Ergodic Research Articles

Solving a Mystery with Classical and Dual Photoredox Catalysis: Application of Nickel in the Synthesis of Ergot Alkaloids.

A short synthesis of the ergot alkaloid lysergene and a formal total synthesis of lysergic acid diethylamide (LSD) under the avoidance of palladium and including two nickel-catalyzed steps instead have been developed. A key intermediate of this approach has already been reported by Hendrickson et al. in 2004 (Hendrickson, J.B. et al. Org. Lett. 2004, 6, 3-5), yet the spectral data do not match, adding to doubts about the course of their route. While the final steps of the Hendrickson synthesis could not be reproduced, we were able to leverage the elusive intermediate.

An unexpected role of EasDaf: catalyzing the conversion of chanoclavine aldehyde to chanoclavine acid.

Ergot alkaloids (EAs) are a diverse group of indole alkaloids known for their complex structures, significant pharmacological effects, and toxicity to plants. The biosynthesis of these compounds begins with chanoclavine-I aldehyde (CC aldehyde, 2), an important intermediate produced by the enzyme EasDaf or its counterpart FgaDH from chanoclavine-I (CC, 1). However, how CC aldehyde 2 is converted to chanoclavine-I acid (CC acid, 3), first isolated from Ipomoea violacea several decades ago, is still unclear. In this study, we provide in vitro biochemical evidence showing that EasDaf not only converts CC 1 to CC aldehyde 2 but also directly transforms CC 1 into CC acid 3 through two sequential oxidations. Molecular docking and site-directed mutagenesis experiments confirmed the crucial role of two amino acids, Y166 and S153, within the active site, which suggests that Y166 acts as a general base for hydride transfer, while S153 facilitates proton transfer, thereby increasing the acidity of the reaction. KEY POINTS: • EAs possess complicated skeletons and are widely used in several clinical diseases • EasDaf belongs to the short-chain dehydrogenases/reductases (SDRs) and converted CC or CC aldehyde to CC acid • The catalytic mechanism of EasDaf for dehydrogenation was analyzed by molecular docking and site mutations.

High deoxynivalenol and ergot alkaloid levels in wheat grain: effects on growth performance, carcass traits, rumen fermentation, and blood parameters of feedlot cattle.

This study was designed to assess the impacts of a mixture of deoxynivalenol (DON) and ergot alkaloids (EAs) on growth performance, rumen function, blood parameters, and carcass traits of feedlot cattle. Forty steers (450 ± 6.0kg) were stratified by weight and randomly allocated to 1 of 4 treatments; control-low (CON-L), control-high (CON-H) which contained low or high wheat screenings that lacked mycotoxins at the same level as the mycotoxin-low (MYC-L; 5.0mg/kg DON, 2.1mg/kg EA), and mycotoxin-high (MYC-H: 10mg/kg DON, 4.2mg/kg EA) diets that included wheat screening with mycotoxins. Steers were housed in individual pens for a 112-day finishing trial. Intake was 24.8% lower (P < 0.001) for MYC steers compared to CON steers. As a result, average daily gains of MYC steers were 42.1% lower (P < 0.001) than CON steers. Gain to feed ratio was also lower (P < 0.001) for MYC steers compared to CON steers. Platelets, alanine aminotransferase, globulins, and blood urea nitrogen were lower (P ≤ 0.008), and lymphocytes, glutathione peroxidase activity (GPx), and interleukin-10 (IL-10) were elevated (P ≤ 0.002) in MYC steers compared to CON steers. Hot carcass weights and backfat thickness were reduced (P < 0.001) in MYC steers, resulting in leaner (P < 0.001) carcasses and higher (P < 0.007) meat yield compared to CON steers. Results suggest that a mixture of DON and EAs negatively impacted health, performance, and carcass traits of feedlot steers, with the majority of this response likely attributable to EAs. However, more research is needed to distinguish the relative contribution of each mycotoxin to the specific responses observed.

