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To convert intentions into actions, movement instructions must pass from the brain to downstream motor circuits through descending neurons (DNs). These include small sets of command-like neurons that are sufficient to drive behaviours1-the circuit mechanisms for which remain unclear. Here we show that command-like DNs in Drosophila directly recruit networks of additional DNs to orchestrate behaviours that require the active control of numerous body parts. Specifically, we found that command-like DNs previously thought to drive behaviours alone2-4 in fact co-activate larger populations of DNs. Connectome analyses and experimental manipulations revealed that this functional recruitment can be explained by direct excitatory connections between command-like DNs and networks of interconnected DNs in the brain. Descending population recruitment is necessary for behavioural control: DNs with many downstream descending partners require network co-activation to drive complete behaviours and drive only simple stereotyped movements in their absence. These DN networks reside within behaviour-specific clusters that inhibit one another. These results support a mechanism for command-like descending control in which behaviours are generated through the recruitment of increasingly large DN networks that compose behaviours by combining multiple motor subroutines.
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Encéfalo , Conectoma , Drosophila melanogaster , Neurônios Motores , Rede Nervosa , Animais , Feminino , Comportamento Animal/fisiologia , Encéfalo/citologia , Encéfalo/fisiologia , Drosophila melanogaster/citologia , Drosophila melanogaster/fisiologia , Neurônios Motores/fisiologia , Movimento/fisiologia , Rede Nervosa/fisiologiaRESUMO
We describe early and recent advances in the fascinating field of combined magnetic and optical properties of inorganic coordination compounds and in particular of 3d-4f single molecule magnets. We cover various applied techniques which allow for the correlation of results obtained in the frequency and time domain in order to highlight the specific properties of these compounds and the future challenges towards multidimensional spectroscopic tools. An important point is to understand the details of the interplay of magnetic and optical properties through performing time-resolved studies in the presence of external fields especially magnetic ones. This will enable further exploration of this fundamental interactions i. e. the two components of electromagnetic radiation influencing optical properties.
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The 20-nuclearity compound [Fe8Dy12(tea)8(teaH)12(NO3)12]·8MeCN (where teaH3 = triethanolamine) was synthesised and characterised through single crystal X-ray diffraction and magnetic measurements. The shape of the magnetic hysteresis in the microSQUID measurements was rationalised using the MAGELLAN program.
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Even among genetically identical cancer cells, resistance to therapy frequently emerges from a small subset of those cells1-7. Molecular differences in rare individual cells in the initial population enable certain cells to become resistant to therapy7-9; however, comparatively little is known about the variability in the resistance outcomes. Here we develop and apply FateMap, a framework that combines DNA barcoding with single-cell RNA sequencing, to reveal the fates of hundreds of thousands of clones exposed to anti-cancer therapies. We show that resistant clones emerging from single-cell-derived cancer cells adopt molecularly, morphologically and functionally distinct resistant types. These resistant types are largely predetermined by molecular differences between cells before drug addition and not by extrinsic factors. Changes in the dose and type of drug can switch the resistant type of an initial cell, resulting in the generation and elimination of certain resistant types. Samples from patients show evidence for the existence of these resistant types in a clinical context. We observed diversity in resistant types across several single-cell-derived cancer cell lines and cell types treated with a variety of drugs. The diversity of resistant types as a result of the variability in intrinsic cell states may be a generic feature of responses to external cues.
