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Sample records for thermosensitive cold neuron

  1. Effects of electrical stimulation of ventral septal area on firing rates of pyrogen-treated thermosensitive neurons in preoptic anterior hypothalamus from rabbits.

    Science.gov (United States)

    Dong, Jun; Xie, Xin-Hua; Lu, Da-Xiang; Fu, Yong-Mei

    2007-01-09

    Although there is considerable evidence supporting that fever evolved as a host defense response, it is important that the rise in body temperature would not be too high. Many endogenous cryogens or antipyretics that limit the rise in body temperature have been identified. Endogenous antipyretics attenuate fever by influencing the thermoregulatory neurons in the preoptic anterior hypothalamus (POAH) and in adjacent septal areas including ventral septal area (VSA). Our previous study showed that intracerebroventricular (I.C.V.) injection of interleukin-1beta (IL-1beta) affected electrophysiological activities of thermosensitive neurons in VSA regions, and electrical stimulation of POAH reversed the effect of IL-1beta. To further investigate the functional electrophysiological connection between POAH and VSA and its mechanisms in thermoregulation, the firing rates of thermosensitive neurons in POAH of forty-seven unit discharge were recorded by using extracellular microelectrode technique in New Zealand white rabbits. Our results show that the firing rates of the warm-sensitive neurons decreased significantly and those of the cold-sensitive neurons increased in POAH when the pyrogen (IL-1beta) was injected I.C.V. The effects of IL-1beta on firing rates in thermosensitive neurons of POAH were reversed by electrical stimulation of VSA. An arginine vasopressin (AVP) V1 antagonist abolished the regulatory effects of VSA on the firing rates in thermosensitive neurons of POAH evoked by IL-1beta. However, an AVP V2 antagonist had no effects. These data indicated that VSA regulates the activities of the thermosensitive neurons of POAH through AVP V1 but not AVP V2 receptor.

  2. [Securing the use of thermosensitive drugs].

    Science.gov (United States)

    Castel, Camille; Saint-Lorant, Guillaume

    2015-10-01

    The safety of patient care entails complying with the temperature requirements for thermosensitive drugs. Field studies carried out at the CHU de Caen University Hospital have demonstrated that patients and caregivers do not understand the critical aspect of thermosensitive drugs. This observation has led to the development of tools designed to secure the cold chain for thermosensitive drugs and to increase awareness among healthcare professionals. Copyright © 2015 Elsevier Masson SAS. All rights reserved.

  3. The race to the nociceptor: mechanical versus temperature effects in thermal pain of dental neurons

    Science.gov (United States)

    Lin, Min; Liu, Fusheng; Liu, Shaobao; Ji, Changchun; Li, Ang; Lu, Tian Jian; Xu, Feng

    2017-04-01

    The sensing of hot and cold stimuli by dental neurons differs in several fundamental ways. These sensations have been characterized quantitatively through the measured time course of neural discharge signals that result from hot or cold stimuli applied to the teeth of animal models. Although various hypotheses have been proposed to explain the underlying mechanism, the ability to test competing hypotheses against experimental recorded data using biophysical models has been hindered by limitations in our understanding of the specific ion channels involved in nociception of dental neurons. Here we apply recent advances in established biophysical models to test the competing hypotheses. We show that a sharp shooting pain sensation experienced shortly following cold stimulation cannot be attributed to the activation of thermosensitive ion channels, thereby falsifying the so-called neuronal hypothesis, which states that rapidly transduced sensations of coldness are related to thermosensitive ion channels. Our results support a central role of mechanosensitive ion channels and the associated hydrodynamic hypothesis. In addition to the hydrodynamic hypothesis, we also demonstrate that the long time delay of dental neuron responses after hot stimulation could be attributed to the neuronal hypothesis—that a relatively long time is required for the temperature around nociceptors to reach some threshold. The results are useful as a model of how multiphysical phenomena can be combined to provide mechanistic insight into different mechanisms underlying pain sensations.

  4. Effects of cold temperatures on the excitability of rat trigeminal ganglion neurons that are not for cold-sensing

    Science.gov (United States)

    Kanda, Hirosato; Gu, Jianguo G.

    2016-01-01

    Except a small population of primary afferent neurons for sensing cold to generate the sensations of innocuous and noxious cold, it is generally believed that cold temperatures suppress the excitability of other primary afferent neurons that are not for cold-sensing. These not-for-cold-sensing neurons include the majority of non-nociceptive and nociceptive afferent neurons. In the present study we have found that not-for-cold-sensing neurons of rat trigeminal ganglia (TG) change their excitability in several ways at cooling temperatures. In nearly 70% of not-for-cold-sensing TG neurons, the cooling temperature of 15°C increases their membrane excitability. We regard these neurons as cold-active neurons. For the remaining 30% of not-for-cold-sensing TG neurons, the cooling temperature of 15°C either has no effect (regarded as cold-ineffective neurons) or suppress (regarded as cold-suppressive neurons) their membrane excitability. For cold-active neurons, the cold temperature of 15°C increases their excitability as is evidenced by the increases in action potential (AP) firing numbers and/or reduction of AP rheobase when these neurons are depolarized electrically. The cold temperature of 15°C significantly inhibits M-currents and increases membrane input resistance of cold-active neurons. Retigabine, an M-current activator, abolishes the effect of cold temperatures on AP firing but not the effect of cold temperature on AP rheobase levels. The inhibition of M-currents and the increases of membrane input resistance are likely two mechanisms by which cooling temperatures increase the excitability of not-for-cold-sensing TG neurons. PMID:26709732

  5. The molecular and cellular basis of cold sensation.

    Science.gov (United States)

    McKemy, David D

    2013-02-20

    Of somatosensory modalities, cold is one of the more ambiguous percepts, evoking the pleasant sensation of cooling, the stinging bite of cold pain, and welcome relief from chronic pain. Moreover, unlike the precipitous thermal thresholds for heat activation of thermosensitive afferent neurons, thresholds for cold fibers are across a range of cool to cold temperatures that spans over 30 °C. Until recently, how cold produces this myriad of biological effects has been poorly studied, yet new advances in our understanding of cold mechanisms may portend a better understanding of sensory perception as well as provide novel therapeutic approaches. Chief among these was the identification of a number of ion channels that either serve as the initial detectors of cold as a stimulus in the peripheral nervous system, or are part of rather sophisticated differential expression patterns of channels that conduct electrical signals, thereby endowing select neurons with properties that are amenable to electrical signaling in the cold. This review highlights the current understanding of the channels involved in cold transduction as well as presents a hypothetical model to account for the broad range of cold thermal thresholds and distinct functions of cold fibers in perception, pain, and analgesia.

  6. How cold is it? TRPM8 and TRPA1 in the molecular logic of cold sensation

    Directory of Open Access Journals (Sweden)

    McKemy David D

    2005-04-01

    Full Text Available Abstract Recognition of temperature is a critical element of sensory perception and allows us to evaluate both our external and internal environments. In vertebrates, the somatosensory system can discriminate discrete changes in ambient temperature, which activate nerve endings of primary afferent fibers. These thermosensitive nerves can be further segregated into those that detect either innocuous or noxious (painful temperatures; the latter neurons being nociceptors. We now know that thermosensitive afferents express ion channels of the transient receptor potential (TRP family that respond at distinct temperature thresholds, thus establishing the molecular basis for thermosensation. Much is known of those channels mediating the perception of noxious heat; however, those proposed to be involved in cool to noxious cold sensation, TRPM8 and TRPA1, have only recently been described. The former channel is a receptor for menthol, and links the sensations provided by this and other cooling compounds to temperature perception. While TRPM8 almost certainly performs a critical role in cold signaling, its part in nociception is still at issue. The latter channel, TRPA1, is activated by the pungent ingredients in mustard and cinnamon, but has also been postulated to mediate our perception of noxious cold temperatures. However, a number of conflicting reports have suggested that the role of this channel in cold sensation needs to be confirmed. Thus, the molecular logic for the perception of cold-evoked pain remains enigmatic. This review is intended to summarize our current understanding of these cold thermoreceptors, as well as address the current controversy regarding TRPA1 and cold signaling.

  7. Thermo-sensitive nanoparticles for triggered release of siRNA.

    Science.gov (United States)

    Yang, Zheng; Cheng, Qiang; Jiang, Qian; Deng, Liandong; Liang, Zicai; Dong, Anjie

    2015-01-01

    Efficient delivery of small interfering RNA (siRNA) is crucially required for cancer gene therapy. Herein, a thermo-sensitive copolymer with a simple structure, poly (ethylene glycol) methyl ether acrylate-b-poly (N-isopropylacrylamide) (mPEG-b-PNIPAM) was developed. A novel kind of thermo-sensitive nanoparticles (DENPs) was constructed for the cold-shock triggered release of siRNA by double emulsion-solvent evaporation method using mPEG-b-PNIPAM and a cationic lipid, 3β [N-(N', N'-dimethylaminoethane)-carbamoyl] cholesterol [DC-Chol]. DENPs were observed by transmission electron microscopy and dynamical light scattering before and after 'cold shock' treatment. The encapsulation efficiency (EE) of siRNA in DENPs, which was measured by fluorescence spectrophotometer was 96.8% while it was significantly reduced to be 23.2% when DC-Chol was absent. DENPs/siRNA NPs exhibited a thermo-sensitive siRNA release character that the cumulatively released amount of siRNA from cold shock was approximately 2.2 folds higher after 7 days. In vitro luciferase silencing experiments indicated that DENPs showed potent gene silencing efficacy in HeLa-Luc cells (HeLa cells steadily expressed luciferase), which was further enhanced by a cold shock. Furthermore, MTT assay showed that cell viability with DENPs/siRNA up to 200 nM remained above 80%. We also observed that most of siRNA was accumulated in kidney mediated by DENPs instead of liver and spleen in vivo experiments. Thus, DENPs as a cold shock responsive quick release model for siRNA or hydrophilic macromolecules delivery provide a new way to nanocarrier design and clinic therapy.

  8. Effects of cold temperatures on the excitability of rat trigeminal ganglion neurons that are not for cold sensing.

    Science.gov (United States)

    Kanda, Hirosato; Gu, Jianguo G

    2017-05-01

    Aside from a small population of primary afferent neurons for sensing cold, which generate sensations of innocuous and noxious cold, it is generally believed that cold temperatures suppress the excitability of primary afferent neurons not responsible for cold sensing. These not-for-cold-sensing neurons include the majority of non-nociceptive and nociceptive afferent neurons. In this study we have found that the not-for-cold-sensing neurons of rat trigeminal ganglia (TG) change their excitability in several ways at cooling temperatures. In nearly 70% of not-for-cold-sensing TG neurons, a cooling temperature of 15°C increases their membrane excitability. We regard these neurons as cold-active neurons. For the remaining 30% of not-for-cold-sensing TG neurons, the cooling temperature of 15°C either has no effect (cold-ineffective neurons) or suppress their membrane excitability (cold-suppressive neurons). For cold-active neurons, the cold temperature of 15°C increases their excitability as is evidenced by increases in action potential (AP) firing numbers and/or the reduction in AP rheobase when these neurons are depolarized electrically. The cold temperature of 15°C significantly inhibits M-currents and increases membrane input resistance of cold-active neurons. Retigabine, an M-current activator, abolishes the effect of cold temperatures on AP firing, but not the effect of cold temperature on AP rheobase levels. The inhibition of M-currents and the increases of membrane input resistance are likely two mechanisms by which cooling temperatures increase the excitability of not-for-cold-sensing TG neurons. This article is part of the special article series "Pain". © 2015 International Society for Neurochemistry.

  9. The TRPM2 channel: A thermo-sensitive metabolic sensor.

    Science.gov (United States)

    Kashio, Makiko; Tominaga, Makoto

    2017-09-03

    Living organisms continually experience changes in ambient temperature. To detect such temperature changes for adaptive behavioral responses, we evolved the ability to sense temperature. Thermosensitive transient receptor potential (TRP) channels, so-called thermo-TRPs, are involved in many physiologic functions in diverse organisms and constitute important temperature sensors. One of the important roles of thermo-TRPs is detecting ambient temperature in sensory neurons. Importantly, the functional expression of thermo-TRPs is observed not only in sensory neurons but also in tissues and cells that are not exposed to drastic temperature changes, indicating that thermo-TRPs are involved in many physiologic functions within the body's normal temperature range. Among such thermo-TRPs, this review focuses on one thermo-sensitive metabolic sensor in particular, TRPM2, and summarizes recent progress to clarify the regulatory mechanisms and physiologic functions of TRPM2 at body temperature under various metabolic states.

  10. Ionic mechanisms of spinal neuronal cold hypersensitivity in ciguatera.

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    Patel, Ryan; Brice, Nicola L; Lewis, Richard J; Dickenson, Anthony H

    2015-12-01

    Cold hypersensitivity is evident in a range of neuropathies and can evoke sensations of paradoxical burning cold pain. Ciguatoxin poisoning is known to induce a pain syndrome caused by consumption of contaminated tropical fish that can persist for months and include pruritus and cold allodynia; at present no suitable treatment is available. This study examined, for the first time, the neural substrates and molecular components of Pacific ciguatoxin-2-induced cold hypersensitivity. Electrophysiological recordings of dorsal horn lamina V/VI wide dynamic range neurones were made in non-sentient rats. Subcutaneous injection of 10 nm ciguatoxin-2 into the receptive field increased neuronal responses to innocuous and noxious cooling. In addition, neuronal responses to low-threshold but not noxious punctate mechanical stimuli were also elevated. The resultant cold hypersensitivity was not reversed by 6-({2-[2-fluoro-6-(trifluoromethyl)phenoxy]-2-methylpropyl}carbamoyl)pyridine-3-carboxylic acid, an antagonist of transient receptor potential melastatin 8 (TRPM8). Both mechanical and cold hypersensitivity were completely prevented by co-injection with the Nav 1.8 antagonist A803467, whereas the transient receptor potential ankyrin 1 (TRPA1) antagonist A967079 only prevented hypersensitivity to innocuous cooling and partially prevented hypersensitivity to noxious cooling. In naive rats, neither innocuous nor noxious cold-evoked neuronal responses were inhibited by antagonists of Nav 1.8, TRPA1 or TRPM8 alone. Ciguatoxins may confer cold sensitivity to a subpopulation of cold-insensitive Nav 1.8/TRPA1-positive primary afferents, which could underlie the cold allodynia reported in ciguatera. These data expand the understanding of central spinal cold sensitivity under normal conditions and the role of these ion channels in this translational rat model of ciguatoxin-induced hypersensitivity. © 2015 The Authors. European Journal of Neuroscience published by Federation of

  11. Thermo-sensitive TRP channels in peripheral nerve injury: a review of their role in cold intolerance.

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    Kambiz, S; Duraku, L S; Holstege, J C; Hovius, S E R; Ruigrok, T J H; Walbeehm, E T

    2014-05-01

    One of the sensory complications of traumatic peripheral nerve injury is thermal intolerance, which manifests in humans mainly as cold intolerance. It has a major effect on the quality of life, and adequate therapy is not yet available. In order to better understand the pathophysiological background of thermal intolerance, we focus first on the various transient receptor potential (TRP) channels that are involved in temperature sensation, including their presence in peripheral nerves and in keratinocytes. Second, the role of thermo-sensitive TRP channels in cold and heat intolerance is described showing three different mechanisms that contribute to thermal intolerance in the skin: (a) an increased expression of TRP channels on nerve fibres and on keratinocytes, (b) a lower activation threshold of TRP channels and (c) the sprouting of non-injured nerve fibres. Finally, the data that are available on the effects of TRP channel agonists and antagonists and their clinical use are discussed. In conclusion, TRP channels play a major role in temperature sensation and in cold and heat intolerance. Unfortunately, the available pharmaceutical agents that successfully target TRP channels and counteract thermal intolerance are still very limited. Yet, our focus should remain on TRP channels since it is difficult to imagine a reliable treatment for thermal intolerance that will not involve TRP channels. Copyright © 2013 British Association of Plastic, Reconstructive and Aesthetic Surgeons. Published by Elsevier Ltd. All rights reserved.

  12. The TRP Channels Pkd2, NompC, and Trpm Act in Cold-Sensing Neurons to Mediate Unique Aversive Behaviors to Noxious Cold in Drosophila.

    Science.gov (United States)

    Turner, Heather N; Armengol, Kevin; Patel, Atit A; Himmel, Nathaniel J; Sullivan, Luis; Iyer, Srividya Chandramouli; Bhattacharya, Surajit; Iyer, Eswar Prasad R; Landry, Christian; Galko, Michael J; Cox, Daniel N

    2016-12-05

    The basic mechanisms underlying noxious cold perception are not well understood. We developed Drosophila assays for noxious cold responses. Larvae respond to near-freezing temperatures via a mutually exclusive set of singular behaviors-in particular, a full-body contraction (CT). Class III (CIII) multidendritic sensory neurons are specifically activated by cold and optogenetic activation of these neurons elicits CT. Blocking synaptic transmission in CIII neurons inhibits CT. Genetically, the transient receptor potential (TRP) channels Trpm, NompC, and Polycystic kidney disease 2 (Pkd2) are expressed in CIII neurons, where each is required for CT. Misexpression of Pkd2 is sufficient to confer cold responsiveness. The optogenetic activation level of multimodal CIII neurons determines behavioral output, and visualization of neuronal activity supports this conclusion. Coactivation of cold- and heat-responsive sensory neurons suggests that the cold-evoked response circuitry is dominant. Our Drosophila model will enable a sophisticated molecular genetic dissection of cold nociceptive genes and circuits. Copyright © 2016 Elsevier Ltd. All rights reserved.

  13. TRPA1 expression levels and excitability brake by KV channels influence cold sensitivity of TRPA1-expressing neurons.

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    Memon, Tosifa; Chase, Kevin; Leavitt, Lee S; Olivera, Baldomero M; Teichert, Russell W

    2017-06-14

    The molecular sensor of innocuous (painless) cold sensation is well-established to be transient receptor potential cation channel, subfamily M, member 8 (TRPM8). However, the role of transient receptor potential cation channel, subfamily A, member 1 (TRPA1) in noxious (painful) cold sensation has been controversial. We find that TRPA1 channels contribute to the noxious cold sensitivity of mouse somatosensory neurons, independent of TRPM8 channels, and that TRPA1-expressing neurons are largely non-overlapping with TRPM8-expressing neurons in mouse dorsal-root ganglia (DRG). However, relatively few TRPA1-expressing neurons (e.g., responsive to allyl isothiocyanate or AITC, a selective TRPA1 agonist) respond overtly to cold temperature in vitro, unlike TRPM8-expressing neurons, which almost all respond to cold. Using somatosensory neurons from TRPM8-/- mice and subtype-selective blockers of TRPM8 and TRPA1 channels, we demonstrate that responses to cold temperatures from TRPA1-expressing neurons are mediated by TRPA1 channels. We also identify two factors that affect the cold-sensitivity of TRPA1-expressing neurons: (1) cold-sensitive AITC-sensitive neurons express relatively more TRPA1 transcripts than cold-insensitive AITC-sensitive neurons and (2) voltage-gated potassium (K V ) channels attenuate the cold-sensitivity of some TRPA1-expressing neurons. The combination of these two factors, combined with the relatively weak agonist-like activity of cold temperature on TRPA1 channels, partially explains why few TRPA1-expressing neurons respond to cold. Blocking K V channels also reveals another subclass of noxious cold-sensitive DRG neurons that do not express TRPM8 or TRPA1 channels. Altogether, the results of this study provide novel insights into the cold-sensitivity of different subclasses of somatosensory neurons. Copyright © 2017 IBRO. Published by Elsevier Ltd. All rights reserved.

  14. Thermo-sensitive intelligent track membrane

    International Nuclear Information System (INIS)

    Pang Deling; Ren Lihua; Qian Zhilin; Huang Gang; Zhang Jinhua

    1999-01-01

    Using N-isopropylacryl-amide (NIP AAm) thermo-sensitive function material as monomer and nuclear track microporous membrane (NTMM) as baseline material, a thermo-sensitive intelligent track membrane (TsITM) has been prepared by the over-oxidization and pre-irradiation grafting techniques. The TsITM can be used to make a micro-switch controlled by temperature and to adjust particle screening and osmosis. To obtain sub-micron responsive grafted track pores only a very thin thermo-sensitive layer is needed. The TsITM pores are capable of swelling and shrinking rapidly and respond more sensitively to temperature

  15. Ciguatoxins activate specific cold pain pathways to elicit burning pain from cooling

    OpenAIRE

    Vetter, Irina; Touska, Filip; Hess, Andreas; Hinsbey, Rachel; Sattler, Simon; Lampert, Angelika; Sergejeva, Marina; Sharov, Anastasia; Collins, Lindon S; Eberhardt, Mirjam; Engel, Matthias; Cabot, Peter J; Wood, John N; Vlachová, Viktorie; Reeh, Peter W

    2012-01-01

    Ciguatoxins derived from fish lead to cold allodynia in humans, the perception of intense burning pain in response to mild cooling. A novel mouse model of ciguatoxin-induced cold allodynia reveals that ciguatoxin activates the TRPA1 thermosensitive ion channel to mediate pain perception.

  16. The influence of cold temperature on cellular excitability of hippocampal networks.

    Science.gov (United States)

    de la Peña, Elvira; Mälkiä, Annika; Vara, Hugo; Caires, Rebeca; Ballesta, Juan J; Belmonte, Carlos; Viana, Felix

    2012-01-01

    The hippocampus plays an important role in short term memory, learning and spatial navigation. A characteristic feature of the hippocampal region is its expression of different electrical population rhythms and activities during different brain states. Physiological fluctuations in brain temperature affect the activity patterns in hippocampus, but the underlying cellular mechanisms are poorly understood. In this work, we investigated the thermal modulation of hippocampal activity at the cellular network level. Primary cell cultures of mouse E17 hippocampus displayed robust network activation upon light cooling of the extracellular solution from baseline physiological temperatures. The activity generated was dependent on action potential firing and excitatory glutamatergic synaptic transmission. Involvement of thermosensitive channels from the transient receptor potential (TRP) family in network activation by temperature changes was ruled out, whereas pharmacological and immunochemical experiments strongly pointed towards the involvement of temperature-sensitive two-pore-domain potassium channels (K(2P)), TREK/TRAAK family. In hippocampal slices we could show an increase in evoked and spontaneous synaptic activity produced by mild cooling in the physiological range that was prevented by chloroform, a K(2P) channel opener. We propose that cold-induced closure of background TREK/TRAAK family channels increases the excitability of some hippocampal neurons, acting as a temperature-sensitive gate of network activation. Our findings in the hippocampus open the possibility that small temperature variations in the brain in vivo, associated with metabolism or blood flow oscillations, act as a switch mechanism of neuronal activity and determination of firing patterns through regulation of thermosensitive background potassium channel activity.

  17. Two different avian cold-sensitive sensory neurons: Transient receptor potential melastatin 8 (TRPM8)-dependent and -independent activation mechanisms.

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    Yamamoto, A; Takahashi, K; Saito, S; Tominaga, M; Ohta, T

    2016-12-01

    Sensing the ambient temperature is an important function for survival in animals. Some TRP channels play important roles as detectors of temperature and irritating chemicals. There are functional differences of TRP channels among species. TRPM8 in mammals is activated by cooling compounds and cold temperature, but less information is available on the functional role of TRPM8 in avian species. Here we investigated the pharmacological properties and thermal sensitivities of chicken TRPM8 (cTRPM8) and cold-sensitive mechanisms in avian sensory neurons. In heterologously expressed cTRPM8, menthol and its derivative, WS-12 elicited [Ca 2+ ] i increases, but icilin did not. In chicken sensory neurons, icilin increased [Ca 2+ ] i, in a TRPA1-dependent manner. Icilin selectively stimulated heterologously expressed chicken TRPA1 (cTRPA1). Similar to mammalian orthologue, cTRPM8 was activated by cold. Both heterologous and endogenous expressed cTRPM8 were sensitive to mammalian TRPM8 antagonists. There are two types of cold-sensitive cells regarding menthol sensitivity in chicken sensory neurons. The temperature threshold of menthol-insensitive neurons was significantly lower than that of menthol-sensitive ones. The population of menthol-insensitive neurons was large in chicken but almost little in mammals. The cold-induced [Ca 2+ ] i increases were not abolished by the external Ca 2+ removal or by blockades of PLC-IP 3 pathways and ryanodine channels. The cold stimulation failed to evoke [Ca 2+ ] i increases after intracellular Ca 2+ store-depletion. These results indicate that cTRPM8 acts as a cold-sensor similar to mammals. It is noteworthy that TRPM8-independent cold-sensitive neurons are abundant in chicken sensory neurons. Our results suggest that most of the cold-induced [Ca 2+ ] i increases are mediated via Ca 2+ release from intracellular stores and that these mechanisms may be specific to avian species. Copyright © 2016 Elsevier Ltd. All rights reserved.

  18. Effects of antagonists and heat on TRPM8 channel currents in dorsal root ganglion neuron activated by nociceptive cold stress and menthol.

    Science.gov (United States)

    Naziroğlu, Mustafa; Ozgül, Cemil

    2012-02-01

    Transient receptor potential ion channel melastatin subtype 8 (TRPM8) is activated by cold temperature and cooling agents, such as menthol and icilin. Compounds containing peppermint are reported to reduce symptoms of environmental cold stress such as cold allodynia in dorsal root ganglion (DRG) neuron; however, the underlying mechanisms of action are unclear. We tested the effects of physiological heat (37°C), anthralic acid (ACA and 0.025 mM), 2-aminoethyl diphenylborinate (2-APB and 0.05) on noxious cold (10°C) and menthol (0.1 mM)-induced TRPM8 cation channel currents in the DRG neurons of rats. DRG neurons were freshly isolated from rats. In whole-cell patch clamp experiments, TRPM8 currents were consistently induced by noxious cold or menthol. TRPM8 channels current densities of the neurons were higher in cold and menthol groups than in control. When the physiological heat is introduced by chamber TRPM8 channel currents were inhibited by the heat. Noxious cold-induced Ca(2+) gates were blocked by the ACA although menthol-induced TRPM8 currents were not blocked by ACA and 2-APB. In conclusion, the results suggested that activation of TRPM8 either by menthol or nociceptive cold can activate TRPM8 channels although we observed the protective role of heat, ACA and 2-APB through a TRPM8 channel in nociceptive cold-activated DRG neurons. Since cold allodynia is a common feature of neuropathic pain and diseases of sensory neuron, our findings are relevant to the etiology of neuropathology in DRG neurons.

  19. Scraping through the ice: uncovering the role of TRPM8 in cold transduction

    Science.gov (United States)

    McCoy, Daniel D.; Knowlton, Wendy M.

    2011-01-01

    The proper detection of environmental temperatures is essential for the optimal growth and survival of organisms of all shapes and phyla, yet only recently have the molecular mechanisms for temperature sensing been elucidated. The discovery of temperature-sensitive ion channels of the transient receptor potential (TRP) superfamily has been pivotal in explaining how temperatures are sensed in vivo, and here we will focus on the lone member of this cohort, TRPM8, which has been unequivocally shown to be cold sensitive. TRPM8 is expressed in somatosensory neurons that innervate peripheral tissues such as the skin and oral cavity, and recent genetic evidence has shown it to be the principal transducer of cool and cold stimuli. It is remarkable that this one channel, unlike other thermosensitive TRP channels, is associated with both innocuous and noxious temperature transduction, as well as cold hypersensitivity during injury and, paradoxically, cold-mediated analgesia. With ongoing research, the field is getting closer to answering a number of fundamental questions regarding this channel, including the cellular mechanisms of TRPM8 modulation, the molecular context of TRPM8 expression, as well as the full extent of the role of TRPM8 in cold signaling in vivo. These findings will further our understanding of basic thermotransduction and sensory coding, and may have important implications for treatments for acute and chronic pain. PMID:21411765

  20. Selective enrichment and separation of phosphotyrosine peptides by thermosensitive molecularly imprinted polymers.

    Science.gov (United States)

    Yang, Xiaoqing; Xia, Yan

    2016-01-01

    Novel thermosensitive molecularly imprinted polymers were successfully prepared using the epitope imprinting approach in the presence of the mimic template phenylphosphonic acid, the functional monomer vinylphosphonic acid-Ti(4+) , the temperature-sensitive monomer N-isopropylacrylamide and the crosslinker N,N'-methylenebisacrylamide. The ratio of the template/thermosensitive monomers/crosslinker was optimized, and when the ratio was 2:2:1, the prepared thermosensitive molecularly imprinted polymers had the highest imprinting factor. The synthetic thermosensitive molecularly imprinted polymers were characterized by Fourier transform infrared spectroscopy to reveal the combination and elution processes of the template. Then, the adsorption capacity and thermosensitivity was measured. When the temperature was 28°C, the imprinting factor was the highest. The selectivity and adsorption capacity of the thermosensitive molecularly imprinted polymers for phosphotyrosine peptides from a mixture of three tailor-made peptides were measured by high-performance liquid chromatography. The results showed that the thermosensitive molecularly imprinted polymers have good selectivity for phosphotyrosine peptides. Finally, the imprinted hydrogels were applied to specifically adsorb phosphotyrosine peptides from a sample mixture containing phosphotyrosine and a tryptic digest of β-casein, which demonstrated high selectivity. After four rebinding cycles, 78.9% adsorption efficiency was still retained. © 2015 WILEY-VCH Verlag GmbH & Co. KGaA, Weinheim.

  1. Noise and Synchronization Analysis of the Cold-Receptor Neuronal Network Model

    Directory of Open Access Journals (Sweden)

    Ying Du

    2014-01-01

    Full Text Available This paper analyzes the dynamics of the cold receptor neural network model. First, it examines noise effects on neuronal stimulus in the model. From ISI plots, it is shown that there are considerable differences between purely deterministic simulations and noisy ones. The ISI-distance is used to measure the noise effects on spike trains quantitatively. It is found that spike trains observed in neural models can be more strongly affected by noise for different temperatures in some aspects; meanwhile, spike train has greater variability with the noise intensity increasing. The synchronization of neuronal network with different connectivity patterns is also studied. It is shown that chaotic and high period patterns are more difficult to get complete synchronization than the situation in single spike and low period patterns. The neuronal network will exhibit various patterns of firing synchronization by varying some key parameters such as the coupling strength. Different types of firing synchronization are diagnosed by a correlation coefficient and the ISI-distance method. The simulations show that the synchronization status of neurons is related to the network connectivity patterns.

  2. Acute cold hypersensitivity characteristically induced by oxaliplatin is caused by the enhanced responsiveness of TRPA1 in mice

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    Zhao Meng

    2012-07-01

    Full Text Available Abstract Background Oxaliplatin, a platinum-based chemotherapeutic agent, causes an unusual acute peripheral neuropathy. Oxaliplatin-induced acute peripheral neuropathy appears in almost all patients rapidly after infusion, and is triggered or exacerbated by cold, while its mechanisms are poorly understood. In this study, the involvement of thermosensitive transient receptor potential channels (TRPA1, TRPM8 and TRPV1 in oxaliplatin-induced acute hypersensitivity was investigated in mice. Results A single intraperitoneal administration of oxaliplatin (1–10 mg/kg induced cold but not mechanical hypersensitivity within 2 h in a dose-dependent manner. Infusion of the oxaliplatin metabolite, oxalate (1.7 mg/kg, also induced acute cold hypersensitivity, while another platinum-based chemotherapeutic agent, cisplatin (5 mg/kg, or the non-platinum-containing chemotherapeutic agent, paclitaxel (6 mg/kg failed to induce mechanical or cold hypersensitivity. The oxaliplatin-induced acute cold hypersensitivity was abolished by the TRPA1 antagonist HC-030031 (100 mg/kg and by TRPA1 deficiency. The nocifensive behaviors evoked by intraplantar injections of allyl-isothiocyanate (AITC; TRPA1 agonist were significantly enhanced in mice treated for 2 h with oxaliplatin (1–10 mg/kg in a dose-dependent manner, while capsaicin (TRPV1 agonist-evoked nocifensive behaviors were not affected. Menthol (TRPM8/TRPA1 agonist-evoked nocifensive-like behaviors were also enhanced by oxaliplatin pretreatment, which were inhibited by TRPA1 deficiency. Similarly, oxalate enhanced, but neither cisplatin nor paclitaxel affected AITC-evoked nocifensive behaviors. Pretreatment of cultured mouse dorsal root ganglia (DRG neurons with oxaliplatin (30–300 μM for 1, 2, or 4 h significantly increased the number of AITC-sensitive neurons in a concentration-dependent manner whereas there was no change in the number of menthol- or capsaicin-sensitive neurons

  3. Cold-Adapted Enzymes

    Science.gov (United States)

    Georlette, D.; Bentahir, M.; Claverie, P.; Collins, T.; D'amico, S.; Delille, D.; Feller, G.; Gratia, E.; Hoyoux, A.; Lonhienne, T.; Meuwis, M.-a.; Zecchinon, L.; Gerday, Ch.

    In the last few years, increased attention has been focused on enzymes produced by cold-adapted micro-organisms. It has emerged that psychrophilic enzymes represent an extremely powerful tool in both protein folding investigations and for biotechnological purposes. Such enzymes are characterised by an increased thermosensitivity and, most of them, by a higher catalytic efficiency at low and moderate temperatures, when compared to their mesophilic counterparts. The high thermosensitivity probably originates from an increased flexibility of either a selected area of the molecular edifice or the overall protein structure, providing enhanced abilities to undergo conformational changes during catalysis at low temperatures. Structure modelling and recent crystallographic data have allowed to elucidate the structural parameters that could be involved in this higher resilience. It was demonstrated that each psychrophilic enzyme adopts its own adaptive strategy. It appears, moreover, that there is a continuum in the strategy of protein adaptation to temperature, as the previously mentioned structural parameters are implicated in the stability of thermophilic proteins. Additional 3D crystal structures, site-directed and random mutagenesis experiments should now be undertaken to further investigate the stability-flexibility-activity relationship.

  4. Thermosensitive polymer-grafted iron oxide nanoparticles studied by in situ dynamic light backscattering under magnetic hyperthermia

    Science.gov (United States)

    Hemery, Gauvin; Garanger, Elisabeth; Lecommandoux, Sébastien; Wong, Andrew D.; Gillies, Elizabeth R.; Pedrono, Boris; Bayle, Thomas; Jacob, David; Sandre, Olivier

    2015-12-01

    Thermometry at the nanoscale is an emerging area fostered by intensive research on nanoparticles (NPs) that are capable of converting electromagnetic waves into heat. Recent results suggest that stationary gradients can be maintained between the surface of NPs and the bulk solvent, a phenomenon sometimes referred to as ‘cold hyperthermia’. However, the measurement of such highly localized temperatures is particularly challenging. We describe here a new approach to probing the temperature at the surface of iron oxide NPs and enhancing the understanding of this phenomenon. This approach involves the grafting of thermosensitive polymer chains to the NP surface followed by the measurement of macroscopic properties of the resulting NP suspension and comparison to a calibration curve built up by macroscopic heating. Superparamagnetic iron oxide NPs were prepared by the coprecipitation of ferrous and ferric salts and functionalized with amines, then azides using a sol-gel route followed by a dehydrative coupling reaction. Thermosensitive poly[2-(dimethylamino)ethyl methacrylate] (PDMAEMA) with an alkyne end-group was synthesized by controlled radical polymerization and was grafted using a copper assisted azide-alkyne cycloaddition reaction. Measurement of the colloidal properties by dynamic light scattering (DLS) indicated that the thermosensitive NPs exhibited changes in their Zeta potential and hydrodynamic diameter as a function of pH and temperature due to the grafted PDMAEMA chains. These changes were accompanied by changes in the relaxivities of the NPs, suggesting application as thermosensitive contrast agents for magnetic resonance imaging (MRI). In addition, a new fibre-based backscattering setup enabled positioning of the DLS remote-head as close as possible to the coil of a magnetic heating inductor to afford in situ probing of the backscattered light intensity, hydrodynamic diameter, and temperature. This approach provides a promising platform for

  5. Representation of thermal information in the antennal lobe of leaf-cutting ants

    Directory of Open Access Journals (Sweden)

    Markus eRuchty

    2010-11-01

    Full Text Available Insects are equipped with various types of antennal sensilla, which house thermosensitive neurons adapted to receive different parameters of the thermal environment for a variety of temperature-guided behaviors. In the leaf-cutting ant Atta vollenweideri, the physiology and the morphology of the thermosensitive sensillum coeloconicum (Sc has been thoroughly investigated. However, the central projections of its receptor neurons are unknown. Here we selectively stained the three neurons found in single Sc and tracked their axons into the brain of Atta vollenweideri workers. Each of the three axons terminates in a single glomerulus of the antennal lobe (Sc-glomeruli. Two of the innervated glomeruli are adjacent to each other and are located laterally, while the third one is clearly separated and located medially in the antennal lobe. Using two-photon Ca2+ imaging of antennal lobe projection neurons, we studied where in the antennal lobe thermal information is represented. In the 11 investigated antennal lobes, we found up to 10 different glomeruli in a single specimen responding to temperature stimulation. Both, warm- and cold-sensitive glomeruli could be identified. The thermosensitive glomeruli were mainly located in the medial part of the antennal lobe. Based on the general representation of thermal information in the antennal lobe and functional data on the Sc-glomeruli we conclude that temperature stimuli received by Sc are processed in the medial of the three target glomeruli. The present study reveals an important role of the antennal lobe in temperature processing and links a specific thermosensitive neuron to its central target glomerulus.

  6. Investigation of particle accumulation, chemosensitivity and thermosensitivity for effective solid tumor therapy using thermosensitive liposomes and hyperthermia

    NARCIS (Netherlands)

    W.J.M. Lokerse (Wouter); M. Bolkestein (Michiel); T.L.M. ten Hagen (Timo); M. de Jong (Marcel); A.M.M. Eggermont (Alexander); Grüll, H. (Holger); G.A. Koning (Gerben)

    2016-01-01

    textabstractDoxorubicin (Dox) loaded thermosensitive liposomes (TSLs) have shown promising results for hyperthermia-induced local drug delivery to solid tumors. Typically, the tumor is heated to hyperthermic temperatures (41-42 °C), which induced intravascular drug release from TSLs within the tumor

  7. The Nav1.9 Channel Is a Key Determinant of Cold Pain Sensation and Cold Allodynia

    Directory of Open Access Journals (Sweden)

    Stéphane Lolignier

    2015-05-01

    Full Text Available Cold-triggered pain is essential to avoid prolonged exposure to harmfully low temperatures. However, the molecular basis of noxious cold sensing in mammals is still not completely understood. Here, we show that the voltage-gated Nav1.9 sodium channel is important for the perception of pain in response to noxious cold. Nav1.9 activity is upregulated in a subpopulation of damage-sensing sensory neurons responding to cooling, which allows the channel to amplify subthreshold depolarizations generated by the activation of cold transducers. Consequently, cold-triggered firing is impaired in Nav1.9−/− neurons, and Nav1.9 null mice and knockdown rats show increased cold pain thresholds. Disrupting Nav1.9 expression in rodents also alleviates cold pain hypersensitivity induced by the antineoplastic agent oxaliplatin. We conclude that Nav1.9 acts as a subthreshold amplifier in cold-sensitive nociceptive neurons and is required for the perception of cold pain under normal and pathological conditions.

  8. Fabricating continuous electroconductive polyacrylonitrile fibers with thermosensitive property via wet-spinning

    Science.gov (United States)

    Liu, Wanwan; Jin, Yang; Wang, Yangyi; Ge, Mingqiao; Gao, Qiang

    2017-12-01

    In this work, conductive polyacrylonitrile (PAN) composite fiber with thermosensitive property was successfully prepared via wet-spinning. Thermochromic pigment (TCP) microsphere capsules were applied to manufacture color-changing fibers. Meanwhile, light-colored conductive whiskers (ATO@TiO2) were employed to endow polyacrylonitrile fibers with conductivity without prejudicing their thermosensitive property. Interestingly, unlike other conductive fibers in dark color, this kind of conductive composite fiber can be dyed by thermosensitive pigment. The obtained composite fiber containing 20 vol% ATO@TiO2 whiskers shows a resistivity of 105 Ω · cm and could generate heat by Joule heating when being applied under a certain voltage. The composite fiber shows a red color at room temperature, while the color of the composite fiber fades gradually and finally becomes white as temperature rise. This simple and cost-effective approach is expected to inspire more research into the applications of multifunctional conductive fibers.

  9. Thermosensitive liposomal drug delivery systems: state of the art review

    Directory of Open Access Journals (Sweden)

    Kneidl B

    2014-09-01

    Full Text Available Barbara Kneidl,1,2 Michael Peller,3 Gerhard Winter,2 Lars H Lindner,1 Martin Hossann11Department of Internal Medicine III, University Hospital Munich, 2Department of Pharmacy, Pharmaceutical Technology and Biopharmaceutics, 3Institute for Clinical Radiology, University Hospital Munich, Ludwig-Maximilians University, Munich, GermanyAbstract: Thermosensitive liposomes are a promising tool for external targeting of drugs to solid tumors when used in combination with local hyperthermia or high intensity focused ultrasound. In vivo results have demonstrated strong evidence that external targeting is superior over passive targeting achieved by highly stable long-circulating drug formulations like PEGylated liposomal doxorubicin. Up to March 2014, the Web of Science listed 371 original papers in this field, with 45 in 2013 alone. Several formulations have been developed since 1978, with lysolipid-containing, low temperature-sensitive liposomes currently under clinical investigation. This review summarizes the historical development and effects of particular phospholipids and surfactants on the biophysical properties and in vivo efficacy of thermosensitive liposome formulations. Further, treatment strategies for solid tumors are discussed. Here we focus on temperature-triggered intravascular and interstitial drug release. Drug delivery guided by magnetic resonance imaging further adds the possibility of performing online monitoring of a heating focus to calculate locally released drug concentrations and to externally control drug release by steering the heating volume and power. The combination of external targeting with thermosensitive liposomes and magnetic resonance-guided drug delivery will be the unique characteristic of this nanotechnology approach in medicine.Keywords: thermosensitive liposomes, phosphatidyloligoglycerol, hyperthermia, high intensity focused ultrasound, drug delivery, drug targeting

  10. The Nav1.9 channel is a key determinant of cold pain sensation and cold allodynia.

    Science.gov (United States)

    Lolignier, Stéphane; Bonnet, Caroline; Gaudioso, Christelle; Noël, Jacques; Ruel, Jérôme; Amsalem, Muriel; Ferrier, Jérémy; Rodat-Despoix, Lise; Bouvier, Valentine; Aissouni, Youssef; Prival, Laetitia; Chapuy, Eric; Padilla, Françoise; Eschalier, Alain; Delmas, Patrick; Busserolles, Jérôme

    2015-05-19

    Cold-triggered pain is essential to avoid prolonged exposure to harmfully low temperatures. However, the molecular basis of noxious cold sensing in mammals is still not completely understood. Here, we show that the voltage-gated Nav1.9 sodium channel is important for the perception of pain in response to noxious cold. Nav1.9 activity is upregulated in a subpopulation of damage-sensing sensory neurons responding to cooling, which allows the channel to amplify subthreshold depolarizations generated by the activation of cold transducers. Consequently, cold-triggered firing is impaired in Nav1.9(-/-) neurons, and Nav1.9 null mice and knockdown rats show increased cold pain thresholds. Disrupting Nav1.9 expression in rodents also alleviates cold pain hypersensitivity induced by the antineoplastic agent oxaliplatin. We conclude that Nav1.9 acts as a subthreshold amplifier in cold-sensitive nociceptive neurons and is required for the perception of cold pain under normal and pathological conditions. Copyright © 2015 The Authors. Published by Elsevier Inc. All rights reserved.

  11. Thermosensitive liposomes entrapping iron oxide nanoparticles for controllable drug release

    International Nuclear Information System (INIS)

    Tai, L-A; Wang, Y-C; Wang, Y-J; Yang, C-S; Tsai, P-J; Lo, L-W

    2009-01-01

    Iron oxide nanoparticles can serve as a heating source upon alternative magnetic field (AMF) exposure. Iron oxide nanoparticles can be mixed with thermosensitive nanovehicles for hyperthermia-induced drug release, yet such a design and mechanism may not be suitable for controllable drug release applications in which the tissues are susceptible to environmental temperature change such as brain tissue. In the present study, iron oxide nanoparticles were entrapped inside of thermosensitive liposomes for AMF-induced drug release while the environmental temperature was maintained at a constant level. Carboxyfluorescein was co-entrapped with the iron oxide nanoparticles in the liposomes as a model compound for monitoring drug release and environmental temperature was maintained with a water circulator jacket. These experiments have been successfully performed in solution, in phantom and in anesthetized animals. Furthermore, the thermosensitive liposomes were administered into rat forearm skeletal muscle, and the release of carboxylfluorescein triggered by the external alternative magnetic field was monitored by an implanted microdialysis perfusion probe with an on-line laser-induced fluorescence detector. In the future such a device could be applied to simultaneous magnetic resonance imaging and non-invasive drug release in temperature-sensitive applications.

  12. Thermosensitive shutter for radioactive source housing

    International Nuclear Information System (INIS)

    Fullagar, H.

    1986-01-01

    A shutter apparatus for a radioactive source housing comprises a movable member and a thermosensitive releasing means operative normally to hold the movable member in an open position but to release the movable member to move to a position closing the housing to contain the source when the temperature exceeds a predetermined value, for example as a result of fire. (author)

  13. Diversity in the Neural Circuitry of Cold Sensing Revealed by Genetic Axonal Labeling of Transient Receptor Potential Melastatin 8 Neurons

    OpenAIRE

    Takashima, Yoshio; Daniels, Richard L.; Knowlton, Wendy; Teng, James; Liman, Emily R.; McKemy, David D.

    2007-01-01

    Sensory nerves detect an extensive array of somatosensory stimuli, including environmental temperatures. Despite activating only a small cohort of sensory neurons, cold temperatures generate a variety of distinct sensations that range from pleasantly cool to painfully aching, prickling, and burning. Psychophysical and functional data show that cold responses are mediated by both C- and Aδ-fibers with separate peripheral receptive zones, each of which likely provides one or more of these disti...

  14. Pharmacokinetics, Tissue Distribution and Therapeutic Effect of Cationic Thermosensitive Liposomal Doxorubicin Upon Mild Hyperthermia

    OpenAIRE

    Dicheva, Bilyana M.; Seynhaeve, Ann L. B.; Soulie, Thomas; Eggermont, Alexander M. M.; ten Hagen, Timo L. M.; Koning, Gerben A.

    2015-01-01

    textabstractPurpose: To evaluate pharmacokinetic profile, biodistribution and therapeutic effect of cationic thermosensitive liposomes (CTSL) encapsulating doxorubicin (Dox) upon mild hyperthermia (HT). Methods: Non-targeted thermosensitive liposomes (TSL) and CTSL were developed, loaded with Dox and characterized. Blood kinetics and biodistribution of Dox-TSL and Dox-CTSL were followed in B16BL6 tumor bearing mice upon normothermia (NT) or initial hyperthermia conditions. Efficacy study in B...

  15. Irinotecan-encapsulated double-reverse thermosensitive nanocarrier system for rectal administration.

    Science.gov (United States)

    Din, Fakhar Ud; Choi, Ju Yeon; Kim, Dong Wuk; Mustapha, Omer; Kim, Dong Shik; Thapa, Raj Kumar; Ku, Sae Kwang; Youn, Yu Seok; Oh, Kyung Taek; Yong, Chul Soon; Kim, Jong Oh; Choi, Han-Gon

    2017-11-01

    Intravenously administered for the treatment of rectum cancer, irinotecan produces severe side effects due to very high plasma concentrations. A novel irinotecan-encapsulated double reverse thermosensitive nanocarrier system (DRTN) for rectal administration was developed as an alternative. The DRTN was fabricated by dispersing the thermosensitive irinotecan-encapsulated solid lipid nanoparticles (SLN) in the thermosensitive poloxamer solution. Its gel properties, pharmacokinetics, morphology, anticancer activity and immunohistopathology were assessed after its rectal administration to rats and tumor-bearing mice. In the DRTN, the solid form of the SLN and the liquid form of the poloxamer solution persisted at 25 °C; the former melted to liquid, and the latter altered to gel at 36.5 °C. The DRTN was easily administered to the anus, gelling rapidly and strongly after rectal administration. Compared to the conventional hydrogel and intravenously administered solution, it retarded dissolution and initial plasma concentration. The DRTN gave sustained release and nearly constant plasma concentrations of irinotecan at 1-3 h in rats, resulting in improved anticancer activity. It induced no damage to the rat rectum and no body weight loss in tumor-bearing mice. Thus, this irinotecan-encapsulated DRTN associated with a reduced burst effect, lack of toxicity and excellent antitumor efficacy would be strongly recommended as a rectal pharmaceutical product alternative to commercial intravenous injection in the treatment of rectum and colon cancer.

  16. Thermosensitive PLA based nanodispersion for targeting brain tumor via intranasal route

    International Nuclear Information System (INIS)

    Jain, Darshana S.; Bajaj, Amrita N.; Athawale, Rajani B.; Shikhande, Shruti S.; Pandey, Abhijeet; Goel, Peeyush N.; Gude, Rajiv P.; Patil, Satish; Raut, Preeti

    2016-01-01

    Delivery of drugs to the brain via nasal route has been studied by many researchers. However, low residence time, mucociliary clearance and enzymatically active environment of nasal cavity pose many challenges to successful nasal delivery of drugs. We aim to deliver methotrexate by designing thermosensitive nanodispersion exhibiting enhanced residence time in nasal cavity and bypassing the blood brain barrier (BBB). PLA nanoparticles were developed using solvent evaporation technique. The developed nanoparticles were further dispersed in prepared thermosensitive vehicle of poloxamer 188 and Carbopol 934 to impart the property of increased residence time. The formulated nanoparticles demonstrated no interaction with the simulated nasal fluids (SNF), mucin, serum proteins and erythrocytes which demonstrate the safety of developed formulation for nasal administration. The penetration property of nanoparticles though the nasal mucosa was higher than the pure drug due to low mucociliary clearance. The developed nanoparticles diffused though the membrane pores and rapidly distributed into the brain portions compared to the pure drug. There was detectable and quantifiable amount of drug seen in the brain as demonstrated by in vivo brain distribution studies with considerably low amount of drug deposition in the lungs. The pharmacokinetic parameters demonstrated the enhancement in circulation half life, area under curve (AUC) and Cmax of the drug when administered intranasal in encapsulated form. Thus, the thermosensitive nanodispersions are surely promising delivery systems for delivering anticancer agents though the nasal route for potential treatment of brain tumors. - Highlights: • The present investigation explores intra-nasal route as potential route for targeting brain tumor. • Thermosensitive nanodispersion has been formulated for enhancing nasal residence time. • PLA nanoparticles enhance penetration into the brain owing to hydrophobic nature and small size

  17. Thermosensitive PLA based nanodispersion for targeting brain tumor via intranasal route

    Energy Technology Data Exchange (ETDEWEB)

    Jain, Darshana S., E-mail: darshanaj_cup@yahoo.com [C.U. Shah College of Pharmacy, S.N.D.T Women' s University, Juhu Tara Road, Santacruz (West), Mumbai 400 049 (India); Bajaj, Amrita N. [C.U. Shah College of Pharmacy, S.N.D.T Women' s University, Juhu Tara Road, Santacruz (West), Mumbai 400 049 (India); Athawale, Rajani B., E-mail: rajani.athawale@gmail.com [C.U. Shah College of Pharmacy, S.N.D.T Women' s University, Juhu Tara Road, Santacruz (West), Mumbai 400 049 (India); Shikhande, Shruti S. [C.U. Shah College of Pharmacy, S.N.D.T Women' s University, Juhu Tara Road, Santacruz (West), Mumbai 400 049 (India); Pandey, Abhijeet [H. R Patel Institute of Pharmaceutical Education and Research, Shirpur, Maharashtra (India); Goel, Peeyush N.; Gude, Rajiv P. [Gude Lab, Advanced Centre for Treatment, Research & Education in Cancer (ACTREC), Tata Memorial Centre, Kharghar, Navi Mumbai 410 210 (India); Patil, Satish; Raut, Preeti [Cipla Pvt. Ltd., Vikhroli (West), Mumbai (India)

    2016-06-01

    Delivery of drugs to the brain via nasal route has been studied by many researchers. However, low residence time, mucociliary clearance and enzymatically active environment of nasal cavity pose many challenges to successful nasal delivery of drugs. We aim to deliver methotrexate by designing thermosensitive nanodispersion exhibiting enhanced residence time in nasal cavity and bypassing the blood brain barrier (BBB). PLA nanoparticles were developed using solvent evaporation technique. The developed nanoparticles were further dispersed in prepared thermosensitive vehicle of poloxamer 188 and Carbopol 934 to impart the property of increased residence time. The formulated nanoparticles demonstrated no interaction with the simulated nasal fluids (SNF), mucin, serum proteins and erythrocytes which demonstrate the safety of developed formulation for nasal administration. The penetration property of nanoparticles though the nasal mucosa was higher than the pure drug due to low mucociliary clearance. The developed nanoparticles diffused though the membrane pores and rapidly distributed into the brain portions compared to the pure drug. There was detectable and quantifiable amount of drug seen in the brain as demonstrated by in vivo brain distribution studies with considerably low amount of drug deposition in the lungs. The pharmacokinetic parameters demonstrated the enhancement in circulation half life, area under curve (AUC) and Cmax of the drug when administered intranasal in encapsulated form. Thus, the thermosensitive nanodispersions are surely promising delivery systems for delivering anticancer agents though the nasal route for potential treatment of brain tumors. - Highlights: • The present investigation explores intra-nasal route as potential route for targeting brain tumor. • Thermosensitive nanodispersion has been formulated for enhancing nasal residence time. • PLA nanoparticles enhance penetration into the brain owing to hydrophobic nature and small size

  18. TRPA1 contributes to capsaicin-induced facial cold hyperalgesia in rats.

    Science.gov (United States)

    Honda, Kuniya; Shinoda, Masamichi; Furukawa, Akihiko; Kita, Kozue; Noma, Noboru; Iwata, Koichi

    2014-12-01

    Orofacial cold hyperalgesia is known to cause severe persistent pain in the face following trigeminal nerve injury or inflammation, and transient receptor potential (TRP) vanilloid 1 (TRPV1) and TRP ankylin 1 (TRPA1) are thought to be involved in cold hyperalgesia. However, how these two receptors are involved in cold hyperalgesia is not fully understood. To clarify the mechanisms underlying facial cold hyperalgesia, nocifensive behaviors to cold stimulation, the expression of TRPV1 and TRPA1 in trigeminal ganglion (TG) neurons, and TG neuronal excitability to cold stimulation following facial capsaicin injection were examined in rats. The head-withdrawal reflex threshold (HWRT) to cold stimulation of the lateral facial skin was significantly decreased following facial capsaicin injection. This reduction of HWRT was significantly recovered following local injection of TRPV1 antagonist as well as TRPA1 antagonist. Approximately 30% of TG neurons innervating the lateral facial skin expressed both TRPV1 and TRPA1, and about 64% of TRPA1-positive neurons also expressed TRPV1. The TG neuronal excitability to noxious cold stimulation was significantly increased following facial capsaicin injection and this increase was recovered by pretreatment with TRPA1 antagonist. These findings suggest that TRPA1 sensitization via TRPV1 signaling in TG neurons is involved in cold hyperalgesia following facial skin capsaicin injection. © 2014 Eur J Oral Sci.

  19. Flocculation of flotation tailings using thermosensitive polymers

    Directory of Open Access Journals (Sweden)

    Bogacz Wojciech

    2017-09-01

    Full Text Available The key feature of thermosensitive polymers is the reversible transition between the hydrophilic and hydrophopic forms depending on the temperature. Although the main research efforts are focused on their application in different kinds of drug delivery systems, this phenomenon also allows one to precisely control the stability of solid-liquid dispersions. In this paper research on the application of poly(N-isopropylacrylamide copolymers in processing of minerals is presented. In the experiments tailings from flotation plant of one of the coal mines of Jastrzębska Spółka Węglowa S.A. (Poland were used. A laser particle sizer Fritsch Analysette 22 was used in order to determine the Particle Size Distribution (PSD. It was proved that there are some substantial issues associated with the application of thermosensitive polymers in industrial practice which may exclude them from the common application. High salinity of suspension altered the value of Lower Critical Solution Temperature (LCST. Moreover, the co-polymers used in research proved to be efficient flocculating agents without any temperature rise. Finally, the dosage needed to achieve steric stabilization of suspension was greatly beyond economic justification.

  20. Heparin release from thermosensitive polymer coatings: in vivo studies

    NARCIS (Netherlands)

    Gutowska, Anna; Bae, You Han; Jacobs, Harvey; Mohammad, Fazal; Mix, Donald; Feijen, Jan; Kim, Sung Wan

    1995-01-01

    Biomer/poly(N-isopropylacrylamide)/[poly(NiPAAm)] thermosensitive polymer blends were prepared and their application as heparin-releasing polymer coatings for the prevention of surface-induced thrombosis was examined. The advantage of using poly(NiPAAm)-based coatings as heparin-releasing polymers

  1. The influence of increased cross-linker chain length in thermosensitive microspheres on potential sun-protection activity

    OpenAIRE

    Musiał, Witold; Kokol, Vanja; Vončina, Bojana

    2012-01-01

    The sun protection should involve substances with protecting activity against both UVB and UVA radiation. In this research the evaluation of thermosensitive microspheres as potential molecules for sunscreen formulations was approached, using modified Boots star rating system. The microspheres, thermosensitive N-isopropylacrylamide derivatives, have potential protecting activity against UV radiation. The MX and DX microspheres, with ethylene glycol dimethacrylate and diethylene glycol dimethac...

  2. The influence of increased cross-linker chain length in thermosensitive microspheres on potential sun-protection activity.

    Science.gov (United States)

    Musiał, Witold; Kokol, Vanja; Voncina, Bojana

    2010-01-01

    The sun protection should involve substances with protecting activity against both UVB and UVA radiation. In this research the evaluation of thermosensitive microspheres as potential molecules for sunscreen formulations was approached, using modified Boots star rating system. The microspheres, thermosensitive N-isopropylacrylamide derivatives, have potential protecting activity against UV radiation. The MX and DX microspheres, with ethylene glycol dimethacrylate and diethylene glycol dimethacrylate crosslinker respectively, due to theirs thermosensitivity exhibit increase in protecting activity against UV radiation when heated to 45 degrees C. The MX microspheres have higher increase in terms of UV absorbance, comparing to DX microspheres, when heated in the 25 degrees C to 45 degrees C range. Studied microspheres have high potential for application as components of sun-screens used in elevated temperatures.

  3. Clampless anastomosis with an intraluminal thermosensitive gel: first application in reconstructive microsurgery and literature review.

    Science.gov (United States)

    Giessler, G A; Fischborn, G T; Schmidt, A B

    2012-01-01

    Microvascular clamps of various designs provide a bloodless field for a safe anastomosis but can cause intimal lesions, occupy space in confined sites and have a risk of backwalling due to vessel flattening. They are often insufficient in their haemostatic effect in plaque-filled atherosclerotic vessels. A new, CE-certified thermosensitive gel (LeGoo™) clinically proven in cardiovascular surgery allows a clampless microanastomosis technique. We operated on a series of five consecutive patients aged 24-71 years with six flaps for lower-extremity reconstruction using a clampless anastomosis technique with LeGoo™. We transplanted one fabricated chimaeric fibula plus gracilis, three gracilis muscle and one anterolateral thigh (ALT) flap. Pre- and postoperative protocols were similar to a 'standard' procedure with micro-clamps. All flaps survived completely except for a small area on fibula skin island, which was unrelated to gel use. The gel-assisted technique has a quick learning curve, according to this case series. The veins should be sutured first to prevent stasis in the flap. The gel provides circular stenting and gentle distension of the vessels for a safe and blood-free anastomotic site. It is completely dissolved after completion of the anastomosis with cold saline irrigation. Repolymerisation in the periphery will not occur, making it safe for microvascular flap surgery. From the experiences from this series and other specialities, the use of the thermosensitive gel LeGoo™ permits a safe clampless microanastomosis technique minimising mechanical vessel manipulation and compression. This makes it an attractive alternative to micro-clamps, especially for atherosclerotic arteries and confined anastomosis sites. Copyright © 2011 British Association of Plastic, Reconstructive and Aesthetic Surgeons. Published by Elsevier Ltd. All rights reserved.

  4. Study of complex thermosensitive amphiphilic polyoxazolines and their interaction with ionic surfactants. Are hydrophobic, thermosensitive, and hydrophilic moieties equally important?

    Czech Academy of Sciences Publication Activity Database

    Bogomolova, Anna; Filippov, Sergey K.; Starovoytova, Larisa; Angelov, Borislav; Konarev, P.; Sedláček, Ondřej; Hrubý, Martin; Štěpánek, Petr

    2014-01-01

    Roč. 118, č. 18 (2014), s. 4940-4950 ISSN 1520-6106 R&D Projects: GA ČR GAP205/11/1657; GA MPO FR-TI4/625 Grant - others:AV ČR(CZ) M200501201 Program:M Institutional support: RVO:61389013 Keywords : poly(2-alkyl-2-oxazoline) * thermosensitivity * ionic surfactant Subject RIV: CD - Macromolecular Chemistry Impact factor: 3.302, year: 2014

  5. Preparation of thermo-sensitive slow releasing material and its application in low tar tobacco

    Directory of Open Access Journals (Sweden)

    Tian Zhong

    2017-04-01

    Full Text Available To solve some sensory defects such as fragrance deficiency,strong dry sense,poor satisfaction in the development of ultra-low tar tobacco products,we prepared a new thermo sensitive slow releasing composite material with tobacco aroma.The characterization results showed that the as-prepared thermosensitive particles have better aroma enhancing and slow releasing effects.Also,the aroma components of the tip stick containing thermosensitive particles were detected and its sensory quality was evaluated.The results showed that composite tip stick could enhance the aroma and improve the sensory quality of the cigarettes.

  6. Structural and biological properties of thermosensitive chitosan-graphene hybrid hydrogels for sustained drug delivery applications.

    Science.gov (United States)

    Saeednia, Leyla; Yao, Li; Berndt, Marcus; Cluff, Kim; Asmatulu, Ramazan

    2017-09-01

    Chitosan has the ability to make injectable thermosensitive hydrogels which has been highly investigated for drug delivery applications. The addition of nanoparticles is one way to increase the mechanical strength of thermosensitive chitosan hydrogel and subsequently and control the burst release of drug. Graphene nanoparticles have shown unique mechanical, optical and electrical properties which can be exploited for biomedical applications, especially in drug delivery. This study, have focused on the mechanical properties of a thermosensitive and injectable hybrid chitosan hydrogel incorporated with graphene nanoparticles. Scanning electron microscope (SEM), Fourier transform infrared (FTIR) spectroscopy, Raman spectroscopy, and X-ray diffraction (XRD) have been used for morphological and chemical characterization of graphene infused chitosan hydrogels. The cell viability and cytotoxicity of graphene-contained hydrogels were analyzed using the alamarBlue ® technique. In-vitro methotrexate (MTX) release was investigated from MTX-loaded hybrid hydrogels as well. As a last step, to evaluate their efficiency as a cancer treatment delivery system, an in vitro anti-tumor test was also carried out using MCF-7 breast cancer cell lines. Results confirmed that a thermosensitive chitosan-graphene hybrid hydrogel can be used as a potential breast cancer therapy system for controlled delivery of methotrexate. © 2017 Wiley Periodicals, Inc. J Biomed Mater Res Part A: 105A: 2381-2390, 2017. © 2017 Wiley Periodicals, Inc.

  7. Fabrication and evaluation of thermosensitive chitosan/collagen/α, β-glycerophosphate hydrogels for tissue regeneration.

    Science.gov (United States)

    Dang, Qifeng; Liu, Kai; Zhang, Zhenzhen; Liu, Chengsheng; Liu, Xi; Xin, Ying; Cheng, Xiaoyu; Xu, Tao; Cha, Dongsu; Fan, Bing

    2017-07-01

    Thermosensitive hydrogels whose physiological properties are similar to extracellular matrix have been extensively used for tissue regeneration. Polysaccharides and proteins, as biocompatible substrates similar to bio-macromolecules that could be recognized by human body, are two preferred polymers for fabrication of such hydrogels. A series of novel thermosensitive hydrogels (CS-ASC-HGs) containing chitosan (CS) and acid-soluble collagen (ASC) were thus prepared, in the presence of α, β-glycerophosphate, to mimic extracellular microenvironment for tissue regeneration. Rheological measurements demonstrated excellent thermosensitivity. FT-IR and SEM indicated CS-ASC-HGs possessed 3D porous architectures with fibrous ASC, and the molecular structure of ASC was well-maintained in hydrogels. Hemolysis, acute toxicity, and cytotoxicity tests suggested CS-ASC-HGs were of good biocompatibility. CS-ASC-HGs were able to support the survival and proliferation of L929 cells encapsulated in them. Moreover, CS-ASC-HGs had better pH stability and biocompatibility than pure CS hydrogel. These results suggested that CS-ASC-HGs could serve as promising scaffolds for tissue regeneration. Copyright © 2017 Elsevier Ltd. All rights reserved.

  8. Dynamic culture of a thermosensitive collagen hydrogel as an extracellular matrix improves the construction of tissue-engineered peripheral nerve.

    Science.gov (United States)

    Huang, Lanfeng; Li, Rui; Liu, Wanguo; Dai, Jin; Du, Zhenwu; Wang, Xiaonan; Ma, Jianchao; Zhao, Jinsong

    2014-07-15

    Tissue engineering technologies offer new treatment strategies for the repair of peripheral nerve injury, but cell loss between seeding and adhesion to the scaffold remains inevitable. A thermosensitive collagen hydrogel was used as an extracellular matrix in this study and combined with bone marrow mesenchymal stem cells to construct tissue-engineered peripheral nerve composites in vitro. Dynamic culture was performed at an oscillating frequency of 0.5 Hz and 35° swing angle above and below the horizontal plane. The results demonstrated that bone marrow mesenchymal stem cells formed membrane-like structures around the poly-L-lactic acid scaffolds and exhibited regular alignment on the composite surface. Collagen was used to fill in the pores, and seeded cells adhered onto the poly-L-lactic acid fibers. The DNA content of the bone marrow mesenchymal stem cells was higher in the composites constructed with a thermosensitive collagen hydrogel compared with that in collagen I scaffold controls. The cellular DNA content was also higher in the thermosensitive collagen hydrogel composites constructed with the thermosensitive collagen hydrogel in dynamic culture than that in static culture. These results indicate that tissue-engineered composites formed with thermosensitive collagen hydrogel in dynamic culture can maintain larger numbers of seeded cells by avoiding cell loss during the initial adhesion stage. Moreover, seeded cells were distributed throughout the material.

  9. Extraction of americium (III) by thermosensitive polymer gel copolymerized with acidic phosphorus compound

    International Nuclear Information System (INIS)

    Takeshita, Kenji; Nakano, Yoshio; Matsumura, Tatsuro

    2001-01-01

    A new gel-liquid extraction using a thermosensitive gel was proposed. The thermosensitive gel shows the conformational change of polymer network with temperature, which is known as the phase transition phenomena of gel. The extraction rate and equilibrium of Am(III) in an aqueous solution containing nitrate ion were measured batchwise by using a thermosensitive gel, N-isopropylacrylamide (NIPA) copolymerized with 2-methacryloyloxy- ethylacidphosphate (MR). The effects of the conformational change of polymer network on the extraction rate and equilibrium were discussed. The distribution ratio of Am(III) showed a large value at higher than LCST (low critical solution temperature; 34degC) and was decreased by the phase transition of gel from shrinking to swelling with decreasing temperature. The extraction of Am(III) in the aqueous solution and the release of Am(III) extracted in the gel were repeated stably by the temperature swing operation between 40 and 3degC. The extraction mechanism of Am(III) was described simply as Am 3+ + 3R - OH=(R-O) 3 Am + 3H + (R-OH: MR). The equilibrium constant at the shrinking state (40degC) was more than 3 times of that at swelling state (3degC). The gel-phase diffusivity of Eu(III) used as a substitute of Am(III) was evaluated as the order of 10 -12 m 2 /s at either of 3 or 40degC, which was similar to those for practical extraction chromatographic resins. The temperature-response of gel for the extraction of Eu(III) was very excellent without delay even for the rapid temperature change at 10degC/min. These results suggest that the extraction and release of Am(III) in an aqueous solution can be controlled by the conformational change of polymer network of thermosensitive gel. (author)

  10. Design and synthesis study of the thermo-sensitive poly (N-vinylpyrrolidone-b- N, N-diethylacrylamide).

    Science.gov (United States)

    Zhang, Xiayun; Yang, Zhongduo; Xie, Dengmin; Liu, Donglei; Chen, Zhenbin; Li, Ke; Li, Zhizhong; Tichnell, Brandon; Liu, Zhen

    2018-01-01

    The reversible addition fragmentation chain transfer (RAFT) polymerization method was adopted here to prepare a series of thermo-sensitive copolymers, poly (N,N-diethyl- acrylamide-b-N-vinylpyrrolidone). Their structures, molecular weight distribution and temperature sensitivity performances were characterized by the nuclear magnetic resonance ( 1 HNMR), the gel permeation chromatography (GPC) and the fluorescence spectrophotometer, respectively. It has been identified that the synthesis reaction of the block copolymer was living polymerization. The thermo-sensitivity study suggested that N-vinylpyrrolidone (NVP), played a key role on the lower critical solution temperature (LCST) performance.

  11. Radiation induced variations in photoperiod-sensitivity, thermo-sensitivity and the number of days to heading in rice

    International Nuclear Information System (INIS)

    Hsieh, S.C.

    1975-01-01

    Radiation induced semi-dwarf mutants derived from five japonica type varieties of rice were studied with regard to their photoperiod-sensitivity, thermo-sensitivity and the number of days to heading. The experiment was carried out under the natural conditions at Taipei. The coefficient of photoperiod-sensitivity and thermo-sensitivity as developed by Oka (1954) were estimated for the mutants in comparison with their original varieties. It was observed that these various physiological characters could be altered easily by mutations. Mutants showed wider ranges in both positive and negative directions than their original varieties in all physiological characters studied. Even though heading date depends on both photoperiod-sensitivity and thermo-sensitivity, it was estimated which of the two contributed more to the induced earliness in each mutant. This offers a basis for selecting early maturing lines of rice

  12. Synthesis and Thermosensitive Behavior of Polyacrylamide Copolymers and Their Applications in Smart Textiles

    Directory of Open Access Journals (Sweden)

    Tao Chen

    2015-05-01

    Full Text Available We tuned the lower critical solution temperature (LCST of amphiphilic poly(N-isopropylacrylamide (PNIPAAm via copolymerization with a hydrophilic comonomer of N-hydroxymethyl acrylamide (NHMAAm. A series of copolymers P(NIPAAm-co-NHMAAm were synthesized by atom transfer radical polymerization (ATRP using CuBr/(N,N,N',N',N''-Pentamethyldiethylenetriamine (PMDETA as a catalyst system and 2-bromo ethyl isobutyrate (EBiB as an initiator. The copolymers were well characterized by Fourier transform infrared spectroscopy (FT-IR, 1H Nuclear magnetic resonance (NMR, and Thermogravimetric analysis (TGA. The copolymers followed a simple rule in their thermosensitive behaviors and have a linear increase in the LCST as a function of NHMAAm mol%. The thermosensitive properties of the copolymer films were investigated and demonstrated hydrophilic-hydrophobic transitions. Finally, the copolymer was grafted onto cotton fabrics using citric acid (CA as a crosslinking agent and sodium hypophosphite (SHP as a catalyst following a two dipping, two padding process. The large number of hydroxyl groups in the copolymer makes grafting convenient and firm. The grafted cotton fabrics show obvious thermosensitive behaviors. The results demonstrate that the cotton fabrics become more hydrophobic when the temperature is higher than the LCST. This study presents a valuable route towards temperature-responsive smart textiles and their potential applications.

  13. Thermosensitive gating effect and selective gas adsorption in a porous coordination nanocage

    NARCIS (Netherlands)

    Zhao, D.; Yuan, D.; Krishna, R.; van Baten, J.M.; Zhou, H.C.

    2010-01-01

    A porous coordination nanocage functionalized with 24 triisopropylsilyl groups exhibits a remarkable thermosensitive gate opening phenomenon and demonstrates a molecular sieving effect at a certain temperature range, which can be used for gas separation purposes.

  14. In situ delivery of thermosensitive gel-mediated 5-fluorouracil microemulsion for the treatment of colorectal cancer

    Science.gov (United States)

    Wang, Lu-Lu; Huang, Shuai; Guo, Hui-Hui; Han, Yan-Xing; Zheng, Wen-Sheng; Jiang, Jian-Dong

    2016-01-01

    In situ administration of 5-fluorouracil (5FU) “thermosensitive” gel effectively reduced systemic side effects in treating colon rectal cancer; however, the penetration efficacy of the formulation was considerably low due to the poor lipid solubility of 5FU. The aim of this study was to develop thermosensitive gel-mediated 5FU water-in-oil microemulsion (TG-5FU-ME) for improving the infiltration of 5FU. An in vitro release test showed that TG-5FU-ME sustained the drug’s release up to 10 hours. TG-5FU-ME exhibited good stability, and the microemulsion entrapped did not show any change in morphology and 5FU content during the 4-month storage. Transportation test in the Caco-2 cell monolayer showed that TG-5FU-ME had a permeability 6.3 times higher than that of 5FU thermosensitive gel, and the intracellular uptake of 5FU increased by 5.4-fold compared to that of 5FU thermosensitive gel. In vivo tissue distribution analysis exhibited that the TG-5FU-ME group had drug levels in rectal tissue and mesenteric lymph nodes, which were significantly higher than those of 5FU thermosensitive gel group, with very low blood levels of 5FU in both groups. Furthermore, TG-5FU-ME was not associated with detectable morphological damage to the rectal tissue. Conclusively, TG-5FU-ME might be an efficient rectal delivery system to treat colorectal cancer. PMID:27660416

  15. Glass transition and aging in dense suspensions of thermosensitive microgel particles

    NARCIS (Netherlands)

    Purnomo, E.H; van den Ende, Henricus T.M.; Vanapalli Veera, V.S.A.R.; Vanapalli, Srinivas; Mugele, Friedrich Gunther

    2008-01-01

    We report a thermosensitive microgel suspension that can be tuned reversibly between the glass state at low temperature and the liquid state at high temperature. Unlike hard spheres, we find that the glass transition for these suspensions is governed by both the volume fraction and the softness of

  16. Modulation of oral heat and cold pain by irritant chemicals.

    Science.gov (United States)

    Albin, Kelly C; Carstens, Mirela Iodi; Carstens, E

    2008-01-01

    Common food irritants elicit oral heat or cool sensations via actions at thermosensitive transient receptor potential (TRP) channels. We used a half-tongue, 2-alternative forced-choice procedure coupled with bilateral pain intensity ratings to investigate irritant effects on heat and cold pain. The method was validated in a bilateral thermal difference detection task. Capsaicin, mustard oil, and cinnamaldehyde enhanced lingual heat pain elicited by a 49 degrees C stimulus. Mustard oil and cinnamaldehyde weakly enhanced lingual cold pain (9.5 degrees C), whereas capsaicin had no effect. Menthol significantly enhanced cold pain and weakly reduced heat pain. To address if capsaicin's effect was due to summation of perceptually similar thermal and chemical sensations, one-half of the tongue was desensitized by application of capsaicin. Upon reapplication, capsaicin elicited little or no irritant sensation yet still significantly enhanced heat pain on the capsaicin-treated side, ruling out summation. In a third experiment, capsaicin significantly enhanced pain ratings to graded heat stimuli (47 degrees C to 50 degrees C) resulting in an upward shift of the stimulus-response function. Menthol may induce cold hyperalgesia via enhanced thermal gating of TRPM8 in peripheral fibers. Capsaicin, mustard oil, and cinnamaldehyde may induce heat hyperalgesia via enhanced thermal gating of TRPV1 that is coexpressed with TRPA1 in peripheral nociceptors.

  17. Phospholipase C δ4 regulates cold sensitivity in mice.

    Science.gov (United States)

    Yudin, Yevgen; Lutz, Brianna; Tao, Yuan-Xiang; Rohacs, Tibor

    2016-07-01

    The cold- and menthol-activated transient receptor potential melastatin 8 (TRPM8) channels are thought to be regulated by phospholipase C (PLC), but neither the specific PLC isoform nor the in vivo relevance of this regulation has been established. Here we identify PLCδ4 as the key PLC isoform involved in regulation of TRPM8 channels in vivo. We show that in small PLCδ4(-/-) TRPM8-positive dorsal root ganglion neurons cold, menthol and WS-12, a selective TRPM8 agonist, evoked significantly larger currents than in wild-type neurons, and action potential frequencies induced by menthol or by current injections were also higher in PLCδ4(-/-) neurons. PLCδ4(-/-) mice showed increased behavioural responses to evaporative cooling, and this effect was inhibited by a TRPM8 antagonist; behavioural responses to heat and mechanical stimuli were not altered. We provide evidence for the involvement of a specific PLC isoform in the regulation of cold sensitivity in mice by regulating TRPM8 activity. The transient receptor potential melastatin 8 (TRPM8) ion channel is a major sensor of environmental low temperatures. Ca(2+) -induced activation of phospholipase C (PLC) has been implied in the regulation of TRPM8 channels during menthol- and cold-induced desensitization in vitro. Here we identify PLCδ4 as the key PLC isoform involved in regulation of TRPM8 in sensory dorsal root ganglion (DRG) neurons. We identified two TRPM8-positive neuronal subpopulations, based on their cell body size. Most TRPM8-positive small neurons also responded to capsaicin, and had significantly larger menthol-induced inward current densities than medium-large cells, most of which did not respond to capsaicin. Small, but not medium-large, PLCδ4(-/-) neurons showed significantly larger currents induced by cold, menthol or WS-12, a specific TRPM8 agonist, compared to wild-type (WT) neurons, but TRPM8 protein levels were not different between the two groups. In current-clamp experiments small neurons

  18. Heat shock protein 90 (Hsp90) chaperone complex. A molecular target for enhancement of thermosensitivity and radiosensitivity

    International Nuclear Information System (INIS)

    Akimoto, Tetsuo; Nonaka, Tetsuo; Kitamoto, Yoshizumi; Sakurai, Hideyuki

    2002-01-01

    Heat shock protein 90 (Hsp90) is a highly conserved heat shock protein in animal and plants, and exists abundantly in the cytoplasm in unstressed condition, accounting for 1-2% in cytoplasmic proteins. Main difference of Hsp90 from other Hsps are its substrate that Hsp90 binds to. These substrates include various signal transduction proteins, kinase, steroid receptors and transcription factors, therefore, Hsp90 plays a key role in maintaining cellular signal transduction networks. Many chaperoned proteins (client proteins) of Hsp90 are associated with cellular proliferation or malignant transformation, thus Hsp90 chaperone complex has been focused as targets for cancer therapy. Among the client proteins, there are several molecules that have been defined as targets or factors for determination or enhancement of radiosensitivity or thermosensitivity. Thus, it is easily speculated that Hsp90 chaperone complex inhibitors that disrupt association of Hsp90 and client protein in combination with radiation or/and heat has potential effect on enhancement of radiosensitivity or thermosensitivity. In this paper, possible mechanisms in enhancing radiosensitivity or thermosensitivity according to the client proteins will be summarized. (author)

  19. N-isopropylacrylamide-based fine-dispersed thermosensitive ferrogels obtained via in-situ technique.

    Science.gov (United States)

    Korotych, O; Samchenko, Yu; Boldeskul, I; Ulberg, Z; Zholobak, N; Sukhodub, L

    2013-03-01

    Thermosensitive hydrogels with magnetic properties (ferrogels) are very promising for medical application, first of all, for the design of targeted delivery systems with controlled release of drugs and for magnetic hyperthermia and chemotherapy treatment of cancer. These magnetic hydrogels could be obtained using diverse techniques: ex- and in-situ syntheses. The present work is devoted to the study of magnetite (Fe(3)O(4)) formation inside the nanoreactors of (co)polymeric hydrogels. Polymeric templates (hydrogel films and fine-dispersed hydrogels) used for obtaining ferrogels were based on acrylic monomers: thermosensitive N-isopropylacrylamide, and hydrophilic acrylamide. Covalent cross-linking was accomplished using bifunctional monomer N,N'-methylenebisacrylamide. Influence of hydrophilic-lipophilic balance of polymeric templates and concentration of iron cations on the magnetite formation were investigated along with the development of ferrogel preparation technique. Cytotoxicity, physical and chemical properties of obtained magnetic hydrogels have been studied in this work. Copyright © 2012 Elsevier B.V. All rights reserved.

