SciCombinator

Discover the most talked about and latest scientific content & concepts.

11

Levels of physical activity and variation in physical activity and sedentary time by place and person in European children and adolescents are largely unknown. The objective of the study was to assess the variations in objectively measured physical activity and sedentary time in children and adolescents across Europe.

11

Interleukin-2 (IL-2) is a small α-helical cytokine that regulates immune cell homeostasis through its recruitment to a high-affinity heterotrimeric receptor complex (IL-2Rα/IL-2Rβ/γc). IL-2 has been shown to have therapeutic efficacy for immune diseases by preferentially expanding distinct T cell compartments, and several regulatory T cell (Treg)-biasing anti-IL-2 antibodies have been developed for combination therapies. The conformational plasticity of IL-2 plays an important role in its biological actions by modulating the strength of receptor and drug interactions. Through an NMR analysis of milliseconds-timescale dynamics of free mouse IL-2 (mIL-2), we identify a global transition to a sparse conformation which is regulated by an α-helical capping “switch” at the loop between the A and B helices (AB loop). Binding to either an anti-mouse IL-2 monoclonal antibody (mAb) or a small molecule inhibitor near the loop induces a measurable response at the core of the structure, while locking the switch to a single conformation through a designed point mutation leads to a global quenching of core dynamics accompanied by a pronounced effect in mAb binding. By elucidating key details of the long-range allosteric communication between the receptor binding surfaces and the core of the IL-2 structure, our results offer a direct blueprint for designing precision therapeutics targeting a continuum of conformational states.

10

Annotation of cell identity is an essential process in neuroscience that allows comparison of cells, including that of neural activities across different animals. In Caenorhabditis elegans, although unique identities have been assigned to all neurons, the number of annotatable neurons in an intact animal has been limited due to the lack of quantitative information on the location and identity of neurons.

10

Of the 70,237 drug overdose deaths in the United States in 2017, approximately two thirds (47,600) involved an opioid (1). In recent years, increases in opioid-involved overdose deaths have been driven primarily by deaths involving synthetic opioids other than methadone (hereafter referred to as synthetic opioids) (1). CDC analyzed changes in age-adjusted death rates from 2017 to 2018 involving all opioids and opioid subcategories* by demographic characteristics, county urbanization levels, U.S. Census region, and state. During 2018, a total of 67,367 drug overdose deaths occurred in the United States, a 4.1% decline from 2017; 46,802 (69.5%) involved an opioid (2). From 2017 to 2018, deaths involving all opioids, prescription opioids, and heroin decreased 2%, 13.5%, and 4.1%, respectively. However, deaths involving synthetic opioids increased 10%, likely driven by illicitly manufactured fentanyl (IMF), including fentanyl analogs (1,3). Efforts related to all opioids, particularly deaths involving synthetic opioids, should be strengthened to sustain and accelerate declines in opioid-involved deaths. Comprehensive surveillance and prevention measures are critical to reducing opioid-involved deaths, including continued surveillance of evolving drug use and overdose, polysubstance use, and the changing illicit drug market; naloxone distribution and outreach to groups at risk for IMF exposure; linkage to evidence-based treatment for persons with substance use disorders; and continued partnerships with public safety.

10

Once thought to be the magical horn of a unicorn, narwhal tusks are one of the most charismatic structures in biology. Despite years of speculation, little is known about the tusk’s function, because narwhals spend most of their lives hidden underneath the Arctic ice. Some hypotheses propose that the tusk has sexual functions as a weapon or as a signal. By contrast, other hypotheses propose that the tusk functions as an environmental sensor. Since assessing the tusks function in nature is difficult, we can use the morphological relationships of tusk size with body size to understand this mysterious trait. To do so, we collected morphology data on 245 adult male narwhals over the course of 35 years. Based on the disproportional growth and large variation in tusk length we found, we provide the best evidence to date that narwhal tusks are indeed sexually selected. By combining our results on tusk scaling with known material properties of the tusk, we suggest that the narwhal tusk is a sexually selected signal that is used during male-male contests.

10

The Pedra de Fogo Formation in the Parnaíba Basin of northeastern Brazil hosts a recently discovered lacustrine fauna and provides the only known record of the Captorhinidae in South America. Here, new captorhinid remains from this unit are described. Two partial mandibles, including one formerly ascribed to the genus Captorhinus, are here referred to Captorhinikos sp. a genus previously described from North America. The natural mould of a large mandible probably represents a new taxon within the captorhinid subclade Moradisaurinae, and a small skull roof is regarded as Captorhinidae indet. Captorhinids are generally considered to have been herbivores or omnivores. The Pedra de Fogo captorhinids likely played an important ecological role as primary consumers in the palaeoenvironment of this geological unit, which is also known for its extensive record of petrified forests. The new finds reinforce the close relationships between the continental faunas of palaeotropical western Gondwana and palaeoequatorial North America during the Cisuralian.

