Sirtuin 2 inhibitors rescue alpha-synuclein-mediated toxicity in models of Parkinson's disease     

Outeiro TF  Kontopoulos E  Altmann SM  Kufareva I  Strathearn KE  Amore AM  Volk CB  Maxwell MM  Rochet JC  McLean PJ  Young AB  Abagyan R  Feany MB  Hyman BT  Kazantsev AG 《Science (New York, N.Y.)》2007,317(5837):516-519

The sirtuins are members of the histone deacetylase family of proteins that participate in a variety of cellular functions and play a role in aging. We identified a potent inhibitor of sirtuin 2 (SIRT2) and found that inhibition of SIRT2 rescued alpha-synuclein toxicity and modified inclusion morphology in a cellular model of Parkinson's disease. Genetic inhibition of SIRT2 via small interfering RNA similarly rescued alpha-synuclein toxicity. Furthermore, the inhibitors protected against dopaminergic cell death both in vitro and in a Drosophila model of Parkinson's disease. The results suggest a link between neurodegeneration and aging.  相似文献   

Genetic ablation: targeted expression of a toxin gene causes microphthalmia in transgenic mice   总被引：25，自引：0，他引：25  

M L Breitman  S Clapoff  J Rossant  L C Tsui  L M Glode  I H Maxwell  A Bernstein 《Science (New York, N.Y.)》1987,238(4833):1563-1565

Lineage-specific regulatory elements can be used to direct expression of a variety of genes to specific tissues in transgenic mice. If the hybrid constructs contain a gene encoding a cytotoxic gene product, then genetic ablation of a specific cell lineage can be achieved. We have generated six transgenic mice by introducing into fertilized eggs the mouse gamma 2-crystallin promoter fused to the coding region of the diphtheria toxin A-chain gene. Three of these mice and all the transgenic offspring analyzed were microphthalmic. The lenses of these mice displayed considerable heterogeneity: some were almost normal morphologically but reduced in size, whereas others were grossly aberrant and deficient in nuclear fiber cells. These studies indicate that programmed ablation of specific cell types can be stably transmitted through the germ line.  相似文献   

The sea and its resources     

Maxwell AE 《Science (New York, N.Y.)》1973,179(4077):1021-1022

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Chemical composition of lunar material     

Maxwell JA  Abbey S  Champ WH 《Science (New York, N.Y.)》1970,167(3918):530-531

Chemical and emission spectrographic analyses of three Apollo 11 samples, 10017-29, 10020-30, and 10084-132, are given. Major and minor constituents were determined both by conventional rock analysis methods and by a new composite scheme utilizing a lithium fluoborate method for dissolution of the samples and atomic absorption spectroscopy and colorimetry. Trace constituents were determined by optical emission spectroscopy involving a d-c arc, air-jet controlled.  相似文献   

A fluoroquinolone resistance protein from Mycobacterium tuberculosis that mimics DNA     

Hegde SS  Vetting MW  Roderick SL  Mitchenall LA  Maxwell A  Takiff HE  Blanchard JS 《Science (New York, N.Y.)》2005,308(5727):1480-1483

Fluoroquinolones are gaining increasing importance in the treatment of tuberculosis. The expression of MfpA, a member of the pentapeptide repeat family of proteins from Mycobacterium tuberculosis, causes resistance to ciprofloxacin and sparfloxacin. This protein binds to DNA gyrase and inhibits its activity. Its three-dimensional structure reveals a fold, which we have named the right-handed quadrilateral beta helix, that exhibits size, shape, and electrostatic similarity to B-form DNA. This represents a form of DNA mimicry and explains both its inhibitory effect on DNA gyrase and fluoroquinolone resistance resulting from the protein's expression in vivo.  相似文献   

Rise and fall of species occupancy in Cenozoic fossil mollusks     

Foote M  Crampton JS  Beu AG  Marshall BA  Cooper RA  Maxwell PA  Matcham I 《Science (New York, N.Y.)》2007,318(5853):1131-1134

