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BACKGROUND: According to the classic works of H. Selye, a variety of factors can impact humans and trigger a complex bodily response known as a stress reaction. This can lead to an imbalance in the body's regulatory physiological systems. AIM: To investigate the effects of a technogenic rotating electric field (REF) on the levels of carbohydrate-containing liver biopolymers in experimental animals. MATERIAL AND METHODS: A total of 54 rats were used in the experiment. The levels of sialic acids, mucoproteins, fucose, and -L-fucosidase were measured in the liver homogenate before the study, on the 10th and 20th day of the experiment. To ensure accurate results, the rats were first diagnosed using the open field method to determine their stress resistance levels. Based on the results, the rats were then divided into three groups: stress-resistant, stress-unstable, and ambivalent. RESULTS: By the 10th day of REF exposure, an increase in all the studied parameters in the liver homogenate in rats was observed indicating catabolic processes. Sialic acids concentration in stress-resistant, unstable and ambivalent rats increased by 14% (p=0.024), 29% (p=0.020) and 26% (p=0.021), respectively. Corresponding elevations of fucose concentration were 24% (p=0.019), 27% (p=0.019), 31% (p=0.019) while the activity of -L-fucosidase increased by 55% (p=0.024), in 63% (p=0.024) and 55% (p=0.011) in the abovementioned categories of rates. Mucoproteins concentrations increased by 58% (p=0.011) in stress-resistant, 76% (p=0.011) in stress-unstable and 65% (p=0.021) in stress-ambivalent rats. By the 20th day of the experiment, decomposition of carbohydrate-containing biopolymers slowed in all groups. When compared with the 10th day 10, sialic acids concentration decreased in stress resistant, unstable and ambivalent rats by 12% (p=0.041), 17% (p=0.021) and 20% (p=0.011), respectively. Corresponding decrease in of mucoproteins was 26% (p=0.011), 33% (p=0.024), and 32% (p=0.024). Fucose concentration increased by 34% (p=0.024) in stress-resistant, by 22% (p=0.024) in stress-unstable and by 28% (p=0.010) in stress-ambivalent rats. Correspondingly, -L-fucosidase activity increased by 15% (p=0.021), 46% (p=0.02) and 31% (p=0.011). CONCLUSION: The study's findings indicate that technogenic REF can alter the levels of carbohydrate-containing biopolymers in animal livers, leading to the activation of catabolic processes. The group of stress-unstable individuals exhibited the most significant catabolic processes. Our results may have implications for occupations exposures to REF.

The article describes a clinical case of familial neurofibromatosis type I. This diagnosis was made in a nine-month-old patient according to the diagnostic criteria recommended by the International Expert Committee on Neurofibromatosis. Clinicaly, there were hyperpigmented caf-au-lait spot on the skin, the presence of one plexiform neurofibroma, the father had a genetically confirmed diagnosis of neurofibromatosis type I. Also after birth, this patient was diagnosed with buphthalmos. A mutation in the Neurofibromin gene NFI leads to increased cell proliferation, with a rapidly progressive course, characterized by combined damage to the skin, eyes, nervous system and some internal organs, leading to neuroectodermal and mesodermal dysplasia. Neurofibromin is an intracellular protein in the human genome that regulates several pathways of growth control and plays a key role in the pathogenesis of congenital glaucoma associated with neurofibromatosis type I and plexiform neurofibroma. Plexiform neurofibroma originates from the sheaths of the peripheral nerves, often affects multiple nerves, is abundantly perfused, and is a benign neoplasm, but there is a lifelong risk of malignancy. On the other hand, congenital glaucoma is a relatively rare disease, usually due to infiltration of the anterior chamber angle by neurofibromas, closure of the angle by neurofibromatous-thickened ciliary body and choroid, fibrovascularization. The clinical picture of neurofibromatosis type I can be very variable, even among members of the same family. Under the influence of a combination of pathogenetic factors, an asymptomatic course is determined in one individual, while in another, the disease proceeds in a severe form, up to disability. Surgical treatment for isolated orbital plexiform neurofibroma is used to decompress the orbit and prevent malignancy of the tumor. It should be noted that due to the peculiarity of the structure of the tumor, its total removal is often not possible. In this case, mini-frontal access was used. After the intervention, exophthalmos regressed, ophthalmotonus returned to normal. The child was discharged in a satisfactory condition. Thus, the described clinical case is of particular interest, based on the combination of orbital plexiform neurofibroma and congenital glaucoma associated with neurofibromatosis type I.

