bluuebunny/crossref_metadata_2025_split huggingface dataset:
Vitamin K2 induces phosphorylation of protein kinase A and expression of novel target genes in osteoblastic cells
Authors: Ichikawa T , Horie-Inoue K , Ikeda K , Blumberg B , Inoue S 
Published: October 2007

AbstractVitamin K is known as a critical nutrient required for bone homeostasis and blood coagulation, and it is clinically used as a therapeutic agent for osteoporosis in Japan. Besides its enzymatic action as a cofactor of vitamin K-dependent γ-glutamyl carboxylase (GGCX), we have previously shown that vitamin K2 is a transcriptional regulator of bone marker genes and extracellular matrix-related genes, by activating the steroid and xenobiotic receptor (SXR). To explore a novel action of vitamin K in osteoblastic cells, we identified genes up-regulated by a vitamin K2 isoform menaquinone-4 (MK-4) using oligonucleotide microarray analysis. Among these up-regulated genes by MK-4, growth differentiation factor 15 (GDF15) and stanniocalcin 2 (STC2) were identified as novel MK-4 target genes independent of GGCX and SXR pathways in human and mouse osteoblastic cells. The induction of GDF15 and STC2 is likely specific to MK-4, as it was not exerted by another vitamin K2 isoform MK-7, vitamin K1, or the MK-4 side chain structure geranylgeraniol. Investigation of the involved signaling pathways revealed that MK-4 enhanced the phosphorylation of protein kinase A (PKA), and the MK-4-dependent induction of both GDF15 and STC2 genes was reduced by the treatment with a PKA inhibitor H89 or siRNA against PKA. These results suggest that vitamin K2 modulates its target gene expression in osteoblastic cells through the PKA-dependent mechanism, which may be distinct from the previously known vitamin K signaling pathways.
POSTFIRE STAND STRUCTURE IN A SEMIARID SAVANNA: CROSS‐SCALE CHALLENGES ESTIMATING BIOMASS
Authors: Huang Cho-ying , Marsh Stuart E. , McClaran Mitchel P. , Archer Steven R. 
Published: October 2007

Algorithms relating remotely sensed woody cover to biomass are often the basis for large‐scale inventories of aboveground carbon stocks. However, these algorithms are commonly applied in a generic fashion without consideration of disturbances that might alter vegetation structure. We compared field and remote sensing estimates of woody biomass on savannas with contrasting disturbance (fire) histories and assessed potential errors in estimating woody biomass from cover without considering fire history. Field surveys quantified multilayer cover (MLC) of woody and succulent plants on sites experiencing wildfire in 1989 or 1994 and on nearby unburned (control) sites. Remote sensing estimates of the woody cover fraction (WCF) on burned and control sites were derived from contemporary (2005) dry‐season Landsat Thematic Mapper imagery (during a period when herbaceous cover was senescent) using a probabilistic spectral mixture analysis model. Satellite WCF estimates were compared to field MLC assessments and related to aboveground biomass using allometry.Field‐based MLC and remotely sensed WCFs both indicated that woody cover was comparable on control areas and areas burned 11–16 years ago. However, biomass was approximately twofold higher on control sites. Canopy cover was a strong predictor of woody biomass on burned and control areas, but fire history significantly altered the linear cover–biomass relationship on control plots to a curvilinear relationship on burned plots. Results suggest predictions of woody biomass from “generic” two‐dimensional (2‐D) cover algorithms may underestimate biomass in undisturbed stands and overestimate biomass in stands recovering from disturbance. Improving the accuracy of woody‐biomass estimates from field and/or remotely sensed cover may therefore require disturbance‐specific models or detection of vegetation height and transforming 2‐D vegetation cover to 3‐D vegetation volume.
TCF7L2 Is Not a Major Susceptibility Gene for Type 2 Diabetes in Pima Indians
Authors: Guo Tingwei , Hanson Robert L. , Traurig Michael , Li Muller Yunhua , Ma Lijun , Mack Janel , Kobes Sayuko , Knowler William C. , Bogardus Clifton , Baier Leslie J. 
Published: October 2007

