Systemic analysis: Individual typological characteristics of the human body

Statistical analysis of the distribution of the mean somatometric, functional, and psychophysiological parameters in the total sample of subjects with the use of the χ² and λ tests and low, medium, and high habitual physical activity (HPA) levels (LHPA, MHPA, and HHPA, respectively) at different ontogenetic stages (junior and senior school students and young adults of both sexes) showed wide quantitative and qualitative ranges of psychophysiological individuality in a healthy population and demonstrated that it is reasonable to distinguish three typological groups or functional constitutional types (FT-1 corresponding to LHPA; FT-2, to MHPA; and FT-3, to HHPA). Typical first- and second-order parameters, as well as the results of third-order tests characterizing the current state, were determined for each FT. In order to comprehensively assess the constitutional type (synthetic constitution) of the subjects with low, medium, and high HPAs, the integrated analysis of the set of their characteristics was performed using the principles of polythetic (multi-variate) classification. The results obtained using multivariate statistical methods confirmed the basic postulate of the concept of typological variability of physiological individuality that a healthy human population is qualitatively heterogeneous in morphological, functional, and psychophysiological traits. The integrated physiological and statistical analyses of the results provided a scientific basis for three functional constitutional types (FT-1, FT-2, and FT-3) corresponding to three synthetic constitutional types (C 0-1, C 00, and C 01). These data indicate that the systemic (constitutional) approach to the estimation of individual typological characteristics confirm a high informativeness of partial constitution (FT-1, FT-2, and FT-3) in the human biological organization, and the set of characters selected for analysis allows the synthetic constitutional types to be adequately differentiated on a formal basis.     

Functional type of the constitution (systematic analysis of individual-typological characteristics of an organism)

Analysis of the statistical distribution of feature based chi2 and lambda criteria and average data somatometric, functional and psycho-physiological indices in the total sample of individuals with low, medium and high habitual physical activity (LHPA, M H PA and HHP A) at different stages of ontogenesis (the older preschool and early school children, boys and girls) has identified a fairly wide area of different quality and physiological individuality in a healthy population and the feasibility of allocating the three typological groups--functional constitution types (FTC-1 - LHPA, FTC-2 - MHPA, FTC-3 - HHPA). Set model parameters of the first and second order for each FTC, as well as performance tests of the third order, describing the current functional state. For the full specifications of the constitutional membership (synthetic constitution) of individuals with low, medium and high-held PDA integral assessment of their properties by using the principles polythetic (multidimensional) classification. Obtained by means of multivariate statistical methods results confirmed the postulate of the concept of typological variability of physiological individuality real different quality of healthy human population on the morphofunctional and psycho-physiological grounds and conducted a comprehensive physiological and statistical analysis of results allowed us to scientifically justify the selection of three functional types of constitution (PTC-1, FTC-2, FTC-3), corresponding to three types of synthetic constitutive (K 0-1, K 00, K 01). The data obtained show that the system (constitutional) approach to the evaluation of individual-typological characteristics of the organism confirms the high information private constitution(PTC-1, FTC-2, FTC-3) in human biological organization, and the selected feature set can adequately differentiate the synthetic constitutional types in a formal basis.     

Avoiding pitfalls in bone marrow engraftment analysis: a case study highlighting the weakness of using buccal cells for determining a patient's constitutional genotype after hematopoietic stem cell transplantation

Background aimsAn accurate and reliable assessment of bone marrow engraftment (BME) after hematopoietic stem cell transplantation (HSCT) is based on the ability to distinguish between recipient and donor cells at selected polymorphic short tandem repeat (STR) DNA loci. Buccal cells are an important source of DNA for determining the recipient's constitutional genotype, particularly in patients transplanted before the STR evaluation.MethodsGenomic DNA was extracted from the recipient buccal cells and from isolated CD3⁺ (T-cell lymphocyte) and CD33⁺ (myelocyte) cells after HSCT. BME analysis was performed using a STR-based polymerase chain reaction amplification method followed by fragment-size analysis for assessing the recipient-derived or donor-derived composition of cell lineage-specific peripheral blood DNA.ResultsWe identified three cases of complete buccal epithelial cell engraftment after HSCT detected by BME analysis, potentially leading to misinterpretation of testing results if these cells were used as the sole source for determining the recipient's genotype.ConclusionsThese cases suggest that complete engraftment of buccal epithelial cells may be a common finding in patients receiving HSCT, drawing attention to important issues such as the type of samples used for determining a patient's constitutional genotype that may confound testing results. This study also highlights the need for careful interpretation of the BME testing results in the context of the clinical findings.     

