Viviparous mothers impose stronger glucocorticoid‐mediated maternal stress effects on their offspring than oviparous mothers

Maternal stress during gestation has the potential to affect offspring development via changes in maternal physiology, such as increases in circulating levels of glucocorticoid hormones that are typical after exposure to a stressor. While the effects of elevated maternal glucocorticoids on offspring phenotype (i.e., “glucocorticoid‐mediated maternal effects”) have been relatively well established in laboratory studies, it remains poorly understood how strong and consistent such effects are in natural populations. Using a meta‐analysis of studies of wild mammals, birds, and reptiles, we investigate the evidence for effects of elevated maternal glucocorticoids on offspring phenotype and investigate key moderators that might influence the strength and direction of these effects. In particular, we investigate the potential importance of reproductive mode (viviparity vs. oviparity). We show that glucocorticoid‐mediated maternal effects are stronger, and likely more deleterious, in mammals and viviparous squamate reptiles compared with birds, turtles, and oviparous squamates. No other moderators (timing and type of manipulation, age at offspring measurement, or type of trait measured) were significant predictors of the strength or direction of the phenotypic effects on offspring. These results provide evidence that the evolution of a prolonged physiological association between embryo and mother sets the stage for maladaptive, or adaptive, prenatal stress effects in vertebrates driven by glucocorticoid elevation.     

Patch size drives colonization by aquatic insects,with minor priority effects of a cohabitant

Patch size is one of the most important factors affecting the distribution and abundance of species, and recent research has shown that patch size is an important niche dimension affecting community structure in aquatic insects. Building on this result, we examined the impact of patch size in conjunction with presence of larval anurans on colonization by aquatic insects. Hyla chrysoscelis (Cope''s gray treefrog) larvae are abundant and early colonists in fishless lentic habitats, and these larvae can fill multiple ecological roles. By establishing larvae in mesocosms prior to colonization, we were able to assess whether H. chrysoscelis larvae have priority effects on aquatic insect assemblages. We conducted a series of three experiments in naturally colonized experimental landscapes to test whether (1) H. chrysoscelis larval density affects insect colonization, (2) variation in patch size affects insect colonization, and (3) the presence and larval density of H. chrysoscelis shift colonization of insects between patches of different size. Larval density independently had almost no effect on colonization, while patch size had species‐specific effects consistent with prior work. When larvae and patch size were tested in conjunction, patch size had numerous, often strong, species‐specific effects on colonization; larval density had effects largely limited to the assemblages of colonizing beetles and water bugs, with few effects on individual species. Higher larval densities in large mesocosms shifted some insect colonization to smaller patches, resulting in higher beta diversity among small patches in proximity to high density large mesocosms. This indicates establishing H. chrysoscelis larvae prior to insect colonization can likely create priority effects that slightly shape insect communities. Our results support the importance of patch size in studying species abundances and distributions and also indicate that colonization order plays an important role in determining the communities found within habitat patches.     

Low-level exposure to radiofrequency electromagnetic fields: Health effects and research needs

The World Health Organization (WHO), the International Commission on Non-Ionizing Radiation Protection (ICNIRP), and the German and Austrian Governments jointly sponsored an international seminar in November of 1996 on the biological effects of low-level radiofrequency (RF) electromagnetic fields. For purposes of this seminar, RF fields having frequencies only in the range of about 10 MHz to 300 GHz were considered. This is one of a series of scientific review seminars held under the International Electromagnetic Field (EMF) Project to identify any health hazards from EMF exposure. The scientific literature was reviewed during the seminar and expert working groups formed to provide a status report on possible health effects from exposure to low-level RF fields and identify gaps in knowledge requiring more research to improve health risk assessments. It was concluded that, although hazards from exposure to high-level (thermal) RF fields were established, no known health hazards were associated with exposure to RF sources emitting fields too low to cause a significant temperature rise in tissue. Biological effects from low-level RF exposure were identified needing replication and further study. These included in vitro studies of cell kinetics and proliferation effects, effects on genes, signal transduction effects and alterations in membrane structure and function, and biophysical and biochemical mechanisms for RF field effects. In vivo studies should focus on the potential for cancer promotion, co-promotion and progression, as well as possible synergistic, genotoxic, immunological, and carcinogenic effects associated with chronic low-level RF exposure. Research is needed to determine whether low-level RF exposure causes DNA damage or influences central nervous system function, melatonin synthesis, permeability of the blood brain barrier (BBB), or reaction to neurotropic drugs. Reported RF-induced changes to eye structure and function should also be investigated. Epidemiological studies should investigate: the use of mobile telephones with hand-held antennae and incidence of various cancers; reports of headache, sleep disturbance, and other subjective effects that may arise from proximity to RF emitters, and laboratory studies should be conducted on people reporting these effects; cohorts with high occupational RF exposure for changes in cancer incidence; adverse pregnancy outcomes in various highly RF exposed occupational groups; and ocular pathologies in mobile telephone users and in highly RF exposed occupational groups. Studies of populations with residential exposure from point sources, such as broadcasting transmitters or mobile telephone base stations have caused widespread health concerns among the public, even though RF exposures are very low. Recent studies that may indicate an increased incidence of cancer in exposed populations should be investigated further. Bioelectromagnetics 19:1–19, 1998. © 1998 Wiley-Liss, Inc.     

