Myoinhibitory peptide regulates feeding in the marine annelid Platynereis

BACKGROUND: During larval settlement and metamorphosis, marine invertebrates undergo changes in habitat, morphology, behavior and physiology. This change between life-cycle stages is often associated with a change in diet or a transition between a non-feeding and a feeding form. How larvae regulate changes in feeding during this life-cycle transition is not well understood. Neuropeptides are known to regulate several aspects of feeding, such as food search, ingestion and digestion. The marine annelid Platynereis dumerilii has a complex life cycle with a pelagic non-feeding larval stage and a benthic feeding postlarval stage, linked by the process of settlement. The conserved neuropeptide myoinhibitory peptide (MIP) is a key regulator of larval settlement behavior in Platynereis. Whether MIP also regulates the initiation of feeding, another aspect of the pelagic-to-benthic transition in Platynereis, is currently unknown. RESULTS: Here, we explore the contribution of MIP to the regulation of feeding behavior in settled Platynereis postlarvae. We find that in addition to expression in the brain, MIP is expressed in the gut of developing larvae in sensory neurons that densely innervate the hindgut, the foregut, and the midgut. Activating MIP signaling by synthetic neuropeptide addition causes increased gut peristalsis and more frequent pharynx extensions leading to increased food intake. Conversely, morpholino-mediated knockdown of MIP expression inhibits feeding. In the long-term, treatment of Platynereis postlarvae with synthetic MIP increases growth rate and results in earlier cephalic metamorphosis. CONCLUSIONS: Our results show that MIP activates ingestion and gut peristalsis in Platynereis postlarvae. MIP is expressed in enteroendocrine cells of the digestive system suggesting that following larval settlement, feeding may be initiated by a direct sensory-neurosecretory mechanism. This is similar to the mechanism by which MIP induces larval settlement. The pleiotropic roles of MIP may thus have evolved by redeploying the same signaling mechanism in different aspects of a life-cycle transition. ELECTRONIC SUPPLEMENTARY MATERIAL: The online version of this article (doi:10.1186/s12983-014-0093-6) contains supplementary material, which is available to authorized users

Rapid Phospho-Turnover by Receptor Tyrosine Kinases Impacts Downstream Signaling and Drug Binding

Epidermal growth factor receptors (ErbB1–4) are oncogenic receptor tyrosine kinases (RTKs) that regulate diverse cellular processes. In this study, we combine measurement and mathematical modeling to quantify phospho-turnover at ErbB receptors in human cells and to determine the consequences for signaling and drug binding. We find that phosphotyrosine residues on ErbB1 have half-lives of a few seconds and therefore turn over 100–1000 times in the course of a typical immediate-early response to ligand. Rapid phospho-turnover is also observed for EGF-activated ErbB2 and ErbB3, unrelated RTKs, and multiple intracellular adaptor proteins and signaling kinases. Thus, the complexes formed on the cytoplasmic tail of active receptors and the downstream signaling kinases they control are highly dynamic and antagonized by potent phosphatases. We develop a kinetic scheme for binding of anti-ErbB1 drugs to receptors and show that rapid phospho-turnover significantly impacts their mechanisms of action.National Institutes of Health (U.S.) (Grant GM68762)National Institutes of Health (U.S.) (Grant CA112967

Markov chain aggregation and its application to rule-based modelling

Rule-based modelling allows to represent molecular interactions in a compact and natural way. The underlying molecular dynamics, by the laws of stochastic chemical kinetics, behaves as a continuous-time Markov chain. However, this Markov chain enumerates all possible reaction mixtures, rendering the analysis of the chain computationally demanding and often prohibitive in practice. We here describe how it is possible to efficiently find a smaller, aggregate chain, which preserves certain properties of the original one. Formal methods and lumpability notions are used to define algorithms for automated and efficient construction of such smaller chains (without ever constructing the original ones). We here illustrate the method on an example and we discuss the applicability of the method in the context of modelling large signalling pathways

Syntactic Markovian Bisimulation for Chemical Reaction Networks

In chemical reaction networks (CRNs) with stochastic semantics based on continuous-time Markov chains (CTMCs), the typically large populations of species cause combinatorially large state spaces. This makes the analysis very difficult in practice and represents the major bottleneck for the applicability of minimization techniques based, for instance, on lumpability. In this paper we present syntactic Markovian bisimulation (SMB), a notion of bisimulation developed in the Larsen-Skou style of probabilistic bisimulation, defined over the structure of a CRN rather than over its underlying CTMC. SMB identifies a lumpable partition of the CTMC state space a priori, in the sense that it is an equivalence relation over species implying that two CTMC states are lumpable when they are invariant with respect to the total population of species within the same equivalence class. We develop an efficient partition-refinement algorithm which computes the largest SMB of a CRN in polynomial time in the number of species and reactions. We also provide an algorithm for obtaining a quotient network from an SMB that induces the lumped CTMC directly, thus avoiding the generation of the state space of the original CRN altogether. In practice, we show that SMB allows significant reductions in a number of models from the literature. Finally, we study SMB with respect to the deterministic semantics of CRNs based on ordinary differential equations (ODEs), where each equation gives the time-course evolution of the concentration of a species. SMB implies forward CRN bisimulation, a recently developed behavioral notion of equivalence for the ODE semantics, in an analogous sense: it yields a smaller ODE system that keeps track of the sums of the solutions for equivalent species.Comment: Extended version (with proofs), of the corresponding paper published at KimFest 2017 (http://kimfest.cs.aau.dk/

Is fall prevention by vitamin D mediated by a change in postural or dynamic balance?

