Mitochondrial genes reveal cryptic diversity in plant-breeding frogs from Madagascar (Anura, Mantellidae, Guibemantis)

One group of mantellid frogs from Madagascar (subgenus Pandanusicola of Guibemantis) includes species that complete larval development in the water-filled leaf axils of rainforest plants. This group consists of six described species: G. albolineatus, G. bicalcaratus, G. flavobrunneus, G. liber, G. pulcher, and G. punctatus. We sequenced the 12S and 16S mitochondrial rRNA genes ( approximately 1.8 kb) from multiple specimens (35 total) of all six species to assess phylogenetic relationships within this group. All reconstructions strongly supported G. liber as part of the Pandanusicola clade, even though this species does not breed in plant leaf axils. This result confirms a striking reversal of reproductive specialization. However, all analyses also indicated that specimens assigned to G. liber include genetically distinct allopatric forms that do not form a monophyletic group. Most other taxa that were adequately sampled (G. bicalcaratus, G. flavobrunneus, and G. pulcher) likewise consist of several genetically distinct lineages that do not form monophyletic groups. These results suggest that many of the recognized species in this group are complexes of cryptic species.     

Ontogeny of human hepatic cytochromes P450

Significant changes in drug-metabolizing enzyme (DME) expression occur during ontogeny. Such changes can have a profound effect on therapeutic efficacy in the fetus and child, as well as the risk for adverse drug reactions. To gain a better understanding of DME ontogeny, enzyme contents for six key cytochromes P450 were measured in 240 human liver samples representing ages from 8 weeks gestation to 18 years. Where possible, both quantitative western blotting and activity assays with probe substrates were performed. Although oversimplified, the DME can be grouped into one of three categories. As typified by CYP3A7, some enzymes are expressed at their highest level during the first trimester and either remain at high concentrations or decrease during gestation and are silenced or expressed at low levels within 1-2 years after birth. These data cause one to query whether these enzymes have an important endogenous function. Representatives of a second group, CYP3A5 and CYP2C19, are expressed at relatively constant levels throughout gestation. Postnatal increases in CYP2C19 are observed within the first year, but not for CYP3A5. CYP2C9, 2E1, and 3A4 are more typical of a third group of enzymes that are not expressed or are expressed at low levels in the fetus with the onset of expression generally in either the second or third trimester. Substantial increases in expression are observed within the first 1-2 years after birth; however, considerable interindividual variability is observed in the immediate postnatal (1-6 months) onset or increase in expression of these enzymes, often resulting in a window of hypervariability.     

A new species of the clingfish genus <Emphasis Type="Italic">Apletodon</Emphasis> (Teleostei: Gobiesocidae) from Sao Tome and Principe,Eastern Central Atlantic

The clingfish Apletodon wirtzi sp. nov. is described on the basis of ten specimens and colour photos from Bombom Island, Principe Group, Sao Tome and Principe, eastern central Atlantic Ocean. The species is very small, apparently not exceeding 16 mm total length; it is characterized by having three pores in the mandibular canal, the head length 2.2–2.5 in standard length: SL, the head broad, head width in males 3.6–4.0 (mean 3.8) in SL, the snout in males long, more or less pointed, conical, preorbital length in males 3.1–4.0 in head length, the occipital region with a large pinkish blotch behind each eye (in alcohol specimens), and the lower sides of the body with a row of dark blotches, scattered with white spots in between. The new species is compared with other species of the genus; a key to the males of the four known species of the eastern Atlantic genus Apletodon is presented. Supplementary material to this paper is available in electronic format at     

Immunolocalization of hypochlorite-induced, catalase-bound free radical formation in mouse hepatocytes

The establishment of oxidants as mediators of signal transduction has renewed the interest of investigators in oxidant production and metabolism. In particular, H(2)O(2) has been demonstrated to play pivotal roles in mediating cell differentiation, proliferation, and death. Intracellular concentrations of H(2)O(2) are modulated by its rate of production and its rate of decomposition by catalase and peroxidases. In inflammation and infection, some of the H(2)O(2) is converted to hypochlorous acid, a key mediator of the host immune response against pathogens. In vivo HOCl production is mediated by myeloperoxidase, which uses excess H(2)O(2) to oxidize Cl(-). Mashino and Fridovich (Biochim. Biophys. Acta 956:63-69; 1988) observed that a high excess of HOCl over catalase inactivated the enzyme by mechanisms that remain unclear. The potential relevance of this as an alternative mechanism for catalase activity control and its potential impact on H(2)O(2)-mediated signaling and HOCl production compelled us to explore in depth the HOCl-mediated catalase inactivation pathways. Here, we demonstrate that HOCl induces formation of catalase protein radicals and carbonyls, which are temporally correlated with catalase aggregation. Hypochlorite-induced catalase aggregation and free radical formation that paralleled the enzyme loss of function in vitro were also detected in mouse hepatocytes treated with the oxidant. Interestingly, the novel immuno-spin-trapping technique was applied to image radical production in the cells. Indeed, in HOCl-treated hepatocytes, catalase and protein-DMPO nitrone adducts were colocalized in the cells' peroxisomes. In contrast, when hepatocytes from catalase-knockout mice were treated with hypochlorous acid, there was extensive production of free radicals in the plasma membrane. Because free radicals are short-lived species with fundamental roles in biology, the possibility of their detection and localization to cell compartments is expected to open new and stimulating research venues in the interface of chemistry, biology, and medicine.     

