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World Stem Cell Summit 2010

Friday, November 6, 2009

Nature Medicine Contents: November 2009 Volume 15 pp 1229-1333

NATURE MEDICINE

November 2009 Volume 15 Number 11, pp 1229 - 1333

Visit Nature Medicine online to browse the journal.

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Colloquium on Systems Biology and HIV Vaccine Development

We are pleased to invite you to our Colloquium on Systems Biology and HIV Vaccine Development, during which we will explore the potential of systems biology for HIV vaccine design.

February 8-10, 2010
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----------------------
NATURE MEDICINE PODCAST
----------------------
Plunging into patents

As pharmaceutical companies face an impending 'patent cliff', we take a look at the law of the land. Plus, scientists study innate immunity to HIV.

http://links.ealert.nature.com/ctt?kn=16&m=34376181&r=MTc2NTQyNDEzOQS2&b=2&j=NjA1NzMwMTcS1&mt=1&rt=0

----------------------
EDITORIAL
----------------------
Patently naive p1229
doi:10.1038/nm1109-1229
Intellectual-property protection is a key driver of innovation, and researchers are always keen to file patents to shield their discoveries. Yet scientists often have an uninformed view of the value of their intellectual property. This naivete slows down translational research.
http://links.ealert.nature.com/ctt?kn=25&m=34376181&r=MTc2NTQyNDEzOQS2&b=2&j=NjA1NzMwMTcS1&mt=1&rt=0

----------------------
NEWS
----------------------
Wireless medical devices advance, weather balloons aside p1231
Jon Evans
doi:10.1038/nm1109-1231
http://links.ealert.nature.com/ctt?kn=117&m=34376181&r=MTc2NTQyNDEzOQS2&b=2&j=NjA1NzMwMTcS1&mt=1&rt=0

Efforts to improve vaccine stabilization heat up p1232
Meredith Wadman
doi:10.1038/nm1109-1232
http://links.ealert.nature.com/ctt?kn=113&m=34376181&r=MTc2NTQyNDEzOQS2&b=2&j=NjA1NzMwMTcS1&mt=1&rt=0

Researchers come together to study natural HIV resistance p1233
Cassandra Willyard
doi:10.1038/nm1109-1233
http://links.ealert.nature.com/ctt?kn=126&m=34376181&r=MTc2NTQyNDEzOQS2&b=2&j=NjA1NzMwMTcS1&mt=1&rt=0

News in brief pp1234 - 1235
doi:10.1038/nm1109-1234
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Straight talk with...Joan Scott pp1236 - 1237
Genevive Bjorn
doi:10.1038/nm1109-1236
Abstract: http://links.ealert.nature.com/ctt?kn=162&m=34376181&r=MTc2NTQyNDEzOQS2&b=2&j=NjA1NzMwMTcS1&mt=1&rt=0
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Australian committees set to advise on translational medicine p1238
Simon Grose
doi:10.1038/nm1109-1238a
http://links.ealert.nature.com/ctt?kn=146&m=34376181&r=MTc2NTQyNDEzOQS2&b=2&j=NjA1NzMwMTcS1&mt=1&rt=0

In debate over AIDS vaccine success, every detail counts p1238
Roxanne Khamsi
doi:10.1038/nm1109-1238b
http://links.ealert.nature.com/ctt?kn=144&m=34376181&r=MTc2NTQyNDEzOQS2&b=2&j=NjA1NzMwMTcS1&mt=1&rt=0

Patents in Focus
Biomedical patents: Overturning preconceptions p1239
doi:10.1038/nm1109-1239a
http://links.ealert.nature.com/ctt?kn=36&m=34376181&r=MTc2NTQyNDEzOQS2&b=2&j=NjA1NzMwMTcS1&mt=1&rt=0

