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As key regulators of mitotic chromosome segregation, the Aurora family of serine/threonine kinases play an important role in cell division. Abnormalities in Aurora kinases have been strongly linked with cancer, which has lead to the recent development of new classes of anti-cancer drugs that specifically target the ATP-binding domain of these kinases. From an evolutionary perspective, the species distribution of the Aurora kinase family is complex. Mammals uniquely have three Aurora kinases, Aurora-A, Aurora-B, and Aurora-C, while for other metazoans, including the frog, fruitfly and nematode, only Aurora-A and Aurora-B kinases are known. The fungi have a single Aurora-like homolog. Based on the tacit assumption of orthology to human counterparts, model organism studies have been central to the functional characterization of Aurora kinases. However, the ortholog and paralog relationships of these kinases across various species have not been rigorously examined. Here, we present comprehensive evolutionary analyses of the Aurora kinase family.
Phylogenetic trees suggest that all three vertebrate Auroras evolved from a single urochordate ancestor. Specifically, Aurora-A is an orthologous lineage in cold-blooded vertebrates and mammals, while structurally similar Aurora-B and Aurora-C evolved more recently in mammals from a duplication of an ancestral Aurora-B/C gene found in cold-blooded vertebrates. All so-called Aurora-A and Aurora-B kinases of non-chordates are ancestral to the clade of chordate Auroras and, therefore, are not strictly orthologous to vertebrate counterparts. Comparisons of human Aurora-B and Aurora-C sequences to the resolved 3D structure of human Aurora-A lends further support to the evolutionary scenario that vertebrate Aurora-B and Aurora-C are closely related paralogs. Of the 26 residues lining the ATP-binding active site, only three were variant and all were specific to Aurora-A.
In this study, we found that invertebrate Aurora-A and Aurora-B kinases are highly divergent protein families from their chordate counterparts. Furthermore, while the Aurora-A family is ubiquitous among all vertebrates, the Aurora-B and Aurora-C families in humans arose from a gene duplication event in mammals. These findings show the importance of understanding evolutionary relationships in the interpretation and transference of knowledge from studies of model organism systems to human cellular biology. In addition, given the important role of Aurora kinases in cancer, evolutionary analysis and comparisons of ATP-binding domains suggest a rationale for designing dual action anti-tumor drugs that inhibit both Aurora-B and Aurora-C kinases.
The Auroras are a conserved family of serine/threonine kinases which have essential functions in cell division [1,2]. In mitosis, Aurora kinases are required for chromosome segregation, condensation and orientation in the metaphase plate, spindle assembly, and the completion of cytokinesis.
Model organism studies have played a pivotal role in functional characterization of Aurora kinases. Aurora kinases were first identified as mutant alleles in Drosophila melanogaster (fruitfly) that caused defective spindle-pole formation [3]. Subsequently, Drosophila was found to have a second Aurora homolog [4], and the nematode, Caenorhabditis elegans, similarly has two Aurora-like genes [5,6]. The fungi, Saccharomyces cerevisiae and Schizosaccharomyces pombe, have a single Aurora, known as increase-in-ploidy 1 (Ipl1) [7] and Aurora-related kinase 1 (Ark1) [8], respectively. Among cold-blooded vertebrates, Aurora kinases have been most widely studied in the frog, Xenopus laevis, which has two kinases; Aurora-A and Aurora-B [9,10]. More recently discovered is a third Aurora kinase called Aurora-C in rodents and humans [11].
The Aurora kinases are mitotic kinases that generally associate with chromosomes, often in complexes with other proteins, and interact with cytoskeletal components in cell division. The three mammalian Aurora kinases appear at specific locations during mitosis. Aurora-A, the "polar kinase", primarily associates with the separating centrosomes while Aurora-B, the "equatorial kinase", is a chromosomal passenger protein [1]. The least studied Aurora kinase, Aurora-C, appears to be localized to the centrosome from anaphase to telophase and is highly expressed in the testis [11,12].
Recent studies indicate that all three Aurora kinases have strong associations with cancer. Aurora-A has been mapped to a region in the human chromosome (20q13.2-13.3) that is amplified in cancer cell lines and primary tumors [13,14]. Transfected mouse cell lines with Aurora-A have been shown to cause tumors when injected into nude mice [14,15] and a polymorphic variant (amino acid substitution Phe31Ile) has been associated with human colon tumors [16]. Expression levels of Aurora-B [17] and Aurora-C [12] were elevated in several cancer cell lines relative to normal fibroblasts. Aurora-C is located on chromosome 19q13.2 to 13.4, a region associated with loss of heterozygosity in ovarian cancer [18] and pancreatic carcinomas [19]. Thus, the inhibition of one or more Aurora kinases might be a novel chemotherapeutic strategy against cancer [20]. Recently, several reports by research groups in pharmaceutical and biotechnology companies describe small molecules that target the ATP-binding domain of Aurora kinases, and have effects in human tumor cell lines [21-23].
Despite the importance of model organisms in understanding Aurora kinase function, the evolutionary relationships among these variants are unclear. Two previous phylogenetic analyses of Aurora kinases were incomplete because the contemporary complement of Aurora kinases was unavailable [4] or certain family members, namely the Aurora-C kinases, were excluded [1]. Here, we present an evolutionary analysis of all known Aurora kinases. We show that vertebrate Aurora kinases evolved through a series of gene duplication events from a chordate ancestor, and that they are highly distinct from invertebrate homologs. Moreover, the recent divergence, thus high level of sequence similarity, of human Aurora-B and Aurora-C suggests a novel anti-cancer strategy which might simultaneously target the ATP-binding domains of this kinase pair with dual action inhibitors.
Results and discussion
Aurora Evolution in Chordates
In order to construct a comprehensive phylogenetic tree, GenBank was searched for all possible Aurora kinases. In addition to previously published Aurora kinase sequences, further chordate and urochordate Aurora homologs were found by using mammalian Aurora-A, Aurora-B and Aurora-C protein sequences as queries in BLASTP or TBLASTN [24] searches of the genomes of the pufferfish, Takifugu rubripes [25], the zebrafish, Danio rerio [26], and the ascidian, Ciona intestinalis [27].
Multiple sequence alignments show that the Aurora kinase family is highly conserved among species (Fig. 1). Pairwise sequence comparisons estimate that the mean proportion of similar amino acids (based on the Blosum62 matrix) is much higher among all the different families of Aurora-A, Aurora-B and Aurora-C of vertebrates (0.84 ± 0.5) than within the same family (Aurora-A or Aurora-B) between vertebrates and invertebrates species (0.69 ± 0.3 for both families). This would suggest a recent evolutionary radiation of Aurora families within vertebrates.
Figure 1. Multiple sequence alignment of representative Aurora-A (AurA), Aurora-B (AurB), and Aurora-C (AurC) kinases, and their homologs (Air1, Air2, ARK1 and Ipl1). N-terminal regions which are species-specific and could not be accurately aligned are excluded, although the numbering of residues begins at the starting amino acid for that particular peptide. Progressive darker shading indicates conservation of amino acid residues in 60%, 80% and 100% of the sequences, respectively. Dark line at the top of the sequence blocks indicates those regions used in the phylogenetic analyses (Also see 1 and 2). Species include Homo sapiens (hosa), Mus musculus (mus), Danio rerio (dare), Takifugu rubripes (taru), Xenopus laevis (xela), Ciona intestinalis (ciin), Drosophila melanogaster (drme), Caenorhabditis elegans (cael), Saccharomyces cerevisiae (sace) and Schizosaccharomyces pombe (scpo). The program CLUSTALW [41] was used to constructed the initial alignment which was subsequently refined manually.
Additional File 1. Multiple sequence alignment of edited Aurora and Plk4 kinases used to produce the phylogeny shown in Fig. 2.
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Additional File 2. Accession numbers (gi), Locus link Ids (LID) or genome predicted protein Ids for Aurora and PLK kinases as labelled in the Supplementary Data multiple sequence alignment file S1.
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Phylogenetic trees constructed using four methodologies, all rooted using polo-like kinases type 4 (PLK4), show that all vertebrate Auroras form a clade distinct from those of invertebrates (Fig. 2). The phylogenetic tree constructed by the neighbour-joining distance method shows moderate boot-strap support (67%) for the evolution of all vertebrate Auroras from a urochordate ancestor, represented by the ascidian, C. intestinalis. The use of alternative kinase families, other than PLK4, to root the tree did not alter the internal topology of the Aurora clade. Although its genome sequence is incomplete, C. intestinalis likely has only a single Aurora homolog since other probable kinase open reading frames associated with the next top five BLASTP [24] hits did not cluster with Auroras from other species in phylogenetic trees.
