Showing papers by "University of Tübingen published in 1991"

Pharmacology of Curcuma longa

Abstract: The data reviewed indicate that extracts of Curcuma longa exhibit anti-inflammatory activity after parenteral application in standard animal models used for testing anti-inflammatory activity It turned out that curcumin and the volatile oil are at least in part responsible for this action It appears that when given orally, curcumin is far less active than after ip administration This may be due to poor absorption, as discussed Data on histamine-induced ulcers are controversial, and studies on the secretory activity (HCl, pepsinogen) are still lacking In vitro, curcumin exhibited antispasmodic activity Since there was a protective effect of extracts of Curcuma longa on the liver and a stimulation of bile secretion in animals, Curcuma longa has been advocated for use in liver disorders Evidence for an effect on liver disease in humans is not yet available From the facts that after oral application only traces of curcumin were found in the blood and that, on the other hand, most of the curcumin is excreted via the faeces it may be concluded that curcumin is absorbed poorly by the gastrointestinal tract and/or underlies presystemic transformation Systemic effects therefore seem to be questionable after oral application except that they occur at very low concentrations of curcumin This does not exclude a local action in the gastrointestinal tract

Cerebellar dysmetria at the elbow, wrist, and fingers.

Abstract: 1. The objective was to investigate in cerebellar patients with dysmetria the kinematic and electromyographic (EMG) characteristics of large and small movements at the elbow, wrist, and finger and thereby to determine the nature of cerebellar dysmetria at distal as well as proximal joints. Flexions were made as fast as possible by moving relatively heavy manipulanda for each joint to the same end position through 5, 30, and 60 degrees. 2. In normal subjects flexions at all joints were accompanied by similar triphasic EMG activity. Movements of increasing amplitude were made with increasing movement durations and increasing durations and magnitudes of initial agonist EMG activity. Antagonist activity often appeared to have two components: one coactive with the initial agonist burst but starting later, the other reaching its peak at about peak velocity. 3. Cerebellar patients with dysmetria showed hypermetria followed by tremor at all three joints when movements were made with the manipulanda. Hypermetria was most marked for aimed movements of small amplitude (5 degrees) at all joints. 4. A characteristic of cerebellar disordered movements, which could be present at all amplitudes and all joints, was an asymmetry with decreased peak accelerations and increased peak decelerations compared to normal movements. Both the asymmetry and the hypermetria for small amplitude movements could be used clinically as sensitive indicators of cerebellar dysfunction. 5. The EMG abnormalities accompanying hypermetria and asymmetry were a more gradual buildup and a prolongation of agonist activity and delayed onset of antagonist activity.(ABSTRACT TRUNCATED AT 250 WORDS)

Exact prediction of a natural T cell epitope.

Abstract: T lymphocytes recognize their antigen as peptides associated with major histocompatibility complex (MHC) molecules Peptides naturally presented by MHC class I molecules are uniform in length and have a specific motif, both defined by the respective MHC allele (Falk, K et al Nature 1991 351:290) These allele-specific motifs should allow exact prediction of natural T cell epitopes H-2Kb-restricted epitopes, for example, have a length of eight amino acid residues and conserved anchor residues at positions 5 and 8 According to this information, we predicted the natural Kb-restricted epitope of ovalbumin, thought to be contained in the 19-mer IINFEKLTEWTSSNVMEER, to be SIINFEKL Here we show that this prediction is correct Thus, exact prediction of natural T cell epitopes is possible

Lantibiotics—Ribosomally Synthesized Biologically Active Polypeptides containing Sulfide Bridges and α,β‐Didehydroamino Acids