Patents in Focus
Sluggish generics entry prompts calls for European patent reform p1239
Lucas Laursen
doi:10.1038/nm1109-1239b
http://links.ealert.nature.com/ctt?kn=39&m=34376181&r=MTc2NTQyNDEzOQS2&b=2&j=NjA1NzMwMTcS1&mt=1&rt=0

Patents in Focus
Pharma 'patent trolls' remain mostly the stuff of myth p1240
Stu Hutson
doi:10.1038/nm1109-1240a
http://links.ealert.nature.com/ctt?kn=30&m=34376181&r=MTc2NTQyNDEzOQS2&b=2&j=NjA1NzMwMTcS1&mt=1&rt=0

Patents in Focus
Researchers ponder a patent-free world pp1240 - 1241
Lauren Cahoon
doi:10.1038/nm1109-1240b
http://links.ealert.nature.com/ctt?kn=32&m=34376181&r=MTc2NTQyNDEzOQS2&b=2&j=NjA1NzMwMTcS1&mt=1&rt=0

Patents in Focus
'Machine or transformation test' put to the test itself p1241
Mike May
doi:10.1038/nm1109-1241
http://links.ealert.nature.com/ctt?kn=26&m=34376181&r=MTc2NTQyNDEzOQS2&b=2&j=NjA1NzMwMTcS1&mt=1&rt=0

Patents in Focus
Biosimilars legislation awakens data exclusivity debate p1242
Stu Hutson
doi:10.1038/nm1109-1242a
http://links.ealert.nature.com/ctt?kn=28&m=34376181&r=MTc2NTQyNDEzOQS2&b=2&j=NjA1NzMwMTcS1&mt=1&rt=0

Patents in Focus
Online resource aims to smooth the biomed patent search p1242
Simon Grose
doi:10.1038/nm1109-1242b
http://links.ealert.nature.com/ctt?kn=19&m=34376181&r=MTc2NTQyNDEzOQS2&b=2&j=NjA1NzMwMTcS1&mt=1&rt=0

Patents in Focus
Pharma positions to survive the impending patent cliff p1243
Mike May
doi:10.1038/nm1109-1243a
http://links.ealert.nature.com/ctt?kn=11&m=34376181&r=MTc2NTQyNDEzOQS2&b=2&j=NjA1NzMwMTcS1&mt=1&rt=0

Patents in Focus
Prometheus v. Mayo case in the spotlight p1243
Lauren Cahoon
doi:10.1038/nm1109-1243b
http://links.ealert.nature.com/ctt?kn=8&m=34376181&r=MTc2NTQyNDEzOQS2&b=2&j=NjA1NzMwMTcS1&mt=1&rt=0

----------------------
BOOK REVIEW
----------------------
Rock the cradle p1244
Teresa K Woodruff reviews The Fertility Doctor: John Rock and the Reproductive Revolution by Margaret Marsh and Wanda Ronner
doi:10.1038/nm1109-1244
http://links.ealert.nature.com/ctt?kn=6&m=34376181&r=MTc2NTQyNDEzOQS2&b=2&j=NjA1NzMwMTcS1&mt=1&rt=0

----------------------
NEWS AND VIEWS
----------------------
Sepsis: the dark side of histones pp1245 - 1246
Catherine Chaput and Arturo Zychlinsky
doi:10.1038/nm1109-1245
Injection of activated protein C (APC) is the last resort to rescue a patient with severe sepsis. Research into how APC works reveals that the drug inactivates histones (pages 1318-1321), which are toxic during severe sepsis.
http://links.ealert.nature.com/ctt?kn=3&m=34376181&r=MTc2NTQyNDEzOQS2&b=2&j=NjA1NzMwMTcS1&mt=1&rt=0

Autoimmunity: apoptotic fats grease transcription pp1246 - 1248
Keith B Elkon
doi:10.1038/nm1109-1246
Transcription factors known for handling the body's response to lipids promote clearance of apoptotic cells by macrophages, according to new research (pages 1266-1272). When this process goes awry, autoimmunity can result.
http://links.ealert.nature.com/ctt?kn=68&m=34376181&r=MTc2NTQyNDEzOQS2&b=2&j=NjA1NzMwMTcS1&mt=1&rt=0

