Filter-based stochastic algorithm for global optimization

We propose the general Filter-based Stochastic Algorithm (FbSA) for the global optimization of nonconvex and nonsmooth constrained problems. Under certain conditions on the probability distributions that generate the sample points, almost sure convergence is proved. In order to optimize problems with computationally expensive black-box objective functions, we develop the FbSA-RBF algorithm based on the general FbSA and assisted by Radial Basis Function (RBF) surrogate models to approximate the objective function. At each iteration, the resulting algorithm constructs/updates a surrogate model of the objective function and generates trial points using a dynamic coordinate search strategy similar to the one used in the Dynamically Dimensioned Search method. To identify a promising best trial point, a non-dominance concept based on the values of the surrogate model and the constraint violation at the trial points is used. Theoretical results concerning the sufficient conditions for the almost surely convergence of the algorithm are presented. Preliminary numerical experiments show that the FbSA-RBF is competitive when compared with other known methods in the literature.The authors are grateful to the anonymous referees for their fruitful comments and suggestions.The first and second authors were partially supported by Brazilian Funds through CAPES andCNPq by Grants PDSE 99999.009400/2014-01 and 309303/2017-6. The research of the thirdand fourth authors were partially financed by Portuguese Funds through FCT (Fundação para Ciência e Tecnologia) within the Projects UIDB/00013/2020 and UIDP/00013/2020 of CMAT-UM and UIDB/00319/2020

Adenosyl Radical: Reagent and Catalyst in Enzyme Reactions

Adenosine is undoubtedly an ancient biological molecule that is a component of many enzyme cofactors: ATP, FADH, NAD(P)H, and coenzyme A, to name but a few, and, of course, of RNA. Here we present an overview of the role of adenosine in its most reactive form: as an organic radical formed either by homolytic cleavage of adenosylcobalamin (coenzyme B 12 , AdoCbl) or by single-electron reduction of S -adenosylmethionine (AdoMet) complexed to an iron–sulfur cluster. Although many of the enzymes we discuss are newly discovered, adenosine's role as a radical cofactor most likely arose very early in evolution, before the advent of photosynthesis and the production of molecular oxygen, which rapidly inactivates many radical enzymes. AdoCbl-dependent enzymes appear to be confined to a rather narrow repertoire of rearrangement reactions involving 1,2-hydrogen atom migrations; nevertheless, mechanistic insights gained from studying these enzymes have proved extremely valuable in understanding how enzymes generate and control highly reactive free radical intermediates. In contrast, there has been a recent explosion in the number of radical-AdoMet enzymes discovered that catalyze a remarkably wide range of chemically challenging reactions; here there is much still to learn about their mechanisms. Although all the radical-AdoMet enzymes so far characterized come from anaerobically growing microbes and are very oxygen sensitive, there is tantalizing evidence that some of these enzymes might be active in aerobic organisms including humans.Peer Reviewedhttp://deepblue.lib.umich.edu/bitstream/2027.42/69165/1/604_ftp.pd

A Novel Tool for Studying Auxin-Metabolism: The Inhibition of Grapevine Indole-3-Acetic Acid-Amido Synthetases by a Reaction Intermediate Analogue

An important process for the regulation of auxin levels in plants is the inactivation of indole-3-acetic acid (IAA) by conjugation to amino acids. The conjugation reaction is catalysed by IAA-amido synthetases belonging to the family of GH3 proteins. Genetic approaches to study the biological significance of these enzymes have been hampered by large gene numbers and a high degree of functional redundancy. To overcome these difficulties a chemical approach based on the reaction mechanism of GH3 proteins was employed to design a small molecule inhibitor of IAA-amido synthetase activity. Adenosine-5′-[2-(1H-indol-3-yl)ethyl]phosphate (AIEP) mimics the adenylated intermediate of the IAA-conjugation reaction and was therefore proposed to compete with the binding of MgATP and IAA in the initial stages of catalysis. Two grapevine IAA-amido synthetases with different catalytic properties were chosen to test the inhibitory effects of AIEP in vitro. GH3-1 has previously been implicated in the grape berry ripening process and is restricted to two amino acid substrates, whereas GH3-6 conjugated IAA to 13 amino acids. AIEP is the most potent inhibitor of GH3 enzymes so far described and was shown to be competitive against MgATP and IAA binding to both enzymes with Ki-values 17-68-fold lower than the respective Km-values. AIEP also exhibited in vivo activity in an ex planta test system using young grape berries. Exposure to 5–20 µM of the inhibitor led to decreased levels of the common conjugate IAA-Asp and reduced the accumulation of the corresponding Asp-conjugate upon treatment with a synthetic auxin. AIEP therefore represents a novel chemical probe with which to study IAA-amido synthetase function

