Winds of change, clouds of smoke - p991

doi:10.1038/nm1008-991

Elections may be won on national issues, but the domestic concerns of a superpower have global ramifications, and the science policy of the next US administration will be no exception.

Abstract - | Full Text - Winds of change, clouds of smoke | PDF (95 KB) - Winds of change, clouds of smoke

Revamped guidelines aim to keep pace with stem cell advances - p993

Stu Hutson

doi:10.1038/nm1008-993

Full Text - Revamped guidelines aim to keep pace with stem cell advances | PDF (254 KB) - Revamped guidelines aim to keep pace with stem cell advances

Experts point to concerning disparities within MD-PhD programs - p994

Daniel Cressey

doi:10.1038/nm1008-994a

Full Text - Experts point to concerning disparities within MD-PhD programs | PDF (131 KB) - Experts point to concerning disparities within MD-PhD programs

Success of blood-sugar monitors puts artificial pancreas in reach - p994

Meredith Wadman

doi:10.1038/nm1008-994b

Full Text - Success of blood-sugar monitors puts artificial pancreas in reach | PDF (131 KB) - Success of blood-sugar monitors puts artificial pancreas in reach

Patient-based site tracks drug responses - p995

Genevive Bjorn

doi:10.1038/nm1008-995a

Full Text - Patient-based site tracks drug responses | PDF (187 KB) - Patient-based site tracks drug responses

Condom ringtone catches on - p995

TV Padma

doi:10.1038/nm1008-995b

Full Text - Condom ringtone catches on | PDF (187 KB) - Condom ringtone catches on

Multi-million dollar grants give 'Broadies' a lasting home - p996

Heidi Ledford

doi:10.1038/nm1008-996a

Full Text - Multi-million dollar grants give 'Broadies' a lasting home | PDF (289 KB) - Multi-million dollar grants give 'Broadies' a lasting home

Barriers set up to protect genome databases - p996

Genevive Bjorn

doi:10.1038/nm1008-996b

Full Text - Barriers set up to protect genome databases | PDF (289 KB) - Barriers set up to protect genome databases

California aims to crack down on animal rights extremists - p997

Coco Ballantyne

doi:10.1038/nm1008-997

Full Text - California aims to crack down on animal rights extremists | PDF (315 KB) - California aims to crack down on animal rights extremists

News in brief - pp998 - 999

doi:10.1038/nm1008-998

Full Text - News in brief | PDF (609 KB) - News in brief

2008 US ELECTION SPECIAL

The 2008 US presidential election: A look at the candidates - p1000

doi:10.1038/nm1008-1000

Full Text - The 2008 US presidential election: A look at the candidates | PDF (301 KB) - The 2008 US presidential election: A look at the candidates

2008 US ELECTION SPECIAL

A state-by-state look at biomedical issues - p1001

doi:10.1038/nm1008-1001

Full Text - A state-by-state look at biomedical issues | PDF (176 KB) - A state-by-state look at biomedical issues

2008 US ELECTION SPECIAL

The lobbying landscape and beyond: 15 groups to know - pp1002 - 1003

doi:10.1038/nm1008-1002

Full Text - The lobbying landscape and beyond: 15 groups to know | PDF (658 KB) - The lobbying landscape and beyond: 15 groups to know

2008 US ELECTION SPECIAL

10 influential people to watch in biomedical policy - pp1004 - 1005

doi:10.1038/nm1008-1004

Full Text - 10 influential people to watch in biomedical policy | PDF (393 KB) - 10 influential people to watch in biomedical policy

Straight talk with...Charles Grassley - pp1006 - 1007

doi:10.1038/nm1008-1006

What would a trim 75-year-old grain farmer have to say about drug safety and the payments given to medical researchers by drug companies? Lots, if he happens to be Charles Grassley, who has represented the state of Iowa in the US Senate since 1980. As the senior Republican on the Senate's finance and judiciary committees, he has carved out a role as a relentless watchdog who acts as a magnet for whistleblowers in government agencies ranging from the US Department of Defense to the Federal Bureau of Investigation (FBI).
In the last several years, Grassley has set his investigative sights on issues relating to medicine. A leading critic of the Food and Drug Administration (FDA) since the surprise withdrawal from the market of Merck's painkiller Vioxx in 2004, Grassley is now focusing on university researchers funded by the National Institutes of Health (NIH) who haven't been properly reporting income from drug companies. Meredith Wadman asked the senator what he hopes to achieve through his investigations.

