One size does not fit all - p1291

doi:10.1038/nm1208-1291

The recent proposal from the European Commission (EC) for a new directive on the protection of animals used in research is well intentioned, but some of its ramifications could cause it to backfire.

Abstract - | Full Text - One size does not fit all | PDF (92 KB) - One size does not fit all

Proposed animal research reforms spark concern in Europe - p1293

Daniel Cressey

doi:10.1038/nm1208-1293

Full Text - Proposed animal research reforms spark concern in Europe | PDF (204 KB) - Proposed animal research reforms spark concern in Europe

In tough times, personalized medicine needs specific partners - p1294

Coco Ballantyne

doi:10.1038/nm1208-1294

Full Text - In tough times, personalized medicine needs specific partners | PDF (199 KB) - In tough times, personalized medicine needs specific partners

Preliminary studies find DNA erosion in mental disorders - p1295

David Gruber

doi:10.1038/nm1208-1295a

Full Text - Preliminary studies find DNA erosion in mental disorders | PDF (129 KB) - Preliminary studies find DNA erosion in mental disorders

Helpful bacteria harnessed to fight bad bugs - p1295

Coco Ballantyne

doi:10.1038/nm1208-1295b

Full Text - Helpful bacteria harnessed to fight bad bugs | PDF (129 KB) - Helpful bacteria harnessed to fight bad bugs

News in brief - pp1296 - 1297

doi:10.1038/nm1208-1296

Full Text - News in brief | PDF (666 KB) - News in brief

Straight talk with...Jim Yong Kim - pp1298 - 1299

Prashant Nair

doi:10.1038/nm1208-1298

From his early years as a medical student at Harvard University to his job as the director of the HIV/AIDS unit at the World Health Organization (WHO), Jim Yong Kim has worked toward building health care systems to provide care for poor people on a global scale. In the late 1980s, Kim worked with a team of doctors from the Cambridge, Massachusetts–based nonprofit Partners in Health to upend conventional wisdom on treatment for drug-resistant tuberculosis in the shantytowns of Lima, Peru. The team's campaign brought the price of tuberculosis drugs down about 90%. Kim, a physician who also has a doctorate in medical anthropology, says that the success helped overturn the notion that the disease could not be treated in such a poor setting.

While at the WHO, he turned his attention to AIDS. In 2003, amid much skepticism, his team launched the global '3 by 5' campaign, an ambitious movement aimed at providing antiretroviral drugs to 3 million people worldwide by 2005. Today, Kim leads the François-Xavier Bagnoud Center for Health and Human Rights at the Harvard School of Public Health, where he oversees programs to address health issues plaguing poor childrenóespecially those afflicted with AIDS. Kim discussed the current state of universal AIDS treatment and the role of biomedical research in promoting social justice with Prashant Nair.

Abstract - | Full Text - Straight talk with...Jim Yong Kim | PDF (322 KB) - Straight talk with...Jim Yong Kim

Australian agency proceeds cautiously with Hwang patent - p1300

Simon Grose

doi:10.1038/nm1208-1300a

Full Text - Australian agency proceeds cautiously with Hwang patent | PDF (240 KB) - Australian agency proceeds cautiously with Hwang patent

Biomedical sector takes steps to handle harsh financial realities - p1300

Meredith Wadman

doi:10.1038/nm1208-1300b

Full Text - Biomedical sector takes steps to handle harsh financial realities | PDF (240 KB) - Biomedical sector takes steps to handle harsh financial realities

The road to speed - p1307

Margaret Gnegy reviews On Speed: The Many Lives of Amphetamine by Nicolas Rasmussen

doi:10.1038/nm1208-1307

Full Text - The road to speed | PDF (106 KB) - The road to speed

Brain inflammation initiates seizures - pp1309 - 1310

Jonathan K Kleen & Gregory L Holmes

doi:10.1038/nm1208-1309

Interfering with the adhesion of immune cells to the cerebral vasculature holds seizures in check, potentially opening a new realm of therapeutics (pages 1377–1383).

Abstract - | Full Text - Brain inflammation initiates seizures | PDF (671 KB) - Brain inflammation initiates seizures

See also: Letter by Fabene et al.

Saving the skin from drug-induced detachment - pp1311 - 1313

Brian J Nickoloff

doi:10.1038/nm1208-1311

Granulysin, a powerful cytolytic protein secreted from immune cells, underlies an extreme and deadly response to common medications, in which the skin blisters and sloughs off. The findings may also have implications for bone marrow transplant recipients suffering from graft-versus-host disease (pages 1343–1350).

