Quantitative analysis of regulatory flexibility under changing environmental conditions.

The circadian clock controls 24-h rhythms in many biological processes, allowing appropriate timing of biological rhythms relative to dawn and dusk. Known clock circuits include multiple, interlocked feedback loops. Theory suggested that multiple loops contribute the flexibility for molecular rhythms to track multiple phases of the external cycle.

Effects of selection and mutation on mitochondrial variation and inferences of historical population expansion in a Caribbean reef fish.

Mitochondrial sequence data has contributed to the understanding of historical demography through the application of neutrality tests and coalescent estimators of population growth rates. Characteristics of the mitochondrial genome, such as high mutation rate and lack of recombination, render it particularly suitable for these types of studies. However, selection can also affect patterns of mitochondrial variation.

Physiological levels of TNFalpha stimulation induce stochastic dynamics of NF-kappaB responses in single living cells.

Nuclear factor kappa B (NF-kappaB) signalling is activated by cellular stress and inflammation and regulates cytokine expression. We applied single-cell imaging to investigate dynamic responses to different doses of tumour necrosis factor alpha (TNFalpha). Lower doses activated fewer cells and those responding showed an increasingly variable delay in the initial NF-kappaB nuclear translocation and associated IkappaBalpha degradation.

Mitochondrial-nuclear epistasis affects fitness within species but does not contribute to fixed incompatibilities between species of Drosophila.

Efficient mitochondrial function requires physical interactions between the proteins encoded by the mitochondrial and nuclear genomes. Coevolution between these genomes may result in the accumulation of incompatibilities between divergent lineages. We test whether mitochondrial-nuclear incompatibilities have accumulated within the Drosophila melanogaster species subgroup by combining divergent mitochondrial and nuclear lineages and quantifying the effects on relative fitness.

Emotions as infectious diseases in a large social network: the SISa model.

Human populations are arranged in social networks that determine interactions and influence the spread of diseases, behaviours and ideas. We evaluate the spread of long-term emotional states across a social network. We introduce a novel form of the classical susceptible-infected-susceptible disease model which includes the possibility for 'spontaneous' (or 'automatic') infection, in addition to disease transmission (the SISa model).

Robustness from flexibility in the fungal circadian clock.

Background: Robustness is a central property of living systems, enabling function to be maintained against environmental perturbations. A key challenge is to identify the structures in biological circuits that confer system-level properties such as robustness. Circadian clocks allow organisms to adapt to the predictable changes of the 24-hour day/night cycle by generating endogenous rhythms that can be entrained to the external cycle.

Prevalence of resident burnout at the start of training.

Background: Job burnout is characterized by emotional exhaustion, depersonalization, and feelings of decreased personal accomplishment, and it may be linked to depression and suboptimal patient care. Burnout among American internal medicine residents ranges between 55% and 76%.

Purpose: We aim to further characterize burnout prevalence at the start of residency.

Using a single fluorescent reporter gene to infer half-life of extrinsic noise and other parameters of gene expression.

Fluorescent and luminescent proteins are often used as reporters of transcriptional activity. Given the prevalence of noise in biochemical systems, the time-series data arising from these is of significant interest in efforts to calibrate stochastic models of gene expression and obtain information about sources of nongenetic variability. We present a statistical inference framework that can be used to estimate kinetic parameters of gene expression, as well as the strength and half-life of extrinsic noise from single fluorescent-reporter-gene time-series data.

Anti-social punishment can prevent the co-evolution of punishment and cooperation.

The evolution of cooperation is one of the great puzzles in evolutionary biology. Punishment has been suggested as one solution to this problem. Here punishment is generally defined as incurring a cost to inflict harm on a wrong-doer.

Measurement of single-cell dynamics.

Populations of cells are almost always heterogeneous in function and fate. To understand the plasticity of cells, it is vital to measure quantitatively and dynamically the molecular processes that underlie cell-fate decisions in single cells. Early events in cell signalling often occur within seconds of the stimulus, whereas intracellular signalling processes and transcriptional changes can take minutes or hours.

Population robustness arising from cellular heterogeneity.

Heterogeneity between individual cells is a common feature of dynamic cellular processes, including signaling, transcription, and cell fate; yet the overall tissue level physiological phenotype needs to be carefully controlled to avoid fluctuations. Here we show that in the NF-kappaB signaling system, the precise timing of a dual-delayed negative feedback motif [involving stochastic transcription of inhibitor kappaB (IkappaB)-alpha and -epsilon] is optimized to induce heterogeneous timing of NF-kappaB oscillations between individual cells. We suggest that this dual-delayed negative feedback motif enables NF-kappaB signaling to generate robust single cell oscillations by reducing sensitivity to key parameter perturbations.

