September 2009 Volume 15 Number 9, pp 975 - 1093
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Infectious disease: Rapamycin's immunostimulatory potential
Despite Rapamune's current use as an immunosuppressant, Emory University researchers think it has promise as an immunostimulatory vaccine adjuvant. Find out more by reading the first in-depth analysis of the scientific and commercial potential of the work in SciBX: Science-Business eXchange.
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NATURE MEDICINE PODCAST
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Juicing up jabs
Listen in to find out how researchers are updating a key component of vaccines to make these shots more effective. Plus, African labs look to the stars, an update on H1N1, and the latest biomedical headlines.
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EDITORIAL
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In the land of the monolingual p975
Translating a basic finding into a new therapy requires us to speak many languages-scientific, clinical, legal and financial. Yet most of us are hopelessly 'monolingual', a limitation that substantially slows translational research. Steps have been taken to address this problem, but a lot remains to be done.
doi:10.1038/nm0909-975
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NEWS
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A change is in the wind as 'adaptive' clinical trials catch on p977
Stu Hutson
doi:10.1038/nm0909-977
http://links.ealert.nature.com/ctt?kn=91&m=33991969&r=MTc2NTQyNDEzOQS2&b=2&j=NTc1ODczNjYS1&mt=1&rt=0
Pandemic vaccine enters clinical trials p978
Cassandra Willyard
doi:10.1038/nm0909-978a
http://links.ealert.nature.com/ctt?kn=89&m=33991969&r=MTc2NTQyNDEzOQS2&b=2&j=NTc1ODczNjYS1&mt=1&rt=0
New plan seeks to accelerate African diagnostic capacity p978
Melinda Wenner
doi:10.1038/nm0909-978b
http://links.ealert.nature.com/ctt?kn=96&m=33991969&r=MTc2NTQyNDEzOQS2&b=2&j=NTc1ODczNjYS1&mt=1&rt=0
Sealants get specific p978
Nayanah Siva
doi:10.1038/nm0909-978c
http://links.ealert.nature.com/ctt?kn=94&m=33991969&r=MTc2NTQyNDEzOQS2&b=2&j=NTc1ODczNjYS1&mt=1&rt=0
New technologies promise safer sex for women p979
Mike May
doi:10.1038/nm0909-979a
http://links.ealert.nature.com/ctt?kn=102&m=33991969&r=MTc2NTQyNDEzOQS2&b=2&j=NTc1ODczNjYS1&mt=1&rt=0
Growing pains plague children's health study p979
Melinda Wenner
doi:10.1038/nm0909-979b
http://links.ealert.nature.com/ctt?kn=101&m=33991969&r=MTc2NTQyNDEzOQS2&b=2&j=NTc1ODczNjYS1&mt=1&rt=0
News in brief pp980 - 981
doi:10.1038/nm0909-980
http://links.ealert.nature.com/ctt?kn=106&m=33991969&r=MTc2NTQyNDEzOQS2&b=2&j=NTc1ODczNjYS1&mt=1&rt=0
Straight talk with...Ian Lipkin pp982 - 983
Erica Westly
doi:10.1038/nm0909-982
Abstract: http://links.ealert.nature.com/ctt?kn=177&m=33991969&r=MTc2NTQyNDEzOQS2&b=2&j=NTc1ODczNjYS1&mt=1&rt=0
Article: http://links.ealert.nature.com/ctt?kn=30&m=33991969&r=MTc2NTQyNDEzOQS2&b=2&j=NTc1ODczNjYS1&mt=1&rt=0
Boosting our best shot pp984 - 988
Vaccines work by training the immune system to target pathogens, but many types of shots need added substances called adjuvants to elicit a robust response. Despite the power of adjuvants, only one, called alum, is approved in the US. Charlotte Schubert looks at recent discoveries that could translate into a wider range of adjuvants and perhaps help provide future protection against diseases ranging from malaria to H1N1 'swine' flu.
Charlotte Schubert
doi:10.1038/nm0909-984
http://links.ealert.nature.com/ctt?kn=33&m=33991969&r=MTc2NTQyNDEzOQS2&b=2&j=NTc1ODczNjYS1&mt=1&rt=0
Illuminating alum p985
Charlotte Schubert
doi:10.1038/nm0909-985
http://links.ealert.nature.com/ctt?kn=24&m=33991969&r=MTc2NTQyNDEzOQS2&b=2&j=NTc1ODczNjYS1&mt=1&rt=0
Swine flu agitates the adjuvant debate pp986 - 987
Charlotte Schubert
doi:10.1038/nm0909-986
http://links.ealert.nature.com/ctt?kn=26&m=33991969&r=MTc2NTQyNDEzOQS2&b=2&j=NTc1ODczNjYS1&mt=1&rt=0
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CORRESPONDENCE
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Mouse fertility is not dependent on the CREB coactivator Crtc1 pp989 - 990
Lionel Breuillaud et al.
