organized such that the ascending segment of the granule axon carries a greater synaptic weight than the parallel fiber segment. Here, we report that ascending axon synapses are selectively resistant to cerebellar long-term depression and that they release transmitter with higher mean release probabilities and mean quantal amplitudes than parallel fiber synapses. This novel specialization of synapses formed by different segments of the same axon not only explains the reported patterns of granule cell→ Purkinje cell transmission across the cerebellar cortex but also reveals an additional level of functionality and complexity of cerebellar processing. Consequently, ascending axon synapses represent a new element of cortical signal processing that should be distinguished from parallel fiber synapses in future experimental and theoretical studies of cerebellar function.
Deleted in Colorectal Cancer Binding Netrin-1 Mediates Cell Substrate Adhesion and Recruits Cdc42, Rac1, Pak1, and N-WASP into an Intracellular Signaling Complex That Promotes Growth Cone Expansion
Authors: Shekarabi Masoud , Moore Simon W. , Tritsch Nicolas X. , Morris Stephen J. , Bouchard Jean-Francois , Kennedy Timothy E.
Published: March 2005

Extracellular cues direct axon extension by regulating growth cone morphology. The netrin-1 receptor deleted in colorectal cancer (DCC) is required for commissural axon extension to the floor plate in the embryonic spinal cord. Here we demonstrate that challenging embryonic rat spinal commissural neurons with netrin-1, either in solution or as a substrate, causes DCC-dependent increases in growth cone surface area and filopodia number, which we term growth cone expansion. We provide evidence that DCC influences growth cone morphology by at least two mechanisms. First, DCC mediates an adhesive interaction with substrate-bound netrin-1. Second, netrin-1 binding to DCC recruits an intracellular signaling complex that directs the organization of actin. We show that netrin-1-induced growth cone expansion requires Cdc42 (cell division cycle 42), Rac1 (Ras-related C3 botulinum toxin substrate 1), Pak1 (p21-activated kinase), and N-WASP (neuronal Wiskott-Aldrich syndrome protein) and that the application of netrin-1 rapidly activates Cdc42, Rac1, and Pak1. Furthermore, netrin-1 recruits Cdc42, Rac1, Pak1, and N-WASP into a complex with the intracellular domain of DCC and Nck1. These findings suggest that DCC influences growth cone morphology by acting both as a transmembrane bridge that links extracellular netrin-1 to the actin cytoskeleton and as the core of a protein complex that directs the organization of actin.
A Model for Interaural Time Difference Sensitivity in the Medial Superior Olive: Interaction of Excitatory and Inhibitory Synaptic Inputs, Channel Dynamics, and Cellular Morphology
Authors: Zhou Yi , Carney Laurel H. , Colburn H. Steven
Published: March 2005

This study reports simulations of recent physiological results from the gerbil medial superior olive (MSO) that reveal that blocking glycinergic inhibition can shift the tuning for the interaural time difference (ITD) of the cell (Brand et al., 2002). Our simulations indicate that the model proposed in the study by Brand et al. (2002) requires precisely timed, short-duration inhibition with temporal accuracy exceeding that described in the auditory system. An alternative model is proposed that incorporates two anatomic observations in the MSO: (1) the axon arises from the dendrite that receives ipsilateral inputs; and (2) inhibitory synapses are located primarily on the soma in adult animals. When the inhibitory currents are activated or blocked, the model cell successfully simulates experimentally observed shifts in the best ITD. The asymmetrical cell structure allows an imbalance between the ipsilateral and contralateral excitatory inputs and shifts the ITD curve such that the best ITD is not at zero. Fine adjustment of the best ITD is achieved by the interplay of somatic sodium currents and synaptic inhibitory currents. The shift of the best ITD in the model is limited to ∼0.2 ms, which is behaviorally significant with respect to ITDs encountered in perceptual tasks. The model suggests a mechanism for dynamically “fine-tuning” the ITD sensitivity of MSO cells by the opponency between depolarizing sodium currents and hyperpolarizing inhibitory currents.
Selective Blockade of the Capsaicin Receptor TRPV1 Attenuates Bone Cancer Pain
Authors: Ghilardi Joseph R. , Röhrich Heidi , Lindsay Theodore H. , Sevcik Molly A. , Schwei Matthew J. , Kubota Kazufumi , Halvorson Kyle G. , Poblete Jeannie , Chaplan Sandra R. , Dubin Adrienne E. , Carruthers Nicholas I. , Swanson Devin , Kuskowski Michael , Flores Christopher M. , Julius David , Mantyh Patrick W.
Published: March 2005

