A comprehensive molecular interaction map of the budding yeast cell cycle

With the accumulation of data on complex molecular machineries coordinating cell-cycle dynamics, coupled with its central function in disease patho-physiologies, it is becoming increasingly important to collate the disparate knowledge sources into a comprehensive molecular network amenable to systems-level analyses. In this work, we present a comprehensive map of the budding yeast cell-cycle, curating reactions from ∼600 original papers. Toward leveraging the map as a framework to explore the underlying network architecture, we abstract the molecular components into three planes—signaling, cell-cycle core and structural planes. The planar view together with topological analyses facilitates network-centric identification of functions and control mechanisms. Further, we perform a comparative motif analysis to identify around 194 motifs including feed-forward, mutual inhibitory and feedback mechanisms contributing to cell-cycle robustness. We envisage the open access, comprehensive cell-cycle map to open roads toward community-based deeper understanding of cell-cycle dynamics

A Microtubule Interactome: Complexes with Roles in Cell Cycle and Mitosis

The microtubule (MT) cytoskeleton is required for many aspects of cell function, including the transport of intracellular materials, the maintenance of cell polarity, and the regulation of mitosis. These functions are coordinated by MT-associated proteins (MAPs), which work in concert with each other, binding MTs and altering their properties. We have used a MT cosedimentation assay, combined with 1D and 2D PAGE and mass spectrometry, to identify over 250 MAPs from early Drosophila embryos. We have taken two complementary approaches to analyse the cellular function of novel MAPs isolated using this approach. First, we have carried out an RNA interference (RNAi) screen, identifying 21 previously uncharacterised genes involved in MT organisation. Second, we have undertaken a bioinformatics analysis based on binary protein interaction data to produce putative interaction networks of MAPs. By combining both approaches, we have identified and validated MAP complexes with potentially important roles in cell cycle regulation and mitosis. This study therefore demonstrates that biologically relevant data can be harvested using such a multidisciplinary approach, and identifies new MAPs, many of which appear to be important in cell division

Beyond BMI for self-estimates of body size and shape: A new method for developing stimuli correctly calibrated for body composition

Accurate self-assessment of body shape and size plays a key role in the prevention, diagnosis, and treatment of both obesity and eating disorders. These chronic conditions cause significant health problems, reduced quality of life, and represent a major problem for health services. Variation in body shape depends on two aspects of composition: adiposity and muscularity. However, most self-assessment tools are unidimensional. They depict variation in adiposity only, typically quantified by the body mass index. This can lead to substantial, and clinically meaningful, errors in estimates of body shape and size. To solve this problem, we detail a method of creating biometrically valid body stimuli. We obtained high-resolution 3D body shape scans and composition measures from 397 volunteers (aged 18–45 years) and produced a statistical mapping between the two. This allowed us to create 3D computer-generated models of bodies, correctly calibrated for body composition (i.e., muscularity and adiposity). We show how these stimuli, whose shape changes are based on change in composition in two dimensions, can be used to match the body size and shape participants believe themselves to have, to the stimulus they see. We also show how multivariate multiple regression can be used to model shape change predicted by these 2D outcomes, so that participants’ choices can be explained by their measured body composition together with other psychometric variables. Together, this approach should substantially improve the accuracy and precision with which self-assessments of body size and shape can be made in obese individuals and those suffering from eating disorders

Bio-Inspired Materials For Parsing Matrix Physicochemical Control Of Cell Migration: A Review

Cell motility is ubiquitous in both normal and pathophysiological processes. It is a complex biophysical response elicited via the integration of diverse extracellular physicochemical cues. The extracellular matrix directs cell motilityvia gradients in morphogens (a.k.a. chemotaxis), adhesive proteins (haptotaxis), and stiffness (durotaxis). Three-dimensional geometrical and proteolytic cues also constitute key regulators of motility. Therefore, cells process a variety of physicochemical signals simultaneously, while making informed decisions about migration viaintracellular processing. Over the last few decades, bioengineers have created and refined natural and synthetic in vitro platforms in an attempt to isolate these extracellular cues and tease out how cells are able to translate this complex array of dynamic biochemical and biophysical features into functional motility. Here, we review how biomaterials have played a key role in the development of these types of model systems, and how recent advances in engineered materials have significantly contributed to our current understanding of the mechanisms of cell migration