Table of contents


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Editorial

The worst of times, the best of times p101

doi:10.1038/nbt0209-101

Big pharma should be more proactively investing in cash-hungry public biotech companies.


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News

Venture capital shifts strategies, startups suffer pp103 - 104

Peter Mitchell

doi:10.1038/nbt0209-103


Merck joins the biotech game p104

Victor Bethencourt

doi:10.1038/nbt0209-104



Osiris seals billion-dollar deal with Genzyme for cell therapy pp106 - 107

George S. Mack

doi:10.1038/nbt0209-106


GM poplars to grow next door p107

Hayley Birch

doi:10.1038/nbt0209-107a


FDA goes public-friendly p107

Emily Waltz

doi:10.1038/nbt0209-107b


Avastin-Tarceva combination fails in lung cancer pp108 - 109

Dan Jones

doi:10.1038/nbt0209-108


Stem cells caught in morality clause p109

Nayanah Siva

doi:10.1038/nbt0209-109a


Land use stirs biofuels ruckus p109

Susan Kim

doi:10.1038/nbt0209-109b


Cuba's first GM corn p110

Veronica Guerrero

doi:10.1038/nbt0209-110a


EU pushes advanced therapies p110

Susan Aldridge

doi:10.1038/nbt0209-110b


FDA holds court on post hoc data linking KRAS status to drug response pp110 - 112

George S. Mack

doi:10.1038/nbt0209-110c


Data Page

2008—down, but not out p113

Walter Yang

doi:10.1038/nbt0209-113


News Feature

Glial cells on the radar pp114 - 116

Cormac Sheridan

doi:10.1038/nbt0209-114

Long thought of as passive bystanders, glial cells are coming under increasing scrutiny as mediators of inflammatory disease in the nervous system. Now, some drug makers are hoping they can be targeted pharmacologically. Cormac Sheridan reports.


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Bioentrepreneur

Building a business

Avoiding the obvious pp117 - 119

Sherry L Murphy & Kenneth D Sibley

doi:10.1038/bioe.2008.12


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Opinion and Comment

Correspondence

The next generation p120

Fern Wickson

doi:10.1038/nbt0209-120a


The next generation pp120 - 121

Justin Chakma

doi:10.1038/nbt0209-120b


Gunvalson and PTC Therapeutics' community outreach pp121 - 122

Stuart W Peltz

doi:10.1038/nbt0209-121


DNA sequence patents are not in the grave yet p122

Robert Cook-Deegan & Arti K Rai

doi:10.1038/nbt0209-122


Commentary

A lifeline for the biotech sector pp123 - 124

Mark Kessel

doi:10.1038/nbt0209-123

With many small biotech companies teetering at the edge of a financial precipice, the US government should act swiftly to enact tax benefits allowing a refund of net operating losses.


Charting a course through a perfect storm pp125 - 127

Arthur Klausner

doi:10.1038/nbt0209-125

A venture capitalist gives his perspective on the outlook for life sciences ventures amid the perfect storm of the current economic downturn.


Book Review

The bioentrepreneur's road map p128

doi:10.1038/nbt0209-128


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Features

The cancer vaccine roller coaster pp129 - 139

Bruce Goldman & Laura DeFrancesco

doi:10.1038/nbt0209-129

The cancer vaccine field is littered with promising products that failed to show clinical efficacy. Could it finally be on the verge of a first US approval?


Patents

Proprietary science, open science and the role of patent disclosure: the case of zinc-finger proteins pp140 - 144

Subhashini Chandrasekharan, Sapna Kumar, Cory M Valley & Arti Rai

doi:10.1038/nbt0209-140

A closer look at the large patent estate now covering both the engineering and use of zinc-finger proteins.


Recent patent applications in gene expression p145

doi:10.1038/nbt0209-145


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News and Views

Year of the ox pp146 - 147

Yann Echelard

doi:10.1038/nbt0209-146

High levels of human polyclonal antibodies have been produced in a transgenic large animal.

See also: Research by Kuroiwa et al.


One photon up, one photon down pp147 - 148

Enrico Gratton & Michelle Digman

doi:10.1038/nbt0209-147

A microscopy technique based on stimulated Raman scattering achieves label-free imaging with very high sensitivity.


Knocking sense into regulatory pathways pp149 - 150

Guri Giaever & Corey Nislow

doi:10.1038/nbt0209-149

Simultaneous targeted perturbations illuminate the structure and function of regulatory networks.


Sequencing in real time pp150 - 151

Michael L Metzker

doi:10.1038/nbt0209-150

DNA synthesis by single polymerase molecules has been visualized at the speed of catalysis, heralding a new sequencing technology of unparalleled throughput.


Research highlights p152

doi:10.1038/nbt0209-152


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Computational Biology

Primer

Understanding genome browsing pp153 - 155

Melissa S Cline & W James Kent

doi:10.1038/nbt0209-153

How can genome browsers help researchers to infer biological knowledge from data that might be misleading?


