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 naiveté slows down translational research.

Abstract - | Full Text - Patently naive | PDF (88 KB) - Patently naive

Wireless medical devices advance, weather balloons aside - p1231

Jon Evans

doi:10.1038/nm1109-1231

Full Text - Wireless medical devices advance, weather balloons aside | PDF (183 KB) - Wireless medical devices advance, weather balloons aside

Efforts to improve vaccine stabilization heat up - p1232

Meredith Wadman

doi:10.1038/nm1109-1232

Full Text - Efforts to improve vaccine stabilization heat up | PDF (197 KB) - Efforts to improve vaccine stabilization heat up

Researchers come together to study natural HIV resistance - p1233

Cassandra Willyard

doi:10.1038/nm1109-1233

Full Text - Researchers come together to study natural HIV resistance | PDF (266 KB) - Researchers come together to study natural HIV resistance

News in brief - pp1234 - 1235

doi:10.1038/nm1109-1234

Full Text - News in brief | PDF (881 KB) - News in brief

Straight talk with...Joan Scott - pp1236 - 1237

Genevive Bjorn

doi:10.1038/nm1109-1236

The Genetics & Public Policy Center (GPPC), located within the Johns Hopkins Berman Institute of Bioethics in Washington, DC, monitors advances in human genetics, including genetic testing, and their translation into clinical medicine. In September 2009, Joan Scott was named the new director of the center. Scott spoke with Genevive Bjorn about the twists and turns of using information from the double helix.

Abstract - | Full Text - Straight talk with...Joan Scott | PDF (489 KB) - Straight talk with...Joan Scott

Australian committees set to advise on translational medicine - p1238

Simon Grose

doi:10.1038/nm1109-1238a

Full Text - Australian committees set to advise on translational medicine | PDF (78 KB) - Australian committees set to advise on translational medicine

In debate over AIDS vaccine success, every detail counts - p1238

Roxanne Khamsi

doi:10.1038/nm1109-1238b

Full Text - In debate over AIDS vaccine success, every detail counts | PDF (78 KB) - In debate over AIDS vaccine success, every detail counts

Patents in Focus

Biomedical patents: Overturning preconceptions - p1239

doi:10.1038/nm1109-1239a

Full Text - Biomedical patents: Overturning preconceptions | PDF (201 KB) - Biomedical patents: Overturning preconceptions

Patents in Focus

Sluggish generics entry prompts calls for European patent reform - p1239

Lucas Laursen

doi:10.1038/nm1109-1239b

Full Text - Sluggish generics entry prompts calls for European patent reform | PDF (201 KB) - Sluggish generics entry prompts calls for European patent reform

Patents in Focus

Pharma 'patent trolls' remain mostly the stuff of myth - p1240

Stu Hutson

doi:10.1038/nm1109-1240a

Full Text - Pharma 'patent trolls' remain mostly the stuff of myth | PDF (86 KB) - Pharma 'patent trolls' remain mostly the stuff of myth

Patents in Focus

Researchers ponder a patent-free world - pp1240 - 1241

Lauren Cahoon

doi:10.1038/nm1109-1240b

Full Text - Researchers ponder a patent-free world | PDF (254 KB) - Researchers ponder a patent-free world

Patents in Focus

'Machine or transformation test' put to the test itself - p1241

Mike May

doi:10.1038/nm1109-1241

Full Text - 'Machine or transformation test' put to the test itself | PDF (171 KB) - 'Machine or transformation test' put to the test itself

Patents in Focus

Biosimilars legislation awakens data exclusivity debate - p1242

Stu Hutson

doi:10.1038/nm1109-1242a

Full Text - Biosimilars legislation awakens data exclusivity debate | PDF (88 KB) - Biosimilars legislation awakens data exclusivity debate

Patents in Focus

Online resource aims to smooth the biomed patent search - p1242

Simon Grose

doi:10.1038/nm1109-1242b

Full Text - Online resource aims to smooth the biomed patent search | PDF (88 KB) - Online resource aims to smooth the biomed patent search

