Sample records for nakamura masayoshi soma

  1. Generalized trajectory surface hopping method based on the Zhu-Nakamura theory

    NASA Astrophysics Data System (ADS)

    Oloyede, Ponmile; Mil'nikov, Gennady; Nakamura, Hiroki

    2006-04-01

    We present a generalized formulation of the trajectory surface hopping method applicable to a general multidimensional system. The method is based on the Zhu-Nakamura theory of a nonadiabatic transition and therefore includes the treatment of classically forbidden hops. The method uses a generalized recipe for the conservation of angular momentum after forbidden hops and an approximation for determining a nonadiabatic transition direction which is crucial when the coupling vector is unavailable. This method also eliminates the need for a rigorous location of the seam surface, thereby ensuring its applicability to a wide class of chemical systems. In a test calculation, we implement the method for the DH2+ system, and it shows a remarkable agreement with the previous results of C. Zhu, H. Kamisaka, and H. Nakamura, [J. Chem. Phys. 116, 3234 (2002)]. We then apply it to a diatomic-in-molecule model system with a conical intersection, and the results compare well with exact quantum calculations. The successful application to the conical intersection system confirms the possibility of directly extending the present method to an arbitrary potential of general topology.

  2. On the colour types in Lycodes nakamurae (Tanaka, 1914) and species composition of the subgenus Furcimanus (Perciformes: Zoarcidae: Lycodes) in the sea of Japan.

    PubMed

    Saveliev, Pavel A; Balanov, Andrey A; Kukhlevskii, Andrey D

    2014-05-30

    Two colour types were revealed in a zoarcid fish of the subgenus Furcimanus, genus Lycodes, in the Sea of Japan. A comparison of morphometric, meristic and genetic characters in dark coloured and light coloured individuals suggests that the two colour morphs represent a single species, determined to be Lycodes nakamurae (Tanaka, 1914). Variability in colouration within L. nakamurae and a lack of morphological or molecular characters distinguishing L. nakamurae from L. nishimurai Shinohara & Shirai, 2005 suggest that the latter should be considered a synonym of L. nakamurae (Tanaka, 1914). A record of L. pectoralis in the waters of the Republic of Korea is regarded as a misidentification. Thus, we conclude that only one species of the Lycodes subgenus Furcimanus, L. nakamurae, with dark and light colour morphs as well as specimens of intermediate colouration, inhabits the Sea of Japan.

  3. SOMA AS ENERGIZER-CUM-EUPHORIANT, VERSUS SURA, AN INTOXICANT

    PubMed Central

    Mahdihassan, S.

    1984-01-01

    Specific features of Soma plant are implict from various references in Rigveda enabling its identity as ephedra. Its juice is an energizer – cum – euphoriant contrary to the intoxicant sura. Sura is beer prepared from barely malt. Soma is the juice of ephedra rich in ephedrine which is antisomnalent. At least one use of soma has never been substituted, as the drink of longevity for a newly born child. PMID:22557400

  4. Soma of the Rigveda and an attempt to identify it.

    PubMed

    Mahdihassan, S; Mehdi, F S

    1989-01-01

    Ephedra juice is used as the drink of longevity given even to the new born. This is an Aryan custom mentioned in Rigveda and followed even by the Romans. To trace the history of this custom would lead to identifying Soma = Ephedra. The original species of Ephedra or Soma proper would be Ephedra sinica, the Chinese plant. It is the one species with yellow stalks. This has been illustrated so that it confirms Rigveda speaking of Soma as "golden yellow." The name Soma is also a loan word from Chinese meaning "fire-yellow fibers of hemp." The plant Soma is described as "thousand boughs" and photographic evidence has been offered in support. Each stalk is rod-like resembling an arrow as Rigveda speaks of it. An illustration has been offered to show the plant with stalks which are straight and rod-like, comparable with an arrow.

  5. Bi-directional gap junction-mediated soma-germline communication is essential for spermatogenesis.

    PubMed

    Smendziuk, Christopher M; Messenberg, Anat; Vogl, A Wayne; Tanentzapf, Guy

    2015-08-01

    Soma-germline interactions play conserved essential roles in regulating cell proliferation, differentiation, patterning and homeostasis in the gonad. In the Drosophila testis, secreted signalling molecules of the JAK-STAT, Hedgehog, BMP and EGF pathways are used to mediate soma-germline communication. Here, we demonstrate that gap junctions may also mediate direct, bi-directional signalling between the soma and germ line. When gap junctions between the soma and germ line are disrupted, germline differentiation is blocked and germline stem cells are not maintained. In the soma, gap junctions are required to regulate proliferation and differentiation. Localization and RNAi-mediated knockdown studies reveal that gap junctions in the fly testis are heterotypic channels containing Zpg (Inx4) and Inx2 on the germ line and the soma side, respectively. Overall, our results show that bi-directional gap junction-mediated signalling is essential to coordinate the soma and germ line to ensure proper spermatogenesis in Drosophila. Moreover, we show that stem cell maintenance and differentiation in the testis are directed by gap junction-derived cues. © 2015. Published by The Company of Biologists Ltd.

  6. Thunder among the pines: defining a pan-Asian soma.

    PubMed

    Dannaway, Frederick

    2009-03-01

    Many ancient cultures and religions engaged in various techniques and used various substances to instigate religious experience and to alter perception. These techniques of psycho-sexual drug yoga reached an unparalleled level of sophistication that arose and was often cloaked in practical terms of alchemy and metallurgy. The Vedic tradition describes this plant-based ritualism as soma, which has been identified by Gordon Wasson as the mushroom Amanita muscaria. This article traces these soma-influenced sects of esoteric Buddhism that exerted influences from India, China and Tibet to Japan. Some of the key components, practices and symbolism are retained despite numerous cultural filters. Japan's tradition of esoteric Buddhism can thus be seen to have preserved and incorporated the soma/amrita mushroom lore into its own traditions of mountain ascetic mystics.

  7. FURTHER STUDY OF SOMA, DENDRITE, AND AXON EXCITATION IN SINGLE NEURONS

    PubMed Central

    Eyzaguirre, Carlos; Kuffler, Stephen W.

    1955-01-01

    The present investigation continues a previous study in which the soma-dendrite system of sensory neurons was excited by stretch deformation of the peripheral dendrite portions. Recording was done with intracellular leads which were inserted into the cell soma while the neuron was activated orthodromically or antidromically. The analysis was also extended to axon conduction. Crayfish, Procambarus alleni (Faxon) and Orconectes virilis (Hagen), were used. 1. The size and time course of action potentials recorded from the soma-dendrite complex vary greatly with the level of the cell's membrane potential. The latter can be changed over a wide range by stretch deformation which sets up a "generator potential" in the distal portions of the dendrites. If a cell is at its resting unstretched equilibrium potential, antidromic stimulation through the axon causes an impulse which normally overshoots the resting potential and decays into an afternegativity of 15 to 20 msec. duration. The postspike negativity is not followed by an appreciable hyperpolarization (positive) phase. If the membrane potential is reduced to a new steady level a postspike positivity appears and increases linearly over a depolarization range of 12 to 20 mv. in various cells. At those levels the firing threshold of the cell for orthodromic discharges is generally reached. 2. The safety factor for conduction between axon and cell soma is reduced under three unrelated conditions, (a) During the recovery period (2 to 3 msec.) immediately following an impulse which has conducted fully over the cell soma, a second impulse may be delayed, may invade the soma partially, or may be blocked completely. (b) If progressive depolarization is produced by stretch, it leads to a reduction of impulse height and eventually to complete block of antidromic soma invasion, resembling cathodal block, (c) In some cells, when the normal membrane potential is within several millivolts of the relaxed resting state, an antidromic

  8. Revisiting Wasson's Soma: exploring the effects of preparation on the chemistry of Amanita muscaria.

    PubMed

    Feeney, Kevin

    2010-12-01

    In 1968 R. Gordon Wasson first proposed his groundbreaking theory identifying Soma, the hallucinogenic sacrament of the Vedas, as the Amanita muscaria mushroom. While Wasson's theory has garnered acclaim, it is not without its faults. One omission in Wasson's theory is his failure to explain how pressing and filtering Soma, as described in the Rig Veda, supports his theory of Soma's identity. Several critics have reasoned that such preparation should be unnecessary if equivalent results can be obtained by consuming the raw plant, as is done with other psychoactive mushrooms. In order to address these specific criticisms over 600 anecdotal accounts of Amanita muscaria inebriation were collected and analyzed to determine the impact of preparation on Amanita muscaria's effects. The findings of this study demonstrated that the effects of Amanita muscaria were related to the type of preparation employed, and that its toxic effects were considerably reduced by preparations that paralleled those described for Soma in the Rig Veda. While unlikely to end debate over the identity of Soma, this study's findings help to solidify the foundation of Wasson's theory, and also to demonstrate the importance of preparation in understanding and uncovering the true identity of Soma.

  9. A univocal definition of the neuronal soma morphology using Gaussian mixture models.

    PubMed

    Luengo-Sanchez, Sergio; Bielza, Concha; Benavides-Piccione, Ruth; Fernaud-Espinosa, Isabel; DeFelipe, Javier; Larrañaga, Pedro

    2015-01-01

    The definition of the soma is fuzzy, as there is no clear line demarcating the soma of the labeled neurons and the origin of the dendrites and axon. Thus, the morphometric analysis of the neuronal soma is highly subjective. In this paper, we provide a mathematical definition and an automatic segmentation method to delimit the neuronal soma. We applied this method to the characterization of pyramidal cells, which are the most abundant neurons in the cerebral cortex. Since there are no benchmarks with which to compare the proposed procedure, we validated the goodness of this automatic segmentation method against manual segmentation by neuroanatomists to set up a framework for comparison. We concluded that there were no significant differences between automatically and manually segmented somata, i.e., the proposed procedure segments the neurons similarly to how a neuroanatomist does. It also provides univocal, justifiable and objective cutoffs. Thus, this study is a means of characterizing pyramidal neurons in order to objectively compare the morphometry of the somata of these neurons in different cortical areas and species.

  10. Navigating neurites utilize cellular topography of Schwann cell somas and processes for optimal guidance

    PubMed Central

    Lopez-Fagundo, Cristina; Mitchel, Jennifer A.; Ramchal, Talisha D.; Dingle, Yu-Ting L.; Hoffman-Kim, Diane

    2013-01-01

    The path created by aligned Schwann cells (SCs) after nerve injury underlies peripheral nerve regeneration. We developed geometric bioinspired substrates to extract key information needed for axon guidance by deconstructing the topographical cues presented by SCs. We have previously reported materials that directly replicate SC topography with micro- and nanoscale resolution, but a detailed explanation of the means of directed axon extension on SC topography has not yet been described. Here, using neurite tracing and time-lapse microscopy, we analyzed the SC features that influence axon guidance. Novel poly(dimethylsiloxane) materials, fabricated via photolithography, incorporated bioinspired topographical components with the shapes and sizes of aligned SCs, namely somas and processes, where the length of the processes were varied but the soma geometry and dimensions were kept constant. Rat dorsal root ganglia neurites aligned to all materials presenting bioinspired topography after a 5 days in culture and to bioinspired materials presenting soma and process features after only 17 hours in culture. Key findings of this study were: Neurite response to underlying bioinspired topographical features was time dependent, where at 5 days, neurites aligned most strongly to materials presenting combinations of soma and process features, with higher than average density of either process or soma features; but at 17 hours they aligned more strongly to materials presenting average densities of soma and process features and to materials presenting process features only. These studies elucidate the influence of SC topography on axon guidance in a time-dependent setting and have implications for the optimization of nerve regeneration strategies. PMID:23557939

  11. Improved detection of soma location and morphology in fluorescence microscopy images of neurons.

    PubMed

    Kayasandik, Cihan Bilge; Labate, Demetrio

    2016-12-01

    Automated detection and segmentation of somas in fluorescent images of neurons is a major goal in quantitative studies of neuronal networks, including applications of high-content-screenings where it is required to quantify multiple morphological properties of neurons. Despite recent advances in image processing targeted to neurobiological applications, existing algorithms of soma detection are often unreliable, especially when processing fluorescence image stacks of neuronal cultures. In this paper, we introduce an innovative algorithm for the detection and extraction of somas in fluorescent images of networks of cultured neurons where somas and other structures exist in the same fluorescent channel. Our method relies on a new geometrical descriptor called Directional Ratio and a collection of multiscale orientable filters to quantify the level of local isotropy in an image. To optimize the application of this approach, we introduce a new construction of multiscale anisotropic filters that is implemented by separable convolution. Extensive numerical experiments using 2D and 3D confocal images show that our automated algorithm reliably detects somas, accurately segments them, and separates contiguous ones. We include a detailed comparison with state-of-the-art existing methods to demonstrate that our algorithm is extremely competitive in terms of accuracy, reliability and computational efficiency. Our algorithm will facilitate the development of automated platforms for high content neuron image processing. A Matlab code is released open-source and freely available to the scientific community. Copyright © 2016 Elsevier B.V. All rights reserved.

  12. Power Laws from Linear Neuronal Cable Theory: Power Spectral Densities of the Soma Potential, Soma Membrane Current and Single-Neuron Contribution to the EEG

    PubMed Central

    Pettersen, Klas H.; Lindén, Henrik; Tetzlaff, Tom; Einevoll, Gaute T.

    2014-01-01

    Power laws, that is, power spectral densities (PSDs) exhibiting behavior for large frequencies f, have been observed both in microscopic (neural membrane potentials and currents) and macroscopic (electroencephalography; EEG) recordings. While complex network behavior has been suggested to be at the root of this phenomenon, we here demonstrate a possible origin of such power laws in the biophysical properties of single neurons described by the standard cable equation. Taking advantage of the analytical tractability of the so called ball and stick neuron model, we derive general expressions for the PSD transfer functions for a set of measures of neuronal activity: the soma membrane current, the current-dipole moment (corresponding to the single-neuron EEG contribution), and the soma membrane potential. These PSD transfer functions relate the PSDs of the respective measurements to the PSDs of the noisy input currents. With homogeneously distributed input currents across the neuronal membrane we find that all PSD transfer functions express asymptotic high-frequency power laws with power-law exponents analytically identified as for the soma membrane current, for the current-dipole moment, and for the soma membrane potential. Comparison with available data suggests that the apparent power laws observed in the high-frequency end of the PSD spectra may stem from uncorrelated current sources which are homogeneously distributed across the neural membranes and themselves exhibit pink () noise distributions. While the PSD noise spectra at low frequencies may be dominated by synaptic noise, our findings suggest that the high-frequency power laws may originate in noise from intrinsic ion channels. The significance of this finding goes beyond neuroscience as it demonstrates how power laws with a wide range of values for the power-law exponent α may arise from a simple, linear partial differential equation. PMID:25393030

  13. Using PARSEL Modules to Contextualizing the States-of-Matter Approach (SOMA) to Introductory Chemistry

    ERIC Educational Resources Information Center

    Tsaparlis, Georgios

    2008-01-01

    SOMA (States-Of-Matter Approach) is an introductory chemistry program for all students in the tenth or eleventh grade (age 16-17), which introduces chemistry through the separate study of the three states of matter. SOMA is basically a formalistic approach. In this paper, we discuss the use of PARSEL modules in providing a teaching approach to…

  14. Power laws from linear neuronal cable theory: power spectral densities of the soma potential, soma membrane current and single-neuron contribution to the EEG.

    PubMed

    Pettersen, Klas H; Lindén, Henrik; Tetzlaff, Tom; Einevoll, Gaute T

    2014-11-01

    Power laws, that is, power spectral densities (PSDs) exhibiting 1/f(α) behavior for large frequencies f, have been observed both in microscopic (neural membrane potentials and currents) and macroscopic (electroencephalography; EEG) recordings. While complex network behavior has been suggested to be at the root of this phenomenon, we here demonstrate a possible origin of such power laws in the biophysical properties of single neurons described by the standard cable equation. Taking advantage of the analytical tractability of the so called ball and stick neuron model, we derive general expressions for the PSD transfer functions for a set of measures of neuronal activity: the soma membrane current, the current-dipole moment (corresponding to the single-neuron EEG contribution), and the soma membrane potential. These PSD transfer functions relate the PSDs of the respective measurements to the PSDs of the noisy input currents. With homogeneously distributed input currents across the neuronal membrane we find that all PSD transfer functions express asymptotic high-frequency 1/f(α) power laws with power-law exponents analytically identified as α∞(I) = 1/2 for the soma membrane current, α∞(p) = 3/2 for the current-dipole moment, and α∞(V) = 2 for the soma membrane potential. Comparison with available data suggests that the apparent power laws observed in the high-frequency end of the PSD spectra may stem from uncorrelated current sources which are homogeneously distributed across the neural membranes and themselves exhibit pink (1/f) noise distributions. While the PSD noise spectra at low frequencies may be dominated by synaptic noise, our findings suggest that the high-frequency power laws may originate in noise from intrinsic ion channels. The significance of this finding goes beyond neuroscience as it demonstrates how 1/f(α) power laws with a wide range of values for the power-law exponent α may arise from a simple, linear partial differential equation.

  15. Neocortical Maturation during Adolescence: Change in Neuronal Soma Dimension

    ERIC Educational Resources Information Center

    Rabinowicz, Theodore; Petetot, Jean MacDonald-Comber; Khoury, Jane C.; de Courten-Myers, Gabrielle M.

    2009-01-01

    During adolescence, cognitive abilities increase robustly. To search for possible related structural alterations of the cerebral cortex, we measured neuronal soma dimension (NSD = width times height), cortical thickness and neuronal densities in different types of neocortex in post-mortem brains of five 12-16 and five 17-24 year-olds (each 2F,…

  16. Selfish genetic elements favor the evolution of a distinction between soma and germline.

    PubMed

    Johnson, Louise J

    2008-08-01

    Many multicellular organisms have evolved a dedicated germline. This can benefit the whole organism, but its advantages to genetic parasites have not been explored. Here I model the evolutionary success of a selfish element, such as a transposable element or endosymbiont, which is capable of creating or strengthening a germline-soma distinction in a primitively multicellular host, and find that it will always benefit the element to do so. Genes causing germline sequestration can therefore spread in a population even if germline sequestration is maladaptive for the host organism. Costly selfish elements are expected to survive only in sexual populations, so sexual species may experience an additional push toward germline-soma distinction, and hence toward cell differentiation and multicellularity.

  17. Psychosomatic symptoms as biomarkers: transcending the psyche-soma dichotomy.

    PubMed

    Neuman, Yair

    2010-01-01

    Following the advancement in understanding dynamical systems, the author presents a novel metaphor of psychosomatic symptoms as low-dimensional biomarkers. This metaphor, which transcends the old binary of psyche-soma, resonates with classical psychoanalytic concepts and with Matte-Blanco's idea of repetition as indicative of dimensionality reduction. The relevance of this metaphor for explanation, diagnosis, and treatment is illustrated through a case study of a male patient suffering from hyperprolactinemia.

  18. A brief account of the fractions of soma.

    PubMed

    Mahdihassan, S

    1990-04-01

    Soma was originally Sauma as the Sanskrit form of the Avesta name Haoma. It is a loan word from the Chinese term, Hao-Ma, fire coloured hempior fibrous items like hemp and also coloured yellow with a tinge of brown. The Aryans as hunters took its juice as anti-fatigue drink. It was extolled as panacea and even as drink of longevity. The plant and its stalks were crushed between stones to produce juice. There arose different fractions and these have been given in a regular chart here.

  19. A BRIEF ACCOUNT OF THE FRACTIONS OF SOMA

    PubMed Central

    Mahdihassan, S.

    1990-01-01

    Soma was originally Sauma as the Sanskrit form of the Avesta name Haoma. It is a loan word from the Chinese term, Hao-Ma, fire coloured hempior fibrous items like hemp and also coloured yellow with a tinge of brown. The Aryans as hunters took its juice as anti-fatigue drink. It was extolled as panacea and even as drink of longevity. The plant and its stalks were crushed between stones to produce juice. There arose different fractions and these have been given in a regular chart here. PMID:22557699

  20. Self Organized Multi Agent Swarms (SOMAS) for Network Security Control

    DTIC Science & Technology

    2009-03-01

    Normal hierarchy vs entangled hierarchy 2.5.7 Quantifying Entangledness . While self organization means that the swarm develops a consistent structure of...flexibility due to centralization of control and com- munication. Thus, self organized, entangled hierarchy multi-agent swarms are evolved in this study to...technique. The resulting design exhibits a self organized multi-agent swarm (SOMAS) with entangled hierarchical control and communication through the

  1. The indissociable unity of psyche and soma: a view from the Paris Psychosomatic School.

    PubMed

    Aisenstein, Marilia

    2006-06-01

    Depending on whether or not psyche/soma is seen as singular or dual, one may construct different systems explaining man and the world, life and death. In the author's view, the discoveries of psychoanalysis offer a perfectly cogent and unique solution to the famous mind/body problem. In transferring the duality psyche/soma on to the duality of drives, psychoanalysis places the origin of the thought process in the body. In Beyond the pleasure principle, Freud discusses the drastic effect of a painful somatic illness on the distribution and modalities of the libido. He provides a starting point for the Paris Psychosomatic School's psychoanalytical approach to patients afflicted with somatic illnesses. To illustrate the technical implications of this theory the author relates two clinical cases.

  2. Soma, food of the immortals according to the Bower Manuscript (Kashmir, 6th century A.D.).

    PubMed

    Leonti, Marco; Casu, Laura

    2014-08-08

    Food is medicine and vice versa. In Hindu and Ayurvedic medicine, and among human cultures of the Indian subcontinent in general, the perception of the food-medicine continuum is especially well established. The preparation of the exhilarating, gold-coloured Soma, Amrita or Ambrosia, the elixir and food of the 'immortals'-the Hindu pantheon-by the ancient Indo-Aryans, is described in the Rigveda in poetic hymns. Different theories regarding the botanical identity of Soma circulate, but no pharmacologically and historically convincing theory exists to date. We intend to contribute to the botanical, chemical and pharmacological characterisation of Soma through an analysis of two historical Amrita recipes recorded in the Bower Manuscript. The recipes are referred therein as panaceas (clarified butter) and also as a medicine to treat nervous diseases (oil), while no exhilarating properties are mentioned. Notwithstanding this, we hypothesise, that these recipes are related to the ca. 1800 years older Rigvedic Soma. We suppose that the psychoactive Soma ingredient(s) are among the components, possibly in smaller proportions, of the Amrita recipes preserved in the Bower Manuscript. The Bower Manuscript is a medical treatise recorded in the 6th century A.D. in Sanskrit on birch bark leaves, probably by Buddhist monks, and unearthed towards the end of the 19th century in Chinese Turkestan. We analysed two Amrita recipes from the Bower Manuscript, which was translated by Rudolf Hoernle into English during the early 20th century. A database search with the updated Latin binomials of the herbal ingredients was used to gather quantitative phytochemical and pharmacological information. Together, both Amrita recipes contain around 100 herbal ingredients. Psychoactive alkaloid containing species still important in Ayurvedic, Chinese and Thai medicine and mentioned in the recipe for 'Amrita-Prâsa clarified butter' and 'Amrita Oil' are: Tinospora cordifolia (Amrita, Guduchi), three

  3. Psyche and soma: New insights into the connection.

    PubMed

    Kumar, Rahul; Yeragani, Vikram K

    2010-01-01

    The interaction of Psyche and Soma are well known and this interaction happens through a complex network of feedback, medication, and modulation among the central and autonomic nervous systems, the endocrine system, the immune system, and the stress system. These systems, which were previously considered pristinely independent, in fact, interact at myriad levels. Psychoneuroimmunology (PNI) is an emerging discipline that focuses on various interactions among these body systems and provides the underpinnings of a scientific explanation for what is commonly referred to as the mind-body connection. This article reviews the relevant literature with an emphasis on Indian research.

  4. Psyche and soma: New insights into the connection

    PubMed Central

    Kumar, Rahul; Yeragani, Vikram K.

    2010-01-01

    The interaction of Psyche and Soma are well known and this interaction happens through a complex network of feedback, medication, and modulation among the central and autonomic nervous systems, the endocrine system, the immune system, and the stress system. These systems, which were previously considered pristinely independent, in fact, interact at myriad levels. Psychoneuroimmunology (PNI) is an emerging discipline that focuses on various interactions among these body systems and provides the underpinnings of a scientific explanation for what is commonly referred to as the mind-body connection. This article reviews the relevant literature with an emphasis on Indian research. PMID:21836684

  5. A soma-to-germline transformation in long-lived C. elegans mutants

    PubMed Central

    Curran, Sean P.; Wu, Xiaoyun; Riedel, Christian G.; Ruvkun, Gary

    2009-01-01

    Unlike the soma which ages during the lifespan of multicellular organisms, the germline traces an essentially immortal lineage. Genomic instability in somatic cells increases with age, and this decline in somatic maintenance might be regulated to facilitate resource reallocation toward reproduction at the expense of cellular senescence. We report here that C. elegans mutants with increased longevity exhibit a soma-to-germline transformation of gene expression programs normally limited to the germline. Decreased insulin-like signaling causes the somatic misexpression of germline-limited pie-1 and pgl family of genes in intestinal and ectodermal tissues. DAF-16/FoxO, the major transcriptional effector of insulin-like signaling, regulates pie-1 expression by directly binding to the pie-1 promoter. The somatic tissues of insulin-like mutants are more germline-like and protected from genotoxic stress. Gene inactivation of components of the cytosolic chaperonin complex that induce increased longevity also cause somatic misexpression of PGL-1. These results suggest that the acquisition of germline characteristics by the somatic cells of C. elegans mutants with increased longevity contributes to their increased health and survival. PMID:19506556

  6. Heterogeneous Intracellular Trafficking Dynamics of Brain-Derived Neurotrophic Factor Complexes in the Neuronal Soma Revealed by Single Quantum Dot Tracking

    PubMed Central

    Vermehren-Schmaedick, Anke; Krueger, Wesley; Jacob, Thomas; Ramunno-Johnson, Damien; Balkowiec, Agnieszka; Lidke, Keith A.; Vu, Tania Q.

    2014-01-01

    Accumulating evidence underscores the importance of ligand-receptor dynamics in shaping cellular signaling. In the nervous system, growth factor-activated Trk receptor trafficking serves to convey biochemical signaling that underlies fundamental neural functions. Focus has been placed on axonal trafficking but little is known about growth factor-activated Trk dynamics in the neuronal soma, particularly at the molecular scale, due in large part to technical hurdles in observing individual growth factor-Trk complexes for long periods of time inside live cells. Quantum dots (QDs) are intensely fluorescent nanoparticles that have been used to study the dynamics of ligand-receptor complexes at the plasma membrane but the value of QDs for investigating ligand-receptor intracellular dynamics has not been well exploited. The current study establishes that QD conjugated brain-derived neurotrophic factor (QD-BDNF) binds to TrkB receptors with high specificity, activates TrkB downstream signaling, and allows single QD tracking capability for long recording durations deep within the soma of live neurons. QD-BDNF complexes undergo internalization, recycling, and intracellular trafficking in the neuronal soma. These trafficking events exhibit little time-synchrony and diverse heterogeneity in underlying dynamics that include phases of sustained rapid motor transport without pause as well as immobility of surprisingly long-lasting duration (several minutes). Moreover, the trajectories formed by dynamic individual BDNF complexes show no apparent end destination; BDNF complexes can be found meandering over long distances of several microns throughout the expanse of the neuronal soma in a circuitous fashion. The complex, heterogeneous nature of neuronal soma trafficking dynamics contrasts the reported linear nature of axonal transport data and calls for models that surpass our generally limited notions of nuclear-directed transport in the soma. QD-ligand probes are poised to provide

  7. Amplitude Normalization of Dendritic EPSPs at the Soma of Binaural Coincidence Detector Neurons of the Medial Superior Olive.

    PubMed

    Winters, Bradley D; Jin, Shan-Xue; Ledford, Kenneth R; Golding, Nace L

    2017-03-22

    The principal neurons of the medial superior olive (MSO) encode cues for horizontal sound localization through comparisons of the relative timing of EPSPs. To understand how the timing and amplitude of EPSPs are maintained during propagation in the dendrites, we made dendritic and somatic whole-cell recordings from MSO principal neurons in brain slices from Mongolian gerbils. In somatic recordings, EPSP amplitudes were largely uniform following minimal stimulation of excitatory synapses at visualized locations along the dendrites. Similar results were obtained when excitatory synaptic transmission was eliminated in a low calcium solution and then restored at specific dendritic sites by pairing input stimulation and focal application of a higher calcium solution. We performed dual dendritic and somatic whole-cell recordings to measure spontaneous EPSPs using a dual-channel template-matching algorithm to separate out those events initiated at or distal to the dendritic recording location. Local dendritic spontaneous EPSP amplitudes increased sharply in the dendrite with distance from the soma (length constant, 53.6 μm), but their attenuation during propagation resulted in a uniform amplitude of ∼0.2 mV at the soma. The amplitude gradient of dendritic EPSPs was also apparent in responses to injections of identical simulated excitatory synaptic currents in the dendrites. Compartmental models support the view that these results extensively reflect the influence of dendritic cable properties. With relatively few excitatory axons innervating MSO neurons, the normalization of dendritic EPSPs at the soma would increase the importance of input timing versus location during the processing of interaural time difference cues in vivo SIGNIFICANCE STATEMENT The neurons of the medial superior olive analyze cues for sound localization by detecting the coincidence of binaural excitatory synaptic inputs distributed along the dendrites. Previous studies have shown that dendritic

  8. Amplitude Normalization of Dendritic EPSPs at the Soma of Binaural Coincidence Detector Neurons of the Medial Superior Olive

    PubMed Central

    Winters, Bradley D.; Jin, Shan-Xue; Ledford, Kenneth R.

    2017-01-01

    The principal neurons of the medial superior olive (MSO) encode cues for horizontal sound localization through comparisons of the relative timing of EPSPs. To understand how the timing and amplitude of EPSPs are maintained during propagation in the dendrites, we made dendritic and somatic whole-cell recordings from MSO principal neurons in brain slices from Mongolian gerbils. In somatic recordings, EPSP amplitudes were largely uniform following minimal stimulation of excitatory synapses at visualized locations along the dendrites. Similar results were obtained when excitatory synaptic transmission was eliminated in a low calcium solution and then restored at specific dendritic sites by pairing input stimulation and focal application of a higher calcium solution. We performed dual dendritic and somatic whole-cell recordings to measure spontaneous EPSPs using a dual-channel template-matching algorithm to separate out those events initiated at or distal to the dendritic recording location. Local dendritic spontaneous EPSP amplitudes increased sharply in the dendrite with distance from the soma (length constant, 53.6 μm), but their attenuation during propagation resulted in a uniform amplitude of ∼0.2 mV at the soma. The amplitude gradient of dendritic EPSPs was also apparent in responses to injections of identical simulated excitatory synaptic currents in the dendrites. Compartmental models support the view that these results extensively reflect the influence of dendritic cable properties. With relatively few excitatory axons innervating MSO neurons, the normalization of dendritic EPSPs at the soma would increase the importance of input timing versus location during the processing of interaural time difference cues in vivo. SIGNIFICANCE STATEMENT The neurons of the medial superior olive analyze cues for sound localization by detecting the coincidence of binaural excitatory synaptic inputs distributed along the dendrites. Previous studies have shown that dendritic

  9. Mapping of neuron soma size as an effective approach to delineate differences between neural populations.

    PubMed

    Lingley, Alexander J; Bowdridge, Joshua C; Farivar, Reza; Duffy, Kevin R

    2018-04-30

    A single histological marker applied to a slice of tissue often reveals myriad cytoarchitectonic characteristics that can obscure differences between neuron populations targeted for study. Isolation and measurement of a single feature from the tissue is possible through a variety of approaches, however, visualizing the data numerically or through graphs alone can preclude being able to identify important features and effects that are not obvious from direct observation of the tissue. We demonstrate an efficient, effective, and robust approach to quantify and visualize cytoarchitectural features in histologically prepared brain sections. We demonstrate that this approach is able to reveal small differences between populations of neurons that might otherwise have gone undiscovered. We used stereological methods to record the cross-sectional soma area and in situ position of neurons within sections of the cat, monkey, and human visual system. The two-dimensional coordinate of every measured cell was used to produce a scatter plot that recapitulated the natural spatial distribution of cells, and each point in the plot was color-coded according to its respective soma area. The final graphic display was a multi-dimensional map of neuron soma size that revealed subtle differences across neuron aggregations, permitted delineation of regional boundaries, and identified small differences between populations of neurons modified by a period of sensory deprivation. This approach to collecting and displaying cytoarchitectonic data is simple, efficient, and provides a means of investigating small differences between neuron populations. Copyright © 2018. Published by Elsevier B.V.

  10. Nuclear PTEN deficiency causes microcephaly with decreased neuronal soma size and increased seizure susceptibility.

    PubMed

    Igarashi, Atsushi; Itoh, Kie; Yamada, Tatsuya; Adachi, Yoshihiro; Kato, Takashi; Murata, Daisuke; Sesaki, Hiromi; Iijima, Miho

    2018-06-15

    Defects in phosphatase and tensin homolog (PTEN) are associated with neurological disorders and tumors. PTEN functions at two primary intracellular locations: the plasma membrane and the nucleus. At the membrane, PTEN functions as a phosphatidylinositol (3,4,5)-trisphosphate phosphatase and suppresses PI 3-kinase signaling that drives cell growth and tumorigenesis. However, the in vivo function of nuclear PTEN is unclear. Here, using CRISPR/Cas9, we generated a mouse model in which PTEN levels in the nucleus are decreased. Nuclear PTEN-deficient mice were born with microcephaly and maintained a small brain during adulthood. The size of neuronal soma was significantly smaller in the cerebellum, cerebral cortex, and hippocampus. Also, these mice were prone to seizure. No changes in PI 3-kinase signaling were observed. By contrast, the size of other organs was unaffected. Therefore, nuclear PTEN is essential for the health of the brain by promoting the growth of neuronal soma size during development. © 2018 Igarashi et al.

  11. Succinate dehydrogenase activity and soma size of motoneurons innervating different portions of the rat tibialis anterior

    NASA Technical Reports Server (NTRS)

    Ishihara, A.; Roy, R. R.; Edgerton, V. R.

    1995-01-01

    The spatial distribution, soma size and oxidative enzyme activity of gamma and alpha motoneurons innervating muscle fibres in the deep (away from the surface of the muscle) and superficial (close to the surface of the muscle) portions of the tibialis anterior in normal rats were determined. The deep portion had a higher percentage of high oxidative fibres than the superficial portion of the muscle. Motoneurons were labelled by retrograde neuronal transport of fluorescent tracers: Fast Blue and Nuclear Yellow were injected into the deep portion and Nuclear Yellow into the superficial portion of the muscle. Therefore, motoneurons innervating the deep portion were identified by both a blue fluorescent cytoplasm and a golden-yellow fluorescent nucleus, while motoneurons innervating the superficial portion were identified by only a golden-yellow fluorescent nucleus. After staining for succinate dehydrogenase activity on the same section used for the identification of the motoneurons, soma size and succinate dehydrogenase activity of the motoneurons were measured. The gamma and alpha motoneurons innervating both the deep and superficial portions were located primarily at L4 and were intermingled within the same region of the dorsolateral portion of the ventral horn in the spinal cord. Mean soma size was similar for either gamma or alpha motoneurons in the two portions of the muscle. The alpha motoneurons innervating the superficial portion had a lower mean succinate dehydrogenase activity than those innervating the deep portion of the muscle. An inverse relationship between soma size and succinate dehydrogenase activity of alpha, but not gamma, motoneurons innervating both the deep and superficial portions was observed. Based on three-dimensional reconstructions within the spinal cord, there were no apparent differences in the spatial distribution of the motoneurons, either gamma or alpha, associated with the deep and superficial compartments of the muscle. The data

  12. Cellular resolution circuit mapping with temporal-focused excitation of soma-targeted channelrhodopsin

    PubMed Central

    Baker, Christopher A; Elyada, Yishai M; Parra, Andres; Bolton, M McLean

    2016-01-01

    We describe refinements in optogenetic methods for circuit mapping that enable measurements of functional synaptic connectivity with single-neuron resolution. By expanding a two-photon beam in the imaging plane using the temporal focusing method and restricting channelrhodopsin to the soma and proximal dendrites, we are able to reliably evoke action potentials in individual neurons, verify spike generation with GCaMP6s, and determine the presence or absence of synaptic connections with patch-clamp electrophysiological recording. DOI: http://dx.doi.org/10.7554/eLife.14193.001 PMID:27525487

  13. Transcriptional silencing of a transgene by RNAi in the soma of C. elegans.

    PubMed

    Grishok, Alla; Sinskey, Jina L; Sharp, Phillip A

    2005-03-15

    The silencing of transgene expression at the level of transcription in the soma of Caenorhabditis elegans through an RNAi-dependent pathway has not been previously characterized. Most gene silencing due to RNAi in C. elegans occurs at the post-transcriptional level. We observed transcriptional silencing when worms containing the elt-2::gfp/LacZ transgene were fed RNA produced from the commonly used L4440 vector. The transgene and the vector share plasmid backbone sequences. This transgene silencing depends on multiple RNAi pathway genes, including dcr-1, rde-1, rde-4, and rrf-1. Unlike post-transcriptional gene silencing in worms, elt-2::gfp/LacZ silencing is dependent on the PAZ-PIWI protein Alg-1 and on the HP1 homolog Hpl-2. The latter is a chromatin silencing factor, and expression of the transgene is inhibited at the level of intron-containing precursor mRNA. This inhibition is accompanied by a decrease in the acetylation of histones associated with the transgene. This transcriptional silencing in the soma can be distinguished from transgene silencing in the germline by its inability to be transmitted across generations and its dependence on the rde-1 gene. We therefore define this type of silencing as RNAi-induced Transcriptional Gene Silencing (RNAi-TGS). Additional chromatin-modifying components affecting RNAi-TGS were identified in a candidate RNAi screen.

  14. Influence of spaceflight on succinate dehydrogenase activity and soma size of rat ventral horn neurons

    NASA Technical Reports Server (NTRS)

    Ishihara, A.; Ohira, Y.; Roy, R. R.; Nagaoka, S.; Sekiguchi, C.; Hinds, W. E.; Edgerton, V. R.

    1996-01-01

    Succinate dehydrogenase (SDH) activities and soma cross-sectional areas (CSA) of neurons in the dorsolateral region of the ventral horn at the L5 segmental level of the spinal cord in the rat were determined after 14 days of spaceflight and after 9 days of recovery on earth. The results were compared to those in age-matched ground-based control rats. Spinal cords were quick-frozen, and the SDH activity and CSA of a sample of neurons with a visible nucleus were determined using a digitizer and a computer-assisted image analysis system. An inverse relationship between CSA and SDH activity of neurons was observed in all groups of rats. No change in mean CSA or mean SDH activity or in the size distribution of neurons was observed following spaceflight or recovery. However, there was a selective decrease in the SDH activity of neurons with soma CSA between 500 and 800 microns2 in the flight rats, and this effect persisted for at least 9 days following return to 1 g. It remains to be determined whether the selected population of motoneurons or the specific motor pools affected by spaceflight may be restricted to specific muscles.

  15. Spikelets in Pyramidal Neurons: Action Potentials Initiated in the Axon Initial Segment That Do Not Activate the Soma.

    PubMed

    Michalikova, Martina; Remme, Michiel W H; Kempter, Richard

    2017-01-01

    Spikelets are small spike-like depolarizations that can be measured in somatic intracellular recordings. Their origin in pyramidal neurons remains controversial. To explain spikelet generation, we propose a novel single-cell mechanism: somato-dendritic input generates action potentials at the axon initial segment that may fail to activate the soma and manifest as somatic spikelets. Using mathematical analysis and numerical simulations of compartmental neuron models, we identified four key factors controlling spikelet generation: (1) difference in firing threshold, (2) impedance mismatch, and (3) electrotonic separation between the soma and the axon initial segment, as well as (4) input amplitude. Because spikelets involve forward propagation of action potentials along the axon while they avoid full depolarization of the somato-dendritic compartments, we conjecture that this mode of operation saves energy and regulates dendritic plasticity while still allowing for a read-out of results of neuronal computations.

  16. Spike sorting based upon machine learning algorithms (SOMA).

    PubMed

    Horton, P M; Nicol, A U; Kendrick, K M; Feng, J F

    2007-02-15

    We have developed a spike sorting method, using a combination of various machine learning algorithms, to analyse electrophysiological data and automatically determine the number of sampled neurons from an individual electrode, and discriminate their activities. We discuss extensions to a standard unsupervised learning algorithm (Kohonen), as using a simple application of this technique would only identify a known number of clusters. Our extra techniques automatically identify the number of clusters within the dataset, and their sizes, thereby reducing the chance of misclassification. We also discuss a new pre-processing technique, which transforms the data into a higher dimensional feature space revealing separable clusters. Using principal component analysis (PCA) alone may not achieve this. Our new approach appends the features acquired using PCA with features describing the geometric shapes that constitute a spike waveform. To validate our new spike sorting approach, we have applied it to multi-electrode array datasets acquired from the rat olfactory bulb, and from the sheep infero-temporal cortex, and using simulated data. The SOMA sofware is available at http://www.sussex.ac.uk/Users/pmh20/spikes.

  17. SOMA: A Proposed Framework for Trend Mining in Large UK Diabetic Retinopathy Temporal Databases

    NASA Astrophysics Data System (ADS)

    Somaraki, Vassiliki; Harding, Simon; Broadbent, Deborah; Coenen, Frans

    In this paper, we present SOMA, a new trend mining framework; and Aretaeus, the associated trend mining algorithm. The proposed framework is able to detect different kinds of trends within longitudinal datasets. The prototype trends are defined mathematically so that they can be mapped onto the temporal patterns. Trends are defined and generated in terms of the frequency of occurrence of pattern changes over time. To evaluate the proposed framework the process was applied to a large collection of medical records, forming part of the diabetic retinopathy screening programme at the Royal Liverpool University Hospital.

  18. MTOR-driven quasi-programmed aging as a disposable soma theory

    PubMed Central

    2013-01-01

    If life were created by intelligent design, we would indeed age from accumulation of molecular damage. Repair is costly and limited by energetic resources, and we would allocate resources rationally. But, albeit elegant, this design is fictional. Instead, nature blindly selects for short-term benefits of robust developmental growth. “Quasi-programmed” by the blind watchmaker, aging is a wasteful and aimless continuation of developmental growth, driven by nutrient-sensing, growth-promoting signaling pathways such as MTOR (mechanistic target of rapamycin). A continuous post-developmental activity of such gerogenic pathways leads to hyperfunctions (aging), loss of homeostasis, age-related diseases, non-random organ damage and death. This model is consistent with a view that (1) soma is disposable, (2) aging and menopause are not programmed and (3) accumulation of random molecular damage is not a cause of aging as we know it. PMID:23708516

  19. Neocortical maturation during adolescence: change in neuronal soma dimension.

    PubMed

    Rabinowicz, Theodore; Petetot, Jean Macdonald-Comber; Khoury, Jane C; de Courten-Myers, Gabrielle M

    2009-03-01

    During adolescence, cognitive abilities increase robustly. To search for possible related structural alterations of the cerebral cortex, we measured neuronal soma dimension (NSD = width times height), cortical thickness and neuronal densities in different types of neocortex in post-mortem brains of five 12-16 and five 17-24 year-olds (each 2F, 3M). Using a generalized mixed model analysis, mean normalized NSD comparing the age groups shows layer-specific change for layer 2 (p < .0001) and age-related differences between categorized type of cortex: primary/primary association cortex (BA 1, 3, 4, and 44) shows a generalized increase; higher-order regions (BA 9, 21, 39, and 45) also show increase in layers 2 and 5 but decrease in layers 3, 4, and 6 while limbic/orbital cortex (BA 23, 24, and 47) undergoes minor decrease (BA 1, 3, 4, and 44 vs. BA 9, 21, 39, and 45: p = .036 and BA 1, 3, 4, and 44 vs. BA 23, 24, and 47: p = .004). These data imply the operation of cortical layer- and type-specific processes of growth and regression adding new evidence that the human brain matures during adolescence not only functionally but also structurally.

  20. IP3-gated channels and their occurrence relative to CNG channels in the soma and dendritic knob of rat olfactory receptor neurons.

    PubMed

    Kaur, R; Zhu, X O; Moorhouse, A J; Barry, P H

    2001-05-15

    Olfactory receptor neurons respond to odorants with G protein-mediated increases in the concentrations of cyclic adenosine 3',5'-monophosphate (cAMP) and/or inositol-1,4,5-trisphosphate (IP3). This study provides evidence that both second messengers can directly activate distinct ion channels in excised inside-out patches from the dendritic knob and soma membrane of rat olfactory receptor neurons (ORNs). The IP3-gated channels in the dendritic knob and soma membranes could be classified into two types, with conductances of 40 +/- 7 pS (n = 5) and 14 +/- 3 pS (n = 4), with the former having longer open dwell times. Estimated values of the densities of both channels from the same inside-out membrane patches were very much smaller for IP3-gated than for CNG channels. For example, in the dendritic knob membrane there were about 1000 CNG channels x microm(-2) compared to about 85 IP3-gated channels x microm(-2). Furthermore, only about 36% of the dendritic knob patches responded to IP3, whereas 83% of the same patches responded to cAMP. In the soma, both channel densities were lower, with the CNG channel density again being larger ( approximately 57 channels x microm(-2)) than that of the IP3-gated channels ( approximately 13 channels x microm(-2)), with again a much smaller fraction of patches responding to IP3 than to cAMP. These results were consistent with other evidence suggesting that the cAMP-pathway dominates the IP3 pathway in mammalian olfactory transduction.

  1. Myosin II Motors and F-Actin Dynamics Drive the Coordinated Movement of the Centrosome and Soma during CNS Glial-Guided Neuronal Migration

    DOE Office of Scientific and Technical Information (OSTI.GOV)

    Solecki, Dr. David; Trivedi, Dr. Niraj; Govek, Eve-Ellen

    2009-01-01

    Lamination of cortical regions of the vertebrate brain depends on glial-guided neuronal migration. The conserved polarity protein Par6{alpha} localizes to the centrosome and coordinates forward movement of the centrosome and soma in migrating neurons. The cytoskeletal components that produce this unique form of cell polarity and their relationship to polarity signaling cascades are unknown. We show that F-actin and Myosin II motors are enriched in the neuronal leading process and that Myosin II activity is necessary for leading process actin dynamics. Inhibition of Myosin II decreased the speed of centrosome and somal movement, whereas Myosin II activation increased coordinated movement.more » Ectopic expression or silencing of Par6{alpha} inhibited Myosin II motors by decreasing Myosin light-chain phosphorylation. These findings suggest leading-process Myosin II may function to 'pull' the centrosome and soma forward during glial-guided migration by a mechanism involving the conserved polarity protein Par6{alpha}.« less

  2. Morphological characterization of rat entorhinal neurons in vivo: soma-dendritic structure and axonal domains.

    PubMed

    Lingenhöhl, K; Finch, D M

    1991-01-01

    We used in vivo intracellular labeling with horseradish peroxidase in order to study the soma-dendritic morphology and axonal projections of rat entorhinal neurons. The cells responded to hippocampal stimulation with inhibitory postsynaptic potentials, and thus likely received direct or indirect hippocampal input. All cells (n = 24) showed extensive dendritic domains that extended in some cases for more than 1 mm. The dendrites of layer II neurons were largely restricted to layers I and II or layers I-III, while the dendrites of deeper cells could extend through all cortical layers. Computed 3D rotations showed that the basilar dendrites of deep pyramids extended roughly parallel to the cortical layering, and that they were mostly confined to the layer containing the soma and layers immediately adjacent. Total dendritic lengths averaged 9.8 mm +/- 3.8 (SD), and ranged from 5 mm to more than 18 mm. Axonal processes could be visualized in 21 cells. Most of these showed axonal branching within the entorhinal cortex, sometimes extensive. Efferent axonal domains were reconstructed in detail in 3 layer II stellate cells. All 3 projected axons across the subicular complex to the dentate gyrus. One of these cells showed an extensive net-like axonal domain that also projected to several other structures, including the hippocampus proper, subicular complex, and the amygdalo-piriform transition area. The axons of layer III and IV cells projected to the angular bundle, where they continued in a rostral direction. In contrast to the layer II, III and IV cells, no efferent axonal branches leaving the entorhinal cortex could be visualized in 5 layer V neurons. The data indicate that entorhinal neurons can integrate input from a considerable volume of entorhinal cortex by virtue of their extensive dendritic domains, and provide a further basis for specifying the layers in which cells receive synaptic input. The extensive axonal branching pattern seen in most of the cells would

  3. From psyche to soma? Changing accounts of antisocial personality disorders in the American Journal of Psychiatry.

    PubMed

    Pickersgill, Martyn

    2010-09-01

    The history of psychiatry is often portrayed through the metaphor of a pendulum, the profession swinging back and forth between a concern with psyche and soma. Recent work critiquing the pendulum metaphor, however, suggests that it does not account for the complexity of psychiatry. This article explores the metaphor through an analysis of the changing aetiological accounts of personality disorders associated with antisocial behaviour advanced in the American Journal of Psychiatry from 1950 onwards. It is argued that the social, scientific and economic factors which help shape overarching professional trends in psychiatry only partly structure personality disorder discourse. If the pendulum swings, therefore, not all psychiatrists move with it.

  4. Meta-analysis of expression of l(3)mbt tumor-associated germline genes supports the model that a soma-to-germline transition is a hallmark of human cancers.

    PubMed

    Feichtinger, Julia; Larcombe, Lee; McFarlane, Ramsay J

    2014-05-15

    Evidence is starting to emerge indicating that tumorigenesis in metazoans involves a soma-to-germline transition, which may contribute to the acquisition of neoplastic characteristics. Here, we have meta-analyzed gene expression profiles of the human orthologs of Drosophila melanogaster germline genes that are ectopically expressed in l(3)mbt brain tumors using gene expression datasets derived from a large cohort of human tumors. We find these germline genes, some of which drive oncogenesis in D. melanogaster, are similarly ectopically activated in a wide range of human cancers. Some of these genes normally have expression restricted to the germline, making them of particular clinical interest. Importantly, these analyses provide additional support to the emerging model that proposes a soma-to-germline transition is a general hallmark of a wide range of human tumors. This has implications for our understanding of human oncogenesis and the development of new therapeutic and biomarker targets with clinical potential. © 2013 The Authors. Published by Wiley Periodicals, Inc. on behalf of UICC.

  5. An aftermath analysis of the 2014 coal mine accident in Soma, Turkey: Use of risk performance indicators based on historical experience.

    PubMed

    Spada, Matteo; Burgherr, Peter

    2016-02-01

    On the 13th of May 2014 a fire related incident in the Soma coal mine in Turkey caused 301 fatalities and more than 80 injuries. This has been the largest coal mine accident in Turkey, and in the OECD country group, so far. This study investigated if such a disastrous event should be expected, in a statistical sense, based on historical observations. For this purpose, PSI's ENSAD database is used to extract accident data for the period 1970-2014. Four different cases are analyzed, i.e., OECD, OECD w/o Turkey, Turkey and USA. Analysis of temporal trends for annual numbers of accidents and fatalities indicated a non-significant decreasing tendency for OECD and OECD w/o Turkey and a significant one for USA, whereas for Turkey both measures showed an increase over time. The expectation analysis revealed clearly that an event with the consequences of the Soma accident is rather unlikely for OECD, OECD w/o Turkey and USA. In contrast, such a severe accident has a substantially higher expectation for Turkey, i.e. it cannot be considered an extremely rare event, based on historical experience. This indicates a need for improved safety measures and stricter regulations in the Turkish coal mining sector in order to get closer to the rest of OECD. Copyright © 2015 Elsevier Ltd. All rights reserved.

  6. MTOR-driven quasi-programmed aging as a disposable soma theory: blind watchmaker vs. intelligent designer.

    PubMed

    Blagosklonny, Mikhail V

    2013-06-15

    If life were created by intelligent design, we would indeed age from accumulation of molecular damage. Repair is costly and limited by energetic resources, and we would allocate resources rationally. But, albeit elegant, this design is fictional. Instead, nature blindly selects for short-term benefits of robust developmental growth. "Quasi-programmed" by the blind watchmaker, aging is a wasteful and aimless continuation of developmental growth, driven by nutrient-sensing, growth-promoting signaling pathways such as MTOR (mechanistic target of rapamycin). A continuous post-developmental activity of such gerogenic pathways leads to hyperfunctions (aging), loss of homeostasis, age-related diseases, non-random organ damage and death. This model is consistent with a view that (1) soma is disposable, (2) aging and menopause are not programmed and (3) accumulation of random molecular damage is not a cause of aging as we know it.

  7. Cell differentiation and germ-soma separation in Ediacaran animal embryo-like fossils

    NASA Astrophysics Data System (ADS)

    Chen, Lei; Xiao, Shuhai; Pang, Ke; Zhou, Chuanming; Yuan, Xunlai

    2014-12-01

    Phosphorites of the Ediacaran Doushantuo Formation (~600 million years old) yield spheroidal microfossils with a palintomic cell cleavage pattern. These fossils have been variously interpreted as sulphur-oxidizing bacteria, unicellular protists, mesomycetozoean-like holozoans, green algae akin to Volvox, and blastula embryos of early metazoans or bilaterian animals. However, their complete life cycle is unknown and it is uncertain whether they had a cellularly differentiated ontogenetic stage, making it difficult to test their various phylogenetic interpretations. Here we describe new spheroidal fossils from black phosphorites of the Doushantuo Formation that have been overlooked in previous studies. These fossils represent later developmental stages of previously published blastula-like fossils, and they show evidence for cell differentiation, germ-soma separation, and programmed cell death. Their complex multicellularity is inconsistent with a phylogenetic affinity with bacteria, unicellular protists, or mesomycetozoean-like holozoans. Available evidence also indicates that the Doushantuo fossils are unlikely crown-group animals or volvocine green algae. We conclude that an affinity with cellularly differentiated multicellular eukaryotes, including stem-group animals or algae, is likely but more data are needed to constrain further the exact phylogenetic affinity of the Doushantuo fossils.

  8. Cell differentiation and germ-soma separation in Ediacaran animal embryo-like fossils.

    PubMed

    Chen, Lei; Xiao, Shuhai; Pang, Ke; Zhou, Chuanming; Yuan, Xunlai

    2014-12-11

    Phosphorites of the Ediacaran Doushantuo Formation (∼600 million years old) yield spheroidal microfossils with a palintomic cell cleavage pattern. These fossils have been variously interpreted as sulphur-oxidizing bacteria, unicellular protists, mesomycetozoean-like holozoans, green algae akin to Volvox, and blastula embryos of early metazoans or bilaterian animals. However, their complete life cycle is unknown and it is uncertain whether they had a cellularly differentiated ontogenetic stage, making it difficult to test their various phylogenetic interpretations. Here we describe new spheroidal fossils from black phosphorites of the Doushantuo Formation that have been overlooked in previous studies. These fossils represent later developmental stages of previously published blastula-like fossils, and they show evidence for cell differentiation, germ-soma separation, and programmed cell death. Their complex multicellularity is inconsistent with a phylogenetic affinity with bacteria, unicellular protists, or mesomycetozoean-like holozoans. Available evidence also indicates that the Doushantuo fossils are unlikely crown-group animals or volvocine green algae. We conclude that an affinity with cellularly differentiated multicellular eukaryotes, including stem-group animals or algae, is likely but more data are needed to constrain further the exact phylogenetic affinity of the Doushantuo fossils.

  9. Two classes of gap junction channels mediate soma-germline interactions essential for germline proliferation and gametogenesis in Caenorhabditis elegans.

    PubMed

    Starich, Todd A; Hall, David H; Greenstein, David

    2014-11-01

    In all animals examined, somatic cells of the gonad control multiple biological processes essential for germline development. Gap junction channels, composed of connexins in vertebrates and innexins in invertebrates, permit direct intercellular communication between cells and frequently form between somatic gonadal cells and germ cells. Gap junctions comprise hexameric hemichannels in apposing cells that dock to form channels for the exchange of small molecules. Here we report essential roles for two classes of gap junction channels, composed of five innexin proteins, in supporting the proliferation of germline stem cells and gametogenesis in the nematode Caenorhabditis elegans. Transmission electron microscopy of freeze-fracture replicas and fluorescence microscopy show that gap junctions between somatic cells and germ cells are more extensive than previously appreciated and are found throughout the gonad. One class of gap junctions, composed of INX-8 and INX-9 in the soma and INX-14 and INX-21 in the germ line, is required for the proliferation and differentiation of germline stem cells. Genetic epistasis experiments establish a role for these gap junction channels in germline proliferation independent of the glp-1/Notch pathway. A second class of gap junctions, composed of somatic INX-8 and INX-9 and germline INX-14 and INX-22, is required for the negative regulation of oocyte meiotic maturation. Rescue of gap junction channel formation in the stem cell niche rescues germline proliferation and uncovers a later channel requirement for embryonic viability. This analysis reveals gap junctions as a central organizing feature of many soma-germline interactions in C. elegans. Copyright © 2014 by the Genetics Society of America.

  10. Measurements of neuron soma size and density in rat dorsal striatum, nucleus accumbens core and nucleus accumbens shell: differences between striatal region and brain hemisphere, but not sex.

    PubMed

    Meitzen, John; Pflepsen, Kelsey R; Stern, Christopher M; Meisel, Robert L; Mermelstein, Paul G

    2011-01-07

    Both hemispheric bias and sex differences exist in striatal-mediated behaviors and pathologies. The extent to which these dimorphisms can be attributed to an underlying neuroanatomical difference is unclear. We therefore quantified neuron soma size and density in the dorsal striatum (CPu) as well as the core (AcbC) and shell (AcbS) subregions of the nucleus accumbens to determine whether these anatomical measurements differ by region, hemisphere, or sex in adult Sprague-Dawley rats. Neuron soma size was larger in the CPu than the AcbC or AcbS. Neuron density was greatest in the AcbS, intermediate in the AcbC, and least dense in the CPu. CPu neuron density was greater in the left in comparison to the right hemisphere. No attribute was sexually dimorphic. These results provide the first evidence that hemispheric bias in the striatum and striatal-mediated behaviors can be attributed to a lateralization in neuronal density within the CPu. In contrast, sexual dimorphisms appear mediated by factors other than gross anatomical differences. Copyright © 2010 Elsevier Ireland Ltd. All rights reserved.

  11. Identification of gonadal soma-derived factor involvement in Monopterus albus (protogynous rice field eel) sex change.

    PubMed

    Zhu, Yefei; Wang, Chunlei; Chen, Xiaowu; Guan, Guijun

    2016-07-01

    We studied molecular events and potential mechanisms underlying the process of female-to-male sex transformation in the rice field eel (Monopterus albus), a protogynous hermaphrodite fish in which the gonad is initially a female ovary and transforms into male testes. We cloned and identified a novel gonadal soma derived factor (GSDF), which encodes a member of the transforming growth factor-beta superfamily. gsdf expression was measured in gonads of female, intersex and male with reverse transcription-PCR and gsdf's role in sex transformation was studied with qPCR, histological analysis and dual-color in situ hybridization assays and compared to other sex-related genes. gsdf was correlated to Sertoli cell differentiation, indicating involvement in testicular differentiation and sex transformation from female to male in this species. A unique expression pattern reveals a potential role of gsdf essential for the sex transformation of rice field eels.

  12. Leaching characteristics of fly ash from thermal power plants of Soma and Tuncbilek, Turkey.

    PubMed

    Baba, Alper; Kaya, Abidin

    2004-02-01

    Use of lignite in power generation has led to increasing environmental problems associated not only with gaseous emissions but also with the disposal of ash residues. In particular, use of low quality coal with high ash content results in huge quantities of fly ash to be disposed of. The main problem related to fly ash disposal is the heavy metal content of the residue. In this regard, experimental results of numerous studies indicate that toxic trace metals may leach when fly ash contacts water. In this study, fly ash samples obtained from thermal power plants, namely Soma and Tunçbilek, located at the west part of Turkey, were subjected to toxicity tests such as European Committee for standardization (CEN) and toxicity characteristic leaching (TCLP) procedures of the U.S. Environmental Protection Agency (U.S. EPA). The geochemical composition of the tested ash samples from the power plant show variations depending on the coal burned in the plants. Furthermore, the CEN and TCLP extraction results showed variations such that the ash samples were classified as 'toxic waste' based on TCLP result whereas they were classified as 'non-toxic' wastes based on CEN results, indicating test results are pH dependent.

  13. The SOFIA Massive (SOMA) Star Formation Survey. I. Overview and First Results

    DOE Office of Scientific and Technical Information (OSTI.GOV)

    De Buizer, James M.; Shuping, Ralph; Liu, Mengyao

    We present an overview and first results of the Stratospheric Observatory For Infrared Astronomy Massive (SOMA) Star Formation Survey, which is using the FORCAST instrument to image massive protostars from ∼10 to 40 μ m. These wavelengths trace thermal emission from warm dust, which in Core Accretion models mainly emerges from the inner regions of protostellar outflow cavities. Dust in dense core envelopes also imprints characteristic extinction patterns at these wavelengths, causing intensity peaks to shift along the outflow axis and profiles to become more symmetric at longer wavelengths. We present observational results for the first eight protostars in themore » survey, i.e., multiwavelength images, including some ancillary ground-based mid-infrared (MIR) observations and archival Spitzer and Herschel data. These images generally show extended MIR/FIR emission along directions consistent with those of known outflows and with shorter wavelength peak flux positions displaced from the protostar along the blueshifted, near-facing sides, thus confirming qualitative predictions of Core Accretion models. We then compile spectral energy distributions and use these to derive protostellar properties by fitting theoretical radiative transfer models. Zhang and Tan models, based on the Turbulent Core Model of McKee and Tan, imply the sources have protostellar masses m {sub *} ∼ 10–50 M {sub ⊙} accreting at ∼10{sup −4}–10{sup −3} M {sub ⊙} yr{sup −1} inside cores of initial masses M {sub c} ∼ 30–500 M {sub ⊙} embedded in clumps with mass surface densities Σ{sub cl} ∼ 0.1–3 g cm{sup −2}. Fitting the Robitaille et al. models typically leads to slightly higher protostellar masses, but with disk accretion rates ∼100× smaller. We discuss reasons for these differences and overall implications of these first survey results for massive star formation theories.« less

  14. Mutation of Gonadal soma-derived factor induces medaka XY gonads to undergo ovarian development.

    PubMed

    Imai, Takuto; Saino, Kentaro; Matsuda, Masaru

    2015-11-06

    Gonochoristic species have a bipotential gonad that develops into a testis or an ovary. In species whose sex is determined by a genetic factor, the expression of a sex-determining gene is the first cue that directs the development of a bipotential gonad. Subsequent expression of downstream genes induces the gonad to develop into a testis or an ovary. The TGF-ß family member Gonadal soma-derived factor (Gsdf) is thought to be an important gene for gonadal development in teleost fish, and it is expressed at higher levels in the testis than in the ovary from early to mature stages. However, there is little functional information about the gene. In this study, we targeted the Gsdf coding region in the medaka fish Oryzias latipes using transcription activator-like effector nucleases (TALENs) and studied the phenotypes of the Gsdf mutant medaka. Although normal and heterozygous XY gonads developed into a testis, all XY gonads with a homozygous mutation in Gsdf developed into an ovary at early developmental stages. However, two-thirds of Gsdf mutant XY gonads developed into testes in the adult stages. These results demonstrate that although a gonad can develop into a complete testis in the absence of Gsdf, Gsdf function is critical for directing the bipotential gonad at early developmental stages. Therefore, Gsdf is an endogenous inducer of testicular development similar to a master sex-determining gene. Copyright © 2015 Elsevier Inc. All rights reserved.

  15. Identification and temporal decrease of 137Cs and 134Cs in groundwater in Minami-Soma City following the accident at the Fukushima Dai-ichi nuclear power plant.

    PubMed

    Shizuma, Kiyoshi; Fujikawa, Yoko; Kurihara, Momo; Sakurai, Yushi

    2018-03-01

    The Fukushima Dai-ichi Nuclear Power Plant (FDNPP) accident on March 11, 2011, caused severe radioactive contamination in Fukushima Prefecture. In order to clarify the safety of drinking water, we have conducted radiocesium monitoring of public tap water and groundwater in Minami-Soma City, which is 10-40 km north of the nuclear power plant. The source of tap water for Minami-Soma City is groundwater, which is treated by rapid filtration before distribution in two of the three treatment plants. The tap water was collected from six stations during 2012-2016 and groundwater was collected from 11 stations with wells between 5 and 100 m deep during 2014-2016. Radiocesium contamination of groundwater has been considered unlikely in Japan because of the small vertical migration velocity of radiocesium in Japanese soil. However, radiocesium was detected in public tap water after 2012, and the maximum 137 Cs concentration of 292 mBq L -1 was observed in 2013. In all the well water, radiocesium was detected between 2014 and 2015, at concentrations similar to those observed in tap water in the same period. In tap water and groundwater, radiocesium was decreased to below the detection limit in 2016 except for four stations. Radiocesium concentration in shallow water reached a maximum between 2013 and 2015, 2-4 years after the FDNPP accident, and then decreased. The results are interpreted that dissolved 137 Cs migrated in the soil and reached aquifers of various depth. Copyright © 2017 Elsevier Ltd. All rights reserved.

  16. Characterization of gonadal soma-derived factor expression during sex change in the protogynous wrasse, Halichoeres trimaculatus.

    PubMed

    Horiguchi, Ryo; Nozu, Ryo; Hirai, Toshiaki; Kobayashi, Yasuhisa; Nagahama, Yoshitaka; Nakamura, Masaru

    2013-04-01

    Sex change in fishes provides a good experimental model for understanding the mechanisms and plasticity of sex determination and differentiation. The three-spot wrasse, Halichoeres trimaculatus is a protogynous hermaphrodite. During sex change from female to male, the ovary is replaced by the testis through the degeneration of oocytes and subsequent spermatogenesis. In the present study, we cloned a cDNA-encoding gonadal soma-derived factor (GSDF) from protogynous wrasse and examined its expression pattern in the sexually mature gonads and the sex-changing gonad induced experimentally by aromatase inhibition. Expression of gsdf was predominantly observed in the testis, and it was mainly localized to the supporting cells surrounding the spermatogonia. In the ovary, only slight expression of gsdf was observed in morphologically undifferentiated supporting cells in contact with oogonia. During sex change, strong expression of gsdf appeared first in the supporting cells surrounding the gonial germ cells before the onset of spermatogenesis. Thereafter, the expression of gsdf continually increased in the supporting cells surrounding the proliferating spermatogonia throughout the sex change. These results suggest that gsdf is involved in the proliferation of spermatogonia and subsequent spermatogenesis in both the testis and the gonad in the early stages of sex change. Copyright © 2013 Wiley Periodicals, Inc.

  17. An under-active or over-active internal world? An exploration of parallel dynamics within psyche and soma, and the difficulty of internal regulation, in patients with Chronic Fatigue Syndrome and Myalgic Encephalomyelitis.

    PubMed

    Driver, Christine

    2005-04-01

    This paper explores the dynamics brought into analytic work when there is a symmetric fusion between psyche and soma within the patient. It will consider how such a fusion may emerge from reverberations between physical constitution and a lack of maternal attunement, containment and reflective function. I will describe the work with a patient, Jane, who was diagnosed with Myalgic Encephalomyelitis (ME) during the course of her analysis. The dynamic of her physical symptoms within the analytic work, and the impact of her internal affects and internal 'objects' within the transference and countertransference, indicated a difficulty in finding an homeostatic balance resulting in overactivity and underactivity at both somatic and psychological levels. Using the clinical work with Jane this paper will also examine the interrelationship between mother-infant attachment, an inadequate internalized maternal reflective function, affect dysregulation, unconscious fusion, the lack of psyche-soma differentiation and the impact of the latter in relation to internal regulation systems, or lack of, in patients with Chronic Fatigue Syndrome (CFS) and Myalgic Encephalomyelitis (ME). I will draw on similar work carried out by Holland (1997), Simpson (1997) and Simpson et al. (1997). The paper will also employ the concept of the reflective function (Fonagy 2001; Knox 2003), and consider Matte-Blanco's (1999) concepts of generalization and unconscious symmetry in relation to the patient's internal world. I go on to consider how analysis provides a point outside the 'fusion' that can enable the 'deadlock' to be broken.

  18. Upregulation of N-type calcium channels in the soma of uninjured dorsal root ganglion neurons contributes to neuropathic pain by increasing neuronal excitability following peripheral nerve injury.

    PubMed

    Yang, Jie; Xie, Man-Xiu; Hu, Li; Wang, Xiao-Fang; Mai, Jie-Zhen; Li, Yong-Yong; Wu, Ning; Zhang, Cheng; Li, Jin; Pang, Rui-Ping; Liu, Xian-Guo

    2018-07-01

    N-type voltage-gated calcium (Cav2.2) channels are expressed in the central terminals of dorsal root ganglion (DRG) neurons, and are critical for neurotransmitter release. Cav2.2 channels are also expressed in the soma of DRG neurons, where their function remains largely unknown. Here, we showed that Cav2.2 was upregulated in the soma of uninjured L4 DRG neurons, but downregulated in those of injured L5 DRG neurons following L5 spinal nerve ligation (L5-SNL). Local application of specific Cav2.2 blockers (ω-conotoxin GVIA, 1-100 μM or ZC88, 10-1000 μM) onto L4 and 6 DRGs on the operated side, but not the contralateral side, dose-dependently reversed mechanical allodynia induced by L5-SNL. Patch clamp recordings revealed that both ω-conotoxin GVIA (1 μM) and ZC88 (10 μM) depressed hyperexcitability in L4 but not in L5 DRG neurons of L5-SNL rats. Consistent with this, knockdown of Cav2.2 in L4 DRG neurons with AAV-Cav2.2 shRNA substantially prevented L5-SNL-induced mechanical allodynia and hyperexcitability of L4 DRG neurons. Furthermore, in L5-SNL rats, interleukin-1 beta (IL-1β) and IL-10 were upregulated in L4 DRGs and L5 DRGs, respectively. Intrathecal injection of IL-1β induced mechanical allodynia and Cav2.2 upregulation in bilateral L4-6 DRGs of naïve rats, whereas injection of IL-10 substantially prevented mechanical allodynia and Cav2.2 upregulation in L4 DRGs in L5-SNL rats. Finally, in cultured DRG neurons, Cav2.2 was dose-dependently upregulated by IL-1β and downregulated by IL-10. These data indicate that the upregulation of Cav2.2 in uninjured DRG neurons via IL-1β over-production contributes to neuropathic pain by increasing neuronal excitability following peripheral nerve injury. Copyright © 2018 Elsevier Inc. All rights reserved.

  19. Sleep Overnight Monitoring for Apnea in Patients Hospitalized with Heart Failure (SOMA-HF Study)

    PubMed Central

    Sharma, Sunil; Mather, Paul J.; Chowdhury, Anindita; Gupta, Suchita; Mukhtar, Umer; Willes, Leslee; Whellan, David J.; Malhotra, Atul; Quan, Stuart F.

    2017-01-01

    Introduction: Sleep-disordered breathing (SDB) is highly prevalent in hospitalized patients with congestive heart failure (CHF) and the condition is diagnosed and treated in only a minority of these patients. Portable monitoring (PM) is a screening option, but due to costs and the expertise required, many hospitals may find it impractical to implement. We sought to test the utility of an alternative approach for screening hospitalized CHF patients for SDB, high-resolution pulse oximetry (HRPO). Methods: We conducted a prospective controlled trial of 125 consecutive patients admitted to the hospital with CHF. Simultaneous PM and HRPO for a single night was performed. All but one patient were monitored on breathing room air. The HRPO-derived ODI (oxygen desaturation index) was compared with PM-derived respiratory event index (REI) using both receiver operator characteristic (ROC) curve analysis and a Bland-Altman plot. Results: Of 105 consecutive CHF patients with analyzable data, 61 (58%) were males with mean age of 64.9 ± 15.1 years and mean body mass index of 30.3 ± 8.3 kg/m2. Of the 105 patients, 10 (9.5%) had predominantly central sleep apnea (central events > 50% of the total events), although central events were noted in 42 (40%) of the patients. The ROC analysis showed an area under the curve of 0.89 for REI > 5 events/h. The Bland-Altman plot showed acceptable agreement with 95% limits of agreement between −28.5 to 33.7 events/h and little bias. Conclusions: We conclude that high-resolution pulse oximetry is a simple and cost-effective screening tool for SDB in CHF patients admitted to the hospital. Such screening approaches may be valuable for large-scale implementation and for the optimal design of interventional trials. Citation: Sharma S, Mather PJ, Chowdhury A, Gupta S, Mukhtar U, Willes L, Whellan DJ, Malhotra A, Quan SF. Sleep overnight monitoring for apnea in patients hospitalized with heart failure (SOMA-HF Study). J Clin Sleep Med. 2017

  20. Using computer simulations to determine the limitations of dynamic clamp stimuli applied at the soma in mimicking distributed conductance sources.

    PubMed

    Lin, Risa J; Jaeger, Dieter

    2011-05-01

    In previous studies we used the technique of dynamic clamp to study how temporal modulation of inhibitory and excitatory inputs control the frequency and precise timing of spikes in neurons of the deep cerebellar nuclei (DCN). Although this technique is now widely used, it is limited to interpreting conductance inputs as being location independent; i.e., all inputs that are biologically distributed across the dendritic tree are applied to the soma. We used computer simulations of a morphologically realistic model of DCN neurons to compare the effects of purely somatic vs. distributed dendritic inputs in this cell type. We applied the same conductance stimuli used in our published experiments to the model. To simulate variability in neuronal responses to repeated stimuli, we added a somatic white current noise to reproduce subthreshold fluctuations in the membrane potential. We were able to replicate our dynamic clamp results with respect to spike rates and spike precision for different patterns of background synaptic activity. We found only minor differences in the spike pattern generation between focal or distributed input in this cell type even when strong inhibitory or excitatory bursts were applied. However, the location dependence of dynamic clamp stimuli is likely to be different for each cell type examined, and the simulation approach developed in the present study will allow a careful assessment of location dependence in all cell types.

  1. Two Classes of Gap Junction Channels Mediate Soma-Germline Interactions Essential for Germline Proliferation and Gametogenesis in Caenorhabditis elegans

    PubMed Central

    Starich, Todd A.; Hall, David H.; Greenstein, David

    2014-01-01

    In all animals examined, somatic cells of the gonad control multiple biological processes essential for germline development. Gap junction channels, composed of connexins in vertebrates and innexins in invertebrates, permit direct intercellular communication between cells and frequently form between somatic gonadal cells and germ cells. Gap junctions comprise hexameric hemichannels in apposing cells that dock to form channels for the exchange of small molecules. Here we report essential roles for two classes of gap junction channels, composed of five innexin proteins, in supporting the proliferation of germline stem cells and gametogenesis in the nematode Caenorhabditis elegans. Transmission electron microscopy of freeze-fracture replicas and fluorescence microscopy show that gap junctions between somatic cells and germ cells are more extensive than previously appreciated and are found throughout the gonad. One class of gap junctions, composed of INX-8 and INX-9 in the soma and INX-14 and INX-21 in the germ line, is required for the proliferation and differentiation of germline stem cells. Genetic epistasis experiments establish a role for these gap junction channels in germline proliferation independent of the glp-1/Notch pathway. A second class of gap junctions, composed of somatic INX-8 and INX-9 and germline INX-14 and INX-22, is required for the negative regulation of oocyte meiotic maturation. Rescue of gap junction channel formation in the stem cell niche rescues germline proliferation and uncovers a later channel requirement for embryonic viability. This analysis reveals gap junctions as a central organizing feature of many soma–germline interactions in C. elegans. PMID:25195067

  2. Individual external doses below the lowest reference level of 1 mSv per year five years after the 2011 Fukushima nuclear accident among all children in Soma City, Fukushima: A retrospective observational study.

    PubMed

    Tsubokura, Masaharu; Murakami, Michio; Nomura, Shuhei; Morita, Tomohiro; Nishikawa, Yoshitaka; Leppold, Claire; Kato, Shigeaki; Kami, Masahiro

    2017-01-01

    After the 2011 Fukushima Daiichi nuclear power plant accident, little information has been available on individual doses from external exposure among residents living in radioactively contaminated areas near the nuclear plant; in the present study we evaluated yearly changes in the doses from external exposure after the accident and the effects of decontamination on external exposure. This study considered all children less than 16 years of age in Soma City, Fukushima who participated in annual voluntary external exposure screening programs during the five years after the accident (n = 5,363). In total, 14,405 screening results were collected. The median participant age was eight years. The geometric mean levels of annual additional doses from external exposure attributable to the Fukushima accident, decreased each year: 0.60 mSv (range: not detectable (ND)-4.29 mSv), 0.37 mSv (range: ND-3.61 mSv), 0.22 mSv (range: ND-1.44 mSv), 0.20 mSv (range: ND-1.87 mSv), and 0.17 mSv (range: ND-0.85 mSv) in 2011, 2012, 2013, 2014, and 2015, respectively. The proportion of residents with annual additional doses from external exposure of more than 1 mSv dropped from 15.6% in 2011 to zero in 2015. Doses from external exposure decreased more rapidly than those estimated from only physical decay, even in areas without decontamination (which were halved in 395 days from November 15, 2011), presumably due to the weathering effects. While the ratios of geometric mean doses immediately after decontamination to before were slightly lower than those during the same time in areas without decontamination, annual additional doses reduced by decontamination were small (0.04-0.24 mSv in the year of immediately after decontamination was completed). The results of this study showed that the levels of external exposure among Soma residents less than 16 years of age decreased during the five years after the Fukushima Daiichi nuclear power plant accident. Decontamination had only limited and

  3. The Significance of Dewey's Aesthetics in Art Education in the Age of Globalization

    ERIC Educational Resources Information Center

    Nakamura, Kazuyo

    2009-01-01

    On the occasion of Dewey's sesquicentennial anniversary, Kazuyo Nakamura explores Dewey's aesthetics, which holds the plurality of art and culture in high regard. Nakamura develops a theoretical foundation for art education in the present age of globalization based on educational insights drawn from Dewey's aesthetics. The theme of this essay…

  4. Japan Report.

    DTIC Science & Technology

    1987-02-03

    of Keidanren’s U.S. Investment Mission, who is also vice chairman of the Industrial Bank of Japan; Mamoru Sakai, leader of the B Group of...Keidanren’s U.S. Investment Mission, who is also a director of the Japan Long-Term Credit Bank ; Masayoshi Tozaki, leader of the C Group of Keidanren’s U.S...Constitution. At the same time, Federal Reserve Bank Chairman Volcker has repeatedly stressed that maintaining the value of the dollar is essential. In

  5. Numerical study of breakwater failure due to tsunami-like undular bore impacts: The case of the port of Soma.

    NASA Astrophysics Data System (ADS)

    Martin-Medina, Manuel; Morichon, Denis; Abadie, Stephane; Le Roy, Sylvestre; Lemoine, Anne

    2017-04-01

    The Tohoku tsunami, that impacted the Japanese coast in 2011, caused great damages on many offshore vertical breakwaters ranging from the erosion of the rubble mound to the partial displacement or total collapse of caissons. The breakwater failure mechanisms were function of the tsunami wave types that vary along the Japanese coast according to the bathymetry features. The Iwate coast, characterized by deep water depths and steep slopes, was mainly impacted by tsunami overflow leading in particular to the failure of the world's deepest breakwater of Kamaishi. In the shallow waters of the Sendai bay, observations showed that breakwaters protecting harbor entrances were impacted by short waves train resembling to undular bore. This work aims to investigate this latter type of tsunami wave impacts that are less reported in the literature. We chose to focus on the highly damaged offshore breakwater of Soma, located in the south part of the Sendai bay. The hydrodynamics conditions during the tsunami impact are investigated using the VARANS Thetis code (Desombre et al., 2012), which allows to simulate both the free surface flow and the flow inside the rubble mound simulated by a porous medium. The model is forced at the offshore boundaries by the Funwave Boussinesq code that describes the transformation of the tsunami waves from the source to the generation of undular bores in shallow waters. The study includes the computation of forces acting on the caissons. We discuss the relevance of describing the hydrodynamics at the short wave scale to assess breakwater stability in the course of tsunami-like undular bore impact. References Desombre, J., Morichon, D., & Mory, M. (2012). SIMULTANEOUS SURFACE AND SUBSURFACE AIR AND WATER FLOWS MODELLING IN THE SWASH ZONE. Coastal Engineering Proceedings, 1(33), 56.

  6. Modeling of the non-isothermal crystallization kinetics of polyamide 6 composites during thermoforming

    NASA Astrophysics Data System (ADS)

    Kugele, Daniel; Dörr, Dominik; Wittemann, Florian; Hangs, Benjamin; Rausch, Julius; Kärger, Luise; Henning, Frank

    2017-10-01

    The combination of thermoforming processes of continuous-fiber reinforced thermoplastics and injection molding offers a high potential for cost-effective use in automobile mass production. During manufacturing, the thermoplastic laminates are initially heated up to a temperature above the melting point. This is followed by continuous cooling of the material during the forming process, which leads to crystallization under non-isothermal conditions. To account for phase change effects in thermoforming simulation, an accurate modeling of the crystallization kinetics is required. In this context, it is important to consider the wide range of cooling rates, which are observed during processing. Consequently, this paper deals with the experimental investigation of the crystallization at cooling rates varying from 0.16 K/s to 100 K/s using standard differential scanning calorimetry (DSC) and fast scanning calorimetry (Flash DSC). Two different modeling approaches (Nakamura model, modified Nakamura-Ziabicki model) for predicting crystallization kinetics are parameterized according to DSC measurements. It turns out that only the modified Nakamura-Ziabicki model is capable of predicting crystallization kinetics for all investigated cooling rates. Finally, the modified Nakamura-Ziabicki model is validated by cooling experiments using PA6-CF laminates with embedded temperature sensors. It is shown that the modified Nakamura-Ziabicki model predicts crystallization at non-isothermal conditions and varying cooling rates with a good accuracy. Thus, the study contributes to a deeper understanding of the non-isothermal crystallization and presents an overall method for modeling crystallization under process conditions.

