bluuebunny/crossref_metadata_2025 huggingface dataset:
Central Roles of the Roof Plate in Telencephalic Development and Holoprosencephaly
Authors: Cheng Xun , Hsu Ching-mei , Currle D. Spencer , Hu Jia Sheng , Barkovich A. James , Monuki Edwin S.
Published: July 2006

The roof plate is a well known signaling center in CNS development, but its roles in the developing telencephalon and the common holoprosencephaly (HPE) malformation have been uncertain. Using cellular ablations in mice, we show that roof plate cell loss causes failed midline induction and HPE in the dorsal telencephalon. This morphologic phenotype is accompanied by selective deficits in midline gene expression and a reduced activity gradient for bone morphogenetic proteins (Bmps), the major signals produced by the roof plate. In dissociated cells and mutant explants, exogenous Bmp4 is sufficient to mimic roof plate selectivity in midline gene regulation and to rescue roof plate-dependent midline patterning. Previously unrecognized neuroanatomical defects predicted by the mouse model are then confirmed in human HPE patients. These findings establish selective roles for roof plate-dependent Bmp signaling in dorsal telencephalic patterning and HPE and define novel candidate genes for the human disorder.
Polyglutamine Proteins at the Pathogenic Threshold Display Neuron-Specific Aggregation in a Pan-NeuronalCaenorhabditis elegansModel
Authors: Brignull Heather R. , Moore Finola E. , Tang Stephanie J. , Morimoto Richard I.
Published: July 2006

The basis of neuron-specific pathogenesis, resulting from the expression of misfolded proteins, is poorly understood and of central importance to an understanding of the cell-type specificity of neurodegenerative disease. In this study, we developed a new model for neuron-specific polyQ pathogenesis inCaenorhabditis elegansby pan-neuronal expression that exhibits polyQ length-dependent aggregation, neurotoxicity, and a pathogenic threshold at a length of 35–40 glutamines. Analysis of specific neurons inC. elegansrevealed that only at the threshold length, but not at shorter or longer lengths, polyQ proteins can exist in a soluble state in certain lateral neurons or in an aggregated state in motor neurons of the same animal. These results provide direct experimental evidence that the expression of a single species of a toxic misfolded protein can exhibit a range of neuronal consequences.
Involvement of the Anterior Cingulate Cortex in the Expression of Remote Spatial Memory
Authors: Teixeira Cátia M. , Pomedli Stephen R. , Maei Hamid R. , Kee Nohjin , Frankland Paul W.
Published: July 2006

Although the hippocampus plays a crucial role in the formation of spatial memories, as these memories mature they may become additionally (or even exclusively) dependent on extrahippocampal structures. However, the identity of these extrahippocampal structures that support remote spatial memory is currently not known. Using a Morris water-maze task, we show that the anterior cingulate cortex (ACC) plays a key role in the expression of remote spatial memories in mice. To first evaluate whether the ACC is activated after the recall of spatial memory, we examined the expression of the immediate early gene,c-fos, in the ACC. Fos expression was elevated after expression of a remote (1 month old), but not recent (1 d old), water-maze memory, suggesting that ACC plays an increasingly important role as a function of time. Consistent with the gene expression data, targeted pharmacological inactivation of the ACC with the sodium channel blocker lidocaine blocked expression of remote, but spared recent, spatial memory. In contrast, inactivation of the dorsal hippocampus disrupted expression of spatial memory, regardless of its age. We further showed that inactivation of the ACC blocked expression of remote spatial memory in two different mouse strains, after training with either a hidden or visible platform in a constant location, and using the AMPA receptor antagonist CNQX. Together, our data provide evidence that circuits supporting spatial memory are reorganized in a time-dependent manner, and establish that activity in neurons intrinsic to the ACC is critical for processing remote spatial memories.
Interdomain Interactions in AMPA and Kainate Receptors Regulate Affinity for Glutamate
Authors: Weston Matthew C. , Gertler Christoph , Mayer Mark L. , Rosenmund Christian
Published: July 2006

Ionotropic glutamate receptors perform diverse functions in the nervous system. As a result, multiple receptor subtypes have evolved with different kinetics, ion permeability, expression patterns, and regulation by second messengers. Kainate receptors show slower recovery from desensitization and have different affinities for agonists than AMPA receptors. Based on analysis of ligand binding domain crystal structures, we identified interdomain interactions in the agonist-bound state that are conserved in kainate receptors and absent in AMPA receptors. Mutations in GluR6 designed to disrupt these contacts reduced agonist apparent affinity, speeded up receptor deactivation and increased the rate of recovery from desensitization. Conversely, introduction of mutations in GluR2 that enabled additional interdomain interactions in the agonist-bound state increased agonist apparent affinity 15-fold, and slowed both deactivation and recovery from desensitization. We conclude that interdomain interactions have evolved as a distinct mechanism that contributes to the unique kinetic properties of AMPA and kainate receptors.
Interaction of Survival and Death Signaling in Basal Forebrain Neurons: Roles of Neurotrophins and Proneurotrophins
Authors: Volosin Marta , Song Wenyu , Almeida Ramiro D. , Kaplan David R. , Hempstead Barbara L. , Friedman Wilma J.
Published: July 2006

