Extreme Pyroconvective Updrafts During a Megafire

Airborne cloud radar reveals extreme wildfire updrafts (~60 m s−1) and downdrafts (~30 m s−1) rivaling those in supercell thunderstorms. These extreme vertical velocities occur through a 3-km-deep layer and below the base of a developing pyrocumulonimbus (pyroCb) cloud, which extends to the tropopause at 12 km. In situ aircraft sampling shows updrafts are linked to large temperature and moisture excesses but remain subsaturated at flight level (i.e., below cloud base). Parcel estimates using the in situ data help explain how these “hot-moist” updrafts trigger the overlying pyroCb. The extreme vertical motions observed also pose a previously undocumented aviation hazard

Accurate design of translational output by a neural network model of ribosome distribution

Synonymous codon choice can have dramatic effects on ribosome speed and protein expression. Ribosome profiling experiments have underscored that ribosomes do not move uniformly along mRNAs. Here, we have modeled this variation in translation elongation by using a feed-forward neural network to predict the ribosome density at each codon as a function of its sequence neighborhood. Our approach revealed sequence features affecting translation elongation and characterized large technical biases in ribosome profiling. We applied our model to design synonymous variants of a fluorescent protein spanning the range of translation speeds predicted with our model. Levels of the fluorescent protein in budding yeast closely tracked the predicted translation speeds across their full range. We therefore demonstrate that our model captures information determining translation dynamics in vivo; that this information can be harnessed to design coding sequences; and that control of translation elongation alone is sufficient to produce large quantitative differences in protein output

In situ microphysics observations of intense pyroconvection from a large wildfire

This study characterizes the size and shape distributions of 10 µm to 6 mm diameter particles observed during six penetrations of wildfire-induced pyroconvection near Boise, Idaho, USA, by a research aircraft over the period 29–30 August 2016. In situ measurements by the aircraft include winds, atmospheric state, and bulk water content and particle concentration, size, and shape. These observations are complemented by data from airborne and ground-based radars. One of the penetrations is through a subsaturated smoke–ash plume with negligible cloud liquid water content that is characterized by an updraft of almost 36 m s−1. The size distribution of number concentration is very similar to that documented previously for a smoke plume from a prescribed fire, and particle shapes exhibit qualitative and quantitative attributes comparable to ash particles created in a burn chamber. Particles sampled during this penetration are most likely pyrometeors composed of ash. Pyrocumulus clouds are probed in the other penetrations where values of relative humidity and cloud liquid water content are larger, but updrafts are weaker. Compared to the smoke-plume penetration, size distributions are mostly characterized by larger concentration, and particle shapes exhibit a higher degree of circular symmetry. Particle composition in these pyrocumulus penetrations is most likely a combination of hydrometeors (ice particles) and pyrometeors (ash).</p

Raising children with high self-esteem (but not narcissism)

With the rise of individualism since the 1960s, Western parents have become increasingly concerned with raising children’s self-esteem. This is understandable, given the benefits of self-esteem for children’s psychological health. However, parents’ well-intentioned attempts to raise self-esteem, such as inflated praise, may inadvertently breed narcissism. How, then, can parents raise self-esteem without breeding narcissism? Here, we propose a tripartite model of self-regard, which holds that the development of self-esteem without narcissism can be cultivated through realistic feedback (rather than inflated praise), focus on growth (rather than on outperforming others), and unconditional regard (rather than regard that is conditional). We review evidence in support of these practices and outline promising research directions. The tripartite model integrates existing research, stimulates theory development, and identifies leverage points for intervention concurrently to raise self-esteem and curtail narcissism from a young age

Accurate design of translational output by a neural network model of ribosome distribution

Synonymous codon choice can have dramatic effects on ribosome speed and protein expression. Ribosome profiling experiments have underscored that ribosomes do not move uniformly along mRNAs. Here, we have modeled this variation in translation elongation by using a feed-forward neural network to predict the ribosome density at each codon as a function of its sequence neighborhood. Our approach revealed sequence features affecting translation elongation and characterized large technical biases in ribosome profiling. We applied our model to design synonymous variants of a fluorescent protein spanning the range of translation speeds predicted with our model. Levels of the fluorescent protein in budding yeast closely tracked the predicted translation speeds across their full range. We therefore demonstrate that our model captures information determining translation dynamics in vivo; that this information can be harnessed to design coding sequences; and that control of translation elongation alone is sufficient to produce large quantitative differences in protein output

Genome-Wide Identification of Alternative Splice Forms Down-Regulated by Nonsense-Mediated mRNA Decay in Drosophila

