The \u3cem\u3elet-7\u3c/em\u3e MicroRNA Family Members \u3cem\u3emir\u3c/em\u3e-48, \u3cem\u3emir\u3c/em\u3e-84, and mir-241 Function Together to Regulate Developmental Timing in \u3cem\u3eCaenorhabditis elegans\u3c/em\u3e

The microRNA let-7 is a critical regulator of developmental timing events at the larval-to-adult transition in C. elegans. Recently, microRNAs with sequence similarity to let-7 have been identified. We find that doubly mutant animals lacking the let-7 family microRNA genes mir-48 and mir-84 exhibit retarded molting behavior and retarded adult gene expression in the hypodermis. Triply mutant animals lacking mir-48, mir-84, and mir-241 exhibit repetition of L2-stage events in addition to retarded adult-stage events. mir-48, mir-84, and mir-241 function together to control the L2-to-L3 transition, likely by base pairing to complementary sites in the hbl-1 3′ UTR and downregulating hbl-1 activity. Genetic analysis indicates that mir-48, mir-84, and mir-241 specify the timing of the L2-to-L3 transition in parallel to the heterochronic genes lin-28 and lin-46. These results indicate that let-7 family microRNAs function in combination to affect both early and late developmental timing decisions

Most \u3cem\u3eCaenorhabditis elegans\u3c/em\u3e MicroRNAs are Individually Not Essential for Development or Viability

MicroRNAs (miRNAs), a large class of short noncoding RNAs found in many plants and animals, often act to post-transcriptionally inhibit gene expression. We report the generation of deletion mutations in 87 miRNA genes in Caenorhabditis elegans, expanding the number of mutated miRNA genes to 95, or 83% of known C. elegans miRNAs. We find that the majority of miRNAs are not essential for the viability or development of C. elegans, and mutations in most miRNA genes do not result in grossly abnormal phenotypes. These observations are consistent with the hypothesis that there is significant functional redundancy among miRNAs or among gene pathways regulated by miRNAs. This study represents the first comprehensive genetic analysis of miRNA function in any organism and provides a unique, permanent resource for the systematic study of miRNAs

On Counting Triangles through Edge Sampling in Large Dynamic Graphs

Traditional frameworks for dynamic graphs have relied on processing only the stream of edges added into or deleted from an evolving graph, but not any additional related information such as the degrees or neighbor lists of nodes incident to the edges. In this paper, we propose a new edge sampling framework for big-graph analytics in dynamic graphs which enhances the traditional model by enabling the use of additional related information. To demonstrate the advantages of this framework, we present a new sampling algorithm, called Edge Sample and Discard (ESD). It generates an unbiased estimate of the total number of triangles, which can be continuously updated in response to both edge additions and deletions. We provide a comparative analysis of the performance of ESD against two current state-of-the-art algorithms in terms of accuracy and complexity. The results of the experiments performed on real graphs show that, with the help of the neighborhood information of the sampled edges, the accuracy achieved by our algorithm is substantially better. We also characterize the impact of properties of the graph on the performance of our algorithm by testing on several Barabasi-Albert graphs.Comment: A short version of this article appeared in Proceedings of the 2017 IEEE/ACM International Conference on Advances in Social Networks Analysis and Mining (ASONAM 2017

Invasion speeds for structured populations in fluctuating environments

We live in a time where climate models predict future increases in environmental variability and biological invasions are becoming increasingly frequent. A key to developing effective responses to biological invasions in increasingly variable environments will be estimates of their rates of spatial spread and the associated uncertainty of these estimates. Using stochastic, stage-structured, integro-difference equation models, we show analytically that invasion speeds are asymptotically normally distributed with a variance that decreases in time. We apply our methods to a simple juvenile-adult model with stochastic variation in reproduction and an illustrative example with published data for the perennial herb, \emph{Calathea ovandensis}. These examples buttressed by additional analysis reveal that increased variability in vital rates simultaneously slow down invasions yet generate greater uncertainty about rates of spatial spread. Moreover, while temporal autocorrelations in vital rates inflate variability in invasion speeds, the effect of these autocorrelations on the average invasion speed can be positive or negative depending on life history traits and how well vital rates ``remember'' the past

Receptors and Other Signaling Proteins Required for Serotonin Control of Locomotion in Caenorhabditis elegans

A better understanding of the molecular mechanisms of signaling by the neurotransmitter serotonin is required to assess the hypothesis that defects in serotonin signaling underlie depression in humans. Caenorhabditis elegans uses serotonin as a neurotransmitter to regulate locomotion, providing a genetic system to analyze serotonin signaling. From large-scale genetic screens we identified 36 mutants of C. elegans in which serotonin fails to have its normal effect of slowing locomotion, and we molecularly identified eight genes affected by 19 of the mutations. Two of the genes encode the serotonin-gated ion channel MOD-1 and the G-protein-coupled serotonin receptor SER-4. mod-1 is expressed in the neurons and muscles that directly control locomotion, while ser-4 is expressed in an almost entirely non-overlapping set of sensory and interneurons. The cells expressing the two receptors are largely not direct postsynaptic targets of serotonergic neurons. We analyzed animals lacking or overexpressing the receptors in various combinations using several assays for serotonin response. We found that the two receptors act in parallel to affect locomotion. Our results show that serotonin functions as an extrasynaptic signal that independently activates multiple receptors at a distance from its release sites and identify at least six additional proteins that appear to act with serotonin receptors to mediate serotonin response.National Institutes of Health (U.S.) (Grant GM24663

Reinforcement learning or active inference?

This paper questions the need for reinforcement learning or control theory when optimising behaviour. We show that it is fairly simple to teach an agent complicated and adaptive behaviours using a free-energy formulation of perception. In this formulation, agents adjust their internal states and sampling of the environment to minimize their free-energy. Such agents learn causal structure in the environment and sample it in an adaptive and self-supervised fashion. This results in behavioural policies that reproduce those optimised by reinforcement learning and dynamic programming. Critically, we do not need to invoke the notion of reward, value or utility. We illustrate these points by solving a benchmark problem in dynamic programming; namely the mountain-car problem, using active perception or inference under the free-energy principle. The ensuing proof-of-concept may be important because the free-energy formulation furnishes a unified account of both action and perception and may speak to a reappraisal of the role of dopamine in the brain

Explicating "Implicit Interaction" : An Examination of the Concept and Challenges for Research

The term implicit interaction is often used to denote interactions that differ from traditional purposeful and attention demanding ways of interacting with computers. However, there is a lack of agreement about the term's precise meaning. This paper develops implicit interaction further as an analytic concept and identifies the methodological challenges related to HCI's particular design orientation. We first review meanings of implicit as unintentional, attentional background, unawareness, unconsciousness and implicature, and compare them in regards to the entity they qualify, the design motivation they emphasize and their constructive validity for what makes good interaction. We then demonstrate how the methodological challenges can be addressed with greater precision by using an updated, intentionality-based definition that specifies an input-effect relationship as the entity of implicit. We conclude by identifying a number of new considerations for design and evaluation, and by reflecting on the concepts of user and system agency in HCI.Peer reviewe

Dynamic nuclear polarization and spin-diffusion in non-conducting solids

There has been much renewed interest in dynamic nuclear polarization (DNP), particularly in the context of solid state biomolecular NMR and more recently dissolution DNP techniques for liquids. This paper reviews the role of spin diffusion in polarizing nuclear spins and discusses the role of the spin diffusion barrier, before going on to discuss some recent results.Comment: submitted to Applied Magnetic Resonance. The article should appear in a special issue that is being published in connection with the DNP Symposium help in Nottingham in August 200