bluuebunny/crossref_metadata_2025 huggingface dataset:
Chronic exposure to fulvestrant promotes overexpression of the c-Met receptor in breast cancer cells: implications for tumour–stroma interactions
Authors: Hiscox Stephen , Jordan Nicola J , Jiang Wen , Harper Maureen , McClelland Richard , Smith Chris , Nicholson Robert I
Published: December 2006

Our previous investigations using cell models of tamoxifen resistance have shown that the acquisition of an endocrine-insensitive state is accompanied by an invasive in vitro phenotype. In this study, we wished to determine whether this was specifically related to partial oestrogen receptor agonists or whether similar phenomena arise with the newer ‘pure’ anti-oestrogens, exemplified by fulvestrant. Our data demonstrate that the development of fulvestrant resistance in two breast cancer cell lines, MCF7 and T47D, is accompanied by an augmented migratory and invasive phenotype in vitro and overexpression of the HGF/SF receptor, c-Met. Importantly, upregulated c-Met expression in these cells facilitates their stimulation by HGF/SF-secreting stromal fibroblasts, leading to the activation of Src, Akt and ERK1/2 and a profound enhancement of their aggressive phenotype in vitro. These effects could be specifically attributable to activation of the c-Met receptor since the inclusion of neutralising antibodies to c-Met, or siRNA-mediated knockdown of c-Met expression, suppressed both invasion and migration stimulated by either exogenous HGF/SF, fibroblast-conditioned medium or following co-culture with fibroblast cells. Together, these in vitro data suggest that the development of fulvestrant resistance in vivo may confer a metastatic advantage to the cells by allowing their migratory and invasive behaviour to be augmented by surrounding stromal cells.
Calcium-dependent growth regulation of small cell lung cancer cells by neuropeptides
Authors: Gudermann Thomas , Roelle Susanne
Published: December 2006

Approximately 15–25% of all primary cancers of the lung are classified histologically as small cell lung carcinoma (SCLC), a subtype characterized by rapid growth and a poor prognosis. Neuropeptide hormones like bombesin/gastrin-releasing peptide, bradykinin or galanin are the principal mitogenic stimuli of this tumour entity. The mitogenic signal is transmitted into the cell via heptahelical neuropeptide hormone receptors, which couple to the heterotrimeric G proteins of the Gq/11 familiy. Subsequent activation of phospholipase Cβ (PLCβ) entails the activation of protein kinase C and the elevation of the intracellular calcium concentration. There is mounting evidence to support the notion that calcium mobilization is the key event that initiates different mitogen-activated protein kinase cascades. Neuropeptide-dependent proliferation of SCLC cells relies on parallel activation of the Gq/11/PLCβ/Ras/extracellular signal-regulated kinase and the c-jun N-terminal kinase pathways, while selective engagement of either signalling cascade alone results in growth arrest and differentiation or apoptotic cell death. Basic experimental research has the potential to identify and validate novel therapeutic targets located at critical points of convergence of different mitogenic signal transduction pathways. In the case of SCLC, targeting the distinct components of the Ca2+ influx pathway as well as critical Ca2+-dependent cellular effectors may be rewarding in this regard.
Beyond Seat Time and Student Satisfaction: A Curricular Approach to Residential Education
Authors: Kerr Kathleen G. , Tweedy James
Published: December 2006

The success of a traditional residential education program is typically measured by numbers of students who attend and how much they liked it. Kathleen Kerr and James Tweedy offer a peer-reviewed curricular approach that determines success by how much students learn.
R U Signed On?
Authors: Martin Jodi Koslow
Published: December 2006

Joining students’ 24/7 instant messaging world sends dread through many an educator. Jodi Koslow Martin of Aurora University, by contrast, believes that being an easily accessible icon on her students’ computer screens is an important part of her work.
National Issues Forums
Authors: Parkins Leslie
Published: December 2006

Practicing democracy on campus
Difficult dilemmas: The meaning and dynamics of being out in the classroom
Authors: Bettinger Thomas V. , Timmins Rebecca , Tisdell Elizabeth J.
Published: December 2006

This chapter explores the dilemmas and perceptions of being open regarding nonheterosexual sexual orientations in the higher education classroom from the individual perspectives of the three coauthors.
LGBTQ issues in organizational settings: What HRD professionals need to know and do
Authors: Muñoz Corey S. , Thomas Kecia M.
Published: December 2006

This chapter outlines the unique experiences of gay and lesbians in organizational settings and offers best practices for human resource professionals in supporting their sexual minority employees.
Tuning the β‐turn segment in designed peptide β‐hairpins: Construction of a stable type I′ β‐turn nucleus and hairpin–helix transition promoting segments
Authors: Rai Rajkishor , Raghothama Srinivasarao , Sridharan Rajagopalan , Balaram Padmanabhan
Published: December 2006

