In the land of the monolingual - p975

doi:10.1038/nm0909-975

Translating a basic finding into a new therapy requires us to speak many languages—scientific, clinical, legal and financial. Yet most of us are hopelessly 'monolingual', a limitation that substantially slows translational research. Steps have been taken to address this problem, but a lot remains to be done.

Abstract - | Full Text - In the land of the monolingual | PDF (90 KB) - In the land of the monolingual

A change is in the wind as 'adaptive' clinical trials catch on - p977

Stu Hutson

doi:10.1038/nm0909-977

Full Text - A change is in the wind as 'adaptive' clinical trials catch on | PDF (348 KB) - A change is in the wind as 'adaptive' clinical trials catch on

Pandemic vaccine enters clinical trials - p978

Cassandra Willyard

doi:10.1038/nm0909-978a

Full Text - Pandemic vaccine enters clinical trials | PDF (74 KB) - Pandemic vaccine enters clinical trials

New plan seeks to accelerate African diagnostic capacity - p978

Melinda Wenner

doi:10.1038/nm0909-978b

Full Text - New plan seeks to accelerate African diagnostic capacity | PDF (74 KB) - New plan seeks to accelerate African diagnostic capacity

Sealants get specific - p978

Nayanah Siva

doi:10.1038/nm0909-978c

Full Text - Sealants get specific | PDF (74 KB) - Sealants get specific

New technologies promise safer sex for women - p979

Mike May

doi:10.1038/nm0909-979a

Full Text - New technologies promise safer sex for women | PDF (202 KB) - New technologies promise safer sex for women

Growing pains plague children's health study - p979

Melinda Wenner

doi:10.1038/nm0909-979b

Full Text - Growing pains plague children's health study | PDF (202 KB) - Growing pains plague children's health study

News in brief - pp980 - 981

doi:10.1038/nm0909-980

Full Text - News in brief | PDF (754 KB) - News in brief

Straight talk with...Ian Lipkin - pp982 - 983

Erica Westly

doi:10.1038/nm0909-982

Ian Lipkin, director of the Center for Infection and Immunity at Columbia University's Mailman School of Public Health, has helped identify close to 200 new viruses so far. Erica Westly spoke with Lipkin about how the viral discovery techniques he uses could help prevent future viral disease outbreaks, from swine flu to the unknown.

Abstract - | Full Text - Straight talk with...Ian Lipkin | PDF (447 KB) - Straight talk with...Ian Lipkin

Boosting our best shot - pp984 - 988

Charlotte Schubert

doi:10.1038/nm0909-984

Vaccines work by training the immune system to target pathogens, but many types of shots need added substances called adjuvants to elicit a robust response. Despite the power of adjuvants, only one, called alum, is approved in the US. Charlotte Schubert looks at recent discoveries that could translate into a wider range of adjuvants and perhaps help provide future protection against diseases ranging from malaria to H1N1 'swine' flu.

Abstract - | Full Text - Boosting our best shot | PDF (663 KB) - Boosting our best shot

Illuminating alum - p985

Charlotte Schubert

doi:10.1038/nm0909-985

Full Text - Illuminating alum | PDF (247 KB) - Illuminating alum

Swine flu agitates the adjuvant debate - pp986 - 987

Charlotte Schubert

doi:10.1038/nm0909-986

Full Text - Swine flu agitates the adjuvant debate | PDF (231 KB) - Swine flu agitates the adjuvant debate

Mouse fertility is not dependent on the CREB coactivator Crtc1 - pp989 - 990

Lionel Breuillaud, Olivier Halfon, Pierre J Magistretti, François P Pralong & Jean-René Cardinaux

doi:10.1038/nm0909-989

Full Text - Mouse fertility is not dependent on the CREB coactivator Crtc1 | PDF (182 KB) - Mouse fertility is not dependent on the CREB coactivator Crtc1 | Supplementary information

Reply to: "Mouse fertility is not dependent on the CREB coactivator Crtc1" - p991

Judith Altarejos, Naomi Goebel, Mike Conkright, Hiroshi Inoue, Jianjin Xie, Carlos Arias, Paul Sawchenko & Marc Montminy

doi:10.1038/nm0909-991a

Full Text - Reply to: "Mouse fertility is not dependent on the CREB coactivator Crtc1" | PDF (191 KB) - Reply to: "Mouse fertility is not dependent on the CREB coactivator Crtc1"

Innovating for impact: The Affordable Medicines Facility-malaria (AMFm) - p991

Olusoji Adeyi & Rifat Atun

doi:10.1038/nm0909-991b

Full Text - Innovating for impact: The Affordable Medicines Facility-malaria (AMFm) | PDF (191 KB) - Innovating for impact: The Affordable Medicines Facility-malaria (AMFm)

