bluuebunny/crossref_metadata_2025 huggingface dataset:
Kainate Seizures Cause Acute Dendritic Injury and Actin DepolymerizationIn Vivo
Authors: Zeng Ling-Hui , Xu Lin , Rensing Nicholas R. , Sinatra Philip M. , Rothman Steven M. , Wong Michael
Published: October 2007

Seizures may cause brain injury via a variety of mechanisms, potentially contributing to cognitive deficits in epilepsy patients. Although seizures induce neuronal death in some situations, they may also have “nonlethal” pathophysiological effects on neuronal structure and function, such as modifying dendritic morphology. Previous studies involving conventional fixed tissue analysis have demonstrated a chronic loss of dendritic spines after seizures in animal models and human tissue. More recently,in vivotime-lapse imaging methods have been used to monitor acute changes in spines directly during seizures, but documented spine loss only under severe conditions. Here, we examined effects of secondary generalized seizures induced by kainate, on dendritic structure of neocortical neurons using multiphoton imaging in live micein vivoand investigated molecular mechanisms mediating these structural changes. Higher-stage kainate-induced seizures caused dramatic dendritic beading and loss of spines within minutes, in the absence of neuronal death or changes in systemic oxygenation. Although the dendritic beading improved rapidly after the seizures, the spine loss recovered only partially over a 24 h period. Kainate seizures also resulted in activation of the actin-depolymerizing factor, cofilin, and a corresponding decrease in filamentous actin, indicating that depolymerization of actin may mediate the morphological dendritic changes. Finally, an inhibitor of the calcium-dependent phosphatase, calcineurin, antagonized the effects of seizures on cofilin activation and spine morphology. These dramaticin vivofindings demonstrate that seizures produce acute dendritic injury in neocortical neurons via calcineurin-dependent regulation of the actin cytoskeleton, suggesting novel therapeutic targets for preventing seizure-induced brain injury.
LKB1 Regulates Neuronal Migration and Neuronal Differentiation in the Developing Neocortex through Centrosomal Positioning
Authors: Asada Naoyuki , Sanada Kamon , Fukada Yoshitaka
Published: October 2007

The cerebral cortex is formed through the coordination of highly organized cellular processes such as neuronal migration and neuronal maturation. Polarity establishment of neurons and polarized regulation of the neuronal cytoskeleton are essential for these events. Here we find that LKB1, the closest homolog of theCaenorhabditis eleganspolarity protein Par4, is expressed in the developing neocortex. Knock-down of LKB1 in migrating immature neurons impairs neuronal migration, with alteration of the centrosomal positioning and with uncoupling between the centrosome and nucleus. Furthermore, impairment of LKB1 in differentiating neurons within the cortical plate induces malpositioning of the centrosome at the basal side of the nucleus, instead of the normal apical positioning. This is accompanied with the disruption of axonal and dendritic polarity, resulting in reversed orientation of differentiating neurons. Moreover, LKB1 specifies axon and dendrites identityin vitro. Together, these observations indicate that LKB1 plays a critical role in neuronal migration and neuronal differentiation. Furthermore, we propose that proper neuronal migration and differentiation are intimately coupled to the precise control of the centrosomal positioning/movement directed by LKB1.
A Role of the Transient Receptor Potential Domain of Vanilloid Receptor I in Channel Gating
Authors: García-Sanz Nuria , Valente Pierluigi , Gomis Ana , Fernández-Carvajal Asia , Fernández-Ballester Gregorio , Viana Felix , Belmonte Carlos , Ferrer-Montiel Antonio
Published: October 2007

Transient receptor potential vanilloid receptor subtype 1 (TRPV1) is an ionotropic receptor activated by temperature and chemical stimuli. The C-terminal region that is adjacent to the channel gate, recognized as the TRP domain, is a molecular determinant of receptor assembly. However, the role of this intracellular domain in channel function remains elusive. Here, we show that replacement of the TRP domain of TRPV1 with the cognate region of TRPV channels (TRPV2–TRPV6) did not affect receptor assembly and trafficking to the cell surface, although those receptors containing the TRP domain of the distantly related TRPV5 and TRPV6 did not display ion channel activity. Notably, functional chimeras exhibited an impaired sensitivity to the activating stimuli, consistent with a significant contribution of this protein domain to channel function. At variance with TRPV1, voltage-dependent gating of chimeric channels could not be detected in the absence of capsaicin and/or heat. Biophysical analysis of functional chimeras revealed that the TRP domain appears to act as a molecular determinant of the activation energy of channel gating. Together, these findings uncover a role of the TRP domain in intersubunit interactions near the channel gate that contribute to the coupling of stimulus sensing to channel opening.
Expression Profiling of Huntington's Disease Models Suggests That Brain-Derived Neurotrophic Factor Depletion Plays a Major Role in Striatal Degeneration
Authors: Strand Andrew D. , Baquet Zachary C. , Aragaki Aaron K. , Holmans Peter , Yang Lichuan , Cleren Carine , Beal M. Flint , Jones Lesley , Kooperberg Charles , Olson James M. , Jones Kevin R.
Published: October 2007

