March 2010 Volume 16 Number 3, pp 239 - 345
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Free download alert from Nature Reviews Immunology
Poster on Proximal tyrosine kinases that initiate T cell activation
T cells are central to a successful immune response. Proximal tyrosine kinases convert signals that are initiated by the recognition of antigen by the T cell receptor (TCR) into biochemical signals within the cell, resulting in the activation of T cell effector functions.
This Poster provides an overview of the regulatory mechanisms that control several proximal tyrosine kinases and highlights ways in which tyrosine kinases might be targeted for therapeutic purposes.
Download the poster for FREE
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NATURE MEDICINE PODCAST
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Bone up
We survey a bone-building drug for osteoporosis, rat models made to order and a new vaccine against Chikungunya virus.
Listen Now
http://links.ealert.nature.com/ctt?kn=16&m=34685205&r=MTc2NTQyNDEzOQS2&b=2&j=Njg2MzY4MTUS1&mt=1&rt=0
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EDITORIAL
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Peering into review p239
doi:10.1038/nm0310-239
The peer review process can be frustrating to researchers eager to get their work published. Changes to the process might be warranted-but only if they are based in fact, not conjecture.
http://links.ealert.nature.com/ctt?kn=128&m=34685205&r=MTc2NTQyNDEzOQS2&b=2&j=Njg2MzY4MTUS1&mt=1&rt=0
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NEWS
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Rare opportunities appear on the horizon to treat rare diseases p241
Christian Torres
doi:10.1038/nm0310-241
http://links.ealert.nature.com/ctt?kn=124&m=34685205&r=MTc2NTQyNDEzOQS2&b=2&j=Njg2MzY4MTUS1&mt=1&rt=0
In Haiti, collapsed AIDS clinics fret over new challenges p242
Elie Dolgin
doi:10.1038/nm0310-242
http://links.ealert.nature.com/ctt?kn=137&m=34685205&r=MTc2NTQyNDEzOQS2&b=2&j=Njg2MzY4MTUS1&mt=1&rt=0
Obama's budget boosts biomedicine p243
doi:10.1038/nm0310-243a
http://links.ealert.nature.com/ctt?kn=133&m=34685205&r=MTc2NTQyNDEzOQS2&b=2&j=Njg2MzY4MTUS1&mt=1&rt=0
Vaccine funds will save lives p243
Cassandra Willyard
doi:10.1038/nm0310-243b
http://links.ealert.nature.com/ctt?kn=154&m=34685205&r=MTc2NTQyNDEzOQS2&b=2&j=Njg2MzY4MTUS1&mt=1&rt=0
Pharma spends big to buy influence p243
doi:10.1038/nm0310-243c
http://links.ealert.nature.com/ctt?kn=153&m=34685205&r=MTc2NTQyNDEzOQS2&b=2&j=Njg2MzY4MTUS1&mt=1&rt=0
FDA initiative may crack wall of secrecy p244
Charlotte Schubert
doi:10.1038/nm0310-244
http://links.ealert.nature.com/ctt?kn=158&m=34685205&r=MTc2NTQyNDEzOQS2&b=2&j=Njg2MzY4MTUS1&mt=1&rt=0
Patent disputes could trip up genome wide scans for disease p245
Brendan Borrell
doi:10.1038/nm0310-245a
http://links.ealert.nature.com/ctt?kn=156&m=34685205&r=MTc2NTQyNDEzOQS2&b=2&j=Njg2MzY4MTUS1&mt=1&rt=0
Industry's influence in biologics legislation examined p245
Elie Dolgin
doi:10.1038/nm0310-245b
http://links.ealert.nature.com/ctt?kn=37&m=34685205&r=MTc2NTQyNDEzOQS2&b=2&j=Njg2MzY4MTUS1&mt=1&rt=0
