Table of contents


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Focus

Focus on Reproductive Biology

In what direction is the field of reproductive biology going? By bringing together input from top scientists and decision makers interested in this field, this focus identifies the recent papers with the most impact in reproductive biology and identifies the key issues that are shaping our thinking in this field.

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Editorial

Research and recovery p1129

doi:10.1038/nm1108-1129

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


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News

US researchers await key science appointments by next president p1131

Amber Dance

doi:10.1038/nm1108-1131


China takes first steps toward healthcare and drug reforms p1132

Virginia Hughes

doi:10.1038/nm1108-1132a


Nobel decision stirs viral dismay p1132

Coco Ballantyne

doi:10.1038/nm1108-1132b


India plans for interdisciplinary neuroscience research center p1133

TV Padma

doi:10.1038/nm1108-1133a


Publication is positively skewed p1133

Genevive Bjorn

doi:10.1038/nm1108-1133b


Australia grants license for therapeutic cloning p1134

Simon Grose

doi:10.1038/nm1108-1134a


Safer stem cells p1134

Genevive Bjorn

doi:10.1038/nm1108-1134b


The chronic debate over Lyme disease pp1135 - 1139

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.


News in brief pp1140 - 1141

doi:10.1038/nm1108-1140


Straight talk with...Ray Moynihan pp1142 - 1143

Genevive Bjorn

doi:10.1038/nm1108-1142

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.


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Book Review

Putting alternative medicine to the test p1145

Brian Dolan reviews Snake Oil Science: The Truth About Complementary and Alternative Medicine by R. Barker Bausell

doi:10.1038/nm1108-1145


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News and Views

Healing hemangiomas pp1147 - 1148

Lena Claesson-Welsh

doi:10.1038/nm1108-1147

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

See also: Article by Jinnin et al.


Epstein-Barr virus sustains tumor killers pp1148 - 1150

Richard J O'Reilly

doi:10.1038/nm1108-1148

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).

See also: Article by Pule et al.


HLA class I: friend and foe of multiple sclerosis pp1150 - 1151

Roland Martin

doi:10.1038/nm1108-1150

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).

See also: Article by Friese et al.


RIG-ing an antitumor response pp1152 - 1153

Fabio Petrocca & Judy Lieberman

doi:10.1038/nm1108-1152

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).

See also: Article by Poeck et al.


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Community Corner

Community corner p1154

doi:10.1038/nm1108-1154


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Between Bedside and Bench

Graft-versus-host disease: suppression by statins pp1155 - 1156

Raewyn Broady & Megan K Levings

doi:10.1038/nm1108-1155

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.


Outlook for longer-lasting islets pp1156 - 1157

Kathryn Wood

doi:10.1038/nm1108-1156


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Research Highlights

Research Highlights pp1158 - 1159

doi:10.1038/nm1108-1158


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Introduction

Focus on Reproductive Biology

Reproductive biology p1166

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.


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News

Focus on Reproductive Biology

As obesity epidemic grows, research shows fitness benefits fetal development p1167

Genevive Bjorn

doi:10.1038/nm1108-1167


Focus on Reproductive Biology

Interventions might offer a pregnant pause in addiction p1168

Erika Check Hayden

doi:10.1038/nm1108-1168


Focus on Reproductive Biology

Better tests boost IVF success p1169

Coco Ballantyne

doi:10.1038/nm1108-1169a


Focus on Reproductive Biology

Delivery decision is nothing to sneeze at p1169

doi:10.1038/nm1108-1169b


Focus on Reproductive Biology

Male biological clock possibly linked to autism, other disorders p1170

Charlotte Schubert

doi:10.1038/nm1108-1170a


Focus on Reproductive Biology

New techniques preserve fertility hope for women p1170

Apoorva Mandavilli

doi:10.1038/nm1108-1170b


Focus on Reproductive Biology

As IVF becomes more common, some concerns remain p1171

Prashant Nair

doi:10.1038/nm1108-1171


Focus on Reproductive Biology

Common reproductive disorders may have immunological basis p1172

Alisa Opar

doi:10.1038/nm1108-1172


Focus on Reproductive Biology

My mother's keeper p1173

Coco Ballantyne

doi:10.1038/nm1108-1173


Focus on Reproductive Biology

Geneticists crack the code of infertility p1174

Virginia Hughes

doi:10.1038/nm1108-1174


Data Page

Focus on Reproductive Biology

By the numbers... p1175

doi:10.1038/nm1108-1175


News Feature

Focus on Reproductive Biology

Tinkering in the womb: the future of fetal surgery pp1176 - 1177

Cassandra Willyard

doi:10.1038/nm1108-1176


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Analysis

Focus on Reproductive Biology

The top papers on reproduction research 2004–2008 pp1178 - 1179

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?


