Researchers from UC San Diego and Oregon Health Science Univeristy developed a microelectrode grid for continuous interoperative neuromonitoring. The microelectrode grid includes a flexible substrate with low impedance electrochemical interface materials on conducting metal pads. The metal pads are connectable to stimulation/acquisition electronics through metal lead interconnects forming stimulation and recording channels and eventually to bonding pads. A flap within the substrate is movable away from the remainder of the substrate while at least some of the metal pads on the remainder of the substrate can remain in contact with an organ when the flap is moved away from the remainder of the substrate.

Researchers at the University of California, Davis have developed a sleep quality measuring device to measure waking electroencephalogram (EEG) test to determine the adequacy of sleep

Researchers at the University of California, Davis have developed a technology to expedite COVID-19 diagnosis and treatment using viral spike protein (S-protein) targeted peptides Zika virus envelop protein.

The rippled sheet was proposed by Pauling and Corey as a structural class in 1953. Following approximately a half century of only minimal activity in the field, the experimental foundation began to emerge, with some of the key papers published over the course of the last decade. Researchers at UC Santa Cruz have explored the structure of and have discovered ways to form new beta rippled sheets. 

Researchers at UC Irvine have identified and tested the FDA approved thrombin inhibitor Dabigatran etexilate for treatment of pain related conditions, seizure conditions and exogenously induced chemical neurotoxicity. Dabigatran etexilate stabilizes function of neuronal Kv7 potassium channels which are low-voltage gated potassium channels that regulate neuronal firing. Kv7 channels generate reversible high frequency firing of neurons in response to various neurotransmitters and hormones. This transient hyperactivity sensitizes neurons so that they can facilitate responses to essential information. Dabigatran etexilate stabilizes the function of Kv7 channels. As it is already FDA approved, this treatment will be well tolerated.

Researchers from UC San Diego's Neuroelectronic Lab (https://neuroelectronics.ucsd.edu/) demonstrate that they can predict neural activity at deeper layers of the brain by only recording potentials from brain surface. This was achieved by performing multimodal experiments with an ultra-high density transparent graphene electrode technology and developing neural network methods to learn nonlinear dynamic between different modalities. They used cross modality inference to predict the activity at deep layers from surface. Prediction of neural activity at depth have the potential to open up new possibilities for developing minimally invasive neural prosthetics or targeted treatments for various neurological disorders.

Researchers from UC San Diego's Neuroelectronics Lab invented an implantable brain electrode technology which allows recording interactions between different cortex regions or interactions of cortex with other subcortical structures. The technology is called Neuro‐FITM. Flexibility and transparency of Neuro‐ FITM allow integration of electrophysiological recordings with any optical imaging (such as high resolution multiphoton imaging) or stimulation technology (such as optogenetics).

Researchers from UC San Diego have developed a patent-pending wearable device for concurrently assessing afferent and efferent visual functions. The invention details novel mobile brain-computer interfacing methods and systems for concurrently assessing afferent and efferent visual functions.

Lipoxygenases (LOX) are enzymes that catalyze the peroxidation of certain fatty acids. The cell membrane is mostly made of lipids (which include fatty acids), and peroxidation can cause damage to the cell membrane. The human genome contains six functional LOX genes that encode for six LOX enzyme variants, or isozymes. The role that each LOX isozyme plays in health and disease varies greatly, spanning issues such as asthma, diabetes, and stroke. LOX enzymes are extremely difficult to target due to high hydrophobicity. Potential leads are often ineffective because they are either not readily soluble or not selective for a particular LOX enzyme.  Studies have implicated human epithelial 15-lipoxygenase-2 (h15-LOX-2, ALOX15B) in various diseases. h15-LOX-2 is highly expressed in atherosclerotic plaques and is linked to the progression of macrophages to foam cells, which are present in atherosclerotic plaques. h15-LOX-2 mRNA levels are also highly elevated in human macrophages isolated from carotid atherosclerotic lesions in symptomatic patients. Children with cystic fibrosis had reduced levels of h15-LOX-2, which affects the lipoxin A4 to leukotriene B4 ratio. Furthermore, the interactions of h15-LOX-2 and PEBP1 changes the substrate specificity of h15-LOX-2 from free polyunsaturated fatty acids (PUFA) to PUFA-phosphatidylethanolamines (PE), leading to the generation of hydroperoxyeicosatetraenoic acid (HpETE) esterified into PE (HpETE-PE). Accumulation of these hydroperoxyl membrane phospholipids has been shown to cause ferroptotic cell death, which implicates h15-LOX-2 in neurodegenerative diseases such as Alzheimer’s, Parkinson’s, and Huntington’s diseases.  

