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Biology subjects

Bayer, P.

Publications and source records attributed to Bayer, P..

7 recordsLinked to original sources

Capturing the missing gene content of elite wheat by analysis of wheat landraces

There is a need to breed superior wheat cultivars to meet increasing global food demand. However, modern cultivars have undergone a substantial loss of genetic diversity due to intensive breeding. A pool of genetic diversity remains untapped in wheat landraces, and pangenomics can help identify genes of potential agronomic importance in these old lines that can be applied to accelerate wheat improvement. Here, we have constructed the largest wheat pangenome to date, representing 1,061 diverse individuals (827 landraces and 234 modern cultivars) from 47 countries across six continents. We identified 10,426 predicted gene models specific to landraces that are enriched for functions associated with disease resistance, abiotic stress adaptation, and symbiosis. Our results reveal that landraces harbour an extensive repertoire of genes that are absent from modern wheat cultivars and provide a foundational resource for the systematic reintroduction of adaptive variation to enhance wheat resilience and sustainability in the face of climate change.

plant biology↗

Blueberry and cranberry pangenomes as a resource for future genetic studies and breeding efforts

Domestication of cranberry and blueberry began in the United States in the early 1800s and 1900s, respectively, and in part owing to their flavors and health-promoting benefits are now cultivated and consumed worldwide. The industry continues to face a wide variety of production challenges (e.g. disease pressures) as well as a demand for higher-yielding cultivars with improved fruit quality characteristics. Unfortunately, molecular tools to help guide breeding efforts for these species have been relatively limited compared with those for other high-value crops. Here, we describe the construction and analysis of the first pangenome for both blueberry and cranberry. Our analysis of these pangenomes revealed both crops exhibit great genetic diversity, including the presence-absence variation of 48.4% genes in highbush blueberry and 47.0% genes in cranberry. Auxiliary genes, those not shared by all cultivars, are significantly enriched with molecular functions associated with disease resistance and the biosynthesis of specialized metabolites, including compounds previously associated with improving fruit quality traits. The discovery of thousands of genes, not present in the previous reference genomes for blueberry and cranberry, will serve as the basis of future research and as potential targets for future breeding efforts. The pangenome, as a multiple-sequence alignment, as well as individual annotated genomes, are publicly available for analysis on the Genome Database for Vaccinium - a curated and integrated web-based relational database. Lastly, the core-gene predictions from the pangenomes will serve useful to develop a community genotyping platform to guide future molecular breeding efforts across the family.

genomics↗

Continued dysfunction of capillary pericytes promotes no-reflow after experimental stroke in vivo

Incomplete reperfusion of the microvasculature ("no-reflow") after ischemic stroke damages salvageable brain tissue. Previous ex-vivo studies suggest pericytes are vulnerable to ischemia and may exacerbate no-reflow, but the viability of pericytes and their association with no-reflow remains underexplored in vivo. Using longitudinal in vivo 2-photon single-cell imaging over seven days we show 87% of pericytes constrict during cerebral ischemia, remain constricted post-reperfusion and 50% of the pericyte population are acutely damaged. Moreover, we reveal ischemic pericytes are fundamentally implicated in capillary no-reflow by limiting and arresting blood flow within the first 24 hours post-stroke. Despite sustaining acute membrane damage, we observe up to 80% of cortical pericytes survive ischemia, upregulate unique transcriptomic profiles and replicate. Finally, we demonstrate delayed recovery of capillary diameter by ischemic pericytes after reperfusion predicts vessel reconstriction in the sub-acute phase of stroke. Cumulatively, these findings demonstrate surviving cortical pericytes remain both viable and promising therapeutic targets to counteract no-reflow after ischemic stroke.