Designed octapeptides Boc‐Leu‐Val‐Val‐Aib‐DXxx‐Leu‐Val‐Val‐OMe (DXxx = DAla, 3a;DVal, 3c and DPro, 5a) and Boc‐Leu‐Phe‐Val‐Aib‐DAla‐Leu‐Phe‐Val‐OMe (3b) have been investigated to construct models of a stable type I′ β‐turn nucleated hairpin and to generate systems for investigating helix–hairpin conformational transitions. Peptide 5a, which contains a central Aib‐DPro segment, is shown to adopt a stable type I′ β‐turn nucleated hairpin structure, stabilized by four cross‐strand hydrogen bonds. The stability of the structure in diverse solvents is established by the observation of all diagnostic NOEs expected in a β‐hairpin conformation. Replacement of DPro5 by DAla/DVal (3a–c) results in sequences that form β‐hairpins in hydrogen bonding solvents like CD3OH and DMSO‐d6. However, in CDCl3 evidence for population of helical conformations is obtained. Peptide 6b (Boc‐Leu‐Phe‐Val‐Aib‐Aib‐Leu‐Phe‐Val‐OMe), which contains a centrally positioned Aib‐Aib segment, provides a clear example of a system, which exhibits a helical conformation in CDCl3 and a significant population of both helices and hairpins in CD3OH and DMSO‐d6. The coexistence of multiple conformations is established by the simultaneous observation of diagnostic NOEs. Control over stereochemistry of the central β‐turn permits generation of models for robust β‐hairpins and also for the construction of systems that may be used to probe helix–hairpin conformational transitions. © 2006 Wiley Periodicals, Inc. Biopolymers (Pept Sci) 88: 350–361, 2007.

This article was originally published online as an accepted preprint. The “Published Online” date corresponds to the preprint version. You can request a copy of the preprint by emailing the Biopolymers editorial office at biopolymers@wiley.com
NMR studies of dynamics in RNA and DNA by 13C relaxation
Authors: Shajani Zahra , Varani Gabriele
Published: December 2006

RNA and DNA molecules experience motions on a wide range of time scales, ranging from rapid localized motions to much slower collective motions of entire helical domains. The many functions of RNA in biology very often require this molecule to change its conformation in response to biological signals in the form of small molecules, proteins or other nucleic acids, whereas local motions in DNA may facilitate protein recognition and allow enzymes acting on DNA to access functional groups on the bases that would otherwise be buried in Watson‐Crick base pairs. Although these statements make a compelling case to study the sequence dependent dynamics in nucleic acids, there are few residue‐specific studies of nucleic acid dynamics. Fortunately, NMR studies of dynamics of nucleic acids and nucleic acids‐protein complexes are gaining increased attention. The aim of this review is to provide an update of the recent progress in studies of nucleic acid dynamics by NMR based on the application of solution relaxation techniques. © 2006 Wiley Periodicals, Inc. Biopolymers 86: 348–359, 2007.

This article was originally published online as an accepted preprint. The “Published Online” date corresponds to the preprint version. You can request a copy of the preprint by emailing the Biopolymers editorial office at biopolymers@wiley.com
Bifunctional Ligands that Target Cells Displaying the αvβ3 Integrin
Authors: Owen Robert M. , Carlson Coby B. , Xu Jinwang , Mowery Patricia , Fasella Elisabetta , Kiessling Laura L.
Published: December 2006

Strategies to eliminate tumor cells have long been sought. We envisioned that a small molecule could be used to decorate the offending cells with immunogenic carbohydrates and evoke an immune response. To this end, we describe the synthesis of bifunctional ligands possessing two functional motifs: one binds a cell‐surface protein and the other binds a naturally occurring human antibody. Our conjugates combine an RGD‐based peptidomimetic, to target cells displaying the αvβ3 integrin, with the carbohydrate antigen galactosyl‐α(1–3)galactose [Galα(1–3)Gal or α‐Gal]. To generate such bifunctional ligands, we designed and synthesized RGD mimetics 1 b and 2 c, which possess a free amino group for modification. These compounds were used to generate bifunctional derivatives 1 c and 2 d, with dimethyl squarate serving as the linchpin; thus, our synthetic approach is modular. To evaluate the binding of our peptidomimetics to the target αvβ3‐displaying cells, we implemented a cell‐adhesion assay. Results from this assay indicate that the designed, small‐molecule ligands inhibit αvβ3‐dependent cell adhesion. Additionally, our most effective bifunctional ligand exhibits a high degree of selectivity (4000‐fold) for αvβ3 over the related αvβ5 integrin, a result that augurs its utility in specific cell targeting. Finally, we demonstrate that the bifunctional ligands can bind to αvβ3‐positive cells and recruit human anti‐Gal antibodies. These results indicate that both the integrin‐binding and the anti‐Gal‐binding moieties can act simultaneously. Bifunctional conjugates of this type can facilitate the development of new methods for targeting cancer cells by exploiting endogenous antibodies. We anticipate that our modifiable αvβ3‐binding ligands will be valuable in a variety of applications, including drug delivery and tumor targeting.
Caged Capsaicins: New Tools for the Examination of TRPV1 Channels in Somatosensory Neurons
Authors: Gilbert Daniel , Funk Katharina , Dekowski Brigitte , Lechler Ralf , Keller Sandro , Möhrlen Frank , Frings Stephan , Hagen Volker
Published: December 2006

The vanilloid capsaicin,N‐(4‐hydroxy‐3‐methoxybenzyl)‐8‐methylnon‐6‐enamide, is the pungent ingredient of chili peppers and is used in pain research as an activating ligand of heat‐sensitive transduction channels in nociceptive neurons. Here we describe the synthesis and application of two capsaicin derivatives modified at the hydroxy function of the vanillyl motif: α‐carboxy‐4,5‐dimethoxy‐2‐nitrobenzyl‐caged (CDMNB‐caged) capsaicin and {7‐[bis(carboxymethyl)amino]coumarin‐4‐yl}methoxycarbonyl‐caged (BCMACMOC‐caged) capsaicin. These compounds show dramatically reduced pungency, but release active capsaicin upon irradiation with UV light. CDMNB‐caged capsaicin can be used to perform concentration‐jump experiments, while BCMACMOC‐caged capsaicin is membrane‐impermeant and can be applied selectively to the intracellular or extracellular sides of a plasma membrane. Both compounds can serve as valuable research tools in pain physiology.
8‐Hydroxy‐2′‐deoxyguanosine (8‐OH‐dG) as a potential survival biomarker in patients with nonsmall‐cell lung cancer
Authors: Shen Jie , Deininger Prescott , Hunt Jay D. , Zhao Hua
Published: December 2006

BACKGROUND.

