In This Issue

doi:10.1073/iti1616113

New Research In

Ebola virus transmission and intervention effectiveness

Ebola treatment center in Kerry Town, Sierra Leone. Image courtesy of PO (Phot) Carl Osmond (Ministry of Defence, United Kingdom).

Concern over the reemergence of Ebola virus disease (EVD) has prompted studies of past outbreaks that are aimed at an improved understanding of EVD transmission and the effectiveness of intervention strategies. Li-Qun Fang et al. (pp. 4488–4493) used data from the recent EVD outbreak in Sierra Leone from May 2014 to September 2015 to map the spatial and temporal distribution of cases on multiple levels. The authors estimated that the transmissibility, defined as the average number of secondary infections per patient per week, decreased by 43% after the strategic plan of the United Nations Mission for Emergency Ebola Response (UNMEER) was initiated in October 2014, and by 65% relative to the pre-October 2014 level once 100% case isolation and safe burials were achieved in December 2014. EVD transmission was associated with high population density, proximity to Ebola treatment centers, high cropland coverage, and temperatures higher or lower than 27 °C. The authors also found that the probability of a patient infecting a household member decreased by an estimated 82%, from 9.3% to 1.7% following the UNMEER campaign. The results might help develop effective intervention strategies for future outbreaks, according to the authors. — B.D.

Why anxiety peaks in adolescence

Anxiety disorders peak in incidence during adolescence, but many treatments are based on studies in adults. Understanding how genetic factors influence the risk of developing psychiatric disorders at different stages of brain development is critical for optimizing treatments. To address this question, Dylan Gee et al. (pp. 4500–4505) studied how a common genetic variant that affects endocannabinoid signaling alters the development of frontolimbic circuitry, possibly contributing to the emergence of anxiety-related behavior during adolescence. The authors used diffusion MRI to measure the connectivity between prefrontal cortex and limbic structures in 1,050 individuals 3–21 years of age. Some participants had higher levels of endocannabinoids due to a genetic variant that interferes with the activity of the fatty acid amide hydrolase (FAAH) enzyme, which breaks down endocannabinoids. Compared with individuals without the FAAH variant allele, those with the allele displayed higher frontolimbic connectivity and lower self-reported anxiety, but only after 12 years of age. The findings demonstrate that the effect of this genetic factor on brain circuitry and anxiety-related behavior emerges during adolescence. According to the authors, the results might aid the development of biomarkers for anxiety, as well as precision medicine approaches that optimize the treatment of adolescents with psychiatric disorders. — J.W.

Mussel-inspired wet adhesives

The MFP-3s peptide’s flat conformation on hydrophobic surfaces increases adhesion.

Recent decades have witnessed a growing demand for biologically inspired, water-resistant adhesives for applications such as dental and medical transplants and coronary artery coatings. Research in this area has focused on mussels, which form strong, water-resistant bonds to various underwater surfaces. To advance the development of next-generation wet adhesives, Zachary Levine et al. (pp. 4332–4337) combined an experimental approach with theoretical modeling to examine the molecular basis of the gluelike properties of mussel foot proteins. The authors mounted two opposing surfaces in a custom-designed instrument and filled the thin gap between the two surfaces with a solution containing a synthetic peptide derived from mussel foot proteins, namely the MFP-3s peptide. During the approach and separation of the surfaces from one another, the instrument measured the interaction forces between the surfaces as a function of distance, at the nanometer length scale. The MFP-3s peptides exhibited strong adhesion forces between hydrophobic surfaces, but weak adhesion forces between hydrophilic surfaces. Simulations revealed the molecular origin of this difference in adhesion. According to the authors, analysis of the molecular interactions that enhance the stickiness of mussel foot proteins could lay the foundation for the development of water-resistant glues for a range of biomedical applications. — J.W.

Imaging epigenetic states in mammalian genomes

Procedure for labeling and simultaneously imaging 5mC and 5hmC.

Epigenetic modifications are chemical processes that affect gene activity without altering the DNA sequence. In mammalian genomes, two major epigenetic modifications called 5-methylcytosine (5mC) and 5-hydroxymethylcytosine (5hmC) play important roles in embryonic development and diseases such as cancer, but little is known about the interplay between these modifications due to a lack of suitable techniques for simultaneously revealing the locations of nearby 5mC and 5hmC sites. Chun-Xiao Song et al. (pp. 4338–4343) developed an ultrasensitive single-molecule imaging technique to detect and quantify 5mC and 5hmC in the same DNA molecule. Using trace amounts of synthetic DNA and genomic DNA from different mouse tissues, the authors labeled 5mC and 5hmC with red and green fluorescent dyes, respectively, and imaged the molecules using a fluorescence microscope. Next, the authors used a biophysical technique called single-molecule fluorescence resonance energy transfer to measure the distance between the labeled 5mC and 5hmC molecules. The findings revealed high levels of adjacent and opposing 5mC and 5hmC molecules at CpG sites—DNA regions consisting of a cytosine nucleotide followed by a guanine nucleotide. According to the authors, these widespread methylated and hydroxymethylated CpG sites represent an important epigenetic state in the mammalian genome and could play previously unappreciated roles in gene regulation. — J.W.

Preexisting immunity against influenza viruses

Memory T cells derived from conserved viral proteins provide protection against specific influenza A viruses, but the emergence of mutant strains can reduce immune efficacy. Sophie Valkenburg et al. (pp. 4440–4445) found that T-cell receptors (TCRs) specific to a prominent human memory T-cell epitope are capable of recognizing multiple variants of influenza A viruses. The authors compared TCRs targeted to this highly immunogenic epitope, which is broadly conserved across both seasonal and pandemic influenza A viruses, as well as TCRs targeted to another prominent, highly variable epitope, with more than 20 naturally occurring sequences. The authors found that the type of TCRs elicited by the conserved epitope cross-reacted with a wider spectrum of variant influenza A viruses than TCRs elicited by the hypervariable epitope. Structural analysis revealed that the TCRs specific to the conserved epitope can cross-recognize naturally occurring peptide variants via a phenomenon called induced-fit molecular mimicry. The results suggest that preexisting TCRs that cross-react with influenza A variants could limit the spread of newly emerging viral strains. According to the authors, unraveling the molecular basis of such cross-reactivity could help design a universal vaccine for influenza. — S.R.

Climate change and biodiversity in mountain streams

Water temperature scenario for a 222,000-km stream network used to identify refugia for aquatic biodiversity.

Previous studies have predicted that climate change is likely to cause extinction of many species native to mountain environments. Aquatic species that require cold water are thought to be particularly at risk, but predictions for these species rest on sparse datasets and untested assumptions about the relationship between air and water temperatures. Daniel Isaak et al. (pp. 4374–4379) estimated the historical warming trends throughout the 222,000-km network of rivers and streams in the northwestern United States using temperature measurements from more than 16,000 monitoring sites. During the years 1968 to 2011, when air temperatures warmed by 0.21 °C/decade on average, water temperatures rose by only 0.101 °C/decade. Climate zones moved at a median velocity of 1.07 km/decade during this same period, more than an order of magnitude slower than velocities reported for terrestrial and marine environments. The authors found that several cold-water vertebrate species occupied habitats characterized by particularly slow climate velocities and that three species of conservation concern—bull trout, cutthroat trout, and tailed frogs—inhabited environments with climate velocities slower than 0.5 km/decade. According to the authors, the results suggest that mountain streams might buffer species against the effects of a warming climate, and that biodiversity in such climate refuge streams could persist throughout the coming century. — B.D.