Researchers at the University of California, Davis campus have developed a method to enhance the efficiency of reprogramming a non-pluripotent, somatic cell to a pluripotent stem cell. (more...)

Brain AVM (bAVM) is an important cause of intracranial hemorrhage (ICH) where, nearly half of bAVM patients present with ICH. Cerebral AVMs are most commonly discovered in young adults aged 20-40 years therefore when one considers management of a young patient with a brain AVM, the lifetime risk of hemorrhage can be substantial. Furthermore, our ability to predict which AVMs will rupture remains poor. Aside from hemorrhage, AVMs also present several other symptoms including seizures, headaches, and progressive focal neurological deficits such as weakness, numbness, and vision changes. Currently available therapies, such as, surgical resection, embolization and stereotactic radiotherapy have potentially high treatment-related morbidity.  About 20% of patients are currently not offered treatment due to excessive risk associated with the modalities. There is also considerable controversy regarding unruptured bAVMs being treated by invasive modalities, as treatment risk may outweigh the natural history risk of spontaneous rupture. There is a paucity of safe, effective and non-invasive therapy for brain AVM patients.  (more...)

Attenuated, or weakened, viruses have played a significant role in the development of vaccines, such as the current vaccine for tuberculosis. Viruses undergo genetic change through mutation and recombination of their genetic material, the result of which may be either an increase in pathogenicity or the initiation of an immune response within the host organism. For example, point mutations have been used in the development of attenuated viruses for respiratory vaccines to allow for greater phenotypic stability of the viral vaccine. Current vaccines are typically systemic in nature and are not targeted to a specific tissue within the body. The development of a tissue-specific vaccine could hold significant promise in the development of new treatments for cancers or for the generation of targeted immunity.   Viruses also play an important role in the developing field of gene therapy. Viruses have been used to introduce and target replacement gene sequences to specific tissues to replace defective ones. Viruses are uniquely suited to this as they naturally infect host cells and integrate their genetic material with that of the host cell. (more...)

The method is a novel and convenient method to chemically modify the exterior surface of enveloped viruses so that such viruses can be easily purified. This chemical modification on the envelope of the virus is reversible. (more...)

Epilepsy, a brain disorder in which a person has repeated seizures over time, can severely affect a person’s quality of life. The onset of the epileptic seizures generally begins between the ages of 5 and 20, although the condition can strike people at any age. Epilepsy is generally a lifelong condition that may require surgery or medication. In general, there is no known way to prevent epilepsy. New methods for the prevention and therapy for epilepsy and other neurological disorders will be very useful for those that are currently suffering or may suffer from these debilitating disorders.Researchers at the University of California, Irvine have developed a new method for the prevention and therapy for epilepsy and other neurological disorders. This method can be used to prevent the onset of epilepsy caused by insults (i.e., bodily injury, irritation, or trauma). (more...)

The ability to optically apply input signals and reconfigure existing gene circuit connections would be transformative for engineering functional gene circuits in complex, naturally occurring living systems. To date, current optical methods to interface living cells have so far relied on genomic modifications to permanently encode living cells with light responsive genes, thus limiting dynamic circuit reconfiguration. On-demand optical circuit reconfiguration can be enabled by resonant optical nanoantennas (herein referred to as biomolecular nanoantennas) functioning as selectively addressable optical receivers and biomolecular emitters of small interfering RNA (siRNA). Researchers at the University of California, Berkeley have for the first time reported the design and implementation of photonic gene circuits constructed using biomolecular nanoantennas as optical inputs to existing circuit connections of living cells. They show that photonic gene circuits are modular, enabling sub-circuits to be combined to form large-scale circuit configurations. (more...)

 The agouti-related protein (AgRP) is produced in the brain and is a potent appetite stimulant. The normal 50 amino acid polypeptide is produced in the hypothalamus and binds with high affinity to the melanocortin 3 and 4 receptors (MC3R and MC4R). Along with alpha-melanocyte stimulating hormone (apha-MSH) and neuropeptide Y, AgRP plays a central role in the regulation of mammalian feeding and metabolism. From intracerebroventricular (ICV) injection studies, AgRP is well documented to enhance feeding for one to two days following a single injection, and is probably longer acting than any other known hormone or drug.  (more...)

