DynamoSort: Using machine learning approaches for the automatic classification of seizure dynamotypes.

Objective: Epilepsy is characterised by unprovoked and recurring seizures, which can be electrically measured using electroencephalograms (EEG). To better understand the underlying mechanisms of seizures, researchers are exploring their temporal dynamics through the lens of dynamical systems modelling. Seizure initiation and termination patterns of spiking amplitude and frequency can be sorted into "dynamotypes", which may be able to serve as biomarkers for intervention.

The MRGPRX2-substance P pathway regulates mast cell migration.

Mast cells (MCs) are tissue-resident immune cells known to degranulate in response to FcεRI crosslinking or MRGPRX2 engagement. MCs are found close to nerves, but the mechanisms that regulate this privileged localization remain unclear. Here, we investigated MRGPRX2 expression patterns and specific activities in MCs.

Intracerebral delivery of antiseizure medications by microinvasive neural implants.

Focal epilepsy is a difficult disease to treat as two-thirds of patients will not respond to oral anti-seizure medications (ASMs) or have severe off-target effects that lead to drug discontinuation. Current non-pharmaceutical treatment methods (resection or ablation) are underutilized due to the associated morbidities, invasive nature and inaccessibility of seizure foci. Less invasive non-ablative modalities may potentially offer an alternative.

Discovery and Profiling of New Multimodal Phenylglycinamide Derivatives as Potent Antiseizure and Antinociceptive Drug Candidates.

We developed a focused series of original phenyl-glycinamide derivatives which showed potent activity across mouse seizure models, namely, maximal electroshock (MES) and 6 Hz (using both 32 and 44 mA current intensities) seizure models. Following intraperitoneal (.) administration, compound , which was identified as a lead molecule, demonstrated potent protection against all seizure models with ED values of 73.

P2X7 Receptor-Induced Human Mast Cell Degranulation Is Enhanced by Interleukin 33.

MCs are tissue-resident immune cells that strategically reside in barrier organs and respond effectively to a wide range of stimuli, such as IL-33, a mediator released upon epithelial damage. Adenosine triphosphate (ATP) accumulates at sites of tissue injury and is known to modulate MC activities. This study investigated how an inflammatory tissue environment rich in IL-33 modulates the ATP-mediated activation of MCs.

Utilizing Molecular Epidemiology and Citizen Science for the Surveillance of Lagoviruses in Australia.

Australia has multiple lagoviruses with differing pathogenicity. The circulation of these viruses was traditionally determined through opportunistic sampling events. In the lead up to the nationwide release of RHDVa-K5 (GI.

Spatial and temporal patterns of sarcoptic mange in wombats using the citizen science tool, WomSAT.

There is currently limited information regarding the levels of infection and distribution of sarcoptic mange in the wombat population throughout Australia. We analyzed cases of sarcoptic mange in bare-nosed wombats reported into WomSAT, a website and mobile phone application where citizen scientists can upload sightings of wombats, burrows, and sarcoptic mange status. We used Maxent software to predict locations and the environmental factors associated with sarcoptic mange occurrence in bare-nosed wombats.

Human Mast Cells Upregulate Cathepsin B, a Novel Marker of Itch in Psoriasis.

Mast cells (MCs) contribute to skin inflammation. In psoriasis, the activation of cutaneous neuroimmune networks commonly leads to itch. To dissect the unique contribution of MCs to the cutaneous neuroinflammatory response in psoriasis, we examined their density, distribution, relation to nerve fibres and disease severity, and molecular signature by comparing RNA-seq analysis of MCs isolated from the skin of psoriasis patients and healthy volunteers.

Glutamate dynamics in the dorsolateral striatum of rats with goal-directed and habitual cocaine-seeking behavior.

The shift from drug abuse to addiction is considered to arise from the transition between goal-directed and habitual control over drug behavior. Habitual responding for appetitive and skill-based behaviors is mediated by potentiated glutamate signaling in the dorsolateral striatum (DLS), but the state of the DLS glutamate system in the context of habitual drug-behavior remains undefined. Evidence from the nucleus accumbens of cocaine-experienced rats suggests that decreased transporter-mediated glutamate clearance and enhanced synaptic glutamate release contribute to the potentiated glutamate signaling that underlies the enduring vulnerability to relapse.

Mast cell tissue heterogeneity and specificity of immune cell recruitment.

Mast cells occupy a unique niche within tissues as long lived perpetrators of IgE mediated hypersensitivity and anaphylaxis, as well as other immune responses. However, mast cells are not identical in different tissues and the impact of this tissue heterogeneity on the interaction with other immune cells and on defined immune responses is still unclear. In this review, we synthesize the characteristics of mast cell heterogeneity in the gut and the skin.

Ascorbic Acid Reduces Neurotransmission, Synaptic Plasticity, and Spontaneous Hippocampal Rhythms in In Vitro Slices.

Ascorbic acid (AA; a.k.a.

Effects of methamphetamine-induced neurotoxicity on striatal long-term potentiation.

