Mutations in the DNA of somatic cells, resulting from inaccuracies in DNA<br/>replication or exposure to harsh conditions (ionizing radiation, carcinogens), may be<br/>loss-of-function mutations, and the compounding of these mutations can lead to cancer.<br/>Such mutations can come in the form of thymine dimers, N-đť›˝ glycosyl bond hydrolysis,<br/>oxidation by hydrogen peroxide or other radicals, and deamination of cytosine to uracil.<br/>However, many cells possess the machinery to counteract the deleterious effects of<br/>such mutations. While eukaryotic DNA repair enzymes decrease the incidence of<br/>mutations from 1 mistake per 10^7 nucleotides to 1 mistake per 10^9 nucleotides, these<br/>mutations, however sparse, are problematic. Of particular interest is a mutation in which<br/>uracil is incorporated into DNA, either by spontaneous deamination of cysteine or<br/>misincorporation. Such mutations occur about one in every 107 cytidine residues in 24<br/>hours. DNA uracil glycosylase (UDG) recognizes these mutations and cleaves the<br/>glycosidic bond, creating an abasic site. However, the rate of this form of DNA repair<br/>varies, depending on the nucleotides that surround the uracil. Most enzyme-DNA<br/>interactions depend on the sequence of DNA (which may change the duplex twist),<br/>even if they only bind to the sugar-phosphate backbone. In the mechanism of uracil<br/>excision, UDG flips the uracil out of the DNA double helix, and this step may be<br/>impaired by base pairs that neighbor the uracil. The deformability of certain regions of<br/>DNA may facilitate this step in the mechanism, causing these regions to be less<br/>mutable. In DNA, base stacking, a form of van der Waals forces between the aromatic<br/>nucleic bases, may make these uracil inclusions more difficult to excise. These regions,<br/>stabilized by base stacking interactions, may be less susceptible to repair by<br/>glycosylases such as UDG, and thus, more prone to mutation.
Exploring Structure and Function of Human Cold Sensing Protein TRPM8 with ROSETTA Comparative Models
The experiment was conducted to analyze the role of menaquinone (MQ) in heliobacteria’s reaction center (HbRC). Their photosynthetic apparatus is a homodimeric of type I reaction center (1). HbRC contains these cofactors: P800 (special pair cholorphyll), A0 (8-hydroxy-chlorophyll [Chl] a), and FX (iron-sulfur cluster). The MQ factor is bypassed during the electron transfer process in HbRC. Electrons from the excited state of P800 (P800*) are transported to A0 and then directly to Fx. The hypothesis is that when electrons are photoaccumulated at Fx, and without the presence of any electron acceptors to the cluster, they would be transferred to MQ, and reduce it to MQH2 (quinol). Experiments conducted in the past with HbRC within the cell membranes yielded data that supported this hypothesis (Figures 4 and 5). We conducted a new experiment based on that foundation with HbRC, isolated from cell membrane. Two protein assays were prepared with cyt c553 and ascorbate in order to observe this phenomenon. The two samples were left in the glove box for several days for equilibration and then exposed to light in different intensity and periods. Their absorption was monitored at 800 nm for P800 or 554 nm for cyt c553 to observe their oxidation and reduction processes. The measurements were performed with the JTS-10 spectrophotometer. The data obtained from these experiments support the theory that P800+ reduced by the charge recombination of P800+Fx-. However, it did not confirm the reduction of P800+ done by cyt c553¬ which eventually lead to a net accumulation of oxidized cyt c553; instead it revealed another factor that could reduce P800+ faster and more efficient than cyt c553 (0.5 seconds vs several seconds), which could be MQ. More experiments need to be done in order to confirm this result. Hence, the data collected from this experiment have yet to support the theory of MQ being reduced to MQH2 outside the bacterial membranes.
In 2017-2018, the results showed that 0.5% menthol (n=4) suppressed weight gain more effectively than both the baseline chow diet (n=4, p=0.022) and the HFD (n=4, p=0.027). Again in 2018-2020, the 0.5% menthol (n=6) showed promising results, showing significant suppression of weight gain when compared to chow (n=13, p=0.022). Unfortunately, the difference in weight gain in 1% menthol (n=6) was inconclusive when comparing to both chow and HFD. Although 1% menthol was inconclusive in its efficacy in suppressing weight regain, the promising results on 0.5% menthol show that menthol has the potential to be an effective treatment to both prevent rapid weight gain and maintain weight loss from caloric restriction.