Showing papers by "Michael Meyer published in 1997"

Ataxia and altered dendritic calcium signaling in mice carrying a targeted null mutation of the calbindin D28k gene

Abstract: Intracellular calcium-binding proteins are abundantly expressed in many neuronal populations. Previous evidence suggests that calcium-binding proteins can modulate various neuronal properties, presumably by their action as calcium buffers. The importance of calcium-binding proteins for nervous system function in an intact integrated system is, however, less clear. To investigate the physiological role of a major endogenous calcium-binding protein, calbindin D28k (calbindin) in vivo, we have generated calbindin null mutant mice by gene targeting. Surprisingly, calbindin deficiency does not affect general parameters of development and behavior or the structure of the nervous system at the light microscopic level. Null mutants are, however, severely impaired in tests of motor coordination, suggesting functional deficits in cerebellar pathways. Purkinje neurons, the only efferent of the cerebellar cortex, and inferior olive neurons, the source of the climbing fiber afferent, have previously been shown to express calbindin. Correlated with this unusual type of ataxia, confocal calcium imaging of Purkinje cells in cerebellar slices revealed marked changes of synaptically evoked postsynaptic calcium transients. Their fast, but not their slow, decay component had larger amplitudes in null mutant than in wild-type mice. We conclude that endogenous calbindin is of crucial importance for integrated nervous system function.

Interaction of Bartonella henselae with endothelial cells results in bacterial aggregation on the cell surface and the subsequent engulfment and internalisation of the bacterial aggregate by a unique structure, the invasome

Abstract: Vascular colonisation by Bartonella henselae may cause vaso-proliferative tumour growth with clumps of bacteria found in close association with proliferating endothelial cells. By using B. henselae-infected human umbilical vein endothelial cells as an in vitro model for endothelial colonisation, we report here on a novel mechanism of cellular invasion by bacteria. First, the leading lamella of endothelial cells establishes cellular contact to sedimented bacteria and mediates bacterial aggregation by rearward transport on the cell surface. Subsequently, the formed bacterial aggregate is engulfed and internalised by a unique host cellular structure, the invasome. Completion of this sequence of events requires 24 hours. Cortical F-actin, intercellular adhesion molecule-1 and phosphotyrosine are highly enriched in the membrane protrusions entrapping the bacterial aggregate. Actin stress fibres, which are anchored to the numerous focal adhesion plaques associated with the invasome structure, are typically found to be twisted around its basal part. The formation of invasomes was found to be inhibited by cytochalasin D but virtually unaffected by nocodazole, colchicine or taxol, indicating that invasome-mediated invasion is an actin-dependent and microtubuli-independent process. Bacterial internalisation via the invasome was consistently observed with several clinical isolates of B. henselae, while a spontaneous mutant obtained from one of these isolates was impaired in invasome-mediated invasion. Instead, this mutant showed increased uptake of bacteria into perinuclear localising phagosomes, suggesting that invasome-formation may interfere with this alternative mechanism of bacterial internalisation. Internalisation via the invasome represents a novel paradigm for the invasion of bacteria into host cells which may serve as a cellular colonisation mechanism in vivo, e.g. on proliferating and migrating endothelial cells during Bartonella-induced vaso-proliferative tumour growth.

Vulnerability of midbrain dopaminergic neurons in calbindin-D28k-deficient mice: lack of evidence for a neuroprotective role of endogenous calbindin in MPTP-treated and weaver mice.