Ligand binding to the surface of drug carriers has been explored as a way of enhancing targetability and overall efficiency of drug delivery and imaging applications. Multivalent binding to imaging agents has been investigated and has been demonstrated to increase targeting over monovalent binding. However, multivalent ligand binding to enhance targeting of drug-loaded nanoparticles has not been investigated. Therefore, there is a need to investigate the effect of multivalent binding to drug-loaded nanoparticles. (more...)

A mutant tRNA has been developed for use against HIV-1 integration. Studies indicate that this novel tRNA selectively interrupts viral integration into the genome by targeting key steps in this pathway. Most other contemplated therapeutic approaches act after the virus has integrated into the host cells DNA and may be less effective once infection is established. A therapeutic strategy would entail introduction of the mutant tRNA into cells typically targeted by HIV-1. One approach would use a viral vector to infect the target cells and to insert genes that code for the mutant tRNA. Once the mutated tRNA is in the cell, a number of very specific actions could potentially impair viral integration. The mutant tRNA has high affinity to the HIV-1 reverse transcriptase mRNA, making this an ideal therapeutic approach with low toxicity. (more...)

The "ciliopathies" are a newly emerging group of diseases due to defects in the function or structure of cellular primary cilia, which are small cellular appendages previously of unknown function. UC San Diego researchers and colleagues have identified five genes for Joubert Syndrome (JS), which is a ciliopathy that is characterized by cerebellar ataxia, blindness, renal failure, and mental retardation. Most of these mutations occur randomly throughout the gene, which makes genetic diagnosis very laborious. Researchers found that all Jewish patients with JS share a common mutation in a newly identified gene. Of the Jewish families tested thus far, 100 percent of the patients were homozygous for the point mutation. It is anticipated that this discovery will make it possible to perform genetic testing in this population easily. (more...)

UCSD researchers have developed a gene therapy for preventing the blindness and correcting the deafness associated with Usher 1B Syndrome, an inherited recessive loss-of-function disorder caused by mutations in the myosin VIIa gene. These patients are born deaf, and later develop retinal degeneration (retinitis pigmentosa) in their teens. The method utilizes state-of-the-art recombinant lentiviral technology and incorporates full-length human Myosin VIIa cDNA, as well as promoters to direct the expression of the gene. (more...)

Researchers at the University of California, Irvine, have developed a method for the computational optimization of DNA sequences that encode their own correct self-assembly. (more...)

Stem cell therapy holds the promise of treating a variety of human conditions such as diabetes, cancer, and neurological diseases. It is thought that stem cells could be especially useful for neurological diseases and disorders as the brain has a limited capacity for self-repair and regeneration. Additionally, there are no effective long-term treatments or cures for certain brain disorders or neurodegenerative diseases such as Alzheimers, Parkinsons, and Huntingtons disease. Collectively, these conditions represent a significant unmet medical need. Regenerative approaches for the brain have the potential to address the cause of the disease, rather than simply addressing symptoms, by repairing or reversing the disease state. However, because the underlying causes of the brain diseases are diverse, several different approaches are required to adequately address the various causes. Some examples include cell replacement for dead or lost cells, modification and augmentation of faulty circuitry, and delivery of therapeutics to poorly functioning cells for protection from degeneration. While some cell types and sources have been identified (e.g. fetal porcine ganglionic eminence cells and dopaminergic neurons), their efficacy has not been proven. In addition, questions remain about whether such cells will form brain tumors in vivo, persist for long periods of time, or will work in aged brains, when people are most susceptible to neurological disease. There is a need in the field for the identification of cell types that can be applied in many disease contexts. DESCRIPTION: UCSF Researchers have discovered that a population of neural precursors, called medial ganglionic eminence (MGE cells), possess several advantageous properties that would make them useful for a number of neurological diseases. When injected into various regions of the brain, MGE cells disperse homogenously over long distances, form inhibitory interneurons (GABAergic neurons), integrate to form functional connections with endogenous circuits, and influence the activity of surrounding neurons. Interestingly, MGE cells behave this way in postnatal brains, suggesting they could work in aged brains. By virtue of these qualities, it is thought that MGE cells can be used to treat several brain diseases via cell replacement, modification of endogenous circuitry, or by delivery of therapeutics. To support this assertion, the researchers have performed proof-of-principle experiments in rodent models of epilepsy and Parkinsons disease. Implantation of MGE cells into the cortex of postnatal brains in rodent models of epilepsy was shown to significantly reduce seizure symptoms. MGE cells achieved this via both GABAergic modulation of electrical activity and cellular replacement of inhibitory neurons. Further, implantation of MGE cells into the striatum of 6-OHDA rodents was shown to ameliorate symptoms of Parkinsons disease via modulation of faulty circuitry resulting from degeneration of dopaminergic input. Based on these initial data, the researchers envision that MGE cells could be applied to additional brain disorders. Indeed, preliminary data suggest that MGE cells could be used to treat diseases caused by aberrations in the organization or activity of the brain, such as stroke, cerebral palsy, and Schizophrenia. MGE cells can regulate a process known as experience-dependent plasticity, which allows for changes to be made in the wiring or activity of neurons. Selective reactivation of this process in the adult brain could result in functional reorganization that could fix or compensate for any lack of function and alleviate the symptoms of disease. Preliminary data also suggest that MGE cells can be used to treat spasticity caused by spinal cord injury. It is thought that spasticity results hyperactivity spinal circuitry. MGE cells grafted into the spinal cord are expected to integrate and produce factors that inhibit local circuitry to reduce spasticity. Experimental testing in related animal disease models is underway. (more...)

