Rescuing a failing heart: think globally, treat locally

Nature Medicine 15, 25 (2009). doi:10.1038/nm0109-25

Authors: Mark E Anderson & Peter J Mohler

Report details scientific self-censoring

Nature Medicine 15, 5 (2009). doi:10.1038/nm0109-5b

Author: Genevive Bjorn

Religious leaders weigh in on current and future embryo research

Nature Medicine 15, 4 (2009). doi:10.1038/nm0109-4a

Author: Jon Evans

A chemical physicist in biology

Nature Medicine 15, 15 (2009). doi:10.1038/nm0109-15

Author: Judith Goodstein

HPV researchers set sights on preventing skin cancers

Nature Medicine 15, 5 (2009). doi:10.1038/nm0109-5a

Author: Simon Grose

γ-secretase inhibitors: Notch so bad

Nature Medicine 15, 20 (2009). doi:10.1038/nm0109-20

Author: Gerard C Grosveld

γ-secretase inhibitors inhibit Notch, a transmembrane receptor that drives many cases of T cell acute lymphoblastic leukemia—but there are safety concerns with such drugs. Combining these inhibitors with glucocorticoids could provide a more effective and safer approach (pages 50–58).

Challenges anticipated in removal of stem cell restrictions

Nature Medicine 15, 3 (2009). doi:10.1038/nm0109-3

Author: Stu Hutson

Rescuing a failing heart: putting on the squeeze

Nature Medicine 15, 24 (2009). doi:10.1038/nm0109-24

Author: David A Kass

Numerous drugs have been invented to counteract heart failure, but some have not lived up to their initial promise. As David Kass explains, the development of drugs to increase cardiac contractility has been particularly frustrating—but failure is also leading to new biological insights and new experimental approaches. Mark Anderson and Peter Mohler explore new ways of targeting calcium-mediated signaling in the heart—with a focus on combating heart failure by targeting 'local' forms of signaling in heart muscle.

Moving neurons back into place

Nature Medicine 15, 17 (2009). doi:10.1038/nm0109-17

Authors: Geraldine Kerjan & Joseph G Gleeson

Mental retardation and epilepsy can result from the aberrant migration of neurons during development. An experimental treatment in prenatal mice restores normal patterns of migration and eases symptoms (pages 84–90).

Straight talk with...Mervyn Turner

Nature Medicine 15, 8 (2009). doi:10.1038/nm0109-8

Author: Prashant Nair

In recent years, pharmaceutical giants have overcome challenges to innovation by collaborating with small biotechnology firms. These partnerships not only accelerate drug discovery but also help large companies survive competition in the market for generic drugs. Last month, New Jersey–based Merck & Co. announced that the company is launching its own division, Merck BioVentures, to develop generic versions of 'biologics', drugs commonly produced by living cells. Merck acquired some of the technology for the new division by fostering precisely such ties with smaller firms. Merck's newly appointed chief strategy officer, Mervyn Turner, has overseen many of those partnerships during his 23 years at the company. Turner, who holds a doctorate in stereochemistry from Sheffield University, UK, joined the pharmaceutical giant in 1985 as director of its biochemical parasitology unit. He has since led part of Merck's basic and applied research and supervised all of the licensing of research conducted outside the company. Turner spoke with Prashant Nair about the future promise of drug development and about how pharmaceutical companies can cope with the current economic downturn.

Corrigendum: Eradication of acute promyelocytic leukemia-initiating cells through PML-RARA degradation

Nature Medicine 15, 117 (2009). doi:10.1038/nm0109-117b

Authors: 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

Mended Armor

Nature Medicine 15, 10 (2009). doi:10.1038/nm0109-10

Author: Laura Spinney

A growing body of evidence supports the idea that some infectious diseases have a heritable component, a notion put forth by none other than Louis Pasteur. As scientists begin to catalog the genetic changes that predispose people to specific illnesses, they are also exploring how to prevent sickness by replacing the missing parts of the immune system's defensive armor. Laura Spinney reports.

Mesenchymal stem cells combat sepsis

Nature Medicine 15, 18 (2009). doi:10.1038/nm0109-18

Authors: Alan Tyndall & Vito Pistoia

A new approach to the treatment of sepsis relies on the infusion of mesenchymal stem cells, multipotent cells used experimentally to treat a range of medical conditions. In mouse models, the cells seem to reprogram immune cells that can contribute to sepsis (pages 42–49).

Fixing a failed vaccine

Nature Medicine 15, 21 (2009). doi:10.1038/nm0109-21

Author: Steven M Varga

A trial of a childhood vaccine against a common respiratory virus went terribly wrong in the early 1960s. Instead of protecting children, the vaccine exacerbated disease in response to infection. We now have a better understanding as to why (pages 34–41).

Erratum: BMP type I receptor inhibition reduces heterotopic ossification

Nature Medicine 15, 117 (2009). doi:10.1038/nm0109-117a

Authors: 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

New Year's resolutions

Nature Medicine 15, 1 (2009). doi:10.1038/nm0109-1

Here are a few of the things that Nature Medicine is looking forward to during 2009.

