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Biomedical subjects

M Barth

Publications and source records attributed to M Barth.

At least 37 records · Page 2Linked to original sources

Endothelin b receptor deficiency is associated with an increased rate of neuronal apoptosis in the dentate gyrus.

The dentate gyrus retains neuronal proliferative potential throughout life. Using immature endothelin B receptor-deficient (sl/sl) rats, a rabbit model of pneumococcal meningitis and autopsy brains from humans who died from pneumococcal meningitis, we explored the role of endothelin B receptors in physiological and pathological neuronal apoptosis in the dentate gyrus. At postnatal days 3-4, the rate of apoptosis in the dentate gyrus was high in all rats, declining to low levels in wild-type rats (+/+) on days 14 and 22, but remaining high in both homozygous (sl/sl) and heterozygous (sl/+) endothelin B receptor-deficient rats. Increased apoptosis was not significantly compensated for by neuronal proliferation. Hippocampal neuronal cultures also exhibited genotype-dependent apoptosis with the highest rate in neurons from homozygous endothelin B receptor-deficient (sl/sl) rats. In rabbit and human pneumococcal meningitis, increased apoptosis in the dentate gyrus was associated with loss of neuronal endothelin B receptor immunoreactivity. In conclusion, endothelin B receptors appear to act as neuronal survival factors in the dentate gyrus in rodents and man, both during postnatal development and under pathological conditions.

Aging↗

Interaction of temperature, humidity, driver preferences, and refrigerant type on air conditioning compressor usage.

Recent studies have shown large increases in vehicle emissions when the air conditioner (AC) compressor is engaged. Factors that affect the compressor-on percentage can have a significant impact on vehicle emissions and can also lead to prediction errors in current emissions models if not accounted for properly. During 1996 and 1997, the University of California, Riverside, College of Engineering-Center for Environmental Research and Technology (CE-CERT) conducted a vehicle activity study for the California Air Resources Board (CARB) in the Sacramento, CA, region. The vehicles were randomly selected from all registered vehicles in the region. As part of this study, ten vehicles were instrumented to collect AC compressor on/off data on a second-by-second basis in the summer of 1997. Temperature and humidity data were obtained and averaged on an hourly basis. The ten drivers were asked to complete a short survey about AC operational preferences. This paper examines the effects of temperature, humidity, refrigerant type, and driver preferences on air conditioning compressor activity. Overall, AC was in use in 69.1% of the trips monitored. The compressor was on an average of 64% of the time during the trips. The personal preference settings had a significant effect on the AC compressor-on percentage but did not interact with temperature. The refrigerant types, however, exhibited a differential response across temperature, which may necessitate separate modeling of the R12 refrigerant-equipped vehicles from the R134A-equipped vehicles. It should be noted that some older vehicles do get retrofitted with new compressors that use R134A; however, none of the vehicles in this study had been retrofitted.

Air Conditioning↗

Autocorrelation function of level velocities for ray-splitting billiards

We study experimentally and theoretically the autocorrelation function of level velocities c(x) and the generalized conductance C(0) for classically chaotic ray-splitting systems. Experimentally, a Sinai ray-splitting billiard was simulated by a thin microwave rectangular cavity with a quarter-circle Teflon insert. For the theoretical estimates of the autocorrelator c(x) and the conductance C(0) we made parameter-dependent quantum calculations of eigenenergies of an annular ray-splitting billiard. Our experimental and numerical results are compared to theoretical predictions of systems based on the Gaussian orthogonal ensemble in random matrix theory.

Journal Article↗

An invasion-related complex of cortactin, paxillin and PKCmu associates with invadopodia at sites of extracellular matrix degradation.

