A neuropeptide code for itch Chen, Zhou-Feng
Nature reviews. Neuroscience,
12/2021, Letnik:
22, Številka:
12
Journal Article
Recenzirano
Odprti dostop
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.
Stable isotope composition of speleothems reflects the physicochemical condition of their formation environment such as the local temperature and the isotopic composition of surface precipitation, ...making them one of the best archives of terrestrial climate. However, quantitative reconstruction of paleo-temperature from speleothem isotope records is challenging, because most speleothems do not form in isotope equilibrium with the drip water. These disequilibrium isotope effects, often thought to arise from the rapid degassing of CO2 from a thin water film, vary among different speleothems and over time, and hinder the applications of many isotope thermometers in speleothems, including both the conventional carbonate-water oxygen isotope thermometer and the recently developed carbonate clumped isotope thermometer. Here we present an isotope-enabled reaction-diffusion model of speleothem formation (IsoCave), and use it to systematically examine the patterns and controls of the disequilibrium isotope effects in speleothems (δ13C, δ18O, Δ′17O, Δ47, Δ48 and Δ49) and explore their implications for isotope thermometry in speleothems.
We show that prior calcite precipitation, cave air pCO2 and δ13CCO2exert the strongest controls on the disequilibrium isotope effects in speleothems, followed by cave temperature, water film thickness and water drip rate. Together, changes in these environment parameters explain the variations of disequilibrium isotope effects in natural speleothems. Our model reproduces the apparent temperature dependence of oxygen isotope compositions of speleothems compiled from multiple caves over a large temperature range, but highlights the challenges in the application of speoleothem-specific calibration of isotope thermometers due to the effects of non-temperature factors. Further, we show the disequilibrium effects in different isotope systems are highly correlated. The slopes of these correlations reflect mainly the kinetic isotope fractionations associated with HCO3− dehydration and dehydroxylation reactions, and remain relatively constant despite changes in environmental conditions especially for speleothems formed during the early evolution period of drip water. Based on these correlations, specifically the correlation between disequilibrium Δ47 and Δ48 effects, we propose a novel approach to quantitatively correct for disequilibrium isotope effects in speleothems and derive more accurate estimates of speleothem formation temperatures. Application of this coupled Δ47-Δ48 approach to synthetic speleothem isotope records reproduces the speleothem formation temperatures, suggesting new opportunities for quantitative paleo-temperature reconstruction based on speleothem isotope records.
Abstract
In the process of aircraft design, it is necessary to study the flight ground transit scenario. In this paper, to research a typical flight ground transit scenario, a domestic airport is ...selected, and the typical values of taxi distance, service transit time, and arrival flight time are assessed, analyzed, and given after the influence of passenger flow, runway, terrain, and temperature. This typical transit scenario can be used for the relevant calculations of flight transit capacity in the top-level design of the aircraft.
In this paper, the n-dimensional discretized model of the two-link flexible manipulator is developed by the assumed mode method (AMM). Subsequently, based on the discretized dynamic model, both ...full-state feedback control and output feedback control are investigated to achieve the trajectory tracking and vibration suppression. In order to guarantee the stability strictly, uniform ultimate boundedness (UUB) of the closed-loop system is realized by the Lyapunov's stability. Furthermore, through appropriately choosing control parameters, the states of the system will converge to zero within a small neighborhood. Eventually, extensive simulations and experiments on the Quanser platform for a two-link robotic manipulator are carried out to demonstrate the feasibility of the proposed neural network controller.
Abstract
Motivation
Anti-cancer peptides (ACPs) have recently emerged as promising therapeutic agents for cancer treatment. Due to the avalanche of protein sequence data in the post-genomic era, ...there is an urgent need to develop automated computational methods to enable fast and accurate identification of novel ACPs within the vast number of candidate proteins and peptides.
Results
To address this, we propose a novel predictor named Anti-Cancer peptide Predictor with Feature representation Learning (ACPred-FL) for accurate prediction of ACPs based on sequence information. More specifically, we develop an effective feature representation learning model, with which we can extract and learn a set of informative features from a pool of support vector machine-based models trained using sequence-based feature descriptors. By doing so, the class label information of data samples is fully utilized. To improve the feature representation, we further employ a two-step feature selection technique, resulting in a most informative five-dimensional feature vector for the final peptide representation. Experimental results show that such five features provide the most discriminative power for identifying ACPs than currently available feature descriptors, highlighting the effectiveness of the proposed feature representation learning approach. The developed ACPred-FL method significantly outperforms state-of-the-art methods.
Availability and implementation
The web-server of ACPred-FL is available at http://server.malab.cn/ACPred-FL.
Supplementary information
Supplementary data are available at Bioinformatics online.
