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Enhancement of Immune Response to Porcine Reproductive and Respiratory Syndrome (PRRS) Vaccine by Interferon Alpha Porcine reproductive and respiratory syndrome (PRRS) is a major problem for hog farmers worldwide. PRRS is caused by a virus which leads to reproductive failure in... Read More Porcine reproductive and respiratory syndrome (PRRS) is a major problem for hog farmers worldwide. PRRS is caused by a virus which leads to reproductive failure in sows and respiratory problems in piglets and growing pigs. The PRRS virus spreads rapidly, leading to large economic losses for farmers and overall lower health for pigs. Currently, PRRS is controlled by inoculating pigs with modified live virus which stimulates the immune system of pigs against the PRRS virus. However, this therapy does not prevent PRRS virus infection and is limited by individual pigs ability to create a strong immune response against the vaccine. The current technology is a composition and method for use that enhances the immune response to PRRS vaccine for the purpose of improving the vaccines efficacy against the PRRS virus. One of the challenges with PRRS is that the PRRS virus is resistant to pigs natural immune response. The PRRS virus is able to hide from the natural defense system by being resistant to signals that alert the body of the viruses presence. Interferon-a is one such alert signal that PRRS virus fails to up-regulate. The current technology uses plasmids (or related technologies) to increase interferon-a production during administration of modified live virus vaccine. By doing so, interferon-a interacts with T cells to create virus specific interferon-? secreting cells. The result is a robust immune system response to the vaccine which should strengthen the immune systems ability to fight infection of PRRS virus. Applications Can be used as a supplement to PRRS vaccines for swine Has broad application for hog farmers and veterinary clinics Benefits Strengthened immune system: In vivo application of interferon-a and modified live virus to pigs resulted in over 3x as many virus specific interferon-? secreting cells as modified live virus application alone Reduction in abortion/still births: Amount of PRRS virus specific interferon-? secreting cells is positively correlated with reduction of abortion/still births in sows
Therapeutic Scheme for Human Basigin Cancer researchers are focusing their efforts on identifying central pathways that trigger or enhance the invasiveness of tumor cells. One such target is EMMPRIN (... Read More Cancer researchers are focusing their efforts on identifying central pathways that trigger or enhance the invasiveness of tumor cells. One such target is EMMPRIN (Extracellular Matrix Metalloproteinase Inducer). It has been shown that EMMPRIN expression is linked to various cell signaling pathways that lead to an increase in tumor cell vascularization. Researchers are focusing efforts on elucidating the role of EMMPRIN in a number of disorders including cancer, arthritis, tissue repair and numerous inflammation-dependent diseases. DESCRIPTION/DETAILS Basigin is a member of the immunoglobulin superfamily thatis also known as EMMPRIN. Human basigin is expressed as two differentiallyspliced isoforms encoded by a single gene found on chromosome, renamedrespectively as basigin-1 and basigin-2. Attempts to demonstrate specifichemophilic on separate cells, or between soluble forms of recombinant basiginusing surface Plasmon resonance have not been successful, suggesting thatbasigin-2 cannot function as a receptor for itself. In order to identify possible receptors for soluble basiginligand, an affinity purification approach was employed. This approach resulted inthe labeling of several potential interacting proteins, and MALDI MS/MSsequencing of one of these proteins identified a novel isoform of human basigin(basigin-3). Immunoprecipitation studies using cell fractions revealed thatrBSG interacts with basigin-2 at the cell membrane, and subsequently interactswith the basigin-3 isoform within the cell. Small-interfering RNA (siRNA)knockdown of basigin-2 protein reduced, but did not eliminate, rBSG-mediatedERK activation in HESCs, suggesting that additional cell surface receptors forsoluble basigin may exist. Taken together, these results support the hypothesisthat basigin-2 can function as a receptor for soluble basigin and demonstratethat the hemophilic interactions between basigin proteins are not dependentupon glycosylation of the basigin ligand. It has also been shown that soluble EMMPRIN binds tomembrane-bound EMMPRIN and the bound complex is internalized presenting apotential means to deliver therapeutic compounds to the cell in a highlytargeted manner. A therapeutic scheme isproposed that aims to design EMMPRIN-conjugates designed to deliver cancertherapeutics in a targeted fashion. Applications Conjugation oftherapeutics to EMMPRIN increases specificity and targets cancers cells cancer (skin, bladder,breast); other inflammatory diseases (arthritis, endometriosis); Upregulationof inflammatory response. Benefits It is possible to design therapeutic agents directed toward human basigin. Possible therapeutic scheme to block tumor progressionor inflammation.
