Designing attractive models via automated identification of chaotic and oscillatory dynamical regimes

Chaos and oscillations continue to capture the interest of both the scientific and public domains. Yet despite the importance of these qualitative features, most attempts at constructing mathematical models of such phenomena have taken an indirect, quantitative approach, for example, by fitting models to a finite number of data points. Here we develop a qualitative inference framework that allows us to both reverse-engineer and design systems exhibiting these and other dynamical behaviours by directly specifying the desired characteristics of the underlying dynamical attractor. This change in perspective from quantitative to qualitative dynamics, provides fundamental and new insights into the properties of dynamical systems

microRNA input into a neural ultradian oscillator controls emergence and timing of alternative cell states.

© 2014 Macmillan Publishers LimitedThis is an open access article that is freely available in ORE or from the publisher's web site. Please cite the published version.Progenitor maintenance, timed differentiation and the potential to enter quiescence are three fundamental processes that underlie the development of any organ system. In the nervous system, progenitor cells show short-period oscillations in the expression of the transcriptional repressor Hes1, while neurons and quiescent progenitors show stable low and high levels of Hes1, respectively. Here we use experimental data to develop a mathematical model of the double-negative interaction between Hes1 and a microRNA, miR-9, with the aim of understanding how cells transition from one state to another. We show that the input of miR-9 into the Hes1 oscillator tunes its oscillatory dynamics, and endows the system with bistability and the ability to measure time to differentiation. Our results suggest that a relatively simple and widespread network of cross-repressive interactions provides a unifying framework for progenitor maintenance, the timing of differentiation and the emergence of alternative cell states.Wellcome Trus

The mechanisms of boronate ester formation and fluorescent turn-on in ortho-aminomethylphenylboronic acids

ortho-Aminomethylphenylboronic acids are used in receptors for carbohydrates and various other compounds containing vicinal diols. The presence of the o-aminomethyl group enhances the affinity towards diols at neutral pH, and the manner in which this group plays this role has been a topic of debate. Further, the aminomethyl group is believed to be involved in the turn-on of the emission properties of appended fluorophores upon diol binding. In this treatise, a uniform picture emerges for the role of this group: it primarily acts as an electron-withdrawing group that lowers the pK(a) of the neighbouring boronic acid thereby facilitating diol binding at neutral pH. The amine appears to play no role in the modulation of the fluorescence of appended fluorophores in the protic-solvent-inserted form of the boronic acid/boronate ester. Instead, fluorescence turn-on can be consistently tied to vibrational-coupled excited-state relaxation (a loose-bolt effect). Overall, this Review unifies and discusses the existing data as of 2019 whilst also highlighting why o-aminomethyl groups are so widely used, and the role they play in carbohydrate sensing using phenylboronic acids

Stochastic loss and gain of symmetric divisions in the C. elegans epidermis perturbs robustness of stem cell number

Biological systems are subject to inherent stochasticity. Nevertheless, development is remarkably robust, ensuring the consistency of key phenotypic traits such as correct cell numbers in a certain tissue. It is currently unclear which genes modulate phenotypic variability, what their relationship is to core components of developmental gene networks, and what is the developmental basis of variable phenotypes. Here, we start addressing these questions using the robust number of Caenorhabditis elegans epidermal stem cells, known as seam cells, as a readout. We employ genetics, cell lineage tracing, and single molecule imaging to show that mutations in lin-22, a Hes-related basic helix-loop-helix (bHLH) transcription factor, increase seam cell number variability. We show that the increase in phenotypic variability is due to stochastic conversion of normally symmetric cell divisions to asymmetric and vice versa during development, which affect the terminal seam cell number in opposing directions. We demonstrate that LIN-22 acts within the epidermal gene network to antagonise the Wnt signalling pathway. However, lin-22 mutants exhibit cell-to-cell variability in Wnt pathway activation, which correlates with and may drive phenotypic variability. Our study demonstrates the feasibility to study phenotypic trait variance in tractable model organisms using unbiased mutagenesis screens

Crystal Structural Analysis of DL-Mandelate Salt of Carvedilol and Its Correlation with Physicochemical Properties

