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991.
Henry Brodaty Philip Mitchell Georgina Luscombe John B. Kwok Renee F. Badenhop Rod McKenzie Peter R. Schofield 《Human genetics》2002,110(1):8-14
Idiopathic basal ganglia calcification (IBGC) is characterised by radiological, neurological, cognitive and psychiatric abnormalities. The associations between these abnormal phenotypes and abnormal genes remain unclear despite the recent mapping to chromosome 14q of a susceptibility locus for IBGC ( IBGC1). We identified two siblings, from a large multigenerational pedigree, who had both been diagnosed with radiological IBGC, dementia, bipolar affective disorder and Parkinsonism. We assessed (1) other family members to determine whether these four phenotypes were co-segregating as symptoms of IBGC, and (2) possible IBGC linkage to the IBGC1 locus on chromosome 14q or to any known or potential dementia genes. Nine second-generation and 21 third-generation members received radiological, neurological, neuropsychological and psychiatric assessments. We genotyped all family members for microsatellite markers at the IBGC1 locus and polymorphisms of the ApoE, VLDL, alpha1-ACT, BChE-K, APP, PS1, PS2 and tau genes and tested these for linkage to IBGC, dementia and bipolar disorder. Of the ten family members with radiological intracranial calcification, all except the two index cases were normal. There was no significant association between IBGC status and severe cognitive impairment or dementia ( P=0.335) or bipolar affective disorder or Parkinsonism ( P=1.0). Linkage to the IBGC1 locus was excluded. Of the eight dementia gene markers tested, the only positive LOD score was for the ApoE epsilon4 polymorphism and dementia/severe cognitive impairment. We have identified a form of IBGC in which calcification is inherited independently of neurological, cognitive and psychiatric symptoms. This may represent a second locus for this disorder. 相似文献
992.
993.
Xavier Bonnet David Pearson Mitchell Ladyman Olivier Lourdais Don Bradshaw 《Austral ecology》2002,27(4):442-450
Abstract Animals resident on small islands provide excellent opportunities to carry out detailed mark–recapture studies. Populations are closed and ecosystems are often simpler than those of mainland sites. These factors enable the study of cryptic species that have otherwise been neglected. Snakes are notable for their secretive nature and, as a result, few natural populations have been accurately described through long‐term mark–recapture monitoring. A population of tiger snakes (Notechis scutatus) was studied on Carnac Island, a small limestone island (16 ha) off the coast of Western Australia. Population estimates show that snake density is very high, with more than 20 adult snakes per ha. This equates to a biomass of more than 100 kg of a top predator concentrated in a very small area. Such a high predator density can be explained because adult snakes feed mainly on chicks of nesting birds that breed in large colonies on Carnac but forage elsewhere. Substantial annual growth rates in body size in most individuals suggest that food availability is high on Carnac. Growth rates decreased more sharply in adult females than in males, whereas annual changes in body mass were similar in both sexes, probably because of the high energetic costs of reproduction experienced by females. Surprisingly, the sex ratio was highly biased, with males largely outnumbering females. 相似文献
994.
995.
Matrix metalloproteinases are involved in C-terminal and interglobular domain processing of cartilage aggrecan in late stage cartilage degradation. 总被引:13,自引:0,他引:13
Christopher B Little Clare E Hughes Clare L Curtis Mike J Janusz Richard Bohne Sherry Wang-Weigand Yetunde O Taiwo Peter G Mitchell Ivan G Otterness Carl R Flannery Bruce Caterson 《Matrix biology》2002,21(3):271-288
Monoclonal antibody (MAb) technology was used to examine aggrecan metabolites and the role of aggrecanases and matrix metalloproteinases (MMPs) in proteolysis of the interglobular domain (IGD) and C-terminus of aggrecan. An in vitro model of progressive cartilage degradation characterized by early proteoglycan loss and late stage collagen catabolism was evaluated in conjunction with a broad-spectrum inhibitor of MMPs. We have for the first time demonstrated that IGD cleavage by MMPs occurs during this late stage cartilage degeneration, both as a primary event in association with glycosaminoglycan (GAG) release from the tissue and secondarily in trimming of aggrecanase-generated G1 metabolites. Additionally, we have shown that MMPs were responsible for C-terminal catabolism of aggrecan and generation of chondroitin sulfate (CS) deficient aggrecan monomers and that this aggrecan truncation occurred prior to detectable IGD cleavage by MMPs. The onset of this later stage MMP activity was also evident by the generation of MMP-specific link protein catabolites in this model culture system. Recombinant MMP-1, -3 and -13 were all capable of C-terminally truncating aggrecan with at least two cleavage sites N-terminal to the CS attachment domains of aggrecan. Through analysis of aggrecan metabolites in pathological synovial fluids from human, canine and equine sources, we have demonstrated the presence of aggrecan catabolites that appear to have resulted from similar C-terminal processing of aggrecan as that induced in our in vitro culture systems. Finally, by developing a new MAb recognizing a linear epitope in the IGD of aggrecan, we have identified two novel aggrecan metabolites generated by an as yet unidentified proteolytic event. Collectively, these results suggest that C-terminal processing of aggrecan by MMPs may contribute to the depletion of cartilage GAG that leads to loss of tissue function in aging and disease. Furthermore, analysis of aggrecan metabolites resulting from both C-terminal and IGD cleavage by MMPs may prove useful in monitoring different stages in the progression of cartilage degeneration. 相似文献
996.