  7. Neuronal somata and extrasomal compartments play distinct roles during synapse formation between Lymnaea neurons.

    PubMed

    Xu, Fenglian; Luk, Collin C; Wiersma-Meems, Ryanne; Baehre, Kelly; Herman, Cameron; Zaidi, Wali; Wong, Noelle; Syed, Naweed I

    2014-08-20

    Proper synapse formation is pivotal for all nervous system functions. However, the precise mechanisms remain elusive. Moreover, compared with the neuromuscular junction, steps regulating the synaptogenic program at central cholinergic synapses remain poorly defined. In this study, we identified different roles of neuronal compartments (somal vs extrasomal) in chemical and electrical synaptogenesis. Specifically, the electrically synapsed Lymnaea pedal dorsal A cluster neurons were used to study electrical synapses, whereas chemical synaptic partners, visceral dorsal 4 (presynaptic, cholinergic), and left pedal dorsal 1 (LPeD1; postsynaptic) were explored for chemical synapse formation. Neurons were cultured in a soma-soma or soma-axon configuration and synapses explored electrophysiologically. We provide the first direct evidence that electrical synapses develop in a soma-soma, but not soma-axon (removal of soma) configuration, indicating the requirement of gene transcription regulation in the somata of both synaptic partners. In addition, the soma-soma electrical coupling was contingent upon trophic factors present in Lymnaea brain-conditioned medium. Further, we demonstrate that chemical (cholinergic) synapses between soma-soma and soma-axon pairs were indistinguishable, with both exhibiting a high degree of contact site and target cell type specificity. We also provide direct evidence that presynaptic cell contact-mediated, clustering of postsynaptic cholinergic receptors at the synaptic site requires transmitter-receptor interaction, receptor internalization, and a protein kinase C-dependent lateral migration toward the contact site. This study provides novel insights into synaptogenesis between central neurons revealing both distinct and synergistic roles of cell-cell signaling and extrinsic trophic factors in executing the synaptogenic program. Copyright © 2014 the authors 0270-6474/14/3411304-12$15.00/0.

  8. Soma size and Cav1.3 channel expression in vulnerable and resistant motoneuron populations of the SOD1G93A mouse model of ALS

    PubMed Central

    Shoenfeld, Liza; Westenbroek, Ruth E.; Fisher, Erika; Quinlan, Katharina A.; Tysseling, Vicki M.; Powers, Randall K.; Heckman, Charles J.; Binder, Marc D.

    2014-01-01

    Abstract Although the loss of motoneurons is an undisputed feature of amyotrophic lateral sclerosis (ALS) in man and in its animal models (SOD1 mutant mice), how the disease affects the size and excitability of motoneurons prior to their degeneration is not well understood. This study was designed to test the hypothesis that motoneurons in mutant SOD1G93A mice exhibit an enlargement of soma size (i.e., cross‐sectional area) and an increase in Cav1.3 channel expression at postnatal day 30, well before the manifestation of physiological symptoms that typically occur at p90 (Chiu et al. 1995). We made measurements of spinal and hypoglossal motoneurons vulnerable to degeneration, as well as motoneurons in the oculomotor nucleus that are resistant to degeneration. Overall, we found that the somata of motoneurons in male SOD1G93A mutants were larger than those in wild‐type transgenic males. When females were included in the two groups, significance was lost. Expression levels of the Cav1.3 channels were not differentiated by genotype, sex, or any interaction of the two. These results raise the intriguing possibility of an interaction between male sex steroid hormones and the SOD1 mutation in the etiopathogenesis of ALS. PMID:25107988

  9. Individual external doses below the lowest reference level of 1 mSv per year five years after the 2011 Fukushima nuclear accident among all children in Soma City, Fukushima: A retrospective observational study

    PubMed Central

    Murakami, Michio; Nomura, Shuhei; Morita, Tomohiro; Nishikawa, Yoshitaka; Leppold, Claire; Kato, Shigeaki; Kami, Masahiro

    2017-01-01

    After the 2011 Fukushima Daiichi nuclear power plant accident, little information has been available on individual doses from external exposure among residents living in radioactively contaminated areas near the nuclear plant; in the present study we evaluated yearly changes in the doses from external exposure after the accident and the effects of decontamination on external exposure. This study considered all children less than 16 years of age in Soma City, Fukushima who participated in annual voluntary external exposure screening programs during the five years after the accident (n = 5,363). In total, 14,405 screening results were collected. The median participant age was eight years. The geometric mean levels of annual additional doses from external exposure attributable to the Fukushima accident, decreased each year: 0.60 mSv (range: not detectable (ND)–4.29 mSv), 0.37 mSv (range: ND–3.61 mSv), 0.22 mSv (range: ND–1.44 mSv), 0.20 mSv (range: ND–1.87 mSv), and 0.17 mSv (range: ND–0.85 mSv) in 2011, 2012, 2013, 2014, and 2015, respectively. The proportion of residents with annual additional doses from external exposure of more than 1 mSv dropped from 15.6% in 2011 to zero in 2015. Doses from external exposure decreased more rapidly than those estimated from only physical decay, even in areas without decontamination (which were halved in 395 days from November 15, 2011), presumably due to the weathering effects. While the ratios of geometric mean doses immediately after decontamination to before were slightly lower than those during the same time in areas without decontamination, annual additional doses reduced by decontamination were small (0.04–0.24 mSv in the year of immediately after decontamination was completed). The results of this study showed that the levels of external exposure among Soma residents less than 16 years of age decreased during the five years after the Fukushima Daiichi nuclear power plant accident. Decontamination had only

  10. Clinical Investigation Program Annual Progress Report

    DTIC Science & Technology

    1989-10-01

    Investigators: Linda K. Kullama, Ph.D., Dr. Kenneth T. Nakamura,MD; Dr. Venkataraman Balaraman, MD, Wayne M. Ichimura, Biomedical Engineer. Department/Section...Investigators: John R. Claybaugh, Ph.D.; Kenneth T. Nakamura, MD; Dr. Venkataraman Balaraman, M.D. Department/Section: Clinical Investigation/Physiology Key...Pigs and Rats Principal ’Investigator: Linda K. Kullama, Ph.D.; John R. Claybaugh, Ph.D. Associate Investigators: Dr. Venkataraman Balaraman, M.D.; Dr

  11. A New Regulatory Mechanism for Kv7.2 Protein During Neuropathy: Enhanced Transport from the Soma to Axonal Terminals of Injured Sensory Neurons.

    PubMed

    Cisneros, Elsa; Roza, Carolina; Jackson, Nieka; López-García, José Antonio

    2015-01-01

    Kv7.2 channel expression has been reported to decrease in dorsal root ganglia (DRG) following the induction of a peripheral neuropathy while other experiments show that Kv7.2 accumulates in peripheral neuromas. The mechanisms underlying these novel expression patterns are poorly understood. Here we use immunofluorescence methods to analyze Kv7.2 protein expression changes in sensory neurons following peripheral axotomy and the potential role of axonal transport. Results indicate that DRG neurons express Kv7.2 in ~16% of neurons and that this number decreases by about 65% after axotomy. Damaged neurons were identified in DRG by application of the tracer Fluoro-ruby at the site of injury during surgery. Reduction of Kv7.2 expression was particularly strong in damaged neurons although some loss was also found in putative uninjured neurons. In parallel to the decrease in the soma of axotomized sensory neurons, Kv7.2 accumulated at neuromatose fiber endings. Blockade of axonal transport with either vinblastine (VLB) or colchicine (COL) abolished Kv7.2 redistribution in neuropathic animals. Channel distribution rearrangements did not occur following induction of inflammation in the hind paw. Behavioral tests indicate that protein rearrangements within sensory afferents are essential to the development of allodynia under neuropathic conditions. These results suggest that axotomy enhances axonal transport in injured sensory neurons, leading to a decrease of somatic expression of Kv7.2 protein and a concomitant accumulation in damaged fiber endings. Localized changes in channel expression patterns under pathological conditions may create novel opportunities for Kv7.2 channel openers to act as analgesics.

  12. A New Regulatory Mechanism for Kv7.2 Protein During Neuropathy: Enhanced Transport from the Soma to Axonal Terminals of Injured Sensory Neurons

    PubMed Central

    Cisneros, Elsa; Roza, Carolina; Jackson, Nieka; López-García, José Antonio

    2015-01-01

    Kv7.2 channel expression has been reported to decrease in dorsal root ganglia (DRG) following the induction of a peripheral neuropathy while other experiments show that Kv7.2 accumulates in peripheral neuromas. The mechanisms underlying these novel expression patterns are poorly understood. Here we use immunofluorescence methods to analyze Kv7.2 protein expression changes in sensory neurons following peripheral axotomy and the potential role of axonal transport. Results indicate that DRG neurons express Kv7.2 in ~16% of neurons and that this number decreases by about 65% after axotomy. Damaged neurons were identified in DRG by application of the tracer Fluoro-ruby at the site of injury during surgery. Reduction of Kv7.2 expression was particularly strong in damaged neurons although some loss was also found in putative uninjured neurons. In parallel to the decrease in the soma of axotomized sensory neurons, Kv7.2 accumulated at neuromatose fiber endings. Blockade of axonal transport with either vinblastine (VLB) or colchicine (COL) abolished Kv7.2 redistribution in neuropathic animals. Channel distribution rearrangements did not occur following induction of inflammation in the hind paw. Behavioral tests indicate that protein rearrangements within sensory afferents are essential to the development of allodynia under neuropathic conditions. These results suggest that axotomy enhances axonal transport in injured sensory neurons, leading to a decrease of somatic expression of Kv7.2 protein and a concomitant accumulation in damaged fiber endings. Localized changes in channel expression patterns under pathological conditions may create novel opportunities for Kv7.2 channel openers to act as analgesics. PMID:26696829

  13. Applications of Tol2 Transposon-Mediated Gene Transfer for Stable Integration and Conditional Expression of Electroporated Genes in Chicken Embryos

    NASA Astrophysics Data System (ADS)

    Sato, Yuki; Takahashi, Yoshiko

    Because of the high accessibility to developing embryos, avian embryos (chicken and quail) have long been used as a good model animal to study embryogenesis in vertebrates, especially amniotes (reviewed in Wolpert, 2004). The techniques used for “classical” avian embryology included tissue transplantations, tissue ablations, and cell-labeling by vital dye. At the end of the last century, the in ovo electropora tion technique was developed by Nakamura and his colleagues, and this modern method opened a way to study the roles of developmental genes directly in living embryos (Funahashi et al., 1999) reviewed in (Nakamura et al., 2004; Yasuda et al., 2000; Yasugi and Nakamura, 2000). This powerful technique allows us to introduce genes (DNA, RNA, morpholino) into embryos in a tissue-specific way by targeting a restricted area of embryonic tissues. Thus, the electroporation technique using chickens has provided numerous novel insights into the understanding of early development in vertebrates, making the chicken a unique model animal.

  14. Poly(Lactic Acid) Filled with Cassava Starch-g-Soybean Oil Maleate

    PubMed Central

    Kiangkitiwan, Nopparut; Srikulkit, Kawee

    2013-01-01

    Poly(lactic acid), PLA, is a biodegradable polymer, but its applications are limited by its high cost and relatively poorer properties when compared to petroleum-based plastics. The addition of starch powder into PLA is one of the most promising efforts because starch is an abundant and cheap biopolymer. However, the challenge is the major problem associated with poor interfacial adhesion between the hydrophilic starch granules and the hydrophobic PLA, leading to poorer mechanical properties. In this paper, soybean oil maleate (SOMA) was synthesized by grafting soybean oil with various weight percents of maleic anhydride (MA) using dicumyl peroxide (DCP) as an initiator. Then, SOMA was employed for the surface modifying of cassava starch powder, resulting in SOMA-g-STARCH. The obtained SOMA-g-STARCH was mixed with PLA in various weight ratios using twin-screw extruder, resulting in PLA/SOMA-g-STARCH. Finally, the obtained PLA/SOMA-g-STARCH composites were prepared by a compression molding machines. The compatibility, thermal properties, morphology properties, and mechanical properties were characterized and evaluated. The results showed that the compatibility, surface appearance, and mechanical properties at 90 : 10 and 80 : 20 ratios of PLA/SOMA-g-STARCH were the best. PMID:24307883

  15. UNC-16 (JIP3) Acts Through Synapse-Assembly Proteins to Inhibit the Active Transport of Cell Soma Organelles to Caenorhabditis elegans Motor Neuron Axons

    PubMed Central

    Edwards, Stacey L.; Morrison, Logan M.; Yorks, Rosalina M.; Hoover, Christopher M.; Boominathan, Soorajnath; Miller, Kenneth G.

    2015-01-01

    The conserved protein UNC-16 (JIP3) inhibits the active transport of some cell soma organelles, such as lysosomes, early endosomes, and Golgi, to the synaptic region of axons. However, little is known about UNC-16’s organelle transport regulatory function, which is distinct from its Kinesin-1 adaptor function. We used an unc-16 suppressor screen in Caenorhabditis elegans to discover that UNC-16 acts through CDK-5 (Cdk5) and two conserved synapse assembly proteins: SAD-1 (SAD-A Kinase), and SYD-2 (Liprin-α). Genetic analysis of all combinations of double and triple mutants in unc-16(+) and unc-16(−) backgrounds showed that the three proteins (CDK-5, SAD-1, and SYD-2) are all part of the same organelle transport regulatory system, which we named the CSS system based on its founder proteins. Further genetic analysis revealed roles for SYD-1 (another synapse assembly protein) and STRADα (a SAD-1-interacting protein) in the CSS system. In an unc-16(−) background, loss of the CSS system improved the sluggish locomotion of unc-16 mutants, inhibited axonal lysosome accumulation, and led to the dynein-dependent accumulation of lysosomes in dendrites. Time-lapse imaging of lysosomes in CSS system mutants in unc-16(+) and unc-16(−) backgrounds revealed active transport defects consistent with the steady-state distributions of lysosomes. UNC-16 also uses the CSS system to regulate the distribution of early endosomes in neurons and, to a lesser extent, Golgi. The data reveal a new and unprecedented role for synapse assembly proteins, acting as part of the newly defined CSS system, in mediating UNC-16’s organelle transport regulatory function. PMID:26354976

  16. The Preliminary Study on Procurement Biliary Convergence from Donors with Complicated Bile Duct Variant in Emergency Right Lobe Living Donor Liver Transplantation.

    PubMed

    Ye, Sheng; Dong, Jia-Hong; Duan, Wei-Dong; Ji, Wen-Bing; Liang, Yu-Rong

    2017-03-01

    The incidence of biliary complications after living donor adult liver transplantation (LDALT) is still high due to the bile duct variation and necessity reconstruction of multiple small bile ducts. The current surgical management of the biliary variants is unsatisfactory. We evaluated the role of a new surgical approach in a complicated hilar bile duct variant (Nakamura type IV and Nakamura type II) under emergent right lobe LDALT for high model for end-stage liver disease score patients. The common hepatic duct (CHD) and the left hepatic duct (LHD) of the donor were transected in a right-graft including short common trunks with right posterior and anterior bile ducts, whereas the LHD of the donor was anastomosed to the CHD and the common trunks of a right-graft bile duct and the recipient CHD was end-to-end anastomosed. Ten of 13 grafts (Nakamura types II, III, and IV) had two or more biliary orifices after right graft lobectomy; seven patients had biliary complications (53.8%). Later, the surgical innovation was carried out in five donors with variant bile duct (four Nakamura type IV and one type II), and, consequently, no biliary or other complications were observed in donors and recipients during 47-53 months of follow-up; significant differences ( P  < 0.05) were found when two stages were compared. Our initial experience suggests that, in the urgent condition of LDALT when an alternative live donor was unavailable, a surgical innovation of cutting part of the CHD trunks including variant right hepatic ducts in a complicated donor bile duct variant may facilitate biliary reconstruction and reduce long-term biliary complications.

  17. Morphology, classification, and distribution of the projection neurons in the dorsal lateral geniculate nucleus of the rat.

    PubMed

    Ling, Changying; Hendrickson, Michael L; Kalil, Ronald E

    2012-01-01

    The morphology of confirmed projection neurons in the dorsal lateral geniculate nucleus (dLGN) of the rat was examined by filling these cells retrogradely with biotinylated dextran amine (BDA) injected into the visual cortex. BDA-labeled projection neurons varied widely in the shape and size of their cell somas, with mean cross-sectional areas ranging from 60-340 µm(2). Labeled projection neurons supported 7-55 dendrites that spanned up to 300 µm in length and formed dendritic arbors with cross-sectional areas of up to 7.0 × 10(4) µm(2). Primary dendrites emerged from cell somas in three broad patterns. In some dLGN projection neurons, primary dendrites arise from the cell soma at two poles spaced approximately 180° apart. In other projection neurons, dendrites emerge principally from one side of the cell soma, while in a third group of projection neurons primary dendrites emerge from the entire perimeter of the cell soma. Based on these three distinct patterns in the distribution of primary dendrites from cell somas, we have grouped dLGN projection neurons into three classes: bipolar cells, basket cells and radial cells, respectively. The appendages seen on dendrites also can be grouped into three classes according to differences in their structure. Short "tufted" appendages arise mainly from the distal branches of dendrites; "spine-like" appendages, fine stalks with ovoid heads, typically are seen along the middle segments of dendrites; and "grape-like" appendages, short stalks that terminate in a cluster of ovoid bulbs, appear most often along the proximal segments of secondary dendrites of neurons with medium or large cell somas. While morphologically diverse dLGN projection neurons are intermingled uniformly throughout the nucleus, the caudal pole of the dLGN contains more small projection neurons of all classes than the rostral pole.

  18. First columbellid species (Gastropoda: Buccinoidea) from deep-sea hydrothermal vents, discovered in Okinawa Trough, Japan.

    PubMed

    Chen, Chong; Watanabe, Hiromi Kayama; Araya, Juan Francisco

    2017-12-12

    The molluscan diversity of deep-sea chemosynthetic ecosystems in Japan has been in general well documented with about 80 described species, of which over half are gastropods (Sasaki et al. 2005; Fujikura et al. 2012; Sasaki et al. 2016). Recently, however, a number of novel hydrothermal vent sites were discovered in the area using multibeam echo-sounding (Nakamura et al. 2015), providing opportunities for new discoveries. As a part of ongoing studies documenting the biodiversity of such sites, we present the first record of Columbellidae from hydrothermal vents, with a new species recovered from Natsu and Aki sites, in the Iheya North hydrothermal field (for map and background on the vent field see Nakamura et al. 2015).

  19. Multicellularity makes somatic differentiation evolutionarily stable

    PubMed Central

    Wahl, Mary E.; Murray, Andrew W.

    2016-01-01

    Many multicellular organisms produce two cell lineages: germ cells, whose descendants produce the next generation, and somatic cells, which support, protect, and disperse the germ cells. This germ-soma demarcation has evolved independently in dozens of multicellular taxa but is absent in unicellular species. A common explanation holds that in these organisms, inefficient intercellular nutrient exchange compels the fitness cost of producing nonreproductive somatic cells to outweigh any potential benefits. We propose instead that the absence of unicellular, soma-producing populations reflects their susceptibility to invasion by nondifferentiating mutants that ultimately eradicate the soma-producing lineage. We argue that multicellularity can prevent the victory of such mutants by giving germ cells preferential access to the benefits conferred by somatic cells. The absence of natural unicellular, soma-producing species previously prevented these hypotheses from being directly tested in vivo: to overcome this obstacle, we engineered strains of the budding yeast Saccharomyces cerevisiae that differ only in the presence or absence of multicellularity and somatic differentiation, permitting direct comparisons between organisms with different lifestyles. Our strains implement the essential features of irreversible conversion from germ line to soma, reproductive division of labor, and clonal multicellularity while maintaining sufficient generality to permit broad extension of our conclusions. Our somatic cells can provide fitness benefits that exceed the reproductive costs of their production, even in unicellular strains. We find that nondifferentiating mutants overtake unicellular populations but are outcompeted by multicellular, soma-producing strains, suggesting that multicellularity confers evolutionary stability to somatic differentiation. PMID:27402737

  20. 78 FR 68856 - National Human Genome Research Institute; Notice of Closed Meeting

    Federal Register 2010, 2011, 2012, 2013, 2014

    2013-11-15

    ... DEPARTMENT OF HEALTH AND HUMAN SERVICES National Institutes of Health National Human Genome... Nakamura, Ph.D., Scientific Review Officer, Scientific Review Branch, National Human Genome Research...-402-0838. [[Page 68857

  1. Branch Input Resistance and Steady Attenuation for Input to One Branch of a Dendritic Neuron Model

    PubMed Central

    Rall, Wilfrid; Rinzel, John

    1973-01-01

    Mathematical solutions and numerical illustrations are presented for the steady-state distribution of membrane potential in an extensively branched neuron model, when steady electric current is injected into only one dendritic branch. Explicit expressions are obtained for input resistance at the branch input site and for voltage attenuation from the input site to the soma; expressions for AC steady-state input impedance and attenuation are also presented. The theoretical model assumes passive membrane properties and the equivalent cylinder constraint on branch diameters. Numerical examples illustrate how branch input resistance and steady attenuation depend upon the following: the number of dendritic trees, the orders of dendritic branching, the electrotonic length of the dendritic trees, the location of the dendritic input site, and the input resistance at the soma. The application to cat spinal motoneurons, and to other neuron types, is discussed. The effect of a large dendritic input resistance upon the amount of local membrane depolarization at the synaptic site, and upon the amount of depolarization reaching the soma, is illustrated and discussed; simple proportionality with input resistance does not hold, in general. Also, branch input resistance is shown to exceed the input resistance at the soma by an amount that is always less than the sum of core resistances along the path from the input site to the soma. PMID:4715583

  2. Upper stimulation threshold for retinal ganglion cell activation.

    PubMed

    Meng, Kevin; Fellner, Andreas; Rattay, Frank; Ghezzi, Diego; Meffin, Hamish; Ibbotson, Michael R; Kameneva, Tatiana

    2018-08-01

    The existence of an upper threshold in electrically stimulated retinal ganglion cells (RGCs) is of interest because of its relevance to the development of visual prosthetic devices, which are designed to restore partial sight to blind patients. The upper threshold is defined as the stimulation level above which no action potentials (direct spikes) can be elicited in electrically stimulated retina. We collected and analyzed in vitro recordings from rat RGCs in response to extracellular biphasic (anodic-cathodic) pulse stimulation of varying amplitudes and pulse durations. Such responses were also simulated using a multicompartment model. We identified the individual cell variability in response to stimulation and the phenomenon known as upper threshold in all but one of the recorded cells (n  =  20/21). We found that the latencies of spike responses relative to stimulus amplitude had a characteristic U-shape. In silico, we showed that the upper threshold phenomenon was observed only in the soma. For all tested biphasic pulse durations, electrode positions, and pulse amplitudes above lower threshold, a propagating action potential was observed in the distal axon. For amplitudes above the somatic upper threshold, the axonal action potential back-propagated in the direction of the soma, but the soma's low level of hyperpolarization prevented action potential generation in the soma itself. An upper threshold observed in the soma does not prevent spike conductance in the axon.

  3. Adaptability of the oxidative capacity of motoneurons

    NASA Technical Reports Server (NTRS)

    Chalmers, G. R.; Roy, R. R.; Edgerton, V. R.

    1992-01-01

    Previous studies have demonstrated that a chronic change in neuronal activation can produce a change in soma oxidative capacity, suggesting that: (i) these 2 variables are directly related in neurons and (ii) ion pumping is an important energy requiring activity of a neuron. Most of these studies, however, have focused on reduced activation levels of sensory systems. In the present study the effect of a chronic increase or decrease in motoneuronal activity on motoneuron oxidative capacity and soma size was studied. In addition, the effect of chronic axotomy was studied as an indicator of whether cytoplasmic volume may also be related to the oxidative capacity of motoneurons. A quantitative histochemical assay for succinate dehydrogenase activity was used as a measure of motoneuron oxidative capacity in experimental models in which chronic electromyography has been used to verify neuronal activity levels. Spinal transection reduced, and spinal isolation virtually eliminated lumbar motoneuron electrical activity. Functional overload of the plantaris by removal of its major synergists was used to chronically increase neural activity of the plantaris motor pool. No change in oxidative capacity or soma size resulted from either a chronic increase or decrease in neuronal activity level. These data indicate that the chronic modulation of ionic transport and neurotransmitter turnover associated with action potentials do not induce compensatory metabolic responses in the metabolic capacity of the soma of lumbar motoneurons. Soma oxidative capacity was reduced in the axotomized motoneurons, suggesting that a combination of axoplasmic transport, intracellular biosynthesis and perhaps neurotransmitter turnover represent the major energy demands on a motoneuron. While soma oxidative capacity may be closely related to neural activity in some neural systems, e.g. visual and auditory, lumbar motoneurons appear to be much less sensitive to modulations in chronic activity levels.

  4. Genetics Home Reference: Clouston syndrome

    MedlinePlus

    ... M, Nakamura M, Farooq M, Fujikawa H, Kibbi AG, Ito M, Dahdah M, Matta M, Diab H, ... qualified healthcare professional . About Selection Criteria for Links Data Files & API Site Map Subscribe Customer Support USA. ...

  5. Complementary theta resonance filtering by two spatially segregated mechanisms in CA1 hippocampal pyramidal neurons.

    PubMed

    Hu, Hua; Vervaeke, Koen; Graham, Lyle J; Storm, Johan F

    2009-11-18

    Synaptic input to a neuron may undergo various filtering steps, both locally and during transmission to the soma. Using simultaneous whole-cell recordings from soma and apical dendrites from rat CA1 hippocampal pyramidal cells, and biophysically detailed modeling, we found two complementary resonance (bandpass) filters of subthreshold voltage signals. Both filters favor signals in the theta (3-12 Hz) frequency range, but have opposite location, direction, and voltage dependencies: (1) dendritic H-resonance, caused by h/HCN-channels, filters signals propagating from soma to dendrite when the membrane potential is close to rest; and (2) somatic M-resonance, caused by M/Kv7/KCNQ and persistent Na(+) (NaP) channels, filters signals propagating from dendrite to soma when the membrane potential approaches spike threshold. Hippocampal pyramidal cells participate in theta network oscillations during behavior, and we suggest that that these dual, polarized theta resonance mechanisms may convey voltage-dependent tuning of theta-mediated neural coding in the entorhinal/hippocampal system during locomotion, spatial navigation, memory, and sleep.

  6. EPHEDRA, THE OLDEST MEDICINAL PLANT WITH THE HISTORY OF AN UNINTERRUPTED USE

    PubMed Central

    Mahdihassan, S.

    1987-01-01

    Ephedra was a source of anti-fatigue drink. In later period it became a drink of immortality and longevity. The use of Soma as the first drink of a newly born child is mentioned in Rigveda. The author identifies the Soma of Rigveda with the Ephedra and established its use in ancient Rome and also highlights here its continuity among Zorostrains. PMID:22557597

  7. How good is our genome?

    PubMed Central

    Weill, Jean-Claude; Radman, Miroslav

    2004-01-01

    Our genome has evolved to perpetuate itself through the maintenance of the species via an uninterrupted chain of reproductive somas. Accordingly, evolution is not concerned with diseases occurring after the soma's reproductive stage. Following Richard Dawkins, we would like to reassert that we indeed live as disposable somas, slaves of our germline genome, but could soon start rebelling against such slavery. Cancer and its relation to the TP53 gene may offer a paradigmatic example. The observation that the latency period in cancer can be prolonged in mice by increasing the number of TP53 genes in their genome, suggests that sooner or later we will have to address the question of heritable disease avoidance via the manipulation of the human germline. PMID:15065661

  8. Spiking computation and stochastic amplification in a neuron-like semiconductor microstructure

    DOE Office of Scientific and Technical Information (OSTI.GOV)

    Samardak, A. S.; Laboratory of Thin Film Technologies, Far Eastern Federal University, Vladivostok 690950; Nogaret, A.

    2011-05-15

    We have demonstrated the proof of principle of a semiconductor neuron, which has dendrites, axon, and a soma and computes information encoded in electrical pulses in the same way as biological neurons. Electrical impulses applied to dendrites diffuse along microwires to the soma. The soma is the active part of the neuron, which regenerates input pulses above a voltage threshold and transmits them into the axon. Our concept of neuron is a major step forward because its spatial structure controls the timing of pulses, which arrive at the soma. Dendrites and axon act as transmission delay lines, which modify themore » information, coded in the timing of pulses. We have finally shown that noise enhances the detection sensitivity of the neuron by helping the transmission of weak periodic signals. A maximum enhancement of signal transmission was observed at an optimum noise level known as stochastic resonance. The experimental results are in excellent agreement with simulations of the FitzHugh-Nagumo model. Our neuron is therefore extremely well suited to providing feedback on the various mathematical approximations of neurons and building functional networks.« less

  9. Solutions for transients in arbitrarily branching cables: III. Voltage clamp problems.

    PubMed

    Major, G

    1993-07-01

    Branched cable voltage recording and voltage clamp analytical solutions derived in two previous papers are used to explore practical issues concerning voltage clamp. Single exponentials can be fitted reasonably well to the decay phase of clamped synaptic currents, although they contain many underlying components. The effective time constant depends on the fit interval. The smoothing effects on synaptic clamp currents of dendritic cables and series resistance are explored with a single cylinder + soma model, for inputs with different time courses. "Soma" and "cable" charging currents cannot be separated easily when the soma is much smaller than the dendrites. Subtractive soma capacitance compensation and series resistance compensation are discussed. In a hippocampal CA1 pyramidal neurone model, voltage control at most dendritic sites is extremely poor. Parameter dependencies are illustrated. The effects of series resistance compound those of dendritic cables and depend on the "effective capacitance" of the cell. Plausible combinations of parameters can cause order-of-magnitude distortions to clamp current waveform measures of simulated Schaeffer collateral inputs. These voltage clamp problems are unlikely to be solved by the use of switch clamp methods.

  10. The effects of rational and irrational self-verbalizations on performance efficiency and levels of anxiety.

    PubMed

    Rosin, L; Nelson, W M

    1983-03-01

    Investigated the effects of rational vs. irrational belief systems (as measured by the Ellis Irrational Values Scale) and rational vs. irrational self-verbalizations on levels of anxiety and persistence on a performance task. Ss (N = 40) were instructed to assemble a virtually insolvable task call Soma. The variables of interest were how long each S would persist on this task and how much anxiety (as measured by the A-State portion of the State-Trait Anxiety Inventory) was aroused in working on this task. Following a baseline trial trying to solve Soma, Ss were assigned to either a rational or irrational self-talk condition and were led to believe that such self-talk would help in a second attempt to solve Soma. In line with cognitive models of psychology, it was found that rational self-talk Ss showed a significant decrease in levels of state anxiety compared to irrational self-talk Ss in attempting to solve Soma in the second trial. Contrary to cognitive models of psychology, scores obtained from the EIVS and the A-Trait portion of the STAI were not found to be related to persistence.

  11. Transient Response in a Dendritic Neuron Model for Current Injected at One Branch

    PubMed Central

    Rinzel, John; Rall, Wilfrid

    1974-01-01

    Mathematical expressions are obtained for the response function corresponding to an instantaneous pulse of current injected to a single dendritic branch in a branched dendritic neuron model. The theoretical model assumes passive membrane properties and the equivalent cylinder constraint on branch diameters. The response function when used in a convolution formula enables one to compute the voltage transient at any specified point in the dendritic tree for an arbitrary current injection at a given input location. A particular numerical example, for a brief current injection at a branch terminal, illustrates the attenuation and delay characteristics of the depolarization peak as it spreads throughout the neuron model. In contrast to the severe attenuation of voltage transients from branch input sites to the soma, the fraction of total input charge actually delivered to the soma and other trees is calculated to be about one-half. This fraction is independent of the input time course. Other numerical examples, which compare a branch terminal input site with a soma input site, demonstrate that, for a given transient current injection, the peak depolarization is not proportional to the input resistance at the injection site and, for a given synaptic conductance transient, the effective synaptic driving potential can be significantly reduced, resulting in less synaptic current flow and charge, for a branch input site. Also, for the synaptic case, the two inputs are compared on the basis of the excitatory post-synaptic potential (EPSP) seen at the soma and the total charge delivered to the soma. PMID:4424185

  12. Neurons from the adult human dentate nucleus: neural networks in the neuron classification.

    PubMed

    Grbatinić, Ivan; Marić, Dušica L; Milošević, Nebojša T

    2015-04-07

    Topological (central vs. border neuron type) and morphological classification of adult human dentate nucleus neurons according to their quantified histomorphological properties using neural networks on real and virtual neuron samples. In the real sample 53.1% and 14.1% of central and border neurons, respectively, are classified correctly with total of 32.8% of misclassified neurons. The most important result present 62.2% of misclassified neurons in border neurons group which is even greater than number of correctly classified neurons (37.8%) in that group, showing obvious failure of network to classify neurons correctly based on computational parameters used in our study. On the virtual sample 97.3% of misclassified neurons in border neurons group which is much greater than number of correctly classified neurons (2.7%) in that group, again confirms obvious failure of network to classify neurons correctly. Statistical analysis shows that there is no statistically significant difference in between central and border neurons for each measured parameter (p>0.05). Total of 96.74% neurons are morphologically classified correctly by neural networks and each one belongs to one of the four histomorphological types: (a) neurons with small soma and short dendrites, (b) neurons with small soma and long dendrites, (c) neuron with large soma and short dendrites, (d) neurons with large soma and long dendrites. Statistical analysis supports these results (p<0.05). Human dentate nucleus neurons can be classified in four neuron types according to their quantitative histomorphological properties. These neuron types consist of two neuron sets, small and large ones with respect to their perykarions with subtypes differing in dendrite length i.e. neurons with short vs. long dendrites. Besides confirmation of neuron classification on small and large ones, already shown in literature, we found two new subtypes i.e. neurons with small soma and long dendrites and with large soma and short

  13. 75 FR 19984 - National Human Genome Research Institute; Notice of Closed Meetings

    Federal Register 2010, 2011, 2012, 2013, 2014

    2010-04-16

    ... DEPARTMENT OF HEALTH AND HUMAN SERVICES National Institutes of Health National Human Genome..., National Human Genome Research Institute, National Institutes of Health, 5635 Fishers Lane, Suite 4075... Nakamura, PhD, Scientific Review Officer, Scientific Review Branch, National Human Genome Research...

  14. 77 FR 60706 - National Human Genome Research Institute; Notice of Closed Meeting

    Federal Register 2010, 2011, 2012, 2013, 2014

    2012-10-04

    ... DEPARTMENT OF HEALTH AND HUMAN SERVICES National Institutes of Health National Human Genome... unwarranted invasion of personal privacy. Name of Committee: National Human Genome Research Institute Special.... Nakamura, Ph.D., Scientific Review Officer, Scientific Review Branch, National Human Genome Research...

  15. Journal of Special Operations Medicine. Volume 5, Edition 3, Summer 2005

    DTIC Science & Technology

    2005-01-01

    bacteri- al inoculation of wounded animals prevented infec- tion for three days, but therapy delayed for six hours was ineffective.7 Antibacterial activity ...the case of shock, unconsciousness, or penetrating abdominal injury. 3. In an animal model, antibacterial activity can be overcome if...SOF units and our active editorial consultants. 2) SOMA members receive the JSOM as part of membership. Please note, if you are a SOMA member and

  16. Bright gamma-ray emission from TCP J04432130+4721280 (V392 Per) detected by Fermi-LAT

    NASA Astrophysics Data System (ADS)

    Li, Kwan-Lok; Chomiuk, Laura; Strader, Jay

    2018-05-01

    We report the Fermi-LAT detection of the optical transient TCP J04432130+4721280 (V392 Per), which was discovered by Yuji Nakamura on 2018-04-29.4740 (CBET #4515) and later identified as a Galactic nova by Wagner et al. (ATel #11588).

  17. LED firm rejects Nobel laureate's olive branch

    NASA Astrophysics Data System (ADS)

    Banks, Michael

    2014-12-01

    Nobel laureate Shuji Nakamura says that he is not going to try and improve relations with his former employer, which he sued in 2001 over his development of the blue light-emitting diode (LED), after receiving a snub from them last month.

  18. Annexin II Dependent Mechanism of Breast Cancer Progression

    DTIC Science & Technology

    2009-06-01

    Sashida, T., Yoshida, M., Miyashita, T., and Nakamura, A. Treatment of advanced ovarian cancer with fibrinolytic inhibitor ( tranexamic acid ). Acta Obstet...from Calbiochem, (La Jolla, CA). Lysine–Sepharose and ε-aminocaproic acid (ε-ACA) were procured from Sigma (St. Louis, MO). Chromatography and

  19. 75 FR 52538 - National Human Genome Research Institute; Notice of Closed Meeting

    Federal Register 2010, 2011, 2012, 2013, 2014

    2010-08-26

    ... DEPARTMENT OF HEALTH AND HUMAN SERVICES National Institutes of Health National Human Genome... unwarranted invasion of personal privacy. Name of Committee: National Human Genome Research Institute Special... Person: Ken D. Nakamura, PhD, Scientific Review Officer, Scientific Review Branch, National Human Genome...

  20. VizieR Online Data Catalog: Long-term core-collapse supernova simulations (Nakamura+, 2016)

    NASA Astrophysics Data System (ADS)

    Nakamura, K.; Horiuchi, S.; Tanaka, M.; Hayama, K.; Takiwaki, T.; Kotake, K.

    2017-11-01

    In Table 2, we compiled a list of nearby RSGs from the literature. RSGs associated with OB associations and other RSGs. Our final RSG list consists of 212 RSG candidates. To estimate the CCSN rate of each galaxy, we adopt a subset of the Karachentsev catalogue for which the star formation rate can be observationally estimated. The resulting CCSN rates are summarized in the final column of Table 3. (2 data files).

  1. Role of Estrogens in the Size of Neuronal Somata of Paravaginal Ganglia in Ovariectomized Rabbits

    PubMed Central

    Hernández-Aragón, Laura G.; García-Villamar, Verónica; Carrasco-Ruiz, María de los Ángeles; Nicolás-Toledo, Leticia; Ortega, Arturo; Cuevas-Romero, Estela; Martínez-Gómez, Margarita

    2017-01-01

    We aimed to determine the role of estrogens in modulating the size of neuronal somata of paravaginal ganglia. Rabbits were allocated into control (C), ovariectomized (OVX), and OVX treated with estradiol benzoate (OVX + EB) groups to evaluate the neuronal soma area; total serum estradiol (E2) and testosterone (T) levels; the percentage of immunoreactive (ir) neurons anti-aromatase, anti-estrogen receptor (ERα, ERβ) and anti-androgen receptor (AR); the intensity of the immunostaining anti-glial cell line-derived neurotrophic factor (GDNF) and the GDNF family receptor alpha type 1 (GFRα1); and the number of satellite glial cells (SGCs) per neuron. There was a decrease in the neuronal soma size for the OVX group, which was associated with low T, high percentages of aromatase-ir and neuritic AR-ir neurons, and a strong immunostaining anti-GDNF and anti-GFRα1. The decrease in the neuronal soma size was prevented by the EB treatment that increased the E2 without affecting the T levels. Moreover, there was a high percentage of neuritic AR-ir neurons, a strong GDNF immunostaining in the SGC, and an increase in the SGCs per neuron. Present findings show that estrogens modulate the soma size of neurons of the paravaginal ganglia, likely involving the participation of the SGC. PMID:28316975

  2. DOE Office of Scientific and Technical Information (OSTI.GOV)

    Bulut, Y.; Karayigit, A.I.

    The coal-bearing Soma basin is one of the most productive lacustrine coal basins of western Anatolia-Turkey. This study mainly focuses on petrography of the feed coals (FCs) in the Soma power plant. A total of 16 feed coal samples were systematically collected once a week over an eight-week period from both group boiler units, B1-4 with 660 MW and B5-6 with 330 MW capacity. The most abundant maceral group of FCs is huminite, in which texto-ulminite, eu-ulminite, attrinite, densinite are rich. Liptinite group macerals in FCs include mainly sporinite, resinite, and liptodetrinite, which are considerably higher than the other identifiedmore » liptinite macerals. In the inertinite group, fusinite and inertodetrinite are more abundant. Identifiable minerals with petrographical studies are pyrite, siderite, other minerals (e. g., carbonates, clay minerals, quartz, feldspar, etc.), and fossil shells. This study shows that FCs used are subbituminous in rank with mean random ulminite reflectance of 0.43% Rr oil from B1-4 units and 0.39% Rr oil from B5-6 units. This indicates that coal rank is slightly higher in the central mines (southern Soma) than in the Denis mines (northern Soma).« less

  3. A molluscan model system in the search for the engram.

    PubMed

    Lukowiak, Ken; Sangha, Susan; Scheibenstock, Andi; Parvez, Kashif; McComb, Chloe; Rosenegger, David; Varshney, Nishi; Sadamoto, Hisayo

    2003-01-01

    A 3-neuron central pattern generator, whose sufficiency and necessity has been directly demonstrated, mediates aerial respiratory behaviour in the pond snail, Lymnaea stagnalis. This behaviour can be operantly conditioned, and this associative learning is consolidated into long-lasting memory. Depending on the operant conditioning training procedure used the learning can be consolidated into intermediate term (ITM) or long-term memory (LTM). ITM persists for only 2-3 h, whilst LTM persists for days to weeks. LTM is dependent on both altered gene activity and new protein synthesis while ITM is only dependent on new protein synthesis. We have now directly established that one of the 3-CPG neurons, RPeD1, is a site of LTM formation and storage. We did this by ablating the soma of RPeD1 and leaving behind a functional primary neurite capable of mediating the necessary synaptic interactions to drive aerial respiratory behaviour by the 3-neuron CPG. However, following soma ablation the neuronal circuit is only capable of mediating learning and ITM. LTM can no longer be demonstrated. However, if RPeD1's soma is ablated after LTM consolidation memory is still present. Thus the soma is not needed for the retention of LTM. Using a similar strategy it may be possible to block forgetting.

  4. Changes in functional metabolism in the rat central nervous system following spaceflight

    NASA Technical Reports Server (NTRS)

    Murakami, D. M.; Miller, J. D.; Fuller, C. A.

    1985-01-01

    The neuronal metabolism and soma size of neurons within the paraventricular nucleus (PVN) and the supraoptic nucleus of rats are analyzed. Five male Sprague-Dawley rats were flown on Spacelab 3 for 7 days under a 12:12 light/dark cycle and unlimited food and water, and a control group was kept on the ground under similar conditions. The preparation of the hypothalamus of the rats for microscopic examination using thionin or the cytochrome oxidase (CYOX) technique is described. CYOX activity and soma size within the PVN are evaluated. The effects of water drinking pattern and space flight on CYOX activity and soma size are investigated. The data reveal that the flight rats with normal drinking patterns display a decrease in neuronal metabolism within the vasopressin-containing neurons of the hypothalamus and this metabolic change may reflect fluid shifts caused by microgravity.

  5. Regulation of Survival by IKKe in Inflammatory Breast Cancer Involves EpCAM

    DTIC Science & Technology

    2016-02-01

    responses and normalizes inflammatory cytokines in murine myeloproliferative neoplasms . Blood. 2010;115(25):5232-40. 29. Duncan JS, Whittle MC, Nakamura K...responses and normalizes inflammatory cytokines in murine myeloprolifer - ative neoplasms . Blood. 2010;115(25):5232–5240. 34. Aref AR, et al. Screening

  6. NextGen Avionics Roadmap Version 1.0

    DTIC Science & Technology

    2008-10-24

    monetized benefit streams when available. Since the source analyses had been conducted at different times using a range of operational and economic...Mrkoci BAE Systems Dave Nakamura Boeing Rob Pappas FAA Dharmesh Patel Honeywell Art Politano FAA Jean- Claude Richard Thales Avionics Brian E. Smith

  7. Journal of Special Operations Medicine, Volume 6, Edition 4

    DTIC Science & Technology

    2006-01-01

    units and our active editorial consultants. 2) SOMA members receive the JSOM as part of membership. Please note, if you are a SOMA member and are...directed by the Commander. As of September, the SOF Warrior, Program Executive Office (PEO) has an active and forward moving TC3 program that will...AFSOC medics have been actively deployed around the world. The 352nd Special Operations Group (SOG) medics support- ed a humanitarian non-combatant

  8. Journal of Special Operations Medicine, Volume 7, Edition 1

    DTIC Science & Technology

    2007-01-01

    SOMA through www.somaonline.org or contact MSG Russell Justice at justicer@earthlink.net. SOMA pro - vides a very valuable means of obtaining SOF...battlefield. The committee now has representation from all the Serv- ices and is busy deciding which way it needs to pro - ceed. There should be a...medical lessons learned and unit after actions reports (AARs) that con - tain combat mission needs has been a discussed item; this has been

  9. Untangling elevation-related differences in the hippocampus in food-caching mountain chickadees: the effect of a uniform captive environment.

    PubMed

    Freas, C A; Bingman, K; Ladage, L D; Pravosudov, V V

    2013-01-01

    Variation in environmental conditions associated with differential selection on spatial memory has been hypothesized to result in evolutionary changes in the morphology of the hippocampus, a brain region involved in spatial memory. At the same time, it is well known that the morphology of the hippocampus might also be directly affected by environmental conditions. Understanding the role of environment-based plasticity is therefore critical when investigating potential adaptive evolutionary changes in the hippocampus associated with environmental variation. We previously demonstrated large elevation-related variation in hippocampus morphology in mountain chickadees over an extremely small spatial scale. We hypothesized that this variation is related to differential selection pressures associated with differences in winter climate severity along an elevation gradient, which make different demands on spatial memory used for food cache retrieval. Here, we tested whether such variation is experience based, generated by potential differences in the environment, by comparing the hippocampus morphology of chickadees from different elevations maintained in a uniform captive environment in a laboratory with those sampled directly from the wild. In addition, we compared hippocampal neuron soma size in chickadees sampled directly from the wild with those maintained in laboratory conditions with restricted and unrestricted spatial memory use via manipulation of food-caching experiences to test whether memory use can affect neuron soma size. There were significant elevation-related differences in hippocampus volume and the total number of hippocampal neurons, but not in neuron soma size, in captive birds. Captive environmental conditions were associated with a large reduction in hippocampus volume and neuron soma size, but not in the total number of neurons or in neuron soma size in other telencephalic regions. Restriction of memory use while in laboratory conditions produced no

  10. Rewarding success

    NASA Astrophysics Data System (ADS)

    captainbonkers

    2015-01-01

    In reply to the news article "LED firm rejects Nobel laureate's olive branch" (December 2014 p7, http://ow.ly/EgLs7) about the long-running feud between Shuji Nakamura and his former employer, Nichia, over compensation for patents on efficient blue light-emitting diodes.

  11. Space-time wiring specificity supports direction selectivity in the retina

    PubMed Central

    Zlateski, Aleksandar; Lee, Kisuk; Richardson, Mark; Turaga, Srinivas C.; Purcaro, Michael; Balkam, Matthew; Robinson, Amy; Behabadi, Bardia F.; Campos, Michael; Denk, Winfried; Seung, H. Sebastian

    2014-01-01

    How does the mammalian retina detect motion? This classic problem in visual neuroscience has remained unsolved for 50 years. In search of clues, we reconstructed Off-type starburst amacrine cells (SACs) and bipolar cells (BCs) in serial electron microscopic images with help from EyeWire, an online community of “citizen neuroscientists.” Based on quantitative analyses of contact area and branch depth in the retina, we found evidence that one BC type prefers to wire with a SAC dendrite near the SAC soma, while another BC type prefers to wire far from the soma. The near type is known to lag the far type in time of visual response. A mathematical model shows how such “space-time wiring specificity” could endow SAC dendrites with receptive fields that are oriented in space-time and therefore respond selectively to stimuli that move in the outward direction from the soma. PMID:24805243

  12. Space-time wiring specificity supports direction selectivity in the retina.

    PubMed

    Kim, Jinseop S; Greene, Matthew J; Zlateski, Aleksandar; Lee, Kisuk; Richardson, Mark; Turaga, Srinivas C; Purcaro, Michael; Balkam, Matthew; Robinson, Amy; Behabadi, Bardia F; Campos, Michael; Denk, Winfried; Seung, H Sebastian

    2014-05-15

    How does the mammalian retina detect motion? This classic problem in visual neuroscience has remained unsolved for 50 years. In search of clues, here we reconstruct Off-type starburst amacrine cells (SACs) and bipolar cells (BCs) in serial electron microscopic images with help from EyeWire, an online community of 'citizen neuroscientists'. On the basis of quantitative analyses of contact area and branch depth in the retina, we find evidence that one BC type prefers to wire with a SAC dendrite near the SAC soma, whereas another BC type prefers to wire far from the soma. The near type is known to lag the far type in time of visual response. A mathematical model shows how such 'space-time wiring specificity' could endow SAC dendrites with receptive fields that are oriented in space-time and therefore respond selectively to stimuli that move in the outward direction from the soma.

  13. From synapse to nucleus and back again--communication over distance within neurons.

    PubMed

    Fainzilber, Mike; Budnik, Vivian; Segal, Rosalind A; Kreutz, Michael R

    2011-11-09

    How do neurons integrate intracellular communication from synapse to nucleus and back? Here we briefly summarize aspects of this topic covered by a symposium at Neuroscience 2011. A rich repertoire of signaling mechanisms link both dendritic terminals and axon tips with neuronal soma and nucleus, using motor-dependent transport machineries to traverse the long intracellular distances along neuronal processes. Activation mechanisms at terminals include localized translation of dendritic or axonal RNA, proteolytic cleavage of receptors or second messengers, and differential phosphorylation of signaling moieties. Signaling complexes may be transported in endosomes, or as non-endosomal complexes associated with importins and dynein. Anterograde transport of RNA granules from the soma to neuronal processes, coupled with retrograde transport of proteins translated locally at terminals or within processes, may fuel ongoing bidirectional communication between soma and synapse to modulate synaptic plasticity as well as neuronal growth and survival decisions.

  14. NMDAR-1 staining in the lateral geniculate nucleus of normal and visually deprived cats.

    PubMed

    Ziburkus, J; Bickford, M E; Guido, W

    2000-01-01

    In normal adult cats, a monoclonal antibody directed toward the NR-1 subunit of the N-methyl-D-aspartate (NMDA) receptor (Pharmingen, clone 54.1) produced dense cellular and neuropil labeling throughout all layers of the lateral geniculate nucleus (LGN) and adjacent thalamic nuclei, including the thalamic reticular, perigeniculate, medial intralaminar, and ventral lateral geniculate nuclei. Cellular staining revealed well-defined somata, and in some cases proximal dendrites. NMDAR-1 cell labeling was also evident in the LGN of early postnatal kittens, suggesting that developing LGN cells possess this receptor subunit at or before eye opening. Within the A-layers of the adult LGN, staining encompassed a wide range of soma sizes. Soma size comparisons of NMDAR-1 stained cells with those stained with an antibody directed toward a nonphosphorylated neurofilament protein (SMI-32), which selectively stains Y-relay cells (Bickford et al., 1998), or an antibody to glutamic acid decarboxylase (GAD), which stains for GABAergic interneurons, suggested that NMDA receptors are utilized by relay cells and interneurons. NMDAR-1 staining was also observed in the LGN of cats with early monocular lid suture. Although labeling was apparent in both deprived and nondeprived A-layers of LGN, the distribution of soma sizes was significantly different. In the deprived A-layers of LGN, staining was limited to small- and medium-sized cells. Cells with relatively large soma were lacking. However, cell density measurements as well as soma size comparisons with cells stained for Nissl substance suggested these differences were due to deprivation-induced cell shrinkage and not to a loss of NMDAR-1 staining in Y-cells. Taken together, these results suggest that NMDA receptors are utilized by both relay cells and interneurons in LGN and that alterations in early visual experience do not necessarily affect the expression of NMDA receptors in the LGN.

  15. [Psyche and soma--Descartes in our hearts?].

    PubMed

    Jørgensen, J

    1993-10-20

    The essay deals with the mind-body problem. The first part describes the different views held by philosophers from Plato up to modern times, stressing the standpoint of René Descartes for medical philosophy and dualism. The author outlines the new research field of psychoneuroimmunology, and asks whether this could be one of the keys to the mind-body problem. The concept of anomaly is discussed, taking placebo and nocebo as prominent examples. Finally the author outlines modern holistic thinking based on a general systems theory, with biology as a dynamic interplay of culture, ecology, mind, and body in an open non-lineary system.

  16. The guinea-pig skin sensitization test revisited: an evaluation formula to predict possible sensitization levels for eight chemicals used in household products.

    PubMed

    Momma, J; Kitajima, S; Inoue, T

    1998-02-20

    In predicting human skin sensitization due to possible risky chemicals, it is not sufficient to evaluate solely the minimum induction dose (MID) or the standard challenge dose (SCD) in the Guinea Pig Maximization Test (GPMT). Nakamura et al. (1994) (Nakamura, A., Momma, J., Sekiguchi, H., Noda, T., Yamano, T., Kaniwa, M., Kojima, S., Tsuda, M., Kurokawa, Y., 1994. A new protocol and criteria for quantitative determination of sensitization potencies of chemicals by guinea pig maximization test. Contact Dermatitis 31, 72-85) previously measured the residual dose of chemicals in the products implicated in human allergic accidents, and stated that '... the level of chemical in the products (direct exposure-dose = DED) was similar to or higher than value of sensitization potency.' However, several of the chemicals listed in their article, show an even lower value of sensitization potency than the DED, although a potential correlation between results of the GPMT and the DED was seemed to be evident; a key question about the essential rule of those parameters therefore remains open. Using the data of Nakamura et al. (1994), we analyzed the functional rules of the three independent parameters, the MID, the SCD, and the DED on which the GPMT is based. Calculations of the degree of allergic reactions elicited in humans provided a range of discrimination constants (D) using the formula; D = DED/(MID*SCD). Possible human allergic accidents may be predicted when the dose of a candidate chemical in a chemical product (equal to DED) exceeds the value; D*(MID*SCD), following the correct evaluation of the MID as well as the SCD.

  17. Multiple spike initiation zones in a neuron implicated in learning in the leech: a computational model.

    PubMed

    Crisp, Kevin M

    2009-03-01

    Sensitization of the defensive shortening reflex in the leech has been linked to a segmentally repeated tri-synaptic positive feedback loop. Serotonin from the R-cell enhances S-cell excitability, S-cell impulses cross an electrical synapse into the C-interneuron, and the C-interneuron excites the R-cell via a glutamatergic synapse. The C-interneuron has two unusual characteristics. First, impulses take longer to propagate from the S soma to the C soma than in the reverse direction. Second, impulses recorded from the electrically unexcitable C soma vary in amplitude when extracellular divalent cation concentrations are elevated, with smaller impulses failing to induce synaptic potentials in the R-cell. A compartmental, computational model was developed to test the sufficiency of multiple, independent spike initiation zones in the C-interneuron to explain these observations. The model displays asymmetric delays in impulse propagation across the S-C electrical synapse and graded impulse amplitudes in the C-interneuron in simulated high divalent cation concentrations.

  18. Different spatial distributions of sodium channels in the slowly and rapidly adapting stretch receptor neuron of the crayfish.

    PubMed

    Lin, J H; Rydqvist, B

    1999-06-05

    Inward Na+ currents were studied, using a two-microelectrode intracellular voltage-clamp technique, in the slowly adapting (SA) and rapidly adapting (RA) stretch receptor neurons of the crayfish after the axons were cut at different distances from the soma. In the SA neuron, inward Na+ currents were recorded in the soma even when the axon was cut as close as 100 microm from the center of the soma, indicating the presence of Na+ channels in these parts. Also, two populations of Na+ channels seem to exist in the SA neuron. In the RA neuron, only minute Na+ currents were observed if the axon was shorter than 250 microm. The results strongly indicate that the voltage-gated Na+ channels in the SA and RA neurons have different distributions and that the difference in the spatial distribution of Na+ channel types may be important for the difference in firing properties in the two types of neurons. Copyright 1999 Elsevier Science B.V.

  19. Axonal autophagosomes recruit dynein for retrograde transport through fusion with late endosomes

    PubMed Central

    Cheng, Xiu-Tang; Zhou, Bing; Lin, Mei-Yao; Cai, Qian

    2015-01-01

    Efficient degradation of autophagic vacuoles (AVs) via lysosomes is an important cellular homeostatic process. This is particularly challenging for neurons because mature acidic lysosomes are relatively enriched in the soma. Although dynein-driven retrograde transport of AVs was suggested, a fundamental question remains how autophagosomes generated at distal axons acquire dynein motors for retrograde transport toward the soma. In this paper, we demonstrate that late endosome (LE)–loaded dynein–snapin complexes drive AV retrograde transport in axons upon fusion of autophagosomes with LEs into amphisomes. Blocking the fusion with syntaxin17 knockdown reduced recruitment of dynein motors to AVs, thus immobilizing them in axons. Deficiency in dynein–snapin coupling impaired AV transport, resulting in AV accumulation in neurites and synaptic terminals. Altogether, our study provides the first evidence that autophagosomes recruit dynein through fusion with LEs and reveals a new motor–adaptor sharing mechanism by which neurons may remove distal AVs engulfing aggregated proteins and dysfunctional organelles for efficient degradation in the soma. PMID:25940348

  20. Alternate Splicing of CD44 Messenger RNA in Prostate Cancer Growth

    DTIC Science & Technology

    2009-04-01

    Higashi M, Kishi H, Hiwasa T, Koda K, Nakajima N, Harigaya K. CD44 signaling through focal adhesion kinase and its anti-apoptotic effect. FEBS Lett...Nakamura, S., Azuma, K., Ishii, G., Higashi, M., Kishi, H., Hiwasa, T., Koda , K., Nakajima, N. and Harigaya, K.: CD44 signaling through focal adhesion

  1. Three descending interneurons reporting deviation from course in the locust. I. Anatomy.

    PubMed

    Griss, C; Rowell, C H

    1986-06-01

    Three descending brain interneurons (DNI, DNM, DNC) are described from Locusta migratoria. All are paired, dorsally situated neurons, with soma in the protocerebrum, input dendrites in the proto- and deuterocerebrum, and a single axon running to the metathoracic ganglion and sometimes further. In DNI the soma and all cerebral arborizations lie ipsilateral to the axon. Discrete regions of arborization lie in the ipsilateral and medial ocellar tracts, the midprotocerebrum and the deuterocerebrum. In the other ganglia the axon branches only ipsilaterally, principally laterally in the flight motor neuropil but also towards the midline. DNC is similarly organized to DNI, but the cell crosses the midline in the brain. Soma, the single projection into a lateral ocellar tract, and the midprotocerebral arborization all lie contralateral to the axon. The deuterocerebral arborization is, however, ipsilateral to the axon. The pattern of projections in the remaining ganglia resembles that of DNI. The soma and all cerebral arborizations of DNM lie ipsilateral to the axon. The arborization is only weakly subdivided into protocerebral, deuterocerebral and medial ocellar tract regions. In the remaining ganglia the arborization extends bilaterally to similar areas of both left and right flight motor neuropil. A table of synonymy is given, equating the various names used for these neurons by previous authors. The morphology correlates well with the known input and output connections. They respond physiologically to deviations from the normal flight posture mediated by ocelli, eyes and wind hairs and connect to the thoracic flight apparatus.

  2. Spinal cord neuron classes in embryos of the smooth newt Triturus vulgaris: a horseradish peroxidase and immunocytochemical study.

    PubMed

    Harper, C E; Roberts, A

    1993-04-29

    Spinal cord neurons were investigated in embryos of Triturus vulgaris, the smooth newt, just prior to hatching. These embryos can swim if freed from their egg membranes. Horseradish peroxidase (HRP) labelling, together with GABA and glycine immunocytochemistry (ICC), revealed nine distinct anatomical classes of neuron. 1. Ventrolateral motoneurons with mainly dorsal dendrites, sometimes a descending central axon and peripheral axon innervating the trunk muscles. 2. Dorsal primary sensory Rohon-Beard neurons innervating skin and with dorsal ascending and descending axons in spinal cord. 3. Commissural interneurons with mid-cord unipolar soma, glycine-like immunoreactivity, dendrites on initial segment of ventral axon which crosses cord to ascend or branch. 4. Dorsolateral commissural interneurons with multipolar soma in dorsolateral position with dorsal dendrites and ventral axon which crosses and ascends or branches. 5. Giant dorsolateral commissural interneurons with large dorsolateral somata widely spaced (130-250 microns spacing) with process projecting dorsally to other side, dorsolateral dendrites and ventral axon which crosses to ascend and branch. 6. Dorsolateral ascending interneurons in dorsolateral position with multipolar soma and ascending axon on same side. 7. Ascending interneurons with unipolar soma, GABA-like immunoreactivity and ascending axon on same side. 8. Descending interneurons with bi- or multi-polar soma, extensive dorsal and ventral dendrites, and descending axon on same side. They may also have ascending axons. 9. Kolmer-Agduhr cerebrospinal fluid contacting neurons with cilia and microvilli in lateral corners of neural canal. GABA-like immunoreactivity, no dendrites and ascending axon. Eight of the nine cells classes were found to bear a marked resemblance to neurons previously described in zebrafish and Xenopus embryos in terms of their anatomy, distribution and immunoreactivity to GABA and glycine. Homologies and possible functions are

  3. Synaptic Democracy and Vesicular Transport in Axons

    NASA Astrophysics Data System (ADS)

    Bressloff, Paul C.; Levien, Ethan

    2015-04-01

    Synaptic democracy concerns the general problem of how regions of an axon or dendrite far from the cell body (soma) of a neuron can play an effective role in neuronal function. For example, stimulated synapses far from the soma are unlikely to influence the firing of a neuron unless some sort of active dendritic processing occurs. Analogously, the motor-driven transport of newly synthesized proteins from the soma to presynaptic targets along the axon tends to favor the delivery of resources to proximal synapses. Both of these phenomena reflect fundamental limitations of transport processes based on a localized source. In this Letter, we show that a more democratic distribution of proteins along an axon can be achieved by making the transport process less efficient. This involves two components: bidirectional or "stop-and-go" motor transport (which can be modeled in terms of advection-diffusion), and reversible interactions between motor-cargo complexes and synaptic targets. Both of these features have recently been observed experimentally. Our model suggests that, just as in human societies, there needs to be a balance between "efficiency" and "equality".

  4. Aβ1-42 triggers the generation of a retrograde signaling complex from sentinel mRNAs in axons.

    PubMed

    Walker, Chandler A; Randolph, Lisa K; Matute, Carlos; Alberdi, Elena; Baleriola, Jimena; Hengst, Ulrich

    2018-05-14

    Neurons frequently encounter neurodegenerative signals first in their periphery. For example, exposure of axons to oligomeric Aβ 1-42 is sufficient to induce changes in the neuronal cell body that ultimately lead to degeneration. Currently, it is unclear how the information about the neurodegenerative insult is transmitted to the soma. Here, we find that the translation of pre-localized but normally silenced sentinel mRNAs in axons is induced within minutes of Aβ 1-42 addition in a Ca 2+ -dependent manner. This immediate protein synthesis following Aβ 1-42 exposure generates a retrograde signaling complex including vimentin. Inhibition of the immediate protein synthesis, knock-down of axonal vimentin synthesis, or inhibition of dynein-dependent transport to the soma prevented the normal cell body response to Aβ 1-42 These results establish that CNS axons react to neurodegenerative insults via the local translation of sentinel mRNAs encoding components of a retrograde signaling complex that transmit the information about the event to the neuronal soma. © 2018 The Authors.

  5. CRS Issue Statement on State and Foreign Operations Appropriations

    DTIC Science & Technology

    2010-01-12

    Moss Analyst in Global Health kmoss@crs.loc.gov, 7-7314 Melissa D. Ho Analyst in Agricultural Policy mho@crs.loc.gov, 7-5342 Kennon H. Nakamura...9525 Jim Nichol Specialist in Russian and Eurasian Affairs jnichol@crs.loc.gov, 7-2289 Charles E. Hanrahan Senior Specialist in Agricultural Policy chanrahan@crs.loc.gov, 7-7235 .

  6. Evolution: the dialogue between life and death

    NASA Astrophysics Data System (ADS)

    Holliday, robin

    1997-12-01

    Organisms have the ability to harness energy from the environment to create order and to reproduce. From early error-prone systems natural selection acted to produce present day organisms with high accuracy in the synthesis of macromolecules. The environment imposes strict limits on reproduction, so evolution is always accompanied by the discarding of a large proportion of the less fit cells, or organisms. Sexual reproduction depends on an immortal germline and a soma which may be immortal or mortal. Higher animals living in hazardous environments have evolved aging and death of the soma for the benefit of the ongoing germline.

  7. Commentary on "Trauma to the Psyche and Soma"

    ERIC Educational Resources Information Center

    Bryant, Richard A.; Hopwood, Sally

    2006-01-01

    This case report addresses assessment and treatment considerations for a patient suffering from posttraumatic stress disorder (PTSD) in the context of mild traumatic brain injury and ongoing pain. Management of this case is based on the application of evidence-based therapy, and of cognitive behaviour therapy, for PTSD reduction. Assessment and…

  8. Clinical Investigation Program. Annual Progress Report

    DTIC Science & Technology

    1990-10-01

    1990 (C) Stevens EL, Venkataraman BW, Southgate M, Nakamura KT: Ontogeny of Sodium Nitroprusside and Atriopeptin III Relaxation in Guinea Pig Airway...of Nephrology Conference, Dec 89 Malinowski TR: Rhabdomyolysis Following Vaccination for Influenza. Hawaii Chapter Scientific Meeting, American College...Muscle Response to Acetylcholine and Histamine. Society for Pediatric Research Meeting, Anaheim, CA, May 90 (C) Stevens EL, Venkataraman BW, Southgate M

  9. Clinical Investigation Program, Reports Control Symbol MED-300(R1), Fiscal Year 1988

    DTIC Science & Technology

    1988-10-01

    Dr. Venkataraman Balaraman, M.D. Department/Section: Clinical Investigation Key Words: arginine vasopressin (AVP); vascular smooth muscle responses...Kullama, Ph.D. Associate Investigators: Dr. Venkataraman Balaraman, M.D.; Dr. Kenneth T. Nakamura, M.D.; John R. Claybaugh, Ph.D. Department/Section...Harrison Hassell, MC Associate Investigators: John R. Claybaugh, Ph.D.; Arnold Siemsen, MD; Jon Streltzer, MD Department/Section: Medicine/ Nephrology

  10. The topography of primate retina: a study of the human, bushbaby, and new- and old-world monkeys.

    PubMed

    Stone, J; Johnston, E

    1981-02-20

    The distribution of ganglion cells has been studied in the retinas of four primates: the prosimian bushbaby, the New-World squirrel monkey, the Old-World crab-eating cynamolgous monkey, and the human. The sizes of ganglion cell somas were also measured at a number of retinal locations and compared with similar measurements in the cat retina to test for the presence in primates of retinal specializations such as the visual streak, and for gradients in retinal structure, such as that between temporal and nasal retina. In all four primates, ganglion cell somas in peripheral retina ranged considerably in diameter (6-16 micrometer in the bushbaby, 8-22 micrometer in the squirrel monkey, 8-23 micrometer in the cynamolgous monkey, 8-26 micrometer in the human). It seems likely that the strong physiological correlates of soma size which have been described among cat retinal ganglion cells and among the relay cells of the macaque lateral geniculate nucleus are generally present in primates. In all four primates, evidence was also obtained of a visual streak specialization; the isodensity lines in ganglion cell density maps were horizontally elongated, and small-bodied ganglion cells were relatively more common in the region of the proposed streak than in other areas of peripheral retina. However, the visual streak seems less well developed than in the cat; among the four primate species examined it was best developed in the bushbaby, at least as assessed by the shape of the isodensity lines. All four primates showed a clear foveal specialization, but this feature seemed least developed in the bushbaby. At the fovea, ganglion cells are smaller in soma size than in peripheral retina; they also seemed more uniform in size, although some distinctly larger cells persist in the human and bushbaby. Soma size measurements also provided evidence of a difference between nasal and temporal areas of peripheral retina comparable to that reported for the cat and other species. Thus the

  11. Spine Calcium Transients Induced by Synaptically-Evoked Action Potentials Can Predict Synapse Location and Establish Synaptic Democracy

    PubMed Central

    Meredith, Rhiannon M.; van Ooyen, Arjen

    2012-01-01

    CA1 pyramidal neurons receive hundreds of synaptic inputs at different distances from the soma. Distance-dependent synaptic scaling enables distal and proximal synapses to influence the somatic membrane equally, a phenomenon called “synaptic democracy”. How this is established is unclear. The backpropagating action potential (BAP) is hypothesised to provide distance-dependent information to synapses, allowing synaptic strengths to scale accordingly. Experimental measurements show that a BAP evoked by current injection at the soma causes calcium currents in the apical shaft whose amplitudes decay with distance from the soma. However, in vivo action potentials are not induced by somatic current injection but by synaptic inputs along the dendrites, which creates a different excitable state of the dendrites. Due to technical limitations, it is not possible to study experimentally whether distance information can also be provided by synaptically-evoked BAPs. Therefore we adapted a realistic morphological and electrophysiological model to measure BAP-induced voltage and calcium signals in spines after Schaffer collateral synapse stimulation. We show that peak calcium concentration is highly correlated with soma-synapse distance under a number of physiologically-realistic suprathreshold stimulation regimes and for a range of dendritic morphologies. Peak calcium levels also predicted the attenuation of the EPSP across the dendritic tree. Furthermore, we show that peak calcium can be used to set up a synaptic democracy in a homeostatic manner, whereby synapses regulate their synaptic strength on the basis of the difference between peak calcium and a uniform target value. We conclude that information derived from synaptically-generated BAPs can indicate synapse location and can subsequently be utilised to implement a synaptic democracy. PMID:22719238

  12. A supercritical density of fast Na+ channels ensures rapid propagation of action potentials in GABAergic interneuron axons

    PubMed Central

    Hu, Hua; Jonas, Peter

    2014-01-01

    Fast-spiking, parvalbumin-expressing GABAergic interneurons/basket cells (BCs) play a key role in feedforward and feedback inhibition, gamma oscillations, and complex information processing. For these functions, fast propagation of action potentials (APs) from the soma to the presynaptic terminals is important. However, the functional properties of interneuron axons remain elusive. Here, we examined interneuron axons by confocally targeted subcellular patch-clamp recording in rat hippocampal slices. APs were initiated in the proximal axon ~20 μm from the soma, and propagated to the distal axon with high reliability and speed. Subcellular mapping revealed a stepwise increase of Na+ conductance density from the soma to the proximal axon, followed by a further gradual increase in the distal axon. Active cable modeling and experiments with partial channel block indicated that low axonal Na+ conductance density was sufficient for reliability, but high Na+ density was necessary for both speed of propagation and fast-spiking AP phenotype. Our results suggest that a supercritical density of Na+ channels compensates for the morphological properties of interneuron axons (small segmental diameter, extensive branching, and high bouton density), ensuring fast AP propagation and high-frequency repetitive firing. PMID:24657965

  13. Contribution of the Axon Initial Segment to Action Potentials Recorded Extracellularly.

    PubMed

    Teleńczuk, Maria; Brette, Romain; Destexhe, Alain; Teleńczuk, Bartosz

    2018-01-01

    Action potentials (APs) are electric phenomena that are recorded both intracellularly and extracellularly. APs are usually initiated in the short segment of the axon called the axon initial segment (AIS). It was recently proposed that at the onset of an AP the soma and the AIS form a dipole. We study the extracellular signature [the extracellular AP (EAP)] generated by such a dipole. First, we demonstrate the formation of the dipole and its extracellular signature in detailed morphological models of a reconstructed pyramidal neuron. Then, we study the EAP waveform and its spatial dependence in models with axonal AP initiation and contrast it with the EAP obtained in models with somatic AP initiation. We show that in the models with axonal AP initiation the dipole forms between somatodendritic compartments and the AIS, and not between soma and dendrites as in the classical models. The soma-dendrites dipole is present only in models with somatic AP initiation. Our study has consequences for interpreting extracellular recordings of single-neuron activity and determining electrophysiological neuron types, but also for better understanding the origins of the high-frequency macroscopic extracellular potentials recorded in the brain.

  14. Time matters for intersex bodies: Between socio-medical time and somatic time.

    PubMed

    Meoded Danon, Limor

    2018-05-08

    This article focuses on the dynamic relationships between time and intersex bodies that exist, on the one hand, in medical policy on intersex bodies and, on the other, in intersex people's subjective experiences. Time, from a sociological perspective, is a biosocial agent that establishes diagnostic practices, regulations, and treatment policy regarding intersex bodies. The systematic construction of timeframes by biomedical professionals aims to rapidly diagnose and treat intersex patients and is deeply rooted in the "dimorphic soma-gender order" (DMSGO), the imagined unified relationship of female bodies to femininity and male bodies to masculinity. From a socio-phenomenological perspective, I describe the concept of somatic time, which involves the relationship between time and the soma, the body's own particular clock and rhythms, according to which it grows, changes, and develops, and the body as a time capsule that stores experiences. I will illustrate the somatic time of intersex people and their subjective embodied experiences of the soma-gender relationship, and explore how their somatic time challenges biomedical timeframes. This qualitative study is based on narrative interviews with biomedical professionals, parents of intersex children, and intersex adults from Israel and Germany. Copyright © 2018 Elsevier Ltd. All rights reserved.

  15. Geometrical Determinants of Neuronal Actin Waves.

    PubMed

    Tomba, Caterina; Braïni, Céline; Bugnicourt, Ghislain; Cohen, Floriane; Friedrich, Benjamin M; Gov, Nir S; Villard, Catherine

    2017-01-01

    Hippocampal neurons produce in their early stages of growth propagative, actin-rich dynamical structures called actin waves. The directional motion of actin waves from the soma to the tip of neuronal extensions has been associated with net forward growth, and ultimately with the specification of neurites into axon and dendrites. Here, geometrical cues are used to control actin wave dynamics by constraining neurons on adhesive stripes of various widths. A key observable, the average time between the production of consecutive actin waves, or mean inter-wave interval (IWI), was identified. It scales with the neurite width, and more precisely with the width of the proximal segment close to the soma. In addition, the IWI is independent of the total number of neurites. These two results suggest a mechanistic model of actin wave production, by which the material conveyed by actin waves is assembled in the soma until it reaches the threshold leading to the initiation and propagation of a new actin wave. Based on these observations, we formulate a predictive theoretical description of actin wave-driven neuronal growth and polarization, which consistently accounts for different sets of experiments.

  16. Geometrical Determinants of Neuronal Actin Waves

    PubMed Central

    Tomba, Caterina; Braïni, Céline; Bugnicourt, Ghislain; Cohen, Floriane; Friedrich, Benjamin M.; Gov, Nir S.; Villard, Catherine

    2017-01-01

    Hippocampal neurons produce in their early stages of growth propagative, actin-rich dynamical structures called actin waves. The directional motion of actin waves from the soma to the tip of neuronal extensions has been associated with net forward growth, and ultimately with the specification of neurites into axon and dendrites. Here, geometrical cues are used to control actin wave dynamics by constraining neurons on adhesive stripes of various widths. A key observable, the average time between the production of consecutive actin waves, or mean inter-wave interval (IWI), was identified. It scales with the neurite width, and more precisely with the width of the proximal segment close to the soma. In addition, the IWI is independent of the total number of neurites. These two results suggest a mechanistic model of actin wave production, by which the material conveyed by actin waves is assembled in the soma until it reaches the threshold leading to the initiation and propagation of a new actin wave. Based on these observations, we formulate a predictive theoretical description of actin wave-driven neuronal growth and polarization, which consistently accounts for different sets of experiments. PMID:28424590

  17. Rab5 and its effector FHF contribute to neuronal polarity through dynein-dependent retrieval of somatodendritic proteins from the axon

    PubMed Central

    Guo, Xiaoli; Farías, Ginny G.; Mattera, Rafael; Bonifacino, Juan S.

    2016-01-01

    An open question in cell biology is how the general intracellular transport machinery is adapted to perform specialized functions in polarized cells such as neurons. Here we illustrate this adaptation by elucidating a role for the ubiquitous small GTPase Ras-related protein in brain 5 (Rab5) in neuronal polarity. We show that inactivation or depletion of Rab5 in rat hippocampal neurons abrogates the somatodendritic polarity of the transferrin receptor and several glutamate receptor types, resulting in their appearance in the axon. This loss of polarity is not caused primarily by increased transport from the soma to the axon but rather by decreased retrieval from the axon to the soma. Retrieval is also dependent on the Rab5 effector Fused Toes (FTS)–Hook–FTS and Hook-interacting protein (FHIP) (FHF) complex, which interacts with the minus-end–directed microtubule motor dynein and its activator dynactin to drive a population of axonal retrograde carriers containing somatodendritic proteins toward the soma. These findings emphasize the importance of both biosynthetic sorting and axonal retrieval for the polarized distribution of somatodendritic receptors at steady state. PMID:27559088

  18. Nova Sco 2011 No. 2 = PNV J16364440-4132340 = PNV J16364300-4132460

    NASA Astrophysics Data System (ADS)

    Waagen, Elizabeth O.

    2011-09-01

    Announcement of discovery of Nova Sco 2011 No. 2 = PNV J16364440-4132340 = PNV J16364300-4132460. Discovered independently by John Seach (Chatsworth Island, NSW, Australia, on 2011 Sep. 06.37 UT at mag=9.8 (DSLR)) and by Yuji Nakamura (Kameyama, Mie, Japan, on 2011 Sep. 06.4313 UT at mag=9.7 C (CCD)). Posted on the IAU Central Bureau for Astronomical Telegrams Transient Object Confirmation Page (TOCP) as PNV J16364440-4132340 (Nakamura) and PNV J16364300-4132460 (Seach); identifications consolidated in VSX under PNV J16364440-4132340. Spectra obtained by A. Arai et al. on 2011 Sep. 7.42 UT suggest a highly reddened Fe II-type classical nova. Spectra by F. Walter and J. Seron obtained Sep. 2011 8.091 UT confirm a young galactic nova; they report spectra are reminiscent of an early recurrent nova. Initially announced in AAVSO Special Notice #251 (Matthew Templeton) and IAU Central Bureau Electronic Telegram 2813 (Daniel W. E. Green, ed.). Finder charts with sequence may be created using the AAVSO Variable Star Plotter (http://www.aavso.org/vsp). Observations should be submitted to the AAVSO International Database. See full Alert Notice for more details and observations.

  19. [Alteration of mitochondrial distribution and gene expression of fission 1 protein in cortical neurons of rats with chronic fluorosis].

    PubMed

    Lou, Di-dong; Zhang, Kai-lin; Qin, Shuang-li; Liu, Yan-fei; Yu, Yan-ni; Guan, Zhi-zhong

    2012-04-01

    To investigate the changes of mitochondrial distribution in axon/soma and the expression of mitochondrial fission 1 (Fis1) protein in the cortical neurons of rats with chronic fluorosis. Sixty SD rats were divided into 3 groups (20 each) according to weight hierarchy and fed with different concentrations of fluoride in drinking water (0, 10 and 50 mg/L, respectively) for 6 months. Images of mitochondria and tubulin labeled by immunofluorescence COXIV and tubulin-α were captured with fluorescence microscope. Fis1 protein expression in cortical neurons was analyzed with immunohistochemistry and Western blot. The expression of Fis1 mRNA was detected with real-time PCR. Varying degrees of dental fluorosis and increased fluoride contents in urine were observed in the rats receiving additional fluoride in drinking water. In the cortical neurons of rats fed with 10 mg/L and 50 mg/L fluoride, the numbers of neuronal soma stained with COXIV(34.8 ± 4.7 and 39.3 ± 3.0, respectively), and the expression of Fis1 protein (immunohistochemistry: 54.0 ± 3.6 and 51.3 ± 4.1, respectively; Western blot: 2.9 ± 0.4 and 2.6 ± 0.6, respectively) and mRNA (3773 ± 1292 and 1274 ± 162, respectively) was markedly increased as compared with controls (4.4 ± 2.3, 25.2 ± 2.5, 1.8 ± 0.2 and 277 ± 73) over the experimental period of 6 months. Excessive intake of fluoride results in an altered mitochondrial distribution in axon and soma in cortical neurons (i.e., the increase in soma and the decrease in axon), increased expression of Fis1 gene and enhanced mitochondrial fission. The altered mitochondrial distribution may be related to the high expression level of Fis1 and a functional disorder of mitochondria.