The previously underestimated effects of commensal gut microbiota on the human body are increasingly being investigated using omics. The discovery of active molecules of interaction between the microbiota and the host may be an important step towards elucidating the mechanisms of symbiosis. Here, we show that in the bloodstream of healthy people, there are over 900 peptides that are fragments of proteins from microorganisms which naturally inhabit human biotopes, including the intestinal microbiota. Absolute quantitation by multiple reaction monitoring has confirmed the presence of bacterial peptides in the blood plasma and serum in the range of approximately 0.1 nM to 1 μM. The abundance of microbiota peptides reaches its maximum about 5h after a meal. Most of the peptides correlate with the bacterial composition of the small intestine and are likely obtained by hydrolysis of membrane proteins with trypsin, chymotrypsin and pepsin — the main proteases of the gastrointestinal tract. The peptides have physicochemical properties allowing them selectively pass the intestinal mucosal barrier and resist fibrinolysis. Proposed approach to the identification of microbiota peptides in the blood may be useful for determining the microbiota composition of hard-to-reach intestinal areas and for monitoring the permeability of the intestinal mucosal barrier.

AIM: This study aimed to investigate the possible effect of intravenous anesthesia (sedation) with propofol on the levels of several cytokines (interleukin [IL]-6, IL-8, IL-10, and tumor necrosis factors-) and S100B protein in the blood plasma of children aged 1 year with craniostenosis. MATERIALS AND METHODS: Twenty patients aged 112 months diagnosed with non-syndromic forms of craniosynostosis, who underwent magnetic resonance imaging (MRI) of the brain under propofol sedation, were classified according to ASA I-II class. Peripheral blood sampling was performed before and after the drug administration, followed by laboratory analysis. RESULTS: A significant increase was found in the serum level of IL-6 (p = 0.004) when intravenous sedation with propofol was used for 29 4.93 min. CONCLUSION: Short exposure of children aged 1 year with craniostenosis to hypnotic propofol during brain MRI significantly increased the level of the pro-inflammatory cytokine IL-6 in the blood plasma.

There is growing interest in the beneficial effects of immune system boosting through the administration of adjuvants, not only in acute infections such as COVID but also in chronic degenerative disorders that are potentially associated with infection. The best-known immunopotentiators are Freund’s complete adjuvant (FCA) and its relative Bacille Calmete–Guérin (BCG), both based onMycobacteriumspecies. The key pathogen-associated molecular patterns (PAMPs) in both FCA and BCG are muramyl dipeptides (MDPs and glucosaminyl-MDP, GMDP). We previously identified the evolutionarily conserved protein Y-box factor YB-1/YBX1 as a primary target for MDP/GMDP. Unlike other host receptors for PAMPs, YB-1 is a diffusible molecule, and we therefore explored whetherin vivoadministration of YB-1, rather than its PAMP ligands, might enhance the immune response to a bacterial antigen and/or influence survival in the face of bacterial infection. We report that mice receiving YB-1 plus GMDPin vivomount a significantly increased B cell response versus GMDP alone against a test antigen (Yersinia pestisV antigen), and that YB-1 administration alone significantly promotes survival in the face of lethal bacterial (Escherichia coli) challengein vivo. Independent confirmation is warranted because recombinant YB-1 and its ligands could hold great promise both as adjuvants and as therapeutics.

