bluuebunny/crossref_metadata_2025 huggingface dataset:
Global analysis of dauer gene expression inCaenorhabditis elegans
Authors: Wang John , Kim Stuart K.
Published: March 2003

The dauer is a developmental stage in C. elegans that exhibits increased longevity, stress resistance, nictation and altered metabolism compared with normal worms. We have used DNA microarrays to profile gene expression differences during the transition from the dauer state to the non-dauer state and after feeding of starved L1 animals, and have identified 1984 genes that show significant expression changes. This analysis includes genes that encode transcription factors and components of signaling pathways that could regulate the entry to and exit from the dauer state, and genes that encode components of metabolic pathways important for dauer survival and longevity. Homologs of C. elegans dauer-enriched genes may be involved in the disease process in parasitic nematodes.
Genetic analysis of zebrafishgli1andgli2reveals divergent requirements forgligenes in vertebrate development
Authors: Karlstrom Rolf O. , Tyurina Oksana V. , Kawakami Atsushi , Nishioka Noriyuki , Talbot William S. , Sasaki Hiroshi , Schier Alexander F.
Published: March 2003

Gli proteins regulate the transcription of Hedgehog (Hh) target genes. Genetic studies in mouse have shown that Gli1 is not essential for embryogenesis, whereas Gli2 acts as an activator of Hh target genes. In contrast, misexpression studies in Xenopus and cultured cells have suggested that Gli1 can act as an activator of Hh-regulated genes, whereas Gli2 might function as a repressor of a subset of Hh targets. To clarify the roles of gli genes during vertebrate development, we have analyzed the requirements for gli1 and gli2 during zebrafish embryogenesis. We report that detour (dtr) mutations encode loss-of-function alleles of gli1. In contrast to mouse Gli1mutants, dtr mutants and embryos injected with gli1antisense morpholino oligonucleotides display defects in the activation of Hh target genes in the ventral neuroectoderm. Mutations in you-too(yot) encode C-terminally truncated Gli2. We find that these truncated proteins act as dominant repressors of Hh signaling, in part by blocking Gli1 function. In contrast, blocking Gli2 function by eliminating full-length Gli2 results in minor Hh signaling defects and uncovers a repressor function of Gli2 in the telencephalon. In addition, we find that Gli1 and Gli2 have activator functions during somite and neural development. These results reveal divergent requirements for Gli1 and Gli2 in mouse and zebrafish and indicate that zebrafish Gli1 is an activator of Hh-regulated genes, while zebrafish Gli2 has minor roles as a repressor or activator of Hh targets.
A Balbiani body and the fusome mediate mitochondrial inheritance duringDrosophilaoogenesis
Authors: Cox Rachel T. , Spradling Allan C.
Published: March 2003

Maternally inherited mitochondria and other cytoplasmic organelles play essential roles supporting the development of early embryos and their germ cells. Using methods that resolve individual organelles, we studied the origin of oocyte and germ plasm-associated mitochondria during Drosophilaoogenesis. Mitochondria partition equally on the spindle during germline stem cell and cystocyte divisions. Subsequently, a fraction of cyst mitochondria and Golgi vesicles associates with the fusome, moves through the ring canals,and enters the oocyte in a large mass that resembles the Balbiani bodies ofXenopus, humans and diverse other species. Some mRNAs, includingoskar RNA, specifically associate with the oocyte fusome and a region of the Balbiani body prior to becoming localized. Balbiani body development requires an intact fusome and microtubule cytoskeleton as it is blocked by mutations in hu-li tai shao, while egalitarian mutant follicles accumulate a large mitochondrial aggregate in all 16 cyst cells. Initially, the Balbiani body supplies virtually all the mitochondria of the oocyte, including those used to form germ plasm, because the oocyte ring canals specifically block inward mitochondrial transport until the time of nurse cell dumping. Our findings reveal new similarities between oogenesis inDrosophila and vertebrates, and support our hypothesis that developing oocytes contain specific mechanisms to ensure that germ plasm is endowed with highly functional organelles.
Incomplete reactivation ofOct4-related genes in mouse embryos cloned from somatic nuclei
Authors: Bortvin Alex , Eggan Kevin , Skaletsky Helen , Akutsu Hidenori , Berry Deborah L. , Yanagimachi Ryuzo , Page David C. , Jaenisch Rudolf
Published: March 2003

The majority of cloned animals derived by nuclear transfer from somatic cell nuclei develop to the blastocyst stage but die after implantation. Mouse embryos that lack an Oct4 gene, which plays an essential role in control of developmental pluripotency, develop to the blastocyst stage and also die after implantation, because they lack pluripotent embryonic cells. Based on this similarity, we posited that cloned embryos derived from differentiated cell nuclei fail to establish a population of truly pluripotent embryonic cells because of faulty reactivation of key embryonic genes such asOct4. To explore this hypothesis, we used an in silico approach to identify a set of Oct4-related genes whose developmental expression pattern is similar to that of Oct4. When expression of Oct4and 10 Oct4-related genes was analyzed in individual cumulus cell-derived cloned blastocysts, only 62% correctly expressed all tested genes. In contrast to this incomplete reactivation of Oct4-related genes in somatic clones, ES cell-derived cloned blastocysts and normal control embryos expressed these genes normally. Notably, the contrast between expression patterns of the Oct4-related genes correlated with efficiency of embryonic development of somatic and ES cell-derived cloned blastocysts to term. These observations suggest that failure to reactivate the full spectrum of these Oct4-related genes may contribute to embryonic lethality in somatic-cell clones.
bHLH transcription factor Her5 links patterning to regional inhibition of neurogenesis at the midbrain-hindbrain boundary
Authors: Geling Andrea , Itoh Motoyuki , Tallafuß Alexandra , Chapouton Prisca , Tannhäuser Birgit , Kuwada John Y. , Chitnis Ajay B. , Bally-Cuif Laure
Published: March 2003

