Si la définition du « génie » reste floue, les Britanniques ont dressé une liste des cent « génies » vivants, avec quelques surprises… Qu’est-ce qui unit le champion d’échec Garry Kasparov, le terroriste Oussama Ben Laden, l’ex-président Nelson Mandela et le producteur de téléréalité Jon de Mol ? Ils figurent tous, pour le meilleur ou pour le pire, sur la liste des 100 « génies » vivants, établie par le cabinet Synectics. Les mathématiciens règnent sur l’intellect 4.000 Britanniques se sont vu demander par e-mail de désigner librement 10 personnes vivantes qu’ils considéraient comme des « génies ». La liste de 400 noms ainsi compilée a été soumise à un panel d’experts chargés de noter les aspirants génies sur plusieurs critères, la définition d’un « génie » étant difficile à donner.

IDimanche#160;:/I CS Verviers #8211; Cappellen 1-1#160;; CS Vis#233; #8211; RC Malines 2-0#160;; La Calamine #8211; Dessel Sport 1-2#160;; Hamoir #8211; Veldwezelt 1-3#160;; Willebroek #8211; Tongres 3-1#160;; Bocholt #8211; Boom 1-2. ISamedi#160;:/I Turnhout #8211; Seraing 3-0#160;; Mol-Wezel #8211; Hoogstraten 0-3. IClassement#160;:/I (13#160;m. sauf indication contraire) 1. Vis#233; 26pts ; 2.Hoogstraten (14m.) 26#160;; 3.Turnhout (12m.) 25#160;; 4.Willebroek 25#160;; 5.Tongres 24#160;; 6. RC Malines 22#160;; 7.Boom (12m.) 20#160;; 8.Veldwezelt 19#160;; 9.Bocholt 18#160;; 10.Dessel Sport 16#160;; 11.CS Verviers 15#160;; 12.Mol-Wezel 14#160;; 13.Seraing 12#160;; 14.Hamoir 9#160;; 15.Cappellen (12m.) 7#160;; 16.La Calamine 4#160;.img width='1' height='1' src='http://rss.feedsportal.com/c/864/f/11087/s/27887a2/mf.gif' border='0'/br/br/a href="http://da.feedsportal.com/r/24193151313/u/89/f/11087/c/864/s/41453474/a2.htm"img src="http://da.feedsportal.com/r/24193151313/u/89/f/11087/c/864/s/41453474/a2.img" border="0"//a

IDimanche#160;:/I CS Verviers #8211; Cappellen 1-1#160;; CS Vis#233; #8211; RC Malines 2-0#160;; La Calamine #8211; Dessel Sport 1-2#160;; Hamoir #8211; Veldwezelt 1-3#160;; Willebroek #8211; Tongres 3-1#160;; Bocholt #8211; Boom 1-2. ISamedi#160;:/I Turnhout #8211; Seraing 3-0#160;; Mol-Wezel #8211; Hoogstraten 0-3. IClassement#160;:/I (13#160;m. sauf indication contraire) 1. Vis#233; 26pts ; 2.Hoogstraten (14m.) 26#160;; 3.Turnhout (12m.) 25#160;; 4.Willebroek 25#160;; 5.Tongres 24#160;; 6. RC Malines 22#160;; 7.Boom (12m.) 20#160;; 8.Veldwezelt 19#160;; 9.Bocholt 18#160;; 10.Dessel Sport 16#160;; 11.CS Verviers 15#160;; 12.Mol-Wezel 14#160;; 13.Seraing 12#160;; 14.Hamoir 9#160;; 15.Cappellen (12m.) 7#160;; 16.La Calamine 4#160;.img width='1' height='1' src='http://rss.feedsportal.com/c/864/f/11087/s/27887a2/mf.gif' border='0'/br/br/a href="http://da.feedsportal.com/r/24193151313/u/89/f/11087/c/864/s/41453474/a2.htm"img src="http://da.feedsportal.com/r/24193151313/u/89/f/11087/c/864/s/41453474/a2.img" border="0"//a

