Hot off the presses! Oct 01 Nature biotechnology

The Oct 01 issue of the Nature biotechnology is now up on Pubget (About Nature biotechnology): if you're at a subscribing institution, just click the link in the latest link at the home page. (Note you'll only be able to get all the PDFs in the issue if your institution subscribes to Pubget.)

Latest Articles Include:

• The twain shall meet
  - Nature Biotechnology 27(10):869 (2009)
  Announcing an initiative to connect commercially oriented academics with their local business community.
• Expanded access rules pose quandary for drug developers
  Mack GS - Nature Biotechnology 27(10):871-872 (2009)
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• FDA penalizes trial misconduct
  Shaffer C - Nature Biotechnology 27(10):872 (2009)
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• Test tube meat on the menu?
  Fox JL - Nature Biotechnology 27(10):873 (2009)
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• Europe plans for drug-making plants
  Wolfson W - Nature Biotechnology 27(10):874 (2009)
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• Pfizer lured to Sweden
  Aldridge S - Nature Biotechnology 27(10):874 (2009)
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• Spotlight focuses on protein-misfolding therapies
  Ratner M - Nature Biotechnology 27(10):874 (2009)
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• Regulation of consumer genomic tests remains in limbo
  Allison M - Nature Biotechnology 27(10):875-877 (2009)
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• Golden Triangle taps Boston
  Aldridge S - Nature Biotechnology 27(10):877 (2009)
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• Fits and starts for Geron
  Defrancesco L - Nature Biotechnology 27(10):877 (2009)
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• Firms seek new models to access public equity
  Mitchell P - Nature Biotechnology 27(10):878-879 (2009)
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• Sanofi's Shantha boost
  Jayaraman K - Nature Biotechnology 27(10):879 (2009)
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• Gulf beckons biotech
  Birch H - Nature Biotechnology 27(10):879 (2009)
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• Under wraps
  Waltz E - Nature Biotechnology 27(10):880-882 (2009)
  Are the crop industry's strong-arm tactics and close-fisted attitude to sharing seeds holding back independent research and undermining public acceptance of transgenic crops? Emily Waltz investigates.
• Credibility: your most important asset
  - Nature Biotechnology 27(10):883-885 (2009)
  
• Is it virtuous to be virtual? The VC viewpoint
  Chakma J Calcagno JL Behbahani A Mojtahedian S - Nature Biotechnology 27(10):886-888 (2009)
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• The power of social networking in medicine
  Brownstein CA Brownstein JS Williams DS Wicks P Heywood JA - Nature Biotechnology 27(10):888-890 (2009)
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• Creating a mouse academic research commons
  Einhorn D Heimes R - Nature Biotechnology 27(10):890-891 (2009)
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• Cofactor-mediated protein promiscuity
  Dimitrov JD Vassilev TL - Nature Biotechnology 27(10):892 (2009)
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• Healthcare-biotech symbiosis
  Ahmed K Ashrafian H - Nature Biotechnology 27(10):892-893 (2009)
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• Improved genome annotation for Zymomonas mobilis
  Yang S Pappas KM Hauser LJ Land ML Chen GL Hurst GB Pan C Kouvelis VN Typas MA Pelletier DA Klingeman DM Chang YJ Samatova NF Brown SD - Nature Biotechnology 27(10):893-894 (2009)
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• Can web 2.0 reboot clinical trials?
  Allison M - Nature Biotechnology 27(10):895-902 (2009)
  Dozens of companies are trying to leverage social networking and other software tools to accelerate trials and reduce their cost.
• Legal uncertainty in the area of genetic diagnostic testing
  Huys I Berthels N Matthijs G Van Overwalle G - Nature Biotechnology 27(10):903-909 (2009)
  A patent landscape analysis of 22 common genetic diagnostic tests shows substantially fewer claims on genes per se than initially suggested but raises questions of legal uncertainty as to the claims' scope.
• Recent patent applications in RNA interference
  - Nature Biotechnology 27(10):910 (2009)
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• siRNA delivery not Toll-free
  Gantier MP Williams BR - Nature Biotechnology 27(10):911-912 (2009)
  Activating the tumor-associated immune system with an siRNA conjugated to a Toll-like receptor 9 ligand is a promising anticancer strategy.
