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\"Written with undergraduate students in mind, the new edition of this classic textbook provides a compact introduction to the physiology of nerve and muscle. It gives a straightforward account of the fundamentals accompanied by some of the experimental evidence upon which this understanding is based. It first explores the nature of nerve impulses, clarifying their mechanisms in terms of ion flow through molecular channels in cell membranes. There then follows an account of the synaptic transmission processes by which one excitable cell influences activity in another. Finally, the emphasis turns to the consequences of excitable activity in the activation of contraction in skeletal, cardiac and smooth muscle, highlighting the relationships between cellular structure and function. This fourth edition includes new material on the molecular nature of ion channels, the activation of skeletal muscle and the function of cardiac and smooth muscle, reflecting exciting new developments in these rapidly growing fields\"-- Provided by publisher.

Epithelial–mesenchymal transition (EMT) encompasses dynamic changes in cellular organization from epithelial to mesenchymal phenotypes, which leads to functional changes in cell migration and invasion. EMT occurs in a diverse range of physiological and pathological conditions and is driven by a conserved set of inducing signals, transcriptional regulators and downstream effectors. With over 5,700 publications indexed by Web of Science in 2019 alone, research on EMT is expanding rapidly. This growing interest warrants the need for a consensus among researchers when referring to and undertaking research on EMT. This Consensus Statement, mediated by ‘the EMT International Association’ (TEMTIA), is the outcome of a 2-year-long discussion among EMT researchers and aims to both clarify the nomenclature and provide definitions and guidelines for EMT research in future publications. We trust that these guidelines will help to reduce misunderstanding and misinterpretation of research data generated in various experimental models and to promote cross-disciplinary collaboration to identify and address key open questions in this research field. While recognizing the importance of maintaining diversity in experimental approaches and conceptual frameworks, we emphasize that lasting contributions of EMT research to increasing our understanding of developmental processes and combatting cancer and other diseases depend on the adoption of a unified terminology to describe EMT.In this Consensus Statement, the authors (on behalf of the EMT International Association) propose guidelines to define epithelial–mesenchymal transition, its phenotypic plasticity and the associated multiple intermediate epithelial–mesenchymal cell states. Clarification of nomenclature and definitions will help reduce misinterpretation of research data generated in different experimental model systems and promote cross-disciplinary collaboration.

Two major classes of inhibitory neurons in mouse anterior cingulate cortex, somatostatin and parvalbumin interneurons, form functionally homogeneous populations that are recruited at distinct moments in time and encode unique behavioral variables in a foraging task. Neuronal diversity in the cerebral cortex The cerebral cortex contains many different classes of inhibitory interneurons, each with different anatomical and physiological properties. Recent technological developments make it possible to determine the functional impact of individual classes. This optogenetic tagging study of mice performing a reward foraging task shows that parvalbumin- and somatostatin-expressing cells, two of largest interneuron populations, respond differently during different phases of the task. These findings suggest a link between circuit-level activity of the different interneuron types in regulating the flow of information flow and the behavioural functions served by the cortical circuits. Neurons in the prefrontal cortex exhibit diverse behavioural correlates 1 , 2 , 3 , 4 , an observation that has been attributed to cell-type diversity. To link identified neuron types with network and behavioural functions, we recorded from the two largest genetically defined inhibitory interneuron classes, the perisomatically targeting parvalbumin (PV) and the dendritically targeting somatostatin (SOM) neurons 5 , 6 , 7 , 8 in anterior cingulate cortex of mice performing a reward foraging task. Here we show that PV and a subtype of SOM neurons form functionally homogeneous populations showing a double dissociation between both their inhibitory effects and behavioural correlates. Out of several events pertaining to behaviour, a subtype of SOM neurons selectively responded at reward approach, whereas PV neurons responded at reward leaving and encoded preceding stay duration. These behavioural correlates of PV and SOM neurons defined a behavioural epoch and a decision variable important for foraging (whether to stay or to leave), a crucial function attributed to the anterior cingulate cortex 9 , 10 , 11 . Furthermore, PV neurons could fire in millisecond synchrony, exerting fast and powerful inhibition on principal cell firing, whereas the inhibitory effect of SOM neurons on firing output was weak and more variable, consistent with the idea that they respectively control the outputs of, and inputs to, principal neurons 12 , 13 , 14 , 15 , 16 . These results suggest a connection between the circuit-level function of different interneuron types in regulating the flow of information and the behavioural functions served by the cortical circuits. Moreover, these observations bolster the hope that functional response diversity during behaviour can in part be explained by cell-type diversity.

