Long-term memory is formed by alterations in glutamate-dependent excitatory synaptic transmission, which is in turn regulated by synaptosomal protein of 25 kDa (SNAP-25), a key component of the soluble N-ethylmaleimide-sensitive factor attachment protein receptor complex essential for exocytosis of neurotransmitter-filled synaptic vesicles. Both reduced and excessive SNAP-25 activity has been ...

The present invention is directed to a method of transducing mammalian cochlear cells, more preferably, cochlear hair cells and support cells. The method involves the delivery of adeno-associated virus (AAV) to a target mammalian cochlear cell. The AAV co...

The tissue kallikrein�kinin system is important in regulating cardiovascular and renal function, and dysregulation of the system has been implicated in heart and kidney pathologies. These findings suggest that if balance can be restored to the kallikrein-kinin axis, then associated disease progression may be attenuated. To test this hypothesis, recombinant adeno-associated virus ...

The ability of transient immunosuppression with a combination of a non-depleting anti-CD4 (NDCD4) antibody and cyclosporine (CyA) to abrogate immune reactivity to both adeno-associated viral vector (AAV) and its transgene product was evaluated. This combination of immunosuppressants resulted in a 20-fold reduction in the resulting anti-AAV8 antibody titres, to levels in na�ve mice, following ...

of Medicine, The University of Iowa, Iowa City, IA, USA and 4 Center for Gene Therapy of Cystic Fibrosis- associated virus (rAAV)-mediated gene therapies to the lung for cystic fibrosis (CF). As new ferret and pig Keywords: AAV; species; tropism; sialic acid; lung; cystic fibrosis Recombinant adeno-associated virus (r

to late-onset obesity, including leptin resistance [29], the role of dopaminergic neurons has not been- cially effective in reducing obesity when other agents have failed such as in the leptin resistant aged injection. Brain Res 1997;747:92�102. [20] Li H, Matheny M, Nicolson M, T�umer N, Scarpace PJ. Leptin gene

Apart from its role in axon guidance, netrin-1 is also known to be pro-angiogenic. The aim of this study is to determine whether adeno-associated viral (AAV) mediated overexpression of netrin-1 improves post-stroke neurovascular structure and recovery of function. AAV-Netrin-1 or AAV-LacZ of 1�10(10) genome copies each was injected medial and posterior ...

Muscular dystrophies are diseases characterized by muscle weakness together with cycles of degeneration and regeneration of muscle fibres, resulting in a progressive decrease of muscle mass, diminished muscle force generation and an increase in fibrosis. Fibrotic disorders are the endpoint of many chronic diseases in different tissues, where accumulation of the extracellular ...

Original reports of adeno-associated virus (AAV) vector-mediated gene transfer to the muscle resulted in high-level ?-galactosidase (?-gal) expression and the promise of a viral vector that was largely nonimmunogenic. Subsequent attempts to utilize these vectors for genetic vaccination, however, demonstrated that it was possible to activate cellular and humoral immunity to AAV-encoded antigens. ...

In the present study we demonstrate that adeno-associated virus (AAV)-mediated anti-DR5 (death receptor 5) mouse-human chimeric antibody (shorten as Adximab) expression significantly suppressed tumor cell growth by inducing apoptosis both in vitro and in vivo. The viral-expressed and cell-secreted Adximab efficiently bound DR5 with an affinity of 0.7nM and induced apoptosis of ...

Exposure to particulate matter (PM2.5-10), including diesel exhaust particles (DEP) has been reported to induce lung injury and exacerbation of asthma and chronic obstructive pulmonary disease. Alveolar macrophages play a major role in the lung's response to inhaled particles and...

Progression in R6/1 Huntington's Disease Transgenic Mice Edgardo Rodriguez-Lebron,1,* Eileen M. Denovan://users.mbi.ufl.edu/mandel/mandel.html. Available online 12 July 2005 Huntington's disease (HD) is a fatal neurodegenerative disorder caused, transcriptional dysregulation, polyglutamine, neuronal intranuclear inclusions INTRODUCTION HuntingtonTs disease

BackgroundMore than 90% of Duchenne muscular dystrophy (DMD) patients develop cardiomyopathy, and many die of cardiac failure. Despite tremendous progress in skeletal muscle gene therapy, few attempts have been made to treat cardiomyopathy. Microdystrophin genes are shown to correct skeletal muscle pathological lesions in the mdx mouse model for DMD. Here, we tested the therapeutic potential of ...

Recent success in clinical trials supports the use of adeno-associated viral (AAV) vectors for gene therapy of retinal diseases caused by defects in the retinal pigment epithelium (RPE). In contrast, evidence of the efficacy of AAV-mediated gene transfer to retinal photoreceptors, the major site of inherited retinal diseases, is less robust. In addition, although AAV-mediated ...