Abstract - | Full Text - Saving the skin from drug-induced detachment | PDF (1,221 KB) - Saving the skin from drug-induced detachment

See also: Letter by Chung et al.

Breaking the pain connection - pp1313 - 1315

Catherine J Pallen

doi:10.1038/nm1208-1313

A small peptide eases pain in several types of mouse models. The peptide targets a protein interaction within a pain-mediating complex—containing the N-methyl-D-aspartate receptor—without affecting normal physiological processes (pages 1325–1332).

Abstract - | Full Text - Breaking the pain connection | PDF (771 KB) - Breaking the pain connection

See also: Article by Liu et al.

Targeting RAS and PI3K in lung cancer - pp1315 - 1316

Julian Downward

doi:10.1038/nm1208-1315

The phosphoinositide 3-kinase (PI3K) and RAS oncoproteins are activated in many major tumor types and control linked signaling pathways. An inhibitor of PI3K is now shown to shrink tumors in transgenic mouse cancer models. The drug also blocks RAS-induced lung tumors when combined with an inhibitor of mitogen-activated protein kinase kinase (pages 1351–1356).

Abstract - | Full Text - Targeting RAS and PI3K in lung cancer | PDF (446 KB) - Targeting RAS and PI3K in lung cancer

See also: Letter by Engelman et al.

Building a prostate - p1317

doi:10.1038/nm1208-1317

Full Text - Building a prostate | PDF (214 KB) - Building a prostate

Toll-free immunity? - pp1318 - 1319

Nicholas Valiante, Ennio De Gregorio & Rino Rappuoli

doi:10.1038/nm1208-1318

Toll-like receptors (TLRs), molecules that recognize molecular components of microbes, have taken center stage in immunologists' view of how innate immunity is triggered. A study in people genetically deficient for MyD88, a molecule central to TLR signaling in mice, should now spur a reexamination of simple views of TLR biology, as Rino Rappuoli and his colleagues explain. Delphine J. Lee and Robert L. Modlin examine how TLR9 recognition of self DNA, instead of microbe DNA, may prompt autoimmunity.

Abstract - | Full Text - Toll-free immunity? | PDF (296 KB) - Toll-free immunity?

DNA transportation authority - pp1319 - 1320

Delphine J Lee & Robert L Modlin

doi:10.1038/nm1208-1319

Full Text - DNA transportation authority | PDF (970 KB) - DNA transportation authority

Research Highlights - pp1322 - 1323

doi:10.1038/nm1208-1322

Full Text - Research Highlights | PDF (209 KB) - Research Highlights

Treatment of inflammatory and neuropathic pain by uncoupling Src from the NMDA receptor complex - pp1325 - 1332

Xue Jun Liu, Jeffrey R Gingrich, Mariana Vargas-Caballero, Yi Na Dong, Ameet Sengar, Simon Beggs, Szu-Han Wang, Hoi Ki Ding, Paul W Frankland & Michael W Salter

doi:10.1038/nm.1883

Glutamate NMDA receptors are involved in pain signaling, but inhibiting them would have too many side effects. These authors show that inhibiting the binding of NMDA receptors to Src, a molecule that is resposible for amplifying glutamate signaling, reduces inflammatory and neuropathic pain in mice and rats (pages 1313–1315).

Abstract - | Full Text - Treatment of inflammatory and neuropathic pain by uncoupling Src from the NMDA receptor complex | PDF (499 KB) - Treatment of inflammatory and neuropathic pain by uncoupling Src from the NMDA receptor complex | Supplementary information

See also: News and Views by Pallen

Eradication of acute promyelocytic leukemia-initiating cells through PML-RARA degradation - pp1333 - 1342

Rihab Nasr, Marie-Claude Guillemin, Omar Ferhi, Hassan Soilihi, Laurent Peres, Caroline Berthier, Philippe Rousselot, Macarena Robledo-Sarmiento, Valérie Lallemand-Breitenbach, Bernard Gourmel, Dominique Vitoux, Pier Paolo Pandolfi, Cécile Rochette-Egly, Jun Zhu & Hugues de Thé

doi:10.1038/nm.1891

Retinoic acid and arsenic induce the differentiation of acute promyelocytic leukemia (APL) cells and clinical responses in individuals with APL. Nasr and colleagues now show that by triggering the degradation of the PML-RARA oncogenic fusion protein retinoic acid and arsenic also deplete the leukemia initiating cells, accounting for disease remission in a mouse model of APL.