Patents in Focus

Pharma positions to survive the impending patent cliff - p1243

Mike May

doi:10.1038/nm1109-1243a

Full Text - Pharma positions to survive the impending patent cliff | PDF (142 KB) - Pharma positions to survive the impending patent cliff

Patents in Focus

Prometheus v. Mayo case in the spotlight - p1243

Lauren Cahoon

doi:10.1038/nm1109-1243b

Full Text - Prometheus v. Mayo case in the spotlight | PDF (142 KB) - Prometheus v. Mayo case in the spotlight

Rock the cradle - p1244

Teresa K Woodruff reviews The Fertility Doctor: John Rock and the Reproductive Revolution by Margaret Marsh & Wanda Ronner

doi:10.1038/nm1109-1244

Full Text - Rock the cradle | PDF (88 KB) - Rock the cradle

Sepsis: the dark side of histones - pp1245 - 1246

Catherine Chaput & 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.

Full Text - Sepsis: the dark side of histones | PDF (338 KB) - Sepsis: the dark side of histones

See also: Letter by Xu et al.

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.

Full Text - Autoimmunity: apoptotic fats grease transcription | PDF (1,281 KB) - Autoimmunity: apoptotic fats grease transcription

See also: Article by Mukundan et al.

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).

Full Text - Eye vessels saved by rescuing their pericyte partners | PDF (762 KB) - Eye vessels saved by rescuing their pericyte partners

See also: Article by Geraldes et al.

Drug may put brakes on Parkinson's disease - p1250

doi:10.1038/nm1109-1250

Full Text - Drug may put brakes on Parkinson's disease | PDF (114 KB) - Drug may put brakes on Parkinson's disease

Attacking the flu: Neutralizing antibodies may lead to 'universal' vaccine - pp1251 - 1252

Grace L Chen & Kanta Subbarao

doi:10.1038/nm1109-1251

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-Villán and Adolfo García-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.

Abstract - | Full Text - Attacking the flu: Neutralizing antibodies may lead to 'universal' vaccine | PDF (399 KB) - Attacking the flu: Neutralizing antibodies may lead to 'universal' vaccine

Attacking the flu: New prospects for the rational design of antivirals - pp1253 - 1254

Estanislao Nistal-Villán & Adolfo García-Sastre

doi:10.1038/nm1109-1253

Full Text - Attacking the flu: New prospects for the rational design of antivirals | PDF (167 KB) - Attacking the flu: New prospects for the rational design of antivirals

Research Highlights - pp1256 - 1257

doi:10.1038/nm1109-1256

Full Text - Research Highlights | PDF (173 KB) - Research Highlights

Salmonella disrupts lymph node architecture by TLR4-mediated suppression of homeostatic chemokines - pp1259 - 1265

Ashley L St John & 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 - | Full Text - Salmonella disrupts lymph node architecture by TLR4-mediated suppression of homeostatic chemokines | PDF (1,138 KB) - Salmonella disrupts lymph node architecture by TLR4-mediated suppression of homeostatic chemokines | Supplementary information

PPAR- senses and orchestrates clearance of apoptotic cells to promote tolerance - pp1266 - 1272

Lata Mukundan, Justin I Odegaard, Christine R Morel, Jose E Heredia, Julia W Mwangi, Roberto R Ricardo-Gonzalez, Y P Sharon Goh, Alex Red Eagle, Shannon E Dunn, Jennifer U H Awakuni, Khoa D Nguyen, Lawrence Steinman, Sara A Michie & Ajay Chawla

doi:10.1038/nm.2048

Macrophages coordinate the disposal of apoptotic cells. Ajay Chawla and his colleagues show that PPAR-, a sensor of fatty acids, is involved in this process. Ingestion of apoptotic cells by macrophages prompts the upregulation of PPAR-, which then responds by enhancing the expression of opsonins. Lack of PPAR- reduces apoptotic cell clearance and predisposes to autoimmunity (pages 1246–1248).