Integrated Portable Pneumatically Powered Ankle-Foot Orthosis Below the knee muscle weakness, defined by weak dorsiflexor (shin) or plantarflexor (calf) muscle groups, can result from a variety of physical impairments or... Read More Below the knee muscle weakness, defined by weak dorsiflexor (shin) or plantarflexor (calf) muscle groups, can result from a variety of physical impairments or congenital abnormalities. Stroke, spinal cord injuries, polio and multiple sclerosis are among some of the physical injuries and congenital defects responsible for the condition. The largest complication from below the knee muscle weakness is abnormal gait, which when compensated for can lead to further complications in other muscles and joints. Ankle-foot-orthoses (AFOs) have been designed to assist afflicted individuals in walking and rehabilitation of the weakened muscle groups. Unfortunately, many commercially available AFOs are passive devices that cannot provide assistance during the propulsive phase of gait. Furthermore, these instruments are not capable of adapting to changes in walking conditions. Powered AFOs have been engineered to overcome these limitations but lack practicality in that they are commonly tethered to off-board power sources. This technology provides a non-tethered, portable pneumatic powered AFO that controls and assists propulsion of the foot as well as ankle motion using plantarflexor and dorsiflexor torque at the ankle joint. A custom-built pneumatic rotary actuator is located at the ankle joint. Torque generated by the actuator is used for both motion control of the foot and to provide supplemental torque for the individual during gait. Pressure regulators are used to manage the force produced by the rotary actuator and valves are used to direct the flow of fluid power to the actuator. Control and sensing of the actuator is accomplished through use of pressure and angle sensors and onboard electronics. Applications This device can be used to aid individuals afflicted with below the knee muscle weakness or impaired gait resulting from any number of physical injuries or congenital disabilities. Portability of the device permits the device to be used in a variety of locations. Applications include: Assistance in walking (including flexibility to walk outside) Relief from pain and discomfort during walking Rehabilitation of dorsiflexors and plantarflexors (possible from the patients personal residence) Benefits The portable pneumatic AFO is beneficial compared to passive AFOs in that it: Controls velocity of foot during initial contact to prevent foot-slap Provides torque at end of the stance for propulsion Supports the foot in the neutral, 90 degree position during swing to prevent foot-drop and allow free range of motion throughout the walking cycle Enables full customization of timing and magnitude of assistance through electronic and mechanical means Benefits over other powered AFOs include: Portable, non-tethered power
A DNA-Based Diagnostic Test for the Identification of Individuals having the Mutation causing the Ectodermal Dysplasia (ED) Genetic Defect in Sheep Researchers from the University of Illinois have identified a new inhibitor of the androgen receptor (AR), CPIC, that would be effective in the treatment of... Read More Researchers from the University of Illinois have identified a new inhibitor of the androgen receptor (AR), CPIC, that would be effective in the treatment of Castration Resistant Prostate Cancer (CRPC). CPIC targets a novel site on the full-length and truncated forms of the AR, present in the CRPC. Initial in vivo data has demonstrated that this new class of compounds is capable of inhibiting growth of prostate cancer cells. Furthermore, CPIC has shown to be 40x more potent against the truncated AR compared to current small molecules against the truncated AR.