Patents draw new lines in the battle to commercialize stem cells p246
Elie Dolgin
doi:10.1038/nm0310-246
http://links.ealert.nature.com/ctt?kn=31&m=34685205&r=MTc2NTQyNDEzOQS2&b=2&j=Njg2MzY4MTUS1&mt=1&rt=0
New commissioner spells new direction for EU research funding p247
Lucas Laursen
doi:10.1038/nm0310-247a
http://links.ealert.nature.com/ctt?kn=33&m=34685205&r=MTc2NTQyNDEzOQS2&b=2&j=Njg2MzY4MTUS1&mt=1&rt=0
Researchers unite to improve Parkinson's drug discovery p247
Elie Dolgin
doi:10.1038/nm0310-247b
http://links.ealert.nature.com/ctt?kn=27&m=34685205&r=MTc2NTQyNDEzOQS2&b=2&j=Njg2MzY4MTUS1&mt=1&rt=0
State of denial p248
Megan Scudellari
doi:10.1038/nm0310-248a
http://links.ealert.nature.com/ctt?kn=29&m=34685205&r=MTc2NTQyNDEzOQS2&b=2&j=Njg2MzY4MTUS1&mt=1&rt=0
A timeline of the Wakefield retraction p248
doi:10.1038/nm0310-248b
http://links.ealert.nature.com/ctt?kn=17&m=34685205&r=MTc2NTQyNDEzOQS2&b=2&j=Njg2MzY4MTUS1&mt=1&rt=0
Electronic records pose dilemma in developing countries p249
Cassandra Willyard
doi:10.1038/nm0310-249a
http://links.ealert.nature.com/ctt?kn=1&m=34685205&r=MTc2NTQyNDEzOQS2&b=2&j=Njg2MzY4MTUS1&mt=1&rt=0
Comparative push concerns minorities p249
Christian Torres
doi:10.1038/nm0310-249b
http://links.ealert.nature.com/ctt?kn=11&m=34685205&r=MTc2NTQyNDEzOQS2&b=2&j=Njg2MzY4MTUS1&mt=1&rt=0
Focus on Electronic Health Records
'HIPAA2' legislation means more delicate handling of data p250
Mike May
doi:10.1038/nm0310-250a
http://links.ealert.nature.com/ctt?kn=8&m=34685205&r=MTc2NTQyNDEzOQS2&b=2&j=Njg2MzY4MTUS1&mt=1&rt=0
Focus on Electronic Health Records
Grassley probes health care technology p250
Mike May
doi:10.1038/nm0310-250b
http://links.ealert.nature.com/ctt?kn=6&m=34685205&r=MTc2NTQyNDEzOQS2&b=2&j=Njg2MzY4MTUS1&mt=1&rt=0
Focus on Electronic Health Records
Pharma sets its sights on secondary data use p251
Christian Torres
doi:10.1038/nm0310-251a
http://links.ealert.nature.com/ctt?kn=3&m=34685205&r=MTc2NTQyNDEzOQS2&b=2&j=Njg2MzY4MTUS1&mt=1&rt=0
Focus on Electronic Health Records
Small practices find little incentive to go electronic p251
Christian Torres
doi:10.1038/nm0310-251b
http://links.ealert.nature.com/ctt?kn=57&m=34685205&r=MTc2NTQyNDEzOQS2&b=2&j=Njg2MzY4MTUS1&mt=1&rt=0
News in brief pp252 - 253
doi:10.1038/nm0310-252
http://links.ealert.nature.com/ctt?kn=59&m=34685205&r=MTc2NTQyNDEzOQS2&b=2&j=Njg2MzY4MTUS1&mt=1&rt=0
The knockout rat pack pp254 - 257
Elie Dolgin
doi:10.1038/nm0310-254
The rat is the preferred model organism in many fields of biomedicine, such as toxicology testing. But when it comes to disease models, rats have been upstaged by mice, which traditionally were far easier to genetically engineer. Elie Dolgin follows the tale of the researchers who are bringing the rat back into the race.
http://links.ealert.nature.com/ctt?kn=61&m=34685205&r=MTc2NTQyNDEzOQS2&b=2&j=Njg2MzY4MTUS1&mt=1&rt=0
An apt approach pp258 - 260
Alan Dove
doi:10.1038/nm0310-258
A new microbicide built from two types of RNA has shown promise against HIV in lab experiments, but moving it toward becoming a marketable product is proving difficult. Alan Dove investigates what's interfering with this novel therapeutic RNA strategy.
