Biology subjects

Phillips, M. L.

Publications and source records attributed to Phillips, M. L..

4 recordsLinked to original sources

bioRxiv2018

Fungal community assembly in soils and roots under plant invasion and nitrogen deposition

Abstract Fungal community composition in the Anthropocene is driven by rapid changes in environmental conditions caused by human activities. This study examines the relative importance of two global change drivers - atmospheric nitrogen (N) deposition and annual grass invasion - on structuring fungal communities in a California chaparral ecosystem, with emphasis on arbuscular mycorrhizal fungi. We used molecular markers, functional groupings, generalized linear statistics and joint distribution modeling, to examine how environmental variables structure taxonomic and functional composition of fungal communities. Invasion of a chaparral ecosystem decreased richness and relative abundance of non-AMF symbionts and rhizophilic AMF (e.g. Glomeraceae) as well as the proportion of edaphophilic AMF (e.g. Gigasporaceae). We found increased richness and the proportion of rhizophilic and edaphophilic AMF with increasing soil NO3. Our findings suggest that invasive persistence may decrease the presence of multiple soil symbionts that native species depend on for pathogen protection and increased access to soil resources.

ecology↗

bioRxiv2017

t-Darpp is an elongated monomer that binds to calcium and is phosphorylated by cyclin-dependent kinases 1 and 5

t-Darpp is a protein encoded by the PPP1R1B gene and is expressed in breast, colon, esophageal, gastric, and prostate cancers, as well as in normal adult brain striatal cells. Overexpression of t-Darpp in cultured cells leads to increased protein kinase A activity and increased phosphorylation of AKT (protein kinase B). In HER2+ breast cancer cells t-Darpp confers resistance to the chemotherapeutic agent trastuzumab. To shed light on t-Darpp function, we studied its secondary structure, oligomerization status, metal-binding properties, and phosphorylation by cyclin dependent kinases 1 and 5. t-Darpp exhibits 12% alpha helix, 29% beta strand, 24% beta turn and 35% random coil structures. t-Darpp binds to calcium, but not to other metals commonly found in biological systems. The T39 site, critical for t-Darpp activation of the AKT signaling pathway, is a substrate for phosphorylation by cyclin-dependent kinase 1 (CDK1) and cyclin-dependent kinase 5 (CDK5). Gel filtration chromatography, sedimentation equilibrium analysis, blue native gel electrophoresis, and glutaraldehyde-mediated crosslinking experiments demonstrate that the majority of t-Darpp exists as a monomer, but forms low levels (< 3%) of hetero-oligomers with its longer isoform Darpp-32. t-Darpp has a large Stokes radius of 4.4 nm relative to its mass of 19 kDa, indicating that it has an elongated structure.

biochemistry↗

bioRxiv2017

The Neuron Specific Formin Delphilin Nucleates Actin Filaments but Does Not Enhance Elongation

The formin Delphilin binds the glutamate receptor, GluR{delta}2, in dendritic spines of Purkinje cells. Both proteins play a role in learning. To understand how Delphilin functions in neurons, we studied the actin assembly properties of this formin. Formins have a conserved formin homology 2 domain, which nucleates and remains associated with the fast growing end of actin filaments, influencing filament growth with input from the adjacent formin homology 1 domain. The strength of nucleation and elongation varies widely across formins. Additionally, most formins have conserved domains that regulate actin assembly through an intramolecular interaction. Delphilin is distinct from other formins in several ways: its expression is limited to Purkinje cells; it lacks autoinhibitory domains; its formin homology 1 domains has minimal proline-rich sequence. We found that Delphilin is an actin nucleator that does not accelerate elongation, although it binds tightly to the barbed end of filaments. In addition, Delphilin exhibits a preference for actin isoforms, which has not been described or systematically studied in other formins. Finally, Delphilin is the first formin studied that is not regulated by intramolecular interactions. We speculate how the activity we observe is consistent with its localization in the small dendritic spines.\n\nAbbreviations: FH1, formin homology 1; FH2, formin homology 2; DID, diaphanous inhibitory domain; DAD, diaphanous autoinhibitory domain; LTD, long term depression; PSD, post synaptic density; PDZ, post synaptic density protein (PSD95), Drosophila disc large tumor suppressor (Dlg1), and zonula occludens-1 protein (zo-1).

biochemistry↗

bioRxiv2017

Harmonization of cortical thickness measurements across scanners and sites

With the proliferation of multi-site neuroimaging studies, there is a greater need for handling non-biological variance introduced by differences in MRI scanners and acquisition protocols. Such unwanted sources of variation, which we refer to as \"scanner effects\", can hinder the detection of imaging features associated with clinical covariates of interest and cause spurious findings. In this paper, we investigate scanner effects in two large multi-site studies on cortical thickness measurements, across a total of 11 scanners. We propose a set of general tools for visualizing and identifying scanner effects that are generalizable to other modalities. We then propose to use ComBat, a technique adopted from the genomics literature and recently applied to diffusion tensor imaging data, to combine and harmonize cortical thickness values across scanners. We show that ComBat removes unwanted sources of scan variability while simultaneously increasing the power and reproducibility of subsequent statistical analyses. We also show that ComBat is useful for combining imaging data with the goal of studying life-span trajectories in the brain.

neuroscience↗