Molecular Mechanisms of Spinocerebellar Ataxia Type 17.

Spinocerebellar ataxia type 17 (SCA17) is a hereditary neurodegenerative disorder characterized by progressive motor and cognitive decline, leading to severe disability and death. SCA17 is caused by a CAG repeat expansion mutation in the TBP gene, resulting in the production of an abnormally long polyglutamine tract, which classifies it as a polyglutamine disorder. At present, there is no effective treatment for SCA17, and existing therapies provide only symptomatic relief.

Design, Synthesis, and Biological Evaluation of (+)-Camphor- and (-)-Fenchone-Based Derivatives as Potent Orthopoxvirus Inhibitors.

In this work, a library of (+)-camphor and (-)-fenchone based N-acylhydrazones, amides, and esters, including para-substituted aromatic/hetaromatic/cyclohexane ring was synthesized, with potent orthopoxvirus inhibitors identified among them. Investigations of the structure-activity relationship revealed the significance of the substituent at the para-position of the aromatic ring. Also, the nature of the linker between a hydrophobic moiety and aromatic ring was clarified.

Generation of induced pluripotent stem cell line RCPCMi008-A derived from patient with spinocerebellar ataxia 17.

IPSC line RCPCMi004-8 was generated from skin fibroblasts collected from a male patient with spinocerebellar ataxia 17. The patient has expanded trinucleotide CAG repeats in the TBP (TATA-binding protein) gene on chromosome 6q27. The reprogramming of fibroblasts was performed with Sendai viruses containing Oct-4, Sox-2, Klf-4, and c-Myc.

"Necessity Is the Mother of Invention" or Inexpensive, Reliable, and Reproducible Protocol for Generating Organoids.

Organoids are three-dimensional (3D) cell cultures that replicate some of the key features of morphology, spatial architecture, and functions of a particular organ. Organoids can be generated from both adult and pluripotent stem cells (PSCs), and complex organoids can also be obtained by combining different types of cells, including differentiated cells. The ability of pluripotent cells to self-organize into organotypic structures containing several cell subtypes specific for a particular organ was used for creating organoids of the brain, eye, kidney, intestine, and other organs.

Revealing Color Forces with Transverse Polarized Electron Scattering.

The Spin Asymmetries of the Nucleon Experiment measured two double spin asymmetries using a polarized proton target and polarized electron beam at two beam energies, 4.7 and 5.9 GeV.

N-Aryl-7-hydroxy-5-oxo-2,3-dihydro-1H,5H-pyrido-[3,2,1-ij]quinoline-6-carboxamides. The Synthesis and Effects on Urinary Output.

Continuing a targeted search for new leading structures with diuretic action among tricyclic derivatives of hydroxyquinolines, which are of interest as potential inhibitors of aldosterone synthase, the synthesis of a series of the corresponding pyrido[3,2,1-]quinoline-6-carboxanilides was carried out by amidation of ethyl-7-hydroxy-5-oxo-2,3-dihydro-1,5-pyrido[3,2,1-]quinoline-6-carboxylate with aniline, aminophenols and -alkylsubstituted analogs with high yields and purity. The optimal conditions of this reaction are proposed; they make it possible to prevent partial destruction of the original heterocyclic ester and thereby avoid formation of specific impurities of 7-hydroxy-2,3-dihydro-1,5-pyrido[3,2,1-]quinolin-5-one. To confirm the structure of all substances obtained, elemental analysis, nuclear magnetic resonance (NMR) spectroscopy, and mass spectrometry were used.

The Study of Structure-Analgesic Activity Relationships in a Series of 4-Hydroxy-2,2-dioxo-1H-2λ⁶,1-benzothiazine-3-carboxylic Acid Toluidides and Xylidides.

In continuing the search for new analgesics among derivatives of 2,1-benzothiazines, a series of corresponding toluidides and xylidides of 4-hydroxy-2,2-dioxo-1-2λ⁶,1-benzothiazine-3-carboxylic acid has been synthesized by the reaction of ethyl 4-hydroxy-2,2-dioxo-1-2λ⁶,1-benzothiazine-3-carboxylate with equimolar amounts of mono- and dimethyl-substituted anilides in boiling dry xylene. Their structure has been confirmed by the data of elemental analysis, nuclear magnetic resonance (NMR) spectroscopy (¹Н and С), as well as mass spectrometry. All compounds obtained were subjected to pharmacological screening to identify their analgesic properties.

Polarization components in π0 photoproduction at photon energies up to 5.6 GeV.

We present new data for the polarization observables of the final state proton in the (1)H(γ,p)π(0) reaction. These data can be used to test predictions based on hadron helicity conservation and perturbative QCD. These data have both small statistical and systematic uncertainties and were obtained with beam energies between 1.

Search for effects beyond the born approximation in polarization transfer observables in e(over→)p elastic scattering.

Intensive theoretical and experimental efforts over the past decade have aimed at explaining the discrepancy between data for the proton electric to magnetic form factor ratio, G(E)/G(M), obtained separately from cross section and polarization transfer measurements. One possible explanation for this difference is a two-photon-exchange contribution. In an effort to search for effects beyond the one-photon-exchange or Born approximation, we report measurements of polarization transfer observables in the elastic H(e[over →],e(')p[over →]) reaction for three different beam energies at a Q(2)=2.

