All signals, except sine waves, exhibit intrinsic modulations that affect perceptual masking. Reducing the physical intrinsic modulations of a broadband signal does not necessarily have a perceptual impact: auditory filtering can reintroduce modulations. Broadband signals with low intrinsic modulations after auditory filtering have proved difficult to design. To that end, this paper introduces a class of signals termed pulse-spreading harmonic complexes (PSHCs). PSHCs are generated by summing harmonically related components with such a phase that the resulting waveform exhibits pulses equally-spaced within a repetition period. The order of a PSHC determines its pulse rate. Simulations with a gamma-tone filterbank suggest an optimal pulse rate at which, after auditory filtering, the PSHC's intrinsic modulations are lowest. These intrinsic modulations appear to be less than those for broadband pseudo-random (PR) or low-noise (LN) noise. This hypothesis was tested in a modulation-detection experiment involving five modulation rates ranging from 8 to 128 Hz and both broadband and narrowband carriers using PSHCs, PR, and LN noise. PSHC showed the lowest thresholds of all broadband signals. Results imply that optimized PSHCs exhibit less intrinsic modulations after auditory filtering than any other broadband signal previously considered.
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Nat Chem Biol
January 2025
Fudan University Shanghai Cancer Center, Institutes of Biomedical Sciences, State Key Laboratory of Genetic Engineering, Shanghai Key Laboratory of Medical Epigenetics, Department of Oncology, Shanghai Medical College, Fudan University, Shanghai, China.
Chromatin and transcription regulators are critical to defining cell identity through shaping epigenetic and transcriptional landscapes, with their misregulation being closely linked to oncogenesis. Pharmacologically targeting these regulators, particularly the transcription-activating BET proteins, has emerged as a promising approach in cancer therapy, yet intrinsic or acquired resistance frequently occurs, with poorly understood mechanisms. Here, using genome-wide CRISPR screens, we find that BET inhibitor efficacy in mediating transcriptional silencing and growth inhibition depends on the auxiliary/arm/tail module of the Integrator-PP2A complex (INTAC), a global regulator of RNA polymerase II pause-release dynamics.
View Article and Find Full Text PDFBiomed Pharmacother
January 2025
Research Center of Integrated Traditional Chinese and Western Medicine, The Affiliated Traditional Chinese Medicine Hospital, Southwest Medical University, Luzhou 646000, China; Institute of Integrated Chinese and Western Medicine, Southwest Medical University, Luzhou 646000, China; Institute of Integrated Chinese and Western Medicine, Southwest Medical University, Luzhou 646000, China. Electronic address:
The interaction between renal intrinsic cells and macrophages plays a crucial role in the onset and progression of kidney diseases. In recent years, epigenetic mechanisms such as DNA methylation, histone modification, and non-coding RNA regulation have become essential windows for understanding these processes. This review focuses on how renal intrinsic cells (including tubular epithelial cells, podocytes, and endothelial cells), renal cancer cells, and mesenchymal stem cells influence the function and polarization status of macrophages through their own epigenetic alterations, and how the epigenetic regulation of macrophages themselves responds to kidney damage, thus participating in renal inflammation, fibrosis, and repair.
View Article and Find Full Text PDFJ Neural Eng
January 2025
University of Pittsburgh, 1622 Locust St, Pittsburgh, Pennsylvania, 15219, UNITED STATES.
Real-world implementation of brain-computer interfaces (BCI) for continuous control of devices should ideally rely on fully asynchronous decoding approaches. That is, the decoding algorithm should continuously update its output by estimating the user's intended actions from real-time neural activity, without the need for any temporal alignment to an external cue. This kind of open-ended temporal flexibility is necessary to achieve naturalistic and intuitive control, but presents a challenge: how do we know when it is appropriate to decode anything at all? Activity in motor cortex is dynamic and modulates with many different types of actions (proximal arm control, hand control, speech, etc.
View Article and Find Full Text PDFCereb Cortex
January 2025
School of AIDE, Center for Brain Science and Applications, IIT Jodhpur, NH-62, Surpura Bypass Rd, Karwar, Rajasthan 342030, India.
Optimal brain function is shaped by a combination of global information integration, facilitated by long-range connections, and local processing, which relies on short-range connections and underlying biological factors. With aging, anatomical connectivity undergoes significant deterioration, which affects the brain's overall function. Despite the structural loss, previous research has shown that normative patterns of functions remain intact across the lifespan, defined as the compensatory mechanism of the aging brain.
View Article and Find Full Text PDFJ Transl Med
January 2025
Department of Hematology, Ren Ji Hospital, Shanghai Jiao Tong University School of Medicine, Shanghai, 200127, China.
Background: Targeting exportin1 (XPO1) with Selinexor (SEL) is a promising therapeutic strategy for patients with multiple myeloma (MM). However, intrinsic and acquired drug resistance constitute great challenges. SEL has been reported to promote the degradation of XPO1 protein in tumor cells.
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