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The city of Xi'an – famed for being home to the Terracotta Army – plays host each September to a carnival of folklore events. It aims, through...
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China Public Holidays
Below are listed Public Holidays for the January 2014-December 2015 period.
In addition to the Public Holidays listed, other holidays may be observed locally and certain groups have official Public Holidays on the following dates:
8 Mar International Women's Day.
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Seven days' public holidays from Lunar New Year's Eve
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A DNA topoisomerase IB in Thaumarchaeota testifies for the presence of this enzyme in the last common ancestor of Archaea and Eucarya
Brochier-Armanet, Céline
Gribaldo, Simonetta
Forterre, Patrick
Biology Direct
DNA topoisomerase IB (TopoIB) was thought for a long time to be a eukaryotic specific enzyme. A shorter version was then found in viruses and later on in several bacteria, but not in archaea. Here, we show that a eukaryotic-like TopoIB is present in the recently sequenced genomes of two archaea of the newly proposed phylum Thaumarchaeota. Phylogenetic analyses suggest that a TopoIB was present in the last common ancestor of Archaea and Eucarya. This finding indicates that the last common ancestor of Archaea and Eucarya may have harboured a DNA genome.
This article was reviewed by Eugene Koonin and Anthony Poole
Related Articles
Evidence from glycine transfer RNA of a frozen accident at the dawn of the genetic code
Bernhardt, Harold S
Tate, Warren P
Biology Direct
Transfer RNA (tRNA) is the means by which the cell translates DNA sequence into protein according to the rules of the genetic code. A credible proposition is that tRNA was formed from the duplication of an RNA hairpin half the length of the contemporary tRNA molecule, with the point at which the hairpins were joined marked by the canonical intron insertion position found today within tRNA genes. If these hairpins possessed a 3'-CCA terminus with different combinations of stem nucleotides (the ancestral operational RNA code), specific aminoacylation and perhaps participation in some form of noncoded protein synthesis might have occurred. However, the identity of the first tRNA and the initial steps in the origin of the genetic code remain elusive.
Here we show evidence that glycine tRNA was the first tRNA, as revealed by a vestigial imprint in the anticodon loop sequences of contemporary descendents. This provides a plausible mechanism for the missing first step in the origin of the genetic code. In 448 of 466 glycine tRNA gene sequences from bacteria, archaea and eukaryote cytoplasm analyzed, CCA occurs immediately upstream of the canonical intron insertion position, suggesting the first anticodon (NCC for glycine) has been captured from the 3'-terminal CCA of one of the interacting hairpins as a result of an ancestral ligation.
That this imprint (including the second and third nucleotides of the glycine tRNA anticodon) has been retained through billions of years of evolution suggests Crick's 'frozen accident' hypothesis has validity for at least this very first step at the dawn of the genetic code.
This article was reviewed by Dr Eugene V. Koonin, Dr Rob Knight and Dr David H Ardell.
Related Articles
Pitfalls of the most commonly used models of context dependent substitution
Lindsay, Helen
Yap, Von Bing
Ying, Hua
Huttley, Gavin A
Biology Direct
Neighboring nucleotides exert a striking influence on mutation, with the hypermutability of CpG dinucleotides in many genomes being an exemplar. Among the approaches employed to measure the relative importance of sequence neighbors on molecular evolution have been continuous-time Markov process models for substitutions that treat sequences as a series of independent tuples. The most widely used examples are the codon substitution models. We evaluated the suitability of derivatives of the nucleotide frequency weighted (hereafter NF) and tuple frequency weighted (hereafter TF) models for measuring sequence context dependent substitution. Critical properties we address are their relationships to an independent nucleotide process and the robustness of parameter estimation to changes in sequence composition. We then consider the impact on inference concerning dinucleotide substitution processes from application of these two forms to intron sequence alignments from primates.
We prove that the NF form always nests the independent nucleotide process and that this is not true for the TF form. As a consequence, using TF to study context effects can be misleading, which is shown by both theoretical calculations and simulations. We describe a simple example where a context parameter estimated under TF is confounded with composition terms unless all sequence states are equi-frequent. We illustrate this for the dinucleotide case by simulation under a nucleotide model, showing that the TF form identifies a CpG effect when none exists. Our analysis of primate introns revealed that the effect of nucleotide neighbors is over-estimated under TF compared with NF. Parameter estimates for a number of contexts are also strikingly discordant between the two model forms.
Our results establish that the NF form should be used for analysis of independent-tuple context dependent processes. Although neighboring effects in general are still important, prominent influences such as the elevated CpG transversion rate previously identified using the TF form are an artifact. Our results further suggest as few as 5 parameters may account for ~85% of neighboring nucleotide influence.
This article was reviewed by Dr Rob Knight, Dr Josh Cherry (nominated by Dr David Lipman) and Dr Stephen Altschul (nominated by Dr David Lipman).
Related Articles
The evolution of domain-content in bacterial genomes
Molina, Nacho
van Nimwegen, Erik
Biology Direct
Across all sequenced bacterial genomes, the number of domains nc in different functional categories c scales as a power-law in the total number of domains n, i.e. nc∝nαc, with exponents αc that vary across functional categories. Here we investigate the implications of these scaling laws for the evolution of domain-content in bacterial genomes and derive the simplest evolutionary model consistent with these scaling laws.
We show that, using only an assumption of time invariance, the scaling laws uniquely determine the relative rates of domain additions and deletions across all functional categories and evolutionary lineages. In particular, the model predicts that the rate of additions and deletions of domains of category c is proportional to the number of domains nc currently in the genome and we discuss the implications of this observation for the role of horizontal transfer in genome evolution. Second, in addition to being proportional to nc, the rate of additions and deletions of domains of category c is proportional to a category-dependent constant ρc, which is the same for all evolutionary lineages. This 'evolutionary potential' ρc represents the relative probability for additions/deletions of domains of category c to be fixed in the population by selection and is predicted to equal the scaling exponent αc. By comparing the domain content of 93 pairs of closely-related genomes from all over the phylogenetic tree of bacteria, we demonstrate that the model's predictions are supported by available genome-sequence data.
Our results establish a direct quantitative connection between the scaling of domain numbers with genome size, and the rate of addition and deletions of domains during short evolutionary time intervals.
This article was reviewed by Eugene V. Koonin, Martijn A. Huynen, and Sergei Maslov.
Related Articles
Are we degenerate tetraploids? More genomes, new facts
Abbasi, Amir Ali
Biology Direct
Within the bilaterians, the appearance and evolution of vertebrates is accompanied by enormous changes in anatomical, morphological and developmental features. This evolution of increased complexity has been associated with two genome duplications (2R hypothesis) at the origin of vertebrates. However, in spite of extensive debate the validity of the 2R hypothesis remains controversial. The paucity of sequence data in early years of genomic era was an intrinsic obstacle in tracking the genome evolutionary history of chordates.
In this article I review the 2R hypothesis by taking into account the recent availability of genomic sequence data for an expanding range of animals. I argue here that genetic architecture of lower metazoans and representatives of major vertebrate and invertebrate lineages provides no support for the hypothesis relating the origin of vertebrates with widespread gene or genome duplications.
It appears that much of the genomic complexity of modern vertebrates is very ancient likely predating the origin of chordates or even the Bilaterian-Nonbilaterian divergence. The origin and evolution of vertebrates is partly accompanied by an increase in gene number. However, neither can we take this subtle increase in gene number as an only causative factor for evolution of phenotypic complexity in modern vertebrates nor we can take it as a reflection of polyplodization events early in their history.
This article was reviewed by Eugene Koonin, Joshua Cherry (nominated by David Lipman), and Jerzy Jurka.
Related Articles
Activating and inhibiting connections in biological network dynamics
McDonald, Daniel
Waterbury, Laura
Knight, Rob
Betterton, M D
Biology Direct
Many studies of biochemical networks have analyzed network topology. Such work has suggested that specific types of network wiring may increase network robustness and therefore confer a selective advantage. However, knowledge of network topology does not allow one to predict network dynamical behavior – for example, whether deleting a protein from a signaling network would maintain the network's dynamical behavior, or induce oscillations or chaos.
Here we report that the balance between activating and inhibiting connections is important in determining whether network dynamics reach steady state or oscillate. We use a simple dynamical model of a network of interacting genes or proteins. Using the model, we study random networks, networks selected for robust dynamics, and examples of biological network topologies. The fraction of activating connections influences whether the network dynamics reach steady state or oscillate.
The activating fraction may predispose a network to oscillate or reach steady state, and neutral evolution or selection of this parameter may affect the behavior of biological networks. This principle may unify the dynamics of a wide range of cellular networks.
Reviewed by Sergei Maslov, Eugene Koonin, and Yu (Brandon) Xia (nominated by Mark Gerstein). For the full reviews, please go to the Reviewers' comments section.
