Opposing effects of HLA class I molecules in tuning autoreactive CD8+ T cells in multiple sclerosis

Nature Medicine 14, 1227 (2008). doi:10.1038/nm.1881

Authors: Manuel A Friese, Karen B Jakobsen, Lone Friis, Ruth Etzensperger, Matthew J Craner, Róisín M McMahon, Lise T Jensen, Véronique Huygelen, E Yvonne Jones, John I Bell & Lars Fugger

Suppressed NFAT-dependent VEGFR1 expression and constitutive VEGFR2 signaling in infantile hemangioma

Nature Medicine 14, 1236 (2008). doi:10.1038/nm.1877

Authors: Masatoshi Jinnin, Damian Medici, Lucy Park, Nisha Limaye, Yanqiu Liu, Elisa Boscolo, Joyce Bischoff, Miikka Vikkula, Eileen Boye & Bjorn R Olsen

Niemann-Pick disease type C1 is a sphingosine storage disease that causes deregulation of lysosomal calcium

Nature Medicine 14, 1247 (2008). doi:10.1038/nm.1876

Authors: Emyr Lloyd-Evans, Anthony J Morgan, Xingxuan He, David A Smith, Elena Elliot-Smith, Daniel J Sillence, Grant C Churchill, Edward H Schuchman, Antony Galione & Frances M Platt

5′-triphosphate-siRNA: turning gene silencing and Rig-I activation against melanoma

Nature Medicine 14, 1256 (2008). doi:10.1038/nm.1887

Authors: Hendrik Poeck, Robert Besch, Cornelius Maihoefer, Marcel Renn, Damia Tormo, Svetlana Shulga Morskaya, Susanne Kirschnek, Evelyn Gaffal, Jennifer Landsberg, Johannes Hellmuth, Andreas Schmidt, David Anz, Michael Bscheider, Tobias Schwerd, Carola Berking, Carole Bourquin, Ulrich Kalinke, Elisabeth Kremmer, Hiroki Kato, Shizuo Akira, Rachel Meyers, Georg Häcker, Michael Neuenhahn, Dirk Busch, Jürgen Ruland, Simon Rothenfusser, Marco Prinz, Veit Hornung, Stefan Endres, Thomas Tüting & Gunther Hartmann

Virus-specific T cells engineered to coexpress tumor-specific receptors: persistence and antitumor activity in individuals with neuroblastoma

Nature Medicine 14, 1264 (2008). doi:10.1038/nm.1882

Authors: Martin A Pule, Barbara Savoldo, G Doug Myers, Claudia Rossig, Heidi V Russell, Gianpietro Dotti, M Helen Huls, Enli Liu, Adrian P Gee, Zhuyong Mei, Eric Yvon, Heidi L Weiss, Hao Liu, Cliona M Rooney, Helen E Heslop & Malcolm K Brenner

The miR-15a–miR-16-1 cluster controls prostate cancer by targeting multiple oncogenic activities

Nature Medicine 14, 1271 (2008). doi:10.1038/nm.1880

Authors: Désirée Bonci, Valeria Coppola, Maria Musumeci, Antonio Addario, Raffaella Giuffrida, Lorenzo Memeo, Leonardo D'Urso, Alfredo Pagliuca, Mauro Biffoni, Catherine Labbaye, Monica Bartucci, Giovanni Muto, Cesare Peschle & Ruggero De Maria

MicroRNAs (miRNAs) are noncoding small RNAs that repress protein translation by targeting specific messenger RNAs. miR-15a and miR-16-1 act as putative tumor suppressors by targeting the oncogene BCL2. These miRNAs form a cluster at the chromosomal region 13q14, which is frequently deleted in cancer. Here, we report that the miR-15a and miR-16-1 cluster targets CCND1 (encoding cyclin D1) and WNT3A, which promotes several tumorigenic features such as survival, proliferation and invasion. In cancer cells of advanced prostate tumors, the miR-15a and miR-16 level is significantly decreased, whereas the expression of BCL2, CCND1 and WNT3A is inversely upregulated. Delivery of antagomirs specific for miR-15a and miR-16 to normal mouse prostate results in marked hyperplasia, and knockdown of miR-15a and miR-16 promotes survival, proliferation and invasiveness of untransformed prostate cells, which become tumorigenic in immunodeficient NOD-SCID mice. Conversely, reconstitution of miR-15a and miR-16-1 expression results in growth arrest, apoptosis and marked regression of prostate tumor xenografts. Altogether, we propose that miR-15a and miR-16 act as tumor suppressor genes in prostate cancer through the control of cell survival, proliferation and invasion. These findings have therapeutic implications and may be exploited for future treatment of prostate cancer.