GABAA receptor RDL inhibits Drosophila olfactory associative learning

In both mammals and insects, neurons involved in learning are strongly modulated by the inhibitory neurotransmitter GABA. The GABAA receptor, resistance to dieldrin (Rdl), is highly expressed in the Drosophila mushroom bodies (MBs), a group of neurons playing essential roles in insect olfactory learning. Flies with increased or decreased expression of Rdl in the MBs were generated. Olfactory associative learning tests showed that Rdl overexpression impaired memory acquisition but not memory stability. This learning defect was due to disrupting the physiological state of the adult MB neurons rather than causing developmental abnormalities. Remarkably, Rdl knockdown enhanced memory acquisition but not memory stability. Functional cellular imaging experiments showed that Rdl overexpression abolished the normal calcium responses of the MBs to odors while Rdl knockdown increased these responses. Together, these data suggest that RDL negatively modulates olfactory associative learning, possibly by gating the input of olfactory information into the MBs.     

A silver bullet for the treatment of depression?

The search for a rapid-acting antidepressant has been a subject of intense research interest for several decades. The article by Lucas and colleagues in this issue of Neuron provides compelling evidence from preclinical animal models that drugs acting at the serotonin 5-HT(4) receptor could finally achieve this goal. However, caution is warranted, as results from animal studies are not always predictive of therapeutic actions in humans.     

Regulation of dendritic excitability by activity-dependent trafficking of the A-type K+ channel subunit Kv4.2 in hippocampal neurons

Voltage-gated A-type K+ channel Kv4.2 subunits are highly expressed in the dendrites of hippocampal CA1 neurons. However, little is known about the subcellular distribution and trafficking of Kv4.2-containing channels. Here we provide evidence for activity-dependent trafficking of Kv4.2 in hippocampal spines and dendrites. Live imaging and electrophysiological recordings showed that Kv4.2 internalization is induced rapidly upon glutamate receptor stimulation. Kv4.2 internalization was clathrin mediated and required NMDA receptor activation and Ca2+ influx. In dissociated hippocampal neurons, mEPSC amplitude depended on functional Kv4.2 expression level and was enhanced by stimuli that induced Kv4.2 internalization. Long-term potentiation (LTP) induced by brief glycine application resulted in synaptic insertion of GluR1-containing AMPA receptors along with Kv4.2 internalization. We also found evidence of Kv4.2 internalization upon synaptically evoked LTP in CA1 neurons of hippocampal slice cultures. These results present an additional mechanism for synaptic integration and plasticity through the activity-dependent regulation of Kv4.2 channel surface expression.     

Diversity in structural ultraviolet coloration among female sulphur butterflies (Coliadinae, Pieridae)

In some species of sulphur butterflies (Pieridae: Coliadinae) females as well as males display bright structural reflectance on their dorsal wing surfaces, although comparatively little attention has been paid to this coloration in females. We examined the spectral properties of female dorsal coloration and scale structure in three species of sulphurs for which published images show bright UV reflectance in females: the Neotropical Anteos clorinde and two species of Indo-Australian Eurema, E. hecabe and E. candida. In A. clorinde and E. hecabe, female UV reflectance is iridescent and produced by thin film interference in a system of ridges and lamellae, as it is in conspecific males. Female A. clorinde exhibit the same spatial distribution and chromaticity of UV reflectance as seen in males, but the UV reflectance in female E. hecabe is much smaller in area compared to that of conspecific males and is both less bright and less chromatic than observed in males. In contrast, UV reflectance in E. candida females is diffuse, and arises from a lack of pterin pigments in the wings, which permits a broad-band scattered reflection to be seen. This is the mechanism that is known to produce bright UV reflectance in females of the confamilial whites. Our results highlight the diversity of UV reflectances and underlying mechanisms in sulphurs and suggest multiple evolutionary pathways leading to this diversity in female sulphur butterflies.