Antitumor Effects of 3,3′,4,4′,5,5′-Hexahydroxystilbene in hl-60 Human Promyelocytic Leukemia Cells

Resveratrol (3,4′,5-trihydroxystilbene, RV) exerts remarkable cytostatic and cytotoxic effects against a multitude of human cancer cell lines. Since the introduction of additional hydroxyl groups was supposed to increase the biological activity of RV, we have synthesized a number of polyhydroxylated stilbene analogues as potential antitumor agents. In this study, the activity of 3,3′,4,4′,5,5′-hexahydroxystilbene (M8) was investigated in HL-60 human promyelocytic leukemia cells. Employing a growth inhibition assay, incubation with M8 and RV resulted in IC₅₀ values of 6.25 and 12 μM, respectively. Using a specific Hoechst/propidium iodide double staining method, we found that M8 was able to induce apoptosis in concentrations significantly lower than those of RV. In addition, M8 arrested cells in the S phase and totally depleted cells in the G2-M phase of the cell cycle (143% and 0% of control after treatment with 12.5 μM M8, respectively). We therefore believe that this promising agent deserves further preclinical and in vivo testing.     

Investigating structure and temporal scale in social organizations using identified individuals

Studies of individually identified animals can produce substantialdata sets containing information on the structure and temporalscale of social organizations. However, methods of analyzingsuch data are not well established. Important features of asocial organization are revealed by plotting the rate of persistenceof the associations between pairs of individuals over a rangeof time lags (lagged association rate). The consistency of long-termrelationships can be characterized using the rate of associationof pairs of individuals between their first and last observedassociations (intermediate association rate). A hierarchicalseries of models featuring exponentially decaying lagged associationrates may be fitted to these data. This technique retrievedthe essential parameters of five simulated social organizationsand, when used on real data, portrayed the essential featuresof the patterns of temporal change in relationships betweenanimals. The method should be especially useful for analyzingfissionfusion societies containing 10–10, 000 individuallyidentifiable animals.     

Principles and pitfalls in designing site-directed peptide ligands

An immunoglobulin light chain dimer with a large generic binding cavity was used as a host molecule for designing a series of peptide guest ligands. In a screening procedure peptides coupled to solid supports were systematically tested for binding activity by enzyme linked immunosorbent assays (ELISA). Key members of the binding series were synthesized in milligram quantities and diffused into crystals of the host molecule for X-ray analyses. These peptides were incrementally increased in size and affinity until they nearly filled the cavity. Progressive changes in binding patterns were mapped by comparisons of crystallo-graphically refined structures of 14 peptide–protein complexes at 2.7 Å resolution. These comparisons led to guidelines for ligand design and also suggested ways to modify previously established binding patterns. By manipulating equilibria involving histidine, for example, it was possible to abolish one important intramolecular interaction of the bound ligand and substitute another. These events triggered a change inconformation of the ligand from a compact to an extended form and a comprehensive change in the mode of binding to the protein. In dipeptides of histidine and proline, protonation of both imidazolium nitrogen atoms was used to program anend-to-end reversal of the direction in which the ligand was inserted into the binding cavity. Peptides cocrystallized with proteins produced complexes somewhat different in structure from those in which ligandswere diffused into preexisting crystals. In sucha large and malleable cavity, space utilization was thus different when a ligand was introduced before the imposition of crystal packing restraints. © 1993 Wiley-Liss, Inc.     

A HEMATOLOGICAL STUDY IN MICE FOR EVALUATION OF LEUKEMOGENESIS BY EXTREMELY LOW FREQUENCY MAGNETIC FIELDS

OF1 mice were chronically exposed to a 50-Hz sinusoidal East–West magnetic field of 15 μT (rms), in order to make a peripheral blood study for a leukemogenic evaluation of this non-ionizing radiation. Mating and pregnancy of ancestors (first generation), and birth, lactation, and development of second-generation female mice until adulthood occurred in the experimental field. A hematological study of both control and exposed 14- to 15-week-old and 50- to 52-week-old, second-generation females was realized. Individual diagnosis of specimens and statistical analysis of results revealed a high incidence of blood leukoproliferative disorders in 14- to 15-week-old exposed females (relative risk [RR] = 3.00, p = 0.0033), despite the resistance of this strain of mice to developing malignancies under normal environmental conditions before they are 26 weeks old. Especially elevated incidences of lymphocytic (RR = 6.50, p = 0.0021) and chronic (RR = 4.00, p = 0.0153) leukemias were associated with medium-term (14–15 weeks) exposure. After 50–52 weeks of exposure, the mortality of exposed mice was 30% versus 0% of control mice. From dead exposed females, 67% revealed some type of malignancy. Corresponding RR for blood leukoproliferative disorders of those exposed which survived was 2.57 (p = 0.0351). Especially important was the proportion of chronic leukemias after long-term (50–52 weeks) exposure (RR = 8.57, p = 0.0118). Moreover, a statistically nonsignificant increase of lymphoblastic–myeloblastic leukemias pointed to a relation between age of specimen and type of alteration. We suggest that the increase in blood leukemias in OF1 mice agrees with the results of numerous epidemiological studies.     

