bluuebunny/crossref_metadata_2025 huggingface dataset:
Modulatory effects ofN-acetyl-l-cysteine on human eosinophil apoptosis
Authors: Martinez-Losa M. , Cortijo J. , Juan G. , Ramón M. , Sanz M. J. , Morcillo E. J.
Published: May 2007

Eosinophils are oxidant-sensitive cells considered relevant in allergic inflammation. The present study aimed to examine the effects of the antioxidantN-acetyl-l-cysteine (NAC) on constitutive and cytokine-delayed apoptosis in human isolated eosinophils.

Human eosinophils were purified from the blood of healthy donors by a magnetic separation system. Apoptosis and cellular glutathione were assessed by cytofluorometric analysis and nuclear factor (NF)-κB binding activity assessed by electrophoresis mobility shift assay.

The rate of spontaneous apoptosis of human eosinophils after 24 h culture, as assessed by annexin-V-positive staining, was mean±sem 48.2±1.4%, n = 5. Granulocyte-macrophage colony-stimulating factor (GM-CSF; 10 ng·mL−1) decreased apoptosis to 19.4±1.8%, n = 5. NAC (5 mM) inhibited spontaneous apoptosis (33.6±2.7%, n = 5) but augmented apoptosis in the presence of GM-CSF (30.9±1.5%, n = 5). NAC (5 mM) also increased the rate of apoptosis in the presence of tumour necrosis factor (TNF)-α (10 ng·mL−1) and interleukin-5 (5 ng·mL−1). NAC (5 mM) increased eosinophil glutathione content. The increase in eosinophil NF-κB binding activity induced by GM-CSF and TNF-α was suppressed by NAC.

In conclusion,N-acetylcysteine modulates eosinophil apoptosis by inhibiting constitutive apoptosis but reversing the survival effect produced by inflammatory cytokines in human eosinophils.
Regulatory conservation of protein coding and microRNA genes in vertebrates: lessons from the opossum genome
Authors: Mahony Shaun , Corcoran David L , Feingold Eleanor , Benos Panayiotis V
Published: May 2007

Background

Being the first noneutherian mammal sequenced, Monodelphis domestica (opossum) offers great potential for enhancing our understanding of the evolutionary processes that take place in mammals. This study focuses on the evolutionary relationships between conservation of noncoding sequences, cis-regulatory elements, and biologic functions of regulated genes in opossum and eight vertebrate species.

Results

Analysis of 145 intergenic microRNA and all protein coding genes revealed that the upstream sequences of the former are up to twice as conserved as the latter among mammals, except in the first 500 base pairs, where the conservation is similar. Comparison of promoter conservation in 513 protein coding genes and related transcription factor binding sites (TFBSs) showed that 41% of the known human TFBSs are located in the 6.7% of promoter regions that are conserved between human and opossum. Some core biologic processes exhibited significantly fewer conserved TFBSs in human-opossum comparisons, suggesting greater functional divergence. A new measure of efficiency in multigenome phylogenetic footprinting (base regulatory potential rate [BRPR]) shows that including human-opossum conservation increases specificity in finding human TFBSs.

Conclusion

Opossum facilitates better estimation of promoter conservation and TFBS turnover among mammals. The fact that substantial TFBS numbers are located in a small proportion of the human-opossum conserved sequences emphasizes the importance of marsupial genomes for phylogenetic footprinting-based motif discovery strategies. The BRPR measure is expected to help select genome combinations for optimal performance of these algorithms. Finally, although the etiology of the microRNA upstream increased conservation remains unknown, it is expected to have strong implications for our understanding of regulation of their expression.
A global view of gene expression in lithium and zinc treated sea urchin embryos: new components of gene regulatory networks
Authors: Poustka Albert J , Kühn Alexander , Groth Detlef , Weise Vesna , Yaguchi Shunsuke , Burke Robert D , Herwig Ralf , Lehrach Hans , Panopoulou Georgia
Published: May 2007

Background

The genome of the sea urchin Strongylocentrotus purpuratus has recently been sequenced because it is a major model system for the study of gene regulatory networks. Embryonic expression patterns for most genes are unknown, however.

Results

Using large-scale screens on arrays carrying 50% to 70% of all genes, we identified novel territory-specific markers. Our strategy was based on computational selection of genes that are differentially expressed in lithium-treated embryos, which form excess endomesoderm, and in zinc-treated embryos, in which endomesoderm specification is blocked. Whole-mount in situ hybridization (WISH) analysis of 700 genes indicates that the apical organ region is eliminated in lithium-treated embryos. Conversely, apical and specifically neural markers are expressed more broadly in zinc-treated embryos, whereas endomesoderm signaling is severely reduced. Strikingly, the number of serotonergic neurons is amplified by at least tenfold in zinc-treated embryos. WISH analysis further indicates that there is crosstalk between the Wnt (wingless int), Notch, and fibroblast growth factor signaling pathways in secondary mesoderm cell specification and differentiation, similar to signaling cascades that function during development of presomitic mesoderm in mouse embryogenesis. We provide differential expression data for more than 4,000 genes and WISH patterns of more than 250 genes, and more than 2,400 annotated WISH images.