В статье рассматриваются особенности питания, физической подготовленности и отношения к спорту студентов КФ РЭУ им. Г.В. Плеханова, анализируется состояние физической подготовленности и вовлеченности в физкультурно-спортивную деятельность студентов.

The article provides a brief overview of the developed by the authors and approved methods of precision testing of various samples of NAP-V dynamic consumers and the main test results using these methods in various geographic, weather and operational conditions. One of the key advantages of the techniques is the use of technology for obtaining precision coordinates of control points by the method of long-baseline relative determinations and obtaining reference tracks of a dynamic consumer using the method of integer resolution of ambiguities of phase GNSS measurements.

Plants utilize a plethora of peptide signals to regulate their immune response. Peptide ligands and their cognate receptors involved in immune signaling share common motifs among many species of vascular plants. However, the origin and evolution of immune peptides is still poorly understood. Here, we searched for genes encoding small secreted peptides in the genomes of three bryophyte lineages-mosses, liverworts and hornworts-that occupy a critical position in the study of land plant evolution. We found that bryophytes shared common predicted small secreted peptides (SSPs) with vascular plants. The number of SSPs is higher in the genomes of mosses than in both the liverwort Marchantia polymorpha and the hornwort Anthoceros sp. The synthetic peptide elicitors-AtPEP and StPEP-specific for vascular plants, triggered ROS production in the protonema of the moss Physcomitrella patens, suggesting the possibility of recognizing peptide ligands from angiosperms by moss receptors. Mass spectrometry analysis of the moss Physcomitrella patens, both the wild type and the Δcerk mutant secretomes, revealed peptides that specifically responded to chitosan treatment, suggesting their role in immune signaling.

This manuscript collects all the efforts of the Russian Consortium, bottlenecks revealed in the course of the C-HPP realization, and ways of their overcoming. One of the main bottlenecks in the C-HPP is the insufficient sensitivity of proteomic technologies, hampering the detection of low- and ultralow-copy number proteins forming the "dark part" of the human proteome. In the frame of MP-Challenge, to increase proteome coverage we suggest an experimental workflow based on a combination of shotgun technology and selected reaction monitoring with two-dimensional alkaline fractionation. Further, to detect proteins that cannot be identified by such technologies, nanotechnologies such as combined atomic force microscopy with molecular fishing and/or nanowire detection may be useful. These technologies provide a powerful tool for single molecule analysis, by analogy with nanopore sequencing during genome analysis. To systematically analyze the functional features of some proteins (CP50 Challenge), we created a mathematical model that predicts the number of proteins differing in amino acid sequence: proteoforms. According to our data, we should expect about 100 000 different proteoforms in the liver tissue and a little more in the HepG2 cell line. The variety of proteins forming the whole human proteome significantly exceeds these results due to post-translational modifications (PTMs). As PTMs determine the functional specificity of the protein, we propose using a combination of gene-centric transcriptome-proteomic analysis with preliminary fractionation by two-dimensional electrophoresis to identify chemically modified proteoforms. Despite the complexity of the proposed solutions, such integrative approaches could be fruitful for MP50 and CP50 Challenges in the framework of the C-HPP.

Evaluation of epidemiologic risk factor in relation to lung cancer invoked by polycyclic aromatic hydrocarbons has been inconsistent. To address this issue, we conducted a prospective evaluation of new biomarkers for lung cancer classified according levels of idiotypic and anti-idiotypic antibodies against polycyclic aromatic hydrocarbons in human blood serum. The blood serums of 557 lung cancer patients and 227 healthy donors were analysis of these antibodies by ELISA. Collected data were regrouped and analyzed by gender, smoking, and age as predictors of risk lung cancer factors. Also, the data of lung cancer patients were additionally analyzed by stages and types of lung cancer, surgery, and chemotherapy. It was suggested to use ratio of idiotypic and anti-idiotypic antibodies rather than distinguish level each of them separately. The ratio of levels in healthy people was 3.32 times higher than in lung cancer patients. This approach gave more precisely results and great prognostic value. The logistic regression model (AUC = 0.9) and neural networks (AUC = 0.95) were built to compare lung cancer patients and healthy donors by predictors. The ELISA data of 49 people random sampled from the originally ELISA data and ELISA data of 52 coal miners as a group of lung cancer risk were confirmed logistic regression model. So, suggested idiotypic and anti-idiotypic antibodies against polycyclic aromatic hydrocarbons were not only shown difference between healthy donors and lung cancer patients also elicited group of lung cancer risk among healthy people.

