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Neutrophil extracellular traps (NETs) are a newly identified mechanism by which neutrophils capture and kill pathogens. In this issue, Marcos et al. identify CXCR2 as a neutrophil receptor that can trigger NET formation and show that NETs may exacerbate chronic inflammation in cystic fibrosis. The cover image depicts Shigella caught in a NET released by a nearby neutrophil. (Credit: Science Photo Library)
Singapore's current investment in science is remarkably strong, but it isn't yet clear if the resulting knowledge and innovation will go on to fuel economic growth, as the country expects.
Rajiv Shah was less than a month into his position at the helm of the US Agency for International Development (USAID) when the catastrophic earthquake that hit Haiti propelled him to the frontline of an international relief effort. Elie Dolgin spoke to Shah about how he plans to make progress toward reaching the targets.
The murder of ten aid workers, including an optometrist and a surgeon, in Afghanistan last month refocused the world's attention on the difficulties of providing health care in conflict zones. Beyond the dangers of delivering acute care such as surgery, dispensing medicines for chronic illnesses ranging from HIV to diabetes remains a challenge in areas affected by war. Cassandra Willyard looks at the lessons relief agencies have learned in recent years providing care amidst increasingly complex conflicts.
Despite continued doubts about the clinical utility of direct-to-consumer genetic tests, tens of thousands of people have sent away tubes full of their saliva to learn more about their genetic profiles. Armed with such DNA data, a number of early adopters are showing how empowering—and beneficial to science—personal genetic information can be. Elie Dolgin reports on one company's plans to make medical genetics more participatory.
The US legal system has rightly constructed a high barrier to prosecuting individual corporate employees. However, when a person deliberately masterminds massive pharmaceutical fraud, he or she needs to be held accountable. Whistleblowers hold the key to building stronger, more viable cases against those who devise large-scale corporate criminal activity.
Recent studies show that Musashi-2 (MSI2), a molecule that binds RNA, increases proliferation of normal and malignant blood stem cells. In humans, increased amounts of MSI2 correlate with poor prognosis of leukemia—indicating that MSI2 may be a target to treat this type of cancer.
Thyroid hormones increase the energy metabolism of the body in a process called 'thyroid thermogenesis'. Its molecular mechanism, however, has been elusive. Recent findings in rats suggest that it is localized to brown adipose tissue—our one truly thermogenic organ—and is mediated via the brain (pages 1001–1008).
Thick, adherent mucus in the airway causes respiratory failure—the leading cause of death in cystic fibrosis. A new study now shows how the formation of neutrophil extracellular traps (NETs) in the airway, in an attempt to kill colonizing bacteria, results in chronic cell carnage that thickens the sputum, worsening lung function in individuals with cystic fibrosis (pages 1018–1023).
A drug that discourages alcohol ingestion has shown promise as a treatment for cocaine addiction. New findings in rats suggest a potential mechanism—the drug decreases amounts of dopamine in the brain (pages 1024–1028). Blocking enzymes that regulate dopamine abundance may be a new way to treat cocaine addiction and prevent relapse in humans.
The complexity of human metastatic cancer is difficult to mimic in mouse models. As a consequence, seemingly successful studies in murine models do not translate into success in late phases of clinical trials, pouring money, time and people's hope down the drain. In 'Bedside to Bench', Isaiah Fidler and Lee Ellis discuss crucial parameters in cancer growth and therapy and emphasize the disparity between studies in humans and mice. In 'Bench to Bedside', Terry Van Dyke shows how pancreatic tumors developed de novo in the organ site in mice can explain therapy failure in people with cancer and serve as a model to test new drugs.
Ebola and Marburg viruses cause lethal hemorrhagic fevers for which there are presently no licensed preventive or curative antiviral agents. In a new report, Warren et al. show that positively charged phosphorodiamidate morpholino oligomers administered shortly after viral infection can protect nonhuman primates from this frequently fatal disease.
The rapid mutation rate of HIV-1 enables its escape from neutralizing antibodies (NAbs) in infected individuals. Bunnik et al. now show that the immune pressure exerted by NAbs has, over the course of the HIV epidemic, altered the HIV-1 envelope glycoprotein such that HIV-1 variants isolated from recently infected individuals are more resistant to NAbs, compared with viral variants isolated from individuals infected at the start of the epidemic. Their results suggest the need to carefully select the envelope gene used in today's vaccine efforts.
Mutations in the kinase LRRK2 have been linked to Parkinson's disease. Now, Ted Dawson and his colleagues have identified inhibitors of LRRK2 that can reduce LRRK2-induced neurotoxicity in cell culture and in mice.
Thyroid hormones are well known to regulate whole-body energy metabolism, which was believed to occur as a direct effect on individual cells in the periphery. But Antonio Vidal-Puig and his colleagues now show that these thyroid hormone effects on energy regulation are actually indirect, as they regulate AMPK activity in the hypothalamus and thus central signaling to brown adipose tissue in the periphery.
Pathologically altered stromas are a common contributing factor to cancer progression and fibrogenesis. This report uncovers the role of LOXL2 in the creation and maintenance of the pathological microenvironment of human cancers and fibrotic diseases and presents the development of a LOXL2-specific antibody that shows therapeutic activity in tumor as well as lung and liver fibrosis models.
Recent studies have shown that neutrophil extracellular traps (NETs) can capture and kill bacteria but may also contribute to chronic inflammation. The mechanisms that trigger NET formation are not yet fully elucidated. Marcos et al. now report that stimulation of the chemokine receptor CXCR, induces NET formation and that NETs are present in airway fluids of individuals with cystic fibrosis. Blocking CXCR2 activation in the lung reduced NET formation and improved lung function in a mouse model of cystic fibrosis.
ALDH-2 inhibitors are a potential treatment for alcohol addiction. Now, Lina Yao et al. show that ALDH-2 inhibitors can reduce addiction to cocaine in rats by generating a dopamine metabolite called THP. THP inhibits an enzyme involved in dopamine synthesis, thereby blocking dopamine production in response to cocaine.
Our knowledge of the diversity of human T cell receptors (TCRs) is limited by tolerance mechanisms—most high-avidity autoreactive T cells are deleted. Li et al. have now transferred the entire TCR-αβ gene loci into mice, which will facilitate the study of T cell responses to human antigens.
One of the main shortcomings of cell therapy is the poor persistence and loss of functionality of donor cells after transfer. Using adjuvant drug–loaded nanoparticles conjugated directly to the surface of therapeutic donor cells, an approach designed to minimize the systemic side effects of adjuvant drugs, Matthias Stephan and his colleagues show enhanced functionality in a model of adoptive T cell therapy for cancer and of hematopoietic stem cell engraftment.
Standard methods of neutrophil isolation require skilled personnel, are time consuming and use large blood volumes. Kotz and his colleagues have developed a rapid microfluidic chip-based approach for rapidly isolating neutrophils directly from whole blood with 'on-chip' processing for mRNA and protein isolation. The device, which yields sufficient quantities and purities for downstream genomic or proteomic analysis, was validated in a multicenter clinical study of the immune response to severe trauma and burn injury.