Abstract - | Full Text - Straight talk with...Charles Grassley | PDF (259 KB) - Straight talk with...Charles Grassley

SNO-hemoglobin and hypoxic vasodilation - pp1008 - 1009

Jonathan S Stamler, David J Singel & Claude A Piantadosi

doi:10.1038/nm1008-1008

Full Text - SNO-hemoglobin and hypoxic vasodilation | PDF (90 KB) - SNO-hemoglobin and hypoxic vasodilation

SNO-hemoglobin and hypoxic vasodilation - p1009

Lisa A Palmer, Allan Doctor & Benjamin Gaston

doi:10.1038/nm1008-1009a

Full Text - SNO-hemoglobin and hypoxic vasodilation | PDF (79 KB) - SNO-hemoglobin and hypoxic vasodilation

SNO-hemoglobin and hypoxic vasodilation - pp1009 - 1010

Rakesh Patel & Tim Townes

doi:10.1038/nm1008-1009b

Full Text - SNO-hemoglobin and hypoxic vasodilation | PDF (92 KB) - SNO-hemoglobin and hypoxic vasodilation

Experimental use of nonhuman primates is not a simple problem - p1011

Chris Martin

doi:10.1038/nm1008-1011a

Full Text - Experimental use of nonhuman primates is not a simple problem | PDF (75 KB) - Experimental use of nonhuman primates is not a simple problem

Experimental use of nonhuman primates is not a simple problem - pp1011 - 1012

Jarrod Bailey, Theodora Capaldo, Kathleen Conlee, Michelle Thew & John Pippin

doi:10.1038/nm1008-1011b

Full Text - Experimental use of nonhuman primates is not a simple problem | PDF (90 KB) - Experimental use of nonhuman primates is not a simple problem

Experimental use of nonhuman primates is not a simple problem - p1012

Niall Shanks & Ray Greek

doi:10.1038/nm1008-1012a

Full Text - Experimental use of nonhuman primates is not a simple problem | PDF (78 KB) - Experimental use of nonhuman primates is not a simple problem

Experimental use of nonhuman primates is not a simple problem - pp1012 - 1013

doi:10.1038/nm1008-1012b

Full Text - Experimental use of nonhuman primates is not a simple problem | PDF (85 KB) - Experimental use of nonhuman primates is not a simple problem

The commercialism of academic research - p1014

Donald P McDonnell reviews Science for Sale: The Perils, Rewards and Delusions of Campus Capitalism by Daniel S. Greenberg

doi:10.1038/nm1008-1014

Full Text - The commercialism of academic research | PDF (90 KB) - The commercialism of academic research

Getting to the core of atherosclerosis - pp1015 - 1016

Nancy R Webb

doi:10.1038/nm1008-1015

For years, researchers have debated whether the enzyme lipoprotein-associated phospholipase A₂ (Lp-PLA₂), produced by inflammatory cells, is a 'good guy' or 'bad guy' in atherosclerosis. Work in pigs provides strong support for the view that Lp-PLA₂ promotes the formation of atherosclerotic lesions and dangerous, unstable atherosclerotic plaques (pages 1059–1066).

Abstract - | Full Text - Getting to the core of atherosclerosis | PDF (246 KB) - Getting to the core of atherosclerosis

See also: Article by Wilensky et al.

Immune alteration fends off AIDS - pp1016 - 1018

Karen O'Connell & Robert F Siliciano

doi:10.1038/nm1008-1016

Comparative studies of the immune response to simian immunodeficiency virus in two nonhuman primate species provide insight into a central aspect of HIV infection—the ability of the virus to cause chronic activation of the immune system (pages 1077–1087).

