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Toxic contaminants and their biological effects in coastal waters of Xiamen, China. II. Biomarkers and embryo malformation rates as indicators of pollution stress in fish.

Baseline information is presented on embryo malformation rate and biomarkers in fish as indicators of sub-lethal stress caused by pollution in coastal waters of Xiamen, PR China. Fish and eggs were sampled from several areas in Xiamen coastal waters (Xiamen Harbour, Maluan and Tongan Bays and East Channel), where varying levels of pollutant input have been documented. Comparative sampling was done at a "cleaner" reference site at Dongshan Island. Embryonic malformation rates, which indicate general water quality, varied with location and species of fish, and exceeded background levels for unpolluted waters (assumed approximately 5%) by up to eightfold at some sites. Generally, sites around Xiamen Harbour show signs of poor water quality having highest mean levels of embryo deformity (20-30%) and these decreased towards open waters (Tongan Bay, Eastern Channel) where abnormalities approached background levels. An indication that toxic contaminants may be having a localised effect in the region, particularly in the harbour was reinforced by the biomarker assays. However, activities of the biomarkers ethoxyresorufin O-deethylase (EROD) and glutathione S-transferase in fish livers indicate no clear pattern, and there is no evidence that fish from the four sampling areas have been more or less exposed to PAHs and other compounds that induce these biomarkers. Antioxidant biomarkers (glutathione peroxidase, catalase, superoxide dismutase, and reduced glutathione) suggest that exposure to xenobiotics appears to be lowest in Dongshan and Maluan and highest in the harbour and Tongan. Inhibition of acetylcholinesterase in fish muscle indicated possible effects by organophosphate and carbamate pesticides in Xiamen waters and these effects may be greatest in the area of the harbour.

Acetylcholinesterase↗

Region-dependent dynamics of cAMP response element-binding protein phosphorylation in the basal ganglia.

The cAMP response element-binding protein (CREB) is an activity-dependent transcription factor that is involved in neural plasticity. The kinetics of CREB phosphorylation have been suggested to be important for gene activation, with sustained phosphorylation being associated with downstream gene expression. If so, the duration of CREB phosphorylation might serve as an indicator for time-sensitive plastic changes in neurons. To screen for regions potentially involved in dopamine-mediated plasticity in the basal ganglia, we used organotypic slice cultures to study the patterns of dopamine- and calcium-mediated CREB phosphorylation in the major subdivisions of the striatum. Different durations of CREB phosphorylation were evoked in the dorsal and ventral striatum by activation of dopamine D1-class receptors. The same D1 stimulus elicited (i) transient phosphorylation (</=15 min) in the matrix of the dorsal striatum; (ii) sustained phosphorylation (</=2 hr) in limbic-related structures including striosomes, the nucleus accumbens, the fundus striati, and the bed nucleus of the stria terminalis; and (iii) prolonged phosphorylation (up to 4 hr or more) in cellular islands in the olfactory tubercle. Elevation of Ca2+ influx by stimulation of L-type Ca2+ channels, NMDA, or KCl induced strong CREB phosphorylation in the dorsal striatum but not in the olfactory tubercle. These findings differentiate the response of CREB to dopamine and calcium signals in different striatal regions and suggest that dopamine-mediated CREB phosphorylation is persistent in limbic-related regions of the neonatal basal ganglia. The downstream effects activated by persistent CREB phosphorylation may include time-sensitive neuroplasticity modulated by dopamine.

3-Pyridinecarboxylic acid, 1,4-dihydro-2,6-dimethy↗

A differentially methylated imprinting control region within the Kcnq1 locus harbors a methylation-sensitive chromatin insulator.

The mechanisms underlying the phenomenon of genomic imprinting remain poorly understood. In one instance, a differentially methylated imprinting control region (ICR) at the H19 locus has been shown to involve a methylation-sensitive chromatin insulator function that apparently partitions the neighboring Igf2 and H19 genes in different expression domains in a parent of origin-dependent manner. It is not known, however, if this mechanism is unique to the Igf2/H19 locus or if insulator function is a common feature in the regulation of imprinted genes. To address this question, we have studied an ICR in the Kcnq1 locus that regulates long range repression on the paternally derived p57Kip2 and Kcnq1 alleles in an imprinting domain that includes Igf2 and H19. We show that this ICR appears to possess a unidirectional chromatin insulator function in somatic cells of both mesodermal and endodermal origins. Moreover, we document that CpG methylation regulates this insulator function suggesting that a methylation-sensitive chromatin insulator is a common theme in the phenomenon of genomic imprinting.