Recent success in clinical trials supports the use of adeno-associated viral (AAV) vectors for gene therapy of retinal diseases caused by defects in the retinal pigment epithelium (RPE). In contrast, evidence of the efficacy of AAV-mediated gene transfer to retinal photoreceptors, the major site of inherited retinal diseases, is less robust. In addition, although AAV-mediated ...

Oxidative damage in the dopaminergic neurons of substantia nigra pars compacta (SNpc) plays an important role in the pathogenesis of Parkinson's disease (PD). Heat shock proteins 70 kDa (HSP70s) are a sub-family of molecular chaperones involved in not only protein folding and degradation but also antioxidant defense and anti-apoptotic pathways. Here, a transgenic mice ...

Imatinib is a chemotherapeutic drug used for the treatment of chronic myeloid leukemia (CML). Recent data showed imatinib-induced cell death in various types of cancers. Autophagy is the physiological process in which cellular components are broken down by the lysosomal activation. In this study, we aimed to examine the effects of imatinib on autophagy in addition to apoptosis ...

ObjectivesMutations in the gene encoding for pancreatic secretory trypsin inhibitor (PSTI) can contribute to chronic pancreatitis. In the current study, we tested whether over-expression of pancreatic secretory trypsin inhibitor-I in mice protects against chronic pancreatitis and pancreatic fibrosis.MethodsRat PSTI-I expression was ...

Activation of the transcription factor Nrf2 in astrocytes coordinates the up-regulation of antioxidant defenses and confers protection to neighboring neurons. Dominant mutations in Cu/Zn-superoxide dismutase (SOD1) cause familial forms of amyotrophic lateral sclerosis (ALS), a fatal disorder characterized by the progressive loss of motor neurons. Non-neuronal cells, including astrocytes, shape ...

J. Neurochem. (2011) 118, 1101-1112. ABSTRACT: To characterize the long-term effects of adolescent marijuana abuse, we performed a proteomic analysis of cerebellar extracts from adult female rats with and without ovariectomy that were treated with ?9-THC for 40?days during adolescence. Six proteins were found to significantly differ among the four treatment groups, with ?9-THC and ovariectomy ...

Chronic hepatitis C virus (HCV) infection is associated with cirrhosis, autoimmunity and lymphoproliferative disorders. We have previously reported a differential regulation of T and B lymphocytes by HCV core protein in vitro. In this report, we employed a translational approach to characterize the activation status of peripheral B cells from individuals with ...

Regular endurance exercise remodels skeletal muscle, largely through the peroxisome proliferator-activated receptor ? coactivator 1? (PGC-1?). PGC-1? promotes fiber-type switching and resistance to fatigue. Intracellular calcium levels might play a role in both adaptive phenomena, yet a role for PGC-1? in the adaptation of calcium handling in skeletal muscle remains unknown. Using mice with ...

Gene expression profiling (GEP) of 8 stage 0/I untreated Chronic Lymphocytic Leukemia (CLL) patients showed over-expression of Frizzled 3 (FZD3)/ROR-1 receptor tyrosine kinase (RTK), FLT-3 RTK and CXCR3 G-protein coupled receptor (GPCR). RT-PCR of 24 genes in 21 patients of the WNT pathway corroborated the GEP. Transforming growth factor?, fibromodulin, ...

BackgroundAdeno-associated virus-2 (AAV-2)-mediated gene therapy is quite suitable for local or regional application in head and neck cancer squamous cell carcinoma (HNSCC). However, its low transduction efficiency has limited its further development as a therapeutic agent. DNA damaging agents have been shown to enhance AAV-mediated transgene expression. Cisplatin, one of the ...

Tibia fracture in rats initiates a syndrome resembling the complex regional pain syndrome type I. Accumulating evidence indicates that IL-1? is involved in the modulation of nociceptive information and it acts as an intermediate inflammatory mediator via up-regulation of NGF. We hypothesized that IL-1? signaling might mediate the development of the CRPS-like changes after tibial fracture, either ...

Chronic use of anabolic adrogenic steroids (AAS) has been known to cause serious adverse effects. While the effects of AASs on cardiovascular system are well known, toxicity on other organs has received less attention. A doserelated nephrotoxic effect has been proposed and a wide variety of morpho-functional damages have been observed, but the exact pathophysiological ...

Gene expression experiments were targeted in order to monitor the ABC efflux transporters, which is potentially involved in cellular detoxification/defense. Changes in expression levels of different ABC genes in kidney of Oncorhynchus mykiss fed with melamine and melamine+cyanuric acid enriched diets were recorded in both treated groups by mRNA ??(CT) relative quantification method. Expression ...

Chronic consumption of alcohol leads to liver injury. Ethanol-inducible Cytochrome P450 2E1 (CYP2E1) plays a critical role in alcohol mediated oxidative stress due to its ability to metabolize ethanol. In the present study, using the recombinant human hepatoma cell line VL-17A that over-expresses the alcohol metabolizing enzymes-alcohol dehydrogenase (ADH) and CYP2E1; and ...