doi:10.1038/nm0909-989
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Reply to: "Mouse fertility is not dependent on the CREB coactivator Crtc1" p991
Judith Altarejos et al.
doi:10.1038/nm0909-991a
http://links.ealert.nature.com/ctt?kn=21&m=33991969&r=MTc2NTQyNDEzOQS2&b=2&j=NTc1ODczNjYS1&mt=1&rt=0
Innovating for impact: The Affordable Medicines Facility-malaria (AMFm) p991
Olusoji Adeyi and Rifat Atun
doi:10.1038/nm0909-991b
http://links.ealert.nature.com/ctt?kn=14&m=33991969&r=MTc2NTQyNDEzOQS2&b=2&j=NTc1ODczNjYS1&mt=1&rt=0
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BOOK REVIEW
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The vaccine-autism controversy p992
Daniel Geschwind reviews Autism's False Prophets: Bad Science, Risky Medicine, and the Search for a Cure by Paul A. Offit
doi:10.1038/nm0909-992
http://links.ealert.nature.com/ctt?kn=9&m=33991969&r=MTc2NTQyNDEzOQS2&b=2&j=NTc1ODczNjYS1&mt=1&rt=0
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NEWS AND VIEWS
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Blocking the path of lymphatic vessels pp993 - 994
Identification of an endogenous inhibitor of lymphatic vessel formation provides a glimpse at how lymphatic vessel growth is restrained (pages 1023-1030). The findings might be exploited to lower transplant rejection rates.
Mihaela Skobe and Reza Dana
doi:10.1038/nm0909-993
http://links.ealert.nature.com/ctt?kn=7&m=33991969&r=MTc2NTQyNDEzOQS2&b=2&j=NTc1ODczNjYS1&mt=1&rt=0
Two sides to cilia in cancer pp994 - 996
The primary cilium can keep cancer at bay, or it can instigate tumor development, according to studies in mice (pages 1055-1061 and 1062-1065). The outcome depends on the nature of the initiating event, which involves signaling through the Hedgehog pathway.
Rune Toftgard
doi:10.1038/nm0909-994
http://links.ealert.nature.com/ctt?kn=4&m=33991969&r=MTc2NTQyNDEzOQS2&b=2&j=NTc1ODczNjYS1&mt=1&rt=0
Connecting obesity, aging and diabetes pp996 - 997
Obesity accelerates the aging of adipose tissue, a process only now beginning to come to light at the molecular level. Experiments in mice suggest that obesity increases the formation of reactive oxygen species in fat cells, shortens telomeres-and ultimately results in activation of the p53 tumor suppressor, inflammation and the promotion of insulin resistance (pages 1082-1087).
Rexford S. Ahima
doi:10.1038/nm0909-996
http://links.ealert.nature.com/ctt?kn=49&m=33991969&r=MTc2NTQyNDEzOQS2&b=2&j=NTc1ODczNjYS1&mt=1&rt=0
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COMMUNITY CORNER
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Cardiovascular biomarker questioned p998
doi:10.1038/nm0909-998
http://links.ealert.nature.com/ctt?kn=50&m=33991969&r=MTc2NTQyNDEzOQS2&b=2&j=NTc1ODczNjYS1&mt=1&rt=0
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BETWEEN BEDSIDE AND BENCH
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A safer stem cell
Before stem cell therapies become mainstream, several hurdles must be overcome. One challenge is developing air-tight approaches to assure that stem cell transplantation does not give rise to tumors. Another is finding safe ways to induce pluripotency in adult stem cells, which can then be used for transplantation. In Bedside to Bench, Evan Snyder and Rahul Jandial discuss the risks of tumorigenesis in stem cell therapies, and, in Bench to Bedside, Laura Clarke and Derek van der Kooy examine new ways to induce pluripotency.