Many pathways have been proposed as contributing to Huntington's disease (HD) pathogenesis, but generally thein vivoeffects of their perturbation have not been compared with reference data from human patients. Here we examine how accurately mechanistically motivated and genetic HD models recapitulate the striatal gene expression phenotype of human HD. The representative genetic model was the R6/2 transgenic mouse, which expresses a fragment of the huntingtin protein containing a long CAG repeat. Pathogenic mechanisms examined include mitochondrial dysfunction; profiled in 3-nitropropionic acid-treated rats, 1-methyl-4-phenyl-1,2,3,6-tetrahydropyridine-treated mice, andPGC-1α knock-out mice; and depletion of brain-derived neurotrophic factor (BDNF) using heterozygous and forebrain-specific BDNF-knock-out mice (BDNFHET,Emx-BDNFKO). Based on striatal gene expression, we find the BDNF models, both heterozygous and homozygous knock-outs, to be more like human HD than the other HD models. This implicates reduced trophic support as a major pathway contributing to striatal degeneration in HD. Because the majority of striatal BDNF is synthesized by cortical neurons, the data also imply that cortical dysfunction contributes to HD's hallmark effects on the basal ganglia. Finally, the results suggest that striatal lesions caused by mitochondrial toxins may arise via pathways different from those that drive neurodegeneration in HD. Based on these findings, we present a testable model of HD pathogenesis that, unlike most models, begins to account for regional specificity in human HD and the absence of such specificity in genetic mouse models of HD.
Patterning the Dorsal Telencephalon: A Role for Sonic Hedgehog?
Authors: Rash Brian G. , Grove Elizabeth A.
Published: October 2007

Division of the telencephalic vesicle into hemispheres and specification of the cerebral cortex are key stages in forebrain development. We investigate the interplay in these processes of Sonic hedgehog (Shh), fibroblast growth factors (Fgfs), and the transcription factor Gli3, which in its repressor form (Gli3R) antagonizes Shh signaling and downregulates expression of severalFgfgenes.

Contrary to previous reports, Shh is not required for dorsal hemisphere separation. Mice lacking Shh develop a dorsal telencephalic midline, a cortical hem, and two cortical hemispheres. The hemispheres do not divide rostrally, probably because of reduced localFgfgene expression, resulting from the loss of Shh inhibition of Gli3R. Removing one functional copy ofGli3substantially rescuesFgfexpression and rostral telencephalic morphology.

In mice lacking Gli3 function, cortical development is arrested, and ventral gene expression invades the dorsal telencephalon. These defects are potentially explained by disinhibition of Shh activity. However, when both copies ofShhare removed from Gli3-null mice, dorsal telencephalic defects persist. One such defect is a large dorsal expansion of the expression ofFgfgenes.Fgf15expression, for example, expands from a discrete ventral domain throughout the dorsal telencephalon. We propose that Fgf signaling, known to ventralize the telencephalon in a Shh-independent manner, suppresses cortical fate in the absence of Gli3. Our findings point away from Shh involvement in dorsal telencephalic patterning and encourage additional exploration of Fgf signaling and Gli3 repression in corticogenesis.
The Role of the PDZ Protein GIPC in Regulating NMDA Receptor Trafficking
Authors: Yi Zhaohong , Petralia Ronald S. , Fu Zhanyan , Swanwick Catherine Croft , Wang Ya-Xian , Prybylowski Kate , Sans Nathalie , Vicini Stefano , Wenthold Robert J.
Published: October 2007

The NMDA receptor is an important component of excitatory synapses in the CNS. In addition to its synaptic localization, the NMDA receptor is also present at extrasynaptic sites where it may have functions distinct from those at the synapse. Little is known about how the number, composition, and localization of extrasynaptic receptors are regulated. We identified a novel NMDA receptor-interacting protein, GIPC (GAIP-interacting protein, C terminus), that associates with surface as well as internalized NMDA receptors when expressed in heterologous cells. In neurons, GIPC colocalizes with a population of NMDA receptors on the cell surface, and changes in GIPC expression alter the number of surface receptors. GIPC is mainly excluded from the synapse, and changes in GIPC expression do not change the total number of synaptic receptors. Our results suggest that GIPC may be preferentially associated with extrasynaptic NMDA receptors and may play a role in the organization and trafficking of this population of receptors.
Defects in Embryonic Neurogenesis and Initial Synapse Formation in the Forebrain of the Ts65Dn Mouse Model of Down Syndrome
Authors: Chakrabarti Lina , Galdzicki Zygmunt , Haydar Tarik F.
Published: October 2007

Trisomy 21, one of the most prevalent congenital birth defects, results in a constellation of phenotypes collectively termed Down syndrome (DS). Mental retardation and motor and sensory deficits are among the many debilitating symptoms of DS. Alterations in brain growth and synaptic development are thought to underlie the cognitive impairments in DS, but the role of early brain development has not been studied because of the lack of embryonic human tissue and because of breeding difficulties in mouse models of DS. We generated a breeding colony of the Ts65Dn mouse model of DS to test the hypothesis that early defects in embryonic brain development are a component of brain dysfunction in DS. We found substantial delays in prenatal growth of the Ts65Dn cerebral cortex and hippocampus because of longer cell cycle duration and reduced neurogenesis from the ventricular zone neural precursor population. In addition, the Ts65Dn neocortex remains hypocellular after birth and there is a lasting decrease in synaptic development beginning in the first postnatal week. These results demonstrate that specific abnormalities in embryonic forebrain precursor cells precede early deficits in synaptogenesis and may underlie the postnatal disabilities in Ts65Dn and DS. The early prenatal period is therefore an important new window for possible therapeutic amelioration of the cognitive symptoms in DS.
Stress-Induced p38 Mitogen-Activated Protein Kinase Activation Mediates κ-Opioid-Dependent Dysphoria
Authors: Bruchas Michael R. , Land Benjamin B. , Aita Megumi , Xu Mei , Barot Sabiha K. , Li Shuang , Chavkin Charles
Published: October 2007