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Antineoplásicos , Células Clonais , Resistencia a Medicamentos Antineoplásicos , Neoplasias , Humanos , Células Clonais/efeitos dos fármacos , Células Clonais/metabolismo , Células Clonais/patologia , Código de Barras de DNA Taxonômico , Resistencia a Medicamentos Antineoplásicos/efeitos dos fármacos , Resistencia a Medicamentos Antineoplásicos/genética , Neoplasias/tratamento farmacológico , Neoplasias/genética , Neoplasias/patologia , RNA-Seq , Análise da Expressão Gênica de Célula Única , Células Tumorais Cultivadas , Antineoplásicos/farmacologiaRESUMO
The synthesis, structural, and magnetic characterization of [FeIII4LnIII4(teaH)8(N3)8(H2O)] (Ln = Gd and Y) and the previously reported isostructural Dy analogue are discussed. The commonly held belief that both FeIII and GdIII can be regarded as isotropic ions is shown to be an oversimplification. This conclusion is derived from the magnetic data for the YIII analogue in terms of the zero-field splitting seen for FeIII and from the fact that the magnetic data for the new GdIII analogue can only be fit employing an additional anisotropy term for the GdIII ions. Furthermore, the Fe4Gd4 ring shows slow relaxation of magnetization. Our analysis of the experimental magnetic data employs both density functional theory as well as the finite-temperature Lanczos method which finally enables us to provide an almost perfect fit of magnetocaloric properties.
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The [Gd8(opch)8(CO3)4(H2O)8]·4H2O·10MeCN coordination cluster (1) crystallises in P1¯. The Gd8 core is held together by four bridging carbonates derived from atmospheric CO2 as well as the carboxyhydrazonyl oxygens of the 2-hydroxy-3-methoxybenzylidenepyrazine-2-carbohydrazide (H2opch) Schiff base ligands. The magnetic measurements show that the GdIII ions are effectively uncoupled as seen from the low Weiss constant of 0.05 K needed to fit the inverse susceptibility to the Curie-Weiss law. Furthermore, the magnetisation data are consistent with the Brillouin function for eight independent GdIII ions. These features lead to a magnetocaloric effect with a high efficiency which is 89% of the theoretical maximum value.
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Dióxido de Carbono , Oxigênio , ÍonsRESUMO
The dynamics and connectivity of neural circuits continuously change on timescales ranging from milliseconds to an animal's lifetime. Therefore, to understand biological networks, minimally invasive methods are required to repeatedly record them in behaving animals. Here we describe a suite of devices that enable long-term optical recordings of the adult Drosophila melanogaster ventral nerve cord (VNC). These consist of transparent, numbered windows to replace thoracic exoskeleton, compliant implants to displace internal organs, a precision arm to assist implantation, and a hinged stage to repeatedly tether flies. To validate and illustrate our toolkit we (i) show minimal impact on animal behavior and survival, (ii) follow the degradation of chordotonal organ mechanosensory nerve terminals over weeks after leg amputation, and (iii) uncover waves of neural activity caffeine ingestion. Thus, our long-term imaging toolkit opens up the investigation of premotor and motor circuit adaptations in response to injury, drug ingestion, aging, learning, and disease.
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Proteínas de Drosophila , Drosophila , Animais , Comportamento Animal , Diagnóstico por Imagem , Drosophila/metabolismo , Proteínas de Drosophila/metabolismo , Drosophila melanogaster/metabolismoRESUMO
Objective. To study the neural control of movement, it is often necessary to estimate how muscles are activated across a variety of behavioral conditions. One approach is to try extracting the underlying neural command signal to muscles by applying latent variable modeling methods to electromyographic (EMG) recordings. However, estimating the latent command signal that underlies muscle activation is challenging due to its complex relation with recorded EMG signals. Common approaches estimate each muscle's activation independently or require manual tuning of model hyperparameters to preserve behaviorally-relevant features.Approach. Here, we adapted AutoLFADS, a large-scale, unsupervised deep learning approach originally designed to de-noise cortical spiking data, to estimate muscle activation from multi-muscle EMG signals. AutoLFADS uses recurrent neural networks to model the spatial and temporal regularities that underlie multi-muscle activation.Main results. We first tested AutoLFADS on muscle activity from the rat hindlimb during locomotion and found that it dynamically adjusts its frequency response characteristics across different phases of behavior. The model produced single-trial estimates of muscle activation that improved prediction of joint kinematics as compared to low-pass or Bayesian filtering. We also applied AutoLFADS to monkey forearm muscle activity recorded during an isometric wrist force task. AutoLFADS uncovered previously uncharacterized high-frequency oscillations in the EMG that enhanced the correlation with measured force. The AutoLFADS-inferred estimates of muscle activation were also more closely correlated with simultaneously-recorded motor cortical activity than were other tested approaches.Significance.This method leverages dynamical systems modeling and artificial neural networks to provide estimates of muscle activation for multiple muscles. Ultimately, the approach can be used for further studies of multi-muscle coordination and its control by upstream brain areas, and for improving brain-machine interfaces that rely on myoelectric control signals.
