Plant rhizosphere specificity and variability in the insect and plant adhesins, Madl and Mad2, within the genus Metarhizium suggest plant adaptation as an evolutionary force

Metarhizium is a soil-inhabiting fungus currently used as a biological control agent against various insect species, and research efforts are typically focused on its ability to kill insects. In section 1, we tested the hypothesis that species of Metarhizium are not randomly distributed in soils but show plant rhizosphere-specific associations. Results indicated an association of three Metarhizium species (Metarhizium robertsii, M. brunneum and M. guizhouense) with the rhizosphere of certain types of plant species. M. robertsii was the only species that was found associated with grass roots, suggesting a possible exclusion of M. brunneum and M. guizhouense, which was supported by in vitro experiments with grass root exudate. M. guizhouense and M. brunneum only associated with wildflower rhizosphere when co-occurring with M. robertsii. With the exception of these co-occurrences, M. guizhouense was found to associate exclusively with the rhizosphere of tree species, while M. brunneum was found to associate exclusively with the rhizosphere of shrubs and trees. These associations demonstrate that different species of Metarhizium associate with specific plant types. In section 2, we explored the variation in the insect adhesin, Madl, and the plant adhesin, Mad2, in fourteen isolates of Metarhizium representing seven different species. Analysis of the transcriptional elements within the Mad2 promoter region revealed variable STRE, PDS, degenerative TATA box, and TATA box-like regions. Phylogenetic analysis of 5' EF-Ia, which is used for species identification, as well as Madl and Mad2 sequences demonstrated that the Mad2 phylogeny is more congruent with 5' EF-1a than Madl. This suggests Mad2 has diverged among Metarhizium lineages, contributing to clade- and species-specific variation. While other abiotic and biotic factors cannot be excluded in contributing to divergence, it appears that plant associations have been the driving factor causing divergence among Metarhizium species

Semisynthetic Aurones Inhibit Tubulin Polymerization at the Colchicine-Binding Site and Repress PC-3 Tumor Xenografts in Nude Mice and Myc-Induced T-ALL in Zebrafish

Structure-activity relationships (SAR) in the aurone pharmacophore identified heterocyclic variants of the (Z)-2-benzylidene-6-hydroxybenzofuran-3(2H)-one scaffold that possessed low nanomolar in vitro potency in cell proliferation assays using various cancer cell lines, in vivo potency in prostate cancer PC-3 xenograft and zebrafish models, selectivity for the colchicine-binding site on tubulin, and absence of appreciable toxicity. Among the leading, biologically active analogs were (Z)-2-((2-((1-ethyl-5-methoxy-1H-indol-3-yl)methylene)-3-oxo-2,3-dihydrobenzofuran-6-yl)oxy)acetonitrile (5a) and (Z)-6-((2,6-dichlorobenzyl)oxy)-2-(pyridin-4-ylmethylene)benzofuran-3(2H)-one (5b) that inhibited in vitro PC-3 prostate cancer cell proliferation with IC50 values below 100 nM. A xenograft study in nude mice using 10 mg/kg of 5a had no effect on mice weight, and aurone 5a did not inhibit, as desired, the human ether-à-go-go-related (hERG) potassium channel. Cell cycle arrest data, comparisons of the inhibition of cancer cell proliferation by aurones and known antineoplastic agents, and in vitro inhibition of tubulin polymerization indicated that aurone 5a disrupted tubulin dynamics. Based on molecular docking and confirmed by liquid chromatography-electrospray ionization-tandem mass spectrometry studies, aurone 5a targets the colchicine-binding site on tubulin. In addition to solid tumors, aurones 5a and 5b strongly inhibited in vitro a panel of human leukemia cancer cell lines and the in vivo myc-induced T cell acute lymphoblastic leukemia (T-ALL) in a zebrafish model