The molecular mechanisms mediating stress-induced dysphoria in humans and conditioned place aversion in rodents are unknown. Here, we show that repeated swim stress caused activation of both κ-opioid receptor (KOR) and p38 mitogen-activated protein kinase (MAPK) coexpressed in GABAergic neurons in the nucleus accumbens, cortex, and hippocampus. Sites of activation were visualized using phosphoselective antibodies against activated κ receptors (KOR-P) and against phospho-p38 MAPK. Surprisingly, the increase in P-p38-IR caused by swim-stress exposure was completely KOR dependent; P-p38-IR did not increase in KOR(−/−) knock-out mice subjected to the same swim-paradigm or in wild-type mice pretreated with the KOR antagonist norbinaltorphimine. To understand the relationship between p38 activation and the behavioral effects after KOR activation, we administered the p38 inhibitor SB203580 [4-(4-fluorophenyl)-2-(4-methylsulfonylphenyl)-5-(4-pyridyl)-1H-imidazole (i.c.v.)] and found that it selectively blocked the conditioned place aversion caused by the κ agonist trans-3,4-dichloro-N-methyl-N-[2-(1-pyrrolidinyl)cyclohexyl]-benzeneacetamide (U50488) and the KOR-dependent swim stress-induced immobility while not affecting κ-opioid analgesia or nonselectively affecting associative learning. We found that the mechanism linking KOR and p38 activationin vivowas consistent with our previousin vitrodata suggesting that β-arrestin recruitment is required; mice lacking G-protein-coupled receptor kinase 3 also failed to increase p-p38-IR after KOR activationin vivo, failed to show swim stress-induced immobility, or develop conditioned place aversion to U50488. Our results indicate that activation of p38 MAPK signaling by the endogenous dynorphin-κ-opioid system likely constitutes a key component of the molecular mechanisms mediating the aversive properties of stress.
Regulation of NaV1.2 Channels by Brain-Derived Neurotrophic Factor, TrkB, and Associated Fyn Kinase
Authors: Ahn Misol , Beacham Daniel , Westenbroek Ruth E. , Scheuer Todd , Catterall William A.
Published: October 2007

Voltage-gated sodium channels are responsible for action potential initiation and propagation in neurons, and modulation of their function has an important impact on neuronal excitability. Sodium channels are regulated by a Src-family tyrosine kinase pathway, and this modulation can be reversed by specifically bound receptor phosphoprotein tyrosine phosphatase-β. However, the specific tyrosine kinase and signaling pathway are unknown. We found that the sodium channels in rat brain interact with Fyn, one of four Src-family tyrosine kinases expressed in the brain. NaV1.2 channels and Fyn are localized together in the axons of cultured hippocampal neurons, the mossy fibers of the hippocampus, and cell bodies, dendrites, and axons of neurons in many other brain areas, and they coimmunoprecipitate with Fyn from cotransfected tsA-201 cells. Coexpression of Fyn with NaV1.2 channels decreases sodium currents by increasing the rate of inactivation and causing a negative shift in the voltage dependence of inactivation. Reconstitution of a signaling pathway from brain-derived neurotrophic factor (BDNF) to sodium channels via the tyrosine receptor kinase B (TrkB)/p75 neurotrophin receptor and Fyn kinase in transfected cells resulted in an increased rate of inactivation of sodium channels and a negative shift in the voltage dependence of inactivation after treatment with BDNF. These results indicate that Fyn kinase is associated with sodium channels in brain neurons and can modulate NaV1.2 channels by tyrosine phosphorylation after activation of TrkB/p75 signaling by BDNF.
Misexpression of Pou3f1 Results in Peripheral Nerve Hypomyelination and Axonal Loss
Authors: Ryu Elizabeth J. , Wang James Y. T. , Le Nam , Baloh Robert H. , Gustin Jason A. , Schmidt Robert E. , Milbrandt Jeffrey
Published: October 2007

Pou3f1/SCIP/Oct-6 is a POU-domain transcription factor that is an important regulator of peripheral nerve myelination by Schwann cells. Pou3f1-deficient mice experience a developmental delay in myelination indicating that transient induction of Pou3f1 is required for normal development of peripheral myelin. The mechanism by which Pou3f1 regulates myelination is unclear, because it can both increase expression of Egr2, a transcription factor that promotes the myelination program, and also repress the promoters of specific myelin genes such as myelin protein zero (MPZ) and myelin basic protein (MBP). Therefore, to investigate the effects of persistent Pou3f1 expression on peripheral nerve myelination, we created a conditional transgenic mouse [condPou3f1:MPZ(Cre)] that constitutively expresses Pou3f1 specifically in peripheral glia. Examination of sciatic nerves from condPou3f1:MPZ(Cre) mice revealed persistent hypomyelination and eventual axonal loss but no evidence of demyelination/remyelination processes or impaired Schwann cell proliferation. Nerves from these mice had normal levels of Egr2 mRNA but decreased levels of MPZ, MBP, and Pmp22 mRNA. Thus, unlike the Pou3f1 null mice, the condPou3f1:MPZ(Cre) mice exhibit persistent hypomyelination, indicating that strict control of Pou3f1 expression is critical to proper myelination. Our findings establish the importance of identifying factor(s) responsible for Pou3f1 downregulation during myelination, because they may play important roles in the development of peripheral neuropathies.
Law and Society in Seattle: Law‐Related Education as Culturally Responsive Teaching
Authors: VanderStaay Steven L.
Published: October 2007

