Mutations in the PCNA-binding domain of CDKN1C cause IMAGe syndrome

IMAGe syndrome (intrauterine growth restriction, metaphyseal dysplasia, adrenal hypoplasia congenita and genital anomalies) is an undergrowth developmental disorder with life-threatening consequences. An identity-by-descent analysis in a family with IMAGe syndrome identified a 17.2-Mb locus on chromosome 11p15 that segregated in the affected family members. Targeted exon array capture of the disease locus, followed by high-throughput genomic sequencing and validation by dideoxy sequencing, identified missense mutations in the imprinted gene CDKN1C (also known as P57KIP2) in two familial and four unrelated patients. A familial analysis showed an imprinted mode of inheritance in which only maternal transmission of the mutation resulted in IMAGe syndrome. CDKN1C inhibits cell-cycle progression, and we found that targeted expression of IMAGe-associated CDKN1C mutations in Drosophila caused severe eye growth defects compared to wild-type CDKN1C, suggesting a gain-of-function mechanism. All IMAGe-associated mutations clustered in the PCNA-binding domain of CDKN1C and resulted in loss of PCNA binding, distinguishing them from the mutations of CDKN1C that cause Beckwith-Wiedemann syndrome, an overgrowth syndrome.     

等离子喷涂铁基非晶/晶体复合涂层的工艺–结构–性能关系

本研究试图通过优化等离子喷涂参数来开发一种Fe基非晶/晶体涂层,该涂层主要成分来自一种贫乏的铁基合金（Fe_92.6C_3.5P_1.4Si₂Mn_0.5）。这种合金是钢铁厂高炉产出的生铁剩余废料。为了经济有效地重新利用这种残留物,这种合金在合成时对成分进行了最少的修改。同时,本研究还探讨了涂层的结构、机械、腐蚀和磨损性能对喷涂参数（等离子功率、主气体流速、送粉速度和间隔距离）的依赖性。X射线衍射表明,在最优的喷涂参数下沉积的涂层存在无定形/晶体相。在较低等离子功率和最高气体流速下沉积的涂层表现出更好的密度、硬度和耐磨性。所有涂层都表现出良好的耐腐蚀性（腐蚀环境:3.5wt% NaCl 溶液）。机械、磨损和摩擦学研究表明,单一的工艺参数优化无法提供良好的涂层性能;相反,所有工艺参数在优化涂层性能都具有独一无二的作用,它们主要通过控制飞行中的颗粒温度和速度分布,以及熔滴撞击基材之前的冷却模式来控制涂层性能。     

Preferential cytotoxicity on tumor cells by caffeic acid phenethyl ester isolated from propolis

The honeybee hive product, propolis, is a folk medicine employed for treating various ailments. Many important pharmaceutical properties have been ascribed to propolis, including anti-inflammatory, antiviral, immunostimulatory and carcinostatic activities. Propolis extracts have provided an active component identified as caffeic acid phenethyl ester (CAPE), which was readily prepared in one step. Differential cytotoxicity has been observed in normal rat/human versus transformed rat/human melanoma and breast carcinoma cell lines in the presence of CAPE.     

Variance to mean ratio and the spatial distribution of animals

Summary Biological and statistical aspects of the application of variance to mean ratio to describe spatial distribution of animals are discussed. It is shown that the parameterb inTaylor's power laws ²=a m ^b shows intra-specific variation depending on the distribution of the constituent units of the population.a andb are only parameters of a very empirical way of describing the relation between variance and mean, which itself is an indicator for spatial distribution. Hence,a andb depend on the distribution behaviour of the animals, and not vice versa.Acknowledgments: The work was developed whilst I was at the Department of Entomology, University of Nairobi. I am grateful to ProfessorT. R. Odhiambo for his interest. I thank the referee for comments.     

Distinct mitochondrial retrograde signals control the G1-S cell cycle checkpoint

During electron transport, the mitochondrion generates ATP and reactive oxygen species (ROS), a group of partially reduced and highly reactive metabolites of oxygen. In this in vivo genetic analysis in Drosophila melanogaster, we establish that disruption of complex I of the mitochondrial electron transport chain specifically retards the cell cycle during the G1-S transition. The mechanism involves a specific signaling cascade initiated by ROS and transduced by ASK-1, JNK, FOXO and the Drosophila p27 homolog, Dacapo. On the basis of our data combined with previous analyses of the system, we conclude that mitochondrial dysfunction activates at least two retrograde signals to specifically enforce a G1-S cell cycle checkpoint. One such signal involves an increase in AMP production and downregulation of cyclin E protein; another independent pathway involves increased ROS and upregulation of Dacapo. Thus, our results indicate that the mitochondrion can use AMP and ROS at sublethal concentrations as independent signaling molecules to modulate cell cycle progression.