Long non-coding RNAs (lncRNAs) have been confirmed as crucial regulators in tumorgenesis. Small nucleolar RNA host gene 16 (SNHG16) has been recently uncovered to be a potential oncogene in several ...types of cancers. However, its expression level and potential role in cervical cancer remain uncertain. In our research, we assessed the expression level of SNHG16 in clinical cervical cancer tissues and cells. We made use of functional assays to determine the biological effects of SNHG16 on cell proliferation and migration of cervical cancer. By employing the bioinformatics analysis tools, we revealed that miR-216-5p could interact with SNHG16 and there existed a negative correlation between the expression levels of miR-216-5p and SNHG16 in cervical cancer specimens. Furthermore, RIP assay, RNA pulldown system and dual luciferase reporter assays confirmed that SNHG16 directly targeted miR-216-5p by harboring the binding sites of microRNA in the SNHG16 sequence. Additionally, bioinformatics analysis provided an evidence that ZEB1 was a potential target of miR-216-5p. Collectively, it was suggested that SNHG16 could serve as an oncogene that promoted tumor progression by acting as an endogenous ‘sponge’ to regulate miR-216A-5p/ZEB1.
Rock fractures are ubiquitous in geological systems and usually provide dominant pathways for fluid flow in fractured reservoirs. When the flowing fluid is reactive, fracture dissolution expands the ...aperture and forms various dissolution patterns that amplify the pathways. Previous works focused on the dissolution processes in Hele‐Shaw cells (parallel‐plate) and porous media, but the transitions of dissolution patterns in radial rough fractures are not well understood. Here we combine flow‐visualization experiments with theoretical analysis to elucidate the transitions of dissolution patterns under various flow‐rate and reaction‐rate conditions. We observe and quantify three distinct dissolution morphologies as compact, wormhole, and uniform patterns. We show that the critical Péclet numbers, corresponding to the transitions from compact to wormhole and to uniform patterns, increase with the reaction rate. Based on the growth of dissolution channels in the flow and transverse directions, we establish a theoretical model that describes the transitions of these three distinct dissolution patterns. The phase diagram predicted by the model exhibits good agreement with our experimental results and also well captures the pattern transitions reported in the previous studies. This work improves the understanding on how fracture aperture expands in the dissolution processes that lead to various dissolution channels. Our work is also critical for controlling the fluid flow behavior in dissolving natural rock fractures in subsurface flow systems.
Key Points
We visualize and quantify three distinct dissolution patterns in radial rough fractures
We propose a theoretical model to predict the transitions of dissolution patterns affected by the flow rate and the dissolution kinetic
A phase diagram predicted by the model shows good agreement with our experiments and with the existing experiments and simulations
In this paper we give a new, and shorter, proof of Huber’s theorem Theorem 13 in Huber (Comment Math Helve 32:13–72, 1958) which affirms that for a connected open Riemann surface endowed with a ...complete conformal Riemannian metric, if the negative part of its Gaussian curvature has finite mass, then the Riemann surface is homeomorphic to the interior of a compact surface with boundary, and thus it has finite topological type. We will also show that such Riemann surface is parabolic Theorem 15 in Huber (Comment Math Helve 32:13–72, 1958).
For a holomorphic one-form
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on a weakly 1-complete manifold
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with certain properties, we will discuss the connectivity of the pair
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The osteogenic differentiation of mesenchymal stem cells (MSCs) is governed by multiple mechanisms. Growing evidence indicates that ubiquitin‐dependent protein degradation is critical for the ...differentiation of MSCs and bone formation; however, the function of ubiquitin‐specific proteases, the largest subfamily of deubiquitylases, remains unclear. Here, we identify USP34 as a previously unknown regulator of osteogenesis. The expression of USP34 in human MSCs increases after osteogenic induction while depletion of USP34 inhibits osteogenic differentiation. Conditional knockout of Usp34 from MSCs or pre‐osteoblasts leads to low bone mass in mice. Deletion of Usp34 also blunts BMP2‐induced responses and impairs bone regeneration. Mechanically, we demonstrate that USP34 stabilizes both Smad1 and RUNX2 and that depletion of Smurf1 restores the osteogenic potential of Usp34‐deficient MSCs in vitro. Taken together, our data indicate that USP34 is required for osteogenic differentiation and bone formation.
Synopsis
Combining in vitro and in vivo approaches, this study identifies ubiquitin‐specific protease USP34 as a new regulator of osteogenesis. USP34 activates BMP2 signaling by deubiquitinating and stabilizing Smad1 and RUNX2, thereby promoting osteogenic differentiation.
Depletion of USP34 impairs osteogenic differentiation in vivo and in vitro.
Usp34‐depleted mice have low bone mass.
USP34 is required to activate BMP2 signaling during bone formation.
USP34 stabilizes Smad1 and RUNX2 by deubiquitination.
USP34 counteracts ubiquitin ligase Smurf1, which targets Smad1 and RUNX2.
Combining in vitro and in vivo approaches, this study identifies USP34 as a new regulator of osteogenesis via targeted stabilization of Smad1 and RUNX2, illustrating a role for protein deubiquitination in bone formation.
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