March 2009 Volume 15 Number 3, pp 221 - 344
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15 Evolutionary Gems
As the concepts and realities of Darwinian evolution are still challenged, albeit rarely by biologists, Nature provides a succinct briefing on why evolution by natural selection is an
empirically validated principle useful for people to have to hand. We offer here 15 examples from over the past decade or so to illustrate the breadth, depth and power of evolutionary thinking.
Access this resource from Nature, for those wishing to spread awareness of evidence for evolution by natural selection FREE online today!
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NATURE MEDICINE PODCAST
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Putty in your brain
The podcast reviews recent headlines in biomedicine and takes a close look at treatments targeting brain cells known as glia.
http://links.ealert.nature.com/ctt?kn=83&m=31848430&r=MTc2NTQyNDEzOQS2&b=2&j=NDYzMzE3ODYS1&mt=1&rt=0
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EDITORIAL
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Outsourcing safety pp221 - 222
With the global outsourcing of domestic drug manufacturing, the need to ensure the quality and safety of medical products has never been greater. But recent events show that the US Food and Drug Administration (FDA) is not up to the task.
doi:10.1038/nm0309-221
http://links.ealert.nature.com/ctt?kn=30&m=31848430&r=MTc2NTQyNDEzOQS2&b=2&j=NDYzMzE3ODYS1&mt=1&rt=0
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NEWS
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US drug agency blunts supply of marijuana for research p223
Arran Frood
doi:10.1038/nm0309-223
http://links.ealert.nature.com/ctt?kn=144&m=31848430&r=MTc2NTQyNDEzOQS2&b=2&j=NDYzMzE3ODYS1&mt=1&rt=0
US stem cell climate improves, raising concerns elsewhere p224
Nayanah Siva
doi:10.1038/nm0309-224a
http://links.ealert.nature.com/ctt?kn=111&m=31848430&r=MTc2NTQyNDEzOQS2&b=2&j=NDYzMzE3ODYS1&mt=1&rt=0
Tanks pose possible dengue threat p224
Simon Grose
doi:10.1038/nm0309-224b
http://links.ealert.nature.com/ctt?kn=138&m=31848430&r=MTc2NTQyNDEzOQS2&b=2&j=NDYzMzE3ODYS1&mt=1&rt=0
Rare nature of mushroom poisoning means drug trials rarer still p225
Amy Coombs
doi:10.1038/nm0309-225a
http://links.ealert.nature.com/ctt?kn=56&m=31848430&r=MTc2NTQyNDEzOQS2&b=2&j=NDYzMzE3ODYS1&mt=1&rt=0
Independent working group puts genetic tests under the microscope p225
Stu Hutson
doi:10.1038/nm0309-225b
http://links.ealert.nature.com/ctt?kn=61&m=31848430&r=MTc2NTQyNDEzOQS2&b=2&j=NDYzMzE3ODYS1&mt=1&rt=0
Pilot projects aim to ease access to clinical data p226
Kirsten Dorans
doi:10.1038/nm0309-226a
http://links.ealert.nature.com/ctt?kn=45&m=31848430&r=MTc2NTQyNDEzOQS2&b=2&j=NDYzMzE3ODYS1&mt=1&rt=0
Pfizer to disclose financial ties p226
Kirsten Dorans
doi:10.1038/nm0309-226b
http://links.ealert.nature.com/ctt?kn=89&m=31848430&r=MTc2NTQyNDEzOQS2&b=2&j=NDYzMzE3ODYS1&mt=1&rt=0
Survey gauges dual-use attitudes p226
Kirsten Dorans
doi:10.1038/nm0309-226c
http://links.ealert.nature.com/ctt?kn=65&m=31848430&r=MTc2NTQyNDEzOQS2&b=2&j=NDYzMzE3ODYS1&mt=1&rt=0
Royal Society urges integration of human and veterinary medicine p227
Kirsten Dorans
doi:10.1038/nm0309-227a
http://links.ealert.nature.com/ctt?kn=33&m=31848430&r=MTc2NTQyNDEzOQS2&b=2&j=NDYzMzE3ODYS1&mt=1&rt=0
Millions put toward making polio history p227
Kirsten Dorans
doi:10.1038/nm0309-227b