Eye vessels saved by rescuing their pericyte partners pp1248 - 1249
David Antonetti
doi:10.1038/nm1109-1248
High blood sugar can lead to diabetic retinopathy and subsequent blindness. Glucose is now found to quench a growth factor that keeps pericytes alive. Without these key support cells, the retinal vasculature degenerates (pages 1298-1306).
http://links.ealert.nature.com/ctt?kn=69&m=34376181&r=MTc2NTQyNDEzOQS2&b=2&j=NjA1NzMwMTcS1&mt=1&rt=0

----------------------
COMMUNITY CORNER
----------------------
Drug may put brakes on Parkinson's disease p1250
doi:10.1038/nm1109-1250
http://links.ealert.nature.com/ctt?kn=74&m=34376181&r=MTc2NTQyNDEzOQS2&b=2&j=NjA1NzMwMTcS1&mt=1&rt=0

----------------------
BETWEEN BEDSIDE AND BENCH
----------------------

Attacking the flu
Flu remains a major killer because of imperfect vaccines and widespread resistance to existing antivirals-problems particularly acute during a pandemic. New findings at the bedside and at the bench could lead to improvements on both fronts. Grace Chen and Kanta Subbarao discuss the implications of research identifying human antibodies than can neutralize a range of viral subtypes. The findings may help lead to a 'universal' vaccine against these diverse and rapidly evolving viruses. Estanislao Nistal-Villan and Adolfo Garcia-Sastre examine two recent studies that reveal the crystal structure of a promising viral drug target, the unique endonuclease domain of the viral polymerase. The findings open the door to the rational design of new influenza virus inhibitors.

Attacking the flu: Neutralizing antibodies may lead to 'universal' vaccine pp1251 - 1252
Grace L Chen and Kanta Subbarao
doi:10.1038/nm1109-1251
http://links.ealert.nature.com/ctt?kn=77&m=34376181&r=MTc2NTQyNDEzOQS2&b=2&j=NjA1NzMwMTcS1&mt=1&rt=0

Attacking the flu: New prospects for the rational design of antivirals pp1253 - 1254
Estanislao Nistal-Villan and Adolfo Garcia-Sastre
doi:10.1038/nm1109-1253
http://links.ealert.nature.com/ctt?kn=42&m=34376181&r=MTc2NTQyNDEzOQS2&b=2&j=NjA1NzMwMTcS1&mt=1&rt=0

----------------------
RESEARCH HIGHLIGHTS
----------------------
Research Highlights pp1256 - 1257
doi:10.1038/nm1109-1256
http://links.ealert.nature.com/ctt?kn=40&m=34376181&r=MTc2NTQyNDEzOQS2&b=2&j=NjA1NzMwMTcS1&mt=1&rt=0