It was shown that in the presence of the recombinant protein YB-1, the response of human leukemic monocytes THP-1 to stimulation with muramylpeptide GMDP and LPS was significantly reduced, which was manifested in a decrease of the relative content of mRNA encoding the following molecules: proinflammatory cytokine IL-1β, innate immunity receptors NOD2 and TLR4, their adapters RIP2 and MyD88, and the p105/p50 (NF-κB1) and p100/p52 (NF-κB2) subunits of the NF-κB transcription factor. The inhibiting effect of YB-1 protein also follows from the lower level of p65 protein (RelA NF-kB) in nuclei of cells stimulated with LPS and GMDP/LPS. Inactivation of the NOD2 gene in the THP-1 cells resulted in a decrease of IL-1β mRNA in response to GMDP, LPS, and GMDP/LPS. At the same time, inactivation of the YB-1 gene led to an increased relative content of IL-1β and other molecules’ mRNA upon stimulation with GMDP. However, in response to stimulation with LPS and GMDP/LPS the level of IL-1β mRNA decreased in comparison to the initial cells, which indicates that YB-1 is necessary for the induction of an optimal immune response. Thus, the data obtained indicate the involvement of YB-1 in the innate immunity receptor system as a negative regulator of NOD2 receptor activity.

Small heat shock proteins (sHSPs) control the proteins stability in the cell preventing their irreversible denaturation. While many mycoplasmas possess the sHSP gene in the genome, Acholeplasma laidlawii is the only mycoplasma capable of surviving in the environment. Here we report that the sHSP IbpA directly interacts with the key division protein FtsZ in A. laidlawii, representing the first example of such interaction in prokaryotes. FtsZ co-immunoprecipitates with IbpA from A. laidlawii crude extract and in vitro binds IbpA with K

The use of modern methods of microstratigraphic and planigraphic analyses allows the authors to speak about features of organizing life space in the Middle Paleolithic sites. The layer 6B at Saradj-Chuko grotto can be defined as an actively occupied Middle Paleolithic habitation site, where ancient humans were engaged in manufacture and use of obsidian tools. A tracelogical analysis allowed the authors to reconstruct various economic activities of ancient humans. For the first time for the Middle Paleolithic site in the northern slope of the central Caucasus, a tracelogical analysis was carried out taking into account the space distribution of tools over the site area, which allowed us to study features of human activity at different areas of the site. The new data are considered within a broad context of the Middle Paleolithic of the Caucasus, as well as the available data on economic activity and residential structures in various sites are analyzed.

This special event will focus on typical mistakes that all starting graduate students seem to make when they first start designing circuits. Many of these errors are simple and easily avoided if only they are pre-warned. These errors show up at different phases of design, simulation, layout and testing. Renowned speakers will share their experience and provide examples of their own mistakes!

