Ergodic Research Articles

Simultaneous Determination of Alternaria Toxins, Ergot Alkaloid Epimers, and Other Major Mycotoxins in Various Food Matrices by LC‐MS/MS

Simultaneous Determination of Alternaria Toxins, Ergot Alkaloid Epimers, and Other Major Mycotoxins in Various Food Matrices by LC‐MS/MS

On the multifractal measures and dimensions of image measures on a class of Moran sets

On a Moran set meeting the strong separation requirement, we examine a family of multifractal Hausdorff and packing measures and dimensions in this study. Let φ∗π be the image measure of ergodic Borel probability measure π and measurable function φ. Entropy is used to calculate the formula for the dimension of the multifractal measure of φ∗π. Moreover, some statistical interpretations, on a class of Moran sets, of the dimensions and corresponding geometrical measures are also supported. Finally, a specific illustration of a measure that satisfies the aforementioned criteria is created.

Study of co-occurrence of mycotoxins in cocoa beans in Brazil by liquid chromatography-tandem mass spectrometry (LC-MS/MS)

In this study, 135 samples of cocoa beans collected in the Amazon and Atlantic Forest regions of Brazil were analysed to evaluate the possible co-occurrence of 34 mycotoxins. The results indicate that 42% of the cocoa samples exhibited quantifiable levels for 11 mycotoxins: aflatoxins (AFs) B1, B2 and G1; ochratoxin A; citrinin; cyclopiazonic acid; tenuazonic acid; paxilline; sterigmatocystin; zearalenone and fumonisin B2. Of the samples, 18% exhibited the co-occurrence of up to six mycotoxins. No toxins belonging to the groups of trichothecenes or ergot alkaloids were detected. Contingency analysis of the incidence of mycotoxins did not show significant differences between the two regions evaluated. Seven samples were contaminated with AFs, while only one contained ochratoxin A above 10 μg kg−1. The accuracy of the method was evaluated by proficiency testing for ochratoxin A, where satisfactory Z-scores were obtained.

Lyapunov exponents and hyperbolic periodic orbits for endomorphisms

We show that Lyapunov exponents of hyperbolic ergodic measures of C2-endomorphisms are approximated by the Lyapunov exponents of hyperbolic measures on periodic orbits.

Johnson–Schwartzman gap labelling for ergodic Jacobi matrices

We consider two-sided Jacobi matrices whose coefficients are obtained by continuous sampling along the orbits of a homeomorphism on a compact metric space. Given an ergodic probability measure, we study the topological structure of the associated almost sure spectrum. We establish a gap labelling theorem in the spirit of Johnson and Schwartzman. That is, we show that the constant value the integrated density of states takes in a gap of the spectrum must belong to the countable Schwartzman group of the base dynamics. This result is a natural companion to a recent result of Alkorn and Zhang, which established a Johnson-type theorem for the families of Jacobi matrices in question.

Invariant measures for stochastic conservation laws on the line

We consider a stochastic conservation law on the line with solution-dependent diffusivity, a super-linear, sub-quadratic Hamiltonian, and smooth, spatially-homogeneous kick-type random forcing. We show that this Markov process admits a unique ergodic spatially-homogeneous invariant measure for each mean in a non-explicit unbounded set. This generalises previous work on the stochastic Burgers equation.

Two Satellite Gene Clusters Enhance Ergot Alkaloid Biosynthesis Capacity of Aspergillus leporis.

