Volume 17 Issue 2, February 2011

In December, Jeremy Berg announced plans to step down from the helm of the US National Institute of General and Medical Sciences (NIGMS), the $2 billion branch of the National Institutes of Health charged with funding basic research related to diverse biological processes and diseases. Ahead of his departure, Michelle Pflumm spoke to Berg about his contributions at NIGMS and his plans moving forward.

The US system of classifying national security information is bloated and dysfunctional, shielding the government from the scrutiny it needs to avoid error and abusive practices. In the medical field, this secrecy has, in rare cases, enabled unethical, state-sponsored research to proceed without public knowledge. The Fundamental Classification Guidance Review that is now underway could make a difference—if it's done right.

Triglyceride-rich lipoproteins (TRLs) transport lipid calories to tissues that need energy, but TRLs can also contribute to obesity and vascular disease. A newly discovered pathway shows how cold exposure increases the uptake and combustion of TRLs by brown adipose tissue, thereby correcting harmful hyperlipidemias (pages 200–205).

New tuberculosis vaccines are urgently needed to reduce the threat of this devastating disease. An approach consisting of a fusion protein of three tuberculosis antigens provides significant protection in before- and after-exposure challenge mouse models, representing a crucial step forward in tackling tuberculosis in latently infected individuals (pages 189–194).

Hyperglycemia is a risk factor for poor outcomes after intracerebral hemorrhage (ICH), but what drives its effects on ICH is unknown. A new study shows that plasma kallikrein mediates hyperglycemia-induced hematoma expansion in rats and mice with ICH by inhibiting blood platelets (pages 206–210).

A microRNA decreases the expression of the adhesion molecule CD44 in prostate cancer stem cells (CSCs), blocking tumor growth and metastasis in mice (pages 211–215). Systemic delivery of this negative regulator may open new avenues for targeting CSCs to halt cancer.

Chronic inflammation is associated with obesity, but the pathways that mediate this phenomenon are not fully characterized. The nucleotide-binding domain, leucine-rich–containing family, pyrin domain–containing-3 (Nlrp3) inflammasome functions as a sensor to detect danger signals and induce downstream inflammatory signaling that contributes to obesity-associated conditions such as insulin resistance (pages 179–188).

Infection with methicillin-resistant Staphylococcus aureus (MRSA) can cause symptoms ranging from mild skin infections to more severe disease in various organs, even among healthy individuals. The ability of this pathogen to escape our immune arsenal and overcome antibiotic therapy poses a challenge to preventing their spread and treating the related symptoms. In 'Bench to Bedside', Scott Kobayashi and Frank DeLeo explore new approaches for vaccine development that focus on antigens required for establishment of disease. Studies with infected mice immunized against S. aureus coagulases—important for abscess formation and bloodstream infection—suggest such an approach may be used to reduce bacterial load and protect against severe disease in humans. In 'Bedside to Bench', Michael Otto examines a large human study where the presence of genes encoding Panton-Valentine leukocidin toxin (PVL) in community-associated MRSA did not correlate with complicated skin structure infections—a result opposing the widespread notion that PVL is the primary CA-MRSA virulence factor.

Definitive diagnosis of prion disease currently requires postmortem brain tissue. Now, Ryuichiro Atarashi and colleagues have discovered an assay that can identify prions in human cerebrospinal fluid. This assay could allow for diagnosis of disease in living humans.

Obesity is generally considered an inflammatory state. Vishwa Dixit and his colleagues have now shown that excess dietary lipids leads to the activation of the Nlrp3 inflammasome, a sensor of the innate immune system, and that its genetic deficiency results in decreased inflammation and improved insulin sensitivity. These results suggest a possible new therapeutic avenue to treat the effects of obesity.

There is an essential need for vaccines that can prevent primary infection by Mycobacterium tuberculosis and control its reactivation in individuals with latent disease. Claus Aagaard et al. now report the development of a dual-function vaccine that shows protective efficacy in mice by both inhibiting infection upon initial pathogen exposure and by impairing reactivation of latent infection with M. tuberculosis.

Pandemic influenza viruses often cause severe disease in middle-aged adults without preexisting comorbidities. A serum antibody preexisting in middle-aged adults cross-reacts with, but does not protect against, 2009 H1N1 influenza virus. The existence of this antibody may account for the unusual age distribution of severe flu cases during pandemics.

Elevated triglyceride levels often occur in obesity and can contribute to cardiovascular disease. Brown adipose tissue (BAT) is known to burn fat, and now Joerg Heeren and his colleagues show that BAT actively takes up triglycerides in cold conditions, suggesting a possible therapy to lower triglyceride levels in states of obesity.

Intracerebral hemorrhage, a common cause of stroke, has more dire consequences in diabetics than in nondiabetics. Using experimental rodent models, Jia Liu et al. find that the deleterious effects of diabetes on intracerebral hemorrhage may be due to the action of the protein plasma kallikrein, discovered to directly inhibit platelet aggregation through an osmolarity-sensitive mechanism.

The authors show that miR-34a regulates progenitor and metastatic properties of prostate cancer cells, and they identify CD44 as a relevant target of the microRNA. The inhibition of metastasis observed after systemic delivery of miR-34a suggests that it could be used as a potential therapeutic agent in prostate cancer.

The current diagnosis of acute kidney injury involves the measurement of renal biomarkers, such as serum creatinine, which provide a crude means of detecting cellular stress and injury. To determine whether Ngal expression provides an alternate renal biomarker capable of detecting the initial phases of renal injury, Paragas et al. have developed an Ngal reporter mouse that offers a noninvasive and real-time method for the continuous and quantitative reporting of cell stress and injury at the injury site.

Tony Ko and his colleagues introduce a fluorescence microendoscopy imaging approach for time-lapse studies of deep brain tissue previously inaccessible to conventional optical imaging techniques. It can be used to study the cellular effects of brain disease over weeks to months with comparable resolution to light microscopy. They use the approach to monitor individual hippocampal neurons, neuronal dendrites and blood vessels and to follow the process of glioma angiogenesis.