Risky business - p345

doi:10.1038/nm0409-345

A recent US Supreme Court ruling places responsibility for the wording of drug labels on pharmaceutical companies. But the task of improving the communication of drug risks does not rest with the pharmaceutical industry alone.

Abstract - | Full Text - Risky business | PDF (106 KB) - Risky business

A stem cell ban is lifted, but some states see a heavy backlash - p347

Kirsten Dorans

doi:10.1038/nm0409-347

Full Text - A stem cell ban is lifted, but some states see a heavy backlash | PDF (198 KB) - A stem cell ban is lifted, but some states see a heavy backlash

Five big ideas for nanotechnology - p348

Jon Evans

doi:10.1038/nm0409-348

Full Text - Five big ideas for nanotechnology | PDF (265 KB) - Five big ideas for nanotechnology

Biosafety bungle leads to bird flu contamination - p349

Cassandra Willyard

doi:10.1038/nm0409-349a

Full Text - Biosafety bungle leads to bird flu contamination | PDF (147 KB) - Biosafety bungle leads to bird flu contamination

Blueprint for autism research put forward - p349

Virginia Hughes

doi:10.1038/nm0409-349b

Full Text - Blueprint for autism research put forward | PDF (147 KB) - Blueprint for autism research put forward

US stimulus bill challenges biomedicine to deliver - p350

Kirsten Dorans

doi:10.1038/nm0409-350a

Full Text - US stimulus bill challenges biomedicine to deliver | PDF (124 KB) - US stimulus bill challenges biomedicine to deliver

New cancer research centers open in UK - p350

Nayanah Siva

doi:10.1038/nm0409-350b

Full Text - New cancer research centers open in UK | PDF (124 KB) - New cancer research centers open in UK

Dutch seizure of drugs sparks outcry - p350

Nayanah Siva

doi:10.1038/nm0409-350c

Full Text - Dutch seizure of drugs sparks outcry | PDF (124 KB) - Dutch seizure of drugs sparks outcry

A vaccine based on conserved regions could prove radical - p351

Kirsten Dorans

doi:10.1038/nm0409-351a

Full Text - A vaccine based on conserved regions could prove radical | PDF (183 KB) - A vaccine based on conserved regions could prove radical

Broad-acting HPV vaccines explored to fight cancer - p351

Kirsten Dorans

doi:10.1038/nm0409-351b

Full Text - Broad-acting HPV vaccines explored to fight cancer | PDF (183 KB) - Broad-acting HPV vaccines explored to fight cancer

News in brief - pp352 - 353

doi:10.1038/nm0409-352

Full Text - News in brief | PDF (620 KB) - News in brief

Straight talk with ... Agnès Saint Raymond - pp354 - 355

Genevive Bjorn

doi:10.1038/nm0409-354

Agnès Saint Raymond has long advocated for children's health and worked with members of the European Parliament to draft and pass new legislation in 2006 to promote drug development in this area. She spoke with Genevive Bjorn about the future of medicines designed for youngsters.

Abstract - | Full Text - Straight talk with ... Agnès Saint Raymond | PDF (463 KB) - Straight talk with ... Agnès Saint Raymond

The curious case of clioquinol - pp356 - 359

Lauren Cahoon

doi:10.1038/nm0409-356

An indigestion drug blamed for a debilitating illness that affected thousands of people in the 1950s has been resurrected as a potential treatment for Alzheimer's disease. But not everyone is cheering for the drug, clioquinol, to make a comeback. Lauren Cahoon reports.

Abstract - | Full Text - The curious case of clioquinol | PDF (1,038 KB) - The curious case of clioquinol

A new progressive era? - p361

Scott H Podolsky reviews Our Daily Meds: How the Pharmaceutical Companies Transformed Themselves into Slick Marketing Machines and Hooked the Nation on Prescription Drugs by Melody Petersen

doi:10.1038/nm0409-361

Full Text - A new progressive era? | PDF (109 KB) - A new progressive era?