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Research

Review

Protein promiscuity and its implications for biotechnology pp157 - 167

Irene Nobeli, Angelo D Favia & Janet M Thornton

doi:10.1038/nbt1519


Brief Communications

Transgenic mice with defined combinations of drug-inducible reprogramming factors pp169 - 171

Styliani Markoulaki, Jacob Hanna, Caroline Beard, Bryce W Carey, Albert W Cheng, Christopher J Lengner, Jessica A Dausman, Dongdong Fu, Qing Gao, Su Wu, John P Cassady & Rudolf Jaenisch

doi:10.1038/nbt.1520

The generation of induced pluripotent stem cells might be improved by replacing the reprogramming transgenes with small molecules. To provide cells suitable for small-molecule screening, Markoulaki et al. segregate the transgenes Oct4, Sox2, Klf4 and c-Myc through breeding, creating mice carrying all possible combinations of the four factors.


Articles

Antigen-specific human polyclonal antibodies from hyperimmunized cattle pp173 - 181

Yoshimi Kuroiwa, Poothappillai Kasinathan, Thillainayagen Sathiyaseelan, Jin-an Jiao, Hiroaki Matsushita, Janaki Sathiyaseelan, Hua Wu, Jenny Mellquist, Melissa Hammitt, Julie Koster, Satoru Kamoda, Katsumi Tachibana, Isao Ishida & James M Robl

doi:10.1038/nbt.1521

A reliable supply of antigen-specific human antibodies could be useful for treating many diseases. Kuroiwa et al. use multiple rounds of genetic modification and cloning to generate a calf carrying human immunoglobulin genes and lacking bovine immunoglobulin genes, and show that the hyperimmunized animal produces >2 g/l of antigen-specific human polyclonal antibodies.

See also: News and Views by Echelard


Solution hybrid selection with ultra-long oligonucleotides for massively parallel targeted sequencing pp182 - 189

Andreas Gnirke, Alexandre Melnikov, Jared Maguire, Peter Rogov, Emily M LeProust, William Brockman, Timothy Fennell, Georgia Giannoukos, Sheila Fisher, Carsten Russ, Stacey Gabriel, David B Jaffe, Eric S Lander & Chad Nusbaum

doi:10.1038/nbt.1523

Gnirke et al. present a bead-based method for capturing sequences of interest in the human genome for massively parallel sequencing. Using long, biotinylated RNA probes to pull down PCR-amplified DNA fragments, they demonstrate sequencing of 2.5 Mbs of exons in 1,900 genes.


Prediction of high-responding peptides for targeted protein assays by mass spectrometry pp190 - 198

Vincent A Fusaro, D R Mani, Jill P Mesirov & Steven A Carr

doi:10.1038/nbt.1524

Development of sensitive mass spectrometry–based assays for complex biofluids depends on the ability to identify signature peptides that produce the strongest signals. Fusaro et al. use protein physicochemical properties to predict high-responding peptides in data obtained from complex samples such as plasma.


Letter

Dynamic modularity in protein interaction networks predicts breast cancer outcome pp199 - 204

Ian W Taylor, Rune Linding, David Warde-Farley, Yongmei Liu, Catia Pesquita, Daniel Faria, Shelley Bull, Tony Pawson, Quaid Morris & Jeffrey L Wrana

doi:10.1038/nbt.1522

Altered gene expression in tumors has been explored as a prognostic indicator of cancer outcome and treatment efficacy. Taylor et al. extend this approach by analyzing the coordinated expression of 'hub' proteins and their interacting partners as a means of predicting breast cancer prognosis.


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Corrigendum

Corrigendum: What's fueling the biotech engine—2007 p205

Saurabh Aggarwal

doi:10.1038/nbt0209-205a


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Errata

Erratum: What's fueling the biotech engine—2007 p205

Saurabh Aggarwal

doi:10.1038/nbt0209-205b


Erratum: Asymmetric RNA duplexes mediate RNA interference in mammalian cells p205

Xiangao Sun, Harry A Rogoff & Chiang J Li

doi:10.1038/nbt0209-205c


Erratum: Profile: Alan Alda p205

George S Mack

doi:10.1038/nbt0209-205d


Erratum: Biotech sector ponders potential 'bloodbath' p205

Peter Mitchell & Brady Huggett

doi:10.1038/nbt0209-205e


Erratum: Doubts surround link between Bt cotton failure and farmer suicide p205

Cormac Sheridan

doi:10.1038/nbt0209-205f


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Naturejobs

Careers and Recruitment

Fear factor pp206 - 207

Genevive Bjorn

doi:10.1038/nbt0209-206

Job prospects are looking gloomy as the economic downturn runs its course, but there are bright spots for some.


People

People p208

doi:10.1038/nbt0209-208


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