Comprehensive peripheral blood immunoprofiling reveals five immunotypes with immunotherapy response characteristics in patients with cancer.

The lack of comprehensive diagnostics and consensus analytical models for evaluating the status of a patient's immune system has hindered a wider adoption of immunoprofiling for treatment monitoring and response prediction in cancer patients. To address this unmet need, we developed an immunoprofiling platform that uses multiparameter flow cytometry to characterize immune cell heterogeneity in the peripheral blood of healthy donors and patients with advanced cancers. Using unsupervised clustering, we identified five immunotypes with unique distributions of different cell types and gene expression profiles.

Changes of the Concentration of Short-Chain Fatty Acids in the Intestines of Mice with Different Types of Obesity.

We studied the production of short-chain fatty acids (SCFA) by the intestinal microbiota in mice with obesity caused by a diet and a genetic defect in the leptin receptor gene. In mice, intestinal contents were examined and SCFA were quantitatively assayed by gas chromatography. SCFA concentration in the intestinal contents of mice with alimentary obesity model was significantly lower in the first phase of the experiment (day 14), and the change in their production in dynamics was fundamentally different from this process in the control group (standard diet).

TCF7L1 Controls the Differentiation of Tuft Cells in Mouse Small Intestine.

Continuous and rapid renewal of the intestinal epithelium depends on intestinal stem cells (ISCs). A large repertoire of transcription factors mediates the correct maintenance and differentiation of ISCs along either absorptive or secretory lineages. In the present study, we addressed the role of TCF7L1, a negative regulator of WNT signalling, in embryonic and adult intestinal epithelium using conditional mouse mutants.

Live Birth of a Healthy Child in a Couple with Identical mtDNA Carrying a Pathogenic c.471_477delTTTAAAAinsG Variant in the Gene.

Molybdenum cofactor deficiency type B (MOCODB; #252160) is an autosomal recessive metabolic disorder that has only been described in 37 affected patients. In this report, we describe the presence of an in-frame homozygous variant (c.471_477delTTTAAAAinsG) in the gene in an affected child, diagnosed with Ohtahara syndrome according to the clinical manifestations.

Study of the molecular-structural composition of alcoholic extracts of radio-induced potato tubers by mass spectrometry and EPR.

This article presents data on electron paramagnetic resonance (EPR) and mass spectrometric analysis of potato tubers, irradiated with gamma rays, in order to examine and identify changes in the molecular composition of organic matter following radiation exposure. The products of the Maillard reaction were compared with the products of intramolecular radiolysis of organic constituents of potatoes. The presence of free radicals was verified using EPR.

Evaluation of multiple reaction monitoring cubed performed by a quadrupole-linear ion trap mass spectrometer for quantitative determination of 6-sulfatoxymelatonin in urine.

Liquid chromatography (LC) - mass spectrometry quantitative analysis of substances in biological samples is usually performed in the multiple reaction monitoring (MRM) variant. In complex biological matrices, strong interferences can be observed when using the LC-MRM method. Interference levels can be significantly reduced by using LC - multiple reaction monitoring cubed (MRM).

Distinct populations of embryonic epithelial progenitors generate Lgr5 intestinal stem cells.

The adult intestinal stem cells (ISCs) are transcriptionally heterogeneous. As the mechanisms governing their developmental specification are still poorly understood, whether this heterogeneity reflects an early determination of distinct cellular sub-types with potentially distinct physiological functions remains an open question. We investigate the cellular heterogeneity within the mouse embryonic midgut epithelium at the molecular and functional levels.

Selection of efficient Taq DNA polymerase to optimize T-DNA genotyping method for rapid detection of mutant plants.

Plants harbor homologues of various animal genes involved in phosphorus metabolism, telomere biology and other cellular processes. Compared to experiments with many other multicellular organisms, research in the model plant takes advantage of short generation time and an ever increasing arsenal of genetic and transgenic tools, including large collections of T-DNA knockout and activation lines. The availability of thousands of publicly available transgenic lines provides a unique opportunity to address a number of important biological questions.

Non-radioactive TRF assay modifications to improve telomeric DNA detection efficiency in plants.

The length of telomeric DNA is often considered a cellular biomarker of aging and general health status. Several telomere length measuring assays have been developed, of which the most common is the Telomere Restriction Fragment (TRF) analysis, which typically involves the use of radioactively labeled oligonucleotide probes. While highly effective, this method potentially poses substantial health concerns and generates radioactive waste.

Id2 controls specification of Lgr5 intestinal stem cell progenitors during gut development.

The adult intestinal stem cells (ISCs), their hierarchies, mechanisms of maintenance and differentiation have been extensively studied. However, when and how ISCs are established during embryogenesis remains unknown. We show here that the transcription regulator Id2 controls the specification of embryonic Lgr5 progenitors in the developing murine small intestine.

