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  • Proceedings of the National Academy of Sciences  (29)
  • 2000-2004  (29)
  • 11
    Online Resource
    Online Resource
    Proceedings of the National Academy of Sciences ; 2004
    In:  Proceedings of the National Academy of Sciences Vol. 101, No. 14 ( 2004-04-06), p. 5053-5057
    In: Proceedings of the National Academy of Sciences, Proceedings of the National Academy of Sciences, Vol. 101, No. 14 ( 2004-04-06), p. 5053-5057
    Abstract: Human cortical activity has been intensively examined at frequencies ranging from 0.5 Hz to several hundred Hz. Recent studies have, however, reported also infraslow fluctuations in neuronal population activity, magnitude of electroencephalographic oscillations, discrete sleep events, as well as in the occurrence of interictal events. Here we use direct current electroencephalography to demonstrate large-scale infraslow oscillations in the human cortex at frequencies ranging from 0.02 to 0.2 Hz. These oscillations, which are not detectable in conventional electroencephalography because of its limited recording bandwidth (typical lower limit 0.5 Hz), were observed in widespread cortical regions. Notably, the infraslow oscillations were strongly synchronized with faster activities, as well as with the interictal epileptic events and K complexes. Our findings suggest that the infraslow oscillations represent a slow, cyclic modulation of cortical gross excitability, providing also a putative mechanism for the as yet enigmatic aggravation of epileptic activity during sleep.
    Type of Medium: Online Resource
    ISSN: 0027-8424 , 1091-6490
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    Language: English
    Publisher: Proceedings of the National Academy of Sciences
    Publication Date: 2004
    detail.hit.zdb_id: 209104-5
    detail.hit.zdb_id: 1461794-8
    SSG: 11
    SSG: 12
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  • 12
    Online Resource
    Online Resource
    Proceedings of the National Academy of Sciences ; 2001
    In:  Proceedings of the National Academy of Sciences Vol. 98, No. 26 ( 2001-12-18), p. 14865-14870
    In: Proceedings of the National Academy of Sciences, Proceedings of the National Academy of Sciences, Vol. 98, No. 26 ( 2001-12-18), p. 14865-14870
    Abstract: Abl family nonreceptor tyrosine kinases regulate cellular morphogenesis and motility through functional interactions with the actin cytoskeleton. Although Abl family kinases are known to contain filamentous (F)-actin-binding domains at their C termini, it is unclear how Abl family kinases regulate the structure and/or function of the actin cytoskeleton. We show here that the Abl-related kinase Arg binds with positive cooperativity to F-actin in vitro with binding saturating at a ratio of one Arg/two actin molecules. Measurements of the F-actin-binding properties of Arg deletion mutants led to the identification of a second, previously uncharacterized internal F-actin-binding domain in Arg. Purified Arg can bundle F-actin in vitro , and this bundling activity requires both F-actin-binding domains. An Arg-yellow fluorescent protein fusion protein can induce the formation of actin-rich structures at the lamellipodia of Swiss 3T3 fibroblasts. Both of Arg's F-actin-binding domains are necessary and sufficient for the formation of these actin-rich structures. Together, our data suggest that Arg can use its F-actin-bundling activity to directly regulate actin cytoskeletal structure in vivo .
    Type of Medium: Online Resource
    ISSN: 0027-8424 , 1091-6490
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    Language: English
    Publisher: Proceedings of the National Academy of Sciences
    Publication Date: 2001
    detail.hit.zdb_id: 209104-5
    detail.hit.zdb_id: 1461794-8
    SSG: 11
    SSG: 12
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  • 13
    In: Proceedings of the National Academy of Sciences, Proceedings of the National Academy of Sciences, Vol. 101, No. 18 ( 2004-05-04), p. 6929-6933
    Abstract: Mate attraction in Aplysia involves a long-distance water-borne signal (the protein pheromone attractin), which is released during egg laying. Aplysia californica attractin attracts species that produce closely related attractins, such as Aplysia brasiliana , whose geographic distribution does not overlap that of A. californica . This finding suggests that other mollusks release attractin-related pheromones to form and maintain breeding aggregations. We describe four additional members of the attractin family: A. brasiliana , Aplysia fasciata , Aplysia depilans (which aggregates with A. fasciata aggregations), and Aplysia vaccaria (which aggregates with A. californica aggregations). On the basis of their sequence similarity with A. californica attractin, the attractin proteins fall into two groups: A. californica , A. brasiliana , and A. fasciata (91–95% identity), and A. depilans and A. vaccaria (41–43% identity). The sequence similarity within the attractin family, the conserved six cysteines, and the compact fold of the NMR solution structure of A. californica attractin suggest a common fold for this pheromone family containing two antiparallel helices. The second helix contains the IEECKTS sequence conserved in Aplysia attractins. Mutating surface-exposed charged residues within this heptapeptide sequence abolishes attractin activity, suggesting that the second helix is an essential part of the receptor-binding interface.