Ergot alkaloids are fungal specialized metabolites that are important in agriculture and serve as sources of several pharmaceuticals. Aspergillus leporis is a soil saprotroph that possesses two ergot alkaloid biosynthetic gene clusters encoding lysergic acid amide production. We identified two additional, partial biosynthetic gene clusters within the A. leporis genome containing some of the ergot alkaloid synthesis (eas) genes required to make two groups of clavine ergot alkaloids, fumigaclavines and rugulovasines. Clavines possess unique biological properties compared to lysergic acid derivatives. Bioinformatic analyses indicated the fumigaclavine cluster contained functional copies of easA, easG, easD, easM, and easN. Genes resembling easQ and easH, which are required for rugulovasine production, were identified in a separate gene cluster. The pathways encoded by these partial, or satellite, clusters would require intermediates from the previously described lysergic acid amide pathway to synthesize a product. Chemical analyses of A. leporis cultures revealed the presence of fumigaclavine A. However, rugulovasine was only detected in a single sample, prompting a heterologous expression approach to confirm functionality of easQ and easH. An easA knockout strain of Metarhizium brunneum, which accumulates the rugulovasine precursor chanoclavine-I aldehyde, was chosen as expression host. Strains of M. brunneum expressing easQ and easH from A. leporis accumulated rugulovasine as demonstrated through mass spectrometry analysis. These data indicate that A. leporis is exceptional among fungi in having the capacity to synthesize products from three branches of the ergot alkaloid pathway and for utilizing an unusual satellite cluster approach to achieve that outcome. IMPORTANCE Ergot alkaloids are chemicals produced by several species of fungi and are notable for their impacts on agriculture and medicine. The ability to make ergot alkaloids is typically encoded by a clustered set of genes that are physically adjacent on a chromosome. Different ergot alkaloid classes are formed via branching of a complex pathway that begins with a core set of the same five genes. Most ergot alkaloid-producing fungi have a single cluster of genes that is complete, or self-sufficient, and produce ergot alkaloids from one or occasionally two branches from that single cluster. Our data show that Aspergillus leporis is exceptional in having the genetic capacity to make products from three pathway branches. Moreover, it uses a satellite cluster approach, in which gene products of partial clusters rely on supplementation with a chemical intermediate produced via another gene cluster, to diversify its biosynthetic potential without duplicating all the steps.

Neurophysiological and Vascular Mechanisms of Action of the Serotoninergic Drugs for Abortive Migraine Treatment

Abstract—Migraine is a form of primary headache that affects at least 10% of the world’s population. In addition to recommendations for modifying the patient’s lifestyle, migraine management involves stopping an attack that’s already occurred and/or preventing its occurrence. In the abortive treatment of this cephalalgia, both non-specific (eg, non-opioid analgesics) and specific pharmacological agents, can be used. The latter include, in particular, serotonergic drugs of the classes of triptans (selective 5-HT1B/1D receptor agonists), ditans (selective 5-HT1F-mimetics), and ergot alkaloids (non-selective modulators of various 5-HT receptor subtypes). The review discusses the currently availably results of numerous basic and applied studies of these drug groups, in which the neuronal and vascular components of their antimigraine pharmacodynamics were identified. A significant part of the information was obtained in vivo on the various experimental models of migraine based on the trigeminovascular theory of its pathogenesis. Other data are the results of ex vivo studies on isolated tissues and cell cultures. When analyzing these experimental results, evidence is provided in favor of similar mechanisms for realizing the antimigraine potential of all representatives belonging to the pharmacological classes listed, the neurotropic activity of which prevails over their direct intervention in vascular tone. At the same time, special attention is paid to the controversial and debatable issues in this area, the successful solution of which is a key to further progress in the pharmacotherapy of migraine.