Introduction: The objectives were:(1) to validate a quantitative balance assessment method for fall risk prediction; (2) to investigate whether the effect of vitamin D and calcium on the risk of falling is mediated through postural or dynamic balance, as assessed by this method. Materials and methods: A secondary analysis of a double blind randomized controlled trial was employed, which included 64 institutionalized elderly women with complete balance assessment (age range: 65-97; mean 25-hydroxyvitamin D levels: 16.4ng/ml (SD ±9.9). Participants received 1,200mg calcium plus 800IU cholecalciferol (n=33) or 1,200mg calcium (n=31) per day over a 3-month treatment period. Using an electronic device attached to the lower back of the participant, balance was assessed as the degree of trunk angular displacement and angular velocity during a postural task (standing on two legs, eyes open, for 20 s) and a dynamic task (get up from a standard height chair with arm rests, sit down and then stand up again and remain standing). Results: It was found that both postural and dynamic balance independently and significantly predicted the rate of falling within the 3-month follow-up. Vitamin D plus calcium reduced the rate of falls by 60% [relative risk (RR)=0.40; 95% CI: 0.17, 0.94] if compared with calcium alone. Once postural and dynamic balance were added to the regression analysis, they both attenuated the effect of vitamin D plus calcium on the rate of falls. For postural balance, the RR changed by 22% from 0.40 to 0.62 if angular displacement was added to the model, and by 9% from 0.40 to 0.49 if angular velocity was added. For dynamic balance, it changed by 1% from 0.40 to 0.41 if angular displacement was added, and by 14% from 0.40 to 0.54 if angular velocity was added. Discussion: Thus, balance assessment using trunk angular displacement is a valid method for the prediction of falls in older women. Of the observed 60% reduction in the rate of falls by vitamin D plus calcium supplementation compared with calcium alone, up to 22% of the treatment effect was explained by a change in postural balance and up to 14% by dynamic balanc

Neuronal LRP4 regulates synapse formation in the developing CNS

The low-density lipoprotein receptor-related protein 4 (LRP4) is essential in muscle fibers for the establishment of the neuromuscular junction. Here, we show that LRP4 is also expressed by embryonic cortical and hippocampal neurons, and that downregulation of LRP4 in these neurons causes a reduction in density of synapses and number of primary dendrites. Accordingly, overexpression of LRP4 in cultured neurons had the opposite effect inducing more but shorter primary dendrites with an increased number of spines. Transsynaptic tracing mediated by rabies virus revealed a reduced number of neurons presynaptic to the cortical neurons in which LRP4 was knocked down. Moreover, neuron-specific knockdown of LRP4 by in utero electroporation of LRP4 miRNA in vivo also resulted in neurons with fewer primary dendrites and a lower density of spines in the developing cortex and hippocampus. Collectively, our results demonstrate an essential and novel role of neuronal LRP4 in dendritic development and synaptogenesis in the CNS

A cAMP-binding ectoprotein in the yeast Saccharomyces cerevisiae

tides 10, 593-595

An overview of the mid-infrared spectro-interferometer MATISSE: science, concept, and current status

MATISSE is the second-generation mid-infrared spectrograph and imager for the Very Large Telescope Interferometer (VLTI) at Paranal. This new interferometric instrument will allow significant advances by opening new avenues in various fundamental research fields: studying the planet-forming region of disks around young stellar objects, understanding the surface structures and mass loss phenomena affecting evolved stars, and probing the environments of black holes in active galactic nuclei. As a first breakthrough, MATISSE will enlarge the spectral domain of current optical interferometers by offering the L and M bands in addition to the N band. This will open a wide wavelength domain, ranging from 2.8 to 13 um, exploring angular scales as small as 3 mas (L band) / 10 mas (N band). As a second breakthrough, MATISSE will allow mid-infrared imaging - closure-phase aperture-synthesis imaging - with up to four Unit Telescopes (UT) or Auxiliary Telescopes (AT) of the VLTI. Moreover, MATISSE will offer a spectral resolution range from R ~ 30 to R ~ 5000. Here, we present one of the main science objectives, the study of protoplanetary disks, that has driven the instrument design and motivated several VLTI upgrades (GRA4MAT and NAOMI). We introduce the physical concept of MATISSE including a description of the signal on the detectors and an evaluation of the expected performances. We also discuss the current status of the MATISSE instrument, which is entering its testing phase, and the foreseen schedule for the next two years that will lead to the first light at Paranal.Comment: SPIE Astronomical Telescopes and Instrumentation conference, June 2016, 11 pages, 6 Figure