Proneurotrophins bind with high affinity to p75 neurotrophin receptor (p75NTR) and lack the capacity to bind Trk receptors, suggesting that proneurotrophins can elicit apoptosis via p75NTReven in cells expressing survival-promoting Trk receptors. In the CNS, basal forebrain (BF) neurons are particularly vulnerable to degeneration in Alzheimer’s disease, and are among the few populations of brain neurons that express p75NTRthroughout life. These neurons also express Trk receptors and may be concomitantly exposed to both proneurotrophins and mature neurotrophins during development, disease, or after injury. We investigated the interaction of mature and proneurotrophin signaling in these CNS neurons. Kainic acid-induced seizures elicited production of pro-NGF by BF astrocytes before caspase activation in p75NTR-positive BF neurons, demonstrating local production of proneurotrophins under pathological conditions and suggesting apoptotic signalingin vivo. Mechanisms of proneurotrophin-induced death were analyzed in cultured BF neurons, and required both p75NTRand its coreceptor sortilin. Surprisingly, exposure to both mature neurotrophins and proneurotrophins demonstrated that Trk phosphorylation did not prevent pro-NGF-induced apoptosis via p75NTR. However, activation of PI3K (phosphatidylinositol 3-kinase)/Akt and MEK (mitogen-activated protein kinase kinase)/Erk pathways prevented pro-NGF-induced apoptosis, revealing a novel critical checkpoint in survival versus apoptotic signaling downstream of Trk activation, and suggesting that pro-NGF blocks survival signaling by preventing Akt and Erk activation. This study shows that proneurotrophins are produced in the brain under pathological conditions, and can elicit apoptosis of BF neurons even when Trk receptors are activated.
Responses to Affective Stimuli in Monkeys with Entorhinal or Perirhinal Cortex Lesions
Authors: Meunier Martine , Cirilli Laetitia , Bachevalier Jocelyne
Published: July 2006

Recent efforts to define the functions of the primate rhinal (entorhinal and perirhinal) cortical areas have focused on their interaction with the hippocampus in the mediation of normal memory. Less is known on the functional meaning of their strong connections to the amygdala, a key substrate for emotion. A previous study (Meunier and Bachevalier, 2002) showed evidence that complete rhinal ablations yield changes in monkeys' behavioral responses to affectively salient stimuli. Here, we studied monkeys with separate entorhinal or perirhinal ablations in the same paradigm, where responses were triggered by four stimuli: an unfamiliar human, a conspecific stimulus, a toy snake, and a familiar (generally rewarded) junk object. The two separate lesions produced similar changes, and each replicated the effects of complete rhinal lesions (i.e., attenuated affiliation and enhanced defense). Failure to modulate responses based on previous experience (i.e., memory difficulties) may explain these affective changes. This interpretation does not account, however, for the sparing of some memory-dependent modulations of defense, nor for the lack of correlation between the animals' affective changes and their own recognition memory performance. Alternatively, rhinal damage may introduce a negative bias in the risk assessment of affectively salient stimuli, a proposal more compatible with Gray and McNaughton's (2000) anxiety-centered view of medial temporal functions, than with prominent mnemonic/perceptual functional models of the hippocampal/rhinal duo. Reconciling the two perspectives may improve our understanding of rhinal functions.
Terminal Nerve-Derived Neuropeptide Y Modulates Physiological Responses in the Olfactory Epithelium of Hungry Axolotls (Ambystoma mexicanum)
Authors: Mousley Angela , Polese Gianluca , Marks Nikki J. , Eisthen Heather L.
Published: July 2006

The vertebrate brain actively regulates incoming sensory information, effectively filtering input and focusing attention toward environmental stimuli that are most relevant to the animal's behavioral context or physiological state. Such centrifugal modulation has been shown to play an important role in processing in the retina and cochlea, but has received relatively little attention in olfaction. The terminal nerve, a cranial nerve that extends underneath the lamina propria surrounding the olfactory epithelium, displays anatomical and neurochemical characteristics that suggest that it modulates activity in the olfactory epithelium. Using immunocytochemical techniques, we demonstrate that neuropeptide Y (NPY) is abundantly present in the terminal nerve in the axolotl (Ambystoma mexicanum), an aquatic salamander. Because NPY plays an important role in regulating appetite and hunger in many vertebrates, we investigated the possibility that NPY modulates activity in the olfactory epithelium in relation to the animal's hunger level. We therefore characterized the full-length NPY gene from axolotls to enable synthesis of authentic axolotl NPY for use in electrophysiological experiments. We find that axolotl NPY modulates olfactory epithelial responses evoked byl-glutamic acid, a food-related odorant, but only in hungry animals. Similarly, whole-cell patch-clamp recordings demonstrate that bath application of axolotl NPY enhances the magnitude of a tetrodotoxin-sensitive inward current, but only in hungry animals. These results suggest that expression or activity of NPY receptors in the olfactory epithelium may change with hunger level, and that terminal nerve-derived peptides modulate activity in the olfactory epithelium in response to an animal's changing behavioral and physiological circumstances.
Analysis of the Ataxia Telangiectasia Mutated-Mediated DNA Damage Response in Murine Cerebellar Neurons
Authors: Dar Inbal , Biton Sharon , Shiloh Yosef , Barzilai Ari
Published: July 2006

The DNA damage response is a network of signaling pathways that affects many aspects of cellular metabolism after the induction of DNA damage. The primary transducer of the cellular response to the double-strand break, a highly cytotoxic DNA lesion, is the nuclear protein kinase ataxia telangiectasia (A-T) mutated (ATM), which phosphorylates numerous effectors that play key roles in the damage response pathways. Loss or inactivation of ATM leads to A-T, an autosomal recessive disorder characterized by neuronal degeneration, particularly the loss of cerebellar granule and Purkinje cells, immunodeficiency, genomic instability, radiosensitivity, and cancer predisposition. The reason for the cerebellar degeneration in A-T is not clear. It has been ascribed by several investigators to cytoplasmic functions of ATM that may not be relevant to the DNA damage response. We set out to examine the subcellular localization of ATM and characterize the ATM-mediated damage response in mouse cerebellar neurons. We found that ATM is essentially nuclear in these cells and that various readouts of the ATM-mediated damage response are similar to those seen in commonly used cell lines. These include the autophosphorylation of ATM, which marks its activation, and phosphorylation of several of its downstream substrates. Importantly, all of these responses are detected in the nuclei of granule and Purkinje cells, suggesting that nuclear ATM functions in these cells similar to other cell types. These results support the notion that the cerebellar degeneration in A-T patients results from defective DNA damage response.
Visual Experience Regulates Metabotropic Glutamate Receptor-Mediated Plasticity of AMPA Receptor Synaptic Transmission by Homer1a Induction
Authors: Van Keuren-Jensen Kendall , Cline Hollis T.
Published: July 2006

