New tetromycin derivatives with anti-trypanosomal and protease inhibitory activities

Four new tetromycin derivatives, tetromycins 1-4 and a previously known one, tetromycin B (5) were isolated from Streptomyces axinellae Pol001(T) cultivated from the Mediterranean sponge Axinella polypoides. Structures were assigned using extensive 1D and 2D NMR spectroscopy as well as HRESIMS analysis. The compounds were tested for antiparasitic activities against Leishmania major and Trypanosoma brucei, and for protease inhibition against several cysteine proteases such as falcipain, rhodesain, cathepsin L, cathepsin B, and viral proteases SARS-CoV M(pro), and PL(pro). The compounds showed antiparasitic activities against T. brucei and time-dependent inhibition of cathepsin L-like proteases with K(i) values in the low micromolar range.     

cBSA-147 for the preparation of bacterial biofilms in a microchannel reactor

Whole cells are attractive biocatalysts, particularly if the reaction requires cofactors or involves multiple transformations. Immobilization of the catalyst is often a prerequisite for continuous processes. The highly cationic chemically modified plasma protein bovine serum albumin (cBSA-147) has been applied for the electrostatically mediated immobilization of the planktonic bacterium E. coli BL21 star (DE3), and the resulting biofilms were superior to those formed on poly-L-lysine coated surfaces. The biocatalyst was immobilized in a capillary column (inside diameter of 530?μm and L=30?m) and evaluated in the enantioselective reduction of ethyl acetoacetate to R-(-)ethyl hydroxybutyrate. In continuous operation in the microreactor format, the productivity of the cells was about 30% higher than that determined in a bench-scale fermentation system. This increase is attributed to the improved mass transfer over short geometrical dimensions. The similarity in the results indicates that studies on a biofilm-coated microreactor can be used for the accelerated collection of data for process optimization.     

Porcine circovirus type 2 (PCV2)-infection and re-inoculation with homologous or heterologous strains: virological, serological, pathological and clinical effects in growing pigs

Long-term PCV2 infection and/or concurrent infection with genotypes PCV2a and PCV2b may play a role in the development of clinical porcine circovirus-associated disease (PCVAD). To evaluate this premise, 24 11-week-old specific pathogen-free (SPF) pigs were randomly assigned to 1 of 4 treatments: negative controls, a single inoculation with PCV2a, single inoculation followed by re-inoculation with a homologous PCV2a strain, or repeated inoculations with heterologous strains (PCV2a, PCV2b). Pigs were evaluated for clinical signs daily through 140 days post inoculation (dpi). Serum samples were collected every other day from dpi 0 through 14 and weekly thereafter. PCV2-inoculated pigs were viremic by dpi 2 and 13 of 18 pigs remained viremic at 140 dpi. No statistical differences in the onset, level, or duration of PCV2 viremia were detected among treatment groups. Anti-PCV2 antibodies were detected between 14 and 28 dpi and were present through 140 dpi without statistical differences in antibody response among treatment groups. In the current study, pigs had extended viremia combined with detectable tissue PCV2 antigen levels despite the presence of high levels of anti-PCV2 antibody; however, no clinical disease was observed.     

Stammapplikationen im Obstbau mit nanostrukturierten Silikaten gegen die Blutlaus Eriosoma lanigerum (Hausm.) und den Gemeinen Ohrwurm Forficula auricularia L.

The present work deals with a new strategy to control Eriosoma lanigerum (Hausm.) in apple and Forficula auricularia?(L.) in apricots. With common insecticides, both pests are difficult to control. Although F.?auricularia is regarded as a beneficial insect, in ecological agriculture it has the potential to cause severe economical damage in apricots. In apple and apricot orchards we tested treatments on the bark with diatomaceous earth (DE) products to prevent insects from reaching the tree crown. DE has been applied as liquid (“Fossil Shield^®” translucend) by a backpack sprayer or electrostatically as powder (“Fossil Shield^®” 90.0?s). In some trials we covered the treated area with a plastic funnel (fruitcap) in order to protect the silica-product from wind and rain. Experiments were evaluated weekly and number of insects in the tree crown was counted. During the first two months after treatment E.?lanigerum population in the crown was reduced by 98.2%. However, over the whole period of six month the barriers turned out to be ineffective (p?=?0.617). Winged adults have been capable to pass the barriere. In contrast to this fruitcap barriers were able to keep F. auricularia away from the crown (p?=?0.000). They have been as effective as standard treatment using glue. In such treatments apricot yield increased 6-fold for the cultivar “Goldrich” and 5.5-fold for the cultivar “Hargrand”.     