Abstract: Lantibiotics are polycyclic peptide antibiotics containing intrachain sulfide bridges, formed from the thioether groups of the amino acids lanthionine and β-methyllanthionine. They also contain α,β-unsaturated amino acids such as didehydroalanine and didehydroaminobutyric acid. A knowledge of the lantibiotic biosynthetic steps and the enzymes involved makes possible a gene technological construction of analogous highly modified polypeptides. To the family of lantibiotics belong nisin, an important food preservative, epidermin, a highly specific therapeutic agent against acne, a series of enzyme inhibitors, as well as immunologically interesting active peptides. Lantibiotics are produced by ribosomal synthesis, starting from inactive precursor proteins (prelantibiotics). The latter are post-translationally converted into the active peptide antibiotics through enzymic modifications. The modifying enzymes effect dehydrations at the serine and threonine residues and stereospecific additions of the cysteine thiol groups to the resulting α,β-unsaturated double bonds, which lead to the formation of several sulfide bridges. Upon subsequent proteolytic cleavage of the leader peptide, the biologically active lantibiotic is formed. Conformational analyses of the lantibiotics, as well as of their prepeptides, enables one to obtain information about the mechanism and steps of the biosynthesis. Antibodies against synthetic prepeptide sequences, and modern instrumental methods for the analysis of peptides, allow structural elucidation of the biosynthetic intermediates.

Auxin induces exocytosis and the rapid synthesis of a high-turnover pool of plasma-membrane H(+)-ATPase.

Abstract: Auxin causes elongation growth of plant cells by increasing the plastic extensibility of the cell wall. Putative cellular events involved in this hormone action were studied using maize (Zea mays L.) coleoptiles with the following results: (i) Auxin enhances membrane flow from the endoplasmic reticulum to the plasma membrane (PM). This effect was demonstrated by pulse-labeling of the endoplasmic reticulum with myo-[3H]inositol in coleoptile segments and by measuring the distribution of the label within isolated and separated microsomal membrane fractions, (ii) Auxin rapidly increases the amount of antibody-detectable H+-ATPase in the PM. This augmentation is already significant 10 min after the addition of indole-3-acetic acid (IAA) and reaches a new higher steady-state level after about 30 min. (iii) Cycloheximide, a potent inhibitor of both protein synthesis and extension growth, quickly diminishes the auxin-enhanced level of the PM H+-ATPase, indicating an apparent half-life of the enzyme of around 12 min. (iv) Cordycepin, which blocks the synthesis of mRNAs, reduces the auxin-elevated level of the H+-ATPase similar to cycloheximide. (v) Changes in the growth rate of coleoptile segments in response to IAA, cycloheximide, and cordycepin exactly reflect the changes of the H+-ATPase level in the PM. (vi) The elongation growth induced by fusicoccin, or ester compounds, or by an elevated CO2 concentration in the incubation medium, is not related to an increased number of H+-ATPase molecules within the PM. (vii) The necessity of H+ for cell-wall-loosening processes is again demonstrated by growth experiments with abraded coleoptile segments. The adjustment of the cell wall to a pH of ≥6.5 completely abolishes the auxin-induced elongation growth; no inhibition occurs with non-abraded segments. Buffer solutions of pH ≤6.0 induce “acid growth” of abraded segments for several hours. It is suggested that auxin activates a cluster of genes responsible (i) for the induction and acceleration of exocytotic processes (e.g. by the synthesis of either proteins, necessary for the fusion of membranes, or of other effectors); (ii) for the synthesis of PM H+-ATPases, increasing the capacity for H+-extrusion into the apoplast as a precondition for wall enlargement (“acid growth”); (iii) for a supposed synthesis and exocytosis of certain proteins, enzymes and wall precursors necessary for wall metabolism and the “repair” of the proton-loosened and turgor-stretched cell wall. Both, fusicoccin and auxin affect cell-wall plasticity according to the “acid-growth” theory. However, the mechanisms leading to this event are completely different; the auxinenhanced H+-extrusion is a gene-controlled process.

