Some dermatoglyphic traits in breast carcinoma

The finger and palmar prints of 60 women with breast carcinoma were studied. The results were compared with two groups of healthy women, the first consisted of old women and the second of young women. The dermatoglyphics seem to be of little use in the diagnosis of cancers of ectodermic origin. Supported by M.P.I. 60%, 1983     

Application of the Red List Index as an indicator of habitat change

For the first time ever, the International Union for Conservation of Nature Red List Index for habitat types was calculated for an entire country, Finland. The RLIs were based on species threat assessments from 2000 and 2010 and included habitat definitions for all 10,131 species of 12 organism groups. The RLIs were bootstrapped to track statistically significant changes. The RLI changes of species grouped by habitats were negative for all habitat types except for forests and rural biotopes which showed a stable trend. Trends of beetles and true bugs were positive in rural and forest habitats. Other 16 observed trends of species group and habitat combinations were negative. Several trends observed were in accordance with studies focusing on particular taxa and habitats, and drivers for their change. This study demonstrates the usefulness of the RLI as a tool for observing habitat change based on species threat assessment data.     

Population cytogenetics of aphidicolin-induced fragile sites

Summary Chromosome fragile sites are inducible by aphidicolin in cultured human lymphocytes. To assess the frequency and distribution of these common fragile sites in the general population, a cytogenetic survey was performed on 126 subjects, 59 males and 67 females, whose age ranged from 1 day to 72 years. Common fragile sites, induced by aphidicolin, were widespread and showed a remarkably different sensitivity among individuals; age influenced the overall frequency of fragile sites. Moreover, both age and sex seemed to modulate the expression of specific fragile sites. In our population, the most common fragile sites were: 3p14, 16q23, Xp22, 6q26, 1p31, 4q31, 1p22, 7q22, 2q33, 3q27, 2q31, 7q32, 14q24, 10q22, 5q31, 2q37, 6p21.     

A chicken beta-actin gene can complement a disruption of the Saccharomyces cerevisiae ACT1 gene.

Recently it was demonstrated that beta-actin can be produced in Saccharomyces cerevisiae by using the expression plasmid pY beta actin (R. Karlsson, Gene 68:249-258, 1988), and several site-specific mutants are now being produced in a protein engineering study. To establish a system with which recombinant actin mutants can be tested in vivo and thus enable a correlation to be made with functional effects observed in vitro, a yeast strain lacking endogenous yeast actin and expressing exclusively beta-actin was constructed. This strain is viable but has an altered morphology and a slow-growth phenotype and is temperature sensitive to the point of lethality at 37 degrees C.     

Physiological effects of micropauses in isometric handgrip exercise

The physiological response to continuous and intermittent handgrip exercise was evaluated. Three experiments were performed until exhaustion at 25% of maximal voluntary contraction (MVC): experiment 1, continuous handgrip (CH) (n = 8); experiment 2, intermittent handgrip with 10-s rest pause every 3 min (IH) (n = 8); and experiment 3, as IH but with electrical stimulation (ES) of the forearm extensors in the pauses (IHES) (n = 4). Before, during, and after exercise, recordings were made of heart rate (HR), arterial blood pressure (BP), exercising forearm blood flow, and concentrations of potassium [K+] and lactate [La-] in venous blood from both arms. The electromyogram (EMG) of the exercising forearm extensors and perceived exertion were monitored during exercise. Before and up to 24 h after exercise, observations were made of MVC, of force response to electrical stimulation and of the EMG response to a 10-s test contraction (handgrip) at 25% of the initial MVC. Maximal endurance time (tlim) was significantly longer in IH (23.1 min) than in CH (16.2 min). The ES had no significant effect on tlim. During exercise, no significant differences were seen between CH and IH in blood flow, venous [K+] and [La-], or EMG response. The HR and BP increased at the same rate in CH and IH but, because of the longer duration of IH, the levels at exhaustion were higher in this protocol. The subjects reported less subjective fatigue in IH. During recovery, return to normal MVC was slower after CH (24 h) than after IH (4 h).(ABSTRACT TRUNCATED AT 250 WORDS)     

The effects of temperature and adrenergic agonists on cardiac myocytes of perch (Perca fluviatilis) in cell culture conditions

1. 1. Isolated cardiac myocytes of perch, Perca fluviatilis, were kept in culture conditions for 1–2 months at 12 or 22°C. In the culture most myocytes flattened, lost their spindle-shaped morphology, protruded pseudopod-like branches and many of them started visible contractions in 1–2 weeks and continued beating for several months. Myocytes did not divide in the sparse cell population used. Typical intracellular structures could be seen in electron micrographs still after 1–2 months, but the sarcoplasmic organization became gradually more irregular in the culture.

