Microglia and astrocytes play essential roles in the central nervous system contributing to many functions including homeostasis, immune response, blood-brain barrier maintenance and synaptic ...support. Evidence has emerged from experimental models of glial communication that microglia and astrocytes influence and coordinate each other and their effects on the brain environment. However, due to the difference in glial cells between humans and rodents, it is essential to confirm the relevance of these findings in human brains. Here, we aim to review the current knowledge on microglia-astrocyte crosstalk in humans, exploring novel methodological techniques used in health and disease conditions. This will include an in-depth look at cell culture and iPSCs,
studies, imaging and fluid biomarkers, genetics and transcriptomic data. In this review, we will discuss the advantages and limitations of these methods, highlighting the understanding these methods have brought the field on these cells communicative abilities, and the knowledge gaps that remain.
SNO+ will search for neutrinoless double beta decay by loading 780 tonnes of linear alkylbenzene liquid scintillator with O(tonne) of neodymium. Using natural Nd at 0.1% loading will provide 43.7 kg ...of 150Nd given its 5.6% abundance and allow the experiment to reach a sensitivity to the effective neutrino mass of 100-200 meV at 90% C.L in a 3 year run. The SNO+ detector has ultra low backgrounds with 7000 tonnes of water shielding and self-shielding of the scintillator. Distillation and several other purification techniques will be used with the aim of achieving Borexino levels of backgrounds. The experiment is fully funded and data taking with light-water will commence in 2012 with scintillator data following in 2013.
A review of accelerator long-baseline neutrino oscillation experiments is provided, including all experiments performed to date and the projected sensitivity of those currently in progress. ...Accelerator experiments have played a crucial role in the confirmation of the neutrino oscillation phenomenon and in precision measurements of the parameters. With a fixed baseline and detectors providing good energy resolution, precise measurements of the ratio of distance/energy (L/E) on the scale of individual events have been made and the expected oscillatory pattern resolved. Evidence for electron neutrino appearance has recently been obtained, opening a door for determining the CP violating phase as well as resolving the mass hierarchy and the octant of θ23; some of the last unknown parameters of the standard model extended to include neutrino mass.
Neuroinflammation is involved in the aetiology of many neurodegenerative disorders including Alzheimer's disease, Parkinson's disease and motor neuron disease. Whether neuroinflammation also plays an ...important role in the pathophysiology of frontotemporal dementia is less well known. Frontotemporal dementia is a heterogeneous classification that covers many subtypes, with the main pathology known as frontotemporal lobar degeneration. The disease can be categorized with respect to the identity of the protein that causes the frontotemporal lobar degeneration in the brain. The most common subgroup describes diseases caused by frontotemporal lobar degeneration associated with tau aggregation, also known as primary tauopathies. Evidence suggests that neuroinflammation may play a role in primary tauopathies with genome-wide association studies finding enrichment of genetic variants associated with specific inflammation-related gene loci. These loci are related to both the innate immune system, including brain resident microglia, and the adaptive immune system through possible peripheral T-cell involvement. This review discusses the genetic evidence and relates it to findings in animal models expressing pathogenic tau as well as to post-mortem and PET studies in human disease. Across experimental paradigms, there seems to be a consensus regarding the involvement of innate immunity in primary tauopathies, with increased microglia and astrocyte density and/or activation, as well as increases in pro-inflammatory markers. Whilst it is less clear as to whether inflammation precedes tau aggregation or vice versa; there is strong evidence to support a microglial contribution to the propagation of hyperphosphorylated in tau frontotemporal lobar degeneration associated with tau aggregation. Experimental evidence-albeit limited-also corroborates genetic data pointing to the involvement of cellular adaptive immunity in primary tauopathies. However, it is still unclear whether brain recruitment of peripheral immune cells is an aberrant result of pathological changes or a physiological aspect of the neuroinflammatory response to the tau pathology.
Abstract
In 1956 Reines & Cowan discovered the neutrino using a liquid scintillator detector. The neutrinos interacted with the scintillator, producing light that propagated across transparent ...volumes to surrounding photo-sensors. This approach has remained one of the most widespread and successful neutrino detection technologies used since. This article introduces a concept that breaks with the conventional paradigm of transparency by confining and collecting light near its creation point with an opaque scintillator and a dense array of optical fibres. This technique, called LiquidO, can provide high-resolution imaging to enable efficient identification of individual particles event-by-event. A natural affinity for adding dopants at high concentrations is provided by the use of an opaque medium. With these and other capabilities, the potential of our detector concept to unlock opportunities in neutrino physics is presented here, alongside the results of the first experimental validation.
