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Frequency-Dependent Block of Excitatory Neurotransmission by Isoflurane via Dual Presynaptic Mechanisms
Get PDFVolatile anesthetics are widely used for surgery, but neuronal mechanisms of anesthesia remain unidentified. At the calyx of Held in brainstem slices from rats of either sex, isoflurane at clinical doses attenuated EPSCs by decreasing the release probability and the number of readily releasable vesicles. In presynaptic recordings of Ca(2+) currents and exocytic capacitance changes, isoflurane attenuated exocytosis by inhibiting Ca(2+) currents evoked by a short presynaptic depolarization, whereas it inhibited exocytosis evoked by a prolonged depolarization via directly blocking exocytic machinery downstream of Ca(2+) influx. Since the length of presynaptic depolarization can simulate the frequency of synaptic inputs, isoflurane anesthesia is likely mediated by distinct dual mechanisms, depending on input frequencies. In simultaneous presynaptic and postsynaptic action potential recordings, isoflurane impaired the fidelity of repetitive spike transmission, more strongly at higher frequencies. Furthermore, in the cerebrum of adult mice, isoflurane inhibited monosynaptic corticocortical spike transmission, preferentially at a higher frequency. We conclude that dual presynaptic mechanisms operate for the anesthetic action of isoflurane, of which direct inhibition of exocytic machinery plays a low-pass filtering role in spike transmission at central excitatory synapses.SIGNIFICANCE STATEMENT Synaptic mechanisms of general anesthesia remain unidentified. In rat brainstem slices, isoflurane inhibits excitatory transmitter release by blocking presynaptic Ca(2+) channels and exocytic machinery, with the latter mechanism predominating in its inhibitory effect on high-frequency transmission. Both in slice and in vivo, isoflurane preferentially inhibits spike transmission induced by high-frequency presynaptic inputs. This low-pass filtering action of isoflurane likely plays a significant role in general anesthesia.journal articl
Morphogenetic mechanisms forming the notochord rod: The turgor pressure‐sheath strength model
Get PDFThe notochord is a defining feature of chordates. During notochord formation in vertebrates and tunicates, notochord cells display dynamic morphogenetic movement, called convergent extension, in which cells intercalate and align at the dorsal midline. However, in cephalochordates, the most basal group of chordates, the notochord is formed without convergent extension. It is simply developed from mesodermal cells at the dorsal midline. This suggests that convergent extension movement of notochord cells is a secondarily acquired developmental attribute in the common ancestor of olfactores (vertebrates + tunicates), and that the chordate ancestor innovated the notochord upon a foundation of morphogenetic mechanisms independent of cell movement. Therefore, this review focuses on biological features specific to notochord cells, which have been well studied using clawed frogs, zebrafish, and tunicates. Attributes of notochord cells, such as vacuolation, membrane trafficking, extracellular matrix formation, and apoptosis, can be understood in terms of two properties: turgor pressure of vacuoles and strength of the notochord sheath. To maintain the straight rod-like structure of the notochord, these parameters must be counterbalanced. In the future, the turgor pressure-sheath strength model, proposed in this review, will be examined in light of quantitative molecular data and mathematical simulations, illuminating the evolutionary origin of the notochord.journal articl
Stochastic thermodynamics: experiment and theory
Get PDFStochastic thermodynamics describes the non-equilibrium behavior of mesoscopic physical systems and has emerged as a well-defined subfield of statistical physics during the last few decades. Nowadays, there exists a vibrant community of statistical physicists working in stochastic thermodynamics. While much of the initial progress in this field was theoretical or focused on thought experiments such as the celebrated Maxwell demon, impressive technological advances in recent years have enabled tests of many of the fundamental principles.
The workshop Stochastic Thermodynamics: Experiment and Theory, held at the Max-Planck Institute for Complex Systems in Dresden, 10–14 September 2018, had as a primary goal to bring together theorists and experimentalists to discuss the state of the art stochastic thermodynamics and the main future challenges. The workshop was characterized by a vibrant atmosphere, with participants from all over the world sharing their views on the latest results and the outstanding open questions in this field. Many of these discussions have resulted in novel collaborations and significant steps forward.
