170 research outputs found

    Contrast estimation for parametric stationary determinantal point processes

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    We study minimum contrast estimation for parametric stationary determi-nantal point processes. These processes form a useful class of models for repulsive (or regular, or inhibitive) point patterns and are already applied in numerous statistical applications. Our main focus is on minimum contrast methods based on the Ripley's K-function or on the pair correlation function. Strong consistency and asymptotic normality of theses procedures are proved under general conditions that only concern the existence of the process and its regularity with respect to the parameters. A key ingredient of the proofs is the recently established Brillinger mixing property of stationary determinantal point processes. This work may be viewed as a complement to the study of Y. Guan and M. Sherman who establish the same kind of asymptotic properties for a large class of Cox processes, which in turn are models for clustering (or aggregation)

    Aspects of astrocyte energy metabolism, amino acid neurotransmitter homoeostasis and metabolic compartmentation

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    Astrocytes are key players in brain function; they are intimately involved in neuronal signalling processes and their metabolism is tightly coupled to that of neurons. In the present review, we will be concerned with a discussion of aspects of astrocyte metabolism, including energy-generating pathways and amino acid homoeostasis. A discussion of the impact that uptake of neurotransmitter glutamate may have on these pathways is included along with a section on metabolic compartmentation

    Impairment of the Organization of Locomotor and Exploratory Behaviors in Bile Duct-Ligated Rats

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    Hepatic encephalopathy (HE) arises from acute or chronic liver diseases and leads to several problems, including motor impairment. Animal models of chronic liver disease have extensively investigated the mechanisms of this disease. Impairment of locomotor activity has been described in different rat models. However, these studies are controversial and the majority has primarily analyzed activity parameters. Therefore, the aim of the present study was to evaluate locomotor and exploratory behavior in bile duct-ligated (BDL) rats to explore the spatial and temporal structure of behavior. Adult female Wistar rats underwent common bile duct ligation (BDL rats) or the manipulation of common bile duct without ligation (control rats). Six weeks after surgery, control and BDL rats underwent open-field, plus-maze and foot-fault behavioral tasks. The BDL rats developed chronic liver failure and exhibited a decrease in total distance traveled, increased total immobility time, smaller number of rearings, longer periods in the home base area and decreased percentage of time in the center zone of the arena, when compared to the control rats. Moreover, the performance of the BDL rats was not different from the control rats for the elevated plus-maze and foot-fault tasks. Therefore, the BDL rats demonstrated disturbed spontaneous locomotor and exploratory activities as a consequence of altered spatio-temporal organization of behavior

    Phosphorylation of Glutamine Synthetase on Threonine 301 Contributes to Its Inactivation During Epilepsy

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    The astrocyte-specific enzyme glutamine synthetase (GS), which catalyzes the amidation of glutamate to glutamine, plays an essential role in supporting neurotransmission and in limiting NH4+ toxicity. Accordingly, deficits in GS activity contribute to epilepsy and neurodegeneration. Despite its central role in brain physiology, the mechanisms that regulate GS activity are poorly defined. Here, we demonstrate that GS is directly phosphorylated on threonine residue 301 (T301) within the enzyme’s active site by cAMP-dependent protein kinase (PKA). Phosphorylation of T301 leads to a dramatic decrease in glutamine synthesis. Enhanced T301 phosphorylation was evident in a mouse model of epilepsy, which may contribute to the decreased GS activity seen during this trauma. Thus, our results highlight a novel molecular mechanism that determines GS activity under both normal and pathological conditions.</p

    Release of Juniperus thurifera woodlands from herbivore-mediated arrested succession in Spain