10

The soundscape composition of temperate freshwater habitats is poorly understood. Our goal was to document the occurrence of biological and anthropogenic sounds in freshwater habitats over a large (46,000 km2) area along the geographic corridors of five major river systems in North America (Connecticut, Kennebec, Merrimack, Presumpscot, and Saco). The underwater soundscape was sampled in 19 lakes, 17 ponds, 20 rivers and 20 streams, brooks and creeks that were grouped into broad categories (brook/creek, pond/lake, and river). Over 7,000 sounds were measured from 2,750 minutes of recording in 173 locations over a five-week period in the spring of 2008. Sounds were classified into major anthropophony (airplane, boat, traffic, train and other noise) and biophony (fish air movement, also known as air passage, other fish, insect-like, bird, and other biological) categories. The three most significant findings in this study are: 1) freshwater habitats in the New England region of North America contain a diverse array of unidentified biological sounds; 2) fish air movement sounds constitute a previously unrecognized important component of the freshwater soundscape, occurring at more locations (39%) and in equal abundance than other fish sounds; and 3) anthropogenic noises dominate the soundscape accounting for 92% of the soundscape by relative percent time. The high potential for negative impacts of the anthropophony on freshwater soundscapes is suggested by the spectral and temporal overlap of the anthropophony with the biophony, the higher received sound levels of the anthropophony relative to the biophony, and observations of a significant decline in the occurrence, number, percent time, and diversity of the biophony among locations with higher ambient received levels. Our poor understanding of the biophony of freshwater ecosystems, together with an apparent high temporal exposure to anthropogenic noise across all habitats, suggest a critical need for studies aimed at identification of biophonic sound sources and assessment of potential threats from anthropogenic noises.

9

The Indian Ocean Dipole (IOD) affects climate and rainfall across the world, and most severely in nations surrounding the Indian Ocean1-4. The frequency and intensity of positive IOD events increased during the twentieth century5 and may continue to intensify in a warming world6. However, confidence in predictions of future IOD change is limited by known biases in IOD models7 and the lack of information on natural IOD variability before anthropogenic climate change. Here we use precisely dated and highly resolved coral records from the eastern equatorial Indian Ocean, where the signature of IOD variability is strong and unambiguous, to produce a semi-continuous reconstruction of IOD variability that covers five centuries of the last millennium. Our reconstruction demonstrates that extreme positive IOD events were rare before 1960. However, the most extreme event on record (1997) is not unprecedented, because at least one event that was approximately 27 to 42 per cent larger occurred naturally during the seventeenth century. We further show that a persistent, tight coupling existed between the variability of the IOD and the El Niño/Southern Oscillation during the last millennium. Indo-Pacific coupling was characterized by weak interannual variability before approximately 1590, which probably altered teleconnection patterns, and by anomalously strong variability during the seventeenth century, which was associated with societal upheaval in tropical Asia. A tendency towards clustering of positive IOD events is evident in our reconstruction, which-together with the identification of extreme IOD variability and persistent tropical Indo-Pacific climate coupling-may have implications for improving seasonal and decadal predictions and managing the climate risks of future IOD variability.

9

The Anthropocene has brought substantial change to ocean ecosystems, but whether this age will bring more or less marine disease is unknown. In recent years, the accelerating tempo of epizootic and zoonotic disease events has made it seem as if disease is on the rise. Is this apparent increase in disease due to increased observation and sampling effort, or to an actual rise in the abundance of parasites and pathogens? We examined the literature to track long-term change in the abundance of two parasitic nematode genera with zoonotic potential: Anisakis spp. and Pseudoterranova spp. These anisakid nematodes cause the disease anisakidosis and are transmitted to humans in undercooked and raw marine seafood. A total of 123 papers published between 1967 and 2017 met our criteria for inclusion, from which we extracted 755 host-parasite-location-year combinations. Of these, 69.7% concerned Anisakis spp. and 30.3% focused on Pseudoterranova spp. Meta-regression revealed an increase in Anisakis spp. abundance (average number of worms/fish) over a 53 year period from 1962 to 2015 and no significant change in Pseudoterranova spp. abundance over a 37 year period from 1978 to 2015. Standardizing changes to the period of 1978-2015, so that results are comparable between genera, we detected a significant 283-fold increase in Anisakis spp. abundance and no change in the abundance of Pseudoterranova spp. This increase in Anisakis spp. abundance may have implications for human health, marine mammal health, and fisheries profitability.

9

Rapid antibiotic susceptibility testing (AST) for Neisseria gonorrhoeae (Ng) is critically needed to counter widespread antibiotic resistance. Detection of nucleic acids in genotypic AST can be rapid, but it has not been successful for β-lactams (the largest antibiotic class used to treat Ng). Rapid phenotypic AST for Ng is challenged by the pathogen’s slow doubling time and the lack of methods to quickly quantify the pathogen’s response to β-lactams. Here, we asked two questions: (1) Is it possible to use nucleic acid quantification to measure the β-lactam susceptibility phenotype of Ng very rapidly, using antibiotic-exposure times much shorter than the 1- to 2-h doubling time of Ng? (2) Would such short-term antibiotic exposures predict the antibiotic resistance profile of Ng measured by plate growth assays over multiple days? To answer these questions, we devised an innovative approach for performing a rapid phenotypic AST that measures DNA accessibility to exogenous nucleases after exposure to β-lactams (termed nuclease-accessibility AST [nuc-aAST]). We showed that DNA in antibiotic-susceptible cells has increased accessibility upon exposure to β-lactams and that a judiciously chosen surfactant permeabilized the outer membrane and enhanced this effect. We tested penicillin, cefixime, and ceftriaxone and found good agreement between the results of the nuc-aAST after 15-30 min of antibiotic exposure and the results of the gold-standard culture-based AST measured over days. These results provide a new pathway toward developing a critically needed phenotypic AST for Ng and additional global-health threats.