A canine DNM1 mutation is highly associated with the syndrome of exercise-induced collapse

Labrador retrievers are the most common dog breed in the world, with over 200,000 new kennel club registrations per year. The syndrome of exercise-induced collapse (EIC) in this breed is manifested by muscle weakness, incoordination and life-threatening collapse after intense exercise. Using a genome-wide microsatellite marker scan for linkage in pedigrees, we mapped the EIC locus to canine chromosome 9. We then used SNP association and haplotype analysis to fine map the locus, and identified a mutation in the dynamin 1 gene (DNM1) that causes an R256L substitution in a highly conserved region of the protein. This first documented mammalian DNM1 mutation is present at a high frequency in the breed and is a compelling candidate causal mutation for EIC, as the dynamin 1 protein has an essential role in neurotransmission and synaptic vesicle endocytosis.     

Self-directed self-assembly of nanoparticle/copolymer mixtures

The organization of inorganic nanostructures within self-assembled organic or biological templates is receiving the attention of scientists interested in developing functional hybrid materials. Previous efforts have concentrated on using such scaffolds to spatially arrange nanoscopic elements as a strategy for tailoring the electrical, magnetic or photonic properties of the material. Recent theoretical arguments have suggested that synergistic interactions between self-organizing particles and a self-assembling matrix material can lead to hierarchically ordered structures. Here we show that mixtures of diblock copolymers and either cadmium selenide- or ferritin-based nanoparticles exhibit cooperative, coupled self-assembly on the nanoscale. In thin films, the copolymers assemble into cylindrical domains, which dictate the spatial distribution of the nanoparticles; segregation of the particles to the interfaces mediates interfacial interactions and orients the copolymer domains normal to the surface, even when one of the blocks is strongly attracted to the substrate. Organization of both the polymeric and particulate entities is thus achieved without the use of external fields, opening a simple and general route for fabrication of nanostructured materials with hierarchical order.     

Inhibition of acute inflammation by hyperlipemia

Zusammenfassung Experimentell wurde an R-Amsterdam-Ratten gezeigt, dass Triglyceride (Oleum helianthi und Lipofundin^®) die von Dextran und Carrageenin hervorgerufene akute Entzündung hemmen können, dass dies von der Triglycerid-Dosis abhängt und mit dem Serum-Triglycerid-Spiegel parallel läuft.     

On the urinary elimination of methoxypromazine in man

Zusammenfassung Die Ausscheidung eines neuen neuroleptisch wirksamen Phenothiazinderivates — Mopazin — im Harn wurde spektrophotometrisch und papierchromatographisch untersucht. Als wichtigstes Abbauprodukt wurde Methoxypromazin-sulfoxyd gefunden. Daneben waren unverändertes Methoxypromazin und 1–3 nicht identifizierte Abbauprodukte nachzuweisen. Bei den letzteren handelt es sich möglicherweise um Konjugate.     

Effect of choline salicylates and some other analogues of salicylic acid on the replication of EMC virus in vitro

Zusammenfassung Es wird eine 90–99,9%ige Hemmung in vitro der Replikation des EMC-Virus durch 0,5–2 m molare Lösungen folgender Salicylsäurederivate festgestellt: Cholinsalicylat, Cholinacetoxysalicylat und der Natriumsalze von 2-Merkaptobenzoesäure, Salicylsäure sowie Acetylsalicylsäure. Ferner wurde eine etwa 70%ige Hemmung des Natriumsalzes der Sulphosalicylsäure, des Cholin-p-chlorobenzoates, sowie des Cholin-o-chlorobenzoates beobachtet. Cholin-p-oxybenzoat und Cholin-p-acetoxybenzoat zeigten hingegen keine Hemmungsaktivität.

---

---

Acknowledgements: We are indebted to Drs. Z.Macho and T.Zawisza from the Department of Synthesis of Drugs, School of Medicine, Wroclaw, for donating of choline salicylates and other derivatives of benzoyl-choline⁶.     

Sexual dimorphism in contraction properties and fibre of the flexor carpi radialis muscle of the frog (Rana temporaria L.)

Zusammenfassung Es wird ein Sexualdimorphismus beim Daumenbeugemuskel (m. flexor carpi radialis) des Frosches (Rana temporaria L.) mit Bezug auf das Kontraktionsverhalten, wie auch in histochemischer Richtung, festgestellt. Kontraktions- und Relaxationszeit sind bei männlichen Muskeln veralaugsamt mit entsprechender ATPase-Aktivität. Saionbedingte, geschlechtstypische Testosteronkonzentrationen stehen damit im Zusammenhang.     

Non-steroidal anti-inflammatory drugs: Effects on the utilization of glucose and production of lactic acid in tissue culture

Zusammenfassung In der Kultur embryonalen Hühnchengewebes kommt es unter Einfluss nichtsteroider Antiphlogistica (Aspirin, Indomethacin, Mefenamicsäure) zu einer Steigerung des Glukoseverbrauchs bei gleichzeitiger Vermehrung der Milchsäureerzeugung. Der Milchsäureverbrauch verläuft in zwei Phasen, wobei der erste Gipfel bei geringsten Konzentrationen des Arzneimittels.auftritt.     

Serotonin inhibition of liver mitochondria swellingin vitro

Riassunto È stato studiato l'effetto della serotonina sul rigonfiamento dei mitocondriin vitro: si è trovato che la serotonina protegge i mitocondri dal rigonfiamento spontaneo che si ha quando vengono sospesi in soluzione isotonica di saccarosio.     

Open channel structure of MscL and the gating mechanism of mechanosensitive channels

Mechanosensitive channels act as membrane-embedded mechano-electrical switches, opening a large water-filled pore in response to lipid bilayer deformations. This process is critical to the response of living organisms to direct physical stimulation, such as in touch, hearing and osmoregulation. Here, we have determined the structural rearrangements that underlie these events in the large prokaryotic mechanosensitive channel (MscL) using electron paramagnetic resonance spectroscopy and site-directed spin labelling. MscL was trapped in both the open and in an intermediate closed state by modulating bilayer morphology. Transition to the intermediate state is characterized by small movements in the first transmembrane helix (TM1). Subsequent transitions to the open state are accompanied by massive rearrangements in both TM1 and TM2, as shown by large increases in probe dynamics, solvent accessibility and the elimination of all intersubunit spin-spin interactions. The open state is highly dynamic, supporting a water-filled pore of at least 25 A, lined mostly by TM1. These structures suggest a plausible molecular mechanism of gating in mechanosensitive channels.