Related Articles
Functional insight into Maelstrom in the germline piRNA pathway: a unique domain homologous to the DnaQ-H 3'–5' exonuclease, its lineage-specific expansion/loss and evolutionarily active site switch
Zhang, Dapeng
Xiong, Huiling
Shan, Jufang
Xia, Xuhua
Trudeau, Vance L
Biology Direct
Maelstrom (MAEL) plays a crucial role in a recently-discovered piRNA pathway; however its specific function remains unknown. Here a novel MAEL-specific domain characterized by a set of conserved residues (Glu-His-His-Cys-His-Cys, EHHCHC) was identified in a broad range of species including vertebrates, sea squirts, insects, nematodes, and protists. It exhibits ancient lineage-specific expansions in several species, however, appears to be lost in all examined teleost fish species. Functional involvement of MAEL domains in DNA- and RNA-related processes was further revealed by its association with HMG, SR-25-like and HDAC_interact domains. A distant similarity to the DnaQ-H 3'–5' exonuclease family with the RNase H fold was discovered based on the evidence that all MAEL domains adopt the canonical RNase H fold; and several protist MAEL domains contain the conserved 3'–5' exonuclease active site residues (Asp-Glu-Asp-His-Asp, DEDHD). This evolutionary link together with structural examinations leads to a hypothesis that MAEL domains may have a potential nuclease activity or RNA-binding ability that may be implicated in piRNA biogenesis. The observed transition of two sets of characteristic residues between the ancestral DnaQ-H and the descendent MAEL domains may suggest a new mode for protein function evolution called "active site switch", in which the protist MAEL homologues are the likely evolutionary intermediates due to harboring the specific characteristics of both 3'–5' exonuclease and MAEL domains.
This article was reviewed by L Aravind, Wing-Cheong Wong and Frank Eisenhaber. For the full reviews, please go to the Reviewers' Comments section.
Related Articles
On the brink between extinction and persistence
Pertoldi, Cino
Bach, Lars A
Loeschcke, Volker
Biology Direct
The nature of size fluctuations is crucial in forecasting future population persistence, independently of whether the variability stems from external forces or from the dynamics of the population renewal process. The risk of intercepting zero is highly dependent on the way the variance of the population size relates to its mean. The minimum population size required for a population not to go extinct can be determined by a scaling equation relating the variance to the arithmetic mean. By the use of a derived expression for the harmonic mean defined by the parameters of the scaling equation we show how it is possible to separate the domains of persistence from those of extinction and to facilitate the identification of populations on the brink of extinction.
This article was reviewed by Mark W. Schwartz (nominated by Peter Olofsson), Josef Bryja (nominated by Aniko Szabo) and Wai-YuanTan. For the full reviews, please go to the Reviewers' Comments section.
Related Articles
Exon definition as a potential negative force against intron losses in evolution
Niu, Deng-Ke
Biology Direct
Previous studies have indicated that the wide variation in intron density (the number of introns per gene) among different eukaryotes largely reflects varying degrees of intron loss during evolution. The most popular model, which suggests that organisms lose introns through a mechanism in which reverse-transcribed cDNA recombines with the genomic DNA, concerns only one mutational force.
Using exons as the units of splicing-site recognition, exon definition constrains the length of exons. An intron-loss event results in fusion of flanking exons and thus a larger exon. The large size of the newborn exon may cause splicing errors, i.e., exon skipping, if the splicing of pre-mRNAs is initiated by exon definition. By contrast, if the splicing of pre-mRNAs is initiated by intron definition, intron loss does not matter. Exon definition may thus be a selective force against intron loss. An organism with a high frequency of exon definition is expected to experience a low rate of intron loss throughout evolution and have a high density of spliceosomal introns.
The majority of spliceosomal introns in vertebrates may be maintained during evolution not because of potential functions, but because of their splicing mechanism (i.e., exon definition). Further research is required to determine whether exon definition is a negative force in maintaining the high intron density of vertebrates.
This article was reviewed by Dr. Scott W. Roy (nominated by Dr. John Logsdon), Dr. Eugene V. Koonin, and Dr. Igor B. Rogozin (nominated by Dr. Mikhail Gelfand). For the full reviews, please go to the Reviewers' comments section.
Related Articles
Unraveling the biochemistry and provenance of pupylation: a prokaryotic analog of ubiquitination
Iyer, Lakshminarayan M
Burroughs, AM
Aravind, L
Biology Direct
Recently Mycobacterium tuberculosis was shown to possess a novel protein modification, in which a small protein Pup is conjugated to the epsilon-amino groups of lysines in target proteins. Analogous to ubiquitin modification in eukaryotes, this remarkable modification recruits proteins for degradation via archaeal-type proteasomes found in mycobacteria and allied actinobacteria. While a mycobacterial protein named PafA was found to be required for this conjugation reaction, its biochemical mechanism has not been elucidated. Using sensitive sequence profile comparison methods we establish that the PafA family proteins are related to the γ-glutamyl-cysteine synthetase and glutamine synthetase. Hence, we predict that PafA is the Pup ligase, which catalyzes the ATP-dependent ligation of the terminal γ-carboxylate of glutamate to lysines, similar to the above enzymes. We further discovered that an ortholog of the eukaryotic PAC2 (e.g. cg2106) is often present in the vicinity of the actinobacterial Pup-proteasome gene neighborhoods and is likely to represent the ancestral proteasomal chaperone. Pup-conjugation is sporadically present outside the actinobacteria in certain lineages, such as verrucomicrobia, nitrospirae, deltaproteobacteria and planctomycetes, and in the latter two lineages it might modify membrane proteins.
This article was reviewed by M. Madan Babu and Andrei Osterman
Related Articles
Synaptic enrichment of microRNAs in adult mouse forebrain is related to structural features of their precursors
Smalheiser, Neil R
Biology Direct
Within mouse forebrain, a subset of microRNAs are significantly enriched in synaptoneurosomes (a synaptic fraction containing pinched-off dendritic spines) and a subset are significantly depleted relative to total forebrain homogenate. Here I show that, as a group, the pre-miR hairpin precursors of synaptically enriched microRNAs exhibit significantly different structural features than those that are non-enriched or depleted. Precursors of synaptically enriched microRNAs tend to have a) shorter uninterrupted double-stranded stem segments, and b) more symmetrical bulges containing a single nucleotide on each side. These structural differences may provide a basis for the differential binding of proteins that mediate dendritic transport of pre-miRs, or that prevent pre-miRs from being prematurely processed into mature miRNAs during the transport process.
This article was reviewed by I. King Jordan and Jerzy Jurka.
Related Articles
Did RNA editing in plant organellar genomes originate under natural selection or through genetic drift?
Jobson, Richard W
Qiu, Yin-Long
Biology Direct
The C↔U substitution types of RNA editing have been observed frequently in organellar genomes of land plants. Although various attempts have been made to explain why such a seemingly inefficient genetic mechanism would have evolved, no satisfactory explanation exists in our view. In this study, we examined editing patterns in chloroplast genomes of the hornwort Anthoceros formosae and the fern Adiantum capillus-veneris and in mitochondrial genomes of the angiosperms Arabidopsis thaliana, Beta vulgaris and Oryza sativa, to gain an understanding of the question of how RNA editing originated.
We found that 1) most editing sites were distributed at the 2nd and 1st codon positions, 2) editing affected codons that resulted in larger hydrophobicity and molecular size changes much more frequently than those with little change involved, 3) editing uniformly increased protein hydrophobicity, 4) editing occurred more frequently in ancestrally T-rich sequences, which were more abundant in genes encoding membrane-bound proteins with many hydrophobic amino acids than in genes encoding soluble proteins, and 5) editing occurred most often in genes found to be under strong selective constraint.
These analyses show that editing mostly affects functionally important and evolutionarily conserved codon positions, codons and genes encoding membrane-bound proteins. In particular, abundance of RNA editing in plant organellar genomes may be associated with disproportionately large percentages of genes in these two genomes that encode membrane-bound proteins, which are rich in hydrophobic amino acids and selectively constrained. These data support a hypothesis that natural selection imposed by protein functional constraints has contributed to selective fixation of certain editing sites and maintenance of the editing activity in plant organelles over a period of more than four hundred millions years. The retention of genes encoding RNA editing activity may be driven by forces that shape nucleotide composition equilibrium in two organellar genomes of these plants. Nevertheless, the causes of lineage-specific occurrence of a large portion of RNA editing sites remain to be determined.
This article was reviewed by Michael Gray (nominated by Laurence Hurst), Kirsten Krause (nominated by Martin Lercher), and Jeffery Mower (nominated by David Ardell).
Related Articles
A new model defines the minimal set of polymorphism in HLA-DQ and -DR that determines susceptibility and resistance to autoimmune diabetes
Parry, Christian S
Brooks, Bernard R
Biology Direct
The mechanism underlying autoimmune diabetes has been difficult to define. There is a strong genetic contribution and numerous studies associate the major histocompatibility complex, especially the class II region, with predisposition or resistance. However, how these molecules are implicated remains obscure.
Presentation of the hypothesis
We have supplemented structural analysis with computational biophysical and sequence analyses and propose an heuristic for distinguishing between human leukocyte antigen molecules that predispose to insulin dependent diabetes mellitus and those that are protective. Polar residues at both β37 and β9 suffice to distinguish accurately between class II alleles that predispose to type 1 diabetes and those that do not. The electrostatic potential within the peptide binding pocket exerts a strong influence on diabetogenic epitopes with basic residues. Diabetes susceptibility alleles are predicted to bind autoantigens strongly with tight affinity, prolonged association and altered cytokine expression profile. Protective alleles bind moderately, and neutral alleles poorly or not at all. Non-Asp β57 is a modifier that supplements disease risk but only in the presence of the polymorphic, polar pair at β9 and β37. The nature of β37 determines resistance on one hand, and susceptibility or dominant protection on the other.