Conclusion

Our work provides tissue-specific expression patterns for a large fraction of the sea urchin genes that have not yet been included in existing regulatory networks and await functional integration. Furthermore, we noted neuron-inducing activity of zinc on embryonic development; this is the first observation of such activity in any organism.
Adenosine A2a receptor-mediated, normoxic induction of HIF-1 through PKC and PI-3K-dependent pathways in macrophages
Authors: De Ponti Cristina , Carini Rita , Alchera Elisa , Nitti Maria Paola , Locati Massimo , Albano Emanuele , Cairo Gaetano , Tacchini Lorenza
Published: May 2007

Adenosine released by cells in injurious or hypoxic environments has tissue-protecting and anti-inflammatory effects, which are also a result of modulation of macrophage functions, such as vascular endothelial growth factor (VEGF) production. As VEGF is a well-known target of hypoxia-inducible factor 1 (HIF-1), we hypothesized that adenosine may activate HIF-1 directly. Our studies using subtype-specific adenosine receptor agonists and antagonists showed that by activating the A2A receptor, adenosine treatment induced HIF-1 DNA-binding activity, nuclear accumulation, and transactivation capacity in J774A.1 mouse macrophages. Increased HIF-1 levels were also found in adenosine-treated mouse peritoneal macrophages. The HIF-1 activation induced by the A2A receptor-specific agonist CGS21680 required the PI-3K and protein kinase C pathways but was not mediated by changes in iron levels. Investigation of the molecular basis of HIF-1 activation revealed the involvement of transcriptional and to a larger extent, translational mechanisms. HIF-1 induction triggered the expression of HIF-1 target genes involved in cell survival (aldolase, phosphoglycerate kinase) and VEGF but did not induce inflammation-related genes regulated by HIF-1, such as TNF-α or CXCR4. Our results show that the formation of adenosine and induction of HIF-1, two events which occur in response to hypoxia, are linked directly and suggest that HIF-1 activation through A2A receptors may contribute to the anti-inflammatory and tissue-protecting activity of adenosine.
Loss of Integrity of Thyroid Morphology and Function in Children Born to Mothers with Inadequately Treated Graves’ Disease
Authors: Kempers Marlies J. E. , van Trotsenburg A. S. Paul , van Rijn Rick R. , Smets Anne M. J. B. , Smit Bert J. , de Vijlder Jan J. M. , Vulsma Thomas
Published: May 2007

Context: Central congenital hypothyroidism (CH-C) in neonates born to mothers with inadequately treated Graves’ disease usually needs T4 supplementation. The thyroid and its regulatory system have not yet been extensively studied after T4 withdrawal, until we observed disintegrated thyroid glands in some patients.

Objective: The aim was to study the occurrence and pathogenesis of disintegrated thyroid glands in CH-C patients.

Design, Setting, Patients, Participants: Thyroid function was measured and thyroid ultrasound imaging was performed in 13 children with CH-C due to inadequately treated maternal Graves’ disease after T4-supplementation withdrawal (group Aa). In addition, thyroid ultrasound imaging was performed in six children with CH-C born to inadequately treated mothers with Graves’ disease, in whom T4 supplementation was not withdrawn yet (group Ab) or never initiated (group Ac), in six euthyroid children born to adequately treated mothers with Graves’ disease (group B), and in 10 T4-supplemented children with CH-C as part of multiple pituitary hormone deficiency (group C).

Main Outcome Measures: Thyroid function and aspect (volume, echogenicity, echotexture) were measured.

Results: In group A, five children had developed thyroidal hypothyroidism characterized by persistently elevated TSH concentrations and exaggerated TSH responses after TRH stimulation. In the majority of patients in groups A and C, thyroid echogenicity and volume were decreased, and echotexture was inhomogeneous. Thyroid ultrasound imaging was normal in group B children.

Conclusions: Inadequately treated maternal Graves’ disease not only may lead to CH-C but also carries an, until now, unrecognized risk of thyroid disintegration in the offspring as well. We speculate that insufficient TSH secretion due to excessive maternal-fetal thyroid hormone transfer inhibits physiological growth and development of the child’s thyroid.
Transient Scrotal Hyperthermia and Levonorgestrel Enhance Testosterone-Induced Spermatogenesis Suppression in Men through Increased Germ Cell Apoptosis
Authors: Wang Christina , Cui Yu-Gui , Wang Xing-Hai , Jia Yue , Sinha Hikim Amiya , Lue Yan-He , Tong Jian-Son , Qian Li-Xin , Sha Jia-Hao , Zhou Zuo-Min , Hull Laura , Leung Andrew , Swerdloff Ronald S.
Published: May 2007

Context: In rodents and monkeys, a combination of hormonal and physical agents accelerates germ cell death.

Objective: A “proof of concept” study was performed to investigate whether addition of heat exposure or a progestin to an androgen induces germ cell death and more complete and rapid spermatogenesis suppression.

Design and Settings: A randomized clinical trial was performed at academic medical centers.

Participants: We treated four groups of healthy male volunteers (18 per group) for 18 wk: 1) testosterone undecanoate (TU) 1000 mg im (first dose), followed by 500 mg im every 6 wk; 2) submersion of scrota at 43 C in water for 30 min/d for 6 consecutive days; 3) TU plus heat; and 4) TU plus oral levonorgestrel (LNG) 250 μg/d.

Main Outcome Measures: Semen parameters, testicular histology, and germ cell apoptosis were the main outcome measures.