The relation between the variability of polygenic morphological and monogenic biochemical traits as exemplified by Karakul sheep

A quantitative method for investigation of relationship between polygenic and monogenic traits has been proposed. It is based on examination of relationship between frequencies of distribution classes of an adaptive quantitative trait and frequencies of certain genetic character in the same classes. The method permits to locate a gene marker within a space of quantitative trait values. Using adaptively significant morpho-anatomic traits, it is possible to estimate indirectly adaptive values of gene markers under consideration, since, in accordance with the concept of adaptive norm, "average" phenotypes have maximal fitness, whereas deviative phenotypes transgress the bounds of the optimum. As a genetical character, genotype of certain biochemical locus, individual heterozygosity range or interlocus combinations of alleles could be used. The method has been applied to newborn Astrakhan lambs. Principal component analysis has been used to obtain complex characterization for six constitutional characters. Some regularities in location of homo- and heterozygous genotypes of the transferrin locus within a space of morphological characters' values have been revealed.     

Nitric oxide as the mediator of the antiosteoporotic actions of estrogen, statins, and essential fatty acids

Estrogen, statins, and essential fatty acids and their metabolites can prevent osteoporosis. However, it is not certain how these three structurally different agents can have the same beneficial action. It is suggested that all three, in addition to their other modes of action in the prevention of osteoporosis, have the ability to augment constitutional (or endothelial) nitric oxide generation, which is known to be beneficial in osteoporosis. If so, it will be interesting to study whether nitric oxide donors and/or nitric oxide precursors can be given together with estrogen, statins, or essential fatty acids to potentiate their benefit in osteoporosis.     

Evolution versus constitution: differences in chromosomal inversion

We compared the chromosomal breakpoints of evolutionary conserved and constitutional inversions. Multicolor banding and human-specific bacterial artificial chromosomes were applied to map the breakpoints of constitutional pericentric inversions on human chromosomes 2 and 9. For the first time, we present a high-resolution analysis of the breakpoint regions, which are characterized by gene destitution, co-localization with fragile sites, multitude repeats as well as pseudogenes and, remarkably, a large sequence homology to the opposite breakpoint. In contrast, evolutionary inversion breakpoints lack such extensive cross-hybridizing regions and are often associated with fragile sites of the genome and low-copy repeats. These molecular characteristics gave evidence for different types of inversion formation and indicate that evolutionary inversions cannot originate from constitutional inversions like those of chromosomes 2 and 9. Finally, the constitutional inversion breakpoints were investigated on three different great ape species and on four test persons each bearing the same cytogenetically determined inversion on chromosomes 2 and 9, respectively. Our data indicate the existence of different molecular breakpoints for the two variant chromosomes.     

High-resolution array-CGH profiling of germline and tumor-specific copy number alterations on chromosome 22 in patients affected with schwannomas

Schwannomas may develop sporadically or in association with NF2 and schwannomatosis. The fundamental aberration in schwannomas is the bi-allelic inactivation of the NF2 gene. However, clinical and molecular data suggest that these tumors share a common pathogenetic mechanism related to as yet undefined 22q-loci. Linkage studies in schwannomatosis, a condition related to NF2, have defined a candidate 22q-locus and excluded the NF2 gene as the causative germline mutation. Thus, analysis of aberrations in schwannomas may lead to the identification of putative gene(s) involved in the development of schwannoma/schwannomatosis. We profiled a series of 88 schwannomas and constitutional DNA using a tiling path chromosome 22 array. Array-CGH is a suitable method for high-resolution discrimination between germline and tumor-specific aberrations. Previously reported frequencies of 22q-associated deletions in schwannomas display large discrepancies, ranging from 30% to 80%. We detected heterozygous deletions in 53% of schwannomas and the predominant pattern was monosomy 22. In addition, three tumors displayed terminal deletions and four harbored overlapping interstitial deletions of various sizes encompassing the NF2 gene. When profiling constitutional DNA, we identified eight loci that were affected by copy number variation (CNV). Some of the identified CNVs may not be phenotypically neutral and the possible role of these CNVs in the pathogenesis of schwannomas should be studied further. We observed a correlation between the breakpoint position, present in tumor and/or constitutional DNA and the location of segmental duplications. This association implicates these unstable regions in rearrangements occurring both in meiosis and mitosis.     