Brief metabotropic glutamate receptor (mGluR) activation leads to plasticity of AMPA receptor (AMPAR) synaptic transmission. To test whether mGluR-mediated plasticity of AMPAR transmission is influenced by recent neuronal activity, we manipulated visual activity inXenopus laevistadpolesin vivo. We compared mGluR-mediated plasticity of AMPAR transmission in optic tectal cells of tadpoles with low levels of previous synaptic activity (overnight in the dark) to transmission in neurons from animals after 4 h of constant visual stimulation. mGluR-mediated plasticity of AMPA transmission was significantly decreased in neurons with recent activity. We tested the role of the activity-regulated mGluR scaffolding protein Homer1a in modulating mGluR-mediated changes in AMPAR transmission. We found that, by changing the ratios of Homer 1a to Homer 1bin vivo, by either induction of endogenous Homer1a by visual activity or ectopic expression of Homer1a or Homer1b, we could change the direction of mGluR-mediated plasticity. This is the first evidence that mGluR-mediated changes in AMPA transmission can be regulated by Homer proteins in response to physiologically relevant stimuli.
The Maize Ab10 Meiotic Drive System Maps to Supernumerary Sequences in a Large Complex Haplotype
Authors: Mroczek Rebecca J , Melo Juliana R , Luce Amy C , Hiatt Evelyn N , Dawe R Kelly
Published: July 2006

The meiotic drive system on maize abnormal chromosome 10 (Ab10) is contained within a terminal domain of chromatin that extends the long arm of Ab10 to ∼1.3 times the size of normal chromosome 10L. Ab10 type I (Ab10-I) does not recombine with normal chromosome 10 (N10) over an ∼32-cM terminal region of the long arm. Comparative RFLP mapping demonstrates that multiple independent rearrangements are responsible for the current organization of Ab10-I, including a set of nested inversions and at least one long supernumerary segment at the end of the chromosome. Four major meiotic drive functions, i.e., the recombination effect, smd3, 180-bp neocentromere activity, and the distal tip function, all map to the distal supernumerary segment. TR-1-mediated neocentromere activity (the fifth known drive function) is nonessential in the type II variant of Ab10 and maps to a central region that may include a second supernumerary insertion. Both neocentromere activity and the recombination effect behave as dominant gain-of-function mutations, consistent with the view that meiotic drive involves new or alien gene products. These and other data suggest that the Ab10 meiotic drive system was initially acquired from a related species and that a complex haplotype evolved around it.
The Tribolium castaneum Ortholog of Sex combs reduced Controls Dorsal Ridge Development
Authors: Shippy Teresa D , Rogers Carmelle D , Beeman Richard W , Brown Susan J , Denell Robin E
Published: July 2006

In insects, the boundary between the embryonic head and thorax is formed by the dorsal ridge, a fused structure composed of portions of the maxillary and labial segments. However, the mechanisms that promote development of this unusual structure remain a mystery. In Drosophila, mutations in the Hox genes Sex combs reduced and Deformed have been reported to cause abnormal dorsal ridge formation, but the significance of these abnormalities is not clear. We have identified three mutant allele classes of Cephalothorax, the Tribolium castaneum (red flour beetle) ortholog of Sex combs reduced, each of which has a different effect on dorsal ridge development. By using Engrailed expression to monitor dorsal ridge development in these mutants, we demonstrate that Cephalothorax promotes the fusion and subsequent dorsolateral extension of the maxillary and labial Engrailed stripes (posterior compartments) during dorsal ridge formation. Molecular and genetic analysis of these alleles indicates that the N terminus of Cephalothorax is important for the fusion step, but is dispensable for Engrailed stripe extension. Thus, we find that specific regions of Cephalothorax are required for discrete steps in dorsal ridge formation.
TheperiodGene Thr-Gly Polymorphism in Australian and AfricanDrosophila melanogasterPopulations: Implications for Selection
Authors: Sawyer Lesley A , Sandrelli Federica , Pasetto Carlo , Peixoto Alexandre A , Rosato Ezio , Costa Rodolfo , Kyriacou Charalambos P
Published: July 2006

The period gene is a key regulator of biological rhythmicity in Drosophila melanogaster. The central part of the gene encodes a dipeptide Thr-Gly repeat that has been implicated in the evolution of both circadian and ultradian rhythms. We have previously observed that length variation in the repeat follows a latitudinal cline in Europe and North Africa, so we have sought to extend this observation to the southern hemisphere. We observe a parallel cline in Australia for one of the two major length variants and find higher levels of some Thr-Gly length variants, particularly at the tropical latitudes, that are extremely rare in Europe. In addition we examined >40 haplotypes from sub-Saharan Africa and find a very different and far more variable profile of Thr-Gly sequences. Statistical analysis of the periodicity and codon content of the repeat from all three continents reveals a possible mechanism that may explain how the repeat initially arose in the ancestors of the D. melanogaster subgroup of species. Our results further reinforce the view that thermal selection may have contributed to shaping the continental patterns of Thr-Gly variability.
Regulation of DNA Replication Machinery by Mrc1 in Fission Yeast
Authors: Nitani Naoki , Nakamura Ken-ichi , Nakagawa Chie , Masukata Hisao , Nakagawa Takuro
Published: July 2006