Applied DC magnetic fields cause alterations in the time of cell divisions and developmental abnormalities in early sea urchin embryos

Most work on magnetic field effects focuses on AC fields. The present study demonstrates that exposure to medium-strength (10 mT-0.1 T) static magnetic fields can alter the early embryonic development of two species of sea urchin embryos. Batches of fertilized eggs from two species of urchin were exposed to fields produced by permanent magnets. Samples of the continuous cultures were scored for the timing of the first two cell divisions, time of hatching, and incidence of exogastrulation. It was found that static fields delay the onset of mitosis in both species by an amount dependent on the exposure timing relative to fertilization. The exposure time that caused the maximum effect differed between the two species. Thirty millitesla fields, but not 15 mT fields, caused an eightfold increase in the incidence of exogastrulation in Lytechinus pictus, whereas neither of these fields produced exogastrulation in Strongylocentrotus purpuratus. Bioelectromagnetics 18:255–263, 1997. © 1997 Wiley-Liss, Inc.     

Magnetic field effects on coenzyme B12-dependent enzymes: Validation of ethanolamine ammonia lyase results and extension to human methylmalonyl CoA mutase

Enzymes with radical-pair intermediates have been considered as a likely target for purported magnetic field effects in humans. The bacterial enzyme ethanolamine ammonia lyase and the human enzyme methylmalonyl-CoA mutase catalyze coenzyme B₁₂-dependent rearrangement reactions. A common step in the mechanism of these two enzymes is postulated to be homolysis of the cobalt-carbon bond of the cofactor to generate a spin-correlated radical pair consisting of the 5′-deoxyadenosyl radical and cob(II)alamin [Ado^· Cbl(II)]. Thus, the reactions catalyzed by these enzymes are expected to be sensitive to an applied magnetic field according to the same principles that control radical pair chemical reactions. The magnetic field effect on ethanolamine ammonia lyase reported previously has been corroborated independently in one of the authors' laboratory. However, neither the human nor the bacterial mutase from Propionibacterium shermanii exhibits a magnetic field effect that could be greater than about 15%, considering the error limit imposed by the uncertainty of the coupled assay. Our studies suggest that putative magnetic field effects on physiological processes are not likely to be mediated by methylmalonyl-CoA mutase. Bioelectromagnetics 18:506–513, 1997. © 1997 Wiley-Liss, Inc.     

The effect of ultrasound cavitation on endothelial cells

Acoustic cavitation has been widely explored for both diagnostic and therapeutic purposes. Ultrasound-induced cavitation, including inertial cavitation and non-inertial cavitation, can cause microstreaming, microjet, and free radical formation. The acoustic cavitation effects on endothelial cells have been studied for drug delivery, gene therapy, and cancer therapy. Studies have demonstrated that the ultrasound-induced cavitation effect can treat cancer, ischaemia, diabetes, and cardiovascular diseases. In this minireview, we will review the impact of ultrasound-induced cavitation on the endothelial cells such as cell permeability, cell proliferation, gene expression regulation, cell viability, hemostasis interaction, oxygenation, and variation in the level of calcium ions, ceramide, nitric oxide (NO) and nitric oxide synthase (NOS) activity. The applications of these effects and the cavitation mechanism involved will be summarized, demonstrating the important role of acoustic cavitation in non-invasive ultrasound treatment of various physiological conditions.     

Genetic variation in rural and urban populations of Epipactis helleborine (L.) Crantz. (Orchidaceae) in Britain

Genetic variation in Epipactis helleborine in the British Isles was assessed using starch gel electrophoresis of isozymes; 273 individuals were sampled from 13 populations and examined for genetic variation using eight enzyme systems encoded for by 13 loci. Overall, 46% of the loci examined were polymorphic, with an average of 1.69 alleles per locus. Within populations, a mean of 33% of the loci were polymorphic, with a mean number of 1.46 alleles per locus. Levels of genetic variation were compared between urban and well established rural populations to assess the genetic consequences of colonization of the urban sites. The average levels of genetic variation detected in urban populations were lower than that found in rural populations, although there was a much greater range of variation among the urban populations. Large urban populations actually have patterns of variation similar to rural populations and show evidence of multiple founders. This indicates that the high dispersibility of Epipactis seeds can in some cases overcome the predicted loss of genetic variation associated with founder effects during colonization. Small urban populations, however, show significantly lower levels of genetic variation compared with these large urban populations and the rural populations, and it seems likely that this is attributable to single founding events and/or genetic drift.     