Towards the Chemical Synthesis of Proteins

Abstract: The chemical total synthesis of proteins using solid supports has made great progress. It is therefore becoming a reality what E. Fischer already predicted in 1902: “I foresee the time when physiological chemistry… is able to prepare synthetic enzymes.” The synthesis of peptides of up to 20 amino acids by the well-established solid-phase procedure on polymeric supports (SPPS) has made great progress through the development of newer supports. At the same time, methods have emerged which facilitate the separation and characterization of peptides, thus allowing optimization of the synthesis of pure materials. The new supports which enable one to synthesize peptides by a rapid continuous flow procedure are characterized by hydrophilicity, beads of approximately equal size, similar swelling properties in the solvents used for peptide synthesis, and stability at high pressure. With graft copolymers of weakly cross-linked polystyrene and linear polyethylene glycol (PEG), the synthetic cycle for coupling of one amino acid can routinely be reduced to 10–20 min with a concomitant higher yield. With beads of monodispersed graft copolymer of 10 μm diameter, a synthetic cycle can, in principle, be shortened to 1–5 min. By utilizing this high-speed solid-phase procedure, larger peptides up to the size of proteins could also be prepared in a few hours. With newer mass spectroscopic methods such as ion-spray mass spectrometry, peptides of up to a molecular mass of 100 kDa can be characterized, and with the advent of capillary electrophoresis, another very efficient separation tool, besides HPLC, is at our disposal.

Yeast cell cycle protein CDC48p shows full-length homology to the mammalian protein VCP and is a member of a protein family involved in secretion, peroxisome formation, and gene expression.

Abstract: Yeast mutants of cell cycle gene cdc48-1 arrest as large budded cells with microtubules spreading aberrantly throughout the cytoplasm from a single spindle plaque. The gene was cloned and disruption proved it to be essential. The CDC48 sequence encodes a protein of 92 kD that has an internal duplication of 200 amino acids and includes a nucleotide binding consensus sequence. Vertebrate VCP has a 70% identity over the entire length of the protein. Yeast Sec18p and mammalian N-ethylmaleimide-sensitive fusion protein, which are involved in intracellular transport, yeast Pas1p, which is essential for peroxisome assembly, and mammalian TBP-1, which influences HIV gene expression, are 40% identical in the duplicated region. Antibodies against CDC48 recognize a yeast protein of apparently 115 kD and a mammalian protein of 100 kD. Both proteins are bound loosely to components of the microsomal fraction as described for Sec18p and N-ethylmaleimide-sensitive fusion protein. This similarity suggests that CDC48p participates in a cell cycle function related to that of N-ethylmaleimide-sensitive fusion protein/Sec18p in Golgi transport.

General-relativistic celestial mechanics. I. Method and definition of reference systems.

Abstract: We present a new formalism for treating the general-relativistic celestial mechanics of systems of $N$ arbitrarily composed and shaped, weakly self-gravitating, rotating, deformable bodies. This formalism is aimed at yielding a complete description, at the first post-Newtonian approximation level, of (i) the global dynamics of such $N$-body systems ("external problem"), (ii) the local gravitational structure of each body ("internal problem"), and, (iii) the way the external and the internal problems fit together ("theory of reference systems"). This formalism uses in a complementary manner $N+1$ coordinate charts (or "reference systems"): one "global" chart for describing the overall dynamics of the $N$ bodies, and $N$ "local" charts adapted to the separate description of the structure and environment of each body. The main tool which allows us to develop, in an elegant manner, a constructive theory of these $N+1$ reference systems is a systematic use of a particular "exponential" parametrization of the metric tensor which has the effect of linearizing both the field equations, and the transformation laws under a change of reference system. This linearity allows a treatment of the first post-Newtonian relativistic celestial mechanics which is, from a structural point of view, nearly as simple and transparent as its Newtonian analogue. Our scheme differs from previous attempts in several other respects: the structure of the stress-energy tensor is left completely open; the spatial coordinate grid (in each system) is fixed by algebraic conditions while a convenient "gauge" flexibility is left open in the time coordinate [at the order $\ensuremath{\delta}t=O({c}^{\ensuremath{-}4})$]; the gravitational field locally generated by each body is skeletonized by particular relativistic multipole moments recently introduced by Blanchet and Damour, while the external gravitational field experienced by each body is expanded in terms of a particular new set of relativistic tidal moments. In this first paper we lay the foundations of our formalism, with special emphasis on the definition and properties of the $N$ local reference systems, and on the general structure and transformation properties of the gravitational field. As an illustration of our approach we treat in detail the simple case where each body can, in some approximation, be considered as generating a spherically symmetric gravitational field. This "monopole truncation" leads us to a new (and, in our opinion, improved) derivation of the Lorentz-Droste-Einstein-Infeld-Hoffmann equations of motion. The detailed treatment of the relativistic motion of bodies endowed with arbitrary multipole structure will be the subject of subsequent publications.

