June 2009 Volume 15 Number 6, pp 585 - 706
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Novel strategies for HIV therapy
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Two research teams are proposing the use of known compounds-the mild surfactant glycerol monolaurate and a protein called griffithsin that could be scaled up in tobacco-be used to block distinct steps in the early stages of HIV infection. Both teams already have commercial links but what challenges lay ahead?
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NATURE MEDICINE PODCAST
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Disease fighting dairy
Tune in for up-to-date biomedical news, including a look at whether probiotic yogurt could become part of HIV therapy.
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EDITORIAL
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Be prepared p585
Pushing 'shovel-ready' technologies through the pipeline has the potential to substantially bolster defenses against the emerging flu strain and future pandemics.
doi:10.1038/nm0609-585
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NEWS
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Computational tools evolve to reveal patterns in flu data p587
Kirsten Dorans
doi:10.1038/nm0609-587
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Bone seems susceptible to range of drugs p588
Charlotte Schubert
doi:10.1038/nm0609-588
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UK budget puts faith in biomedical sector p589
Jon Evans
doi:10.1038/nm0609-589a
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NIH draft seen as 'working compromise' p589
Stu Hutson
doi:10.1038/nm0609-589b
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Mind the skills gap p589
Jon Evans
doi:10.1038/nm0609-589c
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News in brief pp590 - 591
doi:10.1038/nm0609-590
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Straight talk with ... Otto Yang and Patrick Miller pp592 - 593
Kirsten Dorans
doi:10.1038/nm0609-592
Abstract: http://links.ealert.nature.com/ctt?kn=65&m=33359838&r=MTc2NTQyNDEzOQS2&b=2&j=NTA4OTc4NDYS1&mt=1&rt=0
Article: http://links.ealert.nature.com/ctt?kn=45&m=33359838&r=MTc2NTQyNDEzOQS2&b=2&j=NTA4OTc4NDYS1&mt=1&rt=0
A cultured response to HIV pp594 - 597
In recent years, research has continued to demonstrate that HIV wreaks terrible havoc in the gut. A few scientists believe that probiotic yogurt might help to counter some of the virus's devastating effects on the intestine. Melinda Wenner reports on a pilot project that is helping a Tanzanian community make its own probiotic yogurt for HIV-infected locals and empowering women in the process.
Melinda Wenner
doi:10.1038/nm0609-594
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Publication of fake journals raises ethical questions p598
Stu Hutson
doi:10.1038/nm0609-598a
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Malaria drug delivery program launches amid skepticism p598
Nayanah Siva
doi:10.1038/nm0609-598b
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BOOK REVIEW
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Worried about your memory? p599
Howard Eichenbaum reviews Can't Remember What I Forgot: The Good News from the Front Lines of Memory Research by Sue Halpern
doi:10.1038/nm0609-599
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CORRESPONDENCE
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Mesenchymal stem cells: another anti-inflammatory treatment for sepsis? pp601 - 602
Guillaume Monneret
doi:10.1038/nm0609-601
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Reply to 'Mesenchymal stem cells: another anti-inflammatory treatment for sepsis?' p602
Krisztian Nemeth et al.
doi:10.1038/nm0609-602a
http://links.ealert.nature.com/ctt?kn=23&m=33359838&r=MTc2NTQyNDEzOQS2&b=2&j=NTA4OTc4NDYS1&mt=1&rt=0
Reassessing the human mammary stem cell concept by modeling limiting dilution transplantation assays pp602 - 604
Thierry Bonnefoix and Mary Callanan
doi:10.1038/nm0609-602b
http://links.ealert.nature.com/ctt?kn=7&m=33359838&r=MTc2NTQyNDEzOQS2&b=2&j=NTA4OTc4NDYS1&mt=1&rt=0
Reply to 'Reassessing the human mammary stem cell concept by modeling limiting dilution transplantation assays' pp604 - 605
Peter Eirew, Miao Yu, Ryan Brinkman and Connie J Eaves
doi:10.1038/nm0609-604
http://links.ealert.nature.com/ctt?kn=169&m=33359838&r=MTc2NTQyNDEzOQS2&b=2&j=NTA4OTc4NDYS1&mt=1&rt=0
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NEWS AND VIEWS
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In the shadow of the thrombus pp607 - 608
Platelets accumulate on the downstream face of a developing blood clot after local changes in blood flow. These findings offer new insights into how platelets pile up at sites of vascular injury (pages 665-673).
