Facile synthesis of 6-organyl-4-(trifluoromethyl)pyridin-2(1H)-ones and their polyfluoroalkyl-containing analogs.

The three-component cyclization of 3-polyfluoroalkyl-3-oxopropanoates and methyl ketones with ammonium acetate affords 6-organyl-4-(polyfluoroalkyl)pyridin-2(1H)-ones (organyl is alkyl, aryl, or hetaryl). The synthesized pyridones were evaluated for antifungal, antibacterial, and analgesic activity.

The soft X-ray monochromator at the SASE3 beamline of the European XFEL: from design to operation.

The SASE3 soft X-ray beamline at the European XFEL has been designed and built to provide experiments with a pink or monochromatic beam in the photon energy range 250-3000 eV. Here, the focus is monochromatic operation of the SASE3 beamline, and the design and performance of the SASE3 grating monochromator are reported. The unique capability of a free-electron laser source to produce short femtosecond pulses of a high degree of coherence challenges the monochromator design by demanding control of both photon energy and temporal resolution. The aim to transport close to transform-limited pulses poses very high demands on the optics quality, in particular on the grating. The current realization of the SASE3 monochromator is discussed in comparison with optimal design performance. At present, the monochromator operates with two gratings: the low-resolution grating is optimized for time-resolved experiments and allows for moderate resolving power of about 2000-5000 along with pulse stretching of a few to a few tens of femtoseconds RMS, and the high-resolution grating reaches a resolving power of 10 000 at the cost of larger pulse stretching.

[Gonococcal pharyngitis]. / Gonokokkovyi faringit.

A description of a clinical case of oligosymptomatic pharyngitis associated with Neisseria gonorrhoeae is presented. On the example of oligosymptomatic localized gonococcal pharyngitis in a sexually active young man, included in the risk group for extragenital forms of sexually transmitted infections, an advantage has been shown molecular biological diagnostic method. Study of the spectrum of microflora of the oropharynx and urethra with assessment sensitivity to antibacterial drugs of representatives of the genus Neisseria isolated during mixed infection oropharynx, demonstrated that non-pathogenic Neisseria species are resistant to cephalosporins III-IV generations. Unrecognized forms of oropharyngeal gonococcal infection, as a consequence of the complications of clinical and diagnostic identification when patients refer to an otolaryngologist or dermatovenerologist, can serve a reservoir of resistant N. gonorrhoeae and a source of intractable gonococcal infection.

The SASE1 X-ray beam transport system.

SASE1 is the first beamline of the European XFEL that became operational in 2017. It consists of the SASE1 undulator system, the beam transport system, and the two scientific experiment stations: Single Particles, Clusters, and Biomolecules and Serial Femtosecond Crystallography (SPB/SFX), and Femtosecond X-ray Experiments (FXE). The beam transport system comprises mirrors to offset and guide the beam to the instruments and a set of X-ray optical components to align, manipulate and diagnose the beam. The SASE1 beam transport system is described here in its initial configuration, and results and experiences from the first year of user operation are reported.

Effects of radiation damage in studies of protein-DNA complexes by cryo-EM.

Nucleic acids are responsible for the storage, transfer and realization of genetic information in the cell, which provides correct development and functioning of organisms. DNA interaction with ligands ensures the safety of this information. Over the past 10 years, advances in electron microscopy and image processing allowed to obtain the structures of key DNA-protein complexes with resolution below 4Å. However, radiation damage is a limiting factor to the potentially attainable resolution in cryo-EM. The prospect and limitations of studying protein-DNA complex interactions using cryo-electron microscopy are discussed here. We reviewed the ways to minimize radiation damage in biological specimens and the possibilities of using radiation damage (so-called 'bubblegrams') to obtain additional structural information.

Erratum: Hanbury Brown-Twiss Interferometry at a Free-Electron Laser [Phys. Rev. Lett. 111, 034802 (2013)].

This corrects the article DOI: 10.1103/PhysRevLett.111.034802.

[Inhibiting the pro-tumor and transcription factor FACT: Mechanisms].

