We studied the effect of reduced tryptophan hydroxylase (TPH) activity and short daylight exposure on the behavior and the 5-HT system of the brain in
D. rerio
. Male and female
D. rerio
were exposed ...for 30 days to standard (12:12 h light:dark) and short (4:20 h light:dark) photoperiods in the presence or absence of TPH inhibitor (
p
-chlorophenylalanine, pCPA, 5 mg/liter). On day 31, the fish behavior in the “novel tank diving” test, their sex and body weight were determined, and the levels of pCPA, 5-HT, and its metabolite 5-HIAA were measured by HPLC; the levels of the key genes encoding metabolism enzymes (
Tph1a
,
Tph1b
,
Tph2
, and
Mao
) and receptors of 5-HT (
Htr1aa
,
Htr2aa
) were assessed by real-time PCR with reverse transcription. The short daylight exposure caused masculinization of females, reduced body weight, and motor activity in the “novel tank diving” test, but did not affect the 5-HT system of the brain. Long-term pCPA treatment had no effect on sex and body weight, significantly reduced the 5-HIAA level, but increased
Tph1a
and
Tph2
gene expression in the brain. No effects of the interaction of short daylight and pCPA exposure on the sex, body weight, behavior, and 5-HT system of the brain were found. Thus, a moderate decrease in TPH activity cannot potentiate the negative effects of short daylight exposure on the sex, body weight, behavior, and 5-HT system of
D. rerio
.
We present rapid and sensitive assay of tryptophan hydroxylase 2 enzyme activity based on the fluorescence of the complex of 5-hydroxytryptophan (5-HTP) with
o
-phthalic aldehyde. This method was ...compared with the standard method based on chromatographic isolation of 5-HTP followed by its quantification using an electrochemical detector. High sensitivity of the developed fluorometric method and similarity of the results obtained by fluorometric and chromatographic methods were demonstrated. The use of this rapid, cheap, and effective fluorometric method can simplify and facilitate measurements of tryptophan hydroxylase 2 activity and can make this assay available for a wide range of neurochemical and pharmacological laboratories.
On November 18, 1929, a
M=7.2 earthquake occurred at the southern edge of the Grand Banks, 280 km south of Newfoundland. The earthquake triggered a large submarine slope failure (200 km
3), which was ...transformed into a turbidity current carrying mud and sand eastward up to 1000 km at estimated speeds of about 60–100 km/h, breaking 12 telegraph cables. The tsunami generated by this failure killed 28 people, making it the most catastrophic tsunami in Canadian history. Tsunami waves also were observed along other parts of the Atlantic coast of Canada and the United States. Waves crossing the Atlantic were recorded on the coasts of Portugal and the Azores Islands. Tsunami waves had amplitudes of 3–8 m and runup of up to 13 m along the coast of the Burin Peninsula (Newfoundland). To simulate the slide-generated tsunami from this event, our initial analysis uses a shallow-water model; the slide was assumed to be a viscous, incompressible fluid layer; water was inviscid and incompressible. The preliminary results of the numerical modeling are encouraging, with computed and observed tsunami arrival times in reasonable agreement.
The effect of membrane thickness on the parameters of high-purity hydrogen production in a membranecatalytic device from a mixture of methane and water vapor has been analysed in detail using the ...method of mathematical simulation under standard initial conditions. A linear dependence of the average density of the hydrogen diffusion flux through the membrane on the membrane inverse thickness has been established.
The enzyme tryptophan hydroxylase 2 (TPH2) catalyzes the hydroxylation of L-tryptophan to L-5-hydroxytryptophan (5-HTP), the first and the key step in 5-HT synthesis in the mammalian brain. Mutations ...in the human
Tph2
gene reducing enzyme activity increase the risk of psychopathology. Pharmacological chaperones are small molecules that can specifically bind to mutant protein molecules, restore their disturbed 3D structure to the native state, and increase their stability and functional activity. The chaperone activity of (R)-2-amino-6-(1R,2S)-1,2-dihydroxypropyl)-5,6,7,8-tetrahydropterin-4(3H)-one (BH
4
) is expressed by increasing the
in vitro
thermal stability of mutant tyrosine hydroxylase and phenylalanine hydroxylase molecules which are similar to TPH2 in their structure and characteristics. The
P447R
substitution in the mouse TPH2 molecule results in a 2-fold decrease in enzyme activity in their brains. We studied the effect of this mutation on the TPH2 thermal stability, as well as on the ability of BH
4
and its 8 structural analogues to increase the thermal stability of the mutant TPH2 from midbrain extracts of BALB/C mice. Temperature stability was studied by the decrease in enzyme activity during its heating for 2 min at increasing temperatures and was evaluated by the T
50
value that is the temperature at which the enzyme activity decreased by half. For the mutant TPH2, the T
50
value was decreased compared to the wild type enzyme. BH
4
and its closest structural analogue, 6-methyl-5,6,7,8-tetrahydropterin, increased the T
50
value,
i.e.
, exhibited chaperone activity. Other close BH
4
analogs, 6,7-dimethyl-5,6,7,8-tetrahydropterin and folic acid, were not effective. It can be assumed that BH
4
can be effective in the treatment of mental disorders caused by mutations in the
Tph2
gene.
A computational example demonstrates the possibility of using a mathematical model, physically substantiated and verified on a sufficient amount of experimental data, for design calculations of high ...productivity membrane catalytic devices for obtaining high-purity hydrogen from hydrocarbon raw materials, and individual low productivity membrane-catalytic modules of any geometric shape required for their arrangement.
It was found by mathematical modeling method that increase in volume flow rate of initial hydrocarbon-steam mixture, with the process and design parameters of the membrane-catalytic device remaining ...unchanged, markedly affects the increase of high-purity hydrogen production capacity of the device with a slight decrease of hydrogen extraction efficiency.
Mathematical modeling is used to analyze results of laboratory studies of a tubular type membranecatalytic module for high-purity hydrogen production from natural gas. It is shown that the ...mathematical model can almost exactly describe the experimental data.
The effects of temperature and pressure on both sides of the membrane on the efficiency of hydrogen production are estimated by mathematical modeling using as examples two types of membrane-catalytic ...devices for high-purity hydrogen production from hydrocarbon feedstocks with different methods of removing the hydrogen product. Graphs of the results are convenient for prompt selection of the optimal operating temperatures and pressures for producing high-purity hydrogen with a high volumetric yield.
Comparative analysis confirmed the effect of additional factor related with the system of high-purity hydrogen removal from flat-type membrane components on the indicators of hydrogen production from ...hydrocarbons in membrane-catalytic devices.
