A novel, two-step synthesis of 4-pyridone-3-carboxamides from 2-cyano-4-pyrones

Reactions of 2-cyano-6-(trifluoromethyl)-4-pyrone, 2-cyano-4-pyrone, and 2-cyano-6-methyl-4-pyrone with aliphatic and aromatic amines in ethanol at -20 C for 2-21 days gave 5-amino-3-oxopent-4-enamides in 28-78% yields, which were cyclized with DMF-DMA in toluene under ambient conditions to afford 4-pyridone-3-carboxamides in 31-70% yields. © 2013 Elsevier Ltd. All rights reserved

Cerebellar anaplastic astrocytoma in adult patients: 15 consecutive cases from a single institution and literature review

Adult cerebellar anaplastic astrocytomas (cAA) are rare entities and their clinical and genetic appearances are still ill defined. Previously, malignant gliomas of the cerebellum were combined and reviewed together (cAA and cerebellar glioblastomas (cGB), that could have possibly affected overall survival (OS) and progression-free survival (PFS). We present characteristics of 15 adult patients with cAA and compared them to a series of 45 patients with a supratentorial AA (sAA) in order to elicit the effect of tumor location on OS and PFS. The mean age at cAA diagnosis was 39.3 years (range 19–72). A history of neurofibromatosis type I was noted in 1 patient (6.7%). An IDH-1 mutation was identified in 6/15 cases and a methylated MGMT promoter in 5/15 cases. Patients in study and control groups were matched in age, sex and IDH-1 mutation status. Patients in a study group tended to present with longer overall survival (50 vs. 36.5 months), but the difference did not reach statistical significance. In both cAA and supratentorial AA groups presence of the IDH-1 mutation remains a positive predictor for the prolonged survival. The present study suggests that adult cAA constitute a group of gliomas with relatively higher rate of IDH-1 mutations and prognosis similar to supratentorial AA. The present study is the first to systematically compare cAA and supratentorial AA with respect to their genetic characteristics and suggests that both groups show a similar survival prognosis

The C-type natriuretic peptide induces thermal hyperalgesia through a noncanonical Gβγ-dependent modulation of TRPV1 channel

Natriuretic peptides (NPs) control natriuresis and normalize changes in blood pressure. Recent studies suggest that NPs are also involved in the regulation of pain sensitivity, although the underlying mechanisms remain largely unknown. Many biological effects of NPs are mediated by guanylate cyclase (GC)-coupled NP receptors, NPR-A and NPR-B, whereas the third NP receptor, NPR-C, lacks the GC kinase domain and acts as the NP clearance receptor. In addition, NPR-C can couple to specific Gα(i)-βγ-mediated intracellular signaling cascades in numerous cell types. We found that NPR-C is co-expressed in TRPV1-expressing mouse DRG neurons. NPR-C can be co-immunoprecipitated with Gα(i), and CNP treatment induced translocation of PKCε to the plasma membrane of these neurons, which was inhibited by pertussis toxin pre-treatment. Application of CNP potentiated capsaicin- and proton-activated TRPV1 currents in cultured mouse DRG neurons, and increased neuronal firing frequency, an effect that was absent in DRG neurons from TRPV1(−/−) mice. CNP-induced sensitization of TRPV1 activity was attenuated by pre-treatment of DRG neurons with the specific inhibitors of Gβγ, PLCβ or PKC, but not of PKA, and was abolished by mutations at two PKC phosphorylation sites in TRPV1. Further, CNP injection into mouse hind paw led to the development of thermal hyperalgesia that was attenuated by administration of specific inhibitors of Gβγ or TRPV1, and was also absent in TRPV1(−/−) mice. Thus, our work identifies the Gβγ-PLCβ-PKC-dependent potentiation of TRPV1 as a novel signaling cascade recruited by CNP in mouse DRG neurons that can lead to enhanced nociceptor excitability and thermal hypersensitivity

NMR Studies of the Mn²⁺ Interactions with Amyloid Peptide Aβ13-23 in Water Environment

© 2016, Springer Science+Business Media New York.In this paper, binding of Mn2+ ions to the fragment of beta-amyloid peptide (Aβ13-23) was studied. Manganese complexation induces important structural changes within the C-terminal segment of the peptide. Investigation of peptide–metal ion binding was made by MnCl2 salt titration and recording 2D 1H–1H NMR TOCSY spectra (TOtal Correlation SpectroscopY). Multidimensional NMR techniques were performed to understand the details of the conformational behavior of the peptide and to reveal the metal-binding sites. According to changes in NMR spectra, the manganese-binding center of the Aβ13-23 peptide is associated with the aspartate residue

Particle flows in a dc discharge in laboratory and microgravity conditions

We describe a series of experiments on dust particles flows in a positive column of a horizontal dc discharge operating in laboratory and microgravity conditions. The main observation is that the particle flow velocities in laboratory experiments are systematically higher than in microgravity experiments, for otherwise identical discharge conditions. The paper provides an explanation for this interesting and unexpected observation. The explanation is based on a physical model, which properly takes into account main plasma-particle interaction mechanisms relevant to the described experimental study. Comparison of experimentally measured particle velocities and those calculated using the proposed model demonstrates reasonable agreement, both in laboratory and microgravity conditions, in the entire range of discharge parameters investigated.Comment: 9 pages, 7 figure