  20. Identification of genes expressed in the hermaphrodite germ line of C. elegans using SAGE

    PubMed Central

    Wang, Xin; Zhao, Yongjun; Wong, Kim; Ehlers, Peter; Kohara, Yuji; Jones, Steven J; Marra, Marco A; Holt, Robert A; Moerman, Donald G; Hansen, Dave

    2009-01-01

    Background Germ cells must progress through elaborate developmental stages from an undifferentiated germ cell to a fully differentiated gamete. Some of these stages include exiting mitosis and entering meiosis, progressing through the various stages of meiotic prophase, adopting either a male (sperm) or female (oocyte) fate, and completing meiosis. Additionally, many of the factors needed to drive embryogenesis are synthesized in the germ line. To increase our understanding of the genes that might be necessary for the formation and function of the germ line, we have constructed a SAGE library from hand dissected C. elegans hermaphrodite gonads. Results We found that 4699 genes, roughly 21% of all known C. elegans genes, are expressed in the adult hermaphrodite germ line. Ribosomal genes are highly expressed in the germ line; roughly four fold above their expression levels in the soma. We further found that 1063 of the germline-expressed genes have enriched expression in the germ line as compared to the soma. A comparison of these 1063 germline-enriched genes with a similar list of genes prepared using microarrays revealed an overlap of 460 genes, mutually reinforcing the two lists. Additionally, we identified 603 germline-enriched genes, supported by in situ expression data, which were not previously identified. We also found >4 fold enrichment for RNA binding proteins in the germ line as compared to the soma. Conclusion Using multiple technological platforms provides a more complete picture of global gene expression patterns. Genes involved in RNA metabolism are expressed at a significantly higher level in the germ line than the soma, suggesting a stronger reliance on RNA metabolism for control of the expression of genes in the germ line. Additionally, the number and expression level of germ line expressed genes on the X chromosome is lower than expected based on a random distribution. PMID:19426519

  1. The electromotor system of the electric catfish (Malapterurus electricus): a fine-structural analysis.

    PubMed

    Janetzko, A; Zimmermann, H; Volknandt, W

    1987-03-01

    The electromotor system of the electric catfish (Malapterurus electricus) consists of two large ganglion cells situated in the spinal cord, two single axons containing electric nerves and two large electric organs with several million electroplaque cells. The small, irregularly stacked electroplaque cells possess at their center a crater-like indentation from which a stalk like protrusion arises. Many synaptic contacts derived from a single axon collateral are carried on lobe-like protrusions at the terminal knob of this stalk. The electric nerve consists of a large myelinated axon (diameter: 25 micron) surrounded by many layers of connective tissue cells. The two ganglion cells (200 micron in diameter) are rich in elements of the rough endoplasmic reticulum, Golgi apparatus and lysosomal structures. The cytoplasm of the soma changes its appearance towards the voluminous axon hillock (50 micron in diameter) which these organelles do not enter. The cell soma is perforated in a tunnel-like manner by blood capillaries, axons and processes of glial cells. The cell soma and dendrites are covered with two types of synapse. One type forms mixed chemical and electrical (gap junctions) contacts with intermediate attachment plaques. The other type is only chemical in nature. This system may be useful in the study of an identified vertebrate giant neuron.

  2. Second International Meeting on the Molecular Biology and Pathogenesis of the Clostridia.

    DTIC Science & Technology

    1998-06-01

    the Products or services of these Hesearch Council .^"^c^’^a^nUi.S’S. ^re1%o^c^^^ the-invesC?igator (I) "dnered "ilizi^ recombinant DNA technology...Nakamura (Kanazawa Univ., Japon and Lanzhou Inst. of Biological Products , China): Isolation and characterisation of neutro-toxigenic Clostridium...Session 7: Regulation of Virulence Chair: Julian Rood 08:30 T. Shimizu (Tsukuba University, Japan) : Regulation of extracellular toxin production

  3. A sequence of cytoskeleton changes related to the formation of neurofibrillary tangles and neuropil threads.

    PubMed

    Braak, E; Braak, H; Mandelkow, E M

    1994-01-01

    Frontal sections of the temporal lobe including the transentorhinal/entorhinal region, amygdala, and/or hippocampus from human adult brains are studied for cytoskeleton changes using immunostaining with the antibodies AT8 and Alz-50 and selective silver impregnation methods for neurofibrillary changes of the Alzheimer type. For the purpose of correlation, the two methods are carried out one after the other on the same section. Layer pre-alpha in the transentorhinal/entorhinal region harbours nerve cells which are among the first nerve cells in the entire brain to show the development of neurofibrillary changes. This presents the opportunity for study of both early events in the destruction of the cytoskeleton in individual neurons, and to relate changes which occur in the neuronal processes in the absence of alterations in their immediate surroundings to those happening in the soma. Immunoreactions with the AT8 antibody in particular reveal a clear sequence of changes in the neuronal cytoskeleton. Group 1 neurons present initial cytoskeleton changes in that the soma, dendrites, and axon are completely marked by granular AT8 immunoreactive material. These neurons appear quite normal and turn out to be devoid of argyrophilic material when observed in silver-stained sections. Group 2 neurons show changes in the cellular processes. The terminal tuft of the apical dendrite is replaced by tortuous varicose fibres and coarse granules. The distal portions of the dendrites are curved and show appendages and thickened portions. Intensely homogeneously immunostained rod-like inclusions are encountered in these thickened portions and in the soma. A number of these rod-like inclusions are visible after silver staining, as well. Group 3 neurons display even more pronounced alterations of their distal--most dendritic portions. The intermediate dendritic parts lose immunoreactivity, but the soma is homogeneously immunostained. Silver staining reveals in most of the distal

  4. Understanding metal homeostasis in primary cultured neurons. Studies using single neuron subcellular and quantitative metallomics.

    PubMed

    Colvin, Robert A; Lai, Barry; Holmes, William R; Lee, Daewoo

    2015-07-01

    The purpose of this study was to demonstrate how single cell quantitative and subcellular metallomics inform us about both the spatial distribution and cellular mechanisms of metal buffering and homeostasis in primary cultured neurons from embryonic rat brain, which are often used as models of human disease involving metal dyshomeostasis. The present studies utilized synchrotron radiation X-ray fluorescence (SRXRF) and focused primarily on zinc and iron, two abundant metals in neurons that have been implicated in the pathogenesis of neurodegenerative diseases such as Alzheimer's disease and Parkinson's disease. Total single cell contents for calcium, iron, zinc, copper, manganese, and nickel were determined. Resting steady state zinc showed a diffuse distribution in both soma and processes, best defined by the mass profile of the neuron with an enrichment in the nucleus compared with the cytoplasm. Zinc buffering and homeostasis was studied using two modes of cellular zinc loading - transporter and ionophore (pyrithione) mediated. Single neuron zinc contents were shown to statistically significantly increase by either loading method - ionophore: 160 million to 7 billion; transporter 160 million to 280 million atoms per neuronal soma. The newly acquired and buffered zinc still showed a diffuse distribution. Soma and processes have about equal abilities to take up zinc via transporter mediated pathways. Copper levels are distributed diffusely as well, but are relatively higher in the processes relative to zinc levels. Prior studies have observed iron puncta in certain cell types, but others have not. In the present study, iron puncta were characterized in several primary neuronal types. The results show that iron puncta could be found in all neuronal types studied and can account for up to 50% of the total steady state content of iron in neuronal soma. Although other metals can be present in iron puncta, they are predominantly iron containing and do not appear to be

  5. International Workshop on Monokines and Other Non-Lymphocytic Cytokines Held in Hilton Head, South Carolina on 6-10 December 1987.

    DTIC Science & Technology

    1987-12-10

    systems (S. Khadim, Univ. Western Ontario; S. Nakamura, Dainippon Pharm. Co.). Yet TNF has been implicated as the mediator of endotoxin -induced...lethality (J.C. Mathison, Scripps Res. Inst.). In contrast IL-1 appears to provide mice with increased resistance to listeria and pseudomonas infections (C...of IL-1 and TNF, an inhibitor of protein kinase C blocks both IL-1 and TNF mRNA expression in endotoxin stimulated murine macrophages, while an

  6. Twenty-Fifth Annual Conference on the Physics and Chemistry of Semiconductor Interfaces. Volume 16, Number 4

    DTIC Science & Technology

    1998-08-01

    Shigefusa Chichibu, Takayuki Sofa, Kazumi Wada, and Shuji Nakamura Dynamics of localized excitons in InGaN/GaN quantum wells ,. 0 _ _ . w 7onn...Electron. Electron Phys. 11, 413 (1959). 2E. G. Bylander, J. Appl. Phys. 49, 1188 (1978). 3M. Hiraki et al., J. Lumin. 12/13, 941 (1976). 4A. O...University of Tokyo, Noda, Chiba 278-8510, Japan Takayuki Sotab) TT . . . Department of Electrical, Electronics, and Computer Engineering, Waseda

  7. Development and Application of the High Bandwidth Powered Resonance Tube

    DTIC Science & Technology

    2005-11-09

    arises in practical situations. In laser cutting, it is a common practice to remove the molten mass of metal with the help of high speed jet of air...cleaner and straighter laser cuts[Masuda and Nakamura, 19921. Thin glass sheets are prone to cracks when tempered by a cold air jet with impingement...Alvi, F. S., Shish, C., Elavarasan, R., Garg, G., and Krothapalli, A., 2003. Control of supersonic impinging jet flows using supersonic microjets

  8. Action potentials in retinal ganglion cells are initiated at the site of maximal curvature of the extracellular potential.

    PubMed

    Eickenscheidt, Max; Zeck, Günther

    2014-06-01

    The initiation of an action potential by extracellular stimulation occurs after local depolarization of the neuronal membrane above threshold. Although the technique shows remarkable clinical success, the site of action and the relevant stimulation parameters are not completely understood. Here we identify the site of action potential initiation in rabbit retinal ganglion cells (RGCs) interfaced to an array of extracellular capacitive stimulation electrodes. We determine which feature of the extracellular potential governs action potential initiation by simultaneous stimulation and recording RGCs interfaced in epiretinal configuration. Stimulation electrodes were combined to areas of different size and were presented at different positions with respect to the RGC. Based on stimulation by electrodes beneath the RGC soma and simultaneous sub-millisecond latency measurement we infer axonal initiation at the site of maximal curvature of the extracellular potential. Stimulation by electrodes at different positions along the axon reveals a nearly constant threshold current density except for a narrow region close to the cell soma. These findings are explained by the concept of the activating function modified to consider a region of lower excitability close to the cell soma. We present a framework how to estimate the site of action potential initiation and the stimulus required to cross threshold in neurons tightly interfaced to capacitive stimulation electrodes. Our results underscore the necessity of rigorous electrical characterization of the stimulation electrodes and of the interfaced neural tissue.

  9. Democratization in a passive dendritic tree: an analytical investigation.

    PubMed

    Timofeeva, Y; Cox, S J; Coombes, S; Josić, K

    2008-10-01

    One way to achieve amplification of distal synaptic inputs on a dendritic tree is to scale the amplitude and/or duration of the synaptic conductance with its distance from the soma. This is an example of what is often referred to as "dendritic democracy". Although well studied experimentally, to date this phenomenon has not been thoroughly explored from a mathematical perspective. In this paper we adopt a passive model of a dendritic tree with distributed excitatory synaptic conductances and analyze a number of key measures of democracy. In particular, via moment methods we derive laws for the transport, from synapse to soma, of strength, characteristic time, and dispersion. These laws lead immediately to synaptic scalings that overcome attenuation with distance. We follow this with a Neumann approximation of Green's representation that readily produces the synaptic scaling that democratizes the peak somatic voltage response. Results are obtained for both idealized geometries and for the more realistic geometry of a rat CA1 pyramidal cell. For each measure of democratization we produce and contrast the synaptic scaling associated with treating the synapse as either a conductance change or a current injection. We find that our respective scalings agree up to a critical distance from the soma and we reveal how this critical distance decreases with decreasing branch radius.

  10. Active signal conduction through the sensory dendrite of a spider mechanoreceptor neuron.

    PubMed

    Gingl, Ewald; French, Andrew S

    2003-07-09

    Rapid responses to sensory stimulation are crucial for survival. This must be especially true for mechanical stimuli containing temporal information, such as vibration. Sensory transduction occurs at the tips of relatively long sensory dendrites in many mechanoreceptors of both vertebrates and invertebrates, but little is known about the electrical properties of these crucial links between transduction and action potential generation. The VS-3 slit-sense organ of the spider Cupiennius salei contains bipolar mechanosensory neurons that allow voltage-clamp recording from the somata, whereas mechanotransduction occurs at the tips of 100- to 200-microm-long sensory dendrites. We studied the properties of VS-3 sensory dendrites using three approaches. Voltage-jump experiments measured the spread of voltage outward from the soma by observing total mechanically transduced charge recovered at the soma as a function of time after a voltage jump. Frequency-response measurements between pseudorandom mechanical stimulation and somatic membrane potential estimated the passive cable properties of the dendrite for voltage spread in the opposite direction. Both of these sets of data indicated that the dendritic cable would significantly attenuate and retard a passively propagated receptor potential. Finally, current-clamp observations of receptor potentials and action potentials indicated that action potentials normally start at the distal dendrites and propagate regeneratively to the soma, reducing the temporal delay of passive conduction.

  11. Longevity and transposon defense, the case of termite reproductives

    PubMed Central

    Elsner, Daniel; Meusemann, Karen; Korb, Judith

    2018-01-01

    Social insects are promising new models in aging research. Within single colonies, longevity differences of several magnitudes exist that can be found elsewhere only between different species. Reproducing queens (and, in termites, also kings) can live for several decades, whereas sterile workers often have a lifespan of a few weeks only. We studied aging in the wild in a highly social insect, the termite Macrotermes bellicosus, which has one of the most pronounced longevity differences between reproductives and workers. We show that gene-expression patterns differed little between young and old reproductives, implying negligible aging. By contrast, old major workers had many genes up-regulated that are related to transposable elements (TEs), which can cause aging. Strikingly, genes from the PIWI-interacting RNA (piRNA) pathway, which are generally known to silence TEs in the germline of multicellular animals, were down-regulated only in old major workers but not in reproductives. Continued up-regulation of the piRNA defense commonly found in the germline of animals can explain the long life of termite reproductives, implying somatic cooption of germline defense during social evolution. This presents a striking germline/soma analogy as envisioned by the superorganism concept: the reproductives and workers of a colony reflect the germline and soma of multicellular animals, respectively. Our results provide support for the disposable soma theory of aging. PMID:29735660

  12. Method to investigate temporal dynamics of ganglion and other retinal cells in the living human eye

    NASA Astrophysics Data System (ADS)

    Kurokawa, Kazuhiro; Liu, Zhuolin; Crowell, James; Zhang, Furu; Miller, Donald T.

    2018-02-01

    The inner retina is critical for visual processing, but much remains unknown about its neural circuitry and vulnerability to disease. A major bottleneck has been our inability to observe the structure and function of the cells composing these retinal layers in the living human eye. Here, we present a noninvasive method to observe both structural and functional information. Adaptive optics optical coherence tomography (AO-OCT) is used to resolve the inner retinal cells in all three dimensions and novel post processing algorithms are applied to extract structure and physiology down to the cellular level. AO-OCT captured the 3D mosaic of individual ganglion cell somas, retinal nerve fiber bundles of micron caliber, and microglial cells, all in exquisite detail. Time correlation analysis of the AO-OCT videos revealed notable temporal differences between the principal layers of the inner retina. The GC layer was more dynamic than the nerve fiber and inner plexiform layers. At the cellular level, we applied a customized correlation method to individual GCL somas, and found a mean time constant of activity of 0.57 s and spread of +/-0.1 s suggesting a range of physiological dynamics even in the same cell type. Extending our method to slower dynamics (from minutes to one year), time-lapse imaging and temporal speckle contrast revealed appendage and soma motion of resting microglial cells at the retinal surface.

  13. Evolution of aging: individual life history trade-offs and population heterogeneity account for mortality patterns across species.

    PubMed

    Le Cunff, Y; Baudisch, A; Pakdaman, K

    2014-08-01

    A broad range of mortality patterns has been documented across species, some even including decreasing mortality over age. Whether there exist a common denominator to explain both similarities and differences in these mortality patterns remains an open question. The disposable soma theory, an evolutionary theory of aging, proposes that universal intracellular trade-offs between maintenance/lifespan and reproduction would drive aging across species. The disposable soma theory has provided numerous insights concerning aging processes in single individuals. Yet, which specific population mortality patterns it can lead to is still largely unexplored. In this article, we propose a model exploring the mortality patterns which emerge from an evolutionary process including only the disposable soma theory core principles. We adapt a well-known model of genomic evolution to show that mortality curves producing a kink or mid-life plateaus derive from a common minimal evolutionary framework. These mortality shapes qualitatively correspond to those of Drosophila melanogaster, Caenorhabditis elegans, medflies, yeasts and humans. Species evolved in silico especially differ in their population diversity of maintenance strategies, which itself emerges as an adaptation to the environment over generations. Based on this integrative framework, we also derive predictions and interpretations concerning the effects of diet changes and heat-shock treatments on mortality patterns. © 2014 The Authors. Journal of Evolutionary Biology © 2014 European Society For Evolutionary Biology.

  14. Modulation of spike coding by subthreshold extracellular electric fields and neuronal morphology

    NASA Astrophysics Data System (ADS)

    Wei, Xile; Li, Bingjie; Lu, Meili; Yi, Guosheng; Wang, Jiang

    2015-07-01

    We use a two-compartment model, which includes soma and dendrite, to explore how extracellular subthreshold sinusoidal electric fields (EFs) influence the spike coding of an active neuron. By changing the intensity and the frequency of subthreshold EFs, we find that subthreshold EFs indeed affect neuronal coding remarkably within several stimulus frequency windows where the field effects on spike timing are stronger than that on spiking rate. The field effects are maximized at several harmonics of the intrinsic spiking frequency of an active neuron. Our findings implicate the potential resonance mechanism underlying subthreshold field effects. We also discuss how neuronal morphologic properties constrain subthreshold EF effects on spike timing. The morphologic properties are represented by two parameters, gc and p, where gc is the internal conductance between soma and dendrite and geometric factor p characterizes the proportion of area occupied by soma. We find that the contribution to field effects from the variation of p is stronger than that from gc, which suggests that neuronal geometric features play a crucial role in subthreshold field effects. Theoretically, these insights into how subthreshold sinusoidal EFs modulate ongoing neuron behaviors could contribute to uncovering the relevant mechanism of subthreshold sinusoidal EFs effects on neuronal coding. Furthermore, they are useful in rationally designing noninvasive brain stimulation strategies and developing electromagnetic stimulus techniques.

  15. The morphology and electrical geometry of rat jaw-elevator motoneurones.

    PubMed Central

    Moore, J A; Appenteng, K

    1991-01-01

    1. The aim of this work was to quantify both the morphology and electrical geometry of the dendritic trees of jaw-elevator motoneurones. To do this we have made intracellular recordings from identified motoneurones in anaesthetized rats, determined their membrane properties and then filled them with horseradish peroxidase by ionophoretic ejection. Four neurones were subsequently fully reconstructed and the lengths and diameters of all the dendritic segments measured. 2. The mean soma diameter was 25 microns and values of mean dendritic length for individual cells ranged from 514 to 773 microns. Dendrites branched on average 9.1 times to produce 10.2 end-terminations. Dendritic segments could be represented as constant diameter cylinders between branch points. Values of dendritic surface area ranged from 1.08 to 2.52 x 10(5) microns 2 and values of dendritic to total surface area from 98 to 99%. 3. At branch points the ratio of the summed diameters of the daughter dendrites to the 3/2 power against the parent dendrite to the 3/2 power was exactly 1.0. Therefore the individual branch points could be collapsed into a single cylinder. Furthermore for an individual dendrite the diameter of this cylinder remained constant with increasing electrical distance from the soma. Thus individual dendrites can be represented electrically as cylinders of constant diameter. 4. However dendrites of a given neurone terminated at different electrical distances from the soma. The equivalent-cylinder diameter of the combined dendritic tree remained constant over the proximal half and then showed a pronounced reduction over the distal half. The reduction in equivalent diameter could be ascribed to the termination of dendrites at differing electrical distances from the soma. Therefore the complete dendritic tree of these motoneurones is best represented as a cylinder over the proximal half of their electrical length but as a cone over the distal half. PMID:1804966

  16. Sexual Fate Reprogramming in the Steroid-Induced Bi-Directional Sex Change in the Protogynous Orange-Spotted Grouper, Epinephelus coioides.

    PubMed

    Wu, Guan-Chung; Tey, Wei-Guan; Li, Hau-Wen; Chang, Ching-Fong

    2015-01-01

    Androgen administration has been widely used for masculinization in fish. The mechanism of the sex change in sexual fate regulation is not clear. Oral administration or pellet implantation was applied. We orally applied an aromatase inhibitor (AI, to decrease estrogen levels) and 17α-methyltestosterone (MT, to increase androgen levels) to induce masculinization to clarify the mechanism of the sex change in the protogynous orange-spotted grouper. After 3 mo of AI/MT administration, male characteristics were observed in the female-to-male sex change fish. These male characteristics included increased plasma 11-ketotestosterone (11-KT), decreased estradiol (E2) levels, increased male-related gene (dmrt1, sox9, and cyp11b2) expression, and decreased female-related gene (figla, foxl2, and cyp19a1a) expression. However, the reduced male characteristics and male-to-female sex change occurred after AI/MT-termination in the AI- and MT-induced maleness. Furthermore, the MT-induced oocyte-depleted follicle cells (from MT-implantation) had increased proliferating activity, and the sexual fate in a portion of female gonadal soma cells was altered to male function during the female-to-male sex change. In contrast, the gonadal soma cells were not proliferative during the early process of the male-to-female sex change. Additionally, the male gonadal soma cells did not alter to female function during the male-to-female sex change in the AI/MT-terminated fish. After MT termination in the male-to-female sex-changed fish, the differentiated male germ cells showed increased proliferating activities together with dormancy and did not show characteristics of both sexes in the early germ cells. In conclusion, these findings indicate for the first time in a single species that the mechanism involved in the replacement of soma cells is different between the female-to-male and male-to-female sex change processes in grouper. These results also demonstrate that sexual fate determination

  17. Sexual Fate Reprogramming in the Steroid-Induced Bi-Directional Sex Change in the Protogynous Orange-Spotted Grouper, Epinephelus coioides

    PubMed Central

    Wu, Guan-Chung; Tey, Wei-Guan; Li, Hau-Wen; Chang, Ching-Fong

    2015-01-01

    Androgen administration has been widely used for masculinization in fish. The mechanism of the sex change in sexual fate regulation is not clear. Oral administration or pellet implantation was applied. We orally applied an aromatase inhibitor (AI, to decrease estrogen levels) and 17α-methyltestosterone (MT, to increase androgen levels) to induce masculinization to clarify the mechanism of the sex change in the protogynous orange-spotted grouper. After 3 mo of AI/MT administration, male characteristics were observed in the female-to-male sex change fish. These male characteristics included increased plasma 11-ketotestosterone (11-KT), decreased estradiol (E2) levels, increased male-related gene (dmrt1, sox9, and cyp11b2) expression, and decreased female-related gene (figla, foxl2, and cyp19a1a) expression. However, the reduced male characteristics and male-to-female sex change occurred after AI/MT-termination in the AI- and MT-induced maleness. Furthermore, the MT-induced oocyte-depleted follicle cells (from MT-implantation) had increased proliferating activity, and the sexual fate in a portion of female gonadal soma cells was altered to male function during the female-to-male sex change. In contrast, the gonadal soma cells were not proliferative during the early process of the male-to-female sex change. Additionally, the male gonadal soma cells did not alter to female function during the male-to-female sex change in the AI/MT-terminated fish. After MT termination in the male-to-female sex-changed fish, the differentiated male germ cells showed increased proliferating activities together with dormancy and did not show characteristics of both sexes in the early germ cells. In conclusion, these findings indicate for the first time in a single species that the mechanism involved in the replacement of soma cells is different between the female-to-male and male-to-female sex change processes in grouper. These results also demonstrate that sexual fate determination

  18. Characterization of Polar, Semi-Polar, and Non-Polar p-n Homo and Hetero-junctions grown by Ammonia Molecular Beam Epitaxy

    NASA Astrophysics Data System (ADS)

    Hurni, Christophe Antoine

    Widespread interest in the group III-Nitrides began with the achievement of p-type conductivity in the early 1990s in Mg-doped GaN films grown by metal organic chemical vapor deposition (MOCVD) by Nakamura et al. Indeed, MOCVD-grown Mg-doped GaN is insulating as-grown, because of the formation of neutral Mg-H complexes. Nakamura et al. showed that a rapid thermal anneal removes the hydrogen and enables p-conductivity. Shortly after this discovery, the first LEDs and lasers were demonstrated by Nakamura et al. The necessary annealing step is problematic for devices which need a buried p-layer, such as hetero-junction bipolar transistors. Ammonia molecular beam epitaxy (NH3-MBE) has a great potential for growing vertical III-Nitrides-based devices, thank to its N-rich growth conditions and all the usual advantages of MBE, which include a low-impurity growth environment, in situ monitoring techniques as well as the ability to grow sharp interfaces. We first investigated the growth of p-GaN by NH3-MBE. We found that the hole concentration strongly depends on the growth temperature. Thanks to comprehensive Hall and transfer length measurements, we found evidences for a compensating donor defects in NH3-MBE-grown Mg-doped GaN films. High-quality p-n junctions with very low reverse current and close to unity ideality factor were also grown and investigated. For the design of heterojunction devices such as laser diodes, light emitting diodes or heterojunction bipolar transistors, hetero-interface's characteristics such as the band offset or interface charges are fundamental. A technique developed by Kroemer et al. uses capacitance-voltage (C-V) profiling to extract band-offsets and charges at a hetero-interface. We applied this technique to the III-Nitrides. We discovered that for the polar III-Nitrides, the technique is not applicable because of the very large polarization charge. We nevertheless successfully measured the polarization charge at the AlGaN/GaN hetero

  19. A numerical study of the 3-periodic wave solutions to KdV-type equations

    NASA Astrophysics Data System (ADS)

    Zhang, Yingnan; Hu, Xingbiao; Sun, Jianqing

    2018-02-01

    In this paper, by using the direct method of calculating periodic wave solutions proposed by Akira Nakamura, we present a numerical process to calculate the 3-periodic wave solutions to several KdV-type equations: the Korteweg-de Vries equation, the Sawada-Koterra equation, the Boussinesq equation, the Ito equation, the Hietarinta equation and the (2 + 1)-dimensional Kadomtsev-Petviashvili equation. Some detailed numerical examples are given to show the existence of the three-periodic wave solutions numerically.

  20. Single Microwave-Photon Detector using an Artificial Lambda-type Three-Level System

    DTIC Science & Technology

    2016-01-11

    Single microwave-photon detector using an artificial Λ-type three- level system Kunihiro Inomata,1∗†, Zhirong Lin,1†, Kazuki Koshino,2, William D...three- level system Kunihiro Inomata,1∗† Zhirong Lin,1† Kazuki Koshino,2 William D. Oliver,3,4 Jaw-Shen Tsai,1 Tsuyoshi Yamamoto,5 Yasunobu Nakamura...single-microwave-photon detector based on the deterministic switching in an artificial Λ-type three- level system implemented using the dressed states of a

  1. A Guide to Electrical Insulation Design in Aerospace Vehicles for a Broad Range of Environmental Parameter Space

    DTIC Science & Technology

    2010-03-01

    as an example with information from Llewellyn Jones (1939) [30] and from Meek (1978), pg. 233 [7]. Morokuma (1969) [31] varied the surface potential...breakdown in high pressure gases,” Phys. Rev. A, 21, 2069. 13. Dutton, J., Llewellyn Jones , F., and Palmer, R.W., (1961), Proc. Phys. Soc. 78, 569...breakdown and insulators in compressed gas,” IEE Proc. 128, 303. 30. Llewellyn Jones , F. (1939), Phil. Mag. 28, 192. 31. Morokuma, Y., Nakamura, Y., and

  2. Epitaxial Growths of m-Plane AlGaN/GaN and AlInN/GaN Heterostructures Applicable for Normally-Off Mode High Power Field Effect Transistors on Freestanding GaN Substrates

    DTIC Science & Technology

    2011-08-17

    cathodoluminescence (CL), and Hall effect measurement. We will disclose how structural and point defects affect the internal quantum efficiency. We have a complete...18. S. F. Chichibu, A. Uedono, T. Onuma, S. P. DenBaars, U. K. Mishra, J. S. Speck, and S. Nakamura, “Impact of Point Defects on the Luminescence...A. Uedono, “Major impacts of point defects and impurities on the carrier recombination dynamics in AlN,” Appl. Phys. Lett. 97(20), 201904 (2010

  3. Scanning Tunneling Microscopy, Atomic Force Microscopy, and Related Techniques

    DTIC Science & Technology

    1992-02-26

    92. (B47) Fujui, T.; Suzuki, MA.; Miyashita, MA.; Yamaguchi, M.; Onuki , T.; Nakamura, H .; Matsubara, T.; Yamada, H .; Nakayamia, K. J. Vac. Sd...and seven deflection detection systems (A 15). (Al) Binnig, G.; Rohrer, H .; Gerber, Ch.; Weibel, E. Phys. Rev. Lett. 1982, 49, 57. (A2) Ray, M.A...J. J. Vac Sci. Technol. A 1ඣ, 9, 44-50. (AS) Scanning Tunneling Microscopy and Related Methods; Behm, RJ., Garcia, N., Rohrer, H ., Eds.; NATO ASI

  4. Determination of NEHRP Site Class of Seismic Recording Stations in the Northwest Himalayas and Its Adjoining Area Using HVSR Method

    NASA Astrophysics Data System (ADS)

    Harinarayan, N. H.; Kumar, Abhishek

    2018-01-01

    Local site characteristics play an important role in controlling the damage pattern during earthquakes (EQs). These site characteristics may vary from simple to complex and can be estimated by various field tests. In addition, extended Nakamura's method, which uses horizontal to vertical spectral ratio (HVSR) based on available EQ records also available for site class (SC) determination. In this study, SCs for 90 recording stations which are maintained by Program for Excellence in Strong Motion Studies (PESMOS), located in the northwestern Himalayas and the adjoining areas are determined using extended Nakamura's technique. Average HVSR curves obtained at majority of the recording stations are found matching with the existing literature. Predominant frequency ( f peak) from average HVSR curve at each recording station is then used for the determination of SC. Original SC given by PESMOS is purely based on geology and not based on comprehensive soil investigation exercise. In this study, the SC, which is based on the average HVSR curves is found matching with SC given by PESMOS for a majority of recording stations. However, for considerable number of recording stations, a mismatch is also found which is consistent with the existing literature. In addition, SC based on National Earthquake Hazard Reduction Program (NEHRP) scheme is proposed based on f peak for all the 90 recording stations.

  5. Epigenetic Programming of Breast Cancer and Nutrition Prevention

    DTIC Science & Technology

    2012-05-01

    to control (Figure 2). Maternal dietary supplementation with Res reduced by ~60% DNMT1 occupancy on the BRCA-1 promoter, compared with TCDD exposed...2009;75:1227–30. [57] Jeuken A, Keser BJ, Khan E, Brouwer A, Koeman J, DenisonMS. Activation of the Ah receptor by extracts of dietary herbal ... supplements , vegetables, and fruits. J Agric Food Chem 2003;51:5478–87. [58] Amakura Y, Tsutsumi T, Sasaki K, Nakamura M, Yoshida T, Maitani T. Influence of

  6. Role of microRNA in Aggressive Prostate Cancer

    DTIC Science & Technology

    2015-09-01

    j.issn.2223-4683.2013.08.01 Scan to your mobile device or view this article at: http://www.amepc.org/tau/article/view/2550/3635 229Translational Andrology...of Ezh2, accompanied with diminished clonogenic ability and sphere formation in PCa cells (45). Another let-7 target gene is High- mobility group AT...2013;32:4139-47. 89. Motoyama K, Inoue H, Nakamura Y, et al. Clinical significance of high mobility group A2 in human gastric cancer and its

  7. Generating synchrony from the asynchronous: compensation for cochlear traveling wave delays by the dendrites of individual brainstem neurons

    PubMed Central

    McGinley, Matthew J.; Liberman, M. Charles; Bal, Ramazan; Oertel, Donata

    2012-01-01

    Broadband transient sounds, such as clicks and consonants, activate a traveling wave in the cochlea. This wave evokes firing in auditory nerve fibers that are tuned to high frequencies several milliseconds earlier than in fibers tuned to low frequencies. Despite this substantial traveling wave delay, octopus cells in the brainstem receive broadband input and respond to clicks with submillisecond temporal precision. The dendrites of octopus cells lie perpendicular to the tonotopically organized array of auditory nerve fibers, placing the earliest arriving inputs most distally and the latest arriving closest to the soma. Here, we test the hypothesis that the topographic arrangement of synaptic inputs on dendrites of octopus cells allows octopus cells to compensate the traveling wave delay. We show that in mice the full cochlear traveling wave delay is 1.6 ms. Because the dendrites of each octopus cell spread across about one third of the tonotopic axis, a click evokes a soma directed sweep of synaptic input lasting 0.5 ms in individual octopus cells. Morphologically and biophysically realistic, computational models of octopus cells show that soma-directed sweeps with durations matching in vivo measurements result in the largest and sharpest somatic excitatory postsynaptic potentials (EPSPs). A low input resistance and activation of a low-voltage-activated potassium conductance that are characteristic of octopus cells are important determinants of sweep sensitivity. We conclude that octopus cells have dendritic morphologies and biophysics tailored to accomplish the precise encoding of broadband transient sounds. PMID:22764237

  8. Postsynaptic degeneration as revealed by PSD-95 reduction occurs after advanced Aβ and tau pathology in transgenic mouse models of Alzheimer's disease.

    PubMed

    Shao, Charles Y; Mirra, Suzanne S; Sait, Hameetha B R; Sacktor, Todd C; Sigurdsson, Einar M

    2011-09-01

    Impairment of synaptic plasticity underlies memory dysfunction in Alzheimer's disease (AD). Molecules involved in this plasticity such as PSD-95, a major postsynaptic scaffold protein at excitatory synapses, may play an important role in AD pathogenesis. We examined the distribution of PSD-95 in transgenic mice of amyloidopathy (5XFAD) and tauopathy (JNPL3) as well as in AD brains using double-labeling immunofluorescence and confocal microscopy. In wild type control mice, PSD-95 primarily labeled neuropil with distinct distribution in hippocampal apical dendrites. In 3-month-old 5XFAD mice, PSD-95 distribution was similar to that of wild type mice despite significant Aβ deposition. However, in 6-month-old 5XFAD mice, PSD-95 immunoreactivity in apical dendrites markedly decreased and prominent immunoreactivity was noted in neuronal soma in CA1 neurons. Similarly, PSD-95 immunoreactivity disappeared from apical dendrites and accumulated in neuronal soma in 14-month-old, but not in 3-month-old, JNPL3 mice. In AD brains, PSD-95 accumulated in Hirano bodies in hippocampal neurons. Our findings support the notion that either Aβ or tau can induce reduction of PSD-95 in excitatory synapses in hippocampus. Furthermore, this PSD-95 reduction is not an early event but occurs as the pathologies advance. Thus, the time-dependent PSD-95 reduction from synapses and accumulation in neuronal soma in transgenic mice and Hirano bodies in AD may mark postsynaptic degeneration that underlies long-term functional deficits.

  9. The expression of hyperpolarization-activated cyclic nucleotide-gated channel 1 (HCN1) and HCN2 in the rat trigeminal ganglion, sensory root, and dental pulp.

    PubMed

    Cho, Y S; Kim, Y S; Moozhayil, S J; Yang, E S; Bae, Y C

    2015-04-16

    Hyperpolarization-activated cyclic nucleotide-gated channel 1 (HCN1) and 2 (HCN2) are abundantly expressed in primary sensory neurons and contribute to neuronal excitability and pathological pain. We studied the expression of HCN1 and HCN2 in the rat trigeminal ganglion (TG) neurons and axons in the dental pulp, and the changes in their expression following inflammation, using light- and electron-microscopic immunocytochemistry and quantitative analysis. HCN1 and HCN2 were expressed predominantly in large-sized, neurofilament 200-immunopositive (+) or parvalbumin+ soma in the TG whereas they were expressed mostly in unmyelinated and small myelinated axons in the sensory root. The expression was particularly strong along the plasma membrane in the soma. In the dental pulp, majority of HCN1+ and HCN2+ axons coexpressed calcitonin gene-related peptide. They were expressed mainly in the peripheral pulp and pulp horn where the axons branch extensively in the dental pulp. The expression of HCN1 and HCN2 in TG neurons increased significantly in rats with experimentally induced inflammation of the dental pulp. Our findings support the notion that HCN1 and HCN2 are expressed mainly by both the soma of mechanosensitive neurons in the TG and peripheral axons of nociceptive neurons in the sensory root, and may play a role in the mechanisms of inflammatory pain from the dental pulp. Copyright © 2015 IBRO. Published by Elsevier Ltd. All rights reserved.

  10. Hierarchical control of motor units in voluntary contractions.

    PubMed

    De Luca, Carlo J; Contessa, Paola

    2012-01-01

    For the past five decades there has been wide acceptance of a relationship between the firing rate of motor units and the afterhyperpolarization of motoneurons. It has been promulgated that the higher-threshold, larger-soma, motoneurons fire faster than the lower-threshold, smaller-soma, motor units. This relationship was based on studies on anesthetized cats with electrically stimulated motoneurons. We questioned its applicability to motor unit control during voluntary contractions in humans. We found that during linearly force-increasing contractions, firing rates increased as exponential functions. At any time and force level, including at recruitment, the firing rate values were inversely related to the recruitment threshold of the motor unit. The time constants of the exponential functions were directly related to the recruitment threshold. From the Henneman size principle it follows that the characteristics of the firing rates are also related to the size of the soma. The "firing rate spectrum" presents a beautifully simple control scheme in which, at any given time or force, the firing rate value of earlier-recruited motor units is greater than that of later-recruited motor units. This hierarchical control scheme describes a mechanism that provides an effective economy of force generation for the earlier-recruited lower force-twitch motor units, and reduces the fatigue of later-recruited higher force-twitch motor units-both characteristics being well suited for generating and sustaining force during the fight-or-flight response.

  11. Hierarchical control of motor units in voluntary contractions

    PubMed Central

    Contessa, Paola

    2012-01-01

    For the past five decades there has been wide acceptance of a relationship between the firing rate of motor units and the afterhyperpolarization of motoneurons. It has been promulgated that the higher-threshold, larger-soma, motoneurons fire faster than the lower-threshold, smaller-soma, motor units. This relationship was based on studies on anesthetized cats with electrically stimulated motoneurons. We questioned its applicability to motor unit control during voluntary contractions in humans. We found that during linearly force-increasing contractions, firing rates increased as exponential functions. At any time and force level, including at recruitment, the firing rate values were inversely related to the recruitment threshold of the motor unit. The time constants of the exponential functions were directly related to the recruitment threshold. From the Henneman size principle it follows that the characteristics of the firing rates are also related to the size of the soma. The “firing rate spectrum” presents a beautifully simple control scheme in which, at any given time or force, the firing rate value of earlier-recruited motor units is greater than that of later-recruited motor units. This hierarchical control scheme describes a mechanism that provides an effective economy of force generation for the earlier-recruited lower force-twitch motor units, and reduces the fatigue of later-recruited higher force-twitch motor units—both characteristics being well suited for generating and sustaining force during the fight-or-flight response. PMID:21975447

  12. Directional ratio based on parabolic molecules and its application to the analysis of tubular structures

    NASA Astrophysics Data System (ADS)

    Labate, Demetrio; Negi, Pooran; Ozcan, Burcin; Papadakis, Manos

    2015-09-01

    As advances in imaging technologies make more and more data available for biomedical applications, there is an increasing need to develop efficient quantitative algorithms for the analysis and processing of imaging data. In this paper, we introduce an innovative multiscale approach called Directional Ratio which is especially effective to distingush isotropic from anisotropic structures. This task is especially useful in the analysis of images of neurons, the main units of the nervous systems which consist of a main cell body called the soma and many elongated processes called neurites. We analyze the theoretical properties of our method on idealized models of neurons and develop a numerical implementation of this approach for analysis of fluorescent images of cultured neurons. We show that this algorithm is very effective for the detection of somas and the extraction of neurites in images of small circuits of neurons.

  13. A conversation across generations: soma-germ cell crosstalk in plants.

    PubMed

    Feng, Xiaoqi; Zilberman, Daniel; Dickinson, Hugh

    2013-02-11

    Plants undergo alternation of generation in which reproductive cells develop in the plant body ("sporophytic generation") and then differentiate into a multicellular gamete-forming "gametophytic generation." Different populations of helper cells assist in this transgenerational journey, with somatic tissues supporting early development and single nurse cells supporting gametogenesis. New data reveal a two-way relationship between early reproductive cells and their helpers involving complex epigenetic and signaling networks determining cell number and fate. Later, the egg cell plays a central role in specifying accessory cells, whereas in both gametophytes, companion cells contribute non-cell-autonomously to the epigenetic landscape of the gamete genomes. Copyright © 2013 Elsevier Inc. All rights reserved.

  14. The History of Mind (Psyche)-Body (Soma) Medicine: Practical Examples.

    PubMed

    Martins, Paulo Nuno

    2018-01-01

    This article discusses the relationship between health and disease, considering the mind/body dichotomy that has occurred in the history of medicine, both in Western and Eastern cultures. The author begins by referring to the magical concept of disease, passing through the classical Greek period, and the medieval and Renaissance vision, to the evolution of modern concepts proposed by psychoanalysis. The author references some practical examples about the importance of the mind-body relationship, such as the psychological steps experienced by the oncological patient, as well as the psychiatric disorder.

  15. [Psyche and soma: what can the consultation-liaison psychiatrist contribute?].

    PubMed

    Diefenbacher, Albert

    2015-01-01

    In German speaking countries, during the last decades, we can see a growing, though albeit small, integration of psychiatry and psychosomatics into (somatic) medicine. This article outlines the importance of the growing number of elderly patients in medical care as a vantage point for c-l-psychiatrists to play a pro-active role in implementing adequate structures and processes for diagnostics and treatment of this patient group. It is argued that delirium (in dementia) can and should be regarded as a paradigm for a biopsychosocial disorder sui generis. In addition, aspects of the cl-psychiatrists role at two important interfaces of somatic and psychological medicine, i.e. primary care and emergency rooms, are highlighted. Finally, some information about the development of the professionalization of cl-psychiatry in Europe is given.

  16. Allergic to people: building bridges in a ripped psychic-soma.

    PubMed

    Teitelbaum, Stefanie

    2008-06-01

    An exploration of the use mind/body metaphors in a woman whose physical, environmental and psychoneurotic trauma culminated in an irreversible colostomy. She lived in a world of concrete symbols, her primary process damaged such that she could not create generative symbols to process her trauma. She regressed to a state of infantile megalomania, recoiling from the external reality of subjective others. Her introjective disorder mirrored her digestive disorder as she could absorb neither good objects nor good nutrients. The analytic situation has been an auxiliary fecal container and we work to bridge her mind body split with mind/body metaphors. As she reclaims lost development mastery, she displays a symbolized sphincter. As her capacity to form symbols grows, she rages and mourns for the loss of her fantasized ideal parents and her ideal body.

  17. Somatic embryogenesis from corolla tubes of interspecific amphiploids between cultivated sunflower (Helianthus annuus L.) and its wild species

    USDA-ARS?s Scientific Manuscript database

    Somatic embryogenesis in vitro provides an efficient means of plant multiplication, facilitating sunflower improvement and germplasm innovation. In the present study, using interspecific amphiploids (2n=4x=68) between cultivated sunflower and wild perennial Helianthus species as explant donors, soma...

  18. Comment on "Active sites for CO2 hydrogenation to methanol on Cu/ZnO catalysts".

    PubMed

    Nakamura, Junji; Fujitani, Tadahiro; Kuld, Sebastian; Helveg, Stig; Chorkendorff, Ib; Sehested, Jens

    2017-09-01

    Kattel et al (Reports, 24 March 2017, p. 1296) report that a zinc on copper (Zn/Cu) surface undergoes oxidation to zinc oxide/copper (ZnO/Cu) during carbon dioxide (CO 2 ) hydrogenation to methanol and conclude that the Cu-ZnO interface is the active site for methanol synthesis. Similar experiments conducted two decades ago by Fujitani and Nakamura et al demonstrated that Zn is attached to formate rather than being fully oxidized. Copyright © 2017, American Association for the Advancement of Science.

  19. Regulation of Survival by IKKE in Inflammatory Breast Cancer Involves EpCAM

    DTIC Science & Technology

    2014-07-01

    myeloproliferative neoplasms . Blood 115, 5232-5240 (2010). 28. J. S. Duncan, M. C. Whittle, K. Nakamura, A. N. Abell, A. A. Midland, J. S. Zawistowski, N. L...McCoon, Z. A. Cao, H. Yu, R. Jove, M. Zinda, The JAK2 inhibitor AZD1480 potently blocks Stat3 signaling and oncogenesis in solid tumors. Cancer cell...L. Richardson, T. Nikolskaya, Y. Nikolsky, X. S. Liu, D. E. Root, W. C. Hahn, D. A. Frank, K. Polyak, The JAK2 /STAT3 signaling pathway is required

  20. Heterogeneity of the Axon Initial Segment in Interneurons and Pyramidal Cells of Rodent Visual Cortex

    PubMed Central

    Höfflin, Felix; Jack, Alexander; Riedel, Christian; Mack-Bucher, Julia; Roos, Johannes; Corcelli, Corinna; Schultz, Christian; Wahle, Petra; Engelhardt, Maren

    2017-01-01

    The microdomain that orchestrates action potential initiation in neurons is the axon initial segment (AIS). It has long been considered to be a rather homogeneous domain at the very proximal axon hillock with relatively stable length, particularly in cortical pyramidal cells. However, studies in other brain regions paint a different picture. In hippocampal CA1, up to 50% of axons emerge from basal dendrites. Further, in about 30% of thick-tufted layer V pyramidal neurons in rat somatosensory cortex, axons have a dendritic origin. Consequently, the AIS is separated from the soma. Recent in vitro and in vivo studies have shown that cellular excitability is a function of AIS length/position and somatodendritic morphology, undermining a potentially significant impact of AIS heterogeneity for neuronal function. We therefore investigated neocortical axon morphology and AIS composition, hypothesizing that the initial observation of seemingly homogeneous AIS is inadequate and needs to take into account neuronal cell types. Here, we biolistically transfected cortical neurons in organotypic cultures to visualize the entire neuron and classify cell types in combination with immunolabeling against AIS markers. Using confocal microscopy and morphometric analysis, we investigated axon origin, AIS position, length, diameter as well as distance to the soma. We find a substantial AIS heterogeneity in visual cortical neurons, classified into three groups: (I) axons with somatic origin with proximal AIS at the axon hillock; (II) axons with somatic origin with distal AIS, with a discernible gap between the AIS and the soma; and (III) axons with dendritic origin (axon-carrying dendrite cell, AcD cell) and an AIS either starting directly at the axon origin or more distal to that point. Pyramidal cells have significantly longer AIS than interneurons. Interneurons with vertical columnar axonal projections have significantly more distal AIS locations than all other cells with their

  1. SASS Applied to Optimum Work Roll Profile Selection in the Hot Rolling of Wide Steel

    NASA Astrophysics Data System (ADS)

    Nolle, Lars

    The quality of steel strip produced in a wide strip rolling mill depends heavily on the careful selection of initial ground work roll profiles for each of the mill stands in the finishing train. In the past, these profiles were determined by human experts, based on their knowledge and experience. In previous work, the profiles were successfully optimised using a self-organising migration algorithm (SOMA). In this research, SASS, a novel heuristic optimisation algorithm that has only one control parameter, has been used to find the optimum profiles for a simulated rolling mill. The resulting strip quality produced using the profiles found by SASS is compared with results from previous work and the quality produced using the original profile specifications. The best set of profiles found by SASS clearly outperformed the original set and performed equally well as SOMA without the need of finding a suitable set of control parameters.

  2. Neuron Morphology Influences Axon Initial Segment Plasticity.

    PubMed

    Gulledge, Allan T; Bravo, Jaime J

    2016-01-01

    In most vertebrate neurons, action potentials are initiated in the axon initial segment (AIS), a specialized region of the axon containing a high density of voltage-gated sodium and potassium channels. It has recently been proposed that neurons use plasticity of AIS length and/or location to regulate their intrinsic excitability. Here we quantify the impact of neuron morphology on AIS plasticity using computational models of simplified and realistic somatodendritic morphologies. In small neurons (e.g., dentate granule neurons), excitability was highest when the AIS was of intermediate length and located adjacent to the soma. Conversely, neurons having larger dendritic trees (e.g., pyramidal neurons) were most excitable when the AIS was longer and/or located away from the soma. For any given somatodendritic morphology, increasing dendritic membrane capacitance and/or conductance favored a longer and more distally located AIS. Overall, changes to AIS length, with corresponding changes in total sodium conductance, were far more effective in regulating neuron excitability than were changes in AIS location, while dendritic capacitance had a larger impact on AIS performance than did dendritic conductance. The somatodendritic influence on AIS performance reflects modest soma-to-AIS voltage attenuation combined with neuron size-dependent changes in AIS input resistance, effective membrane time constant, and isolation from somatodendritic capacitance. We conclude that the impact of AIS plasticity on neuron excitability will depend largely on somatodendritic morphology, and that, in some neurons, a shorter or more distally located AIS may promote, rather than limit, action potential generation.

  3. Oscillating PDF in termini of circadian pacemaker neurons and synchronous molecular clocks in downstream neurons are not sufficient for sustenance of activity rhythms in constant darkness.

    PubMed

    Prakash, Pavitra; Nambiar, Aishwarya; Sheeba, Vasu

    2017-01-01

    In Drosophila, neuropeptide Pigment Dispersing Factor (PDF) is expressed in small and large ventral Lateral Neurons (sLNv and lLNv), among which sLNv are critical for activity rhythms in constant darkness. Studies show that this is mediated by rhythmic accumulation and likely secretion of PDF from sLNv dorsal projections, which in turn synchronises molecular oscillations in downstream circadian neurons. Using targeted expression of a neurodegenerative protein Huntingtin in LNv, we evoke a selective loss of neuropeptide PDF and clock protein PERIOD from sLNv soma. However, PDF is not lost from sLNv dorsal projections and lLNv. These flies are behaviourally arrhythmic in constant darkness despite persistence of PDF oscillations in sLNv dorsal projections and synchronous PERIOD oscillations in downstream circadian neurons. We find that PDF oscillations in sLNv dorsal projections are not sufficient for sustenance of activity rhythms in constant darkness and this is suggestive of an additional component that is possibly dependent on sLNv molecular clock and PDF in sLNv soma. Additionally, despite loss of PERIOD in sLNv, their activity rhythms entrain to light/dark cycles indicating that sLNv molecular clocks are not necessary for entrainment. Under constant light, these flies lack PDF from both soma and dorsal projections of sLNv, and when subjected to light/dark cycles, show morning and evening anticipation and accurately phased morning and evening peaks. Thus, under light/dark cycles, PDF in sLNv is not necessary for morning anticipation.

  4. Oscillating PDF in termini of circadian pacemaker neurons and synchronous molecular clocks in downstream neurons are not sufficient for sustenance of activity rhythms in constant darkness

    PubMed Central

    Prakash, Pavitra; Nambiar, Aishwarya; Sheeba, Vasu

    2017-01-01

    In Drosophila, neuropeptide Pigment Dispersing Factor (PDF) is expressed in small and large ventral Lateral Neurons (sLNv and lLNv), among which sLNv are critical for activity rhythms in constant darkness. Studies show that this is mediated by rhythmic accumulation and likely secretion of PDF from sLNv dorsal projections, which in turn synchronises molecular oscillations in downstream circadian neurons. Using targeted expression of a neurodegenerative protein Huntingtin in LNv, we evoke a selective loss of neuropeptide PDF and clock protein PERIOD from sLNv soma. However, PDF is not lost from sLNv dorsal projections and lLNv. These flies are behaviourally arrhythmic in constant darkness despite persistence of PDF oscillations in sLNv dorsal projections and synchronous PERIOD oscillations in downstream circadian neurons. We find that PDF oscillations in sLNv dorsal projections are not sufficient for sustenance of activity rhythms in constant darkness and this is suggestive of an additional component that is possibly dependent on sLNv molecular clock and PDF in sLNv soma. Additionally, despite loss of PERIOD in sLNv, their activity rhythms entrain to light/dark cycles indicating that sLNv molecular clocks are not necessary for entrainment. Under constant light, these flies lack PDF from both soma and dorsal projections of sLNv, and when subjected to light/dark cycles, show morning and evening anticipation and accurately phased morning and evening peaks. Thus, under light/dark cycles, PDF in sLNv is not necessary for morning anticipation. PMID:28558035

  5. The subcellular distribution of T-type Ca2+ channels in interneurons of the lateral geniculate nucleus.

    PubMed

    Allken, Vaneeda; Chepkoech, Joy-Loi; Einevoll, Gaute T; Halnes, Geir

    2014-01-01

    Inhibitory interneurons (INs) in the lateral geniculate nucleus (LGN) provide both axonal and dendritic GABA output to thalamocortical relay cells (TCs). Distal parts of the IN dendrites often enter into complex arrangements known as triadic synapses, where the IN dendrite plays a dual role as postsynaptic to retinal input and presynaptic to TC dendrites. Dendritic GABA release can be triggered by retinal input, in a highly localized process that is functionally isolated from the soma, but can also be triggered by somatically elicited Ca(2+)-spikes and possibly by backpropagating action potentials. Ca(2+)-spikes in INs are predominantly mediated by T-type Ca(2+)-channels (T-channels). Due to the complex nature of the dendritic signalling, the function of the IN is likely to depend critically on how T-channels are distributed over the somatodendritic membrane (T-distribution). To study the relationship between the T-distribution and several IN response properties, we here run a series of simulations where we vary the T-distribution in a multicompartmental IN model with a realistic morphology. We find that the somatic response to somatic current injection is facilitated by a high T-channel density in the soma-region. Conversely, a high T-channel density in the distal dendritic region is found to facilitate dendritic signalling in both the outward direction (increases the response in distal dendrites to somatic input) and the inward direction (the soma responds stronger to distal synaptic input). The real T-distribution is likely to reflect a compromise between several neural functions, involving somatic response patterns and dendritic signalling.

  6. The Subcellular Distribution of T-Type Ca2+ Channels in Interneurons of the Lateral Geniculate Nucleus

    PubMed Central

    Allken, Vaneeda; Chepkoech, Joy-Loi; Einevoll, Gaute T.; Halnes, Geir

    2014-01-01

    Inhibitory interneurons (INs) in the lateral geniculate nucleus (LGN) provide both axonal and dendritic GABA output to thalamocortical relay cells (TCs). Distal parts of the IN dendrites often enter into complex arrangements known as triadic synapses, where the IN dendrite plays a dual role as postsynaptic to retinal input and presynaptic to TC dendrites. Dendritic GABA release can be triggered by retinal input, in a highly localized process that is functionally isolated from the soma, but can also be triggered by somatically elicited Ca2+-spikes and possibly by backpropagating action potentials. Ca2+-spikes in INs are predominantly mediated by T-type Ca2+-channels (T-channels). Due to the complex nature of the dendritic signalling, the function of the IN is likely to depend critically on how T-channels are distributed over the somatodendritic membrane (T-distribution). To study the relationship between the T-distribution and several IN response properties, we here run a series of simulations where we vary the T-distribution in a multicompartmental IN model with a realistic morphology. We find that the somatic response to somatic current injection is facilitated by a high T-channel density in the soma-region. Conversely, a high T-channel density in the distal dendritic region is found to facilitate dendritic signalling in both the outward direction (increases the response in distal dendrites to somatic input) and the inward direction (the soma responds stronger to distal synaptic input). The real T-distribution is likely to reflect a compromise between several neural functions, involving somatic response patterns and dendritic signalling. PMID:25268996

  7. Protection of Salivary Function by Concomitant Pilocarpine During Radiotherapy: A Double-Blind, Randomized, Placebo-Controlled Study

    DOE Office of Scientific and Technical Information (OSTI.GOV)

    Burlage, Fred R.; Roesink, Judith M.; Kampinga, Harm H.

    2008-01-01

    Purpose: To investigate the effect of concomitant administration of pilocarpine during radiotherapy for head-and-neck squamous cell carcinoma (HNSCC) on postradiotherapy xerostomia. Methods and Materials: A prospective, double blind, placebo-controlled randomized trial including 170 patients with HNSCC was executed to study the protective effect of pilocarpine on radiotherapy-induced parotid gland dysfunction. The primary objective endpoint was parotid flow rate complication probability (PFCP) scored 6 weeks, 6 months, and 12 months after radiotherapy. Secondary endpoints included Late Effects of Normal Tissue/Somatic Objective Management Analytic scale (LENT SOMA) and patient-rated xerostomia scores. For all parotid glands, dose-volume histograms were assessed because the dosemore » distribution in the parotid glands is considered the most important prognostic factor with regard to radiation-induced salivary dysfunction. Results: Although no significant differences in PFCP were found for the two treatments arms, a significant (p = 0.03) reduced loss of parotid flow 1 year after radiotherapy was observed in those patients who received pilocarpine and a mean parotid dose above 40 Gy. The LENT SOMA and patient-rated xerostomia scores showed similar trends toward less dryness-related complaints for the pilocarpine group. Conclusions: Concomitant administration of pilocarpine during radiotherapy did not improve the PFCP or LENT SOMA and patient-rated xerostomia scores. In a subgroup of patients with a mean dose above 40 Gy, pilocarpine administration resulted in sparing of parotid gland function. Therefore, pilocarpine could be provided to patients in whom sufficient sparing of the parotid is not achievable.« less

  8. Immunolocalization of vesicular glutamate transporters 1 and 2 in the rat inferior colliculus.

    PubMed

    Altschuler, R A; Tong, L; Holt, A G; Oliver, D L

    2008-06-12

    The inferior colliculus is a major relay nucleus in the ascending auditory pathways that receives multiple glutamatergic inputs. Vesicular glutamate transporters 1 and 2 (VGLUT1, VGLUT2) most often have complementary non-overlapping distributions and can be used to differentiate glutamatergic inputs. The present study therefore examined co-immunolabeling of VGLUT1 and VGLUT2 in three divisions of the rat inferior colliculus. Additional co-immunolabeling of microtubule-associated protein 2 and neuronal class III beta-tubulin provided visualization of neuronal soma and processes and allowed identification of axo-somatic versus axo-dendritic contacts. Results showed numerous VGLUT1 and 2 immunolabeled terminals in the central nucleus, lateral cortex and dorsal cortex. In all three divisions there was little to no co-containment of the two vesicular glutamate transporters indicating a complementary distribution. VGLUT1 made predominantly axo-dendritic connections in the neuropil, while VGLUT2 had many axo-somatic contacts in addition to axo-dendritic contacts. VGLUT2 immunolabeled terminals were numerous on the soma and proximal dendrites of many medium-to-large and large neurons in the central nucleus and medium to large neurons in the dorsal cortex. There were more VGLUT2 terminals than VGLUT1 in all divisions and more VGLUT2 terminals in dorsal and lateral cortices than in the central nucleus. This study shows that VGLUT1 and VGLUT2 differentiate complementary patterns of glutamatergic inputs into the central nucleus, lateral and dorsal cortex of the inferior colliculus with VGLUT1 endings predominantly on the dendrites and VGLUT2 on both dendrites and somas.

  9. Neuron Morphology Influences Axon Initial Segment Plasticity123

    PubMed Central

    2016-01-01

    In most vertebrate neurons, action potentials are initiated in the axon initial segment (AIS), a specialized region of the axon containing a high density of voltage-gated sodium and potassium channels. It has recently been proposed that neurons use plasticity of AIS length and/or location to regulate their intrinsic excitability. Here we quantify the impact of neuron morphology on AIS plasticity using computational models of simplified and realistic somatodendritic morphologies. In small neurons (e.g., dentate granule neurons), excitability was highest when the AIS was of intermediate length and located adjacent to the soma. Conversely, neurons having larger dendritic trees (e.g., pyramidal neurons) were most excitable when the AIS was longer and/or located away from the soma. For any given somatodendritic morphology, increasing dendritic membrane capacitance and/or conductance favored a longer and more distally located AIS. Overall, changes to AIS length, with corresponding changes in total sodium conductance, were far more effective in regulating neuron excitability than were changes in AIS location, while dendritic capacitance had a larger impact on AIS performance than did dendritic conductance. The somatodendritic influence on AIS performance reflects modest soma-to-AIS voltage attenuation combined with neuron size-dependent changes in AIS input resistance, effective membrane time constant, and isolation from somatodendritic capacitance. We conclude that the impact of AIS plasticity on neuron excitability will depend largely on somatodendritic morphology, and that, in some neurons, a shorter or more distally located AIS may promote, rather than limit, action potential generation. PMID:27022619

  10. Trends in the Northern-hemisphere Climatologies of Local Wave Activity and Fluxes in a Warming Climate

    NASA Astrophysics Data System (ADS)

    Huang, S. Y.; Nakamura, N.

    2016-12-01

    The finite-amplitude local wave activity (LWA) identifies both the locations and magnitudes of anomalous wave events (Huang and Nakamura 2016, JAS), which are often associated with extreme weather conditions such as heat waves and storms at the rim. Variance in LWA in synoptic timescale is well-explained by the wave activity flux variance (i.e. conservative dynamics), while beyond seasonal time scale, the convergence/divergence of wave activity flux is balanced by non-conservative processes (e.g. vertical fluxes of heat and momentum at the surface, mixing, radiative forcing etc.). Analysis of ERA-Interim data during 1979-2015 shows that there is generally an increasing trend in the vertically-integrated interior LWA in Northern Winter, except over Central Pacific and Southern Europe. There is, in contrast, a decreasing trend in LWA in Northern summer, except over the high-latitude oceanic regions and low-latitude continental regions. The trends in the wave activity flux convergence in both seasons are consistent with such observations in LWA except over the Atlantic sector. In this presentation, I will illustrate how the change in circulation in a warming climate is associated with change in spatial distribution and frequency of extreme weather events by comparing the change in wave activity flux vectors with the observed change in LWA climatology. I will also quantify the permanent effect of non-conservative processes in terms of decadal change in eddy-free reference states of zonal wind and temperature (Nakamura and Solomon 2011).

  11. The hobo transposable element has transposase-dependent and -independent excision activity in drosophilid species

    USDA-ARS?s Scientific Manuscript database

    Mobility of the hobo transposable element was determined for several strains of Drosophila melanogaster and several Drosophila species. Mobility was assessed by use of an in vivo transient assay in the soma of developing embryos, which monitored hobo excision from injected indicator plasmids. Excisi...

  12. Theoretical Study of Hydrogen Adsorption on the GaN(0001) Surface

    DTIC Science & Technology

    2004-06-01

    423 (1999) 70. [39] J.E. Northrup, J. Neugebauer, R.M. Feenstra, A.R. Smith, Phys. Rev. B 61 (2000) 9932. [40] K. Nakamura, T. Hayashi , A. Tachibana, K...Hasegawa, I.S.T. Tsong, T. Sakurai, T. Ohno , Phys. Rev. Lett. 82 (1999) 3074. [45] K. Raghavachari, Q. Fu, G. Chen, L. Li, C.H. Li, D.C. Law, R.F. Hicks, J...Xue, S. Kuwano, J.T. Sadowski, K.F. Kelly, T. Sakurai, T. Ohno , Phys. Rev. Lett. 84 (2000) 4015. [78] S. Vézian, F. Semond, J. Massies, D.W. Bullock, Z

  13. A Dermatologist's Ammunition in the War Against Smoking: A Photoaging App.

    PubMed

    Brinker, Titus Josef; Enk, Alexander; Gatzka, Martina; Nakamura, Yasuhiro; Sondermann, Wiebke; Omlor, Albert Joachim; Petri, Maximilian Philip; Karoglan, Ante; Seeger, Werner; Klode, Joachim; von Kalle, Christof; Schadendorf, Dirk

    2017-09-21

    This viewpoint reviews the perspectives for dermatology as a specialty to go beyond the substantial impact of smoking on skin disease and leverage the impact of skin changes on a person's self-concept and behavior in the design of effective interventions for smoking prevention and cessation. ©Titus Josef Brinker, Alexander Enk, Martina Gatzka, Yasuhiro Nakamura, Wiebke Sondermann, Albert Joachim Omlor, Maximilian Philip Petri, Ante Karoglan, Werner Seeger, Joachim Klode, Christof von Kalle, Dirk Schadendorf. Originally published in the Journal of Medical Internet Research (http://www.jmir.org), 21.09.2017.

  14. Optical Spectroscopy of TCP J04432130+4721280 (V392 Per) Confirms a Nova Eruption

    NASA Astrophysics Data System (ADS)

    Wagner, R. M.; Terndrup, D.; Darnley, M. J.; Starrfield, S.; Woodward, C. E.; Henze, M.

    2018-04-01

    Following reports of a new transient of magnitude 6.2 in Perseus on 2018 April 29.4740 UT discovered by Y. Nakamura designated TCP J04432130+4721280 (http://www.cbat.eps.harvard.edu/unconf/followups/J04432130+4721280.html) and positionally coincident with the previously known U Gem type dwarf nova V392 Per, we obtained an optical spectrum on 2018 April 30.116 UT (range: 396-687 nm; resolution 0.3 nm) with the 2.4 m Hiltner telescope (+OSMOS) of the MDM Observatory on Kitt Peak.

  15. Golgi study of medium spiny neurons from dorsolateral striatum of the turtle Trachemys scripta elegans.

    PubMed

    González, Carolina; Mendoza, Janeth; Avila-Costa, María Rosa; Arias, Juan M; Barral, Jaime

    2013-11-27

    Comparative anatomy has shown similarities between reptilian and mammalian basal ganglia. Here the morphological characteristics of the medium spiny neurons (MSN) in the dorsolateral striatum (DLS) of the turtle are described after staining them with the Golgi technique. The soma of MSN in DLS showed three main forms: spherical, ovoid, and fusiform. The number of primary dendritic branches (3-4 den-drites/cell) was less than observed in mammals. The MSN axon originates mainly from the soma, and randomly it emerges at the beginning of the primary dendrite. The main differences between turtle and mammalian MSN were detected on dendritic spines. Short, thin, bifurcated and fungiform types of den-dritic spines were observed in the turtle's MSN, according to their shape. In most of the analyzed spines,it was found that its length considerably exceeded that reported in mammals, with dendritic spines upto 8 μm in length. These differences could play an important role in the modulation of motor networks preserved along the vertebrate evolution.

  16. The large Maf factor Traffic Jam controls gonad morphogenesis in Drosophila.

    PubMed

    Li, Michelle A; Alls, Jeffrey D; Avancini, Rita M; Koo, Karen; Godt, Dorothea

    2003-11-01

    Interactions between somatic and germline cells are critical for the normal development of egg and sperm. Here we show that the gene traffic jam (tj) produces a soma-specific factor that controls gonad morphogenesis and is required for female and male fertility. tj encodes the only large Maf factor in Drosophila melanogaster, an orthologue of the atypical basic Leu zipper transcription factors c-Maf and MafB/Kreisler in vertebrates. Expression of tj occurs in somatic gonadal cells that are in direct contact with germline cells throughout development. In tj mutant gonads, somatic cells fail to inter-mingle and properly envelop germline cells, causing an early block in germ cell differentiation. In addition, tj mutant somatic cells show an increase in the level of expression for several adhesion molecules. We propose that tj is a critical modulator of the adhesive properties of somatic cells, facilitating germline-soma interactions that are essential for germ cell differentiation.

  17. Slice cultures of the imprinting-relevant forebrain area MNH of the domestic chick: quantitative characterization of neuronal morphology.

    PubMed

    Hofmann, H; Braun, K

    1995-05-26

    The persistence of morphological features of neurons in slice cultures of the imprinting-relevant forebrain area MNH (mediorostral neostriatum and hyperstriatum ventrale) of the domestic chick was analysed at 7, 14, 21 and 28 days in vitro. After having been explanted and kept in culture the neurons in vitro have larger soma areas, longer and more extensively branched dendritic trees and lower spine frequencies compared to the neurons in vivo. During the analyzed culturing period, the parameters soma area, total and mean dendritic length, number of dendrites, number of dendritic nodes per dendrite and per neuron as well as the spine densities in different dendritic segments showed no significant differences between early and late periods. Highly correlated in every age group were the total dendritic length and the number of dendritic nodes per neuron, indicating regular ramification during dendritic growth. Since these morphological parameters remain stable during the first 4 weeks in vitro, this culture system may provide a suitable model to investigate experimentally induced morphological changes.

  18. Myelinated sensory and alpha motor axon regeneration in peripheral nerve neuromas

    NASA Technical Reports Server (NTRS)

    Macias, M. Y.; Lehman, C. T.; Sanger, J. R.; Riley, D. A.

    1998-01-01

    Histochemical staining for carbonic anhydrase and cholinesterase (CE) activities was used to analyze sensory and motor axon regeneration, respectively, during neuroma formation in transected and tube-encapsulated peripheral nerves. Median-ulnar and sciatic nerves in the rodent model permitted testing whether a 4 cm greater distance of the motor neuron soma from axotomy site or intrinsic differences between motor and sensory neurons influenced regeneration and neuroma formation 10, 30, and 90 days later. Ventral root radiculotomy confirmed that CE-stained axons were 97% alpha motor axons. Distance significantly delayed axon regeneration. When distance was negligible, sensory axons grew out sooner than motor axons, but motor axons regenerated to a greater quantity. These results indicate regeneration differences between axon subtypes and suggest more extensive branching of motor axons within the neuroma. Thus, both distance from injury site to soma and inherent motor and sensory differences should be considered in peripheral nerve repair strategies.

  19. Structure of the germline genome of Tetrahymena thermophila and relationship to the massively rearranged somatic genome

    PubMed Central

    Hamilton, Eileen P; Kapusta, Aurélie; Huvos, Piroska E; Bidwell, Shelby L; Zafar, Nikhat; Tang, Haibao; Hadjithomas, Michalis; Krishnakumar, Vivek; Badger, Jonathan H; Caler, Elisabet V; Russ, Carsten; Zeng, Qiandong; Fan, Lin; Levin, Joshua Z; Shea, Terrance; Young, Sarah K; Hegarty, Ryan; Daza, Riza; Gujja, Sharvari; Wortman, Jennifer R; Birren, Bruce W; Nusbaum, Chad; Thomas, Jainy; Carey, Clayton M; Pritham, Ellen J; Feschotte, Cédric; Noto, Tomoko; Mochizuki, Kazufumi; Papazyan, Romeo; Taverna, Sean D; Dear, Paul H; Cassidy-Hanley, Donna M; Xiong, Jie; Miao, Wei; Orias, Eduardo; Coyne, Robert S

    2016-01-01

    The germline genome of the binucleated ciliate Tetrahymena thermophila undergoes programmed chromosome breakage and massive DNA elimination to generate the somatic genome. Here, we present a complete sequence assembly of the germline genome and analyze multiple features of its structure and its relationship to the somatic genome, shedding light on the mechanisms of genome rearrangement as well as the evolutionary history of this remarkable germline/soma differentiation. Our results strengthen the notion that a complex, dynamic, and ongoing interplay between mobile DNA elements and the host genome have shaped Tetrahymena chromosome structure, locally and globally. Non-standard outcomes of rearrangement events, including the generation of short-lived somatic chromosomes and excision of DNA interrupting protein-coding regions, may represent novel forms of developmental gene regulation. We also compare Tetrahymena’s germline/soma differentiation to that of other characterized ciliates, illustrating the wide diversity of adaptations that have occurred within this phylum. DOI: http://dx.doi.org/10.7554/eLife.19090.001 PMID:27892853

  20. Electrical Identification and Selective Microstimulation of Neuronal Compartments Based on Features of Extracellular Action Potentials

    NASA Astrophysics Data System (ADS)

    Radivojevic, Milos; Jäckel, David; Altermatt, Michael; Müller, Jan; Viswam, Vijay; Hierlemann, Andreas; Bakkum, Douglas J.

    2016-08-01

    A detailed, high-spatiotemporal-resolution characterization of neuronal responses to local electrical fields and the capability of precise extracellular microstimulation of selected neurons are pivotal for studying and manipulating neuronal activity and circuits in networks and for developing neural prosthetics. Here, we studied cultured neocortical neurons by using high-density microelectrode arrays and optical imaging, complemented by the patch-clamp technique, and with the aim to correlate morphological and electrical features of neuronal compartments with their responsiveness to extracellular stimulation. We developed strategies to electrically identify any neuron in the network, while subcellular spatial resolution recording of extracellular action potential (AP) traces enabled their assignment to the axon initial segment (AIS), axonal arbor and proximal somatodendritic compartments. Stimulation at the AIS required low voltages and provided immediate, selective and reliable neuronal activation, whereas stimulation at the soma required high voltages and produced delayed and unreliable responses. Subthreshold stimulation at the soma depolarized the somatic membrane potential without eliciting APs.

  1. Activity-dependent decrease in contact areas between subsurface cisterns and plasma membrane of hippocampal neurons.

    PubMed

    Tao-Cheng, Jung-Hwa

    2018-04-16

    Subsurface cistern (SSC) in neuronal soma and primary dendrites is a specialized compartment of endoplasmic reticulum (ER) that is in close apposition (10 nm) with the plasma membrane (PM). ER-PM contact areas are thought to be involved in intracellular calcium regulation. Here, structural changes of SSC in hippocampal neurons were examined by electron microscopy upon depolarization with high K + (90 mM) or application of NMDA (50 μM) in rat dissociated cultures as well as organotypic slice cultures. The number and average length of SSC-PM contact areas in neuronal somas significantly decreased within 30 s under excitatory condition. This decrease in SSC-PM contact area progressed with time and was reversible. These results demonstrate a structural decoupling between the SSC and the PM upon stimulation, suggesting that there may be a functional decoupling of the calcium regulation. Because SSC-PM contact areas may mediate calcium influx, the decrease in contact area may protect neurons from calcium overload upon heightened stimulation.

  2. EM connectomics reveals axonal target variation in a sequence-generating network

    PubMed Central

    Narayanan, Rajeevan T; Svara, Fabian; Egger, Robert; Oberlaender, Marcel; Denk, Winfried; Long, Michael A

    2017-01-01

    The sequential activation of neurons has been observed in various areas of the brain, but in no case is the underlying network structure well understood. Here we examined the circuit anatomy of zebra finch HVC, a cortical region that generates sequences underlying the temporal progression of the song. We combined serial block-face electron microscopy with light microscopy to determine the cell types targeted by HVC(RA) neurons, which control song timing. Close to their soma, axons almost exclusively targeted inhibitory interneurons, consistent with what had been found with electrical recordings from pairs of cells. Conversely, far from the soma the targets were mostly other excitatory neurons, about half of these being other HVC(RA) cells. Both observations are consistent with the notion that the neural sequences that pace the song are generated by global synaptic chains in HVC embedded within local inhibitory networks. DOI: http://dx.doi.org/10.7554/eLife.24364.001 PMID:28346140

  3. [Emotions and affect in psychoanalysisis].

    PubMed

    Carton, Solange; Widlöcher, Daniel

    2012-06-01

    The goal of this paper is to give some indications on the concept of affect in psychoanalysis. There is no single theory of affect, and Freud gave successive definitions, which continue to be deepened in contemporary psychoanalysis. We review some steps of Freud works on affect, then we look into some present major questions, such as its relationship to soma, the nature of unconscious affects and the repression of affect, which is particularly developed in the field of psychoanalytic psychosomatic. From Freud's definitions of affect as one of the drive representative and as a limit-concept between the somatic and the psychic, we develop some major theoretical perspectives, which give a central place to soma and drive impulses, and which agree on the major idea that affect is the result of a process. We then note some parallelism between psychoanalysis of affect and psychology and neurosciences of emotion, and underline the gaps and conditions of comparison between these different epistemological approaches.

  4. Male reproductive strategy and decreased longevity.

    PubMed

    Vinogradov, A E

    1998-06-01

    An explanation of the inter-gender difference in longevity consistent with the 'disposable soma' theory of ageing is proposed. It is based on the concept of r-K selection as applied to the inter-gender situation. The concept predicts that the gender with a higher potential reproductive rate (males) should invest relatively less in somatic maintenance, which in its turn should result in a lower longevity according to the 'disposable soma' theory of ageing. In females, which are interpreted as K-selected organisms, the reproductive strategy strongly depends on steady, secure constitution designed for oocyte/embryo bearing and is therefore closely related to somatic maintenance, whereas in (r-selected) males it has a greater behavioural component--risky, variable, with a greater potential productive success at the expense of somatic maintenance. The higher metabolic and growth rates, a higher premature mortality and a longer period of sexual competence of males also find explanation as a complex of r-selected traits.

  5. The developmental basis for germline mosaicism in mouse and Drosophila melanogaster.

    PubMed

    Drost, J B; Lee, W R

    1998-01-01

    Data involving germline mosaics in Drosophila melanogaster and mouse are reconciled with developmental observations. Mutations that become fixed in the early embryo before separation of soma from the germline may, by the sampling process of development, continue as part of germline and/or differentiate into any somatic tissue. The cuticle of adult D. melanogaster, because of segmental development, can be used to estimate the proportion of mutant nuclei in the early embryo, but most somatic tissues and the germlines of both species continue from samples too small to be representative of the early embryo. Because of the small sample of cells/nuclei that remain in the germline after separation of soma in both species, mosaic germlines have percentages of mutant cells that vary widely, with a mean of 50% and an unusual platykurtic, flat-topped distribution. While the sampling process leads to similar statistical results for both species, their patterns of development are very different. In D. melanogaster the first differentiation is the separation of soma from germline with the germline continuing from a sample of only two to four nuclei, whereas the adult cuticle is a representative sample of cleavage nuclei. The presence of mosaicism in D. melanogaster germline is independent of mosaicism in the eye, head, and thorax. This independence was used to determine that mutations can occur at any of the early embryonic cell divisions and still average 50% mutant germ cells when the germline is mosaic; however, the later the mutation occurs, the higher the proportion of completely nonmutant germlines. In contrast to D. melanogaster, the first differentiation in the mouse does not separate soma from germline but produces the inner cell mass that is representative of the cleavage nuclei. Following formation of the primitive streak, the primordial germ cells develop at the base of the allantois and among a clonally related sample of cells, providing the same statistical

  6. Transection of Preganglionic Axons Leads to CNS Neuronal Plasticity Followed by Survival and Target Reinnervation

    PubMed Central

    Coulibaly, Aminata P.; Gannon, Sean M.; Hawk, Kiel; Walsh, Brian F.; Isaacson, Lori G.

    2013-01-01

    The goals of the present study were to investigate the changes in sympathetic preganglionic neurons following transection of distal axons in the cervical sympathetic trunk (CST) that innervate the superior cervical ganglion (SCG) and to assess changes in the protein expression of brain derived neurotrophic factor (BDNF) and its receptor TrkB in the thoracic spinal cord. . At 1 week, a significant decrease in soma volume and reduced soma expression of choline acetyltransferase (ChAT) in the intermediolateral cell column (IML) of T1 spinal cord were observed, with both ChAT-ir and non-immunoreactive neurons expressing the injury marker activating transcription factor 3. . These changes were transient, and at later time points, ChAT expression and soma volume returned to control values and the number of ATF3 neurons declined. No evidence for cell loss or neuronal apoptosis was detected at any time point. Protein levels of BDNF and/or full length TrkB in the spinal cord were increased throughout the survival period. In the SCG, both ChAT-ir axons and ChAT protein remained decreased at 16 weeks, but were increased compared to the 10 week time point. These results suggest that though IML neurons show reduced ChAT expression and cell volume at 1 week following CST transection, at later time points, the neurons recovered and exhibited no significant signs of neurodegeneration. The alterations in BDNF and/or TrkB may have contributed to the survival of the IML neurons and the recovery of ChAT expression, as well as to the reinnervation of the SCG. PMID:23891533

  7. Analysis of gene expression from the Wolbachia genome of a filarial nematode supports both metabolic and defensive roles within the symbiosis

    PubMed Central

    Darby, Alistair C.; Armstrong, Stuart D.; Bah, Germanus S.; Kaur, Gaganjot; Hughes, Margaret A.; Kay, Suzanne M.; Koldkjær, Pia; Rainbow, Lucille; Radford, Alan D.; Blaxter, Mark L.; Tanya, Vincent N.; Trees, Alexander J.; Cordaux, Richard; Wastling, Jonathan M.; Makepeace, Benjamin L.