  20. MRI monitoring of nanocarrier accumulation and release using Gadolinium-SPIO co-labelled thermosensitive liposomes

    NARCIS (Netherlands)

    Lorenzato, Cyril; Oerlemans, Chris; van Elk, Merel; Geerts, Willie J C; Denis de Senneville, Baudouin; Moonen, Chrit; Bos, Clemens

    2016-01-01

    Encapsulation of anticancer drugs in triggerable nanocarriers can beneficially modify pharmacokinetics and biodistribution of chemotherapeutic drugs, and consequently increase tumor drug concentration and efficacy, while reducing side effects. Thermosensitive liposomes release their contents

  1. Formulation optimization and in vivo proof-of-concept study of thermosensitive liposomes balanced by phospholipid, elastin-like polypeptide, and cholesterol.

    Directory of Open Access Journals (Sweden)

    Sun Min Park

    Full Text Available One application of nanotechnology in medicine that is presently being developed involves a drug delivery system (DDS employing nanoparticles to deliver drugs to diseased sites in the body avoiding damage of healthy tissue. Recently, the mild hyperthermia-triggered drug delivery combined with anticancer agent-loaded thermosensitive liposomes was widely investigated. In this study, thermosensitive liposomes (TSLs, composed of 1,2-dipalmitoyl-sn-glycero-3-phosphocholine (DPPC, 1,2-distearoyl-sn-glycero-3-phosphoethanolamine-N-[methoxy(polyethyleneglycol-2000] (DSPE-PEG, cholesterol, and a fatty acid conjugated elastin-like polypeptide (ELP, were developed and optimized for triggered drug release, controlled by external heat stimuli. We introduced modified ELP, tunable for various biomedical purposes, to our thermosensitive liposome (e-TSL to convey a high thermoresponsive property. We modulated thermosensitivity and stability by varying the ratios of e-TSL components, such as phospholipid, ELP, and cholesterol. Experimental data obtained in this study corresponded to results from a simulation study that demonstrated, through the calculation of the lateral diffusion coefficient, increased permeation of the lipid bilayer with higher ELP concentrations, and decreased permeation in the presence of cholesterol. Finally, we identified effective drug accumulation in tumor tissues and antitumor efficacy with our optimized e-TSL, while adjusting lag-times for systemic accumulation.

  2. Novel cell separation method for molecular analysis of neuron-astrocyte cocultures

    Directory of Open Access Journals (Sweden)

    Andrea eGoudriaan

    2014-01-01

    Full Text Available Over the last decade, the importance of astrocyte-neuron communication in neuronal development and synaptic plasticity has become increasingly clear. Since neuron-astrocyte interactions represent highly dynamic and reciprocal processes, we hypothesized that many astrocyte genes may be regulated as a consequence of their interactions with maturing neurons. In order to identify such neuron-responsive astrocyte genes in vitro, we sought to establish an expedite technique for separation of neurons from co-cultured astrocytes. Our newly established method makes use of cold jet, which exploits different adhesion characteristics of subpopulations of cells (Jirsova et al., 1997, and is rapid, performed under ice-cold conditions and avoids protease-mediated isolation of astrocytes or time-consuming centrifugation, yielding intact astrocyte mRNA with approximately 90% of neuronal RNA removed. Using this purification method, we executed genome-wide profiling in which RNA derived from astrocyte-only cultures was compared with astrocyte RNA derived from differentiating neuron-astrocyte co-cultures. Data analysis determined that many astrocytic mRNAs and biological processes are regulated by neuronal interaction. Our results validate the cold jet as an efficient method to separate astrocytes from neurons in co-culture, and reveals that neurons induce robust gene-expression changes in co-cultured astrocytes.

  3. Using constellation pharmacology to define comprehensively a somatosensory neuronal subclass

    Science.gov (United States)

    Teichert, Russell W.; Memon, Tosifa; Aman, Joseph W.; Olivera, Baldomero M.

    2014-01-01

    Change is intrinsic to nervous systems; change is required for learning and conditioning and occurs with disease progression, normal development, and aging. To better understand mammalian nervous systems and effectively treat nervous-system disorders, it is essential to track changes in relevant individual neurons. A critical challenge is to identify and characterize the specific cell types involved and the molecular-level changes that occur in each. Using an experimental strategy called constellation pharmacology, we demonstrate that we can define a specific somatosensory neuronal subclass, cold thermosensors, across different species and track changes in these neurons as a function of development. Cold thermosensors are uniformly responsive to menthol and innocuous cool temperature (17 °C), indicating that they express TRPM8 channels. A subset of cold thermosensors expressed α7 nicotinic acetylcholine receptors (nAChRs) but not other nAChR subtypes. Differences in temperature threshold of cold thermosensors correlated with functional expression of voltage-gated K channels Kv1.1/1.2: Relatively higher expression of KV1.1/1.2 channels resulted in a higher threshold response to cold temperature. Other signaling components varied during development and between species. In cold thermosensors of neonatal mice and rats, ATP receptors were functionally expressed, but the expression disappeared with development. This developmental change occurred earlier in low-threshold than high-threshold cold thermosensors. Most rat cold thermosensors expressed TRPA1 channels, whereas mouse cold thermosensors did not. The broad implications of this study are that it is now feasible to track changes in receptor and ion-channel expression in individual neuronal subclasses as a function of development, learning, disease, or aging. PMID:24469798

  4. Thermosensitive copolymeric hydrogels with the regulated temperature of a phase transition

    International Nuclear Information System (INIS)

    Samchenko, Yu.M.; Konovalova, V.V.; Korotich, E.I.; Poltoratskaya, T.P.; Pobegaj, A.A.; Burban, A.F.; Ul'berg, Z.R.; Samchenko, Yu.M.; Konovalova, V.V.; Korotich, E.I.; Poltoratskaya, T.P.; Pobegaj, A.A.; Burban, A.F.; Ul'berg, Z.R.

    2011-01-01

    The work is devoted to the methods of obtaining the thermosensitive copolymeric hydrogels based on the NIPAAm with acrylic acid and its derivatives such as acrylamide, acrylonitrile, and methylacrylate. The mechanisms of thermoinitiated phase transitions in hydrogel matrices and the regularities of the thermoinitiated release of model compounds and drugs (aniline, novocaine, and sodium diclofenac) from copolymeric hydrogel are investigated.

  5. Thermo-sensitive injectable glycol chitosan-based hydrogel for treatment of degenerative disc disease.

    Science.gov (United States)

    Li, Zhengzheng; Shim, Hyeeun; Cho, Myeong Ok; Cho, Ik Sung; Lee, Jin Hyun; Kang, Sun-Woong; Kwon, Bosun; Huh, Kang Moo

    2018-03-15

    The use of injectable hydrogel formulations have been suggested as a promising strategy for the treatment of degenerative disc disease to both restore the biomechanical function and reduce low back pain. In this work, a new thermo-sensitive injectable hydrogels with tunable thermo-sensitivity and enhanced stability were developed with N-hexanoylation of glycol chitosan (GC) for treatment of degenerative disc disease, and their physico-chemical and biological properties were evaluated. The sol-gel transition temperature of the hydrogels was controlled in a range of 23-56 °С, depending on the degree of hexanoylation and the polymer concentration. In vitro and in vivo tests showed no cytotoxicity and no adverse effects in a rat model. The hydrogel filling of the defective IVD site in an ex vivo porcine model maintained its stability for longer than 28 days. These results suggest that the hydrogel can be used as an alternative material for treatment of disc herniation. Copyright © 2018 Elsevier Ltd. All rights reserved.

  6. Ion channel profile of TRPM8 cold receptors reveals a novel role of TASK-3 potassium channels in thermosensation

    Science.gov (United States)

    Morenilla-Palao, Cruz; Luis, Enoch; Fernández-Peña, Carlos; Quintero, Eva; Weaver, Janelle L.; Bayliss, Douglas A.; Viana, Félix

    2017-01-01

    Summary Animals sense cold ambient temperatures through the activation of peripheral thermoreceptors that express TRPM8, a cold- and menthol-activated ion channel. These receptors can discriminate a very wide range of temperatures from innocuous to noxious. The molecular mechanism responsible for the variable sensitivity of individual cold receptors to temperature is unclear. To address this question, we performed a detailed ion channel expression analysis of cold sensitive neurons, combining BAC transgenesis with a molecular profiling approach in FACS purified TRPM8 neurons. We found that TASK-3 leak potassium channels are highly enriched in a subpopulation of these sensory neurons. The thermal threshold of TRPM8 cold neurons is decreased during TASK-3 blockade and in mice lacking TASK-3 and, most importantly, these mice display hypersensitivity to cold. Our results demonstrate a novel role of TASK-3 channels in thermosensation, showing that a channel-based combinatorial strategy in TRPM8 cold thermoreceptors leads to molecular specialization and functional diversity. PMID:25199828

  7. Electrostatic Self-Assembly of Au Nanoparticles onto Thermosensitive Magnetic Core-Shell Microgels for Thermally Tunable and Magnetically Recyclable Catalysis.

    Science.gov (United States)

    Liu, Guoqiang; Wang, Daoai; Zhou, Feng; Liu, Weimin

    2015-06-01

    A facile route to fabricate a nanocomposite of Fe3O4@poly[N-isopropylacrylamide (NIPAM)-co-2-(dimethylamino)ethyl methacrylate (DMAEMA)]@Au (Fe3O4@PND@Au) is developed for magnetically recyclable and thermally tunable catalysis. The negatively charged Au nanoparticles with an average diameter of 10 nm are homogeneously loaded onto positively charged thermoresponsive magnetic core-shell microgels of Fe3O4@poly(NIPAM-co-DMAEMA) (Fe3O4@PND) through electrostatic self-assembly. This type of attachment offers perspectives for using charged polymeric shell on a broad variety of nanoparticles to immobilize the opposite-charged nanoparticles. The thermosensitive PND shell with swollen or collapsed properties can be as a retractable Au carrier, thereby tuning the aggregation or dispersion of Au nanoparticles, which leads to an increase or decrease of catalytic activity. Therefore, the catalytic activity of Fe3O4@PND@Au can be modulated by the volume transition of thermosensitive microgel shells. Importantly, the mode of tuning the aggregation or dispersion of Au nanoparticles using a thermosensitive carrier offers a novel strategy to adjust and control the catalytic activity, which is completely different with the traditional regulation mode of controlling the diffusion of reactants toward the catalytic Au core using the thermosensitive poly(N-isopropylacrylamide) network as a nanogate. Concurrent with the thermally tunable catalysis, the magnetic susceptibility of magnetic cores enables the Fe3O4@PND@Au nanocomposites to be capable of serving as smart nanoreactors for thermally tunable and magnetically recyclable catalysis. © 2015 WILEY-VCH Verlag GmbH & Co. KGaA, Weinheim.

  8. Membrane distillation with porous metal hollow fibers for the concentration of thermo-sensitive solutions

    NARCIS (Netherlands)

    Shukla, Sushumna

    2014-01-01

    This thesis presents an original approach for the concentration of thermo-sensitive solutions: the Sweep Gas Membrane Distillation (SGMD) process. A new membrane contactor with metallic hollow fibers has been designed and allows the distillation process to be operational at low temperature. Heat is

  9. Sustained Morphine Administration Induces TRPM8-Dependent Cold Hyperalgesia.

    Science.gov (United States)

    Gong, Kerui; Jasmin, Luc

    2017-02-01

    It is not uncommon for patients chronically treated with opioids to exhibit opioid-induced hyperalgesia, and this has been widely reported clinically and experimentally. The molecular substrate for this hyperalgesia is multifaceted, and associated with a complex neural reorganization even in the periphery. For instance, we have recently shown that chronic morphine-induced heat hyperalgesia is associated with an increased expression of GluN2B containing N-methyl-D-aspartate receptors, as well as of the neuronal excitatory amino acid transporter 3/excitatory amino acid carrier 1, in small-diameter primary sensory neurons only. Cold allodynia is also a common complaint of patients chronically treated with opioids, yet its molecular mechanisms remain to be understood. Here we present evidence that the cold sensor TRPM8 channel is involved in opioid-induced hyperalgesia. After 7 days of morphine administration, we observed an upregulation of TRPM8 channels using patch clamp recording on sensory neurons and Western blot analysis on dorsal root ganglia. The selective TRPM8 antagonist RQ-00203078 blocked cold hyperalgesia in morphine-treated rats. Also, TRPM8 knockout mice failed to develop cold hyperalgesia after chronic administration of morphine. Our results show that chronic morphine upregulates TRPM8 channels, which is in contrast with the previous finding that acute morphine triggers TRPM8 internalization. Patients receiving chronic opioid are sensitive to cold. We show in mice and rats that sustained morphine administration induces cold hyperalgesia and an upregulation of TRPM8. Knockout or selectively blocking TRPM8 reduces morphine-induced cold hyperalgesia suggesting TRPM8 is regulated by opioids. Copyright © 2016 American Pain Society. Published by Elsevier Inc. All rights reserved.

  10. Enhanced gelation of chitosan/β-sodium glycerophosphate thermosensitive hydrogel with sodium bicarbonate and biocompatibility evaluated.

    Science.gov (United States)

    Deng, Aipeng; Kang, Xi; Zhang, Jing; Yang, Yang; Yang, Shulin

    2017-09-01

    The application of chitosan/β-sodium glycerophosphate (β-GP) thermosensitive hydrogel has been limited by the relatively slow gelation, weak mechanical resistance and poor cytocompatibility. In this study, sodium hydrogen carbonate (NaHCO 3 ) was applied with β-GP as gel agents to produce high-strength hydrogel. The hydrogels prepared with high NaHCO 3 concentration or more gel agents showed shorter gelation time, better thermostability, drastically enhanced resistance in compression. Meanwhile, the hydrogels presented obvious porous structures and excellent biocompatibility to HUVEC and NIH 3T3 cultured in vitro with higher NaHCO 3 concentration and moderate concentration of β-GP. Overall, appropriate concentration of β-GP combined with NaHCO 3 can be a good gel regent to improve properties of chitosan thermosensitive hydrogels. Copyright © 2017 Elsevier B.V. All rights reserved.

  11. Novel thermo-sensitive core-shell nanoparticles for targeted paclitaxel delivery

    International Nuclear Information System (INIS)

    Li Yuanpei; Pan Shirong; Zhang Wei; Du Zhuo

    2009-01-01

    Novel thermo-sensitive nanoparticles self-assembled from poly(N,N-diethylacrylamide- co-acrylamide)-block-poly(γ-benzyl L-glutamate) were designed for targeted drug delivery in localized hyperthermia. The lower critical solution temperature (LCST) of nanoparticles was adjusted to a level between physiological body temperature (37 deg. C) and that used in local hyperthermia (about 43 deg. C). The temperature-dependent performances of the core-shell nanoparticles were systemically studied by nuclear magnetic resonance (NMR), circular dichroism (CD), fluorescence spectroscopy, dynamic light scattering (DLS), and atom force microscopy (AFM). The mean diameter of the nanoparticles increased slightly from 110 to 129 nm when paclitaxel (PTX), a poorly water-soluble anti-tumor drug, was encapsulated. A stability study in bovine serum albumin (BSA) solution indicated that the PTX loaded nanoparticles may have a long circulation time under physiological environments as the LCST was above physiological body temperature and the shell remained hydrophilic at 37 deg.C. The PTX release profiles showed thermo-sensitive controlled behavior. The proliferation inhibiting activity of PTX loaded nanoparticles was evaluated against Hela cells in vitro, compared with Taxol (a formulation of paclitaxel dissolved in Cremophor EL and ethanol). The cytotoxicity of PTX loaded nanoparticles increased obviously when hyperthermia was performed. The nanoparticles synthesized here could be an ideal candidate for thermal triggered anti-tumor PTX delivery system.

  12. Delay-induced diversity of firing behavior and ordered chaotic firing in adaptive neuronal networks

    International Nuclear Information System (INIS)

    Gong Yubing; Wang Li; Xu Bo

    2012-01-01

    In this paper, we study the effect of time delay on the firing behavior and temporal coherence and synchronization in Newman–Watts thermosensitive neuron networks with adaptive coupling. At beginning, the firing exhibit disordered spiking in absence of time delay. As time delay is increased, the neurons exhibit diversity of firing behaviors including bursting with multiple spikes in a burst, spiking, bursting with four, three and two spikes, firing death, and bursting with increasing amplitude. The spiking is the most ordered, exhibiting coherence resonance (CR)-like behavior, and the firing synchronization becomes enhanced with the increase of time delay. As growth rate of coupling strength or network randomness increases, CR-like behavior shifts to smaller time delay and the synchronization of firing increases. These results show that time delay can induce diversity of firing behaviors in adaptive neuronal networks, and can order the chaotic firing by enhancing and optimizing the temporal coherence and enhancing the synchronization of firing. However, the phenomenon of firing death shows that time delay may inhibit the firing of adaptive neuronal networks. These findings provide new insight into the role of time delay in the firing activity of adaptive neuronal networks, and can help to better understand the complex firing phenomena in neural networks.

  13. Delimitation of the embryonic thermosensitive period for sex determination using an embryo growth model reveals a potential bias for sex ratio prediction in turtles.

    Science.gov (United States)

    Girondot, Marc; Monsinjon, Jonathan; Guillon, Jean-Michel

    2018-04-01

    The sexual phenotype of the gonad is dependent on incubation temperature in many turtles, all crocodilians, and some lepidosaurians. At hatching, identification of sexual phenotype is impossible without sacrificing the neonates. For this reason, a general method to infer sexual phenotype from incubation temperatures is needed. Temperature influences sex determination during a specific period of the embryonic development, starting when the gonad begins to form. At constant incubation temperatures, this thermosensitive period for sex determination (TSP) is located at the middle third of incubation duration (MTID). When temperature fluctuates, the position of the thermosensitive period for sex determination can be shifted from the MTID because embryo growth is affected by temperature. A method is proposed to locate the thermosensitive period for sex determination based on modelling the embryo growth, allowing its precise identification from a natural regime of temperatures. Results from natural nests and simulations show that the approximation of the thermosensitive period for sex determination to the middle third of incubation duration may create a quasi-systematic bias to lower temperatures when computing the average incubation temperature during this period and thus a male-bias for sex ratio estimate. Copyright © 2018 Elsevier Ltd. All rights reserved.

  14. The contribution of TRPM8 and TRPA1 channels to cold allodynia and neuropathic pain.

    Science.gov (United States)

    Caspani, Ombretta; Zurborg, Sandra; Labuz, Dominika; Heppenstall, Paul A

    2009-10-08

    Cold allodynia is a common feature of neuropathic pain however the underlying mechanisms of this enhanced sensitivity to cold are not known. Recently the transient receptor potential (TRP) channels TRPM8 and TRPA1 have been identified and proposed to be molecular sensors for cold. Here we have investigated the expression of TRPM8 and TRPA1 mRNA in the dorsal root ganglia (DRG) and examined the cold sensitivity of peripheral sensory neurons in the chronic construction injury (CCI) model of neuropathic pain in mice.In behavioral experiments, chronic constriction injury (CCI) of the sciatic nerve induced a hypersensitivity to both cold and the TRPM8 agonist menthol that developed 2 days post injury and remained stable for at least 2 weeks. Using quantitative RT-PCR and in situ hybridization we examined the expression of TRPM8 and TRPA1 in DRG. Both channels displayed significantly reduced expression levels after injury with no change in their distribution pattern in identified neuronal subpopulations. Furthermore, in calcium imaging experiments, we detected no alterations in the number of cold or menthol responsive neurons in the DRG, or in the functional properties of cold transduction following injury. Intriguingly however, responses to the TRPA1 agonist mustard oil were strongly reduced.Our results indicate that injured sensory neurons do not develop abnormal cold sensitivity after chronic constriction injury and that alterations in the expression of TRPM8 and TRPA1 are unlikely to contribute directly to the pathogenesis of cold allodynia in this neuropathic pain model.

  15. The contribution of TRPM8 and TRPA1 channels to cold allodynia and neuropathic pain.

    Directory of Open Access Journals (Sweden)

    Ombretta Caspani

    Full Text Available Cold allodynia is a common feature of neuropathic pain however the underlying mechanisms of this enhanced sensitivity to cold are not known. Recently the transient receptor potential (TRP channels TRPM8 and TRPA1 have been identified and proposed to be molecular sensors for cold. Here we have investigated the expression of TRPM8 and TRPA1 mRNA in the dorsal root ganglia (DRG and examined the cold sensitivity of peripheral sensory neurons in the chronic construction injury (CCI model of neuropathic pain in mice.In behavioral experiments, chronic constriction injury (CCI of the sciatic nerve induced a hypersensitivity to both cold and the TRPM8 agonist menthol that developed 2 days post injury and remained stable for at least 2 weeks. Using quantitative RT-PCR and in situ hybridization we examined the expression of TRPM8 and TRPA1 in DRG. Both channels displayed significantly reduced expression levels after injury with no change in their distribution pattern in identified neuronal subpopulations. Furthermore, in calcium imaging experiments, we detected no alterations in the number of cold or menthol responsive neurons in the DRG, or in the functional properties of cold transduction following injury. Intriguingly however, responses to the TRPA1 agonist mustard oil were strongly reduced.Our results indicate that injured sensory neurons do not develop abnormal cold sensitivity after chronic constriction injury and that alterations in the expression of TRPM8 and TRPA1 are unlikely to contribute directly to the pathogenesis of cold allodynia in this neuropathic pain model.

  16. A study on the thermochemotherapy effect of nanosized As2O3/MZF thermosensitive magnetoliposomes on experimental hepatoma in vitro and in vivo

    Science.gov (United States)

    Wang, Li; Zhang, Jia; An, Yanli; Wang, Ziyu; Liu, Jing; Li, Yutao; Zhang, Dongsheng

    2011-08-01

    In this paper, we describe the synthesis and characterization of a nanosized, thermosensitive magnetoliposome encapsulating magnetic nanoparticles (MZFs) and antitumor drugs (As2O3). The nanoliposomes were spherical and mostly single volume, with an average diameter of 128.2 nm. Differential scanning calorimetry (DSC) showed a liposome phase transition temperature of 42.71 °C. After that, we studied the liposomes' anti-hepatoma effect in vitro and in vivo. The antitumor effect of the nanoliposomes on human hepatoma cells, SMMC-7721, and changes in expression of apoptosis-related proteins were examined in vitro. The results show that As2O3/MZF thermosensitive magnetoliposomes combined with hyperthermia had a great impact on the Bax/Bcl-2 ratio, which increased to 1.914 and exhibited a rapid response to induce apoptosis of tumor cells. An in situ rabbit liver tumor model was established and used to evaluate the antitumor effect of combined hyperthermia and chemotherapy following transcatheter arterial embolization with As2O3/MZF thermosensitive magnetoliposomes. The results demonstrated a strong anti-hepatoma effect, with a tumor volume inhibition rate of up to 85.22%. Thus, As2O3/MZF thermosensitive magnetoliposomes may play a great role in the treatment of hepatocarcinoma.

  17. Hairy polyelectrolyte brushes-grafted thermosensitive microgels as artificial synovial fluid for simultaneous biomimetic lubrication and arthritis treatment.

    Science.gov (United States)

    Liu, Guoqiang; Liu, Zhilu; Li, Na; Wang, Xiaolong; Zhou, Feng; Liu, Weimin

    2014-11-26

    We report the fabrication of poly(3-sulfopropyl methacrylate potassium salt) (PSPMK) brushes grafted poly(N-isopropylacrylamide) (PNIPAAm) microgels and their potential as artificial synovial fluid for biomimetic aqueous lubrication and arthritis treatment. The negatively charged PSPMK brushes and thermosensitive PNIPAAm microgels play water-based hydration lubrication and temperature-triggered drug release, respectively. Under soft friction pairs, an ultralow coefficient of friction was achieved, while the hairy thermosensitive microgels showed a desirable temperature-triggered drugs release performance. Such a soft charged hairy microgel offers great possibility for designing intelligent synovial fluid. What is more, the combination of lubrication and drug loading capabilities enables the large clinical potential of novel soft hairy nanoparticles as synthetic joint lubricant fluid in arthritis treatment.

  18. Neuropeptide Y receptor-expressing dorsal horn neurons: role in nocifensive reflex and operant responses to aversive cold after CFA inflammation.

    Science.gov (United States)

    Lemons, L L; Wiley, R G

    2012-08-02

    The spinal Neuropeptide Y (NPY) system is a potential target for development of new pain therapeutics. NPY and two of its receptors (Y1 and Y2) are found in the superficial dorsal horn of the spinal cord, a key area of nociceptive gating and modulation. Lumbar intrathecal injection of (NPY) is antinociceptive, reducing hyper-reflexia to thermal and mechanical stimulation, particularly after nerve injury and inflammation. We have also shown that intrathecal injection of the targeted cytotoxin, Neuropeptide Y-sap (NPY-sap), is also antinociceptive, reducing nocifensive reflex responses to noxious heat and formalin. In the present study, we sought to determine the role of dorsal horn Y1R-expressing neurons in pain by destroying them with NPY-sap and testing the rats on three operant tasks. Lumbar intrathecal NPY-sap (1) reduced Complete Freund's Adjuvant (CFA)-induced hyper-reflexia on the 10°C cold plate, (2) reduced cold aversion on the thermal preference and escape tasks, (3) was analgesic to noxious heat on the escape task, (4) reduced the CFA-induced allodynia to cold temperatures experienced on the thermal preference, feeding interference, and escape tasks, and (5) did not inhibit or interfere with morphine analgesia. Published by Elsevier Ltd.

  19. Thermosensitive membranes by radiation-induced graft polymerization of N-isopropyl acrylamide/acrylic acid on polypropylene nonwoven fabric

    International Nuclear Information System (INIS)

    Ikram, Saiqa; Kumari, Mamta; Gupta, Bhuvanesh

    2011-01-01

    Radiation-induced graft copolymerization of N-isopropylacrylamide (NIPAAm) and acrylic acid (AA) mixture was investigated on polypropylene nonwoven fabric to develop a thermosensitive material. The grafting was carried out using methanol, acetone and butanone as homopolymerization inhibitor in the reaction medium. Butanone was observed to give the maximum grafting. It was observed that the grafting is significantly influenced by the reaction conditions, such as radiation dose, monomer concentration, monomer ratio, solvent composition and reaction temperature. The degree of grafting increased as the AA and NIPAAm concentration in the reaction medium increased. The degree of grafting increased as the AA fraction in the NIPAAm/AA mixture increased. The temperature dependence of the grafting process is very much governed by the thermosensitive nature of the grafted chains right from the stage when initial grafting has taken place.

  20. Thermosensitive membranes by radiation-induced graft polymerization of N-isopropyl acrylamide/acrylic acid on polypropylene nonwoven fabric

    Energy Technology Data Exchange (ETDEWEB)

    Ikram, Saiqa; Kumari, Mamta [Department of Chemistry, Jamia Millia Islamia (Central University), New Delhi-110025 (India); Gupta, Bhuvanesh, E-mail: bgupta@textile.iitd.ernet.i [Department of Textile Technology, Indian Institute of Technology, New Delhi-110016 (India)

    2011-01-15

    Radiation-induced graft copolymerization of N-isopropylacrylamide (NIPAAm) and acrylic acid (AA) mixture was investigated on polypropylene nonwoven fabric to develop a thermosensitive material. The grafting was carried out using methanol, acetone and butanone as homopolymerization inhibitor in the reaction medium. Butanone was observed to give the maximum grafting. It was observed that the grafting is significantly influenced by the reaction conditions, such as radiation dose, monomer concentration, monomer ratio, solvent composition and reaction temperature. The degree of grafting increased as the AA and NIPAAm concentration in the reaction medium increased. The degree of grafting increased as the AA fraction in the NIPAAm/AA mixture increased. The temperature dependence of the grafting process is very much governed by the thermosensitive nature of the grafted chains right from the stage when initial grafting has taken place.

  1. Thermotolerance and thermosensitization in CHO and R1H cells: a comparative study

    International Nuclear Information System (INIS)

    Dikomey, E.; Eickhoff, J.; Jung, H.

    1984-01-01

    In CHO and R1H cells thermotolerance was induced by a pre-incubation at 40 0 C, by an acute heat shock at 43 0 C followed by a time interval at 37 0 C, and during continuous heating at 42 0 C. Thermotolerance, which was tested at 43 0 , primarily causes an increase in D 0 of the heat-response curve. The degree of maximum thermotolerance was found to be generally more pronounced in CHO than in R1H cells, but the time interval at 37 0 C, as well as at 40 0 C, to reach this maximum level was the same in both cell lines. CHO and R1H cells could be sensitized to 40 0 C by a pre-treatment at 43 0 C. When compared for the same survival rate after pre-treatment at 43 0 C alone the degree of thermosensitization was about the same in both cell lines. In either cell line thermosensitization was found to be suppressed when cells were made thermotolerant by a previous incubation at 40 0 C for 16 hours. (author)

  2. Enhancing Antidepressant Effect of Poloxamer/Chitosan Thermosensitive Gel Containing Curcumin-Cyclodextrin Inclusion Complex

    Directory of Open Access Journals (Sweden)

    Ye Zhang

    2018-01-01

    Full Text Available Poor solubility and bioavailability are limiting factors for the clinical application of curcumin. This study seeks to develop poloxamer/chitosan thermosensitive gel containing curcumin-cyclodextrin inclusion complex with enhanced brain bioavailability and antidepressant effect. The optimized gel had shorter gelation time and produced sustained release in vitro characterized with non-Fickian diffusion. Pharmacokinetics of gel were evaluated using male Sprague-Dawley rats receiving 240 μg/kg of curcumin and curcumin-cyclodextrin inclusion complex through intranasal administration, compared against a control group receiving intravenous curcumin (240 μg/kg. The intranasal administration of gel provided sustained release by maintaining plasma concentrations of curcumin above 21.27 ± 3.26 ng/mL for up to 8 h. Compared to intranasal administration of the inclusion complex, AUC0–8 h of curcumin from thermoreversible gel in plasma and hippocampus was increased 1.62- and 1.28-fold, respectively. The gel exhibited superior antidepressant activity in mice. The findings reported here suggested that the clinical application of curcumin can be better exploited through an intranasal administration of the thermosensitive gel.

  3. Increasing dwell time of mitomycin C in the upper tract with a reverse thermosensitive polymer.

    Science.gov (United States)

    Wang, Agnes J; Goldsmith, Zachariah G; Neisius, Andreas; Astroza, Gaston M; Oredein-McCoy, Olugbemisola; Iqbal, Muhammad W; Simmons, W Neal; Madden, John F; Preminger, Glenn M; Inman, Brant A; Lipkin, Michael E; Ferrandino, Michael N

    2013-03-01

    Abstract Background and Purpose: Topical chemotherapy for urothelial cancer is dependent on adequate contact time of the chemotherapeutic agent with the urothelium. To date, there has not been a reliable method of maintaining this contact for renal or ureteral urothelial carcinoma. We evaluated the safety and feasibility of using a reverse thermosensitive polymer to improve dwell times of mitomycin C (MMC) in the upper tract. Using a porcine model, four animals were treated ureteroscopically with both upper urinary tracts receiving MMC mixed with iodinated contrast. One additional animal received MMC percutaneously. The treatment side had ureteral outflow blocked with a reverse thermosensitive polymer plug. MMC dwell time was monitored fluoroscopically and intrarenal pressures measured. Two animals were euthanized immediately, and three animals were euthanized 5 days afterward. In control kidneys, drainage occurred at a mean of 5.3±0.58 minutes. Intrarenal pressures stayed fairly stable: 9.7±14.0 cm H20. In treatment kidneys, dwell time was extended to 60 minutes, when the polymer was washed out. Intrarenal pressures in the treatment kidneys peaked at 75.0±14.7 cm H20 and reached steady state at 60 cm H20. Pressures normalized after washout of the polymer with cool saline. Average washout time was 11.8±9.6 minutes. No histopathologic differences were seen between the control and treatment kidneys, or with immediate compared with delayed euthanasia. A reverse thermosensitive polymer can retain MMC in the upper urinary tract and appears to be safe from our examination of intrarenal pressures and histopathology. This technique may improve the efficacy of topical chemotherapy in the management of upper tract urothelial carcinoma.

  4. A study on the thermochemotherapy effect of nanosized As{sub 2}O{sub 3}/MZF thermosensitive magnetoliposomes on experimental hepatoma in vitro and in vivo

    Energy Technology Data Exchange (ETDEWEB)

    Wang Li; Zhang Jia; Wang Ziyu; Liu Jing; Li Yutao; Zhang Dongsheng [School of Medicine, Southeast University, NO. 87 Ding jia qiao, Nanjing 210009 (China); An Yanli, E-mail: wangli040418@163.com, E-mail: zdszds1222@163.com [Affiliated Zhong-Da Hospital of Southeast University, Nanjing 210009 (China)

    2011-08-05

    In this paper, we describe the synthesis and characterization of a nanosized, thermosensitive magnetoliposome encapsulating magnetic nanoparticles (MZFs) and antitumor drugs (As{sub 2}O{sub 3}). The nanoliposomes were spherical and mostly single volume, with an average diameter of 128.2 nm. Differential scanning calorimetry (DSC) showed a liposome phase transition temperature of 42.71 deg. C. After that, we studied the liposomes' anti-hepatoma effect in vitro and in vivo. The antitumor effect of the nanoliposomes on human hepatoma cells, SMMC-7721, and changes in expression of apoptosis-related proteins were examined in vitro. The results show that As{sub 2}O{sub 3}/MZF thermosensitive magnetoliposomes combined with hyperthermia had a great impact on the Bax/Bcl-2 ratio, which increased to 1.914 and exhibited a rapid response to induce apoptosis of tumor cells. An in situ rabbit liver tumor model was established and used to evaluate the antitumor effect of combined hyperthermia and chemotherapy following transcatheter arterial embolization with As{sub 2}O{sub 3}/MZF thermosensitive magnetoliposomes. The results demonstrated a strong anti-hepatoma effect, with a tumor volume inhibition rate of up to 85.22%. Thus, As{sub 2}O{sub 3}/MZF thermosensitive magnetoliposomes may play a great role in the treatment of hepatocarcinoma.

  5. Thermo-sensitive TRP channels in peripheral nerve injury: a review of their role in cold intolerance

    NARCIS (Netherlands)

    Kambiz, S.; Duraku, L.S.; Holstege, J.C.; Hovius, S.E.; Ruigrok, T.J.; Walbeehm, E.T.

    2014-01-01

    One of the sensory complications of traumatic peripheral nerve injury is thermal intolerance, which manifests in humans mainly as cold intolerance. It has a major effect on the quality of life, and adequate therapy is not yet available. In order to better understand the pathophysiological background

  6. Oxide nanomembrane hybrids with enhanced mechano- and thermo-sensitivity for semitransparent epidermal electronics.

    Science.gov (United States)

    Park, Minjoon; Do, Kyungsik; Kim, Jaemin; Son, Donghee; Koo, Ja Hoon; Park, Jinkyung; Song, Jun-Kyul; Kim, Ji Hoon; Lee, Minbaek; Hyeon, Taeghwan; Kim, Dae-Hyeong

    2015-05-01

    Oxide nanomembrane hybrids with enhanced mechano- and thermo-sensitivity for semitransparent epidermal electronics are developed. The use of nanomaterials (single wall nanotubes and silver nanoparticles) embedded in the oxide nanomembranes significantly enhances mechanical and thermal sensitivities. These mechanical and thermal sensors are utilized in wheelchair control and hypothermia detection, which are useful for patients with strokes. © 2015 WILEY-VCH Verlag GmbH & Co. KGaA, Weinheim.

  7. Glycolytic metabolite methylglyoxal inhibits cold and menthol activation of the transient receptor potential melastatin type 8 channel.

    Science.gov (United States)

    Ciobanu, A C; Selescu, T; Gasler, I; Soltuzu, L; Babes, A

    2016-03-01

    Methylglyoxal (MG) is a reactive dicarbonyl compound involved in protein modifications linked to diabetes mellitus. The plasma level of MG is elevated in diabetic patients, particularly those with painful diabetic neuropathy. Diabetic neuropathy is often associated with spontaneous pain and altered thermal perception. This study assesses effects of MG on TRPM8, an ion channel involved in innocuous cold sensing and cold allodynia and also in cold-mediated analgesia. Acute treatment with MG inhibited the activation of recombinant rat and human transient receptor potential melastatin type 8 (TRPM8) by cold and chemical agonists. A similar effect was observed when native TRPM8 was investigated in cultured rat dorsal root ganglion (DRG) neurons. DRG neurons treated with MG for 16-24 hr displayed a significant reduction in the fraction of cold- and menthol-sensitive neurons, most likely expressing TRPM8. The fraction of allyl isothiocyanate-sensitive neurons was also reduced, and the coexpression among different neuronal populations was affected. The same prolonged exposure to MG significantly reduced the expression of TRPM8 at the mRNA level. Overall, our data provide evidence for decreased activity and expression level of TRPM8 in the presence of MG, which may be linked to some of the alterations in pain and temperature sensing reported by diabetic patients. © 2015 Wiley Periodicals, Inc. © 2015 Wiley Periodicals, Inc.

  8. Smart thermosensitive liposomes for effective solid tumor therapy and in vivo imaging.

    Directory of Open Access Journals (Sweden)

    Kevin Affram

    Full Text Available In numerous studies, liposomes have been used to deliver anticancer drugs such as doxorubicin to local heat-triggered tumor. Here, we investigate: (i the ability of thermosensitive liposomal nanoparticle (TSLnp as a delivery system to deliver poorly membrane-permeable anticancer drug, gemcitabine (Gem to solid pancreatic tumor with the aid of local mild hyperthermia and, (ii the possibility of using gadolinium (Magnevist® loaded-TSLnps (Gd-TSLnps to increase magnetic resonance imaging (MRI contrast in solid tumor. In this study, we developed and tested gemcitabine-loaded thermosensitive liposomal nanoparticles (Gem-TSLnps and gadolinium-loaded thermosensitive liposomal nanoparticles (Gd-TSLnps both in in-vitro and in-vivo. The TSLnps exhibited temperature-dependent release of Gem, at 40-42°C, 65% of Gem was released within 10 min, whereas < 23% Gem leakage occurred at 37°C after a period of 2 h. The pharmacokinetic parameters and tissue distribution of both Gem-TSLnps and Gd-TSLnps were significantly greater compared with free Gem and Gd, while Gem-TSLnps plasma clearance was reduced by 17-fold and that of Gd-TSLpns was decreased by 2-fold. Area under the plasma concentration time curve (AUC of Gem-TSLnps (35.17± 0.04 μghr/mL was significantly higher than that of free Gem (2.09 ± 0.01 μghr/mL whereas, AUC of Gd-TSLnps was higher than free Gd by 3.9 fold high. TSLnps showed significant Gem accumulation in heated tumor relative to free Gem. Similar trend of increased Gd-TSLnps accumulation was observed in non-heated tumor compared to that of free Gd; however, no significant difference in MRI contrast enhancement between free Gd and Gd-TSLnps ex-vivo tumor images was observed. Despite Gem-TSLnps dose being half of free Gem dose, antitumor efficacy of Gem-TSLnps was comparable to that of free Gem(Gem-TSLnps 10 mg Gem/kg compared with free Gem 20 mg/kg. Overall, the findings suggest that TSLnps may be used to improve Gem delivery and enhance

  9. Activation of hypothalamic RIP-Cre neurons promotes beiging of WAT via sympathetic nervous system.

    Science.gov (United States)

    Wang, Baile; Li, Ang; Li, Xiaomu; Ho, Philip Wl; Wu, Donghai; Wang, Xiaoqi; Liu, Zhuohao; Wu, Kelvin Kl; Yau, Sonata Sy; Xu, Aimin; Cheng, Kenneth Ky

    2018-04-01

    Activation of brown adipose tissue (BAT) and beige fat by cold increases energy expenditure. Although their activation is known to be differentially regulated in part by hypothalamus, the underlying neural pathways and populations remain poorly characterized. Here, we show that activation of rat-insulin-promoter-Cre (RIP-Cre) neurons in ventromedial hypothalamus (VMH) preferentially promotes recruitment of beige fat via a selective control of sympathetic nervous system (SNS) outflow to subcutaneous white adipose tissue (sWAT), but has no effect on BAT Genetic ablation of APPL2 in RIP-Cre neurons diminishes beiging in sWAT without affecting BAT, leading to cold intolerance and obesity in mice. Such defects are reversed by activation of RIP-Cre neurons, inactivation of VMH AMPK, or treatment with a β3-adrenergic receptor agonist. Hypothalamic APPL2 enhances neuronal activation in VMH RIP-Cre neurons and raphe pallidus, thereby eliciting SNS outflow to sWAT and subsequent beiging. These data suggest that beige fat can be selectively activated by VMH RIP-Cre neurons, in which the APPL2-AMPK signaling axis is crucial for this defending mechanism to cold and obesity. © 2018 The Authors.

  10. Investigation of a new thermosensitive block copolymer micelle: hydrolysis, disruption, and release.

    Science.gov (United States)

    Pelletier, Maxime; Babin, Jérôme; Tremblay, Luc; Zhao, Yue

    2008-11-04

    Thermosensitive polymer micelles are generally obtained with block copolymers in which one block exhibits a lower critical solution temperature in aqueous solution. We investigate a different design that is based on the use of one block bearing a thermally labile side group, whose hydrolysis upon heating shifts the hydrophilic-hydrophobic balance toward the destabilization of block copolymer micelles. Atom transfer radical polymerization was utilized to synthesize a series of diblock copolymers composed of hydrophilic poly(ethylene oxide) (PEO) and hydrophobic poly(2-tetrahydropyranyl methacrylate) (PTHPMA). We show that micelles of PEO-b-PTHPMA in aqueous solution can be destabilized as a result of the thermosensitive hydrolytic cleavage of tetrahydropyranyl (THP) groups that transforms PTHPMA into hydrophilic poly(methacrylic acid). The three related processes occurring in aqueous solution, namely, hydrolytic cleavage of THP, destabilization of micelles, and release of loaded Nile Red (NR), were investigated simultaneously using 1H NMR, dynamic light scattering, and fluorescence spectroscopy, respectively. At 80 degrees C, the results suggest that the three events proceed with a similar kinetics. Although slower than at elevated temperatures, the disruption of PEO-b-PTHPMA micelles can take place at the body temperature (approximately 37 degrees C), and the release kinetics of NR can be adjusted by changing the relative lengths of the two blocks or the pH of the solution.

  11. Cold hypersensitivity increases with age in mice with sickle cell disease

    Science.gov (United States)

    Zappia, Katherine J.; Garrison, Sheldon R.; Hillery, Cheryl A.; Stucky, Cheryl L.

    2014-01-01

    Sickle cell disease (SCD) is associated with acute vaso-occlusive crises that trigger painful episodes and frequently involves ongoing, chronic pain. Additionally, both humans and mice with SCD experience heighted cold sensitivity. However, studies have not addressed the mechanism(s) underlying the cold sensitization, nor its progression with age. Here we measured thermotaxis behavior in young and aged mice with severe SCD. Sickle mice had a marked increase in cold sensitivity measured by a cold preference test. Further, cold hypersensitivity worsened with advanced age. We assessed whether enhanced peripheral input contributes to the chronic cold pain behavior by recording from C fibers, many of which are cold-sensitive, in skin-nerve preparations. We observed that C fibers from sickle mice displayed a shift to warmer (more sensitive) cold-detection thresholds. To address mechanisms underlying the cold sensitization in primary afferent neurons, we quantified mRNA expression levels for ion channels thought to be involved in cold detection. These included the Transient Receptor Potential Melastatin 8 (Trpm8) and TRP Ankyrin 1 (Trpa1) channels, as well as the two-pore domain potassium channels, TREK-1 (Kcnk2), TREK-2 (Kcnk4), and TRAAK (Kcnk10). Surprisingly, transcript expression levels of all of these channels were comparable between sickle and control mice. We further examined transcript expression of 83 additional pain-related genes and found increased mRNA levels for endothelin 1 and tachykinin receptor 1. These factors may contribute to hypersensitivity in sickle mice at both the afferent and behavioral levels. Sensory neurons from sickle cell disease mice are sensitized to cold, mirroring behavioral observations, and have increased expression of endothelin 1 and tachykinin receptor 1. PMID:24953902

  12. Electrically conductive gold nanoparticle-chitosan thermosensitive hydrogels for cardiac tissue engineering

    Energy Technology Data Exchange (ETDEWEB)

    Baei, Payam [Department of Stem Cells and Developmental Biology, Cell Science Research Center, Royan Institute for Stem Cell Biology and Technology, ACECR, Tehran (Iran, Islamic Republic of); Cardiovascular Engineering Laboratory, Faculty of Biomedical Engineering, Amirkabir University of Technology (Tehran Polytechnic), Tehran (Iran, Islamic Republic of); Jalili-Firoozinezhad, Sasan [Department of Biomedicine and Surgery, University Hospital Basel, University of Basel, Hebelstrasse 20, CH-4031 Basel (Switzerland); Department of Bioengineeringand IBB - Institute for Bioengineering and Biosciences, Instituto Superior Técnico, Universidade de Lisboa, Lisboa (Portugal); Rajabi-Zeleti, Sareh [Department of Stem Cells and Developmental Biology, Cell Science Research Center, Royan Institute for Stem Cell Biology and Technology, ACECR, Tehran (Iran, Islamic Republic of); Tafazzoli-Shadpour, Mohammad [Cardiovascular Engineering Laboratory, Faculty of Biomedical Engineering, Amirkabir University of Technology (Tehran Polytechnic), Tehran (Iran, Islamic Republic of); Baharvand, Hossein, E-mail: Baharvand@royaninstitute.org [Department of Stem Cells and Developmental Biology, Cell Science Research Center, Royan Institute for Stem Cell Biology and Technology, ACECR, Tehran (Iran, Islamic Republic of); Department of Developmental Biology, University of Science and Culture, ACECR, Tehran (Iran, Islamic Republic of); Aghdami, Nasser, E-mail: Nasser.Aghdami@royaninstitute.org [Department of Stem Cells and Developmental Biology, Cell Science Research Center, Royan Institute for Stem Cell Biology and Technology, ACECR, Tehran (Iran, Islamic Republic of)

    2016-06-01

    Injectable hydrogels that resemble electromechanical properties of the myocardium are crucial for cardiac tissue engineering prospects. We have developed a facile approach that uses chitosan (CS) to generate a thermosensitive conductive hydrogel with a highly porous network of interconnected pores. Gold nanoparticles (GNPs) were evenly dispersed throughout the CS matrix in order to provide electrical cues. The gelation response and electrical conductivity of the hydrogel were controlled by different concentrations of GNPs. The CS-GNP hydrogels were seeded with mesenchymal stem cells (MSCs) and cultivated for up to 14 days in the absence of electrical stimulations. CS-GNP scaffolds supported viability, metabolism, migration and proliferation of MSCs along with the development of uniform cellular constructs. Immunohistochemistry for early and mature cardiac markers showed enhanced cardiomyogenic differentiation of MSCs within the CS-GNP compared to the CS matrix alone. The results of this study demonstrate that incorporation of nanoscale electro-conductive GNPs into CS hydrogels enhances the properties of myocardial constructs. These constructs could find utilization for regeneration of other electroactive tissues. - Highlights: • Thermosensitive electro-conductive hydrogels were prepared from CS and GNPs. • Gelation time and conductivity were tuned by varying concentration of GNPs. • CS-2GNP with gelation time of 25.7 min and conductivity of 0.13 S·m{sup −1} was selected for in vitro studies. • CS-2GNP supported active metabolism, migration and proliferation of MSCs. • Expression of cardiac markers increased about two-fold in CS-2GNP compared to CS.

  13. Electrically conductive gold nanoparticle-chitosan thermosensitive hydrogels for cardiac tissue engineering

    International Nuclear Information System (INIS)

    Baei, Payam; Jalili-Firoozinezhad, Sasan; Rajabi-Zeleti, Sareh; Tafazzoli-Shadpour, Mohammad; Baharvand, Hossein; Aghdami, Nasser

    2016-01-01

    Injectable hydrogels that resemble electromechanical properties of the myocardium are crucial for cardiac tissue engineering prospects. We have developed a facile approach that uses chitosan (CS) to generate a thermosensitive conductive hydrogel with a highly porous network of interconnected pores. Gold nanoparticles (GNPs) were evenly dispersed throughout the CS matrix in order to provide electrical cues. The gelation response and electrical conductivity of the hydrogel were controlled by different concentrations of GNPs. The CS-GNP hydrogels were seeded with mesenchymal stem cells (MSCs) and cultivated for up to 14 days in the absence of electrical stimulations. CS-GNP scaffolds supported viability, metabolism, migration and proliferation of MSCs along with the development of uniform cellular constructs. Immunohistochemistry for early and mature cardiac markers showed enhanced cardiomyogenic differentiation of MSCs within the CS-GNP compared to the CS matrix alone. The results of this study demonstrate that incorporation of nanoscale electro-conductive GNPs into CS hydrogels enhances the properties of myocardial constructs. These constructs could find utilization for regeneration of other electroactive tissues. - Highlights: • Thermosensitive electro-conductive hydrogels were prepared from CS and GNPs. • Gelation time and conductivity were tuned by varying concentration of GNPs. • CS-2GNP with gelation time of 25.7 min and conductivity of 0.13 S·m"−"1 was selected for in vitro studies. • CS-2GNP supported active metabolism, migration and proliferation of MSCs. • Expression of cardiac markers increased about two-fold in CS-2GNP compared to CS.

  14. Thermo-sensitive polymer nanospheres as a smart plugging agent for shale gas drilling operations.

    Science.gov (United States)

    Wang, Wei-Ji; Qiu, Zheng-Song; Zhong, Han-Yi; Huang, Wei-An; Dai, Wen-Hao

    2017-01-01

    Emulsifier-free poly(methyl methacrylate-styrene) [P(MMA-St)] nanospheres with an average particle size of 100 nm were synthesized in an isopropyl alcohol-water medium by a solvothermal method. Then, through radical graft copolymerization of thermo-sensitive monomer N -isopropylacrylamide (NIPAm) and hydrophilic monomer acrylic acid (AA) onto the surface of P(MMA-St) nanospheres at 80 °C, a series of thermo-sensitive polymer nanospheres, named SD-SEAL with different lower critical solution temperatures (LCST), were prepared by adjusting the mole ratio of NIPAm to AA. The products were characterized by Fourier transform infrared spectroscopy, transmission electron microscopy, thermogravimetric analysis, particle size distribution, and specific surface area analysis. The temperature-sensitive behavior was studied by light transmittance tests, while the sealing performance was investigated by pressure transmission tests with Lungmachi Formation shales. The experimental results showed that the synthesized nanoparticles are sensitive to temperature and had apparent LCST values which increased with an increase in hydrophilic monomer AA. When the temperature was higher than its LCST value, SD-SEAL played a dual role of physical plugging and chemical inhibition, slowed down pressure transmission, and reduced shale permeability remarkably. The plugged layer of shale was changed to being hydrophobic, which greatly improved the shale stability.

  15. Neuronal involvement in cisplatin neuropathy

    DEFF Research Database (Denmark)

    Krarup-Hansen, A; Helweg-Larsen, Susanne Elisabeth; Schmalbruch, H

    2007-01-01

    of large dorsal root ganglion cells. Motor conduction studies, autonomic function and warm and cold temperature sensation remained unchanged at all doses of cisplatin treatment. The results of these studies are consistent with degeneration of large sensory neurons whereas there was no evidence of distal......Although it is well known that cisplatin causes a sensory neuropathy, the primary site of involvement is not established. The clinical symptoms localized in a stocking-glove distribution may be explained by a length dependent neuronopathy or by a distal axonopathy. To study whether the whole neuron...

  16. Zielgerichtete Chemotherapie solider Tumoren durch thermosensitive Liposomen in Kombination mit Doxorubicin, Gemcitabin und Mitomycin C

    OpenAIRE

    Limmer, Simone

    2014-01-01

    Auf DPPG2 basierende thermosensitive Liposomen (TSL) mit Hyperthermie (HT) induzierter zielgerichteter Wirkstofffreisetzung sind eine viel-versprechende Behandlungsstrategie in der Krebstherapie. TSL können als Wirkstoffträgersysteme die Zirkulationszeit und Anreicherung von Wirkstoffen im Zielgewebe erhöhen. Die vielfältigen Krebserkrankungen zeigen unterschiedliches Tumoransprechen auf die routinemäßig eingesetzten Zytostatika. Daher wäre es vorteilhaft, verschiedene Wirkstoffe in TSL e...

  17. Pharmacological blockade of the cold receptor TRPM8 attenuates autonomic and behavioral cold defenses and decreases deep body temperature.

    Science.gov (United States)

    Almeida, M Camila; Hew-Butler, Tamara; Soriano, Renato N; Rao, Sara; Wang, Weiya; Wang, Judy; Tamayo, Nuria; Oliveira, Daniela L; Nucci, Tatiane B; Aryal, Prafulla; Garami, Andras; Bautista, Diana; Gavva, Narender R; Romanovsky, Andrej A

    2012-02-08

    We studied N-(2-aminoethyl)-N-(4-(benzyloxy)-3-methoxybenzyl)thiophene-2-carboxamide hydrochloride (M8-B), a selective and potent antagonist of the transient receptor potential melastatin-8 (TRPM8) channel. In vitro, M8-B blocked cold-induced and TRPM8-agonist-induced activation of rat, human, and murine TRPM8 channels, including those on primary sensory neurons. In vivo, M8-B decreased deep body temperature (T(b)) in Trpm8(+/+) mice and rats, but not in Trpm8(-/-) mice, thus suggesting an on-target action. Intravenous administration of M8-B was more effective in decreasing T(b) in rats than intrathecal or intracerebroventricular administration, indicating a peripheral action. M8-B attenuated cold-induced c-Fos expression in the lateral parabrachial nucleus, thus indicating a site of action within the cutaneous cooling neural pathway to thermoeffectors, presumably on sensory neurons. A low intravenous dose of M8-B did not affect T(b) at either a constantly high or a constantly low ambient temperature (T(a)), but the same dose readily decreased T(b) if rats were kept at a high T(a) during the M8-B infusion and transferred to a low T(a) immediately thereafter. These data suggest that both a successful delivery of M8-B to the skin (high cutaneous perfusion) and the activation of cutaneous TRPM8 channels (by cold) are required for the hypothermic action of M8-B. At tail-skin temperatures cold) activation of TRPM8. M8-B affected all thermoeffectors studied (thermopreferendum, tail-skin vasoconstriction, and brown fat thermogenesis), thus suggesting that TRPM8 is a universal cold receptor in the thermoregulation system.

  18. Novel thermosensitive hydrogel for preventing formation of abdominal adhesions

    Directory of Open Access Journals (Sweden)

    Gao X

    2013-07-01

    Full Text Available Xiang Gao,1,2 Xiaohui Deng,3 Xiawei Wei,2 Huashan Shi,2 Fengtian Wang,2 Tinghong Ye,2 Bin Shao,2 Wen Nie,2 Yuli Li,2 Min Luo,2 Changyang Gong,2 Ning Huang1 1Department of Pathophysiology, College of Preclinical and Forensic Medical Sciences, Sichuan University, Chengdu, 2State Key Laboratory of Biotherapy and Cancer Center, West China Hospital, West China Medical School, Sichuan University, Chengdu, 3Department of Human Anatomy, Xinxiang Medical University, Xinxiang, People’s Republic of China Abstract: Adhesions can form after almost any type of abdominal surgery. Postoperative adhesions can be prevented by improved surgical techniques, such as reducing surgical trauma, preventing ischemia, and avoiding exposure of the peritoneal cavity to foreign materials. Although improved surgical techniques can potentially reduce formation of adhesions, they cannot be eliminated completely. Therefore, finding more effective methods to prevent postoperative adhesions is imperative. Recently, we found that a novel thermosensitive hydrogel, ie, poly(ε-caprolactone-poly(ethylene glycol-poly(ε-caprolactone (PCEC had the potential to prevent postoperative adhesions. Using the ring-opening polymerization method, we prepared a PCEC copolymer which could be dissolved and assembled at 55°C into PCEC micelles with mean size of 25 nm. At body temperature, a solution containing PCEC micelles could convert into a hydrogel. The PCEC copolymer was biodegradable and had low toxicity in vitro and in vivo. We found that most animals in a hydrogel-treated group (n = 10 did not develop adhesions. In contrast, 10 untreated animals developed adhesions that could only be separated by sharp dissection (P < 0.001. The hydrogel could adhere to peritoneal wounds and degraded gradually over 7–9 days, transforming into a viscous fluid that was completely absorbed within 12 days. The injured parietal and visceral peritoneum remesothelialized over about seven and nine days

  19. Cold suppresses agonist-induced activation of TRPV1.

    Science.gov (United States)

    Chung, M-K; Wang, S

    2011-09-01

    Cold therapy is frequently used to reduce pain and edema following acute injury or surgery such as tooth extraction. However, the neurobiological mechanisms of cold therapy are not completely understood. Transient receptor potential vanilloid 1 (TRPV1) is a capsaicin- and heat-gated nociceptive ion channel implicated in thermosensation and pathological pain under conditions of inflammation or injury. Although capsaicin-induced nociception, neuropeptide release, and ionic currents are suppressed by cold, it is not known if cold suppresses agonist-induced activation of recombinant TRPV1. We demonstrate that cold strongly suppressed the activation of recombinant TRPV1 by multiple agonists and capsaicin-evoked currents in trigeminal ganglia neurons under normal and phosphorylated conditions. Cold-induced suppression was partially impaired in a TRPV1 mutant that lacked heat-mediated activation and potentiation. These results suggest that cold-induced suppression of TRPV1 may share a common molecular basis with heat-induced potentiation, and that allosteric inhibition may contribute, in part, to the cold-induced suppression. We also show that combination of cold and a specific antagonist of TRPV1 can produce an additive suppression. Our results provide a mechanistic basis for cold therapy and may enhance anti-nociceptive approaches that target TRPV1 for managing pain under inflammation and tissue injury, including that from tooth extraction.

  20. Preparation of thermosensitive magnetic liposome encapsulated recombinant tissue plasminogen activator for targeted thrombolysis

    Energy Technology Data Exchange (ETDEWEB)

    Hsu, Hao-Lung [Department of Chemical and Materials Engineering, Chang Gung University, Kwei-San, Taoyuan 33302, Taiwan, ROC (China); Chen, Jyh-Ping, E-mail: jpchen@mail.cgu.edu.tw [Department of Chemical and Materials Engineering, Chang Gung University, Kwei-San, Taoyuan 33302, Taiwan, ROC (China); Department of Plastic and Reconstructive Surgery and Craniofacial Research Center, Chang Gung Memorial Hospital, Kwei-San, Taoyuan 33305, Taiwan, ROC (China); Graduate Institute of Health Industry and Technology, Research Center for Industry of Human Ecology, Chang Gung University of Science and Technology, Kwei-San, Taoyuan 33302, Taiwan, ROC (China); Department of Materials Engineering, Ming Chi University of Technology, Tai-Shan, New Taipei City 24301, Taiwan, ROC (China)

    2017-04-01

    Recombinant tissue plasminogen activator (rtPA) was encapsulated in thermosensitive magnetic liposome (TML) prepared from 1,2-dipalmitoyl-sn-glycero-3-phosphocholine, distearolyphosphatidyl ethanolamine-N-poly(ethylene glycol) 2000, cholesterol and Fe{sub 3}O{sub 4} magnetic nanoparticles by solvent evaporation/sonication and freeze-thaw cycles method. Response surface methodology was proved to be a powerful tool to predict the drug encapsulation efficiency and temperature-sensitive drug release. Validation experiments verified the accuracy of the model that provides a simple and effective method for fabricating TML with controllable encapsulation efficiency and predictable temperature-sensitive drug release behavior. The prepared samples were characterized for physico-chemical properties by dynamic light scattering, transmission electron microscopy, X-ray diffraction and differential scanning calorimetry. Temperature-sensitive release of rtPA could be confirmed from in vitro thrombolysis experiments. A thrombolytic drug delivery system using TML could be proposed for magnetic targeted delivery of rtPA to the site of thrombus followed by temperature-triggered controlled drug release in an alternating magnetic field. - Highlights: • rtPA and Fe{sub 3}O{sub 4} MNP were encapsulated in thermosensitive magnetic liposome (TML). • RSM could predict the drug encapsulation efficiency and temperature-sensitive drug release from TML. • Temperature-sensitive release of rtPA was confirmed from in vitro thrombolysis experiments. • TML-rtPA will be useful as a magnetic targeted nanodrug to improve clinical thrombolytic therapy.

  1. Direct effects of endogenous pyrogen on medullary temperature-responsive neurons in rabbits.

    Science.gov (United States)

    Sakata, Y; Morimoto, A; Takase, Y; Murakami, N

    1981-01-01

    The effect of endogenous pyrogen (E.P.) injected directly into the tissue near the recording site were examined on the activities of the medullary temperature-responsive (TR) neurons in rabbits anesthetized with urethane. Endogenous pyrogen prepared from rabbit's whole blood was administered by a fine glass cannula (100-200 micrometer in diameter) in a fluid volume of 1 to 4 microliter. The cannula was fixed to the manipulator in parallel with a microelectrode and their tips were less than 0.05 mm apart. In rabbits with the intact preoptic/anterior hypothalamic (PO/AH) region, 4 warm-responsive neurons out of 7 were inhibited and 6 cold-responsive neuron out of 7 were excited by the direct administration of the E.P. In rabbits with lesions of the PO/AH, 5 warm-responsive neurons out of 9 were inhibited and 6 cold-responsive neurons out of 8 were facilitated by E.P. Antipyretics administered locally after the E.P. antagonized the pyretic effect, causing a return of the discharge of TR neuron to the control rate within 2.4 +/- 1.2 (mean +/- S.D.) min. The medullary TR neuron itself has the ability to respond to the E.P. and contributes to the development of fever.

  2. Hypoxia-inducible factor 1 regulates heat and cold pain sensitivity and persistence.

    Science.gov (United States)

    Kanngiesser, Maike; Mair, Norbert; Lim, Hee-Young; Zschiebsch, Katja; Blees, Johanna; Häussler, Annett; Brüne, Bernhard; Ferreiròs, Nerea; Kress, Michaela; Tegeder, Irmgard

    2014-06-01

    The present study assessed the functions of the transcription factor hypoxia-inducible factor (HIF) in sensory neurons in models of acute, inflammatory, ischemic, and neuropathic pain. The alpha subunit, HIF1α, was specifically deleted in neurons of the dorsal root ganglia by mating HIF1α(fl/fl) mice with SNScre mice. SNS-HIF1α(-/-) mice were more sensitive to noxious heat and cold pain stimulation than were HIF1α(fl/fl) control mice. They also showed heightened first-phase nociceptive responses in the formalin and capsaicin tests with increased numbers of cFos-positive neurons in the dorsal horn, and intensified hyperalgesia in early phases after paw inflammation and hind limb ischemia/reperfusion. The behavioral cold and heat pain hypersensitivity was explained by increased calcium fluxes after transient receptor potential channel activation in primary sensory neurons of SNS-HIF1α(-/-) mice and lowered electrical activation thresholds of sensory fibers. SNS-HIF1α(-/-) mice however, developed less neuropathic pain after sciatic nerve injury, which was associated with an abrogation of HIF1-mediated gene up-regulation. The results suggest that HIF1α is protective in terms of acute heat and cold pain but in case of ongoing activation in injured neurons, it may promote the development of neuropathic pain. The duality of HIF1 in pain regulation may have an impact on the side effects of drugs targeting HIF1, which are being developed, for example, as anticancer agents. Specifically, in patients with cancer neuropathy, however, temporary HIF1 inhibition might provide a welcome combination of growth and pain reduction.

  3. Neuronal hyperexcitability in the ventral posterior thalamus of neuropathic rats: modality selective effects of pregabalin.

    Science.gov (United States)

    Patel, Ryan; Dickenson, Anthony H

    2016-07-01

    Neuropathic pain represents a substantial clinical challenge; understanding the underlying neural mechanisms and back-translation of therapeutics could aid targeting of treatments more effectively. The ventral posterior thalamus (VP) is the major termination site for the spinothalamic tract and relays nociceptive activity to the somatosensory cortex; however, under neuropathic conditions, it is unclear how hyperexcitability of spinal neurons converges onto thalamic relays. This study aimed to identify neural substrates of hypersensitivity and the influence of pregabalin on central processing. In vivo electrophysiology was performed to record from VP wide dynamic range (WDR) and nociceptive-specific (NS) neurons in anesthetized spinal nerve-ligated (SNL), sham-operated, and naive rats. In neuropathic rats, WDR neurons had elevated evoked responses to low- and high-intensity punctate mechanical stimuli, dynamic brushing, and innocuous and noxious cooling, but less so to heat stimulation, of the receptive field. NS neurons in SNL rats also displayed increased responses to noxious punctate mechanical stimulation, dynamic brushing, noxious cooling, and noxious heat. Additionally, WDR, but not NS, neurons in SNL rats exhibited substantially higher rates of spontaneous firing, which may correlate with ongoing pain. The ratio of WDR-to-NS neurons was comparable between SNL and naive/sham groups, suggesting relatively few NS neurons gain sensitivity to low-intensity stimuli leading to a "WDR phenotype." After neuropathy was induced, the proportion of cold-sensitive WDR and NS neurons increased, supporting the suggestion that changes in frequency-dependent firing and population coding underlie cold hypersensitivity. In SNL rats, pregabalin inhibited mechanical and heat responses but not cold-evoked or elevated spontaneous activity. Copyright © 2016 the American Physiological Society.

  4. Enabling Junction Temperature Estimation via Collector-Side Thermo-Sensitive Electrical Parameters through Emitter Stray Inductance in High-Power IGBT Modules

    DEFF Research Database (Denmark)

    Luo, Haoze; Li, Wuhua; Iannuzzo, Francesco

    2018-01-01

    This paper proposes the adoption of the inherent emitter stray inductance LeE in high-power insulated gate bipolar transistor (IGBT) modules as a new dynamic thermo-sensitive electrical parameter (d-TSEP). Furthermore, a family of 14 derived dynamic TSEP candidates has been extracted and classified...

  5. Applications of chitosan-based thermo-sensitive copolymers for harvesting living cell sheet

    International Nuclear Information System (INIS)

    Chen, J.-P.; Yang, T.-F.

    2008-01-01

    A thermo-sensitive chitosan-based copolymer hydrogel was used for harvesting living cell sheets. The hydrogel was tested for harvesting 3T3 cells after carrying out cell culture at 37 deg. C and incubating the confluent cells at 20 deg. C for spontaneous detachment of cell sheets from hydrogel surface without enzyme treatment. Results from cell viability assay and microscopy observations demonstrated that cells could attach to the hydrogel surface and maintain high viability and proliferation ability. Cell detachment efficiency from the hydrogel was about 80%. The detached cell sheet retained high viability and could proliferate again after transferred to a new culture surface

  6. Experimental evidence of temperature gradients in cavitating microflows seeded with thermosensitive nanoprobes

    Science.gov (United States)

    Ayela, Frédéric; Medrano-Muñoz, Manuel; Amans, David; Dujardin, Christophe; Brichart, Thomas; Martini, Matteo; Tillement, Olivier; Ledoux, Gilles

    2013-10-01

    Thermosensitive fluorescent nanoparticles seeded in deionized water combined with confocal microscopy enables thermal mapping over three dimensions of the liquid phase flowing through a microchannel interrupted by a microdiaphragm. This experiment reveals the presence of a strong thermal gradient up to ˜105 K/m only when hydrodynamic cavitation is present. Here hydrodynamic cavitation is the consequence of high shear rates downstream in the diaphragm. This temperature gradient is located in vortical structures associated with eddies in the shear layers. We attribute such overheating to the dissipation involved by the cavitating flow regime. Accordingly, we demonstrate that the microsizes of the device enhance the intensity of the thermal gap.

  7. Sensitization of capsaicin and icilin responses in oxaliplatin treated adult rat DRG neurons

    Directory of Open Access Journals (Sweden)

    Anand Praveen

    2010-11-01

    Full Text Available Abstract Background Oxaliplatin chemotherapy induced neuropathy is a dose related cumulative toxicity that manifests as tingling, numbness, and chronic pain, compromising the quality of life and leading to discontinued chemotherapy. Patients report marked hypersensitivity to cold stimuli at early stages of treatment, when sensory testing reveals cold and heat hyperalgesia. This study examined the morphological and functional effects of oxaliplatin treatment in cultured adult rat DRG neurons. Results 48 hour exposure to oxaliplatin resulted in dose related reduction in neurite length, density, and number of neurons compared to vehicle treated controls, using Gap43 immunostaining. Neurons treated acutely with 20 μg/ml oxaliplatin showed significantly higher signal intensity for cyclic AMP immunofluorescence (160.5 ± 13 a.u., n = 3, P Conclusions Oxaliplatin treatment induces TRP sensitization mediated by increased intracellular cAMP, which may cause neuronal damage. These effects may be mitigated by co-treatment with adenylyl cyclase inhibitors, like CB2 agonists, to alleviate the neurotoxic effects of oxaliplatin.

  8. Three-Dimensional Scaffold Chip with Thermosensitive Coating for Capture and Reversible Release of Individual and Cluster of Circulating Tumor Cells.

    Science.gov (United States)

    Cheng, Shi-Bo; Xie, Min; Chen, Yan; Xiong, Jun; Liu, Ya; Chen, Zhen; Guo, Shan; Shu, Ying; Wang, Ming; Yuan, Bi-Feng; Dong, Wei-Guo; Huang, Wei-Hua

    2017-08-01

    Tumor metastasis is attributed to circulating tumor cells (CTC) or CTC clusters. Many strategies have hitherto been designed to isolate CTCs, but there are few methods that can capture and gently release CTC clusters as efficient as single CTCs. Herein, we developed a three-dimensional (3D) scaffold chip with thermosensitive coating for high-efficiency capture and release of individual and cluster CTCs. The 3D scaffold chip successfully combines the specific recognition and physically obstructed effect of 3D scaffold structure to significantly improve cell clusters capture efficiency. Thermosensitive gelatin hydrogel uniformly coated on the scaffold dissolves at 37 °C quickly, and the captured cells are gently released from chip with high viability. Notably, this platform was applied to isolate CTCs from cancer patients' blood samples. This allows global DNA and RNA methylation analysis of collected single CTC and CTC clusters, indicating the great potential of this platform in cancer diagnosis and downstream analysis at the molecular level.

  9. Genes associated with thermosensitive genic male sterility in rice identified by comparative expression profiling.

    Science.gov (United States)

    Pan, Yufang; Li, Qiaofeng; Wang, Zhizheng; Wang, Yang; Ma, Rui; Zhu, Lili; He, Guangcun; Chen, Rongzhi

    2014-12-16

    Thermosensitive genic male sterile (TGMS) lines and photoperiod-sensitive genic male sterile (PGMS) lines have been successfully used in hybridization to improve rice yields. However, the molecular mechanisms underlying male sterility transitions in most PGMS/TGMS rice lines are unclear. In the recently developed TGMS-Co27 line, the male sterility is based on co-suppression of a UDP-glucose pyrophosphorylase gene (Ugp1), but further study is needed to fully elucidate the molecular mechanisms involved. Microarray-based transcriptome profiling of TGMS-Co27 and wild-type Hejiang 19 (H1493) plants grown at high and low temperatures revealed that 15462 probe sets representing 8303 genes were differentially expressed in the two lines, under the two conditions, or both. Environmental factors strongly affected global gene expression. Some genes important for pollen development were strongly repressed in TGMS-Co27 at high temperature. More significantly, series-cluster analysis of differentially expressed genes (DEGs) between TGMS-Co27 plants grown under the two conditions showed that low temperature induced the expression of a gene cluster. This cluster was found to be essential for sterility transition. It includes many meiosis stage-related genes that are probably important for thermosensitive male sterility in TGMS-Co27, inter alia: Arg/Ser-rich domain (RS)-containing zinc finger proteins, polypyrimidine tract-binding proteins (PTBs), DEAD/DEAH box RNA helicases, ZOS (C2H2 zinc finger proteins of Oryza sativa), at least one polyadenylate-binding protein and some other RNA recognition motif (RRM) domain-containing proteins involved in post-transcriptional processes, eukaryotic initiation factor 5B (eIF5B), ribosomal proteins (L37, L1p/L10e, L27 and L24), aminoacyl-tRNA synthetases (ARSs), eukaryotic elongation factor Tu (eEF-Tu) and a peptide chain release factor protein involved in translation. The differential expression of 12 DEGs that are important for pollen

  10. Intra-articular Administration of Chitosan Thermosensitive In Situ Hydrogels Combined With Diclofenac Sodium-Loaded Alginate Microspheres.

    Science.gov (United States)

    Qi, Xiaole; Qin, Xiaoxue; Yang, Rong; Qin, Jiayi; Li, Wenyan; Luan, Kun; Wu, Zhenghong; Song, Li

    2016-01-01

    The aims of this study were to prepare fine intra-articular-administrated chitosan thermosensitive hydrogels combined with alginate microspheres and to investigate the possibility of those hydrogels as a drug delivery system for promoting the anti-inflammation effect. Diclofenac sodium containing alginate microspheres was prepared by a modified emulsification and/or gelation method and then dispersed into injectable thermosensitive hydrogels, consisting of chitosan and β-glycerophosphate. The final combined hydrogels were evaluated in terms of their morphology properties, rheological properties, in vitro drug release, and in vivo biocompatibility and pharmacodynamics behaviors. The optimized formulation exhibited sol-gel transition at 31.72 ± 0.42°C and quickly turned into gel within 5 min, with sustained drug release characteristics followed Ritger-Peppas equation, which could prolong the in vitro drug release to 5 days. In addition, the anti-inflammation efficacy of the combined hydrogels in rabbits with experimental rheumatoid arthritis was higher than that of drug solution and pure chitosan hydrogels. Those results demonstrated that these combined hydrogels could become a potential drug delivery system for improving the therapeutic effect of diclofenac sodium and suggested an important technology platform for intra-articular administration. Copyright © 2016 American Pharmacists Association®. Published by Elsevier Inc. All rights reserved.

  11. Thermo-sensitively and magnetically ordered mesoporous carbon nanospheres for targeted controlled drug release and hyperthermia application.

    Science.gov (United States)

    Chen, Lin; Zhang, Huan; Zheng, Jing; Yu, Shiping; Du, Jinglei; Yang, Yongzhen; Liu, Xuguang

    2018-03-01

    A multifunctional nanoplatform based on thermo-sensitively and magnetically ordered mesoporous carbon nanospheres (TMOMCNs) is developed for effective targeted controlled release of doxorubicin hydrochloride (DOX) and hyperthermia in this work. The morphology, specific surface area, porosity, thermo-stability, thermo-sensitivity, as well as magnetism properties of TMOMCNs were verified by high resolution transmission electron microscopy, field emission scanning electron microscopy, thermo-gravimetric analysis, X-ray diffraction, Brunauer-Emmeltt-Teller surface area analysis, dynamic light scattering and vibrating sample magnetometry measurement. The results indicate that TMOMCNs have an average diameter of ~146nm with a lower critical solution temperature at around 39.5°C. They are superparamagnetic with a magnetization of 10.15emu/g at 20kOe. They generate heat when inductive magnetic field is applied to them and have a normalized specific absorption rate of 30.23W/g at 230kHz and 290Oe, showing good potential for hyperthermia. The DOX loading and release results illustrate that the loading capacity is 135.10mg/g and release performance could be regulated by changing pH and temperature. The good targeting, DOX loading and release and hyperthermia properties of TMOMCNs offer new probabilities for high effectiveness and low toxicity of cancer chemotherapy. Copyright © 2017 Elsevier B.V. All rights reserved.

  12. Custom-designed Laser-based Heating Apparatus for Triggered Release of Cisplatin from Thermosensitive Liposomes with Magnetic Resonance Image Guidance.

    Science.gov (United States)

    Dou, Yannan N; Weersink, Robert A; Foltz, Warren D; Zheng, Jinzi; Chaudary, Naz; Jaffray, David A; Allen, Christine

    2015-12-13

    Liposomes have been employed as drug delivery systems to target solid tumors through exploitation of the enhanced permeability and retention (EPR) effect resulting in significant reductions in systemic toxicity. Nonetheless, insufficient release of encapsulated drug from liposomes has limited their clinical efficacy. Temperature-sensitive liposomes have been engineered to provide site-specific release of drug in order to overcome the problem of limited tumor drug bioavailability. Our lab has designed and developed a heat-activated thermosensitive liposome formulation of cisplatin (CDDP), known as HTLC, to provide triggered release of CDDP at solid tumors. Heat-activated delivery in vivo was achieved in murine models using a custom-built laser-based heating apparatus that provides a conformal heating pattern at the tumor site as confirmed by MR thermometry (MRT). A fiber optic temperature monitoring device was used to measure the temperature in real-time during the entire heating period with online adjustment of heat delivery by alternating the laser power. Drug delivery was optimized under magnetic resonance (MR) image guidance by co-encapsulation of an MR contrast agent (i.e., gadoteridol) along with CDDP into the thermosensitive liposomes as a means to validate the heating protocol and to assess tumor accumulation. The heating protocol consisted of a preheating period of 5 min prior to administration of HTLC and 20 min heating post-injection. This heating protocol resulted in effective release of the encapsulated agents with the highest MR signal change observed in the heated tumor in comparison to the unheated tumor and muscle. This study demonstrated the successful application of the laser-based heating apparatus for preclinical thermosensitive liposome development and the importance of MR-guided validation of the heating protocol for optimization of drug delivery.

  13. Arginine vasopressin antagonizes the effects of prostaglandin E2 on the spontaneous activity of warm-sensitive and temperature-insensitive neurons in the medial preoptic area in rats.

    Science.gov (United States)

    Xu, Jian-Hui; Hou, Xiao-Yu; Tang, Yu; Luo, Rong; Zhang, Jie; Liu, Chang; Yang, Yong-Lu

    2018-01-01

    Arginine vasopressin (AVP) plays an important role in thermoregulation and antipyresis. We have demonstrated that AVP could change the spontaneous activity of thermosensitive and temperature insensitive neurons in the preoptic area. However, whether AVP influences the effects of prostaglandin E 2 (PGE 2 ) on the spontaneous activity of neurons in the medial preoptic area (MPO) remains unclear. Our experiment showed that PGE 2 decreased the spontaneous activity of warm-sensitive neurons, and increased that of low-slope temperature-insensitive neurons in the MPO. AVP attenuated the inhibitory effect of PGE 2 on warm-sensitive neurons, and reversed the excitatory effect of PGE 2 on low-slope temperature-insensitive neurons, demonstrating that AVP antagonized the effects of PGE 2 on the spontaneous activity of these neurons. The effect of AVP was suppressed by an AVP V 1a receptor antagonist, suggesting that V 1a receptor mediated the action of AVP. We also demonstrated that AVP attenuated the PGE 2 -induced decrease in the prepotential's rate of rise in warm-sensitive neurons and the PGE 2 -induced increase in that in low-slope temperature-insensitive neurons through the V 1a receptor. Together, these data indicated that AVP antagonized the PGE 2 -induced change in the spontaneous activity of warm-sensitive and low-slope temperature-insensitive neurons in the MPO partly by reducing the PGE 2 -induced change in the prepotential of these neurons in a V 1a receptor-dependent manner. Copyright © 2017 Elsevier B.V. All rights reserved.