Cancer colonization of bone leads to the activation of osteoclasts, thereby producing local tissue acidosis and bone resorption. This process may contribute to the generation of both ongoing and movement-evoked pain, resulting from the activation of sensory neurons that detect noxious stimuli (nociceptors). The capsaicin receptor TRPV1 (transient receptor potential vanilloid subtype 1) is a cation channel expressed by nociceptors that detects multiple pain-producing stimuli, including noxious heat and extracellular protons, raising the possibility that it is an important mediator of bone cancer pain via its capacity to detect osteoclast- and tumor-mediated tissue acidosis. Here, we show that TRPV1 is present on sensory neuron fibers that innervate the mouse femur and that, in anin vivomodel of bone cancer pain, acute or chronic administration of a TRPV1 antagonist or disruption of the TRPV1 gene results in a significant attenuation of both ongoing and movement-evoked nocifensive behaviors. Administration of the antagonist had similar efficacy in reducing early, moderate, and severe pain-related responses, suggesting that TRPV1 may be a novel target for pharmacological treatment of chronic pain states associated with bone cancer metastasis.
An EssentialDrosophilaGlutamate Receptor Subunit That Functions in Both Central Neuropil and Neuromuscular Junction
Authors: Featherstone David E. , Rushton Emma , Rohrbough Jeffrey , Liebl Faith , Karr Julie , Sheng Qi , Rodesch Christopher K. , Broadie Kendal
Published: March 2005

ADrosophilaforward genetic screen for mutants with defective synaptic development identifiedbad reception(brec). Homozygousbrecmutants are embryonic lethal, paralyzed, and show no detectable synaptic transmission at the glutamatergic neuromuscular junction (NMJ). Genetic mapping, complementation tests, and genomic sequencing show thatbrecmutations disrupt a previously uncharacterized ionotropic glutamate receptor subunit, named here “GluRIID.” GluRIID is expressed in the postsynaptic domain of the NMJ, as well as widely throughout the synaptic neuropil of the CNS. In the NMJ of nullbrecmutants, all known glutamate receptor subunits are undetectable by immunocytochemistry, and all functional glutamate receptors are eliminated. Thus, we conclude that GluRIID is essential for the assembly and/or stabilization of glutamate receptors in the NMJ. In nullbrecmutant embryos, the frequency of periodic excitatory currents in motor neurons is significantly reduced, demonstrating that CNS motor pattern activity is regulated by GluRIID. Although synaptic development and molecular differentiation appear otherwise unperturbed in null mutants, viable hypomorphicbrecmutants display dramatically undergrown NMJs by the end of larval development, suggesting that GluRIID-dependent central pattern activity regulates peripheral synaptic growth. These studies reveal GluRIID as a newly identified glutamate receptor subunit that is essential for glutamate receptor assembly/stabilization in the peripheral NMJ and required for properly patterned motor output in the CNS.
The Retrograde Spread of Synaptic Potentials and Recruitment of Presynaptic Inputs
Authors: Antonsen Brian L. , Herberholz Jens , Edwards Donald H.
Published: March 2005