The proposed ideas are illustrated with structural, functional and population studies from the literature. The hypothesis, in turn, rationalizes their results. A plausible mechanism of immune mediated diabetes based on binding affinity and peptide kinetics is discussed. The number of the polymorphic markers present correlates with onset of disease and severity. The molecular elucidation of disease susceptibility and resistance paves the way for risk prediction, treatment and prevention of disease based on analogue peptides.
This article was reviewed by Eugene V. Koonin, Michael Lenardo, Hossam Ashour, and Bhagirath Singh. For the full reviews, please go to the Reviewers' comments section.
Related Articles
Transduplication resulted in the incorporation of two protein-coding sequences into the Turmoil-1 transposable element of C. elegans
Sela, Noa
Stern, Adi
Makalowski, Wojciech
Pupko, Tal
Ast, Gil
Biology Direct
Transposable elements may acquire unrelated gene fragments into their sequences in a process called transduplication. Transduplication of protein-coding genes is common in plants, but is unknown of in animals. Here, we report that the Turmoil-1 transposable element in C. elegans has incorporated two protein-coding sequences into its inverted terminal repeat (ITR) sequences. The ITRs of Turmoil-1 contain a conserved RNA recognition motif (RRM) that originated from the rsp-2 gene and a fragment from the protein-coding region of the cpg-3 gene. We further report that an open reading frame specific to C. elegans may have been created as a result of a Turmoil-1 insertion. Mutations at the 5' splice site of this open reading frame may have reactivated the transduplicated RRM motif.
This article was reviewed by Dan Graur and William Martin. For the full reviews, please go to the Reviewers' Reports section.
Related Articles
Comparable contributions of structural-functional constraints and expression level to the rate of protein sequence evolution
Wolf, Maxim Y
Wolf, Yuri I
Koonin, Eugene V
Biology Direct
Proteins show a broad range of evolutionary rates. Understanding the factors that are responsible for the characteristic rate of evolution of a given protein arguably is one of the major goals of evolutionary biology. A long-standing general assumption used to be that the evolution rate is, primarily, determined by the specific functional constraints that affect the given protein. These constrains were traditionally thought to depend both on the specific features of the protein's structure and its biological role. The advent of systems biology brought about new types of data, such as expression level and protein-protein interactions, and unexpectedly, a variety of correlations between protein evolution rate and these variables have been observed. The strongest connections by far were repeatedly seen between protein sequence evolution rate and the expression level of the respective gene. It has been hypothesized that this link is due to the selection for the robustness of the protein structure to mistranslation-induced misfolding that is particularly important for highly expressed proteins and is the dominant determinant of the sequence evolution rate.
This work is an attempt to assess the relative contributions of protein domain structure and function, on the one hand, and expression level on the other hand, to the rate of sequence evolution. To this end, we performed a genome-wide analysis of the effect of the fusion of a pair of domains in multidomain proteins on the difference in the domain-specific evolutionary rates. The mistranslation-induced misfolding hypothesis would predict that, within multidomain proteins, fused domains, on average, should evolve at substantially closer rates than the same domains in different proteins because, within a mutlidomain protein, all domains are translated at the same rate. We performed a comprehensive comparison of the evolutionary rates of mammalian and plant protein domains that are either joined in multidomain proteins or contained in distinct proteins. Substantial homogenization of evolutionary rates in multidomain proteins was, indeed, observed in both animals and plants, although highly significant differences between domain-specific rates remained. The contributions of the translation rate, as determined by the effect of the fusion of a pair of domains within a multidomain protein, and intrinsic, domain-specific structural-functional constraints appear to be comparable in magnitude.
Fusion of domains in a multidomain protein results in substantial homogenization of the domain-specific evolutionary rates but significant differences between domain-specific evolution rates remain. Thus, the rate of translation and intrinsic structural-functional constraints both exert sizable and comparable effects on sequence evolution.
This article was reviewed by Sergei Maslov, Dennis Vitkup, Claus Wilke (nominated by Orly Alter), and Allan Drummond (nominated by Joel Bader). For the full reviews, please go to the Reviewers' Reports section.
Related Articles
A new family of polymerases related to superfamily A DNA polymerases and T7-like DNA-dependent RNA polymerases
Iyer, Lakshminarayan M
Abhiman, Saraswathi
Aravind, L
Biology Direct
Using sequence profile methods and structural comparisons we characterize a previously unknown family of nucleic acid polymerases in a group of mobile elements from genomes of diverse bacteria, an algal plastid and certain DNA viruses, including the recently reported Sputnik virus. Using contextual information from domain architectures and gene-neighborhoods we present evidence that they are likely to possess both primase and DNA polymerase activity, comparable to the previously reported prim-pol proteins. These newly identified polymerases help in defining the minimal functional core of superfamily A DNA polymerases and related RNA polymerases. Thus, they provide a framework to understand the emergence of both DNA and RNA polymerization activity in this class of enzymes. They also provide evidence that enigmatic DNA viruses, such as Sputnik, might have emerged from mobile elements coding these polymerases.
This article was reviewed by Eugene Koonin and Mark Ragan.
Related Articles
CAIcal: A combined set of tools to assess codon usage adaptation
Puigbò, Pere
Bravo, Ignacio G
Garcia-Vallve, Santiago
Biology Direct
The Codon Adaptation Index (CAI) was first developed to measure the synonymous codon usage bias for a DNA or RNA sequence. The CAI quantifies the similarity between the synonymous codon usage of a gene and the synonymous codon frequency of a reference set.
We describe here CAIcal, a web-server available at that includes a complete set of utilities related with the CAI. The server provides useful important features, such as the calculation and graphical representation of the CAI along either an individual sequence or a protein multiple sequence alignment translated to DNA. The automated calculation of CAI and its expected value is also included as one of the CAIcal tools. The software is also free to be downloaded as a standalone application for local use.
The CAIcal server provides a complete set of tools to assess codon usage adaptation and to help in genome annotation.
This article was reviewed by Purificación López-García, Dan Graur, Rob Knight and Shamil Sunyaev.
Related Articles
An extension of the coevolution theory of the origin of the genetic code
Di Giulio, Massimo
Biology Direct
The coevolution theory of the origin of the genetic code suggests that the genetic code is an imprint of the biosynthetic relationships between amino acids. However, this theory does not seem to attribute a role to the biosynthetic relationships between the earliest amino acids that evolved along the pathways of energetic metabolism. As a result, the coevolution theory is unable to clearly define the very earliest phases of genetic code origin. In order to remove this difficulty, I here suggest an extension of the coevolution theory that attributes a crucial role to the first amino acids that evolved along these biosynthetic pathways and to their biosynthetic relationships, even when defined by the non-amino acid molecules that are their precursors.
It is re-observed that the first amino acids to evolve along these biosynthetic pathways are predominantly those codified by codons of the type GNN, and this observation is found to be statistically significant. Furthermore, the close biosynthetic relationships between the sibling amino acids Ala-Ser, Ser-Gly, Asp-Glu, and Ala-Val are not random in the genetic code table and reinforce the hypothesis that the biosynthetic relationships between these six amino acids played a crucial role in defining the very earliest phases of genetic code origin.
All this leads to the hypothesis that there existed a code, GNS, reflecting the biosynthetic relationships between these six amino acids which, as it defines the very earliest phases of genetic code origin, removes the main difficulty of the coevolution theory. Furthermore, it is here discussed how this code might have naturally led to the code codifying only for the domains of the codons of precursor amino acids, as predicted by the coevolution theory. Finally, the hypothesis here suggested also removes other problems of the coevolution theory, such as the existence for certain pairs of amino acids with an unclear biosynthetic relationship between the precursor and product amino acids and the collocation of Ala between the amino acids Val and Leu belonging to the pyruvate biosynthetic family, which the coevolution theory considered as belonging to different biosyntheses.
This article was reviewed by Rob Knight, Paul Higgs (nominated by Laura Landweber), and Eugene Koonin.
Related Articles
Same-strand overlapping genes in bacteria: compositional determinants of phase bias
Sabath, Niv
Graur, Dan
Landan, Giddy
Biology Direct
Same-strand overlapping genes may occur in frameshifts of one (phase 1) or two nucleotides (phase 2). In previous studies of bacterial genomes, long phase-1 overlaps were found to be more numerous than long phase-2 overlaps. This bias was explained by either genomic location or an unspecified selection advantage. Models that focused on the ability of the two genes to evolve independently did not predict this phase bias. Here, we propose that a purely compositional model explains the phase bias in a more parsimonious manner. Same-strand overlapping genes may arise through either a mutation at the termination codon of the upstream gene or a mutation at the initiation codon of the downstream gene. We hypothesized that given these two scenarios, the frequencies of initiation and termination codons in the two phases may determine the number for overlapping genes.
We examined the frequencies of initiation- and termination-codons in the two phases, and found that termination codons do not significantly differ between the two phases, whereas initiation codons are more abundant in phase 1. We found that the primary factors explaining the phase inequality are the frequencies of amino acids whose codons may combine to form start codons in the two phases. We show that the frequencies of start codons in each of the two phases, and, hence, the potential for the creation of overlapping genes, are determined by a universal amino-acid frequency and species-specific codon usage, leading to a correlation between long phase-1 overlaps and genomic GC content.