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Autoimmune disease: Treating MS with hypertension drugs
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----------------------
ARTICLES
----------------------
Salmonella disrupts lymph node architecture by TLR4-mediated suppression of homeostatic chemokines pp1259 - 1265
Ashley L St John and Soman N Abraham
doi:10.1038/nm.2036
Soman Abraham and his colleagues report a new mechanism of immune suppression used by Salmonella. The bacteria traffic to lymph nodes, where Salmonella lipopolysaccharide triggers the downmodulation of certain chemokines, disrupting the cellular organization of the lymph node and impairing adaptive immunity.
Abstract: http://links.ealert.nature.com/ctt?kn=163&m=34376181&r=MTc2NTQyNDEzOQS2&b=2&j=NjA1NzMwMTcS1&mt=1&rt=0
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PPAR-d senses and orchestrates clearance of apoptotic cells to promote tolerance pp1266 - 1272
Lata Mukundan et al.
doi:10.1038/nm.2048
Macrophages coordinate the disposal of apoptotic cells. Ajay Chawla and his colleagues show that PPAR-delta, a sensor of fatty acids, is involved in this process. Ingestion of apoptotic cells by macrophages prompts the upregulation of PPAR-delta, which then responds by enhancing the expression of opsonins. Lack of PPAR-delta reduces apoptotic cell clearance and predisposes to autoimmunity (pages 1246-1248).
Abstract: http://links.ealert.nature.com/ctt?kn=152&m=34376181&r=MTc2NTQyNDEzOQS2&b=2&j=NjA1NzMwMTcS1&mt=1&rt=0
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Dual roles for hepatic lectin receptors in the clearance of chilled platelets pp1273 - 1280
Viktoria Rumjantseva et al.
doi:10.1038/nm.2030
Unlike other types of blood components, refrigeration of platelets leads to their rapid clearance from the circulation after transfusion. Platelets must therefore be stored at room temperature, a serious limitation to their use for transfusions. Viktoria Rumjantseva et al. now dissect two platelet clearance pathways by which exposed carbohydrate residues on platelets are recognized by receptors on liver macrophages and hepatocytes, which differentially control the clearance of short-term- and long-term-refrigerated platelets.
Abstract: http://links.ealert.nature.com/ctt?kn=153&m=34376181&r=MTc2NTQyNDEzOQS2&b=2&j=NjA1NzMwMTcS1&mt=1&rt=0
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Nexilin mutations destabilize cardiac Z-disks and lead to dilated cardiomyopathy pp1281 - 1288
David Hassel et al.
doi:10.1038/nm.2037
David Hassel et al. show that mutations affecting the protein nexilin underlie an unusual type of dilated cardiomyopathy characterized by disrupted Z-disk structures in cardiac muscle. Functional studies in zebrafish revealed that nexilin has an essential role in maintaining Z-disk stability and suggested that the disease-causing nexilin mutations found in humans encode proteins that act in a dominant-negative fashion.
Abstract: http://links.ealert.nature.com/ctt?kn=154&m=34376181&r=MTc2NTQyNDEzOQS2&b=2&j=NjA1NzMwMTcS1&mt=1&rt=0
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Notch3 signaling promotes the development of pulmonary arterial hypertension pp1289 - 1297
Xiaodong Li et al.
doi:10.1038/nm.2021
Notch signaling is known to modulate the phenotype of vascular smooth muscle cells. Xiaodong Li et al. now provide evidence for the importance of signaling through the NOTCH3 receptor and its downstream target HES-5 in pulmonary arterial smooth muscle cells for the development of pulmonary arterial hypertension, and they demonstrate the therapeutic potential of targeting this signaling pathway in a mouse model of pulmonary hypertension.
Abstract: http://links.ealert.nature.com/ctt?kn=155&m=34376181&r=MTc2NTQyNDEzOQS2&b=2&j=NjA1NzMwMTcS1&mt=1&rt=0
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Activation of PKC-delta and SHP-1 by hyperglycemia causes vascular cell apoptosis and diabetic retinopathy pp1298 - 1306
Pedro Geraldes et al.
doi:10.1038/nm.2052
Vascular defects resulting from pericyte cell death are thought to be a major underlying cause of diabetic retinopathy. Pedro Geraldes et al. investigate the signaling mechanisms by which hyperglycemia leads to pericyte death and delineate a pathway by which PKC-delta activation decreases antiapoptotic PDGF receptor signaling
(pages 1248-1249).
Abstract: http://links.ealert.nature.com/ctt?kn=156&m=34376181&r=MTc2NTQyNDEzOQS2&b=2&j=NjA1NzMwMTcS1&mt=1&rt=0
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----------------------
LETTERS
----------------------
Foxo1 integrates insulin signaling with mitochondrial function in the liver pp1307 - 1311
Zhiyong Cheng et al.
doi:10.1038/nm.2049
Hepatic insulin resistance is often associated with mitochondrial dysfunction, leading to defects in cellular activity. Morris White and his colleagues have now found that continued activity of the transcription factor Foxo1, which is normally inhibited by insulin signaling, is at the crux of this dysfunction, and, when it is genetically deleted, proper mitochondrial function in two models of insulin resistance is restored.
Abstract: http://links.ealert.nature.com/ctt?kn=157&m=34376181&r=MTc2NTQyNDEzOQS2&b=2&j=NjA1NzMwMTcS1&mt=1&rt=0
Article: http://links.ealert.nature.com/ctt?kn=99&m=34376181&r=MTc2NTQyNDEzOQS2&b=2&j=NjA1NzMwMTcS1&mt=1&rt=0

