Effects of colchicine and of emetine on capillary permeability]

Colchicine and emetine administered locally in the hind paw of the rats increased markedly the capillar permeability. The action may be strongly inhibited by methysergide (0.2 mug). Mepyramine (0.5 mug) is not so active and indomethacine (1 mg/kg per os), even less. As some prostaglandines release serotonine and histamine (8) it is possible that some liberation of these mediators may be attribuable to a previous release of prostaglandines, but the experiments suggest also the possibility of a direct and concomitant release of those two mediators by the alkaloids assayed.     

Galanin Reduces Carbachol Stimulation of Phosphoinositide Turnover in Rat Ventral Hippocampus by Lowering Ca2+ Influx Through Voltage-Sensitive Ca2+ Channels

The 29-amino-acid peptide galanin (GAL) caused concentration-dependent inhibition of the accumulation of 3H-inositol phosphates (3H-InsPs) induced by the muscarinic agonist carbachol (CARB; 10(-3)-10(-5) M) in the presence of 5 mM lithium, specifically in tissue miniprisms from rat ventral hippocampus. The inhibitory effect of GAL involved the mono-, bis-, tris-, and tetrakisphosphates formed during activation for 2 min of phospholipase C by CARB (1 mM) in the absence of lithium. GAL (1 microM) did not affect alpha-adrenergic or serotonergic type 2 receptor-mediated phosphoinositide (PI) breakdown in the same tissue. GAL by itself neither acted on basal levels of 3H-InsPs nor affected muscarinic receptors in binding studies. Blockade of the T-, N-, and L-types of voltage-sensitive calcium channel (VSCC) with 200 microM Cd2+ reduced muscarinic receptor-mediated PI breakdown by 50% and abolished the inhibitory effect of GAL (1 microM). Reduction of the extracellular Ca2+ concentration from 1.3 mM to 0.49 microM abolished the GAL inhibition of CARB-stimulated PI hydrolysis. Ca2+ influx promoted by 18 mM K+ depolarization or by 1 microM Bay K 8644, a selective agonist of the L-type VSCC, prevented the inhibitory effect of GAL. Blockade of the L-type VSCC with nifedipine (1 microM) potentiated the inhibitory effects of GAL without affecting muscarinic stimulation of PI breakdown.(ABSTRACT TRUNCATED AT 250 WORDS)     

Tracking and chasing in houseflies (Musca)

The flight trajectories of free flying female and male houseflies have been analyzed in 3 dimensions. Both female and male flies track other flies. The turning velocity α (around the vertical axis) is linearly dependent upon the horizontal angle ψ_F (that is the angle between the trajectory of the tracking fly and the target) for small values of ψ_F in females and for the whole range of ψ_F in males. The 3-dimensional velocity υ _xyz of the chasing fly is linearly dependent upon the distance between leading and chasing fly in males but not in females. Male chasing thus appears to be more efficient than female tracking. It is shown that earlier assumptions on visual control of flight in female flies derived from experiments on fixed flying flies are justified.     

Mutants of Bacillus subtilis affected in spore outgrowth.

Six mutants of Bacillus subtilis 168 that are temperature-sensitive in spore outgrowth were isolated. The outgrowth process proceeds normally at 35 degrees C, but at the non-permissive temperature (47 degrees C) it is arrested at a specific stage characteristic for each mutant strain. The mutants are not altered in vegetative growth whether at 35 degrees C or at 47 degrees C. They were characterized for their ability to synthesize RNA, proteins and DNA during outgrowth. A mutant defective in spore germination was also isolated; less than 5% of its spores can germinate at any of the temperatures tested. The mutations were mapped by means of transduction and transformation. The isolation of a number of outgrowth mutants which map at different loci and which affect outgrowth at different times is discussed in relation to the regulation of this process.     

How plate positioning impacts the biomechanics of the open wedge tibial osteotomy; a finite element analysis

A numerical model of the medial open wedge tibial osteotomy based on the finite element method was developed. Two plate positions were tested numerically. In a configuration, (a), the plate was fixed in a medial position and (b) in an anteromedial position. The simulation took into account soft tissues preload, muscular tonus and maximal gait load.The maximal stresses observed in the four structural elements (bone, plate, wedge, screws) of an osteotomy with plate in medial position were substantially higher (1.13-2.8 times more) than those observed in osteotomy with an anteromedial plate configuration. An important increase (1.71 times more) of the relative micromotions between the wedge and the bone was also observed. In order to avoid formation of fibrous tissue at the bone wedge interface, the osteotomy should be loaded under 18.8% (approximately 50 kg) of the normal gait load until the osteotomy interfaces union is achieved.     