Lawrence Brass
doi:10.1038/nm0609-607
http://links.ealert.nature.com/ctt?kn=25&m=33359838&r=MTc2NTQyNDEzOQS2&b=2&j=NTA4OTc4NDYS1&mt=1&rt=0
Tension in the vasculature pp608 - 610
Blood vessels arise from progenitor cells, grow and branch by sprouting from preexisting vessels and remodel by splitting longitudinally. A new study proposes an additional mechanism. It seems that vascularization can proceed through the mechanical translocation and expansion of existing vessels, which loop into vascularising tissue (pages 657-664).
Andrew V Benest and Hellmut G Augustin
doi:10.1038/nm0609-608
http://links.ealert.nature.com/ctt?kn=136&m=33359838&r=MTc2NTQyNDEzOQS2&b=2&j=NTA4OTc4NDYS1&mt=1&rt=0
Stomaching calcium for bone health pp610 - 612
Calcium deficiency in the elderly is associated with low gastric acid secretion and bone loss. A new study linking defects in gastric acid secretion with bone destruction and impaired mineralization bolsters the view that calcium supplements can prevent these bone defects-but do they all work (pages 674-681)?
Brendan F Boyce
doi:10.1038/nm0609-610
http://links.ealert.nature.com/ctt?kn=39&m=33359838&r=MTc2NTQyNDEzOQS2&b=2&j=NTA4OTc4NDYS1&mt=1&rt=0
IFN-a wakes up sleeping hematopoietic stem cells pp612 - 613
The cytokine interferon-a stimulates the turnover and proliferation of hematopoietic cells in vivo (pages 696-700). The findings hint at a new strategy to treat hematopoietic cancers.
Emmanuelle Passegue and Patricia Ernst
doi:10.1038/nm0609-612
http://links.ealert.nature.com/ctt?kn=63&m=33359838&r=MTc2NTQyNDEzOQS2&b=2&j=NTA4OTc4NDYS1&mt=1&rt=0
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COMMUNITY CORNER
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Compound clamps down on prostate cancer p615
doi:10.1038/nm0609-615
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BETWEEN BEDSIDE AND BENCH
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Expansion and contraction
Bariatric surgery is not only one of the most immediate and effective ways to slim down: recent clinical data show that certain procedures are also particularly good at quelling type 2 diabetes. In "Bedside to Bench," Allison Goldfine, Steven Shoelson and Vincent Aguirre outline how researchers can better understand these new clinical findings at the mechanistic level. In the accompanying "Bench to Bedside," Jorge Plutzky takes a look how proper regulation of the storage of fatty acids helps maintain their effectiveness as signaling molecules and reins in their potential pathological effects. Such research is leading to new ways of thinking about how to combat type 2 diabetes.
Expansion and contraction: treating diabetes with bariatric surgery pp616 - 617
Allison B Goldfine, Steven E Shoelson and Vincent Aguirre
doi:10.1038/nm0609-616
http://links.ealert.nature.com/ctt?kn=150&m=33359838&r=MTc2NTQyNDEzOQS2&b=2&j=NTA4OTc4NDYS1&mt=1&rt=0
Expansion and contraction: the mighty, mighty fatty acid pp618 - 619
Jorge Plutzky
doi:10.1038/nm0609-618
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RESEARCH HIGHLIGHTS
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Research Highlights pp620 - 621
doi:10.1038/nm0609-620
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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.
Early Bird Deadline: September 8, 2009
Abstract Submission: Deadline: August 21, 2009
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BRIEF COMMUNICATION
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Netting neutrophils in autoimmune small-vessel vasculitis pp623 - 625
Neutrophils release neutrophil extracellular traps (NETs), chromatin fibers that can ensnare bacteria. In small-vessel vasculitis (SVV), a chronic inflammatory condition linked to antineutrophil autoantibodies, these NETs express SVV-associated autoantigens, accumulate in inflamed kidneys and promote the autoimmune response against neutrophils in people with SVV.
Kai Kessenbrock et al.
doi:10.1038/nm.1959
Abstract: http://links.ealert.nature.com/ctt?kn=13&m=33359838&r=MTc2NTQyNDEzOQS2&b=2&j=NTA4OTc4NDYS1&mt=1&rt=0
Article: http://links.ealert.nature.com/ctt?kn=20&m=33359838&r=MTc2NTQyNDEzOQS2&b=2&j=NTA4OTc4NDYS1&mt=1&rt=0
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ARTICLES
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Myelin-specific T cells also recognize neuronal autoantigen in a transgenic mouse model of multiple sclerosis pp626 - 632
T-cell recognition of autoantigens is important in the development of autoimmune disease. Now, Hartmut Wekerle and his colleagues demonstrate that organ-specific autoimmune responses may be driven by T cells that simultaneously respond to two different autoantigens found within the same target tissue.