Nano-sized albumin-copolymer micelles for efficient doxorubicin delivery

We present the discovery of a nano-sized protein-derived micellar drug delivery system based on the polycationic albumin precursor protein cBSA-147. The anticancer drug doxorubicin (DOX) was efficiently encapsulated into nanosized micelles based on hydrophobic interactions with the polypeptide scaffold. These micelles revealed attractive stabilities in various physiological buffers and a wide pH range as well as very efficient uptake into A549 cells after 1 h incubation time only. In vitro cytotoxicity was five-times increased compared to free DOX also indicating efficient intracellular drug release. In addition, multiple functional groups are available for further chemical modifications. Based on the hydrophobic loading mechanism, various classical anti-cancer drugs, in principle, could be delivered even synergistically in a single micelle. Considering these aspects, this denatured albumin-based drug delivery system represents a highly attractive platform for nanomedicine approaches towards cancer therapy.     

Antioxidant and Anti-Protease Activities of Diazepinomicin from the Sponge-Associated Micromonospora Strain RV115

Diazepinomicin is a dibenzodiazepine alkaloid with an unusual structure among the known microbial metabolites discovered so far. Diazepinomicin was isolated from the marine sponge-associated strain Micromonospora sp. RV115 and was identified by spectroscopic analysis and by comparison to literature data. In addition to its interesting preclinical broad-spectrum antitumor potential, we report here new antioxidant and anti-protease activities for this compound. Using the ferric reducing antioxidant power (FRAP) assay, a strong antioxidant potential of diazepinomicin was demonstrated. Moreover, diazepinomicin showed a significant antioxidant and protective capacity from genomic damage induced by the reactive oxygen species hydrogen peroxide in human kidney (HK-2) and human promyelocytic (HL-60) cell lines. Additionally, diazepinomicin inhibited the proteases rhodesain and cathepsin L at an IC₅₀ of 70–90 µM. It also showed antiparasitic activity against trypomastigote forms of Trypanosoma brucei with an IC₅₀ of 13.5 µM. These results showed unprecedented antioxidant and anti-protease activities of diazepinomicin, thus further highlighting its potential as a future drug candidate.     

Influence of the excystment time on the breeding success of juvenile freshwater pearl mussels (Margaritifera margaritifera)

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Degradation of citrate promotes copper co-precipitation within aluminium-(hydr)oxides in calcareous soils

In this study, we provide experimental evidences that in calcareous soils microbial degradation/decomposition of citrate can promote Al-(hydr)oxide precipitation concurrently decreasing copper (Cu) solubility by a coprecipitation process. Citrate is an organic acid anion commonly released by roots to increase nutrient availability or to limit Al toxicity. However, under specific environmental conditions (i.e. high microbial activity of Al-citrate-degrading bacteria, alkaline pH), this organic acid may become ineffective in mobilizing Cu for the plant acquisition process. To demonstrate this, a calcareous soil and an artificial soil system have been treated with citrate solutions; then, changes in Al and Cu solubility and the formation of Cu-containing Al-(hydr)oxides were monitored. Both in experiments with the artificial soil and in those where the soil was inoculated with microbial strains, the formation of Cu-Al coprecipitates not only occurred but was also concurrent with the decrease of Cu and Al solubility. The role of bacteria in metal-citrate complex degradation has been assessed, and the 16S rDNA of bacteria related with these processes has been sequenced for genus identification. Bacteria belonging to Pseudomonas, Sphingomonas, Bradyrhizobium and Sphingopixis have been identified as possible candidates to degrade Al- and Cu-citrate complexes thus triggering the metal precipitation phenomena.