Notes

Class Any Scavenger Receptor-Mediated Double-Stranded RNA Internalization Is Separate from Natural Antiviral Signaling and Does Not Demand Phosphatidylinositol 3-Kinase Action.
Drought at flowering and grain filling greatly reduces maize (Zea mays) yield. Climate change is causing earlier and longer lasting periods of drought, which affect the growth of multiple maize organs throughout development. To study how long periods of water deficit impact the dynamic nature of growth, and to determine how these relate to reproductive drought, we employed a high-throughput phenotyping platform featuring precise irrigation, imaging systems, and image-based biomass estimations. Prolonged drought resulted in a reduction of growth rate of individual organs-though an extension of growth duration partially compensated for this-culminating in lower biomass and delayed flowering. However, long periods of drought did not affect the highly organized succession of maximal growth rates of the distinct organs, i.e., leaves, stems, and ears. Two drought treatments negatively affected distinct seed yield components prolonged drought mainly reduced the number of spikelets, and drought during the reproductive period increased the anthesis-silking interval. The identification of these divergent biomass and yield components, which were affected by the shift in duration and intensity of drought, will facilitate trait-specific breeding towards future climate-resilient crops.In tropical and subtropical countries four dengue viruses (DENV) produce mild disease and a potentially fatal vascular permeability syndrome. Unique antigenic and biological properties of DENVs contribute to vaccine development delays. Three tissue culture-based tetravalent candidate dengue vaccines have advanced to phase 3 clinical testing. Sanofi-Pasteur's chimeric yellow fever tetravalent dengue vaccine, Dengvaxia, licensed in 19 dengue-endemic countries, Europe and USA, partially protects seropositives but sensitizes some seronegatives to breakthrough severe hospitalized dengue. During two years of phase 3, Takeda's TAK 003, a chimeric DENV 2 tetravalent vaccine, protected against DENV 2 but was less protective against other DENVs. In seronegative adults, one dose of a tetravalent non-structural deletion mutant vaccine developed by US NIAID protected seronegative humans against challenge with DENVs 2 and 3. This vaccine is in late phase 3. This experience suggests nearly-whole DENV genomes are required to achieve balanced and sustained protective immunity.Recently, it has been proposed that the doses received from 133Xe released during the accident in 1979 at the Three Mile Island (TMI) plant in Pennsylvania were much higher than has been conventionally assessed, due to a gross underestimation of the relative biological effectiveness of electrons from beta-particle-emitting radionuclides within the body. The central evidence cited in support of this proposal was the doses derived from cytogenetic analyses of blood sampled in the mid-1990s from people living near TMI at the time of the accident. However, the chromosome aberration data show a marked discrepancy in biodosimetric estimates evaluated from the frequencies of stable translocations and unstable dicentrics (corrected for temporal attenuation), strongly suggesting that exposures to clastogenic agents occurred long after the TMI accident. Few details have been reported on the people providing the blood samples and how they were selected for study. Crucially, this lack of information includes the distributions in the exposed and control groups of age at sampling, which is a critical factor in interpreting translocation data. Contrary to the recent claim, these cytogenetic data offer no support to the suggestion of a serious underestimation of internal doses from beta particles or from 133Xe discharged during the TMI accident.
Psoriatic arthritis (PsA) is associated with bone erosion and inflammation-induced bone loss, which are mediated by osteoclasts and modulated by inflammatory cytokines. Apremilast (a selective phosphodiesterase 4 inhibitor) is efficacious in PsA and acts by inhibiting cytokine production. However, there are no direct data informing whether and how apremilast affects osteoclast formation in humans.

Osteoclastogenic cytokine production by activated human peripheral blood mononuclear cells (PBMCs) was measured in the presence and absence of apremilast. Effects of apremilast on osteoclast differentiation were tested (i) in co-cultures of activated PBMCs and human CD14+ blood monocytes as well as (ii) in CD14+ blood monocytes stimulated with activated-PBMCs supernatant, TNF or IL-17A. Bone resorption was measured on OsteoAssay plates. Effects of apremilast on ex vivo osteoclast differentiation were compared in PsA, pre-PsA and psoriasis patients as well as in healthy controls.

Apremilast significantly impairlastogenesis. These data provide initial evidence that apremilast has the potential to provide a direct bone protective effect in PsA.
Sequencing of the SARS-CoV-2 viral genome from patient samples is an important epidemiological tool for monitoring and responding to the pandemic, including the emergence of new mutations in specific communities.

SARS-CoV-2 genomic sequences were generated from positive samples collected, along with epidemiological metadata, at a walk-up, rapid testing site in the Mission District of San Francisco, California during November 22-December 1, 2020 and January 10-29, 2021. Secondary household attack rates and mean sample viral load were estimated and compared across observed variants.

A total of 12,124 tests were performed yielding 1,099 positives. From these, 928 high quality genomes were generated. Certain viral lineages bearing spike mutations, defined in part by L452R, S13I, and W152C, comprised 54.4% of the total sequences from January, compared to 15.7% in November. selleck compound Household contacts exposed to the "California" or "West Coast" variants (B.1.427 and B.1.429) were at higher risk of infection compared to household contacts exposed to lineages lacking these variants (0.36 vs 0.29, RR=1.28; 95% CI1.00-1.64). The reproductive number was estimated to be modestly higher than other lineages spreading in California during the second half of 2020. Viral loads were similar among persons infected with West Coast versus non-West Coast strains, as was the proportion of individuals with symptoms (60.9% vs 64.3%).

The increase in prevalence, relative household attack rates, and reproductive number are consistent with a modest transmissibility increase of the West Coast variants.
The increase in prevalence, relative household attack rates, and reproductive number are consistent with a modest transmissibility increase of the West Coast variants.
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