Bisphenol A and Risk Management Ethics

It is widely recognized that endocrine disrupting compounds, such as Bisphenol A, pose challenges for traditional paradigms in toxicology, insofar as these substances appear to have a wider range of low‐dose effects than previously recognized. These compounds also pose challenges for ethics and policymaking. When a chemical does not have significant low‐dose effects, regulators can allow it to be introduced into commerce or the environment, provided that procedures and rules are in place to keep exposures below an acceptable level. This option allows society to maximize the benefits from the use of the chemical while minimizing risks to human health or the environment, and it represents a compromise between competing values. When it is not possible to establish acceptable exposure levels for chemicals that pose significant health or environmental risks, the most reasonable options for risk management may be to enact either partial or complete bans on their use. These options create greater moral conflict than other risk management strategies, leaving policymakers difficult choices between competing values.     

Experimentally induced helper dispersal in colonially breeding cooperative cichlids

The ‘benefits of philopatry’ hypothesis states that helpers in cooperatively breeding species derive higher benefits from remaining home, instead of dispersing and attempting to breed independently. We tested experimentally whether dispersal options influence dispersal propensity in the cooperatively breeding Lake Tanganyika cichlids Neolamprologus pulcher and N. savoryi. Cooperative groups of these fishes breed in densely packed colonies, surrounded by unoccupied, but apparently suitable breeding habitat. Breeding inside colonies and living in groups seems to benefit individuals, for example by early detection and deterrence of predators. We show that despite a slight preference of both species for habitat with a higher stone cover, 40% of the preferred habitat remained unoccupied. On average, the colonies contained a higher number of (1) predators of adults, juveniles and eggs, (2) shelter competitors, and (3) other species including potential food competitors, compared to the outside colony habitat. Apparently, habitat differences cannot explain why these cichlids breed in colonies. Accordingly, dispersal may not be limited by a lack of suitable breeding shelters, but by the relatively higher risk of establishing an outside- compared to a within-colony breeding territory. To test whether cichlids prefer within- to outside-colony breeding territories, we provided breeding shelters inside the colony and at the colony edge and studied helper dispersal. As expected, significantly more shelters were occupied within the colony compared to the edge. New breeding pairs with several helpers occupied these shelters. We conclude that although breeding habitat is plentiful outside the colonies, helpers delay dispersal to obtain a higher quality breeding position within the group or colony eventually, or they disperse in groups. Our results suggest that (1) group augmentation and Allee effects are generally important for dispersal decisions in cooperatively breeding cichlids, consistent with the ‘benefits of philopatry hypothesis’, and (2) habitat saturation cannot fully explain delayed dispersal in these species.     

Scale effects and constraints for sound production in katydids (Orthoptera: Tettigoniidae): correlated evolution between morphology and signal parameters

Male katydids (Orthoptera: Tettigoniidae) produce mating calls by rubbing the wings together, using specialized structures in their forewings (stridulatory file, scraper and mirror). A large proportion of species (ca. 66%) reported in the literature produces ultrasonic signals as principal output. Relationships among body size, generator structures and the acoustic parameters carrier frequency (f_c) and pulse duration (p_d), were studied in 58 tropical species that use pure‐tone signals. A comparative analysis, based on the only available katydid phylogeny, shows how changes in sound generator form are related to changes in f_c and p_d. Anatomical changes of the sound generator that might have been selected via f_c and p_d are mirror size, file length and number of file teeth. Selection for structures of the stridulatory apparatus that enhance wing mechanics via file‐teeth and scraper morphology was crucial in the evolution of ultrasonic signals in the family Tettigoniidae.     

Linking dispersal, immigration and scale in the neutral theory of biodiversity

In the classic spatially implicit formulation of Hubbell's neutral theory of biodiversity a local community receives immigrants from a metacommunity operating on a relatively slow timescale, and dispersal into the local community is governed by an immigration parameter m . A current problem with neutral theory is that m lacks a clear biological interpretation. Here, we derive analytical expressions that relate the immigration parameter m to the geometry of the plot defining the local community and the parameters of a dispersal kernel. Our results facilitate more rigorous and extensive tests of the neutral theory: we conduct a test of neutral theory by comparing estimates of m derived from fits to empirical species abundance distributions to those derived from dispersal kernels and find acceptable correspondence; and we generate a new prediction of neutral theory by investigating how the shapes of species abundance distributions change theoretically as the spatial scale of observation changes. We also discuss how our main analytical results can be used to assess the error in the mean-field approximations associated with spatially implicit formulations of neutral theory.