OBJECTIVE— The transcription factor 7-like 2 (TCF7L2) gene was initially reported to be associated with type 2 diabetes in Icelandic, Danish, and U.S. populations. We investigated whether TCF7L2 also has a role in type 2 diabetes susceptibility in Pima Indians.
RESEARCH DESIGN AND METHODS— The six variants reported to be associated with type 2 diabetes in the Icelandic study were genotyped in a population-based sample of 3,501 Pima Indians (1,561 subjects had type 2 diabetes, and 1,940 did not have diabetes). In addition, the coding and promoter regions of TCF7L2 were sequenced in 24 Pima subjects. The one variant identified by sequencing, 35 additional database variants positioned in introns, and the six variants reported in the Icelandic study were genotyped in Pima families to determine the haplotype structure of TCF7L2 among Pima Indians. Fourteen representative variants were selected and genotyped in 3,501 Pima Indians.
RESULTS— The six variants initially reported to be associated with type 2 diabetes were less common in Pima Indians compared with samples of European origin, and none were associated with type 2 diabetes. One representative variant, rs1225404, was nominally associated with type 2 diabetes in a general model (additive P = 0.03, dominant P = 0.005) but not in a within-family analysis (additive P = 0.2, dominant P = 0.07). However, several variants were associated with BMI; in particular, rs12255372 was associated in both general and within-family analyses (both P = 0.0007). Modest associations were also found with traits predictive for type 2 diabetes.
CONCLUSIONS— Variation within TCF7L2 does not confer major risk for type 2 diabetes among the Pima Indian population.
Der Natur abgeschaut: β‐Faltblatt‐Oligopeptide und Analoga organisieren Blockcopolymere
Authors: König Hannah M. , Kilbinger Andreas F. M. 
Published: October 2007

AbstractDie Strukturen von Knäuel‐Knäuel‐Diblockcopolymeren in Lösung lassen sich durch die selektive Solvatation einzelner Blöcke erklären und sind mittlerweile gut untersucht. In den meisten Fällen verfügen diese relativ einfach aufgebauten Blockcopolymere über keinerlei spezifische attraktive Wechselwirkungen, die einen Aggregationsprozess unterstützen könnten. Demgegenüber sind in der Natur unzählige Beispiele definierter polymerer Architekturen zu finden, die hierarchisch über nichtkovalente Wechselwirkungen aufgebaut sind. Hoch definierte Strukturen, wie sie etwa die Proteine bilden, sind für synthetische Polymere bislang unbekannt. Ein relativ junges Forschungsgebiet der Polymerchemie widmet sich daher dem Ansatz, die in der Natur geltenden Prinzipien der Überstrukturbildung mit der Polymerchemie zu kombinieren, indem man Peptide mit β‐Faltblattstruktur an synthetische Polymere konjugiert. Von besonderem Interesse ist hierbei die supramolekulare Organisation der Polymere, die ausschließlich über die attraktiven Wechselwirkungen zwischen den Peptidsträngen hervorgerufen wird. Solche Peptid‐Polymer‐Hybridstrukturen sind eine interessante neue Materialklasse, die es zudem ermöglicht, wichtige Einblicke in natürlich vorkommende Selbstorganisationsprozesse zu erlangen.
Learning from Nature: β‐Sheet‐Mimicking Copolymers Get Organized
Authors: König Hannah M. , Kilbinger Andreas F. M. 
Published: October 2007