A pipe dream becomes reality

Nature Medicine 15, 4 (2009). doi:10.1038/nm0109-4b

News in brief

Nature Medicine 15, 6 (2009). doi:10.1038/nm0109-6

Cancer stem cells are everywhere

Nature Medicine 15, 23 (2009). doi:10.1038/nm0109-23

Research Highlights

Nature Medicine 15, 28 (2009). doi:10.1038/nm0109-28

Decreased levels of microRNA miR-122 in individuals with hepatitis C responding poorly to interferon therapy

Nature Medicine 15, 31 (2009). doi:10.1038/nm.1902

Authors: Magdalena Sarasin-Filipowicz, Jacek Krol, Ilona Markiewicz, Markus H Heim & Witold Filipowicz

Several microRNAs (miRNAs), including liver-specific miR-122, have been implicated in the control of hepatitis C virus (HCV) RNA replication and its response to interferon (IFN) in human hepatoma cells. Our analysis of liver biopsies from subjects with chronic hepatitis C (CHC) undergoing IFN therapy revealed no correlation of miR-122 expression with viral load and markedly decreased pretreatment miR-122 levels in subjects who had no virological response during later IFN therapy; other investigated miRNAs showed only limited changes. These data have implications for the prospect of targeting miRNAs for CHC therapy.

A stroma-related gene signature predicts resistance to neoadjuvant chemotherapy in breast cancer

Nature Medicine 15, 68 (2009). doi:10.1038/nm.1908

Authors: Pierre Farmer, Hervé Bonnefoi, Pascale Anderle, David Cameron, Pratyakasha Wirapati, Véronique Becette, Sylvie André, Martine Piccart, Mario Campone, Etienne Brain, Gaëtan MacGrogan, Thierry Petit, Jacek Jassem, Frédéric Bibeau, Emmanuel Blot, Jan Bogaerts, Michel Aguet, Jonas Bergh, Richard Iggo & Mauro Delorenzi

Disrupting functional interactions between platelet chemokines inhibits atherosclerosis in hyperlipidemic mice

Nature Medicine 15, 97 (2009). doi:10.1038/nm.1898

Authors: Rory R Koenen, Philipp von Hundelshausen, Irina V Nesmelova, Alma Zernecke, Elisa A Liehn, Alisina Sarabi, Birgit K Kramp, Anna M Piccinini, Søren R Paludan, M Anna Kowalska, Andreas J Kungl, Tilman M Hackeng, Kevin H Mayo & Christian Weber

Atherosclerosis is characterized by chronic inflammation of the arterial wall due to chemokine-driven mononuclear cell recruitment. Activated platelets can synergize with chemokines to exacerbate atherogenesis; for example, by deposition of the chemokines platelet factor-4 (PF4, also known as CXCL4) and RANTES (CCL5), triggering monocyte arrest on inflamed endothelium. Homo-oligomerization is required for the recruitment functions of CCL5, and chemokine heteromerization has more recently emerged as an additional regulatory mechanism, as evidenced by a mutual modulation of CXCL8 and CXCL4 activities and by enhanced monocyte arrest resulting from CCL5-CXCL4 interactions. The CCL5 antagonist Met-RANTES reduces diet-induced atherosclerosis; however, CCL5 antagonism may not be therapeutically feasible, as suggested by studies using Ccl5-deficient mice which imply that direct CCL5 blockade would severely compromise systemic immune responses, delay macrophage-mediated viral clearance and impair normal T cell functions. Here we determined structural features of CCL5-CXCL4 heteromers and designed stable peptide inhibitors that specifically disrupt proinflammatory CCL5-CXCL4 interactions, thereby attenuating monocyte recruitment and reducing atherosclerosis without the aforementioned side effects. These results establish the in vivo relevance of chemokine heteromers and show the potential of targeting heteromer formation to achieve therapeutic effects.

Development of a novel mouse glioma model using lentiviral vectors

Nature Medicine 15, 110 (2009). doi:10.1038/nm.1863

Authors: Tomotoshi Marumoto, Ayumu Tashiro, Dinorah Friedmann-Morvinski, Miriam Scadeng, Yasushi Soda, Fred H Gage & Inder M Verma

Dcx reexpression reduces subcortical band heterotopia and seizure threshold in an animal model of neuronal migration disorder

Nature Medicine 15, 84 (2009). doi:10.1038/nm.1897

Authors: Jean-Bernard Manent, Yu Wang, YoonJeung Chang, Murugan Paramasivam & Joseph J LoTurco

γ-secretase inhibitors reverse glucocorticoid resistance in T cell acute lymphoblastic leukemia

Nature Medicine 15, 50 (2009). doi:10.1038/nm.1900

Authors: Pedro J Real, Valeria Tosello, Teresa Palomero, Mireia Castillo, Eva Hernando, Elisa de Stanchina, Maria Luisa Sulis, Kelly Barnes, Catherine Sawai, Irene Homminga, Jules Meijerink, Iannis Aifantis, Giuseppe Basso, Carlos Cordon-Cardo, Walden Ai & Adolfo Ferrando