Alternative mRNA splicing adds a layer of regulation to the expression of thousands of genes in Drosophila melanogaster. Not all alternative splicing results in functional protein; it can also yield mRNA isoforms with premature stop codons that are degraded by the nonsense-mediated mRNA decay (NMD) pathway. This coupling of alternative splicing and NMD provides a mechanism for gene regulation that is highly conserved in mammals. NMD is also active in Drosophila, but its effect on the repertoire of alternative splice forms has been unknown, as has the mechanism by which it recognizes targets. Here, we have employed a custom splicing-sensitive microarray to globally measure the effect of alternative mRNA processing and NMD on Drosophila gene expression. We have developed a new algorithm to infer the expression change of each mRNA isoform of a gene based on the microarray measurements. This method is of general utility for interpreting splicing-sensitive microarrays and high-throughput sequence data. Using this approach, we have identified a high-confidence set of 45 genes where NMD has a differential effect on distinct alternative isoforms, including numerous RNA–binding and ribosomal proteins. Coupled alternative splicing and NMD decrease expression of these genes, which may in turn have a downstream effect on expression of other genes. The NMD–affected genes are enriched for roles in translation and mitosis, perhaps underlying the previously observed role of NMD factors in cell cycle progression. Our results have general implications for understanding the NMD mechanism in fly. Most notably, we found that the NMD–target mRNAs had significantly longer 3′ untranslated regions (UTRs) than the nontarget isoforms of the same genes, supporting a role for 3′ UTR length in the recognition of NMD targets in fly

Large introns in relation to alternative splicing and gene evolution: a case study of Drosophila bruno-3

Background: Alternative splicing (AS) of maturing mRNA can generate structurally and functionally distinct transcripts from the same gene. Recent bioinformatic analyses of available genome databases inferred a positive correlation between intron length and AS. To study the interplay between intron length and AS empirically and in more detail, we analyzed the diversity of alternatively spliced transcripts (ASTs) in the Drosophila RNA-binding Bruno-3 (Bru-3) gene. This gene was known to encode thirteen exons separated by introns of diverse sizes, ranging from 71 to 41,973 nucleotides in D. melanogaster. Although Bru-3's structure is expected to be conducive to AS, only two ASTs of this gene were previously described. Results: Cloning of RT-PCR products of the entire ORF from four species representing three diverged Drosophila lineages provided an evolutionary perspective, high sensitivity, and long-range contiguity of splice choices currently unattainable by high-throughput methods. Consequently, we identified three new exons, a new exon fragment and thirty-three previously unknown ASTs of Bru-3. All exon-skipping events in the gene were mapped to the exons surrounded by introns of at least 800 nucleotides, whereas exons split by introns of less than 250 nucleotides were always spliced contiguously in mRNA. Cases of exon loss and creation during Bru-3 evolution in Drosophila were also localized within large introns. Notably, we identified a true de novo exon gain: exon 8 was created along the lineage of the obscura group from intronic sequence between cryptic splice sites conserved among all Drosophila species surveyed. Exon 8 was included in mature mRNA by the species representing all the major branches of the obscura group. To our knowledge, the origin of exon 8 is the first documented case of exonization of intronic sequence outside vertebrates. Conclusion: We found that large introns can promote AS via exon-skipping and exon turnover during evolution likely due to frequent errors in their removal from maturing mRNA. Large introns could be a reservoir of genetic diversity, because they have a greater number of mutable sites than short introns. Taken together, gene structure can constrain and/or promote gene evolution

Innovation in technology-enhanced assessment in the UK and the USA: future scenarios and critical considerations

This paper uses methods derived from the field of futures studies to explore the future of technology-enhanced assessment. Drawing on interviews and consultation activities with experts, the paper aims to discuss the conditions that can impede or foster ‘innovation’ in assessment and education more broadly. Through a review of relevant research, the paper suggests an interpretive model of the factors sustaining the conservatism of educational assessment: the utilitarian view of education, dominant beliefs about academic excellence, and market or quasi-market dynamics. In the central section of the paper, three scenarios of innovation in assessment are described, developed through an iterative process involving researchers, representatives from the e-assessment industry, and experts from British awarding organisations. In the final section, a critical discussion draws attention to the implications that data pervasiveness and computer-generated predictive models may have for the future of education

The fitness cost of mis-splicing is the main determinant of alternative splicing patterns

Background Most eukaryotic genes are subject to alternative splicing (AS), which may contribute to the production of protein variants or to the regulation of gene expression via nonsense-mediated messenger RNA (mRNA) decay (NMD). However, a fraction of splice variants might correspond to spurious transcripts and the question of the relative proportion of splicing errors to functional splice variants remains highly debated. Results We propose a test to quantify the fraction of AS events corresponding to errors. This test is based on the fact that the fitness cost of splicing errors increases with the number of introns in a gene and with expression level. We analyzed the transcriptome of the intron-rich eukaryote Paramecium tetraurelia. We show that in both normal and in NMD-deficient cells, AS rates strongly decrease with increasing expression level and with increasing number of introns. This relationship is observed for AS events that are detectable by NMD as well as for those that are not, which invalidates the hypothesis of a link with the regulation of gene expression. Our results show that in genes with a median expression level, 92–98% of observed splice variants correspond to errors. We observed the same patterns in human transcriptomes and we further show that AS rates correlate with the fitness cost of splicing errors. Conclusions These observations indicate that genes under weaker selective pressure accumulate more maladaptive substitutions and are more prone to splicing errors. Thus, to a large extent, patterns of gene expression variants simply reflect the balance between selection, mutation, and drift