A safer stem cell: on guard against cancer pp999 - 1001
Rahul Jandial and Evan Y Snyder
doi:10.1038/nm0909-999
http://links.ealert.nature.com/ctt?kn=52&m=33991969&r=MTc2NTQyNDEzOQS2&b=2&j=NTc1ODczNjYS1&mt=1&rt=0
A safer stem cell: inducing pluripotency pp1001 - 1002
Laura Clarke and Derek van der Kooy
doi:10.1038/nm0909-1001
http://links.ealert.nature.com/ctt?kn=54&m=33991969&r=MTc2NTQyNDEzOQS2&b=2&j=NTc1ODczNjYS1&mt=1&rt=0
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RESEARCH HIGHLIGHTS
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Research Highlights pp1004 - 1005
doi:10.1038/nm0909-1004
http://links.ealert.nature.com/ctt?kn=56&m=33991969&r=MTc2NTQyNDEzOQS2&b=2&j=NTc1ODczNjYS1&mt=1&rt=0
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COMMENTARY
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The advancement of translational medicine-from regional challenges to global solutions pp1006 - 1009
Salvatore Albani and Berent Prakken
doi:10.1038/nm0909-1006
http://links.ealert.nature.com/ctt?kn=36&m=33991969&r=MTc2NTQyNDEzOQS2&b=2&j=NTc1ODczNjYS1&mt=1&rt=0
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PERSPECTIVE
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Cancer stem cells: mirage or reality? pp1010 - 1012
Piyush B Gupta, Christine L Chaffer and Robert A Weinberg
doi:10.1038/nm0909-1010
Abstract: http://links.ealert.nature.com/ctt?kn=178&m=33991969&r=MTc2NTQyNDEzOQS2&b=2&j=NTc1ODczNjYS1&mt=1&rt=0
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=========================== ADVERTISEMENT ===========================
UCSD Clinical and Translational Research Institute and Nature Medicine present:
Frontiers of Clinical Investigation Symposium
Metabolism 2009: From Bench to Bedside
October 8-10, 2009
La Jolla, California, USA
The theme for this year's symposium explores innovative approaches to bridge laboratory investigation to clinical research in metabolism.
Abstract Submission: Deadline: August 21, 2009
Early Bird Deadline: September 8, 2009
For more information visit: www.nature.com/natureconferences/ctri2009
anatureconference
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BRIEF COMMUNICATION
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Involvement of interleukin-21 in the epidermal hyperplasia of psoriasis pp1013 - 1015
Giovanni Monteleone and his colleagues show that the T cell-derived cytokine interleukin-21 is a new potential therapeutic target for psoriasis. Interleukin-21 seems to act directly on keratinocytes, stimulating them to proliferate and causing epidermal hyperplasia.
Roberta Caruso et al.
doi:10.1038/nm.1995
Abstract: http://links.ealert.nature.com/ctt?kn=169&m=33991969&r=MTc2NTQyNDEzOQS2&b=2&j=NTc1ODczNjYS1&mt=1&rt=0
Article: http://links.ealert.nature.com/ctt?kn=45&m=33991969&r=MTc2NTQyNDEzOQS2&b=2&j=NTc1ODczNjYS1&mt=1&rt=0
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ARTICLES
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A human colonic commensal promotes colon tumorigenesis via activation of T helper type 17 T cell responses pp1016 - 1022
Enterotoxigenic Bacteroides fragilis, a bacterium from the intestinal flora, may promote colon tumor formation through a pathway that involves Stat3 expression and T helper type 17 immune responses.
Shaoguang Wu et al.
doi:10.1038/nm.2015
Abstract: http://links.ealert.nature.com/ctt?kn=170&m=33991969&r=MTc2NTQyNDEzOQS2&b=2&j=NTc1ODczNjYS1&mt=1&rt=0
Article: http://links.ealert.nature.com/ctt?kn=163&m=33991969&r=MTc2NTQyNDEzOQS2&b=2&j=NTc1ODczNjYS1&mt=1&rt=0
Alternatively spliced vascular endothelial growth factor receptor-2 is an essential endogenous inhibitor of lymphatic vessel growth pp1023 - 1030
Although endogenous inhibitors of blood vessel growth have been studied extensively, specific inhibitors of lymphatic vessel growth have not been identified. Albuquerque et al. now identify truncated, secreted versions of mouse and human VEGFR-2 receptors generated by alternative splicing. The mouse protein acts as an endogenous inhibitor of lymphatic vessel growth in the cornea and skin, and its administration had therapeutic effects in mouse models of corneal injury and transplantation.
Romulo J C Albuquerque et al.
doi:10.1038/nm.2018
Abstract: http://links.ealert.nature.com/ctt?kn=171&m=33991969&r=MTc2NTQyNDEzOQS2&b=2&j=NTc1ODczNjYS1&mt=1&rt=0
Article: http://links.ealert.nature.com/ctt?kn=5&m=33991969&r=MTc2NTQyNDEzOQS2&b=2&j=NTc1ODczNjYS1&mt=1&rt=0
Pericyte contraction induced by oxidative-nitrative stress impairs capillary reflow despite successful opening of an occluded cerebral artery pp1031 - 1037
Ischemia causes pericytes on brain microvessels to contract, obstructing erythrocyte transit even after blood flow is restored. This contraction, which depends on the production of oxygen and nitrogen radicals, represents a novel pathophysiological mechanism in stroke.