The UDP glucuronosyltransferase gene superfamily: suggested nomenclature based on evolutionary divergence.

Abstract: A nomenclature system for the UDP glucuronosyltransferase superfamily is proposed, based on divergent evolution of the genes. A total of 26 distinct cDNAs in five mammalian species have been sequenced to date. Comparison of the deduced amino acid sequences leads to the definition of two families and a total of three subfamilies. For naming each gene, we propose that the root symbol UGT for human (Ugt for mouse), representing "UDP glucuronosyltransferase," be followed by an Arabic number denoting the family, a letter designating the subfamily, and an Arabic numeral representing the individual gene within the family or sub-family (hyphen before the Arabic number for mouse), e.g., human UGT2B1 and murine Ugt2b-1. Whereas the gene and cDNA should be italicized, the corresponding transcript, protein, and enzyme activity should not be written with lowercase letters or in italics, e.g., human or murine UGT2B1. Recent experimental evidence suggests that several exons of the UGT1 gene might be shared, ind...

The Pathogenesis of Chronic Renal Failure in Diabetic Nephropathy: Investigation of 488 Cases of Diabetic Glomerulosclerosis*

Abstract: Investigation of renal biopsy specimens from 488 patients with diabetic glomerulosclerosis (DGS) of varying severity revealed the following: 1) The severity of DGS increases with the duration of the diabetes. 2) As the severity of DGS increases, it is complicated with increasing frequency by exudative changes, which correspond in detail to hyperperfusion lesions described in the literature. 3) As the severity of DGS increases, the severity of arteriolosclerosis and the incidence of nephrotic syndrome increase significantly. 4) The 5- and 10-year renal survival rates are highest for those diabetic patients in whom the tubules and renal cortical interstitium are of normal appearance. These survival rates are diminished if any of the following are present at the time of biopsy: a) interstitial fibrosis; b) hyperperfusion lesions; c) nephrotic syndrome; d) elevation of the serum creatinine concentration to more than 1.3 mg%. 5) No significant correlation was found between renal survival rate and age, sex, or type of diabetes. 6) The inflammation of the renal interstitium seen in diabetes does not differ from that seen in chronic glomerulonephritis. Monocytes, macrophages, T lymphocytes, fibroblasts and fibrocytes play the major role in this inflammation. This inflammatory process is considered to represent not pyelonephritis, but rather an auto-immune process. In other words, it is proposed that the diabetic kidney fails not only as a result of non-specific glomerular lesions (hyperperfusion lesions) but also because of non-specific tubulointerstitial changes, whereas diabetic glomerulosclerosis alone does not lead to chronic renal failure.

The AMPA receptor antagonist NBQX has antiparkinsonian effects in monoamine-depleted rats and MPTP-treated monkeys.

Abstract: Abnormally increased subthalamic nucleus output to the internal pallidal segment and the reticular part of the substantia nigra plays a critical pathophysiological role in the development of parkinsonism. Because synaptic transmission of subthalamic output is glutamatergic and mediated, in part, by the alpha-amino-3-hydroxy-5-methyl-4-isoxazole propionate (AMPA) subtype of glutamate receptor, AMPA receptor antagonists may possess antiparkinsonian properties. We report that in monoamine-depleted rats, 2,3-dihydroxy-6-nitro-7-sulfamoyl-benzo(f)quinoxaline (NBQX) (Novo-Nordisk, Copenhagen, Denmark)--a selective antagonist of the AMPA subtype of glutamate receptor--suppressed muscular rigidity but had no effect on akinesia. NBQX microinjected into the subthalamic nucleus, internal pallidal segment, and reticular part of the substantia nigra, but not into the laterodorsal neostriatum of the rats, stimulated locomotor activity and reduced muscular rigidity. In aged Rhesus monkeys with bilateral 1-methyl-4-phenyl-1,2,3,6-tetrahydropyridine-induced parkinsonism, intramuscular NBQX produced clinically apparent improvement in akinesia, tremor, posture, and gross motor skills. NBQX also potentiated the antiparkinsonian effects of L-3,4-dihydroxyphenylalanine in both rats and monkeys. Blockade of excitatory synaptic transmission by AMPA receptor antagonists may provide a new therapeutic strategy for Parkinson's disease (PD).

