Timothy James Scholl

Dr. Timothy James Scholl

orcid

Research Focus & Metrics

Academic Career Length

41Years (1986-Present)

(Calculated once Scilit publication data is synced: current year − year of first publication + 1)

Representative Publications

View All Publications
1 January 2019 in eneuro
Verified
Journal Article
Open access
PDF file
RHRichard A. Harris
Richard A. Harris
ALAsad Lone
Asad Lone
HLHeeseung Lim
Heeseung Lim
FMFrancisco Martinez
Francisco Martinez
AFAriel K. Frame
Ariel K. Frame
RCRobert C. Cumming
Robert C. Cumming
The consolidation of newly formed memories and their retrieval are energetically demanding processes. Aerobic glycolysis (AG), also known as the Warburg effect, consists of the production of lactate from glucose in the presence of oxygen. The astrocyte neuron lactate shuttle hypothesis posits that astrocytes process glucose by AG to generate lactate, which is used as a fuel source within neurons to maintain synaptic activity. Studies in mice have demonstrated that lactate transport between astrocytes and neurons is required for long-term memory formation, yet the role of lactate production in memory acquisition and retrieval has not previously been explored. Here, we examined the effect of dichloroacetate (DCA), a chemical inhibitor of lactate production, on spatial learning and memory in mice using the Morris water maze (MWM).In vivohyperpolarized13C-pyruvate magnetic resonance spectroscopy revealed decreased conversion of pyruvate to lactate in the mouse brain following DCA administration, concomitant with a reduction in the phosphorylation of pyruvate dehydrogenase. DCA exposure before each training session in the MWM impaired learning, which subsequently resulted in impaired memory during the probe trial. In contrast, mice that underwent training without DCA exposure, but received a single DCA injection before the probe trial exhibited normal memory. Our findings indicate that AG plays a key role during memory acquisition but is less important for the retrieval of established memories. Thus, the activation of AG may be important for learning-dependent synaptic plasticity rather than the activation of signaling cascades required for memory retrieval.

29 October 2012 in Contrast Media & Molecular Imaging
Verified
Journal Article
Open access
PDF file
NCN. Chattergoon
N. Chattergoon
FMF. Martínez‐Santiesteban
F. Martínez‐Santiesteban
WHW. B. Handler
W. B. Handler
Jan Henrik Ardenkjaer-LarsenJan Henrik Ardenkjaer-Larsen
Jan Henrik Ardenkjaer-Larsen
TSTimothy James Scholl
Timothy James Scholl
In vivo metabolism of hyperpolarized pyruvate has been demonstrated to be an important probe of cellular glycolysis in diseases such as cancer. The usefulness of hyperpolarized 13C imaging is dependent on the relaxation rates of the 13C‐enriched substrates, which in turn depend on chemical conformation and properties of the dissolution media such as buffer composition, solution pH, temperature and magnetic field. We have measured the magnetic field dependence of the spin–lattice relaxation time of hyperpolarized [1‐13C]pyruvate using field‐cycled relaxometry. [1‐13C]pyruvate was hyperpolarized using dynamic nuclear polarization and then rapidly thawed and dissolved in a buffered solution to a concentration of 80 mmol l−1 and a pH of ~7.8. The hyperpolarized liquid was transferred within 8 s to a fast field‐cycling relaxometer with a probe tuned for detection of 13C at a field strength of ~0.75 T. The magnetic field of the relaxometer was rapidly varied between relaxation and acquisition fields where the sample magnetization was periodically measured using a small flip angle. Data were recorded for relaxation fields varying between 0.237 mT and 0.705 T to map the T1 dispersion of the C‐1 of pyruvate. Using similar methods, we also determined the relaxivity of the triarylmethyl radical (OX063; used for dynamic nuclear polarization) on the C‐1 of pyruvate at field strengths of 0.001, 0.01, 0.1 and 0.5 T using 0.075, 1.0 and 2.0 mmol l−1 concentrations of OX063 in the hyperpolarized pyruvate solution. Copyright © 2012 John Wiley & Sons, Ltd.

7 January 2014 in Journal of Medicinal Chemistry
Verified
Journal Article
Closed access
WCWeiran Cheng
Weiran Cheng
IHInga E. Haedicke
Inga E. Haedicke
JNJoris Nofiele
Joris Nofiele
FMFrancisco Martinez
Francisco Martinez
KBKiran Beera
Kiran Beera
XZXiao-an Zhang
Xiao-an Zhang

11 June 1999 in Monthly Notices of the Royal Astronomical Society
Verified
Journal Article
Open access
PDF file
RHR. A. Holt
R. A. Holt
TSTimothy James Scholl
Timothy James Scholl
SRS. D. Rosner
S. D. Rosner
Hyperfine structure can have a significant effect on the accuracy of astrophysical determinations of chemical abundances, and absolute wavenumbers ar

4 October 1993 in Physical Review Letters
Verified
Journal Article
Closed access
PDF file
TSTimothy James Scholl
Timothy James Scholl
RCR. Cameron
R. Cameron
SRS. D. Rosner
S. D. Rosner
LZL. Zhang
L. Zhang
RHR. A. Holt
R. A. Holt
JGJ. D. Gillaspy
J. D. Gillaspy
We have used fast-ion-beam laser spectroscopy to measure the 1s2s3s-1s2p3 Po intervals in Be iii to an absolute accuracy of 1 part in 108. Our results are (in cm−1): σ(1s2s3 S1-1s2p3 P0o=28 864.6120(4), σ(1s2s3 S1−1s2p3 P1o=26 853.0534(3), σ(1s2s3 S1−1s2p3 P2o) =26 867.9484(3). These results are an improvement over previous measurements by nearly 3 orders of magnitude and show evidence of uncalculated O(α4 Z4) relativistic corrections. Once those terms are computed, our measurement will allow QED calculations in two-electron atoms to be tested at the 100 ppm level.

7 December 2012 in Journal of Materials Chemistry B
Verified
Journal Article
Closed access
PDF file
ASAbdolrasoul Soleimani
Abdolrasoul Soleimani
FMFrancisco Martínez
Francisco Martínez
VEVasiliki Economopoulos
Vasiliki Economopoulos
PFPaula Foster
Paula Foster
TSTimothy James Scholl
Timothy James Scholl
Elizabeth GilliesElizabeth Gillies
Elizabeth Gillies
Polymer cross-linking was explored as an approach for increasing the relaxivity of macromolecular contrast agents for magnetic resonance imaging. Poly(ethylene glycol) methyl ether methacrylate, N-(2-aminoethyl)methacrylamide hydrochloride, and the cross-linker ethylene glycol dimethacrylate were copolymerized under free radical conditions. By tuning the cross-linker content and reaction concentration, it was possible to obtain 10 nm nanogels in a single synthetic step. The pendant amine moieties were functionalized with an isothiocyanate derivative of diethylenetriaminepentaacetic acid (DTPA) and Gd(III) was chelated. In comparison with a linear control polymer prepared under the same conditions in the absence of the cross-linking agent, the nanogel contrast agent did exhibit enhanced relaxivity with an r1 of 20.8 ± 0.2 at 20 MHz and 17.5 ± 0.4 at 60 MHz (corresponding to the clinical field strength of 1.5 T). The nuclear magnetic resonance dispersion profile was modeled to demonstrate that the enhanced relaxivity was a result of the nanogel agent's increased rotational correlation time, that is proposed to result from the constraint on motion imparted by the cross-linking. T1 weighted imaging in mice showed enhanced contrast and vascular circulation for the nanogel relative to Gd(III)–DTPA (Magnevist) demonstrating the future promise of these new agents.