Biology subjects

Williams, T. D.

Publications and source records attributed to Williams, T. D..

3 recordsLinked to original sources

bioRxiv2018

Akt kinases are required for efficient feeding by macropinocytosis in Dictyostelium

Macropinocytosis is an actin-driven process of large-scale, non-specific fluid uptake used for feeding by some cancer cells and the macropinocytosis model organism Dictyostelium discoideum. In Dictyostelium, macropinocytic cups are organised by macropinocytic patches in the plasma membrane. These contain activated Ras, Rac and PI(3,4,5)P3 and direct actin polymerisation to their periphery. Here, we show that a classical (PkbA) and a variant (PkbR1) Akt protein kinase acting downstream of PI(3,4,5)P3 are together are near-essential for fluid uptake. This pathway enables the formation of larger macropinocytic patches and macropinosomes, thereby dramatically increasing fluid uptake. Akt targets identified by phosphoproteomics were highly enriched in small G-protein regulators, including the RhoGAP GacG. GacG knockout mutants make few macropinosomes but instead redeploy their cytoskeleton from macropinocytosis to motility, moving rapidly but taking up little fluid. The function of Akt in cell feeding through control of macropinosome size has implications for cancer cell biology.\n\nSummary statementDictyostelium amoebae feed by macropinocytosis in a PIP3 dependent manner. In the absence of PI3-kinases or the downstream Akt protein kinases, cells have smaller macropinosomes and nearly abolished fluid uptake.

cell biology↗

bioRxiv2018

Physiological predictors of reproductive performance in the European Starling (Sturnus vulgaris): II. Multivariate Analysis

Physiological variation is generally thought or supposed to underlie variation in fitness related traits in wild animals, including reproductive effort, reproductive success, and survival. However, physiological markers of individual quality have proven elusive. In this paper and its companion, we use data on 14 physiological parameters measured in 152 observations of 93 individual European starlings (Sturnus vulgaris) over 2 years in an attempt to understand how physiological variation relates to variation in current breeding productivity, future fecundity, and survival. The companion paper, focusing on univariate analysis, showed that individual physiological parameters have little relationship with these performance measures. Here, we used more sophisticated statistical approaches in an attempt to extract a multivariate signal from the biomarkers - physiological dysregulation as calculated via statistical distance, and a number of principal components analysis approaches. Broadly speaking, there was a surprising lack of association between physiology and performance: while some physiological summary measures were associated with some performance measures, the associations were not particularly strong or robust given the large number of statistical tests conducted. This implies either that there are relatively few links between physiology and performance, or, more likely, that the complexity of these relationships exceeds our ability to measure and model it, even using state-of-the-art statistical approaches. This is likely particularly true because our population was quite heterogeneous; we nonetheless urge caution regarding the over-interpretation of isolated significant findings in the literature.

ecology↗

bioRxiv2018

Physiological predictors of reproductive performance in the European Starling (Sturnus vulgaris): I. Univariate analysis

Costs of reproduction are assumed to be widespread, and to have a physiological basis, but the mechanisms driving decreased survival and future fecundity remain elusive. Our overall goals were to assess whether physiological variables are related to workload ability or immediate fitness consequences and if they mediate future survival or reproductive success. We investigated individual variation in physiological state at two breeding stages (incubation, chick-rearing) in female European starlings (Sturnus vulgaris), for first-and second-broods over two years. Specifically, we measured a suite of 13 physiological traits related to aerobic/metabolic capacity, oxidative stress and muscle damage, intermediary metabolism and energy supply, and immune function. We tested for relationships to traits for workload (e.g. nest visit rate) and fitness (current reproduction, survival and future reproduction).\n\nThere was little co-variation among the 13 physiological traits, either in incubating or chick-rearing birds. There were some systematic differences in incubation versus chick-rearing physiology. Chick-rearing birds had lower hematocrit and plasma creatine kinase but higher hemoglobin, triglyceride and uric acid levels. Only plasma corticosterone was repeatable between incubation and chick-rearing. We assessed relationships in a univariate manner, and found very few significant relationships between incubation or chick-rearing physiology and measures of workload, current productivity, future fecundity or survival. Variability in ecological context may complicate the relationship between physiology and behavior. Additionally, individuals may regulate different aspects of their physiology independently, making detection of physiological mediators of cost of reproduction difficult. In a companion paper (Cohen et al. submitted) we explore the utility of multivariate analysis (Principal Components Analysis, Mahalanobis distance) of the same data to account for potentially complex physiological integration.

ecology↗