Localization of NG2 immunoreactive neuroglia cells in the rat locus coeruleus and their plasticity in response to stress

The locus coeruleus (LC) nucleus modulates adaptive behavioural responses to stress and dysregulation of LC neuronal activity is implicated in stress-induced mental illnesses. The LC is composed primarily of noradrenergic neurons together with various glial populations. A neuroglia cell-type largely unexplored within the LC is the NG2 cell. NG2 cells serve primarily as oligodendrocyte precursor cells throughout the brain. However, some NG2 cells are in synaptic contact with neurons suggesting a role in information processing. The aim of this study was to neurochemically and anatomically characterise NG2 cells within the rat LC. Furthermore, since NG2 cells have been shown to proliferate in response to traumatic brain injury, we investigated whether such NG2 cells plasticity also occurs in response to emotive insults such as stress. Immunohistochemistry and confocal microscopy revealed that NG2 cells were enriched within the pontine region occupied by the LC. Close inspection revealed that a sub-population of NG2 cells were located within unique indentations of LC noradrenergic somata and were immunoreactive for the neuronal marker NeuN whilst NG2 cell processes formed close appositions with clusters immunoreactive for the inhibitory synaptic marker proteins gephyrin and the GABA-A receptor alpha3-subunit, on noradrenergic dendrites. In addition, LC NG2 cell processes were decorated with vesicular glutamate transporter 2 immunoreactive puncta. Finally, ten days of repeated restraint stress significantly increased the density of NG2 cells within the LC. The study demonstrates that NG2 IR cells are integral components of the LC cellular network and they exhibit plasticity as a result of emotive challenges

Pre-exposure embrittlement of sensitized alumimium-magnesium alloy, 5083-H116

Environment-sensitive fracture of aluminum-magnesium alloys containing above ~3 wt% magnesium historically has been considered under anodic-dissolution control. Information from more recent studies, however, suggests a hydrogen-related process is also often involved. Further evidence supporting the involvement of a hydrogen-related process of during Intergranular stress corrosion cracking (IGSCC) will be presented using information gleaned from smooth and pre-cracked test specimens, previously sensitized over a range of temperatures in both ‘dry’ and ‘wet’ conditions and then subjected to rising-load testing in a range of environments. A detailed evaluation of the IGSCC using X-ray computed tomography to provide 3-D images and ultra-high-resolution electron microscopy to characterize selected regions within intergranular stress corrosion cracks enables mechanistic insights

On the role of anaxonic local neurons in the crossover to continuously varying exponents for avalanche activity

Local anaxonic neurons with graded potential release are important ingredients of nervous systems, present in the olfactory bulb system of mammalians, in the human visual system, as well as in arthropods and nematodes. We develop a neuronal network model including both axonic and anaxonic neurons and monitor the activity tuned by the following parameters: The decay length of the graded potential in local neurons, the fraction of local neurons, the largest eigenvalue of the adjacency matrix and the range of connections of the local neurons. Tuning the fraction of local neurons, we derive the phase diagram including two transition lines: A critical line separating subcritical and supercritical regions, characterized by power law distributions of avalanche sizes and durations, and a bifurcation line. We find that the overall behavior of the system is controlled by a parameter tuning the relevance of local neuron transmission with respect to the axonal one. The statistical properties of spontaneous activity are affected by local neurons at large fractions and in the condition that the graded potential transmission dominates the axonal one. In this case the scaling properties of spontaneous activity exhibit continuously varying exponents, rather than the mean field branching model universality class

Spatiotemporal distribution of GABA_A receptor subunits within Layer II of mouse medial entorhinal cortex:implications for grid cell excitability