http://links.ealert.nature.com/ctt?kn=75&m=31848430&r=MTc2NTQyNDEzOQS2&b=2&j=NDYzMzE3ODYS1&mt=1&rt=0
News in brief pp228 - 229
doi:10.1038/nm0309-228
http://links.ealert.nature.com/ctt?kn=109&m=31848430&r=MTc2NTQyNDEzOQS2&b=2&j=NDYzMzE3ODYS1&mt=1&rt=0
Straight talk with...Mac Cowell and Jason Bobe pp230 - 231
Prashant Nair
doi:10.1038/nm0309-230
Abstract: http://links.ealert.nature.com/ctt?kn=17&m=31848430&r=MTc2NTQyNDEzOQS2&b=2&j=NDYzMzE3ODYS1&mt=1&rt=0
Article: http://links.ealert.nature.com/ctt?kn=128&m=31848430&r=MTc2NTQyNDEzOQS2&b=2&j=NDYzMzE3ODYS1&mt=1&rt=0
Three's company pp232 - 235
For many years, textbooks portrayed nerve communication as a straightforward process in which a signal simply hopped from one cell to the next. This traditional view also cast cells known as glia as passive bystanders to the signaling action between neurons. But scientists increasingly regard glia as influential third players in the space where signals pass between neurons, a space they have termed the 'tripartite synapse'. On the basis of this concept, some have begun to study the involvement of glia in nervous system disorders and to develop therapeutic compounds that target these cells. David Gruber reports.
David F. Gruber
doi:10.1038/nm0309-232
http://links.ealert.nature.com/ctt?kn=4&m=31848430&r=MTc2NTQyNDEzOQS2&b=2&j=NDYzMzE3ODYS1&mt=1&rt=0
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CORRESPONDENCE
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Stromal signature identifies basal breast cancers pp237 - 238
Kristian Wennmalm, Arne Ostman and Jonas Bergh
doi:10.1038/nm0309-237
http://links.ealert.nature.com/ctt?kn=58&m=31848430&r=MTc2NTQyNDEzOQS2&b=2&j=NDYzMzE3ODYS1&mt=1&rt=0
Stromal signature identifies basal breast cancers p238
Greg Finak, Nicholas Bertos, Michael Hallett and Morag Park
doi:10.1038/nm0309-238a
http://links.ealert.nature.com/ctt?kn=120&m=31848430&r=MTc2NTQyNDEzOQS2&b=2&j=NDYzMzE3ODYS1&mt=1&rt=0
The preimplantation embryo and Jewish law p238
Arthur I. Eidelman and Mordechai Halperin
doi:10.1038/nm0309-238b
http://links.ealert.nature.com/ctt?kn=24&m=31848430&r=MTc2NTQyNDEzOQS2&b=2&j=NDYzMzE3ODYS1&mt=1&rt=0
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BOOK REVIEW
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The boundaries of medicine p241
Dave E Marcotte reviews Comfortably Numb: How Psychiatry is Medicating a Nation by Charles Barber
doi:10.1038/nm0309-241
http://links.ealert.nature.com/ctt?kn=110&m=31848430&r=MTc2NTQyNDEzOQS2&b=2&j=NDYzMzE3ODYS1&mt=1&rt=0
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NEWS AND VIEWS
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NO may prompt calcium leakage in dystrophic muscle pp243 - 244
A remote, downstream event in the pathology of muscular dystrophy may have a key role in the disease (pages 325-330). It seems that induction of nitric oxide synthase causes calcium to leak inside the cell through ryanodine receptors. The findings provide new options for therapeutic interventions.
James G Tidball and S Armando Villalta
doi:10.1038/nm0309-243
http://links.ealert.nature.com/ctt?kn=54&m=31848430&r=MTc2NTQyNDEzOQS2&b=2&j=NDYzMzE3ODYS1&mt=1&rt=0
Choosing the right memory T cell for HIV pp244 - 246
An experimental simian immunodeficiency virus vaccine boosts production of memory T cells at the site where the virus first contacts the body[mdash]in the mucosa (pages 293-299). The approach has the potential to result in more effective HIV vaccines than those currently under development.
