May 2009 Volume 15 Number 5, pp 463 - 584
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NATURE MEDICINE PODCAST
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Making the bench accessible
Listen in to find out how scientists are overcoming disabilities in the lab and for a recap of the biggest headlines in biomedicine.
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EDITORIALS
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A really serious conflict pp463 - 464
Not all financial interests in drug discovery are detrimental, and many are essential for its success. But focusing on perceived conflicts of interest may cause true scientific corruption to go unnoticed.
doi:10.1038/nm0509-463
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Autism and other developmental brain disorders p464
The Second Roche-Nature Medicine Translational Neuroscience Symposium on Autism and other developmental brain disorders was a resounding success.
doi:10.1038/nm0509-464
http://links.ealert.nature.com/ctt?kn=81&m=32895417&r=MTc2NTQyNDEzOQS2&b=2&j=NDg1NDYzNjIS1&mt=1&rt=0
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NEWS
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A master's degree with a business spin gains popularity p465
Genevive Bjorn
doi:10.1038/nm0509-465
http://links.ealert.nature.com/ctt?kn=78&m=32895417&r=MTc2NTQyNDEzOQS2&b=2&j=NDg1NDYzNjIS1&mt=1&rt=0
FDA leadership picks may stress safety over swift approval p466
Kirsten Dorans
doi:10.1038/nm0509-466a
http://links.ealert.nature.com/ctt?kn=92&m=32895417&r=MTc2NTQyNDEzOQS2&b=2&j=NDg1NDYzNjIS1&mt=1&rt=0
Profit-hungry pharma sees some biotechs as ripe for the picking p466
Cassandra Willyard
doi:10.1038/nm0509-466b
http://links.ealert.nature.com/ctt?kn=56&m=32895417&r=MTc2NTQyNDEzOQS2&b=2&j=NDg1NDYzNjIS1&mt=1&rt=0
Flush with new funds, NIH faces challenges of distribution p467
Cassandra Willyard
doi:10.1038/nm0509-467a
http://links.ealert.nature.com/ctt?kn=133&m=32895417&r=MTc2NTQyNDEzOQS2&b=2&j=NDg1NDYzNjIS1&mt=1&rt=0
Will a robot steal your job? p467
Kirsten Dorans
doi:10.1038/nm0509-467b
http://links.ealert.nature.com/ctt?kn=182&m=32895417&r=MTc2NTQyNDEzOQS2&b=2&j=NDg1NDYzNjIS1&mt=1&rt=0
Studies comparing treatment options receive a boost p468
Prashant Nair
doi:10.1038/nm0509-468a
http://links.ealert.nature.com/ctt?kn=64&m=32895417&r=MTc2NTQyNDEzOQS2&b=2&j=NDg1NDYzNjIS1&mt=1&rt=0
Battle lines drawn as US moves toward generic biologics p468
Meredith Wadman
doi:10.1038/nm0509-468b
http://links.ealert.nature.com/ctt?kn=74&m=32895417&r=MTc2NTQyNDEzOQS2&b=2&j=NDg1NDYzNjIS1&mt=1&rt=0
New center aims to speed drug discovery p468
Kirsten Dorans
doi:10.1038/nm0509-468c
http://links.ealert.nature.com/ctt?kn=30&m=32895417&r=MTc2NTQyNDEzOQS2&b=2&j=NDg1NDYzNjIS1&mt=1&rt=0
Regulators confront blind spots in research oversight p469
Alan Dove
doi:10.1038/nm0509-469a
http://links.ealert.nature.com/ctt?kn=120&m=32895417&r=MTc2NTQyNDEzOQS2&b=2&j=NDg1NDYzNjIS1&mt=1&rt=0
Corrigendum: The curious case of clioquinol p469
Lauren Cahoon
doi:10.1038/nm0509-469b
http://links.ealert.nature.com/ctt?kn=164&m=32895417&r=MTc2NTQyNDEzOQS2&b=2&j=NDg1NDYzNjIS1&mt=1&rt=0
Unique TB-HIV research institute planned in South Africa p470
Karen Dente
doi:10.1038/nm0509-470a
http://links.ealert.nature.com/ctt?kn=173&m=32895417&r=MTc2NTQyNDEzOQS2&b=2&j=NDg1NDYzNjIS1&mt=1&rt=0
Coast IRB hits treacherous waters p470
Alan Dove
doi:10.1038/nm0509-470b
http://links.ealert.nature.com/ctt?kn=1&m=32895417&r=MTc2NTQyNDEzOQS2&b=2&j=NDg1NDYzNjIS1&mt=1&rt=0
Amidst scientific unrest, France mulls an institutional alliance p471
Karen Dente
doi:10.1038/nm0509-471a