• Snapshots of kinase activities
  Muñoz J Heck AJ - Nature Biotechnology 27(10):912-913 (2009)
  A mass spectrometry–based strategy facilitates sensitive and rapid detection of kinase activities in small amounts of cell lysate.
• Stem cell biology meets p53
  Puzio-Kuter AM Levine AJ - Nature Biotechnology 27(10):914-915 (2009)
  Often called "the guardian of the genome," p53 may also be the guardian of stable development.
• Cancer's insatiable appetite
  Locasale JW Cantley LC Heiden MG - Nature Biotechnology 27(10):916-917 (2009)
  Seemingly unrelated mutations that drive cancer share the ability to promote nutrient uptake and metabolism conducive to cell growth.
• Introducing the acetylome
  Smith KT Workman JL - Nature Biotechnology 27(10):917-919 (2009)
  Mass spectrometry reveals protein acetylation to be as widespread as phosphorylation.
• Research highlights
  Aschheim K Elsner M Hare P Mak C - Nature Biotechnology 27(10):920 (2009)
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• How to visually interpret biological data using networks
  Merico D Gfeller D Bader GD - Nature Biotechnology 27(10):921-924 (2009)
  Networks in biology can appear complex and difficult to decipher. We illustrate how to interpret biological networks with the help of frequently used visualization and analysis patterns.
• In vivo delivery of siRNA to immune cells by conjugation to a TLR9 agonist enhances antitumor immune responses
  Kortylewski M Swiderski P Herrmann A Wang L Kowolik C Kujawski M Lee H Scuto A Liu Y Yang C Deng J Soifer HS Raubitschek A Forman S Rossi JJ Pardoll DM Jove R Yu H - Nature Biotechnology 27(10):925-932 (2009)
  Efficient delivery of small interfering (si)RNA to specific cell populations in vivo remains a formidable challenge to its successful therapeutic application. We show that siRNA synthetically linked to a CpG oligonucleotide agonist of toll-like receptor (TLR)9 targets and silences genes in TLR9+ myeloid cells and B cells, both of which are key components of the tumor microenvironment. When a CpG-conjugated siRNA that targets the immune suppressor gene Stat3 is injected in mice either locally at the tumor site or intravenously, it enters tumor-associated dendritic cells, macrophages and B cells. Silencing of Stat3 leads to activation of tumor-associated immune cells and ultimately to potent antitumor immune responses. Our findings demonstrate the potential of TLR agonist–siRNA conjugates for targeted gene silencing coupled with TLR stimulation and immune activation in the tumor microenvironment.
• Sensitive multiplexed analysis of kinase activities and activity-based kinase identification
  Kubota K Anjum R Yu Y Kunz RC Andersen JN Kraus M Keilhack H Nagashima K Krauss S Paweletz C Hendrickson RC Feldman AS Wu CL Rush J Villén J Gygi SP - Nature Biotechnology 27(10):933-940 (2009)
  Constitutive activation of one or more kinase signaling pathways is a hallmark of many cancers. Here we extend the previously described mass spectrometry–based KAYAK approach by monitoring kinase activities from multiple signaling pathways simultaneously. This improved single-reaction strategy, which quantifies the phosphorylation of 90 synthetic peptides in a single mass spectrometry run, is compatible with nanogram to microgram amounts of cell lysate. Furthermore, the approach enhances kinase monospecificity through substrate competition effects, faithfully reporting the signatures of many signaling pathways after mitogen stimulation or of basal pathway activation differences across a panel of well-studied cancer cell lines. Hierarchical clustering of activities from related experiments groups peptides phosphorylated by similar kinases together and, when combined with pathway alteration using pharmacological inhibitors, distinguishes underlying differences in poten! cy, off-target effects and genetic backgrounds. Finally, we introduce a strategy to identify the kinase, and even associated protein complex members, responsible for phosphorylation events of interest.
