bluuebunny/crossref_metadata_2025 huggingface dataset:
Oxidation lift-off method for layer transfer of GaAs∕AlAs-based structures
Authors: Oktyabrsky S. , Katsnelson A. , Tokranov V. , Todt R. , Yakimov M.
Published: June 2004

A method for layer transfer via attachment and release of GaAs-based components onto silicon platform in a single-step process (oxidation lift-off method) is proposed. The method involves moderate temperature (∼400°C) alloy bonding of GaAs devices with simultaneous removal of the GaAs substrate by lateral oxidation of sacrificial AlAs layer. Selectivity with respect to Al content is high enough to release the vertical cavity laser structures containing layers of AlxGa1−xAs with x=0.9. This characteristic of the oxidation process allows for the release of components and form oxide apertures during a single step. The technology can be employed for heterogeneous integration of various compound semiconductor devices with Si or other substrates.
Integrated microfluidic linking chip for scanning probe nanolithography
Authors: Ryu Kee Suk , Wang Xuefeng , Shaikh Kashan , Bullen David , Goluch Edgar , Zou Jun , Liu Chang , Mirkin Chad A.
Published: June 2004

This letter reports an architecture for a microfluidic chip that dresses (inks) multiple nanolithography tips in a high-density array in a parallel and multiplexed fashion. The microfluidic chip consists of multiple precision patterned thin-film poly(dimethylsiloxane) (PDMS) patches serving as porous inking pads. Inking chemicals are supplied from loading reservoirs to the inking pads through microfluidic channels. The gas-permeable thin PDMS membranes allow ink molecules to diffuse through while preventing bulk liquid from overflowing or evaporating. The inking chip provides high-density inking, easy loading of inks, and reduced evaporation losses. We present the fabrication process and inking of scanning probe contact printing probes and commercial nitride probes.
Topography and forest composition affecting the variability in fire severity and post-fire regeneration occurring after a large fire in the Mediterranean basin
Authors: Broncano Maria José , Retana Javier
Published: June 2004

This study relates the spatial variability in tree regeneration generated by fire with topography and pre-fire vegetation composition, and analyses how the pattern of fire severities determines post-fire regeneration of the dominant tree species (Pinus halepensis and Quercus ilex) in a large fire that occurred in north-eastern Spain in summer 1994. At the fire level, the proportion of the different fire severities in the burned area was characteristic of large fires that burn with high severity. At the level of plot, the variability of fire severity in the study site depended on two topographic characteristics: elevation and aspect. Plots burned with high fire severity were distributed at higher altitude than less severely burned plots, which were mainly distributed in south- and east-facing slopes. Fire severity also increased with Q. ilex density in the stand. The mosaic of fire severities determined both plant mortality and seedling regeneration. Mortality of stems caused by fire was very high in both species, but many Q. ilex individuals resprouted after fire. Seedling regeneration of P. halepensis showed large differences among plots in the burned area, reflecting large spatial variability due to the elevation gradient, the variation in density of adult pine trees, and the spatial variability created by fire.
Aspects of the ecology of common wombats (Vombatus ursinus) at high density on pastoral land in Victoria
Authors: Skerratt Lee F. , Skerratt John H. L. , Banks Sam , Martin Roger , Handasyde Kathrine
Published: June 2004

Free-living common wombats (Vombatus ursinus) living at high densities on pastoral land (1.9 wombats ha–1) had most of their burrows (83%) confined to a 20-m-wide strip of remnant riparian vegetation adjacent to pasture (24 burrows ha–1). The ratio of wombats to 'active' burrows (being used by wombats) was 1.0. Wombats shared burrows extensively, with a mean of 3.1 ± 0.3 (s.e.), range 2–9 wombats using each burrow (n = 37). The majority (70%) of occupied burrows contained several wombats independent of age, sex and stage of reproduction. On average, wombats used the same burrow for 3.8 consecutive nights before changing to another. Home ranges of wombats overlapped completely. Adult males had larger home ranges than females with young (7.3 ± 0.6, 6.1–8.3 ha, n = 3 versus 3.8 ± 0.5, 2.4–5.0 ha, n = 4, respectively). Distances travelled and the area used each night by wombats decreased in late winter and spring, when food was more abundant. Breeding occurred throughout the year but there was a cluster of births in summer. Lactation was associated with weight loss in females of several kilograms. Usually larger (30 kg) males that shared burrows or used burrows near (<300 m) to the burrows used by a female sired her young; however, occasionally wombats that used widely separated burrows (>700 m) bred. Adult males had a greater head length to weight ratio than adult females. Adult males generally emerged from their burrows shortly after dusk and 30 min before adult females. Ectoparasites such as ticks, mites, fleas and lice were common but the mite Sarcoptes scabiei was not found nor were there signs of sarcoptic mange in the population.
Helminth community structure in Rattus leucopus (Gray) (Muridae) from Australia, Papua New Guinea and Papua
Authors: Smales L. R. , Spratt D. M.
Published: June 2004

