The coiled-coil domain containing protein CCDC40 is essential for motile cilia function and left-right axis formation

Primary ciliary dyskinesia (PCD) is a genetically heterogeneous autosomal recessive disorder characterized by recurrent infections of the respiratory tract associated with the abnormal function of motile cilia. Approximately half of individuals with PCD also have alterations in the left-right organization of their internal organ positioning, including situs inversus and situs ambiguous (Kartagener's syndrome). Here, we identify an uncharacterized coiled-coil domain containing a protein, CCDC40, essential for correct left-right patterning in mouse, zebrafish and human. In mouse and zebrafish, Ccdc40 is expressed in tissues that contain motile cilia, and mutations in Ccdc40 result in cilia with reduced ranges of motility. We further show that CCDC40 mutations in humans result in a variant of PCD characterized by misplacement of the central pair of microtubules and defective assembly of inner dynein arms and dynein regulatory complexes. CCDC40 localizes to motile cilia and the apical cytoplasm and is required for axonemal recruitment of CCDC39, disruption of which underlies a similar variant of PCD.     

萃取动力学分析法的研究和应用Ⅵ.非催化法测定Ce(Ⅳ)

利用Ce(Ⅳ)在2mol/LHCl 介质中氧化二苯硫腙褪色的慢反应,用萃取平衡控制反应时间和水相中二苯硫腙的浓度,建立了非催化动力学分析法测定Ce(Ⅳ)的新方法。反应速度的检测是在620nm下测定反应前后CCl_4相中二苯硫腙吸光度的变化。方法的检测限为5.0×10~(-7) gCe(Ⅳ)·ml~(-1) ,线性范围为0. 5-5μgCe(Ⅳ)·ml~(-1)。对干扰严重的金属离子 Ag~+、Au~(3+)、Cu~(2+)、Hg~(2+)等可在 pH4-6条件下,用二苯硫腙的四氯化碳溶液萃取除去。将方法用于测定合成水样中Ce(Ⅳ),结果满意。     

A novel biochemical systematic technique for herpetology based on epidermal keratin

Summary Using green geckos (Phelsuma) the molecular weights and isoelectric points of S-carboxymethylated keratin monomers from fresh and preserved reptile epidermis were investigated. Isoelectric focussing reveals that several of the circa 35 components differ between genera, species and races and that the relative similarity of the SCMK pattern is directly related to evolutionary similarity and is of considerable taxonomic value.We would like to thank the SRC (grant A/8799.9 to R.S. Th.) and the Department of Zoology, Aberdeen for funding this research and Dr Alan Knox for his advice and assistance at the inception of this project. R.S. Th. would like to thank the Bonhote fund, Carnegie Trust and the Joint Research Committee of Aberdeen University for travel expenses related to this research and the Reptile and Amphibian section of the BMNH for the loan of specimens. M. G. would like to thank J.M. Gillespie for communications on keratin biochemistry and Dr Charteris (BDH) for a sample of their molecular weight markers prior to it being marketed.     

Stimulation of locomotor activity of genetically obese mice by amphetamine

Zusammenfassung Die motorische Aktivität von genetish obesen (ob/ob) und diabetischen (db/db) Mäusen wurde durchd-Amphetamin stärker gesteigert als bei normalen Mäusen, wobei das Regulationszentrum für die motorische Aktivität intakt zu sein scheint.     

A Branch and Bound-Based Algorithm for the Weak Linear Bilevel Programming Problems

Most real-world optimization problems are hierarchical involving non-cooperative objectives. Many of these problems can be formulated in terms of the first (upper level) objective function being minimized over the solution set mapping of the second (lower level) optimization problem. Often the upper level decision maker is risk-averse. The resulting class of problem is named weak bilevel programming problem. This paper presents a new algorithm which embeds a penalty function method into a branch and bound algorithm to deal with a weak linear bilevel programming problem. An example illustrates the feasibility of the proposed algorithm.     

