Evaluation of the Relationship Between Cognitive Impairment, Glycometabolism, and Nicotinic Acetylcholine Receptor Deficits in a Mouse Model of Alzheimer's Disease

PURPOSE: In patients with Alzheimer's disease (AD), the loss of cerebral nicotinic acetylcholine receptors (nAChRs) that are implicated in higher brain functions has been reported. However, it is unclear if nAChR deficits occur in association with cognitive impairments. The purpose of this study was to assess the relationship between nAChR deficits and cognitive impairments in a mouse model of AD (APP/PS2 mice). PROCEDURES: The cognitive abilities of APP/PS2 and wild-type mice (aged 2-16 months) were evaluated using the novel object recognition test. Double-tracer autoradiography analyses with 5-[125I]iodo-A-85380 ([125I]5IA: α4β2 nAChR imaging probe) and 2-deoxy-2-[18F]fluoro-D-glucose were performed in both mice of different ages. [123I]5IA-single-photon emission tomography (SPECT) imaging was also performed in both mice at 12 months of age. Furthermore, each age cohort was investigated for changes in cognitive ability and expression levels of α7 nAChRs and N-methyl-D-aspartate receptors (NMDARs). RESULTS: No significant difference was found between the APP/PS2 and wild-type mice at 2-6 months of age in terms of novel object recognition memory; subsequently, however, APP/PS2 mice showed a clear cognitive deficit at 12 months of age. [125I]5IA accumulation decreased in the brains of 12-month-old APP/PS2 mice, i.e., at the age at which cognitive impairments were first observed; this result was supported by a reduction in the protein levels of α4 nAChRs using Western blotting. nAChR deficits could be noninvasively detected by [123I]5IA-SPECT in vivo. In contrast, no significant changes in glycometabolism, expression levels of α7 nAChRs, or NMDARs were associated with cognitive impairments in APP/PS2 mice. CONCLUSION: A decrease in cerebral α4β2 nAChR density could act as a biomarker reflecting cognitive impairments associated with AD pathology

All-microwave manipulation of superconducting qubits with a fixed-frequency transmon coupler

All-microwave control of fixed-frequency superconducting quantum computing circuits is advantageous for minimizing the noise channels and wiring costs. Here we introduce a swap interaction between two data transmons assisted by the third-order nonlinearity of a coupler transmon under a microwave drive. We model the interaction analytically and numerically and use it to implement an all-microwave controlled-Z gate. The gate based on the coupler-assisted swap transition maintains high drive efficiency and small residual interaction over a wide range of detuning between the data transmons.Comment: 12 pages, 8 figure

What Do Self-Supervised Speech and Speaker Models Learn? New Findings From a Cross Model Layer-Wise Analysis

Self-supervised learning (SSL) has attracted increased attention for learning meaningful speech representations. Speech SSL models, such as WavLM, employ masked prediction training to encode general-purpose representations. In contrast, speaker SSL models, exemplified by DINO-based models, adopt utterance-level training objectives primarily for speaker representation. Understanding how these models represent information is essential for refining model efficiency and effectiveness. Unlike the various analyses of speech SSL, there has been limited investigation into what information speaker SSL captures and how its representation differs from speech SSL or other fully-supervised speaker models. This paper addresses these fundamental questions. We explore the capacity to capture various speech properties by applying SUPERB evaluation probing tasks to speech and speaker SSL models. We also examine which layers are predominantly utilized for each task to identify differences in how speech is represented. Furthermore, we conduct direct comparisons to measure the similarities between layers within and across models. Our analysis unveils that 1) the capacity to represent content information is somewhat unrelated to enhanced speaker representation, 2) specific layers of speech SSL models would be partly specialized in capturing linguistic information, and 3) speaker SSL models tend to disregard linguistic information but exhibit more sophisticated speaker representation.Comment: Accepted at ICASSP 202

RNA-seq-based evaluation of bicolor tepal pigmentation in Asiatic hybrid lilies (Lilium spp.)

