Relationship between environmental pollution and genetic monitoring of human populations

The basis of genetic monitoring is the knowledge of laws of the spontaneous mutation process. These laws are determined for human chromosome and genome mutations by cytogenetic examination of newborns, infants with congenital defects, and the material of spontaneous abortions. Confidence intervals and all the necessary sample sizes were calculated when registering the mutagenic effects of different intensity in the general population as well as to the groups of closer contact with mutagens. Such calculations were made for controlling the spontaneous mutation process in lymphocytes of human peripheral blood on the basis of registering chromosome aberrations.     

Aberrant signaling pathways of the lung mesenchyme and their contributions to the pathogenesis of bronchopulmonary dysplasia

Bronchopulmonary dysplasia (BPD) is a chronic lung disease in infants born extremely preterm, typically before 28 weeks' gestation, characterized by a prolonged need for supplemental oxygen or positive pressure ventilation beyond 36 weeks postmenstrual age. The limited number of autopsy samples available from infants with BPD in the postsurfactant era has revealed a reduced capacity for gas exchange resulting from simplification of the distal lung structure with fewer, larger alveoli because of a failure of normal lung alveolar septation and pulmonary microvascular development. The mechanisms responsible for alveolar simplification in BPD have not been fully elucidated, but mounting evidence suggests that aberrations in the cross-talk between growth factors of the lung mesenchyme and distal airspace epithelium have a key role. Animal models that recapitulate the human condition have expanded our knowledge of the pathology of BPD and have identified candidate matrix components and growth factors in the developing lung that are disrupted by conditions that predispose infants to BPD and interfere with normal vascular and alveolar morphogenesis. This review focuses on the deviations from normal lung development that define the pathophysiology of BPD and summarizes the various candidate mesenchyme-associated proteins and growth factors that have been identified as being disrupted in animal models of BPD. Finally, future areas of research to identify novel targets affected in arrested lung development and recovery are discussed.     

The dynamics of cancer chromosomes and genomes

A key feature of cancer chromosomes and genomes is their high level of dynamics and the ability to constantly evolve. This unique characteristic forms the basis of genetic heterogeneity necessary for cancer formation, which presents major obstacles to current cancer diagnosis and treatment. It has been difficult to integrate such dynamics into traditional models of cancer progression. In this conceptual piece, we briefly discuss some of the recent exciting progress in the field of cancer genomics and genome research. In particular, a re-evaluation of the previously disregarded non-clonal chromosome aberrations (NCCAs) is reviewed, coupled with the progress of the detection of sub-chromosomal aberrations with array technologies. Clearly, the high level of genetic heterogeneity is directly caused by genome instability that is mediated by stochastic genomic changes, and genome variations defined by chromosome aberrations are the driving force of cancer progression. In addition to listing various types of non-recurrent chromosomal aberrations, we discuss the likely mechanism underlying cancer chromosome dynamics. Finally, we call for further examination of the features of dynamic genome diseases including cancer in the context of systems biology and the need to integrate this new knowledge into basic research and clinical applications. This genome centric concept will have a profound impact on the future of biological and medical research.     

Model structure of a fragment of biological knowledge (cell motility)

The aim of the study is to contribute to a better understanding of some aspects of the structure of biological knowledge and to make clearer to what extent the methods of reasoning may be useful in this field when only qualitative information is available. A fragment of biological knowledge (theory of cell motility) is analysed from the logico-methodological point of view as a coherent system and the possibility of its formal representation is investigated. The analysis is based on distinguishing the main objects and their features (attributes) of which a given piece of knowledge is composed and on the values which these features may display. The features are interconnected by relations (in which various number of arguments appear) and these relations constitute the main (general, higher level) laws of a given fragment of knowledge (theory). Values of attributes are also mutually connected and these relations correspond to the detailed (lower level) laws. A computer system (in which Prolog language was used) enables to perform inference operations of progressive as well as regressive type. The main categories of reasoning procedures are described and illustrated by examples, namely a) search for conclusions which may be confronted with the actual knowledge in order to verify the system as a whole, b) formation of working hypotheses in the process of their empirical verification and explanation of facts and laws. The problem of development and modification of the system is also discussed.     