This study describes the helminth community in 28 Rattus leucopus, from Australia, Papua New Guinea and Papua (formerly Irian Jaya), and compares the community in Australian R. leucopus with those known from two other Australian endemics, R. sordidus and R. fuscipes. In total, 28 parasite species were found: one acanthocephalan, five cestodes, one trematode and 21 nematodes as well as two lots of unidentified spirurid nematode larvae. The diversity of helminths in R. leucopus was high but equitable; the reciprocal of Simpson's Index was 1.75. The distribution of prevalence of helminth species was not indicative of a core-satellite structure. No species occurred at a prevalence >30% and more than half the species occurred at prevalences of <10%. Only 10% of the helminth species identified were unique to R. leucopus. Helminth community structure in R. leucopus differed from that observed in R. sordidus and the community in R. fuscipes was markedly different from those in R. leucopus and R. sordidus. Determinants of the diversity of the helminth community in R. leucopus include the time intervals between the three waves of migration of Rattus spp. to Australia, biogeographic factors related to immigration and adaptive radiation of the host genus, and associated with coevolution, speciation and host switching of the helminths.
Comparison of plasma androgen profiles in green and hawksbill sea turtles inhabiting Queensland waters
Authors: Jessop Tim S. , Limpus Colin J. , Whittier Joan M.
Published: June 2004

Investigations were made into profiles of plasma androgens (combined testosterone and 5α-dihydrotestosterone) in green (Chelonia mydas) and hawksbill (Eretmochelys imbricata) turtles inhabiting waters off Queensland, Australia. First, we documented the occurrence of sex-based and ontogenetic changes in plasma androgen of immature green and hawksbill turtles occurring in wild populations. Specifically, androgen levels are increased in pubescent individuals and adults of both species and sexes. Second, we measured seasonal variation in plasma androgen profiles of adult male green and hawksbill turtles. Third, we compared plasma androgens of post-nesting green and hawksbill turtles. As for previous studies on captive green turtles, our data indicate that wild populations of green turtles also show a prenuptial spermatogenic pattern, in which plasma androgen levels rise and peak prior to migration and courtship. However, our data from male hawksbill turtles are in contrast to this pattern and provide some evidence to suggest that a delayed phase shift may occur in this population. Unlike male green turtles, male hawksbill turtles in this study all showed signs of physiological preparation for breeding.
Australian microhylid frogs (Cophixalus and Austrochaperina): phylogeny, taxonomy, calls, distributions and breeding biology
Authors: Hoskin Conrad J.
Published: June 2004

Despite a considerable surge in herpetological research in Australia over the last couple of decades the Australian microhylid frogs (Cophixalus and Austrochaperina) remain relatively poorly known. Herein I present the results of extensive fieldwork and molecular, morphological and call analysis with the aim of resolving taxonomy, call variation and distributions, and increasing our understanding of breeding biology. Analysis of 943 base pairs of mitochondrial 16S rRNA and 12S rRNA provides a well supported phylogeny that is largely consistent with current taxonomy. Levels of divergence between species are substantial and significant phylogeographic structuring is evident in C. ornatus, C. neglectus and C. aenigma, sp. nov. The description of C. concinnus was based on a mixed collection of two species from Thornton Peak and a new species is described to resolve this. C. aenigma, sp. nov., is described from high-elevation (>750 m) rainforest across the Carbine, Thornton, Finnigan and Bakers Blue Mountain uplands, north-east Queensland. C. concinnus is redescribed as a highly distinct species restricted to rainforest and boulder fields at the summit of Thornton Peak (>1100 m). Despite protection in Daintree National Park in the Wet Tropics World Heritage Area, predictions of the impact of global warming suggest C. concinnus to be of very high conservation concern (Critically Endangered, IUCN criteria). The mating call of two species (C. mcdonaldi and C. exiguus) is described for the first time and high levels of call variation within C. ornatus, C. neglectus, C. hosmeri, C. aenigma and Austrochaperina fryi are presented. Such variation is often attributable to genetically divergent lineages, altitudinal variation and courtship; however, in some instances (particularly within C. hosmeri) the source or function of highly distinct calls at a site remains obscure. Molecular, morphological and call analyses allow the clarification of species distributions, especially in the northern mountains of the Wet Tropics. Notes are presented on the breeding biology of C. aenigma, C. bombiens, C. concinnus, C. exiguus, C. infacetus, C. mcdonaldi, C. monticola, C. neglectus, C. ornatus and C. saxatilis, which are largely consistent with previous accounts: small terrestrial clutches usually attended by a male. Courtship behaviour in C. ornatus is described and the first records of multiple clutching in Australian microhylids are presented (for C. ornatus and C. infacetus).
Retinoic acid influences anteroposterior positioning of epidermal sensory neurons and their gene expression in a developing chordate (amphioxus)
Authors: Schubert Michael , Holland Nicholas D. , Escriva Hector , Holland Linda Z. , Laudet Vincent
Published: June 2004

In developing chordates, retinoic acid (RA) signaling patterns the rostrocaudal body axis globally and affects gene expression locally in some differentiating cell populations. Here we focus on development of epidermal sensory neurons in an invertebrate chordate (amphioxus) to determine how RA signaling influences their rostrocaudal distribution and gene expression (for
AmphiCoe
, a neural precursor gene; for amphioxus
islet
and
AmphiERR
, two neural differentiation genes; and for
AmphiHox1
, -
3
, -
4
, and -
6
). Treatments with RA or an RA antagonist (BMS009) shift the distribution of developing epidermal neurons anteriorly or posteriorly, respectively. These treatments also affect gene expression patterns in the epidermal neurons, suggesting that RA levels may influence specification of neuronal subtypes. Although colinear expression of
Hox
genes is well known for the amphioxus central nervous system, we find an unexpected comparable colinearity for
AmphiHox1
, -
3
, -
4
, and -
6
in the developing epidermis; moreover, RA levels affect the anteroposterior extent of these
Hox
expression domains, suggesting that RA signaling controls a colinear
Hox
code for anteroposterior patterning of the amphioxus epidermis. Thus, in amphioxus, the developing peripheral nervous system appears to be structured by mechanisms parallel to those that structure the central nervous system. One can speculate that, during evolution, an ancestral deuterostome that structured its panepidermal nervous system with an RA-influenced
Hox
code gave rise to chordates in which this patterning mechanism persisted within the epidermal elements of the peripheral nervous system and was transferred to the neuroectoderm as the central nervous system condensed dorsally.
Notch signaling in
Drosophila
long-term memory formation
Authors: Ge Xuecai , Hannan Frances , Xie Zuolei , Feng Chunhua , Tully Tim , Zhou Haimeng , Xie Zuoping , Zhong Yi
Published: June 2004