Constitutional Faith Law and Hope in Revolutionary Kyrgyzstan

This article investigates the interrelation between law and hope in the context of constitutional change in the Central Asian country of Kyrgyzstan. Drawing upon ethnographic and textual data, it is shown that the constitution has acquired particular discursive importance in Kyrgyzstan each time the foundations of the state have been severely challenged or shattered. Paying particular attention to three major political conflicts, the article demonstrates how, in the aftermath of each, speeches, performances, presentations and conversations were infused with ‘constitutional faith’, binding together the political elite and ordinary citizens in an expression of their general hope that constitutional change could bring about a better future. I view constitutional faith as a practice of hope that allows people to actively engage with their being-in-the-world, particularly in times of crisis. In the aftermath of large-scale political conflict, with which I am concerned here, it can become a faith-based mode of conflict resolution.     

Breakpoint mapping and haplotype analysis of three reciprocal translocations identify a novel recurrent translocation in two unrelated families: t(4;11)(p16.2;p15.4)

The majority of constitutional reciprocal translocations appear to be unique rearrangements arising from independent events. However, a small number of translocations are recurrent, most significantly the t(11;22)(q23;q11). Among large series of translocations there may be multiple independently ascertained cases with the same cytogenetic breakpoints. Some of these could represent additional recurrent rearrangements, alternatively they could be identical by descent (IBD) or have subtly different breakpoints when examined under higher resolution. We have used molecular breakpoint mapping and haplotyping to determine the origin of three pairs of reciprocal constitutional translocations, each with the same cytogenetic breakpoints. FISH mapping showed one pair to have different breakpoints and thus to be distinct rearrangements. Another pair of translocations were IBD with identical breakpoint intervals and highly conserved haplotypes on the derived chromosomes. The third pair, t(4;11)(p16.2;p15.4), had the same breakpoint intervals by aCGH and fosmid mapping but had very different haplotypes, therefore they represent a novel recurrent translocation. Unlike the t(11;22)(q23;q11), the formation of the t(4;11)(p16.2;p15.4) may have involved segmental duplications and sequence homology at the breakpoints. Additional examples of recurrent translocations could be identified if the resources were available to study more translocations using the approaches described here. However, like the t(4;11)(p16.2;p15.4), such translocations are likely to be rare with the t(11;22) remaining the only common recurrent constitutional reciprocal translocation.     

Redrawing the boundary of medical expertise: medically assisted reproduction and the debate on Italian bioconstitutionalism

In 2004, the Italian Parliament passed a controversial law on medically assisted reproduction (Law 40/2004). The Law obliged clinicians to create a maximum of three embryos during one in vitro fertilization (IVF) cycle and transfer them simultaneously into the patient’s uterus. With this “three embryo” standard, the Parliament sought to secure the realization of rights of IVF embryos. Drawing on the concepts of boundary-work [Gieryn, T. F. 1983. “Boundary-Work and the Demarcation of Science from Non-Science: Strains and Interests in Professional Ideologies of Scientists.” American Sociological Review 48 (6): 781–795] and bioconstitutionalism [Jasanoff, S., ed. 2011. Reframing Rights: Bioconstitutionalism in the Genetic Age. Cambridge, MA: MIT Press.], this article explores the role that the constitutional obligations of the Italian State towards its citizens, including IVF embryos as its new “citizen subjects,” played in how it envisaged and demarcated the professional boundaries of medical expertise. It argues that the latter depended upon how it balanced its commitments to protect the rights of IVF embryos and those of adult citizens. As such, the demarcation of the jurisdictional boundaries of medical expertise, and the definition of constitutional rights, formed two sides of the same governing project.     