2. 2. Beat rates showed linear temperature relationship on the Arrhenius plot. Myocytes cultivated at 22°C showed higher frequencies and slightly less dependence on temperature than myocytes cultivated at 12°C (apparent activation energies (E_a) 86 and 107 kJ/mol, respectively).

3. 3. Temperature dependence of frequencies was related to the presence of added serum or adrenergic agonists: β-adrenergic agonists increased the frequencies and rendered the cells less dependent on temperature; apparent activation energy was 43 kJ/mol for isoprenaline or adrenaline and 108 kJ/mol for noradrenaline and control group.

4. 4. Heat tolerance was greater in myocytes cultivated at 22°C than in myocytes cultivated at 12°C, and the change in tolerance appeared in 12 h after the alteration of culture temperature and the increased tolerance was persistent after that.

5. 5. It is suggested, that the processes of quick heat-hardening and of slower but persistent heat resistance acclimation developed in these cells in culture conditions but not the capacity acclimation, which seems to be dependent on adrenergic regulation of beat rate.

Mutations in the chemotactic response regulator, CheY, that confer resistance to the phosphatase activity of CheZ

CheY, a small cytoplasmic response regulator, plays an essential role in the chemotaxis pathway. The concentration of phospho-CheY is thought to determine the swimming behaviour of the cell: high levels of phospho-CheY cause bacteria to rotate their flagella clockwise and tumble, whereas low levels of the phos-phorylated form of the protein allow counter-ciockwise rotation of the flagella and smooth swimming. The phosphorylation state of CheY in vivo is determined by the activity of the phosphoryl donor CheA, and by the antagonistic effect of dephosphorylation of phospho-CheY. The dephosphorylation rate is controlled by the intrinsic autohydrolytic activity of phospho-CheY and by the CheZ protein, which accelerates dephosphorylation. We have analysed the effect of CheZ on the dephosphorylation rates of several mutant CheY proteins. Two point mutations were identified which were 50-fold and 5-fold less sensitive to the activity of CheZ than was the wild-type protein. Nonetheless, the phosphorylation and autodephos-phorylation rates of these mutants, CheY23ND and CheY26KE, were observed to be identical to those of wild-type CheY in the absence of CheZ. These are the first examples of CheY mutations that reduce sensitivity to the phosphatase activity of CheZ without being altered in terms of their intrinsic phosphorylation and autodephospborylation rates, interestingly, the residues Asn-23 and Lys-26 are located on a face of CheY far from the phosphorylation site (Asp-57), distinct from the previously described site of inter-action with the histidine kinase CheA, and partially overlapping with a region implicated in interaction with the flagellar switch.     

Design,synthesis, and biological screening of a series of 4′-fluoro-benzotriazole-acrylonitrile derivatives as microtubule-destabilising agents (MDAs)

Introduction: Colchicine-binding site inhibitors are some of the most interesting ligands belonging to the wider family of microtubule-destabilising agents.Results: A novel series of 4′-fluoro-substituted ligands (5–13) was synthesised. The antiproliferative activity assays resulted in nM values for the new benzotriazole-acrylonitrile derivatives. Compound 5, the hit compound, showed an evident blockade of HeLa cell cycle in the G2-M phase, but also a pro-apoptotic potential, and an increase of early and late apoptotic cells in HeLa and MCF-7 cell cycle analysis. Confocal microscopy analysis showed a segmented shape and a collapse of the cytoskeleton, as well as a consistent cell shrinkage after administration of 5 at 100 nM. Derivative 5 was also proved to compete with colchicine at colchicine-binding site, lowering its activity against tubulin polymerisation. In addition, co-administration of 5 and doxorubicin in drug-resistant A375 melanoma cell line highlighted a synergic potential in terms of inhibition of cell viability.Discussion: The 4′-fluoro substitution of benzotriazole-acrylonitrile scaffold brought us a step forward in the optimisation process to obtain compound 5 as promising MDA antiproliferative agent at nanomolar concentration.