A deep near-infrared spectroscopic survey of 43 photometrically-selected galaxies with redshift z  > 6.5 detects a near-infrared emission line from only a single galaxy; this line is likely to be Lyman α emission at a wavelength of 1.0343 μm, placing this galaxy at z = 7.51. Most distant star-forming galaxy confirmed Hubble Space Telescope data have yielded hundreds of candidates for galaxies with redshifts observed less than one billion years from the Big Bang, but so far distances have been confirmed for only a few of them. Using the newly commissioned MOSFIRE spectrograph on the Keck I telescope, Steven Finkelstein and co-workers have detected a galaxy with an emission line that can be confirmed at a redshift of 7.51, placing it at an epoch 700 million years after the Big Bang. That makes it the most distant spectroscopically confirmed galaxy, This galaxy's colours are consistent with a significant metal content, and it has a surprisingly high star-formation rate of about 330 solar masses per year, more than 100-fold greater than that seen in the Milky Way. The authors suggest that there may be many more such sites of intense star formation in the early Universe than previously expected. Of several dozen galaxies observed spectroscopically that are candidates for having a redshift ( z ) in excess of seven, only five have had their redshifts confirmed via Lyman α emission, at z = 7.008, 7.045, 7.109, 7.213 and 7.215 (refs 1 , 2 , 3 , 4 ). The small fraction of confirmed galaxies may indicate that the neutral fraction in the intergalactic medium rises quickly at z  > 6.5, given that Lyman α is resonantly scattered by neutral gas 3 , 5 , 6 , 7 , 8 . The small samples and limited depth of previous observations, however, makes these conclusions tentative. Here we report a deep near-infrared spectroscopic survey of 43 photometrically-selected galaxies with z  > 6.5. We detect a near-infrared emission line from only a single galaxy, confirming that some process is making Lyman α difficult to detect. The detected emission line at a wavelength of 1.0343 micrometres is likely to be Lyman α emission, placing this galaxy at a redshift z = 7.51, an epoch 700 million years after the Big Bang. This galaxy’s colours are consistent with significant metal content, implying that galaxies become enriched rapidly. We calculate a surprisingly high star-formation rate of about 330 solar masses per year, which is more than a factor of 100 greater than that seen in the Milky Way. Such a galaxy is unexpected in a survey of our size 9 , suggesting that the early Universe may harbour a larger number of intense sites of star formation than expected.

Alloys with ultra-high strength and sufficient ductility are highly desired for modern engineering applications but difficult to develop. Here we report that, by a careful controlling alloy composition, thermomechanical process, and microstructural feature, a Co-Cr-Ni-based medium-entropy alloy (MEA) with a dual heterogeneous structure of both matrix and precipitates can be designed to provide an ultra-high tensile strength of 2.2 GPa and uniform elongation of 13% at ambient temperature, properties that are much improved over their counterparts without the heterogeneous structure. Electron microscopy characterizations reveal that the dual heterogeneous structures are composed of a heterogeneous matrix with both coarse grains (10∼30 μm) and ultra-fine grains (0.5∼2 μm), together with heterogeneous L1 2 -structured nanoprecipitates ranging from several to hundreds of nanometers. The heterogeneous L1 2 nanoprecipitates are fully coherent with the matrix, minimizing the elastic misfit strain of interfaces, relieving the stress concentration during deformation, and playing an active role in enhanced ductility. Improving both strength and ductility simultaneously in structural metals and alloys remains a challenge. Here, the authors design a heterogeneous structure in a Co-Cr-Ni alloy that results in ultrahigh strength and significant uniform elongation.

Our previous study reported that Epstein–Barr virus(EBV)-encoded latent membrane protein 1 (LMP1) could induce development of CD44 +/High stem-like cells in nasopharyngeal carcinoma (NPC). However, the molecular mechanisms that underlie modulation of cancer stem cells (CSCs) in NPC remain unclear. Here, we show that LMP1 induced CSC-like properties through promotion of the expression of epithelial–mesenchymal transition-like cellular markers and through alterations in differentiation markers. Furthermore, LMP1 activated and triggered phosphoinositide 3-kinase/protein kinase B (PI3K/AKT) pathway, which subsequently stimulated expression of CSC markers, development of side population and tumor sphere formation. This suggests that PI3K/AKT pathway has an important role in the induction and maintenance of CSC properties in NPC. Similarly, PI3K/AKT pathway was also activated by phosphorylase in LMP1-induced CD44 +/High cells. In addition, LMP1 greatly increased expression of miR-21 and downregulated expression of the miR-21 target, PTEN. Overexpression of miR-21 by transfection of miR-21 mimics into LMP1-transformed cells led to phosphorylase-mediated activation of the PI3K/AKT pathway and induction of CSCs. On the contrary, phosphorylation of the PI3K/AKT pathway and the expression of CSC were reversed by an miR-21 inhibitor. The specific inhibitor (Ly294002) of PI3K/AKT pathway significantly decreased expression of miR-21 and CSC markers and upregulated the expression of PTEN, which indicates that miR-21 and PTEN are the downstream effectors of PI3K/AKT and that expression of these two effectors are related to the development of NPC CSCs. Taken together, our novel findings indicate that LMP1, PI3K/AKT, miR-21 and PTEN constitute a positive feedback loop and have a key role in LMP1-induced CSCs in NPC.

