Search Results - (Author, Cooperation:C. Shaw)

2018-03-28

The American Society for Microbiology (ASM)

0066-4804

1098-6596

Biology

Medicine

2011-11-05

American Association for the Advancement of Science (AAAS)

0036-8075

1095-9203

Biology

Chemistry and Pharmacology

Computer Science

Medicine

Natural Sciences in General

Physics

Animals ; Ataxin-1 ; Ataxins ; Cerebellum/metabolism ; Disease Models, Animal ; *Exercise Therapy ; Gene Knock-In Techniques ; Mice ; Mice, Inbred C57BL ; Mice, Mutant Strains ; Nerve Tissue Proteins/genetics ; Nuclear Proteins/genetics ; Repressor Proteins/genetics/*physiology ; Spinocerebellar Ataxias/genetics/*therapy

2018-03-06

The American Association for Cancer Research (AACR)

1078-0432

1557-3265

Medicine

2016-04-23

American Association for the Advancement of Science (AAAS)

0036-8075

1095-9203

Biology

Chemistry and Pharmacology

Computer Science

Medicine

Natural Sciences in General

Physics

Adaptor Proteins, Signal Transducing/genetics/metabolism ; Adult ; Aged ; Aged, 80 and over ; Animals ; Bacterial Infections/etiology/*immunology ; Caspase 1/metabolism ; Caspases/metabolism ; Female ; Humans ; Immunity, Innate/genetics/*immunology ; Influenza A virus/*immunology ; Influenza, Human/complications/*immunology ; Interferon-beta/immunology ; Male ; Membrane Glycoproteins/genetics/metabolism ; Mice ; Monocytes/immunology ; Myxovirus Resistance Proteins/genetics/*physiology ; Neutrophils/immunology ; Orthomyxoviridae Infections/*immunology ; Respiratory Tract Infections/*immunology/microbiology ; Toll-Like Receptor 7/genetics/metabolism ; Viral Load ; Young Adult

0307-1847

Political Science

1365-2958

Blackwell Publishing Journal Backfiles 1879-2005

Biology

Medicine

Octopine and nopaline Ti-plasmids confer upon Agrobacterium tumefaciens C58C1 the ability to respond chemotactically to the vir-inducing phenolic wound exudate, acetosyringone. A. tumefaciens C58C1 containing Ti-plasmids with Tn5 insertions in virB, C., D or E exhibited marked chemotaxis towards acetosyringone. However, Ti-plasmids with mutations in virA or VirG were unable to confer the responsive phenotype. Of the cosmid clones pVK219 (virAB) pVK221 (virBGC) pVK225 (virGCDE) and pVK257 (virABGC) mobilized to cured A. tumefaciens C58C1, only pVK257 bestowed acetosyringone chemotaxis. virA and virG are thus required for chemotaxis of A. tumefaciens towards acetosyringone. This suggests a multifunctional role for virA and virG: at low concentrations of acetosyringone they mediate chemotaxis and at higher concentrations they effect vir-induction.

Electronic Resource

2018-12-20

American Association for the Advancement of Science (AAAS)

2375-2548

Natural Sciences in General

1089-7690

AIP Digital Archive

Physics

Chemistry and Pharmacology

Electron-spin-resonance spectroscopy has been used to study the structure of radiation-induced defects in a barium galliosilicate glass compositional series of BaO/Ga2O3=1.0 and 20–80 mol % SiO2. Spin-Hamiltonian parameters derived from computer line-shape simulations have been used to identify three oxygen-associated hole centers: a gallium-oxygen hole center and two variations of silicon-oxygen hole centers. Each of these defects contains an unpaired electron in a nonbonding oxygen p orbital. The compositional dependence of the ESR data is consistent with a gradual change from a Ga-based tetrahedral network to a Si-based tetrahedral network as the silica content is increased.

