290 research outputs found
PIP2 Modulation of Afterhyperpolarizations in Magnocellular Supraoptic Neurons
Magnocellular neurosecretory cells (MNCs) are large oxytocin (OT)- and vasopressin (VP)-releasing neurons that secrete these hormones into the circulatory system in response to physiological stimuli. These cells exhibit unique phasic and burst firing patterns to release these peptides into the circulatory system where they primarily control milk ejection and parturition (OT) as well as salt-water balance and vasoconstriction (VP). This firing is underlain by intrinsic ionic mechanisms that shape the duration and frequency of these bursts. One of these mechanisms is the Ca2+-dependent afterhyperpolarization (AHP), which activates during bursts and causes spike frequency adaptation. This afterhyperpolarization has three distinct conductances: a fast component (fAHP) underlain by BK channels, a medium component (mAHP) underlain by apamin-sensitive SK channels, and a slow component (sAHP) which is an apamin-insensitive K+ conductance. The mechanisms that control the sAHP are poorly understood in MNCs. The work embodied here explores the mechanisms involved in generation of AHPs, specifically how the phospholipid, PIP2 can activate and modulate the mAHP and sAHP. The major discovery is that the mechanisms that generate mAHP and sAHP are different between OT and VP neurons. PIP2 depletion via wortmannin in the cells abolishes the mAHP and sAHP of OT but not VP neurons. This demonstrates OT neurons require PIP2 to activate an AHP while VP neurons do not. Interestingly, increasing PIP2 within the cells has little effect on OT neurons while drastically enhancing the sAHP in VP neurons, thus PIP2 plays a different role in both cell types. In OT neurons, PIP2 exerts its effect by facilitating Ca2+ entry through voltage-gated Ca2+ channels, demonstrated by inhibited Ca2+ currents in the presence of wortmannin.
The mechanistic differences extend to which Ca2+ channels contribute Ca2+ to the mAHP and sAHP. In OT neurons, N-type Ca2+ channels couple primarily to both components. In VP neurons, N-type channels couple to the mAHP while the sAHP receives a contribution from R-type channels. The precise way PIP2 modulates Ca2+ channels in OT neurons is explored further in dissociated neurons genetically labeled for OT or VP. PIP2 depletion inhibited the amplitude, shifted the steady-state activation curve leftward, and modestly accelerated the inactivation of both the whole-cell and isolated N-type current in OT neurons only. This suggests that PIP2 is not required, but is a co-factor, for channel activation. The PIP2 mechanisms of AHP modulation in VP neurons appear complex, as the enhancement observed during increased PIP2 didn’t occur when EGTA was replaced with fura-2 in the pipette. In order to understand what happens to [Ca2+]i during this enhancement, we changed the Ca2+ indicator to fluo-4 and was able to observe enhancement under specific conditions. This suggests that VP modulation is critically dependent on the time course and buffering of available Ca2+.
Finally, I also performed a cursory evaluation of possible morphological implications in AHP generation. I used regression analysis to assess the relationships between AHP amplitude, [Ca2+]i, and dendritic size. There is a moderate relationship between AHP amplitude and dendritic length in both OT and VP neurons, suggesting that a considerable portion of the AHP conductance could occur in the dendritic tree of these neurons. These studies highlight the unique AHP mechanisms between OT and VP neurons of supraoptic nucleus
(η5-Cyclopentadienyl)(propionitrile-κN)bis(triphenylphosphine-κP)ruthenium(II) trifluoromethanesulfonate
The title compound, [Ru(C5H5)(C3H5N)(C18H15P)2]CF3SO3, forms yellow crystals with a distinctly hemimorphic habit. It contains a half-sandwich complex of ruthenium with a three-legged piano-stool geometry, with Ru—P = 2.3585 (4) and 2.3312 (4) Å, and Ru—N = 2.0422 (15) Å as the legs. The CF3SO3
− anion is anchored in the crystal lattice by C—H⋯O and C—H⋯F hydrogen bonds, with C⋯F,O distances starting at 3.125 (2) Å
Quantifizierbarkeit von Risiken auf Finanzmärkten
Die Krise der internationalen Finanzmärkte hat die allgemeine Wahrnehmung für die in diesen Märkten inhärenten Risiken merklich verändert. Glaubten manche Anleger in den Boomphasen der Finanzmärkte, dass sich eine hohe Kapitalrendite mit geringem Risiko verbinden ließe, wenn man nur die Finanzprodukte entsprechend gestaltete, hat sich diese Wahnvorstellung zwischenzeitlich verflüchtigt. Will man vernünftig mit diesen Risiken umgehen, ist es notwendig, diese quantifizieren zu können. Hier gilt es, eine Reihe methodischer Probleme zu bewältigen, da sich einfache statistische Methodiken als nicht adäquat für die vielschichtigen Finanzmarktrisiken erweisen. Die Vielschichtigkeit dieser Risiken hat in den letzten Jahrzehnten zugenommen, insbesondere seitdem hypothekengesicherte Darlehen in verbriefter und verpackter Form auf Finanzmärkten abgesetzt wurden. Der Fokus der folgenden Ausführungen liegt bei der Quantifizierung der Risikoeinschätzungen, und zwar unter Beachtung von Wahrnehmungsproblemen, wie sie in der modernen Verhaltensökonomik erörtert werden. Daneben werden aber auch Probleme des demographischen Risikos angesprochen.pricing kernels, risk aversion, risk neutral density
