Properties of developmental gene regulatory networks

The modular components, or subcircuits, of developmental gene regulatory networks (GRNs) execute specific developmental functions, such as the specification of cell identity. We survey examples of such subcircuits and relate their structures to corresponding developmental functions. These relations transcend organisms and genes, as illustrated by the similar structures of the subcircuits controlling the specification of the mesectoderm in the Drosophila embryo and the endomesoderm in the sea urchin, even though the respective subcircuits are composed of nonorthologous regulatory genes

Polyphasic feedback enables tunable cellular timers

Cellular ‘timers’ provide an important function in living cells [1]. Timers help cells defer their responses to stimuli, often for time intervals extending over multiple cell cycles (Figure 1A, left). For example, mammalian oligodendrocyte precursors typically proliferate for ∼7 divisions before differentiating during neural development [2]. The bacterium Bacillus subtilis can respond to sudden nutrient limitation by transforming into a dormant spore after ∼5 cell cycles [3]. Timers can balance proliferation with differentiation to control the sizes of various cell populations. Some timers appear to operate in a largely cell-autonomous fashion, but the underlying genetic circuit mechanisms that enable this remain poorly understood. Protein dilution poses stringent challenges to timer circuits by continually diluting out timer components in proliferating cells ( Figure 1A, right). Recent work suggests that pulsatile or oscillatory dynamics can facilitate timer functions 3 and 4. Here, we show how polyphasic positive feedback — a pulsed architecture that breaks a feedback signal into temporally distinct phases — counteracts protein dilution to facilitate timer behavior

Regulatory activity revealed by dynamic correlations in gene expression noise

Gene regulatory interactions are context dependent, active in some cellular states but not in others. Stochastic fluctuations, or 'noise', in gene expression propagate through active, but not inactive, regulatory links^(1,2). Thus, correlations in gene expression noise could provide a noninvasive means to probe the activity states of regulatory links. However, global, 'extrinsic', noise sources generate correlations even without direct regulatory links. Here we show that single-cell time-lapse microscopy, by revealing time lags due to regulation, can discriminate between active regulatory connections and extrinsic noise. We demonstrate this principle mathematically, using stochastic modeling, and experimentally, using simple synthetic gene circuits. We then use this approach to analyze dynamic noise correlations in the galactose metabolism genes of Escherichia coli. We find that the CRP-GalS-GalE feed-forward loop is inactive in standard conditions but can become active in a GalR mutant. These results show how noise can help analyze the context dependence of regulatory interactions in endogenous gene circuits

Functional Roles of Pulsing in Genetic Circuits

A fundamental problem in biology is to understand how genetic circuits implement core cellular functions. Time-lapse microscopy techniques are beginning to provide a direct view of circuit dynamics in individual living cells. Unexpectedly, we are discovering that key transcription and regulatory factors pulse on and off repeatedly, and often stochastically, even when cells are maintained in constant conditions. This type of spontaneous dynamic behavior is pervasive, appearing in diverse cell types from microbes to mammalian cells. Here, we review recent work showing how pulsing is generated and controlled by underlying regulatory circuits and how it provides critical capabilities to cells in stress response, signaling, and development. A major theme is the ability of pulsing to enable time-based regulation analogous to strategies used in engineered systems. Thus, pulsatile dynamics is emerging as a central, and still largely unexplored, layer of temporal organization in the cell

Social structures depend on innate determinants and chemosensory processing in Drosophila

Flies display transient social interactions in groups. However, whether fly–fly interactions are stochastic or structured remains unknown. We hypothesized that groups of flies exhibit patterns of social dynamics that would manifest as nonrandom social interaction networks. To test this, we applied a machine vision system to track the position and orientation of flies in an arena and designed a classifier to detect interactions between pairs of flies. We show that the vinegar fly, Drosophila melanogaster, forms nonrandom social interaction networks, distinct from virtual network controls (constructed from the intersections of individual locomotor trajectories). In addition, the formation of interaction networks depends on chemosensory cues. Gustatory mutants form networks that cannot be distinguished from their virtual network controls. Olfactory mutants form networks that are greatly disrupted compared with control flies. Different wild-type strains form social interaction networks with quantitatively different properties, suggesting that the genes that influence this network phenotype vary across and within wild-type populations. We have established a paradigm for studying social behaviors at a group level in Drosophila and expect that a genetic dissection of this phenomenon will identify conserved molecular mechanisms of social organization in other species