http://links.ealert.nature.com/ctt?kn=79&m=32895417&r=MTc2NTQyNDEzOQS2&b=2&j=NDg1NDYzNjIS1&mt=1&rt=0
New animal directive moves forward p471
Daniel Cressey
doi:10.1038/nm0509-471b
http://links.ealert.nature.com/ctt?kn=152&m=32895417&r=MTc2NTQyNDEzOQS2&b=2&j=NDg1NDYzNjIS1&mt=1&rt=0
News in brief pp472 - 473
doi:10.1038/nm0509-472
http://links.ealert.nature.com/ctt?kn=171&m=32895417&r=MTc2NTQyNDEzOQS2&b=2&j=NDg1NDYzNjIS1&mt=1&rt=0
Straight talk with...Harvey Fineberg pp474 - 475
Prashant Nair
doi:10.1038/nm0509-474
Abstract: http://links.ealert.nature.com/ctt?kn=86&m=32895417&r=MTc2NTQyNDEzOQS2&b=2&j=NDg1NDYzNjIS1&mt=1&rt=0
Article: http://links.ealert.nature.com/ctt?kn=151&m=32895417&r=MTc2NTQyNDEzOQS2&b=2&j=NDg1NDYzNjIS1&mt=1&rt=0
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NEWS FEATURE
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Breakthroughs Within Reach pp476 - 479
Basic laboratory procedures can present physical challenges for biomedical researchers with disabilities. But a cadre of innovators has come up with technological solutions that make the laboratory bench more accessible to scientists with impaired sight or movement. Stu Hutson reports on how these adaptive research tools help people with disabilities by using everything from computer screen readers to security lasers.
Stu Hutson
doi:10.1038/nm0509-476
http://links.ealert.nature.com/ctt?kn=50&m=32895417&r=MTc2NTQyNDEzOQS2&b=2&j=NDg1NDYzNjIS1&mt=1&rt=0
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BOOK REVIEW
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Studying insomnia p481
Claudio L Bassetti reviews Insomniac by Gayle Greene
doi:10.1038/nm0509-481
http://links.ealert.nature.com/ctt?kn=47&m=32895417&r=MTc2NTQyNDEzOQS2&b=2&j=NDg1NDYzNjIS1&mt=1&rt=0
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CORRESPONDENCE
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Interleukin-17A is not expressed by CD207+ cells in Langerhans cell histiocytosis lesions pp483 - 484
Carl E Allen and Kenneth L McClain
doi:10.1038/nm0509-483
http://links.ealert.nature.com/ctt?kn=23&m=32895417&r=MTc2NTQyNDEzOQS2&b=2&j=NDg1NDYzNjIS1&mt=1&rt=0
Interleukin-17A is not expressed by CD207+ cells in Langerhans cell histiocytosis lesions pp484 - 485
Maurizio Arico, Jan-Inge Henter, R Maarten Egeler and Christine Delprat
doi:10.1038/nm0509-484
http://links.ealert.nature.com/ctt?kn=51&m=32895417&r=MTc2NTQyNDEzOQS2&b=2&j=NDg1NDYzNjIS1&mt=1&rt=0
One size does fit all p485
Katy Taylor
doi:10.1038/nm0509-485
http://links.ealert.nature.com/ctt?kn=174&m=32895417&r=MTc2NTQyNDEzOQS2&b=2&j=NDg1NDYzNjIS1&mt=1&rt=0
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NEWS AND VIEWS
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Blood pressure control: salt gets under your skin pp487 - 488
After an increase in dietary salt, the excess sodium is stored under the skin[mdash]stimulating lymphatic growth through the activity of macrophages (pages 545-552). The findings should recast thinking about how blood pressure is regulated.
Paul J Marvar, Frank J Gordon and David G Harrison
doi:10.1038/nm0509-487
http://links.ealert.nature.com/ctt?kn=165&m=32895417&r=MTc2NTQyNDEzOQS2&b=2&j=NDg1NDYzNjIS1&mt=1&rt=0
Breaking the gene barrier in schizophrenia pp488 - 490
Studies of schizophrenia have been plagued by shortcomings such as weak genetic association with disease, inadequate animal models and limited replication of gene expression findings. Future success may lie not in overcoming any one of these limitations but in a broad approach strengthening the evidence in each area. Using such an approach, neuroscientists have uncovered a new gene behind the disease (pages 509-518).