  14. Thermosensitive Behavior and Antibacterial Activity of Cotton Fabric Modified with a Chitosan-poly(N-isopropylacrylamide Interpenetrating Polymer Network Hydrogel

    Directory of Open Access Journals (Sweden)

    Boxiang Wang

    2016-03-01

    Full Text Available To increase the themosensitive behavior and antibacterial activity of cotton fabric, a series of poly (N-isopropylacrylamide/chitosan (PNIPAAm/Cs hydrogels was synthesized by interpenetrating polymer network (IPN technology using a redox initiator. The IPN PNIPAAm/Cs hydrogel was characterized by Fourier transform infrared spectroscopy (FT-IR, differential scanning calorimetry (DSC, and thermogravimetric analysis (TGA. The results indicated that the IPN PNIPAAm/Cs hydrogel has a lower critical solution temperature (LCST at 33 °C. The IPN hydrogel was then used to modify cotton fabric using glutaric dialdehyde (GA as a crosslinking agent following a double-dip-double-nip process. The results demonstrated that the modified cotton fabric showed obvious thermosensitive behavior and antibacterial activity. The contact angle of the modified cotton fabric has a sharp rise around 33 °C, and the modified cotton fabric showed an obvious thermosensitive behavior. The bacterial reduction of modified cotton fabric against Staphylococcus aureus (S. aureus and Escherichia coli (E. coli were more than 99%. This study presents a valuable route towards smart textiles and their applications in functional clothing.

  15. Abnormal activity of corneal cold thermoreceptors underlies the unpleasant sensations in dry eye disease.

    Science.gov (United States)

    Kovács, Illés; Luna, Carolina; Quirce, Susana; Mizerska, Kamila; Callejo, Gerard; Riestra, Ana; Fernández-Sánchez, Laura; Meseguer, Victor M; Cuenca, Nicolás; Merayo-Lloves, Jesús; Acosta, M Carmen; Gasull, Xavier; Belmonte, Carlos; Gallar, Juana

    2016-02-01

    Dry eye disease (DED) affects >10% of the population worldwide, and it provokes an unpleasant sensation of ocular dryness, whose underlying neural mechanisms remain unknown. Removal of the main lachrymal gland in guinea pigs caused long-term reduction of basal tearing accompanied by changes in the architecture and density of subbasal corneal nerves and epithelial terminals. After 4 weeks, ongoing impulse activity and responses to cooling of corneal cold thermoreceptor endings were enhanced. Menthol (200 μM) first excited and then inactivated this augmented spontaneous and cold-evoked activity. Comparatively, corneal polymodal nociceptors of tear-deficient eyes remained silent and exhibited only a mild sensitization to acidic stimulation, whereas mechanonociceptors were not affected. Dryness-induced changes in peripheral cold thermoreceptor responsiveness developed in parallel with a progressive excitability enhancement of corneal cold trigeminal ganglion neurons, primarily due to an increase of sodium currents and a decrease of potassium currents. In corneal polymodal nociceptor neurons, sodium currents were enhanced whereas potassium currents remain unaltered. In healthy humans, exposure of the eye surface to menthol vapors or to cold air currents evoked unpleasant sensations accompanied by increased blinking frequency that we attributed to cold thermoreceptor stimulation. Notably, stimulation with menthol reduced the ongoing background discomfort of patients with DED, conceivably due to use-dependent inactivation of cold thermoreceptors. Together, these data indicate that cold thermoreceptors contribute importantly to the detection and signaling of ocular surface wetness, and develop under chronic eye dryness conditions an injury-evoked neuropathic firing that seems to underlie the unpleasant sensations experienced by patients with DED.

  16. Successful in vivo hyperthermal therapy toward breast cancer by Chinese medicine shikonin-loaded thermosensitive micelle

    Directory of Open Access Journals (Sweden)

    Su Y

    2017-05-01

    Full Text Available Yonghua Su,1,* Nian Huang,1,* Di Chen,2,* Li Zhang,2,* Xia Dong,2 Yun Sun,2 Xiandi Zhu,2 Fulei Zhang,2 Jie Gao,2 Ying Wang,2 Kexing Fan,2 Puichi Lo,3 Wei Li,2 Changquan Ling1 1Department of Integrative Oncology, Changhai Hospital of Traditional Chinese Medicine, 2International Joint Cancer Institute, The Second Military Medical University, Shanghai, 3Department of Biomedical Sciences, City University of Hong Kong, Kowloon Tong, Hong Kong, China *These authors contributed equally to this work Abstract: The Chinese traditional medicine Shikonin is an ideal drug due to its multiple targets to tumor cells. But in clinics, improving its aqueous solubility and tumor accumulation is still a challenge. Herein, a copolymer with tunable poly(N-isopropylacrymaide and polylactic acid block lengths is designed, synthesized, and characterized in nuclear magnetic resonance. The corresponding thermosensitive nanomicelle (TN with well-defined core-shell structure is then assembled in an aqueous solution. For promoting the therapeutic index, the physical-chemistry properties of TNs including narrow size, low critical micellar concentration, high serum stability, tunable volume phase transition temperature (VPTT, high drug-loading capacity, and temperature-controlled drug release are systematically investigated and regulated through the fine self-assembly. The shikonin is then entrapped in a degradable inner core resulting in a shikonin-loaded thermosensitive nanomicelle (STN with a VPTT of ~40°C. Compared with small-molecular shikonin, the in vitro cellular internalization and cytotoxicity of STN against breast cancer cells (Michigan Cancer Foundation-7 are obviously enhanced. In addition, the therapeutic effect is further enhanced by the programmed cell death (PCD specifically evoked by shikonin. Interestingly, both the proliferation inhibition and PCD are synergistically promoted as T > VPTT, namely the temperature-regulated passive targeting. Consequently, as

  17. Strengthening injectable thermo-sensitive NIPAAm-g-chitosan hydrogels using chemical cross-linking of disulfide bonds as scaffolds for tissue engineering.

    Science.gov (United States)

    Wu, Shu-Wei; Liu, Xifeng; Miller, A Lee; Cheng, Yu-Shiuan; Yeh, Ming-Long; Lu, Lichun

    2018-07-15

    In the present study, we fabricated non-toxic, injectable, and thermo-sensitive NIPAAm-g-chitosan (NC) hydrogels with thiol modification for introduction of disulfide cross-linking strategy. Previously, NIPAAm and chitosan copolymer has been proven to have excellent biocompatibility, biodegradability and rapid phase transition after injection, suitable to serve as cell carriers or implanted scaffolds. However, weak mechanical properties significantly limit their potential for biomedical fields. In order to overcome this issue, we incorporated thiol side chains into chitosan by covalently conjugating N-acetyl-cysteine (NAC) with carbodiimide chemistry to strengthen mechanical properties. After oxidation of thiols into disulfide bonds, modified NC hydrogels did improve the compressive modulus over 9 folds (11.4 kPa). Oscillatory frequency sweep showed a positive correlation between storage modulus and cross-liking density as well. Additionally, there was no cytotoxicity observed to mesenchymal stem cells, fibroblasts and osteoblasts. We suggested that the thiol-modified thermo-sensitive polysaccharide hydrogels are promising to be a cell-laden biomaterial for tissue regeneration. Copyright © 2018 Elsevier Ltd. All rights reserved.

  18. DEG/ENaC ion channels involved in sensory transduction are modulated by cold temperature

    Science.gov (United States)

    Askwith, Candice C.; Benson, Christopher J.; Welsh, Michael J.; Snyder, Peter M.

    2001-01-01

    Several DEG/ENaC cation channel subunits are expressed in the tongue and in cutaneous sensory neurons, where they are postulated to function as receptors for salt and sour taste and for touch. Because these tissues are exposed to large temperature variations, we examined how temperature affects DEG/ENaC channel function. We found that cold temperature markedly increased the constitutively active Na+ currents generated by epithelial Na+ channels (ENaC). Half-maximal stimulation occurred at 25°C. Cold temperature did not induce current from other DEG/ENaC family members (BNC1, ASIC, and DRASIC). However, when these channels were activated by acid, cold temperature potentiated the currents by slowing the rate of desensitization. Potentiation was abolished by a “Deg” mutation that alters channel gating. Temperature changes in the physiologic range had prominent effects on current in cells heterologously expressing acid-gated DEG/ENaC channels, as well as in dorsal root ganglion sensory neurons. The finding that cold temperature modulates DEG/ENaC channel function may provide a molecular explanation for the widely recognized ability of temperature to modify taste sensation and mechanosensation. PMID:11353858

  19. The effects of prostaglandin E2 on the firing rate activity of thermosensitive and temperature insensitive neurons in the ventromedial preoptic area of the rat hypothalamus.

    Science.gov (United States)

    Ranels, Heather J; Griffin, John D

    2003-02-21

    In response to an immune system challenge with lipopolysaccharide (LPS), recent work has shown that Fos immunoreactivity is displayed by neurons in the ventromedial preoptic area of the hypothalamus (VMPO). In addition, neurons in this region show distinct axonal projections to the anterior perifornical area (APFx) and the paraventricular nucleus (PVN). It has been hypothesized that neurons within the VMPO integrate their local responses to temperature with changes in firing activity that result from LPS induced production of prostaglandin E(2) (PGE(2)). This may be an important mechanism by which the set-point regulation of thermoeffector neurons in the APFx and PVN is altered, resulting in hyperthermia. To characterize the firing rate activity of VMPO neurons, single-unit recordings were made of neuronal extracellular activity in rat hypothalamic tissue slices. Based on the slope of firing rate as a function of tissue temperature, neurons were classified as either warm sensitive or temperature insensitive. Neurons were then treated with PGE(2) (200 nM) while tissue temperature was held at a constant level ( approximately 36 degrees C). The majority of temperature insensitive neurons responded to PGE(2) with an increase in firing rate activity, while warm sensitive neurons showed a reduction in firing rate. This suggests that both warm sensitive and temperature insensitive neurons in the VMPO may play critical and contrasting roles in the production of a fever during an acute phase response to infection.

  20. Multimodal targeted high relaxivity thermosensitive liposome for in vivo imaging

    Science.gov (United States)

    Kuijten, Maayke M. P.; Hannah Degeling, M.; Chen, John W.; Wojtkiewicz, Gregory; Waterman, Peter; Weissleder, Ralph; Azzi, Jamil; Nicolay, Klaas; Tannous, Bakhos A.

    2015-11-01

    Liposomes are spherical, self-closed structures formed by lipid bilayers that can encapsulate drugs and/or imaging agents in their hydrophilic core or within their membrane moiety, making them suitable delivery vehicles. We have synthesized a new liposome containing gadolinium-DOTA lipid bilayer, as a targeting multimodal molecular imaging agent for magnetic resonance and optical imaging. We showed that this liposome has a much higher molar relaxivities r1 and r2 compared to a more conventional liposome containing gadolinium-DTPA-BSA lipid. By incorporating both gadolinium and rhodamine in the lipid bilayer as well as biotin on its surface, we used this agent for multimodal imaging and targeting of tumors through the strong biotin-streptavidin interaction. Since this new liposome is thermosensitive, it can be used for ultrasound-mediated drug delivery at specific sites, such as tumors, and can be guided by magnetic resonance imaging.

  1. Synthesis and characterization of a thermo-sensitive poly( N-methyl acryloylglycine methyl ester) used as a drug release carrier

    Science.gov (United States)

    Deng, Kui-Lin; Zhong, Hai-Bin; Jiao, Yi-Suo; Fan, Ting; Qiao, Xiao; Zhang, Peng-Fei; Ren, Xiao-Bo

    2010-06-01

    In this article, poly( N-methyl acryloylglycine methyl ester) (PNMAME) was prepared as a novel thermosensitive material with a lower critical solution temperature (LCST) at around 49.5°C. The chemical structures of the monomer NMAME and PNMAME were characterized by 1H NMR and IR measurements. The LCST was investigated systematically as a function of PNMAME concentration, inorganic salt solution and pH value. The results indicated that LCST of PNMAME was obviously dependent on PNMAME concentration and pH. The LCST was increased with a decrease in pH value and PNMAME concentration. To obtain a thermo-sensitive hydrogel with the phase transition temperature close to human body temperature, the copolymerization was conducted between NMAME and N-acryloylglycine ethyl ester (NAGEE). The release behavior of caffeine was evaluated at different temperatures and contents of cross-linkers ( N, N-methylenebis(acrylamide) (NMBA)). The increase of cross-linker content led to a decrease in the release rate of caffeine due to higher crossing density in the hydrogel network. In addition, a faster release of caffeine from the hydrogel with 3% NMBA at 37°C was found in contrast to that at 18°C.

  2. Preparation and Evaluation of Oxaliplatin Thermosensitive Liposomes with Rapid Release and High Stability.

    Directory of Open Access Journals (Sweden)

    Chunying Zeng

    Full Text Available Oxaliplatin (OXP was reported to show low anti-tumor activity when used alone and to display side effects; this low activity was attributed to high partitioning to erythrocytes and low accumulation in tumors. Thermosensitive liposomes (TSL were considered able to specifically deliver drugs to heated tumors and to resolve the OXP distribution problem. Regretfully, TSL encapsulating doxorubicin did not demonstrate significant improvement in progression-free survival. Drug release below 41°C and significant leakage were considered major reasons for the failure. The purpose of this study was to acquire OXP TSL with rapid release at the triggered temperature and high stability at body temperature and at storage temperatures. A small quantity of poloxamer 188 was introduced into the TSL formulation to stabilize the encapsulated drug. It was shown that the addition of poloxamer 188 had no influence on the TSL characteristics. More than 90% of OXP was released within 10 min at 42°C, and less than 15% was released within 60 min at temperatures below 39°C. TSL were stable at 37°C for 96 h and at 4°C for 6 months. The anti-tumor activity of TSL at the dose of 2.5 mg/kg was certified to be equal to those of OXP injection and non-thermosensitive liposomes (NTSL at the dose of 5 mg/kg, and significant improvement of tumor inhibition was observed in TSL compared with injection and NTSL at the same dose. It was also shown from the histological transmutation of tumors that TSL had stronger anti-tumor activity. Therefore, it could be concluded that TSL composed of a proper amount of poloxamer had rapid release and high stability, and OXP TSL would be anticipated to exert prominent anti-tumor activity in the clinic.

  3. The influence of low process temperature on the hydrodynamic radius of polyNIPAM-co-PEG thermosensitive nanoparticles presumed as drug carriers for bioactive proteins

    Czech Academy of Sciences Publication Activity Database

    Musial, W.; Michálek, Jiří

    2015-01-01

    Roč. 72, č. 1 (2015), s. 161-169 ISSN 0001-6837 Institutional support: RVO:61389013 Keywords : nanogel * N-isopropylacrylamide * thermosensitivity Subject RIV: CD - Macromolecular Chemistry Impact factor: 0.877, year: 2015 http://www.ptfarm.pl/pub/File/Acta_Poloniae/2015/1/161.pdf

  4. A thermo-sensitive purple leaf rice mutant--PLM12 and its genetical study

    International Nuclear Information System (INIS)

    Wu Guanting; Wang Xianyu; Jin Wei

    2001-01-01

    PLM12 was a thermo-sensitive purple leaf mutant selected from Indica rice variety Luqingzao 1 treated with pingyangmycin in combination with γ-rays, and for display of its mutant character, a relatively high temperature was required. Compared with its original parent, many major agronomic traits of PLM12 changed to varied extents. Based on spikelet cutting experiment, it was believed that significant decreases in number of filled grains per panicle, fertility, and 1000-grain weight in PLM12 resulted mainly from a great decline in photosynthetic capacity and serious lack of photosynthate in purple leaves. It was indicated by genetic analysis that expression of the mutant phenotype in PLM12 was conditioned by a single recessive major nuclear gene and modified by several minor genes

  5. Motor impairment and neuronal damage following hypothermia in tropical amphibians.

    Science.gov (United States)

    Daló, Nelson L; Bracho, Gustavo A; Piña-Crespo, Juan C

    2007-02-01

    Although the induction of mild to moderate cerebral hypothermia in mammals can have neuroprotective activity, some deleterious effects have been described when inducing deep hypothermia during cooling of the brain. In the spinal cord, rapid deep cooling can induce seizure activity accompanied by release of the excitatory neurotransmitters, glutamate and aspartate. We used cold-sensitive tropical amphibians as a model to determine (a) the critical temperature inside the central nervous system necessary to induce seizures during rapid cooling; (b) the survival rate during slow deep cooling of the whole animal; and (c) whether deep cooling can cause neuronal cell damage. Seizures induced by deep rapid (or=30 min) deep cooling of the whole animal (12 h at 2-3 degrees C), around 70% of animals died. Spinal reflexes were enhanced when temperatures within the spinal cord reached between 9.0 degrees C and 11.6 degrees C. A fivefold increase in blood glucose level was observed during slow deep cooling. Recovery after slow deep cooling was accompanied by motor impairment and the main histological findings were condensation of the cytoplasm and nuclear pyknosis. Severe neuronal cell damage was characterized by swelling, vacuolated cytoplasm with distended neuronal bodies. These results indicate that deep cooling can easily induce neuronal cell damage in the central nervous system of cold-sensitive animals. They also warn us to the potential sequels associated with the use of deep brain cooling as a neuroprotective strategy.

  6. Indirect hand and forearm vasomotion: Regional variations in cutaneous thermosensitivity during normothermia and mild hyperthermia.

    Science.gov (United States)

    Burdon, Catriona A; Tagami, Kyoko; Park, Joonhee; Caldwell, Joanne N; Taylor, Nigel A S

    2017-04-01

    In this experiment, hand and forearm vasomotor activity was investigated during localised, but stable heating and cooling of the face, hand and thigh, under open-loop (clamped) conditions. It was hypothesised that facial stimulation would provoke the most potent vascular changes. Nine individuals participated in two normothermic trials (mean body temperature clamp: 36.6°C; water-perfused suit and climate chamber) and two mildly hyperthermic trials (37.9°C). Localised heating (+5°C) and cooling (-5°C) stimuli were applied to equal surface areas of the face, hand and thigh (perfusion patches: 15min), while contralateral forearm or hand blood flows (venous-occlusion plethysmography) were measured (separate trials). Thermal sensation and discomfort votes were recorded before and during each thermal stimulation. When hyperthermic, local heating induced more sensitive vascular responses, with the combined thermosensitivity of both limb segments averaging 0.011mL·100mL -1 ·min -1 ·mmHg -1 ·°C -1 , and 0.005mL·100mL -1 ·min -1 ·mmHg -1 ·°C -1 during localised cooling (P0.05). Therefore, regional differences in vasomotor and sensory sensitivity appeared not to exist. When combined with previous observations of sudomotor sensitivity, it seems that, during mild heating and cooling, regional representations within the somatosensory cortex may not translate into meaningful differences in thermal sensation or the central integration of thermoafferent signals. It was concluded that inter-site variations in the cutaneous thermosensitivity of these thermolytic effectors have minimal physiological significance over the ranges investigated thus far. Copyright © 2017 Elsevier Ltd. All rights reserved.

  7. Method of hyperthermia and tumor size influence effectiveness of doxorubicin release from thermosensitive liposomes in experimental tumors.

    Science.gov (United States)

    Willerding, Linus; Limmer, Simone; Hossann, Martin; Zengerle, Anja; Wachholz, Kirsten; Ten Hagen, Timo L M; Koning, Gerben A; Sroka, Ronald; Lindner, Lars H; Peller, Michael

    2016-01-28

    Systemic chemotherapy of solid tumors could be enhanced by local hyperthermia (HT) in combination with thermosensitive liposomes (TSL) as drug carriers. In such an approach, effective HT of the tumor is considered essential for successful triggering local drug release and targeting of the drug to the tumor. To investigate the effect of HT method on the effectiveness of drug delivery, a novel laser-based HT device designed for the use in magnetic resonance imaging (MRI) was compared systematically with the frequently used cold light lamp and water bath HT. Long circulating phosphatidyldiglycerol-based TSL (DPPG2-TSL) with encapsulated doxorubicin (DOX) were used as drug carrier enabling intravascular drug release. Experiments were performed in male Brown Norway rats with a syngeneic soft tissue sarcoma (BN 175) located on both hind legs. One tumor was heated while the second tumor remained unheated as a reference. Six animals were investigated per HT method. DPPG2-TSL were injected i.v. at a stable tumor temperature above 40°C. Thereafter, temperature was maintained for 60min. Total DOX concentration in plasma, tumor tissue and muscle was determined post therapy by HPLC. Finally, the new laser-based device was tested in a MRI environment at 3T using DPPG2-TSL with encapsulated Gd-based contrast agent. All methods showed effective DOX delivery by TSL with 4.5-23.1ng/mg found in the heated tumors. In contrast, DOX concentration in the non-heated tumors was 0.5±0.1ng/mg. Independent of used HT methods, higher DOX levels were found in the smaller tumors. In comparison water bath induced lowest DOX delivery but still showing fourfold higher DOX concentrations compared to the non-heated tumors. With the laser-based applicator, a 13 fold higher DOX deposition was possible for large tumors and a 15 fold higher for the small tumors, respectively. Temperature gradients in the tumor tissue were higher with the laser and cold light lamp (-0.3°C/mm to -0.5°C/mm) compared to

  8. The preventive effect of resiniferatoxin on the development of cold hypersensitivity induced by spinal nerve ligation: involvement of TRPM8.

    Science.gov (United States)

    Koh, Won Uk; Choi, Seong-Soo; Kim, Ji Hyun; Yoon, Hye Joo; Ahn, Ho-Soo; Lee, Sun Kyung; Leem, Jeong Gil; Song, Jun Gol; Shin, Jin Woo

    2016-06-21

    Resiniferatoxin (RTX) is a potent analog of capsaicin and activates transient receptor potential (TRP) vanilloid type (TRPV) 1. In the current study, we investigated the preventive effect of perineural RTX on the development of cold hypersensitivity induced by spinal nerve ligation (SNL) in rats. Furthermore, we examined the association between the expression level of TRPV1, TRP ankyrin type (TRPA) 1 and TRP melastatin type (TRPM) 8 in the dorsal root ganglion (DRG) and cold hypersensitivity after SNL. RTX pretreatment prevented the development of SNL-induced hypersensitivity to mechanical, thermal, and cold stimuli. Western blot analysis 4 weeks after RTX pretreatment showed that RTX pretreatment decreased the protein expression level of SNL-induced TRPM8, but not TRPV1 or TRPA1, in the DRG of SNL rats. Immunofluorescent analysis revealed that up-regulated TRPM8-stained neurons after SNL co-localized with neurofilament 200-positive neurons located in the DRG. Pretreatment with perineural RTX significantly inhibits SNL-induced mechanical, thermal, and cold hypersensitivity. The antinociceptive effect of perineural RTX, especially on cold hypersensitivity, may be related to the suppression of TRPM8 expression in DRG.

  9. Junction temperature measurements via thermo-sensitive electrical parameters and their application to condition monitoring and active thermal control of power converters

    DEFF Research Database (Denmark)

    Baker, Nick; Liserre, Marco; Dupont, L.

    2013-01-01

    implementation of active thermal control to reduce losses and increase lifetime can be performed given an accurate knowledge of temperature. Temperature measurements via thermo-sensitive electrical parameters (TSEP) are one way to carry out immediate temperature readings on fully packaged devices. However...... scale implementation of these methods are discussed. Their potential use in the aforementioned goals in condition monitoring and active thermal control is also described....

  10. Establishment of an intermittent cold stress model using Tupaia belangeri and evaluation of compound C737 targeting neuron-restrictive silencer factor

    Science.gov (United States)

    Hai-Ying, Chi; Nagano, Kiori; Ezzikouri, Sayeh; Yamaguchi, Chiho; Kayesh, Mohammad Enamul Hoque; Rebbani, Khadija; Kitab, Bouchra; Nakano, Hirohumi; Kouji, Hiroyuki; Kohara, Michinori; Tsukiyama-Kohara, Kyoko

    2016-01-01

    Previous studies have shown that intermittent cold stress (ICS) induces depression-like behaviors in mammals. Tupaia belangeri (the tree shrew) is the only experimental animal other than the chimpanzee that has been shown to be susceptible to infection by hepatitis B and C viruses. Moreover, full genome sequence analysis has revealed strong homology between host proteins in Tupaia and in humans and other primates. Tupaia neuromodulator receptor proteins are also known to have a high degree of homology with their corresponding primate proteins. Based on these similarities, we hypothesized that induction of ICS in Tupaia would provide a useful animal model of stress responses. We exposed young adult Tupaia to ICS and observed decreases in body temperature and body weight in both female and male Tupaia, suggesting that Tupaia are an appropriate animal model for ICS studies. We further examined the efficacy of a new small-molecule compound, C737, against the effects of ICS. C737 mimics the helical structure of neuron-restrictive silencer factor (NRSF/REST), which regulates a wide range of target genes involved in neuronal function and pain modulation. Treatment with C737 significantly reduced stress-induced weight loss in female Tupaia; these effects were stronger than those elicited by the antidepressant agomelatine. These results suggest that Tupaia represents a useful non-rodent ICS model. Our data also provide new insights into the function of NRSF/REST in stress-induced depression and other disorders with epigenetic influences or those with high prevalence in women. PMID:27041457

  11. Ultrasound-mediated drug delivery using liposomes modified with a thermosensitive polymer.

    Science.gov (United States)

    Ninomiya, Kazuaki; Kawabata, Shinya; Tashita, Hiroyuki; Shimizu, Nobuaki

    2014-01-01

    Ultrasound-mediated drug delivery was established using liposomes that were modified with the thermosensitive polymer (TSP) poly(NIPMAM-co-NIPAM), which sensitized the liposomes to high temperatures. TSP-modified liposomes (TSP liposomes) released encapsulated calcein under 1 MHz ultrasound irradiation at 0.5 W/cm(2) for 120 s as well as the case under incubation at 42 °C for 15 min. In addition, uptake of the drug released from TSP liposomes by cancer cells was enhanced by ultrasound irradiation. In a cell injury assay using doxorubicin (DOX)-loaded TSP liposomes and ultrasound irradiation, cell viability of HepG2 cells at 6 h after ultrasound irradiation (1 MHz, 0.5 W/cm(2) for 30 s) with DOX-loaded TSP liposomes (TSP/lipid ratio=1) was 60%, which was significantly lower than that of the control conditions such as DOX-loaded TSP liposomes alone and DOX-loaded intact liposomes under ultrasound irradiation. Copyright © 2013 Elsevier B.V. All rights reserved.

  12. Novel transcriptional networks regulated by CLOCK in human neurons.

    Science.gov (United States)

    Fontenot, Miles R; Berto, Stefano; Liu, Yuxiang; Werthmann, Gordon; Douglas, Connor; Usui, Noriyoshi; Gleason, Kelly; Tamminga, Carol A; Takahashi, Joseph S; Konopka, Genevieve

    2017-11-01

    The molecular mechanisms underlying human brain evolution are not fully understood; however, previous work suggested that expression of the transcription factor CLOCK in the human cortex might be relevant to human cognition and disease. In this study, we investigated this novel transcriptional role for CLOCK in human neurons by performing chromatin immunoprecipitation sequencing for endogenous CLOCK in adult neocortices and RNA sequencing following CLOCK knockdown in differentiated human neurons in vitro. These data suggested that CLOCK regulates the expression of genes involved in neuronal migration, and a functional assay showed that CLOCK knockdown increased neuronal migratory distance. Furthermore, dysregulation of CLOCK disrupts coexpressed networks of genes implicated in neuropsychiatric disorders, and the expression of these networks is driven by hub genes with human-specific patterns of expression. These data support a role for CLOCK-regulated transcriptional cascades involved in human brain evolution and function. © 2017 Fontenot et al.; Published by Cold Spring Harbor Laboratory Press.

  13. A novel vehicle for local protein delivery to the inner ear: injectable and biodegradable thermosensitive hydrogel loaded with PLGA nanoparticles.

    Science.gov (United States)

    Dai, Juan; Long, Wei; Liang, Zhongping; Wen, Lu; Yang, Fan; Chen, Gang

    2018-01-01

    Delivery of biomacromolecular drugs into the inner ear is challenging, mainly because of their inherent instability as well as physiological and anatomical barriers. Therefore, protein-friendly, hydrogel-based delivery systems following local administration are being developed for inner ear therapy. Herein, biodegradable poly(lactic-co-glycolic acid) (PLGA) nanoparticles (NPs) containing interferon α-2 b (IFN α-2 b) were loaded in chitosan/glycerophosphate (CS/GP)-based thermosensitive hydrogel for IFN delivery by intratympanic injection. The injectable hydrogel possessed a physiological pH and formed semi-solid gel at 37 °C, with good swelling and deswelling properties. The CS/GP hydrogel could slowly degrade as visualized by scanning electron microscopy (SEM). The presence of NPs in CS/GP gel largely influenced in vitro drug release. In the guinea pig cochlea, a 1.5- to 3-fold increase in the drug exposure time of NPs-CS/GP was found than those of the solution, NPs and IFN-loaded hydrogel. Most importantly, a prolonged residence time was attained without obvious histological changes in the inner ear. This biodegradable, injectable, and thermosensitive NPs-CS/GP system may allow longer delivery of protein drugs to the inner ear, thus may be a potential novel vehicle for inner ear therapy.

  14. Ciguatoxins activate specific cold pain pathways to elicit burning pain from cooling.

    Science.gov (United States)

    Vetter, Irina; Touska, Filip; Hess, Andreas; Hinsbey, Rachel; Sattler, Simon; Lampert, Angelika; Sergejeva, Marina; Sharov, Anastasia; Collins, Lindon S; Eberhardt, Mirjam; Engel, Matthias; Cabot, Peter J; Wood, John N; Vlachová, Viktorie; Reeh, Peter W; Lewis, Richard J; Zimmermann, Katharina

    2012-10-03

    Ciguatoxins are sodium channel activator toxins that cause ciguatera, the most common form of ichthyosarcotoxism, which presents with peripheral sensory disturbances, including the pathognomonic symptom of cold allodynia which is characterized by intense stabbing and burning pain in response to mild cooling. We show that intraplantar injection of P-CTX-1 elicits cold allodynia in mice by targeting specific unmyelinated and myelinated primary sensory neurons. These include both tetrodotoxin-resistant, TRPA1-expressing peptidergic C-fibres and tetrodotoxin-sensitive A-fibres. P-CTX-1 does not directly open heterologously expressed TRPA1, but when co-expressed with Na(v) channels, sodium channel activation by P-CTX-1 is sufficient to drive TRPA1-dependent calcium influx that is responsible for the development of cold allodynia, as evidenced by a large reduction of excitatory effect of P-CTX-1 on TRPA1-deficient nociceptive C-fibres and of ciguatoxin-induced cold allodynia in TRPA1-null mutant mice. Functional MRI studies revealed that ciguatoxin-induced cold allodynia enhanced the BOLD (Blood Oxygenation Level Dependent) signal, an effect that was blunted in TRPA1-deficient mice, confirming an important role for TRPA1 in the pathogenesis of cold allodynia.

  15. Bilateral Neuropathy of Primary Sensory Neurons by the Chronic Compression of Multiple Unilateral DRGs

    Directory of Open Access Journals (Sweden)

    Ya-Bin Xie

    2016-01-01

    Full Text Available To mimic multilevel nerve root compression and intervertebral foramina stenosis in human, we established a new animal model of the chronic compression of unilateral multiple lumbar DRGs (mCCD in the rat. A higher occurrence of signs of spontaneous pain behaviors, such as wet-dog shaking and spontaneous hind paw shrinking behaviors, was firstly observed from day 1 onward. In the meantime, the unilateral mCCD rat exhibited significant bilateral hind paw mechanical and cold allodynia and hyperalgesia, as well as a thermal preference to 30°C plate between 30 and 35°C. The expression of activating transcription factor 3 (ATF3 was significantly increased in the ipsilateral and contralateral all-sized DRG neurons after the mCCD. And the expression of CGRP was significantly increased in the ipsilateral and contralateral large- and medium-sized DRG neurons. ATF3 and CGRP expressions correlated to evoked pain hypersensitivities such as mechanical and cold allodynia on postoperative day 1. The results suggested that bilateral neuropathy of primary sensory neurons might contribute to bilateral hypersensitivity in the mCCD rat.

  16. An acute injection of corticosterone increases thyrotrophin-releasing hormone expression in the paraventricular nucleus of the hypothalamus but interferes with the rapid hypothalamus pituitary thyroid axis response to cold in male rats.

    Science.gov (United States)

    Sotelo-Rivera, I; Jaimes-Hoy, L; Cote-Vélez, A; Espinoza-Ayala, C; Charli, J-L; Joseph-Bravo, P

    2014-12-01

    The activity of the hypothalamic-pituitary-thyroid (HPT) axis is rapidly adjusted by energy balance alterations. Glucocorticoids can interfere with this activity, although the timing of this interaction is unknown. In vitro studies indicate that, albeit incubation with either glucocorticoid receptor (GR) agonists or protein kinase A (PKA) activators enhances pro-thyrotrophin-releasing hormone (pro-TRH) transcription, co-incubation with both stimuli reduces this enhancement. In the present study, we used primary cultures of hypothalamic cells to test whether the order of these stimuli alters the cross-talk. We observed that a simultaneous or 1-h prior (but not later) activation of GR is necessary to inhibit the stimulatory effect of PKA activation on pro-TRH expression. We tested these in vitro results in the context of a physiological stimulus on the HPT axis in adult male rats. Cold exposure for 1 h enhanced pro-TRH mRNA expression in neurones of the hypophysiotrophic and rostral subdivisions of the paraventricular nucleus (PVN) of the hypothalamus, thyrotrophin (TSH) serum levels and deiodinase 2 (D2) activity in brown adipose tissue (BAT). An i.p. injection of corticosterone stimulated pro-TRH expression in the PVN of rats kept at ambient temperature, more pronouncedly in hypophysiotrophic neurones that no longer responded to cold exposure. In corticosterone-pretreated rats, the cold-induced increase in pro-TRH expression was detected only in the rostral PVN. Corticosterone blunted the increase in serum TSH levels and D2 activity in BAT produced by cold in vehicle-injected animals. Thus, increased serum corticosterone levels rapidly restrain cold stress-induced activation of TRH hypophysiotrophic neurones, which may contribute to changing energy expenditure. Interestingly, TRH neurones of the rostral PVN responded to both corticosterone and cold exposure with an amplified expression of pro-TRH mRNA, suggesting that these neurones integrate stress and temperature

  17. Dopaminergic neurons encode a distributed, asymmetric representation of temperature in Drosophila.

    Science.gov (United States)

    Tomchik, Seth M

    2013-01-30

    Dopaminergic circuits modulate a wide variety of innate and learned behaviors in animals, including olfactory associative learning, arousal, and temperature-preference behavior. It is not known whether distinct or overlapping sets of dopaminergic neurons modulate these behaviors. Here, I have functionally characterized the dopaminergic circuits innervating the Drosophila mushroom body with in vivo calcium imaging and conditional silencing of genetically defined subsets of neurons. Distinct subsets of PPL1 dopaminergic neurons innervating the vertical lobes of the mushroom body responded to decreases in temperature, but not increases, with rapidly adapting bursts of activity. PAM neurons innervating the horizontal lobes did not respond to temperature shifts. Ablation of the antennae and maxillary palps reduced, but did not eliminate, the responses. Genetic silencing of dopaminergic neurons innervating the vertical mushroom body lobes substantially reduced behavioral cold avoidance, but silencing smaller subsets of these neurons had no effect. These data demonstrate that overlapping dopaminergic circuits encode a broadly distributed, asymmetric representation of temperature that overlays regions implicated previously in learning, memory, and forgetting. Thus, diverse behaviors engage overlapping sets of dopaminergic neurons that encode multimodal stimuli and innervate a single anatomical target, the mushroom body.

  18. Warm hands, cold heart: progressive whole-body cooling increases warm thermosensitivity of human hands and feet in a dose-dependent fashion.

    Science.gov (United States)

    Filingeri, Davide; Morris, Nathan B; Jay, Ollie

    2017-01-01

    What is the central question of this study? Investigations on inhibitory/facilitatory modulation of vision, touch and pain show that conditioning stimuli outside the receptive field of testing stimuli modulate the central processing of visual, touch and painful stimuli. We asked whether contextual modulation also exists in human temperature integration. What is the main finding and its importance? Progressive decreases in whole-body mean skin temperature (the conditioning stimulus) significantly increased local thermosensitivity to skin warming but not cooling (the testing stimuli) in a dose-dependent fashion. In resembling the central mechanisms underlying endogenous analgesia, our findings point to the existence of an endogenous thermosensory system in humans that could modulate local skin thermal sensitivity to facilitate thermal behaviour. Although inhibitory/facilitatory central modulation of vision and pain has been investigated, contextual modulation of skin temperature integration has not been explored. Hence, we tested whether progressive decreases in whole-body mean skin temperature (T sk ; a large conditioning stimulus) alter the magnitude estimation of local warming and cooling stimuli applied to hairy and glabrous skin. On four separate occasions, eight men (27 ± 5 years old) underwent a 30 min whole-body cooling protocol (water-perfused suit; temperature, 5°C), during which a quantitative thermosensory test, consisting of reporting the perceived magnitude of warming and cooling stimuli (±8°C from 30°C baseline) applied to the hand (palm/dorsum) and foot (sole/dorsum), was performed before cooling and every 10 min thereafter. The cooling protocol resulted in large progressive reductions in T sk [10 min, -3.36°C (95% confidence interval -2.62 to -4.10); 20 min, -5.21°C (-4.47 to -5.95); and 30 min, -6.32°C (-5.58 to -7.05); P fashion. In highlighting a novel feature of human temperature integration, these findings point to the existence

  19. Cutaneous TRPM8-expressing sensory afferents are a small population of neurons with unique firing properties.

    Science.gov (United States)

    Jankowski, Michael P; Rau, Kristofer K; Koerber, H Richard

    2017-04-01

    It has been well documented that the transient receptor potential melastatin 8 (TRPM8) receptor is involved in environmental cold detection. The role that this receptor plays in nociception however, has been somewhat controversial since conflicting reports have shown different neurochemical identities and responsiveness of TRPM8 neurons. In order to functionally characterize cutaneous TRMP8 fibers, we used two ex vivo somatosensory recording preparations to functionally characterize TRPM8 neurons that innervate the hairy skin in mice genetically engineered to express GFP from the TRPM8 locus. We found several types of cold-sensitive neurons that innervate the hairy skin of the mouse but the TRPM8-expressing neurons were found to be of two specific populations that responded with rapid firing to cool temperatures. The first group was mechanically insensitive but the other did respond to high threshold mechanical deformation of the skin. None of these fibers were found to contain calcitonin gene-related peptide, transient receptor potential vanilloid type 1 or bind isolectin B4. These results taken together with other reports suggest that TRPM8 containing sensory neurons are environmental cooling detectors that may be nociceptive or non-nociceptive depending on the sensitivity of individual fibers to different combinations of stimulus modalities. © 2017 The Authors. Physiological Reports published by Wiley Periodicals, Inc. on behalf of The Physiological Society and the American Physiological Society.

  20. Radiation synthesis and characterization of thermo-sensitive PNIPA/clay hydrogels

    International Nuclear Information System (INIS)

    Song Hongyan; He Suqin; Liu Wentao; Zhu Chengshen; Yang Mingcheng

    2007-01-01

    In this work, the thermo-sensitive hydrogels of PNIPA/Clay were synthesized by 60 Co-γ rays irradiation. The effects of organically modified clay and Na + clay, clay content, and dispersing condition on swelling behavior of PNIPA/clay hydrogels were investigated. The results showed that the equilibrium swelling ratio (SR) of the PNIPA/clay hydrogels is better than PNIPA, and the SR of PNIPA/organically modified clay hydrogels is the highest. With clay content increases, the SR of hydrogels became better. The deswelling behavior of hydrogel was improved, the deswelling ratio of the hydrogel with organically modified clay is highest, and ratio of losing water is 83%, while PNIPA is about 50%. The compressive properties of hydrogel composites were also examined. The results showed that the compressive properties of the PNIPA/clay hydrogels were improved distinctly than that of the conventional hydrogels without clay. And with increasing of clay content, the compressive properties of hydrogel composites improve rapidly. When the content of clay is 15%, the maximum compression force of the PNIPA/clay hydrogel is 5.28N, which is 14 times of PNIPA hydrogel and compression strength is 2.5 times. (authors)

  1. Detection of cold pain, cold allodynia and cold hyperalgesia in freely behaving rats

    Directory of Open Access Journals (Sweden)

    Woolf Clifford J

    2005-12-01

    Full Text Available Abstract Background Pain is elicited by cold, and a major feature of many neuropathic pain states is that normally innocuous cool stimuli begin to produce pain (cold allodynia. To expand our understanding of cold induced pain states we have studied cold pain behaviors over a range of temperatures in several animal models of chronic pain. Results We demonstrate that a Peltier-cooled cold plate with ± 1°C sensitivity enables quantitative measurement of a detection withdrawal response to cold stimuli in unrestrained rats. In naïve rats the threshold for eliciting cold pain behavior is 5°C. The withdrawal threshold for cold allodynia is 15°C in both the spared nerve injury and spinal nerve ligation models of neuropathic pain. Cold hyperalgesia is present in the spared nerve injury model animals, manifesting as a reduced latency of withdrawal response threshold at temperatures that elicit cold pain in naïve rats. We also show that following the peripheral inflammation produced by intraplantar injection of complete Freund's adjuvant, a hypersensitivity to cold occurs. Conclusion The peltier-cooled provides an effective means of assaying cold sensitivity in unrestrained rats. Behavioral testing of cold allodynia, hyperalgesia and pain will greatly facilitate the study of the neurobiological mechanisms involved in cold/cool sensations and enable measurement of the efficacy of pharmacological treatments to reduce these symptoms.

  2. Thermal effects of whole head submersion in cold water on nonshivering humans.

    Science.gov (United States)

    Pretorius, Thea; Bristow, Gerald K; Steinman, Alan M; Giesbrecht, Gordon G

    2006-08-01

    This study isolated the effect of whole head submersion in cold water, on surface heat loss and body core cooling, when the confounding effect of shivering heat production was pharmacologically eliminated. Eight healthy male subjects were studied in 17 degrees C water under four conditions: the body was either insulated or uninsulated, with the head either above the water or completely submersed in each body-insulation subcondition. Shivering was abolished with buspirone (30 mg) and meperidine (2.5 mg/kg), and subjects breathed compressed air throughout all trials. Over the first 30 min of immersion, exposure of the head increased core cooling both in the body-insulated conditions (head out: 0.47 +/- 0.2 degrees C, head in: 0.77 +/- 0.2 degrees C; P body-exposed conditions (head out: 0.84 +/- 0.2 degrees C and head in: 1.17 +/- 0.5 degrees C; P body surface area) in the body-exposed conditions increased total heat loss by only 10%. In both body-exposed and body-insulated conditions, head submersion increased core cooling rate much more (average of 42%) than it increased total heat loss. This may be explained by a redistribution of blood flow in response to stimulation of thermosensitive and/or trigeminal receptors in the scalp, neck and face, where a given amount of heat loss would have a greater cooling effect on a smaller perfused body mass. In 17 degrees C water, the head does not contribute relatively more than the rest of the body to surface heat loss; however, a cold-induced reduction of perfused body mass may allow this small increase in heat loss to cause a relatively larger cooling of the body core.

  3. Amino-functionalized poloxamer 407 with both mucoadhesive and thermosensitive properties: preparation, characterization and application in a vaginal drug delivery system

    Directory of Open Access Journals (Sweden)

    Liqian Ci

    2017-09-01

    Full Text Available Lack of mucoadhesive properties is the major drawback to poloxamer 407 (F127-based in situ hydrogels for mucosal administration. The objective of the present study was to construct a novel mucoadhesive and thermosensitive in situ hydrogel drug delivery system based on an amino-functionalized poloxamer for vaginal administration. First, amino-functionalized poloxamer 407 (F127-NH2 was synthesized and characterized with respect to its micellization behavior and interaction with mucin. Then using acetate gossypol (AG as model drug, AG-loaded F127-NH2-based in situ hydrogels (NFGs were evaluated with respect to rheology, drug release, ex vivo vaginal mucosal adhesion, in vivo intravaginal retention and local irritation after vaginal administration to healthy female mice. The results show that F127-NH2 is capable of forming a thermosensitive in situ hydrogel with sustained drug release properties. An interaction between positively charged F127-NH2 and negatively charged mucin was revealed by changes in the particle size and zeta potential of mucin particles as well as an increase in the complex modulus of NFG caused by mucin. Ex vivo and in vivo fluorescence imaging and quantitative analysis of the amount of AG remaining in mouse vaginal lavage all demonstrated greater intravaginal retention of NFG than that of an unmodified F127-based in situ hydrogel. In conclusion, amino group functionalization confers valuable mucoadhesive properties on poloxamer 407.

  4. Neurons other than motor neurons in motor neuron disease.

    Science.gov (United States)

    Ruffoli, Riccardo; Biagioni, Francesca; Busceti, Carla L; Gaglione, Anderson; Ryskalin, Larisa; Gambardella, Stefano; Frati, Alessandro; Fornai, Francesco

    2017-11-01

    Amyotrophic lateral sclerosis (ALS) is typically defined by a loss of motor neurons in the central nervous system. Accordingly, morphological analysis for decades considered motor neurons (in the cortex, brainstem and spinal cord) as the neuronal population selectively involved in ALS. Similarly, this was considered the pathological marker to score disease severity ex vivo both in patients and experimental models. However, the concept of non-autonomous motor neuron death was used recently to indicate the need for additional cell types to produce motor neuron death in ALS. This means that motor neuron loss occurs only when they are connected with other cell types. This concept originally emphasized the need for resident glia as well as non-resident inflammatory cells. Nowadays, the additional role of neurons other than motor neurons emerged in the scenario to induce non-autonomous motor neuron death. In fact, in ALS neurons diverse from motor neurons are involved. These cells play multiple roles in ALS: (i) they participate in the chain of events to produce motor neuron loss; (ii) they may even degenerate more than and before motor neurons. In the present manuscript evidence about multi-neuronal involvement in ALS patients and experimental models is discussed. Specific sub-classes of neurons in the whole spinal cord are reported either to degenerate or to trigger neuronal degeneration, thus portraying ALS as a whole spinal cord disorder rather than a disease affecting motor neurons solely. This is associated with a novel concept in motor neuron disease which recruits abnormal mechanisms of cell to cell communication.

  5. Novel dual-reverse thermosensitive solid lipid nanoparticle-loaded hydrogel for rectal administration of flurbiprofen with improved bioavailability and reduced initial burst effect.

    Science.gov (United States)

    Din, Fakhar Ud; Mustapha, Omer; Kim, Dong Wuk; Rashid, Rehmana; Park, Jong Hyuck; Choi, Ju Yeon; Ku, Sae Kwang; Yong, Chul Soon; Kim, Jong Oh; Choi, Han-Gon

    2015-08-01

    The purpose of this study was to develop novel solid lipid nanoparticle (SLN)-loaded dual-reverse thermosensitive hydrogel (DRTH) for rectal administration of flurbiprofen with improved bioavailability and reduced initial burst effect. The flurbiprofen-loaded SLNs were prepared by hot homogenisation technique, after optimising the amounts of lipid mixture (tricaprin and triethanolamine in 8:2 weight ratio), drug and surfactant. The flurbiprofen-loaded thermosensitive SLN composed of drug, lipid mixture and surfactant at a weight ratio of 10/15/1.3 was a solid at room temperature, and changed to liquid form at physiological temperature due to its melting point of about 32°C. This SLN gave the mean particle size of about 190nm and entrapment efficiency of around 90%. The DRTHs were prepared by adding this flurbiprofen-loaded thermosensitive SLN in various poloxamer solutions. Their rheological characterisation, release and stability were investigated while a morphological and pharmacokinetic study was performed after its rectal administration to rats compared with the drug and hydrogel. Poloxamer 188 and SLN decreased the gelation temperature and gelation time, but increased the viscosity at 25°C, gel strength and mucoadhesive force of DRTHs. In particular, the DRTH composed of [SLN/P 407/P 188 (10%/15%/25%)] with the gelation temperature of about 35°C existed as liquid at room temperature, but gelled at 30-36°C, leading to opposite reversible property of SLN. Thus, it was easy to administer rectally, and it gelled rapidly inside the body. This DRTH gave a significantly increased dissolution rate of the drug as compared to the flurbiprofen, but significantly retarded as compared to the hydrogel, including the initial dissolution rate. Moreover, this DRTH gave significantly higher plasma concentration and 7.5-fold AUC values compared to the drug, and lower initial plasma concentration and Cmax value compared to the hydrogel due to reduced initial burst effect. No

  6. Synthesis and characterization of injectable, thermosensitive, and biocompatible acellular bone matrix/poly(ethylene glycol)-poly (ε-caprolactone)-poly(ethylene glycol) hydrogel composite.

    Science.gov (United States)

    Ni, Pei-Yan; Fan, Min; Qian, Zhi-Yong; Luo, Jing-Cong; Gong, Chang-Yang; Fu, Shao-Zhi; Shi, Shuai; Luo, Feng; Yang, Zhi-Ming

    2012-01-01

    In orthopedic tissue engineering, the extensively applied acellular bone matrix (ABM) can seldom be prefabricated just right to mold the cavity of the diverse defects, might induce severe inflammation on account of the migration of small granules and usually bring the patients great pain in the treatment. In this study, a new injectable thermosensitive ABM/PECE composite with good biocompatibility was designed and prepared by adding the ABM granules into the triblock copolymer poly(ethylene eglycol)-poly(ε-caprolactone)-poly(ethylene eglycol) (PEG-PCL-PEG, PECE). The PECE was synthesized by ring-opening copolymerization and characterized by ¹H NMR. The ABM was prepared by acellular treatment of natural bone and ground to fine granules. The obtained ABM/PECE composite showed the most important absorption bands of ABM and PECE copolymer in FT-IR spectroscopy and underwent sol-gel phage transition from solution to nonflowing hydrogel at 37°C. SEM results indicated that the ABM/PECE composite with different ABM contents all presented similar porous 3D structure. ABM/PECE composite presented mild cytotoxicity to rat MSCs in vitro and good biocompatibility in the BALB/c mice subcutis up to 4 weeks. In conclusion, all the results confirmed that the injectable thermosensitive ABM/PECE composite was a promising candidate for orthopedic tissue engineering in a minimally-invasive way. Copyright © 2011 Wiley Periodicals, Inc.

  7. How cold is cold dark matter?

    International Nuclear Information System (INIS)

    Armendariz-Picon, Cristian; Neelakanta, Jayanth T.

    2014-01-01

    If cold dark matter consists of particles, these must be non-interacting and non-relativistic by definition. In most cold dark matter models however, dark matter particles inherit a non-vanishing velocity dispersion from interactions in the early universe, a velocity that redshifts with cosmic expansion but certainly remains non-zero. In this article, we place model-independent constraints on the dark matter temperature to mass ratio, whose square root determines the dark matter velocity dispersion. We only assume that dark matter particles decoupled kinetically while non-relativistic, when galactic scales had not entered the horizon yet, and that their momentum distribution has been Maxwellian since that time. Under these assumptions, using cosmic microwave background and matter power spectrum observations, we place upper limits on the temperature to mass ratio of cold dark matter today (away from collapsed structures). These limits imply that the present cold dark matter velocity dispersion has to be smaller than 54 m/s. Cold dark matter has to be quite cold, indeed

  8. Cold Antimatter Plasmas, and Aspirations for Cold Antihydrogen

    Science.gov (United States)

    2002-06-24

    UNCLASSIFIED Defense Technical Information Center Compilation Part Notice ADP012494 TITLE: Cold Antimatter Plasmas, and Aspirations for Cold...part numbers comprise the compilation report: ADP012489 thru ADP012577 UNCLASSIFIED Cold Antimatter Plasmas, and Aspirations for Cold Antihydrogen G...and positrons. The antiprotons come initially from the new Antiproton Decel- erator facility at CERN. Good control of such cold antimatter plasmas is

  9. Novel role of cold/menthol-sensitive transient receptor potential melastatine family member 8 (TRPM8) in the activation of store-operated channels in LNCaP human prostate cancer epithelial cells.

    NARCIS (Netherlands)

    Thebault, S.C.; Lemonnier, L.; Bidaux, G.; Flourakis, M.; Bavencoffe, A.; Gordienko, D.; Roudbaraki, M.; Delcourt, P.; Panchin, Y.; Shuba, Y.; Skryma, R.; Prevarskaya, N.

    2005-01-01

    Recent cloning of a cold/menthol-sensitive TRPM8 channel (transient receptor potential melastatine family member 8) from rodent sensory neurons has provided the molecular basis for the cold sensation. Surprisingly, the human orthologue of rodent TRPM8 also appears to be strongly expressed in the

  10. Different requirements of functional telomeres in neural stem cells and terminally differentiated neurons.

    Science.gov (United States)

    Lobanova, Anastasia; She, Robert; Pieraut, Simon; Clapp, Charlie; Maximov, Anton; Denchi, Eros Lazzerini

    2017-04-01

    Telomeres have been studied extensively in peripheral tissues, but their relevance in the nervous system remains poorly understood. Here, we examine the roles of telomeres at distinct stages of murine brain development by using lineage-specific genetic ablation of TRF2, an essential component of the shelterin complex that protects chromosome ends from the DNA damage response machinery. We found that functional telomeres are required for embryonic and adult neurogenesis, but their uncapping has surprisingly no detectable consequences on terminally differentiated neurons. Conditional knockout of TRF2 in post-mitotic immature neurons had virtually no detectable effect on circuit assembly, neuronal gene expression, and the behavior of adult animals despite triggering massive end-to-end chromosome fusions across the brain. These results suggest that telomeres are dispensable in terminally differentiated neurons and provide mechanistic insight into cognitive abnormalities associated with aberrant telomere length in humans. © 2017 Lobanova et al.; Published by Cold Spring Harbor Laboratory Press.

  11. Hypothermic general cold adaptation induced by local cold acclimation.

    Science.gov (United States)

    Savourey, G; Barnavol, B; Caravel, J P; Feuerstein, C; Bittel, J H

    1996-01-01

    To study relationships between local cold adaptation of the lower limbs and general cold adaptation, eight subjects were submitted both to a cold foot test (CFT, 5 degrees C water immersion, 5 min) and to a whole-body standard cold air test (SCAT, 1 degree C, 2 h, nude at rest) before and after a local cold acclimation (LCA) of the lower limbs effected by repeated cold water immersions. The LCA induced a local cold adaptation confirmed by higher skin temperatures of the lower limbs during CFT and a hypothermic insulative general cold adaptation (decreased rectal temperature and mean skin temperature P adaptation was related to the habituation process confirmed by decreased plasma concentrations of noradrenaline (NA) during LCA (P general cold adaptation was unrelated either to local cold adaptation or to the habituation process, because an increased NA during SCAT after LCA (P syndrome" occurring during LCA.

  12. Cold Stress

    Science.gov (United States)

    ... Publications and Products Programs Contact NIOSH NIOSH COLD STRESS Recommend on Facebook Tweet Share Compartir Workers who ... cold environments may be at risk of cold stress. Extreme cold weather is a dangerous situation that ...

  13. Effects of endogenous pyrogen and prostaglandin E2 on hypothalamic neurons in rat brain slices.

    Science.gov (United States)

    Watanabe, T; Morimoto, A; Murakami, N

    1987-06-01

    We investigated the effects of endogenous pyrogen and prostaglandin E2 (PGE2) on the preoptic and anterior hypothalamic (POAH) neurons using brain slice preparations from the rat. Partially purified endogenous pyrogen did not change the activities of most of the neurons in the POAH region when applied locally through a micropipette attached to the recording electrode in proximity to the neurons. This indicates that partially purified endogenous pyrogen does not act directly on the neuronal activity in the POAH region. The partially purified endogenous pyrogen, applied into a culture chamber containing a brain slice, facilitated the activities in 24% of the total neurons tested, regardless of the thermal specificity of the neurons. Moreover, PGE2 added to the culture chamber facilitated 48% of the warm-responsive, 33% of the cold-responsive, and 29% of the thermally insensitive neurons. The direction of change in neuronal activity induced by partially purified endogenous pyrogen appears to be almost the same as that induced by PGE2 when these substances were applied by perfusion to the same neuron in the culture chamber. These results suggest that partially purified pyrogen applied to the perfusate of the culture chamber stimulates some constituents of brain tissue to synthesize and release prostaglandin, which in turn affects the neuronal activity of the POAH region.

  14. TRP channel blamed for burning cold after a tropical fish meal

    Science.gov (United States)

    Voets, Thomas

    2012-01-01

    EMBO J (2012) 31 19, 3795–3808 doi:10.1038/emboj.2012.207; published online 07312012 Ciguatera is one of the most common forms of food poisoning, occurring after consumption of fish contaminated with ciguatoxins. New work by Vetter et al (2012) reveals the key molecular players that underlie the altered temperature sensation associated with ciguatera. In particular, they show that ciguatoxins act on sensory neurons that express TRPA1, an ion channel implicated in the detection of noxious cold. PMID:22960637

  15. The role of trigeminal nasal TRPM8-expressing afferent neurons in the antitussive effects of menthol.

    Science.gov (United States)

    Plevkova, J; Kollarik, M; Poliacek, I; Brozmanova, M; Surdenikova, L; Tatar, M; Mori, N; Canning, B J

    2013-07-15

    The cold-sensitive cation channel TRPM8 is a target for menthol, which is used routinely as a cough suppressant and as an additive to tobacco and food products. Given that cold temperatures and menthol activate neurons through gating of TRPM8, it is unclear how menthol actively suppresses cough. In this study we describe the antitussive effects of (-)-menthol in conscious and anesthetized guinea pigs. In anesthetized guinea pigs, cough evoked by citric acid applied topically to the tracheal mucosa was suppressed by menthol only when it was selectively administered as vapors to the upper airways. Menthol applied topically to the tracheal mucosa prior to and during citric acid application or administered continuously as vapors or as an aerosol to the lower airways was without effect on cough. These actions of upper airway menthol treatment were mimicked by cold air delivered to the upper airways but not by (+)-menthol, the inactive isomer of menthol, or by the TRPM8/TRPA1 agonist icilin administered directly to the trachea. Subsequent molecular analyses confirmed the expression of TRPM8 in a subset of nasal trigeminal afferent neurons that do not coincidently express TRPA1 or TRPV1. We conclude that menthol suppresses cough evoked in the lower airways primarily through a reflex initiated from the nose.

  16. Poly (N-isopropylacrylamide)-functionalized dendrimer as a thermosensitive nanoplatform for delivering malloapelta B against HepG2 cancer cell proliferation

    Science.gov (United States)

    Ngan Le, Phung; Chuong Pham, Dinh; Hai Nguyen, Dai; Quyen Tran, Ngoc; Dimitrov, Vladimir; Ivanov, Petko; Nguyen Xuan, Cuong; Nguyen, Hoai Nam; Khoa Nguyen, Cuu

    2017-06-01

    In recent years, nanocarriers have emerged as effective platforms for delivering several kinds of herbal medicine and naturally bioactive compounds. In this study we developed an outstanding thermosensitive dendritic nanocarrier to efficiently deliver malloapelta B (Mall B), which is a water insoluble bioactive compound isolated from leaves of Mallotus apelta—Vietnamese medicinal plant. The thermosensitive poly(N-isopropylacrylamide) (PNIPAM) polymer-conjugated polyamidoamine (PAMAM) dendrimer copolymer was prepared via Michael reaction. The copolymer structures were confirmed by proton nuclear magnectic resonance (1H NMR). Morphology of the nanocarrier was observered around 70-120 nm by transmission electron microscopy (TEM). Size distributions were measured by dynamic light scattering (DLS) of the nanocarrier and its Mall B-loaded performed at 146.8 nm and 194.5 nm, respectively. The PNIPAM-g-PAMAM-based nanocarrier exhibited higher Mall B loading efficiency (DL  =  59.93  ±  0.19%) and entrapment efficiency (EE  =  89.98  ±  2.06%) as compared to PNIPAM (DL  =  52.54  ±  0.45% and EE  =  66.45  ±  2.78%). In vitro release indicated that approximately 30% amount of the loaded Mall B released at pH 5.5 after 54 h tracking. At the same time, 12.5% amount of the molecules released at pH 7.4.Cytotoxicity assay results showed that the Mall B-loaded nanocarrier significantly inhibited HepG2 cancer cell proliferation. These obtained results indicated that the nanocarrier could solve hydrophobic property of Mall B for further medicine applications.

  17. In vitro-in vivo evaluation of in situ gelling and thermosensitive ketoprofen liquid suppositories.

    Science.gov (United States)

    Ozgüney, Işık; Kardhiqi, Anita; Yıldız, Gülbeyaz; Ertan, Gökhan

    2014-12-01

    The main objective of this study was to investigate the release and pharmacokinetic profiles of ketoprofen (KP) from developed thermosensitive and mucoadhesive liquid suppositories. Thermosensitive liquid suppositories were prepared using KP, poloxamer 407 (P 407), poloxamer 188 (P 188) and various amounts of different mucoadhesive polymers. In vitro release studies was monitored by the USP XXVI paddle method. The results thus obtained were evaluated kinetically and mechanism of release was analyzed. Identification of poloxamer gel localization in vivo was conducted using white male rabbits by adding 1 % methylene blue. For in vivo studies, twenty-four white male rabbits were randomly divided into three groups. The rabbits in each group were administered with liquid suppository F1 [P407/P188/KP (4/20/2.5 %)], F5 [P407/P188/KP/C (4/20/2.5/0.8 %)] or conventional suppository (F-C) into the rectum. The plasma concentration of KP was analyzed by high performance liquid chromatography (HPLC). C max, AUC, MRT and T max were evaluated. The release of KP was variously affected by the mucoadhesive polymers. In vitro release studies showed that Carbopol 934 P(C) has significant effect on release rate among the mucoadhesive polymers. When the formulations were evaluated kinetically, different kinetic models were obtained. Formulation F6 [P407/P188/KP/C (4/20/2.5/1.6 %)] which contains the highest C concentration and very high viscosity, shows a significantly better fit with Higuchi kinetic model. n value of this formulation was also found approximately 0.5. n exponent results of the other formulations showed that KP might be released from the suppositories by non-Fickian diffusion. Identification of poloxamer gel localization in vivo showed that the suppositories remain in the rectum without leakage after administration. With regard to the results of in vivo studies, the AUC6→14 values of KP in liquid suppository containing C are significantly higher than those in

  18. Thermo-sensitive liposomes loaded with doxorubicin and lysine modified single-walled carbon nanotubes as tumor-targeting drug delivery system.

    Science.gov (United States)

    Zhu, Xiali; Xie, Yingxia; Zhang, Yingjie; Huang, Heqing; Huang, Shengnan; Hou, Lin; Zhang, Huijuan; Li, Zhi; Shi, Jinjin; Zhang, Zhenzhong

    2014-11-01

    This report focuses on the thermo-sensitive liposomes loaded with doxorubicin and lysine-modified single-walled carbon nanotube drug delivery system, which was designed to enhance the anti-tumor effect and reduce the side effects of doxorubicin. Doxorubicin-lysine/single-walled carbon nanotube-thermo-sensitive liposomes was prepared by reverse-phase evaporation method, the mean particle size was 232.0 ± 5.6 nm, and drug entrapment efficiency was 86.5 ± 3.7%. The drug release test showed that doxorubicin released more quickly at 42℃ than at 37℃. Compared with free doxorubicin, doxorubicin-lysine/single-walled carbon nanotube-thermo-sensitive liposomes could efficiently cross the cell membranes and afford higher anti-tumor efficacy on the human hepatic carcinoma cell line (SMMC-7721) cells in vitro. For in vivo experiments, the relative tumor volumes of the sarcomaia 180-bearing mice in thermo-sensitive liposomes group and doxorubicin group were significantly smaller than those of N.S. group. Meanwhile, the combination of near-infrared laser irradiation at 808 nm significantly enhanced the tumor growth inhibition both on SMMC-7721 cells and the sarcomaia 180-bearing mice. The quality of life such as body weight, mental state, food and water intake of sarcomaia 180 tumor-bearing mice treated with doxorubicin-lysine/single-walled carbon nanotube-thermo-sensitive liposomes were much higher than those treated with doxorubicin. In conclusion, doxorubicin-lysine/single-walled carbon nanotube-thermo-sensitive liposomes combined with near-infrared laser irradiation at 808 nm may potentially provide viable clinical strategies for targeting delivery of anti-cancer drugs. © The Author(s) 2014 Reprints and permissions: sagepub.co.uk/journalsPermissions.nav.

  19. Comparison of radiosensitivity and thermosensitivity among three types of cultured mammalian cells and detection of heat-induced cell killing by eosin-staining method

    Energy Technology Data Exchange (ETDEWEB)

    Kashiwado, Kouzou

    1988-12-01

    Radiosensitivity, Thermosensitivity and their combined sensitivity on cell death were studied using mouse L5178Y, mouse FM3A and human Burkitt lymphoma. Eosin-staining method was tested for counting the heat-induced dead cells. The results obtained in the present study were as follows: (1) In irradiation with /sup 60/Co gamma-rays D/sub 0/ values of 1.3 Gy, 1.4 Gy and 1.7 Gy were obtained for Burkitt lymphoma, L5178Y and FM3A respectively. (2) By heating at 43degC, T/sub 0/ values of 4.1 min, 12.5 min and 32 min were obtained for L5178Y, FM3A and Burkitt lymphoma respectively. (3) Thermotolerance decay depended on cell doubling time, that is, the shorter the doubling time, the faster the decay. Furthermore, the cell line with the higher thermosensitivity showed a faster decay of thermotolerance for the three cell lines used in the present study. (4) The radiosensitizing effects were nearly the same in all three cell lines. (5) Using eosin-staining method, the cell survival curves after hyperthermia were ascertained and compared with those obtained by colony forming method. In L5178Y the survival curves obtained by the two methods were nearly the same. In FM3A only some correlation was found betweewn the cell survival curves obtained by the two methods but in Burkitt lymphoma no correlation was found. (author) 52 refs.

  20. Comparison of radiosensitivity and thermosensitivity among three types of cultured mammalian cells and detection of heat-induced cell killing by eosin-staining method

    International Nuclear Information System (INIS)

    Kashiwado, Kouzou

    1988-01-01

    Radiosensitivity, Thermosensitivity and their combined sensitivity on cell death were studied using mouse L5178Y, mouse FM3A and human Burkitt lymphoma. Eosin-staining method was tested for counting the heat-induced dead cells. The results obtained in the present study were as follows: 1) In irradiation with 60 Co gamma-rays D 0 values of 1.3 Gy, 1.4 Gy and 1.7 Gy were obtained for Burkitt lymphoma, L5178Y and FM3A respectively. 2) By heating at 43degC, T 0 values of 4.1 min, 12.5 min and 32 min were obtained for L5178Y, FM3A and Burkitt lymphoma respectively. 3) Thermotolerance decay depended on cell doubling time, that is, the shorter the doubling time, the faster the decay. Furthermore, the cell line with the higher thermosensitivity showed a faster decay of thermotolerance for the three cell lines used in the present study. 4) The radiosensitizing effects were nearly the same in all three cell lines. 5) Using eosin-staining method, the cell survival curves after hyperthermia were ascertained and compared with those obtained by colony forming method. In L5178Y the survival curves obtained by the two methods were nearly the same. In FM3A only some correlation was found betweewn the cell survival curves obtained by the two methods but in Burkitt lymphoma no correlation was found. (author) 52 refs

  1. Electrophysiological evidence for voltage-gated calcium channel 2 (Cav2) modulation of mechano- and thermosensitive spinal neuronal responses in a rat model of osteoarthritis.

    Science.gov (United States)

    Rahman, W; Patel, R; Dickenson, A H

    2015-10-01

    Osteoarthritis (OA) remains one of the greatest healthcare burdens in western society, with chronic debilitating pain-dominating clinical presentation yet therapeutic strategies are inadequate in many patients. Development of better analgesics is contingent on improved understanding of the molecular mechanisms mediating OA pain. Voltage-gated calcium channels 2.2 (Cav2.2) play a critical role in spinal nociceptive transmission, therefore blocking Cav2.2 activity represents an attractive opportunity for OA pain treatment, but the only available licensed Cav2.2 antagonist ziconitide (PrilatTM) is of limited use. TROX-1 is an orally available, use dependent and state-selective Cav2 antagonist, exerting its analgesic effect primarily via Cav2.2 blockade, with an improved therapeutic window compared with ziconitide. Using a rat model of monosodium iodoacetate (MIA), 2 mg, induced OA we used in vivo electrophysiology to assess the effects of spinal or systemic administration of TROX-1 on the evoked activity of wide dynamic range spinal dorsal horn neurons in response to electrical, natural mechanical (dynamic brush and von Frey 2, 8, 26 and 6 g) and thermal (40, 45 and 45 °C) stimuli applied to the peripheral receptive field. MIA injection into the knee joint resulted in mechanical hypersensitivity of the ipsilateral hind paw and weight-bearing asymmetry. Spinal administration of TROX-1 (0.1 and 1 μg/50 μl) produced a significant dose-related inhibition of dynamic brush, mechanical (von Frey filament (vF) 8, 26 and 60 g) and noxious thermal-(45 and 48 °C) evoked neuronal responses in MIA rats only. Systemic administration of TROX-1 produced a significant inhibition of the mechanical-(vF 8, 26 and 60 g) evoked neuronal responses in MIA rats. TROX-1 did not produce any significant effect on any neuronal measure in Sham controls. Our in vivo electrophysiological results demonstrate a pathological state-dependent effect of TROX-1, which suggests an increased functional

  2. Effects of ambient temperature on sleep and cardiovascular regulation in mice: the role of hypocretin/orexin neurons.

    Directory of Open Access Journals (Sweden)

    Viviana Lo Martire

    Full Text Available The central neural pathways underlying the physiological coordination between thermoregulation and the controls of the wake-sleep behavior and cardiovascular function remain insufficiently understood. Growing evidence supports the involvement of hypocretin (orexin peptides in behavioral, cardiovascular, and thermoregulatory functions. We investigated whether the effects of ambient temperature on wake-sleep behavior and cardiovascular control depend on the hypothalamic neurons that release hypocretin peptides. Orexin-ataxin3 transgenic mice with genetic ablation of hypocretin neurons (n = 11 and wild-type controls (n = 12 were instrumented with electrodes for sleep scoring and a telemetric blood pressure transducer. Simultaneous sleep and blood pressure recordings were performed on freely-behaving mice at ambient temperatures ranging between mild cold (20°C and the thermoneutral zone (30°C. In both mouse groups, the time spent awake and blood pressure were higher at 20°C than at 30°C. The cold-related increase in blood pressure was significantly smaller in rapid-eye-movement sleep (REMS than either in non-rapid-eye-movement sleep (NREMS or wakefulness. Blood pressure was higher in wakefulness than either in NREMS or REMS at both ambient temperatures. This effect was significantly blunted in orexin-ataxin3 mice irrespective of ambient temperature and particularly during REMS. These data demonstrate that hypocretin neurons are not a necessary part of the central pathways that coordinate thermoregulation with wake-sleep behavior and cardiovascular control. Data also support the hypothesis that hypocretin neurons modulate changes in blood pressure between wakefulness and the sleep states. These concepts may have clinical implications in patients with narcolepsy with cataplexy, who lack hypocretin neurons.

  3. Effects of ambient temperature on sleep and cardiovascular regulation in mice: the role of hypocretin/orexin neurons.

    Science.gov (United States)

    Lo Martire, Viviana; Silvani, Alessandro; Bastianini, Stefano; Berteotti, Chiara; Zoccoli, Giovanna

    2012-01-01

    The central neural pathways underlying the physiological coordination between thermoregulation and the controls of the wake-sleep behavior and cardiovascular function remain insufficiently understood. Growing evidence supports the involvement of hypocretin (orexin) peptides in behavioral, cardiovascular, and thermoregulatory functions. We investigated whether the effects of ambient temperature on wake-sleep behavior and cardiovascular control depend on the hypothalamic neurons that release hypocretin peptides. Orexin-ataxin3 transgenic mice with genetic ablation of hypocretin neurons (n = 11) and wild-type controls (n = 12) were instrumented with electrodes for sleep scoring and a telemetric blood pressure transducer. Simultaneous sleep and blood pressure recordings were performed on freely-behaving mice at ambient temperatures ranging between mild cold (20°C) and the thermoneutral zone (30°C). In both mouse groups, the time spent awake and blood pressure were higher at 20°C than at 30°C. The cold-related increase in blood pressure was significantly smaller in rapid-eye-movement sleep (REMS) than either in non-rapid-eye-movement sleep (NREMS) or wakefulness. Blood pressure was higher in wakefulness than either in NREMS or REMS at both ambient temperatures. This effect was significantly blunted in orexin-ataxin3 mice irrespective of ambient temperature and particularly during REMS. These data demonstrate that hypocretin neurons are not a necessary part of the central pathways that coordinate thermoregulation with wake-sleep behavior and cardiovascular control. Data also support the hypothesis that hypocretin neurons modulate changes in blood pressure between wakefulness and the sleep states. These concepts may have clinical implications in patients with narcolepsy with cataplexy, who lack hypocretin neurons.

  4. Inhibition of TRPM8 channels reduces pain in the cold pressor test in humans.

    Science.gov (United States)

    Winchester, Wendy J; Gore, Katrina; Glatt, Sophie; Petit, Wendy; Gardiner, Jennifer C; Conlon, Kelly; Postlethwaite, Michael; Saintot, Pierre-Philippe; Roberts, Sonia; Gosset, James R; Matsuura, Tomomi; Andrews, Mark D; Glossop, Paul A; Palmer, Michael J; Clear, Nicola; Collins, Susie; Beaumont, Kevin; Reynolds, David S

    2014-11-01

    The transient receptor potential (subfamily M, member 8; TRPM8) is a nonselective cation channel localized in primary sensory neurons, and is a candidate for cold thermosensing, mediation of cold pain, and bladder overactivity. Studies with TRPM8 knockout mice and selective TRPM8 channel blockers demonstrate a lack of cold sensitivity and reduced cold pain in various rodent models. Furthermore, TRPM8 blockers significantly lower body temperature. We have identified a moderately potent (IC50 = 103 nM), selective TRPM8 antagonist, PF-05105679 [(R)-3-[(1-(4-fluorophenyl)ethyl)(quinolin-3-ylcarbonyl)amino]methylbenzoic acid]. It demonstrated activity in vivo in the guinea pig bladder ice water and menthol challenge tests with an IC50 of 200 nM and reduced core body temperature in the rat (at concentrations >1219 nM). PF-05105679 was suitable for acute administration to humans and was evaluated for effects on core body temperature and experimentally induced cold pain, using the cold pressor test. Unbound plasma concentrations greater than the IC50 were achieved with 600- and 900-mg doses. The compound displayed a significant inhibition of pain in the cold pressor test, with efficacy equivalent to oxycodone (20 mg) at 1.5 hours postdose. No effect on core body temperature was observed. An unexpected adverse event (hot feeling) was reported, predominantly periorally, in 23 and 36% of volunteers (600- and 900-mg dose, respectively), which in two volunteers was nontolerable. In conclusion, this study supports a role for TRPM8 in acute cold pain signaling at doses that do not cause hypothermia. Copyright © 2014 by The American Society for Pharmacology and Experimental Therapeutics.

  5. Cold injuries.

    Science.gov (United States)

    Kruse, R J

    1995-01-01

    There are two categories of cold injury. The first is hypothermia, which is a systemic injury to cold, and the second is frostbite, which is a local injury. Throughout history, entire armies, from George Washington to the Germans on the Russian Front in World War II, have fallen prey to prolonged cold exposure. Cold injury is common and can occur in all seasons if ambient temperature is lower than the core body temperature. In the 1985 Boston Marathon, even though it was 76 degrees and sunny, there were 75 runners treated for hypothermia. In general, humans adapt poorly to cold exposure. Children are at particular risk because of their relatively greater surface area/body mass ratio, causing them to cool even more rapidly than adults. Because of this, the human's best defense against cold injury is to limit his/her exposure to cold and to dress appropriately. If cold injury has occurred and is mild, often simple passive rewarming such as dry blankets and a warm room are sufficient treatment.

  6. Computer Modelling of Functional Aspects of Noise in Endogenously Oscillating Neurons

    Science.gov (United States)

    Huber, M. T.; Dewald, M.; Voigt, K.; Braun, H. A.; Moss, F.

    1998-03-01

    Membrane potential oscillations are a widespread feature of neuronal activity. When such oscillations operate close to the spike-triggering threshold, noise can become an essential property of spike-generation. According to that, we developed a minimal Hodgkin-Huxley-type computer model which includes a noise term. This model accounts for experimental data from quite different cells ranging from mammalian cortical neurons to fish electroreceptors. With slight modifications of the parameters, the model's behavior can be tuned to bursting activity, which additionally allows it to mimick temperature encoding in peripheral cold receptors including transitions to apparently chaotic dynamics as indicated by methods for the detection of unstable periodic orbits. Under all conditions, cooperative effects between noise and nonlinear dynamics can be shown which, beyond stochastic resonance, might be of functional significance for stimulus encoding and neuromodulation.

  7. Thermo-controlled rheology of electro-assembled polyanionic polysaccharide (alginate) and polycationic thermo-sensitive polymers.

    Science.gov (United States)

    Niang, Pape Momar; Huang, Zhiwei; Dulong, Virginie; Souguir, Zied; Le Cerf, Didier; Picton, Luc

    2016-03-30

    Several thermo-sensitive polyelectrolyte complexes were prepared by ionic self-association between an anionic polysaccharide (alginate) and a monocationic copolymer (polyether amine, Jeffamine®-M2005) with a 'Low Critical Solubility Temperature' (LCST). We show that electro-association must be established below the aggregation temperature of the free Jeffamine®, after which the organization of the system is controlled by the thermo-association of Jeffamine® that was previously electro-associated with the alginate. Evidence for this comes primarily from the rheology in the semi-dilute region. Electro- and thermo-associative behaviours are optimal at a pH corresponding to maximum ionization of both compounds (around pH 7). High ionic strength could prevent the electro-association. The reversibility of the transition is possible only at temperatures lower than the LCST of Jeffamine®. Similar behaviour has been obtained with carboxymethyl cellulose (CMC), which suggests that this behaviour can be observed using a range of anionic polyelectrolytes. In contrast, no specific properties have been found for pullulan, which is a neutral polysaccharide. Copyright © 2015 Elsevier Ltd. All rights reserved.

  8. Expression of TRPM8 in the distal cerebrospinal fluid-contacting neurons in the brain mesencephalon of rats

    Directory of Open Access Journals (Sweden)

    Zhang Licai

    2009-03-01

    Full Text Available Abstract Background It has been shown that distal cerebrospinal fluid-contacting neurons (dCSF-CNs exist near the ventral midline of the midbrain aqueduct and also in the grey matter of the inferior third ventricle and the fourth ventricle floor in the superior segment of the pons. The dCSF-CNs communicate between the cerebrospinal fluid (CSF and the brain parenchyma and may participate in the transduction and regulation of pain signals. The cold sensation receptor channel, TRPM8 is involved in analgesia for neuropathic pain, but whether the TRPM8 receptor exists on dCSF-CNs remains unknown. However, there is preliminary evidence that TRPM8 is expressed in dCSF-CNs and may participate in the transmission and regulation of sensory information between brain parenchyma and cerebrospinal fluid (CSF in rats. Methods Retrograde tracing of the cholera toxin subunit B labeled with horseradish peroxidase (CB-HRP injected into the lateral ventricle was used to identify dCSF-CNs. A double-labeled immunofluorescent technique and laser scanning confocal microscopy were used to identify the expression of TRPM8 in dCSF-CNs. Software Image-Pro Plus was used to count the number of neurons in three sections where CB-HRP positive neurons were located in the mesencephalon of six rats. Results The cell bodies of CB-HRP-positive dCSF-CNs were found in the brain parenchyma near the midline of the ventral Aq, also in the grey of the 3V, and the 4V floor in the superior segment of the pons. In the mesencephalon their processes extended into the CSF. TRPM8 labeled neurons were also found in the same area as were CB-HRP/TRPM8 double-labeled neurons. CB-HRP/TRPM8 double-labeled neurons were found in 42.9 ± 2.3% of neurons labeled by TRPM8, and all CB-HRP-labeled neurons were also labeled with TPRM8. Conclusion This study has demonstrated that the cold sensation receptor channel, TRPM8, is localised within the dCSF-CNs of the mesencephalon. TRPM8 acts as receptor of d

  9. Molecular dynamics simulation of the thermosensitivity of the human connexin 26 hemichannel

    Science.gov (United States)

    Alizadeh, Hadi; Davoodi, Jamal; Zeilinger, Carsten; Rafii-Tabar, Hashem

    2018-01-01

    Connexin hemichannels mediate cytoplasm and extracellular milieu communication by exchanging a variety of cytoplasmic molecules and ions. These hemichannels can be regulated by external stimuli such as mechanical stress, applied voltage, pH and temperature changes. Although there are many studies on structures and functions of connexin 26 in contexts of pH, ion concentration and voltage, employing computational methods, no such study has been performed so far involving temperature changes. In this study, using molecular dynamics simulation, we investigate thermosensitivity of the human Connexin 26 hemichannel. Our results show that the channel approaches a structurally closed state at lower temperature compared to higher temperature. This is in fair agreement with experimental results that indicate channel closure at lower temperature. Furthermore, our MD simulation results show that some regions of connexin 26 hemichannel are more sensitive to temperature compared to other regions. Whereas the intercellular half of the channel does not show any considerable response to temperature during the simulation time accessible in this study, the cytoplasmic half approaches a closed structural state at lower temperature compared to the higher temperature. Specifically, our results suggest that the cytoplasmic loop, the cytoplasmic half of the second transmembrane helix, and the N-terminus helix play a dominant role in temperature gating.