Delivery technologies such as lipid nanoparticles (LNP) offer significant advantages over the delivery of free RNA for various RNA therapeutic, vaccine, and basic science applications. UC Berkeley researchers developed a new class of lipid nanoparticle (LNP) which is effective in delivering various types of nuclei acids in different tissues.  The LNP was successfully tested in in-vivo mouse models and therefore poses a significant promise in the gene editing field. The lipid formulation was packaged together with CRISPR Cas9 and a gRNA targeting the endogenous Tau locus. Tau dysrregulation is a pathological feature of Alzheimers disease, thus the invention provides a means to intervene in the development of pathological states associated with Tau aggregate formation. 

Lipoxygenases catalyze the peroxidation of fatty acids which contain bisallylic hydrogens between two cis double bonds, such as in linoleic acid (LA) and arachidonic acid (AA). Lipoxygenases are named according to their product specificity with AA as the substrate because AA is the precursor of many active lipid metabolites that are involved in a number of significant disease states. The human genome contains six functional human lipoxygenases (LOX) genes (ALOX5, ALOX12, ALOX12B, ALOX15, ALOX15B, eLOX3) encoding for six different human LOX isoforms (h5-LOX, h12S-LOX, h12R-LOX, h15-LOX-1, h15-LOX-2, eLOX3, respectively). The biological role in health and disease for each LOX isozyme varies dramatically, ranging from asthma to diabetes or stroke. The nomenclature of the LOX isozymes is loosely based on the carbon position (e.g., 5, 12, or 15) at which they oxidize arachidonic acid to form the corresponding hydroperoxyeicosatetraenoic acid (HpETE), which is reduced to the hydroxyeicosatetraenoic acid (HETE) by intracellular glutathione peroxidases. Lipoxygenase inhibitors are difficult to formulate due to challenges with solubility and other factors, therefore new formulations are needed.

Lipoxygenases form a large family of enzymes capable of oxidizing arachidonic acid and related polyunsaturated fatty acids. One such lipoxygenase, 12/15 LOX can oxidize both the C-12 and C-15 of arachidonic acid, forming 12- or 15-hydroperosyarachidonic acid (12- or 15-HPETE). Lipoxygenases and their metabolites have been implicated in many diseases. In particular 12/15-LOX (also known as 15-LOX-1, 15-LOX, or 15-LO-1 in humans and L-12-LoX, leukocyte-type 12-LO, or L-12-LO in mice) plays a role in atherogenesis, diabetes, Alzheimer's, newborn periventricular leukomalacia, breast cancer, and stroke. Whatever the name, the protein is encoded by the gene ALOX15 in both mice and humans. Lox inhibitors are difficult to develop due to the mouse and human homologs having different substrate and inhibitor specificities - 12/15 LOX produces predominantly 15-HETE in humans and 12-HETE in mice. So existing inhibitors are not selective for 12/15 LOX with regard to other LOX isoforms. In addition, many are strong antioxidants and therefore may result in off-target effects. 

Researchers at UC Irvine have developed an organoid culture system capable of generating three-dimensional molecular gradients. This recapitulates in vivo tissue development more accurately than current two-dimensional organoid culture systems and will allow scientists to study human-specific disease mechanisms in native tissue.

During initial stages of development, the human brain self assembles from a vast network of billions of neurons into a system capable of sophisticated cognitive behaviors. The human brain maintains these capabilities over a lifetime of homeostasis, and neuroscience helps us explore the brain’s capabilities. The pace of progress in neuroscience depends on experimental toolkits available to researchers. New tools are required to explore new forms of experiments and to achieve better statistical certainty.Significant challenges remain in modern neuroscience in terms of unifying processes at the macroscopic and microscopic scale. Recently, brain organoids, three-dimensional neural tissue structures generated from human stem cells, are being used to model neural development and connectivity. Organoids are more realistic than two-dimensional cultures, recapitulating the brain, which is inherently three-dimensional. While progress has been made studying large-scale brain patterns or behaviors, as well as understanding the brain at a cellular level, it’s still unclear how smaller neural interactions (e.g., on the order of 10,000 cells) create meaningful cognition. Furthermore, systems for interrogation, observation, and data acquisition for such in vitro cultures, in addition to streaming data online to link with these analysis infrastructures, remains a challenge.

Researchers at the University of California, Riverside (UCR) in collaboration Nationwide Children’s Hospital  have developed and characterized small peptidomimetics that act as EphA4 agonists. Given ALS is a heterogeneous disease, astrocytes reprogrammed from the fibroblasts of patients with sporadic and SOD1-linked ALS (iAstrocytes) were cultured with MNs and the UCR/Nationwide EphA4 agonists.  As seen in Fig. 1, these small agonistic peptidomimetics decrease MN death in iAstrocytes derived from sporadic ALS (sALS) cells.     