Rationale: Methamphetamine (METH) exposure is associated with damage to central monoamine systems, particularly dopamine signaling. Rodent models of such damage have revealed a decrease in the amplitude of phasic dopamine signals and significant striatal dysfunction, including changes in the molecular, system, and behavioral functions of the striatum. Dopamine signaling through D1 receptors promotes corticostriatal long-term potentiation (LTP), a critical substrate of these striatal functions.

Distribution and Genetic Diversity of Hepatitis E Virus in Wild and Domestic Rabbits in Australia.

In 2020, Hepatitis E virus (HEV) was detected for the first time in Australian rabbits. To improve our understanding of the genetic diversity and distribution of the virus, 1635 rabbit liver samples from locations across Australia were screened via RT-qPCR for HEV. HEV genomes were amplified and sequenced from 48 positive samples.

Spontaneous recurrent seizures in an intra-amygdala kainate microinjection model of temporal lobe epilepsy are differentially sensitive to antiseizure drugs.

The discovery and development of novel antiseizure drugs (ASDs) that are effective in controlling pharmacoresistant spontaneous recurrent seizures (SRSs) continues to represent a significant unmet clinical need. The Epilepsy Therapy Screening Program (ETSP) has undertaken efforts to address this need by adopting animal models that represent the salient features of human pharmacoresistant epilepsy and employing these models for preclinical testing of investigational ASDs. One such model that has garnered increased interest in recent years is the mouse variant of the Intra-Amygdala Kainate (IAK) microinjection model of mesial temporal lobe epilepsy (MTLE).

Screening of prototype antiseizure and anti-inflammatory compounds in the Theiler's murine encephalomyelitis virus model of epilepsy.

Objective: Infection with Theiler's murine encephalomyelitis virus (TMEV) in C57Bl/6J mice results in handling-induced seizures and is useful for evaluating compounds effective against infection-induced seizures. However, to date only a few compounds have been evaluated in this model, and a comprehensive study of antiseizure medications (ASMs) has not yet been performed. Furthermore, as the TMEV infection produces marked neuroinflammation, an evaluation of prototype anti-inflammatory compounds is needed as well.

Development of an antiseizure drug screening platform for Dravet syndrome at the NINDS contract site for the Epilepsy Therapy Screening Program.

Objective: Dravet syndrome (DS) is a rare but catastrophic genetic epilepsy, with 80% of patients carrying a mutation in the SCN1A gene. Currently, no antiseizure drug (ASD) exists that adequately controls seizures. In the clinic, individuals with DS often present first with a febrile seizure and, subsequently, generalized tonic-clonic seizures that can continue throughout life.

Interleukin-33 Amplifies Human Mast Cell Activities Induced by Complement Anaphylatoxins.

Both, aberrant mast cell responses and complement activation contribute to allergic diseases. Since mast cells are highly responsive to C3a and C5a, while Interleukin-33 (IL-33) is a potent mast cell activator, we hypothesized that IL-33 critically regulates mast cell responses to complement anaphylatoxins. We sought to understand whether C3a and C5a differentially activate primary human mast cells, and probe whether IL-33 regulates C3a/C5a-induced mast cell activities.

Evaluation of subchronic administration of antiseizure drugs in spontaneously seizing rats.

Objective: Approximately 30% of patients with epilepsy do not experience full seizure control on their antiseizure drug (ASD) regimen. Historically, screening for novel ASDs has relied on evaluating efficacy following a single administration of a test compound in either acute electrical or chemical seizure induction. However, the use of animal models of spontaneous seizures and repeated administration of test compounds may better differentiate novel compounds.

Discovery of the First Vitamin K Analogue as a Potential Treatment of Pharmacoresistant Seizures.

Despite the availability of more than 25 antiseizure drugs on the market, approximately 30% of patients with epilepsy still suffer from seizures. Thus, the epilepsy therapy market has a great need for a breakthrough drug that will aid pharmacoresistant patients. In our previous study, we discovered a vitamin K analogue, , which displayed modest antiseizure activity in zebrafish and mouse seizure models.

The current approach of the Epilepsy Therapy Screening Program contract site for identifying improved therapies for the treatment of pharmacoresistant seizures in epilepsy.

The Epilepsy Therapy Screening Program (ETSP), formerly known as the Anticonvulsant Screening Program (ASP), has played an important role in the preclinical evaluation of many of the antiseizure drugs (ASDs) that have been approved by the FDA and thus made available for the treatment of seizures. Recent changes to the animal models used at the contract site of the ETSP at the University of Utah have been implemented in an attempt to better model the unmet clinical needs of people with pharmacoresistant epilepsy and thus identify improved therapies. In this review, we describe the changes that have occurred over the last several years in the screening approach used at the contract site and, in particular, detail the pharmacology associated with several of the animal models and assays that are either new to the program or have been recently characterized in more depth.

The relationship between reported domestic canine parvovirus cases and wild canid distribution.

Canine parvovirus (CPV) is an important and often fatal pathogen of domestic dogs. It is resistant in the environment and cross-species transmission has been indicated in some canid populations, but never in Australia. The aim of this study was to determine if an association exists between 1.