In this article, I provide a portrait (Sara Lawrence‐Lightfoot and Jessica Hoffman Davis 1997) of a renowned law‐related education (LRE) program, its teacher, and four of its student‐participants. Following the portrait, I discuss theoretical explanations for the success of ethnic‐minority students in this and other LRE programs. These explanations include the nature of law as a difficult subject, the many convergences between culturally responsive teaching and LRE, and the relation of the content and methods of LRE to the cultural capital, interests, backgrounds, and ethnic identities of the students. I conclude with a discussion of the reciprocal nature of these processes, research on white teachers who are successful in multicultural contexts, the importance of challenging, accelerated classes, and an argument for expanding research on culturally responsive teaching and the achievement of students of color to include attention to the methods and materials of LRE.
The Difference that Diaspora Makes: Thinking through the Anthropology of Immigrant Education in the United States
Authors: Lukose Ritty A.
Published: October 2007

In this article, I examine the possibility of a productive dialogue between diaspora studies and the anthropology of immigrant education in the United States. Arguing that their respective views on the nation‐state is a key source for their different orientations toward migrant social and cultural worlds, I nevertheless argue that an engagement between these two fields of study will yield more critical understandings of nationalism, the category of the “immigrant,” and multiculturalism within both these areas of scholarship.
Whither the Asian American Coalition?
Authors: Spickard Paul
Published: October 2007

This article offers a brief history of the Asian American coalition and suggests how possible new directions for the coalition in the future may affect the scope and preoccupations of Asian American history as it will be written. “Asian American” was an idea invented in the 1960s to bring together Chinese, Japanese, and Filipino Americans for strategic purposes. Soon other Asian-origin groups, such as Korean, Vietnamese, and South Asian Americans, were added. The article considers four groups who some people have suggested have strategic links with the Asian American coalition—Pacific Islander Americans, multiracial people of part-Asian descent, international adoptees from Asian countries, and Arab and other Middle Eastern Americans. It examines whether and how each group might be considered part of the Asian American coalition, and what impact their inclusion might have on the writing of Asian American history.
Engagement with Mathematics Courseware in Traditional and Online Remedial Learning Environments: Relationship to Self-Efficacy and Achievement
Authors: Spence Dianna J. , Usher Ellen L.
Published: October 2007

This research applied Bandura's (1986) social cognitive theory to examine engagement with courseware in traditional and online remedial mathematics learning environments. The study investigated the relationship of courseware engagement to age, computer self-efficacy, computer playfulness, and self-efficacy for self-regulated mathematics learning. The study also analyzed mathematics achievement in terms of engagement, age, gender, mathematics grade self-efficacy, and self-efficacy for self regulated mathematics learning. Participants were 88 students in a traditional environment and 76 students in an online environment. The two groups differed significantly in age, mathematics grade self-efficacy, computer self-efficacy, computer playfulness, courseware engagement, and mathematics achievement. When controlled for age, all significant differences found between the two groups persisted. When controlled for mathematics self-efficacy, the groups no longer differed significantly in mathematics achievement, but all other significant differences remained. Computer self-efficacy and computer playfulness each had a significant association with courseware engagement in the online environment, but not in the traditional environment. Regression models revealed that course setting, age, and self-efficacy for self-regulation jointly predicted engagement with courseware. Both mathematics grade self-efficacy and age jointly predicted achievement. These findings support the views that mathematics self-efficacy is among the most significant predictors of mathematics achievement; computer self-efficacy and computer playfulness are associated with courseware engagement; and self-regulation is an important component of e-learning. Implications for researchers and educators are discussed.
Three Explanations of Marital Status Differences in Suicide Rates: Social Integration, Marital Status Integration, and the Culture of Suicide
Authors: Cutright Phillips , Fernquist Robert M.
Published: October 2007

Our first goal is to link empirical measures of three theoretical explanations of marital status differences to the variation in male and female standardized suicide difference coefficients SSDCs in 12 developed countries, circa 1960. We include predictors of Durkheim's social integration hypothesis, Gibbs and Martin's concept of marital status integration, and norms on suicide acceptability. All three are significantly related to variation in male and female SSDCs. The second goal is to examine how our empirical indicators impact age-specific differences in the male minus female SSDC—differences that vary by age in all 12 of our study populations. The strongest predictor of these differences is the male minus female difference in the percent married.
Unaltered Diabetes Presentation in NOD Mice Lacking the Vitamin D Receptor
Authors: Gysemans Conny , van Etten Evelyne , Overbergh Lutgart , Giulietti Annapaula , Eelen Guy , Waer Mark , Verstuyf Annemieke , Bouillon Roger , Mathieu Chantal
Published: October 2007

OBJECTIVE— Vitamin D deficiency increases risk for type 1 diabetes in genetically predisposed individuals, while high doses of 1,25-dihydroxyvitamin D3 [1,25(OH)2D3] prevent insulitis and diabetes in NOD mice.

RESEARCH DESIGN AND METHODS— Since 1,25(OH)2D3 regulates gene transcription through the vitamin D receptor (VDR), we investigated the role of VDR in diabetes development by creating NOD mice without functional VDR.