HIT: a versatile proteomics platform for multianalyte phenotyping of cytokines, intracellular proteins and surface molecules

Nature Medicine 14, 1284 (2008). doi:10.1038/nm.1755

Authors: Michael G Kattah, John Coller, Regina K Cheung, Neekaan Oshidary & Paul J Utz

Engineering microRNA responsiveness to decrease virus pathogenicity

Nature Medicine 14, 1278 (2008). doi:10.1038/nm.1776

Authors: Elizabeth J Kelly, Elizabeth M Hadac, Suzanne Greiner & Stephen J Russell

Straight talk with...Ray Moynihan

Nature Medicine 14, 1142 (2008). doi:10.1038/nm1108-1142

Author: Genevive Bjorn

The relationship between pharmaceutical companies and medical professionals has become too close for comfort, say many experts. They fear that the situation can breed conflicts of interest that lead to the creation of new, poorly defined concepts of illnesses—so called 'disease mongering'. The problem is a growing one, according to Ray Moynihan, honorary lecturer on topics such as 'medicine and the media' at the School of Medicine and Public Health at the University of Newcastle in Callaghan, Australia and co-author of the book Selling Sickness: How the World's Biggest Pharmaceutical Companies Are Turning Us All into Patients. Genevive Bjorn talked with Moynihan, who helped organize the first world conference on disease mongering, about how this phenomenon affects health priorities.

Graft-versus-host disease: suppression by statins

Nature Medicine 14, 1155 (2008). doi:10.1038/nm1108-1155

Authors: Raewyn Broady & Megan K Levings

Two big challenges of transplantation biology are controlling the reaction of the graft to the host after hematopoietic stem cell transplantation and preventing rejection of donor organs by the host. Raewyn Broady and Megan K. Levings discuss the first challenge, examining studies suggesting that statins might be helpful to control graft-versus-host disease. Kathryn Wood tackles the second challenge in the context of the 'Edmonton protocol', a procedure that can restore the ability to control blood glucose in people with type 1 diabetes—but only in the short term.

Advances in fertility preservation for female cancer survivors

Nature Medicine 14, 1182 (2008). doi:10.1038/nm1108-1182

Authors: Mats Brännström & Milan Milenkovic

A method using tissue engineering principles for the culture of immature ovarian follicles followed by fertilization of oocytes in vitro has been presented by Xu et al.. This methodology is a great step forward toward new technology for fertility preservation in female cancer patients.

Healing hemangiomas

Nature Medicine 14, 1147 (2008). doi:10.1038/nm1108-1147

Author: Lena Claesson-Welsh

Defective signaling of vascular endothelial growth factor seems to underlie the development of hemangiomas, disfiguring tumors arising early in life (pages 1236–1246).

From stem cells to germ cells and back again

Nature Medicine 14, 1188 (2008). doi:10.1038/nm1108-1188

Authors: Marco Conti & Linda Giudice

Producing germ cells in vitro would open important new avenues for regenerative medicine, and obtaining alternative sources of pluripotent stem cells is desirable. In this regard, Geijsen et al. have shown that it is possible to differentiate stem cells into cells similar to male gametes, whereas Guan et al. reported the ability to turn undifferentiated germ cells into pluripotent stem cells.

European funding for reproduction research—A multinational perspective

Nature Medicine 14, 1224 (2008). doi:10.1038/nm1108-1224a

Authors: Hilary Critchley & Philippa Saunders

Funds from the European Union are not the only source available to the continent's reproductive research community. Each country independently sponsors the work of these scientists, but, as illustrated by snapshots in the following pages, there are huge differences in the commitment of the various European nations to tackle the challenges of reproductive biomedicine.

European funding for reproduction research—A multinational perspective

Nature Medicine 14, 1222 (2008). doi:10.1038/nm1108-1222b

Author: Thomas M D'Hooghe

Funds from the European Union are not the only source available to the continent's reproductive research community. Each country independently sponsors the work of these scientists, but, as illustrated by snapshots in the following pages, there are huge differences in the commitment of the various European nations to tackle the challenges of reproductive biomedicine.

Two faces of PTEN

Nature Medicine 14, 1192 (2008). doi:10.1038/nm1108-1192

Authors: Takiko Daikoku & Sudhansu K Dey

A small number of women (approximately 1%) suffer from premature ovarian failure in which their ovarian follicle reserve is exhausted before age 40. Recent studies in mice show that the absence of a tumor suppressor gene, PTEN, in oocytes prematurely induces global follicular activation, depleting the follicle reserve in a manner similar to premature ovarian failure.

Angiogenesis factors and preeclampsia

Nature Medicine 14, 1187 (2008). doi:10.1038/nm1108-1187

Authors: Ralf Dechend & Friedrich C Luft

Two recent studies—one in humans by Levine et al. in 2004 and one in mice by Venkatesha et al. in 2006—have shown an important role for placental-derived soluble antiangiogenic factors as mediators of the pathologies associated with preeclampsia. These findings may have profound implications for the diagnosis, treatment and prevention of this devastating condition.

The upside of natural killers

Nature Medicine 14, 1184 (2008). doi:10.1038/nm1108-1184

Authors: Khalil Karimi, Sandra M Blois & Petra C Arck

Natural killer (NK) cells, originally so named because they have the capacity to kill other cells without activation, can be licensed and educated to regulate tissue homeostasis. This notion has recently been shown in reproduction—in both normal physiology by Hanna et al. and severe pathophysiology (preeclampsia) by Hiby et al.

