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A neuropeptide code for itch
Itch is one of the most primal sensations, being both ubiquitous and important for the well-being of animals. For more than a century, a desire to understand how itch is encoded by the nervous system has prompted the advancement of many theories. Within the past 15 years, our understanding of the molecular and neural mechanisms of itch has undergone a major transformation, and this remarkable progress continues today without any sign of abating. Here I describe accumulating evidence that indicates that itch is distinguished from pain through the actions of itch-specific neuropeptides that relay itch information to the spinal cord. According to this model, classical neurotransmitters transmit, inhibit and modulate itch information in a context-, space- and time-dependent manner but do not encode itch specificity. Gastrin-releasing peptide (GRP) is proposed to be a key itch-specific neuropeptide, with spinal neurons expressing GRP receptor (GRPR) functioning as a key part of a convergent circuit for the conveyance of peripheral itch information to the brain.The encoding of itch by peripheral and central neural circuits is a topic of long-standing interest in the somatosensory field. Here, Zhou-Feng Chen outlines a model for itch coding that emphasizes the role of neuropeptides in conveying itch information from the periphery to the spinal cord.
Journal Article
Polygenic prediction via Bayesian regression and continuous shrinkage priors
Polygenic risk scores (PRS) have shown promise in predicting human complex traits and diseases. Here, we present PRS-CS, a polygenic prediction method that infers posterior effect sizes of single nucleotide polymorphisms (SNPs) using genome-wide association summary statistics and an external linkage disequilibrium (LD) reference panel. PRS-CS utilizes a high-dimensional Bayesian regression framework, and is distinct from previous work by placing a continuous shrinkage (CS) prior on SNP effect sizes, which is robust to varying genetic architectures, provides substantial computational advantages, and enables multivariate modeling of local LD patterns. Simulation studies using data from the UK Biobank show that PRS-CS outperforms existing methods across a wide range of genetic architectures, especially when the training sample size is large. We apply PRS-CS to predict six common complex diseases and six quantitative traits in the Partners HealthCare Biobank, and further demonstrate the improvement of PRS-CS in prediction accuracy over alternative methods.
Polygenic risk scores (PRS) have the potential to predict complex diseases and traits from genetic data. Here, Ge et al. develop PRS-CS which uses a Bayesian regression framework, continuous shrinkage (CS) priors and an external LD reference panel for polygenic prediction of binary and quantitative traits from GWAS summary statistics.
Journal Article
Poets of the Chinese revolution : Chen Duxiu, Zheng Chaolin, Chen Yi, Mao Zedong
\"How poetry and revolution meshed in Red China. This is a book of poems by four veteran Chinese revolutionaries. Chen Duxiu led China's early cultural awakening before founding the Communist Party in 1921. Mao led the Party to power in 1949. Zheng Chaolin, Chen Duxiu's disciple and, like him, a convert to Trotskyism, spent 34 years in jail, first under the Nationalists and then under Mao. The guerrilla Chen Yi wrote poems in mountain bivouacs or the heat of battle. All wrote in the classical style, which Mao Zedong officially proscribed, though he and other leaders kept using it. Poetry, especially classical poetry, plays a different role in China, and in Chinese revolution, from in the West - it is collective and collaborative. The four poets were entangled with one another in various ways. Chen Duxiu inspired Mao, though Mao later denounced him. Mao and Zheng joined the leadership under Chen Duxiu in the 1920s, though Mao later gaoled Zheng. The maverick Chen Yi was Zheng's associate in France and Mao's comrade-in-arms in China, but he clashed with the Maoists in the Cultural Revolution. Together, the four poets illustrate the complex relationship between Communist revolution and Chinese cultural tradition\"-- Provided by publisher.
BOOK
m6A modification: recent advances, anticancer targeted drug discovery and beyond
Abnormal N6-methyladenosine (m6A) modification is closely associated with the occurrence, development, progression and prognosis of cancer, and aberrant m6A regulators have been identified as novel anticancer drug targets. Both traditional medicine-related approaches and modern drug discovery platforms have been used in an attempt to develop m6A-targeted drugs. Here, we provide an update of the latest findings on m6A modification and the critical roles of m6A modification in cancer progression, and we summarize rational sources for the discovery of m6A-targeted anticancer agents from traditional medicines and computer-based chemosynthetic compounds. This review highlights the potential agents targeting m6A modification for cancer treatment and proposes the advantage of artificial intelligence (AI) in the discovery of m6A-targeting anticancer drugs.