Alleles↗

RYR mutation G1021A (Gly341Arg) is not frequent in Danish and Swedish families with malignant hyperthermia susceptibility.

Malignant hyperthermia (MH) is a pharmacogenetic disorder. Susceptibility to MH (MHS) is presumed to be inherited in an autosomal dominant way. MH crises are triggered by halogenated inhalational anaesthetics and suxamethonium, and may be lethal if not treated early and adequately. Until now, eight mutations in the RYR1 gene have been described as causes of MHS phenotype in various MH families. The mutation RYR1 G1021A (Gly341Arg) has been reported to account for approximately 10% of Caucasian MHS cases. However, in our study this mutation was discovered in only 1 out of 89 Scandinavian families, indicating that this mutation may be the cause of MHS in only about 1% of MHS families in those populations. The mutation may have been brought to Scandinavia by an immigrant.

Calcium Channels↗

Connexin expression patterns in human trophoblast cells during placental development.

This study focuses on the gap junction expression pattern in trophoblast cells during human placental development in vivo and in vitro. Investigations of cell-cell communication properties within the subpopulations of trophoblast responsible for invasion, placental growth and feto-maternal transport seem of special interest because the intercellular channels are believed to coordinate proliferation and differentiation processes. From all gap junction connexins (Cx) investigated (Cx26, Cx31, Cx32, Cx37, Cx40, Cx43), Cx40 was the only connexin clearly detected within the cytotrophoblast of human placenta, and was restricted to the extravillous trophoblast of cell islands and cell columns. Most intense staining was found in the juxtastromal area correlated to the proliferating extravillous trophoblast cells. Connexin protein expression was missing during trophoblast migration into the decidua but was re-expressed in trophoblast aggregates within the decidua. Cx40 expression decreased with progressing pregnancy and no connexins could be detected in villous or extravillous trophoblast of mature placentae. In parallel, isolated trophoblast cells of first and second trimester placentae revealed Cx40 expression and, in contrast to the situation in vivo, Cx43 was also found. In isolated cells of mature placentae, expression of both Cx40 and Cx43 transcripts was decreased to low levels and Cx40 immunoreactivity was absent. Cx43 protein, however, was still detectable in trophoblast cultures of term placentae. Our studies suggest that Cx40 is the characteristic channel for the proliferating cell population of cell islands and cell columns of first and second trimester placentae and isolated trophoblast and is probably involved in regulation and coordination of the invasive pathway.

Cell Division↗

Genetic basis of total colourblindness among the Pingelapese islanders.

Complete achromatopsia is a rare, autosomal recessive disorder characterized by photophobia, low visual acuity, nystagmus and a total inability to distinguish colours. In this disease, cone photoreceptors, the retinal sensory neurons mediating colour vision, seem viable but fail to generate an electrical response to light. Achromatopsia, or rod monochromatism, was first mapped to 2p11-2q12 (MIM 216900; ref. 3), where it is associated with missense mutations in CNGA3 (ref. 4). CNGA3 encodes the alpha-subunit of the cone cyclic nucleotide-gated cation channel, which generates the light-evoked electrical responses of cone photoreceptors. A second locus at 8q21-q22 has been identified among the Pingelapese islanders of Micronesia, who have a high incidence of recessive achromatopsia (MIM 262300). Here we narrow the achromatopsia locus to 1.4 cM and show that Pingelapese achromatopsia segregates with a missense mutation at a highly conserved site in CNGB3, a new gene that encodes the beta-subunit of the cone cyclic nucleotide-gated cation channel. Two independent frameshift deletions establish that achromatopsia is the null phenotype of CNGB3. Combined with earlier findings, our results demonstrate that both alpha- and beta-subunits of the cGMP-gated channel are essential for phototransduction in all three classes of cones.

Adolescent↗

The cold-water coral Lophelia pertusa (Scleractinia) and enigmatic seabed mounds along the north-east Atlantic margin: are they related?

In this study, an updated distribution of Lophelia pertusa between the Porcupine Seabight and Norwegian shelf is presented. It seems unlikely that enigmatic mound structures observed at water depths of more than 570 m during acoustic seabed surveys, particularly to the west of the Shetland Islands, are related to the occurrence of L. pertusa. At these depths in the Faroe-Shetland Channel, the predominant influence of cold Arctic water precludes its growth. Iceberg dumpsites are also considered unlikely explanations for the origin of these mounds, and they are interpreted as most likely to be related to the release of fluids at the seabed. When mound structures were investigated, no scleractinian corals were recovered at water depths >500 m. This study shows the importance of seabed temperature as an environmental control on cold-water coral distribution. The significance of cold-water coral habitats in sustaining high levels of local-scale biodiversity is now becoming apparent in parallel with increased hydrocarbon extraction and fishing activity beyond the shelf edge. There is growing evidence that these areas have been marked by the passage of deep-water trawls. It seems likely that trawling activity has already reduced the extent of cold-water coral distribution in this region of the north-east Atlantic.