Choosing between GVHD and delayed engraftment - pp363 - 364

Paul J Martin

doi:10.1038/nm0409-363

Growth factors used to accelerate engraftment after hematopoietic cell transplantation can increase the severity of graft-versus-host disease. Experiments with mice examine how irradiation, used to prepare recipients for transplants, contributes to this problem (pages 436–441).

Abstract - | Full Text - Choosing between GVHD and delayed engraftment | PDF (424 KB) - Choosing between GVHD and delayed engraftment

See also: Letter by Morris et al.

Neutrophil sandwiches injure the microcirculation - pp364 - 366

Mark R Looney & Michael A Matthay

doi:10.1038/nm0409-364

Experiments in two mouse models of thromboinflammatory disease show how neutrophils stick to red blood cells and platelets—leading to reduced blood flow and damage to the microcirculation. Polarized expression of _M2 integrins on neutrophils helps set the process in motion (pages 384–391).

Abstract - | Full Text - Neutrophil sandwiches injure the microcirculation | PDF (2,861 KB) - Neutrophil sandwiches injure the microcirculation

See also: Article by Hidalgo et al.

Dust mites' dirty dealings in the lung - pp366 - 367

Clare M Lloyd

doi:10.1038/nm0409-366

Toll-like receptors on lung epithelia recognize allergens and help provoke asthma. The findings put new emphasis on innate immunity as a driver of allergic responses (pages 410–416).

Abstract - | Full Text - Dust mites' dirty dealings in the lung | PDF (841 KB) - Dust mites' dirty dealings in the lung

See also: Article by Hammad et al.

Neuropeptide beckons cells that heal - pp367 - 369

Pamela Gehron Robey

doi:10.1038/nm0409-367

Experiments in rodents identify a factor that causes the release of multipotent cells into the circulation after injury. These cells contribute to tissue repair (pages 425–435).

Abstract - | Full Text - Neuropeptide beckons cells that heal | PDF (708 KB) - Neuropeptide beckons cells that heal

See also: Article by Hong et al.

Bone marrow transplant muffles HIV - p371

doi:10.1038/nm0409-371

Full Text - Bone marrow transplant muffles HIV | PDF (132 KB) - Bone marrow transplant muffles HIV

Getting away from glucose: stop sugarcoating diabetes - pp372 - 373

Babak Razani & Clay F Semenkovich

doi:10.1038/nm0409-372

Type 2 diabetes is often viewed as a disorder of glucose metabolism. But many factors come into play in this condition, with obesity a prime risk factor and cardiovascular disease a major result. In Bedside to Bench, Babak Razani and Clay Semenkovich examine the linkages between diabetes and cardiovascular disease. They call for new research approaches in the wake of clinical trials showing that lowering glucose levels does not decrease cardiovascular events in people with type 2 diabetes. In Bench to Bedside, Steven Shoelson and Allison Goldfine examine how type 2 diabetes and other disorders can stem from obesity—and its effect on inflammation. These authors take a look at two recent studies showing how obesity perturbs inflammatory gene networks.

Abstract - | Full Text - Getting away from glucose: stop sugarcoating diabetes | PDF (234 KB) - Getting away from glucose: stop sugarcoating diabetes

Getting away from glucose: fanning the flames of obesity-induced inflammation - pp373 - 374

Steven E Shoelson & Allison B Goldfine

doi:10.1038/nm0409-373

Full Text - Getting away from glucose: fanning the flames of obesity-induced inflammation | PDF (98 KB) - Getting away from glucose: fanning the flames of obesity-induced inflammation

Research Highlights - p375

doi:10.1038/nm0409-375

Full Text - Research Highlights | PDF (168 KB) - Research Highlights

Amyloid precursor protein secretases as therapeutic targets for traumatic brain injury - pp377 - 379

David J Loane, Ana Pocivavsek, Charbel E-H Moussa, Rachel Thompson, Yasuji Matsuoka, Alan I Faden, G William Rebeck & Mark P Burns

doi:10.1038/nm.1940

The neurotoxic A peptide is produced after traumatic brain injury. Mark P. Burns and his colleagues show that inhibiting the enzymes involved in A production can block the neuron death and neurological dysfunction that occurs after traumatic brain injury.

