Conversion from electrocardiosignals to equivalent electrical sources on heart surface

In biomarker discovery, applying domain knowledge is an effective approach to eliminating false positive features, prioritizing functionally impactful markers and facilitating the interpretation of predictive signatures. Several computational methods have been developed that formulate the knowledge-based biomarker discovery as a feature selection problem guided by prior information. These methods often require that prior information is encoded as a single score and the algorithms are optimized for biological knowledge of a specific type. However, in practice, domain knowledge from diverse resources can provide complementary information. But no current methods can integrate heterogeneous prior information for biomarker discovery. To address this problem, we developed the Know-GRRF (know-guided regularized random forest) method that enables dynamic incorporation of domain knowledge from multiple disciplines to guide feature selection. Know-GRRF embeds domain knowledge in a regularized random forest framework. It combines prior information from multiple domains in a linear model to derive a composite score, which, together with other tuning parameters, controls the regularization of the random forests model. Know-GRRF concurrently optimizes the weight given to each type of domain knowledge and other tuning parameters to minimize the AIC of out-of-bag predictions. The objective is to select a compact feature subset that has a high discriminative power and strong functional relevance to the biological phenotype. Via rigorous simulations, we show that Know-GRRF guided by multiple-domain prior information outperforms feature selection methods guided by single-domain prior information or no prior information. We then applied Known-GRRF to a real-world study to identify prognostic biomarkers of prostate cancers. We evaluated the combination of cancer-related gene annotations, evolutionary conservation and pre-computed statistical scores as the prior knowledge to assemble a panel of biomarkers. We discovered a compact set of biomarkers with significant improvements on prediction accuracies. Know-GRRF is a powerful novel method to incorporate knowledge from multiple domains for feature selection. It has a broad range of applications in biomarker discoveries. We implemented this method and released a KnowGRRF package in the R/CRAN archive.     

The Effect of I155T,K156Q,K156E and N186K Mutations in Hemagglutinin on the Virulence and Reproduction of Influenza A/H5N1 Viruses

Molecular Biology - The continued circulation of influenza A virus subtype H5 may cause the emergence of new potential pandemic virus variants, which can be transmitted from person to person. The...     

Intensity of lipid peroxidation and antioxidant protection system indices during re-adaptation period after long-term space flights at the international space station

In the blood serum of seventeen members of crews which participated in 14 orbital expeditions to the International Space Station with the duration of 125 to 217 days, during the pre-flight period and on the day of landing on the 1st, 7th and 14th days of the rehabilitation period (RP) the content of LPO products was determined, namely diene conjugates (DC), malon dialdehyde (MDA), shiffbases (SB) and the main lipid oxidant - tocopherol (TP). The group of astronauts who made landing in the Space Shuttle spacecraft (8 persons) and the group of astronauts who accomplished space mission in the Soyus TM spacecraft (9 persons) demonstrated a decrease in DC and MDA levels with a rise in TF concentration in the course of the rehabilitation period. Changes in the group of the American spacecraft astronauts were more pronounced. LPO inhibition during the rehabilitation period is recognized [treated] as an adequate reaction to the stress caused by re-adaptation to the ground conditions. Also are discussed probable mechanisms of intergroup differencies in LPO intensity degree: biomembrane phase state changing under the influence of overloads during de-orbiting and stress response intensity during landing in different types of spacecraft.     

Viable nonsense mutants for the SUP45 gene in the yeast Saccharomyces cerevisiae are lethal at increased temperature

Nonlethal nonsense mutations obtained earlier in the essential gene SUP45 encoding the translation termination eRFI factor in the yeast Saccharomyces cerevisiae were further characterized. Strains carrying these mutations retain the viability, since the full-length eRF1 protein is present in these strains, although in decreased amounts as compared to wild-type cells, together with a truncated eRF1. All nonsense mutations are likely to be located in a weak termination context, because a change in the stop codon UGAA (in the case of mutation sup45-107) to UAGA (sup45-107.2) led to the alteration of the local context from a weak to strong and to the lethality of the strain carrying sup45-107.2. All nonsense mutations studied are characterized by thermosensitivity expressed as cell mortality after cultivation at 37 degrees C. When grown under nonpermissive conditions (37 degrees C), cells of nonsense mutants sup45-104, sup45-105. and sup45-107 display a decrease in the amount of the truncated eRF1 protein without reduction in the amount of the full-length eRF1 protein. The results of this study suggest that the N-terminal eRF1 fragment is indispensable for cell viability of nonsense mutants due to the involvement in termination of translation.     

Improving the representation of peptide‐like inhibitor and antibiotic molecules in the Protein Data Bank

With the accumulation of a large number and variety of molecules in the Protein Data Bank (PDB) comes the need on occasion to review and improve their representation. The Worldwide PDB (wwPDB) partners have periodically updated various aspects of structural data representation to improve the integrity and consistency of the archive. The remediation effort described here was focused on improving the representation of peptide‐like inhibitor and antibiotic molecules so that they can be easily identified and analyzed. Peptide‐like inhibitors or antibiotics were identified in over 1000 PDB entries, systematically reviewed and represented either as peptides with polymer sequence or as single components. For the majority of the single‐component molecules, their peptide‐like composition was captured in a new representation, called the subcomponent sequence. A novel concept called “group” was developed for representing complex peptide‐like antibiotics and inhibitors that are composed of multiple polymer and nonpolymer components. In addition, a reference dictionary was developed with detailed information about these peptide‐like molecules to aid in their annotation, identification and analysis. Based on the experience gained in this remediation, guidelines, procedures, and tools were developed to annotate new depositions containing peptide‐like inhibitors and antibiotics accurately and consistently. © 2013 Wiley Periodicals, Inc. Biopolymers 101: 659–668, 2014.     