Conductance, work function and catalytic activity of SnO2-based gas sensors

Abstract: We have studied the geometric microstructure as well as the elemental composition and distribution of SnO2-based polycrystalline sensors with X-ray diffraction and surface spectroscopic techniques. Electrical properties and responses against reducing gases are characterized by a.c. and d.c. measurements of resistances and/or conductances. The models explaining the high sensitivity of polycrystalline SnO2 against reducing gases in terms of changes of the intergrain conductivity have been completed. The Schottky-barrier mechanism of the electron transport across the grain boundaries is valid only for SnO2 grains larger than the Debye length of electrons. For grains smaller than the Debye length, the band bending at the surface can be neglected compared with the overall shift of the Fermi level in the grains during gas exposure. From combined measurements of conductances, work function changes and catalytic activities as functions of temperature, CO and H2O partial pressures, we deduce that OH dipoles, which do not influence the oxidation kinetics of carbon monoxide, are formed during interaction with water at 673 K.

Articulatory deficits in parkinsonian dysarthria: an acoustic analysis.

Abstract: Twelve patients with idiopathic Parkinson's disease had acoustic speech analysis of sentence utterances to provide information on speech tempo and accuracy of articulation. As a measure of rate of speech the duration of opening-closing movements during articulation was determined from speech wave variables. The intensity of sound emission during articulatory closure as required for stop consonant production, for example, magnitude of p, magnitude of t, magnitude of k, was used as an index of the degree of closure. Speech tempo was not significantly different from normal. The patients, however, had a reduced capacity of completing articulatory occlusion. This was interpreted as reflecting a reduction in movement amplitude of the articulators. Articulatory "undershoot" was not uniform but influenced by linguistic demands in that the closures associated with a stressed syllable were performed at the expense of unstressed ones. Furthermore, switching between opening and closing movements of the articulators in sentence production seemed undisturbed. These results indicate that motor planning of speech differs from arm movement control.

Topography of projections from the auditory cortex to the inferior colliculus in the rat.

Abstract: We examined the organization of descending projections from auditory and adjacent cortical areas to the inferior colliculus (IC) in the rat by using the retrograde and anterograde transport of wheat germ agglutinin-horseradish peroxidase. Small tracer injections were placed into cytologically defined subnuclei of the IC. On the basis of the resulting pattern of retrogradely labeled neurons in the cortex, different cortical areas and fields were defined. Two secondary areas located ventrocaudally (Te2) and ventrally (Te3) to the primary auditory area (Te1) were delineated. The primary auditory area was subdivided into a posterior (Te1.p), a medial (Te1.m), and an anterior (Te1.a) auditory field. In addition, we outlined an area located rostrally to the auditory areas comprising a part of the secondary somatosensory cortex, as well as a dorsal belt surrounding dorsally the auditory areas. The following basic patterns of corticocollicular projections are revealed: (1) layers 2 and 3 of the dorsal cortex of the IC (DC2, DC3) are differentially innervated by the primary auditory fields (Te1.p and Te1.a project bilaterally to DC2, while Te1.m projects bilaterally and in topographical order to DC3); cells in Te1.m, arranged in caudal to rostral sequence, project to corresponding loci in DC3 arranged from dorsolateral to ventromedial; (2) the fibrocellular capsule of the IC, comprising layer 1 of the dorsal and external cortex of the IC, receives input from the secondary auditory area Te2; (3) layers 2 and 3 of the external cortex of the IC are only weakly innervated by the primary and secondary auditory cortex; (4) the intercollicular zone receives its major input from the secondary auditory area Te3, the secondary somatosensory cortex, and the dorsal belt; and (5) finally, the central nucleus of the IC receives no input from the temporal cortex at all. Our results demonstrate that the corticocollicular projections are highly organized. These pathways may modulate auditory processing in different functional circuits of the inferior colliculus.

Inhibition of leukotriene B4 formation in rat peritoneal neutrophils by an ethanolic extract of the gum resin exudate of Boswellia serrata.