Szatmar Horvath and Karoly Mirnics
doi:10.1038/nm0509-488
http://links.ealert.nature.com/ctt?kn=106&m=32895417&r=MTc2NTQyNDEzOQS2&b=2&j=NDg1NDYzNjIS1&mt=1&rt=0
Chaos in the embryo pp490 - 491
The chromosomes of human embryos seem to be more unstable than previously thought. An analysis of embryos derived from in vitro fertilization reveals high rates of structural abnormalities (pages 577-583).
David H Ledbetter
doi:10.1038/nm0509-490
http://links.ealert.nature.com/ctt?kn=94&m=32895417&r=MTc2NTQyNDEzOQS2&b=2&j=NDg1NDYzNjIS1&mt=1&rt=0
Angiogenesis: escape from hypoxia pp491 - 493
Current attempts to block angiogenesis during cancer and other diseases are limited partly by their effects on normal angiogenic processes. Could a more targeted approach emerge from the identification of a factor required for pathological angiogenesis under conditions of hypoxia (pages 553-558)?
Mathew L Coleman and Peter J Ratcliffe
doi:10.1038/nm0509-491
http://links.ealert.nature.com/ctt?kn=176&m=32895417&r=MTc2NTQyNDEzOQS2&b=2&j=NDg1NDYzNjIS1&mt=1&rt=0
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COMMUNITY CORNER
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Follicle of youth p495
doi:10.1038/nm0509-495
http://links.ealert.nature.com/ctt?kn=146&m=32895417&r=MTc2NTQyNDEzOQS2&b=2&j=NDg1NDYzNjIS1&mt=1&rt=0
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BETWEEN BEDSIDE AND BENCH
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The immune response goes haywire during sepsis, a deadly condition triggered by infection. Richard S. Hotchkiss and his colleagues take the focus off of the prevailing view that the key aspect of this response is an exuberant inflammatory reaction. They assess recent human studies bolstering the notion that immunosuppression is also a major contributor to the disease. Many people with sepsis succumb to cardiac dysfunction, a process examined by Peter Ward. He showcases the factors that cause cardiomyocyte contractility to wane during the disease.
The sepsis seesaw: tilting toward immunosuppression pp496 - 497
Richard S Hotchkiss, Craig M Coopersmith, Jonathan E McDunn and Thomas A Ferguson
doi:10.1038/nm0509-496
http://links.ealert.nature.com/ctt?kn=160&m=32895417&r=MTc2NTQyNDEzOQS2&b=2&j=NDg1NDYzNjIS1&mt=1&rt=0
The sepsis seesaw: seeking a heart salve pp497 - 498
Peter A Ward
doi:10.1038/nm0509-497
http://links.ealert.nature.com/ctt?kn=70&m=32895417&r=MTc2NTQyNDEzOQS2&b=2&j=NDg1NDYzNjIS1&mt=1&rt=0
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RESEARCH HIGHLIGHTS
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Research Highlights pp500 - 501
doi:10.1038/nm0509-500
http://links.ealert.nature.com/ctt?kn=145&m=32895417&r=MTc2NTQyNDEzOQS2&b=2&j=NDg1NDYzNjIS1&mt=1&rt=0
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COMMENTARY
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Open innovation networks between academia and industry: an imperative for breakthrough therapies pp502 - 507
Teri Melese, Salima M Lin, Julia L Chang and Neal H Cohen
doi:10.1038/nm0509-502
http://links.ealert.nature.com/ctt?kn=185&m=32895417&r=MTc2NTQyNDEzOQS2&b=2&j=NDg1NDYzNjIS1&mt=1&rt=0
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ARTICLES
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A primate-specific, brain isoform of KCNH2 affects cortical physiology, cognition, neuronal repolarization and risk of schizophrenia pp509 - 518
Polymorphisms in a primate-specific isoform of K+ channel KCNH2 are associated with schizophrenia. This isoform induces a rapidly deactivating K+ current and high-frequency neuronal firing pattern. The disease-associated alleles predict lower intelligence quotient scores, lower speed of cognitive processing and altered memory. This channel isoform represents a potential new drug target for psychotherapypages 488-490.