8‐Hydroxy‐2′‐deoxyguanosine (8‐OH‐dG) is 1 of the most abundant oxidative products of cellular DNA. Accumulation of impaired 8‐OH‐dG could lead to increased genomic instability that in turn could lead to a more malignant phenotypic behavior of tumors. Therefore, the effects of 8‐OH‐dG on survival in 99 resected nonsmall‐cell lung cancer (NSCLC) patients was evaluated.

METHODS.

The enzyme‐linked immunosorbent assay was applied to measure the levels of 8‐OH‐dG in tumor DNA. The median levels of 8‐OH‐dG were 6.5 pmol/μg for all study subjects.

RESULTS.

Patients with low levels of 8‐OH‐dG had significantly longer survival times compared with those with high levels of 8‐OH‐dG (log‐rank test: P < .001). In Cox regression analysis, patients with high levels of 8‐OH‐dG had an over 3‐fold increased hazard of death. In addition, a statistically significant correlation between levels of 8‐OH‐dG and age was noted (rho = 0.206, P = .048). Furthermore, we observed a genotype‐phenotype modification between hOGG1 gene polymorphism (Ser326Cys) and levels of 8‐OH‐dG.

CONCLUSIONS.

The results demonstrated that levels of 8‐OH‐dG could predict survival in resected NSCLC patients. It is postulated that an intact base excision repair mechanism may reduce the accumulation of oxidative DNA damage that is thought to contribute to the tumor's malignant potential and therefore the risk of death. Cancer 2007 © 2006 American Cancer Society.
Neuropeptide Y activates urocortin 1 neurons in the nonpreganglionic Edinger‐Westphal nucleus
Authors: Gaszner Balázs , Korosi Anikó , Palkovits Miklós , Roubos Eric W. , Kozicz Tamás
Published: December 2006

Central regulatory pathways promoting stress adaptation utilize various neurotransmitters/neuropeptides, such as urocortin 1 (Ucn1) and neuropeptide Y (NPY). Ucn1 is abundantly expressed in the nonpreganglionic Edinger‐Westphal nucleus (npEW), where it is codistributed with NPY‐immunoreactive (ir) terminals. A special role for both neuropeptides has been postulated in stress adaptation. Using double‐labeling immunohistochemistry, we observed close appositions between NPY‐ir terminals and neurons immunoreactive for Ucn1 in the rat, as well as in the human npEW. Therefore, we hypothesized that NPY might control the activity of Ucn1‐positive neurons in the npEW. To test this hypothesis, NPY was injected into the lateral cerebral ventricle of rats, resulting in a strong activation of npEW Ucn1 neurons as revealed by Fos immunohistochemistry. Ucn1 mRNA was also upregulated in the npEW 2 hours after the injection of NPY. In a search for the type of NPY receptor that mediates this NPY‐induced recruitment of npEW‐Ucn1 cells, we found that the great majority of Ucn1 cells exhibited NPY Y5 receptor immunoreactivity, and only a few of the Ucn1 cells coexpressed the Y1 receptor. We concluded that NPY, via NPY Y5 and to a lesser extent via the Y1 receptors, exerts a stimulatory action on Ucn1 cells in the npEW. Further studies are currently in progress to elucidate the significance of this NPY–Ucn1 interaction in the npEW. J. Comp. Neurol. 500:708–719, 2007. © 2006 Wiley‐Liss, Inc.
Anatomical organization of antennal lobe projection neurons in the moth Heliothis virescens
Authors: RØ Helge , Müller Dirk , Mustaparta Hanna
Published: December 2006

A prerequisite for understanding how odor information is coded in the central nervous system is to know the morphology and spatial relationship of the principal neurons forming the olfactory pathways. The present account provides an anatomical description of the morphology of the neuronal connections between the antennal lobe and the protocerebrum in the moth Heliothis virescens, a species used for studies of olfactory processing and learning. Intracellular labeling and antennal lobe focal injections with dextran fluorescent markers were combined with neuropil immunostaining and three‐dimensional reconstructions. The experiments revealed four antennocerebral tracts, the inner, middle, outer, and dorsomedial, and eight morphological types of projection neurons in addition to a neuron with an unpaired median soma in the subesophageal ganglion. Multiglomerular projection neurons, present in all but the dorsomedial antennocerebral tract, project in several olfactory foci of the protocerebral neuropil. With few exceptions, these neurons do not innervate the calyces of the mushroom body. Uniglomerular projection neurons appear most numerous in the inner antennocerebral tract but are also present in the outer and dorsomedial tracts. These neurons always ramify in the calyces of the mushroom body and in the lateral horn. The projection areas of the neurons following different tracts are largely separated in the secondary olfactory centers. This is most evident in the lateral horn, whereas, in the calyces, the axonal ramifications are more intermingled. The mushroom body architecture, revealed by neuropil immunolabeling, showed striking similarities to that of other lepidopteran species as well as insects of other taxa. J. Comp. Neurol. 500:658–675, 2007. © 2006 Wiley‐Liss, Inc.
Axonal bias at a representational border in adult rat somatosensory cortex (S1)
Authors: Steen Patricia A. , Mason Matthew , Pham Lanchi , Lefebvre Yann , Hickmott Peter W.
Published: December 2006