Our model explains the phase bias in same-strand overlapping genes by compositional factors without invoking selection. Therefore, it can be used as a null model of neutral evolution to test selection hypotheses concerning the evolution of overlapping genes.
This article was reviewed by Bill Martin, Itai Yanai, and Mikhail Gelfand.
Related Articles
Critical role for BIM in T cell receptor restimulation-induced death
Snow, Andrew L
Oliveira, João B
Zheng, Lixin
Dale, Janet K
Fleisher, Thomas A
Lenardo, Michael J
Biology Direct
Upon repeated or chronic antigen stimulation, activated T cells undergo a T cell receptor (TCR)-triggered propriocidal cell death important for governing the intensity of immune responses. This is thought to be chiefly mediated by an extrinsic signal through the Fas-FasL pathway. However, we observed that TCR restimulation still potently induced apoptosis when this interaction was blocked, or genetically impaired in T cells derived from autoimmune lymphoproliferative syndrome (ALPS) patients, prompting us to examine Fas-independent, intrinsic signals.
Upon TCR restimulation, we specifically noted a marked increase in the expression of BIM, a pro-apoptotic Bcl-2 family protein known to mediate lymphocyte apoptosis induced by cytokine withdrawal. In fact, T cells from an ALPS type IV patient in which BIM expression is suppressed were more resistant to restimulation-induced death. Strikingly, knockdown of BIM expression rescued normal T cells from TCR-induced death to as great an extent as Fas disruption.
Our data implicates BIM as a critical mediator of apoptosis induced by restimulation as well as growth cytokine withdrawal. These findings suggest an important role for BIM in eliminating activated T cells even when IL-2 is abundant, working in conjunction with Fas to eliminate chronically stimulated T cells and maintain immune homeostasis.
This article was reviewed by Dr. Wendy Davidson (nominated by Dr. David Scott), Dr. Mark Williams (nominated by Dr. Neil Greenspan), and Dr. Laurence C. Eisenlohr.
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A nitty-gritty aspect of correlation and network inference from gene expression data
Klebanov, Lev B
Yakovlev, Andrei Yu
Biology Direct
All currently available methods of network/association inference from microarray gene expression measurements implicitly assume that such measurements represent the actual expression levels of different genes within each cell included in the biological sample under study. Contrary to this common belief, modern microarray technology produces signals aggregated over a random number of individual cells, a "nitty-gritty" aspect of such arrays, thereby causing a random effect that distorts the correlation structure of intra-cellular gene expression levels.
This paper provides a theoretical consideration of the random effect of signal aggregation and its implications for correlation analysis and network inference. An attempt is made to quantitatively assess the magnitude of this effect from real data. Some preliminary ideas are offered to mitigate the consequences of random signal aggregation in the analysis of gene expression data.
Resulting from the summation of expression intensities over a random number of individual cells, the observed signals may not adequately reflect the true dependence structure of intra-cellular gene expression levels needed as a source of information for network reconstruction. Whether the reported effect is extrime or not, the important point, is to reconize and incorporate such signal source for proper inference. The usefulness of inference on genetic regulatory structures from microarray data depends critically on the ability of investigators to overcome this obstacle in a scientifically sound way.
This article was reviewed by Byung Soo KIM, Jeanne Kowalski and Geoff McLachlan
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The evolution of strand preference in simulated RNA replicators with strand displacement: Implications for the origin of transcription
Takeuchi, Nobuto
Salazar, Laura
Poole, Anthony M
Hogeweg, Paulien
Biology Direct
The simplest conceivable example of evolving systems is RNA molecules that can replicate themselves. Since replication produces a new RNA strand complementary to a template, all templates would eventually become double-stranded and, hence, become unavailable for replication. Thus the problem of how to separate the two strands is considered a major issue for the early evolution of self-replicating RNA. One biologically plausible way to copy a double-stranded RNA is to displace a preexisting strand by a newly synthesized strand. Such copying can in principle be initiated from either the (+) or (-) strand of a double-stranded RNA. Assuming that only one of them, say (+), can act as replicase when single-stranded, strand displacement produces a new replicase if the (-) strand is the template. If, however, the (+) strand is the template, it produces a new template (but no replicase). Modern transcription exhibits extreme strand preference wherein anti-sense strands are always the template. Likewise, replication by strand displacement seems optimal if it also exhibits extreme strand preference wherein (-) strands are always the template, favoring replicase production. Here we investigate whether such strand preference can evolve in a simple RNA replicator system with strand displacement.
We first studied a simple mathematical model of the replicator dynamics. Our results indicated that if the system is well-mixed, there is no selective force acting upon strand preference per se. Next, we studied an individual-based simulation model to investigate the evolution of strand preference under finite diffusion. Interestingly, the results showed that selective forces "emerge" because of finite diffusion. Strikingly, the direction of the strand preference that evolves [i.e. (+) or (-) strand excess] is a complex non-monotonic function of the diffusion intensity. The mechanism underlying this behavior is elucidated. Furthermore, a speciation-like phenomenon is observed under certain conditions: two extreme replication strategies, namely replicase producers and template producers, emerge and coexist among competing replicators.
Finite diffusion enables the evolution of strand preference, the direction of which is a non-monotonic function of the diffusion intensity. By identifying the conditions under which strand preference evolves, this study provides an insight into how a rudimentary transcription-like pattern might have emerged in an RNA-based replicator system.
This article was reviewed by Eugene V Koonin, Rob Kinght and István Scheuring (nominated by David H Ardell). For the full reviews, please go to the Reviewers' comments section.
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A highly conserved family of inactivated archaeal B family DNA polymerases
Rogozin, Igor B
Makarova, Kira S
Pavlov, Youri I
Koonin, Eugene V
Biology Direct
A widespread and highly conserved family of apparently inactivated derivatives of archaeal B-family DNA polymerases is described. Phylogenetic analysis shows that the inactivated forms comprise a distinct clade among archaeal B-family polymerases and that, within this clade, Euryarchaea and Crenarchaea are clearly separated from each other and from a small group of bacterial homologs. These findings are compatible with an ancient duplication of the DNA polymerase gene followed by inactivation and parallel loss in some of the lineages although contribution of horizontal gene transfer cannot be ruled out. The inactivated derivative of the archaeal DNA polymerase could form a complex with the active paralog and play a structural role in DNA replication.
This article was reviewed by Purificacion Lopez-Garcia and Chris Ponting. For the full reviews, please go to the Reviewers' Reports section.
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Origin of the nucleus and Ran-dependent transport to safeguard ribosome biogenesis in a chimeric cell
Jékely, Gáspár
Biology Direct
The origin of the nucleus is a central problem about the origin of eukaryotes. The common ancestry of nuclear pore complexes (NPC) and vesicle coating complexes indicates that the nucleus evolved via the modification of a pre-existing endomembrane system. Such an autogenous scenario is cell biologically feasible, but it is not clear what were the selective or neutral mechanisms that had led to the origin of the nuclear compartment.
A key selective force during the autogenous origin of the nucleus could have been the need to segregate ribosome factories from the cytoplasm where ribosomal proteins (RPs) of the protomitochondrium were synthesized. After its uptake by an anuclear cell the protomitochondrium transferred several of its RP genes to the host genome. Alphaproteobacterial RPs and archaebacterial-type host ribosomes were consequently synthesized in the same cytoplasm. This could have led to the formation of chimeric ribosomes. I propose that the nucleus evolved when the host cell compartmentalised its ribosome factories and the tightly linked genome to reduce ribosome chimerism. This was achieved in successive stages by first evolving karyopherin and RanGTP dependent chaperoning of RPs, followed by the evolution of a membrane network to serve as a diffusion barrier, and finally a hydrogel sieve to ensure selective permeability at nuclear pores. Computer simulations show that a gradual segregation of cytoplasm and nucleoplasm via these steps can progressively reduce ribosome chimerism.
Ribosome chimerism can provide a direct link between the selective forces for and the mechanisms of evolving nuclear transport and compartmentalisation. The detailed molecular scenario presented here provides a solution to the gradual evolution of nuclear compartmentalization from an anuclear stage.
This article was reviewed by Eugene V Koonin, Martijn Huynen, Anthony M. Poole and Patrick Forterre.
Related Articles
The Last Universal Common Ancestor: emergence, constitution and genetic legacy of an elusive forerunner
Glansdorff, Nicolas
Xu, Ying
Labedan, Bernard
Biology Direct
Since the reclassification of all life forms in three Domains (Archaea, Bacteria, Eukarya), the identity of their alleged forerunner (Last Universal Common Ancestor or LUCA) has been the subject of extensive controversies: progenote or already complex organism, prokaryote or protoeukaryote, thermophile or mesophile, product of a protracted progression from simple replicators to complex cells or born in the cradle of "catalytically closed" entities? We present a critical survey of the topic and suggest a scenario.