2-aryl-6-Polyfluoroalkyl-4-Pyrones as Promising Rf-Building-Blocks: Synthesis and Application for Construction of Fluorinated Azaheterocycles

A convenient and general method for the direct synthesis of 2-aryl-6-(trifluoromethyl)-4-pyrones and 2-aryl-5-bromo-6-(trifluoromethyl)-4-pyrones has been developed on the basis of one-pot oxidative cyclization of (E)-6-aryl-1,1,1-trifluorohex-5-ene-2,4-diones via a bromination/dehy-drobromination approach. This strategy was also applied for the preparation of 2-phenyl-6-polyfluoroalkyl-4-pyrones and their 5-bromo derivatives. Conditions of chemoselective enediones bromination were found and the key intermediates of the cyclization of bromo-derivatives to 4-pyrones were characterized. Synthetic application of the prepared 4-pyrones has been demonstrated for the construction of biologically important CF3-bearing azaheterocycles, such as pyra-zoles, pyridones, and triazoles. © 2021 by the authors. Licensee MDPI, Basel, Switzerland.Funding: This research was funded by the Russian Science Foundation, grant number 18-13-00186

Dust density waves in a dc flowing complex plasma with discharge polarity reversal

We report on the observation of the self-excited dust density waves in the dc discharge complex plasma. The experiments were performed under microgravity conditions in the Plasmakristall-4 facility on board the International Space Station. In the experiment, the microparticle cloud was first trapped in an inductively coupled plasma, then released to drift for some seconds in a dc discharge with constant current. After that the discharge polarity was reversed. DC plasma containing a drifting microparticle cloud was found to be strongly non-uniform in terms of microparticle drift velocity and plasma emission in accord with [Zobnin et.al., Phys. Plasmas 25, 033702 (2018)]. In addition to that, non-uniformity in the self-excited wave pattern was observed: In the front edge of the microparticle cloud (defined as head), the waves had larger phase velocity than in the rear edge (defined as tail). Also, after the polarity reversal, the wave pattern exhibited several bifurcations: Between each of the two old wave crests, a new wave crest has formed. These bifurcations, however, occurred only in the head of the microparticle cloud. We show that spatial variations of electric field inside the drifting cloud play an important role in the formation of the wave pattern. Comparison of the theoretical estimations and measurements demonstrate the significant impact of the electric field on the phase velocity of the wave. The same theoretical approach applied to the instability growth rate, showed agreement between estimated and measured values.Comment: 7 pages, 4 figure

A pulsed source of continuous variable polarization entanglement

We have experimentally demonstrated polarization entanglement using continuous variables in an ultra-short pulsed laser system at telecommunication wavelengths. Exploiting the Kerr-nonlinearity of a glass fibre we generated a polarization squeezed pulse with S2 the only non-zero Stokes parameter thus S1 and S3 being the conjugate pair. Polarization entanglement was generated by interference of the polarization squeezed field with a vacuum on a 50:50 beam splitter. The two resultant beams exhibit strong quantum noise correlations in S1 and S3. The sum noise signal of S3 was at the respective shot noise level and the difference noise signal of S1 fell 2.9dB below this value

Psychopathological manifestations of multiple meningiomas in the right hemisphere

The paper gives the data available in the literature on meningiomas and their psychopathological manifestations that occupy a central position in the clinical picture in almost every 5 patients with these tumors. The authors provide a clinical and psychopathological analysis of a female patient with multiple meningiomas in the right hemisphere: a giant meningioma in the posterior third of the falx, a large meningioma in the temporal region, and three small meningiomas in the frontal and parietal regions. The disease started as headache; however, psychopathological symptoms remained missed by physicians, such as emotional lability; personality changes leading to family dissension; lower criticism; spatial orientation problems; hypomnesia; left-sided visual inattention,occurred in parallel. Surgical treatment was performed by stages: the two largest meningiomas were removed at an 11-day interval, which presented a means of observing psychopathological changes after each operation. It is concluded that greater attention should be given to the psychopathological manifestations of the disease, which is important to make a primary diagnosis and to define further treatment policy

Shear flow in a three-dimensional complex plasma in microgravity conditions

Shear flow in a three-dimensional complex plasma was experimentally studied in microgravity conditions using Plasmakristall-4 (PK-4) instrument on board the International Space Station (ISS). The shear flow was created in an extended suspension of microparticles by applying the radiation pressure force of the manipulation-laser beam. Individual particle trajectories in the flow were analyzed and from these, using the Navier-Stokes equation, an upper estimate of the complex plasma's kinematic viscosity was calculated in the range of $0.2$--$6.7~{\rm mm^2/s}$. This estimate is much lower than previously reported in ground-based experiments with 3D complex plasmas. Possible reasons of this difference are discussed.Comment: 5 pages, 4 figure