Induction of CCK mRNA levels in the limbic-hypothalamic circuit: Time course and site-specific effects of estrogen

Estrogenic regulation of cholecystokinin (CCK) and its receptors is correlated with the initiation and termination of lordosis behavior. To understand the effect of circulating estrogen concentration on the temporal aspects of CCK mRNA expression in the posterodorsal medial amygdaloid nucleus (MeApd) and the central part of the medial preoptic nucleus (MPNc) of the limbic-hypothalamic circuit, ovariectomized female rats were treated with a 10 mm Silastic™ capsule filled with estradiol, a bolus injection of 50 μg estradiol benzoate or 2 μg estradiol benzoate every 4 days for five “cycles.” In situ hybridization was used to compare the relative changes of CCK mRNA levels at 0 h to levels measured at 6, 12, 24, 48, 72, or 96 h after estrogen administration. In the MPNc and the MeApd, the 10-mm capsule significantly increased and maintained CCK mRNA levels from 6 to 96 h. The range of the increase was 3.0–5.1-fold in the MPNc and 2.8–5.0 in the MeApd. The 50-μg injections significantly increased and maintained CCK mRNA levels in the MPNc from 12 to 96 h (range of the increase 2.4–4.1-fold) and in the MeApd from 24 to 96 h (range of the increase 2.2–2.8-fold). The repeated administration of 2 μg estrogen induced a significant increase of message levels in the MPNc at 12 and 24 h that were 4.2- and 4.7-fold, respectively. In the MeApd this estrogen treatment did not significantly increase CCK mRNA. These studies demonstrate that small doses (2 μg) of estrogen that mimic the pattern and circulating levels of estrogen dramatically stimulate CCK mRNA levels in the limbic-hypothalamic circuit. To further study this steroid stimulation, ovariectomized female rats were implanted with estradiol-filled cannulae into the bed nucleus of the stria terminalis or MeA. Estrogen elevated CCK mRNA levels locally in each nucleus. Implants in the bed nucleus also elevated CCK mRNA levels in the MeApd indicating that physiologic estrogen stimulation of CCK in the MeApd is the result of both local and distal transsynaptic elevation of CCK mRNA levels. The site-specific induction of CCK mRNA levels within the limbic-hypothalamic nuclei provides another important facet of estrogenic modulation of CCK induction. © 1996 John Wiley & Sons, Inc.     

Antitubulin effects of aminobenzothiophene-substituted triethylated chromones

In the course of our continuing studies on the 2-(benzo[b]thiophene-3′-yl)-6,8,8-triethyldesmosdumotin B (TEDB-TB) series, we designed and synthesized nine amino-TEDB-TB derivatives to improve pharmaceutical properties, identify structure activity relationships, and discover novel antitubulin agents. Among all newly synthesized amino-TEDB-TBs, the 5′- and 6′-amino derivatives, 6 and 7, exhibited significant antiproliferative activity against five human tumor cell lines, including an MDR subline overexpressing P-gp. The IC₅₀ values of 0.50–1.01 µM were 3–6 times better than those of previously reported hydroxy-TEDB-TBs. Compounds 6 and 7 inhibited tubulin polymerization, induced both depolymerization of interphase microtubules and multiple spindle formations, and caused cell arrest at prometaphase. Among all compounds, compound 7 scored best pharmaceutically with LogP 2.11 and biologically with greater antiproliferative activity and induction of cell cycle arrest at prometaphase.     

Design,synthesis and preliminary antiproliferative activity studies of new diheteroaryl thioether derivatives

A series of structurally new diheteroaryl thioether analogs was designed, prepared and screened toward MGC-803, MKN-45, EC-109 and H1650. Most of the target compounds displayed moderate to potent antiproliferative activities. Among them, compound 5 showed the best antiproliferative activity against the tested cell lines with the half maximal inhibitory concentration (IC₅₀) values below 10 μM. In addition, flow cytometry analysis showed that compound 5 increased Bax expression, down-regulated expression of Bcl-2, cleaved caspases-3/9, finally inducing apoptosis of MKN-45 cells as well as arrested the cell cycle at G2/M phase. This study suggests that the diheteroaryl thioethers are a class of emerging chemotypes for developing antitumor agents or biological probes, and compound 5 could serve as a good starting point to design new apoptosis inducers.