Frontotemporal lobar degeneration with tau (FTLD-tau) is a group of tauopathies that underlie ∼50% of FTLD cases. Identification of genetic risk variants related to innate/adaptive immunity have ...highlighted a role for neuroinflammation and neuroimmune interactions in FTLD. Studies have shown microglial and astrocyte activation together with T cell infiltration in the brain of THY-Tau22 tauopathy mice. However, this remains to be confirmed in FTLD-tau patients. We conducted a detailed post-mortem study of FTLD-tau cases including 45 progressive supranuclear palsy with clinical frontotemporal dementia, 33 Pick's disease, 12 FTLD-MAPT and 52 control brains to characterize the link between phosphorylated tau (pTau) epitopes and the innate and adaptive immunity. Tau pathology was assessed in the cerebral cortex using antibodies directed against: Tau-2 (phosphorylated and unphosphorylated tau), AT8 (pSer202/pThr205), AT100 (pThr212/pSer214), CP13 (pSer202), PHF1 (pSer396/pSer404), pThr181 and pSer356. The immunophenotypes of microglia and astrocytes were assessed with phenotypic markers (Iba1, CD68, HLA-DR, CD64, CD32a, CD16 for microglia and GFAP, EAAT2, glutamine synthetase and ALDH1L1 for astrocytes). The adaptive immune response was explored via CD4+ and CD8+ T cell quantification and the neuroinflammatory environment was investigated via the expression of 30 inflammatory-related proteins using V-Plex Meso Scale Discovery. As expected, all pTau markers were increased in FTLD-tau cases compared to controls. pSer356 expression was greatest in FTLD-MAPT cases versus controls (P < 0.0001), whereas the expression of other markers was highest in Pick's disease. Progressive supranuclear palsy with frontotemporal dementia consistently had a lower pTau protein load compared to Pick's disease across tau epitopes. The only microglial marker increased in FTLD-tau was CD16 (P = 0.0292) and specifically in FTLD-MAPT cases (P = 0.0150). However, several associations were detected between pTau epitopes and microglia, supporting an interplay between them. GFAP expression was increased in FTLD-tau (P = 0.0345) with the highest expression in Pick's disease (P = 0.0019), while ALDH1L1 was unchanged. Markers of astrocyte glutamate cycling function were reduced in FTLD-tau (P = 0.0075; Pick's disease: P < 0.0400) implying astrocyte reactivity associated with a decreased glutamate cycling activity, which was further associated with pTau expression. Of the inflammatory proteins assessed in the brain, five chemokines were upregulated in Pick's disease cases (P < 0.0400), consistent with the recruitment of CD4+ (P = 0.0109) and CD8+ (P = 0.0014) T cells. Of note, the CD8+ T cell infiltration was associated with pTau epitopes and microglial and astrocytic markers. Our results highlight that FTLD-tau is associated with astrocyte reactivity, remarkably little activation of microglia, but involvement of adaptive immunity in the form of chemokine-driven recruitment of T lymphocytes.
An important aspect of cognition is whether animals live exclusively in the present or can anticipate the future. Defined as self-control, the ability to choose a large, remote reinforcer over a ...small, proximate reinforcer available at the same frequency has been examined in a number of species, often proving difficult to demonstrate. We investigated self-control for food in domestic fowl using a standard two-key operant task and an equivalent two-choice return maze (TCRM) task. When hens chose between a 2-s delay to a 3-s feed access (impulsive) and a 6-s delay to a 7-s feed access (self-control), they appeared unable to discriminate in the TCRM but were impulsive in the operant task. We explored reasons for not choosing self-control in the operant task, first by examining the relation between feed access time and actual feed intake. A second operant experiment examined whether failure to show self-control could be attributed to an inability to combine the delay and access (quantity) reward information associated with choices to reach overall predictions of value. New hens chose between a 2-s delay to a 3-s feed access (impulsive) and either a 22-s delay to a 22-s feed access (standard self-control) or a 6-s delay to a 22-s feed access (jackpot self-control). While hens were impulsive in the standard condition, they showed significant and pronounced self-control in the jackpot condition, eliminating the possibility of an absolute cognitive constraint. Impulsive behaviour can instead be explained by temporal discounting: perceived depreciation of reward value as a function of the uncertainty associated with delay. Implications for welfare are discussed.
A lucid dream is defined as occurring when an individual becomes aware that they are dreaming, and, while remaining asleep, can control some of the events or content of the dream. Frequent lucid ...dreamers have previously been shown to be more internal on Rotter’s Locus of Control (LOC) scale than are non-lucid dreamers. The present study found that frequent lucid dreamers (
n=22) had higher scores than non-lucid dreamers (
n=20) on the Internal dimension of Levenson’s LOC scale, but not on Levenson’s LOC Powerful Others and Chance dimensions. Frequent, and also occasional lucid dreamers (
n=15), also scored significantly higher on Need for Cognition and on Gough’s self-assessed Creative Personality scale, than did non-lucid dreamers. The results indicate a continuity between styles of waking and dreaming cognition, just as previous work has shown a continuity of content.
We report the final measurement of the neutrino oscillation parameters Δm322 and sin2 θ23 using all data from the MINOS and MINOS+ experiments. These data were collected using a total exposure of ...23.76 × 1020 protons on target producing νμ and νμ beams and 60.75 kt yr exposure to atmospheric neutrinos. The measurement of the disappearance of νμ and the appearance of νe events between the Near and Far detectors yields ... and ... at 68% C.L. for normal (inverted) hierarchy. (ProQuest: ... denotes formulae omited.).
SNO+ will search for neutrinoless double beta decay by loading 780 tonnes of linear alkylbenzene liquid scintillator with O(tonne) of neodymium. Using natural Nd at 0.1% loading will provide 43.7 kg ...of super(150)Nd given its 5.6% abundance and allow the experiment to reach a sensitivity to the effective neutrino mass of 100-200 meV at 90% C.L in a 3 year run. The SNO+ detector has ultra low backgrounds with 7000 tonnes of water shielding and self-shielding of the scintillator. Distillation and several other purification techniques will be used with the aim of achieving Borexino levels of backgrounds. The experiment is fully funded and data taking with light-water will commence in 2012 with scintillator data following in 2013.
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