22 research outputs found

    The Contexts and Role of Government Policies in the Development of Cultural Creativity in Safavid Iran

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    Creativity in its general sense is the condition for cultural dynamism and the development of civilization. One of the strengths of contemporary Western civilization is the attraction and employment of elites. Cultural creativity can lead to symbolic production that is especially manifest in works of art. The purpose of this article is to explain the path of cultural creativity in the Safavid historical period. Actually, in terms of historical and artistic works, the Safavid period stands unique in Iranian history, which is a proof of the development of cultural creativity at that time. This article examines the role of government in promoting cultural creativity with a policy approach. The main question is "what policies led to the growth and development of cultural creativity in the Safavid period?" To answer this question, the pre-Safavid cultural context underlying subsequent policies has been examined. Also, based on historical propositions, an attempt has been made to extract and categorize the cultural and public policies of the Safavid government that have directly and indirectly affected cultural creativity. The results of this research, which was conducted by the library method, have identified a set of policies and actions of the Safavid government that have been effective in promoting cultural creativity. Cultural policies are categorized into four categories: identity, religion, development, and advocacy. Also, the policy of cultural interaction and exposure to cultural diversity has been identified as an effective one in the field of production and consumption of cultural products and the growth of creativity. The combination of these cultural and other public policies in the Safavid period, which led to the improvement of economic conditions and the formation of new social classes, was the cause of the growth and development of cultural creativity

    Cell number in the inferior olive of nervous and leaner mutant mice

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    Naturally occurring cell death is an important feature of neuronal network development: the absence of adequate postsynaptic target neurons during a critical period may result in the death of presynaptic neurons, the degree of death varying inversely with the size of the target population. Studies of mouse mutants with abnormal cerebellar development provide support for this neuron/target relationship in circuits within the CNS. In the present study we analysed the inferior olivary cell population in two cerebellar mutant mice, nervous (nr/nr) and leaner (Cacnalala/la). In these mice Purkinje cell degeneration begins near the end of the first postnatal month. In nervous mice the loss starts at postnatal day 20 (P20) and by the end of second month almost 90% of the Purkinje cells in the hemisphere and 50% in the vermis have disappeared. In leaner mice Purkinje cell loss starts after P30 and by P60 almost 50% of these cells are lost. We report here a loss of one third of inferior olivary neurons in the nervous mutation while the entire population appears intact in the leaner mouse. These results allow better definition of the end of the period of target dependency of inferior olive neurons. Their implications for the cell-cell interactions in the developing olivo-cerebellar system are discussed

    Deletion of the GluR delta 2 Receptor in the Hotfoot Mouse Mutant Causes Granule Cell Loss, Delayed Purkinje Cell Death, and Reductions in Purkinje Cell Dendritic Tree Area

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    International audienceRecent studies have found that in the cerebellum, the delta 2 glutamate receptor (GluR delta 2) plays a key role in regulating the differentiation of parallel fiber-Purkinje synapses and mediating key physiological functions in the granule cell-Purkinje cell circuit. In the hotfoot mutant or GluR delta 2 knockout mice, the absence of GluR delta 2 expression results in impaired motor-related tasks, ataxia, and disruption of long-term depression at parallel fiber-Purkinje cell synapses. The goal of this study was to determine the long-term consequences of deletion of GluR delta 2 expression in the hotfoot mutant (GluR delta 2 (ho/ho) ) on Purkinje and granule cell survival and Purkinje cell dendritic differentiation. Quantitative estimates of Purkinje and granule cell numbers in 3-, 12-, and 20-month-old hotfoot mutants and wild-type controls showed that Purkinje cell numbers are within control values at 3 and 12 months in the hotfoot mutant but reduced by 20 % at 20 months compared with controls. In contrast, the number of granule cells is significantly reduced from 3 months onwards in GluR delta 2 (ho/ho) mutant mice compared to wild-type controls. Although the overall structure of Purkinje cell dendrites does not appear to be altered, there is a significant 27 % reduction in the cross-sectional area of Purkinje cell dendritic trees in the 20-month-old GluR delta 2 (ho/ho) mutants. The interpretation of the results is that the GluR delta 2 receptor plays an important role in the long-term organization of the granule-Purkinje cell circuit through its involvement in the regulation of parallel fiber-Purkinje cell synaptogenesis and in the normal functioning of this critical cerebellar circuit

