A really serious conflict - pp463 - 464

doi:10.1038/nm0509-463

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.

Abstract - | Full Text - A really serious conflict | PDF (267 KB) - A really serious conflict

Autism and other developmental brain disorders - p464

doi:10.1038/nm0509-464

The Second Roche–Nature Medicine Translational Neuroscience Symposium on Autism and other developmental brain disorders was a resounding success.

Abstract - | Full Text - Autism and other developmental brain disorders | PDF (205 KB) - Autism and other developmental brain disorders

A master's degree with a business spin gains popularity - p465

Genevive Bjorn

doi:10.1038/nm0509-465

Full Text - A master's degree with a business spin gains popularity | PDF (150 KB) - A master's degree with a business spin gains popularity

FDA leadership picks may stress safety over swift approval - p466

Kirsten Dorans

doi:10.1038/nm0509-466a

Full Text - FDA leadership picks may stress safety over swift approval | PDF (160 KB) - FDA leadership picks may stress safety over swift approval

Profit-hungry pharma sees some biotechs as ripe for the picking - p466

Cassandra Willyard

doi:10.1038/nm0509-466b

Full Text - Profit-hungry pharma sees some biotechs as ripe for the picking | PDF (160 KB) - Profit-hungry pharma sees some biotechs as ripe for the picking

Flush with new funds, NIH faces challenges of distribution - p467

Cassandra Willyard

doi:10.1038/nm0509-467a

Full Text - Flush with new funds, NIH faces challenges of distribution | PDF (221 KB) - Flush with new funds, NIH faces challenges of distribution

Will a robot steal your job? - p467

Kirsten Dorans

doi:10.1038/nm0509-467b

Full Text - Will a robot steal your job? | PDF (221 KB) - Will a robot steal your job?

Studies comparing treatment options receive a boost - p468

Prashant Nair

doi:10.1038/nm0509-468a

Full Text - Studies comparing treatment options receive a boost | PDF (113 KB) - Studies comparing treatment options receive a boost

Battle lines drawn as US moves toward generic biologics - p468

Meredith Wadman

doi:10.1038/nm0509-468b

Full Text - Battle lines drawn as US moves toward generic biologics | PDF (113 KB) - Battle lines drawn as US moves toward generic biologics

New center aims to speed drug discovery - p468

Kirsten Dorans

doi:10.1038/nm0509-468c

Full Text - New center aims to speed drug discovery | PDF (113 KB) - New center aims to speed drug discovery

Regulators confront blind spots in research oversight - p469

Alan Dove

doi:10.1038/nm0509-469a

Full Text - Regulators confront blind spots in research oversight | PDF (180 KB) - Regulators confront blind spots in research oversight

Corrigendum: The curious case of clioquinol - p469

Lauren Cahoon

doi:10.1038/nm0509-469b

Full Text - Corrigendum: The curious case of clioquinol | PDF (180 KB) - Corrigendum: The curious case of clioquinol

Unique TB-HIV research institute planned in South Africa - p470

Karen Dente

doi:10.1038/nm0509-470a

Full Text - Unique TB-HIV research institute planned in South Africa | PDF (188 KB) - Unique TB-HIV research institute planned in South Africa

Coast IRB hits treacherous waters - p470

Alan Dove

doi:10.1038/nm0509-470b

Full Text - Coast IRB hits treacherous waters | PDF (188 KB) - Coast IRB hits treacherous waters

Amidst scientific unrest, France mulls an institutional alliance - p471

Karen Dente

doi:10.1038/nm0509-471a

Full Text - Amidst scientific unrest, France mulls an institutional alliance | PDF (213 KB) - Amidst scientific unrest, France mulls an institutional alliance

New animal directive moves forward - p471

Daniel Cressey

doi:10.1038/nm0509-471b

Full Text - New animal directive moves forward | PDF (213 KB) - New animal directive moves forward

News in brief - pp472 - 473

doi:10.1038/nm0509-472

Full Text - News in brief | PDF (808 KB) - News in brief

Straight talk with...Harvey Fineberg - pp474 - 475

Prashant Nair

doi:10.1038/nm0509-474

In 1970, the US government chartered the Institute of Medicine (IOM), a component of the National Academies, to serve as an independent counsel on issues concerning health policy. Harvey Fineberg, former provost of Harvard University, has served at the helm of the IOM as the institute's president since 2002. He spoke to Prashant Nair about the role of the IOM in biomedical research in the US.