http://links.ealert.nature.com/ctt?kn=63&m=34685205&r=MTc2NTQyNDEzOQS2&b=2&j=Njg2MzY4MTUS1&mt=1&rt=0
Straight talk with...Shlomo Yanai p261
Haim Watzman
doi:10.1038/nm0310-261
Abstract: http://links.ealert.nature.com/ctt?kn=73&m=34685205&r=MTc2NTQyNDEzOQS2&b=2&j=Njg2MzY4MTUS1&mt=1&rt=0
Article: http://links.ealert.nature.com/ctt?kn=64&m=34685205&r=MTc2NTQyNDEzOQS2&b=2&j=Njg2MzY4MTUS1&mt=1&rt=0
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BOOK REVIEW
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Globalizing pharmaceutical trials p262
George J Annas reviews When Experiments Travel: Clinical Trials and the Global Search for Human Subjects by Adriana Petryna
doi:10.1038/nm0310-262
http://links.ealert.nature.com/ctt?kn=40&m=34685205&r=MTc2NTQyNDEzOQS2&b=2&j=Njg2MzY4MTUS1&mt=1&rt=0
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NEWS AND VIEWS
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A sweet target for innate immunity pp263 - 264
Fu-Tong Liu and Charles L Bevins
doi:10.1038/nm0310-263
Galectins are carbohydrate-binding proteins with diverse activities, but there is no unifying picture of their primary physiological role. Galectins now emerge as autonomous bacteria-killing agents (pages 295-301), unexpected findings that may point to a principal role of these proteins in innate immunity.
http://links.ealert.nature.com/ctt?kn=46&m=34685205&r=MTc2NTQyNDEzOQS2&b=2&j=Njg2MzY4MTUS1&mt=1&rt=0
Rebuilding Humpty Dumpty with a serotonin inhibitor pp264 - 265
Ego Seeman
doi:10.1038/nm0310-264
Serotonin produced in the gut reduces the formation of bone. This biology is now harnessed with an orally available inhibitor of gut serotonin synthesis (pages 308-312). The inhibitor promotes bone formation in rodents and points the way to the development of much-needed bone-building drugs.
http://links.ealert.nature.com/ctt?kn=42&m=34685205&r=MTc2NTQyNDEzOQS2&b=2&j=Njg2MzY4MTUS1&mt=1&rt=0
Ido brings down the pressure in systemic inflammation pp265 - 267
Franz Hofmann
doi:10.1038/nm0310-265
Systemic inflammation results in a life-threatening drop in blood pressure. Targeting known players of blood pressure regulation has so far failed to improve outcomes for individuals with sepsis. But a study points to a regulatory pathway involving the amino acid metabolite kynurenine that may provide new avenues for therapies (pages 279-285).
http://links.ealert.nature.com/ctt?kn=47&m=34685205&r=MTc2NTQyNDEzOQS2&b=2&j=Njg2MzY4MTUS1&mt=1&rt=0
Lipids control mucus production in cystic fibrosis pp267 - 268
Erich Gulbins
doi:10.1038/nm0310-267
Altered lipid metabolism underlies the production of excess mucus in a mouse model of cystic fibrosis (313-318). The findings point to the nuclear receptor peroxisome proliferator-activated receptor-gamma (PPAR-gamma) as a potential therapeutic target in this disease.
http://links.ealert.nature.com/ctt?kn=139&m=34685205&r=MTc2NTQyNDEzOQS2&b=2&j=Njg2MzY4MTUS1&mt=1&rt=0
HIV vaccines: mosaic approach to virus diversity pp268 - 270
Lawrence Corey and M Juliana McElrath
doi:10.1038/nm0310-268
The extraordinary diversity of HIV is a major barrier in the path of developing a vaccine. One way forward may be mosaic antigens-biometrically designed genes that maximize overlap between sequences used in the vaccine and circulating HIV-1 strains worldwide (pages 319-323 and 324-328).