Gurumoorthy Krishnamoorthy et al.
doi:10.1038/nm.1975
Abstract: http://links.ealert.nature.com/ctt?kn=139&m=33359838&r=MTc2NTQyNDEzOQS2&b=2&j=NTA4OTc4NDYS1&mt=1&rt=0
Article: http://links.ealert.nature.com/ctt?kn=17&m=33359838&r=MTc2NTQyNDEzOQS2&b=2&j=NTA4OTc4NDYS1&mt=1&rt=0
Prostaglandin E2-EP4 signaling promotes immune inflammation through TH1 cell differentiation and TH17 cell expansion pp633 - 640
Prostaglandins play a key role in inflammation in a variety of settings. Now, Shuh Narumiya and colleagues show that prostaglandin E2 drives the production of inflammatory T helper cells, and that this can be blocked by inhibiting its EP4 receptor subtype. EP4 inhibitors were also effective at inhibiting disease pathogenesis in animal models of two inflammatory diseases.
Chengcan Yao et al.
doi:10.1038/nm.1968
Abstract: http://links.ealert.nature.com/ctt?kn=43&m=33359838&r=MTc2NTQyNDEzOQS2&b=2&j=NTA4OTc4NDYS1&mt=1&rt=0
Article: http://links.ealert.nature.com/ctt?kn=134&m=33359838&r=MTc2NTQyNDEzOQS2&b=2&j=NTA4OTc4NDYS1&mt=1&rt=0
Toll-like receptor 2 ligands on the staphylococcal cell wall downregulate superantigen-induced T cell activation and prevent toxic shock syndrome pp641 - 648
Staphylococcal superantigens are potent activators of T cells, causing toxic shock syndrome and death. But surprisingly few staphylococcal infections of humans are associated with TSS, even though the bacteria produce the superantigen toxins. Joaquin Madrenas and his colleagues report that other components of the bacteria can downregulate the superantigen-induced T cell activation, protecting the host from death by TSS.
Thu A Chau et al.
doi:10.1038/nm.1965
Abstract: http://links.ealert.nature.com/ctt?kn=28&m=33359838&r=MTc2NTQyNDEzOQS2&b=2&j=NTA4OTc4NDYS1&mt=1&rt=0
Article: http://links.ealert.nature.com/ctt?kn=60&m=33359838&r=MTc2NTQyNDEzOQS2&b=2&j=NTA4OTc4NDYS1&mt=1&rt=0
Cyclophilin A enhances vascular oxidative stress and the development of angiotensin II-induced aortic aneurysms pp649 - 656
The pathogenesis of aortic aneurysms involves inflammatory cell recruitment and increased levels of reactive oxygen species and matrix metalloproteases. Kimio Satoh et al. now mechanistically link the protein cyclophilin A-expressed in vascular smooth muscle cells-to these known mediators of aortic aneurysm formation and provide evidence in both mice and humans for the importance of cyclophilin A in aortic aneurysm formation.
Kimio Satoh et al.
doi:10.1038/nm.1958
Abstract: http://links.ealert.nature.com/ctt?kn=170&m=33359838&r=MTc2NTQyNDEzOQS2&b=2&j=NTA4OTc4NDYS1&mt=1&rt=0
Article: http://links.ealert.nature.com/ctt?kn=153&m=33359838&r=MTc2NTQyNDEzOQS2&b=2&j=NTA4OTc4NDYS1&mt=1&rt=0
Biomechanical regulation of blood vessel growth during tissue vascularization pp657 - 664
In this report, Witold Kilarski et al. show that the rapid formation of new vessels in healing wound tissue does not depend on endothelial cell proliferation and sprouting, which typically have been presumed to be needed for the growth of new blood vessels. Instead, preexisting vessels enlarge and translocate, a process driven by the tension generated by contracting fibroblasts and/or myofibroblasts (pages 608-610).
Witold W Kilarski et al.
doi:10.1038/nm.1985
Abstract: http://links.ealert.nature.com/ctt?kn=71&m=33359838&r=MTc2NTQyNDEzOQS2&b=2&j=NTA4OTc4NDYS1&mt=1&rt=0
Article: http://links.ealert.nature.com/ctt?kn=5&m=33359838&r=MTc2NTQyNDEzOQS2&b=2&j=NTA4OTc4NDYS1&mt=1&rt=0
A shear gradient-dependent platelet aggregation mechanism drives thrombus formation pp665 - 673
Warwick Nesbitt, Erik Westein and coworkers describe a new mechanistic model for thrombus growth within a blood vessel, providing evidence that blood flow shear gradients-which can arise from vessel injury, stenosis or obstruction-are important in driving thrombus formation. Rapid changes in blood shear rates lead to dynamic restructuring of membranous structures, called 'tethers', on the platelet surface, facilitating stable platelet deposition onto a growing thrombus (pages 607-608).