The midbrain-hindbrain (MH) domain of the vertebrate embryonic neural plate displays a stereotypical profile of neuronal differentiation, organized around a neuron-free zone (`intervening zone', IZ) at the midbrain-hindbrain boundary(MHB). The mechanisms establishing this early pattern of neurogenesis are unknown. We demonstrate that the MHB is globally refractory to neurogenesis,and that forced neurogenesis in this area interferes with the continued expression of genes defining MHB identity. We further show that expression of the zebrafish bHLH Hairy/E(spl)-related factor Her5 prefigures and then precisely delineates the IZ throughout embryonic development. Using morpholino knock-down and conditional gain-of-function assays, we demonstrate that Her5 is essential to prevent neuronal differentiation and promote cell proliferation in a medial compartment of the IZ. We identify one probable target of this activity, the zebrafish Cdk inhibitor p27Xic1. Finally, although the her5 expression domain is determined by anteroposterior patterning cues, we show Her5 does not retroactively influence MH patterning. Together, our results highlight the existence of a mechanism that actively inhibits neurogenesis at the MHB, a process that shapes MH neurogenesis into a pattern of separate neuronal clusters and might ultimately be necessary to maintain MHB integrity. Her5 appears as a partially redundant component of this inhibitory process that helps translate early axial patterning information into a distinct spatiotemporal pattern of neurogenesis and cell proliferation within the MH domain.
Thedead ringer/retainedtranscriptional regulatory gene is required for positioning of the longitudinal glia in theDrosophilaembryonic CNS
Authors: Shandala Tetyana , Takizawa Kazunaga , Saint Robert
Published: March 2003

The Drosophila dead ringer (dri, also known asretained, retn) gene encodes a nuclear protein with a conserved DNA-binding domain termed the ARID (AT-rich interaction domain). We show here that dri is expressed in a subset of longitudinal glia in theDrosophila embryonic central nervous system and that driforms part of the transcriptional regulatory cascade required for normal development of these cells. Analysis of mutant embryos revealed a role fordri in formation of the normal embryonic CNS. Longitudinal glia arise normally in dri mutant embryos, but they fail to migrate to their final destinations. Disruption of the spatial organization of thedri-expressing longitudinal glia accounts for the mild defects in axon fasciculation observed in the mutant embryos. Consistent with the late phenotypes observed, expression of the glial cells missing(gcm) and reversed polarity (repo) genes was found to be normal in dri mutant embryos. However, from stage 15 of embryogenesis, expression of locomotion defects (loco) andprospero (pros) was found to be missing in a subset of LG. This suggests that loco and pros are targets of DRI transcriptional activation in some LG. We conclude that dri is an important regulator of the late development of longitudinal glia.
BDNF gene replacement reveals multiple mechanisms for establishing neurotrophin specificity during sensory nervous system development
Authors: Agerman Karin , Hjerling-Leffler Jens , Blanchard Marie Pierre , Scarfone Eric , Canlon Barbara , Nosrat Christopher , Ernfors Patrik
Published: March 2003

Neurotrophins have multiple functions during peripheral nervous system development such as controlling neuronal survival, target innervation and synaptogenesis. Neurotrophin specificity has been attributed to the selective expression of the Trk tyrosine kinase receptors in different neuronal subpopulations. However, despite overlapping expression of TrkB and TrkC in many sensory ganglia, brain-derived neurotrophic factor (BDNF) and neurotrophin 3 (NT3) null mutant mice display selective losses in neuronal subpopulations. In the present study we have replaced the coding part of theBDNF gene in mice with that of NT3 (BDNFNT3/NT3)to analyse the specificity and selective roles of BDNF and NT3 during development. Analysis of BDNFNT3/NT3 mice showed striking differences in the ability of NT3 to promote survival, short-range innervation and synaptogenesis in different sensory systems. In the cochlea, specificity is achieved by a tightly controlled spatial and temporal ligand expression. In the vestibular system TrkB or TrkC activation is sufficient to promote vestibular ganglion neuron survival, while TrkB activation is required to promote proper innervation and synaptogenesis. In the gustatory system, NT3 is unable to replace the actions of BDNF possibly because of a temporally selective expression of TrkB in taste neurons. We conclude that there is no general mechanism by which neurotrophin specificity is attained and that specificity is achieved by (i) a tightly controlled spatial and temporal expression of ligands, (ii) different Trk receptors playing distinct roles within the same neuronal subpopulation, or (iii) selective receptor expression in sensory neuron subpopulations.
Developmental defects observed in hypomorphic anaphase-promoting complex mutants are linked to cell cycle abnormalities
Authors: Shakes Diane C. , Sadler Penny L. , Schumacher Jill M. , Abdolrasulnia Maziar , Golden Andy
Published: March 2003