Lateral excitation is a mechanism for amplifying coordinated input to postsynaptic neurons that has been described recently in several species. Here, we describe how a postsynaptic neuron, the lateral giant (LG) escape command neuron, enhances lateral excitation among its presynaptic mechanosensory afferents in the crayfish tailfan. A lateral excitatory network exists among electrically coupled tailfan primary afferents, mediated through central electrical synapses. EPSPs elicited in LG dendrites as a result of mechanosensory stimulation spread antidromically back through electrical junctions to unstimulated afferents, summate with EPSPs elicited through direct afferent-to-afferent connections, and contribute to recruitment of these afferents. Antidromic potentials are larger if the afferent is closer to the initial input on LG dendrites, which could create a spatial filtering mechanism within the network. This pathway also broadens the temporal window over which lateral excitation can occur, because of the delay required for EPSPs to spread through the large LG dendrites. The delay allows subthreshold inputs to the LG to have a priming effect on the lateral excitatory network and lowers the threshold of the network in response to a second, short-latency stimulus. Retrograde communication within neuronal pathways has been described in a number of vertebrate and invertebrate species. A mechanism of antidromic passage of depolarizing current from a neuron to its presynaptic afferents, similar to that described here in an invertebrate, is also present in a vertebrate (fish). This raises the possibility that short-term retrograde modulation of presynaptic elements through electrical junctions may be common.
Induction of δ-Opioid Receptor Function in the Midbrain after Chronic Morphine Treatment
Authors: Hack Stephen P. , Bagley Elena E. , Chieng Billy C. H. , Christie MacDonald J.
Published: March 2005

δ-Opioid receptor (DOPr) activation fails to produce cellular physiological responses in many brain regions, including the periaqueductal gray (PAG), despite neural expression of high densities of the receptor. Previous histochemical studies have demonstrated that a variety of stimuli, including chronic morphine treatment, induce the translocation of DOPr from intracellular pools to the surface membrane of CNS neurons. PAG neurons in slices taken from untreated mice exhibited μ-opioid receptor (MOPr) but not DOPr-mediated presynaptic inhibition of GABAergic synaptic currents. In contrast, after 5-6 d of chronic morphine treatment, DOPr stimulation inhibited synaptic GABA release onto most neurons. Shorter exposure to morphinein vitro(upto 4 h) orin vivo(18 h) did not induce functional DOPr responses. DOPr-mediated presynaptic inhibition could not be induced in slices from untreated animals by increasing synaptic activityin vitrousing high extracellular potassium concentrations or activation of protein kinase A. Induction of functional DOPr signaling by chronic morphine required MOPr expression, because no DOPr receptor responses were observed in MOPr knock-out mice. DOPr agonists also had no effect on miniature IPSCs in β-arrestin-2 knock-out mice after chronic morphine. These results suggest that induction of DOPr-mediated actions in PAG by chronic morphine requires prolonged MOPr stimulation and expression of β-arrestin-2.
Disruption of Ephrin Signaling Associates with Disordered Axophilic Migration of the Gonadotropin-Releasing Hormone Neurons
Authors: Gamble John A. , Karunadasa Delicia K. , Pape Jean-Rémi , Skynner Michael J. , Todman Martin G. , Bicknell R. John , Allen Jeremy P. , Herbison Allan E.
Published: March 2005

Ephrin signaling is involved in repulsive and attractive interactions mediating axon guidance and cell-boundary formation in the developing nervous system. As a result of a fortuitous transgene integration event, we have identified here a potential role for EphA5 in the axophilic migration of gonadotropin-releasing hormone (GnRH) neurons from the nasal placode into the brain along ephrin-expressing vomeronasal axons. Transgene integration in the GNR23 mouse line resulted in a 26 kb deletion in chromosome 5, ∼67 kb 3′ toEpha5. This induced a profound, region-specific upregulation of EphA5 mRNA and protein expression in the developing mouse brain. The GnRH neurons in GNR23 mice overexpressed EphA5 from embryonic day 11, whereas ephrin A3 and A5 mRNA levels in olfactory neurons were unchanged. The GnRH neurons were found to be slow in commencing their migration from the olfactory placode and also to form abnormal clusters of cells on the olfactory axons, prohibiting their migration out of the nose. As a result, adult hemizygous mice had only 40% of the normal complement of GnRH neurons in the brain, whereas homozygous mice had <15%. This resulted in infertility in adult female homozygous GNR23 mice, suggesting that some cases of human hypogonadotropic hypogonadism may result from ephrin-related mutations. These data provide evidence for a role of EphA-ephrin signaling in the axophilic migration of the GnRH neurons during embryogenesis.
On homosexualities in Latin America (and other places)
Authors: Lancaster Roger N.
Published: March 2005

De Los Otros: Intimacy and Homosexuality Among Mexican Men. JOSEPH CARRIER. NY: Columbia University Press, Between Men— Between Women: Lesbian and Gay Studies. Lillian Faderman and Larry Gross, eds., 1995. xiv + 231 pp., references, appendix, index.

