Notes

Continuing development of shoulder ache together with job-related repetitive weight: components of tendon pathology along with anxiety.
Crown-like structures (CLSs) are adipose microenvironments of macrophages engulfing adipocytes. Their histological density in visceral adipose tissue (VAT) predicts metabolic disorder progression in obesity and is believed to initiate obesity comorbidities. Here, we use three-dimensional (3D) light sheet microscopy and deep learning to quantify 3D features of VAT CLSs in lean and obese states. Obese CLS densities are significantly higher, composing 3.9% of tissue volume compared with 0.46% in lean tissue. Across the states, individual CLS structural characteristics span similar ranges; however, subpopulations are distinguishable. Obese VAT contains large CLSs absent from lean tissues, located near the tissue center, while lean CLSs have higher volumetric cell densities and prolate shapes. These features are consistent with inefficient adipocyte elimination in obesity that contributes to chronic inflammation, representing histological biomarkers to assess adipose pathogenesis. This tissue processing, imaging, and analysis pipeline can be applied to quantitatively classify 3D microenvironments across diverse tissues.Living tissues embody a unique class of hybrid materials in which active and thermal forces are inextricably linked. Mechanical characterization of tissues demands descriptors that respect this hybrid nature. In this work, we develop a microrheology-based force spectrum analysis (FSA) technique to dissect the active and passive fluctuations of the extracellular matrix (ECM) in three-dimensional (3D) cell culture models. In two different stromal models and a 3D breast cancer spheroid model, our FSA reveals emergent hybrid dynamics that involve both high-frequency stress stiffening and low-frequency fluidization of the ECM. We show that this is a general consequence of nonlinear coupling between active forces and the frequency-dependent viscoelasticity of stress-stiffening networks. In 3D breast cancer spheroids, this dual active stiffening and fluidization is tightly connected with invasion. Our results suggest a mechanism whereby breast cancer cells reconcile the seemingly contradictory requirements for both tension and malleability in the ECM during invasion.Wnt/β-catenin signaling requires inhibition of a multiprotein destruction complex that targets β-catenin for proteasomal degradation. SOX9 is a potent antagonist of the Wnt pathway and has been proposed to act through direct binding to β-catenin or the β-catenin destruction complex. Here, we demonstrate that SOX9 promotes turnover of β-catenin in mammalian cell culture, but this occurs independently of the destruction complex and the proteasome. This activity requires SOX9's ability to activate transcription. Transcriptome analysis revealed that SOX9 induces the expression of the Notch coactivator Mastermind-like transcriptional activator 2 (MAML2), which is required for SOX9-dependent Wnt/β-catenin antagonism. MAML2 promotes β-catenin turnover independently of Notch signaling, and MAML2 appears to associate directly with β-catenin in an in vitro binding assay. This work defines a previously unidentified pathway that promotes β-catenin degradation, acting in parallel to established mechanisms. SOX9 uses this pathway to restrict Wnt/β-catenin signaling.The invention of the maser stimulated revolutionary technologies such as lasers and atomic clocks. Yet, realizations of masers are still limited; in particular, the physics of masers remains unexplored in periodically driven (Floquet) systems, which are generally defined by time-periodic Hamiltonians and enable observation of many exotic phenomena such as time crystals. Here, we investigate the Floquet system of periodically driven 129Xe gas under damping feedback and unexpectedly observe a multimode maser that oscillates at frequencies of transitions between Floquet states. Our findings extend maser techniques to Floquet systems and open avenues to probe Floquet phenomena unaffected by decoherence, enabling a previously unexplored class of maser sensors. As a first application, our maser offers the capability of measuring low-frequency (1 to 100 mHz) magnetic fields with subpicotesla-level sensitivity, which is substantially better than state-of-the-art magnetometers and can be applied to, for example, ultralight dark matter searches.Mass production of zigzag and near-zigzag single-wall carbon nanotubes (SWCNTs), whether by growth or separation, remains a challenge, which hinders the disclosure of their previously unknown property and practical applications. Here, we report a method to separate SWCNTs by chiral angle through temperature control of a binary surfactant system of sodium cholate (SC) and SDS in gel chromatography. Eleven types of single-chirality SWCNT species with chiral angle less than 20° were efficiently separated including multiple zigzag and near-zigzag species. Among them, (7, 3), (8, 3), (8, 4), (9, 1), (9, 2), (10, 2), and (11, 1), were produced on the submilligram scale. The spectral detection results indicate that lowering the temperature induced selective adsorption and reorganization of the SC/SDS cosurfactants on SWCNTs with different chiral angles, amplifying their interaction difference with gel. Clofarabine clinical trial We believe that this work is an important step toward industrial separation of single-chirality zigzag and near-zigzag SWCNTs.Translation is a crucial process in cancer development and progression. Many oncogenic signaling pathways target the translation initiation stage to satisfy the increased anabolic demands of cancer cells. Using quantitative profiling of initiating ribosomes, we found that ribosomal pausing at the start codon serves as a "brake" to restrain the translational output. In response to oncogenic RAS signaling, the initiation pausing relaxes and contributes to the increased translational flux. Intriguingly, messenger RNA (mRNA) m6A modification in the vicinity of start codons influences the behavior of initiating ribosomes. Under oncogenic RAS signaling, the reduced mRNA methylation leads to relaxed initiation pausing, thereby promoting malignant transformation and tumor growth. Restored initiation pausing by inhibiting m6A demethylases suppresses RAS-mediated oncogenic translation and subsequent tumorigenesis. Our findings unveil a paradigm of translational control that is co-opted by RAS mutant cancer cells to drive malignant phenotypes.
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