Hot off the presses! May 01 Nat Biotechnol

The May 01 issue of the Nat Biotechnol is now up on Pubget (About Nat Biotechnol): 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:

• A strike against preemption
  - Nat Biotechnol 27(5):397 (2009)
  Industry has been warned: US Food and Drug Administration (FDA) approval is no shield against failure-to-warn or product-liability suits.
• Wyeth preemption case ruling sparks labeling confusion
  - Nat Biotechnol 27(5):399-400 (2009)
  
• Health under DeParle and Sebelius
  - Nat Biotechnol 27(5):400 (2009)
  
• Google spawns venture fund
  - Nat Biotechnol 27(5):400 (2009)
  
• Cash infusion for HIV microbicides
  - Nat Biotechnol 27(5):401-402 (2009)
  
• Corporate venture funds chase early-stage deals
  - Nat Biotechnol 27(5):403-404 (2009)
  
• Mexico OKs GM corn
  - Nat Biotechnol 27(5):404 (2009)
  
• Biotech fat cats
  - Nat Biotechnol 27(5):404 (2009)
  
• FDA on warpath for Google links
  - Nat Biotechnol 27(5):405 (2009)
  
• Healthcare reform looms, firms seek scraps from US stimulus
  - Nat Biotechnol 27(5):406-408 (2009)
  
• Chugai reports Actemra deaths
  - Nat Biotechnol 27(5):407 (2009)
  
• Irish biotech buoyant
  - Nat Biotechnol 27(5):408 (2009)
  
• Hospital to genotype all tumors
  - Nat Biotechnol 27(5):408 (2009)
  
• Richard Gold
  - Nat Biotechnol 27(5):409 (2009)
  Lawyer Richard Gold argues that superfluous patents stifle innovation. Industry should adopt new models, he says, in which knowledge is viewed as a club good.
• Biotech braves the winter in 1Q09
  - Nat Biotechnol 27(5):410 (2009)
  
• Academia and the company coin
  - Nat Biotechnol 27(5):411-414 (2009)
  As the economic downturn chokes spin-outs from academia, a spate of newly minted university-industry partnerships are springing up. Failing to address the financial conflicts in such partnerships could spell trouble for both faculty and drug companies. Jim Kling investigates.
• Prepare to meet your partner
  - Nat Biotechnol 27(5):415-418 (2009)
  
• Regulating laboratory-developed tests
  - Nat Biotechnol 27(5):419 (2009)
  
• Regulating laboratory-developed tests
  - Nat Biotechnol 27(5):419-420 (2009)
  
• Regulating laboratory-developed tests
  - Nat Biotechnol 27(5):420-421 (2009)
  
• Regulating laboratory-developed tests
  - Nat Biotechnol 27(5):421 (2009)
  
• In need of a reality check
  - Nat Biotechnol 27(5):422 (2009)
  
• Gilead's deal of a lifetime
  - Nat Biotechnol 27(5):423 (2009)
  Gilead Sciences' ascent to the upper echelon of biotech centered around one very savvy acquisition that launched an HIV franchise.
• Proceeding in a receding economy
  - Nat Biotechnol 27(5):424-425 (2009)
  The biotech sector must not only maintain an emphasis on ground-breaking products and focus on retaining key staff but also mobilize to ensure that US health policy continues to reward its innovations.
• Be reasonable
  - Nat Biotechnol 27(5):426 (2009)
  
• Small but tenacious: South Africa's health biotech sector
  - Nat Biotechnol 27(5):427-445 (2009)
  Despite a challenging business environment, entrepreneurial health biotech companies in South Africa are finding ways to succeed.
• Combine and conquer: handling biotech combination inventions in the wake of KSR
  - Nat Biotechnol 27(5):446-448 (2009)
  To what extent will KSR limit combination inventions in biotech?
• Recent patent applications in biological imaging
  - Nat Biotechnol 27(5):449 (2009)
  
• Overpowering the component problem
  - Nat Biotechnol 27(5):450-451 (2009)
  Synthetic gene networks can be readily redesigned using new libraries of quantitatively characterized promoters coupled with predictive mathematical modeling.
• Expanded CAG repeats in the crosshairs
  - Nat Biotechnol 27(5):451-452 (2009)
  Antisense oligomers targeted to CAG repeats allow allele-specific knockdown of the gene that causes Huntington's disease.
• Targeted instant immunity
  - Nat Biotechnol 27(5):452-453 (2009)
  Antibodies can be programmed to bind cancer cells using covalently binding antigens and adapters.
• Research highlights
  - Nat Biotechnol 27(5):454 (2009)
  
