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- Juneja, M, et al.
(författare)
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PFN2 and GAMT as common molecular determinants of axonal Charcot-Marie-Tooth disease
- 2018
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Ingår i: Journal of neurology, neurosurgery, and psychiatry. - : BMJ. - 1468-330X .- 0022-3050. ; 89:8, s. 870-878
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Tidskriftsartikel (refereegranskat)abstract
- Charcot-Marie-Tooth type 2 (CMT2) neuropathy is characterised by a vast clinical and genetic heterogeneity complicating its diagnosis and therapeutic intervention. Identification of molecular signatures that are common to multiple CMT2 subtypes can aid in developing therapeutic strategies and measuring disease outcomes.MethodsA proteomics-based approach was performed on lymphoblasts from CMT2 patients genetically diagnosed with different gene mutations to identify differentially regulated proteins. The candidate proteins were validated through real-time quantitative PCR and western blotting on lymphoblast samples of patients and controls, motor neurons differentiated from patient-derived induced pluripotent stem cells (iPSCs) and sciatic nerves of CMT2 mouse models.ResultsProteomic profiling of patient lymphoblasts resulted in the identification of profilin 2 (PFN2) and guanidinoacetate methyltransferase (GAMT) as commonly downregulated proteins in different genotypes compared with healthy controls. This decrease was also observed at the transcriptional level on screening 43 CMT2 patients and 22 controls, respectively. A progressive decrease in PFN2 expression with age was observed in patients, while in healthy controls its expression increased with age. Reduced PFN2 expression was also observed in motor neurons differentiated from CMT2 patient-derived iPSCs and sciatic nerves of CMT2 mice when compared with controls. However, no change in GAMT levels was observed in motor neurons and CMT2 mouse-derived sciatic nerves.ConclusionsWe unveil PFN2 and GAMT as molecular determinants of CMT2 with possible indications of the role of PFN2 in the pathogenesis and disease progression. This is the first study describing biomarkers that can boost the development of therapeutic strategies targeting a wider spectrum of CMT2 patients.
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- Kumari, Sulakshna, et al.
(författare)
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Integration of GaAs-based VCSEL array on SiN platform with HCG reflectors for WDM applications
- 2015
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Ingår i: Proceedings of SPIE - The International Society for Optical Engineering. - : SPIE. - 0277-786X .- 1996-756X. - 9781628414622 ; 9372, s. Art. no. 93720U-
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Konferensbidrag (refereegranskat)abstract
- We present a GaAs-based VCSEL structure, BCB bonded to a Si3N4 waveguide circuit, where one DBR is substituted by a free-standing Si3N4 high-contrast-grating (HCG) reflector realized in the Si3N4 waveguide layer. This design enables solutions for on-chip spectroscopic sensing, and the dense integration of 850-nm WDM data communication transmitters where individual channel wavelengths are set by varying the HCG parameters. RCWA shows that a 300nm-thick Si3N4 HCG with 800nm period and 40% duty cycle reflects strongly (
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