Invasive breast cancer cells have the ability to extend membrane protrusions, invadopodia, into the extracellular matrix (ECM). These structures are associated with sites of active matrix degradation. The amount of matrix degradation associated with the activity of these membrane protrusions has been shown to directly correlate with invasive potential. We demonstrate here that microinjection of polyclonal anti-cortactin antibodies blocks matrix degradation at invadopodia supporting the hypothesis that cortactin has a direct role in invasive behavior. MDA-MB-231, invasive breast cancer cells were sheared from the surface of a gelatin matrix to isolate invadopodia. Cortactin, paxillin and protein kinase C (PKC) mu, a serine kinase, were co-immunoprecipitated as a complex from invadopodia-enriched membranes. We confirmed the subcellular distribution of these proteins by immunolocalization and Western blotting. We also determined that, in contrast to its presence in invasive cells, this complex of proteins was not detected in lysates from non-invasive cells that do not form invadopodia. Taken together, these data suggest that the formation of this cortactin-containing complex correlates with cellular invasiveness. We hypothesize that this complex of molecules has a role in the formation and function of invadopodia during cellular invasion.

Actins↗

High-resolution, multiple gradient-echo functional MRI at 1.5 T.

A multiple gradient echo, high resolution imaging method is proposed to better visualize different sources of activation in functional magnetic resonance imaging (fMRI) experiments. Eight echoes are collected from 30 ms to 205 ms with an echo spacing of 25 ms. All echoes show significant activation, but each echo reveals its own pattern of activation. From this variability, it appears that large vessel contributions can be separated from small vessel contributions using a fuzzy cluster analysis across echo times. The results demonstrate the importance of a multiple gradient echo data acquisition approach in localizing various vascular contributions to brain activation in fMRI.

Adult↗

Functional MRI of the human motor cortex using single-shot, multiple gradient-echo spiral imaging.

In this study, we combined the advantages of a fast multi-slice spiral imaging approach with a multiple gradient-echo sampling scheme at high magnetic field strength to improve quantification of BOLD and inflow effects and to estimate T2* relaxation times in functional brain imaging. Eight echoes are collected with echo time (TE) ranging from 5 to 180 ms. Acquisition time per slice and echo time is 25 ms for a nominal resolution of 4 x 4 x 4 mm3. Evaluation of parameter images during rest and stimulation yields no significant activation on the inflow sensitive spin-density images (rho or I0-maps) whereas clear activation patterns in primary human motor cortex (M1) and supplementary motor area (SMA) are detected on BOLD sensitive T2*-maps. The calculation of relaxation times and rates of the activated areas over all subjects yields an average T2* +/- standard deviation (SD) of 46.1+/-4.5 ms (R2* of 21.8+/-2.2 s(-1)) and an average increase (deltaT2* +/- SD) of 0.93+/-0.47 ms (deltaR2* of -0.4+/-0.14 s(-1)). Our findings demonstrate the usefulness of a multiple gradient echo data acquisition approach in separating various vascular contributions to brain activation in fMRI.

Adult↗

Experience-dependent development of the adult optic lobe and central brain in Drosophila melanogaster.

The optic lobes, mushroom bodies (MB) and central complex (CC) of Drosophila melanogaster were investigated in order to find out whether rearing in different light regimes affect their size. Flies raised in constant light up for up to four days post eclosion had a lamina that was about 30% larger than in flies kept in constant darkness. A volume difference between light- and dark-reared flies could also be observed for the lobula plate, the MBs, and the CC. When the flies were kept in the dark for the first 12 hours of their adult life and then brought back to constant light for the next 3.5 days, the lamina was as small as the laminae of flies raised for four days in constant darkness. This finding suggests a critical period for lamina development during day one of the imago. Mutant studies suggest that the molecular mechanisms underlying this experience-dependent development might be quite diverse. For example, the structural plasticity of the mushroom bodies is abolished in the dunce mutation, whereas the light-dependent growth of the lamina is not. Finally, studies of optomotor behavior indicate an adaptational role for the structural plasticity in the optic lobe. Surprisingly, dark-reared flies see better under low light conditions than their light-reared counterparts. This suggests that a small lamina is not a bad lamina in the sense that dark-reared animals see worse. They rather adapt to the specific light-conditions they were growing up in.