LUCA does not appear to have been a simple, primitive, hyperthermophilic prokaryote but rather a complex community of protoeukaryotes with a RNA genome, adapted to a broad range of moderate temperatures, genetically redundant, morphologically and metabolically diverse. LUCA's genetic redundancy predicts loss of paralogous gene copies in divergent lineages to be a significant source of phylogenetic anomalies, i.e. instances where a protein tree departs from the SSU-rRNA genealogy; consequently, horizontal gene transfer may not have the rampant character assumed by many. Examining membrane lipids suggest LUCA had sn1,2 ester fatty acid lipids from which Archaea emerged from the outset as thermophilic by "thermoreduction," with a new type of membrane, composed of sn2,3 ether isoprenoid lipids; this occurred without major enzymatic reconversion. Bacteria emerged by reductive evolution from LUCA and some lineages further acquired extreme thermophily by convergent evolution. This scenario is compatible with the hypothesis that the RNA to DNA transition resulted from different viral invasions as proposed by Forterre. Beyond the controversy opposing "replication first" to metabolism first", the predictive arguments of theories on "catalytic closure" or "compositional heredity" heavily weigh in favour of LUCA's ancestors having emerged as complex, self-replicating entities from which a genetic code arose under natural selection.
Life was born complex and the LUCA displayed that heritage. It had the "body "of a mesophilic eukaryote well before maturing by endosymbiosis into an organism adapted to an atmosphere rich in oxygen. Abundant indications suggest reductive evolution of this complex and heterogeneous entity towards the "prokaryotic" Domains Archaea and Bacteria. The word "prokaryote" should be abandoned because epistemologically unsound.
This article was reviewed by Anthony Poole, Patrick Forterre, and Nicolas Galtier.
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text:
- Report: #175521
Report - Rebuttal - Arbitrate
Complaint Review: USSA - LVNAAP
USSA - LVNAAPP.o. Box 98835 Las Vegas, Nevada U.S.A.
USSA - LVNAAP - NBPI ripoff Las Vegas Nevada
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You will not receive any money from them no matter what you are promised! DON'T SEND THEM MONEY! Don't fall for it. I have recieved 13 letters from them as of 2/11/06. I just keep writing STOP SENDING an them and I mail them back. Like a said before the have to pay the postage.
If enough people around the country would do this, we may be able to make it stop! BUT if you keep sending them money millions of other good honest citizens will loose more and more money, that we could be donating to charity and needy families, churches and other good, honest people in our communities!
With all that said, let's make them pay for thier mistake and not pay them for ours!! Thanks for your time and GOOD LUCK!
lawrenceville, Georgia
This report was posted on Ripoff Report on 02/09/2006 12:54 PM and is a permanent record located here: http://www.ripoffreport.com/r/USSA-LVNAAP/Las-Vegas-Nevada-89195/USSA-LVNAAP-NBPI-ripoff-Las-Vegas-Nevada-175521. The posting time indicated is Arizona local time. Arizona does not observe daylight savings so the post time may be Mountain or Pacific depending on the time of year.
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—Julie Otsuka, author of The Buddha in the Attic
"Rarely does a cast of beloved literary figures from another culture and time come alive on the pages of a modern writer's work. Pauline Chen has reimagined the characters from my very favorite novel to make a compelling new version of China's great literary masterpiece. I highly recommend The Red Chamber. It will transport you into an altogether new world."
—Arthur Golden, author of Memoirs of a Geisha
"In Pauline Chen's transporting interpretation of the Chinese classic The Dream of the Red Chamber, the byzantine machinations and behind-the-screen politics of the Jia family are so skillfully rendered as to bring to mind a delicate ink painting suddenly and vividly brought to life. A remarkable achievement."
—Janice Lee, author of The Piano Teacher
"The Red Chamber draws a memorable portrait of the Qing dynasty era, revealing a dangerous world of intrigue and secrets within the entrapping web of societal mores and manners. Written in a precise, cinematic style, Chen's novel brings this fascinating historical period to vivid life."
—Dan Chaon, author of Stay Awake
"Fans of historical fiction who appreciate resonant details, unexpected intrigue, and multigenerational plotting will find this work irresistible. With just the right blend of the highbrow literary and guilty summer pulp, Chen just might put this 18th-century classic on 21st-century bestseller lists."
—Library Journal
"A vivid portrait…From the mighty heights to the depths of poverty and despair, the significance of female relationships, friendships, and rivalries are at the forefront of this compelling glimpse into an exotic time and place."
"A vivid, lively reimagining…Despite their Eastern origins, Chen's engaging heroines seem like direct descendants of the doomed, repressed women of classic Western literature."
—Book Page
"Leisurely…supple…Chen often touches notes of emotional depth."
—Kirkus Reviews
"Ambitious and exquisite…utterly absorbing…sure to astound and enthrall readers up until the very last page. The Red Chamber reads like a Chinese Downton Abbey and is a fitting homage to a beloved masterpiece."
—Tribute Books
"The excesses of Imperial China frame this elegant story of shifting fortunes, power struggles, palace intrigue, betrayal, and love…The Red Chamber takes a long hard look at the complex interconnected desires, ambitions, and conventions that can bind a family together—or tear it apart."
—The Daily Beast, "Hot Reads"
"Moving, startling, and quite beautiful…a welcome, memorable introduction to characters vivid in the imaginations of generations of Chinese readers."
—Cleveland Plain Dealer
"Compelling…intricate…thoughtful and provocative…No doubt Chen has provided us with a work that will not only be found on the list of historical classics but also become a part of the lexicon of the greatest love stories in the world."
"Here is clearly a work of love and a pleasing introduction to a novel—and a world—that Americans deserve to get to know."
—The Columbus Dispatch
"The Red Chamber offers a window into a foreign world…Chen's framework provides a context for her characters' actions, as often flawed as they are heroic, that makes things not just knowable but comprehensible."
—The Denver Post
"Full of lavish details of the palace, sumptuous feasts, and day-day minutiae, levitating whispered conversations overheard by the wrong parties, capricious scheming between family members, and gossip hidden beneath every elegant tapestry and beaded pillow to lofted heights…There's much to do about more serious matters, too—especially in the latter half of the novel, when political unrest in Beijing threatens to destroy the family's tenuous hierarchy."
—Publishers Weekly
"Bold and memorable…Chen retells and recreates in lush detail the daily life inside the Rongguo Mansion, where scandalous secrets and lies are hidden behind a grand façade."
—Chicago Tribune
New York Daily News Summer 2012 Must-Reads


text:
On 10/22/12 23:04, Eric Blake wrote:
* .gnulib: Update to latest, prior to freeze. --- Gnulib has been relatively quiet since our last update, and I'm not sure whether any of these patches directly impact us, but it can't hurt to have the latest going into a freeze for 1.0.0.
Shouldn't hurt. ACK. Peter


text:
We start of at the back, and it's not other than Newcastle and Holland goal-keeper Tim Krul.
Priced at only £4.5m in the Official Fantasy Premier League game, the Toon shot-stopper already amassed a clean sheet last weekend and is set to go on a run of decent fixtures… starting with a visit from an out-of-sorts Crystal Palace.
If he keeps another clean-sheet at St.Jame's Park against the Eagles this weekend, then his modest £4.5 price tag is bound to rise over the course of the next few game-weeks.


text: Is it possible to change the event page format so that my custom content appears first, followed by the event details & map generated by Events Manager? I'd like to have an image, then my custom content, and then the details. Right now it shows Events Manager's details first, then my custom content.


text:
- Report: #339924
Report - Rebuttal - Arbitrate
Complaint Review: AM PM Diet
AM PM Dietwww.AMPMdiet.net Internet U.S.A.
AM PM Diet JUST ANOTHER DIET SCAM!!! Www.ampmdiet.com Internet
*REBUTTAL Owner of company: AmPmDiet.com
*REBUTTAL Owner of company: Am Pm Diet www.AmPmDiet.com
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I am going to have my account changed so they cannot charge anymore. I don't have $170 lying aroung for them to take and try to get it back later.
Ticked off
Athens, Illinois
This report was posted on Ripoff Report on 06/13/2008 08:41 AM and is a permanent record located here: http://www.ripoffreport.com/r/AM-PM-Diet/internet/AM-PM-Diet-JUST-ANOTHER-DIET-SCAM-Wwwampmdietcom-Internet-339924. The posting time indicated is Arizona local time. Arizona does not observe daylight savings so the post time may be Mountain or Pacific depending on the time of year.
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#1 REBUTTAL Owner of company
AUTHOR: felixborin - (United States of America)
SUBMITTED: Saturday, December 17, 2011POSTED: Saturday, December 17, 2011
I have nothing to do or in no way related or associated with AmPmDiet.net ( .net).
My website www.AmPmDiet.com is a legitimate business and has never ripped off anyone.
Are you an owner, employee or ex-employee with either negative or positive information about the company or individual, or can you provide "insider information" on this company?
#2 REBUTTAL Owner of company
Am Pm Diet www.AmPmDiet.com
AUTHOR: felixborin - (United States of America)
SUBMITTED: Tuesday, February 23, 2010POSTED: Tuesday, February 23, 2010
I own the domain name www.AmPmDiet.com
I have never sold anything using this domain. It's just a domain name I have owned for a few years. I never done any business or ripped any one off with it. I think it is being confused with a(.net ) domain.
Are you an owner, employee or ex-employee with either negative or positive information about the company or individual, or can you provide "insider information" on this company?
Advertisers above have met our
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text:
You've arrived…
In your own journey of the spirit, you've come upon the site of a community of people who have found that the path of following Jesus offers our lives wholeness, meaning, and challenge to live differently.