The cortex is a highly organized structure and this organization is integral to cortical function. However, the circuitry underlying cortical organization is only partially understood, thus limiting our understanding of cortical function. Within the somatosensory cortex, organization is manifest as a map of the body surface. At the level of the cortical circuitry the horizontal connections of Layer 2/3 express a physiological bias that reflects discontinuities within the somatosensory map. Both excitation and inhibition are smaller when evoked from across a representational border, as compared to when they are evoked from within the representation. This physiological bias may be due to a bias in either the strength or number of synapses and/or the number of axons that cross this border and the extent of their arborization. In this study we used both an anterograde (Phaseolus vulgaris leucoagglutinin) and a retrograde (cholera toxin B) tracer to examine Layer 2/3 horizontal projections in rat S1. We determined that there is a bias in the amount of horizontal axonal projections that cross the forepaw/lower jaw border as compared to projections remaining within an individual representation. This bias in axonal projection and the correlated bias in excitation and inhibition may underlie the expression of the representational border. J. Comp. Neurol. 500:634–645, 2007. © 2006 Wiley‐Liss, Inc.
Premotor circuits controlling eyelid movements in conjunction with vertical saccades in the cat: II. Interstitial nucleus of Cajal
Authors: Chen Bingzhong , May Paul J.
Published: December 2006

Vertical saccadic eye movements are accompanied by concurrent eyelid movements in the same direction. The interstitial nucleus of Cajal (InC) controls eye position for vertical eye movements and may also control saccade‐related lid position as well. This study investigates whether the InC serves as a premotor center for eyelid saccades, by employing dual‐tracer methods in cats to label both the projections of the InC and the motoneurons supplying the levator palpebrae superioris (LPS) muscle, which lie in the caudal central subdivision (CCS) of the oculomotor complex. Injections of biotinylated dextran amine (BDA) into the InC anterogradely labeled axons that terminated bilaterally throughout the CCS and in the oculomotor nuclei proper. Labeled terminals lay in close association with labeled LPS motoneurons, which were retrogradely labeled following injections of wheat germ agglutinin‐conjugated horseradish peroxidase (WGA‐HRP) into the muscle. Ultrastructural investigation revealed that most terminals contained spherical vesicles and formed asymmetric synaptic contacts with the labeled motoneurons. These results strongly suggest that the InC monosynaptically controls lid movements in conjunction with vertical eye movements, including saccades. To identify the neurons of origin for this pathway, WGA‐HRP injections were centered in the CCS. These experiments indicate that lid and eye motoneurons may share a common source of bilateral InC input. Thus, a common vertical position signal may be employed to maintain the lid and eye at appropriate elevations during fixation, such that the lid sits just above the pupil, allowing unobstructed vision, but at the ready to protect the cornea. J. Comp. Neurol. 500:676–692, 2007. © 2006 Wiley‐Liss, Inc.
Distribution of soluble guanylyl cyclase in rat retina
Authors: Ding Jin‐Dong , Weinberg Richard J.
Published: December 2006

The nitric oxide (NO)‐cGMP pathway is implicated in modulation of visual information processing in the retina. Despite numerous functional studies of this pathway, information about the retinal distribution of the major downstream effector of NO, soluble guanylyl cyclase (sGC), is very limited. In the present work, we have used immunohistochemistry and multiple labeling to determine the distribution of sGC in rat retina. sGC was present at high levels in inner retina but barely detectable in outer retina. Photoreceptors and horizontal cells, as well as Müller cells, were immunonegative, whereas retinal ganglion cells exhibited moderate staining for sGC. Strong immunostaining was found in subpopulations of bipolar and amacrine cells, but staining was weak in rod bipolar cells, and AII amacrine cells were immunonegative. Double labeling of sGC with neuronal nitric oxide synthase showed that the two proteins are generally located in adjacent puncta in inner plexiform layer, implying paracrine interactions. Our results suggest that the NO‐cGMP pathway modulates the neural circuitry in inner retina, preferentially within the cone pathway. J. Comp. Neurol. 500:734–745, 2007. © 2006 Wiley‐Liss, Inc.
Vessicular glutamate transporters 1 and 2 are differentially associated with auditory nerve and spinal trigeminal inputs to the cochlear nucleus
Authors: Zhou Jianxun , Nannapaneni Naveen , Shore Susan
Published: December 2006

Projections of glutamatergic somatosensory and auditory fibers to the cochlear nucleus (CN) are mostly nonoverlapping: projections from the spinal trigeminal nucleus (Sp5) terminate primarily in the granule cell domains (GCD) of CN, whereas type I auditory nerve fibers (ANFs) project to the magnocellular areas of the VCN (VCNm) and deep layers of Dorsal CN (DCN). Vesicular glutamate transporters (VGLUTs), which selectively package glutamate into synaptic vesicles, have different isoforms associated with distinct subtypes of excitatory glutamatergic neurons. Here we examined the distributions of VGLUT1 and VGLU2 expression in the CN and their colocalization with Sp5 and ANF terminals following injections of anterograde tracers into Sp5 and the cochlea in the guinea pig. The CN regions that showed the most intense expression of VGLUT1 and VGLUT2 were largely nonoverlapping and were consistent with ANF and Sp5 projections, respectively: VGLUT1 was highly expressed in VCNm and the molecular layer of the DCN, whereas VGLUT2 was expressed predominantly in the GCD. Half (47% ± 3%) of the Sp5 mossy fiber endings colabeled with VGLUT2, but few (2.5% ± 1%) colabeled with VGLUT1. In contrast, ANFs colabeled predominantly with VGLUT1. The pathway‐specific expression of VGLUT isoforms in the CN may be associated with the intrinsic synaptic properties that are unique to each sensory pathway. J. Comp. Neurol. 500:777–787, 2007. © 2006 Wiley‐Liss, Inc.
Taste‐evoked Fos expression in nitrergic neurons in the nucleus of the solitary tract and reticular formation of the rat
Authors: Travers Susan P. , Travers Joseph B.
Published: December 2006

