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| 13. |
- Lehmann, O. J., et al.
(författare)
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Novel anterior segment phenotypes resulting from forkhead gene alterations: Evidence for cross-species conservation of function
- 2003
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Ingår i: Investigative Ophthalmology & Visual Science. - : Association for Research in Vision and Ophthalmology (ARVO). - 0146-0404 .- 1552-5783. ; 44:6, s. 2627-2633
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Tidskriftsartikel (refereegranskat)abstract
- PURPOSE. Mutations in murine and human Versions of an ancestrally related gene usually result in similar phenotypes. However, interspecics differences exist, and in the case of two forkhead transcription factor genes (FOXC1 and FOXC2), these differences include corneal or anterior segment phenotypes, respectively. This study was undertaken to determine whether such discrepancies provide an opportunity for identifying novel human-murine ocular phenotypes. METHODS. Four pedigrees with early-onset glaucoma phenotypes secondary to segmental chromosomal duplications or deletions encompassing FOXC1 and 18 individuals from 9 FOXC2 mutation pedigrees underwent detailed ocular phenotyping. Subsequently, mice with mutations in Foxc1 or a related forkhead gene, Foxe3, were assessed for features of the human phenotypes. RESULTS. A significant increase in central corneal thickness was present in affected individuals from the segmental duplication pedigrees compared with their unaffected relatives (mean increase 13%, maximum 35%, P < 0.05). Alterations in corneal thickness were present in mice heterozygous and homozygous for Foxe3 mutations but neither in Foxc1 heterozygotes nor the small human segmental deletion pedigree. Mutations in FOXC2 resulted in ocular anterior segment anomalies. These were more severe and prevalent with mutations involving the forkhead domain. CONCLUSIONS. Normal corneal development is dependent on the precise dose and levels of activity of certain forkhead transcription factors. The altered corneal thickness attributable to increased forkhead gene dosage is particularly important, because it may affect the clinical management of certain glaucoma subtypes and lead to excessive treatment. The FOXC1 and Foxe3 data, taken together with the novel ocular phenotypes of FOXC2 mutations, highlight the remarkable cross-species conservation of function among forkhead genes.
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| 14. |
- Nordén, Rickard, 1977, et al.
(författare)
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Recombinant Glycoprotein E of Varicella Zoster Virus Contains Glycan-Peptide Motifs That Modulate B Cell Epitopes into Discrete Immunological Signatures
- 2019
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Ingår i: International Journal of Molecular Sciences. - : MDPI AG. - 1422-0067. ; 20:4
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Tidskriftsartikel (refereegranskat)abstract
- A recombinant subunit vaccine (Shingrix((R))) was recently licensed for use against herpes zoster. This vaccine is based on glycoprotein E (gE) of varicella zoster virus (VZV), the most abundantly expressed protein of VZV, harboring sites for N- and O-linked glycosylation. The subunit vaccine elicits stronger virus-specific CD4+ T cell response as well as antibody B cell response to gE, compared to the currently used live attenuated vaccine (Zostavax((R))). This situation is at variance with the current notion since a live vaccine, causing an active virus infection, should be far more efficient than a subunit vaccine based on only one single viral glycoprotein. We previously found gE to be heavily glycosylated, not least by numerous clustered O-linked glycans, when it was produced in human fibroblasts. However, in contrast to Zostavax((R)), which is produced in fibroblasts, the recombinant gE of Shingrix((R)) is expressed in Chinese hamster ovary (CHO) cells. Hence, the glycan occupancy and glycan structures of gE may differ considerably between the two vaccine types. Here, we aimed at (i) defining the glycan structures and positions of recombinant gE and (ii) identifying possible features of the recombinant gE O-glycosylation pattern contributing to the vaccine efficacy of Shingrix((R)). Firstly, recombinant gE produced in CHO cells (Shingrix situation) is more scarcely decorated by O-linked glycans than gE from human fibroblasts (Zostavax situation), with respect to glycan site occupancy. Secondly, screening of immunodominant B cell epitopes of gE, using a synthetic peptide library against serum samples from VZV-seropositive individuals, revealed that the O-linked glycan signature promoted binding of IgG antibodies via a decreased number of interfering O-linked glycans, but also via specific O-linked glycans enhancing antibody binding. These findings may, in part, explain the higher protective efficacy of Shingrix((R)), and can also be of relevance for development of subunit vaccines to other enveloped viruses.
