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21.
The molecular mechanisms whereby volatile general anesthetics (VAs) disrupt behavior remain undefined. In Caenorhabditis elegans mutations in the gene unc-64, which encodes the presynaptic protein syntaxin 1A, produce large allele-specific differences in VA sensitivity. UNC-64 syntaxin normally functions to mediate fusion of neurotransmitter vesicles with the presynaptic membrane. The precise role of syntaxin in the VA mechanism is as yet unclear, but a variety of results suggests that a protein interacting with syntaxin to regulate neurotransmitter release is essential for VA action in C. elegans. To identify additional proteins that function with syntaxin to control neurotransmitter release and VA action, we screened for suppressors of the phenotypes produced by unc-64 reduction of function. Loss-of-function mutations in slo-1, which encodes a Ca(2+)-activated K+ channel, and in unc-43, which encodes CaM-kinase II, and a gain-of-function mutation in egl-30, which encodes Gqalpha, were isolated as syntaxin suppressors. The slo-1 and egl-30 mutations conferred resistance to VAs, but unc-43 mutations did not. The effects of slo-1 and egl-30 on VA sensitivity can be explained by their actions upstream or parallel to syntaxin to increase the level of excitatory neurotransmitter release. These results strengthen the link between transmitter release and VA action. 相似文献
22.
The skeletal remains of an infant from a southwest South African rock shelter at Byneskranskop show pervasive abnormalities that are consistent with the effects of hypertrophic (hyperplastic) rickets. Diagnostic features include beading of the costochondral junctions of the ribs, flaring and tilting of the metaphyses, and cupping of the distal ulna, as well as general skeletal hypertrophy. With an uncalibrated accelerator mass spectrometry (AMS) radiocarbon date of 4820 +/- 90 BP (TO-9531), this is a very early instance of the condition, among foragers whose environment and diet make dietary shortages of active vitamin D or dietary calcium improbable. Carbon and nitrogen stable isotope ratios indicate a mixed diet, including marine as well as terrestrial protein. Solicitous care maintained the sick infant to an estimated age of 3.5-5 months; it was buried in a manner like that of other deceased group members. This case suggests that if infanticide was practiced, it was an option only during the immediate perinatal period, when this infant would have appeared normal. This is consistent with documentation of infanticide practices among historic foragers from southern Africa. 相似文献
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Garmise RJ Mar K Crowder TM Hwang CR Ferriter M Huang J Mikszta JA Sullivan VJ Hickey AJ 《AAPS PharmSciTech》2006,7(1):E131-E137
The purpose of this research was to prepare a dry powder vaccine formulation containing whole inactivated influenza virus
(VIIV) and a mucoadhesive compound suitable for nasal delivery. Powders containing WIIV and either lactose or trehalose were
produced by lyophilization. A micro-ball mill was used to reduce the lyophilized cake to sizes suitable for nasal delivery.
Chitosan flakes were reduced in size using a cryo-milling technique. Milled powders were sieved between 45 and 125 μm aggregate
sizes and characterized for particle size and distribution, morphology, and flow properties. Powders were blended in the micro-ball
mill without the ball. Lyophilization followed by milling produced irregularly shaped, polydisperse particles with a median
primary particle diameter of ≈21 μm and a yield of ≈37% of particles in the 45 to 125 μm particle size range. Flow properties
of lactose and trehalose powders after lyophilization followed by milling and sieving were similar. Cryo-milling produced
a small yield of particles in the desired size range (<10%). Lyophilization followed by milling and sieving produced particles
suitable for nasal delivery with different physicochemical properties as a function of processing conditions and components
of the formulation. Further optimization of particle size and morphology is required for these powders to be suitable for
clinical evaluation.
Published: March 10, 2006 相似文献
25.
In an effort to biochemically characterize metallo-β-lactamase NDM-1, we cloned, overexpressed, purified, and characterized several maltose binding protein (MBP)-NDM-1 fusion proteins with different N-termini (full-length, Δ6, Δ21, and Δ36). All MBP-NDM-1 fusion proteins were soluble; however, only one, MBP-NDM-1Δ36, exhibited high activity and bound 2 equiv of Zn(II). Thrombin cleavage of this fusion protein resulted in the truncated NDM-1Δ36 variant, which exhibited a k(cat) of 16 s(-1) and a K(m) of 1.1 μM when using nitrocefin as a substrate, bound 2 equiv of Zn(II), and was monomeric in solution. Extended X-ray absorption fine structure studies of the NDM-1Δ36 variant indicate the average metal binding site for Zn(II) in this variant consists of four N/O donors (two of which are histidines) and 0.5 sulfur donor per zinc, with a Zn-Zn distance of 3.38 ?. This metal binding site is very similar to those of other metallo-β-lactamases that belong to the B1 subclass. Pre-steady-state kinetic studies using nitrocefin and chromacef and the NDM-1Δ36 variant indicate that the enzyme utilizes a kinetic mechanism similar to that used by metallo-β-lactamases L1 and CcrA, in which a reactive nitrogen anion is stabilized and its protonation is rate-limiting. While they are very different in terms of amino acid sequence, these studies demonstrate that NDM-1 is structurally and mechanistically very similar to metallo-β-lactamase CcrA. 相似文献
26.
Crowder DW Ellers-Kirk C Yafuso CM Dennehy TJ Degain BA Harpold VS Tabashnik BE Carrière Y 《Journal of economic entomology》2008,101(3):927-932
We evaluated effects of the insect growth regulator pyriproxyfen on Bemisia tabaci (Gennadius) (B biotype) (Hemiptera: Aleyrodidae) males and females in laboratory bioassays. Insects were treated with pyriproxyfen as either eggs or nymphs. In all tests, the LC50 for a laboratory-selected resistant strain was at least 620 times greater than for an unselected susceptible strain. When insects were treated as eggs, survival did not differ between males and females of either strain. When insects were treated as nymphs, survival did not differ between susceptible males and susceptible females, but resistant males had higher mortality than resistant females. The dominance of resistance decreased as pyriproxyfen concentration increased. Resistance was partially or completely dominant at the lowest concentration tested and completely recessive at the highest concentration tested. Hybrid female progeny from reciprocal crosses between the susceptible and resistant strains responded alike in bioassays; thus, maternal effects were not evident. Rapid evolution of resistance to pyriproxyfen could occur if individuals in field populations had resistance with traits similar to those of the laboratory-selected strain examined here. 相似文献
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Roots of Typha latifolia L. exposed to Fe2+ under reduced conditions in solution culture developed visible coatings (plaques) of an oxidized Fe compound that extended as much as 15-17 μm into the rhizosphere. Iron concentrations were significantly less and discoloration was not apparent on the surface of roots exposed to Fe-(BPDS)3, Fe3+, Fe-EDDHA, and Fe-EDTA. The extent of plaque formation increased with the concentration of Fe2+ in solution and with pH of the solution in the range of 3.0 to 4.6. Above pH 4.6, oxidation of Fe2+ in the culture solution may have reduced precipitation of Fe on the root surface. Plaque development was most extensive approximately 1.0 cm from the root tip, but all root surfaces showed some Fe staining. Scanning electron micrographs of plaqued roots, grown both in solution culture and in the field, provided support for a model of cast formation by oxidation and precipitation of Fe on external cell surfaces. 相似文献
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