In C. elegans, mutants in the anaphase-promoting complex or cyclosome (APC/C) exhibit defects in germline proliferation, the formation of the vulva and male tail, and the metaphase to anaphase transition of meiosis I. Oocytes lacking APC/C activity can be fertilized but arrest in metaphase of meiosis I and are blocked from further development. To examine the cell cycle and developmental consequences of reducing but not fully depleting APC/C activity, we analyzed defects in embryos and larvae of mat-1/cdc-27mutants grown at semi-permissive temperatures. Hypomorphic embryos developed to the multicellular stage but were slow to complete meiosis I and displayed aberrant meiotic chromosome separation. More severely affected embryos skipped meiosis II altogether and exhibited striking defects in meiotic exit. These latter embryos failed to produce normal eggshells or establish normal asymmetries prior to the first mitotic division. In developing larvae,extended M-phase delays in late-dividing cell lineages were associated with defects in the morphogenesis of the male tail. This study reveals the importance of dosage-specific mutants in analyzing molecular functions of a ubiquitously functioning protein within different cell types and tissues, and striking correlations between specific abnormalities in cell cycle progression and particular developmental defects.
On the turning ofXenopusretinal axons induced by ephrin-A5
Authors: Weinl Christine , Drescher Uwe , Lang Susanne , Bonhoeffer Friedrich , Löschinger Jürgen
Published: March 2003

The Eph family of receptor tyrosine kinases and their ligands, the ephrins,play important roles during development of the nervous system. Frequently they exert their functions through a repellent mechanism, so that, for example, an axon expressing an Eph receptor does not invade a territory in which an ephrin is expressed. Eph receptor activation requires membrane-associated ligands. This feature discriminates ephrins from other molecules sculpturing the nervous system such as netrins, slits and class 3 semaphorins, which are secreted molecules. While the ability of secreted molecules to guide axons,i.e. to change their growth direction, is well established in vitro, little is known about this for the membrane-bound ephrins. Here we set out to investigate – using Xenopus laevis retinal axons – the properties of substratum-bound and (artificially) soluble forms of ephrin-A5(ephrin-A5-Fc) to guide axons.

We find – as expected on the basis of chick experiments – that,when immobilised in the stripe assay, ephrin-A5 has a repellent effect such that retinal axons avoid ephrin-A5-Fc-containing lanes. Also, retinal axons react with repulsive turning or growth cone collapse when confronted with ephrin-A5-Fc bound to beads. However, when added in soluble form to the medium, ephrin-A5 induces growth cone collapse, comparable to data from chick.

The analysis of growth cone behaviour in a gradient of soluble ephrin-A5 in the `turning assay' revealed a substratum-dependent reaction ofXenopus retinal axons. On fibronectin, we observed a repulsive response, with the turning of growth cones away from higher concentrations of ephrin-A5. On laminin, retinal axons turned towards higher concentrations,indicating an attractive effect. In both cases the turning response occurred at a high background level of growth cone collapse. In sum, our data indicate that ephrin-As are able to guide axons in immobilised bound form as well as in the form of soluble molecules. To what degree this type of guidance is relevant for the in vivo situation remains to be shown.
A novel function forHedgehogsignalling in retinal pigment epithelium differentiation
Authors: Perron Muriel , Boy Sébastien , Amato Marcos A. , Viczian Andrea , Koebernick Katja , Pieler Tomas , Harris William A.
Published: March 2003

Sonic hedgehog is involved in eye field separation along the proximodistal axis. We show that Hh signalling continues to be important in defining aspects of the proximodistal axis as the optic vesicle and optic cup mature. We show that two other Hedgehog proteins, Banded hedgehog and Cephalic hedgehog,related to the mouse Indian hedgehog and Desert hedgehog, respectively, are strongly expressed in the central retinal pigment epithelium but excluded from the peripheral pigment epithelium surrounding the ciliary marginal zone. By contrast, downstream components of the Hedgehog signalling pathway, Gli2,Gli3 and X-Smoothened, are expressed in this narrow peripheral epithelium. We show that this zone contains cells that are in the proliferative state. This equivalent region in the adult mammalian eye, the pigmented ciliary epithelium, has been identified as a zone in which retinal stem cells reside. These data, combined with double labelling and the use of other retinal pigment epithelium markers, show that the retinal pigment epithelium of tadpole embryos has a molecularly distinct peripheral to central axis. In addition, Gli2, Gli3 and X-Smoothened are also expressed in the neural retina, in the most peripheral region of the ciliary marginal zone, where retinal stem cells are found in Xenopus,suggesting that they are good markers for retinal stem cells. To test the role of the Hedgehog pathway at different stages of retinogenesis, we activated the pathway by injecting a dominant-negative form of PKA or blocking it by treating embryos with cyclopamine. Embryos injected or treated at early stages display clear proximodistal defects in the retina. Interestingly, the main phenotype of embryos treated with cyclopamine at late stages is a severe defect in RPE differentiation. This study thus provides new insights into the role of Hedgehog signalling in the formation of the proximodistal axis of the eye and the differentiation of retinal pigment epithelium.
Conditional loss of PTEN leads to testicular teratoma and enhances embryonic germ cell production
Authors: Kimura Tohru , Suzuki Akira , Fujita Yukiko , Yomogida Kentaro , Lomeli Hilda , Asada Noriko , Ikeuchi Megumi , Nagy Andras , Mak Tak W. , Nakano Toru
Published: March 2003