Animals↗

Malignant hyperthermia susceptibility, an autosomal dominant disorder?

A large series of Swedish nuclear families, in which malignant hyperthermia (MH) reactions had occurred during anaesthesia, have been examined with respect to malignant hyperthermia susceptibility. In vitro contracture tests (IVCT) of muscle strips were conducted to diagnose MH status. Included in this series were some families where only one of the parents was tested by IVCT, while in 79 of the families both parents were tested by IVCT. Six known mutations in the gene encoding the calcium release channel of sarcoplasmic reticulum in skeletal muscle (the RYR1 gene), believed to cause MHS in man, were searched for in 41 nuclear families. The present paper focuses on findings in eight families, where both parents were malignant hyperthemia negative (MHN), while at least one child was either malignant hyperthermia susceptible (MHS) or malignant hyperthermia equivocal (MHE). There was no suggestion of non-paternity. The RYR1 mutations investigated were Arg163Cys, Gly341Arg, Ile403Met, Arg614Cys, Gly2433Arg and Arg2434His. No family had any of the six RYR1 mutations searched for.

Adolescent↗

Coulomb-blockade-induced bound quasiparticle states in a double-island structure.

We determine the low temperature shape of the Coulomb-blockade staircase in a superconducting double-island device. For an odd number of electrons, in the ground state the intrinsic quasiparticle is bound to the tunneling contact. For a single channel contact the gap between the ground state and the continuum of excited states is of the order of the Josephson energy E(J). The temperature dependence of the Coulomb-blockade step width is nonmonotonic, with the minimal width occurring at T(i) approximately E(J)/ln(square root DeltaE(J)/delta), where Delta and delta are, respectively, the superconducting gap and mean level spacing in the island. For an even number of electrons, the Coulomb enhancement of the Josephson energy is shown to be significantly stronger than that for a single grain coupled to a lead. If the electrostatic energy favors a single broken Cooper pair, the resulting quasiparticles are bound to the contact at T=0.

Journal Article↗

Malignant teratoid medulloepithelioma manifesting as a black epibulbar mass with expulsive hemorrhage.

An 18-year-old woman with malignant teratoid medulloepithelioma had an epibulbar, brown-black mass associated with expulsive hemorrhage and a limboscleral perforation. Histopathologically, a prominent pigmented neuroepithelial component was present and correlated to the black color of the mass. The massive hemorrhage is apparently related to rupture of necrotic and abnormal vascular channels within the angiomatous component of the neoplasm. Other mesenchymal elements included spindle-shaped cells, rhabdomyoblasts, and islands of hyaline cartilage.

Adolescent↗

Pertussis toxin blocks presynaptic glutamate receptors--a novel 'glutamateB' receptor in the lobster neuromuscular synapse.

Topical application of L-glutamate to the neuromuscular synapse of the lobster walking leg induced K+-dependent hyperpolarization in the presynaptic membrane. This presynaptic glutamate potential (PGP) was insensitive to Joro spider toxin (JSTX), a spider toxin which specifically blocks the postsynaptic glutamate receptor, but was blocked by pertussis toxin island activating protein (IAP) in a dose-dependent manner. IAP had little effect on the resting conductance channels in pre- and postsynaptic membranes. GTP gamma S, a hydrolysis-resistant analogue of GTP, reduced the PGP supporting the involvement of G-protein in generation of K+ activation. The results suggest that a new type of glutamate receptor exists in the presynaptic membrane in the crustacean neuromuscular synapse.

Animals↗

Cyclooxygenase expression during Helicobacter pylori infection in Mongolian gerbils.