Abstract - | Full Text - PPAR- senses and orchestrates clearance of apoptotic cells to promote tolerance | PDF (603 KB) - PPAR- senses and orchestrates clearance of apoptotic cells to promote tolerance | Supplementary information

See also: News and Views by Elkon

Dual roles for hepatic lectin receptors in the clearance of chilled platelets - pp1273 - 1280

Viktoria Rumjantseva, Prabhjit K Grewal, Hans H Wandall, Emma C Josefsson, Anne Louise Sørensen, Göran Larson, Jamey D Marth, John H Hartwig & Karin M Hoffmeister

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 - | Full Text - Dual roles for hepatic lectin receptors in the clearance of chilled platelets | PDF (930 KB) - Dual roles for hepatic lectin receptors in the clearance of chilled platelets | Supplementary information

Nexilin mutations destabilize cardiac Z-disks and lead to dilated cardiomyopathy - pp1281 - 1288

David Hassel, Tillman Dahme, Jeanette Erdmann, Benjamin Meder, Andreas Huge, Monika Stoll, Steffen Just, Alexander Hess, Philipp Ehlermann, Dieter Weichenhan, Matthias Grimmler, Henrike Liptau, Roland Hetzer, Vera Regitz-Zagrosek, Christine Fischer, Peter Nürnberg, Heribert Schunkert, Hugo A Katus & Wolfgang Rottbauer

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 - | Full Text - Nexilin mutations destabilize cardiac Z-disks and lead to dilated cardiomyopathy | PDF (2,707 KB) - Nexilin mutations destabilize cardiac Z-disks and lead to dilated cardiomyopathy | Supplementary information

Notch3 signaling promotes the development of pulmonary arterial hypertension - pp1289 - 1297

Xiaodong Li, Xiaoxue Zhang, Robin Leathers, Ayako Makino, Chengqun Huang, Pouria Parsa, Jesus Macias, Jason X-J Yuan, Stuart W Jamieson & Patricia A Thistlethwaite

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 - | Full Text - Notch3 signaling promotes the development of pulmonary arterial hypertension | PDF (1,378 KB) - Notch3 signaling promotes the development of pulmonary arterial hypertension | Supplementary information

Activation of PKC- and SHP-1 by hyperglycemia causes vascular cell apoptosis and diabetic retinopathy - pp1298 - 1306

Pedro Geraldes, Junko Hiraoka-Yamamoto, Motonobu Matsumoto, Allen Clermont, Michael Leitges, Andre Marette, Lloyd P Aiello, Timothy S Kern & George L King

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- activation decreases antiapoptotic PDGF receptor signaling (pages 1248–1249).

Abstract - | Full Text - Activation of PKC- and SHP-1 by hyperglycemia causes vascular cell apoptosis and diabetic retinopathy | PDF (1,387 KB) - Activation of PKC- and SHP-1 by hyperglycemia causes vascular cell apoptosis and diabetic retinopathy | Supplementary information

See also: News and Views by Antonetti

Foxo1 integrates insulin signaling with mitochondrial function in the liver - pp1307 - 1311

Zhiyong Cheng, Shaodong Guo, Kyle Copps, Xiaochen Dong, Ramya Kollipara, Joseph T Rodgers, Ronald A Depinho, Pere Puigserver & Morris F White

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 - | Full Text - Foxo1 integrates insulin signaling with mitochondrial function in the liver | PDF (1,476 KB) - Foxo1 integrates insulin signaling with mitochondrial function in the liver | Supplementary information

Inhibition of the histone demethylase LSD1 blocks -herpesvirus lytic replication and reactivation from latency - pp1312 - 1317

Yu Liang, Jodi L Vogel, Aarthi Narayanan, Hua Peng & Thomas M Kristie

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 -herpesviruses. Monoamine oxidase inhibitors, which block this demethylase, prevented lytic replication and reactivation from latency.

