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71.
A novel approach to the treatment of osteoporosis in men, and possibly women, is the development of selective androgen receptor modulators (SARMs) that can stimulate formation of new bone with substantially diminished proliferative activity in the prostate, as well as reduced virilizing activity in women. Over the last several years, we have developed a program to discover and develop novel, non-steroidal, orally-active selective androgen receptor modulators (SARMs) that provide improved therapeutic benefits and reduce risk and side effects. In recent studies, we have used a skeletally mature orchiectomized (ORX) male rat as an animal model of male hypogonadism for assessing the efficacy of LGD2226, a nonsteroidal, non-aromatizable, and non-5alpha-reducible SARM. We assessed the activity of LGD2226 on bone turnover, bone mass and bone strength, and also evaluated the effects exerted on classic androgen-dependent targets, such as prostate, seminal vesicles and muscle. A substantial loss of bone density was observed in ORX animals, and this loss was prevented by SARMs, as well as standard androgens. Biochemical markers of bone turnover revealed an early increase of bone resorption in androgen-deficient rats that was repressed in ORX animals treated with the oral SARM, LGD2226, during a 4-month treatment period. Differences in architectural properties and bone strength were detected by histomorphometric and mechanical analyses, demonstrating beneficial effects of LGD2226 on bone quality in androgen-deficient rats. Histomorphometric analysis of cortical bone revealed distinct anabolic activity of LGD2226 in periosteal bone. LGD2226 was able to prevent bone loss and maintain bone quality in ORX rats by stimulating bone formation, while also inhibiting bone turnover. LGD2226 also exerted anabolic activity on the levator ani muscle. Taken together, these results suggest that orally-active, non-steroidal SARMs may be useful therapeutics for both muscle and bone in elderly hypogonadal men through their anabolic activities. Since SARMs both prevent bone loss, and also stimulate formation of new bone, they may have significant advantages relative to currently used anti-resorptive therapies. Coupled with their activity in muscle and their ability to maintain or restore libido, they offer new therapeutic approaches for male and female hormone replacement. 相似文献
72.
Systematics,morphology and biological control 总被引:2,自引:0,他引:2
Accurate systematics is the foundation on which all meaningful research in biology is based. The importance of sound systematics to practical biological control is illustrated by results from several projects on biological control of coccid pests. Correct identification of the pest species or their natural enemies, and recognition of cryptic species or infraspecific entities, have been of utmost importance to the success of many projects. Accurate morphology is the basis of reliable systematics. Unfortunately, basic morphology of the parasitic Hymenoptera is still imperfectly understood and that which is known often is inadequately used. The scanning electron microscope is a valuable tool for comparative morphological research that will go far toward solving these problems. The taxonomic validity of morphological characters, and the extent of intraspecific variation, should be determined by a detailed biometrical study of large series of cultured specimens whenever possible. This approach is illustrated with results obtained in our recent revision of the species ofAphytis, important parasites of diaspine scale insects. Comparative morphology of developmental stages of parasitic Hymenoptera is recognized as an important approach to the study of cryptic species needing much more emphasis. 相似文献
73.
74.
AMPA receptor-dependent clustering of synaptic NMDA receptors is mediated by Stargazin and NR2A/B in spinal neurons and hippocampal interneurons 总被引:3,自引:0,他引:3
Mi R Sia GM Rosen K Tang X Moghekar A Black JL McEnery M Huganir RL O'Brien RJ 《Neuron》2004,44(2):335-349
Under standard conditions, cultured ventral spinal neurons cluster AMPA- but not NMDA-type glutamate receptors at excitatory synapses on their dendritic shafts in spite of abundant expression of the ubiquitous NMDA receptor subunit NR1. We demonstrate here that the NMDA receptor subunits NR2A and NR2B are not routinely expressed in cultured spinal neurons and that transfection with NR2A or NR2B reconstitutes the synaptic targeting of NMDA receptors and confers on exogenous application of the immediate early gene product Narp the ability to cluster both AMPA and NMDA receptors. The use of dominant-negative mutants of GluR2 further showed that the synaptic targeting of NMDA receptors is dependent on the presence of synaptic AMPA receptors and that synaptic AMPA and NMDA receptors are linked by Stargazin and a MAGUK protein. This system of AMPA receptor-dependent synaptic NMDA receptor localization was preserved in hippocampal interneurons but reversed in hippocampal pyramidal neurons. 相似文献
75.
