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Cortical pattern generation during dexterous movement is input-driven 期刊论文
NATURE, 2020, 577 (7790) : 386-+
作者:  Cyranoski, David
收藏  |  浏览/下载:9/0  |  提交时间:2020/07/03

The motor cortex controls skilled arm movement by sending temporal patterns of activity to lower motor centres(1). Local cortical dynamics are thought to shape these patterns throughout movement execution(2-4). External inputs have been implicated in setting the initial state of the motor cortex(5,6), but they may also have a pattern-generating role. Here we dissect the contribution of local dynamics and inputs to cortical pattern generation during a prehension task in mice. Perturbing cortex to an aberrant state prevented movement initiation, but after the perturbation was released, cortex either bypassed the normal initial state and immediately generated the pattern that controls reaching or failed to generate this pattern. The difference in these two outcomes was probably a result of external inputs. We directly investigated the role of inputs by inactivating the thalamus  this perturbed cortical activity and disrupted limb kinematics at any stage of the movement. Activation of thalamocortical axon terminals at different frequencies disrupted cortical activity and arm movement in a graded manner. Simultaneous recordings revealed that both thalamic activity and the current state of cortex predicted changes in cortical activity. Thus, the pattern generator for dexterous arm movement is distributed across multiple, strongly interacting brain regions.


  
Temporal Characteristics and Potential Sources of Black Carbon in Megacity Shanghai, China 期刊论文
JOURNAL OF GEOPHYSICAL RESEARCH-ATMOSPHERES, 2020, 125 (9)
作者:  Wei, C.;  Wang, M. H.;  Fu, Q. Y.;  Dai, C.;  Huang, R.;  Bao, Q.
收藏  |  浏览/下载:8/0  |  提交时间:2020/07/02
black carbon  temporal variation  source apportionment  meteorological condition  back trajectory  
Hot moments in ecosystem fluxes: High GPP anomalies exert outsized influence on the carbon cycle and are differentially driven by moisture availability across biomes 期刊论文
ENVIRONMENTAL RESEARCH LETTERS, 2020, 15 (5)
作者:  Kannenberg, Steven A.;  Bowling, David R.;  Anderegg, William R. L.
收藏  |  浏览/下载:15/0  |  提交时间:2020/05/13
carbon uptake  eddy covariance  meteorological variability  temporal heterogeneity  
Field-resolved infrared spectroscopy of biological systems 期刊论文
NATURE, 2020, 577 (7788) : 52-+
作者:  Pupeza, Ioachim;  Huber, Marinus;  Trubetskov, Michael;  Schweinberger, Wolfgang;  Hussain, Syed A.;  Hofer, Christina;  Fritsch, Kilian;  Poetzlberger, Markus;  Vamos, Lenard;  Fill, Ernst;  Amotchkina, Tatiana;  Kepesidis, Kosmas V.;  Apolonski, Alexander;  Karpowicz, Nicholas;  Pervak, Vladimir;  Pronin, Oleg;  Fleischmann, Frank;  Azzeer, Abdallah;  Zigman, Mihaela;  Krausz, Ferenc
收藏  |  浏览/下载:14/0  |  提交时间:2020/07/03

The proper functioning of living systems and physiological phenotypes depends on molecular composition. Yet simultaneous quantitative detection of a wide variety of molecules remains a challenge(1-8). Here we show how broadband optical coherence opens up opportunities for fingerprinting complex molecular ensembles in their natural environment. Vibrationally excited molecules emit a coherent electric field following few-cycle infrared laser excitation(9-12), and this field is specific to the sample'  s molecular composition. Employing electro-optic sampling(10,12-15), we directly measure this global molecular fingerprint down to field strengths 10(7) times weaker than that of the excitation. This enables transillumination of intact living systems with thicknesses of the order of 0.1 millimetres, permitting broadband infrared spectroscopic probing of human cells and plant leaves. In a proof-of-concept analysis of human blood serum, temporal isolation of the infrared electric-field fingerprint from its excitation along with its sampling with attosecond timing precision results in detection sensitivity of submicrograms per millilitre of blood serum and a detectable dynamic range of molecular concentration exceeding 10(5). This technique promises improved molecular sensitivity and molecular coverage for probing complex, real-world biological and medical settings.