    Neuronal cell loss in heterozygous staggerer mutant mice: A model for genetic contributions to the aging process

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    Staggerer is a neurological mutation of mice that causes a severe ataxia correlated with digenesis of the cerebellar cortex. The Purkinje cell population in the homozygous mutant is reduced in size with a near total atrophy of dendritic structure. Further, the cells are ectopic and are reduced in number by about 75%. All of these phenotypes have been shown to be direct effects of the staggerer gene on the Purkinje cell itself. As an indirect consequence of gene action, virtually all of the cerebellar granule cells die as do 60% of the cells of the inferior olive. The mutation is described as recessive because the heterozygote, +/sg, is behaviorally normal and the mature cerebellum shows none of the defects described in the homozygous mutant. We report here that, as the +/sg mouse advances in age, a syndrome of cell losses is observed. While these losses are not as severe as in the homozygote, by 12 months of age 35% of the Purkinje cells are gone, as are 35% of the granule cells and 40% of the cells in the inferior olive. We propose that these results illustrate a synergy between the aging process and the heterozygous genotype. Neither alone is sufficient to cause the cell loss. This interaction suggests that the +/sg represents a new model for the genetic contribution to regressive CNS changes during aging

    Changes in the Distribution of the \textbf \textitα 3 Na ^\textrm+ /K ^\textrm+ ATPase Subunit in Heterozygous Lurcher Purkinje Cells as a Genetic Model of Chronic Depolarization during Development

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    International audienceA common assumption of excitotoxic mechanisms in the nervous system is that the ionic imbalance resulting from overstimulation of glutamate receptors and increased Na+ and Ca++ influx overwhelms cellular energy metabolic systems leading to cell death. The goal of this study was to examine how a chronic Na+ channel leak current in developing Purkinje cells in the heterozygous Lurcher mutant (+/Lc) affects the expression and distribution of the α3 subunit of the Na+/K+ ATPase pump, a key component of the homeostasis system that maintains ionic equilibrium in neurons. The expression pattern of the catalytic α3 Na+/K+ ATPase subunit was analyzed by immunohistochemistry, histochemistry, and Western Blots in wild type (WT) and +/Lc cerebella at postnatal days P10, P15, and P25 to determine if there are changes in the distribution of active Na+/K+ ATPase subunits in degenerating Purkinje cells. The results suggest that the expression of the catalytic α3 subunit is altered in chronically depolarized +/Lc Purkinje cells, although the density of active Na+/K+ ATPase pumps is not significantly altered compared with WT in the cerebellar cortex at P15, and then declines from P15 to P25 in the +/Lc cerebellum as the +/Lc Purkinje cells degenerate

    Cerebral Purkinje cells provide target support over a limited spatial range: Evidence from lurcher chimeric mice

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    The distribution of Purkinje cells, granule cells, and olivary neurons was quantitatively analyzed in a lurcher +/Lc ⇆ C3H/HeJ chimera in which the surviving wild type Purkinje cells were unilaterally distributed in the left hemicerebella. The left hemisphere of this mouse contains 7600 Purkinje cells, approximately 10% of the number of Purkinje cells in inbred C3H/HeJ mice. The right hemisphere contains 300 Purkinje cells, all of which are found within 200 μm of the midline. As in other +/Lc ⇆ wild type chimeras, the ratio of granule cells to Purkinje cells is increased in the left hemisphere, reflecting increased granule cell survival. In the right hemisphere, however, the number of granule cells is reduced to that found in +/Lc mutants. In the inferior olive, almost twice as many neurons are found in the right nucleus as opposed to the left nucleus. As the projections of olivary neurons are crossed, the number of olivary neurons is increased in the nuclei that project to the cerebellar hemisphere containing Purkinje cells compared to the olivary nuclei that project to the cerebellar hemisphere with almost no Purkinje cells. The preferential survival of granule cells and olivary neurons that either occupy or project to the hemicerebellum containing Purkinje cells suggests that the availability of trophic support from target Purkinje cell neurons is spatially restricted

    Enhanced Survival of Wild-Type and Lurcher Purkinje Cells In Vitro Following Inhibition of Conventional PKCs or Stress-Activated MAP Kinase Pathways