Abstract: Calbindin-D28k (calbindin) is an intracellular calcium binding protein of unknown in vivo function. It is abundantly expressed in many populations of neurons, and it can, presumably by buffering calcium overload, protect cells against excitotoxic damage. In the midbrain, calbindin is preferentially expressed in those dopamine neurons which are spared from degeneration in Parkinson's disease and its animal models. Whether calbindin itself determines neuronal vulnerability is questioned in other lesion models where calbindin expression is not positively correlated with neuronal resistance. To study the possible neuroprotective role of calbindin in vivo, we generated calbindin-deficient mice by gene targeting and assessed the viability of midbrain dopamine neurons in both a chemical and a genetic lesion paradigm. Tyrosine hydroxylase-immunoreactive neurons were counted in calbindin null-mutant mice treated with the neurotoxin 1-methyl-4-phenyl-1,2,3,6-tetrahydropyridine (MPTP) and in a calbindin-deficient weaver strain (homozygous for weaver and the calbindin null mutation). The extent and pattern of neuron loss observed in MPTP-treated wild-type and homozygous weaver mice were as previously described. Surprisingly, no significant differences were observed between MPTP-treated calbindin null mutants and their wild-type littermates, or between calbindin-weaver double mutant mice and weaver mice. Thus, in all four groups the same subpopulation of tyrosine hydroxylase-positive midbrain neurons (i.e. those normally containing calbindin) were preferentially spared. Calretinin, a closely related calcium-binding protein, which is also expressed in some midbrain dopamine neurons, was not up-regulated in these surviving neurons. These findings indicate that the resistance of calbindin-containing neurons in the MPTP and weaver models is not causally related to the expression of calbindin, and that endogenous calbindin is not required for protection of these neurons.

Gas exchange and cardiovascular kinetics with different exercise protocols in heart transplant recipients

Abstract: Grassi, Bruno, Claudio Marconi, Michael Meyer, Michel Rieu, and Paolo Cerretelli. Gas exchange and cardiovascular kinetics with different exercise protocols in heart transplant recipients.J. Appl. ...

The Transitional Pre--Main-Sequence Object DI Tauri: Evidence for a Substellar Companion and Rapid Disk Evolution

Abstract: We report mid-IR observations of two young stars found in the Taurus dark cloud, spatially resolving for the first time their 10 μm emission. The weak-emission T Tauri star DI Tau, tentatively identified by Skrutskie et al. on the basis of 12 μm IRAS data as an object in the process of dissipating its circumstellar disk, is found to have no infrared excess at a wavelength of 10 μm. The nearby classical T Tauri star DH Tau exhibits excess emission at 10 μm consistent with predictions based on circumstellar disk models. While both objects appear to have the same stellar mass, age, and rotation rate, they differ in two fundamental respects: DH Tau is a single star with an active accretion disk, and DI Tau is a binary system lacking such a disk. The companion to DI Tau has a very low luminosity and is located at a projected distance of ~20 AU from the primary. Assuming the system to be coeval, we derive a mass below the hydrogen burning limit for the companion. We speculate that the formation of a substellar mass companion has led to the rapid evolution of the circumstellar disk that may have surrounded DI Tau.

Magnetospheric accretion and PMS stellar masses

Abstract: We present a method of determining lower limits on the masses of pre-main-sequence (PMS) stars and so constraining the PMS evolutionary tracks. This method uses the red-shifted absorption feature observed in some emission-line profiles of T Tauri stars indicative of infall. The maximum velocity of the accreting material measures the potential energy at the stellar surface, which, combined with an observational determination of the stellar radius, yields the stellar mass. This estimate is a lower limit owing to uncertainties in the geometry and projection effects. Using available data, we show that the computed lower limits can be larger than the masses derived from PMS evolutionary tracks for M < 0.5M⊙. Our analysis also supports the notion that accretion streams do not impact near the stellar poles but probably hit the stellar surface at moderate latitudes.

The Transitional PMS Object DI Tauri: Evidence for a Sub-stellar Companion and Rapid Disk Evolution

Abstract: We report mid--IR observations of two young stars found in the Taurus dark cloud spatially resolving for the first time their 10 $\mu$m emission The weak-emission T Tauri star DI Tau, tentatively identified by Skrutskie et al (1990) on the basis of 12 $\mu$m IRAS data as an object in the process of dissipating its circumstellar disk, is found to have no infrared excess at a wavelength of 10 $\mu$m The nearby classical T Tauri star DH Tau exhibits excess emission at 10 $\mu$m consistent with predictions based on circumstellar disk models While both objects appear to have the same stellar mass, age, and rotation rate, they differ in two fundamental respects: DH Tau is a single star with an active accretion disk and DI Tau is a binary system lacking such a disk The companion to DI Tau has a very low luminosity and is located at a projected distance of $\sim 20$ AU from the primary Assuming the system to be co-eval, we derive a mass below the hydrogen burning limit for the companion We speculate that the formation of a sub-stellar mass companion has led to the rapid evolution of the circumstellar disk that may have surrounded DI Tau