Abstract - | Full Text - Amyloid precursor protein secretases as therapeutic targets for traumatic brain injury | PDF (362 KB) - Amyloid precursor protein secretases as therapeutic targets for traumatic brain injury | Supplementary information

Flecainide prevents catecholaminergic polymorphic ventricular tachycardia in mice and humans - pp380 - 383

Hiroshi Watanabe, Nagesh Chopra, Derek Laver, Hyun Seok Hwang, Sean S Davies, Daniel E Roach, Henry J Duff, Dan M Roden, Arthur A M Wilde & Björn C Knollmann

doi:10.1038/nm.1942

Catecholaminergic polymorphic ventricular tachycardia (CPVT) is an inherited arrhythmia syndrome that is often difficult to treat. Hiroshi Watanabe and coworkers now show that flecainide, an approved drug known to inhibit sodium channels, is able to target the underlying cause of CPVT by inhibiting calcium release through the ryanodine receptor. Flecainide prevented arrhythmia in a mouse model of CPVT and was also effective when tested in two individuals with CPVT.

Abstract - | Full Text - Flecainide prevents catecholaminergic polymorphic ventricular tachycardia in mice and humans | PDF (397 KB) - Flecainide prevents catecholaminergic polymorphic ventricular tachycardia in mice and humans | Supplementary information

Heterotypic interactions enabled by polarized neutrophil microdomains mediate thromboinflammatory injury - pp384 - 391

Andrés Hidalgo, Jungshan Chang, Jung-Eun Jang, Anna J Peired, Elaine Y Chiang & Paul S Frenette

doi:10.1038/nm.1939

Signaling between endothelial and blood cell types controls inflammatory and thrombotic responses. Andrés Hidalgo and his coworkers now uncover a signaling mechanism by which the endothelium, acting on adherent leukocytes, promotes the capture of platelets or red blood cells by those leukocytes, contributing to pathology in mouse models of two very different types of disease—transfusion-related acute lung injury and sickle cell disease(pages 364–366).

Abstract - | Full Text - Heterotypic interactions enabled by polarized neutrophil microdomains mediate thromboinflammatory injury | PDF (485 KB) - Heterotypic interactions enabled by polarized neutrophil microdomains mediate thromboinflammatory injury | Supplementary information

See also: News and Views by Looney & Matthay

Stimulation of tumor growth and angiogenesis by low concentrations of RGD-mimetic integrin inhibitors - pp392 - 400

Andrew R Reynolds, Ian R Hart, Alan R Watson, Jonathan C Welti, Rita G Silva, Stephen D Robinson, Georges Da Violante, Morgane Gourlaouen, Mishal Salih, Matt C Jones, Dylan T Jones, Garry Saunders, Vassiliki Kostourou, Françoise Perron-Sierra, Jim C Norman, Gordon C Tucker & Kairbaan M Hodivala-Dilke

doi:10.1038/nm.1941

Inhibitors of _v3 and _v5 integrins have previously been shown to inhibit tumor angiogenesis and growth and have entered human clinical trials. Andrew Reynolds and his coworkers now show that low (nanomolar) concentrations of these inhibitors can unexpectedly promote VEGF-dependent tumor angiogenesis and growth in vivo. Such effects could compromise the anticancer efficacy of these agents in humans.

Abstract - | Full Text - Stimulation of tumor growth and angiogenesis by low concentrations of RGD-mimetic integrin inhibitors | PDF (656 KB) - Stimulation of tumor growth and angiogenesis by low concentrations of RGD-mimetic integrin inhibitors | Supplementary information

Toll-like receptor 2–dependent induction of vitamin A–metabolizing enzymes in dendritic cells promotes T regulatory responses and inhibits autoimmunity - pp401 - 409