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Aprendizado Profundo , Animais , Teorema de Bayes , Eletromiografia/métodos , Locomoção , Músculo Esquelético/fisiologia , RatosRESUMO
Copper complexes have shown great versatility and a wide application range across the natural and life sciences, with a particular promise as organic light-emitting diodes. In this work, four novel heteroleptic Cu(I) complexes were designed in order to allow their integration in advanced materials such as metallopolymers. We herein present the synthesis and the electrochemical and photophysical characterisation of these Cu(I) complexes, in combination with ab initio calculations. The complexes present a bright cyan emission (λem ~ 505 nm) in their solid state, both as powder and as blends in a polymer matrix. The successful synthesis of metallopolymers embedding two of the novel complexes is shown. These copolymers were also found to be luminescent and their photophysical properties were compared to those of their polymer blends. The chemical nature of the polymer backbone contributes significantly to the photoluminescence quantum yield, paving a route for the strategic design of novel luminescent Cu(I)-based polymeric materials.
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BACKGROUND: Hashtags are widely used for communication in online media. As a condensed version of information, they characterize topics and discussions. For their analysis, we apply methods from network science and propose novel tools for tracing their dynamics in time-dependent data. The observations are characterized by bursty behaviors in the increases and decreases of hashtag usage. These features can be reproduced with a novel model of dynamic rankings. HASHTAG COMMUNITIES IN TIME: We build temporal and weighted co-occurrence networks from hashtags. On static snapshots, we infer the community structure using customized methods. On temporal networks, we solve the bipartite matching problem of detected communities at subsequent timesteps by taking into account higher-order memory. This results in a matching protocol that is robust toward temporal fluctuations and instabilities of the static community detection. The proposed methodology is broadly applicable and its outcomes reveal the temporal behavior of online topics. MODELING TOPIC-DYNAMICS: We consider the size of the communities in time as a proxy for online popularity dynamics. We find that the distributions of gains and losses, as well as the interevent times are fat-tailed indicating occasional, but large and sudden changes in the usage of hashtags. Inspired by typical website designs, we propose a stochastic model that incorporates a ranking with respect to a time-dependent prestige score. This causes occasional cascades of rank shift events and reproduces the observations with good agreement. This offers an explanation for the observed dynamics, based on characteristic elements of online media.
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OBJECTIVE: The objective of this work is to present gumpy, a new free and open source Python toolbox designed for hybrid brain-computer interface (BCI). APPROACH: Gumpy provides state-of-the-art algorithms and includes a rich selection of signal processing methods that have been employed by the BCI community over the last 20 years. In addition, a wide range of classification methods that span from classical machine learning algorithms to deep neural network models are provided. Gumpy can be used for both EEG and EMG biosignal analysis, visualization, real-time streaming and decoding. RESULTS: The usage of the toolbox was demonstrated through two different offline example studies, namely movement prediction from EEG motor imagery, and the decoding of natural grasp movements with the applied finger forces from surface EMG (sEMG) signals. Additionally, gumpy was used for real-time control of a robot arm using steady-state visually evoked potentials (SSVEP) as well as for real-time prosthetic hand control using sEMG. Overall, obtained results with the gumpy toolbox are comparable or better than previously reported results on the same datasets. SIGNIFICANCE: Gumpy is a free and open source software, which allows end-users to perform online hybrid BCIs and provides different techniques for processing and decoding of EEG and EMG signals. More importantly, the achieved results reveal that gumpy's deep learning toolbox can match or outperform the state-of-the-art in terms of accuracy. This can therefore enable BCI researchers to develop more robust decoding algorithms using novel techniques and hence chart a route ahead for new BCI improvements.