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| 15. |
- Risinger, C., et al.
(författare)
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Linear Multiepitope (Glyco)peptides for Type-Specific Serology of Herpes Simplex Virus (HSV) Infections
- 2017
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Ingår i: Acs Infectious Diseases. - : American Chemical Society (ACS). - 2373-8227. ; 3:5, s. 360-367
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Tidskriftsartikel (refereegranskat)abstract
- Detection of type-specific antibodies is an important and essential part of accurate diagnosis, even in silent carriers of herpes simplex virus (HSV)-1 (oral) and HSV-2 (genital) infections. Serologic assays that identify HSV-1 and HSV-2 type-specific antibodies have been commercially available for more than a decade but often face problems related to cross-reactivity and similar issues. Attempts to identify type-specific peptide epitopes for use in serology for both HSV-1 and HSV-2 have been limited. We recently demonstrated epitope mapping of envelope glycoprotein G2 and identified a type-specific glycopeptide epitope that broadly recognized HSV-2 infected individuals. In the present work we have performed a comprehensive glycopeptide synthesis and rnicroarray epitope mapping of 14 envelope proteins from HSV-1 and HSV-2, namely, gB, gC, gD, gE, gG, gH, and gI, using sera from HSV-1-and HSV-2-infected individuals and control sera. Several unique type-specific peptide epitopes with high sensitivity were identified and synthesized as one large linear multiepitope sequence using microwave-assisted solid-phase (glyco)peptide synthesis. Microarray validation with clinically defined HSV and Varicella Zoster (VZV) sera confirmed excellent cumulative specificities and sensitivities.
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| 16. |
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| 18. |
- Silfvenius, Christofer, et al.
(författare)
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Nitride facet passivation raises reliability, COMD, and enables high-temperature operation of InGaAsP, InGaAs, and InAlGaAs lasers
- 2005
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Ingår i: High-Power Diode Laser Technology and Applications III. - : SPIE. ; , s. 189-200
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Konferensbidrag (refereegranskat)abstract
- The laser diode technology, underpinning applications such as data storage, industrial lasers and optical telecommunications, still suffers from reliability and longevity limitations, especially in high power applications. A main problem for these lasers arises from facet oxidation, leading to increased absorption, power degradation and COMD device failure. Typically, high power devices initially show a low linear degradation and after some 100 hours, the degradation accelerates in a nonlinear fashion, indicating a degradation runaway condition. This article reports performance and reliability improvements that are based on a process which atomically seals surfaces and eliminates oxidation by forming stable nitrides on laser facets. The dangling bond terminating technology suppresses accelerated degradation associated with optical density and heat at laser facets. The dangling bond termination is demonstrated by improved COMD, decreased degradation at CW operation and a constant linear degradation rate at different QW temperature conditions (nonlinear degradation indicates advancement in the oxidation/optical absorption/facet heating/oxidation spiral). The technology is applicable to a range of material systems and has previously been demonstrated on InAlGaAs and InGaAs (increased COMD to >270 and 470mW/μm respectively). The devices with the typically lowest COMD levels (AlInGaAs) show a remarkably low linear degradation rate of <0.5%/kh during at CW life test operation at 90°C and a power level corresponding to 80W bar power. In addition to long term AlInGaAs laser life test results, this paper presents results on nitride facet passivation applied to 805nm InGaAsP devices, showing improved COMD to 400mW/μm and the initial CW life data confirms the general behavior of the previously life-tested InGaAs and InAlGaAs based devices.
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| 19. |
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