Focus on Reproductive Biology

Highly cited papers on reproductive biology (2005–2007) pp1180 - 1181

doi:10.1038/nm1108-1180


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News and Views

Focus on Reproductive Biology

Advances in fertility preservation for female cancer survivors pp1182 - 1184

Mats Brännström & Milan Milenkovic

doi:10.1038/nm1108-1182

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.1. This methodology is a great step forward toward new technology for fertility preservation in female cancer patients.


Focus on Reproductive Biology

The upside of natural killers pp1184 - 1185

Khalil Karimi, Sandra M Blois & Petra C Arck

doi:10.1038/nm1108-1184

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.


Focus on Reproductive Biology

Is it my grandparents' fault? pp1186 - 1187

Bernard Robaire

doi:10.1038/nm1108-1186

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.


Focus on Reproductive Biology

Angiogenesis factors and preeclampsia pp1187 - 1188

Ralf Dechend & Friedrich C Luft

doi:10.1038/nm1108-1187

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.


Focus on Reproductive Biology

From stem cells to germ cells and back again pp1188 - 1190

Marco Conti & Linda Giudice

doi:10.1038/nm1108-1188

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.


Focus on Reproductive Biology

Making eggs: is it now or later? pp1190 - 1191

Teresa K Woodruff

doi:10.1038/nm1108-1190

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.


Focus on Reproductive Biology

Two faces of PTEN pp1192 - 1193

Takiko Daikoku & Sudhansu K Dey

doi:10.1038/nm1108-1192

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.


Focus on Reproductive Biology

Research Highlights p1194

doi:10.1038/nm1108-1194


Timeline

Focus on Reproductive Biology

Timeline: the role of kisspeptins in reproductive biology p1196

Manuel Tena-Sempere

doi:10.1038/nm1108-1196

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.


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Review

Focus on Reproductive Biology

The biology of infertility: research advances and clinical challenges pp1197 - 1213

Martin M Matzuk & Dolores J Lamb

doi:10.1038/nm.f.1895


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Commentaries

Focus on Reproductive Biology

Funding for the reproductive sciences in the US pp1214 - 1217

Jerome F Strauss, III & Louis V De Paolo

doi:10.1038/nm1108-1214


Focus on Reproductive Biology

Funding for research in reproduction in the European Union pp1218 - 1220

Gérard Chaouat

doi:10.1038/nm1108-1218


Focus on Reproductive Biology

European funding for reproduction research—A multinational perspective p1222

Carlos Simón

doi:10.1038/nm1108-1222a

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.


Focus on Reproductive Biology

European funding for reproduction research—A multinational perspective p1222

Thomas M D'Hooghe

doi:10.1038/nm1108-1222b

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.


Focus on Reproductive Biology

European funding for reproduction research—A multinational perspective p1223

Daniel Rukavina

doi:10.1038/nm1108-1223a

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.


Focus on Reproductive Biology

European funding for reproduction research—A multinational perspective p1223

Antonis Makrigiannakis

doi:10.1038/nm1108-1223b

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.


Focus on Reproductive Biology

European funding for reproduction research—A multinational perspective p1224

Hilary Critchley & Philippa Saunders

doi:10.1038/nm1108-1224a

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.


Focus on Reproductive Biology

European funding for reproduction research—A multinational perspective p1224

Thomas Strowitzki

doi:10.1038/nm1108-1224b

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.


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Articles

Opposing effects of HLA class I molecules in tuning autoreactive CD8+ T cells in multiple sclerosis pp1227 - 1235

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

doi:10.1038/nm.1881

Although major histocompatibility complex (MHC) class II alleles and CD4+ T cells have been implicated in multiple sclerosis, Friese et al. provide here the first direct evidence incriminating MHC class I genes and CD8+ T cells in the pathogenesis of this autoimmune disorder (pages 1150–1151).

