When less is not more - pp791 - 792

doi:10.1038/nm0808-791

Critics of experimentation in nonhuman primates have used a variety of arguments to defend their views. Yet some of those arguments can be used to advocate the use of these animals in biomedical research.

Abstract - | Full Text - When less is not more | PDF (102 KB) - When less is not more

Mystery of preterm birth prompts search for better models - p793

Coco Ballantyne

doi:10.1038/nm0808-793a

Full Text - Mystery of preterm birth prompts search for better models | PDF (179 KB) - Mystery of preterm birth prompts search for better models

One egg is best - p793

Coco Ballantyne

doi:10.1038/nm0808-793b

Full Text - One egg is best | PDF (179 KB) - One egg is best

Researchers see a need for speed in EU trial approvals - p794

Daniel Cressey

doi:10.1038/nm0808-794a

Full Text - Researchers see a need for speed in EU trial approvals | PDF (218 KB) - Researchers see a need for speed in EU trial approvals

Synonym swapping to make vaccines - p794

Coco Ballantyne

doi:10.1038/nm0808-794b

Full Text - Synonym swapping to make vaccines | PDF (218 KB) - Synonym swapping to make vaccines

Experts urge a more measured look at antioxidants - p795

Stu Hutson

doi:10.1038/nm0808-795a

Full Text - Experts urge a more measured look at antioxidants | PDF (122 KB) - Experts urge a more measured look at antioxidants

National Cancer Institute helps businesses cross 'the valley of death' - p795

Prashant Nair

doi:10.1038/nm0808-795b

Full Text - National Cancer Institute helps businesses cross 'the valley of death' | PDF (122 KB) - National Cancer Institute helps businesses cross 'the valley of death'

A testing approach based on tiny doses still awaits big results - p796

Amy Coombs

doi:10.1038/nm0808-796a

Full Text - A testing approach based on tiny doses still awaits big results | PDF (139 KB) - A testing approach based on tiny doses still awaits big results

Massachusetts pours money into local life sciences research - p796

Prashant Nair

doi:10.1038/nm0808-796b

Full Text - Massachusetts pours money into local life sciences research | PDF (139 KB) - Massachusetts pours money into local life sciences research

Allergy genes flew the coop, according to evolutionary analysis - p797

Coco Ballantyne

doi:10.1038/nm0808-797a

Full Text - Allergy genes flew the coop, according to evolutionary analysis | PDF (211 KB) - Allergy genes flew the coop, according to evolutionary analysis

To know or not to know - p797

Coco Ballantyne

doi:10.1038/nm0808-797b

Full Text - To know or not to know | PDF (211 KB) - To know or not to know

News in brief - pp798 - 799

doi:10.1038/nm0808-798

Full Text - News in brief | PDF (641 KB) - News in brief

Straight talk with...Otmar Kloiber - pp800 - 801

doi:10.1038/nm0808-800

Representing some 8 million physicians from over 80 countries across the globe is no easy task, but Otmar Kloiber has handled this responsibility since 2005. As secretary general of the World Medical Association (WMA), Kloiber deals with a wide array of medical topics, ranging from drug-resistant tuberculosis to the ethics of organ transplantation. Founded shortly after World War II, the WMA is a voluntary consortium of national medical associations that fosters physician independence and promotes sound principles of medical care and ethics. Its widely recognized Declaration of Helsinki, an ethical framework designed to protect research subjects, just underwent a round of proposed edits to ensure better protection and greater rewards for research subjects. Kloiber explains the implications of these drafted changes, scheduled for final approval this fall, and the role of the WMA with Coco Ballantyne.

Abstract - | Full Text - Straight talk with...Otmar Kloiber | PDF (430 KB) - Straight talk with...Otmar Kloiber

A sporting chance - pp802 - 805

Cassandra Willyard

doi:10.1038/nm0808-802

This month, athletes from all over the world will gather in Beijing to compete for the gold. Some will win, some will lose and some will undoubtedly get injured. Cassandra Willyard explores the advances in biomedical research that might help get injured athletes back on the field faster in the future.