Abstract - | Full Text - Straight talk with...Harvey Fineberg | PDF (231 KB) - Straight talk with...Harvey Fineberg

Breakthroughs Within Reach - pp476 - 479

Stu Hutson

doi:10.1038/nm0509-476

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.

Abstract - | Full Text - Breakthroughs Within Reach | PDF (1,551 KB) - Breakthroughs Within Reach

Studying insomnia - p481

Claudio L Bassetti reviews Insomniac by Gayle Greene

doi:10.1038/nm0509-481

Full Text - Studying insomnia | PDF (89 KB) - Studying insomnia

Interleukin-17A is not expressed by CD207⁺ cells in Langerhans cell histiocytosis lesions - pp483 - 484

Carl E Allen & Kenneth L McClain

doi:10.1038/nm0509-483

Full Text - Interleukin-17A is not expressed by CD207+ cells in Langerhans cell histiocytosis lesions | PDF (186 KB) - Interleukin-17A is not expressed by CD207+ cells in Langerhans cell histiocytosis lesions | Supplementary information

Interleukin-17A is not expressed by CD207⁺ cells in Langerhans cell histiocytosis lesions - pp484 - 485

Maurizio Arico, Jan-Inge Henter, R Maarten Egeler & Christine Delprat

doi:10.1038/nm0509-484

Full Text - Interleukin-17A is not expressed by CD207+ cells in Langerhans cell histiocytosis lesions | PDF (120 KB) - Interleukin-17A is not expressed by CD207+ cells in Langerhans cell histiocytosis lesions

One size does fit all - p485

Katy Taylor

doi:10.1038/nm0509-485

Full Text - One size does fit all | PDF (79 KB) - One size does fit all

Blood pressure control: salt gets under your skin - pp487 - 488

Paul J Marvar, Frank J Gordon & David G Harrison

doi:10.1038/nm0509-487

After an increase in dietary salt, the excess sodium is stored under the skin—stimulating lymphatic growth through the activity of macrophages (pages 545–552). The findings should recast thinking about how blood pressure is regulated.

Abstract - | Full Text - Blood pressure control: salt gets under your skin | PDF (763 KB) - Blood pressure control: salt gets under your skin

See also: Article by Machnik et al.

Breaking the gene barrier in schizophrenia - pp488 - 490

Szatmár Horváth & Károly Mirnics

doi:10.1038/nm0509-488

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).

Abstract - | Full Text - Breaking the gene barrier in schizophrenia | PDF (449 KB) - Breaking the gene barrier in schizophrenia

See also: Article by Huffaker et al.

Chaos in the embryo - pp490 - 491

David H Ledbetter

doi:10.1038/nm0509-490

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).

Abstract - | Full Text - Chaos in the embryo | PDF (333 KB) - Chaos in the embryo

See also: Technical Report by Vanneste et al.

Angiogenesis: escape from hypoxia - pp491 - 493

Mathew L Coleman & Peter J Ratcliffe

doi:10.1038/nm0509-491

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)?

Abstract - | Full Text - Angiogenesis: escape from hypoxia | PDF (417 KB) - Angiogenesis: escape from hypoxia

See also: Letter by Economopoulou et al.

Follicle of youth - p495

doi:10.1038/nm0509-495

Full Text - Follicle of youth | PDF (212 KB) - Follicle of youth

The sepsis seesaw: tilting toward immunosuppression - pp496 - 497

Richard S Hotchkiss, Craig M Coopersmith, Jonathan E McDunn & Thomas A Ferguson

doi:10.1038/nm0509-496

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.

