Dopamine D-3 receptors regulate GABA(A) receptor function through a phospho-dependent endocytosis mechanism in nucleus accumbens

The dopamine D-3 receptor, which is highly enriched in nucleus accumbens (NAc), has been suggested to play an important role in reinforcement and reward. To understand the potential cellular mechanism underlying D-3 receptor functions, we examined the effect of D-3 receptor activation on GABA(A) receptor (GABA(A)R)-mediated current and inhibitory synaptic transmission in medium spiny neurons of NAc. Application of PD128907 [(4aR, 10bR)-3,4a, 4,10b-tetrahydro-4-propyl-2H, 5H-[1] benzopyrano-[4,3-b]-1,4-oxazin-9-ol hydrochloride], a specific D-3 receptor agonist, caused a significant reduction of GABAAR current in acutely dissociated NAc neurons and miniature IPSC amplitude in NAc slices. This effect was blocked by dialysis with a dynamin inhibitory peptide, which prevents the clathrin/activator protein 2 (AP2)-mediated GABA(A) receptor endocytosis. In addition, the D-3 effect on GABA(A)R current was prevented by agents that manipulate protein kinase A (PKA) activity. Infusion of a peptide derived from GABA(A) beta subunits, which contains an atypical binding motif for the clathrin AP2 adaptor complex and the major PKA phosphorylation sites and binds with high affinity to AP2 only when dephosphorylated, diminished the D-3 regulation of IPSC amplitude. The phosphorylated equivalent of the peptide was without effect. Moreover, PD128907 increased GABAAR internalization and reduced the surface expression of GABA(A) receptor beta subunits in NAc slices, which was prevented by dynamin inhibitory peptide or cAMP treatment. Together, our results suggest that D-3 receptor activation suppresses the efficacy of inhibitory synaptic transmission in NAc by increasing the phospho-dependent endocytosis of GABA(A) receptors

Predicting the state of charge and health of batteries using data-driven machine learning

Machine learning is a specific application of artificial intelligence that allows computers to learn and improve from data and experience via sets of algorithms, without the need for reprogramming. In the field of energy storage, machine learning has recently emerged as a promising modelling approach to determine the state of charge, state of health and remaining useful life of batteries. First, we review the two most studied types of battery models in the literature for battery state prediction: the equivalent circuit and physics-based models. Based on the current limitations of these models, we showcase the promise of various machine learning techniques for fast and accurate battery state prediction. Finally, we highlight the major challenges involved, especially in accurate modelling over length and time, performing in situ calculations and high-throughput data generation. Overall, this work provides insights into real-time, explainable machine learning for battery production, management and optimization in the future

DEA model for measuring input-and-output-based technical efficiency

2001-2002 > Academic research: refereed > Publication in refereed journalVersion of RecordPublishe

DEA for measuring technical efficiency associated with slacks

2001-2002 > Academic research: refereed > Publication in refereed journalVersion of RecordPublishe

Up-regulation of METCAM/MUC18 promotes motility, invasion, and tumorigenesis of human breast cancer cells

<p>Abstract</p> <p>Background</p> <p>Conflicting research has identified METCAM/MUC18, an integral membrane cell adhesion molecule (CAM) in the Ig-like gene super-family, as both a tumor promoter and a tumor suppressor in the development of breast cancer. To resolve this, we have re-investigated the role of this CAM in the progression of human breast cancer cells.</p> <p>Methods</p> <p>Three breast cancer cell lines were used for the tests: one luminal-like breast cancer cell line, MCF7, which did not express any METCAM/MUC18, and two basal-like breast cancer cell lines, MDA-MB-231 and MDA-MB-468, which expressed moderate levels of the protein.</p> <p>MCF7 cells were transfected with the human METCAM/MUC18 cDNA to obtain G418-resistant clones which expressed the protein and were used for testing effects of human METCAM/MUC18 expression on <it>in vitro </it>motility and invasiveness, and <it>in vitro </it>and <it>in vivo </it>tumorigenesis. Both MDA-MB-231 and MDA-MB-468 cells already expressed METCAM/MUC18. They were directly used for <it>in vitro </it>tests in the presence and absence of an anti-METCAM/MUC18 antibody.</p> <p>Results</p> <p>In MCF7 cells, enforced METCAM/MUC18 expression increased <it>in vitro </it>motility, invasiveness, anchorage-independent colony formation (<it>in vitro </it>tumorigenesis), and <it>in vivo </it>tumorigenesis. In both MDA-MB-231 and MDA-MB-468 cells, the anti-METCAM/MUC18 antibody inhibited both motility and invasiveness. Though both MDA-MB-231 and MDA-MB-468 cells established a disorganized growth in 3D basement membrane culture assay, the introduction of the anti-METCAM/MUC18 antibody completely destroyed their growth in the 3D culture.</p> <p>Conclusion</p> <p>These findings support the notion that human METCAM/MUC18 expression promotes the progression of human breast cancer cells by increasing their motility, invasiveness and tumorigenesis.</p