Results: Heat alone and TU plus heat suppressed sperm counts more than TU alone by wk 6. By wk 9, recovery began in the heat only group, whereas spermatogenesis remained suppressed in the TU plus heat group. Oral LNG plus TU suppressed spermatogenesis earlier and more severely than TU alone. At wk 2, significantly greater germ cell apoptosis occurred in heat and heat plus TU subjects, but not in subjects without heat treatment, compared with pretreatment subjects. By 9 wk, markedly smaller seminiferous tubule diameters and fewer spermatocytes and spermatids were noted in all 12 biopsies from men receiving TU, TU plus LNG, with most dramatic differences for the TU plus heat group, whereas no differences from pretreatment biopsies were observed in men who received heat treatment only.

Conclusions: Heat causes a rapid and transient suppression of spermatogenesis. TU plus heat resulted in low-sperm output that was maintained by continuous treatment with TU. Addition of an oral progestin accelerated spermatogenesis suppression by TU alone. Increased germ cell apoptosis contributed to suppression of spermatogenesis.
Sirtuin 1 Is Required for Antagonist-Induced Transcriptional Repression of Androgen-Responsive Genes by the Androgen Receptor
Authors: Dai Yan , Ngo Duyen , Forman Lora W. , Qin David C. , Jacob Johanna , Faller Douglas V.
Published: May 2007

Androgen antagonists or androgen deprivation is a primary therapeutic modality for the treatment of prostate cancer. Invariably, however, the disease becomes progressive and unresponsive to androgen ablation therapy (hormone refractory). The molecular mechanisms by which the androgen antagonists inhibit prostate cancer proliferation are not fully defined. In this report, we demonstrate that sirtuin 1 (SIRT1), a nicotinamide adenosine dinucleotide-dependent histone deacetylase (HDAC) linked to the regulation of longevity, is required for androgen antagonist-mediated transcriptional repression and growth suppression. Androgen antagonist-bound androgen receptor (AR) recruits SIRT1 and nuclear receptor corepressor to AR-responsive promoters and deacetylates histone H3 locally at the prostate-specific antigen promoter. Furthermore, SIRT1 down-regulation by small interfering RNA or by pharmacological means increased the sensitivity of androgen-responsive genes to androgen stimulation, enhanced the sensitivity of prostate cancer cell proliferative responses to androgens, and decreased the sensitivity of prostate cancer cells to androgen antagonists. In this study, we demonstrate the ligand-dependent recruitment of a class III HDAC into a corepressor transcriptional complex and a necessary functional role for a class III HDAC as a transcriptional corepressor in AR antagonist-induced transcriptional repression. Collectively, these findings identify SIRT1 as a corepressor of AR and elucidate a new molecular pathway relevant to prostate cancer growth and approaches to therapy.
Mapping the Architecture of Secretin Receptors with Intramolecular Fluorescence Resonance Energy Transfer Using Acousto-Optic Tunable Filter-Based Spectral Imaging
Authors: Lisenbee Cayle S. , Harikumar Kaleeckal G. , Miller Laurence J.
Published: May 2007

The molecular structure and agonist-induced conformational changes of class II G protein-coupled receptors are poorly understood. In this work, we developed and characterized a series of dual cyan fluorescent protein (CFP)-tagged and yellow fluorescent protein (YFP)-tagged secretin receptor constructs for use in various functional and fluorescence analyses of receptor structural variants. CFP insertions within the first or second intracellular loop domains of this receptor were tolerated poorly or partially, respectively, in receptors tagged with a carboxyl-terminal yellow fluorescent protein that itself had no effect on secretin binding or cAMP production. A similar CFP insertion into the third intracellular loop resulted in a plasma membrane-localized receptor that bound secretin and signaled normally. This fully active third-loop variant exhibited a significant decrease in fluorescence resonance energy transfer signals that were recorded with an acousto-optic tunable filter microscope after exposure to secretin agonist but not to a receptor antagonist. These data demonstrate changes in the relative positions of intracellular structures that support a model for secretin receptor activation.
China and the World: The Tale of a Topos
Authors: Saussy Haun
Published: May 2007

Haun Saussy is Bird White Housum Professor of Comparative Literature and of East Asian Languages and Literatures at Yale University. His most recent book is the edited collection Comparative Literature in an Age of Globalization (2006). Among his forthcoming projects are a critical edition of the Ernest Fenollosa - Ezra Pound essay “The Chinese Written Character as a Medium for Poetry” and a translation of Jean Métellus's Au pipirite chantant.
The Arabian Nights, Arab-European Literary Influence, and the Lineages of the Novel
Authors: Johnson Rebecca Carol , Maxwell Richard , Trumpener Katie
Published: May 2007

Rebecca Carol Johnson is a doctoral candidate in comparative literature at Yale University. Her research focuses on the development of Arabic and European novels as an inquiry into the global circulation of form. Her interests also include the poetics, politics, and practice of translation. Her translation of Sinan Antoon's novel, I'jaam: An Iraqi Rhapsody, is forthcoming.

Richard Maxwell teaches comparative literature at Yale University. He is author of The Mysteries of Paris and London (1992) and editor of The Victorian Illustrated Book (2002), Charles Dickens's Tale of Two Cities (2003), and, with Katie Trumpener, The Cambridge Companion to Fiction of the Romantic Period (forthcoming). He is working on a study of historical fiction from 1660 to the present. His essay “Pretenders in Sanctuary” appeared in the June 2000 issue of MLQ.