Prediction of dynamical systems from time-delayed measurements with self-intersections

In the context of predicting the behaviour of chaotic systems, Schroer, Sauer, Ott and Yorke conjectured in 1998 that if a dynamical system defined by a smooth diffeomorphism T of a Riemannian manifold X admits an attractor with a natural measure μ of information dimension smaller than k, then k time-delayed measurements of a one-dimensional observable h are generically sufficient for μ-almost sure prediction of future measurements of h. In a previous paper we established this conjecture in the setup of injective Lipschitz transformations T of a compact set X in Euclidean space with an ergodic T-invariant Borel probability measure μ. In this paper we prove the conjecture for all (also non-invertible) Lipschitz systems on compact sets with an arbitrary Borel probability measure, and establish an upper bound for the decay rate of the measure of the set of points where the prediction is subpar. This partially confirms a second conjecture by Schroer, Sauer, Ott and Yorke related to empirical prediction algorithms as well as algorithms estimating the dimension and number of required delayed measurements (the so-called embedding dimension) of an observed system. We also prove general time-delay prediction theorems for locally Lipschitz or Hölder systems on Borel sets in Euclidean space.

All-in-one 2LabsToGo system for analysis of ergot alkaloids in whole rye

Ergot alkaloids, naturally occurring mycotoxins of Claviceps fungi, pose health risks. This necessitates accurate analysis methods to ensure food safety. This study explored the open-source miniaturized all-in-one 2LabsToGo system to analyze ergot alkaloids in whole rye samples. It is suited for sustainable atline analysis as it combines all planar chromatography tasks, allowing low-cost quality control in milling plants. The LOD and LOQ of ergocristine were determined to be 0.4 and 1.2 ng/zone, respectively. Detectability of ergot alkaloids was proven to be below the current maximum limit of 500 µg/kg for rye milling products. The repeatability (%RSD) was 4.1 % and the coefficient of determination of the analytical response (R2) was 0.9918 for ergocristine. The mean recovery rate of ergot alkaloids in spiked whole rye grain was close to 100 %. Results of screening whole rye for ergot alkaloids were successfully verified by comparison with those obtained by conventional status quo HPTLC instrumentation.

Strong Probabilistic Stability in Holomorphic Families of Endomorphisms of ℙk (ℂ) and Polynomial-Like Maps

Abstract We prove that, in stable families of endomorphisms of $\mathbb{P}^{k} (\mathbb C)$, the measurable holomorphic motion of the Julia sets introduced by Berteloot, Dupont, and the first author is unbranched at almost every point with respect to all measures on the Julia set with strictly positive Lyapunov exponents and not charging the post-critical set. This provides a parallel in this setting to the probabilistic stability of Hénon maps by Berger–Dujardin–Lyubich. An analogous result holds in families of polynomial-like maps of large topological degree. In this case, we also give a sufficient condition for the positivity of the Lyapunov exponents of an ergodic measure in terms of its measure-theoretic entropy, generalizing to this setting an analogous result by de Thélin and Dupont valid on $\mathbb{P}^{k} (\mathbb C)$.

First Synthesis of Ergotamine-13CD3 and Ergotaminine-13CD3 from Unlabeled Ergotamine.

