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3836 Publications

Showing 3431-3440 of 3836 results
06/01/05 | Learning in realistic networks of spiking neurons and spike-driven plastic synapses.
Mongillo G, Curti E, Romani S, Amit DJ
European Journal of Neuroscience. 2005 Jun;21(11):3143-60. doi: 10.1111/j.1460-9568.2005.04087.x

We have used simulations to study the learning dynamics of an autonomous, biologically realistic recurrent network of spiking neurons connected via plastic synapses, subjected to a stream of stimulus-delay trials, in which one of a set of stimuli is presented followed by a delay. Long-term plasticity, produced by the neural activity experienced during training, structures the network and endows it with active (working) memory, i.e. enhanced, selective delay activity for every stimulus in the training set. Short-term plasticity produces transient synaptic depression. Each stimulus used in training excites a selective subset of neurons in the network, and stimuli can share neurons (overlapping stimuli). Long-term plasticity dynamics are driven by presynaptic spikes and coincident postsynaptic depolarization; stability is ensured by a refresh mechanism. In the absence of stimulation, the acquired synaptic structure persists for a very long time. The dependence of long-term plasticity dynamics on the characteristics of the stimulus response (average emission rates, time course and synchronization), and on the single-cell emission statistics (coefficient of variation) is studied. The study clarifies the specific roles of short-term synaptic depression, NMDA receptors, stimulus representation overlaps, selective stimulation of inhibition, and spike asynchrony during stimulation. Patterns of network spiking activity before, during and after training reproduce most of the in vivo physiological observations in the literature.

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Magee Lab
06/01/05 | Plasticity of dendritic function.
Magee JC, Johnston D
Current Opinion in Neurobiology. 2005 Jun;15:334-42. doi: 10.1002/cbic.201000254

The various properties of neuronal dendrites–their morphology, active membrane and synaptic properties–all play important roles in determining the functional capabilities of central nervous system neurons. Because of their fundamental involvement in both synaptic integration and synaptic plasticity, the active dendritic properties are important for both neuronal information processing and storage. The active properties of dendrites are determined by the densities of voltage-gated ion channels located within the dendrites in addition to the biophysical characteristics of those channels. The real power of this system resides in the level of plasticity that is provided by the many forms of channel modulation known to exist in neurons. Indeed, voltage gated ion channel modulation shapes the active properties of neuronal dendrites to specific conditions, thus tailoring the functional role of the single neuron within its circuit.

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06/01/05 | Recombinant approaches to IgG-like bispecific antibodies.
Marvin JS, Zhu Z
Acta Pharmacologica Sinica. 2005 Jun;26(6):649-58. doi: 10.1111/j.1745-7254.2005.00119.x

One of the major obstacles in the development of bispecific antibodies (BsAb) has been the difficulty of producing the materials in sufficient quality and quantity by traditional technologies, such as the hybrid hybridoma and chemical conjugation methods. In contrast to the rapid and significant progress in the development of recombinant BsAb fragments (such as diabody and tandem single chain Fv), the successful design and production of full length IgG-like BsAb has been limited. Compared to smaller fragments, IgG-like BsAb have long serum half-life and are capable of supporting secondary immune functions, such as antibody-dependent cellular cytotoxicity and complement-mediated cytotoxicity. The development of IgG-like BsAb as therapeutic agents will depend heavily on our research progress in the design of recombinant BsAb constructs (or formats) and production efficiency. This review will focus on recent advances in various recombinant approaches to the engineering and production of IgG-like BsAb.

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06/01/05 | Tracking multiple mouse contours (without too many samples).
Branson K, Belongie S
Computer Vision and Pattern Recognition. 06/2005:1039-46

We present a particle filtering algorithm for robustly tracking the contours of multiple deformable objects through severe occlusions. Our algorithm combines a multiple blob tracker with a contour tracker in a manner that keeps the required number of samples small. This is a natural combination because both algorithms have complementary strengths. The multiple blob tracker uses a natural multi-target model and searches a smaller and simpler space. On the other hand, contour tracking gives more fine-tuned results and relies on cues that are available during severe occlusions. Our choice of combination of these two algorithms accentuates the advantages of each. We demonstrate good performance on challenging video of three identical mice that contains multiple instances of severe occlusion.

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Pavlopoulos Lab
05/31/05 | Establishing genetic transformation for comparative developmental studies in the crustacean Parhyale hawaiensis.
Pavlopoulos A, Averof M
Proceedings of the National Academy of Sciences of the United States of America. 2005 May 31;102(22):7888-93. doi: 10.1073/pnas.0501101102

The amphipod crustacean Parhyale hawaiensis has been put forward as an attractive organism for evolutionary developmental comparisons, and considerable effort is being invested in isolating developmental genes and studying their expression patterns in this species. The scope of these studies could be significantly expanded by establishing means for genetic manipulation that would enable direct studies of gene functions to be carried out in this species. Here, we report the use of the Minos transposable element for the genetic transformation of P. hawaiensis. Transformed amphipods can be obtained from approximately 30% of surviving individuals injected with both a Minos element carrying the 3xP3-DsRed fluorescent marker and with mRNA encoding the Minos transposase. Integral copies of the transposon are inserted into the host genome and are stably inherited through successive generations. We have used reporter constructs to identify a muscle-specific regulatory element from Parhyale, demonstrating that this transformation vector can be used to test the activity of cis-regulatory elements in this species. The relatively high efficiency of this transgenic methodology opens new opportunities for the direct study of cis-regulatory elements and gene functions in Parhyale, allowing functional studies to be carried out beyond previously established model systems in insects.