Faithful replication of chromosomes is crucial to genome integrity. In yeast, the ORC binds replication origins throughout the cell cycle. However, Cdc45 binds these before S-phase, and, during replication, it moves along the DNA with MCM helicase. When replication progression is inhibited, checkpoint regulation is believed to stabilize the replication fork; the detailed mechanism, however, remains unclear. To examine the relationship between replication initiation and elongation defects and the response to replication elongation block, we used fission yeast mutants of Orc1 and Cdc45—orp1-4 and sna41-928, respectively—at their respective semipermissive temperatures with regard to BrdU incorporation. Both orp1 and sna41 cells exhibited HU hypersensitivity in the absence of Chk1, a DNA damage checkpoint kinase, and were defective in full activation of Cds1, a replication checkpoint kinase, indicating that normal replication is required for Cds1 activation. Mrc1 is required to activate Cds1 and prevent the replication machinery from uncoupling from DNA synthesis. We observed that, while either the orp1 or the sna41 mutation partially suppressed HU sensitivity of cds1 cells, sna41 specifically suppressed that of mrc1 cells. Interestingly, sna41 alleviated the defect in recovery from HU arrest without increasing Cds1 activity. In addition to sna41, specific mutations of MCM suppressed the HU sensitivity of mrc1 cells. Thus, during elongation, Mrc1 may negatively regulate Cdc45 and MCM helicase to render stalled forks capable of resuming replication.
Palladium‐Catalyzed Stereoselective Synthesis of (E)‐Stilbenes via Organozinc Reagents and Carbonyl Compounds
Authors: Wang Jin‐Xian , Wang Kehu , Zhao Lianbiao , Li Hongxia , Fu Ying , Hu Yulai
Published: July 2006

In the presence of a catalytic amount of PdCl2(PPh3)2 and a silylating agent, organozinc halides reacted with carbonyl compounds to give the corresponding (E)‐stilbenes in good to excellent yields under mild conditions. The reaction mechanism is briefly discussed.
The 3‐(3‐Pyridine)propionyl Anchor Group for Protease‐Catalyzed Resolutions: p‐Toluenesulfinamide and Sterically Hindered Secondary Alcohols
Authors: Savile Christopher K. , Kazlauskas Romas J.
Published: July 2006

Compared to an acetyl acyl group, the 3‐(3‐pyridine)propionyl group increases substrate binding to many proteases and substrate solubility in water, thereby increasing the rates of protease‐catalyzed reactions. For example, proteases reacted up to six hundred‐fold faster with the 3‐(3‐pyridine)propionyl ester of 1‐phenylethanol than with the corresponding acetate ester. In addition, the 3‐(3‐pyridine)propionyl group enables a simple, mild acid extraction to separate the remaining starting material and product. To demonstrate the synthetic usefulness of this strategy, we resolved multi‐gram quantities of (R)‐ and (S)‐p‐toluenesulfinamide with α‐chymotrypsin and gram quantities of (R)‐ and (S)‐2,2‐dimethylcyclopentanol with subtilisin Carlsberg. The 3‐(3‐pyridyl)propionyl group was better for these resolutions than the corresponding acetate or dihydrocinnamate because it decreased the reaction time due to increased reactivity, decreased the reaction volume due to increased substrate solubility and enabled purification without chromatography. Molecular modeling suggests the enantioselectivity of α‐chymotrypsin toward (R)‐p‐toluenesulfinamide is high (E=52) because of a favorable hydrophobic interaction between the p‐tolyl group of the fast‐reacting (R)‐enantiomer and leaving group pocket. The enantioselectivity of subtilisin Carlsberg toward (S)‐2,2‐dimethylcyclopentanol is high (E=43) because the large substituent (the 2,2‐dimethyl quaternary carbon) of the slow‐reacting (R)‐enantiomer cannot fit in the S1′ leaving group pocket.
Asymmetric Hydrogenation of α,β‐Unsaturated Carboxylic Acids Catalyzed by Ruthenium(II) Complexes of Spirobifluorene Diphosphine (SFDP) Ligands
Authors: Cheng Xu , Xie Jian‐Hua , Li Sheng , Zhou Qi‐Lin
Published: July 2006

The ruthenium diacetate complexes ligated by chiral spirobifluorene diphosphines (SFDP) were very effective catalysts for the asymmetric hydrogenation of tiglic acid derivatives and α‐methylcinnamic acid derivatives with high activities and excellent enantioselectivities (up to 98 % ee). The α‐aryloxybutenoic acids can also be hydrogenated by these catalysts to provide the corresponding saturated α‐aryloxybutanoic acids in high yields (89–93 %) and enantioselectivities (up to 95 % ee). In this reaction, the SFDP ligand with para‐methyl groups on the P‐phenyl rings gave the best results.
Catalytic Enantioselective Conjugate Addition of Nitromethane to α′‐Hydroxy Enones as Surrogates of α,β‐Unsaturated Carboxylic Acids and Aldehydes
Authors: Palomo Claudio , Pazos Raquel , Oiarbide Mikel , García Jesús M.
Published: July 2006

No base is required for the Mg(II)‐catalyzed conjugate addition of nitromethane to α′‐hydroxy enones in the presence of molecular sieves. Good enantioselectivities are attained using 3 or 4 Å MS and about 10 mol % of Mg(OTf)2‐chiral bisoxazoline complexes. Elaboration of the adducts through oxidative cleavage of the ketol moiety provides an entry to enantioenriched γ‐nitro carboxylic acids, while a sequential carbonyl reduction‐diol oxidation yields the corresponding aldehydes.
Activation of Nucleophilic Fluorination by Salts in Ionic Liquids and in Sulfolane
Authors: Anguille Stéphane , Garayt Maxime , Schanen Vincent , Grée René
Published: July 2006

