Trichoderma Enzymes for Degradation of Aflatoxin B1 and Ochratoxin A

The contamination of agricultural products with mycotoxins causes risks to animal and human health and severe economic losses. Mycotoxicoses can be reduced by preventing fungal infection using chemical and biological approaches. The chemical strategies can release toxic molecules; therefore, strategies for biological control are being evaluated, such as using nontoxic fungi and their metabolites. This work evaluated the effect of exoenzymes produced by the beneficial fungus Trichoderma afroharzianum strain T22 in degrading Aflatoxin B1 (AFB1) and Ochratoxin A (OTA). The ability of Trichoderma to produce hydrolases was stimulated by using different inducing substrates. The highest AFB1 and OTA degradation activity was obtained using a medium containing lyophilized mushrooms and crude fiber. The T. afroharzianum T22’s ability to reduce mycotoxins may be attributed to peroxidase enzymes. This study showed that T. afroharzianum strain T22 or its peroxidase supplementation could represent a sustainable strategy for the degradation of AFB1 and OTA in feed and food products.     

Ultrastructural Damages to H1N1 Influenza Virus Caused by Vapor Essential Oils

Influenza viruses are transmitted from human to human via airborne droplets and can be transferred through contaminated environmental surfaces. Some works have demonstrated the efficacy of essential oils (EOs) as antimicrobial and antiviral agents, but most of them examined the liquid phases, which are generally toxic for oral applications. In our study, we describe the antiviral activity of Citrus bergamia, Melaleuca alternifolia, Illicium verum and Eucalyptus globulus vapor EOs against influenza virus type A. In the vapor phase, C. bergamia and M. alternifolia strongly reduced viral cytopathic effect without exerting any cytotoxicity. The E. globulus vapor EO reduced viral infection by 78% with no cytotoxicity, while I. verum was not effective. Furthermore, we characterized the EOs and their vapor phase by the head-space gas chromatography–mass spectrometry technique, observing that the major component found in each liquid EO is the same one of the corresponding vapor phases, with the exception of M. alternifolia. To deepen the mechanism of action, the morphological integrity of virus particles was checked by negative staining transmission electron microscopy, showing that they interfere with the lipid bilayer of the viral envelope, leading to the decomposition of membranes. We speculated that the most abundant components of the vapor EOs might directly interfere with influenza virus envelope structures or mask viral structures important for early steps of viral infection.     

Drugs Targeting the A3 Adenosine Receptor: Human Clinical Study Data

The A3 adenosine receptor (A3AR) is overexpressed in pathological human cells. Piclidenoson and namodenoson are A3AR agonists with high affinity and selectivity to A3AR. Both induce apoptosis of cancer and inflammatory cells via a molecular mechanism entailing deregulation of the Wnt and the NF-κB signaling pathways. Our company conducted phase I studies showing the safety of these 2 molecules. In the phase II studies in psoriasis patients, piclidenoson was safe and demonstrated efficacy manifested in significant improvements in skin lesions. Namodenoson is currently being developed to treat liver cancer, where prolonged overall survival was observed in patients with advanced liver disease and a Child–Pugh B score of 7. A pivotal phase III study in this patient population has been approved by the FDA and the EMA and is currently underway. Namodenoson is also being developed to treat non-alcoholic steatohepatitis (NASH). A Phase IIa study has been successfully concluded and showed that namodenoson has anti-inflammatory, anti-fibrosis, and anti-steatosis effects. A phase IIb study in NASH is currently enrolling patients. In conclusion, A3AR agonists are promising drug candidates in advanced stages of clinical development and demonstrate safety and efficacy in their targeted indications.     

In Silico Drug Repurposing of FDA-Approved Drugs Highlighting Promacta as a Potential Inhibitor of H7N9 Influenza Virus

Influenza virus infections continue to be a significant and recurrent public health problem. Although vaccine efficacy varies, regular immunisation is the most effective method for suppressing the influenza virus. Antiviral drugs are available for influenza, although two of the four FDA-approved antiviral treatments have resulted in significant drug resistance. Therefore, new treatments are being sought to reduce the burden of flu-related illness. The time-consuming development of treatments for new and re-emerging diseases such as influenza and the high failure rate are increasing concerns. In this context, we used an in silico-based drug repurposing method to repurpose FDA-approved drugs as potential therapies against the H7N9 virus. To find potential inhibitors, a total of 2568 drugs were screened. Promacta, tucatinib, and lurasidone were identified as promising hits in the DrugBank database. According to the calculations of MM-GBSA, tucatinib (−54.11 kcal/mol) and Promacta (−56.20 kcal/mol) occupied the active site of neuraminidase with a higher binding affinity than the standard drug peramivir (−49.09 kcal/mol). Molecular dynamics (MD) simulation studies showed that the C-α atom backbones of the complexes of tucatinib and Promacta neuraminidase were stable throughout the simulation period. According to ADME analysis, the hit compounds have a high gastrointestinal absorption (GI) and do not exhibit properties that allow them to cross the blood–brain barrier (BBB). According to the in silico toxicity prediction, Promacta is not cardiotoxic, while lurasidone and tucatinib show only weak inhibition. Therefore, we propose to test these compounds experimentally against the influenza H7N9 virus. The investigation and validation of these potential H7N9 inhibitors would be beneficial in order to bring these compounds into clinical settings.     