Trans allele methylation and paramutation-like effects in mice

In mammals, imprinted genes have parent-of-origin-specific patterns of DNA methylation that cause allele-specific expression. At Rasgrf1 (encoding RAS protein-specific guanine nucleotide-releasing factor 1), a repeated DNA element is needed to establish methylation and expression of the active paternal allele. At Igf2r (encoding insulin-like growth factor 2 receptor), a sequence called region 2 is needed for methylation of the active maternal allele. Here we show that replacing the Rasgrf1 repeats on the paternal allele with region 2 allows both methylation and expression of the paternal copy of Rasgrf1, indicating that sequences that control methylation can function ectopically. Paternal transmission of the mutated allele also induced methylation and expression in trans of the normally unmethylated and silent wild-type maternal allele. Once activated, the wild-type maternal Rasgrf1 allele maintained its activated state in the next generation independently of the paternal allele. These results recapitulate in mice several features in common with paramutation described in plants.     

A microbial symbiosis factor prevents intestinal inflammatory disease

Humans are colonized by multitudes of commensal organisms representing members of five of the six kingdoms of life; however, our gastrointestinal tract provides residence to both beneficial and potentially pathogenic microorganisms. Imbalances in the composition of the bacterial microbiota, known as dysbiosis, are postulated to be a major factor in human disorders such as inflammatory bowel disease. We report here that the prominent human symbiont Bacteroides fragilis protects animals from experimental colitis induced by Helicobacter hepaticus, a commensal bacterium with pathogenic potential. This beneficial activity requires a single microbial molecule (polysaccharide A, PSA). In animals harbouring B. fragilis not expressing PSA, H. hepaticus colonization leads to disease and pro-inflammatory cytokine production in colonic tissues. Purified PSA administered to animals is required to suppress pro-inflammatory interleukin-17 production by intestinal immune cells and also inhibits in vitro reactions in cell cultures. Furthermore, PSA protects from inflammatory disease through a functional requirement for interleukin-10-producing CD4+ T cells. These results show that molecules of the bacterial microbiota can mediate the critical balance between health and disease. Harnessing the immunomodulatory capacity of symbiosis factors such as PSA might potentially provide therapeutics for human inflammatory disorders on the basis of entirely novel biological principles.     

基于转录组高通量测序分析白光对杜仲愈伤组织中绿原酸含量的影响

利用Illumina HiSeq 2500平台对光暗培养的杜仲愈伤组织进行了转录组高通量测序,利用BLAST软件进行差异表达基因的功能注释和富集分析,就白光(光强为12 000 lux,16 h 光照,8 h 黑暗)对杜仲愈伤组织中绿原酸含量的影响进行了研究.结果表明:通过Trinity软件合并组装后共获得62 030个Unigenes,通过BLASTX比对,共获得25 417(40.98%)个有注释信息的Unigenes.通过对KEGG通路进行深入分析表明,白光(光强为12 000 lux,16 h 光照,8 h 黑暗)培养杜仲愈伤组织18 d,与绿原酸合成相关的3种酶基因上调表达,它们分别为苯丙氨酸解氨酶(EC 4.3.1.24,phenylalanine ammonia-lyase,PAL)、肉桂酸-4-羟基化酶(EC 1.14.13.11,trans-cinnamate 4-monooxygenase,C4H)、奎宁酸羟基肉桂酰转移酶(EC 2.3.1.133,Shikimate o-hydroxyl-cinnamoyltransferase,HCT).由此推断,白光能促进杜仲愈伤组织中绿原酸的积累.研究结果为获取高产绿原酸资源和杜仲遗传分析提供有价值的资料.     

Hageman factor activation and tight junction disruption in mice challenged with attenuated endotoxin

Summary Endotoxin treated with chromium chloride is less toxic to mice than the parent molecule, but can disrupt intestinal permeability barriers and has an enhanced ability to activate Hageman factor.We wish to thank Drs M.W. Brightman and T.S. Reese from the Department of Neurocytology, National Institutes of Health for the use of their Balzers freeze-fracture instrument.     

Agreement in endpoints from circadian rhythmometry on healthy human beings living on different continents

Zusammenfassung Circadiane Akrophasen — Gipfel der ungefähren 24-h-Periodik — von Blut- und Harnkortikosteroiden, Kalium im Harn, Körpertemperatur, Pulsrate und 2-min-Schätzung wurden mittels elektronischer Anpassung einer Kosinusfunktion vermöge der Methode der kleinsten Quadrate bestimmt. Solche Charakteristika circadianer Rhythmen empfehlen sich als Referenzstandarde dem Mediziner und Biologen durch ihre zufriedenstellende übereinstimmung in Daten von Untersuchungen auf verschiedenen Kontinenten mit zum Teil unterschiedlichen Methoden.