  10. Specific regulation of thermosensitive lipid droplet fusion by a nuclear hormone receptor pathway.

    Science.gov (United States)

    Li, Shiwei; Li, Qi; Kong, Yuanyuan; Wu, Shuang; Cui, Qingpo; Zhang, Mingming; Zhang, Shaobing O

    2017-08-15

    Nuclear receptors play important roles in regulating fat metabolism and energy production in humans. The regulatory functions and endogenous ligands of many nuclear receptors are still unidentified, however. Here, we report that CYP-37A1 (ortholog of human cytochrome P450 CYP4V2), EMB-8 (ortholog of human P450 oxidoreductase POR), and DAF-12 (homolog of human nuclear receptors VDR/LXR) constitute a hormone synthesis and nuclear receptor pathway in Caenorhabditis elegans This pathway specifically regulates the thermosensitive fusion of fat-storing lipid droplets. CYP-37A1, together with EMB-8, synthesizes a lipophilic hormone not identical to Δ7-dafachronic acid, which represses the fusion-promoting function of DAF-12. CYP-37A1 also negatively regulates thermotolerance and lifespan at high temperature in a DAF-12-dependent manner. Human CYP4V2 can substitute for CYP-37A1 in C. elegans This finding suggests the existence of a conserved CYP4V2-POR-nuclear receptor pathway that functions in converting multilocular lipid droplets to unilocular ones in human cells; misregulation of this pathway may lead to pathogenic fat storage.

  11. Transient receptor potential cation channel, subfamily C, member 5 (TRPC5) is a cold-transducer in the peripheral nervous system.

    Science.gov (United States)

    Zimmermann, Katharina; Lennerz, Jochen K; Hein, Alexander; Link, Andrea S; Kaczmarek, J Stefan; Delling, Markus; Uysal, Serdar; Pfeifer, John D; Riccio, Antonio; Clapham, David E

    2011-11-01

    Detection and adaptation to cold temperature is crucial to survival. Cold sensing in the innocuous range of cold (>10-15 °C) in the mammalian peripheral nervous system is thought to rely primarily on transient receptor potential (TRP) ion channels, most notably the menthol receptor, TRPM8. Here we report that TRP cation channel, subfamily C member 5 (TRPC5), but not TRPC1/TRPC5 heteromeric channels, are highly cold sensitive in the temperature range 37-25 °C. We found that TRPC5 is present in mouse and human sensory neurons of dorsal root ganglia, a substantial number of peripheral nerves including intraepithelial endings, and in the dorsal lamina of the spinal cord that receives sensory input from the skin, consistent with a potential TRPC5 function as an innocuous cold transducer in nociceptive and thermosensory nerve endings. Although deletion of TRPC5 in 129S1/SvImJ mice resulted in no temperature-sensitive behavioral changes, TRPM8 and/or other menthol-sensitive channels appear to underpin a much larger component of noxious cold sensing after TRPC5 deletion and a shift in mechanosensitive C-fiber subtypes. These findings demonstrate that highly cold-sensitive TRPC5 channels are a molecular component for detection and regional adaptation to cold temperatures in the peripheral nervous system that is distinct from noxious cold sensing.

  12. Bidirectional shifts of TRPM8 channel gating by temperature and chemical agents modulate the cold sensitivity of mammalian thermoreceptors.

    Science.gov (United States)

    Mälkiä, Annika; Madrid, Rodolfo; Meseguer, Victor; de la Peña, Elvira; Valero, María; Belmonte, Carlos; Viana, Félix

    2007-05-15

    TRPM8, a member of the melastatin subfamily of transient receptor potential (TRP) cation channels, is activated by voltage, low temperatures and cooling compounds. These properties and its restricted expression to small sensory neurons have made it the ion channel with the most advocated role in cold transduction. Recent work suggests that activation of TRPM8 by cold and menthol takes place through shifts in its voltage-activation curve, which cause the channel to open at physiological membrane potentials. By contrast, little is known about the actions of inhibitors on the function of TRPM8. We investigated the chemical and thermal modulation of TRPM8 in transfected HEK293 cells and in cold-sensitive primary sensory neurons. We show that cold-evoked TRPM8 responses are effectively suppressed by inhibitor compounds SKF96365, 4-(3-chloro-pyridin-2-yl)-piperazine-1-carboxylic acid (4-tert-butyl-phenyl)-amide (BCTC) and 1,10-phenanthroline. These antagonists exert their effect by shifting the voltage dependence of TRPM8 activation towards more positive potentials. An opposite shift towards more negative potentials is achieved by the agonist menthol. Functionally, the bidirectional shift in channel gating translates into a change in the apparent temperature threshold of TRPM8-expressing cells. Accordingly, in the presence of the antagonist compounds, the apparent response-threshold temperature of TRPM8 is displaced towards colder temperatures, whereas menthol sensitizes the response, shifting the threshold in the opposite direction. Co-application of agonists and antagonists produces predictable cancellation of these effects, suggesting the convergence on a common molecular process. The potential for half maximal activation of TRPM8 activation by cold was approximately 140 mV more negative in native channels compared to recombinant channels, with a much higher open probability at negative membrane potentials in the former. In functional terms, this difference translates

  13. Cold plate

    Energy Technology Data Exchange (ETDEWEB)

    Marroquin, Christopher M.; O' Connell, Kevin M.; Schultz, Mark D.; Tian, Shurong

    2018-02-13

    A cold plate, an electronic assembly including a cold plate, and a method for forming a cold plate are provided. The cold plate includes an interface plate and an opposing plate that form a plenum. The cold plate includes a plurality of active areas arranged for alignment over respective heat generating portions of an electronic assembly, and non-active areas between the active areas. A cooling fluid flows through the plenum. The plenum, at the non-active areas, has a reduced width and/or reduced height relative to the plenum at the active areas. The reduced width and/or height of the plenum, and exterior dimensions of cold plate, at the non-active areas allow the non-active areas to flex to accommodate surface variations of the electronics assembly. The reduced width and/or height non-active areas can be specifically shaped to fit between physical features of the electronics assembly.

  14. Microwave based synthesis and spectral characterization of thermo-sensitive poly(N,N-diethylacrylamide) grafted pectin copolymer.

    Science.gov (United States)

    Işıklan, Nuran; Tokmak, Şeyma

    2018-07-01

    The functionalization of polysaccharides with synthetic polymers has attracted great attention owing to its application in many industrial fields. The aim of this work was to study the impact of pectin functionalization with N,N-diethylacrylamide (DEAAm). Pectin was modified via microwave-induced graft copolymerization of DEAAm using ceric ammonium nitrate (CAN) and N,N,N',N'-tetramethylethylenediamine (TEMED). FTIR, 13 C NMR, DSC/TGA, XRD, and SEM techniques were used to verify the structure of graft copolymers. Various reaction conditions such as microwave irradiation time, temperature, microwave power, monomer, initiator, and TEMED concentrations were investigated to get a maximum grafting yield of 192%. Lower critical solution temperatures (LCST) of graft copolymers were determined by UV spectroscopy. Graft copolymers were found to be thermo-sensitive, with LCST of 31°C and high thermal resistance. Biocompatibility test of copolymers showed that copolymers were not cytotoxic to L929 fibroblasts cells and can be used as a biomaterial. Copyright © 2018 Elsevier B.V. All rights reserved.

  15. Conceptualizing Cold Disasters

    DEFF Research Database (Denmark)

    Lauta, Kristian Cedervall; Dahlberg, Rasmus; Vendelø, Morten Thanning

    2017-01-01

    In the present article, we explore in more depth the particular circumstances and characteristics of governing what we call ‘cold disasters’, and thereby, the paper sets out to investigate how disasters in cold contexts distinguish themselves from other disasters, and what the implications hereof...... are for the conceptualization and governance of cold disasters. Hence, the paper can also be viewed as a response to Alexander’s (2012a) recent call for new theory in the field of disaster risk reduction. The article is structured in four overall parts. The first part, Cold Context, provides an overview of the specific...... conditions in a cold context, exemplified by the Arctic, and zooms in on Greenland to provide more specific background for the paper. The second part, Disasters in Cold Contexts, discusses “cold disasters” in relation to disaster theory, in order to, elucidate how cold disasters challenge existing...

  16. NeuronBank: a tool for cataloging neuronal circuitry

    Directory of Open Access Journals (Sweden)

    Paul S Katz

    2010-04-01

    Full Text Available The basic unit of any nervous system is the neuron. Therefore, understanding the operation of nervous systems ultimately requires an inventory of their constituent neurons and synaptic connectivity, which form neural circuits. The presence of uniquely identifiable neurons or classes of neurons in many invertebrates has facilitated the construction of cellular-level connectivity diagrams that can be generalized across individuals within a species. Homologous neurons can also be recognized across species. Here we describe NeuronBank.org, a web-based tool that we are developing for cataloging, searching, and analyzing neuronal circuitry within and across species. Information from a single species is represented in an individual branch of NeuronBank. Users can search within a branch or perform queries across branches to look for similarities in neuronal circuits across species. The branches allow for an extensible ontology so that additional characteristics can be added as knowledge grows. Each entry in NeuronBank generates a unique accession ID, allowing it to be easily cited. There is also an automatic link to a Wiki page allowing an encyclopedic explanation of the entry. All of the 44 previously published neurons plus one previously unpublished neuron from the mollusc, Tritonia diomedea, have been entered into a branch of NeuronBank as have 4 previously published neurons from the mollusc, Melibe leonina. The ability to organize information about neuronal circuits will make this information more accessible, ultimately aiding research on these important models.

  17. Isolation of TRPV1 independent mechanisms of spontaneous and asynchronous glutamate release at primary afferent to NTS synapses.

    Directory of Open Access Journals (Sweden)

    Axel J. Fenwick

    2014-01-01

    Full Text Available Cranial visceral afferents contained within the solitary tract (ST contact second-order neurons in the nucleus of the solitary tract (NTS and release the excitatory amino acid glutamate via three distinct exocytosis pathways; synchronous, asynchronous, and spontaneous release. The presence of TRPV1 in the central terminals of a majority of ST afferents conveys activity-dependent asynchronous glutamate release and provides a temperature sensitive calcium conductance which largely determines the rate of spontaneous vesicle fusion. TRPV1 is present in unmyelinated C-fiber afferents and these facilitated forms of glutamate release may underlie the relative strength of C-fibers in activating autonomic reflex pathways. However, pharmacological blockade of TRPV1 signaling eliminates only ~50% of the asynchronous profile and attenuates the temperature sensitivity of spontaneous release indicating additional thermosensitive calcium influx pathways may exist which mediate these forms of vesicle release. In the present study we isolate the contribution of TRPV1 independent forms of glutamate release at ST-NTS synapses. We found ST afferent innervation at NTS neurons and synchronous vesicle release from TRPV1 KO mice was not different to control animals; however, only half of TRPV1 KO ST afferents completely lacked asynchronous glutamate release. Further, temperature driven spontaneous rates of vesicle release were not different from 33˚ - 37˚C between control and TRPV1 KO afferents. These findings suggest additional temperature dependent mechanisms controlling asynchronous and thermosensitive spontaneous release at physiological temperatures, possibly mediated by additional thermosensitive TRP channels in primary afferent terminals.

  18. Progranulin overexpression in sensory neurons attenuates neuropathic pain in mice: Role of autophagy.

    Science.gov (United States)

    Altmann, Christine; Hardt, Stefanie; Fischer, Caroline; Heidler, Juliana; Lim, Hee-Young; Häussler, Annett; Albuquerque, Boris; Zimmer, Béla; Möser, Christine; Behrends, Christian; Koentgen, Frank; Wittig, Ilka; Schmidt, Mirko H H; Clement, Albrecht M; Deller, Thomas; Tegeder, Irmgard

    2016-12-01

    Peripheral or central nerve injury is a frequent cause of chronic pain and the mechanisms are not fully understood. Using newly generated transgenic mice we show that progranulin overexpression in sensory neurons attenuates neuropathic pain after sciatic nerve injury and accelerates nerve healing. A yeast-2-hybrid screen revealed putative interactions of progranulin with autophagy-related proteins, ATG12 and ATG4b. This was supported by colocalization and proteomic studies showing regulations of ATG13 and ATG4b and other members of the autophagy network, lysosomal proteins and proteins involved in endocytosis. The association of progranulin with the autophagic pathway was functionally confirmed in primary sensory neurons. Autophagy and survival were impaired in progranulin-deficient neurons and improved in progranulin overexpressing neurons. Nerve injury in vivo caused an accumulation of LC3b-EGFP positive bodies in neurons of the dorsal root ganglia and nerves suggesting an impairment of autophagic flux. Overexpression of progranulin in these neurons was associated with a reduction of the stress marker ATF3, fewer protein aggregates in the injured nerve and enhanced stump healing. At the behavioral level, further inhibition of the autophagic flux by hydroxychloroquine intensified cold and heat nociception after sciatic nerve injury and offset the pain protection provided by progranulin. We infer that progranulin may assist in removal of protein waste and thereby helps to resolve neuropathic pain after nerve injury. Copyright © 2016 Elsevier Inc. All rights reserved.

  19. Cold urticaria. Dissociation of cold-evoked histamine release and urticara following cold challenge.

    Science.gov (United States)

    Keahey, T M; Greaves, M W

    1980-02-01

    Nine patients with acquired cold urticaria were studied to assess the effects of beta-adrenergic agents, xanthines, and corticosteroids on cold-evoked histamine release from skin in vivo. The patients, in all of whom an immediate urticarial response developed after cooling of the forearm, demonstrated release of histamine into the venous blood draining that forearm. Following treatment with aminophylline and albuterol in combination or prednisone alone, suppression of histamine release occurred in all but one patient. In some patients, this was accompanied by a subjective diminution in pruritus or buring, but there was no significant improvement in the ensuing edema or erythema. In one patient, total suppression of histamine release was achieved without any effect on whealing and erythema in response to cold challenge. Our results suggest that histamine is not central to the pathogenesis of vascular changes in acquired cold urticaria.

  20. Extraction Separation of Am(III) and Eu(III) with Thermo-sensitive Gel introducing TPEN Derivatives

    International Nuclear Information System (INIS)

    Kenji Takeshita; Yoshio Nakano; Tatsuro Matsumura; Atsunori Mori

    2008-01-01

    A thermal-swing chromatographic process using a thermo-sensitive gel co-polymerized with NIPA (N-isopropyl-acrylamide) and TPPEN (N,N,N',N'-tetrakis(4-propenyl-oxy-2-pyridyl-methyl)ethylenediamine) was studied for the separation of Am(III) from Eu(III). First, the radiolysis of the TPPEN-NIPA gel was tested by the γ-ray irradiation and the α nuclide adsorption. The extraction separation of Am(III) was not influenced in the radioactive environment of the proposed process. Next, the TPPEN-NIPA gel was immobilized in porous silica particles and the applicability of the gel-immobilized silica to the proposed process was tested. Am(III) was extracted selectively in the gel-immobilized silica at 5 deg. C and the separation factor of Am(III) over Eu(III) was evaluated to be 3.7. The distribution ratio of Am(III) was reduced to less than 1/20 by increasing temperature from 5 deg. C to 40 deg. C. These results indicate that the TPPEN-NIPA gel is applicable to the thermal-swing chromatographic process for the minor actinide recovery. (authors)

  1. Relationships of self-identified cold tolerance and cold-induced vasodilatation in the finger

    Science.gov (United States)

    Park, Joonhee; Lee, Joo-Young

    2016-04-01

    This study was conducted to investigate relationships of self-identified cold tolerance and cold-induced vasodilatation (CIVD) in the finger. Nine males and 34 females participated in the following 2 tests: a CIVD test and a self-reported survey. The CIVD test was conducted 30-min cold-water immersion (3.8 ± 0.3 °C) of the middle finger at an air temperature of 27.9 ± 0.1 °C. The self-reported questionnaire consisted of 28 questions about whole and local body cold and heat tolerances. By a cluster analysis on the survey results, the participants were divided into two groups: high self-identified cold tolerance (HSCT, n = 25) and low self-identified cold tolerance (LSCT, n = 18). LSCT had lower self-identified cold tolerance ( P cold or heat tolerance had relationships with cold tolerance index, T max, and amplitude ( P cold tolerance classified through a standardized survey could be a good index to predict physiological cold tolerance.

  2. Functional Loss of Bmsei Causes Thermosensitive Epilepsy in Contractile Mutant Silkworm, Bombyx mori

    Science.gov (United States)

    Nie, Hongyi; Cheng, Tingcai; Huang, Xiaofeng; Zhou, Mengting; Zhang, Yinxia; Dai, Fangyin; Mita, Kazuei; Xia, Qingyou; Liu, Chun

    2015-07-01

    The thermoprotective mechanisms of insects remain largely unknown. We reported the Bombyx mori contractile (cot) behavioral mutant with thermo-sensitive seizures phenotype. At elevated temperatures, the cot mutant exhibit seizures associated with strong contractions, rolling, vomiting, and a temporary lack of movement. We narrowed a region containing cot to ~268 kb by positional cloning and identified the mutant gene as Bmsei which encoded a potassium channel protein. Bmsei was present in both the cell membrane and cytoplasm in wild-type ganglia but faint in cot. Furthermore, Bmsei was markedly decreased upon high temperature treatment in cot mutant. With the RNAi method and injecting potassium channel blockers, the wild type silkworm was induced the cot phenotype. These results demonstrated that Bmsei was responsible for the cot mutant phenotype and played an important role in thermoprotection in silkworm. Meanwhile, comparative proteomic approach was used to investigate the proteomic differences. The results showed that the protein of Hsp-1 and Tn1 were significantly decreased and increased on protein level in cot mutant after thermo-stimulus, respectively. Our data provide insights into the mechanism of thermoprotection in insect. As cot phenotype closely resembles human epilepsy, cot might be a potential model for the mechanism of epilepsy in future.

  3. Effect of acute lateral hemisection of the spinal cord on spinal neurons of postural networks

    Science.gov (United States)

    Zelenin, P. V.; Lyalka, V. F.; Orlovsky, G. N.; Deliagina, T. G.

    2016-01-01

    In quadrupeds, acute lateral hemisection of the spinal cord (LHS) severely impairs postural functions, which recover over time. Postural limb reflexes (PLRs) represent a substantial component of postural corrections in intact animals. The aim of the present study was to characterize the effects of acute LHS on two populations of spinal neurons (F and E) mediating PLRs. For this purpose, in decerebrate rabbits, responses of individual neurons from L5 to stimulation causing PLRs were recorded before and during reversible LHS (caused by temporal cold block of signal transmission in lateral spinal pathways at L1), as well as after acute surgical (Sur) LHS at L1. Results obtained after Sur-LHS were compared to control data obtained in our previous study. We found that acute LHS caused disappearance of PLRs on the affected side. It also changed a proportion of different types of neurons on that side. A significant decrease and increase in the proportion of F- and non-modulated neurons, respectively, was found. LHS caused a significant decrease in most parameters of activity in F-neurons located in the ventral horn on the lesioned side and in E-neurons of the dorsal horn on both sides. These changes were caused by a significant decrease in the efficacy of posture-related sensory input from the ipsilateral limb to F-neurons, and from the contralateral limb to both F- and E-neurons. These distortions in operation of postural networks underlie the impairment of postural control after acute LHS, and represent a starting point for the subsequent recovery of postural functions. PMID:27702647

  4. Kappe neurons, a novel population of olfactory sensory neurons.

    Science.gov (United States)

    Ahuja, Gaurav; Bozorg Nia, Shahrzad; Zapilko, Veronika; Shiriagin, Vladimir; Kowatschew, Daniel; Oka, Yuichiro; Korsching, Sigrun I

    2014-02-10

    Perception of olfactory stimuli is mediated by distinct populations of olfactory sensory neurons, each with a characteristic set of morphological as well as functional parameters. Beyond two large populations of ciliated and microvillous neurons, a third population, crypt neurons, has been identified in teleost and cartilaginous fishes. We report here a novel, fourth olfactory sensory neuron population in zebrafish, which we named kappe neurons for their characteristic shape. Kappe neurons are identified by their Go-like immunoreactivity, and show a distinct spatial distribution within the olfactory epithelium, similar to, but significantly different from that of crypt neurons. Furthermore, kappe neurons project to a single identified target glomerulus within the olfactory bulb, mdg5 of the mediodorsal cluster, whereas crypt neurons are known to project exclusively to the mdg2 glomerulus. Kappe neurons are negative for established markers of ciliated, microvillous and crypt neurons, but appear to have microvilli. Kappe neurons constitute the fourth type of olfactory sensory neurons reported in teleost fishes and their existence suggests that encoding of olfactory stimuli may require a higher complexity than hitherto assumed already in the peripheral olfactory system.

  5. Burning Cold: Involvement of TRPA1 in Noxious Cold Sensation

    OpenAIRE

    Kwan, Kelvin Y.; Corey, David P.

    2009-01-01

    Soon after its discovery ten years ago, the ion channel TRPA1 was proposed as a sensor of noxious cold. Evidence for its activation by painfully cold temperatures (below ~15° C) has been mixed, however. Some groups found that cold elicits a nonselective conductance in cells expressing TRPA1; others found no activation, or argued that activation is an indirect effect of elevated \\(Ca^{ 2+}\\) . Sensory cells from the trigeminal and dorsal root ganglia that are activated by cold were sometimes c...

  6. Cold-Hearted or Cool-Headed: Physical Coldness Promotes Utilitarian Moral Judgment

    Directory of Open Access Journals (Sweden)

    Hiroko eNakamura

    2014-10-01

    Full Text Available In the current study, we examine the effect of physical coldness on personal moral dilemma judgment. Previous studies have indicated that utilitarian moral judgment—sacrificing a few people to achieve the greater good for others—was facilitated when: (1 participants suppressed an initial emotional response and deliberately thought about the utility of outcomes; (2 participants had a high-level construal mindset and focused on abstract goals (e.g., save many; or (3 there was a decreasing emotional response to sacrificing a few. In two experiments, we exposed participants to extreme cold or typical room temperature and then asked them to make personal moral dilemma judgments. The results of Experiment 1 indicated that coldness prompted utilitarian judgment, but the effect of coldness was independent from deliberate thought or abstract high-level construal mindset. As Experiment 2 revealed, coldness facilitated utilitarian judgment via reduced empathic feelings. Therefore, physical coldness did not affect the cool-headed deliberate process or the abstract high-level construal mindset. Rather, coldness biased people toward being cold-hearted, reduced empathetic concern about a sacrificed victim, and facilitated utilitarian moral judgments.

  7. Glut2-dependent glucose-sensing controls thermoregulation by enhancing the leptin sensitivity of NPY and POMC neurons.

    Science.gov (United States)

    Mounien, Lourdes; Marty, Nell; Tarussio, David; Metref, Salima; Genoux, David; Preitner, Frédéric; Foretz, Marc; Thorens, Bernard

    2010-06-01

    The physiological contribution of glucose in thermoregulation is not completely established nor whether this control may involve a regulation of the melanocortin pathway. Here, we assessed thermoregulation and leptin sensitivity of hypothalamic arcuate neurons in mice with inactivation of glucose transporter type 2 (Glut2)-dependent glucose sensing. Mice with inactivation of Glut2-dependent glucose sensors are cold intolerant and show increased susceptibility to food deprivation-induced torpor and abnormal hypothermic response to intracerebroventricular administration of 2-deoxy-d-glucose compared to control mice. This is associated with a defect in regulated expression of brown adipose tissue uncoupling protein I and iodothyronine deiodinase II and with a decreased leptin sensitivity of neuropeptide Y (NPY) and proopiomelanocortin (POMC) neurons, as observed during the unfed-to-refed transition or following i.p. leptin injection. Sites of central Glut-2 expression were identified by a genetic tagging approach and revealed that glucose-sensitive neurons were present in the lateral hypothalamus, the dorsal vagal complex, and the basal medulla but not in the arcuate nucleus. NPY and POMC neurons were, however, connected to nerve terminals from Glut2-expressing neurons. Thus, our data suggest that glucose controls thermoregulation and the leptin sensitivity of NPY and POMC neurons through activation of Glut2-dependent glucose-sensing neurons located outside of the arcuate nucleus.

  8. Kappe neurons, a novel population of olfactory sensory neurons

    OpenAIRE

    Ahuja, Gaurav; Nia, Shahrzad Bozorg; Zapilko, Veronika; Shiriagin, Vladimir; Kowatschew, Daniel; Oka, Yuichiro; Korsching, Sigrun I.

    2014-01-01

    Perception of olfactory stimuli is mediated by distinct populations of olfactory sensory neurons, each with a characteristic set of morphological as well as functional parameters. Beyond two large populations of ciliated and microvillous neurons, a third population, crypt neurons, has been identified in teleost and cartilaginous fishes. We report here a novel, fourth olfactory sensory neuron population in zebrafish, which we named kappe neurons for their characteristic shape. Kappe neurons ar...

  9. Grooved cold moderator tests

    International Nuclear Information System (INIS)

    Inoue, K.; Kiyanagi, Y.; Iwasa, H.; Watanabe, N.; Ikeda, S.; Carpenter, J.M.; Ishikawa, Y.

    1983-01-01

    We performed some grooved cold moderator experiments for methane at 20 K by using the Hokkaido University linac to obtain information to be used in the planning of the KENS-I' project. Cold neutron gains, spatial distribution of emitted beams and time distribution of the neutrons in the grooved cold moderator were measured. Furthermore, we assessed the effects of the grooved cold moderator on the performances of the spectrometers presently installed at the KENS-I cold source. We concluded that the grooved cold moderator benefited appreciably the performances of the spectrometers

  10. Thermo-sensitive and swelling properties of cellouronic acid sodium/poly (acrylamide-co-diallyldimethylammonium chloride) semi-IPN.

    Science.gov (United States)

    Zhang, Heng; Gao, Xin; Chen, Keli; Li, Hui; Peng, Lincai

    2018-02-01

    In current study, cellouronic acid sodium (CAS), obtained from bagasse pith, has been introduced into poly(acrylamide-co-diallyldimethylammonium chloride) (poly(AM-co-DAC)) network to form novel thermo-sensitive semi-IPNs. The structure and morphology of the hydrogels were proved by Fourier transformation infrared spectroscopy (FT-IR), X-ray photoelectron spectroscopy (XPS) and scanning electron microscopy (SEM). The effects of CAS content, initiator charge, cross-linker dosage and swelling-medium property on the thermo-responsive water absorptivity were investigated in detail. The results elucidated that the prepared gels exhibited a thermo-sensibility with an upper critical solution temperature (UCST) and a high water-absorbency. And the values of UCST and equilibrium swelling ratio largely depended on the inner structure of the semi-IPNs and the external solvent property. It was also revealed that the swelling process conformed to the Schott's pseudo second order model and diffusion type was non-Fickian diffusion. The value of activation energy for this polyelectrolyte was found to be 8.74kJ/mol. Copyright © 2017 Elsevier Ltd. All rights reserved.

  11. Body mapping of cutaneous wetness perception across the human torso during thermo-neutral and warm environmental exposures.

    Science.gov (United States)

    Filingeri, Davide; Fournet, Damien; Hodder, Simon; Havenith, George

    2014-10-15

    Sensing skin wetness is linked to inputs arising from cutaneous cold-sensitive afferents. As thermosensitivity to cold varies significantly across the torso, we investigated whether similar regional differences in wetness perception exist. We also investigated the regional differences in thermal pleasantness and whether these sensory patterns are influenced by ambient temperature. Sixteen males (20 ± 2 yr) underwent a quantitative sensory test under thermo-neutral [air temperature (Tair) = 22°C; relative humidity (RH) = 50%] and warm conditions (Tair = 33°C; RH = 50%). Twelve regions of the torso were stimulated with a dry thermal probe (25 cm(2)) with a temperature of 15°C below local skin temperature (Tsk). Variations in Tsk, thermal, wetness, and pleasantness sensations were recorded. As a result of the same cold-dry stimulus, the skin-cooling response varied significantly by location (P = 0.003). The lateral chest showed the greatest cooling (-5 ± 0.4°C), whereas the lower back showed the smallest (-1.9 ± 0.4°C). Thermal sensations varied significantly by location and independently from regional variations in skin cooling with colder sensations reported on the lateral abdomen and lower back. Similarly, the frequency of perceived skin wetness was significantly greater on the lateral and lower back as opposed to the medial chest. Overall wetness perception was slightly higher under warm conditions. Significantly more unpleasant sensations were recorded when the lateral abdomen and lateral and lower back were stimulated. We conclude that humans present regional differences in skin wetness perception across the torso, with a pattern similar to the regional differences in thermosensitivity to cold. These findings indicate the presence of a heterogeneous distribution of cold-sensitive thermo-afferent information. Copyright © 2014 the American Physiological Society.

  12. The transcription factor Nerfin-1 prevents reversion of neurons into neural stem cells.

    Science.gov (United States)

    Froldi, Francesca; Szuperak, Milan; Weng, Chen-Fang; Shi, Wei; Papenfuss, Anthony T; Cheng, Louise Y

    2015-01-15

    Cellular dedifferentiation is the regression of a cell from a specialized state to a more multipotent state and is implicated in cancer. However, the transcriptional network that prevents differentiated cells from reacquiring stem cell fate is so far unclear. Neuroblasts (NBs), the Drosophila neural stem cells, are a model for the regulation of stem cell self-renewal and differentiation. Here we show that the Drosophila zinc finger transcription factor Nervous fingers 1 (Nerfin-1) locks neurons into differentiation, preventing their reversion into NBs. Following Prospero-dependent neuronal specification in the ganglion mother cell (GMC), a Nerfin-1-specific transcriptional program maintains differentiation in the post-mitotic neurons. The loss of Nerfin-1 causes reversion to multipotency and results in tumors in several neural lineages. Both the onset and rate of neuronal dedifferentiation in nerfin-1 mutant lineages are dependent on Myc- and target of rapamycin (Tor)-mediated cellular growth. In addition, Nerfin-1 is required for NB differentiation at the end of neurogenesis. RNA sequencing (RNA-seq) and chromatin immunoprecipitation (ChIP) analysis show that Nerfin-1 administers its function by repression of self-renewing-specific and activation of differentiation-specific genes. Our findings support the model of bidirectional interconvertibility between neural stem cells and their post-mitotic progeny and highlight the importance of the Nerfin-1-regulated transcriptional program in neuronal maintenance. © 2015 Froldi et al.; Published by Cold Spring Harbor Laboratory Press.

  13. Vasculo-Neuronal Coupling: Retrograde Vascular Communication to Brain Neurons.

    Science.gov (United States)

    Kim, Ki Jung; Ramiro Diaz, Juan; Iddings, Jennifer A; Filosa, Jessica A

    2016-12-14

    Continuous cerebral blood flow is essential for neuronal survival, but whether vascular tone influences resting neuronal function is not known. Using a multidisciplinary approach in both rat and mice brain slices, we determined whether flow/pressure-evoked increases or decreases in parenchymal arteriole vascular tone, which result in arteriole constriction and dilation, respectively, altered resting cortical pyramidal neuron activity. We present evidence for intercellular communication in the brain involving a flow of information from vessel to astrocyte to neuron, a direction opposite to that of classic neurovascular coupling and referred to here as vasculo-neuronal coupling (VNC). Flow/pressure increases within parenchymal arterioles increased vascular tone and simultaneously decreased resting pyramidal neuron firing activity. On the other hand, flow/pressure decreases evoke parenchymal arteriole dilation and increased resting pyramidal neuron firing activity. In GLAST-CreERT2; R26-lsl-GCaMP3 mice, we demonstrate that increased parenchymal arteriole tone significantly increased intracellular calcium in perivascular astrocyte processes, the onset of astrocyte calcium changes preceded the inhibition of cortical pyramidal neuronal firing activity. During increases in parenchymal arteriole tone, the pyramidal neuron response was unaffected by blockers of nitric oxide, GABA A , glutamate, or ecto-ATPase. However, VNC was abrogated by TRPV4 channel, GABA B , as well as an adenosine A 1 receptor blocker. Differently to pyramidal neuron responses, increases in flow/pressure within parenchymal arterioles increased the firing activity of a subtype of interneuron. Together, these data suggest that VNC is a complex constitutive active process that enables neurons to efficiently adjust their resting activity according to brain perfusion levels, thus safeguarding cellular homeostasis by preventing mismatches between energy supply and demand. We present evidence for vessel-to-neuron

  14. Cold acclimation increases cold tolerance independently of diapause programing in the bean bug, Riptortus pedestris.

    Science.gov (United States)

    Rozsypal, J; Moos, M; Goto, S G

    2017-10-17

    The bean bug (Riptortus pedestris) is a pest of soybeans and other legumes in Japan and other Asian countries. It enters a facultative adult diapause on exposure to short days. While photoperiodism and diapause are well understood in R. pedestris, knowledge of cold tolerance is very limited, as is information on the effect of diapause on cold tolerance. We examined the effect of photoperiod, cold acclimation, and feeding status on cold tolerance in R. pedestris. We found that cold acclimation significantly increased survival at -10°C in both long- and short-day adult R. pedestris. Since the difference in cold survival between long- and short-day cold-acclimated groups was only marginal, we conclude that entering diapause is not crucial for R. pedestris to successfully pass through cold acclimation and become cold tolerant. We observed similar effects in 5th instar nymphs, with both long- and short-day cold-acclimated groups surviving longer cold exposures compared with non-acclimated groups. Starvation, which was tested only in adult bugs, had only a negligible and negative impact on cold survival. Although cold tolerance significantly increased with cold acclimation in adult bugs, supercooling capacity unexpectedly decreased. Our results suggest that changes in supercooling capacity as well as in water content are unrelated to cold tolerance in R. pedestris. An analysis of metabolites revealed differences between the treatments, and while several metabolites markedly increased with cold acclimation, their concentrations were too low to have a significant effect on cold tolerance.

  15. The thermosensitive TRPV3 channel contributes to rapid wound healing in oral epithelia.

    Science.gov (United States)

    Aijima, Reona; Wang, Bing; Takao, Tomoka; Mihara, Hiroshi; Kashio, Makiko; Ohsaki, Yasuyoshi; Zhang, Jing-Qi; Mizuno, Atsuko; Suzuki, Makoto; Yamashita, Yoshio; Masuko, Sadahiko; Goto, Masaaki; Tominaga, Makoto; Kido, Mizuho A

    2015-01-01

    The oral cavity provides an entrance to the alimentary tract to serve as a protective barrier against harmful environmental stimuli. The oral mucosa is susceptible to injury because of its location; nonetheless, it has faster wound healing than the skin and less scar formation. However, the molecular pathways regulating this wound healing are unclear. Here, we show that transient receptor potential vanilloid 3 (TRPV3), a thermosensitive Ca(2+)-permeable channel, is more highly expressed in murine oral epithelia than in the skin by quantitative RT-PCR. We found that temperatures above 33°C activated TRPV3 and promoted oral epithelial cell proliferation. The proliferation rate in the oral epithelia of TRPV3 knockout (TRPV3KO) mice was less than that of wild-type (WT) mice. We investigated the contribution of TRPV3 to wound healing using a molar tooth extraction model and found that oral wound closure was delayed in TRPV3KO mice compared with that in WT mice. TRPV3 mRNA was up-regulated in wounded tissues, suggesting that TRPV3 may contribute to oral wound repair. We identified TRPV3 as an essential receptor in heat-induced oral epithelia proliferation and wound healing. Our findings suggest that TRPV3 activation could be a potential therapeutic target for wound healing in skin and oral mucosa. © FASEB.

  16. Mechanically Enhanced Liquid Interfaces at Human Body Temperature Using Thermosensitive Methylated Nanocrystalline Cellulose.

    Science.gov (United States)

    Scheuble, N; Geue, T; Kuster, S; Adamcik, J; Mezzenga, R; Windhab, E J; Fischer, P

    2016-02-09

    The mechanical performance of materials at oil/water interfaces after consumption is a key factor affecting hydrophobic drug release. In this study, we methylated the surface of nanocrystalline cellulose (NCC) by mercerization and dimethyl sulfate exposure to produce thermosensitive biopolymers. These methylated NCC (metNCC) were used to investigate interfacial thermogelation at air/water and medium-chain triglyceride (MCT)/water interfaces at body temperature. In contrast to bulk fluid dynamics, elastic layers were formed at room temperature, and elasticity increased significantly at body temperature, which was measured by interfacial shear and dilatational rheology in situ. This unique phenomenon depends on solvent quality, temperature, and polymer concentration at interfaces. Thus, by adjusting the degree of hydrophobicity of metNCC, the interfacial elasticity and thermogelation of the interfaces could be varied. In general, these new materials (metNCC) formed more brittle interfacial layers compared to commercial methylcellulose (MC A15). Thermogelation of methylcellulose promotes attractive intermolecular forces, which were reflected in a change in self-assembly of metNCC at the interface. As a consequence, layer thickness and density increased as a function of temperature. These effects were measured by atomic force microscopy (AFM) images of the displaced interface and confirmed by neutron reflection. The substantial structural and mechanical change of methylcellulose interfaces at body temperature represents a controllable encapsulation parameter allowing optimization of lipid-based drug formulations.

  17. Synthesis of thermosensitive magnetic nanocarrier for controlled sorafenib delivery

    Energy Technology Data Exchange (ETDEWEB)

    Heidarinasab, Amir [Department of Chemical Engineering, Science and Research Branch, Islamic Azad University, Tehran (Iran, Islamic Republic of); Ahmad Panahi, Homayon [Department of Chemistry, Central Tehran Branch, Islamic Azad University, Tehran (Iran, Islamic Republic of); Faramarzi, Mehdi, E-mail: faramarzi.iaug@gmail.com [Department of Chemical Engineering, Science and Research Branch, Islamic Azad University, Tehran (Iran, Islamic Republic of); Farjadian, Fatemeh [Pharmaceutical Sciences Research Center, Faculty of Pharmacy, Shiraz University of Medical Sciences, Shiraz (Iran, Islamic Republic of)

    2016-10-01

    Allyl glycidyl ether/N-isopropylacrylamide-grafted magnetic nanoparticles were prepared using silica-coated magnetic nanoparticles as a substrate for radical copolymerization of allyl glycidyl ether and N-isopropylacrylamide. Chitosan was coupled with the prepared nanoparticles by opening the epoxy ring of the allyl glycidyl ether. The thermosensitive magnetic nanocarrier (TSMNC) obtained can be applied as a potent drug carrier. The TSMNC structure was characterized using Fourier transform infrared spectroscopy, X-ray diffraction, thermogravimetric analysis, differential scanning calorimetry, vibrating sample magnetometer, and elemental analysis. Its morphology and size were investigated using field emission scanning electron microscopy, transmission electron microscopy and dynamic light scattering. The feasibility of employing the TSMNC for adsorption and in vitro controlled release of the chemotherapeutic agent sorafenib was tested. The effect of the adsorption parameters of pH, temperature, and loading time of sorafenib onto TSMNC was evaluated. The adsorption data was fitted to the Langmuir and Freundlich isotherms and the relevant parameters derived. The drug release profile indicated that 88% of the adsorbed drug was released within 35 h at 45 °C and drug release was Fickian diffusion-controlled. The results confirmed that the TSMNC has a high adsorption capacity at low temperature and good controlled release in a slow rate at a high temperature and could be developed for further application as a drug nanocarrier. - Graphical abstract: Magnetic nanoparticles were functionalized with chitosan and N-isopropylacrylamide. It was evaluated for sorafenib (SFB) adsorption and tested as a controlled-release system in response to changes in temperature. The TSMNC showed superparamagnetic properties with a high adsorption capacity and desirable controlled release at below and above LCST. Display Omitted - Highlights: • A TSMNC was synthesized for controlled

  18. Extremely stretchable thermosensitive hydrogels by introducing slide-ring polyrotaxane cross-linkers and ionic groups into the polymer network

    Science.gov (United States)

    Bin Imran, Abu; Esaki, Kenta; Gotoh, Hiroaki; Seki, Takahiro; Ito, Kohzo; Sakai, Yasuhiro; Takeoka, Yukikazu

    2014-01-01

    Stimuli-sensitive hydrogels changing their volumes and shapes in response to various stimulations have potential applications in multiple fields. However, these hydrogels have not yet been commercialized due to some problems that need to be overcome. One of the most significant problems is that conventional stimuli-sensitive hydrogels are usually brittle. Here we prepare extremely stretchable thermosensitive hydrogels with good toughness by using polyrotaxane derivatives composed of α-cyclodextrin and polyethylene glycol as cross-linkers and introducing ionic groups into the polymer network. The ionic groups help the polyrotaxane cross-linkers to become well extended in the polymer network. The resulting hydrogels are surprisingly stretchable and tough because the cross-linked α-cyclodextrin molecules can move along the polyethylene glycol chains. In addition, the polyrotaxane cross-linkers can be used with a variety of vinyl monomers; the mechanical properties of the wide variety of polymer gels can be improved by using these cross-linkers. PMID:25296246

  19. Single-cell axotomy of cultured hippocampal neurons integrated in neuronal circuits.

    Science.gov (United States)

    Gomis-Rüth, Susana; Stiess, Michael; Wierenga, Corette J; Meyn, Liane; Bradke, Frank

    2014-05-01

    An understanding of the molecular mechanisms of axon regeneration after injury is key for the development of potential therapies. Single-cell axotomy of dissociated neurons enables the study of the intrinsic regenerative capacities of injured axons. This protocol describes how to perform single-cell axotomy on dissociated hippocampal neurons containing synapses. Furthermore, to axotomize hippocampal neurons integrated in neuronal circuits, we describe how to set up coculture with a few fluorescently labeled neurons. This approach allows axotomy of single cells in a complex neuronal network and the observation of morphological and molecular changes during axon regeneration. Thus, single-cell axotomy of mature neurons is a valuable tool for gaining insights into cell intrinsic axon regeneration and the plasticity of neuronal polarity of mature neurons. Dissociation of the hippocampus and plating of hippocampal neurons takes ∼2 h. Neurons are then left to grow for 2 weeks, during which time they integrate into neuronal circuits. Subsequent axotomy takes 10 min per neuron and further imaging takes 10 min per neuron.

  20. Cold formability of steels

    International Nuclear Information System (INIS)

    Lafond, G.; Leclerq, G.; Moliexe, F.; Namdar, R.; Roesch, L.; Sanz, G.

    1977-01-01

    This work was essentially aimed to the study of the following three questions. Is it possible to assess the cold formability of steels using simple material properties as criteria. What values of mechanical properties can one expect to reach in cold formed parts. Are there simple ways of characterizing the speroidization treatments carried out on steels before cold forming operations. The present report describes the results obtained during this investigation. It is logically divided into three separate parts. Experimental study of cold formability in wire drawing. Influence of metallurgical variables on mechanical properties of high carbon cold drawn wires. Contribution to the study of characterization methods of cold forming steels subjected to a spheroidization heat treatment

  1. Human whole body cold adaptation.

    Science.gov (United States)

    Daanen, Hein A M; Van Marken Lichtenbelt, Wouter D

    2016-01-01

    Reviews on whole body human cold adaptation generally do not distinguish between population studies and dedicated acclimation studies, leading to confusing results. Population studies show that indigenous black Africans have reduced shivering thermogenesis in the cold and poor cold induced vasodilation in fingers and toes compared to Caucasians and Inuit. About 40,000 y after humans left Africa, natives in cold terrestrial areas seems to have developed not only behavioral adaptations, but also physiological adaptations to cold. Dedicated studies show that repeated whole body exposure of individual volunteers, mainly Caucasians, to severe cold results in reduced cold sensation but no major physiological changes. Repeated cold water immersion seems to slightly reduce metabolic heat production, while repeated exposure to milder cold conditions shows some increase in metabolic heat production, in particular non-shivering thermogenesis. In conclusion, human cold adaptation in the form of increased metabolism and insulation seems to have occurred during recent evolution in populations, but cannot be developed during a lifetime in cold conditions as encountered in temperate and arctic regions. Therefore, we mainly depend on our behavioral skills to live in and survive the cold.

  2. The impact of cold spells on mortality and effect modification by cold spell characteristics

    Science.gov (United States)

    Wang, Lijun; Liu, Tao; Hu, Mengjue; Zeng, Weilin; Zhang, Yonghui; Rutherford, Shannon; Lin, Hualiang; Xiao, Jianpeng; Yin, Peng; Liu, Jiangmei; Chu, Cordia; Tong, Shilu; Ma, Wenjun; Zhou, Maigeng

    2016-12-01

    In China, the health impact of cold weather has received little attention, which limits our understanding of the health impacts of climate change. We collected daily mortality and meteorological data in 66 communities across China from 2006 to 2011. Within each community, we estimated the effect of cold spell exposure on mortality using a Distributed Lag Nonlinear Model (DLNM). We also examined the modification effect of cold spell characteristics (intensity, duration, and timing) and individual-specific factors (causes of death, age, gender and education). Meta-analysis method was finally used to estimate the overall effects. The overall cumulative excess risk (CER) of non-accidental mortality during cold spell days was 28.2% (95% CI: 21.4%, 35.3%) compared with non-cold spell days. There was a significant increase in mortality when the cold spell duration and intensity increased or occurred earlier in the season. Cold spell effects and effect modification by cold spell characteristics were more pronounced in south China. The elderly, people with low education level and those with respiratory diseases were generally more vulnerable to cold spells. Cold spells statistically significantly increase mortality risk in China, with greater effects in southern China. This effect is modified by cold spell characteristics and individual-level factors.

  3. Neuronal survival in the brain: neuron type-specific mechanisms

    DEFF Research Database (Denmark)

    Pfisterer, Ulrich Gottfried; Khodosevich, Konstantin

    2017-01-01

    Neurogenic regions of mammalian brain produce many more neurons that will eventually survive and reach a mature stage. Developmental cell death affects both embryonically produced immature neurons and those immature neurons that are generated in regions of adult neurogenesis. Removal of substantial...... numbers of neurons that are not yet completely integrated into the local circuits helps to ensure that maturation and homeostatic function of neuronal networks in the brain proceed correctly. External signals from brain microenvironment together with intrinsic signaling pathways determine whether...... for survival in a certain brain region. This review focuses on how immature neurons survive during normal and impaired brain development, both in the embryonic/neonatal brain and in brain regions associated with adult neurogenesis, and emphasizes neuron type-specific mechanisms that help to survive for various...

  4. Identification, recombinant production and partial biochemical characterization of an extracellular cold-active serine-metalloprotease from an Antarctic Pseudomonas isolate

    Directory of Open Access Journals (Sweden)

    Natalia Fullana

    2017-08-01

    Full Text Available Cold-adapted enzymes are generally derived from psychrophilic microorganisms and have features that make them very attractive for industrial and biotechnological purposes. In this work, we identified a 50 kDa extracellular protease (MP10 from the Antarctic isolate Pseudomonas sp. AU10. The enzyme was produced by recombinant DNA technology, purified using immobilized metal affinity chromatography and partially characterized. MP10 is an alkaline thermosensitive serine-metallo protease with optimal activity at pH 8.0 and 40 ℃, in the presence of 1.5 mM Ca2+. MP10 showed 100% residual activity and stability (up to 60 min when incubated with 7% of non-ionic surfactants (Triton X-100, Tween-80 and Tween-20 and 1.5% of the oxidizing agent hydrogen peroxide. The 3D MP10 structure was predicted and compared with the crystal structure of mesophilic homologous protease produced by Pseudomonas aeruginosa PA01 (reference strain and other proteases, showing similarity in surface area and volume of proteins, but a significantly higher surface pocket area and volume of MP10. The observed differences presumably may explain the enhanced activity of MP10 for substrate binding at low temperatures. These results give insight to the potential use of MP10 in developing new biotechnologically processes active at low to moderate temperatures, probably with focus in the detergent industry.

  5. Origins, actions and dynamic expression patterns of the neuropeptide VGF in rat peripheral and central sensory neurones following peripheral nerve injury

    Directory of Open Access Journals (Sweden)

    Costigan Michael

    2008-12-01

    Full Text Available Abstract Background The role of the neurotrophin regulated polypeptide, VGF, has been investigated in a rat spared injury model of neuropathic pain. This peptide has been shown to be associated with synaptic strengthening and learning in the hippocampus and while it is known that VGFmRNA is upregulated in dorsal root ganglia following peripheral nerve injury, the role of this VGF peptide in neuropathic pain has yet to be investigated. Results Prolonged upregulation of VGF mRNA and protein was observed in injured dorsal root ganglion neurons, central terminals and their target dorsal horn neurons. Intrathecal application of TLQP-62, the C-terminal active portion of VGF (5–50 nmol to naïve rats caused a long-lasting mechanical and cold behavioral allodynia. Direct actions of 50 nM TLQP-62 upon dorsal horn neuron excitability was demonstrated in whole cell patch recordings in spinal cord slices and in receptive field analysis in intact, anesthetized rats where significant actions of VGF were upon spontaneous activity and cold evoked responses. Conclusion VGF expression is therefore highly modulated in nociceptive pathways following peripheral nerve injury and can cause dorsal horn cell excitation and behavioral hypersensitivity in naïve animals. Together the results point to a novel and powerful role for VGF in neuropathic pain.

  6. Parvalbumin+ Neurons and Npas1+ Neurons Are Distinct Neuron Classes in the Mouse External Globus Pallidus.

    Science.gov (United States)

    Hernández, Vivian M; Hegeman, Daniel J; Cui, Qiaoling; Kelver, Daniel A; Fiske, Michael P; Glajch, Kelly E; Pitt, Jason E; Huang, Tina Y; Justice, Nicholas J; Chan, C Savio

    2015-08-26

    Compelling evidence suggests that pathological activity of the external globus pallidus (GPe), a nucleus in the basal ganglia, contributes to the motor symptoms of a variety of movement disorders such as Parkinson's disease. Recent studies have challenged the idea that the GPe comprises a single, homogenous population of neurons that serves as a simple relay in the indirect pathway. However, we still lack a full understanding of the diversity of the neurons that make up the GPe. Specifically, a more precise classification scheme is needed to better describe the fundamental biology and function of different GPe neuron classes. To this end, we generated a novel multicistronic BAC (bacterial artificial chromosome) transgenic mouse line under the regulatory elements of the Npas1 gene. Using a combinatorial transgenic and immunohistochemical approach, we discovered that parvalbumin-expressing neurons and Npas1-expressing neurons in the GPe represent two nonoverlapping cell classes, amounting to 55% and 27% of the total GPe neuron population, respectively. These two genetically identified cell classes projected primarily to the subthalamic nucleus and to the striatum, respectively. Additionally, parvalbumin-expressing neurons and Npas1-expressing neurons were distinct in their autonomous and driven firing characteristics, their expression of intrinsic ion conductances, and their responsiveness to chronic 6-hydroxydopamine lesion. In summary, our data argue that parvalbumin-expressing neurons and Npas1-expressing neurons are two distinct functional classes of GPe neurons. This work revises our understanding of the GPe, and provides the foundation for future studies of its function and dysfunction. Until recently, the heterogeneity of the constituent neurons within the external globus pallidus (GPe) was not fully appreciated. We addressed this knowledge gap by discovering two principal GPe neuron classes, which were identified by their nonoverlapping expression of the

  7. Parvalbumin+ Neurons and Npas1+ Neurons Are Distinct Neuron Classes in the Mouse External Globus Pallidus

    Science.gov (United States)

    Hernández, Vivian M.; Hegeman, Daniel J.; Cui, Qiaoling; Kelver, Daniel A.; Fiske, Michael P.; Glajch, Kelly E.; Pitt, Jason E.; Huang, Tina Y.; Justice, Nicholas J.

    2015-01-01

    Compelling evidence suggests that pathological activity of the external globus pallidus (GPe), a nucleus in the basal ganglia, contributes to the motor symptoms of a variety of movement disorders such as Parkinson's disease. Recent studies have challenged the idea that the GPe comprises a single, homogenous population of neurons that serves as a simple relay in the indirect pathway. However, we still lack a full understanding of the diversity of the neurons that make up the GPe. Specifically, a more precise classification scheme is needed to better describe the fundamental biology and function of different GPe neuron classes. To this end, we generated a novel multicistronic BAC (bacterial artificial chromosome) transgenic mouse line under the regulatory elements of the Npas1 gene. Using a combinatorial transgenic and immunohistochemical approach, we discovered that parvalbumin-expressing neurons and Npas1-expressing neurons in the GPe represent two nonoverlapping cell classes, amounting to 55% and 27% of the total GPe neuron population, respectively. These two genetically identified cell classes projected primarily to the subthalamic nucleus and to the striatum, respectively. Additionally, parvalbumin-expressing neurons and Npas1-expressing neurons were distinct in their autonomous and driven firing characteristics, their expression of intrinsic ion conductances, and their responsiveness to chronic 6-hydroxydopamine lesion. In summary, our data argue that parvalbumin-expressing neurons and Npas1-expressing neurons are two distinct functional classes of GPe neurons. This work revises our understanding of the GPe, and provides the foundation for future studies of its function and dysfunction. SIGNIFICANCE STATEMENT Until recently, the heterogeneity of the constituent neurons within the external globus pallidus (GPe) was not fully appreciated. We addressed this knowledge gap by discovering two principal GPe neuron classes, which were identified by their nonoverlapping

  8. Humidity sensation requires both mechanosensory and thermosensory pathways in Caenorhabditis elegans.

    Science.gov (United States)

    Russell, Joshua; Vidal-Gadea, Andrés G; Makay, Alex; Lanam, Carolyn; Pierce-Shimomura, Jonathan T

    2014-06-03

    All terrestrial animals must find a proper level of moisture to ensure their health and survival. The cellular-molecular basis for sensing humidity is unknown in most animals, however. We used the model nematode Caenorhabditis elegans to uncover a mechanism for sensing humidity. We found that whereas C. elegans showed no obvious preference for humidity levels under standard culture conditions, worms displayed a strong preference after pairing starvation with different humidity levels, orienting to gradients as shallow as 0.03% relative humidity per millimeter. Cell-specific ablation and rescue experiments demonstrate that orientation to humidity in C. elegans requires the obligatory combination of distinct mechanosensitive and thermosensitive pathways. The mechanosensitive pathway requires a conserved DEG/ENaC/ASIC mechanoreceptor complex in the FLP neuron pair. Because humidity levels influence the hydration of the worm's cuticle, our results suggest that FLP may convey humidity information by reporting the degree that subcuticular dendritic sensory branches of FLP neurons are stretched by hydration. The thermosensitive pathway requires cGMP-gated channels in the AFD neuron pair. Because humidity levels affect evaporative cooling, AFD may convey humidity information by reporting thermal flux. Thus, humidity sensation arises as a metamodality in C. elegans that requires the integration of parallel mechanosensory and thermosensory pathways. This hygrosensation strategy, first proposed by Thunberg more than 100 y ago, may be conserved because the underlying pathways have cellular and molecular equivalents across a wide range of species, including insects and humans.

  9. Trench Foot or Non-Freezing Cold Injury As a Painful Vaso-Neuropathy: Clinical and Skin Biopsy Assessments

    Directory of Open Access Journals (Sweden)

    Praveen Anand

    2017-09-01

    Full Text Available BackgroundTrench foot, or non-freezing cold injury (NFCI, results from cold exposure of sufficient severity and duration above freezing point, with consequent sensory and vascular abnormalities which may persist for years. Based on observations of Trench foot in World War II, the condition was described as a vaso-neuropathy. While some reports have documented nerve damage after extreme cold exposure, sensory nerve fibres and vasculature have not been assessed with recent techniques in NFCI.ObjectiveTo assess patients with chronic sensory symptoms following cold exposure, in order to diagnose any underlying small fibre neuropathy, and provide insight into mechanisms of the persistent pain and cold hypersensitivity.MethodsThirty soldiers with cold exposure and persistent sensory symptoms (>4 months were assessed with quantitative sensory testing, nerve conduction studies, and skin biopsies. Immunohistochemistry was used to assess intraepidermal (IENF and subepidermal (SENF nerve fibres with a range of markers, including the pan-neuronal marker protein gene product 9.5 (PGP 9.5, regenerating fibres with growth-associated protein 43 (GAP43, and nociceptor fibres with transient receptor potential cation channel subfamily V member 1 (TRPV1, sensory neuron-specific receptor (SNSR, and calcitonin gene-related peptide (CGRP. von Willebrand factor (vWF, endothelial nitric oxide synthase (eNOS, and vascular endothelial growth factor (VEGF were used for assessing blood vessels, and transient receptor potential cation channel, subfamily A member 1 (TRPA1 and P2X purinoceptor 7 (P2X7 for keratinocytes, which regulate nociceptors via release of nerve growth factor.ResultsClinical examination showed pinprick sensation was abnormal in the feet of 20 patients (67%, and between 67 and 83% had abnormalities of thermal thresholds to the different modalities. 7 patients (23% showed reduced sensory action potential amplitude of plantar nerves. 27 patients (90% had

  10. Cold/menthol TRPM8 receptors initiate the cold-shock response and protect germ cells from cold-shock-induced oxidation.

    Science.gov (United States)

    Borowiec, Anne-Sophie; Sion, Benoit; Chalmel, Frédéric; D Rolland, Antoine; Lemonnier, Loïc; De Clerck, Tatiana; Bokhobza, Alexandre; Derouiche, Sandra; Dewailly, Etienne; Slomianny, Christian; Mauduit, Claire; Benahmed, Mohamed; Roudbaraki, Morad; Jégou, Bernard; Prevarskaya, Natalia; Bidaux, Gabriel

    2016-09-01

    Testes of most male mammals present the particularity of being externalized from the body and are consequently slightly cooler than core body temperature (4-8°C below). Although, hypothermia of the testis is known to increase germ cells apoptosis, little is known about the underlying molecular mechanisms, including cold sensors, transduction pathways, and apoptosis triggers. In this study, using a functional knockout mouse model of the cold and menthol receptors, dubbed transient receptor potential melastatine 8 (TRPM8) channels, we found that TRPM8 initiated the cold-shock response by differentially modulating cold- and heat-shock proteins. Besides, apoptosis of germ cells increased in proportion to the cooling level in control mice but was independent of temperature in knockout mice. We also observed that the rate of germ cell death correlated positively with the reactive oxygen species level and negatively with the expression of the detoxifying enzymes. This result suggests that the TRPM8 sensor is a key determinant of germ cell fate under hypothermic stimulation.-Borowiec, A.-S., Sion, B., Chalmel, F., Rolland, A. D., Lemonnier, L., De Clerck, T., Bokhobza, A., Derouiche, S., Dewailly, E., Slomianny, C., Mauduit, C., Benahmed, M., Roudbaraki, M., Jégou, B., Prevarskaya, N., Bidaux, G. Cold/menthol TRPM8 receptors initiate the cold-shock response and protect germ cells from cold-shock-induced oxidation. © The Author(s).

  11. Coherence resonance in globally coupled neuronal networks with different neuron numbers

    International Nuclear Information System (INIS)

    Ning Wei-Lian; Zhang Zheng-Zhen; Zeng Shang-You; Luo Xiao-Shu; Hu Jin-Lin; Zeng Shao-Wen; Qiu Yi; Wu Hui-Si

    2012-01-01

    Because a brain consists of tremendous neuronal networks with different neuron numbers ranging from tens to tens of thousands, we study the coherence resonance due to ion channel noises in globally coupled neuronal networks with different neuron numbers. We confirm that for all neuronal networks with different neuron numbers there exist the array enhanced coherence resonance and the optimal synaptic conductance to cause the maximal spiking coherence. Furthermoremore, the enhancement effects of coupling on spiking coherence and on optimal synaptic conductance are almost the same, regardless of the neuron numbers in the neuronal networks. Therefore for all the neuronal networks with different neuron numbers in the brain, relative weak synaptic conductance (0.1 mS/cm 2 ) is sufficient to induce the maximal spiking coherence and the best sub-threshold signal encoding. (interdisciplinary physics and related areas of science and technology)

  12. Neuroprotection via RNA-binding protein RBM3 expression is regulated by hypothermia but not by hypoxia in human SK-N-SH neurons

    Directory of Open Access Journals (Sweden)

    Rosenthal LM

    2017-05-01

    Full Text Available Lisa-Maria Rosenthal,1 Giang Tong,1 Christoph Walker,1 Sylvia J Wowro,1 Jana Krech,1 Constanze Pfitzer,1,2 Georgia Justus,1 Felix Berger,1,3 Katharina Rose Luise Schmitt1 1Department of Congenital Heart Disease/Pediatric Cardiology, German Heart Institute Berlin, 2Berlin Institute of Health (BIH, 3Department of Pediatric Cardiology, Charité – University Medical Center, Berlin, Germany Objective: Therapeutic hypothermia is an established treatment for perinatal asphyxia. Yet, many term infants continue to die or suffer from neurodevelopmental disability. Several experimental studies have demonstrated a beneficial effect of mild-to-moderate hypothermia after hypoxic injury, but the understanding of hypothermia-induced neuroprotection remains incomplete. In general, global protein synthesis is attenuated by hypothermia, but a small group of RNA-binding proteins including the RNA-binding motif 3 (RBM3 is upregulated in response to cooling. The aim of this study was to establish an in vitro model to investigate the effects of hypoxia and hypothermia on neuronal cell survival, as well as to examine the kinetics of concurrent cold-shock protein RBM3 gene expression. Methods: Experiments were performed by using human SK-N-SH neurons exposed to different oxygen concentrations (21%, 8%, or 0.2% O2 for 24 hours followed by moderate hypothermia (33.5°C or normothermia for 24, 48, or 72 hours. Cell death was determined by quantification of lactate dehydrogenase and neuron-specific enolase releases into the cell cultured medium, and cell morphology was assessed by using immunofluorescence staining. The regulation of RBM3 gene expression was assessed by reverse transcriptase-quantitative polymerase chain reaction and Western blot analysis.Results: Exposure to hypoxia (0.2% O2 for 24 hours resulted in significantly increased cell death in SK-N-SH neurons, whereas exposure to 8% O2 had no significant impact on cell viability. Post-hypoxia treatment with

  13. [Effects of ingredients from Chinese herbs with nature of cold or hot on expression of TRPV1 and TRPM8].

    Science.gov (United States)

    Sui, Feng; Yang, Na; Zhang, Changbin; Du, Xinliang; Li, Lanfang; Weng, Xiaogang; Guo, Shuying; Huo, Hairu; Jiang, Tingliang

    2010-06-01

    To study the effects of the ingredients from Chinese herbs with the nature of cold or hot on the expression of TRPV1 and TRPM8. The effects of ingredients from herbs on primary culture DRG neurons are observed in vitro. The expression quantity of gene is detected by the method of real time PCR. the 2 (-deltadeltaCT) method is applied to analyze the data. Ingredients from herbs with the nature of cold up-regulate the expression level of TRPV1 and down-regulate that of TRPM8, especially under the temperature condition of 39 degrees C; while ingredients from herbs with the nature of hot up-regulate the expression level of TRPM8 and down-regulated that of TRPV1, which is more significant under the temperature condition of 19 degrees C. The regulatory changes of TRPV1 and TRPM8 mRNA expression induced by the chemical ingredients might be related to the cold and hot natures of the herbs from which the ingredients are extracted. And this could be one of the therapeutic mechanisms for the treatment of Chinese herbal medicines to cold- and heat-related diseases.

  14. Cold stress alters transcription in meiotic anthers of cold tolerant chickpea (Cicer arietinum L.).

    Science.gov (United States)

    Sharma, Kamal Dev; Nayyar, Harsh

    2014-10-11

    Cold stress at reproductive phase in susceptible chickpea (Cicer arietinum L.) leads to pollen sterility induced flower abortion. The tolerant genotypes, on the other hand, produce viable pollen and set seed under cold stress. Genomic information on pollen development in cold-tolerant chickpea under cold stress is currently unavailable. DDRT-PCR analysis was carried out to identify anther genes involved in cold tolerance in chickpea genotype ICC16349 (cold-tolerant). A total of 9205 EST bands were analyzed. Cold stress altered expression of 127 ESTs (90 up-regulated, 37 down-regulated) in anthers, more than two third (92) of which were novel with unknown protein identity and function. Remaining about one third (35) belonged to several functional categories such as pollen development, signal transduction, ion transport, transcription, carbohydrate metabolism, translation, energy and cell division. The categories with more number of transcripts were carbohydrate/triacylglycerol metabolism, signal transduction, pollen development and transport. All but two transcripts in these categories were up-regulated under cold stress. To identify time of regulation after stress and organ specificity, expression levels of 25 differentially regulated transcripts were also studied in anthers at six time points and in four organs (anthers, gynoecium, leaves and roots) at four time points. Limited number of genes were involved in regulating cold tolerance in chickpea anthers. Moreover, the cold tolerance was manifested by up-regulation of majority of the differentially expressed transcripts. The anthers appeared to employ dual cold tolerance mechanism based on their protection from cold by enhancing triacylglycerol and carbohydrate metabolism; and maintenance of normal pollen development by regulating pollen development genes. Functional characterization of about two third of the novel genes is needed to have precise understanding of the cold tolerance mechanisms in chickpea anthers.

  15. Cough & Cold Medicine Abuse

    Science.gov (United States)

    ... Videos for Educators Search English Español Cough & Cold Medicine Abuse KidsHealth / For Teens / Cough & Cold Medicine Abuse ... resfriado Why Do People Use Cough and Cold Medicines to Get High? There's an ingredient in many ...

  16. Neuron-derived IgG protects neurons from complement-dependent cytotoxicity.

    Science.gov (United States)

    Zhang, Jie; Niu, Na; Li, Bingjie; McNutt, Michael A

    2013-12-01

    Passive immunity of the nervous system has traditionally been thought to be predominantly due to the blood-brain barrier. This concept must now be revisited based on the existence of neuron-derived IgG. The conventional concept is that IgG is produced solely by mature B lymphocytes, but it has now been found to be synthesized by murine and human neurons. However, the function of this endogenous IgG is poorly understood. In this study, we confirm IgG production by rat cortical neurons at the protein and mRNA levels, with 69.0 ± 5.8% of cortical neurons IgG-positive. Injury to primary-culture neurons was induced by complement leading to increases in IgG production. Blockage of neuron-derived IgG resulted in more neuronal death and early apoptosis in the presence of complement. In addition, FcγRI was found in microglia and astrocytes. Expression of FcγR I in microglia was increased by exposure to neuron-derived IgG. Release of NO from microglia triggered by complement was attenuated by neuron-derived IgG, and this attenuation could be reversed by IgG neutralization. These data demonstrate that neuron-derived IgG is protective of neurons against injury induced by complement and microglial activation. IgG appears to play an important role in maintaining the stability of the nervous system.

  17. A neuron-astrocyte transistor-like model for neuromorphic dressed neurons.

    Science.gov (United States)

    Valenza, G; Pioggia, G; Armato, A; Ferro, M; Scilingo, E P; De Rossi, D

    2011-09-01

    Experimental evidences on the role of the synaptic glia as an active partner together with the bold synapse in neuronal signaling and dynamics of neural tissue strongly suggest to investigate on a more realistic neuron-glia model for better understanding human brain processing. Among the glial cells, the astrocytes play a crucial role in the tripartite synapsis, i.e. the dressed neuron. A well-known two-way astrocyte-neuron interaction can be found in the literature, completely revising the purely supportive role for the glia. The aim of this study is to provide a computationally efficient model for neuron-glia interaction. The neuron-glia interactions were simulated by implementing the Li-Rinzel model for an astrocyte and the Izhikevich model for a neuron. Assuming the dressed neuron dynamics similar to the nonlinear input-output characteristics of a bipolar junction transistor, we derived our computationally efficient model. This model may represent the fundamental computational unit for the development of real-time artificial neuron-glia networks opening new perspectives in pattern recognition systems and in brain neurophysiology. Copyright © 2011 Elsevier Ltd. All rights reserved.

  18. Effect of salt on a thermosensitive mutant of Bacillus subtilis deficient in uracil and cell division

    Energy Technology Data Exchange (ETDEWEB)

    Miyazaki, N; Nagai, K; Tamura, G

    1976-01-01

    A thermosensitive uracil requiring mutant of Bacillus subtilis Marburg 168 thy trp/sub 2/ ts42 was examined as to the colony forming ability at the permissive and nonpermissive temperatures. The viability of the mutant cells decreased rapidly at the restrictive temperature in the modified Woese's (MW) medium. However, the cells retained viability when sodium succinate or potassium chloride was added to the medium at that temperature although uracil deficiency was unchanged. A little but significant incorporation of adenine-8-/sup 14/C into RNA still continued even after the incorporation of N-acetyl-/sup 3/H-D-glucosamine into acid insoluble fraction of the cells terminated in the MW medium at 48/sup 0/C. Both incorporations as well as increase of absorbance were slowed down in the presence of sodium succinate at 48/sup 0/C. This mutant, ts-42, was more sensitive to deoxycholate (DOC) than the parent strain. The restoration of colony forming ability after the temperature shift back to 37/sup 0/C was suppressed by the addition of DOC to the medium. However, the cell became resistant to DOC when uracil was added to the medium prior to the temperature shift.

  19. Radiation grafting of pH and thermosensitive N-isopropylacrylamide and acrylic acid onto PTFE films by two-steps process

    International Nuclear Information System (INIS)

    Bucio, E.; Burillo, G.

    2007-01-01

    Polytetrafluoroethylene (PTFE) was grafted (g) with acrylic acid (AAc) by γ-ray pre-irradiation method to get PTFE-g-AAc films, then N-isopropylacrylamide (NIPAAm) was grafted onto PTFE-g-AAc films with γ-ray to get (PTFE-g-AAc)-g-NIPAAm. PTFE films were irradiated in air at a dose rate of 3.0 kGy h -1 and different radiation dose. The irradiated films were placed in glass ampoules, which contained aqueous solutions with different monomer concentration (AAc), and then they were heated at different temperatures and reaction time. NIPAAm onto PTFE-g-AAc was carried out with the same procedure with monomer concentration of 1 mol L -1 . The thermosensitivity of the samples was defined and calculated as the ratio of the grafted samples swelling at 28 and 35 o C, and pH sensitivity defined as the ratio of the grafted samples swelling at pH 2 and 8

  20. Adsorption and Desorption of Na+ and NO3− Ions on Thermosensitive NIPAM-co-DMAAPS Gel in Aqueous Solution

    Directory of Open Access Journals (Sweden)

    Eva Oktavia Ningrum

    2017-11-01

    Full Text Available Adsorbent gel with the ability to absorb and to desorb Na+ and NO3− ions simultaneously with temperature swing was synthesized by free radical copolymerization reaction of N-isopropylacrylamide (NIPAM and N,N-dimethyl-(acrylamidopropylammonium propane sulfonate (DMAAPS. In this study, NIPAM acts as a thermosensitive agent and DMAAPS as an adsorbent agent. The purpose of this research is to investigate the effect of temperature and solution concentration on the swelling, adsorption, and desorption behaviors of NIPAM-co-DMAAPS gel. The relationship between adsorption and desorption behaviors of the gel was also elucidated. NaNO3 solution was selected as the target solution in swelling, adsorption, and desorption test. It was observed that the swelling degree of the gel increased as temperature and solution concentration raised. The adsorption amount of ions decreased with the increase of temperature. In contrast, the amount of ions desorbed from the gel increased linearly with temperature.

  1. Inhibitory neurons modulate spontaneous signaling in cultured cortical neurons: density-dependent regulation of excitatory neuronal signaling

    International Nuclear Information System (INIS)

    Serra, Michael; Guaraldi, Mary; Shea, Thomas B

    2010-01-01

    Cortical neuronal activity depends on a balance between excitatory and inhibitory influences. Culturing of neurons on multi-electrode arrays (MEAs) has provided insight into the development and maintenance of neuronal networks. Herein, we seeded MEAs with murine embryonic cortical/hippocampal neurons at different densities ( 1000 cells mm −2 ) and monitored resultant spontaneous signaling. Sparsely seeded cultures displayed a large number of bipolar, rapid, high-amplitude individual signals with no apparent temporal regularity. By contrast, densely seeded cultures instead displayed clusters of signals at regular intervals. These patterns were observed even within thinner and thicker areas of the same culture. GABAergic neurons (25% of total neurons in our cultures) mediated the differential signal patterns observed above, since addition of the inhibitory antagonist bicuculline to dense cultures and hippocampal slice cultures induced the signal pattern characteristic of sparse cultures. Sparsely seeded cultures likely lacked sufficient inhibitory neurons to modulate excitatory activity. Differential seeding of MEAs can provide a unique model for analyses of pertubation in the interaction between excitatory and inhibitory function during aging and neuropathological conditions where dysregulation of GABAergic neurons is a significant component

  2. Estimation of the Void Fraction in the moderator cell of the Cold Neutron Source

    Energy Technology Data Exchange (ETDEWEB)

    Choi, Jungwoon; Kim, Young-ki [Korea Atomic Energy Research Institute, Daejeon (Korea, Republic of)

    2015-10-15

    To estimate the average void fraction in the liquid hydrogen, the Kazimi and Chen correlation is used with its modified method suggested by R.E. Williams in NBSR. Since the multiplying number can be changed along the operation condition and working fluid, the different figure is applied to estimate the average void fraction in the different moderator cell shape. This approach is checked with the void fraction measurement results from the HANARO-CNS mock-up test. Owing to national research demands on cold neutron beam utilization, the Cold Neutron Research Facility had been and operated for neuron scientists all over the world. In HANARO, the CNS facility has been operated since 2009. The actual void fraction, which is the one of dominant factors affecting the cold neutron flux, is difficult to know without the real measurement performed at the cryogenic temperature using the same moderator medium. Accordingly, the two-phase mock-up test in the CNS-IPA (In-pool assembly) had been performed using the liquid hydrogen in terms of the fluidity check, void fraction measurement, operation procedure set-up, and so on for the development of the HANARO-CNS. This paper presents the estimated void fraction in the different operating conditions and geometrical shape in the comparison with the measurement data of the void fraction in the full-scale mockup test based on the Kazimi and Chen correlation. This approach is applied to estimate the average void fraction in the newly designed moderator cell using the liquid hydrogen as a working fluid in the two-phase thermosiphon. From this calculation result, the estimated average void fraction will be used to design the optimized cold neutron source to produce the maximum cold neutron flux within the desired wavelength.

  3. Estimation of the Void Fraction in the moderator cell of the Cold Neutron Source

    International Nuclear Information System (INIS)

    Choi, Jungwoon; Kim, Young-ki

    2015-01-01

    To estimate the average void fraction in the liquid hydrogen, the Kazimi and Chen correlation is used with its modified method suggested by R.E. Williams in NBSR. Since the multiplying number can be changed along the operation condition and working fluid, the different figure is applied to estimate the average void fraction in the different moderator cell shape. This approach is checked with the void fraction measurement results from the HANARO-CNS mock-up test. Owing to national research demands on cold neutron beam utilization, the Cold Neutron Research Facility had been and operated for neuron scientists all over the world. In HANARO, the CNS facility has been operated since 2009. The actual void fraction, which is the one of dominant factors affecting the cold neutron flux, is difficult to know without the real measurement performed at the cryogenic temperature using the same moderator medium. Accordingly, the two-phase mock-up test in the CNS-IPA (In-pool assembly) had been performed using the liquid hydrogen in terms of the fluidity check, void fraction measurement, operation procedure set-up, and so on for the development of the HANARO-CNS. This paper presents the estimated void fraction in the different operating conditions and geometrical shape in the comparison with the measurement data of the void fraction in the full-scale mockup test based on the Kazimi and Chen correlation. This approach is applied to estimate the average void fraction in the newly designed moderator cell using the liquid hydrogen as a working fluid in the two-phase thermosiphon. From this calculation result, the estimated average void fraction will be used to design the optimized cold neutron source to produce the maximum cold neutron flux within the desired wavelength

  4. Thermosensitive hydrogel based on chitosan and its derivatives containing medicated nanoparticles for transcorneal administration of 5-fluorouracil

    Directory of Open Access Journals (Sweden)

    Fabiano A

    2017-01-01

    Full Text Available Angela Fabiano,1 Ranieri Bizzarri,2 Ylenia Zambito1 1Department of Pharmacy, University of Pisa, 2NEST, Istituto Nanoscienze CNR (CNR-NANO and Scuola Normale Superiore, Pisa, Italy Abstract: A thermosensitive ophthalmic hydrogel (TSOH – fluid at 4°C (instillation temperature, semisolid at 35°C (eye temperature, which coupled the dosing accuracy and administration ease of eyedrops with the increased ocular bioavailability of a hydrogel – was prepared by gelling a chitosan hydrochloride (ChHCl solution (27.8 mg/mL medicated with 1.25 mg/mL 5-fluorouracil (5-FU with β-glycerophosphate 0.8 mg/mL. Polymer mixtures, where Ch was partially (10%, 15%, or 20% replaced by quaternary ammonium–chitosan conjugates (QA-Ch or thiolated derivatives thereof, were also used to modulate 5-FU-release properties of TSOH. Also, Ch-based nanoparticles (NPs; size after lyophilization and redispersion 341.5±15.2 nm, polydispersity 0.315±0.45, ζ-potential 10.21 mV medicated with 1.25 mg/mL 5-FU prepared by ionotropic cross-linking of Ch with hyaluronan were introduced into TSOH. The 5-FU binding by TSOH polymers in the sol state was maximum with plain Ch (31.4% and tended to decrease with increasing QA presence in polymer mixture. 5-FU release from TSOH with or without NPs was diffusion-controlled and linear in √t. The different TSOH polymers were compared on a diffusivity basis by comparing the slopes of √t plots. These showed a general decrease with NP-containing TSOH, which was the most marked with the TSOH, where Ch was 20% replaced by the derivative QA-Ch50. This formulation and that not containing NP were instilled in rabbits and the 5-FU transcorneal penetration was measured by analyzing the aqueous humor. Both TSOH solutions increased the area under the curve (0–8 hours 3.5 times compared with the plain eyedrops, but maximum concentration for the NP-free TSOH was about 0.65 µg/mL, followed by a slow decline, while the NP-containing one showed a

  5. Sustained Release of Protein Therapeutics from Subcutaneous Thermosensitive Biocompatible and Biodegradable Pentablock Copolymers (PTSgels

    Directory of Open Access Journals (Sweden)

    Elizabeth Schaefer

    2016-01-01

    Full Text Available Objective. To evaluate thermosensitive, biodegradable pentablock copolymers (PTSgel for sustained release and integrity of a therapeutic protein when injected subcutaneously. Materials and Methods. Five PTSgels with PEG-PCL-PLA-PCL-PEG block arrangements were synthesized. In vitro release of IgG from PTSgels and concentrations was evaluated at 37°C. Released IgG integrity was characterized by SDS-PAGE. In vitro disintegration for 10GH PTSgel in PBS was monitored at 37°C over 72 days using gravimetric loss and GPC analysis. Near-infrared IgG in PTSgel was injected subcutaneously and examined by in vivo imaging and histopathology for up to 42 days. Results. IgG release was modulated from approximately 7 days to more than 63 days in both in vitro and in vivo testing by varying polymer composition, concentration of PTSgel aqueous solution, and concentration of IgG. Released IgG in vitro maintained structural integrity by SDS-PAGE. Subcutaneous PTSgels were highly biocompatible and in vitro IgG release occurred in parallel with the disappearance of subcutaneous gel in vivo. Conclusions. Modulation of release of biologics to fit the therapeutic need can be achieved by varying the biocompatible and biodegradable PTSgel composition. Release of IgG parallels disappearance of the polymeric gel; hence, little or no PTSgel remains after drug release is complete.