Figure 2. Phylogenetic tree of Aurora-A, Aurora-B, and Aurora-C kinases rooted by PLK4 kinases. Major organism groups (with colours, fonts) are mammals (red, bold italic), cold-blooded vertebrates (deep blue, italic), urochordates (orange, italic), invertebrates, (purple, italic), plants (green, italic), fungi (black, italic) and protists (light blue, italic). "Original" indicates the first Aurora identified from Drosophila melanogaster [3]. Plant sequences are identified by their Genbank accession number. Stacks of numbers show, in descending order, the percent occurrence of nodes in greater than 50% of 1000 bootstrap replicates of neighbor joining (plain text) and maximum parsimony (italicized text) analyses or greater than 50% of 10000 quartet puzzling steps of maximum likelihood analysis (in curved parentheses) or Bayesian posterior probability (only 0.90 or greater, in square parentheses). Asterisks ("*") indicate those nodes supported 70% or greater by the first three tree-building methods and 0.90 Bayesian posterior probability. Nodes with one or two values less than 50% have dashes ("-") while values less than 50% are unmarked. Scale bar represents 0.1 expected amino acid residue substitutions per site.
Among true vertebrates, our phylogenetic tree shows that the Aurora kinases underwent two major gene duplication events. The first split in cold-blooded vertebrates lead to the formation of two Aurora subfamilies. One branch encompasses all known vertebrate Aurora-A sequences in a single orthologous lineage that includes fishes, amphibians and mammals. This family includes previously identified Aurora-A kinases in Xenopus laevis, rodents and humans as well as a new putative ortholog in T. rubripes.
The second family, previously known as Aurora-B [2,28] consists of cold-blooded vertebrate and mammalian Aurora-B as well as mammalian Aurora-C. Mammalian Aurora-B and Aurora-C are similarly related to the cold-blooded vertebrate Aurora presently known as "Aurora-B" in amphibians (X. laevis) and fish (D. rerio and T. rubripes). Searches of T. rubripes and D. rerio protein and DNA sequence databases detected several other putative serine/threonine kinase homologs but none were Auroras according to phylogenetic analyses. Thus, cold-blooded vertebrates appear to have only a single Aurora-A ortholog, a single Aurora-B-like homolog, and lack an Aurora-C ortholog. Conversely, Aurora-A, Aurora-B and Aurora-C appear to be ubiquitous to mammals (at least placentals) where they are encoded by separate chromosomal loci. It would appear that mammalian Aurora-B and Aurora-C evolved from a duplication event involving the ancestral Aurora-B found in cold-blooded vertebrates. This depiction of the evolutionary relationships of vertebrate Auroras was consistently determined by four different phylogenetic methods with high bootstrap or Bayesian posterior probability values (Fig. 2).
Comparisons of human Aurora-B and Aurora-C sequences to the resolved 3D structure of human Aurora-A [29] lends further support to the evolutionary scenario that vertebrate Aurora-B and Aurora-C are closely related paralogs (Fig. 3a). Of the 26 residues lining the ATP-binding active site, only three vary among the different human Aurora kinases; Leu215, Thr217 and R220 (numbering and residue identity based on Aurora-A), and all of these variants were specific to Aurora-A (Fig. 3b). Aurora-B and Aurora-C did not vary in their active site residues. Furthermore, all three Auroras have a carboxy-terminal destruction box (D-box) but only Aurora-A has the necessary amino-terminal A-box (also known as the D-box activating-domain) for its functional activation [30,31]. Collectively, these comparisons of structure and motifs support the phylogeny depicting an early divergence of Aurora-A from an Aurora-B / Aurora-C clade.
Figure 3. Comparisons of the catalytic domains of human Aurora-A, Aurora-B and Aurora-C kinases. A. Crystal structure of the catalytic domain of Human Aurora kinase with an adenosine molecule shown in the binding pocket (PDB ID 1muoA) [29]. Residues lining the active site are colored purple when invariant and red when variant. B, Multiple sequence alignment of Auroras. Using the same color scheme as the structure in panel A, residues identified to be lining the active site are identified with invariant residues among all three Auroras marked with an asterisk. Of the 26 residues lining the active site, only three vary among the different human Aurora kinases; Leu215, Thr217 and R220 (numbering and residue identity based on Aurora-A), and all of this variation was found in Aurora-A.
Non-chordate Evolution
The Aurora kinases of plants and invertebrates are all outgroup lineages to chordates / urochordates (Fig. 2). Although all phylogenetic methods strongly support the monophyly of chordate Aurora kinases, the exact ordering among nodes leading to the various plant and invertebrate clusters were not resolved with similarly high bootstrap or probability values. Placement of plant Aurora kinases between chordates and invertebrates might be an artifact of tree construction methods. (Plant, protist, fungal and invertebrate lineages were all highly diverged from vertebrate Aurora kinases as witnessed by their longer branch lengths.) The earliest lineages of the Aurora tree are those fungal model organisms with a single Aurora-like homolog S. cerevisiae (Ipl1) and S. pombe (Ark1). Other basal branches are the amitochondrial fungi, Encephalitozoon cuniculi, and the kinetoplast protist, Leishmania major [32].
Invertebrate Aurora kinases, including those of the model organisms C. elegans and D. melanogaster, occupy separate early branches and are not, as their current names suggest, orthologs to either Aurora-A or Aurora-B of vertebrates. An unrooted phylogenetic tree with only model organism species shows the same topology of vertebrate Auroras as the more species-rich tree rooted by PLK4 kinases (Fig. 4). However, similar kinases from C. elegans and D. melanogaster now cluster together. The unrooted tree suggests that the invertebrate Aurora-B kinase family evolved prior to the invertebrate Aurora-A kinase family although further examples from other species are desirable to confirm this hypothesis. The consensus scenario in both rooted and unrooted trees is that vertebrate Aurora kinases are paralogous, rather than orthologous, to their invertebrate counterparts.
Figure 4. Unrooted phylogenetic tree of Aurora kinases from human and model organisms. Tree was constructed using the maximum likelihood quartet puzzling method [43]. Scale bar represents 0.1 expected amino acid residue substitutions per site. Confidence estimates of nodes, fonts, and colours of species names correspond to Fig. 2.
Model Organisms in Context
Aurora-B and Aurora-C, as specific innovations in mammals, might have distinct protein-binding partners and cellular functions from those of Aurora-B kinases in amphibians. The perturbation of Aurora-B function in different systems suggests variable kinetochore-microtubule interactions [33]. Transfection of normal rat kidney cells with a kinase-inactive, dominant negative form of Aurora-B caused multiple defects in mitosis [34] while an Aurora-B kinase inactivating antibody seemed to have milder effects in Xenopus tissue culture cells [35]. Xenopus Aurora-A functions in the extrusion of the first polar body [36] while in C. elegans Aurora B plays a similar role [5]. Also, C. elegans Aurora-B binds to a protein CSC-1 which has no homolog in other studied systems [37]. While these studies used different experimental methods, the lack of direct orthology among vertebrate and invertebrate Aurora-A and Aurora-B might also account for functional differences in these systems.
The evolutionary analysis presented here also suggests revisiting the present Aurora nomenclature. Adams et al. [28] proposed a naming scheme where, irrespective of species, the original Aurora is known as Aurora-A (also called AIRK1, Aurora, Aurora-2, AIK, BTAK, human STK15, mouse STK6 and others), followed by Aurora-B (also known as AIRK-2, IAL, Aurora-1, AIK2, STK12 and others) and Aurora-C (or STK13). However, the proposed nomenclature fails to reflect evolutionary, and possibly functional, relationships among the Auroras. We suggest that Aurora-A be retained as the name for all orthologs in mammals and cold-blooded vertebrates. While Aurora-B and Aurora-C seem appropriate for mammalian versions, the ancestral cold-blooded vertebrate "Aurora-B" might be renamed "Aurora-BC". As for invertebrates, the so-called Aurora-A or Aurora-B genes are clearly not orthologs to their respective vertebrate counterparts. However, introducing a new nomenclature here might simply add further confusion to the field.
Evolution of an Anti-Cancer Target
There have been several recent reports of Aurora kinase inhibitors that are under development by pharmaceutical or biotechnology companies for cancer treatment. The compounds Hesperadin (Boehringer Ingelheim [21]) and ZM447439 (AstraZeneca [22]) are suggested to be targeted to Aurora-B. While both studies show lesser levels of compound inhibition of Aurora-A as well as several other kinases, neither report included Aurora-C in their kinase profile. Selective inactivation of multiple kinases is not an undesirable pharmaceutical profile for a small molecule inhibitor and, in fact, could be the best strategy to achieve maximal clinical efficacy of an anti-cancer agent [38]. Indeed, an intense area of anti-cancer research is the development of small molecular ATP analogues that generally target the kinase domain of protein kinases [39]. For example, Gleevec (also known as imatinib and made by Novartis) for chronic myelogenous leukemia, is a small-molecule inhibitor that targets BCR-ABL, c-Kit and platelet-derived growth factor receptor kinases [40]. Recently, a selective inhibitor of all three Aurora kinases, VX-680 (made by Vertex Pharmaceuticals), was reported to inhibit cell-cycle progression and induce apoptosis in various human tumor cell types and in vivo xenograft models [23]. Interestingly, although VX-680 is a potent inhibitor of all three Aurora kinases, its apparent inhibition constant is much lower for Aurora-A (0.6 nM) than for either Aurora-B (18 nM) or Aurora-C (4.6 nM). Again, the compound's greater affinity for Aurora-A, relative to Aurora-B and Aurora-C is compatible with the proposed evolutionary scenario of mammalian Auroras.
