Transdermal detection of malaria
A potential field-based diagnostic malaria detection method, targeted at vapor nanobubbles produced by hemozoin nanoparticles.
Currently, detecting malaria infection in a patient requires blood sampling and a set of reagents, rendering detection a time- and resource-intensive process. Rapid, noninvasive detection of malaria could aid global malaria eradication efforts. To develop a transdermal diagnostic method, Ekaterina Lukianova-Hleb et al. (pp. 900–905) harnessed the optical properties of hemozoin, a nanoparticle produced in blood by the malaria parasite. The authors found that hemozoin absorbs the energy from a short laser pulse and vaporizes a small volume of liquid around itself to create a vapor nanobubble detectable both optically and acoustically. The authors tested the diagnostic method in hemozoin crystals suspended in water, in malaria-infected human red blood cells, and in malaria-infected mice. In the malaria-infected mouse, the authors transdermally monitored vapor nanobubbles with a photoacoustic probe positioned over a shallow blood vessel in the mouse’s ear. Hemozoin-generated vapor nanobubbles were detectable in all studied systems, the authors report, at levels as low as 0.0001% infected red blood cells. According to the authors, the method does not appear to cause damage to tissues or uninfected blood cells and may be useful for rapid, field-based detection or screening of malaria. — P.G.
Improving the robustness of synthetic gene circuits
Synthetic gene circuits have allowed researchers to create customized cellular phenotypes from a collection of genetic parts that regulate protein production. But the circuits are limited by their abilities to withstand changes in the intra- and extracellular environments. Faiza Hussain et al. (pp. 972–977) report that the environmental sensitivity can be reduced by simultaneously engineering circuits at both the protein and network levels. The authors constructed a synthetic genetic clock that keeps time independently of temperature: an important trait, as high temperatures accelerate biochemical reactions. Upon examining a previously described gene circuit constructed in Escherichia coli—a synthetic dual-feedback oscillator with a temperature-dependent period—the authors hypothesized that a single amino acid mutation to the circuit’s core transcriptional repressor that prevents the repressor from binding its target promoter at high temperatures would allow the oscillator to compensate for fluctuations in temperature. The authors used this previously identified mutant to craft a synthetic gene oscillator that could maintain a constant period of 48 min at temperatures ranging from 30 to 41 °Celsius. Without the mutation, the authors report, the period of the oscillator dropped from 60 min to 30 min over the same temperature range. According to the authors, the study demonstrates that protein-level modifications can increase the robustness of synthetic gene circuits in the face of changing environmental conditions. — A.G.
Cell-mediated immunity to the H7N9 influenza virus may vary by ethnicity
Humans have no prior history with the H7N9 influenza virus that emerged unexpectedly in February 2013 and thus lack protective antibodies against the virus. Animal and human studies suggest that, in the absence of protective antibodies against a new influenza strain, cross-reactive CD8+ T lymphocytes (CTLs) generated previously against other influenza strains can diminish disease severity, and may therefore provide some protection against the H7N9 virus. Sergio Quiñones-Parra et al. (pp. 1049–1054) investigated the capacity of preexisting influenza–specific CTLs to respond to the H7N9 virus in individuals not previously exposed to the virus. The authors found that 28% of the H7N9 peptides with the capacity to elicit CTL responses are also found in other influenza A viruses that caused past human pandemics or epidemics. The authors then estimated that the human leukocyte antigens (HLAs) capable of presenting immunogenic influenza peptides to CTLs are present in approximately 16–57% of the population, and vary in prevalence depending on ethnicity. Analyses of blood cells from 52 healthy human donors incubated with the peptides in vitro revealed that some HLA alleles elicit robust CTL responses against any human influenza A virus, including H7N9, whereas other alleles, such as those that tend to be prevalent in the indigenous people of Alaska and Australia, displayed limited CTL responses. The findings suggest that there may be ethnic differences in the ability to mount a CTL-based immune response to the H7N9 virus, according to the authors. — N.Z.
Stimulating environments help keep the brain young
Mice in an enriched environment run and explore a maze.
Exposure to environments rich in physical, social, and cognitive stimulation is known to boost brain function. Environmental enrichment enhances the ability of neural pathways to change in response to experiences, even in adult animals, whose brains are typically less plastic or adaptable than those of juveniles. Franziska Greifzu et al. (pp. 1150–1155) found that environmental enrichment preserves and restores juvenile-like plasticity in the adult mouse brain and protects adult mice from stroke-induced impairments in plasticity. The authors raised mice in cages with running wheels, a variety of mazes, and plenty of opportunities for social interactions. To measure plasticity, the authors deprived the adult animals of visual input to one eye and recorded the resulting changes in neural activity in the primary visual cortex (V1)—a brain region that processes visual information. The authors report that mice raised in the enriched environment showed strong plasticity in V1, even in late adulthood, and were protected from impairments in V1 plasticity following a stroke induced during adulthood. Environmental enrichment also restored V1 plasticity in adult mice that were first raised in a standard cage until the age at which V1 plasticity typically disappears. The authors suggest that environmental enrichment could represent a nonpharma-cological tool for preserving and restoring neural plasticity in the adult brain. — J.W.
Brain changes tied to electroconvulsive therapy
ECT-induced gray matter increase (red) and decrease (blue).
The precise mechanism by which electroconvulsive therapy (ECT) alleviates symptoms of mood disorders in some patients has long remained unclear. Juergen Dukart et al. (pp. 1156–1161) attempted to uncover changes in brain anatomy and clinical symptoms associated with ECT in a preliminary study of 56 individuals. Of the study participants, 24 patients were diagnosed with unipolar or bipolar disorder and responsive to drug treatment; 10 patients, similarly diagnosed, were unresponsive to drug treatment and hence administered ECT on the right side of the head at two 3-month intervals after recruitment; and 21 healthy volunteers served as a comparison group. Before and after ECT administration, the authors used structural MRI to monitor regional changes in gray matter volume in brain areas implicated in the disorders and a clinical depression rating scale to assess disease symptoms. The authors report that right unilateral ECT was associated with local changes in certain areas of the brain’s right hemisphere, in particular an increase in gray matter volume in the hippocampal complex and Brodmann area 25. Further statistical analysis suggested a link between ECT-associated brain changes and the severity of depressive symptoms, hinting at the plausibility of a treatment effect potentially mediated by structural changes. Because of the study’s small size, differences in the patients’ depression severity and treatment histories, and other potential confounders, the findings must be verified in a larger cohort with focused brain stimulation techniques, but the results provide insight into the potential effects of ECT on the brain, according to the authors. — P.N.