Biology subjects

Lewis, L.

Publications and source records attributed to Lewis, L..

4 recordsLinked to original sources

bioRxiv2018

Genetic Determinants of Cortical Structure (Thickness, Surface Area and Volumes) among Disease Free Adults in the CHARGE Consortium

Cortical thickness, surface area and volumes (MRI cortical measures) vary with age and cognitive function, and in neurological and psychiatric diseases. We examined heritability, genetic correlations and genome-wide associations of cortical measures across the whole cortex, and in 34 anatomically predefined regions. Our discovery sample comprised 22,822 individuals from 20 cohorts within the Cohorts for Heart and Aging Research in Genomic Epidemiology (CHARGE) consortium and the United Kingdom Biobank. Significant associations were replicated in the Enhancing Neuroimaging Genetics through Meta-analysis (ENIGMA) consortium, and their biological implications explored using bioinformatic annotation and pathway analyses. We identified genetic heterogeneity between cortical measures and brain regions, and 161 genome-wide significant associations pointing to wnt/{beta}-catenin, TGF-{beta} and sonic hedgehog pathways. There was enrichment for genes involved in anthropometric traits, hindbrain development, vascular and neurodegenerative disease and psychiatric conditions. These data are a rich resource for studies of the biological mechanisms behind cortical development and aging.

genetics↗

bioRxiv2018

Planar cell polarity pathway and development of the human visual cortex

The radial unit hypothesis provides a framework for global (proliferation) and regional (distribution) expansion of the primate cerebral cortex. Using principal component analysis (PCA), we have identified cortical regions with shared variance in their surface area and cortical thickness, respectively, segmented from magnetic resonance images obtained in 23,800 participants. We then carried out meta-analyses of genome-wide association studies of the first two principal components for each phenotype. For surface area (but not cortical thickness), we have detected strong associations between each of the components and single nucleotide polymorphisms in a number of gene loci. The first (global) component was associated mainly with loci on chromosome 17 (9.5e-32 [≤] p [≤] 2.8e-10), including those detected previously as linked with intracranial volume and/or general cognitive function. The second (regional) component captured shared variation in the surface area of the primary and adjacent secondary visual cortices and showed a robust association with polymorphisms in a locus on chromosome 14 containing Disheveled Associated Activator of Morphogenesis 1 (DAAM1; p=2.4e-34). DAAM1 is a key component in the planar-cell-polarity signaling pathway. In follow-up studies, we have focused on the latter finding and established that: (1) DAAM1 is highly expressed between 12th and 22nd post-conception weeks in the human cerebral cortex; (2) genes co-expressed with DAAM1 in the primary visual cortex are enriched in mitochondria-related pathways; and (3) volume of the lateral geniculate nucleus, which projects to regions of the visual cortex staining for cytochrome oxidase (a mitochondrial enzyme), correlates with the surface area of the visual cortex in major-allele homozygotes but not in carriers of the minor allele. Altogether, we speculate that, in concert with thalamocortical input to cortical subplate, DAAM1 enables migration of neurons to cytochrome-oxidase rich regions of the visual cortex, and, in turn, facilitates regional expansion of this set of cortical regions during development.

neuroscience↗

bioRxiv2018

Bioinformatic characterisation of the effector repertoire of the strawberry pathogen Phytophthora cactorum

The oomycete pathogen Phytophthora cactorum causes crown rot, a major disease of cultivated strawberry. We report the draft genome of P. cactorum isolate 10300, cultured from symptomatic Fragaria x ananassa tissue. Our analysis revealed that there are a large number of genes encoding putative secreted effectors in the genome, including nearly 200 RxLR domain containing effectors, 77 Crinklers (CRN) grouped into 38 families and numerous apoplastic effectors, such as phytotoxins (PcF proteins) and necrosis inducing proteins. As in other Phytophthora species, the genomic environment of many RxLR and CRN genes differed from core eukaryotic genes, a hallmark of the two-speed genome. We found genes homologous to known Phytophthora infestans avirulence genes including Avr1, Avr3b, Avr4, Avrblb1 and AvrSmira2 indicating effector sequence conservation between Phytophthora species of Clade 1A and 1C. The reported P. cactorum genome sequence and associated annotations represent a comprehensive resource for avirulence gene discovery in other Phytophthora species from Clade 1 and will facilitate effector informed breeding strategies in other crops.

pathology↗

bioRxiv2018

Specific octopaminergic neurons arbitrate between perseverance and reward in hungry Drosophila

In pursuit of palatable food, hungry animals mobilize significant energy resources and overcome obstacles, exhaustion and fear. Their perseverance depends on metabolic state, internal motivation and the expected benefit. Sustained commitment to a trying task is crucial, however, disengagement from one behavior to engage into another can be essential for optimal adaptation and survival. How neural circuits allow prioritizing perseverance over withdrawal based on the animals need is not understood. Using a single fly spherical treadmill, we show that hungry flies display increasing perseverance to track a food odor in the repeated absence of the predicted food reward. While this perseverance is mediated by a group of dopaminergic neurons, a subset of neurons expressing octopamine, the invertebrate counterpart of noradrenaline, provide reward feedback and counteract dopamine-motivated food seeking. Our data and modeling suggest that two important neuromodulators tally internal and external signals to coordinate motivation-dependent antagonistic behavioral drives: perseverance vs. change of behavior.\n\n\n\nO_FIG O_LINKSMALLFIG WIDTH=200 HEIGHT=87 SRC=\"FIGDIR/small/259119_ufig1.gif\" ALT=\"Figure 1\">\nView larger version (21K):\norg.highwire.dtl.DTLVardef@9833e1org.highwire.dtl.DTLVardef@7616d4org.highwire.dtl.DTLVardef@d4e8bforg.highwire.dtl.DTLVardef@1fc615c_HPS_FORMAT_FIGEXP M_FIG C_FIG HighlightsO_LILack of reward stimulates perseverance, and not quitting.\nC_LIO_LIDopaminergic neurons previously implicated in aversive learning promote perseverance.\nC_LIO_LISugar responsive octopaminergic neurons directly counteract perseverant odor tracking through a downstream inhibitory neuron.\nC_LIO_LIComputational modeling supports a simple neural circuit featuring antagonistic functions for dopamine and octopamine as tallies of expense and gain.\nC_LI

neuroscience↗