The use of any tobacco product by youths is unsafe, including electronic cigarettes (e-cigarettes) (1). Most e-cigarettes contain nicotine, which is highly addictive, can harm the developing adolescent brain, and can increase risk for future addiction to other drugs (1). E-cigarette use has increased considerably among U.S. youths since 2011 (1,2). Multiple factors have contributed to this increase, including youth-appealing flavors and product innovations (1-3). Amid the widespread use of e-cigarettes and popularity of certain products among youths, on February 6, 2020, the Food and Drug Administration (FDA) implemented a policy prioritizing enforcement against the manufacture, distribution, and sale of certain unauthorized flavored prefilled pod or cartridge-based e-cigarettes (excluding tobacco or menthol).
Stinging trees from Australasia produce remarkably persistent and painful stings upon contact of their stiff epidermal hairs, called trichomes, with mammalian skin. Dendrocnide-induced acute pain typically lasts for several hours, and intermittent painful flares can persist for days and weeks. Pharmacological activity has been attributed to small-molecule neurotransmitters and inflammatory mediators, but these compounds alone cannot explain the observed sensory effects. We show here that the venoms of Australian Dendrocnide species contain heretofore unknown pain-inducing peptides that potently activate mouse sensory neurons and delay inactivation of voltage-gated sodium channels. These neurotoxins localize specifically to the stinging hairs and are miniproteins of 4 kDa, whose 3D structure is stabilized in an inhibitory cystine knot motif, a characteristic shared with neurotoxins found in spider and cone snail venoms. Our results provide an intriguing example of inter-kingdom convergent evolution of animal and plant venoms with shared modes of delivery, molecular structure, and pharmacology.
Until treatment and vaccine for coronavirus disease-2019 (COVID-19) becomes widely available, other methods of reducing infection rates should be explored. This study used a retrospective, observational analysis of deidentified tests performed at a national clinical laboratory to determine if circulating 25-hydroxyvitamin D (25(OH)D) levels are associated with severe acute respiratory disease coronavirus 2 (SARS-CoV-2) positivity rates. Over 190,000 patients from all 50 states with SARS-CoV-2 results performed mid-March through mid-June, 2020 and matching 25(OH)D results from the preceding 12 months were included. Residential zip code data was required to match with US Census data and perform analyses of race/ethnicity proportions and latitude. A total of 191,779 patients were included (median age, 54 years [interquartile range 40.4-64.7]; 68% female. The SARS-CoV-2 positivity rate was 9.3% (95% C.I. 9.2-9.5%) and the mean seasonally adjusted 25(OH)D was 31.7 (SD 11.7). The SARS-CoV-2 positivity rate was higher in the 39,190 patients with “deficient” 25(OH)D values (<20 ng/mL) (12.5%, 95% C.I. 12.2-12.8%) than in the 27,870 patients with "adequate" values (30-34 ng/mL) (8.1%, 95% C.I. 7.8-8.4%) and the 12,321 patients with values ≥55 ng/mL (5.9%, 95% C.I. 5.5-6.4%). The association between 25(OH)D levels and SARS-CoV-2 positivity was best fitted by the weighted second-order polynomial regression, which indicated strong correlation in the total population (R2 = 0.96) and in analyses stratified by all studied demographic factors. The association between lower SARS-CoV-2 positivity rates and higher circulating 25(OH)D levels remained significant in a multivariable logistic model adjusting for all included demographic factors (adjusted odds ratio 0.984 per ng/mL increment, 95% C.I. 0.983-0.986; p<0.001). SARS-CoV-2 positivity is strongly and inversely associated with circulating 25(OH)D levels, a relationship that persists across latitudes, races/ethnicities, both sexes, and age ranges. Our findings provide impetus to explore the role of vitamin D supplementation in reducing the risk for SARS-CoV-2 infection and COVID-19 disease.