Her2/neu is over-expressed in various types of tumor cells, including 20-30% of breast cancers, adenocarcinomas of the ovary, salivary gland, stomach and kidney, colon cancer, and non-small cell lung cancer. Passive immunotherapeutics like Herceptin control and prevent further tumor cell growth. Unlike active immunotherapeutics, Herceptin does not mediate the immunological cellular destruction. Active immunotherapeutics such as vaccines elicit T helper-1 (Th1) and Cytotoxic T lymphocytes (CTL) biased immune responses and are generally observed for proteins expressed in the intracellular compartment, and less prominently with extracellular or secreted proteins. Rapid degradation of a protein containing polyepitopes can contribute to establishing a bias in the immune response, facilitate antigen presentation and, perhaps assist in establishing specificity of the immune response. This type of immunological response should result in immunological cellular destruction. (more...)

The invention is on new polymeric biomaterials. The new biomaterials were created by chemical synthesis with carbohydrates and amino acids as building blocks. The biopolymers have a specific alternating structure between carbohydrate and peptide units. (more...)

BRCA2/RAD5 1 interaction is essential for DNA repair mechanisms and play significant role in tumor resistance to irradiation and chemotherapy treatments. Effective strategies to selectively interfere with BRCA2/RAD5 1 interaction in the context of treatment and chemoprevention of neoplastic diseases are described. (more...)

Bone Morphogentic Proteins (BMP)s are involved in various developmental processes, but are most famous for the activity to stimulate bone formation. BMP signaling is one of the most extensively studied growth factor signaling pathways. This is partly because it is involved in so many different biological progresses (neurogeneisis, apoptosis, stem cell maintenance and differentiation, various organogenesis ,etc). Despite the importance, it has been rather difficult to determine the precise onset of BMP signaling during these processes and what they do in the tissues or cells where the signaling is active. A UC Irvine inventor has developed an easy reporter gene assay that can not only monitor the level of BMP signaling in vivo, but also allows isolation of the BMP responding cells. (more...)

Shoot architecture and flowering time in angiosperms depend on the balanced expression of a large number of flowering time and flower meristem identity genes. Loss-of-function mutations in the Arabidopsis EMBRYONIC FLOWER (EMF) genes cause Arabidopsis to eliminate rosette shoot growth and transform the apical meristem from indeterminate to determinate growth by producing a single terminal flower on all nodes. Alteration of EMF1 expression in transgenic plants caused progressive changes in flowering time, shoot determinacy, and inflorescence architecture. EMF1 may belong to a new class of proteins that function as transcriptional regulators of phase transition during shoot development. (more...)