Biosynthesis of Lantibiotics: In vitro semi-synthetic production methods for generation of industrial antibiotic, Lacticin 481 This invention allows the engineering of semi-synthetic lantibiotics to a much larger extent than using typically practiced in vivo methods. The method is the... Read More This invention allows the engineering of semi-synthetic lantibiotics to a much larger extent than using typically practiced in vivo methods. The method is the first in vitro reconstruction lantibiotic photosynthesis and introduces non-proteinogenic amino acids. Lantibiotics are peptide-based compounds produced by bacteria that live on lactic acid. They are used as natural antibiotic food preservatives as an alternative to chemical reagents and have been used for half a century without any significant signs of lantibiotic-resistant bacteria popping up. Researchers at the University of Illinois have isolated and purified the LctM enzyme, responsible for synthesis of lacticin 481. This approach, the first in vitro reconstruction of lantibiotic biosynthesis, allows for lantibiotic engineering and opens the door to possible generations of new lantibiotics with greatly increased yields and improved activities. Applications Food preservation Industrial enzyme production Bioengineering of novel lantibiotics Benefits Greater Production Flexibility: In vitro methodology allows for lacticin 481 production using semi-synthetic substrates. Avoids Complications of In Vivo Production: In vitro methods avoid product cytotoxicity, degradation and bypasses many of the In vivo regualtory complications. Better Resistance Profile: Lantibiotics have been used for half a century in more than 40 countries without any significant signs of lantibiotic-resistant bacteria appearing. More Possibilities: The method works well with combinatorial techniques, increasing the number of substrates that can be used in production of lacticin 481. In addition, isolation of the LctM enzyme allows for more efficient synthesis with greater structural and functional tolerance of the biosynthetic pathway.
Ionizable Isotopic Labeling Reagents for Relative Quantification Liquid chromatography/mass spectrometry (LC/MS) is increasingly being used for metabolic analysis due in part to its widespread availability and compatibility with... Read More Liquid chromatography/mass spectrometry (LC/MS) is increasingly being used for metabolic analysis due in part to its widespread availability and compatibility with biological samples. This invention provides ionizable, isotopic labeling reagents and labeling reaction products, answering the current need for relative quantification using mass spectrometry. Absolute quantification of an analyte relies upon the addition of an internal standard differing only in its isotopic form. However, it is impractical to add an isotopic standard for every compound when performing more comprehensive metabolic profiling. Relative quantification between samples is more amenable to analyzing broad classes of compounds, and it often provides very useful biological information. Heavy and light isotopic forms of methylacetimidate have been synthesized and used as labeling reagents for quantification of amine-containing molecules, such as biological samples. Heavy and light isotopic forms of formaldehyde and cholamine have also been synthesized and used independently as labeling reagents for quantification of amine-containing and carboxylic acid-containing molecules, such as these found in biological samples. Advantageously, the labeled end-products are positively charged under normal acidic conditions involving conventional liquid chromatography mass spectrometry (LC/MS) applications. This invention improves the precision of relative quantification by minimizing or negating errors associated with run-to-run irreproducibility. Such errors can arise from variations in mass spectrometric detection sensitivity, such as those caused by ionization suppression in electrospray, or from retention time differences between runs. The isotopic pair of labeled compounds co-elute within a single run. Therefore, they have identical retention times and are electrosprayed from identical solution conditions.
