Publications by authors named "Matthew Nolan"

Cannabis sativa L. (Cannabis) is a medicinal plant that produces and stores an abundance of therapeutic and psychoactive secondary metabolites, including phytocannabinoids and terpenes, in the glandular trichomes of its female flowers. We postulate that glandular trichome productivity has been under strong artificial selection in the pursuit for ever more potent cultivars.

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Cannabis sativa is a dioecious crop whose agricultural productivity is linked to its sex expression. In a medicinal context, only female flowers produce an abundance of glandular trichomes responsible for producing valuable cannabinoids. Thus, understanding sex-determining factors is vital in Cannabis sativa crop improvement for specific end uses.

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Cannabis ( L.) flower glandular trichomes (GTs) are the main site of cannabinoid synthesis. Phytohormones, such as jasmonic acid (JA) and salicylic acid (SA), have been shown to increase cannabinoid content in cannabis flowers, but how this is regulated remains unknown.

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Myelination facilitates the rapid conduction of action potentials along axons. In the central nervous system (CNS), myelinated axons vary over 100-fold in diameter, with conduction speed scaling linearly with increasing diameter. Axon diameter and myelination are closely interlinked, with axon diameter exerting a strong influence on myelination.

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Cannabis trichome development progresses in distinct phases that underpin the dynamic biosynthesis of cannabinoids and terpenes. This study investigates the molecular mechanisms underlying cannabinoid and terpenoid biosynthesis in glandular trichomes of Cannabis sativa (CsGTs) throughout their development. Female Cannabis sativa c.

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Brain-resident macrophages, microglia, have been proposed to have an active role in synaptic refinement and maturation, influencing plasticity and circuit-level connectivity. Here we show that several neurodevelopmental processes previously attributed to microglia can proceed without them. Using a genetically modified mouse that lacks microglia (Csf1r), we find that intrinsic properties, synapse number and synaptic maturation are largely normal in the hippocampal CA1 region and somatosensory cortex at stages where microglia have been implicated.

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Interactions between excitatory and inhibitory neurons are critical to computations in cortical circuits but their organization is difficult to assess with standard electrophysiological approaches. Within the medial entorhinal cortex, representation of location by grid and other spatial cells involves circuits in layer 2 in which excitatory stellate cells interact with each other via inhibitory parvalbumin expressing interneurons. Whether this connectivity is structured to support local circuit computations is unclear.

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Cannabis sativa L. glandular trichomes synthesize large amounts of secondary metabolites, predominantly cannabinoids and terpenoids. The associated demand for carbon and energy makes glandular trichomes strong sink tissues with indications that their secondary metabolism is coupled to the availability of photoassimilates.

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Grid firing fields have been proposed as a neural substrate for spatial localisation in general or for path integration in particular. To distinguish these possibilities, we investigate firing of grid and non-grid cells in the mouse medial entorhinal cortex during a location memory task. We find that grid firing can either be anchored to the task environment, or can encode distance travelled independently of the task reference frame.

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Betz cells, named in honor of Volodymyr Betz (1834-1894), who described them as "giant pyramids" in the primary motor cortex of primates and other mammalian species, are layer V extratelencephalic projection (ETP) neurons that directly innervate α-motoneurons of the brainstem and spinal cord. Despite their large volume and circumferential dendritic architecture, to date, no single molecular criterion has been established that unequivocally distinguishes adult Betz cells from other layer V ETP neurons. In primates, transcriptional signatures suggest the presence of at least two ETP neuron clusters that contain mature Betz cells; these are characterized by an abundance of axon guidance and oxidative phosphorylation transcripts.

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Objectives: Objective risk communication tools can supplement clinical judgement and support the understanding of potential health risks. This study used the Theoretical Domains Framework (TDF) to identify barriers and facilitators to implementing a risk communication aid within primary care dental consultations.

Methods: Dentists (N = 13), recruited via a dental practice database and through professional contacts were interviewed using a TDF-informed semi-structured interview schedule.

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Nuclear clearance and cytoplasmic accumulations of the RNA-binding protein TDP-43 are pathological hallmarks in almost all patients with amyotrophic lateral sclerosis (ALS) and up to 50% of patients with frontotemporal dementia (FTD) and Alzheimer's disease. In Alzheimer's disease, TDP-43 pathology is predominantly observed in the limbic system and correlates with cognitive decline and reduced hippocampal volume. Disruption of nuclear TDP-43 function leads to abnormal RNA splicing and incorporation of erroneous cryptic exons in numerous transcripts including Stathmin-2 (STMN2, also known as SCG10) and UNC13A, recently reported in tissues from patients with ALS and FTD.

