Density dependence tests,are they?

A large number of time series of abundances of insects and birds from a variety of data sets were submitted to a new density dependence test. The results varied enormously between data sets, but the relation between the frequency of statistically significant density dependence (SSDD) and the length of the series was similar to that of the power curve of the test, making the results consistent with the hypothesis of the density-dependent model being universally applicable throughout the data used. Pest and non-pest species did not differ in the incidence of SSDD. The more sampling error present in the data, the higher the percentages of SSDD. This was expected given that the power of the test increases with increasing sampling error in the data. Many of the data used here, as well as in the literature, clearly violate the basic assumption of the test that the organism concerned should be univoltine and semelparous. Yet the incidence of SSDD was the same in univoltine as in bi/polyvoltine species and the same in semelparous organisms as in birds that are reproductively active in more than one year. The seasonal migrant Autographa gamma in Britain and Czechoslovakia and even rainfall data were found to have SSDD. Statistical significance, however, does not automatically lead to the conclusion of density-dependent regulation. Any series of random variables which are in a stochastic equilibrium, such as a series of independent, identically distributed, random variables, is typically described better by the alternative (density-dependent) model than by the null (density-independent) model. Significant test results were often obtained with sloppy data, with data that clearly violate the basic assumptions of the test and with other data where an interpretation of the results in terms of densitydependent regulation was absurd. Given the fact that other explanations have to be found for significant test results for all these cases, mechanisms other than regulation may very well be applicable too where the data are entirely appropriate for the test. The test is simply a data-based choice between a model without and one with a stochastic equilibrium. A time series as such does not contain any information about the causes of the fluctuation pattern, so that one cannot expect statistics to produce such information from that time series. A significant test result using suitable data is entirely consistent with the hypothesis of density-dependent regulation, but also with any other suitable hypotheses. Because the test results were generally consistent with the hypothesis of a universal applicability of the density-dependence model, a negative test result may only mean that the time series was not long enough for the density dependence that was present to become statistically significant. Positive results are difficult to interpret, but so are negative results. A final decision needs to be based not so much on the test result as on much detailed information about the population concerned. Because the density-dependence test does not test for the presence of the mechanism of density-dependent regulation and because of the loaded, multiple meanings of the term density-dependence, calling the test a test of statistical density dependence may be preferable.     

Whose turtles are they,anyway?

The hawksbill turtle (Eretmochelys imbricata), listed since 1996 by the IUCN as Critically Endangered and by the Convention on International Trade in Endangered Species (CITES) as an Appendix I species, has been the subject of attention and controversy during the past 10 years due to the efforts of some nations to re-open banned international trade. The most recent debate has centred on whether it is appropriate for Cuba to harvest hawksbills from shared foraging aggregations within her national waters. In this issue of Molecular Ecology, Bowen et al. have used molecular genetic data to show that such harvests are likely to have deleterious effects on the health of hawksbill populations throughout the Caribbean.     

Peptides in the Hydrozoa: are they transmitters?

A family of peptides with the carboxy-terminus Arg-Phe-amide has been localized to specific subpopulations of neurons in every cnidarian species examined. These neurons are typically sensory in character or are associated with smooth muscle. Although a transmitter role for these peptides has been suggested for anthozoans at neuromuscular synapses, no such evidence is available for hydrozoans. Instead there is evidence that RF-amides can be modulators of neuronal activity which takes the form of a biphasic (inhibitory then excitatory) response in vivo, while in vitro only the inhibitory response is seen. Voltage clamp studies of identified motor neurons showed large, transitory outward currents when Pol-RF-amide peptide was applied.     

Mitochondria: are they the seat of senescence?

