Biology subjects

Popovic, M.

Publications and source records attributed to Popovic, M..

4 recordsLinked to original sources

bioRxiv2017

Development of cross-orientation suppression and size tuning and the role of experience

Many sensory neural circuits exhibit response normalization, which occurs when the response of a neuron to a combination of multiple stimuli is less than the sum of the responses to the individual stimuli presented alone. In the visual cortex, normalization takes the forms of cross-orientation suppression and surround suppression. At the onset of visual experience, visual circuits are partially developed and exhibit some mature features such as orientation selectivity, but it is unknown whether cross-orientation suppression or surround suppression are present at the onset of visual experience or require visual experience for their emergence. We characterized the development of these properties and their dependence on visual experience in ferrets. Visual experience was varied across three conditions: typical rearing, dark rearing, and dark rearing with daily exposure to simple sinusoidal gratings (14-16 hours total). Cross-orientation suppression and surround suppression were noted in the earliest observations, and did not vary considerably with experience. We also observed evidence of continued maturation of receptive field properties in the second month of visual experience: substantial length summation was observed only in the oldest animals (postnatal day 90); evoked firing rates were greatly increased in older animals; and direction selectivity required experience, but declined slightly in older animals. These results constrain the space of possible circuit implementations of these features.\n\nSignificance StatementThe development of the brain depends on both nature - factors that are independent of the experience of an individual animal - and nurture - factors that depend on experience. While orientation selectivity, one of the major response properties of neurons in visual cortex, is already present at the onset of visual experience, it is unknown if response properties that depend on interactions among multiple stimuli develop without experience. We find that the properties of crossorientation suppression and surround suppression are present at eye opening, and do not depend on visual experience. Our results are consistent with the idea that a majority of the basic properties of sensory neurons in primary visual cortex are derived independent of the experience of an individual animal.

neuroscience↗

bioRxiv2017

Fast and Accurate Genomic Analyses using Genome Graphs

The human reference genome serves as the foundation for genomics by providing a scaffold for alignment of sequencing reads, but currently only reflects a single consensus haplotype, which impairs read alignment and downstream analysis accuracy. Reference genome structures incorporating known genetic variation have been shown to improve the accuracy of genomic analyses, but have so far remained computationally prohibitive for routine large-scale use. Here we present a graph genome implementation that enables read alignment across 2,800 diploid genomes encompassing 12.6 million SNPs and 4.0 million indels. Our Graph Genome Pipeline requires 6.5 hours to process a 30x coverage WGS sample on a system with 36 CPU cores compared with 11 hours required by the GATK Best Practices pipeline. Using complementary benchmarking experiments based on real and simulated data, we show that using a graph genome reference improves read mapping sensitivity and produces a 0.5% increase in variant calling recall, or about 20,000 additional variants being detected per sample, while variant calling specificity is unaffected. Structural variations (SVs) incorporated into a graph genome can be genotyped accurately under a unified framework. Finally, we show that iterative augmentation of graph genomes yields incremental gains in variant calling accuracy. Our implementation is a significant advance towards fulfilling the promise of graph genomes to radically enhance the scalability and accuracy of genomic analyses.

bioinformatics↗

bioRxiv2017

Cell Dynamics Underlying Oriented Growth Of The Drosophila Imaginal Wing Disc

Quantitative analysis of the dynamic cellular mechanisms shaping the Drosophila wing during its larval growth phase has been limited, impeding our ability to understand how morphogen patterns regulate tissue shape. Such analysis requires imaging explants under conditions that maintain both growth and patterning, as well as methods to quantify how much cellular behaviors change tissue shape. Here, we demonstrate a key requirement for the steroid hormone 20-hydroxyecdysone (20E) in the maintenance of numerous patterning systems in vivo and in explant culture. We find that low concentrations of 20E support prolonged proliferation in explanted wing discs in the absence of insulin, incidentally providing novel insight into the hormonal regulation of imaginal growth. We use 20E-containing media to directly observe growth and apply recently developed methods for quantitatively decomposing tissue shape changes into cellular contributions. We discover that while cell divisions drive tissue expansion along one axis, their contribution to expansion along the orthogonal axis is cancelled by cell rearrangements and cell shape changes. This finding raises the possibility that anisotropic mechanical constraints contribute to growth orientation in the wing disc.

developmental biology↗

bioRxiv2016

Perfluorooctane sulfonate affects proliferation and differentiation of pluripotent human teratocarcinoma cells

Perfluorinated compounds have raised concern due to their potential association with detrimental postnatal outcomes in animals and humans. We tested the effects of perfluorooctane sulfonate (PFOS) on a human pluripotent teratocarcinoma (known as NCCIT) cells as an in vitro prototype for developmental toxicity in mammals. NCCIT contains stem-cells able to differentiate into endoderm, mesoderm and ectoderm. We tested our cell model using a teratogenic compound, retinoic acid (RA), a cytotoxin, nocodazole (ND), and PFOS. We assayed cells proliferation, morphology and expression of stem cell and germ layer marker genes. PFOS reduced NCCIT cell proliferation in a concentration-dependent manner and induced morphological changes in cell cultures that resembled ectodermal phenotypes. A tendency towards a differentiated state in NCCIT was confirmed by real-time gene expression. PFOS triggered up-regulation of the gene nestin, indicative of ectodermal lineage differentiation, and interfered with the expression of the pluripotency stem-cell marker TERT. PFOS produced effects on both cells proliferation and differentiation, although not as severe as those observed for RA and ND, at levels that fall within the range of concentrations found in animal and human plasma. We discuss our findings in the context of possible interference of PFOS with the processes governing the early development of mammalian tissues.

pharmacology and toxicology↗