    Type of Medium: Online Resource
    ISSN: 0027-8424 , 1091-6490
    RVK:
    RVK:
    Language: English
    Publisher: Proceedings of the National Academy of Sciences
    Publication Date: 2004
    detail.hit.zdb_id: 209104-5
    detail.hit.zdb_id: 1461794-8
    SSG: 11
    SSG: 12
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  • 14
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    Proceedings of the National Academy of Sciences ; 2003
    In:  Proceedings of the National Academy of Sciences Vol. 100, No. 25 ( 2003-12-09), p. 14719-14724
    In: Proceedings of the National Academy of Sciences, Proceedings of the National Academy of Sciences, Vol. 100, No. 25 ( 2003-12-09), p. 14719-14724
    Abstract: We used stopped-flow calorimetry to measure the overall enthalpy change associated with template-directed nucleotide insertion and DNA extension. Specifically, we used families of hairpin self-priming templates in conjunction with an exonuclease-free DNA polymerase to study primer extension by one or more dA or dT residues. Our results reveal exothermic heats between –9.8 and –16.0 kcal/bp for template-directed enzymatic polymerization. These extension enthalpies depend on the identity of the inserting base, the primer terminus, and/or the preceding base. Despite the complexity of the overall process, the sign, magnitude, and sequence dependence of these insertion and extension enthalpies are consistent with nearest-neighbor data derived from DNA melting studies. We recognize that the overall process studied here involves contributions from a multitude of events, including dNTP to dNMP hydrolysis, phosphodiester bond formation, and enzyme conformational changes. It is therefore noteworthy that the overall enthalpic driving force per base pair is of a magnitude similar to that expected for addition of one base pair or base stack per insertion event, rather than that associated with the rupture and/or formation of covalent bonds, as occurs during this catalytic process. Our data suggest a constant sequence-independent background of compensating enthalpic contributions to the overall process of DNA synthesis, with discrimination expressed by differences in noncovalent interactions at the template–primer level. Such enthalpic discrimination underscores a model in which complex biological events are regulated by relatively modest energy balances involving weak interactions, thereby allowing subtle mechanisms of regulation.
    Type of Medium: Online Resource
    ISSN: 0027-8424 , 1091-6490
    RVK:
    RVK:
    Language: English
    Publisher: Proceedings of the National Academy of Sciences
    Publication Date: 2003
    detail.hit.zdb_id: 209104-5
    detail.hit.zdb_id: 1461794-8
    SSG: 11
    SSG: 12
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  • 15
    Online Resource
    Online Resource
    Proceedings of the National Academy of Sciences ; 2001
    In:  Proceedings of the National Academy of Sciences Vol. 98, No. 4 ( 2001-02-13), p. 1982-1987
    In: Proceedings of the National Academy of Sciences, Proceedings of the National Academy of Sciences, Vol. 98, No. 4 ( 2001-02-13), p. 1982-1987
    Abstract: Abnormal dopaminergic transmission is implicated in schizophrenia, attention deficit hyperactivity disorder, and drug addiction. In an attempt to model aspects of these disorders, we have generated hyperdopaminergic mutant mice by reducing expression of the dopamine transporter (DAT) to 10% of wild-type levels (DAT knockdown). Fast-scan cyclic voltammetry and in vivo microdialysis revealed that released dopamine was cleared at a slow rate in knockdown mice, which resulted in a higher extracellular dopamine concentration. Unlike the DAT knockout mice, the DAT knockdown mice do not display a growth retardation phenotype. They have normal home cage activity but display hyperactivity and impaired response habituation in novel environments. In addition, we show that both the indirect dopamine receptor agonist amphetamine and the direct agonists apomorphine and quinpirole inhibit locomotor activity in the DAT knockdown mice, leading to the hypothesis that a shift in the balance between dopamine auto and heteroreceptor function may contribute to the therapeutic effect of psychostimulants in attention deficit hyperactivity disorder.
