Estrogen induces estrogen receptor alpha-dependent cAMP response element-binding protein phosphorylation via mitogen activated protein kinase pathway in basal forebrain cholinergic neurons in vivo

In addition to classical genomic mechanisms, estrogen also exerts nonclassical effects via a signal transduction system on neurons. To study whether estrogen has a nonclassical effect on basal forebrain cholinergic system, we measured the intensity of cAMP response element-binding protein (CREB) phosphorylation (pCREB) in cholinergic neurons after administration of 17 beta-estradiol to ovariectomized (OVX) mice. A significant time-dependent increase in the number of pCREB-positive cholinergic cells was detected after estrogen administration in the medial septum-diagonal band (MS-DB) and the substantia innominata ( SI). The increase was first observed 15 min after estrogen administration. The role of classical estrogen receptors (ERs) was evaluated using ER knock-out mice in vivo. The estrogen-induced CREB phosphorylation in cholinergic neurons was present in ER beta knock-out mice but completely absent in ER beta knock-out mice in MS-DB and SI. A series of in vitro studies demonstrated that estrogen acted directly on cholinergic neurons. Selective blockade of the mitogen activated protein kinase (MAPK) pathway in vivo completely prevented estrogen-induced CREB phosphorylation in cholinergic neurons in MS-DB and SI. In contrast, blockade of protein kinase A (PKA) was effective only in SI. Finally, studies in intact female mice revealed levels of CREB phosphorylation within cholinergic neurons that were similar to those of estrogen-treated OVX mice. These observations demonstrate an ER alpha-mediated nonclassical effect of estrogen on the cholinergic neurons and that these actions are present under physiological conditions. They also reveal the role of MAPK and PKA-MAPK pathway activation in nonclassical estrogen signaling in the basal forebrain cholinergic neurons in vivo

Covariance and Fisher information in quantum mechanics

Variance and Fisher information are ingredients of the Cramer-Rao inequality. We regard Fisher information as a Riemannian metric on a quantum statistical manifold and choose monotonicity under coarse graining as the fundamental property of variance and Fisher information. In this approach we show that there is a kind of dual one-to-one correspondence between the candidates of the two concepts. We emphasis that Fisher informations are obtained from relative entropies as contrast functions on the state space and argue that the scalar curvature might be interpreted as an uncertainty density on a statistical manifold.Comment: LATE

Fenntartható fluoros kémia = Sustainable fluorous chemistry

(1) A „zöldebb” fluoros kémia kialakítása érdekében számos trifluormetil-csoportban gazdag reagens hatékony szintézisét dolgoztuk ki, melyek könnyen hozzáférhető szerves fluorvegyületek hasznosítására és várhatóan nagyobb környezeti lebomlási készségére hívják fel a figyelmet. (2) Eljárásokat dolgoztunk ki 3-perfluoralkil-propanol és 3-perfluoralkil-propén típusú intermedierek előállítására, illetve a köztitermékként megjelenő ún. jódhidrinek sokoldalú preparatív átalakítására. (3) Új típusú fluoros ionos folyadékokat, imidazólium-sókat és más intermediereket állítottunk elő. (4) Orosz fejlesztésű kompozit anyagokat (FUKM, FUKM-M és FUKM-MT) kémiai reagensként, illetve átmenetifém katalizátor (Pd/FUKM) hordozóként alkalmaztunk. (5) Tanulmányoztuk a Hiyama- és a Heck-kapcsolási reakciók mechanizmusát és szintetikus alkalmazhatóságát. (6) CF3I reagnest S-alkilezőszerként alkalmaztuk (7) Prof. Bühlmann al együttműködve fluoros ionofórokat és elektrokémiai szenzorokat készítettünk. (8) Azonosítottuk egy új potenciális fluorátvivő reagens molekulaszerkezeti feltételeit, melynek segítségével lehetőségünk nyílik a fluoros kémiából (fluortartalmú modulok) a fluorkémiába (szén-fluor kötesek kialakítása) átlépnünk. Ez lehetőséget ad a gyógyszerkémia számára fontos egy, kettő, vagy három fluoratomot tartalmazó vegyületek hatékony előállításához. Több közlemény csak a kövtekező évben fog megjelenni, kérem az értékelésnél ezt vegyék figyelembe. | (1) For Greener Fluorous Chemistry we developed the synthesis of several reagents from easily accessible precursor, reach in CF3-goups, which expected to have less impact and shorter environmental half-lives. (2) Novel methods for the synthesis of 3-perfluoroalkyl-propanols and –propenes were disclosed along with the uses of their synthetic intermediates. (3) New types of fluorous ionic liquids were synthesised based on imidazolium-salts. (4) Carbon-fluorinated carbon composite materials of Russian origin were applied as chemical reagents and transition metal catalyst support material (e.g. Pd/FUKM) . (5) Hiyama- and Heck-reactions with fluorous substrates were studied for a synthetic and mechanistic point of view. (6) Trifluoroiodomethane was used for improved S-alkylating processes. (7) Fluorous ionophores and electrochemical sensors were designed for the first time in co-operation with Prof. Bühlmann. (8) The structural requirements for a potential new fluorine-transfer reagent were identified and a Patentable process designed. This will allow the introduction of one, two or three fluorine atoms into target pharmaceutical molecules, and allow a shift from the fluorous to the fluorine chemistry (i.e. from F-building blocks to create C-F bonds). Please consider that some more publications are expected to appear only in the next year