The tumor suppressor gene PTEN, which is frequently mutated in human cancers, encodes a lipid phosphatase for phosphatidylinositol 3,4,5-triphosphate [PtdIns(3,4,5)P3] and antagonizes phosphatidylinositol 3 kinase. Primordial germ cells (PGCs), which are the embryonic precursors of gametes, are the source of testicular teratoma. To elucidate the intracellular signaling mechanisms that underlie germ cell differentiation and proliferation, we have generated mice with a PGC-specific deletion of the Pten gene. Male mice that lacked PTEN exhibited bilateral testicular teratoma, which resulted from impaired mitotic arrest and outgrowth of cells with immature characters. Experiments with PTEN-null PGCs in culture revealed that these cells had greater proliferative capacity and enhanced pluripotent embryonic germ (EG) cell colony formation. PTEN appears to be essential for germ cell differentiation and an important factor in testicular germ cell tumor formation.
Regulation of Wingless and Vestigial expression in wing and haltere discs ofDrosophila
Authors: Prasad Mohit , Bajpai Ruchi , Shashidhara L. S.
Published: March 2003

In the third thoracic segment of Drosophila, wing development is suppressed by the homeotic selector gene Ultrabithorax (Ubx)in order to mediate haltere development. Previously, we have shown thatUbx represses dorsoventral (DV) signaling to specify haltere fate. Here we examine the mechanism of Ubx-mediated downregulation of DV signaling. We show that Wingless (Wg) and Vestigial (Vg) are differentially regulated in wing and haltere discs. In wing discs, although Vg expression in non-DV cells is dependent on DV boundary function of Wg, it maintains its expression by autoregulation. Thus, overexpression of Vg in non-DV cells can bypass the requirement for Wg signaling from the DV boundary. Ubxfunctions, at least, at two levels to repress Vestigial expression in non-DV cells of haltere discs. At the DV boundary, it functions downstream of Shaggy/GSK3β to enhance the degradation of Armadillo (Arm), which causes downregulation of Wg signaling. In non-DV cells, Ubx inhibits event(s) downstream of Arm, but upstream of Vg autoregulation. Repression of Vg at multiple levels appears to be crucial for Ubx-mediated specification of the haltere fate. Overexpression of Vg in haltere discs is enough to override Ubx function and cause haltere-to-wing homeotic transformations.
Knock-in of integrin β1D affects primary but not secondary myogenesis in mice
Authors: Cachaço Ana Sofia , Chuva de Sousa Lopes Susana M. , Kuikman Ingrid , Bajanca Fernanda , Abe Kuniya , Baudoin Christian , Sonnenberg Arnoud , Mummery Christine L. , Thorsteinsdóttir Sólveig
Published: March 2003

Integrins are extracellular matrix receptors composed of αand β subunits involved in cell adhesion, migration and signal transduction. The β1 subunit has two isoforms, β1A ubiquitously expressed and β1D restricted to striated muscle. They are not functionally equivalent. Replacement of β1A byβ 1D (β1D knock-in) in the mouse leads to midgestation lethality on a 50% Ola/50% FVB background [Baudoin, C., Goumans, M. J.,Mummery, C. and Sonnenberg, A.(1998). Genes Dev.12, 1202-1216]. We crossed the β1D knock-in line into a less penetrant genetic background. This led to an attenuation of the midgestation lethality and revealed a second period of lethality around birth. Midgestation death was apparently not caused by failure in cell migration, but rather by abnormal placentation. The β1D knock-in embryos that survived midgestation developed until birth, but exhibited severely reduced skeletal muscle mass. Quantification of myotube numbers showed that substitution ofβ 1A with β1D impairs primary myogenesis with no direct effect on secondary myogenesis. Furthermore, long-term primary myotube survival was affected in β1D knock-in embryos. Finally,overexpression of β1D in C2C12 cells impaired myotube formation while overexpression of β1A primarily affected myotube maturation. Together these results demonstrate for the first time distinct roles forβ 1 integrins in primary versus secondary myogenesis and that theβ 1A and β1D variants are not functionally equivalent in this process.
Ahedgehoghomolog regulates gut formation in leech(Helobdella)
Authors: Kang Dongmin , Huang Françoise , Li Dongling , Shankland Marty , Gaffield William , Weisblat David A.
Published: March 2003

Signaling by the hedgehog (hh)-class gene pathway is essential for embryogenesis in organisms ranging from Drosophila to human. We have isolated a hh homolog (Hro-hh) from a lophotrochozoan species, the glossiphoniid leech, Helobdella robusta,and examined its expression by reverse transcription polymerase chain reaction(RT-PCR) and whole-mount in situ hybridization. The peak of Hro-hhexpression occurs during organogenesis (stages 10-11). No patterned expression was detected within the segmented portion of the germinal plate during the early stages of segmentation. In stage 10-11 embryos, Hro-hh is expressed in body wall, foregut, anterior and posterior midgut, reproductive organs and in a subset of ganglionic neurons. Evidence that Hro-hhregulates gut formation was obtained using the steroidal alkaloid cyclopamine,which specifically blocks HH signaling. Cyclopamine induced malformation of both foregut and anterior midgut in Helobdella embryos, and no morphologically recognizable gonads were seen. In contrast, no gross abnormalities were observed in the posterior midgut. Segmental ectoderm developed normally, as did body wall musculature and some other mesodermal derivatives, but the mesenchymal cells that normally come to fill most of the coelomic cavities failed to develop. Taken with data from Drosophilaand vertebrates, our data suggest that the role of hh-class genes in gut formation and/or neural differentiation is ancestral to the bilaterians,whereas their role in segmentation evolved secondarily within the Ecdysozoa.
HIF1α is a critical regulator of secretory differentiation and activation, but not vascular expansion, in the mouse mammary gland
Authors: Seagroves Tiffany N. , Hadsell Darryl , McManaman Jim , Palmer Carol , Liao Debbie , McNulty Wayne , Welm Bryan , Wagner Kay-Uwe , Neville Margaret , Johnson Randall S.
Published: March 2003