[Role of Bacterial Adhesin RAPA1 in Formation of Efficient Symbiosis of Rhizobium leguminosarum with Bean Plants].

Bacterial adhesins, the proteins responsible for attachment of plant growth-promoting rhizobacteria to plant roots, are involved in formation of stable associative symbioses. In the present work enhanced expression of the rapA1 adhesin gene in Rhizobium leguminosarum PVu5 was shown to improve the efficiency of nodulation on bean roots inoculated with the modified strain. The rapA1 gene was cloned into the pJN105Turbo plasmid, this construct was used for transformation of R.

[Effect of D,L-buthionine-S,R-sulfoximine on the ratio of glutathione forms and the growth of tatar buckwheat calli].

We studied the intracellular content of reduced (GSH) and oxidized (GSSG) glutathione, glutathione reductase activity, glutathione-S-transferase, and ascorbate peroxidase in morphogenic and nonmorphogenic Tatar buckwheat calli during the culture cycle as well as under the treatment with D,L-buthionine-S,R-sulfoximine (BSO), an inhibitor of γ-glutamylcysteine synthase, the first enzyme of glutathione biosynthesis. We found that, during passaging, cultures only slightly differed in total glutathione content; however, the content of GSH was higher in the morphogenic culture, whereas the content of GSSG was higher in the nonmorphogenic culture. In the morphogenic callus, the glutathione-S-transferase activity was 10-20 times higher and the glutathione reductase activity, was 2-2.

Identification of proteins specifically interacting with YB-1 mRNA 3' UTR and the effect of hnRNP Q on YB-1 mRNA translation.

In this study, proteins specifically interacting with the 3' untranslated region (UTR) of mRNA of the multifunctional Y-box-binding protein 1 (YB-1) were identified. One of these, hnRNP Q, was shown to specifically interact with the regulatory element (RE) in YB-1 mRNA 3' UTR and to inhibit translation of this mRNA. Its binding to the RE was accompanied by displacement from this element of the poly(A)-binding protein (PABP), a positive regulator of YB-1 mRNA translation, and by enhanced binding of the negative YB-1 mRNA translation regulator - YB-1 itself.

Suburbanization and sustainability in metropolitan Moscow.

Although Soviet-era urban-growth controls produced relatively sustainable metropolitan development patterns, low-density suburban sprawl has accelerated markedly in modern Russia. Distinctive features of Moscow's development history are its greenbelt, which dates from 1935 and is becoming increasingly fragmented, proliferation of satellite cities at the urban fringe, conversion of seasonal dachas into full-time residences, the very exclusive Rublevo Uspenskoe Highway development, and today's crippling traffic congestion. The recent economic crisis has slowed development and actually increased the supply of “economy-class” single-family homes, for which there is much pent-up desire but insufficient credit availability to meet the demand.

[Synthesis and antiviral activity of ureides and carbamates of betulinic acid and its derivatives].

Ureides and carbamates of betulinic acid and its derivatives were prepared in good yields by interaction of betulinic acid, betulonic acid, and betulonic acid 3-oxime with amines, amino acids, and alcohols. Ureides of betulonic acid containing L-Val and L-Met residues were found to be effective against herpes simplex type 1 virus. The English version of the paper: Russian Journal of Bioorganic Chemistry, 2003, vol.

[Study of pharmacological properties of betulin bishemiphthalate].

The results of pharmacological tests showed that betulin bishemiphthalate possesses hepatoprotector, antioxidant, and immunotropic properties. Administered in combination with hydroxymethyluracil, that betulin bishemiphthalate prevented the loss of experimental animals upon irradiation.

Lupane triterpenes and derivatives with antiviral activity.

Betulin and betulinic acid have been modified at the C-3 and C-28 positions and the antiviral activity of derivatives has been evaluated in vitro. It was found that simple modifications of the parent structure of lupane triterpenes produced highly effective agents against influenza A and herpes simplex type 1 viruses.

[Synthesis and antiviral activity of hydrazides and substituted benzalhydrazides of betulinic acid and its derivatives].

New nitrogen-containing derivatives of betulinic and betulonic acids, hydrazides and N'-benzalhydrazides, were synthesized. Their antiviral activities toward of influenza A virus, herpes simplex type I virus, enterovirus ECHO6, and HIV-1 were studied in vitro. Betulinic acid 3-oxime was found to have the highest activity against the influenza virus.

[Synthesis of the lupane group triterpenoids and there hepatoprotective activity].

Hemisuccinates, hemiphthalates, acetylsalicylates, cinnamates, and p-methoxycinnamates of lupeol, betulin, and 3-O-acetylbetulin were synthesized via interaction with corresponding acid anhydrides or acid chlorides. A number of betulin esters in position 3 and 28 were shown to exhibit a pronounced hepatoprotective effect similar to that of betulin and silibor. These experimental data were in a good agreement with the computer prediction of their biological activity.