Environmental fluctuations accelerate molecular evolution of thermal tolerance in a marine diatom

This is the final version of the article. Available from Springer Nature via the DOI in this recordThe publisher correction to this article is in ORE at: http://hdl.handle.net/10871/34487Diatoms contribute roughly 20% of global primary production, but the factors determining their ability to adapt to global warming are unknown. Here we quantify the capacity for adaptation to warming in the marine diatom Thalassiosira pseudonana. We find that evolutionary rescue under severe (32 °C) warming is slow, but adaptation to more realistic scenarios where temperature increases are moderate (26 °C) or fluctuate between benign and severe conditions is rapid and linked to phenotypic changes in metabolic traits and elemental composition. Whole-genome re-sequencing identifies genetic divergence among populations selected in the different warming regimes and between the evolved and ancestral lineages. Consistent with the phenotypic changes, the most rapidly evolving genes are associated with transcriptional regulation, cellular responses to oxidative stress and redox homeostasis. These results demonstrate that the evolution of thermal tolerance in marine diatoms can be rapid, particularly in fluctuating environments, and is underpinned by major genomic and phenotypic change.This study was funded by a Leverhulme Trust research grant (RPG-2013-335). Whole genome re-sequencing was carried out at Exeter Sequencing Service and Computational core facilities at the University of Exeter, where Dr. Karen Moore, Dr. Audrey Farbos, Paul O’Neill, and Dr. Konrad Paszkiewicz lead the handling of the samples. Exeter Squencing Services are supported by Medical Research Council Clinical Infrastructure award (MR/M008924/1), Wellcome Trust Institutional Strategic Support Fund (WT097835MF), Wellcome Trust Multi User Equipment Award (WT101650MA), and BBSRC LOLA award (BB/K003240/1)

Publisher Correction: Environmental fluctuations accelerate molecular evolution of thermal tolerance in a marine diatom

The article for which this is the publisher correction is in ORE at: http://hdl.handle.net/10871/32652The PDF version of this Article was updated shortly after publication following an error which resulted in the Φ symbol being omitted from the left hand side of equation 8. The HTML version was correct from the time of publication

Drawing Planar Graphs with Few Geometric Primitives

We define the \emph{visual complexity} of a plane graph drawing to be the number of basic geometric objects needed to represent all its edges. In particular, one object may represent multiple edges (e.g., one needs only one line segment to draw a path with an arbitrary number of edges). Let $n$ denote the number of vertices of a graph. We show that trees can be drawn with $3n/4$ straight-line segments on a polynomial grid, and with $n/2$ straight-line segments on a quasi-polynomial grid. Further, we present an algorithm for drawing planar 3-trees with $(8n-17)/3$ segments on an $O(n)\times O(n^2)$ grid. This algorithm can also be used with a small modification to draw maximal outerplanar graphs with $3n/2$ edges on an $O(n)\times O(n^2)$ grid. We also study the problem of drawing maximal planar graphs with circular arcs and provide an algorithm to draw such graphs using only $(5n - 11)/3$ arcs. This is significantly smaller than the lower bound of $2n$ for line segments for a nontrivial graph class.Comment: Appeared at Proc. 43rd International Workshop on Graph-Theoretic Concepts in Computer Science (WG 2017

Interleukin-12/23 deficiency differentially affects pathology in male and female Alzheimer's disease-like mice

Pathological aggregation of amyloid-β (Aβ) is a main hallmark of Alzheimer's disease (AD). Recent genetic association studies have linked innate immune system actions to AD development, and current evidence suggests profound gender differences in AD pathogenesis. Here, we characterise gender-specific pathologies in the APP23 AD-like mouse model and find that female mice show stronger amyloidosis and astrogliosis compared with male mice. We tested the gender-specific effect of lack of IL12p40, the shared subunit of interleukin (IL)-12 and IL-23, that we previously reported to ameliorate pathology in APPPS1 mice. IL12p40 deficiency gender specifically reduces A plaque burden in male APP23 mice, while in female mice, a significant reduction in soluble Aβ without changes in Aβ plaque burden is seen. Similarly, plasma and brain cytokine levels are altered differently in female versus male APP23 mice lacking IL12p40, while glial properties are unchanged. These data corroborate the therapeutic potential of targeting IL-12/IL-23 signalling in AD, but also highlight the importance of gender considerations when studying the role of the immune system and AD

Interleukin-12/23 deficiency differentially affects pathology in male and female Alzheimer's disease-like mice

Pathological aggregation of amyloid-β (Aβ) is a main hallmark of Alzheimer's disease (AD). Recent genetic association studies have linked innate immune system actions to AD development, and current evidence suggests profound gender differences in AD pathogenesis. Here, we characterise gender-specific pathologies in the APP23 AD-like mouse model and find that female mice show stronger amyloidosis and astrogliosis compared with male mice. We tested the gender-specific effect of lack of IL12p40, the shared subunit of interleukin (IL)-12 and IL-23, that we previously reported to ameliorate pathology in APPPS1 mice. IL12p40 deficiency gender specifically reduces A plaque burden in male APP23 mice, while in female mice, a significant reduction in soluble Aβ without changes in Aβ plaque burden is seen. Similarly, plasma and brain cytokine levels are altered differently in female versus male APP23 mice lacking IL12p40, while glial properties are unchanged. These data corroborate the therapeutic potential of targeting IL-12/IL-23 signalling in AD, but also highlight the importance of gender considerations when studying the role of the immune system and AD

Administration of misoprostol by trained traditional birth attendants to prevent postpartum haemorrhage in homebirths in Pakistan: a randomised placebo-controlled trial

Gynuit

Planar projections of graphs

We introduce and study a new graph representation where vertices are embedded in three or more dimensions, and in which the edges are drawn on the projections onto the axis-parallel planes. We show that the complete graph on $n$ vertices has a representation in $\lceil \sqrt{n/2}+1 \rceil$ planes. In 3 dimensions, we show that there exist graphs with $6n-15$ edges that can be projected onto two orthogonal planes, and that this is best possible. Finally, we obtain bounds in terms of parameters such as geometric thickness and linear arboricity. Using such a bound, we show that every graph of maximum degree 5 has a plane-projectable representation in 3 dimensions.Comment: Accepted at CALDAM 202

Two redundant ubiquitin-dependent pathways of BRCA1 localization to DNA damage sites

The tumor suppressor BRCA1 accumulates at sites of DNA damage in a ubiquitin-dependent manner. In this work, we revisit the role of RAP80 in promoting BRCA1 recruitment to damaged chromatin. We find that RAP80 acts redundantly with the BRCA1 RING domain to promote BRCA1 recruitment to DNA damage sites. We show that that RNF8 E3 ligase acts upstream of both the RAP80- and RING-dependent activities, whereas RNF168 acts uniquely upstream of the RING domain. BRCA1 RING mutations that do not impact BARD1 interaction, such as the E2 binding-deficient I26A mutation, render BRCA1 unable to accumulate at DNA damage sites in the absence of RAP80. Cells that combine BRCA1 I26A and mutations that disable the RAP80-BRCA1 interaction are hypersensitive to PARP inhibition and are unable to form RAD51 foci. Our results suggest that in the absence of RAP80, the BRCA1 E3 ligase activity is necessary for recognition of histone H2A Lys13/Lys15 ubiquitylation by BARD1, although we cannot rule out the possibility that the BRCA1 RING facilitates ubiquitylated nucleosome recognition in other ways.Genome Instability and Cance