This special edition of Journal of Statistical Mechanics: Theory and Experiment collects the outcome of these discussions.journal articl
Rapid and cost-effective generation of single specimen multilocus barcoding data from whole arthropod communities by multiple levels of multiplexing
Get PDFIn light of the current biodiversity crisis, molecular barcoding has developed into an irreplaceable tool. Barcoding has been considerably simplified by developments in high throughput sequencing technology, but still can be prohibitively expensive and laborious when community samples of thousands of specimens need to be processed. Here, we outline an Illumina amplicon sequencing approach to generate multilocus data from large collections of arthropods. We reduce cost and effort up to 50-fold, by combining multiplex PCRs and DNA extractions from pools of presorted and morphotyped specimens and using two levels of sample indexing. We test our protocol by generating a comprehensive, community wide dataset of barcode sequences for several thousand Hawaiian arthropods from 14 orders, which were collected across the archipelago using various trapping methods. We explore patterns of diversity across the Archipelago and compare the utility of different arthropod trapping methods for biodiversity explorations on Hawaii, highlighting undergrowth beating as highly efficient method. Moreover, we show the effects of barcode marker, taxonomy and relative biomass of the targeted specimens and sequencing coverage on taxon recovery. Our protocol enables rapid and inexpensive explorations of diversity patterns and the generation of multilocus barcode reference libraries across whole ecosystems.journal articl
Lightcone expansions of conformal blocks in closed form
Get PDFWe present new closed-form expressions for 4-point scalar conformal blocks in the s- and t-channel lightcone expansions. Our formulae apply to intermediate operators of arbitrary spin in general dimensions. For physical spin `, they are composed of at most (ℓ+ 1) Gaussian hypergeometric functions at each order.journal articl
COVID-19 Disease Map, building a computational repository of SARS-CoV-2 virus-host interaction mechanisms
Get PDFResearchers around the world join forces to reconstruct the molecular processes of the virus-host interactions aiming to combat the cause of the ongoing pandemic.journal articl
A Persistent Kuroshio in the Glacial East China Sea and Implications for Coral Paleobiogeography
Get PDFThe Kuroshio Current is a major hydrographical feature of the modern East China Sea, but it has been suggested that its flow was diverted to the east of the Ryukyu Arc at the Last Glacial Maximum. Shoaling of the Yonaguni Depression has also been proposed as a cause of Kuroshio Current diversion which, while unlikely to have been significant at the Last Glacial Maximum, may have been an important consideration further back in time. Using an ensemble of high‐resolution ocean simulations with climatic boundary conditions emulating those of the Last Glacial Maximum, we present the first regional state estimates of the glacial East China Sea which are both physically consistent and compatible with sea surface temperature proxy compilations. We find that while the Kuroshio Current transport in the East China Sea is slightly reduced at the Last Glacial Maximum, its path is relatively unchanged, with limited sensitivity to glacioeustatic sea level change, glacial‐interglacial changes in climate, and tectonic shoaling of the Yonaguni Depression. Simulations with the best model‐proxy agreement predict only limited contraction of the reef front at the Last Glacial Maximum, and strong surface currents associated with the glacial Kuroshio may have maintained or even improved long‐distance coral larval dispersal along the Ryukyu Arc, suggesting that conditions may have enabled coral reefs in this region to remain widespread throughout the last glacial. Further field studies investigating whether this is genuinely the case will provide insights into how the coral reef front responds to long‐term environmental change.journal articl
Pyridoxal 5′-Phosphate-Dependent Enzymes at the Crossroads of Host–Microbe Tryptophan Metabolism