Muge Yemisci et al.
doi:10.1038/nm.2022
Abstract: http://links.ealert.nature.com/ctt?kn=76&m=33991969&r=MTc2NTQyNDEzOQS2&b=2&j=NTc1ODczNjYS1&mt=1&rt=0
Article: http://links.ealert.nature.com/ctt?kn=157&m=33991969&r=MTc2NTQyNDEzOQS2&b=2&j=NTc1ODczNjYS1&mt=1&rt=0
A granulocyte-macrophage colony-stimulating factor and interleukin-15 fusokine induces a regulatory B cell population with immune suppressive properties pp1038 - 1045
Suppression of the immune system could block autoimmune disease pathogenesis. Here Jacques Galipeau and his colleagues report that a fusion protein of two cytokines can induce immunosuppressive regulatory B cells. Transferring these cells into a mouse model of multiple sclerosis reduces disease in the mice.
Moutih Rafei et al.
doi:10.1038/nm.2003
Abstract: http://links.ealert.nature.com/ctt?kn=83&m=33991969&r=MTc2NTQyNDEzOQS2&b=2&j=NTc1ODczNjYS1&mt=1&rt=0
Article: http://links.ealert.nature.com/ctt?kn=151&m=33991969&r=MTc2NTQyNDEzOQS2&b=2&j=NTc1ODczNjYS1&mt=1&rt=0
Impaired Wnt-B-catenin signaling disrupts adult renal homeostasis and leads to cystic kidney ciliopathy pp1046 - 1054
Canonical Wnt signaling is known to be crucial in embryonic organ development. Joseph Gleeson and his colleagues now report that it is also important in the adult homeostasis of the kidney, especially after injury, and that disruption of this signaling pathway results in cystic kidney disease.
Madeline A Lancaster et al.
doi:10.1038/nm.2010
Abstract: http://links.ealert.nature.com/ctt?kn=84&m=33991969&r=MTc2NTQyNDEzOQS2&b=2&j=NTc1ODczNjYS1&mt=1&rt=0
Article: http://links.ealert.nature.com/ctt?kn=145&m=33991969&r=MTc2NTQyNDEzOQS2&b=2&j=NTc1ODczNjYS1&mt=1&rt=0
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LETTERS
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Primary cilia can both mediate and suppress Hedgehog pathway-dependent tumorigenesis pp1055 - 1061
These two studies show that primary cilia can either mediate or suppress tumorigenesis in models of basal cell carcinoma and medulloblastoma, respectively, depending on the nature of the initial oncogenic event (pages 994-996) and (pages 1062-1065).
Sunny Y Wong et al.
doi:10.1038/nm.2011
Abstract: http://links.ealert.nature.com/ctt?kn=85&m=33991969&r=MTc2NTQyNDEzOQS2&b=2&j=NTc1ODczNjYS1&mt=1&rt=0
Article: http://links.ealert.nature.com/ctt?kn=2&m=33991969&r=MTc2NTQyNDEzOQS2&b=2&j=NTc1ODczNjYS1&mt=1&rt=0
Dual and opposing roles of primary cilia in medulloblastoma development pp1062 - 1065
These two studies show that primary cilia can either mediate or suppress tumorigenesis in models of basal cell carcinoma and medulloblastoma, respectively, depending on the nature of the initial oncogenic event (pages 994-996) and (pages 1055-1061).
Young-Goo Han et al.
doi:10.1038/nm.2020
Abstract: http://links.ealert.nature.com/ctt?kn=86&m=33991969&r=MTc2NTQyNDEzOQS2&b=2&j=NTc1ODczNjYS1&mt=1&rt=0
Article: http://links.ealert.nature.com/ctt?kn=59&m=33991969&r=MTc2NTQyNDEzOQS2&b=2&j=NTc1ODczNjYS1&mt=1&rt=0
Interferon regulatory factor-8 regulates bone metabolism by suppressing osteoclastogenesis pp1066 - 1071
Dysregulation of osteoclasts, the cells that chew up bone, can lead to severe bone loss. Although many positive regulators of the differentiation of this cell type have been identified, few negative regulators have. Now, Masamichi Takami and colleagues have identified IRF-8 as an inhibitor of osteoclast formation and explore its role in disease.
