Nras loss induces metastatic conversion of Rb1-deficient neuroendocrine thyroid tumor

Mutations in the gene encoding the retinoblastoma tumor suppressor predispose humans and mice to tumor development. Here we have assessed the effect of Nras loss on tumor development in Rb1 heterozygous mice. Loss of one or two Nras alleles is shown to significantly reduce the severity of pituitary tumors arising in Rb1(+/-) animals by enhancing their differentiation. By contrast, C-cell thyroid adenomas occurring in Rb1(+/-) mice progress to metastatic medullary carcinomas after loss of Nras. In Rb1(+/-)Nras(+/-) animals, distant medullary thyroid carcinoma metastases are associated with loss of the remaining wild-type Nras allele. Loss of Nras in Rb1-deficient C cells results in elevated Ras homolog family A (RhoA) activity, and this is causally linked to the invasiveness and metastatic behavior of these cells. These findings suggest that the loss of the proto-oncogene Nras in certain cellular contexts can promote malignant tumor progression.     

A negative element in SMN2 exon 7 inhibits splicing in spinal muscular atrophy

Spinal muscular atrophy (SMA) is a relatively common neurodegenerative disease caused by homozygous loss of the survival motor neuron 1 (SMN1) gene. Humans possess a linked, nearly identical gene, SMN2, which produces a functional SMN protein but at levels insufficient to compensate for loss of SMN1 (refs. 1,2). A C/T transition at position +6 in exon 7 is all that differentiates the two genes, but this is sufficient to prevent efficient exon 7 splicing in SMN2 (refs. 2,3). Here we show that the C/T transition functions not to disrupt an exonic splicing enhancer (ESE) in SMN1 (ref. 4), as previously suggested, but rather to create an exonic splicing silencer (ESS) in SMN2. We show that this ESS functions as a binding site for a known repressor protein, hnRNP A1, which binds to SMN2 but not SMN1 exon 7 RNA. We establish the physiological importance of these results by using small interfering RNAs to reduce hnRNP A protein levels in living cells and show that this results in efficient SMN2 exon 7 splicing. Our findings not only define a new mechanism underlying the inefficient splicing of SMN2 exon 7 but also illustrate more generally the remarkable sensitivity and precision that characterizes control of mRNA splicing.     

The axon reflex sweating produced by potassium and sodium cyanides

Zusammenfassung Subkutane Einspritzung von Kalium- oder Natriumzyanid in die Zehenballen der Katze führt über einen Axonreflex zu merklichem Schwitzen. Dieser Effekt von Kaliumzyanid wird durch Procain und Atropin gehemmt, nicht aber durch Hexamethonium. Auch beim Menschen ruft intrakutan eingeführtes Natriumzyanid eine entsprechende Schweissabsonderung hervor.     

Photocatalyst releasing hydrogen from water

Direct splitting of water using a particulate photocatalyst would be a good way to produce clean and recyclable hydrogen on a large scale, and in the past 30 years various photocatalysts have been found that function under visible light. Here we describe an advance in the catalysis of the overall splitting of water under visible light: the new catalyst is a solid solution of gallium and zinc nitrogen oxide, (Ga(1-x)Zn(x))(N(1-x)O(x)), modified with nanoparticles of a mixed oxide of rhodium and chromium. The mixture functions as a promising and efficient photocatalyst in promoting the evolution of hydrogen gas.     

Effects of Au nanoparticle addition to hole transfer layer in organic solar cells based on copper naphthalocyanine and fullerene

Organic solar cells based on copper naphthalocyanine(CuNc) and fullerene(C60) were fabricated, and their photovoltaic properties were investigated. C60 and CuNc were used as n-type and p-type semiconductors, respectively. In addition, the effect of Au nanoparticle addition on a hole transfer layer was investigated, and the power conversion efficiency of the devices was improved after blending the Au nanoparticles into the hole transport layer. Nanostructures of Au nanoparticles were investigated by transmission electron microscopy and X-ray diffraction. Energy levels of molecules were calculated by molecular orbital calculations, and the nanostructure and electronic properties were discussed.& 2014 Chinese Materials Research Society. Production and hosting by Elsevier B.V. All rights reserved.     