Aging↗

Delayed loss of ETB receptor-mediated vasorelaxation after cold lesion of the rat parietal cortex.

The aim of this study was to investigate the involvement of endothelins (ET) in brain injury. The effect of ET was studied in the isolated basilar artery (BA) taken from control, sham-operated, and cold-lesioned rats. Cold lesion was induced by application of a precooled (-78 degrees C) copper cylinder (outer diameter 5 mm) for 60 seconds to the intact dura over the parietal cortex. After precontraction with prostaglandin (PG) F2alpha, ET-3 (10(-10) to 10(-8) mol/L) dilated BA with a pD2 (negative log of the half-maximal concentration) of 9.06+/-0.031 (mean +/- SD) and a maximal effect (Emax) of 1.64+/-1.0 mN at 3 x 10(-9) mol/L in sham-operated animals. This dilation was reduced 24 and 48 hours after cold lesion by 33% and 73%, respectively, at 3 x 10(-9) mol/L. The effects of acetylcholine (10(-8) to 10(-4) mol/L) and sodium nitroprusside (10(-3) mol/L) were unaltered. Activation of the ETB receptor in thoracic aorta by the specific agonist IRL 1620 also resulted in a reduced dilation (51% by 48 hours after cold lesion). Reverse transcriptase-polymerase chain reaction of the BA showed unaltered expression of mRNA for the ETB receptor after cold lesion whereas ETB immunoreactivity in BA and in its intraparenchymal arteries was reduced at 24 and 48 hours. In contrast to the reduction of ET-3-induced dilation, the constrictor effects of ET-1 and ET-3 were retained after cold lesion. Endothelin-1 (10(-12) to 10(-6) mol/L) dose-dependently contracted segments of untreated control BA segments under resting conditions with a pD2 of 8.03+/-0.22 and an Emax of 6.35+/-0.70 mN. Further evidence that the constrictor ability of BA was not influenced by cold lesion is given by the unaltered response to 124 mmol/L K+ and 10(-6) mol/L serotonin. We conclude that the ETB receptor of BA after cold lesion is downregulated specifically, apparently at the posttranscriptional level. Because the ETB-mediated dilation in thoracic aorta was also reduced, downregulation of the ETB receptor apparently is not restricted to cerebral arteries. The nitric oxide-cyclic guanosine monophosphate system in BA is, however, intact.

Animals↗

Experience-dependent developmental plasticity in the optic lobe of Drosophila melanogaster.

Early experience can affect nervous system development in both vertebrate and invertebrate animals. We have now demonstrated that visual stimulation modifies the size of the optic lobes in the laboratory fruitfly Drosophila melanogaster. Monocular deprivation (painting over one eye) decreases the aggregate volume of the lamina, medulla, and lobula plate by up to 6%. The laminae of control flies kept in complete darkness showed a more robust volume difference that could be as much as 30%. An electron microscopy study revealed that the changes in the lamina are largely attributable to an increase in the terminals of the photoreceptor cell axons. The volume of the lamina increases during the first 24 hr after emergence, and it grows more in the light than in darkness. When flies are kept in the dark for the first 12 hr of their adult life and are then brought back to light for the next 3.5 days, the lamina is almost as small as in flies raised for 4 d in constant darkness. Twelve hour dark shifts at a later time are less effective. This finding suggests a critical period for lamina development during day 1 of the adult. The lamina depends on visual stimulation to maintain its size during the first 5 d after emergence. Dark-rearing for 1 d or more at any stage during that period decreases its volume to the level of flies raised in constant darkness. A lamina that is once reduced in size seems not to recover.

Animals↗

[MRI on low-field tomography systems (0.2 Tesla). A quantitative comparison with equipment of medium-field strength (1.0 Tesla)].

