Writing for Reading

For some time concern about the writing ability of students has matched the attention given to their reading development. Teachers of all subjects are urged to require their students to write more, and suggestions for helping students improve their writing abound. At the same time we see additional justification for stressing writing; improvement in writing might well lead to improvement in reading

Detecting Remote Sequence Homology in Disordered Proteins: Discovery of Conserved Motifs in the N-Termini of Mononegavirales phosphoproteins

Paramyxovirinae are a large group of viruses that includes measles virus and parainfluenza viruses. The viral Phosphoprotein (P) plays a central role in viral replication. It is composed of a highly variable, disordered N-terminus and a conserved C-terminus. A second viral protein alternatively expressed, the V protein, also contains the N-terminus of P, fused to a zinc finger. We suspected that, despite their high variability, the N-termini of P/V might all be homologous; however, using standard approaches, we could previously identify sequence conservation only in some Paramyxovirinae. We now compared the N-termini using sensitive sequence similarity search programs, able to detect residual similarities unnoticeable by conventional approaches. We discovered that all Paramyxovirinae share a short sequence motif in their first 40 amino acids, which we called soyuz1. Despite its short length (11–16aa), several arguments allow us to conclude that soyuz1 probably evolved by homologous descent, unlike linear motifs. Conservation across such evolutionary distances suggests that soyuz1 plays a crucial role and experimental data suggest that it binds the viral nucleoprotein to prevent its illegitimate self-assembly. In some Paramyxovirinae, the N-terminus of P/V contains a second motif, soyuz2, which might play a role in blocking interferon signaling. Finally, we discovered that the P of related Mononegavirales contain similarly overlooked motifs in their N-termini, and that their C-termini share a previously unnoticed structural similarity suggesting a common origin. Our results suggest several testable hypotheses regarding the replication of Mononegavirales and suggest that disordered regions with little overall sequence similarity, common in viral and eukaryotic proteins, might contain currently overlooked motifs (intermediate in length between linear motifs and disordered domains) that could be detected simply by comparing orthologous proteins

Four erroneous beliefs thwarting more trustworthy research.

A range of problems currently undermines public trust in biomedical research. We discuss four erroneous beliefs that may prevent the biomedical research community from recognizing the need to focus on deserving this trust, and thus which act as powerful barriers to necessary improvements in the research process

Phase Ib study of the combination of pexidartinib (PLX3397), a CSF-1R inhibitor, and paclitaxel in patients with advanced solid tumors.

Purpose:To evaluate the safety, recommended phase II dose (RP2D) and efficacy of pexidartinib, a colony stimulating factor receptor 1 (CSF-1R) inhibitor, in combination with weekly paclitaxel in patients with advanced solid tumors. Patients and Methods:In part 1 of this phase Ib study, 24 patients with advanced solid tumors received escalating doses of pexidartinib with weekly paclitaxel (80 mg/m2). Pexidartinib was administered at 600 mg/day in cohort 1. For subsequent cohorts, the dose was increased by ⩽50% using a standard 3+3 design. In part 2, 30 patients with metastatic solid tumors were enrolled to examine safety, tolerability and efficacy of the RP2D. Pharmacokinetics and biomarkers were also assessed. Results:A total of 51 patients reported ≥1 adverse event(s) (AEs) that were at least possibly related to either study drug. Grade 3-4 AEs, including anemia (26%), neutropenia (22%), lymphopenia (19%), fatigue (15%), and hypertension (11%), were recorded in 38 patients (70%). In part 1, no maximum tolerated dose was achieved and 1600 mg/day was determined to be the RP2D. Of 38 patients evaluable for efficacy, 1 (3%) had complete response, 5 (13%) partial response, 13 (34%) stable disease, and 17 (45%) progressive disease. No drug-drug interactions were found. Plasma CSF-1 levels increased 1.6- to 53-fold, and CD14dim/CD16+ monocyte levels decreased by 57-100%. Conclusions:The combination of pexidartinib and paclitaxel was generally well tolerated. RP2D for pexidartinib was 1600 mg/day. Pexidartinib blocked CSF-1R signaling, indicating potential for mitigating macrophage tumor infiltration

Ecological and genetic effects of introduced species on their native competitors

Species introductions to new habitats can cause a decline in the population size of competing native species and consequently also in their genetic diversity. We are interested in why these adverse effects are weak in some cases whereas in others the native species declines to the point of extinction. While the introduction rate and the growth rate of the introduced species in the new environment clearly have a positive relationship with invasion success and impact, the influence of competition is poorly understood. Here, we investigate how the intensity of interspecific competition influences the persistence time of a native species in the face of repeated and ongoing introductions of the nonnative species. We analyze two stochastic models: a model for the population dynamics of both species and a model that additionally includes the population genetics of the native species at a locus involved in its adaptation to a changing environment. Counterintuitively, both models predict that the persistence time of the native species is lowest for an intermediate intensity of competition. This phenomenon results from the opposing effects of competition at different stages of the invasion process: With increasing competition intensity more introduction events are needed until a new species can establish, but increasing competition also speeds up the exclusion of the native species by an established nonnative competitor. By comparing the ecological and the eco-genetic model, we detect and quantify a synergistic feedback between ecological and genetic effects.Comment: version accepted at Theoretical Population Biolog

Overlapping genes and the proteins they encode differ significantly in their sequence composition from non-overlapping genes.

