Linear fusigen as the major hydroxamate siderophore of the ectomycorrhizal Basidiomycota Laccaria laccata and Laccaria bicolor

A screening for siderophores produced by the ectomycorrhizal fungi Laccaria laccata and Laccaria bicolor in synthetic low iron medium revealed the release of several different hydroxamate siderophores of which four major siderophores could be identified by high resolution mass spectrometry. While ferricrocin, coprogen and triacetylfusarinine C were assigned as well as other known fungal siderophores, a major peak of the siderophore mixture revealed an average molecular mass of 797 for the iron-loaded compound. High resolution mass spectrometry indicated an absolute mass of m/z = 798.30973 ([M + H]⁺). With a relative error of Δ = 0.56 ppm this corresponds to linear fusigen (C₃₃H₅₂N₆O₁₃Fe; MW = 797.3). The production of large amounts of linear fusigen by these basidiomycetous mycorrhizal fungi may possibly explain the observed suppression of plant pathogenic Fusarium species. For comparative purposes Fusarium roseum was included in this study as a well known producer of cyclic and linear fusigen.     

Synthesis of novel acridine and bis acridine sulfonamides with effective inhibitory activity against the cytosolic carbonic anhydrase isoforms II and VII

4-Amino-N-(4-sulfamoylphenyl)benzamide was synthesized by reduction of 4-nitro-N-(4-sulfamoylphenyl)benzamide and used to synthesize novel acridine sulfonamide compounds, by a coupling reaction with cyclic-1,3-diketones and aromatic aldehydes. The new compounds were investigated as inhibitors of the metalloenzyme carbonic anhydrase (CA, EC 4.2.1.1), and more precisely the cytosolic isoforms hCA I, II and VII. hCA I was inhibited in the micromolar range by the new compounds (K_Is of 0.16–9.64 μM) whereas hCA II and VII showed higher affinity for these compounds, with K_Is in the range of 15–96 nM for hCA II, and of 4–498 nM for hCA VII. The structure–activity relationships for the inhibition of these isoforms with the acridine–sulfonamides reported here were also elucidated.     

Synthesis and carbonic anhydrase inhibitory properties of sulfamides structurally related to dopamine

A series of novel sulfamides incorporating the dopamine scaffold were synthesized. Reaction of amines and tert-butyl-alcohol/benzyl alcohol in the presence of chlorosulfonyl isocyanate (CSI) afforded sulfamoyl carbamates, which were converted to the title compounds by treatment with trifluoroacetic acid or by palladium-catalyzed hydrogenolysis. Inhibition of six α-carbonic anhydrases (CAs, EC 4.2.1.1), that is, CA I, CA II, CA VA, CA IX, CA XII and CA XIV, and two β-CAs from Candida glabrata (CgCA) and Mycobacterium tuberculosis (Rv3588) with these sulfamides was investigated. All CA isozymes were inhibited in the low micromolar to nanomolar range by the dopamine sulfamide analogues. K_is were in the range of 0.061–1.822 μM for CA I, 1.47–2.94 nM for CA II, 2.25–3.34 μM for CA VA, 0.041–0.37 μM for CA IX, 0.021–1.52 μM for CA XII, 0.007–0.219 μM for CA XIV, 0.35–5.31 μM for CgCA and 0.465–4.29 μM for Rv3588. The synthesized sulfamides may lead to inhibitors targeting medicinally relevant CA isoforms with potential applications as antiepileptic, antiobesity antitumor agents or anti-infective.     

Synthesis and pharmacological investigation of new N-hydroxyalkyl-2-aminophenothiazines exhibiting marked MDR inhibitory effect

Novel N-hydroxyalkyl-2-aminophenothiazines implying a tetrazole moiety at the alkyl chain have been synthesized by hydroboration–oxidation of dienes followed by Buchwald–Hartwig cross-coupling reaction. Also, some sulfoxide and sulfone derivatives have been prepared by selective oxidations. MDR inhibition studies on rat hepatocyte cell culture revealed that some derivatives exhibit marked biological efficacy exceeding that of the standard verapamil (e.g., 3h, 4h, 16). Selected derivatives were subjected to chemical resolution to provide both enantiomers which were shown of similar activity on P-gp interaction measurements. The new compounds exhibited no toxicity.     

Genetik des essenziellen Tremors

Essential tremor (ET) is—with a lifetime prevalence of approximately 1?%—one of the commonest movement disorders. ET patients predominantly suffer from a postural and kinetic tremor of the arms which might severely impair fine motor skills. The question whether additional symptoms such as mild cognitive deficits and depression, which occur in some patients, belong to the clinical picture of ET is a matter of debate. More than 50?% of all ET patients have a positive family history. In many families ET segregates in a manner compatible with autosomal dominant transmission. Recently mutations in the fused in sarcoma (FUS) gene have been identified as one potential cause of monogenic ET. In the majority of patients ET is genetically complex. Twin studies suggest a very high heritability. Two relatively small genome-wide association studies identified risk variants in the LINGO1 gene which plays a role in neuroregeneration and in the SLC1A2 gene which encodes the most important glutamate reuptake transporter of the brain.     