Abstract: Suspensions of rat peritoneal polymorphonuclear leukocytes (PMNL) elicited with glycogen were stimulated by calcium and ionophore to produce leukotrienes and 5-HETE from endogenous arachidonic acid (AA). We investigated the effect of ethanolic extracts of the gum resin exudate of Boswellia serrata. A concentration-dependent inhibition of LTB4 and 5-HETE production by different charges of exudate extracts were found. All products of the 5-lipoxygenase (5-LOx) from endogenous arachidonic acid (AA) in PMNL were reduced to the same extent by the extracts tested. The ethanolic extract of the gum resin also decreased 5-LOx mediated metabolisation of exogenously added AA to LTB4 and 5-HETE. Since steroidal-type anti-inflammatory drugs do not exert an immediate effect in the test system used, we conclude that the activity of the 5-LOx itself represents the side of inhibition by the gum resin extract. Therefore, an inhibition of 5-LOx catalysed mediator synthesis might be involved in the previously reported anti-inflammatory activity in vivo.

Zeta potential measurements of Ta2O5 and SiO2 thin films

Abstract: Flat-plate streaming potential measurements were carried out on samples of tantalum pentoxide and silicon dioxide. The Ta2O5 samples were 150 nm films on silicon substrates, fabricated by the deposition of tantalum followed by oxidation in pure oxygen at 550°C. The SiO2 samples were 1 μm thick films prepared by steam oxidation of a silicon substrate. The electrolyte used in the measurements was NaCl, at concentrations of 10−1, 10−2, and 10−3 M. The point of zero zeta potential (pHiep) was between 2.7 and 3.0 for the Ta2O5 samples and between 2.6 and 3.2 for SiO2. In both cases, this agrees well with previous literature determinations, and indicates the reliability of the flat-plate method. We observed that the zeta potential of thin films of Ta2O5 was more stable and had less hysteresis than the zeta potential of thin SiO2 films.

Schottky-barrier and conductivity gas sensors based upon Pd/SnO2 and Pt/TiO2

Abstract: Electronic conductivity, mixed conductivity and Schottky-barrier sensors based upon the oxides SnO2 and TiO2 which are modified or contacted by the metals Pd and Pt can be used to detect gases like CO, CH4, H2 and O2. The response signals of these different types of sensors result from changes in surface and bulk conductivities or in Schottky-barrier heights, which are measured using different geometric arrangements of metal (Pd or Pt) contacts. The atomistic understanding of sensing mechanisms and corresponding sensor structures is deduced from comparative spectroscopic and electrical measurements. Our studies show that reliable sensor properties can only be achieved either by forming stable metal/oxide interfaces or by adjusting a stable dopant distribution.

Does "grief work" work?

Abstract: This article challenges the long-standing belief in the necessity of "grief work" for adjustment to bereavement. Evidence is offered from a prospective study of 30 widows and 30 widowers that indicates that grief work is not always as essential for adjustment to bereavement as theorists and clinicians have claimed. Widows who avoided confronting their loss did not differ in their depression scores from widows who worked through their grief. However, for widowers, performance of grief work was associated with better adjustment over an 18-month period. The implications of these findings for the grief work hypothesis are considered.

Metabolic and destructive brain disorders in children: findings with localized proton MR spectroscopy.

Abstract: The diagnostic potential of volume-selective proton magnetic resonance (MR) spectroscopy in vivo was evaluated in 20 children and young adults with various neurodegenerative brain disorders. All patients were examined with MR spectroscopy in conjunction with MR imaging of the brain on a whole-body imager at 1.5 T. Comparison of spectra in our patients with those of children with normal myelination (prominent signals from N-acetylaspartate [NAA], creatine/phosphocreatine, and choline) revealed a marked decrease of NAA in 12 of 17 patients with focal or generalized demyelination. In patients with Canavan disease, NAA signal intensity was markedly increased, but no choline signal was found. Increased signal intensity from lactate occurred in patients with Leigh disease, neuroaxonal dystrophy, Schilder disease, and Cockayne disease, which indicated a disturbed energy metabolism in the examined region. These results demonstrate that proton MR spectroscopy can be applied in a clinical environment to facilitate diagnosis of hereditary and acquired brain disorders in children.

