Thurstonkinney4713

Large animal models such as rhesus and cynomologus macaques and African green monkeys are critical to understanding how the immune system responds to SARS-CoV-2 infection because they are considered to be the most similar to humans. These models are considered the gold standard for assessing vaccine efficacy and protection, and recapitulate the initial cytokine surge, immune cell infiltration into the lung, certain aspects of thrombosis, and the antibody and T-cell response to the virus. In this review, we discuss both small and large animal model studies previously used in SARS-CoV-2 research that may be useful in elucidating the immunological contributions to hallmark syndromes observed with COVID-19.The production of seed in flowering plants is complicated by the need to first invest in reproductive shoots, inflorescences, flowers and fruit. Furthermore, in many species, it will be months between plants generating flowers and setting seed. How can plants therefore produce an optimal seed-set relative to environmental resources when the 'reproductive architecture' that supports seed-set needs to be elaborated so far in advance? Here, we address this question by investigating the spatio-temporal control of reproductive architecture in Arabidopsis (Arabidopsis thaliana) and Brassica napus. We show that resource- and resource-related signals such as substrate volume play a key role in determining the scale of reproductive effort, and that this is reflected in the earliest events in reproductive development, which broadly predicts the subsequent reproductive effort. We show that a series of negative feedbacks both within and between developmental stages prevent plants from over-committing to early stages of development. These feedbacks create a highly plastic, homeostatic system in which additional organs can be produced in the case of reproductive failure elsewhere in the system. We propose that these feedbacks represent an 'integrated dominance' mechanism that allows resource use to be correctly sequenced between developmental stages to optimise seed set.Recent studies in Arabidopsis (Arabidopsis thaliana) have reported conflicting roles for NAC DOMAIN CONTAINING PROTEIN 17 (ANAC017), a transcription factor regulating mitochondria-to-nuclear signalling, and its closest paralog NAC DOMAIN CONTAINING PROTEIN 16 (ANAC016), in leaf senescence. By synchronising senescence in individually darkened leaves of knock-out and overexpressing mutants from these contrasting studies, we demonstrate that elevated ANAC017 expression consistently causes accelerated senescence and cell death. A time-resolved transcriptome analysis revealed that senescence-associated pathways such as autophagy are not constitutively activated in ANAC017 overexpression lines, but require a senescence-stimulus to trigger accelerated induction. ANAC017 transcript and ANAC017-target genes are constitutively upregulated in ANAC017 overexpression lines, but surprisingly show a transient 'super-induction' one day after senescence-induction. This induction of ANAC017 and its target genes is observed during the later stages of age-related and dark induced senescence, indicating the ANAC017 pathway is also activated in natural senescence. In contrast, knockout mutants of ANAC017 showed lowered senescence-induced induction of ANAC017 target genes during the late stages of dark-induced senescence. Finally, promotor binding analyses show that the ANAC016 promoter sequence is directly bound by ANAC017, so ANAC016 likely acts downstream of ANAC017 and is directly transcriptionally controlled by ANAC017 in a feed-forward loop during late senescence.

COVID-19 deaths are commoner among care-home residents, but the mortality burden has not been quantified.

Care-home residency was identified via a national primary care registration database linked to mortality data. Life expectancy was estimated using Makeham-Gompertz models to (i) describe yearly life expectancy from November 2015 to October 2020 (ii) compare life expectancy (during 2016-18) between care-home residents and the wider population and (iii) apply care-home life expectancy estimates to COVID-19 death counts to estimate years of life lost (YLL).

Among care-home residents, life expectancy in 2015/16 to 2019/20 ranged from 2.7 to 2.3years for women and 2.3 to 1.8years for men. Age-sex-specific life expectancy in 2016-18 in care-home residents was lower than in the Scottish population (10 and 2.5years in those aged 70 and 90, respectively). Applying care home-specific life expectancies to COVID-19 deaths yield mean YLLs for care-home residents of 2.6 and 2.2 for women and men, respectively. In total YLL care-home residents have lost 3,560years in women and 2,046years in men. Approximately half of deaths and a quarter of YLL attributed to COVID-19 were accounted for by the 5% of over-70s who were care-home residents.

COVID-19 infection has led to the loss of substantial years of life in care-home residents aged 70years and over in Scotland. Prioritising the 5% of older adults who are care-home residents for vaccination is justified not only in terms of total deaths, but also in terms of YLL.

COVID-19 infection has led to the loss of substantial years of life in care-home residents aged 70 years and over in Scotland. Tamoxifen mw Prioritising the 5% of older adults who are care-home residents for vaccination is justified not only in terms of total deaths, but also in terms of YLL.Signaling centers, or organizers, regulate many aspects of embryonic morphogenesis. In the mammalian molar tooth, reiterative signaling in specialized centers called enamel knots (EKs) determines tooth patterning. Preceding the primary EK, transient epithelial thickening appears, the significance of which remains debated. Using tissue confocal fluorescence imaging with laser ablation experiments, we show that this transient thickening is an earlier signaling center, the molar initiation knot (IK), that is required for the progression of tooth development. IK cell dynamics demonstrate the hallmarks of a signaling center cell cycle exit, condensation and eventual silencing through apoptosis. IK initiation and maturation are defined by the juxtaposition of cells with high Wnt activity to Shh-expressing non-proliferating cells, the combination of which drives the growth of the tooth bud, leading to the formation of the primary EK as an independent cell cluster. Overall, the whole development of the tooth, from initiation to patterning, is driven by the iterative use of signaling centers.