AIM OF THE STUDY: Using phantom studies, a dedicated low-field MR system with 0.2 T and a whole-body MR-scanner with 1.0 T were compared. METHODS: A spin-echo sequence was performed on the 0.2-T MR unit using the knee coil and on the 1.0-T MR unit with the head coil. In a water-filled phantom, signal-to-noise ratios (SNR) were calculated and contrast measurements on gels with well-defined relaxation times were obtained and compared to nominal relaxation times. Measurements of T1 and T2 relaxation times on the low-field system were compared to the 1.0-T unit. As a parameter for geometrical image quality, magnetic field distortions were calculated. In theory, influence of field strength and and receiver bandwidth on the minimal echo time and on chemical shift artifacts were calculated. RESULTS: The SNR was 63.2 on the 0.2-T and 179.6 on the 1.0-T MR unit (difference factor 3, against a theoretical difference of 5-16). Relaxation times on the low-field system were significantly (around 40-50%) lower. Measurements of contrast were similar on both systems. On the low-field system geometrical distortions of several pixels were recorded. The minimal echo time on the low-field system was 21.3 ms with the low receiver bandwidth and 4.3 ms on the 1.0-T MR unit. The amount of chemical shift artefacts was the same on both systems. DISCUSSION: On low-field MR systems SNR is markedly improved by small read-out gradients and a low receiver bandwidth (factor 3 vs 5-16 in comparison with the 1.0-T MR unit). However, an optimal homogeneous magnetic field is required, since inhomogeneities may create severe geometrical distortion.

Artifacts↗

Quantification of signal changes in gradient recalled echo FMRI.

Understanding and quantifying the various contributions to functional magnetic resonance imaging (FMRI) signal changes in activated cortical areas is paramount for a clinical application of brain mapping by FMRI. Therefore, all significant contributions to FMRI signal changes, both extra- and intravascular, from macrovessels down to the capillary network, should be taken into account. We present a gradient-recalled-echo FMRI model based on in-flow effects described by the Bloch equations, adding susceptibility effects empirically via T2* differences measured in vitro in human blood samples. Results of these calculations (by systematically varying alpha, echo time (TE), repetition time (TR), as well as blood velocity and T2* upon stimulation) may be used to (a) simulate functional MRI experiments with different measurement protocols and (b) estimate realistic values for important anatomical and physiological details that influence local signal changes in FMRI (i.e., size and distribution of vessels, effective relaxation times of blood, etc.). The excellent agreement between our model calculations and experimental results from conventional gradient recalled echo fMRI in vivo suggests a significant contribution from very slow flow and oxygenation changes, predominantly in small vessels (vblood = 1-4 mm/s). The actual contribution of T1- and T2-related effects is strongly dependent on sequence design and actual sequence parameters used. Thus, the model simulations presented may also be used to optimize measurement protocols for investigating various neurophysiological phenomena.

Adolescent↗

Modulation of signal changes in gradient-recalled echo functional MRI with increasing echo time correlate with model calculations.

Based on systematic in vivo studies analysed by fuzzy clustering, we prove the complex dependence of functional magnetic resonance imaging (fMRI) signal changes on echo time (TE) (ranging from 42 ms up to 160 ms) in the human visual cortex at 1.5 Tesla. We obtain a steady increase of signal enhancement with increasing TE, except at TE = 130 ms where the signal increase is significantly less than at 100 and 160 ms, respectively, caused by signal dephasing of spins in the vascular environment of the cortical region imaged. A comparison with model calculations reveals that vessels with a diameter of about 0.5 to 1 mm may be the main source of gradient-recalled echo fMRI signal changes at 1.5 Tesla at the given spatial resolution. In addition to conventional correlation analysis, fuzzy cluster analysis has been applied to evaluate fMRI data sets. Our results also indicate that, despite the similar temporal pattern of the functional response, it is possible to differentiate between areas which show higher signal enhancement (cluster 1, higher blood volume fraction) and lower signal enhancement (cluster 2, lower blood volume fraction), reflecting the different vascular environment. Therefore, fuzzy cluster analysis may help to extract functional information from activated areas closer to the actual neuronal activation.