Latin American Male Homosexualities. STEPHEN O. MURRAY with additional contributions by Manuel Arboleda G. etal. Albuquerque: University of New Mexico Press, 1995. xvi + 304, references.
Yengoyan on Handler's Schneider on Schneider
Authors: Yengoyan Aram A.
Published: March 2005

Schneider on Schneider: The Conversion of the Jews and Other Anthropological Stories. DAVID M. SCHNEIDER as told to RICHARD HANDLER. Durham, NC: Duke University Press, 1995. ix + 241 pp., notes, index.
Ordered Universes: Approaches to the Anthropology of Religion
Authors: Stewart Charles
Published: March 2005

Ordered Universes: Approaches to the Anthropology of Religion. MORTON KLASS. Boulder, CO: Westview Press, 1995. xiv + 177 pp., notes, bibliography, Index.
Priestess, Mother, Sacred Sister: Religions Dominated by Women
Authors: Moerman Daniel E.
Published: March 2005

Priestess, Mother, Sacred Sister: Religions Dominated by Women. SUSAN STARR SERED. New York and Oxford: Oxford University Press, 1994. 330 pp., photographs, notes, references, index.
The Covenants with Earth and Rain: Exchange, Sacrifice, and Revelation in Mixtec Sociality
Authors: Watanabe John M.
Published: March 2005

The Covenants with Earth and Rain: Exchange, Sacrifice, and Revelation in Mixtec Sociality. JOHN MONAGHAN. Norman: University of Oklahoma Press, 1995. xvi + 394 pp., illustrations, tables, notes, bibliography, index.
1492–1992: American Indian Persistence and Resurgence
Authors: Wagoner Paula L.
Published: March 2005

1492–1992: American Indian Persistence and Resurgence. KARL KROEBER, ed. Durham, NC: Duke University Press, 1994. iv + 261 pp., appendixes, contributors, index.
Women and Power in Native North America
Authors: Long Valerie A.
Published: March 2005

Women and Power in Native North America. LAURA F. KLEIN and LILLIAN A. ACKERMAN, eds. Norman: University of Oklahoma Press, 1995. x + 294 pp., map, tables, notes, references, contributors, index.
Reinventing the American People: Unity and Diversity Today
Authors: Chock Phyllis Pease
Published: March 2005

Reinventing the American People: Unity and Diversity Today. ROBERT ROYAL, ed. Washington, DC: Ethics and Public Policy Center. Grand Rapids, Ml and Cambridge, MA: William B. Eerdman Publishing, 1995. vii + 304 pp., notes, index of names.
Komplekse Liv: Kulturel Mangfoldlghed i Danmark
Authors: Caulkins D. Douglas
Published: March 2005

Komplekse Liv: Kulturel Mangfoldlghed i Danmark. JOHN LIEP and KAREN FOG OLWIG, eds. Copenhagen: Akademlsk Foriag, 1994. 182 pp., bibliography, index.
A Green Estate: Restoring Independence in Madagascar
Authors: Merges A. Endre
Published: March 2005

A Green Estate: Restoring Independence in Madagascar. GILLIAN FEELEY‐HARNIK. Washington, DC: Smithsonian Institution Press, 1991. xxvii + 627 pp., figures, maps, plates, tables, appendixes, notes, glossary, references, index.
In the Realm of the Diamond Queen: MarginalIty In an Out‐of‐the‐Way Place
Authors: George Kenneth M.
Published: March 2005

In the Realm of the Diamond Queen: MarginalIty In an Out‐of‐the‐Way Place. ANNA LOWENHAUPT TSING. Princeton, NJ: Princeton University Press, 1993. xvi + 350 pp., photographs, notes, references, index.
Wedding bell blues: Marriage, missing men, and matrifocal follies
Authors: Blackwood Evelyn
Published: March 2005