产甲烷阶段季铵化合物的厌氧生物降解性研究(英文)

基于厌氧序批式测试系统,研究了一组季铵化合物的最终生物降解性和对生物气产生过程的毒性效果.四个测试物中每个化合物均带有四个相同的烷基,通式为R4N+Br-(TEAB,TPAB,TOAB和TODAB分别对应R=C2,C5,C8,C18,).测试物的矿化程度被用来评估其最终厌氧生物降解性;对碳源D-葡萄糖代谢过程的毒性可以利用测试物对生物气生成过程的抑制效果来指示.研究结果表明:带有偶碳数烷基链的季铵化合物,即TEAB、TOAB和TODAB在20 mg/L(以C计)能够被很容易地降解为CO2和CH4,它们对生物气生成过程的毒性随着所带烷基链长的增长而减小.测试物中带有最长碳链的TODAB,即使碳浓度提高到100 mg/L也可以顺利降解;并且在200 mg/L的高浓度条件下也没有发现其对代谢过程的毒性证据.相反,带有奇数碳链的TPAB很难被厌氧生物降解,而且在所有测试物中显示出最强的厌氧毒性,200 mg/L时的生物气抑制率高达69%.     

Haploinsufficiency of NSD1 causes Sotos syndrome

We isolated NSD1 from the 5q35 breakpoint in an individual with Sotos syndrome harboring a chromosomal translocation. We identified 1 nonsense, 3 frameshift and 20 submicroscopic deletion mutations of NSD1 among 42 individuals with sporadic cases of Sotos syndrome. The results indicate that haploinsufficiency of NSD1 is the major cause of Sotos syndrome.     

Cyclic electron flow around photosystem I is essential for photosynthesis

Photosynthesis provides at least two routes through which light energy can be used to generate a proton gradient across the thylakoid membrane of chloroplasts, which is subsequently used to synthesize ATP. In the first route, electrons released from water in photosystem II (PSII) are eventually transferred to NADP+ by way of photosystem I (PSI). This linear electron flow is driven by two photochemical reactions that function in series. The cytochrome b6f complex mediates electron transport between the two photosystems and generates the proton gradient (DeltapH). In the second route, driven solely by PSI, electrons can be recycled from either reduced ferredoxin or NADPH to plastoquinone, and subsequently to the cytochrome b6f complex. Such cyclic flow generates DeltapH and thus ATP without the accumulation of reduced species. Whereas linear flow from water to NADP+ is commonly used to explain the function of the light-dependent reactions of photosynthesis, the role of cyclic flow is less clear. In higher plants cyclic flow consists of two partially redundant pathways. Here we have constructed mutants in Arabidopsis thaliana in which both PSI cyclic pathways are impaired, and present evidence that cyclic flow is essential for efficient photosynthesis.     

Development of the Driving Simulation System MOVIC-T4 and Its Validation Using Field Driving Data

Underground urban expressways are a possibility for solving many existing transportation-related problems, such as traffic congestion in high density areas and the division of neighborhoods due to elevated roadways. However, they may also pose high risks regarding traffic safety. Therefore, it is important for a pre-analysis of traffic safety to be made. This paper describes recent efforts to develop a driving simulation system, MOVIC-T4, for traffic safety analysis of underground urban expressways. In order to develop a small portable simulator, a small-sized motion-base with two-degrees-of-freedom is used to duplicate accel-eration cueing together with a head-mounted-display (HMD) for the visual system. An overview of this sys-tem is given and the reliability of driving data obtained from the experiments using MOVIC-T4 is discussed through a validation study using field driving data. The results of validation indicate that the perceived speed, distance headway, and physiological data in the simulator show the almost same trend as that in the real world, but larger decelerations tend to be produced in the simulator.     

Thyrotrophin in the pars tuberalis triggers photoperiodic response

Molecular mechanisms regulating animal seasonal breeding in response to changing photoperiod are not well understood. Rapid induction of gene expression of thyroid-hormone-activating enzyme (type 2 deiodinase, DIO2) in the mediobasal hypothalamus (MBH) of the Japanese quail (Coturnix japonica) is the earliest event yet recorded in the photoperiodic signal transduction pathway. Here we show cascades of gene expression in the quail MBH associated with the initiation of photoinduced secretion of luteinizing hormone. We identified two waves of gene expression. The first was initiated about 14 h after dawn of the first long day and included increased thyrotrophin (TSH) beta-subunit expression in the pars tuberalis; the second occurred approximately 4 h later and included increased expression of DIO2. Intracerebroventricular (ICV) administration of TSH to short-day quail stimulated gonadal growth and expression of DIO2 which was shown to be mediated through a TSH receptor-cyclic AMP (cAMP) signalling pathway. Increased TSH in the pars tuberalis therefore seems to trigger long-day photoinduced seasonal breeding.