Katie Trumpener is professor of comparative literature and English at Yale University. Her first book, Bardic Nationalism: The Romantic Novel and the British Empire (1997), surveys the novel's rise in Ireland, Scotland, and the early British Empire. A forthcoming book compares the East and West German cinemas. Her current book project is a comparative study of European modernism.
Traveling Poetry
Authors: Ramazani Jahan
Published: May 2007

Jahan Ramazani, Edgar F. Shannon Professor of English and department chair at the University of Virginia, is author of Poetry of Mourning: The Modern Elegy from Hardy to Heaney (1994) and The Hybrid Muse: Postcolonial Poetry in English (2001), among other works. He is also coeditor of The Norton Anthology of Modern and Contemporary Poetry (2003) and “The Twentieth Century and After” in The Norton Anthology of English Literature (2006).
Anti-anti: Utopia, Globalization, Jameson
Authors: Cazdyn Eric
Published: May 2007

Eric Cazdyn is associate professor of comparative literature and East Asian studies at the University of Toronto. He is guest editor of a forthcoming issue of South Atlantic Quarterly on the political and philosophical consequences of disaster, and he is finishing a manuscript on illness and globalization. His book The Flash of Capital: Film and Geopolitics in Japan appeared in 2002.
Cerberus is a feedback inhibitor of Nodal asymmetric signaling in the chick embryo
Authors: Tavares Ana Teresa , Andrade Sofia , Silva Ana Cristina , Belo José António
Published: May 2007

The TGF-β-related molecule Nodal plays an essential and conserved role in left-right patterning of the vertebrate embryo. Previous reports have shown that the zebrafish and mouse Cerberus-related proteins Charon and Cerberus-like-2 (Cerl-2), respectively, act in the node region to prevent the Nodal signal from crossing to the right side, whereas chick Cerberus (cCer)has an unclear function in the left-side mesoderm. In this study, we investigate the transcriptional regulation and function of cCer in left-right development. By analyzing the enhancer activity of cCer 5′genomic sequences in electroporated chick embryos, we identified a cCer left-side enhancer that contains two FoxH1 and one SMAD binding site. We show that these Nodal-responsive elements are necessary and sufficient for the activation of transcription in the left-side mesoderm. In transgenic mouse embryos, cCer regulatory sequences behave as in chick embryos, suggesting that the cis-regulatory sequences of Cerberus-related genes have diverged during vertebrate evolution. Moreover, our findings from cCer overexpression and knockdown experiments indicate that cCer is a negative-feedback regulator of Nodal asymmetric signaling. We propose that cCer and mouse Cerl-2 have evolved distinct regulatory mechanisms but retained a conserved function in left-right development, which is to restrict Nodal activity to the left side of the embryo.
Stem cells and their niche: an inseparable relationship
Authors: Xie Ting , Li Linheng
Published: May 2007

A recent Keystone symposium on `Stem Cell Interactions with their Microenvironmental Niche' was organized by David T. Scadden and Allan C. Spradling. The meeting was held in conjunction with another Keystone symposium, `Stem Cells and Cancer', at Keystone, Colorado. Among the work that was presented at this meeting, scientists presented data that advances our understanding of the contribution that the niche makes to stem cell maintenance. Novel types of stem cells and niches were also reported and new findings that clarify our understanding of the molecular mechanisms that regulate and maintain stem cells were presented.
Regulation of ventral midbrain patterning by Hedgehog signaling
Authors: Bayly Roy D. , Ngo Minhtran , Aglyamova Galina V. , Agarwala Seema
Published: May 2007

In the developing ventral midbrain, the signaling molecule sonic hedgehog(SHH) is sufficient to specify a striped pattern of cell fates (midbrain arcs). Here, we asked whether and precisely how hedgehog (HH) signaling might be necessary for ventral midbrain patterning. By blocking HH signaling by in ovo misexpression of Ptc1Δloop2,we show that HH signaling is necessary and can act directly at a distance to specify midbrain cell fates. Ventral midbrain progenitors extinguish their dependence upon HH in a spatiotemporally complex manner, completing cell-fate specification at the periphery by Hamburger and Hamilton stage 13. Thus,patterning at the lateral periphery of the ventral midbrain is accomplished early, when the midbrain is small and the HH signal needs to travel relatively short distances (approximately 30 cell diameters). Interestingly, single-cell injections demonstrate that patterning in the midbrain occurs within the context of cortex-like radial columns of cells that can share HH blockade and are cytoplasmically connected by gap junctions. HH blockade results in increased cell scatter, disrupting the spatial coherence of the midbrain arc pattern. Finally, HH signaling is required for the integrity and the signaling properties of the boundaries of the midbrain (e.g. the midbrain-hindbrain boundary, the dorsoventral boundary), its perturbations resulting in abnormal cell mixing across `leaky' borders.
Inhibition of complex III promotes loss of Ca2+ dependence for mitochondrial superoxide formation and permeability transition evoked by peroxynitrite
Authors: Guidarelli Andrea , Cerioni Liana , Cantoni Orazio
Published: May 2007