  6. Enhanced mechanical properties of thermosensitive chitosan hydrogel by silk fibers for cartilage tissue engineering.

    Science.gov (United States)

    Mirahmadi, Fereshteh; Tafazzoli-Shadpour, Mohammad; Shokrgozar, Mohammad Ali; Bonakdar, Shahin

    2013-12-01

    Articular cartilage has limited repair capability following traumatic injuries and current methods of treatment remain inefficient. Reconstructing cartilage provides a new way for cartilage repair and natural polymers are often used as scaffold because of their biocompatibility and biofunctionality. In this study, we added degummed chopped silk fibers and electrospun silk fibers to the thermosensitive chitosan/glycerophosphate hydrogels to reinforce two hydrogel constructs which were used as scaffold for hyaline cartilage regeneration. The gelation temperature and gelation time of hydrogel were analyzed by the rheometer and vial tilting method. Mechanical characterization was measured by uniaxial compression, indentation and dynamic mechanical analysis assay. Chondrocytes were then harvested from the knee joint of the New Zealand white rabbits and cultured in constructs. The cell proliferation, viability, production of glycosaminoglycans and collagen type II were assessed. The results showed that mechanical properties of the hydrogel were significantly enhanced when a hybrid with two layers of electrospun silk fibers was made. The results of GAG and collagen type II in cell-seeded scaffolds indicate support of the chondrogenic phenotype for chondrocytes with a significant increase in degummed silk fiber-hydrogel composite for GAG content and in two-layer electrospun fiber-hydrogel composite for Col II. It was concluded that these two modified scaffolds could be employed for cartilage tissue engineering. © 2013.

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

    Science.gov (United States)

    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 (pneurons 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 dendrites. These neurons are

  8. Commemoration of a cold war

    DEFF Research Database (Denmark)

    Farbøl, Rosanna

    2015-01-01

    This article brings together the fields of Cold War studies and memory studies. In Denmark, a remarkable institutionalisation of Cold War memory has taken place in the midst of a heated ideological battle over the past and whether to remember the Cold War as a ‘war’. Using Danish Cold War museums...... and heritage sites as case studies, this article sheds new light on the politics of history involved in Cold War commemoration. It suggests that the Cold War is commemorated as a war, yet this war memory is of a particular kind: it is a war memory without victims....

  9. Cold thermal injury from cold caps used for the prevention of chemotherapy-induced alopecia.

    Science.gov (United States)

    Belum, Viswanath Reddy; de Barros Silva, Giselle; Laloni, Mariana Tosello; Ciccolini, Kathryn; Goldfarb, Shari B; Norton, Larry; Sklarin, Nancy T; Lacouture, Mario E

    2016-06-01

    The use of scalp cooling for the prevention of chemotherapy-induced alopecia (CIA) is increasing. Cold caps are placed onto the hair-bearing areas of the scalp for varying time periods before, during, and after cytotoxic chemotherapy. Although not yet reported, improper application procedures could result in adverse events (AEs). At present, there are no evidence-based scalp cooling protocols, and there is no regulatory oversight of their use. To report the occurrence of cold thermal injury (frostbite) on the scalp, following the use of cold caps for the prevention of CIA. We identified four patients who developed cold thermal injuries on the scalp following the application of cold caps. Medical records were analyzed to retrieve the demographic and clinical characteristics. The cold thermal injuries in our patients were grade 1/2 in severity and improved with topical interventions and interruption of cold cap use, although grade 1 persistent alopecia ensued in 3 patients. The true incidence of such injuries in this setting, however, remains unknown. Cold thermal injuries are likely infrequent and preventable AEs that may result from improper device application procedures during cold cap use. Although these untoward events are usually mild to moderate in severity, the potential occurrence of long-term sequelae (e.g., permanent alopecia and scarring) or the need to discontinue cold cap use, are not known. Prospective studies are needed to further elucidate the risk and standardize healthcare delivery methods, and to improve patient/supportive/healthcare provider education.

  10. Neuronal Migration and Neuronal Migration Disorder in Cerebral Cortex

    OpenAIRE

    SUN, Xue-Zhi; TAKAHASHI, Sentaro; GUI, Chun; ZHANG, Rui; KOGA, Kazuo; NOUYE, Minoru; MURATA, Yoshiharu

    2002-01-01

    Neuronal cell migration is one of the most significant features during cortical development. After final mitosis, neurons migrate from the ventricular zone into the cortical plate, and then establish neuronal lamina and settle onto the outermost layer, forming an "inside-out" gradient of maturation. Neuronal migration is guided by radial glial fibers and also needs proper receptors, ligands, and other unknown extracellular factors, requests local signaling (e.g. some emitted by the Cajal-Retz...

  11. Contribution of synchronized GABAergic neurons to dopaminergic neuron firing and bursting.

    Science.gov (United States)

    Morozova, Ekaterina O; Myroshnychenko, Maxym; Zakharov, Denis; di Volo, Matteo; Gutkin, Boris; Lapish, Christopher C; Kuznetsov, Alexey

    2016-10-01

    In the ventral tegmental area (VTA), interactions between dopamine (DA) and γ-aminobutyric acid (GABA) neurons are critical for regulating DA neuron activity and thus DA efflux. To provide a mechanistic explanation of how GABA neurons influence DA neuron firing, we developed a circuit model of the VTA. The model is based on feed-forward inhibition and recreates canonical features of the VTA neurons. Simulations revealed that γ-aminobutyric acid (GABA) receptor (GABAR) stimulation can differentially influence the firing pattern of the DA neuron, depending on the level of synchronization among GABA neurons. Asynchronous activity of GABA neurons provides a constant level of inhibition to the DA neuron and, when removed, produces a classical disinhibition burst. In contrast, when GABA neurons are synchronized by common synaptic input, their influence evokes additional spikes in the DA neuron, resulting in increased measures of firing and bursting. Distinct from previous mechanisms, the increases were not based on lowered firing rate of the GABA neurons or weaker hyperpolarization by the GABAR synaptic current. This phenomenon was induced by GABA-mediated hyperpolarization of the DA neuron that leads to decreases in intracellular calcium (Ca 2+ ) concentration, thus reducing the Ca 2+ -dependent potassium (K + ) current. In this way, the GABA-mediated hyperpolarization replaces Ca 2+ -dependent K + current; however, this inhibition is pulsatile, which allows the DA neuron to fire during the rhythmic pauses in inhibition. Our results emphasize the importance of inhibition in the VTA, which has been discussed in many studies, and suggest a novel mechanism whereby computations can occur locally. Copyright © 2016 the American Physiological Society.

  12. Hindbrain Catecholamine Neurons Activate Orexin Neurons During Systemic Glucoprivation in Male Rats.

    Science.gov (United States)

    Li, Ai-Jun; Wang, Qing; Elsarelli, Megan M; Brown, R Lane; Ritter, Sue

    2015-08-01

    Hindbrain catecholamine neurons are required for elicitation of feeding responses to glucose deficit, but the forebrain circuitry required for these responses is incompletely understood. Here we examined interactions of catecholamine and orexin neurons in eliciting glucoprivic feeding. Orexin neurons, located in the perifornical lateral hypothalamus (PeFLH), are heavily innervated by hindbrain catecholamine neurons, stimulate food intake, and increase arousal and behavioral activation. Orexin neurons may therefore contribute importantly to appetitive responses, such as food seeking, during glucoprivation. Retrograde tracing results showed that nearly all innervation of the PeFLH from the hindbrain originated from catecholamine neurons and some raphe nuclei. Results also suggested that many catecholamine neurons project collaterally to the PeFLH and paraventricular hypothalamic nucleus. Systemic administration of the antiglycolytic agent, 2-deoxy-D-glucose, increased food intake and c-Fos expression in orexin neurons. Both responses were eliminated by a lesion of catecholamine neurons innervating orexin neurons using the retrogradely transported immunotoxin, anti-dopamine-β-hydroxylase saporin, which is specifically internalized by dopamine-β-hydroxylase-expressing catecholamine neurons. Using designer receptors exclusively activated by designer drugs in transgenic rats expressing Cre recombinase under the control of tyrosine hydroxylase promoter, catecholamine neurons in cell groups A1 and C1 of the ventrolateral medulla were activated selectively by peripheral injection of clozapine-N-oxide. Clozapine-N-oxide injection increased food intake and c-Fos expression in PeFLH orexin neurons as well as in paraventricular hypothalamic nucleus neurons. In summary, catecholamine neurons are required for the activation of orexin neurons during glucoprivation. Activation of orexin neurons may contribute to appetitive responses required for glucoprivic feeding.

  13. Fluid mechanics in dentinal microtubules provides mechanistic insights into the difference between hot and cold dental pain.

    Science.gov (United States)

    Lin, Min; Luo, Zheng Yuan; Bai, Bo Feng; Xu, Feng; Lu, Tian Jian

    2011-03-23

    Dental thermal pain is a significant health problem in daily life and dentistry. There is a long-standing question regarding the phenomenon that cold stimulation evokes sharper and more shooting pain sensations than hot stimulation. This phenomenon, however, outlives the well-known hydrodynamic theory used to explain dental thermal pain mechanism. Here, we present a mathematical model based on the hypothesis that hot or cold stimulation-induced different directions of dentinal fluid flow and the corresponding odontoblast movements in dentinal microtubules contribute to different dental pain responses. We coupled a computational fluid dynamics model, describing the fluid mechanics in dentinal microtubules, with a modified Hodgkin-Huxley model, describing the discharge behavior of intradental neuron. The simulated results agreed well with existing experimental measurements. We thence demonstrated theoretically that intradental mechano-sensitive nociceptors are not "equally sensitive" to inward (into the pulp) and outward (away from the pulp) fluid flows, providing mechanistic insights into the difference between hot and cold dental pain. The model developed here could enable better diagnosis in endodontics which requires an understanding of pulpal histology, neurology and physiology, as well as their dynamic response to the thermal stimulation used in dental practices.

  14. The Jeremiah Metzger Lecture. The pathogenesis of fever in human subjects.

    OpenAIRE

    Wolff, S. M.; Dinarello, C. A.

    1980-01-01

    The pathogenesis of fever in man begins with the production of endogenous pyrogen by phagocytic leukocytes in response to exogenous pyrogens (toxic, immunologic or infectious agents). Endogenous pyrogen, a protein, is released from a variety of phagocytic leukocytes and enters the circulation after new messenger RNA and protein are synthesized. Fever is caused by an interaction of endogenous pyrogen with specialized receptors on or near thermosensitive neurons in the thermoregulatory center o...

  15. Cold urticaria: inhibition of cold-induced histamine release by doxantrazole.

    Science.gov (United States)

    Bentley-Phillips, C B; Eady, R A; Greaves, M W

    1978-10-01

    Thirteen patients with cold urticaria were studied to assess the effect of the systemic drug doxantrazole, which has actions resembling disodium cromoglycate, on cold evoked histamine release. The patients, all of whom developed an immediate local whealing response after cooling of the forearm, demonstrated release of histamine into venous blood draining that forearm. Following doxantrazole treatment, significant suppression of histamine release occurred. In some but not all patients this was accompanied by diminution of urtication in response to cooling. A double-blind study was carried out in 3 subjects, all of whom showed diminished cold-stimulated histamine release after doxantrazole. Two of these showed clinical improvement. Doxantrazole had no effect on erythema due to intradermal histamine, but did suppress the erythematous reaction to intradermal injection of compound 48/80. Our results suggest that doxantrazole or related anti-allergic agents might be useful in the treatment of cold urticaria.

  16. 77 FR 43117 - Meeting of the Cold War Advisory Committee for the Cold War Theme Study

    Science.gov (United States)

    2012-07-23

    ... the Cold War Advisory Committee for the Cold War Theme Study AGENCY: National Park Service, Interior... Committee Act, 5 U.S.C. Appendix, that the Cold War Advisory Committee for the Cold War Theme Study will... National Park Service (NPS) concerning the Cold War Theme Study. DATES: The teleconference meeting will be...

  17. Development of Cold Neutron Activation Station at HANARO Cold Neutron Source

    International Nuclear Information System (INIS)

    Sun, G. M.; Hoang, S. M. T.; Moon, J. H.; Chung, Y. S.; Cho, S. J.; Lee, K. H.; Park, B. G.; Choi, H. D.

    2012-01-01

    A new cold neutron source at the HANARO Research Reactor had been constructed in the framework of a five-year project, and ended in 2009. It has seven neutron guides, among which five guides were already allocated for a number of neutron scattering instruments. A new two-year project to develop a Cold Neutron Activation Station (CONAS) was carried out at the two neutron guides since May 2010, which was supported by the program of the Ministry of Education, Science and Technology, Korea. Fig. 1 shows the location of CONAS. CONAS is a complex facility including several radioanalytical instruments utilizing neutron capture reaction to analyze elements in a sample. It was designed to include three instruments like a CN-PGAA (Cold Neutron - Prompt Gamma Activation Analysis), a CN-NIPS (Cold Neutron - Neutron Induced Pair Spectrometer), and a CN-NDP (Cold Neutron - Neutron-induced prompt charged particle Depth Profiling). Fig. 2 shows the conceptual configuration of the CONAS concrete bioshield and the instruments. CN-PGAA and CN-NIPS measure the gamma-rays promptly emitted from the sample after neutron capture, whereas CN-NDP is a probe to measure the charged particles emitted from the sample surface after neutron capture. For this, we constructed two cold neutron guides called CG1 and CG2B guides from the CNS

  18. Support for cold neutron utilization

    International Nuclear Information System (INIS)

    Lee, Kye Hong; Han, Young Soo; Choi, Sungmin; Choi, Yong; Kwon, Hoon; Lee, Kwang Hee

    2012-06-01

    - Support for experiments by users of cold neutron scattering instrument - Short-term training of current and potential users of cold neutron scattering instrument for their effective use of the instrument - International collaboration for advanced utilization of cold neutron scattering instruments - Selection and training of qualified instrument scientists for vigorous research endeavors and outstanding achievements in experiments with cold neutron - Research on nano/bio materials using cold neutron scattering instruments - Bulk nano structure measurement using small angle neutron scattering and development of analysis technique

  19. Antimicrobial activity and the mechanism of silver nanoparticle thermosensitive gel

    Directory of Open Access Journals (Sweden)

    Chen M

    2011-11-01

    Full Text Available Meiwan Chen1,2,‡, Zhiwen Yang1,‡, Hongmei Wu1, Xin Pan1, Xiaobao Xie3, Chuanbin Wu11Research and Development Center of Pharmaceutical Engineering, School of Pharmaceutical Sciences, Sun Yat-sen University, Guangzhou, China; 2State Key Laboratory of Quality Research in Chinese Medicine, Institute of Chinese Medical Sciences, University of Macau, Macau, China; 3Guangdong Provincial Key Laboratory of Microbial Culture Collection and Application, Guangzhou, China ‡These authors contributed equally to this workPurpose: The purpose of the present study was to elucidate the antimicrobial activity and mechanism of silver nanoparticles incorporated into thermosensitive gel (S-T-Gel on Staphylococcus aureus, Escherichia coli, and Pseudomonas aeruginosa.Patients and methods: This study investigated the growth, permeability, and morphology of Staphylococcus aureus, Escherichia coli, and Pseudomonas aeruginosa cells in order to observe the action of S-T-Gel on the membrane structure of these three bacteria. The cell morphology of normal and treated bacteria cells was assessed by transmission electron microscopy (TEM, and the effects of S-T-Gel on genome DNA of bacterial cells were evaluated by agarose gel electrophoresis.Results: S-T-Gel showed promising activity against Staphylococcus aureus and moderate activity against Escherichia coli and Pseudomonas aeruginosa. The observation with TEM suggested that S-T-Gel may destroy the structure of bacterial cell membranes in order to enter the bacterial cell. S-T-Gel then condensed DNA and combined and coagulated with the cytoplasm of the damaged bacteria, resulting in the leakage of the cytoplasmic component and the eventual death of these three bacteria. In addition, the analysis of agarose gel electrophoresis demonstrated that S-T-Gel could increase the decomposability of genome DNA.Conclusion: These results about promising antimicrobial activity and mechanism of S-T-Gel may be useful for further research

  20. Cold temperatures increase cold hardiness in the next generation Ophraella communa beetles.

    Directory of Open Access Journals (Sweden)

    Zhong-Shi Zhou

    Full Text Available The leaf beetle, Ophraella communa, has been introduced to control the spread of the common ragweed, Ambrosia artemisiifolia, in China. We hypothesized that the beetle, to be able to track host-range expansion into colder climates, can phenotypically adapt to cold temperatures across generations. Therefore, we questioned whether parental experience of colder temperatures increases cold tolerance of the progeny. Specifically, we studied the demography, including development, fecundity, and survival, as well as physiological traits, including supercooling point (SCP, water content, and glycerol content of O. communa progeny whose parents were maintained at different temperature regimes. Overall, the entire immature stage decreased survival of about 0.2%-4.2% when parents experienced cold temperatures compared to control individuals obtained from parents raised at room temperature. However, intrinsic capacity for increase (r, net reproductive rate (R 0 and finite rate of increase (λ of progeny O. communa were maximum when parents experienced cold temperatures. Glycerol contents of both female and male in progeny was significantly higher when maternal and paternal adults were cold acclimated as compared to other treatments. This resulted in the supercooling point of the progeny adults being significantly lower compared to beetles emerging from parents that experienced room temperatures. These results suggest that cold hardiness of O. communa can be promoted by cold acclimation in previous generation, and it might counter-balance reduced survival in the next generation, especially when insects are tracking their host-plants into colder climates.

  1. BlastNeuron for Automated Comparison, Retrieval and Clustering of 3D Neuron Morphologies.

    Science.gov (United States)

    Wan, Yinan; Long, Fuhui; Qu, Lei; Xiao, Hang; Hawrylycz, Michael; Myers, Eugene W; Peng, Hanchuan

    2015-10-01

    Characterizing the identity and types of neurons in the brain, as well as their associated function, requires a means of quantifying and comparing 3D neuron morphology. Presently, neuron comparison methods are based on statistics from neuronal morphology such as size and number of branches, which are not fully suitable for detecting local similarities and differences in the detailed structure. We developed BlastNeuron to compare neurons in terms of their global appearance, detailed arborization patterns, and topological similarity. BlastNeuron first compares and clusters 3D neuron reconstructions based on global morphology features and moment invariants, independent of their orientations, sizes, level of reconstruction and other variations. Subsequently, BlastNeuron performs local alignment between any pair of retrieved neurons via a tree-topology driven dynamic programming method. A 3D correspondence map can thus be generated at the resolution of single reconstruction nodes. We applied BlastNeuron to three datasets: (1) 10,000+ neuron reconstructions from a public morphology database, (2) 681 newly and manually reconstructed neurons, and (3) neurons reconstructions produced using several independent reconstruction methods. Our approach was able to accurately and efficiently retrieve morphologically and functionally similar neuron structures from large morphology database, identify the local common structures, and find clusters of neurons that share similarities in both morphology and molecular profiles.

  2. TRPA1 is functionally expressed primarily by IB4-binding, non-peptidergic mouse and rat sensory neurons.

    Directory of Open Access Journals (Sweden)

    Marie E Barabas

    Full Text Available Subpopulations of somatosensory neurons are characterized by functional properties and expression of receptor proteins and surface markers. CGRP expression and IB4-binding are commonly used to define peptidergic and non-peptidergic subpopulations. TRPA1 is a polymodal, plasma membrane ion channel that contributes to mechanical and cold hypersensitivity during tissue injury, making it a key target for pain therapeutics. Some studies have shown that TRPA1 is predominantly expressed by peptidergic sensory neurons, but others indicate that TRPA1 is expressed extensively within non-peptidergic, IB4-binding neurons. We used FURA-2 calcium imaging to define the functional distribution of TRPA1 among peptidergic and non-peptidergic adult mouse (C57BL/6J DRG neurons. Approximately 80% of all small-diameter (<27 µm neurons from lumbar 1-6 DRGs that responded to TRPA1 agonists allyl isothiocyanate (AITC; 79% or cinnamaldehyde (84% were IB4-positive. Retrograde labeling via plantar hind paw injection of WGA-Alexafluor594 showed similarly that most (81% cutaneous neurons responding to TRPA1 agonists were IB4-positive. Additionally, we cultured DRG neurons from a novel CGRP-GFP mouse where GFP expression is driven by the CGRPα promoter, enabling identification of CGRP-expressing live neurons. Interestingly, 78% of TRPA1-responsive neurons were CGRP-negative. Co-labeling with IB4 revealed that the majority (66% of TRPA1 agonist responders were IB4-positive but CGRP-negative. Among TRPA1-null DRGs, few small neurons (2-4% responded to either TRPA1 agonist, indicating that both cinnamaldehyde and AITC specifically target TRPA1. Additionally, few large neurons (≥27 µm diameter responded to AITC (6% or cinnamaldehyde (4%, confirming that most large-diameter somata lack functional TRPA1. Comparison of mouse and rat DRGs showed that the majority of TRPA1-responsive neurons in both species were IB4-positive. Together, these data demonstrate that TRPA1 is

  3. TRPA1 Is Functionally Expressed Primarily by IB4-Binding, Non-Peptidergic Mouse and Rat Sensory Neurons

    Science.gov (United States)

    Stucky, Cheryl L.

    2012-01-01

    Subpopulations of somatosensory neurons are characterized by functional properties and expression of receptor proteins and surface markers. CGRP expression and IB4-binding are commonly used to define peptidergic and non-peptidergic subpopulations. TRPA1 is a polymodal, plasma membrane ion channel that contributes to mechanical and cold hypersensitivity during tissue injury, making it a key target for pain therapeutics. Some studies have shown that TRPA1 is predominantly expressed by peptidergic sensory neurons, but others indicate that TRPA1 is expressed extensively within non-peptidergic, IB4-binding neurons. We used FURA-2 calcium imaging to define the functional distribution of TRPA1 among peptidergic and non-peptidergic adult mouse (C57BL/6J) DRG neurons. Approximately 80% of all small-diameter (neurons from lumbar 1–6 DRGs that responded to TRPA1 agonists allyl isothiocyanate (AITC; 79%) or cinnamaldehyde (84%) were IB4-positive. Retrograde labeling via plantar hind paw injection of WGA-Alexafluor594 showed similarly that most (81%) cutaneous neurons responding to TRPA1 agonists were IB4-positive. Additionally, we cultured DRG neurons from a novel CGRP-GFP mouse where GFP expression is driven by the CGRPα promoter, enabling identification of CGRP-expressing live neurons. Interestingly, 78% of TRPA1-responsive neurons were CGRP-negative. Co-labeling with IB4 revealed that the majority (66%) of TRPA1 agonist responders were IB4-positive but CGRP-negative. Among TRPA1-null DRGs, few small neurons (2–4%) responded to either TRPA1 agonist, indicating that both cinnamaldehyde and AITC specifically target TRPA1. Additionally, few large neurons (≥27 µm diameter) responded to AITC (6%) or cinnamaldehyde (4%), confirming that most large-diameter somata lack functional TRPA1. Comparison of mouse and rat DRGs showed that the majority of TRPA1-responsive neurons in both species were IB4-positive. Together, these data demonstrate that TRPA1 is functionally expressed

  4. PHYSIOLOGICAL AND LEUKOCYTE SUBSET RESPONSES TO EXERCISE AND COLD EXPOSURE IN COLD-ACCLIMATIZED SKATERS

    Directory of Open Access Journals (Sweden)

    K. Kim

    2014-07-01

    Full Text Available We investigated physiological responses and changes in circulating immune cells following exercise in cold and thermoneutral conditions. Participants were short track skaters (n=9 who were acclimatized to cold conditions, and inline skaters (n=10 who were not acclimatized. All skaters were young, and skating at a recreational level three days per week for at least one year. Using a cross-over design, study variables were measured during 60 min of submaximal cycling (65% ·VO2max in cold (ambient temperature: 5±1°C, relative humidity: 41±9% and thermoneutral conditions (ambient temperature: 21±1°C, relative humidity: 35±5%. Heart rate, blood lactate and tympanic temperature were measured at rest, during exercise and recovery. Plasma cortisol, calprotectin and circulating blood cell numbers were measured before and after 60 min of cold or thermoneutral conditions, and during recovery from exercise. Heart rate was lower in both groups during exercise in cold versus thermoneutral conditions (P<0.05. The increase in total leukocytes during recovery was primarily due to an increase in neutrophils in both groups. The cold-acclimatized group activated neutrophils after exercise in cold exposure, whereas the non-acclimatized group activated lymphocyte and cortisol after exercise in cold exposure. Lymphocyte subsets significantly changed in both groups over time during recovery as compared to rest. Immediately after exercise in both groups, CD16+ and CD69+ cells were elevated compared to rest or before exercise in both conditions. Acclimatization to exercise in the cold does not appear to influence exercise-induced immune changes in cold conditions, with the possible exception of neutrophils, lymphocytes and cortisol concentration.

  5. Gemcitabine treatment of rat soft tissue sarcoma with phosphatidyldiglycerol-based thermosensitive liposomes.

    Science.gov (United States)

    Limmer, Simone; Hahn, Jasmin; Schmidt, Rebecca; Wachholz, Kirsten; Zengerle, Anja; Lechner, Katharina; Eibl, Hansjörg; Issels, Rolf D; Hossann, Martin; Lindner, Lars H

    2014-09-01

    The pyrimidine analogue gemcitabine (dFdC) is frequently used in the treatment of patients with solid tumors. However, after i.v. application dFdC is rapidly inactivated by metabolization. Here, the potential of thermosensitive liposomes based on 1,2-dipalmitoyl-sn-glycero-3-phosphodiglycerol (DPPG2-TSL) were investigated as carrier and targeting system for delivery of dFdC in combination with local hyperthermia (HT). DPPG2-TSL were prepared by the lipid film hydration and extrusion method and characterized by dynamic light scattering, thin layer chromatography, phosphate assay and HPLC. In vivo experiments were performed in Brown Norway rats with a syngeneic soft tissue sarcoma. Local HT treatment was performed by light exposure. DPPG2-TSL were stable at 37°C in serum and showed a temperature dependent dFdC release >40°C. Plasma half-life of dFdC was strongly increased from 0.07 h (non-liposomal) to 0.53 h (liposomal, vesicle size 105 nm) or 2.59 h (liposomal, 129 nm). Therapy of BN175 tumors with dFdC encapsulated in DPPG2-TSL + HT showed significant improvement in tumor growth delay compared to non-liposomal dFdC without HT (p < 0.05), non-liposomal dFdC with HT (p < 0.01), and liposomal dFdC without HT (p < 0.05), respectively. Gemcitabine encapsulated in DPPG2-TSL in combination with local HT is a promising tool for the treatment of solid tumors. Therefore, these encouraging results ask for further investigation and evaluation.

  6. Cold fusion, Alchemist's dream

    International Nuclear Information System (INIS)

    Clayton, E.D.

    1989-09-01

    In this report the following topics relating to cold fusion are discussed: muon catalysed cold fusion; piezonuclear fusion; sundry explanations pertaining to cold fusion; cosmic ray muon catalysed cold fusion; vibrational mechanisms in excited states of D 2 molecules; barrier penetration probabilities within the hydrogenated metal lattice/piezonuclear fusion; branching ratios of D 2 fusion at low energies; fusion of deuterons into 4 He; secondary D+T fusion within the hydrogenated metal lattice; 3 He to 4 He ratio within the metal lattice; shock induced fusion; and anomalously high isotopic ratios of 3 He/ 4 He

  7. Heparin-Poloxamer Thermosensitive Hydrogel Loaded with bFGF and NGF Enhances Peripheral Nerve Regeneration in Diabetic Rats.

    Science.gov (United States)

    Li, Rui; Li, Yiyang; Wu, Yanqing; Zhao, Yingzheng; Chen, Huanwen; Yuan, Yuan; Xu, Ke; Zhang, Hongyu; Lu, Yingfeng; Wang, Jian; Li, Xiaokun; Jia, Xiaofeng; Xiao, Jian

    2018-06-01

    Peripheral nerve injury (PNI) is a major burden to society with limited therapeutic options, and novel biomaterials have great potential for shifting the current paradigm of treatment. With a rising prevalence of chronic illnesses such as diabetes mellitus (DM), treatment of PNI is further complicated, and only few studies have proposed therapies suitable for peripheral nerve regeneration in DM. To provide a supportive environment to restore structure and/or function of nerves in DM, we developed a novel thermo-sensitive heparin-poloxamer (HP) hydrogel co-delivered with basic fibroblast growth factor (bFGF) and nerve growth factor (NGF) in diabetic rats with sciatic nerve crush injury. The delivery vehicle not only had a good affinity for large amounts of growth factors (GFs), but also controlled their release in a steady fashion, preventing degradation in vitro. In vivo, compared with HP hydrogel alone or direct GFs administration, GFs-HP hydrogel treatment is more effective at facilitating Schwann cell (SC) proliferation, leading to an increased expression of nerve associated structural proteins, enhanced axonal regeneration and remyelination, and improved recovery of motor function (all p nerve regeneration in patients with DM. Copyright © 2018 Elsevier Ltd. All rights reserved.

  8. Synthesis of high generation thermo-sensitive dendrimers for extraction of rivaroxaban from human fluid and pharmaceutic samples.

    Science.gov (United States)

    Parham, Negin; Panahi, Homayon Ahmad; Feizbakhsh, Alireza; Moniri, Elham

    2018-04-13

    In this present study, poly (N-isopropylacrylamide) as a thermo-sensitive agent was grafted onto magnetic nanoparticles, then ethylenediamine and methylmethacrylate were used to synthesize the first generation of poly amidoamine (PAMAM) dendrimers successively and the process continued alternatively until the ten generations of dendrimers. The synthesized nanocomposite was investigated using Fourier transform infrared spectrometry, thermalgravimetry analysis, X-ray diffractometry, elemental analysis and vibrating-sample magnetometer. The particle size and morphology were characterized using dynamic light scattering, field emission scanning electron microscopy and transmission electron microscopy. Batch experiments were conducted to investigate the parameters affecting adsorption and desorption of rivaroxaban by synthesized nanocomposite. The maximum sorption of rivaroxaban by the synthesized nanocomposite was obtained at pH of 8. The resulting grafted magnetic nanoparticle dendrimers were applied for extraction of rivaroxaban from biologic human liquids and medicinal samples. The specifications of rivaroxaban sorbed by a magnetic nanoparticle dendrimer showed good accessibility and high capacity of the active sites within the dendrimers. Urine and drug matrix extraction recoveries of more than 92.5 and 99.8 were obtained, respectively. Copyright © 2018 Elsevier B.V. All rights reserved.

  9. Formulation and evaluation of sublingual delivery of piroxicam using thermosensitive polymer with an inverted Franz diffusion cell.

    Science.gov (United States)

    Sivaraman, Arunprasad; Banga, Ajay K

    2016-01-01

    The aim of the study was to prepare a sublingual formulation for piroxicam using a thermosensitive polymer and to evaluate its permeation through porcine sublingual mucosa. Formulation technique utilized the transition property of poloxamer from solution state at room temperature to gel state at oromucosal temperature (37 °C). The permeation of the drug was evaluated using an inverted Franz diffusion cell technique that allowed the dosage form to be directly applied onto the substrate with required volume of saliva. The formulation was characterized for microscopy of the piroxicam crystals, sol-gel transition property and in-vitro diffusion study. Poloxamer-based formulation enhanced solubility and increased permeability of the piroxicam. Poloxamer formulation with 0.1% w/w piroxicam delivered a cumulative amount of 11.99 ± 7.82 and 11.23 ± 1.79 μg/cm(2), while non-poloxamer formulation delivered 3.57 ± 2.20 and 4.60 ± 6.90 μg/cm(2) with 0.1 and 0.5 ml artificial saliva, respectively, through porcine sublingual tissue in 6 h. A similar delivery profile was observed for 0.05% w/w piroxicam formulation as well. © 2015 Royal Pharmaceutical Society.

  10. Cold neutron production and application

    International Nuclear Information System (INIS)

    Inoue, Kazuhiko; Watanabe, Noboru.

    1976-01-01

    The first part gives general introduction to cold neutrons, namely the definition and the role as a probe in basic science and technology. The second part reviews various methods of cold neutron production. Some physical characteristics required for cold moderators are presented, and a list summarizes a number of cold moderators and their reactor physics constants. The definition of flux gain factor and the measured values for liquid light- and heavy-hydrogen are also given. The cold neutron spectra in methane and liquid hydrogen measured by LINAC time-of-flight method are presented to show the advantage of solid methane. The cold neutron sources using experimental reactors or linear accelerators are explained along with the examples of existing facilities. Two Japanese programs, the one is the use of a high flux reactor and the other is the use of a LINAC, are also presented. The third part of this report reviews the application areas of cold neutrons. (Aoki, K.)

  11. Labeling of neuronal differentiation and neuron cells with biocompatible fluorescent nanodiamonds.

    Science.gov (United States)

    Hsu, Tzu-Chia; Liu, Kuang-Kai; Chang, Huan-Cheng; Hwang, Eric; Chao, Jui-I

    2014-05-16

    Nanodiamond is a promising carbon nanomaterial developed for biomedical applications. Here, we show fluorescent nanodiamond (FND) with the biocompatible properties that can be used for the labeling and tracking of neuronal differentiation and neuron cells derived from embryonal carcinoma stem (ECS) cells. The fluorescence intensities of FNDs were increased by treatment with FNDs in both the mouse P19 and human NT2/D1 ECS cells. FNDs were taken into ECS cells; however, FNDs did not alter the cellular morphology and growth ability. Moreover, FNDs did not change the protein expression of stem cell marker SSEA-1 of ECS cells. The neuronal differentiation of ECS cells could be induced by retinoic acid (RA). Interestingly, FNDs did not affect on the morphological alteration, cytotoxicity and apoptosis during the neuronal differentiation. Besides, FNDs did not alter the cell viability and the expression of neuron-specific marker β-III-tubulin in these differentiated neuron cells. The existence of FNDs in the neuron cells can be identified by confocal microscopy and flow cytometry. Together, FND is a biocompatible and readily detectable nanomaterial for the labeling and tracking of neuronal differentiation process and neuron cells from stem cells.

  12. Heavy metals in locus ceruleus and motor neurons in motor neuron disease.

    Science.gov (United States)

    Pamphlett, Roger; Kum Jew, Stephen

    2013-12-12

    The causes of sporadic amyotrophic lateral sclerosis (SALS) and other types of motor neuron disease (MND) remain largely unknown. Heavy metals have long been implicated in MND, and it has recently been shown that inorganic mercury selectively enters human locus ceruleus (LC) and motor neurons. We therefore used silver nitrate autometallography (AMG) to look for AMG-stainable heavy metals (inorganic mercury and bismuth) in LC and motor neurons of 24 patients with MND (18 with SALS and 6 with familial MND) and in the LC of 24 controls. Heavy metals in neurons were found in significantly more MND patients than in controls when comparing: (1) the presence of any versus no heavy metal-containing LC neurons (MND 88%, controls 42%), (2) the median percentage of heavy metal-containing LC neurons (MND 9.5%, control 0.0%), and (3) numbers of individuals with heavy metal-containing LC neurons in the upper half of the percentage range (MND 75%, controls 25%). In MND patients, 67% of remaining spinal motor neurons contained heavy metals; smaller percentages were found in hypoglossal, nucleus ambiguus and oculomotor neurons, but none in cortical motor neurons. The majority of MND patients had heavy metals in both LC and spinal motor neurons. No glia or other neurons, including neuromelanin-containing neurons of the substantia nigra, contained stainable heavy metals. Uptake of heavy metals by LC and lower motor neurons appears to be fairly common in humans, though heavy metal staining in the LC, most likely due to inorganic mercury, was seen significantly more often in MND patients than in controls. The LC innervates many cell types that are affected in MND, and it is possible that MND is triggered by toxicant-induced interactions between LC and motor neurons.

  13. Heavy metals in locus ceruleus and motor neurons in motor neuron disease

    Science.gov (United States)

    2013-01-01

    Background The causes of sporadic amyotrophic lateral sclerosis (SALS) and other types of motor neuron disease (MND) remain largely unknown. Heavy metals have long been implicated in MND, and it has recently been shown that inorganic mercury selectively enters human locus ceruleus (LC) and motor neurons. We therefore used silver nitrate autometallography (AMG) to look for AMG-stainable heavy metals (inorganic mercury and bismuth) in LC and motor neurons of 24 patients with MND (18 with SALS and 6 with familial MND) and in the LC of 24 controls. Results Heavy metals in neurons were found in significantly more MND patients than in controls when comparing: (1) the presence of any versus no heavy metal-containing LC neurons (MND 88%, controls 42%), (2) the median percentage of heavy metal-containing LC neurons (MND 9.5%, control 0.0%), and (3) numbers of individuals with heavy metal-containing LC neurons in the upper half of the percentage range (MND 75%, controls 25%). In MND patients, 67% of remaining spinal motor neurons contained heavy metals; smaller percentages were found in hypoglossal, nucleus ambiguus and oculomotor neurons, but none in cortical motor neurons. The majority of MND patients had heavy metals in both LC and spinal motor neurons. No glia or other neurons, including neuromelanin-containing neurons of the substantia nigra, contained stainable heavy metals. Conclusions Uptake of heavy metals by LC and lower motor neurons appears to be fairly common in humans, though heavy metal staining in the LC, most likely due to inorganic mercury, was seen significantly more often in MND patients than in controls. The LC innervates many cell types that are affected in MND, and it is possible that MND is triggered by toxicant-induced interactions between LC and motor neurons. PMID:24330485

  14. Cold-Weather Sports

    Science.gov (United States)

    ... Videos for Educators Search English Español Cold-Weather Sports KidsHealth / For Teens / Cold-Weather Sports What's in this article? What to Do? Classes ... weather. What better time to be outdoors? Winter sports can help you burn calories, increase your cardiovascular ...

  15. Imaging of intracranial neuronal and mixed neuronal-glial tumours

    International Nuclear Information System (INIS)

    Cui Shimin; Qin Jinxi; Zhang Leili; Liu Meili; Jin Song; Yan Shixin; Liu Li; Dai Weiying; Li Tao; Gao Man

    2001-01-01

    Objective: To investigate the characteristic clinical, imaging , and pathologic findings of intracranial neuronal and mixed neuronal-glial tumours. Methods: The imaging findings of surgery and pathobiology proved intracranial neuronal and mixed neuronal-glial tumours in 14 cases (7 male and 7 female, ranging in age from 6-56 years; mean age 33.8 years) were retrospectively analyzed. Results: Eight gangliogliomas were located in the frontal lobe (4 cases), temporal lobe (1 case), front- temporal lobe (2 cases), and pons (1 case). They appeared as iso-or low density on CT, iso-or low signal intensity on T 1 WI, and high signal intensity on T 2 WI on MR imaging. Two central neurocytomas were located in the supratentorial ventricles. Four desmoplastic gangliogliomas were seen as cystic masses, appearing as low signal intensity on T 1 WI and high signal intensity on T 2 WI. Conclusion: Intracranial neuronal and mixed neuronal-glial tumours had imaging characteristics. Combined with clinical history, it was possible to make a tendency preoperative diagnosis using CT or MR

  16. Intrinsically active and pacemaker neurons in pluripotent stem cell-derived neuronal populations.

    Science.gov (United States)

    Illes, Sebastian; Jakab, Martin; Beyer, Felix; Gelfert, Renate; Couillard-Despres, Sébastien; Schnitzler, Alfons; Ritter, Markus; Aigner, Ludwig

    2014-03-11

    Neurons generated from pluripotent stem cells (PSCs) self-organize into functional neuronal assemblies in vitro, generating synchronous network activities. Intriguingly, PSC-derived neuronal assemblies develop spontaneous activities that are independent of external stimulation, suggesting the presence of thus far undetected intrinsically active neurons (IANs). Here, by using mouse embryonic stem cells, we provide evidence for the existence of IANs in PSC-neuronal networks based on extracellular multielectrode array and intracellular patch-clamp recordings. IANs remain active after pharmacological inhibition of fast synaptic communication and possess intrinsic mechanisms required for autonomous neuronal activity. PSC-derived IANs are functionally integrated in PSC-neuronal populations, contribute to synchronous network bursting, and exhibit pacemaker properties. The intrinsic activity and pacemaker properties of the neuronal subpopulation identified herein may be particularly relevant for interventions involving transplantation of neural tissues. IANs may be a key element in the regulation of the functional activity of grafted as well as preexisting host neuronal networks.

  17. Cold fusion

    International Nuclear Information System (INIS)

    Koster, J.

    1989-01-01

    In this contribution the author the phenomenom of so-called cold fusion, inspired by the memorable lecture of Moshe Gai on his own search for this effect. Thus much of what follows was presented by Dr. Gai; the rest is from independent reading. What is referred to as cold fusion is of course the observation of possible products of deuteron-deuteron (d-d) fusion within deuterium-loaded (dentended) electrodes. The debate over the two vanguard cold fusion experiments has raged under far more public attention than usually accorded new scientific phenomena. The clamor commenced with the press conference of M. Fleishmann and S. Pons on March 23, 1989 and the nearly simultaneous wide circulation of a preprint of S. Jones and collaborators. The majority of work attempting to confirm these observations has at the time of this writing yet to appear in published form, but contributions to conferences and electronic mail over computer networks were certainly filled with preliminary results. To keep what follows to a reasonable length the author limit this discussion to the searches for neutron (suggested by ref. 2) or for excessive heat production (suggested by ref. 1), following a synopsis of the hypotheses of cold fusion

  18. Glutamate neurons are intermixed with midbrain dopamine neurons in nonhuman primates and humans

    Science.gov (United States)

    Root, David H.; Wang, Hui-Ling; Liu, Bing; Barker, David J.; Mód, László; Szocsics, Péter; Silva, Afonso C.; Maglóczky, Zsófia; Morales, Marisela

    2016-01-01

    The rodent ventral tegmental area (VTA) and substantia nigra pars compacta (SNC) contain dopamine neurons intermixed with glutamate neurons (expressing vesicular glutamate transporter 2; VGluT2), which play roles in reward and aversion. However, identifying the neuronal compositions of the VTA and SNC in higher mammals has remained challenging. Here, we revealed VGluT2 neurons within the VTA and SNC of nonhuman primates and humans by simultaneous detection of VGluT2 mRNA and tyrosine hydroxylase (TH; for identification of dopamine neurons). We found that several VTA subdivisions share similar cellular compositions in nonhuman primates and humans; their rostral linear nuclei have a high prevalence of VGluT2 neurons lacking TH; their paranigral and parabrachial pigmented nuclei have mostly TH neurons, and their parabrachial pigmented nuclei have dual VGluT2-TH neurons. Within nonhuman primates and humans SNC, the vast majority of neurons are TH neurons but VGluT2 neurons were detected in the pars lateralis subdivision. The demonstration that midbrain dopamine neurons are intermixed with glutamate or glutamate-dopamine neurons from rodents to humans offers new opportunities for translational studies towards analyzing the roles that each of these neurons play in human behavior and in midbrain-associated illnesses such as addiction, depression, schizophrenia, and Parkinson’s disease. PMID:27477243

  19. Life-long stability of neurons: a century of research on neurogenesis, neuronal death and neuron quantification in adult CNS.

    Science.gov (United States)

    Turlejski, Kris; Djavadian, Ruzanna

    2002-01-01

    In this chapter we provide an extensive review of 100 years of research on the stability of neurons in the mammalian brain, with special emphasis on humans. Although Cajal formulated the Neuronal Doctrine, he was wrong in his beliefs that adult neurogenesis did not occur and adult neurons are dying throughout life. These two beliefs became accepted "common knowledge" and have shaped much of neuroscience research and provided much of the basis for clinical treatment of age-related brain diseases. In this review, we consider adult neurogenesis from a historical and evolutionary perspective. It is concluded, that while adult neurogenesis is a factor in the dynamics of the dentate gyrus and olfactory bulb, it is probably not a major factor during the life-span in most brain areas. Likewise, the acceptance of neuronal death as an explanation for normal age-related senility is challenged with evidence collected over the last fifty years. Much of the problem in changing this common belief of dying neurons was the inadequacies of neuronal counting methods. In this review we discuss in detail implications of recent improvements in neuronal quantification. We conclude: First, age-related neuronal atrophy is the major factor in functional deterioration of existing neurons and could be slowed down, or even reversed by various pharmacological interventions. Second, in most cases neuronal degeneration during aging is a pathology that in principle may be avoided. Third, loss of myelin and of the white matter is more frequent and important than the limited neuronal death in normal aging.

  20. Effect of salt on a thermosensitive mutant of Bacillus subtilis deficient in uracil and cell division

    International Nuclear Information System (INIS)

    Miyazaki, Nobuyoshi; Nagai, Kazuo; Tamura, Gakuzo

    1976-01-01

    A thermosensitive mutant ts 42, of Bacillus subtilis Marburg 168 thy trp2 which requires uracil, was examined as to the colony-forming ability at the permissive and nonpermissive temperatures. The viability of the mutant cells decreased rapidly at the restrictive temperature in modified woese's medium. However, the cells retained the viability when sodium succinate or potassium chloride was added to the medium at that temperature, although uranil deficiency was unchanged. A little but significant incorporation of adenine-8- 14 C into RNA still continued even after the incorporation of N-acetyl- 3 H-D-glucosamine into the acid-insoluble fraction of the cells terminated in the modified Woese's medium at 48 0 C. Both incorporations as well as the increase of absorbance were slowed down in the presence of sodium succinate at 48 0 C. This mutant, ts42, was more sensitive to deoxycholate than the parent wild strain. The resoration of the colony-forming ability after the temperature shifted back from 48 0 to 37 0 C was suppressed by the addition of deoxycholate to the medium. However, the cells became resistant to deoxycholate when uracil had been added to the medium prior to the temperature shift. (Kobatake, H.)

  1. Cold acclimation and cognitive performance: A review.

    Science.gov (United States)

    Jones, Douglas M; Bailey, Stephen P; Roelands, Bart; Buono, Michael J; Meeusen, Romain

    2017-12-01

    Athletes, occupational workers, and military personnel experience cold temperatures through cold air exposure or cold water immersion, both of which impair cognitive performance. Prior work has shown that neurophysiological pathways may be sensitive to the effects of temperature acclimation and, therefore, cold acclimation may be a potential strategy to attenuate cold-induced cognitive impairments for populations that are frequently exposed to cold environments. This review provides an overview of studies that examine repeated cold stress, cold acclimation, and measurements of cognitive performance to determine whether or not cold acclimation provides beneficial protection against cold-induced cognitive performance decrements. Studies included in this review assessed cognitive measures of reaction time, attention, logical reasoning, information processing, and memory. Repeated cold stress, with or without evidence of cold acclimation, appears to offer no added benefit of improving cognitive performance. However, research in this area is greatly lacking and, therefore, it is difficult to draw any definitive conclusions regarding the use of cold acclimation to improve cognitive performance during subsequent cold exposures. Given the current state of minimal knowledge on this topic, athletes, occupational workers, and military commands looking to specifically enhance cognitive performance in cold environments would likely not be advised to spend the time and effort required to become acclimated to cold. However, as more knowledge becomes available in this area, recommendations may change. Copyright © 2017 Elsevier B.V. All rights reserved.

  2. Role of neuronal activity in regulating the structure and function of auditory neurons

    International Nuclear Information System (INIS)

    Born, D.E.

    1986-01-01

    The role of afferent activity in maintaining neuronal structure and function was investigated in second order auditory neurons in nucleus magnocellularis (NM) of the chicken. The cochlea provides the major excitatory input to NM neurons via the eighth nerve. Removal of the cochlea causes dramatic changes in NM neurons. To determine if the elimination of neuronal activity is responsible for the changes in NM seen after cochlea removal, tetrodotoxin was used block action potentials in the cochlear ganglion cells. Tetrodotoxin injections into the perilymph reliably blocked neuronal activity in the cochlear nerve and NM. Far field recordings of sound-evoked potentials revealed that responses returned within 6 hours. Changes in amino acid incorporation in NM neurons were measured by giving intracardiac injections of 3 H-leucine and preparing tissue for autoradiographic demonstration of incorporated amino acid. Grain counts over individual neurons revealed that a single injection of tetrodotoxin produced a 40% decrease in grain density in ipsilateral NM neurons. It is concluded that neuronal activity plays an important contribution to the maintenance of the normal properties of NM neurons

  3. NeuronMetrics: software for semi-automated processing of cultured neuron images.

    Science.gov (United States)

    Narro, Martha L; Yang, Fan; Kraft, Robert; Wenk, Carola; Efrat, Alon; Restifo, Linda L

    2007-03-23

    Using primary cell culture to screen for changes in neuronal morphology requires specialized analysis software. We developed NeuronMetrics for semi-automated, quantitative analysis of two-dimensional (2D) images of fluorescently labeled cultured neurons. It skeletonizes the neuron image using two complementary image-processing techniques, capturing fine terminal neurites with high fidelity. An algorithm was devised to span wide gaps in the skeleton. NeuronMetrics uses a novel strategy based on geometric features called faces to extract a branch number estimate from complex arbors with numerous neurite-to-neurite contacts, without creating a precise, contact-free representation of the neurite arbor. It estimates total neurite length, branch number, primary neurite number, territory (the area of the convex polygon bounding the skeleton and cell body), and Polarity Index (a measure of neuronal polarity). These parameters provide fundamental information about the size and shape of neurite arbors, which are critical factors for neuronal function. NeuronMetrics streamlines optional manual tasks such as removing noise, isolating the largest primary neurite, and correcting length for self-fasciculating neurites. Numeric data are output in a single text file, readily imported into other applications for further analysis. Written as modules for ImageJ, NeuronMetrics provides practical analysis tools that are easy to use and support batch processing. Depending on the need for manual intervention, processing time for a batch of approximately 60 2D images is 1.0-2.5 h, from a folder of images to a table of numeric data. NeuronMetrics' output accelerates the quantitative detection of mutations and chemical compounds that alter neurite morphology in vitro, and will contribute to the use of cultured neurons for drug discovery.

  4. Human whole body cold adaptation.

    OpenAIRE

    Daanen, Hein A.M.; Van Marken Lichtenbelt, Wouter D.

    2016-01-01

    ABSTRACT Reviews on whole body human cold adaptation generally do not distinguish between population studies and dedicated acclimation studies, leading to confusing results. Population studies show that indigenous black Africans have reduced shivering thermogenesis in the cold and poor cold induced vasodilation in fingers and toes compared to Caucasians and Inuit. About 40,000?y after humans left Africa, natives in cold terrestrial areas seems to have developed not only behavioral adaptations...

  5. Neuronal-glial trafficking

    International Nuclear Information System (INIS)

    Bachelard, H.S.

    2001-01-01

    Full text: The name 'glia' originates from the Greek word for glue, because astro glia (or astrocytes) were thought only to provide an anatomical framework for the electrically-excitable neurones. However, awareness that astrocytes perform vital roles in protecting the neurones, which they surround, emerged from evidence that they act as neuroprotective K + -sinks, and that they remove potentially toxic extracellular glutamate from the vicinity of the neurones. The astrocytes convert the glutamate to non-toxic glutamine which is returned to the neurones and used to replenish transmitter glutamate. This 'glutamate-glutamine cycle' (established in the 1960s by Berl and his colleagues) also contributes to protecting the neurones against a build-up of toxic ammonia. Glial cells also supply the neurones with components for free-radical scavenging glutathione. Recent studies have revealed that glial cells play a more positive interactive role in furnishing the neurones with fuels. Studies using radioactive 14 C, 13 C-MRS and 15 N-GCMS have revealed that glia produce alanine, lactate and proline for consumption by neurones, with increased formation of neurotransmitter glutamate. On neuronal activation the release of NH 4 + and glutamate from the neurones stimulates glucose uptake and glycolysis in the glia to produce more alanine, which can be regarded as an 'alanine-glutamate cycle' Use of 14 C-labelled precursors provided early evidence that neurotransmitter GABA may be partly derived from glial glutamine, and this has been confirmed recently in vivo by MRS isotopomer analysis of the GABA and glutamine labelled from 13 C-acetate. Relative rates of intermediary metabolism in glia and neurones can be calculated using a combination of [1- 13 C] glucose and [1,2- 13 C] acetate. When glutamate is released by neurones there is a net neuronal loss of TCA intermediates which have to be replenished. Part of this is derived from carboxylation of pyruvate, (pyruvate carboxylase

  6. Human whole body cold adaptation.

    NARCIS (Netherlands)

    Daanen, Hein A.M.; Van Marken Lichtenbelt, Wouter D.

    2016-01-01

    Reviews on whole body human cold adaptation generally do not distinguish between population studies and dedicated acclimation studies, leading to confusing results. Population studies show that indigenous black Africans have reduced shivering thermogenesis in the cold and poor cold induced

  7. Reconstruction of phrenic neuron identity in embryonic stem cell-derived motor neurons.

    Science.gov (United States)

    Machado, Carolina Barcellos; Kanning, Kevin C; Kreis, Patricia; Stevenson, Danielle; Crossley, Martin; Nowak, Magdalena; Iacovino, Michelina; Kyba, Michael; Chambers, David; Blanc, Eric; Lieberam, Ivo

    2014-02-01

    Air breathing is an essential motor function for vertebrates living on land. The rhythm that drives breathing is generated within the central nervous system and relayed via specialised subsets of spinal motor neurons to muscles that regulate lung volume. In mammals, a key respiratory muscle is the diaphragm, which is innervated by motor neurons in the phrenic nucleus. Remarkably, relatively little is known about how this crucial subtype of motor neuron is generated during embryogenesis. Here, we used direct differentiation of motor neurons from mouse embryonic stem cells as a tool to identify genes that direct phrenic neuron identity. We find that three determinants, Pou3f1, Hoxa5 and Notch, act in combination to promote a phrenic neuron molecular identity. We show that Notch signalling induces Pou3f1 in developing motor neurons in vitro and in vivo. This suggests that the phrenic neuron lineage is established through a local source of Notch ligand at mid-cervical levels. Furthermore, we find that the cadherins Pcdh10, which is regulated by Pou3f1 and Hoxa5, and Cdh10, which is controlled by Pou3f1, are both mediators of like-like clustering of motor neuron cell bodies. This specific Pcdh10/Cdh10 activity might provide the means by which phrenic neurons are assembled into a distinct nucleus. Our study provides a framework for understanding how phrenic neuron identity is conferred and will help to generate this rare and inaccessible yet vital neuronal subtype directly from pluripotent stem cells, thus facilitating subsequent functional investigations.

  8. Spectroscopy with cold and ultra-cold neutrons

    Directory of Open Access Journals (Sweden)

    Abele Hartmut

    2015-01-01

    Full Text Available We present two new types of spectroscopy methods for cold and ultra-cold neutrons. The first method, which uses the R×B drift effect to disperse charged particles in a uniformly curved magnetic field, allows to study neutron β-decay. We aim for a precision on the 10−4 level. The second method that we refer to as gravity resonance spectroscopy (GRS allows to test Newton’s gravity law at short distances. At the level of precision we are able to provide constraints on any possible gravity-like interaction. In particular, limits on dark energy chameleon fields are improved by several orders of magnitude.

  9. Cold recovery during regasification of LNG part one: Cold utilization far from the regasification facility

    International Nuclear Information System (INIS)

    La Rocca, Vincenzo

    2010-01-01

    The paper deals with cold recovery during LNG regasification. The applications analyzed pertain to the use in deep freezing agro food industry and in space air conditioning facilities in commercial sector (Supermarkets and Hypermarkets) of cold recovered from the regasification process. A modular LNG regasification unit is proposed having the regasification capacity of 2 BCM/year of gas and it is based on use of a Power Cycle working with Ethane, this unit allows operation of cold energy transfer, contained in LNG to be regasified, in a range of temperatures suitable for multipurpose use of cold, reducing regasification process irreversibility. Some electric energy is produced by the Power Cycle, but the purpose of the modular unit is to deliver cold suitable for industrial and commercial use in the proper temperature range utilizing Carbon dioxide as secondary fluid to transfer cold from regasification site to far end users. The subject is divided in two papers: this paper deals with facilities delivering cold released during LNG regasification and related pipeline facilities to transfer cold at far end users while the other paper pertains to analysis of end users applications. Results of a detailed thermodynamic and economic analysis demonstrate the suitability of the proposal.

  10. Sensation of Cold during the Ice Water Test Corresponds to the Perception of Pain during Botulinum Toxin Bladder Wall Injections.

    Science.gov (United States)

    Reitz, André; Hüsch, Tanja; Doggweiler, Regula; Buse, Stephan; Haferkamp, Axel

    2018-01-01

    To investigate the association of bladder cold sensation (BCS) during the ice water test (IWT) and pain perception when botulinum toxin injections (BTI) are administered into the bladder wall. In 86 patients with idiopathic overactive bladder, the BCS during the IWT was investigated. Patients were divided into 2 groups: with and without BCS. During subsequent administration of BTI, the number of perceived and painful injections as well as the pain levels on a 0-100 pain scale were compared in both groups using Student t test. Thirty-five patients reported a BCS, while 51 did not. After 10 BTI, the mean number of perceived injections was 7.9 in patients with and 2.4 in patients without BCS (p sensation (p perceptions of cold and pain in the urinary bladder may use similar receptors and neuronal pathways. © 2018 S. Karger AG, Basel.

  11. Energy-efficient neural information processing in individual neurons and neuronal networks.

    Science.gov (United States)

    Yu, Lianchun; Yu, Yuguo

    2017-11-01

    Brains are composed of networks of an enormous number of neurons interconnected with synapses. Neural information is carried by the electrical signals within neurons and the chemical signals among neurons. Generating these electrical and chemical signals is metabolically expensive. The fundamental issue raised here is whether brains have evolved efficient ways of developing an energy-efficient neural code from the molecular level to the circuit level. Here, we summarize the factors and biophysical mechanisms that could contribute to the energy-efficient neural code for processing input signals. The factors range from ion channel kinetics, body temperature, axonal propagation of action potentials, low-probability release of synaptic neurotransmitters, optimal input and noise, the size of neurons and neuronal clusters, excitation/inhibition balance, coding strategy, cortical wiring, and the organization of functional connectivity. Both experimental and computational evidence suggests that neural systems may use these factors to maximize the efficiency of energy consumption in processing neural signals. Studies indicate that efficient energy utilization may be universal in neuronal systems as an evolutionary consequence of the pressure of limited energy. As a result, neuronal connections may be wired in a highly economical manner to lower energy costs and space. Individual neurons within a network may encode independent stimulus components to allow a minimal number of neurons to represent whole stimulus characteristics efficiently. This basic principle may fundamentally change our view of how billions of neurons organize themselves into complex circuits to operate and generate the most powerful intelligent cognition in nature. © 2017 Wiley Periodicals, Inc. © 2017 Wiley Periodicals, Inc.

  12. A single-neuron tracing study of arkypallidal and prototypic neurons in healthy rats.

    Science.gov (United States)

    Fujiyama, Fumino; Nakano, Takashi; Matsuda, Wakoto; Furuta, Takahiro; Udagawa, Jun; Kaneko, Takeshi

    2016-12-01

    The external globus pallidus (GP) is known as a relay nucleus of the indirect pathway of the basal ganglia. Recent studies in dopamine-depleted and healthy rats indicate that the GP comprises two main types of pallidofugal neurons: the so-called "prototypic" and "arkypallidal" neurons. However, the reconstruction of complete arkypallidal neurons in healthy rats has not been reported. Here we visualized the entire axonal arborization of four single arkypallidal neurons and six single prototypic neurons in rat brain using labeling with a viral vector expressing membrane-targeted green fluorescent protein and examined the distribution of axon boutons in the target nuclei. Results revealed that not only the arkypallidal neurons but nearly all of the prototypic neurons projected to the striatum with numerous axon varicosities. Thus, the striatum is a major target nucleus for pallidal neurons. Arkypallidal and prototypic GP neurons located in the calbindin-positive and calbindin-negative regions mainly projected to the corresponding positive and negative regions in the striatum. Because the GP and striatum calbindin staining patterns reflect the topographic organization of the striatopallidal projection, the striatal neurons in the sensorimotor and associative regions constitute the reciprocal connection with the GP neurons in the corresponding regions.

  13. Tuning of thermally induced sol-to-gel transitions of moderately concentrated aqueous solutions of doubly thermosensitive hydrophilic diblock copolymers poly(methoxytri(ethylene glycol) acrylate)-b-poly(ethoxydi(ethylene glycol) acrylate-co-acrylic acid).

    Science.gov (United States)

    Jin, Naixiong; Zhang, Hao; Jin, Shi; Dadmun, Mark D; Zhao, Bin

    2012-03-15

    We report in this article a method to tune the sol-to-gel transitions of moderately concentrated aqueous solutions of doubly thermosensitive hydrophilic diblock copolymers that consist of two blocks exhibiting distinct lower critical solution temperatures (LCSTs) in water. A small amount of weak acid groups is statistically incorporated into the lower LCST block so that its LCST can be tuned by varying solution pH. Well-defined diblock copolymers, poly(methoxytri(ethylene glycol) acrylate)-b-poly(ethoxydi(ethylene glycol) acrylate-co-acrylic acid) (PTEGMA-b-P(DEGEA-co-AA)), were prepared by reversible addition-fragmentation chain transfer polymerization and postpolymerization modification. PTEGMA and PDEGEA are thermosensitive water-soluble polymers with LCSTs of 58 and 9 °C, respectively, in water. A 25 wt % aqueous solution of PTEGMA-b-P(DEGEA-co-AA) with a molar ratio of DEGEA to AA units of 100:5.2 at pH = 3.24 underwent multiple phase transitions upon heating, from a clear, free-flowing liquid (sol-to-gel transition temperature (T(sol-gel)) shifted to higher values, while the gel-to-sol transition (T(gel-sol)) and the clouding temperature (T(clouding)) of the sample remained essentially the same. These transitions and the tunability of T(sol-gel) originated from the thermosensitive properties of two blocks of the diblock copolymer and the pH dependence of the LCST of P(DEGEA-co-AA), which were confirmed by dynamic light scattering and differential scanning calorimetry studies. Using the vial inversion test method, we mapped out the C-shaped sol-gel phase diagrams of the diblock copolymer in aqueous buffers in the moderate concentration range at three different pH values (3.24, 5.58, and 5.82, all measured at ~0 °C). While the upper temperature boundaries overlapped, the lower temperature boundary shifted upward and the critical gelation concentration increased with the increase of pH. The AA content in PTEGMA-b-P(DEGEA-co-AA) was found to have a significant

  14. Therapeutic application of injectable thermosensitive hydrogel in preventing local breast cancer recurrence and improving incision wound healing in a mouse model

    Science.gov (United States)

    Lei, Na; Gong, Changyang; Qian, Zhiyong; Luo, Feng; Wang, Cheng; Wang, Helan; Wei, Yuquan

    2012-08-01

    Many drug delivery systems (DDSs) have been investigated for local targeting of malignant disease with the intention of increasing anti-tumor activity and minimizing systemic toxicity. An injectable thermosensitive hydrogel was applied to prevent locoregional recurrence of 4T1 breast cancer in a mouse model. The presented hydrogel, which is based on poly(ethyleneglycol)-poly(ε-caprolactone)-poly(ethylene glycol) (PEG-PCL-PEG, PECE), flows freely at normal temperature, forms a gel within seconds in situ at body temperature, and eventually releases the drug in a consistent and sustained fashion as it gradually biodegrades. Locoregional recurrence after primary tumor removal was significantly inhibited in mice treated with the paclitaxel (PTX)-loaded PECE hydrogel subcutaneously (9.1%) administered, compared with the blank hydrogel (80.0%), systemic (77.8%) and locally (75.0%) administered PTX, and the control group (100%) (P 0.05), in agreement with histopathological examinations. This novel DDSs represents a promising approach for local adjuvant therapy in malignant disease.

  15. Age and Ethnic Differences in Cold Weather and Contagion Theories of Colds and Flu

    Science.gov (United States)

    Sigelman, Carol K.

    2012-01-01

    Age and ethnic group differences in cold weather and contagion or germ theories of infectious disease were explored in two studies. A cold weather theory was frequently invoked to explain colds and to a lesser extent flu but became less prominent with age as children gained command of a germ theory of disease. Explanations of how contact with…

  16. Cerebellar Nuclear Neurons Use Time and Rate Coding to Transmit Purkinje Neuron Pauses.

    Science.gov (United States)

    Sudhakar, Shyam Kumar; Torben-Nielsen, Benjamin; De Schutter, Erik

    2015-12-01

    Neurons of the cerebellar nuclei convey the final output of the cerebellum to their targets in various parts of the brain. Within the cerebellum their direct upstream connections originate from inhibitory Purkinje neurons. Purkinje neurons have a complex firing pattern of regular spikes interrupted by intermittent pauses of variable length. How can the cerebellar nucleus process this complex input pattern? In this modeling study, we investigate different forms of Purkinje neuron simple spike pause synchrony and its influence on candidate coding strategies in the cerebellar nuclei. That is, we investigate how different alignments of synchronous pauses in synthetic Purkinje neuron spike trains affect either time-locking or rate-changes in the downstream nuclei. We find that Purkinje neuron synchrony is mainly represented by changes in the firing rate of cerebellar nuclei neurons. Pause beginning synchronization produced a unique effect on nuclei neuron firing, while the effect of pause ending and pause overlapping synchronization could not be distinguished from each other. Pause beginning synchronization produced better time-locking of nuclear neurons for short length pauses. We also characterize the effect of pause length and spike jitter on the nuclear neuron firing. Additionally, we find that the rate of rebound responses in nuclear neurons after a synchronous pause is controlled by the firing rate of Purkinje neurons preceding it.

  17. Cerebellar Nuclear Neurons Use Time and Rate Coding to Transmit Purkinje Neuron Pauses

    Science.gov (United States)

    Sudhakar, Shyam Kumar; Torben-Nielsen, Benjamin; De Schutter, Erik

    2015-01-01

    Neurons of the cerebellar nuclei convey the final output of the cerebellum to their targets in various parts of the brain. Within the cerebellum their direct upstream connections originate from inhibitory Purkinje neurons. Purkinje neurons have a complex firing pattern of regular spikes interrupted by intermittent pauses of variable length. How can the cerebellar nucleus process this complex input pattern? In this modeling study, we investigate different forms of Purkinje neuron simple spike pause synchrony and its influence on candidate coding strategies in the cerebellar nuclei. That is, we investigate how different alignments of synchronous pauses in synthetic Purkinje neuron spike trains affect either time-locking or rate-changes in the downstream nuclei. We find that Purkinje neuron synchrony is mainly represented by changes in the firing rate of cerebellar nuclei neurons. Pause beginning synchronization produced a unique effect on nuclei neuron firing, while the effect of pause ending and pause overlapping synchronization could not be distinguished from each other. Pause beginning synchronization produced better time-locking of nuclear neurons for short length pauses. We also characterize the effect of pause length and spike jitter on the nuclear neuron firing. Additionally, we find that the rate of rebound responses in nuclear neurons after a synchronous pause is controlled by the firing rate of Purkinje neurons preceding it. PMID:26630202

  18. Cold knife cone biopsy

    Science.gov (United States)

    ... biopsy; Pap smear - cone biopsy; HPV - cone biopsy; Human papilloma virus - cone biopsy; Cervix - cone biopsy; Colposcopy - cone biopsy Images Female reproductive anatomy Cold cone biopsy Cold cone removal References Baggish ...

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

    Science.gov (United States)

    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

  20. Cold water injection nozzles

    International Nuclear Information System (INIS)

    Kura, Masaaki; Maeda, Masamitsu; Endo, Takio.

    1979-01-01

    Purpose: To inject cold water in a reactor without applying heat cycles to a reactor container and to the inner wall of a feedwater nozzle by securing a perforated plate at the outlet of the cold water injection nozzle. Constitution: A disc-like cap is secured to the final end of a return nozzle of a control rod drive. The cap prevents the flow of a high temperature water flowing downward in the reactor from entering into the nozzle. The cap is perforated with a plurality of bore holes for injecting cold water into the reactor. The cap is made to about 100 mm in thickness so that the cold water passing through the bore holes is heated by the heat conduction in the cap. Accordingly, the flow of high temperature water flowing downwardly in the reactor is inhibited by the cap from backward flowing into the nozzle. Moreover, the flow of the cold water in the nozzle is controlled and rectified when passed through the bore holes in the cap and then injected into the reactor. (Yoshino, Y.)

  1. Cannabinoid 1 receptor knockout mice display cold allodynia, but enhanced recovery from spared-nerve injury-induced mechanical hypersensitivity.

    Science.gov (United States)

    Sideris, Alexandra; Piskoun, Boris; Russo, Lori; Norcini, Monica; Blanck, Thomas; Recio-Pinto, Esperanza

    2016-01-01

    The function of the Cannabinoid 1 receptor (CB1R) in the development of neuropathic pain is not clear. Mounting evidence suggest that CB1R expression and activation may contribute to pain. Cannabinoid 1 receptor knockout mice (CB1R-/-) generated on a C57Bl/6 background exhibit hypoalgesia in the hotplate assay and formalin test. These findings suggest that Cannabinoid 1 receptor expression mediates the responses to at least some types of painful stimuli. By using this mouse line, we sought to determine if the lack of Cannabinoid 1 receptor unveils a general hypoalgesic phenotype, including protection against the development of neuropathic pain. The acetone test was used to measure cold sensitivity, the electronic von Frey was used to measure mechanical thresholds before and after spared-nerve injury, and analysis of footprint patterns was conducted to determine if motor function is differentially affected after nerve-injury in mice with varying levels of Cannabinoid 1 receptor. At baseline, CB1R-/- mice were hypersensitive in the acetone test, and this phenotype was maintained after spared-nerve injury. Using calcium imaging of lumbar dorsal root ganglion (DRG) cultures, a higher percentage of neurons isolated from CB1R-/- mice were menthol sensitive relative to DRG isolated from wild-type (CB1R+/+) mice. Baseline mechanical thresholds did not differ among genotypes, and mechanical hypersensitivity developed similarly in the first two weeks following spared-nerve injury (SNI). At two weeks post-SNI, CB1R-/- mice recovered significantly from mechanical hypersensitivity, while the CB1R+/+ mice did not. Heterozygous knockouts (CB1R+/-) transiently developed cold allodynia only after injury, but recovered mechanical thresholds to a similar extent as the CB1R-/- mice. Sciatic functional indices, which reflect overall nerve health, and alternation coefficients, which indicate uniformity of strides, were not significantly different among genotypes. Cold allodynia and

  2. Development of cold neutron spectrometers

    International Nuclear Information System (INIS)

    Lee, Changhee; Lee, C. H.; So, J. Y.; Park, S.; Han, Y. S.; Cho, S. J.; Moon, M. K.; Choi, Y. H.; Sun, G. M.

    2012-03-01

    Cold Neutron Triple Axsis Spectrometer (Cold-TAS) Development Ο Fabrication and Installation of the Major Cold-TAS Components Ο Performance Test of the Cold-TAS □ Cold Neutron Time-of-Flight Spectrometer(DC-TOF) Development Ο Fabrication of the Major DC-TOF Components Ο Development DC-TOF Data Reduction Software □ Expected Contribution The two world-class inelastic neutron scattering instruments measure atomic or molecular scale dynamics of meV energy range. This unprecedented measurement capability in the country will enable domestic and international scientists to observe new phenomena in their materials research to obtain world class results. Especially those who work in the fields of magnetic properties of superconductors and multiferroics, molecular dynamics, etc. will get more benefit from these two instruments

  3. Cold perception and gene expression differ in Olea europaea seed coat and embryo during drupe cold acclimation.

    Science.gov (United States)

    D'Angeli, S; Falasca, G; Matteucci, M; Altamura, M M

    2013-01-01

    FAD2 and FAD7 desaturases are involved in cold acclimation of olive (Olea europaea) mesocarp. There is no research information available on cold acclimation of seeds during mesocarp cold acclimation or on differences in the cold response of the seed coat and embryo. How FAD2 and FAD7 affect seed coat and embryo cold responses is unknown. Osmotin positively affects cold acclimation in olive tree vegetative organs, but its role in the seeds requires investigation. OeFAD2.1, OeFAD2.2, OeFAD7 and Oeosmotin were investigated before and after mesocarp acclimation by transcriptomic, lipidomic and immunolabelling analyses, and cytosolic calcium concentration ([Ca(2+)](cyt)) signalling, F-actin changes and seed development were investigated by epifluorescence/histological analyses. Transient [Ca(2+)](cyt) rises and F-actin disassembly were found in cold-shocked protoplasts from the seed coat, but not from the embryo. The thickness of the outer endosperm cuticle increased during drupe exposure to lowering of temperature, whereas the embryo protoderm always lacked cuticle. OeFAD2 transcription increased in both the embryo and seed coat in the cold-acclimated drupe, but linoleic acid (i.e. the product of FAD2 activity) increased solely in the seed coat. Osmotin was immunodetected in the seed coat and endosperm of the cold-acclimated drupe, and not in the embryo. The results show cold responsiveness in the seed coat and cold tolerance in the embryo. We propose a role for the seed coat in maintaining embryo cold tolerance by increasing endosperm cutinization through FAD2 and osmotin activities. © 2012 The Authors. New Phytologist © 2012 New Phytologist Trust.

  4. Cold fusion research

    International Nuclear Information System (INIS)

    1989-11-01

    I am pleased to forward to you the Final Report of the Cold Fusion Panel. This report reviews the current status of cold fusion and includes major chapters on Calorimetry and Excess Heat, Fusion Products and Materials Characterization. In addition, the report makes a number of conclusions and recommendations, as requested by the Secretary of Energy

  5. COLD-WORKED HARDWARE

    Directory of Open Access Journals (Sweden)

    N. M. Strizhak

    2007-01-01

    Full Text Available The different types of cold-worked accessory are examined in the article. The necessity of development of such type of accessory in the Republic of Belarus due to requirements of market is shown. High emphasis is placed on the methods of increase of plasticity of cold-worked accessory from usual mill of RUP and CIS countries.

  6. Working in the Cold

    Centers for Disease Control (CDC) Podcasts

    During the winter, many workers are outdoors, working in cold, wet, icy, or snowy conditions. Learn how to identify symptoms that tell you there may be a problem and protect yourself from cold stress.

  7. Major differences observed in transcript profiles of blueberry during cold acclimation under field and cold room conditions.

    Science.gov (United States)

    Dhanaraj, Anik L; Alkharouf, Nadim W; Beard, Hunter S; Chouikha, Imed B; Matthews, Benjamin F; Wei, Hui; Arora, Rajeev; Rowland, Lisa J

    2007-02-01

    Our laboratory has been working toward increasing our understanding of the genetic control of cold hardiness in blueberry (Vaccinium section Cyanococcus) to ultimately use this information to develop more cold hardy cultivars for the industry. Here, we report using cDNA microarrays to monitor changes in gene expression at multiple times during cold acclimation under field and cold room conditions. Microarrays contained over 2,500 cDNA inserts, approximately half of which had been picked and single-pass sequenced from each of two cDNA libraries that were constructed from cold acclimated floral buds and non-acclimated floral buds of the fairly cold hardy cv. Bluecrop (Vaccinium corymbosum L.). Two biological samples were examined at each time point. Microarray data were analyzed statistically using t tests, ANOVA, clustering algorithms, and online analytical processing (OLAP). Interestingly, more transcripts were found to be upregulated under cold room conditions than under field conditions. Many of the genes induced only under cold room conditions could be divided into three major types: (1) genes associated with stress tolerance; (2) those that encode glycolytic and TCA cycle enzymes, and (3) those associated with protein synthesis machinery. A few of the genes induced only under field conditions appear to be related to light stress. Possible explanations for these differences are discussed in physiological context. Although many similarities exist in how plants respond during cold acclimation in the cold room and in the field environment, there are major differences suggesting caution should be taken in interpreting results based only on artificial, cold room conditions.

  8. NBLAST: Rapid, Sensitive Comparison of Neuronal Structure and Construction of Neuron Family Databases.

    Science.gov (United States)

    Costa, Marta; Manton, James D; Ostrovsky, Aaron D; Prohaska, Steffen; Jefferis, Gregory S X E

    2016-07-20

    Neural circuit mapping is generating datasets of tens of thousands of labeled neurons. New computational tools are needed to search and organize these data. We present NBLAST, a sensitive and rapid algorithm, for measuring pairwise neuronal similarity. NBLAST considers both position and local geometry, decomposing neurons into short segments; matched segments are scored using a probabilistic scoring matrix defined by statistics of matches and non-matches. We validated NBLAST on a published dataset of 16,129 single Drosophila neurons. NBLAST can distinguish neuronal types down to the finest level (single identified neurons) without a priori information. Cluster analysis of extensively studied neuronal classes identified new types and unreported topographical features. Fully automated clustering organized the validation dataset into 1,052 clusters, many of which map onto previously described neuronal types. NBLAST supports additional query types, including searching neurons against transgene expression patterns. Finally, we show that NBLAST is effective with data from other invertebrates and zebrafish. VIDEO ABSTRACT. Copyright © 2016 MRC Laboratory of Molecular Biology. Published by Elsevier Inc. All rights reserved.

  9. Impairment of exercise performance following cold water immersion is not attenuated after 7 days of cold acclimation.

    Science.gov (United States)

    Jones, Douglas M; Roelands, Bart; Bailey, Stephen P; Buono, Michael J; Meeusen, Romain

    2018-03-19

    It is well-documented that severe cold stress impairs exercise performance. Repeated immersion in cold water induces an insulative type of cold acclimation, wherein enhanced vasoconstriction leads to greater body heat retention, which may attenuate cold-induced exercise impairments. The purpose of this study, therefore, was to investigate changes in exercise performance during a 7-day insulative type of cold acclimation. Twelve healthy participants consisting of eight males and four females (mean ± SD age: 25.6 ± 5.2 years, height: 174.0 ± 8.9 cm, weight: 75.6 ± 13.1 kg) performed a 20 min self-paced cycling test in 23 °C, 40% humidity without prior cold exposure. Twenty-four hours later they began a 7-day cold acclimation protocol (daily 90 min immersion in 10 °C water). On days one, four, and seven of cold acclimation, participants completed the same cycling test. Measurements of work completed, core and skin temperatures, heart rate, skin blood flow, perceived exertion, and thermal sensation were measured during each cycling test. Successful insulative cold acclimation was observed. Work produced during the baseline cycling test (220 ± 70 kJ) was greater (p immersions (195 ± 58, 197 ± 60, and 194 ± 62 kJ) despite similar ratings of perceived exertion during each test, suggesting that cold exposure impaired cycling performance. This impairment, however, was not attenuated over the cold acclimation period. Results suggest that insulative cold acclimation does not attenuate impairments in exercise performance that were observed following acute cold water immersion.

  10. Direct projections from hypothalamic orexin neurons to brainstem cardiac vagal neurons.

    Science.gov (United States)

    Dergacheva, Olga; Yamanaka, Akihiro; Schwartz, Alan R; Polotsky, Vsevolod Y; Mendelowitz, David

    2016-12-17

    Orexin neurons are known to augment the sympathetic control of cardiovascular function, however the role of orexin neurons in parasympathetic cardiac regulation remains unclear. To test the hypothesis that orexin neurons contribute to parasympathetic control we selectively expressed channelrhodopsin-2 (ChR2) in orexin neurons in orexin-Cre transgenic rats and examined postsynaptic currents in cardiac vagal neurons (CVNs) in the dorsal motor nucleus of the vagus (DMV). Simultaneous photostimulation and recording in ChR2-expressing orexin neurons in the lateral hypothalamus resulted in reliable action potential firing as well as large whole-cell currents suggesting a strong expression of ChR2 and reliable optogenetic excitation. Photostimulation of ChR2-expressing fibers in the DMV elicited short-latency (ranging from 3.2ms to 8.5ms) postsynaptic currents in 16 out of 44 CVNs tested. These responses were heterogeneous and included excitatory glutamatergic (63%) and inhibitory GABAergic (37%) postsynaptic currents. The results from this study suggest different sub-population of orexin neurons may exert diverse influences on brainstem CVNs and therefore may play distinct functional roles in parasympathetic control of the heart. Copyright © 2016 IBRO. Published by Elsevier Ltd. All rights reserved.

