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Caplan, M.

Publications and source records attributed to Caplan, M..

2 recordsLinked to original sources

Reverse Correlation Uncovers More Complete Tinnitus Spectra

GoalThis study validates an approach to characterizing the sounds experienced by tinnitus patients via reverse correlation, with potential for characterizing a wider range of sounds than currently possible. MethodsTen normal-hearing subjects assessed the subjective similarity of random auditory stimuli and target tinnitus-like sounds ("buzzing" and "roaring"). Reconstructions of the targets were obtained by regressing subject responses on the stimuli, and were compared for accuracy to the frequency spectra of the targets using Pearsons r. ResultsReconstruction accuracy was significantly higher than chance across subjects: buzzing (M = 0.53, SD = 0.27): t(9) = 5.766, p < 0.001; roaring (M = 0.57, SD = 0.30): t(9) = 5.76, p < 0.001. ConclusionReverse correlation can accurately reconstruct nontonal tinnitus-like sounds in normal-hearing subjects, indicating its potential for characterizing the sounds experienced by patients with non-tonal tinnitus. Impact StatementCharacterization of tinnitus sounds can inform treatment by facilitating individualized sound therapies, leading to better outcomes for patients suffering from the cognitive and psychological effects of tinnitus.

bioengineering↗

Loss of FBXO9 enhances proteasome activity and promotes aggressiveness in acute myeloid leukemia

The hematopoietic system is maintained throughout life by hematopoietic stem cells that are capable of differentiating into all hematopoietic lineages. An intimate balance between self-renewal, differentiation, and quiescence is required to maintain hematopoiesis. Disruption of this balance can result in hematopoietic malignancy, including acute myeloid leukemia (AML). FBXO9, from the F-box E3 ubiquitin ligases, is down-regulated in patients with AML compared to normal bone marrow. FBXO9 is the substrate recognition component of the Skp1-Cullin-F-box (SCF)-type E3 ligase complex. FBXO9 is highly expressed in hematopoietic stem and progenitor populations, which contain the tumor-initiating population in AML. In AML patients, decrease in FBXO9 expression is most pronounced in patients with the inversion of chromosome 16 (inv(16)), a rearrangement that generates the transcription factor fusion gene, CBFB-MYH11. To study FBXO9 in malignant hematopoiesis, we generated a conditional knockout mouse model using a novel CRISPR/Cas9 strategy. Our data show that deletion of Fbxo9 in mice expressing Cbfb-MYH11 leads to markedly accelerated and aggressive leukemia development. In addition, we find loss of FBXO9 leads to increased proteasome expression and tumors are more sensitive to bortezomib suggesting that FBXO9 expression may predict patient response to bortezomib treatment.

cancer biology↗