Evolutionary analysis shows that cell division Aurora kinases, while consistent in theme throughout eukaryotes, have undergone lineage-specific expansions and specialization in metazoans. Aurora-C is the least known of the Aurora kinases. Yet as an evolutionary innovation in mammals, further studies are very much warranted from the perspectives of better understanding its potential roles in both cell replication and tumor progression. A better functional understanding of Aurora-C would help clarify the evolutionary relationships of Aurora-B and Aurora-C in mammals relative to the ancestral Aurora-BC in cold-blooded vertebrates. Additionally, the close evolutionary and structural relationships between mammalian Aurora-B and Aurora-C offers the tantalizing opportunity to design dual kinase inhibitors that might circumvent potential tumor cell resistance to mono-target chemotherapeutics.
Database searches
All Aurora kinase orthologs and paralogs were initially collected from GenBank nonredundant protein database by performing separate searches using BLASTP [24] with human Aurora-A, Aurora-B and Aurora-C proteins as query sequences and a cut-off E-value of 1.0e-10. Since this dataset included additional kinases to the Auroras, preliminary multiple sequence alignments and phylogenetic analysis using program CLUSTALW v1.7 [41] served to identify the clade of all known Aurora kinases. Takifugu rubripes, Danio rerios and Ciona intestinalis homologs were obtained by BLASTP and TBLASTN [24] of species-specific protein and DNA sequence databases, respectively. The top five homologs from each species retrieved from separate searches with human Aurora-A, Aurora-B and Aurora-C were entered into a preliminary phylogenetic analysis using all retrieved Aurora kinases from Genbank. These analyses revealed that T. rubripes and D. rerios had orthologs to X. laevis Aurora-A and Aurora-B but not mammalian Aurora-C. C. intestinalis had a single Aurora-like kinase.
Phylogenetic and structure analysis
PLK4 kinases were selected as the outgroup for phylogenetic analyses because they were the most similar non-Aurora kinases to either human Aurora-A, Aurora-B or Aurora-C in multiple BLASTP [24] searches of the non-redundant protein database of GenBank. Using alternative kinases as outgroups made no difference to the topology of the Aurora clade. Initial multiple sequence alignments were performed using the program CLUSTALW v1.7 [41] with default settings and subsequently, refined manually using the program SEQLAB of the GCG Wisconsin Package v11.0 software package (Accelrys, San Diego, CA, USA). We removed regions with residues that could not be unambiguously aligned or that contained insertions or deletions. The final multiple sequence alignment was 240 amino acids in length. Pairwise comparisons for the proportion of similar residues were estimated from the length of the shortest sequence without gaps and the Blosum62 weighting matrix as implemented in the program OLDDISTANCES in GCG.
We constructed phylogenetic trees using distance neighbor-joining (NJ), maximum parsimony (MP), maximum likelihood quartet puzzling (QP), and Bayesian posterior probabilities (BP). NJ trees were based on pair wise distances between amino acid sequences using the programs NEIGHBOR and PROTDIST (Dayhoff option) of the PHYLIP 3.6 package [42]. The programs SEQBOOT and CONSENSE were used to estimate the confidence limits of branching points from 1000 bootstrap replications. ML tree topologies were constructed using the software PUZZLE 4.0 [43], employing 1000 puzzling steps, the JTT substitution matrix, estimation of rate heterogeneity using the gamma distribution model with eight rate categories, and the gamma-parameter estimation from the dataset. MP analysis was performed using PAUP4.0b5 software [44] where the number and lengths of minimal trees were estimated from 100 random sequence additions, while confidence limits of branch points were estimated by 1000 bootstrap replications. BP trees were constructed using the software MrBayes v3.0B4 [45,46]. Bayesian analysis used the mixed model of sequence evolution with random starting trees. Markov chains were run for 106 generations, burn-in values were set for 104 generations, and trees sampled every 100 generations. All trees were visualized using the program TREEVIEW v1.6.6 [47].
For the Aurora kinase phylogeny rooted with PLK4 kinases shown in Fig. 2, the log likelihood of the final ML tree was -8059.78. Four minimal length MP trees were recovered, 1522 steps in length with a consistency index (CI) of 0.5802 and a retention index (RI) of 0.6016. The variable branch arrangements were terminal nodes (human, pig and cow Aurora-B) which did not affect the central findings.
For the unrooted phylogeny of Aurora kinases of model organisms shown in Fig. 3, the log likelihood of the final ML tree was -4469.20. A single minimal length MP trees were recovered, 779 steps in length with a consistency index (CI) of 0.7214 and a retention index (RI) of 0.2786.
The SwissPDBviewer program [48] was used to obtain the surface representation of human Aurora-A kinase (PDB ID 1muoA). The active site residues, defined as being within 5A of the ADP cofactor, were identified using the program CAST [49]. The multiple sequence alignment for the three human Aurora kinase proteins was obtained using CLUSTALW [41]. Multiple sequence alignment and sequence GenBank accession numbers are available as Supplementary Information [see 1 and 2].
Authors' contributions
JRB conceived the study, performed the phylogenetic analysis and drafted the manuscript. KKK performed the 3D structural analyses and contributed to the draft manuscript. MLB participated in the preliminary phylogenetic analysis and contributed to the draft manuscript. PS and DRP both contributed to the draft of the manuscript and added key references.
This work was supported by Bioinformatics, Genetics Research, and the Microbial, Musculoskeletal and Proliferative Disease Center for Excellence in Drug Discovery, GlaxoSmithKline.
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Dehal P, Satou Y, Campbell RK, Chapman J, Degnan B, De Tomaso A, Davidson B, Di Gregorio A, Gelpke M, Goodstein DM, Harafuji N, Hastings KE, Ho I, Hotta K, Huang W, Kawashima T, Lemaire P, Martinez D, Meinertzhagen IA, Necula S, Nonaka M, Putnam N, Rash S, Saiga H, Satake M, Terry A, Yamada L, Wang HG, Awazu S, Azumi K, Boore J, Branno M, Chin-Bow S, DeSantis R, Doyle S, Francino P, Keys DN, Haga S, Hayashi H, Hino K, Imai KS, Inaba K, Kano S, Kobayashi K, Kobayashi M, Lee BI, Makabe KW, Manohar C, Matassi G, Medina M, Mochizuki Y, Mount S, Morishita T, Miura S, Nakayama A, Nishizaka S, Nomoto H, Ohta F, Oishi K, Rigoutsos I, Sano M, Sasaki A, Sasakura Y, Shoguchi E, T Shin-i, Spagnuolo A, Stainier D, Suzuki MM, Tassy O, Takatori N, Tokuoka M, Yagi K, Yoshizaki F, Wada S, Zhang C, Hyatt PD, Larimer F, Detter C, Doggett N, Glavina T, Hawkins T, Richardson P, Lucas S, Kohara Y, Levine M, Satoh N, Rokhsar DS: The draft genome of Ciona intestinalis: insights into chordate and vertebrate origins.
Science 2002, 298:2157-2167. PubMed Abstract | Publisher Full Text
Adams Richard R., Carmena Mar, Earnshaw William C.: Chromosomal passengers and the (aurora) ABCs of mitosis.
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Cheetham GM, Knegtel RM, Coll JT, Renwick SB, Swenson L, Weber P, Lippke JA, Austen DA: Crystal structure of aurora-2, an oncogenic serine/threonine kinase.
J Biol Chem 2002, 277:42419-42422. PubMed Abstract | Publisher Full Text
Castro A, Vigneron S, Bernis C, Labbe JC, Prigent C, Lorca T: The D-Box-activating domain (DAD) is a new proteolysis signal that stimulates the silent D-Box sequence of Aurora-A.
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Arlot-Bonnemains Y, Klotzbucher A, Giet R, Uzbekov R, Bihan R, Prigent C: Identification of a functional destruction box in the Xenopus laevis aurora-A kinase pEg2.
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Siman-Tov MM, Ivens AC, Jaffe CL: Identification and cloning of Lmairk, a member of the Aurora/Ipl1p protein kinase family, from the human protozoan parasite Leishmania.
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Shannon KB, Salmon ED: Chromosome dynamics: new light on Aurora B kinase function.