Adolescent↗

Heat shock regulation of sigmaS turnover: a role for DnaK and relationship between stress responses mediated by sigmaS and sigma32 in Escherichia coli.

The cellular level of the rpoS-encoded sigmaS subunit of RNA polymerase increases in response to various stress situations that include starvation, high osmolarity, and shift to acid pH, and these different stress signals differentially affect rpoS translation and/or sigmaS stability. Here we demonstrate that sigmaS is also induced by heat shock and that this induction is exclusively due to an interference with sigmaS turnover. Some sigmaS-dependent genes exhibit similar heat shock induction, whereas others are not induced probably because they need additional regulatory factors that might not be present under conditions of heat shock or exponential growth. Despite its induction, sigmaS does not seem to contribute to heat adaptation but may induce cross-protection against different stresses. While sigmaS is not involved in the regulation of the heat shock sigma factor sigma32, the heat shock protein DnaK has a positive role in the posttranscriptional control of sigmaS. The present evidence suggests that DnaK is involved in the transduction of two of the signals that result in reduced sigmaS turnover, i.e., heat shock and carbon starvation. Heat shock induction of sigmaS also clearly indicates that a cessation of growth or even a reduction of the growth rate is not a prerequisite for the induction of sigmaS and sigmaS-dependent genes and underscores the importance of sigmaS as a general stress sigma factor.

Bacterial Proteins↗

Proton NMR relaxation times of human blood samples at 1.5 T and implications for functional MRI.

To further investigate the dependency of fMRI signal changes on echo time TE, we measured T2 and T2* values, obtained from human blood samples at various oxygenation levels and used them in a simple model to calculated signal enhancement in fMRI. In addition, the longitudinal relaxation time T1 of human blood was determined for reference. All measurements were performed at 23 degrees C to reduce blood cell metabolism during the measurement procedure. At 23 degrees C T1 values of 1434 +/- 48 ms for arterial human blood were obtained after correcting for hematocrit content, as hematocrit values ranged fro 28% to 34% only. The T2 relaxation times obtained are 181 +/- 23 ms for venous and 254 +/- 26 ms for arterial human blood, T2* relaxation times corrected for inhomogeneities of the static magnetic field (B0) are 42 +/- 2.8 ms and 254 +/- 32 ms, respectively. Furthermore, absolute and relative signal changes in fMRI experiments are calculated. The results from these model calculations reveal that contrast in fMRI can be optimised by choosing an appropriate echo time.

Adult↗

Role for the histone-like protein H-NS in growth phase-dependent and osmotic regulation of sigma S and many sigma S-dependent genes in Escherichia coli.

The sigma S subunit of RNA polymerase (encoded by the rpoS gene) is the master regulator in a complex regulatory network that controls stationary-phase induction and osmotic regulation of many genes in Escherichia coli. Here we demonstrate that the histone-like protein H-NS is also a component of this network, in which it functions as a global inhibitor of gene expression during the exponential phase of growth. On two-dimensional gels, at least 22 sigma S-controlled proteins show increased expression in an hns mutant. H-NS also inhibits the expression of sigma S itself by a mechanism that acts at the posttranscriptional level. Our results indicate that relief of repression by H-NS plays a role in stationary-phase induction as well as in hyperosmotic induction of rpoS translation. Whereas certain sigma S-dependent genes (e.g., osmY) are only indirectly regulated by H-NS via its role in the control of sigma S expression, others are also H-NS-regulated in a sigma S-independent manner. (For this latter class of genes, rpoS hns double mutants show higher levels of expression than mutants deficient in rpoS alone.) In addition, we demonstrate that the slow-growth phenotype of hns mutants is suppressed in hns rpoS double mutants and that many second-site suppressor mutants that spontaneously arise from hns strains carry lesions that affect the expression of sigma S.

Bacterial Outer Membrane Proteins↗