Abstract - | Full Text - Eradication of acute promyelocytic leukemia-initiating cells through PML-RARA degradation | PDF (1,033 KB) - Eradication of acute promyelocytic leukemia-initiating cells through PML-RARA degradation | Supplementary information

Granulysin is a key mediator for disseminated keratinocyte death in Stevens-Johnson syndrome and toxic epidermal necrolysis - pp1343 - 1350

Wen-Hung Chung, Shuen-Iu Hung, Jui-Yung Yang, Shih-Chi Su, Shien-Ping Huang, Chun-Yu Wei, See-Wen Chin, Chien-Chun Chiou, Sung-Chao Chu, Hsin-Chun Ho, Chih-Hsun Yang, Chi-Fang Lu, Jer-Yuarn Wu, You-Di Liao & Yuan-Tsong Chen

doi:10.1038/nm.1884

Drug hypersensitivity reactions can result in life-threatening epidermal necrosis caused by cytotoxic T lymphocytes and natural killer cells. Chung et al. show that an unusual form of granulysin secreted from these cells is largely responsible for the cell death (pages 1311–1313).

First Paragraph - | Full Text - Granulysin is a key mediator for disseminated keratinocyte death in Stevens-Johnson syndrome and toxic epidermal necrolysis | PDF (615 KB) - Granulysin is a key mediator for disseminated keratinocyte death in Stevens-Johnson syndrome and toxic epidermal necrolysis | Supplementary information

See also: News and Views by Nickoloff

Effective use of PI3K and MEK inhibitors to treat mutant Kras G12D and PIK3CA H1047R murine lung cancers - pp1351 - 1356

Jeffrey A Engelman, Liang Chen, Xiaohong Tan, Katherine Crosby, Alexander R Guimaraes, Rabi Upadhyay, Michel Maira, Kate McNamara, Samanthi A Perera, Youngchul Song, Lucian R Chirieac, Ramneet Kaur, Angela Lightbown, Jessica Simendinger, Timothy Li, Robert F Padera, Carlos García-Echeverría, Ralph Weissleder, Umar Mahmood, Lewis C Cantley & Kwok-Kin Wong

doi:10.1038/nm.1890

Inhibitors of PI3 kinase are in development for the treatment of cancer. But whether these compounds will work as single agents remains to be seen. Engelman et al. now show that a PI3K-mTOR inhibitor is effective in a mouse model of lung cancer induced by a mutant PIK3CA but has no effect on Kras-induced tumors. Combining the PI3K-mTOR inhibitor with a MEK inhibitor induced regression of mouse Kras tumors, suggesting that such combinations may be beneficial in human tumors (pages 1315–1316).

First Paragraph - | Full Text - Effective use of PI3K and MEK inhibitors to treat mutant Kras G12D and PIK3CA H1047R murine lung cancers | PDF (842 KB) - Effective use of PI3K and MEK inhibitors to treat mutant Kras G12D and PIK3CA H1047R murine lung cancers | Supplementary information

See also: News and Views by Downward

Targeting inside-out phosphatidylserine as a therapeutic strategy for viral diseases - pp1357 - 1362

M Melina Soares, Steven W King & Philip E Thorpe

doi:10.1038/nm.1885

When viruses infect cells, they trigger changes such as exposure of phosphatidylserine on the cell surface. Thorpe et al. have shown that this 'inside-out' phosphatidylserine can be targeted by an antibody, and this approach can clear virus infection in mice.

First Paragraph - | Full Text - Targeting inside-out phosphatidylserine as a therapeutic strategy for viral diseases | PDF (366 KB) - Targeting inside-out phosphatidylserine as a therapeutic strategy for viral diseases | Supplementary information

BMP type I receptor inhibition reduces heterotopic ossification - pp1363 - 1369

Paul B Yu, Donna Y Deng, Carol S Lai, Charles C Hong, Gregory D Cuny, Mary L Bouxsein, Deborah W Hong, Patrick M McManus, Takenobu Katagiri, Chetana Sachidanandan, Nobuhiro Kamiya, Tomokazu Fukuda, Yuji Mishina, Randall T Peterson & Kenneth D Bloch

doi:10.1038/nm.1888

Ectopic ossification often involves the transformation of soft tissue into bone. In this new study, Paul Yu et al. show that inflammation is a key step in disease progression and that a small molecule inhibitor of the disease gene's protein product is therapeutic, thus offering a potential treatment for this devastating condition.

