pFor all the magnificent diversity of life on this planet, ranging from tiny bacteria to majestic blue whales, from sunshine-harvshy;shy;estshy;shy;ing plants to mineral-digesting endoliths miles underground, only one kind of ldquo;life as we know itrdquo; exists. All these organisms are based on nucleic acids--DNA and RNA--and proteins, working together more or less as described by the so-called central dogma of molecular biology: DNA stores information that is transcribed into RNA, which then serves as a template for producing a protein. The proteins, in turn, serve as important structural elements in tissues and, as enzymes, are the cellrsquo;s workhorses./ppYet scientists dream of synthesizing life that is utterly alien to this world--both to better understand the minimum components required for life (as part of the quest to uncover the essence of life and how life originated on earth) and, frankly, to see if they can do it. That is, they hope to put together a novel combination of molecules that can self-organize, metabolize (make use of an energy source), grow, reproduce and evolve./p a href=http://www.sciam.com/article.cfm?id=triple-helix-designing-a-new-molecule[More]/a

iAdvances in experimental medicine and biology, Vol. 630 (2008), pp. 189-205./ibr /br /Loss of normal growth control is a hallmark of cancer. Thus, understanding the mechanisms of tissue-specific, normal growth regulation and the changes that occur during tumorigenesis may provide insights of both diagnostic and therapeutic importance. Control of cell proliferation in the normal mammary gland is steroid hormone (estrogen and progestin)-dependent, involves complex interactions with other hormones, growth factors and cytokines and ultimately converges on activation of three proto-oncogenes (c-Myc, cyclin D1 and cyclin E1) that are rate limiting for the G1 to S phase transition during normal cell cycle progression. Mammary epithelial cell-specific overexpression of these genes induces mammary carcinoma in mice, while cyclin D1 null mice have arrested mammary gland development and are resistant to carcinoma induced by the neu/erbB2 and ras oncogenes. Furthermore, c-Myc, cyclins D1, E1 and E2 are commonly overexpressed in primary breast cancer where elevated expression is often associated with a more aggressive disease phenotype and an adverse patient outcome. This may be due in part to overexpression of these genes conferring resistance to endocrine therapies since in vitro studies provide compelling evidence that overexpression of c-Myc and to a lesser extent cyclin D1 and cyclin E1, attenuate the growth inhibitory effects of SERMS, antiestrogens and progestins in breast cancer cells. Thus, abnormal regulation of the expression of cell cycle molecules, involved in the steroidal control of cell proliferation in the mammary gland, are likely to be directly involved in the development, progression and therapeutic responsiveness of breast cancer. Furthermore, a more detailed understanding of these pathways may identify new targets for therapeutic intervention particularly in endocrine-unresponsive and endocrine-resistant disease.br /iAJ Butt, CE Caldon, CM McNeil, A Swarbrick, EA Musgrove, RL Sutherland/i

iEndocrine-related cancer, Vol. 10, No. 2. (June 2003), pp. 179-186./ibr /br /The central involvement of estrogen in the development of the mammary gland and in the genesis of breast cancer has lent impetus to studies of the links between estrogen action and the cell cycle machinery. Recent studies of the estrogenic regulation of molecules with known roles in the control of G1/S phase progression have resulted in significant advances in understanding these links. Estrogens independently regulate the expression and function of c-Myc and cyclin D1 and the induction of either c-Myc or cyclin D1 is sufficient to recapitulate the effects of estrogen on cell cycle progression. These pathways converge at the activation of cyclin E-Cdk2 complexes. The active cyclin E-Cdk2 complexes are depleted of the cyclin dependent kinase (CDK) inhibitor p21(WAF1/CIP1) because of estrogen-mediated inhibition of nascent p21(WAF1/CIP1). Insulin and estrogen synergistically stimulate cell cycle progression, and the ability of estrogen to antagonize an insulin-induced increase in p21(WAF1/CIP1) gene expression appears to underlie this effect. Antiestrogen treatment of MCF-7 cells leads to an acute decrease of c-Myc expression, a subsequent decline in cyclin D1, and ultimately arrest of cells in a state with features characteristic of quiescence. An antisense-mediated decrease in c-Myc expression results in decreased cyclin D1 expression and inhibition of DNA synthesis, mimicking the effects of antiestrogen treatment and emphasizing the importance of c-Myc as an estrogen/antiestrogen target. These data identify c-Myc, cyclin D1, p21(WAF1/CIP1) and cyclin E-Cdk2 as central components of estrogen regulation of cell cycle progression and hence as potential downstream targets that contribute to the role of estrogen in oncogenesis.br /iSF Doisneau-Sixou, CM Sergio, JS Carroll, R Hui, EA Musgrove, RL Sutherland/i