Researchers at the University of California at Berkeley have identified a plant resistance gene family, the members of which encode plant resistance polypeptides having P-Loop and LRR structural motifs. This resistance gene class includes Prf, RPS2, RPM1, N, and L6 and represents a large fraction of known plant disease resistance genes. The invention further involves transgenic plants and transformed host cells that express these DNAs and exhibit enhanced disease resistance to plant pathogens. For example, when expressed in transgenic plants, Prf confers Fenthion sensitivity and resistance to a wide variety of phytopathogens, including not only Pseudomonas syringae, but also unrelated pathogens such as Xanthomonas campestris. (more...)

Scientific progress is often associated with the invention of a new experimental apparatus. New tools can increase the ease and efficiency of routine experiments as well as provide the means to make new discoveries by making possible novel experiments. The development of Lab on Chip (LOC) devices is playing an important role in the progression of many different areas of research ranging from point of care diagnostics to the search for life on Mars. LOC devices hold promise to replace existing techniques with processes that are not only more automated and consistent but also require less time and valuable reagents. Researchers at the University of California have developed an integrated LOC for cell-based studies/analysis/research. The device has integrated biological fluidic circuits with the capability of culturing cells inside of a microfluidic ?chip?, the ability to lyse the cells on demand, and the ability to perform on chip analysis of the lysate, which contains both genetic and proteinaceous material. The device is essentially a completely integrated cell-based platform capable of performing practically all of the common cell-based studies currently employed in laboratories across the world. (more...)

Plant cells are encased in cell walls that form the skeleton of plants, enabling and stabilizing growth. As the individual plant cells are separated by the cell wall and cannot directly touch, plants have evolved cytoplasmic bridges called plasmodesmata that connect the cytoplasm of adjacent cells and allow intercellular movement of large molecules. Researchers at UCB have identified a gene that modifies the plasmodesmata aperture and is modulates the movement of molecules from cell-to-cell. Control of aperture size and activity is critical for viral disease susceptibility or control since viral genomes are spread cell-to-cell through the plasmodesmata. (more...)

Minor histocompatibility (H) antigens elicit T cell responses and thereby cause chronic graft rejection and graft-vs.-host disease among MHC identical individuals. Although numerous independent H loci exist in mice of a given MHC haplotype, certain H antigens dominate the immune response and are thus of considerable conceptual and therapeutic importance. The H60 gene was isolated as a cDNA clone from the mouse strain BALB.B. This gene contains an antigenic peptide that elicits a strong cytotoxic T cell response when C57BL/6 mice are immunized with BALB.B spleen cells. References: Malarkannan et al. 1998. J Immunol. 161:3501-9. Karttunen et al. 1992. PNAS 89:6020-4. (more...)

Hidden Markov Models (HMMs) have been successfully applied to a variety of problems in molecular biology ranging from alignment problems to gene finding and annotation. Alignment problems can be solved with pair HMMs, while gene finding programs rely on generalized HMMs in order to model exon lengths. Researchers at the University of California, Berkeley have developed generalized pair HMMs, an extension of both pair and generalized HMMs. The researchers have demonstrated how generalized pair HMMs, in conjunction with approximate alignments, can be used for cross-species gene finding and can be applied to DNA-cDNA and DNA-protein alignment problems. (more...)

Apoptosis is a phenomenon observed during development of many cell types in many organisms. It is an internal, programmed cell death characterized by DNA fragmentation into nucleosome-size pieces. Anti-CD3-induced apoptosis in T-cell hybridomas and immature thymocytes requires new gene transcription and may be related to negative selection during T-cell development. Using subtractive hybridization, we isolated a complementary DNA clone encoding the orphan steroid receptor Nur77 (refs 7-9). It shows different patterns of messenger RNA induction between apoptotic and stimulated T cells. We report here the use of gel shift analysis to demonstrate that the Nur77 protein is present at high levels in apoptotic T-cell hybridomas and apoptotic thymocytes, but not in growing T cells or stimulated splenocytes. A Nur77 dominant negative protected T-cell hybridomas from activation-induced apoptosis. Hence Nur77 is necessary for induced apoptosis in T-cell hybridomas. Reference: Woronicz, J, et al., 1994 Nature 367:277-81 (more...)