First Paragraph - | Full Text - BMP type I receptor inhibition reduces heterotopic ossification | PDF (915 KB) - BMP type I receptor inhibition reduces heterotopic ossification | Supplementary information

Modification of mineralocorticoid receptor function by Rac1 GTPase: implication in proteinuric kidney disease - pp1370 - 1376

Shigeru Shibata, Miki Nagase, Shigetaka Yoshida, Wakako Kawarazaki, Hidetake Kurihara, Hirotoshi Tanaka, Jun Miyoshi, Yoshimi Takai & Toshiro Fujita

doi:10.1038/nm.1879

Inhibition of mineralcorticoid receptor activity is known to improve the outcome of chronic kidney disease. In this new report, Toshiro Fujita and his colleagues show that Rac1 strongly potentiates mineralcorticoid receptor signaling by enhancing its nuclear localization and that Rac1 inhibition is ameliorative in two rodent models of renal disease.

First Paragraph - | Full Text - Modification of mineralocorticoid receptor function by Rac1 GTPase: implication in proteinuric kidney disease | PDF (730 KB) - Modification of mineralocorticoid receptor function by Rac1 GTPase: implication in proteinuric kidney disease | Supplementary information

A role for leukocyte-endothelial adhesion mechanisms in epilepsy - pp1377 - 1383

Paolo F Fabene, Graciela Navarro Mora, Marianna Martinello, Barbara Rossi, Flavia Merigo, Linda Ottoboni, Simona Bach, Stefano Angiari, Donatella Benati, Asmaa Chakir, Lara Zanetti, Federica Schio, Antonio Osculati, Pasquina Marzola, Elena Nicolato, Jonathon W Homeister, Lijun Xia, John B Lowe, Rodger P McEver, Francesco Osculati, Andrea Sbarbati, Eugene C Butcher & Gabriela Constantin

doi:10.1038/nm.1878

The authors examine how brain inflammation affects the development of epilepsy. They show that genetic or antibody-mediated blockade of leukocyte-vascular interactions reduces epileptogenesis in mice (pages 1309–1310).

First Paragraph - | Full Text - A role for leukocyte-endothelial adhesion mechanisms in epilepsy | PDF (654 KB) - A role for leukocyte-endothelial adhesion mechanisms in epilepsy | Supplementary information

See also: News and Views by Kleen & Holmes

A method for quantifying normal human mammary epithelial stem cells with in vivo regenerative ability - pp1384 - 1389

Peter Eirew, John Stingl, Afshin Raouf, Gulisa Turashvili, Samuel Aparicio, Joanne T Emerman & Connie J Eaves

doi:10.1038/nm.1791

Peter Eirew and his colleagues describe a new assay for detecting, quantifying and characterizing normal human mammary epithelial stem cells. The assay, which combines in vivo transplantation under the kidney capsule of immunodeficient mice and an in vitro colony-forming assay, provides a system for studying the mechanisms regulating normal human mammary stem cell proliferation and differentiation in vivo and in human breast cancer.

Abstract - | Full Text - A method for quantifying normal human mammary epithelial stem cells with in vivo regenerative ability | PDF (407 KB) - A method for quantifying normal human mammary epithelial stem cells with in vivo regenerative ability | Supplementary information

Control of HIV-1 immune escape by CD8 T cells expressing enhanced T-cell receptor - pp1390 - 1395

Angel Varela-Rohena, Peter E Molloy, Steven M Dunn, Yi Li, Megan M Suhoski, Richard G Carroll, Anita Milicic, Tara Mahon, Deborah H Sutton, Bruno Laugel, Ruth Moysey, Brian J Cameron, Annelise Vuidepot, Marco A Purbhoo, David K Cole, Rodney E Phillips, Carl H June, Bent K Jakobsen, Andrew K Sewell & James L Riley

doi:10.1038/nm.1779

In HIV research, new types of reagents are needed to target infected cells and overcome HIV's ability to vary its HLA-I-restricted antigens and escape from host cytotoxic T lymphocytes. Here Varela-Rohena and colleagues use phage display technology to generate high-affinity T-cell antigen receptors that recognize common epitope-escape variants of the immunodominant HLA-A^*02-restricted, HIVgag-specific peptide SLYNTVATL (SL9).

Abstract - | Full Text - Control of HIV-1 immune escape by CD8 T cells expressing enhanced T-cell receptor | PDF (463 KB) - Control of HIV-1 immune escape by CD8 T cells expressing enhanced T-cell receptor | Supplementary information