Zavegepant: a promising intranasal medication for migraine treatment

Migraine is the third most prevalent and seventh-highest specific cause of disability worldwide1. It is a neurobiological headache disorder that is caused by increased excitability of the central nervous system. This multifactorial ailment has various causes, including lack of sleep, hormonal imbalance, menstrual cycle, and emotional stress. Some individuals may even trigger migraine due to their choice of food, especially chocolate, milk, caffeine, cheese, and alcoholic beverages2. The variability seen in its clinical presentation includes the pattern of associated symptoms and pain intensity along with photophobia, osmophobia, phonophobia, vomiting, nausea, and movement sensitivity3. Considering the acute onset of this excruciating pain, patients demand rapid relief and the cure of all associated symptoms. Several medications have been introduced. However, nowadays, 5HT1B/1D receptor agonists (sumatriptan, zolmitriptan) and ergot alkaloids (dihydroergotamine mesylate) are being used as intranasal or parenteral medications for the immediate treatment of migraines. Many patients prefer intranasal medications over injectable ones because of their rapid action4. Triptans, one of the most effective treatment regimens for migraine, is unfortunately ineffective intranasally. Moreover, its contraindication for cardiovascular patients restricts its use in almost 10% of the migraine population. On the other hand, dihydroergotamine which is still less effective than triptans, the nasal spray is contraindicated in patients with uncontrolled hypertension, ischemic heart disease, and coronary artery vasospasm5. Co-administration with potent cytochrome P450 3A4 inhibitors may also result in potentially fatal peripheral and cerebral ischemia. Recent studies led to the discovery of novel modulators, like calcitonin gene-related peptide (CGRP), that are crucially implicated in the development and chronicity of migraine. This led to new medications known as gepants that can antagonize the CGRP receptor. Successive advances led to the introduction of first-generation and second-generation gepants. However, both were short-lived due to poor oral bioavailability6, associated liver injury, and less effectiveness, respectively. Zavegepant is the third generation but the first intranasally administered gepant. It is a high-affinity antagonist of the CGRP receptor, has adequate oral bioavailability, and, unlike triptans, does not induce active contraction of coronary arteries; therefore, it is safe for patients with cardiovascular comorbidities. Compared with the prior lead, the pharmacophore of zavegepant has a 2-quinolone and a 7-methylindazole, increasing oxidation stability and nasal irritancy potential while maintaining picomolar receptor binding potency7. In addition to that, it is also 10,000 times more selective for the CGRP receptor than for its counterpart, the amylin receptor8. It was FDA-approved in February 2020 for acute treatment, and results demonstrate that it is safe regarding hepatotoxicity9. Recently it cleared the phase 2 trials and now advancing to phase 3 ones. Zavegepant has a tmax of 15–20 minutes as it provides considerable efficacy over 48 hours, with ultra-rapid pain relief starting 15 minutes after a single therapeutic dose (P=0.0015), prolonged and persistent pain freedom for 2–24 hours and 2–48 hours, respectively, along with sustained pain relief for 2–24 hours10. This makes it highly potent and the safest in terms of side effects. Although the provided data gives ample proof that zavegepant is a revolutionary drug to combat migraine attacks but for definite, high-quality evidence about its efficacy and safety, results from the recent clinical trials and future research work are needed. Similarly, soft gel formulations of zavegepant also need more attention as it can be another option for the abortive treatment of migraine. Lastly, extensive trials are needed to see its effect on pregnant women and patients with severe liver and cardiovascular issues. For commercialization, it should be economically friendly so that it can compete with all the available formulas and a maximum number of patients can be benefitted from it. Rest assured. This third-generation gepant can be a promising medication in terms of timely relief from escalating pain, and further research may even help us find the ultimate cure for migraine. Ethical approval Not applicable. Sources of funding None. Author contribution The conceptualization was done by A.S. and B.S.R. The literature and drafting of the manuscript were conducted by A.S., T.N., A.W.K., S.D.E.Z.Z., A.Q. and H.S.R. The editing and supervision were performed by B.S.R. All authors have read and agreed to the final version of the manuscript. Conflicts of interest disclosure The authors declare that they have no financial conflict of interest with regard to the content of this report. Research registration unique identifying number (UIN) Not applicable. Guarantor All authors take responsibility for the work, access to data and decision to publish.

Evaluation of Trichoderma isolates as biocontrol measure against Claviceps purpurea