Notch (N) is a cell surface receptor that mediates an evolutionarily ancient signaling pathway to control an extraordinarily broad spectrum of cell fates and developmental processes. To gain insights into the functions of N signaling in the adult brain, we examined the involvement of N in
Drosophila
olfactory learning and memory. Long-term memory (LTM) was disrupted by blocking N signaling in conditional mutants or by acutely induced expression of a dominant-negative N transgene. In contrast, neither learning nor early memory were affected. Furthermore, induced overexpression of a wild-type (normal) N transgene specifically enhanced LTM formation. These experiments demonstrate that N signaling contributes to LTM formation in the
Drosophila
adult brain.
Neutralizing antibody response during acute and chronic hepatitis C virus infection
Authors: Logvinoff C. , Major M. E. , Oldach D. , Heyward S. , Talal A. , Balfe P. , Feinstone S. M. , Alter H. , Rice C. M. , McKeating J. A.
Published: June 2004

Little is known about the role of Abs in determining the outcome of hepatitis C virus (HCV) infection. By using infectious retroviral pseudotypes bearing HCV glycoproteins, we measured neutralizing Ab (nAb) responses during acute and chronic HCV infection. In seven acutely infected health care workers, only two developed a nAb response that failed to associate with viral clearance. In contrast, the majority of chronically infected patients had nAbs. To determine the kinetics of strain-specific and crossreactive nAb emergence, we studied patient H, the source of the prototype genotype 1a H77 HCV strain. An early weak nAb response, specific for the autologous virus, was detected at seroconversion. However, neutralization of heterologous viruses was detected only between 33 and 111 weeks of infection. We also examined the development of nAbs in 10 chimpanzees infected with H77 clonal virus. No nAb responses were detected in three animals that cleared virus, whereas strain-specific nAbs were detected in six of the seven chronically infected animals after ≈50 weeks of infection. The delayed appearance of high titer crossreactive nAbs in chronically infected patients suggests that selective mechanism(s) may operate to prevent the appearance of these Abs during acute infection. The long-term persistence of these nAbs in chronically infected patients may regulate viral replication.
Three Power Series Techniques
Authors: Hauser Herwig
Published: June 2004

The techniques and concepts we present are flags of regular schemes and their persistence under blow‐up, the Gauss–Bruhat decomposition of the group of formal automorphisms of affine space, and coordinate‐free initial ideals. All three are used to construct and study invariants for resolution of singularities. 2000 Mathematics Subject Classification 14B05, 14E15, 32S05, 32S10, 32S45.
Representations of Ariki–Koike Algebras and Gröbner–Shirshov Bases
Authors: Kang Seok‐Jin , Lee In‐Sok , Lee Kyu‐Hwan , Oh Hyekyung
Published: June 2004

In this paper, we investigate the structure of Ariki–Koike algebras and their Specht modules using Gröbner–Shirshov basis theory and combinatorics of Young tableaux. For a multipartition λ, we find a presentation of the Specht module Sλ given by generators and relations, and determine its Gröbner–Shirshov pair. As a consequence, we obtain a linear basis of Sλ consisting of standard monomials with respect to the Gröbner–Shirshov pair. We show that this monomial basis can be canonically identified with the set of cozy tableaux of shape λ. 2000 Mathematics Subject Classification 16Gxx, 05Exx.
Finite Permutation Groups with a Transitive Minimal Normal Subgroup
Authors: Bamberg John , Praeger Cheryl E.
Published: June 2004

A finite permutation group is said to be innately transitive if it contains a transitive minimal normal subgroup. In this paper, we give a characterisation and structure theorem for the finite innately transitive groups, as well as describing those innately transitive groups which preserve a product decomposition. The class of innately transitive groups contains all primitive and quasiprimitive groups. 2000 Mathematics Subject Classification 20B05, 20B15.
Measurable Schur Multipliers and Completely Bounded Multipliers of the Fourier Algebras
Authors: Spronk Nico
Published: June 2004

Let G be a locally compact group, Lp(G) be the usual Lp‐space for 1 ⩽ p ⩽ ∞, and A(G) be the Fourier algebra of G. Our goal is to study, in a new abstract context, the completely bounded multipliers of A(G), which we denote McbA(G). We show that McbA(G) can be characterised as the ‘invariant part’ of the space of (completely) bounded normal L∞(G)‐bimodule maps on B(L2(G)), the space of bounded operators on L2(G). In doing this we develop a function‐theoretic description of the normal L∞(X, μ)‐bimodule maps on B(L2(X, μ)), which we denote by V∞(X, μ), and name the measurable Schur multipliers of (X, μ). Our approach leads to many new results, some of which generalise results hitherto known only for certain classes of groups. Those results which we develop here are a uniform approach to obtaining the functorial properties of McbA(G), and a concrete description of a standard predual of McbA(G). 2000 Mathematics Subject Classification 46L07, 43A30, 43A15, 46A32, 22D10, 22D12 (primary), 22D25, 43A20, 43A07 (secondary).
Some Extremal Contractions Between Smooth Varieties Arising From Projective Geometry
Authors: Alzati Alberto , Russo Francesco
Published: June 2004

We construct explicit examples of elementary extremal contractions, both birational and of fiber type, from smooth projective n‐dimensional varieties, with n ⩾ 4, onto smooth projective varieties, arising from classical projective geometry and defined over sufficiently small fields, not necessarily algebraically closed.

