Automatic MRI Quantification of Structural Brain Abnormalities

This invention enables the automatic detection of brain areas that are abnormally small or large. The diagnosis of many neurological diseases rely on the visual detection of areas in the brain that are abnormally small. With this technique, one may be able to map the locations in the brain where there is a difference in brain tissue compared to the normal population. The quantification through the use of Z-scores enables the observer to gauge how abnormal this area is compared to a standard. While this technique does not specifically diagnoses a disease, it may help the clinical judgement of MRI images.

Plasma Protein Biomarkers for Exposure to ROS/RNS & Drugs That Cause ROS/RNS

Disclosed is the identification of four separate plasma protein biomarkers found to be S-glutathionylated upon exposure to a formulation containing oxidized glutathione (NOV-002), along with a method for detection of the modified proteins.  S-glutathionylation is a reversible reaction in which glutathione is bound to a cysteine residue on a target protein and occurs in response to oxidative stress.  Oxidative stress can be toxic and can be induced by the administration of certain drugs, particularly anticancer agents such as Cisplatin, Busulfan and others.  Therefore, these biomarkers will be useful in monitoring the oxidative stress produced by anticancer agents as well as the pharmacological activity of S-glutathionylation-inducing agents such as NOV-002.

Investigators at the Medical University of South Carolina performed both in vivo and ex vivo studies with mice using NOV-002.  Mice were administered NOV-002 intravenously and plasma samples were recovered.  Upon analysis of the samples four proteins were found to be S-glutathionylated, and their identities were characterized.  In further studies plasma was removed from the animals and treated ex vivo with NOV-002.  It was confirmed that the same proteins were modified in this set of experiments as well.

A Peptide that Disrupts Hsp90:HIF Protein-Protein Interactions as a Therapeutic Treatment for Renal and Other Types of Cancer

Hypoxia inducible factor (HIF) is a heterodimeric transcription factor that regulates the expression of proteins involved in angiogenesis, glucose metabolism, and cell survival.  It is composed of two subunits, one of which is dynamically expressed (a) and one of which is constitutively expressed (ß) (see figure).  HIFa is stabilized in low oxygen conditions, is over-expressed in many solid tumors as a result of the hypoxic environment, and is associated with a poor prognosis.  HIFa is also a client protein for the molecular chaperone heat shock protein (HSP90).  Inventors at the Medical University of South Carolina have previously shown that pharmacologic inhibitors of Hsp90 deplete Hsp90 levels, interfere with HIF-1-mediated transcription, and antagonize angiogenesis.  It has been previously reported that HSP90 binds to the PAS-domain of HIFa.  This domain is found in several proteins and is involved in sensing and responding to changes in the cellular environment.  Conformational changes in PAS domains alter protein-protein interactions, leading to distinct signaling cascades. 

 

Disclosed here, includes the finding that Hsp90 binding in this region of HIF serves a role as a critical mediator of HIF binding partners and subsequent activity.  These inventors have developed a peptidic-based experimental approach to allow identification of the specific HSP90 binding region within this domain.  This strategy will allow our researchers to determine the dependence of HIF-1 and HIF-2 function upon Hsp90 and to understand the dynamics between HSP90 and regulatory proteins binding within the PAS domain.  Finally, this approach may lead to the development of a HIF inhibitor, which may have therapeutic potential.

New Biomarker for Diabetic Vascular Disease

Despite considerable advances in the treatment of type I diabetes, cardiovascular complications remain the primary cause of death and accounts for the greatest component of health care expenditures in people with diabetes. However, the risk factors for developing cardiovascular disease in diabetics remain undefined, until now. Researchers at the Medical University of South Carolina recently discovered a blood plasma biomarker in type I diabetes patients, that, when elevated, indicates an elevated risk of diabetic vascular disease.

A recent study was conducted based on cross-sectional data generated from the Diabetes Control and Complications Trial (DCCT) / Epidemiology of Diabetes Interventions and Complications (EDIC)-cohort of type 1 diabetic patients. An independent association was found between the biomarker levels in blood plasma of diabetics and microalbuminuria (an early indicator of renal dysfunction), hypertension, and elevated lipids. Furthermore, multivariable regression analysis provided the first evidence of an independent and positive association between the biomarker levels and surrogate markers of atherosclerosis in diabetics.

In addition, a novel single nucleotide polymorphism (SNP) in the coding region of the biomarker gene was identified. Survival analyses demonstrated that the onset of microalbuminuria occurs at a more rapid rate in diabetic subjects with the SNP than without the SNP.

Finally, the researchers discovered a novel mechanism by which the biomarker is thought to contribute to vascular inflammation/ endothelial dysfunction: The biomarker stimulates MAPK phosphorylation, independent of bradykinin signaling, and induces apoptosis of vascular smooth muscle cells. As a result, atherosclerotic plaques become instable, enhancing the risk of plaque rupture with subsequent myocardial infarction, organ failure, or stroke.

New Biomarker for Diabetic Kidney Disease

Diabetic nephropathy is the leading cause of end stage renal disease in the Western world and develops in about one-third of diabetic patients.  Although, several established risk factors such as duration of diabetes, hyperglycemia and hypertension have been shown to increase the risk to develop nephropathy, they do not solely account for the incidence and progression of diabetic nephropathy. Rather, there is growing evidence that the risk to develop diabetic nephropathy is in large part genetically determined. Although the evidence for genetic susceptibility in the pathogenesis of diabetic nephropathy is well-recognized, the causative genes remained to be identified.

