TechCombo http://techcombo.com Technology, Health and News Mon, 19 Sep 2011 11:16:27 +0000 en hourly 1 http://wordpress.org/?v=3.2.1 MicroRNA-205 for the Treatment and Diagnosis of Parkinson Disease http://techcombo.com/2011/09/14/microrna-205-for-the-treatment-and-diagnosis-of-parkinson-disease-123/ http://techcombo.com/2011/09/14/microrna-205-for-the-treatment-and-diagnosis-of-parkinson-disease-123/#comments Wed, 14 Sep 2011 18:27:54 +0000 Paul Young http://techcombo.com/2011/09/14/microrna-205-for-the-treatment-and-diagnosis-of-parkinson-disease-123/
Parkinson disease (PD) is a devastating neurodegenerative movement disorder, pathologically characterized by selective loss of dopaminergic (DA) neurons in the substantia nigra pars compacta (SNpc) and the presence of intracytoplasmic inclusions named Lewy bodies and Lewy neurites (Schapira, Baillieres Clin. Neurol. 6:15-36, 1997). Increasing numbers of genes have been identified as a genetic cause of PD (Hardy et al., Ann. Neurol. 60:389-398, 2006), for example, multiple missense mutations in the leucine-rich repeat kinase 2 (LRRK2) gene were recently found to be associated with an autosomal dominant form of familial PD (Paisan-Ruiz et al., Neuron 44:595-600, 2004; Zimprich et al., Neuron 44:601-607, 2004; Zabetian et al., Neurology 65:741-744, 2005). Recent genome-wide association studies (GWAS) also revealed LRRK2, together with SNCA (encoding alpha-syn) and PARK16, as shared risk loci for PD (Simon-Sanchez et al., Nat. Genet. 41:1308-1312, 2009; Satake et al., Nat. Genet. 41:1303-1307, 2009), indicating a potential contribution of normal LRRK2 protein to the etiology of sporadic PD cases.

Micro-RNAs (miRNAs or miRs) are evolutionarily conserved small non-protein coding transcripts that bind to partially complementary binding sites in the 3? untranslated region (3?-UTR) of target messenger RNAs (mRNAs) and control the translation of their target mRNAs at the post-transcriptional level (Bartel, Cell 116:281-297, 2004). Several miRNAs have been associated with neurodegenerative disease as well as synaptic plasticity, memory formation and developmental cell fate decisions in the nervous system (Hebert and De Strooper, Trends Neurosci. 32:199-206, 2009; Kosik, Nat. Rev. Neurosci. 7:911-920, 2006).

NIH inventors have recently discovered that LRRK2 protein expression is significantly increased in the brain of PD patients, while expression of miR-205 is specifically down-regulated in the same patients. Also, the NIH inventors have discovered that the expression levels of LRRK2 and miR-205 are dynamically regulated and reversely correlated in multiple brain regions and at different ages in mouse brains, indicating that miR-205 plays a regulatory role in LRRK2 protein expression.

Based on these novel findings, the present technology provides for novel methods of treatment of patients suffering from PD disease by modulating the amount of miR-205 in patients by administration of a miR-205 gene product, a vector encoding a miR-205 gene product or an agent that increases expression of miR-205. The present technology also provides for methods of determining the effectiveness of different candidate drugs for the treatment of PD, methods of diagnosing PD, or having an increased susceptibility to developing PD, and an in vitro process for identifying a therapeutic agent for the treatment of PD.

]]> http://techcombo.com/2011/09/14/microrna-205-for-the-treatment-and-diagnosis-of-parkinson-disease-123/feed/ 0 Novel Osteobiologic Proteins for Treatment of Osteoporosis, Rheumatoid and Neurologic Diseases http://techcombo.com/2011/09/14/novel-osteobiologic-proteins-for-treatment-of-osteoporosis-rheumatoid-and-neurologic-diseases-4-123/ http://techcombo.com/2011/09/14/novel-osteobiologic-proteins-for-treatment-of-osteoporosis-rheumatoid-and-neurologic-diseases-4-123/#comments Wed, 14 Sep 2011 18:27:53 +0000 Paul Young http://techcombo.com/2011/09/14/novel-osteobiologic-proteins-for-treatment-of-osteoporosis-rheumatoid-and-neurologic-diseases-4-123/ In an effort to find effective strategies for treatment of body tissue and structural damage as the result of trauma, cancer and other diseases, scientists at the Food and Drug Administration (FDA) have identified Cartilage-Derived Morphogenetic Proteins (CDMP) and associated pathways instrumental in replacing or regenerating damaged tissue. These proteins have unique activities likely to be useful as stand alone agents or in construction of engineered tissues.