Publication Date: 2008 Nov 14 PMID: 19038270br/Authors: Batta, K. - Yokokawa, M. - Takeyasu, K. - Kundu, T. K.br/Journal: J Mol Biolbr/br/Human transcriptional coactivator PC4 is a highly abundant nuclear protein that is involved in diverse cellular processes ranging from transcription to chromatin organization. Earlier, we have shown that PC4, a positive activator of p53, overexpresses upon genotoxic insult in a p53-dependent manner. In the present study, we show that PC4 stimulates ligase-mediated DNA end joining irrespective of the source of DNA ligase. Pull-down assays reveal that PC4 helps in the association of DNA ends through its C-terminal domain. In vitro nonhomologous end-joining assays with cell-free extracts show that PC4 enhances the joining of noncomplementary DNA ends. Interestingly, we found that PC4 activates double-strand break (DSB) repair activity through stimulation of DSB rejoining in vivo. Together, these findings demonstrate PC4 as an activator of nonhomologous end joining and DSB repair activity.br/br/post to: a href = http://www.citeulike.org/posturl?url=http%3A%2F%2Fwww.ncbi.nlm.nih.gov%2Fentrez%2Fquery.fcgi%3Fcmd%3DRetrieve%26db%3DPubMed%26dopt%3DAbstract%26list_uids%3D19038270title=Entrez+PubmedCiteULike/a

Publication Date: 2008 Nov 12 PMID: 19038269br/Authors: Zhao, L. - Pellenz, S. - Stoddard, B. L.br/Journal: J Mol Biolbr/br/The restriction endonuclease fold [a three-layer alpha-beta sandwich containing variations of the PD-(D/E)XK nuclease motif] has been greatly diversified during evolution, facilitating its use for many biological functions. Here we characterize DNA binding and cleavage by the PD-(D/E)XK homing endonuclease I-Ssp6803I. Unlike most restriction endonucleases harboring the same core fold, the specificity profile of this enzyme extends over a long (17 bp) target site. The DNA binding and cleavage specificity profiles of this enzyme were independently determined and found to be highly correlated. However, the DNA target sequence contains several positions where binding and cleavage activities are not tightly coupled: individual DNA base-pair substitutions at those positions that significantly decrease cleavage activity have minor effects on binding affinity. These changes in the DNA target sequence appear to correspond to substitutions that uniquely increase the free energy from the ground state and transition state, rather than simply decreasing the overall DNA binding affinity. The specificity of the enzyme reflects constraints on its host gene and limitations imposed by the enzyme's quaternary structure and illustrate the highly diverse repertoire of DNA recognition specificities that can be adopted by the related folds surrounding the PD-(D/E)XK nuclease motif.br/br/post to: a href = http://www.citeulike.org/posturl?url=http%3A%2F%2Fwww.ncbi.nlm.nih.gov%2Fentrez%2Fquery.fcgi%3Fcmd%3DRetrieve%26db%3DPubMed%26dopt%3DAbstract%26list_uids%3D19038269title=Entrez+PubmedCiteULike/a

Publication Date: 2008 Nov 12 PMID: 19038268br/Authors: Silverman, A. P. - Levin, A. M. - Lahti, J. L. - Cochran, J. R.br/Journal: J Mol Biolbr/br/The alpha(v)beta(3) integrin receptor is an important cancer target due to its overexpression on many solid tumors and the tumor neovasculature and its role in metastasis and angiogenesis. We used a truncated form of the Agouti-related protein (AgRP), a 4-kDa cystine-knot peptide with four disulfide bonds and four solvent-exposed loops, as a scaffold for engineering peptides that bound to alpha(v)beta(3) integrins with high affinity and specificity. A yeast-displayed cystine-knot peptide library was generated by substituting a six-amino-acid loop of AgRP with a nine-amino-acid loop containing the Arg-Gly-Asp integrin recognition motif and randomized flanking residues. Mutant cystine-knot peptides were screened in a high-throughput manner by fluorescence-activated cell sorting to identify clones with high affinity to detergent-solubilized alpha(v)beta(3) integrin receptor. Select integrin-binding peptides were expressed recombinantly in Pichia pastoris and were tested for their ability to bind to human cancer cells expressing various integrin receptors. These studies showed that the engineered AgRP peptides bound to cells expressing alpha(v)beta(3) integrins with affinities ranging from 15 nM to 780 pM. Furthermore, the engineered peptides were shown to bind specifically to alpha(v)beta(3) integrins and had only minimal or no binding to alpha(v)beta(5), alpha(5)beta(1), and alpha(iib)beta(3) integrins. The engineered AgRP peptides were also shown to inhibit cell adhesion to the extracellular matrix protein vitronectin, which is a naturally occurring ligand for alpha(v)beta(3) and other integrins. Next, to evaluate whether the other three loops of AgRP could modulate integrin specificity, we made second-generation libraries by individually randomizing these loops in one of the high-affinity integrin-binding variants. Screening of these loop-randomized libraries against alpha(v)beta(3) integrins resulted in peptides that retained high affinities for alpha(v)beta(3) and had increased specificities for alpha(v)beta(3) over alpha(iib)beta(3) integrins. Collectively, these data validate AgRP as a scaffold for protein engineering and demonstrate that modification of a single loop can lead to AgRP-based peptides with antibody-like affinities for their target.br/br/post to: a href = http://www.citeulike.org/posturl?url=http%3A%2F%2Fwww.ncbi.nlm.nih.gov%2Fentrez%2Fquery.fcgi%3Fcmd%3DRetrieve%26db%3DPubMed%26dopt%3DAbstract%26list_uids%3D19038268title=Entrez+PubmedCiteULike/a

