2,173 research outputs found

    Neural correlates of processing valence and arousal in affective words

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    Psychological frameworks conceptualize emotion along 2 dimensions, "valence" and "arousal." Arousal invokes a single axis of intensity increasing from neutral to maximally arousing. Valence can be described variously as a bipolar continuum, as independent positive and negative dimensions, or as hedonic value (distance from neutral). In this study, we used functional magnetic resonance imaging to characterize neural activity correlating with arousal and with distinct models of valence during presentation of affective word stimuli. Our results extend observations in the chemosensory domain suggesting a double dissociation in which subregions of orbitofrontal cortex process valence, whereas amygdala preferentially processes arousal. In addition, our data support the physiological validity of descriptions of valence along independent axes or as absolute distance from neutral but fail to support the validity of descriptions of valence along a bipolar continuum

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    Vaccination reduces the viral load and the risk of transmission of Jembrana disease virus in Bali cattle

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    The efficacy of a tissue-derived vaccine, which is currently used in Indonesia to control the spread of Jembrana disease in Bali cattle, was determined by quantifying the viral load in plasma following experimental infection with Jembrana disease virus. Virus transmission is most likely to occur during the acute phase of infection when viral titers are greater than 106 genomes/ml. Vaccinated cattle were found to have a 96% reduction in viral load above this threshold compared to control cattle. This would reduce the chance of virus transmission as the number of days above the threshold in the vaccinated cattle was reduced by 33%. Viral loads at the onset and resolution of fever were significantly lower in the vaccinated cattle and immune function was maintained with the development of antibody responses to Env proteins within 10-24 days post challenge. There was, however, no significant reduction in the duration of the febrile period in vaccinated animals. The duration and severity of clinical parameters were found to be variable within each group of cattle but the quantification of viral load revealed the benefits of vaccinating to reduce the risk of virus transmission as well as to ameliorate disease

    Structure of d(TGCGCA)(2) and a comparison with other DNA Hexamers

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    The X-ray crystal structure of d(TGCGCA)(2) has been determined at 120 K to a resolution of 1.3 Angstrom. Hexamer duplexes, in the Z-DNA conformation, pack in an arrangement similar to the 'pure spermine form' [Egli et al. (1991). Biochemistry, 30, 11388-11402] but with significantly different cell dimensions. The phosphate backbone exists in two equally populated discrete conformations at one nucleotide step, around phosphate 11. The structure contains two ordered cobalt hexammine molecules which have roles in stabilization of both the Z-DNA conformation of the duplex and in crystal packing. A comparison of d(TGCGCA)(2) with other Z-DNA hexamer structures available in the Nucleic Acid Database illustrates the elusive nature of crystal packing. A review of the interactions with the metal cations Na+, Mg2+ and Co3+ reveals a relatively small proportion of phosphate binding and that close contacts between metal ions are common. A prediction of the water structure is compared with the observed pattern in the reported structure

    Case studies on access and benefit-sharing

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    Clinical Pharmacokinetics, Pharmacodynamics, Safety and Efficacy of Liposomal Amphotericin B

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    Item does not contain fulltextSince its introduction in the 1990s, liposomal amphotericin B (LAmB) continues to be an important agent for the treatment of invasive fungal diseases caused by a wide variety of yeasts and molds. This liposomal formulation was developed to improve the tolerability of intravenous amphotericin B, while optimizing its clinical efficacy. Since then, numerous clinical studies have been conducted, collecting a comprehensive body of evidence on its efficacy, safety, and tolerability in the preclinical and clinical setting. Nevertheless, insights into the pharmacokinetics and pharmacodynamics of LAmB continue to evolve and can be utilized to develop strategies that optimize efficacy while maintaining the compound's safety. In this article, we review the clinical pharmacokinetics, pharmacodynamics, safety, and efficacy of LAmB in a wide variety of patient populations and in different indications, and provide an assessment of areas with a need for further clinical research

    Uniaxial Phase Transition in Si : Ab initio Calculations

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    Based on a previously proposed thermodynamic analysis, we study the relative stabilities of five Si phases under uniaxial compression using ab initio methods. The five phases are diamond, beta-tin, sh, sc, and hcp structures. The possible phase-transition patterns were investigated by considering the phase transitions between any two chosen phases of the five phases. By analyzing the different conributions to the relative pahse stability, we identified the most important factors in reducing the phase-transition pressures at uniaxial compression. We also show that it is possible to have phase transitions occur only when the phases are under uniaxial compression, in spite of no phase transition when under hydrostatic commpression. Taking all five phases into consideration, the phase diagram at uniaxial compression was constructed for pressures under 20 GPa. The stable phases were found to be diamond, beta-tin and sh structures, i.e. the same as those when under hydrostatic condition. According to the phase diagram, direct phase transition from the diamond to the sh phase is possible if the applied uniaxial pressures, on increasing, satisfy the condition of Px>Pz. Simiilarly, the sh-to-beta-tin transition on increeasing pressures is also possible if the applied uniaxial pressures are varied from the condition of Px>Pz, on which the phase of sh is stable, to that of Px<Pz, on which the beta-tin is stable

    Inhibition of the norepinephrine transporter by Ο‡-conotoxin dendrimers.

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    Peptide dendrimers are a novel class of macromolecules of emerging interest with the potential of delayed renal clearance due to their molecular size and enhanced activity due to the multivalency effect. In this work, an active analogue of the disulfide-rich Ο‡-conotoxin Ο‡-MrIA (Ο‡-MrIA), a norepinephrine reuptake (norepinephrine transporter) inhibitor, was grafted onto a polylysine dendron. Dendron decoration was achieved by employing copper-catalyzed alkyne-azide cycloaddition with azido-PEG chain-modified Ο‡-MrIA analogues, leading to homogenous 4-mer and 8-mer Ο‡-MrIA dendrimers with molecular weights ranging from 8 to 22 kDa. These dendrimers were investigated for their impact on peptide secondary structure, in vitro functional activity, and potential anti-allodynia in vivo. NMR studies showed that the Ο‡-MrIA tertiary structure was maintained in the Ο‡-MrIA dendrimers. In a functional norepinephrine transporter reuptake assay, Ο‡-MrIA dendrimers showed slightly increased potency relative to the azido-PEGylated Ο‡-MrIA analogues with similar potency to the parent peptide. In contrast to Ο‡-MrIA, no anti-allodynic action was observed when the Ο‡-MrIA dendrimers were administered intrathecally in a rat model of neuropathic pain, suggesting that the larger dendrimer structures are unable to diffuse through the spinal column tissue and reach the norepinephrine transporter.NHMRC Grants: 1045964 & 107211
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