CDMPs appear helpful in the healing of bone and joint surface lesions, and also for the repair or reconstruction of cartilaginous tissues, tendons and ligaments. The invention identifies proteins belonging to TGF-Beta superfamily that promote repair of menisci, cruciate and collateral ligaments of the knee, and rotator cuff tendons. The patent application claims nucleic acids encoding human Cartilage-Derived Morphogenetic Protein-1 (hCDMP-1) variant polypeptides. Morphogenetic proteins are able to induce the proliferation and differentiation of progenitor cells into functional bone, cartilage, tendon, or ligament tissue.

]]> http://techcombo.com/2011/09/14/novel-osteobiologic-proteins-for-treatment-of-osteoporosis-rheumatoid-and-neurologic-diseases-4-123/feed/ 0 Novel Methods for the Reversible Incorporation of Functional Groups into RNA and DNA: Synthesis and Uses for 2?-O-aminooxymethyl Nucleoside Derivatives http://techcombo.com/2011/09/14/novel-methods-for-the-reversible-incorporation-of-functional-groups-into-rna-and-dna-synthesis-and-uses-for-2-o-aminooxymethyl-nucleoside-derivatives-123/ http://techcombo.com/2011/09/14/novel-methods-for-the-reversible-incorporation-of-functional-groups-into-rna-and-dna-synthesis-and-uses-for-2-o-aminooxymethyl-nucleoside-derivatives-123/#comments Wed, 14 Sep 2011 18:27:51 +0000 Paul Young http://techcombo.com/2011/09/14/novel-methods-for-the-reversible-incorporation-of-functional-groups-into-rna-and-dna-synthesis-and-uses-for-2-o-aminooxymethyl-nucleoside-derivatives-123/ The delivery of DNA/RNA therapeutic drugs is still a major hurdle for the clinical application of DNA/RNA-based drugs. Also, developments in silencing the expression of specific genes, through RNA interference pathways, have led to an increased demand for synthetic RNA sequences and have created a pressing need for rapid and efficient methods for RNA synthesis. Recently, FDA scientists have developed a novel phosphoramidite, 2?-O-aminooxymethyl ribonucleoside (2?-O-protected compounds). The 2?-O-aminooxymethyl ribonucleoside can be modified with any type of functional group using an oximation reaction as long as the functional group contains an aldehyde, ketone, or acetal group. Modification of the 2?-O-aminooxymethyl with an aldehyde results in a conjugated 2?-phosphoramidite that could be readily converted back to the native ribonucleoside and its corresponding by-product. On the other hand, the oximation of 2?-O-aminooxymethy with a ketone results in an irreversible conjugated form of the phosphoramidite.

The 2?-O-protected compounds of the present technology have several advantages, for example, the 2?-O-protected compound is stable during the various reaction steps involved in oligonucleotide synthesis; and the protecting group can be easily removed after the synthesis of the oligonucleotide, for example, by reaction with tetrabutylammonium fluoride; and the O-protected groups do not generate DNA/RNA alkylating side products, which have been reported during removal of 2?-O-(2-cyanoethyl)oxymethyl or 2?-O-[2-(4-tolylsulfonyl)ethoxymethyl groups under similar conditions.

]]> http://techcombo.com/2011/09/14/novel-methods-for-the-reversible-incorporation-of-functional-groups-into-rna-and-dna-synthesis-and-uses-for-2-o-aminooxymethyl-nucleoside-derivatives-123/feed/ 0 The Human Nuclear Co-Repressor Gene: Applications for Cancer Diagnostics/Therapeutics and Gene Expression Research http://techcombo.com/2011/09/14/the-human-nuclear-co-repressor-gene-applications-for-cancer-diagnosticstherapeutics-and-gene-expression-research-123/ http://techcombo.com/2011/09/14/the-human-nuclear-co-repressor-gene-applications-for-cancer-diagnosticstherapeutics-and-gene-expression-research-123/#comments Wed, 14 Sep 2011 18:27:49 +0000 Paul Young http://techcombo.com/2011/09/14/the-human-nuclear-co-repressor-gene-applications-for-cancer-diagnosticstherapeutics-and-gene-expression-research-123/ The human nuclear receptor co-repressor (huN-CoR) forms multimolecular complexes that alters chromatin structure, resulting in disrupted gene expression. The huN-CoR complex is central to normal processes such as erythropoiesis and thymocyte development, but is also linked to multiple cancers including colorectal carcinomas, endometrial cancers and leukemia, particularly acute myeloid leukemia. Thus, huN-CoR is a potentially-valuable tool for cancer diagnosis, as well as a target for the development of huN-CoR-based cancer therapeutics. HuN-CoR is also an attractive research tool for the study of gene regulation, epigenetic modification and gene silencing.