AbstractThe solution structures formed by coil–coil copolymers arise from the selective solvation of one of the two blocks and have been well described. In most cases in such relatively simple synthetic structures there are no specific attractive forces that can aid the aggregation process. Nature, however, provides plenty of inspiring polymeric architectures that are shaped and ordered hierarchically by noncovalent forces. The high level of structural definition displayed by proteins, for example, is unmatched by synthetic polymers. An emerging area of interest in polymer science tries to combine the best of both worlds, the natural and the synthetic, by conjugating synthetic polymers and β‐sheet‐forming peptides. Understanding the supramolecular organization of the block copolymers driven exclusively by the intermolecular attractive forces of the peptide sequence is of particular interest. Not only do these peptide–polymer hybrid structures present an interesting new class of materials, they can also provide important insights into self‐organization processes prevalent in nature.
Vinyl polymerization of norbornene by nickel(II) complexes bearing β‐diketiminate ligands
Authors: Li Yongfei , Gao Meili , Wu Qing 
Published: October 2007

AbstractNorbornene polymerizations were carried out using nickel(II) bromide complexes CH{C(R)NAr}2NiBr (1, R = CH3, Ar = 2, 6 − iPr2C6H3; 2, R = CH3, Ar = 2, 6‐Me2C6H3; 3, R = CF3, Ar = 2, 6 − iPr2C6H3; 4, R = CF3, Ar = 2, 6‐Me2C6H3) in the presence of methylaluminoxane. Compound 3 is the most active norbornene polymerization catalyst of all the nickel complexes tested. The activity of theses catalysts increases with increases in steric bulk of the substituents on the aryl rings. The electronic nature of the ligand backbone also affects the activity. The resulting polynorbornenes are vinyl type by IR and NMR analyses. Copyright © 2007 John Wiley & Sons, Ltd.
Rifalazil and Other Benzoxazinorifamycins in the Treatment of Chlamydia‐Based Persistent Infections
Authors: Rothstein David M. , van Duzer John , Sternlicht Andrew , Gilman Steven C. 
Published: October 2007

AbstractRifalazil is a benzoxazinorifamycin which inhibits bacterial DNA‐dependent RNA polymerase. The benzoxazine ring endows benzoxazinorifamycins with unique physical and chemical characteristics which favor the use of rifalazil and derivatives in treating diseases caused by the obligate intracellular pathogens of the genus chlamydia. Minimal inhibitory concentrations of benzoxazinorifamycins against chlamydia are in the pg/mL range. These compounds have potential as monotherapeutic agents to treat chlamydia‐associated disease because they retain activity against chlamydia strains resistant to currently approved rifamycins such as rifampin. A pivotal clinical trial with rifalazil has been initiated for the treatment of peripheral arterial disease. The rationale for this innovative use of rifalazil, including the association of C. pneumoniae in atherosclerotic plaque formation, as well as rifalazil's potency and efficacy against chlamydia in both preclinical and clinical studies, is discussed. Other benzoxazino derivatives may have utility as stand‐alone topical antibacterials or combination antibacterials to treat serious Gram‐positive infections. None of the benzoxaminorifamycins examined to date induce the cytochrome P450 3A4 enzyme. This is in contrast to currently approved rifamycins which are strong inducers of P450 enzymes, resulting in drug–drug interactions that limit the clinical utility of this drug class.
Linking Two Distinct Layered Networks of Nanosized {Ln18} and {Cu24} Wheels through Isonicotinate Ligands
Authors: Cheng Jian‐Wen , Zhang Jie , Zheng Shou‐Tian , Yang Guo‐Yu 
Published: October 2007