    Type of Medium: Online Resource
    ISSN: 0027-8424 , 1091-6490
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    Language: English
    Publisher: Proceedings of the National Academy of Sciences
    Publication Date: 2001
    detail.hit.zdb_id: 209104-5
    detail.hit.zdb_id: 1461794-8
    SSG: 11
    SSG: 12
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  • 16
    In: Proceedings of the National Academy of Sciences, Proceedings of the National Academy of Sciences, Vol. 99, No. 9 ( 2002-04-30), p. 6328-6333
    Abstract: Rhodopsin is the G protein-coupled receptor that is activated by light and initiates the transduction cascade leading to night (rod) vision. Naturally occurring pathogenic rhodopsin ( RHO ) mutations have been previously identified only in humans and are a common cause of dominantly inherited blindness from retinal degeneration. We identified English Mastiff dogs with a naturally occurring dominant retinal degeneration and determined the cause to be a point mutation in the RHO gene (Thr4Arg). Dogs with this mutant allele manifest a retinal phenotype that closely mimics that in humans with RHO mutations. The phenotypic features shared by dog and man include a dramatically slowed time course of recovery of rod photoreceptor function after light exposure and a distinctive topographic pattern to the retinal degeneration. The canine disease offers opportunities to explore the basis of prolonged photoreceptor recovery after light in RHO mutations and determine whether there are links between the dysfunction and apoptotic retinal cell death. The RHO mutant dog also becomes the large animal needed for preclinical trials of therapies for a major subset of human retinopathies.
    Type of Medium: Online Resource
    ISSN: 0027-8424 , 1091-6490
    RVK:
    RVK:
    Language: English
    Publisher: Proceedings of the National Academy of Sciences
    Publication Date: 2002
    detail.hit.zdb_id: 209104-5
    detail.hit.zdb_id: 1461794-8
    SSG: 11
    SSG: 12
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  • 17
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    Online Resource
    Proceedings of the National Academy of Sciences ; 2000
    In:  Proceedings of the National Academy of Sciences Vol. 97, No. 8 ( 2000-04-11), p. 3936-3941
    In: Proceedings of the National Academy of Sciences, Proceedings of the National Academy of Sciences, Vol. 97, No. 8 ( 2000-04-11), p. 3936-3941
    Abstract: We have found that the bacterial transposon Tn 7 can recognize and preferentially insert adjacent to triple-helical nucleic acid structures. Both synthetic intermolecular triplexes, formed through the pairing of a short triplex-forming oligonucleotide on a plasmid DNA, and naturally occurring mirror repeat sequences known to form intramolecular triplexes or H-form DNA are preferential targets for Tn 7 insertion in vitro . This target site selectivity depends upon the recognition of the triplex region by a Tn 7 -encoded ATP-using protein, TnsC, which controls Tn 7 target site selection: the interaction of TnsC with the triplex region results in recruitment and activation of the Tn 7 transposase. Recognition of a nucleic acid structural motif provides both new information into the factors that influence Tn 7 's target site selection and broadens its targeting capabilities.
    Type of Medium: Online Resource
    ISSN: 0027-8424 , 1091-6490
    RVK:
    RVK:
    Language: English
    Publisher: Proceedings of the National Academy of Sciences
    Publication Date: 2000
    detail.hit.zdb_id: 209104-5
    detail.hit.zdb_id: 1461794-8
    SSG: 11
    SSG: 12
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  • 18
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    Proceedings of the National Academy of Sciences ; 2000
    In:  Proceedings of the National Academy of Sciences Vol. 97, No. 9 ( 2000-04-25), p. 4475-4480
    In: Proceedings of the National Academy of Sciences, Proceedings of the National Academy of Sciences, Vol. 97, No. 9 ( 2000-04-25), p. 4475-4480
    Abstract: Pax genes encode a family of transcription factors, many of which play key roles in animal embryonic development but whose evolutionary relationships and ancestral functions are unclear. To address these issues, we are characterizing the Pax gene complement of the coral Acropora millepora , an anthozoan cnidarian. As the simplest animals at the tissue level of organization, cnidarians occupy a key position in animal evolution, and the Anthozoa are the basal class within this diverse phylum. We have identified four Pax genes in Acropora : two ( Pax-Aam and Pax-Bam ) are orthologs of genes identified in other cnidarians; the others ( Pax-Cam and Pax-Dam ) are unique to Acropora. Pax-Aam may be orthologous with Drosophila Pox neuro , and Pax-Bam clearly belongs to the Pax-2 / 5 / 8 class. The Pax-Bam Paired domain binds specifically and preferentially to Pax-2/5/8 binding sites. The recently identified Acropora gene Pax-Dam belongs to the Pax-3 / 7 class. Clearly, substantial diversification of the Pax family occurred before the Cnidaria/higher Metazoa split. The fourth Acropora Pax gene, Pax-Cam , may correspond to the ancestral vertebrate Pax gene and most closely resembles Pax-6 . The expression pattern of Pax-Cam , in putative neurons, is consistent with an ancestral role of the Pax family in neural differentiation and patterning. We have determined the genomic structure of each Acropora Pax gene and show that some splice sites are shared both between the coral genes and between these and Pax genes in triploblastic metazoans. Together, these data support the monophyly of the Pax family and indicate ancient origins of several introns.