  11. Synthesis and characterization of thermosensitive poly(organophosphazenes) with methoxy-poly(ethylene glycol) and alkylamines as side groups

    International Nuclear Information System (INIS)

    Lee, Bae Hoon; Song, Soo Chang; Lee, Young Moo; Sohn, Youn Soo

    2002-01-01

    Thermosensitive poly(organophosphazenes) bearing methoxy-poly(ethylene glycon) (MPEG) and alkylamine as substituents have been synthesized and characterized by elemental analysis, NMR spectroscopy, GPC, and DSC. All the polymers exhibited crystallinity, which was probably induced by the MPEG side chain of the polymers. All the polymers exhibited the lower critical solution temperature (LCSTs) in the range of 28 to 94 .deg. C depending on several factors such as mole ratio of the substituents, kinds of PEG and alkylamines. The higher content of MPEG and shorter chain length of alkylamines of the polymers afforded the higher LCST. The LCSTs of the polymers exhibited almost concentration-independent behavior in the range of 3-30 wt % of the polymers in aqueous solutions. The polymers showed the higher LCSTs in the acidic solutions than in the neutral and basic solutions. The ionic strength of the polymer solution affected the LCST,which decreased with increased NaCl concentration. The polymer bearing almost equimolar substituents with the -N-P-N unit has shown the LCST more sensitive to NaCl and pH than that with the -N-P-O- unit. The polymers were found to degrade in acidic solution but be very stable in alkali solution as well as in the buffer solution of pH 7.4

  12. Analysis of cold resistance and identification of SSR markers linked to cold resistance genes in Brassica rapa L.

    Science.gov (United States)

    Huang, Zhen; Zhang, Xuexian; Jiang, Shouhua; Qin, Mengfan; Zhao, Na; Lang, Lina; Liu, Yaping; Tian, Zhengshu; Liu, Xia; Wang, Yang; Zhang, Binbin; Xu, Aixia

    2017-06-01

    Currently, cold temperatures are one of the main factors threatening rapeseed production worldwide; thus, it is imperative to identify cold-resistant germplasm and to cultivate cold-resistant rapeseed varieties. In this study, the cold resistance of four Brassica rapa varieties was analyzed. The cold resistance of Longyou6 and Longyou7 was better than that of Tianyou2 and Tianyou4. Thus, an F 2 population derived from Longyou6 and Tianyou4 was used to study the correlation of cold resistance and physiological indexes. Our results showed that the degree of frost damage was related to the relative conductivity and MDA content (r1 = 0.558 and r2 = 0.447, respectively). In order to identify the markers related to cold resistance, 504 pairs of SSR (simple sequence repeats) primers were used to screen the two parents and F 2 population. Four and five SSR markers had highly significant positive correlation to relative conductivity and MDA, respectively. In addition, three of these SSR markers had a highly significant positive correlation to both of these two indexes. These three SSR markers were subsequently confirmed to be used to distinguish between cold-resistant and non-cold-resistant varieties. The results of this study will lay a solid foundation for the mapping of cold-resistant genes and molecular markers assisted selection for the cold-resistance.

  13. Colds and the Flu

    Science.gov (United States)

    ... disease (COPD). What medicines can I give my child? There is no cure for the cold or the flu, and antibiotics do not work against the viruses that cause colds and the flu. Pain relievers such as ...

  14. Cold neutron interferometry and its application. 2. Coherency and cold neutron spin interferometry

    International Nuclear Information System (INIS)

    Achiwa, Norio; Ebisawa, Toru

    1998-03-01

    The second workshop entitled 'Interference studies and cold neutron spin interferometry' was held on 10 and 11 March 1998 at KUR (Kyoto University Research Reactor Institute, Kumatori). Cold neutron spin interferometry is a new field. So it is very important for its development to learn the studies of X-ray and neutron optics which are rapidly developing with long history. In the workshop, the issues related to interference were reviewed such as experimental studies on cold neutron spin interferometry, theoretical and experimental approach on tunneling time, interference experiments by neutrons and its application, interference studies using synchrotron radiation, topics on silicon interferometry and quantum measurement problem and cold neutron interference experiment related to quantum measurement problem. The 8 of the presented papers are indexed individually. (J.P.N.)

  15. Transgenic tools to characterize neuronal properties of discrete populations of zebrafish neurons.

    Science.gov (United States)

    Satou, Chie; Kimura, Yukiko; Hirata, Hiromi; Suster, Maximiliano L; Kawakami, Koichi; Higashijima, Shin-ichi

    2013-09-01

    The developing nervous system consists of a variety of cell types. Transgenic animals expressing reporter genes in specific classes of neuronal cells are powerful tools for the study of neuronal network formation. We generated a wide variety of transgenic zebrafish that expressed reporter genes in specific classes of neurons or neuronal progenitors. These include lines in which neurons of specific neurotransmitter phenotypes expressed fluorescent proteins or Gal4, and lines in which specific subsets of the dorsal progenitor domain in the spinal cord expressed fluorescent proteins. Using these, we examined domain organization in the developing dorsal spinal cord, and found that there are six progenitor domains in zebrafish, which is similar to the domain organization in mice. We also systematically characterized neurotransmitter properties of the neurons that are produced from each domain. Given that reporter gene expressions occurs in a wide area of the nervous system in the lines generated, these transgenic fish should serve as powerful tools for the investigation of not only the neurons in the dorsal spinal cord but also neuronal structures and functions in many other regions of the nervous system.

  16. Cold moderators at ORNL

    International Nuclear Information System (INIS)

    Lucas, A. T.

    1997-09-01

    The Advanced Neutron Source (ANS) cold moderators were not an 'Oak Ridge first', but would have been the largest both physically and in terms of cold neutron flux. Two cold moderators were planned each 410 mm in diameter and containing about 30L of liquid deuterium. They were to be completely independent of each other. A modular system design was used to provide greater reliability and serviceability. When the ANS was terminated, upgrading of the resident High Flux Isotope Reactor (HFIR) was examined and an initial study was made into the feasibility of adding a cold source. Because the ANS design was modular, it was possible to use many identical design features. Sub-cooled liquid at 4 bar abs was initially chosen for the HFIR design concept, but this was subsequently changed to 15 bar abs to operate above the critical pressure. As in the ANS, the hydrogen will operate at a constant pressure throughout the temperature range and a completely closed loop with secondary containment was adopted. The heat load of 2 kW made the heat flux comparable with that of the ANS. Subsequent studies into the construction of cryogenic moderators for the proposed new Synchrotron Neutron source indicated that again many of the same design concepts could be used. By connecting the two cold sources together in series, the total heat load of 2 kW is very close to that of the HFIR allowing a very similar supercritical hydrogen system to be configured. The two hydrogen moderators of the SNS provide a comparable heat load to the HFIR moderator. It is subsequently planned to connect the two in series and operate from a single cold loop system, once again using supercritical hydrogen. The spallation source also provided an opportunity to re-examine a cold pellet solid methane moderator operating at 20K.

  17. Enhanced mechanical properties of thermosensitive chitosan hydrogel by silk fibers for cartilage tissue engineering

    International Nuclear Information System (INIS)

    Mirahmadi, Fereshteh; Tafazzoli-Shadpour, Mohammad; Shokrgozar, Mohammad Ali; Bonakdar, Shahin

    2013-01-01

    Articular cartilage has limited repair capability following traumatic injuries and current methods of treatment remain inefficient. Reconstructing cartilage provides a new way for cartilage repair and natural polymers are often used as scaffold because of their biocompatibility and biofunctionality. In this study, we added degummed chopped silk fibers and electrospun silk fibers to the thermosensitive chitosan/glycerophosphate hydrogels to reinforce two hydrogel constructs which were used as scaffold for hyaline cartilage regeneration. The gelation temperature and gelation time of hydrogel were analyzed by the rheometer and vial tilting method. Mechanical characterization was measured by uniaxial compression, indentation and dynamic mechanical analysis assay. Chondrocytes were then harvested from the knee joint of the New Zealand white rabbits and cultured in constructs. The cell proliferation, viability, production of glycosaminoglycans and collagen type II were assessed. The results showed that mechanical properties of the hydrogel were significantly enhanced when a hybrid with two layers of electrospun silk fibers was made. The results of GAG and collagen type II in cell-seeded scaffolds indicate support of the chondrogenic phenotype for chondrocytes with a significant increase in degummed silk fiber–hydrogel composite for GAG content and in two-layer electrospun fiber–hydrogel composite for Col II. It was concluded that these two modified scaffolds could be employed for cartilage tissue engineering. - Highlights: • Chitosan hydrogel composites fabricated by two forms of silk fiber • Silk fibers provide structural support for the hydrogel matrix. • The mechanical properties of hydrogel significantly improved by associating with silk. • Production of GAG and collagen type II was demonstrated within the scaffolds

  18. Enhanced mechanical properties of thermosensitive chitosan hydrogel by silk fibers for cartilage tissue engineering

    Energy Technology Data Exchange (ETDEWEB)

    Mirahmadi, Fereshteh [Faculty of Biomedical Engineering, Amirkabir University of Technology, Tehran (Iran, Islamic Republic of); National Cell Bank of Iran, Pasteur Institute of Iran, Tehran (Iran, Islamic Republic of); Tafazzoli-Shadpour, Mohammad, E-mail: Tafazoli@aut.ac.ir [Faculty of Biomedical Engineering, Amirkabir University of Technology, Tehran (Iran, Islamic Republic of); Shokrgozar, Mohammad Ali, E-mail: mashokrgozar@pasteur.ac.ir [National Cell Bank of Iran, Pasteur Institute of Iran, Tehran (Iran, Islamic Republic of); Bonakdar, Shahin [National Cell Bank of Iran, Pasteur Institute of Iran, Tehran (Iran, Islamic Republic of)

    2013-12-01

    Articular cartilage has limited repair capability following traumatic injuries and current methods of treatment remain inefficient. Reconstructing cartilage provides a new way for cartilage repair and natural polymers are often used as scaffold because of their biocompatibility and biofunctionality. In this study, we added degummed chopped silk fibers and electrospun silk fibers to the thermosensitive chitosan/glycerophosphate hydrogels to reinforce two hydrogel constructs which were used as scaffold for hyaline cartilage regeneration. The gelation temperature and gelation time of hydrogel were analyzed by the rheometer and vial tilting method. Mechanical characterization was measured by uniaxial compression, indentation and dynamic mechanical analysis assay. Chondrocytes were then harvested from the knee joint of the New Zealand white rabbits and cultured in constructs. The cell proliferation, viability, production of glycosaminoglycans and collagen type II were assessed. The results showed that mechanical properties of the hydrogel were significantly enhanced when a hybrid with two layers of electrospun silk fibers was made. The results of GAG and collagen type II in cell-seeded scaffolds indicate support of the chondrogenic phenotype for chondrocytes with a significant increase in degummed silk fiber–hydrogel composite for GAG content and in two-layer electrospun fiber–hydrogel composite for Col II. It was concluded that these two modified scaffolds could be employed for cartilage tissue engineering. - Highlights: • Chitosan hydrogel composites fabricated by two forms of silk fiber • Silk fibers provide structural support for the hydrogel matrix. • The mechanical properties of hydrogel significantly improved by associating with silk. • Production of GAG and collagen type II was demonstrated within the scaffolds.

  19. Morphine disinhibits glutamatergic input to VTA dopamine neurons and promotes dopamine neuron excitation.

    Science.gov (United States)

    Chen, Ming; Zhao, Yanfang; Yang, Hualan; Luan, Wenjie; Song, Jiaojiao; Cui, Dongyang; Dong, Yi; Lai, Bin; Ma, Lan; Zheng, Ping

    2015-07-24

    One reported mechanism for morphine activation of dopamine (DA) neurons of the ventral tegmental area (VTA) is the disinhibition model of VTA-DA neurons. Morphine inhibits GABA inhibitory neurons, which shifts the balance between inhibitory and excitatory input to VTA-DA neurons in favor of excitation and then leads to VTA-DA neuron excitation. However, it is not known whether morphine has an additional strengthening effect on excitatory input. Our results suggest that glutamatergic input to VTA-DA neurons is inhibited by GABAergic interneurons via GABAB receptors and that morphine promotes presynaptic glutamate release by removing this inhibition. We also studied the contribution of the morphine-induced disinhibitory effect on the presynaptic glutamate release to the overall excitatory effect of morphine on VTA-DA neurons and related behavior. Our results suggest that the disinhibitory action of morphine on presynaptic glutamate release might be the main mechanism for morphine-induced increase in VTA-DA neuron firing and related behaviors.

  20. IMPROVED, FAVORABLE FOR ENVIRONMENT POLYURETHANE COLD-BOX-PROCESS (COLD BOX «HUTTENES-ALBERTUS» .

    Directory of Open Access Journals (Sweden)

    A. Sergini

    2005-01-01

    Full Text Available The results of the laboratory and industrial investigations, the purpose of which is improvement of the classical Cold-box-process, i.e. the process of the slugs hardening in cold boxes, are presented.

  1. Neuronal medium that supports basic synaptic functions and activity of human neurons in vitro.

    Science.gov (United States)

    Bardy, Cedric; van den Hurk, Mark; Eames, Tameji; Marchand, Cynthia; Hernandez, Ruben V; Kellogg, Mariko; Gorris, Mark; Galet, Ben; Palomares, Vanessa; Brown, Joshua; Bang, Anne G; Mertens, Jerome; Böhnke, Lena; Boyer, Leah; Simon, Suzanne; Gage, Fred H

    2015-05-19

    Human cell reprogramming technologies offer access to live human neurons from patients and provide a new alternative for modeling neurological disorders in vitro. Neural electrical activity is the essence of nervous system function in vivo. Therefore, we examined neuronal activity in media widely used to culture neurons. We found that classic basal media, as well as serum, impair action potential generation and synaptic communication. To overcome this problem, we designed a new neuronal medium (BrainPhys basal + serum-free supplements) in which we adjusted the concentrations of inorganic salts, neuroactive amino acids, and energetic substrates. We then tested that this medium adequately supports neuronal activity and survival of human neurons in culture. Long-term exposure to this physiological medium also improved the proportion of neurons that were synaptically active. The medium was designed to culture human neurons but also proved adequate for rodent neurons. The improvement in BrainPhys basal medium to support neurophysiological activity is an important step toward reducing the gap between brain physiological conditions in vivo and neuronal models in vitro.

  2. NEURON and Python.

    Science.gov (United States)

    Hines, Michael L; Davison, Andrew P; Muller, Eilif

    2009-01-01

    The NEURON simulation program now allows Python to be used, alone or in combination with NEURON's traditional Hoc interpreter. Adding Python to NEURON has the immediate benefit of making available a very extensive suite of analysis tools written for engineering and science. It also catalyzes NEURON software development by offering users a modern programming tool that is recognized for its flexibility and power to create and maintain complex programs. At the same time, nothing is lost because all existing models written in Hoc, including graphical user interface tools, continue to work without change and are also available within the Python context. An example of the benefits of Python availability is the use of the xml module in implementing NEURON's Import3D and CellBuild tools to read MorphML and NeuroML model specifications.

  3. Cold medicines and children

    Science.gov (United States)

    ... ingredient. Avoid giving more than one OTC cold medicine to your child. It may cause an overdose with severe side ... the dosage instructions strictly while giving an OTC medicine to your child. When giving OTC cold medicines to your child: ...

  4. On cold spots in tumor subvolumes

    International Nuclear Information System (INIS)

    Tome, Wolfgang A.; Fowler, Jack F.

    2002-01-01

    Losses in tumor control are estimated for cold spots of various 'sizes' and degrees of 'cold dose'. This question is important in the context of intensity modulated radiotherapy where differential dose-volume histograms (DVHs) for targets that abut a critical structure often exhibit a cold dose tail. This can be detrimental to tumor control probability (TCP) for fractions of cold volumes even as small as 1%, if the cold dose is lower than the prescribed dose by substantially more than 10%. The Niemierko-Goitein linear-quadratic algorithm with γ 50 slope 1-3 was used to study the effect of cold spots of various degrees (dose deficit below the prescription dose) and size (fractional volume of the cold dose). A two-bin model DVH has been constructed in which the cold dose bin is allowed to vary from a dose deficit of 1%-50% below prescription dose and to have volumes varying from 1% to 90%. In order to study and quantify the effect of a small volume of cold dose on TCP and effective uniform dose (EUD), a four-bin DVH model has been constructed in which the lowest dose bin, which has a fractional volume of 1%, is allowed to vary from 10% to 45% dose deficit below prescription dose. The highest dose bin represents a simultaneous boost. For fixed size of the cold spot the calculated values of TCP decreased rapidly with increasing degrees of cold dose for any size of the cold spot, even as small as 1% fractional volume. For the four-subvolume model, in which the highest dose bin has a fractional volume of 80% and is set at a boost dose of 10% above prescription dose, it is found that the loss in TCP and EUD is moderate as long as the cold 1% subvolume has a deficit less than approximately 20%. However, as the dose deficit in the 1% subvolume bin increases further it drives TCP and EUD rapidly down and can lead to a serious loss in TCP and EUD. Since a dose deficit to a 1% volume of the target that is larger than 20% of the prescription dose may lead to serious loss of

  5. A transcription factor for cold sensation!

    Directory of Open Access Journals (Sweden)

    Milbrandt Jeffrey

    2005-03-01

    Full Text Available Abstract The ability to feel hot and cold is critical for animals and human beings to survive in the natural environment. Unlike other sensations, the physiology of cold sensation is mostly unknown. In the present study, we use genetically modified mice that do not express nerve growth factor-inducible B (NGFIB to investigate the possible role of NGFIB in cold sensation. We found that genetic deletion of NGFIB selectively affected behavioral responses to cold stimuli while behavioral responses to noxious heat or mechanical stimuli were normal. Furthermore, behavioral responses remained reduced or blocked in NGFIB knockout mice even after repetitive application of cold stimuli. Our results provide strong evidence that the first transcription factor NGFIB determines the ability of animals to respond to cold stimulation.

  6. BigNeuron: Large-scale 3D Neuron Reconstruction from Optical Microscopy Images

    OpenAIRE

    Peng, Hanchuan; Hawrylycz, Michael; Roskams, Jane; Hill, Sean; Spruston, Nelson; Meijering, Erik; Ascoli, Giorgio A.

    2015-01-01

    textabstractUnderstanding the structure of single neurons is critical for understanding how they function within neural circuits. BigNeuron is a new community effort that combines modern bioimaging informatics, recent leaps in labeling and microscopy, and the widely recognized need for openness and standardization to provide a community resource for automated reconstruction of dendritic and axonal morphology of single neurons. Understanding the structure of single neurons is critical for unde...

  7. Optogenetic identification of hypothalamic orexin neuron projections to paraventricular spinally projecting neurons.

    Science.gov (United States)

    Dergacheva, Olga; Yamanaka, Akihiro; Schwartz, Alan R; Polotsky, Vsevolod Y; Mendelowitz, David

    2017-04-01

    Orexin neurons, and activation of orexin receptors, are generally thought to be sympathoexcitatory; however, the functional connectivity between orexin neurons and a likely sympathetic target, the hypothalamic spinally projecting neurons (SPNs) in the paraventricular nucleus of the hypothalamus (PVN) has not been established. To test the hypothesis that orexin neurons project directly to SPNs in the PVN, channelrhodopsin-2 (ChR2) was selectively expressed in orexin neurons to enable photoactivation of ChR2-expressing fibers while examining evoked postsynaptic currents in SPNs in rat hypothalamic slices. Selective photoactivation of orexin fibers elicited short-latency postsynaptic currents in all SPNs tested ( n = 34). These light-triggered responses were heterogeneous, with a majority being excitatory glutamatergic responses (59%) and a minority of inhibitory GABAergic (35%) and mixed glutamatergic and GABAergic currents (6%). Both glutamatergic and GABAergic responses were present in the presence of tetrodotoxin and 4-aminopyridine, suggesting a monosynaptic connection between orexin neurons and SPNs. In addition to generating postsynaptic responses, photostimulation facilitated action potential firing in SPNs (current clamp configuration). Glutamatergic, but not GABAergic, postsynaptic currents were diminished by application of the orexin receptor antagonist almorexant, indicating orexin release facilitates glutamatergic neurotransmission in this pathway. This work identifies a neuronal circuit by which orexin neurons likely exert sympathoexcitatory control of cardiovascular function. NEW & NOTEWORTHY This is the first study to establish, using innovative optogenetic approaches in a transgenic rat model, that there are robust heterogeneous projections from orexin neurons to paraventricular spinally projecting neurons, including excitatory glutamatergic and inhibitory GABAergic neurotransmission. Endogenous orexin release modulates glutamatergic, but not

  8. Essential roles of mitochondrial depolarization in neuron loss through microglial activation and attraction toward neurons.

    Science.gov (United States)

    Nam, Min-Kyung; Shin, Hyun-Ah; Han, Ji-Hye; Park, Dae-Wook; Rhim, Hyangshuk

    2013-04-10

    As life spans increased, neurodegenerative disorders that affect aging populations have also increased. Progressive neuronal loss in specific brain regions is the most common cause of neurodegenerative disease; however, key determinants mediating neuron loss are not fully understood. Using a model of mitochondrial membrane potential (ΔΨm) loss, we found only 25% cell loss in SH-SY5Y (SH) neuronal mono-cultures, but interestingly, 85% neuronal loss occurred when neurons were co-cultured with BV2 microglia. SH neurons overexpressing uncoupling protein 2 exhibited an increase in neuron-microglia interactions, which represent an early step in microglial phagocytosis of neurons. This result indicates that ΔΨm loss in SH neurons is an important contributor to recruitment of BV2 microglia. Notably, we show that ΔΨm loss in BV2 microglia plays a crucial role in microglial activation and phagocytosis of damaged SH neurons. Thus, our study demonstrates that ΔΨm loss in both neurons and microglia is a critical determinant of neuron loss. These findings also offer new insights into neuroimmunological and bioenergetical aspects of neurodegenerative disease. Copyright © 2013 Elsevier B.V. All rights reserved.

  9. Endorphinic neurons are contacting the tuberoinfundibular dopaminergic neurons in the rat brain

    International Nuclear Information System (INIS)

    Morel, G.; Pelletier, G.

    1986-01-01

    The anatomical relationships between endorphinic neurons and dopaminergic neurons were evaluated in the rat hypothalamus using a combination of immunocytochemistry and autoradiography. In the arcuate nucleus, endorphinic endings were seen making contacts with dopaminergic cell bodies and dendrites. No synapsis could be observed at the sites of contacts. These results strongly suggest that the endorphinic neurons are directly acting on dopaminergic neurons to modify the release of dopamine into the pituitary portal system

  10. Liquid metal cold trap

    International Nuclear Information System (INIS)

    Hundal, R.

    1976-01-01

    A cold trap assembly for removing impurities from a liquid metal is described. A hole between the incoming impure liquid metal and purified outgoing liquid metal acts as a continuous bleed means and thus prevents the accumulation of cover gases within the cold trap assembly

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

    Science.gov (United States)

    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.

  12. Cold-formed steel design

    CERN Document Server

    Yu, Wei-Wen

    2010-01-01

    The definitive text in the field, thoroughly updated and expanded Hailed by professionals around the world as the definitive text on the subject, Cold-Formed Steel Design is an indispensable resource for all who design for and work with cold-formed steel. No other book provides such exhaustive coverage of both the theory and practice of cold-formed steel construction. Updated and expanded to reflect all the important developments that have occurred in the field over the past decade, this Fourth Edition of the classic text provides you with more of the detailed, up-to-the-minute techni

  13. Workshop on cold-blanket research

    International Nuclear Information System (INIS)

    1977-05-01

    The objective of the workshop was to identify and discuss cold-plasma blanket systems. In order to minimize the bombardment of the walls by hot neutrals the plasma should be impermeable. This requires a density edge-thickness product of nΔ > 10 15 cm -2 . An impermeable cold plasma-gas blanket surrounding a hot plasma core reduces the plasma wall/limiter interaction. Accumulation of impurities in this blanket can be expected. Fuelling from a blanket may be possible as shown by experimental results, though not fully explained by classical transport of neutrals. Refuelling of a reacting plasma had to be ensured by inward diffusion. Experimental studies of a cold impermeable plasma have been done on the tokamak-like Ringboog device. Simulation calculations for the next generation of large tokamaks using a particular transport model, indicate that the plasma edge profile can be controlled to reduce the production of sputtered impurities to an acceptable level. Impurity control requires a small fraction of the radial space to accomodate the cold-plasma layer. The problem of exhaust is, however, more complicated. If the cold-blanket scheme works as predicted in the model calculations, then α-particles generated by fusion will be transported to the cold outside layer. The Communities' experimental programme of research has been discussed in terms of the tokamaks which are available and planned. Two options present themselves for the continuation of cold-blanket research

  14. Catching a Cold When It's Warm

    Science.gov (United States)

    ... Print this issue Catching a Cold When It’s Warm What’s the Deal with Summertime Sniffles? En español ... more unfair than catching a cold when it’s warm? How can cold symptoms arise when it’s not ...

  15. Neuronal synchrony: peculiarity and generality.

    Science.gov (United States)

    Nowotny, Thomas; Huerta, Ramon; Rabinovich, Mikhail I

    2008-09-01

    Synchronization in neuronal systems is a new and intriguing application of dynamical systems theory. Why are neuronal systems different as a subject for synchronization? (1) Neurons in themselves are multidimensional nonlinear systems that are able to exhibit a wide variety of different activity patterns. Their "dynamical repertoire" includes regular or chaotic spiking, regular or chaotic bursting, multistability, and complex transient regimes. (2) Usually, neuronal oscillations are the result of the cooperative activity of many synaptically connected neurons (a neuronal circuit). Thus, it is necessary to consider synchronization between different neuronal circuits as well. (3) The synapses that implement the coupling between neurons are also dynamical elements and their intrinsic dynamics influences the process of synchronization or entrainment significantly. In this review we will focus on four new problems: (i) the synchronization in minimal neuronal networks with plastic synapses (synchronization with activity dependent coupling), (ii) synchronization of bursts that are generated by a group of nonsymmetrically coupled inhibitory neurons (heteroclinic synchronization), (iii) the coordination of activities of two coupled neuronal networks (partial synchronization of small composite structures), and (iv) coarse grained synchronization in larger systems (synchronization on a mesoscopic scale). (c) 2008 American Institute of Physics.

  16. Discrimination of communication vocalizations by single neurons and groups of neurons in the auditory midbrain.

    Science.gov (United States)

    Schneider, David M; Woolley, Sarah M N

    2010-06-01

    Many social animals including songbirds use communication vocalizations for individual recognition. The perception of vocalizations depends on the encoding of complex sounds by neurons in the ascending auditory system, each of which is tuned to a particular subset of acoustic features. Here, we examined how well the responses of single auditory neurons could be used to discriminate among bird songs and we compared discriminability to spectrotemporal tuning. We then used biologically realistic models of pooled neural responses to test whether the responses of groups of neurons discriminated among songs better than the responses of single neurons and whether discrimination by groups of neurons was related to spectrotemporal tuning and trial-to-trial response variability. The responses of single auditory midbrain neurons could be used to discriminate among vocalizations with a wide range of abilities, ranging from chance to 100%. The ability to discriminate among songs using single neuron responses was not correlated with spectrotemporal tuning. Pooling the responses of pairs of neurons generally led to better discrimination than the average of the two inputs and the most discriminating input. Pooling the responses of three to five single neurons continued to improve neural discrimination. The increase in discriminability was largest for groups of neurons with similar spectrotemporal tuning. Further, we found that groups of neurons with correlated spike trains achieved the largest gains in discriminability. We simulated neurons with varying levels of temporal precision and measured the discriminability of responses from single simulated neurons and groups of simulated neurons. Simulated neurons with biologically observed levels of temporal precision benefited more from pooling correlated inputs than did neurons with highly precise or imprecise spike trains. These findings suggest that pooling correlated neural responses with the levels of precision observed in the

  17. Large reptiles and cold temperatures: Do extreme cold spells set distributional limits for tropical reptiles in Florida?

    Science.gov (United States)

    Mazzotti, Frank J.; Cherkiss, Michael S.; Parry, Mark; Beauchamp, Jeff; Rochford, Mike; Smith, Brian J.; Hart, Kristen M.; Brandt, Laura A.

    2016-01-01

    Distributional limits of many tropical species in Florida are ultimately determined by tolerance to low temperature. An unprecedented cold spell during 2–11 January 2010, in South Florida provided an opportunity to compare the responses of tropical American crocodiles with warm-temperate American alligators and to compare the responses of nonnative Burmese pythons with native warm-temperate snakes exposed to prolonged cold temperatures. After the January 2010 cold spell, a record number of American crocodiles (n = 151) and Burmese pythons (n = 36) were found dead. In contrast, no American alligators and no native snakes were found dead. American alligators and American crocodiles behaved differently during the cold spell. American alligators stopped basking and retreated to warmer water. American crocodiles apparently continued to bask during extreme cold temperatures resulting in lethal body temperatures. The mortality of Burmese pythons compared to the absence of mortality for native snakes suggests that the current population of Burmese pythons in the Everglades is less tolerant of cold temperatures than native snakes. Burmese pythons introduced from other parts of their native range may be more tolerant of cold temperatures. We documented the direct effects of cold temperatures on crocodiles and pythons; however, evidence of long-term effects of cold temperature on their populations within their established ranges remains lacking. Mortality of crocodiles and pythons outside of their current established range may be more important in setting distributional limits.

  18. Dual-functional transdermal drug delivery system with controllable drug loading based on thermosensitive poloxamer hydrogel for atopic dermatitis treatment

    Science.gov (United States)

    Wang, Wenyi; Wat, Elaine; Hui, Patrick C. L.; Chan, Ben; Ng, Frency S. F.; Kan, Chi-Wai; Wang, Xiaowen; Hu, Huawen; Wong, Eric C. W.; Lau, Clara B. S.; Leung, Ping-Chung

    2016-04-01

    The treatment of atopic dermatitis (AD) has long been viewed as a problematic issue by the medical profession. Although a wide variety of complementary therapies have been introduced, they fail to combine the skin moisturizing and drug supply for AD patients. This study reports the development of a thermo-sensitive Poloxamer 407/Carboxymethyl cellulose sodium (P407/CMCs) composite hydrogel formulation with twin functions of moisture and drug supply for AD treatment. It was found that the presence of CMCs can appreciably improve the physical properties of P407 hydrogel, which makes it more suitable for tailored drug loading. The fabricated P407/CMCs composite hydrogel was also characterized in terms of surface morphology by field emission scanning electron microscopy (FE-SEM), rheological properties by a rheometer, release profile in vitro by dialysis method and cytotoxicity test. More importantly, the findings from transdermal drug delivery behavior revealed that P407/CMCs showed desirable percutaneous performance. Additionally, analysis of cytotoxicity test suggested that P407/CMCs composite hydrogel is a high-security therapy for clinical trials and thus exhibits a promising way to treat AD with skin moisturizing and medication.

  19. Spinal cord: motor neuron diseases.

    Science.gov (United States)

    Rezania, Kourosh; Roos, Raymond P

    2013-02-01

    Spinal cord motor neuron diseases affect lower motor neurons in the ventral horn. This article focuses on the most common spinal cord motor neuron disease, amyotrophic lateral sclerosis, which also affects upper motor neurons. Also discussed are other motor neuron diseases that only affect the lower motor neurons. Despite the identification of several genes associated with familial amyotrophic lateral sclerosis, the pathogenesis of this complex disease remains elusive. Copyright © 2013 Elsevier Inc. All rights reserved.

  20. Tip model of cold fission

    International Nuclear Information System (INIS)

    Goennenwein, F.; Boersig, B.

    1991-01-01

    Cold fission is defined to be the limiting case of nuclear fission where virtually all of the available energy is converted into the total kinetic energy of the fragments. The fragments have, therefore, to be born in or at least close to their respective ground states. Starting from the viewpoint that cold fission corresponds to most compact scission configurations, energy constraints have been exploited to calculate minimum tip distances between the two nascent fragments in binary fission. Crucial input parameters to this tip model of cold fission are the ground-state deformations of fragment nuclei. It is shown that the minimum tip distances being compatible with energy conservation vary strongly with both the mass and charge fragmentation of the fission prone nucleus. The tip distances refer to nuclei with equivalent sharp surfaces. In keeping with the size of the surface width of leptodermous nuclei, only configurations where the tip distances are smaller than a few fm may be considered as valid scission configurations. From a comparison with experimental data on cold fission this critical tip distance appears to be 3.0 fm for the model parameters chosen. Whenever the model calculation yields tip distances being smaller than the critical value, a necessary condition for attaining cold fission is considered to be fulfilled. It is shown that this criterion allows to understand in fair agreement with experiment which mass fragmentations are susceptible to lead to cold fission and which fragment-charge divisions are the most favored in each isobaric mass chain. Being based merely on energy arguments, the model cannot aim at predicting fragment yields in cold fission. However, the tip model proposed appears well suited to delineate the phase space where cold fission phenomena may come into sight. (orig.)

  1. Cold moderators for pulsed neutron sources

    International Nuclear Information System (INIS)

    Carpenter, J.M.

    1990-01-01

    This paper reviews cold moderators in pulsed neutron sources and provides details of the performance of different cold moderator materials and configurations. Analytical forms are presented which describe wavelength spectra and emission time distributions. Several types of cooling arrangements used in pulsed source moderators are described. Choices of materials are surveyed. The author examines some of the radiation damage effects in cold moderators, including the phenomenon of ''burping'' in irradiated cold solid methane. 9 refs., 15 figs., 4 tabs

  2. A transcription factor for cold sensation!

    OpenAIRE

    Kim, Susan J; Qu, Zhican; Milbrandt, Jeffrey; Zhuo, Min

    2005-01-01

    Abstract The ability to feel hot and cold is critical for animals and human beings to survive in the natural environment. Unlike other sensations, the physiology of cold sensation is mostly unknown. In the present study, we use genetically modified mice that do not express nerve growth factor-inducible B (NGFIB) to investigate the possible role of NGFIB in cold sensation. We found that genetic deletion of NGFIB selectively affected behavioral responses to cold stimuli while behavioral respons...

  3. International workshop on cold neutron sources

    Energy Technology Data Exchange (ETDEWEB)

    Russell, G.J.; West, C.D. (comps.) (Los Alamos National Lab., NM (United States))

    1991-08-01

    The first meeting devoted to cold neutron sources was held at the Los Alamos National Laboratory on March 5--8, 1990. Cosponsored by Los Alamos and Oak Ridge National Laboratories, the meeting was organized as an International Workshop on Cold Neutron Sources and brought together experts in the field of cold-neutron-source design for reactors and spallation sources. Eighty-four people from seven countries attended. Because the meeting was the first of its kind in over forty years, much time was spent acquainting participants with past and planned activities at reactor and spallation facilities worldwide. As a result, the meeting had more of a conference flavor than one of a workshop. The general topics covered at the workshop included: Criteria for cold source design; neutronic predictions and performance; energy deposition and removal; engineering design, fabrication, and operation; material properties; radiation damage; instrumentation; safety; existing cold sources; and future cold sources.

  4. International workshop on cold neutron sources

    International Nuclear Information System (INIS)

    Russell, G.J.; West, C.D.

    1991-08-01

    The first meeting devoted to cold neutron sources was held at the Los Alamos National Laboratory on March 5--8, 1990. Cosponsored by Los Alamos and Oak Ridge National Laboratories, the meeting was organized as an International Workshop on Cold Neutron Sources and brought together experts in the field of cold-neutron-source design for reactors and spallation sources. Eighty-four people from seven countries attended. Because the meeting was the first of its kind in over forty years, much time was spent acquainting participants with past and planned activities at reactor and spallation facilities worldwide. As a result, the meeting had more of a conference flavor than one of a workshop. The general topics covered at the workshop included: Criteria for cold source design; neutronic predictions and performance; energy deposition and removal; engineering design, fabrication, and operation; material properties; radiation damage; instrumentation; safety; existing cold sources; and future cold sources

  5. Cold trap disposed within a tank

    International Nuclear Information System (INIS)

    Kanbe, Mitsuru.

    1983-01-01

    Purpose: To improve the reliability and the durability of cold traps by simplifying the structure and recycling liquid metals without using electromagnetic pumps. Constitution: The reactor container is partitioned by an intermediate container enhousing primary recycling pumps and cold traps. The inlet and the exit for the liquid metal of each cold trap are opened to the outside and the inside of the intermediate container respectively. In such a structure, the pressure difference between the inside and the outside of the intermediate container is exerted on the cold traps due to the exhaust pressure of the recycling pumps in which the liquid metal flowing into the cold traps is purified through filters, cooled and then discharged from the exit to the cold plenum. In this way, liquid metal can be recycled without using an electromagnetic pump whose reliability has not yet been established. (Kamimura, M.)

  6. Parkin Mutations Reduce the Complexity of Neuronal Processes in iPSC-derived Human Neurons

    Science.gov (United States)

    Ren, Yong; Jiang, Houbo; Hu, Zhixing; Fan, Kevin; Wang, Jun; Janoschka, Stephen; Wang, Xiaomin; Ge, Shaoyu; Feng, Jian

    2015-01-01

    Parkinson’s disease (PD) is characterized by the degeneration of nigral dopaminergic (DA) neurons and non-DA neurons in many parts of the brain. Mutations of parkin, an E3 ubiquitin ligase that strongly binds to microtubules, are the most frequent cause of recessively inherited Parkinson’s disease. The lack of robust PD phenotype in parkin knockout mice suggests a unique vulnerability of human neurons to parkin mutations. Here, we show that the complexity of neuronal processes as measured by total neurite length, number of terminals, number of branch points and Sholl analysis, was greatly reduced in induced pluripotent stem cell (iPSC)-derived TH+ or TH− neurons from PD patients with parkin mutations. Consistent with these, microtubule stability was significantly decreased by parkin mutations in iPSC-derived neurons. Overexpression of parkin, but not its PD-linked mutant nor GFP, restored the complexity of neuronal processes and the stability of microtubules. Consistent with these, the microtubule-depolymerizing agent colchicine mimicked the effect of parkin mutations by decreasing neurite length and complexity in control neurons while the microtubule-stabilizing drug taxol mimicked the effect of parkin overexpression by enhancing the morphology of parkin-deficient neurons. The results suggest that parkin maintains the morphological complexity of human neurons by stabilizing microtubules. PMID:25332110

  7. Cold War Paradigms and the Post-Cold War High School History Curriculum.

    Science.gov (United States)

    McAninch, Stuart A.

    1995-01-01

    Discusses how Cold War ideological models provide a way to examine the U.S. role in world affairs. Discusses and compares on the writings of Paul Gagnon and Noam Chomsky on this topic. Concludes that students should stand outside both models to develop a meaningful perspective on the U.S. role during the Cold War. (CFR)

  8. Dence Cold Matter

    Directory of Open Access Journals (Sweden)

    Stavinskiy Alexey

    2014-04-01

    Full Text Available Possible way to create dense cold baryonic matter in the laboratory is discussed. The density of this matter is comparable or even larger than the density of neutron star core. The properties of this matter can be controlled by trigger conditions. Experimental program for the study of properties of dense cold matter for light and heavy ion collisions at initial energy range √sNN~2-3GeV is proposed..

  9. Metabolic reprogramming during neuronal differentiation from aerobic glycolysis to neuronal oxidative phosphorylation.

    Science.gov (United States)

    Zheng, Xinde; Boyer, Leah; Jin, Mingji; Mertens, Jerome; Kim, Yongsung; Ma, Li; Ma, Li; Hamm, Michael; Gage, Fred H; Hunter, Tony

    2016-06-10

    How metabolism is reprogrammed during neuronal differentiation is unknown. We found that the loss of hexokinase (HK2) and lactate dehydrogenase (LDHA) expression, together with a switch in pyruvate kinase gene splicing from PKM2 to PKM1, marks the transition from aerobic glycolysis in neural progenitor cells (NPC) to neuronal oxidative phosphorylation. The protein levels of c-MYC and N-MYC, transcriptional activators of the HK2 and LDHA genes, decrease dramatically. Constitutive expression of HK2 and LDHA during differentiation leads to neuronal cell death, indicating that the shut-off aerobic glycolysis is essential for neuronal survival. The metabolic regulators PGC-1α and ERRγ increase significantly upon neuronal differentiation to sustain the transcription of metabolic and mitochondrial genes, whose levels are unchanged compared to NPCs, revealing distinct transcriptional regulation of metabolic genes in the proliferation and post-mitotic differentiation states. Mitochondrial mass increases proportionally with neuronal mass growth, indicating an unknown mechanism linking mitochondrial biogenesis to cell size.

  10. Protocol for culturing low density pure rat hippocampal neurons supported by mature mixed neuron cultures.

    Science.gov (United States)

    Yang, Qian; Ke, Yini; Luo, Jianhong; Tang, Yang

    2017-02-01

    primary hippocampal neuron cultures allow for subcellular morphological dissection, easy access to drug treatment and electrophysiology analysis of individual neurons, and is therefore an ideal model for the study of neuron physiology. While neuron and glia mixed cultures are relatively easy to prepare, pure neurons are particular hard to culture at low densities which are suitable for morphology studies. This may be due to a lack of neurotrophic factors such as brain derived neurotrophic factor (BDNF), neurotrophin-3 (NT3) and Glial cell line-derived neurotrophic factor (GDNF). In this study we used a two step protocol in which neuron-glia mixed cultures were initially prepared for maturation to support the growth of young neurons plated at very low densities. Our protocol showed that neurotrophic support resulted in physiologically functional hippocampal neurons with larger cell body, increased neurite length and decreased branching and complexity compared to cultures prepared using a conventional method. Our protocol provides a novel way to culture highly uniformed hippocampal neurons for acquiring high quality, neuron based data. Copyright © 2016 Elsevier B.V. All rights reserved.

  11. Body temperature and cold sensation during and following exercise under temperate room conditions in cold-sensitive young trained females.

    Science.gov (United States)

    Fujii, Naoto; Aoki-Murakami, Erii; Tsuji, Bun; Kenny, Glen P; Nagashima, Kei; Kondo, Narihiko; Nishiyasu, Takeshi

    2017-11-01

    We evaluated cold sensation at rest and in response to exercise-induced changes in core and skin temperatures in cold-sensitive exercise trained females. Fifty-eight trained young females were screened by a questionnaire, selecting cold-sensitive (Cold-sensitive, n  = 7) and non-cold-sensitive (Control, n  = 7) individuals. Participants rested in a room at 29.5°C for ~100 min after which ambient temperature was reduced to 23.5°C where they remained resting for 60 min. Participants then performed 30-min of moderate intensity cycling (50% peak oxygen uptake) followed by a 60-min recovery. Core and mean skin temperatures and cold sensation over the whole-body and extremities (fingers and toes) were assessed throughout. Resting core temperature was lower in the Cold-sensitive relative to Control group (36.4 ± 0.3 vs. 36.7 ± 0.2°C). Core temperature increased to similar levels at end-exercise (~37.2°C) and gradually returned to near preexercise rest levels at the end of recovery (>36.6°C). Whole-body cold sensation was greater in the Cold-sensitive relative to Control group during resting at a room temperature of 23.5°C only without a difference in mean skin temperature between groups. In contrast, cold sensation of the extremities was greater in the Cold-sensitive group prior to, during and following exercise albeit this was not paralleled by differences in mean extremity skin temperature. We show that young trained females who are sensitive to cold exhibit augmented whole-body cold sensation during rest under temperate ambient conditions. However, this response is diminished during and following exercise. In contrast, cold sensation of extremities is augmented during resting that persists during and following exercise. © 2017 The Authors. Physiological Reports published by Wiley Periodicals, Inc. on behalf of The Physiological Society and the American Physiological Society.

  12. Integrated method of thermosensitive triblock copolymer-salt aqueous two phase extraction and dialysis membrane separation for purification of lycium barbarum polysaccharide.

    Science.gov (United States)

    Wang, Yun; Hu, Xiaowei; Han, Juan; Ni, Liang; Tang, Xu; Hu, Yutao; Chen, Tong

    2016-03-01

    A polymer-salt aqueous two-phase system (ATPS) consisting of thermosensitive copolymer ethylene-oxide-b-propylene-oxide-b-ethylene-oxide (EOPOEO) and NaH2PO4 was employed in deproteinization for lycium barbarum polysaccharide (LBP). The effects of salt type and concentration, EOPOEO concentration, amount of crude LBP solution and temperature were studied. In the primary extraction process, LBP was preferentially partitioned to the bottom (salt-rich) phase with high recovery ratio of 96.3%, while 94.4% of impurity protein was removed to the top (EOPOEO-rich) phase. Moreover, the majority of pigments could be discarded to top phase. After phase-separation, the LBP in the bottom phase was further purified by dialysis membrane to remove salt and other small molecular impurities. The purity of LBP was enhanced to 64%. Additionally, the FT-IR spectrum was used to identify LBP. EOPOEO was recovered by a temperature-induced separation, and reused in a new ATPS. An ideal extraction and recycle result were achieved. Copyright © 2015 Elsevier Ltd. All rights reserved.

  13. Grafting of allylimidazole and n-vinylcaprolactam as a thermosensitive polymer onto magnetic nano-particles for the extraction and determination of celecoxib in biological samples.

    Science.gov (United States)

    Morovati, Atefeh; Ahmad Panahi, Homayon; Yazdani, Farzaneh

    2016-11-20

    In this research, a novel method is reported for the surface grafting of n-vinylcaprolactam as a thermosensitive agent and allylimidazole with affinity toward celecoxib onto magnetic nano-particles. The grafted nano-particles were characterized by Fourier transform infrared spectroscopy, elemental analysis, and thermogravimetric analysis. The surface morphology was studied using Scanning Electron Microscopy. The resulting grafted nano-particles were used for the determination of trace celecoxib in biological human fluids and pharmaceutical samples. The profile of celecoxib uptake by the modified magnetic nano-particles indicated good accessibility of the active sites in the grafted copolymer. It was found that the adsorption behavior could be fitted by the Langmuir adsorption isotherm model. Solid phase extraction for biological fluids such as urine and serum were investigated. In this study, urine extraction recovery of more than 95% was obtained. Copyright © 2016 Elsevier B.V. All rights reserved.

  14. Imaging with cold neutrons

    International Nuclear Information System (INIS)

    Lehmann, E.H.; Kaestner, A.; Josic, L.; Hartmann, S.; Mannes, D.

    2011-01-01

    Neutrons for imaging purposes are provided mainly from thermal beam lines at suitable facilities around the world. The access to cold neutrons is presently limited to very few places only. However, many challenging options for imaging with cold neutrons have been found out, given by the interaction behavior of the observed materials with neutrons in the cold energy range (3-10 A). For absorbing materials, the interaction probability increases proportionally with the wavelength with the consequence of more contrast but less transmission with cold neutrons. Many materials are predominantly scattering neutrons, in particular most of crystalline structural materials. In these cases, cold neutrons play an important role by covering the energy range of the most important Bragg edges given by the lattice planes of the crystallites. This particular behavior can be used for at least two important aspects-choosing the right energy of the initial beam enables to have a material more or less transparent, and a direct macroscopic visualization of the crystalline structure and its change in a manufacturing process. Since 2006, PSI operates its second beam line for neutron imaging, where cold neutrons are provided from a liquid deuterium cold source (operated at 25 K). It has been designed to cover the most current aspects in neutron imaging research with the help of high flexibility. This has been done with changeable inlet apertures, a turbine based velocity selector, two beam positions and variable detector systems, satisfying the demands of the individual investigation. The most important detection system was found to be a micro-tomography system that enables studies in the presently best spatial resolution. In this case, the high contrast from the sample interaction process and the high detection probability for the cold neutrons combines in an ideal combination for the best possible performance. Recently, it was found out that the energy selective studies might become a

  15. The PM1 neurons, movement sensitive centrifugal visual brain neurons in the locust: anatomy, physiology, and modulation by identified octopaminergic neurons.

    Science.gov (United States)

    Stern, Michael

    2009-02-01

    The locust's optic lobe contains a system of wide-field, multimodal, centrifugal neurons. Two of these cells, the protocerebrum-medulla-neurons PM4a and b, are octopaminergic. This paper describes a second pair of large centrifugal neurons (the protocerebrum-medulla-neurons PM1a and PM1b) from the brain of Locusta migratoria based on intracellular cobalt fills, electrophysiology, and immunocytochemistry. They originate and arborise in the central brain and send processes into the medulla of the optic lobe. Double intracellular recording from the same cell suggests input in the central brain and output in the optic lobe. The neurons show immunoreactivity to gamma-amino-butyric acid and its synthesising enzyme, glutamate decarboxylase. The PM1 cells are movement sensitive and show habituation to repeated visual stimulation. Bath application of octopamine causes the response to dishabituate. A very similar effect is produced by electrical stimulation of one of an octopaminergic PM4 neuron. This effect can be blocked by application of the octopamine antagonists, mianserin and phentolamine. This readily accessible system of four wide-field neurons provides a system suitable for the investigation of octopaminergic effects on the visual system at the cellular level.

  16. Cold-water acclimation does not modify whole-body fluid regulation during subsequent cold-water immersion.

    Science.gov (United States)

    Stocks, J M; Patterson, M J; Hyde, D E; Jenkins, A B; Mittleman, K D; Taylor, N A S

    2004-06-01

    We investigated the impact of cold-water acclimation on whole-body fluid regulation using tracer-dilution methods to differentiate between the intracellular and extracellular fluid compartments. Seven euhydrated males [age 24.7 (8.7) years, mass 74.4 (6.4) kg, height 176.8 (7.8) cm, sum of eight skinfolds 107.4 (20.4) mm; mean (SD)] participated in a 14-day cold-water acclimation protocol, with 60-min resting cold-water stress tests [CWST; 18.1 (0.1) degrees C] on days 1, 8 and 15, and 90-min resting cold-water immersions [18.4 (0.4) degrees C] on intervening days. Subjects were immersed to the 4th intercostal space. Intracellular and extracellular fluid compartments, and plasma protein, electrolyte and hormone concentrations were investigated. During the first CWST, the intracellular fluid (5.5%) and plasma volumes were reduced (6.1%), while the interstitial fluid volume was simultaneously expanded (5.4%). This pattern was replicated on days 8 and 15, but did not differ significantly among test days. Acclimation did not produce significant changes in the pre-immersion distribution of total body water, or changes in plasma osmolality, total protein, electrolyte, atrial natriuretic peptide or aldosterone concentrations. Furthermore, a 14-day cold-water acclimation regimen did not elicit significant changes in body-fluid distribution, urine production, or the concentrations of plasma protein, electrolytes or the fluid-regulatory hormones. While acclimation trends were not evident, we have confirmed that fluid from extravascular cells is displaced into the interstitium during acute cold-water immersion, both before and after cold acclimation.

  17. Determination of the rate constant for neuronal and extra-neuronal monoamine oxidase

    International Nuclear Information System (INIS)

    Cassis, L.; Ludwig, J.; Trendelenburg, U.

    1986-01-01

    In the rat vas deferens, neuronal deamination of 3 H-(-) noradrenaline ( 3 H-NA) to 3 H-dihydroxyphenethylglycol ( 3 HDOPEG) cannot be inhibited by pretreatment with a monoamine oxidase (MAO) inhibitor. However, in the extraneuronal compartment of the rat heart, inhibition of MAO abolishes the formation of 3 HDOPEG. To clarify this discrepancy, the authors determined the rate constant for MAO (/sup k/mao/) neuronally (rat vas deferens) and extraneuronally (rat heart). For neuronal /sup k/mao, vasa deferentia were incubated with 3 HNA for 300 minutes, and the cumulative formation of 3 HDOPEG measured. The delay in time before 3 HDOPEG achieves steady state (/sup tau/system), is inversely proportional to /sup k/mao. Because /sup tau/system is very short for neuronal MAO, an appreciable delay was only achieved after partial inhibition of MAO with various parglyline concentrations. To relate to the uninhibited enzyme, the percentage inhibition by pargyline was then determined in homogenate preparations. For extraneuronal MAO, a similar procedure was performed in perfused rat hearts. Results show a significantly greater /sup k/mao of neuronal origin, (/sup k/mao = .57min - 1) which when related to the fractional size of the neuronal compartment suggests a very high activity of neuronal MAO

  18. The Relevance of AgRP Neuron-Derived GABA Inputs to POMC Neurons Differs for Spontaneous and Evoked Release.

    Science.gov (United States)

    Rau, Andrew R; Hentges, Shane T

    2017-08-02

    Hypothalamic agouti-related peptide (AgRP) neurons potently stimulate food intake, whereas proopiomelanocortin (POMC) neurons inhibit feeding. Whether AgRP neurons exert their orexigenic actions, at least in part, by inhibiting anorexigenic POMC neurons remains unclear. Here, the connectivity between GABA-releasing AgRP neurons and POMC neurons was examined in brain slices from male and female mice. GABA-mediated spontaneous IPSCs (sIPSCs) in POMC neurons were unaffected by disturbing GABA release from AgRP neurons either by cell type-specific deletion of the vesicular GABA transporter or by expression of botulinum toxin in AgRP neurons to prevent vesicle-associated membrane protein 2-dependent vesicle fusion. Additionally, there was no difference in the ability of μ-opioid receptor (MOR) agonists to inhibit sIPSCs in POMC neurons when MORs were deleted from AgRP neurons, and activation of the inhibitory designer receptor hM4Di on AgRP neurons did not affect sIPSCs recorded from POMC neurons. These approaches collectively indicate that AgRP neurons do not significantly contribute to the strong spontaneous GABA input to POMC neurons. Despite these observations, optogenetic stimulation of AgRP neurons reliably produced evoked IPSCs in POMC neurons, leading to the inhibition of POMC neuron firing. Thus, AgRP neurons can potently affect POMC neuron function without contributing a significant source of spontaneous GABA input to POMC neurons. Together, these results indicate that the relevance of GABAergic inputs from AgRP to POMC neurons is state dependent and highlight the need to consider different types of transmitter release in circuit mapping and physiologic regulation. SIGNIFICANCE STATEMENT Agouti-related peptide (AgRP) neurons play an important role in driving food intake, while proopiomelanocortin (POMC) neurons inhibit feeding. Despite the importance of these two well characterized neuron types in maintaining metabolic homeostasis, communication between these

  19. Frequent extreme cold exposure and brown fat and cold-induced thermogenesis: A study in a monozygotic twin

    NARCIS (Netherlands)

    M.J. Vosselman (Maarten J.); G.H.E.J. Vijgen (Guy H. E. J.); B.R.M. Kingma (Boris R. M.); B. Brans (Boudewijn); W.D. Van Marken Lichtenbelt (Wouter D.)

    2014-01-01

    textabstractIntroduction: Mild cold acclimation is known to increase brown adipose tissue (BAT) activity and cold-induced thermogenesis (CIT) in humans. We here tested the effect of a lifestyle with frequent exposure to extreme cold on BAT and CIT in a Dutch man known as 'the Iceman', who has

  20. Finger cold-induced vasodilation of older Korean female divers, haenyeo: effects of chronic cold exposure and aging

    Science.gov (United States)

    Lee, Joo-Young; Park, Joonhee; Koh, Eunsook; Cha, Seongwon

    2017-07-01

    The aim of the present study was to evaluate the local cold tolerance of older Korean female divers, haenyeo ( N = 22) in terms of cold acclimatization and ageing. As control groups, older non-diving females ( N = 25) and young females from a rural area ( N = 15) and an urban area ( N = 51) participated in this study. To evaluate local cold tolerance, finger cold-induced vasodilation (CIVD) during finger immersion of 4 °C water was examined. As a result, older haenyeos showed greater minimum finger temperature and recovery finger temperature than older non-diving females ( P < 0.05), but similar responses in onset time, peak time, maximum finger temperature, frequency of CIVD, heart rate, blood pressure, and thermal and pain sensations as those of older non-diving females. Another novel finding was that young urban females showed more vulnerable responses to local cold in CIVD variables and subjective sensations when compared to older females, whereas young rural females had the most excellent cold tolerance in terms of maximum temperature and frequency of CIVD among the four groups ( P < 0.05). The present results imply that older haenyeos still retain cold acclimatized features on the periphery even though they changed their cotton diving suits to wet suits in the early 1980s. However, cardiovascular responses and subjective sensations to cold reflect aging effects. In addition, we suggest that young people who have been adapted to highly insulated clothing and indoor heating systems in winter should be distinguished from young people who were exposed to less modern conveniences when compared to the aged in terms of cold tolerance.

  1. Co-micellized Pluronic mixture with thermo-sensitivity and residence stability as an injectable tissue adhesion barrier hydrogel.

    Science.gov (United States)

    Oh, Se Heang; Kang, Jun Goo; Lee, Jin Ho

    2018-01-01

    Although the tissue adhesion which leads to various complications frequently occurs after surgery, the development of an ideal tissue adhesion barrier is still a challenge. In this study, a thermo-sensitive hydrogel, which can fulfill the essential requirements of tissue adhesion barrier (that is, ease of handling for surgeon, flowing down prevention after application, stable residence on the injury during wound healing, and no use of toxic additives), was developed using biocompatible polyethylene glycol-polypropylene glycol copolymers (Pluronic F127/F68/P123 mixture). From the in vitro cell culture and in vivo animal study, it was observed that the Pluronic mixtures showed sol-gel transition at approximately body temperature (for easy injection or coating on the injury site and flowing down prevention after application) and prolonged residence stability in aqueous environment (> ∼7 days for stable protection of injury tissues/organs during wound healing), and thus was highly effective for the prevention of tissue adhesion without adverse tissue responses. Based on these results, the Pluronic F127/F68/P123 mixture itself (without any additives) can be a good candidate as an injectable or coatable tissue adhesion barrier hydrogel applicable to various injury tissues in terms of ease of use, effectiveness, and safety. © 2016 Wiley Periodicals, Inc. J Biomed Mater Res Part B: Appl Biomater, 106B: 172-182, 2018. © 2016 Wiley Periodicals, Inc.

  2. The straintronic spin-neuron

    International Nuclear Information System (INIS)

    Biswas, Ayan K; Bandyopadhyay, Supriyo; Atulasimha, Jayasimha

    2015-01-01

    In artificial neural networks, neurons are usually implemented with highly dissipative CMOS-based operational amplifiers. A more energy-efficient implementation is a ‘spin-neuron’ realized with a magneto-tunneling junction (MTJ) that is switched with a spin-polarized current (representing weighted sum of input currents) that either delivers a spin transfer torque or induces domain wall motion in the soft layer of the MTJ to mimic neuron firing. Here, we propose and analyze a different type of spin-neuron in which the soft layer of the MTJ is switched with mechanical strain generated by a voltage (representing weighted sum of input voltages) and term it straintronic spin-neuron. It dissipates orders of magnitude less energy in threshold operations than the traditional current-driven spin neuron at 0 K temperature and may even be faster. We have also studied the room-temperature firing behaviors of both types of spin neurons and find that thermal noise degrades the performance of both types, but the current-driven type is degraded much more than the straintronic type if both are optimized for maximum energy-efficiency. On the other hand, if both are designed to have the same level of thermal degradation, then the current-driven version will dissipate orders of magnitude more energy than the straintronic version. Thus, the straintronic spin-neuron is superior to current-driven spin neurons. (paper)

  3. Metabolic reprogramming during neuronal differentiation.

    Science.gov (United States)

    Agostini, M; Romeo, F; Inoue, S; Niklison-Chirou, M V; Elia, A J; Dinsdale, D; Morone, N; Knight, R A; Mak, T W; Melino, G

    2016-09-01

    Newly generated neurons pass through a series of well-defined developmental stages, which allow them to integrate into existing neuronal circuits. After exit from the cell cycle, postmitotic neurons undergo neuronal migration, axonal elongation, axon pruning, dendrite morphogenesis and synaptic maturation and plasticity. Lack of a global metabolic analysis during early cortical neuronal development led us to explore the role of cellular metabolism and mitochondrial biology during ex vivo differentiation of primary cortical neurons. Unexpectedly, we observed a huge increase in mitochondrial biogenesis. Changes in mitochondrial mass, morphology and function were correlated with the upregulation of the master regulators of mitochondrial biogenesis, TFAM and PGC-1α. Concomitant with mitochondrial biogenesis, we observed an increase in glucose metabolism during neuronal differentiation, which was linked to an increase in glucose uptake and enhanced GLUT3 mRNA expression and platelet isoform of phosphofructokinase 1 (PFKp) protein expression. In addition, glutamate-glutamine metabolism was also increased during the differentiation of cortical neurons. We identified PI3K-Akt-mTOR signalling as a critical regulator role of energy metabolism in neurons. Selective pharmacological inhibition of these metabolic pathways indicate existence of metabolic checkpoint that need to be satisfied in order to allow neuronal differentiation.

  4. A dual-targeting strategy for enhanced drug delivery and synergistic therapy based on thermosensitive nanoparticles.

    Science.gov (United States)

    Wang, Mingxin; You, Chaoqun; Gao, Zhiguo; Wu, Hongshuai; Sun, Baiwang; Zhu, Xiaoli; Chen, Renjie

    2018-08-01

    The functionalized nanoparticles have been widely studied and reported as carriers of drug transport recently. Furthermore, many groups have focused more on developing novel and efficient treatment methods, such as photodynamic therapy and photothermal therapy, since both therapies have shown inspiring potential in the application of antitumor. The mentioned treatments exhibited the superiority of cooperative manner and showed the ability to compensate for the adverse effects caused by conventional monotherapy in proposed strategies. In view of the above descriptions, we formulated a thermosensitive drug delivery system, which achieved the enhanced delivery of cisplatin and two photosensitizers (ICG and Ce6) by dual-targeting traction. Drawing on the thin film hydration method, cisplatin and photosensitizers were encapsulated inside nanoparticles. Meanwhile, the targeting peptide cRGD and targeting molecule folate can be modified on the surface of nanoparticles to realize the active identification of tumor cells. The measurements of dynamic light scattering showed that the prepared nanoparticles had an ideal dispersibility and uniform particle size of 102.6 nm. On the basis of the results observed from confocal laser scanning microscope, the modified nanoparticles were more efficient endocytosed by MCF-7 cells as a contrast to SGC-7901 cells. Photothermal conversion-triggered drug release and photo-therapies produced a significant apoptosis rate of 85.9% on MCF-7 cells. The distinguished results made it believed that the formulated delivery system had conducted great efforts and innovations for the realization of concise collaboration and provided a promising strategy for the treatment of breast cancer.

  5. A novel perspective on neuron study: damaging and promoting effects in different neurons induced by mechanical stress.

    Science.gov (United States)

    Wang, Yazhou; Wang, Wei; Li, Zong; Hao, Shilei; Wang, Bochu

    2016-10-01

    A growing volume of experimental evidence demonstrates that mechanical stress plays a significant role in growth, proliferation, apoptosis, gene expression, electrophysiological properties and many other aspects of neurons. In this review, first, the mechanical microenvironment and properties of neurons under in vivo conditions are introduced and analyzed. Second, research works in recent decades on the effects of different mechanical forces, especially compression and tension, on various neurons, including dorsal root ganglion neurons, retinal ganglion cells, cerebral cortex neurons, hippocampus neurons, neural stem cells, and other neurons, are summarized. Previous research results demonstrate that mechanical stress can not only injure neurons by damaging their morphology, impacting their electrophysiological characteristics and gene expression, but also promote neuron self-repair. Finally, some future perspectives in neuron research are discussed.

  6. Survival motor neuron protein in motor neurons determines synaptic integrity in spinal muscular atrophy.

    Science.gov (United States)

    Martinez, Tara L; Kong, Lingling; Wang, Xueyong; Osborne, Melissa A; Crowder, Melissa E; Van Meerbeke, James P; Xu, Xixi; Davis, Crystal; Wooley, Joe; Goldhamer, David J; Lutz, Cathleen M; Rich, Mark M; Sumner, Charlotte J

    2012-06-20

    The inherited motor neuron disease spinal muscular atrophy (SMA) is caused by deficient expression of survival motor neuron (SMN) protein and results in severe muscle weakness. In SMA mice, synaptic dysfunction of both neuromuscular junctions (NMJs) and central sensorimotor synapses precedes motor neuron cell death. To address whether this synaptic dysfunction is due to SMN deficiency in motor neurons, muscle, or both, we generated three lines of conditional SMA mice with tissue-specific increases in SMN expression. All three lines of mice showed increased survival, weights, and improved motor behavior. While increased SMN expression in motor neurons prevented synaptic dysfunction at the NMJ and restored motor neuron somal synapses, increased SMN expression in muscle did not affect synaptic function although it did improve myofiber size. Together these data indicate that both peripheral and central synaptic integrity are dependent on motor neurons in SMA, but SMN may have variable roles in the maintenance of these different synapses. At the NMJ, it functions at the presynaptic terminal in a cell-autonomous fashion, but may be necessary for retrograde trophic signaling to presynaptic inputs onto motor neurons. Importantly, SMN also appears to function in muscle growth and/or maintenance independent of motor neurons. Our data suggest that SMN plays distinct roles in muscle, NMJs, and motor neuron somal synapses and that restored function of SMN at all three sites will be necessary for full recovery of muscle power.

  7. Physical exercise prevents stress-induced activation of granule neurons and enhances local inhibitory mechanisms in the dentate gyrus.

    Science.gov (United States)

    Schoenfeld, Timothy J; Rada, Pedro; Pieruzzini, Pedro R; Hsueh, Brian; Gould, Elizabeth

    2013-05-01

    Physical exercise is known to reduce anxiety. The ventral hippocampus has been linked to anxiety regulation but the effects of running on this subregion of the hippocampus have been incompletely explored. Here, we investigated the effects of cold water stress on the hippocampus of sedentary and runner mice and found that while stress increases expression of the protein products of the immediate early genes c-fos and arc in new and mature granule neurons in sedentary mice, it has no such effect in runners. We further showed that running enhances local inhibitory mechanisms in the hippocampus, including increases in stress-induced activation of hippocampal interneurons, expression of vesicular GABA transporter (vGAT), and extracellular GABA release during cold water swim stress. Finally, blocking GABAA receptors in the ventral hippocampus, but not the dorsal hippocampus, with the antagonist bicuculline, reverses the anxiolytic effect of running. Together, these results suggest that running improves anxiety regulation by engaging local inhibitory mechanisms in the ventral hippocampus.

  8. Leptin signaling in GABA neurons, but not glutamate neurons, is required for reproductive function.

    Science.gov (United States)

    Zuure, Wieteke A; Roberts, Amy L; Quennell, Janette H; Anderson, Greg M

    2013-11-06

    The adipocyte-derived hormone leptin acts in the brain to modulate the central driver of fertility: the gonadotropin releasing hormone (GnRH) neuronal system. This effect is indirect, as GnRH neurons do not express leptin receptors (LEPRs). Here we test whether GABAergic or glutamatergic neurons provide the intermediate pathway between the site of leptin action and the GnRH neurons. Leptin receptors were deleted from GABA and glutamate neurons using Cre-Lox transgenics, and the downstream effects on puberty onset and reproduction were examined. Both mouse lines displayed the expected increase in body weight and region-specific loss of leptin signaling in the hypothalamus. The GABA neuron-specific LEPR knock-out females and males showed significantly delayed puberty onset. Adult fertility observations revealed that these knock-out animals have decreased fecundity. In contrast, glutamate neuron-specific LEPR knock-out mice displayed normal fertility. Assessment of the estrogenic hypothalamic-pituitary-gonadal axis regulation in females showed that leptin action on GABA neurons is not necessary for estradiol-mediated suppression of tonic luteinizing hormone secretion (an indirect measure of GnRH neuron activity) but is required for regulation of a full preovulatory-like luteinizing hormone surge. In conclusion, leptin signaling in GABAergic (but not glutamatergic neurons) plays a critical role in the timing of puberty onset and is involved in fertility regulation throughout adulthood in both sexes. These results form an important step in explaining the role of central leptin signaling in the reproductive system. Limiting the leptin-to-GnRH mediators to GABAergic cells will enable future research to focus on a few specific types of neurons.

  9. Progranulin is expressed within motor neurons and promotes neuronal cell survival

    Directory of Open Access Journals (Sweden)

    Kay Denis G

    2009-10-01

    Full Text Available Abstract Background Progranulin is a secreted high molecular weight growth factor bearing seven and one half copies of the cysteine-rich granulin-epithelin motif. While inappropriate over-expression of the progranulin gene has been associated with many cancers, haploinsufficiency leads to atrophy of the frontotemporal lobes and development of a form of dementia (frontotemporal lobar degeneration with ubiquitin positive inclusions, FTLD-U associated with the formation of ubiquitinated inclusions. Recent reports indicate that progranulin has neurotrophic effects, which, if confirmed would make progranulin the only neuroprotective growth factor that has been associated genetically with a neurological disease in humans. Preliminary studies indicated high progranulin gene expression in spinal cord motor neurons. However, it is uncertain what the role of Progranulin is in normal or diseased motor neuron function. We have investigated progranulin gene expression and subcellular localization in cultured mouse embryonic motor neurons and examined the effect of progranulin over-expression and knockdown in the NSC-34 immortalized motor neuron cell line upon proliferation and survival. Results In situ hybridisation and immunohistochemical techniques revealed that the progranulin gene is highly expressed by motor neurons within the mouse spinal cord and in primary cultures of dissociated mouse embryonic spinal cord-dorsal root ganglia. Confocal microscopy coupled to immunocytochemistry together with the use of a progranulin-green fluorescent protein fusion construct revealed progranulin to be located within compartments of the secretory pathway including the Golgi apparatus. Stable transfection of the human progranulin gene into the NSC-34 motor neuron cell line stimulates the appearance of dendritic structures and provides sufficient trophic stimulus to survive serum deprivation for long periods (up to two months. This is mediated at least in part through

  10. Hyperosmolar tears enhance cooling sensitivity of the corneal nerves in rats: possible neural basis for cold-induced dry eye pain.

    Science.gov (United States)

    Hirata, Harumitsu; Rosenblatt, Mark I

    2014-08-19

    Tear hyperosmolarity is a ubiquitous feature of dry-eye disease. Although dry-eye patients' sensitivity to cooling is well known, the effects of tear hyperosmolarity on a small amount of cooling in the corneal nerves have not been quantitatively examined. Recently reported corneal afferents, high-threshold cold sensitive plus dry-sensitive (HT-CS + DS) neurons, in rats is normally excited by strong (>4°C) cooling of the cornea, which, when applied to healthy humans, evokes the sensation of discomfort. However, corneal cooling measured between blinks does not exceed 2°C normally. Thus, we sought to determine if these nociceptors could be sensitized by hyperosmolar tears such that they are now activated by small cooling of the ocular surface. Trigeminal ganglion neurons innervating the cornea were extracellularly recorded in isoflurane-anesthetized rats. The responses of single corneal neurons to cooling stimuli presented in the presence of hyperosmolar (350-800 mOsm NaCl) tears were examined. The HT-CS + DS neurons with thresholds averaging 4°C cooling responded to cooling stimuli presented after 15 minutes of hyperosmolar tears with thresholds of less than 1°C. The response magnitudes also were enhanced so that the responses to small (2°C) cooling emerged, where none was observed before. These results demonstrate that after exposure to hyperosmolar tears, these nociceptive corneal neurons now begin to respond to the slight cooling normally encountered between blinks, enabling the painful information to be carried to the brain, which could explain the cooling-evoked discomfort in dry eye patients. Copyright 2014 The Association for Research in Vision and Ophthalmology, Inc.

  11. Working in the Cold

    Centers for Disease Control (CDC) Podcasts

    2016-02-08

    During the winter, many workers are outdoors, working in cold, wet, icy, or snowy conditions. Learn how to identify symptoms that tell you there may be a problem and protect yourself from cold stress.  Created: 2/8/2016 by National Institute for Occupational Safety and Health (NIOSH).   Date Released: 2/8/2016.

  12. Herpes Simplex Virus (Cold Sores)

    Science.gov (United States)

    ... Print Share Cold Sores in Children: About the Herpes Simplex Virus Page Content ​A child's toddler and ... Cold sores (also called fever blisters or oral herpes) start as small blisters that form around the ...

  13. Glass promotes the differentiation of neuronal and non-neuronal cell types in the Drosophila eye

    Science.gov (United States)

    Morrison, Carolyn A.; Chen, Hao; Cook, Tiffany; Brown, Stuart

    2018-01-01

    Transcriptional regulators can specify different cell types from a pool of equivalent progenitors by activating distinct developmental programs. The Glass transcription factor is expressed in all progenitors in the developing Drosophila eye, and is maintained in both neuronal and non-neuronal cell types. Glass is required for neuronal progenitors to differentiate as photoreceptors, but its role in non-neuronal cone and pigment cells is unknown. To determine whether Glass activity is limited to neuronal lineages, we compared the effects of misexpressing it in neuroblasts of the larval brain and in epithelial cells of the wing disc. Glass activated overlapping but distinct sets of genes in these neuronal and non-neuronal contexts, including markers of photoreceptors, cone cells and pigment cells. Coexpression of other transcription factors such as Pax2, Eyes absent, Lozenge and Escargot enabled Glass to induce additional genes characteristic of the non-neuronal cell types. Cell type-specific glass mutations generated in cone or pigment cells using somatic CRISPR revealed autonomous developmental defects, and expressing Glass specifically in these cells partially rescued glass mutant phenotypes. These results indicate that Glass is a determinant of organ identity that acts in both neuronal and non-neuronal cells to promote their differentiation into functional components of the eye. PMID:29324767

  14. Flu and Colds: In Depth

    Science.gov (United States)

    ... to prevent colds or relieve cold symptoms. Andrographis (Andrographis paniculata) Chinese herbal medicines Green tea Guided imagery Hydrotherapy ... measurements (VAS) to assess the effectiveness of standardized Andrographis paniculata extract SHA-10 in reducing the symptoms of ...

  15. HCS-Neurons: identifying phenotypic changes in multi-neuron images upon drug treatments of high-content screening.

    Science.gov (United States)

    Charoenkwan, Phasit; Hwang, Eric; Cutler, Robert W; Lee, Hua-Chin; Ko, Li-Wei; Huang, Hui-Ling; Ho, Shinn-Ying

    2013-01-01

    High-content screening (HCS) has become a powerful tool for drug discovery. However, the discovery of drugs targeting neurons is still hampered by the inability to accurately identify and quantify the phenotypic changes of multiple neurons in a single image (named multi-neuron image) of a high-content screen. Therefore, it is desirable to develop an automated image analysis method for analyzing multi-neuron images. We propose an automated analysis method with novel descriptors of neuromorphology features for analyzing HCS-based multi-neuron images, called HCS-neurons. To observe multiple phenotypic changes of neurons, we propose two kinds of descriptors which are neuron feature descriptor (NFD) of 13 neuromorphology features, e.g., neurite length, and generic feature descriptors (GFDs), e.g., Haralick texture. HCS-neurons can 1) automatically extract all quantitative phenotype features in both NFD and GFDs, 2) identify statistically significant phenotypic changes upon drug treatments using ANOVA and regression analysis, and 3) generate an accurate classifier to group neurons treated by different drug concentrations using support vector machine and an intelligent feature selection method. To evaluate HCS-neurons, we treated P19 neurons with nocodazole (a microtubule depolymerizing drug which has been shown to impair neurite development) at six concentrations ranging from 0 to 1000 ng/mL. The experimental results show that all the 13 features of NFD have statistically significant difference with respect to changes in various levels of nocodazole drug concentrations (NDC) and the phenotypic changes of neurites were consistent to the known effect of nocodazole in promoting neurite retraction. Three identified features, total neurite length, average neurite length, and average neurite area were able to achieve an independent test accuracy of 90.28% for the six-dosage classification problem. This NFD module and neuron image datasets are provided as a freely downloadable

  16. Evaporative cooling enhanced cold storage system

    Science.gov (United States)

    Carr, P.

    1991-10-15

    The invention provides an evaporatively enhanced cold storage system wherein a warm air stream is cooled and the cooled air stream is thereafter passed into contact with a cold storage unit. Moisture is added to the cooled air stream prior to or during contact of the cooled air stream with the cold storage unit to effect enhanced cooling of the cold storage unit due to evaporation of all or a portion of the added moisture. Preferably at least a portion of the added moisture comprises water condensed during the cooling of the warm air stream. 3 figures.

  17. Review on Cold-Formed Steel Connections

    Science.gov (United States)

    Tan, Cher Siang; Mohammad, Shahrin; Md Tahir, Mahmood; Shek, Poi Ngian

    2014-01-01

    The concept of cold-formed light steel framing construction has been widespread after understanding its structural characteristics with massive research works over the years. Connection serves as one of the important elements for light steel framing in order to achieve its structural stability. Compared to hot-rolled steel sections, cold-formed steel connections perform dissimilarity due to the thin-walled behaviour. This paper aims to review current researches on cold-formed steel connections, particularly for screw connections, storage rack connections, welded connections, and bolted connections. The performance of these connections in the design of cold-formed steel structures is discussed. PMID:24688448

  18. Results on a Binding Neuron Model and Their Implications for Modified Hourglass Model for Neuronal Network

    Directory of Open Access Journals (Sweden)

    Viswanathan Arunachalam

    2013-01-01

    Full Text Available The classical models of single neuron like Hodgkin-Huxley point neuron or leaky integrate and fire neuron assume the influence of postsynaptic potentials to last till the neuron fires. Vidybida (2008 in a refreshing departure has proposed models for binding neurons in which the trace of an input is remembered only for a finite fixed period of time after which it is forgotten. The binding neurons conform to the behaviour of real neurons and are applicable in constructing fast recurrent networks for computer modeling. This paper develops explicitly several useful results for a binding neuron like the firing time distribution and other statistical characteristics. We also discuss the applicability of the developed results in constructing a modified hourglass network model in which there are interconnected neurons with excitatory as well as inhibitory inputs. Limited simulation results of the hourglass network are presented.

  19. A New Population of Parvocellular Oxytocin Neurons Controlling Magnocellular Neuron Activity and Inflammatory Pain Processing.

    Science.gov (United States)

    Eliava, Marina; Melchior, Meggane; Knobloch-Bollmann, H Sophie; Wahis, Jérôme; da Silva Gouveia, Miriam; Tang, Yan; Ciobanu, Alexandru Cristian; Triana Del Rio, Rodrigo; Roth, Lena C; Althammer, Ferdinand; Chavant, Virginie; Goumon, Yannick; Gruber, Tim; Petit-Demoulière, Nathalie; Busnelli, Marta; Chini, Bice; Tan, Linette L; Mitre, Mariela; Froemke, Robert C; Chao, Moses V; Giese, Günter; Sprengel, Rolf; Kuner, Rohini; Poisbeau, Pierrick; Seeburg, Peter H; Stoop, Ron; Charlet, Alexandre; Grinevich, Valery

    2016-03-16

    Oxytocin (OT) is a neuropeptide elaborated by the hypothalamic paraventricular (PVN) and supraoptic (SON) nuclei. Magnocellular OT neurons of these nuclei innervate numerous forebrain regions and release OT into the blood from the posterior pituitary. The PVN also harbors parvocellular OT cells that project to the brainstem and spinal cord, but their function has not been directly assessed. Here, we identified a subset of approximately 30 parvocellular OT neurons, with collateral projections onto magnocellular OT neurons and neurons of deep layers of the spinal cord. Evoked OT release from these OT neurons suppresses nociception and promotes analgesia in an animal model of inflammatory pain. Our findings identify a new population of OT neurons that modulates nociception in a two tier process: (1) directly by release of OT from axons onto sensory spinal cord neurons and inhibiting their activity and (2) indirectly by stimulating OT release from SON neurons into the periphery. Copyright © 2016 Elsevier Inc. All rights reserved.

  20. Neurochemistry of neurons in the ventrolateral medulla activated by hypotension: Are the same neurons activated by glucoprivation?

