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About 7% of all cancer deaths are caused by pancreatic cancer (PCa). PCa is known for its lowest survival rates among all oncological diseases and heterogenic molecular profile. Enormous amount of genetic changes, including somatic mutations, exceeds the limits of routine clinical genetic laboratory tests and further stagnates the development of personalized treatments. We aimed to build a mutational landscape of PCa in the Russian population based on full exome next-generation sequencing (NGS) of the limited group of patients. Applying a machine learning model on full exome individual data we received personalized recommendations for targeted treatment options for each clinical case and summarized them in the unique therapeutic landscape.

The results of research in recent years indicate a widespread low intake of vitamin D, its deficiency or lack among the population of many countries around the world. It is of interest to study vitamin D status of the population living at different geographic latitudes and depending on socio-demographic characteristics. The aim of the research is to analyze vitamin D status of the adult population living in the Omsk Region over the age of 18 in different seasons of the year. Material and methods. Evaluation of vitamin D status has been carried out in 818 adult residents (325 men and 493 women) aged 18 to 92 years, the median of age - 49 (35; 63) years. Vitamin D status was determined by the level of [25 (OH) D] in serum by the method of immuno-chemiluminescent or electrochemiluminescent analysis. Design: cross-section (simultaneous) uncontrolled epidemiological study. Research period: 2017, from January to December. Results and discussion. 25.8±1.5% showed optimal vitamin D provision, insufficient vitamin content was found in 32.5±1.6% of studied participants, and deficit in 41.4±1.7%. The median level of 25(OH)D for all subjects was in the suboptimal sufficiency range and amounted to 22.17 (16.5; 30.3) ng/ml. The lowest level of the metabolite has been registered in patients over the age of 80 years - 16.5 (13.2-22.6) ng/ml, at the age of 70-79 years - 19.1 (12.9-26.9) ng/ml. In persons aged 18-60 years, the median concentrations were higher (22.2-24.8 ng/ml) and did not differ in the age groups. Deficiencies of varying degrees were most prevalent in age groups over 80, 70-79, and 50-59 years. Slightly better sufficiency of men compared with women has been revealed (p=0.052). Seasonal differences were found in the nature of vitamin D supply characterized by a deficit state from January to June [median 18.7 (13.9; 23.5) ng/ml] and a state of insufficiency from July to December [median 24.8 (17.8; 32.04) ng/ml]. The dependence of the level of vitamin D status on the number of sunshine days during the periods of 15-90 days preceding blood collection hasn't been established. Conclusion. The problem of insufficiency of vitamin D applies to all age groups of the adult population of the region of Western Siberia, especially those over 70 years of age. For the first half of the year, predominantly deficient states are characteristic, and for the period from July to December - the state of vitamin D insufficiency in the residents., Competing Interests: The authors declare no overt and potential conflict of interest related to the publication of this article., (Copyright© GEOTAR-Media Publishing Group.)

An increase in the proliferative activity of a shoot apical meristem (SAM) and the further accumulation of a pool of undifferentiated cells (fasciation) results in phyllotaxis changes. In the case of Arabidopsis thaliana, a typical spiral leaf arrangement is replaced by an opposite or verticillate one (depending on the level of a fasciation manifestation). Pistil development in mutant plants is accompanied by the appearance of a group of undifferentiated meristematic cells in its central part. The addition of N-1-naphthylphthalamic acid (NPA) causes an increase in the meristem volume and number of stipules in both mutant and control plants. The NPA effect on the floral morphogenesis results in a significant growth of meristemic cell pool. The interaction of different mechanisms of a meristem volume control is discussed.

Different effects of fasciation on the structure of blastozones and ultimately on the morphology of the plants of the two families investigated was detected. The results of this study demonstrate that in Arabidopsis thaliana phyllotaxis changes, leading to the formation of whorled leaf aestivation (two or four leaf in the whorl). We also demonstrated that in Pisum sativum the number of folioles of a compound leaf increased, the number of stipules also increased, and stipules can grow together and form a structure similar to the sheath of Gramineae. Our results demonstrated that a common manifestation of fasciations in Arabidopsis and Pisum is the formation of a flattened meristem, which extended along the same line (axes of fasciation).

Functionally, the dimeric human skeletal muscle chloride channel hClC-1 is characterized by two distinctive gating processes, fast (protopore) gating and slow (common) gating. Of these, common gating is poorly understood, but extensive conformational rearrangement is suspected. To examine this possibility, we used FRET (fluorescence resonance energy transfer) and assessed the effects of manipulating the common-gating process. Closure of the common gate was accompanied by a separation of the C-termini, whereas, with opening, the C-termini approached each other more closely. These movements were considerably smaller than those seen in ClC-0. To estimate the C-terminus depth within the cytoplasm we constructed a pair of split hClC-1 fragments tagged extracellularly and intracellularly respectively. These not only combined appropriately to rescue channel function, but we detected positive FRET between them. This restricts the C-termini of hClC-1 to a position close to its membrane-resident domain. From mutants in which fast or common gating were affected, FRET revealed a close linkage between the two gating processes with the carboxyl group of Glu²³² apparently acting as the final effector for both.

Chloride channels and transporters of the CLC gene family are expressed in virtually all cell types and are crucial in the regulation of membrane potential, chloride homeostasis and intravesicular pH. There are two gating processes that open CLC channels-fast and slow. The fast gating process in CLC channels has recently been linked to a small movement of a glutamate side chain. However, the molecular mechanism underlying the slow gating process is still elusive. Using spectroscopic microscopy, we observed a large backbone movement in the C terminus of the CLC-0 chloride channel that was functionally linked to slow gating. We further showed that the C-terminal movement had a time course similar to slow gating. In addition, a mutation known to lock the slow gate open prevented movement of the C terminus. When combined with recent structural information on the CLC C terminus, our findings provide a structural model for understanding the conformational changes linked to slow gating in CLC transport proteins.

Fluorescence resonance energy transfer (FRET) is a widely utilized optical technique for measuring small distances of 1-10 nm in live cells. In recent years, its application has been greatly popularized by the discovery of green fluorescent protein (GFP) and many improved variants which make good donor-acceptor fluorophore pairs. GFP-based proteins are structurally stable, relatively inert, and can be reliably attached to points of interest. The combination of easy access to the GFP-based FRET technique and its obvious usefulness in many applications can lead to complacency. Potential problems such as light contaminants, e.g., bleed-through and cross-talk, and inconsistent donor and acceptor concentrations are easily overlooked and can lead to errors in FRET calculation and data interpretation. In this article, we outline possible pitfalls of GFP-based FRET and approaches that address these issues, including a "Spectra FRET" technique that can be easily applied to live cell studies.

We report cloning and characterization of FCRL2, a novel human gene that belongs to the FcR family. The gene is closely linked and structurally similar to the recently identified FCRL/FREB/FcRX gene. The encoded protein is composed of three Ig-like domains and a C-terminal mucin-like domain containing a conserved alpha-helical motif with dileucine signals. Intraexonic splicing may generate two alternative transcripts, coding for isoforms with the third and fourth domains replaced by entirely different amino acid sequences. Like FCRL, the full-length isoform of FCRL2 is expressed intracellularly in transfected 293T cells. Expression analysis revealed FCRL2 mRNA only in placenta. The gene transcripts were not detected in lymphoid tissues or in the main leukocyte subsets isolated from peripheral blood. However, we found that FCRL2 is differentially expressed by transformed B cell lines. Of interest is also the finding that the gene expression may be up-regulated in the progression of melanocytic tumors.