Discovery and Development of Small-Molecule Inhibitors of Glycogen Synthase

The overaccumulation of glycogen appears as a hallmark in various glycogen storage diseases (GSDs), including Pompe, Cori, Andersen, and Lafora disease. Accumulating evidence suggests that suppression of glycogen accumulation represents a potential therapeutic approach for treating these GSDs. Using a fluorescence polarization assay designed to screen for inhibitors of the key glycogen synthetic enzyme, glycogen synthase (GS), we identified a substituted imidazole, (rac)-2-methoxy-4-(1-(2-(1-methylpyrrolidin-2-yl)ethyl)-4-phenyl-1H-imidazol-5-yl)phenol (H23), as a first-in-class inhibitor for yeast GS 2 (yGsy2p). Data from X-ray crystallography at 2.85 Å, as well as kinetic data, revealed that H23 bound within the uridine diphosphate glucose binding pocket of yGsy2p. The high conservation of residues between human and yeast GS in direct contact with H23 informed the development of around 500 H23 analogs. These analogs produced a structure–activity relationship profile that led to the identification of a substituted pyrazole, 4-(4-(4-hydroxyphenyl)-3-(trifluoromethyl)-1H-pyrazol-5-yl)pyrogallol, with a 300-fold improved potency against human GS. These substituted pyrazoles possess a promising scaffold for drug development efforts targeting GS activity in GSDs associated with excess glycogen accumulation

Rock fishladder as element of ecological corridor restoration for strongly degradeted rivers

W ostatnich dziesięcioleciach w wyniku regulacji rzek i przegradzania dolin rzecznych nastąpiły niekorzystne zmiany w hydromorfologii koryt rzecznych [Bartnik, 2006]. Zwiększenie retencji wodnej i wykorzystanie hydroenergetyczne rzek, które pociąga za sobą budowę nowych obiektów hydrotechnicznych wymaga nowego spojrzenia na ciągłość korytarza rzecznego. Zgodnie z RDW „silnie zmieniona część wód oznacza część wód powierzchniowych, których charakter został znacznie zmieniony na skutek fizycznego oddziaływania człowieka […]” [Dyrektywa 2000/60/WE]. W silnie zmienionych częściach wód należy dążyć do osiągnięcia dobrego potencjału ekologicznego wód. Nastąpić to może poprzez budowę lub przebudowę budowli wodnych w sposób umożliwiający odpowiednie warunki migracji i życia dla ryb i innych organizmów wodnych. Celem pracy jest wyznaczenie dopuszczalnych wymiarów konstrukcji przepławki ryglowej spełniające kryteria biologiczne ryb w zlewni rzeki Skawy. W tym celu zostały przeprowadzone pomiary laboratoryjne na fizycznym modelu przepławki ryglowej. Na podstawie badań modelowych przepławki ryglowej określono warunki stabilności biologicznej: przepływu, prędkości wody, napełnienia i dyssypacji objętościowej.In the recent decades, due to improper management of river ecosystems adverse effects occurred in riverbeds hydromorphology. Increased water retention and use of hydroelectric rivers, which entails the construction of new hydro power plants requires a new look at the continuity of the river corridor. According to the RDW "heavily modified water body means a body of surface water, the nature of which has been significantly altered as a result of physical alterations by human [...]"[Dyrektywa 2000/60/WE]. The heavily modified water bodies should aim to achieve good ecological potential of waters. It is to be achieved through the construction or reconstruction of water structures to ensure efficient migration and living conditions for fish and other aquatic organisms. The aim of this study is to determine the construction limits of rock fishladders that meet the biological criteria of fish in the Skawa river. Laboratory measurements were carried out on the physical model of rock fishladder. The results of laboratory measurement were used to calculate hydraulic condition within fishladder to determine biological stability of fishes: discharge, velocity of water, water depth and energy dissipation

Integrated management systems. Advantages and disadvantages; difficulties and recommendations in the process of implementation

W dzisiejszych czasach organizacje wciąż poszukują metod doskonalenia efektywności działania, które mają zagwarantować im przewagę konkurencyjną, stały zyskowny rozwój oraz zdolność przetrwania w turbulentnym otoczeniu. Coraz bardziej popularnym środkiem realizacji tych postulatów jest wdrażanie certyfikowanych systemów zarządzania. W artykule zaprezentowano przesłanki wdrażania zintegrowanego systemu zarządzania (ZSZ), charakterystykę najczęściej integrowanych systemów zarządzania, wady i zalety integracji oraz trudności podczas wdrażania ZSZ i rekomendacje dotyczące skuteczności integracji ZSZ.Nowadays, organisations are constantly looking for methods to improve their efficiency and to guarantee them a competitive advantage, sustainable profitable growth and ability to survive in a turbulent environment. An increasing popularity of implementation of certified management systems has been noticed. The most often integrated management system are eg. ISO 9001, ISO 14001, ISO 18001. The paper presents the conditions for the implementation of an integrated management system (IMS), the characteristics of the most integrated management systems, the advantages and disadvantages of integration and the difficulties in the implementation of IMS and recommendations regarding the effectiveness of the integration of IMS