http://links.ealert.nature.com/ctt?kn=136&m=34685205&r=MTc2NTQyNDEzOQS2&b=2&j=Njg2MzY4MTUS1&mt=1&rt=0
Spasticity: a switch from inhibition to excitation pp270 - 271
V Reggie Edgerton and Roland R Roy
doi:10.1038/nm0310-270
The involuntary muscle spasms that occur as a result of neuromotor disorders and spinal cord injury can have dangerous consequences for affected individuals. New findings shed light on one mechanism contributing to spasticity: limited chloride transport in motoneurons (pages 302-307).
http://links.ealert.nature.com/ctt?kn=127&m=34685205&r=MTc2NTQyNDEzOQS2&b=2&j=Njg2MzY4MTUS1&mt=1&rt=0
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COMMUNITY CORNER
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New drugs may improve, complicate treatment for multiple sclerosis p272
doi:10.1038/nm0310-272
http://links.ealert.nature.com/ctt?kn=101&m=34685205&r=MTc2NTQyNDEzOQS2&b=2&j=Njg2MzY4MTUS1&mt=1&rt=0
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BETWEEN BEDSIDE AND BENCH
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Asthma and allergy
Thinking about how asthma and allergic diseases arise is undergoing several shifts. In 'Bedside to Bench', Clare M. Lloyd and Sejal Saglani examine how recent human studies are putting the focus on the epithelium as a major contributor to asthma. The findings shift the emphasis away from the T helper type 2 immune response, and call into question the utility of current animal models of the disease. Although asthma and other allergic disorders are known to have origins in infancy, some researchers are looking even earlier, to effects in utero and before conception. In 'Bench to Bedside', Catherine Hawrylowicz and Kimuli Ryanna highlight animal studies that outline some of the effects of the maternal environment, and they examine the potential implications for prevention of disease.
Asthma and allergy: The emerging epithelium pp273 - 274
Clare M Lloyd and Sejal Saglani
doi:10.1038/nm0310-273
http://links.ealert.nature.com/ctt?kn=104&m=34685205&r=MTc2NTQyNDEzOQS2&b=2&j=Njg2MzY4MTUS1&mt=1&rt=0
Asthma and allergy: The early beginnings pp274 - 275
Catherine Hawrylowicz and Kimuli Ryanna
doi:10.1038/nm0310-274
http://links.ealert.nature.com/ctt?kn=93&m=34685205&r=MTc2NTQyNDEzOQS2&b=2&j=Njg2MzY4MTUS1&mt=1&rt=0
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RESEARCH HIGHLIGHTS
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Research Highlights pp276 - 277
doi:10.1038/nm0310-276
http://links.ealert.nature.com/ctt?kn=98&m=34685205&r=MTc2NTQyNDEzOQS2&b=2&j=Njg2MzY4MTUS1&mt=1&rt=0
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ARTICLES
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Kynurenine is an endothelium-derived relaxing factor produced during inflammation pp279 - 285
Yutang Wang et al.
doi:10.1038/nm.2092
Kynurenine, a metabolite produced by the action of the enzyme indoleamine 2,3-dioxygenase on tryptophan, accumulates under inflammatory conditions and has immunomodulatory effects. This study by Yutang Wang et al. describes a new function for kynurenine as an endogenous vasodilator under conditions of systemic inflammation, such as malaria infection and endotoxemia in mice, and provides insight into the molecular mechanisms involved (pages 265-267).
Abstract: http://links.ealert.nature.com/ctt?kn=75&m=34685205&r=MTc2NTQyNDEzOQS2&b=2&j=Njg2MzY4MTUS1&mt=1&rt=0
Article: http://links.ealert.nature.com/ctt?kn=145&m=34685205&r=MTc2NTQyNDEzOQS2&b=2&j=Njg2MzY4MTUS1&mt=1&rt=0
An oncogene-tumor suppressor cascade drives metastatic prostate cancer by coordinately activating Ras and nuclear factor-kappaB pp286 - 294
Junxia Min et al.
doi:10.1038/nm.2100
Metastasis is a fatal complication of prostate cancer, but its mechanisms remain largely unknown. In this report, the authors identify a signaling pathway commonly deregulated in human prostate cancer and describe how it can foster both primary growth and metastatic tumor progression. Epigenetic silencing of the RasGAP DAB2IP by EZH2 overexpression results in aberrant activation of Ras signaling, but also of NF-kappaB. These two events are mediated by different DAB2IP domains and have distinct roles in localized growth and distant dissemination.