The Relationship of Microglial Cells to Dying Neurons During Natural Neuronal Cell Death and Axotomy-induced Degeneration of the Rat Retina

Abstract: The interactions between dying neurons and phagocytotic cells within the developing and injured retina remain controversial. The present work explored the role of microglia and investigated whether so-called resident microglial cells are permanently responsible for removing cell debris whenever it is produced. As a first goal, I characterized some quantitative and morphometric features of the small ipsilateral retinocollicular projections and analysed the permanent function of phagocytosing microglia with these projections as a paradigm. To achieve this, I combined the fluorescent dyes Dil and 4Di-10ASP, both of which persist in the labelled ganglion cells after injection into the superior colliculus (SC), and retrograde labelling. After neuronal degradation, the dyes accompany the degradation products, become interiorized and then persist within the phagocytosing microglia. Consequently, early labelling of microglial cells can be assessed by injecting one dye into the SC during the first postnatal day of life, that is, prior to advanced natural neuronal cell death. Labelling of the remaining ipsilaterally projecting neurons with the second dye following intraorbital axotomy in adulthood and during subsequent neuronal death would therefore result in double labelling of some microglial cells, if these were involved in phagocytosis during both the natural and the induced phases of neuronal degradation. The ganglion cells which survived natural neuronal cell death remained fluorescent for 3 months after labelling with either dye on the day of the animal's birth, indicating that both fluorescent probes persisted within neurons. Quantitatively, 1770+/-220 ganglion cells/mm2 were labelled within the contralateral retina and a total population of 1442+/-120 cells/retina were observed within the periphery of the inferior/temporal quadrant of the ipsilateral retina. A smaller, ipsilateral projection of 150+/-24 cells/retina was uniformly scattered throughout the rest of the retinal surface. Transient projections of ganglion cells to either the contralateral or the ipsilateral colliculi and death of labelled ganglion cells during the first postnatal days resulted in labelling of 210+/-36 microglial cells/mm2 within the contralateral retina and a total number of 800+/-120 cells/retina within the inferior/temporal and 200+/-22 cells/retina within the rest of the retina. These labelled microglial cells were observed in adulthood and indicated that after taking away the neuronal cell debris they persisted within the retinal tissue. The small number of prelabelled ganglion cells which formed persistent ipsilateral projections until adulthood were axotomized by transecting the optic nerve, and resulted in additional labelling of microglial cells with the second fluorescent dye as well. Double-labelled microglia were observed within the inferior/temporal quadrant (3500+/-240 cells/retina) and to a lesser extent (340+/-40 cells/retina) scattered over the entire retinal surface. The chronotopological sequence of microglial labelling paralleled that of ganglion cell degeneration. Injection of protease inhibitors into the vitreous body during optic nerve transection retarded retrograde glial cell degeneration, probably by blocking microglial proteases. The results directly proved that the same microglial cells which remove neuronal cell debris in the postnatal retina were reactivated later in life to proteolytically degrade and then phagocytose neurons which had altered because of the axotomy.

Transport processes and noise in YBa2Cu3O7−δ grain boundary junctions

Abstract: In the high temperature superconductors the weak link nature of extended defects as grain boundaries is responsible for the deterioration of the superconducting transport properties. From the study of individual grain boundaries in thin-film bicrystals of YBa2Cu3O7−δ general relations describing the superconducting transport and noise characteristics of grain boundaries in the high temperature superconductors were found. Firstly, the critical current density Jgbc decreases as the misorientation angle between the adjoining grains increases. Secondly, the Jgbc ϱN products, where ϱN is the normal resistance times unit area of the grain boundaries, scale proportional to about (1/ϱN)q with q ranging between 1 and 1.5. Thirdly, all grain boundaries show large amounts of low frequency 1/f noise. The transport and noise characteristics can be explained by a junction model which is based on an insulating layer at the grain boundary interface containing a large number of localized defect states.