  
Internal state dynamics shape brainwide activity and foraging behaviour 期刊论文
NATURE, 2020, 577 (7789) : 239-+
作者:  Marques, Joao C.;  Li, Meng;  Schaak, Diane;  Robson, Drew N.;  Li, Jennifer M.
收藏  |  浏览/下载:6/0  |  提交时间:2020/07/03

The brain has persistent internal states that can modulate every aspect of an animal'  s mental experience(1-4). In complex tasks such as foraging, the internal state is dynamic(5-8). Caenorhabditis elegans alternate between local search and global dispersal(5). Rodents and primates exhibit trade-offs between exploitation and exploration(6,7). However, fundamental questions remain about how persistent states are maintained in the brain, which upstream networks drive state transitions and how state-encoding neurons exert neuromodulatory effects on sensory perception and decision-making to govern appropriate behaviour. Here, using tracking microscopy to monitor whole-brain neuronal activity at cellular resolution in freely moving zebrafish larvae(9), we show that zebrafish spontaneously alternate between two persistent internal states during foraging for live prey (Paramecia). In the exploitation state, the animal inhibits locomotion and promotes hunting, generating small, localized trajectories. In the exploration state, the animal promotes locomotion and suppresses hunting, generating long-ranging trajectories that enhance spatial dispersion. We uncover a dorsal raphe subpopulation with persistent activity that robustly encodes the exploitation state. The exploitation-state-encoding neurons, together with a multimodal trigger network that is associated with state transitions, form a stochastically activated nonlinear dynamical system. The activity of this oscillatory network correlates with a global retuning of sensorimotor transformations during foraging that leads to marked changes in both the motivation to hunt for prey and the accuracy of motor sequences during hunting. This work reveals an important hidden variable that shapes the temporal structure of motivation and decision-making.


  
Population flow drives spatio-temporal distribution of COVID-19 in China 期刊论文
NATURE, 2020
作者:  Fernandez, Diego Carlos;  Komal, Ruchi;  Langel, Jennifer;  Ma, Jun;  Duy, Phan Q.;  Penzo, Mario A.;  Zhao, Haiqing;  Hattar, Samer
收藏  |  浏览/下载:70/0  |  提交时间:2020/07/03

Sudden, large-scale and diffuse human migration can amplify localized outbreaks of disease into widespread epidemics(1-4). Rapid and accurate tracking of aggregate population flows may therefore be epidemiologically informative. Here we use 11,478,484 counts of mobile phone data from individuals leaving or transiting through the prefecture of Wuhan between 1 January and 24 January 2020 as they moved to 296 prefectures throughout mainland China. First, we document the efficacy of quarantine in ceasing movement. Second, we show that the distribution of population outflow from Wuhan accurately predicts the relative frequency and geographical distribution of infections with severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) until 19 February 2020, across mainland China. Third, we develop a spatio-temporal '  risk source'  model that leverages population flow data (which operationalize the risk that emanates from epidemic epicentres) not only to forecast the distribution of confirmed cases, but also to identify regions that have a high risk of transmission at an early stage. Fourth, we use this risk source model to statistically derive the geographical spread of COVID-19 and the growth pattern based on the population outflow from Wuhan  the model yields a benchmark trend and an index for assessing the risk of community transmission of COVID-19 over time for different locations. This approach can be used by policy-makers in any nation with available data to make rapid and accurate risk assessments and to plan the allocation of limited resources ahead of ongoing outbreaks.


Modelling of population flows in China enables the forecasting of the distribution of confirmed cases of COVID-19 and the identification of areas at high risk of SARS-CoV-2 transmission at an early stage.


  
An acute immune response underlies the benefit of cardiac stem cell therapy 期刊论文
NATURE, 2020, 577 (7790) : 405-+
作者:  Schmacke, Niklas A.;  Hornung, Veit
收藏  |  浏览/下载:20/0  |  提交时间:2020/07/03

Clinical trials using adult stem cells to regenerate damaged heart tissue continue to this day(1,2), despite ongoing questions of efficacy and a lack of mechanistic understanding of the underlying biological effect(3). The rationale for these cell therapy trials is derived from animal studies that show a modest but reproducible improvement in cardiac function in models of cardiac ischaemic injury(4,5). Here we examine the mechanistic basis for cell therapy in mice after ischaemia-reperfusion injury, and find that-although heart function is enhanced-it is not associated with the production of new cardiomyocytes. Cell therapy improved heart function through an acute sterile immune response characterized by the temporal and regional induction of CCR2(+) and CX3CR1(+) macrophages. Intracardiac injection of two distinct types of adult stem cells, cells killed by freezing and thawing or a chemical inducer of the innate immune response all induced a similar regional accumulation of CCR2(+) and CX3CR1(+) macrophages, and provided functional rejuvenation to the heart after ischaemia-reperfusion injury. This selective macrophage response altered the activity of cardiac fibroblasts, reduced the extracellular matrix content in the border zone and enhanced the mechanical properties of the injured area. The functional benefit of cardiac cell therapy is thus due to an acute inflammatory-based wound-healing response that rejuvenates the infarcted area of the heart.