Connective tissue growth factor (CTGF) is known to be an important risk factor in diabetic nephropathy.  CTGF is increased in diabetic nephropathy and correlates with the degree of albuminuria (leaking of albumin into urine, an early indicator of renal dysfunction). Researchers at the Medical University of South Carolina recently discovered a novel single nucleotide polymorphism (SNP) in the promoter region of the CTGF gene that predisposes diabetic subjects to develop albuminuria (an early indicator of kidney dysfunction). The researchers conducted a study based on cross-sectional data generated from the Diabetes Control and Complications Trial (DCCT) / Epidemiology of Diabetes Interventions and Complications (EDIC)-cohort of type 1 diabetic patients.

The novel CTGF SNP is associated with a 3-fold increased risk to develop albuminuria compared to diabetic patients without the SNP. Survival analyses demonstrated that the onset of albuminuria occurs at a more rapid rate in diabetic subjects with the polymorphism than without the polymorphism. Functional studies show that the basal activity of the mutant was significantly higher than wildtype. The novel SNP is located in one of the Smad 1 binding sites and functional analyses indicate that this region is critical for Smad1-dependent transcriptional regulation of the CTGF gene.

Fluidic Interconnection System for Microfluidic Devices

The technology described here consists of a design for a "genderless" connector for microfluidic devices that can be used either to directly interconnect devices or to make external connections to devices.  There is a rapidly increasing work in the development of microfluidic devices in multiple fields including analytical systems, chemical process microreactors, and systems for manipulation and study of biological cells.  In spite of major activity in microfluidic device development, a generally applicable standard approach to connecting these systems with one another and with the outside world has yet to emerge. 

This interconnection is extremely cost effective, and can easily be incorporated into existing devices without a major investment in additional engineering.  As such, this interconnection system should facilitate further development of microfluidic systems.

Hypertrophic Non-Failure Mouse Model

Different forms of heart enlargement (hypertrophy) with different "active gene profiles" are caused, for example, during endurance training (healthy) or narrow/stenosis of the arteries (heart failure risk). The inventors generated a genetically modified mouse with a hypertrophic heart that responds to surgically-induced arterial stenosis with further hypertrophy, but without anticipated heart failure. Since hypertrophic heart disease comprises up to 70% of cardiovascular diseases (2 of 5 deaths in the United States), understanding the active gene profile in these mice should lead to the development of drugs to prevent heart failure and save lives.

Nkx-2.5 based mouse and in vitro models of cardiogenic lineages

The invention includes a transgenic mouse model and mouse-derived stem cells that are genetically market to express assayable protein markers in the developmentally important early and intermediate staged heart precursor cells. The transgenic reporters used are based upon control regions of the chick (Gallus gallus) Nkx2.5 gene, which is expressed predominantly in precardiac mesoderm destined to become heart and in developing heart in the mouse embryo.

Using the noted reporter fragments, the researcher has designed the following research tools; mouse lines that express betagalactosidase (LacZ), enhanced green fluorescent protein (GFP) and the bacteriophage-derived cre (Cre-Lox) recombinase in distinct cardiogenic lineages of the developing mouse heart.

ob/ob TLR4 Knockout Mouse

Medical University of South Carolina Researchers have created a knockout mouse with the ob/ob and lack of TLR-4 expression phenotype.  There have been a number of studies linking obesity with an increase in TLR-4.  This novel knockout mouse allows researchers to study the effects of obesity and TLR-4 in the outcome of transplants as well.  The mouse is on a BL/6 background, and both ob/ob and lean counterparts are produced to act as proper experimental controls.

Monoclonal Antibodies Reactive to White Spot Syndrome Virus (WSSV)

White Spot Syndrome Virus (WSSV) is a highly pathogenic and prevalent virus affecting crustacea. A number of WSSV envelope proteins, including vp28, have been proposed to be involved in viral infectivity based on the ability of specific antibodies to attenuate WSSV-induced mortality in vivo. A monoclonal antibody which binds to vp28 has been created.

Electrically Controlled Valves for Microfluidic Systems

The invention is a new type of valve for use in "microchip" or "lab-on-a-chip" analytical systems. The valve does not involve any moving parts; therefore, it does not require any new or expensive manufacturing technology. The chip is still made with the same processes used to put the other microfluid handling channels on the chip.

Production Increase of natural and Hybrid Natural Products Produced by a Fermentable organism such as Bacteria or Fungi through Cofermentation with a Selected Second Natural Organism, such as a Bacterium or a Fungus

Investigators disclose a method of increasing the fermentation yield of certain compounds from natural or genetically modified bacteria or fungi without requiring additional energy inputs. The ideal embodiment of the invention may be when the desired product is an antibiotic.

Perfusion Accessory for High-Aspect-Ratio Simulated Microgravity Cell Culture Chambers

Detailed drawings on file at MUSC, and can be obtained once a CDA is in place. The perfusion accessory (PA) for high-aspect-ratio (HAR) simulated microgravity cell culture chambers permits uninterrupted vessel perfusion with fresh culture medium, thereby eliminating the need for periodic replacement or replenishment of vessel culture medium.

CaSm-A Gene Controlling Transformation in Cancer Cells

This invention combines the advantages of attenuated total reflection (ATR) for examining protein-lipid interactions, protein structure and protein orientation with captive bubble surfactometry (CBS) which measures surface active properties of proteins, lipids, and protein/lipid mixtures. This invention will permit simultaneous measurement of protein structure and function at an air/water interface. The ATR-CBS will be able to determine critical surfactant components necessary for pulmonary surfactant replacement therapy of respiratory distress syndrome in premature infants and for therapy of acute respiratory distress syndrome in children and adults.

High Through-Put Assay for Screening Phospholipase D Inhibitors

The invention is an assay system for rapid screening of potential inhibitors of phospholipase D (PLD). This is a new process with many significant improvements over current assays.

 

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