Ergot alkaloids (EAs) formed by Claviceps fungi are one of the most common food contaminants worldwide, affecting cereals such as rye, wheat, and barley. To accurately determine the level of contamination and to monitor EAs maximum levels set by the European Union, the six most common EAs (so-called priority EAs) and their corresponding epimers are quantified using high-performance liquid chromatography coupled with tandem mass spectrometry (HPLC-MS/MS). The quantification of EAs in complex food matrices without appropriate internal standards is challenging but currently carried out in the standard method EN 17425:2021 due to their commercial unavailability. To address the need for isotopically labeled EAs, we focus on two semi-synthetic approaches for the synthesis of these reference standards. Therefore, we investigate the feasibility of the N6-demethylation of native ergotamine to yield norergotamine, which can subsequently be remethylated with an isotopically labeled methylating reagent, such as iodomethane (13CD3-I), to yield isotopically labeled ergotamine and its C8-epimer ergotaminine. Testing the isotopically labeled ergotamine/-inine against native ergotamine/-inine with HPLC coupled to high-resolution HR-MS/MS proved the structure of ergotamine-13CD3 and ergotaminine-13CD3. Thus, for the first time, we can describe their synthesis from unlabeled, native ergotamine. Furthermore, this approach is promising as a universal way to synthesize other isotopically labeled EAs.

Tools to make Stachybotrys chartarum genetically amendable: Key to unlocking cryptic biosynthetic gene clusters

The soil and indoor fungus Stachybotrys chartarum can induce respiratory disorders, collectively referred to as stachybotryotoxicosis, owing to its prolific production of diverse bioactive secondary metabolites (SMs) or mycotoxins. Although many of the toxins responsible for the harmful effects on animals and humans have been identified in the genus Stachybotrys, a number of secondary metabolites remain elusive. Through in silico analyses, we have identified 37 polyketide synthase (PKS) genes, highlighting that the chemical profile potential of Stachybotrys is far from being fully explored. Additionally, by leveraging phylogenetic analysis of known SMs produced by non-reducing polyketide synthases (NR-PKS) in other filamentous fungi, we showed that Stachybotrys possesses a rich reservoir of untapped SMs. To unravel natural product biosynthesis in S. chartarum, genetic engineering methods are crucial. For this purpose, we have developed a reliable protocol for the genetic transformation of S. chartarum and applied it to the ScPKS14 gene cluster. This cluster is homologous to the already known Claviceps purpurea CpPKS8 gene cluster, responsible for the production of ergochromes. While no novel SMs were detected, we successfully applied genetic tools, such as generating deletions and overexpressing single cluster genes. This toolbox can now be readily employed to unravel not only this particular biosynthetic gene cluster but also other candidate biosynthetic gene clusters present in S. chartarum, making this fungus accessible for genetic engineering.

Similarities and differences between specification and non-uniform specification

Abstract Pavlov [Adv. Math.295 (2016), 250–270; Nonlinearity32 (2019), 2441–2466] studied the measures of maximal entropy for dynamical systems with weak versions of specification property and found the existence of intrinsic ergodicity would be influenced by the assumptions of the gap functions. Inspired by these, in this article, we study the dynamical systems with non-uniform specification property. We give some basic properties these systems have and give an assumption for the gap functions to ensure the systems have the following five properties: CO-measures are dense in invariant measures; for every non-empty compact connected subset of invariant measures, its saturated set is dense in the total space; ergodic measures are residual in invariant measures; ergodic measures are connected; and entropy-dense. In addition, we will give examples to show the assumption is optimal.

Non-existence of a universal zero-entropy system via generic actions of almost complete growth

Abstract We prove that a generic probability measure-preserving (p.m.p.) action of a countable amenable group G has scaling entropy that cannot be dominated by a given rate of growth. As a corollary, we obtain that there does not exist a topological action of G for which the set of ergodic invariant measures coincides with the set of all ergodic p.m.p. G-systems of entropy zero. We also prove that a generic action of a residually finite amenable group has scaling entropy that cannot be bounded from below by a given sequence. In addition, we show an example of an amenable group that has such a lower bound for every free p.m.p. action.

