83 research outputs found

    Suppression of Signal Transducer and Activator of Transcription 3–Dependent B Lymphocyte Terminal Differentiation by Bcl-6

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    Lymphocytes usually differentiate into effector cells within days after antigen exposure, except in germinal centers where terminal differentiation is delayed while somatic hypermutation creates high-affinity antibody mutants. Here we investigate whether arrest of terminal differentiation can be mediated by BCL-6, a transcriptional repressor that is expressed by germinal center B cells and is required for this phase of B cell development. We find that BCL-6 suppresses the differentiation of transformed and primary B cells to plasma cells by inhibiting the signal transducer and activator of transcription 3–dependent expression of the major regulator of plasma cell development, the B lymphocyte–induced maturation protein (Blimp-1). This function of BCL-6 as a repressor of B lymphocyte differentiation may also underlie the association between chromosomal translocations of its gene and B cell lymphomas

    Early alterations in the MCH system link aberrant neuronal activity and sleep disturbances in a mouse model of Alzheimer’s disease

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    Early Alzheimer’s disease (AD) is associated with hippocampal hyperactivity and decreased sleep quality. Here we show that homeostatic mechanisms transiently counteract the increased excitatory drive to CA1 neurons in App NL-G-F mice, but that this mechanism fails in older mice. Spatial transcriptomics analysis identifies Pmch as part of the adaptive response in App NL-G-F mice. Pmch encodes melanin-concentrating hormone (MCH), which is produced in sleep–active lateral hypothalamic neurons that project to CA1 and modulate memory. We show that MCH downregulates synaptic transmission, modulates firing rate homeostasis in hippocampal neurons and reverses the increased excitatory drive to CA1 neurons in App NL-G-F mice. App NL-G-F mice spend less time in rapid eye movement (REM) sleep. App NL-G-F mice and individuals with AD show progressive changes in morphology of CA1-projecting MCH axons. Our findings identify the MCH system as vulnerable in early AD and suggest that impaired MCH-system function contributes to aberrant excitatory drive and sleep defects, which can compromise hippocampus-dependent functions

    Reconstructed Dynamics of Rapid Extinctions of Chaparral-Requiring Birds in Urban Habitat Islands

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    The distribution of native, chaparral-requiring bird species was determined for 37 isolated fragments of canyon habitat ranging in size from 0.4 to 104 hectares in coastal, urban San Diego County, California The area of chaparral habitat and canyon age (time since isolation of the habitat fragment) explains most of the variation in the number of chaparral-requiring bird species. In addition, the distribution of native predators may influence species number. There is statistical evidence that coyotes control the populations of smaller predators such as foxes and domestic cats. The absence of coyotes may lead to higher levels of predation by a process of mesopredator release. The distance of canyons from other patches of chaparral habitat does not add significantly to the explained variance in chaparral-requiring species number–probably because of the virtual inability of most chaparral-requiring species to disperse through developed areas and nonscrub habitats. These results and other lines of evidence suggest that chaparral-requiring birds in isolated canyons have very high rates of extinction, in part because of their low vagility. The best predictors of vulnerability of the individual species are their abundances (densities) in undisturbed habitat and their body sizes; together these two variables account for 95 percent of the variation in canyon occupancy. A hypothesis is proposed to account for the similarity between the steep slopes of species-area curves for chaparral-requiring birds and the slopes for some forest birds on small islands or in habitat fragments. The provision of corridors appears to be the most effective design and planning feature for preventing the elimination of chaparral-requiring species in a fragmented landscape.Peer Reviewedhttp://deepblue.lib.umich.edu/bitstream/2027.42/74761/1/j.1523-1739.1988.tb00337.x.pd

    Effective Long-Distance Pollen Dispersal in Centaurea jacea

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    BACKGROUND: Agri-environment schemes play an increasingly important role for the conservation of rare plants in intensively managed agricultural landscapes. However, little is known about their effects on gene flow via pollen dispersal between populations of these species. METHODOLOGY/PRINCIPAL FINDINGS: In a 2-year experiment, we observed effective pollen dispersal from source populations of Centaurea jacea in restored meadows, the most widespread Swiss agri-environment scheme, to potted plants in adjacent intensively managed meadows without other individuals of this species. Potted plants were put in replicated source populations at 25, 50, 100 m and where possible 200 m distance from these source populations. Pollen transfer among isolated plants was prevented by temporary bagging, such that only one isolated plant was accessible for flower visitors at any one time. Because C. jacea is self-incompatible, seed set in single-plant isolates indicated insect mediated effective pollen dispersal from the source population. Seed set was higher in source populations (35.7+/-4.4) than in isolates (4.8+/-1.0). Seed set declined from 18.9% of that in source populations at a distance of 25 m to 7.4% at 200 m. At a distance of 200 m seed set was still significantly higher in selfed plants, indicating long-distance effective pollen dispersal up to 200 m. Analyses of covariance suggested that bees contributed more than flies to this long-distance pollen dispersal. We found evidence that pollen dispersal to single-plant isolates was positively affected by the diversity and flower abundance of neighboring plant species in the intensively managed meadow. Furthermore, the decline of the dispersal was less steep when the source population of C. jacea was large. CONCLUSIONS: We conclude that insect pollinators can effectively transfer pollen from source populations of C. jacea over at least 200 m, even when "recipient populations" consisted of single-plant isolates, suggesting that gene flow by pollen over this distance is very likely. Source population size and flowering environment surrounding recipient plants appear to be important factors affecting pollen dispersal in C. jacea. It is conceivable that most insect-pollinated plants in a network of restored sites within intensively managed grassland can form metapopulations, if distances between sites are of similar magnitude as tested here

    Sleep regulation: modeling and EEG analysis

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    Oscillatory patterns in the electroencephalogram at sleep onset

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    Falling asleep is a gradually unfolding process. We investigated the role of various oscillatory activities including sleep spindles and alpha and delta oscillations at sleep onset (SO) by automatically detecting oscillatory events. We used two datasets of healthy young males, eight with four baseline recordings, and eight with a baseline and recovery sleep after 40 h of sustained wakefulness. We analyzed the 2-min interval before SO (stage 2) and the five consecutive 2-min intervals after SO. The incidence of delta/theta events reached its maximum in the first 2-min episode after SO, while the frequency of them was continuously decreasing from stage 1 onwards, continuing over SO and further into deeper sleep. Interestingly, this decrease of the frequencies of the oscillations were not affected by increased sleep pressure, in contrast to the incidence which increased. We observed an increasing number of alpha events after SO, predominantly frontally, with their prevalence varying strongly across individuals. Sleep spindles started to occur after SO, with first an increasing then a decreasing incidence and a continuous decrease in their frequency. Again, the frequency of the spindles was not altered after sleep deprivation. Oscillatory events revealed derivation dependent aspects. However, these regional aspects were not specific of the process of SO but rather reflect a general sleep related phenomenon. No individual traits of SO features (incidence and frequency of oscillations) and their dynamics were observed. Delta/theta events are important features for the analysis of SO in addition to slow waves.ISSN:1550-9109ISSN:0161-810
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