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New Method to Enhance Auxin Sensitivity for Improved Crop Productivity

Professors Xumei Chen and Meng Chen at the University of California, Riverside (UCR) have shown the miRNA156’s role in plant growth and productivity. As shown in Figure 1, miRNA156 acts in pathways involved with plant hormones such as auxin and brassinosteroids responsible for plant growth. Exogenous application of miRNA156 potentially in combination with exogenous auxins can be useful in a variety of horticultural contexts for their ability to increase auxin sensitivity and plant growth.    

Add-Seq: Quantitative Genome-Wide, Single-Molecule, And Long-Range Nucleosome Profiling

In cells, DNA is organized by wrapping DNA strands around histone proteins, creating protein-DNA complexes called nucleosomes which comprise the basic unit of chromatin. Chromatin is associated with regions of low gene expression, as compacted DNA is inaccessible to proteins that would promote transcription. Conversely, regions in the DNA not bound by histones experience higher gene expression, as this DNA is readily available to be transcribed.  Nucleosomes are not uniformly positioned on a DNA molecule, and they change based on factors like which genes are expressed during different cellular processes. It is beneficial to understand where nucleosomes are positioned, as this can provide insight into how genes are regulated, or how factors like epigenetic modifications or chromatin structure affect this accessibility and can additionally illuminate gene expression patterns in disease for designing therapies. Nucleosome profiling is a technique used to study the positions of nucleosomes along a DNA molecule. Typically, histones are crosslinked to DNA, then the DNA is fragmented and digested leaving only regions protected by nucleosomes left for short-read sequencing. However, this fragmentation only reveals nucleosome positioning at the resolution of a few hundred base pairs, leaving the larger genomic context of these nucleosome positions to be desired. To address this, researchers at UC Santa Cruz developed Add-SEQ, a pipeline using long-read nanopore sequencing to map nucleosomes across long stretches > 10 kb of single DNA molecules.

System For Continuous Mutagenesis In Vivo To Facilitate Directed Evolution

This invention overcomes a limitation of in vivo mutagenesis systems. Some methods of mutagenesis involve treatment of plasmids with mutagenic chemicals or UV light prior to transformation, but these result in biased mutation spectra. Use of error prone DNA polymerases produces a more random set of mutations, but the rate of mutagenesis rapidly declines with continuous culture. As a result, using such polymerasaes separates mutagenesis and selection into multiple steps. Mutant genes in plasmids need to be generated by the error prone polymerase, then the plasmids isolated into libraries and selected in a separate step. What is needed, then is an error prone DNA polymerase that does not result in a decline in the rate of mutagenesis in culture.  

Methods for Determining Base Locations in a Polynucleotide

An abasic site (i.e., an apurinic or apyrimidinic site) in a DNA or RNA strand is one in which the base is not present, but the sugar phosphate backbone remains intact. UC Santa Cruz researchers discovered that nanopore sequencers can readily detect the positions of abasic sites within a DNA strand during sequencing. This invention capitalizes on this discovery by using enzymes to generate abasic sites at places on a DNA strand that contain modified bases. The DNA strand can then be sequenced using nanopore sequencing, thereby providing a way of detecting modified bases.

Polysaccharide A-Based Particulate Systems For Attenuation Of Autoimmunity, Allergy and Transplant Rejection

Researchers at the University of California, Davis have developed a customizable polysaccharide that can be added to nanoparticles to reduce their rejection by the human immune system.

Compositions and Methods Useful in Promoting Milk Production

The mammary gland is responsible for producing milk in mammals. Producing a milk supply involves significantly accelerated cell growth and differentiation. It is thought that alveologenesis, the process by which milk-producing alveoli are made, occurs when alveolar progenitor cells differentiate into milk-producing alveolar cells. Thus, promoting alveolar differentiation is important in increasing milk production. Various industries, such as the dairy industry, may be interested in increasing milk production generally or increasing milk production without the use of hormones.

(SD2022-092) Cannabinoid production

Brief description not available

Epigenetic Prevention and Treatment of CDKL5 Deficiency Disorder

Researchers at the University of California, Davis have developed a targeted epigenetic approach for the prevention and treatment CDKL5 deficiency disorder.

(SD2022-133) Methods to monitor guanitoxin cyanobacterial blooms

Freshwater is essential for drinking and agriculture, yet potable watersheds are increasingly impacted by the undesirable high-density growth of algae and/or cyanobacteria. Understanding, monitoring, and remediating harmful algal/cyanobacterial blooms (HABs/cyanoHABs) and their associated toxins are essential to reducing their societal impact. Recent scientific and technological advances continue to improve environmental cyanoHAB detection and prediction;  however, the vast cyanotoxin structural chemodiversity creates challenges in their comprehensive detection and quantification using standard analytical chemistry assays. In contrast, quantitative molecular biological detection of biosynthetic genes via PCR provides a multiplexable and cost-effective monitoring strategy to identify the toxic potential of blooms independent of active toxin synthesis. The biosynthetic gene clusters (BGCs) for important freshwater cyanotoxins like microcystin, cylindrospermopsin,  saxitoxin,  and anatoxin-a have been defined and applied toward detection over the past decades. However, the biosynthetic pathway and genes for guanitoxin, the only known natural organophosphate neurotoxin, have yet to be described.Previously known as anatoxin-a(s),  guanitoxin is an irreversible inhibitor of acetylcholinesterase, sharing an identical mechanism of action with organophosphates like the synthetic chemical warfare agent sarin and the banned pesticide parathion. Guanitoxin induces acute neurological toxicity that can lead to rapid death, showing comparable lethality (LD50 = 20 μg/kg i.p.) to saxitoxin, the most potent known cyanotoxin. Sporadic detection in the Americas, Europe, and Middle East coupled with bloom-related animal deaths consistent with guanitoxin exposure suggests that this toxin could be an under-recognized threat in global watersheds. 