The current investigation used double labeling for NADPHd and Fos‐like immunoreactivity to define the relationship between nitric oxide synthase‐containing neural elements and taste‐activated neurons in the nucleus of the solitary tract (NST) and subjacent reticular formation (RF). Stimulation of awake rats with citric acid and quinine resulted in significant increases in the numbers of double‐labeled neurons in both the NST and RF, suggesting that some medullary gustatory neurons utilize nitric oxide (NO) as a transmitter. Overall, double‐labeled neurons were most numerous in the caudal reaches of the gustatory zone of the NST, where taste neurons receive inputs from the IXth nerve, suggesting a preferential role for NO neurons in processing gustatory inputs from the posterior oral cavity. However, double‐labeled neurons also exhibited a preferential distribution depending on the gustatory stimulus. In the NST, double‐labeled neurons were most numerous in the rostral central subnucleus after either stimulus but had a medial bias after quinine stimulation. In the RF, after citric acid stimulation, there was a cluster of double‐labeled neurons with distinctive large soma in the parvicellular division of the lateral RF, subjacent to the rostral tip of NST. In contrast, in response to quinine, there was a cluster of double‐labeled neurons with much smaller soma in the intermediate zone of the medial RF, a few hundred micrometers caudal to the citric acid cluster. These differential distributions of double‐labeled neurons in the NST and RF suggest a role for NO in stimulus‐specific gustatory autonomic and oromotor reflex circuits. J. Comp. Neurol. 500:746–760, 2007. © 2006 Wiley‐Liss, Inc.
Comparative analysis of the subcellular and subsynaptic localization of mGluR1a and mGluR5 metabotropic glutamate receptors in the shell and core of the nucleus accumbens in rat and monkey
Authors: Mitrano Darlene A. , Smith Yoland
Published: December 2006

Group I metabotropic glutamate receptors (mGluRs) play critical roles in synaptic plasticity and drug addiction. To characterize potential sites whereby these receptors mediate their effects in the ventral striatum, we studied the subcellular and subsynaptic localization of mGluR1a and mGluR5 in the shell and core of the nucleus accumbens in rat and monkey. In both species, group I mGluRs are mainly postsynaptic in dendrites and spines, with rare presynaptic labeling in unmyelinated axons. Minor, yet significant, differences in proportions of specific immunoreactive elements were found between the accumbens shell and the accumbens core in monkey. At the subsynaptic level, significant differences were found in the proportion of plasma membrane‐bound mGluR5 labeling between species. In dendrites, spines, and unmyelinated axons, a significantly larger proportion of mGluR5 labeling was bound to the plasma membrane in rats (50–70%) than in monkeys (30–50%). Conversely, mGluR1a displayed the same pattern of immunogold labeling in the two species. Electron microscopic colocalization studies revealed 30% colocalization of mGluR1a and mGluR5 in dendrites and as much as 50–65% in spines in both compartments of the rat accumbens. Both group I mGluRs were significantly expressed in D1‐immunoreactive dendritic processes (60–75% colocalization) and spines (30–50%) of striatal projection neurons as well as dendrites of cholinergic (30–70%) and parvalbumin‐containing (70–85%) interneurons. These findings highlight the widespread expression of group I mGluRs in projection neurons and interneurons of the shell and core of the nucleus accumbens, providing a solid foundation for regulatory and therapeutic functions of group I mGluRs in reward‐related behaviors and drug addiction. J. Comp. Neurol. 500:788–806, 2007. © 2006 Wiley‐Liss, Inc.
Asymmetric effects of dynamic usage behavior on duration in subscription-based online service
Authors: Dover Howard F. , Murthi B.P.S.
Published: December 2006

In this article, we develop a model to predict the lifetime duration of customers for a subscription-based online content provider. In contrast to prior research, this article employs a dynamic measure of usage and compares alternate model specifications. A proportional hazard model is used with time-varying usage covariates obtained from Web logs while controlling for initial purchase characteristics such as purchase price and billing frequency. We test and find evidence for violation of the proportionality assumption in the hazard model and conclude that a stratified hazard model provides the best model fit. The results show that customers who are billed monthly for annual subscriptions maintain their subscriptions longer than do customers billed quarterly, when compared to annual subscriptions. Furthermore, dynamic changes in usage have an asymmetric effect on duration, with increases in usage having a stronger effect than do decreases in usage. Managers can use this model to identify the customers to be targeted for both retention and upgrade.
A dynamic segmentation approach for targeting and customizing direct marketing campaigns
Authors: Reutterer Thomas , Mild Andreas , Natter Martin , Taudes Alfred
Published: December 2006