Overlapping genes represent a fascinating evolutionary puzzle, since they encode two functionally unrelated proteins from the same DNA sequence. They originate by a mechanism of overprinting, in which point mutations in an existing frame allow the expression (the "birth") of a completely new protein from a second frame. In viruses, in which overlapping genes are abundant, these new proteins often play a critical role in infection, yet they are frequently overlooked during genome annotation. This results in erroneous interpretation of mutational studies and in a significant waste of resources. Therefore, overlapping genes need to be correctly detected, especially since they are now thought to be abundant also in eukaryotes. Developing better detection methods and conducting systematic evolutionary studies require a large, reliable benchmark dataset of known cases. We thus assembled a high-quality dataset of 80 viral overlapping genes whose expression is experimentally proven. Many of them were not present in databases. We found that overall, overlapping genes differ significantly from non-overlapping genes in their nucleotide and amino acid composition. In particular, the proteins they encode are enriched in high-degeneracy amino acids and depleted in low-degeneracy ones, which may alleviate the evolutionary constraints acting on overlapping genes. Principal component analysis revealed that the vast majority of overlapping genes follow a similar composition bias, despite their heterogeneity in length and function. Six proven mammalian overlapping genes also followed this bias. We propose that this apparently near-universal composition bias may either favour the birth of overlapping genes, or/and result from selection pressure acting on them

2019-2020 Philharmonia No. 4

Concert Date & Time: February 22, 2020 at 7:30 pm and February 23, 2020 at 4:00 pm Program Short Ride in a Fast Machine / John Adams Lincoln Portrait / Aaron Copland Jon Robertson, narrator Symphony No. 9 in D minor, Op. 125 / Ludwig van Beethoven Sherezade Panthaki, soprano Rebecca Robinson, mezzo-soprano Robert Stahley, tenor Adrian Smith, baritone The Master Chorale of South Florida Brett Karlin, artistic directorhttps://spiral.lynn.edu/conservatory_philharmonia/1150/thumbnail.jp

Asymptotic behaviour of zeros of exceptional Jacobi and Laguerre polynomials

The location and asymptotic behaviour for large n of the zeros of exceptional Jacobi and Laguerre polynomials are discussed. The zeros of exceptional polynomials fall into two classes: the regular zeros, which lie in the interval of orthogonality and the exceptional zeros, which lie outside that interval. We show that the regular zeros have two interlacing properties: one is the natural interlacing between consecutive polynomials as a consequence of their Sturm-Liouville character, while the other one shows interlacing between the zeros of exceptional and classical polynomials. A generalization of the classical Heine-Mehler formula is provided for the exceptional polynomials, which allows to derive the asymptotic behaviour of their regular zeros. We also describe the location and the asymptotic behaviour of the exceptional zeros, which converge for large n to fixed values.Comment: 19 pages, 3 figures, typed in AMS-LaTe

Carbonate deposition and benthicδ13C in the subarctic Pacific: implications for changes of the oceanic carbonate system during the past 750,000 years

Carbonate deposition at two core sites in the subarctic Pacific (48°N, 133°W; 2.9 km and 3.7 km water depth) follows the standard Pacific carbonate cycles, with glacial values being increased over interglacial values. Benthicδ13C follows the global trend; that is, glacial values are more negative than interglacial values. Comparison with the benthicδ13C record of North Atlantic DSDP Site 552 (56°N, 23°W; 2.3 km water depth) shows the North Pacific records to be nearly in phase with and continuously more negative relative to the North Atlantic record. This suggests that concentrations of∑CO2(org) were permanently higher in the North Pacific than in the North Atlantic during the past 750,000 years conceivably supporting the hypothesis that there was no deep-water forming in the late Pleistocene North Pacific. Whereas one would expect that the North Pacific deep waters were continuously more corrosive to carbonates than deep waters in the North Atlantic, carbonate deposition at the deep North Pacific core sites is enhanced during glacial periods, and occasionally higher than at shallow North Atlantic Site 552 even though Site 552 was probably above lysocline-depth during most of the late Pleistocene. This apparent paradox can be resolved only by invoking an increase in alkalinity in the glacial North Pacific which would have increased the degree of carbonate ion saturation and thereby improved the state of carbonate preservation

Distinguishing Microbial Genome Fragments Based on Their Composition: Evolutionary and Comparative Genomic Perspectives

It is well known that patterns of nucleotide composition vary within and among genomes, although the reasons why these variations exist are not completely understood. Between-genome compositional variation has been exploited to assign environmental shotgun sequences to their most likely originating genomes, whereas within-genome variation has been used to identify recently acquired genetic material such as pathogenicity islands. Recent sequence assignment techniques have achieved high levels of accuracy on artificial data sets, but the relative difficulty of distinguishing lineages with varying degrees of relatedness, and different types of genomic sequence, has not been examined in depth. We investigated the compositional differences in a set of 774 sequenced microbial genomes, finding rapid divergence among closely related genomes, but also convergence of compositional patterns among genomes with similar habitats. Support vector machines were then used to distinguish all pairs of genomes based on genome fragments 500 nucleotides in length. The nearly 300,000 accuracy scores obtained from these trials were used to construct general models of distinguishability versus taxonomic and compositional indices of genomic divergence. Unusual genome pairs were evident from their large residuals relative to the fitted model, and we identified several factors including genome reduction, putative lateral genetic transfer, and habitat convergence that influence the distinguishability of genomes. The positional, compositional, and functional context of a fragment within a genome has a strong influence on its likelihood of correct classification, but in a way that depends on the taxonomic and ecological similarity of the comparator genome