During pregnancy the mammary epithelium and its supporting vasculature rapidly expand to prepare for lactation, resulting in dramatic changes in the micro-environment. In order to investigate the role of oxygenation and metabolism in these processes, the oxygen-responsive component of the hypoxia-inducible factor (HIF) 1 complex, HIF1α, was deleted in the murine mammary gland. Although vascular density was unchanged in the HIF1α null mammary gland, loss of HIF1α impaired mammary differentiation and lipid secretion, culminating in lactation failure and striking changes in milk composition. Transplantation experiments confirmed that these developmental defects were mammary epithelial cell autonomous. These data make clear that HIF1α plays a critical role in the differentiation and function of the mammary epithelium.
Middle Jurassic turtles from southern Thailand
Authors: TONG HAIYAN , BUFFETAUT ERIC , SUTEETHORN VARAVUDH
Published: March 2003

A new genus and species of primitive cryptodiran turtle, Siamochelys peninsularis n. g. n.
sp., from the Middle Jurassic Mab Ching locality, in the southern peninsula of Thailand, is described
on the basis of complete shells. They are characterized by a combination of primitive features (the
presence of a pair of mesoplastra meeting on the midline) and a series of derived characters (loose
plastron–carapace attachment, short diamond-shaped entoplastron, dorsal thickening of the lateral
edge of the second to seventh peripheral plates, expanded seventh to eleventh peripheral plates, extension
of the anal scute to the hyo-hypoplastral suture or onto the hypoplastron, midline sulcus sinusoidal),
and thus closely resemble Chengyuchelys, from the Middle Jurassic of China, and more
particularly Xinjiangchelys and its relatives from the Middle and Late Jurassic of China and Central
Asia. This supports a Middle Jurassic age for the locality and suggests that the Sibumasu (Shan-Thai)
block was in contact with the Asian mainland by that time.
Modelling the thermal perturbation of the continental crust
after intraplating of thick granitoid sheets: a comparison with
the crustal sections in Calabria (Italy)
Authors: CAGGIANELLI A. , PROSSER G.
Published: March 2003

Thick granitoid sheets represent a considerable percentage of Palaeozoic crustal sections
exposed in Calabria. High thermal gradients are recorded in upper and lower crustal regional metamorphic
rocks lying at the roof and base of the granitoids. Ages of peak metamorphism and emplacement
of granitoids are mostly overlapping, suggesting a connection between magma intrusion and
low-pressure metamorphism. To analyse this relationship, thermal perturbation following granitoid
emplacement has been modelled. The simulation indicates that, in the upper crust, the thermal perturbation
is short-lived. In contrast, in the lower crust temperatures greater than 700°C are maintained
for 12 Ma, explaining granulite formation, anatexis and the following nearly isobaric cooling. An even
longer perturbation can be achieved introducing the effect of mantle lithosphere thinning into the
model.
Mesozoic volcanism in the Middle East: geochemical,
isotopic and petrogenetic evolution of extension-related
alkali basalts from central Lebanon
Authors: ABDEL-RAHMAN ABDEL-FATTAH M.
Published: March 2003

Mesozoic picritic and alkali basalts from central Lebanon represent a significant part of an
extension-related Upper Jurassic to Upper Cretaceous discontinuous volcanic belt which occurs
throughout the Middle East. Volcanism was associated with an episode of intraplate extension that
followed a period of continental break-up, where Mesozoic micro-continental blocks separated from
Gondwana as the Neotethys ocean opened in Jurassic times. This volcanic episode produced mafic
lava flows ranging in thickness from 5 to 20 m, along with some minor pyroclastic flows. These flows
are stratigraphically intercalated with thick carbonate platform deposits. The basalts are made up of
about 15–20% olivine (Fo78–91), 30–35% clinopyroxene (salite), 40–50% plagioclase (An56–71) and
opaque Fe–Ti oxides (∼5%). Geochemically, the rocks exhibit a relatively wide range of SiO2 (40.4 to
50.5 wt%) and MgO (5.1 to 15.5 wt%) contents, are relatively enriched in TiO2 (1.7 to 3.7 wt%) and
vary in composition from alkali picrite and basanite to alkali basalt. The Mg numbers range from 0.56
to 0.70, with an average of 0.63. The rocks are enriched in incompatible trace elements such as Zr
(86–247 ppm), Nb (16–66 ppm) and Y (19–30 ppm). Such compositions are typical of those of
HIMU-OIB and plume-related magmas. The REE patterns are fractionated ((La/Yb)N = 11), LREE
enriched, and are generally parallel to subparallel. Elemental ratios such as K/P (1.1–4.7), La/Ta
(11–13), La/Nb (0.57–0.70), Nb/Y (0.68–1.55) and Th/Nb (0.20–0.36) suggest that crustal contamination
was minor or absent. This may be related to a rapid ascent of the magma, in agreement with the
nature (mafic, oceanic-like) and the small thickness (about 12 km) of the Mesozoic crust of the Eastern
Mediterranean region. The 143Nd/144Nd isotopic compositions of the lavas range from 0.512826 to
0.512886, and 87Sr/86Sr from 0.702971 to 0.703669, suggesting a HIMU-like mantle source. Trace element
compositions indicate a melt segregation depth of 100–110 km, well within the garnet lherzolite
stability field. The geochemical characteristics of the rocks are typical of within-plate alkali basalts,
and suggest that the magmas were derived from a fertile, possibly plume-related, enriched mantle
source. Petrogenetic modelling indicates that the magmas were produced by very small degrees of
batch partial melting (F = 1.5%) of a primitive garnet-bearing mantle source (garnet lherzolite).
Bio-signatures in metabasaltic glass of a Caledonian ophiolite, West Norway
Authors: FURNES HARALD , MUEHLENBACHS KARLIS , TORSVIK TERJE , TUMYR OLE , SHI LANG
Published: March 2003