Carbonaceous particulate matter (PM), comprising black carbon (BC), primary organic aerosol (POA) and secondary organic aerosol (SOA, from atmospheric aging of precursors), is a highly toxic vehicle exhaust component. Therefore, understanding vehicle pollution requires knowledge of both primary emissions, and how these emissions age in the atmosphere. We provide a systematic examination of carbonaceous PM emissions and parameterisation of SOA formation from modern diesel and gasoline cars at different temperatures (22, −7 °C) during controlled laboratory experiments. Carbonaceous PM emission and SOA formation is markedly higher from gasoline than diesel particle filter (DPF) and catalyst-equipped diesel cars, more so at −7 °C, contrasting with nitrogen oxides (NO X ). Higher SOA formation from gasoline cars and primary emission reductions for diesels implies gasoline cars will increasingly dominate vehicular total carbonaceous PM, though older non-DPF-equipped diesels will continue to dominate the primary fraction for some time. Supported by state-of-the-art source apportionment of ambient fossil fuel derived PM, our results show that whether gasoline or diesel cars are more polluting depends on the pollutant in question, i.e. that diesel cars are not necessarily worse polluters than gasoline cars.

The search continues for nickel oxide-based materials with electronic properties similar to cuprate high-temperature superconductors 1 – 10 . The recent discovery of superconductivity in the doped infinite-layer nickelate NdNiO 2 (refs. 11 , 12 ) has strengthened these efforts. Here, we use X-ray spectroscopy and density functional theory to show that the electronic structure of LaNiO 2 and NdNiO 2 , while similar to the cuprates, includes significant distinctions. Unlike cuprates, the rare-earth spacer layer in the infinite-layer nickelate supports a weakly interacting three-dimensional 5 d metallic state, which hybridizes with a quasi-two-dimensional, strongly correlated state with 3 d x 2 − y 2 symmetry in the NiO 2 layers. Thus, the infinite-layer nickelate can be regarded as a sibling of the rare-earth intermetallics 13 – 15 , which are well known for heavy fermion behaviour, where the NiO 2 correlated layers play an analogous role to the 4 f states in rare-earth heavy fermion compounds. This Kondo- or Anderson-lattice-like ‘oxide-intermetallic’ replaces the Mott insulator as the reference state from which superconductivity emerges upon doping. X-ray spectroscopy and density functional theory are used to show that the electronic structure of the parent compound of superconducting infinite-layer nickelates, while similar to the copper-based high-temperature superconductors, has significant differences.

High-temperature superconductivity emerges on doping holes or electrons into antiferromagnetic copper oxides. The large energy scale of magnetic excitations, for example, compared with phonon energies, is thought to drive superconductivity with high transition temperatures ( T c ). Comparing high-energy magnetic excitations of hole- and electron-doped superconductors provides an opportunity to test this hypothesis. Here, we use resonant inelastic X-ray scattering at the Cu L 3 -edge to reveal collective excitations in the electron-doped cuprate Nd 2− x Ce x CuO 4 . Surprisingly, magnetic excitations harden significantly across the antiferromagnetic high-temperature superconductivity phase boundary despite short-ranged antiferromagnetic correlations, in contrast to the hole-doped cuprates. Furthermore, we find an unexpected branch of collective modes in superconducting compounds, absent in hole-doped cuprates. These modes emanate from the zone centre and possess a higher temperature scale than T c , signalling a distinct quantum phase. Despite their differences, the persistence of magnetic excitations and the existence of a distinct quantum phase are apparently universal in both hole- and electron-doped cuprates. Cuprate superconductors are created by adding electrons or holes to a ‘parent’ compound. They have dissimilar phase diagrams and the asymmetry is further highlighted by unexpected collective modes measured using resonant inelastic X-ray scattering.

Noninvasive deep brain stimulation is an important goal in neuroscience and neuroengineering. Optogenetics normally requires the use of a blue laser inserted into the brain. Chen et al. used specialized nanoparticles that can upconvert near-infrared light from outside the brain into the local emission of blue light (see the Perspective by Feliu et al. ). They injected these nanoparticles into the ventral tegmental area of the mouse brain and activated channelrhodopsin expressed in dopaminergic neurons with near-infrared light generated outside the skull at a distance of several millimeters. This technique allowed distant near-infrared light to evoke fast increases in dopamine release. The method was also used successfully to evoke fear memories in the dentate gyrus during fear conditioning. Science , this issue p. 679 ; see also p. 633 Optogenetic experiments can be performed inside the mouse brain by using near-infrared light applied outside the skull. Optogenetics has revolutionized the experimental interrogation of neural circuits and holds promise for the treatment of neurological disorders. It is limited, however, because visible light cannot penetrate deep inside brain tissue. Upconversion nanoparticles (UCNPs) absorb tissue-penetrating near-infrared (NIR) light and emit wavelength-specific visible light. Here, we demonstrate that molecularly tailored UCNPs can serve as optogenetic actuators of transcranial NIR light to stimulate deep brain neurons. Transcranial NIR UCNP-mediated optogenetics evoked dopamine release from genetically tagged neurons in the ventral tegmental area, induced brain oscillations through activation of inhibitory neurons in the medial septum, silenced seizure by inhibition of hippocampal excitatory cells, and triggered memory recall. UCNP technology will enable less-invasive optical neuronal activity manipulation with the potential for remote therapy.