New Year's resolutions - p1

doi:10.1038/nm0109-1

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

Abstract - | Full Text - New Year's resolutions | PDF (103 KB) - New Year's resolutions

Challenges anticipated in removal of stem cell restrictions - p3

Stu Hutson

doi:10.1038/nm0109-3

Full Text - Challenges anticipated in removal of stem cell restrictions | PDF (330 KB) - Challenges anticipated in removal of stem cell restrictions

Religious leaders weigh in on current and future embryo research - p4

Jon Evans

doi:10.1038/nm0109-4a

Full Text - Religious leaders weigh in on current and future embryo research | PDF (168 KB) - Religious leaders weigh in on current and future embryo research

A pipe dream becomes reality - p4

doi:10.1038/nm0109-4b

Full Text - A pipe dream becomes reality | PDF (168 KB) - A pipe dream becomes reality

HPV researchers set sights on preventing skin cancers - p5

Simon Grose

doi:10.1038/nm0109-5a

Full Text - HPV researchers set sights on preventing skin cancers | PDF (262 KB) - HPV researchers set sights on preventing skin cancers

Report details scientific self-censoring - p5

Genevive Bjorn

doi:10.1038/nm0109-5b

Full Text - Report details scientific self-censoring | PDF (262 KB) - Report details scientific self-censoring

News in brief - pp6 - 7

doi:10.1038/nm0109-6

Full Text - News in brief | PDF (768 KB) - News in brief

Straight talk with...Mervyn Turner - pp8 - 9

Prashant Nair

doi:10.1038/nm0109-8

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.

Abstract - | Full Text - Straight talk with...Mervyn Turner | PDF (427 KB) - Straight talk with...Mervyn Turner

Mended Armor - pp10 - 13

Laura Spinney

doi:10.1038/nm0109-10

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.

Abstract - | Full Text - Mended Armor | PDF (1,240 KB) - Mended Armor

A chemical physicist in biology - p15

Judith Goodstein reviews Max Perutz and the Secret of Life by Georgina Ferry

doi:10.1038/nm0109-15

Full Text - A chemical physicist in biology | PDF (120 KB) - A chemical physicist in biology

Moving neurons back into place - pp17 - 18

Geraldine Kerjan & Joseph G Gleeson

doi:10.1038/nm0109-17

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).

Abstract - | Full Text - Moving neurons back into place | PDF (263 KB) - Moving neurons back into place

See also: Article by Manent et al.

Mesenchymal stem cells combat sepsis - pp18 - 20

Alan Tyndall & Vito Pistoia

doi:10.1038/nm0109-18

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).

Abstract - | Full Text - Mesenchymal stem cells combat sepsis | PDF (1,355 KB) - Mesenchymal stem cells combat sepsis

See also: Article by Németh et al.

-secretase inhibitors: Notch so bad - pp20 - 21

Gerard C Grosveld

doi:10.1038/nm0109-20

-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).

Abstract - | Full Text - -secretase inhibitors: Notch so bad | PDF (244 KB) - -secretase inhibitors: Notch so bad

See also: Article by Real et al.

Fixing a failed vaccine - pp21 - 22

Steven M Varga

doi:10.1038/nm0109-21

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).

Abstract - | Full Text - Fixing a failed vaccine | PDF (500 KB) - Fixing a failed vaccine

See also: Article by Delgado et al.

Cancer stem cells are everywhere - p23

doi:10.1038/nm0109-23

Full Text - Cancer stem cells are everywhere | PDF (364 KB) - Cancer stem cells are everywhere

Rescuing a failing heart: putting on the squeeze - pp24 - 25

David A Kass

doi:10.1038/nm0109-24

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.