Claviceps purpurea causes ergot, a floral disease of major cereal crops, such as winter rye and winter triticale. The dark sclerotia formed by C. purpurea contain numerous toxic ergot alkaloids, which pose a major health risk for humans and animals when ingested. The countermeasures against ergot infection are currently limited to intensive tillage, seed cleaning, crop rotation or integration of optical sorting machines to remove ergot from cereals before processing. However, these practices confer only a minor protective effect and are highly energy-demanding. Thus, more effective and sustainable plant protection measures to combat ergot infections in cereals are needed. The application of Trichoderma spp. as biological control agent has already proven successful against a wide range of phytopathogenic fungi. However, there is only minor scientific evidence about its protective capacity against C. purpurea in cereal crops. In our study, we therefore investigated the antagonistic potential of several Trichoderma isolates against C. purpurea and their ability to confer protection against ergot infection. In initial in vitro tests and confrontation assays, we quantified and compared the production of iron-chelating compounds and hydrolytic enzymes as well as the antagonistic activity against C. purpurea sclerotia and mycelial cultures. Several strains showed high antifungal capacity and growth inhibitory effects towards C. purpurea. Selected Trichoderma strains were then tested for their potential to protect rye (Secale cereale) plants from ergot infection within a greenhouse trial. Rhizosphere-inoculated plants displayed a decreased disease severity compared to plants that had been sprayed with Trichoderma spores above-ground. Gene expression analysis by reverse transcription quantitative PCR also indicated the induction of systemic defense reactions. Overall, our data suggest that individual Trichoderma isolates possess a high antagonistic potential towards C. purpurea, which could be effective by direct mycoparasitism and by inducing systemic plant resistance, and therefore provide important guidance towards the development of Trichoderma treatments of cereals as biocontrol measure against ergot.Graphical abstract

Ergodic Measure and Potential Control of Anomalous Diffusion.

In statistical mechanics, the ergodic hypothesis (i.e., the long-time average is the same as the ensemble average) accompanying anomalous diffusion has become a continuous topic of research, being closely related to irreversibility and increasing entropy. While measurement time is finite for a given process, the time average of an observable quantity might be a random variable, whose distribution width narrows with time, and one wonders how long it takes for the convergence rate to become a constant. This is also the premise of ergodic establishment, because the ensemble average is always equal to the constant. We focus on the time-dependent fluctuation width for the time average of both the velocity and kinetic energy of a force-free particle described by the generalized Langevin equation, where the stationary velocity autocorrelation function is considered. Subsequently, the shortest time scale can be estimated for a system transferring from a stationary state to an effective ergodic state. Moreover, a logarithmic spatial potential is used to modulate the processes associated with free ballistic diffusion and the control of diffusion, as well as the minimal realization of the whole power-law regime. The results presented suggest that non-ergodicity mimics the sparseness of the medium and reveals the unique role of logarithmic potential in modulating diffusion behavior.

Photoredox catalysis enabling decarboxylative radical cyclization of γ,γ-dimethylallyltryptophan (DMAT) derivatives: formal synthesis of 6,7-secoagroclavine.

An unusual photoredox-catalyzed radical decarboxylative cyclization cascade reaction of γ,γ-dimethylallyltryptophan (DMAT) derivatives containing unactivated alkene moieties has been developed, providing green and efficient access to various six-, seven-, and eight-membered ring 3,4-fused tricyclic indoles. This type of cyclization, which was hitherto very difficult to comprehend in ergot biosynthesis and to accomplish by more conventional procedures, enables the synthesis of ergot alkaloid precursors. In addition, this work describes a mild, environmentally friendly method to activate, reductively and oxidatively, natural carboxylic acids for decarboxylative C-C bond formation by exploiting the same photocatalyst.

On arithmetic functions orthogonal to deterministic sequences

We prove the equivalence of Sarnak's conjecture on Möbius orthogonality with a Kolmogorov type property conjectured by Veech for Furstenberg systems of the Möbius function. This yields a combinatorial condition on the Möbius function itself which is equivalent to Sarnak's conjecture. As a matter of fact, our arguments remain valid in a larger context: we characterize all bounded arithmetic functions orthogonal to all topological systems whose all ergodic measures yield systems from a fixed characteristic class (zero entropy class is an example of such a characteristic class) with the characterization persisting in the logarithmic setup. As a corollary, we obtain that the logarithmic Sarnak's conjecture holds if and only if the logarithmic Möbius orthogonality is satisfied for all dynamical systems whose ergodic measures yield nilsystems.

Hyperbolicity of maximal entropy measures for certain maps isotopic to Anosov diffeomorphisms

We prove the hyperbolicity of ergodic maximal entropy measures for a class of partially hyperbolic diffeomorphisms of Td, which have a compact two-dimensional center foliation.