    2012-01-01

    The α-proteobacterium Wolbachia is probably the most prevalent, vertically transmitted symbiont on Earth. In contrast with its wide distribution in arthropods, Wolbachia is restricted to one family of animal-parasitic nematodes, the Onchocercidae. This includes filarial pathogens such as Onchocerca volvulus, the cause of human onchocerciasis, or river blindness. The symbiosis between filariae and Wolbachia is obligate, although the basis of this dependency is not fully understood. Previous studies suggested that Wolbachia may provision metabolites (e.g., haem, riboflavin, and nucleotides) and/or contribute to immune defense. Importantly, Wolbachia is restricted to somatic tissues in adult male worms, whereas females also harbor bacteria in the germline. We sought to characterize the nature of the symbiosis between Wolbachia and O. ochengi, a bovine parasite representing the closest relative of O. volvulus. First, we sequenced the complete genome of Wolbachia strain wOo, which revealed an inability to synthesize riboflavin de novo. Using RNA-seq, we also generated endobacterial transcriptomes from male soma and female germline. In the soma, transcripts for membrane transport and respiration were up-regulated, while the gonad exhibited enrichment for DNA replication and translation. The most abundant Wolbachia proteins, as determined by geLC-MS, included ligands for mammalian Toll-like receptors. Enzymes involved in nucleotide synthesis were dominant among metabolism-related proteins, whereas the haem biosynthetic pathway was poorly represented. We conclude that Wolbachia may have a mitochondrion-like function in the soma, generating ATP for its host. Moreover, the abundance of immunogenic proteins in wOo suggests a role in diverting the immune system toward an ineffective antibacterial response. PMID:22919073

  8. Spinal afferent neurons projecting to the rat lung and pleura express acid sensitive channels

    PubMed Central

    Groth, Michael; Helbig, Tanja; Grau, Veronika; Kummer, Wolfgang; Haberberger, Rainer V

    2006-01-01

    Background The acid sensitive ion channels TRPV1 (transient receptor potential vanilloid receptor-1) and ASIC3 (acid sensing ion channel-3) respond to tissue acidification in the range that occurs during painful conditions such as inflammation and ischemia. Here, we investigated to which extent they are expressed by rat dorsal root ganglion neurons projecting to lung and pleura, respectively. Methods The tracer DiI was either injected into the left lung or applied to the costal pleura. Retrogradely labelled dorsal root ganglion neurons were subjected to triple-labelling immunohistochemistry using antisera against TRPV1, ASIC3 and neurofilament 68 (marker for myelinated neurons), and their soma diameter was measured. Results Whereas 22% of pulmonary spinal afferents contained neither channel-immunoreactivity, at least one is expressed by 97% of pleural afferents. TRPV1+/ASIC3- neurons with probably slow conduction velocity (small soma, neurofilament 68-negative) were significantly more frequent among pleural (35%) than pulmonary afferents (20%). TRPV1+/ASIC3+ neurons amounted to 14 and 10% respectively. TRPV1-/ASIC3+ neurons made up between 44% (lung) and 48% (pleura) of neurons, and half of them presumably conducted in the A-fibre range (larger soma, neurofilament 68-positive). Conclusion Rat pleural and pulmonary spinal afferents express at least two different acid-sensitive channels that make them suitable to monitor tissue acidification. Patterns of co-expression and structural markers define neuronal subgroups that can be inferred to subserve different functions and may initiate specific reflex responses. The higher prevalence of TRPV1+/ASIC3- neurons among pleural afferents probably reflects the high sensitivity of the parietal pleura to painful stimuli. PMID:16813657

  9. Imaging and quantifying ganglion cells and other transparent neurons in the living human retina.

    PubMed

    Liu, Zhuolin; Kurokawa, Kazuhiro; Zhang, Furu; Lee, John J; Miller, Donald T

    2017-11-28

    Ganglion cells (GCs) are fundamental to retinal neural circuitry, processing photoreceptor signals for transmission to the brain via their axons. However, much remains unknown about their role in vision and their vulnerability to disease leading to blindness. A major bottleneck has been our inability to observe GCs and their degeneration in the living human eye. Despite two decades of development of optical technologies to image cells in the living human retina, GCs remain elusive due to their high optical translucency. Failure of conventional imaging-using predominately singly scattered light-to reveal GCs has led to a focus on multiply-scattered, fluorescence, two-photon, and phase imaging techniques to enhance GC contrast. Here, we show that singly scattered light actually carries substantial information that reveals GC somas, axons, and other retinal neurons and permits their quantitative analysis. We perform morphometry on GC layer somas, including projection of GCs onto photoreceptors and identification of the primary GC subtypes, even beneath nerve fibers. We obtained singly scattered images by: ( i ) marrying adaptive optics to optical coherence tomography to avoid optical blurring of the eye; ( ii ) performing 3D subcellular image registration to avoid motion blur; and ( iii ) using organelle motility inside somas as an intrinsic contrast agent. Moreover, through-focus imaging offers the potential to spatially map individual GCs to underlying amacrine, bipolar, horizontal, photoreceptor, and retinal pigment epithelium cells, thus exposing the anatomical substrate for neural processing of visual information. This imaging modality is also a tool for improving clinical diagnosis and assessing treatment of retinal disease. Copyright © 2017 the Author(s). Published by PNAS.

  10. The Possible Role of TASK Channels in Rank-Ordered Recruitment of Motoneurons in the Dorsolateral Part of the Trigeminal Motor Nucleus.

    PubMed

    Okamoto, Keiko; Emura, Norihito; Sato, Hajime; Fukatsu, Yuki; Saito, Mitsuru; Tanaka, Chie; Morita, Yukako; Nishimura, Kayo; Kuramoto, Eriko; Xu Yin, Dong; Furutani, Kazuharu; Okazawa, Makoto; Kurachi, Yoshihisa; Kaneko, Takeshi; Maeda, Yoshinobu; Yamashiro, Takashi; Takada, Kenji; Toyoda, Hiroki; Kang, Youngnam

    2016-01-01

    Because a rank-ordered recruitment of motor units occurs during isometric contraction of jaw-closing muscles, jaw-closing motoneurons (MNs) may be recruited in a manner dependent on their soma sizes or input resistances (IRs). In the dorsolateral part of the trigeminal motor nucleus (dl-TMN) in rats, MNs abundantly express TWIK (two-pore domain weak inwardly rectifying K channel)-related acid-sensitive-K(+) channel (TASK)-1 and TASK3 channels, which determine the IR and resting membrane potential. Here we examined how TASK channels are involved in IR-dependent activation/recruitment of MNs in the rat dl-TMN by using multiple methods. The real-time PCR study revealed that single large MNs (>35 μm) expressed TASK1 and TASK3 mRNAs more abundantly compared with single small MNs (15-20 μm). The immunohistochemistry revealed that TASK1 and TASK3 channels were complementarily distributed in somata and dendrites of MNs, respectively. The density of TASK1 channels seemed to increase with a decrease in soma diameter while there were inverse relationships between the soma size of MNs and IR, resting membrane potential, or spike threshold. Dual whole-cell recordings obtained from smaller and larger MNs revealed that the recruitment of MNs depends on their IRs in response to repetitive stimulation of the presumed Ia afferents. 8-Bromoguanosine-cGMP decreased IRs in small MNs, while it hardly changed those in large MNs, and subsequently decreased the difference in spike-onset latency between the smaller and larger MNs, causing a synchronous activation of MNs. These results suggest that TASK channels play critical roles in rank-ordered recruitment of MNs in the dl-TMN.

  11. Drawing together psyche, soma and spirit: my career in cultural psychiatry.

    PubMed

    Dein, Simon

    2011-04-01

    In this article I discuss my career in cultural psychiatry. I begin by examining the influence of my personal background on my interests in cultural psychiatry and religion and health. I then discuss my research, which has focused upon two areas: the cognitive and phenomenological parallels between religious experiences and psychopathological states, and relationships between biomedicine and religious healing in diverse cultural contexts. Finally, I discuss plans for future research and teaching.

  12. The Effects of Rational and Irrational Self-Verbalizations on Performance Efficiency and Levels of Anxiety.

    ERIC Educational Resources Information Center

    Rosin, Lindsay; Nelson, W. M. III

    1983-01-01

    Investigated effects of rational vs. irrational belief systems and rational vs. irrational self-verbalizations on anxiety and persistence. Subjects (N=40) were instructed to assemble a virtually insolvable task called Soma, and were assigned to either a rational or irrational self-talk condition. Rational self-talk subjects showed a significant…

  13. Departures from the Friedmann-Lemaitre-Robertston-Walker Cosmological Model in an Inhomogeneous Universe: A Numerical Examination.

    PubMed

    Giblin, John T; Mertens, James B; Starkman, Glenn D

    2016-06-24

    While the use of numerical general relativity for modeling astrophysical phenomena and compact objects is commonplace, the application to cosmological scenarios is only just beginning. Here, we examine the expansion of a spacetime using the Baumgarte-Shapiro-Shibata-Nakamura formalism of numerical relativity in synchronous gauge. This work represents the first numerical cosmological study that is fully relativistic, nonlinear, and without symmetry. The universe that emerges exhibits an average Friedmann-Lemaître-Robertson-Walker (FLRW) behavior; however, this universe also exhibits locally inhomogeneous expansion beyond that expected in linear perturbation theory around a FLRW background.

  14. Optogenetic approaches to characterize the long-range synaptic pathways from the hypothalamus to brain stem autonomic nuclei

    PubMed Central

    Piñol, Ramón A.; Bateman, Ryan; Mendelowitz, David

    2012-01-01

    Recent advances in optogenetic methods demonstrate the feasibility of selective photoactivation at the soma of neurons that express channelrhodopsin-2 (ChR2), but a comprehensive evaluation of different methods to selectively evoke transmitter release from distant synapses using optogenetic approaches is needed. Here we compared different lentiviral vectors, with sub-population-specific and strong promoters, and transgenic methods to express and photostimulate ChR2 in the long-range projections of paraventricular nucleus of the hypothalamus (PVN) neurons to brain stem cardiac vagal neurons (CVNs). Using PVN subpopulation-specific promoters for vasopressin and oxytocin, we were able to depolarize the soma of these neurons upon photostimulation, but these promoters were not strong enough to drive sufficient expression for optogenetic stimulation and synaptic release from the distal axons. However, utilizing the synapsin promoter photostimulation of distal PVN axons successfully evoked glutamatergic excitatory post-synaptic currents in CVNs. Employing the Cre/loxP system, using the Sim-1 Cre-driver mouse line, we found that the Rosa-CAG-LSL-ChR2-EYFP Cre-responder mice expressed higher levels of ChR2 than the Rosa-CAG-LSL-ChR2-tdTomato line in the PVN, judged by photo-evoked currents at the soma. However, neither was able to drive sufficient expression to observe and photostimulate the long-range projections to brainstem autonomic regions. We conclude that a viral vector approach with a strong promoter is required for successful optogenetic stimulation of distal axons to evoke transmitter release in pre-autonomic PVN neurons. This approach can be very useful to study important hypothalamus-brainstem connections, and can be easily modified to selectively activate other long-range projections within the brain. PMID:22890236

  15. String method for calculation of minimum free-energy paths in Cartesian space in freely-tumbling systems.

    PubMed

    Branduardi, Davide; Faraldo-Gómez, José D

    2013-09-10

    The string method is a molecular-simulation technique that aims to calculate the minimum free-energy path of a chemical reaction or conformational transition, in the space of a pre-defined set of reaction coordinates that is typically highly dimensional. Any descriptor may be used as a reaction coordinate, but arguably the Cartesian coordinates of the atoms involved are the most unprejudiced and intuitive choice. Cartesian coordinates, however, present a non-trivial problem, in that they are not invariant to rigid-body molecular rotations and translations, which ideally ought to be unrestricted in the simulations. To overcome this difficulty, we reformulate the framework of the string method to integrate an on-the-fly structural-alignment algorithm. This approach, referred to as SOMA (String method with Optimal Molecular Alignment), enables the use of Cartesian reaction coordinates in freely tumbling molecular systems. In addition, this scheme permits the dissection of the free-energy change along the most probable path into individual atomic contributions, thus revealing the dominant mechanism of the simulated process. This detailed analysis also provides a physically-meaningful criterion to coarse-grain the representation of the path. To demonstrate the accuracy of the method we analyze the isomerization of the alanine dipeptide in vacuum and the chair-to-inverted-chair transition of β -D mannose in explicit water. Notwithstanding the simplicity of these systems, the SOMA approach reveals novel insights into the atomic mechanism of these isomerizations. In both cases, we find that the dynamics and the energetics of these processes are controlled by interactions involving only a handful of atoms in each molecule. Consistent with this result, we show that a coarse-grained SOMA calculation defined in terms of these subsets of atoms yields nearidentical minimum free-energy paths and committor distributions to those obtained via a highly-dimensional string.

  16. String method for calculation of minimum free-energy paths in Cartesian space in freely-tumbling systems

    PubMed Central

    Branduardi, Davide; Faraldo-Gómez, José D.

    2014-01-01

    The string method is a molecular-simulation technique that aims to calculate the minimum free-energy path of a chemical reaction or conformational transition, in the space of a pre-defined set of reaction coordinates that is typically highly dimensional. Any descriptor may be used as a reaction coordinate, but arguably the Cartesian coordinates of the atoms involved are the most unprejudiced and intuitive choice. Cartesian coordinates, however, present a non-trivial problem, in that they are not invariant to rigid-body molecular rotations and translations, which ideally ought to be unrestricted in the simulations. To overcome this difficulty, we reformulate the framework of the string method to integrate an on-the-fly structural-alignment algorithm. This approach, referred to as SOMA (String method with Optimal Molecular Alignment), enables the use of Cartesian reaction coordinates in freely tumbling molecular systems. In addition, this scheme permits the dissection of the free-energy change along the most probable path into individual atomic contributions, thus revealing the dominant mechanism of the simulated process. This detailed analysis also provides a physically-meaningful criterion to coarse-grain the representation of the path. To demonstrate the accuracy of the method we analyze the isomerization of the alanine dipeptide in vacuum and the chair-to-inverted-chair transition of β-D mannose in explicit water. Notwithstanding the simplicity of these systems, the SOMA approach reveals novel insights into the atomic mechanism of these isomerizations. In both cases, we find that the dynamics and the energetics of these processes are controlled by interactions involving only a handful of atoms in each molecule. Consistent with this result, we show that a coarse-grained SOMA calculation defined in terms of these subsets of atoms yields nearidentical minimum free-energy paths and committor distributions to those obtained via a highly-dimensional string. PMID

  17. Change in and Long-Term Investigation of Neuro-Otologic Disorders in Disaster-Stricken Fukushima Prefecture: Retrospective Cohort Study before and after the Great East Japan Earthquake

    PubMed Central

    Kuriyama, Shinichi; Obara, Taku; Hashimoto, Ken; Tateda, Yutaka; Okumura, Yuri; Kobayashi, Toshimitsu; Katori, Yukio

    2015-01-01

    On March 11, 2011, Japan’s northeast Pacific coast was hit by a gigantic earthquake and subsequent tsunami. Soma City in Fukushima Prefecture is situated approximately 44 km north of Fukushima Daiichi Nuclear Power Plant. Soma General Hospital is the only hospital in Soma City that provides full-time otolaryngological medical care. We investigated the changes in new patients from one year before to three years after the disaster. We investigated 18,167 new patients treated at our department during the four years from April 1, 2010 to March 31, 2014. Of the new patients, we categorized the diagnoses into Meniere’s disease, acute low-tone sensorineural hearing loss, vertigo, sudden deafness, tinnitus, and facial palsy as neuro-otologic symptoms. We also investigated the changes in the numbers of patients whom we examined at that time concerning other otolaryngological disorders, including epistaxis, infectious diseases of the laryngopharynx, and allergic rhinitis. The total number of new patients did not change remarkably on a year-to-year basis. Conversely, cases of vertigo, Meniere’s disease, and acute low-tone sensorineural hearing loss increased in number immediately after the disaster, reaching a plateau in the second year and slightly decreasing in the third year. Specifically, 4.8% of patients suffering from these neuro-otologic diseases had complications from depression and other mental diseases. With regard to new patients in our department, there was no apparent increase in the number of patients suffering from diseases other than neuro-otologic diseases, including epistaxis, and allergic rhinitis. Patients suffering from vertigo and/or dizziness increased during the first few years after the disaster. These results are attributed to the continuing stress and tension of the inhabitants. This investigation of those living in the disaster area highlights the need for long-term support. PMID:25849607

  18. Mechanism of orientation of stimulating currents in magnetic brain stimulation (abstract)

    NASA Astrophysics Data System (ADS)

    Ueno, S.; Matsuda, T.

    1991-04-01

    We made a functional map of the human motor cortex related to the hand and foot areas by stimulating the human brain with a focused magnetic pulse. We observed that each functional area in the cortex has an optimum direction for which stimulating currents can produce neural excitation. The present report focuses on the mechanism which is responsible for producing this anisotropic response to brain stimulation. We first obtained a functional map of the brain related to the left ADM (abductor digiti minimi muscles). When the stimulating currents were aligned in the direction from the left to the right hemisphere, clear EMG (electromyographic) responses were obtained only from the left ADM to magnetic stimulation of both hemisphere. When the stimulating currents were aligned in the direction from the right to the left hemisphere, clear EMG signals were obtained only from the right ADM to magnetic stimulation of both hemisphere. The functional maps of the brain were sensitive to changes in the direction of the stimulating currents. To explain the phenomena obtained in the experiments, we developed a model of neural excitation elicited by magnetic stimulation. When eddy currents which are induced by pulsed magnetic fields flow in the direction from soma to the distal part of neural fiber, depolarized area in the distal part are excited, and the membrane excitation propagates along the nerve fiber. In contrast, when the induced currents flow in the direction from the distal part to soma, hyperpolarized parts block or inhibit neural excitation even if the depolarized parts near the soma can be excited. The model explains our observation that the orientation of the induced current vectors reflect both the functional and anatomical organization of the neural fibers in the brain.

  19. DOE Office of Scientific and Technical Information (OSTI.GOV)

    Karayigit, A.I.; Bulut, Y.; Karayigit, G.

    A total of 48 samples, feed coals (FCs), fly ashes (FAs) and bottom ashes (BAs), which were systematically collected once a week over an eight-week period from boiler units, B1-4 with 660 MW and B5-6 with 330 MW capacity from Soma power plant, have been evaluated for major and trace elements (Al, Ca, Fe, K, Mg, Mn, Na, Ti, S, As, B, Ba, Be, Bi, Cd, Co, Cr, Cu, Cs, Ga, Ge, Hf, Hg, Li, Mo, Nb, Ni, P, Pb, Rb, Sb, Sc, Se, Sn, Sr, Ta, Th, Tl, U, V, Y, Zn, Zr, and REEs) to get information onmore » behavior during coal combustion. This study indicates that some elements such as Hg, Bi, Cd, As, Pb, Ge, Tl, Sn, Zn, Sb, B show enrichments in FAs relative to the BAs in both group boiler units. In addition to these, Cs, Lu, Tm, and Ga in Units B1-4 and S in Units B5-6 also have enrichments in FAs. Elements showing enrichments in BAs in both group boiler units are Ta, Mn, Nb. In addition to these, Se, Ca, Mg, Na, Fe in Units B1-4 and Cu in Units B5-6 also have enrichments in BAs. The remaining elements investigated in this study have no clear segregation between FAs and BAs. Mass balance calculations with the two methods show that some elements, S, Ta, Hg, Se, Zn, Na, Ca in Units B1-4, and Hg, S, Ta, Se, P in Units B5-6, have volatile behavior during coal combustion in the Soma power plant. This study also implies that some elements, Sb and Tb in Units B1-4 and Sb in Units B5-6, have relatively high retention effects in the combustion residues from the Soma power plant.« less

  20. Cochlear microphonic broad tuning curves

    NASA Astrophysics Data System (ADS)

    Ayat, Mohammad; Teal, Paul D.; Searchfield, Grant D.; Razali, Najwani

    2015-12-01

    It is known that the cochlear microphonic voltage exhibits much broader tuning than does the basilar membrane motion. The most commonly used explanation for this is that when an electrode is inserted at a particular point inside the scala media, the microphonic potentials of neighbouring hair cells have different phases, leading to cancelation at the electrodes location. In situ recording of functioning outer hair cells (OHCs) for investigating this hypothesis is exceptionally difficult. Therefore, to investigate the discrepancy between the tuning curves of the basilar membrane and those of the cochlear microphonic, and the effect of phase cancellation of adjacent hair cells on the broadness of the cochlear microphonic tuning curves, we use an electromechanical model of the cochlea to devise an experiment. We explore the effect of adjacent hair cells (i.e., longitudinal phase cancellation) on the broadness of the cochlear microphonic tuning curves in different locations. The results of the experiment indicate that active longitudinal coupling (i.e., coupling with active adjacent outer hair cells) only slightly changes the broadness of the CM tuning curves. The results also demonstrate that there is a π phase difference between the potentials produced by the hair bundle and the soma near the place associated with the characteristic frequency based on place-frequency maps (i.e., the best place). We suggest that the transversal phase cancellation (caused by the phase difference between the hair bundle and the soma) plays a far more important role than longitudinal phase cancellation in the broadness of the cochlear microphonic tuning curves. Moreover, by increasing the modelled longitudinal resistance resulting the cochlear microphonic curves exhibiting sharper tuning. The results of the simulations suggest that the passive network of the organ of Corti determines the phase difference between the hair bundle and soma, and hence determines the sharpness of the

  1. Spatial separation of two different pathways accounting for the generation of calcium signals in astrocytes.

    PubMed

    Oschmann, Franziska; Mergenthaler, Konstantin; Jungnickel, Evelyn; Obermayer, Klaus

    2017-02-01

    Astrocytes integrate and process synaptic information and exhibit calcium (Ca2+) signals in response to incoming information from neighboring synapses. The generation of Ca2+ signals is mostly attributed to Ca2+ release from internal Ca2+ stores evoked by an elevated metabotropic glutamate receptor (mGluR) activity. Different experimental results associated the generation of Ca2+ signals to the activity of the glutamate transporter (GluT). The GluT itself does not influence the intracellular Ca2+ concentration, but it indirectly activates Ca2+ entry over the membrane. A closer look into Ca2+ signaling in different astrocytic compartments revealed a spatial separation of those two pathways. Ca2+ signals in the soma are mainly generated by Ca2+ release from internal Ca2+ stores (mGluR-dependent pathway). In astrocytic compartments close to the synapse most Ca2+ signals are evoked by Ca2+ entry over the plasma membrane (GluT-dependent pathway). This assumption is supported by the finding, that the volume ratio between the internal Ca2+ store and the intracellular space decreases from the soma towards the synapse. We extended a model for mGluR-dependent Ca2+ signals in astrocytes with the GluT-dependent pathway. Additionally, we included the volume ratio between the internal Ca2+ store and the intracellular compartment into the model in order to analyze Ca2+ signals either in the soma or close to the synapse. Our model results confirm the spatial separation of the mGluR- and GluT-dependent pathways along the astrocytic process. The model allows to study the binary Ca2+ response during a block of either of both pathways. Moreover, the model contributes to a better understanding of the impact of channel densities on the interaction of both pathways and on the Ca2+ signal.

  2. Mechanisms and distribution of ion channels in retinal ganglion cells: using temperature as an independent variable.

    PubMed

    Fohlmeister, Jürgen F; Cohen, Ethan D; Newman, Eric A

    2010-03-01

    Trains of action potentials of rat and cat retinal ganglion cells (RGCs) were recorded intracellularly across a temperature range of 7-37 degrees C. Phase plots of the experimental impulse trains were precision fit using multicompartment simulations of anatomically reconstructed rat and cat RGCs. Action potential excitation was simulated with a "Five-channel model" [Na, K(delayed rectifier), Ca, K(A), and K(Ca-activated) channels] and the nonspace-clamped condition of the whole cell recording was exploited to determine the channels' distribution on the dendrites, soma, and proximal axon. At each temperature, optimal phase-plot fits for RGCs occurred with the same unique channel distribution. The "waveform" of the electrotonic current was found to be temperature dependent, which reflected the shape changes in the experimental action potentials and confirmed the channel distributions. The distributions are cell-type specific and adequate for soma and dendritic excitation with a safety margin. The highest Na-channel density was found on an axonal segment some 50-130 microm distal to the soma, as determined from the temperature-dependent "initial segment-somadendritic (IS-SD) break." The voltage dependence of the gating rate constants remains invariant between 7 and 23 degrees C and between 30 and 37 degrees C, but undergoes a transition between 23 and 30 degrees C. Both gating-kinetic and ion-permeability Q10s remain virtually constant between 23 and 37 degrees C (kinetic Q10s = 1.9-1.95; permeability Q10s = 1.49-1.64). The Q10s systematically increase for T <23 degrees C (kinetic Q10 = 8 at T = 8 degrees C). The Na channels were consistently "sleepy" (non-Arrhenius) for T <8 degrees C, with a loss of spiking for T <7 degrees C.

  3. Selective control of cortical axonal spikes by a slowly inactivating K+ current

    PubMed Central

    Shu, Yousheng; Yu, Yuguo; Yang, Jing; McCormick, David A.

    2007-01-01

    Neurons are flexible electrophysiological entities in which the distribution and properties of ionic channels control their behaviors. Through simultaneous somatic and axonal whole-cell recording of layer 5 pyramidal cells, we demonstrate a remarkable differential expression of slowly inactivating K+ currents. Depolarizing the axon, but not the soma, rapidly activated a low-threshold, slowly inactivating, outward current that was potently blocked by low doses of 4-aminopyridine, α-dendrotoxin, and rTityustoxin-Kα. Block of this slowly inactivating current caused a large increase in spike duration in the axon but only a small increase in the soma and could result in distal axons generating repetitive discharge in response to local current injection. Importantly, this current was also responsible for slow changes in the axonal spike duration that are observed after somatic membrane potential change. These data indicate that low-threshold, slowly inactivating K+ currents, containing Kv1.2 α subunits, play a key role in the flexible properties of intracortical axons and may contribute significantly to intracortical processing. PMID:17581873

  4. Golgi Study of Medium Spiny Neurons from Dorsolateral Striatum of the Turtle Trachemys scripta elegans.

    PubMed

    González, Carolina; Mendoza, Janeth; Avila-Costa, María Rosa; Arias, Juan M; Barral, Jaime

    2013-10-25

    Comparative anatomy has shown similarities between reptilian and mammalian basal ganglia. Here the morphological characteristics of the medium spiny neurons (MSN) in the dorsolateral striatum (DLS) of the turtle are described after staining them with the Golgi technique. The soma of MSN in DLS showed three main forms: spherical, ovoid, and fusiform. The number of primary dendritic branches (3-4 dendrites/cell) was less than observed in mammals. The MSN axon originates mainly from the soma, and randomly it emerges at the beginning of the primary dendrite. The main differences between turtle and mammalian MSN were detected on dendritic spines. Short, thin, bifurcated and fungiform types of dendritic spines were observed in the turtle's MSN, according to their shape. In most of the analyzed spines, it was found that its length considerably exceeded that reported in mammals, with dendritic spines up to 8μm in length. These differences could play an important role in the modulation of motor networks preserved along the vertebrate evolution. Copyright © 2013. Published by Elsevier Ireland Ltd.

  5. The spine neck filters membrane potentials.

    PubMed

    Araya, Roberto; Jiang, Jiang; Eisenthal, Kenneth B; Yuste, Rafael

    2006-11-21

    Dendritic spines receive most synaptic inputs in the forebrain. Their morphology, with a spine head isolated from the dendrite by a slender neck, indicates a potential role in isolating inputs. Indeed, biochemical compartmentalization occurs at spine heads because of the diffusional bottleneck created by the spine neck. Here we investigate whether the spine neck also isolates inputs electrically. Using two-photon uncaging of glutamate on spine heads from mouse layer-5 neocortical pyramidal cells, we find that the amplitude of uncaging potentials at the soma is inversely proportional to neck length. This effect is strong and independent of the position of the spine in the dendritic tree and size of the spine head. Moreover, spines with long necks are electrically silent at the soma, although their heads are activated by the uncaging event, as determined with calcium imaging. Finally, second harmonic measurements of membrane potential reveal an attenuation of somatic voltages into the spine head, an attenuation directly proportional to neck length. We conclude that the spine neck plays an electrical role in the transmission of membrane potentials, isolating synapses electrically.

  6. The spine neck filters membrane potentials

    PubMed Central

    Araya, Roberto; Jiang, Jiang; Eisenthal, Kenneth B.; Yuste, Rafael

    2006-01-01

    Dendritic spines receive most synaptic inputs in the forebrain. Their morphology, with a spine head isolated from the dendrite by a slender neck, indicates a potential role in isolating inputs. Indeed, biochemical compartmentalization occurs at spine heads because of the diffusional bottleneck created by the spine neck. Here we investigate whether the spine neck also isolates inputs electrically. Using two-photon uncaging of glutamate on spine heads from mouse layer-5 neocortical pyramidal cells, we find that the amplitude of uncaging potentials at the soma is inversely proportional to neck length. This effect is strong and independent of the position of the spine in the dendritic tree and size of the spine head. Moreover, spines with long necks are electrically silent at the soma, although their heads are activated by the uncaging event, as determined with calcium imaging. Finally, second harmonic measurements of membrane potential reveal an attenuation of somatic voltages into the spine head, an attenuation directly proportional to neck length. We conclude that the spine neck plays an electrical role in the transmission of membrane potentials, isolating synapses electrically. PMID:17093040

  7. Psychosomatics: a current overview.

    PubMed

    Fischbein, José Eduardo

    2011-02-01

    The term 'psychosomatic' has typically defined a series of illnesses in which somatic injury breaks out from psychic conflict not recognized as such. Currently, health is considered the only psychosomatic state of integration of mind and soma: an ideal state of integration. Somatic pathology is an effect of mind/body splitting. In the heterogeneous 'field of psychosomatics' interaction between psyche and soma ranges from classical psychosomatic illness to sporadic episodes in which the body has responded to an inability to process mental conflict. The author briefly reviews the development of psychoanalytic thought on psychosomatics in Argentina. He suggests the need to find appropriate conceptual tools to approach the mental structure underlying this pathology. He presents his ideas about the mental functioning of patients with somatization disorders. He introduces the concept of somatic event as a restitution phenomenon through which the subject attempts to re-establish self-integration and links with reality. He also offers some reflections on temporality and on changes in psychoanalytic technique with these patients. A clinical case illustrates his ideas. Copyright © 2011 Institute of Psychoanalysis.

  8. Characterization of postsynaptic calcium signals in the pyramidal neurons of anterior cingulate cortex

    PubMed Central

    Li, Xu-Hui; Song, Qian; Chen, Tao; Zhuo, Min

    2017-01-01

    Calcium signaling is critical for synaptic transmission and plasticity. N-methyl-D-aspartic acid (NMDA) receptors play a key role in synaptic potentiation in the anterior cingulate cortex. Most previous studies of calcium signaling focus on hippocampal neurons, little is known about the activity-induced calcium signals in the anterior cingulate cortex. In the present study, we show that NMDA receptor-mediated postsynaptic calcium signals induced by different synaptic stimulation in anterior cingulate cortex pyramidal neurons. Single and multi-action potentials evoked significant suprathreshold Ca2+ increases in somas and spines. Both NMDA receptors and voltage-gated calcium channels contributed to this increase. Postsynaptic Ca2+signals were induced by puff-application of glutamate, and a NMDA receptor antagonist AP5 blocked these signals in both somas and spines. Finally, long-term potentiation inducing protocols triggered postsynaptic Ca2+ influx, and these influx were NMDA receptor dependent. Our results provide the first study of calcium signals in the anterior cingulate cortex and demonstrate that NMDA receptors play important roles in postsynaptic calcium signals in anterior cingulate cortex pyramidal neurons. PMID:28726541

  9. Cell Type–Specific Three-Dimensional Structure of Thalamocortical Circuits in a Column of Rat Vibrissal Cortex

    PubMed Central

    de Kock, Christiaan P. J.; Bruno, Randy M.; Ramirez, Alejandro; Meyer, Hanno S.; Dercksen, Vincent J.; Helmstaedter, Moritz; Sakmann, Bert

    2012-01-01

    Soma location, dendrite morphology, and synaptic innervation may represent key determinants of functional responses of individual neurons, such as sensory-evoked spiking. Here, we reconstruct the 3D circuits formed by thalamocortical afferents from the lemniscal pathway and excitatory neurons of an anatomically defined cortical column in rat vibrissal cortex. We objectively classify 9 cortical cell types and estimate the number and distribution of their somata, dendrites, and thalamocortical synapses. Somata and dendrites of most cell types intermingle, while thalamocortical connectivity depends strongly upon the cell type and the 3D soma location of the postsynaptic neuron. Correlating dendrite morphology and thalamocortical connectivity to functional responses revealed that the lemniscal afferents can account for some of the cell type- and location-specific subthreshold and spiking responses after passive whisker touch (e.g., in layer 4, but not for other cell types, e.g., in layer 5). Our data provides a quantitative 3D prediction of the cell type–specific lemniscal synaptic wiring diagram and elucidates structure–function relationships of this physiologically relevant pathway at single-cell resolution. PMID:22089425

  10. Action potential-independent and pharmacologically unique vesicular serotonin release from dendrites

    PubMed Central

    Colgan, Lesley A.; Cavolo, Samantha L.; Commons, Kathryn G.; Levitan, Edwin S.

    2012-01-01

    Serotonin released within the dorsal raphe nucleus (DR) induces feedback inhibition of serotonin neuron activity and consequently regulates mood-controlling serotonin release throughout the forebrain. Serotonin packaged in vesicles is released in response to action potentials by the serotonin neuron soma and terminals, but the potential for release by dendrites is unknown. Here three-photon (3P) microscopy imaging of endogenous serotonin in living rat brain slice, immunofluorescence and immuno-gold electron microscopy detection of VMAT2 (vesicular monoamine transporter 2) establish the presence of vesicular serotonin within DR dendrites. Furthermore, activation of glutamate receptors is shown to induce vesicular serotonin release from dendrites. However, unlike release from the soma and terminals, dendritic serotonin release is independent of action potentials, relies on L-type Ca2+ channels, is induced preferentially by NMDA, and displays distinct sensitivity to the selective serotonin reuptake inhibitor (SSRI) antidepressant fluoxetine. The unique control of dendritic serotonin release has important implications for DR physiology and the antidepressant action of SSRIs, dihydropyridines and NMDA receptor antagonists. PMID:23136413

  11. Flight Control Requirements for Weapon Delivery. Volume 1. Development of the Terminal Aerial Weapon Delivery Simulation (TAWDS) Programs and Their Use in Formulating Flying Qualities Guidelines for Manually Coupled Aircraft Weapon Delivery Systems

    DTIC Science & Technology

    1976-03-01

    Altitudo Abow TKi«f (ft) Tar|«tAt SüLiVil TartatiiatSomaAltituda Abow Soa Laval Bomb Ground Rania (ft) Altitudt Abow SwLawl (ft) Bomb Ground... Rania (ft) Error in Bomb Ground (Un|« No Pj/Po (ft) (mils) (ft) (mite) 400 500 500 400 400 400 1000 1000 2000 3000 4000 5000 5.109

  12. Medical Surveillance Technology - Clinical Looking Glass

    DTIC Science & Technology

    2012-10-01

    0016 5c. PROGRAM ELEMENT NUMBER 6. AUTHOR(S) 5d. PROJECT NUMBER Ms Susan Mia McCroskey, Mr. Noah Geberer , Dr. Eran Bellin 5e. TASK NUMBER...Chowdhury, Soma 0-40% Edwards, Richie 25-30% Geberer , Noah 60-70% Golden, Joe 15-30% Lee, William 0-15% McCroskey, Mia 29-50% Muresan, Mircea 0

  13. List of participants at SIDE IV meeting, Tokyo, 27 November--1 December 2000

    NASA Astrophysics Data System (ADS)

    2001-12-01

    Mark J Ablowitz, Vsevolod Adler, Mark Alber, Said Belmehdi, Marco Boiti, Claude Brezinski, R Bullough, Y M Chiang, Theodore Chihara, Peter A Clarkson, Robert Conte, Adam Doliwa, Vladimir Dorodnitsyn, Mitsuaki Eguchi, Claire Gilson, Basil Grammaticos, Valeri Gromak, Rod Halburd, Koji Hasegawa, Jarmo Hietarinta, Ryogo Hirota, Xing Biao Hu, M Idzumi, J Inoguchi, Hiroya Ishikara, Mourad Ismail, Shin Isojima, Kenichi Ito, Yoshiaki Itoh, Masashi Iwasaki, Klara Janglajew, Michio Jimbo, Nalini Joshi, Kenji Kajiwara, Saburo Kakei, Masaru Kamata, Satoshi Kamei, Rinat Kashaev, Shingo Kawai, Taeko Kimijima, K Kimura, Anatol Kirillov, Koichi Kondo, Boris Konopelchenko, Martin Kruskal, Atsuo Kuniba, Wataru Kunishima, Franklin Lambert, Serguei Leble, Decio Levi, Shigeru Maeda, Manuel Manas, Ken-Ichi Maruno, Tetsu Masuda, J Matsukidaira, Atsushi Matsumiya, Shigeki Matsutani, Yukitaka Minesaki, Mikio Murata, Micheline Musette, Atsushi Nagai, Katsuya Nakagawa, Atsushi Nakamula, Akira Nakamura, Yoshimasa Nakamura, Frank Nijhoff, J J C Nimmo, Katsuhiro Nishinari, Michitomo Nishizawa, A Nobe, Masatoshi Noumi, Yaeko Ohsaki, Yasuhiro Ohta, Kazuo Okamoto, Alexandre Orlov, Naoki Osada, Flora Pempinelli, Spiro Pyrlis, Reinout Quispel, Orlando Ragnisco, Alfred Ramani, Jean-Pierre Ramis, Andreas Ruffing, Simon Ruijsenaars, Satoru Saito, Noriko Saitoh, Hidetaka Sakai, Paulo Santini, Narimasa Sasa, Ryu Sasaki, Yoshikatsu Sasaki, Junkichi Satsuma, Sergei Sergeev, Nobuhiko Shinzawa, Evgueni Sklyanin, Juris Suris, Norio Suzuki, Yukiko Tagami, Katsuaki Takahashi, Daisuke Takahashi, Tomoyuki Takenawa, Yoshiro Takeyama, K M Tamizhmani, T Tamizhmani, Kouichi Toda, Morikatsu Toda, Tetsuji Tokihiro, Takayuki Tsuchida, Yohei Tsuchiya, Teruhisa Tsuda, Satoru Tsujimoto, Walter Van Assche, Claude Viallet, Luc Vinet, Shinsuke Watanabe, Yoshihida Watanabe, Ralph Willox, Pavel Winternitz, Yasuhiko Yamada, Yuji Yamada, Jin Yoneda, Haruo Yoshida, Katsuhiko Yoshida, Daisuke Yoshihara, Fumitaka Yura, J

  14. Continuous H/V spectral ratio analysis of ambient noise: a necessity to understand microzonation results obtained by mobile stations

    NASA Astrophysics Data System (ADS)

    Van Noten, Koen; Lecocq, Thomas

    2016-04-01

    Estimating the resonance frequency (f0) and amplification factor of unconsolidated sediments by H/V spectral ratio (HVSR) analysis of seismic ambient noise has been widely used since Nakamura's proposal in 1989. To measure f0 properly, Nakamura suggested to perform microzonation surveys at night when the artificial microtremor is small and does not fully disrupt the ambient seismic noise. As nightly fieldwork is not always a reasonable demand, we propose an alternative workflow of Nakamura's technique to improve the quality of HVSR results obtained by ambient noise measurements of mobile stations during the day. This new workflow includes the automated H/V calculation of continuous seismic data of a stationary or permanent station installed near the microzonation site for as long as the survey lasts in order to control the error in the HVSR analysis obtained by the mobile stations. In this presentation, we apply this workflow on one year of seismic data at two different case studies; i.e. a rural site with a shallow bedrock depth of 30 m and an urban site (Brussels, capital of Belgium, bedrock depth of 110 m) where human activity is continuous 24h/day. By means of an automated python script, the fundamental peak frequency and the H/V amplitude are automatically picked from H/V spectra that are calculated from 50% overlapping, 30 minute windows during the whole year. Afterwards, the f0 and amplitude picks are averaged per hour/per day for the whole year. In both case studies, the H/V amplitude and the fundamental frequencies range considerable, up to ˜15% difference between the daily and nightly measurements. As bedrock depth is known from boreholes at both sites, we concluded that the nightly picked f0 is the true one. Our results thus suggest that changes in the determined f0 and H/V amplitude are dominantly caused by the human behaviour which is stored in the ambient seismic noise (e.g. later onset of traffic in a weekend, quiet Sundays, differences between

  15. Input Source and Strength Influences Overall Firing Phase of Model Hippocampal CA1 Pyramidal Cells During Theta: Relevance to REM Sleep Reactivation and Memory Consolidation

    PubMed Central

    Booth, Victoria; Poe, Gina R.

    2005-01-01

    In simulation studies using a realistic model CA1 pyramidal cell, we accounted for the shift in mean firing phase from theta cycle peaks to theta cycle troughs during REM sleep reactivation of hippocampal CA1 place cells over several days of growing familiarization with an environment (Poe et al., 2000). Changes in the theta drive between proximal and distal dendritic regions of the cell modulated the theta phase of firing when stimuli were presented at proximal and distal dendritic locations. Stimuli at proximal dendritic sites (proximal to 100 μm from the soma) invoked firing with a significant phase preference at the depolarizing theta peaks, while distal stimuli (> 290 μm from the soma) invoked firing at hyperpolarizing theta troughs. The location-related phase preference depended on active dendritic conductances, a sufficient electrotonic separation between input sites and theta-induced subthreshold membrane potential oscillations in the cell. The simulation results predict that the shift in mean theta phase during REM sleep cellular reactivation could occur through potentiation of distal dendritic (temporo-ammonic) synapses and depotentiation of proximal dendritic (Schaffer collateral) synapses over the course of familiarization. PMID:16411243

  16. Small RNA-Mediated trans-Nuclear and trans-Element Communications in Tetrahymena DNA Elimination.

    PubMed

    Noto, Tomoko; Mochizuki, Kazufumi

    2018-06-18

    Epigenetic inheritance of acquired traits is widespread among eukaryotes, but how and to what extent such information is transgenerationally inherited is still unclear. The patterns of programmed DNA elimination in ciliates are epigenetically and transgenerationally inherited, and it has been proposed that small RNAs, which shuttle between the germline and the soma, regulate this epigenetic inheritance. In this study, we test the existence and role of such small-RNA-mediated communication by epigenetically disturbing the pattern of DNA elimination in Tetrahymena. We show that the pattern of DNA elimination is, indeed, determined by the selective turnover of small RNAs, which is induced by the interaction between germline-derived small RNAs and the somatic genome. In addition, we show that DNA elimination of an element is regulated by small-RNA-mediated communication with other eliminated elements. By contrast, no evidence obtained thus far supports the notion that transfer of epigenetic information from the soma to the germline, if any, regulates DNA elimination. Our results indicate that small-RNA-mediated trans-nuclear and trans-element communication, in addition to unknown information in the germline genome, contributes to determining the pattern of DNA elimination. Copyright © 2018 Elsevier Ltd. All rights reserved.

  17. Vesicle capture, not delivery, scales up neuropeptide storage in neuroendocrine terminals.

    PubMed

    Bulgari, Dinara; Zhou, Chaoming; Hewes, Randall S; Deitcher, David L; Levitan, Edwin S

    2014-03-04

    Neurons vary in their capacity to produce, store, and release neuropeptides packaged in dense-core vesicles (DCVs). Specifically, neurons used for cotransmission have terminals that contain few DCVs and many small synaptic vesicles, whereas neuroendocrine neuron terminals contain many DCVs. Although the mechanistic basis for presynaptic variation is unknown, past research demonstrated transcriptional control of neuropeptide synthesis suggesting that supply from the soma limits presynaptic neuropeptide accumulation. Here neuropeptide release is shown to scale with presynaptic neuropeptide stores in identified Drosophila cotransmitting and neuroendocrine terminals. However, the dramatic difference in DCV number in these terminals occurs with similar anterograde axonal transport and DCV half-lives. Thus, differences in presynaptic neuropeptide stores are not explained by DCV delivery from the soma or turnover. Instead, greater neuropeptide accumulation in neuroendocrine terminals is promoted by dramatically more efficient presynaptic DCV capture. Greater capture comes with tradeoffs, however, as fewer uncaptured DCVs are available to populate distal boutons and replenish neuropeptide stores following release. Finally, expression of the Dimmed transcription factor in cotransmitting neurons increases presynaptic DCV capture. Therefore, DCV capture in the terminal is genetically controlled and determines neuron-specific variation in peptidergic function.

  18. Vesicle capture, not delivery, scales up neuropeptide storage in neuroendocrine terminals

    PubMed Central

    Bulgari, Dinara; Zhou, Chaoming; Hewes, Randall S.; Deitcher, David L.; Levitan, Edwin S.

    2014-01-01

    Neurons vary in their capacity to produce, store, and release neuropeptides packaged in dense-core vesicles (DCVs). Specifically, neurons used for cotransmission have terminals that contain few DCVs and many small synaptic vesicles, whereas neuroendocrine neuron terminals contain many DCVs. Although the mechanistic basis for presynaptic variation is unknown, past research demonstrated transcriptional control of neuropeptide synthesis suggesting that supply from the soma limits presynaptic neuropeptide accumulation. Here neuropeptide release is shown to scale with presynaptic neuropeptide stores in identified Drosophila cotransmitting and neuroendocrine terminals. However, the dramatic difference in DCV number in these terminals occurs with similar anterograde axonal transport and DCV half-lives. Thus, differences in presynaptic neuropeptide stores are not explained by DCV delivery from the soma or turnover. Instead, greater neuropeptide accumulation in neuroendocrine terminals is promoted by dramatically more efficient presynaptic DCV capture. Greater capture comes with tradeoffs, however, as fewer uncaptured DCVs are available to populate distal boutons and replenish neuropeptide stores following release. Finally, expression of the Dimmed transcription factor in cotransmitting neurons increases presynaptic DCV capture. Therefore, DCV capture in the terminal is genetically controlled and determines neuron-specific variation in peptidergic function. PMID:24550480

  19. Statistical study of biomechanics of living brain cells during growth and maturation on artificial substrates.

    PubMed

    Chen, La; Li, Wenfang; Maybeck, Vanessa; Offenhäusser, Andreas; Krause, Hans-Joachim

    2016-11-01

    There is increasing evidence that mechanical issues play a vital role in neuron growth and brain development. The importance of this grows as novel devices, whose material properties differ from cells, are increasingly implanted in the body. In this work, we studied the mechanical properties of rat brain cells over time and on different materials by using a high throughput magnetic tweezers system. It was found that the elastic moduli of both neurite and soma in networked neurons increased with growth. However, neurites at DIV4 exhibited a relatively high stiffness, which could be ascribed to the high outgrowth tension. The power-law exponents (viscoelasticity) of both neurites and somas of neurons decreased with culture time. On the other hand, the stiffness of glial cells also increased with maturity. Furthermore, both neurites and glia become softer when cultured on compliant substrates. Especially, the glial cells cultured on a soft substrate obviously showed a less dense and more porous actin and GFAP mesh. In addition, the viscoelasticity of both neurites and glia did not show a significant dependence on the substrates' stiffness. Copyright © 2016 Elsevier Ltd. All rights reserved.

  20. In Vitro Analysis of the Role of Schwann Cells on Axonal Degeneration and Regeneration Using Sensory Neurons from Dorsal Root Ganglia.

    PubMed

    López-Leal, Rodrigo; Diaz, Paula; Court, Felipe A

    2018-01-01

    Sensory neurons from dorsal root ganglion efficiently regenerate after peripheral nerve injuries. These neurons are widely used as a model system to study degenerative mechanisms of the soma and axons, as well as regenerative axonal growth in the peripheral nervous system. This chapter describes techniques associated to the study of axonal degeneration and regeneration using explant cultures of dorsal root ganglion sensory neurons in vitro in the presence or absence of Schwann cells. Schwann cells are extremely important due to their involvement in tissue clearance during axonal degeneration as well as their known pro-regenerative effect during regeneration in the peripheral nervous system. We describe methods to induce and study axonal degeneration triggered by axotomy (mechanical separation of the axon from its soma) and treatment with vinblastine (which blocks axonal transport), which constitute clinically relevant mechanical and toxic models of axonal degeneration. In addition, we describe three different methods to evaluate axonal regeneration using quantitative methods. These protocols constitute a valuable tool to analyze in vitro mechanisms associated to axonal degeneration and regeneration of sensory neurons and the role of Schwann cells in these processes.

  1. Thalamic reticular cells firing modes and its dependency on the frequency and amplitude ranges of the current stimulus.

    PubMed

    Hernandez, Oscar; Hernandez, Lilibeth; Vera, David; Santander, Alcides; Zurek, Eduardo

    2015-01-01

    The neurons of the Thalamic Reticular Nucleus (TRNn) respond to inputs in two activity modes called burst and tonic firing and both can be observed in different physiological states. The functional states of the thalamus depend in part on the properties of synaptic transmission between the TRNn and the thalamocortical and corticothalamic neurons. A dendrite can receive inhibitory and excitatory postsynaptic potentials. The novelties presented in this paper can be summarized as follows: First, it shows, through a computational simulation, that the burst and tonic firings observed in the TRNn soma could be explained as a product of random synaptic inputs on the distal dendrites, the tonic firings are generated by random excitatory stimuli, and the burst firings are generated by two different types of stimuli: inhibitory random stimuli, and a combination of inhibitory (from TRNn) and excitatory (from corticothalamic and thalamocortical neurons) random stimuli; second, according to in vivo recordings, we have found that the burst observed in the TRNn soma has graduate properties that are proportional to the stimuli frequency; and third, a novel method for showing in a quantitative manner the accelerando-decelerando pattern is proposed.

  2. Dehydroepiandrosterone and Dehydroepiandrosterone Sulfate: Anabolic, Neuroprotective, and Neuroexcitatory Properties in Military Men

    DTIC Science & Technology

    2013-01-01

    in olfactory bulbectomized mice. J Neurochem 2011; 117(5); 879-91. 14. Gubba EM Fawcett JW, Herbert J; The effects of corticosterone and...Newman AE, MacDougall-Shackleton SA, An YS, Kriengwatana B. Soma KK: Corticosterone and dehydroepiandrosterone have opposing effects on adult...supports nerve cell proliferation), and salivary alpha amylase (sAA; a proxy of sympathetic nervous system function). Separate regression analyses were

  3. Crystal Structures of Copper-depleted and Copper-bound Fungal Pro-tyrosinase

    PubMed Central

    Fujieda, Nobutaka; Yabuta, Shintaro; Ikeda, Takuya; Oyama, Takuji; Muraki, Norifumi; Kurisu, Genji; Itoh, Shinobu

    2013-01-01

    Tyrosinase, a dinuclear copper monooxygenase/oxidase, plays a crucial role in the melanin pigment biosynthesis. The structure and functions of tyrosinase have so far been studied extensively, but the post-translational maturation process from the pro-form to the active form has been less explored. In this study, we provide the crystal structures of Aspergillus oryzae full-length pro-tyrosinase in the holo- and the apo-forms at 1.39 and 2.05 Å resolution, respectively, revealing that Phe513 on the C-terminal domain is accommodated in the substrate-binding site as a substrate analog to protect the dicopper active site from substrate access (proteolytic cleavage of the C-terminal domain or deformation of the C-terminal domain by acid treatment transforms the pro-tyrosinase to the active enzyme (Fujieda, N., Murata, M., Yabuta, S., Ikeda, T., Shimokawa, C., Nakamura, Y., Hata, Y., and Itoh, S. (2012) ChemBioChem. 13, 193–201 and Fujieda, N., Murata, M., Yabuta, S., Ikeda, T., Shimokawa, C., Nakamura, Y., Hata, Yl, and Itoh, S. (2013) J. Biol. Inorg. Chem. 18, 19–26). Detailed crystallographic analysis and structure-based mutational studies have shown that the copper incorporation into the active site is governed by three cysteines as follows: Cys92, which is covalently bound to His94 via an unusual thioether linkage in the holo-form, and Cys522 and Cys525 of the CXXC motif located on the C-terminal domain. Molecular mechanisms of the maturation processes of fungal tyrosinase involving the accommodation of the dinuclear copper unit, the post-translational His-Cys thioether cross-linkage formation, and the proteolytic C-terminal cleavage to produce the active tyrosinase have been discussed on the basis of the detailed structural information. PMID:23749993

  4. Shallow Subsurface Velocity Structure using the Ambient Noise for the Garhwal and Kumaon Himalaya.

    NASA Astrophysics Data System (ADS)

    LAL, S.; Joshi, A.; S.; P.

    2017-12-01

    Abstract: In this paper effort has been made to obtain one dimensional subsurface velocity structure using H/V spectral ratio method Nakamura (1989). The complete study shows that ambient noises are reflective of structural properties of underlying strata. Data has been obtained at stations from foothills of Himalaya up to higher Himalaya along road using strong motion accelerograph in the Garhwal and Kumaon Himalaya along the two transects lines. Noise data has been processed using the seismosignal software. The ratio between the Fourier amplitude spectra of the horizontal components to the vertical component of the ambient noise had been used to consider the site effects of the concerned site. The relation given by Lermo and Chavez-Garcia (1993) between the thickness of layer and average S- wave velocity of the sedimentary layer has been utilized to obtain sub surface velocity model. To fit the synthetic H/V curve with the observed H/V curve, technique given by Castellaro and Mulargia (2009) is used in the present study. This model is improved via forward modelling to give final one dimensional velocity structure at a particular station. Velocity structures obtained at all stations are used to obtain continuous velocity models for concerned area using Kringing interpolation, which is correlated with the geology and tectonic of region. Keywords: Ambient noise, H/V spectral ratio, Site characterization, Accelerograph, Velocity ReferencesNakamura Y (1989). A method for dynamic characteristics estimation of subsurface using microtremor on the ground surface. QR RTRI 30(1):25-30. Castellaro S, Mulargia F (2009). The effect of velocity inversions on H/V. PAGEOPH 166:567-592. Lermo, J., & Chavez-Garcia, F. J. (1993). Site effect evaluation using spectral ratios with only one station Bulletin Seismological Society of America, 83, 1574-1594.

  5. Hyperbaric Oxygen Therapy for Radiation-Induced Cystitis and Proctitis

    DOE Office of Scientific and Technical Information (OSTI.GOV)

    Oliai, Caspian; Fisher, Brandon; Jani, Ashish

    Purpose: To provide a retrospective analysis of the efficacy of hyperbaric oxygen therapy (HBOT) for treating hemorrhagic cystitis (HC) and proctitis secondary to pelvic- and prostate-only radiotherapy. Methods and Materials: Nineteen patients were treated with HBOT for radiation-induced HC and proctitis. The median age at treatment was 66 years (range, 15-84 years). The range of external-beam radiation delivered was 50.0-75.6 Gy. Bleeding must have been refractory to other therapies. Patients received 100% oxygen at 2.0 atmospheres absolute pressure for 90-120 min per treatment in a monoplace chamber. Symptoms were retrospectively scored according to the Late Effects of Normal Tissues-Subjective, Objective,more » Management, Analytic (LENT-SOMA) scale to evaluate short-term efficacy. Recurrence of hematuria/hematochezia was used to assess long-term efficacy. Results: Four of the 19 patients were lost to follow-up. Fifteen patients were evaluated and received a mean of 29.8 dives: 11 developed HC and 4 proctitis. All patients experienced a reduction in their LENT-SOMA score. After completion of HBOT, the mean LENT-SOMA score was reduced from 0.78 to 0.20 in patients with HC and from 0.66 to 0.26 in patients with proctitis. Median follow-up was 39 months (range, 7-70 months). No cases of hematuria were refractory to HBOT. Complete resolution of hematuria was seen in 81% (n = 9) and partial response in 18% (n = 2). Recurrence of hematuria occurred in 36% (n = 4) after a median of 10 months. Complete resolution of hematochezia was seen in 50% (n = 2), partial response in 25% (n = 1), and refractory bleeding in 25% (n = 1). Conclusions: Hyperbaric oxygen therapy is appropriate for radiation-induced HC once less time-consuming therapies have failed to resolve the bleeding. In these conditions, HBOT is efficacious in the short and long term, with minimal side effects.« less

  6. Thermal and quantum fluctuations of confined Bose–Einstein condensate beyond the Bogoliubov approximation

    DOE Office of Scientific and Technical Information (OSTI.GOV)

    Nakamura, Y., E-mail: yusuke.n@asagi.waseda.jp; Nagano Prefectural Kiso Seiho High School, Nagano 397-8571; Kawaguchi, T., E-mail: pionelish30@toki.waseda.jp

    The formulation for zero mode of a Bose–Einstein condensate beyond the Bogoliubov approximation at zero temperature [Y. Nakamura et al., Phys. Rev. A 89 (2014) 013613] is extended to finite temperature. Both thermal and quantum fluctuations are considered in a manner consistent with a concept of spontaneous symmetry breakdown for a finite-size system. Therefore, we need a proper treatment of the zero mode operators, which invoke non-trivial enhancements in depletion condensate and thermodynamical quantities such as the specific heat. The enhancements are visible in the weak interaction case. Our approach reproduces the results of a homogeneous system in the Bogoliubovmore » approximation in a large particle number limit.« less

  7. Spectroscopic Confirmation of TCP J07134590-2112330 as a Galactic Classical Nova in Canis Major

    NASA Astrophysics Data System (ADS)

    Strader, Jay; Chomiuk, Laura; Bahramian, Arash; Swihart, Sam

    2018-03-01

    TCP J07134590-2112330 was discovered by Yuji Nakamura on 2018 March 24.5 UT as a 12 mag optical transient. We obtained spectroscopic observations of TCP J07134590-2112330 with the Goodman spectrograph on the 4-m SOAR telescope on 2018 Mar 25.1 UT, with a low-resolution spectrum (R 1200) covering 3850-7850 A. The spectrum indicates that TCP J07134590-2112330 is a young classical nova, with strong hydrogen Balmer emission lines and additional strong lines of [O I] and Fe II. The Balmer lines show P Cygni profiles; the FWHM of the H alpha emission component is 1250 km/s, and the absorption trough extends to -2000 km/s.

  8. Minutes: Accredited Standards Committee on Acoustics, S1 U.S. Tag for ISO/TC43 Acoustics and IEC/TC29 Electroacoustics

    DTIC Science & Technology

    1991-05-02

    international arena with respect to noise control technology and noise environmental quality In order to give you soma background into the work of the...14 a) A new working groug _S1/WG2Q Ground Impedance................ 14 b) Air Movement and Control Association. Inc. (AMCA...the Air Movement and Control Association (AMCA) on their inquiries concerning ANSI S1.11-1986 Specification for octave-band and fractional-octave-band

  9. A Multi Agent System for Flow-Based Intrusion Detection

    DTIC Science & Technology

    2013-03-01

    Student t-test, as it is less likely to spuriously indicate significance because of the presence of outliers [128]. We use the MATLAB ranksum function [77...effectiveness of self-organization and “ entangled hierarchies” for accomplishing scenario objectives. One of the interesting features of SOMAS is the ability...cross-validation and automatic model selection. It has interfaces for Java, Python, R, Splus, MATLAB , Perl, Ruby, and LabVIEW. Kernels: linear

  10. Minority Undergraduate Research in Prostate Cancer: Bridging Opportunities for Postbaccalaureate Education

    DTIC Science & Technology

    2012-03-01

    students  were  assigned  to  read  both  popular  and   scientific  literature  regarding  the   genetic ,  socio...Biochemistry, Soma Jobbagy, BS Biochemistry, and Erica Boetefuer, Biological Sciences Judging Rubrics for the ASBMB Undergraduate Poster Competition 2007...Bruce Boman, Biological Sciences Role of miRNAs in Regulating Colon Cancer Stem Cells 37) Carrie Barnum and Jennifer Sabatino, Genetics Zohra Ali-Khan

  11. Stability Operations in Somalia 1992-1993: A Case Study

    DTIC Science & Technology

    2016-07-01

    164 Appendix N : Addis Ababa Agreement of the First Session of the Conference on National Reconciliation in Somalia (March 27, 1993...adopted the Addis Abba Agreement of the First Session of the Conference on National Reconciliation in Soma- lia (Appendix N ). In the agreement, all...reaches the starving inland town of Baidoa. December 21, 1992 A mine near Bardera kills Lawrence N . Freedman, a U.S. government civilian employee and

  12. The excitatory/inhibitory input to orexin/hypocretin neuron soma undergoes day/night reorganization.

    PubMed

    Laperchia, Claudia; Imperatore, Roberta; Azeez, Idris A; Del Gallo, Federico; Bertini, Giuseppe; Grassi-Zucconi, Gigliola; Cristino, Luigia; Bentivoglio, Marina

    2017-11-01

    Orexin (OX)/hypocretin-containing neurons are main regulators of wakefulness stability, arousal, and energy homeostasis. Their activity varies in relation to the animal's behavioral state. We here tested whether such variation is subserved by synaptic plasticity phenomena in basal conditions. Mice were sacrificed during day or night, at times when sleep or wake, respectively, predominates, as assessed by electroencephalography in matched mice. Triple immunofluorescence was used to visualize OX-A perikarya and varicosities containing the vesicular glutamate transporter (VGluT)2 or the vesicular GABA transporter (VGAT) combined with synaptophysin (Syn) as a presynaptic marker. Appositions on OX-A + somata were quantitatively analyzed in pairs of sections in epifluorescence and confocal microscopy. The combined total number of glutamatergic (Syn + /VGluT2 + ) and GABAergic (Syn + /VGAT + ) varicosities apposed to OX-A somata was similar during day and night. However, glutamatergic varicosities were significantly more numerous at night, whereas GABAergic varicosities prevailed in the day. Triple immunofluorescence in confocal microscopy was employed to visualize synapse scaffold proteins as postsynaptic markers and confirmed the nighttime prevalence of VGluT2 + together with postsynaptic density protein 95 + excitatory contacts, and daytime prevalence of VGAT + together with gephyrin + inhibitory contacts, while also showing that they formed synapses on OX-A + cell bodies. The findings reveal a daily reorganization of axosomatic synapses in orexinergic neurons, with a switch from a prevalence of excitatory innervation at a time corresponding to wakefulness to a prevalence of inhibitory innervations in the antiphase, at a time corresponding to sleep. This reorganization could represent a key mechanism of plasticity of the orexinergic network in basal conditions.

  13. Co-combustion of pellets from Soma lignite and waste dusts of furniture works

    DOE Office of Scientific and Technical Information (OSTI.GOV)

    Deveci, N.D.; Yilgin, M.; Pehlivan, D.

    2008-07-01

    In this work, volatiles and char combustion behaviors of the fuel pellets prepared from a low quality lignite and the dusts of furniture works and their various blends were investigated in an experimental fixed bed combustion system through which air flowed by natural convection. Combustion data obtained for varied bed temperatures, mass of pellets, and blend compositions has showed that ignition times of the pellets decreased and volatiles combustion rates tended to increase with the burning temperature. It was concluded that some synergy had existed between lignite and lower ratios of furniture work dusts, which was indicated by a promptmore » effect on the volatiles combustion rates. Char combustion rates of blend pellets have depended predominantly on the amount of lignite in the blend. The amounts of combustion residues of the pellets were considerably higher than those calculated from individual ash contents of the raw materials and related to lignite ratio in the blends.« less

  14. Memory, reconsolidation and extinction in Lymnaea require the soma of RPeD1.

    PubMed

    Sangha, Susan; Varshney, Nishi; Fras, Mary; Smyth, Kim; Rosenegger, David; Parvez, Kashif; Sadamoto, Hisayo; Lukowiak, Ken

    2004-01-01

    The central pattern generator (CPG) that drives aerial respiratory behaviour in Lymnaea consists of 3 neurons. One of these, RPeD1--the cell that initiates activity in the circuit, plays an absolutely necessary role as a site for memory formation, memory reconsolidation, and extinction. Using an operant conditioning training procedure that results in a long-term non-declarative memory (LTM), we decrease the occurrence of aerial respiratory behaviour. Since snails can still breathe cutaneously learning this procedure is not harmful. Concomitant with behavioural memory are changes in the spiking activity of RPeD1. Going beyond neural correlates of memory we directly show that RPeD1 is a necessary site for LTM formation. Expanding on this finding we show that this neuron is also a necessary site for memory reconsolidation and 'Pavlovian' extinction. As far as we can determine, this is the first time a single neuron has been shown to be a necessary site for these different aspects memory. RPeD1 is thus a key neuron mediating different hierarchical aspects of memory. We are now in a position to determine the necessary neuronal, molecular and proteomic events in this neuron that are causal to memory formation, reconsolidation and extinction.

  15. Sexually Antagonistic Male Signals Manipulate Germline and Soma of C. elegans Hermaphrodites.

    PubMed

    Aprison, Erin Z; Ruvinsky, Ilya

    2016-10-24

    Males and females pursue different reproductive strategies, which often bring them into conflict-many traits exist that benefit one sex at a cost to another [1]. Decreased female survival following mating dramatically demonstrates one aspect of this phenomenon [2-5]. Particularly intriguing is the evidence that secreted compounds can shorten lifespan of members of the opposite sex in Drosophila [6] and Caenorhabditid nematodes [7] even without copulation taking place. The purpose of such signals is not clear, however. While it is possible that they could limit subsequent mating with competitors or hasten post-reproductive demise, thus decreasing competition for resources, they are also likely to harm unmated individuals. Why would a system exist that reduces the vigor of potential mates prior to mating? Addressing this question could provide insights into mechanisms and evolution of sexual conflict and reveal sensory inputs that regulate aging. Here, we describe two distinct ways in which Caenorhabditis elegans males cause faster somatic aging of hermaphrodites but also manipulate different aspects of their reproductive physiology. The first, mediated by conserved ascaroside pheromones, delays the loss of germline progenitor cells. The second accelerates development, resulting in faster sexual maturation. These signals promote male reproductive strategy and the effects harmful to hermaphrodites appear to be collateral damage rather than the goal. Copyright © 2016 Elsevier Ltd. All rights reserved.

  16. Fabrication of a microfluidic device for the compartmentalization of neuron soma and axons.

    PubMed

    Harris, Joseph; Lee, Hyuna; Vahidi, Behrad; Tu, Christina; Cribbs, David; Jeon, Noo Li; Cotman, Carl

    2007-01-01

    In this video, we demonstrate the technique of soft lithography with polydimethyl siloxane (PDMS) which we use to fabricate a microfluidic device for culturing neurons. Previously, a silicon wafer was patterned with the design for the neuron microfluidic device using SU-8 and photolithography to create a master mold, or what we simply refer to as a "master". Next, we pour the silicon polymer PDMS on top of the master which is then cured by heating the PDMS to 80 degrees C for 1 hour. The PDMS forms a negative mold of the device. The PDMS is then carefully cut and lifted away from the master. Holes are punched where the reservoirs will be and the excess PDMS trimmed away from the device. Nitrogen is used to blow away any excess debris from the device. At this point the devices are now ready for use and can either bonded to corning No. 1 cover glass with a plasma sterilizer/cleaner or can be reversibly bound to the cover glass by simply placing the device on top of the cover glass. The reversible bonding of the device to glass is covered in a separate video and requires first that the device be sterilized either with 70% ethanol or by autoclaving. Plasma treating sterilizes the devices so no further treatment is necessary. It is, however, important, when plasma-treating the devices, to add liquid to the devices within 10 minutes of the plasma treatment while the surfaces are still hydrophilic. Waiting longer than 10 minutes to add liquid to the device makes it difficult for the liquid to enter the device. The neuron devices are typically plasma-bound to cover glass and 0.5 mg/ml poly-L-lysine (PLL) in pH 8.5 borate buffer is immediately added to the device. After a minimum of 3 hours incubating with PLL, the devices are washed with dH2O water a minimum of 3 times with at least 15 minutes between each wash. Next, the water is removed and fresh media is added to the device. At this point the device is ready for use. It is important to remember at this point to never remove all the media from the device. Always leave media in the main channel.

  17. THE DEVELOPMENT OF SEXUAL DIMORPHISM: STUDIES OF THE C. ELEGANS MALE

    PubMed Central

    Emmons, Scott W.

    2014-01-01

    Studies of the development of the C. elegans male have been carried out with the aim of understanding the basis of sexual dimorphism. Postembryonic development of the two C. elegans sexes differs extensively. Development along either the hermaphrodite or male pathway is specified initially by the X to autosome ratio. The regulatory events initiated by this ratio include a male-determining paracrine intercellular signal. Expression of this signal leads to different consequences in three regions of the body: the non-gonadal soma, the somatic parts of the gonad, and the germ line. In the non-gonadal soma, activity of the key Zn-finger transcription factor TRA 1 determines hermaphrodite development; in its absence, the male pathway is followed. Only a few genes directly regulated by TRA 1 are currently known, including members of the evolutionarily conserved, male-determining DM domain Zn-finger transcription factors. In the somatic parts of the gonad and germ line, absence of TRA 1 activity is not sufficient for full expression of the male pathway. Several additional transcription factors involved have been identified. In the germ line, regulatory genes for sperm development that act at the level of RNA in the cytoplasm play a prominent role. PMID:25262817

  18. Characterisation of mouse epididymosomes reveals a complex profile of microRNAs and a potential mechanism for modification of the sperm epigenome

    PubMed Central

    Reilly, Jackson N.; McLaughlin, Eileen A.; Stanger, Simone J.; Anderson, Amanda L.; Hutcheon, Kate; Church, Kiralee; Mihalas, Bettina P.; Tyagi, Sonika; Holt, Janet E.; Eamens, Andrew L.; Nixon, Brett

    2016-01-01

    Recent evidence has shown that the sperm epigenome is vulnerable to dynamic modifications arising from a variety of paternal environment exposures and that this legacy can serve as an important determinant of intergenerational inheritance. It has been postulated that such exchange is communicated to maturing spermatozoa via the transfer of small non-protein-coding RNAs (sRNAs) in a mechanism mediated by epididymosomes; small membrane bound vesicles released by the soma of the male reproductive tract (epididymis). Here we confirm that mouse epididymosomes encapsulate an impressive cargo of >350 microRNAs (miRNAs), a developmentally important sRNA class, the majority (~60%) of which are also represented by the miRNA signature of spermatozoa. This includes >50 miRNAs that were found exclusively in epididymal sperm and epididymosomes, but not in the surrounding soma. We also documented substantial changes in the epididymosome miRNA cargo, including significant fold changes in almost half of the miRNAs along the length of the epididymis. Finally, we provide the first direct evidence for the transfer of several prominent miRNA species between mouse epididymosomes and spermatozoa to afford novel insight into a mechanism of intercellular communication by which the sRNA payload of sperm can be selectively modified during their post-testicular maturation. PMID:27549865

  19. Analyses of non-fatal accidents in an opencast mine by logistic regression model - a case study.

    PubMed

    Onder, Seyhan; Mutlu, Mert

    2017-09-01

    Accidents cause major damage for both workers and enterprises in the mining industry. To reduce the number of occupational accidents, these incidents should be properly registered and carefully analysed. This study efficiently examines the Aegean Lignite Enterprise (ELI) of Turkish Coal Enterprises (TKI) in Soma between 2006 and 2011, and opencast coal mine occupational accident records were used for statistical analyses. A total of 231 occupational accidents were analysed for this study. The accident records were categorized into seven groups: area, reason, occupation, part of body, age, shift hour and lost days. The SPSS package program was used in this study for logistic regression analyses, which predicted the probability of accidents resulting in greater or less than 3 lost workdays for non-fatal injuries. Social facilities-area of surface installations, workshops and opencast mining areas are the areas with the highest probability for accidents with greater than 3 lost workdays for non-fatal injuries, while the reasons with the highest probability for these types of accidents are transporting and manual handling. Additionally, the model was tested for such reported accidents that occurred in 2012 for the ELI in Soma and estimated the probability of exposure to accidents with lost workdays correctly by 70%.

  20. Opposite rheological properties of neuronal microcompartments predict axonal vulnerability in brain injury.

    PubMed

    Grevesse, Thomas; Dabiri, Borna E; Parker, Kevin Kit; Gabriele, Sylvain

    2015-03-30

    Although pathological changes in axonal morphology have emerged as important features of traumatic brain injury (TBI), the mechanical vulnerability of the axonal microcompartment relative to the cell body is not well understood. We hypothesized that soma and neurite microcompartments exhibit distinct mechanical behaviors, rendering axons more sensitive to a mechanical injury. In order to test this assumption, we combined protein micropatterns with magnetic tweezer rheology to probe the viscoelastic properties of neuronal microcompartments. Creep experiments revealed two opposite rheological behaviors within cortical neurons: the cell body was soft and characterized by a solid-like response, whereas the neurite compartment was stiffer and viscous-like. By using pharmacological agents, we demonstrated that the nucleus is responsible for the solid-like behavior and the stress-stiffening response of the soma, whereas neurofilaments have a predominant contribution in the viscous behavior of the neurite. Furthermore, we found that the neurite is a mechanosensitive compartment that becomes softer and adopts a pronounced viscous state on soft matrices. Together, these findings highlight the importance of the regionalization of mechanical and rigidity-sensing properties within neuron microcompartments in the preferential damage of axons during traumatic brain injury and into potential mechanisms of axonal outgrowth after injury.

  1. Opposite rheological properties of neuronal microcompartments predict axonal vulnerability in brain injury

    NASA Astrophysics Data System (ADS)

    Grevesse, Thomas; Dabiri, Borna E.; Parker, Kevin Kit; Gabriele, Sylvain

    2015-03-01

    Although pathological changes in axonal morphology have emerged as important features of traumatic brain injury (TBI), the mechanical vulnerability of the axonal microcompartment relative to the cell body is not well understood. We hypothesized that soma and neurite microcompartments exhibit distinct mechanical behaviors, rendering axons more sensitive to a mechanical injury. In order to test this assumption, we combined protein micropatterns with magnetic tweezer rheology to probe the viscoelastic properties of neuronal microcompartments. Creep experiments revealed two opposite rheological behaviors within cortical neurons: the cell body was soft and characterized by a solid-like response, whereas the neurite compartment was stiffer and viscous-like. By using pharmacological agents, we demonstrated that the nucleus is responsible for the solid-like behavior and the stress-stiffening response of the soma, whereas neurofilaments have a predominant contribution in the viscous behavior of the neurite. Furthermore, we found that the neurite is a mechanosensitive compartment that becomes softer and adopts a pronounced viscous state on soft matrices. Together, these findings highlight the importance of the regionalization of mechanical and rigidity-sensing properties within neuron microcompartments in the preferential damage of axons during traumatic brain injury and into potential mechanisms of axonal outgrowth after injury.

  2. The Hippo Pathway Regulates Homeostatic Growth of Stem Cell Niche Precursors in the Drosophila Ovary

    PubMed Central

    Sarikaya, Didem P.; Extavour, Cassandra G.

    2015-01-01

    The Hippo pathway regulates organ size, stem cell proliferation and tumorigenesis in adult organs. Whether the Hippo pathway influences establishment of stem cell niche size to accommodate changes in organ size, however, has received little attention. Here, we ask whether Hippo signaling influences the number of stem cell niches that are established during development of the Drosophila larval ovary, and whether it interacts with the same or different effector signaling pathways in different cell types. We demonstrate that canonical Hippo signaling regulates autonomous proliferation of the soma, while a novel hippo-independent activity of Yorkie regulates autonomous proliferation of the germ line. Moreover, we demonstrate that Hippo signaling mediates non-autonomous proliferation signals between germ cells and somatic cells, and contributes to maintaining the correct proportion of these niche precursors. Finally, we show that the Hippo pathway interacts with different growth pathways in distinct somatic cell types, and interacts with EGFR and JAK/STAT pathways to regulate non-autonomous proliferation of germ cells. We thus provide evidence for novel roles of the Hippo pathway in establishing the precise balance of soma and germ line, the appropriate number of stem cell niches, and ultimately regulating adult female reproductive capacity. PMID:25643260

  3. A hobo transgene that encodes the P-element transposase in Drosophila melanogaster: autoregulation and cytotype control of transposase activity.

    PubMed Central

    Simmons, Michael J; Haley, Kevin J; Grimes, Craig D; Raymond, John D; Niemi, Jarad B

    2002-01-01

    Drosophila were genetically transformed with a hobo transgene that contains a terminally truncated but otherwise complete P element fused to the promoter from the Drosophila hsp70 gene. Insertions of this H(hsp/CP) transgene on either of the major autosomes produced the P transposase in both the male and female germlines, but not in the soma. Heat-shock treatments significantly increased transposase activity in the female germline; in the male germline, these treatments had little effect. The transposase activity of two insertions of the H(hsp/CP) transgene was not significantly greater than their separate activities, and one insertion of this transgene reduced the transposase activity of P(ry(+), Delta2-3)99B, a stable P transgene, in the germline as well as in the soma. These observations suggest that, through alternate splicing, the H(hsp/CP) transgene produces a repressor that feeds back negatively to regulate transposase expression or function in both the somatic and germline tissues. The H(hsp/CP) transgenes are able to induce gonadal dysgenesis when the transposase they encode has P-element targets to attack. However, this ability and the ability to induce P-element excisions are repressed by the P cytotype, a chromosomal/cytoplasmic state that regulates P elements in the germline. PMID:12019234

  4. Layer 5 Callosal Parvalbumin-Expressing Neurons: A Distinct Functional Group of GABAergic Neurons

    PubMed Central

    Zurita, Hector; Feyen, Paul L. C.; Apicella, Alfonso Junior

    2018-01-01

    Previous studies have shown that parvalbumin-expressing neurons (CC-Parv neurons) connect the two hemispheres of motor and sensory areas via the corpus callosum, and are a functional part of the cortical circuit. Here we test the hypothesis that layer 5 CC-Parv neurons possess anatomical and molecular mechanisms which dampen excitability and modulate the gating of interhemispheric inhibition. In order to investigate this hypothesis we use viral tracing to determine the anatomical and electrophysiological properties of layer 5 CC-Parv and parvalbumin-expressing (Parv) neurons of the mouse auditory cortex (AC). Here we show that layer 5 CC-Parv neurons had larger dendritic fields characterized by longer dendrites that branched farther from the soma, whereas layer 5 Parv neurons had smaller dendritic fields characterized by shorter dendrites that branched nearer to the soma. The layer 5 CC-Parv neurons are characterized by delayed action potential (AP) responses to threshold currents, lower firing rates, and lower instantaneous frequencies compared to the layer 5 Parv neurons. Kv1.1 containing K+ channels are the main source of the AP repolarization of the layer 5 CC-Parv and have a major role in determining both the spike delayed response, firing rate and instantaneous frequency of these neurons. PMID:29559891

  5. Layer 5 Callosal Parvalbumin-Expressing Neurons: A Distinct Functional Group of GABAergic Neurons.

    PubMed

    Zurita, Hector; Feyen, Paul L C; Apicella, Alfonso Junior

    2018-01-01

    Previous studies have shown that parvalbumin-expressing neurons (CC-Parv neurons) connect the two hemispheres of motor and sensory areas via the corpus callosum, and are a functional part of the cortical circuit. Here we test the hypothesis that layer 5 CC-Parv neurons possess anatomical and molecular mechanisms which dampen excitability and modulate the gating of interhemispheric inhibition. In order to investigate this hypothesis we use viral tracing to determine the anatomical and electrophysiological properties of layer 5 CC-Parv and parvalbumin-expressing (Parv) neurons of the mouse auditory cortex (AC). Here we show that layer 5 CC-Parv neurons had larger dendritic fields characterized by longer dendrites that branched farther from the soma, whereas layer 5 Parv neurons had smaller dendritic fields characterized by shorter dendrites that branched nearer to the soma. The layer 5 CC-Parv neurons are characterized by delayed action potential (AP) responses to threshold currents, lower firing rates, and lower instantaneous frequencies compared to the layer 5 Parv neurons. Kv1.1 containing K + channels are the main source of the AP repolarization of the layer 5 CC-Parv and have a major role in determining both the spike delayed response, firing rate and instantaneous frequency of these neurons.

  6. Covariation of axon initial segment location and dendritic tree normalizes the somatic action potential

    PubMed Central

    Hamada, Mustafa S.; Goethals, Sarah; de Vries, Sharon I.; Brette, Romain

    2016-01-01

    In mammalian neurons, the axon initial segment (AIS) electrically connects the somatodendritic compartment with the axon and converts the incoming synaptic voltage changes into a temporally precise action potential (AP) output code. Although axons often emanate directly from the soma, they may also originate more distally from a dendrite, the implications of which are not well-understood. Here, we show that one-third of the thick-tufted layer 5 pyramidal neurons have an axon originating from a dendrite and are characterized by a reduced dendritic complexity and thinner main apical dendrite. Unexpectedly, the rising phase of somatic APs is electrically indistinguishable between neurons with a somatic or a dendritic axon origin. Cable analysis of the neurons indicated that the axonal axial current is inversely proportional to the AIS distance, denoting the path length between the soma and the start of the AIS, and to produce invariant somatic APs, it must scale with the local somatodendritic capacitance. In agreement, AIS distance inversely correlates with the apical dendrite diameter, and model simulations confirmed that the covariation suffices to normalize the somatic AP waveform. Therefore, in pyramidal neurons, the AIS location is finely tuned with the somatodendritic capacitive load, serving as a homeostatic regulation of the somatic AP in the face of diverse neuronal morphologies. PMID:27930291

  7. The extremely divergent maternally- and paternally-transmitted mitochondrial genomes are co-expressed in somatic tissues of two freshwater mussel species with doubly uniparental inheritance of mtDNA

    USGS Publications Warehouse

    Breton, Sophie; Bouvet, Karim; Auclair, Gabrielle; Ghazal, Stephanie; Sietman, Bernard E.; Johnson, Nathan A.; Bettinazzi, Stefano; Dtewart, Donald T.; Guerra, Davide

    2017-01-01

    Freshwater mussel species with doubly uniparental inheritance (DUI) of mtDNA are unique because they are naturally heteroplasmic for two extremely divergent mtDNAs with ~50% amino acid differences for protein-coding genes. The paternally-transmitted mtDNA (or M mtDNA) clearly functions in sperm in these species, but it is still unknown whether it is transcribed when present in male or female soma. In the present study, we used PCR and RT-PCR to detect the presence and expression of the M mtDNA in male and female somatic and gonadal tissues of the freshwater mussel species Venustaconcha ellipsiformis and Utterbackia peninsularis (Unionidae). This is the first study demonstrating that the M mtDNA is transcribed not only in male gonads, but also in male and female soma in freshwater mussels with DUI. Because of the potentially deleterious nature of heteroplasmy, we suggest the existence of different mechanisms in DUI species to deal with this possibly harmful situation, such as silencing mechanisms for the M mtDNA at the transcriptional, post-transcriptional and/or post-translational levels. These hypotheses will necessitate additional studies in distantly-related DUI species that could possess different mechanisms of action to deal with heteroplasmy.

  8. Information transmission in hippocampal CA1 neuron models in the presence of poisson shot noise: the case of periodic sub-threshold spike trains.

    PubMed

    Kawaguchi, Minato; Mino, Hiroyuki; Durand, Dominique M

    2006-01-01

    This article presents an analysis of the information transmission of periodic sub-threshold spike trains in a hippocampal CA1 neuron model in the presence of a homogeneous Poisson shot noise. In the computer simulation, periodic sub-threshold spike trains were presented repeatedly to the midpoint of the main apical branch, while the homogeneous Poisson shot noise was applied to the mid-point of a basal dendrite in the CA1 neuron model consisting of the soma with one sodium, one calcium, and five potassium channels. From spike firing times recorded at the soma, the inter spike intervals were generated and then the probability, p(T), of the inter-spike interval histogram corresponding to the spike interval, r, of the periodic input spike trains was estimated to obtain an index of information transmission. In the present article, it is shown that at a specific amplitude of the homogeneous Poisson shot noise, p(T) was found to be maximized, as well as the possibility to encode the periodic sub-threshold spike trains became greater. It was implied that setting the amplitude of the homogeneous Poisson shot noise to the specific values which maximize the information transmission might contribute to efficiently encoding the periodic sub-threshold spike trains by utilizing the stochastic resonance.