AbstractA new series of heterolanthanide(III)‐copper(I) wheel‐cluster complexes [Ln6(μ3‐O)2](IN)18[Cu8(μ4‐I)2(μ2‐I)3]⋅H3O (IN=isonicotinate; Ln=Y 1, Nd 2, Dy 3, Gd 4, Sm 5, Eu 6, Tb 7) were prepared by hydrothermal reaction at low pH. X‐ray crystallographic studies reveal that two unusual trinuclear [Ln3(μ3‐O)] and tetranuclear [Cu4(μ4‐I)] cores are successfully used as secondary building units to make two different nanosized wheels [Ln18(μ3‐O)6(CO2)48]6−, {Ln18}, and [Cu24(μ4‐I)6(μ2‐I)12]6+, {Cu24}, with 12‐rings and a diameter of 26.7 and 26.4 Å, respectively. The wheels are further assembled into two‐dimensional (2D) {Ln18} and {Cu24} networks, the linkages between two distinct layered networks of {Ln18} and {Cu24} wheels by IN pillars along the c axis giving a series of unprecedented three‐dimensional (3D) sandwich frameworks. To our knowledge, compounds 1–7 are the first examples containing two different layered networks of nanosized Ln and transition metal (TM) wheels in wheel‐cluster chemistry. The IR, UV/Vis, thermogravimetric analysis (TGA), luminescent, and magnetic properties of these complexes were also studied.
Chemical and morphological alterations of spines within the hippocampus and entorhinal cortex precede the onset of Alzheimer's disease pathology in double knock‐in mice
Authors: Aoki Chiye , Mahadomrongkul Veeravan , Fujisawa Sho , Habersat Rebecca , Shirao Tomoaki 
Published: October 2007

AbstractMice with knock‐in of two mutations that affect beta amyloid processing and levels (2xKI) exhibit impaired spatial memory by 9–12 months of age, together with synaptic plasticity dysfunction in the hippocampus. The goal of this study was to identify changes in the molecular and structural characteristics of synapses that precede and thus could exert constraints upon cellular mechanisms underlying synaptic plasticity. Drebrin A is one protein reported to modulate spine sizes and trafficking of proteins to and from excitatory synapses. Thus, we examined levels of drebrin A within postsynaptic spines in the hippocampus and entorhinal cortex. Our electron microscopic immunocytochemical analyses reveal that, by 6 months, the proportion of hippocampal spines containing drebrin A is reduced and this change is accompanied by an increase in the mean size of spines and decreased density of spines. In the entorhinal cortex of 2xKI brains, we detected no decrement in the proportion of spines labeled for drebrin A and no significant change in spine density at 6 months, but rather a highly significant reduction in the level of drebrin A immunoreactivity within each spine. These changes are unlike those observed for the somatosensory cortex of 2xKI mice, in which synapse density and drebrin A immunoreactivity levels remain unchanged at 6 months and older. These results indicate that brains of 2xKI mice, like those of humans, exhibit regional differences of vulnerability, with the hippocampus exhibiting the first signatures of structural changes that, in turn, may underlie the emergent inability to update spatial memory in later months. J. Comp. Neurol. 505:352–362, 2007. © 2007 Wiley‐Liss, Inc.
Distribution of corticotropin‐releasing hormone in the developing zebrafish brain
Authors: Chandrasekar Gayathri , Lauter Gilbert , Hauptmann Giselbert 
Published: October 2007

AbstractCorticotropin‐releasing hormone (CRH) plays a central role in the physiological regulation of the hypothalamus‐pituitary‐adrenal/interrenal axis mediating endocrine, behavioral, autonomic, and immune responses to stress. Despite the wealth of knowledge about the physiological roles of CRH, the genetic mechanisms by which CRH neurons arise during development are poorly understood. As a first step toward analyzing the molecular and genetic pathways involved in CRH lineage specification, we describe the developmental distribution of CRH neurons in the embryonic zebrafish, a model organism for functional genomics and developmental biology. We searched available zebrafish expressed sequence tag (EST) databases for CRH‐like sequences and identified one EST that contained the complete zebrafish CRH open reading frame (ORF). The CRH precursor sequence contained a signal peptide, the CRH peptide, and a cryptic peptide with a conserved sequence motif. RT‐PCR analysis showedcrhexpression in a wide range of adult tissues as well as during embryonic and larval stages. By whole‐mount in situ hybridization histochemistry, discretecrh‐expressing cell clusters were found in different parts of the embryonic zebrafish brain, including telencephalon, preoptic region, hypothalamus, posterior tuberculum, thalamus, epiphysis, midbrain tegmentum, and rostral hindbrain and in the neural retina. The localization ofcrhmRNA within the preoptic region is consistent with the central role of CRH in the teleost stress response through activation of the hypothalamic‐pituitary‐interrenal axis. The widespread distribution of CRH‐synthesizing cells outside the preoptic region suggests additional functions of CRH in the embryonic zebrafish brain. J. Comp. Neurol. 505:337–351, 2007. © 2007 Wiley‐Liss, Inc.
The potassium channel KCNQ5/Kv7.5 is localized in synaptic endings of auditory brainstem nuclei of the rat
Authors: Caminos Elena , Garcia‐Pino Elisabet , Martinez‐Galan Juan Ramon , Juiz José M. 
Published: October 2007