GABAergic parvalbumin-expressing (PV+) interneurons provide powerful inhibitory modulation of grid cells in layer II of the medial entorhinal cortex (MEC LII). However, the molecular machinery through which PV+ cells regulate grid cell activity is poorly defined. PV+ interneurons impart inhibitory modulation primarily via GABA-A receptors (GABAARs). GABAARs are pentameric ion channels assembled from a repertoire of 19 subunits. Multiple subunit combinations result in a variety of receptor subtypes mediating functionally diverse postsynaptic inhibitory currents. Whilst the broad expression patterns of GABAAR subunits within the EC have been reported, those expressed by individual MEC LII cell types, in particular grid cells candidates, stellate and pyramidal cells, are less well described. Stellate and pyramidal cells are distinguished by their selective expression of reelin (RE+) and calbindin (CB+) respectively. Thus, the overall aim of this study was to provide a high resolution analysis of the major (α and γ) GABAAR subunits expressed in proximity to somato-dendritic PV+ boutons, on RE+ and CB+ cells, using immunohistochemistry, confocal microscopy and quantitative RT-PCR (qPCR). Clusters immunoreactive for the α1 and γ2 subunits decorated the somatic membranes of both RE+ and CB+ cells and were predominantly located in apposition to clusters immunoreactive for PV and vesicular GABA transporter (VGAT), suggesting expression in GABAergic synapses innervated by PV interneurons. Although intense α2 subunit-immunopositive clusters were evident in hippocampal fields located in close proximity to the EC, no specific signal was detected in MEC LII RE+ and CB+ profiles. Immunoreactivity for the α3 subunit was detected in all RE+ somata. In contrast, only a sub-population of CB+ cells was α3 immunopositive. These included CB-α3 cells which were both PV+ and PV−. Furthermore, α3 subunit mRNA and immunofluorescence decreased significantly between P 15 and P 25, a period implicated in the functional maturation of grid cells. Finally, α5 subunit immunoreactivity was detectable only on CB+ cells, not on RE+ cells. The present data demonstrates that physiologically distinct GABAAR subtypes are selectively expressed by CB+ and RE+ cells. This suggests that PV+ interneurons could utilize distinct postsynaptic signaling mechanisms to regulate the excitability of these different, candidate grid cell sub-populations

Genetics and molecular mechanisms of resistance to powdery mildews in tomato (Solanum lycopersicum) and its wild relatives

Powdery mildews (PMs) cause disease in a wide range of plant species including important crops. Taking tomato as an example, here we review findings on the genetic basis and mechanisms of plant resistance to PMs. First, we present a summary of our research on tomato resistance to two PM species, with the focus on Oidium neolycopersici. We discuss the genetics of resistance to this pathogen in tomato. Then, we compare different forms of resistance mediated by different resistance genes based on molecular and cytological data. Also, we provide a comparison between these resistance genes in tomato with those in barley, Arabidopsis and wheat, in order to present a model for the genetic basis of resistance to PMs in plants. We try to accommodate these resistance mechanisms in the current model of plant innate immunity. At the end we discuss possibilities to translate these findings to practical approaches in breeding for resistance to PMs in crops

Phylogenetic relationships of Iranian Infectious Pancreatic Necrosis Virus (IPNV) based on deduced amino acid sequences of genome segment A and B cDNA

Infectious Pancreatic Necrosis Virus (IPNV) is the causal agent of a highly contagious disease that affects many species of fish and shellfish. This virus causes economically important diseases of farmed rainbow trout, Oncorhynchus mykiss, in Iran which is often associated with the transmission of pathogens from European resources. In this study, moribund rainbow trout fry were collected during an outbreak of IPNV in three different fish farms in one northern province (Mazandaran), and two west provinces (Chaharmahal and Bakhtiari, and Kohgiluyeh and Boyer Ahmad) of Iran. We investigated full genome sequence of Iranian IPNV and compared it with previously identified IPNV sequences. The sequences of different structural and non-structural protein genes were compared with other aquatic birnaviruses sequenced to date. Our results showed that the Iranian isolate fall within genogroup 5, serotype A2 strain SP, having 99 % identity with the strain 1146 from Spain. These results suggest that the Iranian isolate may have originated from Europe

Identification of intraneuronal amyloid beta oligomers in locus coeruleus neurons of Alzheimer's patients and their potential impact on inhibitory neurotransmitter receptors and neuronal excitability

The author's final peer reviewed version can be found by following the URI link. The Publisher's final version can be found by following the DOI link.Aims Amyloid β oligomers (AβO) are potent modulators of Alzheimer’s pathology, yet their impact on one of the earliest brain regions to exhibit signs of the condition, the locus coeruleus (LC), remains to be determined. Of particular importance is whether AβO impact the spontaneous excitability of LC neurons. This parameter determines brain‐wide noradrenaline (NA) release, and thus NA‐mediated brain functions, including cognition, emotion and immune function, which are all compromised in Alzheimer’s. Therefore, the aim of the study was to determine the expression profile of AβO in the LC of Alzheimer’s patients and to probe their potential impact on the molecular and functional correlates of LC excitability, using a mouse model of increased Aβ production (APP‐PSEN1). Methods and Results Immunohistochemistry and confocal microscopy, using AβO‐specific antibodies, confirmed LC AβO expression both intraneuronally and extracellularly in both Alzheimer’s and APP‐PSEN1 samples. Patch clamp electrophysiology recordings revealed that APP‐PSEN1 LC neuronal hyperexcitability accompanied this AβO expression profile, arising from a diminished inhibitory effect of GABA, due to impaired expression and function of the GABA‐A receptor (GABAAR) α3 subunit. This altered LC α3‐GABAAR expression profile overlapped with AβO expression in samples from both APP‐PSEN1 mice and Alzheimer’s patients. Finally, strychnine‐sensitive glycine receptors (GlyRs) remained resilient to Aβ‐induced changes and their activation reversed LC hyperexcitability. Conclusions The data suggest a close association between AβO and α3‐GABAARs in the LC of Alzheimer’s patients, and their potential to dysregulate LC activity, thereby contributing to the spectrum of pathology of the LC‐NA system in this condition