The vaccine-autism controversy - p992

Daniel Geschwind reviews Autism's False Prophets: Bad Science, Risky Medicine, and the Search for a Cure by Paul A. Offit

doi:10.1038/nm0909-992

Full Text - The vaccine-autism controversy | PDF (97 KB) - The vaccine-autism controversy

Blocking the path of lymphatic vessels - pp993 - 994

Mihaela Skobe & Reza Dana

doi:10.1038/nm0909-993

Identification of an endogenous inhibitor of lymphatic vessel formation provides a glimpse at how lymphatic vessel growth is restrained (pages 1023–1030). The findings might be exploited to lower transplant rejection rates.

Abstract - | Full Text - Blocking the path of lymphatic vessels | PDF (468 KB) - Blocking the path of lymphatic vessels

See also: Article by Albuquerque et al.

Two sides to cilia in cancer - pp994 - 996

Rune Toftgård

doi:10.1038/nm0909-994

The primary cilium can keep cancer at bay, or it can instigate tumor development, according to studies in mice (pages 1055–1061 and 1062–1065). The outcome depends on the nature of the initiating event, which involves signaling through the Hedgehog pathway.

Abstract - | Full Text - Two sides to cilia in cancer | PDF (267 KB) - Two sides to cilia in cancer

See also: Letter by Wong et al. | Letter by Han et al.

Connecting obesity, aging and diabetes - pp996 - 997

Rexford S. Ahima

doi:10.1038/nm0909-996

Obesity accelerates the aging of adipose tissue, a process only now beginning to come to light at the molecular level. Experiments in mice suggest that obesity increases the formation of reactive oxygen species in fat cells, shortens telomeres—and ultimately results in activation of the p53 tumor suppressor, inflammation and the promotion of insulin resistance (pages 1082–1087).

Abstract - | Full Text - Connecting obesity, aging and diabetes | PDF (664 KB) - Connecting obesity, aging and diabetes

See also: Letter by Minamino et al.

Cardiovascular biomarker questioned - p998

doi:10.1038/nm0909-998

Full Text - Cardiovascular biomarker questioned | PDF (272 KB) - Cardiovascular biomarker questioned

A safer stem cell: on guard against cancer - pp999 - 1001

Rahul Jandial & Evan Y Snyder

doi:10.1038/nm0909-999

Before stem cell therapies become mainstream, several hurdles must be overcome. One challenge is developing air-tight approaches to assure that stem cell transplantation does not give rise to tumors. Another is finding safe ways to induce pluripotency in adult stem cells, which can then be used for transplantation. In Bedside to Bench, Evan Snyder and Rahul Jandial discuss the risks of tumorigenesis in stem cell therapies, and, in Bench to Bedside, Laura Clarke and Derek van der Kooy examine new ways to induce pluripotency.

Abstract - | Full Text - A safer stem cell: on guard against cancer | PDF (197 KB) - A safer stem cell: on guard against cancer

A safer stem cell: inducing pluripotency - pp1001 - 1002

Laura Clarke & Derek van der Kooy

doi:10.1038/nm0909-1001

Full Text - A safer stem cell: inducing pluripotency | PDF (93 KB) - A safer stem cell: inducing pluripotency

Research Highlights - pp1004 - 1005

doi:10.1038/nm0909-1004

Full Text - Research Highlights | PDF (394 KB) - Research Highlights

The advancement of translational medicine—from regional challenges to global solutions - pp1006 - 1009

Salvatore Albani & Berent Prakken

doi:10.1038/nm0909-1006

Full Text - The advancement of translational medicine—from regional challenges to global solutions | PDF (404 KB) - The advancement of translational medicine—from regional challenges to global solutions

Cancer stem cells: mirage or reality? - pp1010 - 1012

Piyush B Gupta, Christine L Chaffer & Robert A Weinberg

doi:10.1038/nm0909-1010

Abstract - | Full Text - Cancer stem cells: mirage or reality? | PDF (346 KB) - Cancer stem cells: mirage or reality?

Involvement of interleukin-21 in the epidermal hyperplasia of psoriasis - pp1013 - 1015

Roberta Caruso, Elisabetta Botti, Massimiliano Sarra, Maria Esposito, Carmine Stolfi, Laura Diluvio, Maria Laura Giustizieri, Valentina Pacciani, Annamaria Mazzotta, Elena Campione, Thomas T MacDonald, Sergio Chimenti, Francesco Pallone, Antonio Costanzo & Giovanni Monteleone

doi:10.1038/nm.1995

Giovanni Monteleone and his colleagues show that the T cell-derived cytokine interleukin-21 is a new potential therapeutic target for psoriasis. Interleukin-21 seems to act directly on keratinocytes, stimulating them to proliferate and causing epidermal hyperplasia.