Topological chaos and statistical triviality

While transferring one flow ϕ with fixed points homeomorphically to its equivalent flow ψ, we show that positive topological entropy degenerates to zero (such degeneracy happens for equivalent continuous flows [3] and equivalent differential flows [6]) if and only if all ergodic invariant measures with positive measure-theoretic entropy degenerate to fixed points. Whenever ϕ is assumed to be topological transitive, the measure degeneracy implies that the resulted equivalent flow ψ is topologically chaotic but statistically trivial, meaning that all ergodic invariant measures are supported on fixed points. Using different approaches in different areas people constructed examples of topological chaotic but statistical trivial systems, see [3] for C0 flows, see [6] for Cr, r≥1, flows, see [1][11] for C0 homeomorphisms, see time one map in [6] for Cr, r≥1 diffeomorphisms. We point out it is non-hyperbolic singularity causes the degeneracy while changing one flow equivalently to another.

Nonhyperbolic dynamics by mingling, blending, and flip-flopping

Our aim is to describe the “amount of nonhyperbolicity” either on an orbit-wise level or on a measure-wise one. This is done in the simplest setting of step skew products defined over a shift and with circle fiber maps, which provides a convenient model for partially hyperbolic diffeomorphisms with one-dimensional central bundle. Starting point is topologically transitive systems which display coexisting regions with different type of hyperbolicity. Transitivity forces an interaction between these regions and the emergence of nonhyperbolicity.We review three, closely related, main mechanisms to construct nonhyperbolic ergodic measures. One main approach is to ergodically approximate nonhyperbolicity by hyperbolicity.

Ergot Alkaloids Contribute to the Pathogenic Potential of the Fungus Aspergillus leporis.

Opportunistically pathogenic fungi have varying potential to cause disease in animals. Factors contributing to their virulence include specialized metabolites, which in some cases evolved in contexts unrelated to pathogenesis. Specialized metabolites that increase fungal virulence in the model insect Galleria mellonella include the ergot alkaloids fumigaclavine C in Aspergillus fumigatus (syn. Neosartorya fumigata) and lysergic acid α-hydroxyethylamide (LAH) in the entomopathogen Metarhizium brunneum. Three species of Aspergillus recently found to accumulate high concentrations of LAH were investigated for their pathogenic potential in G. mellonella. Aspergillus leporis was most virulent, A. hancockii was intermediate, and A. homomorphus had very little pathogenic potential. Aspergillus leporis and A. hancockii emerged from and sporulated on dead insects, thus completing their asexual life cycles. Inoculation by injection resulted in more lethal infections than did topical inoculation, indicating that A. leporis and A. hancockii were preadapted for insect pathogenesis but lacked an effective means to breach the insect's cuticle. All three species accumulated LAH in infected insects, with A. leporis accumulating the most. Concentrations of LAH in A. leporis were similar to those observed in the entomopathogen M. brunneum. LAH was eliminated from A. leporis through a CRISPR/Cas9-based gene knockout, and the resulting strain had reduced virulence to G. mellonella. The data indicate that A. leporis and A. hancockii have considerable pathogenic potential and that LAH increases the virulence of A. leporis. IMPORTANCE Certain environmental fungi infect animals occasionally or conditionally, whereas others do not. Factors that affect the virulence of these opportunistically pathogenic fungi may have originally evolved to fill some other role for the fungus in its primary environmental niche. Among the factors that may improve the virulence of opportunistic fungi are specialized metabolites--chemicals that are not essential for basic life functions but provide producers with an advantage in particular environments or under specific conditions. Ergot alkaloids are a large family of fungal specialized metabolites that contaminate crops in agriculture and serve as the foundations of numerous pharmaceuticals. Our results show that two ergot alkaloid-producing fungi that were not previously known to be opportunistic pathogens can infect a model insect and that, in at least one of the species, an ergot alkaloid increases the virulence of the fungus.

