Biophysical Analysis of the C9orf72 Hexanucleotide Repeat Associated with ALS/FTD

Amyotrophic lateral sclerosis (ALS) and frontotemporal dementia (FTD) are two extremes of a spectrum of neurodegenerative disorders. Recently, it was shown that expansion of (GGGGCC)n. (GGCCCC)n in the C9orf72 gene is the main cause of ALS/FTD. Being G-rich on one strand, and C-rich on the other strand, the C9orf72 repeat is a great candidate for secondary structure formation. To date, it has been shown that different repeats of the G-rich DNA and RNA, can form G-quadruplexes in-vitro. Our studies have been mainly focused on biophysically characterizing G-rich RNA and DNA strands, and C-rich DNA strands by using CD and UV spectroscopy and gel electrophoresis. We have shown that G-rich RNA forms parallel G-quadruplexes and C-rich DNA can form an array of secondary structures including i-motifs at acidic pH, monomolecular hairpins at basic pH and G-quadruplexes at neutral pH. This range of structure is due to the ability of cytosines to get hemiprotonated. Non-canonical structures have long been known to act as mutagenic intermediates leading to genetic instability. Therefore, biophysically assessing these structures not only may provide a basis for mechanistic pathways leading to the disease, but may help find ways to prevent the disease. One of the proposed disease mechanisms is through toxic gain-of-function where neurodegeneration is caused by formation of nuclear RNA aggregates which sequester proteins. Based on this, we also identified two proteins which exhibit structure-specific binding to the RNA G-quadruplexes. Subsequently, we offered proof-of-principle of a ligand-based therapeutic approach where TMPyP4, a G-quadruplex binding ligand, was shown to disrupt the interaction between the RNA G-quadruplexes and ASF/SF2 and hnRNPA1. Lastly, we studied the effect of methylation on the secondary structures formed by the repeat. Recently, it was shown that the repeat itself is methylated in ALS patients, which also rationalized the observed 50% transcription reduction seen in expansion carriers. We have shown that while methylation at CpG sites stabilizes the structures on both G-rich and C-rich DNA strands, hydroxymethylation destabilizes them.Ph.D

Assessment of the effects of bean extract on axillary hair reduction

Objective: Body hair removal plays an important role in beauty standards, particularly for women. Finding a method that is easy to use, cheap, and can be done without supervision can significantly affect long-term hair reduction and reduce the side effects of hair removal. The present study investigated the impact of a containing 20% broad bean (Vicia faba) extract cream on axillary hair removal.Materials and Methods: Twenty-five female volunteers were randomly divided into A (right axillary intervention - left axillary placebo) and B (right axillary placebo - left axillary intervention). Depending on the group, each person used a cream containing 20% broad bean extract )"The extract made from the seeds and pods of broad beans.") on one side and a placebo on the other twice a day for three months. Volunteers shaved their axillary hairs three days before each visit and took pictures of both sides on the day of the visit with a trichoscope (to check the diameter and thickness of the hairs).Results: We found a decrease in thickness on the intervention group (the axilla where a cream containing broad bean extract was applied); however, this difference was not significant between the intervention side and the placebo. In terms of the number of hairs, the difference between the two groups was significant only in the second month despite the decrease on the intervention side. Evaluation based on the personal judgment of the volunteers showed that there was a substantial difference in terms of the number of hairs (p=0.012) and thinning of hair (p=0.02).Conclusion: Our findings showed that 20% broad bean extract cream could potentially reduce axillary hair growth