The natural background of chromosome anomalies in the bone marrow cells of mice and the control of vaccines for genotoxicity

The levels of chromosomal anomalies in marrow cells of mice kept under conventional conditions in the animal house of the Mechnikov Research Institute for Vaccines and Sera (Moscow) and under specific pathogen-free conditions were compared by the micronuclear and metaphasic methods. In the animals kept under specific pathogen-free conditions the occurrence of anomalies did not exceed the normal level; in the animals of the other group the level of cells with aberrations was 4-5 times higher. All detected aberrations in the chromosomal structure were unstable. The results obtained in this investigation indicate that under the conventional conditions existing in the animal house of a microbiological research institute mitogens of the biological nature may be present.     

The Drosophila Eip78c Gene Is Not Vital but Has a Role in Regulating Chromosome Puffs

We have generated a number of chromosomal aberrations that disrupt the early-late ecdysone-induced 78C puff gene (Eip78C, ecdysone-induced protein, FlyBase name for the E78 gene of STONE and THUMMEL 1993), which encodes the two members of the nuclear hormone receptor superfamily Eip78C-A and Eip78C-B. The aberrations include deletions of the ligand-binding/dimerization domain of both, inversions that split Eip78C-A but retain residual Eip78C-B expression, and a small deletion specific for Eip78C-B. We find that wild-type Eip78C functions are completely dispensable for normal development under laboratory conditions. However, we show that Eip78C-B is required for the maximal puffing activity of a subset of late puffs (63E and 82F) since these puffs are reduced in size in Eip78C-B mutant backgrounds. Paradoxically the same late puffs are reduced, as well as at least one other, when the Eip78C-B cDNA is overexpressed from a heat shock promoter. These data indicate either that Eip78C function is redundant or that it plays a subtle modulating role in the regulation of chromosome puffing.     

Sendai virus vectors as an emerging negative-strand RNA viral vector system

The power to manipulate the genome of negative-strand RNA viruses, including the insertion of additional non-viral genes, has led to the development of a new class of viral vectors for gene transfer approaches. The murine parainfluenza virus type I, or Sendai virus (SeV), has emerged as a prototype virus of this vector group, being employed in numerous in vitro as well as animal studies over the last few years. Extraordinary features of SeV are the remarkably brief contact time that is necessary for cellular uptake, a strong but adjustable expression of foreign genes, efficient infection in the respiratory tract despite a mucus layer, transduction of target cells being independent of the cell cycle, and an exclusively cytoplasmic replication cycle without any risk of chromosomal integration. In this review we describe the current knowledge of Sendai virus vector (SeVV) development as well as the results of first-generation vector applications under both in vitro and in vivo conditions. So far, Sendai virus vectors have been identified to be a highly efficient transduction tool for a broad range of different tissues and applications. Future directions in vector design and development are discussed.     

The connection between ribophagy, autophagy and ribosomal RNA decay

Ribosomes are essential components of all cells. A large body of knowledge has been accumulated regarding ribosome synthesis and assembly; however, the pathways of normal ribosome turnover, especially rRNA decay, are not known. Some information on ribosome recycling derives from studies on starved yeast cells that use a specialized type of autophagy, called ribophagy, to differentially target ribosomes for degradation. We found that Arabidopsis RNS2, a conserved ribonuclease of the RNase T2 family, is necessary for normal decay of rRNA. Mutants lacking RNS2 activity have longer-lived rRNA, accumulate RNA in the vacuole and show constitutive macroautophagy. Thus, it is clear that normal rRNA decay is necessary to maintain cellular homeostasis. These phenotypes and the subcellular localization of RNS2 in the endoplasmic reticulum and the vacuole suggest that RNS2 participates in a ribophagy-like mechanism that targets ribosomes for recycling under normal growth conditions.     

The connection between ribophagy,autophagy and ribosomal RNA decay

Ribosomes are essential components of all cells. A large body of knowledge has been accumulated regarding ribosome synthesis and assembly; however, the pathways of normal ribosome turnover, especially rRNA decay, are not known. Some information on ribosome recycling derives from studies on starved yeast cells that use a specialized type of autophagy, called ribophagy, to differentially target ribosomes for degradation. We found that Arabidopsis RNS2, a conserved ribonuclease of the RNase T2 family, is necessary for normal decay of rRNA. Mutants lacking RNS2 activity have longer-lived rRNA, accumulate RNA in the vacuole and show constitutive macroautophagy. Thus, it is clear that normal rRNA decay is necessary to maintain cellular homeostasis. These phenotypes and the subcellular localization of RNS2 in the endoplasmic reticulum and the vacuole suggest that RNS2 participates in a ribophagy-like mechanism that targets ribosomes for recycling under normal growth conditions.     