Evidence of bioalteration of natural basaltic rocks, presently receiving much attention, has
so far been restricted to in situ oceanic crust and ophiolites in which fresh glass is still present. Here we
present evidence of preserved bio-signatures in the chilled margin of pillow lavas of an old (443 Ma)
ophiolite that has suffered pervasive lower greenschist facies metamorphism and deformation. X-ray
mapping of initial alteration zones shows the remains of organic carbon associated with highly-concentrated
Fe and S. Bioproduction of CO2 is further reflected in the low δ13C values of calcite
extracted from pillow rims, compatible with microbe-induced fractionation during oxidation of
organic matter. We attribute these effects to growth of sulphate-reducing bacteria at the early stage of
ophiolite formation. During energy metabolism these bacteria reduce sulphate to H2S and oxidize
organic matter to CO2 . Hydrogen sulphide will eventually react with iron and form pyrite, and carbon
dioxide is precipitated as calcium carbonate. The results of this study may thus trigger the search for
bio-signatures in glassy volcanic rocks of any age.
Spherulitic textures formed during crystallization of
partially melted arkose, Rum, Scotland
Authors: HOLNESS M. B.
Published: March 2003

Melting of Torridonian arkoses, due to intrusion of shallow bodies of mafic melts on the Isle of
Rum, was locally extensive, reaching up to 95 vol.%. Crystallization (to form granophyre) of these highly
melted rocks was generally static in the vicinity of minor intrusions, although disruption of bedding is
apparent in the aureole of the main mafic pluton. A distinctive millimetre- to centimetre-scale spherulitic
texture developed during solidification of the partially melted arkose, in both the aureole of the main
intrusion, and also in those of associated minor gabbro plugs. The spherulites are formed of radiating,
fan-shaped intergrowths of plagioclase and quartz set in a matrix of quartz, plagioclase and K-feldspar.
The importance of nucleation rates in determining texture development is demonstrated by a dominance
of Na-rich compositions in the first feldspar to form, even in non-spherulitic rocks. It is suggested that the
spherulites formed by the early growth of metastable plagioclase due to difficulties in nucleating feldspar.
The nature and regional significance of structures in the Gala
Group of the Southern Uplands terrane, Berwickshire coast,
southeastern Scotland
Authors: HOLDSWORTH R. E. , TAVARNELLI E. , CLEGG P.
Published: March 2003

Structures deforming Llandovery turbidites of the Gala Group in the Southern Uplands
terrane are spectacularly exposed in the Berwickshire coastal section, southeastern Scotland. The
upward-facing, upright to NW-vergent folds and associated structures appear to record a single
regional phase of subhorizontal NW–SE contractional deformation, with a steeply dipping direction
of bulk finite extension. These structures are markedly different from those developed in rocks correlated
with the Upper Llandovery Hawick Group exposed some 5 km to the south in the
Eyemouth–Burnmouth coastal section. Here a highly domainal system of sinistral transpressional
strain occurs, with zones of steeply plunging curvilinear folds, clockwise cleavage transection and
bedding-parallel sinistral detachment faults. The markedly different bulk strain patterns in the
Berwickshire coastal sections are thought to reflect the regionally diachronous nature of transpressional
deformation in the Southern Uplands terrane. There are striking similarities in the structures
recognized in the Berwickshire coastal sections and those developed in stratigraphically equivalent
units along strike in southwestern Scotland and Northern Ireland. This confirms the lateral structural
continuity and correlation of tracts and tract boundaries along the entire length of the Southern
Uplands terrane. The regional structure suggests that a phase of top-to-the-NW backthrusting and
backfolding associated with the southern margin of the Gala Group outcrop marks the transition
from orthogonal contraction to sinistral transpression in the Southern Upland thrust wedge during
late Llandovery times.
Whole-rock geochemical variations and evolution of
the arc-derived Murihiku Terrane, New Zealand
Authors: ROSER B. P. , COOMBS D. S. , KORSCH R. J. , CAMPBELL J. D.
Published: March 2003