Abstract - | Full Text - Rescuing a failing heart: putting on the squeeze | PDF (672 KB) - Rescuing a failing heart: putting on the squeeze

Rescuing a failing heart: think globally, treat locally - pp25 - 26

Mark E Anderson & Peter J Mohler

doi:10.1038/nm0109-25

Full Text - Rescuing a failing heart: think globally, treat locally | PDF (551 KB) - Rescuing a failing heart: think globally, treat locally

Research Highlights - pp28 - 29

doi:10.1038/nm0109-28

Full Text - Research Highlights | PDF (244 KB) - Research Highlights

Decreased levels of microRNA miR-122 in individuals with hepatitis C responding poorly to interferon therapy - pp31 - 33

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

doi:10.1038/nm.1902

Studies of hepatitis C virus replication in cell culture have suggested that certain microRNAs are required for efficient virus replication and that they may be involved in the antiviral effect of interferon. A study in humans infected with the virus provides a new perspective.

Abstract - | Full Text - Decreased levels of microRNA miR-122 in individuals with hepatitis C responding poorly to interferon therapy | PDF (376 KB) - Decreased levels of microRNA miR-122 in individuals with hepatitis C responding poorly to interferon therapy | Supplementary information

Lack of antibody affinity maturation due to poor Toll-like receptor stimulation leads to enhanced respiratory syncytial virus disease - pp34 - 41

Maria Florencia Delgado, Silvina Coviello, A Clara Monsalvo, Guillermina A Melendi, Johanna Zea Hernandez, Juan P Batalle, Leandro Diaz, Alfonsina Trento, Herng-Yu Chang, Wayne Mitzner, Jeffrey Ravetch, José A Melero, Pablo M Irusta & Fernando P Polack

doi:10.1038/nm.1894

A formalin-inactivated vaccine from the 1960s against respiratory syncytial virus (RSV) failed to protect children. Although scientists thought that its failure resulted from formalin disruption of protective antigens, it is now shown that it resulted from low antibody avidity for protective epitopes after poor Toll-like receptor (TLR) stimulation. RSV vaccines could therefore become effective by including TLR agonists in their formulation (pages 21–22).

Abstract - | Full Text - Lack of antibody affinity maturation due to poor Toll-like receptor stimulation leads to enhanced respiratory syncytial virus disease | PDF (773 KB) - Lack of antibody affinity maturation due to poor Toll-like receptor stimulation leads to enhanced respiratory syncytial virus disease | Supplementary information

See also: News and Views by Varga

Bone marrow stromal cells attenuate sepsis via prostaglandin E₂–dependent reprogramming of host macrophages to increase their interleukin-10 production - pp42 - 49

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/nm.1905

Mesenchymal stem cells have therapeutic effects in various different models of disease, but how they work is not always clear. Eva Mezey and her colleagues now propose that such cells may prove beneficial in sepsis—and they work by reprogramming innate immune cells (pages 18–20).

Abstract - | Full Text - Bone marrow stromal cells attenuate sepsis via prostaglandin E2–dependent reprogramming of host macrophages to increase their interleukin-10 production | PDF (719 KB) - Bone marrow stromal cells attenuate sepsis via prostaglandin E2–dependent reprogramming of host macrophages to increase their interleukin-10 production | Supplementary information

See also: News and Views by Tyndall & Pistoia

-secretase inhibitors reverse glucocorticoid resistance in T cell acute lymphoblastic leukemia - pp50 - 58

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

doi:10.1038/nm.1900

Notch signaling has a crucial role in T cell acute lymphoblastic leukemia (T-ALL), but -secretase inhibitors (GSIs), which block the Notch pathway, cause intestinal toxicity that limits their use. Adolfo Ferrando and his colleagues now report that glucocorticoids can reverse the gut toxicity of GSIs, and GSIs can restore sensitivity of T-ALL cells to glucocorticoids, suggesting that this combination may have clinical utility in T-ALL and other diseases (pages 20–21).