The technology claims nucleic acid sequences comprising the huN-CoR gene and fragments thereof, as well as a gene chip array incorporating such fragments.

]]> http://techcombo.com/2011/09/14/the-human-nuclear-co-repressor-gene-applications-for-cancer-diagnosticstherapeutics-and-gene-expression-research-123/feed/ 0 Production of Adeno-Associated Viruses in Insect Cells http://techcombo.com/2011/09/14/production-of-adeno-associated-viruses-in-insect-cells-123/ http://techcombo.com/2011/09/14/production-of-adeno-associated-viruses-in-insect-cells-123/#comments Wed, 14 Sep 2011 18:27:47 +0000 Paul Young http://techcombo.com/2011/09/14/production-of-adeno-associated-viruses-in-insect-cells-123/ Adeno-associated virus (AAV) is being developed for gene therapy applications. This virus type presents several advantages over alternate vectors for therapeutic gene delivery. AAV is not considered pathogenic and transduces stably dividing and non-dividing cells. AAV also shows good serotype specificity to various cell types for targeted gene delivery.

The present invention describes a highly scalable adeno-associated virus (AAV) vector production method in insect cells. The system for producing recombinant AAV (rAAV) uses the AAV Rep protein and an AAV ITR. This production method produces virus particles much more efficiently than the standard mammalian cell culture system. Yields of rAAV produced in Sf9 cells exceed 10e15 per liter for some constructs. The improvement in production efficiency translates into lower production costs and potential for commercial scale manufacturing. In addition, all serotypes of AAV can be produced, with the respective AAV serotype vectors available for the immediate scale up of AAV production.

This technology will give a company producing large quantities of AAV a significant competitive advantage over traditional AAV production methods.

]]> http://techcombo.com/2011/09/14/production-of-adeno-associated-viruses-in-insect-cells-123/feed/ 0 Modulation of Leucine-rich Repeats and Calponin Homology Domain-containing Protein 4 (Lrch4) Activity for Therapeutic Applications http://techcombo.com/2011/09/14/modulation-of-leucine-rich-repeats-and-calponin-homology-domain-containing-protein-4-lrch4-activity-for-therapeutic-applications-123/ http://techcombo.com/2011/09/14/modulation-of-leucine-rich-repeats-and-calponin-homology-domain-containing-protein-4-lrch4-activity-for-therapeutic-applications-123/#comments Wed, 14 Sep 2011 18:27:46 +0000 Paul Young http://techcombo.com/2011/09/14/modulation-of-leucine-rich-repeats-and-calponin-homology-domain-containing-protein-4-lrch4-activity-for-therapeutic-applications-123/ NIH Inventors have recently discovered a novel Leucine-rich repeat and calponin homology domain-containing protein 4 (Lrch4) in a proteomic screen of the plasma membrane of lipopolysaccharide (LPS)-exposed macrophages. Expression data by RT-PCR revealed that all Lrch family members (1-4) are expressed in macrophages, but only Lrch4 was recruited into lipid rafts (signaling microdomains of the plasma membrane) by LPS. Lrch4 is the most highly expressed Lrch family member in mouse tissues. It is a predicted single-spanning transmembrane protein that is encoded by the Lrch4 gene in humans. The Lrch4 ectodomain is predicted to have a series of leucine-rich repeats, the motifs by which Toll like Receptors (TLR) are thought to bind microbial ligands. The human form of Lrch4 is 83% identical to murine Lrch4 and is predicted to have 680 amino acids and a molecular weight of 73 kDa.

NIH inventors have shown that Lrch4 is expressed on the plasma membrane of macrophages. They have determined that Lrch4 regulates pro-inflammatory signals (NF-kappaB activation, cytokine induction) emanating from all TLRs tested, and also regulates ligand-independent signals from MyD88. Further, LPS-induced p38, JNK, and NFkappaB activation are attenuated following Lrch4 knockdown, indicating that Lrch4 regulates upstream LPS signaling events. LPS-induced expression of the NF-kappaB-dependent cytokine TNFalpha was attenuated following Lrch4 knockdown at the level of both transcript and protein. Based on these and other findings, the inventors of this technology propose that Lrch4 may be a novel component of TLR receptor complexes and that modulation of Lrch4 activity might open up new opportunities for developing novel therapeutics for inflammatory diseases.

