An Ins(1,4,5)P3 receptor in Paramecium is associated with the osmoregulatory system

In the ciliate Paramecium, a variety of well characterized processes are regulated by Ca2+, e.g. exocytosis, endocytosis and ciliary beat. Therefore, among protozoa, Paramecium is considered a model organism for Ca2+ signaling, although the molecular identity of the channels responsible for the Ca2+ signals remains largely unknown. We have cloned - for the first time in a protozoan - the full sequence of the gene encoding a putative inositol (1,4,5)-trisphosphate (Ins(1,4,5)P3) receptor from Paramecium tetraurelia cells showing molecular characteristics of higher eukaryotic cells. The homologously expressed Ins(1,4,5)P3-binding domain binds [3H]Ins(1,4,5)P3, whereas antibodies unexpectedly localize this protein to the osmoregulatory system. The level of Ins(1,4,5)P3-receptor expression was reduced, as shown on a transcriptional level and by immuno-staining, by decreasing the concentration of extracellular Ca2+ (Paramecium cells rapidly adjust their Ca2+ level to that in the outside medium). Fluorochromes reveal spontaneous fluctuations in cytosolic Ca2+ levels along the osmoregulatory system and these signals change upon activation of caged Ins(1,4,5)P3. Considering the ongoing expulsion of substantial amounts of Ca2+ by the osmoregulatory system, we propose here that Ins(1,4,5)P3 receptors serve a new function, i.e. a latent, graded reflux of Ca2+ to fine-tune [Ca2+] homeostasis.

Quinols as novel therapeutic agents. 2.1 4-(1-arylsulfonylindol- 2-yl)-4-hydroxycyclohexa-2,5-dien-1-ones and related agents as potent and selective antitumor agents

A series of substituted 4-(1-arylsulfonylindol-2-yl)-4-hydroxycyclohexa-2, 5-dien-1-ones (indolylquinols) has been synthesized on the basis of the discovery of lead compound 1a and screened for antitumor activity. Synthesis of this novel series was accomplished via the "one-pot" addition of lithiated (arylsulfonyl)indoles to 4,4-dimethoxycyclohexa-2,5-dienone followed by deprotection under acidic conditions. Similar methodology gave rise to the related naphtho-, 1H-indole-, and benzimidazole-substituted quinols. A number of compounds in this new series were found to possess in vitro human tumor cell line activity substantially more potent than the recently reported antitumor 4-substituted 4-hydroxycyclohexa-2,5-dien-1-ones1 with similar patterns of selectivity against colon, renal, and breast cell lines. The most potent compound in the series in vitro, 4-(1-benzenesulfonyl-6-fluoro-1H-indol- 2-yl)-4-hydroxycyclohexa-2,5-dienone (1h), exhibits a mean GI50 value of 16 nM and a mean LC50 value of 2.24 μM in the NCI 60-cell-line screen, with LC50 activity in the HCT 116 human colon cancer cell line below 10 nM. The crystal structure of the unsubstituted indolylquinol 1a exhibits two independent molecules, both participating in intermolecular hydrogen bonds from quinol OH to carbonyl O, but one OH group also interacts intramolecularly with a sulfonyl O atom. This interaction, which strengthens upon ab initio optimization, may influence the chemical environment of the bioactive quinol moiety. In vivo, significant antitumor activity was recorded (day 28) in mice bearing subcutaneously implanted MDA-MB-435 xenografts, following intraperitoneal treatment of mice with compound 1a at 50 mg/kg.

Synthesis of substituted 3-anilino-5-phenyl-1,3-dihydro-2H-1,4-benzodiazepine-2-ones and their evaluation as cholecystokinin-ligands

3-Amino-1,4-benzodiazepines as well as chemically related diverse amines were prepared from oxazepam and subsequently screened on the cholecystokinin receptor in a radiolabel binding assay. Oxazepam 2 was activated via its 3-chloro-1,4-benzodiazepine intermediate 3 and was reacted with a large series of aliphatic and aromatic amines. The substituted 3-anilino-1,4-benzodiazepine structure was identified as lead structure in a diverse series of 3-amino-1,4-benzodiazepines 4-38 and the full SAR (structure-activity relationship) optimisation provided 3-anilinobenzodiazepines 16-38 with CCK 1 receptor selectivity to CCK 2. The compounds 18, 24, 28 and 33 have shown affinities at the CCK 1 receptor of 11, 10, 11 and 9 nM, respectively. These equipotent CCK 1 ligands were fully evaluated in behaviour pharmacological essays. An antidepressant effect was identified in the tail suspension- and the Porsolt swimming-test. The ED 50 values for 24 and 28 were determined in these assays as 0.46 and 0.49 mg/kg. The mixed antagonist 37 showed in addition to the antidepressant effects anxiolytic properties. © 2006 Wiley-VCH Verlag GmbH & Co. KGaA.