The examples considered come from particular special homaloidal and subhomaloidal linear systems, which are usually degenerations of general phenomena classically investigated by Bordiga, Severi, Todd, Room, Fano, Semple and Tyrrell and more recently by Ein and Shepherd‐Barron.

The first series of examples is associated to particular codimension 2 determinantal smooth subvarieties of Pm, with 3 ⩽ m ⩽ 5. We get another series of examples by considering special cubic hypersurfaces through some surfaces in P5, or some 3‐folds in P7 having one apparent double point. The last examples come from an intriguing birational elementary extremal contraction in dimension 6, studied by Semple and Tyrrell and fully described in the last section of the paper. 2000 Mathematics Subject Classification 14E05 (primary), 14N05 (secondary).
The effects of ultraviolet-B radiation on freshwater ecosystems of the Arctic: Influence from stratospheric ozone depletion and climate change
Authors: Perin S , Lean D RS
Published: June 2004

Depletion of stratospheric ozone, the principal atmospheric attenuator of ultraviolet-B (UVB) radiation, by man-made chemicals has raised scientific and public concern regarding the biological effects of increased UVB radiation on Earth. There is an increased awareness that existing levels of solar UV radiation have an important influence on biological and chemical processes in aquatic ecosystems. For aquatic organisms, numerous studies have shown direct detrimental effects of UVB radiation at each trophic level. Fortunately, many aquatic organisms also possess a range of photoprotective mechanisms against UV radiation toxicity. In addition to its direct impact, harmful effects of UVB radiation at a single-trophic level can cascade through the food web and indirectly affect organisms from other trophic levels. Because UV radiation photochemically reacts with humic substances and other photosensitive agents in the water, increases in solar UVB can also indirectly affect aquatic organisms through the production and (or) release of different photoproducts like biologically available nutrients and harmful reactive oxygen species. Polar aquatic ecosystems have been of particular concern, since stratospheric ozone-related UVB increases have been the greatest in these regions. With the influences of climate warming and the possibility of future volcanic eruptions, ozone losses are expected to get worse in the Arctic stratosphere, and the ozone layer recovery may not follow the slow decline of industrial ozone-depleting compounds in the atmosphere. Climate warming is also expected to bring important changes in underwater ultraviolet radiation (UVR) penetration in Arctic freshwaters that would be more significant to the aquatic biota than stratospheric ozone depletion.Key words: Arctic, UV radiation, UVB, ozone depletion, climate change, aquatic ecosystems.
Anterior pituitary thyrotropes are multifunctional cells
Authors: Villalobos Carlos , Núñez Lucía , García-Sancho Javier
Published: June 2004

Anterior pituitary (AP) contains some unorthodox multifunctional cells that store and secrete two different AP hormones (polyhormonal cells) and/or respond to several hypothalamic-releasing hormones (HRHs; multiresponsive cells). Multifunctional cells may be involved in paradoxical secretion (secretion of a given AP hormone evoked by a noncorresponding HRH) and transdifferentiation (phenotypic switch between different mature cell types without cell division). Here we combine calcium imaging (to assess responses to the four HRHs) and multiple sequential immunoassay of the six AP hormones to perform a single-cell phenotypic study of thyrotropes in normal male and female mice. Surprisingly, most of the thyrotropes were polyhormonal, containing, in addition to thyrotropin (TSH), luteinizing hormone (40–42%) and prolactin (19–21%). Thyrotropes costoring growth hormone and/or ACTH were found only in females (24% of each type). These results suggest that costorage of the different hormones does not happen at random and that gender favors certain hormone combinations. Our results indicate that thyrotropes are a mosaic of cell phenotypes rather than a single cell type. The striking promiscuity of TSH storage should originate considerable mix-up of AP hormone secretions on stimulation of thyrotropes. However, response to thyrotropin-releasing hormone was much weaker in the polyhormonal thyrotropes than in the monohormonal ones. This would limit the appearance of paradoxical secretion under physiological conditions and suggests that timing of hormone and HRH receptor expression during the transdifferentiation process is finely and differentially regulated.
Maturation of TonEBP expression in developing rat kidney
Authors: Han Ki-Hwan , Woo Seung Kyoon , Kim Wan-Young , Park Soo-Hyun , Cha Jung-Ho , Kim Jin , Kwon H. Moo
Published: June 2004