In the time between speciation and extinction, a species' ecological and biogeographic footprint-its occupancy-will vary in response to macroecological drivers and historical contingencies. Despite their importance for understanding macroecological processes, general patterns of long-term species occupancy remain largely unknown. We documented the occupancy histories of Cenozoic marine mollusks from New Zealand. For both genera and species, these show a distinct pattern of increase to relatively short-lived peak occupancy at mid-duration, followed by a decline toward extinction. Thus, species at greatest risk for extinction are those that have already been in decline for a substantial period of time. This pattern of protracted rise and fall stands in contrast to that of incumbency, insofar as species show no general tendency to stay near maximal occupancy once established.  相似文献   

Method for the detection of synthetic cry3A in transgenic potatoes     

Smith DS  Maxwell PW  De Boer SH 《Journal of agricultural and food chemistry》2004,52(4):809-815

All transgenic cultivars of potatoes registered in Canada and the United States have been modified to express a synthetic cry3A gene as a means of conferring resistance against the Colorado potato beetle, an important economic pest of potatoes. A PCR method was developed to amplify a 499 bp region of the synthetic cry3A gene. Using this method, synthetic cry3A could be detected in six different transgenic cultivars. Positive results could be confirmed with PvuII restriction digestion of the PCR-generated amplicon, which resulted in two fragments that were 283 and 216 bp in size. Of the 52 tuber extracts tested with this method, no false positive or false negative results were obtained, suggesting the method could be used with a high degree of accuracy. The absolute limit of detection was the number of cry3A copies present in one or perhaps two haploid copies of the potato genome. The practical limit of detection in tubers on a fresh weight basis was 0.02% for the NL 10-SUP and 0.01% for the remaining cultivars. Synthetic cry3A could also be detected in processed food products such as potato chips, shoestring potatoes, and frozen French fries. The method was suitable for screening potato tuber lots and some processed foods for the presence of synthetic cry3A.  相似文献   

Studies of parvovirus vaccination in the dog: the performance of live attenuated feline parvovirus vaccines     

H Thompson  I A McCandlish  H J Cornwell  L Macartney  N S Maxwell  A F Weipers  I R Wills  J A Black  A C Mackenzie 《The Veterinary record》1988,122(16):378-385

The performance of three live attenuated feline parvovirus vaccines licensed for use in the dog was studied. At the end of the primary vaccination course 67 per cent of dogs had inadequate antibody levels (less than or equal to 32) as measured by a haemagglutination inhibition test. Interference by maternal antibody accounted for some of the failures but the fact that there was no significant difference in performance between dogs vaccinated at 12 weeks or 16 weeks of age indicated that maternal antibody was not the only factor.  相似文献   

SELENIUM AND EWE INFERTILITY IN WESTERN AUSTRALIA     

J. A. L. Maxwell  B.V.Sc. 《Australian veterinary journal》1972,48(11):598-600

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Ultrastructural study of the liver and kidney in ochratoxicosis A in young broiler chicks   总被引：1，自引：0，他引：1  

P Dwivedi  R B Burns  M H Maxwell 《Research in veterinary science》1984,36(1):104-116

Ultrastructural changes are reported in the kidney and liver of 20-day-old broiler chicks fed ochratoxin A (OA), incorporated in the diet at levels of 2 and 4 ppm. Changes in the kidney included the presence of abnormally shaped mitochondria in the proximal convoluted tubules. There was an increase in the size and number of mitochondrial dense granules and cytoplasmic peroxisomes. Intranuclear and cytoplasmic lipid droplets and electron dense round bodies in the dilated smooth endoplasmic reticulum were also noted. Regional thickening and degeneration of the glomerular basement membrane was observed in some cases. In the liver from OA fed birds there was an increased accumulation of cytoplasmic glycogen in the hepatocytes. Abnormal mitochondrial ring forms in the kidney and the accumulation of glycogen in the liver are considered to be of diagnostic significance in ochratoxicosis of young broiler chicks. The severity of the changes was found to be dose related. These results suggest that the mitochondria in the proximal convoluted tubules of kidney were most sensitive to OA toxicity.  相似文献