Electronic Resource

1471-4159

Blackwell Publishing Journal Backfiles 1879-2005

Medicine

The factors responsible for ALS-parkinsonism dementia complex (ALS-PDC), the unique neurological disorder of Guam, remain unresolved, but identification of causal factors could lead to clues for related neurodegenerative disorders elsewhere. Earlier studies focused on the consumption and toxicity of the seed of Cycas circinalis, a traditional staple of the indigenous diet, but found no convincing evidence for toxin-linked neurodegeneration. We have reassessed the issue in a series of in vitro bioassays designed to isolate non-water soluble compounds from washed cycad flour and have identified three sterol β-d-glucosides as potential neurotoxins. These compounds give depolarizing field potentials in cortical slices, induce alterations in the activity of specific protein kinases, and cause release of glutamate. They are also highly toxic, leading to release of lactate dehydrogenase (LDH). Theaglycone form, however, is non-toxic. NMDA receptor antagonists block the actions of the sterol glucosides, but do not compete for binding to the NMDA receptor. The most probable mechanism leading to cell death may involve glutamate neuro/excitotoxicity. Mice fed cycad seed flour containing the isolated sterol glucosides show behavioral and neuropathological outcomes, including increased TdT-mediated biotin–dUTP nick-end labelling (TUNEL) positivity in various CNS regions. Astrocytes in culture showed increased caspase-3 labeling after exposure to sterol glucosides. The present results support the hypothesis that cycad consumption may be an important factor in the etiology of ALS-PDC and further suggest that some sterol glucosides may be involved in other neurodegenerative disorders.

Electronic Resource

1471-4159

Blackwell Publishing Journal Backfiles 1879-2005

Medicine

Abstract: Amyotrophic lateral sclerosis (ALS) is a human neurodegenerative disorder of unknown origin that is characterized by progressive degeneration of corticospinal tracts and anterior horn cells in the brainstem and spinal cord. Previous studies have indicated that motoneuron degeneration associated with ALS may be triggered by mechanisms leading to increased intracellular Ca2+. In the present report, Ca2+-activated phospholipid-dependent protein kinase C (PKC) was evaluated in cervical spinal cords from ALS patients and control subjects. In patients who died with ALS, PKC histone H1 phosphotransferase activity was significantly increased by 330% in cytosolic- and 118% in particulate-derived extracts compared with controls. This increase in PKC phosphotransferase activity appeared to be partially due to an increase in the amount of PKC protein present in ALS spinal cord tissue. PKC histone H1 phosphotransferase activities of cytosolic- and particulate-derived extracts from motor and visual cortex of ALS patients and controls were not statistically different, nor were there differences in PKC histone H1 phosphotransferase activity in platelets and leukocytes. The specific nature of PKC alterations in affected regions of the CNS supports a role for PKC in the events leading to motoneuron death in sporadic ALS.

Electronic Resource

1471-4159

Blackwell Publishing Journal Backfiles 1879-2005

Medicine

Abstract: Tachykinin immunoreactivity has been quantified and characterized in extracts of bovine retinae by combining radioimmunoassay, gel permeation chromatography, and reverse-phase HPLC. Using an antiserum specific for the C-terminal hexapeptide amide of substance P, levels of 3.43 ± 0.33 ng g−1 and 12.45 ± 0.76 ng g−1 (mean ± SD, n = 5) were measured in extracts prepared by acidified ethanol and boiling 0.5 M acetic acid, respectively. Levels of neurokinin A immunoreactivity, assayed using an antiserum cross-reacting with neurokinin A (100%), neurokinin B (50%), neuropeptide K (85%), and substance P (〈0.1%) were 12.46 ± 0.47 ng g−1 and 7.20 ± 0.37 ng g−1 in the same extracts. Gel permeation chromatography identified a single substance P immunoreactant eluting with substance P standard, whereas two neurokinin A immunoreactants were resolved eluting with neuropeptide K and neurokinin A standards. Reverse-phase HPLC analysis resolved immunoreactivity eluting with substance P, neurokinin A, neuropeptide K, and neurokinin B and their respective methionine sulphoxides. The amount of immunoreactive material co-eluting with the respective sulphoxides was higher in acidified ethanol extracts, and sub stance P was most susceptible to oxidative modification. Subsequent incubation of synthetic substance P with dispersed bovine retinal cells resulted in rapid conversion to three metabolites identified and isolated by reverse-phase HPLC. Each had an amino acid composition identical to that of substance P, and the major product had the same retention time as substance P sulphoxide. Deamidation was ruled out on the basis of the unequivocal demonstration of both glutamine residues and a methionine amide residue on each metabolite. These data demonstrate the presence of the mammalian tachykinins substance P, neurokinin A, neurokinin B, and neuropeptide K in the bovine retina. The susceptibility of substance P to methionine oxidation has been confirmed by incubation with dispersed retinal cells, and this putative inactivation system may be of physiological relevance within the retina.