In intact U937 cells, peroxynitrite promotes the mitochondrial formation of superoxide via a Ca2+-dependent mechanism involving inhibition of complex III. Superoxide then readily dismutates to H2O2 causing lesions on different biomolecules, including DNA. Here we show that formation of H2O2 and DNA damage are suppressed by inhibition of complex I (by rotenone) or ubisemiquinone formation (by myxothiazol), as well as by a variety of manipulations preventing either the mobilization of Ca2+ or its mitochondrial accumulation. In addition, complex III inhibitors promoted rotenone- or myxothiazol-sensitive formation of H2O2 and DNA strand scission in cells exposed to otherwise inactive concentrations of peroxynitrite. However, under these conditions, the intra-mitochondrial concentration of Ca2+ remained unchanged and the effects of peroxynitrite therefore take place via Ca2+-independent mechanisms. H2O2 formation was paralleled by, and causally linked to, the loss of mitochondrial membrane potential associated with the mitochondrial release of cytochrome c and AIF, and with the mitochondrial accumulation of Bax. These events, although Ca2+ independent, were rapidly followed by death mediated by mitochondrial permeability transition, generally considered a typical Ca2+-dependent event. Thus, enforced inhibition of complex III promotes the loss of Ca2+ dependence of those mitochondrial mechanisms regulating superoxide formation and mitochondrial permeability transition evoked by peroxynitrite.
Dynamic cofilin phosphorylation in the control of lamellipodial actin homeostasis
Authors: Jovceva Eleonora , Larsen Martin R. , Waterfield Michael D. , Baum Buzz , Timms John F.
Published: May 2007

During animal cell chemotaxis, signalling at the plasma membrane induces actin polymerisation to drive forward cell movement. Since the cellular pool of actin is limited, efficient protrusion formation also requires the coordinated disassembly of pre-existing actin filaments. To search for proteins that can monitor filamentous and globular actin levels to maintain the balance of polymerisation and disassembly, we followed changes in the proteome induced by RNA interference (RNAi)-mediated alterations in actin signalling. This unbiased approach revealed an increase in the levels of an inactive, phosphorylated form of the actin-severing protein cofilin in cells unable to generate actin-based lamellipodia. Conversely, an increase in F-actin levels induced the dephosphorylation and activation of cofilin via activation of the Ssh phosphatase. Similarly, in the context of acute phosphoinositide 3-kinase (PI3K) signalling, dynamic changes in cofilin phosphorylation were found to depend on the Ssh phosphatase and on changes in lamellipodial F-actin. These results indicate that changes in the extent of cofilin phosphorylation are regulated by Ssh in response to changes in the levels and/or organisation of F-actin. Together with the recent finding that Ssh phosphatase activity is augmented by F-actin binding, these results identify Ssh-dependent regulation of phosphorylated cofilin levels as an important feedback control mechanism that maintains actin filament homeostasis during actin signalling.
The atypical Rho family GTPase Wrch-1 regulates focal adhesion formation and cell migration
Authors: Chuang Ya-yu , Valster Aline , Coniglio Salvatore J. , Backer Jonathan M. , Symons Marc
Published: May 2007

Wrch-1 (Wnt-regulated Cdc42 homolog) is a new member of the Rho family that was identified as a gene transcriptionally upregulated by Wnt-1. Wrch-1 has no detectable GTPase activity and displays very high intrinsic guanine nucleotide exchange, implying that it is constitutively GTP-bound. The biological functions of Wrch-1 largely remain to be characterized. Here, we report that Wrch-1 prominently localizes to focal adhesions. Depletion of Wrch-1 by small interfering RNA increases focal adhesion formation, whereas Wrch-1 overexpression disassembles focal adhesions. Wrch-1 depletion inhibits myosin-light-chain phosphorylation, which in turn leads to an increase in the number of focal adhesions and inhibits cell migration in response to wound healing. Depletion of Wrch-1 also inhibits Akt and JNK activation. Although pharmacological inhibitors of Akt and JNK inhibit cell migration, they do not affect focal adhesions. Thus, our data suggest that Wrch-1 regulates cell migration by multiple mechanisms: on the one hand Wrch-1 controls focal adhesions by regulating myosin light chain and on the other hand Wrch-1 stimulates the activation of Akt and JNK.
Induced Amnesia for Distressing Information in a Nonclinical Sample
Authors: Moulds Michelle L. , Bryant Richard A.
Published: May 2007

Dissociative reactions during and subsequent to traumatic events are theorised to result in memory deficits for trauma-related information. This study investigated the interaction between induced amnesia and dissociative reactions. Participants (N = 29) were presented with a word list, a series of disfigured or neutral faces and a second word list, followed by free recall and recognition tasks. Participants presented with disfigured faces recalled fewer words from the postimage list in the free recall task than those presented with neutral faces; however, there were no between-group differences for recognition. No relationship was observed between dissociative tendencies and memory performance. Trait dissociation was unrelated to induced amnesia effects. Findings are interpreted in terms of impaired consolidation of information following encoding of distressing information. Implications of the results for the clinical management of traumatized individuals are considered.
A Fast, Reciprocal Pathway between the Lateral Geniculate Nucleus and Visual Cortex in the Macaque Monkey
Authors: Briggs Farran , Usrey W. Martin
Published: May 2007

Neurons in the lateral geniculate nucleus (LGN) not only provide feedforward input to primary visual cortex (V1), but also receive robust feedback from the cortex. Accordingly, visual processing in the LGN is continuously influenced by previous patterns of activity. This study examines the temporal properties of feedforward and feedback pathways between the LGN and V1 in the macaque monkey to provide a lower bound on how quickly the cortex can influence the LGN. In so doing, we identified a subclass of corticogeniculate neurons that receives direct, suprathreshold input from the LGN that is similar in latency to that directed to other recipient neurons (4.2 ± 0.4 vs 4.0 ± 0.2 ms). These neurons also provide feedback to the LGN that is significantly shorter in latency than that supplied by corticogeniculate neurons lacking LGN input (5.1 ± 1.3 vs 11.1 ± 2.3 ms, respectively). Across our sample of corticogeniculate neurons, the shortest combined visual response latency and feedback latency was 37 ms (mean, 52.5 ± 3.8 ms), indicating that visual signals can rapidly travel from the periphery to the cortex and back to the LGN.
Prolonged Glial Expression of Sox4 in the CNS Leads to Architectural Cerebellar Defects and Ataxia
Authors: Hoser Melanie , Baader Stephan L. , Bösl Michael R. , Ihmer Alice , Wegner Michael , Sock Elisabeth
Published: May 2007