Genoveffa Franchini
doi:10.1038/nm0309-244
http://links.ealert.nature.com/ctt?kn=141&m=31848430&r=MTc2NTQyNDEzOQS2&b=2&j=NDYzMzE3ODYS1&mt=1&rt=0
Oxygen sensor boosts growth factor signaling pp246 - 247
Activation of hypoxia-inducible factor, a molecule central to oxygen sensing, can promote the survival and growth of tumor cells. New experiments dissect a pathway behind this effect[mdash]upregulation of the epidermal growth factor receptor (pages 319-324).
Mien-Chie Hung, Gordon B Mills and Dihua Yu
doi:10.1038/nm0309-246
http://links.ealert.nature.com/ctt?kn=49&m=31848430&r=MTc2NTQyNDEzOQS2&b=2&j=NDYzMzE3ODYS1&mt=1&rt=0
Intolerant of glucose and gasping for oxygen pp247 - 249
Findings in knockout mice indicate that hypoxia-sensitive pathways modulate the glucose-sensing machinery of pancreatic beta cells. Conditions that mimic hypoxia severely impair glucose-stimulated insulin release.
Fiona M Gribble
doi:10.1038/nm0309-247
http://links.ealert.nature.com/ctt?kn=79&m=31848430&r=MTc2NTQyNDEzOQS2&b=2&j=NDYzMzE3ODYS1&mt=1&rt=0
When integrins fail to integrate pp249 - 250
Three studies implicate Kindlin-3, a molecule that mediates signaling through integrins, in a rare disorder characterized by spontaneous bleeding and susceptibility to infection (pages 300-305, 306-312 and 313-318).
Andres Hidalgo and Paul S Frenette
doi:10.1038/nm0309-249
http://links.ealert.nature.com/ctt?kn=21&m=31848430&r=MTc2NTQyNDEzOQS2&b=2&j=NDYzMzE3ODYS1&mt=1&rt=0
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COMMUNITY CORNER
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Moving closer to a mouse model for hepatitis C p251
doi:10.1038/nm0309-251
http://links.ealert.nature.com/ctt?kn=51&m=31848430&r=MTc2NTQyNDEzOQS2&b=2&j=NDYzMzE3ODYS1&mt=1&rt=0
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BETWEEN BEDSIDE AND BENCH
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Getting a handle on Huntington's disease
Inherited neurodegenerative conditions such as Huntington's disease have proximal causes (a defective gene) and downstream causes (pathological events caused by that gene). Albert R. La Spada examines efforts to target bad genes with gene knockdown approaches on the eve of a clinical trial designed to silence the causative gene in familial amyotrophic lateral sclerosis. Masahisa Katsuno, Hiroaki Adachi and Gen Sobue examine the possibility of targeting a potentially damaging downstream event in Huntington's disease[mdash]dysregulated cholesterol metabolism in the brain.
Getting a handle on Huntington's disease: silencing neurodegeneration pp252 - 253
Albert R La Spada
doi:10.1038/nm0309-252
http://links.ealert.nature.com/ctt?kn=59&m=31848430&r=MTc2NTQyNDEzOQS2&b=2&j=NDYzMzE3ODYS1&mt=1&rt=0
Getting a handle on Huntington's disease: the case for cholesterol pp253 - 254
Masahisa Katsuno, Hiroaki Adachi and Gen Sobue
doi:10.1038/nm0309-253
http://links.ealert.nature.com/ctt?kn=5&m=31848430&r=MTc2NTQyNDEzOQS2&b=2&j=NDYzMzE3ODYS1&mt=1&rt=0
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RESEARCH HIGHLIGHTS
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Research Highlights pp256 - 257
doi:10.1038/nm0309-256
http://links.ealert.nature.com/ctt?kn=74&m=31848430&r=MTc2NTQyNDEzOQS2&b=2&j=NDYzMzE3ODYS1&mt=1&rt=0
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ARTICLES
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Coordination of PGC-1[beta] and iron uptake in mitochondrial biogenesis and osteoclast activation pp259 - 266
Bone is resorbed by osteoclasts, and too much activity by these cells leads to disease, such as osteoporosis. Here Kyoji Ikeda and colleagues show that the combined action of iron uptake and a key transcription factor involved in mitochondrial biogenesis are required for the proper functioning of these cells and that in cases of increased bone loss, iron chelation may be beneficial by inhibiting these cells.