Tonicity-responsive enhancer binding protein (TonEBP) is a transcriptional activator of the Rel family. In the renal medulla, TonEBP stimulates genes encoding proteins involved in cellular accumulation of organic osmolytes, the vasopressin-regulated urea transporters (UT-A), and heat shock protein 70. To understand the role of TonEBP in the development of urinary concentrating ability, TonEBP expression during rat kidney development was investigated. In embryonic kidneys, TonEBP immunoreactivity was detected 16 days postcoitus in the cytoplasm of the endothelial cells surrounding the medullary collecting ducts (MCD). By 20 days, TonEBP was detected in most tubular profiles in the medulla, including the loop of Henle and MCD, and interstitial cells. The intensity of TonEBP immunoreactivity was much higher in the vasa recta than the tubules. In addition, immunoreactivity was localized predominantly to the cytoplasm. On postnatal day 1, two major changes were observed. TonEBP immunoreactivity shifted to the nucleus, and the intensity of TonEBP immunoreactivity of the tubules increased dramatically. These changes were associated with an increase in TonEBP and sodium- myo-inositol cotransporter mRNA abundance. Thereafter, TonEBP expression in tubular profiles increased moderately. The adult pattern of TonEBP expression was established at postnatal day 21 coincident with full maturation of the renal medulla. Thus expression of TonEBP in developing kidneys occurred predominantly in the medulla and preceded expression of its target genes, including UT-A. These data suggest that TonEBP contributes to the development of urine-concentrating ability.
Increased blood pressure, aldosterone activity, and regional differences in renal ENaC protein during vasopressin escape
Authors: Song Jian , Hu Xinqun , Khan Osman , Tian Ying , Verbalis Joseph G. , Ecelbarger Carolyn A.
Published: June 2004

The syndrome of inappropriate antidiuretic hormone (SIADH) is associated with water retention and hyponatremia. The kidney adapts via a transient natriuresis and persistent diuresis, i.e., vasopressin escape. Previously, we showed an increase in the whole kidney abundance of aldosterone-sensitive proteins, the α- and γ (70-kDa-band)-subunits of the epithelial Na+channel (ENaC), and the thiazide-sensitive Na-Cl cotransporter (NCC) in our rat model of SIADH. Here we examine mean arterial pressure via radiotelemetry, aldosterone activity, and cortical vs. medullary ENaC subunit and 11β-hydroxysteroid dehydrogenase type 2 (11β-HSD-2) protein abundances in escape. Eighteen male Sprague-Dawley rats (300 g) were sham operated ( n = 6) or infused with desmopressin (dDAVP; n = 12, a V2receptor-selective analog of AVP). After 4 days, one-half of the rats receiving dDAVP were switched to a liquid diet, i.e., water loaded (WL) for 5–7 additional days. The WL rats had a sustained increase in urine volume and blood pressure (122 vs. 104 mmHg, P < 0.03, at 7 days). Urine and plasma aldosterone levels were increased in the WL group to 844 and 1,658% of the dDAVP group, respectively. NCC and α- and γ-ENaC (70-kDa band) were increased significantly in the WL group (relative to dDAVP), only in the cortex. β- and γ-ENaC (85-kDa band) were increased significantly by dDAVP in cortex and medulla relative to control. 11β-HSD-2 was increased by dDAVP in the cortex and not significantly affected by water loading. These changes may serve to attenuate Na+losses and ameliorate hyponatremia in vasopressin escape.
β1-Integrins in the primary cilium of MDCK cells potentiate fibronectin-induced Ca2+signaling
Authors: Praetorius H. A. , Praetorius J. , Nielsen S. , Frokiaer J. , Spring K. R.
Published: June 2004

Because β1-integrin is involved in sensing of fluid flow rate in endothelial cells, a function that in Madin-Darby canine kidney (MDCK) cells is confined to the primary cilium, we hypothesized β1-integrin to be an important part of the primary ciliary mechanosensory apparatus in MDCK cells. We observed that β1-integrin, α3-integrin, and perhaps α5-integrin were localized to the primary cilium of MDCK cells by combining lectin and immunofluorescence confocal microscopy. β1-Integrin was also colocalized with tubulin to the primary cilia of the rat renal collecting ducts, as well as to the cilia of proximal tubules and thick ascending limbs. Immunogold-electron microscopy confirmed the presence of β1-integrin on primary cilia of MDCK cells and rat collecting ducts. Intracellular Ca2+levels, monitored by fluorescence microscopy on fluo 4-loaded MDCK cells, significantly increased on addition of fibronectin, a β1-integrin ligand, to mature MDCK cells with an IC50of 0.02 mg/l. In immature, nonciliated cells or in deciliated mature cells, the IC50was 0.40 mg/l. Blocking the fibronectin-binding sites of β1-integrin with RGD peptide prevented the Ca2+signal. Cross-linking of β1-integrins by Sambucus nigra agglutinin produced a Ca2+response similar to the addition of fibronectin. Furthermore, the fibronectin-induced response was not dependent on flow or a flow-induced Ca2+response. Finally, the flow-induced Ca2+response was not prevented by the fibronectin-induced signal. Although β1-integrin on the primary cilium greatly potentiates the fibronectin-induced Ca2+signaling in MDCK cells, the flow-dependent Ca2+signal is not mediated through activation of β1-integrin.
EGFR-independent activation of p38 MAPK and EGFR-dependent activation of ERK1/2 are required for ROS-induced renal cell death
Authors: Dong Jing , Ramachandiran Sampath , Tikoo Kulbhushan , Jia Zhe , Lau Serrine S. , Monks Terrence J.
Published: June 2004