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Murata-Hori M, Wang YL: The kinase activity of aurora B is required for kinetochore-microtubule interactions during mitosis.
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Kallio MJ, McCleland ML, Stukenberg PT, Gorbsky GJ: Inhibition of aurora B kinase blocks chromosome segregation, overrides the spindle checkpoint, and perturbs microtubule dynamics in mitosis.
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text:
Visual Basic programming techniques are presented in a logical and easy-to-follow sequence that helps you really understand the principles involved in developing programs. The reader begins with learning the basics to write a first program and then moves on to adding voice, music, sound, and graphics. After reading this book, the reader will be able to write their own DLLs, create ActiveX controls, use object linking and embedding (OLE) and write Visual Basic programs that support multiple document interface, and much more. Various topics covered are: - Properties, Controls, and Objects - Graphics, Controls & Methods - Interfacing with Windows - Arrays, OLE, and other topics - Data Control and SQL - Multiple Document Interface - ActiveX- Sound Programming and DirectSound - Building ActiveX Controls and all the latest features of Visual Basic.
You can read this item using any of the following Kobo apps and devices:

subset: commoncrawl


text:
Family, Career and Community Leaders of America
|This article or section may have been copied and pasted from http://fcclainc.org/about-us/ (DupDet · CopyVios), possibly in violation of Wikipedia's copyright policy. Please remedy this by editing this article to remove any non-free copyrighted content and attributing free content correctly, or flagging the content for deletion. Please be sure that the source of the copyright violation is not itself a Wikipedia mirror. (September 2015)
Official FCCLA emblem
|Towards New Horizons
"Hacia Nuevos Horizontes"
|June 11, 1945Chicago, Illinois,
|Career and Technical Student organization, NGO
|Legal status
|Non-profit organization
|Family and Consumer Sciences education
|1910 Association Drive, Reston, Virginia
Region served
|United States
District of Columbia
Virgin Islands
Puerto Rico
|202,825 members in the United States[1]
Official language
|English[2] and Spanish[3]
Executive Director
|Sandy Spavone
National President
|Josh Sorbe (2015-2016)
National Chairperson
|Elliot Johnson (2015-2016)
|200,000 members and over 5,500 chapters
Formerly called
|Future Homemakers of America (1945-1977)
New Homemakers of America (1945-1965)
Family, Career and Community Leaders of America (FCCLA, Spanish: Líderes de las Familias, Carreras y Comunidades de América),[3] formerly known as Future Homemakers of America (FHA), is a nonprofit U.S. career and technical student organization (CTSO) for young men and women in family and consumer science education (FACS) in public and private schools through grade 12 across the United States. FCCLA is the only in-school student organization with the family as its central focus; is a vocational student organization that functions as an integral part of the Family and Consumer Sciences education curriculum and operates within the school system, and it provides opportunities for active student participation at local, state, and national levels.[2] FCCLA currently operates out of Reston, Virginia.
- 1 About FCCLA
- 2 History
- 3 National Programs
- 4 Competitive Events
- 5 Meetings and Conferences
- 6 References
- 7 External links
About FCCLA[edit]
FCCLA is a Non-profit organization that works with community service. It was formed in Chicago on June 11, 1945. As of the 2011 National Leadership Conference it had over 200,000 members in nearly 7,000 chapters across all 50 states as well as in the District of Columbia, the Virgin Islands, and Puerto Rico. The national headquarters is located at 1910 Association Drive, Reston VA 20191-1584.
We are the Family, Career and Community Leaders of America.
We face the future with warm courage and high hope.
For we have the clear consciousness of seeking old and precious values.
For we are the builders of homes,
Homes for America's future,
Homes where living will be the expression of everything that is good and fair,
Homes where truth and love and security and faith will be realities, not dreams.
We are the Family, Career and Community Leaders of America.
We face the future with warm courage and high hope.
- to provide opportunities for personal development and preparation for adult life
- to strengthen the function of the family as a basic unit of society
- to encourage democracy through cooperative action in the home and community
- to encourage individual and group involvement in helping achieve global cooperation and harmony
- to promote greater understanding between youth and adults
- to provide opportunities for making decisions and for assuming responsibilities.
- to prepare for the multiple roles of men and women in today's society
- to promote Family and Consumer Sciences and related occupations
FCCLA has a national membership of young men and women in nearly 6,500 chapters. There are 53 state associations including the District of Columbia, Puerto Rico, and the Virgin Islands. Since its founding in 1945, FCCLA has involved more than nine million youth. Former members are eligible to become members of Alumni & Associates.
Ten national officers (students) are elected by voting delegates at the annual National Leadership Conference and together make up the National Executive Council. The National Board of Directors is composed of adult representatives from education and business and four youth representatives. State associations and local chapters elect their own youth officers. State programs come under the direction of Family and Consumer Sciences education staff. Chapter advisers are Family and Consumer Sciences teachers.
Financial and Cooperative Support[edit]
FCCLA is supported primarily by student membership dues. Additional funds are raised from individuals, corporations, and foundations. FCCLA is endorsed by the U.S. Department of Education (Office of Vocational and Adult Education) and the American Association of Family and Consumer Sciences (AAFCS).
National Staff[edit]
An executive director leads the organization and heads a national staff that gives direction to and carries out programs, communications, membership services, and financial management.
FCCLA began on June 11, 1945, as Future Homemakers of America (FHA). It was created in Chicago, Illinois by Edna P. Amidon. During the years of segregation, sixteen southern states also operated the "New Homemakers of America." The two organizations merged in 1965. To reflect a focus on career preparation, the organization "HERO" (Home Economics Related Occupations) also merged with FHA to create FHA/HERO.
Name change[edit]
The name of the organization was changed to Family, Career and Community Leaders of America (FCCLA) in July 1999 at the National Leadership Meeting in Boston, Massachusetts by a majority of the voting delegates. A previous vote on a name change failed in 1995 at the organization's 50th Anniversary meeting in Washington, DC. A new name had been debated within the organization for many years[4] with several state associations choosing to break ranks and change their names to reflect the new mission of the organization.
National Programs[edit]
FCCLA has a variety of programs serving families, careers, and communities.
Competitive Events[edit]
Competitive Events is a program that contains all competition events existing in FCCLA.
- Competitive Events
- Family and Consumer Sciences Knowledge Bowl
- STAR Events
- FCCLA Contests
STAR Events[edit]
STAR Events (Students Taking Action with Recognition) is a very popular program incorporated into FCCLA. STAR Events are the competitive events that members can participate in to learn leadership, team work, communication and public speaking skills. STAR Events are no longer considered National Programs, now it is a "Competitive Events".
STAR Events offer individual skill development and application of learning through the following activities:
- Cooperative – teams work to accomplish specific goals
- Individualized – an individual member works alone to accomplish specific goals
- Competitive – individual or team performance measured by an established set of criteria.
- National-level STAR Events
- Advocacy
- Applied Technology
- Career Investigation
- Chapter Service Project (Display and Manual)
- Chapter Showcase (Display and Manual)
- Culinary Arts
- Digital Stories for Change
- Early Childhood
- Entrepreneurship
- Environmental Ambassador
- Fashion Construction
- Fashion Design
- Focus on Children
- Food Innovations
- Hospitality, Tourism and Recreation
- Illustrated Talk
- Interior Design
- Interpersonal Communications
- Job Interview
- Leadership
- Life Event Planning
- National Programs in Action
- Nutrition and Wellness
- Parliamentary Procedure
- Promote and Publicize FCCLA!
- Recycle and Redesign
- Teach and Train
- Virtual Poster
- Categories of Competition
- Junior (seventh grade through ninth grade members)
- Senior (tenth grade through twelfth grade members)
- Occupational (members who have completed an occupational family and consumer sciences course)
Meetings and Conferences[edit]
Chapter Meetings[edit]
Chapter Meetings include all the members of a certain chapter in the USA. There, they discuss current issues within the chapter. These usually take place within a school building.
Regional Meetings[edit]
Regional Meetings may also be called District Meetings. These are meetings where students within a geographical area may compete in STAR events and conduct business related to chapters in that area. District or regional STAR competition will result in groups or individual with a score above a set minimum (usually 50 or 70 out of 100 points) to the state STAR competition. In some states only a specific number of top achievers in each event are given the chance to advance.
State Conferences[edit]
State Conferences are held in a large city within a state and they are where students present their projects and STAR Events for the chance to go onto the National Leadership Conference. The only way to win the trip to the National Conference is to be the best in your category (such as Focus on Children, or Illustrated Talk) at State STAR Competition. These are usually held at the same city each year in your state.
National Leadership Conference[edit]
Each year a National Leadership Conference is held in a different city. The National Leadership Conference is where thousands of FCCLA Members gather to compete in STAR events to get a Gold, Silver, Bronze medal. Members also go to bring back new and important information towards their state. National Officers are also elected during this conference and introduced during the final night of the week-long conference.