Abstract - | Full Text - Involvement of interleukin-21 in the epidermal hyperplasia of psoriasis | PDF (394 KB) - Involvement of interleukin-21 in the epidermal hyperplasia of psoriasis | Supplementary information

A human colonic commensal promotes colon tumorigenesis via activation of T helper type 17 T cell responses - pp1016 - 1022

Shaoguang Wu, Ki-Jong Rhee, Emilia Albesiano, Shervin Rabizadeh, Xinqun Wu, Hung-Rong Yen, David L Huso, Frederick L Brancati, Elizabeth Wick, Florencia McAllister, Franck Housseau, Drew M Pardoll & Cynthia L Sears

doi:10.1038/nm.2015

Enterotoxigenic Bacteroides fragilis, a bacterium from the intestinal flora, may promote colon tumor formation through a pathway that involves Stat3 expression and T helper type 17 immune responses.

Abstract - | Full Text - A human colonic commensal promotes colon tumorigenesis via activation of T helper type 17 T cell responses | PDF (1,099 KB) - A human colonic commensal promotes colon tumorigenesis via activation of T helper type 17 T cell responses | Supplementary information

Alternatively spliced vascular endothelial growth factor receptor-2 is an essential endogenous inhibitor of lymphatic vessel growth - pp1023 - 1030

Romulo J C Albuquerque, Takahiko Hayashi, Won Gil Cho, Mark E Kleinman, Sami Dridi, Atsunobu Takeda, Judit Z Baffi, Kiyoshi Yamada, Hiroki Kaneko, Martha G Green, Joe Chappell, Jörg Wilting, Herbert A Weich, Satoru Yamagami, Shiro Amano, Nobuhisa Mizuki, Jonathan S Alexander, Martha L Peterson, Rolf A Brekken, Masanori Hirashima, Seema Capoor, Tomohiko Usui, Balamurali K Ambati & Jayakrishna Ambati

doi:10.1038/nm.2018

Although endogenous inhibitors of blood vessel growth have been studied extensively, specific inhibitors of lymphatic vessel growth have not been identified. Albuquerque et al. now identify truncated, secreted versions of mouse and human VEGFR-2 receptors generated by alternative splicing. The mouse protein acts as an endogenous inhibitor of lymphatic vessel growth in the cornea and skin, and its administration had therapeutic effects in mouse models of corneal injury and transplantation.

Abstract - | Full Text - Alternatively spliced vascular endothelial growth factor receptor-2 is an essential endogenous inhibitor of lymphatic vessel growth | PDF (1,215 KB) - Alternatively spliced vascular endothelial growth factor receptor-2 is an essential endogenous inhibitor of lymphatic vessel growth | Supplementary information

See also: News and Views by Skobe & Dana

Pericyte contraction induced by oxidative-nitrative stress impairs capillary reflow despite successful opening of an occluded cerebral artery - pp1031 - 1037

Muge Yemisci, Yasemin Gursoy-Ozdemir, Atay Vural, Alp Can, Kamil Topalkara & Turgay Dalkara

doi:10.1038/nm.2022

Ischemia causes pericytes on brain microvessels to contract, obstructing erythrocyte transit even after blood flow is restored. This contraction, which depends on the production of oxygen and nitrogen radicals, represents a novel pathophysiological mechanism in stroke.

Abstract - | Full Text - Pericyte contraction induced by oxidative-nitrative stress impairs capillary reflow despite successful opening of an occluded cerebral artery | PDF (1,140 KB) - Pericyte contraction induced by oxidative-nitrative stress impairs capillary reflow despite successful opening of an occluded cerebral artery | Supplementary information

A granulocyte-macrophage colony–stimulating factor and interleukin-15 fusokine induces a regulatory B cell population with immune suppressive properties - pp1038 - 1045

Moutih Rafei, Jeremy Hsieh, Simone Zehntner, MengYang Li, Kathy Forner, Elena Birman, Marie-Noëlle Boivin, Yoon Kow Young, Claude Perreault & Jacques Galipeau

doi:10.1038/nm.2003

Suppression of the immune system could block autoimmune disease pathogenesis. Here Jacques Galipeau and his colleagues report that a fusion protein of two cytokines can induce immunosuppressive regulatory B cells. Transferring these cells into a mouse model of multiple sclerosis reduces disease in the mice.