Respiratory syncytial virus (RSV) is the major viral respiratory pathogen for human infants and children. Despite a severe global burden incurred by annual RSV epidemics, there is no licensed RSV vaccine. We have developed an RSV vaccine from a human RSV strain from which the gene for the viral M protein has been deleted (“Mnull RSV”). RSV infects airway cells and produces each of its proteins. The M protein is responsible for reassembling the various other synthesized viral proteins into new, intact virus. In the absence of the M protein, therefore, reassembly does not occur, and the Mnull RSV does not replicate. We vaccinated 2-week old infant baboons with Mnull RSV either intranasally (IN) or directly into the lung (intratracheal, or IT), then infected these animals by inoculating human RSV directly into the lung. IN vaccination induced inconsistent serum RSV neutralizing antibody (NA) responses, but provided moderate reductions in respiratory rates, overall signs of illness and viral replication in bronchoalveolar lavage (BAL) fluid following infection. Intratracheal vaccination induced much stronger RSV NA responses, which persisted for at least 4–6 months. Following RSV infection, animals vaccinated by the IT route had much greater reductions in tachypnea and work of breathing than animals vaccinated IN, and had undetectable amounts of virus in BAL fluids. These results support the further development of IT Mnull RSV vaccination to reduce the impact of RSV infection in humans.

We performed a computer search for the DSIP homologous structures in the protein data bases and found the KND peptide (WKGGDNASGE), which was closely structurally related to DSIP, corresponding to the 324–332 fragment of the human lysine-specific histone demethylase 3B (EC 1.14.11), and possibly was a prototype of the real endogenous DSIP. Previously, we compared some biological effects of DSIP and KND. Antioxidant, anticonvulsant, and behavioral effects of KND proved to be more pronounced than those of DSIP, suggesting the higher efficacy and therapeutic potential of KND and its derivatives. In this study, we synthesized new analogs of DSIP and KND and examined their detoxifying action after the treatment with the cisplatin cytostatin in comparative experiments in vivo on rodents. KND and several its analogs were found to decrease the cisplatin effects on the induced changes in masses of target organs. The correcting effects of the studied peptides on the cisplatin-induced hematological abnormalities, such as the changes in the leukocyte content in blood and thrombocytopenia, were revealed after their intranasal administration to animals in low doses. A decrease in a pronouncement of histological deviation from a norm was shown in the tissues of liver, kidney, and spleen. A significant hepatoprotective and nephroprotective effects of the studied peptides were also observed. Thus, the revealed antitoxic properties of DSIP, KND, and their analogs, could be a basis for the creation of drugs of lower toxicity in the anticancer treatment and therapy of medicinal hepatitis.

Over the past decade, tools of omics technologies have generated a large amount of data in various repositories, which are of interest for meta-analysis today. Now, researchers in the field of proteomics and peptidomics focus not on sequencing, but on functions performed by molecules and metabolic interactions, in which the proteins or peptides participate. As a result of a single LC-MS/MS analysis, several thousand unique peptides can be identified, each of which may be bioactive. A classic technique for determining the peptide function is a direct experiment. Bioinformatics approaches as a preliminary analysis of potential biological functions are an important step and are able to significantly reduce time and cost of experimental verification. This article provides an overview of computational methods for predicting biological functions of peptides. Approaches based on machine learning, which are the most popular today, algorithms using structural, evolutionary, or statistical patterns, as well as methods based on molecular docking, are considered. Databases of bioactive peptides are reported, providing information necessary to construct new algorithms for predicting biological functions. Attention is paid to the characteristics of peptides, on the basis of which it is possible to draw conclusions about their bioactivity. In addition, the report provides a list of online services that may be used by researchers to analyze potential activities of peptides with which they work.

Blood as connective tissue potentially contains evidence of all processes occurring within the organism, at least in trace amounts (Petricoin et al., 2006) [1]. Because of their small size, peptides penetrate cell membranes and epithelial barriers more freely than proteins. Among the peptides found in blood, there are both fragments of proteins secreted by various tissues and performing their function in plasma and receptor ligands: hormones, cytokines and mediators of cellular response (Anderson et al., 2002) [2]. In addition, in minor amounts, there are peptide disease markers (for example, oncomarkers) and even foreign peptides related to pathogenic organisms and infection agents. To propose an approach for detailed peptidome characterization, we carried out an LC-MS/MS analysis of blood serum and plasma samples taken from 20 healthy donors on a TripleTOF 5600+ mass-spectrometer. We prepared samples based on our previously developed method of peptide desorption from the surface of abundant blood plasma proteins followed by standard chromatographic steps (Ziganshin et al., 2011) [3]. The mass-spectrometry peptidomics data presented in this article have been deposited to the ProteomeXchange Consortium (Deutsch et al., 2017) [4] via the PRIDE partner repository with the dataset identifier PXD008141 and 10.6019/PXD008141.