  9. Expression of Vesicular Glutamate Transporters VGLUT1 and VGLUT2 in the Rat Dental Pulp and Trigeminal Ganglion following Inflammation

    PubMed Central

    Hong, Jae Hyun; Kim, Yun Sook; Choi, So Young; Kim, Tae Heon; Cho, Yi Sul; Bae, Yong Chul

    2014-01-01

    Background There is increasing evidence that peripheral glutamate signaling mechanism is involved in the nociceptive transmission during pathological conditions. However, little is known about the glutamate signaling mechanism and related specific type of vesicular glutamate transporter (VGLUT) in the dental pulp following inflammation. To address this issue, we investigated expression and protein levels of VGLUT1 and VGLUT2 in the dental pulp and trigeminal ganglion (TG) following complete Freund’s adjuvant (CFA) application to the rat dental pulp by light microscopic immunohistochemistry and Western blot analysis. Results The density of VGLUT2− immunopositive (+) axons in the dental pulp and the number of VGLUT2+ soma in the TG increased significantly in the CFA-treated group, compared to control group. The protein levels of VGLUT2 in the dental pulp and TG were also significantly higher in the CFA-treated group than control group by Western blot analysis. The density of VGLUT1+ axons in the dental pulp and soma in the TG remained unchanged in the CFA-treated group. Conclusions These findings suggest that glutamate signaling that is mediated by VGLUT2 in the pulpal axons may be enhanced in the inflamed dental pulp, which may contribute to pulpal axon sensitization leading to hyperalgesia following inflammation. PMID:25290694

  10. Expression of vesicular glutamate transporters VGLUT1 and VGLUT2 in the rat dental pulp and trigeminal ganglion following inflammation.

    PubMed

    Yang, Eun Sun; Jin, Myoung Uk; Hong, Jae Hyun; Kim, Yun Sook; Choi, So Young; Kim, Tae Heon; Cho, Yi Sul; Bae, Yong Chul

    2014-01-01

    There is increasing evidence that peripheral glutamate signaling mechanism is involved in the nociceptive transmission during pathological conditions. However, little is known about the glutamate signaling mechanism and related specific type of vesicular glutamate transporter (VGLUT) in the dental pulp following inflammation. To address this issue, we investigated expression and protein levels of VGLUT1 and VGLUT2 in the dental pulp and trigeminal ganglion (TG) following complete Freund's adjuvant (CFA) application to the rat dental pulp by light microscopic immunohistochemistry and Western blot analysis. The density of VGLUT2- immunopositive (+) axons in the dental pulp and the number of VGLUT2+ soma in the TG increased significantly in the CFA-treated group, compared to control group. The protein levels of VGLUT2 in the dental pulp and TG were also significantly higher in the CFA-treated group than control group by Western blot analysis. The density of VGLUT1+ axons in the dental pulp and soma in the TG remained unchanged in the CFA-treated group. These findings suggest that glutamate signaling that is mediated by VGLUT2 in the pulpal axons may be enhanced in the inflamed dental pulp, which may contribute to pulpal axon sensitization leading to hyperalgesia following inflammation.

  11. Effects of hypotonic stress and ouabain on the apparent diffusion coefficient of water at cellular and tissue levels in Aplysia.

    PubMed

    Jelescu, Ileana Ozana; Ciobanu, Luisa; Geffroy, Françoise; Marquet, Pierre; Le Bihan, Denis

    2014-03-01

    There is evidence that physiological or pathological cell swelling is associated with a decrease of the apparent diffusion coefficient (ADC) of water in tissues, as measured with MRI. However the mechanism remains unclear. Magnetic resonance microscopy, performed on small tissue samples, has the potential to distinguish effects occurring at cellular and tissue levels. A three-dimensional diffusion prepared fast imaging with steady-state free precession sequence for MR microscopy was implemented on a 17.2 T imaging system and used to investigate the effect of two biological challenges known to cause cell swelling, exposure to a hypotonic solution or to ouabain, on Aplysia nervous tissue. The ADC was measured inside isolated neuronal soma and in the region of cell bodies of the buccal ganglia. Both challenges resulted in an ADC increase inside isolated neuronal soma (+31 ± 24% and +30 ± 11%, respectively) and an ADC decrease at tissue level in the buccal ganglia (-12 ± 5% and -18 ± 8%, respectively). A scenario involving a layer of water molecules bound to the inflating cell membrane surface is proposed to reconcile this apparent discrepancy. Copyright © 2014 John Wiley & Sons, Ltd.

  12. Synthesis of Feedback Controller for Chaotic Systems by Means of Evolutionary Techniques

    NASA Astrophysics Data System (ADS)

    Senkerik, Roman; Oplatkova, Zuzana; Zelinka, Ivan; Davendra, Donald; Jasek, Roman

    2011-06-01

    This research deals with a synthesis of control law for three selected discrete chaotic systems by means of analytic programming. The novality of the approach is that a tool for symbolic regression—analytic programming—is used for such kind of difficult problem. The paper consists of the descriptions of analytic programming as well as chaotic systems and used cost function. For experimentation, Self-Organizing Migrating Algorithm (SOMA) with analytic programming was used.

  13. Control of Entry to a Queueing System

    DTIC Science & Technology

    1979-11-01

    being devoted to the use of queueing theory to control ard optimize the o~peration i f a system. Here, queueing analyses are used to design a system...operpting costs below somae upper bound while maximizing throughput of the queue. This more recent approach of designing or controlling a queueing system...ports designated as high density traffic airports, the Federal Aviation Administration (FAA) limits the number of instrument flight r’ule (IFR

  14. Laser control of electronic transitions of wave packet by using quadratically chirped pulses.

    PubMed

    Zou, Shiyang; Kondorskiy, Alexey; Mil'nikov, Gennady; Nakamura, Hiroki

    2005-02-22

    An effective scheme is proposed for the laser control of wave packet dynamics. It is demonstrated that by using specially designed quadratically chirped pulses, fast and nearly complete excitation of wave packet can be achieved without significant distortion of its shape. The parameters of the laser pulse can be estimated analytically from the Zhu-Nakamura theory of nonadiabatic transition. If the wave packet is not too narrow or not too broad, then the scheme is expected to be utilizable for multidimensional systems. The scheme is applicable to various processes such as simple electronic excitation, pump-dump, and selective bond breaking, and it is actually numerically demonstrated to work well by taking diatomic and triatomic molecules (LiH, NaK, H(2)O) as examples.

  15. Laser control of electronic transitions of wave packet by using quadratically chirped pulses

    NASA Astrophysics Data System (ADS)

    Zou, Shiyang; Kondorskiy, Alexey; Mil'nikov, Gennady; Nakamura, Hiroki

    2005-02-01

    An effective scheme is proposed for the laser control of wave packet dynamics. It is demonstrated that by using specially designed quadratically chirped pulses, fast and nearly complete excitation of wave packet can be achieved without significant distortion of its shape. The parameters of the laser pulse can be estimated analytically from the Zhu-Nakamura theory of nonadiabatic transition. If the wave packet is not too narrow or not too broad, then the scheme is expected to be utilizable for multidimensional systems. The scheme is applicable to various processes such as simple electronic excitation, pump-dump, and selective bond breaking, and it is actually numerically demonstrated to work well by taking diatomic and triatomic molecules (LiH, NaK, H2O) as examples.

  16. Some Remarks on the Acoustics of the Piano

    NASA Astrophysics Data System (ADS)

    Giordano, Nicholas

    Much has been written about the piano. There are a number of excellent books and research articles that discuss the history, evolution, and acoustics of the instrument (Fletcher and Rossing 1991; Pollens 1995; Suzuki and Nakamura 1990; Conklin 1996a, b, c; Good 2001). However, most of these sources are either at a very qualitative level or aimed at the dedicated acoustician. Our goal in this chapter is to bridge these two extremes and to show how some elementary knowledge of physics and acoustics in general, and of the piano in particular, give interesting insight to the nature and composition of a piano tone. We hope that the next few pages will be of interest to scientists and nonscientists alike.

  17. Muscle length-dependent contribution of motoneuron Cav1.3 channels to force production in model slow motor unit.

    PubMed

    Kim, Hojeong

    2017-07-01

    Persistent inward current (PIC)-generating Ca v 1.3 channels in spinal motoneuron dendrites are thought to be actively recruited during normal behaviors. However, whether and how the activation of PIC channels influences force output of motor unit remains elusive. Here, building a physiologically realistic model of slow motor unit I demonstrated that force production induced by the PIC activation is much smaller for short than lengthened muscles during the regular firing of the motoneuron that transitions from the quiescent state by either a brief current pulse at the soma or a brief synaptic excitation at the dendrites. By contrast, the PIC-induced force potentiation was maximal for short muscles when the motoneuron switched from a stable low-frequency firing state to a stable high-frequency firing state by the current pulse at the soma. Under the synaptic excitation at the dendrites, however, the force could not be potentiated by the transitioning of the motoneuron from a low- to a high-frequency firing state due to the simultaneous onset of PIC at the dendrites and firing at the soma. The strong dependency of the input-output relationship of the motor unit on the neuromodulation and Ia afferent inputs for the PIC channels was further shown under static variations in muscle length. Taken together, these findings suggest that the PIC activation in the motoneuron dendrites may differentially affect the force production of the motor unit, depending not only on the firing state history of the motoneuron and the variation in muscle length but also on the mode of motor activity. NEW & NOTEWORTHY Ca v 1.3 channels in motoneuron dendrites are actively involved during normal motor activities. To investigate the effects of the activation of motoneuron Ca v 1.3 channels on force production, a model motor unit was built based on best-available data. The simulation results suggest that force potentiation induced by Ca v 1.3 channel activation is strongly modulated not only by

  18. Development of Ca2+ hotspots between Lymnaea neurons during synaptogenesis

    PubMed Central

    Feng, Zhong-Ping; Grigoriev, Nikita; Munno, David; Lukowiak, Ken; MacVicar, Brian A; Goldberg, Jeffrey I; Syed, Naweed I

    2002-01-01

    Calcium (Ca2+) channel clustering at specific presynaptic sites is a hallmark of mature synapses. However, the spatial distribution patterns of Ca2+ channels at newly formed synapses have not yet been demonstrated. Similarly, it is unclear whether Ca2+ ‘hotspots’ often observed at the presynaptic sites are indeed target cell contact specific and represent a specialized mechanism by which Ca2+ channels are targeted to select synaptic sites. Utilizing both soma–soma paired (synapsed) and single neurons from the mollusk Lymnaea, we have tested the hypothesis that differential gradients of voltage-dependent Ca2+ signals develop in presynaptic neuron at its contact point with the postsynaptic neuron; and that these Ca2+ hotspots are target cell contact specific. Fura-2 imaging, or two-photon laser scanning microscopy of Calcium Green, was coupled with electrophysiological techniques to demonstrate that voltage-induced Ca2+ gradients (hotspots) develop in the presynaptic cell at its contact point with the postsynaptic neuron, but not in unpaired single cells. The incidence of Ca2+ hotspots coincided with the appearance of synaptic transmission between the paired cells, and these gradients were target cell contact specific. In contrast, the voltage-induced Ca2+ signal in unpaired neurons was uniformly distributed throughout the somata; a similar pattern of Ca2+ gradient was observed in the presynaptic neuron when it was soma–soma paired with a non-synaptic partner cell. Moreover, voltage clamp recording techniques, in conjunction with a fast, optical differential perfusion system, were used to demonstrate that the total whole-cell Ca2+ (or Ba2+) current density in single and paired cells was not significantly different. However, the amplitude of Ba2+ current was significantly higher in the presynaptic cell at its contact side with the postsynaptic neurons, compared with non-contacted regions. In summary, this study demonstrates that voltage-induced Ca2+ hotspots

  19. Random-access scanning microscopy for 3D imaging in awake behaving animals

    PubMed Central

    Nadella, K. M. Naga Srinivas; Roš, Hana; Baragli, Chiara; Griffiths, Victoria A.; Konstantinou, George; Koimtzis, Theo; Evans, Geoffrey J.; Kirkby, Paul A.; Silver, R. Angus

    2018-01-01

    Understanding how neural circuits process information requires rapid measurements from identified neurons distributed in 3D space. Here we describe an acousto-optic lens two-photon microscope that performs high-speed focussing and line-scanning within a volume spanning hundreds of micrometres. We demonstrate its random access functionality by selectively imaging cerebellar interneurons sparsely distributed in 3D and by simultaneously recording from the soma, proximal and distal dendrites of neocortical pyramidal cells in behaving mice. PMID:27749836

  20. Lung Reference Set C Application: Rachel Ostroff - SomaLogics (2010) — EDRN Public Portal

    Cancer.gov

    Analysis of the EDRN lung biomarker samples will enable the next step in development of a clinical diagnostic assay for the differential diagnosis of lung cancer or benign disease in patients with indeterminant pulmonary nodules. The objective is to develop a blood test with sufficient accuracy to identify lung cancer in these patients, which will aid the treating physician in decisions to recommend invasive procedures or watchful waiting.

  1. [Fifty years of psychiatry at the interface between psyche and soma: a SWOT analysis].

    PubMed

    van Houdenhove, B; Luyten, P

    2008-01-01

    During the past 50 years the border area between psychiatry and somatic medicine has undergone remarkable changes. Theories have become better-founded, both psychologically and neurobiologically, research has become more sophisticated, and liaison-psychiatrists and health psychiatrist/behavioural medicine psychologists have played an increasingly active role in this domain. At the beginning of the 21st century modern psychosomatic medicine is facing new challenges; these include how to create a workable diagnostic classification system, how to instruct and educate both health professionals and lay-persons to an adequate level, how to utilize innovative research paradigms without having recourse to reductionism and how to implement in medical practice treatments that are geared to the needs of the individual patient.

  2. Regulation of the X Chromosome in the Germline and Soma of Drosophila melanogaster Males.

    PubMed

    Argyridou, Eliza; Parsch, John

    2018-05-04

    During the evolution of heteromorphic sex chromosomes, the sex-specific Y chromosome degenerates, while the X chromosome evolves new mechanisms of regulation. Using bioinformatic and experimental approaches, we investigate the expression of the X chromosome in Drosophila melanogaster . We observe nearly complete X chromosome dosage compensation in male somatic tissues, but not in testis. The X chromosome contains disproportionately fewer genes with high expression in testis than the autosomes, even after accounting for the lack of dosage compensation, which suggests that another mechanism suppresses their expression in the male germline. This is consistent with studies of reporter genes and transposed genes, which find that the same gene has higher expression when autosomal than when X-linked. Using a new reporter gene that is expressed in both testis and somatic tissues, we find that the suppression of X-linked gene expression is limited to genes with high expression in testis and that the extent of the suppression is positively correlated with expression level.

  3. NMDA Receptor Subunits Change after Synaptic Plasticity Induction and Learning and Memory Acquisition.

    PubMed

    Baez, María Verónica; Cercato, Magalí Cecilia; Jerusalinsky, Diana Alicia

    2018-01-01

    NMDA ionotropic glutamate receptors (NMDARs) are crucial in activity-dependent synaptic changes and in learning and memory. NMDARs are composed of two GluN1 essential subunits and two regulatory subunits which define their pharmacological and physiological profile. In CNS structures involved in cognitive functions as the hippocampus and prefrontal cortex, GluN2A and GluN2B are major regulatory subunits; their expression is dynamic and tightly regulated, but little is known about specific changes after plasticity induction or memory acquisition. Data strongly suggest that following appropriate stimulation, there is a rapid increase in surface GluN2A-NMDAR at the postsynapses, attributed to lateral receptor mobilization from adjacent locations. Whenever synaptic plasticity is induced or memory is consolidated, more GluN2A-NMDARs are assembled likely using GluN2A from a local translation and GluN1 from local ER. Later on, NMDARs are mobilized from other pools, and there are de novo syntheses at the neuron soma. Changes in GluN1 or NMDAR levels induced by synaptic plasticity and by spatial memory formation seem to occur in different waves of NMDAR transport/expression/degradation, with a net increase at the postsynaptic side and a rise in expression at both the spine and neuronal soma. This review aims to put together that information and the proposed hypotheses.

  4. Localization of P-type calcium channels in the central nervous system.

    PubMed Central

    Hillman, D; Chen, S; Aung, T T; Cherksey, B; Sugimori, M; Llinás, R R

    1991-01-01

    The distribution of the P-type calcium channel in the mammalian central nervous system has been demonstrated immunohistochemically by using a polyclonal specific antibody. This antibody was generated after P-channel isolation via a fraction from funnel-web spider toxin (FTX) that blocks the voltage-gated P channels in cerebellar Purkinje cells. In the cerebellar cortex, immunolabeling to the antibody appeared throughout the molecular layer, while all the other regions were negative. Intensely labeled patches of reactivity were seen on Purkinje cell dendrites, especially at bifurcations; much weaker reactivity was present in the soma and stem segment. Electron microscopic localization revealed labeled patches of plasma membrane on the soma, main dendrites, spiny branchlets, and spines; portions of the smooth endoplasmic reticulum were also labeled. Strong labeling was present in the periglomerular cells of the olfactory bulb and scattered neurons in the deep layer of the entorhinal and pyriform cortices. Neurons in the brainstem, habenula, nucleus of the trapezoid body and inferior olive and along the floor of the fourth ventricle were also labeled intensely. Medium-intensity reactions were observed in layer II pyramidal cells of the frontal cortex, the CA1 cells of the hippocampus, the lateral nucleus of the substantia nigra, lateral reticular nucleus, and spinal fifth nucleus. Light labeling was seen in the neocortex, striatum, and in some brainstem neurons. Images PMID:1651493

  5. Localization of P-type calcium channels in the central nervous system.

    PubMed

    Hillman, D; Chen, S; Aung, T T; Cherksey, B; Sugimori, M; Llinás, R R

    1991-08-15

    The distribution of the P-type calcium channel in the mammalian central nervous system has been demonstrated immunohistochemically by using a polyclonal specific antibody. This antibody was generated after P-channel isolation via a fraction from funnel-web spider toxin (FTX) that blocks the voltage-gated P channels in cerebellar Purkinje cells. In the cerebellar cortex, immunolabeling to the antibody appeared throughout the molecular layer, while all the other regions were negative. Intensely labeled patches of reactivity were seen on Purkinje cell dendrites, especially at bifurcations; much weaker reactivity was present in the soma and stem segment. Electron microscopic localization revealed labeled patches of plasma membrane on the soma, main dendrites, spiny branchlets, and spines; portions of the smooth endoplasmic reticulum were also labeled. Strong labeling was present in the periglomerular cells of the olfactory bulb and scattered neurons in the deep layer of the entorhinal and pyriform cortices. Neurons in the brainstem, habenula, nucleus of the trapezoid body and inferior olive and along the floor of the fourth ventricle were also labeled intensely. Medium-intensity reactions were observed in layer II pyramidal cells of the frontal cortex, the CA1 cells of the hippocampus, the lateral nucleus of the substantia nigra, lateral reticular nucleus, and spinal fifth nucleus. Light labeling was seen in the neocortex, striatum, and in some brainstem neurons.

  6. Location-dependent excitatory synaptic interactions in pyramidal neuron dendrites.

    PubMed

    Behabadi, Bardia F; Polsky, Alon; Jadi, Monika; Schiller, Jackie; Mel, Bartlett W

    2012-01-01

    Neocortical pyramidal neurons (PNs) receive thousands of excitatory synaptic contacts on their basal dendrites. Some act as classical driver inputs while others are thought to modulate PN responses based on sensory or behavioral context, but the biophysical mechanisms that mediate classical-contextual interactions in these dendrites remain poorly understood. We hypothesized that if two excitatory pathways bias their synaptic projections towards proximal vs. distal ends of the basal branches, the very different local spike thresholds and attenuation factors for inputs near and far from the soma might provide the basis for a classical-contextual functional asymmetry. Supporting this possibility, we found both in compartmental models and electrophysiological recordings in brain slices that the responses of basal dendrites to spatially separated inputs are indeed strongly asymmetric. Distal excitation lowers the local spike threshold for more proximal inputs, while having little effect on peak responses at the soma. In contrast, proximal excitation lowers the threshold, but also substantially increases the gain of distally-driven responses. Our findings support the view that PN basal dendrites possess significant analog computing capabilities, and suggest that the diverse forms of nonlinear response modulation seen in the neocortex, including uni-modal, cross-modal, and attentional effects, could depend in part on pathway-specific biases in the spatial distribution of excitatory synaptic contacts onto PN basal dendritic arbors.

  7. Biophysical properties and computational modeling of calcium spikes in serotonergic neurons of the dorsal raphe nucleus.

    PubMed

    Tuckwell, Henry C

    2013-06-01

    Serotonergic neurons of the dorsal raphe nuclei, with their extensive innervation of nearly the whole brain have important modulatory effects on many cognitive and physiological processes. They play important roles in clinical depression and other psychiatric disorders. In order to quantify the effects of serotonergic transmission on target cells it is desirable to construct computational models and to this end these it is necessary to have details of the biophysical and spike properties of the serotonergic neurons. Here several basic properties are reviewed with data from several studies since the 1960s to the present. The quantities included are input resistance, resting membrane potential, membrane time constant, firing rate, spike duration, spike and afterhyperpolarization (AHP) amplitude, spike threshold, cell capacitance, soma and somadendritic areas. The action potentials of these cells are normally triggered by a combination of sodium and calcium currents which may result in autonomous pacemaker activity. We here analyse the mechanisms of high-threshold calcium spikes which have been demonstrated in these cells the presence of TTX (tetrodotoxin). The parameters for calcium dynamics required to give calcium spikes are quite different from those for regular spiking which suggests the involvement of restricted parts of the soma-dendritic surface as has been found, for example, in hippocampal neurons. Copyright © 2013 Elsevier Ireland Ltd. All rights reserved.

  8. Clinical progression in Parkinson disease and the neurobiology of axons.

    PubMed

    Cheng, Hsiao-Chun; Ulane, Christina M; Burke, Robert E

    2010-06-01

    Despite tremendous growth in recent years in our knowledge of the molecular basis of Parkinson disease (PD) and the molecular pathways of cell injury and death, we remain without therapies that forestall disease progression. Although there are many possible explanations for this lack of success, one is that experimental therapeutics to date have not adequately focused on an important component of the disease process, that of axon degeneration. It remains unknown what neuronal compartment, either the soma or the axon, is involved at disease onset, although some have proposed that it is the axons and their terminals that take the initial brunt of injury. Nevertheless, this concept has not been formally incorporated into many of the current theories of disease pathogenesis, and it has not achieved a wide consensus. More importantly, in view of growing evidence that the molecular mechanisms of axon degeneration are separate and distinct from the canonical pathways of programmed cell death that mediate soma destruction, the possibility of early involvement of axons in PD has not been adequately emphasized as a rationale to explore the neurobiology of axons for novel therapeutic targets. We propose that ongoing degeneration of axons, not cell bodies, is the primary determinant of clinically apparent progression of disease, and that future experimental therapeutics intended to forestall disease progression will benefit from a new focus on the distinct mechanisms of axon degeneration.

  9. The association of rectal equivalent dose in 2 Gy fractions (EQD2) to late rectal toxicity in locally advanced cervical cancer patients who were evaluated by rectosigmoidoscopy in Faculty of Medicine, Chiang Mai University.

    PubMed

    Tharavichtikul, Ekkasit; Meungwong, Pooriwat; Chitapanarux, Taned; Chakrabandhu, Somvilai; Klunklin, Pitchayaponne; Onchan, Wimrak; Wanwilairat, Somsak; Traisathit, Patrinee; Galalae, Razvan; Chitapanarux, Imjai

    2014-06-01

    To evaluate association between equivalent dose in 2 Gy (EQD2) to rectal point dose and gastrointestinal toxicity from whole pelvic radiotherapy (WPRT) and intracavitary brachytherapy (ICBT) in cervical cancer patients who were evaluated by rectosigmoidoscopy in Faculty of Medicine, Chiang Mai University. Retrospective study was designed for the patients with locally advanced cervical cancer, treated by radical radiotherapy from 2004 to 2009 and were evaluated by rectosigmoidoscopy. The cumulative doses of WPRT and ICBT to the maximally rectal point were calculated to the EQD2 and evaluated the association of toxicities. Thirty-nine patients were evaluated for late rectal toxicity. The mean cumulative dose in term of EQD2 to rectum was 64.2 Gy. Grade 1 toxicities were the most common findings. According to endoscopic exam, the most common toxicities were congested mucosa (36 patients) and telangiectasia (32 patients). In evaluation between rectal dose in EQD2 and toxicities, no association of cumulative rectal dose to rectal toxicity, except the association of cumulative rectal dose in EQD2 >65 Gy to late effects of normal tissue (LENT-SOMA) scale ≥ grade 2 (p = 0.022; odds ratio, 5.312; 95% confidence interval, 1.269-22.244). The cumulative rectal dose in EQD2 >65 Gy have association with ≥ grade 2 LENT-SOMA scale.

  10. The association of rectal equivalent dose in 2 Gy fractions (EQD2) to late rectal toxicity in locally advanced cervical cancer patients who were evaluated by rectosigmoidoscopy in Faculty of Medicine, Chiang Mai University

    PubMed Central

    Meungwong, Pooriwat; Chitapanarux, Taned; Chakrabandhu, Somvilai; Klunklin, Pitchayaponne; Onchan, Wimrak; Wanwilairat, Somsak; Traisathit, Patrinee; Galalae, Razvan; Chitapanarux, Imjai

    2014-01-01

    Purpose To evaluate association between equivalent dose in 2 Gy (EQD2) to rectal point dose and gastrointestinal toxicity from whole pelvic radiotherapy (WPRT) and intracavitary brachytherapy (ICBT) in cervical cancer patients who were evaluated by rectosigmoidoscopy in Faculty of Medicine, Chiang Mai University. Materials and Methods Retrospective study was designed for the patients with locally advanced cervical cancer, treated by radical radiotherapy from 2004 to 2009 and were evaluated by rectosigmoidoscopy. The cumulative doses of WPRT and ICBT to the maximally rectal point were calculated to the EQD2 and evaluated the association of toxicities. Results Thirty-nine patients were evaluated for late rectal toxicity. The mean cumulative dose in term of EQD2 to rectum was 64.2 Gy. Grade 1 toxicities were the most common findings. According to endoscopic exam, the most common toxicities were congested mucosa (36 patients) and telangiectasia (32 patients). In evaluation between rectal dose in EQD2 and toxicities, no association of cumulative rectal dose to rectal toxicity, except the association of cumulative rectal dose in EQD2 >65 Gy to late effects of normal tissue (LENT-SOMA) scale ≥ grade 2 (p = 0.022; odds ratio, 5.312; 95% confidence interval, 1.269-22.244). Conclusion The cumulative rectal dose in EQD2 >65 Gy have association with ≥ grade 2 LENT-SOMA scale. PMID:25061573

  11. Extrachromosomal circular DNA-based amplification and transmission of herbicide resistance in crop weed Amaranthus palmeri

    PubMed Central

    Koo, Dal-Hoe; Molin, William T.; Saski, Christopher A.; Jiang, Jiming; Putta, Karthik; Friebe, Bernd; Gill, Bikram S.

    2018-01-01

    Gene amplification has been observed in many bacteria and eukaryotes as a response to various selective pressures, such as antibiotics, cytotoxic drugs, pesticides, herbicides, and other stressful environmental conditions. An increase in gene copy number is often found as extrachromosomal elements that usually contain autonomously replicating extrachromosomal circular DNA molecules (eccDNAs). Amaranthus palmeri, a crop weed, can develop herbicide resistance to glyphosate [N-(phosphonomethyl) glycine] by amplification of the 5-enolpyruvylshikimate-3-phosphate synthase (EPSPS) gene, the molecular target of glyphosate. However, biological questions regarding the source of the amplified EPSPS, the nature of the amplified DNA structures, and mechanisms responsible for maintaining this gene amplification in cells and their inheritance remain unknown. Here, we report that amplified EPSPS copies in glyphosate-resistant (GR) A. palmeri are present in the form of eccDNAs with various conformations. The eccDNAs are transmitted during cell division in mitosis and meiosis to the soma and germ cells and the progeny by an as yet unknown mechanism of tethering to mitotic and meiotic chromosomes. We propose that eccDNAs are one of the components of McClintock’s postulated innate systems [McClintock B (1978) Stadler Genetics Symposium] that can rapidly produce soma variation, amplify EPSPS genes in the sporophyte that are transmitted to germ cells, and modulate rapid glyphosate resistance through genome plasticity and adaptive evolution. PMID:29531028

  12. Retrograde and Wallerian Axonal Degeneration Occur Synchronously after Retinal Ganglion Cell Axotomy

    PubMed Central

    Kanamori, Akiyasu; Catrinescu, Maria-Magdalena; Belisle, Jonathan M.; Costantino, Santiago; Levin, Leonard A.

    2013-01-01

    Axonal injury and degeneration are pivotal pathological events in diseases of the nervous system. In the past decade, it has been recognized that the process of axonal degeneration is distinct from somal degeneration and that axoprotective strategies may be distinct from those that protect the soma. Preserving the cell body via neuroprotection cannot improve function if the axon is damaged, because the soma is still disconnected from its target. Therefore, understanding the mechanisms of axonal degeneration is critical for developing new therapeutic interventions for axonal disease treatment. We combined in vivo imaging with a multilaser confocal scanning laser ophthalmoscope and in vivo axotomy with a diode-pumped solid-state laser to assess the time course of Wallerian and retrograde degeneration of unmyelinated retinal ganglion cell axons in living rats for 4 weeks after intraretinal axotomy. Laser injury resulted in reproducible axon loss both distal and proximal to the site of injury. Longitudinal polarization-sensitive imaging of axons demonstrated that Wallerian and retrograde degeneration occurred synchronously. Neurofilament immunostaining of retinal whole-mounts confirmed axonal loss and demonstrated sparing of adjacent axons to the axotomy site. In vivo fluorescent imaging of axonal transport and photobleaching of labeled axons demonstrated that the laser axotomy model did not affect adjacent axon function. These results are consistent with a shared mechanism for Wallerian and retrograde degeneration. PMID:22642911

  13. A Comparative study for striatal-direct and -indirect pathway neurons to DA depletion-induced lesion in a PD rat model.

    PubMed

    Zheng, Xuefeng; Wu, Jiajia; Zhu, Yaofeng; Chen, Si; Chen, Zhi; Chen, Tao; Huang, Ziyun; Wei, Jiayou; Li, Yanmei; Lei, Wanlong

    2018-04-16

    Striatal-direct and -indirect Pathway Neurons showed different vulnerability in basal ganglia disorders. Therefore, present study aimed to examine and compare characteristic changes of densities, protein and mRNA levels of soma, dendrites, and spines between striatal-direct and -indirect pathway neurons after DA depletion by using immunohistochemistry, Western blotting, real-time PCR and immunoelectron microscopy techniques. Experimental results showed that: 1) 6OHDA-induced DA depletion decreased the soma density of striatal-direct pathway neurons (SP+), but no significant changes for striatal-indirect pathway neurons (ENK+). 2) DA depletion resulted in a decline of dendrite density for both striatal-direct (D1+) and -indirect (D2+) pathway neurons, and D2+ dendritic density declined more obviously. At the ultrastructure level, the densities of D1+ and D2+ dendritic spines reduced in the 6OHDA groups compared with their control groups, but the density of D2+ dendritic spines reduced more significant than that of D1. 3) Striatal DA depletion down-regulated protein and mRNA expression levels of SP and D1, on the contrary, ENK and D2 protein and mRNA levels of indirect pathway neurons were up-regulated significantly. Present results suggested that indirect pathway neurons be more sensitive to 6OHDA-induced DA depletion. Copyright © 2018 Elsevier Ltd. All rights reserved.

  14. Pacemaker rate and depolarization block in nigral dopamine neurons: a somatic sodium channel balancing act

    PubMed Central

    Tucker, Kristal R.; Huertas, Marco A.; Horn, John P.; Canavier, Carmen C.; Levitan, Edwin S.

    2012-01-01

    Midbrain dopamine (DA) neurons are slow intrinsic pacemakers that undergo depolarization (DP) block upon moderate stimulation. Understanding DP block is important because it has been correlated with the clinical efficacy of chronic antipsychotic drug treatment. Here we describe how voltage-gated sodium (NaV) channels regulate DP block and pacemaker activity in DA neurons of the substantia nigra using rat brain slices. The distribution, density and gating of NaV currents were manipulated by blocking native channels with tetrodotoxin and by creating virtual channels and anti-channels with dynamic clamp. Although action potentials initiate in the axon initial segment (AIS) and NaV channels are distributed in multiple dendrites, selective reduction of NaV channel activity in the soma was sufficient to decrease pacemaker frequency and increase susceptibility to DP block. Conversely, increasing somatic NaV current density raised pacemaker frequency and lowered susceptibility to DP block. Finally, when NaV currents were restricted to the soma, pacemaker activity occurred at abnormally high rates due to excessive local subthreshold NaV current. Together with computational simulations, these data show that both the slow pacemaker rate and the sensitivity to DP block that characterizes DA neurons result from the low density of somatic NaV channels. More generally, we conclude that the somatodendritic distribution of NaV channels is a major determinant of repetitive spiking frequency. PMID:23077037

  15. Nerve Conduction Through Dendrites via Proton Hopping.

    PubMed

    Kier, Lemont B

    2017-01-01

    In our previous studies of nerve conduction conducted by proton hopping, we have considered the axon, soma, synapse and the nodes of Ranvier. The role of proton hopping described the passage of information through each of these units of a typical nerve system. The synapse projects information from the axon to the dendrite and their associated spines. We have invoked the passage of protons via a hopping mechanism to illustrate the continuum of the impulse through the system, via the soma following the dendrites. This is proposed to be a continuum invoked by the proton hopping method. With the proposal of the activity through the dendrites, via proton hopping, a complete model of the nerve function is invoked. At each step to the way, a water pathway is present and is invoked in the proposed model as the carrier of the message via proton hopping. The importance of the dendrites is evident by the presence of a vast number of spines, each possessing the possibility to carry unique messages through the nervous system. With this model of the role of dendrites, functioning with the presence of proton hopping, a complete model of the nerve system is presented. The validity of this model will be available for further studies and models to assess it's validity. Copyright© Bentham Science Publishers; For any queries, please email at epub@benthamscience.org.

  16. Brain-derived neurotrophic factor/neurotrophin 3 regulate axon initial segment location and affect neuronal excitability in cultured hippocampal neurons.

    PubMed

    Guo, Yu; Su, Zi-Jun; Chen, Yi-Kun; Chai, Zhen

    2017-07-01

    Plasticity of the axon initial segment (AIS) has aroused great interest in recent years because it regulates action potential initiation and neuronal excitability. AIS plasticity manifests as modulation of ion channels or variation in AIS structure. However, the mechanisms underlying structural plasticity of the AIS are not well understood. Here, we combined immunofluorescence, patch-clamp recordings, and pharmacological methods in cultured hippocampal neurons to investigate the factors participating in AIS structural plasticity during development. With lowered neuronal density, the distance between the AIS and the soma increased, while neuronal excitability decreased, as shown by the increased action potential threshold and current threshold for firing an action potential. This variation in the location of the AIS was associated with cellular secretory substances, including brain-derived neurotrophic factor (BDNF) and neurotrophin 3 (NT3). Indeed, blocking BDNF and NT3 with TrkB-Fc eliminated the effect of conditioned medium collected from high-density cultures on AIS relocation. Elevating the extracellular concentration of BDNF or NT3 promoted movement of the AIS proximally to the soma and increased neuronal excitability. Furthermore, knockdown of neurotrophin receptors TrkB and TrkC caused distal movement of the AIS. Our results demonstrate that BDNF and NT3 regulate AIS location and neuronal excitability. These regulatory functions of neurotrophic factors provide insight into the molecular mechanisms underlying AIS biology. © 2017 International Society for Neurochemistry.

  17. Automated customized retrieval of radiotherapy data for clinical trials, audit and research.

    PubMed

    Romanchikova, Marina; Harrison, Karl; Burnet, Neil G; Hoole, Andrew Cf; Sutcliffe, Michael Pf; Parker, Michael Andrew; Jena, Rajesh; Thomas, Simon James

    2018-02-01

    To enable fast and customizable automated collection of radiotherapy (RT) data from tomotherapy storage. Human-readable data maps (TagMaps) were created to generate DICOM-RT (Digital Imaging and Communications in Medicine standard for Radiation Therapy) data from tomotherapy archives, and provided access to "hidden" information comprising delivery sinograms, positional corrections and adaptive-RT doses. 797 data sets totalling 25,000 scans were batch-exported in 31.5 h. All archived information was restored, including the data not available via commercial software. The exported data were DICOM-compliant and compatible with major commercial tools including RayStation, Pinnacle and ProSoma. The export ran without operator interventions. The TagMap method for DICOM-RT data modelling produced software that was many times faster than the vendor's solution, required minimal operator input and delivered high volumes of vendor-identical DICOM data. The approach is applicable to many clinical and research data processing scenarios and can be adapted to recover DICOM-RT data from other proprietary storage types such as Elekta, Pinnacle or ProSoma. Advances in knowledge: A novel method to translate data from proprietary storage to DICOM-RT is presented. It provides access to the data hidden in electronic archives, offers a working solution to the issues of data migration and vendor lock-in and paves the way for large-scale imaging and radiomics studies.

  18. SU-E-T-278: Dose Conformity Index for the Target in a Multitarget Environment

    DOE Office of Scientific and Technical Information (OSTI.GOV)

    Harikrishnaperumal, Sudahar

    2015-06-15

    Purpose: The existing conformity index formulations are failing when multiple targets present outside the target of interest with same or different dose prescriptions. In the present study a novel methodology is introduced to solve this issue. Methods: The conformity index used by Nakamura et al (Int J Radiat Oncol Biol Phys 2001; 51(5):1313–1319) is taken as the base for this methodology. In this proposal, the prescription isodose volume (PIV) which normally includes the normal tissue and other target regions is restricted as PIV in annular regions of different thickness around the target of interest. The graphical line plotted between themore » thickness of annular region and the corresponding conformity index, will increase in the beginning and will reach a flat region, then it will increase again. The second increase in the conformity index depends basically on the distance between the targets, dose prescriptions, and size of the targets. The conformity index in the flat region should be the conformity index of the target of interest. This methodology was validated on dual target environment on a skull phantom in Multiplan planning system (Accuray Inc. Sunnyvale, USA) Results: When the surrounding target’s (sphere) size is changed from 1.5cm to 6cm diameter, the conformity index of the target of interest (3cm diameter) changed from 1.09 to 1.25. When the distance between the targets changed from 7.5cm to 2.5cm, the conformity index changed from 1.10 to 1.17. Similarly, when the prescribed dose changed from 25Gy to 50Gy the conformity index changed from 1.09 to 1.42. These values were above 2.0 when Nakamura et al formula was used. Conclusion: The proposed conformity index methodology eliminates the influence of surrounding targets to a greater extend. However, the limitations of this method should be studied further. Application of this method in clinical situations is the future scope.« less

  19. IO-MFA and Thermodynamic Approach for Metal Recycling

    NASA Astrophysics Data System (ADS)

    Nakajima, Kenichi; Matsubae, Kazuyo; Kondo, Yasushi; Nakamura, Shinichiro; Nagasaka, Tetsuya

    Recently, the issue of sustainable resource management has been increasingly recognized. In order to increase resource efficiency, Castro et al. (2004) pointed out an importance to understand the interconnections between the materials' processing routes and their thermodynamic constraints, and discussed losses due to contaminations during recycling. One of the dominant solutions to avoid such losses or contaminants is knowledge about the substance flows in material cycles. Material flow analysis (MFA) is a powerful tool to understand the resource consumption and material cycle in the national economy. Some advanced MFA studies discussed the complex web of metal flows and their linkages (Nakamura et al. 2007, 2008). Discussions on the limitations of impurity removal and the recoverability of elements in the recycling of EoL metal products, however, have been insufficient even in conventional MFA studies.

  20. Novel Combinatory Approaches to Repair Visual System after Optic Nerve Damage

    DTIC Science & Technology

    2014-09-01

    Intravitreal Viral Treatment Outcome Measures PTEN/SOCS3f/f AAV-GFP (Control) RGC staining and axon tracing PTEN/SOCS3f/f AAV-Cre “ “ CHOP-/- AAV-XBP1...survival and axon regeneration using immunohistochemistry and axon tracing methods used in our previous studies. At 4 and 8 weeks after injury, retinas...the cell body. After peripheral nerve injury, phosphorylated (i.e., active) STAT3 is detected in the injured axons and later in the soma (Lee, Neitzel

  1. Spiking Neurons for Analysis of Patterns

    NASA Technical Reports Server (NTRS)

    Huntsberger, Terrance

    2008-01-01

    Artificial neural networks comprising spiking neurons of a novel type have been conceived as improved pattern-analysis and pattern-recognition computational systems. These neurons are represented by a mathematical model denoted the state-variable model (SVM), which among other things, exploits a computational parallelism inherent in spiking-neuron geometry. Networks of SVM neurons offer advantages of speed and computational efficiency, relative to traditional artificial neural networks. The SVM also overcomes some of the limitations of prior spiking-neuron models. There are numerous potential pattern-recognition, tracking, and data-reduction (data preprocessing) applications for these SVM neural networks on Earth and in exploration of remote planets. Spiking neurons imitate biological neurons more closely than do the neurons of traditional artificial neural networks. A spiking neuron includes a central cell body (soma) surrounded by a tree-like interconnection network (dendrites). Spiking neurons are so named because they generate trains of output pulses (spikes) in response to inputs received from sensors or from other neurons. They gain their speed advantage over traditional neural networks by using the timing of individual spikes for computation, whereas traditional artificial neurons use averages of activity levels over time. Moreover, spiking neurons use the delays inherent in dendritic processing in order to efficiently encode the information content of incoming signals. Because traditional artificial neurons fail to capture this encoding, they have less processing capability, and so it is necessary to use more gates when implementing traditional artificial neurons in electronic circuitry. Such higher-order functions as dynamic tasking are effected by use of pools (collections) of spiking neurons interconnected by spike-transmitting fibers. The SVM includes adaptive thresholds and submodels of transport of ions (in imitation of such transport in biological

  2. Peptides and the new endocrinology

    NASA Astrophysics Data System (ADS)

    Schwyzer, Robert

    1982-01-01

    The discovery of regulatory peptides common to the nervous and the endocrine systems (brain, gut, and skin) has brought about a revolution in our concepts of endocrinology and neurology. We are beginning to understand some of the complex interrelationships between soma and psyche that might, someday, be important for an integrated treatment of diseases. Examples of the actions of certain peptides in the periphery and in the central nervous system are given, and their biosynthesis and molecular anatomy as carriers for information are discussed.

  3. Influence of asymmetric attenuation of single and paired dendritic inputs on summation of synaptic potentials and initiation of action potentials.

    PubMed

    Fortier, Pierre A; Bray, Chelsea

    2013-04-16

    Previous studies revealed mechanisms of dendritic inputs leading to action potential initiation at the axon initial segment and backpropagation into the dendritic tree. This interest has recently expanded toward the communication between different parts of the dendritic tree which could preprocess information before reaching the soma. This study tested for effects of asymmetric voltage attenuation between different sites in the dendritic tree on summation of synaptic inputs and action potential initiation using the NEURON simulation environment. Passive responses due to the electrical equivalent circuit of the three-dimensional neuron architecture with leak channels were examined first, followed by the responses after adding voltage-gated channels and finally synaptic noise. Asymmetric attenuation of voltage, which is a function of asymmetric input resistance, was seen between all pairs of dendritic sites but the transfer voltages (voltage recorded at the opposite site from stimulation among a pair of dendritic sites) were equal and also summed linearly with local voltage responses during simultaneous stimulation of both sites. In neurons with voltage-gated channels, we reproduced the observations where a brief stimulus to the proximal ascending dendritic branch of a pyramidal cell triggers a local action potential but a long stimulus triggers a somal action potential. Combined stimulation of a pair of sites in this proximal dendrite did not alter this pattern. The attraction of the action potential onset toward the soma with a long stimulus in the absence of noise was due to the higher density of voltage-gated sodium channels at the axon initial segment. This attraction was, however, negligible at the most remote distal dendritic sites and was replaced by an effect due to high input resistance. Action potential onset occurred at the dendritic site of higher input resistance among a pair of remote dendritic sites, irrespective of which of these two sites received

  4. Dynamics of neurons controlling movements of a locust hind leg. III. Extensor tibiae motor neurons.

    PubMed

    Newland, P L; Kondoh, Y

    1997-06-01

    Imposed movements of the apodeme of the femoral chordotonal organ (FeCO) of the locust hind leg elicit resistance reflexes in extensor and flexor tibiae motor neurons. The synaptic responses of the fast and slow extensor tibiae motor neurons (FETi and SETi, respectively) and the spike responses of SETi were analyzed with the use of the Wiener kernel white noise method to determine their response properties. The first-order Wiener kernels computed from soma recordings were essentially monophasic, or low passed, indicating that the motor neurons were primarily sensitive to the position of the tibia about the femorotibial joint. The responses of both extensor motor neurons had large nonlinear components. The second-order kernels of the synaptic responses of FETi and SETi had large on-diagonal peaks with two small off-diagonal valleys. That of SETi had an additional elongated valley on the diagonal, which was accompanied by two off-diagonal depolarizing peaks at a cutoff frequency of 58 Hz. These second-order components represent a half-wave rectification of the position-sensitive depolarizing response in FETi and SETi, and a delayed inhibitory input to SETi, indicating that both motor neurons were directionally sensitive. Model predictions of the responses of the motor neurons showed that the first-order (linear) characterization poorly predicted the actual responses of FETi and SETi to FeCO stimulation, whereas the addition of the second-order (nonlinear) term markedly improved the performance of the model. Simultaneous recordings from the soma and a neuropilar process of FETi showed that its synaptic responses to FeCO stimulation were phase delayed by about -30 degrees at 20 Hz, and reduced in amplitude by 30-40% when recorded in the soma. Similar configurations of the first and second-order kernels indicated that the primary process of FETi acted as a low-pass filter. Cross-correlation between a white noise stimulus and a unitized spike discharge of SETi again

  5. Identification of Genes Uniquely Expressed in the Germ-Line Tissues of the Jewel Wasp Nasonia vitripennis

    PubMed Central

    Ferree, Patrick M.; Fang, Christopher; Mastrodimos, Mariah; Hay, Bruce A.; Amrhein, Henry; Akbari, Omar S.

    2015-01-01

    The jewel wasp Nasonia vitripennis is a rising model organism for the study of haplo-diploid reproduction characteristic of hymenopteran insects, which include all wasps, bees, and ants. We performed transcriptional profiling of the ovary, the female soma, and the male soma of N. vitripennis to complement a previously existing transcriptome of the wasp testis. These data were deposited into an open-access genome browser for visualization of transcripts relative to their gene models. We used these data to identify the assemblies of genes uniquely expressed in the germ-line tissues. We found that 156 protein-coding genes are expressed exclusively in the wasp testis compared with only 22 in the ovary. Of the testis-specific genes, eight are candidates for male-specific DNA packaging proteins known as protamines. We found very similar expression patterns of centrosome associated genes in the testis and ovary, arguing that de novo centrosome formation, a key process for development of unfertilized eggs into males, likely does not rely on large-scale transcriptional differences between these tissues. In contrast, a number of meiosis-related genes show a bias toward testis-specific expression, despite the lack of true meiosis in N. vitripennis males. These patterns may reflect an unexpected complexity of male gamete production in the haploid males of this organism. Broadly, these data add to the growing number of genomic and genetic tools available in N. vitripennis for addressing important biological questions in this rising insect model organism. PMID:26464360

  6. Neuron-to-neuron transmission of α-synuclein fibrils through axonal transport

    PubMed Central

    Freundt, Eric C.; Maynard, Nate; Clancy, Eileen K.; Roy, Shyamali; Bousset, Luc; Sourigues, Yannick; Covert, Markus; Melki, Ronald; Kirkegaard, Karla; Brahic, Michel

    2012-01-01

    Objective The lesions of Parkinson's disease spread through the brain in a characteristic pattern that corresponds to axonal projections. Previous observations suggest that misfolded α-synuclein could behave as a prion, moving from neuron to neuron and causing endogenous α-synuclein to misfold. Here, we characterized and quantified the axonal transport of α-synuclein fibrils and showed that fibrils could be transferred from axons to second-order neurons following anterograde transport. Methods We grew primary cortical mouse neurons in microfluidic devices to separate soma from axonal projections in fluidically isolated microenvironments. We used live-cell imaging and immunofluorescence to characterize the transport of fluorescent α-synuclein fibrils and their transfer to second-order neurons. Results Fibrillar α-synuclein was internalized by primary neurons and transported in axons with kinetics consistent with slow component-b of axonal transport (fast axonal transport with saltatory movement). Fibrillar α-synuclein was readily observed in the cell bodies of second-order neurons following anterograde axonal transport. Axon-to-soma transfer appeared not to require synaptic contacts. Interpretation These results support the hypothesis that the progression of Parkinson's disease can be caused by neuron-to-neuron spread of α-synuclein aggregates and that the anatomical pattern of progression of lesions between axonally connected areas results from the axonal transport of such aggregates. That the transfer did not appear to be transsynaptic gives hope that α-synuclein fibrils could be intercepted by drugs during the extra-cellular phase of their journey. PMID:23109146

  7. The strain-encoded relationship between PrP replication, stability and processing in neurons is predictive of the incubation period of disease.

    PubMed

    Ayers, Jacob I; Schutt, Charles R; Shikiya, Ronald A; Aguzzi, Adriano; Kincaid, Anthony E; Bartz, Jason C

    2011-03-01

    Prion strains are characterized by differences in the outcome of disease, most notably incubation period and neuropathological features. While it is established that the disease specific isoform of the prion protein, PrP(Sc), is an essential component of the infectious agent, the strain-specific relationship between PrP(Sc) properties and the biological features of the resulting disease is not clear. To investigate this relationship, we examined the amplification efficiency and conformational stability of PrP(Sc) from eight hamster-adapted prion strains and compared it to the resulting incubation period of disease and processing of PrP(Sc) in neurons and glia. We found that short incubation period strains were characterized by more efficient PrP(Sc) amplification and higher PrP(Sc) conformational stabilities compared to long incubation period strains. In the CNS, the short incubation period strains were characterized by the accumulation of N-terminally truncated PrP(Sc) in the soma of neurons, astrocytes and microglia in contrast to long incubation period strains where PrP(Sc) did not accumulate to detectable levels in the soma of neurons but was detected in glia similar to short incubation period strains. These results are inconsistent with the hypothesis that a decrease in conformational stability results in a corresponding increase in replication efficiency and suggest that glia mediated neurodegeneration results in longer survival times compared to direct replication of PrP(Sc) in neurons.

  8. In Situ Proximity Ligation Assay Reveals Co-Localization of Alpha-Synuclein and SNARE Proteins in Murine Primary Neurons.

    PubMed

    Almandoz-Gil, Leire; Persson, Emma; Lindström, Veronica; Ingelsson, Martin; Erlandsson, Anna; Bergström, Joakim

    2018-01-01

    The aggregation of alpha-synuclein (αSyn) is the pathological hallmark of Parkinson's disease, dementia with Lewy bodies and related neurological disorders. However, the physiological function of the protein and how this function relates to its pathological effects remain poorly understood. One of the proposed roles of αSyn is to promote the soluble N -ethylmaleimide-sensitive factor attachment protein receptor (SNARE) complex assembly by binding to VAMP-2. The objective of this study was to visualize the co-localization between αSyn and the SNARE proteins (VAMP-2, SNAP-25, and syntaxin-1) for the first time using in situ proximity ligation assay (PLA). Cortical primary neurons were cultured from either non-transgenic or transgenic mice expressing human αSyn with the A30P mutation under the Thy-1 promoter. With an antibody recognizing both mouse and human αSyn, a PLA signal indicating close proximity between αSyn and the three SNARE proteins was observed both in the soma and throughout the processes. No differences in the extent of PLA signals were seen between non-transgenic and transgenic neurons. With an antibody specific against human αSyn, the PLA signal was mostly located to the soma and was only present in a few cells. Taken together, in situ PLA is a method that can be used to investigate the co-localization of αSyn and the SNARE proteins in primary neuronal cultures.

  9. Distribution and structure of efferent synapses in the chicken retina

    PubMed Central

    Lindstrom, SH; Nacsa, N; Blankenship, T; Fitzgerald, PG; Weller, C; Vaney, DI; Wilson, M

    2012-01-01

    The visual system of birds includes an efferent projection from a visual area, the isthmooptic nucleus in the midbrain, back to the retina. Using a combination of anterograde labeling of efferent fibers, reconstruction of dye-filled neurons, NADPH-diaphorase staining, and transmission electron microscopy we have examined the distribution of efferent fibers and their synaptic structures in the chicken retina. We show that efferent fibers terminate strictly within the ventral retina. In 2 completely mapped retinas, only 2 fibers from a total of 15,359 terminated in the dorsal retina. The major synapse made by each efferent fiber is with a single Efferent Target Amacrine Cell (TC). This synapse consists of 5-25 boutons of 2μm diameter, each with multiple active zones, pressed into the TC soma or synapsing with a basketwork of rudimentary TC dendrites in the inner nuclear layer (INL). This basketwork, which is sheathed by Muller cells processes, defines a private neuropil in the INL within which TCs were also seen to receive input from retinal neurons. In addition to the major synapse, efferent fibers typically produce several very thin processes that terminate nearby in single small boutons and for which the soma of a local amacrine cell is one of the likely postsynaptic partners. A minority of efferent fibers also give rise to a thicker process terminating in a strongly diaphorase positive ball about 5μm in diameter. PMID:19439107

  10. Electric potentiation of gravikinesis in Paramecium is possibly mediated by filaments.

    PubMed

    Machemer, H

    1998-01-01

    Sensitivity of Paramecium to mechanical stress including gravitational force is organized along two opposing gradients of membrane channel distribution: depolarizing Ca channels and hyperpolarizing K channels. Mechanoreceptor channels reside in the membrane of the cell soma and are activated, when the weight of the cytoplasm deforms the "lower" plasma membrane. Channel distribution is such as to generate ciliary activation which can counteract sedimentation of the cells: a reduction in downward swimming rate and an augmentation in upward swimming rate. Application of weak DC fields does not only induce the well-known cathodal orientation and swimming of Paramecium toward the cathode (galvano-taxis). We document that swimming velocity is augmented up to 175% as a function of the voltage gradient between 0.3 V/cm and 0.8 V/cm (galvanokinesis). A gradient of 0.3 V/cm was highly effective in raising the common negative gravikinesis of downward swimmers threefold. The gravikinesis of upward swimmers reversed polarity under field stimulation inducing cells to augment sedimentation effects (positive gravikinesis). Both effects of electric-field stimulation on ciliary activation are of the depolarizing type: reduction in the frequency of normally beating cilia. Analysis of the data shows that a voltage-sensitivity of gravireceptor channels would not account for the observed potentiation of negative gravikinesis. It is suggested that a previously described voltage-dependent Ca channel of the soma membrane interferes with a Ca(2+)-sensitive, peripheral filament system, which directly connects to gravireceptor channels.

  11. Homozygous SLC6A17 Mutations Cause Autosomal-Recessive Intellectual Disability with Progressive Tremor, Speech Impairment, and Behavioral Problems

    PubMed Central

    Iqbal, Zafar; Willemsen, Marjolein H.; Papon, Marie-Amélie; Musante, Luciana; Benevento, Marco; Hu, Hao; Venselaar, Hanka; Wissink-Lindhout, Willemijn M.; Vulto-van Silfhout, Anneke T.; Vissers, Lisenka E.L.M.; de Brouwer, Arjan P.M.; Marouillat, Sylviane; Wienker, Thomas F.; Ropers, Hans Hilger; Kahrizi, Kimia; Nadif Kasri, Nael; Najmabadi, Hossein; Laumonnier, Frédéric; Kleefstra, Tjitske; van Bokhoven, Hans

    2015-01-01

    We report on Dutch and Iranian families with affected individuals who present with moderate to severe intellectual disability and additional phenotypes including progressive tremor, speech impairment, and behavioral problems in certain individuals. A combination of exome sequencing and homozygosity mapping revealed homozygous mutations c.484G>A (p.Gly162Arg) and c.1898C>G (p.Pro633Arg) in SLC6A17. SLC6A17 is predominantly expressed in the brain, encodes a synaptic vesicular transporter of neutral amino acids and glutamate, and plays an important role in the regulation of glutamatergic synapses. Prediction programs and 3D modeling suggest that the identified mutations are deleterious to protein function. To directly test the functional consequences, we investigated the neuronal subcellular localization of overexpressed wild-type and mutant variants in mouse primary hippocampal neuronal cells. Wild-type protein was present in soma, axons, dendrites, and dendritic spines. p.Pro633Arg altered SLC6A17 was found in soma and proximal dendrites but did not reach spines. p.Gly162Arg altered SLC6A17 showed a normal subcellular distribution but was associated with an abnormal neuronal morphology mainly characterized by the loss of dendritic spines. In summary, our genetic findings implicate homozygous SLC6A17 mutations in autosomal-recessive intellectual disability, and their pathogenic role is strengthened by genetic evidence and in silico and in vitro functional analyses. PMID:25704603

  12. Statistical analysis of dendritic spine distributions in rat hippocampal cultures

    PubMed Central

    2013-01-01

    Background Dendritic spines serve as key computational structures in brain plasticity. Much remains to be learned about their spatial and temporal distribution among neurons. Our aim in this study was to perform exploratory analyses based on the population distributions of dendritic spines with regard to their morphological characteristics and period of growth in dissociated hippocampal neurons. We fit a log-linear model to the contingency table of spine features such as spine type and distance from the soma to first determine which features were important in modeling the spines, as well as the relationships between such features. A multinomial logistic regression was then used to predict the spine types using the features suggested by the log-linear model, along with neighboring spine information. Finally, an important variant of Ripley’s K-function applicable to linear networks was used to study the spatial distribution of spines along dendrites. Results Our study indicated that in the culture system, (i) dendritic spine densities were "completely spatially random", (ii) spine type and distance from the soma were independent quantities, and most importantly, (iii) spines had a tendency to cluster with other spines of the same type. Conclusions Although these results may vary with other systems, our primary contribution is the set of statistical tools for morphological modeling of spines which can be used to assess neuronal cultures following gene manipulation such as RNAi, and to study induced pluripotent stem cells differentiated to neurons. PMID:24088199

  13. Ultrastructure of cholinergic neurons in the laterodorsal tegmental nucleus of the rat: interaction with catecholamine fibers.

    PubMed

    Kubota, Y; Leung, E; Vincent, S R

    1992-01-01

    The ultrastructure of choline acetyltransferase (ChAT)-immunoreactive neurons in the laterodorsal tegmental nucleus (TLD) of the rat was investigated by immunohistochemical techniques. The immunoreactive neurons were medium to large in size, with a few elongated dendrites, contained well-developed cytoplasm, and a nucleus with deep infoldings. They received many nonimmunoreactive, mostly asymmetric synaptic inputs on their soma and dendrites. ChAT-immunoreactive, usually myelinated, axons were occasionally seen in TLD. Only one immunoreactive axon terminal was observed within TLD, and it made synaptic contact with a nonimmunoreactive neuronal perikaryon. The synaptic interactions between ChAT-immunoreactive neurons and tyrosine hydroxylase (TH)-immunoreactive fibers in the TLD were investigated with a double immunohistochemical staining method. ChAT-immunoreactivity detected with a beta-galactosidase method was light blue-green in the light microscope and formed dot-like electron dense particles at the electron microscopic level. TH-immunoreactivity, visualized with a nickel-enhanced immunoperoxidase method, was dark blue-black in the light microscope and diffusely opaque in the electron microscope. Therefore, the difference between these two kinds of immunoreactivity could be quite easily distinguished at both light and electron microscopic levels. In the light microscope, TH-positive fibers were often closely apposed to ChAT-immunoreactive cell bodies and dendrites in TLD. In the electron microscope, the cell soma and proximal dendrites of ChAT-immunoreactive neurons received synaptic contacts from TH-immunoreactive axon terminals. These results provide a morphological basis for catecholaminergic regulation of the cholinergic reticular system.

  14. Mental Health Crisis in Northeast Fukushima after the 2011 Earthquake, Tsunami and Nuclear Disaster.

    PubMed

    Fukunaga, Hisanori; Kumakawa, Hiromi

    2015-09-01

    The great earthquake of 11 March 2011 and resulting tsunami caused serious damage to various areas of the Pacific coast in northeast Fukushima, and all the residents faced fears of meltdown of the reactors at the Fukushima Daiichi Nuclear Power Plant. One of the most seriously affected areas was the district of Soso, located in the northeast part of Fukushima prefecture, with 12 municipalities (Soma City, Minamisoma City, Shinchi Town, Namie Town, Futaba Town, Ōkuma Town, Tomioka Town, Naraha Town, Hirono Town, Iitate Village, Katsurao Village and Kawauchi Village). The district of Soso is home to approximately 200,000 residents, many of whom were seriously affected by the threefold disaster. During the subsequent four years, the population of Soso decreased by nearly 10%. In March 2011 before the disaster, five hospitals and two clinics for psychiatric patients, along with 712 inpatients, were operating in the district of Soso. However, as of March 2015, there were only one hospital and three clinics, along with approximately 50 inpatients, although a new mental health clinic in Soma City was opened in 2012 for supporting victims suffering from the disaster. We hereby suggest that the patients and residents of northeast Fukushima may be undergoing mental health crisis. In fact, disaster-related psychological stress could have induced several physical and mental disorders. The mid- and long-term supports are urgently needed not only for psychiatric patients but also for all residents in the district of Soso.

  15. Tracking the Fragile X Mental Retardation Protein in a Highly Ordered Neuronal RiboNucleoParticles Population: A Link between Stalled Polyribosomes and RNA Granules.

    PubMed

    El Fatimy, Rachid; Davidovic, Laetitia; Tremblay, Sandra; Jaglin, Xavier; Dury, Alain; Robert, Claude; De Koninck, Paul; Khandjian, Edouard W

    2016-07-01

    Local translation at the synapse plays key roles in neuron development and activity-dependent synaptic plasticity. mRNAs are translocated from the neuronal soma to the distant synapses as compacted ribonucleoparticles referred to as RNA granules. These contain many RNA-binding proteins, including the Fragile X Mental Retardation Protein (FMRP), the absence of which results in Fragile X Syndrome, the most common inherited form of intellectual disability and the leading genetic cause of autism. Using FMRP as a tracer, we purified a specific population of RNA granules from mouse brain homogenates. Protein composition analyses revealed a strong relationship between polyribosomes and RNA granules. However, the latter have distinct architectural and structural properties, since they are detected as close compact structures as observed by electron microscopy, and converging evidence point to the possibility that these structures emerge from stalled polyribosomes. Time-lapse video microscopy indicated that single granules merge to form cargoes that are transported from the soma to distal locations. Transcriptomic analyses showed that a subset of mRNAs involved in cytoskeleton remodelling and neural development is selectively enriched in RNA granules. One third of the putative mRNA targets described for FMRP appear to be transported in granules and FMRP is more abundant in granules than in polyribosomes. This observation supports a primary role for FMRP in granules biology. Our findings open new avenues for the study of RNA granule dysfunctions in animal models of nervous system disorders, such as Fragile X syndrome.

  16. Different kinetic properties of two T-type Ca2+ currents of rat reticular thalamic neurones and their modulation by enflurane

    PubMed Central

    Joksovic, Pavle M; Bayliss, Douglas A; Todorovic, Slobodan M

    2005-01-01

    Currents arising from T-type Ca2+ channels in nucleus reticularis thalami (nRT) play a critical role in generation of low-amplitude oscillatory bursting involving mutually interconnected cortical and thalamic neurones, and are implicated in the state of arousal and sleep, as well as seizures. Here we show in brain slices from young rats that two kinetically different T-type Ca2+ currents exist in nRT neurones, with a slowly inactivating current expressed only on proximal dendrites, and fast inactivating current predominantly expressed on soma. Nickel was about twofold more potent in blocking fast (IC50 64 μm) than slow current (IC50 107 μm). The halogenated volatile anaesthetic enflurane blocked both currents, but only the slowly inactivating current was affected in voltage-dependent fashion. Slow dendritic current was essential for generation of low-threshold Ca2+ spikes (LTS), and both enflurane and nickel also suppressed LTS and neuronal burst firing at concentrations that blocked isolated T currents. Differential kinetic properties of T currents expressed in cell soma and proximal dendrites of nRT neurones indicate that various subcellular compartments may exhibit different membrane properties in response to small membrane depolarizations. Furthermore, since blockade of two different T currents in nRT neurones by enflurane and other volatile anaesthetics occurs within concentrations that are relevant during clinical anaesthesia, our findings suggest that these actions could contribute to some important clinical effects of anaesthetics. PMID:15845580

  17. Molecular analysis of ivy cells of the hippocampal CA1 stratum radiatum using spectral identification of immunofluorophores

    PubMed Central

    Somogyi, Jozsef; Szabo, Andras; Somogyi, Peter; Lamsa, Karri

    2012-01-01

    Neuronal nitric oxide synthase-expressing (nNOS+) GABAergic interneurons are common in hippocampal stratum (str.) radiatum. However, these cells are less well characterized than nNOS+ ivy cells in str. pyramidale or neurogliaform cells (NGC) in str. lacunosum-moleculare. Here we have studied the laminar distribution of the axons and dendrites, and the immunoreactivity of these neurons recorded in rat hippocampal slices. We have used spectral analysis of antibody- or streptavidin-conjugated fluorophores to improve recognition of genuine signals in reactions for molecules such as nNOS and neuropeptide-Y (NPY). We found that most nNOS+ cells with soma in the CA1 area str. radiatum exhibit characteristic properties of ivy cells, and were positive for NPY and negative for reelin. However, laminar distributions of their neurites differ from original characterization of ivy cells with the soma in or close to str. pyramidale. Both their dendrites and axon are mainly in str. radiatum and to a lesser extent in str. oriens, and in addition often extend to str. lacunosum-moleculare. We conclude that ivy cells in str. radiatum may predominantly be feedforward inhibitory interneurons in the CA1 area, and their axonal output delivering GABA, NPY, and NO can influence both the entorhinal cortex innervated and the CA3 innervated zones pre- and post-synaptically. Spectral analysis of fluorophores provides an objective algorithm to analyze signals in immunoreactions for neurochemical markers. PMID:22666191

  18. The beneficial effects of treadmill step training on activity-dependent synaptic and cellular plasticity markers after complete spinal cord injury.

    PubMed

    Ilha, Jocemar; Centenaro, Lígia A; Broetto Cunha, Núbia; de Souza, Daniela F; Jaeger, Mariane; do Nascimento, Patrícia S; Kolling, Janaína; Ben, Juliana; Marcuzzo, Simone; Wyse, Angela T S; Gottfried, Carmem; Achaval, Matilde

    2011-06-01

    Several studies have shown that treadmill training improves neurological outcomes and promotes plasticity in lumbar spinal cord of spinal animals. The morphological and biochemical mechanisms underlying these phenomena remain unclear. The purpose of this study was to provide evidence of activity-dependent plasticity in spinal cord segment (L5) below a complete spinal cord transection (SCT) at T8-9 in rats in which the lower spinal cord segments have been fully separated from supraspinal control and that subsequently underwent treadmill step training. Five days after SCT, spinal animals started a step-training program on a treadmill with partial body weight support and manual step help. Hindlimb movements were evaluated over time and scored on the basis of the open-field BBB scale and were significantly improved at post-injury weeks 8 and 10 in trained spinal animals. Treadmill training also showed normalization of withdrawal reflex in trained spinal animals, which was significantly different from the untrained animals at post-injury weeks 8 and 10. Additionally, compared to controls, spinal rats had alpha motoneuronal soma size atrophy and reduced synaptophysin protein expression and Na(+), K(+)-ATPase activity in lumbar spinal cord. Step-trained rats had motoneuronal soma size, synaptophysin expression and Na(+), K(+)-ATPase activity similar to control animals. These findings suggest that treadmill step training can promote activity-dependent neural plasticity in lumbar spinal cord, which may lead to neurological improvements without supraspinal descending control after complete spinal cord injury.

  19. Response to Comment on "Active sites for CO2 hydrogenation to methanol on Cu/ZnO catalysts".

    PubMed

    Kattel, Shyam; Ramírez, Pedro J; Chen, Jingguang G; Rodriguez, José A; Liu, Ping

    2017-09-01

    In their Comment on the our recent Report, Nakamura et al argue that our x-ray photoelectron spectroscopy (XPS) analysis was affected by the presence of formate species on the catalyst surface. This argument is not valid because the reactant gases were evacuated at temperatures from 525 to 575 kelvin, conditions under which formate is not stable on the catalyst surface. An analysis of the XPS results obtained after exposing zinc oxide/copper (111) [ZnO/Cu(111)] surfaces to hydrogen (H 2 ) and mixtures of carbon dioxide (CO 2 )/H 2 show an absence of carbon (C) 1s signal, no asymmetries in the oxygen (O) 1s peak, and a Zn:O intensity close to 1:1. Thus, the most active phase of these catalysts contained a ZnO-Cu interface. Copyright © 2017, American Association for the Advancement of Science.

  20. Immunochemical detection of food-derived isothiocyanate as a lysine conjugate.

    PubMed

    Nakamura, Toshiyuki; Kitamoto, Noritoshi; Osawa, Toshihiko; Kato, Yoji

    2010-01-01

    In a previous study we prepared monoclonal antibody against allyl isothiocyanate (AITC)-modified lysine (Lys), and found that AITC reacted with Lys under physiological conditions in vitro (T. Nakamura et al., Chem. Res. Toxicol., 22, 536-542 (2009)). In the present study, antibodies against benzyl isothiocyanate (ITC), 6-methylsulfinylhexyl ITC and phenethyl ITC modified protein were prepared, and the respective monoclonal antibodies, B6C9, 6MS3D10, and PE3A10 were obtained. These antibodies were applied to ITC detection in food using shredded Wasabia japonica (wasabi) and ground Carica papaya (papaya) seed by trapping ITC with biotin-labeled bovine serum albumin. ITC formation from the wasabi and papaya seed samples was confirmed using the antibodies in a dose-dependent manner. These antibodies might be applicable in identifying food-derived ITC.

  1. Response to Comment on “Active sites for CO 2 hydrogenation to methanol on Cu/ZnO catalysts”

    DOE PAGES

    Kattel, Shyam; Ramírez, Pedro J.; Chen, Jingguang G.; ...

    2017-09-01

    In their Comment on our recent paper, Nakamura et al. argue that our x-ray photoelectron spectroscopy (XPS) analysis was affected by the presence of formate species on the catalyst surface. This argument is not valid because the reactant gases were evacuated at temperatures from 525 to 575 kelvin, conditions under which formate is not stable on the catalyst surface. An analysis of the XPS results obtained after exposing zinc oxide/copper (111) [ZnO/Cu(111)] surfaces to hydrogen (H 2) and mixtures of carbon dioxide (CO 2)/H 2 show an absence of carbon (C) 1s signal, no asymmetries in the oxygen (O) 1smore » peak, and a Zn:O intensity close to 1:1. Thus and finally, the most active phase of these catalysts contained a ZnO-Cu interface.« less

  2. Measurement Theory Based on the Truth Values Violates Local Realism

    NASA Astrophysics Data System (ADS)

    Nagata, Koji

    2017-02-01

    We investigate the violation factor of the Bell-Mermin inequality. Until now, we use an assumption that the results of measurement are ±1. In this case, the maximum violation factor is 2( n-1)/2. The quantum predictions by n-partite Greenberger-Horne-Zeilinger (GHZ) state violate the Bell-Mermin inequality by an amount that grows exponentially with n. Recently, a new measurement theory based on the truth values is proposed (Nagata and Nakamura, Int. J. Theor. Phys. 55:3616, 2016). The values of measurement outcome are either +1 or 0. Here we use the new measurement theory. We consider multipartite GHZ state. It turns out that the Bell-Mermin inequality is violated by the amount of 2( n-1)/2. The measurement theory based on the truth values provides the maximum violation of the Bell-Mermin inequality.

  3. Creating understanding of reproductive health. Exchanges.

    PubMed

    1997-02-01

    Yoko Komiyama, senior commentator of the Japan Broadcasting Corporation; Miyuki Nakamura, senior staff writer of Nihon Keizai Shimbun's Lifestyle News Department; and Miki Morimoto, staff writer for the Center for Research and Analysis on Global Issues Project 21, Asahi Shimbun, were introduced to population and reproductive health issues and the situation of women in Nepal during a December 8-16 interregional study tour. JOICFP selected the participants and organized an itinerary which provided insights into multilateral cooperation between UNFPA and the Ministry of Health (MOH) of Nepal, bilateral assistance between the Japan International Cooperation Agency and MOH, and nongovernmental organization collaboration between the Family Planning Association of Nepal and JOICFP. Upon returning to Japan, these representatives of three of Japan's major mass media groups shared their experiences with the general public through reports in newspapers, and on radio and television.

  4. Psyche, soma, and science studies: new directions in the sociology of mental health and illness.

    PubMed

    Pickersgill, Martyn D

    2010-08-01

    With the expanding scope of scientific and technological discourse within psychiatry, social scientists need new theoretical tools to grapple with the complex links between psychiatry, science and society. Benefit may be afforded through engagement with the discipline of science and technology studies (STS), which is concerned explicitly with the relationships between science and society. To highlight existing engagements between STS and the sociology of (mental) health, and to encourage researchers to consider ways in which insights from these traditions may be developed further through interdisciplinary debate and analysis. Some of the key works in STS and the sociology of mental illness that use the empirical or theoretical writings of the other were reviewed and appraised. Whilst it is clear that some research synthesizing insights from STS and the sociology of mental health exists, this is currently limited. Sociologists and others concerned with longstanding and emergent issues in mental health might usefully familiarize themselves with some work in STS. A new sociology of psychiatric knowledge production and application represents an important way forward.

  5. VizieR Online Data Catalog: SOFIA Massive (SOMA) Star Formation Survey. I. (De Buizer+, 2017)

    NASA Astrophysics Data System (ADS)

    De Buizer, J. M.; Liu, M.; Tan, J. C.; Zhang, Y.; Beltran, M. T.; Shuping, R.; Staff, J. E.; Tanaka, K. E. I.; Whitney, B.

    2018-02-01

    The following eight sources, AFGL 4029, AFGL 437, IRAS 07299-1651, G35.20-0.74, G45.45+0.05, IRAS 20126+4104, Cepheus A, and NGC 7538 IRS9, were observed by SOFIA with the FORCAST instrument (see Table 1). Data were taken on multiple flights spanning the Early Science period, Cycle 1, and Cycle 2 SOFIA observing cycles (spanning 2011 May to 2014 June). (4 data files).

  6. Characteristics of receptor- and transducer-coupled activation of the intracellular signalling in sensory neuron revealed by atomic force microscopy

    NASA Astrophysics Data System (ADS)

    Khalisov, M. M.; Penniyaynen, V. A.; Esikova, N. A.; Ankudinov, A. V.; Krylov, B. V.

    2017-01-01

    The mechanical properties of sensory neurons upon activation of intracellular cascade processes by comenic acid binding to a membrane opioid-like receptor (receptor-coupled), as well as a very low (endogenous) concentration of ouabain (transducer-coupled), have been investigated. Using atomic force microscopy, it is established that exposure to ouabain, in contrast to the impact of comenic acid, leads to a hardening of the neuron soma. This suggests that the receptor-coupled signal transmission to the cell genome is carried out through mechanisms that are different from the transducer-coupled signal pathways.

  7. Teacher ratings of resilience and peer relationships of preschoolers whose fathers died unexpectedly.

    PubMed

    Gülay Ogelman, Hülya; Gündoğan, Aysun; Erten Sarıkaya, Hatice; Erol, Ahmet

    2016-08-01

    This study endeavors to compare resilience and peer relationships of children who lost their fathers in a major mining accident in Soma with those who did not. Teachers rated 51 preschoolers whose fathers died, and 53 preschoolers whose fathers were alive. On the negative side, bereaved children had lower resilience and higher exclusion; on the positive side, bereaved children had lower peer victimization and higher prosocial behavior. Death of fathers is associated with lower resilience and more exclusion among young children, but others treat them better as well.

  8. The Justifications for War and Peace in World Religions: Part II: Extracts, Summaries and Comparisons of Scriptures in Indic Religions (Buddhism, Hinduism, Jainism and Sikhism)

    DTIC Science & Technology

    2010-04-01

    the Brâhmana caste (though he has not studied the Veda or been initiated for a Soma-sacrifice), 8. Likewise he who has destroyed an embryo of a...king, they are obedient and act only on the orders of another. 31. “It is as a consequence of my evil destiny and my own misdeeds in the past that I...heavenly planets” (6.11.4). To kill a brahmana who is a saintly and sinless person, versed in Vedic knowledge, would be “like destroying the embryo

  9. Pitch Angle Scattering of Energetic Electrons by Plasmaspheric Hiss Emissions

    NASA Astrophysics Data System (ADS)

    Tobita, M.; Omura, Y.; Summers, D.

    2017-12-01

    We study scattering of energetic electrons in pitch angles and kinetic energies through their resonance with plasmaspheric hiss emissions consisting of many coherent discrete whistler-mode wave packets with rising and falling frequencies [1,2,3]. Using test particle simulations, we evaluate the efficiency of scattering, which depends on the inhomogeneity ratio S of whistler mode wave-particle interaction [4]. The value of S is determined by the wave amplitude, frequency sweep rate, and the gradient of the background magnetic field. We first modulate those parameters and observe variations of pitch angles and kinetic energies of electrons with a single wave under various S values so as to obtain basic understanding. We then include many waves into the system to simulate plasmaspheric hiss emissions. As the wave packets propagate away from the magnetic equator, the nonlinear trapping potential at the resonance velocity is deformed, making a channel of gyrophase for untrapped electrons to cross the resonance velocity, and causing modulations in their pitch angles and kinetic energies. We find efficient scattering of pitch angles and kinetic energies because of coherent nonlinear wave-particle interaction, resulting in electron precipitations into the polar atmosphere. We compare the results with the bounce averaged pitch angle diffusion coefficient based on quasi-linear theory, and show that the nonlinear wave model with many coherent packets can cause scattering of resonant electrons much faster than the quasi-linear diffusion process. [1] Summers, D., Omura, Y., Nakamura, S., and C. A. Kletzing (2014), Fine structure of plasmaspheric hiss, J. Geophys. Res., 119, 9134-9149. [2] Omura, Y., Y. Miyashita, M. Yoshikawa, D. Summers, M. Hikishima, Y. Ebihara, and Y. Kubota (2015), Formation process of relativistic electron flux through interaction with chorus emissions in the Earth's inner magnetosphere, J. Geophys. Res. Space Physics, 120, 9545-9562. [3] Nakamura, S., Y

  10. PREFACE: International Symposium "Nanoscience and Quantum Physics 2011" (nanoPHYS'11)

    NASA Astrophysics Data System (ADS)

    Saito, Susumu; Tanaka, Hidekazu; Nakamura, Takashi; Nakamura, Masaaki

    2011-07-01

    authors, the referees, and all the individuals involved in the symposium organization, in particular, all the committee members and secretaries who helped to make this symposium so successful. The organizing committee would like to take this opportunity to thank the invited speakers, the session chairs, and all the attendees for their contribution to the symposium. Susumu Saito, Hidekazu Tanaka, Takashi Nakamura and Masaaki Nakamura, Editors Conference photograph

  11. Extreme QCD 2012 (xQCD)

    NASA Astrophysics Data System (ADS)

    2013-04-01

    Acknowledgements This conference would not have been possible without the generous support from Brookhaven National Laboratory and the George Washington University INS and IMPACT institutes, Columbian College of Arts and Sciences, the Office of Vice-President for Research, and the Department of Physics. We thank them wholeheartedly. We are also very grateful for the support of our colleagues on the local organizing committee, Walter Freeman and Frank Lee, and on the International Advisory Committee: Simon Hands, Tetsuo Hatsuda, Frithjof Karsch, Maria Paola Lombardo, Tereza Mendes, Atsushi Nakamura, Owe Philipsen, Claudia Ratti, Paul Romatschke, Misha Stephanov, and Nu Xu. List of participants Alexandru, Andrei George Washington University Bazavov, Alexei Brookhaven National Laboratory Bloch, Jacques University of Regensburg Braun-Munzinger, Peter EMMI, GSI Breto Rangel, Guillermo CMS/UC Davis D'Elia, Massimo University of Pisa, INFN Dexheimer, Veronica UFSC - Federal University of Santa Catarina Ding, Heng-Tong Brookhaven National Laboratory Dion, Alan Stony Brook University Dumitru, Adrian RBRC and Baruch College, CUNY Freeman, Walter George Washington University Gavai, Rajiv Tata Institute (TIFR), Mumbai Hanada, Masanori KEK Theory Center Hands, Simon Swansea University Hegde, Prasad Brookhaven National Laboratory Heinke, Craig University of Alberta Horvath, Ivan University of Kentucky Karsch, Frithjof Brookhaven National Laboratory Krieg, Stefan Wuppertal University Lattimer, James Stony Brook University Lee, Frank George Washington University Li, Anyi Institute for Nuclear Theory Liu, Keh-Fei University of Kentucky Lombardo, Maria Paola INFN - LNF Lottini, Stefano Goethe University, Frankfurt am Main Maezawa, Yu Brookhaven National Laboratory Miura, Kohtaroh Laboratori Nazionali di Frascati - INFN Monnai, Akihiko The University of Tokyo Mukherjee, Swagato Brookhaven National Laboratory Myers, Joyce University of Groningen Nakamura, Atsushi RIISE, Hiroshima

  12. On Hokusai's Great wave off Kanagawa: localization, linearity and a rogue wave in sub-Antarctic waters.

    PubMed

    Dudley, J M; Sarano, V; Dias, F

    2013-06-20

    The Hokusai woodcut entitled The great wave off Kanagawa has been interpreted as an unusually large storm wave, likely to be classed as a rogue wave, and possibly generated from nonlinear wave dynamics (J. H. E. Cartwright and H. Nakamura, Notes Rec. R. Soc. 63 , 119-135 (2009)). In this paper, we present a complementary discussion of this hypothesis, discussing in particular how linear and nonlinear mechanisms can both contribute to the emergence of rogue wave events. By making reference to the Great wave 's simultaneous transverse and longitudinal localization, we show that the purely linear mechanism of directional focusing also predicts characteristics consistent with those of the Great wave . In addition, we discuss the properties of a particular rogue wave photographed on the open ocean in sub-Antarctic waters, which shows two-dimensional localization and breaking dynamics remarkably similar to Hokusai's depiction in the woodcut.

