Effects of vitamin B12 on plasma melatonin rhythm in humans: increased light sensitivity phase-advances the circadian clock?

Vitamin B12 (methylcobalamin) was administered orally (3 mg/day) to 9 healthy subjects for 4 weeks. Nocturnal melatonin levels after exposure to bright light (ca. 2500 lx) were determined, as well as the levels of plasma melatonin over 24 h. The timing of sleep was also recorded. Vitamin B12 was given blind to the subjects and crossed over with placebo. We found that the 24-h melatonin rhythm was significantly phase-advanced (1.1 h) in the vitamin B12 trial as compared with that in the placebo trial. In addition, the 24-h mean of plasma melatonin level was much lower in the vitamin B12 trial than with the placebo. Furthermore, the nocturnal melatonin levels during bright light exposure were significantly lower in the vitamin B12 trial than with the placebo. On the other hand, vitamin B12 did not affect the timing of sleep. These findings raise the possibility that vitamin B12 phase-advances the human circadian rhythm by increasing the light sensitivity of the circadian clock.     

Seasonality in human sleep.

The timing of sleep and sleep EEG parameters in 10 healthy male subjects were investigated in four seasons under controlled conditions. The phase of nocturnal sleep was delayed about one and a half hours in winter as compared to that in summer. The duration of stage 4 sleep decreased and REM sleep increased significantly in winter compared with summer. The seasonality in the timing of sleep can be explained by photoperiodic time cues, but the changes in sleep EEG parameters are difficult to explain in terms of photoperiod.     

Heterogeneous responses of canine basilar and middle cerebral arteries to serotonin at normal and high CO2 tension

The responses of basilar arteries (BAs) to serotonin were attenuated by high \(P_{CO_2 } \) (86±1 mm Hg) and the pH matched acidotic solution ( \(P_{CO_2 } \) 37±1 mm Hg), whereas the responses of middle cerebral arteries (MCAs) were not. High \(P_{CO_2 } \) decreased the basal tone of both arteries, and the changes in basal tone due to high \(P_{CO_2 } \) were not influenced by 3×10^?7 M imipramine, 10^?5 M pargyline or 10^?4 M aspirin. The responses of BAs to serotonin were attenuated by high \(P_{CO_2 } \) in the presence of imipramine, pargyline and aspirin. The responses of MCAs to serotonin were not influenced by high \(P_{CO_2 } \) in the presence of pargyline and aspirin, but attenuated by high \(P_{CO_2 } \) in the presence of imipramine.     

管材超声检测中导波模式及频厚积的选择

用轴向功率流分布来选择检测自由管状结构的最佳导波模式及其最佳频厚积 ,并将混合边界元法应用于管状结构 ,对其结果的有效性进行了验证 .结果表明 :对于自由管材 ,用超声纵向L(0 ,1)模式检测时 ,频厚积在 0 .15MHz·mm以下时较为灵敏 ;用L(0 ,2 )模式检测时 ,在 1.4～ 1.8MHz·mm之间对检测管壁中央的缺陷较灵敏 ;用L(0 ,3)模式检测时 ,在 2 .0MHz·mm以下对管内外表面上的缺陷都较灵敏 .轴向功率流分布能有效地选择检测的最佳导波模式及其频厚积 .     

肌肉自发振动过程中结合几率与化学反应速率的变化

定量分析肌球蛋白与肌动蛋白丝的结合几率及相关化学反应的速率常数,对于准确掌握肌肉收缩的内在机制具有非常重要的意义.以肌肉自发振动的实验结果为依据,从振动过程所满足的动力学方程出发,推导出结合几率与肌丝滑行速度及肌节长度之间的定量关系,并求得化学反应速率随肌肉收缩的速度变化而改变的数学规律.结果显示,结合几率的基准值由溶液中主要化学成分的浓度决定;结合几率的变化值与肌肉收缩的速度成正比,与肌节长度成反比;而化学反应速率随收缩速度按指数规律变化.上述结果与实验值基本一致.     