Development of the skeleton in Japanese quail embryos

In the research fields of experimental embryology, teratological testing, and developmental engineering in avian species, a knowledge of normal embryonic development is necessary so that research may be performed efficiently and precisely. A series of normal stages based on external appearance has been established in both chicken and quail embryos. Those based on skeletal features, however, have not been elucidated. The present study newly established a series of normal stages for the development of the Japanese quail embryo skeleton. This series is composed of 15 stages determined by observing the timing of chondrification and calcification of the skeleton every 24 h, from 3 to 17 days of incubation. Cartilage and ossified bones were stained blue and red with Alcian blue 8GX and alizarin red S, respectively. These skeletogenous stages of the Japanese quail embryo will be useful as a normal control not only in studies of experimental embryology, teratological testing, and developmental engineering, but also in the analysis of mutant embryos with skeletal abnormalities.     

Spontaneous chromosome aberrations in human somatic cells

Conclusion In conclusion it is necessary to say that at present, we cannot consider whether there may be a geographical difference in frequency of spontaneous chromosome aberrations in somatic cells. For that purpose, a very abundant experimental material is required, as well as an improvement in methodology: what causes the difference in the results of various investigators; what methodical principles should be used for collection of data.Important factors in the differences of frequencies of spontaneous chromosome aberrations are likely to be the conditions of cultivation and making the preparations, as well as the methods of scoring the chromosome aberrations. The international standardisation of the cultivation conditions and of the estimates of chromosome aberrations is needed for the further study of the rate and reasons of the spontaneous mutation process in somatic cells.     

Psychological Problems Of Dialogue In Light Of The Ideas Of M. M. Bakhtin And A. A. Ukhtomskii

Comparative examination of the scientific and philosophical ideas of Mikhail Mikhailovich Bakhtin and Aleksei Alekseevich Ukhtomskii is of interest from the standpoint of both the psychological theory of communication and the practice of psychological counseling, psychotherapy, and upbringing. Development of the applied areas of psychology poses the tasks of understanding the particular person and his individual problems and offering psychological assistance in the process of communication. To deal with these questions it is not sufficient to have scientific psychological training, i.e., knowledge of the general laws of personality development and communication; a capacity for personal communication as an aid to resolving human life problems is also necessary.     

The role of Src family kinases in egg activation

Solitary amoebae of Dictyostelium discoideum are frequently exposed to stressful conditions in nature, and their multicellular development is one response to environmental stress. Here we analyzed an aggregation stage abundant gene, krsA, homologous to human krs1 (kinase responsive to stress 1) to understand the mechanisms for the initiation of development and cell fate determination. The krsA- cells exhibited reduced viability under hyperosmotic conditions. They produced smaller aggregates on membrane filters and did not form aggregation streams on a plastic surface under submerged starvation conditions, but were normal in sexual development. During early asexual development, the expression of cAMP-related genes peaked earlier in the knockout mutants. Neither cAMP oscillation in starved cells nor an increase in the cAMP level following osmotic stress was observed in krsA-. The nuclear export signal, as well as the kinase domain, in KrsA was necessary for stream formation. These results strongly suggest that krsA is involved in cAMP relay, and that signaling pathways for multicellular development have evolved in unison with the stress response.     

Use of unstable chromosome aberrations for biological dosimetry after the first postirradiation mitosis

The loss of unstable chromosome aberrations after the first postirradiation mitosis makes their use difficult in radiation dosimetry. We describe here a method which, in a cell population observed at this stage, allows retrospective estimation of the frequencies of the unstable aberrations induced at the time of irradiation, and their use as a dosimeter. The laws controlling the behavior of unstable aberrations during mitosis were defined from a large-scale experiment on irradiated human lymphocytes. For cells undergoing the first, second, or third mitosis after irradiation, relationships were determined between the frequency, at irradiation time, of acentric fragments not arising from formation of dicentrics or rings, and the ratio of dicentrics and centric rings appearing without acentric fragments to the total number of dicentrics plus rings. On the basis of this ratio, the method described here provides an assessment of the postirradiation mitotic activity in a cell population. This assessment permitted estimation of the cell distribution and frequency of dicentrics plus centric rings, and of the frequency of acentric fragments at the time of irradiation. The use of this method for retrospective dosimetry after whole-body irradiation under various conditions of exposure is illustrated.     