Background: Color patterns in angiosperm flowers are produced by spatially and temporally restricted deposition of pigments. Identifying the mechanisms responsible for restricted pigment deposition is a topic of broad interest. Some dicots species develop bicolor petals, which are often caused by the post-transcriptional gene silencing (PTGS) of chalcone synthase (CHS) genes. An Asiatic hybrid lily (Lilium spp.) cultivar Lollypop develops bicolor tepals with pigmented tips and white bases. Here, we analyzed the global transcription of pigmented and non-pigmented tepal parts from Lollypop, to determine the main transcriptomic differences. Results: De novo assembly of RNA-seq data yielded 49,239 contigs (39,426 unigenes), which included a variety of novel transcripts, such as those involved in flavonoid-glycosylation and sequestration and in regulation of anthocyanin biosynthesis. Additionally, 1258 of the unigenes exhibited significantly differential expression between the tepal parts (false discovery rates 2-fold higher in the pigmented parts. Thus, LhMYB12 should be involved in the transcriptional regulation of the biosynthesis genes in bicolor tepals. Other factors that potentially suppress or enhance the expression of anthocyanin biosynthesis genes, including a WD40 gene, were identified, and their involvement in bicolor development is discussed. Conclusions: Our results indicate that the bicolor trait of Lollypop tepals is caused by the transcriptional regulation of anthocyanin biosynthesis genes and that the transcription profile of LhMYB12 provides a clue for elucidating the mechanisms of the trait. The tepal transcriptome constructed in this study will accelerate investigations of the genetic controls of anthocyanin color patterns, including the bicolor patterns, of Lilium spp

Photon-noise-tolerant dispersive readout of a superconducting qubit using a nonlinear Purcell filter

Residual noise photons in a readout resonator become a major source of dephasing for a superconducting qubit when the resonator is optimized for a fast, high-fidelity dispersive readout. Here, we propose and demonstrate a nonlinear Purcell filter that suppresses such an undesired dephasing process without sacrificing the readout performance. When a readout pulse is applied, the filter automatically reduces the effective linewidth of the readout resonator, increasing the sensitivity of the qubit to the input field. The noise tolerance of the device we fabricated is shown to be enhanced by a factor of three relative to a device with a linear filter. The measurement rate is enhanced by another factor of three by utilizing the bifurcation of the nonlinear filter. A readout fidelity of 99.4% and a QND fidelity of 99.2% are achieved using a 40-ns readout pulse. The nonlinear Purcell filter will be an effective tool for realizing a fast, high-fidelity readout without compromising the coherence time of the qubit.Comment: 13 pages, 9 figure

Spin fluctuations from Bogoliubov Fermi surfaces in the superconducting state of S-substituted FeSe

The study of the iron-based superconductor, FeSe, has resulted in various topics, such as the interplay among superconductivity, nematicity, and magnetism, Bardeen-Cooper-Schrieffer Bose-Einstein-condensation (BCS-BEC) crossover, and Fulde-Ferrell-Larkin-Ovchinnikov (FFLO) superconductivity. Recently, topologically protected nodal Fermi surfaces, referred to as Bogoliubov Fermi surfaces (BFSs), have garnered much attention. A theoretical model for the S-substituted FeSe system demonstrated that BFSs can manifest under the conditions of spin-orbit coupling, multi-band systems, and superconductivity with time-reversal symmetry breaking. Here we report the observation of spin fluctuations originating from BFSs in the superconducting (SC) state via $^{77}$Se-nuclear magnetic resonance measurements to 100 mK. In a heavily S-substituted FeSe, we found an anomalous enhancement of low-energy spin fluctuations deep in the SC state, which cannot be explained by an impurity effect. Such unusual behavior implies the presence of significant spin fluctuations of Bogoliubov quasiparticles, which are associated with possible nesting properties between BFSs

PHOSPHATEMIC INDEX EVALUATES PHOSPHORUS LOAD

Objective: Dietary phosphorus (P) restriction is crucial to treat hyperphosphatemia and reduce cardiovascular disease risk and mortality in patients with chronic kidney disease (CKD) and the wider population. Various methods for dietary P restriction exist, but the bioavailability of P in food should also be considered when making appropriate food choices to maintain patients’ quality of life. Here, we propose the ‘‘Phosphatemic Index’’ (PI) as a novel tool for evaluating dietary P load based on P bioavailability; we also evaluated the effect of continuous intake of different PI foods in mixed meals on serum intact fibroblast growth factor 23 concentration. Design and Methods: A 2-stage crossover study was conducted: Study 1: 20 healthy participants consumed 10 different foods containing 200 mg of P, and the PI was calculated from the area under the curve of a time versus serum P concentration curve; Study 2: 10 healthy participants consumed 4 different test meals (low, medium, or high PI meals or a control) over a 5-day period. Results: Study 1 showed milk and dairy products had high PI values, pork and ham had medium PI values, and soy and tofu had low PI values. In Study 2, ingestion of high PI test meals showed higher fasting serum intact fibroblast growth factor 23 levels and lower serum 1,25-dihydroxyvitamin D levels compared with ingestion of low PI test meals. Conclusion: These findings suggest that the PI can usefully evaluate the dietary P load of various foods and may help to make appropriate food choices for dietary P restriction in CKD patients