Polo-like kinase 4 controls centriole duplication but does not directly regulate cytokinesis

Centrioles organize the centrosome, and accurate control of their number is critical for the maintenance of genomic integrity. Centrioles duplicate once per cell cycle, and duplication is coordinated by Polo-like kinase 4 (Plk4). We previously demonstrated that Plk4 accumulation is autoregulated by its own kinase activity. However, loss of heterozygosity of Plk4 in mouse embryonic fibroblasts has been proposed to cause cytokinesis failure as a primary event, leading to centrosome amplification and gross chromosomal abnormalities. Using targeted gene disruption, we show that human epithelial cells with one inactivated Plk4 allele undergo neither cytokinesis failure nor increase in centrosome amplification. Plk4 is shown to localize exclusively at the centrosome, with none in the spindle midbody. Substantial depletion of Plk4 by small interfering RNA leads to loss of centrioles and subsequent spindle defects that lead to a modest increase in the rate of cytokinesis failure. Therefore, Plk4 is a centriole-localized kinase that does not directly regulate cytokinesis.

Duplication, overlap, and fragmentation in government programs : hearing before the Committee on Governmental Affairs, United States Senate, One Hundred Fourth Congress, first session, June 7, 1995.

Shipping list no.: 96-0230-P.

Famous problems of elementary geometry; the duplication of the cube, the trisection of an angle; the quadrature of the circle;

Lettered on cover: Problems in geometry. Beman and Smith. 1922.

Factors governing the amount of duplication in content derived keys /

Vita.

Speed of sound duplication in hot-jet simulation

Mode of access: Internet.

Examination of patterns of career training levels for program and population duplication in Illinois /

"December 1972."

Gene duplication and hierarchical modularity in intracellular interaction networks

Networks of interactions evolve in many different domains. They tend to have topological characteristics in common, possibly due to common factors in the way the networks grow and develop. It has been recently suggested that one such common characteristic is the presence of a hierarchically modular organization. In this paper, we describe a new algorithm for the detection and quantification of hierarchical modularity, and demonstrate that the yeast protein-protein interaction network does have a hierarchically modular organization. We further show that such organization is evident in artificial networks produced by computational evolution using a gene duplication operator, but not in those developing via preferential attachment of new nodes to highly connected existing nodes. (C) 2004 Elsevier Ireland Ltd. All rights reserved.

Network topology and the evolution of dynamics in an artificial genetic regulatory network model created by whole genome duplication and divergence

Topological measures of large-scale complex networks are applied to a specific artificial regulatory network model created through a whole genome duplication and divergence mechanism. This class of networks share topological features with natural transcriptional regulatory networks. Specifically, these networks display scale-free and small-world topology and possess subgraph distributions similar to those of natural networks. Thus, the topologies inherent in natural networks may be in part due to their method of creation rather than being exclusively shaped by subsequent evolution under selection. The evolvability of the dynamics of these networks is also examined by evolving networks in simulation to obtain three simple types of output dynamics. The networks obtained from this process show a wide variety of topologies and numbers of genes indicating that it is relatively easy to evolve these classes of dynamics in this model. (c) 2006 Elsevier Ireland Ltd. All rights reserved.

Increased DNA Methylation at the AXIN1 Gene in a Monozygotic Twin from a Pair Discordant for a Caudal Duplication Anomaly

The AXIN1 gene has been implicated in caudal duplication anomalies. Its coding region was sequenced in both members of a monozygotic ( MZ) twin pair discordant for a caudal duplication anomaly, but no mutation was found. Using bisulfite sequencing, we examined methylation at the promoter region of the AXIN1 gene in these twins and in twin and age-matched singleton controls. Methylation of the promoter region in peripheral blood mononucleated cells was variable among individuals, including MZ pairs. In the MZ pair discordant for the caudal duplication, this region of the affected twin was significantly more methylated than that of the unaffected twin (), which was significantly more P < .0001 methylated than those of the controls (). We have confirmed that this CpG island does function as a promoter P = .02 in vitro and that its activity is inversely proportional to the extent of methylation. This finding raises the possibility that hypermethylation of the AXIN1 promoter, by mechanisms as yet undetermined, is associated with the malformation. This case may be paradigmatic for some cases of MZ discordance.

Targeted sequencing for high-resolution evolutionary analyses following genome duplication in salmonid fish : Proof of concept for key components of the insulin-like growth factor axis

Acknowledgements This study was funded by a Natural Environment Research Council grant (NERC, project code: NBAF704). FML is funded by a NERC Doctoral Training Grant (Project Reference: NE/L50175X/1). RLS was an undergraduate student at the University of Aberdeen and benefitted from financial support from the School of Biological Sciences. DJM is indebted to Dr. Steven Weiss (University of Graz, Austria), Dr. Takashi Yada (National Research Institute of Fisheries Science, Japan), Dr. Robert Devlin (Fisheries and Oceans Canada, Canada), Prof. Samuel Martin (University of Aberdeen, UK), Mr. Neil Lincoln (Environment Agency, UK) and Prof. Colin Adams/Mr. Stuart Wilson (University of Glasgow, UK) for providing salmonid material or assisting with its sampling. We are grateful to staff at the Centre for Genomics Research (University of Liverpool, UK) (i.e. NERC Biomolecular Analysis Facility – Liverpool; NBAF-Liverpool) for performing sequence capture/Illumina sequencing and providing us with details on associated methods that were incorporated into the manuscript. Finally, we are grateful to the organizers of the Society of Experimental Biology Satellite meeting 'Genome-powered perspectives in integrative physiology and evolutionary biology' (held in Prague, July 2015) for inviting us to contribute to this special edition of Marine Genomics and hosting a really stimulating meeting.