Electronic Resource

1471-4159

Blackwell Publishing Journal Backfiles 1879-2005

Medicine

Abstract: The primary structure of gastrin-releasing peptide from the guinea pig stomach has been determined by automated Edman degradation and shown to be identical to porcine gastrin-releasing peptide. Extracts of guinea pig brain and small intestine contained both gastrin-releasing peptide and its COOH-terminal decapeptide (neuromedin C) but the stomach extracts contained only gastrin-releasing peptide. Within the small intestine, highest concentrations of gastrin-releasing peptide-like immunoreactivity were found in extracts of the circular and longitudinal smooth muscle layers.

Electronic Resource

1471-4159

Blackwell Publishing Journal Backfiles 1879-2005

Medicine

Abstract : The tripeptide glutathione (GSH) has been thoroughly investigated in relation to its role as antioxidant and free radical scavenger. In recent years, novel actions of GSH in the nervous system have also been described, suggesting that GSH may serve additionally both as a neuromodulator and as a neurotransmitter. In the present article, we describe our studies to explore further a potential role of GSH as neuromodulator/neurotransmitter. These studies have used a combination of methods, including radioligand binding, synaptic release and uptake assays, and electrophysiological recording. We report here the characteristics of GSH binding sites, the interrelationship of GSH with the NMDA receptor, and the effects of GSH on neural activity. Our results demonstrate that GSH binds via its γ-glutamyl moiety to ionotropic glutamate receptors. At micromolar concentrations GSH displaces excitatory agonists, acting to halt their physiological actions on target neurons. At millimolar concentrations, GSH, acting through its free cysteinyl thiol group, modulates the redox site of NMDA receptors. As such modulation has been shown to increase NMDA receptor channel currents, this action may play a significant role in normal and abnormal synaptic activity. In addition, GSH in the nanomolar to micromolar range binds to at least two populations of binding sites that appear to be distinct from all known excitatory amino acid receptor subtypes. GSH bound to these sites is not displaceable by glutamatergic agonists or antagonists. These binding sites, which we believe to be distinct receptor populations, appear to recognize the cysteinyl moiety of the GSH molecule. Like NMDA receptors, the GSH binding sites possess a coagonist site(s) for allosteric modulation. Furthermore, they appear to be linked to sodium ionophores, an interpretation supported by field potential recordings in rat cerebral cortex that reveal a dose-dependent depolarization to applied GSH that is blocked by the absence of sodium but not by lowering calcium or by NMDA or (S)-2-amino-3-hydroxy-5-methyl-4-isoxazolepropionate antagonists. The present data support a reevaluation of the role of GSH in the nervous system in which GSH may be involved both directly and indirectly in synaptic transmission. A full accounting of the actions of GSH may lead to more comprehensive understanding of synaptic function in normal and disease states.

Electronic Resource

1365-2133

Blackwell Publishing Journal Backfiles 1879-2005

Medicine

As a first line of defence, the skin is equipped with a complex and interactive nerve fibre system to detect irritants and maintain homeostasis. The dermal component of this fibre network has been well characterized and fibres are known to extend throughout the viable epidermis as free nerve endings. To date, this epidermal component remains poorly characterized. We have visualized human volar forearm epidermal nerve fibres by laser-scanning confocal microscopy using the pan-neuronal marker, protein gene-product 9.5 and specific antibodies to substance P, calcitonin gene-related peptide and nerve growth factor. In addition to the varicose free nerve endings, there is a 3-D fibre network in normal human epidermis, with frequent branching of fibres. Branching can be seen to converge on a central trunk apparently extending to the dermis. Thin unmyelinated fibres can be seen in all layers of the viable epidermis. Substance P staining is rarely observed and is much less intense than the protein gene-product 9.5 staining. Calcitonin gene-related peptide and nerve growth factor were not detected in volar forearm epidermis by this method.Pretreatment of the skin in vivo with the neuropharmacological agent, capsaicin, resulted in loss of epidermal fibre staining indicating that these are sensory fibres of the primary C-afferent type. Epidermal innervation in racial and ethnic skin types was also assessed. No apparent difference in innervation was observed between European caucasian and Japanese/Chinese skin at the architectural or biochemical level, i.e. the presence, properties and biochemical content of fibres was similar in all cases tested.