Turkey as a crossroad for Greater Flamingos Phoenicopterus roseus: evidence from population trends and ring-resightings (Aves: Phoenicopteridae)

The Greater Flamingo Phoenicopterus roseus is a waterbird commonly found in saline and brackish lagoons throughout the Mediterranean Region. We have gathered existing data on Greater Flamingos in Turkey and carried out field surveys to present the most up to date information on wintering (1999–2014) and breeding (1969– 2014). The wintering population of flamingos shows an increasing trend with 54,947±20,794 individuals mainly concentrated in the Gediz, Büyük Menderes and Çukurova deltas, respectively. Breeding attempts were recorded in at least seven wetlands in Turkey in the past, yet after 1999 most of the colonies were abandoned due to basin scale intensive water management practices in Central Anatolia. Currently, only Tuz Lake and Gediz Delta are used as regular breeding sites, while breeding has been recorded sporadically in Ac?göl and Ak?ehir Lakes. The breeding colony of Tuz Lake is of prime importance at the Mediterranean scale, with the number of young chicks in 2011, 2012 and 2013 accounting for the highest number of fledglings in the Mediterranean Region and West Africa (18,418, 20,274 and 20,292 respectively). Finally, building upon the previous findings about Turkey and the western Mediterranean metapopulation links, recent resightings of Turkish flamingos (despite the limited numbers) confirm post-fledging and natal dispersal reaching the western Mediterranean Basin and West Africa. Flamingos from Turkey were also found to disperse to Israel and to a region outside the known flyways of the western Mediterranean and West African flamingos (i.e. to Israel and UAE). Thus, Turkey, due to its geographic position, appears to be a crossroad between the western and eastern Mediterranean Region and southwest Asia.     

Role of curcumin in the conversion of asparagine into acrylamide during heating

This study aimed to investigate the ability of curcumin to convert asparagine into acrylamide during heating at different temperatures. Binary and ternary model systems of asparagine–curcumin and asparagine–curcumin–fructose were used to determine the role of curcumin on acrylamide formation in competitive and uncompetitive reaction conditions. The results indicated that curcumin could potentially contribute to acrylamide formation under long-term heating conditions as long as asparagine was present in the medium. The amount of acrylamide formed in the ternary system was slightly higher than in the binary system during heating (p < 0.05), because of the higher concentrations of carbonyl compounds initially available. The kinetic trends were similar in both model systems evidencing that fructose reacted with asparagine more rapidly than curcumin. The data reveal that acrylamide formation in the temperature range of 150–200°C obeys Arrhenius law with activation energy of 79.1 kJ/mole. Data of this work showed the possibility that antioxidants having a carbonyl compound can react directly with ASN leading to acrylamide. The addition of antioxidants to foods may increase the formation of acrylamide upon long-term heating if free sugar concentration is low and ASN concentration is relatively high.     

Collagen XVI in health and disease

Collagen XVI, by structural analogy a member of the FACIT- (fibril-associated collagens with interrupted triple helices) family of collagens, is described as a minor collagen component of connective tissues. Collagen XVI is expressed in various cells and tissues without known occurrence of splice variants or isoforms. For skin and cartilage tissues its suprastructure is known. Presumably, there it acts as an adaptor protein connecting and organizing large fibrillar networks and thus modulates integrity and stability of the extracellular matrix (ECM).Collagen XVI is produced by myofibroblasts in the normal intestine and its synthesis is increased in the inflamed bowel wall where myofibroblasts develop increased numbers of focal adhesion contacts on collagen XVI. Consequently, recruitment of α1 integrin into the focal adhesions at the tip of the cells is induced followed by increased cell spreading on collagen XVI. This presumably adds to the maintenance of myofibroblasts in the inflamed intestinal regions and thus promotes fibrotic responses of the tissue. Notably, α1/α2 integrins interact with collagen XVI through an α1/α2β1 integrin binding site located in the COL 1–3 domains.Collagen XVI may act as a substrate for adhesion and invasion of connective tissue tumor cells. In glioblastoma it induces tumor invasiveness by modification of the β1-integrin activation pattern. Thus, altering the cell–matrix interaction through collagen XVI might be a molecular mechanism to further augment the invasive phenotype of glioma cells. In this line, in oral squamous cell carcinoma collagen XVI expression is induced which results in an upregulation of Kindlin-1 followed by an increased interaction with beta1-integrin. Consequently, collagen XVI induces a proliferative tumor phenotype by promoting an early S-phase entry.In summary, collagen XVI plays a decisive role in the interaction of connective tissue cells with their ECM, which is impaired in pathological situations. Alteration of tissue location and expression level of collagen XVI appears to promote tumorigenesis and to perpetuate inflammatory reactions.     

Land use and host neighbor identity effects on arbuscular mycorrhizal fungal community composition in focal plant rhizosphere

Arbuscular mycorrhizal fungi (AMF) provide a number of ecosystem services as important members of the soil microbial community. Increasing evidence suggests AMF diversity is at least partially controlled by the identities of plants in the host plant neighborhood. However, much of this evidence comes from greenhouse studies or work in invaded systems dominated by single plant species, and has not been tested in species-rich grasslands. We worked in 67 grasslands spread across the three German Biodiversity Exploratories that are managed primarily as pastures and meadows, and collected data on AMF colonization, AMF richness, AMF community composition, plant diversity, and land use around focal Plantago lanceolata plants. We analyzed the data collected within each Exploratory (ALB Schwäbische Alb, HAI Hainich-Dün, SCH Schorfheide-Chorin) separately, and used variance partitioning to quantify the contribution of land use, host plant neighborhood, and spatial arrangement to the effect on AMF community composition. We performed canonical correspondence analysis to quantify the effect of each factor independently by removing the variation explained by the other factors. AMF colonization declined with increasing land use intensity (LUI) along with concurrent increases in non-AMF, suggesting that the ability of AMF to provide protection from pathogens declined under high LUI. In ALB and HAI mowing frequency and percent cover of additional P. lanceolata in the host plant neighborhood were important for AMF community composition. The similar proportional contribution of land use and host neighborhood to AMF community composition in a focal plant rhizosphere suggests that the diversity of this important group of soil microbes is similarly sensitive to changes at large and small scales.