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05/01/05 | Antipsychotic drugs elevate mRNA levels of presynaptic proteins in the frontal cortex of the rat.
MacDonald ML, Eaton ME, Dudman JT, Konradi C
Biological Psychiatry. 2005 May 1;57(9):1041-51. doi: 10.3389/fnana.2010.00147

Molecular adaptations are believed to contribute to the mechanism of action of antipsychotic drugs (APDs). We attempted to establish common gene regulation patterns induced by chronic treatment with APDs.

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04/15/05 | Template-dependent morphogenesis of oriented calcite crystals in the presence of magnesium ions.
Han Y, Wysocki LM, Thanawala MS, Siegrist T, Aizenberg J
Angewandte Chemie (International ed. in English). 2005 Apr 15;44(16):2386-90. doi: 10.1002/anie.200462296
04/01/05 | Ataxin-3 suppresses polyglutamine neurodegeneration in Drosophila by a ubiquitin-associated mechanism.
Warrick JM, Morabito LM, Bilen J, Gordesky-Gold B, Faust LZ, Paulson HL, Bonini NM
Molecular Cell. 2005 Apr 1;18(1):37-48. doi: 10.1016/j.molcel.2005.02.030

Two central issues in polyglutamine-induced neurodegeneration are the influence of the normal function of the disease protein and modulation by protein quality control pathways. By using Drosophila, we now directly link host protein function and disease pathogenesis to ubiquitin pathways in the polyglutamine disease spinocerebellar ataxia type 3 (SCA3). Normal human ataxin-3–a polyubiquitin binding protein with ubiquitin protease activity–is a striking suppressor of polyglutamine neurodegeneration in vivo. This suppressor activity requires ubiquitin-associated activities of the protein and is dependent upon proteasome function. Our results highlight the critical importance of host protein function in SCA3 disease and a potential therapeutic role of ataxin-3 activity for polyglutamine disorders.

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04/01/05 | Genetic mapping of aphicarus -- a sex-linked locus controlling a wing polymorphism in the pea aphid (Acyrthosiphon pisum).
Braendle C, Caillaud MC, Stern DL
Heredity (Edinb). 2005 Apr;94(4):435-42. doi: 10.1038/sj.hdy.6800633

We have initiated research to determine the genetic basis of a male wing polymorphism in the pea aphid Acyrthosiphon pisum (Hemiptera: Aphididae). Previous studies showed that this polymorphism is controlled by a single biallelic locus, which we name aphicarus (api), on the X chromosome. Our objectives were to confirm that api segregates as a polymorphism of a single gene on the X chromosome, and to obtain molecular markers flanking api that can be used as a starting point for high-resolution genetic and physical mapping of the target region, which will ultimately allow the cloning of api. We have established an F2 population segregating for api and have generated X-linked AFLP markers. The segregation pattern of api in the F2 population shows that the male wing polymorphism segregates as a polymorphism of a single gene, or set of closely linked genes on the X chromosome. Using a subset of 78 F2 males, we have constructed a linkage map of the chromosomal region encompassing api using seven AFLP markers. The map spans 74.1 cM and we have mapped api to an interval of 10 cM. In addition, we confirmed X linkage of our AFLP markers and api by using one X-linked marker developed in an earlier study. Our study presents the first mapping of a gene with known function in aphids, and the results indicate that target gene mapping in aphids is feasible.

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Tjian Lab
04/01/05 | Maintenance of spermatogenesis requires TAF4b, a gonad-specific subunit of TFIID.
Falender AE, Freiman RN, Geles KG, Lo KC, Hwang K, Lamb DJ, Morris PL, Tjian R, Richards JS
Genes & Development. 2005 Apr 1;19(7):794-803. doi: 10.1073/pnas.1100640108

The establishment and maintenance of spermatogenesis in mammals requires specialized networks of gene expression programs in the testis. The gonad-specific TAF4b component of TFIID (formerly TAF(II)105) is a transcriptional regulator enriched in the mouse testis. Herein we show that TAF4b is required for maintenance of spermatogenesis in the mouse. While young Taf4b-null males are initially fertile, Taf4b-null males become infertile by 3 mo of age and eventually exhibit seminiferous tubules devoid of germ cells. At birth, testes of Taf4b-null males appear histologically normal; however, at post-natal day 3 gonocyte proliferation is impaired and expression of spermatogonial stem cell markers c-Ret, Plzf, and Stra8 is reduced. Together, these data indicate that TAF4b is required for the precise expression of gene products essential for germ cell proliferation and suggest that TAF4b may be required for the regulation of spermatogonial stem cell specification and proliferation that is obligatory for normal spermatogenic maintenance in the adult.

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