Abstract - | Full Text - Immune alteration fends off AIDS | PDF (625 KB) - Immune alteration fends off AIDS

See also: Article by Mandl et al.

Autoantibodies vex the vasculature - pp1018 - 1019

Cees GM Kallenberg, Coen A Stegeman & Peter Heeringa

doi:10.1038/nm1008-1018

Infections with fimbriated bacteria may trigger autoimmunity and cause a form of severe vasculitis that affects capillaries in the kidney and that can destroy the organ (pages 1088–1096).

Abstract - | Full Text - Autoantibodies vex the vasculature | PDF (600 KB) - Autoantibodies vex the vasculature

See also: Article by Kain et al.

Portal to Alzheimer's disease - pp1020 - 1021

Anatoly A Starkov & Flint M Beal

doi:10.1038/nm1008-1020

Genetic inactivation of the mitochondrial self-destruction mechanism improves cognition in a mouse model of Alzheimer's disease (pages 1097–1105).

Abstract - | Full Text - Portal to Alzheimer's disease | PDF (2,093 KB) - Portal to Alzheimer's disease

See also: Article by Du et al.

Community corner - p1022

doi:10.1038/nm1008-1022

Full Text - Community corner | PDF (178 KB) - Community corner

Common origins of lung cancer and COPD - pp1023 - 1024

A McGarry Houghton, Majd Mouded & Steven D Shapiro

doi:10.1038/nm1008-1023

Smoke is a solid. Whether from cigarettes, cooking fires or other sources, it is comprised of tiny particles that injure the lung and can lead to lung cancer and chronic obstructive pulmonary disorder, characterized by laborious breathing. Steven D. Shapiro and his colleagues take a look at imaging data in people suggesting that these two conditions have more in common mechanistically than was previously thought. Both diseases seem to stem in part from the ability of inhaled particles to trigger inflammation, a process examined by Robert M. Senior and his colleagues.

Abstract - | Full Text - Common origins of lung cancer and COPD | PDF (2,384 KB) - Common origins of lung cancer and COPD

Smoke particulates stress lung cells - pp1024 - 1025

Tracy L Adair-Kirk, Jeffrey J Atkinson & Robert M Senior

doi:10.1038/nm1008-1024

Smoke is a solid. Whether from cigarettes, cooking fires or other sources, it is comprised of tiny particles that injure the lung and can lead to lung cancer and chronic obstructive pulmonary disorder, characterized by laborious breathing. Steven D. Shapiro and his colleagues take a look at imaging data in people suggesting that these two conditions have more in common mechanistically than was previously thought. Both diseases seem to stem in part from the ability of inhaled particles to trigger inflammation, a process examined by Robert M. Senior and his colleagues.

Abstract - | Full Text - Smoke particulates stress lung cells | PDF (156 KB) - Smoke particulates stress lung cells

Research highlights - pp1026 - 1027

doi:10.1038/nm1008-1026

Full Text - Research highlights | PDF (296 KB) - Research highlights

2008 Albert Lasker Medical Research Awards

Exuberant unpredictability: sine qua non for priceless and prizeworthy biomedical research - pp1029 - 1032

Joseph L Goldstein

doi:10.1038/nm1008-1029

Full Text - Exuberant unpredictability: sine qua non for priceless and prizeworthy biomedical research | PDF (574 KB) - Exuberant unpredictability: sine qua non for priceless and prizeworthy biomedical research

2008 Albert Lasker Medical Research Awards

Three catalytic lives linked by the Lasker Awards - pp1033 - 1035

Jordan U Gutterman & Neen Hunt

doi:10.1038/nm1008-1033

Full Text - Three catalytic lives linked by the Lasker Awards | PDF (396 KB) - Three catalytic lives linked by the Lasker Awards