]]> http://techcombo.com/2011/09/14/modulation-of-leucine-rich-repeats-and-calponin-homology-domain-containing-protein-4-lrch4-activity-for-therapeutic-applications-123/feed/ 0 Identification of EGFR as A Receptor for AAV6 Transduction http://techcombo.com/2011/09/14/identification-of-egfr-as-a-receptor-for-aav6-transduction-123/ http://techcombo.com/2011/09/14/identification-of-egfr-as-a-receptor-for-aav6-transduction-123/#comments Wed, 14 Sep 2011 18:27:43 +0000 Paul Young http://techcombo.com/2011/09/14/identification-of-egfr-as-a-receptor-for-aav6-transduction-123/ AAV vectors offer unique advantages in gene therapy applications. Studies have shown that these replication deficient parvovirus vectors can deliver DNA to specific tissues and confer long-term transgene expression in a variety of systems. Although many studies have looked at the tissue-specific expression elicited by each of the AAV serotypes, a true understanding of how AAV transduces these tissues is still unclear. Of the large AAV family, only a few receptors or co-receptors have been identified. The ability to better target transduction to specific tissues on the basis of the receptors that each serotype uses for entry is essential for selecting a serotype given the receptor expression in specific tissue, or to exploit altered receptor expression under disease conditions.

AAV6 has been reported to effectively transduce muscle, lung, brain, and multiple types of tumors, including gliomas and lung adenocarcinomas. By using a bioinformatics based screen approach, the NIH investigators discovered that the epidermal growth factor receptor (EGFR) is a co-receptor for AAV6 infection in mammalian cells, and is necessary for efficient vector internalization.

]]> http://techcombo.com/2011/09/14/identification-of-egfr-as-a-receptor-for-aav6-transduction-123/feed/ 0 NIH-Funded Researchers Discover Genetic Link to Mesothelioma http://techcombo.com/2011/09/14/nih-funded-researchers-discover-genetic-link-to-mesothelioma-123/ http://techcombo.com/2011/09/14/nih-funded-researchers-discover-genetic-link-to-mesothelioma-123/#comments Wed, 14 Sep 2011 07:12:12 +0000 Jack Tanston http://techcombo.com/2011/09/14/nih-funded-researchers-discover-genetic-link-to-mesothelioma-123/ Scientists have found that individuals who carry a mutation in a gene called BAP1 are susceptible to developing two forms of cancer — mesothelioma, and melanoma of the eye. Additionally, when these individuals are exposed to asbestos or similar mineral fibers, their risk of developing mesothelioma, an aggressive cancer of the lining of the chest and abdomen, may be markedly increased.

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]]> http://techcombo.com/2011/09/14/nih-funded-researchers-discover-genetic-link-to-mesothelioma-123/feed/ 0 Media Advisory for Raleigh/Durham, North Carolina http://techcombo.com/2011/09/14/media-advisory-for-raleighdurham-north-carolina-123/ http://techcombo.com/2011/09/14/media-advisory-for-raleighdurham-north-carolina-123/#comments Wed, 14 Sep 2011 07:12:10 +0000 Jack Tanston http://techcombo.com/2011/09/14/media-advisory-for-raleighdurham-north-carolina-123/ Members of the local media are invited to attend a press availability followed by a roundtable discussion on the multiple benefits of federally-funded research. Join local researchers as they discuss how funding from federal agencies is allowing them to do cutting-edge science and medical research that is benefiting the citizens of North Carolina and the nation. Rose Hoban, former health reporter at North Carolina Public Radio and founder of NC Health News, will preside over a panel discussion, which will include Congressman David Price; Linda Birnbaum, Ph.D., director of the leading NIH institute supporting environmental health research; and local researchers, as they provide examples of health studies being supported in North Carolina’s Research Triangle Park.

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]]> http://techcombo.com/2011/09/14/media-advisory-for-raleighdurham-north-carolina-123/feed/ 0 Exercise May Help Prevent Brain Damage Caused by Alzheimer’s Disease http://techcombo.com/2011/09/14/exercise-may-help-prevent-brain-damage-caused-by-alzheimers-disease-123/ http://techcombo.com/2011/09/14/exercise-may-help-prevent-brain-damage-caused-by-alzheimers-disease-123/#comments Wed, 14 Sep 2011 07:12:09 +0000 Jack Tanston http://techcombo.com/2011/09/14/exercise-may-help-prevent-brain-damage-caused-by-alzheimers-disease-123/ Regular exercise could help prevent brain damage associated with neurodegenerative diseases like Alzheimer’s, according to research published this month in Elsevier’s journal Brain, Behavior, and Immunity.

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Nearly two years after the Deepwater Horizon oil spill in the Gulf of Mexico, some workers have questions about their health as a result of participating in the cleanup. More than 18,000 cleanup workers and volunteers have enrolled in the Gulf Long-term Follow-up Study (GuLF STUDY), a national effort to determine whether the oil spill contributed to physical or mental health problems. It is alread…
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