CHROMOSOME NUMBERS IN COMPOSITAE V. ASTEREAE II.

Reports of 100 new chromosome counts are made for the tribe Astereae of Compositae, mostly based on determinations of meiotic material, including first counts for 9 genera and 53 species. Counts are now available for 58 of the approximately 100–120 genera and 431 of the approximately 2000 species in the tribe. Comparisons are made between chromosome number and habit and also between chromosome number and geographical distribution. Species and genera with a basic number of x = 9 are the most abundant. Within different phyletic lines x = 9 is also the most abundant number. On the other hand, many species with x = 4 and 5, belonging to a number of small, largely annual genera, are concentrated in southwestern North America. The low chromosome number in these plants is probably correlated with the dry habitat they occupy, and is most likely a specialized condition.     

The influence of partial androgen deficiency of aging men (PADAM) on the impulse regime of incretion of several hormones and mitotic activity

This research work is devoted to an important subject--study of the impulse regime of the incretion of a series of hormones among men with partial androgen deficience of aging men (PADAM). The results of this study suggest that PADAM leads to a breakdown of the impulse regime of incretion of a series of hormones, including luteinizing hormone (LH), follicle stimulating hormone (FSH), and somatotropic hormones (STH), as well as cortisol and insulin among men of older age groups. These changes accompany the development of metabolic syndrome (X-syndrome); their development can be inversed through androgen-replacement therapy.     

Range and variation in the genusCeratozamia (Zamiaceae)

The genusCeratozamia has an extensive distribution that starts in northeastern Mexico and continues southward and southeastward into Guatemala, Belize, and Honduras. Over this extensive distributional rangeCeratozamia is found in numerous disjunct populations. These populations are never very widespread and are often restricted to a single mountain or canyon. Because of the restricted range of these populations, and the lack of genetic exchange between them, many of them have evolved into easily identifiable groups. At the present time there are 16 validly published species ofCeratozamia, with several more possible new species under investigation.     

POPULATION DYNAMICS OF INTESTINAL EPITHELIA IN THE RAT TWO MONTHS AFTER PARTIAL RESECTION OF THE ILEUM

Sprague-Dawley rats that had been subjected 2 months previously to partial resection (10 per cent) of the small intestine and an equal number of control rats were injected with tritiated thymidine and sacrificed at intervals during the subsequent 16 hours. Segments of duodenum, jejunum and ileum were prestained by the Feulgen technique and radioautographed. The proportion of crypt cells bearing labeled nuclei, the percentage of labeled crypt cells in mitosis and the appearance of labeled crypt cells on the villi were determined. Comparison of control and resected rats showed that (a) the proportion of intestinal crypt cells incorporating thymidine was considerably greater and uniformly high throughout the shortened intestine, (b) the life cycle of crypt cells was slightly reduced, and was uniform throughout the shortened intestine, and (c) the time during which cells were retained in crypts was markedly reduced. On the basis of persistent, generalized increase in the production of crypt cells, and on prior evidence that the epithelial cells of shortened intestine continue to have a brief life span and evidence of metabolic immaturity, the existence of a humoral factor, tentatively called "intestinal epithelial growth hormone," is postulated.     

Cdc48Ufd1/Npl4 segregase removes mislocalized centromeric histone H3 variant CENP-A from non-centromeric chromatin

Restricting the localization of CENP-A (Cse4 in Saccharomyces cerevisiae) to centromeres prevents chromosomal instability (CIN). Mislocalization of overexpressed CENP-A to non-centromeric chromatin contributes to CIN in budding and fission yeasts, flies, and humans. Overexpression and mislocalization of CENP-A is observed in cancers and is associated with increased invasiveness. Mechanisms that remove mislocalized CENP-A and target it for degradation have not been defined. Here, we report that Cdc48 and its cofactors Ufd1 and Npl4 facilitate the removal of mislocalized Cse4 from non-centromeric chromatin. Defects in removal of mislocalized Cse4 contribute to lethality of overexpressed Cse4 in cdc48,ufd1 andnpl4 mutants. High levels of polyubiquitinated Cse4 and mislocalization of Cse4 are observed in cdc48-3, ufd1-2 and npl4-1mutants even under normal physiological conditions, thereby defining polyubiquitinated Cse4 as the substrate of the ubiquitin directed segregase Cdc48^Ufd1/Npl4. Accordingly, Npl4, the ubiquitin binding receptor, associates with mislocalized Cse4, and this interaction is dependent on Psh1-mediated polyubiquitination of Cse4. In summary, we provide the first evidence for a mechanism that facilitates the removal of polyubiquitinated and mislocalized Cse4 from non-centromeric chromatin. Given the conservation of Cdc48^Ufd1/Npl4 in humans, it is likely that defects in such pathways may contribute to CIN in human cancers.     