2,3,5-Tris-(glutathion- S-yl)hydroquinone (TGHQ), a reactive metabolite of the nephrotoxicant hydroquinone, induces the ROS-dependent activation of MAPKs, followed by histone H3 phosphorylation and oncotic cell death in renal proximal tubule epithelial cells (LLC-PK1). Cell death and histone H3 phosphorylation are attenuated by pharmacological inhibition of p38 MAPK or ERK1/2 pathways. Because TGHQ, but not epidermal growth factor (EGF), induces histone H3 phosphorylation and cell death in LLC-PK1cells, we hypothesized that there are differences in the mechanisms by which TGHQ and EGF induce activation of the EGF receptor (EGFR). We therefore compared the relative ability of TGHQ, H2O2, and EGF to activate EGFR and MAPKs and found that p38 MAPK activation is EGFR independent, whereas ERK1/2 activation occurs mainly through EGFR activation. TGHQ, H2O2, and EGF induce different EGFR tyrosine phosphorylation profiles that likely influence the subsequent differential kinetics of MAPK activation. We next transfected LLC-PK1cells with a dominant negative p38 MAPK-expressing plasmid (pcDNA3-DNp38). TGHQ failed to induce phosphorylation of p38 MAPK and its substrate, MK-2, in pcDNA3-DNp38-transfected cells, indicating loss of function of p38 MAPK. In untransfected, pcDNA3 or pcDNA3-p38 (native)-transfected LLC-PK1cells, Hsp27 was intensively phosphorylated after TGHQ treatment, whereas in pcDNA3-DNp38-transfected cells, TGHQ failed to induce Hsp27 phosphorylation. Thus EGFR-independent p38 MAPK and EGFR-dependent ERK1/2 activation by TGHQ lead to the activation of two downstream signaling factors, i.e., histone H3 and Hsp27 phosphorylation, which have in common the potential ability to remodel chromatin.
Grp78 is essential for 11-deoxy-16,16-dimethyl PGE2-mediated cytoprotection in renal epithelial cells
Authors: Jia Zhe , Person Maria D. , Dong Jing , Shen Jianjm , Hensley Sean C. , Stevens James L. , Monks Terrence J. , Lau Serrine S.
Published: June 2004

11-Deoxy-16,16-dimethyl PGE2(DDM-PGE2) protects renal proximal tubule epithelial cells (LLC-PK1) against the toxicity induced by 2,3,5- tris(glutathion- S-yl)hydroquinone (TGHQ), a potent nephrotoxic and nephrocarcinogenic metabolite of hydroquinone. We have now determined the ability of DDM-PGE2to protect against other renal toxicants and report that DDM-PGE2only protects against oncotic cell death, induced by H2O2, iodoacetamide, and TGHQ, but not against apoptotic cell death induced by cisplatin, mercuric chloride, or tumor necrosis factor-α. DDM-PGE2-mediated cytoprotection is associated with the upregulation of at least five proteins, including the major endoplasmic reticulum (ER) chaperone glucose-regulated protein 78 (Grp78). To elucidate the role of Grp78 in oncotic cell death, we used LLC-PK1cells in which induction of grp78 expression was disrupted by stable expression of an antisense grp78 RNA (pkASgrp78). As anticipated, DDM-PGE2failed to induce Grp78 in pkASgrp78 cells, with a concomitant inability to provide cytoprotection. In contrast, DDM-PGE2induced Grp78 and afforded cytoprotection against H2O2, iodoacetamide, and TGHQ in empty vector transfected cells (pkNEO). These data suggest that Grp78 plays an essential role in DDM-PGE2-mediated cytoprotection. Moreover, TGHQ-induced p38 MAPK activation is disrupted under conditions of a compromised ER stress response in pkASgrp78 cells, which likely contributes to the loss of cytoprotection. Finally, using two-dimensional gel electrophoresis coupled to matrix-assisted laser desorption/ionization time-of-flight mass spectroscopy, we found that DDM-PGE2induced several proteins in pkNEO cells, but not in pkASgrp78 cells, including retinol-binding protein, myosin light chain, and heat shock protein 27. The findings suggest that additional proteins may act in concert with Grp78 during DDM-PGE2-mediated cytoprotection against oncotic cell death.
Kinetic analysis of cardiac transcriptome regulation during chronic high-fat diet in dogs
Authors: Philip-Couderc Pierre , Smih Fatima , Hall John E. , Pathak Atul , Roncalli Jérome , Harmancey Romain , Massabuau Pierre , Galinier Michel , Verwaerde Patrick , Senard Jean-Michel , Rouet Philippe
Published: June 2004

In the present study, we investigated, using custom dog cDNA arrays, the time course of transcriptional changes in the left ventricle of dogs fed a normal diet or a high-fat diet (HFD) for 9–24 wk. Array hybridizations were performed with complex probes representing mRNAs expressed in left ventricles from obese hypertensive and lean control dogs. We identified 63 differentially expressed genes, and expression of 17 of 20 randomly chosen genes was confirmed by real-time PCR. Transcripts were categorized into groups involved in metabolism, cell signaling, tissue remodeling, ionic regulation, cell proliferation, and protein synthesis. Hierarchical clustering indicated that the pattern of coregulated genes depends on duration of the HFD, suggesting that HFD-induced obesity hypertension is associated with continuous cardiac transcriptome adaptation despite stability of both body weight and blood pressure. GenMAPP analysis of the data pointed out the crucial importance of the ventricle TGF-β pathway. Our results suggest that this system may be involved in molecular remodeling during HFD and in changes observed in the transcription profile, reflecting functional and morphological abnormalities that arise during prolonged HFD. These results also suggest some novel regulatory pathways for cardiac adaptation to obesity.
Mild impairment of motor nerve repair in mice lacking PTP-BL tyrosine phosphatase activity
Authors: Wansink Derick G. , Peters Wilma , Schaafsma Iris , Sutmuller Roger P. M. , Oerlemans Frank , Adema Gosse J. , Wieringa Bé , van der Zee Catharina E. E. M. , Hendriks Wiljan
Published: June 2004

