Biotin-Lys-His Blocks Aggregation of RNA-binding Protein TLS, a Cause of Amyotrophic Lateral Sclerosis
Naomi Ueda,
Gengo Kashiwazaki,
Toshikazu Bando,
Riki Kurokawa
Issue:
Volume 3, Issue 4, July 2017
Pages:
67-77
Received:
10 August 2017
Accepted:
30 August 2017
Published:
12 September 2017
Abstract: RNA-binding protein TLS/FUS is a causative gene for amyotrophic lateral sclerosis (ALS) and frontotemporal lobar degeneration (FTLD). TLS mutations induce the propensity of TLS to form aggregates in motor neurons causing neuronal degenerative lesions to their necrosis. TLS is prone to be precipitated in high concentration around 10 mg/ml, while mutated TLS is suspected to be precipitated even lower or physiological concentration in the motor neurons. An unidentified agent from infections would cause formation of the precipitation of TLS through their surface antigens. The precipitation driven with agents might be attribute to a small compound appeared on the surface. Biotinylated isoxazole (BISOX) has been reported to be precipitated with divergent RNA-binding proteins including TLS in nuclear extracts of cultured mammalian cells. We have published a molecular model for crystal formation of BISOX with TLS providing a plat form for searching novel regulators to precipitate TLS in neuronal disorders. Because BISOX is an artificial compound, we have further explored to obtain naturally occurring agents to induce the TLS precipitation and generated a conceivable biological compound, biotin-Lys-His (BLH). We have examined the precipitation of BLH with HeLa cell nuclear extract, but did not detect any TLS signal. Then, we add BLH to reaction of BISOX with TLS, and serendipitously observed a robust inhibitory effect of BLH on the formation of crystal of BISOX with TLS. We employed in silico analysis to show how BLH blocks the crystal formation of BISOX with TLS. The computational analysis of the events presented a model that BLH should be incorporated into the crystal formation of BISOX but some steric hindrance placed by BLH blocks growing of the crystal of BISOX and TLS. These results provide the potentiality that BLH should block the aggregate formation of TLS in ALS, leading to a seed for drug discovery against ALS, although it needs future endeavor to find more compounds to have effect on the TLS aggregation.
Abstract: RNA-binding protein TLS/FUS is a causative gene for amyotrophic lateral sclerosis (ALS) and frontotemporal lobar degeneration (FTLD). TLS mutations induce the propensity of TLS to form aggregates in motor neurons causing neuronal degenerative lesions to their necrosis. TLS is prone to be precipitated in high concentration around 10 mg/ml, while mut...
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Biological Effects of Magnetic Water on Human and Animals
Shaban Ali Ebrahim,
Azab Elsayed Azab
Issue:
Volume 3, Issue 4, July 2017
Pages:
78-85
Received:
22 August 2017
Accepted:
31 August 2017
Published:
12 September 2017
Abstract: The aim of the present study was to investigate the beneficial effects of magnetized water for human and animals. There was an improvement in water quality when exposed to the magnetic field with considerable change in the pH, total dissolved solids, total hardness, conductivity, salinity, dissolved oxygen, evaporating temperature, minerals, organic matter and total count of bacteria. Therefore it’s penetration into cell wall would be facilitated which can accelerate ordinary diffusion of water that is vital for growth of different organs. Patients uses magnetic water for digestive, urinary and nervous problems, ailments like mastitis, pains and swellings, painful urination and many other disorders. Magnetized water has been found effective in alleviating colds, coughs, bronchitis, all types of fever and more, arthritis pain, reducing blood pressure, recovering quickly from a stroke, and it helpful in the regularization of women's menses. Also, treatment with magnetic water was very effective in breaking up kidney and gall bladder stones into small particles. The water also prevented further formation of stones in the kidneys and gallbladder. Magnetic water may prevent aging and fatigue by increasing the cell membrane permeability. Effectiveness of magnetized water in the prevention and treatment of atherosclerosis has been shown in some animal and human studies. It has been reported that magnetic water help unclog the arteries and veins of deposits of cholesterol and salts and normalize the circulatory system. Also, magnetized water can be helpful in weight control, as an adjutant to a correct diet because this water improves metabolic activity, it may be helpful in burning up excessive fatty tissue. Magnetized drinking water improves nutrient digestibility, saves water consumption, optimizing rumen fermentation parameters, and it could an effective way to reduce methane production and contributing to mitigate environmental impact in livestock, positive animal health, which is reflected in the increase in milk yield and its component and improves blood picture and antioxidant status. Magnetized drinking water caused increase milk production, mutton, and wool in sheep not only that, but more weight gain in geese and egg production and hatchability in turkey can be achieved, and increasing in milk yields in dairy cows and ewes. It can be concluded that magnetic water treatment improved blood picture, biochemical parameters, semen quality, and antioxidant status in human and animals. So, magnetic water must be used to mitigate the harmful effects of drugs, toxins, and environmental pollutant on human and animals.
Abstract: The aim of the present study was to investigate the beneficial effects of magnetized water for human and animals. There was an improvement in water quality when exposed to the magnetic field with considerable change in the pH, total dissolved solids, total hardness, conductivity, salinity, dissolved oxygen, evaporating temperature, minerals, organi...
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