Assignments, secondary structure and dynamics of the inhibitor-free catalytic fragment of human fibroblast collagenase

Fibroblast collagenase (MMP-1), a 169-residue protein with amolecular mass of 18.7 kDa, is a matrix metalloproteinase which has beenassociated with pathologies such as arthritis and cancer. The assignments ofthe ¹H, ¹⁵N, ¹³CO and¹³C resonances, determination of the secondary structure andanalysis of ¹⁵N relaxation data of the inhibitor-freecatalytic fragment of recombinant human fibroblast collagenase (MMP-1) arepresented. It is shown that MMP-1 is composed of a -sheet consistingof five -strands in a mixed parallel and antiparallel arrangement(residues 13–19, 48–53, 59–65, 82–85 and94–99) and three -helices (residues 27–43, 112–124and 150–160). This is nearly identical to the secondary structuredetermined from the refined X-ray crystal structures of inhibited MMP-1. Themajor difference observed between the NMR solution structure ofinhibitor-free MMP-1 and the X-ray structures of inhibited MMP-1 is thedynamics of the active site. The 2D ¹⁵N-¹H HSQCspectra, the lack of information in the ¹⁵N-edited NOESYspectra, and the generalized order parameters (S²) determinedfrom ¹⁵N T₁, T₂ and NOE datasuggest a slow conformational exchange for residues comprising the activesite (helix B, zinc ligated histidines and the nearby loop region) and ahigh mobility for residues Pro¹³⁸-Gly¹⁴⁴ in thevicinity of the active site for inhibitor-free collagenase. In contrast tothe X-ray structures, only the slow conformational exchange is lost in thepresence of an inhibitor.     

Testosterone's role in regulating expression of genes of several proliferation factors

This research work focuses on an important topic--the study of cause and effect links between partial androgen deficiency of ageing men (PADAM) and an increased expression of genes of a series of factors that make proliferate activity. The results of this research show that an increased expression of genes of several proliferation factors, and a decreased expression of the gene of the insulin receptor among men of older age groups are all connected to PADAM. The given changes are directed at compensation for testicular inadequacy, and are a particular expression of metabolic syndrome (X-syndrome); their effect can be inversed however by androgen-replacement therapy.     

Reduced gene dosage of histone H4 prevents CENP-A mislocalization and chromosomal instability in Saccharomyces cerevisiae

Mislocalization of the centromeric histone H3 variant (Cse4 in budding yeast, CID in flies, CENP-A in humans) to noncentromeric regions contributes to chromosomal instability (CIN) in yeast, fly, and human cells. Overexpression and mislocalization of CENP-A have been observed in cancers, however, the mechanisms that facilitate the mislocalization of overexpressed CENP-A have not been fully explored. Defects in proteolysis of overexpressed Cse4 (GALCSE4) lead to its mislocalization and synthetic dosage lethality (SDL) in mutants for E3 ubiquitin ligases (Psh1, Slx5, SCF^Met30, and SCF^Cdc4), Doa1, Hir2, and Cdc7. In contrast, defects in sumoylation of overexpressed cse4K215/216/A/R prevent its mislocalization and do not cause SDL in a psh1Δ strain. Here, we used a genome-wide screen to identify factors that facilitate the mislocalization of overexpressed Cse4 by characterizing suppressors of the psh1Δ GALCSE4 SDL. Deletions of histone H4 alleles (HHF1 or HHF2), which were among the most prominent suppressors, also suppress slx5Δ, cdc4-1, doa1Δ, hir2Δ, and cdc7-4 GALCSE4 SDL. Reduced dosage of H4 leads to defects in sumoylation and reduced mislocalization of overexpressed Cse4, which contributes to suppression of CIN when Cse4 is overexpressed. We determined that the hhf1-20, cse4-102, and cse4-111 mutants, which are defective in the Cse4-H4 interaction, also exhibit reduced sumoylation of Cse4 and do not display psh1Δ GALCSE4 SDL. In summary, we have identified genes that contribute to the mislocalization of overexpressed Cse4 and defined a role for the gene dosage of H4 in facilitating Cse4 sumoylation and mislocalization to noncentromeric regions, leading to CIN when Cse4 is overexpressed.