Sox proteins of group C are strongly expressed in the developing nervous system and have been associated with maturation of neurons and glia. Here, we overexpressed the group C protein Sox4 in transgenic mice under the control of the human GFAP promoter. Transgene expression was detected in radial glia and astrocytes throughout the CNS. The transgenic mice were ataxic and exhibited hydrocephaly as well as cerebellar malformations. In the cerebellum, fissures were not formed and neuronal layering was dramatically disturbed. Nevertheless, all neuronal cell types of the cerebellum were present as well as cells with characteristics of early radial glia, astrocytes, and oligodendrocytes. However, radial glia failed to migrate into the position normally taken by Bergmann glia and did not extend radial fibers toward the pial surface. The cerebellar malformations can therefore be explained by the absence of functional Bergmann glia. We conclude that Sox4 expression counteracts differentiation of radial glia and has to be downregulated before full maturation can occur.
Zic1andZic3Regulate Medial Forebrain Development through Expansion of Neuronal Progenitors
Authors: Inoue Takashi , Ota Maya , Ogawa Miyuki , Mikoshiba Katsuhiko , Aruga Jun
Published: May 2007

The medial telencephalon is a source of neurons that follow distinct tangential trajectories of migration to various structures such as the cerebral cortex, striatum, and olfactory bulb. In the present study, we characterized the forebrain anomalies inZic1/Zic3compound mutant mice.Zic1andZic3were strongly expressed in the medial structures, including the septum, medial cerebral cortex, and choroid plexus. Mice homozygous for theZic1mutant allele together with the nullZic3allele showed medial forebrain defects, which were not obvious in eitherZic1orZic3single mutants. Absence of bothZic1andZic3caused hypoplasia of the hippocampus, septum, and olfactory bulb. Analysis of the cell cycle revealed that the cell cycle exit rate was increased in the septa of double mutants. Misexpression of Zic3 in the ventricular layer of the cerebral cortex inhibited neuronal differentiation. These results indicated that bothZic1andZic3function in maintaining neural precursor cells in an undifferentiated state. The functions of these genes may be essential to increasing neural cell numbers regionally in the medial telencephalon and to proper mediolateral patterning of the telencephalon.
Die Macht des Lebens und die Freiheit zum Tod. Spinozas Theorie des Suizids im Problemfeld moderner Subjektivität
Authors: Sandkaulen Birgit
Published: May 2007

Die Auseinandersetzung um die Problematik des Suizids ist üblicherweise an den Kategorien von Recht und Unrecht orientiert. Ausgehend von Spinozas Ontologie der Macht, die Selbsttötung als unmöglich ausschließt, wird die Debatte hier in die Frage nach einem ursprünglichen Können der Negation der Selbsterhaltung verschoben. Dies erlaubt, sowohl den Zwiespalt der Medizin zwischen Autonomie oder Pathologie der suizidalen Handlung als auch das exemplarische Suizidverbot bei Kant und Hegel kritisch zu durchleuchten und die moralische Konfliktdimension der Selbsttötung am Ende einer neuen Einschätzung zuzuführen.
Kidnapping Public Schooling: Perversion and Normalization of the Discursive Bases within the Epicenter of New Right Educational Policies
Authors: Paraskeva João M.
Published: May 2007

Public schooling has been kidnapped. The author examines how this happened – since we all know very well who did it. How did public schooling become a hostage of world's neo-rightist political processes? This article attempts to unveil some of those strategies that underpin the very core of the neo-rightist current triumphalistic posture. To understand the way neo-rightist political processes encompassed public schooling at such a frightening pace it is necessary to situate neoliberal policies based on what has been called the third hegemony of historical capitalism. Also it is necessary to be aware of (a) how particular key concepts and practices have been cleverly and gradually twisted and perverted, positively hijacked from the social sphere, and coined within an economic flavoured materiality, and (b) how the new rightist triumphalism is deeply enmeshed within the politics of the common sense and the role that the media plays in building a particular commonsensical framework. The article ends by taking the Portuguese reality as an example, not only denouncing the poor record of some of the graduate and teaching education courses within the universities and colleges, but stating the need to rescue democracy by reinventing it.
Neoliberalism and the World Bank: Economic Discourse and the (re)Production of Gendered Identity(ies)
Authors: Griffin Penny
Published: May 2007

This article examines the World Bank's discourse of neoliberalism with a view to understanding how this informs and sustains the Bank's policies and practices in particularly gendered ways. ‘Neoliberalism’ is, here, a discursive structure that constitutes a powerful and pervasive contemporary model of economic development, resting on assumptions of economic growth and stability, financial transactions and human behaviour that are deeply gendered whilst presented as universal and neutral. The article thus seeks to offer an analysis of the discursive practices by which the Bank (re)produces a fundamentally gendered discourse of neoliberalism. Neoliberal discourse is a power-laden and discursively regulatory framework of economic identity that (re)produces the social reality that it defines through particular discursive practices, predicating, pre/proscribing and (re)producing the meanings, behaviours and human identities that best correspond with the pre-given, economic ‘reality’ thereby constructed. It is in the places that the Bank does not explicitly discuss or mention gender that gender identity(ies) most clearly reside, constituting the foundations of the Bank's neoliberal economic logic and informing at every level the Bank's processes of decision and policy making.
Oral Antidiabetic Drugs in Pregnancy: The Other Alternative
Authors: Langer Oded
Published: May 2007