Kiyo-aki Ishii et al.
doi:10.1038/nm.1910
Abstract: http://links.ealert.nature.com/ctt?kn=47&m=31848430&r=MTc2NTQyNDEzOQS2&b=2&j=NDYzMzE3ODYS1&mt=1&rt=0
Article: http://links.ealert.nature.com/ctt?kn=106&m=31848430&r=MTc2NTQyNDEzOQS2&b=2&j=NDYzMzE3ODYS1&mt=1&rt=0
Autophagy enhances the efficacy of BCG vaccine by increasing peptide presentation in mouse dendritic cells pp267 - 276
During autophagy, cytosolic proteins and damaged organelles are delivered via autophagosomes to lysosomes, where they are degraded before presentation at the cell surface. Agents that induce autophagy have previously been shown to boost antigen presentation in vitro. Here Chinnaswamy Jagannath and colleagues show in mice that autophagy can be exploited to boost the efficacy of a dendritic cell vaccine for Mycobacterium tuberculosis.
Chinnaswamy Jagannath et al.
doi:10.1038/nm.1928
Abstract: http://links.ealert.nature.com/ctt?kn=11&m=31848430&r=MTc2NTQyNDEzOQS2&b=2&j=NDYzMzE3ODYS1&mt=1&rt=0
Article: http://links.ealert.nature.com/ctt?kn=70&m=31848430&r=MTc2NTQyNDEzOQS2&b=2&j=NDYzMzE3ODYS1&mt=1&rt=0
Effector T cells control lung inflammation during acute influenza virus infection by producing IL-10 pp277 - 284
Interleukin-10 is known to dampen immune responses and contribute to the persistence of chronic viruses and parasites. Thomas Braciale and his colleagues show in mice that the anti-inflammatory cytokine is produced, along with proinflammatory cytokines, by effector CD4+ and CD8+ T cells during an acute virus infection of the lung, thereby helping to regulate the extent of inflammatory lung damage in response to the virus.
Jie Sun, Rajat Madan, Christopher L Karp and Thomas J Braciale
doi:10.1038/nm.1929
Abstract: http://links.ealert.nature.com/ctt?kn=122&m=31848430&r=MTc2NTQyNDEzOQS2&b=2&j=NDYzMzE3ODYS1&mt=1&rt=0
Article: http://links.ealert.nature.com/ctt?kn=156&m=31848430&r=MTc2NTQyNDEzOQS2&b=2&j=NDYzMzE3ODYS1&mt=1&rt=0
Phase 2 gene therapy trial of an anti-HIV ribozyme in autologous CD34+ cells pp285 - 292
The first phase 2 gene therapy trial for HIV-1 has shown some promising signs. There's a long way to go before this would be a viable approach in people with HIV[mdash]this trial did not show a statistically significant difference in viral load at the primary end point-but other analyses did reveal that the gene therapy seemed to have a modest, but statistically significant, effect at reducing viral load in the treated subjects versus the placebo arm. The study also provides some clues about what to improve in the future.
