Behavioural genetics: worms seek that old beetle smell

Some nematodes eavesdrop on pheromonal signals to sniff out their elderly beetle hosts. This turns out to be yet another behaviour regulated by cGMP/PKG signalling.     

Genetic analysis of nicotinic signaling in worms and flies

The nicotinic acetylcholine receptor is among the most thoroughly characterized molecules in the nervous system, and its role in mediating fast cholinergic neurotransmission has been broadly conserved in both vertebrates and invertebrates. However, the accessory molecules that facilitate or regulate nicotinic signaling remain mostly unknown. One approach to identify such molecules is to use molecular genetics in a simple, experimentally accessible organism to identify genes required for nicotinic signaling and to determine the molecular identity of the mutant genes through molecular cloning. Because cellular signaling pathways are often highly conserved between different animal phyla, the information gained from studies of simple organisms has historically provided many critical insights into more complex organisms, including humans. Genetic screens essentially make no prior assumptions about the types of molecules involved in the process being studied; thus, they are well suited for identifying previously unknown components of cell signaling pathways. The sophisticated genetic tools available in organisms such as the nematode Caenorhabditis elegans and the fruit fly Drosophila melanogaster have also proven extremely powerful in elucidating complex biologic pathways in the absence of prior biochemical information and for assessing a molecule's in vivo function of in the context of an intact nervous system. This review describes how genetic analysis has been used to investigate nicotinic signaling mechanisms in worms and flies, and the prospects for using these studies to gain insight into nicotinic receptor function and regulation in humans.     

FGF signaling in flies and worms: more and more relevant to vertebrate biology

FGF signaling in the invertebrate model systems Drosophila melanogaster and Caenorhabditis elegans was initially most obviously involved in cell motility events. More recently, however, FGFs and FGF signaling in these systems have been shown to affect many additional cellular processes. This recent work has shown that the pleiotropies of these FGF receptors resemble those of their vertebrate counterparts, and, in many cases, serve as excellent models for understanding the fundamental molecular mechanisms controlling these events.     

New approaches to estimating the mutagenic potential of chemicals

New developments in mutagenic risk assessment have appeared in the past few years. New methods have been developed such asin vitro micronucleus assay for chromosomal alterations, comet assay for primary DNA damage, use of transgenic animals to detectin vivo gene mutations, and fluorescent in situ hybridization method to detect aneuploidy. Other new methods will be developed in the few next years, including the use of DNA chips and the use of molecular biological methods. Several micromethods have been developed to test a great number of chemical compounds. New concepts have appeared concerning interpretation of data, and particularly of thresholds especially in the case of aneugens; in some cases metabolic or mechanistic thresholds were demonstrated. Genotoxic studies are best integrated into toxicological testing: for example, some genotoxicity tests can be integrated into subacute toxicology; interpretation of data includes metabolism; and toxicokinetic data relate to other toxicological studies. Conversely, genotoxicity data can be used to interpret toxicology studies. This revised version was published online in July 2006 with corrections to the Cover Date.     

Disruption of androgen receptor signaling in males by environmental chemicals

Androgen-disruptors are environmental chemicals in that interfere with the biosynthesis, metabolism or action of endogenous androgens resulting in a deflection from normal male developmental programming and reproductive tract growth and function. Since male sexual differentiation is entirely androgen-dependent, it is highly susceptible to androgen-disruptors. Animal models and epidemiological evidence link exposure to androgen disrupting chemicals with reduced sperm counts, increased infertility, testicular dysgenesis syndrome, and testicular and prostate cancers. Further, there appears to be increased sensitivity to these agents during critical developmental windows when male differentiation is at its peak. A variety of in vitro and in silico approaches have been used to identify broad classes of androgen disrupting molecules that include organochlorinated pesticides, industrial chemicals, and plasticizers with capacity to ligand the androgen receptor. The vast majority of these synthetic molecules act as anti-androgens. This review will highlight the evidence for androgen disrupting chemicals that act through interference with the androgen receptor, discussing specific compounds for which there is documented in vivo evidence for male reproductive tract perturbations. This article is part of a Special Issue entitled 'Endocrine disruptors'.     

Evolution: to seek out new worlds

A recent study of stickleback 'ecomorphs' generated by independent speciation events in different freshwater lakes suggests that, despite historical contingency, natural selection can run in surprisingly similar ways on multiple occasions.     

Adaptation to nephrotoxic chemicals

Rats given gentamicin chronically become resistant to its nephrotoxic effects. To further explore this adaptation to nephrotoxicity, we gave male rats gentamicin 40 mg/kg/day for 12 days, then 80 mg/kg/day for 24 days. We then challenged them with 110 mg/kg/day of gentamicin for 9 days. Spermine was given 16 mg/kg/day for 42 days, then gentamicin challenge at 60 mg/kg/day for 9 days. Gossypol was given at 6 mg/kg/day for 19 days, then gentamicin at 60 mg/kg/day for 21 days. A fourth group of rats (controls) received 0.5 ml saline daily for 42 days and then received gentamicin 60 mg/kg/day for 9 days. Urine N-acetyl-beta-glucosaminidase (NAG) was measured 3 times weekly and serum creatinine was measured 5 times during the study. Each drug-treated rat increased its urine NAG from baseline values. After a period of drug administration, all NAG values returned to the predrug values. Then all animals were given gentamicin daily. NAG values increased 20-fold in the animals previously treated with saline but did not rise in the other groups. The serum creatinine frequently but not always changed in parallel with the NAG values. These observations indicate that adaptation to these nephrotoxic substances occurs and that cross-resistance to gentamicin is produced by spermine and gossypol.     