The National Leadership Conference is held in a different US city each year. Some past and future National Leadership Conferences are:[5]
- 2002: Minneapolis, Minnesota
- 2003: Philadelphia, Pennsylvania
- 2004: Chicago, Illinois
- 2005: San Diego, California
- 2006: Nashville, Tennessee
- 2007: Anaheim, California
- 2008: Orlando, Florida
- 2009: Nashville, Tennessee
- 2010: Chicago, Illinois
- 2011: Anaheim, California
- 2012: Orlando, Florida
- 2013: Nashville, Tennessee
- 2014: San Antonio, Texas
- 2015: Washington, DC
- 2016: San Diego, California
- 2017: Nashville, Tennessee
- 2018: TBD (Central Region)
- 2019: Anaheim, California
- 2021: Nashville, Tennessee
- 2025: Nashville, Tennessee
National Cluster Meetings[edit]
National Cluster Meetings are similar to the National Leadership Conference, but without the STAR competitions. The conferences begin on a Friday night and last through Sunday night. Several motivational-type speakers are featured. There are three of these held every year in November, taking place in different regions of the USA. Anyone can attend these conferences.
- November 9–11: Atlanta, Georgia & Buffalo, New York
- November 16–18: Minneapolis, Minnesota & Denver, Colorado
- November 14–16: Jacksonville, Florida & Providence, Rhode Island
- November 21–23: Dallas, Texas & Cincinnati, Ohio
- November 13–15: Washington D.C.
- November 20–22: Louisville, Kentucky & Salt Lake City, Utah
- November 12–14: ABQ, NM & St. Louis, Missouri
- November 19–21: Pittsburgh, Pennsylvania
- November 11–13: Denver, Colorado
- November 11–13: Minneapolis, Minnesota
- November 18–20: Atlanta, Georgia
- November 9–11: Reno, Nevada
- November 16–18: Indianapolis, Indiana
- November 16–18: Oklahoma City, Oklahoma
- November 15–17: Spokane, Washington
- November 22–24:
- November 22–24: Omaha, Nebraska
- November 7-9: New Brunswick, New Jersey
- November 14-16: Little Rock, Arkansas
- November 21–23: Salt Lake City, Utah
- November 13–15: TBD (Pacific Region)
- November 13–15: TBD (North Atlantic Region)
- November 18–22: Dallas, Texas
- November 18–22: Indianapolis, Indiana
- ^ [Teen Times Magazine, Vol.69, No.1 ]
- ^ a b National FCCLA website - About us
- ^ a b FCCLA Puerto Rico website
- ^ Miller, Lisa M. (1993-12-16). "Where The Boys Are: Home Ec". New York Times (New York ed.). p. C1. Retrieved 2010-02-28.
- ^ FCCLA - Future Meetings
External links[edit]
- Official National FCCLA website
- Map and Links to all State FCCLA Pages provided by New York State FCCLA
- State of Iowa FCCLA Website with National Program Information and How-To Guides
- Official Florida FCCLA Website
- Official Minnesota FCCLA Website
- Official Minnesota FCCLA-HERO (occupational) Website
- Official Puerto Rico FCCLA Website
- Official Wisconsin FCCLA Website


text:
For medicines intended for chronic use, the number of patients studied before regulatory approval is insufficient to properly evaluate safety and long-term efficacy, requiring the need for new legislation, according to a study by European researchers published in this week's PLOS Medicine.
Current European guidelines specify that in order to fully evaluate the safety of medicines being developed for chronic (long-term) treatment of non-life threatening diseases, at least 1000 patients must take the new drug and that 300 and 100 patients must use the drug for 6 and 12 months, respectively, before approval by the European Medicines Agency.
In an analysis led by Ruben Duijnhoven from Utrecht University, the authors used information from the European Commission about 200 medicines approved between 2000 and 2010 to investigate whether the number of patients included were in compliance with the International Conference on Harmonisation E1 guidelines.
The authors found that the average number of patients studied before approval was 1708 for standard medicines and 438 for orphan medicines, medicines used to treat rare diseases. On average, medicines for chronic use (for example, asthma medications) were studied in more patients (2338) than those for intermediate use such as anti-cancer drugs (878) or short-term use such as antibiotics (1315). The safety and efficacy of chronic use was studied in fewer than 1000 patients for at least 6 and 12 months in 46.4% and 58.3% of new medicines, respectively. Finally, the authors found that among the 84 medicines intended for chronic use, 69 were studied in at least 300 patients for 6 months and 67 were studied in at least 100 patients for 12 months.
The authors say: "For medicines intended for chronic use, the number of patients studied before marketing is insufficient to evaluate safety and long-term efficacy. Both safety and efficacy require continued study after approval."<
|Contact: Sumrina Yousufzai
Public Library of Science


text: "He has always been a good little monkey and always very curious." With these words, H. A. and Margret Rey introduced the world to Curious George, securing him a place in the hearts of millions. For more than 65 years the inquisitive little monkey has appealed to generations both in books and now on the popular PBS KIDS show. In our Curious George store, you can shop for Curious George toys, party supplies, plush dolls, and other monkey-related merchandise.


text: On our way home from a trip, we just had to find a Zaxby's. We don't have any in Michigan. So our Navigator got us to this location. We were not disappointed! As expected, the chicken was exactly like we are used to it tasting. Too good to be true taste! It was a nice location in a town... read more


text:
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text:
Rockfax DescriptionThe centre of the orange wall is good and hard, especially at half-height. © ROCKFAX
UKC Logbook DescriptionRockfax 2005 name - Black Sabbath
Photo: Steve on Waka Plaka © SMc
Submit a new photo of this climb.
Retro flash. First time. Felt like onsight as not been on it for two years and couldn't remember moves. V hard crux. Harder than 7a. Great sequence. Well pleased.climberchristy - Lead rpt - 20/Feb/15 with Vanessa
Easier than Tarzan but more sustained. Soft 7a+Daniel Heath - Lead O/S - 01/Apr/13 with Alex
A bit mean for 7a and possibly a bit harder than cervezas y porrosSMc - Lead RP - 30/Mar/13 with Anne
Hidden - Lead dnf - 03/Dec/12
Fantastic route but stopper move. No way is it 7a. Really brick move. Dont think its a reach thing either just nails!!!julesp - Lead dog - 03/Dec/12 with fraser, stuart and kim
2nd go.Jonathan Emett - Lead RP - 22/Nov/12 with dennis
Hidden - Lead O/S - 09/Apr/12
Hidden - Lead β - 06/Jan/12
JonBrown - Lead dog - 05/Jan/11 with Hannah S, Gramps
dswansonlow - Lead O/S - 01/Jan/11 with Ed Searle
Robin Head - Lead dog - 01/Jan/11 with Joe Premier, Douggie Swanson-Low
Hidden - TR dnf - 01/Jan/11
Garh so close!Jo Davison - TR dnf - 01/Jan/11 with Dougie
davidliu - Lead O/S - 28/Dec/10 with Chris Rose, Umbreen Ahmed, Luke Walsh, Veronika Hvizdakova
Hidden - Lead β - 28/Dec/10
Hidden - 2nd β - 30/Apr/09
1 restBristoldave - Lead dog - 31/Dec/08 with mosel
Hidden - Lead β - 2008


text:
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American Building and RoofingRead MoreYou don't need a stopwatch to know that Jiffy Lube's services are fast, but if you had one, the Signature Service Oil Change would clock in at the 20-minute mark. And you'd be getting more than just an oil change. Jiffy Lube technicians also top off fluids, inflate tires, inspect key components, and diagnose issues before they happen—all in less time than it takes to replace a shattered windshield with Saran-Wrap. This blend of speed, quality, and preventative maintenance is at the core of Jiffy Lube's mission to maximize a vehicle's lifespan and keep it out of the repair shop. More than 20,000 of its technicians have completed an extensive training program certified by the National Institute for Automotive Service Excellence (ASE). These experts can perform many of the manufacturer-recommended services offered at dealerships, including air-filtration and electrical services—only without the need for appointments or long wait times. An impressive feat, considering that Jiffy Lube serves roughly 24 million customers each year.12807 Highway 99Everett, WA US
Darryl Moss Roof CareRead MoreKnowing that cleaning can damage a roof as much as help it, Darryl Moss Roof Care's technicians tailor their efforts to the needs of each surface, taking care not to put too much stress on the materials. Along with installing or repairing roofs and cleaning gutters, the crew takes to the ground to pressure wash decks, driveways, and sidewalks and oust the exterior moss that prevents homes from maintaining their natural tans.3413 98th Place SEEverett, WA US
E'CYCLE Roof CareRead MoreAt E'CYCLE Roof Care, each technician must undergo 80 hours of training before he or she can do so much as write an estimate. So you can be sure that each specialist who comes to your home will have the experience to address whatever your roof needs, whether it's gutter cleaning, minor repairs, a complete teardown, or Santa removal. They employ an array of eco-friendly tools and processes as they tend to each roof conundrum, ensuring that the services are safe for all plants, animals, and the environment.7342 West Lake Sammamish WayRedmond, WA US
Aldrich PaintingRead MoreWhile it can be hard choosing a paint color, finding a dependable painting company is easy! Just call the experts at Aldrich Painting in Seattle. When you need help on a painting project, make the right choice with Aldrich Painting. Don't let that little fixer-upper turn into a major issue in your home. Get it fixed with some help from the friendly handymen at Aldrich Painting.8645 22nd Avenue SouthwestSeattle, WA US


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Fairytales have been written about them and fetishes born of them. Here's where to find fabulous shoes that fit every style, size, and budget.Read More
André Wells loves a good shoe, right down to its sole.