  13. On Hokusai's Great wave off Kanagawa: localization, linearity and a rogue wave in sub-Antarctic waters

    PubMed Central

    Dudley, J. M.; Sarano, V.; Dias, F.

    2013-01-01

    The Hokusai woodcut entitled The great wave off Kanagawa has been interpreted as an unusually large storm wave, likely to be classed as a rogue wave, and possibly generated from nonlinear wave dynamics (J. H. E. Cartwright and H. Nakamura, Notes Rec. R. Soc. 63, 119–135 (2009)). In this paper, we present a complementary discussion of this hypothesis, discussing in particular how linear and nonlinear mechanisms can both contribute to the emergence of rogue wave events. By making reference to the Great wave's simultaneous transverse and longitudinal localization, we show that the purely linear mechanism of directional focusing also predicts characteristics consistent with those of the Great wave. In addition, we discuss the properties of a particular rogue wave photographed on the open ocean in sub-Antarctic waters, which shows two-dimensional localization and breaking dynamics remarkably similar to Hokusai's depiction in the woodcut. PMID:24687148

  14. The Spectrum of Torsional Oscillations of the Moon

    NASA Astrophysics Data System (ADS)

    Gudkova, T. V.; Zharkov, V. N.

    2000-11-01

    The diagnostic potentialities of the torsional oscillations for probing the structure of the interiors of the Moon are investigated. Models with no core, a liquid core, and a solid core are considered. The profiles of compressional and shear wave velocities V_P and V_S for the lunar interior estimated by Bills and Ferrari (1977), Goins et al. (1981), and Nakamura (1983) from the Apollo lunar seismic network are used. For all these models, the periods of torsional oscillations for n = 2-100 and four overtones have been calculated. The derivatives of the dimensionless eigenfrequency with respect to the dimensionless shear modulus and density are calculated and tabulated for use. These data can be used to determine corrections to the model density and shear modulus distributions due to their small change. The damping of torsional oscillations is studied. Several trial radial distributions of the dissipative function Q are considered.

  15. The carbon-14 spike in the 8th century was not caused by a cometary impact on Earth

    NASA Astrophysics Data System (ADS)

    Usoskin, Ilya G.; Kovaltsov, Gennady A.

    2015-11-01

    A mysterious increase of radiocarbon 14 C ca. 775 AD in the Earth's atmosphere has been recently found by Miyake et al. (Miyake, F., Nagaya, K., Masuda, K., Nakamura, T. [2012]. Nature, 486, 240). A possible source of this event has been discussed widely, the most likely being an extreme solar energetic particle event. A new exotic hypothesis has been presented recently by Liu et al. (Liu, Y. [2014]. Sci. Rep., 4, 3728) who proposed that the event was caused by a cometary impact on Earth bringing additional 14 C to the atmosphere. Here we calculated a realistic mass and size of such a comet to show that it would have been huge (≈100 km across and 1017-1020 g of mass) and would have produced a disastrous geological/biological impact on Earth. The absence of an evidence for such a dramatic event makes this hypothesis invalid.

  16. A Dancing Black Hole

    NASA Astrophysics Data System (ADS)

    Shoemaker, Deirdre; Smith, Kenneth; Schnetter, Erik; Fiske, David; Laguna, Pablo; Pullin, Jorge

    2002-04-01

    Recently, stationary black holes have been successfully simulated for up to times of approximately 600-1000M, where M is the mass of the black hole. Considering that the expected burst of gravitational radiation from a binary black hole merger would last approximately 200-500M, black hole codes are approaching the point where simulations of mergers may be feasible. We will present two types of simulations of single black holes obtained with a code based on the Baumgarte-Shapiro-Shibata-Nakamura formulation of the Einstein evolution equations. One type of simulations addresses the stability properties of stationary black hole evolutions. The second type of simulations demonstrates the ability of our code to move a black hole through the computational domain. This is accomplished by shifting the stationary black hole solution to a coordinate system in which the location of the black hole is time dependent.

  17. Cognitive functions of intracellular mechanisms for contextual amplification.

    PubMed

    Phillips, William A

    2017-03-01

    Evidence for the hypothesis that input to the apical tufts of neocortical pyramidal cells plays a central role in cognition by amplifying their responses to feedforward input is reviewed. Apical tufts are electrically remote from the soma, and their inputs come from diverse sources including direct feedback from higher cortical regions, indirect feedback via the thalamus, and long-range lateral connections both within and between cortical regions. This suggests that input to tuft dendrites may amplify the cell's response to basal inputs that they receive via layer 4 and which have synapses closer to the soma. ERP data supporting this inference is noted. Intracellular studies of apical amplification (AA) and of disamplification by inhibitory interneurons targeted only at tufts are reviewed. Cognitive processes that have been related to them by computational, electrophysiological, and psychopathological studies are then outlined. These processes include: figure-ground segregation and Gestalt grouping; contextual disambiguation in perception and sentence comprehension; priming; winner-take-all competition; attention and working memory; setting the level of consciousness; cognitive control; and learning. It is argued that theories in cognitive neuroscience should not assume that all neurons function as integrate-and-fire point processors, but should use the capabilities of cells with distinct sites of integration for driving and modulatory inputs. Potentially 'unifying' theories that depend upon these capabilities are reviewed. It is concluded that evolution of the primitives of AA and disamplification in neocortex may have extended cognitive capabilities beyond those built from the long-established primitives of excitation, inhibition, and disinhibition. Copyright © 2015 Elsevier Inc. All rights reserved.

  18. PyMUS: Python-Based Simulation Software for Virtual Experiments on Motor Unit System

    PubMed Central

    Kim, Hojeong; Kim, Minjung

    2018-01-01

    We constructed a physiologically plausible computationally efficient model of a motor unit and developed simulation software that allows for integrative investigations of the input–output processing in the motor unit system. The model motor unit was first built by coupling the motoneuron model and muscle unit model to a simplified axon model. To build the motoneuron model, we used a recently reported two-compartment modeling approach that accurately captures the key cell-type-related electrical properties under both passive conditions (somatic input resistance, membrane time constant, and signal attenuation properties between the soma and the dendrites) and active conditions (rheobase current and afterhyperpolarization duration at the soma and plateau behavior at the dendrites). To construct the muscle unit, we used a recently developed muscle modeling approach that reflects the experimentally identified dependencies of muscle activation dynamics on isometric, isokinetic and dynamic variation in muscle length over a full range of stimulation frequencies. Then, we designed the simulation software based on the object-oriented programing paradigm and developed the software using open-source Python language to be fully operational using graphical user interfaces. Using the developed software, separate simulations could be performed for a single motoneuron, muscle unit and motor unit under a wide range of experimental input protocols, and a hierarchical analysis could be performed from a single channel to the entire system behavior. Our model motor unit and simulation software may represent efficient tools not only for researchers studying the neural control of force production from a cellular perspective but also for instructors and students in motor physiology classroom settings. PMID:29695959

  19. Evidence for strychnine-sensitive glycine receptors in human amygdala.

    PubMed

    Dudeck, O; Lübben, S; Eipper, S; Knörle, R; Kirsch, M; Honegger, J; Zentner, J; Feuerstein, T J

    2003-09-01

    Recent studies suggested the existence of strychnine-sensitive glycine-receptors in mammalian amygdala. In the present study, we investigated the amino acid concentrations as well as immunocytochemical and pharmacological properties of glycine-receptors in fresh human amygdala tissue obtained from epilepsy surgery. High pressure liquid chromatography revealed a considerable amount of glycine and its precursors and glycine-receptors agonists L-serine and taurine in this tissue. Immunohistochemistry using the monoclonal antibody mAb4a, recognizing an epitope common to all alpha-subunit variants of glycine receptors, displayed a specific labeling at the soma and on proximal dendrites of mostly tripolar, large-sized neurons of irregular distribution and arrangement. To elucidate the pharmacological properties of the glycine-receptors found slices of human amygdala were preloaded with [(3)H]-choline and superfused. Glycine induced an overflow of [(3)H]-acetylcholine, which was inhibited by strychnine in a concentration-dependent manner. Furthermore, the glycine-induced release of [(3)H]-acetylcholine was significantly inhibited by furosemide, indicating glycine-induced actions to be attributed to chloride channels. These actions of glycine were not influenced by MK-801, D-CP-Pene or bicuculline. Thus, the effects of glycine did not seem to be mediated through NMDA or GABA receptors. These observations indicate that strychnine-sensitive, chloride-conducting glycine receptors, which elicit the release of [(3)H]-acetylcholine, are present at the soma and on proximal dendrites of neurons in human amygdala. It is hypothesized that glycine may display a regulatory role in amygdaloid functions, probably via cholinergic interneurons.

  20. Homozygous SLC6A17 mutations cause autosomal-recessive intellectual disability with progressive tremor, speech impairment, and behavioral problems.

    PubMed

    Iqbal, Zafar; Willemsen, Marjolein H; Papon, Marie-Amélie; Musante, Luciana; Benevento, Marco; Hu, Hao; Venselaar, Hanka; Wissink-Lindhout, Willemijn M; Vulto-van Silfhout, Anneke T; Vissers, Lisenka E L M; de Brouwer, Arjan P M; Marouillat, Sylviane; Wienker, Thomas F; Ropers, Hans Hilger; Kahrizi, Kimia; Nadif Kasri, Nael; Najmabadi, Hossein; Laumonnier, Frédéric; Kleefstra, Tjitske; van Bokhoven, Hans

    2015-03-05

    We report on Dutch and Iranian families with affected individuals who present with moderate to severe intellectual disability and additional phenotypes including progressive tremor, speech impairment, and behavioral problems in certain individuals. A combination of exome sequencing and homozygosity mapping revealed homozygous mutations c.484G>A (p.Gly162Arg) and c.1898C>G (p.Pro633Arg) in SLC6A17. SLC6A17 is predominantly expressed in the brain, encodes a synaptic vesicular transporter of neutral amino acids and glutamate, and plays an important role in the regulation of glutamatergic synapses. Prediction programs and 3D modeling suggest that the identified mutations are deleterious to protein function. To directly test the functional consequences, we investigated the neuronal subcellular localization of overexpressed wild-type and mutant variants in mouse primary hippocampal neuronal cells. Wild-type protein was present in soma, axons, dendrites, and dendritic spines. p.Pro633Arg altered SLC6A17 was found in soma and proximal dendrites but did not reach spines. p.Gly162Arg altered SLC6A17 showed a normal subcellular distribution but was associated with an abnormal neuronal morphology mainly characterized by the loss of dendritic spines. In summary, our genetic findings implicate homozygous SLC6A17 mutations in autosomal-recessive intellectual disability, and their pathogenic role is strengthened by genetic evidence and in silico and in vitro functional analyses. Copyright © 2015 The American Society of Human Genetics. Published by Elsevier Inc. All rights reserved.

  1. Genetic expansion of chaperonin-containing TCP-1 (CCT/TRiC) complex subunits yields testis-specific isoforms required for spermatogenesis in planarian flatworms.

    PubMed

    Counts, Jenna T; Hester, Tasha M; Rouhana, Labib

    2017-12-01

    Chaperonin-containing Tail-less complex polypeptide 1 (CCT) is a highly conserved, hetero-oligomeric complex that ensures proper folding of actin, tubulin, and regulators of mitosis. Eight subunits (CCT1-8) make up this complex, and every subunit has a homolog expressed in the testes and somatic tissue of the planarian flatworm Schmidtea mediterranea. Gene duplications of four subunits in the genomes of S. mediterranea and other planarian flatworms created paralogs to CCT1, CCT3, CCT4, and CCT8 that are expressed exclusively in the testes. Functional analyses revealed that each CCT subunit expressed in the S. mediterranea soma is essential for homeostatic integrity and survival, whereas sperm elongation defects were observed upon knockdown of each individual testis-specific paralog (Smed-cct1B; Smed-cct3B; Smed-cct4A; and Smed-cct8B), regardless of potential redundancy with paralogs expressed in both testes and soma (Smed-cct1A; Smed-cct3A; Smed-cct4B; and Smed-cct8A). Yet, no detriment was observed in the number of adult somatic stem cells (neoblasts) that maintain differentiated tissue in planarians. Thus, expression of all eight CCT subunits is required to execute the essential functions of the CCT complex. Furthermore, expression of the somatic paralogs in planarian testes is not sufficient to complete spermatogenesis when testis-specific paralogs are knocked down, suggesting that the evolution of chaperonin subunits may drive changes in the development of sperm structure and that correct CCT subunit stoichiometry is crucial for spermiogenesis. © 2017 Wiley Periodicals, Inc.

  2. Cumulative effects of the ApoE genotype and gender on the synaptic proteome and oxidative stress in the mouse brain.

    PubMed

    Shi, Lv; Du, Xin; Zhou, Hong; Tao, Changlu; Liu, Yuntao; Meng, Fantao; Wu, Gao; Xiong, Ying; Xia, Chun; Wang, Yu; Bi, Guoqiang; Zhou, Jiang-Ning

    2014-11-01

    Elderly females, particularly those carrying the apolipoprotein E (ApoE)-ε4 allele, have a higher risk of developing Alzheimer's disease (AD). However, the underlying mechanism for this increased susceptibility remains unclear. In this study, we investigated the effects of the ApoE genotype and gender on the proteome of synaptosomes. We isolated synaptosomes and used label-free quantitative proteomics, to report, for the first time, that the synaptosomal proteomic profiles in the cortex of female human-ApoE4 mice exhibited significantly reduced expression of proteins related to energy metabolism, which was accompanied by increased levels of oxidative stress. In addition, we also first demonstrated that the proteomic response in synaptic termini was more susceptible than that in the soma to the adverse effects induced by genders and genotypes. This suggests that synaptic mitochondria might be 'older' than mitochondria in the soma of neurons; therefore, they might contain increased cumulative damage from oxidative stress. Furthermore, female human-ApoE4 mice had much lower oestrogen levels in the cortex and treatment with oestrogen protected ApoE3 stable transfected C6 neurons from oxidative stress. Overall, this study reveals complex ApoE- and gender-dependent effects on synaptic function and also provides a basis for future studies of candidates based on specific pathways involved in the pathogenesis of AD. The lack of oestrogen-mediated protection regulated by the ApoE genotype led to synaptic mitochondrial dysfunction and increased oxidative stress, which might make older females more susceptible to AD.

  3. Early presymptomatic cholinergic dysfunction in a murine model of amyotrophic lateral sclerosis

    PubMed Central

    Casas, Caty; Herrando-Grabulosa, Mireia; Manzano, Raquel; Mancuso, Renzo; Osta, Rosario; Navarro, Xavier

    2013-01-01

    Sporadic and familiar amyotrophic lateral sclerosis (ALS) cases presented lower cholinergic activity than in healthy individuals in their still preserved spinal motoneurons (MNs) suggesting that cholinergic reduction might occur before MN death. To unravel how and when cholinergic function is compromised, we have analyzed the spatiotemporal expression of choline acetyltransferase (ChAT) from early presymptomatic stages of the SOD1G93A ALS mouse model by confocal immunohistochemistry. The analysis showed an early reduction in ChAT content in soma and presynaptic boutons apposed onto MNs (to 76%) as well as in cholinergic interneurons in the lumbar spinal cord of the 30-day-old SOD1G93A mice. Cholinergic synaptic stripping occurred simultaneously to the presence of abundant surrounding major histocompatibility complex II (MHC-II)-positive microglia and the accumulation of nuclear Tdp-43 and the appearance of mild oxidative stress within MNs. Besides, there was a loss of neuronal MHC-I expression, which is necessary for balanced synaptic stripping after axotomy. These events occurred before the selective raise of markers of denervation such as ATF3. By the same time, alterations in postsynaptic cholinergic-related structures were also revealed with a loss of the presence of sigma-1 receptor, a Ca2+ buffering chaperone in the postsynaptic cisternae. By 2 months of age, ChAT seemed to accumulate in the soma of MNs, and thus efferences toward Renshaw interneurons were drastically diminished. In conclusion, cholinergic dysfunction in the local circuitry of the spinal cord may be one of the earliest events in ALS etiopathogenesis. PMID:23531559

  4. Neuromodulation impact on nonlinear firing behavior of a reduced model motoneuron with the active dendrite

    PubMed Central

    Kim, Hojeong; Heckman, C. J.

    2014-01-01

    Neuromodulatory inputs from brainstem systems modulate the normal function of spinal motoneurons by altering the activation properties of persistent inward currents (PICs) in their dendrites. However, the effect of the PIC on firing outputs also depends on its location in the dendritic tree. To investigate the interaction between PIC neuromodulation and PIC location dependence, we used a two-compartment model that was biologically realistic in that it retains directional and frequency-dependent electrical coupling between the soma and the dendrites, as seen in multi-compartment models based on full anatomical reconstructions of motoneurons. Our two-compartment approach allowed us to systematically vary the coupling parameters between the soma and the dendrite to accurately reproduce the effect of location of the dendritic PIC on the generation of nonlinear (hysteretic) motoneuron firing patterns. Our results show that as a single parameter value for PIC activation was either increased or decreased by 20% from its default value, the solution space of the coupling parameter values for nonlinear firing outputs was drastically reduced by approximately 80%. As a result, the model tended to fire only in a linear mode at the majority of dendritic PIC sites. The same results were obtained when all parameters for the PIC activation simultaneously changed only by approximately ±10%. Our results suggest the democratization effect of neuromodulation: the neuromodulation by the brainstem systems may play a role in switching the motoneurons with PICs at different dendritic locations to a similar mode of firing by reducing the effect of the dendritic location of PICs on the firing behavior. PMID:25309410

  5. Cochlear Pericytes Are Capable of Reversibly Decreasing Capillary Diameter In Vivo After Tumor Necrosis Factor Exposure.

    PubMed

    Bertlich, Mattis; Ihler, Friedrich; Weiss, Bernhard G; Freytag, Saskia; Strupp, Michael; Canis, Martin

    2017-12-01

    The aim of this work was to evaluate the effect of tumor necrosis factor (TNF) and its neutralization with etanercept on the capability of cochlear pericytes to alter capillary diameter in the stria vascularis. Twelve Dunkin-Hartley guinea pigs were randomly assigned to one of three groups. Each group was treated either with placebo and then placebo, TNF and then placebo, or TNF and then etanercept. Cochlear pericytes were visualized using diaminofluorescein-2-diacetate and intravasal blood flow by fluorescein-dextrane. Vessel diameter at sites of pericyte somas and downstream controls were quantified by specialized software. Values were obtained before treatment, after first treatment with tumor necrosis factor or placebo and after second treatment with etanercept or placebo. Overall, 199 pericytes in 12 animals were visualized. After initial treatment with TNF, a significant decrease in vessel diameter at sites of pericyte somas (3.6 ±4.3%, n = 141) compared with placebo and downstream controls was observed. After initial treatment with TNF, the application of etanercept caused a significant increase (3.3 ±5.5%, n = 59) in vessel diameter at the sites of pericyte somata compared with placebo and downstream controls. We have been able to show that cochlear pericytes are capable of reducing capillary diameter after exposition to TNF. Moreover, the reduction in capillary diameter observed after the application of TNF is revertible after neutralization of tumor necrosis factor by the application of etanercept. It seems that contraction of cochlear pericytes contributes to the regulation of cochlear blood flow.

  6. Subcellular Localization and Activity of TRPM4 in Medial Prefrontal Cortex Layer 2/3

    PubMed Central

    Riquelme, Denise; Silva, Ian; Philp, Ashleigh M.; Huidobro-Toro, Juan P.; Cerda, Oscar; Trimmer, James S.; Leiva-Salcedo, Elias

    2018-01-01

    TRPM4 is a Ca2+-activated non-selective cationic channel that conducts monovalent cations. TRPM4 has been proposed to contribute to burst firing and sustained activity in several brain regions, however, the cellular and subcellular pattern of TRPM4 expression in medial prefrontal cortex (mPFC) during postnatal development has not been elucidated. Here, we use multiplex immunofluorescence labeling of brain sections to characterize the postnatal developmental expression of TRPM4 in the mouse mPFC. We also performed electrophysiological recordings to correlate the expression of TRPM4 immunoreactivity with the presence of TRPM4-like currents. We found that TRPM4 is expressed from the first postnatal day, with expression increasing up to postnatal day 35. Additionally, in perforated patch clamp experiments, we found that TRPM4-like currents were active at resting membrane potentials at all postnatal ages studied. Moreover, TRPM4 is expressed in both pyramidal neurons and interneurons. TRPM4 expression is localized in the soma and proximal dendrites, but not in the axon initial segment of pyramidal neurons. This subcellular localization is consistent with a reduction in the basal current only when we locally perfused 9-Phenanthrol in the soma, but not upon perfusion in the medial or distal dendrites. Our results show a specific localization of TRPM4 expression in neurons in the mPFC and that a 9-Phenanthrol sensitive current is active at resting membrane potential, suggesting specific functional roles in mPFC neurons during postnatal development and in adulthood. PMID:29440991

  7. Membrane voltage changes in passive dendritic trees: a tapering equivalent cylinder model.

    PubMed

    Poznański, R R

    1988-01-01

    An exponentially tapering equivalent cylinder model is employed in order to approximate the loss of the dendritic trunk parameter observed from anatomical data on apical and basilar dendrites of CA1 and CA3 hippocampal pyramidal neurons. This model allows dendritic trees with a relative paucity of branching to be treated. In particular, terminal branches are not required to end at the same electrotonic distance. The Laplace transform method is used to obtain analytic expressions for the Green's function corresponding to an instantaneous pulse of current injected at a single point along a tapering equivalent cylinder with sealed ends. The time course of the voltage in response to an arbitrary input is computed using the Green's function in a convolution integral. Examples of current input considered are (1) an infinitesimally brief (Dirac delta function) pulse and (2) a step pulse. It is demonstrated that inputs located on a tapering equivalent cylinder are more effective at the soma than identically placed inputs on a nontapering equivalent cylinder. Asymptotic solutions are derived to enable the voltage response behaviour over both relatively short and long time periods to be analysed. Semilogarithmic plots of these solutions provide a basis for estimating the membrane time constant tau m from experimental transients. Transient voltage decrement from a clamped soma reveals that tapering tends to reduce the error associated with inadequate voltage clamping of the dendritic membrane. A formula is derived which shows that tapering tends to increase the estimate of the electrotonic length parameter L.

  8. PyMUS: Python-Based Simulation Software for Virtual Experiments on Motor Unit System.

    PubMed

    Kim, Hojeong; Kim, Minjung

    2018-01-01

    We constructed a physiologically plausible computationally efficient model of a motor unit and developed simulation software that allows for integrative investigations of the input-output processing in the motor unit system. The model motor unit was first built by coupling the motoneuron model and muscle unit model to a simplified axon model. To build the motoneuron model, we used a recently reported two-compartment modeling approach that accurately captures the key cell-type-related electrical properties under both passive conditions (somatic input resistance, membrane time constant, and signal attenuation properties between the soma and the dendrites) and active conditions (rheobase current and afterhyperpolarization duration at the soma and plateau behavior at the dendrites). To construct the muscle unit, we used a recently developed muscle modeling approach that reflects the experimentally identified dependencies of muscle activation dynamics on isometric, isokinetic and dynamic variation in muscle length over a full range of stimulation frequencies. Then, we designed the simulation software based on the object-oriented programing paradigm and developed the software using open-source Python language to be fully operational using graphical user interfaces. Using the developed software, separate simulations could be performed for a single motoneuron, muscle unit and motor unit under a wide range of experimental input protocols, and a hierarchical analysis could be performed from a single channel to the entire system behavior. Our model motor unit and simulation software may represent efficient tools not only for researchers studying the neural control of force production from a cellular perspective but also for instructors and students in motor physiology classroom settings.

  9. AKAP localizes in a specific subset of TRPV1 and CaV1.2 positive nociceptive rat DRG neurons

    PubMed Central

    Brandao, Katherine E.; Dell’Acqua, Mark L.; Levinson, Simon R.

    2016-01-01

    Modulation of phosphorylation states of ion channels is a critical step in the development of hyperalgesia during inflammation. Modulatory enhancement of channel activity may increase neuronal excitability and affect downstream targets such as gene transcription. The specificity required for such regulation of ion channels quickly occurs via targeting of protein kinases and phosphatases by the scaffolding A-kinase anchoring protein 79/150 (AKAP79/150). AKAP79/150 has been implicated in inflammatory pain by targeting PKA and PKC to the TRPV1 channel in peripheral sensory neurons, thus lowering threshold for activation by multiple inflammatory reagents. However, the expression pattern of AKAP79/150 in peripheral sensory neurons is unknown. In this study we use immunofluorescence microscopy to identify in DRG sections the peripheral neuron subtypes that express the rodent isoform AKAP150, as well as the subcellular distribution of AKAP150 and its potential target ion channels. We found that AKAP150 is predominantly expressed in a subset of small DRG sensory neurons where it is localized at the plasma membrane of the soma, axon initial segment and small fibers. The majority of these neurons is peripherin positive and produces c-fibers, though a small portion produces Aδ-fibers. Furthermore, we demonstrate that AKAP79/150 colocalizes with TRPV1 and CaV1.2 in the soma and axon initial segment. Thus AKAP150 is expressed in small, nociceptive DRG neurons where it is targeted to membrane regions and where it may play a role in the modulation of ion channel phosphorylation states required for hyperalgesia. PMID:21674494

  10. Morphological Characterization of the Action Potential Initiation Segment in GnRH Neuron Dendrites and Axons of Male Mice.

    PubMed

    Herde, Michel K; Herbison, Allan E

    2015-11-01

    GnRH neurons are the final output neurons of the hypothalamic network controlling fertility in mammals. In the present study, we used ankyrin G immunohistochemistry and neurobiotin filling of live GnRH neurons in brain slices from GnRH-green fluorescent protein transgenic male mice to examine in detail the location of action potential initiation in GnRH neurons with somata residing at different locations in the basal forebrain. We found that the vast majority of GnRH neurons are bipolar in morphology, elaborating a thick (primary) and thinner (secondary) dendrite from opposite poles of the soma. In addition, an axon-like process arising predominantly from a proximal dendrite was observed in a subpopulation of GnRH neurons. Ankyrin G immunohistochemistry revealed the presence of a single action potential initiation zone ∼27 μm in length primarily in the secondary dendrite of GnRH neurons and located 30 to 140 μm distant from the cell soma, depending on the type of process and location of the cell body. In addition to dendrites, the GnRH neurons with cell bodies located close to hypothalamic circumventricular organs often elaborated ankyrin G-positive axon-like structures. Almost all GnRH neurons (>90%) had their action potential initiation site in a process that initially, or ultimately after a hairpin loop, was coursing in the direction of the median eminence. These studies indicate that action potentials are initiated in different dendritic and axonal compartments of the GnRH neuron in a manner that is dependent partly on the neuroanatomical location of the cell body.

  11. Spinally projecting neurons of the dorsal column nucleus in a reptile: locus of origin and trajectory of termination.

    PubMed

    Pritz, M B

    1996-01-01

    Interconnections between the dorsal column nucleus and the spinal cord were investigated in a reptile, Caiman crocodilus. After placement of an anterograde tracer into the dorsal column nucleus, descending fibers are seen to leave this nucleus to enter the dorsal funiculus where they course ventrally to terminate in lamina V of the spinal cord as far caudally as C2. Placement of a retrograde tracer into cut fibers of the cervical spinal cord identified the relay cells of the dorsal column nucleus that project to the spinal cord. These neurons were mainly clustered in a caudal and ventral part of this nucleus. The soma of these spinally projecting cells were small and were generally round or oval in shape. A number of these neurons had the long axis of their soma oriented dorsoventrally, with a primary dendrite extending dorsally. Fibers in the dorsal funiculus that originated from the spinal cord enter the caudal part of the dorsal column nucleus and turn ventral. In the dorsal column nucleus, these axons run parallel to the vertically oriented dendrites of these spinally projecting cells before termination in close relation to the cell bodies of these neurons. Quantitative observations (mean +/- standard error) were made on well labeled neurons and included several measurements: area, perimeter, and degree of eccentricity (greatest width/greatest length) in both the transverse as well as the sagittal plane. These spinally projecting neurons in Caiman are located in the dorsal column nucleus in a position similar to that of spinally projecting cells in cats.

  12. Axon topography of layer 6 spiny cells to orientation map in the primary visual cortex of the cat (area 18).

    PubMed

    Karube, Fuyuki; Sári, Katalin; Kisvárday, Zoltán F

    2017-04-01

    To uncover the functional topography of layer 6 neurons, optical imaging was combined with three-dimensional neuronal reconstruction. Apical dendrite morphology of 23 neurons revealed three distinct types. Type Aa possessed a short apical dendrite with many oblique branches, Type Ab was characterized by a short and less branched apical dendrite, whereas Type B had a long apical dendrite with tufts in layer 2. Each type had a similar number of boutons, yet their spatial distribution differed from each other in both radial and horizontal extent. Boutons of Type Aa and Ab were almost restricted to the column of the parent soma with a laminar preference to layer 4 and 5/6, respectively. Only Type B contributed to long horizontal connections (up to 1.5 mm) mostly in deep layers. For all types, bouton distribution on orientation map showed an almost equal occurrence at iso- (52.6 ± 18.8 %) and non-iso-orientation (oblique, 27.7 ± 14.9 % and cross-orientation 19.7 ± 10.9 %) sites. Spatial convergence of axons of nearby layer 6 spiny neurons depended on soma separation of the parent cells, but only weakly on orientation preference, contrary to orientation dependence of converging axons of layer 4 spiny cells. The results show that layer 6 connections have only a weak dependence on orientation preference compared with those of layers 2/3 (Buzás et al., J Comp Neurol 499:861-881, 2006) and 4 (Karube and Kisvárday, Cereb Cortex 21:1443-1458, 2011).

  13. Academic-industrial relations before the blockbuster drugs: lessons from the Harvard Committee on Pharmacotherapy, 1939-1943.

    PubMed

    Podolsky, Scott H; Greene, Jeremy A

    2011-04-01

    Increasing discussion has developed in recent years over the nature of the relationship between academic medicine and the pharmaceutical industry. This article narrates the history of a little-known attempt at Harvard Medical School between 1939 and 1943 to establish an interdisciplinary, academic-industrial Committee on Pharmacotherapy to enhance and rationalize the relationship between the field of academic research in pharmacotherapeutics and the pharmaceutical industry. Using original archival materials, the authors depict the functioning of the committee, which was headed by Soma Weiss and included such members as Fuller Albright, Henry Beecher, and Walter Cannon. The committee would be collectively funded by seven pharmaceutical companies and was to be predicated on collaboration, both across the entire university and between academia and industry. It was expected to transform the bench-to-bedside study and testing of therapeutic compounds, to redefine the teaching of pharmacotherapy, and to create a unified forum through which to discuss the overall academic-industrial relationship and more specific issues such as patents. Unfortunately, the program proved to be short-lived, the victim of such contingent factors as the untimely death of Soma Weiss and America's entry into World War II, as well as such more fundamental factors as the inadequate and temporary nature of the funding stream and unresolved tensions regarding the goals of the committee on the part of both the medical school and its industry supporters. Nevertheless, these early forays into collaborative bench-to-bedside translational research and the rationalization of academic-industrial relations remain instructive today. © by the Association of American Medical Colleges.

  14. Dendrite architecture organized by transcriptional control of the F-actin nucleator Spire.

    PubMed

    Ferreira, Tiago; Ou, Yimiao; Li, Sally; Giniger, Edward; van Meyel, Donald J

    2014-02-01

    The architectures of dendritic trees are crucial for the wiring and function of neuronal circuits because they determine coverage of receptive territories, as well as the nature and strength of sensory or synaptic inputs. Here, we describe a cell-intrinsic pathway sculpting dendritic arborization (da) neurons in Drosophila that requires Longitudinals Lacking (Lola), a BTB/POZ transcription factor, and its control of the F-actin cytoskeleton through Spire (Spir), an actin nucleation protein. Loss of Lola from da neurons reduced the overall length of dendritic arbors, increased the expression of Spir, and produced inappropriate F-actin-rich dendrites at positions too near the cell soma. Selective removal of Lola from only class IV da neurons decreased the evasive responses of larvae to nociception. The increased Spir expression contributed to the abnormal F-actin-rich dendrites and the decreased nocifensive responses because both were suppressed by reduced dose of Spir. Thus, an important role of Lola is to limit expression of Spir to appropriate levels within da neurons. We found Spir to be expressed in dendritic arbors and to be important for their development. Removal of Spir from class IV da neurons reduced F-actin levels and total branch number, shifted the position of greatest branch density away from the cell soma, and compromised nocifensive behavior. We conclude that the Lola-Spir pathway is crucial for the spatial arrangement of branches within dendritic trees and for neural circuit function because it provides balanced control of the F-actin cytoskeleton.

  15. Brain-region–specific alterations of the trajectories of neuronal volume growth throughout the lifespan in autism

    PubMed Central

    2014-01-01

    Several morphometric studies have revealed smaller than normal neurons in the neocortex of autistic subjects. To test the hypothesis that abnormal neuronal growth is a marker of an autism-associated global encephalopathy, neuronal volumes were estimated in 16 brain regions, including various subcortical structures, Ammon’s horn, archicortex, cerebellum, and brainstem in 14 brains from individuals with autism 4 to 60 years of age and 14 age-matched control brains. This stereological study showed a significantly smaller volume of neuronal soma in 14 of 16 regions in the 4- to 8-year-old autistic brains than in the controls. Arbitrary classification revealed a very severe neuronal volume deficit in 14.3% of significantly altered structures, severe in 50%, moderate in 21.4%, and mild in 14.3% structures. This pattern suggests desynchronized neuronal growth in the interacting neuronal networks involved in the autistic phenotype. The comparative study of the autistic and control subject brains revealed that the number of structures with a significant volume deficit decreased from 14 in the 4- to 8-year-old autistic subjects to 4 in the 36- to 60-year-old. Neuronal volumes in 75% of the structures examined in the older adults with autism are comparable to neuronal volume in age-matched controls. This pattern suggests defects of neuronal growth in early childhood and delayed up-regulation of neuronal growth during adolescence and adulthood reducing neuron soma volume deficit in majority of examined regions. However, significant correction of neuron size but limited clinical improvements suggests that delayed correction does not restore functional deficits. PMID:24612906

  16. Subcellular Localization and Activity of TRPM4 in Medial Prefrontal Cortex Layer 2/3.

    PubMed

    Riquelme, Denise; Silva, Ian; Philp, Ashleigh M; Huidobro-Toro, Juan P; Cerda, Oscar; Trimmer, James S; Leiva-Salcedo, Elias

    2018-01-01

    TRPM4 is a Ca 2+ -activated non-selective cationic channel that conducts monovalent cations. TRPM4 has been proposed to contribute to burst firing and sustained activity in several brain regions, however, the cellular and subcellular pattern of TRPM4 expression in medial prefrontal cortex (mPFC) during postnatal development has not been elucidated. Here, we use multiplex immunofluorescence labeling of brain sections to characterize the postnatal developmental expression of TRPM4 in the mouse mPFC. We also performed electrophysiological recordings to correlate the expression of TRPM4 immunoreactivity with the presence of TRPM4-like currents. We found that TRPM4 is expressed from the first postnatal day, with expression increasing up to postnatal day 35. Additionally, in perforated patch clamp experiments, we found that TRPM4-like currents were active at resting membrane potentials at all postnatal ages studied. Moreover, TRPM4 is expressed in both pyramidal neurons and interneurons. TRPM4 expression is localized in the soma and proximal dendrites, but not in the axon initial segment of pyramidal neurons. This subcellular localization is consistent with a reduction in the basal current only when we locally perfused 9-Phenanthrol in the soma, but not upon perfusion in the medial or distal dendrites. Our results show a specific localization of TRPM4 expression in neurons in the mPFC and that a 9-Phenanthrol sensitive current is active at resting membrane potential, suggesting specific functional roles in mPFC neurons during postnatal development and in adulthood.

  17. Automated method for tracing leading and trailing processes of migrating neurons in confocal image sequences

    NASA Astrophysics Data System (ADS)

    Kerekes, Ryan A.; Gleason, Shaun S.; Trivedi, Niraj; Solecki, David J.

    2010-03-01

    Segmentation, tracking, and tracing of neurons in video imagery are important steps in many neuronal migration studies and can be inaccurate and time-consuming when performed manually. In this paper, we present an automated method for tracing the leading and trailing processes of migrating neurons in time-lapse image stacks acquired with a confocal fluorescence microscope. In our approach, we first locate and track the soma of the cell of interest by smoothing each frame and tracking the local maxima through the sequence. We then trace the leading process in each frame by starting at the center of the soma and stepping repeatedly in the most likely direction of the leading process. This direction is found at each step by examining second derivatives of fluorescent intensity along curves of constant radius around the current point. Tracing terminates after a fixed number of steps or when fluorescent intensity drops below a fixed threshold. We evolve the resulting trace to form an improved trace that more closely follows the approximate centerline of the leading process. We apply a similar algorithm to the trailing process of the cell by starting the trace in the opposite direction. We demonstrate our algorithm on two time-lapse confocal video sequences of migrating cerebellar granule neurons (CGNs). We show that the automated traces closely approximate ground truth traces to within 1 or 2 pixels on average. Additionally, we compute line intensity profiles of fluorescence along the automated traces and quantitatively demonstrate their similarity to manually generated profiles in terms of fluorescence peak locations.

  18. Deep brain stimulation during early adolescence prevents microglial alterations in a model of maternal immune activation.

    PubMed

    Hadar, Ravit; Dong, Le; Del-Valle-Anton, Lucia; Guneykaya, Dilansu; Voget, Mareike; Edemann-Callesen, Henriette; Schweibold, Regina; Djodari-Irani, Anais; Goetz, Thomas; Ewing, Samuel; Kettenmann, Helmut; Wolf, Susanne A; Winter, Christine

    2017-07-01

    In recent years schizophrenia has been recognized as a neurodevelopmental disorder likely involving a perinatal insult progressively affecting brain development. The poly I:C maternal immune activation (MIA) rodent model is considered as a neurodevelopmental model of schizophrenia. Using this model we and others demonstrated the association between neuroinflammation in the form of altered microglia and a schizophrenia-like endophenotype. Therapeutic intervention using the anti-inflammatory drug minocycline affected altered microglia activation and was successful in the adult offspring. However, less is known about the effect of preventive therapeutic strategies on microglia properties. Previously we found that deep brain stimulation of the medial prefrontal cortex applied pre-symptomatically to adolescence MIA rats prevented the manifestation of behavioral and structural deficits in adult rats. We here studied the effects of deep brain stimulation during adolescence on microglia properties in adulthood. We found that in the hippocampus and nucleus accumbens, but not in the medial prefrontal cortex, microglial density and soma size were increased in MIA rats. Pro-inflammatory cytokine mRNA was unchanged in all brain areas before and after implantation and stimulation. Stimulation of either the medial prefrontal cortex or the nucleus accumbens normalized microglia density and soma size in main projection areas including the hippocampus and in the area around the electrode implantation. We conclude that in parallel to an alleviation of the symptoms in the rat MIA model, deep brain stimulation has the potential to prevent the neuroinflammatory component in this disease. Copyright © 2016 Elsevier Inc. All rights reserved.

  19. The distribution of excitatory amino acid receptors on acutely dissociated dorsal horn neurons from postnatal rats.

    PubMed

    Arancio, O; Yoshimura, M; Murase, K; MacDermott, A B

    1993-01-01

    Excitatory amino acid receptor distribution was mapped on acutely dissociated neurons from postnatal rat spinal cord dorsal horn. N-methyl D-aspartate, quisqualate and kainate were applied to multiple locations along the somal and dendritic surfaces of voltage-clamped neurons by means of a pressure application system. To partially compensate for the decrement of response amplitude due to current loss between the site of activation on the dendrite and the recording electrode at the soma, a solution containing 0.15 M KCl was applied on the cell bodies and dendrites of some cells to estimate an empirical length constant. In the majority of the cells tested, the dendritic membrane had regions of higher sensitivity to excitatory amino acid agonists than the somatic membrane, with dendritic response amplitudes reaching more than seven times those at the cell body. A comparison of the relative changes in sensitivity between each combination of two of the three excitatory amino acid agonists along the same dendrite showed different patterns of agonist sensitivity along the dendrite in the majority of the cells. These data were obtained from dorsal horn neurons that had developed and formed synaptic connections in vivo. They demonstrate that in contrast to observations made on ventral horn neurons, receptor density for all the excitatory amino acid receptors on dorsal horn neurons, including the N-methyl-D-aspartate receptor, are generally higher on the dendrites than on the soma. Further, these results are similar to those obtained from dorsal horn neurons grown in culture.

  20. Gain-of-function mutations of fem-3, a sex-determination gene in Caenorhabditis elegans

    DOE Office of Scientific and Technical Information (OSTI.GOV)

    Barton, M.K.; Schedl, T.B.; Kimble, J.

    1987-01-01

    The authors have isolated nine gain-of-function (gf) alleles of the sex-determination gene fem-3 as suppressors of feminizing mutations in fem-1 and fem-2. The wild type fem-3 gene is needed for spermatogenesis in XX self-fertilizing hermaphrodites and for male development in both soma and germ line of XO animals. Loss-of-function alleles of fem-3 transform XX and XO animals into females (spermless hermaphrodites). In contrast, fem-3 (gf) alleles masculinize only one tissue, the hermaphrodite germ line. Thus, XX fem-3 (gf) mutant animals have a normal hermaphrodite soma, but the germ line produces a vast excess of sperm and no oocytes. All ninemore » fem-3 (gf) alleles are temperature sensitive. The temperature-sensitive period is from late L4 to early adult, a period just preceding the first signs of oogenesis. The finding of gain-of-function alleles which confer a phenotype opposite to that of loss-of-function alleles supports the idea that fem-3 plays a critical role in germ-line sex determination. Furthermore, the germ-line specificity of the fem-3 (gf) mutant phenotype and the late temperature-sensitive period suggest that, in the wild-type XX hermaphrodite, fem-3 is negatively regulated so that the hermaphrodite stops making sperm and starts making oocytes. Temperature shift experiments also show that, in the germ line, sexual commitment appears to be a continuing process. Spermatogenesis can resume even after oogenesis has begun, and oogenesis can be initiated much later than normal.« less

  1. Combined Exposure to Simulated Microgravity and Acute or Chronic Radiation Reduces Neuronal Network Integrity and Survival

    PubMed Central

    Quintens, Roel; Samari, Nada; de Saint-Georges, Louis; van Oostveldt, Patrick; Baatout, Sarah; Benotmane, Mohammed Abderrafi

    2016-01-01

    During orbital or interplanetary space flights, astronauts are exposed to cosmic radiations and microgravity. However, most earth-based studies on the potential health risks of space conditions have investigated the effects of these two conditions separately. This study aimed at assessing the combined effect of radiation exposure and microgravity on neuronal morphology and survival in vitro. In particular, we investigated the effects of simulated microgravity after acute (X-rays) or during chronic (Californium-252) exposure to ionizing radiation using mouse mature neuron cultures. Acute exposure to low (0.1 Gy) doses of X-rays caused a delay in neurite outgrowth and a reduction in soma size, while only the high dose impaired neuronal survival. Of interest, the strongest effect on neuronal morphology and survival was evident in cells exposed to microgravity and in particular in cells exposed to both microgravity and radiation. Removal of neurons from simulated microgravity for a period of 24 h was not sufficient to recover neurite length, whereas the soma size showed a clear re-adaptation to normal ground conditions. Genome-wide gene expression analysis confirmed a modulation of genes involved in neurite extension, cell survival and synaptic communication, suggesting that these changes might be responsible for the observed morphological effects. In general, the observed synergistic changes in neuronal network integrity and cell survival induced by simulated space conditions might help to better evaluate the astronaut's health risks and underline the importance of investigating the central nervous system and long-term cognition during and after a space flight. PMID:27203085

  2. Do yogis have "Learning Styles"? (A somatic solution).

    PubMed

    Strean, William Ben

    2017-01-01

    Learning styles has captivated a great deal of attention in yoga teacher training. The triad of visual, auditory, and kinesthetic learning styles has been particularly popular; yet as Sharp et al . asserted, such an approach trivializes the complexity of learning and compromises scholarship at all levels of the education community. This paper addresses that although there is great merit in recognizing yoga students' differences and preferences, many uses of learning styles in yoga teacher training are superficial and promote self-handicapping. A somatic perspective (from soma, the body in its wholeness) offers a framework to reconsider the depth of effective learning.

  3. Advanced Targeting Cost Function Design for Evolutionary Optimization of Control of Logistic Equation

    NASA Astrophysics Data System (ADS)

    Senkerik, Roman; Zelinka, Ivan; Davendra, Donald; Oplatkova, Zuzana

    2010-06-01

    This research deals with the optimization of the control of chaos by means of evolutionary algorithms. This work is aimed on an explanation of how to use evolutionary algorithms (EAs) and how to properly define the advanced targeting cost function (CF) securing very fast and precise stabilization of desired state for any initial conditions. As a model of deterministic chaotic system, the one dimensional Logistic equation was used. The evolutionary algorithm Self-Organizing Migrating Algorithm (SOMA) was used in four versions. For each version, repeated simulations were conducted to outline the effectiveness and robustness of used method and targeting CF.

  4. Spectroscopic Studies of Hazardous Fuel Interactions with Soils

    DTIC Science & Technology

    1993-12-01

    J. and Hohl, H. "A Comparison of Electrostatic Models for the Oxide /Solution Interface," Advan. Colloid Inrface =J. la, 265-294 (1980). 2. Soma, Y...DATE AT2 END !AT2 DUN: "AT2" < ATG OND OMD EXAMPLE OF FULL TITLE SPECIFICATION: OMD OND HZ*1*AIR OXID *05061103*D OMD OMD NOTE THAT THE TITLE IS...IRTISK(IW, 512,NSECS*IDFN+ISEC+87, 11) DE ) IEND=-4 DO 201 J=1,4 WRITE(2,1000) IDFN,ISEC WRITE(2,3000) ISTART--IEND+5 IEND-IEND+150 IF (J.EQ.4) IEND=506

  5. Effects of prenatal binge-like ethanol exposure and maternal stress on postnatal morphological development of hippocampal neurons in rats.

    PubMed

    Jakubowska-Dogru, Ewa; Elibol, Birsen; Dursun, Ilknur; Yürüker, Sinan

    2017-10-01

    Alcohol is one of the most commonly used drugs of abuse negatively affecting human health and it is known as a potent teratogen responsible for fetal alcohol syndrome (FAS), which is characterized by cognitive deficits especially pronounced in juveniles but ameliorating in adults. Searching for the potential morphological correlates of these effects, in this study, we compared the course of developmental changes in the morphology of principal hippocampal neurons in fetal-alcohol (A group), intubated control (IC group), and intact control male rats (C group) over a protracted period of the first two postnatal months. Ethanol was administered to the pregnant Wistar dams intragastrically, throughout gestation days (GD) 7-20, at a total dose of 6g/kg/day resulting in the mean blood alcohol concentration (BAC) of 246.6±40.9mg/dl. Ten morphometric parameters of Golgi-stained hippocampal neurons (pyramidal and granule) from CA1, CA3, and DG areas were examined at critical postnatal days (PD): at birth (PD1), at the end of the brain growth spurt period (PD10), in juveniles (PD30), and in young adults (PD60). During postnatal development, the temporal pattern of morphometric changes was shown to be region-dependent with most significant alterations observed between PD1-30 in the CA region and between PD10-30 in the DG region. It was also parameter-dependent with the soma size (except for CA3 pyramids), number of primary dendrites, dendrite diameter, dendritic tortuosity and the branch angle demonstrating little changes, while the total dendritic field area, dendritic length, number of dendritic bifurcations, and spine density being highly increased in all hippocampal regions during the first postnatal month. Moderate ethanol intoxication and the maternal intubation stress during gestation, showed similar, transient effects on the neuron development manifested as a smaller soma size in granule cells, reduced dendritic parameters and lower spine density in pyramidal neurons

  6. [Oguchi disease or stationary congenital night blindness: a case report].

    PubMed

    Boissonnot, M; Robert, M F; Gilbert-Dussardier, B; Dighiero, P

    2007-01-01

    Oguchi disease, originally described in Japanese people, is a rare form of stationary night blindness in patients with normal acuity. We report the case of an 8-year-old girl who presented with an abnormal terrified behavior in the dark. Thorough questioning revealed hemeralopia. Her clinical examination (visual acuity, Goldmann visual field, and color vision) were normal. The fundus examination showed golden-brown color, grayish, almost greenish yellow discoloration in the peripheral area with no osteoclast. This abnormality disappeared after prolonged dark adaptation. The electroretinogram showed a reduced b wave amplitude under scotopic conditions. Her parents were cousins. This diagnosis should be suggested when hemeralopia is associated with typical fundus aspect resolving after dark adaptation (so called Mizuo-Nakamura phenomenon). The long-term prognosis in these patients is good in the absence of clinical progression. This is a genetic autosomal recessive disease caused by mutations in the gene coding for arrestin located in 2q37.1.

  7. Laser control of reactions of photoswitching functional molecules.

    PubMed

    Tamura, Hiroyuki; Nanbu, Shinkoh; Ishida, Toshimasa; Nakamura, Hiroki

    2006-07-21

    Laser control schemes of reactions of photoswitching functional molecules are proposed based on the quantum mechanical wave-packet dynamics and the design of laser parameters. The appropriately designed quadratically chirped laser pulses can achieve nearly complete transitions of wave packet among electronic states. The laser parameters can be optimized by using the Zhu-Nakamura theory of nonadiabatic transition. This method is effective not only for the initial photoexcitation process but also for the pump and dump scheme in the middle of the overall photoswitching process. The effects of momentum of the wave packet crossing a conical intersection on the branching ratio of products have also been clarified. These control schemes mentioned above are successfully applied to the cyclohexadiene/hexatriene photoisomerization (ring-opening) process which is the reaction center of practical photoswitching molecules such as diarylethenes. The overall efficiency of the ring opening can be appreciably increased by using the appropriately designed laser pulses compared to that of the natural photoisomerization without any control schemes.

  8. Quantum Cryptography Based on the Deutsch-Jozsa Algorithm

    NASA Astrophysics Data System (ADS)

    Nagata, Koji; Nakamura, Tadao; Farouk, Ahmed

    2017-09-01

    Recently, secure quantum key distribution based on Deutsch's algorithm using the Bell state is reported (Nagata and Nakamura, Int. J. Theor. Phys. doi: 10.1007/s10773-017-3352-4, 2017). Our aim is of extending the result to a multipartite system. In this paper, we propose a highly speedy key distribution protocol. We present sequre quantum key distribution based on a special Deutsch-Jozsa algorithm using Greenberger-Horne-Zeilinger states. Bob has promised to use a function f which is of one of two kinds; either the value of f( x) is constant for all values of x, or else the value of f( x) is balanced, that is, equal to 1 for exactly half of the possible x, and 0 for the other half. Here, we introduce an additional condition to the function when it is balanced. Our quantum key distribution overcomes a classical counterpart by a factor O(2 N ).

  9. Local finite-amplitude wave activity as an objective diagnostic of midlatitude extreme weather

    DOE Office of Scientific and Technical Information (OSTI.GOV)

    Chen, Gang; Lu, Jian; Burrows, Alex D.

    Midlatitude extreme weather events are responsible for a large part of climate related damage, yet our understanding of these extreme events is limited, partly due to the lack of a theoretical basis for midlatitude extreme weather. In this letter, the local finite-amplitude wave activity (LWA) of Huang and Nakamura [2015] is introduced as a diagnostic of the 500-hPa geopotential height (Z500) to characterizing midlatitude weather events. It is found that the LWA climatology and its variability associated with the Arctic Oscillation (AO) agree broadly with the previously reported blocking frequency in literature. There is a strong seasonal and spatial dependencemore » in the trend13 s of LWA in recent decades. While there is no observational evidence for a hemispheric-scale increase in wave amplitude, robust trends in wave activity can be identified at the regional scales, with important implications for regional climate change.« less

  10. Lead-free piezoelectrics based on potassium-sodium niobate with giant d(33).

    PubMed

    Zhang, Binyu; Wu, Jiagang; Cheng, Xiaojing; Wang, Xiaopeng; Xiao, Dingquan; Zhu, Jianguo; Wang, Xiangjian; Lou, Xiaojie

    2013-08-28

    High-performance lead-free piezoelectrics (d33 > 400 pC/N) based on 0.96(K0.5Na0.5)0.95Li0.05Nb1-xSbxO3-0.04BaZrO3 with the rhombohedral-tetragonal (R-T) phase boundary have been designed and prepared. The R-T phase boundary lies the composition range of 0.04 ≤ x ≤ 0.07, and the dielectric and piezoelectric properties of the ceramics with the compositions near the phase boundary are significantly enhanced. In addition, the ceramic with x = 0.07 has a giant d33 of ~425 pC/N, which is comparable to that (~416 pC/N) of textured KNN-based ceramics (Saito, Y.; Takao, H.; Tani, T.; Nonoyama, T.; Takatori, K.; Homma, T.; Nagaya, T.; Nakamura, M. Nature 2004, 432, 84). The underlying physical mechanisms for enhanced piezoelectric properties are addressed. We believe that the material system is the most promising lead-free piezoelectric candidates for the practical applications.

  11. Non-adiabatic dynamics of isolated green fluorescent protein chromophore anion

    DOE Office of Scientific and Technical Information (OSTI.GOV)

    Zhao, Li, E-mail: zhaoli282@dicp.ac.cn, E-mail: pwzhou@dicp.ac.cn, E-mail: libinsnet@dicp.ac.cn, E-mail: aihuagao@dicp.ac.cn; Gao, Ai-Hua, E-mail: zhaoli282@dicp.ac.cn, E-mail: pwzhou@dicp.ac.cn, E-mail: libinsnet@dicp.ac.cn, E-mail: aihuagao@dicp.ac.cn; University of the Chinese Academy of Sciences, Beijing 100049

    2014-12-21

    On-the-fly ab initio molecular dynamics calculations have been performed to investigate the relaxation mechanism of green fluorescent protein chromophore anion under vacuum. The CASSCF surface hopping simulation method based on Zhu-Nakamura theory is applied to present the real-time conformational changes of the target molecule. The static calculations and dynamics simulation results suggest that not only the twisting motion around bridging bonds between imidazolinone and phenoxy groups but the strength mode of C=O and pyramidalization character of bridging atom are major factors on the ultrafast fluorescence quenching process of the isolated chromophore anion. The abovementioned factors bring the molecule to themore » vicinity of conical intersections on its potential energy surface and to finish the internal conversion process. A Hula-like twisting pattern is displayed during the relaxation process and the entire decay process disfavors a photoswitching pattern which corresponds to cis-trans photoisomerization.« less

  12. Boolean approach to dichotomic quantum measurement theories

    NASA Astrophysics Data System (ADS)

    Nagata, K.; Nakamura, T.; Batle, J.; Abdalla, S.; Farouk, A.

    2017-02-01

    Recently, a new measurement theory based on truth values was proposed by Nagata and Nakamura [Int. J. Theor. Phys. 55, 3616 (2016)], that is, a theory where the results of measurements are either 0 or 1. The standard measurement theory accepts a hidden variable model for a single Pauli observable. Hence, we can introduce a classical probability space for the measurement theory in this particular case. Additionally, we discuss in the present contribution the fact that projective measurement theories (the results of which are either +1 or -1) imply the Bell, Kochen, and Specker (BKS) paradox for a single Pauli observable. To justify our assertion, we present the BKS theorem in almost all the two-dimensional states by using a projective measurement theory. As an example, we present the BKS theorem in two-dimensions with white noise. Our discussion provides new insight into the quantum measurement problem by using this measurement theory based on the truth values.

  13. Habitat Suitability Index Models: Juvenile Atlantic Croaker

    USGS Publications Warehouse

    Diaz, Robert J.; Onuf, Christopher P.

    1982-01-01

    INTRODUCTION The Atlantic croaker is an important commercial and recreational species. In the 1940's, the foodfish catch of Atlantic croakers was concentrated in Chesapeake Bay; in the 1950's and early 1970's, the catch was concentrated in the Gulf of Mexico; and in the late 1970's, the catch was concentrated in the South Atlantic States (Wilk 1981). Industrial and recreational catches of Atlantic croakers have been concentrated in the Gulf of Mexico, where the Atlantic croaker is the most important species of bottomfish for industrial uses (Knudsen and Herke 1978), and has ranked first, second, or third in number caught by recreational anglers, depending on survey year (Nakamura 1981). Today, Virginia or Delaware is considered to be the northern extent of the species. During climatically warmer periods, such as the 1930's and 1940's, the croaker extended its range north at least to New York, where it was commercially fished. The southern extent of its range is Argentina.

  14. Nonadiabatic ab initio molecular dynamics with PME-ONIOM scheme of photoisomerization reaction between 1,3-cyclohexadiene and 1,3,5-cis-hexatriene in solution phase

    NASA Astrophysics Data System (ADS)

    Ohta, Ayumi; Kobayashi, Osamu; Danielache, Sebastian O.; Nanbu, Shinkoh

    2017-03-01

    The ultra-fast photoisomerization reactions between 1,3-cyclohexadiene (CHD) and 1,3,5-cis-hexatriene (HT) in both hexane and ethanol solvents were revealed by nonadiabatic ab initio molecular dynamics (AI-MD) with a particle-mesh Ewald summation method and our Own N-layered Integrated molecular Orbital and molecular Mechanics model (PME-ONIOM) scheme. Zhu-Nakamura version trajectory surface hopping method (ZN-TSH) was employed to treat the ultra-fast nonadiabatic decaying process. The results for hexane and ethanol simulations reasonably agree with experimental data. The high nonpolar-nonpolar affinity between CHD and the solvent was observed in hexane solvent, which definitely affected the excited state lifetimes, the product branching ratio of CHD:HT, and solute (CHD) dynamics. In ethanol solvent, however, the CHD solute was isomerized in the solvent cage caused by the first solvation shell. The photochemical dynamics in ethanol solvent results in the similar property to the process appeared in vacuo (isolated CHD dynamics).

  15. Creatine pretreatment protects cortical axons from energy depletion in vitro

    PubMed Central

    Shen, Hua; Goldberg, Mark P.

    2012-01-01

    Creatine is a natural nitrogenous guanidino compound involved in bioenergy metabolism. Although creatine has been shown to protect neurons of the central nervous system (CNS) from experimental hypoxia/ischemia, it remains unclear if creatine may also protect CNS axons, and if the potential axonal protection depends on glial cells. To evaluate the direct impact of creatine on CNS axons, cortical axons were cultured in a separate compartment from their somas and proximal neurites using a modified two-compartment culture device. Axons in the axon compartment were subjected to acute energy depletion, an in vitro model of white matter ischemia, by exposure to 6 mM sodium azide for 30 min in the absence of glucose and pyruvate. Energy depletion reduced axonal ATP by 65%, depolarized axonal resting potential, and damaged 75% of axons. Application of creatine (10 mM) to both compartments of the culture at 24 h prior to energy depletion significantly reduced axonal damage by 50%. In line with the role of creatine in the bioenergy metabolism, this application also alleviated the axonal ATP loss and depolarization. Inhibition of axonal depolarization by blocking sodium influx with tetrodotoxin also effectively reduced the axonal damage caused by energy depletion. Further study revealed that the creatine effect was independent of glial cells, as axonal protection was sustained even when creatine was applied only to the axon compartment (free from somas and glial cells) for as little as 2 h. In contrast, application of creatine after energy depletion did not protect axons. The data provide the first evidence that creatine pretreatment may directly protect CNS axons from energy deficiency. PMID:22521466

  16. Social dominance explains within-ejaculate variation in sperm design in a passerine bird.

    PubMed

    Rojas Mora, Alfonso; Meniri, Magali; Ciprietti, Sabrina; Helfenstein, Fabrice

    2017-03-04

    Comparative studies suggest that sperm competition exerts stabilizing selection towards an optimal sperm design - e.g., the relative size and covariation of different sperm sections or a quantitative measure of sperm shape - that maximizes male fertility, which results in reduced levels of within-male variation in sperm morphology. Yet, these studies also reveal substantial amounts of unexplained within-ejaculate variance, and the factors presiding to the maintenance of such within-male variation in sperm design at the population level still remain to be identified. Sperm competition models predict that males should progressively invest more resources in their germline as their mating costs increase, i.e., the soma/germline allocation trade-off hypothesis. When access to fertile females is determined by social dominance, the soma/germline allocation trade-off hypothesis predicts that dominant males should invest less in the control of spermatogenesis. Hence, dominance should positively correlate with within-male variance in sperm design. In support of this hypothesis, we found that dominant house sparrow males produce ejaculates with higher levels of within-ejaculate variation in sperm design compared to subordinate males. However, after experimentally manipulating male social status, this pattern was not maintained. Our results suggest that males might control variation in sperm design according to their social status to some extent. Yet, it seems that such within-ejaculate variation in sperm design cannot be rapidly adjusted to a new status. While variation in sperm design could result from various non-exclusive sources, we discuss how strategic allocation of resources to the somatic vs. the germline functions could be an important process shaping the relationship between within-male variation in sperm design and social status.

  17. Spontaneous release from mossy fiber terminals inhibits Ni2+-sensitive T-type Ca2+ channels of CA3 pyramidal neurons in the rat organotypic hippocampal slice.

    PubMed

    Reid, Christopher A; Xu, Shenghong; Williams, David A

    2008-01-01

    Mossy fibers (axons arising from dentate granule cells) form large synaptic contacts exclusively onto the proximal apical dendrites of CA3 pyramidal neurons. They can generate large synaptic currents that occur in close proximity to the soma. These properties mean that active conductance in the proximal apical dendrite could have a disproportionate influence on CA3 pyramidal neuron excitability. Ni(2+)-sensitive T-type Ca(2+) channels are important modulators of dendritic excitability. Here, we use an optical approach to determine the contribution of Ni(2+) (100 microM)-sensitive Ca(2+) channels to action potential (AP) elicited Ca(2+) flux in the soma, proximal apical and distal apical dendrites. At resting membrane potentials Ni(2+)-sensitive Ca(2+) channels do not contribute to the Ca(2+) signal in the proximal apical dendrite, but do contribute in the other cell regions. Spontaneous release from mossy fiber terminals acting on 6-cyano-7-nitroquinoxaline-2,3-dione (CNQX)-sensitive postsynaptic channels underlies a tonic inhibition of Ni(2+)-sensitive channels. Chelating Zn(2+) with CaEDTA blocks CNQX-sensitive changes in Ca(2+) flux implicating a mechanistic role of this ion in T-type Ca(2+) channel block. To test if this inhibition influenced excitability, progressively larger depolarizing pulses were delivered to CA3 pyramidal neurons. CNQX significantly reduced the size of the depolarizing step required to generate APs and increased the absolute number of APs per depolarizing step. This change in AP firing was completely reversed by the addition of Ni(2+). This mechanism may reduce the impact of T-type Ca(2+) channels in a region where large synaptic events are common.

  18. Chronic depolarization enhances the trophic effects of BDNF in rescuing auditory neurons following a sensorineural hearing loss

    PubMed Central

    Shepherd, Robert K.; Coco, Anne; Epp, Stephanie B.; Crook, Jeremy M.

    2007-01-01

    The development and maintenance of spiral ganglion neurons (SGNs) appears to be supported by both neural activity and neurotrophins. Removal of this support leads to their gradual degeneration. Here, we examine whether the exogenous delivery of the neurotrophin brain-derived neurotrophic factor (BDNF) in concert with electrical stimulation (ES) provides a greater protective effect than delivery of BDNF alone in vivo. The left cochlea of profoundly deafened guinea pigs was implanted with an electrode array and drug delivery system. BDNF or artificial perilymph (AP) was delivered continuously for 28 days. ES induced neural activity in two cohorts (BDNF/ES and AP/ES) while control animals received BDNF or AP without ES (BDNF/- and AP/-). The right cochleae of each animal served as deafened untreated controls. Electrically-evoked auditory brainstem responses (EABRs) were recorded immediately following surgery and at completion of the drug delivery period. AP/ES and AP/- cohorts showed an increase in EABR threshold over the implantation period while both BDNF cohorts exhibited a reduction in threshold (P < 0.001, t-test). Changes in neural sensitivity were complemented by significant differences in both SGN survival and soma area. BDNF cohorts demonstrated a significant trophic or survival advantage and larger soma area compared with AP-treated and deafened control cochleae; this advantage was greatest in the base of the cochlea. Importantly, ES significantly enhanced the survival effects of BDNF throughout the majority of the cochlea (P < 0.05, Bonferroni's test), while there was no evidence of trophic support provided by ES alone. Co-treatment of SGNs with BDNF and ES provide a substantial functional and trophic advantage; this treatment may have important implications for neural prostheses. PMID:15844207

  19. BDNF promotes the growth of human neurons through crosstalk with the Wnt/β-catenin signaling pathway via GSK-3β.

    PubMed

    Yang, Jin-Wei; Ru, Jin; Ma, Wei; Gao, Yan; Liang, Zhang; Liu, Jia; Guo, Jian-Hui; Li, Li-Yan

    2015-12-01

    Brain-derived neurotrophic factor (BDNF) plays an important role in neuronal growth; however, the downstream regulatory mechanisms remain unclear. In this study, we investigated whether BDNF exerts its neurotrophic effects through the Wnt/β-catenin signaling pathway in human embryonic spinal cord neurons in vitro. We found that neuronal growth (soma size and average neurite length) was increased by transfection with a BDNF overexpression plasmid. Western blotting and real-time quantitative PCR showed that expression of the BDNF pathway components TrkB, PI3K, Akt and PLC-γ was increased by BDNF overexpression. Furthermore, the Wnt signaling factors Wnt, Frizzled and Dsh and the downstream target β-catenin were upregulated, whereas GSK-3β was downregulated. In contrast, when BDNF signaling was downregulated with BDNF siRNA, the growth of neurons was decreased. Furthermore, BDNF signaling factors, Wnt pathway components and β-catenin were all downregulated, whereas GSK-3β was upregulated. This suggests that BDNF affects the growth of neurons in vitro through crosstalk with Wnt signaling, and that GSK-3β may be a critical factor linking these two pathways. To evaluate this possibility, we treated neurons with 6-bromoindirubin-3'-oxime (BIO), a small molecule GSK-3β inhibitor. BIO reduced the effects of BDNF upregulation/downregulation on soma size and average neurite length, and suppressed the impact of BDNF modulation on the Wnt signaling pathway. Taken together, our findings suggest that BDNF promotes the growth of neurons in vitro through crosstalk with the Wnt/β-catenin signaling pathway, and that this interaction may be mediated by GSK-3β. Copyright © 2015 Elsevier Ltd. All rights reserved.

  20. Distribution of L-type calcium channels in rat thalamic neurones.

    PubMed

    Budde, T; Munsch, T; Pape, H C

    1998-02-01

    One major pathway for calcium entry into neurones is through voltage-activated calcium channels. The distribution of calcium channels over the membrane surface is important for their contribution to neuronal function. Electrophysiological recordings from thalamic cells in situ and after acute isolation demonstrated the presence of high-voltage activated calcium currents. The use of specific L-type calcium channel agonists and antagonists of the dihydropyridine type revealed an about 40% contribution of L-type channels to the total high-voltage-activated calcium current. In order to localize L-type calcium channels in thalamic neurones, fluorescent dihydropyridines were used. They were combined with the fluorescent dye RH414, which allowed the use of a ratio technique and thereby the determination of channel density. The distribution of L-type channels was analysed in the three main thalamic cell types: thalamocortical relay cells, local interneurones and reticular thalamic neurones. While channel density was highest in the soma and decreased significantly in the dendritic region, channels appeared to be clustered differentially in the three types of cells. In thalamocortical cells, L-type channels were clustered in high density around the base of dendrites, while they were more evenly distributed on the soma of interneurones. Reticular thalamic neurones exhibited high density of L-type channels in more central somatic regions. The differential localization of L-type calcium channels found in this study implies their predominate involvement in the regulation of somatic and proximal dendritic calcium-dependent processes, which may be of importance for specific thalamic functions, such as those mediating the transition from rhythmic burst activity during sleep to single spike activity during wakefulness or regulating the relay of visual information.

  1. Autosomal Genes of Autosomal/X-Linked Duplicated Gene Pairs and Germ-Line Proliferation in Caenorhabditis elegans

    PubMed Central

    Maciejowski, John; Ahn, James Hyungsoo; Cipriani, Patricia Giselle; Killian, Darrell J.; Chaudhary, Aisha L.; Lee, Ji Inn; Voutev, Roumen; Johnsen, Robert C.; Baillie, David L.; Gunsalus, Kristin C.; Fitch, David H. A.; Hubbard, E. Jane Albert

    2005-01-01

    We report molecular genetic studies of three genes involved in early germ-line proliferation in Caenorhabditis elegans that lend unexpected insight into a germ-line/soma functional separation of autosomal/X-linked duplicated gene pairs. In a genetic screen for germ-line proliferation-defective mutants, we identified mutations in rpl-11.1 (L11 protein of the large ribosomal subunit), pab-1 [a poly(A)-binding protein], and glp-3/eft-3 (an elongation factor 1-α homolog). All three are members of autosome/X gene pairs. Consistent with a germ-line-restricted function of rpl-11.1 and pab-1, mutations in these genes extend life span and cause gigantism. We further examined the RNAi phenotypes of the three sets of rpl genes (rpl-11, rpl-24, and rpl-25) and found that for the two rpl genes with autosomal/X-linked pairs (rpl-11 and rpl-25), zygotic germ-line function is carried by the autosomal copy. Available RNAi results for highly conserved autosomal/X-linked gene pairs suggest that other duplicated genes may follow a similar trend. The three rpl and the pab-1/2 duplications predate the divergence between C. elegans and C. briggsae, while the eft-3/4 duplication appears to have occurred in the lineage to C. elegans after it diverged from C. briggsae. The duplicated C. briggsae orthologs of the three C. elegans autosomal/X-linked gene pairs also display functional differences between paralogs. We present hypotheses for evolutionary mechanisms that may underlie germ-line/soma subfunctionalization of duplicated genes, taking into account the role of X chromosome silencing in the germ line and analogous mammalian phenomena. PMID:15687263

  2. Theta frequency background tunes transmission but not summation of spiking responses.

    PubMed

    Parameshwaran, Dhanya; Bhalla, Upinder S

    2013-01-01

    Hippocampal neurons are known to fire as a function of frequency and phase of spontaneous network rhythms, associated with the animal's behaviour. This dependence is believed to give rise to precise rate and temporal codes. However, it is not well understood how these periodic membrane potential fluctuations affect the integration of synaptic inputs. Here we used sinusoidal current injection to the soma of CA1 pyramidal neurons in the rat brain slice to simulate background oscillations in the physiologically relevant theta and gamma frequency range. We used a detailed compartmental model to show that somatic current injection gave comparable results to more physiological synaptically driven theta rhythms incorporating excitatory input in the dendrites, and inhibitory input near the soma. We systematically varied the phase of synaptic inputs with respect to this background, and recorded changes in response and summation properties of CA1 neurons using whole-cell patch recordings. The response of the cell was dependent on both the phase of synaptic inputs and frequency of the background input. The probability of the cell spiking for a given synaptic input was up to 40% greater during the depolarized phases between 30-135 degrees of theta frequency current injection. Summation gain on the other hand, was not affected either by the background frequency or the phasic afferent inputs. This flat summation gain, coupled with the enhanced spiking probability during depolarized phases of the theta cycle, resulted in enhanced transmission of summed inputs during the same phase window of 30-135 degrees. Overall, our study suggests that although oscillations provide windows of opportunity to selectively boost transmission and EPSP size, summation of synaptic inputs remains unaffected during membrane oscillations.

  3. Expression of Glial Cell Line-Derived Neurotrophic Factor (GDNF) and the GDNF Family Receptor Alpha Subunit 1 in the Paravaginal Ganglia of Nulliparous and Primiparous Rabbits.

    PubMed

    García-Villamar, Verónica; Hernández-Aragón, Laura G; Chávez-Ríos, Jesús R; Ortega, Arturo; Martínez-Gómez, Margarita; Castelán, Francisco

    2018-01-01

    To evaluate the expression of glial cell line-derived neurotrophic factor (GDNF) and its receptor, GDNF family receptor alpha subunit 1 (GFRα-1) in the pelvic (middle third) vagina and, particularly, in the paravaginal ganglia of nulliparous and primiparous rabbits. Chinchilla-breed female rabbits were used. Primiparas were killed on postpartum day 3 and nulliparas upon reaching a similar age. The vaginal tracts were processed for histological analyses or frozen for Western blot assays. We measured the ganglionic area, the Abercrombie-corrected number of paravaginal neurons, the cross-sectional area of the neuronal somata, and the number of satellite glial cells (SGCs) per neuron. The relative expression of both GDNF and GFRα-1 were assessed by Western blotting, and the immunostaining was semiquantitated. Unpaired two-tailed Student t -test or Wilcoxon test was used to identify statistically significant differences (P≤0.05) between the groups. Our findings demonstrated that the ganglionic area, neuronal soma size, Abercrombie-corrected number of neurons, and number of SGCs per neuron were similar in nulliparas and primiparas. The relative expression of both GDNF and GFRα-1 was similar. Immunostaining for both GDNF and GFRα-1 was observed in several vaginal layers, and no differences were detected regarding GDNF and GFRα-1 immunostaining between the 2 groups. In the paravaginal ganglia, the expression of GDNF was increased in neurons, while that of GFRα-1 was augmented in the SGCs of primiparous rabbits. The present findings suggest an ongoing regenerative process related to the recovery of neuronal soma size in the paravaginal ganglia, in which GDNF and GFRα-1 could be involved in cross-talk between neurons and SGCs.

  4. Axodendritic sorting and pathological missorting of Tau are isoform-specific and determined by axon initial segment architecture.

    PubMed

    Zempel, Hans; Dennissen, Frank J A; Kumar, Yatender; Luedtke, Julia; Biernat, Jacek; Mandelkow, Eva-Maria; Mandelkow, Eckhard

    2017-07-21

    Subcellular mislocalization of the microtubule-associated protein Tau is a hallmark of Alzheimer disease (AD) and other tauopathies. Six Tau isoforms, differentiated by the presence or absence of a second repeat or of N-terminal inserts, exist in the human CNS, but their physiological and pathological differences have long remained elusive. Here, we investigated the properties and distributions of human and rodent Tau isoforms in primary forebrain rodent neurons. We found that the Tau diffusion barrier (TDB), located within the axon initial segment (AIS), controls retrograde (axon-to-soma) and anterograde (soma-to-axon) traffic of Tau. Tau isoforms without the N-terminal inserts were sorted efficiently into the axon. However, the longest isoform (2N4R-Tau) was partially retained in cell bodies and dendrites, where it accelerated spine and dendrite growth. The TDB (located within the AIS) was impaired when AIS components (ankyrin G, EB1) were knocked down or when glycogen synthase kinase-3β (GSK3β; an AD-associated kinase tethered to the AIS) was overexpressed. Using superresolution nanoscopy and live-cell imaging, we observed that microtubules within the AIS appeared highly dynamic, a feature essential for the TDB. Pathomechanistically, amyloid-β insult caused cofilin activation and F-actin remodeling and decreased microtubule dynamics in the AIS. Concomitantly with these amyloid-β-induced disruptions, the AIS/TDB sorting function failed, causing AD-like Tau missorting. In summary, we provide evidence that the human and rodent Tau isoforms differ in axodendritic sorting and amyloid-β-induced missorting and that the axodendritic distribution of Tau depends on AIS integrity. © 2017 by The American Society for Biochemistry and Molecular Biology, Inc.

  5. Metabotropic glutamate receptors activate dendritic calcium waves and TRPM channels which drive rhythmic respiratory patterns in mice

    PubMed Central

    Mironov, S L

    2008-01-01

    Respiration in vertebrates is generated by a compact network which is located in the lower brainstem but cellular mechanisms which underlie persistent oscillatory activity of the respiratory network are yet unknown. Using two-photon imaging and patch-clamp recordings in functional brainstem preparations of mice containing pre-Bötzinger complex (preBötC), we examined the actions of metabotropic glutamate receptors (mGluR1/5) on the respiratory patterns. The agonist DHPG potentiated and antagonist LY367385 depressed respiration-related activities. In the inspiratory neurons, we observed rhythmic activation of non-selective channels which had a conductance of 24 pS. Their activity was enhanced with membrane depolarization and after elevation of calcium from the cytoplasmic side of the membrane. They were activated by a non-hydrolysable PIP2 analogue and blocked by flufenamate, ATP4− and Gd3+. All these properties correspond well to those of TRPM4 channels. Calcium imaging of functional slices revealed rhythmic transients in small clusters of neurons present in a network. Calcium transients in the soma were preceded by the waves in dendrites which were dependent on mGluR activation. Initiation and propagation of waves required calcium influx and calcium release from internal stores. Calcium waves activated TPRM4-like channels in the soma and promoted generation of inspiratory bursts. Simulations of activity of neurons communicated via dendritic calcium waves showed emerging activity within neuronal clusters and its synchronization between the clusters. The experimental and theoretical data provide a subcellular basis for a recently proposed group-pacemaker hypothesis and describe a novel mechanism of rhythm generation in neuronal networks. PMID:18308826

  6. Chronic administration of resveratrol prevents morphological changes in prefrontal cortex and hippocampus of aged rats.

    PubMed

    Monserrat Hernández-Hernández, Elizabeth; Serrano-García, Carolina; Antonio Vázquez-Roque, Rubén; Díaz, Alfonso; Monroy, Elibeth; Rodríguez-Moreno, Antonio; Florán, Benjamin; Flores, Gonzalo

    2016-05-01

    Resveratrol may induce its neuroprotective effects by reducing oxidative damage and chronic inflammation apart from improving vascular function and activating longevity genes, it also has the ability to promote the activity of neurotrophic factors. Morphological changes in dendrites of the pyramidal neurons of the prefrontal cortex (PFC) and hippocampus have been reported in the brain of aging humans, or in humans with neurodegenerative diseases such as Alzheimer's disease. These changes are reflected particularly in the decrement of both the dendritic tree and spine density. Here we evaluated the effect of resveratrol on the dendrites of pyramidal neurons of the PFC (Layers 3 and 5), CA1- and CA3-dorsal hippocampus (DH) as well as CA1-ventral hippocampus, dentate gyrus (DG), and medium spiny neurons of the nucleus accumbens of aged rats. 18-month-old rats were administered resveratrol (20 mg/kg, orally) daily for 60 days. Dendritic morphology was studied by the Golgi-Cox stain procedure, followed by Sholl analysis on 20-month-old rats. In all resveratrol-treated rats, a significant increase in dendritic length and spine density in pyramidal neurons of the PFC, CA1, and CA3 of DH was observed. Interestingly, the enhancement in dendritic length was close to the soma in pyramidal neurons of the PFC, whereas in neurons of the DH and DG, the increase in dendritic length was further from the soma. Our results suggest that resveratrol induces modifications of dendritic morphology in the PFC, DH, and DG. These changes may explain the therapeutic effect of resveratrol in aging and in Alzheimer's disease. © 2016 Wiley Periodicals, Inc.

  7. Spatial distribution of intermingling pools of projection neurons with distinct targets: A 3D analysis of the commissural ganglia in Cancer borealis.

    PubMed

    Follmann, Rosangela; Goldsmith, Christopher John; Stein, Wolfgang

    2017-06-01

    Projection neurons play a key role in carrying long-distance information between spatially distant areas of the nervous system and in controlling motor circuits. Little is known about how projection neurons with distinct anatomical targets are organized, and few studies have addressed their spatial organization at the level of individual cells. In the paired commissural ganglia (CoGs) of the stomatogastric nervous system of the crab Cancer borealis, projection neurons convey sensory, motor, and modulatory information to several distinct anatomical regions. While the functions of descending projection neurons (dPNs) which control downstream motor circuits in the stomatogastric ganglion are well characterized, their anatomical distribution as well as that of neurons projecting to the labrum, brain, and thoracic ganglion have received less attention. Using cell membrane staining, we investigated the spatial distribution of CoG projection neurons in relation to all CoG neurons. Retrograde tracing revealed that somata associated with different axonal projection pathways were not completely spatially segregated, but had distinct preferences within the ganglion. Identified dPNs had diameters larger than 70% of CoG somata and were restricted to the most medial and anterior 25% of the ganglion. They were contained within a cluster of motor neurons projecting through the same nerve to innervate the labrum, indicating that soma position was independent of function and target area. Rather, our findings suggest that CoG neurons projecting to a variety of locations follow a generalized rule: for all nerve pathway origins, the soma cluster centroids in closest proximity are those whose axons project down that pathway. © 2017 Wiley Periodicals, Inc.

  8. Circadian Regulation of Hippocampal Long-Term Potentiation

    PubMed Central

    Chaudhury, Dipesh; Wang, Louisa M.; Colwell, Christopher S.