Santhakumar Manicassamy, Rajesh Ravindran, Jiusheng Deng, Herold Oluoch, Timothy L Denning, Sudhir Pai Kasturi, Kristen M Rosenthal, Brian D Evavold & Bali Pulendran

doi:10.1038/nm.1925

Bali Pulendran and his colleagues explore ways that signaling through different pathogen receptors can program dendritic cells (DCs) to orchestrate inflammatory or tolerogenic immune responses. The yeast component zymosan triggers signaling through both Toll-like receptor 2 (TLR2) and the C-type lectin dectin-1. In the absence of TLR2, zymosan induces proinflammatory responses through dectin-1. But TLR2 triggering induces DCs to form the vitamin A–metabolizing enzyme Raldh2. The DCs can then form retinoic acid that acts in an autocrine manner on the DCs, programming them for the induction of regulatory T cell responses.

Abstract - | Full Text - Toll-like receptor 2–dependent induction of vitamin A–metabolizing enzymes in dendritic cells promotes T regulatory responses and inhibits autoimmunity | PDF (723 KB) - Toll-like receptor 2–dependent induction of vitamin A–metabolizing enzymes in dendritic cells promotes T regulatory responses and inhibits autoimmunity | Supplementary information

House dust mite allergen induces asthma via Toll-like receptor 4 triggering of airway structural cells - pp410 - 416

Hamida Hammad, Marcello Chieppa, Frederic Perros, Monique A Willart, Ronald N Germain & Bart N Lambrecht

doi:10.1038/nm.1946

House dust mite allergen (HDM) is a potent trigger of airway inflammation. Dendritic cells (DCs) and lung epithelial cells both express the pathogen receptor TLR4, which senses lipopolysaccharide contaminating the allergen. Bart Lambrecht and his colleagues show that TLR4 on the epithelial cells, not the DCs, is the primary sensor of HDM. TLR4 on these lung structural cells is required for recruitment of DCs and the induction of allergic inflammation in response to HDM (pages 366–367).

Abstract - | Full Text - House dust mite allergen induces asthma via Toll-like receptor 4 triggering of airway structural cells | PDF (511 KB) - House dust mite allergen induces asthma via Toll-like receptor 4 triggering of airway structural cells | Supplementary information

See also: News and Views by Lloyd

Estrogen-dependent and C-C chemokine receptor-2–dependent pathways determine osteoclast behavior in osteoporosis - pp417 - 424

Nikolaus B Binder, Birgit Niederreiter, Oskar Hoffmann, Richard Stange, Thomas Pap, Thomas M Stulnig, Matthias Mack, Reinhold G Erben, Josef S Smolen & Kurt Redlich

doi:10.1038/nm.1945

Kurt Redlich and his colleagues show that estrogen deficiency results in increased numbers of preosteoclast progenitor cells in the bones of mice. But they also find that lack of CCR2 in these future bone-resorbing cells prevents their maturation and thus protects the mice from osteoporosis, suggesting a future target for therapy in humans.

Abstract - | Full Text - Estrogen-dependent and C-C chemokine receptor-2–dependent pathways determine osteoclast behavior in osteoporosis | PDF (647 KB) - Estrogen-dependent and C-C chemokine receptor-2–dependent pathways determine osteoclast behavior in osteoporosis | Supplementary information

A new role of substance P as an injury-inducible messenger for mobilization of CD29⁺ stromal-like cells - pp425 - 435

Hyun Sook Hong, Jungsun Lee, EunAh Lee, Young Sam Kwon, Eunkyung Lee, Woosung Ahn, Mei Hua Jiang, Jae Chan Kim & Youngsook Son

doi:10.1038/nm.1909

New factors in wound healing are sorely needed. Here Youngsook Son and colleagues identify substance P, a small neuropeptide, as one such factor that seems to work by mobilizing stromal-like cells to the site of wounding, accelerating the healing process (pages 367–369).

