In Vitro Interaction of a C-Terminal Fragment of TDP-43 Protein with Human Serum Albumin Modulates Its Aggregation.

An increased level of naturally occurring anti-TDP-43 antibodies was observed in the serum and cerebrospinal fluid (CSF) of amyotrophic lateral sclerosis patients. Human serum albumin (HSA), the most abundant protein in blood plasma and CSF, is found to interact with pathological proteins like Aß and α-synuclein. Therefore, we examined the effect on the in vitro aggregation of a C-terminal fragment of TDP-43 in the presence of HSA. We found that the lag phase in TDP-432C aggregation is abrogated in the presence of HSA, but there is an overall decreased aggregation as examined by thioflavin-T fluorescence spectroscopy and microscopy. An early onset of TDP-432C oligomer formation in the presence of HSA was observed using atomic force microscopy and transmission electron microscopy. Also, a known chemical inhibitor of TDP-432Caggregation, AIM4, abolishes the HSA-induced early formation of TDP-432C oligomers. Notably, the aggregates of TDP-432C formed in the presence of HSA are more stable against sarkosyl detergent. Using affinity copurification, we observed that HSA can bind to TDP-432C, and biolayer interferometry further supported their physical interaction and suggested the binding affinity to be in sub-micromolar range. Taken together, the data support that HSA can interact with TDP-432C in vitro and affect its aggregation.

Solitary juvenile polyps in children and colon cancer.

BACKGROUND/AIMS: Solitary Juvenile Polyps (SJP) are quite common in preschool children, although they may occur at any age. It is not known whether the existence of a single juvenile polyp in a child predisposes to future development of new SJP or is related to colorectal neoplasia. The present study was designed to follow up young patients who had undergone polypectomy for SJP and their first degree relatives to elucidate the development of adenomatous polyps or colon cancer. MATERIALS AND METHODS: From 31 children polypectomized for histologically proven SJP between 1983-1995, we were able to contact and gather information on 24. From our records and the information collected we studied age, gender, site of the polyp in the bowel, personal history, and family history. RESULTS: Mean time of follow up was 4.1 years (range 0.4-10, SD +/- 3.1) Mean age was 4.6 years (Range 3.5-9, SD +/- 1.2). There were 14 boys and 10 girls (ratio 1.4/1). Eighteen polyps were located at the rectosigmoid area, 5 in the lower descending colon, and one in the splenic flecture. From the 24 children, only one girl developed rectal bleeding at the age of 15 years, 8 years after polypectomy. However, subsequent evidence from the large bowel did not reveal any abnormality and the symptom was attributed to hemorrhoidal bleeding. Thorough investigation of the history of 146 first degree relatives (dead or alive) siblings, parents, and grandparents revealed that none of them were diagnosed with adenomatous polyps or colorectal cancer. CONCLUSION: SJP does not predispose to future development of new juvenile polyps and is not associated with a high risk of colorectal malignancy.