Mathematical models, explanation, laws, and evolutionary biology

It is commonly agreed in the literature on laws of nature that there are at least two necessary conditions for lawhood--that a law must have empirical content and that it must be universal. The main reason offered for the requirement that laws be empirical is as follows: a priori statements are consistent with any imaginable set of observations, so they cannot be informative about the world and therefore they cannot provide explanations. However, we care about laws because we think that laws provide explanations and allow us to make predictions. Thus, if one of the functions of laws is to provide explanations and a priori propositions cannot fulfill this function, they cannot properly be viewed as laws. In this paper, I will aim to show that this argument for the claim that laws must be empirical does not work.     

Effects of high temperatures on chromosomes of normal and transformed human cells

The effects of the high temperature on the chromosome of normal and transformed human cells were examined using a temperature gradient incubator (T.G.I., Model TN-212) in culture. The cell nucleus were damaged, specifically fragmentation occurred under the hyperthermic treatments. The diploid cells were passaged at three different temperature conditions ranging from 39.0-41.5 degrees C. It was found that the polyploid cells (predominantly tetraploid) were increased in these conditions compared with the cells cultured at 37 degrees C. We observed the chromosomal aberrations (break, stickiness, fragmentation, etc.) in the cells treated with high temperature for the various periods of time. The results indicated that the transformed cells were more high-temperature sensitive than the normal cells with respect to the chromosomal aberrations. The trend was seen in this experiment, in which the chromatid breaks of HAIN-55 and MKN-1 cell strains occurred more on the large chromosomes such as the ones in group A, B and C under the hyperthermic treatments.     

Psychological Laws of the Social Development of the Personality in Ontogeny

Cultivation of the new man as an individual person is a requirement of developed socialist society. At the present stage of socialist construction, which entails a qualitatively new level of decision making [in confronting] socioeconomic and political problems, the role of the human factor in all spheres of the vital activity of society becomes especially urgent, and the importance of people's maintaining a responsible social position becomes greater. The achievements in public education, science, and culture have made it both possible and necessary to concentrate attention not only on instruction but, most importantly, on cultivating the new man, who is "not merely the bearer of a specific sum of knowledge but, first and foremost, a citizen of socialist society"[7. P. 391. The need to deal with this problem has had an impact on the main areas of reform of the general educational and vocational training school, a reform based on a new level of psychological and pedagogical knowledge, and defines the tasks of further scientific inquiry. One of the most important tasks of psychology is to intensify study of the development of the personality, to discover the psychological laws of its development, and the conditions and mechanisms for accelerating the process of personal self-determination.     

Genome-Wide Identification of Somatic Aberrations from Paired Normal-Tumor Samples

Genomic copy number alteration and allelic imbalance are distinct features of cancer cells, and recent advances in the genotyping technology have greatly boosted the research in the cancer genome. However, the complicated nature of tumor usually hampers the dissection of the SNP arrays. In this study, we describe a bioinformatic tool, named GIANT, for genome-wide identification of somatic aberrations from paired normal-tumor samples measured with SNP arrays. By efficiently incorporating genotype information of matched normal sample, it accurately detects different types of aberrations in cancer genome, even for aneuploid tumor samples with severe normal cell contamination. Furthermore, it allows for discovery of recurrent aberrations with critical biological properties in tumorigenesis by using statistical significance test. We demonstrate the superior performance of the proposed method on various datasets including tumor replicate pairs, simulated SNP arrays and dilution series of normal-cancer cell lines. Results show that GIANT has the potential to detect the genomic aberration even when the cancer cell proportion is as low as 5∼10%. Application on a large number of paired tumor samples delivers a genome-wide profile of the statistical significance of the various aberrations, including amplification, deletion and LOH. We believe that GIANT represents a powerful bioinformatic tool for interpreting the complex genomic aberration, and thus assisting both academic study and the clinical treatment of cancer.