• A proteomics approach to discovering natural products and their biosynthetic pathways
  Bumpus SB Evans BS Thomas PM Ntai I Kelleher NL - Nature Biotechnology 27(10):951-956 (2009)
  Many natural products with antibiotic, anticancer and antifungal properties are synthesized by nonribosomal peptide synthetases (NRPSs) and polyketide synthases (PKSs)1. Although genome sequencing has revealed the diversity of these enzymes, identifying new products and their biosynthetic pathways remains challenging2. By taking advantage of the size of these enzymes (often >2,000 amino acids) and unique marker ions derived from their common phosphopantetheinyl cofactor, we adapted mass spectrometry–based proteomics to selectively detect NRPS and PKS gene clusters in microbial proteomes without requiring genome sequence information. We detected known NRPS systems in members of the genera Bacillus and Streptomyces, and screened 22 environmental isolates to uncover production of unknown natural products from the hybrid NRPS-PKS zwittermicin A biosynthetic gene cluster3. We also discovered an NRPS cluster that generates a seven-residue lipopeptide. This 'protein-first' ! strategy complements bioassay- and sequence-based approaches by finding expressed gene clusters that produce new natural products.
• Automated design of synthetic ribosome binding sites to control protein expression
  Salis HM Mirsky EA Voigt CA - Nature Biotechnology 27(10):946-950 (2009)
  Microbial engineering often requires fine control over protein expression—for example, to connect genetic circuits1, 2, 3, 4, 5, 6, 7 or control flux through a metabolic pathway8, 9, 10, 11, 12, 13. To circumvent the need for trial and error optimization, we developed a predictive method for designing synthetic ribosome binding sites, enabling a rational control over the protein expression level. Experimental validation of >100 predictions in Escherichia coli showed that the method is accurate to within a factor of 2.3 over a range of 100,000-fold. The design method also correctly predicted that reusing identical ribosome binding site sequences in different genetic contexts can result in different protein expression levels. We demonstrate the method's utility by rationally optimizing protein expression to connect a genetic sensor to a synthetic circuit. The proposed forward engineering approach should accelerate the construction and systematic optimization of large g! enetic systems.
• Induction of protein-protein interactions in live cells using light
  Yazawa M Sadaghiani AM Hsueh B Dolmetsch RE - Nature Biotechnology 27(10):941-945 (2009)
  Protein-protein interactions are essential for many cellular processes. We have developed a technology called light-activated dimerization (LAD) to artificially induce protein hetero- and homodimerization in live cells using light. Using the FKF1 and GIGANTEA (GI) proteins of Arabidopsis thaliana, we have generated protein tags whose interaction is controlled by blue light. We demonstrated the utility of this system with LAD constructs that can recruit the small G-protein Rac1 to the plasma membrane and induce the local formation of lamellipodia in response to focal illumination. We also generated a light-activated transcription factor by fusing domains of GI and FKF1 to the DNA binding domain of Gal4 and the transactivation domain of VP16, respectively, showing that this technology is easily adapted to other systems. These studies set the stage for the development of light-regulated signaling molecules for controlling receptor activation, synapse formation and other s! ignaling events in organisms.
• Erratum: Sanofi Aventis grooms its ranks for biotech partnering
  Moran N - Nature Biotechnology 27(10):957 (2009)
  Introduction Nat. Biotechnol. 27, 581–582 (2009); published online 8 July 2009; corrected after print 8 October 2009 In the version of this article initially published, the writer incorrectly states that "BiPar was spun out of Genentech to develop small-molecule inhibitors...." The text should have read "BiPar was set up to develop small-molecule inhibitors...." The error has been corrected in the HTML and PDF versions of the article.
• Erratum: Diagnostics firms face new patent claim worries
  Allison M - Nature Biotechnology 27(10):957 (2009)
  Introduction Nat. Biotechnol. 27, 586–587 (2009); published online 8 July 2009; corrected after print 8 October 2009 In the version of this article initially published, on page 587, left column, last paragraph, it states incorrectly that GeneDX holds a patent to certain mutations in the connexin 26 gene related to keratitis-ichthyosis-deafness syndrome. GeneDX does not own that patent. The error has been corrected in the HTML and PDF versions of the article.
• Erratum: Novo awaits green light for diabetes drug
  May M - Nature Biotechnology 27(10):957 (2009)
  Introduction Nat. Biotechnol. 27, 682–685 (2009); published online 7 August 2009; corrected after print 8 October 2009 In the version of this article initially published, GLP-1 was incorrectly described as "glucose-lowering peptide-1"; the correct definition is "glucagon-like peptide-1." The article also stated incorrectly that Amylin and Lilly "filed a new drug application for this drug in July..." referring to Exenatide Once Weekly. This should be corrected to "their new drug application was accepted for review by the FDA in July...." The error has been corrected in the HTML and PDF versions of the article.
• People
  - Nature Biotechnology 27(10):958 (2009)
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