4,030 research outputs found
The thalamic reticular nucleus: a functional hub for thalamocortical network dysfunction in schizophrenia and a target for drug discovery
The thalamus (comprising many distinct nuclei) plays a key role in facilitating sensory discrimination and cognitive processes through connections with the cortex. Impaired thalamocortical processing has long been considered to be involved in schizophrenia. In this review we focus on the thalamic reticular nucleus (TRN) providing evidence for it being an important communication hub between the thalamus and cortex and how it may play a key role in the pathophysiology of schizophrenia. We first highlight the functional neuroanatomy, neurotransmitter localisation and physiology of the TRN. We then present evidence of the physiological roles of the TRN in relation to oscillatory activity, cognition and behaviour. Next we discuss the role of the TRN in rodent models of risk factors for schizophrenia (genetic and pharmacological) and provide evidence for TRN deficits in schizophrenia. Finally we discuss new drug targets for schizophrenia in relation to restoring TRN circuitry dysfunction
Cancer immunology and canine malignant melanoma: a comparative review
Oral canine malignant melanoma (CMM) is a spontaneously occurring aggressive tumour with relatively few medical treatment options, which provides a suitable model for the disease in humans. Historically, multiple immunotherapeutic strategies aimed at provoking both innate and adaptive anti-tumour immune responses have been published with varying levels of activity against CMM. Recently, a plasmid DNA vaccine expressing human tyrosinase has been licensed for the adjunct treatment of oral CMM. This article reviews the immunological similarities between CMM and the human counterpart; mechanisms by which tumours evade the immune system; reasons why melanoma is an attractive target for immunotherapy; the premise of whole cell, dendritic cell (DC), viral and DNA vaccination strategies alongside preliminary clinical results in dogs. Current “gold standard” treatments for advanced human malignant melanoma are evolving quickly with remarkable results being achieved following the introduction of immune checkpoint blockade and adoptively transferred cell therapies. The rapidly expanding field of cancer immunology and immunotherapeutics means that rational targeting of this disease in both species should enhance treatment outcomes in veterinary and human clinics
Magnetically operated check valve
A magnetically operated check valve is disclosed. The valve is comprised of a valve body and a movable poppet disposed therein. A magnet attracts the poppet to hold the valve shut until the force of fluid flow through the valve overcomes the magnetic attraction and moves the poppet to an unseated, open position. The poppet and magnet are configured and disposed to trap a magnetically attracted particulate and prevent it from flowing to a valve seating region
Effect of male circumcision on risk of sexually transmitted infections and cervical cancer in women.
The Warty Dory, Allocyttus verrucosus, New to the Fish Fauna of Canada
In April 2010, a Warty Dory, Allocyttus verrucosus (Gilchrist, 1906), was captured during commercial fishing activities in the Labrador Sea. This is the first record for Canada and the northwest Atlantic Ocean
BDNF and JNK-signalling modulate cortical interneuron and perineuronal net development: implications for schizophrenia-linked 16p11.2 duplication syndrome
Schizophrenia is a neurodevelopmental disorder caused by the interaction of genetic and environmental risk factors. One of the strongest genetic risk variants is duplication of chr.16p11.2. Schizophrenia is characterised by cortical GABAergic interneuron dysfunction, and disruption to surrounding extracellular matrix structures, perineuronal nets (PNNs). Developmental maturation of GABAergic interneurons, and also the resulting closure of the critical period of cortical plasticity, is regulated by brain derived neurotrophic factor (BDNF), although the mechanisms involved are unknown. Here, we show that BDNF promotes GABAergic interneuron and PNN maturation through JNK signalling. In mice reproducing the 16p11.2 duplication, where the JNK upstream activator Taok2 is overexpressed, we find that JNK is overactive and there are developmental abnormalities in PNNs which persist into adulthood. Prefrontal cortex parvalbumin expression is reduced while PNN intensity is increased. Additionally, we report a unique role for TAOK2 signalling in the regulation of parvalbumin interneurons. Our work implicates TAOK2-JNK signalling in cortical interneuron and PNN development, and in the responses to BDNF. It also demonstrates that over-activation of this pathway in conditions associated with schizophrenia risk causes long-lasting disruption in cortical interneurons
Economic Feasibility of Ethanol Production from Sweet Sorghum Juice in Texas
The economic feasibility of producing ethanol from sweet sorghum juice is projected using Monte Carlo simulation models to estimate the price ethanol plants will likely have to pay for sweet sorghum and the uncertain returns for ethanol plants. Ethanol plants in high yielding regions will likely generate returns on assets of 11%-12% and in low yield areas the returns on assets will be less than 10%.Sweet Sorghum, Ethanol, Monte Carlo Simulation, Agribusiness, Agricultural Finance, Crop Production/Industries, Farm Management, Risk and Uncertainty, D20 G10 D81 C15,
Localisation of gamma-ray interaction points in thick monolithic CeBr3 and LaBr3:Ce scintillators
Localisation of gamma-ray interaction points in monolithic scintillator
crystals can simplify the design and improve the performance of a future
Compton telescope for gamma-ray astronomy. In this paper we compare the
position resolution of three monolithic scintillators: a 28x28x20 mm3 (length x
breadth x thickness) LaBr3:Ce crystal, a 25x25x20 mm3 CeBr3 crystal and a
25x25x10 mm3 CeBr3 crystal. Each crystal was encapsulated and coupled to an
array of 4x4 silicon photomultipliers through an optical window. The
measurements were conducted using 81 keV and 356 keV gamma-rays from a
collimated 133Ba source. The 3D position reconstruction of interaction points
was performed using artificial neural networks trained with experimental data.
Although the position resolution was significantly better for the thinner
crystal, the 20 mm thick CeBr3 crystal showed an acceptable resolution of about
5.4 mm FWHM for the x and y coordinates, and 7.8 mm FWHM for the z-coordinate
(crystal depth) at 356 keV. These values were obtained from the full position
scans of the crystal sides. The position resolution of the LaBr3:Ce crystal was
found to be considerably worse, presumably due to the highly diffusive optical
in- terface between the crystal and the optical window of the enclosure. The
energy resolution (FWHM) measured for 662 keV gamma-rays was 4.0% for LaBr3:Ce
and 5.5% for CeBr3. The same crystals equipped with a PMT (Hamamatsu R6322-100)
gave an energy resolution of 3.0% and 4.7%, respectively
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