neuroscience↗

Games and the treatment convexity of cancer

Evolutionary game theory has been highly valuable in studying frequency-dependent selection and growth between competing cancer phenotypes. We study the connection between the type of competition as defined by properties of the game, and the convexity of the treatment response function. Convexity is predictive of differences in the tumors response to treatments with identical cumulative doses delivered with different variances. We rely on a classification of 2 x 2 games based on the signs of dilemma strengths, containing information about the kind of selection through the games equilibrium structure. With the disease starting in one game class, we map the type of effects treatment may have on the game depending on dosage and the implications of treatment convexity. Treatment response is a linear function of dose if the game is a prisoners dilemma, coordination, or harmony game and does not change game class, but may be convex or concave for anti-coordination games. If the game changes class, there is a rich variety in response types including convex-concave and concave-convex responses for transitions involving anti-coordination games, response discontinuity in case of a transition out of coordination games, and hysteresis in case of a transition through coordination games.

cancer biology↗

Brassica napus genes Rlm4 and Rlm7, conferring resistance to Leptosphaeria maculans, are alleles of the Rlm9 wall-associated kinase-like resistance locus

Brassica napus (canola/rapeseed) race specific resistance genes against blackleg disease, caused by the ascomycete fungus Leptosphaeria maculans, have been commonly used in canola breeding. To date; LepR3, Rlm2 and Rlm9 R genes against L. maculans have been cloned from B. napus. LepR3 and Rlm2 are Receptor Like Proteins (RLP) and the recently reported Rlm9 is a Wall Associated Kinase-Like (WAKL) protein. Rlm9 located on chromosome A07 is closely linked with Rlm3, Rlm4, RLm7 genes. Recognition of AvrLm5-9 and AvrLm3 by their corresponding Rlm9 and Rlm3 proteins is masked in the presence of AvrLm4-7. Here we report cloning of Rlm4 and Rlm7 by generating genome sequence of the doubled haploid (DH) B. napus cv Topas DH16516 introgression lines Topas-Rlm4 and Topas-Rlm7. Candidate Rlm4 and Rlm7 genes were identified form the genome sequence and gene structures were determined by mapping RNA-sequence reads, generated from infected cotyledon tissues, to the genome of Topas-Rlm4 and Topas-Rlm7. Rlm4 and Rlm7 genomic constructs with their native promoters were transferred into the blackleg susceptible B. napus cv Westar N-o-1. Complementation of resistance response in the transgenic Westar:Rlm4 and Westar:Rlm7 that were inoculated with L. maculans transgenic isolates 2367:AvrRlm4-7 or 2367:AvrLm7 confirmed the function of Rlm4 and Rlm7 genes. Wild type L. maculans isolate 2367 that does not contain AvrLm4-7 or AvrLm7, and transgenic 2367:AvrLm3 and 2367:AvrLm5-9 did not induce resistance proving the specificity of Rlm4 and Rlm7 response. Rlm4 and Rlm7 alleles are also allelic to Rlm9. Rlm4 and Rlm7 genes encode WAKL proteins. Comparison of highly homologous sequences of Rlm4 and Rlm7 with each other and with the sequence of additional alleles, using whole genome sequencing of additional 128 lines, identified a limited number of point mutation located within the predicted extracellular receptor domains.

plant biology↗

Coordination games in cancer

We propose a model of cancer initiation and progression where tumor growth is modulated by an evolutionary coordination game. Evolutionary games of cancer are widely used to model frequency-dependent cell interactions with the most studied games being the Prisoners Dilemma and public goods games. Coordination games, by their more obscure and less evocative nature, are left understudied, despite the fact that, as we argue, they offer great potential in understanding and treating cancer. In this paper we present the conditions under which coordination games between cancer cells evolve, we propose aspects of cancer that can be modeled as results of coordination games, and explore the ways through which coordination games of cancer can be exploited for therapy.

cancer biology↗

A Markov chain model of cancer treatment

This paper develops and analyzes a Markov chain model for the treatment of cancer. Cancer therapy is modeled as the patients Markov Decision Problem, with the objective of maximizing the patients discounted expected quality of life years. Patients choose the number of treatment rounds they wish to administer based on the progression of the disease as well as their own preferences. We obtain a powerful analytic decision tool by which patients may select their preferred treatment strategy. In a second model patients may make choices on the timing of treatment rounds as well. By delaying a round of therapy the patient forgoes the gains of therapy for a time in order to delay its side effects. We obtain an analytic tool that allows numerical approximations of the optimal times of delay.

cancer biology↗