The use of oral antidiabetic drugs in pregnancy is an accepted treatment modality for women with gestational diabetes mellitus (GDM). This efficacious option provides physicians more choices that, in turn, translate into more complex decision making for the management of GDM. However, regardless of the mode of therapy, whole patient care (glucose monitoring, education, diet adherence, and so forth) will determine overall success in managing this disease and the potential to maximize the quality of perinatal outcome.
A Combined, Minimally Invasive Transnasal Approach to the Sella Turcica
Authors: Nasseri Shawn S. , McCaffrey Thomas V. , Kasperbauer Jan L. , Atkinson John L.
Published: May 2007

The increasing use of endonasal techniques and a new 3-dimensional CT-guided imaging system have allowed us to develop a combined, minimally invasive endonasal approach to the pituitary gland. Thus far, more than 30 patients have undergone an endonasal transsphenoidal approach to the sella using a combined endoscopic approach, with additional selective use of the Instatrak CT-guided imaging system for realtime imaging. Our current technique involves obtaining a preoperative CT using a plastic head frame with registration markers. By using this head frame intraoperatively, real-time localization with CT images in axial, coronal, and sagittal planes can be performed. Using endoscopic techniques and a Papavero-Caspar speculum, the sella is exposed. A combined approach using endoscopes, the operating microscope, and real-time localization is undertaken to expose and resect tumors. We have encountered minimal associated complications in our series, and this method has been progressively modified to improve exposure and safety. Because we are able to visualize the sella without a sublabial incision or septal resection, we have nearly eliminated the need for nasal packing, reduced the average hospital stay to 2.5 days, and improved patient satisfaction.
Ipratropium Bromide Nasal Spray 0.03% Provides Additional Relief from Rhinorrhea When Combined With Terfenadine in Perennial Rhinitis Patients; A Randomized, Double-Blind, Active-Controlled Trial
Authors: Finn Albert F. , Aaronson Donald , Korenblat Phillip , Lumry William , Settipane Guy , Spector Sheldon , Woehler Thomas , Drda Kristin , Wood Chester C.
Published: May 2007

Medical treatment of perennial rhinitis is aimed at providing symptomatic relief of individual symptoms. Multiple agents are administered when no single agent provides complete relief. Studies assessing the benefit/risk of combined therapy are important, especially for newly available agents such as ipratropium bromide nasal spray, a topical anticholinergic agent approved for the treatment of rhinorrhea in allergic and nonallergic perennial rhinitis. The objective was to determine whether the combined use of ipratropium bromide nasal spray 0.03% (42 mcg per nostril) administered three times daily with a nonsedating antihistamine (terfenadine, 60 mg administered twice daily) is safe and provides greater clinical benefit than use of the placebo nasal spray plus terfenadine. Our method was a multicenter, 6-week, double-blind, randomized, active-controlled, crossover trial of 205 patients with perennial rhinitis (114 allergic and 91 nonallergic), 18 to 75 years of age, who had clinically significant rhinorrhea. After a 1-week run-in period, patients were treated for 2 weeks with one of the two treatment regimens, followed by a 1-week washout period, and then were treated for another 2 weeks with the other treatment regimen. Daily diary symptoms scores of rhinorrhea, congestion, and sneezing were obtained, as well as biweekly patient and physician global assessments of treatment effectiveness of each of the nasal symptoms. Ipratropium bromide nasal spray plus terfenadine was more effective than vehicle plus terfenadine in reducing the average severity (38% versus 28%) and duration (46% versus 30%) of rhinorrhea during the 2 weeks of treatment from baseline (p < 0.05). The advantage of ipratropium bromide nasal spray plus terfenadine was evident by the second day of treatment and continued throughout the 2-week treatment period. Of patients who responded more to one treatment than another, 69% responded to ipratropium bromide nasal spray plus terfenadine, compared to 31% to vehicle plus terfenadine (p < 0.05). Both physicians and patients rated control of rhinorrhea and sneezing by ipratropium bromide nasal spray plus terfenadine as superior to vehicle plus terfenadine (p < 0.05). The symptom of congestion was controlled equally well by both treatments. Combined active therapy was well tolerated with no increase in adverse events over that seen previously with ipratropium bromide nasal spray alone. The combination of ipratropium bromide nasal spray with terfenadine is more effective than vehicle plus terfenadine for the treatment of rhinorrhea, and does not result in a potentiation of adverse drug reactions.
Video-Endoscope versus Endoscope for Paranasal Sinus Surgery: Influence on Stereoacuity
Authors: Tasman Abel-Jan , Stammberger Heinz
Published: May 2007