AbstractKCNQ, also called Kv7, is a family of voltage‐dependent potassium channels with important roles in excitability regulation. Of its five known subunits, KCNQ5/Kv7.5 is extensively expressed in the central nervous system and it contributes to the generation of M‐currents. The distribution of KCNQ5 was analyzed in auditory nuclei of the rat brainstem by high‐resolution immunocytochemistry. Double labeling with anti‐KCNQ5 antibodies and anti‐synaptophysin or anti‐syntaxin, which mark synaptic endings, or anti‐microtubule‐associated protein 2 (MAP2) antibodies, which mark dendrites, were used to analyze the subcellular distribution of KCNQ5 in neurons in the cochlear nucleus, superior olivary complex, nuclei of the lateral lemniscus, and inferior colliculus. An abundance of KCNQ5 labeling in punctate structures throughout auditory brainstem nuclei along with colocalization with such synaptic markers suggests that a preferred localization of KCNQ5 is in synaptic endings in these auditory nuclei. Punctate KCNQ5 immunoreactivity virtually disappeared from the cochlear nucleus after cochlea removal, which strongly supports localization of this channel in excitatory endings of the auditory nerve. Actually, neither glycinergic endings, labeled with an anti‐glycine transporter 2 (GlyT2) antibody, nor γ‐aminobutyric acid (GABA)ergic endings, labeled with an anti‐glutamic acid decarboxylase (GAD65) antibody, contained KCNQ5 immunoreactivity, suggesting that KCNQ5 is mostly in excitatory endings throughout the auditory brainstem. Overlap of KCNQ5 and MAP2 labeling indicates that KCNQ5 is also targeted to dendritic compartments. These findings predict pre‐ and postsynaptic roles for KCNQ5 in excitability regulation in auditory brainstem nuclei, at the level of glutamatergic excitatory endings and in dendrites. J. Comp. Neurol. 505:363–378, 2007. © 2007 Wiley‐Liss, Inc.
Effects of inflammation on the ultrastructural localization of spinal cord dorsal horn group I metabotropic glutamate receptors
Authors: Pitcher Mark H. , Ribeiro‐Da‐Silva Alfredo , Coderre Terence J. 
Published: October 2007