2008 Albert Lasker Medical Research Awards

The evolution of our thinking about microRNAs - pp1036 - 1040

Victor Ambros

doi:10.1038/nm1008-1036

Full Text - The evolution of our thinking about microRNAs | PDF (352 KB) - The evolution of our thinking about microRNAs

2008 Albert Lasker Medical Research Awards

The perfect storm of tiny RNAs - pp1041 - 1045

Gary Ruvkun

doi:10.1038/nm1008-1041

Full Text - The perfect storm of tiny RNAs | PDF (159 KB) - The perfect storm of tiny RNAs

2008 Albert Lasker Medical Research Awards

Of maize and men, or peas and people: case histories to justify plants and other model systems - pp1046 - 1049

David Baulcombe

doi:10.1038/nm1008-1046

Full Text - Of maize and men, or peas and people: case histories to justify plants and other model systems | PDF (430 KB) - Of maize and men, or peas and people: case histories to justify plants and other model systems

2008 Albert Lasker Medical Research Awards

A gift from nature: the birth of the statins - pp1050 - 1052

Akira Endo

doi:10.1038/nm1008-1050

Full Text - A gift from nature: the birth of the statins | PDF (340 KB) - A gift from nature: the birth of the statins

2008 Albert Lasker Medical Research Awards

I never met a microbe I didn't like - pp1053 - 1057

Stanley Falkow

doi:10.1038/nm1008-1053

Full Text - I never met a microbe I didn't like | PDF (696 KB) - I never met a microbe I didn't like

Inhibition of lipoprotein-associated phospholipase A₂ reduces complex coronary atherosclerotic plaque development - pp1059 - 1066

Robert L Wilensky, Yi Shi, Emile R Mohler, III, Damir Hamamdzic, Mark E Burgert, Jun Li, Anthony Postle, Robert S Fenning, James G Bollinger, Bryan E Hoffman, Daniel J Pelchovitz, Jisheng Yang, Rosanna C Mirabile, Christine L Webb, LeFeng Zhang, Ping Zhang, Michael H Gelb, Max C Walker, Andrew Zalewski & Colin H Macphee

doi:10.1038/nm.1870

Although increased levels of lipoprotein-associated phospholipase A2 (Lp-PLA2) have been associated with cardiac disease, whether this enzyme has a causal role in the development of atherosclerosis has not been clear. Wilensky et al. now show in a pig model of atherosclerosis that a selective Lp-PLA2 inhibitor reduces progression to complex atherosclerotic lesion formation, an effect that is associated with decreased infiltration of inflammatory cells into the lesions. These results support the use of Lp-PLA2 inhibitors for the treatment of atherosclerotic cardiovascular disease.

Abstract - | Full Text - Inhibition of lipoprotein-associated phospholipase A2 reduces complex coronary atherosclerotic plaque development | PDF (708 KB) - Inhibition of lipoprotein-associated phospholipase A2 reduces complex coronary atherosclerotic plaque development | Supplementary information

See also: News and Views by Webb

The succinate receptor GPR91 in neurons has a major role in retinal angiogenesis - pp1067 - 1076

Przemyslaw Sapieha, Mirna Sirinyan, David Hamel, Karine Zaniolo, Jean-Sébastien Joyal, Jang-Hyeon Cho, Jean-Claude Honoré, Elsa Kermorvant-Duchemin, Daya R Varma, Sophie Tremblay, Martin Leduc, Lenka Rihakova, Pierre Hardy, William H Klein, Xiuqian Mu, Orval Mamer, Pierre Lachapelle, Adriana Di Polo, Christian Beauséjour, Gregor Andelfinger, Grant Mitchell, Florian Sennlaub & Sylvain Chemtob

doi:10.1038/nm.1873

The mechanisms that control blood vessel formation are incompletely understood. Sylvain Chemtob and his colleagues now find that blood vessel formation in mouse and rat retinas is controlled by succinate generated during hypoxic and ischemic conditions. Succinate acting through its receptor, GPR91, on retinal ganglion neurons, triggers secretion of canonical proangiogenic factors and the formation of new blood vessels to reinstate adequate tissue supply. This work also identifies GPR91 as a potential therapeutic target for the treatment of ischemic retinopathies.

