Cytological analysis of the effect of treatments visualizing the chromosome core on non-histone nuclear proteins

A silver-stainable chromatid core is visualized under the light microscope on human leukocyte chromosomes by treating fixed chromosomes with 2M NaCl.An aminoacid which is not part of histone composition, 3H-tryptophan, is used to label the synthesis and location of non-histone proteins and to study the effect on these proteins of treatment with 2M NaCl and 0.2N HCl to visualize the core. 2M NaCl is shown to remove from nuclei and chromosomes an appreciable fraction of acid proteins, as well as all those synthesized during the two hours preceding the metaphase. 3H-Try labelling seems to preferentially affect only one chromatid per chromosome. The silver-stainable halocs appearing around numerous nuclei after treatment with 2M NaCl and 0.2N HCl are found to be labelled by 3H-Try and not by 3H-TdR.     

High T cell epitope sharing between two HLA-B27 subtypes (B*2705 and B*2709) differentially associated to ankylosing spondylitis.

HLA-B*2705 is strongly associated with ankylosing spondylitis (AS) and reactive arthritis. In contrast, B*2709 has been reported to be more weakly or not associated to AS. These two molecules differ by a single amino acid change: aspartic acid in B*2705 or histidine in B*2709 at position 116. In this study, we analyzed the degree of T cell epitope sharing between the two subtypes. Ten allospecific T cell clones raised against B*2705, 10 clones raised against B*2703 but cross-reactive with B*2705, and 10 clones raised against B*2709 were examined for their capacity to lyse B*2705 and B*2709 target cells. The anti-B*2705 and anti-B*2703 CTL were peptide dependent as demonstrated by their failure to lyse TAP-deficient B*2705-T2 transfectant cells. Eight of the anti-B*2705 and five of the anti-B*2703 CTL clones lysed B*2709 targets. The degree of cross-reaction between B*2705 and B*2709 was donor dependent. In addition, the effect of the B*2709 mutation (D116H) on allorecognition was smaller than the effect of the other naturally occurring subtype change at this position, D116Y. These results demonstrate that B*2705 and B*2709 are the antigenically closest HLA-B27 subtypes. Because allospecific T cell recognition is peptide dependent, our results imply that the B*2705- and B*2709-bound peptide repertoires are largely overlapping. Thus, to the extent to which linkage of HLA-B27 with AS is related to the peptide-presenting properties of this molecule, our results would imply that peptides within a relatively small fraction of the HLA-B27-bound peptide repertoire influence susceptibility to this disease.     

Cytometric evidence of cytogenetic and proliferative heterogeneity of human solid tumors

Flow cytometry is a widely recognized method of rapidly assessing the ploidy and proliferation status of experimental and solid tumors. In the present work, a variety of human cancers from various sites (lung, head and neck, etc.), of traditional interest in our laboratory, have been analyzed. In agreement with a number of recent reports, a general heterogeneity of human solid tumors can be evidenced. In particular: (a) solid tumors are characterized by a variable degree of aneuploidy; (b) the internal structure of solid tumors is highly heterogeneous especially with respect to the fraction of aneuploid malignant cells and their distribution through the cycle phases; and (c) some solid tumors are also characterized by the presence, to a variable extent, in the tumor of mass of multiple cell clones. Static fluorimetry of Feulgen-stained (mitotic) single cells offers a way to confirm this kind of observations.     

ACP1 and human adaptability 2. Association with season of conception

We have studied the pattern of association between the season of conception and cytosolic low molecular weight phosphotyrosine phosphatase (ACP1) genetic polymorphism in 329 consecutively newborn infants from the population of Penne and 361 consecutively newborn infants from the population of Rome. In addition, 329 mothers were studied in the population of Penne. A concordant, highly significant association was observed in the two populations between ACP1 parameters and the season of conception of newborn infants. The total activity of ACP1 shows a minimum in infants conceived in January–February and a maximum in those conceived at the end of the solar year. Analysis of the joint mother-newborn ACP1 distribution in relation to the season of fertilisation has shown that among mothers carrying ACP1*A (the allele showing the lowest activity), the proportion of newborns carrying this allele is higher in those conceived in the first months of the year than in those conceived subsequently. Since ACP1 probably functions as a phosphotyrosine phosphatase and as a flavin mononucleotide phosphatase, low activity could enhance the metabolic rate and would be advantageous in a cold environment. The cycle of variation of ACP1 in infants follows the cycle of solar illumination. It is possible that individuals who have a genetic background allowing them to adapt easily and readily to seasonal demand are more successful in reproducing themselves. The population of zygotes conceived in a given season would therefore reproduce the pattern of gene combination more fit for that season. Received: 15 June 1997 / Accepted: 31 July 1997     

Binding Thermodynamics of the Transition State Analogue Coformycin and of the Ground State Analogue 1-Deazaadenosine to Bovine Adenosine Deaminase

Binding of the transition state analogue coformycin and the ground state analogue 1-deaazadenosine to bovine adenosine deaminase have been thermody-namically characterized. The heat capacity changes for coformycin and 1-deazaadenosine binding are - 4.7 × 0.8 kJ/mole-K and -1.2 × 0.1 kJ/mole-K, respectively. Since the predominant source of heat capacity change in enzyme interactions are changes in the extent of exposure of nonpolar amino acid side chains to the aqueous environment and the hydrophobic effect is the predominant factor in native structure stabilization, we propose that the binding of either class of ligand is associated with a stabilizing enzyme conformational change with coformycin producing the far greater effect Analysis of the T dependence of the second order rate constant for formation of the enzyme/coformycin complex further reveals that the conformational change is not rate limiting. We propose that the enzyme may facilitate catalysis via the formation of a stabilizing conformation at the reaction transition state.     

Inhibitory CD161 receptor identified in glioma-infiltrating T cells by single-cell analysis

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Influence of ancient glacial periods on the Andean fauna: the case of the pampas cat (Leopardus colocolo)

Background  

While numerous studies revealed the major role of environmental changes of the Quaternary on the evolution of biodiversity, research on the influence of that period on current South-American fauna is scarce and have usually focused on lowland regions. In this study, the genetic structure of the pampas cat (Leopardus colocolo), a widely distributed felid, was determined and linked to ancient climate fluctuations on the Andean region.