Biology subjects

Taylor, M.

Publications and source records attributed to Taylor, M..

5 recordsLinked to original sources

bioRxiv2018

A cellular automaton for modeling non-trivial biomembrane ruptures

A novel cellular automaton (CA) for simulating biological membrane rupture is proposed. Constructed via simple rules governing deformation, tension, and fracture, the CA incorporates ideas from standard percolation models and bond-based fracture methods. The model is demonstrated by comparing simulations with experimental results of a double bilayer lipid membrane expanding on a solid substrate. Results indicate that the CA can capture non-trivial rupture morphologies such as floral patterns and the saltatory dynamics of fractal avalanches observed in experiments. Moreover, the CA provides insight into the poorly understood role of inter-layer adhesion, supporting the hypothesis that the density of adhesion sites governs rupture morphology.

bioengineering↗

bioRxiv2018

Phylogenetic factorization of mammalian viruses complements trait-based analyses and guides surveillance efforts

Predicting which novel microorganisms may spill over from animals to humans has become a major priority in infectious disease biology. However, there are few tools to help assess the zoonotic potential of the enormous number of potential pathogens, the majority of which are undiscovered or unclassified and may be unlikely to infect or cause disease in humans. We adapt a new biological machine learning technique - phylofactorization - to partition viruses into clades based on their non-human host range and whether or not there exist evidence they have infected humans. Our cladistic analyses identify clades of viruses with common within-clade patterns - unusually high or low propensity for spillover. Phylofactorization by spillover yields many clades of viruses containing few to no representatives that have spilled over to humans, including the families Papillomaviridae and Herpesviridae, and the genus Parvovirus. Removal of these non-zoonotic clades from previous trait-based analyses changed the relative significance of traits determining spillover due to strong associations of traits with non-zoonotic clades. Phylofactorization by host breadth yielded clades with unusually high host breadth, including the family Togaviridae. We identify putative life-history traits differentiating clades host breadth and propensities for zoonosis, and discuss how these results can prioritize sequencing-based surveillance of emerging infectious diseases.

epidemiology↗

bioRxiv2018

Idiosyncratic, retinotopic bias in face identification modulated by familiarity

The perception of gender and age of unfamiliar faces is reported to vary idiosyncratically across retinal locations such that, for example, the same androgynous face may appear to be male at one location but female at another. Here we test spatial heterogeneity for the recognition of the identity of personally familiar faces in human participants. We found idiosyncratic biases that were stable within participants and that varied more across locations for low as compared to high familiar faces. These data suggest that like face gender and age, face identity is processed, in part, by independent populations of neurons monitoring restricted spatial regions and that the recognition responses vary for the same face across these different locations. Moreover, repeated and varied social interactions appear to lead to adjustments of these independent face recognition neurons so that the same familiar face is eventually more likely to elicit the same recognition response across widely separated visual field locations. We provide a mechanistic account of this reduced retinotopic bias based on computational simulations.\n\nSignificance statementIn this work we tested spatial heterogeneity for the recognition of personally familiar faces. We found retinotopic biases that varied more across locations for low as compared to highly familiar faces. The retinotopic biases were idiosyncratic and stable within participants. Our data suggest that, like face gender and age, face identity is processed by independent populations of neurons monitoring restricted spatial regions and that recognition may vary for the same face at these different locations. Unlike previous findings, our data and computational simulation address the effects of learning and show how increased familiarity modifies the representation of face identity in face-responsive cortical areas. This new perspective has broader implications for understanding how learning optimizes visual processes for socially salient stimuli.

neuroscience↗

bioRxiv2017

Impaired Cu-Zn superoxide dismutase (SOD1) and calcineurin (Cn) interaction in ALS: A presumed consequence for TDP-43 and zinc aggregation in Tg SOD1G93A rodent spinal cord tissue.

Impaired interactions between Calcineurin (Cn) and (Cu/Zn) superoxide dismutase (SOD1) are suspected to be responsible for the formation of hyperphosphorylated protein aggregation in amyotrophic lateral sclerosis (ALS). Serine (Ser)-enriched TDP-43 protein aggregation appears in the spinal cord of ALS animal models, and may be linked to the reduced phosphatase activity of Cn. The mutant overexpressed SOD1G93A protein does not properly bind zinc (Zn) in animal models; hence, mutant SOD1G93A - Cn interaction weakens. Consequently, unstable Cn fails to dephosphorylate TDP-43 that yields hyperphosphorylated TDP-43 aggregates. Our previous studies had suggested that Cn and SOD1 interaction was necessary to keep Cn enzyme functional. We have observed low Cn level, increased Zn concentrations, and increased TDP-43 protein levels in cervical, thoracic, lumbar, and sacral regions of the spinal cord tissue homogenates. This study further supports our previous published work indicating that Cn stability depends on functional Cn-SOD1 interaction because Zn metal is crucial for maintaining the Cn stability. Less active Cn did not efficiently dephosphorylate TDP-43; hence TDP-43 aggregations appeared in the spinal cord tissue.

neuroscience↗

bioRxiv2017

Testing the principles of Mendelian randomization: Opportunities and complications on a genomewide scale

BackgroundMendelian randomization (MR) uses genetic variants as instrumental variables to assess whether observational associations between exposures and disease reflect causal relationships. MR requires genetic variants to be independent of factors that confound observational associations.\n\nMethodsUsing data from the Avon Longitudinal Study of Parents and Children, associations within and between 121 phenotypes and 13,720 genetic variants (from the NHGRI-EBI GWAS catalog) were examined to assess the validity of MR assumptions.\n\nResultsAmongst 7,260 pairwise comparisons between the 121 phenotypes, 2,188 (30%) provided evidence of association, where 363 were expected at the 5% level (observed:expected ratio=6.03; 95% CI: 5.42, 6.70; {chi}2=9682.29; d.f. =1, P[≤]1x10-50). Amongst 1,660,120 pairwise associations between phenotypes and genotypes, 86,748 (5.2%) gave evidence of association at the same threshold, where 83,006 were expected (observed:expected ratio=1.05; 95% CI: 1.04, 1.05; {chi}2=117.57; d.f. =1, P=2.15x10-27). Amongst 1,171,764 pairwise associations between the phenotypes and LD pruned independent genetic variants, 60,136 (5.1%) gave evidence of association, where 58,588 were expected (observed:expected ratio=1.03; 95% CI: 1.03, 1.08; {chi}2= 43.05; d.f. = 1, P=5.33x10-11).\n\nConclusionThese results confirm previously observed patterns of phenotypic correlation. They also provide evidence of a substantially lower level of association between genetic variants and phenotypes, with residual inflation the likely product of indistinguishable real genetic association, multiple variables measuring the same biological phenomena, or pleiotropy. These results reflect the favorable properties of genetic instruments for estimating causal relationships, but confirm the need for functional information or analytical methods to account for pleiotropic events.

epidemiology↗