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

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

Published online: 20 July 2008; | 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.

Abstract - | Full Text - Gene expression–based survival prediction in lung adenocarcinoma: a multi-site, blinded validation study | PDF (214 KB) - Gene expression–based survival prediction in lung adenocarcinoma: a multi-site, blinded validation study | Supplementary information

A membrane protein preserves intrabacterial pH in intraphagosomal Mycobacterium tuberculosis

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

Published online: 20 July 2008; | 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.

First Paragraph - | Full Text - A membrane protein preserves intrabacterial pH in intraphagosomal Mycobacterium tuberculosis | PDF (387 KB) - A membrane protein preserves intrabacterial pH in intraphagosomal Mycobacterium tuberculosis | Supplementary information

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

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

Published online: 22 June 2008; | 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 (237 KB) - Reversal of learning deficits in a Tsc2+/- mouse model of tuberous sclerosis | Supplementary information

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

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

Published online: 22 June 2008; | 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 (319 KB) - Amyloid- protein dimers isolated directly from Alzheimer's brains impair synaptic plasticity and memory | Supplementary information

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

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

Published online: 15 June 2008; | 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 (479 KB) - A tumor necrosis factor-–mediated pathway promoting autosomal dominant polycystic kidney disease | Supplementary information

Blocking TGF-–Smad2/3 innate immune signaling mitigates Alzheimer-like pathology

Terrence Town, Yasmina Laouar, Christopher Pittenger, Takashi Mori, Christine A Szekely, Jun Tan, Ronald S Duman & Richard A Flavell

Published online: 30 May 2008; | doi:10.1038/nm1781

First Paragraph - | Full Text - Blocking TGF-–Smad2/3 innate immune signaling mitigates Alzheimer-like pathology | PDF (545 KB) - Blocking TGF-–Smad2/3 innate immune signaling mitigates Alzheimer-like pathology | Supplementary information

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

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

Published online: 11 July 2008; | 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 (689 KB) - Adenovirus-mediated gene expression imaging to directly detect sentinel lymph node metastasis of prostate cancer | Supplementary information

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

Sergey G Kuznetsov, Pentao Liu & Shyam K Sharan

Published online: 06 July 2008; | 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 genes associated with human diseases.

Abstract - | Full Text - Mouse embryonic stem cell–based functional assay to evaluate mutations in BRCA2 | PDF (484 KB) - Mouse embryonic stem cell–based functional assay to evaluate mutations in BRCA2 | Supplementary information

Chip–NMR biosensor for detection and molecular analysis of cells

Hakho Lee, Eric Sun, Donhee Ham & Ralph Weissleder

Published online: 06 July 2008; | 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 (348 KB) - Chip–NMR biosensor for detection and molecular analysis of cells | Supplementary information