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Although mutations in dozens of genes have been implicated in familial forms of amyotrophic lateral sclerosis (fALS) and frontotemporal degeneration (fFTD), most cases of these conditions are sporadic (sALS and sFTD), with no family history, and their etiology remains obscure. We tested the hypothesis that somatic mosaic mutations, present in some but not all cells, might contribute in these cases, by performing ultra-deep, targeted sequencing of 88 genes associated with neurodegenerative diseases in postmortem brain and spinal cord samples from 404 individuals with sALS or sFTD and 144 controls. Known pathogenic germline mutations were found in 20.

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Memory consolidation involves interactions between the hippocampus and other cortical areas. A new study identifies neurons in the medial entorhinal cortex that over learning increase their coordination with hippocampal replay events, suggesting a route for consolidation of spatial memories.

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Standard models for spatial and episodic memory suggest that the lateral entorhinal cortex (LEC) and medial entorhinal cortex (MEC) send parallel independent inputs to the hippocampus, each carrying different types of information. Here, we evaluate the possibility that information is integrated between divisions of the entorhinal cortex prior to reaching the hippocampus. We demonstrate that, in mice, fan cells in layer 2 (L2) of LEC that receive neocortical inputs, and that project to the hippocampal dentate gyrus, also send axon collaterals to layer 1 (L1) of the MEC.

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In fragile X syndrome (FX), the leading monogenic cause of autism, excessive neuronal protein synthesis is a core pathophysiology; however, an overall increase in protein expression is not observed. Here, we tested whether excessive protein synthesis drives a compensatory rise in protein degradation that is protective for FX mouse model (Fmr1) neurons. Surprisingly, although we find a significant increase in protein degradation through ubiquitin proteasome system (UPS), this contributes to pathological changes.

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Neurons in the retrohippocampal cortices play crucial roles in spatial memory. Many retrohippocampal neurons have firing fields that are selectively active at specific locations, with memory for rewarded locations associated with reorganization of these firing fields. Whether this is the sole strategy for representing spatial memories is unclear.

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Establishing the biological basis of cognition and its disorders will require high precision spatiotemporal measurements of neural activity. Recently developed genetically encoded voltage indicators (GEVIs) report both spiking and subthreshold activity of identified neurons. However, maximally capitalizing on the potential of GEVIs will require imaging at millisecond time scales, which remains challenging with standard camera systems.

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Cheap, easy-to-produce oral vaccines are needed for control of coccidiosis in chickens to reduce the impact of this disease on welfare and economic performance. yeast expressing three antigens were developed and delivered as heat-killed, freeze-dried whole yeast oral vaccines to chickens in four separate studies. After vaccination, replication was reduced following low dose challenge (250 oocysts) in Hy-Line Brown layer chickens (p<0.

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The deep layers of the entorhinal cortex are important for spatial cognition, as well as memory storage, consolidation and retrieval. A long-standing hypothesis is that deep-layer neurons relay spatial and memory-related signals between the hippocampus and telencephalon. We review the implications of recent circuit-level analyses that suggest more complex roles.

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is a common cause of coccidiosis in chickens, a disease that has a huge economic impact on poultry production. Knowledge of immunity to and the specific mechanisms that contribute to differing levels of resistance observed between chicken breeds and between congenic lines derived from a single breed of chickens is required. This study aimed to define differences in the kinetics of the immune response of two inbred lines of White Leghorn chickens that exhibit differential resistance (line C.

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Seizures can emerge from multiple or large foci in temporal lobe epilepsy, complicating focally targeted strategies such as surgical resection or the modulation of the activity of specific hippocampal neuronal populations through genetic or optogenetic techniques. Here, we evaluate a strategy in which optogenetic activation of medial septal GABAergic neurons, which provide extensive projections throughout the hippocampus, is used to control seizures. We utilized the chronic intrahippocampal kainate mouse model of temporal lobe epilepsy, which results in spontaneous seizures and as is often the case in human patients, presents with hippocampal sclerosis.

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More than 68 billion chickens were produced globally in 2018, emphasising their major contribution to the production of protein for human consumption and the importance of their pathogens. Protozoan Eimeria spp. are the most economically significant parasites of chickens, incurring global costs of more than UK £10.

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