RESULTS— VDR−/− NOD mice are rachitic and have lower numbers of putative regulator cells [TCR-α/β+CD4−CD8− (natural killer T-cells) and CD4+CD25+ T-cells [in central and peripheral immune organs compared with VDR+/+ NOD littermates. Lipopolysaccharide-stimulated VDR−/− NOD macrophages expressed lower interleukin (IL)-1, IL-6, and CC chemokine ligand 2 mRNA, correlating with less nuclear translocation of p65 nuclear factor-κB compared with VDR+/+ NOD macrophages. Thymic and lymph node dendritic cells from VDR−/− NOD mice displayed an even less mature CD11c+CD86+ phenotype than VDR+/+ NOD mice. Despite this immune phenotype linked to diabetes in NOD mice, VDR−/− NOD mice developed insulitis and diabetes at the same rate and incidence as VDR+/+ NOD littermates.

CONCLUSIONS— Despite aggravating known immune abnormalities in NOD mice, disruption of VDR does not alter disease presentation in NOD mice in contrast to the more aggressive diabetes presentation in vitamin D–deficient NOD mice.
Recent Chinese Buyout Activity and the Implications for Wider Global Investment Rules
Authors: Antkiewicz Agata , Whalley John
Published: October 2007

We discuss recent cases of Chinese buyout activity in the Organisation for Economic Co-operation and Development (OECD; especially in the United States and European Union) in resource and manufacturing sectors. While most of the buyout attempts have been unsuccessful, they serve as a catalyst for a wider discussion on the implications for global arrangements for cross-border acquisitions. Three specific issues are raised. The first is subsidization through low- or no-interest loans by the Chinese Central Bank to companies investing abroad. The second is the transparency of entities involved in buyout attempts. Most Chinese companies have close ties to multiple levels of government and are not subject to the standard reporting required of OECD companies. The third involves national security concerns in OECD countries and the possibility of China acquiring sensitive technology when Chinese companies purchase companies abroad. These issues have not been addressed in existing OECD and World Trade Organization investment policy initiatives, and have yet to be discussed in the global forum.
Parental Work Arrangements and Child Development
Authors: Waldfogel Jane
Published: October 2007

This article synthesizes what we know and do not know about the links between family work arrangements and child development, drawing on research from Canada, the United States, and the United Kingdom. The paper reviews the evidence about how parental employment affects children's cognitive development, social and emotional development, and health; summarizes knowledge gaps; and makes recommendations for future Canadian policy-oriented research.
Sinonasal adenoid cystic carcinoma
Authors: Lupinetti Allison D. , Roberts Dianna B. , Williams Michelle D. , Kupferman Michael E. , Rosenthal David I. , Demonte Franco , El‐Naggar Adel , Weber Randal S. , Hanna Ehab Y.
Published: October 2007

BACKGROUND.

Adenoid cystic carcinoma of the sinonasal tract is a rare cancer that accounts for 10% of all malignancies at this site. The objective of the current study was to evaluate prognostic factors, treatment outcomes, recurrence patterns, and survival rates for sinonasal adenoid cystic carcinoma.

METHODS.

A retrospective chart review was performed at an academic tertiary referral center. Between 1990 and 2004, 105 patients were evaluated for adenoid cystic carcinoma of the sinonasal tract at a single institution. Demographics, presentation, anatomic site, Tumor, Lymph Node, Metastasis (TNM) classification, pathology, treatment, recurrences, and survival were evaluated.

RESULTS.

One hundred five patients with adenoid cystic carcinoma were evaluated, including 58 women and 47 men. Their median age was 50 years, and the mean follow‐up was 47 months. The maxillary sinus (47%) and the nasal cavity (30%) were the most common primary tumor sites. The majority of patients presented with T3/T4 (76.7%), N0 (98%), M0 (97%) disease. Eighty‐four percent of patients underwent surgery and received postoperative radiation as treatment for their primary disease. The local recurrence rate was 30%, and the distant metastases rate was 38%. The 5‐year overall survival and disease specific survival rates were 62.9% and 70.9%, respectively.

CONCLUSIONS.

Adenoid cystic carcinoma of the paranasal sinuses is a rare disease, and the ideal treatment paradigm has yet to be defined. The current data suggested that surgical resection with postoperative radiation therapy offers durable local control and compares favorably with historic data. Although local recurrences develop in a significant percentage of patients, survival from this disease exceeds that of other sinonasal malignancies. Cancer 2007. © 2007 American Cancer Society.
Reactions of Sulphate Radicals with Substituted Pyridines: A Structure–Reactivity Correlation Analysis
Authors: Dell'Arciprete María L. , Cobos Carlos J. , Furlong Jorge P. , Mártire Daniel O. , Gonzalez Mónica C.
Published: October 2007

The kinetics of the oxidation of pyridine, 3‐chloropyridine, 3‐cyanopyridine, 3‐methoxypyridine and 3‐methylpyridine mediated by SO4 radicals are studied by flash photolysis of peroxodisulphate, S2O82−, at pH 2.5 and 9. The absolute rate constants for the reactions of both, the basic and acid forms of the pyridines, are determined and discussed in terms of the Hammett correlation. The monosubstituted pyridines react about 10 times faster with sulphate radicals than their protonated forms, the pyridine ions. The organic intermediates are identified as the corresponding hydroxypyridine radical adducts and their absorption spectra compared with those estimated employing the time‐dependent density functional theory with explicit account for bulk solvent effects. A reaction mechanism which accounts for the observed intermediates and the pyridinols formed as products is proposed.
A simple method to approximate the probability of error for equal gain combiner over independent fading channels
Authors: Samimi Hossein , Azmi Paeiz
Published: October 2007