Movement and sound generation by the toadfish swimbladder 总被引:4,自引:0,他引:4
Michael L. Fine Karl L. Malloy Charles King Steve L. Mitchell Timothy M. Cameron 《Journal of comparative physiology. A, Neuroethology, sensory, neural, and behavioral physiology》2001,187(5):371-379
Although sound-producing (sonic) muscles attached to fish swimbladders are the fastest known vertebrate muscles, the functional requirement for such extreme speed has never been addressed. We measured movement of the swimbladder caused by sonic muscle stimulation in the oyster toadfish Opsanus tau and related it to major features of the sound waveform. The movement pattern is complex and produces sound inefficiently because the sides and bottom of the bladder move in opposite in and out directions, and both movement and sound decay rapidly. Sound amplitude is related to speed of swimbladder movement, and slow movements do not produce perceptible sound. Peak sound amplitude overlaps fundamental frequencies of the male's mating call because of muscle mechanics and not the natural frequency of the bladder. These findings suggest that rapid muscle speed evolved to generate sound from an inefficient highly damped system. 相似文献
997.
Lead poisoning was produced in suckling rats by lead fed to lactating mother rats being transmitted to newborns maternal milk. The brain of 25 day old lead poisoned rats contained 6.0 to 12.5 ppm lead. Zinc was depressed 56% (cerebral cortex), 45% in cerebellum and 43% (caudate nucleus) whereas copper was depressed 52% in the cerebellum. Inhibition of monoamine oxidase (pargyline) or partial depletion of serotonin and norepinephrine did not alter the concentration of Fe, Cu, Zn, or Mn in brain. 相似文献
998.
999.
C. Shively S. Clarke N. King S. Schapiro G. Mitchell 《American journal of primatology》1982,2(4):373-384
One large social group of each of three species of macaques (Macaca mulatta, M. fascicularis, M. radiata), housed in half-acre field cages at the California Primate Research Center, were observed for a total of 150 h. Data on sexual behavior and dominance interactions were recorded by pairs of experienced observers using a focal animal technique. Single or multiple mount-to-ejaculation sequences, number of thrusts per mount, number of mounts per sequence, duration of mounts per sequence, duration of sequences, social rank and frequency of sexual activity were recorded for each adult male. M. mulatta used a multiple mount-to-ejaculation (MME) pattern in 91% of their copulations. M. radiata used a single mount-to-ejaculation (SME) pattern in 91% of their copulations. M. fascicularis used both patterns—53% MME and 47% SME. A positive correlation was found between rank and sexual activity in fascicularis and mulatta males. A negative correlation between rank and sexual activity was found in radiata males and also a positive correlation between rank and age indicating that the youngest and most subordinate radiata males were the most sexually active males. In reviewing the literature, a relationship between degree of intermale competition, intermale tolerance and type of mounting pattern was revealed. Macaque species that primarily use an SME pattern also show sa high degree of intermale tolerance and little interrnale competition. Macaque species that primarily use an MME pattern typically show a high degree of intermale competition and a low degree of intermale tolerance. Possible events leading to such relationships are discussed. 相似文献
1000.
Francisco Javier Tovar-Lopez Gary Rosengarten Mahyar Nasabi Vijay Sivan Khashayar Khoshmanesh Shaun P. Jackson Arnan Mitchell Warwick S. Nesbitt 《PloS one》2013,8(10)
This paper reports on an investigation of mass transport of blood cells at micro-scale stenosis where local strain-rate micro-gradients trigger platelet aggregation. Using a microfluidic flow focusing platform we investigate the blood flow streams that principally contribute to platelet aggregation under shear micro-gradient conditions. We demonstrate that relatively thin surface streams located at the channel wall are the primary contributor of platelets to the developing aggregate under shear gradient conditions. Furthermore we delineate a role for red blood cell hydrodynamic lift forces in driving enhanced advection of platelets to the stenosis wall and surface of developing aggregates. We show that this novel microfluidic platform can be effectively used to study the role of mass transport phenomena driving platelet recruitment and aggregate formation and believe that this approach will lead to a greater understanding of the mechanisms underlying shear-gradient dependent discoid platelet aggregation in the context of cardiovascular diseases such as acute coronary syndromes and ischemic stroke. 相似文献