Emotional and Adrenocortical Responses of Infants to the Strange Situation: The Differential Function of Emotional Expression

The aim of the study was to investigate biobehavioural organisation in infants with different qualities of attachment. Quality of attachment (security and disorganisation), emotional expression, and adrenocortical stress reactivity were investigated in a sample of 106 infants observed during Ainsworth’s Strange Situation at the age of 12 months. In addition, behavioural inhibition was assessed from maternal reports. As expected, securely attached infants did not show an adrenocortical response. Regarding the traditionally defined insecurely attached groups, adrenocortical activation during the strange situation was found for the ambivalent group, but not for the avoidant one. Previous ndings of increased adrenocortical activity in disorganised infants could not be replicated. In line with previous ndings, adrenocortical activation was most prominent in insecure infants with high behavioural inhibition indicating the function of a secure attachment relationship as a social buffer against less adaptive temperamental dispositions. Additional analyses indicated that adrenocortical reactivity and behavioural distress were not based on common activation processes. Biobehavioural associations within the different attachment groups suggest that biobehavioural processes in securely attached infants may be different from those in insecurely attached and disorganised groups. Whereas a coping model may be applied to describe the biobehavioural organisation of secure infants, an arousal model explanation may be more appropriate for the other groups

Hysteresis phenomenon in deterministic traffic flows

We study phase transitions of a system of particles on the one-dimensional integer lattice moving with constant acceleration, with a collision law respecting slower particles. This simple deterministic ``particle-hopping'' traffic flow model being a straightforward generalization to the well known Nagel-Schreckenberg model covers also a more recent slow-to-start model as a special case. The model has two distinct ergodic (unmixed) phases with two critical values. When traffic density is below the lowest critical value, the steady state of the model corresponds to the ``free-flowing'' (or ``gaseous'') phase. When the density exceeds the second critical value the model produces large, persistent, well-defined traffic jams, which correspond to the ``jammed'' (or ``liquid'') phase. Between the two critical values each of these phases may take place, which can be interpreted as an ``overcooled gas'' phase when a small perturbation can change drastically gas into liquid. Mathematical analysis is accomplished in part by the exact derivation of the life-time of individual traffic jams for a given configuration of particles.Comment: 22 pages, 6 figures, corrected and improved version, to appear in the Journal of Statistical Physic

Take a Giant Step: A Blueprint for Teaching Young Children in a Digital Age

Calls for enhancing early childhood education and teacher preparation and development by incorporating digital learning and highlights best practices, policy and program trends, and innovative approaches. Outlines goals for 2020 and steps to achieve them

Investigation of growth responses in saprophytic fungi to charred biomass

We present the results of a study testing the response of two saprophytic white-rot fungi species, Pleurotus pulmonarius and Coriolus versicolor, to charred biomass (charcoal) as a growth substrate. We used a combination of optical microscopy, scanning electron microscopy, elemental abundance measurements, and isotope ratio mass spectrometry (<sup>13</sup>C and <sup>15</sup>N) to investigate fungal colonisation of control and incubated samples of Scots Pine (Pinus sylvestris) wood, and charcoal from the same species produced at 300 °C and 400 °C. Both species of fungi colonise the surface and interior of wood and charcoals over time periods of less than 70 days; however, distinctly different growth forms are evident between the exterior and interior of the charcoal substrate, with hyphal penetration concentrated along lines of structural weakness. Although the fungi were able to degrade and metabolise the pine wood, charcoal does not form a readily available source of fungal nutrients at least for these species under the conditions used in this study

Cardiac Atrophy and Diastolic Dysfunction During and After Long Duration Spaceflight: Functional Consequences for Orthostatic Intolerance, Exercise Capability and Risk for Cardiac Arrhythmias

Cardiac Atrophy and Diastolic Dysfunction During and After Long Duration Spaceflight: Functional Consequences for Orthostatic Intolerance, Exercise Capability and Risk for Cardiac Arrhythmias (Integrated Cardiovascular) will quantify the extent of long-duration space flightassociated cardiac atrophy (deterioration) on the International Space Station crewmembers