Neural Tuning Size in a Model of Primate Visual Processing Accounts for Three Key Markers of Holistic Face Processing

Faces are an important and unique class of visual stimuli, and have been of interest to neuroscientists for many years. Faces are known to elicit certain characteristic behavioral markers, collectively labeled “holistic processing”, while non-face objects are not processed holistically. However, little is known about the underlying neural mechanisms. The main aim of this computational simulation work is to investigate the neural mechanisms that make face processing holistic. Using a model of primate visual processing, we show that a single key factor, “neural tuning size”, is able to account for three important markers of holistic face processing: the Composite Face Effect (CFE), Face Inversion Effect (FIE) and Whole-Part Effect (WPE). Our proof-of-principle specifies the precise neurophysiological property that corresponds to the poorly-understood notion of holism, and shows that this one neural property controls three classic behavioral markers of holism. Our work is consistent with neurophysiological evidence, and makes further testable predictions. Overall, we provide a parsimonious account of holistic face processing, connecting computation, behavior and neurophysiology.     

Dopamine Depletion Preferentially Impairs D1 over D2-Receptor Regulation of Striatal In Vivo Acetylcholine Release

The roles of D2 and D1 dopaminergic receptors on the regulation of striatal acetylcholine (ACh) release in vivo were examined for a period of 120 min after acute (2 h) or prolonged (16 h) depletion of brain dopamine (DA) by alpha-methyl-p-tyrosine. The reduction of DA transmission did not affect basal ACh output after 2 h but markedly lowered ACh release by 16 h (50%). Acute alpha-methyl-p-tyrosine pretreatment prevented the reduction of ACh release by the D1 antagonist SCH 23390 and its increase by the D2 antagonist, remoxipride, consistent with a drastic reduction of DA transmission at both DA receptors. However, 16 h after alpha-methyl-p-tyrosine, the effect of remoxipride on ACh release was restored, but SCH 23390 still had no effect, suggesting that the D2 inhibitory tone on ACh release had recovered, whereas the reduction of the D1 facilitatory influence persisted. The D1 facilitatory control of ACh neurotransmission thus appears to be more sensitive than the D2 inhibitory control to a reduction in DA transmission. The new model of DA-ACh interaction resulting from these data casts fresh light on the relationship between changes in DA transmission and extrapyramidal motor function.     

Nickel binding properties of Helicobacter pylori UreF,an accessory protein in the nickel-based activation of urease

Helicobacter pylori UreF (HpUreF) is involved in the insertion of Ni²⁺ in the urease active site. The recombinant protein in solution is a dimer characterized by an extensive α-helical structure and a well-folded tertiary structure. HpUreF binds two Ni²⁺ ions per dimer, with a micromolar dissociation constant, as shown by calorimetry. X-ray absorption spectroscopy indicated that the Ni²⁺ ions reside in a five-coordinate pyramidal geometry comprising exclusively N/O-donor ligands derived from the protein, including one or two histidine imidazole and carboxylate ligands. Binding of Ni²⁺ does not affect the solution properties of the protein. Mutation to alanine of His229 and/or Cys231, a pair of residues located on the protein surface that interact with H. pylori UreD, altered the affinity of the protein for Ni²⁺. This result, complemented by the findings from X-ray absorption spectroscopy, indicates that the Ni²⁺ binding site involves His229, and that Cys231 has an indirect structural role in metal binding. An in vivo assay of urease activation demonstrated that H229A HpUreF, C231A HpUreF, and H229/C231 HpUreF are significantly less competent in this process, suggesting a role for a Ni²⁺ complex with UreF in urease maturation. This hypothesis was supported by calculations revealing the presence of a tunnel that joins the Cys-Pro-His metal binding site on UreG and an opening on the UreD surface, passing through UreF close to His229 and Cys231, in the structure of the H. pylori UreDFG complex. This tunnel could be used to transfer nickel into the urease active site during apoenzyme-to-holoenzyme activation.