Using the Beaulieu series, the probability of error for equal gain combiner over independent fading channels can be formulated in the form of an infinite series. The computation of the coefficients of this series needs complicated integrations over fading envelope distribution. In this paper, a new approximation method is developed for the computation of the required coefficients of the error probability series, which needs only mean and variance of the fading envelope. Hence, the purposed method eliminates the need for complicated integrations while computing the required coefficients. This feature provides an interesting flexibility for our developed method, so that it can be used as a unified method for performance analysis of equal gain combiner over various independent fading channels, especially where the required integrations have no closed‐form solutions. To present an application for the proposed approximation method, the fading channel is modeled by three‐parameter generalized Gamma distribution (GG3), which is a generic model that covers many well‐known channel models for both multipath and shadow fading. The presented numerical results show good accuracy as well as low computational complexity of the presented method. Copyright © 2007 John Wiley & Sons, Ltd.
Fatty acid and conjugated linoleic acid isomer profiles in human milk fat
Authors: Luna Pilar , Juárez Manuela , de la Fuente Miguel Angel
Published: October 2007

The fatty acid composition of 39 mature human milk samples from four Spanish women collected between 2 and 18 weeks during lactation was studied by gas chromatography. The conjugated linoleic acid (CLA) isomer profile was also determined by silver‐ion HPLC (Ag+‐HPLC) with three columns in series. The major fatty acid fraction in milk lipids throughout lactation was represented by the monounsaturated fatty acids, with oleic acid being the predominant compound (36–49% of total fatty acids). The saturated fatty acid fraction represented more than 35% of the total fatty acids, and polyunsaturated fatty acids ranged on average between 10 and 13%. Mean values of total CLA varied from 0.12 to 0.15% of total fatty acids. The complex mixture of CLA isomers was separated by Ag+‐HPLC. Rumenic acid (RA, cis‐9 trans‐11 C18:2) was the major isomer, representing more than 60% of total CLA. Trans‐9 trans‐11 and 7‐9 (cis‐trans + trans‐cis) C18:2 were the main CLA isomers after RA. Very small amounts of 8‐10 and 10‐12 C18:2 (cis‐trans + trans‐cis) isomers were detected, as were different proportions of cis‐11 trans‐13 and trans‐11 cis‐13 C18:2. Although most of the isomers were present in all samples, their concentrations varied considerably.
Fast determination of prominent carotenoids in tomato fruits by CEC using methacrylate ester‐based monolithic columns
Authors: Adalid Ana Maria , Herrero‐Martínez José Manuel , Roselló Salvador , Maquieira Angel , Nuez Fernando
Published: October 2007

In this study, the major carotenoids (β‐carotene and lycopene) present in tomato fruits were analyzed by CEC with a methacrylate ester‐based monolithic column. The effects of the porogenic solvent ratio, and the hydrophobicity of bulk monomer employed were examined on carotenoids separations. A fast separation of these analytes was achieved in less than 5.0 min in a mobile phase containing 35% THF, 30% ACN, 30% methanol, and 5% of a 5 mM Tris aqueous buffer, pH 8, with lauryl methacrylate‐based monoliths. The CEC method was evaluated in terms of detection limit and reproducibility (retention time, area, and column preparation) with values below 1.6 μg/mL and 7.2%, respectively. The proposed procedure was successfully applied to the determination of both carotenoids in fruits of several tomato‐related species and its usefulness to analyze large series of samples for nutritional quality screening trials in tomato breeding programs is demonstrated. To our knowledge, this is the first work that exploits the powerful and user‐friendly monolithic technology for quality breeding and germplasm evaluation program purposes.
CE: A useful analytical tool for the characterization of Maillard reaction products in foods
Authors: Vallejo‐Cordoba Belinda , González‐Córdova Aarón F.
Published: October 2007

The Maillard reaction (MR) is a complex series of nonenzymatic reactions between reducing compounds and amines, amino acids, peptides, or proteins that play an important role in the formation of flavors and colors in foods during processing and storage. Also, the antioxidant properties of some Maillard reaction products (MRP) was an additional benefit reported. On the other hand, these reactions decrease the nutritional quality of foods and may result in the formation of toxic MRP. Although, research to assess the risks and benefits associated with the consumption of MRP in the diet is still awaiting for new analytical methodologies to be developed. Structural characterization of MRP has been very challenging due to the chemical diversity of these compounds which present a wide range of polarities and molecular weights, making analyses difficult. CE is a technique that has gained popularity for the separation of complex mixtures that have otherwise proved difficult to analyze. Thus, the purpose of this overview is to give the reader an appreciation of some of the CE analytical developments on the analysis of MRP in model systems and foods, and to address the potential of CE on the characterization of this complex group of compounds.
The amygdala modulates neuronal activation in the hippocampus in response to spatial novelty
Authors: Sheth Archana , Berretta Sabina , Lange Nicholas , Eichenbaum Howard
Published: October 2007