Abstract - | Full Text - A new role of substance P as an injury-inducible messenger for mobilization of CD29+ stromal-like cells | PDF (1,086 KB) - A new role of substance P as an injury-inducible messenger for mobilization of CD29+ stromal-like cells | Supplementary information

See also: News and Views by Robey

Induction of natural killer T cell–dependent alloreactivity by administration of granulocyte colony–stimulating factor after bone marrow transplantation - pp436 - 441

Edward S Morris, Kelli P A MacDonald, Rachel D Kuns, Helen M Morris, Tatjana Banovic, Alistair L J Don, Vanessa Rowe, Yana A Wilson, Neil C Raffelt, Christian R Engwerda, Angela C Burman, Kate A Markey, Dale I Godfrey, Mark J Smyth & Geoffrey R Hill

doi:10.1038/nm.1948

Granulocyte colony-stimulating factor (G-CSF) is used to accelerate neutrophil engraftment in bone marrow transplant (BMT) recipients to reduce bacterial infections but may also enhance the risk of graft-versus-host disease (GVHD). Morris et al. now show that total body irradiation increases the expression of the G-CSF receptor on recipient dendritic cells, resulting in the activation of donor natural killer T cells and enhanced GVHD when G-CSF is administered shortly after BMT (pages 363–364).

First Paragraph - | Full Text - Induction of natural killer T cell–dependent alloreactivity by administration of granulocyte colony–stimulating factor after bone marrow transplantation | PDF (457 KB) - Induction of natural killer T cell–dependent alloreactivity by administration of granulocyte colony–stimulating factor after bone marrow transplantation | Supplementary information

See also: News and Views by Martin

Deficiency of the intestinal enzyme acyl CoA:monoacylglycerol acyltransferase-2 protects mice from metabolic disorders induced by high-fat feeding - pp442 - 446

Chi-Liang Eric Yen, Mei-Leng Cheong, Carrie Grueter, Ping Zhou, Junya Moriwaki, Jinny S Wong, Brian Hubbard, Stephen Marmor & Robert V Farese Jr

doi:10.1038/nm.1937

One way to reduce obesity is to alter fat absorption from the diet. Here Robert Farese, Jr. and his colleagues identify MGAT2 as a potential therapeutic target for doing so. The enzyme is mostly expressed in the gut of humans and mice, and its genetic deletion in mice results in slower kinetics of fat absorption—more of the fat is burned and less is stored, offering protection from diet-induced obesity.

First Paragraph - | Full Text - Deficiency of the intestinal enzyme acyl CoA:monoacylglycerol acyltransferase-2 protects mice from metabolic disorders induced by high-fat feeding | PDF (348 KB) - Deficiency of the intestinal enzyme acyl CoA:monoacylglycerol acyltransferase-2 protects mice from metabolic disorders induced by high-fat feeding | Supplementary information

Molecular therapy of obesity and diabetes by a physiological autoregulatory approach - pp447 - 454

Lei Cao, En-Ju D Lin, Michael C Cahill, Chuansong Wang, Xianglan Liu & Matthew J During

doi:10.1038/nm.1933

Viral-mediated gene therapy presents many challenges in the clinic, including the potential for physiological effects that overshoot the intended goals. In a new report by Matthew During and his colleagues, the authors devise a scheme by which packaging of a microRNA into the virus, expressed under the control of a physiological response induced by the viral transgene, allows coordinated dampening of the transgene expression when the therapeutic response achieves a certain threshold.

First Paragraph - | Full Text - Molecular therapy of obesity and diabetes by a physiological autoregulatory approach | PDF (524 KB) - Molecular therapy of obesity and diabetes by a physiological autoregulatory approach | Supplementary information

Bioluminescence imaging of myeloperoxidase activity in vivo - pp455 - 461

Shimon Gross, Seth T Gammon, Britney L Moss, Daniel Rauch, John Harding, Jay W Heinecke, Lee Ratner & David Piwnica-Worms

doi:10.1038/nm.1886

The leukocyte enzyme myeloperoxidase (MPO) is key to normal host defense mechanisms. Dysregulated MPO, however, is linked to acute and chronic inflammatory conditions, such as atherosclerosis and cancer. The authors describe a luminol-based bioluminescence imaging system that provides an optical readout of physiological levels of MPO activity in vivo. The system is demonstrated in animal models of acute dermatitis, focal arthritis and spontaneous large granular lymphocytic tumors.