Conventional antitumor therapy is often complicated by the emergence of the so-called cancer stem cells (CSCs), which are characterized by low metabolic rates and high resistance to almost all existing therapies. Many problems of clinical oncology and a poor efficacy of current treatments in particular are ascribed to CSCs. Therefore, it is important to develop new compounds capable of eliminating both rapidly proliferating tumor cells and standard treatment-resistant CSCs. Curaxins have been demonstrated to manifest various types of antitumor activity. Curaxins simultaneously affect at least three key molecular cascades involved in tumor development, including the p53, NF-κB, and HSF1 metabolic pathways. In addition, studies of some curaxins indicate that they can inhibit the transcriptional induction of the genes for matrix metalloproteinases 1 and 8 (MMP1 and MMP8); the PI3K/AKT/mTOR signaling cascades; cIAP-1 (apoptosis protein 1) inhibitor activity; topoisomerase II; and a number of oncogenes, such as c-MYC and others. In vivo experiments have shown that the CSC population increases on gemcitabine monotherapy and is reduced on treatment with curaxin CBL0137. The data support the prospective use of FACT inhibitors as new anticancer drugs with multiple effects on cell metabolism.

Transcription-induced DNA supercoiling: New roles of intranucleosomal DNA loops in DNA repair and transcription.

RNA polymerase II (Pol II) transcription through chromatin is accompanied by formation of small intranucleosomal DNA loops. Pol II captured within a small loop drives accumulation of DNA supercoiling, facilitating further transcription. DNA breaks relieve supercoiling and induce Pol II arrest, allowing detection of DNA damage hidden in chromatin structure.

[Structure and function of histone chaperone FACT].

FACT is heterodimer protein complex and histone chaperone that plays an important role in maintaining and modifying chromatin structure during various DNA-dependent processes. FACT is involved in nucleosome assembly de novo and in the preservation and recovery of the nucleosome structure during and after transcription, replication and repair of DNA. During transcript elongation FACT reduces the height of the nucleosome barrier and supports survival of the nucleosomes during and after passage of RNA polymerase II. In this process FACT interacts with histone H2A-H2B dimer in nucleosomes, thus facilitating uncoiling of nucleosomal DNA from the octamer of histones; it also facilitates subsequent recovery of the canonical structure of the nucleosome after transcription. FACT also plays an important role in transformation of human cells and in maintaining the viability of the tumor cells.

[Evaluation of compensation abilities of kidneys using radionuclide examination].

The article presents the results of evaluation of compensation abilities of kidney based on the identification of volume of functioning renal tissue according to the single-photon emission scintigraphy (SPECT) and planar scintigraphy. The study included adult patients (65 patients with renal cell carcinoma, 32 patients with renal cysts and 20 patients without renal involvement) and pediatric patients aged 1 to 17 years (57 patients with various non-neoplastic lesions of the kidney). The following parameters were used: volume ratio of functioning tissue and the specific activities of the affected and contralateral kidneys, and the volumetric ratio of volumes estimated to the reference kidney volume depending on anthropomorphic data of patient (age and sex). It was found that the maximum compensatory renal reserve occurs in the case of reducing the volume of functioning tissue of the affected kidney and the simultaneous increase in the volume ofcontralateral kidney.

[The participation of salicylic and jasmonic acids in genetic and induced resistance of tomato to Meloidogyne incognita (Kofoid and White, 1919)].

Salicylic (SA) and jasmonic (JA) acids are the best known mediators of signal systems in plants. In this investigation the participation and character of interactions between SA- and JA-signals under the induced and genetic resistance of plants to nematodes was investigated on the model system tomato (Lycopersicon esculentum) and the root-knot nematode Meloidogyne incognita. This study demonstrates that application of JA and SA to tomato foliage induces systemic effects that suppress root-knot nematode infestation, inhibition of nematode reproduction, and also increased activity of LOX and PAL, the enzymes of biosynthesis of JA and SA. JA treatment did not inhibit Mz-mediated resistance, which suggests a lack of signaling conflicts between these two forms of defense.

Hanbury Brown-Twiss interferometry at a free-electron laser.

We present measurements of second- and higher-order intensity correlation functions (so-called Hanbury Brown-Twiss experiment) performed at the free-electron laser (FEL) FLASH in the non-linear regime of its operation. We demonstrate the high transverse coherence properties of the FEL beam with a degree of transverse coherence of about 80% and degeneracy parameter of the order 10(9) that makes it similar to laser sources. Intensity correlation measurements in spatial and frequency domain gave an estimate of the FEL average pulse duration of 50 fs. Our measurements of the higher-order correlation functions indicate that FEL radiation obeys Gaussian statistics, which is characteristic to chaotic sources.

In situ focus characterization by ablation technique to enable optics alignment at an XUV FEL source.