Seasonal Propagation Characteristics of MSTIDs Observed at High Latitudes Over Central Alaska Using the Poker Flat Incoherent Scatter Radar

Near‐continuous electron density measurements obtained over a ∼3 year period, 2010–2013, using the Poker Flat Incoherent Scatter Radar (PFISR) in central Alaska (69°N, 147°W) have been analyzed to quantify the properties of over 650 high‐latitude medium‐scale traveling ionospheric disturbances (MSTIDs). Our analysis focused on the altitude range 100–300 km encompassing the lower ionosphere/thermosphere and yielded first full seasonal day/night distributions of MSTIDs at high northern latitudes with mean values: horizontal wavelength 446 km, horizontal phase speed 187 m/s, and period 41 min. These year‐round measurements fill an important summertime gap in existing MSTID measurements revealing predominantly eastward wave propagation during the summer, while continued winter season observations agree well with previous reports of near southward propagating MSTIDs. Our 3 years of results suggest a cyclic change in the seasonal horizontal propagation directions that was found to be quantitatively consistent with critical level wind and dissipative filtering. Concurrent measurements of the vertical wavelength spectrum as a function of altitude also compared favorably in shape with that calculated using a theoretical dispersion relation (Vadas & Fritts, 2005, https://doi.org/10.1029/2004JD005574) for the thermosphere, but with a higher mean value. Evidence supporting the systematic broadening and shrinking in the azimuthal distributions of the MSTIDs during the course of the year was also found, as well as an unexpected correlation between the MSTID propagation directions and the AE index, both of which are under further investigation

A Comprehensive View of Frozen Shoulder: A Mystery Syndrome

Frozen shoulder is a common epidemiological affliction. Data acquired from people who suffer from this type of damage in other joints such as the hip, wrist and ankle also exist; although these syndromes are less common. Treatment for frozen shoulder is primarily physical (physiotherapy, manual therapy), secondary medical (corticosteroid injections) and finally surgical but with limited success. The difficulty in treating this type of condition successfully lies in the lack of knowledge about the risk factors involved and the pathophysiology underlying this mysterious syndrome. This review gives an overview of the current scientific position of frozen shoulder in terms of evolutionary factors, etiology, the different mechanisms of action involved, current treatment options and other possible interventions based on recent discoveries of pathophysiological mechanisms. The overall objective is to clarify several unknown aspects of a syndrome that affects up to 5% of the world's population

Nitric oxide responses in Arabidopsis hypocotyls are mediated by diverse phytohormone pathways

[EN] Plants are often exposed to high levels of nitric oxide (NO) that affects development and stress-triggered responses. However, the way in which plants sense NO is still largely unknown. Here we combine the analysis of early changes in the transcriptome of plants exposed to a short acute pulse of exogenous NO with the identification of transcription factors (TFs) involved in NO sensing. The NO-responsive transcriptome was enriched in hormone homeostasis and signaling-related genes. To assess events involved in NO sensing in hypocotyls, we used a functional sensing assay based on the NO-induced inhibition of hypocotyl elongation in etiolated seedlings. Hormone-related mutants and the TRANSPLANTA collection of transgenic lines conditionally expressing Arabidopsis TFs were screened for NO-triggered hypocotyl shortening. These approaches allowed the identification of hormone-related TFs, ethylene perception and signaling, strigolactone biosynthesis and signaling, and salicylate production and accumulation that are essential for or modulate hypocotyl NO sensing. Moreover, NO inhibits hypocotyl elongation through the positive and negative regulation of some abscisic acid (ABA) receptors and transcripts encoding brassinosteroid signaling components thereby also implicating these hormones in NO sensing.This work was supported by grants BIO2014-56067-P and BIO2017-82945-P from the Spanish Ministry of Economy, Industry and Competitiveness and FEDER funds. We thank the Genomics Unit of the Centro Nacional de Biotecnologia (CNB-CSIC, Madrid, Spain) for microarray processing. We gratefully acknowledged the kind donation of mutant seeds: Roberto Solano and Andrea Chini (CNB, Madrid, Spain) for the jaz and myc mutants; Paul Verslues (Institute of Plant and Microbial Biology, Academia Sinica, Taiwan) for the hai mutants; Javier Agusti, Pablo Tornero, and Pedro Rodriguez (IBMCP, Valencia, Spain) for the max, sid2eds5nahG, and pyr/pyl mutants, respectively; and Hiroaki Fujii (University of Turku, Finland) for the snrk2.3 and 2.9 mutants.Castillo López Del Toro, MC.; Coego Gonzalez, A.; Costa-Broseta, Á.; Leon Ramos, J. (2018). Nitric oxide responses in Arabidopsis hypocotyls are mediated by diverse phytohormone pathways. Journal of Experimental Botany. 69(21):5265-5278. https://doi.org/10.1093/jxb/ery286S52655278692