    Type of Medium: Online Resource
    ISSN: 0027-8424 , 1091-6490
    RVK:
    RVK:
    Language: English
    Publisher: Proceedings of the National Academy of Sciences
    Publication Date: 2000
    detail.hit.zdb_id: 209104-5
    detail.hit.zdb_id: 1461794-8
    SSG: 11
    SSG: 12
    Location Call Number Limitation Availability
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  • 19
    Online Resource
    Online Resource
    Proceedings of the National Academy of Sciences ; 2002
    In:  Proceedings of the National Academy of Sciences Vol. 99, No. 6 ( 2002-03-19), p. 3860-3865
    In: Proceedings of the National Academy of Sciences, Proceedings of the National Academy of Sciences, Vol. 99, No. 6 ( 2002-03-19), p. 3860-3865
    Abstract: Immunity to Plasmodium falciparum in African children has been correlated with antibodies to the P. falciparum erythrocyte membrane protein 1 (PfEMP1) variant gene family expressed on the surface of infected red cells. We immunized Aotus monkeys with a subregion of the Malayan Camp variant antigen (MCvar1) that mediates adhesion to the host receptor CD36 on the endothelial surface and present data that PfEMP1 is an important target for vaccine development. The immunization induced a high level of protection against the homologous strain. Protection correlated with the titer of agglutinating antibodies and occurred despite the expression of variant copies of the gene during recurrent waves of parasitemia. A second challenge with a different P. falciparum strain, to which there was no agglutinating activity, showed no protection but boosted the immune response to this region during the infection. The level of protection and the evidence of boosting during infection encourage further exploration of this concept for malaria vaccine development.
    Type of Medium: Online Resource
    ISSN: 0027-8424 , 1091-6490
    RVK:
    RVK:
    Language: English
    Publisher: Proceedings of the National Academy of Sciences
    Publication Date: 2002
    detail.hit.zdb_id: 209104-5
    detail.hit.zdb_id: 1461794-8
    SSG: 11
    SSG: 12
    Location Call Number Limitation Availability
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  • 20
    Online Resource
    Online Resource
    Proceedings of the National Academy of Sciences ; 2002
    In:  Proceedings of the National Academy of Sciences Vol. 99, No. 21 ( 2002-10-15), p. 13873-13877
    In: Proceedings of the National Academy of Sciences, Proceedings of the National Academy of Sciences, Vol. 99, No. 21 ( 2002-10-15), p. 13873-13877
    Abstract: Acute pharmacological blockade of α1 adrenoreceptors (ARs) attenuates the locomotor response to amphetamine (LRA). We took a genetic approach to study how norepinephrine (NE) signaling modulates psychostimulant responses by testing LRA in dopamine β-hydroxylase knockout ( Dbh −/−) mice that lack NE. Surprisingly, Dbh −/− animals were hypersensitive to the behavioral effects of amphetamine. Amphetamine (2 mg/kg) elicited greater locomotor activity in Dbh −/− mice compared to controls, whereas 5 mg/kg caused stereotypy in Dbh −/− mice, which is only observed in control mice at higher doses. Prazosin, an α1AR antagonist, attenuated LRA in Dbh +/− mice but had no effect in Dbh −/− mice. Changes in the sensitivity of dopamine (DA)-signaling pathways may contribute to the altered amphetamine responses of Dbh −/− mice because they were relatively insensitive to a D1 agonist and hypersensitive to a D2 agonist. Daily amphetamine administration resulted in behavioral sensitization in both Dbh +/− and Dbh −/− mice, demonstrating that NE is not required for the development or expression of behavioral sensitization. Daily prazosin administration blunted but did not completely block locomotor sensitization in Dbh +/− mice, suggesting that α1AR signaling contributes to, but is not required for sensitization in Dbh +/− control animals. We conclude that in contrast to acute α1AR blockade, chronic NE deficiency induces changes similar to sensitization, perhaps by altering DA-signaling pathways.
    Type of Medium: Online Resource
    ISSN: 0027-8424 , 1091-6490
    RVK:
    RVK:
    Language: English
    Publisher: Proceedings of the National Academy of Sciences
    Publication Date: 2002
    detail.hit.zdb_id: 209104-5
    detail.hit.zdb_id: 1461794-8
    SSG: 11
    SSG: 12
    Location Call Number Limitation Availability
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