    2008-01-01

    The goal of this study is to investigate the possible circadian regulation of hippocampal excitability and long-term potentiation (LTP) measured by stimulating the Schaffer collaterals (SC) and recording the field excitatory postsynaptic potential (fEPSP) from the CA1 dendritic layer or the population spike (PS) from the soma in brain slices of C3H and C57 mice. These 2 strains of mice were of interest because the C3H mice secrete melatonin rhythmically while the C57 mice do not. The authors found that the magnitude of the enhancement of the PS was significantly greater in LTP recorded from night slices compared to day slices of both C3H and C57 mice. They also found significant diurnal variation in the decay of LTP measured with fEPSPs, with the decay slower during the night in both strains of mice. There was evidence for a diurnal rhythm in the input/output function of pyramidal neurons measured at the soma in C57 but not C3H mice. Furthermore, LTP in the PS, measured in slices prepared during the day but recorded during the night, had a profile remarkably similar to the night group. Finally, PS recordings were carried out in slices from C3H mice maintained in constant darkness prior to experimentation. Again, the authors found that the magnitude of the enhancement of the PS was significantly greater in LTP recorded from subjective night slices compared to subjective day slices. These results provide the 1st evidence that an endogenous circadian oscillator modulates synaptic plasticity in the hippocampus. PMID:15851529

  9. Total Mucosal Irradiation with Intensity-modulated Radiotherapy in Patients with Head and Neck Carcinoma of Unknown Primary: A Pooled Analysis of Two Prospective Studies.

    PubMed

    Richards, T M; Bhide, S A; Miah, A B; Del Rosario, L; Bodla, S; Thway, K; Gujral, D M; Rooney, K P; Schick, U; McGovern, T; Grove, L; Newbold, K L; Harrington, K J; Nutting, C M

    2016-09-01

    To determine the clinical outcomes of an intensity-modulated radiotherapy technique for total mucosal irradiation (TM-IMRT) in patients with head and neck carcinoma of unknown primary (HNCUP). A single-centre prospective phase II trial design was used in two sequential studies to evaluate TM-IMRT for HNCUP. Patients were investigated for primary tumour site using examination under anaesthetic and biopsies, computed tomography ± magnetic resonance imaging (MRI) or 18-fluorodeoxyglucose positron emission tomography-computed tomography (PET-CT). Patients received IMRT to the potential primary tumour sites and elective cervical nodes. Concomitant chemotherapy was used in patients who received primary radiotherapy or those with nodal extracapsular extension. Thirty-six patients with HNCUP were recruited; 72% male. Twenty-five patients (69.4%) had p16-positive disease. Two year mucosal and local nodal control rates were 97.1% (95% confidence interval 91.4-100) and 89.8% (78.4-100), respectively. One mucosal primary was detected 7.3 months after TM-IMRT and three patients died from recurrent/metastatic squamous cell carcinoma of the head and neck. Twelve patients (33%) developed grade 3 (Late Effects in Normal Tissue-Subjective, Objective, Management and Analytical; LENT-SOMA) dysphagia with a 1 year enteric tube feeding rate of 2.7%. The high-grade subjective xerostomia rate (LENT-SOMA) at 24 months after IMRT was 15%. At a median follow-up of 36.1 months, the use of TM-IMRT was associated with good local control. Toxicity was comparable with previously reported TM-IMRT regimens encompassing similar mucosal volumes. Copyright © 2016 The Royal College of Radiologists. Published by Elsevier Ltd. All rights reserved.

  10. Opposite optimal current flow directions for induction of neuroplasticity and excitation threshold in the human motor cortex.

    PubMed

    Sommer, Martin; Norden, Christoph; Schmack, Lars; Rothkegel, Holger; Lang, Nicolas; Paulus, Walter

    2013-05-01

    Directional sensitivity is relevant for the excitability threshold of the human primary motor cortex, but its importance for externally induced plasticity is unknown. To study the influence of current direction on two paradigms inducing neuroplasticity by repetitive transcranial magnetic stimulation (rTMS). We studied short-lasting after-effects induced in the human primary motor cortex of 8 healthy subjects, using 5 Hz rTMS applied in six blocks of 200 pulses each, at 90% active motor threshold. We controlled for intensity, frequency, waveform and spinal effects. Only biphasic pulses with the effective component delivered in an anterioposterior direction (henceforth posteriorly directed) in the brain yielded an increase of motor-evoked potential (MEP) amplitudes outlasting rTMS. MEP latencies and F-wave amplitudes remained unchanged. Biphasic pulses directed posteroanterior (i.e. anteriorly) were ineffective, as were monophasic pulses from either direction. A 1 Hz study in a group of 12 healthy subjects confirmed facilitation after posteriorly directed biphasic pulses only. The anisotropy of the human primary motor cortex is relevant for induction of plasticity by subtreshold rTMS, with a current flow opposite to that providing lowest excitability thresholds. This is consistent with the idea of TMS primarily targeting cortical columns of the phylogenetically new M1 in the anterior bank of the central sulcus. For these, anteriorly directed currents are soma-depolarizing, therefore optimal for low thresholds, whereas posteriorly directed currents are soma-hyperpolarizing, likely dendrite-depolarizing and bested suited for induction of plasticity. Our findings should help focus and enhance rTMS effects in experimental and clinical settings. Copyright © 2013 Elsevier Inc. All rights reserved.

  11. Faster voltage-dependent activation of Na+ channels in growth cones versus somata of neuroblastoma N1E-115 cells.

    PubMed Central

    Zhang, J; Loew, L M; Davidson, R M

    1996-01-01

    Kinetics of voltage-gated ionic channels fundamentally reflect the response of the channels to local electric fields. In this report cell-attached patch-clamp studies reveal that the voltage-dependent activation rate of sodium channels residing in the growth cone membrane differs from that of soma sodium channels in differentiating N1E-115 neuroblastoma cells. Because other electrophysiological properties of these channels do not differ, this finding may be a reflection of the difference in intramembrane electric field in these two regions of the cell. This represents a new mechanism for channels to attain a range of activities both within and between cells. PMID:8913589

  12. Faster voltage-dependent activation of Na+ channels in growth cones versus somata of neuroblastoma N1E-115 cells.

    PubMed

    Zhang, J; Loew, L M; Davidson, R M

    1996-11-01

    Kinetics of voltage-gated ionic channels fundamentally reflect the response of the channels to local electric fields. In this report cell-attached patch-clamp studies reveal that the voltage-dependent activation rate of sodium channels residing in the growth cone membrane differs from that of soma sodium channels in differentiating N1E-115 neuroblastoma cells. Because other electrophysiological properties of these channels do not differ, this finding may be a reflection of the difference in intramembrane electric field in these two regions of the cell. This represents a new mechanism for channels to attain a range of activities both within and between cells.

  13. Do yogis have “Learning Styles”? (A somatic solution)

    PubMed Central

    Strean, William Ben

    2017-01-01

    Background: Learning styles has captivated a great deal of attention in yoga teacher training. The triad of visual, auditory, and kinesthetic learning styles has been particularly popular; yet as Sharp et al. asserted, such an approach trivializes the complexity of learning and compromises scholarship at all levels of the education community. Aims: This paper addresses that although there is great merit in recognizing yoga students’ differences and preferences, many uses of learning styles in yoga teacher training are superficial and promote self-handicapping. Conclusion: A somatic perspective (from soma, the body in its wholeness) offers a framework to reconsider the depth of effective learning. PMID:28149066

  14. An immunoelectron microscopic study of methionine-enkephalin structures in cat prevertebral ganglia.

    PubMed

    Benfares, J; Henry, M; Cupo, A; Julé, Y

    1995-03-01

    Methionine-enkephalin-like immunoreactivity was detected in presynaptic nerve fibers and SIF cells in cat prevertebral ganglia. The immunoreactive nerve fibers contained a mixture of numerous small clear vesicles and a few large vesicles; the immunoreactivity was only confined to the large vesicles. Most of the immunoreactive fibers were in apposition with non-immunoreactive neuronal profiles, without any detectable synaptic membrane specializations. The other immunoreactive fibers formed synaptic contacts mainly with non-immunostained dendrites and to a lesser extent with axons and neuronal soma. The characterization at the ultrastructural level of the enkephalin-like immunoreactive structures is discussed as regards the modalities whereby opiates may be involved in sympathetic ganglionic transmission.

  15. Mammalian sex chromosomes. III. Activity of pseudoautosomal steroid sulfatase enzyme during spermatogenesis in Mus musculus.

    PubMed

    Raman, R; Das, P

    1991-09-01

    Parallel to the inactivation of the X chromosome in somatic cells of female, the male X in mammals is rendered inactive during spermatogenesis. Pseudoautosomal genes, those present on the X-Y meiotically pairable region of male, escape inactivation in female soma. It is suggested, but not demonstrated, that they may also be refractory to the inactivation signal in male germ cells. We have assayed activity of the enzyme steroid sulfatase, product of a pseudoautosomal gene, in testicular cells of the mouse and shown its presence in premeiotic, meiotic (pachytene), and postmeiotic (spermatid) cell types. It appears that, as in females, pseudoautosomal genes may escape inactivation in male germ cells also.

  16. Optimal combination of minimum degrees of freedom to be actuated in the lower limbs to facilitate arm-free paraplegic standing.

    PubMed

    Kim, Joon-Young; Mills, James K; Vette, Albert H; Popovic, Milos R

    2007-12-01

    Arm-free paraplegic standing via functional electrical stimulation (FES) has drawn much attention in the biomechanical field as it might allow a paraplegic to stand and simultaneously use both arms to perform daily activities. However, current FES systems for standing require that the individual actively regulates balance using one or both arms, thus limiting the practical use of these systems. The purpose of the present study was to show that actuating only six out of 12 degrees of freedom (12-DOFs) in the lower limbs to allow paraplegics to stand freely is theoretically feasible with respect to multibody stability and physiological torque limitations of the lower limb DOF. Specifically, the goal was to determine the optimal combination of the minimum DOF that can be realistically actuated using FES while ensuring stability and able-bodied kinematics during perturbed arm-free standing. The human body was represented by a three-dimensional dynamics model with 12-DOFs in the lower limbs. Nakamura's method (Nakamura, Y., and Ghodoussi, U., 1989, "Dynamics Computation of Closed-Link Robot Mechanisms With Nonredundant and Redundant Actuators," IEEE Trans. Rob. Autom., 5(3), pp. 294-302) was applied to estimate the joint torques of the system using experimental motion data from four healthy subjects. The torques were estimated by applying our previous finding that only 6 (6-DOFs) out of 12-DOFs in the lower limbs need to be actuated to facilitate stable standing. Furthermore, it was shown that six cases of 6-DOFs exist, which facilitate stable standing. In order to characterize each of these cases in terms of the torque generation patterns and to identify a potential optimal 6-DOF combination, the joint torques during perturbations in eight different directions were estimated for all six cases of 6-DOFs. The results suggest that the actuation of both ankle flexionextension, both knee flexionextension, one hip flexionextension, and one hip abductionadduction DOF will

  17. Frontiers in Numerical Relativity

    NASA Astrophysics Data System (ADS)

    Evans, Charles R.; Finn, Lee S.; Hobill, David W.

    2011-06-01

    Preface; Participants; Introduction; 1. Supercomputing and numerical relativity: a look at the past, present and future David W. Hobill and Larry L. Smarr; 2. Computational relativity in two and three dimensions Stuart L. Shapiro and Saul A. Teukolsky; 3. Slowly moving maximally charged black holes Robert C. Ferrell and Douglas M. Eardley; 4. Kepler's third law in general relativity Steven Detweiler; 5. Black hole spacetimes: testing numerical relativity David H. Bernstein, David W. Hobill and Larry L. Smarr; 6. Three dimensional initial data of numerical relativity Ken-ichi Oohara and Takashi Nakamura; 7. Initial data for collisions of black holes and other gravitational miscellany James W. York, Jr.; 8. Analytic-numerical matching for gravitational waveform extraction Andrew M. Abrahams; 9. Supernovae, gravitational radiation and the quadrupole formula L. S. Finn; 10. Gravitational radiation from perturbations of stellar core collapse models Edward Seidel and Thomas Moore; 11. General relativistic implicit radiation hydrodynamics in polar sliced space-time Paul J. Schinder; 12. General relativistic radiation hydrodynamics in spherically symmetric spacetimes A. Mezzacappa and R. A. Matzner; 13. Constraint preserving transport for magnetohydrodynamics John F. Hawley and Charles R. Evans; 14. Enforcing the momentum constraints during axisymmetric spacelike simulations Charles R. Evans; 15. Experiences with an adaptive mesh refinement algorithm in numerical relativity Matthew W. Choptuik; 16. The multigrid technique Gregory B. Cook; 17. Finite element methods in numerical relativity P. J. Mann; 18. Pseudo-spectral methods applied to gravitational collapse Silvano Bonazzola and Jean-Alain Marck; 19. Methods in 3D numerical relativity Takashi Nakamura and Ken-ichi Oohara; 20. Nonaxisymmetric rotating gravitational collapse and gravitational radiation Richard F. Stark; 21. Nonaxisymmetric neutron star collisions: initial results using smooth particle hydrodynamics

  18. Signatures of cosmic-ray increase attributed to exceptional solar storms inferred from multiple cosmogenic radionuclide records

    NASA Astrophysics Data System (ADS)

    Mekhaldi, Florian; Muscheler, Raimund; Adolphi, Florian; Svensson, Anders; Aldahan, Ala; Possnert, Göran; McConnell, Joseph R.; Sigl, Michael; Welten, Kees C.; Woodruff, Thomas E.

    2014-05-01

    Miyake et al. (2012, 2013) discovered rapid increases of 14C content in tree rings dated to AD 774-5 and AD 993-4 which they have attributed to cosmic-ray events. These extreme particle events have no counterparts in the instrumental record and have been tentatively associated with solar proton events, supernovae and short gamma-ray bursts, which have very different energy spectra. Cosmogenic radionuclides such as 14C, 10Be and 36Cl arise from the interaction of cosmic rays with atmospheric nitrogen, oxygen and argon. These radio-isotopes are produced through different reaction pathways and vary with different energy dependencies of the production rate cross section. Owing to this, yield functions can be used to determine the energy level of incident particles. However, only 14C has been measured at high resolution to quantify the energy and thus the origin of the outbursts. We present an annually resolved record of 10Be from the NGRIP ice core for the two events. In addition, we also utilized the GRIP ice core 36Cl record in our analysis. Our results show that the differential production of cosmogenic 14C, 10Be and 36Cl is consistent with a solar energy spectrum. Considering the notable increase in radionuclides, the solar storms would have had to be substantially greater than the largest recorded geomagnetic storm, the so-called Carrington event. This challenges our understanding of the sun's dynamics. Furthermore, the events could possibly be of interest for the investigation of potential cosmic ray-cloud linkages (Svensmark & Friis-Christensen, 1997). Alternatively, such outbursts of energetic particles have the potential to deplete atmospheric ozone and alter atmospheric circulation. Ultimately, the magnitude of such particle events draws attention to the perhaps underestimated potential of the sun to cause great damage to modern technologies. References Miyake, F., Masuda, K. & Nakamura, T. Another rapid event in the carbon-14 content of tree rings. Nature

  19. Approaches to Numerical Relativity

    NASA Astrophysics Data System (ADS)

    d'Inverno, Ray

    2005-07-01

    Introduction Ray d'Inverno; Preface C. J. S. Clarke; Part I. Theoretical Approaches: 1. Numerical relativity on a transputer array Ray d'Inverno; 2. Some aspects of the characteristic initial value problem in numerical relativity Nigel Bishop; 3. The characteristic initial value problem in general relativity J. M. Stewart; 4. Algebraic approachs to the characteristic initial value problem in general relativity Jõrg Frauendiener; 5. On hyperboidal hypersurfaces Helmut Friedrich; 6. The initial value problem on null cones J. A. Vickers; 7. Introduction to dual-null dynamics S. A. Hayward; 8. On colliding plane wave space-times J. B. Griffiths; 9. Boundary conditions for the momentum constraint Niall O Murchadha; 10. On the choice of matter model in general relativity A. D. Rendall; 11. A mathematical approach to numerical relativity J. W. Barrett; 12. Making sense of the effects of rotation in general relativity J. C. Miller; 13. Stability of charged boson stars and catastrophe theory Franz E. Schunck, Fjodor V. Kusmartsev and Eckehard W. Mielke; Part II. Practical Approaches: 14. Numerical asymptotics R. Gómez and J. Winicour; 15. Instabilities in rapidly rotating polytropes Scott C. Smith and Joan M. Centrella; 16. Gravitational radiation from coalescing binary neutron stars Ken-Ichi Oohara and Takashi Nakamura; 17. 'Critical' behaviour in massless scalar field collapse M. W. Choptuik; 18. Goudunov-type methods applied to general relativistic gravitational collapse José Ma. Ibánez, José Ma. Martí, Juan A. Miralles and J. V. Romero; 19. Astrophysical sources of gravitational waves and neutrinos Silvano Bonazzola, Eric Gourgoulhon, Pawel Haensel and Jean-Alain Marck; 20. Gravitational radiation from triaxial core collapse Jean-Alain Marck and Silvano Bonazzola; 21. A vacuum fully relativistic 3D numerical code C. Bona and J. Massó; 22. Solution of elliptic equations in numerical relativity using multiquadrics M. R. Dubal, S. R. Oliveira and R. A. Matzner; 23

  20. Reliable, responsive pacemaking and pattern generation with minimal cell numbers: the crustacean cardiac ganglion.

    PubMed

    Cooke, Ian M

    2002-04-01

    Investigations of the electrophysiology of crustacean cardiac ganglia over the last half-century are reviewed for their contributions to elucidating the cellular mechanisms and interactions by which a small (as few as nine cells) neuronal network accomplishes extremely reliable, rhythmical, patterned activation of muscular activity-in this case, beating of the neurogenic heart. This ganglion is thus a model for pacemaking and central pattern generation. Favorable anatomy has permitted voltage- and space-clamp analyses of voltage-dependent ionic currents that endow each neuron with the intrinsic ability to respond with rhythmical, patterned impulse activity to nonpatterned stimulation. The crustacean soma and initial axon segment do not support impulse generation but integrate input from stretch-sensitive dendrites and electrotonic and chemically mediated synapses on axonal processes in neuropils. The soma and initial axon produce a depolarization-activated, calcium-mediated, sustained potential, the "driver potential," so-called because it drives a train of impulses at the "trigger zone" of the axon. Extreme reliability results from redundancy and the electrotonic coupling and synaptic interaction among all the neurons. Complex modulation by central nervous system inputs and by neurohormones to adjust heart pumping to physiological demands has long been demonstrated, but much remains to be learned about the cellular and molecular mechanisms of action. The continuing relevance of the crustacean cardiac ganglion as a relatively simple model for pacemaking and central pattern generation is confirmed by the rapidly widening documentation of intrinsic potentials such as plateau potentials in neurons of all major animal groups. The suite of ionic currents (a slowly inactivating calcium current and various potassium currents, with variations) observed for the crustacean cardiac ganglion have been implicated in or proven to underlie a majority of the intrinsic potentials

  1. Quinolinic acid induces neuritogenesis in SH-SY5Y neuroblastoma cells independently of NMDA receptor activation.

    PubMed

    Hernandez-Martinez, Juan-Manuel; Forrest, Caroline M; Darlington, L Gail; Smith, Robert A; Stone, Trevor W

    2017-03-01

    Glutamate and nicotinamide adenine dinucleotide (NAD + ) have been implicated in neuronal development and several types of cancer. The kynurenine pathway of tryptophan metabolism includes quinolinic acid (QA) which is both a selective agonist at N-methyl-D-aspartate (NMDA) receptors and also a precursor for the formation of NAD + . The effect of QA on cell survival and differentiation has therefore been examined on SH-SY5Y human neuroblastoma cells. Retinoic acid (RA, 10 μm) induced differentiation of SH-SY5Y cells into a neuronal phenotype showing neurite growth. QA (50-150 nm) also caused a concentration-dependent increase in the neurite/soma ratio, indicating differentiation. Both RA and QA increased expression of the neuronal marker β3-tubulin in whole-cell homogenates and in the neuritic fraction assessed using a neurite outgrowth assay. Expression of the neuronal proliferation marker doublecortin revealed that, unlike RA, QA did not decrease the number of mitotic cells. QA-induced neuritogenesis coincided with an increase in the generation of reactive oxygen species. Neuritogenesis was prevented by diphenylene-iodonium (an inhibitor of NADPH oxidase) and superoxide dismutase, supporting the involvement of reactive oxygen species. NMDA itself did not promote neuritogenesis and the NMDA antagonist dizocilpine (MK-801) did not prevent quinolinate-induced neuritogenesis, indicating that the effects of QA were independent of NMDA receptors. Nicotinamide caused a significant increase in the neurite/soma ratio and the expression of β3-tubulin in the neuritic fraction. Taken together, these results suggest that QA induces neuritogenesis by promoting oxidizing conditions and affecting the availability of NAD + , independently of NMDA receptors. © 2016 Federation of European Neuroscience Societies and John Wiley & Sons Ltd.

  2. Impact of Morphometry, Myelinization and Synaptic Current Strength on Spike Conduction in Human and Cat Spiral Ganglion Neurons

    PubMed Central

    Rattay, Frank; Potrusil, Thomas; Wenger, Cornelia; Wise, Andrew K.; Glueckert, Rudolf; Schrott-Fischer, Anneliese

    2013-01-01

    Background Our knowledge about the neural code in the auditory nerve is based to a large extent on experiments on cats. Several anatomical differences between auditory neurons in human and cat are expected to lead to functional differences in speed and safety of spike conduction. Methodology/Principal Findings Confocal microscopy was used to systematically evaluate peripheral and central process diameters, commonness of myelination and morphology of spiral ganglion neurons (SGNs) along the cochlea of three human and three cats. Based on these morphometric data, model analysis reveales that spike conduction in SGNs is characterized by four phases: a postsynaptic delay, constant velocity in the peripheral process, a presomatic delay and constant velocity in the central process. The majority of SGNs are type I, connecting the inner hair cells with the brainstem. In contrast to those of humans, type I neurons of the cat are entirely myelinated. Biophysical model evaluation showed delayed and weak spikes in the human soma region as a consequence of a lack of myelin. The simulated spike conduction times are in accordance with normal interwave latencies from auditory brainstem response recordings from man and cat. Simulated 400 pA postsynaptic currents from inner hair cell ribbon synapses were 15 times above threshold. They enforced quick and synchronous spiking. Both of these properties were not present in type II cells as they receive fewer and much weaker (∼26 pA) synaptic stimuli. Conclusions/Significance Wasting synaptic energy boosts spike initiation, which guarantees the rapid transmission of temporal fine structure of auditory signals. However, a lack of myelin in the soma regions of human type I neurons causes a large delay in spike conduction in comparison with cat neurons. The absent myelin, in combination with a longer peripheral process, causes quantitative differences of temporal parameters in the electrically stimulated human cochlea compared to the cat

  3. Radiation Therapy Did Not Induce Long-Term Changes in Rectal Mucosa: Results From the Randomized Scandinavian Prostate Cancer Group 7 Trial

    DOE Office of Scientific and Technical Information (OSTI.GOV)

    Slagsvold, Jens Erik, E-mail: Jens.Erik.Slagsvold@stolav.no; Viset, Trond; Wibe, Arne

    Purpose: To investigate long-term changes in the rectal mucosa after curative external beam radiation therapy in the treatment of prostate cancer. Methods and Materials: In the Scandinavian Prostate Cancer Group 7 trial, 880 men with locally advanced prostate cancer were randomized to hormonal therapy alone versus hormonal therapy plus radiation therapy to 70 Gy. A subcohort from this trial being randomized at our center (n=178) was invited to a study on late anorectal side effects during 2003-2005, approximately 5 years after treatment, including measuring health-reported quality of life and physician-assessed toxicity score by the Late Effects Normal Tissue Task Force/Subjective, Objective, Management, Analyticmore » (LENT/SOMA) and European Organization for Research and Treatment of Cancer/Radiation Therapy Oncology Group score. Sixty-seven patients had a rectal mucosa biopsy. Sixty-four biopsies were included in the final analysis, of which 33 patients were randomized to hormonal treatment and 31 to hormonal treatment plus radiation therapy. The presence of fibrosis, number of capillaries, and lymphocyte infiltration was then evaluated by light microscopy. Results: The group receiving radiation therapy had significantly higher LENT/SOMA and function/bother scale scores than the group that only received hormonal treatment, but there was no significant difference in the presence of fibrosis, ectasia, number of capillaries in the lamina propria, or lymphocyte infiltration between the groups. Conclusion: Radiation therapy to 70 Gy to the prostate does not induce long-term microscopic mucosal changes in the rectum 5 years after treatment. This is in contrast to the general assumption that structural changes, including fibrosis, seen after radiation therapy include the mucosa. We speculate that the main late effects of radiation therapy on the structure of the rectum are located in the deeper layers of the rectal wall than the mucosa.« less

  4. Developmental Activation of the Proteolipid Protein Promoter Transgene in Neuronal and Oligodendroglial Cells of Neostriatum in Mice

    PubMed Central

    Fulton, Daniel; Paez, Pablo; Spreur, Vilma; Handley, Vance; Colwell, Christopher S.; Campagnoni, Anthony; Fisher, Robin

    2011-01-01

    Prior studies suggest that non-canonical proteolipid protein (PLP) gene expression occurs during development in non-myelinating neurons as well as myelinating oligodendroglia in mammalian brain. To assess this possibility in neostriatum, a region of uncertain PLP gene expression in neurons, morphological and electrophysiological tools were used to determine phenotypes of cells with activation of a PLP promoter transgene during the early postnatal period in mice. PLP gene expression is evident in both neuronal and oligodendroglial phenotypes in developing neostriatum, a conclusion based on three novel observations: (1) An enhanced green fluorescent protein (EGFP) reporter of PLP promoter activation was localized in two distinct populations of cells, which exhibit collective, developmental differences of morphological and electrophysiological characteristics in accord with neuronal and oligodendroglial phenotypes of neostriatal cells found during the early postnatal period in both transgenic and wild-type mice. (2) The EGFP reporter of PLP promoter activation was appropriately positioned to serve as a regulator of PLP gene expression. It colocalized with native PLP proteins in both neuronal and oligodendroglial phenotypes; however, only soma-restricted PLP protein isoforms were found in the neuronal phenotype, while classic and soma-restricted PLP protein isoforms were found in the oligodendroglial phenotype. (3) As shown by EGFP reporter, PLP promoter activation was placed to regulate PLP gene expression in only one neuronal phenotype among the several that constitute neostriatum. It was localized in medium spiny neurons, but not large aspiny neurons. These outcomes have significant implications for the non-canonical functional roles of PLP gene expression in addition to myelinogenesis in mammalian brain, and are consistent with potentially independent pathologic loci in neurons during the course of human mutational disorders of PLP gene expression. PMID:21912090

  5. Effect of edaravone on radiation-induced brain necrosis in patients with nasopharyngeal carcinoma after radiotherapy: a randomized controlled trial.

    PubMed

    Tang, Yamei; Rong, Xiaoming; Hu, Weihan; Li, Guoqian; Yang, Xiaoxia; Yang, Jianhua; Xu, Pengfei; Luo, Jinjun

    2014-11-01

    Excessive generation of free radicals plays a critical role in the pathogenesis of radiation-induced brain injury. This study was designed to evaluate the protective effect of edaravone, a free radical scavenger, on radiation-induced brain necrosis in patients with nasopharyngeal carcinoma. Eligible patients were randomized 1:1 to the control group and the edaravone group (intravenous 30 mg twice per day for 2 weeks). Both groups received intravenous conventional steroid therapy and were monitored by brain MRI and LENT/SOMA scales prior to the entry of the trial and at 3-months after completing the trial. The primary end point was a 3-month response rate of the proportional changes determined by MRI. The trial is registered at Clinicaltrials.gov Identifier: NCT01865201. Between 2009 and 2012, we enrolled 154 patients. Of whom 137 were eligible for analysis. The volumes of necrosis estimated on T(2)-weighted image showed that 55.6 % edaravone-treated patients (40 out of 72) showed edema decreases ≥25 %, which was significantly higher than that in the control group (35.4 %, 23 out of 65, p = 0.025). Forty-four patients treated with edaravone (61.1 %) reported improvement in neurologic symptoms and signs evaluated by LENT/SOMA scales, while the rate was 38.5 % in the control group (p = 0.006). MRI of the edaravone group showed a significant decrease in area of T(1)-weighted contrast enhancement (1.67 ± 4.69 cm(2), p = 0.004) and the T(2)-weighted edema (5.08 ± 10.32 cm(2), p = 0.000). Moreover, compared with those in control group, patients with edaravone exhibited significantly better radiological improvement measured by T(2)-weighted image (p = 0.042). Administration of edaravone, in adjunct to steroid regimen, might provide a better outcome in patients with radiation-induced brain necrosis.

  6. Dendritic spikes amplify the synaptic signal to enhance detection of motion in a simulation of the direction-selective ganglion cell.

    PubMed

    Schachter, Michael J; Oesch, Nicholas; Smith, Robert G; Taylor, W Rowland

    2010-08-19

    The On-Off direction-selective ganglion cell (DSGC) in mammalian retinas responds most strongly to a stimulus moving in a specific direction. The DSGC initiates spikes in its dendritic tree, which are thought to propagate to the soma with high probability. Both dendritic and somatic spikes in the DSGC display strong directional tuning, whereas somatic PSPs (postsynaptic potentials) are only weakly directional, indicating that spike generation includes marked enhancement of the directional signal. We used a realistic computational model based on anatomical and physiological measurements to determine the source of the enhancement. Our results indicate that the DSGC dendritic tree is partitioned into separate electrotonic regions, each summing its local excitatory and inhibitory synaptic inputs to initiate spikes. Within each local region the local spike threshold nonlinearly amplifies the preferred response over the null response on the basis of PSP amplitude. Using inhibitory conductances previously measured in DSGCs, the simulation results showed that inhibition is only sufficient to prevent spike initiation and cannot affect spike propagation. Therefore, inhibition will only act locally within the dendritic arbor. We identified the role of three mechanisms that generate directional selectivity (DS) in the local dendritic regions. First, a mechanism for DS intrinsic to the dendritic structure of the DSGC enhances DS on the null side of the cell's dendritic tree and weakens it on the preferred side. Second, spatially offset postsynaptic inhibition generates robust DS in the isolated dendritic tips but weak DS near the soma. Third, presynaptic DS is apparently necessary because it is more robust across the dendritic tree. The pre- and postsynaptic mechanisms together can overcome the local intrinsic DS. These local dendritic mechanisms can perform independent nonlinear computations to make a decision, and there could be analogous mechanisms within cortical circuitry.

  7. Inner tegument proteins of Herpes Simplex Virus are sufficient for intracellular capsid motility in neurons but not for axonal targeting

    PubMed Central

    Müller, Oliver; Ivanova, Lyudmila; Bialy, Dagmara; Pohlmann, Anja; Binz, Anne; Hegemann, Maike; Viejo-Borbolla, Abel; Rosenhahn, Bodo; Bauerfeind, Rudolf; Sodeik, Beate

    2017-01-01

    Upon reactivation from latency and during lytic infections in neurons, alphaherpesviruses assemble cytosolic capsids, capsids associated with enveloping membranes, and transport vesicles harboring fully enveloped capsids. It is debated whether capsid envelopment of herpes simplex virus (HSV) is completed in the soma prior to axonal targeting or later, and whether the mechanisms are the same in neurons derived from embryos or from adult hosts. We used HSV mutants impaired in capsid envelopment to test whether the inner tegument proteins pUL36 or pUL37 necessary for microtubule-mediated capsid transport were sufficient for axonal capsid targeting in neurons derived from the dorsal root ganglia of adult mice. Such neurons were infected with HSV1-ΔUL20 whose capsids recruited pUL36 and pUL37, with HSV1-ΔUL37 whose capsids associate only with pUL36, or with HSV1-ΔUL36 that assembles capsids lacking both proteins. While capsids of HSV1-ΔUL20 were actively transported along microtubules in epithelial cells and in the somata of neurons, those of HSV1-ΔUL36 and -ΔUL37 could only diffuse in the cytoplasm. Employing a novel image analysis algorithm to quantify capsid targeting to axons, we show that only a few capsids of HSV1-ΔUL20 entered axons, while vesicles transporting gD utilized axonal transport efficiently and independently of pUL36, pUL37, or pUL20. Our data indicate that capsid motility in the somata of neurons mediated by pUL36 and pUL37 does not suffice for targeting capsids to axons, and suggest that capsid envelopment needs to be completed in the soma prior to targeting of herpes simplex virus to the axons, and to spreading from neurons to neighboring cells. PMID:29284065

  8. Miro's N-Terminal GTPase Domain Is Required for Transport of Mitochondria into Axons and Dendrites

    PubMed Central

    Babic, Milos; Russo, Gary J.; Wellington, Andrea J.; Sangston, Ryan M.; Gonzalez, Migdalia

    2015-01-01

    Mitochondria are dynamically transported in and out of neuronal processes to maintain neuronal excitability and synaptic function. In higher eukaryotes, the mitochondrial GTPase Miro binds Milton/TRAK adaptor proteins linking microtubule motors to mitochondria. Here we show that Drosophila Miro (dMiro), which has previously been shown to be required for kinesin-driven axonal transport, is also critically required for the dynein-driven distribution of mitochondria into dendrites. In addition, we used the loss-of-function mutations dMiroT25N and dMiroT460N to determine the significance of dMiro's N-terminal and C-terminal GTPase domains, respectively. Expression of dMiroT25N in the absence of endogenous dMiro caused premature lethality and arrested development at a pupal stage. dMiroT25N accumulated mitochondria in the soma of larval motor and sensory neurons, and prevented their kinesin-dependent and dynein-dependent distribution into axons and dendrites, respectively. dMiroT25N mutant mitochondria also were severely fragmented and exhibited reduced kinesin and dynein motility in axons. In contrast, dMiroT460N did not impair viability, mitochondrial size, or the distribution of mitochondria. However, dMiroT460N reduced dynein motility during retrograde mitochondrial transport in axons. Finally, we show that substitutions analogous to the constitutively active Ras-G12V mutation in dMiro's N-terminal and C-terminal GTPase domains cause neomorphic phenotypic effects that are likely unrelated to the normal function of each GTPase domain. Overall, our analysis indicates that dMiro's N-terminal GTPase domain is critically required for viability, mitochondrial size, and the distribution of mitochondria out of the neuronal soma regardless of the employed motor, likely by promoting the transition from a stationary to a motile state. PMID:25855186

  9. Evidence for structural plasticity in the supraoptic nucleus of the rat hypothalamus in relation to gestation and lactation.

    PubMed

    Theodosis, D T; Poulain, D A

    1984-01-01

    Supraoptic nuclei of lactating rats present a particular anatomical organization that could serve to facilitate the synchronization of neuronal firing observed during suckling-induced reflex milk ejections. Although magnocellular neurones are usually separated by neuropil elements, particularly glial fibers, in lactating rats, numerous neurosecretory soma and dendritic profiles are in direct apposition, without glial interposition. Concomitantly, there is also a higher incidence of presynaptic terminals contacting two neurosecretory elements in the same plane of section ("double" synapses). In the present study, a quantitative ultrastructural analysis was used to trace the evolution of the structural reorganization of the nucleus at different stages of the reproductive cycle. The percentage of neurosecretory soma and dendritic profiles in direct apposition was low two weeks after the beginning of pregnancy, but the day prior to parturition, as during lactation, over 40% of all neurosecretory profiles were directly in contact and involved about 10% of the total neuronal surface membrane measured (a 5-fold increase over the corresponding frequencies recorded in virgin rats at oestrus). The contiguous neuronal membranes and associated intercellular space appeared unmodified, except for the presence of attachment plaques, that also increased in frequency at late gestation and lactation. The incidence of "double" synapses also increased by late gestation, so that at lactation, they bridged 8% of all the recorded neurosecretory somata and dendrites, (as compared to 1% in the virgin rats). Similar changes were observed during a first and second gestation and lactation. The incidence of direct appositions and "double" synapses then diminished gradually after weaning: 2 months after the end of lactation, the ultrastructure of the nucleus resembled that of virgin animals. These observations demonstrate a plasticity in the structural organization of the supraoptic nucleus

  10. Zen and the brain: mutually illuminating topics.

    PubMed

    Austin, James H

    2013-10-24

    Zen Buddhist meditative practices emphasize the long-term, mindful training of attention and awareness during one's ordinary daily-life activities, the shedding of egocentric behaviors, and the skillful application of one's innate compassionate resources of insight-wisdom toward others and oneself. This review focuses on how such a comprehensive approach to training the brain could relate to a distinctive flavor of Zen: its emphasis on direct experience, with special reference to those major acute states of awakening that create deep transformations of consciousness and behavior. In Japanese, these advanced states are called kensho and satori. Ten key concepts are reviewed. They begin by distinguishing between the concentrative and receptive forms of meditation, noticing the complementary ways that they each train our normal "top-down" and "bottom-up" modes of attentive processing. Additional concepts distinguish between our two major processing pathways. The self-centered, egocentric frame of reference processes information in relation to our body (our soma) or to our mental functions (our psyche). The other-centered frame of reference processes information anonymously. Its prefix, allo- simply means "other" in Greek. Subsequent concepts consider how these useful Greek words-ego/allo, soma/psyche-correlate with the normal functional anatomy of important thalamo ↔ cortical connections. A plausible model then envisions how a triggering stimulus that captures attention could prompt the reticular nucleus to release GABA; how its selective inhibition of the dorsal thalamus could then block both our higher somatic and psychic cortical functions; so as to: (a) delete the maladaptive aspects of selfhood, while also (b) releasing the direct, all-inclusive, globally-unified experience of other. Two final concepts consider how the long-term meditative training of intuitive functions relates to certain kinds of word-free spatial tasks that involve insightful creative

  11. Feedforward and feedback inhibition in neostriatal GABAergic spiny neurons.

    PubMed

    Tepper, James M; Wilson, Charles J; Koós, Tibor

    2008-08-01

    There are two distinct inhibitory GABAergic circuits in the neostriatum. The feedforward circuit consists of a relatively small population of GABAergic interneurons that receives excitatory input from the neocortex and exerts monosynaptic inhibition onto striatal spiny projection neurons. The feedback circuit comprises the numerous spiny projection neurons and their interconnections via local axon collaterals. This network has long been assumed to provide the majority of striatal GABAergic inhibition and to sharpen and shape striatal output through lateral inhibition, producing increased activity in the most strongly excited spiny cells at the expense of their less strongly excited neighbors. Recent results, mostly from recording experiments of synaptically connected pairs of neurons, have revealed that the two GABAergic circuits differ markedly in terms of the total number of synapses made by each, the strength of the postsynaptic response detected at the soma, the extent of presynaptic convergence and divergence and the net effect of the activation of each circuit on the postsynaptic activity of the spiny neuron. These data have revealed that the feedforward inhibition is powerful and widespread, with spiking in a single interneuron being capable of significantly delaying or even blocking the generation of spikes in a large number of postsynaptic spiny neurons. In contrast, the postsynaptic effects of spiking in a single presynaptic spiny neuron on postsynaptic spiny neurons are weak when measured at the soma, and unable to significantly affect spike timing or generation. Further, reciprocity of synaptic connections between spiny neurons is only rarely observed. These results suggest that the bulk of the fast inhibition that has the strongest effects on spiny neuron spike timing comes from the feedforward interneuronal system whereas the axon collateral feedback system acts principally at the dendrites to control local excitability as well as the overall level of

  12. Modelling the Effects of Electrical Coupling between Unmyelinated Axons of Brainstem Neurons Controlling Rhythmic Activity

    PubMed Central

    Hull, Michael J.; Soffe, Stephen R.; Willshaw, David J.; Roberts, Alan

    2015-01-01

    Gap junctions between fine unmyelinated axons can electrically couple groups of brain neurons to synchronise firing and contribute to rhythmic activity. To explore the distribution and significance of electrical coupling, we modelled a well analysed, small population of brainstem neurons which drive swimming in young frog tadpoles. A passive network of 30 multicompartmental neurons with unmyelinated axons was used to infer that: axon-axon gap junctions close to the soma gave the best match to experimentally measured coupling coefficients; axon diameter had a strong influence on coupling; most neurons were coupled indirectly via the axons of other neurons. When active channels were added, gap junctions could make action potential propagation along the thin axons unreliable. Increased sodium and decreased potassium channel densities in the initial axon segment improved action potential propagation. Modelling suggested that the single spike firing to step current injection observed in whole-cell recordings is not a cellular property but a dynamic consequence of shunting resulting from electrical coupling. Without electrical coupling, firing of the population during depolarising current was unsynchronised; with coupling, the population showed synchronous recruitment and rhythmic firing. When activated instead by increasing levels of modelled sensory pathway input, the population without electrical coupling was recruited incrementally to unpatterned activity. However, when coupled, the population was recruited all-or-none at threshold into a rhythmic swimming pattern: the tadpole “decided” to swim. Modelling emphasises uncertainties about fine unmyelinated axon physiology but, when informed by biological data, makes general predictions about gap junctions: locations close to the soma; relatively small numbers; many indirect connections between neurons; cause of action potential propagation failure in fine axons; misleading alteration of intrinsic firing

  13. DOE Office of Scientific and Technical Information (OSTI.GOV)

    Miyawaki, Daisuke; Murakami, Masao; Demizu, Yusuke

    Purpose: To assess the incidence of early delayed or late morbidity of Brain after particle therapy for skull base tumors and head-and-neck cancers. Methods and Materials: Between May 2001 and December 2005, 59 patients with cancerous invasion of the skull base were treated with proton or carbon ion therapy at the Hyogo Ion Beam Medical Center. Adverse events were assessed according to the magnetic resonance imaging findings (late effects of normal tissue-subjective, objective, management, analytic [LENT-SOMA]) and symptoms (Common Terminology Criteria for Adverse Events [CTCAE], version 3.0). Dose-volume histograms were used to analyze the relationship between the dose and volumemore » of the irradiated brain and the occurrence of brain injury. The median follow-up time was 33 months. Results: Of the 48 patients treated with proton therapy and 11 patients treated with carbon ion radiotherapy, 8 (17%) and 7 (64%), respectively, developed radiation-induced brain changes (RIBCs) on magnetic resonance imaging (LENT-SOMA Grade 1-3). Four patients (7%) had some clinical symptoms, such as vertigo and headache (CTCAE Grade 2) or epilepsy (CTCAE Grade 3). The actuarial occurrence rate of RIBCs at 2 and 3 years was 20% and 39%, respectively, with a significant difference in the incidence between the proton and carbon ion radiotherapy groups. The dose-volume histogram analyses revealed significant differences between Brain lobes with and without RIBCs in the actuarial volume of brain lobes receiving high doses. Conclusion: Particle therapies produced minimal symptomatic brain toxicities, but sequential evaluation with magnetic resonance imaging detected a greater incidence of RIBCs. Significant differences were observed in the irradiated brain volume between Brain lobes with and without RIBCs.« less

  14. Zen and the brain: mutually illuminating topics

    PubMed Central

    Austin, James H.

    2013-01-01

    Zen Buddhist meditative practices emphasize the long-term, mindful training of attention and awareness during one's ordinary daily-life activities, the shedding of egocentric behaviors, and the skillful application of one's innate compassionate resources of insight-wisdom toward others and oneself. This review focuses on how such a comprehensive approach to training the brain could relate to a distinctive flavor of Zen: its emphasis on direct experience, with special reference to those major acute states of awakening that create deep transformations of consciousness and behavior. In Japanese, these advanced states are called kensho and satori. Ten key concepts are reviewed. They begin by distinguishing between the concentrative and receptive forms of meditation, noticing the complementary ways that they each train our normal “top–down” and “bottom–up” modes of attentive processing. Additional concepts distinguish between our two major processing pathways. The self-centered, egocentric frame of reference processes information in relation to our body (our soma) or to our mental functions (our psyche). The other-centered frame of reference processes information anonymously. Its prefix, allo- simply means “other” in Greek. Subsequent concepts consider how these useful Greek words—ego/allo, soma/psyche—correlate with the normal functional anatomy of important thalamo ↔ cortical connections. A plausible model then envisions how a triggering stimulus that captures attention could prompt the reticular nucleus to release GABA; how its selective inhibition of the dorsal thalamus could then block both our higher somatic and psychic cortical functions; so as to: (a) delete the maladaptive aspects of selfhood, while also (b) releasing the direct, all-inclusive, globally-unified experience of other. Two final concepts consider how the long-term meditative training of intuitive functions relates to certain kinds of word-free spatial tasks that involve

  15. The gonadotropin-inhibitory hormone (Lpxrfa) system's regulation of reproduction in the brain-pituitary axis of the zebrafish (Danio rerio).

    PubMed

    Spicer, Olivia Smith; Zmora, Nilli; Wong, Ten-Tsao; Golan, Matan; Levavi-Sivan, Berta; Gothilf, Yoav; Zohar, Yonathan

    2017-05-01

    Gonadotropin-inhibitory hormone (GNIH) was discovered in quail with the ability to reduce gonadotropin expression/secretion in the pituitary. There have been few studies on GNIH orthologs in teleosts (LPXRFamide (Lpxrfa) peptides), which have provided inconsistent results. Therefore, the goal of this study was to determine the roles and modes of action by which Lpxrfa exerts its functions in the brain-pituitary axis of zebrafish (Danio rerio). We localized Lpxrfa soma to the ventral hypothalamus, with fibers extending throughout the brain and to the pituitary. In the preoptic area, Lpxrfa fibers interact with gonadotropin-releasing hormone 3 (Gnrh3) soma. In pituitary explants, zebrafish peptide Lpxrfa-3 downregulated luteinizing hormone beta subunit and common alpha subunit expression. In addition, Lpxrfa-3 reduced gnrh3 expression in brain slices, offering another pathway for Lpxrfa to exert its effects on reproduction. Receptor activation studies, in a heterologous cell-based system, revealed that all three zebrafish Lpxrfa peptides activate Lpxrf-R2 and Lpxrf-R3 via the PKA/cAMP pathway. Receptor activation studies demonstrated that, in addition to activating Lpxrf receptors, zebrafish Lpxrfa-2 and Lpxrfa-3 antagonize Kisspeptin-2 (Kiss2) activation of Kisspeptin receptor-1a (Kiss1ra). The fact that kiss1ra-expressing neurons in the preoptic area are innervated by Lpxrfa-ir fibers suggests an additional pathway for Lpxrfa action. Therefore, our results suggest that Lpxrfa may act as a reproductive inhibitory neuropeptide in the zebrafish that interacts with Gnrh3 neurons in the brain and with gonadotropes in the pituitary, while also potentially utilizing the Kiss2/Kiss1ra pathway. © The Authors 2017. Published by Oxford University Press on behalf of Society for the Study of Reproduction. All rights reserved. For permissions, please e-mail: journals.permissions@oup.com.

  16. The Sociology of the Deceased Harvard Medical Unit at Boston City Hospital.

    PubMed

    Tishler, Peter V

    2015-12-01

    Many graduates of the Harvard Medical Unit (HMU) at Boston City Hospital, in either the clinical training/residency program or the research program at the Thorndike Memorial Laboratory, contributed in major ways to the HMU and constantly relived their HMU experiences. The HMU staff physicians, descending from founder and mentor physicians Francis W. Peabody, Soma Weiss, and George R. Minot, were dedicated to the teaching, development, and leadership of its clinical and research trainees, whose confidence and dedication to patient care as a result of their mentorship led many to lifelong achievements as clinicians, teachers, and mentors. Their experience also led to a lifelong love of the HMU (despite its loss), camaraderie, happiness, and intense friendships with their associates.

  17. Application of microtremor horizontal-to-vertical spectral ratio (MHVSR) analysis for site characterization: State of the art

    USGS Publications Warehouse

    Molnar, S.; Cassidy, J. F.; Castellaro, S.; Cornou, C.; Crow, H.; Hunter, J. A.; Matsushima, S.; Sanchez-Sesma, F. J.; Yong, Alan

    2018-01-01

    Nakamura (Q Rep Railway Tech Res Inst 30:25–33, 1989) popularized the application of the horizontal-to-vertical spectral ratio (HVSR) analysis of microtremor (seismic noise or ambient vibration) recordings to estimate the predominant frequency and amplification factor of earthquake shaking. During the following quarter century, popularity in the microtremor HVSR (MHVSR) method grew; studies have verified the stability of a site’s MHVSR response over time and validated the MHVSR response with that of earthquake HVSR response. Today, MHVSR analysis is a popular reconnaissance tool used worldwide for seismic microzonation and earthquake site characterization in numerous regions, specifically, in the mapping of site period or fundamental frequency and inverted for shear-wave velocity depth profiles, respectively. However, the ubiquity of MHVSR analysis is predominantly a consequence of its ease in application rather than our full understanding of its theory. We present the state of the art in MHVSR analyses in terms of the development of its theoretical basis, current state of practice, and we comment on its future for applications in earthquake site characterization.

  18. Chorein interacts with α-tubulin and histone deacetylase 6, and overexpression preserves cell viability during nutrient deprivation in human embryonic kidney 293 cells.

    PubMed

    Sasaki, Natsuki; Nakamura, Masayuki; Kodama, Akiko; Urata, Yuka; Shiokawa, Nari; Hayashi, Takehiro; Sano, Akira

    2016-11-01

    The autophagy pathway has recently been implicated in several neurodegenerative diseases. Recently, it was reported that chorein-depleted cells showed accumulation of autophagic markers and impaired autophagic flux. Here, we demonstrate that chorein overexpression preserves cell viability from starvation-induced cell death in human embryonic kidney 293 (HEK293) cells. Subsequent coimmunoprecipitation and reverse coimmunoprecipitation assays using extracts from chorein that stably overexpressed HEK293 cells revealed that chorein interacts with α-tubulin and histone deacetylase 6, a known α-tubulin deacetylater and central component of basal autophagy. Indeed, acetylated α-tubulin immunoreactivity was significantly decreased in chorein that stably overexpressed HEK293 cells. These results suggest that chorein/histone deacetylase 6/α-tubulin interactions may play an important role in starvation-induced cell stress, and their disruption may be one of the molecular pathogenic mechanisms of chorea-acanthocytosis.-Sasaki, N., Nakamura, M., Kodama, A., Urata, Y., Shiokawa, N., Hayashi, T., Sano, A. Chorein interacts with α-tubulin and histone deacetylase 6, and overexpression preserves cell viability during nutrient deprivation in human embryonic kidney 293 cells. © FASEB.

  19. Application of Microtremor Horizontal-to-Vertical Spectral Ratio (MHVSR) Analysis for Site Characterization: State of the Art

    NASA Astrophysics Data System (ADS)

    Molnar, S.; Cassidy, J. F.; Castellaro, S.; Cornou, C.; Crow, H.; Hunter, J. A.; Matsushima, S.; Sánchez-Sesma, F. J.; Yong, A.

    2018-03-01

    Nakamura (Q Rep Railway Tech Res Inst 30:25-33, 1989) popularized the application of the horizontal-to-vertical spectral ratio (HVSR) analysis of microtremor (seismic noise or ambient vibration) recordings to estimate the predominant frequency and amplification factor of earthquake shaking. During the following quarter century, popularity in the microtremor HVSR (MHVSR) method grew; studies have verified the stability of a site's MHVSR response over time and validated the MHVSR response with that of earthquake HVSR response. Today, MHVSR analysis is a popular reconnaissance tool used worldwide for seismic microzonation and earthquake site characterization in numerous regions, specifically, in the mapping of site period or fundamental frequency and inverted for shear-wave velocity depth profiles, respectively. However, the ubiquity of MHVSR analysis is predominantly a consequence of its ease in application rather than our full understanding of its theory. We present the state of the art in MHVSR analyses in terms of the development of its theoretical basis, current state of practice, and we comment on its future for applications in earthquake site characterization.

  20. Method of Electroporation for the Early Chick Embryo

    NASA Astrophysics Data System (ADS)

    Hatakeyama, Jun; Shimamura, Kenji

    Chick embryos have long been one of the favored model systems in the field of embryology and developmental biology. Recent advances in the gene manipulation technologies (Muramatsu et al., 1997; Nakamura et al., 2004) make this model system even more attractive for the developmental biologists (see review by Stern, 2005). Thanks to its two dimensional geometry, easiness in accessibility and observation, and well-established fate maps (e.g. Couly and Le Douarin, 1988; Garcia-Martinez et al., 1993; Hatada and Stern, 1994; Psychoyos and Stern, 1996; Sawada and Aoyama, 1999; Cobos et al., 2001; Lopez-Sanchez et al., 2001; Redkar et al., 2001; Fernandez-Garre et al., 2002; Kimura et al., 2006; Matsushita et al., 2008), it has great advantages especially for studies at the early embryonic stages, such as the processes of gastrulation, neural induction, left-right patterning, etc. For such purposes, a whole embryo culture system, originally invented by Dennis A. T. New (New, 1955), and its derivatives (Flamme, 1987; Sundin and Eichele, 1992; Stern, 1993; Chapman et al., 2001) have been widely used.

  1. Enzymatic analysis of a thermostabilized mutant of an Escherichia coli hygromycin B phosphotransferase.

    PubMed

    Nakamura, Akira; Takakura, Yasuaki; Sugimoto, Naohisa; Takaya, Naoki; Shiraki, Kentaro; Hoshino, Takayuki

    2008-09-01

    An Escherichia coli hygromycin B phosphotransferase (HPH) and its thermostabilized mutant protein, HPH5, containing five amino acid substitutions, D20G, A118V, S225P, Q226L, and T246A (Nakamura et al., J. Biosci. Bioeng., 100, 158-163 (2005)), obtained by an in vivo directed evolution procedure in Thermus thermophilus, were produced and purified from E. coli recombinants, and enzymatic comparisons were performed. The optimum temperatures for enzyme activity were 50 and 55 degrees C for HPH and HPH5 respectively, but the thermal stability of the enzyme activity and the temperature for protein denaturation of HPH5 increased, from 36 and 37.2 degrees C of HPH to 53 and 58.8 degrees C respectively. Specific activities and steady-state kinetics measured at 25 degrees C showed only slight differences between the two enzymes. From these results we concluded that HPH5 was thermostabilized at the protein level, and that the mutations introduced did not affect its enzyme activity, at least under the assay conditions.

  2. The worldwide Protein Data Bank (wwPDB): ensuring a single, uniform archive of PDB data

    PubMed Central

    Berman, Helen; Henrick, Kim; Nakamura, Haruki; Markley, John L.

    2007-01-01

    The worldwide Protein Data Bank (wwPDB) is the international collaboration that manages the deposition, processing and distribution of the PDB archive. The online PDB archive is a repository for the coordinates and related information for more than 38 000 structures, including proteins, nucleic acids and large macromolecular complexes that have been determined using X-ray crystallography, NMR and electron microscopy techniques. The founding members of the wwPDB are RCSB PDB (USA), MSD-EBI (Europe) and PDBj (Japan) [H.M. Berman, K. Henrick and H. Nakamura (2003) Nature Struct. Biol., 10, 980]. The BMRB group (USA) joined the wwPDB in 2006. The mission of the wwPDB is to maintain a single archive of macromolecular structural data that are freely and publicly available to the global community. Additionally, the wwPDB provides a variety of services to a broad community of users. The wwPDB website at provides information about services provided by the individual member organizations and about projects undertaken by the wwPDB. PMID:17142228

  3. Application of Microtremor Horizontal-to-Vertical Spectral Ratio (MHVSR) Analysis for Site Characterization: State of the Art

    NASA Astrophysics Data System (ADS)

    Molnar, S.; Cassidy, J. F.; Castellaro, S.; Cornou, C.; Crow, H.; Hunter, J. A.; Matsushima, S.; Sánchez-Sesma, F. J.; Yong, A.

    2018-07-01

    Nakamura (Q Rep Railway Tech Res Inst 30:25-33, 1989) popularized the application of the horizontal-to-vertical spectral ratio (HVSR) analysis of microtremor (seismic noise or ambient vibration) recordings to estimate the predominant frequency and amplification factor of earthquake shaking. During the following quarter century, popularity in the microtremor HVSR (MHVSR) method grew; studies have verified the stability of a site's MHVSR response over time and validated the MHVSR response with that of earthquake HVSR response. Today, MHVSR analysis is a popular reconnaissance tool used worldwide for seismic microzonation and earthquake site characterization in numerous regions, specifically, in the mapping of site period or fundamental frequency and inverted for shear-wave velocity depth profiles, respectively. However, the ubiquity of MHVSR analysis is predominantly a consequence of its ease in application rather than our full understanding of its theory. We present the state of the art in MHVSR analyses in terms of the development of its theoretical basis, current state of practice, and we comment on its future for applications in earthquake site characterization.

  4. Morphological Diversity of the Rod Spherule: A Study of Serially Reconstructed Electron Micrographs

    PubMed Central

    Li, Shuai; Mitchell, Joe; Briggs, Deidrie J.; Young, Jaime K.; Long, Samuel S.; Fuerst, Peter G.

    2016-01-01

    Purpose Rod spherules are the site of the first synaptic contact in the retina’s rod pathway, linking rods to horizontal and bipolar cells. Rod spherules have been described and characterized through electron micrograph (EM) and other studies, but their morphological diversity related to retinal circuitry and their intracellular structures have not been quantified. Most rod spherules are connected to their soma by an axon, but spherules of rods on the surface of the Mus musculus outer plexiform layer often lack an axon and have a spherule structure that is morphologically distinct from rod spherules connected to their soma by an axon. Retraction of the rod axon and spherule is often observed in disease processes and aging, and the retracted rod spherule superficially resembles rod spherules lacking an axon. We hypothesized that retracted spherules take on an axonless spherule morphology, which may be easier to maintain in a diseased state. To test our hypothesis, we quantified the spatial organization and subcellular structures of rod spherules with and without axons. We then compared them to the retracted spherules in a disease model, mice that overexpress Dscam (Down syndrome cell adhesion molecule), to gain a better understanding of the rod synapse in health and disease. Methods We reconstructed serial EM images of wild type and DscamGoF (gain of function) rod spherules at a resolution of 7 nm in the X-Y axis and 60 nm in the Z axis. Rod spherules with and without axons, and retracted spherules in the DscamGoF retina, were reconstructed. The rod spherule intracellular organelles, the invaginating dendrites of rod bipolar cells and horizontal cell axon tips were also reconstructed for statistical analysis. Results Stereotypical rod (R1) spherules occupy the outer two-thirds of the outer plexiform layer (OPL), where they present as spherical terminals with large mitochondria. This spherule group is highly uniform and composed more than 90% of the rod spherule

  5. Morphological Diversity of the Rod Spherule: A Study of Serially Reconstructed Electron Micrographs.

    PubMed

    Li, Shuai; Mitchell, Joe; Briggs, Deidrie J; Young, Jaime K; Long, Samuel S; Fuerst, Peter G

    2016-01-01

    Rod spherules are the site of the first synaptic contact in the retina's rod pathway, linking rods to horizontal and bipolar cells. Rod spherules have been described and characterized through electron micrograph (EM) and other studies, but their morphological diversity related to retinal circuitry and their intracellular structures have not been quantified. Most rod spherules are connected to their soma by an axon, but spherules of rods on the surface of the Mus musculus outer plexiform layer often lack an axon and have a spherule structure that is morphologically distinct from rod spherules connected to their soma by an axon. Retraction of the rod axon and spherule is often observed in disease processes and aging, and the retracted rod spherule superficially resembles rod spherules lacking an axon. We hypothesized that retracted spherules take on an axonless spherule morphology, which may be easier to maintain in a diseased state. To test our hypothesis, we quantified the spatial organization and subcellular structures of rod spherules with and without axons. We then compared them to the retracted spherules in a disease model, mice that overexpress Dscam (Down syndrome cell adhesion molecule), to gain a better understanding of the rod synapse in health and disease. We reconstructed serial EM images of wild type and DscamGoF (gain of function) rod spherules at a resolution of 7 nm in the X-Y axis and 60 nm in the Z axis. Rod spherules with and without axons, and retracted spherules in the DscamGoF retina, were reconstructed. The rod spherule intracellular organelles, the invaginating dendrites of rod bipolar cells and horizontal cell axon tips were also reconstructed for statistical analysis. Stereotypical rod (R1) spherules occupy the outer two-thirds of the outer plexiform layer (OPL), where they present as spherical terminals with large mitochondria. This spherule group is highly uniform and composed more than 90% of the rod spherule population. Rod spherules

  6. Comparison of calculated beta- and gamma-ray doses after the Fukushima accident with data from single-grain luminescence retrospective dosimetry of quartz inclusions in a brick sample

    PubMed Central

    Endo, Satoru; Fujii, Keisuke; Kajimoto, Tsuyoshi; Tanaka, Kenichi; Stepanenko, Valeriy; Kolyzhenkov, Timofey; Petukhov, Aleksey; Akhmedova, Umukusum; Bogacheva, Viktoriia

    2018-01-01

    Abstract To estimate the beta- and gamma-ray doses in a brick sample taken from Odaka, Minami-Soma City, Fukushima Prefecture, Japan, a Monte Carlo calculation was performed with Particle and Heavy Ion Transport code System (PHITS) code. The calculated results were compared with data obtained by single-grain retrospective luminescence dosimetry of quartz inclusions in the brick sample. The calculated result agreed well with the measured data. The dose increase measured at the brick surface was explained by the beta-ray contribution, and the slight slope in the dose profile deeper in the brick was due to the gamma-ray contribution. The skin dose was estimated from the calculated result as 164 mGy over 3 years at the sampling site. PMID:29385528

  7. Comparison of calculated beta- and gamma-ray doses after the Fukushima accident with data from single-grain luminescence retrospective dosimetry of quartz inclusions in a brick sample.

    PubMed

    Endo, Satoru; Fujii, Keisuke; Kajimoto, Tsuyoshi; Tanaka, Kenichi; Stepanenko, Valeriy; Kolyzhenkov, Timofey; Petukhov, Aleksey; Akhmedova, Umukusum; Bogacheva, Viktoriia

    2018-05-01

    To estimate the beta- and gamma-ray doses in a brick sample taken from Odaka, Minami-Soma City, Fukushima Prefecture, Japan, a Monte Carlo calculation was performed with Particle and Heavy Ion Transport code System (PHITS) code. The calculated results were compared with data obtained by single-grain retrospective luminescence dosimetry of quartz inclusions in the brick sample. The calculated result agreed well with the measured data. The dose increase measured at the brick surface was explained by the beta-ray contribution, and the slight slope in the dose profile deeper in the brick was due to the gamma-ray contribution. The skin dose was estimated from the calculated result as 164 mGy over 3 years at the sampling site.

  8. Bion's thinking about groups: a study of influence and originality.

    PubMed

    Schneider, John A

    2015-04-01

    One of Bion's least-acknowledged contributions to psychoanalytic theory is his study of the relationship between the mind of the individual (the ability to think), the mentalities of groups of which the individual is a member, and the individual's bodily states. Bion's early work on group therapy evolved into a study of the interplay between mind and bodily instincts associated with being a member of a group, and became the impetus for his theory of thinking. On the foundation of Bion's ideas concerning this interaction among the thinking of the individual, group mentality, and the psyche-soma, the author presents his thoughts on the ways in which group mentality is recognizable in the analysis of individuals. © 2015 The Psychoanalytic Quarterly, Inc.

  9. Simulation of Radiation Damage to Neural Cells with the Geant4-DNA Toolkit

    NASA Astrophysics Data System (ADS)

    Bayarchimeg, Lkhagvaa; Batmunkh, Munkhbaatar; Belov, Oleg; Lkhagva, Oidov

    2018-02-01

    To help in understanding the physical and biological mechanisms underlying effects of cosmic and therapeutic types of radiation on the central nervous system (CNS), we have developed an original neuron application based on the Geant4 Monte Carlo simulation toolkit, in particular on its biophysical extension Geant4-DNA. The applied simulation technique provides a tool for the simulation of physical, physico-chemical and chemical processes (e.g. production of water radiolysis species in the vicinity of neurons) in realistic geometrical model of neural cells exposed to ionizing radiation. The present study evaluates the microscopic energy depositions and water radiolysis species yields within a detailed structure of a selected neuron taking into account its soma, dendrites, axon and spines following irradiation with carbon and iron ions.

  10. Fourth revolution in psychiatry - Addressing comorbidity with chronic physical disorders.

    PubMed

    Gautam, Shiv

    2010-07-01

    The moral treatment of mental patients, Electro Convulsive therapy (ECT), and Psychotropic medications constitute the first, second, and third revolution in psychiatry, respectively. Addressing comorbidities of mental illnesses with chronic physical illnesses will be the fourth revolution in psychiatry. Mind and body are inseparable; there is a bidirectional relationship between psyche and soma, each influencing the other. Plausible biochemical explanations are appearing at an astonishing rate. Psychiatric comorbidity with many chronic physical disorders has remained neglected. Such comorbidity with cardiac, respiratory, Gastrointestinal, endocrinal, and neurological disorders, trauma, and other conditions like HIV and so on, needs to be addressed too. Evidence base of prevalence and causal relationship of psychiatric comorbidities in these disorders has been highlighted and strategies to meet the challenge of comorbidity have been indicated.

  11. Case study: Optimizing fault model input parameters using bio-inspired algorithms

    NASA Astrophysics Data System (ADS)

    Plucar, Jan; Grunt, Onřej; Zelinka, Ivan

    2017-07-01

    We present a case study that demonstrates a bio-inspired approach in the process of finding optimal parameters for GSM fault model. This model is constructed using Petri Nets approach it represents dynamic model of GSM network environment in the suburban areas of Ostrava city (Czech Republic). We have been faced with a task of finding optimal parameters for an application that requires high amount of data transfers between the application itself and secure servers located in datacenter. In order to find the optimal set of parameters we employ bio-inspired algorithms such as Differential Evolution (DE) or Self Organizing Migrating Algorithm (SOMA). In this paper we present use of these algorithms, compare results and judge their performance in fault probability mitigation.

  12. The Sociology of the Deceased Harvard Medical Unit at Boston City Hospital

    PubMed Central

    Tishler, Peter V.

    2015-01-01

    Many graduates of the Harvard Medical Unit (HMU) at Boston City Hospital, in either the clinical training/residency program or the research program at the Thorndike Memorial Laboratory, contributed in major ways to the HMU and constantly relived their HMU experiences. The HMU staff physicians, descending from founder and mentor physicians Francis W. Peabody, Soma Weiss, and George R. Minot, were dedicated to the teaching, development, and leadership of its clinical and research trainees, whose confidence and dedication to patient care as a result of their mentorship led many to lifelong achievements as clinicians, teachers, and mentors. Their experience also led to a lifelong love of the HMU (despite its loss), camaraderie, happiness, and intense friendships with their associates. PMID:26604868

  13. NeuroTessMesh: A Tool for the Generation and Visualization of Neuron Meshes and Adaptive On-the-Fly Refinement.

    PubMed

    Garcia-Cantero, Juan J; Brito, Juan P; Mata, Susana; Bayona, Sofia; Pastor, Luis

    2017-01-01

    Gaining a better understanding of the human brain continues to be one of the greatest challenges for science, largely because of the overwhelming complexity of the brain and the difficulty of analyzing the features and behavior of dense neural networks. Regarding analysis, 3D visualization has proven to be a useful tool for the evaluation of complex systems. However, the large number of neurons in non-trivial circuits, together with their intricate geometry, makes the visualization of a neuronal scenario an extremely challenging computational problem. Previous work in this area dealt with the generation of 3D polygonal meshes that approximated the cells' overall anatomy but did not attempt to deal with the extremely high storage and computational cost required to manage a complex scene. This paper presents NeuroTessMesh, a tool specifically designed to cope with many of the problems associated with the visualization of neural circuits that are comprised of large numbers of cells. In addition, this method facilitates the recovery and visualization of the 3D geometry of cells included in databases, such as NeuroMorpho, and provides the tools needed to approximate missing information such as the soma's morphology. This method takes as its only input the available compact, yet incomplete, morphological tracings of the cells as acquired by neuroscientists. It uses a multiresolution approach that combines an initial, coarse mesh generation with subsequent on-the-fly adaptive mesh refinement stages using tessellation shaders. For the coarse mesh generation, a novel approach, based on the Finite Element Method, allows approximation of the 3D shape of the soma from its incomplete description. Subsequently, the adaptive refinement process performed in the graphic card generates meshes that provide good visual quality geometries at a reasonable computational cost, both in terms of memory and rendering time. All the described techniques have been integrated into Neuro

  14. Macronuclear Genome Sequence of the Ciliate Tetrahymena thermophila, a Model Eukaryote

    PubMed Central

    Eisen, Jonathan A; Coyne, Robert S; Wu, Martin; Wu, Dongying; Thiagarajan, Mathangi; Wortman, Jennifer R; Badger, Jonathan H; Ren, Qinghu; Amedeo, Paolo; Jones, Kristie M; Tallon, Luke J; Delcher, Arthur L; Salzberg, Steven L; Silva, Joana C; Haas, Brian J; Majoros, William H; Farzad, Maryam; Carlton, Jane M; Smith, Roger K; Garg, Jyoti; Pearlman, Ronald E; Karrer, Kathleen M; Sun, Lei; Manning, Gerard; Elde, Nels C; Turkewitz, Aaron P; Asai, David J; Wilkes, David E; Wang, Yufeng; Cai, Hong; Collins, Kathleen; Stewart, B. Andrew; Lee, Suzanne R; Wilamowska, Katarzyna; Weinberg, Zasha; Ruzzo, Walter L; Wloga, Dorota; Gaertig, Jacek; Frankel, Joseph; Tsao, Che-Chia; Gorovsky, Martin A; Keeling, Patrick J; Waller, Ross F; Patron, Nicola J; Cherry, J. Michael; Stover, Nicholas A; Krieger, Cynthia J; del Toro, Christina; Ryder, Hilary F; Williamson, Sondra C; Barbeau, Rebecca A; Hamilton, Eileen P; Orias, Eduardo

    2006-01-01

    The ciliate Tetrahymena thermophila is a model organism for molecular and cellular biology. Like other ciliates, this species has separate germline and soma functions that are embodied by distinct nuclei within a single cell. The germline-like micronucleus (MIC) has its genome held in reserve for sexual reproduction. The soma-like macronucleus (MAC), which possesses a genome processed from that of the MIC, is the center of gene expression and does not directly contribute DNA to sexual progeny. We report here the shotgun sequencing, assembly, and analysis of the MAC genome of T. thermophila, which is approximately 104 Mb in length and composed of approximately 225 chromosomes. Overall, the gene set is robust, with more than 27,000 predicted protein-coding genes, 15,000 of which have strong matches to genes in other organisms. The functional diversity encoded by these genes is substantial and reflects the complexity of processes required for a free-living, predatory, single-celled organism. This is highlighted by the abundance of lineage-specific duplications of genes with predicted roles in sensing and responding to environmental conditions (e.g., kinases), using diverse resources (e.g., proteases and transporters), and generating structural complexity (e.g., kinesins and dyneins). In contrast to the other lineages of alveolates (apicomplexans and dinoflagellates), no compelling evidence could be found for plastid-derived genes in the genome. UGA, the only T. thermophila stop codon, is used in some genes to encode selenocysteine, thus making this organism the first known with the potential to translate all 64 codons in nuclear genes into amino acids. We present genomic evidence supporting the hypothesis that the excision of DNA from the MIC to generate the MAC specifically targets foreign DNA as a form of genome self-defense. The combination of the genome sequence, the functional diversity encoded therein, and the presence of some pathways missing from other model

  15. Does cochlear implantation and electrical stimulation affect residual hair cells and spiral ganglion neurons?

    PubMed Central

    Coco, Anne; Epp, Stephanie B.; Fallon, James B.; Xu, Jin; Millard, Rodney E.; Shepherd, Robert K.

    2007-01-01

    Increasing numbers of cochlear implant subjects have some level of residual hearing at the time of implantation. The present study examined whether (i) hair cells that have survived one pathological insult (aminoglycoside deafening), can survive and function following long-term cochlear implantation and electrical stimulation (ES); and (ii) chronic ES in these cochleae results in greater trophic support of spiral ganglion neurons (SGNs) compared with cochleae devoid of hair cells. Eight cats, with either partial (n=4) or severe (n=4) sensorineural hearing loss, were bilaterally implanted with scala tympani electrode arrays 2 months after deafening, and received unilateral ES using charge balanced biphasic current pulses for periods of up to 235 days. Frequency-specific compound action potentials and click-evoked auditory brainstem responses (ABRs) were recorded periodically to monitor the residual acoustic hearing. Electrically-evoked ABRs (EABRs) were recorded to confirm the stimulus levels were 3-6 dB above the EABR threshold. On completion of the ES program the cochleae were examined histologically. Partially deafened animals showed no significant increase in acoustic thresholds over the implantation period. Moreover, chronic ES of an electrode array located in the base of the cochlea did not adversely affect hair cells in the middle or apical turns. There was evidence of a small but statistically significant rescue of SGNs in the middle and apical turns of stimulated cochleae in animals with partial hearing. Chronic ES did not, however, prevent a reduction in SGN density for the severely deaf cohort, although SGNs adjacent to the stimulating electrodes did exhibit a significant increase in soma area (p<0.01). In sum, chronic ES in partial hearing animals does not adversely affect functioning residual hair cells apical to the electrode array. Moreover, while there is an increase in the soma area of SGNs close to the stimulating electrodes in severely deaf

  16. Cytoplasmic segregation and cytoskeletal organization in the electric catfish giant electromotoneuron with special reference to the axon hillock region.

    PubMed

    Braun, N; Schikorski, T; Zimmermann, H

    1993-02-01

    The cytoplasm of the highly polarized nerve cell is permanently segregated into domains with differing organellar composition. The mechanisms maintaining this segregation are largely unknown. In order to elucidate the potential role of cytoskeletal elements in this process we compared the cytoplasmic segregation within the giant electromotoneuron of the electric catfish (Malapterurus electricus) with the distribution of binding sites for antibodies against elements of the cytoskeleton. Most prominent cytoplasmic segregations include the formation of a subplasmalemmal cortical structure free of Nissl bodies and Golgi cisternae, the separation within the soma of domains containing rough endoplasmic reticulum and filament-rich domains, and the soma-axon transition. The cytoplasmic transition at the axon hillock forms a distinct borderline where Nissl bodies, Golgi cisternae and the bulk of lysosomes abruptly terminate and are excluded from the axoplasm. Synaptic vesicles and mitochondria are free to pass compartmental borders. Tropomyosin, spectrin, and alpha-actinin reveal a rather homogeneous immunofluorescence throughout the neuron. In contrast, neurofilament protein and tubulin display a distinctly increased immunofluorescence in the subplasmalemmal cortical layer, in dendrites as well as in the axon. The increase in immunofluorescence at the axon hillock exactly depicts the small transition zone from the somatic cytoplasm rich in Nissl bodies, Golgi cisternae and lysosomes to the differently structured axoplasm. The picture is similar for beta-tubulin, tyrosinylated and detyrosinylated alpha-tubulin. Detyrosinylated tubulin (glu-tubulin, which is contained in microtubules of increased stability) shows the most prominent enrichment in the axon. The distribution of myosin is comparable to that of neurofilament protein but there is less difference in immunofluorescence between the domains. Our results would be compatible with a role of microtubules together with

  17. Developmental Programming: Reproductive Endocrinopathies in the Adult Female Sheep After Prenatal Testosterone Treatment Are Reflected in Altered Ontogeny of GnRH Afferents

    PubMed Central

    Hershey, John; Mytinger, Andrea; Foster, Douglas L.; Padmanabhan, Vasantha

    2011-01-01

    The GnRH system represents a useful model of long-term neural plasticity. An unexplored facet of this plasticity relates to the ontogeny of GnRH neural afferents during critical periods when the hypothalamic-pituitary-gonadal axis is highly susceptible to perturbation by sex steroids. Sheep treated with testosterone (T) in utero exhibit profound reproductive neuroendocrine dysfunctions during their lifespan. The current study tested the hypothesis that these changes are associated with alterations in the normal ontogeny of GnRH afferents and glial associations. Adult pregnant sheep (n = 50) were treated with vehicle [control (CONT)] or T daily from gestational day (GD)30 to GD90. CONT and T fetuses (n = 4–6/treatment per age group) were removed by cesarean section on GD90 and GD140 and the brains frozen at −80°C. Brains were also collected from CONT and T females at 20–23 wk (prepubertal), 10 months (normal onset of puberty and oligo-anovulation), and 21 months (oligo-anovulation in T females). Tissue was analyzed for GnRH immunoreactivity (ir), total GnRH afferents (Synapsin-I ir), glutamate [vesicular glutamate transporter-2 (VGLUT2)-ir], and γ-aminobutyric acid [GABA, vesicular GABA transporter (VGAT)-ir] afferents and glial associations (glial fibrillary acidic protein-ir) with GnRH neurons using optical sectioning techniques. The results revealed that: 1) GnRH soma size was slightly reduced by T, 2) the total (Synapsin-I) GnRH afferents onto both somas and dendrites increased significantly with age and was reduced by T, 3) numbers of both VGAT and VGLUT inputs increased significantly with age and were also reduced by T, and 4) glial associations with GnRH neurons were reduced (<10%) by T. Together, these findings reveal a previously unknown developmental plasticity in the GnRH system of the sheep. The altered developmental trajectory of GnRH afferents after T reinforces the notion that prenatal programming plays an important role in the normal

  18. Calcium buffering properties of calbindin D28k and parvalbumin in rat sensory neurones.

    PubMed Central

    Chard, P S; Bleakman, D; Christakos, S; Fullmer, C S; Miller, R J

    1993-01-01

    1. We have examined the ability of the Ca(2+)-binding proteins (CABP) calbindin D28k and paravalbumin to modulate increases in the intracellular free Ca2+ concentration ([Ca2+]i), produced by brief depolarizations, in rat dorsal root ganglion (DRG) neurones. 2. In order to obtain good voltage control, we replated DRG neurones prior to performing these experiments. Immunocytochemical staining of these cells revealed that approximately 10% stained for CABPs. 3. Using fluorescently labelled parvalbumin, we demonstrated that in the whole-cell voltage clamp mode the protein freely entered the cell soma with a mean half-life t0.5 of 6 min 22 s +/- 54 s. 4. Analysis of the effects of calbindin D28k (370 microM) and parvalbumin (1 mM) on Ca2+ currents in the whole-cell voltage clamp mode, revealed that neither protein changed the rate of inactivation of the Ca2+ current or its rate of run-down. 5. Introducing either calbindin D28k (370 microM) or parvalbumin (1 mM) into the cell soma did not significantly alter the basal [Ca2+]i when compared to control cells. 6. Compared to control cells, both CABPs significantly reduced the peak [Ca2+]i obtained for a Ca2+ influx of an equivalent charge density, whereas lysozyme (1 mM), a protein with low affinity for Ca2+, failed to do so. 7. Calbindin D28k caused an 8-fold decrease in the rate of rise in [Ca2+]i and altered the kinetics of decay of [Ca2+]i to a single slow component. Parvalbumin also slowed the rate of rise in [Ca2+]i. Parvalbumin selectively increased a fast component in the decay of the Ca2+ signal. 8. These data demonstrate that both calbindin D28k and paravalbumin effectively buffer Ca2+ in a cellular environment and may therefore regulate Ca(2+)-dependent aspects of neuronal function. Images Fig. 1 PMID:8145149

  19. Mycolactone-mediated neurite degeneration and functional effects in cultured human and rat DRG neurons

    PubMed Central

    Sinisi, M; Fox, M; MacQuillan, A; Quick, T; Korchev, Y; Bountra, C; McCarthy, T; Anand, P

    2016-01-01

    Background Mycolactone is a polyketide toxin secreted by the mycobacterium Mycobacterium ulcerans, responsible for the extensive hypoalgesic skin lesions characteristic of patients with Buruli ulcer. A recent pre-clinical study proposed that mycolactone may produce analgesia via activation of the angiotensin II type 2 receptor (AT2R). In contrast, AT2R antagonist EMA401 has shown analgesic efficacy in animal models and clinical trials for neuropathic pain. We therefore investigated the morphological and functional effects of mycolactone in cultured human and rat dorsal root ganglia (DRG) neurons and the role of AT2R using EMA401. Primary sensory neurons were prepared from avulsed cervical human DRG and rat DRG; 24 h after plating, neurons were incubated for 24 to 96 h with synthetic mycolactone A/B, followed by immunostaining with antibodies to PGP9.5, Gap43, β tubulin, or Mitotracker dye staining. Acute functional effects were examined by measuring capsaicin responses with calcium imaging in DRG neuronal cultures treated with mycolactone. Results Morphological effects: Mycolactone-treated cultures showed dramatically reduced numbers of surviving neurons and non-neuronal cells, reduced Gap43 and β tubulin expression, degenerating neurites and reduced cell body diameter, compared with controls. Dose-related reduction of neurite length was observed in mycolactone-treated cultures. Mitochondria were distributed throughout the length of neurites and soma of control neurons, but clustered in the neurites and soma of mycolactone-treated neurons. Functional effects: Mycolactone-treated human and rat DRG neurons showed dose-related inhibition of capsaicin responses, which were reversed by calcineurin inhibitor cyclosporine and phosphodiesterase inhibitor 3-isobutyl-1-Methylxanthine, indicating involvement of cAMP/ATP reduction. The morphological and functional effects of mycolactone were not altered by Angiotensin II or AT2R antagonist EMA401. Conclusion Mycolactone

  20. Mycolactone-mediated neurite degeneration and functional effects in cultured human and rat DRG neurons: Mechanisms underlying hypoalgesia in Buruli ulcer.