Gene Cluster Capable of Enabling the Biosynthesis of the Antimicrobial Compound, Rhizocticin In Bacillus subtilis Phosphonic and phosphinic acids are bioreactive compounds that have been used as antibiotics, antifungal agents, antimalarial drugs, and herbicides. Rhizocticins... Read More Phosphonic and phosphinic acids are bioreactive compounds that have been used as antibiotics, antifungal agents, antimalarial drugs, and herbicides. Rhizocticins are naturally occurring phosphonates produced by Bacillus subtilus that have antifungal properties and interfere with the biosynthesis of the amino acid threonine. By varying the N-terminal amino acid group in the rhizocticin compound, it is possible to alter its biological activity. In particular, oligopeptides that are created by varying this amino acid could potentially allow enhanced capability for controlling selectivity for targeting particular organisms. As a result, compounds are less toxic to the host species and hold more promise for creating therapeutics. Despite the potential for making these types of compounds, organic synthesis has never been achieved due largely in part to the fact that the biosynthetic pathway has not been well understood. University of Illinois scientists have now identified the gene cluster responsible for biosynthesis of rhizocticin in B. subtilis, making biosynthesis of rhizocticin compounds possible. Details Original attempts to isolate and identify this unquie cluster failed, however, the genome of a specific strain of B. subtilis was sequenced and open reading frame locations were determined and annotated. Upon comparison with a non-rhizocticin-producing strain of B. subtilis, the rhizocticin biosynthetic gene cluster was able to be identified and isolated. There are more than 10 genes in the B. subtilis rhizocticin cluster. The biosynthetic pathway was proposed using sequence homology (similarity) for each of the genes. One particular gene in the cluster was identified by the inventors as being unique to this biosynthetic pathway. The cluster responsible for rhizocticin was verified by successfully inserting it into a non-producing strain of B. subtilis. Applications Pharmaceutical industry: Synthesis of biologically active compounds and analogs of rhizocticin. Production of novel oligopeptides with therapeutic properties Agricultural industry: Herbicide Benefits The identification of specific gene cluster for biosynthesis of rhizocticin allows: Specific synthesis of compounds; Control of biological activity of compounds; and Control of compound toxicity in mammals
New 3D Gels for Cell Culture and Therapy Researchers from the University of Illinois have created a new porus 3D gel. This gel can be prepared with a variety of natural or synthetic polymers and can also... Read More Researchers from the University of Illinois have created a new porus 3D gel. This gel can be prepared with a variety of natural or synthetic polymers and can also contain growth factors or other cellular signaling molecules to improve 3D cell culturing. This technology has the potential to be used in many novel techniques including stem cell therapy, organ and skin transplants as well as many research technologies and other medical processes.
Lantibiotic Screening Technique Dr. van der Donk has developed a screening system for identifying novel antibiotics. The system uses phage display and has been optimized for lantibiotic natural... Read More Dr. van der Donk has developed a screening system for identifying novel antibiotics. The system uses phage display and has been optimized for lantibiotic natural products. The system also has utility for investigating interactions between lantibiotics and other peptides. Lantibiotics have complex structures which make them particularly stable under changing pH and protease exposure as well as possessing the ability to bind to bacterial cell wall targets. This makes them ideal for scaffolds for new antibiotic discovery that can combat the burgeoning problem of antibiotic resistance
New Synthetic Tumor Microenvironments Researchers from the University of Illinois have developed a new synthetic tissue microenvironment that may give cancer researchers the next-best look at tumor... Read More Researchers from the University of Illinois have developed a new synthetic tissue microenvironment that may give cancer researchers the next-best look at tumor growth and behavior. The 3D patterned vasculature tumor microenvironment is created by changing the flow rates of fluid channels and the structures are made of alginate that was mixed with breast cancer cells in the outer layer and macrophages on the inner layer. The 3D vascularization, a network of capillaries that carry drugs and other materials are created can go from straight, to snakelike, to any shape, that offers modelling for metastasis, because the vessel architecture can be tuned on the ﬂy. The technology accurately predicted the clinically measured EC50 of three drugs: Gefitinib, zoledronic acid, and RAC inhibitor. This quick process to create synthetic tumor microenvironments lends to tremendous potential such as model systems for high-throughput screening for drug efficacy, as well as flowable and vascularized lab-on-a-fiber platforms. Finally, biopsied cancer cells lends to personalized cancer treatments with this device that could realistically and quickly recreate microenvironments found across biology.

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