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Proceedings of the National Academy of Sciences of the United States of America logoLink to Proceedings of the National Academy of Sciences of the United States of America
. 2016 Mar 15;113(11):2793–2795. doi: 10.1073/iti1116113

Assessing emergence of SARS-like epidemic viruses

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Evaluating emergence of SARS-like epidemic viruses. Image courtesy of iStockphoto/EdStock.

The precise likelihood of emergence of zoonotic coronaviruses with epidemic potential similar to severe acute respiratory coronavirus (SARS-CoV) remains unclear. Using a reverse genetics approach, Vineet Menachery et al. (pp. 3048–3053) constructed WIV1-CoV, a previously described bat coronavirus that can infect humans using the human angiotensin converting enzyme 2 (ACE2), as well as a hybrid virus containing the WIV1-CoV surface spike protein in a SARS-CoV backbone adapted for murine infection. The authors found that both engineered viruses robustly infected human lung airway epithelial cultures, suggesting that the WIV1-CoV spike protein can mediate human infection without further molecular adaptations. Compared with SARS-CoV, WIV1-CoV displayed weakened replication in wild-type mice. Although WIV1-CoV replication improved in mice engineered to express human ACE2, it failed to reach levels comparable to that of the epidemic SARS-CoV. Importantly, a broadly neutralizing monoclonal antibody panel derived from phage display and B cells of patients infected with SARS-CoV protected mice against potentially lethal exposure to both SARS-CoV and wild-type WIV1-CoV. Compared with mock-treated mice, mice that were administered the protective antibodies harbored no detectable virus in the lungs. However, a double-inactivated SARS-CoV candidate vaccine, previously found to be effective in young mice, failed to protect mice against a WIV1-CoV challenge. According to the authors, compared with SARS-CoV, WIV1-CoV might pose a diminished epidemic threat to humans, warranting studies on its zoonotic potential. — P.N.

Estimating past global sea level changes

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Coastal wetland in Newfoundland, Canada, a location that harbors a record of sea level for the past 2,000 years.

Previous estimates of past changes in global sea level (GSL) over the Common Era have not been based on statistical syntheses of global proxy databases. Robert Kopp et al. (pp. E1434–E1441) estimated GSL change over the Common Era using a spatiotemporal statistical hierarchical model and regional sea level reconstructions from 24 locations. The authors found that over the Common Era prior to the 20th century, the amplitude of variation in GSL was very likely between 7 cm and 11 cm. Between 1000 and 1400 CE, GSL fell an average of 0.2 mm/year, coinciding with a global mean temperature decrease of approximately 0.2 °C. The authors’ reconstruction showed that it is extremely likely that the GSL rise in the 20th century was faster than during any previous century going back to 800 BCE. Using their GSL reconstruction to create a model relating the rate of GSL change to the global mean temperature, the authors estimated the anthropogenic contribution to 20th century GSL rise. The model predicted that, without anthropogenic warming, it is extremely likely that 20th century GSL rise would have been less than half of the observed rise. According to the authors, when the same model is used to project 21st century GSL change, the projections reduce the discrepancy between process-based and semiempirical methods of generating such projections. — B.D.

Plant biomarkers hint at early human habitat

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A grassland oasis can offer freshwater and shelter.

Fossil evidence showing how early humans coexisted spatially with critical plant and water resources is scant. As a result, how such local resources affected early human evolution remains unclear. To study the meter-scale spatial distribution of these resources, Clayton Magill et al. (pp. 2874–2879) excavated 71 buried soil samples across a 25,000-square-meter area at a nearly 2-million-year-old Olduvai Gorge archaeological site. Different types of plants each have their own characteristic chemical biomarkers preserved in the soil. The authors analyzed these biomarkers to distinguish between cooccurring plant types. The biomarker evidence indicated a varied landscape containing different types of vegetation, including the presence of a woodland thicket near a small freshwater wetland, surrounded by open grasslands. This finding suggests that early humans living at Olduvai Gorge had reliable access to potable water, edible plants, and aquatic animals. The thicketed area delineated by biomarkers also contained butchered animal bones and early human remains. According to the authors, early humans may have brought animal remains and food from the surrounding grasslands or wetlands to a wooded habitat, which may have provided protection and access to freshwater. — S.R.

