Immunomodulatory Properties of Filamentous Fungi Cultivated through Solid-State Fermentation on Rapeseed Meal

Water extracts from solid-state fermentation (SSF) on rapeseed meal using filamentous fungi exhibit interesting immunomodulatory activities in vitro. Immunomodulation was determined by the capacity of the compounds to activate blood neutrophils and to influence cytokine production in human peripheral blood mononuclear cells (PBMC) and mouse bone marrow-derived macrophages (BMDM). Among the strains tested, Aspergillus sojae mycelium and SSF extracts were the most promising in terms of enhancing the immune response. The filamentous fungus was also successfully cultivated in a pre-pilot bioreactor with forced aeration. The results indicated that the extracts not only activated blood neutrophils but also significantly modulated IL-1β cytokine levels with lipopolysaccharide (LPS)-stimulated PBMC and BMDM without any cytotoxicity in immune cells. IL-1β was down-regulated in a dose-dependent manner in the presence of A. sojae crude mycelium and SSF extract with PBMC, which indicated that there was an anti-inflammatory activity, whereas IL-1β secretion was up-regulated in the presence of stimulated BMDM with the highest concentration that was tested (100 μg/mL). The non-fermented rapeseed had no effect at the same concentration. SSF culture, as a natural product, may be a good source for the development of functional feed with an immunostimulating effect or could potentially be used in medicinal applications.     

Recurrence properties of sequences of integers

In order to study the recurrence of sequences of integers, we investigate their L2-exactness and Θ-Hartman property (Θ being a set of rational numbers). Two classes of sequences of integers are well studied, which are return times relative to a weakly mixing system and Bernoulli random sequences.     

Sanglifehrin-cyclophilin interaction: degradation work,synthetic macrocyclic analogues,X-ray crystal structure,and binding data

Sanglifehrin A (SFA) is a novel immunosuppressive natural product isolated from Streptomyces sp. A92-308110. SFA has a very strong affinity for cyclophilin A (IC(50) = 6.9 +/- 0.9 nM) but is structurally different from cyclosporin A (CsA) and exerts its immunosuppressive activity via a novel mechanism. SFA has a complex molecular structure consisting of a 22-membered macrocycle, bearing in position 23 a nine-carbon tether terminated by a highly substituted spirobicyclic moiety. Selective oxidative cleavage of the C(26)=C(27) exocyclic double bond affords the spirolactam containing fragment 1 and macrolide 2. The affinity of 2 for cyclophilin (IC(50) = 29 +/- 2.1 nM) is essentially identical to SFA, which indicates that the interaction between SFA and cyclophilin A is mediated exclusively by the macrocyclic portion of the molecule. This observation was confirmed by the X-ray crystal structure resolved at 2.1 A of cyclophilin A complexed to macrolide 16, a close analogue of 2. The X-ray crystal structure showed that macrolide 16 binds to the same deep hydrophobic pocket of cyclophilin A as CsA. Additional valuable details of the structure-activity relationship were obtained by two different chemical approaches: (1) degradation work on macrolide 2 or (2) synthesis of a library of macrolide analogues using the ring-closing metathesis reaction as the key step. Altogether, it appears that the complex macrocyclic fragment of SFA is a highly optimized combination of multiple functionalities including an (E,E)-diene, a short polypropionate fragment, and an unusual tripeptide unit, which together provide an extremely strong affinity for cyclophilin A.     

Capillary supercritical fluid chromatography with ultraviolet multichannel detection of some pesticides and herbicides

The useful combination of capillary supercritical fluid chromatography with ultraviolet multichannel detection is demonstrated by the analysis of selected pesticides and herbicides. In this application the advantages of compound identification by ultraviolet spectrometry are appended to the separating capability of capillary supercritical fluid chromatography. A pseudo oncolumn detection approach is used. Compromises from the theoretically ideal conditions for both capillary SFC and the multichannel UV detector are made to achieve a practical interfacing of the chromatographic and spectrophotometric techniques. Detection limits are at the low nanogram levels.