Electronic Resource

1365-2230

Blackwell Publishing Journal Backfiles 1879-2005

Medicine

In this study radioimmunoassay was used to determine neuropeptide levels in extracts from 17 differing anatomical regions of human skin. Marked regional variations of neuropeptide content for human skin were found and these variations are likely to reflect true physiological functions for the neuropeptides studied. In general the tachykinins, substance P (SP), neurokinin A (NKLA) and calcitonin gene-related peptide (CGRP) were found in highest concentrations in regions of skin with the greatest tactile sensation. By contrast, highest concentrations of vasoactive intestinal peptide (VIP) and peptide histidine methionine (PHM) were found in axillary skin, where they probably play a part in axillary eccrine sweat production. Neurotensin was not found in any of the skin areas sampled, suggesting that it is relatively unimportant in human physiological skin control.Reverse-phase high-performance liquid chromatography (rpHPLC) was used to verify the results of radioimmunoassay. Both SP and NKA occurred in several regions in both their reduced and oxidized forms, as well as displaying molecular heterogeneity. CGRP occurred as one molecular species, this being α-CGRP, suggesting that this is the predominant molecular form in human skin. Likewise, both VIP and PHM displayed molecular homogeneity in the regions investigated by rpHPLC.

Electronic Resource

1077-3118

AIP Digital Archive

Physics

Electronic Resource

1077-3118

AIP Digital Archive

Physics

A neodymium-doped single-mode fiber emits light at 496 and 633 nm, as well as at several near-infrared wavelengths, when pumped by a mode-locked, Q-switched Nd:YAG laser operating at 1064 nm. A threshold peak pumping power of approximately 50 kW is required for the process; peak emitted powers of several watts were observed. The blue line is more than 15 nm wide at high pumping levels and possesses large temporal pulse dispersion across its spectrum. Amplified spontaneous emission via a three-photon pumping process is proposed to account for the phenomenon.

Electronic Resource

1089-7550

AIP Digital Archive

Physics

Time domain spectroscopy has been used to measure the room temperature transmission of highly doped GaAs in the frequency range from 0.2 to above 3 THz. We studied n- and p-type layers, with carrier densities between 1016 and 2×1018 cm−3, which had been grown on undoped GaAs substrates. Transmission spectra could be fitted within experimental error by using a Drude model for the conductivity. Fitted carrier densities for both carrier types and mobilities for p-type GaAs were in good agreement with the results of Hall measurements. In the case of n-GaAs, the optically determined mobility appeared to underestimate slightly the Hall mobility. © 2000 American Institute of Physics.

Electronic Resource

1077-3118

AIP Digital Archive

Physics

The emission and detection efficiencies of photoconducting THz transmitters and receivers are found to be sensitive to the polarization of the optical gating pulse. Signal amplitudes from GaAs coplanar stripline transmitters and silicon-on-sapphire dipole receivers vary by factors of up to 4 and 3, respectively, with rotation of the exciting pulse polarization. In both cases, maximum signal is obtained when the polarization of the normally incident light is perpendicular to the edge of the metal electrodes. This polarization sensitivity, which appears to arise from differences in the spatial distribution of photoexcited carriers in the semiconductor, needs to be considered when optimizing the signal-to-noise ratio in coherent THz spectroscopy. © 1998 American Institute of Physics.

Electronic Resource

1077-3118

AIP Digital Archive

Physics

We have demonstrated the excitation and control of coherent cyclotron emission from a semiconductor using a THz beam containing pairs of sub-picosecond electric field pulses closely spaced in time. The source of THz radiation in these experiments is a biased coplanar stripline fabricated on semi-insulating GaAs and edge illuminated with pairs of temporally and spatially separated 70 fs pulses of near infrared light. A GaAs/AlGaAs two-dimensional electron gas was used in the experiments because of its long intraband phase relaxation time. Changes in the amplitude and phase of the cyclotron emission are observed when varying the interpulse delay and are well described within the theoretical framework of a two level system. © 1997 American Institute of Physics.

Electronic Resource