Non-traditional targets of endocrine disrupting chemicals: the roots of hormone signaling

The topic of endocrine disruption and the broad range of physiologicaleffects caused by endocrine disrupting chemicals (EDCs) canonly be meaningfully framed within an ecological and evolutionarycontext. Environmental pollutants and EDCs operate by disruptingthe "chemical communication" that coordinates signaling withinan organism. Here we discuss how EDCs are also able to disruptthe chemical communication between plants and soil bacterianecessary for initiating nitrogen-fixing symbiosis. We alsoexamine, through examples of pollutant-related impacts on awide range of invertebrates, the need for identifying emergingtargets of EDCs. We suggest broadening the defined field ofendocrine disruption to encompass the effects of synthetic chemicalsthat interfere with signaling and communication, not only withinan organism, but also between organisms and linking ecosystems.The ecological consequences of failing to recognize novel targetsof chemical pollutants and EDCs may be a net loss of biologicaldiversity and a further imbalance of the global nitrogen cycle.     

Behavioral genetics: guanylyl cyclase prompts worms to party

When it comes to foraging, there are two types of worm in the world: those who enjoy a party, and those who prefer to dine alone. Two recent reports describe roles for guanylyl cyclase in the neuromolecular signaling systems that effect this natural behavioral dimorphism.     

The resistance of tubificid worms to three common pollutants

Summary Tubificid worms have been shown to be quite tolerant to toxic materials such as lead, phenol, and zinc. Their median tolerance limit (Tl_m) for pH levels in modified Knop solution has been shown to be 5.8 to 9.7. Their Tl_m for lead was 49.0 pp, at pH 6.5 and 27.5 at a pH of 8.5. For sodium pentochlorophenate (PCP) the Tl_m was found to be 0.31 ppm at pH 7.5, 0.67 ppm at pH 8.6 and 1.4 ppm at pH 9.5. The Tl_m determined for zinc was 46.0 ppm at pH 7.5. The interactions of pH and these substances has been examined and discussed, and the importance of definition of the solution has been shown. The mechanism of toxicity for lead and zinc probably is the mucousmetal complex which precipitates on the body wall blocking the exchange of oxygen and carbon dioxide. This is similar to the reaction of these metals observed in the gills of fish. The toxic mechanism of PCP is possibly a biochemical interruption of oxidative phosphorylation. It is not a mucous-effecting mechanism because no mucous precipitate forms as with the metals. In each instance these experiments show tubificids with a quantitative resistance to lead, zinc and phenol greater than similar resistance recorded for various fish species. This provides a basis for quantitative evaluation of the resistant nature of these organisms that may be valuable in future studies of their association to polluted habitats.

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Zusammenfassung Tubificiden haben sich giftigen Materialen wie Blei, Phenyl-säure und Zink gegenüber ziemlich duldsam gezeigt. Ihre Durchschnitts-Duldsamkeitsgrenze (Tl_m) für pH Werte in modifizierter Knop-Lösung sind, wie gezeigt wurde, 5.8 bis 9.7. Ihre Tl_m für Blei war 49.0 ppm bei pH 6.5 and 27.5 bei pH 8.5. Es wurde gefunden, dass das Tl_m für Natrium Pentochlorophenate (PCP) 0.31 ppm bei pH 7.5, 0.67 ppm bei pH 8.5 und 1.4 ppm bei pH 9.5 war. Die festgestellte Tl_m für Zink war 46.0 ppm bei pH 7.5. Die Wechselwirkungen von pH and diesen Substanzen sind geprüft and diskutiert worden und die Wichtigkeit von Erklärung der Auflösung gezeigt. Der Giftigkeits-Mechanismus für Blei and Zink is wahrscheinlich der Schleim-Metall-Komplex, der, den Austausch von Sauerstoff und Kohlenstoffdioxyd blockend, an der Körperwand verflüssigt. Dieses ähnelt der Gegenwirkung der beobachteten Metalle in den Kiemen von Fischen. Der Gift-Mechanismus von PCP ist möhcherweise eine biochemische Unterbrechung sauerstoffartiger Phosphorilation. Es ist kein Schleim-wirkender Mechanismus, weil sich kein Schleim-Präpicitat formt wie bei den Metallen. In jedem Beispiel zeigen diese Experimente bei Tubifiziden einen grösseren quantitativen Widerstand für Blei, Zink und Phenylsäure als ähnliche Widerstände, die bei verschiedenen Fisch-Species registriert wurden. Dieses bildet eine Basis für quantitative Abschätzung des Widerstandes dieser Organismen, die vielleicht in späteren Studien mit ihrer Verbindung mit verunreinigten Fundorten wertvoll sein kann.

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Supported by Grant WP 00937-02. National Institute of Health.