On the Hyperbolicity Domain of the Polynomial x^n + a1x^(n-1) + 1/4+ an

∗ Partially supported by INTAS grant 97-1644

Efficient 1,4-addition of enones and boronic acids catalyzed by a Ni-Zn hydroxyl double salt-intercalated anionic rhodium(III) complex

Intercalation of an in situ prepared [Rh(OH)6]3- complex into an anion exchangeable Ni-Zn layered hydroxy double salt (Rh/NiZn) was demonstrated. The resulting Rh/NiZn effectively catalyzed the 1,4-addition of diverse enones and phenylboronic acids to their corresponding β-substituted carbonyl compounds. In the case of 2-cyclohexen-1-one and phenylboronic acid, a turnover frequency (TOF) of 920 h-1 based on Rh was achieved. The [Rh(OH)6]3- complex maintained its original monomeric trivalent state within the NiZn interlayer following catalysis, attributable to a strong electrostatic interaction between the NiZn host and anionic Rh(III) complex.

Antidepressant/anxiolytic and anti-nociceptive effects of novel 2-substituted 1,4-benzodiazepine-2-ones

Oxazepam (4a) has been used as overall starting material in the synthesis of novel 2-substituted 1,4-benzodiazepines. By reacting Oxazepam 4a with commercially available hydrazines, hydrazides, semicarbazide, aminoguanidine and N,N-dimethylamino aniline in ethanol under acetic conditions, a series of diazenyl-1,4-benzodiazepines 5a-5i and 2-amino- 1,4-benzodiazepine 5k were obtained in good yields. These novel compounds served as new chemical entities (NCE) for testing in mice. The diazo-benzodiazepine 5d has shown a promising antidepressant effect in initial experiments in vivo at a dose of 5 mg/kg. The highly coloured 2-aminobenzodiazepine derivative 5k showed over a dose range from 5-50 mg/kg an analgesic effect in mice. © Singh et al.

MID-IR luminosities and UV/optical star formation rates at z < 1.4

Ultraviolet (UV) nonionizing continuum and mid-infrared (IR) emission constitute the basis of two widely used star formation (SF) indicators at intermediate and high redshifts. We study 2430 galaxies with z < 1.4 in the Extended Groth Strip with deep MIPS 24 μm observations from FIDEL, spectroscopy from DEEP2, and UV, optical, and near-IR photometry from the AEGIS. The data are coupled with dust-reddened stellar population models and Bayesian spectral energy distribution (SED) fitting to estimate dust-corrected star formation rates (SFRs). In order to probe the dust heating from stellar populations of various ages, the derived SFRs were averaged over various timescales—from 100 Myr for "current" SFR (corresponding to young stars) to 1-3 Gyr for long-timescale SFRs (corresponding to the light-weighted age of the dominant stellar populations). These SED-based UV/optical SFRs are compared to total IR luminosities extrapolated from 24 μm observations, corresponding to 10-18 μm rest frame. The total IR luminosities are in the range of normal star-forming galaxies and luminous IR galaxies (10^10-10^12 L_☉). We show that the IR luminosity can be estimated from the UV and optical photometry to within a factor of 2, implying that most z < 1.4 galaxies are not optically thick. We find that for the blue, actively star-forming galaxies the correlation between the IR luminosity and the UV/optical SFR shows a decrease in scatter when going from shorter to longer SFR-averaging timescales. We interpret this as the greater role of intermediate age stellar populations in heating the dust than what is typically assumed. Equivalently, we observe that the IR luminosity is better correlated with dust-corrected optical luminosity than with dust-corrected UV light. We find that this holds over the entire redshift range. Many so-called green valley galaxies are simply dust-obscured actively star-forming galaxies. However, there exist 24 μm detected galaxies, some with L_IR>10^11 L_☉, yet with little current SF. For them a reasonable amount of dust absorption of stellar light (but presumably higher than in nearby early-type galaxies) is sufficient to produce the observed levels of IR, which includes a large contribution from intermediate and old stellar populations. In our sample, which contains very few ultraluminous IR galaxies, optical and X-ray active galactic nuclei do not contribute on average more than ~50% to the mid-IR luminosity, and we see no evidence for a large population of "IR excess" galaxies.