Abstract - | Full Text - A granulocyte-macrophage colony–stimulating factor and interleukin-15 fusokine induces a regulatory B cell population with immune suppressive properties | PDF (1,324 KB) - A granulocyte-macrophage colony–stimulating factor and interleukin-15 fusokine induces a regulatory B cell population with immune suppressive properties

Impaired Wnt–-catenin signaling disrupts adult renal homeostasis and leads to cystic kidney ciliopathy - pp1046 - 1054

Madeline A Lancaster, Carrie M Louie, Jennifer L Silhavy, Louis Sintasath, Marvalyn DeCambre, Sanjay K Nigam, Karl Willert & Joseph G Gleeson

doi:10.1038/nm.2010

Canonical Wnt signaling is known to be crucial in embryonic organ development. Joseph Gleeson and his colleagues now report that it is also important in the adult homeostasis of the kidney, especially after injury, and that disruption of this signaling pathway results in cystic kidney disease.

Abstract - | Full Text - Impaired Wnt–-catenin signaling disrupts adult renal homeostasis and leads to cystic kidney ciliopathy | PDF (2,413 KB) - Impaired Wnt–-catenin signaling disrupts adult renal homeostasis and leads to cystic kidney ciliopathy | Supplementary information

Primary cilia can both mediate and suppress Hedgehog pathway–dependent tumorigenesis - pp1055 - 1061

Sunny Y Wong, Allen D Seol, Po-Lin So, Alexandre N Ermilov, Christopher K Bichakjian, Ervin H Epstein Jr, Andrzej A Dlugosz & Jeremy F Reiter

doi:10.1038/nm.2011

These two studies show that primary cilia can either mediate or suppress tumorigenesis in models of basal cell carcinoma and medulloblastoma, respectively, depending on the nature of the initial oncogenic event (pages 994–996) and (pages 1062–1065).

First Paragraph - | Full Text - Primary cilia can both mediate and suppress Hedgehog pathway–dependent tumorigenesis | PDF (1,363 KB) - Primary cilia can both mediate and suppress Hedgehog pathway–dependent tumorigenesis | Supplementary information

See also: News and Views by Toftgård | Letter by Han et al.

Dual and opposing roles of primary cilia in medulloblastoma development - pp1062 - 1065

Young-Goo Han, Hong Joo Kim, Andrzej A Dlugosz, David W Ellison, Richard J Gilbertson & Arturo Alvarez-Buylla

doi:10.1038/nm.2020

These two studies show that primary cilia can either mediate or suppress tumorigenesis in models of basal cell carcinoma and medulloblastoma, respectively, depending on the nature of the initial oncogenic event (pages 994–996) and (pages 1055–1061).

First Paragraph - | Full Text - Dual and opposing roles of primary cilia in medulloblastoma development | PDF (613 KB) - Dual and opposing roles of primary cilia in medulloblastoma development | Supplementary information

See also: News and Views by Toftgård | Letter by Wong et al.

Interferon regulatory factor-8 regulates bone metabolism by suppressing osteoclastogenesis - pp1066 - 1071

Baohong Zhao, Masamichi Takami, Atsushi Yamada, Xiaogu Wang, Takako Koga, Xiaoyu Hu, Tomohiko Tamura, Keiko Ozato, Yongwon Choi, Lionel B Ivashkiv, Hiroshi Takayanagi & Ryutaro Kamijo

doi:10.1038/nm.2007

Dysregulation of osteoclasts, the cells that chew up bone, can lead to severe bone loss. Although many positive regulators of the differentiation of this cell type have been identified, few negative regulators have. Now, Masamichi Takami and colleagues have identified IRF-8 as an inhibitor of osteoclast formation and explore its role in disease.

First Paragraph - | Full Text - Interferon regulatory factor-8 regulates bone metabolism by suppressing osteoclastogenesis | PDF (1,215 KB) - Interferon regulatory factor-8 regulates bone metabolism by suppressing osteoclastogenesis | Supplementary information

Syndecan-4 regulates ADAMTS-5 activation and cartilage breakdown in osteoarthritis - pp1072 - 1076

Frank Echtermeyer, Jessica Bertrand, Rita Dreier, Ingmar Meinecke, Katja Neugebauer, Martin Fuerst, Yun Jong Lee, Yeong Wook Song, Christine Herzog, Gregor Theilmeier & Thomas Pap

doi:10.1038/nm.1998

The degenerative joint disease osteoarthritis is known to involve the activation of the protease ADAMTS-5. Now, Frank Echtermeyer and his colleagues have shown that the transmembrane proteoglycan syndecan-4 is responsible for this activation. They also show that genetic deletion of syndecan-4, or inhibition with a blocking antibody, reduces disease progression in a mouse model.