Ergodicity for three-dimensional stochastic Navier–Stokes equations with Markovian switching

Asymptotic behavior of the three-dimensional stochastic Navier-Stokes equations with Markovian switching for additive noises is studied for an incompressible fluid flow in a bounded domain. The objective of this article is to prove the existence and identification of a stationary measure for such stochastic systems. To achieve this goal, a family of regularized equations is introduced in order to investigate the asymptotic behavior of their solutions. The existence of an ergodic measure for the regularized system is established by the Krylov-Bogolyubov method. The existence and identification of a stationary measure corresponding to the original system are obtained as a sequential limit point of the family of the ergodic measures that correspond to the regularized systems. The main result of this work is that under mild integrability conditions on the initial data and external force, there exists a stationary measure for the solution of the three-dimensional stochastic Navier-Stokes equations with Markovian switching.

Inoculation and Screening Methods for Major Sorghum Diseases Caused by Fungal Pathogens: Claviceps africana, Colletotrichum sublineola, Sporisorium reilianum, Peronosclerospora sorghi and Macrophomina phaseolina.

Sorghum is the fifth most important crop globally. Researching interactions between sorghum and fungal pathogens is essential to further elucidate plant defense mechanisms to biotic stress, which allows breeders to employ genetic resistance to disease. A variety of creative and useful inoculation and screening methods have been developed by sorghum pathologists to study major fungal diseases. As inoculation and screening methods can be keys for successfully conducting experiments, it is necessary to summarize the techniques developed by this research community. Among many fungal pathogens of sorghum, here we summarize inoculation and screening methods for five important fungal pathogens of sorghum: Claviceps africana, Colletotrichum sublineola, Sporisorium reilianum, Peronosclerospora sorghi and Macrophomina phaseolina. The methods described within will be useful for researchers who are interested in exploring sorghum-fungal pathogen interactions. Finally, we discuss the latest biotechnologies and methods for studying plant-fungal pathogen interactions and their applicability to sorghum pathology.

90 Exposure to Endophyte-Infected Tall Fescue Negatively Impacts Pulmonary Arterial Pressure in Beef Cattle

Abstract Fescue toxicosis negatively impacts cattle productivity. Previous data from our laboratory has demonstrated that cattle within a herd respond differently when grazing tall fescue, thus variation within a breed may provide genetic tolerance to the negative effects on performance. Fescue toxicosis results in major impacts on the cardiovascular system, thus it was hypothesized that exposure to ergot alkaloids negatively impacts pulmonary arterial pressure (PAP). The objective of this study was to examine changes in PAP and other production parameters in cattle consuming endophyte-infected tall fescue. Pregnant Angus cows (2 to 4 years; n = 65) were randomly divided to graze either endophyte-infected (EI) or novel endophyte (EN) pastures for4 consecutive weeks starting in April. Weekly measurements were collected to monitor physiological responses to consuming endophyte-infected tall fescue. In addition, PAP was measured every 4 weeks. Data were analyzed using a MIXED procedure of SAS, and statistical significance was determined at P < 0.05 and a tendency at 0.05 < P < 0.10, and evaluated the effects of treatment, age, week, and its interactions on BW, ADG, BCS, HCS, HSS and PAP. Exposure to EI did not affect BW, ADG, or BCS (P >0.05). Whereas, hair coat scores (1-5 scale) were significantly less for cattle consuming EN pastures (2.15 ± 0.05) compared with consuming EI pastures (2.31 ± 0.05; P < 0.05). Additionally, shedding scores (1-5 scale) were reduced in cattle consuming EN pastures (2.3±0.05) compared with consuming EI pastures (2.5±0.05; P< 0.05). There was a significant difference in PAP measurements in cattle exposed to EN pastures (37.16 ± 0.59 mm Hg) compared with EI pastures (31.31 ± 0.56 mm Hg; P < 0.0001). Additionally, PAP scores tended to deviate over the 14-week study between treatment groups (P = 0.0677). As expected, exposure to EI tall fescue resulted in greater HCS and HSS. However, the decrease in PAP in cattle consuming EI fescue was unexpected. Thus, further investigations are needed to examine the interaction between ergot alkaloid exposure on cardiovascular parameters such as PAP to potentially predict genetic differences in beef cattle to identify animals that would have a lower risk of developing fescue toxicosis.