We investigated the expression of cyclooxygenase-2 (COX-2) and COX-1 mRNAs during longterm Helicobacter pylori infection of the Mongolian gerbil (18 months) as well as the effect of eradication therapy and the cag pathogenicity island on COX mRNA expression. COX mRNA levels were determined by reverse transcription-polymerase chain reaction. Pyloric channel ulcers were noted in one of 10 gerbils (10%) at 3 months, 33% at 6 months, 50% at 9 months, 17% at 10 months, 40% at 12 months and 25% at 18 months after inoculation of parental strains. Nineteen of 21 gerbils had successful H. pylori eradication and showed significant reduction of inflammation and no ulcerations. There were no significant differences in COX-1 mRNA expression between the groups. COX-2 mRNA expression was significantly increased 1 and 3 months after inoculation and then decreased to basal levels. In control animals, COX-2 mRNA expression was significantly higher at 12 and 18 months compared to younger animals. cagE knockout mutants did not induce gastric inflammation and induced significantly lower COX-2 mRNA expression compared to parental strains. COX-2 mRNA was induced early in H. pylori infection and then declined. COX-2 mRNA expression was also induced with aging.

Animals↗

A reflected energy prediction model for long-range hydroacoustic reflection in the oceans.

Acoustic energy from underwater earthquakes and explosions can propagate over long distances with very little attenuation in the deep ocean. When this sound encounters a seamount, island, or continental margin, it can scatter and again propagate over long distances. Hydrophones in the deep sound channel can detect these reflections tens of minutes or hours after arrivals from the direct source-to-receiver path. This paper presents the Reflected Energy Prediction (REP) model, a model for predicting these reflected arrivals. For a given source and receiver, the REP model uses a detailed knowledge of the underwater environment and components of the Hydroacoustic Coverage Assessment Model, HydroCAM, to predict the impulse response of the ocean. When this impulse response is convolved with a source function, a waveform envelope prediction is made that can be compared with recorded data. In this paper we present the model and a few applications of the model using data recorded from earthquakes and explosions in the Atlantic and Indian Oceans. These examples illustrate the use of the model and initial steps toward model calibration.

Journal Article↗

Reduction in muscle fibre number during the adaptive radiation of notothenioid fishes: a phylogenetic perspective.

The fish fauna of the continental shelf of the Southern Ocean is dominated by a single sub-order of Perciformes, the Notothenioidei, which have unusually large diameter skeletal muscle fibres. We tested the hypothesis that in fast myotomal muscle a high maximum fibre diameter (FD(max)) was related to a reduction in the number of muscle fibres present at the end of the recruitment phase of growth. We also hypothesized that the maximum fibre number (FN(max)) would be negatively related to body size, and that both body size and size-corrected FN(max) would show phylogenetic signal (tendency for related species to resemble each other). Finally, we estimated ancestral values for body size and FN(max). A molecular phylogeny was constructed using 12S mitochondrial rRNA sequences. A total of 16 species were studied from the Beagle Channel, Tierra del Fuego (5-11 degrees C), Shag Rocks, South Georgia (0.5-4 degrees C), and Adelaide Island, Antarctic Peninsula (-1.5 to 0.5 degrees C). The absence of muscle fibres of less than 10 micro m diameter was used as the criterion for the cessation of fibre recruitment. FD(max) increased linearly with standard length (SL), reaching 500-650 micro m in most species. Maximum body size was a highly significant predictor of species variation in FN(max), and both body size and size-corrected FN(max) showed highly significant phylogenetic signal (P<0.001). Estimates of trait values at nodes of the maximum likelihood phylogenetic tree were consistent with a progressive reduction in fibre number during part of the notothenioid radiation, perhaps serving to reduce basal energy requirements to compensate for the additional energetic costs of antifreeze production. For example, FN(max) in Chaenocephalus aceratus (12 700+/-300, mean +/- S.E.M., N=18) was only 7.7% of the value found in Eleginops maclovinus (164 000+/-4100, N=17), which reaches a similar maximum length (85 cm). Postembryonic muscle fibre recruitment in teleost fish normally involves stratified followed by mosaic hyperplasia. No evidence for this final phase of growth was found in two of the most derived families (Channichthyidae and Harpagiferidae). The divergence of the notothenioids in Antarctica after the formation of the Antarctic Polar Front and more recent dispersal north would explain the high maximum diameter and low fibre number in the derived sub-Antarctic notothenioids. These characteristics of notothenioids may well restrict their upper thermal tolerance, particularly for Champsocephalus esox and similar Channichthyids that lack respiratory pigments.

Adaptation, Biological↗

A search for three known RYR1 gene mutations in 41 Swedish families with predisposition to malignant hyperthermia.

Eight mutations in the gene (the RYR1 gene) encoding the calcium release channel of sarcoplasmic reticulum (SR) in skeletal muscle are so far known to be very closely linked to malignant hyperthermia susceptibility in man and are regarded to be causative. We have examined 41 Swedish families where malignant hyperthermia had occurred in at least one member during anaesthesia, with respect to three of the known mutations. The mutations were Arg163Cys; Ile403Met and Arg614Cys (also known as the "pig mutation"). In three (i.e. 7%) of the families we detected the Arg614Cys mutation, and this was the only one of the mutations searched for that was observed. This indicates that other mutations than those searched for in this study must cause malignant hyperthermia susceptibility in most Swedish malignant hyperthermia susceptible families.