    Science.gov (United States)

    Parker, Lindsay M; Le, Sheng; Wearne, Travis A; Hardwick, Kate; Kumar, Natasha N; Robinson, Katherine J; McMullan, Simon; Goodchild, Ann K

    2017-06-15

    Previous studies have demonstrated that a range of stimuli activate neurons, including catecholaminergic neurons, in the ventrolateral medulla. Not all catecholaminergic neurons are activated and other neurochemical content is largely unknown hence whether stimulus specific populations exist is unclear. Here we determine the neurochemistry (using in situ hybridization) of catecholaminergic and noncatecholaminergic neurons which express c-Fos immunoreactivity throughout the rostrocaudal extent of the ventrolateral medulla, in Sprague Dawley rats treated with hydralazine or saline. Distinct neuronal populations containing PPCART, PPPACAP, and PPNPY mRNAs, which were largely catecholaminergic, were activated by hydralazine but not saline. Both catecholaminergic and noncatecholaminergic neurons containing preprotachykinin and prepro-enkephalin (PPE) mRNAs were also activated, with the noncatecholaminergic population located in the rostral C1 region. Few GlyT2 neurons were activated. A subset of these data was then used to compare the neuronal populations activated by 2-deoxyglucose evoked glucoprivation (Brain Structure and Function (2015) 220:117). Hydralazine activated more neurons than 2-deoxyglucose but similar numbers of catecholaminergic neurons. Commonly activated populations expressing PPNPY and PPE mRNAs were defined. These likely include PPNPY expressing catecholaminergic neurons projecting to vasopressinergic and corticotrophin releasing factor neurons in the paraventricular nucleus, which when activated result in elevated plasma vasopressin and corticosterone. Stimulus specific neurons included noncatecholaminergic neurons and a few PPE positive catecholaminergic neuron but neurochemical codes were largely unidentified. Reasons for the lack of identification of stimulus specific neurons, readily detectable using electrophysiology in anaesthetized preparations and for which neural circuits can be defined, are discussed. © 2017 Wiley Periodicals, Inc.

  1. Improving Blast Resistance of a Thermo-Sensitive Genic Male Sterile Rice Line GD-8S by Molecular Marker-Assisted Selection

    Directory of Open Access Journals (Sweden)

    Wu-ge LIU

    2008-09-01

    Full Text Available The broad-spectrum blast resistance gene Pi-1, from donor line BL122, was introduced into a thermo-sensitive genic male sterile rice line GD-8S, which possessed good grain quality but high susceptibility to rice blast, by using backcross breeding and molecular marker-assisted selection. Five elite improved male sterile lines, RGD8S-1, RGD8S-2, RGD8S-3, RGD8S-4 and RGD8S-5, were selected based on the results of molecular marker analysis, spikelet sterility, recovery rate of genetic background and agronomic traits. Thirty-three representative blast isolates collected from Guangdong Province, China were used to inoculate the improved lines and the original line GD-8S artificially. The resistance frequencies of the improved lines ranged from 76.47% to 100%, much higher than that of the original line GD-8S (9.09%. On the agronomic characters, there were no significant differences between the improved lines and GD-8S except for flag leaf length and panicle number per plant. The improved lines could be used for breeding hybrid rice with high blast resistance.

  2. Neuronal growth on L- and D-cysteine self-assembled monolayers reveals neuronal chiral sensitivity.

    Science.gov (United States)

    Baranes, Koby; Moshe, Hagay; Alon, Noa; Schwartz, Shmulik; Shefi, Orit

    2014-05-21

    Studying the interaction between neuronal cells and chiral molecules is fundamental for the design of novel biomaterials and drugs. Chirality influences all biological processes that involve intermolecular interaction. One common method used to study cellular interactions with different enantiomeric targets is the use of chiral surfaces. Based on previous studies that demonstrated the importance of cysteine in the nervous system, we studied the effect of L- and D-cysteine on single neuronal growth. L-Cysteine, which normally functions as a neuromodulator or a neuroprotective antioxidant, causes damage at elevated levels, which may occur post trauma. In this study, we grew adult neurons in culture enriched with L- and D-cysteine as free compounds or as self-assembled monolayers of chiral surfaces and examined the effect on the neuronal morphology and adhesion. Notably, we have found that exposure to the L-cysteine enantiomer inhibited, and even prevented, neuronal attachment more severely than exposure to the D-cysteine enantiomer. Atop the L-cysteine surfaces, neuronal growth was reduced and degenerated. Since the cysteine molecules were attached to the surface via the thiol groups, the neuronal membrane was exposed to the molecular chiral site. Thus, our results have demonstrated high neuronal chiral sensitivity, revealing chiral surfaces as indirect regulators of neuronal cells and providing a reference for studying chiral drugs.

  3. Chlorophyll fluorescence emission can screen cold tolerance of cold acclimated Arabidopsis thaliana accessions

    Czech Academy of Sciences Publication Activity Database

    Mishra, Anamika; Heyer, A. G.; Mishra, Kumud

    2014-01-01

    Roč. 10, č. 38 (2014) ISSN 1746-4811 R&D Projects: GA MŠk EE2.3.20.0246; GA MŠk 7E12047 Institutional support: RVO:67179843 Keywords : high-throughput screening * chlorophyll a fluorescence transients * cold tolerance * cold acclimation * whole plant * Arabidopsis thaliana Subject RIV: EH - Ecology, Behaviour Impact factor: 3.102, year: 2014

  4. Disruption of astrocyte-neuron cholesterol cross talk affects neuronal function in Huntington's disease.

    Science.gov (United States)

    Valenza, M; Marullo, M; Di Paolo, E; Cesana, E; Zuccato, C; Biella, G; Cattaneo, E

    2015-04-01

    In the adult brain, neurons require local cholesterol production, which is supplied by astrocytes through apoE-containing lipoproteins. In Huntington's disease (HD), such cholesterol biosynthesis in the brain is severely reduced. Here we show that this defect, occurring in astrocytes, is detrimental for HD neurons. Astrocytes bearing the huntingtin protein containing increasing CAG repeats secreted less apoE-lipoprotein-bound cholesterol in the medium. Conditioned media from HD astrocytes and lipoprotein-depleted conditioned media from wild-type (wt) astrocytes were equally detrimental in a neurite outgrowth assay and did not support synaptic activity in HD neurons, compared with conditions of cholesterol supplementation or conditioned media from wt astrocytes. Molecular perturbation of cholesterol biosynthesis and efflux in astrocytes caused similarly altered astrocyte-neuron cross talk, whereas enhancement of glial SREBP2 and ABCA1 function reversed the aspects of neuronal dysfunction in HD. These findings indicate that astrocyte-mediated cholesterol homeostasis could be a potential therapeutic target to ameliorate neuronal dysfunction in HD.

  5. Neuronal Migration Disorders

    Science.gov (United States)

    ... Understanding Sleep The Life and Death of a Neuron Genes At Work In The Brain Order Publications ... birth defects caused by the abnormal migration of neurons in the developing brain and nervous system. In ...

  6. Steel weldability. Underbead cold cracking

    International Nuclear Information System (INIS)

    Marquet, F.; Defourny, J.; Bragard, A.

    1977-01-01

    The problem of underbead cold cracking has been studied by the implant technique. This approach allows to take into account in a quantitative manner the different factors acting on the cold cracking phenomenon: structure under the weld bead, level of restraint, hydrogen content in the molten metal. The influence of the metallurgical factors depending from the chemical composition of the steel has been examined. It appeared that carbon equivalent is an important factor to explain cold cracking sensitivity but that it is not sufficient to characterize the steel. The results have shown that vanadium may have a deleterious effect on the resistance to cold cracking when the hydrogen content is high and that small silicon additions are beneficient. The influence of the diffusible hydrogen content has been checked and the important action of pre- and postheating has been shown. These treatments allow the hydrogen to escape from the weld before the metal has been damaged. Some inclusions (sulphides) may also decrease the influence of hydrogen. A method based on the implant tests has been proposed which allows to choose and to control safe welding conditions regarding cold cracking

  7. High-frequency stimulation-induced peptide release synchronizes arcuate kisspeptin neurons and excites GnRH neurons

    Science.gov (United States)

    Qiu, Jian; Nestor, Casey C; Zhang, Chunguang; Padilla, Stephanie L; Palmiter, Richard D

    2016-01-01

    Kisspeptin (Kiss1) and neurokinin B (NKB) neurocircuits are essential for pubertal development and fertility. Kisspeptin neurons in the hypothalamic arcuate nucleus (Kiss1ARH) co-express Kiss1, NKB, dynorphin and glutamate and are postulated to provide an episodic, excitatory drive to gonadotropin-releasing hormone 1 (GnRH) neurons, the synaptic mechanisms of which are unknown. We characterized the cellular basis for synchronized Kiss1ARH neuronal activity using optogenetics, whole-cell electrophysiology, molecular pharmacology and single cell RT-PCR in mice. High-frequency photostimulation of Kiss1ARH neurons evoked local release of excitatory (NKB) and inhibitory (dynorphin) neuropeptides, which were found to synchronize the Kiss1ARH neuronal firing. The light-evoked synchronous activity caused robust excitation of GnRH neurons by a synaptic mechanism that also involved glutamatergic input to preoptic Kiss1 neurons from Kiss1ARH neurons. We propose that Kiss1ARH neurons play a dual role of driving episodic secretion of GnRH through the differential release of peptide and amino acid neurotransmitters to coordinate reproductive function. DOI: http://dx.doi.org/10.7554/eLife.16246.001 PMID:27549338

  8. Statistics of Visual Responses to Image Object Stimuli from Primate AIT Neurons to DNN Neurons.

    Science.gov (United States)

    Dong, Qiulei; Wang, Hong; Hu, Zhanyi

    2018-02-01

    Under the goal-driven paradigm, Yamins et al. ( 2014 ; Yamins & DiCarlo, 2016 ) have shown that by optimizing only the final eight-way categorization performance of a four-layer hierarchical network, not only can its top output layer quantitatively predict IT neuron responses but its penultimate layer can also automatically predict V4 neuron responses. Currently, deep neural networks (DNNs) in the field of computer vision have reached image object categorization performance comparable to that of human beings on ImageNet, a data set that contains 1.3 million training images of 1000 categories. We explore whether the DNN neurons (units in DNNs) possess image object representational statistics similar to monkey IT neurons, particularly when the network becomes deeper and the number of image categories becomes larger, using VGG19, a typical and widely used deep network of 19 layers in the computer vision field. Following Lehky, Kiani, Esteky, and Tanaka ( 2011 , 2014 ), where the response statistics of 674 IT neurons to 806 image stimuli are analyzed using three measures (kurtosis, Pareto tail index, and intrinsic dimensionality), we investigate the three issues in this letter using the same three measures: (1) the similarities and differences of the neural response statistics between VGG19 and primate IT cortex, (2) the variation trends of the response statistics of VGG19 neurons at different layers from low to high, and (3) the variation trends of the response statistics of VGG19 neurons when the numbers of stimuli and neurons increase. We find that the response statistics on both single-neuron selectivity and population sparseness of VGG19 neurons are fundamentally different from those of IT neurons in most cases; by increasing the number of neurons in different layers and the number of stimuli, the response statistics of neurons at different layers from low to high do not substantially change; and the estimated intrinsic dimensionality values at the low

  9. The process and risk of the CPR1000 cold function test in the cold area

    International Nuclear Information System (INIS)

    Liu Tinghao; Zhang Jian; Ji Dapeng; Shi Quanjian; Tian Kuo

    2014-01-01

    Hong yanhe nuclear power station is the first CPR1000 reactor which is under construction in the cold area of north China. It is also the first time to carry out the cold functional test (CFT) in the winter of north China. The preparation and process of CFT are described in the paper. According to the experience feedback of CFT of Unit 1, the risk and solution which are significance for the CFT of the other NPS in the cold area are analysed. (authors)

  10. Recurrently connected and localized neuronal communities initiate coordinated spontaneous activity in neuronal networks

    Science.gov (United States)

    Amin, Hayder; Maccione, Alessandro; Nieus, Thierry

    2017-01-01

    Developing neuronal systems intrinsically generate coordinated spontaneous activity that propagates by involving a large number of synchronously firing neurons. In vivo, waves of spikes transiently characterize the activity of developing brain circuits and are fundamental for activity-dependent circuit formation. In vitro, coordinated spontaneous spiking activity, or network bursts (NBs), interleaved within periods of asynchronous spikes emerge during the development of 2D and 3D neuronal cultures. Several studies have investigated this type of activity and its dynamics, but how a neuronal system generates these coordinated events remains unclear. Here, we investigate at a cellular level the generation of network bursts in spontaneously active neuronal cultures by exploiting high-resolution multielectrode array recordings and computational network modelling. Our analysis reveals that NBs are generated in specialized regions of the network (functional neuronal communities) that feature neuronal links with high cross-correlation peak values, sub-millisecond lags and that share very similar structural connectivity motifs providing recurrent interactions. We show that the particular properties of these local structures enable locally amplifying spontaneous asynchronous spikes and that this mechanism can lead to the initiation of NBs. Through the analysis of simulated and experimental data, we also show that AMPA currents drive the coordinated activity, while NMDA and GABA currents are only involved in shaping the dynamics of NBs. Overall, our results suggest that the presence of functional neuronal communities with recurrent local connections allows a neuronal system to generate spontaneous coordinated spiking activity events. As suggested by the rules used for implementing our computational model, such functional communities might naturally emerge during network development by following simple constraints on distance-based connectivity. PMID:28749937

  11. Recurrently connected and localized neuronal communities initiate coordinated spontaneous activity in neuronal networks.

    Directory of Open Access Journals (Sweden)

    Davide Lonardoni

    2017-07-01

    Full Text Available Developing neuronal systems intrinsically generate coordinated spontaneous activity that propagates by involving a large number of synchronously firing neurons. In vivo, waves of spikes transiently characterize the activity of developing brain circuits and are fundamental for activity-dependent circuit formation. In vitro, coordinated spontaneous spiking activity, or network bursts (NBs, interleaved within periods of asynchronous spikes emerge during the development of 2D and 3D neuronal cultures. Several studies have investigated this type of activity and its dynamics, but how a neuronal system generates these coordinated events remains unclear. Here, we investigate at a cellular level the generation of network bursts in spontaneously active neuronal cultures by exploiting high-resolution multielectrode array recordings and computational network modelling. Our analysis reveals that NBs are generated in specialized regions of the network (functional neuronal communities that feature neuronal links with high cross-correlation peak values, sub-millisecond lags and that share very similar structural connectivity motifs providing recurrent interactions. We show that the particular properties of these local structures enable locally amplifying spontaneous asynchronous spikes and that this mechanism can lead to the initiation of NBs. Through the analysis of simulated and experimental data, we also show that AMPA currents drive the coordinated activity, while NMDA and GABA currents are only involved in shaping the dynamics of NBs. Overall, our results suggest that the presence of functional neuronal communities with recurrent local connections allows a neuronal system to generate spontaneous coordinated spiking activity events. As suggested by the rules used for implementing our computational model, such functional communities might naturally emerge during network development by following simple constraints on distance-based connectivity.

  12. Single neuron computation

    CERN Document Server

    McKenna, Thomas M; Zornetzer, Steven F

    1992-01-01

    This book contains twenty-two original contributions that provide a comprehensive overview of computational approaches to understanding a single neuron structure. The focus on cellular-level processes is twofold. From a computational neuroscience perspective, a thorough understanding of the information processing performed by single neurons leads to an understanding of circuit- and systems-level activity. From the standpoint of artificial neural networks (ANNs), a single real neuron is as complex an operational unit as an entire ANN, and formalizing the complex computations performed by real n

  13. Mesmerising mirror neurons.

    Science.gov (United States)

    Heyes, Cecilia

    2010-06-01

    Mirror neurons have been hailed as the key to understanding social cognition. I argue that three currents of thought-relating to evolution, atomism and telepathy-have magnified the perceived importance of mirror neurons. When they are understood to be a product of associative learning, rather than an adaptation for social cognition, mirror neurons are no longer mesmerising, but they continue to raise important questions about both the psychology of science and the neural bases of social cognition. Copyright 2010 Elsevier Inc. All rights reserved.

  14. Peripheral cold acclimatization in Antarctic scuba divers.

    Science.gov (United States)

    Bridgman, S A

    1991-08-01

    Peripheral acclimatization to cold in scuba divers stationed at the British Antarctic Survey's Signy Station was investigated during a year in Antarctica. Five divers and five non-diver controls underwent monthly laboratory tests of index finger immersion in cold water for 30 min. Index finger pulp temperature and time of onset of cold-induced vasodilatation (CIVD) were measured. Pain was recorded with verbal and numerical psychophysical subjective pain ratings. Average finger temperatures and median finger pain from 6-30 min of immersion, maximum finger temperatures during the first CIVD cycle, and finger temperatures at the onset of CIVD were calculated. Comparison of the variables recorded from divers and non-divers were performed with analysis of variance. No significant differences were found among the variables recorded from divers and non-divers. From a review of the literature, divers have responses typical of non-cold-adapted Caucasians. There is, therefore, no evidence that Signy divers peripherally acclimatized to cold. We suggest that these findings occur because either the whole body cooling which divers undergo inhibits peripheral acclimatization or because of insufficiently frequent or severe cold exposure while diving. Further basic studies on the duration, frequency and severity of cold exposure necessary to induce peripheral cold acclimatization are required before this question can be satisfactorily answered.

  15. Cold water recovery reduces anaerobic performance.

    Science.gov (United States)

    Crowe, M J; O'Connor, D; Rudd, D

    2007-12-01

    This study investigated the effects of cold water immersion on recovery from anaerobic cycling. Seventeen (13 male, 4 female) active subjects underwent a crossover, randomised design involving two testing sessions 2 - 6 d apart. Testing involved two 30-s maximal cycling efforts separated by a one-hour recovery period of 10-min cycling warm-down followed by either passive rest or 15-min cold water immersion (13 - 14 degrees C) with passive rest. Peak power, total work and postexercise blood lactate were significantly reduced following cold water immersion compared to the first exercise test and the control condition. These variables did not differ significantly between the control tests. Peak exercise heart rate was significantly lower after cold water immersion compared to the control. Time to peak power, rating of perceived exertion, and blood pH were not affected by cold water immersion compared to the control. Core temperature rose significantly (0.3 degrees C) during ice bath immersion but a similar increase also occurred in the control condition. Therefore, cold water immersion caused a significant decrease in sprint cycling performance with one-hour recovery between tests.

  16. Actively controlling coolant-cooled cold plate configuration

    Science.gov (United States)

    Chainer, Timothy J.; Parida, Pritish R.

    2015-07-28

    A method is provided to facilitate active control of thermal and fluid dynamic performance of a coolant-cooled cold plate. The method includes: monitoring a variable associated with at least one of the coolant-cooled cold plate or one or more electronic components being cooled by the cold plate; and dynamically varying, based on the monitored variable, a physical configuration of the cold plate. By dynamically varying the physical configuration, the thermal and fluid dynamic performance of the cold plate are adjusted to, for example, optimally cool the one or more electronic components, and at the same time, reduce cooling power consumption used in cooling the electronic component(s). The physical configuration can be adjusted by providing one or more adjustable plates within the coolant-cooled cold plate, the positioning of which may be adjusted based on the monitored variable.

  17. RNA-Seq-based analysis of cold shock response in Thermoanaerobacter tengcongensis, a bacterium harboring a single cold shock protein encoding gene.

    Directory of Open Access Journals (Sweden)

    Bo Liu

    Full Text Available BACKGROUND: Although cold shock responses and the roles of cold shock proteins in microorganisms containing multiple cold shock protein genes have been well characterized, related studies on bacteria possessing a single cold shock protein gene have not been reported. Thermoanaerobacter tengcongensis MB4, a thermophile harboring only one known cold shock protein gene (TtescpC, can survive from 50° to 80 °C, but has poor natural competence under cold shock at 50 °C. We therefore examined cold shock responses and their effect on natural competence in this bacterium. RESULTS: The transcriptomes of T. tengcongensis before and after cold shock were analyzed by RNA-seq and over 1200 differentially expressed genes were successfully identified. These genes were involved in a wide range of biological processes, including modulation of DNA replication, recombination, and repair; energy metabolism; production of cold shock protein; synthesis of branched amino acids and branched-chain fatty acids; and sporulation. RNA-seq analysis also suggested that T. tengcongensis initiates cell wall and membrane remodeling processes, flagellar assembly, and sporulation in response to low temperature. Expression profiles of TtecspC and failed attempts to produce a TtecspC knockout strain confirmed the essential role of TteCspC in the cold shock response, and also suggested a role of this protein in survival at optimum growth temperature. Repression of genes encoding ComEA and ComEC and low energy metabolism levels in cold-shocked cells are the likely basis of poor natural competence at low temperature. CONCLUSION: Our study demonstrated changes in global gene expression under cold shock and identified several candidate genes related to cold shock in T. tengcongensis. At the same time, the relationship between cold shock response and poor natural competence at low temperature was preliminarily elucidated. These findings provide a foundation for future studies on genetic

  18. Social science in the Cold War.

    Science.gov (United States)

    Engerman, David C

    2010-06-01

    This essay examines ways in which American social science in the late twentieth century was--and was not--a creature of the Cold War. It identifies important work by historians that calls into question the assumption that all social science during the Cold War amounts to "Cold War social science." These historians attribute significant agency to social scientists, showing how they were enmeshed in both long-running disciplinary discussions and new institutional environments. Key trends in this scholarship include a broadening historical perspective to see social scientists in the Cold War as responding to the ideas of their scholarly predecessors; identifying the institutional legacies of World War II; and examining in close detail the products of extramural--especially governmental--funding. The result is a view of social science in the Cold War in which national security concerns are relevant, but with varied and often unexpected impacts on intellectual life.

  19. Cold-inducible RNA-binding protein mediates cold air inducible airway mucin production through TLR4/NF-κB signaling pathway.

    Science.gov (United States)

    Chen, Lingxiu; Ran, Danhua; Xie, Wenyue; Xu, Qing; Zhou, Xiangdong

    2016-10-01

    Mucus overproduction is an important feature in patients with chronic inflammatory airway diseases and cold air stimulation has been shown to be associated with the severity of these diseases. However, the regulatory mechanisms that mediate excessive mucin production under cold stress remain elusive. Recently, the cold-inducible RNA-binding protein (CIRP) has been shown to be markedly induced after exposure to cold air. In this study, we sought to explore the expression of CIRP within bronchial biopsy specimens, the effect on mucin5AC (MUC5AC) production in chronic inflammatory airway diseases and the potential signaling pathways involved in cold air stimulation process. We found that CIRP protein expression was significantly increased in patients with COPD and in mice treated with cold air. Moreover, cold air stimulation induced MUC5AC expression in wild-type mice but not in CIRP(-/-) mice. In vitro, cold air stress significantly elevated the transcriptional and protein expression levels of MUC5AC in human bronchial epithelial cells. CIRP, toll-like receptor 4 (TLR4) and phosphorylated NF-κB p65 (p-p65) increased significantly in response to cold stress and CIRP siRNA, TLR4 - neutralizing Ab and a specific inhibitor of NF-κB could attenuated cold stress inducible MUC5AC expression. In addition, CIRP siRNA could hindered the expression levels of TLR4 and p-p65 both induced by cold stress. Taken together, these results suggest that airway epithelial cells constitutively express CIRP in vitro and in vivo. CIRP is responsible for cold-inducible MUC5AC expression by activating TLR4/NF-κB signaling pathway. Copyright © 2016 Elsevier B.V. All rights reserved.

  20. Accelerator-based pulsed cold neutron source

    International Nuclear Information System (INIS)

    Inoue, Kazuhiko; Iwasa, Hirokatsu; Kiyanagi, Yoshiaki

    1979-01-01

    An accelerator-based pulsed cold neutron source was constructed. The accelerator is a 35 MeV electron linear accelerator with 1 kW average beam power. The cold neutron beam intensity at a specimen is equivalent to that of a research reactor of 10 14 n/cm 2 .s thermal flux in the case of the quasi-elastic neutron scattering measurements. In spite of some limitations to the universal uses, it has been demonstrated by this facility that the modest capacity accelerator-based pulsed cold neutron source is a highly efficient cold neutron source with low capital investment. Design philosophy, construction details, performance and some operational experiences are described. (author)

  1. Heat and cold accumulators in vehicles

    Energy Technology Data Exchange (ETDEWEB)

    Kauranen, P.; Wikstroem, L. (VTT Technical Research Centre of Finland, Advanced Materials, Tampere (Finland)); Heikkinen, J. (VTT Technical Research Centre of Finland, Building Services and Indoor Environment, Espoo (Finland)); Laurikko, J.; Elonen, T. (VTT Technical Research Centre of Finland, Emission Control, Espoo (Finland)); Seppaelae, A. (Helsinki Univ. of Technology, Applied Thermodynamics, Espoo (Finland)). Email: ari.seppala@tkk.fi

    2009-07-01

    Phase Change Material (PCM) based heat and cold accumulators have been tailored for transport applications including a mail delivery van as well as the cold chains of foodstuff and blood products. The PCMs can store relative large amount of thermal energy in a narrow temperature interval as latent heat of fusion of their melting and crystallization processes. Compact heat and cold accumulators can be designed using PCMs. The aim of the project has been to reduce the exhaust gas and noise emissions and improve the fuel economy of the transport systems and to improve the reliability of the cold chains studied by storing thermal energy in PCM accumulators. (orig.)

  2. Motor Neuron Diseases

    Science.gov (United States)

    ... and other neurodegenerative diseases to better understand the function of neurons and other support cells and identify candidate therapeutic ... and other neurodegenerative diseases to better understand the function of neurons and other support cells and identify candidate therapeutic ...

  3. Facts about the Common Cold

    Science.gov (United States)

    ... different viruses. Rhinovirus is the most common cause, accounting for 10 to 40 percent of colds. Other common cold viruses include coronavirus and ... RSS | Terms Of Use | Privacy | Sitemap Our Family Of Sites ... Introduction Risk Factors Screening Symptoms Tumor Testing Summary '; var ...

  4. Leptin Action on GABAergic Neurons Prevents Obesity and Reduces Inhibitory Tone to POMC Neurons

    OpenAIRE

    Vong, Linh; Ye, Chianping; Yang, Zongfang; Choi, Brian; Chua, Streamson; Lowell, Bradford B.

    2011-01-01

    Leptin acts in the brain to prevent obesity. The underlying neurocircuitry responsible for this is poorly understood, in part due to incomplete knowledge regarding first order, leptin-responsive neurons. To address this, we and others have been removing leptin receptors from candidate first order neurons. While functionally relevant neurons have been identified, the observed effects have been small suggesting that most first order neurons remain unidentified. Here we take an alternative appro...

  5. Phonon forces and cold denaturatio

    DEFF Research Database (Denmark)

    Bohr, Jakob

    2003-01-01

    Protein unfolds upon temperature reduction as Well as upon In increase in temperature, These phenomena are called cold denaturation and hot denaturation, respectively. The contribution from quantum mode forces to denaturation is estimated using a simple phenomenological model describing the molec......Protein unfolds upon temperature reduction as Well as upon In increase in temperature, These phenomena are called cold denaturation and hot denaturation, respectively. The contribution from quantum mode forces to denaturation is estimated using a simple phenomenological model describing...... the molecule Is a continuum. The frequencies of the vibrational modes depend on the molecular dimensionality; hence, the zero-point energies for the folded and the denatured protein are estimated to differ by several electron volts. For a biomolecule such an energy is significant and may contribute to cold...... denaturing. This is consistent with the empirical observation that cold denaturation is exothermic anti hot denaturation endothermic....

  6. Learning of time series through neuron-to-neuron instruction

    Energy Technology Data Exchange (ETDEWEB)

    Miyazaki, Y [Department of Physics, Kyoto University, Kyoto 606-8502, (Japan); Kinzel, W [Institut fuer Theoretische Physik, Universitaet Wurzburg, 97074 Wurzburg (Germany); Shinomoto, S [Department of Physics, Kyoto University, Kyoto (Japan)

    2003-02-07

    A model neuron with delayline feedback connections can learn a time series generated by another model neuron. It has been known that some student neurons that have completed such learning under the instruction of a teacher's quasi-periodic sequence mimic the teacher's time series over a long interval, even after instruction has ceased. We found that in addition to such faithful students, there are unfaithful students whose time series eventually diverge exponentially from that of the teacher. In order to understand the circumstances that allow for such a variety of students, the orbit dimension was estimated numerically. The quasi-periodic orbits in question were found to be confined in spaces with dimensions significantly smaller than that of the full phase space.

  7. Learning of time series through neuron-to-neuron instruction

    International Nuclear Information System (INIS)

    Miyazaki, Y; Kinzel, W; Shinomoto, S

    2003-01-01

    A model neuron with delayline feedback connections can learn a time series generated by another model neuron. It has been known that some student neurons that have completed such learning under the instruction of a teacher's quasi-periodic sequence mimic the teacher's time series over a long interval, even after instruction has ceased. We found that in addition to such faithful students, there are unfaithful students whose time series eventually diverge exponentially from that of the teacher. In order to understand the circumstances that allow for such a variety of students, the orbit dimension was estimated numerically. The quasi-periodic orbits in question were found to be confined in spaces with dimensions significantly smaller than that of the full phase space

  8. Neurons of self-defence: neuronal innervation of the exocrine defence glands in stick insects.

    Science.gov (United States)

    Stolz, Konrad; von Bredow, Christoph-Rüdiger; von Bredow, Yvette M; Lakes-Harlan, Reinhard; Trenczek, Tina E; Strauß, Johannes

    2015-01-01

    Stick insects (Phasmatodea) use repellent chemical substances (allomones) for defence which are released from so-called defence glands in the prothorax. These glands differ in size between species, and are under neuronal control from the CNS. The detailed neural innervation and possible differences between species are not studied so far. Using axonal tracing, the neuronal innervation is investigated comparing four species. The aim is to document the complexity of defence gland innervation in peripheral nerves and central motoneurons in stick insects. In the species studied here, the defence gland is innervated by the intersegmental nerve complex (ISN) which is formed by three nerves from the prothoracic (T1) and suboesophageal ganglion (SOG), as well as a distinct suboesophageal nerve (Nervus anterior of the suboesophageal ganglion). In Carausius morosus and Sipyloidea sipylus, axonal tracing confirmed an innervation of the defence glands by this N. anterior SOG as well as N. anterior T1 and N. posterior SOG from the intersegmental nerve complex. In Peruphasma schultei, which has rather large defence glands, only the innervation by the N. anterior SOG was documented by axonal tracing. In the central nervous system of all species, 3-4 neuron types are identified by axonal tracing which send axons in the N. anterior SOG likely innervating the defence gland as well as adjacent muscles. These neurons are mainly suboesophageal neurons with one intersegmental neuron located in the prothoracic ganglion. The neuron types are conserved in the species studied, but the combination of neuron types is not identical. In addition, the central nervous system in S. sipylus contains one suboesophageal and one prothoracic neuron type with axons in the intersegmental nerve complex contacting the defence gland. Axonal tracing shows a very complex innervation pattern of the defence glands of Phasmatodea which contains different neurons in different nerves from two adjacent body segments

  9. Cold gelation of globular proteins

    NARCIS (Netherlands)

    Alting, A.C.

    2003-01-01

    Keywords : globular proteins, whey protein, ovalbumin, cold gelation, disulfide bonds, texture, gel hardnessProtein gelation in food products is important to obtain desirable sensory and textural properties. Cold gelation is a novel method to produce protein-based gels. It is a two step process in

  10. Monitoring the vaccine cold chain.

    OpenAIRE

    Cheriyan, E

    1993-01-01

    Maintaining the vaccine cold chain is an essential part of a successful immunisation programme. A continuous electronic temperature monitor helped to identify breaks in the cold chain in the community and the study led to the issue of proper guidelines and replacement of faulty equipment.

  11. Mapping of a rice thermosensitive genic male sterility gene from a TGMS mutant line

    Energy Technology Data Exchange (ETDEWEB)

    Vu Duc Quang; Nguyen Van Dong; Pham Ngoc Luong; Tran Duy Quy [Argicultural Genetics Institute, Hanoi (Viet Nam); Nguyen, Henry T. [Texas Tech Univ., Department of Plant and Soil Science, Lubbock TX (United States)

    2001-03-01

    At the Agricultural Genetics Institute (AGI), Hanoi, Vietnam, a number of thermo-sensitive genic male sterility (TGMS) homozygous rice lines have been developed by means of experimental mutagenesis followed by anther culture techniques. One of them (TGMS-1 indica mutant line) was used in this research. The critical temperature (at the period from pollen mother cell formation to the beginning of meiotic division) for TGMS-1 sterility was 24-25degC, below which the plants were fertile and above which the plants became sterile. Segregation analysis showed that the TGMS trait of the TGMS-1 mutant line was controlled by a single recessive gene. An F{sub 2} mapping population from a cross between TGMS-1 mutant line and CH1 (a fertile indica line) was developed for tagging and mapping the TGMS gene. From survey of 200 AFLP primer combinations in a bulked segregant analysis, 4 AFLP markers (E2/M5-200, E3/M16-400, E5/M12-600 and E5/M12-200) linked to TGMS-1 gene were identified and cloned. All except E2/M5-200 were found to be low-copy number sequences. The marker E5/M12-600 showed polymorphism in RFLP analysis and was closely linked to the TGMS gene at a distance of 3.3cM. This marker was subsequently mapped on chromosome 2 using doubled-haploid mapping populations derived from the crosses IR64xAzucena and CT9993xIR62666. Linkage of microsatellite marker RM27 with the TGMS gene further confirmed its location on chromosome 2. The closest marker, E5/M12-600, was sequenced so that a PCR marker can be developed for the use in marker-assisted breeding. The application of TGMS genes to the commercial two-line hybrid rice breeding system was discussed. (author)

  12. Injectable hydrogel as stem cell scaffolds from the thermosensitive terpolymer of NIPAAm/AAc/HEMAPCL

    Directory of Open Access Journals (Sweden)

    Lian S

    2012-09-01

    Full Text Available Sheng Lian,1Yan Xiao,1 Qingqing Bian,1Yu Xia,2 Changfa Guo,2 Shenguo Wang,2 Meidong Lang11Shanghai Key Laboratory of Advanced Polymeric Materials, Key Laboratory for Ultrafine Materials of Ministry of Education, School of Materials Science and Engineering, East China University of Science and Technology, Shanghai, People's Republic of China; 2Department of Cardiac Surgery, Zhongshan Hospital, Fudan University and Shanghai Institute of Cardiovascular Diseases, Shanghai, People's Republic of ChinaAbstract: A series of biodegradable thermosensitive copolymers was synthesized by free radical polymerization with N-isopropylacrylamide (NIPAAm, acrylic acid (AAc and macromer 2-hydroxylethyl methacrylate-poly(ε-caprolactone (HEMAPCL. The structure and composition of the obtained terpolymers were confirmed by proton nuclear magnetic resonance spectroscopy, while their molecular weight was measured using gel permeation chromatography. The copolymers were dissolved in phosphate-buffered saline (PBS solution (pH = 7.4 with different concentrations to prepare hydrogels. The lower critical solution temperature (LCST, cloud point, and rheological property of the hydrogels were determined by differential scanning calorimetry, ultraviolet-visible spectrometry, and rotational rheometry, respectively. It was found that LCST of the hydrogel increased significantly with the increasing NIPAAm content, and hydrogel with higher AAc/HEMAPCL ratio exhibited better storage modulus, water content, and injectability. The hydrogels were formed by maintaining the copolymer solution at 37°C. The degradation experiment on the formed hydrogels was conducted in PBS solution for 2 weeks and demonstrated a less than 20% weight loss. Scanning electron microscopy was also used to study the morphology of the hydrogel. The copolymer with NIPAAm/AAc/HEMAPCL ratio of 88:9.6:2.4 was bioconjugated with type I collagen for the purpose of biocompatibility enhancement. In-vitro cytotoxicity

  13. Mapping of a rice thermosensitive genic male sterility gene from a TGMS mutant line

    International Nuclear Information System (INIS)

    Vu Duc Quang; Nguyen Van Dong; Pham Ngoc Luong; Tran Duy Quy; Nguyen, Henry T.

    2001-01-01

    At the Agricultural Genetics Institute (AGI), Hanoi, Vietnam, a number of thermo-sensitive genic male sterility (TGMS) homozygous rice lines have been developed by means of experimental mutagenesis followed by anther culture techniques. One of them (TGMS-1 indica mutant line) was used in this research. The critical temperature (at the period from pollen mother cell formation to the beginning of meiotic division) for TGMS-1 sterility was 24-25degC, below which the plants were fertile and above which the plants became sterile. Segregation analysis showed that the TGMS trait of the TGMS-1 mutant line was controlled by a single recessive gene. An F 2 mapping population from a cross between TGMS-1 mutant line and CH1 (a fertile indica line) was developed for tagging and mapping the TGMS gene. From survey of 200 AFLP primer combinations in a bulked segregant analysis, 4 AFLP markers (E2/M5-200, E3/M16-400, E5/M12-600 and E5/M12-200) linked to TGMS-1 gene were identified and cloned. All except E2/M5-200 were found to be low-copy number sequences. The marker E5/M12-600 showed polymorphism in RFLP analysis and was closely linked to the TGMS gene at a distance of 3.3cM. This marker was subsequently mapped on chromosome 2 using doubled-haploid mapping populations derived from the crosses IR64xAzucena and CT9993xIR62666. Linkage of microsatellite marker RM27 with the TGMS gene further confirmed its location on chromosome 2. The closest marker, E5/M12-600, was sequenced so that a PCR marker can be developed for the use in marker-assisted breeding. The application of TGMS genes to the commercial two-line hybrid rice breeding system was discussed. (author)

  14. The Relevance of AgRP Neuron-Derived GABA Inputs to POMC Neurons Differs for Spontaneous and Evoked Release

    OpenAIRE

    Rau, Andrew R.; Hentges, Shane T.

    2017-01-01

    Hypothalamic agouti-related peptide (AgRP) neurons potently stimulate food intake, whereas proopiomelanocortin (POMC) neurons inhibit feeding. Whether AgRP neurons exert their orexigenic actions, at least in part, by inhibiting anorexigenic POMC neurons remains unclear. Here, the connectivity between GABA-releasing AgRP neurons and POMC neurons was examined in brain slices from male and female mice. GABA-mediated spontaneous IPSCs (sIPSCs) in POMC neurons were unaffected by disturbing GABA re...

  15. Frequent extreme cold exposure and brown fat and cold-induced thermogenesis: a study in a monozygotic twin.

    Directory of Open Access Journals (Sweden)

    Maarten J Vosselman

    Full Text Available INTRODUCTION: Mild cold acclimation is known to increase brown adipose tissue (BAT activity and cold-induced thermogenesis (CIT in humans. We here tested the effect of a lifestyle with frequent exposure to extreme cold on BAT and CIT in a Dutch man known as 'the Iceman', who has multiple world records in withstanding extreme cold challenges. Furthermore, his monozygotic twin brother who has a 'normal' sedentary lifestyle without extreme cold exposures was measured. METHODS: The Iceman (subject A and his brother (subject B were studied during mild cold (13°C and thermoneutral conditions (31°C. Measurements included BAT activity and respiratory muscle activity by [18F]FDG-PET/CT imaging and energy expenditure through indirect calorimetry. In addition, body temperatures, cardiovascular parameters, skin perfusion, and thermal sensation and comfort were measured. Finally, we determined polymorphisms for uncoupling protein-1 and β3-adrenergic receptor. RESULTS: Subjects had comparable BAT activity (A: 1144 SUVtotal and B: 1325 SUVtotal, within the range previously observed in young adult men. They were genotyped with the polymorphism for uncoupling protein-1 (G/G. CIT was relatively high (A: 40.1% and B: 41.9%, but unlike during our previous cold exposure tests in young adult men, here both subjects practiced a g-Tummo like breathing technique, which involves vigorous respiratory muscle activity. This was confirmed by high [18F]FDG-uptake in respiratory muscle. CONCLUSION: No significant differences were found between the two subjects, indicating that a lifestyle with frequent exposures to extreme cold does not seem to affect BAT activity and CIT. In both subjects, BAT was not higher compared to earlier observations, whereas CIT was very high, suggesting that g-Tummo like breathing during cold exposure may cause additional heat production by vigorous isometric respiratory muscle contraction. The results must be interpreted with caution given the

  16. Properties of cold components of symbiotic stars

    International Nuclear Information System (INIS)

    Luud, L.; Leehdyarv, L.

    1986-01-01

    Using the Blackwell-Shallis method the luminosities, temperatures and radii for cold components of symbiotic stars and for a sample of field red giants have been determined by means of infrared photometric observations. It turned out that the cold components of symbiotic stars do not differ from the normal red giants of the asymptotic branch. The masses of cold components of symbiotic stars have been found to be close to 3 M* (M* is the solar mass).The cold components of symbiotic stars do not fill their Roche lobes. About 10 times more carbon stars than the normal value in the vicinity of the Sun have been found among the cold components of symbiotic stars

  17. An FPGA-based silicon neuronal network with selectable excitability silicon neurons

    Directory of Open Access Journals (Sweden)

    Jing eLi

    2012-12-01

    Full Text Available This paper presents a digital silicon neuronal network which simulates the nerve system in creatures and has the ability to execute intelligent tasks, such as associative memory. Two essential elements, the mathematical-structure-based digital spiking silicon neuron (DSSN and the transmitter release based silicon synapse, allow the network to show rich dynamic behaviors and are computationally efficient for hardware implementation. We adopt mixed pipeline and parallel structure and shift operations to design a sufficient large and complex network without excessive hardware resource cost. The network with $256$ full-connected neurons is built on a Digilent Atlys board equipped with a Xilinx Spartan-6 LX45 FPGA. Besides, a memory control block and USB control block are designed to accomplish the task of data communication between the network and the host PC. This paper also describes the mechanism of associative memory performed in the silicon neuronal network. The network is capable of retrieving stored patterns if the inputs contain enough information of them. The retrieving probability increases with the similarity between the input and the stored pattern increasing. Synchronization of neurons is observed when the successful stored pattern retrieval occurs.

  18. Sensory neurons do not induce motor neuron loss in a human stem cell model of spinal muscular atrophy.

    Science.gov (United States)

    Schwab, Andrew J; Ebert, Allison D

    2014-01-01

    Spinal muscular atrophy (SMA) is an autosomal recessive disorder leading to paralysis and early death due to reduced SMN protein. It is unclear why there is such a profound motor neuron loss, but recent evidence from fly and mouse studies indicate that cells comprising the whole sensory-motor circuit may contribute to motor neuron dysfunction and loss. Here, we used induced pluripotent stem cells derived from SMA patients to test whether sensory neurons directly contribute to motor neuron loss. We generated sensory neurons from SMA induced pluripotent stem cells and found no difference in neuron generation or survival, although there was a reduced calcium response to depolarizing stimuli. Using co-culture of SMA induced pluripotent stem cell derived sensory neurons with control induced pluripotent stem cell derived motor neurons, we found no significant reduction in motor neuron number or glutamate transporter boutons on motor neuron cell bodies or neurites. We conclude that SMA sensory neurons do not overtly contribute to motor neuron loss in this human stem cell system.

  19. Neuron matters: electric activation of neuronal tissue is dependent on the interaction between the neuron and the electric field.

    Science.gov (United States)

    Ye, Hui; Steiger, Amanda

    2015-08-12

    In laboratory research and clinical practice, externally-applied electric fields have been widely used to control neuronal activity. It is generally accepted that neuronal excitability is controlled by electric current that depolarizes or hyperpolarizes the excitable cell membrane. What determines the amount of polarization? Research on the mechanisms of electric stimulation focus on the optimal control of the field properties (frequency, amplitude, and direction of the electric currents) to improve stimulation outcomes. Emerging evidence from modeling and experimental studies support the existence of interactions between the targeted neurons and the externally-applied electric fields. With cell-field interaction, we suggest a two-way process. When a neuron is positioned inside an electric field, the electric field will induce a change in the resting membrane potential by superimposing an electrically-induced transmembrane potential (ITP). At the same time, the electric field can be perturbed and re-distributed by the cell. This cell-field interaction may play a significant role in the overall effects of stimulation. The redistributed field can cause secondary effects to neighboring cells by altering their geometrical pattern and amount of membrane polarization. Neurons excited by the externally-applied electric field can also affect neighboring cells by ephaptic interaction. Both aspects of the cell-field interaction depend on the biophysical properties of the neuronal tissue, including geometric (i.e., size, shape, orientation to the field) and electric (i.e., conductivity and dielectricity) attributes of the cells. The biophysical basis of the cell-field interaction can be explained by the electromagnetism theory. Further experimental and simulation studies on electric stimulation of neuronal tissue should consider the prospect of a cell-field interaction, and a better understanding of tissue inhomogeneity and anisotropy is needed to fully appreciate the neural

  20. AgRP neurons regulate development of dopamine neuronal plasticity and nonfood-associated behaviors

    Science.gov (United States)

    Dietrich, Marcelo O; Bober, Jeremy; Ferreira, Jozélia G; Tellez, Luis A; Mineur, Yann S; Souza, Diogo O; Gao, Xiao-Bing; Picciotto, Marina R; Araújo, Ivan; Liu, Zhong-Wu; Horvath, Tamas L

    2012-01-01

    It is not known whether behaviors unrelated to feeding are affected by hypothalamic regulators of hunger. We found that impairment of Agouti-related protein (AgRP) circuitry by either Sirt1 knockdown in AgRP-expressing neurons or early postnatal ablation of these neurons increased exploratory behavior and enhanced responses to cocaine. In AgRP circuit–impaired mice, ventral tegmental dopamine neurons exhibited enhanced spike timing–dependent long-term potentiation, altered amplitude of miniature postsynaptic currents and elevated dopamine in basal forebrain. Thus, AgRP neurons determine the set point of the reward circuitry and associated behaviors. PMID:22729177

  1. Nonfreezing Cold-Induced Injuries

    Science.gov (United States)

    2012-01-01

    cold injury. ( Modi - fi ed from Jia J, Pollock M: The pathogenesis of non-freezing cold nerve injury: Observations in the rat, Brain 120:631, 1997...myelitis and sinus development ( Figures 7-17 to 7-19 ). Appearance and behavior of the neuropathic foot have many similarities to those of the diabetic ...foot. In the diabetic foot, infections tend to be polymicrobial with Staphylococcus aureus, Staphylococcus epidermidis, and Enterococcus and

  2. Arabidopsis COLD SHOCK DOMAIN PROTEIN2 is a RNA chaperone that is regulated by cold and developmental signals

    International Nuclear Information System (INIS)

    Sasaki, Kentaro; Kim, Myung-Hee; Imai, Ryozo

    2007-01-01

    Bacterial cold shock proteins (CSPs) are RNA chaperones that unwind RNA secondary structures. Arabidopsis COLD SHOCK DOMAIN PROTEIN2 (AtCSP2) contains a domain that is shared with bacterial CSPs. Here we showed that AtCSP2 binds to RNA and unwinds nucleic acid duplex. Heterologous expression of AtCSP2 complemented cold sensitivity of an Escherichia coli csp quadruple mutant, indicating that AtCSP2 function as a RNA chaperone in E. coli. AtCSP2 mRNA and protein levels increased during cold acclimation, but the protein accumulation was most prominent after 10 days of cold treatment. AtCSP2 promoter::GUS transgenic plants revealed that AtCSP2 is expressed only in root and shoot apical regions during vegetative growth but is expressed in reproductive organs such as pollens, ovules and embryos. These data indicated that AtCSP2 is involved in developmental processes as well as cold adaptation. Localization of AtCSP2::GFP in nucleolus and cytoplasm suggested different nuclear and cytosolic RNA targets

  3. Cold fusion anomalies more perplexing than ever

    International Nuclear Information System (INIS)

    Dagani, R.

    1989-01-01

    This article addresses the debate over research on cold fusion. Analysis is made of the research efforts that have taken place since cold fusion was first thought to have been discovered in Utah. Research in the Soviet Union on the cold fusion phenomenon is also discussed

  4. Cold and heat waves in the United States.

    Science.gov (United States)

    Barnett, A G; Hajat, S; Gasparrini, A; Rocklöv, J

    2012-01-01

    Extreme cold and heat waves, characterized by a number of cold or hot days in succession, place a strain on people's cardiovascular and respiratory systems. The increase in deaths due to these waves may be greater than that predicted by extreme temperatures alone. We examined cold and heat waves in 99 US cities for 14 years (1987-2000) and investigated how the risk of death depended on the temperature threshold used to define a wave, and a wave's timing, duration and intensity. We defined cold and heat waves using temperatures above and below cold and heat thresholds for two or more days. We tried five cold thresholds using the first to fifth percentiles of temperature, and five heat thresholds using the 95-99 percentiles. The extra wave effects were estimated using a two-stage model to ensure that their effects were estimated after removing the general effects of temperature. The increases in deaths associated with cold waves were generally small and not statistically significant, and there was even evidence of a decreased risk during the coldest waves. Heat waves generally increased the risk of death, particularly for the hottest heat threshold. Cold waves of a colder intensity or longer duration were not more dangerous. Cold waves earlier in the cool season were more dangerous, as were heat waves earlier in the warm season. In general there was no increased risk of death during cold waves above the known increased risk associated with cold temperatures. Cold or heat waves earlier in the cool or warm season may be more dangerous because of a build up in the susceptible pool or a lack of preparedness for extreme temperatures. Copyright © 2011 Elsevier Inc. All rights reserved.

  5. A pulse tube cryocooler with a cold reservoir

    Science.gov (United States)

    Zhang, X. B.; Zhang, K. H.; Qiu, L. M.; Gan, Z. H.; Shen, X.; Xiang, S. J.

    2013-02-01

    Phase difference between pressure wave and mass flow is decisive to the cooling capacity of regenerative cryocoolers. Unlike the direct phase shifting using a piston or displacer in conventional Stirling or GM cryocoolers, the pulse tube cyocooler (PTC) indirectly adjusts the cold phase due to the absence of moving parts at the cold end. The present paper proposed and validated theoretically and experimentally a novel configuration of PTC, termed cold reservoir PTC, in which a reservoir together with an adjustable orifice is connected to the cold end of the pulse tube. The impedance from the additional orifice to the cold end helps to increase the mass flow in phase with the pressure wave at the cold end. Theoretical analyses with the linear model for the orifice and double-inlet PTCs indicate that the cooling performance can be improved by introducing the cold reservoir. The preliminary experiments with a home-made single-stage GM PTC further validated the results on the premise of minor opening of the cold-end orifice.

  6. Cold Sore

    Science.gov (United States)

    ... may reduce how often they return. Symptoms A cold sore usually passes through several stages: Tingling and itching. Many people feel an itching, burning or tingling sensation around their lips for a day or so ...

  7. Asymptomatic myocardial ischemia following cold provocation

    International Nuclear Information System (INIS)

    Shea, M.J.; Deanfield, J.E.; deLandsheere, C.M.; Wilson, R.A.; Kensett, M.; Selwyn, A.P.

    1987-01-01

    Cold is thought to provoke angina in patients with coronary disease either by an increase in myocardial demand or an increase in coronary vascular resistance. We investigated and compared the effects of cold pressor stimulation and symptom-limited supine bicycle exercise on regional myocardial perfusion in 35 patients with stable angina and coronary disease and in 10 normal subjects. Regional myocardial perfusion was assessed with positron emission tomography and rubidium-82. Following cold pressor stimulation 24 of 35 patients demonstrated significant abnormalities of regional myocardial perfusion with reduced cation uptake in affected regions of myocardium: 52 +/- 9 to 43 +/- 9 (p less than 0.001 vs normal subjects). Among these 24 patients only nine developed ST depression and only seven had angina. In contrast, 29 of 35 patients underwent supine exercise, and abnormal regional myocardial perfusion occurred in all 29, with a reduction in cation intake from 48 +/- 10 to 43 +/- 14 (p less than 0.001 vs normal subjects). Angina was present in 27 of 29 and ST depression in 25 of 29. Although the absolute decrease in cation uptake was somewhat greater following cold as opposed to exercise, the peak heart rate after cold was significantly lower than that after exercise (82 +/- 12 vs 108 +/- 16 bpm, p less than 0.05). Peak systolic blood pressures after cold and exercise were similar (159 +/- 24 vs 158 +/- 28). Thus, cold produces much more frequent asymptomatic disturbances of regional myocardial perfusion in patients with stable angina and coronary disease than is suggested by pain or ECG changes

  8. Initial heating in cold cars

    NARCIS (Netherlands)

    Daanen, H.A.M.; Teunissen, L.P.J.; Hoogh, I.M. de

    2012-01-01

    During the initial minutes after entering a cold car, people feel uncomfortably cold. Six different warming systems were investigated in a small car in order to find out how to improve the feeling of comfort using 16 volunteers. The methods were: no additional warming next to a standard heating

  9. Cold neutron radiography using low power accelerator

    International Nuclear Information System (INIS)

    Kiyanagi, Yoshiaki; Iwasa, Hirokatu

    1993-01-01

    A cold neutron source which can be adopted at a low power accelerator was studied. Time-of-flight radiography using the cold neutron source was performed. It is suggested that time-of-flight cold neutron radiography has possibility to distinguish the materials more clearly than the traditional film method since large contrast differences can be obtained by using digital data of the neutron intensity at different energies from thermal to cold region. Material will be identified at the same time by this method. (author)

  10. Spiking Neurons for Analysis of Patterns

    Science.gov (United States)

    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

  11. Orexin neurons receive glycinergic innervations.

    Directory of Open Access Journals (Sweden)

    Mari Hondo

    Full Text Available Glycine, a nonessential amino-acid that acts as an inhibitory neurotransmitter in the central nervous system, is currently used as a dietary supplement to improve the quality of sleep, but its mechanism of action is poorly understood. We confirmed the effects of glycine on sleep/wakefulness behavior in mice when administered peripherally. Glycine administration increased non-rapid eye movement (NREM sleep time and decreased the amount and mean episode duration of wakefulness when administered in the dark period. Since peripheral administration of glycine induced fragmentation of sleep/wakefulness states, which is a characteristic of orexin deficiency, we examined the effects of glycine on orexin neurons. The number of Fos-positive orexin neurons markedly decreased after intraperitoneal administration of glycine to mice. To examine whether glycine acts directly on orexin neurons, we examined the effects of glycine on orexin neurons by patch-clamp electrophysiology. Glycine directly induced hyperpolarization and cessation of firing of orexin neurons. These responses were inhibited by a specific glycine receptor antagonist, strychnine. Triple-labeling immunofluorescent analysis showed close apposition of glycine transporter 2 (GlyT2-immunoreactive glycinergic fibers onto orexin-immunoreactive neurons. Immunoelectron microscopic analysis revealed that GlyT2-immunoreactive terminals made symmetrical synaptic contacts with somata and dendrites of orexin neurons. Double-labeling immunoelectron microscopy demonstrated that glycine receptor alpha subunits were localized in the postsynaptic membrane of symmetrical inhibitory synapses on orexin neurons. Considering the importance of glycinergic regulation during REM sleep, our observations suggest that glycine injection might affect the activity of orexin neurons, and that glycinergic inhibition of orexin neurons might play a role in physiological sleep regulation.

  12. Desensitization of menthol-activated cold receptors in lower extremities during local cooling in young women with a cold constitution.

    Science.gov (United States)

    Yamazaki, Fumio; Sone, Ryoko

    2017-03-01

    To test the hypothesis that topical menthol-induced reactivity of cold sensation and cutaneous vasoconstriction to local cooling is augmented in individuals with a cold constitution, we examined thermal sensation and cutaneous vasoconstrictor responses at menthol-treated and untreated sites in the legs during local skin cooling in young women complaining of chilliness (C group) and young women with no complaint as a normal control group (N group). During local skin cooling, the sensitivity to cold sensation was greater in the C group than in the N group. The application of menthol enhanced the cold sensation at a low temperature in the N group, but not in the C group. Cutaneous vasoconstrictor responses to local skin cooling were not altered by menthol treatment in either of the two groups. These findings suggest the desensitization of menthol-activated cold receptors in the legs of C group subjects, and a minor role of cold receptor activity in cutaneous vasoconstrictor response to local cooling.

  13. Creep properties of 20% cold-worked Hastelloy XR

    International Nuclear Information System (INIS)

    Kurata, Y.

    1996-01-01

    The creep properties of Hastelloy XR, in solution-treated and in 20% cold-worked conditions, were studied at 800, 900 and 1000 C. At 800 C, the steady-state creep rate and rupture ductility decrease, while rupture life increases after cold work to 20%. Although the steady-state creep rate and ductility also decrease at 900 C, the beneficial effect on rupture life disappears. Cold work to 20% enhan ces creep resistance of this alloy at 800 and 900 C due to a high density of dislocations introduced by the cold work. Rupture life of the 20% cold-worked alloy becomes shorter and the steady-state creep rate larger at 1000 C during creep of the 20% cold-worked alloy. It is emphasized that these cold work effects should be taken into consideration in design and operation of high-temperature structural components of high-temperature gas-cooled reactors. (orig.)

  14. AgRP Neurons Can Increase Food Intake during Conditions of Appetite Suppression and Inhibit Anorexigenic Parabrachial Neurons.

    Science.gov (United States)

    Essner, Rachel A; Smith, Alison G; Jamnik, Adam A; Ryba, Anna R; Trutner, Zoe D; Carter, Matthew E

    2017-09-06

    To maintain energy homeostasis, orexigenic (appetite-inducing) and anorexigenic (appetite suppressing) brain systems functionally interact to regulate food intake. Within the hypothalamus, neurons that express agouti-related protein (AgRP) sense orexigenic factors and orchestrate an increase in food-seeking behavior. In contrast, calcitonin gene-related peptide (CGRP)-expressing neurons in the parabrachial nucleus (PBN) suppress feeding. PBN CGRP neurons become active in response to anorexigenic hormones released following a meal, including amylin, secreted by the pancreas, and cholecystokinin (CCK), secreted by the small intestine. Additionally, exogenous compounds, such as lithium chloride (LiCl), a salt that creates gastric discomfort, and lipopolysaccharide (LPS), a bacterial cell wall component that induces inflammation, exert appetite-suppressing effects and activate PBN CGRP neurons. The effects of increasing the homeostatic drive to eat on feeding behavior during appetite suppressing conditions are unknown. Here, we show in mice that food deprivation or optogenetic activation of AgRP neurons induces feeding to overcome the appetite suppressing effects of amylin, CCK, and LiCl, but not LPS. AgRP neuron photostimulation can also increase feeding during chemogenetic-mediated stimulation of PBN CGRP neurons. AgRP neuron stimulation reduces Fos expression in PBN CGRP neurons across all conditions. Finally, stimulation of projections from AgRP neurons to the PBN increases feeding following administration of amylin, CCK, and LiCl, but not LPS. These results demonstrate that AgRP neurons are sufficient to increase feeding during noninflammatory-based appetite suppression and to decrease activity in anorexigenic PBN CGRP neurons, thereby increasing food intake during homeostatic need. SIGNIFICANCE STATEMENT The motivation to eat depends on the relative balance of activity in distinct brain regions that induce or suppress appetite. An abnormal amount of activity in

  15. Effects of weak electric fields on the activity of neurons and neuronal networks

    International Nuclear Information System (INIS)

    Jeffreys, J.G.R.; Deans, J.; Bikson, M.; Fox, J.

    2003-01-01

    Electric fields applied to brain tissue will affect cellular properties. They will hyperpolarise the ends of cells closest to the positive part of the field, and depolarise ends closest to the negative. In the case of neurons this affects excitability. How these changes in transmembrane potential are distributed depends on the length constant of the neuron, and on its geometry; if the neuron is electrically compact, the change in transmembrane potential becomes an almost linear function of distance in the direction of the field. Neurons from the mammalian hippocampus, maintained in tissue slices in vitro, are significantly affected by fields of around 1-5 Vm -1 . (author)

  16. Prevention of cold-associated acute inflammation in familial cold autoinflammatory syndrome by interleukin-1 receptor antagonist.

    Science.gov (United States)

    Hoffman, Hal M; Rosengren, Sanna; Boyle, David L; Cho, Jae Y; Nayar, Jyothi; Mueller, James L; Anderson, Justin P; Wanderer, Alan A; Firestein, Gary S

    Familial cold autoinflammatory syndrome (FCAS) is an autosomal dominant disorder characterised by recurrent episodes of rash, arthralgia, and fever after cold exposure. The genetic basis of this disease has been elucidated. Cryopyrin, the protein that is altered in FCAS, is one of the adaptor proteins that activate caspase 1, resulting in release of interleukin 1. An experimental cold challenge protocol was developed to study the acute inflammatory mechanisms occurring after a general cold exposure in FCAS patients and to investigate the effects of pretreatment with an antagonist of interleukin 1 receptor (IL-1Ra). ELISA, real-time PCR, and immunohistochemistry were used to measure cytokine responses. After cold challenge, untreated patients with FCAS developed rash, fever, and arthralgias within 1-4 h. Significant increases in serum concentrations of interleukin 6 and white-blood-cell counts were seen 4-8 h after cold challenge. Serum concentrations of interleukin 1 and cytokine mRNA in peripheral-blood leucocytes were not raised, but amounts of interleukin 1 protein and mRNA were high in affected skin. IL-1Ra administered before cold challenge blocked symptoms and increases in white-blood-cell counts and serum interleukin 6. The ability of IL-1Ra to prevent the clinical features and haematological and biochemical changes in patients with FCAS indicates a central role for interleukin 1beta in this disorder. Involvement of cryopyrin in activation of caspase 1 and NF-kappaB signalling suggests that it might have a role in many chronic inflammatory diseases. These findings support a new therapy for a disorder with no previously known acceptable treatment. They also offer insights into the role of interleukin 1beta in more common inflammatory diseases.

  17. The mirror-neuron system.

    Science.gov (United States)

    Rizzolatti, Giacomo; Craighero, Laila

    2004-01-01

    A category of stimuli of great importance for primates, humans in particular, is that formed by actions done by other individuals. If we want to survive, we must understand the actions of others. Furthermore, without action understanding, social organization is impossible. In the case of humans, there is another faculty that depends on the observation of others' actions: imitation learning. Unlike most species, we are able to learn by imitation, and this faculty is at the basis of human culture. In this review we present data on a neurophysiological mechanism--the mirror-neuron mechanism--that appears to play a fundamental role in both action understanding and imitation. We describe first the functional properties of mirror neurons in monkeys. We review next the characteristics of the mirror-neuron system in humans. We stress, in particular, those properties specific to the human mirror-neuron system that might explain the human capacity to learn by imitation. We conclude by discussing the relationship between the mirror-neuron system and language.

  18. Spike timing precision of neuronal circuits.

    Science.gov (United States)

    Kilinc, Deniz; Demir, Alper

    2018-04-17

    Spike timing is believed to be a key factor in sensory information encoding and computations performed by the neurons and neuronal circuits. However, the considerable noise and variability, arising from the inherently stochastic mechanisms that exist in the neurons and the synapses, degrade spike timing precision. Computational modeling can help decipher the mechanisms utilized by the neuronal circuits in order to regulate timing precision. In this paper, we utilize semi-analytical techniques, which were adapted from previously developed methods for electronic circuits, for the stochastic characterization of neuronal circuits. These techniques, which are orders of magnitude faster than traditional Monte Carlo type simulations, can be used to directly compute the spike timing jitter variance, power spectral densities, correlation functions, and other stochastic characterizations of neuronal circuit operation. We consider three distinct neuronal circuit motifs: Feedback inhibition, synaptic integration, and synaptic coupling. First, we show that both the spike timing precision and the energy efficiency of a spiking neuron are improved with feedback inhibition. We unveil the underlying mechanism through which this is achieved. Then, we demonstrate that a neuron can improve on the timing precision of its synaptic inputs, coming from multiple sources, via synaptic integration: The phase of the output spikes of the integrator neuron has the same variance as that of the sample average of the phases of its inputs. Finally, we reveal that weak synaptic coupling among neurons, in a fully connected network, enables them to behave like a single neuron with a larger membrane area, resulting in an improvement in the timing precision through cooperation.

  19. Neuro-Compatible Metabolic Glycan Labeling of Primary Hippocampal Neurons in Noncontact, Sandwich-Type Neuron-Astrocyte Coculture.

    Science.gov (United States)

    Choi, Ji Yu; Park, Matthew; Cho, Hyeoncheol; Kim, Mi-Hee; Kang, Kyungtae; Choi, Insung S

    2017-12-20

    Glycans are intimately involved in several facets of neuronal development and neuropathology. However, the metabolic labeling of surface glycans in primary neurons is a difficult task because of the neurotoxicity of unnatural monosaccharides that are used as a metabolic precursor, hindering the progress of metabolic engineering in neuron-related fields. Therefore, in this paper, we report a neurosupportive, neuron-astrocyte coculture system that neutralizes the neurotoxic effects of unnatural monosaccharides, allowing for the long-term observation and characterization of glycans in primary neurons in vitro. Polysialic acids in neurons are selectively imaged, via the metabolic labeling of sialoglycans with peracetylated N-azidoacetyl-d-mannosamine (Ac 4 ManNAz), for up to 21 DIV. Two-color labeling shows that neuronal activities, such as neurite outgrowth and recycling of membrane components, are highly dynamic and change over time during development. In addition, the insertion sites of membrane components are suggested to not be random, but be predominantly localized in developing neurites. This work provides a new research platform and also suggests advanced 3D systems for metabolic-labeling studies of glycans in primary neurons.

  20. 21 CFR 880.6085 - Hot/cold water bottle.

    Science.gov (United States)

    2010-04-01

    ... 21 Food and Drugs 8 2010-04-01 2010-04-01 false Hot/cold water bottle. 880.6085 Section 880.6085... Devices § 880.6085 Hot/cold water bottle. (a) Identification. A hot/cold water bottle is a device intended for medical purposes that is in the form of a container intended to be filled with hot or cold water...

  1. Release of a wound-healing agent from PLGA microspheres in a thermosensitive gel.

    Science.gov (United States)

    Machado, H A; Abercrombie, J J; You, T; Deluca, P P; Leung, K P

    2013-01-01

    The purpose of this research was to develop a topical microsphere delivery system in a thermosensitive 20% poloxamer 407 gel (Pluronic F127) to control release of KSL-W, a cationic antimicrobial decapeptide, for a period of 4-7 days for potential application in combat related injuries. KSL-W loaded microsphere formulations were prepared by a solvent extraction-evaporation method (water-oil-water), with poly (D,L-lactic-co-glycolic acid) (PLGA) (50 : 50, low-weight, and hydrophilic end) as the polymeric system. After optimization of the process, three formulations (A, B, and C) were prepared with different organic to water ratio of the primary emulsion while maintaining other components and manufacturing parameters constant. Formulations were characterized for surface morphology, porous nature, drug loading, in vitro drug release, and antimicrobial activity. Microspheres containing 20% peptide with porous surfaces and internal structure were prepared in satisfactory yields and in sizes varying from 25 to 50 μm. Gels of 20% Pluronic F127, which were liquid at or below 24.6°C and formed transparent films at body temperature, were used as carriers for the microspheres. Rheological studies showed a gelation temperature of 24.6°C for the 20% Pluronic F127 gel alone. Gelation temperature and viscosity of formulations A, B, and C as a function of temperature were very close to those of the carrier. A Franz diffusion cell system was used to study the release of peptide from the microspheres suspended in both, phosphate-buffered saline (PBS) and a 20% Pluronic F127 gel. In vitro release of greater than 50% peptide was found in all formulations in both PBS and the gel, and in one formulation there was a release of 75% in both PBS and the gel. Fractions collected from the release process were also tested for bactericidal activity against Staphylococcus epidermidis using the broth microdilution method and found to provide effective antimicrobial activity to warrant

  2. Quantification of VGF- and pro-SAAS-derived peptides in endocrine tissues and the brain, and their regulation by diet and cold stress.

    Science.gov (United States)

    Chakraborty, Tandra R; Tkalych, Oleg; Nanno, Daniela; Garcia, Angelo L; Devi, Lakshmi A; Salton, Stephen R J

    2006-05-17

    Two novel granin-like polypeptides, VGF and pro-SAAS, which are stored in and released from secretory vesicles and are expressed widely in nervous, endocrine, and neuroendocrine tissues, play roles in the regulation of body weight, feeding, and energy expenditure. Both VGF and pro-SAAS are cleaved into peptide fragments, several of which are biologically active. We utilized a highly sensitive and specific radioimmunoassay (RIA) to immunoreactive, pro-SAAS-derived PEN peptides, developed another against immunoreactive, VGF-derived AQEE30 peptides, and quantified these peptides in various mouse tissues and brain regions. Immunoreactive AQEE30 was most abundant in the pituitary, while brain levels were highest in hypothalamus, striatum, and frontal cortex. Immunoreactive PEN levels were highest in the pancreas and spinal cord, and in brain, PEN was most abundant in striatum, hippocampus, pons and medulla, and cortex. Since both peptides were expressed in hypothalamus, a region of the brain that controls feeding and energy expenditure, double label immunofluorescence studies were employed. These demonstrated that 42% of hypothalamic arcuate neurons coexpress VGF and SAAS peptides, and that the intracellular distributions of these peptides in arcuate neurons differed. By RIA, cold stress increased immunoreactive AQEE30 and PEN peptide levels in female but not male hypothalamus, while a high fat diet increased AQEE30 and PEN peptide levels in female but not male hippocampus. VGF and SAAS-derived peptides are therefore widely expressed in endocrine, neuroendocrine, and neural tissues, can be accurately quantified by RIA, and are differentially regulated in the brain by diet and cold stress.

  3. Thinking about the cold fusion fever

    International Nuclear Information System (INIS)

    Kitsunezaki, Akio

    1989-01-01

    The excitement since March 23 on cold fusion seems to be unprecedented evidence that the people of the world are waiting for fusion power with much enthusiasm. Cold fusion is really a surprise because it does not need high temperature and because it seems to be easy to enlarge the test tube into a useful power source if the claim by Professors Pons and Fleischmann at the University of Utah are true. The second announcement of cold fusion came from the Brigham Young University, also in the state of Utah, by Professor Jones, but his report was totally different from that given by Pons and Fleischmann. From the beginning of the 'fever', physicists have been very skeptical about cold fusion. Most of the critics and criticisms are targeted on Pons and Fleischmann rather than Jones, because not only was their paper poor but also their statements have not been scientific. They insisted that the heat came from fusion reaction, but without any scientific proof. They had not carried out the basic control experiment by running the same test with ordinary water instead of heavy water. A meeting on cold fusion was held at JAERI on May 15. At the end of the meeting, the some 260 attendants knew that cold fusion was not conceivable with the current scientific knowledge. (N.K.)

  4. Cold neutron source with self-regulation

    International Nuclear Information System (INIS)

    Kawai, T.

    2003-01-01

    A way to increase the cold neutron flux is to cool moderator from where cold neutrons are extracted. Although various kinds of cooling system are considered, the closed thermo-siphon cooling system is adopted in many institutes. The notable feature of this system is to be able to keep the liquid level stable in the moderator cell against thermal disturbances, by using self-regulation, which allows a stable supply of cold neutrons. The main part of the closed thermo-siphon consists of a condenser, a moderator transfer tube and moderator cell, which is called the hydrogen cold system. When an extra heat load is applied to the hydrogen cold system having no flow resistance in a moderator transfer tube, the system pressure rises by evaporation of liquid hydrogen. Then the boiling point of hydrogen rises. The liquefaction capacity of the condenser is increasing with a rise of temperature, because a refrigerating power of the helium refrigerator increases linearly with temperature rise of the system. Therefore, the effect of thermal heat load increase is compensated and cancelled out. The closed thermo-siphon has this feature generally, when the moderator transfer tube is designed to be no flow resistance. The report reviews the concept of self-regulation, and how to design and construct the cold neutron source with self-regulation. (author)

  5. Cold fusion

    International Nuclear Information System (INIS)

    Suh, Suk Yong; Sung, Ki Woong; Kang, Joo Sang; Lee, Jong Jik

    1995-02-01

    So called 'cold fusion phenomena' are not confirmed yet. Excess heat generation is very delicate one. Neutron generation is most reliable results, however, the records are erratic and the same results could not be repeated. So there is no reason to exclude the malfunction of testing instruments. The same arguments arise in recording 4 He, 3 He, 3 H, which are not rich in quantity basically. An experiment where plenty of 4 He were recorded is attached in appendix. The problem is that we are trying to search cold fusion which is permitted by nature or not. The famous tunneling effect in quantum mechanics will answer it, however, the most fusion rate is known to be negligible. The focus of this project is on the theme that how to increase that negligible fusion rate. 6 figs, 4 tabs, 1512 refs. (Author)

  6. From Neurons to Brain: Adaptive Self-Wiring of Neurons

    OpenAIRE

    Segev, Ronen; Ben-Jacob, Eshel

    1998-01-01

    During embryonic morpho-genesis, a collection of individual neurons turns into a functioning network with unique capabilities. Only recently has this most staggering example of emergent process in the natural world, began to be studied. Here we propose a navigational strategy for neurites growth cones, based on sophisticated chemical signaling. We further propose that the embryonic environment (the neurons and the glia cells) acts as an excitable media in which concentric and spiral chemical ...

  7. Understanding Colds: Anatomy of the Nose

    Science.gov (United States)

    ... Complications Special Features References Common Cold Understanding Colds Anatomy of the Nose The nose contains shelf-like ... white). Soft tissue, such as the eye, is gray. The maxillary sinus of adults has a volume ...

  8. Motor Neurons

    DEFF Research Database (Denmark)

    Hounsgaard, Jorn

    2017-01-01

    Motor neurons translate synaptic input from widely distributed premotor networks into patterns of action potentials that orchestrate motor unit force and motor behavior. Intercalated between the CNS and muscles, motor neurons add to and adjust the final motor command. The identity and functional...... in in vitro preparations is far from complete. Nevertheless, a foundation has been provided for pursuing functional significance of intrinsic response properties in motoneurons in vivo during motor behavior at levels from molecules to systems....

  9. High Time Resolution Measurements of VOCs from Vehicle Cold Starts: The Air Toxic Cold Start Pulse

    Science.gov (United States)

    Jobson, B. T.; Huangfu, Y.; Vanderschelden, G. S.

    2017-12-01

    Pollutants emitted during motor vehicle cold starts, especially in winter in some climates, is a significant source of winter time air pollution. While data exist for CO, NO, and total hydrocarbon emissions from federal testing procedures for vehicle emission certification, little is known about the emission rates of individual volatile organic compounds, in particular the air toxics benzene, formaldehyde, and acetaldehyde. Little is known about the VOC speciation and temperature dependence for cold starts. The US EPA vehicle emission model MOVES assumes that cold start emissions have the same speciation profile as running emissions. We examined this assumption by measuring cold start exhaust composition for 4 vehicles fueled with E10 gasoline over a temperature range of -4°C to 10°C in winter of 2015. The extra cold start emissions were determined by comparison with emissions during engine idling. In addition to CO and NOx measurements a proton transfer reaction mass spectrometer was used to measure formaldehyde, acetaldehyde, benzene, toluene, and C2-alkylbenzenes at high time resolution to compare with the cold start emission speciation profiles used in the EPA MOVES2014 model. The results show that after the vehicle was started, CO mixing ratios can reach a few percent of the exhaust and then drop to several ppmv within 2 minutes of idling, while NOx showed different temporal behaviors among the four vehicles. VOCs displayed elevated levels during cold start and the peak mixing ratios can be two orders higher than idling phase levels. Molar emission ratios relative to toluene were used to compare with the emission ratio used in MOVES2014 and we found the formaldehyde-to-toluene emission ratio was about 0.19, which is 5 times higher than the emission ratio used in MOVES2014 and the acetaldehyde-to-toluene emission ratios were 0.86-0.89, which is 8 times higher than the ones in MOVES2014. The C2-alkylbenzene-to-toluene ratio agreed well with moves. Our results

  10. Regulatory networks in pollen development under cold stress

    Directory of Open Access Journals (Sweden)

    Kamal Dev Sharma

    2016-03-01

    Full Text Available Cold stress modifies anthers’ metabolic pathways to induce pollen sterility. Cold-tolerant plants, unlike the susceptible ones, produce high proportion of viable pollen. Anthers in susceptible plants, when exposed to cold stress, increase abscisic acid (ABA metabolism and reduce ABA catabolism. Increased ABA negatively regulates expression of tapetum cell wall bound invertase and monosaccharide transport genes resulting in distorted carbohydrate pool in anther. Cold-stress also reduces endogenous levels of the bioactive gibberellins (GAs, GA4 and GA7, in susceptible anthers by repression of the GA biosynthesis genes. Here we discuss recent findings on mechanisms of cold susceptibility in anthers which determine pollen sterility. We also discuss differences in regulatory pathways between cold-stressed anthers of susceptible and tolerant plants that decide pollen sterility or viability.

  11. Crosstalks between kisspeptin neurons and somatostatin neurons are not photoperiod dependent in the ewe hypothalamus.

    Science.gov (United States)

    Dufourny, Laurence; Lomet, Didier

    2017-12-01

    Seasonal reproduction is under the control of gonadal steroid feedback, itself synchronized by day-length or photoperiod. As steroid action on GnRH neurons is mostly indirect and therefore exerted through interneurons, we looked for neuroanatomical interactions between kisspeptin (KP) neurons and somatostatin (SOM) neurons, two populations targeted by sex steroids, in three diencephalic areas involved in the central control of ovulation and/or sexual behavior: the arcuate nucleus (ARC), the preoptic area (POA) and the ventrolateral part of the ventromedial hypothalamus (VMHvl). KP is the most potent secretagogue of GnRH secretion while SOM has been shown to centrally inhibit LH pulsatile release. Notably, hypothalamic contents of these two neuropeptides vary with photoperiod in specific seasonal species. Our hypothesis is that SOM inhibits KP neuron activity and therefore indirectly modulate GnRH release and that this effect may be seasonally regulated. We used sections from ovariectomized estradiol-replaced ewes killed after photoperiodic treatment mimicking breeding or anestrus season. We performed triple immunofluorescent labeling to simultaneously detect KP, SOM and synapsin, a marker for synaptic vesicles. Sections from the POA and from the mediobasal hypothalamus were examined using a confocal microscope. Randomly selected KP or SOM neurons were observed in the POA and ARC. SOM neurons were also observed in the VMHvl. In both the ARC and POA, nearly all KP neurons presented numerous SOM contacts. SOM neurons presented KP terminals more frequently in the ARC than in the POA and VMHvl. Quantitative analysis failed to demonstrate major seasonal variations of KP and SOM interactions. Our data suggest a possible inhibitory action of SOM on all KP neurons in both photoperiodic statuses. On the other hand, the physiological significance of KP modulation of SOM neuron activity and vice versa remain to be determined. Copyright © 2017 Elsevier Inc. All rights reserved.

  12. Endocannabinoids mediate neuron-astrocyte communication.

    Science.gov (United States)

    Navarrete, Marta; Araque, Alfonso

    2008-03-27

    Cannabinoid receptors play key roles in brain function, and cannabinoid effects in brain physiology and drug-related behavior are thought to be mediated by receptors present in neurons. Neuron-astrocyte communication relies on the expression by astrocytes of neurotransmitter receptors. Yet, the expression of cannabinoid receptors by astrocytes in situ and their involvement in the neuron-astrocyte communication remain largely unknown. We show that hippocampal astrocytes express CB1 receptors that upon activation lead to phospholipase C-dependent Ca2+ mobilization from internal stores. These receptors are activated by endocannabinoids released by neurons, increasing astrocyte Ca2+ levels, which stimulate glutamate release that activates NMDA receptors in pyramidal neurons. These results demonstrate the existence of endocannabinoid-mediated neuron-astrocyte communication, revealing that astrocytes are targets of cannabinoids and might therefore participate in the physiology of cannabinoid-related addiction. They also reveal the existence of an endocannabinoid-glutamate signaling pathway where astrocytes serve as a bridge for nonsynaptic interneuronal communication.

  13. Kinetic and theoretical studies of novel biodegradable thermo-sensitive xerogels based on PEG/PVP/silica for sustained release of enrofloxacin

    Science.gov (United States)

    Ebadi, Azra; Rafati, Amir Abbas; Bavafa, Sadeghali; Mohammadi, Masoumah

    2017-12-01

    This study involves the synthesis of a new silica-based colloidal hybrid system. In this new hybrid system, poly (ethylene glycol) (PEG) and thermo-sensitive amphiphilic biocompatible poly (vinyl pyrrolidone) (PVP) were used to create suitable storage for hydrophobic drugs. The possibility of using variable PVP/PEG molar ratios to modulate drug release rate from silica nanoparticles was a primary goal of the current research. In addition, an investigation of the drug release kinetic was conducted. To achieve this, silica nanoparticles were synthesized in poly (ethylene glycol) (PEG) and poly (vinyl pyrrolidone) (PVP) solution incorporated with enrofloxacin (EFX) (as a model hydrophobic drug), using a simple synthetic strategy of hybrid materials which avoided waste and multi-step processes. The impacts of PVP/PEG molar ratios, temperature, and pH of the release medium on release kinetic were investigated. The physicochemical properties of the drug-loaded composites were studied by Fourier transform infrared (FT-IR) spectra, scanning electron microscopy (SEM), and thermogravimetric analysis (TGA). In vitro drug release studies demonstrated that the drug release rate, which was evaluated by analyzing the experimental data with seven kinetic models in a primarily non-Fickian diffusion-controlled process, aligned well with both Ritger-Peppas and Sahlin-Peppas equations.