Arterial entrapment syndrome in the cubital fossa: a rare cause of acute stress-related arterial thrombosis in a patient with brachial artery duplication

Arterial entrapment syndrome (AES) at elbow level is very rare and to our knowledge no case of AES by lacertus fibrosus in the cubital fossa in presence of brachial artery duplication has been described to date. We describe a rare case of acute arterial thrombosis of one of two brachial arteries highlighted in the cubital fossa which developed after strenuous right elbow flexor muscle activity and hyper-extensions presumably related to AES by lacertus fibrosus at elbow level. A 43-year-old right-handed woman, experienced paleness, coldness and numbness of the right hand, after 8 consecutive hours of gardening. As she worked, her ipsilateral flexor elbow muscles remained in prolonged and inappropriate tension. Clinical examination evidenced the absence of radial artery pulse in the wrist and mild hypothermia in the second and third finger. During surgical exploration two anastomosed brachial arteries were detected in the cubital fossa under the lacertus fibrosus. The lateral superficial brachial artery was occluded. Intraoperative arteriography evidenced brachial artery duplication at the third superior of the arm and normal vascular pattern at the forearm level. In cases of unexplained atypical intermittent upper extremity claudication or acute ischemic symptoms an AES should always be ruled out, particularly when symptoms are exacerbated by strenuous upper extremity activity or when upper limb muscular hypertrophy is evident. In these cases a thorough dynamic clinical and instrumental examination is mandatory to confirm a diagnosis of AES and to avoid possible future ischemic complications.

Large national series of patients with Xq28 duplication involving MECP2: Delineation of brain MRI abnormalities in 30 affected patients.

Xq28 duplications encompassing MECP2 have been described in male patients with a severe neurodevelopmental disorder associated with hypotonia and spasticity, severe learning disability, stereotyped movements, and recurrent pulmonary infections. We report on standardized brain magnetic resonance imaging (MRI) data of 30 affected patients carrying an Xq28 duplication involving MECP2 of various sizes (228 kb to 11.7 Mb). The aim of this study was to seek recurrent malformations and attempt to determine whether variations in imaging features could be explained by differences in the size of the duplications. We showed that 93% of patients had brain MRI abnormalities such as corpus callosum abnormalities (n = 20), reduced volume of the white matter (WM) (n = 12), ventricular dilatation (n = 9), abnormal increased hyperintensities on T2-weighted images involving posterior periventricular WM (n = 6), and vermis hypoplasia (n = 5). The occipitofrontal circumference varied considerably between >+2SD in five patients and <-2SD in four patients. Among the nine patients with dilatation of the lateral ventricles, six had a duplication involving L1CAM. The only patient harboring bilateral posterior subependymal nodular heterotopia also carried an FLNA gene duplication. We could not demonstrate a correlation between periventricular WM hyperintensities/delayed myelination and duplication of the IKBKG gene. We thus conclude that patients with an Xq28 duplication involving MECP2 share some similar but non-specific brain abnormalities. These imaging features, therefore, could not constitute a diagnostic clue. The genotype-phenotype correlation failed to demonstrate a relationship between the presence of nodular heterotopia, ventricular dilatation, WM abnormalities, and the presence of FLNA, L1CAM, or IKBKG, respectively, in the duplicated segment.

Complete Urethral Duplication in Children: A Case Report

Introduction: Urethral duplication (UD) is a rare congenital anomaly with multiple anatomical variants. Case Presentation: In this article we present a four year-old child with complete UD. The patient was admitted for hypospadias repair, in evaluation we found type IIA1 UD according to Effmann classification. Patient underwent hypospadias repair saving complete UD. Conclusions: After one year follow-up he has normal and continent urination.

Leaf-, Panel- And Latex-expressed Sequenced Tags From The Rubber Tree (hevea Brasiliensis) Under Cold-stressed And Suboptimal Growing Conditions: The Development Of Gene-targeted Functional Markers For Stress Response.

Hevea brasiliensis is a native species of the Amazon Basin of South America and the primary source of natural rubber worldwide. Due to the occurrence of South American Leaf Blight disease in this area, rubber plantations have been extended to suboptimal regions. Rubber tree breeding is time-consuming and expensive, but molecular markers can serve as a tool for early evaluation, thus reducing time and costs. In this work, we constructed six different cDNA libraries with the aim of developing gene-targeted molecular markers for the rubber tree. A total of 8,263 reads were assembled, generating 5,025 unigenes that were analyzed; 912 expressed sequence tags (ESTs) represented new transcripts, and two sequences were highly up-regulated by cold stress. These unigenes were scanned for microsatellite (SSR) regions and single nucleotide polymorphisms (SNPs). In total, 169 novel EST-SSR markers were developed; 138 loci were polymorphic in the rubber tree, and 98 % presented transferability to six other Hevea species. Locus duplication was observed in H. brasiliensis and other species. Additionally, 43 SNP markers in 13 sequences that showed similarity to proteins involved in stress response, latex biosynthesis and developmental processes were characterized. cDNA libraries are a rich source of SSR and SNP markers and enable the identification of new transcripts. The new markers developed here will be a valuable resource for linkage mapping, QTL identification and other studies in the rubber tree and can also be used to evaluate the genetic variability of other Hevea species, which are valuable assets in rubber tree breeding.