European funding for reproduction research—A multinational perspective

Nature Medicine 14, 1223 (2008). doi:10.1038/nm1108-1223b

Author: Antonis Makrigiannakis

Funds from the European Union are not the only source available to the continent's reproductive research community. Each country independently sponsors the work of these scientists, but, as illustrated by snapshots in the following pages, there are huge differences in the commitment of the various European nations to tackle the challenges of reproductive biomedicine.

HLA class I: friend and foe of multiple sclerosis

Nature Medicine 14, 1150 (2008). doi:10.1038/nm1108-1150

Author: Roland Martin

Findings in a mouse model of multiple sclerosis highlight the contribution of CD8+ T cells, previously largely ignored in this disease. The work also helps answer why certain variants of the human leukocyte antigen (HLA) complex are protective, while others increase risk for disease (pages 1227–1235).

Epstein-Barr virus sustains tumor killers

Nature Medicine 14, 1148 (2008). doi:10.1038/nm1108-1148

Author: Richard J O'Reilly

The immune system's response to a latent and ubiquitous virus is harnessed to kill tumors in a small study of humans. The approach overcomes a major barrier to effective tumor immunotherapy—generating a sustained immune response (pages 1264–1270).

RIG-ing an antitumor response

Nature Medicine 14, 1152 (2008). doi:10.1038/nm1108-1152

Authors: Fabio Petrocca & Judy Lieberman

A small interfering RNA has been engineered to silence an oncogene and activate the immune response simultaneously. The approach shrinks tumors in mice (pages 1256–1263).

Is it my grandparents' fault?

Nature Medicine 14, 1186 (2008). doi:10.1038/nm1108-1186

Author: Bernard Robaire

Results from two independent groups of researchers have revolutionized our thinking about the potential long-term consequences of exposure to common foreign chemicals, or xenobiotics. The studies indicate that exposure to such chemicals during key windows of gestation can affect not only the children exposed in utero but also their children and perhaps even their grandchildren.

European funding for reproduction research—A multinational perspective

Nature Medicine 14, 1223 (2008). doi:10.1038/nm1108-1223a

Author: Daniel Rukavina

Funds from the European Union are not the only source available to the continent's reproductive research community. Each country independently sponsors the work of these scientists, but, as illustrated by snapshots in the following pages, there are huge differences in the commitment of the various European nations to tackle the challenges of reproductive biomedicine.

European funding for reproduction research—A multinational perspective

Nature Medicine 14, 1222 (2008). doi:10.1038/nm1108-1222a

Author: Carlos Simón

Funds from the European Union are not the only source available to the continent's reproductive research community. Each country independently sponsors the work of these scientists, but, as illustrated by snapshots in the following pages, there are huge differences in the commitment of the various European nations to tackle the challenges of reproductive biomedicine.

European funding for reproduction research—A multinational perspective

Nature Medicine 14, 1224 (2008). doi:10.1038/nm1108-1224b

Author: Thomas Strowitzki

Funds from the European Union are not the only source available to the continent's reproductive research community. Each country independently sponsors the work of these scientists, but, as illustrated by snapshots in the following pages, there are huge differences in the commitment of the various European nations to tackle the challenges of reproductive biomedicine.

Timeline: the role of kisspeptins in reproductive biology

Nature Medicine 14, 1196 (2008). doi:10.1038/nm1108-1196

Author: Manuel Tena-Sempere

Although the focus of this issue is on contributions published over the past three to four years, the discovery of the kisspeptins was hailed as an important breakthrough by our advisors so frequently that we had to include it. Manuel Tena-Sempere guides us on a tour of the key findings that have shaped this blossoming field.

Making eggs: is it now or later?

Nature Medicine 14, 1190 (2008). doi:10.1038/nm1108-1190

Author: Teresa K Woodruff

Although it has been thought that female mammals develop all the eggs they will ever have by the time they are born, new research suggesting otherwise has now sparked a debate.

Research and recovery

Nature Medicine 14, 1129 (2008). doi:10.1038/nm1108-1129

The global economy is in trouble. Investment in biomedical research should be a key ingredient in any recovery plan.

The chronic debate over Lyme disease

Nature Medicine 14, 1135 (2008). doi:10.1038/nm1108-1135

A small group of doctors—and a large number of patients—say Lyme disease can sometimes manifest as a chronic illness, one that evades conventional medical tests and treatments. The physicians who support this theory flout standard medical guidelines and treat patients with long-term antibiotic therapies that mainstream researchers say are unproven and potentially dangerous. Coco Ballantyne reports on how the controversy over Lyme disease has become increasing polarized.

Reproductive biology

Nature Medicine 14, 1166 (2008). doi:10.1038/nm1108-1166

In what direction is the field of reproductive biology moving? Do funding priorities match hot research areas? In this special focus, we try to find out.

The top papers on reproduction research 2004–2008

Nature Medicine 14, 1178 (2008). doi:10.1038/nm1108-1178

Which papers have provided the most interesting advances in reproduction research over the past three or four years? Which new discoveries have been the most important to or are likely to have the highest impact on the field?