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Here we describe an important involvement of Cdk5/p35 in regulating the gene expression of acetylcholine receptor (AChR) at the neuromuscular synapse. Cdk5 and p35 were prominently expressed in embryonic muscle, and concentrated at the neuromuscular junction in adulthood. Neuregulin increased the p35-associated Cdk5 kinase activity in the membrane fraction(More)
The participation of ephrins and Eph receptors in guiding motor axons during muscle innervation has been well documented, but little is known about their expression and functional significance in muscle at later developmental stages. Our present study investigates the expression and localization of Eph receptors and ephrins in skeletal muscle. Prominent(More)
Neurotrophic factors are target-derived proteins that promote the survival and differentiation of the innervating neurons. Increasing evidence indicate the involvement of these factors and receptors during the formation and maturation of the neuromuscular junction. To gain further insight on the expression pattern of these factors and receptors in(More)
Polymorphisms at positions -491, -427 and -219 in the promoter region of the Apolipoprotein E APOE gene have been variously reported to confer an increased risk of developing Alzheimer's disease (AD) independent of the effect of epsilon 2, 3 or 4 alleles in exon 4. In order to assess APOE promoter polymorphisms as independent risk factors in AD we have(More)
Muscle-specific kinase (MuSK) is part of the receptor complex that is involved in the agrin-induced formation of the neuromuscular junction. In the rodent, prominent mRNA expression of MuSK is restricted to skeletal muscle while the expression of agrin can also be detected in brain and certain nonneuronal tissues. The recent identification of Xenopus MuSK(More)
Muscle specific kinase (MuSK) mediates agrin-induced acetylcholine receptor (AChR) aggregation on muscle membrane at the neuromuscular junction (NMJ). To examine whether MuSK enhances NMJ formation during embryonic development in vivo, the level of expression of MuSK was manipulated in Xenopus embryos and the functional consequence at the NMJ was assessed.(More)
Pharmacological inhibition of the MAPK pathway with MEK or BRAF antagonists has proved successful in inducing regression of melanoma tumors bearing the targeted activating mutations. Moreover, antibodies targeting T-cell immune checkpoint inhibitors CTLA-4 or PD-L1/PD-1 have demonstrated the capacity to generate durable responses in patients with multiple(More)
  • A Gruber, Ahagon, +25 authors D J Gapped
  • 2003
DNA reads generated by large-scale sequencing projects have to be processed before further analyses in order to perform vector/primer masking, low-quality trimming and contaminant removal. This sequential processing involves several steps and the use of different computer programs, each one following its own calling convention and input/output formats. As a(More)
Expression of PD-L1, the ligand for T-cell inhibitory receptor PD-1, is one key immunosuppressive mechanism by which cancer avoids eradication by the immune system. Therapeutic use of blocking antibodies to PD-L1 or its receptor PD-1 has produced unparalleled, durable clinical responses, with highest likelihood of response seen in patients whose tumour or(More)
Programmed cell death-1 (PD-1) is a coinhibitory receptor that suppresses T cell activation and is an important cancer immunotherapy target. Upon activation by its ligand PD-L1, PD-1 is thought to suppress signaling through the T cell receptor (TCR). By titrating PD-1 signaling in a biochemical reconstitution system, we demonstrate that the co-receptor CD28(More)
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