COVID-19 and “natural” experiments arising from physical distancing: a hypothetical case study from chronobiology

ABSTRACT

With countless “natural” experiments triggered by the COVID-19-associated physical distancing, one key question comes from chronobiology: “When confined to homes, how does the reduced exposure to natural daylight arising from the interruption of usual outdoor activities plus lost temporal organization ordinarily provided from workplaces and schools affect the circadian timing system (the internal 24 h clock) and, consequently, health of children and adults of all ages?” Herein, we discuss some ethical and scientific facets of exploring such natural experiments by offering a hypothetical case study of circadian biology.     

Competition at the soybean V6 stage affects root morphology and biochemical composition

• The experiment was conducted in the 2016/17 crop season in a greenhouse at Passo Fundo University, Brazil. We hypothesised that the morphological characteristics and biochemical and anatomical composition of soybean roots and shoots, when competing with weeds during different growth periods, are negatively affected, so current concepts of competition between plants should also consider changes in plant roots.
• The soybean cultivar P 95R51 and horseweed (Conyza bonariensis) were used. The treatments consisted of the presence or absence of weeds during different coexistence periods of soybean with horseweed. The periods were V0–V3, V0–V6, V0–R2, V3–R6, V6–R6 and R2–R6, where V0 was the date of soybean sowing and V3, V6, R2 and R6 were phenological stages of the crop. Two fresh roots were used to examine morphological traits. Four roots were used for quantification of dry matter and secondary metabolites.
• Root length was reduced by 21%, 14% and 20% when competing with a weed in the V0–V3, V0–V6 and R2–R6 coexistence periods, respectively. Total phenol content in the V0–V6 and V0–R2 periods was reduced when plants were in competition with weeds; a similar trend was found for flavonoids in the V0–V6 period.
• Soybean–horseweed competition from crop emergence to the V6 stage, in general, affects shoot and root morphological traits and the biochemical composition of the soybean roots. The presence of horseweed at the V3, V6 and R2 stages does not negatively alter the traits evaluated. Root anatomical composition is not modified during all coexistence periods with horseweed.

     

Spliceosome-targeted therapies trigger an antiviral immune response in triple-negative breast cancer

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The antigenic anatomy of SARS-CoV-2 receptor binding domain

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BET inhibition blocks inflammation-induced cardiac dysfunction and SARS-CoV-2 infection

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Synthesis of the Mechanisms of Opioid Tolerance: Do We Still Say NO?

The use of morphine as a first-line agent for moderate-to-severe pain is limited by the development of analgesic tolerance. Initially opioid receptor desensitization in response to repeated stimulation, thought to underpin the establishment of tolerance, was linked to a compensatory increase in adenylate cyclase responsiveness. The subsequent demonstration of cross-talk between N-methyl-d-aspartate (NMDA) glutamate receptors and opioid receptors led to the recognition of a role for nitric oxide (NO), wherein blockade of NO synthesis could prevent tolerance developing. Investigations of the link between NO levels and opioid receptor desensitization implicated a number of events including kinase recruitment and peroxynitrite-mediated protein regulation. Recent experimental advances and the identification of new cellular constituents have expanded the potential signaling candidates to include unexpected, intermediary compounds not previously linked to this process such as zinc, histidine triad nucleotide-binding protein 1 (HINT1), micro-ribonucleic acid (mi-RNA) and regulator of G protein signaling Z (RGSZ). A further complication is a lack of consistency in the protocols used to create tolerance, with some using acute methods measured in minutes to hours and others using days. There is also an emphasis on the cellular changes that are extant only after tolerance has been established. Although a review of the literature demonstrates a lack of spatio-temporal detail, there still appears to be a pivotal role for nitric oxide, as well as both intracellular and intercellular cross-talk. The use of more consistent approaches to verify these underlying mechanism(s) could provide an avenue for targeted drug development to rescue opioid efficacy.