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    International audienceRecent studies using both dissociated and organotypic cell cultures have shown that heterozygous Lurcher (Lc/+) Purkinje cells (PCs) grown in vitro share many of the same survival and morphological characteristics as Lc/+ PCs in vivo. We have used this established tissue culture system as a valuable model for studying cell death mechanisms in a relatively simple system where neurodegeneration is induced by a constitutive cation leak mediated by the Lurcher mutation in the delta 2 glutamate receptor (GluR delta 2). In this study, Ca++ imaging and immunocytochemistry studies indicate that intracellular levels of Ca++ are chronically increased in Lc/+ PCs and the concentration and/or distribution of the conventional PKC gamma isoform is altered in degenerating Lc/+ PCs. To begin to characterize the molecular mechanisms that regulate Lc/+ PC death, the contributions of conventional PKC pathways and of two MAP kinase family members, JNK and p38, were examined in slice cultures from wild-type and Lc/+ mutant mouse cerebellum. Cerebellar slice cultures from P0 pups were treated with either a conventional PKC inhibitor, a JNK inhibitor, or a p38 inhibitor either from 0 to 14 or 7 to 14 DIV. Treatment with either of the three inhibitors from 0 DIV significantly increased wild type and Lc/+ PC survival through 14 DIV, but only Lc/+ PC survival was significantly increased following treatments from 7 to 14 DIV. The results suggest that multiple PC death pathways are induced by the physical trauma of making organotypic slice cultures, naturally-occurring postnatal cell death, and the GluR delta 2 (Lc) mutation

    A Comparative Study on Visual Detection of <i>Mycobacterium tuberculosis</i> by Closed Tube Loop-Mediated Isothermal Amplification: Shedding Light on the Use of Eriochrome Black T

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    Loop-mediated isothermal amplification is a promising candidate for the rapid detection of Mycobacterium tuberculosis. However, the high potential for carry-over contamination is the main obstacle to its routine use. Here, a closed tube LAMP was intended for the visual detection of Mtb to compare turbidimetric and two more favorable colorimetric methods using calcein and hydroxy naphthol blue (HNB). Additionally, a less studied dye (i.e., eriochrome black T (EBT)) was optimized in detail in the reaction for the first time. Mtb purified DNA and 30 clinical specimens were used to respectively determine the analytical and diagnostic sensitivities of each method. The turbidimetric method resulted in the best analytical sensitivity (100 fg DNA/reaction), diagnostic sensitivity and specificity (100%), and time-to-positivity of the test (15 min). However, this method is highly prone to subjective error in reading the results. Moreover, HNB-, calcein-, and EBT-LAMP could respectively detect 100 fg, 1 pg, and 1 pg DNA/reaction (the analytical sensitivities) in 30, 15, and 30 min, while the diagnostic sensitivity and specificity were respectively 93.3% and 100% for them all. Interestingly, EBT-LAMP showed the lowest potential for subjective error in reading the results. This report helps judiciously choose the most appropriate visual method, taking a step forward toward the field applicability of LAMP for the detection of Mtb, particularly in resource-limited settings

    Developmental studies of the inferior olivary nucleus in staggerer mutant mice

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    The neurological mutation, staggerer, causes a severe disruption in the integrity of the olivo-cerebellar circuitry. The primary site of action is the Purkinje cell population which is reduced in cell number, with cells that are atrophic in dendritic structure, small in size and ectopic in position. This primary defect has a cascade effect on the Purkinje cell-afferent populations, leading to the target-related cell death of virtually all of the cerebellar granule cells and the majority of the neurons in the inferior olive. As part of our ongoing study of the cell-cell interactions in the cerebellar circuitry, we have studied the inferior olive of the staggerer mutant from birth to adulthood. We find that the reduction in olive neuron number does not occur until after birth in the mutants. On the day of birth, the number of cells is indistinguishable in mutants and in wild type. Similarly, we find that the four principal subnuclei of the olive are well defined at birth, but regress to a state of poor resolution during the first 3 postnatal weeks. Finally, Golgi impregnations reveal that of the two morphological classes of inferior olive neurons, only one class- the Type II or complex dendritic type survive in the mutant. These results are discussed in terms of their implications for the cell-cell interactions in the developing olivocerebellar circuit
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