Street connectivity and urban sprawl
Street design patterns: Dead ends denoted by red circles and highly connected intersections by blue squares.
Because the layouts of roads tend to establish urban development patterns for decades, the growth of residential roads can provide insight into patterns of urban sprawl. Christopher Barrington-Leigh and Adam Millard-Ball (pp. 8244–8249) constructed a high-resolution time series of street network connectivity between 1920 and 2012, quantifying the number of connected roads at intersections, or nodal degree of intersections, which may be used as a metric of urban sprawl. Gridded layouts display high connectivity and low sprawl, and abundant dead ends display low connectivity and high sprawl. The authors report that urban sprawl increased steadily until the mid-1990s, when construction of new streets became more grid-like and connected than before, leading to a peak in US street network sprawl around 1994. The mean nodal degree of intersections increased, indicating a decrease in sprawl by around 9% between 1994 and 2012, with the largest increases in the counties that contain Austin, TX; Charlotte, NC; and Gainesville, FL. However, the authors found that areas built with low-connectivity street networks remained as such, even as the street network expanded. Government policies to promote gridded streets may reduce sprawl, according to the authors. — P.G.
Greenhouse gas emissions and environmentalism
New York City’s daily CO2 emissions, visualized as 1-ton spheres. Image courtesy of Flickr/Carbon Visuals.
Previous studies suggest that population and economic affluence are among the main drivers of anthropogenic climate change. Thomas Dietz et al. (pp. 8254–8259) examined whether political factors could counteract the effects of population and affluence on greenhouse gas emissions. The authors compared greenhouse gas emissions between all 50 US states and within each state over time going back to 1990, and determined how emissions correlated with population, gross state product per capita, employment rate, and environmentalism. Environmentalism was measured by the environmental voting record of a state’s congressional delegation as rated by the League of Conservation Voters. The authors found a strong negative correlation between a state’s greenhouse gas emissions and its level of environmentalism in 1990. A state’s emissions tended to increase over time independent of other factors, but a 1% increase in environmentalism tended to reduce emissions by an amount more than sufficient to compensate for this annual increase. Between states, the reduction in emissions associated with strong environmentalism was more than half the increase in emissions associated with high population. The results suggest that at the state level environmentalism may help moderate the effects of population and economic growth on greenhouse gas emissions, according to the authors. — B.D.
Anti-HIV immune response and infection risk
HIV-infected T cell. Image courtesy of NIH.
Immune responses against HIV-1 have been documented in uninfected people exposed to the virus, but the association between such responses and subsequent infection risk remains unclear. Peter Kuebler et al. (pp. 8379–8384) compared immune responses mounted against an array of HIV-1 antigens by two sets of peripheral blood mononuclear cell samples: 84 samples collected prior to infection from men who became seropositive after enrollment in a 2007 trial of preexposure prophylaxis (PrEP) with the HIV drug Truvada and 480 samples from men who remained seronegative throughout the trial, including those who received the drug or placebo. T-cell responses, indicated by levels of the cytokine IFN-γ, against the pathogenesis-related HIV-1 antigens Gag, Nef, Integrase, and Vif were significantly higher among those who remained seronegative, compared with those who seroconverted. Further, each 10-fold rise in Vif- and Integrase-specific T-cell responses was associated with a reduction in infection risk of 64% and 48%, respectively. The IFN-γ–secreting cells were found to be largely of the CD4+ or CD8+ effector memory type of T cells. A prospective study is required to establish correlates of anti–HIV-1 protective immunity, but uncovering antigen-specific, risk-related immune responses in uninfected people from PrEP trial data might aid efforts to design preventive vaccines, according to the authors. — P.N.
Proteolysis and Alzheimer’s disease
Cleavage of amyloid precursor protein (blue) by enzymes to form amyloid-β (yellow).
The cleavage of amyloid precursor protein (APP) to form amyloid-β (Aβ) is thought to constitute a key step in the development of Alzheimer’s disease (AD). The α-secretase a disintegrin and metalloproteinase 10 (ADAM10) cleaves APP in such a way as to preclude Aβ formation, and may therefore affect the development of AD, but little is known about the regulation of ADAM10. Grant Corbett et al. (pp. 8445–8450) found that peroxisome proliferator-activated receptor α (PPARα), a transcription factor that regulates genes involved in fatty acid metabolism, affects the expression of ADAM10 and consequently the formation of Aβ. Neurons from mice lacking PPARα showed reduced expression of ADAM10, compared with neurons from wild-type mice. Introducing PPARα into deficient neurons using a virus restored ADAM10 expression. Both gemfibrozil, a drug that stimulates PPARα, and retinoic acid, a derivative of vitamin A, helped recruit PPARα to the Adam10 gene promoter, and increased cleavage of APP by ADAM10. Mice lacking PPARα produced a greater amount of Aβ than wild-type mice, and in a mouse model of AD, the PPARα-deficient mice had a greater amount of Aβ plaques in their brains and shorter life expectancies than mice with PPARα. The results suggest a previously unknown role for PPARα in AD that might render the protein a potential therapeutic target. — B.D.
Targeting cytomegalovirus-infected cells
Human cytomegalovirus (HCMV) is an opportunistic pathogen that can be life-threatening in immunocompromised individuals. Drugs used to treat HCMV infection are associated with adverse side effects and the development of drug-resistant virus. Katja Spiess et al. (pp. 8427–8432) engineered a fusion toxin protein (FTP) to selectively target and kill HCMV-infected cells by linking the receptor-binding domain of the chemokine CX3CL1 to the cytotoxic domain of Pseudomonas aeruginosa Exotoxin A (PE), which is lethal to cells. CX3CL1 selectively binds to two receptors: HCMV-encoded US28, which is expressed only by HCMV-infected cells, and an endogenous receptor, CX3CR1. The CX3CL1-PE FTP bound to US28 with 80-fold higher affinity than to CX3CR1 and preferentially killed virus-infected cells, including cells infected with ganciclovir-resistant virus. To further enhance the specificity of the FTP for virus-infected cells, the authors designed 35 CX3CL1 variants with mutations in the chemokine domain. An FTP containing one such variant, F49A-FTP, demonstrated ∼103-fold higher potency against US28-expressing cells than against cells expressing CX3CR1. F49A-FTP displayed higher potency than ganciclovir against HCMV-infected cells and superior clearance of the virus from HCMV-infected mice. Rational design of FTPs targeting virally encoded receptors may prove useful against a number of pathogenic viruses, according to the authors. — C.B.
Perceptual dynamics in binocular rivalry
Participants saw a moving musical score that was congruent or incongruent with music being played.
When the images perceived by left and right eyes do not match and cannot be resolved into a single image, the images can compete with each other, fluctuating between perceptual dominance and suppression, although additional sensory inputs can influence perception dynamics. To investigate the effect of music on binocular rivalry, Minyoung Lee et al. (pp. 8493–8498) monitored the suppression and dominance durations of a moving musical score, perceived with the left eyes of 64 people, while their right eyes saw a simple moving grating. The authors also presented audio in some trials that either matched or did not match the musical notes seen by participants. The authors found that congruence between what participants saw and heard lengthened the dominance duration of the musical score, but only in participants who were able to read music. Further, the authors found that auditory congruence or incongruence had little effect on the suppression duration of the musical score, regardless of musical training. Neither differential eye movement nor differing response times to congruent and incongruent presentations could account for the increased dominance duration. The results suggest that abstract and semantic information contained in musical notes may not be inferentially processed while suppressed, according to the authors. — P.G.