Abstract - | Full Text - A sporting chance | PDF (1,154 KB) - A sporting chance

Beyond GINA - p806

Paul R Billings

doi:10.1038/nm0808-806

Full Text - Beyond GINA | PDF (77 KB) - Beyond GINA

There will be fat - p807

Matthias H Tschöp reviews Rethinking Thin: The New Science of Weight Loss—and the Myths and Realities of Dieting by Gina Kolata

doi:10.1038/nm0808-807

Full Text - There will be fat | PDF (93 KB) - There will be fat

M. tuberculosis passes the litmus test - pp809 - 810

John D MacMicking

doi:10.1038/nm0808-809

One of the body's key defenders against infection—the activated macrophage—engulfs bacteria and destroys them with an acid cocktail inside lysosomes. Mycobacterium tuberculosis seems to have evolved a strategy to cope with this threat (pages 849–854).

Abstract - | Full Text - M. tuberculosis passes the litmus test | PDF (295 KB) - M. tuberculosis passes the litmus test

See also: Letter by Vandal et al.

Putting pressure on pre-eclampsia - pp810 - 812

Samir M Parikh & S Ananth Karumanchi

doi:10.1038/nm0808-810

Women with pre-eclampsia, a potentially deadly complication of pregnancy, produce agonistic autoantibodies against angiotensin receptor-1, a transmembrane protein that regulates blood pressure. Findings in mice suggest how these antibodies might help trigger the condition (pages 855–862).

Abstract - | Full Text - Putting pressure on pre-eclampsia | PDF (671 KB) - Putting pressure on pre-eclampsia

See also: Letter by Zhou et al.

Predicting the future for people with lung cancer - pp812 - 813

Yang Xie & John D Minna

doi:10.1038/nm0808-812

A large multicenter study shows that lung adenocarcinomas have messenger RNA expression signatures that greatly add to the use of clinical data in predicting an individual's survival (pages 822–827).

Abstract - | Full Text - Predicting the future for people with lung cancer | PDF (414 KB) - Predicting the future for people with lung cancer

See also: Article by Shedden et al.

Capturing cancer stem cells - p814

doi:10.1038/nm0808-814

Full Text - Capturing cancer stem cells | PDF (325 KB) - Capturing cancer stem cells

Research highlights - pp816 - 817

doi:10.1038/nm0808-816

Full Text - Research highlights | PDF (350 KB) - Research highlights

Effective induction of high-titer antibodies by viral vector vaccines - pp819 - 821

Simon J Draper, Anne C Moore, Anna L Goodman, Carole A Long, Anthony A Holder, Sarah C Gilbert, Fergal Hill & Adrian V S Hill

doi:10.1038/nm.1850

A novel immunization strategy that involves prime-boost vaccination with a recombinant adenovirus-poxvirus vector can induce strong, antigen-specific antibody responses. Antibodies induced by this viral-vector platform against a Plasmodium antigen are effective in vivo and in vitro.

Abstract - | Full Text - Effective induction of high-titer antibodies by viral vector vaccines | PDF (210 KB) - Effective induction of high-titer antibodies by viral vector vaccines | Supplementary information

Gene expression–based survival prediction in lung adenocarcinoma: a multi-site, blinded validation study - pp822 - 827

Director's Challenge Consortium for the Molecular Classification of Lung Adenocarcinoma, Kerby Shedden, Jeremy M G Taylor, Steven A Enkemann, Ming-Sound Tsao, Timothy J Yeatman, William L Gerald, Steven Eschrich, Igor Jurisica, Thomas J Giordano, David E Misek, Andrew C Chang, Chang Qi Zhu, Daniel Strumpf, Samir Hanash, Frances A Shepherd, Keyue Ding, Lesley Seymour, Katsuhiko Naoki, Nathan Pennell, Barbara Weir, Roel Verhaak, Christine Ladd-Acosta, Todd Golub, Michael Gruidl, Anupama Sharma, Janos Szoke, Maureen Zakowski, Valerie Rusch, Mark Kris, Agnes Viale, Noriko Motoi, William Travis, Barbara Conley, Venkatraman E Seshan, Matthew Meyerson, Rork Kuick, Kevin K Dobbin, Tracy Lively, James W Jacobson & David G Beer

doi:10.1038/nm.1790

Studies of gene expression in lung cancer have the potential to affect patient care, but the general applicability of the derived classifiers is unclear. David Beer and his colleagues now analyze more than 400 lung tumors from subjects at six institutions using eight different classifiers and show that the combination of molecular and clinical data best predicts patient survival (pages 812–813).