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    Question: Do abiotic constraints maintain monospecific woodlands of Juniperus thurifera? What is the role of biotic (livestock) versus abiotic (climate) drivers in the recruitment and growth of the different tree species? Location: Cabrejas range, Soria, north-central Spain, 1200m altitude. Methods: Stand history was reconstructed using dendroecology and spatial pattern analysis, combined with historical data of livestock abundances and climatic records. Results: J. thurifera establishment occurred in two distinct pulses, with a tree component establishing in the late 1800s to early 1900s. Quercus ilex and Pinus sylvestris establishment was evident only from the late 1970s onward. Recruitment events were related to reductions in livestock browsing. J. thurifera spatial structure was clumped and Q. ilex showed a short-scale aggregation to J. thurifera trees and saplings. Radial growth trends of J. thurifera saplings, Q. ilex and P. sylvestris were negatively related to livestock density. Summer drought limited the radial growth of all the study species, and P. sylvestris and Q. ilex grew faster than J. thurifera even after considering an age effect. Conclusions: The differences in radial growth patterns and recruitment pulses between species indicate that livestock browsing and not abiotic factors is the main factor controlling plant succession and structural development. In this process, J. thurifera acts as a nurse plant, facilitating the establishment of other tree species. Under the current low pressure from herbivores, formerly pure J. thurifera woodlands will change towards dense stands of mixed species composition

    Circadian Modulation of Gene Expression, but not Glutamate Uptake, in Mouse and Rat Cortical Astrocytes

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    Circadian clocks control daily rhythms including sleep-wake, hormone secretion, and metabolism. These clocks are based on intracellular transcription-translation feedback loops that sustain daily oscillations of gene expression in many cell types. Mammalian astrocytes display circadian rhythms in the expression of the clock genes Period1 (Per1) and Period2 (Per2). However, a functional role for circadian oscillations in astrocytes is unknown. Because uptake of extrasynaptic glutamate depends on the presence of Per2 in astrocytes, we asked whether glutamate uptake by glia is circadian.We measured glutamate uptake, transcript and protein levels of the astrocyte-specific glutamate transporter, Glast, and the expression of Per1 and Per2 from cultured cortical astrocytes and from explants of somatosensory cortex. We found that glutamate uptake and Glast mRNA and protein expression were significantly reduced in Clock/Clock, Per2- or NPAS2-deficient glia. Uptake was augmented when the medium was supplemented with dibutyryl-cAMP or B27. Critically, glutamate uptake was not circadian in cortical astrocytes cultured from rats or mice or in cortical slices from mice.We conclude that glutamate uptake levels are modulated by CLOCK, PER2, NPAS2, and the composition of the culture medium, and that uptake does not show circadian variations

    Ratiometric high-resolution imaging of JC-1 fluorescence reveals the subcellular heterogeneity of astrocytic mitochondria

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    Using the mitochondrial potential (ΔΨm) marker JC-1 (5,5′,6,6′-tetrachloro-1,1′,3,3′-tetraethylbenzimidazolylcarbocyanine iodide) and high-resolution imaging, we functionally analyzed mitochondria in cultured rat hippocampal astrocytes. Ratiometric detection of JC-1 fluorescence identified mitochondria with high and low ΔΨm. Mitochondrial density was highest in the perinuclear region, whereas ΔΨm tended to be higher in peripheral mitochondria. Spontaneous ΔΨm fluctuations, representing episodes of increased energization, appeared in individual mitochondria or synchronized in mitochondrial clusters. They continued upon withdrawal of extracellular Ca2+, but were antagonized by dantrolene or 2-aminoethoxydiphenylborate (2-APB). Fluo-3 imaging revealed local cytosolic Ca2+ transients with similar kinetics that also were depressed by dantrolene and 2-APB. Massive cellular Ca2+ load or metabolic impairment abolished ΔΨm fluctuations, occasionally evoking heterogeneous mitochondrial depolarizations. The detected diversity and ΔΨm heterogeneity of mitochondria confirms that even in less structurally polarized cells, such as astrocytes, specialized mitochondrial subpopulations coexist. We conclude that ΔΨm fluctuations are an indication of mitochondrial viability and are triggered by local Ca2+ release from the endoplasmic reticulum. This spatially confined organelle crosstalk contributes to the functional heterogeneity of mitochondria and may serve to adapt the metabolism of glial cells to the activity and metabolic demand of complex neuronal networks. The established ratiometric JC-1 imaging—especially combined with two-photon microscopy—enables quantitative functional analyses of individual mitochondria as well as the comparison of mitochondrial heterogeneity in different preparations and/or treatment conditions
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