Abstract: http://links.ealert.nature.com/ctt?kn=86&m=34685205&r=MTc2NTQyNDEzOQS2&b=2&j=Njg2MzY4MTUS1&mt=1&rt=0
Article: http://links.ealert.nature.com/ctt?kn=190&m=34685205&r=MTc2NTQyNDEzOQS2&b=2&j=Njg2MzY4MTUS1&mt=1&rt=0
Innate immune lectins kill bacteria expressing blood group antigen pp295 - 301
Sean R Stowell et al.
doi:10.1038/nm.2103
The expression of blood group antigens causes deletion of cells that generate self-specific antibodies to those antigens, but this deletion could limit adaptive immunity toward pathogens bearing cognate antigens. Two innate immune lectins, galectin-4 and galectin-8, are now reported to recognize and kill human blood group antigen-expressing bacteria.
Abstract: http://links.ealert.nature.com/ctt?kn=88&m=34685205&r=MTc2NTQyNDEzOQS2&b=2&j=Njg2MzY4MTUS1&mt=1&rt=0
Article: http://links.ealert.nature.com/ctt?kn=43&m=34685205&r=MTc2NTQyNDEzOQS2&b=2&j=Njg2MzY4MTUS1&mt=1&rt=0
Down-regulation of the potassium-chloride cotransporter KCC2 contributes to spasticity after spinal cord injury pp302 - 307
Pascale Boulenguez et al.
doi:10.1038/nm.2107
Muscle spasticity is a major problem for individuals with SCI. Now, Laurent Vinay and his colleagues report that downregulation of the potassium-chloride cotransporter in spinal cord motor neurons after SCI has a key role in the development of spasticity (pages 270-271).
Abstract: http://links.ealert.nature.com/ctt?kn=84&m=34685205&r=MTc2NTQyNDEzOQS2&b=2&j=Njg2MzY4MTUS1&mt=1&rt=0
Article: http://links.ealert.nature.com/ctt?kn=100&m=34685205&r=MTc2NTQyNDEzOQS2&b=2&j=Njg2MzY4MTUS1&mt=1&rt=0
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LETTERS
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Pharmacological inhibition of gut-derived serotonin synthesis is a potential bone anabolic treatment for osteoporosis pp308 - 312
Vijay K Yadav et al.
doi:10.1038/nm.2098
Osteoporosis results from misregulation of bone catabolism and bone anabolism, resulting in severe bone loss. Most current therapies act by decreasing bone catabolism, but targeting bone anabolism is more desired, because once bone is lost, it is difficult to replace. In a new report by Gerard Karsenty and his colleagues, they show that orally delivered pharmacological targeting of serotonin synthesis in the gut is sufficient to increase bone anabolism and thus restore lost bone in rat and mouse models of well-established osteoporosis (pages 264-265).
Abstract: http://links.ealert.nature.com/ctt?kn=85&m=34685205&r=MTc2NTQyNDEzOQS2&b=2&j=Njg2MzY4MTUS1&mt=1&rt=0
Article: http://links.ealert.nature.com/ctt?kn=48&m=34685205&r=MTc2NTQyNDEzOQS2&b=2&j=Njg2MzY4MTUS1&mt=1&rt=0
Pharmacological correction of a defect in PPAR-gamma signaling ameliorates disease severity in Cftr-deficient mice pp313 - 318
Gregory S Harmon et al.
doi:10.1038/nm.2101
Defects in the ion transporter CFTR result in cystic fibrosis, which is marked by excessive mucous buildup in the lungs and colon and premature death. Christopher Glass and his colleagues now show that these aspects of the disease are associated with defects in PPAR-gamma signaling in epithelial cells and that a synthetic agonist of this nuclear receptor is sufficient to partially normalize signaling and improve survival of a mouse model (pages 267-268).