With a treasure trove of glam footwear, Susanna Quinn designed a closet to match.
From jewel tones and metallics to booties and stacked heels, here are shoes to fall for this fall.
Want a dress pump you can walk in all day? You may know that a wider heel is more stable than a thin one, but here are other expert tips for choosing a shoe.
Nordstrom fashion director Gregg Andrews shares his shoe picks for the four looks every man wears at some point in life.
How to care for your shoes, how not to wear socks, and more.
Posted at 02:34 PM/ET, 08/14/2012 RSS | Permalink | Washingtonian.com Guides


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The provision of injectable cosmetic treatments, including dermal fillers and botulinum toxin, is to be controlled for the first time with the imminent launch of new rules in the form of a Government backed registration scheme.
This registration, certification and inspection scheme has been developed by the injectable cosmetics industry with the encouragement of Ministers to safeguard patients from treatments carried about by unqualified rogue practitioners. The Independent Healthcare Advisory Services (IHAS) will be running the industry-led shared regulation scheme.
There are currently an estimated 5,000 facilities carrying out an estimated 200,000 treatments a year in the UK. As treatments are elective, until now, providers of injectable cosmetic treatments have fallen outside the scope of watchdogs at the Care Quality Commission (CQC).
Says Dr Andrew Vallance-Owen, Chair of IHAS Shared Regulation Group, "This is excellent news for consumers and properly qualified practitioners. With growth of an estimated 25% of treatments carried out last year alone, the industry and the Department of Health recognised the need to safeguard patients by creating a system of registration and certification to reduce the risk of poor-practice within the sector."
Health Minister Mike O'Brien said:"Quality marking the organisations that provide injectable cosmetic treatments, such as Botox® and wrinkle fillers, will help protect the public from unscrupulous operators. It will clearly mark those who uphold the highest standards the industry can provide. This is why I have given my support and government funding to help set up the scheme. It will enable people who choose to have these treatments to be better informed of the risks and choices available to them."
Organisations and practitioners will be able to apply for registration through the website, with self assessment documents and supporting evidence submissions required. Applications for certification and registration will be reviewed by a team of experts, who will also run inspections by conducting site visits randomly selected, with only 24 hours' prior notice to providers. The scheme will be administered by CHKS on behalf of IHAS.
Industry leaders such as The Harley Medical Group which has 27 clinics, Transform which has 24 clinics and Sk:n. which has 34 clinics, have already indicated their commitment to registering their clinics once the scheme goes live in the next month.


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Chinese optics company Shenyang Zhongyi Optical and Electronic has announced that it is adding a super-fast standard lens to its range designed for the Micro Four Thirds system. The new 25mm lens features a maximum aperture of F0.95 but has a very small and lightweight body. Read more
Stories tagged with micro-four-thirds
Drone maker DJI has announced a pair of Micro Four Thirds aerial cameras including a model that can shoot lossless 4K Raw footage. The Zenmuse X5 and X5R are built around 16MP Four Thirds sensors, are compatible with a handful of small Micro Four Thirds lenses and can be flown on the company's Inspire 1 drones. Read more
Caldwell Photographic and Metabones have announced the Speed Booster Ultra for Micro Four Thirds: an updated design that uses more sophisticated glass and has been optimized for use with the relatively thick Micro Four Thirds filter stack. The latest Canon version also gains AF-S autofocus when used with Panasonic cameras: an improvement available via firmware update for existing users. Read more
Z Camera, a China-based photography startup, has introduced a connected Micro Four Thirds camera called the E1. Shaped like GoPro's HERO action cameras, the E1 carries a 16MP Four Thirds sensor and can record video at 4K 4096x2160 resolution. It provides Wi-Fi connectivity and an open platform for developers. Read more
Chinese lens adapter manufacturer Kipon has announced plans to introduce the first adapter that allows AF operation when a Canon EF or EF-S lens is attached to a Micro Four Thirds camera body. Previous adapters have either been entirely manual or, more lately, offered aperture control, but the Shanghai-based company has said that its next model will allow full frame and APS-C EOS system lenses to focus automatically too. Read more
Japanese optical manufacturer Kowa has released pricing for the three Micro Four Thirds lenses it first announced a year ago. The trio, Kowa Prominar MFT 12mm f/1.8, Prominar MFT 8.5mm f/2.8 and Prominar MFT 25mm f/1.8 are available now and will come in a choice of black, silver or green finishes. The lenses are all manual focus, and do not feature electrical contacts for communicating aperture or focus distance data to the camera. The company had them on show at the Broadcast Video Expo in London. Read more
We thought we'd try something a bit different for our video overview of the Olympus OM-D E-M5 II. Given that two of the major changes are improvements in its video features and stabilization, we thought we'd use the camera to shoot its own video and see how it behaves handheld. And, since the camera is environmentally sealed, we thought we'd venture beyond the office for a bit. See video
Three companies joined the Micro Four Thirds system standard group this morning, including DJI, maker of both consumer and professional-level drones. JDC (GuangZhou) Optical Co., a small Chinese optics manufacturer, and Flovel Co., a Japanese optical company, both also announced support. Read more
Flash manufacturer Cactus has updated firmware for its V6 wireless flash transceiver to include profiles for top end guns from Olympus and Panasonic's Micro Four Thirds and Four Thirds systems. Firmware 1.1.004 makes the V6 transmitter/receiver units compatible specifically with Olympus FL-50R, FL-36R and Panasonic FL-500R and FL-360R. Read more
Olympus is using Photokina to show a prototype 'Open Platform' camera module. Developed with the MIT Media Lab, the module is a Micro Four Thirds compatible unit that can be controlled from a smart device. Like Sony's QX series, the Olympus has its own shutter button but it also offers a hotshoe an is built around a more open software platform to allow developers to create apps to control it.
Panasonic has announced it is developing a 30mm f/2.8 Macro lens for the Micro Four Thirds system. The lens will be compatible with the latest generation 240 frame-per-second autofocus and will include image stabilization. No further details of specification, price or time-scale have yet been provided.
Lens adapter manufacturer Metabones has launched a pair of long-awaited Canon EF to Micro Four Thirds lens adapters. The first adapter is the Smart Mount version which allows electronic control of the aperture in a Canon lens from a Micro Four Thirds camera, as well as correct recording of EXIF information and activation of Image Stabilization where present. Also debuting is an EF to Micro Four Thirds Speed Booster. Read more
Kodak is arguably the most famous name of all in photography, but it ultimately failed to manage the transition from film to digital, and ended up exiting the consumer imaging business altogether in 2013. But now JK Imaging, which licenses the Kodak name, has created an interchangeable lens camera. The Pixpro S-1 is an entry-level model that's designed to attract budding photographers who are buying their first system camera. Click through to read our first impressions.
Update: Consumer electronics maker JVC Kenwood has joined the Micro Four Thirds standard and said it will develop products for the system. The company is showing two prototype 4K-capable cameras, including a compact, handheld model at NAB in Las Vegas. We stopped by the JVC Kenwood booth and got a first glimpse of the cameras on display. Interestingly, the company says both cameras will have Super 35 sensors (around 21 x 12mm), which is wider than the original Four Thirds sensor format which the standard was designed around. Learn more
Kodak famously failed to adapt to the transition from film to digital photography, and finally stopped making digital cameras in early 2012. Now the famous old brand has been resurrected by JK Imaging Ltd, which is producing cameras in partnership with Asia Optical. We got a quick look at some of the 2014 product portfolio earlier this year at CES but this week we had a more detailed briefing at a European press event. Click through to take a closer look.
Japanese optical company Kowa - best known for its spotting scopes and binoculars - has revealed that it plans to make three lenses for Micro Four Thirds cameras. The Kowa Prominar 8.5mm F2.8 MFT, 12mm F1.8 MFT and 25mm F1.8 MFT will all feature manual focus and aperture control, and use low-dispersion XD glass and aspheric elements to minimise distortion and aberrations. They're due to be released in summer 2014.