Host immunity, climate warming, and parasite infections

Climate warming is predicted to increase the risk of parasite infections, but how this link is influenced by variations in host immunity remains unclear. Andrea Mignatti et al. (pp. 2970–2975) explored the disease dynamics of two soil-transmitted gastrointestinal helminths of rabbits, Trichostrongylus retortaeformis and Graphidum strigosum, sampled monthly between 1977 and 2002 in Scotland. The availability of infective parasites in pasture increases with rising temperature and humidity, and the authors found that parasite accumulation in rabbits depended on the host immune response to these helminth worms. Because G. strigosum infection is not controlled by the rabbit immune response, the intensity of the parasite infection increases with warming, leading to significant accumulation of G. strigosum in the host population, with most of the parasite load in adult rabbits. In contrast, T. retortaeformis infection is controlled by the rabbit immune system, offsetting the effects of climate and resulting in a relatively constant intensity of infection over time in the rabbit population. However, climate warming shifted the seasonal peak of T. retortaeformis infection toward young hosts lacking a strong immune response, demonstrating how long-term climate warming can affect the parasite’s seasonal changes in infection and transmission. The study demonstrates how interactions between climate change and host immunity can affect parasite infections, according to the authors. — S.R.

Dopamine fluctuations in alcohol addiction

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Dynamic regulation of dopamine in alcohol dependence.

The cycle of intoxication and withdrawal that characterizes chronic alcoholism induces changes in the brain’s reward pathway, which relies on the neurotransmitter dopamine. Natalie Hirth et al. (pp. 3024–3029) investigated changes in dopamine regulation that occur in alcohol-dependent individuals during periods of abstinence. The authors compared ligand binding by three different dopamine-binding molecules in postmortem human brain tissue samples of heavy alcohol drinkers with samples from those who drank little. Binding to the D2-like receptor was similar in heavy and light drinkers, but ligand binding to the D1 receptor and dopamine transporter was reduced in heavy drinkers. The results indicate a hyperdopaminergic state, marked by high levels of dopamine, associated with alcoholism. The authors showed similar effects in a rat model of alcoholism. Immediately after withdrawal from alcohol, brain tissue samples from the rats indicated low levels of dopamine, but dopamine level indicators increased during periods of abstinence from alcohol. The increased dopamine levels were associated with hyperactivity and enhanced alcohol seeking in the rats. The authors suggest that levels of dopamine in the brain decrease during the immediate withdrawal from alcohol and later increase to a hyperdopaminergic state during extended abstinence. Uncovering behaviors associated with the increased dopamine levels could identify ways to prevent relapse, according to the authors. — T.H.D.

Seasonality in brain function

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Seasonal variations in brain responses to two cognitive tasks, where the black lines represent the mean values.

Mood changes have been linked to seasonality, but little is known about how other human brain functions may vary according to the seasons. Christelle Meyer et al. (pp. 3066–3071) measured the cognitive brain function of 28 volunteers at different times of the year. For each testing period, each participant spent 5 days in the laboratory, devoid of seasonal cues, such as daylight, and without access to the external world. At the end of the 5-day period, the authors used functional MRI to assess sustained attention and higher executive function in two separate tasks. Performance on both tasks remained constant, but the brain resources used to complete each task changed with the seasons. Brain activity related to sustained attention peaked in June near the summer solstice and was lowest near the winter solstice. In contrast, working memory-related brain activity, a higher-order task, peaked in fall and was lower near the spring equinox. The authors report that these results did not correlate with endocrine measures, such as melatonin, or neurophysiological measures of alertness and sleep. According to the authors, in addition to daily circadian rhythms, certain brain functions may be more seasonal than previously appreciated and that seasonal rhythmicity may be specific to the cognitive process. — T.H.D.


Articles from Proceedings of the National Academy of Sciences of the United States of America are provided here courtesy of National Academy of Sciences

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