In this article, I revisit debates about so‐called matrifocal societies as a way to critique the centrality of heteronormative marriage and family in anthropology. Using gender as a tool of analysis, I argue that anthropologists have relied on the trope of the dominant heterosexual man, what I call the “Patriarchal Man,” to create and sustain concepts of “marriage” and “family.” By examining the discourse on matrifocality in studies of Afro‐Caribbean and Minangkabau households, I show how it is the “missing man,” the dominant heterosexual man, who is the key to the construction and perpetuation of the matrifocal concept and, by extension, the motor of marriage, family, and kinship. This fixity on the dominant heterosexual man has led anthropologists to misrecognize other forms of relatedness as less than or weaker than heteronormative marriage. I suggest that, rather than positing a foundational model for human sociality, intimacy, or relatedness, researchers look for webs of meaningful relationships in their historical and social specificity.
Cobo and tabua in Fiji: Two forms of cultural currency in an economy of sentiment
Authors: Arno Andrew
Published: March 2005

Cultural currency, defined in performance terms, is a highly specific medium for the deployment of sentiment in community life, and it can be usefully compared with varieties of material currency. Sentiment, as a cultural system, is an intellectual rather than a material property, and, like all property, it is defined by social relationships and obligations. Cultural currencies are performances that are constrained in use by meaning and identity, rather than by physical possession. Research on the cobo and tabua in Fiji represents an ethnographic case study of cultural currency that has implications for investigating the relationships among culture, sentiment, property, and mode of production generally.
The Apotheosis of Josquin des Prez and Other Mythologies of Musical Genius
Authors: Higgins Paula
Published: March 2005

Within the theoretical framework of Roland Barthes's writings on myth and ideology, this essay seeks to expose the historical legitimation project through which the mythmaking, universalizing rhetoric of musical genius that has long surrounded the figure of Ludwig van Beethoven came to infiltrate scholarship on Josquin des Prez, culminating in his late twentieth-century apotheosis. Contextualizing the composer's reception history with respect to the debates between Joseph Kerman and Edward Lowinsky in 1965 and especially the 1971 Josquin Festival-Conference, the author suggests that the ideological refashioning of Josquin in the image of Beethoven has simultaneously shaped and derailed the intellectual trajectory of early music scholarship in the past thirty years. By privileging a discourse of musical genius in the service of which, among other concerns, the canon of works attributed to the composer is being decimated beyond historical recognition, the richness and complexity of the musical culture of which he was a vital part risks being overshadowed and obfuscated by the disproportionate amount of attention invested in his singular accomplishments. The essay advocates a resolute historicization of sixteenth-century discourses of creative endowment, a critical reassessment of the role of authentication scholarship in Josquin studies, and a renewed sensitivity to the imbrication of mythologies of musical genius in music historiographies of both the past and the present.
Images of Telemann: Narratives of Reception in the Composer's Anecdote, 1750-1830
Authors: Zohn Steven
Published: March 2005

Studies of musical Rezeptionsgeschichte tend to construct and privilege an "official" history based largely upon the writings of scholars, critics, and lexicographers-sources full of authoritative opinions and verifiable facts. Often devalued in this process are "unofficial," unverifiable, and apparently less serious sources such as published anecdotes, which may in fact have no less to tell us about how posterity viewed a given composer. The posthumous reputation of Georg Philipp Telemann is a case in point. Almost universally revered during his lifetime but gradually reduced to the stature of a large Kleinmeister by late 18th- and early 19th-century critics and scholars, Telemann is featured in a number of anecdotes published between 1776 and 1830. These stories, some of which owe their origin to Telemann himself, reveal a more variegated picture of the man and his music than that crafted in contemporaneous intellectual circles. Aside from portraying Telemann as a sharp-witted musician who "thought quickly and beautifully," they illuminate several anecdotal archetypes and biographical tropes that served to demystify the nature of genius for musical Liebhaber, the main consumers of such tales.
Plagal Harmony as Other: Asymmetrical Dualism and Instrumental Music by Brahms
Authors: Notley Margaret
Published: March 2005