A platform for predicting mechanism of action based on bacterial transcriptional responses identifies an unusual DNA gyrase inhibitor

In the search for much-needed new antibacterial chemical matter, a myriad of compounds have been reported in academic and pharmaceutical screening endeavors. Only a small fraction of these, however, are characterized with respect to mechanism of action (MOA). Here, we describe a pipeline that categorizes transcriptional responses to antibiotics and provides hypotheses for MOA. 3D-printed imaging hardware PFIboxes) profiles responses of Escherichia coli promoter-GFP fusions to more than 100 antibiotics. Notably, metergoline, a semi-synthetic ergot alkaloid, mimics a DNA replication inhibitor. Invitro supercoiling assays confirm this prediction, and a potent analog thereof (MLEB-1934) inhibits growth at 0.25μg/mL and is highly active against quinolone-resistant strains of methicillin-resistant Staphylococcus aureus. Spontaneous suppressor mutants map to a seldom explored allosteric binding pocket, suggesting a mechanism distinct from DNA gyrase inhibitors used in the clinic. In all, the work highlights the potential of this platform to rapidly assess MOA of new antibacterial compounds.

Shadowing for nonuniformly hyperbolic maps in Hilbert spaces

We prove a shadowing lemma for nonuniformly hyperbolic maps in Hilbert spaces. As applications, we firstly prove that the positive Lyapunov exponents of a hyperbolic ergodic measure µ can be approximated by positive Lyapunov exponents of atomic measures on hyperbolic periodic orbits; secondly, give an upper estimation of metric entropy by using the exponential growth rate of the number of such periodic points that their atomic measures approximate µ and their positive Lyapunov exponents approximate the positive Lyapunov exponents of µ.

Dynamical Analysis of Stochastic Predator-prey Model with Scavenger

In this paper, we studied the dynamic properties of predator-prey and scavenger three species system by using ergodic invariant measures. Pengyu Ma. find the five points of dynamical bifurcation of the stochastic model, which happened between extinction and survival of each species. Environmental noise was added and proved by the fact that driving force produced by environmental noise influence the system and it was find that system may extinct or partially extinct. Here, we have analysed the stochastic bifurcation phenomena of the prey-predator with scavenger system from the nature of dynamic bifurcation. The phase plots and time diagram plotted for the different values of parameters. We have verified all the results by numerical simulations.

Genome wide characterization and expression analysis of CrRLK1L gene family in wheat unravels their roles in development and stress-specific responses.

Catharanthus roseus receptor-like kinase 1-like (CrRLK1L) genes encode a subfamily of receptor-like kinases (RLK) that regulate diverse processes during plant growth, development, and stress responses. The first CrRLK1L was identified from the Catharanthus roseus, commonly known as Madagascar periwinkle. Subsequently, CrRLK1L gene families have been characterized in many plants. The genome of T. aestivum encodes 15 CrRLK1L genes with 43 paralogous copies, with three homeologs each, except for -2-D and -7-A, which are absent. Chromosomal localization analysis revealed a markedly uneven distribution of CrRLK1L genes across seven different chromosomes, with chromosome 4 housing the highest number of genes, while chromosome 6 lacked any CrRLK1L genes. Tissue-specific gene expression analysis revealed distinct expression patterns among the gene family members, with certain members exhibiting increased expression in reproductive tissues. Gene expression analysis in response to various abiotic and biotic stress conditions unveiled differential regulation of gene family members. Cold stress induces CrRLK1Ls -4-B and -15-A while downregulating -3-A and -7B. Drought stress upregulates -9D, contrasting with the downregulation of -7D. CrRLK1L-15-B and -15-D were highly induced in response to 1 hr of heat, and combined drought and heat stress, whereas -10-B is downregulated. Similarly, in response to NaCl stress, only CrRLK1L1 homeologs were induced. Fusarium graminearum and Claviceps purpurea inoculation induces homeologs of CrRLK1L-6 and -7. The analysis of cis-acting elements in the promoter regions identified elements crucial for plant growth and developmental processes. This comprehensive genome-wide analysis and expression study provides valuable insights into the essential functions of CrRLK1L members in wheat.