Sensitivity of multiple color spectral karyotyping in detecting small interchromosomal rearrangements

Multiple color spectral karyotyping (SKY) has been proven to be a very useful tool for characterization of the complex rearrangements in cancer cells and the de novo constitutional structural abnormalities. The sensitivity of SKY in detecting interchromosomal alterations was assessed with 10 constitutional translocations involving subtelomeric regions. Among the 13 small segments tested, 9 were clearly visualized and 8 were unambiguously identified by SKY. Fluorescence in situ hybridizations (FISH) with subtelomeric probes confirmed the reciprocity in three of the four translocations in which a small segment was not detectable by SKY. On the basis of resolution level of G-banding and the information obtained from the FISH analysis, the minimum alteration that SKY can detect is estimated to be 1,000-2,000 kbp in size with the currently available probes. This study has demonstrated the power, but also the limitations, of SKY in detecting small interchromosomal alterations, particularly those in subtelomeric regions.     

Comparative mapping of the constitutional and tumor-associated 11;22 translocations.

The reciprocal t(11;22)(q23;q11) is the most common non-Robertsonian constitutional translocation in humans. The tumor-associated 11;22 rearrangement of Ewing sarcoma (ES) and peripheral neuroepithelioma (NE) is cytologically very similar to the 11;22 constitutional rearrangement. Using immunoglobulin light-chain constant region, ETS1 probes, and the technique of in situ hybridization, we previously were able to show that the constitutional and ES/NE breakpoints are different. As a first step toward isolating these translocation junctions and to further distinguish between them, we have made somatic cell hybrids. Cells from a constitutional 46,XX,inv(9),t(11;22) carrier and from an ES cell line with a t(11;22) were separately fused to a hypoxanthine-guanine phosphoribosyltransferase-deficient Chinese hamster cell line (RJK88). Resulting clones were screened with G-banding and Southern hybridization. Hybrid clones derived from the constitutional t(11;22) were established which contained the der(22) and both the der(22) and the der(11). Hybrid clones derived from the ES cell line containing the der(11) were isolated. Using the technique of Southern hybridization we have sublocalized the loci; ApoA1/C3, CD3D, ETS1, PBGD, THY1, D11S29, D11S34, and D11S147 to the region between the two breakpoints on chromosome 11 and V lambda I, V lambda VI, V lambda VII, and D22S10 to the region between the breakpoints on chromosome 22. Using anonymous DNA probes, we found that D22S9 and D22S24 map proximal to the constitutional breakpoint and that D22S15 and D22S32 map distal to the ES breakpoint on chromosome 22.     

Configurational analysis by residual dipolar couplings: A critical assessment of diastereomeric differentiabilities

Two independent statistical models for evaluating the certainties of configurational assignments of compounds based on nuclear magnetic resonance (NMR) data are evaluated and compared. Both methods yield weights or probabilities with which two or more structure models (constitutional or configurational isomers or even conformers) could be differentiated based on experimental parameters. Although this paper focusses on the use of residual dipolar couplings (RDCs) for the differentiation of diastereomers, the concept can be expanded to any set of experimental NMR‐derived parameters. It is demonstrated that highly reliable configurational assignments crucially must depend on thorough statistical analysis, which is frequently neglected in the literature.     

Hereditary multiple exostosis and chondrosarcoma: linkage to chromosome II and loss of heterozygosity for EXT-linked markers on chromosomes II and 8.

Hereditary multiple exostosis (EXT) is an autosomal dominant disorder characterized by bony exostoses at the ends of the long bones. Linkage studies have recently suggested that there are three chromosomal locations for EXT genes, 8q24.1 (EXT1), the pericentric region of 11 (EXT2), and 19p (EXT3). As part of a larger study to determine the frequencies of the three EXT types in the United States, we have ascertained a large multigenerational family with EXT and one family member with a chondrosarcoma. This family demonstrated linkage of the disease to chromosome 11 markers. The constitutional and tumor DNAs from the affected family member were compared using short-tandem-repeat markers from chromosomes 8, 11, and 19. Loss of heterozygosity (LOH) in the tumor was observed for chromosome 8 and 11 markers, but chromosome 19 markers were intact. An apparent deletion of the marker D11S903 was observed in constitutional DNA from all affected individuals and in the tumor sample. These results indicate that the EXT2 gene maps to the region containing marker D11S903, which is flanked by markers D11S1355 and D11S1361. Additional constitutional and chondrosarcoma DNA pairs from six unrelated individuals, two of whom had EXT, were similarly analyzed. One tumor from an individual with EXT demonstrated LOH for chromosome 8 markers, and a person with a sporadic chondrosarcoma was found to have tumor-specific LOH and a homozygous deletion of chromosome 11 markers. These findings suggest that EXT genes may be tumor-suppressor genes and that the initiation of tumor development may follow a multistep model.     