Ronald T Mitsuyasu et al.
doi:10.1038/nm.1932
Abstract: http://links.ealert.nature.com/ctt?kn=105&m=31848430&r=MTc2NTQyNDEzOQS2&b=2&j=NDYzMzE3ODYS1&mt=1&rt=0
Article: http://links.ealert.nature.com/ctt?kn=108&m=31848430&r=MTc2NTQyNDEzOQS2&b=2&j=NDYzMzE3ODYS1&mt=1&rt=0
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LETTERS
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Effector memory T cell responses are associated with protection of rhesus monkeys from mucosal simian immunodeficiency virus challenge pp293 - 299
Issue:Vaccines that induce T cell responses to simian immunodeficiency virus are able to reduce virus load in infected macaques. Such vaccines typically induce central memory T cells that must expand before gaining full antiviral functions. Picker and his colleagues show that a new replicating anti-SIV vaccine, based on the persistently infecting cytomegalovirus, which preferentially induces effector memory T cells in mucosal tissues, can reduce the likelihood that the macaques become infected in the first place (pages 244-246).
Scott G Hansen et al.
doi:10.1038/nm.1935
Abstract: http://links.ealert.nature.com/ctt?kn=73&m=31848430&r=MTc2NTQyNDEzOQS2&b=2&j=NDYzMzE3ODYS1&mt=1&rt=0
Article: http://links.ealert.nature.com/ctt?kn=155&m=31848430&r=MTc2NTQyNDEzOQS2&b=2&j=NDYzMzE3ODYS1&mt=1&rt=0
Kindlin-3 is required for [beta]2 integrin-mediated leukocyte adhesion to endothelial cells pp300 - 305
Kindlin-3 interacts with [beta]1 and [beta]3 integrins on platelets, and Kindlin-3-deficient mice have defects in platelet activation and blood clotting. Moser et al. now show that these mice also have defects in [beta]2 integrin activation on leukocytes, leading to severely compromised leukocyte adhesion to the endothelium. The combined platelet and leukocyte defects of these mice resemble those seen in individuals with the leukocyte adhesion deficiency syndrome LAD-III. Other papers in this issue by Malinin et al. and Svensson et al. provide evidence that KINDLIN-3 dysfunction does indeed underlie this type of human disease syndrome (pages 249-250, 306-312 and 313-318).
Markus Moser et al.
doi:10.1038/nm.1921
Abstract: http://links.ealert.nature.com/ctt?kn=1&m=31848430&r=MTc2NTQyNDEzOQS2&b=2&j=NDYzMzE3ODYS1&mt=1&rt=0
Article: http://links.ealert.nature.com/ctt?kn=97&m=31848430&r=MTc2NTQyNDEzOQS2&b=2&j=NDYzMzE3ODYS1&mt=1&rt=0
Leukocyte adhesion deficiency-III is caused by mutations in KINDLIN3 affecting integrin activation pp306 - 312
In this issue, three reports show that Kindlin-3 is crucial for activation of multiple classes of integrins in several types of hematopoietic cells. In mice, Kindlin-3 was previously shown to be important for platelet activation and blood clotting, and Moser et al. now show its importance in leukocytes for adhesion to the endothelium. In humans, Svensson et al. and Malinin et al. show that mutation of the gene encoding Kindlin-3 is associated with a disease syndrome involving severe bleeding, infection and osteopetrosis, which Malinin et al. showed could be corrected by bone marrow transplantation (pages 249-250, 300-305 and 313-318).
Lena Svensson et al.
doi:10.1038/nm.1931
Abstract: http://links.ealert.nature.com/ctt?kn=63&m=31848430&r=MTc2NTQyNDEzOQS2&b=2&j=NDYzMzE3ODYS1&mt=1&rt=0
Article: http://links.ealert.nature.com/ctt?kn=117&m=31848430&r=MTc2NTQyNDEzOQS2&b=2&j=NDYzMzE3ODYS1&mt=1&rt=0
A point mutation in KINDLIN3 ablates activation of three integrin subfamilies in humans pp313 - 318
In this issue, three reports show that Kindlin-3 is crucial for activation of multiple classes of integrins in several types of hematopoietic cells. In mice, Kindlin-3 was previously shown to be important for platelet activation and blood clotting, and Moser et al. now show its importance in leukocytes for adhesion to the endothelium. In humans, Svensson et al. and Malinin et al. show that mutation of the gene encoding Kindlin-3 is associated with a disease syndrome involving severe bleeding, infection and osteopetrosis, which Malinin et al. showed could be corrected by bone marrow transplantation (pages 249-250, 300-305 and 306-312).