The nucleophilic substitution of PhCCl3 by KF in imidazolium‐type RTILs is faster than in classical organic solvents but it is strongly dependent upon the nature of the counteranion. The addition of bromide salts in substoichoimetric amounts to the [bmim][PF6] solvent strongly accelerates this reaction. Furthermore, it has been discovered that addition of KPF6 to the reaction mixtures strongly activates the nucleophilic fluorination by KF, not only in the [bmim][NTf2] or [bmim][PF6] ionic liquids but also for the reactions performed in sulfolane.
Inhibition of eukaryotic translation initiation factor 5A (eIF5A) hypusination impairs melanoma growth
Authors: Jasiulionis Miriam G. , Luchessi Augusto D. , Moreira Andreia G. , Souza Pedro P. C. , Suenaga Ana P. M. , Correa Mariangela , Costa Carlos A. S. , Curi Rui , Costa‐Neto Claudio M.
Published: July 2006

The eukaryotic translation initiation factor 5A (eIF5A) undergoes a specific post‐translational modification called hypusination. This modification is required for the functionality of this protein. The compound N1‐guanyl‐1,7‐diaminoheptane (GC7) is a potent and selective inhibitor of deoxyhypusine synthase, which catalyses the first step of eIF5A hypusination process. In the present study, the effects of GC7 on cell death were investigated using two cell lines: melan‐a murine melanocytes and Tm5 murine melanoma. In vitro treatment with GC7 increased by 3‐fold the number of cells presenting DNA fragmentation in Tm5 cells. Exposure to GC7 also decreased viability to both cell lines. This study also describes, for the first time, the in vivo antitumour effect of GC7, as indicated by impaired melanoma growth in C57BL/6 mice. Copyright © 2006 John Wiley & Sons, Ltd.
Cardioprotection from ischemia‐reperfusion injury due to Ras‐GTPase inhibition is attenuated by glibenclamide in the globally ischemic heart
Authors: Al‐Rashdan Ibrahim , Canatan Halit , Al‐Maghrebi May , Yousif Mariam H. M. , Khan Shah A. , Benter Ibrahim F.
Published: July 2006

The present study was designed to see if acute local inhibition of Ras‐GTPase before or after ischemia (during perfusion) would produce protection against ischemia and reperfusion (I/R)‐induced cardiac dysfunction. The effect of glibenclamide, an inhibitor of cardiac mitochondrial ATP‐sensitive potassium (mitoKATP) channels, on Ras‐GTPase‐mediated cardioprotection was also studied. A 40 min episode of global ischemia followed by a 30 min reperfusion in perfused rat hearts produced significantly impaired cardiac function, measured as left ventricular developed pressure (Pmax) and left ventricular end‐diastolic pressure (LVEDP). Perfusion with Ras‐GTPase inhibitor FPT III before I/R [FPT(pre)], significantly enhanced cardiac recovery in terms of left ventricular contractility.Pmaxwas significantly higher at the end of 30 min reperfusion in FPT(pre)‐treated hearts compared to pre‐conditioned hearts. However, the degree of improvement in left ventricular contractility was significantly less when FPT III was given only after ischemia during reperfusion [FPT(post)]. Combination treatment with FPT III and glibenclamide before I/R resulted in significant reduction of FPT III‐mediated cardioprotection. These data suggest that activation of Ras‐GTPase signaling pathways during ischemia are critical in the development of left ventricular dysfunction and that opening of mitoKATPchannels, at least in part, contributes to cardioprotection produced by Ras‐GTPase inhibition. Copyright © 2006 John Wiley & Sons, Ltd.
Conformationally Restricted Aza‐BODIPY: Highly Fluorescent, Stable Near‐Infrared Absorbing Dyes
Authors: Zhao Weili , Carreira Erick M.
Published: July 2006

Novel NIR fluorescent, conformational restricted aza‐dipyrromethene boron difluoride (aza‐BODIPY) dyes were prepared by an efficient process. Such conformational restricted aza‐BODIPY dyes possess intense absorption, strong fluorescence, high chemical and photostability. Additionally, the sharp fluorescence of non‐amine containing aza‐BODIPY dyes is insensitive to solvent polarity.
Expression of vesicular glutamate transporter 1 immunoreactivity in peripheral and central endings of trigeminal mesencephalic nucleus neurons in the rat
Authors: Pang You Wang , Li Jin‐Lian , Nakamura Kouich , Wu Shengxi , Kaneko Takeshi , Mizuno Noboru
Published: July 2006

The major neuronal components of the trigeminal mesencephalic nucleus (Vmes) are primary afferent neurons that convey proprioceptive information from the cranioorofacial regions. In the present study, we examined expression of vesicular glutamate transporters (VGLUTs), VGLUT1 and VGLUT2, in the primary afferent neurons of the Vmes (Vmes neurons) in neonatal and adult rats. VGLUT1 immunoreactivity was detected in the cell bodies of Vmes neurons in neonatal rats younger than 11 days old, but not in older rats. However, in situ hybridization signals for VGLUT1 mRNA were detected in both neonatal and adult rats. No VGLUT2 immunoreactivity was detected in Vmes neurons of neonatal or adult rats. VGLUT1 immunoreactivity was also seen in the peripheral sensory endings on the equatorial regions of intrafusal fibers of muscle spindles in the masseter muscles in both neonatal and adult rats. In adult rats injected with cholera toxin B subunit (CTb) into the masseter nerve, central axon terminals of Vmes neurons were identified on masseter motoneurons within the trigeminal motor nucleus (Vm) by transganglionically and retrogradely transported CTb. VGLUT1‐immunopositive axon terminals in close apposition to CTb‐labeled Vm motoneurons were also detected by dual‐immunofluorescence histochemistry for VGLUT1/CTb. Electron microscopy after dual immunolabeling for VGLUT1/CTb by the VGLUT1/immunoperoxidase and CTb/immunogold‐silver methods further revealed synaptic contact of VGLUT1‐ and CTb‐immunopositive axon terminals upon CTb‐labeled neuronal profiles within the Vm. These data indicate that VGLUT1 is expressed in both the central axon terminals and the peripheral sensory endings of Vmes neurons, although no VGLUT1 immunoreactivity was detectable in the cell bodies of Vmes neurons in adult rats. J. Comp. Neurol. 498:129–141, 2006. © 2006 Wiley‐Liss, Inc.
Crystal Structure and Magnetic Behaviour of the New Gadolinium Carboxylates Gd2(ClF2CCOO)6(hypy)2, Gd2(F3CCOO)6(hypy)2, Gd2(F2HCCOO)6(hypy)2 and Gd2(Cl2HCCOO)6(H2O)2(hypy)2
Authors: John Daniela , Urland Werner
Published: July 2006