Temporal networks of face-to-face human interactions

The ever increasing adoption of mobile technologies and ubiquitous services allows to sense human behavior at unprecedented levels of details and scale. Wearable sensors are opening up a new window on human mobility and proximity at the finest resolution of face-to-face proximity. As a consequence, empirical data describing social and behavioral networks are acquiring a longitudinal dimension that brings forth new challenges for analysis and modeling. Here we review recent work on the representation and analysis of temporal networks of face-to-face human proximity, based on large-scale datasets collected in the context of the SocioPatterns collaboration. We show that the raw behavioral data can be studied at various levels of coarse-graining, which turn out to be complementary to one another, with each level exposing different features of the underlying system. We briefly review a generative model of temporal contact networks that reproduces some statistical observables. Then, we shift our focus from surface statistical features to dynamical processes on empirical temporal networks. We discuss how simple dynamical processes can be used as probes to expose important features of the interaction patterns, such as burstiness and causal constraints. We show that simulating dynamical processes on empirical temporal networks can unveil differences between datasets that would otherwise look statistically similar. Moreover, we argue that, due to the temporal heterogeneity of human dynamics, in order to investigate the temporal properties of spreading processes it may be necessary to abandon the notion of wall-clock time in favour of an intrinsic notion of time for each individual node, defined in terms of its activity level. We conclude highlighting several open research questions raised by the nature of the data at hand.Comment: Chapter of the book "Temporal Networks", Springer, 2013. Series: Understanding Complex Systems. Holme, Petter; Saram\"aki, Jari (Eds.

Syndapin-2 mediated transcytosis of amyloid-β across the blood–brain barrier

open access articleA deficient transport of amyloid-β across the blood–brain barrier, and its diminished clearance from the brain, contribute to neurodegenerative and vascular pathologies, such as Alzheimer’s disease and cerebral amyloid angiopathy, respectively. At the blood–brain barrier, amyloid-β efflux transport is associated with the low-density lipoprotein receptor-related protein 1. However, the precise mechanisms governing amyloid-β transport across the blood–brain barrier, in health and disease, remain to be fully understood. Recent evidence indicates that the low-density lipoprotein receptor-related protein 1 transcytosis occurs through a tubulation-mediated mechanism stabilized by syndapin-2. Here, we show that syndapin-2 is associated with amyloid-β clearance via low-density lipoprotein receptor-related protein 1 across the blood–brain barrier. We further demonstrate that risk factors for Alzheimer’s disease, amyloid-β expression and ageing, are associated with a decline in the native expression of syndapin-2 within the brain endothelium. Our data reveals that syndapin-2-mediated pathway, and its balance with the endosomal sorting, are important for amyloid-β clearance proposing a measure to evaluate Alzheimer’s disease and ageing, as well as a target for counteracting amyloid-β build-up. Moreover, we provide evidence for the impact of the avidity of amyloid-β assemblies in their trafficking across the brain endothelium and in low density lipoprotein receptor-related protein 1 expression levels, which may affect the overall clearance of amyloid-β across the blood–brain barrier

Local-feature-based similarity measure for stochastic resonance in visual perception of spatially structured images

For images, stochastic resonance or useful-noise effects have previously been assessed with low-level pixel-based information measures. Such measures are not sensitive to coherent spatial structures usually existing in images. As a result, we show that such measures are not sufficient to properly account for stochastic resonance occurring in visual perception. We introduce higher-level similarity measures, inspired from visual perception, and based on local feature descriptors of scale invariant feature transform (SIFT) type. We demonstrate that such SIFT-based measures allow for an assessment of stochastic resonance that matches the visual perception of images with spatial structures. Constructive action of noise is registered in this way with both additive noise and multiplicative speckle noise. Speckle noise, with its grainy appearance, is particularly prone to introducing spurious spatial structures in images, and the stochastic resonance visually perceived and quantitatively assessed with SIFT-based measures is specially examined in this context