Abstract - | Full Text - The succinate receptor GPR91 in neurons has a major role in retinal angiogenesis | PDF (1,246 KB) - The succinate receptor GPR91 in neurons has a major role in retinal angiogenesis | Supplementary information

Divergent TLR7 and TLR9 signaling and type I interferon production distinguish pathogenic and nonpathogenic AIDS virus infections - pp1077 - 1087

Judith N Mandl, Ashley P Barry, Thomas H Vanderford, Natalia Kozyr, Rahul Chavan, Sara Klucking, Franck J Barrat, Robert L Coffman, Silvija I Staprans & Mark B Feinberg

doi:10.1038/nm.1871

Unlike HIV-infected humans or SIV-infected rhesus macaques, natural monkey hosts for SIV do not show immune activation or progress to AIDS, even though they have high viral loads after infection. Differences in the innate immune response in these monkeys may provide a clue as to why they remain healthy.

Abstract - | Full Text - Divergent TLR7 and TLR9 signaling and type I interferon production distinguish pathogenic and nonpathogenic AIDS virus infections | PDF (709 KB) - Divergent TLR7 and TLR9 signaling and type I interferon production distinguish pathogenic and nonpathogenic AIDS virus infections | Supplementary information

See also: News and Views by O'Connell & Siliciano

Molecular mimicry in pauci-immune focal necrotizing glomerulonephritis - pp1088 - 1096

Renate Kain, Markus Exner, Ricarda Brandes, Reinhard Ziebermayr, Dawn Cunningham, Carol A Alderson, Agnes Davidovits, Ingrid Raab, Renate Jahn, Oliver Ashour, Susanne Spitzauer, Gere Sunder-Plassmann, Minoru Fukuda, Per Klemm, Andrew J Rees & Dontscho Kerjaschki

doi:10.1038/nm.1874

Pauci-immune crescentic glomerulonephritis—an inflammatory disease of the kidneys— may be triggered by bacterial infection. Kain et al. show that almost all individuals with this disease have auto-antibodies to the membrane protein LAMP-2. These antibodies cross-react with the bacterial adhesion FimH, and immunization with FimH causes disease in rats.

Abstract - | Full Text - Molecular mimicry in pauci-immune focal necrotizing glomerulonephritis | PDF (995 KB) - Molecular mimicry in pauci-immune focal necrotizing glomerulonephritis | Supplementary information

See also: News and Views by Kallenberg et al.

Cyclophilin D deficiency attenuates mitochondrial and neuronal perturbation and ameliorates learning and memory in Alzheimer's disease - pp1097 - 1105

Heng Du, Lan Guo, Fang Fang, Doris Chen, Alexander A Sosunov, Guy M McKhann, Yilin Yan, Chunyu Wang, Hong Zhang, Jeffery D Molkentin, Frank J Gunn-Moore, Jean Paul Vonsattel, Ottavio Arancio, John Xi Chen & Shi Du Yan

doi:10.1038/nm.1868

Mitochondrial dysfunction has been described in Alzheimer's disease, but how it is induced has remained unclear. Shi Du Yan and her colleagues find that a neurotoxic amyloid protein associated with the disease binds a mitochondrial protein called cyclophilin D and causes neuron death. The authors show that Alzheimer's disease model mice that lack cyclophilin D show improvements in learning and memory.

Abstract - | Full Text - Cyclophilin D deficiency attenuates mitochondrial and neuronal perturbation and ameliorates learning and memory in Alzheimer's disease | PDF (762 KB) - Cyclophilin D deficiency attenuates mitochondrial and neuronal perturbation and ameliorates learning and memory in Alzheimer's disease | Supplementary information

See also: News and Views by Starkov & Beal

Glutaminyl cyclase inhibition attenuates pyroglutamate A and Alzheimer's disease–like pathology - pp1106 - 1111