A 1:1 salt of carvedilol (CVD), an anti-hypertensive drug, with DL-mandelic acid (DL-MA) was crystallized from ethanol and the structure was characterized by X-ray single-crystal diffraction, revealing salt formation by transfer of an acidic proton from the COOH group of MA to the aliphatic (acyclic) secondary amino NH group of CVD. The crystal structure is triclinic, with a P-1 space group and unit cell parameters a = 9.8416(5) Å, b = 11.4689(5) Å, c = 14.0746(7) Å, α = 108.595(8), β = 95.182(7), γ = 107.323(8), V = 1406.95(15) Å3, and Z = 2. The asymmetric unit contained one protonated CVD and one MA anion, linked via an N+–H∙∙∙O¯ strong hydrogen bond and a ratio of 1:1. As previously reported, the thermal, spectroscopic, and powder X-ray diffraction properties of the salt of CVD with DL-MA (CVD_DL-MA) differed from CVD alone. The intrinsic dissolution rate of CVD_DL-MA was about 10.7 times faster than CVD alone in a pH 6.8 buffer

Efeito higrotérmico em prepregs de fibra de vidro/epóxi por espectroscopia de luminescência Hygrothermal effect in glass fiber/epoxy by luminescence spectroscopy

O objetivo deste trabalho é o estudo do efeito higrotérmico em pré-impregnados (prepreg) não curados de fibra de vidro-resina epoxídica usando a técnica de espectroscopia eletrônica de luminescência em modo estacionário. O método de fluorescência extrínseca foi empregado utilizando-se a sonda 9- ácido antróico (9-AA), cujo comportamento fotofísico depende fortemente da polaridade do meio. As amostras foram submetidas a umidades relativas de 6 e 84% por meio da utilização de soluções aquosas saturadas de hidróxido de sódio a 34,5 &deg;C e cloreto de potássio a 20,0 &deg;C, em recipientes fechados, pelos períodos de tempo de 1 semana, 15 dias e 1 mês. As amostras submetidas à umidade relativa de 6% apresentaram aumento significativo das intensidades relativas dos espectros de fluorescência em relação à amostra referência. Este comportamento fotofísico foi atribuído à presença da forma protonada do 9-AA no meio devido à reticulação da matriz polimérica. Após 1 mês, o espectro de emissão apresenta uma diminuição da intensidade em seu máximo. Isto ocorreu provavelmente devido ao processo de plastificação da matriz polimérica promovido pela presença de água na matriz, confirmado pela análise gravimétrica. Os espectros de fluorescência extrínseca das amostras submetidas à umidade relativa de 84% apresentaram as seguintes modificações espectrais: a) decaimento da intensidade de emissão das curvas b e d; b) deslocamento da banda de emissão para a região do azul devido ao aumento do teor de água; e c) aparecimento de um ombro na banda de emissão em 424 e 472 nm. Este comportamento fotofísico foi atribuído ao deslocamento do equilíbrio químico da forma protonada para a forma ionizada do 9-AA, promovido pela entrada de umidade no material.<br>The work is aimed at studying hygrothermal effects on uncured glass-epoxy fiber prepreg (F-161 - Hexcel Co.) using luminescence spectroscopy under steady-state conditions. The fluorescence extrinsic method was employed using the 9-anthroic acid probe, whose photophysical behavior is strongly dependent on the polarity of the medium. The samples were submitted to relative humidity of 6 and 84% using saturated aqueous solutions of NaOH at 34.5 &deg;C and KCl at 20.0 &deg;C in closed recipients, for periods of time of 1 week, 15 days and 1 month. The samples submitted to the relative humidity of 6% showed a significant increase in the relative intensity of the fluorescence spectra in relation to the reference sample. This photophysical behavior was attributed to the 9-AA protonated form in the medium due to the polymeric matrix cross-linking process. After 1 month, the emission spectrum showed a decreased maximum intensity, which could be related to the polymeric matrix plasticization caused by water absorption, which was confirmed by gravimetric analysis. The extrinsic fluorescence spectra of the samples submitted to relative humidity of 84% showed the following spectral modifications: a) emission intensity decrease in curves b and d; b) blue shift in the emission band due to the humidity content; e c) appearance of a shoulder in the emission band at 424 and 472 nm. This photophysical behavior was attributed to the chemical equilibrium between protonated and ionized forms of 9-AA in the medium, promoted by absorption of water in the material