Abstract - | Full Text - Inhibition of the histone demethylase LSD1 blocks -herpesvirus lytic replication and reactivation from latency | PDF (587 KB) - Inhibition of the histone demethylase LSD1 blocks -herpesvirus lytic replication and reactivation from latency | Supplementary information

Extracellular histones are major mediators of death in sepsis - pp1318 - 1321

Jun Xu, Xiaomei Zhang, Rosana Pelayo, Marc Monestier, Concetta T Ammollo, Fabrizio Semeraro, Fletcher B Taylor, Naomi L Esmon, Florea Lupu & Charles T Esmon

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 - | Full Text - Extracellular histones are major mediators of death in sepsis | PDF (1,251 KB) - Extracellular histones are major mediators of death in sepsis | Supplementary information

See also: News and Views by Chaput & Zychlinsky

Major histocompatibility complex genotyping with massively parallel pyrosequencing - pp1322 - 1326

Roger W Wiseman, Julie A Karl, Benjamin N Bimber, Claire E O'Leary, Simon M Lank, Jennifer J Tuscher, Ann M Detmer, Pascal Bouffard, Natalya Levenkova, Cynthia L Turcotte, Edward Szekeres Jr, Chris Wright, Timothy Harkins & David H O'Connor

doi:10.1038/nm.2038

Nonhuman primates are key preclinical models for infectious disease, vaccine development and transplantation research, but their use has been hampered by the complexity and diversity of their major histocompatibility complex (MHC) class I genotypes. Wiseman and his colleagues provide a cost-effective solution to this problem using a next-generation pyrosequencing approach to high-resolution MHC genotyping in various nonhuman primates, identifying both known and new MHC class I alleles.

Abstract - | Full Text - Major histocompatibility complex genotyping with massively parallel pyrosequencing | PDF (344 KB) - Major histocompatibility complex genotyping with massively parallel pyrosequencing | Supplementary information

Matrix-insensitive protein assays push the limits of biosensors in medicine - pp1327 - 1332

Richard S Gaster, Drew A Hall, Carsten H Nielsen, Sebastian J Osterfeld, Heng Yu, Kathleen E Mach, Robert J Wilson, Boris Murmann, Joseph C Liao, Sanjiv S Gambhir & Shan X Wang

doi:10.1038/nm.2032

Despite progress in the biosensor field, a platform that allows the sensitive detection of disease-specific proteins in a diverse range of clinical samples such as saliva, serum and urine has proved elusive. Here, Richard Gaster and his colleagues introduce a magnetic nanosensing protein detection platform that offers quantitative multiplex protein detection at attomolar concentrations over a large linear dynamic range and in a range of biological fluids.

Abstract - | Full Text - Matrix-insensitive protein assays push the limits of biosensors in medicine | PDF (577 KB) - Matrix-insensitive protein assays push the limits of biosensors in medicine | Supplementary information

Erratum: A selective inhibitor of the immunoproteasome subunit LMP7 blocks cytokine production and attenuates progression of experimental arthritis - p1333

Tony Muchamuel, Michael Basler, Monette A Aujay, Erika Suzuki, Khalid W Kalim, Christoph Lauer, Catherine Sylvain, Eileen R Ring, Jamie Shields, Jing Jiang, Peter Shwonek, Francesco Parlati, Susan D Demo, Mark K Bennett, Christopher J Kirk & Marcus Groettrup

doi:10.1038/nm1109-1333a

Full Text - Erratum: A selective inhibitor of the immunoproteasome subunit LMP7 blocks cytokine production and attenuates progression of experimental arthritis | PDF (54 KB) - Erratum: A selective inhibitor of the immunoproteasome subunit LMP7 blocks cytokine production and attenuates progression of experimental arthritis

Corrigendum: Baseline Ad5 serostatus does not predict Ad5 HIV vaccine–induced expansion of adenovirus-specific CD4⁺ T cells - p1333

Natalie A Hutnick, Diane G Carnathan, Sheri A Dubey, George Makedonas, Kara S Cox, Lisa Kierstead, Sarah J Ratcliffe, Michael N Robertson, Danilo R Casimiro, Hildegund C J Ertl & Michael R Betts

doi:10.1038/nm1109-1333b

Full Text - Corrigendum: Baseline Ad5 serostatus does not predict Ad5 HIV vaccine–induced expansion of adenovirus-specific CD4+ T cells | PDF (54 KB) - Corrigendum: Baseline Ad5 serostatus does not predict Ad5 HIV vaccine–induced expansion of adenovirus-specific CD4+ T cells