Publication Date: 2008 Nov 14 PMID: 19038267br/Authors: Biancalana, M. - Makabe, K. - Koide, A. - Koide, S.br/Journal: J Mol Biolbr/br/A number of small organic molecules have been developed that bind to amyloid fibrils, a subset of which also inhibit fibrillization. Among these, the benzothiol dye Thioflavin-T (ThT) has been used for decades in the diagnosis of protein-misfolding diseases, and in kinetic studies of self-assembly (fibrillization). Despite its importance, efforts to characterize the ThT binding mechanism at the atomic level have been hampered by the inherent insolubility and heterogeneity of peptide self-assemblies. To overcome these challenges, we have developed a minimalist approach to designing a ThT-binding site in a peptide self-assembly mimic (PSAM) scaffold. PSAMs are engineered water-soluble proteins that mimic a segment of beta-rich peptide self-assembly, and they are amenable to standard biophysical techniques and systematic mutagenesis. The PSAM beta-sheet contains rows of repetitive amino acid patterns running perpendicular to the strands (cross-strand ladders) that represent a ubiquitous structural feature of fibril-like surfaces. We successfully designed a ThT binding site that recapitulates the hallmarks of ThT-fibril interactions by constructing a cross-strand ladder consisting of contiguous tyrosines. The X-ray crystal structures suggest that ThT interacts with the beta-sheet by docking onto surfaces formed by a single tyrosine ladder, rather than in the space between adjacent ladders. Systematic mutagenesis further demonstrated that tyrosine surfaces across four or more beta-strands formed the minimal binding site for ThT. Our work thus provides structural insights into how this widely used dye recognizes a prominent subset of peptide self-assemblies, and proposes a strategy to elucidate the mechanisms of fibril-ligand interactions.br/br/post to: a href = http://www.citeulike.org/posturl?url=http%3A%2F%2Fwww.ncbi.nlm.nih.gov%2Fentrez%2Fquery.fcgi%3Fcmd%3DRetrieve%26db%3DPubMed%26dopt%3DAbstract%26list_uids%3D19038267title=Entrez+PubmedCiteULike/a

Publication Date: 2008 Nov 14 PMID: 19038266br/Authors: Meinhardt, J. - Sachse, C. - Hortschansky, P. - Grigorieff, N. - Fandrich, M.br/Journal: J Mol Biolbr/br/Amyloid fibrils characterize a diverse group of human diseases that includes Alzheimer's disease, Creutzfeldt-Jakob and type II diabetes. Alzheimer's amyloid fibrils consist of amyloid-beta (Abeta) peptide and occur in a range of structurally different fibril morphologies. The structural characteristics of 12 single Abeta(1-40) amyloid fibrils, all formed under the same solution conditions, were determined by electron cryo-microscopy and three-dimensional reconstruction. The majority of analyzed fibrils form a range of morphologies that show almost continuously altering structural properties. The observed fibril polymorphism implies that amyloid formation can lead, for the same polypeptide sequence, to many different patterns of inter-or intra-residue interactions. This property differs significantly from native, monomeric protein folding reactions that produce, for one protein sequence, only one ordered conformation and only one set of inter-residue interactions.br/br/post to: a href = http://www.citeulike.org/posturl?url=http%3A%2F%2Fwww.ncbi.nlm.nih.gov%2Fentrez%2Fquery.fcgi%3Fcmd%3DRetrieve%26db%3DPubMed%26dopt%3DAbstract%26list_uids%3D19038266title=Entrez+PubmedCiteULike/a