A neuronal correlate of spatial stability during periods of self-induced visual motion

Abstract: Motion of background visual images across the retina during slow tracking eye movements is usually not consciously perceived so long as the retinal image motion results entirely from the voluntary slow eye movement (otherwise the surround would appear to move during pursuit eye movements). To address the question of where in the brain such filtering might occur, the responses of cells in 3 visuo-cortical areas of macaque monkeys were compared when retinal image motion of background images was caused by object motion as opposed to a pursuit eye movement. While almost all cells in areas V4 and MT responded indiscriminately to retinal image motion arising from any source, most of those recorded in the dorsal zone of area MST (MSTd), as well as a smaller proportion in lateral MST (MST1), responded preferentially to externally-induced motion and only weakly or not at all to self-induced visual motion. Such cells preserve visuo-spatial stability during low-velocity voluntary eye movements and could contribute to the process of providing consistent spatial orientation regardless of whether the eyes are moving or stationary.

Efficiency of peptides and lipopeptides for in vivo priming of virus-specific cytotoxic T cells.

Abstract: Synthetic peptides and a novel type of lipopeptide vaccine, both containing T cell epitopes recognized by Kd-restricted, influenza virus-specific cytotoxic T cells (CTL) were compared in their efficiency to induce virus-specific CTL in vivo. All attempts to induce virus-specific CTL with synthetic peptide (in the absence of adjuvants) failed. However, a latent immunization was observed, resulting in an increased response to the injected peptide seen only after boosting the recipients with immunogenic virus. In contrast, priming with synthetic lipopeptide vaccine (tripalmitoyl-S-glycerylcysteinyl-seryl-serine [P3CSS] coupled to peptide) was successful under most conditions, and matched the priming efficiency seen with infectious virus. The requirements for in vivo priming of virus-specific CTL using lipopeptide suggest that attachment of the lipopeptide to a hydrophobic entity, such as the cell membrane, is responsible for its efficiency.

Anaerobic aniline degradation via reductive deamination of 4-aminobenzoyl-coa in desulfobacterium anilini

Abstract: The initial reactions involved in anaerobic aniline degradation by the sulfate-reducing Desulfobacterium anilini were studied. Experiments for substrate induction indicated the presence of a common pathway for aniline and 4-aminobenzoate, different from that for degradation of 2-aminobenzoate, 2-hydroxybenzoate, 4-hydroxybenzoate, or phenol. Degradation of aniline by dense cell suspensions depended on CO2 whereas 4-aminobenzoate degradation did not. If acetyl-CoA oxidation was inhibited by cyanide, benzoate accumulated during degradation of aniline or 4-aminobenzoate, indicating an initial carboxylation of aniline to 4-aminobenzoate, and further degradation via benzoate of both substrates. Extracts of alinine or 4-aminobenzoategrown cells activated 4-aminobenzoate to 4-aminobenzoyl-CoA in the presence of CoA, ATP and Mg2+. 4-Aminobenzoyl-CoA-synthetase showed a Km for 4-aminobenzoate lower than 10 μM and an activity of 15.8 nmol · min-1 · mg-1. 4-Aminobenzoyl-CoA was reductively deaminated to benzoyl-CoA by cell extracts in the presence of low-potential electron donors such as titanium citrate or cobalt sepulchrate (2.1 nmol · min-1 · mg-1). Lower activities for the reductive deamination were measured with NADH or NADPH. Reductive deamination was also indicated by benzoate accumulation during 4-aminobenzoate degradation in cell suspensions under sulfate limitation. The results provide evidence that aniline is degraded via carboxylation to 4-aminobenzoate, which is activated to 4-aminobenzoyl-CoA and further metabolized by reductive deamination to benzoyl-CoA.

A survey of spiral-wave behaviors in the oregonator model

Abstract: We carried out a numerical exploration of spiral waves in a typical excitable medium, emphasizing the variety of behaviors encountered while changing two parameters of local excitability: the threshold for starting an excitation and the excitation rate at the wavefront. Within this parameter plane we found domains in which: 1) propagation is impossible, 2) propagation succeeds but there are no spiral waves, 3) spiral waves are stable and strictly periodic, 4) spiral waves exhibit two-period quasiperiodicity, and 5) spiral waves exhibit complex behavior that might be associated with the well-known instability of three-period flows on the three-torus. The boundary curves (bifurcation loci) separating these domains run parallel to the propagation boundary over much of their extent.