Stephen J Huffaker et al.
doi:10.1038/nm.1962
Abstract: http://links.ealert.nature.com/ctt?kn=4&m=32895417&r=MTc2NTQyNDEzOQS2&b=2&j=NDg1NDYzNjIS1&mt=1&rt=0
Article: http://links.ealert.nature.com/ctt?kn=20&m=32895417&r=MTc2NTQyNDEzOQS2&b=2&j=NDg1NDYzNjIS1&mt=1&rt=0
Endothelial basement membrane laminin [alpha]5 selectively inhibits T lymphocyte extravasation into the brain pp519 - 527
T cells must enter the brain to induce the autoimmune disease multiple sclerosis. Lydia Sorokin and her colleagues identify a mechanism by which T cells migrate across the endothelial basement membrane, a key step to their passage from the blood into the brain.
Chuan Wu et al.
doi:10.1038/nm.1957
Abstract: http://links.ealert.nature.com/ctt?kn=90&m=32895417&r=MTc2NTQyNDEzOQS2&b=2&j=NDg1NDYzNjIS1&mt=1&rt=0
Article: http://links.ealert.nature.com/ctt?kn=2&m=32895417&r=MTc2NTQyNDEzOQS2&b=2&j=NDg1NDYzNjIS1&mt=1&rt=0
Adjuvant IL-7 antagonizes multiple cellular and molecular inhibitory networks to enhance immunotherapies pp528 - 536
Interleukin-7 (IL-7) promotes immune responses and has been touted as a potential tool for improving immune targeting of tumors. Here Pellegrini et al. investigate the mechanisms by which IL-7 increases antitumor responses and the treatment strategies necessary to optimize its effects.
Marc Pellegrini et al.
doi:10.1038/nm.1953
Abstract: http://links.ealert.nature.com/ctt?kn=45&m=32895417&r=MTc2NTQyNDEzOQS2&b=2&j=NDg1NDYzNjIS1&mt=1&rt=0
Article: http://links.ealert.nature.com/ctt?kn=88&m=32895417&r=MTc2NTQyNDEzOQS2&b=2&j=NDg1NDYzNjIS1&mt=1&rt=0
Synthetic EthR inhibitors boost antituberculous activity of ethionamide pp537 - 544
Several tuberculosis drugs are prodrugs that have to be enzymatically activated during metabolism. Ethionamide is such a drug and is activated by the monooxygenase EthA. EthA is itself regulated by the transcriptional repressor EthR. Here Alain Baulard and his colleagues have designed inhibitors of EthR that boost the antimycobacterial efficacy of ethionamide both in vitro and in vivo. Current therapy with ethionamide requires the use of high doses, often eliciting side effects. Its combination with the EthR repressor should allow lower doses to be used.
Nicolas Willand et al.
doi:10.1038/nm.1950
Abstract: http://links.ealert.nature.com/ctt?kn=129&m=32895417&r=MTc2NTQyNDEzOQS2&b=2&j=NDg1NDYzNjIS1&mt=1&rt=0
Article: http://links.ealert.nature.com/ctt?kn=183&m=32895417&r=MTc2NTQyNDEzOQS2&b=2&j=NDg1NDYzNjIS1&mt=1&rt=0
Macrophages regulate salt-dependent volume and blood pressure by a vascular endothelial growth factor-C-dependent buffering mechanism pp545 - 552
Salt intake is associated with hypertension, but the mechanisms by which salt affects blood pressure remain unclear. Agnes Machnik et al. now show that mononuclear cells such as macrophages respond to dietary salt intake by producing the growth factor VEGF-C, leading to expansion of the lymphatic capillary network. Interference with this response in rats fed a high-salt diet exacerbates the increase in blood pressure caused by a high-salt dietpages 487-488..
Agnes Machnik et al.
doi:10.1038/nm.1960
Abstract: http://links.ealert.nature.com/ctt?kn=122&m=32895417&r=MTc2NTQyNDEzOQS2&b=2&j=NDg1NDYzNjIS1&mt=1&rt=0
Article: http://links.ealert.nature.com/ctt?kn=35&m=32895417&r=MTc2NTQyNDEzOQS2&b=2&j=NDg1NDYzNjIS1&mt=1&rt=0
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LETTERS
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Histone H2AX is integral to hypoxia-driven neovascularization pp553 - 558
Hypoxia-triggered neovascularization occurs in many types of disease. Endothelial cells must be able to cope with hypoxic stress, which in other cell types can induce a DNA repair response and inhibit replication. Matina Economopoulou et al. now show that hypoxia induces the generation of a hallmark of the DNA repair response, phosphorylated histone H2AX, in proliferating endothelial cells and that H2AX function is required for neovascularization under hypoxic or ischemic conditions in vivopages 491-493..