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: 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 28 PMID: 19039131br/Authors: Rupar, P. A. - Staroverov, V. N. - Baines, K. M.br/Journal: Sciencebr/br/Unlike cations of metals such as sodium or calcium, oxidized silicon and germanium centers generally require strongly bound covalent ligands. We report the synthesis and characterization of a germanium(II) dication in the form of the salt (Ge.cryptand[2.2.2])(O3SCF3)2. The salt is isolated in 88% yield from the reaction of cryptand [2.2.2] and an N-heterocyclic carbene complex of GeCl(O3SCF3) as an air-sensitive, white solid. The crystal structure of the salt shows minimal interaction between the cryptand-encapsulated germanium(II) ion and the two -O3SCF3 counterions. These results suggest a widely expanded role of cryptands and related molecules in stabilizing nonmetallic cations.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%3D19039131title=Entrez+PubmedCiteULike/a

Not sure how this one slipped past us, but last month Science magazine challenged its readers to translate their PhD research into an interpretive dance and post their moves on YouTube. Thirty-six videos were submitted and last week the winners were chosen.

It’s not exactly “news” at this point (hat tip to Slashdot for pointing it out), but if you’ve ever wondered what “Resolving Pathways of Functional Coupling in Human Hemoglobin Using Quantitative Low Temperature Isoelectric Focusing of Asymmetric Mutant Hybrids.” would look like as a dance — you’re in luck. Vince LiCata, a biochemist at Louisiana State University, Baton Rouge won in the professors category for this performance.

The winner in the graduate student category was Sue Lynn Lau from Australia, who won for this interpretation of “The role of vitamin D in beta-cell function.”

The postdoc winner was Miriam Sach, whose solo dance took top prize for illustrating “Cerebral activation patterns induced by inflection of regular and irregular verbs with positron emission tomography: A comparison between single subject and group analysis.”

And the popular choice winner (which was determined by who got the most views) was PhD candidate Markita Landry who did this physics tango to “Single Molecule Measurements of Protelomerase TelK-DNA Complexes.”

Winners will be paired with professional choreographers to turn their paper into a dance that will be part of a single, four-part performance built around the research.

img src="http://c.fsdn.com/fm/screenshots/58939_thumb.png" align="right" alt="Screenshot" hspace="10" vspace="10" The Gnome Chemistry Utils includes the following programs: a 2D chemical editor (GChemPaint), a chemical calculator (computes raw formule, molar weight, mass composition, and isotopic pattern), a 3D molecule viewer using OpenGL to display molecular models, a crystal structure viewer and editor, a spectrum viewer, and a periodic table of the elements. hr / strongLicense:/strong GNU General Public License v2 hr / strongChanges:/strongbr / Major bugs were fixed. An issue in GChemPaint with double bond drawing was fixed along with crashes when adding a bond between two molecules and when adding a fourth bond to phosphorus. Various issues related to group symbols were fixed, and all users of GChemPaint are encouraged to upgrade. URIs are now un-escaped before display in all applications. pa href="http://feedads.googleadservices.com/~a/3U0jW4FKUAHVqEl1SlIuBzl29t8/a"img src="http://feedads.googleadservices.com/~a/3U0jW4FKUAHVqEl1SlIuBzl29t8/i" border="0" ismap="true"/img/a/pimg src="http://feedproxy.google.com/~r/freshmeat/feeds/fm-releases-global/~4/36cyMVhZRx0" height="1" width="1"/

img src="http://c.fsdn.com/fm/screenshots/58939_thumb.png" align="right" alt="Screenshot" hspace="10" vspace="10" The Gnome Chemistry Utils includes the following programs: a 2D chemical editor (GChemPaint), a chemical calculator (computes raw formule, molar weight, mass composition, and isotopic pattern), a 3D molecule viewer using OpenGL to display molecular models, a crystal structure viewer and editor, a spectrum viewer, and a periodic table of the elements. hr / strongLicense:/strong GNU General Public License v2 hr / strongChanges:/strongbr / Major bugs were fixed. An issue in GChemPaint with double bond drawing was fixed along with crashes when adding a bond between two molecules and when adding a fourth bond to phosphorus. Various issues related to group symbols were fixed, and all users of GChemPaint are encouraged to upgrade. URIs are now un-escaped before display in all applications. pa href="http://feedads.googleadservices.com/~a/LvN4Zcg2ZfXBaxGkj_YGi1YERG4/a"img src="http://feedads.googleadservices.com/~a/LvN4Zcg2ZfXBaxGkj_YGi1YERG4/i" border="0" ismap="true"/img/a/pimg src="http://feedproxy.google.com/~r/freshmeat/feeds/fm-releases-unix/~4/36cyMVhZRx0" height="1" width="1"/