The Carnian Pluvial Episode (Late Triassic) was a time of global environmental changes and possibly substantial coeval volcanism. The extent of the biological turnover in marine and terrestrial ecosystems is not well understood. Here, we present a meta-analysis of fossil data that suggests a substantial reduction in generic and species richness and the disappearance of 33% of marine genera. This crisis triggered major radiations. In the sea, the rise of the first scleractinian reefs and rock-forming calcareous nannofossils points to substantial changes in ocean chemistry. On land, there were major diversifications and originations of conifers, insects, dinosaurs, crocodiles, lizards, turtles, and mammals. Although there is uncertainty on the precise age of some of the recorded biological changes, these observations indicate that the Carnian Pluvial Episode was linked to a major extinction event and might have been the trigger of the spectacular radiation of many key groups that dominate modern ecosystems.
To examine the under-reporting of pharmaceutical company payments to patient organisations by donors and recipients.
Sleep serves disparate functions, most notably neural repair, metabolite clearance and circuit reorganization. Yet the relative importance remains hotly debated. Here, we create a novel mechanistic framework for understanding and predicting how sleep changes during ontogeny and across phylogeny. We use this theory to quantitatively distinguish between sleep used for neural reorganization versus repair. Our findings reveal an abrupt transition, between 2 and 3 years of age in humans. Specifically, our results show that differences in sleep across phylogeny and during late ontogeny (after 2 or 3 years in humans) are primarily due to sleep functioning for repair or clearance, while changes in sleep during early ontogeny (before 2 or 3 years) primarily support neural reorganization and learning. Moreover, our analysis shows that neuroplastic reorganization occurs primarily in REM sleep but not in NREM. This developmental transition suggests a complex interplay between developmental and evolutionary constraints on sleep.
One of the features distinguishing SARS-CoV-2 from its more pathogenic counterpart SARS-CoV is the presence of premature stop codons in its ORF3b gene. Here, we show that SARS-CoV-2 ORF3b is a potent interferon antagonist, suppressing the induction of type I interferon more efficiently than its SARS-CoV ortholog. Phylogenetic analyses and functional assays reveal that SARS-CoV-2-related viruses from bats and pangolins also encode truncated ORF3b gene products with strong anti-interferon activity. Furthermore, analyses of approximately 17,000 SARS-CoV-2 sequences identify a natural variant in which a longer ORF3b reading frame was reconstituted. This variant was isolated from two patients with severe disease and further increased the ability of ORF3b to suppress interferon induction. Thus, our findings not only help to explain the poor interferon response in COVID-19 patients but also describe the emergence of natural SARS-CoV-2 quasispecies with an extended ORF3b gene that may potentially affect COVID-19 pathogenesis.
The COVID-19 virus pandemic has caused a significant number of deaths worldwide. If the prevalence of the infection continues to grow, this could impact life expectancy. This paper provides first estimates of the potential direct impact of the COVID-19 pandemic on period life expectancy.
To combat SARS-CoV-2 and any unknown emerging pathogens in the future, the development of a rapid and effective method to generate high-affinity antibodies or antibody-like proteins is of critical importance. We here report a high-speed in vitro selection of multiple high-affinity antibody-like proteins against various targets including the SARS-CoV-2 spike protein. The sequences of monobodies against the SARS-CoV-2 spike protein were successfully procured within only four days. Furthermore, the obtained monobody efficiently captured SARS-CoV-2 particles from the nasal swab samples of patients and exhibited a high neutralizing activity against SARS-CoV-2 infection (IC50 = 0.5 nM). The high-speed in vitro selection of antibody-like proteins would be useful for the rapid development of a detection method and a neutralizing protein against a virus responsible for an ongoing, and possibly a future, pandemic.
The COVID-19 pandemic is a collective stressor unfolding over time, yet rigorous published empirical studies addressing mental health consequences of COVID-19 among large probability-based national samples are rare. Between 3/18-4/18/20, during an escalating period of illness and death in the United States, we assessed acute stress, depressive symptoms and direct, community, and media-based exposures to COVID-19 in three consecutive representative samples across three 10-day periods (total N=6,514) from the U.S. probability-based nationally representative NORC AmeriSpeak panel. Acute stress and depressive symptoms increased significantly over time as COVID-19 deaths increased across the U.S. Pre-existing mental and physical health diagnoses, daily hours of COVID-19-related media exposure, exposure to conflicting COVID-19 information in media, and secondary stressors were all associated with acute stress and depressive symptoms. Results have implications for targeting of public health interventions and risk communication efforts to promote community resilience as the pandemic waxes and wanes over time.