A matter of debate is whether the use of a video-endoscope impairs visual orientation and manual precision in endonasal surgery. We investigated the influence of video-endoscopy compared to endoscopy on stereoacuity in a model of the nasal cavity. Twenty medical staff members were asked to touch defined points in a spatial model of the nasal cavity as quickly as possible and in correct order using 0° and 30° endoscopes, looking directly through the endoscope or looking at a video monitor connected to a CCD camera on the endoscope. Time, number of omissions of points and faults in point sequence were recorded. Manipulations were significantly quicker when the “operative field” was seen directly through the endoscope compared to orientation from the monitor for both 0° endoscope 96 ± 4.7 s. vs. 108 ± 5.6 s. and 30° endoscope 84 ± 3.9 s. vs. 96 ± 5.5 s. (±SEM). There was no difference in number of omissions and faults in sequence between “endoscope” and “video-endoscope.” The fact that the use of a video-endoscope did not increase the number of faults in our experiment does not support the notion that performing endoscopic sinus surgery using a monitor is unsafe. In the hands of the participants who were experienced with the endoscope, however, the use of a video-endoscope slowed down manipulations to a significant degree. To which extent this may be due to the effect of training or to superiority of the endoscope per se will remain a matter of discussion until a group of experienced video-endoscopists will have repeated the study.
Clarithromycin Suppresses Proliferation of Rat Nasal Epithelium Exposed to Endotoxin
Authors: Tohnai Akira , Hashiba Motoyuki , Baba Shunkichi
Published: May 2007

A study was performed to elucidate the action of long-term macrolide therapy in chronic sinusitis. Clarithromycin (CAM) was administered orally once daily for 14 days. On the last 3 days, an endotoxin, lipopolysaccharide (LPS) was instilled intranasally. The extent of DNA synthesis acceleration was studied in both controls and pretreated animals by counting the number of 5-bromo-2′-deoxyuridine (BrdU)-labeled cells in the nasal transitional epithelium. Six hours after the final intranasal instillation of LPS, the number of BrdU-positive cells was significantly higher than control. Pretreatment with CAM for 2 weeks significantly inhibited this increase. Because similar results were obtained in neutrophil-depleted rats, LPS apparently promotes proliferation of the nasal epithelium in the absence of neutrophils; CAM-suppressed epithelial proliferation independently of the neutrophil count. Our results suggest that CAM inhibits LPS-induced increased rates of DNA synthesis by directly affecting the nasal epithelium. The mechanism by which macrolide therapy alleviates the signs and symptoms of chronic sinusitis might therefore involve suppression of inflammatory processes in the nasal and paranasal sinus epithelium.
The Effect of Ankle Position on the Static Tension in the Achilles Tendon Before and After Operative Repair: A Biomechanical Cadaver Study
Authors: Labib Sameh , Hage William D. , Sutton Karen Michelle , Hutton William
Published: May 2007

Background: We hypothesized that there no need to position the foot in plantarflexion after operative repair of an Achilles tendon rupture. Methods: In five fresh cadaver lower extremity specimens, the static tension in the Achilles tendon was measured as the ankle was sequentially dorsiflexed from 30, to 20, to 10, to 0 degrees of plantarflexion. The tendon was then transected and repaired using a modified Krakow locking loop suture technique. The tension in the tendon was again measured as the foot was sequentially dorsiflexed through the same range of motion: 30, to 20, to 10, to 0 degrees. The repair was then tensile tested to failure. Results: The intact Achilles tendons generated on average 10 N, 10 N, 15.8 N and 31.9.0 N of tension at 30, 20, 10, and 0 degrees of plantarflexion, respectively. After a modified Krakow locking loop repair, the tension across the repair site was 10 N, 11.46 N, 18.4 N, and 30.3 N at 30, 20, 10, and 0 degrees of plantarflexion. Thus, moving the ankle from 30 degrees to neutral placed an additional force of 21.9 N on the intact tendon and 20.3 N on the repaired tendon. The mean tensile strength of the modified Krakow repair was 598.6 N (range 167 1129 N). Conclusions: The tension in the repaired tendon at neutral position is only a small percentage (6.4%) of the strength of the tendon when operatively repaired by a modified Krakow locking loop suture technique. Clinical Relevance: Our results suggest that the ankle joint does not have to be positioned in plantarflexion after operative repair using the described technique.
Correlation of the AOFAS Scores with a Generic Health Qualy Score in Foot and Ankle Surgery
Authors: Malviya Ajay , Makwana Nilesh , Laing Patrick
Published: May 2007

Background: The American Orthopaedic Foot and Ankle Score (AOFAS) is one scoring system used to assess and monitor the progress of patients after foot and ankle surgery. The aim of this study was to evaluate the trend of the AOFAS score over a period of time and correlate it with the QUALY score, which is a valid and reliable scoring system. Methods: All patients undergoing surgery by one foot and ankle surgeon between January, 2001, and July, 2003, were reviewed. The preoperative AOFAS and QUALY and postoperative scores at 3, 6 and 12 months, and yearly were collected prospectively. Results: This study includes 204 operative procedures in 159 patients. The mean age of the patients was 51.9 (range 12 to 89) years. The AOFAS scores increased from a mean of 45.5 preoperatively to 76.5 at 3 months and reached a peak of 81.5 at 6 months and then started to decrease to 79.2 at 12 months. This fall, though seemingly marginal, was significant ( p < 0. 01). This trend seems to be consistent for all the procedures. The 6-month AOFAS score was found to have a higher correlation with the final QUALY score ( r 2 = 0.423) than the 12-month AOFAS score ( r 2 = 0.326). Conclusions: The AOFAS score has low levels of correlation with the validated generic health QUALY score. Our study suggests that scores collected preoperatively, at 6 and 12 months after surgery, and annually there after may be best. The 3-month score may not be necessary. We recommend that a generic health score such as the QUALY score be used in conjunction with the AOFAS score to reflect outcome.