Abstract - | Full Text - -secretase inhibitors reverse glucocorticoid resistance in T cell acute lymphoblastic leukemia | PDF (796 KB) - -secretase inhibitors reverse glucocorticoid resistance in T cell acute lymphoblastic leukemia | Supplementary information

See also: News and Views by Grosveld

MACC1, a newly identified key regulator of HGF-MET signaling, predicts colon cancer metastasis - pp59 - 67

Ulrike Stein, Wolfgang Walther, Franziska Arlt, Holger Schwabe, Janice Smith, Iduna Fichtner, Walter Birchmeier & Peter M Schlag

doi:10.1038/nm.1889

Early identification of individuals with colorectal cancer who are at high risk of metastasis might help guide treatment choice and improve outcome. Stein et al. now report that MACC1, a previously undescribed gene, is a prognostic indicator of colorectal cancer and describe its role as a transcriptional regulator of MET, which encodes the hepatocyte growth factor receptor and promotes metastasis of a variety of cancers.

Abstract - | Full Text - MACC1, a newly identified key regulator of HGF-MET signaling, predicts colon cancer metastasis | PDF (1,204 KB) - MACC1, a newly identified key regulator of HGF-MET signaling, predicts colon cancer metastasis | Supplementary information

A stroma-related gene signature predicts resistance to neoadjuvant chemotherapy in breast cancer - pp68 - 74

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

doi:10.1038/nm.1908

Identifying factors that influence response to cancer chemotherapy is crucial for improving its efficacy. Mauro Delorenzi and his colleagues report that a stromal gene expression signature predicts resistance to a commonly used chemotherapy regimen in individuals with estrogen receptor–negative breast tumors. These findings underline the potential of the tumor microenvironment to modulate tumor phenotype and the clinical response to treatment.

Abstract - | Full Text - A stroma-related gene signature predicts resistance to neoadjuvant chemotherapy in breast cancer | PDF (556 KB) - A stroma-related gene signature predicts resistance to neoadjuvant chemotherapy in breast cancer | Supplementary information

A new type of ERK1/2 autophosphorylation causes cardiac hypertrophy - pp75 - 83

Kristina Lorenz, Joachim P Schmitt, Eva M Schmitteckert & Martin J Lohse

doi:10.1038/nm.1893

Mitogen-activated protein (MAP) kinases are known to promote cardiac hypertrophy, but how upstream hypertrophic signals induce these kinases to cause hypertrophy has not been clear. Lorenz et al. now uncover a new mechanism of MAP kinase activation and demonstrate the crucial role that this mechanism has in the hypertrophic response.

Abstract - | Full Text - A new type of ERK1/2 autophosphorylation causes cardiac hypertrophy | PDF (683 KB) - A new type of ERK1/2 autophosphorylation causes cardiac hypertrophy | Supplementary information

Dcx reexpression reduces subcortical band heterotopia and seizure threshold in an animal model of neuronal migration disorder - pp84 - 90

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

doi:10.1038/nm.1897

Aberrant neuronal migration during development leads to defects in cortical development and to an increased seizure susceptibility. Now, Joseph LoTurco and his colleagues show that it is possible to re-invoke neuronal migration perinatally in rodents and reposition neurons into their correct cortical location (pages 17–18).

Abstract - | Full Text - Dcx reexpression reduces subcortical band heterotopia and seizure threshold in an animal model of neuronal migration disorder | PDF (891 KB) - Dcx reexpression reduces subcortical band heterotopia and seizure threshold in an animal model of neuronal migration disorder | Supplementary information

See also: News and Views by Kerjan & Gleeson

Neurotoxic autoantibodies mediate congenital cortical impairment of offspring in maternal lupus - pp91 - 96

Ji Y Lee, Patricio T Huerta, Jie Zhang, Czeslawa Kowal, Eva Bertini, Bruce T Volpe & Betty Diamond

doi:10.1038/nm.1892

Children born to mothers with lupus have a higher rate of learning disorders. Now, in mouse studies, Betty Diamond and her colleagues show that neurotoxic antibodies found in mothers with lupus are transferred to the brains of their offspring. This leads to abnormalities in cortical formation during development and in cognitive function when the pups become adults.

