Context-dependent Manner (context-dependent + manner)

Distribution by Scientific Domains


Selected Abstracts


The pallial basal ganglia pathway modulates the behaviorally driven gene expression of the motor pathway

EUROPEAN JOURNAL OF NEUROSCIENCE, Issue 7 2007
Lubica Kubikova
Abstract The discrete neural network for songbird vocal communication provides an effective system to study neural mechanisms of learned motor behaviors in vertebrates. This system consists of two pathways , a vocal motor pathway used to produce learned vocalizations and a vocal pallial basal ganglia loop used to learn and modify the vocalizations. However, it is not clear how the loop exerts control over the motor pathway. To study the mechanism, we used expression of the neural activity-induced gene ZENK (or egr-1), which shows singing-regulated expression in a social context-dependent manner: high levels in both pathways when singing undirected and low levels in the lateral part of the loop and in the robust nucleus of the arcopallium (RA) of the motor pathway when singing directed to another animal. Here, we show that there are two parallel interactive parts within the pallial basal ganglia loop, lateral and medial, which modulate singing-driven ZENK expression of the motor pathway nuclei RA and HVC, respectively. Within the loop, the striatal and pallial nuclei appear to have opposing roles; the striatal vocal nucleus lateral AreaX is required for high ZENK expression in its downstream nuclei, particularly during undirected singing, while the pallial vocal lateral magnocellular nucleus of the anterior nidopallium is required for lower expression, particularly during directed singing. These results suggest a dynamic molecular interaction between the basal ganglia pathway and the motor pathway during production of a learned motor behavior. [source]


COMPENSATING FOR OUR LOAD OF MUTATIONS: FREEZING THE MELTDOWN OF SMALL POPULATIONS

EVOLUTION, Issue 5 2000
Art Poon
Abstract We have investigated the reduction of fitness caused by the fixation of new deleterious mutations in small populations within the framework of Fisher's geometrical model of adaptation. In Fisher's model, a population evolves in an n -dimensional character space with an adaptive optimum at the origin. The model allows us to investigate compensatory mutations, which restore fitness losses incurred by other mutations, in a context-dependent manner. We have conducted a moment analysis of the model, supplemented by the numerical results of computer simulations. The mean reduction of fitness (i.e., expected load) scaled to one is approximately n/(n + 2Ne), where Ne is the effective population size. The reciprocal relationship between the load and Ne implies that the fixation of deleterious mutations is unlikely to cause extinction when there is a broad scope for compensatory mutations, except in very small populations. Furthermore, the dependence of load on n implies that pleiotropy plays a large role in determining the extinction risk of small populations. Differences and similarities between our results and those of a previous study on the effects of Ne and n are explored. That the predictions of this model are qualitatively different from studies ignoring compensatory mutations implies that we must be cautious in predicting the evolutionary fate of small populations and that additional data on the nature of mutations is of critical importance. [source]


Alterations in intranuclear localization of Runx2 affect biological activity,,

JOURNAL OF CELLULAR PHYSIOLOGY, Issue 3 2006
Sayyed K. Zaidi
The transcription factor Runx2 controls osteoblast proliferation and differentiation. Runx2 organizes and assembles gene-regulatory complexes in nuclear microenvironments where target genes are activated or suppressed in a context-dependent manner. Intranuclear localization of Runx2 is mediated by the nuclear matrix-targeting signal (NMTS), an autonomous motif with a loop (L1)-turn-loop (L2) structure that forms predicted protein,protein interaction surfaces. Here we examined the functional consequences of introducing mutations in the L1 and L2 loops of the NMTS. These mutant proteins enter the nucleus, interact with the hetero-dimeric partner Cbf,, and bind to DNA in vitro and in vivo. In addition, these mutants retain interaction with the carboxy-terminus interacting co-regulatory proteins that include TLE, YAP, and Smads. However, two critical mutations in the L2 domain of the NMTS decrease association of Runx2 with the nuclear matrix. These subnuclear targeting defective (STD) mutants of Runx2 compromise target gene activation or repression. The biological significance of these findings is reflected by decreased osteogenic differentiation of mesenchymal progenitors, concomitant with major changes in gene expression profiles, upon expression of the STD Runx2 mutant. Our results demonstrate that fidelity of temporal and spatial localization of Runx2 within the nucleus is functionally linked with biological activity. J. Cell. Physiol. 209: 935,942, 2006. © 2006 Wiley-Liss, Inc. [source]


Aminoglycoside-mediated partial suppression of MECP2 nonsense mutations responsible for Rett syndrome in vitro

JOURNAL OF NEUROSCIENCE RESEARCH, Issue 11 2010
Andreea C. Popescu
Abstract Rett syndrome is a pediatric neurological condition that affects primarily girls. Approximately 30% of Rett syndrome cases arise from point mutations that introduce a premature stop codon into the MECP2 gene. Several studies have now shown that certain aminoglycosides can facilitate read-through of some types of nonsense mutations in a context-dependent manner and allow the generation of a full-length protein. It remains mostly unclear whether different nonsense mutations of MECP2 will be responsive to aminoglycoside treatment. In this study, we tested whether the common premature terminating mutations of MECP2 seen in Rett syndrome cases can be partially suppressed by aminoglycoside administration. Our results show that aminoglycosides allow different mutant forms of MECP2 to be overcome in transiently transfected HEK293 cells, but with differing levels of efficiency. In addition, we also show that aminoglycosides increased the prevalence of full-length MeCP2 protein in a dose-dependent manner in a lymphocyte cell line derived from a Rett syndrome girl with the R255X mutation. This study helps to establish the "proof of principle" that some nonsense mutations causing Rett syndrome can be at least partially suppressed by drug treatment. © 2010 Wiley-Liss, Inc. [source]