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Combination Therapy as Enhanced Antidote to Poisoning

Certain pesticides can be harmful, and there is a need for effective antidotes that can reverse accidental over-exposure by farm workers. UC San Diego researchers have recently developed a therapeutic modality that is a combination of compositions that may be effective as an antidote.

Preventing the Buildup of Potentially Toxic Protein Aggregates Through Manipulation of Fused in Sarcoma RNA Binding Protein (FUS)

The FUS gene encodes a multifunctional protein component of the heterogeneous nuclear ribonucleoprotein (hnRNP) complex. The hnRNP complex is involved in pre-mRNA splicing and the export of fully processed mRNA to the cytoplasm. This protein belongs to the FET family of RNA-binding proteins (FUS, EWSR1 and TAF15, constitute the FET protein family) which have been implicated in cellular processes that include regulation of gene expression, maintenance of genomic integrity and mRNA/microRNA processing. Alternative splicing results in multiple transcript variants. Defects in this gene result in amyotrophic lateral sclerosis type 6. Stress granules are transient protein-RNA complexes that are formed and dismantled inside the cytosol as a result of external stress or injury to neurons. Several genes whose mutation causes amyotrophic lateral sclerosis (ALS) and multisystem proteinopathies are RNA binding proteins. Currently, there are no known techniques that have demonstrated reducing or removing these genes will increase the lifespan of disease neurons that model ALS.

Manipulation of Ataxin 2 Gene (ATXN2) to Treat Amyotrophic Lateral Sclerosis (ALS)

Stress granules are transient protein-RNA complexes that are formed and dismantled inside the cytosol as a result of external stress or injury to neurons. Several genes whose mutation causes amyotrophic lateral sclerosis (ALS) and multisystem proteinopathies are RNA binding proteins. Currently, there are no known techniques that have demonstrated reducing or removing these genes will increase the lifespan of disease neurons that model ALS.   The Ataxin 2 gene belongs to a group of genes associated with microsatellite-expansion diseases, a class of neurological and neuromuscular disorders caused by expansion of short stretches of repetitive DNA, that include amyotrophic lateral sclerosis, spinocerebellar ataxia-2, and may be associated with susceptibility to type I diabetes, obesity and hypertension.

Development of Methods to Inhibit IL-1β and IL-18 Production

Macrophages respond to pathogens and tissue damage via pattern recognition receptors (PRR) that sense pathogen (PAMP) or damage (DAMP) associated molecular patterns. NLRP3, a member of the Nod-like receptor (NLR) family that is induced upon macrophage activation, senses cytosolic oxidized mitochondrial DNA (ox-mtDNA) that is generated when activated macrophages are exposed to NLRP3- activating DAMPs, such as ATP, uric acid, or amyloid β, triggers IL-1β and IL-18 production and release. IL-1β and IL-18 are members of the IL-1 family of cytokines representing two of eleven members. As a whole, the IL-1 group of cytokines can induce strong inflammatory signals. Moreover, IL-1β and IL-18 are unique members because they are inactive until undergoing proteasomal cleavage by caspase-1 leading to the formation of active biological forms. Recent work has shown that NLRP3 inflammasome dependent production of IL-1β and IL-18 is involved in the pathogenesis of many devastating diseases, including cancer, Alzheimer’s disease, rheumatoid diseases and cryopyrin-associated periodic syndromes. and autoimmune diseases such as lupus or Still’s diseases. Thus, there exists a need to modulate the production of both IL-1β and IL-18.

Automated Selection of Myocardial Inversion Time with a Convolutional Neural Network

Magnetic resonance imaging (MRI) has been noted for its excellent soft tissue imaging capability with zero radiation dose. It has repeatedly been touted as the imaging modality of the future, but due to its complexity, long exam times and high cost, its growth has been severely limited. This especially has been the case for cardiac MRI, which only accounts for about I percent of all MRI exams in the United States. Delayed enhancement (DE) imaging is an essential component of cardiac MRI, widely used for the evaluation of myocardial scar and viability. The selection of an optimal inversion time (TI), known as the myocardial null point (TINP), to suppress the background myocardial signal is required to optimize image contrast in myocardial delayed enhancement (MDE) acquisitions. Incorrect selection of TINP can impair diagnostic quality. In certain diffuse myocardial diseases such as amyloidosis, it may be difficult to identify a single optimal null point. Further, it is known that TINP varies after intravenous contrast administration, and is therefore time-sensitive. In practice, selection of myocardial inversion time is generally performed through visual inspection and selection of TINP from an inversion recovery scout acquisition. This is dependent on the skill of a technologist or physician to select the optimal inversion time, which may not be readily available outside of specialized centers. However, such methods still rely on visual inspection of an image series by a trained human observer to select an optimal myocardial inversion time. A way to overcome these deficiencies is to embrace Deep learning approaches, including convolutional neural networks (CNNs),     which have the potential to automate selection of inversion time, and are the current state-of-the-art technology for image classification, segmentation, localization, and Spatial Temporal Ensemble Myocardium Inversion NETwork (STEMI-NET) prediction. However, these static CNN models have some drawbacks which could be overcome via the use of dynamic temporal activities for object recognition.

Easy to Wear Dry EEG Sensors for Human–Computer Interactions

Measurements based on electroencephalogram (EEG) are made by placing electrodes over a human scalp to apply and receive electrical signals. Various implementations of EEG sensors are available. The electroencephalogram (EEG) has recently gained popularity for use in various non-clinical studies but still lacks any robust, single application outside well-controlled laboratory environments. As the limitations of EEG are mostly due to the low spatial resolution, using multiple bio-sensing modalities proves to be better performing than EEG alone

Microfluidic Device: Optics-Free, Non-Contact Measurements of Fluids, Bubbles, and Particles in Microchannels

Microfluidic devices have long been touted as a powerful analytical tool with which to characterize a wide range of analytes, including particles, and cells. Despite the apparent convenience of microfluidic technologies for applications in healthcare, such devices often rely on capital-intensive optics and other peripheral equipment that limit throughput, perhaps because the majority of microfluidic devices operate using optics-based principles, which typically require high-speed or sensitive cameras, sophisticated confocal microscopes, vibration isolation tables, and laser excitation systems.

Methods of Discovering New Bile Acids and Use in Treating Inflammatory Diseases

A mosaic of cross-phyla chemical interactions occurs between all metazoans and their microbiomes. In humans, the gut harbors the heaviest microbial load, but many organs, particularly those with a mucosal surface, associate with highly adapted and evolved microbial consortia. The microbial residents within these organ systems are increasingly well characterized, yielding a good understanding of human microbiome composition. However, we have yet to elucidate the full chemical impact the microbiome exerts on an animal and the breadth of the chemical diversity it contributes. A number of molecular families are known to be shaped by the microbiome including short-chain fatty acids, indoles, aromatic amino acid metabolites, complex polysaccharides, and host sphingolipids and bile acids. These metabolites profoundly affect host physiology and are being explored for their roles in both health and disease. The synthesis of bile acids takes place in the liver and recent research has shown that bile acids can act as signaling molecules and activate a number of molecules. A primary focus has been on the Farnesoid X receptor (FXR) which plays an important role in bile acid synthesis and in regulation of glucose, lipid and energy metabolism.