The late 19th-century dualism of Hugo Riemann exemplifies a widely recognized tendency in Western cultures to think in binary pairs. In recent theoretical writing the primary dualism between major and minor modes has provoked little or no controversy. But the attendant opposition between, respectively, authentic and plagal harmonic systems has not found widespread acceptance, because theorists have been unwilling to grant the latter equal status to the former. An alternative is to accept the validity of the two systems and at the same time to recognize the inequality that comes with any binary pair, thus acknowledging the "otherness" or, to borrow a term from linguistics, the "markedness" of the plagal system. In an essay from 1889, Riemann explored striking harmonic effects in the Andante of the Fourth Symphony and another late orchestral movement by Brahms, discerning the same non-diatonic scale behind the (plagal) idioms in both. The Phrygian and Aeolian scales enable similar unusual plagal passages in two chamber movements by Brahms, the early Adagio mesto of the Horn Trio and the very late opening Allegro from the Clarinet Trio. In these movements plagal harmony appears in a strong sense as the other of authentic harmony and perhaps even of common-practice tonality itself. The semantic significance of certain plagal moments in both has to do above all with their ability to suggest something other than, outside of, or prior to tonal music.
Expression profiling of androgen-dependent and -independent LNCaP cells: EGF versus androgen signalling
Authors: Oosterhoff Josien K , Grootegoed J Anton , Blok Leen J
Published: March 2005

Prostate cancer development often includes a shift from androgen-dependent to androgen-independent growth. It is hypothesized that, during this transition, growth factors like the epidermal growth factor (EGF) gain importance as activators of tumour cell proliferation. To study this, androgen- and EGF-regulation of growth and gene-expression was analysed in the androgen-dependent human prostate cancer cell line LNCaP-FGC (FGC) and its androgen-independent derivative line LNCaP-LNO (LNO). It was observed that androgen-dependent FGC cells require exposure to either androgens or EGF to proliferate. This is in contrast to androgen-independent LNO cells that showed significant proliferation in medium depleted of androgens and growth factors. Gene expression data were obtained for the androgen-dependent FGC and androgen-independent LNO cells cultured in the presence or absence of androgens (synthetic R1881) or EGF for different time periods. Expression profiling showed that many cell cycle genes, including a number of androgen- and EGF-regulated genes, are constitutively activated in androgen-independent LNO cells. Furthermore, the overlap between changes in gene expression activated by androgen and EGF receptor signalling pathways was found to be very high (75%). These results partly explain why androgen-independent LNO cells can proliferate in the absence of androgenic stimulation. However, possibly other, so far unknown, signal transduction pathways that induce and maintain proliferation, have also been activated.
Recent Developments in the Field of Tumor-Inhibiting Metal Complexes
Authors: Galanski M. S. , Arion V. B. , Jakupec M. A. , Keppler B. K.
Published: March 2005

25 years after the first approval of cisplatin in the clinic against a number of cancer diseases, cisplatin and related compounds continue to be among the most efficient anticancer drugs used so far. Efforts are focused to develop novel platinum- and non-platinum-based antitumor drugs to improve clinical effectiveness, to reduce general toxicity and to broaden the spectrum of activity. In the field of non-platinum compounds exhibiting anticancer properties, ruthenium complexes are very promising, showing activity on tumors which developed resistance to cisplatin or in which cisplatin is inactive. Furthermore, general toxicity was found to be very low. The first ruthenium compound NAMI-A entered phase I clinical trials in 1999 as an antimetastatic drug, whereas the ruthenium complex KP1019 will enter phase I clinical trials in 2003 as an anticancer drug which is among others very active against colon carcinomas and their metastases. Remarkable progress is also seen in developing tumor inhibiting gallium compounds. One of them, KP46, will also enter phase I clinical trials in 2003. This article reviews briefly the achievements in the field of anticancer metal complexes focusing the discussion onto the impact of the group of Bioinorganic Chemistry at the Department of Inorganic Chemistry at the University of Vienna. The development of pH sensitive platinum prodrugs, platinum-based drug targeting strategies with low-molecular-weight carriers, kinetically inert platinum(IV) complexes, as well as tumor inhibiting non-platinum anticancer drugs based on ruthenium and gallium is covered in the following sections.