Graphical abstract
Three stages of m6A-targeting anticancer drug discovery: traditional medicine-based natural products, modern chemical modification or synthesis, and artificial intelligence (AI)-assisted approaches for the future.
Journal Article
Extended topological valley-locked surface acoustic waves
Stable and efficient guided waves are essential for information transmission and processing. Recently, topological valley-contrasting materials in condensed matter systems have been revealed as promising infrastructures for guiding classical waves, for they can provide broadband, non-dispersive and reflection-free electromagnetic/mechanical wave transport with a high degree of freedom. In this work, by designing and manufacturing miniaturized phononic crystals on a semi-infinite substrate, we experimentally realized a valley-locked edge transport for surface acoustic waves (SAWs). Critically, original one-dimensional edge transports could be extended to quasi-two-dimensional ones by doping SAW Dirac “semimetal” layers at the boundaries. We demonstrate that SAWs in the extended topological valley-locked edges are robust against bending and wavelength-scaled defects. Also, this mechanism is configurable and robust depending on the doping, offering various on-chip acoustic manipulation,
e.g
., SAW routing, focusing, splitting, and converging, all flexible and high-flow. This work may promote future hybrid phononic circuits for acoustic information processing, sensing, and manipulation.
Here the authors provide experimental evidence of extended topological valley-locked states. By splicing together Dirac semimetals and topological insulators, they demonstrate reduced backscattering and enhanced matching of SAW with interdigital transducers proposing this system for topological acoustics devices.
Journal Article
Observation of higher-order non-Hermitian skin effect
Beyond the scope of Hermitian physics, non-Hermiticity fundamentally changes the topological band theory, leading to interesting phenomena, e.g., non-Hermitian skin effect, as confirmed in one-dimensional systems. However, in higher dimensions, these effects remain elusive. Here, we demonstrate the spin-polarized, higher-order non-Hermitian skin effect in two-dimensional acoustic higher-order topological insulators. We find that non-Hermiticity drives wave localizations toward opposite edges upon different spin polarizations. More interestingly, for finite systems with both edges and corners, the higher-order non-Hermitian skin effect leads to wave localizations toward two opposite corners for all the bulk, edge and corner states in a spin-dependent manner. We further show that such a skin effect enables rich wave manipulation by configuring the non-Hermiticity. Our study reveals the intriguing interplay between higher-order topology and non-Hermiticity, which is further enriched by the pseudospin degree of freedom, unveiling a horizon in the study of non-Hermitian physics.
Though non-Hermitian physics has contributed toward the advance of research in quantum, electronic and classical systems, previous work focused on zero- or one-dimensional systems. Here, the authors report higher-order non-Hermitian skin effects in a 2D acoustic higher-order topological insulator.
Journal Article
A review on non-Hermitian skin effect
The past decades have witnessed the flourishing of non-Hermitian physics in non-conservative systems, leading to unprecedented phenomena of unidirectional invisibility, enhanced sensitivity and more recently the novel topological features such as bulk Fermi arcs. Among them, growing efforts have been invested to an intriguing phenomenon, known as the non-Hermitian skin effect (NHSE). Here, we review the recent progress in this emerging field. By starting from the one-dimensional (1D) case, the fundamental concepts of NHSE, its minimal model, the physical meanings and consequences are elaborated in details. In particular, we discuss the NHSE enriched by lattice symmetries, which gives rise to unique non-Hermitian topological properties with revised bulk-boundary correspondence (BBC) and new definitions of topological invariants. Then we extend the discussions to two and higher dimensions, where dimensional surprises enable even more versatile NH.SE phenomena. Extensions of NHSE assisted with extra degrees of freedom such as long-range coupling, pseudospins, magnetism, non-linearity and crystal defects are also reviewed. This is followed by the contemporary experimental progress for NHSE. Finally, we provide the outlooks to possible future directions and developments.
Journal Article