Is this what you have been looking for?
Then explore a little further…
You are welcome here.
This site is optimized for mobile devices.
If you do not see graphics and photos on this page,
please click on "View Full Site" below.
(Click on event images to find out more information.)


text:
- Report: #1053172
Report - Rebuttal - Arbitrate
Complaint Review: RPG Art Gallery Inc
RPG Art Gallery Inc1787 Whitehall Forest Ct Atlanta, Georgia USA
RPG Art Gallery Inc Personal assistant Atlanta Georgia
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I rec'd a cashiers check from this person and will not be putting it into my account thx to your site.
BUT this check is payable at SUNTRUST Bank ($1,970.00).
Whats to keep me from going to Suntrust and just cashing it and keeping the money?
THX in advance
This report was posted on Ripoff Report on 05/22/2013 11:21 PM and is a permanent record located here: http://www.ripoffreport.com/r/RPG-Art-Gallery-Inc/Atlanta-Georgia-30316/RPG-Art-Gallery-Inc-Personal-assistant-Atlanta-Georgia-1053172. The posting time indicated is Arizona local time. Arizona does not observe daylight savings so the post time may be Mountain or Pacific depending on the time of year.
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Change Location
ACE Fit Share
Add some variety to your fitness routine with these upper and lower leg exercises from The American Council on Exercise. We have a large selection of leg exercises that will will help you strengthen and build muscle throughout your legs including your hamstrings, thighs, shin and calf muscles. Start taking advantage of this free information today! If you are looking for full workout routines that incorporate these leg exercises, check out our Workouts section.
Fit Life Articles
"Carbohydrates make you gain weight." This is one of the many diet myths that abound these days, fueled by food marketing and the diet industry. But what's really behind these myths? The simplest explanation is usually closest to the truth, and this applies to nutrition,...
Learning how to do two classic foundational exercises—the push-up and the hip hinge—can help you build get fit, strong and flexible for life. Begin by mastering these two oldies but goodies, watch your strength, fitness and flexibility skyrocket while you avoid injuries.
When it comes to grocery shopping, it's a good idea to stick to the perimeter of the store. That's where you'll find the healthiest, freshest foods. You can certainly find healthy options in a store's interior as well—just make sure you read the labels so you know what...


text:
|Sailing Master
|25th at MIT
|Previous College:
|Tufts University
Fran Charles joined the Institute in 1992 as a varsity sailing coach and assistant to former sailing master, Hatch Brown. Now, as the fourth Sailing Master since 1935, Charles is responsible for the entire recreational sailing program with over 2,000 members annually developing sailing skills and using the fleet of over 100 boats.
In 2007, Charles was inducted into the Inter-Collegiate Sailing Association (ICSA) Hall of Fame and received the Graham Hall Award for Distinguished Service to College Sailing by a Professional. He is a certified umpire for team racing and is often volunteering to officiate at US National and World Championships. Charles's race management skills are sought for junior, national and world level events year in and year out.
Before joining MIT, Charles served as co-director of the Courageous Sailing Center in Boston, which teaches sailing to city children. In 1996 and 1997, he managed the sailing competition for the Massachusetts Special Olympics as well as sponsored multiple clinics, seminars, and competitions for local junior sailors. In 1999, Charles was honored by Mass Bay Sailing with its "Distinguished Service to Yachting" Award.
Charles and his wife, Sue, continue to race competitively together on the winter "frostbite circuits" in New England. Occasionally he competes in the Olympic Star Class and IOD Fleets in Marblehead and Northeast Harbor.
|Head Coach
|9th at MIT
|Previous College:
|Queen's University (Canada) '97
Following a hiatus from intercollegiate coaching, Mike Kalin returned to the MIT sailing program in 2014. He was previously a coach with the Engineers from 2000-06, helping the coed team to a consistent ranking among the top 15 in the nation, with the squad placing as high as 11th at Nationals.
Kalin left MIT to compete full-time for the Canadian Sailing Team where he was the fourth-ranked member of the team in the Olympic Laser class, winning the Marvin McDill Award in 2006 for the top rookie performance at an Olympic class world championship. Since sailing for the Canadian team he served as the sailing director at the St. Francis Yacht Club in San Francisco from 2008-11 as well as working as a coach for the U.S. Olympic Sailing Team and as a member of the 2013 America's Cup Race Management Group.
|Head Coach
|11th at MIT
|Previous College:
|St. Mary's College (Md.) '99
Matt Lindblad enters his 11th season at MIT. During his tenure in Cambridge, he helped guide the Engineers to eighth place at the 2016 ICSA Women's National Championship, fifth place at the 2013 ICSA Women's National Championship and sixth place at the 2008 ICSA Dinghy National Championship.
Under his leadership, RWU became a nationally recognized program with regular finishes in the Sailing World Top 20 National Rankings as well as top finishes at National level events. Lindblad has also enjoyed success as a competitor. In September, 2005, Lindblad competed for the Grey Goose Team Racing World Championship, winning the Team Racing World Championship with USA 1 (Cape Cod Whishbone). Lindblad also won the US Team Racing National Championships (Hinman Trophy) in 2003 and 2004 with Cape Cod Whishbone.
As an undergraduate, Lindblad was a four-year varsity letter winner at the national powerhouse St. Mary's College of Maryland. He was a team captain for the 1999 St. Mary's Seahawks squad, which won the 1999 Collegiate Team Racing National Championships and finished second in Fleet Racing National Championships among other victories. Lindblad has demonstrated his passion for coaching sailing in various capacities since assuming his first post in 1993. While working and going to school in Connecticut after college, he volunteered as an assistant coach for Fitch and Stonington High Schools in Southern Connecticut.
During the summer, Lindblad was the Waterfront Director at Ida Lewis YC in Newport (2003-04) and Advanced Racing Coach at Sail Newport (2005). He served as the Head Instructor/Racing Coach at Ram Island YC in Noank, Conn., from 1993-1998. Lindblad's other sailing successes include wins at Team Racing Mid-Winters (V-15) in 2005, The Newport Regatta (J24) in 2003 and 2005, and the J24 Fleet 50 Season honors in 2004 and 2005. Lindblad has also achieved top-five finishes at V-15 Nationals in 1998 (fifth) and 2000 (second) and is active in the Newport Laser Frostbiting fleet.


text:
Share the post "Connecticut Boxing Hall of Fame Induction Dinner Rescheduled for Nov. 17"
UNCASVILLE, Conn. (September 5, 2012) – The 8th annual Connecticut Boxing Hall of Fame (CBHOF) Gala Induction Dinner has been rescheduled for November 17, one week after the original date, in the Uncas Ballroom at Mohegan Sun.
The 2012 CBHOF inductees are former World Boxing Association (WBA) light middleweight champion "Tremendous" Travis Simms, former World Boxing Union (WBU) middleweight titlist "Dangerous" Dana Rosenblatt, five-time Trainer of the Year Freddie Roach, promoter Jimmy Burchfield (Classic Entertainment and Sports, Inc.), manager George Cruz and the late manager/promoter Lou Viscusi.
Tickets for the 8th annual CBHOF Gala Induction Dinner, reasonably priced at $75.00, are on sale now by calling Kim Baker at Mohegan Sun (1.860-.862.7377) or Sherman Cain at the Manchester Journal Inquirer (1.800.237.3606 X321). Doors open at 5:30 p.m. ET, cocktails at 6 p.m. ET, followed by dinner.
Go online to www.ctboxinghof.com for additional information about the CBHOF.


text:
I know TheBrickster has a soft spot for all things Western and all things Train, this should check both boxes.
Inspired by the 1874 Monterey & Salinas Combo currently on display at the California State Railroad Museum in Sacramento.
More photos on flickr
Edited by TheBrickster, 26 March 2010 - 02:12 PM.


text:
I've got 2 wordpress blogs, same version, one domain and one sub-domain.
I've change nothing on them but, since 5 days now, I've got no stats on one of them... No error message, all seems right. Piwik is OK, because I've got the stats for the other blog.
I've de install and re install, but nothing change.
What could I do please ?
Very cordially,
ANDRE Ani


text:
Skip to comments.Barack Obama faces 30 death threats a day, stretching US Secret Service
Posted on 08/03/2009 8:49:17 PM PDT by Nachum
Since Mr Obama took office, the rate of threats against the president has increased 400 per cent from the 3,000 a year or so under President George W. Bush, according to Ronald Kessler, author of In the President's Secret Service.
Some threats to Mr Obama, whose Secret Service codename is Renegade, have been publicised, including an alleged plot by white supremacists in Tennessee late last year to rob a gun store, shoot 88 black people, decapitate another 14 and then assassinate the first black president in American history.
(Excerpt) Read more at telegraph.co.uk ...
Those are just the 30 threats per day. Then the night shift comes on.
Man, don't ya know mrs obammy has a big ole shelf ass?
No, I don't. I hadn't heard about that.
That really happened?
Of course not and I doubt that the vast majority of congress could either.
I'd really like candidates to have to undergo rigorous background checks before each election and random drug testing once elected.
And no keeping the results secret!
I havent seen any pictures. I wont believe it until I see picutres.