Four complexes with the formulae Gd2(ClF2CCOO)6(hypy)2 (1), Gd2(F3CCOO)6(hypy)2 (2), Gd2(F2HCCOO)6(hypy)2 (3) and Gd2(Cl2HCCOO)6(H2O)2(hypy)2 (4) have been synthesised and characterised by single‐crystal X‐ray diffraction methods at room temperature. The title compounds have been obtained by reaction of the corresponding gadolinium carboxylates with 4‐hydroxypyridine in a solution of ethanol and water. They crystallise in the triclinic space group P$\bar {1}$ (Z = 2) [1: a = 999.8(4) pm, b = 1061.8(5) pm, c = 1283.6(6) pm, α = 91.23(5)°, β = 111.29(5)° and γ = 105.27(5)°; 2: a = 972.4(4) pm, b = 1053.5(5) pm, c = 1252.4(6) pm, α = 94.23(5)°, β = 110.21(5)° and γ = 104.84(5)°; 3: a = 883.3(4) pm, b = 1051.3(4) pm, c = 1284.9(6) pm, α = 100.46(5)°, β = 109.87(5)° and γ = 97.43(5)°; 4: a = 913.7(4) pm, b = 1079.0(5) pm, c = 1137.5(5) pm, α = 93.41(5)°, β = 109.36(5)° and γ = 99.53(5)°]. The crystal structures consist of dinuclear Gd3+–Gd3+ units. The corresponding residuals (all data) for the refined structures are 4.82 % (1), 5.93 % (2), 5.68 % (3) and 4.04 % (4). The magnetic behaviour of the compounds was investigated over the temperature range 1.76–300 K. The magnetic data were interpreted by considering exchange interactions within the dimeric units [Jex = –0.019 cm–1 (1), Jex = –0.034 cm–1 (2), Jex = –0.064 cm–1 (3), Jex = –0.011 cm–1 (4)].(© Wiley‐VCH Verlag GmbH & Co. KGaA, 69451 Weinheim, Germany, 2006)
Simulated effect of a forest road on near‐surface hydrologic response: redux
Authors: Mirus Benjamin B. , Ebel Brian A. , Loague Keith , Wemple Beverley C.
Published: July 2006

In the work reported here the comprehensive physics‐based Integrated Hydrology Model (InHM) was employed to conduct both three‐ and two‐dimensional (3D and 2D) hydrologic‐response simulations for the small upland catchment known as C3 (located within the H. J. Andrews Experimental Forest in Oregon). Results from the 3D simulations for the steep unchannelled C3 (i) identify subsurface stormflow as the dominant hydrologic‐response mechanism and (ii) show the effect of the down‐gradient forest road on both the surface and subsurface flow systems. Comparison of the 3D results with the 2D results clearly illustrates the importance of convergent subsurface flow (e.g. greater pore‐water pressures in the hollow of the catchment for the 3D scenario). A simple infinite‐slope model, driven by subsurface pore‐water pressures generated from the 3D and 2D hydrologic‐response simulations, was employed to estimate slope stability along the long‐profile of the C3 hollow axis. As expected, the likelihood of slope failure is underestimated for the lower pore pressures from the 2D hydrologic‐response simulation compared, in a relative sense, to the higher pore pressures from the 3D hydrologic response simulation. The effort reported herein provides a firm quantitative foundation for generalizing the effects that forest roads can have on near‐surface hydrologic response and slope stability at the catchment scale. Copyright © 2006 John Wiley & Sons, Ltd.
Capture of extracellular zinc ions by astrocytes
Authors: Varea Emilio , Alonso‐Llosà Gregori , Molowny Asunción , Lopez‐Garcia Carlos , Ponsoda Xavier
Published: July 2006

Synaptic zinc ions released during synaptic transmission interact with pre‐ and postsynaptic neuroreceptors, thus modulating neurotransmission. It is likely that they have to be efficiently cleared from the extracellular milieu to assure subsequent synaptic events. Both neurons and glia are assumed to participate in this clearance by mechanisms that are not fully understood. In this study, electron microscopic zinc cytochemistry has shown zinc‐electrondense particles associated with hippocampal astrocytic membranes frequently found accumulated in stacked lamellae. In cultured astrocytes, the use of zinc fluorochromes and endocytic markers allowed the simultaneous imaging of the capture of extracellular zinc simultaneously to plasma membrane markers; this endocytic process was inhibited by high sucrose concentrations. Finally, electron microscopy of zinc‐loaded and fluorochrome photoconverted cells demonstrated some early events of extracellular zinc capture as well as its late accumulation in lysosome‐like organelles. © 2006 Wiley‐Liss, Inc.
Schwann cells and the pathogenesis of inherited motor and sensory neuropathies (Charcot‐Marie‐Tooth disease)
Authors: Berger Philipp , Niemann Axel , Suter Ueli
Published: July 2006