Ergot Alkaloids in Rye Flour Marketed in Czech Republic: Comparison Between ELISA and LC–MS Methodologies

Ergot Alkaloids in Rye Flour Marketed in Czech Republic: Comparison Between ELISA and LC–MS Methodologies

Measure transfer and S-adic developments for subshifts

Abstract Based on previous work of the authors, to any S-adic development of a subshift X a ‘directive sequence’ of commutative diagrams is associated, which consists at every level $n \geq 0$ of the measure cone and the letter frequency cone of the level subshift $X_n$ associated canonically to the given S-adic development. The issuing rich picture enables one to deduce results about X with unexpected directness. For instance, we exhibit a large class of minimal subshifts with entropy zero that all have infinitely many ergodic probability measures. As a side result, we also exhibit, for any integer $d \geq 2$ , an S-adic development of a minimal, aperiodic, uniquely ergodic subshift X, where all level alphabets $\mathcal A_n$ have cardinality $d,$ while none of the $d-2$ bottom level morphisms is recognizable in its level subshift $X_n \subseteq \mathcal A_n^{\mathbb {Z}}$ .

A Short Synthesis of (−)‐6,7‐Secoagroclavine via Metal‐Free Reductive Coupling

AbstractA concise, convergent, and enantioselective synthesis of (−)‐6,7‐secoagroclavine, a pivotal intermediate in the synthesis of both clavine and ergot alkaloids, was accomplished from a derivative of the renowned Uhle's ketone. The synthesis is centered on metal‐free reductive coupling of the tosylhydrazone derivative of protected 4‐amino Uhle's ketone and commercially available 2,2‐dimethylethenylboronic acid, which is used as a four‐carbon building block. This novel approach directly sets the stereochemistry on the difficult‐to‐access aryl vinyl methane carbon stereogenic center of (−)‐6,7‐secoagroclavine.

165 Does supplementation of beef cattle impact the agronomy performance of tall fescue and bermudagrass pastures?

Abstract In forage-based beef cattle systems, bermudagrass [Cynodon dactylon (L.) Pers.] and tall fescue (Festuca arundinacea Schreb.) stand as widely used forage species. The strategic supplementation of animals may reduce forage intake, thereby potentially affecting the agronomic performance of these grasses. Our objective was to evaluate the impact of beef cattle supplemental feeding on forage accumulation, forage mass, and nutritive value in tall fescue and bermudagrass pastures. Two studies were conducted where pregnant beef cows were supplemental fed 1% of BW on DM basis of corn silage daily (SUP) or received no supplemental feeding (free-choice mineral; NON). Trial 1: conducted on bermudagrass pastures (BERM) grazed from late May to early October. Experimental design for BERM was completely randomized design with 4 pastures per treatment (n = 3 cows/pasture; average 5 years of age; 550 ± 72 kg initial BW). Trial 2: conducted on fescue pastures (FES) with an experimental design of a 2 x 2 factorial arrangement. The two factors evaluated were fescue type [TOXIC (507 ppm ± 0.82 SEM ergot alkaloids; 92.5% endophyte infection)] or non-toxin-producing (NT; 5 ppm ± 2.50 SEM ergot alkaloids; 38.6% endophyte infection) and two levels of supplemental feeding (NON or SUP). There were 3 or 4 replications per fescue x supplemental feeding treatment (n = 15 pastures), stocked with 3 cows/pasture (average age 4.75 years; 558 ± 73 kg initial BW) and grazed from early May through November. Forage accumulation (FA) was estimated every 28 d using the paired-cage method (4 exclosure cages/pasture). On each exclusion period, the forage mass (FM) was estimated both inside and outside the cages through destructive sampling method and samples analyzed for forage quality. Pasture was experimental unit and repeated measures were included in analysis. Bermudagrass FM tended to be increased by 31% with SUP (P = 0.09; 774 kg/ha greater). Forage accumulation tended (P = 0.07) to be affected by feeding method x month. There was greater FA in June for SUP; however, there was greater FA for NON in July. SUP pastures had greater ADF (1% more; P = 0.01) and reduced TDN (1.5%; P &amp;lt; 0.01) than NON. Forage mass tended to be 10% greater for TOXIC pastures (P = 0.09; 409 kg/ha more forage mass). Supplemental feeding on fescue did not impact FM (P = 0.74). Forage accumulation was not impacted by fescue type, feeding method, nor the interaction (P &amp;gt; 0.30). Cows generally do not consume as much toxic fescue, thus more forage is available in pastures and supplemental feeding did not alter forage parameters. However, on a warm-season grass that is growing while supplemental feeding, forage availability was increased and maybe useful as method to increase stocking rates or as mitigation tool during drought.