Publication Date: 2008 Nov 14 PMID: 19038265br/Authors: Torrance, G. M. - Leader, D. P. - Gilbert, D. R. - Milner-White, E. J.br/Journal: J Mol Biolbr/br/We have surveyed the bridging of pairs of main chain carbonyl oxygens by cations or by delta(+) hydrogens within hydrogen bonding groups. A three to four residue motif, which we call the niche, with characteristic varphi,psi angles, is by far the commonest feature with this property. The niche accommodates atoms or groups that offer delta+ charges, including water molecules or metal ions, as well as amines, guanidines, and other NH(2) groups. Seven percent of all residues in an average soluble protein belong to a niche; another 7% have the niche conformation but no obvious bridging delta+ group. Fifty-five percent of niches occur either following a type 1 beta-turn or at the C-termini of alpha-helices, and niches turn out to be the most common C-terminal features of alpha-helices: 39% of alpha-helical C-termini are niches, whereas 34% are Schellman loops. 3(10) helices also frequently terminate in niches. Niches that bind K(+), Na(+) or Ca(2+) occur in some functional contexts: in the cyclic peptides valinomycin and antamanide; and in several enzymes that are allosterically activated by Na(+) or K(+) In the calcium pump, a niche is integrally involved in the ion transport.br/br/post to: a href = http://www.citeulike.org/posturl?url=http%3A%2F%2Fwww.ncbi.nlm.nih.gov%2Fentrez%2Fquery.fcgi%3Fcmd%3DRetrieve%26db%3DPubMed%26dopt%3DAbstract%26list_uids%3D19038265title=Entrez+PubmedCiteULike/a

Publication Date: 2008 Nov 8 PMID: 19038264br/Authors: Cutler, T. A. - Mills, B. M. - Lubin, D. J. - Chong, L. T. - Loh, S. N.br/Journal: J Mol Biolbr/br/Fusion of one protein domain with another is a common event in both evolution and protein engineering experiments. When insertion is at an internal site (e.g., a surface loop or turn), as opposed to one of the termini, conformational strain can be introduced into both domains. Strain is manifested by an antagonistic folding-unfolding equilibrium between the two domains, which we previously showed can be parameterized by a coupling free-energy term (DeltaG(X)). The extent of strain is predicted to depend primarily on the ratio of the N-to-C distance of the guest protein to the distance between ends of the surface loop in the host protein. Here, we test that hypothesis by inserting ubiquitin (Ub) into the bacterial ribonuclease barnase (Bn), using peptide linkers from zero to 10 amino acids each. DeltaG(X) values are determined by measuring the extent to which Co(2+) binding to an engineered site on the Ub domain destabilizes the Bn domain. All-atom, unforced Langevin dynamics simulations are employed to gain structural insight into the mechanism of mechanically induced unfolding. Experimental and computational results find that the two domains are structurally and energetically uncoupled when linkers are long and that DeltaG(X) increases with decreasing linker length. When the linkers are fewer than two amino acids, strain is so great that one domain unfolds the other. However, the protein is able to refold as dimers and higher-order oligomers. The likely mechanism is a three-dimensional domain swap of the Bn domain, which relieves conformational strain. The simulations suggest that an effective route to mechanical unfolding begins with disruption of the hydrophobic core of Bn near the Ub insertion site.br/br/post to: a href = http://www.citeulike.org/posturl?url=http%3A%2F%2Fwww.ncbi.nlm.nih.gov%2Fentrez%2Fquery.fcgi%3Fcmd%3DRetrieve%26db%3DPubMed%26dopt%3DAbstract%26list_uids%3D19038264title=Entrez+PubmedCiteULike/a