Abstract - | Full Text - The sepsis seesaw: tilting toward immunosuppression | PDF (162 KB) - The sepsis seesaw: tilting toward immunosuppression

The sepsis seesaw: seeking a heart salve - pp497 - 498

Peter A Ward

doi:10.1038/nm0509-497

Full Text - The sepsis seesaw: seeking a heart salve | PDF (388 KB) - The sepsis seesaw: seeking a heart salve

Research Highlights - pp500 - 501

doi:10.1038/nm0509-500

Full Text - Research Highlights | PDF (265 KB) - Research Highlights

Open innovation networks between academia and industry: an imperative for breakthrough therapies - pp502 - 507

Teri Melese, Salima M Lin, Julia L Chang & Neal H Cohen

doi:10.1038/nm0509-502

Full Text - Open innovation networks between academia and industry: an imperative for breakthrough therapies | PDF (338 KB) - Open innovation networks between academia and industry: an imperative for breakthrough therapies

A primate-specific, brain isoform of KCNH2 affects cortical physiology, cognition, neuronal repolarization and risk of schizophrenia - pp509 - 518

Stephen J Huffaker, Jingshan Chen, Kristin K Nicodemus, Fabio Sambataro, Feng Yang, Venkata Mattay, Barbara K Lipska, Thomas M Hyde, Jian Song, Dan Rujescu, Ina Giegling, Karine Mayilyan, Morgan J Proust, Armen Soghoyan, Grazia Caforio, Joseph H Callicott, Alessandro Bertolino, Andreas Meyer-Lindenberg, Jay Chang, Yuanyuan Ji, Michael F Egan, Terry E Goldberg, Joel E Kleinman, Bai Lu & Daniel R Weinberger

doi:10.1038/nm.1962

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.

Abstract - | Full Text - A primate-specific, brain isoform of KCNH2 affects cortical physiology, cognition, neuronal repolarization and risk of schizophrenia | PDF (1,129 KB) - A primate-specific, brain isoform of KCNH2 affects cortical physiology, cognition, neuronal repolarization and risk of schizophrenia | Supplementary information

See also: News and Views by Horváth & Mirnics

Endothelial basement membrane laminin 5 selectively inhibits T lymphocyte extravasation into the brain - pp519 - 527

Chuan Wu, Fredrik Ivars, Per Anderson, Rupert Hallmann, Dietmar Vestweber, Per Nilsson, Horst Robenek, Karl Tryggvason, Jian Song, Eva Korpos, Karin Loser, Stefan Beissert, Elisabeth Georges-Labouesse & Lydia M Sorokin

doi:10.1038/nm.1957

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.

Abstract - | Full Text - Endothelial basement membrane laminin 5 selectively inhibits T lymphocyte extravasation into the brain | PDF (925 KB) - Endothelial basement membrane laminin 5 selectively inhibits T lymphocyte extravasation into the brain | Supplementary information

Adjuvant IL-7 antagonizes multiple cellular and molecular inhibitory networks to enhance immunotherapies - pp528 - 536

Marc Pellegrini, Thomas Calzascia, Alisha R Elford, Arda Shahinian, Amy E Lin, Dilan Dissanayake, Salim Dhanji, Linh T Nguyen, Matthew A Gronski, Michel Morre, Brigitte Assouline, Katharina Lahl, Tim Sparwasser, Pamela S Ohashi & Tak W Mak

doi:10.1038/nm.1953

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.

Abstract - | Full Text - Adjuvant IL-7 antagonizes multiple cellular and molecular inhibitory networks to enhance immunotherapies | PDF (697 KB) - Adjuvant IL-7 antagonizes multiple cellular and molecular inhibitory networks to enhance immunotherapies | Supplementary information

Synthetic EthR inhibitors boost antituberculous activity of ethionamide - pp537 - 544

Nicolas Willand, Bertrand Dirié, Xavier Carette, Pablo Bifani, Amit Singhal, Matthieu Desroses, Florence Leroux, Eve Willery, Vanessa Mathys, Rebecca Déprez-Poulain, Guy Delcroix, Frédéric Frénois, Marc Aumercier, Camille Locht, Vincent Villeret, Benoit Déprez & Alain R Baulard

doi:10.1038/nm.1950

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.