132 Effects of supplementing corn silage to fall-calving cows grazing tall fescue on cow and calf performance and physiology

Abstract The objective was to test the effect of fescue varieties and supplemental feeding of cows grazing fescue pastures during the growing season on cow and calf performance and physiology. Multiparous and primiparous Angus crossbred cows (n= 45) averaging 151 ± 7 d of gestation at trial initiation, were stratified and assigned to pasture treatment based on estimated calving date and parity. Treatment design was a 2 x 2 factorial with two types of fescue pasture (toxin producing or non-toxin producing) and two levels of supplemental corn silage (non-supplemented or supplemented at 1% of BW DM basis). Each treatment replicate (pasture, n = 3 or 4 pastures per treatment) was stocked with 3 cows. There were seven replicates of non-toxin-producing fescue (5 ppm ± 2.50 SEM ergot alkaloids; 38.6% endophyte infection), and eight replicates of toxin producing K31 fescue pastures (507 ppm ± 0.82 SEM ergot alkaloids; 92.5% endophyte infection). Cows were fed corn silage (38% DM, 7.83% CP DM basis) daily in fenceline bunks and feeding amount was adjusted at weigh dates to maintain 1% of BW DM basis. Cows were weighed on two consecutive days at initiation and upon conclusion of the study after being fed similar diets for 4 d to minimize variation in ruminal fill. Body weight (BW), body condition score (BCS), hair score (HS), hair length (HL), and rump fat (RF) measurements were taken at initiation (the middle of the second trimester), trial mid-point (beginning of third trimester), and approximately 2 wk before estimated parturition. Cows remained on experimental pastures through parturition. Data were analyzed as a mixed model with pasture as experimental unit and cows within pasture as subsamples. Initial cow BW and BCS were 558 ± 11 kg (SEM), and 4.9 ± 0.08 (SEM), respectively. For all measures of interest there were no significant interactions observed (P &amp;gt; 0.16). Supplemental feeding tended (P = 0.07) to increase BW gain and rump fat (P = 0.05) regardless of fescue type. Cows grazing toxic fescue tended (P = 0.12) to have a longer hair coat. Likewise, cows grazing toxic fescue had less change in overall HS (P = 0.02). Supplemental feeding of corn silage to cows at 1% of BW DM basis while grazing fescue did not significantly affect gain differences or reduce visible symptoms typical of fescue toxicosis when grazing during the growing season.

Data-driven discovery of invariant measures

Invariant measures encode the long-time behaviour of a dynamical system. In this work, we propose an optimization-based method to discover invariant measures directly from data gathered from a system. Our method does not require an explicit model for the dynamics and allows one to target specific invariant measures, such as physical and ergodic measures. Moreover, it applies to both deterministic and stochastic dynamics in either continuous or discrete time. We provide convergence results and illustrate the performance of our method on data from the logistic map and a stochastic double-well system, for which invariant measures can be found by other means. We then use our method to approximate the physical measure of the chaotic attractor of the Rössler system, and we extract unstable periodic orbits embedded in this attractor by identifying discrete-time periodic points of a suitably defined Poincaré map. This final example is truly data-driven and shows that our method can significantly outperform previous approaches based on model identification.