The frequently quoted figure for the fractional univalent reduction of oxygen to superoxide in mitochondria is certainly too high by at least one order of magnitude. This is so because the higher number (2%) was derived from mitochondria whose cytochrome c oxidase was blocked with cyanide. Nevertheless, even the more correct number (0.1%) means that the production of O(2)(-) and H(2)O(2) in mitochondria is large and apt to result in damage to macromolecules in spite of such defensive enzymes as superoxide dismutases and glutathione peroxidase. The data available for nematodes and flies provide a compelling case for the view that the accumulation of oxidative damage to specific mitochondrial proteins leads to the progressive dysfunction that we see as senescence. The data available from work with mammals are much weaker and do not yet allow a strong position to be taken.     

Brain-derived proteins in the CSF, do they correlate with brain pathology in CJD?

Background

Brain derived proteins such as 14-3-3, neuron-specific enolase (NSE), S 100b, tau, phosphorylated tau and Aβ_1–42 were found to be altered in the cerebrospinal fluid (CSF) in Creutzfeldt-Jakob disease (CJD) patients. The pathogenic mechanisms leading to these abnormalities are not known, but a relation to rapid neuronal damage is assumed. No systematic analysis on brain-derived proteins in the CSF and neuropathological lesion profiles has been performed.

Methods

CSF protein levels of brain-derived proteins and the degree of spongiform changes, neuronal loss and gliosis in various brain areas were analyzed in 57 CJD patients.

Results

We observed three different patterns of CSF alteration associated with the degree of cortical and subcortical changes. NSE levels increased with lesion severity of subcortical areas. Tau and 14-3-3 levels increased with minor pathological changes, a negative correlation was observed with severity of cortical lesions. Levels of the physiological form of the prion protein (PrP^c) and Aβ_1–42 levels correlated negatively with cortical pathology, most clearly with temporal and occipital lesions.

Conclusion

Our results indicate that the alteration of levels of brain-derived proteins in the CSF does not only reflect the degree of neuronal damage, but it is also modified by the localization on the brain pathology. Brain specific lesion patterns have to be considered when analyzing CSF neuronal proteins.     

Bone marrow derived cells in tumor angiogenesis and growth: are they the good,the bad or the evil?

Increasing evidence implicates an important role for a variety of bone marrow derived cells (BMDCs) in tumor angiogenesis and metastatic tumor growth. These cells are derived either from the hematopoietic or mesenchymal cell lineage, and they are distinguished, in part, by the expression of the panhematopoietic marker ‐ CD45. Some of these cell populations can colonize tumors perivascularily, and appear to promote angiogenesis and tumor cell proliferation by paracraine mechanisms, whereas others can contribute “directly” to the growth of tumor vessel capillaries or metastases. In this review we focus in particular on the role of hemangiocytes or recruited bone marrow derived circulating cells (RBCCs) in neovascularization, the contribution of VEGFR1+ hematopoietic stem cells and endothelial precursor cells in metastasis, and the involvement of myeloid derived suppressor CD11b+/Gr‐1+ cells in the resistance of tumors to certain antiangiogenic drugs, e.g., VEGF blocking antibodies.     

Do they or don't they? Presynaptic Receptors and the Question of Autoregulation of Neurotransmitter Release sponsored by the New York Academy of Sciences, Philadelphia, PA, USA, December 4-6, 1989

It is felt that the objectives of this conference were met and a great deal of new information was presented on the characterization of presynaptic receptors and their mechanisms of action and pathophysiological roles. There is still a difference of opinion concerning the precise physiological role of presynaptic autoreceptors. It is possible that autoregulation may not exist at all junctions or synapses. It is also not clear if autoregulation takes place at each varicosity, upstream of terminal varicosities, or by lateral regulation (one varicosity to another). Possible physiological functions of autoregulation may include: pulse-to-pulse regulation of transmitter release during nerve stimulation; upstream or lateral regulation of release from various varicosities; modulation of release during periods of rest or during periods in which the frequency of nerve stimulation is low; and modulation of release during periods of very intense stimulation. Finally, autoregulation may serve as a physiological antagonist to facilitation of transmitter release that is known to take place in some neurons during nerve stimulation. The conference provided a clearer understanding of the objections to attributing a physiological role to autoregulation and an understanding of what information is lacking. Challenges for future research will be to unravel the precise physiological and pathophysiological roles of presynaptic receptor-modulation of neurotransmission, to explain better why some results are inconsistent with the autoregulation hypothesis, and to define further the mechanisms by which activation of autoreceptors and heteroreceptors are linked to inhibition or facilitation of transmitter release.     