The host galaxies and black holes of typical z~0.5-1.4 AGNs

We study the stellar and star formation properties of the host galaxies of 58 X-ray-selected AGNs in the GOODS portion of the Chandra Deep Field South (CDF-S) region at z ~ 0.5-1.4. The AGNs are selected such that their rest-frame UV to near-infrared spectral energy distributions (SEDs) are dominated by stellar emission; i.e., they show a prominent 1.6 μm bump, thus minimizing the AGN emission "contamination." This AGN population comprises approximately 50% of the X-ray-selected AGNs at these redshifts. We find that AGNs reside in the most massive galaxies at the redshifts probed here. Their characteristic stellar masses (M_* ~ 7.8 × 10^10 and M_* ~ 1.2 × 10^11 M_☉ at median redshifts of 0.67 and 1.07, respectively) appear to be representative of the X-ray-selected AGN population at these redshifts and are intermediate between those of local type 2 AGNs and high-redshift (z ~ 2) AGNs. The inferred black hole masses (M_BH ~ 2 × 10^8 M_☉) of typical AGNs are similar to those of optically identified quasars at similar redshifts. Since the AGNs in our sample are much less luminous (L_2–10 keV < 10^44 erg s^−1) than quasars, typical AGNs have low Eddington ratios (η ~ 0.01-0.001). This suggests that, at least at intermediate redshifts, the cosmic AGN "downsizing" is due to both a decrease in the characteristic stellar mass of typical host galaxies and less efficient accretion. Finally, there is no strong evidence in AGN host galaxies for either highly suppressed star formation (expected if AGNs played a role in quenching star formation) or elevated star formation when compared to mass-selected (i.e., IRAC-selected) galaxies of similar stellar masses and redshifts.

Understanding the twist-bend nematic phase: the characterisation of 1-(4-cyanobiphenyl-4'-yloxy)-6-(4-cyanobiphenyl-4'-yl) hexane (CB6OCB) and comparison with CB7CB

Acknowledgements The FFTEM data were obtained at the (Cryo) TEM facility at the Liquid Crystal Institute, Kent State University, supported by the Ohio Research Scholars Program Research Cluster on Surfaces in Advanced Materials. ODL acknowledges the support of NSF DMR-1410378 grant. The authors are grateful for financial support from MINECO/FEDER MAT2015-66208-C3-2-P and from the Gobierno Vasco (GI/IT-449-10)

A critical review of both the synthesis approach and the receptor profile of the 8-chloro-1-(2′,4′-dichlorophenyl)-N-piperidin-1-yl-1,4,5,6-tetrahydrobenzo[6,7]cyclohepta[1,2-c]pyrazole-3-carboxamide and analogue derivatives

We thank European Commission (project “PET BRAIN: Mapping the brain with PET radiolabeled cannabinoid CB1 ligands”; FP7-People-2009-IAPP; Grant Agreement N.25142).

Evaluation of strontium-site-deficient Sr2Fe1.4Co0.1Mo0.5O6-δ-based perovskite oxides as intermediate temperature solid oxide fuel cell cathodes

In this paper strontium-site-deficient Sr₂Fe_1.4Co_0.1Mo_0.5O_6-δ-based perovskite oxides (S_xFCM) were prepared and evaluated as the cathode materials for intermediate temperature solid oxide fuel cells (IT-SOFCs). All samples exhibited a cubic phase structure and the lattice shrinked with increasing the Sr-deficiency as shown in XRD patterns. XPS results determined that the transition elements (Co/Fe/Mo) in S_xFCM oxides were in a mixed valence state, demonstrating the small polaron hopping conductivity mechanism existed. Among the samples, S_1.950FCM presented the lowest coefficient of thermal expansion of 15.62 × 10^-6 K^-1, the highest conductivity value of 28 S cm^-1 at 500 °C, and the lowest interfacial polarization resistance of 0.093 Ω cm² at 800 °C, respectively. Furthermore, an anode-supported single cell with a S_1.950FCM cathode was prepared, demonstrating a maximum power density of 1.16 W cm^-2 at 800 °C by using wet H₂ (3% H₂O) as the fuel and ambient air as the oxidant. These results indicate that the introduction of Sr-deficiency can dramatically improve the electrochemical performance of Sr₂Fe_1.4Co_0.1Mo_0.5O_6-δ, showing great promise as a novel cathode candidate material for IT-SOFCs.

High performance cobalt-free Cu1.4Mn1.6O4 spinel oxide as an intermediate temperature solid oxide fuel cell cathode

In this work Cu_1.4Mn_1.6O₄ (CMO) spinel oxide is prepared and evaluated as a novel cobalt-free cathode for intermediate temperature solid oxide fuel cells (IT-SOFCs). Single phase CMO powder with cubic structure is identified using XRD. XPS results confirm that mixed Cu⁺/Cu²⁺ and Mn³⁺/Mn⁴⁺ couples exist in the CMO sample, and a maximum conductivity of 78 S cm⁻¹ is achieved at 800 °C. Meanwhile, CMO oxide shows good thermal and chemical compatibility with a 10 mol% Sc₂O₃ stabilized ZrO₂ (ScSZ) electrolyte material. Impedance spectroscopy measurements reveals that CMO exhibits a low polarization resistance of 0.143 Ω cm² at 800 °C. Furthermore, a Ni-ScSZ/ScSZ/CMO single cell demonstrates a maximum power density of 1076 mW cm⁻² at 800 °C under H₂ (3% H₂O) as the fuel and ambient air as the oxidant. These results indicate that Cu_1.4Mn_1.6O₄ is a superior and promising cathode material for IT-SOFCs.