Abstract - | Full Text - Gene expression–based survival prediction in lung adenocarcinoma: a multi-site, blinded validation study | PDF (211 KB) - Gene expression–based survival prediction in lung adenocarcinoma: a multi-site, blinded validation study | Supplementary information

See also: News and Views by Xie & Minna

Hepatocyte-specific ablation of Foxa2 alters bile acid homeostasis and results in endoplasmic reticulum stress - pp828 - 836

Irina M Bochkis, Nir E Rubins, Peter White, Emma E Furth, Joshua R Friedman & Klaus H Kaestner

doi:10.1038/nm.1853

The transcription factor Foxa2, which is key for the hepatic control of glucose metabolism, is now shown in this report to also be crucial for proper bile acid homestasis in the liver, as well as to be misregulated in human cholestatic diseases.

Abstract - | Full Text - Hepatocyte-specific ablation of Foxa2 alters bile acid homeostasis and results in endoplasmic reticulum stress | PDF (583 KB) - Hepatocyte-specific ablation of Foxa2 alters bile acid homeostasis and results in endoplasmic reticulum stress | Supplementary information

Amyloid- protein dimers isolated directly from Alzheimer's brains impair synaptic plasticity and memory - pp837 - 842

Ganesh M Shankar, Shaomin Li, Tapan H Mehta, Amaya Garcia-Munoz, Nina E Shepardson, Imelda Smith, Francesca M Brett, Michael A Farrell, Michael J Rowan, Cynthia A Lemere, Ciaran M Regan, Dominic M Walsh, Bernardo L Sabatini & Dennis J Selkoe

doi:10.1038/nm1782

The synaptotoxic A protein aggregates in the brains of individuals with Alzheimer's disease. Dennis Selkoe and his colleagues identify the size of the A aggregate in the brains of individuals with Alzheimer's disease that is responsible for the deficits of learning and memory that characterize the disease.

First Paragraph - | Full Text - Amyloid- protein dimers isolated directly from Alzheimer's brains impair synaptic plasticity and memory | PDF (316 KB) - Amyloid- protein dimers isolated directly from Alzheimer's brains impair synaptic plasticity and memory | Supplementary information

Reversal of learning deficits in a Tsc2^+/- mouse model of tuberous sclerosis - pp843 - 848

Dan Ehninger, Sangyeul Han, Carrie Shilyansky, Yu Zhou, Weidong Li, David J Kwiatkowski, Vijaya Ramesh & Alcino J Silva

doi:10.1038/nm1788

Tuberous sclerosis is a neurological disorder associated with seizures and cognitive dysfunction. Alcino Silva and his colleagues find that rapamycin, an inhibitor of the mTOR signaling pathway, can ameliorate cognitive deficits in a mouse model of the disease.

First Paragraph - | Full Text - Reversal of learning deficits in a Tsc2+/- mouse model of tuberous sclerosis | PDF (234 KB) - Reversal of learning deficits in a Tsc2+/- mouse model of tuberous sclerosis | Supplementary information

A membrane protein preserves intrabacterial pH in intraphagosomal Mycobacterium tuberculosis - pp849 - 854

Omar H Vandal, Lynda M Pierini, Dirk Schnappinger, Carl F Nathan & Sabine Ehrt

doi:10.1038/nm.1795

Acidification of the phagosome is a key mechanism thought to be used by macrophages against Mycobacterium tuberculosis. The authors identify a previously undescribed gene that confers acid resistance to the bacterium and is essential for virulence (pages 809–810).

First Paragraph - | Full Text - A membrane protein preserves intrabacterial pH in intraphagosomal Mycobacterium tuberculosis | PDF (384 KB) - A membrane protein preserves intrabacterial pH in intraphagosomal Mycobacterium tuberculosis | Supplementary information

See also: News and Views by MacMicking

Angiotensin receptor agonistic autoantibodies induce pre-eclampsia in pregnant mice - pp855 - 862

Cissy C Zhou, Yujin Zhang, Roxanna A Irani, Hong Zhang, Tiejuan Mi, Edwina J Popek, M John Hicks, Susan M Ramin, Rodney E Kellems & Yang Xia

doi:10.1038/nm.1856

Direct proof that women with pre-eclampsia develop autoantibodies to the AT₁ receptor, which explains the hypertension and other symptoms of the disease, is now provided. Additionally, blocking these autoantibodies or treating with losartin, a drug that targets the AT₁ receptor, in a new mouse model of this condition helps ameliorate disease outcome (pages 810–812).