UV-induced changes in the skin: can they be repaired?

Abstract

The damaging effects of UVB light have been described previously and include a number of changes to multiple cell types. At previous meetings of this society, we have shown that Langerhans' cells are the most susceptible to UVB induced damage which can be shown as ultrastructural changes in dendrites, nucleus and cytoplasm by transmission electron microscopy. We have also shown that their patterns of migration from skin to regional lymph node and their ability to present antigens to autologous T cells have been profoundly altered by UVB irradiation.

The aim of this work was to establish if it was possible to reverse any of the damage done to Langerhans' cells by UVB exposure by topical application of a DNA repair enzyme such as T4N5 endonuclease. These experiments were undertaken in a sheep model that allowed collection of cells as they migrate from the skin. This allowed for a direct examination of the migration characteristics and ultrastructural features of all Langerhans' cells before, during, and for 2 weeks after exposure to a single dose of UVB.

Results obtained from this project indicate that treatment by topical application of DNA repair enzyme immediately after UVB irradiation may restore a number of normal immune parameters associated with the structure and function of migrating Langerhans' cells. It appears that there is a dose related correction of the increased tempo of cell migration and some improvements in the number of ultrastructurally damaged Langerhans' cells have also been associated with application of higher doses of DNA repair enzyme. These preliminary findings indicate that some potential therapeutic benefits are associated with the use of such agents in reversing the immunological damage caused by exposure to erythemal doses of UVB light.     

Ectoparasites: are they the proximate cause of cleaning interactions?

We tested the importance of ectoparasites in cleaning symbioses by comparing the activity of Caribbean cleaning gobies ( Elacatinus evelynae ) and of their clients during three daily periods (early morning, midday and late afternoon) in which ectoparasite availability varied naturally. Emergence from the benthos of gnathiid isopod larvae, the main target of cleaning goby predation, was higher at night, when cleaners are inactive, than during the day. Overall ectoparasite loads also tended to be higher on clients in the morning. This coincided with higher rates of visits to cleaning stations by client fish in the morning than at midday, but high rates of client visits were also recorded in the late afternoon. Clients were more likely to adopt stereotypical incitation poses, which increase the likelihood of being cleaned, in the morning than later in the day. Inspection bouts by cleaning gobies were longest in the morning. Cleaner and client behaviours therefore change predictably in response to natural diurnal variation in ectoparasite availability. These results add to a growing number of studies supporting the idea that cleaning symbioses are mutualisms dependent on ectoparasite removal.     

Kinins, receptors, kininases and inhibitors--where did they lead us?

Based on studies presented here and other published experiments performed with surviving tissue preparations, with transfected cells and with cells that constitutively express the human angiotensin I converting enzyme ACE and B2 receptors, we concluded the following: ACE inhibitors and other endogenous peptides that react with the active site of ACE potentiate the effect of bradykinin and its ACE resistant peptide congeners on the B2 receptor. They also resensitize receptors which had been desensitized by the agonist. ACE and bradykinin receptors have to be sterically close, possibly forming a heterodimer, for the ACE inhibitors to induce an allosteric modification on the receptor. When ACE inhibitors augment bradykinin effects, they reduce the phosphorylation of the B2 receptor. The primary actions of bradykinin on the receptor are not affected by protein kinase C or phosphatase inhibitors, but the potentiation of bradykinin or the resensitization of the receptor by ACE inhibitors are abolished by the same inhibitors. The results with protein kinase C and phosphatase inhibitors indicate that another intermediate protein may be involved in the processes of signaling induced by ACE inhibitors, and that ACE inhibitors affect the signal transduction pathway triggered by bradykinin on the B2 receptor.