Over the last 15 years, a number of mutations in a variety of genes have been identified that lead to inherited motor and sensory neuropathies (HMSN), also called Charcot‐Marie‐Tooth disease (CMT). In this review we will focus on the molecular and cellular mechanisms that cause the Schwann cell pathologies observed in dysmyelinating and demyelinating forms of CMT. In most instances, the underlying gene defects alter primarily myelinating Schwann cells followed by secondary axonal degeneration. The first set of proteins affected by disease‐causing mutations includes the myelin components PMP22, P0/MPZ, Cx32/GJB1, and periaxin. A second group contains the regulators of myelin gene transcription EGR2/Krox20 and SOX10. A third group is composed of intracellular Schwann cells proteins that are likely to be involved in the synthesis, transport and degradation of myelin components. These include the myotubularin‐related lipid phosphatase MTMR2 and its regulatory binding partner MTMR13/SBF2, SIMPLE, and potentially also dynamin 2. Mutations affecting the mitochondrial fission factor GDAP1 may indicate an important contribution of mitochondria in myelination or myelin maintenance, whereas the functions of other identified genes, including NDRG1, KIAA1985, and the tyrosyl‐tRNA synthase YARS, are not yet clear. Mutations in GDAP1, YARS, and the pleckstrin homology domain of dynamin 2 lead to an intermediate form of CMT that is characterized by moderately reduced nerve conduction velocity consistent with minor myelin deficits. Whether these phenotypes originate in Schwann cells or in neurons, or whether both cell types are directly affected, remains a challenging question. However, based on the advances in systematic gene identification in CMT and the analyses of the function and dysfunction of the affected proteins, crucially interconnected pathways in Schwann cells in health and disease have started to emerge. These networks include the control of myelin formation and stability, membrane trafficking, intracellular protein sorting and quality control, and may extend to mitochondrial dynamics and basic protein biosynthesis. © 2006 Wiley‐Liss, Inc.
Social stigmatization in patients with cranial and cervical dystonia
Authors: Rinnerthaler Martina , Mueller Joerg , Weichbold Viktor , Wenning Gregor K. , Poewe Werner
Published: July 2006

Patients with cranial and cervical dystonia (CCD) suffer from visible involuntary facial, head, and neck movements. Therefore, the social appearance of patients with CCD may be seriously affected and self‐perceived stigma can be a major source of disability. The present study investigated enacted social stigmatization of patients with CCD. In a pilot study, a semantic differential scale for assessment of stigma was constructed and validated. The final scale contained eight items representing personality traits to be rated on a seven‐point scale (−3 negative extreme to 3 positive extreme). Short video sequences (15 seconds) of patients with various types of CCD and age‐ and sex‐matched healthy controls were presented to a sample of 80 biology students (mean age, 19.8 ± 2.3 years). Immediately after presentation of each video sequence, the students were asked to perform stigma ratings. Significant differences between CCD patients and controls were found on all eight items (P < 0.001 for each). CCD patients were rated as less accountable for their actions, less likeable, less trustworthy, less attractive, less self‐confident, more odd and different, more reserved, and more piteous than controls. CCD patients are subject to serious prejudice and enacted stigmatization. There is a need for informing the public about the nature and symptoms of this disorder and a need to support patients to cope with stigmatization. © 2006 Movement Disorder Society
Vascular endothelial growth factor in amyotrophic lateral sclerosis and other neurodegenerative diseases
Authors: Bogaert Elke , Damme Philip Van , Van Den Bosch Ludo , Robberecht Wim
Published: July 2006

The angiogenic activity of vascular endothelial growth factor (VEGF) is well known. Recently, it has become evident that VEGF is involved in central nervous system physiology and may play a role in the pathogenesis of neurological diseases. In particular, it may be involved in the mechanism of motor neuron degeneration in amyotrophic lateral sclerosis (ALS), and has been hypothesized to be implicated in the pathogenesis of peripheral neuropathies such as occur in the so‐called POEMS syndrome and diabetes. VEGF is also being studied as a possible treatment option in some of these disorders. In this review we critically analyze the data supporting the notion that VEGF is a factor involved in motor neuron degeneration and review the studies linking VEGF to other diseases of the peripheral and central nervous systems. Muscle Nerve, 2006
Precursor B‐cell acute lymphoblastic leukemia presenting with hemophagocytic lymphohistiocytosis
Authors: O'Brien Maureen M. , Lee‐Kim Youngna , George Tracy I. , McClain Kenneth L. , Twist Clare J. , Jeng Michael
Published: July 2006

Hemophagocytic lymphohistiocytosis (HLH) is a hyperinflammatory syndrome which can be an inherited congenital disorder or can develop secondary to malignancy, infection, or autoimmune disease. Secondary HLH due to malignancy occurs most commonly with T or NK‐cell lymphoid neoplasms. HLH with B‐cell malignancies is less common and HLH has rarely been described in association with precursor B‐cell acute lymphoblastic leukemia (B‐ALL). We report three cases of HLH associated with B‐ALL and review 17 cases of ALL‐associated HLH previously reported in the literature. Pediatr Blood Cancer 2008;50:381–383. © 2006 Wiley‐Liss, Inc.
Retinoblastoma and deletion of the long arm of chromosome 13: An underestimated diagnosis?
Authors: Brichard Bénédicte , Chantrain Christophe , Gala Jean‐Luc , Sibille Catherine , Vermylen Christiane , De Potter Patrick
Published: July 2006