First Paragraph - | Full Text - Angiotensin receptor agonistic autoantibodies induce pre-eclampsia in pregnant mice | PDF (508 KB) - Angiotensin receptor agonistic autoantibodies induce pre-eclampsia in pregnant mice | Supplementary information

See also: News and Views by Parikh & Karumanchi

A tumor necrosis factor-–mediated pathway promoting autosomal dominant polycystic kidney disease - pp863 - 868

Xiaogang Li, Brenda S Magenheimer, Sheng Xia, Teri Johnson, Darren P Wallace, James P Calvet & Rong Li

doi:10.1038/nm1783

Polycystic kidney disease can be caused by germline mutations in the gene encoding PC2 followed by a second somatic 'hit' in the normal allele. Li and her colleagues now show that TNF- can also act as a second hit and that disease progression can be blocked by anti–TNF- treatment in an animal model.

First Paragraph - | Full Text - A tumor necrosis factor-–mediated pathway promoting autosomal dominant polycystic kidney disease | PDF (474 KB) - A tumor necrosis factor-–mediated pathway promoting autosomal dominant polycystic kidney disease | Supplementary information

Chip–NMR biosensor for detection and molecular analysis of cells - pp869 - 874

Hakho Lee, Eric Sun, Donhee Ham & Ralph Weissleder

doi:10.1038/nm.1711

A major challenge in biomedicine is the rapid and accurate measurement of biomarkers in biological samples. Here, Lee et al. describe a chip-based NMR diagnostic platform that can perform sensitive and selective measurements on small volumes of unprocessed biological samples. This miniaturized biosensing system is high throughput, low cost and portable, and its utility is shown in a number of biomedical applications.

Abstract - | Full Text - Chip–NMR biosensor for detection and molecular analysis of cells | PDF (346 KB) - Chip–NMR biosensor for detection and molecular analysis of cells | Supplementary information

Mouse embryonic stem cell–based functional assay to evaluate mutations in BRCA2 - pp875 - 881

Sergey G Kuznetsov, Pentao Liu & Shyam K Sharan

doi:10.1038/nm.1719

Kuznetsov and his colleagues address a pressing problem in risk assessment for predisposition to breast cancer—whether a particular allele is cancer predisposing or not. Using a two-tiered approach, they have developed a functional assay for the classification of BRCA2 sequence variants of unknown importance. The assay may serve as a model to generate functional assays for other human disease genes.

Abstract - | Full Text - Mouse embryonic stem cell–based functional assay to evaluate mutations in BRCA2 | PDF (478 KB) - Mouse embryonic stem cell–based functional assay to evaluate mutations in BRCA2 | Supplementary information

Adenovirus-mediated gene expression imaging to directly detect sentinel lymph node metastasis of prostate cancer - pp882 - 888

Jeremy B Burton, Mai Johnson, Makoto Sato, Sok Boon S Koh, David J Mulholland, David Stout, Arion F Chatziioannou, Michael E Phelps, Hong Wu & Lily Wu

doi:10.1038/nm.1727

The degree of lymph-node metastasis in prostate cancer is crucial for both staging the disease and planning treatment. Here, Burton and colleagues describe a one-step, non-invasive imaging technology using prostate-specific adenoviral vectors that express imaging reporter genes. This set-up specifically and accurately detects lymph-node metastases in a model of human prostate cancer and eliminates the need for invasive lymphadenectomy required by the current lymphoscintigraphy method.

Abstract - | Full Text - Adenovirus-mediated gene expression imaging to directly detect sentinel lymph node metastasis of prostate cancer | PDF (687 KB) - Adenovirus-mediated gene expression imaging to directly detect sentinel lymph node metastasis of prostate cancer | Supplementary information

Corrigendum: Genomic signatures to guide the use of chemotherapeutics - p889

Anil Potti, Holly K Dressman, Andrea Bild, Richard F Riedel, Gina Chan, Robyn Sayer, Janiel Cragun, Hope Cottrill, Michael J Kelley, Rebecca Petersen, David Harpole, Jeffrey Marks, Andrew Berchuck, Geoffrey S Ginsburg, Phillip Febbo, Johnathan Lancaster & Joseph R Nevins

doi:10.1038/nm0808-889

Full Text - Corrigendum: Genomic signatures to guide the use of chemotherapeutics | PDF (141 KB) - Corrigendum: Genomic signatures to guide the use of chemotherapeutics