“东方经济”与中国乡村工业化的社会学机制—重访史国衡的个旧矿城研究

本文对“魁阁”社会学家史国衡1940年代在美访学期间的一部未刊稿《个旧矿城》进行了梳理与讨论。史国衡的个旧研究呈现了一个将产业、民情与治理相结合的综合进路,通过对个旧锡业兴衰的个案分析,揭示了传统“东方经济”模式的独特特征以及决定中国乡村工业化成败的社会学机制,同时也以个旧经验对现代化理论、人际关系学派等当时美国社会科学主流范式提出了反思。《个旧矿城》与另一部更为人所熟知的著作《昆厂劳工》共同构成了史国衡关于中国工业化研究的姊妹篇,“工业化的社会基础”是其中一以贯之的核心线索。对史国衡个旧矿城研究的“再发现”,有助于我们重新认识中国早期社会学的工业研究传统,同时也提示我们,当下的乡村工业化乃至乡村振兴仍然需要重视产业的社会基础,处理好经济转型与社会重组之间的辩证关系。     

Autoradiographische Untersuchungen zur Vermisechung von Baustoffkomponenten

Die Feinverteilung des Kalkes im Kalk-Quarzsand-Gemisch ist eine notwendige Bedingung fur hohe erreichbare Festigkeit der Silikatbaustoffe. Vergleiehende Untersuchungen über die Kalkverteilung an neutronenaktivierten feinkörnigen Baustoffproben mit Hilfe von Szintillationsmessungen des ⁴⁷Ca-Gehaltes und mittels autoradiographischer Darstellung der Kalkverteilung in kleinen Prüfkörpern unter Ausnützung der relativ weichen β-Strahlung des ⁴⁵Ca ergaben, daβ die autoradiographischen Aussagen über die Homogenität der Proben am besten mit den Festigkeitsiwerten der Prüfkörper korrespondieren.     

Spectroscopic properties of the photoproducts of pyridoxal-5′-P irradiation: Catalytic site recognition of ribonuclease A

Photoproducts of pyridoxal-5-P, i.e., 4-pyridoxic-5-P and bis-pyridoxal-5-P, have been studied by spectroscopic methods. The spectroscopic properties of bis-pyridoxal-5-P (bis-PLP) resemble those of pyridoxal-5-P (PLP) under similar experimental conditions. The coupling of methylen hydrogens to the phosphorus atom has been shown by NMR spectroscopy. The singlet in the³¹P-NMR spectra and the triplet in¹H-undecoupled experiments confirm the presence of the phosphate group in the 5 position of the structure of the vitamin. The effect of pH and solvent composition on the relative distribution of species of bis-pyridoxine-5-P (bis-PNP) has been investigated by absorption and fluorescence spectroscopy. The acid-base dissociation of the phosphate group is easily detected by emission spectroscopy. Bis-PNP and bis-PLP bind to the enzyme RNase A and they behave as competitive inhibitors with respect to the substrate cytidine-2-3-cyclic phosphate. The natural forms of vitamin B₆, pyridoxine, and pyridoxine-5-P have no effect on the catalytic activity of the protein. Experimental evidence derived from fluorescence and inhibition experiments is consistent with the hypothesis that bis-PNP recognizes the catalytic site of RNase A.     

Variations on the theme of repeated distances

We give an asymptotically sharp estimate for the error term of the maximum number of unit distances determined byn points in ^{d, d}4. We also give asymptotically tight upper bounds on the total number of occurrences of the favourite distances fromn points in ^{d, d}4. Related results are proved for distances determined byn disjoint compact convex sets in ².At the time this paper was written, both authors were visiting the Technion — Israel Institute of Technology.     

Monotone clones and the varieties they determine

A finite, nontrivial algebra is order-primal if its term functions are precisely the monotone functions for some order on the underlying set. We show that the prevariety generated by an order-primal algebra P is relatively congruence-distributive and that the variety generated by P is congruence-distributive if and only if it contains at most two non-ismorphic subdirectly irreducible algebras. We also prove that if the prevarieties generated by order-primal algebras P and Q are equivalent as categories, then the corresponding orders or their duals generate the same order variety. A large class of order-primal algebras is described each member of which generates a variety equivalent as a category to the variety determined by the six-element, bounded ordered set which is not a lattice. These results are proved by considering topological dualities with particular emphasis on the case where there is a monotone near-unanimity function.This research was carried out while the third author held a research fellowship at La Trobe University supported by ARGS grant B85154851. The second author was supported by a grant from the NSERC.     

Cardinal hermite interpolation with box splines II

Summary In the present work we extent the results in [RS] on CHIP, i.e. Cardinal Hermite Interpolation by the span of translates of directional derivatives of a box spline. These directional derivatives are that ones which define the type of the Hermite Interpolation. We admit here several (linearly independent) directions with multiplicities instead of one direction as in [RS]. Under the same assumptions on the smoothness of the box spline and its defining matrixT we can prove as in [RS]: CHIP has a system of fundamental solutions which are inL L ² together with its directional derivatives mentioned above. Moreover, for data sequences inl ^p ( ^d ), 1p2, there is a spline function inL ^p, 1/p+1/p=1, which solves CHIP.Research supported in part by NSERC Canada under Grant # A7687. This research was completed while this author was supported by a grant from the Deutscher Akademischer Austauschdienst