Arc-flank volcaniclastic sedimentation in the Murihiku Terrane of New Zealand lasted
about 120 million years from Late Permian to Early Cretaceous time. Despite the effects of pervasive
zeolite-facies alteration, whole-rock geochemical parameters for sandstones, siltstones and tuffs
record changes in source-rock composition, both in time and along the length of the depositional
basin. Sandstones are considered to give a more reliable indication of the state of evolution of the
source volcanic arc than do the siltstones. The siltstones commonly contain detrital white mica flakes
that are generally lacking in the sandstones, and are possibly of distal continental origin. Some also
contain very fine felsic ash particles. Average abundances and normalized multi-element diagrams are
used to estimate proportions of three model end-member source constituents, average upper-continental
crust (UCC), high-K rhyolite (RHY) and basaltic andesite (AND). Sandstone provenance for the
Southland Syncline sector changed from a predominantly basaltic-andesite source in Late Permian to
early Middle Triassic time, for example, UCC:RHY:AND = 0:17:83 in the Early to early Middle
Triassic, to highly felsic in the Middle to Late Triassic, reaching UCC:RHY:AND = 2:74:24 in the
Late Triassic Oretian Stage. A UCC component became increasing significant from latest Triassic
upward and the proportion of mafic to felsic volcanism increased again, with UCC:RHY:AND =
15:30:35 in the Middle Jurassic Temaikan Stage. Mix modelling suggests that along-arc source proportions
varied, with greater mafic and upper continental crust contributions in the northern Kawhia segment
than in the Southland segment. These patterns may be explained by deposition at an oceanic
Aleutian-type arc margin, with transition to a continental oceanic arc character induced either by
arc evolution and dissection, forearc sliver translation, or underplating of rafted microcontinental
fragments.
Middle Devonian lycopsids from high southern
palaeolatitudes of Gondwana (Argentina)
Authors: CINGOLANI CARLOS A. , BERRY CHRISTOPHER M. , MOREL EDUARDO , TOMEZZOLI RENATA
Published: March 2003

Fossil plants are described from the upper part of the Devonian Lolén Formation, Sierra de
la Ventana, Buenos Aires Province, Argentina, in the area of Estancia Las Acacias. The sequence is
composed mainly of dark grey shales, and fossils were found in a single horizon where thin interlayered
beds of fine reddish-brown micaceous sandstones appear where the environment of marine
deposition became more shallow. The age of the Lolén Formation is presently established on the basis
of brachiopods, these being characteristic elements of the Malvinokaffric realm from the Gondwana
Lower Devonian (Emsian). The fossil plants are remarkably preserved given that they are in rocks that
have undergone intense deformation. The plants are identified as Haplostigma sp. and Haskinsia cf.
H. colophylla, and suggest a Middle Devonian age (Givetian) for the fossil-bearing levels. Haskinsia,
identified on the basis of leaf morphology, is the first well-delimited Middle Devonian lycopsid genus
described from Argentina, and the record from the most southerly palaeolatitude. During the Middle
Devonian, Haskinsia was distributed in tropical, warm temperate and high southern latitude, ?cool
temperate zones.
The initiation and early tectonic significance of the
Outer Hebrides Fault Zone, Scotland
Authors: IMBER J. , STRACHAN R. A. , HOLDSWORTH R. E. , BUTLER C. A.
Published: March 2003

The Outer Hebrides Fault Zone is a major ESE-dipping detachment exposed within basement
gneisses of the Archaean–Palaeoproterozoic Lewisian Complex, northwest Scotland. The fault
zone exhibits a long-lived displacement history and was active during Proterozoic, end-Silurian,
Carboniferous and Mesozoic times. The earliest deformation event preserved onshore was associated
with top-to-the-NW ductile thrusting. A previous study proposed that thrust-related protomylonitic
and mylonitic fabrics are cross-cut by amphibolites (‘Younger Basics’) and Laxfordian granite and
pegmatite sheets. This evidence was used to suggest that ductile thrusting occurred during the
Palaeoproterozoic Inverian event at c. 2500 Ma. Our observations demonstrate, however, that
mylonitic fabrics within the ductile thrust zone are superimposed on all components of the gneiss
complex including amphibolites and Laxfordian intrusions. It therefore follows that the Outer
Hebrides Fault Zone cannot be older than c. 1685 Ma, the age of recently dated Laxfordian granites in
the Outer Hebrides. Geochronological studies have shown that the basement blocks of the northern
Outer Hebrides and Scottish mainland have different geological histories and were amalgamated during
Proterozoic times at or after c. 1700 Ma. We propose that early ductile thrusting along the Outer
Hebrides Fault Zone formed part of this amalgamation process leading to burial and reheating of the
footwall gneisses in Lewis and north Harris. This would account for the c. 1100 Ma thermal event
recorded by previous workers and implies that ductile thrusting along the Outer Hebrides Fault Zone
is of Grenvillian age.
Morphological changes in the reproductive organs of male and female Schistosoma mansoni worms caused by streptozotocin, a drug used to induce diabetes mellitus
Authors: HULSTIJN M. , BARROS L. A. , NEVES R. H. , MOURA E. G. , MACHADO-SILVA J. R.
Published: March 2003

Host metabolic changes have been observed to affect Schistosoma mansoni egg production, worm survival and morphology. We examined worms recovered from streptozotocin-induced diabetic mice by morphometric and morphological analysis through brightfield and confocal laser scanning microscopy. Tegument thickness was slightly smaller and changes in the reproductive organs were observed in 23–30% and consecutively 88–100% of the worms. The testicular lobes had a large diminution of cells in one or more of the lobes, which was associated with a lack of spermatozoids in the seminal vesicle. Ovaries were atrophied, manifested by a complete or large reduction in oocytes but other parts of the reproductive system like the vitelline glands were mainly unaffected. Streptozotocin (STZ) instead of hyperglycaemia caused the degeneration since worms from mice injected with a non-diabetogenic dose, or with nicotinamide to prevent diabetes showed the same alterations. The drug did not affect worm survival or pairing. We conclude that STZ, an alkylating agent that provokes chromosome and DNA damage, changes the morphology of ovaries and testicular lobes in S. mansoni worms in vivo. This is the first report of STZ action in helminths and we suggest that STZ affects oogenesis and spermatogenesis and might cause sterilization of schistosomes.
Consequence of Hoechst 33342-mediated Leishmania DNA topoisomerase-I inhibition on parasite replication
Authors: MARQUIS J.-F. , DROLET M. , OLIVIER M.
Published: March 2003

