Antibiotics from basidiomycetes. XXXII. Strobilurin E: a new cytostatic and antifungal (E)-beta-methoxyacrylate antibiotic from Crepidotus fulvotomentosus Peck

Strobilurin E is a novel antibiotic of the (E)-beta-methoxyacrylate (MOA) class produced by mycelial cultures of the agaric Crepidotus fulvotomentosus. In addition to an inhibition of fungal respiration, a feature of all MOA-antibiotics, the compound exhibits very high cytostatic activities which are accompanied by reversible morphological alterations of the cells.     

Asperfuran, a novel antifungal metabolite from Aspergillus oryzae

Asperfuran is a novel antifungal dihydrobenzofuran derivative produced by a strain of Aspergillus oryzae. Asperfuran weakly inhibited chitin synthase from Coprinus cinereus. This inhibition could be abolished by the addition of egg lecithin. In the agar diffusion assay asperfuran induced morphological changes in Mucor miehei at very low concentrations (20 ng/disc) while growth was only partly inhibited. In HeLa S3 and L1210 cells it showed weak cytotoxicity, the IC50 was 25 micrograms/ml.     

Clinical characteristics of driving phobia

Fifty-six subjects who were afraid of driving were recruited by advertisement and compared to 31 controls without this fear. Subjects were interviewed and given several questionnaires to gather information for making DSM-III-R diagnoses and to determine their agoraphobia avoidance behavior, driving history, and the history of their phobia. Our sample had a mean age of 48, was 82% female, and typically feared and avoided driving on freeways, bridges, and through tunnels, but were not so fearful about driving on quiet residential streets. Diagnostically, 81% of the phobics reported having had panic attacks, but only 14% (8/56) met criteria for Panic Disorder. Although on average phobics had had no more automobile accidents than controls, 15% (8/55) reported an accident as the primary reason for their phobia. The 53% (29/55) who reported panic attacks as the primary reason for their phobia were more concerned about anxiety symptoms while driving than phobics who gave other, nonaccident-related reasons for their phobia. We conclude that many driving phobics do not fit neatly into current DSM-III-R anxiety disorder categories, because they combine characteristics of Simple Phobia and Panic Disorder with Agoraphobia without meeting the criteria for either disorder.     

45Interaction between Hsp70 and bis(monoacylglycero)phosphate stabilizes lysosomes and promotes cell survival

Lysosomal membrane permeabilization is an evolutionarily conserved hallmark of stress-induced cell death. Here we show that the major stress-inducible heat shock protein 70 (Hsp70) enhances cell survival by stabilizing lysosomes through a pH-dependent high affinity binding to an endo-lysosomal anionic phospholipid bis(monoacylglycero)phosphate (BMP; also referred to as lysobisphosphatidic acid). The positively charged ATPase domain of Hsp70 is responsible for the binding but the substrate-binding domain is also required for effective stabilization of lysosomes. Importantly, the cytoprotective effect can be obtained by endocytic delivery of recombinant Hsp70 and specifically reverted by extra cellular administration of BMP antibodies or Hsp70 inhibitors. Thus, this protein-lipid interaction opens exciting possibilities for the development of cytoprotective and cytotoxic lysosome-specific therapies for the treatment of degenerative diseases and cancer, respectively.     

Val103Ile polymorphism of the melanocortin-4 receptor gene (<Emphasis Type="Italic">MC4R</Emphasis>) in cancer cachexia

Background  

At present pathogenic mechanisms of cancer cachexia are poorly understood. Previous evidence in animal models implicates the melanocortin-4 receptor gene (MC4R) in the development of cancer cachexia. In humans, MC4R mutations that lead to an impaired receptor function are associated with obesity; in contrast, the most frequent polymorphism (Val103Ile, rs2229616; heterozygote frequency approximately 2%) was shown to be negatively associated with obesity. We tested if cancer patients that are homo-/heterozygous for the Val103Ile polymorphism are more likely to develop cachexia and/or a loss of appetite than non-carriers of the 103Ile-allele.