First Paragraph - | Full Text - Syndecan-4 regulates ADAMTS-5 activation and cartilage breakdown in osteoarthritis | PDF (768 KB) - Syndecan-4 regulates ADAMTS-5 activation and cartilage breakdown in osteoarthritis | Supplementary information

NADPH oxidase-4 mediates myofibroblast activation and fibrogenic responses to lung injury - pp1077 - 1081

Louise Hecker, Ragini Vittal, Tamara Jones, Rajesh Jagirdar, Tracy R Luckhardt, Jeffrey C Horowitz, Subramaniam Pennathur, Fernando J Martinez & Victor J Thannickal

doi:10.1038/nm.2005

The mechanisms that lead to idiopathic pulmonary fibrosis, or lung scarring, is not clear. Victor Thannickal and his colleagues have now provided further insight by showing that induction of NOX4, an enzyme that creates reactive oxygen species, is required for the progression of the disease. Their findings suggest NOX4 as a potential target to treat this common ailment that currently has no proven treatment options.

Abstract - | Full Text - NADPH oxidase-4 mediates myofibroblast activation and fibrogenic responses to lung injury | PDF (1,013 KB) - NADPH oxidase-4 mediates myofibroblast activation and fibrogenic responses to lung injury | Supplementary information

A crucial role for adipose tissue p53 in the regulation of insulin resistance - pp1082 - 1087

Tohru Minamino, Masayuki Orimo, Ippei Shimizu, Takeshige Kunieda, Masataka Yokoyama, Takashi Ito, Aika Nojima, Akira Nabetani, Yuichi Oike, Hisahiro Matsubara, Fuyuki Ishikawa & Issei Komuro

doi:10.1038/nm.2014

A role for cell senescence and p53 in the development of insulin resistance (or prediabetes) has been obscure. Issei Komuro and colleagues now show that premature cell senescence occurs in the adipose tissue of obese mice and humans and that genetic deficiency of p53 is sufficient to prevent insulin resistance in mouse models of obesity, suggesting a new target to treat diabetes.

First Paragraph - | Full Text - A crucial role for adipose tissue p53 in the regulation of insulin resistance | PDF (587 KB) - A crucial role for adipose tissue p53 in the regulation of insulin resistance | Supplementary information

See also: News and Views by Ahima

A rapid and efficient single-cell manipulation method for screening antigen-specific antibody–secreting cells from human peripheral blood - pp1088 - 1092

Aishun Jin, Tatsuhiko Ozawa, Kazuto Tajiri, Tsutomu Obata, Sachiko Kondo, Koshi Kinoshita, Shinichi Kadowaki, Kazuo Takahashi, Toshiro Sugiyama, Hiroyuki Kishi & Atsushi Muraguchi

doi:10.1038/nm.1966

Jin and colleagues introduce a new chip-based system for the rapid identification and isolation of single antigen-specific antibody–secreting cells from human peripheral blood lymphocytes. The approach can be used to detect antibody-secreting cells for multiple antigens on the same chip and should have advantages over current technologies for isolating and producing human monoclonal antibodies of clinical significance.

Abstract - | Full Text - A rapid and efficient single-cell manipulation method for screening antigen-specific antibody–secreting cells from human peripheral blood | PDF (603 KB) - A rapid and efficient single-cell manipulation method for screening antigen-specific antibody–secreting cells from human peripheral blood | Supplementary information

Erratum: GOAT links dietary lipids with the endocrine control of energy balance - p1093

Henriette Kirchner, Jesus A Gutierrez, Patricia J Solenberg, Paul T Pfluger, Traci A Czyzyk, Jill A Willency, Annette Schürmann, Hans-Georg Joost, Ronald J Jandacek, John E Hale, Mark L Heiman & Matthias H Tschöp

doi:10.1038/nm0909-1093a

Full Text - Erratum: GOAT links dietary lipids with the endocrine control of energy balance | PDF (56 KB) - Erratum: GOAT links dietary lipids with the endocrine control of energy balance

Corrigendum: Aldosterone impairs vascular reactivity by decreasing glucose-6-phosphate dehydrogenase activity - p1093

Jane A Leopold, Aamir Dam, Bradley A Maron, Anne W Scribner, Ronglih Liao, Diane E Handy, Robert C Stanton, Bertram Pitt & Joseph Loscalzo

doi:10.1038/nm0909-1093b

Full Text - Corrigendum: Aldosterone impairs vascular reactivity by decreasing glucose-6-phosphate dehydrogenase activity | PDF (56 KB) - Corrigendum: Aldosterone impairs vascular reactivity by decreasing glucose-6-phosphate dehydrogenase activity