• How to map billions of short reads onto genomes
  - Nat Biotechnol 27(5):455-457 (2009)
  Mapping the vast quantities of short sequence fragments produced by next-generation sequencing platforms is a challenge. What programs are available and how do they work?
• Embryonic stem cell–specific microRNAs promote induced pluripotency
  - Nat Biotechnol 27(5):459-461 (2009)
  This report demonstrates that introduction of microRNAs (miRNAs) specific to embryonic stem cells enhances the production of mouse induced pluripotent stem (iPS) cells. The miRNAs miR-291-3p, miR-294 and miR-295 increase the efficiency of reprogramming by Oct4, Sox2 and Klf4, but not by these factors plus cMyc. cMyc binds the promoter of the miRNAs, suggesting that they are downstream effectors of cMyc during reprogramming. However, unlike cMyc, the miRNAs induce a homogeneous population of iPS cell colonies.
• Antibacterial discovery in actinomycetes strains with mutations in RNA polymerase or ribosomal protein S12
  - Nat Biotechnol 27(5):462-464 (2009)
  We show that selection of drug-resistant bacterial mutants allows the discovery of antibacterial compounds. Mutant strains of a soil-isolated Streptomyces species that does not produce antibacterials synthesize a previously unknown class of antibacterial, which we name piperidamycin. Overall, 6% of non-Streptomyces actinomycetes species and 43% of Streptomyces species that do not produce antibacterials are activated to produce them. The antibacterial-producing mutants all carried mutations in RNA polymerase and/or the ribosomal protein S12.
• Diversity-based, model-guided construction of synthetic gene networks with predicted functions
  - Nat Biotechnol 27(5):465-471 (2009)
  Engineering artificial gene networks from modular components is a major goal of synthetic biology. However, the construction of gene networks with predictable functions remains hampered by a lack of suitable components and the fact that assembled networks often require extensive, iterative retrofitting to work as intended. Here we present an approach that couples libraries of diversified components (synthesized with randomized nonessential sequence) with in silico modeling to guide predictable gene network construction without the need for post hoc tweaking. We demonstrate our approach in Saccharomyces cerevisiae by synthesizing regulatory promoter libraries and using them to construct feed-forward loop networks with different predicted input-output characteristics. We then expand our method to produce a synthetic gene network acting as a predictable timer, modifiable by component choice. We use this network to control the timing of yeast sedimentation, illustrating ho! w the plug-and-play nature of our design can be readily applied to biotechnology.
• Allele-specific silencing of mutant huntingtin and ataxin-3 genes by targeting expanded CAG repeats in mRNAs
  - Nat Biotechnol 27(5):478-484 (2009)
  Expanded trinucleotide repeats1 cause many neurological diseases. These include Machado-Joseph disease (MJD)2 and Huntington's disease (HD)3, which are caused by expanded CAG repeats within an allele of the ataxin-3 (ATXN3) and huntingtin (HTT) genes, respectively. Silencing expression of these genes is a promising therapeutic strategy, but indiscriminate inhibition of both the mutant and wild-type alleles may lead to toxicity, and allele-specific approaches have required polymorphisms that differ among individuals. We report that peptide nucleic acid and locked nucleic acid antisense oligomers that target CAG repeats can preferentially inhibit mutant ataxin-3 and HTT protein expression in cultured cells. Duplex RNAs were less selective than single-stranded oligomers. The activity of the peptide nucleic acids does not involve inhibition of transcription, and differences in mRNA secondary structure or the number of oligomer binding sites may be important. Antisense olig! omers that discriminate between wild-type and mutant genes on the basis of repeat length may offer new options for developing treatments for MJD, HD and related hereditary diseases.
• Allelic imbalance sequencing reveals that single-nucleotide polymorphisms frequently alter microRNA-directed repression
  - Nat Biotechnol 27(5):472-477 (2009)
  Genetic changes that help explain the differences between two individuals might create or disrupt sites complementary to microRNAs (miRNAs)1, 2, but the extent to which such polymorphic sites influence miRNA-mediated repression is unknown. Here, we describe a method to measure mRNA allelic imbalances associated with a regulatory site found in mRNA transcribed from one allele but not found in that transcribed from the other. Applying this method, called allelic imbalance sequencing, to sites for three miRNAs (miR-1, miR-133 and miR-122) provided quantitative measurements of repression in vivo without altering either the miRNAs or their targets. A substantial fraction of polymorphic sites mediated repression in tissues that expressed the cognate miRNA, and downregulation was correlated with site type and site context. Extrapolating these results to the other broadly conserved miRNAs suggests that when comparing two mouse strains (or two human individuals), polymorphic mi! RNA sites cause expression of many genes (often hundreds) to differ.
• Corrigendum: Highly efficient neural conversion of human ES and iPS cells by dual inhibition of SMAD signaling
  - Nat Biotechnol 27(5):485 (2009)
  
• Corrigendum: Targeted and genome-scale strategies reveal gene-body methylation signatures in human cells
  - Nat Biotechnol 27(5):485 (2009)
  
• Erratum: Biotech patents—business as usual?
  - Nat Biotechnol 27(5):485 (2009)
  
• Erratum: Proprietary science, open science and the role of patent disclosure: the case of zinc-finger proteins
  - Nat Biotechnol 27(5):485 (2009)
  
• Erratum: Biotech scientists bank on big pharma's biologics push
  - Nat Biotechnol 27(5):485 (2009)
  
• Erratum: Identification of selective inhibitors of uncharacterized enzymes by high-throughput screening with fluorescent activity-based probes
  - Nat Biotechnol 27(5):485 (2009)
  
• People
  - Nat Biotechnol 27(5):486 (2009)