Abstract: http://links.ealert.nature.com/ctt?kn=82&m=34685205&r=MTc2NTQyNDEzOQS2&b=2&j=Njg2MzY4MTUS1&mt=1&rt=0
Article: http://links.ealert.nature.com/ctt?kn=134&m=34685205&r=MTc2NTQyNDEzOQS2&b=2&j=Njg2MzY4MTUS1&mt=1&rt=0
Mosaic HIV-1 vaccines expand the breadth and depth of cellular immune responses in rhesus monkeys pp319 - 323
Dan H Barouch et al.
doi:10.1038/nm.2089
Vaccine design is challenging when the infectious agent is genetically diverse. Polyvalent 'mosaic' antigens might be used to address this challenge, and these two studies show promising results in monkeys infected with HIV-1 (pages 268-270 and 324-328).
Abstract: http://links.ealert.nature.com/ctt?kn=83&m=34685205&r=MTc2NTQyNDEzOQS2&b=2&j=Njg2MzY4MTUS1&mt=1&rt=0
Article: http://links.ealert.nature.com/ctt?kn=132&m=34685205&r=MTc2NTQyNDEzOQS2&b=2&j=Njg2MzY4MTUS1&mt=1&rt=0
Mosaic vaccines elicit CD8+ T lymphocyte responses that confer enhanced immune coverage of diverse HIV strains in monkeys pp324 - 328
Sampa Santra et al.
doi:10.1038/nm.2108
Vaccine design is challenging when the infectious agent is genetically diverse. Polyvalent 'mosaic' antigens might be used to address this challenge, and these two studies show promising results in monkeys infected with HIV-1 (pages 268-270 and pages 319-323).
Abstract: http://links.ealert.nature.com/ctt?kn=80&m=34685205&r=MTc2NTQyNDEzOQS2&b=2&j=Njg2MzY4MTUS1&mt=1&rt=0
Article: http://links.ealert.nature.com/ctt?kn=125&m=34685205&r=MTc2NTQyNDEzOQS2&b=2&j=Njg2MzY4MTUS1&mt=1&rt=0
Concerted action of cellular JNK and Pin1 restricts HIV-1 genome integration to activated CD4+ T lymphocytes pp329 - 333
Lara Manganaro et al.
doi:10.1038/nm.2102
The concerted action of JNK and Pin1 on viral integrase regulate permissiveness of activated CD4+ T cells to HIV-1 infection, whereas lack of these modifications restricts viral infection in nonactivated lymphocytes.
Abstract: http://links.ealert.nature.com/ctt?kn=81&m=34685205&r=MTc2NTQyNDEzOQS2&b=2&j=Njg2MzY4MTUS1&mt=1&rt=0
Article: http://links.ealert.nature.com/ctt?kn=160&m=34685205&r=MTc2NTQyNDEzOQS2&b=2&j=Njg2MzY4MTUS1&mt=1&rt=0
A virus-like particle vaccine for epidemic Chikungunya virus protects nonhuman primates against infection pp334 - 338
Wataru Akahata et al.
doi:10.1038/nm.2105
Chikungunya virus (CHIKV) is an emerging infectious agent that can cause severe disease in humans and against which there is presently no vaccine. Akahata et al. now describe their development of a virus-like particle (VLP) vaccine that elicits neutralizing antibodies against CHIKV and can protect nonhuman primates from infection. Their VLP-based approach may facilitate development of a CHIKV vaccine for human use.
Abstract: http://links.ealert.nature.com/ctt?kn=72&m=34685205&r=MTc2NTQyNDEzOQS2&b=2&j=Njg2MzY4MTUS1&mt=1&rt=0
Article: http://links.ealert.nature.com/ctt?kn=118&m=34685205&r=MTc2NTQyNDEzOQS2&b=2&j=Njg2MzY4MTUS1&mt=1&rt=0
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TECHNICAL REPORT
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Development of replication-defective lymphocytic choriomeningitis virus vectors for the induction of potent CD8+ T cell immunity pp339 - 345
Lukas Flatz et al.
doi:10.1038/nm.2104
Abstract: http://links.ealert.nature.com/ctt?kn=71&m=34685205&r=MTc2NTQyNDEzOQS2&b=2&j=Njg2MzY4MTUS1&mt=1&rt=0
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