Warwick S Nesbitt et al.
doi:10.1038/nm.1955
Abstract: http://links.ealert.nature.com/ctt?kn=66&m=33359838&r=MTc2NTQyNDEzOQS2&b=2&j=NTA4OTc4NDYS1&mt=1&rt=0
Article: http://links.ealert.nature.com/ctt?kn=137&m=33359838&r=MTc2NTQyNDEzOQS2&b=2&j=NTA4OTc4NDYS1&mt=1&rt=0
Impaired gastric acidification negatively affects calcium homeostasis and bone mass pp674 - 681
Proper calcium levels are needed to maintain healthy bones. Michael Amling and his colleagues now show that gastric acidification is a key part of in this process. These findings have possible important clinical implications for patients with osteoporosis and/or those on proton-pump inhibitors, as well as those with a rare genetic disease that causes excess bone mass.
Thorsten Schinke et al.
doi:10.1038/nm.1963
Abstract: http://links.ealert.nature.com/ctt?kn=34&m=33359838&r=MTc2NTQyNDEzOQS2&b=2&j=NTA4OTc4NDYS1&mt=1&rt=0
Article: http://links.ealert.nature.com/ctt?kn=19&m=33359838&r=MTc2NTQyNDEzOQS2&b=2&j=NTA4OTc4NDYS1&mt=1&rt=0
Inhibition of osteoblastic bone formation by nuclear factor-kB pp682 - 689
It has been well shown that NF-kB has a crucial role in promoting the maturation of bone-resorbing osteoclasts. Now, Cun-Yu Wang and his colleagues show that it also has a role in inhibiting the function of mature bone-forming osteoblasts. They go on to show that deficiency of NF-kB specifically in osteoblasts increases bone formation and protects against bone loss in experimentally-induced osteoporosis in mice.
Jia Chang et al.
doi:10.1038/nm.1954
Abstract: http://links.ealert.nature.com/ctt?kn=48&m=33359838&r=MTc2NTQyNDEzOQS2&b=2&j=NTA4OTc4NDYS1&mt=1&rt=0
Article: http://links.ealert.nature.com/ctt?kn=76&m=33359838&r=MTc2NTQyNDEzOQS2&b=2&j=NTA4OTc4NDYS1&mt=1&rt=0
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LETTERS
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Prophylactic treatment with sialic acid metabolites precludes the development of the myopathic phenotype in the DMRV-hIBM mouse model pp690 - 695
In a new report, Satoru Noguchi and his colleagues have shown that oral administration of various sialic acid compounds helps improve the behavior of skeletal muscles in a mouse model of a severely debilitating human muscle disease-one with no current treatment option. Given the simplicity of their approach, it is possible these findings could have immediate clinical impact.
May Christine V Malicdan et al.
doi:10.1038/nm.1956
Abstract: http://links.ealert.nature.com/ctt?kn=87&m=33359838&r=MTc2NTQyNDEzOQS2&b=2&j=NTA4OTc4NDYS1&mt=1&rt=0
Article: http://links.ealert.nature.com/ctt?kn=166&m=33359838&r=MTc2NTQyNDEzOQS2&b=2&j=NTA4OTc4NDYS1&mt=1&rt=0
Interferon regulatory factor-2 protects quiescent hematopoietic stem cells from type I interferon-dependent exhaustion pp696 - 700
Although type I interferons such as interferon-a are well known to protect against viral infection, they may have other physiological effects in the uninfected state. Taku Sato et al. now show that type I interferon signaling in hematopoietic stem cells promotes their proliferation and impairs their ability to reconstitute the hematopoietic system (pages 696-700).
Taku Sato et al.
doi:10.1038/nm.1973
Abstract: http://links.ealert.nature.com/ctt?kn=124&m=33359838&r=MTc2NTQyNDEzOQS2&b=2&j=NTA4OTc4NDYS1&mt=1&rt=0
Article: http://links.ealert.nature.com/ctt?kn=112&m=33359838&r=MTc2NTQyNDEzOQS2&b=2&j=NTA4OTc4NDYS1&mt=1&rt=0
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TECHNICAL REPORT
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Sustained in vitro intestinal epithelial culture within a Wnt-dependent stem cell niche pp701 - 706
Akifumi Ootani et al.
doi:10.1038/nm.1951
Abstract: http://links.ealert.nature.com/ctt?kn=14&m=33359838&r=MTc2NTQyNDEzOQS2&b=2&j=NTA4OTc4NDYS1&mt=1&rt=0
Article: http://links.ealert.nature.com/ctt?kn=108&m=33359838&r=MTc2NTQyNDEzOQS2&b=2&j=NTA4OTc4NDYS1&mt=1&rt=0
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