AbstractInflammatory pain is thought to induce functional plasticity of spinal dorsal horn neurons and may produce changes in glutamate receptor expression. Plasticity of group I metabotropic glutamate receptors (mGluR1 and mGluR5) is important in various neuronal systems, and these receptors are also known to modulate nociceptive neurotransmission in the spinal dorsal horn. The present study aimed at determining whether persistent inflammatory pain produces alterations in intracellular and plasma membrane‐associated mGluR1α and mGluR5 in spinal cord dorsal horn. Persistent inflammation was induced in male Long Evans rats by a unilateral intraplantar injection of 100 μL of complete Freund's adjuvant (CFA). Three days after the CFA injection thermal withdrawal latencies were obtained prior to processing of transverse spinal cord sections for preembedding immunogold labeling after incubation in primary antibody for mGluR1α or mGluR5. Using electron microscopy, we quantified immunogold‐labeled mGluR1α and mGluR5 profiles, located in lamina V and I–II, respectively, of both CFA‐treated rats and untreated control rats. Compared to untreated rats, CFA‐treated rats had a significant increase in the number of plasma membrane‐associated mGluR5 immunogold‐labeled particles in lamina I–II neurons of the spinal cord. Although no changes to mGluR1α expression were found in CFA‐treated rats, plasma membrane‐associated mGluR1α was significantly closer to the synapse. Therefore, in CFA‐treated rats there was a specific increase in the ratio of plasma membrane‐associated versus intracellular immunogold‐labeled particles for mGluR5, and lateral movement of mGluR1α toward the synapse, indicating that peripheral inflammation‐induced trafficking of group I mGluRs in spinal dorsal horn neurons may be an important factor in the development of plastic changes associated with inflammation‐induced chronic pain. J. Comp. Neurol. 505:412–423, 2007. © 2007 Wiley‐Liss, Inc.
Spatial and temporal activation of brain regions in hibernation: c‐fos expression during the hibernation bout in thirteen‐lined ground squirrel
Authors: Bratincsák András , McMullen David , Miyake Shinichi , Tóth Zsuzsanna E. , Hallenbeck John M. , Palkovits Miklós 
Published: October 2007

AbstractHibernation results in dramatic changes in body temperature and metabolism; however, the central nervous system remains active during deep torpor. By cloning c‐fos cDNA from the 13‐lined ground squirrel (Spermophilus tridecemlineatus) and using squirrel c‐fos mRNA probe for in situ hybridization histochemistry, we systematically analyzed and identified specific brain regions that were activated during six different phases of the hibernation bout. During entrance into torpor, we detected activation of the ventrolateral subdivision of the medial preoptic area (‘thermoregulatory center’), and the reticular thalamic nucleus, which is known to inhibit the somatomotor cortex. During torpor, c‐fos expression in the cortex was suppressed while the reticular thalamic nucleus remained uniformly active. Throughout torpor the suprachiasmatic nucleus (‘biological clock’) showed increasing activity, likely participating in phase‐change regulation of the hibernation bout. Interestingly, during torpor very strong c‐fos activation was seen in the epithelial cells of the choroid plexus and in tanycytes at the third ventricle, both peaking near the beginning of arousal. In arousal, activity of the suprachiasmatic and reticular thalamic nuclei and choroid epithelial cells diminished, while ependymal cells in the lateral and fourth ventricles showed stronger activity. Increasing body temperature during arousal was driven by the activation of neurons in the medial part of the preoptic area. In interbout awake animals, we demonstrated the activation of hypothalamic neurons located in the arcuate nucleus and the dorsolateral hypothalamus, areas involved in food intake. Our observations indicate that the hibernation bout is closely regulated and orchestrated by specific regions of the central nervous system. J. Comp. Neurol. 505:443–458, 2007. © 2007 Wiley‐Liss, Inc.
Atypical embryonic synapses fail to regenerate in adulthood
Authors: Kloos Anne D. , Muller Kenneth J. , Modney Barbara K. 
Published: October 2007

AbstractFunctional recovery following central nervous system (CNS) injury in adult animals may depend on the reestablishment of the precise pattern of connections made during development. When the nervous system is injured during embryonic development, functional recovery may involve the formation of atypical connections. Can such atypical synapses regenerate in adults, particularly in a nervous system known for its capacity for repair? When the S interneuron in one segmental ganglion of the leech Hirudo is killed during development, two neighboring S cells extend their axons into the ganglion and restore function by making electrical synapses with the usual synaptic targets of the killed S cell. Although adult S‐cell axons reliably regenerated their usual synaptic connections, the novel synapses induced following embryonic injury failed to regenerate in adults. In these preparations severed S‐cell axons did not reach the denervated ganglion but grew close to it, independent of the distance required to grow. Thus, the developmental changes that permit aberrant but functional connections in embryos do not lead to a similar change in the capacity for axon growth and subsequent synapse regeneration in adults. J. Comp. Neurol. 505:404–411, 2007. © 2007 Wiley‐Liss, Inc.