Adeno-associated viruses (AAV) are among the leading vectors for in vivo gene therapy. The purification of AAV remains a bottleneck as it typically requires multiple individual process steps, often resulting in product loss and high costs. Current downstream processes are usually serotype-specific and rely primarily on expensive affinity resins.
View Article and Find Full Text PDFUridine diphosphate N-acetylglucosamine 2-epimerase (GNE) is a key enzyme in the sialic acid biosynthesis pathway. Sialic acids are primarily terminal carbohydrates on glycans and play fundamental roles in health and disease. In search of effective GNE inhibitors not based on a carbohydrate scaffold, we performed a high-throughput screening campaign of 68,640 drug-like small molecules against recombinant GNE using a UDP detection assay.
View Article and Find Full Text PDFSialic acids are part of the outermost component of the glycocalyx of all vertebrates; as such, they are fundamental markers in physiological and pathological processes. In this study, we introduce a real-time assay to monitor individual enzymatic steps of sialic acid biosynthesis, either with recombinant enzymes, in particular using UDP--acetylglucosamine 2-epimerase (GNE) or -acetylmannosamine kinase (MNK), or in cytosolic rat liver extract. Using state-of-the-art NMR techniques, we are able to follow the characteristic signal of the -acetyl methyl group, which displays different chemical shifts for the biosynthesis intermediates UDP--acetylglucosamine, -acetylmannosamine (and its 6-phosphate) and -acetylneuraminic acid (and its 9-phosphate).
View Article and Find Full Text PDFThe combination of radiotherapy (RT) and chemotherapy (CT) is the main treatment modality of limited-stage small cell lung cancer (SCLC). The application of radiation timing, doses, fraction schedules in this modality and the indication of prophylactic cranial irradiation is recently controversial. In this retrospective study, these subjects were evaluated by considering our patients results.
View Article and Find Full Text PDFDeclining use of the services of local dispensaries has often been suggested as a significant factor in the rising trend of tuberculosis in Turkey after 1970. Data confirming this view were insufficient until this study, which consists of an evaluation of the records of 51,086 subjects seen by the tuberculosis dispensary in Elaziğ between 1985-1989. We found that, despite an expected yearly population increase, there were no significant differences in the numbers of diagnostic and follow-up procedures as well as preventive and therapeutic interventions recorded in different years, and that cases of active tuberculosis lost to follow-up had gradually increased.
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