Three selections are better than one: clinal variation of thermal QTL from independent selection experiments in Drosophila.

We report the results of two independent selection experiments that have exposed distinct populations of Drosophila melanogaster to different forms of thermal selection. A recombinant population derived from Arvin California and Zimbabwe isofemale lines was exposed to laboratory natural selection at two temperatures (T(AZ): 18°C and 28°C). Microsatellite mapping identified quantitative trait loci (QTL) on the X-chromosome between the replicate "Hot" and "Cold" populations.

Neuroanatomy and neurophysiology of the locust hypocerebral ganglion.

The insect stomatogastric ganglia control foregut movements. Most previous work on the system has concentrated on the frontal ganglion (FG), including research into the role of the FG in feeding as well as molting-related behavior, mostly in locusts, but also in other insect species. The stomatogastric system exerts its physiological actions by way of careful interaction and coordination between its different neural centers and pattern-generating circuits.

Identification of methylmercury tolerance gene candidates in Drosophila.

Methylmercury (MeHg) is a ubiquitous environmental contaminant that preferentially targets the developing nervous system. Variable outcomes of prenatal MeHg exposure within a population point to a genetic component that regulates MeHg toxicity. We therefore sought to identify fundamental MeHg tolerance genes using the Drosophila model for genetic and molecular dissection of a MeHg tolerance trait.

The dynamic architecture of the metabolic switch in Streptomyces coelicolor.

Background: During the lifetime of a fermenter culture, the soil bacterium S. coelicolor undergoes a major metabolic switch from exponential growth to antibiotic production. We have studied gene expression patterns during this switch, using a specifically designed Affymetrix genechip and a high-resolution time-series of fermenter-grown samples.

Prediction of photoperiodic regulators from quantitative gene circuit models.

Photoperiod sensors allow physiological adaptation to the changing seasons. The prevalent hypothesis is that day length perception is mediated through coupling of an endogenous rhythm with an external light signal. Sufficient molecular data are available to test this quantitatively in plants, though not yet in mammals.

Systematic differences in impact across publication tracks at PNAS.

Background: Citation data can be used to evaluate the editorial policies and procedures of scientific journals. Here we investigate citation counts for the three different publication tracks of the Proceedings of the National Academy of Sciences of the United States of America (PNAS). This analysis explores the consequences of differences in editor and referee selection, while controlling for the prestige of the journal in which the papers appear.

Bayesian inference of biochemical kinetic parameters using the linear noise approximation.

Background: Fluorescent and luminescent gene reporters allow us to dynamically quantify changes in molecular species concentration over time on the single cell level. The mathematical modeling of their interaction through multivariate dynamical models requires the development of effective statistical methods to calibrate such models against available data. Given the prevalence of stochasticity and noise in biochemical systems inference for stochastic models is of special interest.

Positive interactions promote public cooperation.

The public goods game is the classic laboratory paradigm for studying collective action problems. Each participant chooses how much to contribute to a common pool that returns benefits to all participants equally. The ideal outcome occurs if everybody contributes the maximum amount, but the self-interested strategy is not to contribute anything.

Comparative genomics of Drosophila mtDNA: Novel features of conservation and change across functional domains and lineages.

To gain insight on mitochondrial DNA (mtDNA) evolution, we assembled and analyzed the mitochondrial genomes of Drosophila erecta, D. ananassae, D. persimilis, D.

Pulsatile stimulation determines timing and specificity of NF-kappaB-dependent transcription.

The nuclear factor kappaB (NF-kappaB) transcription factor regulates cellular stress responses and the immune response to infection. NF-kappaB activation results in oscillations in nuclear NF-kappaB abundance. To define the function of these oscillations, we treated cells with repeated short pulses of tumor necrosis factor-alpha at various intervals to mimic pulsatile inflammatory signals.

Dynamic remodeling of in-group bias during the 2008 presidential election.

People often favor members of their own group, while discriminating against members of other groups. Such in-group favoritism has been shown to play an important role in human cooperation. However, in the face of changing conflicts and shifting alliances, it is essential for group identities to be flexible.

Dual positive and negative regulation of GPCR signaling by GTP hydrolysis.

G protein-coupled receptors (GPCRs) regulate a variety of intracellular pathways through their ability to promote the binding of GTP to heterotrimeric G proteins. Regulator of G protein signaling (RGS) proteins increases the intrinsic GTPase activity of Galpha-subunits and are widely regarded as negative regulators of G protein signaling. Using yeast we demonstrate that GTP hydrolysis is not only required for desensitization, but is essential for achieving a high maximal (saturated level) response.