Matina Economopoulou et al.
doi:10.1038/nm.1947
Abstract: http://links.ealert.nature.com/ctt?kn=76&m=32895417&r=MTc2NTQyNDEzOQS2&b=2&j=NDg1NDYzNjIS1&mt=1&rt=0
Article: http://links.ealert.nature.com/ctt?kn=143&m=32895417&r=MTc2NTQyNDEzOQS2&b=2&j=NDg1NDYzNjIS1&mt=1&rt=0
Copy number analysis indicates monoclonal origin of lethal metastatic prostate cancer pp559 - 565
Primary prostate cancer is genomically highly heterogeneous and is thought to derive from multiple independent clones of cancer cells. Using high-resolution genomic analyses, Bova et al. now show that, in contrast to primary tumors, metastases are monoclonal, originating from a single cancer cell. These findings call into question current views of the origins of primary prostate cancer and suggest that the genomic profile of prostate cancer metastases should inform therapeutic decisions.
Wennuan Liu et al.
doi:10.1038/nm.1944
Abstract: http://links.ealert.nature.com/ctt?kn=91&m=32895417&r=MTc2NTQyNDEzOQS2&b=2&j=NDg1NDYzNjIS1&mt=1&rt=0
Article: http://links.ealert.nature.com/ctt?kn=17&m=32895417&r=MTc2NTQyNDEzOQS2&b=2&j=NDg1NDYzNjIS1&mt=1&rt=0
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TECHNICAL REPORTS
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Nanofluidic proteomic assay for serial analysis of oncoprotein activation in clinical specimens pp566 - 571
Alice C Fan et al.
doi:10.1038/nm.1903
Abstract: http://links.ealert.nature.com/ctt?kn=58&m=32895417&r=MTc2NTQyNDEzOQS2&b=2&j=NDg1NDYzNjIS1&mt=1&rt=0
Article: http://links.ealert.nature.com/ctt?kn=33&m=32895417&r=MTc2NTQyNDEzOQS2&b=2&j=NDg1NDYzNjIS1&mt=1&rt=0
The parametric response map is an imaging biomarker for early cancer treatment outcome pp572 - 576
Craig J Galban et al.
doi:10.1038/nm.1919
Abstract: http://links.ealert.nature.com/ctt?kn=52&m=32895417&r=MTc2NTQyNDEzOQS2&b=2&j=NDg1NDYzNjIS1&mt=1&rt=0
Article: http://links.ealert.nature.com/ctt?kn=77&m=32895417&r=MTc2NTQyNDEzOQS2&b=2&j=NDg1NDYzNjIS1&mt=1&rt=0
Chromosome instability is common in human cleavage-stage embryos pp577 - 583
Evelyne Vanneste et al.
doi:10.1038/nm.1924
Abstract: http://links.ealert.nature.com/ctt?kn=43&m=32895417&r=MTc2NTQyNDEzOQS2&b=2&j=NDg1NDYzNjIS1&mt=1&rt=0
Article: http://links.ealert.nature.com/ctt?kn=85&m=32895417&r=MTc2NTQyNDEzOQS2&b=2&j=NDg1NDYzNjIS1&mt=1&rt=0
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CORRIGENDA
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Corrigendum: Regulation of cardiovascular development and integrity by the heart of glass- cerebral cavernous malformation protein pathway p584
Benjamin Kleaveland et al.
doi:10.1038/nm0509-584a
http://links.ealert.nature.com/ctt?kn=139&m=32895417&r=MTc2NTQyNDEzOQS2&b=2&j=NDg1NDYzNjIS1&mt=1&rt=0
Corrigendum: A pivotal role for galectin-1 in fetomaternal tolerance p584
Sandra M Blois et al.
doi:10.1038/nm0509-584b
http://links.ealert.nature.com/ctt?kn=167&m=32895417&r=MTc2NTQyNDEzOQS2&b=2&j=NDg1NDYzNjIS1&mt=1&rt=0
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