Researchers at UC Irvine have discovered a novel mechanism by which restoration of protective nerve coverings fails in degenerative disease like multiple sclerosis. While therapeutics to slow disease progression exist, there are currently none aimed at preventing or restoring damage to nerve coverings.

Stress and loneliness are biologically toxic factors with adverse effects on mental and physical health. The 2018 Gallup World Poll found a 25%–40% increase in stress, worry, and anger in the US from 2008 to 2018. Loneliness is associated with considerable distress, and older adults are vulnerable to loneliness due to losses, physical decline, and social isolation. The COVID-19 pandemic led to increased social isolation, though some older adults with higher levels of resilience and wisdom faced the pandemic with greater fortitude than younger adults.Aging is associated with numerous stressors that negatively impact older adults’ well-being. Resilience improves ability to cope with stressors and can be enhanced in older adults. Senior housing communities are promising settings to deliver positive psychiatry interventions due to rising resident populations and potential impact of delivering interventions directly in the community. 

Manganese (Mn) is an essential metal that must be maintained at levels within a narrow physiological range in cells and organisms to avoid deficiency or toxicity. Humans can be exposed to elevated manganese levels from occupational sources (e.g., welding) or environmental sources (e.g., drinking water). Elevated manganese levels cause manganese to accumulate in the brain, inducing neurotoxicity that can manifest as parkinsonism. Thus, manganese toxicity is a public health concern and developing ways to treat it is crucial. Based on elucidative manganese homeostasis studies, a UC Santa Cruz researcher, in collaboration with researchers at University of Texas at Austin, has developed methods for treating manganese toxicity.

Neuronal injury is the major pathology caused by CNS injuries like stroke or spinal cord injury. However, currently available biomarkers for CNS injuries are either not expressed in neurons at all, or are expressed constitutively in all neurons, regardless of whether the neurons are injured or not. ATF3 as a CNS injury biomarker is revolutionary because its baseline expression in CNS is very low, and it is rapidly induced only in CNS neurons shortly after CNS injuries like stroke or spinal cord injury.  Of note, human serum ATF3 level can be easily measured by a commercially available ELISA kit.

Researchers at the University of California, Davis have developed a method of treating or mitigating seizure, treating epilepsy, as well as a method of reducing the frequency of seizures, using cannabigerol or dihydrocannabigerol and analogs thereof.

Success of deep brain stimulation (DBS) procedures relies heavily on the precise placement of electrodes. However, current options for learning this specialized procedure are limited to observing live cases, listening to audio recordings, or watching computer simulation videos. Researchers at UC Irvine have developed a first-of-its-kind, physical simulation model that allows for easy, convenient, and realistic demonstration of DBS electrode placement to benefit both medical professionals and patients alike.

Researchers from the University of California, Riverside have developed potent monoclonal antibody inhibitors with high MMP-12 selectivity.  These antibodies have applications in pharmaceuticals and biomedical sciences. Specifically, these antibodies may be developed as  therapies for inflammatory and neurological diseases. Fig 1: Inhibitory function of the MMP-12 antibodies LG4, LH6, and LH11 towards cdMMP-12. 

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Microelectrodes are the gold standard for measuring the activity of individual neurons at high temporal resolution in any nervous system region and central to defining the role of neural circuits in controlling behavior. Microelectrode technologies such as the Utah or Michigan arrays, have allowed tracking of distributed neural activity with millisecond precision. However, their large footprint and rigidity lead to tissue damage and inflammation that hamper long-term recordings. State of the art Neuropixel and carbon fiber probes have improved on these previous devices by increasing electrode density and reducing probe dimensions and rigidity. Although these probes have advanced the field of recordings, next-generation devices should enable targeted stimulation in addition to colocalized electrical recordings. Optogenetic techniques enable high-speed modulation of cellular activity through targeted expression and activation of light-sensitive opsins. However, given the strong light scattering and high absorption properties of neural tissue optogenetic interfacing with deep neural circuits typically requires the implantation of large-diameter rigid fibers, which can make this approach more invasive than its electrical counterpart.Approaches to integrating optical and electrical modalities have ranged from adding fiber optics to existing Utah arrays to the Optetrode or other integrated electro-optical coaxial structures. These technologies have shown great promise for simultaneous electrical recordings and optical stimulation in vivo. However, the need to reduce the device footprint to minimize immune responses for long-term recordings is still present.

Researchers at the University of California, Davis have developed an approach to improve drug delivery to tumors and metastases in the brain. Their multi-barrier tackling delivery strategy has worked to efficiently impact brain tumor management while also achieving increased survival times in anti-cancer efficacy.