Nikolay L Malinin et al.
doi:10.1038/nm.1917
Abstract: http://links.ealert.nature.com/ctt?kn=90&m=31848430&r=MTc2NTQyNDEzOQS2&b=2&j=NDYzMzE3ODYS1&mt=1&rt=0
Article: http://links.ealert.nature.com/ctt?kn=26&m=31848430&r=MTc2NTQyNDEzOQS2&b=2&j=NDYzMzE3ODYS1&mt=1&rt=0
Regulation of endocytosis via the oxygen-sensing pathway pp319 - 324
Hypoxia promotes tumor growth by stimulating angiogenesis, glycolysis, resistance to apoptosis and cell invasion. Wang et al. now report that hypoxia also increases the duration of growth factor signaling in tumor cells. They show that hypoxia-inducible factor downregulates the expression of an effector of early endosome fusion, slowing the endocytic recycling of epidermal growth factor receptor and thereby extending its activation and potential to enhance tumor cell proliferation and survival (pages 246-247).
Yi Wang et al.
doi:10.1038/nm.1922
Abstract: http://links.ealert.nature.com/ctt?kn=131&m=31848430&r=MTc2NTQyNDEzOQS2&b=2&j=NDYzMzE3ODYS1&mt=1&rt=0
Article: http://links.ealert.nature.com/ctt?kn=146&m=31848430&r=MTc2NTQyNDEzOQS2&b=2&j=NDYzMzE3ODYS1&mt=1&rt=0
Hypernitrosylated ryanodine receptor calcium release channels are leaky in dystrophic muscle pp325 - 330
Increased calcium levels in dystrophic muscle have damaging consequences. In this report, Bellinger et al. show that nitrosylation of the ryanodine receptor calcium channel, leading to calcium leak through the channel, is an underlying cause of increased calcium levels in the muscle of dystrophic mdx mice. Treatment of the mice with a compound that inhibits calcium leak increases their muscle function and physical activity, pointing to a potential new treatment for muscular dystrophy (pages 243-244).
Andrew M Bellinger et al.
doi:10.1038/nm.1916
Abstract: http://links.ealert.nature.com/ctt?kn=81&m=31848430&r=MTc2NTQyNDEzOQS2&b=2&j=NDYzMzE3ODYS1&mt=1&rt=0
Article: http://links.ealert.nature.com/ctt?kn=150&m=31848430&r=MTc2NTQyNDEzOQS2&b=2&j=NDYzMzE3ODYS1&mt=1&rt=0
Neuroprotective effects of brain-derived neurotrophic factor in rodent and primate models of Alzheimer's disease pp331 - 337
Mark Tuszynski and his colleagues show that brain-derived neurotrophic factor is neuroprotective and can improve cognition in rodent and primate models of Alzheimer's disease.
Alan H Nagahara et al.
doi:10.1038/nm.1912
Abstract: http://links.ealert.nature.com/ctt?kn=113&m=31848430&r=MTc2NTQyNDEzOQS2&b=2&j=NDYzMzE3ODYS1&mt=1&rt=0
Article: http://links.ealert.nature.com/ctt?kn=77&m=31848430&r=MTc2NTQyNDEzOQS2&b=2&j=NDYzMzE3ODYS1&mt=1&rt=0
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TECHNICAL REPORT
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Sensitive in vivo imaging of T cells using a membrane-bound Gaussia princeps luciferase pp338 - 344
Elmer B Santos et al.
doi:10.1038/nm.1930
Abstract: http://links.ealert.nature.com/ctt?kn=34&m=31848430&r=MTc2NTQyNDEzOQS2&b=2&j=NDYzMzE3ODYS1&mt=1&rt=0
Article: http://links.ealert.nature.com/ctt?kn=119&m=31848430&r=MTc2NTQyNDEzOQS2&b=2&j=NDYzMzE3ODYS1&mt=1&rt=0
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