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Biomedical subjects

S Carlson

Publications and source records attributed to S Carlson.

At least 37 records · Page 2Linked to original sources

Recovery of locomotor function after treadmill training of incomplete spinal cord injured rats.

Our long-term goal is to formulate and assess functional methodologies to enhance recovery of locomotor function in human subjects after incomplete Spinal Cord Contusion Injury (iSCI). This methodology could consist of locomotor training by active treadmill walking. Here, we present kinematic analysis of limb movements in rats with iSCI that have undergone treadmill-walking training. Video images were recorded during treadmill walking of iSCI rats at different intervals from 2 weeks to 24 weeks post injury and in age matched rats without injury. A kinematic analysis program was used to acquire the data, which was further analyzed using Matlab routines. Joint angles were analyzed using cross-covariance and limit cycles. In addition, the maximum flexion and extension and range of motion (ROM) determined. 2 weeks post iSCI the ankle was overextended, the hip under flexed, and ROM of the knee severely reduced thereby leading to disoriented gait. The phase-shift between the hip and knee joints observed in uninjured rats during treadmill walking was absent in the iSCI rats. Treadmill training improved hip flexion and ankle overextension. Knee ROM continued to be deteriorated. The treadmill training eventually led to recovery of coordinated locomotor function after 7 weeks, albeit with deformities in gait. This recovery of locomotor function occurred in spite of significant loss of axonal connections between the brain and the spinal lumbar segments at site of injury (assessed by histology after terminal data collection). The results suggest that functional recovery of locomotion could be an activity dependent process.

Animals↗

Modulation of slow brain potentials by working memory load in spatial and nonspatial auditory tasks.

Slow event-related brain potentials were recorded from the human scalp during spatial and nonspatial auditory delayed matching-to-sample and n-back tasks to find out whether there are differences in the distribution of slow potentials during the retention of audiospatial and pitch information. The performance of both the location and pitch tasks produced slow potentials during the delay phase of the memory tasks. The delay-related slow potential was modulated by the amount of information to be processed during the tasks at the parietal-occipital sites. The distribution of mnemonic modulation was, however, not different between the tasks. The results suggest that there is integration of auditory information processing in the neuronal networks engaged in mnemonic processing of pitch and location.

Adolescent↗

Purkinje cell degeneration and control mice: responses of single units in the dorsal cochlear nucleus and the acoustic startle response.

The cartwheel cell is the most numerous inhibitory interneuron of the dorsal cochlear nucleus (DCN). It is expected to be an important determinant of DCN function. To assess the contribution of the cartwheel cell, we examined the discharge characteristics of DCN neurons and behavioral measures in the Purkinje cell degeneration (pcd) mice, which lack cartwheel cells, and compared them to those of the control mice. Distortion product otoacoustic emissions and auditory brainstem-evoked response thresholds were similar between the two groups. Extracellularly recorded DCN single units in ketamine/xylazine-anesthetized mice were classified according to post-stimulus time histogram (PSTH) and excitatory-inhibitory response area (EI-area) schemes. PSTHs recorded in mouse DCN included chopper, pauser/buildup, onset, inhibited and nondescript types. EI-areas recorded included Types I, II, III, I/III, IV and V. There were no significant differences in the proportions of various unit types between the pcd and control mice. The pcd units had slightly lower thresholds to characteristic frequency tones; however, they had spontaneous rates, thresholds to noise, and maximum driven rates to noise that were similar to those of the control units. Pcd mice had smaller startle amplitudes, but startle latency, prepulse inhibition/augmentation and facilitation by a background tone were comparable between the two groups. From these results, we conclude that DCN function in response to relatively simple acoustic stimuli is minimally affected by the absence of the cartwheel cells. Future studies employing more complex and/or multimodal stimuli should help assess the role of the cartwheel cells.

Acoustic Stimulation↗

Fear-potentiated startle, but not prepulse inhibition of startle, is impaired in CREBalphadelta-/- mutant mice.

Fear-potentiated startle was assessed in mice with a targeted disruption of the alpha and delta isoforms of the transcription factor cAMP response element binding protein (CREB) 24 hr after 5 tone + shock training trials. Whereas wild-type mice showed fear-potentiated startle that persisted up to 45 days after training, CREBalphadelta-/- mice failed to show fear-potentiated startle. However, CREBalphadelta-/- and wild-type mice had similar startle amplitudes and similar magnitudes of prepulse inhibition of startle, suggesting that CREBalphadelta-/- mice have no obvious sensory or motor deficits. These results add to the literature indicating that CREB-activated transcription plays a critical role in the formation of long-term memory and illustrate the utility of the fear-potentiated startle paradigm for assessing cognition in genetically altered mice.

Animals↗

A chromosomally encoded type III secretion pathway in Yersinia enterocolitica is important in virulence.

Numerous Gram-negative bacteria use a type III, or contact dependent, secretion system to deliver proteins into the cytosol of host cells. All of these systems identified to date have been shown to have a role in pathogenesis. We have identified 13 genes on the Yersinia enterocolitica chromosome that encode a type III secretion apparatus plus two associated putative regulatory genes. In order to determine the function of this chromosomally-encoded secretion apparatus, we created an in frame deletion of a gene that has homology to the hypothesized inner membrane pore, ysaV. The ysaV mutant strain failed to secrete eight proteins, called Ysps, normally secreted by the parental strain when grown at 28 degrees C in Luria-Bertani (LB) broth supplemented with 0.4 M NaCl. Disruption of the ysaV gene had no effect on motility or phospholipase activity, suggesting this chromosomally encoded type III secretion pathway is distinct from the flagella secretion pathway of Y. enterocolitica. Deletion of the ysaV gene in a virulence plasmid positive strain had no effect on in vitro secretion of Yops by the plasmid-encoded type III secretion apparatus. Secretion of the Ysps was unaffected by the presence or absence of the virulence plasmid, suggesting the chromosomally encoded and plasmid-encoded type III secretion pathways act independently. Y. enterocolitica thus has three type III secretion pathways that appear to act independently. The ysaV mutant strain was somewhat attenuated in virulence compared with the wild type in the mouse oral model of infection (an approximately 0.9 log difference in LD50). The ysaV mutant strain was nearly as virulent as the wild type when inoculated intraperitoneally in the mouse model. A ysaV probe hybridized to sequences in other Yersinia spp. and homologues were found in the incomplete Y. pestis genome sequence, indicating a possible role for this system throughout the genus.