Novel Genetic Switch for Inducing Gene Expression

Prof. Sean Cutler and colleagues at the University of California, Riverside have engineered a system and methods to induce gene expression in plants and organisms, including mammals, using the chemical compound mandipropamid. Using the PYR/PYL/HAB1 promoter system, the PYR1/HAB1 system is reprogrammed to be activiated with mandipropamid.  When the PYR1/HAB1 system dimerizes through chemical induced dimerization (CID) with mandipropamid, the system functions as a control switch for gene expression. This technology has been demonstrated to advantageously accelerate citrus breeding.  It may be applied to improve CAR T-cell therapy and agricultural crops. Fig 1: UCR’s PYR1/HAB1 system is programmed through chemical induced dimerization (CID) initiated by mandipropamid to function as a switch for agrochemical control of gene expression.  

Vascular Anastomosis Device

Researchers at the University of California, Davis have developed a surgical device to facilitate vascular anastomosis procedures with enhanced ease and speed.

Deep Learning-Based Approach to Accelerate T cell Receptor Design

Researchers at the University of California, Davis have developed a deep learning simulation model to predict mutated T-cell receptor affinity and avidity for immunotherapy applications.

Positive Allosteric Modulators Target TRPV1 with Analgesic Effects

Researchers at the University of California, Davis have developed de novo positive allosteric modulators (PAMs) that bind to TRPV1 proteins involved with pain-sensing in order to provide analgesic effects.

Reinforcement Learning with Real-time Docking of 3D Structures for SARS-COV-2

The inventors propose a novel framework generating new molecules that potentially inhibit the Mpro protein, the main protease of SARS-COV-2. The technology combines deep reinforcement learning (RL) with real-time molecular docking on the 3d structure of Mpro using AutoDock Vina, an open-source program for doing molecular docking. A second second docking software, Glide, was used to validate the generated molecules. The AutoDock and Glide docking softwares showed consensus on 41 molecules as potential potent Mpro inhibitors that were sufficiently easy to synthesize. The inventors show that this method samples the drug chemical space efficiently, covering a much broader space than molecules submitted to the COVID moonshot project, and the molecules have the correct shape and non-bonded interactions to fit into the binding pocket. Moreover, this approach only relies on the structure of the target protein, which means it can be easily adapted for future development of other inhibitors.

Synthetic Biology Methods and Systems to Synthesize Strigolactone

Prof. Yanran Li and colleagues from the University of California, Riverside have developed a biosynthetic method for producing different strigolactones by designing different biosynthetic pathways in engineered microbial systems. The invention includes engineered E. coli - S. cerevisiae co-culture systems for the biosynthesis of both non-canonical and canonical SLs, including but not limited to carlactone (CL), carlactonic acid (CLA), 5-deoxystrigol(5DS), 4-Deoxyorobanchol (4DO) and orobanchol. This technology allows SLs to be biosynthetically produced in large scale for use in innovative  agrochemicals such as phyto-regulators,  fertilizers, biostimulants that enhance the nutrient uptake efficiency. Fig 1: Mimicking plant strigolactone pathway distribution in the engineered E. coli-S. cerevisiae coculture.

Inter-Brain Measurements for Matching Applications

This technology utilizes inter-subject measurement of brain activity for the purpose of matching individuals. In particular, the invention measures the similarity and differences in neural activity patterns between interacting individuals (either in person or online) as a signature measurement for their matching capabilities. Relevant applications can be in the world of human resources (e.g., building collaborative teams), patient-therapist matching and others. The application relies on the utilization of both custom and commercial devices for measuring brain activity.

Aluminum Microchips for Biosensing and Pathogen Identification

Prof. Quan Cheng and colleagues from the University of California, Riverside have developed aluminum (Al) microchips for highly sensitive SPR detection of bioanalytical targets. This technology allows for determination of binding kinetics of drug targets and disease marker detection. In addition to applications for SPR, these Al microchips enable other surface-based techniques such as enhanced Raman spectroscopy and MALDI-MS for direct pathogen identification. Compared to traditional gold substrates, Al has a broad range of advantages. It is more plasmonically active, leading to high optical sensitivity, and it is chemically flexible for design of various analytical platforms. Al also has several manufacturing benefits that make it commercially appealing when compared to gold, such as higher abundance, lower cost, and simple integration into existing manufacturing processes such as CMOS. Fig 1: (Top) Fabrication of aluminum microchips. (Bottom) Aluminum demonstrates a high theoretical and practical plasmonic activity correlating to a higher detection sensitivity for biological targets.  

Plasmonic Gold Microchips for Swift Microbial Identification with MALDI-MS

Prof. Quan Cheng and colleagues from the University of California, Riverside have developed a gold microchip consisting of a nanoscale film fabricated on a gold substrate for highly effective, matrix-free laser desorption ionization mass spectrometry (LDI-MS) analysis of lipids. This technology allows for effective analysis of low mass metabolites without the need for time consuming extraction methods. The microchip also enhances fluorescent signal through metal enhanced fluorescence (MEF) allowing single cells to be located easily and improves ionization of lipids. Fig 1: Gold microchips enable localization of cells with MEF and efficient ionization of lipid species. The lipid fingerprint can then be used to trace changes caused by toxicants or identify microbial species present.  

One-Pot Multienzyme Synthesis of Sialidase Reagents, Probes and Inhibitors

Researchers at the University of California, Davis, have developed an environmentally friendly one-pot multienzyme (OPME) method for synthesizing sialidase reagents, probes, and inhibitors.

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