See also: News and Views by Martin


Suppressed NFAT-dependent VEGFR1 expression and constitutive VEGFR2 signaling in infantile hemangioma pp1236 - 1246

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

doi:10.1038/nm.1877

Bjorn Olsen and his coworkers shed light on the molecular mechanisms underpinning the proangiogenic properties of endothelial cells in hemangiomas, tracing these properties to decreased activity of a signaling pathway involving NFAT transcription factor regulation of VEGFR1 receptor expression. They also identify germline mutations in genes encoding elements of this signaling pathway in a subset of individuals with hemangioma and suggest that interventions in this pathway could have therapeutic effects (pages 1147–1148).

See also: News and Views by Claesson-Welsh


Niemann-Pick disease type C1 is a sphingosine storage disease that causes deregulation of lysosomal calcium pp1247 - 1255

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

doi:10.1038/nm.1876

Niemann-Pick type C1 is a lysosomal storage disease caused by mutations in the NPC1 gene. The authors show that NPC1 regulates calcium levels in the lysosome, and calcium dysregulation could be the proximal event in inducing the accumulation of lipids that characterizes the disease.


5'-triphosphate-siRNA: turning gene silencing and Rig-I activation against melanoma pp1256 - 1263

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

doi:10.1038/nm.1887

siRNA is used to silence expression of a specific gene and, if modified by a triphosphate at the 5' end, will also activate the helicase Rig-I, leading to interferon production. Poeck et al. now combine both of these activities in a single siRNA to kill melanoma cells by crippling a crucial tumor cell survival pathway and triggering an interferon-dependent antitumor immune response (pages 1152–1153).

See also: News and Views by Petrocca & Lieberman


Virus-specific T cells engineered to coexpress tumor-specific receptors: persistence and antitumor activity in individuals with neuroblastoma pp1264 - 1270

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

doi:10.1038/nm.1882

The promise of engineered T cells for treating cancer has been mitigated by their poor persistence when transferred to patients. Pule et al. now show that dual-specific T cells that recognize an Epstein-Barr virus (EBV) antigen and a tumor antigen survive longer in individuals with neuroblastoma. Engineering virus-specific T cells to recognize tumor antigens may improve the efficacy of this immunotherapy in latently infected cancer patients (pages 1148–1150).

See also: News and Views by O'Reilly


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Letter

The miR-15amiR-16-1 cluster controls prostate cancer by targeting multiple oncogenic activities pp1271 - 1277

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

doi:10.1038/nm.1880

Two microRNAs, miR-15a and miR-16, localize to a chromosome region that is frequently deleted in cancer. Bonci et al. now show that these microRNAs have tumor suppressive effects in prostate cancer cells and regulate the expression of crucial oncogenic targets.


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Technical Reports

Engineering microRNA responsiveness to decrease virus pathogenicity pp1278 - 1283

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

doi:10.1038/nm.1776

Kelly et al. offer a method for controlling the tropism of replicating viruses. Viral replication in a specific target tissue is inhibited by incorporation of tissue-specific microRNA targets within the viral genome. Using an oncolytic picornavirus that causes myositis in tumor-bearing mice, they show the virus is unable to replicate in muscle but still retains oncolytic activity, with implications for the clinical use of oncolytic viruses and vaccine development.


HIT: a versatile proteomics platform for multianalyte phenotyping of cytokines, intracellular proteins and surface molecules pp1284 - 1289

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

doi:10.1038/nm.1755

There is a pressing need for better methods to analyze specific proteins in a high-throughput manner. Current approaches involve studying only a few markers at a time. Here Kattah and his colleagues describe a new technology for multiplexed protein detection called high-throughput immunophenotyping using transcription (HIT). Use of this multianalyte, antibody-based protein array platform is demonstrated for profiling cytokines in serum, intracellular signaling molecules and cell surface markers.


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Erratum

Erratum: Straight talk with...Charles Grassley p1290

Meredith Wadman

doi:10.1038/nm1108-1290


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