Recoil polarization measurements of the proton electromagnetic form factor ratio to Q2 = 8.5 GeV2.

Among the most fundamental observables of nucleon structure, electromagnetic form factors are a crucial benchmark for modern calculations describing the strong interaction dynamics of the nucleon's quark constituents; indeed, recent proton data have attracted intense theoretical interest. In this Letter, we report new measurements of the proton electromagnetic form factor ratio using the recoil polarization method, at momentum transfers Q2=5.2, 6.

Ethyl 2-(4-hydr-oxy-1-methyl-2-oxo-1,2-dihydro-quinolin-3-yl)acetate.

In the title compound, C(14)H(15)NO(4), the bicyclic fragment and the ester group form a dihedral angle of 86.7 (2)°. Inter-molecular O-H⋯O and C-H⋯O hydrogen bonding connects mol-ecules into a helix along the crystallographic b axis.

2-Bromo-methyl-N-isopropyl-7,8-dimeth-oxy-1,2-dihydro-1,3-oxazolo[3,2-a]quinoline-4-carboxamide.

In the title compound, C(18)H(21)BrN(2)O(5), conjugation between the π-donating N-C-O fragment and the π-withdrawing carbonyl group results in considerable redistribution of the electron density within the dihydropyridinol ring. This effect is also promoted by the formation of an intra-molecular N-H⋯O hydrogen bond. The five-membered heterocycle is disordered over two envelope conformations in a 0.

[Method of enhancing the diagnostic information value of the atrial vectorcardiogram].

An automated differentiation of the P loop from other VCG loops, its 20-fold magnification, visualization, and computation of its major spatial and projection parameters have been made possible, giving precise information on its configuration, duration, the direction of recording, as well as relative positions and directions of its instantaneous vectors. Digital computerization of the traces has produced different vector and scale characteristics of the spatial Pxyz loop.

[Spatial parameters of the automatically reproduced QRS loop of the VCG in healthy subjects].

The findings of the VCG automatic construction in 55 healthy subjects with different axial and positional variants of ECG were analyzed . The applied method of the automatic corrected VCG construction has shown that QRS loop morphology coincides with the classical forms of VCG described before in healthy persons. The data of the automatic calculations of spatial characteristics demonstrated the orientation stability according to the angle--azimuth, max QRSxyz , S/2 QRSxyz and the integral vector-- AQRSxyz , i.

[Method for the automated mapping of 35 ECG leads].

The method of recording the ECGs, inputting them into a computer and automatic analysis of 35 ECG leads is described. The proposed method largely diminishes the time expenditure and difficulties in obtaining and analysing 35 ECG lead mapping grams, as the computer makes all measurements and calculations and produces a final document.

[Spatial characteristics of the P loop in normal subjects and in patients with an enlarged right atrium].

The studies performed have shown that: 1) using automatic reproduction of 10-20-fold magnified images of P-loop it is possible to learn its configuration, duration, recording direction, position and orientation of its moment vectors; 2) using digital computer list output of curves it is possible to determine numerical values of PXYZ-loop parameters and its vector and scalar characteristics; 3) for the diagnosis of right atrial dilatation (RAD) the assessment of vector values is more important than their orientation by azimuth and elevation angles; 4) the increase beyond normal (M + 2 sigma) of space vector values of PXYZ-loop - P0.25 greater than 0.16 mV, -Pmax greater than 0.

[Functioning of the systems of neuromediator inactivation in the brain terminals of rats chronically exposed to terephthalic acid and its dimethyl ester].

The chronic effect of terephthalic acid and its dimethyl ester on rats causes a significant decrease of uptake of norepinephrine by gray matter synaptosomes and activates the monoaminoxidase and catechol-O-methyltransferase in cerebral hemispheres.

[Indices of left ventricular hypertrophy based on data from the automatic mapping of 35 ECG leads].

The potential of the method of 35 ECG leads' automatic mapping in the diagnosis of left ventricular hypertrophy was assessed for the first time. A number of mapping indices closely correlating with the myocardial mass and the thickness of the left ventricular wall were found while studying 35 ECG leads' maps followed by computer processing, in 28 hypertensive patients and 6 normal subjects the hypertrophy degree of the left ventricle being determined by echocardiography and X-rays. The index of the total maximum of the R-waves among 7 vertical columns (7.

[Inhibition of noradrenaline and choline active capture by rat brain synaptosomes in the presence of terephthalic acid and its dimethyl ester].

The system of [14C] noradrenaline and [3H] choline trapping by rat brain cortex synaptosomes was studied under the effect of terephthalic acid and its dimethyl ester. Active transport of the labeled substances by synaptosome is established to be considerably inhibited under conditions of the inhalation action of terephthalic acid and its dimethyl ester on rats. A possible influence of the mentioned chemical compounds on the mechanism of the reverse trapping of the mediators is under discussion.