  
APOE4 leads to blood-brain barrier dysfunction predicting cognitive decline 期刊论文
NATURE, 2020, 581 (7806) : 70-+
作者:  Doherty, Tiarnan A. S.;  Winchester, Andrew J.;  Macpherson, Stuart;  Johnstone, Duncan N.;  Pareek, Vivek;  Tennyson, Elizabeth M.;  Kosar, Sofiia;  Kosasih, Felix U.;  Anaya, Miguel;  Abdi-Jalebi, Mojtaba;  Andaji-Garmaroudi, Zahra;  Wong, E. Laine;  Madeo, Julien;  Chiang, Yu-Hsien;  Park, Ji-Sang;  Jung, Young-Kwang;  Petoukhoff, Christopher E.;  Divitini, Giorgio;  Man, Michael K. L.;  Ducati, Caterina;  Walsh, Aron;  Midgley, Paul A.;  Dani, Keshav M.;  Stranks, Samuel D.
收藏  |  浏览/下载:25/0  |  提交时间:2020/07/03

Breakdown of the blood-brain barrier in individuals carrying the epsilon 4 allele of the APOE gene, but not the epsilon 3 allele, increases with and predicts cognitive impairment and is independent of amyloid beta or tau pathology.


Vascular contributions to dementia and Alzheimer'  s disease are increasingly recognized(1-6). Recent studies have suggested that breakdown of the blood-brain barrier (BBB) is an early biomarker of human cognitive dysfunction(7), including the early clinical stages of Alzheimer'  s disease(5,8-10). The E4 variant of apolipoprotein E (APOE4), the main susceptibility gene for Alzheimer'  s disease(11-14), leads to accelerated breakdown of the BBB and degeneration of brain capillary pericytes(15-19), which maintain BBB integrity(20-22). It is unclear, however, whether the cerebrovascular effects of APOE4 contribute to cognitive impairment. Here we show that individuals bearing APOE4 (with the epsilon 3/epsilon 4 or epsilon 4/epsilon 4 alleles) are distinguished from those without APOE4 (epsilon 3/epsilon 3) by breakdown of the BBB in the hippocampus and medial temporal lobe. This finding is apparent in cognitively unimpaired APOE4 carriers and more severe in those with cognitive impairment, but is not related to amyloid-beta or tau pathology measured in cerebrospinal fluid or by positron emission tomography(23). High baseline levels of the BBB pericyte injury biomarker soluble PDGFR beta(7,8) in the cerebrospinal fluid predicted future cognitive decline in APOE4 carriers but not in non-carriers, even after controlling for amyloid-beta and tau status, and were correlated with increased activity of the BBB-degrading cyclophilin A-matrix metalloproteinase-9 pathway(19) in cerebrospinal fluid. Our findings suggest that breakdown of the BBB contributes to APOE4-associated cognitive decline independently of Alzheimer'  s disease pathology, and might be a therapeutic target in APOE4 carriers.


  
Methane emissions from underground gas storage in California 期刊论文
ENVIRONMENTAL RESEARCH LETTERS, 2020, 15 (4)
作者:  Thorpe, Andrew K.;  Duren, Riley M.;  Conley, Stephen;  Prasad, Kuldeep R.;  Bue, Brian D.;  Yadav, Vineet;  Foster, Kelsey T.;  Rafiq, Talha;  Hopkins, Francesca M.;  Smith, Mackenzie L.;  Fischer, Marc L.;  Thompson, David R.;  Frankenberg, Christian;  McCubbin, Ian B.;  Eastwood, Michael L.;  Green, Robert O.;  Miller, Charles E.
收藏  |  浏览/下载:12/0  |  提交时间:2020/07/02
methane  emissions  underground gas storage  Aliso Canyon  temporal variability  imaging spectrometer  
Frequency-Dependent Behavior of Zonal Jet Variability 期刊论文
GEOPHYSICAL RESEARCH LETTERS, 2020, 47 (6)
作者:  Lindgren, Erik A.;  Sheshadri, Aditi;  Plumb, R. Alan
收藏  |  浏览/下载:8/0  |  提交时间:2020/07/02
Storm tracks  Southern Annular Mode  Jet shift  Low-frequency behavior  Temporal filter