Telomerase is a ribonucleoprotein (RNP) DNA polymerase that extends the ends of chromosomes in most eukaryotes. DNA synthesis by telomerase can compensate for the incomplete replication of linear chromosome ends by DNA-dependent DNA polymerases and can be required for indefinite cellular proliferation. The telomerase RNP contains a catalytically essential RNA subunit. UC Berkeley researchers have discovered functionally significant elements of the human telomerase RNA. They have demonstrated that functionally significant RNA elements can be required either for RNA stability (in vivo) or for catalytic activity (in vivo and in vitro), and discovered RNA structural requirements and RNA-protein interactions of the functionally significant RNA elements. This technology can be applied to develop screens for molecules that (a) interact with, disrupt, enhance or otherwise affect any of the functionally significant RNA elements; (b) recognize, disrupt, enhance, or otherwise affect any of the functionally significant RNA protein interactions; and (c) disrupt, enhance, or otherwise affect the catalytic activity of telomerase reconstituted with functionally significant RNA elements, including the use of differentially reconstituted telomerases as tests of specificity. In addition, this technology can be applied to (d) affect telomerase activity in vivo or in vitro; and (e) further characterize the functionally significant elements of human telomerase. (more...)

Hollick, Jay B.; Chandler, Vicki L. Genetic factors required to maintain repression of a paramutagenic maize pl1 allele. Genetics. January, 2001. 157(1):369-378. Abstract: A genetic screen identified two novel gene functions required to maintain mitotically and meiotically heritable gene silencing associated with paramutation of the maize purple plant 1 (pl1) locus. Paramutation at pl1 leads to heritable alterations of pl1 gene regulation; the Pl-Rhoades (Pl-Rh) allele, which typically confers strong pigmentation to juvenile and adult plant structures, changes to a lower expression state termed Pl'-mahogany (Pl'). Paramutation spontaneously occurs at low frequencies in Pl-Rh homozygotes but always occurs when Pl-Rh is heterozygous with Pl'. We identified four mutations that caused increased Pl' pigment levels. Allelism tests revealed that three mutations identified two new maize loci, required to maintain repression 1 (rmr1) and rmr2 and that the other mutation represents a new allele of the previously described mediator of paramutation 1 (mop1) locus. RNA levels from Pl' are elevated in rmr mutants and genetic tests demonstrate that Pl' can heritably change back to Pl-Rh in rmr mutant individuals at variable frequencies. Pigment levels controlled by two pl1 alleles that do not participate in paramutation are unaffected rmr mutants. These results suggest that RMR functions are intimately involved in maintaining the repressed expression state of paramutant Pl' alleles. Despite strong effects on Pl' repression, rmr mutant plants have no gross developmental abnormalities even after several generations of inbreeding, implying that RMR1 and RMR2 functions are not generally required for developmental homeostasis. also see: Dorweiler, Jane E.; Carey, Charles C.; Kubo, Kenneth M.; Hollick, Jay B.; Kermicle, Jerry L.; Chandler, Vicki L. mediator of paramutation1 is required for establishment and maintenance of paramutation at multiple maize loci. Plant Cell. November, 2000. 12(11):2101-2118. Abstract: Paramutation is the directed, heritable alteration of the expression of one allele when heterozygous with another allele. Here, the isolation and characterization of a mutation affecting paramutation, mediator of paramutation1-1 (mop1-1), are described. Experiments demonstrate that the wild-type gene Mop1 is required for establishment and maintenance of the paramutant state. The mop1-1 mutation affects paramutation at the multiple loci tested but has no effect on alleles that do not participate in paramutation. The mutation does not alter the amounts of actin and ubiquitin transcripts, which suggests that the mop1 gene does not encode a global repressor. Maize plants homozygous for mop1-1 can have pleiotropic developmental defects, suggesting that mop1-1 may affect more genes than just the known paramutant ones. The mop1-1 mutation does not alter the extent of DNA methylation in rDNA and centromeric repeats. The observation that mop1 affects paramutation at multiple loci, despite major differences between these loci in their gene structure, correlations with DNA methylation, and stability of the paramutant state, suggests that a common mechanism underlies paramutation. A protein-based epigenetic model for paramutation is discussed. (more...)