The conditions for peptidome analysis of blood plasma were optimized and the efficacy of the proposed approach was compared with the methods described in the literature. The method implies solution of two main problems: inactivation of blood plasma proteases and dissociation of peptides from major blood plasma proteins, which they are quantitatively associated with. To solve these problems, we proposed a new method of sample preparation. The essence of the method is simultaneous denaturation of plasma proteins plus reduction and alkylation of thiol groups of Cys, which is achieved by heating a blood plasma sample (95°C) in the presence of sodium deoxycholate, tris(2-carboxyethyl)phosphine, and 2-chloroacetamide. After separation of peptides from proteins by ultrafiltration on microcentrifuge filters and removal of sodium deoxycholate, the peptides are identified by LC-MS/MS using a Q Exactive HF (Thermo Scientific) mass spectrometer. As a result of one LC-MS/MS run of the peptide mixture obtained from ~15 μL of blood plasma, 2257 peptide fragments of 867 proteins were identified, which is 1.5 times higher than the values achieved by using the generally accepted method of differential solubilization. Our immediate plans include the use of our approach for cataloguing human blood plasma peptides, as well as establishing the magnitude of individual variability and the features of the peptidome that are related to gender and age.

Strain-constant (clamped) electro-optic coefficients r 11 S of langasite La3Ga5SiO14 (LGS), langatate La3Ga5.5Ta0.5O14 (LGT), catangasite Ca3TaGa3Si2O14 (CTGS) and α-quartz are measured at 1540 nm in the frequency range of 3–25 MHz. Experimental ratio of clamped and unclamped electro-optic coefficients r 11 S / r 11 T is 0.97 for LGS, 0.91 for LGT, 0.31 for CTGS, and 0.49 for quartz. Most of direct electro-optic effect in LGS and LGT is associated with lanthanum ions: clamped electro-optic coefficient r 11 S in lanthanum-free CTGS is 14 times less than in LGS. Low piezoelectric contribution to unclamped electro-optic coefficient r 11 T makes LGS and LGT promising materials for electro-optic devices, whose performance can be deteriorated by piezoelectric effect, especially, for high-voltage optical voltage sensors.

Plant and animal cells contain pools of endogenous peptides, which are the degradation products of functionally active proteins. It is known that these peptides can possess biological activity; however, the functions of most of them are unknown. The goal of the present study was to estimate the antimicrobial potential of endogenous peptides resulting from the degradation of functional proteins in cells of the moss Physcomitrella patens. Earlier, 117 peptides possessing an antimicrobial potential predicted in silico have been identified in the peptidomes of three types of P. patens cells by mass spectrometry. In the present work, the antimicrobial activity of six of these peptides toward the gram-positive bacteria Bacillus subtilis SHgw and Clavibacter michiganensis pv. michiganensis and gram-negative bacteria Escherichia coli K12 and Xanthomonas arboricola 3004 has been revealed. The results have shown that three of six peptides inhibit the growth of the phytopathogenic bacteria X. arboricola and C. m. pv. michiganensis; four peptides inhibit the growth of the gram-negative bacterium E. coli K12, and one peptide inhibits the growth of the gram-positive bacterium B. subtilis. It has been found that the peptides inhibiting the bacterial growth are predominantly the fragments of ribosomal proteins. The work confirms the potential of the biological activity of peptides that are the degradation products of functional proteins.

