Using liquid chromatography/electrospray ionization mass spectrometry, we have found three unconjugated bile acids [cholic acid (CA), chenodeoxycholic acid (CDCA), and deoxycholic acid (DCA)] in the rat brain cytoplasmic fraction. CDCA was detected only upon extraction with high concentrations of guanidine, indicating that it is bound noncovalently to protein in the brain. The most abundant of the three, it was present at a concentration of 1.6 nmol/g wet weight ( ف 15 mg of protein) of brain, corresponding to almost 30 times its serum concentration. CA and DCA were present at 1/30th the concentration of CDCA. Bile acids conjugated with amino acids, sulfuric acid, and glucuronic acid were not detected. These data clearly demonstrate that unconjugated CDCA and, to a lesser extent, CA and DCA, exists in the rat brain. Bile acids are synthesized in the liver from cholesterol by the action of hepatic enzymes and excreted into the small intestine via the bile duct. In the intestinal lumen, they assist lipolysis and the absorption of fats by forming mixed micelles and then return to the liver upon absorption in the ileum and proximal colon. Because of their efficient hepatic uptake, bile acids have low concentrations in the peripheral blood. Recent observations also indicate that the nuclear bile acid receptor, the farnesoid X receptor, regulates the bile acid pool by repressing the transcription of genes encoding hepatocyte transporters (1) as well as cholesterol 7 ␣ -hydroxylase (2, 3), which is the ratelimiting enzyme for bile acid biosynthesis.
DIAPH1 encodes human DIA1, a formin protein that elongates unbranched actin. The c.3634+1G>T DIAPH1 mutation causes autosomal dominant nonsyndromic sensorineural hearing loss, DFNA1, characterized by progressive deafness starting in childhood. The mutation occurs near the C‐terminus of the diaphanous autoregulatory domain (DAD) of DIA1, which interacts with its N‐terminal diaphanous inhibitory domain (DID), and may engender constitutive activation of DIA1. However, the underlying pathogenesis that causes DFNA1 is unclear. We describe a novel patient‐derived DIAPH1 mutation (c.3610C>T) in two unrelated families, which results in early termination prior to a basic amino acid motif (RRKR
1204–1207) at the DAD C‐terminus. The mutant DIA1(R1204X) disrupted the autoinhibitory DID‐DAD interaction and was constitutively active. This unscheduled activity caused increased rates of directional actin polymerization movement and induced formation of elongated microvilli. Mice expressing FLAG‐tagged DIA1(R1204X) experienced progressive deafness and hair cell loss at the basal turn and had various morphological abnormalities in stereocilia (short, fused, elongated, sparse). Thus, the basic region of the DAD mediates DIA1 autoinhibition; disruption of the DID‐DAD interaction and consequent activation of DIA1(R1204X) causes DFNA1.
The aim of this paper is to demonstrate the capabilities of a new automated analysis scheme developed for meteor head echo observations by the Shigaraki middle and upper atmosphere (MU) radar in Japan (N, E). Our analysis procedure computes meteoroid range, velocity and deceleration as functions of time with unprecedented accuracy and precision. This is crucial for estimations of meteoroid mass and orbital parameters, as well as investigations into meteoroid–atmosphere interaction processes. We collected an extensive set of data (>500 h) between 2009 June and 2010 December. Here, we present initial results from data taken in 2009 October 19–21. More than 600 of about 10 000 head echoes recorded during 33 h were associated with the 1P/Halley dust of the Orionid meteor shower. These meteors constitute a very clear enhancement of meteor radiants centred around right ascension α= and declination δ=. Their estimated atmospheric entry velocity of 66.9 km s−1 is in good agreement with 1P/Halley dust ejected in the year 1266 bc, which, according to simulations, crossed Earth’s orbit at the time of our observation. The Orionid activity within the MU radar beam reached about 50 h−1 during radiant culmination. The flux of sporadic meteors in the MU radar data, coming primarily from the direction of the Earth’s apex, peaked at about 700 h−1 during the same observations.
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