Baohong Zhao et al.
doi:10.1038/nm.2007
Abstract: http://links.ealert.nature.com/ctt?kn=77&m=33991969&r=MTc2NTQyNDEzOQS2&b=2&j=NTc1ODczNjYS1&mt=1&rt=0
Article: http://links.ealert.nature.com/ctt?kn=144&m=33991969&r=MTc2NTQyNDEzOQS2&b=2&j=NTc1ODczNjYS1&mt=1&rt=0
Syndecan-4 regulates ADAMTS-5 activation and cartilage breakdown in osteoarthritis pp1072 - 1076
The degenerative joint disease osteoarthritis is known to involve the activation of the protease ADAMTS-5. Now, Frank Echtermeyer and his colleagues have shown that the transmembrane proteoglycan syndecan-4 is responsible for this activation. They also show that genetic deletion of syndecan-4, or inhibition with a blocking antibody, reduces disease progression in a mouse model.
Frank Echtermeyer et al.
doi:10.1038/nm.1998
Abstract: http://links.ealert.nature.com/ctt?kn=78&m=33991969&r=MTc2NTQyNDEzOQS2&b=2&j=NTc1ODczNjYS1&mt=1&rt=0
Article: http://links.ealert.nature.com/ctt?kn=188&m=33991969&r=MTc2NTQyNDEzOQS2&b=2&j=NTc1ODczNjYS1&mt=1&rt=0
NADPH oxidase-4 mediates myofibroblast activation and fibrogenic responses to lung injury pp1077 - 1081
The mechanisms that lead to idiopathic pulmonary fibrosis, or lung scarring, is not clear. Victor Thannickal and his colleagues have now provided further insight by showing that induction of NOX4, an enzyme that creates reactive oxygen species, is required for the progression of the disease. Their findings suggest NOX4 as a potential target to treat this common ailment that currently has no proven treatment options.
Louise Hecker et al.
doi:10.1038/nm.2005
Abstract: http://links.ealert.nature.com/ctt?kn=79&m=33991969&r=MTc2NTQyNDEzOQS2&b=2&j=NTc1ODczNjYS1&mt=1&rt=0
Article: http://links.ealert.nature.com/ctt?kn=189&m=33991969&r=MTc2NTQyNDEzOQS2&b=2&j=NTc1ODczNjYS1&mt=1&rt=0
A crucial role for adipose tissue p53 in the regulation of insulin resistance pp1082 - 1087
A role for cell senescence and p53 in the development of insulin resistance (or prediabetes) has been obscure. Issei Komuro and colleagues now show that premature cell senescence occurs in the adipose tissue of obese mice and humans and that genetic deficiency of p53 is sufficient to prevent insulin resistance in mouse models of obesity, suggesting a new target to treat diabetes.
Tohru Minamino et al.
doi:10.1038/nm.2014
Abstract: http://links.ealert.nature.com/ctt?kn=81&m=33991969&r=MTc2NTQyNDEzOQS2&b=2&j=NTc1ODczNjYS1&mt=1&rt=0
Article: http://links.ealert.nature.com/ctt?kn=51&m=33991969&r=MTc2NTQyNDEzOQS2&b=2&j=NTc1ODczNjYS1&mt=1&rt=0
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TECHNICAL REPORT
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A rapid and efficient single-cell manipulation method for screening antigen-specific antibody-secreting cells from human peripheral blood pp1088 - 1092
Aishun Jin et al.
doi:10.1038/nm.1966
Abstract: http://links.ealert.nature.com/ctt?kn=70&m=33991969&r=MTc2NTQyNDEzOQS2&b=2&j=NTc1ODczNjYS1&mt=1&rt=0
Article: http://links.ealert.nature.com/ctt?kn=183&m=33991969&r=MTc2NTQyNDEzOQS2&b=2&j=NTc1ODczNjYS1&mt=1&rt=0
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ERRATUM
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Erratum: GOAT links dietary lipids with the endocrine control of energy balance p1093
Henriette Kirchner et al.
doi:10.1038/nm0909-1093a
http://links.ealert.nature.com/ctt?kn=173&m=33991969&r=MTc2NTQyNDEzOQS2&b=2&j=NTc1ODczNjYS1&mt=1&rt=0
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CORRIGENDUM
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Corrigendum: Aldosterone impairs vascular reactivity by decreasing glucose-6-phosphate dehydrogenase activity p1093
Jane A Leopold et al.
doi:10.1038/nm0909-1093b
http://links.ealert.nature.com/ctt?kn=175&m=33991969&r=MTc2NTQyNDEzOQS2&b=2&j=NTc1ODczNjYS1&mt=1&rt=0
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