In situ focus characterization is demonstrated by working at an extreme ultraviolet (XUV) free-electron laser source using ablation technique. Design of the instrument reported here allows reaching a few micrometres resolution along with keeping the ultrahigh vacuum conditions and ensures high-contrast visibility of ablative imprints on optically transparent samples, e.g., PMMA. This enables on-line monitoring of the beam profile changes and thus makes possible in situ alignment of the XUV focusing optics. A good agreement between focal characterizations retrieved from in situ inspection of ablative imprints contours and from well-established accurate ex situ analysis with Nomarski microscope has been observed for a typical micro-focus experiment.

Spatial and temporal coherence properties of single free-electron laser pulses.

The experimental characterization of the spatial and temporal coherence properties of the free-electron laser in Hamburg (FLASH) at a wavelength of 8.0 nm is presented. Double pinhole diffraction patterns of single femtosecond pulses focused to a size of about 10×10 µm(2) were measured. A transverse coherence length of 6.2 ± 0.9 µm in the horizontal and 8.7 ± 1.0 µm in the vertical direction was determined from the most coherent pulses. Using a split and delay unit the coherence time of the pulses produced in the same operation conditions of FLASH was measured to be 1.75 ± 0.01 fs. From our experiment we estimated the degeneracy parameter of the FLASH beam to be on the order of 10(10) to 10(11), which exceeds the values of this parameter at any other source in the same energy range by many orders of magnitude.

[Elicitor activity of chitosan and arachidonic acid: their similarity and distinction].

Two elicitors-chitosan and arachidonic acid-induced the same defense responses in potatoes, stimulating the processes of wound reparation and inducing the formation of phytoalexins, inhibitors of proteinase, and active forms of oxygen. However, chitosan induced the defense potential of plant tissues at concentrations higher than those of arachidonic acid. The protective action of chitosan was defined by two parameters, i.e., the ability to induce the immune responses in plant tissues and to exhibit a toxic effect on the pathogen development, causing late blight and seedling blight, whereas the elicitor effect of arachidonic acid depended on its ability to induce the defense potential of plant tissues only.

[Involvement of salicylic acid in induction of nematode resistance in plants].

The role of salicylic acid (SA) as a possible signaling component in the case of the infection of plants with nematodes has been studied using a model system consisting of the tomato (Lycopersicon esculentum (Mill.) and race 1 of the gall eelworm Meloidogyne incognita (Kofoid and White, 1919; Chitwood, 1949). The pre-planting SA treatment of tomato seeds results in an increased nematode resistance of susceptible tomato cultivars; the protective effect is higher in the case of SA combined with chitosan, a biogenic elicitor of plant resistance. The studied preparations stimulate the growth and development of the plants. The increase in the resistance of tomato plants is related to the increased activity of phenylalanine ammonia-lyase and an increased SA content in plant tissues infected with nematodes; both these factors significantly influence nematode development.

[Wound repair in plant tissues (Review)].

Signaling systems responsible for repair processes in plants and manifestation of defensive effects in plant tissues were analyzed. Special attention was given to jasmonic acid, a mobile systemic repair signal, as well as to jasmonate biosynthesis and signal transport to the areas where protective responses of plants are induced. The main defense responses of potato tubers induced by wounding were considered.

[Chymotrypsin and trypsin inhibitor isolated from potato tubers].

Potato Kunitz-type chymotrypsin inhibitor (PKCI-23) was isolated from potato tubers (Solanum tuberosum L., Zhukov's Jubilee breed) and purified to a homogenous state. The protein was purified by gel-filtration chromatography and ion-exchange chromatography using Sephadex G-75 and CM-Sepharose CL-6B, respectively. PKCI-23 protein has been shown to inhibit both chymotrypsin and trypsin with equal efficacy, forming equimolar complexes with these enzymes. However, much weaker inhibitory effect of PKCI-23 has been observed for Carlsberg subtilisin. The N-terminal 20 amino acid sequence of PKCI-23 has been sequenced. PKCI-23 has been shown to suppress, with different efficacy, the growth and development of pathogenic microorganisms Fusarium culmorum (Wm. G. Sm.) Sacc. and Phytophtora infestans (Mont.) de Bary that infect potato.

[Immunomodulating activity of chitosan derivatives with salicylic acid and its fragments].

A study of biological activity of the derivatives of the chitin-chitosan oligomer with salicylic acid and its fragments showed that chitosan salicylate actively protected potato tubers against Phytophthora infestans but sharply inhibited reparation of potato tissues. N-(2-Hydroxybenzyl)chitosan exhibited good protective properties but did not influence wound reparation. N-(2-Hydroxy-3-methoxybenzyl)-N-pyridox-chitosan, which contained the pyridoxal and 2-hydroxy-3-methoxy fragments, was the most efficient, stimulating both defense against late blight and wound reparation in potato tissues.