Recommended ideal-gas thermochemical functions for heavy water and its Substituent isotopologues

Accurate temperature-dependent ideal-gas internal partition functions, Qint(T), and several derived thermochemical functions are reported for heavy water, with an oxygen content corresponding to the isotopic composition of Vienna Standard Mean Ocean Water (VSMOW), and its constituent isotopologues, D216O, D217O, and D218O, for temperatures between 0 and 6000 K. The nuclear-spin-dependent partition functions are obtained by the direct summation technique, involving altogether about 16 000 measured and more than nine million computed bound rovibrational energy levels for the three molecules. Reliable standard uncertainties, as a function of temperature, are estimated for each thermochemical quantity determined, including the enthalpy, the entropy, and the isobaric heat capacity of the individual nuclear-spin-equilibrated isotopologues and of heavy water. The accuracy of the heavy-water ideal-gas Cp(T) is unprecedented, below 0.01% up to 1800 K. All the thermochemical functions are reported, in 1 K increments, in the supplementary material

Cold gas outflows from the Small Magellanic Cloud traced with ASKAP

Feedback from massive stars plays a critical role in the evolution of the Universe by driving powerful outflows from galaxies that enrich the intergalactic medium and regulate star formation. An important source of outflows may be the most numerous galaxies in the Universe: dwarf galaxies. With small gravitational potential wells, these galaxies easily lose their star-forming material in the presence of intense stellar feedback. Here, we show that the nearby dwarf galaxy, the Small Magellanic Cloud (SMC), has atomic hydrogen outflows extending at least 2 kiloparsecs (kpc) from the star-forming bar of the galaxy. The outflows are cold, $T<400~{\rm K}$, and may have formed during a period of active star formation $25 - 60$ million years (Myr) ago. The total mass of atomic gas in the outflow is $\sim 10^7$ solar masses, ${\rm M_{\odot}}$, or $\sim 3$% of the total atomic gas of the galaxy. The inferred mass flux in atomic gas alone, $\dot{M}_{HI}\sim 0.2 - 1.0~{\rm M_{\odot}~yr^{-1}}$, is up to an order of magnitude greater than the star formation rate. We suggest that most of the observed outflow will be stripped from the SMC through its interaction with its companion, the Large Magellanic Cloud (LMC), and the Milky Way, feeding the Magellanic Stream of hydrogen encircling the Milky Way.Comment: Published in Nature Astronomy, 29 October 2018, http://dx.doi.org/10.1038/s41550-018-0608-

Transfer of complex regional pain syndrome to mice via human autoantibodies is mediated by interleukin-1–induced mechanisms

Neuroimmune interactions may contribute to severe pain and regional inflammatory and autonomic signs in complex regional pain syndrome (CRPS), a posttraumatic pain disorder. Here, we investigated peripheral and central immune mechanisms in a translational passive transfer trauma mouse model of CRPS. Small plantar skin–muscle incision was performed in female C57BL/6 mice treated daily with purified serum immunoglobulin G (IgG) from patients with longstanding CRPS or healthy volunteers followed by assessment of paw edema, hyperalgesia, inflammation, and central glial activation. CRPS IgG significantly increased and prolonged swelling and induced stable hyperalgesia of the incised paw compared with IgG from healthy controls. After a short-lasting paw inflammatory response in all groups, CRPS IgG-injected mice displayed sustained, profound microglia and astrocyte activation in the dorsal horn of the spinal cord and pain-related brain regions, indicating central sensitization. Genetic deletion of interleukin-1 (IL-1) using IL-1αβ knockout (KO) mice and perioperative IL-1 receptor type 1 (IL-1R1) blockade with the drug anakinra, but not treatment with the glucocorticoid prednisolone, prevented these changes. Anakinra treatment also reversed the established sensitization phenotype when initiated 8 days after incision. Furthermore, with the generation of an IL-1β floxed(fl/fl) mouse line, we demonstrated that CRPS IgG-induced changes are in part mediated by microglia-derived IL-1β, suggesting that both peripheral and central inflammatory mechanisms contribute to the transferred disease phenotype. These results indicate that persistent CRPS is often contributed to by autoantibodies and highlight a potential therapeutic use for clinically licensed antagonists, such as anakinra, to prevent or treat CRPS via blocking IL-1 actions

The ALICE detector data link

The ALICE detector data link has been designed to cover all the needs for data transfer between the detector and the data-acquisition system. It is a 1 Gbit/s, full-duplex, multi-purpose fibre optic link that can be used as a medium for the bi-directional transmission of data blocks between the front-end electronics and the data- acquisition system and also for the remote control and test of the front-end electronics, In this paper the concept, the protocol, the specific test tools, the prototypes of the detector data link and the read-out receiver card, their application in the ALICE-TPC test system and the integration with the DATE software are presented. The test results on the performance are also shown. (14 refs)