Stephan Schilling, Ulrike Zeitschel, Torsten Hoffmann, Ulrich Heiser, Mike Francke, Astrid Kehlen, Max Holzer, Birgit Hutter-Paier, Manuela Prokesch, Manfred Windisch, Wolfgang Jagla, Dagmar Schlenzig, Christiane Lindner, Thomas Rudolph, Gunter Reuter, Holger Cynis, Dirk Montag, Hans-Ulrich Demuth & Steffen Rossner

doi:10.1038/nm.1872

Some A peptides contain pyroglutamate modifications that affect the aggregation properties of these peptides. The authors find that the enzyme glutaminyl cyclase is responsible for this pyroglutamate modification. When they inhibit the enzyme in Alzheimer's model mice, fewer plaques form in the brain, and some measures of learning and memory are improved.

First Paragraph - | Full Text - Glutaminyl cyclase inhibition attenuates pyroglutamate A and Alzheimer's disease–like pathology | PDF (450 KB) - Glutaminyl cyclase inhibition attenuates pyroglutamate A and Alzheimer's disease–like pathology | Supplementary information

The Creb1 coactivator Crtc1 is required for energy balance and fertility - pp1112 - 1117

Judith Y Altarejos, Naomi Goebel, Michael D Conkright, Hiroshi Inoue, Jianxin Xie, Carlos M Arias, Paul E Sawchenko & Marc Montminy

doi:10.1038/nm.1866

First Paragraph - | Full Text - The Creb1 coactivator Crtc1 is required for energy balance and fertility | PDF (764 KB) - The Creb1 coactivator Crtc1 is required for energy balance and fertility | Supplementary information

Bortezomib-induced enzyme-targeted radiation therapy in herpesvirus-associated tumors - pp1118 - 1122

De-Xue Fu, Yvette Tanhehco, Jianmeng Chen, Catherine A Foss, James J Fox, Ja-Mun Chong, Robert F Hobbs, Masashi Fukayama, George Sgouros, Jeanne Kowalski, Martin G Pomper & Richard F Ambinder

doi:10.1038/nm.1864

De-Xue Fu et al. present a novel approach to radiotherapy of herpesvirus-associated tumors by first inducing the expression of viral thymidine kinase by pretreatment with bortezomib and then by administering a radiopharmaceutical that targets the viral enzyme. The authors show that this approach is effective in lymphoid and epithelial malignancies in several xenograft mouse models of human tumors.

First Paragraph - | Full Text - Bortezomib-induced enzyme-targeted radiation therapy in herpesvirus-associated tumors | PDF (313 KB) - Bortezomib-induced enzyme-targeted radiation therapy in herpesvirus-associated tumors | Supplementary information

Chemical control of protein stability and function in living mice - pp1123 - 1127

Laura A Banaszynski, Mark A Sellmyer, Christopher H Contag, Thomas J Wandless & Steve H Thorne

doi:10.1038/nm.1754

Banaszynski et al. combine genetic manipulation with small-molecule regulation to produce rapid, reversible and tunable regulation of protein expression in vivo. The approach builds on earlier work showing that fusion of a destabilizing domain to a gene of interest confers instability to the expressed protein. Degradation of the protein is then prevented by subsequent addition of the cell-permeable stabilizing ligand, Shield-1, which binds specifically to the destabilizing domains. Three in vivo applications of the technology in mice are described.

Abstract - | Full Text - Chemical control of protein stability and function in living mice | PDF (298 KB) - Chemical control of protein stability and function in living mice | Supplementary information

Corrigendum: RPN2 gene confers docetaxel resistance in breast cancer - p1128

Kimi Honma, Kyoko Iwao-Koizumi, Fumitaka Takeshita, Yusuke Yamamoto, Teruhiko Yoshida, Kazuto Nishio, Shunji Nagahara, Kikuya Kato & Takahiro Ochiya

doi:10.1038/nm1008-1128

Full Text - Corrigendum: RPN2 gene confers docetaxel resistance in breast cancer | PDF (49 KB) - Corrigendum: RPN2 gene confers docetaxel resistance in breast cancer