继代培养的玉米花粉胚性细胞系的倍性及其染色体上组成异染色质变异

来源于八趟白的细胞系No.1,经过六年半继代培养,显示出随着继代培养时间的延长,染色体数目变异的频率减低,其单倍性愈趋稳定。尽管继代培养时间的延长并不影响这个细胞系倍性的稳定性,但却能引起单倍体细胞中第4和第9染色体上的组成异染色质发生显著变异。     

Physiological responses of plants to heavy metals and the quantification of tolerance and toxicity

Abstract

Techniques available for assessing the tolerance of plants to heavy metal toxins are reviewed. All are based on physiological responses and range from long-term growth trials in metal-contaminated substrates, to rapid cytological tests. Problems associated with the ecophysiological interpretation of in vitro measurements of tolerance are considered. The implications of multiple tolerance, co-tolerance, constitutional tolerance, inducible tolerance and possible stimulatory effects of metals on plant responses are discussed.     

Legalization of Eco-balances in Germany

The development and use of, as well as scientific discussions on, eco-balances and in particular life cycle assessment has largely occurred without involving experts on environmental law. However, in the light of recent proposals to ‘legalize’ eco-balances, i.e. formally introducing them into environmental law, the legal implications of eco-balancing must be addressed in the future. The formal introduction, especially of LCA, cannot be decided independent of the general economic and environmental policy implications of material flow management, and it raises major questions of policy and constitutional law. An important question of principle is whether eco-balances should be prescribed or only a legal framework set forth for voluntary use. In view of the unfinished methodological development of LCA, any formal introduction raises the constitutional problem of conformity with the requirements of legal certainty. References to the ‘principles of good eco-balancing’ are problematic, and an introduction on an experimental basis would have to be confined to cases where the legal consequences of grossly divergent interpretations of this term are tolerable to affected firms. Where eco-balances are prescribed as a method of preparing governmental or administrative decisions, one must determine whether and to what extent they are binding on the decision-maker, and develop proper mechanisms of participation, transparency and critical review.     

Rapid isolation of moderate and highly polymorphic DNA fragments mapping close to WT (Wilms' tumour) and AN2 (aniridia) on chromosome 11

Summary Genes implicated in the development of Wilms' tumour (WT) and aniridia (AN2) have been localised to a subregion of band p13 on chromosome 11 by molecular and cytogenetic characterisation of WAGR syndrome patients carrying variable constitutional deletions. Polymorphic markers for the region would be valuable for linkage analysis in the familial forms of both Wilms' tumour and aniridia, as well as for studying somatic rearrangements of chromosome 11 in a variety of tumour types. Here we describe the isolation and characterisation of three frequently polymorphic arbitrary DNA fragments that map proximal to the AN2 and WT loci.     

A cryomicroscope for the analysis of solute polarization during freezing

A better understanding of the freezing process in the extracellular suspension medium implies the consideration of deviations from equilibrium, i.e., unsteady diffusion of heat and mass with a moving phase boundary. Such phenomena, especially solute redistribution in front of the advancing phase interface, can readily be investigated with a special cryomicroscope equipped with a spectrophotometer. A major advantage of this method is the combination of quantitative measurements in conjunction with visual observations, allowing a control of the solid-liquid interface morphology (planar-cellular-dendritic) which is crucial to the solidification process. The freezing stage designed for this purpose produces a temperature field in the sample layer resembling that within a large plate-shaped container, and hence well-defined thermal gradients (having a dominant effect on the shape of the interface). Aqueous solutions of NaMnO₄, exhibiting a maximum absorption at 525 nm and a phase diagram as well as diffusive properties very similar to NaCl in water, turned out to be a particularly suitable model for simulating of solidification of biological solutions. As long as freezing is unidimensional (planar), the concentration profiles can be scanned on-line, while multidimensional (cellular, dendritic) structures require off-line densitometric determination from photomicrographs. The experimental results agree quite well with mathematical models for both types of solidification. The observed transition points between planar freezing and higher-order structures correspond to those resulting from constitutional supercooling, a criterion roughly indicating the conditions for interface instability based on temperature and concentration gradients at the phase boundary.