Associative memory in gene regulation networks

The pattern of gene expression in the phenotype of an organism is determined in part by the dynamical attractors of the organism’s gene regulation network. Changes to the connections in this network over evolutionary time alter the adult gene expression pattern and hence the fitness of the organism. However, the evolution of structure in gene expression networks (potentially reflecting past selective environments) and its affordances and limitations with respect to enhancing evolvability is poorly understood in general. In this paper we model the evolution of a gene regulation network in a controlled scenario. We show that selected changes to connections in the regulation network make the currently selected gene expression pattern more robust to environmental variation. Moreover, such changes to connections are necessarily ‘Hebbian’ – ‘genes that fire together wire together’ – i.e. genes whose expression is selected for in the same selective environments become co-regulated. Accordingly, in a manner formally equivalent to well-understood learning behaviour in artificial neural networks, a gene expression network will therefore develop a generalised associative memory of past selected phenotypes. This theoretical framework helps us to better understand the relationship between homeostasis and evolvability (i.e. selection to reduce variability facilitates structured variability), and shows that, in principle, a gene regulation network has the potential to develop ‘recall’ capabilities normally reserved for cognitive systems

Adaptation without natural selection

Document is itself an extended abstract

Influence of anticipatory processing on visual and verbal working memory task performance

Cognitive models of Social Anxiety Disorder (SAD; e.g., Clark & Wells, 1995) have implicated anticipatory processing, an anxiety-related form of repetitive negative thinking, in the maintenance of SAD symptoms. However, research has yet to examine potential mechanisms responsible for symptom maintenance. In the current study, participants high (HSA; N = 45) and low (LSA; N = 45) in social anxiety symptoms engaged in either an anticipatory processing or distraction task and then completed verbal and visual working memory tasks. HSAs who engaged in anticipatory processing demonstrated lower performance on the visual working memory task relative to the other groups, suggesting that anticipatory processing impairs visual working memory. There were no differences among any groups on verbal working memory task scores. This study advances the literature on the importance of imagery in SAD. It also underscores importance of examining anticipatory processing in the social anxiety and repetitive negative thinking literatures

If you can't be with the one you love, love the one you're with: How individual habituation of agent interactions improves global utility

Simple distributed strategies that modify the behaviour of selfish individuals in a manner that enhances cooperation or global efficiency have proved difficult to identify. We consider a network of selfish agents who each optimise their individual utilities by coordinating (or anti-coordinating) with their neighbours, to maximise the pay-offs from randomly weighted pair-wise games. In general, agents will opt for the behaviour that is the best compromise (for them) of the many conflicting constraints created by their neighbours, but the attractors of the system as a whole will not maximise total utility. We then consider agents that act as 'creatures of habit' by increasing their preference to coordinate (anti-coordinate) with whichever neighbours they are coordinated (anti-coordinated) with at the present moment. These preferences change slowly while the system is repeatedly perturbed such that it settles to many different local attractors. We find that under these conditions, with each perturbation there is a progressively higher chance of the system settling to a configuration with high total utility. Eventually, only one attractor remains, and that attractor is very likely to maximise (or almost maximise) global utility. This counterintutitve result can be understood using theory from computational neuroscience; we show that this simple form of habituation is equivalent to Hebbian learning, and the improved optimisation of global utility that is observed results from wellknown generalisation capabilities of associative memory acting at the network scale. This causes the system of selfish agents, each acting individually but habitually, to collectively identify configurations that maximise total utility

The challenges of achieving high training coverage for IMCI: case studies from Kenya and Tanzania

Health worker training is a key component of the integrated management of childhood illness (IMCI). However, training coverage remains low in many countries. We conducted in-depth case studies in two East African countries to examine the factors underlying low training coverage 10 years after IMCI had been adopted as policy. A document review and in-depth semi-structured interviews with stakeholders at facility, district, regional/provincial and national levels in two districts in Kenya (Homa Bay and Malindi) and Tanzania (Bunda and Tarime) were carried out in 2007–08

The Molecular ISM in the Super Star Clusters of the Starburst NGC 253

We present submillimeter spectra of the (proto-)super star cluster (SSC) candidates in the starbursting center of the nearby galaxy NGC 253 identified by Leroy et al. (2018). The 2.5pc resolution of our ALMA cycle 3 observations approach the size of the SSCs and allows the study of physical and chemical properties of the molecular gas in these sources. In the 14 SSC sources and in the frequency ranges 342.0-345.8 GHz and 353.9-357.7 GHz we detect 55 lines belonging to 19 different chemical species. The SSCs differ significantly in chemical complexity, with the richest clusters showing 19 species and the least complex showing 4 species. We detect HCN isotopologues and isomers (H$^{13}$CN, HC$^{15}$N, H$^{15}$NC), abundant HC$_3$N, SO and S$^{18}$O, SO$_2$, and H$_2$CS. The gas ratios CO/HCN, CO/HCO$^+$ are low, ~1-10, implying high dense gas fractions in the SSCs. Line ratio analyses suggests chemistry consistent with photon-dominated regions and mechanical heating. None of the SSCs near the galaxy center show line ratios that imply an X-ray dominated region, suggesting that heating by any (still unknown) AGN does not play a major role. The gas temperatures are high in most sources, with an average rotational temperature of ~130 K in SO$_2$. The widespread existence of vibrationally excited HCN and HC$_3$N transitions implies strong IR radiation fields, potentially trapped by a greenhouse effect due to high continuum opacities.Comment: 20 pages, 4 figures, 6 tables; accepted for publication in the Astrophysical Journa

Forming Super Star Clusters in the Central Starburst of NGC 253

NGC 253 hosts the nearest nuclear starburst. Previous observations show a region rich in molecular gas, with dense clouds associated with recent star formation. We used the Atacama Large Submillimeter/Millimeter Array (ALMA) to image the 350 GHz dust continuum and molecular line emission from this region at 2 pc resolution. Our observations reveal similar to 14 bright, compact (similar to 2-3 pc FWHM) knots of dust emission. Most of these sources are likely to be forming super star clusters (SSCs) based on their inferred dynamical and gas masses, association with 36 GHz radio continuum emission, and coincidence with line emission tracing dense, excited gas. One source coincides with a known SSC, but the rest remain invisible in Hubble near-infrared (IR) imaging. Our observations imply that gas still constitutes a large fraction of the overall mass in these sources. Their high brightness temperature at 350 GHz also implies a large optical depth near the peak of the IR spectral energy distribution. As a result, these sources may have large IR photospheres, and the IR radiation force likely exceeds L/c. Still, their moderate observed velocity dispersions suggest that feedback from radiation, winds, and supernovae are not yet disrupting most sources. This mode of star formation appears to produce a large fraction of stars in the burst. We argue for a scenario in which this phase lasts similar to 1 Myr, after which the clusters shed their natal cocoons but continue to produce ionizing photons. The strong feedback that drives the observed cold gas and X-ray outflows likely occurs after the clusters emerge from this early phase.Peer reviewe