From what I have heard, that is SOP for the Secret Service guarding the presidential motorcade now. Yes, it is menacing, but I figure they are the experts are presidential security. Maybe things have changed since 9/11.
On Bush's watch...never heard or saw it. Anyone?
Let's hope he never crosses the river Styxx
Remember 30 reports a day includes threats by incarcerated prisoners and psychiatrically impaired people. Lots of these people are already locked up and are checked out by the agency. And you can bet that they are not all white.
Excellent suggestions.
An institutional sense of humor? 1. They call former US Senator obama, "Mr obama", avoiding the title that the druggie in our White House is trying to usurp. 2. "Renegade" and "Traitor" are nearly equivalent in meaning. If I find the agent who chose that nickname for the socialist, I'll buy him a beer.
renegade (noun): traitor, betrayer, turncoat, deceiver, squealer, rat
"Instead of bringing in more agents - instantly identifiable because of their bulky suits, worn over bullet-proof jackets, and earpieces - the Secret Service directed agents to work longer hours to cover the extra load and to miss firearms training, physical fitness sessions and tests."
That doesn't surprise me. Nor would it surprise me to see the agents ballooning up. Have you seen recent pix of the boys in ATF? Many are looking real fat and would probably keel over from strokes if they had to run 50 yards.
I'd also guess that the average IQ at the SS has fallen 20 points or more in the past 10 years.
The Washington DC party and loot culture is attracting the dregs of society. I know some of these Marxist federal bureaucrats and they're foul-mouthed, fat morons, spouting trash like "BUSHISHITLER!!!"
Why would anyone want him dead? I mean, he's doing a GREAT job at killing the Democratic party and left-wing ideals.
While Obama is not on my Top Ten List (bottom of the Bottom 10—maybe), woe to anyone who tries to do something stupid.
The Secret Service is charged with protecting the President of the United States regardless of who occupies the Oval Office. That is how it should be. The Office is bigger than the man. It might not seem like that now, but this too, shall pass either through the ballot box in 4 years or the end of his 2nd term in 8.
It's our job to ensure the ballot box in 4, LOL!
88 is claimed to be one of those symbolic numbers that Nazi gay fanatasists like those two losers took seriously
I wonder how many of these threats come from people who voted for him and realize now they were ripped off...
President Bush was the only President to ever have a movie made about being assassinated. Remember the "Assassins wanted" ads that were on the I'net?
"I was driving east on the freeway and noticed that there were no cars on the other side of the freeway. Then I remembered that Bush was coming to town for something or other, and judging by the cops on all the overpasses, I figured this was why no one was on the freeway. I pulled off near the Gateway Transit Center to watch, as many people already were. This Presidential motorcade was a lot longer and more incredible than the one I had previously witnessed downtown. First, about 5 motorcycle cops cruised down the freeway way ahead of the motorcade, then probably about 7-10 normal cops, followed by about 3 suvs with guys hanging out of the back with guns, followed by 3 Presidential limousines (with two flags on either side of the front of the limousine), followed by pretty much the mirror image of what had just preceded them. In addition, there were a few ambulances trailing the entire thing. It was really pretty crazy. I can't imagine living in Washington, DC if this kind of thing has to interrupt traffic all the time. Must be nice to be the President and never have to worry about traffic (well, and all the other perks.)" - link
"What you can't see in that photo is that there are dudes with machine guns in the back of the suv's. Was crossing the street here in NYC a few years ago when Cheney's motorcade went by and I was trying to jaywalk behind and secret service dudes in the open back of SUV aimed there guns at me, that'll teach me not to jaywalk." - link
Since the president is starting to backtrack on his no taxes pledge, wouldn't it be more appropriate if his SS code name was "Reneger" rather than "Renegade"?
They're ready for Obama care!
"Id also guess that the average IQ at the SS has fallen 20 points or more in the past 10 years."
Who the hell would want to give their life for this trash? I sure wouldn't!
"The Washington DC party and loot culture is attracting the dregs of society. I know some of these Marxist federal bureaucrats and theyre foul-mouthed, fat morons, spouting trash like BUSHISHITLER!!!"
Of course! We'll probably get a "gay Gestapo" soon. They're so enamored with "gays" in the military ... why not make them our Secret Police as Hitler did?
I truly find this shocking .. what is going on and the dam sheeple have their heads up their you know whats. If this isn't fascism and a Communist take over I don't know what is. What does it take to wake up these freaking morons? pissed as hell. We attend out tea parties for sanity.
Just as in South America.
Are you serious?
"I truly find this shocking .. what is going on and the dam sheeple have their heads up their you know whats. If this isn't fascism and a Communist take over I dont know what is. What does it take to wake up these freaking morons?"
Be patient. There's reaction to obuma and the organization to confront the fascists in Washington is bubbling under the surface.
The states told DC to take their drivers license ID and shove it and now Washington has dropped the idea. The states are discovering their 10th amendment muscles. We need to let this play out.
Frankly, I'm impressed by conservative Americans who are playing by the rule of law and seeing if it still works, despite the fact that the thieves in Washington are breaking dozens of laws each day. This bodes well for the present and the future. That discipline of character and respect for our institutions can and will create an unstoppable force.
The thieving leftist thugs in DC are nothing more than an unruly mob, interested only in money, power and not working.
I found one incident this past winter very revealing and it showed me what we're facing. Remember when obuma called on his supporters to meet and go door-to-door to gather signtaures pledging fealty to king obuma? Well, nobody showed up.
His leftist army was more interested in surfing bikini.com, eating fried chicken and collecting welfare checks. Today's American leftists are cowards - fat, simpering cowards. You could not go to LA, DC and Chicago and raise a a single squad for the Lincoln Brigade. The American leftist now is a self-centered, fat egomaniac. They will not slip on a pack, grab a rifle and charge a perimeter for the glory of obuma.
The obuma thugs have overestimated their power over their followers. For all the indoctrination, for all the propaganda, for all the lies, the leaders of the American left haven't created a disciplined leftist army. Instead, they've molded a gang of lazy and fat welfare slobs.
These Marxists in Washington are still living in the early 20th century, thinking they can lead a Bolshevik Army to march across America and create a worker's paradise. They're trying to duplicate Lenin's revolution. What worked in Russia in 1917 won't work in America in 2009. There wil be no civilian army as big and well-equipped as the military. All obuma has is a bunch of ignorant, fat, stupid leftists shaking the bushes and pretending it's an army. It's classic Sun-Tzu.
They're fools, but dangerous fools. They're stupid, but stupid people do stupid things.
We need to stay active and alert but not allow a bunch of conservative hotheads to roll the guillotine down Pennsylvania Avenue.
If I could draw parallel time lines between today and our first revolutionary war, I'd guess we're at about 1770. We're progressing well and moving much faster than I thought we would.
All these state resolutions, all the tea parties, all the citizens showing up at townhall meetings to confront the fascist, criminal congress, are a loud reaffirmation of our Declaration of Independence. And it will get louder. King obuma is in his death throes.
The Founders left us the documents, the freedom and the spirit to handle an emergency such as this. We will succeed. There will be justice.
I'm very encouraged and hopeful.
I am completely serious.
They did not shoot, and I do not think they —the Secret Service— was shouting, or giving orders.
But they had their rifles leveled at the crowd, as they were driving along in their SUV.
I do not mean they were in possession of weapons —it would be strange if they did not have any, or if they did not have very powerful weapons somewhere, or even on their person physically; that is a very basic tool of protecting POTUS, whomever he is.
Instead, what I mean is that those weapons were loaded, shouldered, and leveled at the crowed, and that they had every appearance of aiming in such a way that suggested that there was a high likelihood of some threat, or some type of violence.
I do not know what their orders were, or what type of information they may have been acting on.
I was hugely shocked to hear about this.
I'm shocked as well.
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News Release: Tallahassee Fire Department
Tallahassee, Fla. -- Each New Year's Eve, thousands of people, most often children and teens, are injured while using consumer fireworks. Despite the dangers of fireworks, few people understand the associated risks - devastating burns, other injuries, fires, and even death. The Tallahassee Fire Department would like to remind you to use extreme caution when using fireworks this New Year's Eve.
More than half the firework related injuries in the U.S. involve children under 15 years old. If you plan to use legal fireworks at home, the Tallahassee Fire Department recommends the following:


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- Report: #1065944
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Complaint Review: ideal leads
ideal leads1481 N.W. North River Drive miami, Florida USA
ideal leads Leads They Sell Are Fake and They Do Not Honor Their Contract miami Florida
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They claim to sell life insurance leads to insurance companies. Over a 1/3 of the numbers were disconnected or wrong numbers. Not one person I spoke to wanted information on life insurance, I did not produce one application. It was a waste of my time. I spent 3 days call people and getting hung up on. this is just bad business. The company won't honor their refund policy and were extremely rude to me and hung up on me and wouldn't return my phone calls
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text: tejon ranch Tejon Ranch Launches Plan For New 'Grapevine' City, With 12,000 Homes By Ezra David Romero • Nov 12, 2013 Ezra David Romero / Valley Public Radio Do you know that moment when you're driving north on Interstate 5 through the Tehachapi Mountains when the wide expanse of the San Joaquin Valley comes into view? On a clear day, it's an impressive sight. But next time you're there - look around. Most of what you see, from the hills down to the valley floor is a part of the Tejon Ranch –the largest privately owned piece of land in California. And it's here – right at the base of the mountains, where Interstate 5 and Highway 99 meet that developers from the ranch are planning a new town – known simply as Grapevine. Christo's Umbrellas still fresh in memory, 20 years later By Joe Moore • Oct 26, 2011 In October 1991, Vikki Cruz was just 11 years old, but the current curator of the Bakersfield Museum of Art remembers one trip up Interstate 5 that year very well.