Emerging evidence indicates that the amygdala and the hippocampus play an important role in the pathophysiology of major psychotic disorders. Consistent with this evidence, and with data indicating amygdala modulation of hippocampal activity, animal model investigations have shown that a disruption of amygdala activity induces neurochemical changes in the hippocampus that are similar to those detected in subjects with schizophrenia. With the present study, we used induction of the immediate early gene Fos, to test the hypothesis that the amygdala may affect neuronal activation of the hippocampus in response to different spatial environments (familiar, modified, and novel). Exploratory and anxiety related behaviors were also assessed. In vehicle‐treated rats, exposure to a modified version of the familiar environment was associated with an increase of numerical densities of Fos‐immunoreactive nuclei in sectors CA1 and CA2, while exposure to a completely novel environment was associated with an increase in sectors CA1, CA4, and DG, compared with the familiar environment. Pharmacological disruption of amygdala activity resulted in a failure to increase Fos induction in the hippocampus in response to these environments. Exploratory behavior in response to the different environments was not altered by manipulation of amygdala activity. These findings support the idea that the amygdala modulates spatial information processing in the hippocampus and may affect encoding of specific environmental features, while complex behavioral responses to environment may be the result of broader neural circuits. These findings also raise the possibility that amygdala abnormalities may contribute to impairments in cognitive information processing in subjects with major psychoses. © 2007 Wiley‐Liss, Inc.
Prognostic effect of estrogen receptor status across age in primary breast cancer
Authors: Bentzon Niels , Düring Maria , Rasmussen Birgitte Bruun , Mouridsen Henning , Kroman Niels
Published: October 2007

Estrogen receptor (ER) status is considered as an important prognostic factor as well as a predictive factor for endocrine responsiveness in breast cancer. We analyzed the distribution of ER status across age and estimated variations in the prognostic impact of ER status related to patients' age and time since diagnosis. Overall, 26,944 patients with primary breast cancer diagnosed from 1989 to 2004 were included. The proportion of ER positive tumors increased over age from 51 to 82%. In multivariate analysis of overall survival, ER positive status was found to be a significantly positive prognostic factor over all age groups. This effect was limited to the first 5 years after diagnosis, RR: 2.08 (95% CI: 1.95–2.22, p < 0.0001). Overall survival during the following 5 years was slightly superior for women with ER negative tumors, RR of death: 0.89 (95% CI: 0.79–1.00, p = 0.049). Results were unchanged in patients who did not receive adjuvant systemic therapy (n = 6,272). Thus, positive ER status does not confer a negative impact on survival in young women as has been previously reported. The inferior prognosis for ER negative patients during the first 5 years after diagnosis changes into a slightly superior residual prognosis compared to ER positive patients independent of use of adjuvant systemic therapy. This may have an impact on future designing of guidelines for adjuvant endocrine therapy beyond 5 years. © 2007 Wiley‐Liss, Inc.
Relevance of a new rat model of osteoblastic metastases from prostate carcinoma for preclinical studies using zoledronic acid
Authors: Lamoureux François , Ory Benjamin , Battaglia Séverine , Pilet Paul , Heymann Marie‐Françoise , Gouin François , Duteille Franck , Heymann Dominique , Redini Françoise
Published: October 2007

Animal models that mimic osteoblastic metastases associated with prostate carcinoma are required to improve the therapeutic options in humans. A new model was then developed and characterized in immunocompetent rats. The bisphosphonate zoledronic acid (ZOL) was tested to validate this model as a therapeutic application. Rat AT6‐1 prostate tumor cells were characterizedin vitroat the transcriptional (bone and epithelial markers) and functional (induction of mineralized nodules) levels. The bone lesions induced after their direct injection into the femur bone marrow were characterized by radiography, microscanner and histology analyses. ZOL effects were studiedin vivoon bone lesion development andin vitroon AT6‐1 cell proliferation, apoptosis and cell cycle analysis. Apart from epithelial markers, AT6‐1 cells express an osteoblast phenotype as they express osteoblastic markers and are able to induce mineralized nodule formation in vitro. A disorganization of the trabecular bone at the growth zone level was observedin vivoafter intraosseous AT6‐1 cell injection as well as cortical erosion. The tumor itself is associated with bone formation as revealed by SEM analysis and polarized light microscopy. ZOL prevents the development of such osteoblastic lesions, related to a direct inhibitory effect on tumor cell proliferation independent of caspase 3 activation, but associated with cell cycle arrest. A new rat model of osteoblastic bone metastases was validated in immunocompetent rats and used to show the relevance of using ZOL in such lesions, as this compound shows bifunctional effects on both bone remodelling and tumor cell proliferation. © 2007 Wiley‐Liss, Inc.
Characterization of the antibodies to p62 nucleoporin in primary biliary cirrhosis using human recombinant antigen
Authors: Węsierska‐Gądek Józefa , Klima Anna , Ranftler Carmen , Komina Oxana , Hanover John , Invernizzi Pietro , Penner Edward
Published: October 2007

Reactivity of sera from patients with primary biliary cirrhosis (PBC) with a 60 kDa component of nuclear pore complexes (NPCs), purified by affinity chromatography on wheat‐germ agglutinin (WGA)‐Sepharose, was previously detected. Recently, clinical significance of the anti‐NPC antibodies in PBC became evident. In the light of recent reports, indicating the correlation of the anti‐NPC antibodies with severity and progression of the disease, the characterization of the reactive antigens is becoming essential in the clinical management of patients with PBC. Since accurate autoantibody detection represents one of the fundamental requirements for a reliable testing, we have generated a human recombinant p62 protein and validated an immunoprecipitation assay for the detection of anti‐p62. We also demonstrated that the generated human recombinant p62 nucleoporin was modified by N‐acetylglucosamine residues. More than 50% of tested PBC sera precipitated 35S‐radioactively labeled p62 recombinant nucleoporin and 40% recognized this recombinant antigen by immunoblotting. We compared the reactivity of PBC sera with rat and human nucleoporin. The incidence of anti‐p62 nucleoporin positive PBC sera increased by 15% when human recombinant antigen was used. The titer of autoantibodies in p62‐positive PBC samples strongly varied. Preadsorption of the PBC sera with p62 recombinant protein completely abolished their reactivity with the antigen. In conclusion, this study unequivocally proves that autoantibodies reacting with the 60 kDa component of NPCs target p62 nucleoporin and, more importantly, provide a better antigen source for future evaluations of the clinical role of anti‐p62 in PBC. J. Cell. Biochem. 104: 27–37, 2008. © 2007 Wiley‐Liss, Inc.
Activation of AMP‐activated protein kinase, inhibition of pyruvate dehydrogenase activity, and redistribution of substrate partitioning mediate the acute insulin‐sensitizing effects of troglitazone in skeletal muscle cells
Authors: Fediuc S. , Pimenta A.S. , Gaidhu M.P. , Ceddia R.B.
Published: October 2007