We report an infant with normal neurological development and phenotype who developed bilateral retinoblastoma (RB). This patient, despite lack of dysmorphic features, demonstrated constitutional abnormality of the long arm of chromosome 13 on standard karyotype. We recommend systematic cytogenetic examinations complemented by fluorescent in situ hybridization as second‐line screening in all patients suspected for hereditary RB despite negative RB1 molecular screening and normal phenotype. Pediatr Blood Cancer 2008;50:694–696. © 2006 Wiley‐Liss, Inc.
A practical overview of protein disorder prediction methods
Authors: Ferron François , Longhi Sonia , Canard Bruno , Karlin David
Published: July 2006

In the past few years there has been a growing awareness that a large number of proteins contain long disordered (unstructured) regions that often play a functional role. However, these disordered regions are still poorly detected. Recognition of disordered regions in a protein is important for two main reasons: reducing bias in sequence similarity analysis by avoiding alignment of disordered regions against ordered ones, and helping to delineate boundaries of protein domains to guide structural and functional studies. As none of the available method for disorder prediction can be taken as fully reliable on its own, we present an overview of the methods currently employed highlighting their advantages and drawbacks. We show a few practical examples of how they can be combined to avoid pitfalls and to achieve more reliable predictions. Proteins 2006. © 2006 Wiley‐Liss, Inc.
Predictors for Complications after Loop Stoma Closure in Patients with Rectal Cancer
Authors: Pokorny Herwig , Herkner Harald , Jakesz Raimund , Herbst Friedrich
Published: July 2006

Purpose

This unmatched case control study was undertaken to evaluate factors contributing to surgery‐related complications of loop stoma closure in patients with rectal cancer.

Methods

Cases were consecutive patients with complications identified from a local registry. Complications were defined as surgery‐related and included 30 days overall mortality. Controls were all other patients with stoma closure from the same population of the registry without the endpoint.

Results

Of the 243 patients, 47 (19%) patients experienced a surgery‐related complication, including 5 patients who died within 30 days after surgery. Significant risk factors in the univariate analysis were supervised operation (odds ratio 0.50; 95% confidence interval 0.27–0.95; P = 0.04), stapled anastomosis (odds ratio 0.40; 95% confidence interval 0.17–0.91; P = 0.04) and using a soft silicone drain (odds ratio 2.03; 95% confidence interval 1.07–3.85; P = 0.04). Using a soft silicone drain (odds ratio 2.17; 95% confidence interval 1.10–4.26; P = 0.03) and stapled anastomosis (odds ratio 0.38; 95% confidence interval 0.15–0.98; P = 0.04) were the only significant predictors in the multivariate analysis.

Conclusions

The present study in a homogeneous group of patients with rectal cancer as elective indication for temporary loop stoma construction confirms the high complications rate and mortality rate associated with stoma closure. Intraperitoneal drains should be omitted after loop stoma closure.
The Transcript Levels of two Plant Mitochondrial Uncoupling Protein (pUCP)-Related Genes are not Affected by Hyperosmotic Stress in Durum Wheat Seedlings Showing an Increased Level of pUCP Activity
Authors: Trono Daniela , Soccio Mario , Mastrangelo Anna M. , De Simone Vanessa , Di Fonzo Natale , Pastore Donato
Published: July 2006

Etiolated early seedlings of durum wheat submitted to moderate and severe salt (NaCl) and osmotic (mannitol) stress showed no relevant increase of both transcript levels of two plant uncoupling protein (pUCP)-related genes and maximal pUCP activity in purified mitochondria (which estimates protein level); contrarily, pUCP functioning due to endogenous free fatty acids strongly increased. These results show that pUCP activation under hyperosmotic stress may be due to modulation of pUCP reaction rather than to an increased protein synthesis. Finally, a properly developed method, based on a single membrane potential measurement, to evaluate both pUCP maximal activity and functioning, is reported.
Holocene Environments and Soil Geomorphology in Midwestern United States
Authors: Ruhe Robert V.
Published: July 2006

In midwestern United States the most important widespread environmental event during the Holocene about 8000 y.a. was the establishment of an effective precipitation pattern that in part defines the Prairie Peninsula. The pattern occupies a region that is dominated by dry westerly air for 6–9 mo during normal years and for 9–12 mo during drought years. Regional soil geography correlates readily with zones of precipitation effectiveness with Brunizem (Udolls) conforming to the moist, subhumid zone, Chernozem (Boralls, Udolls) relating to the dry, subhumid zone, and Chestnut and Brown soils (Ustolls) fitting the semiarid zone. During the past few thousand years, a climatic reversal has caused encroachment of forest on prairie resulting in the formation of transitional or intergrade soils.

In local areas the Holocene is expressed on the land surface by the soil geomorphic unit which is the repetitive occurrence of a sequence of soils on the erosional surface of a hillslope and on the correlative depositional body at the foot and toe of the slope. This unit embraces time, lithology, landscape, and soils and provides a means for mapping the Holocene on the countryside.
Sea Level Events and Pleistocene Coral Ages in the Northern Bahamas
Authors: Neumann A. Conrad , Moore Willard S.
Published: July 2006

Emergent Pleistocene sea level indicators in the northern Bahamas include: a bioerosional notch at +5.3 to 5.9 m; sea caves, notches, and marine terraces at about +4.3 m; and lithified coral rubble and reef deposits between 0 and 3 m. Thorium 230 dates of the fossil corals, which were deposited as these features were being produced, span the age range from 100 to 145 thousand years BP with a majority falling between 115 and 130 thousand years BP. The notch at about +5.6 m is interpreted to be the product of a sea level stand 125 thousand years BP, while the features at +4.3 m are believed to be formed sometime later as sea level fell from the higher position. Part of the age span is inherent in the dating technique and possible sample alteration. Another cause of the spread may be mixing of corals of different ages into a single deposit.