Mouse PTP-BL is a large, nontransmembrane protein tyrosine phosphatase of unclear physiological function that consists of a KIND domain, a FERM domain, five PDZ domains, and a COOH-terminal catalytic PTP domain. PTP-BL and its human ortholog PTP-BAS have been proposed to play a role in the regulation of microfilament dynamics, cytokinesis, apoptosis, and neurite outgrowth. To investigate the biological function of PTP-BL enzyme activity, we have generated mice that lack the PTP-BL PTP moiety. These PTP-BLΔP/ΔPmice are viable and fertile and do not present overt morphological alterations. Although PTP-BL is expressed in most hematopoietic cell lineages, no alterations of thymocyte development in PTP-BLΔP/ΔPmice could be detected. Sciatic nerve lesioning revealed that sensory nerve recovery is unaltered in these mice. In contrast, a very mild but significant impairment of motor nerve repair was observed. Our findings exclude an essential role for PTP-BL as a phosphotyrosine phosphatase and rather are in line with a role as scaffolding or anchoring molecule.
Messianic Ecumenism: Missiological Reflections
Authors: Jongeneel Jan
Published: June 2004

In this article the author pleads for a new type of ecumenism. We are known with the Christian ecumenical movement. K.-J. Kuschel has proposed an Abrahamic ecumenism of Judaism, Christianity and Islam. Jongeneel comes with a plea for a messianic ecumenism, a going together of all people striving for a universal breaking away from sin and crime to resist the de facto demonic pressure of those who want to subjugate fellow humans and to strive for a brighter future on six continents.
Who, with whom, about what? Exploring the Landscape of Inter-Religious Dialogue
Authors: Kuester Volker
Published: June 2004

In this article the author presents a new way of approaching people adhering to other religions. After a discussion of the meetings and relationships between Christianity, Judaism and Islam, and those between Christianity and Hinduism, Buddhism or African religion he tries to create a new space between inclusivism and exclusivism. He calls this space the 'third space'. It is an 'in-between', a meeting place for the dialogue of life, a place of wisdom for the dialogue of the mind, and a place of spiritual experiences for the dialogue of the heart. Theologically speaking it is a space of transcendence that for each religion is filled in a distinct way.
Ecclesiogenesis: The Patchwork of New Religious Communities in Brazil
Authors: Troch Lieve
Published: June 2004

This article presents a survey of the latest developments in the religious world of Brazil. The author discusses the newest developments in the Roman Catholic Church moving from an orientation on the liberation theology towards an approach directed to a more individual perception of faith. Furthermore she pays attention to Candomblé, the religion of many blacks in Brazil, the roots of which can be traced to Africa, to New Age and to the Pentecostal churches. A very interesting phenomenon is the impact of the scholars. From the religious point of view Brazil is a very interesting country because of the ecclesiogenesis taking place in the country, an emergence of new churches and religious movements.
Mithradates' Antidote – A Pharmacological Ghost
Authors: Totelin Laurence
Published: June 2004

Two kinds of sources are available to the historian to reconstruct the first centuries of the history of Mithradates' antidote: biographical information on Mithradates' interests in medicine, and a series of recipes. In this paper I argue that we cannot reconstruct the original recipe of Mithridatium from our existing sources. Instead, I examine how the Romans remodelled the history of the King's death and used the royal name to create a "Roman" drug. This drug enjoyed a huge popularity in the first centuries of the Roman Empire. An Emperor, Marcus Aurelius, consumed it as well as members of the upper class; and many highly literate physicians recommended it notwithstanding the medical sect they were belonging to. With all its expensive ingredients, and its claim to work as a panacea, Mithridatium responded to a real demand in a Roman Empire at its commercial and political apogee.
Anatomy of a Dispute: Leonardo, Pacioli and Scientific Courtly Entertainment in Renaissance Milan
Authors: Azzolini Monica
Published: June 2004

Historians have recently paid increasing attention to the role of the disputation in Italian universities and humanist circles. By contrast, the role of disputations as forms of entertainment at fifteenth-century Italian courts has been somewhat overlooked. In this article, the Milanese "scientific duel" (a courtly disputation) described in Luca Pacioli's De divina proportione is taken as a vantage point for the study of the dynamics of scientific patronage and social advancement as reflected in Renaissance courtly disputes. Pacioli names Leonardo da Vinci as one of the participants in the Milanese dispute. In this paper I argue that Leonardo's Paragone and Pacioli's De divina proportione are likewise the outcome of the Milanese "scientific duel." By challenging the traditional hierarchy of the arts, they both exemplify the dynamics of social and intellectual promotion of mathematicians and artists in the privileged setting of Renaissance courts, where courtly patronage could subvert the traditional disciplinary rankings.
Missiology as Global Conversation of (Contextual) Theologies
Authors: Kim Kirsteen
Published: June 2004

Missiology and contextual theology are related but not equivalent. Missiology arose from the study of mission activity in the former mission fields of Africa, Asia and Latin America but has come to be understood as the study of the mission of God in the whole world in which the church participates. Global and cross-cultural perspectives are essential to missiology and these challenge all theological parochialism. There is a danger that contextual theology degenerates into relativism, but in mission all theologies are challenged to recognize their own contextuality and at the same time their common Christian confession. Grounded in an understanding of missio Dei that includes a creation theology of the Holy Spirit, missiology can and should affirm contextual theologizing while encouraging and facilitating theologians from different contexts to pursue a global conversation. "Conversation" is preferred over "dialogue" because there are many partners from around the world, various means of conversing, and widely varying access to social power among the participants.
The Future of Mission in the World Council of Churches: The Dialogue between Lesslie Newbigin and Konrad Raiser
Authors: Goheen Michael
Published: June 2004