De novo mutations in the gene encoding STXBP1 (MUNC18-1) cause early infantile epileptic encephalopathy

Early infantile epileptic encephalopathy with suppression-burst (EIEE), also known as Ohtahara syndrome, is one of the most severe and earliest forms of epilepsy. Using array-based comparative genomic hybridization, we found a de novo 2.0-Mb microdeletion at 9q33.3-q34.11 in a girl with EIEE. Mutation analysis of candidate genes mapped to the deletion revealed that four unrelated individuals with EIEE had heterozygous missense mutations in the gene encoding syntaxin binding protein 1 (STXBP1). STXBP1 (also known as MUNC18-1) is an evolutionally conserved neuronal Sec1/Munc-18 (SM) protein that is essential in synaptic vesicle release in several species. Circular dichroism melting experiments revealed that a mutant form of the protein was significantly thermolabile compared to wild type. Furthermore, binding of the mutant protein to syntaxin was impaired. These findings suggest that haploinsufficiency of STXBP1 causes EIEE.     

A proteoglycan mediates inductive interaction during plant vascular development

Inductive cell-cell interactions are essential for controlling cell fate determination in both plants and animals; however, the chemical basis of inductive signals in plants remains little understood. A proteoglycan-like factor named xylogen mediates local and inductive cell-cell interactions required for xylem differentiation in Zinnia cells cultured in vitro. Here we describe the purification of xylogen and cloning of its complementary DNA, and present evidence for its role in planta. The polypeptide backbone of xylogen is a hybrid-type molecule with properties of both arabinogalactan proteins and nonspecific lipid-transfer proteins. Xylogen predominantly accumulates in the meristem, procambium and xylem. In the xylem, xylogen has a polar localization in the cell walls of differentiating tracheary elements. Double knockouts of Arabidopsis lacking both genes that encode xylogen proteins show defects in vascular development: discontinuous veins, improperly interconnected vessel elements and simplified venation. Our results suggest that the polar secretion of xylogen draws neighbouring cells into the pathway of vascular differentiation to direct continuous vascular development, thereby identifying a molecule that mediates an inductive cell-cell interaction involved in plant tissue differentiation.     

Functional annotation of a full-length mouse cDNA collection

The RIKEN Mouse Gene Encyclopaedia Project, a systematic approach to determining the full coding potential of the mouse genome, involves collection and sequencing of full-length complementary DNAs and physical mapping of the corresponding genes to the mouse genome. We organized an international functional annotation meeting (FANTOM) to annotate the first 21,076 cDNAs to be analysed in this project. Here we describe the first RIKEN clone collection, which is one of the largest described for any organism. Analysis of these cDNAs extends known gene families and identifies new ones.     

Nuclear cataract caused by a lack of DNA degradation in the mouse eye lens

The eye lens is composed of fibre cells, which develop from the epithelial cells on the anterior surface of the lens. Differentiation into a lens fibre cell is accompanied by changes in cell shape, the expression of crystallins and the degradation of cellular organelles. The loss of organelles is believed to ensure the transparency of the lens, but the molecular mechanism behind this process is not known. Here we show that DLAD ('DNase II-like acid DNase', also called DNase IIbeta) is expressed in human and murine lens cells, and that mice deficient in the DLAD gene are incapable of degrading DNA during lens cell differentiation--the undigested DNA accumulates in the fibre cells. The DLAD-/- mice develop cataracts of the nucleus lentis, and their response to light on electroretinograms is severely reduced. These results indicate that DLAD is responsible for the degradation of nuclear DNA during lens cell differentiation, and that if DNA is left undigested in the lens, it causes cataracts of the nucleus lentis, blocking the light path.     

Functional architecture of an intracellular membrane t-SNARE

Lipid bilayer fusion is mediated by SNAREs (soluble N-ethylmaleimide-sensitive factor attachment protein receptors) located on the vesicle membrane (v-SNAREs) and the target membrane (t-SNAREs). The assembled v-SNARE/t-SNARE complex consists of a bundle of four helices, of which one is supplied by the v-SNARE and the other three by the t-SNARE. For t-SNAREs on the plasma membrane, the protein syntaxin supplies one helix and a SNAP-25 protein contributes the other two. Although there are numerous homologues of syntaxin on intracellular membranes, there are only two SNAP-25-related proteins in yeast, Sec9 and Spo20, both of which are localized to the plasma membrane and function in secretion and sporulation, respectively. What replaces SNAP-25 in t-SNAREs of intracellular membranes? Here we show that an intracellular t-SNARE is built from a 'heavy chain' homologous to syntaxin and two separate non-syntaxin 'light chains'. SNAP-25 may thus be the exception rather than the rule, having been derived from genes that encoded separate light chains that fused during evolution to produce a single gene encoding one protein with two helices.