Low-noise linear regulators are critical for power supply regulation of noise-sensitive circuits, such as ADCs, phaselocked loops, and other mixed-signal/RF system-on-a-chip designs. A low-noise low-dropout (LN-LDO) regulator using switched-RC bandgap reference and a multiloop, unconditionally stable error amplifier for output capacitorless operation is presented in this paper. A sample-and-hold switched-RC filter is developed to reduce the noise of the bandgap reference and drain-side modulated current-mode chopping technique is proposed to reduce the flicker (1/f) noise of the error amplifier. A switched capacitor notch filter is utilized to filter out the residual chopping ripple of the error amplifier. Thermal noise of the current reference circuit which is significant at such low noise levels is also reduced by using a low-area penalty passive RC filter. These techniques reduce the total integrated output noise of the LDO in the 10 Hz to 100 kHz band from 95.3 μV RMS down to 14.8 μV RMS . The LDO delivers a maximum load current of 100 mA with a dropout voltage of 230 mV and a quiescent current consumption of 40 μA. It achieves a power supply rejection of 50 dB at 10 kHz for a programmable output voltage range of 1-3.3 V. Fabricated in a 0.25 μm CMOS process, the LDO core occupies an area of 0.18 mm 2 .

Antimicrobial peptides (AMPs) are natural antagonistic tools of many bacteria and are considered as attractive antimicrobial agents for the treatment of bacteria with multidrug resistance. Lactic acid bacteria from the gastrointestinal tract of animals and human produce various AMPs inhibiting the growth of pathogens. Here we report the isolation and identification of novel Lactobacillus fermentum strain HF-D1 from the human gut producing AMPs which prevents the growth of P. aeruginosa and S. marcescens. The active fraction of peptides was obtained from the culture liquid by precipitation at 80% saturation of ammonium sulphate. For peptides identification, the precipitate was treated with guanidine hydrochloride to desorb from proteins, separated with ultrafiltration on spin columns with 10,000 MWCO, desalted with a reversed-phase chromatography and subjected to LC-MS/MS analysis. The in silico analysis of the identified 1111 peptides by using ADAM, CAMPR3 and AMPA prediction servers led to identification of the linear peptide with highly probable antimicrobial activity and further investigation of its antibacterial activity mechanism is promising. By using the dereplication algorithm, the peptide highly similar to non-ribosomal cyclic AMPs originally isolated from Staphylococcus epidermidis has been identified. This indicates that L. fermentum HF-D1 represents a novel strain producing antimicrobial peptides targeting P. aeruginosa and S. marcescens.

Globally, human respiratory syncytial virus (RSV) is a major cause of severe lower respiratory infection in infants and young children. There are no licensed vaccines despite the high worldwide disease burden. RSV fusion (F) glycoprotein vaccine is the most advanced candidate for maternal immunization. In this report, a baboon maternal immunization model was used to assess the immunogenicity and protection of infants against pulmonary challenge with human RSV/A. Vaccination in the third trimester produced high anti-RSV F IgG titers and virus-neutralizing antibodies. Infants born to immunized females had high levels of serum RSV antibodies that were comparable to maternal levels at birth and persisted for over 50 days with a half-life of 14–24 days. Furthermore, infants from immunized females and challenged with RSV/A were healthy, developed less severe disease, and had only mild pulmonary inflammatory changes whereas infants born to non-vaccinated females developed more severe disease with marked to moderate interstitial pneumonia, pulmonary edema, and bronchiolar obstruction. These results support the further development of the RSV F vaccine for maternal immunization.

Genomes contain millions of short (Physcomitrella patens(moss). Several distinct classes of sORFs that differ in terms of their position on transcripts and the level of evolutionary conservation are present in the moss genome. Over 5000 sORFs were conserved in at least one of ten plant species examined. Mass spectrometry analysis of proteomic and peptidomic datasets suggested that 584 sORFs located on distinct parts of mRNAs and long non-coding RNAs (lncRNAs) are translated, including 73 conservative sORFs. Translational analysis of the sORFs and main ORFs at a single locus suggested the existence of genes that code for multiple proteins and peptides with tissue-specific expression. Alternative splicing is likely involved in the excision of translatable sORFs from such transcripts. We identified a group of sORFs homologous to known protein domains and suggested they function as small interfering peptides. Functional analysis of candidate lncRNA-encoded peptides showed it to be involved in regulating growth and differentiation in moss. The high evolutionary rate and wide translation of sORFs suggest that they may provide a reservoir of potentially active peptides and their importance as a raw material for gene evolution. Our results thus open new avenues for discovering novel, biologically active peptides in the plant kingdom.