Panasonic has announced its latest flagship Micro Four Thirds camera, the Lumix DMC-GH4. It's designed as a 'hybrid camera' that can shoot both stills and videos, and the emphasis of the improvements is clearly on the latter. Its revised 16MP Live MOS sensor and Venus Engine IX processor allow for 4K video, 12 fps continuous shooting and 1080p shooting at bitrates as high as 200Mbps. An optional 'interface unit' adds five SDI and two XLR terminals, and permits 10-bit 4:2:2 output with time code.
CES 2014: Panasonic has formally announced the Leica DG Nocticron 42.5mm F1.2 ASPH OIS fast portrait prime for Micro Four Thirds. The lens, first revealed in prototype form back at the Photokina trade show in September 2012, offers an 85mm equivalent field of view, optical image stabilisation, and the brightest aperture of any autofocus lens on the system. It's The lens will be available during the first quarter of 2014 at suggested prices of $1,599/€1,499/£1,299.
Hong Kong-based lens maker SLR Magic has announced an addition to its family of video-oriented manual focus fast primes for Micro Four Thirds. The 17mm T1.6 offers an angle of view equivalent to 34mm on full frame, and has geared focus and aperture rings. It will be available at the end of December 2013.
Forget the Zeiss Otus 55mm F1.4, Sony Alpha 7R and RX10, Nikon 58mm F1.4 or the tiny Panasonic GM1 - last week's real news was Lomography's introduction of an 'Experimental Lens Kit' for Micro Four Thirds. Comprising a 24mm F8 standard lens, a 12mm F8 wideangle and a 160° F8 fisheye, the kit costs £79 / €89. Each of the lenses even has a built-in shutter with speeds of 1/100sec and Bulb, allowing in-camera multiple exposures, plus a T mode to hold the shutter open for normal live view. In addition all three have a slot for colour gel filters. Click through for full details.
We've been shooting with the Olympus PEN E-P5 for some months now and have just completed our review. The arrival of the E-M1 may have grabbed the limelight in recent weeks but the latest PEN deserves its share of the attention. Although it continues the classic PEN look, it shares most of its specifications with the E-M5, which should make it pretty special - but what's it like to use? Read our review to find out.
We've had more time to shoot with the Olympus E-M1 and have extended our coverage of its AF performance. In addition to incorporating real-world Continuous Autofocus examples and commentary, we've also spent more time shooting with it alongside an E-5, to see exactly how the two compare, and amended our impressions accordingly.
The O-MD E-M1 has just been announced and takes its place as both Olympus' flagship Micro Four Thirds camera and the successor to the E-5 DSLR. We've been spending some time with a production unit, taking the new 16.3 megapixel Live MOS sensor for a spin in a variety of conditions. Follow the link to learn more about this high-end mirrorless interchangeable lens camera.
Olympus has announced the OM-D E-M1, now the flagship of its Micro Four Thirds lineup. Rather than calling it the follow-up to the E-M5, Olympus says that the E-M1 is actually the 'successor' to the E-5, the Four Thirds camera introduced back in 2010. The E-M1's standout feature is its new 16.3MP Live MOS sensor with on-chip phase-detection autofocus, designed to work with legacy Four Thirds lenses.
Olympus has unveiled a high-end standard zoom to match the E-M1: the M.Zuiko Digital ED 12-40mm F2.8 PRO. It offers a 24-80mm equivalent range and is dust, splash and, freezeproof, and uses a manual focus clutch design similar to the 12mm F2 and 17mm F2.8 primes. Olympus has also announced the development of a matching 40-150mm F2.8 telezoom, which is scheduled for release next year. Click through for more details.
It's an open secret that many compact cameras are produced by OEMs - companies that produce large numbers of products that are then sold under other brand names. There are also consumer-grade zooms from big name manufacturers that look much alike (we know for a fact that third-party makers commonly create lenses for the bigger brands). But we were still surprised to read about Sigma's latest patent for a 75mm F1.8 prime lens...
Panasonic has announced the Lumix DMC-GX7 - the follow-up to the DMC-GX1 - which is its first mirrorless interchangeable lens camera to include in-body image stabilization. This 16MP, rangefinder-style camera also includes a high-resolution, widescreen EVF that can be tilted upwards 90 degrees. Panasonic claims that their newly designed Live MOS sensor improves both detail and color saturation by 10%. Other features of note include a tilting LCD, a 'silent shooting' mode, focus peaking, 1080/60p videos, and Wi-Fi with NFC capability.
Alongside the enthusiast-oriented DMC-GX7, Panasonic has announced the Leica DG Nocticron 42.5mm F1.2 - the fastest autofocus lens ever created for the Micro Four Thirds system. If you're getting a sense of deja vu that's because Panasonic actually announced this lens already (sort of) at last year's Photokina tradeshow in Cologne, Germany. But what was then a dummy lens behind glass now appears to be a real product, albeit one without any firm availability date or pricing information.
Panasonic introduces the Lumix GX7, an enthusiast-targeted Micro Four Thirds mirrorless camera with a 16MP sensor and both a tilting LCD and a tilting EVF. We get hands-on with this new M43 model.
Just posted: Our review of the Olympus Body Cap Lens 15mm F8. In essence this is a tiny three element optic hidden inside a body cap, and probably the cheapest lens of any description made by any camera manufacturer. But is it any good? In the latest of our lens reviews in collaboration with DxOMark, we take a look both at how well it performs in studio testing, and in real-world use. Does it have any place in the Micro Four Thirds user's camera bag? Click through to find out.
Metabones has introduced Nikon G-type versions of its Speed Booster lens adapter for Micro Four Thirds and Sony NEX cameras, which include a control ring for aperture setting with lenses that don't have aperture rings of their own. The Speed Booster itself is a lens adapter that that reduces the focal length by a factor of 0.71x, and increases the maximum aperture by 1 stop, effectively allowing lenses to give very similar angle of view and depth of field control on APS-C mirrorless cameras as they do on full frame. The Nikon G-type adapters are available to buy now for $429 from Metabones' website.
Just Posted: Our detailed, hands-on Olympus PEN E-P5 preview. We've been using a pre-production E-P5 for the last few days and have had a dig beyond the specifications to discover how the latest range-topping PEN behaves. We investigate the camera's latest features, including its easy-connect Wi-Fi, its degree of customization and its '2x2' dial behavior. We also take a look at how it compares to the E-P3 and OM-D E-M5, and how the high resolution VF-4 handles on the E-P5 and existing models.
Olympus has announced the PEN E-P5, the fourth in its range of enthusiast-targeted, rangefinder-style Micro Four Thirds cameras. The E-P5 takes the 16MP sensor that has appeared in the company's other models and adds a five-axis image stabilization system and shutter capable of shooting at 1/8000th of a second amongst a host of tweaks and feature improvements. The camera will available from May at around $1,000/£900/€1000 body only. The company has also announced black versions of its 17mm, 45mm and 75mm F1.8 prime lenses, priced the same as their silver counterparts. There is also a 2.4M dot LCD electronic viewfinder, the VF-4.
Sigma USA has given the price and introduction date of the 60mm F2.8 DN Art lens for mirrorless systems, originally announced at CP+. The 60mm DN will be available in the US for both Micro Four Thirds and Sony E-mount from mid-May at a cost of around $239. It will offer a 90mm equivalent field-of-view when mounted on Sony NEX bodies or 120mm equivalent on Micro Four Thirds cameras. This third lens for mirrorless cameras from Sigma (joining the affordable 19mm F2.8 DN Art and 30mm F2.8 DN Art), will also be available in a choice of black or silver finishes.
We've just posted our Panasonic Lumix DMC-G6 preview, covering Panasonic's newest Micro Four Thirds mirrorless interchangeable lens camera. The G6 comes barely a year after the G5, and offers several updates, including a 1.44 million-dot OLED electronic viewfinder and the same sensor as the GH2. Its body has also been restyled and the touch-sensitive technology of its fully-articulated screen has been upgraded. Like its little brother the GF6, the G6 also includes built-in Wi-Fi connectivity with Near Field Communication (NFC). Click through for our hands-on preview.
Panasonic has announced the Lumix DMC-G6 - the latest in its mass market series of DSLR-styled mirrorless cameras. The G6 gains considerably improved movie capabilities, including full exposure control, an external mic socket and the sensor from the GH2. It also adds the NFC-aided Wi-Fi for simple remote control and image download that we first saw in the GF6.
Panasonic has created the Lumix G Vario 14-140mm F3.5-5.6 ASPH Power OIS, a second-generation 10x zoom for Micro Four Thirds cameras. The lens offers a smaller, lighter, less-expensive alternative to the original G Vario HD 14-140mm F4.0-5.8 ASPH Mega OIS. The latest version features three aspheric and two ED elements and an internal focus design with linear stepper motors to make the most of the faster focus processing of the latest Micro Four Thirds bodies.