  14. CRISPR Epigenome Editing of AKAP150 in DRG Neurons Abolishes Degenerative IVD-Induced Neuronal Activation.

    Science.gov (United States)

    Stover, Joshua D; Farhang, Niloofar; Berrett, Kristofer C; Gertz, Jason; Lawrence, Brandon; Bowles, Robby D

    2017-09-06

    Back pain is a major contributor to disability and has significant socioeconomic impacts worldwide. The degenerative intervertebral disc (IVD) has been hypothesized to contribute to back pain, but a better understanding of the interactions between the degenerative IVD and nociceptive neurons innervating the disc and treatment strategies that directly target these interactions is needed to improve our understanding and treatment of back pain. We investigated degenerative IVD-induced changes to dorsal root ganglion (DRG) neuron activity and utilized CRISPR epigenome editing as a neuromodulation strategy. By exposing DRG neurons to degenerative IVD-conditioned media under both normal and pathological IVD pH levels, we demonstrate that degenerative IVDs trigger interleukin (IL)-6-induced increases in neuron activity to thermal stimuli, which is directly mediated by AKAP and enhanced by acidic pH. Utilizing this novel information on AKAP-mediated increases in nociceptive neuron activity, we developed lentiviral CRISPR epigenome editing vectors that modulate endogenous expression of AKAP150 by targeted promoter histone methylation. When delivered to DRG neurons, these epigenome-modifying vectors abolished degenerative IVD-induced DRG-elevated neuron activity while preserving non-pathologic neuron activity. This work elucidates the potential for CRISPR epigenome editing as a targeted gene-based pain neuromodulation strategy. Copyright © 2017 The American Society of Gene and Cell Therapy. Published by Elsevier Inc. All rights reserved.

  15. Preparation of translationally cold neutral molecules.

    Science.gov (United States)

    Di Domenicantonio, Giulia; Bertsche, Benjamin; Osterwalder, Andreas

    2011-01-01

    Efforts at EPFL to obtain translationally cold neutral molecules are described. Active deceleration of polar molecules is performed by confining the molecules in moving three-dimensional electrostatic traps, and by appropriately choosing the velocity of those traps. Alternatively, cold molecules can be obtained by velocity filtering. Here, the velocity of the molecules is not changed, but instead the cold molecules are extracted from a thermal sample by using the competition between the electrostatic force and the centrifugal force inside a bent electrostatic guide for polar molecules.

  16. The status of cold fusion

    Science.gov (United States)

    Storms, E.

    This report attempts to update the status of the phenomenon of cold fusion. The new field is continuing to grow as a variety of nuclear reactions are discovered to occur in a variety of chemical environments at modest temperatures. However, it must be cautioned that most scientists consider cold fusion as something akin to UFO's, ESP, and numerology.

  17. Axonal regeneration and neuronal function are preserved in motor neurons lacking ß-actin in vivo.

    Directory of Open Access Journals (Sweden)

    Thomas R Cheever

    2011-03-01

    Full Text Available The proper localization of ß-actin mRNA and protein is essential for growth cone guidance and axon elongation in cultured neurons. In addition, decreased levels of ß-actin mRNA and protein have been identified in the growth cones of motor neurons cultured from a mouse model of Spinal Muscular Atrophy (SMA, suggesting that ß-actin loss-of-function at growth cones or pre-synaptic nerve terminals could contribute to the pathogenesis of this disease. However, the role of ß-actin in motor neurons in vivo and its potential relevance to disease has yet to be examined. We therefore generated motor neuron specific ß-actin knock-out mice (Actb-MNsKO to investigate the function of ß-actin in motor neurons in vivo. Surprisingly, ß-actin was not required for motor neuron viability or neuromuscular junction maintenance. Skeletal muscle from Actb-MNsKO mice showed no histological indication of denervation and did not significantly differ from controls in several measurements of physiologic function. Finally, motor axon regeneration was unimpaired in Actb-MNsKO mice, suggesting that ß-actin is not required for motor neuron function or regeneration in vivo.

  18. Acetaminophen inhibits neuronal inflammation and protects neurons from oxidative stress

    Directory of Open Access Journals (Sweden)

    Grammas Paula

    2009-03-01

    Full Text Available Abstract Background Recent studies have demonstrated a link between the inflammatory response, increased cytokine formation, and neurodegeneration in the brain. The beneficial effects of anti-inflammatory drugs in neurodegenerative diseases, such as Alzheimer's disease (AD, have been documented. Increasing evidence suggests that acetaminophen has unappreciated anti-oxidant and anti-inflammatory properties. The objectives of this study are to determine the effects of acetaminophen on cultured brain neuronal survival and inflammatory factor expression when exposed to oxidative stress. Methods Cerebral cortical cultured neurons are pretreated with acetaminophen and then exposed to the superoxide-generating compound menadione (5 μM. Cell survival is assessed by MTT assay and inflammatory protein (tumor necrosis factor alpha, interleukin-1, macrophage inflammatory protein alpha, and RANTES release quantitated by ELISA. Expression of pro- and anti-apoptotic proteins is assessed by western blots. Results Acetaminophen has pro-survival effects on neurons in culture. Menadione, a superoxide releasing oxidant stressor, causes a significant (p Conclusion These data show that acetaminophen has anti-oxidant and anti-inflammatory effects on neurons and suggest a heretofore unappreciated therapeutic potential for this drug in neurodegenerative diseases such as AD that are characterized by oxidant and inflammatory stress.

  19. Hesitant birth of cold fusion

    International Nuclear Information System (INIS)

    Bockris, J.O.

    1992-01-01

    John O'M. Bockris, a distinguished chemistry professor at Texas A ampersand M University, finds the reaction to the announcement of the discovery of cold fusion curious. Two years earlier, he notes, there had been a comparable announcement concerning the discovery of high-temperature superconductivity; it received favorable press coverage for months. The cold-fusion announcement, on the other hand, was met with dour skepticism. When other researchers failed in efforts to duplicate the findings of Martin Fleischmann and B. Stanley Pons, Bockris says, the two scientists were held up to ridicule. Bockris says he found a deep emotional opposition to cold fusion, even within his own department and university. This opposition is fueled in large part, he believes, by big science and the hot fusion lobby. A key indicator of cold fusion is the presence of tritium, Brockis claims. At Texas A ampersand M, large amounts of tritium have been found in some experiments; this also has occurred in experiments at more than 40 laboratories in nine countries, he says. Excess heat production is more difficult to attain, he acknowledges. The cold-fusion controversy has uncovered some unflattering characteristics of the scientific community, Bockris says. Among them are: scientists are no less driven by emotion that business people or politicians; research funding decisions serve to perpetuate the goals of politically powerful interest groups; and ideas have great inertia once planted in a scientist's mind

  20. Public Perception of Extreme Cold Weather-Related Health Risk in a Cold Area of Northeast China.

    Science.gov (United States)

    Ban, Jie; Lan, Li; Yang, Chao; Wang, Jian; Chen, Chen; Huang, Ganlin; Li, Tiantian

    2017-08-01

    A need exists for public health strategies regarding extreme weather disasters, which in recent years have become more frequent. This study aimed to understand the public's perception of extreme cold and its related health risks, which may provide detailed information for public health preparedness during an extreme cold weather event. To evaluate public perceptions of cold-related health risk and to identify vulnerable groups, we collected responses from 891 participants in a face-to-face survey in Harbin, China. Public perception was measured by calculating the score for each perception question. Locals perceived that extreme cold weather and related health risks were serious, but thought they could not avoid these risks. The significant difference in perceived acceptance level between age groups suggested that the elderly are a "high health risk, low risk perception" group, meaning that they are relatively more vulnerable owing to their high susceptibility and low awareness of the health risks associated with extreme cold weather. The elderly should be a priority in risk communication and health protective interventions. This study demonstrated that introducing risk perception into the public health field can identify vulnerable groups with greater needs, which may improve the decision-making of public health intervention strategies. (Disaster Med Public Health Preparedness. 2017;11:417-421).

  1. Formation of cold molecules through the photo-association of cold atoms of Cesium. Existence of long range forces between between cold excited atoms of Cesium

    International Nuclear Information System (INIS)

    Comparat, D.

    1999-09-01

    This thesis deals with the experimental study and the theoretical interpretation of the processes involved in photo-association and the formation of cold caesium molecules. It also presents a study of the dipolar forces between a pair of cold excited caesium atoms. We present here the first photo-association experiment on cold caesium atoms: two cold atoms absorb a photon to form an excited electronically excited molecules in a rotation-vibration level. The first production of cold molecules which was realised experimentally, after the spontaneous deexcitation of the photo-associated molecules, is described, stressing the role of the potential well of the molecular states O g - (6s+6p 3/2 ) or 1 u (6s+6p 3/2 ) of caesium. The detection of the formed caesium molecules is based on a two-photons resonant ionisation that creates Cs 2 + ions, afterwards selectively detected. Temperatures around 20-200 μK have been measured. The photo-associative spectroscopy is described on the theoretical point of view: a detailed theoretical study allows to calculate precisely the asymptotic parts of the potential curves. On the experimental point of view, we present the spectroscopy of the extern potential well of the caesium state O g - (6s+6p 3/2 ) and the construction of an effective potential curve of the RKR type. A unified theory of photo-association in weak field, considered as a collision assisted by laser, is developed. The cold atoms experiments allow to study and control the collision between two atoms whose mutual interaction is of the dipole-dipole type. Two different physical systems are studied: a sample of Rydberg atoms, and the photo-association process which is a laser-assisted collision. A modification of the motion of one pair of atoms makes it possible to control the bipolar forces and to choose the atoms relative speeds. (author)

  2. Two cold-season derechoes in Europe

    Science.gov (United States)

    Gatzen, Christoph; Púčik, Tomas; Ryva, David

    2011-06-01

    In this study, we apply for the first time the definition of a derecho (Johns and Hirt, 1987) to European cold-season convective storm systems. These occurred on 18 January 2007 and 1 March 2008, respectively, and they are shown to fulfill the criteria of a derecho. Damaging winds were reported over a distance of 1500 km and locally reached F3 intensity. Synoptic analysis for the events reveal strongly forced situations that have been described for cold-season derechoes in the United States. A comparison of swaths of damaging winds, radar structures, detected lightning, cold pool development, and cloud-top temperatures indicates that both derechoes formed along cold fronts that were affected by strong quasi-geostrophic forcing. It seems that the overlap of the cold front position with the strong differential cyclonic vorticity advection at the cyclonic flank of mid-level jet streaks favoured intense convection and high winds. The movement and path width of the two derechoes seemed to be related to this overlap. The wind gust intensity that was also different for both events is discussed and could be related to the component of the mid-level winds perpendicular to the gust fronts.

  3. Influence of cold deformation and annealing on hydrogen embrittlement of cold hardening bainitic steel for high strength bolts

    Energy Technology Data Exchange (ETDEWEB)

    Hui, Weijun, E-mail: wjhui@bjtu.edu.cn [School of Mechanical, Electronic and Control Engineering, Beijing Jiaotong University, Beijing 100044 (China); Zhang, Yongjian; Zhao, Xiaoli; Shao, Chengwei [School of Mechanical, Electronic and Control Engineering, Beijing Jiaotong University, Beijing 100044 (China); Wang, Kaizhong; Sun, Wei; Yu, Tongren [Technical Center, Maanshan Iron & Steel Co., Ltd., Maanshan 243002, Anhui (China)

    2016-04-26

    The influence of cold drawing and annealing on hydrogen embrittlement (HE) of newly developed cold hardening bainitic steel was investigated by using slow strain rate testing (SSRT) and thermal desorption spectrometry (TDS), for ensuring safety performance of 10.9 class high strength bolts made of this kind of steel against HE under service environments. Hydrogen was introduced into the specimen by electrochemical charging. TDS analysis shows that the hydrogen-charged cold drawn specimen exhibits an additional low-temperature hydrogen desorption peak besides the original high-temperature desorption peak of the as-rolled specimen, causing remarkable increase of absorbed hydrogen content. It is found that cold drawing significantly enhances the susceptibility to HE, which is mainly attributed to remarkable increase of diffusible hydrogen absorption, the occurrence of strain-induced martensite as well as the increase of strength level. Annealing after cold deformation is an effective way to improve HE resistance and this improvement strongly depends on annealing temperature, i.e. HE susceptibility decreases slightly with increasing annealing temperature up to 200 °C and then decreases significantly with further increasing annealing temperature. This phenomenon is explained by the release of hydrogen, the recovery of cold worked microstructure and the decrease of strength with increasing annealing temperature.

  4. International cooperation in cold forging technology

    DEFF Research Database (Denmark)

    Bay, Niels; Lange, K

    1992-01-01

    International cooperation in the field of cold forging technology started in 1961 by formation of the OECD Group of Experts on Metal Forming. In 1967 this group was transformed into the International Cold Forging Group, ICFG, an independent body which has now been operative for 25 years. Members...... of the ICFG are personally elected by the Plenary as experts within the field, often representing national groups within cold forging. The main work within the ICFG is carried out in its subgroups which are established by the Plenary to collect, compile and evaluate data and eventually also produce data...... by cooperative activities or by instigating national research. These subgroups have produced 9 data sheets and 7 guidelines on subjects such as materials, tool design and construction, calculation methods for cold forging tools, manufacture of slugs, lubrication aspects and small quantity production. Plenary...

  5. Cold fusion

    Energy Technology Data Exchange (ETDEWEB)

    Suh, Suk Yong; Sung, Ki Woong; Kang, Joo Sang; Lee, Jong Jik [Korea Atomic Energy Research Institute, Taejon (Korea, Republic of)

    1995-02-01

    So called `cold fusion phenomena` are not confirmed yet. Excess heat generation is very delicate one. Neutron generation is most reliable results, however, the records are erratic and the same results could not be repeated. So there is no reason to exclude the malfunction of testing instruments. The same arguments arise in recording {sup 4}He, {sup 3}He, {sup 3}H, which are not rich in quantity basically. An experiment where plenty of {sup 4}He were recorded is attached in appendix. The problem is that we are trying to search cold fusion which is permitted by nature or not. The famous tunneling effect in quantum mechanics will answer it, however, the most fusion rate is known to be negligible. The focus of this project is on the theme that how to increase that negligible fusion rate. 6 figs, 4 tabs, 1512 refs. (Author).

  6. Neuronal avalanches and learning

    Energy Technology Data Exchange (ETDEWEB)

    Arcangelis, Lucilla de, E-mail: dearcangelis@na.infn.it [Department of Information Engineering and CNISM, Second University of Naples, 81031 Aversa (Italy)

    2011-05-01

    Networks of living neurons represent one of the most fascinating systems of biology. If the physical and chemical mechanisms at the basis of the functioning of a single neuron are quite well understood, the collective behaviour of a system of many neurons is an extremely intriguing subject. Crucial ingredient of this complex behaviour is the plasticity property of the network, namely the capacity to adapt and evolve depending on the level of activity. This plastic ability is believed, nowadays, to be at the basis of learning and memory in real brains. Spontaneous neuronal activity has recently shown features in common to other complex systems. Experimental data have, in fact, shown that electrical information propagates in a cortex slice via an avalanche mode. These avalanches are characterized by a power law distribution for the size and duration, features found in other problems in the context of the physics of complex systems and successful models have been developed to describe their behaviour. In this contribution we discuss a statistical mechanical model for the complex activity in a neuronal network. The model implements the main physiological properties of living neurons and is able to reproduce recent experimental results. Then, we discuss the learning abilities of this neuronal network. Learning occurs via plastic adaptation of synaptic strengths by a non-uniform negative feedback mechanism. The system is able to learn all the tested rules, in particular the exclusive OR (XOR) and a random rule with three inputs. The learning dynamics exhibits universal features as function of the strength of plastic adaptation. Any rule could be learned provided that the plastic adaptation is sufficiently slow.

  7. Neuronal avalanches and learning

    International Nuclear Information System (INIS)

    Arcangelis, Lucilla de

    2011-01-01

    Networks of living neurons represent one of the most fascinating systems of biology. If the physical and chemical mechanisms at the basis of the functioning of a single neuron are quite well understood, the collective behaviour of a system of many neurons is an extremely intriguing subject. Crucial ingredient of this complex behaviour is the plasticity property of the network, namely the capacity to adapt and evolve depending on the level of activity. This plastic ability is believed, nowadays, to be at the basis of learning and memory in real brains. Spontaneous neuronal activity has recently shown features in common to other complex systems. Experimental data have, in fact, shown that electrical information propagates in a cortex slice via an avalanche mode. These avalanches are characterized by a power law distribution for the size and duration, features found in other problems in the context of the physics of complex systems and successful models have been developed to describe their behaviour. In this contribution we discuss a statistical mechanical model for the complex activity in a neuronal network. The model implements the main physiological properties of living neurons and is able to reproduce recent experimental results. Then, we discuss the learning abilities of this neuronal network. Learning occurs via plastic adaptation of synaptic strengths by a non-uniform negative feedback mechanism. The system is able to learn all the tested rules, in particular the exclusive OR (XOR) and a random rule with three inputs. The learning dynamics exhibits universal features as function of the strength of plastic adaptation. Any rule could be learned provided that the plastic adaptation is sufficiently slow.

  8. Cold chain management: Knowledge and practices in primary ...

    African Journals Online (AJOL)

    Administrator

    experience and their knowledge of cold chain was not as per required levels to support effective cold chain management. ... district directorates who then supply them to the various ..... Finn L, Crook S. A district survey of vaccine cold chain ...

  9. Pathogenesis of motor neuron disease

    Institute of Scientific and Technical Information of China (English)

    Xuefei Wang

    2006-01-01

    OBJECTIVE: To summarize and analyze the factors and theories related to the attack of motor neuron disease, and comprehensively investigate the pathogenesis of motor neuron disease.DATA SOURCES: A search of Pubmed database was undertaken to identify articles about motor neuron disease published in English from January 1994 to June 2006 by using the keywords of "neurodegenerative diseases". Other literatures were collected by retrieving specific journals and articles.STUDY SELECTION: The data were checked primarily, articles related to the pathogenesis of motor neuron disease were involved, and those obviously irrelated to the articles were excluded.DATA EXTRACTION: Totally 54 articles were collected, 30 of them were involved, and the other 24 were excluded.DATA SYNTHESIS: The pathogenesis of motor neuron disease has multiple factors, and the present related theories included free radical oxidation, excitotoxicity, genetic and immune factors, lack of neurotrophic factor,injury of neurofilament, etc. The studies mainly come from transgenic animal models, cell culture in vitro and patients with familial motor neuron disease, but there are still many restrictions and disadvantages.CONCLUSION: It is necessary to try to find whether there is internal association among different mechanisms,comprehensively investigate the pathogenesis of motor neuron diseases, in order to provide reliable evidence for the clinical treatment.

  10. Prediction of cold flow properties of Biodiesel

    Directory of Open Access Journals (Sweden)

    Parag Saxena

    2016-08-01

    Full Text Available Biodiesel being environmentally friendly is fast gaining acceptance in the market as an alternate diesel fuel. But compared to petroleum diesel it has certain limitations and thus it requires further development on economic viability and improvement in its properties to use it as a commercial fuel. The cold flow properties play a major role in the usage of biodiesel commercially as it freezes at cold climatic conditions. In the present study, cold flow properties of various types of biodiesel were estimated by using correlations available in literature. The correlations were evaluated based on the deviation between the predicted value and experimental values of cold flow properties.

  11. BigNeuron: Large-Scale 3D Neuron Reconstruction from Optical Microscopy Images

    NARCIS (Netherlands)

    H. Peng (Hanchuan); M. Hawrylycz (Michael); J. Roskams (Jane); S. Hill (Sean); N. Spruston (Nelson); E. Meijering (Erik); G.A. Ascoli (Giorgio A.)

    2015-01-01

    textabstractUnderstanding the structure of single neurons is critical for understanding how they function within neural circuits. BigNeuron is a new community effort that combines modern bioimaging informatics, recent leaps in labeling and microscopy, and the widely recognized need for openness and

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

    Science.gov (United States)

    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

  13. Neuromorphic Silicon Neuron Circuits

    Science.gov (United States)

    Indiveri, Giacomo; Linares-Barranco, Bernabé; Hamilton, Tara Julia; van Schaik, André; Etienne-Cummings, Ralph; Delbruck, Tobi; Liu, Shih-Chii; Dudek, Piotr; Häfliger, Philipp; Renaud, Sylvie; Schemmel, Johannes; Cauwenberghs, Gert; Arthur, John; Hynna, Kai; Folowosele, Fopefolu; Saighi, Sylvain; Serrano-Gotarredona, Teresa; Wijekoon, Jayawan; Wang, Yingxue; Boahen, Kwabena

    2011-01-01

    Hardware implementations of spiking neurons can be extremely useful for a large variety of applications, ranging from high-speed modeling of large-scale neural systems to real-time behaving systems, to bidirectional brain–machine interfaces. The specific circuit solutions used to implement silicon neurons depend on the application requirements. In this paper we describe the most common building blocks and techniques used to implement these circuits, and present an overview of a wide range of neuromorphic silicon neurons, which implement different computational models, ranging from biophysically realistic and conductance-based Hodgkin–Huxley models to bi-dimensional generalized adaptive integrate and fire models. We compare the different design methodologies used for each silicon neuron design described, and demonstrate their features with experimental results, measured from a wide range of fabricated VLSI chips. PMID:21747754

  14. Neuromorphic silicon neuron circuits

    Directory of Open Access Journals (Sweden)

    Giacomo eIndiveri

    2011-05-01

    Full Text Available Hardware implementations of spiking neurons can be extremely useful for a large variety of applications, ranging from high-speed modeling of large-scale neural systems to real-time behaving systems, to bidirectional brain-machine interfaces. The specific circuit solutions used to implement silicon neurons depend on the application requirements. In this paper we describe the most common building blocks and techniques used to implement these circuits, and present an overview of a wide range of neuromorphic silicon neurons, which implement different computational models, ranging from biophysically realistic and conductance based Hodgkin-Huxley models to bi-dimensional generalized adaptive Integrate and Fire models. We compare the different design methodologies used for each silicon neuron design described, and demonstrate their features with experimental results, measured from a wide range of fabricated VLSI chips.

  15. The Cold Chain Logistics for Perishable Agricultural Products in China

    OpenAIRE

    Hou Yanfang; Xie Dong; Wang Jianbo

    2015-01-01

    This study introduces concepts of the agricultural product cold chain logistics and domestic and international researches. Also, the study discusses issues of Chinese agricultural cold chain logistics in the development process as the following aspects: the dividing of cold chain logistics market, refrigeration hardware facilities, third-party cold chain logistics development, the level of cold chain technologies, cold chain logistics professionals and the legal system and the standard system...

  16. Afferent neuronal control of type-I gonadotropin releasing hormone (GnRH neurons in the human

    Directory of Open Access Journals (Sweden)

    Erik eHrabovszky

    2013-09-01

    Full Text Available Understanding the regulation of the human menstrual cycle represents an important ultimate challenge of reproductive neuroendocrine research. However, direct translation of information from laboratory animal experiments to the human is often complicated by strikingly different and unique reproductive strategies and central regulatory mechanisms that can be present in even closely related animal species. In all mammals studied so far, type-I gonadotropin releasing hormone (GnRH synthesizing neurons form the final common output way from the hypothalamus in the neuroendocrine control of the adenohypophysis. Under various physiological and pathological conditions, hormonal and metabolic signals either regulate GnRH neurons directly or act on upstream neuronal circuitries to influence the pattern of pulsatile GnRH secretion into the hypophysial portal circulation. Neuronal afferents to GnRH cells convey important metabolic-, stress-, sex steroid-, lactational- and circadian signals to the reproductive axis, among other effects. This article gives an overview of the available neuroanatomical literature that described the afferent regulation of human GnRH neurons by peptidergic, monoaminergic and amino acidergic neuronal systems. Recent studies of human genetics provided evidence that central peptidergic signaling by kisspeptins and neurokinin B play particularly important roles in puberty onset and later, in the sex steroid-dependent feedback regulation of GnRH neurons. This review article places special emphasis on the topographic distribution, sexual dimorphism, aging-dependent neuroanatomical changes and plastic connectivity to GnRH neurons of the critically important human hypothalamic kisspeptin and neurokinin B systems.

  17. Biphasic Equilibrium Dialysis of Poly(N-Isopropyl Acrylamide Nanogels Synthesized at Decreased Temperatures for Targeted Delivery of Thermosensitive Bioactives

    Directory of Open Access Journals (Sweden)

    Witold Musial

    2013-01-01

    Full Text Available Hydrogel nanoparticles, referred to also as nanogels, are of special interest for medical and pharmaceutical applications. Due to small size in the range below the diameter of the capillaries, they are proposed as drug delivery carriers. The aim of the study was to estimate the influence of composition and reaction conditions during synthesis of poly-N-isopropyl acrylamide cross-linked by polyethylene glycol diacrylate on the purification rates of the polymer. Six types of thermosensitive nanogels were prepared by surfactant-free dispersion polymerization and assessed in terms of process yield, composition, and size at temperatures below and over volume phase temperature. During the diffusion of impurities, in the course of dialysis, assessed by the conductometric method, the remarkable influence of temperature and initiator concentration on the process was revealed. The release rates varied in the range between 9.63 · 10−2 and 1.39 · 10−1 h−1 in the first stage of the process, whereas in the second stage they were between 2.09 · 10−2 and 6.28 · 10−2 h−1. The evaluated time to obtain acceptable purity of the preparation was estimated to be in the range of 18 days. More detailed research should be directed towards the influence of the structure of obtained material on the purification process.

  18. Perception of foot temperature in young women with cold constitution: analysis of skin temperature and warm and cold sensation thresholds.

    Science.gov (United States)

    Sadakata, Mieko; Yamada, Yoshiaki

    2007-06-01

    To examine the disease state of cold constitution, physiological measurements of the foot were conducted by investigating thermal sensations under an environmental condition of 25 degrees C-26 degrees C (neutral temperature) in 29 young women with and without cold constitution. The subjects were classified into 3 groups according to their experiences with cold constitution: cold constitution, intermediate, and normal groups. Foot skin temperature was measured by thermography. Thermal sensations were measured on the dorsum of the left foot using a thermal stimulator. Cold and warm spots on the dorsum of the right foot were ascertained. Thermal stimulation was delivered by a copper probe. No significant differences in foot skin temperature among these 3 groups were identified as measured in a laboratory under neutral temperature conditions. However, the mean warm sensation threshold was +6.3+/-1.09 degrees C (mean+/-SEM) for the cold constitution group (n=14), +3.4+/-2.10 degrees C (mean+/-SEM) for the intermediate group (n=7), and -0.25+/-1.96 degrees C (mean+/-SEM) for the normal group (n=6). The difference was significant between the cold constitution and normal groups. No significant differences among the 3 groups were found in the cold sensation threshold. This may be attributable to the distribution of thermal receptors and to chronically reduced blood flow in subcutaneous tissues, where the skin temperature receptors responsible for temperature sensation are located.

  19. An empirical model for friction in cold forging

    DEFF Research Database (Denmark)

    Bay, Niels; Eriksen, Morten; Tan, Xincai

    2002-01-01

    With a system of simulative tribology tests for cold forging the friction stress for aluminum, steel and stainless steel provided with typical lubricants for cold forging has been determined for varying normal pressure, surface expansion, sliding length and tool/work piece interface temperature...... of normal pressure and tool/work piece interface temperature. The model is verified by process testing measuring friction at varying reductions in cold forward rod extrusion. KEY WORDS: empirical friction model, cold forging, simulative friction tests....

  20. A low-density culture method of cerebellar granule neurons with paracrine support applicable for the study of neuronal morphogenesis.

    Science.gov (United States)

    Kubota, Kenta; Seno, Takeshi; Konishi, Yoshiyuki

    2013-11-20

    Cerebellar granule neuronal cultures have been used to study the molecular mechanisms underlying neuronal functions, including neuronal morphogenesis. However, a limitation of this system is the difficulty to analyze isolated neurons because these are required to be maintained at a high density. Therefore, in the present study, we aimed to develop a simple and cost-effective method for culturing low-density cerebellar granule neurons. Cerebellar granule cells at two different densities (low- and high-density) were co-cultivated in order for the low-density culture to be supported by the paracrine signals from the high-density culture. This method enabled morphology analysis of isolated cerebellar granule neurons without astrocytic feeder cultures or supplements such as B27. Using this method, we investigated the function of a polarity factor. Studies using hippocampal neurons suggested that glycogen synthase kinase-3 (GSK-3) is an essential regulator of neuronal polarity, and inhibition of GSK-3 results in the formation of multiple axons. Pharmacological inhibitors for GSK-3 (6-bromoindirubin-3'-oxime and lithium chloride) did not cause the formation of multiple axons of cerebellar granule neurons but significantly reduced their length. Consistent results were obtained by introducing kinase-dead form of GSK-3 beta (K85A). These results indicated that GSK-3 is not directly involved in the control of neuronal polarity in cerebellar granule neurons. Overall, this study provides a simple method for culturing low-density cerebellar granule neurons and insights in to the neuronal-type dependent function of GSK-3 in neuronal morphogenesis. © 2013 Elsevier B.V. All rights reserved.

  1. Acute Cold / Restraint Stress in Castrated Rats

    Directory of Open Access Journals (Sweden)

    Farideh Zafari Zangeneh

    2008-09-01

    Full Text Available Objective: The present study aimed to determine whether castration altered osmotically stimulated vasopressin (VP release and urinary volume and what is the role of endocrine-stress axis in this process.Materials and methods: Totally 108 mice were studied in two main groups of castrated (n=78 and control (n=30. Each group was extracted by acute cold stress (4◦C for 2h/day, restraint stress (by syringes 60cc 2h/day and cold/restraint stress. The castrated group was treated in sub groups of testosterone, control (sesame oil as vehicle of testosterone. Propranolol as blocker of sympathetic nervous system was given to both groups of castrated mice and main control.Results: Our results showed that, there is interactions between testosterone and sympathetic nervous system on vasopressin, because urine volume was decreased only in testoctomized mice with cold/restraint and cold stress (P<0.001; propranolol as the antagonist of sympathetic nervous system could block and increase urine volume in castrated mice. This increased volume of urine was due to acute cold stress, not restraint stress (p<0.001. The role of testosterone, noradrenalin (NA and Vasopressin (VP in the acute cold stress is confirmed, because testosterone could return the effect of decreased urine volume in control group (P<0.001. Conclusion: Considering the effect of cold/restraint stress on urinary volume in castrated mice shows that there is interaction between sex hormone (testosterone, vasopressin and adrenergic systems.

  2. Reactor cold neutron source facility, the first in Japan

    International Nuclear Information System (INIS)

    Utsuro, Masahiko; Maeda, Yutaka; Kawai, Takeshi; Tashiro, Tameyoshi; Sakakibara, Shoji; Katada, Minoru.

    1986-01-01

    In the Research Reactor Institute, Kyoto University, the first cold neutron source facility for the reactor in Japan was installed, and various tests are carried out outside the reactor. Nippon Sanso K.K. had manufactured it. After the prescribed tests outside the reactor, this facility will be installed soon in the reactor, and its outline is described on this occasion. Cold neutrons are those having very small energy by being cooled to about-250 deg C. Since the wavelength of the material waves of cold neutrons is long, and their energy is small, they are very advantageous as an experimental means for clarifying the structure of living body molecules and polymers, the atom configuration in alloys, and atomic and molecular movements by neutron scattering and neutron diffraction. The basic principle of the cold neutron source facility is to irradiate thermal neutrons on a cold moderator kept around 20 K, and to moderate and cool the neutrons by nuclear scattering to convert to cold neutrons. The preparatory research on cold neutrons and hydrogen liquefaction, the basic design to put the cold neutron source facility in the graphite moderator facility, the safety countermeasures, the manufacture and quality control, the operation outside the reactor and the performance are reported. The cold neutron source facility comprises a cold moderator tank and other main parts, a deuterium gas tank, a helium refrigerator and instrumentation. (Kako, I.)

  3. Development of nondestructive measurement of cold work rate, (2)

    International Nuclear Information System (INIS)

    Kamimura, Hideaki; Igarashi, Miyuki; Satoh, Masakazu; Miura, Makoto

    1978-01-01

    Cold-worked type 316 stainless steel will be used as fuel cladding material for the proto-type fast reactor MONJU. Cold work rate is an important parameter in swelling behavior of fuel cladding. It has been shown that austenitic stainless steel undergoes martensitic transformation during cold working. Nondestructive evaluation of cold work rate will be expected by measuring residual magnetism produced in the presence of martensitic phase when cold worked austenitic stainless steel is magnetized. In the previous work, the residual magnetism of cladding tubes of type 316 stainless steel was measured. The results have shown high degree of the correlation between residual magnetism and cold work rate. This paper reports the results of measurement on cold-rolled type 316 stainless steel plate samples. Dimensions of the specimens are 100 mm long and 3.5 and 7 mm wide. The apparatus and experimental procedures were similar to the previous work. Good agreement was found between the estimated cold work rate obtained in the previous work and that for cold rolled plate specimens. Measurement of residual magnetism in identical direction with magnetization showed smaller dispersion of data as compared with that in transverse direction. The residual magnetism near specimen surface hardly decreased when the surface of specimen was chemically removed. The reason for the comparative decrease in residual magnetism at 10% and 15% cold work rate is not clear. (Wakatsuki, Y.)

  4. Perifornical orexinergic neurons modulate REM sleep by influencing locus coeruleus neurons in rats.

    Science.gov (United States)

    Choudhary, R C; Khanday, M A; Mitra, A; Mallick, B N

    2014-10-24

    Activation of the orexin (OX)-ergic neurons in the perifornical (PeF) area has been reported to induce waking and reduce rapid eye movement sleep (REMS). The activities of OX-ergic neurons are maximum during active waking and they progressively reduce during non-REMS (NREMS) and REMS. Apparently, the locus coeruleus (LC) neurons also behave in a comparable manner as that of the OX-ergic neurons particularly in relation to waking and REMS. Further, as PeF OX-ergic neurons send dense projections to LC, we argued that the former could drive the LC neurons to modulate waking and REMS. Studies in freely moving normally behaving animals where simultaneously neuro-chemo-anatomo-physio-behavioral information could be deciphered would significantly strengthen our understanding on the regulation of REMS. Therefore, in this study in freely behaving chronically prepared rats we stimulated the PeF neurons without or with simultaneous blocking of specific subtypes of OX-ergic receptors in the LC while electrophysiological recording characterizing sleep-waking was continued. Single dose of glutamate stimulation as well as sustained mild electrical stimulation of PeF (both bilateral) significantly increased waking and reduced REMS as compared to baseline. Simultaneous application of OX-receptor1 (OX1R) antagonist bilaterally into the LC prevented PeF stimulation-induced REMS suppression. Also, the effect of electrical stimulation of the PeF was long lasting as compared to that of the glutamate stimulation. Further, sustained electrical stimulation significantly decreased both REMS duration as well as REMS frequency, while glutamate stimulation decreased REMS duration only. Copyright © 2014 IBRO. Published by Elsevier Ltd. All rights reserved.

  5. The use of cold plasma generators in medicine

    Directory of Open Access Journals (Sweden)

    Kolomiiets R.O.

    2017-04-01

    Full Text Available Cold plasma treatment of wounds is a modern area of therapeutic medicine. We describe the physical mechanisms of cold plasma, the principles of therapeutic effects and design of two common types of cold plasma generators for medical use. This work aims at disclosing the basic principles of construction of cold atmospheric plasma generators in medicine and prospects for their further improvement. The purpose of this work is to improve the existing cold atmospheric plasma generators for use in medical applications. Novelty of this work consists in the application of new principles of construction of cold atmospheric plasmas medical apparatus, namely the combination of the gas discharge chamber, electrodes complex shape forming device and plasma flow in a single package. This helps to achieve a significant reduction in the size of the device, and a discharge chamber design change increases the therapeutic effect. The design of cold atmospheric plasma generator type «pin-to-hole», which is able to control parameters using the plasma current (modulation fluctuations in the primary winding and mechanically (using optional rotary electrode. It is also possible to combine some similar generators in the set, which will increase the surface area of the plasma treatment. We consider the basic principles of generating low atmospheric plasma flow, especially the formation of the plasma jet, changing its shape and modulation stream. The features of cold plasma generator design and information about prospects for further application, and opportunities for further improvement are revealed. The recommendations for further use of cold atmospheric plasma generators in medicine are formulated.

  6. The mirror neuron system.

    Science.gov (United States)

    Cattaneo, Luigi; Rizzolatti, Giacomo

    2009-05-01

    Mirror neurons are a class of neurons, originally discovered in the premotor cortex of monkeys, that discharge both when individuals perform a given motor act and when they observe others perform that same motor act. Ample evidence demonstrates the existence of a cortical network with the properties of mirror neurons (mirror system) in humans. The human mirror system is involved in understanding others' actions and their intentions behind them, and it underlies mechanisms of observational learning. Herein, we will discuss the clinical implications of the mirror system.

  7. Intraspecies differences in cold hardiness, carbohydrate content and β-amylase gene expression of Vaccinium corymbosum during cold acclimation and deacclimation.

    Science.gov (United States)

    Lee, Jun Hyung; Yu, Duk Jun; Kim, Su Jin; Choi, Doil; Lee, Hee Jae

    2012-12-01

    Changes in cold hardiness, carbohydrate content and β-amylase gene expression were monitored in the shoots of the highbush blueberry (Vaccinium corymbosum L.) cultivars 'Sharpblue' and 'Jersey' during cold acclimation (CA) and deacclimation (DA). The seasonal patterns were similar in both cultivars, but the levels of cold hardiness determined by electrolyte leakage analysis were significantly different; 'Jersey' was hardier than 'Sharpblue'. Cold hardiness was closely related to total soluble sugar content (r = -0.98** and -0.99** for 'Sharpblue' and 'Jersey', respectively). In 'Jersey', more soluble sugars accumulated during CA. Of the detected soluble sugars, glucose, fructose and raffinose contents were significantly associated with cold hardiness in both cultivars. Sucrose was abundant in both cultivars, and stachyose content changed significantly during CA and DA. However, they were not associated with cold hardiness. A sharp decrease in starch contents in the middle of CA coincided with β-amylase gene (VcBMY) expression, indicating the conversion of starch into soluble sugars. During CA, VcBMY was expressed up to twofold higher in 'Jersey' than in 'Sharpblue'. These results suggest that intraspecies differences in the cold hardiness of highbush blueberries are associated with total soluble sugar content, which is driven partly by differential expression of VcBMY.

  8. How to make spinal motor neurons.

    Science.gov (United States)

    Davis-Dusenbery, Brandi N; Williams, Luis A; Klim, Joseph R; Eggan, Kevin

    2014-02-01

    All muscle movements, including breathing, walking, and fine motor skills rely on the function of the spinal motor neuron to transmit signals from the brain to individual muscle groups. Loss of spinal motor neuron function underlies several neurological disorders for which treatment has been hampered by the inability to obtain sufficient quantities of primary motor neurons to perform mechanistic studies or drug screens. Progress towards overcoming this challenge has been achieved through the synthesis of developmental biology paradigms and advances in stem cell and reprogramming technology, which allow the production of motor neurons in vitro. In this Primer, we discuss how the logic of spinal motor neuron development has been applied to allow generation of motor neurons either from pluripotent stem cells by directed differentiation and transcriptional programming, or from somatic cells by direct lineage conversion. Finally, we discuss methods to evaluate the molecular and functional properties of motor neurons generated through each of these techniques.

  9. Firing dynamics of an autaptic neuron

    International Nuclear Information System (INIS)

    Wang Heng-Tong; Chen Yong

    2015-01-01

    Autapses are synapses that connect a neuron to itself in the nervous system. Previously, both experimental and theoretical studies have demonstrated that autaptic connections in the nervous system have a significant physiological function. Autapses in nature provide self-delayed feedback, thus introducing an additional timescale to neuronal activities and causing many dynamic behaviors in neurons. Recently, theoretical studies have revealed that an autapse provides a control option for adjusting the response of a neuron: e.g., an autaptic connection can cause the electrical activities of the Hindmarsh–Rose neuron to switch between quiescent, periodic, and chaotic firing patterns; an autapse can enhance or suppress the mode-locking status of a neuron injected with sinusoidal current; and the firing frequency and interspike interval distributions of the response spike train can also be modified by the autapse. In this paper, we review recent studies that showed how an autapse affects the response of a single neuron. (topical review)

  10. The Combined Effect of Cold and Moisture on Manual Performance.

    Science.gov (United States)

    Ray, Matthew; Sanli, Elizabeth; Brown, Robert; Ennis, Kerri Ann; Carnahan, Heather

    2018-02-01

    Objective The aim of this study was to investigate the combined effect of cold and moisture on manual performance and tactile sensitivity. Background People working in the ocean environment often perform manual work in cold and wet conditions. Although the independent effects of cold and moisture on hand function are known, their combined effect has not been investigated. Method Participants completed sensory (Touch-Test, two-point discrimination) and motor (Purdue Pegboard, Grooved Pegboard, reef knot untying) tests in the following conditions: dry hand, wet hand, cold hand, and cold and wet hand. Results For the Purdue Pegboard and knot untying tasks, the greatest decrement in performance was observed in the cold-and-wet-hand condition, whereas the decrements seen in the cold-hand and wet-hand conditions were similar. In the Grooved Pegboard task, the performance decrements exhibited in the cold-and-wet-hand condition and the cold-hand condition were similar, whereas no decrement was observed in the wet-hand condition. Tactile sensitivity was reduced in the cold conditions for the Touch-Test but not the two-point discrimination test. The combined effect of cold and moisture led to the largest performance decrements except when intrinsic object properties helped with grasp maintenance. The independent effects of cold and moisture on manual performance were comparable. Application Tools and equipment for use in the cold ocean environment should be designed to minimize the effects of cold and moisture on manual performance by including object properties that enhance grasp maintenance and minimize the fine-dexterity requirements.

  11. Heat shock protection against cold stress of Drosophila melanogaster

    OpenAIRE

    Burton, Vicky; Mitchell, Herschel K.; Young, Patricia; Petersen, Nancy S.

    1988-01-01

    Heat shock protein synthesis can be induced during recovery from cold treatment of Drosophila melanogaster larvae. Survival of larvae after a cold treatment is dramatically improved by a mild heat shock just before the cold shock. The conditions which induce tolerance to cold are similar to those which confer tolerance to heat.

  12. Expert Cold Structure Development

    Science.gov (United States)

    Atkins, T.; Demuysere, P.

    2011-05-01

    The EXPERT Program is funded by ESA. The objective of the EXPERT mission is to perform a sub-orbital flight during which measurements of critical aero- thermodynamic phenomena will be obtained by using state-of-the-art instrumentation. As part of the EXPERT Flight Segment, the responsibility of the Cold Structure Development Design, Manufacturing and Validation was committed to the Belgian industrial team SONACA/SABCA. The EXPERT Cold Structure includes the Launcher Adapter, the Bottom Panel, the Upper Panel, two Cross Panels and the Parachute Bay. An additional Launcher Adapter was manufactured for the separation tests. The selected assembly definition and manufacturing technologies ( machined parts and sandwich panels) were dictated classically by the mass and stiffness, but also by the CoG location and the sensitive separation interface. Used as support for the various on-board equipment, the Cold Structure is fixed to but thermally uncoupled from the PM 1000 thermal shield. It is protect on its bottom panel by a thermal blanket. As it is a protoflight, analysis was the main tool for the verification. Low level stiffness and modal analysis tests have also been performed on the Cold Structure equipped with its ballast. It allowed to complete its qualification and to prepare SONACA/SABCA support for the system dynamic tests foreseen in 2011. The structure was finally coated with a thermal control black painting and delivered on time to Thales Alenia Space-Italy end of March 201.

  13. Mirror neurons: functions, mechanisms and models.

    Science.gov (United States)

    Oztop, Erhan; Kawato, Mitsuo; Arbib, Michael A

    2013-04-12

    Mirror neurons for manipulation fire both when the animal manipulates an object in a specific way and when it sees another animal (or the experimenter) perform an action that is more or less similar. Such neurons were originally found in macaque monkeys, in the ventral premotor cortex, area F5 and later also in the inferior parietal lobule. Recent neuroimaging data indicate that the adult human brain is endowed with a "mirror neuron system," putatively containing mirror neurons and other neurons, for matching the observation and execution of actions. Mirror neurons may serve action recognition in monkeys as well as humans, whereas their putative role in imitation and language may be realized in human but not in monkey. This article shows the important role of computational models in providing sufficient and causal explanations for the observed phenomena involving mirror systems and the learning processes which form them, and underlines the need for additional circuitry to lift up the monkey mirror neuron circuit to sustain the posited cognitive functions attributed to the human mirror neuron system. Copyright © 2012 Elsevier Ireland Ltd. All rights reserved.

  14. Where do mirror neurons come from?

    Science.gov (United States)

    Heyes, Cecilia

    2010-03-01

    Debates about the evolution of the 'mirror neuron system' imply that it is an adaptation for action understanding. Alternatively, mirror neurons may be a byproduct of associative learning. Here I argue that the adaptation and associative hypotheses both offer plausible accounts of the origin of mirror neurons, but the associative hypothesis has three advantages. First, it provides a straightforward, testable explanation for the differences between monkeys and humans that have led some researchers to question the existence of a mirror neuron system. Second, it is consistent with emerging evidence that mirror neurons contribute to a range of social cognitive functions, but do not play a dominant, specialised role in action understanding. Finally, the associative hypothesis is supported by recent data showing that, even in adulthood, the mirror neuron system can be transformed by sensorimotor learning. The associative account implies that mirror neurons come from sensorimotor experience, and that much of this experience is obtained through interaction with others. Therefore, if the associative account is correct, the mirror neuron system is a product, as well as a process, of social interaction. (c) 2009 Elsevier Ltd. All rights reserved.

  15. Cold versus hot fusion deuterium branching ratios

    International Nuclear Information System (INIS)

    Fox, H.; Bass, R.

    1995-01-01

    A major source of misunderstanding of the nature of cold nuclear fusion has been the expectation that the deuterium branching ratios occurring within a palladium lattice would be consistent with the gas-plasma branching ratios. This misunderstanding has led to the concept of the dead graduate student, the 1989's feverish but fruitless search for neutron emissions from cold fusion reactors, and the follow-on condemnation of the new science of cold fusion. The experimental facts are that in a properly loaded palladium lattice, the deuterium fusion produces neutrons at little above background, a greatly less-than-expected production of tritium (the tritium desert), and substantially more helium-4 than is observed in hot plasma physics. The experimental evidence is now compelling (800 reports of success from 30 countries) that cold nuclear fusion is a reality, that the branching ratios are unexpected, and that a new science is struggling to be recognized. Commercialization of some types of cold fusion devices has already begun

  16. Improving cold chain systems: Challenges and solutions.

    Science.gov (United States)

    Ashok, Ashvin; Brison, Michael; LeTallec, Yann

    2017-04-19

    While a number of new vaccines have been rolled out across the developing world (with more vaccines in the pipeline), cold chain systems are struggling to efficiently support national immunization programs in ensuring the availability of safe and potent vaccines. This article reflects on the Clinton Health Access Initiative, Inc. (CHAI) experience working since 2010 with national immunization programs and partners to improve vaccines cold chains in 10 countries-Ethiopia, Nigeria, Kenya, Malawi, Tanzania, Uganda, Cameroon, Mozambique, Lesotho and India - to identify the root causes and solutions for three common issues limiting cold chain performance. Key recommendations include: Collectively, the solutions detailed in this article chart a path to substantially improving the performance of the cold chain. Combined with an enabling global and in-country environment, it is possible to eliminate cold chain issues as a substantial barrier to effective and full immunization coverage over the next few years. Copyright © 2017. Published by Elsevier Ltd.

  17. Temporary targeted renal blood flow interruption using a reverse thermosensitive polymer to facilitate bloodless partial nephrectomy: a swine survival study.

    Science.gov (United States)

    Harty, Niall J; Laskey, Daniel H; Moinzadeh, Alireza; Flacke, Sebastian; Benn, James A; Villani, Rosanna; Kalra, Aarti; Libertino, John A; Madras, Peter N

    2012-09-01

    What's known on the subject? and What does the study add? Lumagel™ is a reverse thermosensitive polymer (RTP) that has previously been described in the literature as providing temporary vascular occlusion to allow for bloodless partial nephrectomy (PN) while maintaining blood flow to the untargeted portion of the kidney. At body temperature, Lumagel™ has the consistency of a viscous gel but upon cooling rapidly converts to a liquid state and does not reconstitute thereafter. This property has allowed for it to be used in situations requiring temporary vascular occlusion. Previous experience with similar RTPs in coronary arteries proved successful, with no detectable adverse events. We have previously described our technique for temporary vascular occlusion of the main renal artery, as well as segmental and sub-segmental renal branches, to allow for bloodless PN in either an open or minimally invasive approach. These experiments were performed in the acute setting. This study is a two-armed survival trial to assess whether this RTP is as safe as hilar clamping for bloodless PN. Surviving animals showed normal growth after using the RTP, absence of toxicity, no organ dysfunction, and no pathological changes attributable to the RTP. We conclude that Lumagel™ is as safe as conventional PN with hilar clamping, while adding the advantage of uninterrupted perfusion during renal resection. To examine whether randomly selected regions of the kidney could undergo temporary flow interruption with a reverse thermosensitive polymer (RTP), Lumagel™ (Pluromed, Inc., Woburn, MA, USA), followed by partial nephrectomy (PN), without adding risks beyond those encountered in the same procedure with the use of hilar clamping. A two-armed (RTP vs hilar clamp), 6-week swine survival study was performed. Four swine underwent PN using hilar clamps, while six underwent PN with flow interruption using the RTP. The RTP, administered angiographically, was used for intraluminal occlusion

  18. Combining Maize Base Germplasm for Cold Tolerance Breeding

    OpenAIRE

    Rodríguez Graña, Víctor Manuel; Butrón Gómez, Ana María; Sandoya Miranda, Germán; Ordás Pérez, Amando; Revilla Temiño, Pedro

    2007-01-01

    Early planting can contribute to increased grain yield of maize (Zea mays L.), but it requires cold tolerance. A limited number of cold-tolerant maize genotypes have been reported. The objectives of this study were to test a new strategy to improve cold tolerance in maize searching for broad x narrow genetic combinations that may be useful as base populations for breeding programs, to compare genotype performance under cold-controlled and field conditions, and to establish the major genetic e...

  19. Cold stress induces lower urinary tract symptoms.

    Science.gov (United States)

    Imamura, Tetsuya; Ishizuka, Osamu; Nishizawa, Osamu

    2013-07-01

    Cold stress as a result of whole-body cooling at low environmental temperatures exacerbates lower urinary tract symptoms, such as urinary urgency, nocturia and residual urine. We established a model system using healthy conscious rats to explore the mechanisms of cold stress-induced detrusor overactivity. In this review, we summarize the basic findings shown by this model. Rats that were quickly transferred from room temperature (27 ± 2°C) to low temperature (4 ± 2°C) showed detrusor overactivity including increased basal pressure and decreased voiding interval, micturition volume, and bladder capacity. The cold stress-induced detrusor overactivity is mediated through a resiniferatoxin-sensitve C-fiber sensory nerve pathway involving α1-adrenergic receptors. Transient receptor potential melastatin 8 channels, which are sensitive to thermal changes below 25-28°C, also play an important role in mediating the cold stress responses. Additionally, the sympathetic nervous system is associated with transient hypertension and decreases of skin surface temperature that are closely correlated with the detrusor overactivity. With this cold stress model, we showed that α1-adrenergic receptor antagonists have the potential to treat cold stress-exacerbated lower urinary tract symptoms. In addition, we showed that traditional Japanese herbal mixtures composed of Hachimijiogan act, in part, by increasing skin temperature and reducing the number of cold sensitive transient receptor potential melastatin channels in the skin. The effects of herbal mixtures have the potential to treat and/or prevent the exacerbation of lower urinary tract symptoms by providing resistance to the cold stress responses. Our model provides new opportunities for utilizing animal disease models with altered lower urinary tract functions to explore the effects of novel therapeutic drugs. © 2013 The Japanese Urological Association.

  20. A novel combination technique of cold crystalloid perfusion but not cold storage facilitates transplantation of canine hearts donated after circulatory death.

    Science.gov (United States)

    Rosenfeldt, Franklin; Ou, Ruchong; Salamonsen, Robert; Marasco, Silvana; Zimmet, Adam; Byrne, Joshua; Cosic, Filip; Saxena, Pankaj; Esmore, Donald

    2016-11-01

    Donation after circulatory death (DCD) represents a potential new source of hearts to increase the donor pool. We showed previously that DCD hearts in Greyhound dogs could be resuscitated and preserved by continuous cold crystalloid perfusion but not by cold static storage and could demonstrate excellent contractile and metabolic function on an in vitro system. In the current study, we demonstrate that resuscitated DCD hearts are transplantable. Donor Greyhound dogs (n = 12) were divided into perfusion (n = 8) and cold static storage (n = 4) groups. General anesthesia was induced and ventilation ceased for 30 minutes to achieve circulatory death. Donor cardiectomy was performed, and for 4 hours the heart was preserved by controlled reperfusion, followed by continuous cold perfusion with an oxygenated crystalloid perfusate or by static cold storage, after which orthotopic heart transplantation was performed. Recovery was assessed over 4 hours by hemodynamic monitoring. During cold perfusion, hearts showed continuous oxygen consumption and low lactate levels, indicating aerobic metabolism. The 8 dogs in the perfusion group were weaned off bypass, and 4 hours after bypass produced cardiac output of 4.73 ± 0.51 liters/min, left ventricular power of 7.63 ± 1.32 J/s, right ventricular power of 1.40 ± 0.43 J/s, and left ventricular fractional area shortening of 39.1% ± 5.2%, all comparable to pre-transplant values. In the cold storage group, 3 of 4 animals could not be weaned from cardiopulmonary bypass, and the fourth exhibited low-level function. Cold crystalloid perfusion, but not cold static storage, can resuscitate and preserve the DCD donor heart in a canine model of heart transplantation, thus rendering it transplantable. Controlled reperfusion and cold crystalloid perfusion have potential for clinical application in DCD transplantation. Copyright © 2016. Published by Elsevier Inc.

  1. Mirror neurons: from origin to function.

    Science.gov (United States)

    Cook, Richard; Bird, Geoffrey; Catmur, Caroline; Press, Clare; Heyes, Cecilia

    2014-04-01

    This article argues that mirror neurons originate in sensorimotor associative learning and therefore a new approach is needed to investigate their functions. Mirror neurons were discovered about 20 years ago in the monkey brain, and there is now evidence that they are also present in the human brain. The intriguing feature of many mirror neurons is that they fire not only when the animal is performing an action, such as grasping an object using a power grip, but also when the animal passively observes a similar action performed by another agent. It is widely believed that mirror neurons are a genetic adaptation for action understanding; that they were designed by evolution to fulfill a specific socio-cognitive function. In contrast, we argue that mirror neurons are forged by domain-general processes of associative learning in the course of individual development, and, although they may have psychological functions, they do not necessarily have a specific evolutionary purpose or adaptive function. The evidence supporting this view shows that (1) mirror neurons do not consistently encode action "goals"; (2) the contingency- and context-sensitive nature of associative learning explains the full range of mirror neuron properties; (3) human infants receive enough sensorimotor experience to support associative learning of mirror neurons ("wealth of the stimulus"); and (4) mirror neurons can be changed in radical ways by sensorimotor training. The associative account implies that reliable information about the function of mirror neurons can be obtained only by research based on developmental history, system-level theory, and careful experimentation.

  2. Evaluation of a novel biodegradable thermosensitive keto-hydrogel for improving postoperative pain in a rat model.

    Science.gov (United States)

    Wu, Meng-Huang; Shih, Ming-Hung; Hsu, Wei-Bin; Dubey, Navneet Kumar; Lee, Wen-Fu; Lin, Tsai-Yu; Hsieh, Meng-Yow; Chen, Chin-Fu; Peng, Kuo-Ti; Huang, Tsung-Jen; Shi, Chung-Sheng; Guo, Ren-Shyang; Cai, Chang-Jhih; Chung, Chiu-Yen; Wong, Chung-Hang

    2017-01-01

    This study evaluates the sustained analgesic effect of ketorolac-eluting thermosensitive biodegradable hydrogel in the plantar incisional pain model of the rat hind-paw. A ketorolac-embedded 2, 2'-Bis (2-oxazolin) (BOX) linking methoxy-poly(ethylene glycol) and poly(lactide-co-glycolide) (mPEG-PLGA) diblock copolymer (BOX copolymer) was synthesized as keto-hydrogel based on optimal sol-gel phase transition and in vitro drug release profile. The effect of keto-hydrogel on postoperative pain (POP) was assessed using the established plantar incisional pain model in hind-paw of rats and compared to that of ketorolac solution. Pain and sensory threshold, as well as pain scoring, were evaluated with behavioral tests by means of anesthesiometer and incapacitance apparatus, respectively. Pro-inflammatory cytokine levels (TNF-α, IL-6, VEGF, and IL-1β) around incisional wounds were measured by ELISA. Tissue histology was assessed using hematoxylin and eosin and Masson's trichrome staining. Ten mg/mL (25 wt%) keto-hydrogel showed a sol-gel transition at 26.4°C with a 10-day sustained drug release profile in vitro. Compared to ketorolac solution group, the concentration of ketorolac in tissue fluid was higher in the keto-hydrogel group during the first 18 h of application. Keto-hydrogel elevated pain and sensory threshold, increased weight-bearing capacity, and significantly reduced the levels of TNF-α, IL-6, and IL-1β while enhanced VEGF in tissue fluid. Histologic analysis reveals greater epithelialization and collagen deposition around wound treated with keto-hydrogel. In conclusion, our study suggests that keto-hydrogel is an ideal compound to treat POP with a secondary gain of improved incisional wound healing.

  3. Evaluation of a novel biodegradable thermosensitive keto-hydrogel for improving postoperative pain in a rat model.

    Directory of Open Access Journals (Sweden)

    Meng-Huang Wu

    Full Text Available This study evaluates the sustained analgesic effect of ketorolac-eluting thermosensitive biodegradable hydrogel in the plantar incisional pain model of the rat hind-paw. A ketorolac-embedded 2, 2'-Bis (2-oxazolin (BOX linking methoxy-poly(ethylene glycol and poly(lactide-co-glycolide (mPEG-PLGA diblock copolymer (BOX copolymer was synthesized as keto-hydrogel based on optimal sol-gel phase transition and in vitro drug release profile. The effect of keto-hydrogel on postoperative pain (POP was assessed using the established plantar incisional pain model in hind-paw of rats and compared to that of ketorolac solution. Pain and sensory threshold, as well as pain scoring, were evaluated with behavioral tests by means of anesthesiometer and incapacitance apparatus, respectively. Pro-inflammatory cytokine levels (TNF-α, IL-6, VEGF, and IL-1β around incisional wounds were measured by ELISA. Tissue histology was assessed using hematoxylin and eosin and Masson's trichrome staining. Ten mg/mL (25 wt% keto-hydrogel showed a sol-gel transition at 26.4°C with a 10-day sustained drug release profile in vitro. Compared to ketorolac solution group, the concentration of ketorolac in tissue fluid was higher in the keto-hydrogel group during the first 18 h of application. Keto-hydrogel elevated pain and sensory threshold, increased weight-bearing capacity, and significantly reduced the levels of TNF-α, IL-6, and IL-1β while enhanced VEGF in tissue fluid. Histologic analysis reveals greater epithelialization and collagen deposition around wound treated with keto-hydrogel. In conclusion, our study suggests that keto-hydrogel is an ideal compound to treat POP with a secondary gain of improved incisional wound healing.

  4. A PLGA-PEG-PLGA Thermosensitive Gel Enabling Sustained Delivery of Ropivacaine Hydrochloride for Postoperative Pain Relief.

    Science.gov (United States)

    Fu, Xudong; Zeng, Huilin; Guo, Jiaping; Liu, Hong; Shi, Zhen; Chen, Huhai; Li, Dezong; Xie, Xiangyang; Kuang, Changchun

    2017-01-01

    Postoperative pain is a complex physiological response to disease and tissue injury. Moderate-to-severe pain typically occurs within 48 h after surgery. Amino amide local anesthetics are widely applied to manage postoperative pain, and they have high efficacy, a low risk for addiction and limited side effects. However, these anesthetics also have short half-lives, often necessitating continuous injection to obtain satisfactory pain relief. In the current work, we used a poly(lactic-co-glycolic acid) (PLGA)-polyethylene glycol (PEG)-PLGA (PLGA-PEG-PLGA) temperature-sensitive gel to deliver a local anesthetic, ropivacaine hydrochloride (RP), to prolong its analgesic effect. We investigated the influence of polymer and drug concentration on gelation temperature and the in vitro drug release rate from the temperature-sensitive gel. RP-loaded PLGA-PEG-PLGA solution is a liquid at room temperature and forms a gel at temperatures slightly lower than body temperature. With regard to the gel's drug release rate, 37.5, 51.3 and 72.6% of RP was released at 12, 24 and 48 h, respectively. This in vitro drug release profile conformed to the Higuchi equation. To assess pain control efficacy when using the gel, we evaluated the mechanical paw withdrawal reflex threshold, thermal pain threshold and incision cumulative pain scores in a rat incisional model. The results showed that the anti-pain effect of a single injection of RP-loaded gel at the incision site lasted for 48 h, which is significantly longer than the effect produced by injection of RP solution alone. The use of RP-loaded thermosensitive gels could provide a promising method for managing postoperative pain.

  5. A novel behavioral assay for measuring cold sensation in mice.

    Science.gov (United States)

    Brenner, Daniel S; Golden, Judith P; Gereau, Robert W

    2012-01-01

    Behavioral models of cold responses are important tools for exploring the molecular mechanisms of cold sensation. To complement the currently cold behavioral assays and allow further studies of these mechanisms, we have developed a new technique to measure the cold response threshold, the cold plantar assay. In this assay, animals are acclimated on a glass plate and a cold stimulus is applied to the hindpaw through the glass using a pellet of compressed dry ice. The latency to withdrawal from the cooled glass is used as a measure of the cold response threshold of the rodents, and the dry ice pellet provides a ramping cold stimulus on the glass that allows the correlation of withdrawal latency values to rough estimates of the cold response threshold temperature. The assay is highly sensitive to manipulations including morphine-induced analgesia, Complete Freund's Adjuvant-induced inflammatory allodynia, and Spinal Nerve Ligation-induced neuropathic allodynia.

  6. High-Degree Neurons Feed Cortical Computations.

    Directory of Open Access Journals (Sweden)

    Nicholas M Timme

    2016-05-01

    Full Text Available Recent work has shown that functional connectivity among cortical neurons is highly varied, with a small percentage of neurons having many more connections than others. Also, recent theoretical developments now make it possible to quantify how neurons modify information from the connections they receive. Therefore, it is now possible to investigate how information modification, or computation, depends on the number of connections a neuron receives (in-degree or sends out (out-degree. To do this, we recorded the simultaneous spiking activity of hundreds of neurons in cortico-hippocampal slice cultures using a high-density 512-electrode array. This preparation and recording method combination produced large numbers of neurons recorded at temporal and spatial resolutions that are not currently available in any in vivo recording system. We utilized transfer entropy (a well-established method for detecting linear and nonlinear interactions in time series and the partial information decomposition (a powerful, recently developed tool for dissecting multivariate information processing into distinct parts to quantify computation between neurons where information flows converged. We found that computations did not occur equally in all neurons throughout the networks. Surprisingly, neurons that computed large amounts of information tended to receive connections from high out-degree neurons. However, the in-degree of a neuron was not related to the amount of information it computed. To gain insight into these findings, we developed a simple feedforward network model. We found that a degree-modified Hebbian wiring rule best reproduced the pattern of computation and degree correlation results seen in the real data. Interestingly, this rule also maximized signal propagation in the presence of network-wide correlations, suggesting a mechanism by which cortex could deal with common random background input. These are the first results to show that the extent to

  7. Cryogenic refrigeration for cold neutron sources

    International Nuclear Information System (INIS)

    Gistau-Baguer, Guy

    1998-01-01

    Neutron moderation by means of a fluid at cryogenic temperature is a very interesting way to obtain cold neutrons. Today, a number of nuclear research reactors are using this technology. This paper deals with thermodynamics and technology which are used for cooling Cold Neutron Sources

  8. Development of thermosensitive poly(n-isopropylacrylamide-co-((2-dimethylamino) ethyl methacrylate))-based nanoparticles for controlled drug release

    Energy Technology Data Exchange (ETDEWEB)

    Peng, Cheng-Liang; Luo, Tsai-Yueh; Lin, Wuu-Jyh [Isotope Application Division, Institute of Nuclear Energy Research, PO Box 3-27, Longtan Taoyuan 325, Taiwan (China); Tsai, Han-Min; Yang, Shu-Jyuan; Lin, Chia-Fu; Shieh, Ming-Jium, E-mail: soloman@ntu.edu.tw [Institute of Biomedical Engineering, College of Medicine and College of Engineering, National Taiwan University, No 1, Section 1, Jen-Ai Road, Taipei 10051, Taiwan (China)

    2011-07-01

    Thermosensitive nanoparticles based on poly(N-isopropylacrylamide-co-((2-dimethylamino)ethylmethacrylate)) (poly(NIPA-co-DMAEMA)) copolymers were successfully fabricated by free radical polymerization. The lower critical solution temperature (LCST) of the synthesized nanoparticles was 41 deg. C and a temperature above which would cause the nanoparticles to undergo a volume phase transition from 140 to 100 nm, which could result in the expulsion of encapsulated drugs. Therefore, we used the poly(NIPA-co-DMAEMA) nanoparticles as a carrier for the controlled release of a hydrophobic anticancer agent, 7-ethyl-10-hydroxy-camptothecin (SN-38). The encapsulation efficiency and loading content of SN-38-loaded nanoparticles at an SN-38/poly(NIPA-co-DMAEMA) ratio of 1/10 (D/P = 1/10) were about 80% and 6.293%, respectively. Moreover, the release profile of SN-38-loaded nanoparticles revealed that the release rate at 42 deg. C (above LCST) was higher than that at 37 deg. C (below LCST), which demonstrated that the release of SN-38 could be controlled by increasing the temperature. The cytotoxicity of the SN-38-loaded poly(NIPA-co-DMAEMA) nanoparticles was investigated in human colon cancer cells (HT-29) to compare with the treatment of an anticancer drug, Irinotecan (CPT-11). The antitumor efficacy evaluated in a C26 murine colon tumor model showed that the SN-38-loaded nanoparticles in combination with hyperthermia therapy efficiently suppressed tumor growth. The results indicate that these thermo-responsive nanoparticles are potential carriers for controlled drug delivery.

  9. On the number of preganglionic neurones driving human postganglionic sympathetic neurones: a comparison of modelling and empirical data

    Directory of Open Access Journals (Sweden)

    Vaughan G Macefield

    2011-12-01

    Full Text Available Postganglionic sympathetic axons in awake healthy human subjects, regardless of their identity as muscle vasoconstrictor, cutaneous vasoconstrictor or sudomotor neurones, discharge with a low firing probability (~30%, generate low firing rates (~0.5 Hz and typically fire only once per cardiac interval. The purpose of the present study was to use modelling of spike trains in an attempt to define the number of preganglionic neurones that drive an individual postganglionic neurone. Artificial spike trains were generated in 1-3 preganglionic neurones converging onto a single postganglionic neurone. Each preganglionic input fired with a mean interval distribution of either 1000, 1500, 2000, 2500 or 3000 ms and the standard deviation varied between 0.5, 1.0 and 2.0 x the mean interval; the discharge frequency of each preganglionic neurone exhibited positive skewness and kurtosis. Of the 45 patterns examined, the mean discharge properties of the postganglionic neurone could only be explained by it being driven by, on average, two preganglionic neurones firing with a mean interspike interval of 2500 ms and SD of 5000 ms. The mean firing rate resulting from this pattern was 0.22 Hz, comparable to that of spontaneously active muscle vasoconstrictor neurones in healthy subjects (0.40 Hz. Likewise, the distribution of the number of spikes per cardiac interval was similar between the modelled and actual data: 0 spikes (69.5 vs 66.6 %, 1 spike (25.6 vs 21.2 %, 2 spikes (4.3 vs 6.4 %, 3 spikes (0.5 vs 1.7 % and 4 spikes (0.1 vs 0.7 %. Although some features of the firing patterns could be explained by the postganglionic neurone being driven by a single preganglionic neurone, none of the emulated firing patterns generated by the firing of three preganglionic neurones matched the discharge of the real neurones. These modelling data indicate that, on average, human postganglionic sympathetic neurones are driven by two preganglionic inputs.

  10. Cold valleys in fusion and fission

    International Nuclear Information System (INIS)

    Misicu, S.

    2003-01-01

    The cold fission configuration after the preformation of the fragments resembles a short-lived dinuclear or quasi-molecular system. The most conceivable scission configuration is given by two fission fragments in touching with the symmetry axes aligned (pole-pole orientation). This conclusion was based on the simple argument that this configuration offers the optimal tunneling time, i.e. the difference between the Coulomb barrier and the decay energy Q is minimal. Other orientations are apparently precluded in cold spontaneous fission and should be regarded as quasi-fission doorways in the synthesis of superheavy elements by cold fusion. (orig.)

  11. Human Physiological Responses to Acute and Chronic Cold Exposure

    Science.gov (United States)

    Stocks, Jodie M.; Taylor, Nigel A. S.; Tipton, Michael J.; Greenleaf, John E.

    2001-01-01

    When inadequately protected humans are exposed to acute cold, excessive body heat is lost to the environment and unless heat production is increased and heat loss attenuated, body temperature will decrease. The primary physiological responses to counter the reduction in body temperature include marked cutaneous vasoconstriction and increased metabolism. These responses, and the hazards associated with such exposure, are mediated by a number of factors which contribute to heat production and loss. These include the severity and duration of the cold stimulus; exercise intensity; the magnitude of the metabolic response; and individual characteristics such as body composition, age, and gender. Chronic exposure to a cold environment, both natural and artificial, results in physiological alterations leading to adaptation. Three quite different, but not necessarily exclusive, patterns of human cold adaptation have been reported: metabolic, hypothermic, and insulative. Cold adaptation has also been associated with an habituation response, in which there is a desensitization, or damping, of the normal response to a cold stress. This review provides a comprehensive analysis of the human physiological and pathological responses to cold exposure. Particular attention is directed to the factors contributing to heat production and heat loss during acute cold stress, and the ability of humans to adapt to cold environments.

  12. Studies and modeling of cold neutron sources

    International Nuclear Information System (INIS)

    Campioni, G.

    2004-11-01

    With the purpose of updating knowledge in the fields of cold neutron sources, the work of this thesis has been run according to the 3 following axes. First, the gathering of specific information forming the materials of this work. This set of knowledge covers the following fields: cold neutron, cross-sections for the different cold moderators, flux slowing down, different measurements of the cold flux and finally, issues in the thermal analysis of the problem. Secondly, the study and development of suitable computation tools. After an analysis of the problem, several tools have been planed, implemented and tested in the 3-dimensional radiation transport code Tripoli-4. In particular, a module of uncoupling, integrated in the official version of Tripoli-4, can perform Monte-Carlo parametric studies with a spare factor of Cpu time fetching 50 times. A module of coupling, simulating neutron guides, has also been developed and implemented in the Monte-Carlo code McStas. Thirdly, achieving a complete study for the validation of the installed calculation chain. These studies focus on 3 cold sources currently functioning: SP1 from Orphee reactor and 2 other sources (SFH and SFV) from the HFR at the Laue Langevin Institute. These studies give examples of problems and methods for the design of future cold sources

  13. Selective serotonergic excitation of callosal projection neurons

    Directory of Open Access Journals (Sweden)

    Daniel eAvesar

    2012-03-01

    Full Text Available Serotonin (5-HT acting as a neurotransmitter in the cerebral cortex is critical for cognitive function, yet how 5-HT regulates information processing in cortical circuits is not well understood. We tested the serotonergic responsiveness of layer 5 pyramidal neurons (L5PNs of the mouse medial prefrontal cortex (mPFC, and found 3 distinct response types: long-lasting 5-HT1A (1A receptor-dependent inhibitory responses (84% of L5PNs, 5-HT2A (2A receptor-dependent excitatory responses (9%, and biphasic responses in which 2A-dependent excitation followed brief inhibition (5%. Relative to 5-HT-inhibited neurons, those excited by 5-HT had physiological properties characteristic of callosal/commissural (COM neurons that project to the contralateral cortex. We tested whether serotonergic responses in cortical pyramidal neurons are correlated with their axonal projection pattern using retrograde fluorescent labeling of COM and corticopontine-projecting (CPn neurons. 5-HT generated excitatory or biphasic responses in all 5-HT-responsive layer 5 COM neurons. Conversely, CPn neurons were universally inhibited by 5-HT. Serotonergic excitation of COM neurons was blocked by the 2A antagonist MDL 11939, while serotonergic inhibition of CPn neurons was blocked by the 1A antagonist WAY 100635, confirming a role for these two receptor subtypes in regulating pyramidal neuron activity. Selective serotonergic excitation of COM neurons was not layer-specific, as COM neurons in layer 2/3 were also selectively excited by 5-HT relative to their non-labeled pyramidal neuron neighbors. Because neocortical 2A receptors are implicated in the etiology and pathophysiology of schizophrenia, we propose that COM neurons may represent a novel cellular target for intervention in psychiatric disease.

  14. Cold forming of aluminium - State of the art

    DEFF Research Database (Denmark)

    Bay, Niels

    1997-01-01

    The ongoing development of cold forging technology has been manifested lately by the increasing application of components in cold forged aluminium alloys. Applying precipitation hardening alloys components with great strength/weight ratio can be produced with a strength comparable...... to that of unalloyed steel. After description of the different types of alloys and their individual properties and applications, the special requirements for tool design by cold forging in aluminium is discussed. Finally, a large number of industrial examples on cold forged aluminium components are presented. (C) 1997...

  15. De Novo Transcriptome Sequencing and the Hypothetical Cold Response Mode of Saussurea involucrata in Extreme Cold Environments.

    Science.gov (United States)

    Li, Jin; Liu, Hailiang; Xia, Wenwen; Mu, Jianqiang; Feng, Yujie; Liu, Ruina; Yan, Panyao; Wang, Aiying; Lin, Zhongping; Guo, Yong; Zhu, Jianbo; Chen, Xianfeng

    2017-06-07

    Saussurea involucrata grows in high mountain areas covered by snow throughout the year. The temperature of this habitat can change drastically in one day. To gain a better understanding of the cold response signaling pathways and molecular metabolic reactions involved in cold stress tolerance, genome-wide transcriptional analyses were performed using RNA-Seq technologies. A total of 199,758 transcripts were assembled, producing 138,540 unigenes with 46.8 Gb clean data. Overall, 184,416 (92.32%) transcripts were successfully annotated. The 365 transcription factors identified (292 unigenes) belonged to 49 transcription factor families associated with cold stress responses. A total of 343 transcripts on the signal transduction (132 upregulated and 212 downregulated in at least any one of the conditions) were strongly affected by cold temperature, such as the CBL-interacting serine/threonine-protein kinase ( CIPKs ), receptor-like protein kinases , and protein kinases . The circadian rhythm pathway was activated by cold adaptation, which was necessary to endure the severe temperature changes within a day. There were 346 differentially expressed genes (DEGs) related to transport, of which 138 were upregulated and 22 were downregulated in at least any one of the conditions. Under cold stress conditions, transcriptional regulation, molecular transport, and signal transduction were involved in the adaptation to low temperature in S. involucrata . These findings contribute to our understanding of the adaptation of plants to harsh environments and the survival traits of S. involucrata . In addition, the present study provides insight into the molecular mechanisms of chilling and freezing tolerance.

  16. Observation of stars produced during cold fusion

    International Nuclear Information System (INIS)

    Matsumoto, T.

    1992-01-01

    It has been indicated tht multiple-neutron nuclei such as quad-neutrons can be emitted during cold fusion. These multiple-neutrons might bombard the nuclei of materials outside a cold fusion cell to cause nuclear reactions. In this paper, observations of nuclear emulsions that were irradiated during a cold fusion experiment with heavy water and palladium foil are described. Various traces, like stars, showing nuclear reactions caused by the multiple-neutrons have been clearly observed

  17. Persistence of the cell-cycle checkpoint kinase Wee1 in SadA- and SadB-deficient neurons disrupts neuronal polarity.

    Science.gov (United States)

    Müller, Myriam; Lutter, Daniela; Püschel, Andreas W

    2010-01-15

    Wee1 is well characterized as a cell-cycle checkpoint kinase that regulates the entry into mitosis in dividing cells. Here we identify a novel function of Wee1 in postmitotic neurons during the establishment of distinct axonal and dendritic compartments, which is an essential step during neuronal development. Wee1 is expressed in unpolarized neurons but is downregulated after neurons have extended an axon. Suppression of Wee1 impairs the formation of minor neurites but does not interfere with axon formation. However, neuronal polarity is disrupted when neurons fail to downregulate Wee1. The kinases SadA and SadB (Sad kinases) phosphorylate Wee1 and are required to initiate its downregulation in polarized neurons. Wee1 expression persists in neurons that are deficient in SadA and SadB and disrupts neuronal polarity. Knockdown of Wee1 rescues the Sada(-/-);Sadb(-/-) mutant phenotype and restores normal polarity in these neurons. Our results demonstrate that the regulation of Wee1 by SadA and SadB kinases is essential for the differentiation of polarized neurons.

  18. Intratelencephalic corticostriatal neurons equally excite striatonigral and striatopallidal neurons and their discharge activity is selectively reduced in experimental parkinsonism

    OpenAIRE

    Ballion, B. (B.); Mallet, N. (Nicolas); Bezard, E. (E.); Lanciego, J.L. (José Luis); Gonon, F. (Francois)

    2008-01-01

    Striatonigral and striatopallidal neurons form distinct populations of striatal projection neurons. Their discharge activity is imbalanced after dopaminergic degeneration in Parkinson's disease. Striatal projection neurons receive massive cortical excitatory inputs from bilateral intratelencephalic (IT) neurons projecting to both the ipsilateral and contralateral striatum and from collateral axons of ipsilateral neurons that send their main axon through the pyramidal tract (PT). Previous anat...

  19. A novel behavioral assay for measuring cold sensation in mice.

    Directory of Open Access Journals (Sweden)

    Daniel S Brenner

    Full Text Available Behavioral models of cold responses are important tools for exploring the molecular mechanisms of cold sensation. To complement the currently cold behavioral assays and allow further studies of these mechanisms, we have developed a new technique to measure the cold response threshold, the cold plantar assay. In this assay, animals are acclimated on a glass plate and a cold stimulus is applied to the hindpaw through the glass using a pellet of compressed dry ice. The latency to withdrawal from the cooled glass is used as a measure of the cold response threshold of the rodents, and the dry ice pellet provides a ramping cold stimulus on the glass that allows the correlation of withdrawal latency values to rough estimates of the cold response threshold temperature. The assay is highly sensitive to manipulations including morphine-induced analgesia, Complete Freund's Adjuvant-induced inflammatory allodynia, and Spinal Nerve Ligation-induced neuropathic allodynia.

  20. Project COLD.

    Science.gov (United States)

    Kazanjian, Wendy C.

    1982-01-01

    Describes Project COLD (Climate, Ocean, Land, Discovery) a scientific study of the Polar Regions, a collection of 35 modules used within the framework of existing subjects: oceanography, biology, geology, meterology, geography, social science. Includes a partial list of topics and one activity (geodesic dome) from a module. (Author/SK)