This study reports that inhibition of Leishmania Topo-I with the minor groove-binding ligands (MGBLs) Hoechst 33342 (Ho342) blocks parasite growth in culture by mechanisms involving DNA breakage. While Ho342 inhibited the replication of several species of Leishmania in a dose- and time-dependent manner, Ho258 was not effective. Cytofluorometric analysis suggested that superior effectiveness of Ho342 over Ho258 was attributed to Leishmania parasites being more permeable toward Ho342. This observation was supported by the ability of both Ho342 and Ho258 to block the relaxation of supercoiled pBR322 DNA by Leishmania Topo-I. The Ho342 specificity toward L. donovani Topo-I was reinforced by the observation that increased Topo-I gene expression and Topo-I activity in Leishmania was paralleled by augmented resistance for this compound. Furthermore, the capacity of NaCl treatment to reverse MGBL-mediated DNA break suggests that Ho342 targetted Topo-I. Moreover, we observed that Ho342-inducible arrest of Leishmania growth was accompanied by G1 arrest and induction of cell death that closely resembles apoptosis. Taken together, our results suggest that MGBL compounds show promise as Topo-I inhibitors against Leishmania infection.
Association of Borrelia afzelii with rodents in Europe
Authors: HANINCOVÁ K. , SCHÄFER S. M. , ETTI S. , SEWELL H.-S. , TARAGELOVÁ V. , ZIAK D. , LABUDA M. , KURTENBACH K.
Published: March 2003

Borrelia burgdorferi sensu lato (s.l.) is maintained in nature by complex zoonotic transmission cycles, involving a large variety of vertebrates as hosts and hard ticks of the genus Ixodes as vectors. Recent studies suggest that the genospecies of B. burgdorferi s.l. and sometimes their subtypes are propagated by different spectra of hosts, mainly birds and rodents. In order to test the concept of host-association, we analysed the relationships between Borrelia genospecies, rodent hosts and I. ricinus ticks in an endemic focus of Lyme borreliosis in western Slovakia. Rodents and questing ticks were collected at a forested lowland locality near Bratislava. Tick infestation levels on rodents were determined, and spirochaete infections in ticks and in ear punch biopsies were analysed by PCR followed by genotyping. Mice were more heavily infested with ticks than bank voles, and a higher proportion of mice was infected with spirochaetes than voles. However, the infectivity of voles was much higher than that of mice. The vast majority of infections detected in the skin and in ticks feeding on the rodents represented B. afzelii. In contrast, more than half of all infections in questing ticks collected in the same region of Slovakia were identified as B. valaisiana and B. garinii. In conclusion, whilst the study reveals that mice and voles play different quantitative roles in the ecology of Lyme borreliosis, it demonstrates that B. afzelii is specifically maintained by European rodents, validating the concept of host-association of B. burgdorferi s.l.
On the interpretation of age–intensity profiles and dispersion patterns in parasitological surveys
Authors: DUERR H. P. , DIETZ K. , EICHNER M.
Published: March 2003

The present paper describes how age–intensity profiles of macroparasite burdens are affected by processes underlying the distribution of the parasite numbers in host populations. In a comparative way, we consider the following 6 processes: (i) age-dependent exposure, (ii) parasite-induced host mortality, (iii) heterogeneity within the host population, (iv) clumped infection, (v) density-dependent parasite mortality and (vi) density-dependent parasite establishment. For each of these processes, we show typical patterns in the age–intensity profile and provide, if possible, explicit and simple solutions for the age-dependent mean parasite burden and the corresponding dispersion patterns. Emphasis is given to density-dependent parasite establishment and to age–intensity profiles resulting from the superposition of different processes. By means of 2 examples we show that the interpretation of observed patterns can be ambiguous if more than 1 process takes place. These findings underline that age–intensity profiles should be interpreted on the basis of available a priori knowledge about the processes assumed to be involved. For purposes of testing different hypotheses, a simulation program is provided with which discrepancies between model prediction and data can be explored.
Detection of Opisthorchis viverrini in experimentally infected bithynid snails and cyprinoid fishes by a PCR-based method
Authors: MALEEWONG W. , INTAPAN P. M. , WONGKHAM C. , WONGSAROJ T. , KOWSUWAN T. , PUMIDONMING W. , PONGSASKULCHOTI P. , KITIKOON V.
Published: March 2003

A PCR procedure for the detection of Opisthorchis viverrini in experimentally infected bithynid snails and cyprinoid fishes was developed. This procedure was based on primers designed from a pOV-A6 specific probe sequence giving a 330 base-pair product. The detection was accomplished in host tissue homogenates to which a single cercaria or metacercaria was introduced. PCR can detect as little as a single cercaria artificially inoculated in a snail or a single metacercaria artificially inoculated in a fish sample. The method gave a 100% positivity rate for all infected snails or fishes. The method did not yield a 330 base-pair amplified product with other digenean fluke DNAs such as Haplorchis taichui, Centrocestus spp., Echinostoma malayanum, Fasciola gigantica, animal schistosomes, Paragonimus heterotremus or Haplorchoides spp. The assay has great potential for application in epidemiological surveys of both snail and fish intermediate hosts as well as for investigation of foodborne parasites in freshwater fishes.