First Paragraph - | Full Text - Neurotoxic autoantibodies mediate congenital cortical impairment of offspring in maternal lupus | PDF (604 KB) - Neurotoxic autoantibodies mediate congenital cortical impairment of offspring in maternal lupus | Supplementary information

Disrupting functional interactions between platelet chemokines inhibits atherosclerosis in hyperlipidemic mice - pp97 - 103

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

doi:10.1038/nm.1898

The chemokines CCL5 and CXCL4 promote monocyte recruitment to atherosclerotic plaques. Recent findings in vitro have shown that heteromerization of CCL5 and CXCL4 increases their potency in stimulating monocyte adhesion and chemotaxis. Koenen et al. now show that this heteromerization has functional consequences in vivo. Treatment of atherosclerotic mice with a cyclic peptide that specifically disrupts the CCL5-CXCL4 interaction inhibited monocyte recruitment to atherosclerotic plaques. Moreover, selective inhibition of heteromer formation may offer therapeutic advantages compared to complete blockade of chemokine function.

First Paragraph - | Full Text - Disrupting functional interactions between platelet chemokines inhibits atherosclerosis in hyperlipidemic mice | PDF (602 KB) - Disrupting functional interactions between platelet chemokines inhibits atherosclerosis in hyperlipidemic mice | Supplementary information

Selective molecular imaging of viable cancer cells with pH-activatable fluorescence probes - pp104 - 109

Yasuteru Urano, Daisuke Asanuma, Yukihiro Hama, Yoshinori Koyama, Tristan Barrett, Mako Kamiya, Tetsuo Nagano, Toshiaki Watanabe, Akira Hasegawa, Peter L Choyke & Hisataka Kobayashi

doi:10.1038/nm.1854

A goal of cancer research is to develop specific and sensitive tumor-imaging techniques for early detection while minimizing background signals from nontarget, 'normal' tissues. The authors have designed a 'pH-activatable' probe, consisting of a targeted macromolecule (monoclonal antibody) and a fluorescence probe, which is activated after internalization in the lysosomes of targeted cancer cells. The utility of this approach for imaging HER2-positive lung cancer cells in mice is shown.

First Paragraph - | Full Text - Selective molecular imaging of viable cancer cells with pH-activatable fluorescence probes | PDF (865 KB) - Selective molecular imaging of viable cancer cells with pH-activatable fluorescence probes | Supplementary information

Development of a novel mouse glioma model using lentiviral vectors - pp110 - 116

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

doi:10.1038/nm.1863

There is a need for mouse tumor models that more closely recapitulate the pathophysiology of human cancers. Here, a mouse model of glioblastoma multiforme (GBM) is generated with Cre-loxP controlled, lentiviral-mediated delivery of the oncogenes H-Ras and AKT. Transduction of the oncogenes in a small number of cells in adult immunocompetent mice led to the formation of GBM-like tumors, particularly when combined with loss of p53.

Abstract - | Full Text - Development of a novel mouse glioma model using lentiviral vectors | PDF (1,037 KB) - Development of a novel mouse glioma model using lentiviral vectors | Supplementary information

Erratum: BMP type I receptor inhibition reduces heterotopic ossification - p117

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/nm0109-117a

Full Text - Erratum: BMP type I receptor inhibition reduces heterotopic ossification | PDF (60 KB) - Erratum: BMP type I receptor inhibition reduces heterotopic ossification

Corrigendum: Eradication of acute promyelocytic leukemia-initiating cells through PML-RARA degradation - p117

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/nm0109-117b

Full Text - Corrigendum: Eradication of acute promyelocytic leukemia-initiating cells through PML-RARA degradation | PDF (60 KB) - Corrigendum: Eradication of acute promyelocytic leukemia-initiating cells through PML-RARA degradation