Get PDFThe chemical processes taking place in humans intersects the myriad of metabolic pathways occurring in commensal microorganisms that colonize the body to generate a complex biochemical network that regulates multiple aspects of human life. The role of tryptophan (Trp) metabolism at the intersection between the host and microbes is increasingly being recognized, and multiple pathways of Trp utilization in either direction have been identified with the production of a wide range of bioactive products. It comes that a dysregulation of Trp metabolism in either the host or the microbes may unbalance the production of metabolites with potential pathological consequences. The ability to redirect the Trp flux to restore a homeostatic production of Trp metabolites may represent a valid therapeutic strategy for a variety of pathological conditions, but identifying metabolic checkpoints that could be exploited to manipulate the Trp metabolic network is still an unmet need. In this review, we put forward the hypothesis that pyridoxal 5'-phosphate (PLP)-dependent enzymes, which regulate multiple pathways of Trp metabolism in both the host and in microbes, might represent critical nodes and that modulating the levels of vitamin B6, from which PLP is derived, might represent a metabolic checkpoint to re-orienteer Trp flux for therapeutic purposes.journal articl
Spatially and temporally resolved microscopy of traps in hybrid organic-inorganic perovskites
Get PDFOkinawa Institute of Science and Technology Graduate UniversityDoctor of PhilosophyIn recent years the class of materials known as hybrid organic-inorganic perovskite (HOIP) have received notable attention for use in photovoltaic applications, with record solar conversion eciencies reaching other established thin lm systems. Despite their rapid development, there are still ongoing issues related to heterogeneous lm properties which limit device performance. It has been suggested that sites which capture charge carriers (traps) could be localized on a micrometer or smaller size scale, leading to regions of poor eciency. Understanding the electronic properties of such regions, in particular on how they inuence carrier recombination, will therefore provide crucial information about the carrier loss pathways in HOIP lms, which will be essential for developing new strategies to minimize losses and create more ecient devices. In order to gain information about the ultrafast charge carrier recombination dynamics on nanoscale length scales, specialized techniques which can provide information with both high spatial and temporal resolution will be necessary. Here, we utilize time resolved photoemission electron microscopy (TR-PEEM) as a novel technique to study the nanoscale ultrafast properties of photo excited carriers and their relation to heterogeneous lm properties in HOIP thin lm materials. Following this overall theme, the work in this thesis will address several nanoscale properties and phenomenon. First, we will uncover the nanoscale distribution of carrier traps in a HOIP lm which result in non-radiative losses. We then will describe in depth the ultrafast carrier trapping processes happening at nanoscale trap clusters. Following this, we will then discuss other novel information and studies on the traps in HOIP which can be realized using TR-PEEM, namely on eects of light treatments and morphological information. By gaining a deeper understanding in these directions, we hope to contribute to the broader goal of improving HOIP photovoltaic device eciency and showcase TR-PEEM as a novel technique for studying photocarrier dynamics in semiconductor materials.doctoral thesi
Transcriptome Analyses of Immune System Behaviors in Primary Polyp of Coral Acropora digitifera Exposed to the Bacterial Pathogen Vibrio coralliilyticus under Thermal Loading
Get PDFElevated sea surface temperature associated with global warming is a serious threat to coral reefs. Elevated temperatures directly or indirectly alter the distribution of coral-pathogen interactions and thereby exacerbate infectious coral diseases. The pathogenic bacterium Vibrio coralliilyticus is well-known as a causative agent of infectious coral disease. Rising sea surface temperature promotes the infection of corals by this bacterium, which causes several coral pathologies, such as bacterial bleaching, tissue lysis, and white syndrome. However, the effects of thermal stress on coral immune responses to the pathogen are poorly understood. To delineate the effects of thermal stress on coral immunity, we performed transcriptome analysis of aposymbiotic primary polyps of the reef-building coral Acropora digitifera exposed to V. coralliilyticus under thermal stress conditions. V. coralliilyticus infection of coral that was under thermal stress had negative effects on various molecular processes, including suppression of gene expression related to the innate immune response. In response to the pathogen, the coral mounted various responses including changes in protein metabolism, exosome release delivering signal molecules, extracellular matrix remodeling, and mitochondrial metabolism changes. Based on these results, we provide new insights into innate immunity of A. digitifera against pathogen infection under thermal stress conditions.journal articl