An important aspect of customer relationship management is the targeting of customer segments with tailored promotional activities. While most contributions focus on the selection of promising customers for targeting, only few authors address the question of which specific differential offers to direct to the selected target groups. We focus on both issues and propose a flexible, two-stage approach for dynamically deriving behaviorally persistent segments and subsequent target marketing selection using retail-purchase histories from loyalty-program members. The underlying concept of behavioral persistence entails an in-depth analysis of complementary cross-category purchase interdependencies at a segment level. The effectiveness and efficiency of the proposed procedure are demonstrated in a controlled field experiment involving the targeting of several thousands of customers enrolled in the loyalty program of a “do-it-yourself” retailer. Our empirical findings provide evidence of significant positive impacts on both profitability and sales for segment-specific tailored direct marketing campaigns.
FTY720 enhances the activation‐induced apoptosis of donor T cells and modulates graft‐versus‐host disease
Authors: Hashimoto Daigo , Asakura Shoji , Matsuoka Ken‐ichi , Sakoda Yukimi , Koyama Motoko , Aoyama Kazutoshi , Tanimoto Mitsune , Teshima Takanori
Published: December 2006

FTY720 is a novel immunosuppressant that improves the outcomes after solid organ and bone marrow transplantation (BMT) due to the sequestration of T cells into LN. We tested the hypothesis that the sequestration of donor T cells in LN by FTY720 would enhance their interaction with host APC, thus causing a greater degree of activation‐induced apoptosis of alloreactive T cells, and thereby resulting in a reduction of graft‐vs.‐host disease (GVHD). The short‐term administration of FTY720 improved the recipient survival after allogeneic BMT. FTY720 treatment facilitated a rapid contraction of the donor T cell pool in association with an increased degree of apoptosis of donor T cells. The donor T cell reactivity to host alloantigens was diminished in host's LN and adoptive transfer of donor T cells isolated from LN of FTY720‐treated recipients of allogeneic BMT induced less severe GVHD in secondary recipients than the transfer from controls. Caspase‐dependent apoptosis was involved in this mechanism because FTY720‐induced protection was abrogated when a pan‐caspase inhibitor was administered. These findings thus demonstrate the presence of a novel mechanism by which FTY720 modulates the allogeneic T cell responses: namely, by the induction of activation‐induced apoptosis of alloreactive T cells in LN.
Mast cell‐expressed complement receptor, not TLR2, is the main detector of zymosan in peritonitis
Authors: Mullaly Sarah C. , Kubes Paul
Published: December 2006

The in vitro macrophage response to zymosan has been attributed to Toll‐like receptor 2 (TLR2). Whether TLR2 is obligatory for the zymosan‐induced in vivo response has not been assessed. The importance of this question is underscored by the fact that zymosan activates complement in a cell‐independent manner. We have investigated whether the in vitro observation of TLR2 as the dominant zymosan receptor on macrophages would translate to an experimental peritonitis model in vivo. We have treated mice with zymosan, resulting in significant leukocyte (primarily neutrophil) accumulation in the peritoneum at 4 h. Zymosan‐mediated leukocyte recruitment was TLR2 independent, but was predominantly dependent on the complement components, C3 and C5a with a minor contribution from LTB4. Peritoneal neutrophilia was 50% mast cell dependent and this defect was reproduced using C5a receptor (C5aR)‐deficient mast cells in mast cell‐deficient mice, suggesting that C5aR is responsible for mast cell activation following zymosan challenge. By 24 h, the response to zymosan involved primarily monocyte recruitment and was C3 and C5aR independent. Taken together, these studies indicate that the in vivo inflammatory response to zymosan does not necessarily mimic the TLR2 dependence observed in vitro, and that complement plays a dominant role in early, but not late, zymosan‐mediated peritonitis.
The role of mineralogy, geochemistry and grain size in badland development in Pisticci (Basilicata, southern Italy)
Authors: Summa V. , Tateo F. , Medici L. , Giannossi M. L.
Published: December 2006

Mineralogical, geochemical and grain‐size composition of soil and pore‐water chemistry parameters were characterized on both eroded (south‐facing) and non‐eroded (north‐facing) clayey‐silt slopes in the Basilicata region (southern Italy).

Only a few grain‐size parameters and clay mineralogy discriminate eroded from non‐eroded substrates. Compared with the latter, the former have fractions of over 63 µm and 1–4 µm lower and fractions 4–63 µm higher. Grain‐size characters of crusts did not discriminate with respect to substrate.

Bulk rock mineralogy was not distinctive, but the clay mineral assemblage shows that the eroded slope is enriched in kaolinite, mixed layers (illite–smectite) and chlorite, whereas illite decreases, although overlaps are common.

Chemical data enable discrimination between eroded and non‐eroded slopes. pH, SAR (sodium adsorption ratio), TDS (total dissolved salts) and PS (percentage of sodium) are distinctive parameters for both eroded and non‐eroded slopes. TDS increases in depth in the non‐eroded slope, whereas the maximum TDS is just below the crust in the eroded one. On average, eroded substrates are higher in pH, SAR and PS than non‐eroded ones. The ESP (exchangeable sodium percentage) of the eroded slope has a higher value than the non‐eroded one. Crusts are less dispersive than eroded substrates, and non‐eroded substrates behave as crusts. This suggests that the portion of the slope most severely exposed to weathering tends to stabilize, due to strong decreases in SAR, PS and ESP. Several diagrams reported in the literature show similarly anomalous crust samples on eroded slopes, compared with other samples coming from greater depths on eroded slopes. In the present case study, the exchangeable form of Na characterizes crusts more than the soluble form.