EGFR Gene Overexpression Retained in an Invasive Xenograft Model by Solid Orthotopic Transplantation of Human Glioblastoma Multiforme Into Nude Mice

Orthotopic xenograft animal model from human glioblastoma multiforme (GBM) cell lines often do not recapitulate an extremely important aspect of invasive growth and epidermal growth factor receptor (EGFR) gene overexpression of human GBM. We developed an orthotopic xenograft model by solid transplantation of human GBM into the brain of nude mouse. The orthotopic xenografts sharing the same histopathological features with their original human GBMs were highly invasive and retained the overexpression of EGFR gene. The murine orthotopic GBM models constitute a valuable in vivo system for preclinical studies to test novel therapies for human GBM

Insights from Amphioxus into the Evolution of Vertebrate Cartilage

Central to the story of vertebrate evolution is the origin of the vertebrate head, a problem difficult to approach using paleontology and comparative morphology due to a lack of unambiguous intermediate forms. Embryologically, much of the vertebrate head is derived from two ectodermal tissues, the neural crest and cranial placodes. Recent work in protochordates suggests the first chordates possessed migratory neural tube cells with some features of neural crest cells. However, it is unclear how and when these cells acquired the ability to form cellular cartilage, a cell type unique to vertebrates. It has been variously proposed that the neural crest acquired chondrogenic ability by recruiting proto-chondrogenic gene programs deployed in the neural tube, pharynx, and notochord. To test these hypotheses we examined the expression of 11 amphioxus orthologs of genes involved in neural crest chondrogenesis. Consistent with cellular cartilage as a vertebrate novelty, we find that no single amphioxus tissue co-expresses all or most of these genes. However, most are variously co-expressed in mesodermal derivatives. Our results suggest that neural crest-derived cartilage evolved by serial cooption of genes which functioned primitively in mesoderm

Benign Orbital Tumors with Bone Destruction in Children

Purpose: To present rare benign orbital tumors with bone destruction in children who could not be diagnosed presurgically and may simulate malignant ones. Methods: A retrospective review of cases. Clinical, operative and pathological records in all children with a diagnosis of benign orbital tumors who showed remarkable bone destruction at a tertiary Ophthalmic Center in China between Jan 1, 2000 and Dec 31, 2009 were reviewed. All patients had definitive histopathologic diagnosis. Results: Eight patients with benign orbital tumors showed obvious bone destruction, including six cases of eosinophilic granuloma, one case of leiomyoma and one case of primary orbital intraosseous hemangioma. Among them, three patients were females and five patients were males. Tumors were unilateral in all cases, with both the right and left side affected equally. Age ranged from 3 to 7 years (mean 4.1 years). Symptom duration ranged from 1 to 5 weeks (mean 4.8 weeks). Eyelid swelling and palpable mass were the most common complaint. There was no evidence for multifocal involvement in cases with eosinophilic granuloma. Among six patients with eosinophilic granuloma, two were treated with low dose radiation (10 Gy), three received systemic corticosteroid and one was periodically observed only after incisional biopsy or subtotal curettage. There was no postoperative therapeutic intervention in the two patients with leiomyoma and intraosseous hemangioma. All eight patients regained normal vision without local recurrence after a mean follow-up time o