Abstract - | Full Text - Synthetic EthR inhibitors boost antituberculous activity of ethionamide | PDF (686 KB) - Synthetic EthR inhibitors boost antituberculous activity of ethionamide | Supplementary information

Macrophages regulate salt-dependent volume and blood pressure by a vascular endothelial growth factor-C–dependent buffering mechanism - pp545 - 552

Agnes Machnik, Wolfgang Neuhofer, Jonathan Jantsch, Anke Dahlmann, Tuomas Tammela, Katharina Machura, Joon-Keun Park, Franz-Xaver Beck, Dominik N Müller, Wolfgang Derer, Jennifer Goss, Agata Ziomber, Peter Dietsch, Hubertus Wagner, Nico van Rooijen, Armin Kurtz, Karl F Hilgers, Kari Alitalo, Kai-Uwe Eckardt, Friedrich C Luft, Dontscho Kerjaschki & Jens Titze

doi:10.1038/nm.1960

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..

Abstract - | Full Text - Macrophages regulate salt-dependent volume and blood pressure by a vascular endothelial growth factor-C–dependent buffering mechanism | PDF (714 KB) - Macrophages regulate salt-dependent volume and blood pressure by a vascular endothelial growth factor-C–dependent buffering mechanism | Supplementary information

See also: News and Views by Marvar et al.

Histone H2AX is integral to hypoxia-driven neovascularization - pp553 - 558

Matina Economopoulou, Harald F Langer, Arkady Celeste, Valeria V Orlova, Eun Young Choi, Mingchao Ma, Athanassios Vassilopoulos, Elsa Callen, Chuxia Deng, Craig H Bassing, Manfred Boehm, Andre Nussenzweig & Triantafyllos Chavakis

doi:10.1038/nm.1947

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..

First Paragraph - | Full Text - Histone H2AX is integral to hypoxia-driven neovascularization | PDF (444 KB) - Histone H2AX is integral to hypoxia-driven neovascularization | Supplementary information

See also: News and Views by Coleman & Ratcliffe

Copy number analysis indicates monoclonal origin of lethal metastatic prostate cancer - pp559 - 565

Wennuan Liu, Sari Laitinen, Sofia Khan, Mauno Vihinen, Jeanne Kowalski, Guoqiang Yu, Li Chen, Charles M Ewing, Mario A Eisenberger, Michael A Carducci, William G Nelson, Srinivasan Yegnasubramanian, Jun Luo, Yue Wang, Jianfeng Xu, William B Isaacs, Tapio Visakorpi & G Steven Bova

doi:10.1038/nm.1944

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.

First Paragraph - | Full Text - Copy number analysis indicates monoclonal origin of lethal metastatic prostate cancer | PDF (1,323 KB) - Copy number analysis indicates monoclonal origin of lethal metastatic prostate cancer | Supplementary information

Nanofluidic proteomic assay for serial analysis of oncoprotein activation in clinical specimens - pp566 - 571

Alice C Fan, Debabrita Deb-Basu, Mathias W Orban, Jason R Gotlib, Yasodha Natkunam, Roger O'Neill, Rose-Ann Padua, Liwen Xu, Daryl Taketa, Amy E Shirer, Shelly Beer, Ada X Yee, David W Voehringer & Dean W Felsher

doi:10.1038/nm.1903

Here Fan et al. describe a protein analysis platform for the sensitive, nanoscale diagnosis and investigation of clinical specimens, including monitoring the response to targeted therapeutics. The nanofluidic proteomic immunoassay can be used to quantify total and phosphorylated forms of oncoproteins in small tumor samples and has been validated in vivo in mouse tumors and in clinical specimens from blood, surgical biopsies and fine-needle aspirates.