Abstract - | Full Text - Bioluminescence imaging of myeloperoxidase activity in vivo | PDF (648 KB) - Bioluminescence imaging of myeloperoxidase activity in vivo | Supplementary information

Corrigendum: VEGF modulates erythropoiesis through regulation of adult hepatic erythropoietin synthesis - p462

Betty YFY Tam, Kevin Wei, John S Rudge, Jana Hoffman, Joceyln Holash, Sang-ki Park, Jenny Yuan, Colleen Hefner, Cecile Chartier, Jeng-Shin Lee, Shelly Jiang, Nihar R Nayak, Frans A Kuypers, Lisa Ma, Uma Sundram, Grace Wu, Joseph A Garcia, Stanley L Schrier, Jacquelyn J Maher, Randall S Johnson, George D Yancopoulos, Richard C Mulligan & Calvin J Kuo

doi:10.1038/nm0409-462a

Full Text - Corrigendum: VEGF modulates erythropoiesis through regulation of adult hepatic erythropoietin synthesis | PDF (77 KB) - Corrigendum: VEGF modulates erythropoiesis through regulation of adult hepatic erythropoietin synthesis

Corrigendum: Bone marrow stromal cells attenuate sepsis via prostaglandin E₂–dependent reprogramming of host macrophages to increase their interleukin-10 production - p462

Krisztián Németh, Asada Leelahavanichkul, Peter S T Yuen, Balázs Mayer, Alissa Parmelee, Kent Doi, Pamela G Robey, Kantima Leelahavanichkul, Beverly H Koller, Jared M Brown, Xuzhen Hu, Ivett Jelinek, Robert A Star & Éva Mezey

doi:10.1038/nm0409-462b

Full Text - Corrigendum: Bone marrow stromal cells attenuate sepsis via prostaglandin E2–dependent reprogramming of host macrophages to increase their interleukin-10 production | PDF (77 KB) - Corrigendum: Bone marrow stromal cells attenuate sepsis via prostaglandin E2–dependent reprogramming of host macrophages to increase their interleukin-10 production

Corrigendum: The cerebral cavernous malformation signaling pathway promotes vascular integrity via Rho GTPases - p462

Kevin J Whitehead, Aubrey C Chan, Sutip Navankasattusas, Wonshill Koh, Nyall R London, Jing Ling, Anne H Mayo, Stavros G Drakos, Christopher A Jones, Weiquan Zhu, Douglas A Marchuk, George E Davis & Dean Y Li

doi:10.1038/nm0409-462c

Full Text - Corrigendum: The cerebral cavernous malformation signaling pathway promotes vascular integrity via Rho GTPases | PDF (87 KB) - Corrigendum: The cerebral cavernous malformation signaling pathway promotes vascular integrity via Rho GTPases

Corrigendum: Effector memory T cell responses are associated with protection of rhesus monkeys from mucosal simian immunodeficiency virus challenge. - p462

Scott G Hansen, Cassandra Vieville, Nathan Whizin, Lia Coyne-Johnson, Don C Siess, Derek D Drummond, Alfred W Legasse, Michael K Axthelm, Kelli Oswald, Charles M Trubey, Michael Piatak Jr, Jeffrey D Lifson, Jay A Nelson, Michael A Jarvis & Louis J Picker

doi:10.1038/nm0409-462d

Full Text - Corrigendum: Effector memory T cell responses are associated with protection of rhesus monkeys from mucosal simian immunodeficiency virus challenge. | PDF (87 KB) - Corrigendum: Effector memory T cell responses are associated with protection of rhesus monkeys from mucosal simian immunodeficiency virus challenge.

Erratum: Straight talk with...Mac Cowell and Jason Bobe - p462

Prashant Nair

doi:10.1038/nm0409-462e

Full Text - Erratum: Straight talk with...Mac Cowell and Jason Bobe | PDF (87 KB) - Erratum: Straight talk with...Mac Cowell and Jason Bobe