Bioactivity and structural properties of chimeric analogs of the starfish SALMFamide neuropeptides S1 and S2

The starfish SALMFamide neuropeptides S1 (GFNSALMFamide) and S2 (SGPYSFNSGLTFamide) are the prototypical members of a family of neuropeptides that act as muscle relaxants in echinoderms. Comparison of the bioactivity of S1 and S2 as muscle relaxants has revealed that S2 is ten times more potent than S1. Here we investigated a structural basis for this difference in potency by comparing the bioactivity and solution conformations (using NMR and CD spectroscopy) of S1 and S2 with three chimeric analogs of these peptides. A peptide comprising S1 with the addition of S2's N-terminal tetrapeptide (Long S1 or LS1; SGPYGFNSALMFamide) was not significantly different to S1 in its bioactivity and did not exhibit concentration-dependent structuring seen with S2. An analog of S1with its penultimate residue substituted from S2 (S1(T); GFNSALTFamide) exhibited S1-like bioactivity and structure. However, an analog of S2 with its penultimate residue substituted from S1 (S2(M); SGPYSFNSGLMFamide) exhibited loss of S2-type bioactivity and structural properties. Collectively, our data indicate that the C-terminal regions of S1 and S2 are the key determinants of their differing bioactivity. However, the N-terminal region of S2 may influence its bioactivity by conferring structural stability in solution. Thus, analysis of chimeric SALMFamides has revealed how neuropeptide bioactivity is determined by a complex interplay of sequence and conformation

Structural analysis of the starfish SALMFamide neuropeptides S1 and S2: The N-terminal region of S2 facilitates self-association

The neuropeptides S1 (GFNSALMFamide) and S2 (SGPYSFNSGLTFamide), which share sequence similarity, were discovered in the starfish Asterias rubens and are prototypical members of the SALMFamide family of neuropeptides in echinoderms. SALMFamide neuropeptides act as muscle relaxants and both S1 and S2 cause relaxation of cardiac stomach and tube foot preparations in vitro but S2 is an order of magnitude more potent than S1. Here we investigated a structural basis for this difference in potency using spectroscopic techniques. Circular dichroism spectroscopy showed that S1 does not have a defined structure in aqueous solution and this was supported by 2D nuclear magnetic resonance experiments. In contrast, we found that S2 has a well-defined conformation in aqueous solution. However, the conformation of S2 was concentration dependent, with increasing concentration inducing a transition from an unstructured to a structured conformation. Interestingly, this property of S2 was not observed in an N-terminally truncated analogue of S2 (short S2 or SS2; SFNSGLTFamide). Collectively, the data obtained indicate that the N-terminal region of S2 facilitates peptide self-association at high concentrations, which may have relevance to the biosynthesis and/or bioactivity of S2 in vivo

On the Origin of Traveling Pulses in Bistable Systems

The interaction between a pair of Bloch fronts forming a traveling domain in a bistable medium is studied. A parameter range beyond the nonequilibrium Ising-Bloch bifurcation is found where traveling domains collapse. Only beyond a second threshold the repulsive front interactions become strong enough to balance attractive interactions and asymmetries in front speeds, and form stable traveling pulses. The analysis is carried out for the forced complex Ginzburg-Landau equation. Similar qualitative behavior is found in the bistable FitzHugh-Nagumo model.Comment: 5 pages, RevTeX. Aric Hagberg: http://t7.lanl.gov/People/Aric/; Ehud Meron:http://www.bgu.ac.il/BIDR/research/staff/meron.htm

Poincare' normal forms and simple compact Lie groups

We classify the possible behaviour of Poincar\'e-Dulac normal forms for dynamical systems in $R^n$ with nonvanishing linear part and which are equivariant under (the fundamental representation of) all the simple compact Lie algebras and thus the corresponding simple compact Lie groups. The ``renormalized forms'' (in the sense of previous work by the author) of these systems is also discussed; in this way we are able to simplify the classification and moreover to analyze systems with zero linear part. We also briefly discuss the convergence of the normalizing transformations.Comment: 17 pages; minor corrections in revised versio

