Volume 14 Issue 8, August 2008

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.

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.

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).

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).

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).

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.

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).

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.

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

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.

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).

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).

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-α can also act as a second hit and that disease progression can be blocked by anti–TNF-α treatment in an animal model.

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.

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.

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.