Inhibition of the histone demethylase LSD1 blocks alpha-herpesvirus lytic replication and reactivation from latency pp1312 - 1317
Yu Liang et al.
doi:10.1038/nm.2051
Viral gene expression can be regulated by chromatin methylation and demethylation. Thomas Kristie and his colleagues have identified a histone demethylase that is required to remove repressive methylation from the immediate early promoters of two alpha-herpesviruses. Monoamine oxidase inhibitors, which block this demethylase, prevented lytic replication and reactivation from latency.
Abstract: http://links.ealert.nature.com/ctt?kn=158&m=34376181&r=MTc2NTQyNDEzOQS2&b=2&j=NjA1NzMwMTcS1&mt=1&rt=0
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Extracellular histones are major mediators of death in sepsis pp1318 - 1321
Jun Xu et al.
doi:10.1038/nm.2053
Extracellular histones released in response to inflammatory challenge contribute to organ failure and death during sepsis. Histone-specific antibodies and activated protein C had beneficial effects in animal models of sepsis, pointing to extracellular histones as therapeutics targets for sepsis and other inflammatory conditions (pages 1245-1246).
Abstract: http://links.ealert.nature.com/ctt?kn=148&m=34376181&r=MTc2NTQyNDEzOQS2&b=2&j=NjA1NzMwMTcS1&mt=1&rt=0
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----------------------
TECHNICAL REPORTS
----------------------
Major histocompatibility complex genotyping with massively parallel pyrosequencing pp1322 - 1326
Roger W Wiseman et al.
doi:10.1038/nm.2038
Abstract: http://links.ealert.nature.com/ctt?kn=149&m=34376181&r=MTc2NTQyNDEzOQS2&b=2&j=NjA1NzMwMTcS1&mt=1&rt=0
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Matrix-insensitive protein assays push the limits of biosensors in medicine pp1327 - 1332
Richard S Gaster et al.
doi:10.1038/nm.2032
Abstract: http://links.ealert.nature.com/ctt?kn=150&m=34376181&r=MTc2NTQyNDEzOQS2&b=2&j=NjA1NzMwMTcS1&mt=1&rt=0
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----------------------
ERRATUM
----------------------
Erratum: A selective inhibitor of the immunoproteasome subunit LMP7 blocks cytokine production and attenuates progression of experimental arthritis p1333
Tony Muchamuel et al.
doi:10.1038/nm1109-1333a
http://links.ealert.nature.com/ctt?kn=170&m=34376181&r=MTc2NTQyNDEzOQS2&b=2&j=NjA1NzMwMTcS1&mt=1&rt=0

----------------------
CORRIGENDUM
----------------------
Corrigendum: Baseline Ad5 serostatus does not predict Ad5 HIV vaccine-induced expansion of adenovirus-specific CD4+ T cells p1333
Natalie A Hutnick et al.
doi:10.1038/nm1109-1333b
http://links.ealert.nature.com/ctt?kn=165&m=34376181&r=MTc2NTQyNDEzOQS2&b=2&j=NjA1NzMwMTcS1&mt=1&rt=0

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