This study describes the erosional mechanism, which involves morphological and geographic exposure and climatic elements, as well as grain size, mineralogy, chemistry and exchangeable processes of soils. Copyright © 2006 John Wiley & Sons, Ltd.
Composition and antimicrobial activity of the essential oil of Clinopodium ascendens (Jordan) Sampaio from Madeira
Authors: Castilho Paula , Liu Kai , Rodrigues Ana Isabel , Feio Sónia , Tomi Félix , Casanova Joseph
Published: December 2006

Clinopodium ascendens (Jordan) Sampaio [synonyms = Calamintha ascendens Jordan = C. officinalis Moench ssp. ascendens (Jord.) Mateo = C. sylvatica Bromf. ssp. ascendens (Jord.) P.W. Ball] is a small herbaceous plant with a very strong and distinctive mint aroma. The plant is known for its medical uses in folk medicine and as a spice in Italian kitchens. In Madeira Island, Clinopodium ascendens, known locally as ‘neveda’, grows wild along the shady paths of the Laurissilva forest. The local population uses the leaves of calamint as a mouth freshener and to alleviate headache and toothache. The essential oil obtained by hydrodistillation of the aerial parts of C. ascendens growing wild in Madeira was analysed by a combination of CC, GC, GC–MS, 1H‐ and 13C‐NMR. The oil was dominated by C3 oxygenated p‐menthane derivatives: cis‐isopulegone (75.2%), pulegone (6.9%), neoiso‐isopulegol (6.0%) and trans‐isopulegone (4.5%). The whole essential oil was tested against a variety of bacteria, both Gram‐positive and Gram‐negative, and two fungi; it exhibited remarkable activity against Escherichia coli and was active against Agrobacterium tumefasciens and Staphylococcus aureus and the phytopathogenic fungus Botrytis cinerea. It was ineffective against Streptococcus faecium, Streptococcus mutans and Candida albicans. Copyright © 2006 John Wiley & Sons, Ltd.
A probabilistic investigation of infiltration in the vadose zone: proposal for a new formula of infiltration rate
Authors: Carlier Erick
Published: December 2006

The infiltration rate in the unsaturated zone is analysed from a probabilistic point of view. It is shown that the empirical formulas of Horton and Kostiakov, without apparent physical basis, are explained in a probabilistic approach. Horton's formula reflects a Markovian process contrary to Kostiakov's formula. This approach made it possible to explain why Kostiakov's formula is more powerful than that of Horton. A new equation of infiltration is proposed. The three formulas were compared, for four types of soil, with the model of van Genuchten based on the Richards equation. Copyright © 2006 John Wiley & Sons, Ltd.
Transient and reversible nephrotoxicity of sarin in rats
Authors: Bloch‐Shilderman Eugenia , Levy Aharon
Published: December 2006

Organophosphate (OP) poisoning, which inhibits cholinesterase activity, leads to severe cholinergic symptoms. Effective and quick management of these symptoms is considered critical to the clinical outcome. Acute renal damage following exposure to OP insecticides has been reported. Similar complications might occur following exposure to OP nerve agents, however, this subject has been studied only sporadically. In the present study, the effect of the nerve agent sarin on renal function was examined in rats. A single dose of sarin (∼0.9 LD50) led to a significant reduction (of 45%) in renal function during the first 2 days post exposure, as exhibited by evaluation of the glomerular filtration rate, through measuring the clearance of 99mTc‐DTPA. The urine volume was reduced by 50%, the urine specific gravity increased to 104% of the control value and massive hematuria and glucosuria were recorded 24–48 h post exposure. In addition, around 60% decrease in urine electrolytes was monitored during the first 2 days following exposure, with a recovery after 8 days. Post mortem gross inspection of the bladder, 24 h post exposure, revealed severe edema and hemorrhage. Treatment with the muscarinic antagonist atropine and the oxime TMB‐4, at excessive doses administered 1 min post exposure, did not prevent most renal impairments. It has been concluded that sarin caused an acute renal dysfunction, possibly accompanied by bladder damage. These impairments were reversible, recovered spontaneously within 3–8 days, and were probably related to the state of shock and hypovolemia caused by the poisoning. However, if renal impairments are left unattended, they might contribute to the overall toxic manifestation and as a result aggravate the clinical state of intoxicated casualties. Copyright © 2006 John Wiley & Sons, Ltd.
Pelvic growth: Ontogeny of size and shape sexual dimorphism in rat pelves
Authors: Berdnikovs S. , Bernstein M. , Metzler A. , German R.Z.
Published: December 2006

The mammalian pelvis is sexually dimorphic with respect to both size and shape. Yet little is known about the differences in postnatal growth and bone remodeling that generate adult sexual dimorphism in pelvic bones. We used Sprague‐Dawley laboratory rats (Rattus norvegicus), a species that exhibits gross pelvic size and shape dimorphism, as a model to quantify pelvic morphology throughout ontogeny. We employed landmark‐based geometric morphometrics methodology on digitized landmarks from radiographs to test for sexual dimorphism in size and shape, and to examine differences in the rates, magnitudes, and directional patterns of shape change during growth. On the basis of statistical significance testing, the sexes became different with respect to pelvic shape by 36 days of age, earlier than the onset of size dimorphism (45 days), although visible shape differences were observed as early as at 22 days. Males achieved larger pelvic sizes by growing faster throughout ontogeny. However, the rates of shape change in the pelvis were greater in females for nearly all time intervals scrutinized. We found that trajectories of shape change were parallel in the two sexes until age of 45 days, suggesting that both sexes underwent similar bone remodeling until puberty. After 45 days, but before reproductive maturity, shape change trajectories diverged because of specific changes in the female pelvic shape, possibly due to the influence of estrogens. Pattern of male pelvic bone remodeling remained the same throughout ontogeny, suggesting that androgen effects on male pelvic morphology were constant and did not contribute to specific shape changes at puberty. These results could be used to direct additional research on the mechanisms that generate skeletal dimorphisms at different levels of biological organization. J. Morphol., 2006. © 2006 Wiley‐Liss, Inc.
Linking form and function of the fibrous joints in the skull: A new quantification scheme for cranial sutures using the extant fish Polypterus endlicherii
Authors: Markey Molly J. , Marshall Charles R.
Published: December 2006