Macromolecular complexes of BSA with gelatin

This work studies the effect of the helix-coil transition in gelatin on the structure development in the complex forming water-gelatin-BSA system using dynamic light scattering, environment scanning electron microscopy, rheometry, differential scanning microcalorimetry, circular dichroism, fluorescence, and absorption measurements. It was established that the structure of the complexes formed and the mechanism of intermacromolecular interaction are different in the case of two conformation states of gelatin. Above the temperature of the conformational transition (40 °C) intermacromolecular interaction leads to collapse gelatin macromolecules and formation compact (30 nm in radius) BSA-gelatin complexes (～6:1, mole/mole), partial stabilization of the secondary structure (increase the mean helix content), and stabilization of BSA molecules against thermo aggregation. At the same time it does not leads to an appreciable change in the thermodynamic parameters of the thermal transitions for BSA and gelatin. Below the temperature of the conformation transition (at 18 °C) the interaction results in formation of the large (600-1000 nm in radius) complex particles due to trapping BSA molecules into the meshes of the gelatin network and, as consequence, a substantial increase in the storage and loss moduli of the system.     

Detection and quantification of Lyme spirochetes using sensitive and specific molecular beacon probes

Background  

Lyme disease, caused by Borrelia burgdorferi, affects a large number of people in both the USA and Europe. The mouse is a natural host for this spirochete and is widely used as a model system to study Lyme pathogenesis mechanisms. Since disease manifestations often depend upon the spirochete burden in a particular tissue, it is critical to accurately measure the bacterial number in infected tissues. The current methods either lack sensitivity and specificity (SYBR Green), or require independent analysis of samples in parallel to quantitate host and bacterial DNA (TaqMan). We have developed a novel molecular beacon-based convenient multiplex real-time quantitative PCR assay to identify and detect small numbers of B. burgdorferi in infected mouse tissues.     

Study of transplanted lichens with the use of physical methods: the case of <Emphasis Type="Italic">Xanthoria parietina</Emphasis> (L.) Th. Fr.

Electron paramagnetic resonance spectroscopy and inductively coupled plasma optical emission spectrometry were used to study the epiphytic lichen Xanthoria parietina (L.) Th. Fr. transplanted to natural and urbanized zones in the Moscow region. The combination of physical and lichenindication methods allowed us to determine periods as well as the magnitude of changes in the biophysical characteristics of the transplanted lichen in different environmental conditions. Electron paramagnetic resonance spectroscopy demonstrated that the number of paramagnetic centers in lichens transplanted to the natural zone did not change in comparison with initial value (2.6 ± 0.4)·10¹⁷ spin/mg) and remained stable after four weeks after transplantation. The number of paramagnetic centers in lichens transplanted to the urbanized zone increased by 1.1·10¹⁷ spin/mg by the end of the third week as compared with its initial value ((2.6 ± 0.4)·10¹⁷ spin/mg). Inductively coupled plasma optical emission spectrometry was used to measure concentration of iron, copper, manganese, magnesium, and zinc. We detected substantial changes in concentration of these elements during first four weeks after transplantation. For instance, concentration of copper in lichens transplanted to the urbanized zone increased from 7.5 ± 2.7 μg/g to 56.4 ± 8.6 μg/g by the end of the third week of the experiment.     

Developmental cycle and the cytomorphological characteristics of the oleandomycin producer Streptomyces antibioticus

The developmental cycle and cytomorphological features of the industrial strain OL-1 and its variant 0968 of the oleandomycin-producing organism were studied. Variant 0968 was obtained as a result of exposure of the spores of strain OL-1 to UV light. When grown under submerged conditions in flasks with the rich medium, the strains were characterized by a complete developmental cycle consisting of three generations of the hyphae. Every generation had a tendency for formation of submerged spores. The UV-induced variant differed from the industrial strain by higher levels of the antibiotic accumulation which correlated with higher rates of the spore germination. The strains were characterized by polymorphism of the mycelium and formation of submerged spores during their cultivation which is likely to prolong the antibiotic synthesis from 120 to 216 hours from the inoculation moment. The long-term selection of the oleandomycin-producing organism on the rich medium markedly changed the culture genotype and resulted in significant changes in the developmental cycle under submerged cultivation conditions. The data may be used for the microscopic control of the process of oleandomycin production.     

Increasing the effectiveness of ampicillin in combination with lysozyme

The effect of lysozyme (2 mg/kg) on pharmacokinetics of ampicillin (60 mg/kg) and the lymph nodes was studied in a model of experimental diffuse peritonitis in 52 dogs. The drugs were administered intramuscularly in single doses simultaneously with simulation of the pathological process. Under such conditions, lysozyme promoted an increase in the ampicillin concentration in the lymphatic system, blood and tissues and prolonged the antibacterial activity to 18 hours of the experiment. This resulted in retarding lympho- and hematogenic dissemination of the infection from the primary focus and lowered the infectious and toxic affection of the regional lymph nodes, thus securing their barrier and immunological function. With lysozyme used in combination with the antibiotic the immunomorphological zones of the lymph nodes appeared to be preserved and the volumetric proportion of macrophages increased. Then the volumetric proportion of the blast cells and the frequency of macrophagal and lymphocytic interactions also increased. The most pronounced cell interactions were observed in the distal (tracheobronchial) lymph nodes whose functions before the infection generalization were mainly immunological.