Frozen spatial chaos induced by boundaries

We show that rather simple but non-trivial boundary conditions could induce the appearance of spatial chaos (that is stationary, stable, but spatially disordered configurations) in extended dynamical systems with very simple dynamics. We exemplify the phenomenon with a nonlinear reaction-diffusion equation in a two-dimensional undulated domain. Concepts from the theory of dynamical systems, and a transverse-single-mode approximation are used to describe the spatially chaotic structures.Comment: 9 pages, 6 figures, submitted for publication; for related work visit http://www.imedea.uib.es/~victo

Frequency Locking in Spatially Extended Systems

A variant of the complex Ginzburg-Landau equation is used to investigate the frequency locking phenomena in spatially extended systems. With appropriate parameter values, a variety of frequency-locked patterns including flats, $\pi$ fronts, labyrinths and $2\pi/3$ fronts emerge. We show that in spatially extended systems, frequency locking can be enhanced or suppressed by diffusive coupling. Novel patterns such as chaotically bursting domains and target patterns are also observed during the transition to locking

A Novel, Contactless, Portable “Spot-Check” Device Accurately Measures Respiratory Rate

Respiratory rate (RR) is an important vital sign used in the assessment of acutely ill patients. It is also used as to predict serious deterioration in a patient's clinical condition. Convenient electronic devices exist for measurement of pulse, blood pressure, oxygen saturation and temperature. Although devices which measure RR exist, none has entered everyday clinical practice. We developed a contactless portable respiratory rate monitor (CPRM) and evaluated the agreement in respiratory rate measurements between existing methods and our new device. The CPRM uses thermal anemometry to measure breath signals during inspiration and expiration. RR data were collected from 52 healthy adult volunteers using respiratory inductance plethysmography (RIP) bands (established contact method), visual counting of chest movements (established non-contact method) and the CPRM (new method), simultaneously. Two differently shaped funnel attachments were evaluated for each volunteer. Data showed good agreement between measurements from the CPRM and the gold standard RIP, with intra-class correlation coefficient (ICC): 0.836, mean difference 0.46 and 95% limits of agreement of -5.90 to 6.83. When separate air inlet funnels of the CPRM were analysed, stronger agreement was seen with an elliptical air inlet; ICC 0.908, mean difference 0.37 with 95% limits of agreement -4.35 to 5.08. A contactless device for accurately and quickly measuring respiratory rate will be an important triage tool in the clinical assessment of patients. More testing is needed to explore the reasons for outlying measurements and to evaluate in the clinical setting

Order Parameter Equations for Front Transitions: Planar and Circular Fronts

Near a parity breaking front bifurcation, small perturbations may reverse the propagation direction of fronts. Often this results in nonsteady asymptotic motion such as breathing and domain breakup. Exploiting the time scale differences of an activator-inhibitor model and the proximity to the front bifurcation, we derive equations of motion for planar and circular fronts. The equations involve a translational degree of freedom and an order parameter describing transitions between left and right propagating fronts. Perturbations, such as a space dependent advective field or uniform curvature (axisymmetric spots), couple these two degrees of freedom. In both cases this leads to a transition from stationary to oscillating fronts as the parity breaking bifurcation is approached. For axisymmetric spots, two additional dynamic behaviors are found: rebound and collapse.Comment: 9 pages. Aric Hagberg: http://t7.lanl.gov/People/Aric/; Ehud Meron: http://www.bgu.ac.il/BIDR/research/staff/meron.htm

Four-phase patterns in forced oscillatory systems

We investigate pattern formation in self-oscillating systems forced by an external periodic perturbation. Experimental observations and numerical studies of reaction-diffusion systems and an analysis of an amplitude equation are presented. The oscillations in each of these systems entrain to rational multiples of the perturbation frequency for certain values of the forcing frequency and amplitude. We focus on the subharmonic resonant case where the system locks at one fourth the driving frequency, and four-phase rotating spiral patterns are observed at low forcing amplitudes. The spiral patterns are studied using an amplitude equation for periodically forced oscillating systems. The analysis predicts a bifurcation (with increasing forcing) from rotating four-phase spirals to standing two-phase patterns. This bifurcation is also found in periodically forced reaction-diffusion equations, the FitzHugh-Nagumo and Brusselator models, even far from the onset of oscillations where the amplitude equation analysis is not strictly valid. In a Belousov-Zhabotinsky chemical system periodically forced with light we also observe four-phase rotating spiral wave patterns. However, we have not observed the transition to standing two-phase patterns, possibly because with increasing light intensity the reaction kinetics become excitable rather than oscillatory.Comment: 11 page