Chlorido(chlorodiphenylphosphine-κP)(diphenylpiperidinophosphine-κP)(η5-pentamethylcyclopentadienyl)ruthenium(II)
The title compound, [Ru(C10H15)Cl(C12H10ClP)(C17H20NP)], is a half-sandwich complex of RuII with the chlorodiphenylphosphine ligand formed from the diphenylpiperidinophosphine and chlorine of the precursor complex [Ru(η5-C5Me5)(κ1P—Ph2PNC5H10)Cl2] by an unexpected reaction with NaBH4. The complex has a three-legged piano-stool geometry, with Ru—P bond lengths of 2.2598 (5) Å for the chlorophosphine and 2.3303 (5) Å for the aminophosphine
(η5-Cyclopentadienyl)(η6-mesitylamine)ruthenium(II) hexafluoridophosphate
The title compound, [Ru(η5-C5H5){η6-C6H2(CH3)3NH2}]PF6, contains a sandwich complex with a mesitylamine unit which is significantly non-planar at the ipso-carbon of the amino group due to repulsive electronic effects with Ru. The ipso-carbon deviates by 0.107 (3) Å from the least-squares plane of the remaining five benzene ring atoms, which show an r.m.s. deviation of 0.005 Å. N—H⋯F hydrogen-bonding interactions help to consolidate the crystal packing
АНАЛИЗ ПОГРЕШНОСТЕЙ ЦИФРОАНАЛОГОВЫХ ПРЕОБРАЗОВАТЕЛЕЙ
В данной статье анализируются погрешности
цифроаналоговых преобразователей. Для этого
рассмотрены различные источники погрешностей
и способы их устранения
Hepatic progenitor cells from adult human livers for cell transplantation.
Objective: Liver regeneration is mainly based on cellular
self-renewal including progenitor cells. Efforts have been
made to harness this potential for cell transplantation, but
shortage of hepatocytes and premature differentiated
progenitor cells from extra-hepatic organs are limiting
factors. Histological studies implied that resident cells in
adult liver can proliferate, have bipotential character and
may be a suitable source for cell transplantation.
Methods: Particular cell populations were isolated after
adequate tissue dissociation. Single cell suspensions were
purified by Thy-1 positivity selection, characterised in vitro
and transplanted in immunodeficient Pfp/Rag2 mice.
Results: Thy-1+ cells that are mainly found in the portal
tract and the surrounding parenchyma, were isolated from
surgical liver tissue with high yields from specimens with
histological signs of regeneration. Thy-1+ cell populations
were positive for progenitor (CD34, c-kit, CK14, M2PK,
OV6), biliary (CK19) and hepatic (HepPar1) markers
revealing their progenitor as well as hepatic and biliary
nature. The potential of Thy-1+ cells for differentiation in
vitro was demonstrated by increased mRNA and protein
expression for hepatic (CK18, HepPar1) and biliary (CK7)
markers during culture while progenitor markers CK14,
chromogranin A and nestin were reduced. After
transplantation of Thy-1+ cells into livers of immunodeficient
mice, engraftment was predominantly seen in the
periportal portion of the liver lobule. Analysis of in situ
material revealed that transplanted cells express human
hepatic markers HepPar1 and albumin, indicating functional
engraftment.
Conclusion: Bipotential progenitor cells from human
adult livers can be isolated using Thy-1 and might be a
potential candidate for cell treatment in liver diseases
Tris(acetonitrile-κN){2,6-bis[(diphenylphosphanyl)amino]-4-ethoxy-1,3,5-triazine-κ3 P,N 1,P′}iron(II) bis(tetrafluoridoborate) acetonitrile disolvate
In the title compound, [Fe(CH3CN)3(C29H27N5OP2)](BF4)2·2CH3CN, the FeII ion is octahedrally coordinated by a meridionally chelating tridentate pincer-type PNP ligand derived from 2,6-diamino-4-ethoxy-1,3,5-triazine and by three acetonitrile molecules. The four Fe—N bond lengths range from 1.9142 (12) to 1.9579 (11) Å, while the Fe—P bonds are 2.2452 (4) and 2.2506 (4) Å [P—Fe—P = 165.523 (14)°], consistent with FeII in a low-spin state. Unlike related Fe PNP complexes based on 2,6-diaminopyridine, the BF4 anions are not hydrogen bonded to the two NH groups of the pincer ligand but show instead anion–π interactions with the triazine ring and acetonitrile molecules in addition to ten C—H⋯F interactions. Most remarkable among these is an anion–π(triazine) interaction with a short distance of 2.788 (2) Å between one F and the centroid of the π-acidic triazine ring. The corresponding shortest distance between this F atom and a triazine carbon atom is 2.750 (2) Å. The two NH groups of the pincer ligand donate N—H⋯N hydrogen bonds to the triazine N atom of a neighbouring complex and to an uncoordinated acetonitrile molecule. This last molecule is in a side-on head-to-tail association with the second uncoordinated acetonitrile at C⋯N distances of 3.467 (2) and 3.569 (2) Å. In contrast to several related compounds with diaminopyridine- instead of diaminotriazine-based PNP ligands, the title crystal structure is remarkably well ordered. This suggests that the diaminotriazine moiety exerts notable crystal structure stabilizing effects
- …