The aim of this study was to investigate the acute effects of troglitazone on several pathways of glucose and fatty acid (FA) partitioning and the molecular mechanisms involved in these processes in skeletal muscle. Exposure of L6 myotubes to troglitazone for 1 h significantly increased phosphorylation of AMPK and ACC, which was followed by ∼30% and ∼60% increases in palmitate oxidation and carnitine palmitoyl transferase‐1 (CPT‐1) activity, respectively. Troglitazone inhibited basal (∼25%) and insulin‐stimulated (∼35%) palmitate uptake but significantly increased basal and insulin‐stimulated glucose uptake by ∼2.2‐ and 2.7‐fold, respectively. Pharmacological inhibition of AMPK completely prevented the effects of troglitazone on palmitate oxidation and glucose uptake. Interestingly, even though troglitazone exerted an insulin sensitizing effect, it reduced basal and insulin‐stimulated rates of glycogen synthesis, incorporation of glucose into lipids, and glucose oxidation to values corresponding to ∼30%, ∼60%, and 30% of the controls, respectively. These effects were accompanied by an increase in basal and insulin‐stimulated phosphorylation of AktThr308, AktSer473, and GSK3α/β. Troglitazone also powerfully suppressed pyruvate decarboxylation, which was followed by a significant increase in basal (∼3.5‐fold) and insulin‐stimulated (∼5.5‐fold) rates of lactate production by muscle cells. In summary, we provide novel evidence that troglitazone exerts acute insulin sensitizing effects by increasing FA oxidation, reducing FA uptake, suppressing pyruvate dehydrogenase activity, and shifting glucose metabolism toward lactate production in muscle cells. These effects seem to be at least partially dependent on AMPK activation and may account for potential acute PPAR‐γ‐independent anti‐diabetic effects of thiazolidinediones in skeletal muscle. J. Cell. Physiol. 215: 392–400, 2008. © 2007 Wiley‐Liss, Inc.
Polymeric integrated selective enrichment target (ISET) for solid‐phase‐based sample preparation in MALDI–TOF MS
Authors: Ekström Simon , Wallman Lars , Helldin Göran , Nilsson Johan , Marko‐Varga György , Laurell Thomas
Published: October 2007

A polymer microfabricated proteomic sample preparation and MALDI MS sample presentation device, the integrated selective enrichment target (ISET), comprising an array of perforated nanovials is reported. Each perforated nanovial can be filled with selective extraction media (microbeads) for purification and concentration of protein/peptides prior to matrix‐assisted laser desorption/ionization mass spectrometry (MALDI MS). The main areas covered are the influence of the molding‐process‐induced surface roughness and how to address the lack of inherent conductivity in the polyetheretherketone (PEEK) material for optimal MALDI MS readout. Application of the disposable polymeric ISET devices for solid‐phase extraction and phosphopeptide capture is also demonstrated. Copyright © 2007 John Wiley & Sons, Ltd.
Study of protein targets for covalent modification by the antitumoral and anti‐inflammatory prostaglandin PGA1: focus on vimentin
Authors: Gharbi Severine , Garzón Beatriz , Gayarre Javier , Timms John , Pérez‐Sala Dolores
Published: October 2007

Prostaglandins with cyclopentenone structure (cyPG) display potent antiproliferative actions that have elicited their study as potential anticancer agents. Several natural and synthetic analogs of the cyPG prostaglandin A1 (PGA1) have proven antitumoral efficacy in cancer cell lines and animal models. In addition, PGA1 has been used as an inhibitor of transcription factor NF‐κB‐mediated processes, including inflammatory gene expression and viral replication. An important determinant for these effects is the ability of cyPG to form Michael adducts with free thiol groups. The chemical nature of this interaction implies that PGA1 could covalently modify cysteine residues in a large number of cellular proteins potentially involved in its beneficial effects. However, only a few targets of PGA1 have been identified. In previous work, we have observed that a biotinylated analog of PGA1 that retains the cyclopentenone moiety (PGA1‐B) binds to multiple targets in fibroblasts. Here, we have addressed the identification of these targets through a proteomic approach. Cell fractionation followed by avidin affinity chromatography yielded a fraction enriched in proteins modified by PGA1‐B. Analysis of this fraction by SDS‐PAGE and LC‐MS/MS allowed the identification of the chaperone Hsp90, elongation and initiation factors for protein synthesis and cytoskeletal proteins including actin, tubulin and vimentin. Furthermore, we have characterized the modification of vimentin both in vitro and in intact cells. Our observations indicate that cysteine 328 is the main site for PGA1 addition. These results may contribute to a better understanding of the mechanism of action of PGA1 and the potential of cyPG‐based therapeutic strategies. Copyright © 2007 John Wiley & Sons, Ltd.