Abstract - | Full Text - Nanofluidic proteomic assay for serial analysis of oncoprotein activation in clinical specimens | PDF (451 KB) - Nanofluidic proteomic assay for serial analysis of oncoprotein activation in clinical specimens | Supplementary information

The parametric response map is an imaging biomarker for early cancer treatment outcome - pp572 - 576

Craig J Galbán, Thomas L Chenevert, Charles R Meyer, Christina Tsien, Theodore S Lawrence, Daniel A Hamstra, Larry Junck, Pia C Sundgren, Timothy D Johnson, David J Ross, Alnawaz Rehemtulla & Brian D Ross

doi:10.1038/nm.1919

In this study, Galbán and his colleagues describe a voxel-wise approach for the quantification of tumor microvasculature properties from perfusion magnetic resonance imaging data. When compared to the standard method of using region of interest analysis of changes in relative cerebral blood flow and volume, the parametric response map approach was found to be more predictive of treatment outcomes and overall survival in individuals with high-grade glioma.

Abstract - | Full Text - The parametric response map is an imaging biomarker for early cancer treatment outcome | PDF (416 KB) - The parametric response map is an imaging biomarker for early cancer treatment outcome | Supplementary information

Chromosome instability is common in human cleavage-stage embryos - pp577 - 583

Evelyne Vanneste, Thierry Voet, Cédric Le Caignec, Michèle Ampe, Peter Konings, Cindy Melotte, Sophie Debrock, Mustapha Amyere, Miikka Vikkula, Frans Schuit, Jean-Pierre Fryns, Geert Verbeke, Thomas D'Hooghe, Yves Moreau & Joris R Vermeesch

doi:10.1038/nm.1924

Vanneste and her colleagues describe an array-based approach for scoring genome-wide DNA copy number variations and loss of heterozygosity in single cells. They show that chromosome instability patterns, reminiscent of those seen in human cancers, are also common in cleavage-stage in vitro–fertilized embryos. Such findings during early human embryogenesis could provide a basis for the low fecundity and high miscarriage rate in humanspages 490–491..

Abstract - | Full Text - Chromosome instability is common in human cleavage-stage embryos | PDF (631 KB) - Chromosome instability is common in human cleavage-stage embryos | Supplementary information

See also: News and Views by Ledbetter

Corrigendum: Regulation of cardiovascular development and integrity by the heart of glass– cerebral cavernous malformation protein pathway - p584

Benjamin Kleaveland, Xiangjian Zheng, Jian J Liu, Yannick Blum, Jennifer J Tung, Zhiying Zou, Shawn M Sweeney, Mei Chen, Lili Guo, Min-min Lu, Diane Zhou, Jan Kitajewski, Markus Affolter, Mark H Ginsberg & Mark L Kahn

doi:10.1038/nm0509-584a

Full Text - Corrigendum: Regulation of cardiovascular development and integrity by the heart of glass– cerebral cavernous malformation protein pathway | PDF (62 KB) - Corrigendum: Regulation of cardiovascular development and integrity by the heart of glass– cerebral cavernous malformation protein pathway

Corrigendum: A pivotal role for galectin-1 in fetomaternal tolerance - p584

Sandra M Blois, Juan M Ilarregui, Mareike Tometten, Mariana Garcia, Arif S Orsal, Rosalia Cordo-Russo, Marta A Toscano, Germán A Bianco, Peter Kobelt, Bori Handjiski, Irene Tirado, Udo R Markert, Burghard F Klapp, Francoise Poirier, Julia Szekeres-Bartho, Gabriel A Rabinovich & Petra C Arck

doi:10.1038/nm0509-584b

Full Text - Corrigendum: A pivotal role for galectin-1 in fetomaternal tolerance | PDF (62 KB) - Corrigendum: A pivotal role for galectin-1 in fetomaternal tolerance