Adult↗

Island flap perineoplasty for coverage of perineal skin defects after repair of cloacal deformity.

BACKGROUND: Traumatic cloacal defect is an injury sustained during childbirth in which the anovaginal septum is completely disrupted and the anus and vagina open as a common channel. Such injuries result in complete faecal incontinence and are difficult to repair both in terms of improving function and obtaining skin closure. METHODS: Four cases of traumatic cloacal defect with a delayed presentation are illustrated here. All were treated with an overlapping anterior sphincter repair in combination with island flap perineoplasty to achieve skin closure. Anorectal function before and after surgery and the success of achieving primary wound healing were evaluated. RESULTS: In all four cases profound incontinence was found preoperatively; all patients returned to normal or near normal continence following overlapping anterior sphincter repair. Island flap perineoplasty was successful in achieving primary healing in all cases and no flaps were lost to necrosis. CONCLUSIONS: Island flap perineoplasty is an effective method of achieving skin closure after anterior sphincter repair of traumatic cloacal defects.

Adult↗

Comparison of the distribution of binding sites for the potassium channel ligands [125I]apamin, [125I]charybdotoxin and [125I]iodoglyburide in the rat brain.

Potassium channels represent a diverse and promising target for drug development. Pharmacological subtypes of K channels have begun to emerge based on the development of both organic molecules and peptide toxins which possess subtype selectivity. In order to evaluate the neuroanatomical distribution of these subtypes we have utilized the ligands [125I]apamin, [125I]charybdotoxin and [125I]iodoglyburide in an autoradiographic study of rat brain. In the rat brain, these ligands have selectivity for the low conductance Ca(2+)-activated, voltage-gated K channels and ATP-sensitive K channels respectively. The distribution of binding sites for these three ligands were distinctly different. [125I]Apamin binding was highest in various thalamic and hippocampal structures, while only low to moderate levels of [125I]charybdotoxin binding were seen in these regions. In contrast, very high levels of [125I]charbydotoxin were seen in white matter regions such as the lateral olfactory tract and fasciculus retroflexus. High levels of [125I]charybdotoxin binding were also seen in gray matter-containing regions such as the zona incerta, medial geniculate and superior colliculus, where low to moderate [125I]apamin binding was found. [125I]Iodoglyburide presented a more uniform binding with the highest levels in the globus pallidus, islands of Calleja, anteroventral nucleus of the thalamus and zonas reticulata of the substantia nigra. These results indicate that subtypes of K channels have very different distributions in the brain. As such, the results imply differing CNS actions for potential modulators of K channel subtypes.

Animals↗

Historical biogeography of the strepsirhine primates of Madagascar.

Lying some 400 km off the coast of southeastern Africa, Madagascar is the world's largest oceanic island. It has been in roughly the same position relative to its parent continent for 120 million years, and as a consequence its mammal fauna is unusual in composition, with a low number of major taxa but a high diversity at lower taxonomic levels. Among Madagascar's native terrestrial mammals, only the orders Primates, Rodentia, Carnivora and Insectivora are represented (plus, until recently, the enigmatic and endemic Bibymalagasia, and Artiodactyla in the form of semiaquatic pygmy hippopotamuses). This reflects the fact that terrestrial mammals are notoriously poor over-water dispersers; yet at the same time the ancestors of all of Madagascar's mammals had to have crossed a wide oceanic barrier to get to the island at various points during the Tertiary. Here I examine the palaeogeographic evidence for potential land bridge or 'stepping-stone' connections with adjacent continents from the Mesozoic through the Cenozoic, and review the fossil records and phylogenies of each of Madagascar's mammalian groups in an attempt to estimate the minimum number of crossings necessary to produce the island's current faunal composition. Probable monophyletic origins for each major group, and thus a smaller rather than a larger number of crossings of the Mozambique Channel, imply that this water barrier has acted as a powerful filter; so powerful that it is unclear whether any crossings would have been possible without some form of subaerial connection, however ephemeral, at least from time to time during the Tertiary. Clarification of how Madagascar's terrestrial mammal fauna may have originated is thus as likely to emerge from the geology of the seafloor surrounding the island as it is to come from the fossil record or from the internal and external relationships of its various components.

Animal Migration↗