The aim of this study was to investigate the biology of cancer stem cells (CSC) from a metastatic tumor. Previously, we explanted the cells of rat ascites Zajdela hepatoma in vitro. We established a permanent monolayer cell line via selection of adhesive cells from multicellular floating islets. In the present work, we cloned these cells by a limiting-dilution method and established five novel clonal sublines of the hepatoma: three holoclonal sublines containing CSC and two meroclonal sublines. After a long-term cultivation (approximately 30 passages, freezing, and thawing), the cell of clonal sublines retained the features of CSC. They have a tumor-initiating potential and produce mainly holoclones upon recloning in the complete growth medium and large nonadhesive hepatospheres in the serum-free medium. Morphometric analysis showed that the cells of holoclonal and meroclonal sublines differed in the cell shape, area, nucleus size, and nuclear-cytoplasmic ratio. We have found for the first time that holoclonal cells of Zajdela hepatoma have a fibroblast-like morphology and form contacts with each other due to membrane protrusions. We suggest that the fibroblast-like morphology of CSC is an attribute of a metastatic tumor and demonstrates the capability of these cells for individual migration.

Bacterial cell wall muramyl dipeptide (MDP) and glucosaminyl-MDP (GMDP) are potent activators of innate immunity. Two receptor targets, NOD2 and YB1, have been reported; we investigated potential overlap of NOD2 and YB1 pathways. Separate knockdown of NOD2 and YB1 demonstrates that both contribute to GMDP induction of NF-κB expression, a marker of innate immunity, although excess YB1 led to induction in the absence of NOD2. YB1 and NOD2 co-migrated on sucrose gradient centrifugation, and GMDP addition led to the formation of higher molecular mass complexes containing both YB1 and NOD2. Co-immunoprecipitation demonstrated a direct interaction between YB1 and NOD2, a major recombinant fragment of NOD2 (NACHT–LRR) bound to YB1, and complex formation was stimulated by GMDP. We also report subcellular colocalization of NOD2 and YB1. Although YB1 may have other binding partners in addition to NOD2, maximal innate immunity activation by muramyl peptides is mediated via an interaction between YB1 and NOD2.

Serum samples (33 healthy women, 34 ovarian cancer, 28 colorectal cancer, 34 syphilis patients and 136 patients with various benign gynecological diseases) were analyzed by MALDI-TOF MS peptide profiling and respective predictive models were generated by genetic and supervised neural network algorithms. Classification models for pathology versus healthy control showed up to 100% sensitivity and specificity for all target diseases. However, the specificity dropped to unsatisfactory 25–40% in case of target versus nontarget disease diagnostics. Expansion of the control group to an artificial “nominal control” group by adding profiles of benign gynecological diseases considerably improved specificity of the models distinguishing ovarian cancer from healthy control and benign gynecological diseases. The suggested version of MALDI-TOF MS profiling of sera could be applied to differentiate between cancers and benign neoplasms of the same localization which is a challenging task for classical methods. To increase the specificity of diagnostic methods based on peptidome analysis of blood samples, it is necessary to identify sets of concrete peptide structures which qualitatively or quantitatively differ among patients with different diseases.

We apply numerical simulation to understand the effect of heating conditions on melt convection in an industrial Ky furnace. The direct numerical simulation (DNS) approach was used to investigate the features of melt flow during the seeding stage. Two different cases of Kyropoulos furnace hot zone design were studied numerically, and results were compared with experimental data to understand the effect of modifications on melt convection.