Animals↗

Working memory of auditory localization.

To investigate brain mechanisms of sound location memory, we studied the distribution of brain activation with functional magnetic resonance imaging (fMRI) in subjects performing an audiospatial n-back task with three memory load levels. Working memory processing of audiospatial information activated areas in the superior, middle and inferior frontal gyri, and in the posterior parietal and middle temporal cortices. In a control experiment, fMRI during audio- and visuospatial 2-back task performances revealed only few differentially activated subregions between the two tasks. These results demonstrate that working memory processing of auditory locations involves a distributed network of brain areas and suggest that mnemonic processing of audio- and visuospatial information is directed along a common neural pathway in the posterior parietal and prefrontal cortices.

Acoustic Stimulation↗

D-xylose kinetics and hydrogen breath tests in functionally anephric patients using the 15-gram dose.

Malabsorptive evaluation in renal failure is difficult because most absorptive testing requires urinary collections. Kinetic analysis of d-xylose absorption and d-xylose breath testing were performed in an effort to establish an effective absorption test in functionally anephric patients. We studied 13 fasting renal failure patients with no diarrhea or symptoms suggesting malabsorption on two separate nondialysis days after they received 15 g oral d-xylose on day 1 and 10 g IV on day 2. Serum collections were used to calculate the kinetic rate constants and extent of d-xylose absorption. After the oral d-xylose, end expiratory breaths were collected every 15 minutes for 3 hours and were analyzed for H2 with gas chromatography. Five subjects also allowed upper endoscopy and duodenal biopsy. The mean absorption rate constant (Ka) and bioavailability (F) were similar to published values for normal subjects using the 15-g dose (0.936 min(-1); range, 0.227-1.96; and 74%, range 46-99, respectively). Of the patients, 12 had normal 1-hour serum d-xylose concentrations (>20 mg/dL). There was no clear inverse correlation between the rate constant for absorption or bioavailability and peak breath hydrogen or the area under the curve for breath H2 versus time. Using 15 g oral d-xylose, mean bioavailability and absorption rate constants are normal in functionally anephric patients with no clinical evidence of malabsorption. Three patients had elevated breath peak H2 concentrations, but there was no clear inverse correlation between bioavailability and the breath H2 values. A 1-hour serum dxylose concentration >20 mg/dL may be considered normal in this patient group, similar to patients with normal renal function.

Adult↗

Bulk modulus and high-pressure crystal structures of tetrakis(trimethylsilyl)methane C

The pressure dependence of the crystal structure of cubic tetrakis(trimethylsilyl)methane C[Si(CH3)3]4 (TC) (P < 16.0 GPa, T = 298 K) is reported using high-resolution angle-dispersive X-ray powder diffraction. The compound has crystal structures with the molecules in a cubic-close-packed (c.c.p.) arrangement. It shows three phase transitions in the measured pressure range. At ambient conditions, TC has space group Fm3m (Z = 4) with a = 12.8902 (2) A, V = 2141.8 (1) A3 (phase I). Between 0 and 0.13 GPa TC exhibits a first-order phase transition into a structure with space group Pa3 (phase II). A second first-order phase transition occurs between 0.2 and 0.28 GPa into a structure with space group P2(1)3 (phase III). Under non-hydrostatic pressure conditions (P > 10 GPa) a transformation is observed into a c.c.p. structure that is different from the face-centred-cubic structure at ambient conditions. A non-linear compression behaviour is observed, which could be described by a Vinet relation in the range 0.28-4.8 GPa. The extrapolated bulk modulus of the high-pressure phase III was determined to be K0 = 7.1 (8) GPa. The crystal structures in phase III are refined against X-ray powder data measured at several pressures between 0.49 and 4.8 GPa, and the molecules are found to be fully ordered. This is interpreted to result from steric interactions between neighbouring molecules, as shown by analysing the pressure dependence of intramolecular angles, torsion angles and intermolecular distances. Except for their cell dimensions, phases I, II and III are found to be isostructural to the corresponding phases at low temperatures.

Journal Article↗

High-pressure transformations of NbO2F

The ReO3-type structure NbO2F, niobium dioxyfluoride, has been studied at high pressures using diamond anvil cells and synchrotron X-ray radiation. High-pressure powder diffraction measurements have been performed up to 40.1 GPa. A phase transition from the cubic (Pm3m) ambient pressure structure to a rhombohedral (R3c) structure at 0.47 GPa has been observed. Rietveld refinements at 1.38, 1.96, 3.20, 6.23, 9.00 and 10.5 GPa showed that the transition involves an a-a-a- tilting of the cation-anion coordination octahedra and a change of the anion-anion arrangement to approach hexagonal close packing. Compression and distortion of the Nb(O/F)6 octahedra is also revealed by the Rietveld refinements. At 17-18 GPa, the diffraction pattern disappears and the structure becomes X-ray amorphous.

Journal Article↗