Just Posted: Our Panasonic Lumix DMC-GH3 review. The GH3 is the latest model in Panasonic's range-topping series of Micro Four Thirds cameras that aims to offer a tool as suited to keen film makers as enthusiast photographers. The GH3 has added a host of video industry-requested features as well as promising the best-yet stills image quality from a GH camera. However, the last year or so has seen other camera makers take an interest in movie shooting, so has Panasonic done enough to stay ahead? Read our review to find out.
Just Posted: Our hands-on Panasonic Lumix DMC-GF6 preview. The GF6 expands the capabilities of Panasonic's GF series away from the point-and-shoot focus that it had increasingly pursued. The latest model adds a more sophisticated touch-screen and additional control points that will benefit a range of users but it's the NFC-mediated Wi-Fi system that we found really interesting. Add this on top of the 16MP sensor from the GX1 and you have a compelling combination of features. Click through to find out more.
Panasonic has announced the Lumix DMC-GF6 - a 16MP entry-level mirrorless camera with Wi-Fi. Like many of its competitors it has a capacitive touchscreen, that can tilt both downwards and upwards to face forwards for self-portraits. It gains a compact-camera style zoom lever around the shutter release that can alternatively be used to set exposure compensation, and an exposure mode dial on the top plate. It's also the first interchangeable lens camera with Near Field Communication (NFC) that allows setup of Wi-Fi connections with compatible smartphones and tablets, simply by tapping the devices together. Movie recording is available at 1080p30 in either MP4 or AVCHD format.
Blackmagic Design has announced a pocket-sized 1080p movie camera capable of 422 ProRes capture with promises of lossless CinemaDNG to be added via firmware. The Blackmagic Pocket Cinema Camera uses a Super 16 imaging area (around 12.5 x 7.4mm - slightly smaller than a 1" sensor), and an 'active' Micro Four Thirds lens mount, giving full aperture control of native lenses. The camera can capture footage in Apple's 10-bit 4:2:2 ProRes format Blackmagic promising to add the open, lossless CinemaDNG Raw standard later. The company has said this will cost just $995 and be available from July.
SLR Magic has announced its Monster Lens II spotting scope for Micro Four Thirds cameras. The optic mounts directly on the camera body, allowing users to shoot distant images, commonly referred to as 'digiscoping'. The 12-36x50 ED lens gives an equivalent optical zoom range of 840-2,520mm and aims to keep image quality high with extra-low dispersion optics and multi-coated glass elements. It will be available from June 2013 at a suggested retail price of $799. Click through to to read more.
Sigma US has announced the price and availability for its three latest 'Art' series prime lenses - the 19mm f/2.8 DN and 30mm f/2.8 DN for mirrorless cameras, and the 30mm f/1.4 for APS-C DSLRs. The DN lenses will be available for street price of $199 and the redesigned 30mm f/1.4 will be available in Canon, Nikon and Sigma mounts for $499. All three will start shipping from the end of this month. No details were given about the 60mm f/2.8 lens also announced during the CP+ tradeshow.
CP+ 2013: Panasonic has added a 42.5mm F1.2 portrait lens and 150mm F2.8 super-telephoto prime to its lens roadmap for Micro Four Thirds, for release in the near future. The lenses, shown in prototype form at Photokina 2012, last September, are shown as being ready for release just after the 14-42mm II ASPH. kit zoom launched this week.
CP+ 2013: Tamron is showing off its newly-announced 14-150mm F3.5-5.8 Di III VC stabilized superzoom lens for Micro Four Thirds, while Olympus has a revised version of its 75-300mm F4.8-6.7. Though Tamron hasn't yet announced the price or availability of the 14-150mm, the prototype it has on display is working and the company gave us a hint about how much it will charge.
Tamron has announced that it's developing an image stabilised superzoom lens for Micro Four Thirds cameras. The 14-150mm F/3.5-5.8 Di III VC (Model C001) is poised to become the first third-party zoom for the system, and will offer a 28-300mm equivalent focal length range. It uses the company's Vibration Control (VC) system to counteract hand-shake, and a stepper motor for fast and silent autofocus. The lens will also feature a metal barrel and be available in a black or silver finish. Price and availibility are still to be confirmed.
CP+ 2013: Sigma has announced four additions to its 'Art' range of prime lenses, including a 60mm F2.8 DN lens for mirrorless cameras and an updated 30mm F1.4 DC for APS-C DSLRs. Alongside these are redesigned versions of its 30mm and 19mm F2.8 DN lenses for mirrorless in metal bodies. Like these lenses, the 60mm F2.8 DN features a metal casing and will be available for the Sony E and Micro Four Thirds mounts. It will offer a 90mm equivalent field of view on Sony NEX cameras or 120mm equivalent coverage of Micro Four Thirds bodies. The Sigma 30mm F1.4 DC is a completely redesigned version of the popular normal lens for APS-C DSLRs - it will be available in Canon, Nikon and Sigma mounts. Price and availability details have not been given.
CP+ 2013: Panasonic has announced the Lumix G Vario 14-42mm F3.5-5.6 II Asph. Mega O.I.S - its latest affordable kit lens for Micro Four Thirds mirrorless cameras. The 14-42mm F3.5-5.6 II is the company's fourth variable aperture standard zoom (following the 14-45mm, original 14-42mm and 14-42mm power zoom), and gains two aspherical elements to help make the lens smaller than the existing version. The 14-42mm II will be available as a kit option with both the DMC-GF5 and DMC-G5 in most markets.
Olympus has issued a press release confirming JK Imaging and four other companies have formally signed-up to the Micro Four Thirds standard. JK Imaging announced last week that it would be offering MFT cameras under the Kodak brand. Australian company Blackmagic Design, which already offers a movie camera with a passive Micro Four Thirds mount and is rumored to be working on a fully compliant version, also joins. The other three signatories are less consumer-facing.
Just a week after announcing it was licensing the Kodak brand name, JK Imaging has been showing a Micro Four Thirds camera at a press conference in China. Details are vague but the camera, reported to be called the S1, does appear to be sporting the official Micro Four Thirds logo. The camera, which will offer Wi-Fi for communication with smartphones, is said to be based around a Sony CMOS sensor. (via PetaPixel)


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SEND TO A FRIEND : Buzzing Brains Remote Control Car
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Bought this for my 2 year old grandson, he soon got the hang of it and loves it.
First remote control car
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29 Dec 2013


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linn energy llc-units (LINE:NASDAQ GS)
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Rockfax Description28m. Climb the cracked rib rightwards then the open groove to the final steepening. Swim up this to a tough exit. © ROCKFAX
took the left-hand at the end the crack looked too polishedsteve2006 - Lead - Jun/10
Hidden - Lead O/S - 15/May/09
Hidden - 2nd - 15/May/09


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Our daily countdown of the top newsmakers, groundbreakers and world-class fakers.
Says she recorded a hole in one during her first round of golf, matching Tiger's success during their first date. (previous ranking: unranked)
EA Sports apparently wants to partner with someone who occasionally wins majors. (4)
10. (tie) Los Angeles' drinking water
It's the human remains that give it that special bouquet. (unranked)
Bulls star back after 18 months of rehab and lame-ass Adidas commercials. (unranked)
Born this way ... except for the hideous tats and plastic surgery. (10)
Showing their horns, only because they couldn't unload their season tickets. (1)
His family's cartoon show would be just like Kardashians', only with a little less VD. (unranked)
Looks like his plan to keep Washington Redskins name is being ... uh ... tomahawked. (unranked)
It ain't exactly the breakup of the Beatles, now is it? (unranked)
Grounded temporarily Tuesday, permanently tonight or tomorrow. (unranked)
President's team would surrender nuclear codes before they'd give up miniscule enrollment numbers. (unranked)
Seattle effect: Aborted trade to Seahawks has Viking raining tears. (unranked)
Sidney Rice, Marshall Henderson, Jesse Jackson Jr., Miguel Cabrera's groin, Everett Golson, Marilyn Tavenner, Kevin Durant, angry marlins, Bob Barker, Jared Sullinger, Google's mystery islands, Dick Durbin, Kolten Wong, Brandon Meriweather, Chris Brown, St. Jude storm, Conrad Murray, Obamacare Girl, Jason Tarver, Mike Pouncey, Dexter Manley, Beanie Wells, Vodka Samm, Penn State, Julianne Hough, Bravehearts, NSA .
Kevin Cusick talks fantasy football, and whatever else comes up, with Bob Sansevere and "The Superstar" Mike Morris on Thursdays on Sports Radio 105 The Ticket. Follow him at twitter.com/theloopnow.