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...and how with the squad we had how we'd be lucky to finish in the Europa places. And then it all becomes '....but 'arry failed us because he didn't get 3rd....'.Good job, I've got a brain like a gold fish, as I'm quite happy to have the same 'new' conversation over and over. But irrespective of all that, the striker situation is a concern - but there is still another month to get something sorted. A lot can happen in a month as we've seen in the past. I'd like to think that they are also looking at the keeper situation and maybe some wide cover.If you look at who we had in the squad at the start of last season, and think we need replacements for those who have gone:PavCrouchKrancjarKingCorlukaAlnwickIf Caulker stays around, then with Vertonghen then maybe CB is ok even if Gallas goes. RB seems short, but again if Naughton is back. Krancjar/Gylfi seems ok. So with Ade and Saha coming and going we're still left with a 2 striker gap in the squad.


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Sparta took a third minute lead through Johan Voskamp who beat the offside trap before slotting past Tom Heaton.
But the Clarets roared into action with three goals in 19 minutes. Austin's first came in the fifth when he got on the end of Danny Lafferty's cross to plant his header past the Rotterdam goalkeeper.
Austin missed when clean through moments later but he made amends after 22 minutes when he crossed for Dean Marney to slam home from six yards.
Danny Ings got onto the scoresheet two minutes later when he neatly exchanged passes with Austin before coolly slotting home.
And Austin grabbed his second 18 minutes from time after getting on the end of a David Jones shot.
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With the northern highlands enveloped in snow and the cities ablaze with Christmas lights and fireworks, winter makes for an atmospheric time to visit Scotland, as well as being one of the cheapest times to travel.
As the days get shorter, the country's frosted landscapes and high winds make winter sports a popular option and Scotland's five ski centers offer skiing and snowboarding at a fraction of the price of continental Europe. Hiking and mountaineering are popular pastimes in Scotland all year round, but while the icy passes make it a tougher challenge in the colder months, the snow-dusted views are well worth the effort. Windsurfing is also huge in coastal areas, with some of the world's biggest windsurfing competitions held on Scottish shores.
Planning a Trip? Check out Viator's Scotland tours, Scotland attractions, and Scotland travel recommendations.
Winter in Scotland is also a time for festivities, starting with St Andrew's Day on November 30th. This celebration of the patron Saint of Scotland is a public holiday and marked by a range of art shows, storytelling performances, traditional dance festivals and cultural events held around the country. Christmas is next up, with Christmas markets, sparkling decorations and ice skating rinks popping up, especially in Edinburgh and Glasgow. The biggest party of the year though, is New Year – known as Hogmanay in Scotland – a four-day extravaganza with torch-lit processions, bonfires, live music concerts and street parties held all over the country. The biggest event is held in Edinburgh, with over 250,000 descending on the city, but Glasgow's street party, the Inverness Highland Fling and Stonehaven fireball ceremony are also popular options.
Keep some energy reserves for January though – Burns night, held on January 25th, is another reason to party, celebrating the life and times of Scotland's national poet, Robert Burns. Join in the traditional Burns supper and sample the iconic Scottish haggis (traditionally doused with a healthy splash of Scotch whisky), as bagpipes are played in the background.


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The Preparatory School workshop/recital system offers students valuable performance experience and a wide range of viewpoints through direct feedback from various instructors. Students are recommended for workshops by their private teacher. After completion of the workshop, written reports made by another member of the faculty are available to the student. Students performing in workshops will normally play in a departmental recital the following week. Each student should participate in at least one workshop/recital per semester.
Preparatory student recitals are scheduled on Saturdays throughout the year. These are free and open to the public. Students are recommended for recital programs based on their performance in workshops. In addition to group recitals, students are encouraged to perform solo recitals. All performances must be approved by the teacher.
Piano workshops and recitals are from 12:00-1:00 p.m. or from 4:00-5:00 p.m.
If you have any questions/conflicts, please call 617-585-1132.
Piano Workshop/Recital Schedule 2015-2016
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Work experience scheme provides steps to employment
Published by Becki Ord for IPB Communications in Housing and also in Communities
Winston Meredith is now working with Keepmoat on the regeneration of Pendleton Together
A WORK experience scheme to help unemployed Salford residents get a foot on the career ladder has had its first success story and promises many more opportunities for people looking for a job.
The scheme run by Pendleton Together, the £650 million project regenerating Pendleton in Salford, offers jobseekers the chance to gain eight weeks' work experience in a variety of different roles.
The consortium behind the regeneration of Pendleton plans to offer around 2,000 placements over the next 30 years and wants to hear from anyone interested in gaining work experience.
Winston Meredith, 51, is the first person to benefit from the scheme after being referred by Jobcentre Plus, after being laid off from his job as a security guard at the beginning of the year. The father-of-four had experience working in construction, but was struggling to find full-time work.
He spent eight weeks working on site with the scheme's construction partner Keepmoat as a labourer. Fearing he may never work again, Winston was delighted when Keepmoat offered him a full-time role with the company.
Winston said: "I was really worried when I lost my job in February last year. I have a mortgage and feared I would never work again. I was willing to try anything that would help me back into work and thought this experience would stand me in good stead, even if I wasn't offered a job at the end.
"Being out of work really knocks your self-esteem, so it was brilliant to be offered a full time role. I would recommend this scheme to anyone who wants to take a big step forward in getting back to work."
Winston, who started a 12-month contract with regeneration specialist Keepmoat at the end of November, is now hoping to gain more qualifications and wants to become a gas engineer in the future.
He said: "I am over the moon and my kids are so proud of me. This job has given me hope for the future and it is great to be part of a scheme which will see the lives of the people of Pendleton changed forever."
Jean Thompson, Supporting Communities Manager with Pendleton Together, said: "The scheme is offering many places for people wanting to get back into work.
Winston is just the first and a great example of how undertaking work experience can lead to future full-time roles. We have many work experience opportunities and we would urge people to get in touch if they want to find out more. "
Frank Mondino, Keepmoat Area Director, said: "We were delighted to be able to offer Winston a full time job. He is hard working and has already become a valued member of the team.
"Anyone undertaking construction work experience on this project can expect to leave site with the experience they need to find a full-time role."
The project, which aims to breathe new life into the Pendleton area of Salford, will see more than 1,600 new homes built and 1,250 existing homes refurbished. There will also be huge changes across the community including new parks, open spaces and even a community farm.
Work experience opportunities are available in a range of jobs including labouring, joinery, environmental services, administration and civil engineering, and are open to people of all ages.
Assistant Mayor for Employment, and Langworthy Councillor, Paul Dennett said: "I'm delighted for Winston and his family that he has been given this new opportunity. He'll get his self-esteem back, learn new skills and help to build a better future for Pendleton's residents.
"The Creating a New Pendleton scheme is helping to transform the area and now it is changing lives.
"The scheme will make a huge difference to the local area, bringing new housing, new jobs and opportunities, and new business to Pendleton."
In addition to the new homes, the regeneration of Pendleton is set to generate 500 jobs; create 24 new small and medium business enterprises; provide skills training for 3,200 local people and 2,000 work experience opportunities.
The consortium, Pendleton Together, which is delivering the regeneration project, includes social landlord Together Housing Group and building and regeneration specialist Keepmoat. Pendleton Together is working in partnership with Salford City Council.
For more information on the training opportunities available please visit the website http://www.pendletontogether.co.uk/looking-for-a-job/ or call 0300 555 5567.
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A private university of 11,000 students near the center of Dallas, SMU offers strong undergraduate, graduate, and professional programs through seven schools.
SMU's Willis M. Tate Distinguished Lecture Series has announced the upcoming speakers for the 2016-17 season, including astronaut Scott Kelly, PepsiCo CEO Indra Nooyi, actor Alan Alda, historian Doris Kearns Goodwin and journalist Tom Brokaw.
Students grasp abstract math concepts after they demonstrate them with arm motions. Learn more.
Making A DifferenceBrittany Merrill Underwood '07 founded the Akola Project to better the lives of Ugandan women and children.
Jackie Wins BronzeSMU's Jackie Galloway cheered by U.S. and Mexico for winning a bronze medal in taekwondo.
Corral Match-UpThis fall marks the 10th anniversary of when Marielle and Alex met - on a Mustang Corral trip - and later married.
School Closings StudyResearchers find that black and impoverished students suffer greater impact from closure of Houston schools.
The Class of 2020SMU welcomes the Class of 2020. See the photos and videos from their first days at the University.
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Mustang Minute VideosThe SMU community and friends are enjoying the Starbucks coffee shop that recently opened in Fondren Library.
SMU MagazineVisit the SMU Magazine for news and updates of interest to alumni and the community.
Future SMU FacilitiesSMU Athletics reveals future facilities projects, including a new Indoor Performance Center and a new soccer stadium.
To see if SMU is right for you, schedule your visit online today.