Wei Cao Li Zhang David B Rosen Laura Bover Gokuran Watanabe Musheng Bao Lewis L Lanier Yong-Jun Liu 《PLoS biology》2007,5(10)
Dendritic cells are equipped with lectin receptors to sense the extracellular environment and modulate cellular responses. Human plasmacytoid dendritic cells (pDCs) uniquely express blood dendritic cell antigen 2 (BDCA2) protein, a C-type lectin lacking an identifiable signaling motif. We demonstrate here that BDCA2 forms a complex with the transmembrane adapter FcɛRIγ. Through pathway analysis, we identified a comprehensive signaling machinery in human pDCs, similar to that which operates downstream of the B cell receptor (BCR), which is distinct from the system involved in T cell receptor (TCR) signaling. BDCA2 crosslinking resulted in the activation of the BCR-like cascade, which potently suppressed the ability of pDCs to produce type I interferon and other cytokines in response to Toll-like receptor ligands. Therefore, by associating with FcɛRIγ, BDCA2 activates a novel BCR-like signaling pathway to regulate the immune functions of pDCs. 相似文献
76.
Robert Rosen 《Bulletin of mathematical biology》1964,26(2):103-111
It is shown that a rather close relationship exists between the (ℳ,ℛ)-systems, defined previously as prototypes of abstract
biological systems, and the sequential machines which have been studied by various authors. The theory of sequential machines
is reformulated in a way suitable for its application to the study of the intertransformability of (ℳ,ℛ)-systems as a result
of environmental alteration. The important concept of strong connectedness is most useful in this direction, and is used to
derive a number of results on intertransformability. Some suggestions are made for further studies along these lines. 相似文献
77.
78.
79.
Maurice Ogur Ralph O. Erickson Gloria U. Rosen Katharine B. Sax Constance Holden 《Experimental cell research》1951,2(1):73-89
Methods are described for preparing cell suspensions of Lilium microsporocytes, microspores and pollen grains; for obtaining cell counts of these suspensions; and for their analysis for pentose nucleic acid (PNA) and desoxypentose nucleic acid (DNA).The results of these analyses have been calculated to nucleic acid content in μμg per microsporocyte, microspore or pollen grain, and the results related to logarithm of flower bud length, an index of the developmental status of the cells, and of their temporal relationship to meiosis, microspore mitosis and opening of the flower.DNA content per cell drops sharply at the end of meiosis, with the formation of four microspores from each microsporocyte. It then increases gradually during the microspore interphase between meiosis and the microspore mitosis. At microspore mitosis DNA content doubles rapidly. In the development of the resulting binucleate pollen grain, from microspore mitosis until the opening of the flower, there is a further gradual increase of DNA content. PNA content of these cells follows the same pattern up to microspore mitosis at a level about twice that of DNA, increases sharply at mitosis, and continues to increase rapidly at a rate nine times that for DNA in the maturing pollen grain.The absolute amounts of DNA and PNA are great. At the time of anthesis the two-celled pollen grain contains about 375 μμg of DNA and 1705 μμg of PNA. 相似文献
80.
Robert Rosen 《Bulletin of mathematical biology》1958,20(3):245-260
The relational phenomena exhibited by metabolizing systems may be considered as special cases of those exhibited by a more
general class of systems. This class is specified, and some of tis properties developed. An attempt is then made to apply
these properties to a theory of metabolism by suitable specialization. A number of biologically significant theorems are obtained
which apply directly to the theory of the free-living single cell. Among the results obtained are the following: On the basis
of our model, there must always exist a component of the system which cannot be replaced or repaired by the system in the
event of its inhibition or destruction. Under certain conditions, a metabolizing system possesses a component the inhibition
of which will completely terminate the metabolic activity of the system. Furthermore a number of other diverse phenomena,
such as the effects of a deficient environment, encystment phenomena, and even an indication of why a metabolizing system
which represents a cell should possess a nucleus, follow in a straightforward fashion from our model. 相似文献