    PubMed

    Anand, U; Sinisi, M; Fox, M; MacQuillan, A; Quick, T; Korchev, Y; Bountra, C; McCarthy, T; Anand, P

    2016-01-01

    Mycolactone is a polyketide toxin secreted by the mycobacterium Mycobacterium ulcerans, responsible for the extensive hypoalgesic skin lesions characteristic of patients with Buruli ulcer. A recent pre-clinical study proposed that mycolactone may produce analgesia via activation of the angiotensin II type 2 receptor (AT2R). In contrast, AT2R antagonist EMA401 has shown analgesic efficacy in animal models and clinical trials for neuropathic pain. We therefore investigated the morphological and functional effects of mycolactone in cultured human and rat dorsal root ganglia (DRG) neurons and the role of AT2R using EMA401. Primary sensory neurons were prepared from avulsed cervical human DRG and rat DRG; 24 h after plating, neurons were incubated for 24 to 96 h with synthetic mycolactone A/B, followed by immunostaining with antibodies to PGP9.5, Gap43, β tubulin, or Mitotracker dye staining. Acute functional effects were examined by measuring capsaicin responses with calcium imaging in DRG neuronal cultures treated with mycolactone. Morphological effects: Mycolactone-treated cultures showed dramatically reduced numbers of surviving neurons and non-neuronal cells, reduced Gap43 and β tubulin expression, degenerating neurites and reduced cell body diameter, compared with controls. Dose-related reduction of neurite length was observed in mycolactone-treated cultures. Mitochondria were distributed throughout the length of neurites and soma of control neurons, but clustered in the neurites and soma of mycolactone-treated neurons. Functional effects: Mycolactone-treated human and rat DRG neurons showed dose-related inhibition of capsaicin responses, which were reversed by calcineurin inhibitor cyclosporine and phosphodiesterase inhibitor 3-isobutyl-1-Methylxanthine, indicating involvement of cAMP/ATP reduction. The morphological and functional effects of mycolactone were not altered by Angiotensin II or AT2R antagonist EMA401. Mycolactone induces toxic effects in DRG

  1. Layer 6 cortical neurons require Reelin-Dab1 signaling for cellular orientation, Golgi deployment, and directed neurite growth into the marginal zone.

    PubMed

    O'Dell, Ryan S; Ustine, Candida J M; Cameron, David A; Lawless, Sean M; Williams, Rebecca M; Zipfel, Warren R; Olson, Eric C

    2012-07-07

    The secreted ligand Reelin is believed to regulate the translocation of prospective layer 6 (L6) neocortical neurons into the preplate, a loose layer of pioneer neurons that overlies the ventricular zone. Recent studies have also suggested that Reelin controls neuronal orientation and polarized dendritic growth during this period of early cortical development. To explicitly characterize and quantify how Reelin controls this critical aspect of neurite initiation and growth we used a new ex utero explant model of early cortical development to selectively label a subset of L6 cortical neurons for complete 3-D reconstruction. The total neurite arbor sizes of neurons in Reelin-deficient (reeler mutant) and Dab1-deficient (Reelin-non-responsive scrambler mutant) cortices were quantified and unexpectedly were not different than control arbor lengths (p = 0.51). For each mutant, however, arbor organization was markedly different: mutant neurons manifested more primary processes (neurites emitted directly from the soma) than wild type, and these neurites were longer and displayed less branching. Reeler and scrambler mutant neurites extended tangentially rather than radially, and the Golgi apparatus that normally invests the apical neurite was compact in both reeler and scrambler mutants. Mutant cortices also exhibited a neurite "exclusion zone" which was relatively devoid of L6 neuron neurites and extended at least 15 μm beneath the pial surface, an area corresponding to the marginal zone (MZ) in the wild type explants. The presence of an exclusion zone was also indicated in the orientation of mutant primary neurite and neuronal somata, which failed to adopt angles within ~20˚ of the radial line to the pial surface. Injection of recombinant Reelin to reeler, but not scrambler, mutant cortices fully rescued soma orientation, Golgi organization, and dendritic projection defects within four hrs. These findings indicate Reelin promotes directional dendritic growth into

  2. Plants do not count… or do they? New perspectives on the universality of senescence

    PubMed Central

    Salguero-Gómez, Roberto; Shefferson, Richard P; Hutchings, Michael J

    2013-01-01

    1. Senescence, the physiological decline that results in decreasing survival and/or reproduction with age, remains one of the most perplexing topics in biology. Most theories explaining the evolution of senescence (i.e. antagonistic pleiotropy, accumulation of mutations, disposable soma) were developed decades ago. Even though these theories have implicitly focused on unitary animals, they have also been used as the foundation from which the universality of senescence across the tree of life is assumed. 2. Surprisingly, little is known about the general patterns, causes and consequences of whole-individual senescence in the plant kingdom. There are important differences between plants and most animals, including modular architecture, the absence of early determination of cell lines between the soma and gametes, and cellular division that does not always shorten telomere length. These characteristics violate the basic assumptions of the classical theories of senescence and therefore call the generality of senescence theories into question. 3. This Special Feature contributes to the field of whole-individual plant senescence with five research articles addressing topics ranging from physiology to demographic modelling and comparative analyses. These articles critically examine the basic assumptions of senescence theories such as age-specific gene action, the evolution of senescence regardless of the organism's architecture and environmental filtering, and the role of abiotic agents on mortality trajectories. 4. Synthesis. Understanding the conditions under which senescence has evolved is of general importance across biology, ecology, evolution, conservation biology, medicine, gerontology, law and social sciences. The question ‘why is senescence universal or why is it not?’ naturally calls for an evolutionary perspective. Senescence is a puzzling phenomenon, and new insights will be gained by uniting methods, theories and observations from formal demography

  3. mRNA for the EAAC1 Subtype of Glutamate Transporter is Present in Neuronal Dendrites In Vitro and Dramatically Increases In Vivo After a Seizure

    PubMed Central

    Ross, John R.; Porter, Brenda E.; Buckley, Peter T.; Eberwine, James H.; Robinson, Michael B.

    2011-01-01

    The neuronal Na+-dependent glutamate transporter, excitatory amino acid carrier 1 (EAAC1, also called EAAT3), has been implicated in the control of synaptic spillover of glutamate, synaptic plasticity, and the import of cysteine for neuronal synthesis of glutathione. EAAC1 protein is observed in both perisynaptic regions of the synapse and in neuronal cell bodies. Although amino acid residues in the carboxyl terminal tail have been implicated in the dendritic targeting of EAAC1 protein, it is not known if mRNA for EAAC1 may also be targeted to dendrites. Sorting of mRNA to specific cellular domains provides a mechanism by which signals can rapidly increase translation in a local environment; this form of regulated translation has been linked to diverse biological phenomena ranging from establishment of polarity during embryogenesis to synapse development and synaptic plasticity. In the present study, EAAC1 mRNA sequences were amplified from dendritic samples that were mechanically harvested from low-density hippocampal neuronal cultures. In parallel analyses, mRNA for histone deacetylase 2 (HDAC-2) and glial fibrillary acidic protein (GFAP) was not detected, suggesting that these samples are not contaminated with cell body or glial mRNAs. EAAC1 mRNA also co-localized with Map2a (a marker of dendrites) but not Tau1 (a marker of axons) in hippocampal neuronal cultures by in situ hybridization. In control rats, EAAC1 mRNA was observed in soma and proximal dendrites of hippocampal pyramidal neurons. Following pilocarpine- or kainate-induced seizures, EAAC1 mRNA was present in CA1 pyramidal cell dendrites up to 200 μm from the soma. These studies provide the first evidence that EAAC1 mRNA localizes to dendrites and suggest that dendritic targeting of EAAC1 mRNA is increased by seizure activity and may be regulated by neuronal activity/depolarization. PMID:21185901

  4. Evidence that GABA ρ subunits contribute to functional ionotropic GABA receptors in mouse cerebellar Purkinje cells

    PubMed Central

    Harvey, Victoria L; Duguid, Ian C; Krasel, Cornelius; Stephens, Gary J

    2006-01-01

    Ionotropic γ-amino butyric acid (GABA) receptors composed of heterogeneous molecular subunits are major mediators of inhibitory responses in the adult CNS. Here, we describe a novel ionotropic GABA receptor in mouse cerebellar Purkinje cells (PCs) using agents reported to have increased affinity for ρ subunit-containing GABAC over other GABA receptors. Exogenous application of the GABAC-preferring agonist cis-4-aminocrotonic acid (CACA) evoked whole-cell currents in PCs, whilst equimolar concentrations of GABA evoked larger currents. CACA-evoked currents had a greater sensitivity to the selective GABAC antagonist (1,2,5,6-tetrahydropyridin-4-yl)methylphosphinic acid (TPMPA) than GABA-evoked currents. Focal application of agonists produced a differential response profile; CACA-evoked currents displayed a much more pronounced attenuation with increasing distance from the PC soma, displayed a slower time-to-peak and exhibited less desensitization than GABA-evoked currents. However, CACA-evoked currents were also completely blocked by bicuculline, a selective agent for GABAA receptors. Thus, we describe a population of ionotropic GABA receptors with a mixed GABAA/GABAC pharmacology. TPMPA reduced inhibitory synaptic transmission at interneurone–Purkinje cell (IN–PC) synapses, causing clear reductions in miniature inhibitory postsynaptic current (mIPSC) amplitude and frequency. Combined application of NO-711 (a selective GABA transporter subtype 1 (GAT-1) antagonist) and SNAP-5114 (a GAT-(2)/3/4 antagonist) induced a tonic GABA conductance in PCs; however, TPMPA had no effect on this current. Immunohistochemical studies suggest that ρ subunits are expressed predominantly in PC soma and proximal dendritic compartments with a lower level of expression in more distal dendrites; this selective immunoreactivity contrasted with a more uniform distribution of GABAA α1 subunits in PCs. Finally, co-immunoprecipitation studies suggest that ρ subunits can form complexes

  5. A European Research Agenda for Somatic Symptom Disorders, Bodily Distress Disorders, and Functional Disorders: Results of an Estimate-Talk-Estimate Delphi Expert Study.

    PubMed

    van der Feltz-Cornelis, Christina M; Elfeddali, Iman; Werneke, Ursula; Malt, Ulrik F; Van den Bergh, Omer; Schaefert, Rainer; Kop, Willem J; Lobo, Antonio; Sharpe, Michael; Söllner, Wolfgang; Löwe, Bernd

    2018-01-01

    Background: Somatic Symptom Disorders (SSD), Bodily Distress Disorders (BDD) and functional disorders (FD) are associated with high medical and societal costs and pose a substantial challenge to the population and health policy of Europe. To meet this challenge, a specific research agenda is needed as one of the cornerstones of sustainable mental health research and health policy for SSD, BDD, and FD in Europe. Aim: To identify the main challenges and research priorities concerning SSD, BDD, and FD from a European perspective. Methods: Delphi study conducted from July 2016 until October 2017 in 3 rounds with 3 workshop meetings and 3 online surveys, involving 75 experts and 21 European countries. EURONET-SOMA and the European Association of Psychosomatic Medicine (EAPM) hosted the meetings. Results: Eight research priorities were identified: (1) Assessment of diagnostic profiles relevant to course and treatment outcome. (2) Development and evaluation of new, effective interventions. (3) Validation studies on questionnaires or semi-structured interviews that assess chronic medical conditions in this context. (4) Research into patients preferences for diagnosis and treatment. (5) Development of new methodologic designs to identify and explore mediators and moderators of clinical course and treatment outcomes (6). Translational research exploring how psychological and somatic symptoms develop from somatic conditions and biological and behavioral pathogenic factors. (7) Development of new, effective interventions to personalize treatment. (8) Implementation studies of treatment interventions in different settings, such as primary care, occupational care, general hospital and specialty mental health settings. The general public and policymakers will benefit from the development of new, effective, personalized interventions for SSD, BDD, and FD, that will be enhanced by translational research, as well as from the outcomes of research into patient involvement, GP

  6. Maintenance of neuronal size gradient in MNTB requires sound-evoked activity.

    PubMed

    Weatherstone, Jessica H; Kopp-Scheinpflug, Conny; Pilati, Nadia; Wang, Yuan; Forsythe, Ian D; Rubel, Edwin W; Tempel, Bruce L

    2017-02-01

    The medial nucleus of the trapezoid body (MNTB) is an important source of inhibition during the computation of sound location. It transmits fast and precisely timed action potentials at high frequencies; this requires an efficient calcium clearance mechanism, in which plasma membrane calcium ATPase 2 (PMCA2) is a key component. Deafwaddler ( dfw 2J ) mutant mice have a null mutation in PMCA2 causing deafness in homozygotes ( dfw 2J / dfw 2J ) and high-frequency hearing loss in heterozygotes (+/ dfw 2J ). Despite the deafness phenotype, no significant differences in MNTB volume or cell number were observed in dfw 2J homozygous mutants, suggesting that PMCA2 is not required for MNTB neuron survival. The MNTB tonotopic axis encodes high to low sound frequencies across the medial to lateral dimension. We discovered a cell size gradient along this axis: lateral neuronal somata are significantly larger than medially located somata. This size gradient is decreased in +/ dfw 2J and absent in dfw 2J / dfw 2J The lack of acoustically driven input suggests that sound-evoked activity is required for maintenance of the cell size gradient. This hypothesis was corroborated by selective elimination of auditory hair cell activity with either hair cell elimination in Pou4f3 DTR mice or inner ear tetrodotoxin (TTX) treatment. The change in soma size was reversible and recovered within 7 days of TTX treatment, suggesting that regulation of the gradient is dependent on synaptic activity and that these changes are plastic rather than permanent. NEW & NOTEWORTHY Neurons of the medial nucleus of the trapezoid body (MNTB) act as fast-spiking inhibitory interneurons within the auditory brain stem. The MNTB is topographically organized, with low sound frequencies encoded laterally and high frequencies medially. We discovered a cell size gradient along this axis: lateral neurons are larger than medial neurons. The absence of this gradient in deaf mice lacking plasma membrane calcium ATPase 2

  7. Comparative genome and transcriptome analyses of the social amoeba Acytostelium subglobosum that accomplishes multicellular development without germ-soma differentiation.

    PubMed

    Urushihara, Hideko; Kuwayama, Hidekazu; Fukuhara, Kensuke; Itoh, Takehiko; Kagoshima, Hiroshi; Shin-I, Tadasu; Toyoda, Atsushi; Ohishi, Kazuyo; Taniguchi, Tateaki; Noguchi, Hideki; Kuroki, Yoko; Hata, Takashi; Uchi, Kyoko; Mohri, Kurato; King, Jason S; Insall, Robert H; Kohara, Yuji; Fujiyama, Asao

    2015-02-14

    Social amoebae are lower eukaryotes that inhabit the soil. They are characterized by the construction of a starvation-induced multicellular fruiting body with a spore ball and supportive stalk. In most species, the stalk is filled with motile stalk cells, as represented by the model organism Dictyostelium discoideum, whose developmental mechanisms have been well characterized. However, in the genus Acytostelium, the stalk is acellular and all aggregated cells become spores. Phylogenetic analyses have shown that it is not an ancestral genus but has lost the ability to undergo cell differentiation. We performed genome and transcriptome analyses of Acytostelium subglobosum and compared our findings to other available dictyostelid genome data. Although A. subglobosum adopts a qualitatively different developmental program from other dictyostelids, its gene repertoire was largely conserved. Yet, families of polyketide synthase and extracellular matrix proteins have not expanded and a serine protease and ABC transporter B family gene, tagA, and a few other developmental genes are missing in the A. subglobosum lineage. Temporal gene expression patterns are astonishingly dissimilar from those of D. discoideum, and only a limited fraction of the ortholog pairs shared the same expression patterns, so that some signaling cascades for development seem to be disabled in A. subglobosum. The absence of the ability to undergo cell differentiation in Acytostelium is accompanied by a small change in coding potential and extensive alterations in gene expression patterns.

  8. NTS-polyplex: A potential nanocarrier for neurotrophic therapy of Parkinson’s disease

    PubMed Central

    Martinez-Fong, Daniel; Bannon, Michael J.; Trudeau, Louis-Eric; Gonzalez-Barrios, Juan A.; Arango-Rodriguez, Martha L.; Hernandez-Chan, Nancy G.; Reyes-Corona, David; Armendáriz-Borunda, Juan; Navarro-Quiroga, Ivan

    2012-01-01

    Nanomedicine has focused on targeted neurotrophic gene delivery to the brain as a strategy to stop and reverse neurodegeneration in Parkinson’s disease. Because of improved transfection ability, synthetic nanocarriers have become candidates for neurotrophic therapy. Neurotensin (NTS)-polyplex is a “Trojan horse” synthetic nanocarrier system that enters dopaminergic neurons through NTS receptor internalization to deliver a genetic cargo. The success of preclinical studies with different neurotrophic genes supports the possibility of using NTS-polyplex in nanomedicine. In this review, we describe the mechanism of NTS-polyplex transfection. We discuss the concept that an effective neurotrophic therapy requires a simultaneous effect on the axon terminals and soma of the remaining dopaminergic neurons. We also discuss the future of this strategy for the treatment of Parkinson’s disease. PMID:22406187

  9. Comparison of optical coherence tomography findings and visual field changes in patients with primary open-angle glaucoma and amyotrophic lateral sclerosis.

    PubMed

    Liu, Ziyuan; Wang, Hongli; Fan, Dongsheng; Wang, Wei

    2018-02-01

    Recent studies revealing genetic connection of primary open angle glaucoma (POAG) and amyotrophic lateral sclerosis (ALS) have received particular attention. Exploring the evidence for common pathogenesis of these two progressive neurological disorders may assist in understanding the mechanism and searching for new treatment. Retinal nerve fiber layer (RNFL) defect and corresponding visual field (VF) impairment are well known neuropathy signs in glaucoma. In our study, thickness of certain retinal layer in ALS patients was analyzed to detect ganglion cell's soma and axon, and for first time visual field was examined for ALS. The correlation of retinal involvement and ALS progression were also investigated. The results were compared with those of POAG. The study may provide new knowledge for these two neurodegenerative diseases. Copyright © 2017 Elsevier Ltd. All rights reserved.

  10. Angiotensin II regulation of neuromodulation: downstream signaling mechanism from activation of mitogen-activated protein kinase.

    PubMed

    Lu, D; Yang, H; Raizada, M K

    1996-12-01

    Angiotensin II (Ang II) stimulates expression of tyrosine hydroxylase and norepinephrine transporter genes in brain neurons; however, the signal-transduction mechanism is not clearly defined. This study was conducted to determine the involvement of the mitogen-activated protein (MAP) kinase signaling pathway in Ang II stimulation of these genes. MAP kinase was localized in the perinuclear region of the neuronal soma. Ang II caused activation of MAP kinase and its subsequent translocation from the cytoplasmic to nuclear compartment, both effects being mediated by AT1 receptor subtype. Ang II also stimulated SRE- and AP1-binding activities and fos gene expression and its translocation in a MAP kinase-dependent process. These observations are the first demonstration of a downstream signaling pathway involving MAP kinase in Ang II-mediated neuromodulation in noradrenergic neurons.

  11. Transgenerational inheritance of an acquired small RNA-based antiviral response in C.elegans

    PubMed Central

    Rechavi, Oded; Minevich, Gregory; Hobert, Oliver

    2011-01-01

    Induced expression of the Flock House virus in the soma of C. elegans results in the RNAi-dependent production of virus-derived, small interfering RNAs (viRNAs), which in turn silence the viral genome. We show here that the viRNA-mediated viral silencing effect is transmitted in a non-Mendelian manner to many ensuing generations. We show that the viral silencing agents, viRNAs, are transgenerationally transmitted in a template-independent manner and work in trans to silence viral genomes present in animals that are deficient in producing their own viRNAs. These results provide evidence for the transgenerational inheritance of an acquired trait, induced by the exposure of animals to a specific, biologically relevant physiological challenge. The ability to inherit such extragenic information may provide adaptive benefits to an animal. PMID:22119442

  12. Germline V repertoires: Origin, maintenance, diversification.

    PubMed

    Steele, E J; Lindley, R A

    2018-06-01

    In our view, Melvin Cohn (Scand J Immunol. 2018;87:e12640) has set out the logical guidelines towards a resolution of the very real enigma of the selectability of vertebrate germline Ig V repertoires under the current evolutionary paradigm…" A somatically derived repertoire scrambles this (germline VL + VH) substrate so that its specificities are lost, making it un-selectable in the germline. Consequently, evolution faced an incompatibility." It is argued here in Reply that a reverse transcriptase-based soma-to-germline process (S->G) targeting germline V segment arrays goes some considerable way to resolving fundamental contradictions on the origin, maintenance and then real-time adaptive diversification of these limited sets of V segments encoded within various V repertoire arrays. © 2018 The Foundation for the Scandinavian Journal of Immunology.

  13. Evolutionary and mechanistic theories of aging.

    PubMed

    Hughes, Kimberly A; Reynolds, Rose M

    2005-01-01

    Senescence (aging) is defined as a decline in performance and fitness with advancing age. Senescence is a nearly universal feature of multicellular organisms, and understanding why it occurs is a long-standing problem in biology. Here we present a concise review of both evolutionary and mechanistic theories of aging. We describe the development of the general evolutionary theory, along with the mutation accumulation, antagonistic pleiotropy, and disposable soma versions of the evolutionary model. The review of the mechanistic theories focuses on the oxidative stress resistance, cellular signaling, and dietary control mechanisms of life span extension. We close with a discussion of how an approach that makes use of both evolutionary and molecular analyses can address a critical question: Which of the mechanisms that can cause variation in aging actually do cause variation in natural populations?

  14. Fourth revolution in psychiatry – Addressing comorbidity with chronic physical disorders

    PubMed Central

    Gautam, Shiv

    2010-01-01

    The moral treatment of mental patients, Electro Convulsive therapy (ECT), and Psychotropic medications constitute the first, second, and third revolution in psychiatry, respectively. Addressing comorbidities of mental illnesses with chronic physical illnesses will be the fourth revolution in psychiatry. Mind and body are inseparable; there is a bidirectional relationship between psyche and soma, each influencing the other. Plausible biochemical explanations are appearing at an astonishing rate. Psychiatric comorbidity with many chronic physical disorders has remained neglected. Such comorbidity with cardiac, respiratory, Gastrointestinal, endocrinal, and neurological disorders, trauma, and other conditions like HIV and so on, needs to be addressed too. Evidence base of prevalence and causal relationship of psychiatric comorbidities in these disorders has been highlighted and strategies to meet the challenge of comorbidity have been indicated. PMID:21180405

  15. Determination of Low Level Alpha and Beta Emitters Using Liquid-Liquid Extraction and a Liquid Scintillation Spectrometer

    NASA Astrophysics Data System (ADS)

    Yu, Yu-Fu; BjØRnstad, H. E.; Salbu, B.

    Two radiochemical procedures for determination of low level strontium-90 and plutonium-239+240 in environmental and biological materials using combined selective solvent extraction with low level liquid scintillation counting have been presented. Y-90, the daughter nuclide of Sr-90, and Pu-239+240 are selectively extracted from nitric acid solution into 5% di(-2ethylhexyl)phosphoric acid (HDEHP) in toluene and the radionuclides of interest in organic phase are counted with an ultra low level scintillation counter "Quantulus". The lower detection limits for Sr-90 and Pu-239+240 are estimated to be 20 mBq and 0.3 mBq respectively. The developed procedures have been tested for soma environmental and biological samples and the preminarly results show that they are more simple and time-saving than traditional methods.

  16. Genetics and epigenetics of aging and longevity

    PubMed Central

    Moskalev, Alexey A; Aliper, Alexander M; Smit-McBride, Zeljka; Buzdin, Anton; Zhavoronkov, Alex

    2014-01-01

    Evolutionary theories of aging predict the existence of certain genes that provide selective advantage early in life with adverse effect on lifespan later in life (antagonistic pleiotropy theory) or longevity insurance genes (disposable soma theory). Indeed, the study of human and animal genetics is gradually identifying new genes that increase lifespan when overexpressed or mutated: gerontogenes. Furthermore, genetic and epigenetic mechanisms are being identified that have a positive effect on longevity. The gerontogenes are classified as lifespan regulators, mediators, effectors, housekeeping genes, genes involved in mitochondrial function, and genes regulating cellular senescence and apoptosis. In this review we demonstrate that the majority of the genes as well as genetic and epigenetic mechanisms that are involved in regulation of longevity are highly interconnected and related to stress response. PMID:24603410

  17. Polarized trafficking: the palmitoylation cycle distributes cytoplasmic proteins to distinct neuronal compartments.

    PubMed

    Tortosa, Elena; Hoogenraad, Casper C

    2018-02-01

    In neurons, polarized cargo distribution occurs mainly between the soma and axonal and dendritic compartments, and requires coordinated regulation of cytoskeletal remodeling and membrane trafficking. The Golgi complex plays a critical role during neuronal polarization and secretory trafficking has been shown to differentially transport proteins to both axons and dendrites. Besides the Golgi protein sorting, recent data revealed that palmitoylation cycles are an efficient mechanism to localize cytoplasmic, non-transmembrane proteins to particular neuronal compartments, such as the newly formed axon. Palmitoylation allows substrate proteins to bind to and ride with Golgi-derived secretory vesicles to all neuronal compartments. By allowing cytoplasmic proteins to 'hitchhike' on transport carriers in a non-polarized fashion, compartmentalized depalmitoylation may act as a selective retention mechanism. Copyright © 2018 Elsevier Ltd. All rights reserved.

  18. Laser mass spectrometry for DNA fingerprinting for forensic applications

    DOE Office of Scientific and Technical Information (OSTI.GOV)

    Chen, C.H.; Tang, K.; Taranenko, N.I.

    The application of DNA fingerprinting has become very broad in forensic analysis, patient identification, diagnostic medicine, and wildlife poaching, since every individual`s DNA structure is identical within all tissues of their body. DNA fingerprinting was initiated by the use of restriction fragment length polymorphisms (RFLP). In 1987, Nakamura et al. found that a variable number of tandem repeats (VNTR) often occurred in the alleles. The probability of different individuals having the same number of tandem repeats in several different alleles is very low. Thus, the identification of VNTR from genomic DNA became a very reliable method for identification of individuals.more » DNA fingerprinting is a reliable tool for forensic analysis. In DNA fingerprinting, knowledge of the sequence of tandem repeats and restriction endonuclease sites can provide the basis for identification. The major steps for conventional DNA fingerprinting include (1) specimen processing (2) amplification of selected DNA segments by PCR, and (3) gel electrophoresis to do the final DNA analysis. In this work we propose to use laser desorption mass spectrometry for fast DNA fingerprinting. The process and advantages are discussed.« less

  19. Behavioral reactions in rats exposed to low-energy laser radiation

    NASA Astrophysics Data System (ADS)

    Sieron, Aleksander; Mrowiec, Janina; Plech, Andrzej; Cieslar, Grzegorz; Biniszkiewicz, Tomasz

    1995-03-01

    The effect on their behavior of chronic exposure to infrared laser radiation applied to the skull of rats was evaluated. The experiment was carried out on 20 Wistar white male rats. A semiconductive infrared laser (wavelength -- 904 nm, frequency -- 100 Hz, pulse duration -- 10 ns, mean power 10 mW, energy density 1.5 J/cm2) was used. A skull fornix of rats was irradiated with use of multidiode probe, 10 minutes daily for 14 consecutive days. A locomotor activity was determined in the `open field' test. Simultaneously, an exploratory activity was examined in the `hole' test. Space memory was determined by means of a water maze test. Afterwards, an irritability was investigated by means of the score of Nakamura and Thoenen. The evaluation of behavior was made 24 hours after a single irradiation, at the 7th and 14th day of repeated everyday irradiation and then at the 7th and 14th day after the end of the cycle of irradiations. Obtained data show that low-energy laser radiation does not affect the rats central nervous system, resulting in persistent changes of behavior.

  20. Boltzmann Calculations of Electron Transport in CF4 and CF_4/Ar

    NASA Astrophysics Data System (ADS)

    Wang, Yicheng; van Brunt, R. J.

    1996-10-01

    A new set of electron collisional cross sections(L. G. Christophorou, J. K. Olthoff, and M. V. V. S. Rao, J. Phys. Chem. Ref. Data, submitted (May 1996)) for CF4 has been proposed, based primarily upon available experimental measurements. In this paper we present the results of calculations of the drift velocity, ionization coefficient, and attachment coefficient for electrons in CF4 based upon the new cross section set, using a two-term Boltzmann calculation. Comparison of results with experimental determinations of the transport parameters, such as drift velocity, are presented, along with comparison of results obtained using two previously pubished(M. Hyashi, in Swarm Studies and Elastic Electron-Molecule Collisions) (1987); and Y. Nakamura in Gaseous Electronics and Their Applications (1991) electron impact cross section sets for CF_4. Additions and adjustments to the cross section sets required for the model to achieve consitency with transport data are discussed. - Research sponsored in part by the U.S. Air Force Wright Laboratory under contract F33615-96-C-2600 with the University of Tennessee. Also, Department of Physics, The University of Tennessee, Knoxville, TN.

  1. A non-Hermitian analysis of strongly correlated quantum systems

    NASA Astrophysics Data System (ADS)

    Nakamura, Yuichi; Hatano, Naomichi

    2006-03-01

    We study a non-Hermitian generalization of strongly correlated quantum systems in which the transfer energy of electrons is asymmetric. Hatano and Nelson[1] applied this technique to non-interacting random electron systems. They related a non-Hermitian critical point to the inverse localization length of the Hermitian systems. We here conjecture that we can obtain in the same way the correlation length of Hermitian interacting non-random systems[2]. We show for the Hubbard model and the antiferromagnetic XXZ model in one dimension that the non-Hermitian critical point of the ground state, where the energy gap vanishes, is equal to the inverse correlation length. We also show that the conjecture is consistent with numerical results for S=1/2 frustrated quantum spin chains with the nearest- and next-nearest-neighbor interactions including the Majumdar-Ghosh model[3]. [1] N. Hatano and D. R. Nelson, PRL 77 (1996) 570; PRB 56 (1997) 8651. [2] Y. Nakamura and N. Hatano, Physica B, accepted. [3] C. K. Majumdar and D. K. Ghosh, J. Phys. C3 (1970) 911; J. Math. Phys. 10 (1969) 1388, 1399.

  2. Cot kinase promotes Ca2+ oscillation/calcineurin-independent osteoclastogenesis by stabilizing NFATc1 protein.

    PubMed

    Kuroda, Yukiko; Hisatsune, Chihiro; Mizutani, Akihiro; Ogawa, Naoko; Matsuo, Koichi; Mikoshiba, Katsuhiko

    2012-07-01

    Osteoclasts are multinuclear bone-resorbing cells formed by the fusion of monocyte/macrophage-lineage precursor cells. Activation of the transcription factor NFATc1 (nuclear factor of activated T cells c1) by the receptor activator of NF-κB ligand (RANKL) is critical for osteoclast differentiation. In our previous report (Y. Kuroda, C. Hisatsune, T. Nakamura, K. Matsuo, and K. Mikoshiba. Proc. Natl. Acad. Sci. U. S. A. 105:8643, 2008), we demonstrated that osteoblasts induce osteoclast differentiation via Ca(2+) oscillation/calcineurin-dependent and -independent NFATc1 activation pathways; however, the mechanism underlying the latter remained unclear. Here we show that Cot, a serine/threonine kinase also known as tumor progression locus 2 (Tpl-2), directly phosphorylates all Ca(2+)/calcineurin-regulated NFAT family members (NFATc1 through NFATc4) and increases their protein levels. Moreover, Cot activity in osteoclasts was enhanced via cell-cell interaction with osteoblasts, and Cot promoted Ca(2+) oscillation/calcineurin-independent osteoclastogenesis by increasing NFATc1 stability through phosphorylation. We propose that NFAT activation in vivo occurs via phosphorylation-induced protein stabilization, even in the absence of Ca(2+) oscillation and calcineurin activity.

  3. Cot Kinase Promotes Ca2+ Oscillation/Calcineurin-Independent Osteoclastogenesis by Stabilizing NFATc1 Protein

    PubMed Central

    Kuroda, Yukiko; Hisatsune, Chihiro; Mizutani, Akihiro; Ogawa, Naoko

    2012-01-01

    Osteoclasts are multinuclear bone-resorbing cells formed by the fusion of monocyte/macrophage-lineage precursor cells. Activation of the transcription factor NFATc1 (nuclear factor of activated T cells c1) by the receptor activator of NF-κB ligand (RANKL) is critical for osteoclast differentiation. In our previous report (Y. Kuroda, C. Hisatsune, T. Nakamura, K. Matsuo, and K. Mikoshiba. Proc. Natl. Acad. Sci. U. S. A. 105:8643, 2008), we demonstrated that osteoblasts induce osteoclast differentiation via Ca2+ oscillation/calcineurin-dependent and -independent NFATc1 activation pathways; however, the mechanism underlying the latter remained unclear. Here we show that Cot, a serine/threonine kinase also known as tumor progression locus 2 (Tpl-2), directly phosphorylates all Ca2+/calcineurin-regulated NFAT family members (NFATc1 through NFATc4) and increases their protein levels. Moreover, Cot activity in osteoclasts was enhanced via cell-cell interaction with osteoblasts, and Cot promoted Ca2+ oscillation/calcineurin-independent osteoclastogenesis by increasing NFATc1 stability through phosphorylation. We propose that NFAT activation in vivo occurs via phosphorylation-induced protein stabilization, even in the absence of Ca2+ oscillation and calcineurin activity. PMID:22615493

  4. Regulation of flagellar assembly by glycogen synthase kinase 3 in Chlamydomonas reinhardtii.

    PubMed

    Wilson, Nedra F; Lefebvre, Paul A

    2004-10-01

    Chlamydomonas reinhardtii controls flagellar assembly such that flagella are of an equal and predetermined length. Previous studies demonstrated that lithium, an inhibitor of glycogen synthase kinase 3 (GSK3), induced flagellar elongation, suggesting that a lithium-sensitive signal transduction pathway regulated flagellar length (S. Nakamura, H. Takino, and M. K. Kojima, Cell Struct. Funct. 12:369-374, 1987). Here, we demonstrate that lithium treatment depletes the pool of flagellar proteins from the cell body and that the heterotrimeric kinesin Fla10p accumulates in flagella. We identify GSK3 in Chlamydomonas and demonstrate that its kinase activity is inhibited by lithium in vitro. The tyrosine-phosphorylated, active form of GSK3 was enriched in flagella and GSK3 associated with the axoneme in a phosphorylation-dependent manner. The level of active GSK3 correlated with flagellar length; early during flagellar regeneration, active GSK3 increased over basal levels. This increase in active GSK3 was rapidly lost within 30 min of regeneration as the level of active GSK3 decreased relative to the predeflagellation level. Taken together, these results suggest a possible role for GSK3 in regulating the assembly and length of flagella.

  5. Unconventional Fermi surface associated with novel quasiparticles in the Kondo insulator SmB6

    NASA Astrophysics Data System (ADS)

    Sebastian, Suchitra

    The search for a Fermi surface in the absence of a Fermi liquid has endured for decades. We present evidence for the realisation of such a state in the Kondo Insulator SmB6, which is an extreme example of Fermi liquid breakdown. Experimental results are presented from complementary techniques including quantum oscillations, specific heat capacity, thermal conductivity, and oscillatory entropy down to low temperatures. An experimental comparison is made with alternative theoretical models that associate novel quasiparticles with the unconventional Fermi surface we uncover in SmB6. A new paradigm for the realisation of a Fermi surface in the absence of conventional quasiparticles is proposed in the vicinity of a Kondo insulator transition. This work was performed in collaboration with M. Hartstein, W. H. Toews, Y.-T. Hsu, B. Zeng, X. Chen, M. Ciomaga Hatnean, Q. R. Zhang, S. Nakamura, A. S. Padgett, G. Rodway-Gant, J. Berk, M. K. Kingston, G. H. Zhang, M. K. Chan, S. Yamashita, T. Sakakibara, Y. Takano, J. -H. Park, L. Balicas, N. Harrison, N. Shitsevalova, G. Balakrishnan, G. G. Lonzarich, R. W. Hill, and M. Sutherland.

  6. A regularization corrected score method for nonlinear regression models with covariate error.

    PubMed

    Zucker, David M; Gorfine, Malka; Li, Yi; Tadesse, Mahlet G; Spiegelman, Donna

    2013-03-01

    Many regression analyses involve explanatory variables that are measured with error, and failing to account for this error is well known to lead to biased point and interval estimates of the regression coefficients. We present here a new general method for adjusting for covariate error. Our method consists of an approximate version of the Stefanski-Nakamura corrected score approach, using the method of regularization to obtain an approximate solution of the relevant integral equation. We develop the theory in the setting of classical likelihood models; this setting covers, for example, linear regression, nonlinear regression, logistic regression, and Poisson regression. The method is extremely general in terms of the types of measurement error models covered, and is a functional method in the sense of not involving assumptions on the distribution of the true covariate. We discuss the theoretical properties of the method and present simulation results in the logistic regression setting (univariate and multivariate). For illustration, we apply the method to data from the Harvard Nurses' Health Study concerning the relationship between physical activity and breast cancer mortality in the period following a diagnosis of breast cancer. Copyright © 2013, The International Biometric Society.

  7. Comparison of Ab initio Low-Energy Models for LaFePO, LaFeAsO, BaFe2As2, LiFeAs, FeSe, and FeTe

    NASA Astrophysics Data System (ADS)

    Nakamura, Kazuma; Miyake, Takashi; Arita, Ryotaro; Imada, Masatoshi

    2010-03-01

    We present effective low-energy models for LaFePO and LaFeAsO (1111 family), BaFe2As2 (122), LiFeAs (111), and FeSe and FeTe (11) [1], based on ab initio downfolding scheme, a constrained random-phase-approximation method combined with maximally localized Wannier functions. Comparison among the effective models, derived for 5 Fe-3d bands, provides a basis for interpreting physics/chemistry; material dependences of electron correlations, a multiband character entangled by the 3d orbitals, and the geometrical frustration depending on hybridizations between iron and pnictogen/chalcogen orbitals. We found that LaFePO in the 1111 family resides in the weak correlation regime, while LaFeAsO and 111/122 compounds are the intermediate region and FeSe and FeTe in the 11 family are located in the strong correlation regime. A principal parameter relevant to the physics is clarified to be the pnictogen/chalcogen height from the iron layer. Implications in low-energy properties including magnetism and superconductivity are discussed. [1] T. Miyake, K. Nakamura, R. Arita, and M. Imada, arXiv:0911.3705.

  8. Inflammatory myoglandular colorectal polyps: a series of seven cases and review of literature.

    PubMed

    Becheanu, G; Gheorghe, C; Dumbravă, M; Serban-Barbu, V; Diculescu, M

    2011-01-01

    Inflammatory myoglandular polyp is an unusual but distinct, non-neoplastic type of colorectal polyp, commonly with a distal localization at the recto-sigmoidian level. It was first described in 1992 by Nakamura and his colleagues and it is considered to have few particular histological features. We report a series of seven cases (two male and five female patients) of myoglandular polyps with different localization from 15 to 40 cm from anus. Only four out of seven cases presented with rectal bleeding, the others polyps we incidentally discovered. The polyps varied between 4 and 30 mm in the maximum diameter. Grossly, they had firm consistency and smooth reddish surface. Histological examination of the specimens revealed hyperplastic glands with occasional cystic dilatation, proliferation of smooth muscle with no regular distribution, a variable amount of granulation tissue (usually minimal) and no evidence of epithelial dysplasia. All the lesions were removed endoscopically without any complications. Inflammatory myoglandular polyps are distinct histopathological entities, with insufficiently investigated pathogenesis that can include local trauma, mucosal prolapse or ischemia. Being benign they can be removed endoscopically, surgical treatment being reserved in selected cases.

  9. Letter to the editor concerning the article "Bar velocities capable of optimising the muscle power in strength-power exercises" by Loturco, Pereira, Abad, Tabares, Moraes, Kobal, Kitamura & Nakamura (2017).

    PubMed

    Jaric, Slobodan; Garcia Ramos, Amador

    2018-05-01

    Loturco and co-workers (2017) recently published data in the Journal of Sports Sciences to present the optimum loading magnitudes regarding the maximization of the "mean propulsive power" of the leg and arm muscles. Among the most important findings were that (1) the recorded power in the squat and squat jump exercises was markedly low, (2) the optimum external load that maximized the power in the same exercises was close to 100% of body weight, while (3) the ballistic bench press throw revealed smaller power than the regular bench press typically performed with relatively low level of muscle activation towards the end of the propulsive lifting phase. The findings are either counter-intuitive, or contradict the literature findings, or both, and we believe that they originate from apparent methodological flaws. The first one is neglecting the force acting against the body segments moved together with the external load that is particularly high in squat exercises. The second one is an erroneous calculation of the propulsive phase that included a part of the bar's flight time. Both of these methodological flaws are frequent in the literature and could be associated with the improper use and calculation of variables when utilizing linear position transducers.

  10. Perpendicular recording media for hard disk drives

    NASA Astrophysics Data System (ADS)

    Piramanayagam, S. N.

    2007-07-01

    Perpendicular recording technology has recently been introduced in hard disk drives for computer and consumer electronics applications. Although conceptualized in the late 1970s, making a product with perpendicular recording that has competing performance, reliability, and price advantage over the prevalent longitudinal recording technology has taken about three decades. One reason for the late entry of perpendicular recording is that the longitudinal recording technology was quite successful in overcoming many of its problems and in staying competitive. Other reasons are the risks, problems, and investment needed in making a successful transition to perpendicular recording technology. Iwasaki and co-workers came up with many inventions in the late 1970s, such as single-pole head, CoCr alloy media with a perpendicular anisotropy, and recording media with soft magnetic underlayers [S. Iwasaki and K. Takemura, IEEE Trans. Magn. 11, 1173 (1975); S. Iwasaki and Y. Nakamura, IEEE Trans. Magn. 14, 436 (1978); S. Iwasaki, Y. Nakamura, and K. Ouchi, IEEE Trans. Magn. 15, 1456 (1979)]. Nevertheless, the research on perpendicular recording media has been intense only in the past five years or so. The main reason for the current interest comes from the need to find an alternative technology to get away from the superparamagnetic limit faced by the longitudinal recording. Out of the several recording media materials investigated in the past, oxide based CoCrPt media have been considered a blessing. The media developed with CoCrPt-oxide or CoCrPt -SiO2 have shown much smaller grain sizes, lower noise, and larger thermal stability than the perpendicular recording media of the past, which is one of the reasons for the success of perpendicular recording. Moreover, oxide-based perpendicular media have also overtaken the current longitudinal recording media in terms of better recording performance. Several issues that were faced with the soft underlayers have also been solved by the

  11. Heredity as transmission of information: Butlerian 'Intelligent Design.'.

    PubMed

    Forsdyke, Donald R

    2006-01-01

    In the 1870s, Ewald Hering and Samuel Butler provided what was, for that time, a scientifically coherent foundation for the Lamarckist view that positive adaptations to the environment acquired during an individual's lifetime can be transmitted to the offspring. Observing that heredity was a form of memory (involving stored information), they distinguished what are now known as genotype and phenotype and proposed that cognitive abilities present in the the most elementary organisms might mediate a transmission of acquired adaptations. While compatible with the then-available facts of evolution, this Butlerian version of 'intelligent design' was rendered less credible by subsequent appreciations of the discrete (discontinuous) inheritance of many phenotypic characters (Mendelism) and of the separation of germ line from soma (Weismanism). However, it can now be seen that 21st-century bioinformatics has 19th-century roots.

  12. Beyond society: the evolution of organismality

    PubMed Central

    Queller, David C.; Strassmann, Joan E.

    2009-01-01

    The evolution of organismality is a social process. All organisms originated from groups of simpler units that now show high cooperation among the parts and are nearly free of conflicts. We suggest that this near-unanimous cooperation be taken as the defining trait of organisms. Consistency then requires that we accept some unconventional organisms, including some social insect colonies, some microbial groups and viruses, a few sexual partnerships and a number of mutualistic associations. Whether we call these organisms or not, a major task is to explain such cooperative entities, and our survey suggests that many of the traits commonly used to define organisms are not essential. These non-essential traits include physical contiguity, indivisibility, clonality or high relatedness, development from a single cell, short-term and long-term genetic cotransmission, germ–soma separation and membership in the same species. PMID:19805423

  13. Gold rush - A swarm dynamics in games

    NASA Astrophysics Data System (ADS)

    Zelinka, Ivan; Bukacek, Michal

    2017-07-01

    This paper is focused on swarm intelligence techniques and its practical use in computer games. The aim is to show how a swarm dynamics can be generated by multiplayer game, then recorded, analyzed and eventually controlled. In this paper we also discuss possibility to use swarm intelligence instead of game players. Based on our previous experiments two games, using swarm algorithms are mentioned briefly here. The first one is strategy game StarCraft: Brood War, and TicTacToe in which SOMA algorithm has also take a role of player against human player. Open research reported here has shown potential benefit of swarm computation in the field of strategy games and players strategy based on swarm behavior record and analysis. We propose new game called Gold Rush as an experimental environment for human or artificial swarm behavior and consequent analysis.

  14. Dynamics and morphometric characterization of hippocampus neurons using digital holographic microscopy

    NASA Astrophysics Data System (ADS)

    Elkatlawy, Saeid; Gomariz, María.; Soto-Sánchez, Cristina; Martínez Navarrete, Gema; Fernández, Eduardo; Fimia, Antonio

    2014-05-01

    In this paper we report on the use of digital holographic microscopy for 3D real time imaging of cultured neurons and neural networks, in vitro. Digital holographic microscopy is employed as an assessment tool to study the biophysical origin of neurodegenerative diseases. Our study consists in the morphological characterization of the axon, dendrites and cell bodies. The average size and thickness of the soma were 21 and 13 μm, respectively. Furthermore, the average size and diameter of some randomly selected neurites were 4.8 and 0.89 μm, respectively. In addition, the spatiotemporal growth process of cellular bodies and extensions was fitted to by a non-linear behavior of the nerve system. Remarkably, this non-linear process represents the relationship between the growth process of cellular body with respect to the axon and dendrites of the neurons.

  15. Transcriptional regulation of neuronal polarity and morphogenesis in the mammalian brain

    PubMed Central

    de la Torre-Ubieta, Luis; Bonni, Azad

    2012-01-01

    The highly specialized morphology of a neuron, typically consisting of a long axon and multiple branching dendrites, lies at the core of the principle of dynamic polarization, whereby information flows from dendrites toward the soma and to the axon. For more than a century neuroscientists have been fascinated by how shape is important for neuronal function and how neurons acquire their characteristic morphology. During the past decade, substantial progress has been made in our understanding of the molecular underpinnings of neuronal polarity and morphogenesis. In these studies, transcription factors have emerged as key players governing multiple aspects of neuronal morphogenesis from neuronal polarization and migration to axon growth and pathfinding to dendrite growth and branching to synaptogenesis. In this review, we will highlight the role of transcription factors in shaping neuronal morphology with emphasis on recent literature in mammalian systems. PMID:21982366

  16. The actin-binding protein profilin is required for germline stem cell maintenance and germ cell enclosure by somatic cyst cells

    PubMed Central

    Shields, Alicia R.; Spence, Allyson C.; Yamashita, Yukiko M.; Davies, Erin L.; Fuller, Margaret T.

    2014-01-01

    Specialized microenvironments, or niches, provide signaling cues that regulate stem cell behavior. In the Drosophila testis, the JAK-STAT signaling pathway regulates germline stem cell (GSC) attachment to the apical hub and somatic cyst stem cell (CySC) identity. Here, we demonstrate that chickadee, the Drosophila gene that encodes profilin, is required cell autonomously to maintain GSCs, possibly facilitating localization or maintenance of E-cadherin to the GSC-hub cell interface. Germline specific overexpression of Adenomatous Polyposis Coli 2 (APC2) rescued GSC loss in chic hypomorphs, suggesting an additive role of APC2 and F-actin in maintaining the adherens junctions that anchor GSCs to the niche. In addition, loss of chic function in the soma resulted in failure of somatic cyst cells to maintain germ cell enclosure and overproliferation of transit-amplifying spermatogonia. PMID:24346697

  17. Productive infection of HUVEC by HHV-8 is associated with changes compatible with angiogenic transformations.

    PubMed

    Foglieni, C; Scabini, S; Belloni, D; Broccolo, F; Lusso, P; Malnati, M S; Ferrero, E

    2005-01-01

    Kaposi's Sarcoma (KS) is an angioproliferative disease associated with human herpesvirus 8 (HHV-8) infection. We have characterized the morphologic and phenotypic modifications of HUVEC in a model of productive HHV-8 infection. HHV-8 replication was associated with ultra-structural changes, flattened soma and a loss of marginal folds and intercellular contacts, and morphologic features, spindle cell conversion and cordon-like structures formation. Phenotypic changes observed on cordon-like structures included partial loss and redistribution of CD31/PECAM-1 and VE-cadherin, uPAR up-regulation and de novo expression of CD13/APN. Such changes demonstrate the induction, in HUVEC, of an angiogenic profile. Most of these findings are directly linked to HHV-8-encoded proteins expression, suggesting that HHV-8 itself may participate to the initial steps of the angiogenic transformation in KS.

  18. Tau-mediated synaptic and neuronal dysfunction in neurodegenerative disease.

    PubMed

    Tracy, Tara E; Gan, Li

    2018-05-09

    The accumulation of pathological tau in the brain is associated with neuronal deterioration and cognitive impairments in tauopathies including Alzheimer's disease. Tau, while primarily localized in the axons of healthy neurons, accumulates in the soma and dendrites of neurons under pathogenic conditions. Tau is found in both presynaptic and postsynaptic compartments of neurons in Alzheimer's disease. New research supports that soluble forms of tau trigger pathophysiology in the brain by altering properties of synaptic and neuronal function at the early stages of disease progression, before neurons die. Here we review the current understanding of how tau-mediated synaptic and neuronal dysfunction contributes to cognitive decline. Delineating the mechanisms by which pathogenic tau alters synapses, dendrites and axons will help lay the foundation for new strategies that can restore neuronal function in tauopathy. Copyright © 2018 Elsevier Ltd. All rights reserved.

  19. Sex determination in mammalian germ cells

    PubMed Central

    Spiller, Cassy M; Bowles, Josephine

    2015-01-01

    Germ cells are the precursors of the sperm and oocytes and hence are critical for survival of the species. In mammals, they are specified during fetal life, migrate to the developing gonads and then undergo a critical period during which they are instructed, by the soma, to adopt the appropriate sexual fate. In a fetal ovary, germ cells enter meiosis and commit to oogenesis, whereas in a fetal testis, they avoid entry into meiosis and instead undergo mitotic arrest and mature toward spermatogenesis. Here, we discuss what we know so far about the regulation of sex-specific differentiation of germ cells, considering extrinsic molecular cues produced by somatic cells, as well as critical intrinsic changes within the germ cells. This review focuses almost exclusively on our understanding of these events in the mouse model. PMID:25791730

  20. Role of the nuclear envelope in the pathogenesis of age-related bone loss and osteoporosis

    PubMed Central

    Vidal, Christopher; Bermeo, Sandra; Fatkin, Diane; Duque, Gustavo

    2012-01-01

    The nuclear envelope is the most important border in the eukaryotic cell. The role of the nuclear envelope in cell differentiation and function is determined by a constant interaction between the elements of the nuclear envelope and the transcriptional regulators involved in signal transcription pathways. Among those components of the nuclear envelope, there is a growing evidence that changes in the expression of A-type lamins, which are essential components of the nuclear lamina, are associated with age-related changes in bone affecting the capacity of differentiation of mesenchymal stem cells into osteoblasts, favoring adipogenesis and affecting the function and survival of the osteocytes. Overall, as A-type lamins are considered as the 'guardians of the soma', these proteins are also essential for the integrity and quality of the bone and pivotal for the longevity of the musculoskeletal system. PMID:23951459

  1. Late injury of cancer therapy on the female reproductive tract

    DOE Office of Scientific and Technical Information (OSTI.GOV)

    Grigsby, P.W.; Russell, A.; Bruner, D.

    1995-03-30

    The purpose of this article is to review the late effects of cancer therapy on the female reproductive tract. The anatomic sites detailed are the vulva, vagina, cervix, uterus, fallopian tubes, and ovaries. The available pathophysiology is discussed. Clinical syndromes are presented. Tolerance doses of irradiation for late effects are rarely presented in the literature and are reviewed where available. Management strategies for surgical, radiotherapeutic, and chemotherapeutic late effects are discussed. Endpoints for evaluation of therapeutic late effects have been formulated utilizing the symptons, objective, management, and analytic (SOMA) format. Late effects on the female reproductive tract from cancer therapymore » should be recognized and managed appropriately. A grading system for these effects is presented. Endpoints for late effects and tolls for the evaluation need to be further developed. 61 refs., 9 figs., 13 tabs.« less

  2. Respiratory chain deficiency in aged spinal motor neurons☆

    PubMed Central

    Rygiel, Karolina A.; Grady, John P.; Turnbull, Doug M.

    2014-01-01

    Sarcopenia, muscle wasting, and strength decline with age, is an important cause of loss of mobility in the elderly individuals. The underlying mechanisms are uncertain but likely to involve defects of motor nerve, neuromuscular junction, and muscle. Loss of motor neurons with age and subsequent denervation of skeletal muscle has been recognized as one of the contributing factors. This study investigated aspects of mitochondrial biology in spinal motor neurons from elderly subjects. We found that protein components of complex I of mitochondrial respiratory chain were reduced or absent in a proportion of aged motor neurons–a phenomenon not observed in fetal tissue. Further investigation showed that complex I-deficient cells had reduced mitochondrial DNA content and smaller soma size. We propose that mitochondrial dysfunction in these motor neurons could lead to the cell loss and ultimately denervation of muscle fibers. PMID:24684792

  3. Use of rubber and bentonite added fly ash as a liner material.

    PubMed

    Cokca, Erdal; Yilmaz, Zeka

    2004-01-01

    In many countries regulations require all hazardous waste disposal facilities to be lined with suitable impermeable barriers to protect against contamination. In this study, a series of laboratory tests on rubber and bentonite added fly ash were conducted. The aim of the tests was to evaluate the feasibility of utilizing fly ash, rubber and bentonite as a low hydraulic conductivity liner material. Type C fly ash was obtained from Soma thermal power plant in Turkey; rubber in pulverized form was waste from the retreading industry. To investigate the properties of rubber and bentonite added fly ash, hydraulic conductivity, leachate analysis, unconfined compression, split tensile strength, one-dimensional consolidation, swell and freeze/thaw cycle tests were performed. The overall evaluation of results have revealed that rubber and bentonite added fly ash showed good promise and a candidate for construction of a liner.

  4. Germline epimutation in humans.

    PubMed

    Cropley, Jennifer E; Martin, David I K; Suter, Catherine M

    2008-12-01

    Epigenetic modifications provide all multicellular organisms with a system of gene regulation that allows clonally heritable yet reversible alterations in gene transcription. Errors in this complex system can give rise to abnormal gene silencing, termed 'epimutation'; importantly, this can occur in the absence of any underlying genetic defect. Epimutations are commonly somatic events, and are particularly prevalent in tumors, but we and others have shown that epimutation can also arise in the germline, giving rise to soma-wide transcriptional silencing of a gene. A germline epimutation can mimic the effect of an inactivating mutation, and in doing so, can phenocopy a genetic disease. In this article, we will review the recent findings with germline epimutation at the tumor suppressor gene MLH1, discuss the possible etiology of this phenomenon, and the implications of germline epimutation in humans.

  5. Endogenous vs Exogenous Allosteric Modulators in GPCRs: A dispute for shuttling CB1 among different membrane microenvironments

    NASA Astrophysics Data System (ADS)

    Stornaiuolo, Mariano; Bruno, Agostino; Botta, Lorenzo; Regina, Giuseppe La; Cosconati, Sandro; Silvestri, Romano; Marinelli, Luciana; Novellino, Ettore

    2015-10-01

    A Cannabinoid Receptor 1 (CB1) binding site for the selective allosteric modulator ORG27569 is here identified through an integrate approach of consensus pocket prediction, mutagenesis studies and Mass Spectrometry. This unprecedented ORG27569 pocket presents the structural features of a Cholesterol Consensus Motif, a cholesterol interacting region already found in other GPCRs. ORG27569 and cholesterol affects oppositely CB1 affinity for orthosteric ligands. Moreover, the rise in cholesterol intracellular level results in CB1 trafficking to the axonal region of neuronal cells, while, on the contrary, ORG27568 binding induces CB1 enrichment at the soma. This control of receptor migration among functionally different membrane regions of the cell further contributes to downstream signalling and adds a previously unknown mechanism underpinning CB1 modulation by ORG27569 , that goes beyond a mere control of receptor affinity for orthosteric ligands.

  6. Modulating nitric oxide levels in dorsal root ganglion neurons of rat with low-level laser therapy

    NASA Astrophysics Data System (ADS)

    Zheng, Li-qin; Wang, Yu-hua; He, Yi-peng; Zhou, Jie; Yang, Hong-qin; Zhang, Yan-ding; Xie, Shu-sen

    2015-05-01

    Nitric oxide (NO) and nitric oxide synthase (NOS) have an important role in pain signaling transmission in animal models. Low-level laser therapy (LLLT) is known to have an analgesic effect, but the mechanism is unclear. The aim of the study is to investigate the influence of LLLT on NO release and NOS synthesis in dorsal root ganglion (DRG) neurons, in order to find whether LLLI can ameliorate pain through modulating NO production at the cellular level. The results show that in stress conditions, the laser irradiation at 658 nm can modulate NO production in DRG neurons with soma diameter of about 20 μm in a short time after illumination, and affect NOS synthesis in a dose-dependent manner. It is demonstrated that LLLT might treat pain by altering NO release directly and indirectly in DRG neurons.

  7. Superorganismality and caste differentiation as points of no return: how the major evolutionary transitions were lost in translation.

    PubMed

    Boomsma, Jacobus J; Gawne, Richard

    2018-02-01

    More than a century ago, William Morton Wheeler proposed that social insect colonies can be regarded as superorganisms when they have morphologically differentiated reproductive and nursing castes that are analogous to the metazoan germ-line and soma. Following the rise of sociobiology in the 1970s, Wheeler's insights were largely neglected, and we were left with multiple new superorganism concepts that are mutually inconsistent and uninformative on how superorganismality originated. These difficulties can be traced to the broadened sociobiological concept of eusociality, which denies that physical queen-worker caste differentiation is a universal hallmark of superorganismal colonies. Unlike early evolutionary naturalists and geneticists such as Weismann, Huxley, Fisher and Haldane, who set out to explain the acquisition of an unmated worker caste, the goal of sociobiology was to understand the evolution of eusociality, a broad-brush convenience category that covers most forms of cooperative breeding. By lumping a diverse spectrum of social systems into a single category, and drawing attention away from the evolution of distinct quantifiable traits, the sociobiological tradition has impeded straightforward connections between inclusive fitness theory and the major evolutionary transitions paradigm for understanding irreversible shifts to higher organizational complexity. We evaluate the history by which these inconsistencies accumulated, develop a common-cause approach for understanding the origins of all major transitions in eukaryote hierarchical complexity, and use Hamilton's rule to argue that they are directly comparable. We show that only Wheeler's original definition of superorganismality can be unambiguously linked to irreversible evolutionary transitions from context-dependent reproductive altruism to unconditional differentiation of permanently unmated castes in the ants, corbiculate bees, vespine wasps and higher termites. We argue that strictly

  8. Reconstruction of ionic currents in a molluscan photoreceptor.

    PubMed Central

    Sakakibara, M.; Ikeno, H.; Usui, S.; Collin, C.; Alkon, D. L.

    1993-01-01

    Two-microelectrode voltage-clamp measurements were made to determine the kinetics and voltage dependence of ionic currents across the soma membrane of the Hermissenda type B photoreceptor. The voltage-dependent outward potassium currents, IA and ICa(2+)-K+, the inward voltage-dependent calcium current, ICa2+ and the light-induced current, IIgt, were then described with Hodgkin-Huxley-type equations. The fast-activating and inactivating potassium current, IA, was described by the equation; IA(t) = gA(max)(ma infinity[1-exp(-t/tau ma)])3 x (ha infinity [1-exp(-t/tau ha)] + exp(-t/tau ha)) (Vm-EK), where the parameters ma infinity, ha infinity, tau ma, and tau ha are functions of membrane potential, Vm, and ma infinity and ha infinity are steady-state activation and inactivation parameters. Similarly, the calcium-dependent outward potassium current, ICa(2+)-K+, was described by the equation, ICa(2+)-K+ (t) = gc(max)(mc infinity(VC)(1-exp[-t/tau mc (VC)]))pc (hc infinity(VC) [1-exp(-t/tau hc)] + exp(-t/tau hc(VC)])pc(VC-EK). In high external potassium, ICa(2+)-K+ could be measured in approximate isolation from other currents as a voltage-dependent inward tail current following a depolarizing command pulse from a holding potential of -60 mV. A voltage-dependent inward calcium current across the type B soma membrane, ICa2+, activated rapidly, showed little inactivation, and was described by the equation: ICa2+ = gCa(max) [1 + exp](-Vm-5)/7]-1 (Vm-ECa), where gCa(max) was 0.5 microS. The light-induced current with both fast and slow phases was described by: IIgt(t) = IIgt1 + IIgt2 + IIgt3, IIgti = gIgti [1-exp(- ton/tau mi)] exp(-ton/tau hi)(Vm-EIgti) (i = 1, 2). For i = 3, /Igt(t) = gigt3m33h3(Vm - Eigt3)exp(-ton/Ton) x exp(-tfoff/t Off). Based on these reconstructions of ionic currents, learning-induced enhancement of the long lasting depolarization (LLD) of the photoreceptor'slight response was shown to arise from progressive inactivation of /A, lca2+ -K+, and lCa2

  9. Acute Unstable Depressive Syndrome (AUDS) is associated more frequently with epilepsy than major depression.

    PubMed

    Vaaler, Arne E; Morken, Gunnar; Iversen, Valentina C; Kondziella, Daniel; Linaker, Olav M

    2010-07-30

    Depressive disorders are frequent in epilepsy and associated with reduced seizure control. Almost 50% of interictal depressive disorders have to be classified as atypical depressions according to DSM-4 criteria. Research has mainly focused on depressive symptoms in defined populations with epilepsy (e.g., patients admitted to tertiary epilepsy centers). We have chosen the opposite approach. We hypothesized that it is possible to define by clinical means a subgroup of psychiatric patients with higher than expected prevalence of epilepsy and seizures. We hypothesized further that these patients present with an Acute Unstable Depressive Syndrome (AUDS) that does not meet DSM-IV criteria of a Major Depressive Episode (MDE). In a previous publication we have documented that AUDS patients indeed have more often a history of epileptic seizures and abnormal EEG recordings than MDE patients (Vaaler et al. 2009). This study aimed to further classify the differences of depressive symptoms at admittance and follow-up of patients with AUDS and MDE. 16 AUDS patients and 16 age- and sex-matched MDE patients were assessed using the Symptomatic Organic Mental Disorder Assessment Scale (SOMAS), the Montgomery and Asberg Depression Rating Scale (MADRS), and the Mini-Mental State Test (MMST), at day 2, day 4-6, day 14-16 and 3 months after admittance to a psychiatric emergency unit. Life events were assessed with The Social Readjustment Rating Scale (SRRS) and The Life Experience Survey (LES). We also screened for medication serum levels and illicit drug metabolites in urine. AUDS patients had significantly higher SOMAS scores (average score at admission 6.6 +/- 0.8), reflecting increased symptom fluctuation and motor agitation, and decreased insight and concern compared to MDE patients (2.9 +/- 0.7; p < 0.001). Degree of mood depression, cognition, life events, drug abuse and medication did not differ between the two groups. AUDS patients present with rapidly fluctuating mood

  10. Changes in metabolic profiles after the Great East Japan Earthquake: a retrospective observational study.

    PubMed

    Tsubokura, Masaharu; Takita, Morihito; Matsumura, Tomoko; Hara, Kazuo; Tanimoto, Tetsuya; Kobayashi, Kazuhiko; Hamaki, Tamae; Oiso, Giichiro; Kami, Masahiro; Okawada, Tadaichi; Tachiya, Hidekiyo

    2013-03-23

    A magnitude 9.0 earthquake struck off eastern Japan in March 2011. Many survivors have been living in temporary houses provided by the local government since they lost their houses as a result of the great tsunami (tsunami group) or the expected high-dose radiation resulting from the nuclear accident at the Fukushima Daiichi Nuclear Power Plant (radiation group). The tsunami was more than 9 m high in Soma, Fukushima, which is located 30 km north of the Fukushima Daiichi Nuclear Power Plant and adjacent to the mandatory evacuation area. A health screening program was held for the evacuees in Soma in September 2011. The aim of this study was to compare the metabolic profiles of the evacuees before and after the disaster. We hypothesized that the evacuees would experience deteriorated metabolic status based on previous reports of natural disasters. Data on 200 subjects who attended a health screening program in September or October of 2010 (pre-quake) and 2011 (post-quake) were retrospectively reviewed and included in this study. Pre-quake and post-quake results of physical examinations and laboratory tests were compared in the tsunami and radiation groups. A multivariate regression model was used to determine pre-quake predictive factors for elevation of hemoglobin A1c (HbA1c) in the tsunami group. Significantly higher values of body weight, body mass index, waist circumference, and HbA1c and lower high-density lipoprotein cholesterol levels were found at the post-quake screening when compared with the pre-quake levels (p = 0.004, p = 0.03, p = 0.008, p < 0.001, and p = 0.03, respectively). A significantly higher proportion of subjects in the tsunami group with high HbA1c, defined as ≥ 5.7%, was observed after the quake (34.3%) than before the quake (14.8%) (p < 0.001). Regional factors, periodic clinic visits, and waist circumference before the quake were identified as predictive factors on multivariate analysis for the deterioration of HbA1c. Post-quake metabolic

  11. Maternal vitamin D depletion alters DNA methylation at imprinted loci in multiple generations.

    PubMed

    Xue, Jing; Schoenrock, Sarah A; Valdar, William; Tarantino, Lisa M; Ideraabdullah, Folami Y

    2016-01-01

    Environmental perturbation of epigenetic mechanisms is linked to a growing number of diseases. Characterizing the role environmental factors play in modifying the epigenome is important for disease etiology. Vitamin D is an essential nutrient affecting brain, bone, heart, immune and reproductive health. Vitamin D insufficiency is a global issue, and the role in maternal and child health remains under investigation. We used Collaborative Cross (CC) inbred mice to characterize the effect of maternal vitamin D depletion on offspring phenotypic and epigenetic outcomes at imprinted domains ( H19/Igf2 , Snrpn , Dlk1/Gtl2 , and Grb10 ) in the soma (liver) and germline (sperm). We assessed outcomes in two generations of offspring to determine heritability. We used reciprocal crosses between lines CC001/Unc and CC011/Unc to investigate parent of origin effects. Maternal vitamin D deficiency led to altered body weight and DNA methylation in two generations of offspring. Loci assayed in adult liver and sperm were mostly hypomethylated, but changes were few and small in effect size (<7 % difference on average). There was no change in total expression of genes adjacent to methylation changes in neonatal liver. Methylation changes were cell type specific such that changes at IG-DMR were present in sperm but not in liver. Some methylation changes were distinct between generations such that methylation changes at the H19ICR in second-generation liver were not present in first-generation sperm or liver. Interestingly, some diet-dependent changes in body weight and methylation were seemingly influenced by parent of origin such that reciprocal crosses exhibited inverse effects. These findings demonstrate that maternal vitamin D status plays a role in determining DNA methylation state in the germline and soma. Detection of methylation changes in the unexposed second-generation demonstrates that maternal vitamin D depletion can have long-term effects on the epigenome of subsequent

  12. Lissencephaly-1 dependent axonal retrograde transport of L1-type CAM Neuroglian in the adult drosophila central nervous system

    PubMed Central

    Börner, Jana; Slipchuk, Olesya; Kakad, Priyanka; Lee, LaTasha H.; Qureshi, Aater; Pielage, Jan

    2017-01-01

    Here, we established the Drosophila Giant Fiber neurons (GF) as a novel model to study axonal trafficking of L1-type Cell Adhesion Molecules (CAM) Neuroglian (Nrg) in the adult CNS using live imaging. L1-type CAMs are well known for their importance in nervous system development and we previously demonstrated a role for Nrg in GF synapse formation. However, in the adult they have also been implicated in synaptic plasticity and regeneration. In addition, to its canonical role in organizing cytoskeletal elements at the plasma membrane, vertebrate L1CAM has also been shown to regulate transcription indirectly as well as directly via its import to the nucleus. Here, we intend to determine if the sole L1CAM homolog Nrg is retrogradley transported and thus has the potential to relay signals from the synapse to the soma. Live imaging of c-terminally tagged Nrg in the GF revealed that there are at least two populations of retrograde vesicles that differ in speed, and either move with consistent or varying velocity. To determine if endogenous Nrg is retrogradely transported, we inhibited two key regulators, Lissencephaly-1 (Lis1) and Dynactin, of the retrograde motor protein Dynein. Similar to previously described phenotypes for expression of poisonous subunits of Dynactin, we found that developmental knock down of Lis1 disrupted GF synaptic terminal growth and that Nrg vesicles accumulated inside the stunted terminals in both mutant backgrounds. Moreover, post mitotic Lis1 knock down in mature GFs by either RNAi or Clustered Regularly Interspaced Short Palindromic Repeats (CRISPR) induced mutations, resulted in normal length terminals with fully functional GF synapses which also exhibited severe accumulation of endogenous Nrg vesicles. Thus, our data suggests that accumulation of Nrg vesicles is due to failure of retrograde transport rather than a failure of terminal development. Together with the finding that post mitotic knock down of Lis1 also disrupted retrograde

  13. Lissencephaly-1 dependent axonal retrograde transport of L1-type CAM Neuroglian in the adult drosophila central nervous system.

    PubMed

    Kudumala, Sirisha R; Penserga, Tyrone; Börner, Jana; Slipchuk, Olesya; Kakad, Priyanka; Lee, LaTasha H; Qureshi, Aater; Pielage, Jan; Godenschwege, Tanja A

    2017-01-01

    Here, we established the Drosophila Giant Fiber neurons (GF) as a novel model to study axonal trafficking of L1-type Cell Adhesion Molecules (CAM) Neuroglian (Nrg) in the adult CNS using live imaging. L1-type CAMs are well known for their importance in nervous system development and we previously demonstrated a role for Nrg in GF synapse formation. However, in the adult they have also been implicated in synaptic plasticity and regeneration. In addition, to its canonical role in organizing cytoskeletal elements at the plasma membrane, vertebrate L1CAM has also been shown to regulate transcription indirectly as well as directly via its import to the nucleus. Here, we intend to determine if the sole L1CAM homolog Nrg is retrogradley transported and thus has the potential to relay signals from the synapse to the soma. Live imaging of c-terminally tagged Nrg in the GF revealed that there are at least two populations of retrograde vesicles that differ in speed, and either move with consistent or varying velocity. To determine if endogenous Nrg is retrogradely transported, we inhibited two key regulators, Lissencephaly-1 (Lis1) and Dynactin, of the retrograde motor protein Dynein. Similar to previously described phenotypes for expression of poisonous subunits of Dynactin, we found that developmental knock down of Lis1 disrupted GF synaptic terminal growth and that Nrg vesicles accumulated inside the stunted terminals in both mutant backgrounds. Moreover, post mitotic Lis1 knock down in mature GFs by either RNAi or Clustered Regularly Interspaced Short Palindromic Repeats (CRISPR) induced mutations, resulted in normal length terminals with fully functional GF synapses which also exhibited severe accumulation of endogenous Nrg vesicles. Thus, our data suggests that accumulation of Nrg vesicles is due to failure of retrograde transport rather than a failure of terminal development. Together with the finding that post mitotic knock down of Lis1 also disrupted retrograde

  14. Towards a Detailed Seismic Structure of the Valley of Mexico's Xochimilco Lake Zone.

    NASA Astrophysics Data System (ADS)

    Rabade, S.; Sanchez-Sanchez, J.; Ayala Hernandez, M.; Macias, M. A.; Aguilar Calderon, L. A.; Alcántara, L.; Almora Mata, D.; Castro Parra, G.; Delgado, R.; Leonardo Suárez, M.; Molina Avila, I.; Mora, A.; Perez-Yanez, C.; Ruiz, A. L.; Sandoval, H.; Torres Noguez, M.; Vazquez Larquet, R.; Velasco Miranda, J. M.; Aguirre, J.; Ramirez-Guzmán, L.

    2017-12-01

    Six centuries of gradual, intentional sediment filling in the Xochimilco Lake Zone have drastically reduced the size of the lake. The basin structure and the lake's clay limits and thickness are poorly constrained, and yet, essential to explain the city's anomalous ground motion. Therefore, we conducted an experiment to define the 3D velocity model of Mexico's capital; the CDMX-E3D. The initial phase involved the deployment of a moving set of 18-broadband stations with an interstation distance of 500m over a period of 19 weeks. We collected the data and analyzed the results for the Xochimilco Lake Zone using H/V Spectral Ratios (Nakamura, 1989), which provided an improved fundamental period map of the region. Results show that periods in the former lake zone have larger variability than values previously estimated. In order to obtain group velocity maps at different periods, we estimated Green's functions from ambient noise cross-correlations following standard methodologies to invert Rayleigh wave travel times (Bensen et al., 2007). Preliminary result show very low-velocity zones (100 m/s) and thick sediment layers in most of the former Xochimilco Lake area. This Project was funded by the Secretaria de Ciencia, Tecnología e Innovación (SECITI) of Mexico City. Project SECITI/073/2016.

  15. Disaster risk management in prospect mining area Blitar district, East Java, using microtremor analysis and ANP (analytical network processing) approach

    DOE Office of Scientific and Technical Information (OSTI.GOV)

    Parwatiningtyas, Diyan, E-mail: diane.tyas@gmail.com, E-mail: erlinunindra@gmail.com; Ambarsari, Erlin Windia, E-mail: diane.tyas@gmail.com, E-mail: erlinunindra@gmail.com; Marlina, Dwi, E-mail: diane.tyas@gmail.com, E-mail: erlinunindra@gmail.com

    Indonesia has a wealth of natural assets is so large to be managed and utilized, either from its own local government and local communities, especially in the mining sector. However, mining activities can change the state of the surface layer of the earth that have a high impact disaster risk. This could threaten the safety and disrupt human life, environmental damage, loss of property, and the psychological impact, sulking to the rule of law no 24 of 2007. That's why we strive to manage and minimize the risk of mine disasters in the region, how to use the method ofmore » calculation of Amplification Factor (AF) from the analysis based microtremor sulking Kanai and Nakamura, and decision systems were tested by analysis of ANP. Based on the amplification factor and Analytical Network Processing (ANP) obtained, some points showed instability in the surface layer of a mining area include the site of the TP-7, TP-8, TP-9, TP-10, (Birowo2). If in terms of structure, location indicated unstable due to have a sloping surface layer, resulting in the occurrence of landslides and earthquake risk is high. In the meantime, other areas of the mine site can be said to be a stable area.« less

  16. Restoration and Reexamination of Apollo Lunar Dust Detector Data from Original Telemetry Files

    NASA Technical Reports Server (NTRS)

    McBride, M. J.; Williams, David R.; Hills, H. Kent

    2012-01-01

    We are recovering the original telemetry (Figure I) from the Apollo Dust, Thermal, Radiation Environment Monitor (DTREM) experiment, more commonly known as the Dust Detector, and producing full time resolution (54 second) data sets for release through the Planetary Data System (PDS). The primary objective of the experiment was to evaluate the effect of dust deposition, temperature, and radiation damage on solar cells on the lunar surface. The monitor was a small box consisting of three solar cells and thermistors mounted on the ALSEP (Apollo Lunar Surface Experiments Package) central station. The Dust Detector was carried on Apollo's 11, 12, 14 and 15. The Apollo 11 DTREM was powered by solar cells and only operated for a few months as planned. The Apollo 12, 14, and 15 detectors operated for 5 to 7 years, returning data every 54 seconds, consisting of voltage outputs from the three solar cells and temperatures measured by the three thermistors. The telemetry was received at ground stations and held on the Apollo Housekeeping (known as "Word 33") tapes. made available to the National Space Science Data Center (NSSDC) by Yosio Nakamura (University of Texas Institute for Geophysics). We have converted selected parts of the telemetry into uncalibrated and calibrated output voltages and temperatures.

  17. Electronically nonadiabatic wave packet propagation using frozen Gaussian scattering

    DOE Office of Scientific and Technical Information (OSTI.GOV)

    Kondorskiy, Alexey D., E-mail: kondor@sci.lebedev.ru; Nanbu, Shinkoh, E-mail: shinkoh.nanbu@sophia.ac.jp

    2015-09-21

    We present an approach, which allows to employ the adiabatic wave packet propagation technique and semiclassical theory to treat the nonadiabatic processes by using trajectory hopping. The approach developed generates a bunch of hopping trajectories and gives all additional information to incorporate the effect of nonadiabatic coupling into the wave packet dynamics. This provides an interface between a general adiabatic frozen Gaussian wave packet propagation method and the trajectory surface hopping technique. The basic idea suggested in [A. D. Kondorskiy and H. Nakamura, J. Chem. Phys. 120, 8937 (2004)] is revisited and complemented in the present work by the elaborationmore » of efficient numerical algorithms. We combine our approach with the adiabatic Herman-Kluk frozen Gaussian approximation. The efficiency and accuracy of the resulting method is demonstrated by applying it to popular benchmark model systems including three Tully’s models and 24D model of pyrazine. It is shown that photoabsorption spectrum is successfully reproduced by using a few hundreds of trajectories. We employ the compact finite difference Hessian update scheme to consider feasibility of the ab initio “on-the-fly” simulations. It is found that this technique allows us to obtain the reliable final results using several Hessian matrix calculations per trajectory.« less

  18. Itokawa's Opposition Surge seen by Hayabusa/AMICA

    NASA Technical Reports Server (NTRS)

    Dominque, D.; Tatsumi, E.; Vilas, F.; Hirata, N.; Lederer, S.

    2017-01-01

    Using images acquired by the Hayabusa/AMICA instrument, along with Lederer et al.'s (2008) ground-based observations, we re-examine Itokawa's disk-integrated phase curve. The AMICA images provide critical opposition measurements (between 0.7deg - 9.3deg phase at 540 nm). Using Hapke's model (2012), we fit the updated phase curves at 5 different wavelengths. Preliminary modeling results show a range of porosity values commensurate with those in the literature (Ostro et al. 2004, Gundlach and Blum, 2012, Kiuchi and Nakamura 2014) based on an impact-generated grain size distribution function and grain size range evaluations from the AMICA data (Yano et al. 2006). This wide range on a global porosity is indicative of a highly variable porosity across the surface. The derived transport mean free path and the generally forward scattering nature of the global regolith are indicative of scattering centers (such as cracks, bubbles, and inclusions) that are small compared to the observational wavelengths. The derived regolith properties are compared with the imaging and sample analysis results, providing a test of the predictive capabilities of global disk-integrated measurements. This work suggests that the sub-pixel grain information could be extracted from the photometry, especially around opposition.

  19. A numerical study of magnetohydrodynamic transport of nanofluids over a vertical stretching sheet with exponential temperature-dependent viscosity and buoyancy effects

    NASA Astrophysics Data System (ADS)

    Akbar, Noreen Sher; Tripathi, Dharmendra; Khan, Zafar Hayat; Bég, O. Anwar

    2016-09-01

    In this paper, a mathematical study is conducted of steady incompressible flow of a temperature-dependent viscous nanofluid from a vertical stretching sheet under applied external magnetic field and gravitational body force effects. The Reynolds exponential viscosity model is deployed. Electrically-conducting nanofluids are considered which comprise a suspension of uniform dimension nanoparticles suspended in viscous base fluid. The nanofluid sheet is extended with a linear velocity in the axial direction. The Buonjiornio model is utilized which features Brownian motion and thermophoresis effects. The partial differential equations for mass, momentum, energy and species (nano-particle concentration) are formulated with magnetic body force term. Viscous and Joule dissipation effects are neglected. The emerging nonlinear, coupled, boundary value problem is solved numerically using the Runge-Kutta fourth order method along with a shooting technique. Graphical solutions for velocity, temperature, concentration field, skin friction and Nusselt number are presented. Furthermore stream function plots are also included. Validation with Nakamura's finite difference algorithm is included. Increasing nanofluid viscosity is observed to enhance temperatures and concentrations but to reduce velocity magnitudes. Nusselt number is enhanced with both thermal and species Grashof numbers whereas it is reduced with increasing thermophoresis parameter and Schmidt number. The model is applicable in nano-material manufacturing processes involving extruding sheets.

  20. Disaster risk management in prospect mining area Blitar district, East Java, using microtremor analysis and ANP (analytical network processing) approach

    NASA Astrophysics Data System (ADS)

    Parwatiningtyas, Diyan; Ambarsari, Erlin Windia; Marlina, Dwi; Wiratomo, Yogi

    2014-03-01

    Indonesia has a wealth of natural assets is so large to be managed and utilized, either from its own local government and local communities, especially in the mining sector. However, mining activities can change the state of the surface layer of the earth that have a high impact disaster risk. This could threaten the safety and disrupt human life, environmental damage, loss of property, and the psychological impact, sulking to the rule of law no 24 of 2007. That's why we strive to manage and minimize the risk of mine disasters in the region, how to use the method of calculation of Amplification Factor (AF) from the analysis based microtremor sulking Kanai and Nakamura, and decision systems were tested by analysis of ANP. Based on the amplification factor and Analytical Network Processing (ANP) obtained, some points showed instability in the surface layer of a mining area include the site of the TP-7, TP-8, TP-9, TP-10, (Birowo2). If in terms of structure, location indicated unstable due to have a sloping surface layer, resulting in the occurrence of landslides and earthquake risk is high. In the meantime, other areas of the mine site can be said to be a stable area.