The aim of this study is to connect specific sutural morphologies with the specific types of deformation they experience. To meet this goal, we quantified the morphologies of the interfrontal (IF), interparietal (IP), and frontoparietal (FP) sutures in the extant fish Polypterus endlicherii, and used our published measurements of in vivo deformation of these sutures during feeding to infer how suture morphology and function are connected. Specifically, we found that three relatively simple measures of cross‐sectional suture complexity (i.e., the ratio of total sutural length to its shortest end‐to‐end length; amount of sutural overlap; and size of the largest interdigitation) can be used to distinguish between the IF, FP, and IP sutures, which exhibit very different cross‐sectional shapes and responses to loading. Interestingly, these differences in cross‐sectional morphology are not reflected by the linear traces of these sutures on the surface of the skull, implying that cross‐sectional shape of a suture must be known to infer the loading conditions it experiences. Plotting the three cross‐sectional metrics against one another to yield a sutural morphospace shows that the IF, IP, and FP sutures define regions that are largely distinct from one another. Our previous measurements of strain across these sutures suggested that the FP region would lie between the IF and IP regions; instead, the FP region is largely set apart from the other two fields. Based on this discovery, and on the locations of cranial muscles, we propose a new model of deformation in the skull of P. endlicherii during feeding, in which rotation parallel to the skull roof is combined with bending, subjecting the FP suture to complex shearing. Finally, although the sutures of P. endlicherii appear to be significantly less complex than those of mammals, these fish sutures show a similar range of morphologies and perform similar functions as do mammalian sutures. J. Morphol., 2007. © 2006 Wiley‐Liss, Inc.
Ultrastructural examination of spermiogenesis within the testis of the ground skink, Scincella laterale (Squamata, Sauria, Scincidae)
Authors: Gribbins Kevin M. , Mills Erin M. , Sever David M.
Published: December 2006

Although the events of spermiogenesis are commonly studied in amniotes, the amount of research available for lizards (Sauria) is lacking. Many studies have described the morphological characteristics of mature spermatozoa in lizards, but few detail the ultrastructural changes that occur during spermiogenesis. The purpose of this study was to gain a better understanding of the subcellular events of spermiogenesis within the temperate ground skink (Scincella laterale). The morphological data presented here represent the first complete ultrastructural study of spermiogenesis within the Scincidae clade. Samples of testes from 20 specimens were prepared using standard techniques for transmission electron microscopy. Many of the ultrastructural changes occurring during spermiogenesis within the ground skink are similar to that of other saurians. However, there were a few unique characteristics that to date have not been described during spermiogenesis in other lizards. For example, during early round spermatid development within the ground skink testis, proacrosomal granules begin to form within the acrosomal vesicle before making contact with the apex of the nucleus. Also, a prominent microtubular manchette develops during spermiogenesis; however, the circular component of the manchete is absent in this species of skink. This developmental difference in manchette formation may lead to the more robust and straight mature spermatozoa that are common within the Scincidae family. These anatomical character differences may be valuable nontraditional sources that along with more traditional sources (i.e., mitochondrial DNA) may help elucidate phylogenetic relationships, which are historically considered controversial at best, among species within Scincidae and Sauria. J. Morphol., 2007. © 2006 Wiley‐Liss, Inc.
Do collisions inside the collision cell play a relevant role in CID‐LIFT experiments?
Authors: Moneti Gloriano , Francese Simona , Mastrobuoni Guido , Pieraccini Giuseppe , Seraglia Roberta , Valitutti Giovanni , Traldi Pietro
Published: December 2006

Collision experiments are a valid approach to characterize the ionic species generated by matrix assisted laser desorption ionization (MALDI). When a time‐of‐flight analyzer is employed, three different approaches are available for these experiments: the postsource decay (PSD), the LIFT and the MALDI‐TOF/TOF. The last two are of particular interest because of the overcoming of the PSD problems related to mass calibration of the product ion spectra.

Experiments performed by LIFT on linear or cyclic peptides, in presence or in absence of collision gas in the collision cell, gave evidence of an unexpected behavior: the two spectra were practically superimposable, and in the former case only a few new fragmentation channels were activated with low yield. These results mean that the selected ion exhibits a large amount of internal energy, capable of promoting fragmentation processes in the time window corresponding to the flight time between ion source and the acceleration electrode placed after the collision cell.

Experiments performed by varying the plume density show that this internal energy uptake occurs in the expanding plume, through multiple collisions. The LIFT data have been compared with those achieved by collisions of ESI‐generated [MH]+ ions of angotensin II performed under ‘in‐source’ conditions and by triple‐quadrupole experiments. The obtained results show a strong similarity among the spectra, indicating that the internal energy uptake in a MALDI source is comparable with that of 40‐eV ions colliding with Ar in a triple‐quadrupole instrument. Copyright © 2006 John Wiley & Sons, Ltd.