In this article, Michael W. Goheen summarizes and evaluates a debate between ecumenical pioneer Lesslie Newbigin and former WCC general secretary Konrad Raiser. Raiser exemplifies a trinitarian approach to ecumenism and mission that recognizes the universal presence of the Holy Spirit among all peoples and religions, and so would cease to have a Christocentric focus. For Newbigin, while a trinitarian approach to ecumenism and mission is of paramount importance, an abandonment of the centrality and universality of Jesus Christ is something that cannot be abandoned. In the end, says Goheen, the differences between Raiser and Newbigin are differences revolving around the meaning of Jesus Christ and his atoning work on the cross.
Transcriptional activation of hTERT through the NF-κB pathway in HTLV-I–transformed cells
Authors: Sinha-Datta Uma , Horikawa Izumi , Michishita Eriko , Datta Abhik , Sigler-Nicot Janitzia C. , Brown Megan , Kazanji Mirdad , Barrett J. Carl , Nicot Christophe
Published: June 2004

In immortal cells, the existence of a mechanism for the maintenance of telomere length is critical. In most cases this is achieved by the reactivation of telomerase, a cellular reverse transcriptase that prevents telomere shortening. Here we report that the telomerase gene (hTERT) promoter is up-regulated during transmission of human T-cell lymphotropic virus type-I (HTLV-I) to primary T cells in vitro and in ex vivo adult T-cell leukemia/lymphoma (ATLL) samples, but not asymptomatic carriers. Although Tax impaired induction of human telomerase reverse transcriptase (hTERT) mRNA in response to mitogenic stimulation, transduction of Tax into primary lymphocytes was sufficient to activate and maintain telomerase expression and telomere length when cultured in the absence of any exogenous stimulation. Transient transfection assays revealed that Tax stimulates the hTERT promoter through the nuclear factor κB (NF-κB) pathway. Consistently, Tax mutants inactive for NF-κB activation could not activate the hTERT or sustain telomere length in transduced primary lymphocytes. Analysis of the hTERT promoter occupancy in vivo using chromatin immunoprecipitation assays suggested that an increased binding of c-Myc and Sp1 is involved in the NF-κB–mediated activation of the hTERT promoter. This study establishes the role of Tax in regulation of telomerase expression, which may cooperate with other functions of Tax to promote HTLV-I–associated adult T-cell leukemia.
A novel type 2A von Willebrand factor mutation located at the last nucleotide of exon 26 (3538G>A) causes skipping of 2 nonadjacent exons
Authors: James Paula D. , O'Brien Lee A. , Hegadorn Carol A. , Notley Colleen R. P. , Sinclair Gary D. , Hough Christine , Poon Man-Chiu , Lillicrap David
Published: June 2004

In this manuscript, we describe a case of type 2A von Willebrand disease (VWD) caused by the novel heterozygous G>A transition at nucleotide 3538, which should result in the putative, nonconservative substitution of G1180R. This mutation was reproduced by site-directed mutagenesis; however, the recombinant mutant protein was efficiently secreted from cells and assembled correctly into multimers. Because the substitution is located at the last nucleotide of exon 26, the patient's platelet von Willebrand factor (VWF) mRNA was analyzed and 3 transcripts were observed: the normal transcript without the 3538G>A transition, a transcript with the in-frame deletion of exon 26, and a transcript with the in-frame deletions of exons 23 and 26. These deletion VWF cDNA constructs were created and the resulting recombinant proteins were analyzed following transfection into COS-7 cells. Cotransfection results demonstrate that the exon-skipped transcripts led to intracellular retention, and the levels of VWF antigen (VWF:Ag) produced by these constructs were as follows: del23/26<del26< G1180R≤wild type. The homozygous exon-skipped transcripts show the presence of only the lowest molecular weight multimers. The G>A transition at nucleotide (nt) 3538 does not result in the expression of the G1180R missense mutation, but rather leads to exon skipping, which is the pathogenic basis of the patient's phenotype. This is the first report of a coding region mutation resulting in the skipping of 2 nonadjacent exons. (Blood. 2004;104:2739-2745)
A computational model of human granulopoiesis to simulate the hematotoxic effects of multicycle polychemotherapy
Authors: Engel Christoph , Scholz Markus , Loeffler Markus
Published: June 2004

Moderate intensification of conventional multicycle chemotherapy has recently been shown to improve treatment results in malignant lymphomas and might prove to be beneficial also in other malignancies. However, the feasibility of such regimens is mainly limited by their granulopoietic toxicity. To identify and quantify the basic cell kinetic mechanisms of damage and stimulation caused by cytotoxic drugs and recombinant human granulocyte colony-stimulating factor (rhG-CSF), respectively, we developed a mathematical model of human granulopoiesis that allows simulation of leukocyte concentration profiles under 10 different multicycle polychemotherapy regimens with varying drug composition, dosage, and scheduling, including rhG-CSF assistance. Clinical data on leukocyte profiles were obtained from large numbers of patients treated within several multicenter trials. Simulation studies show that the leukocyte profiles of all regimens can be appropriately fitted using one single set of assumptions and parameters for the cell kinetic effects of cytotoxic drugs and rhG-CSF. Furthermore, the model can be used to explain the interindividual heterogeneity of hematotoxicity by a differential chemosensitivity, which might be useful in drug scheduling for specific risk groups. It is demonstrated that the model can be used to design and to select new drug schedules for subsequent clinical trial testing.