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  • Inorganic Chemistry  (83,671)
  • Cell & Developmental Biology  (25,032)
  • 42.73
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  • 1
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    Frontiers Media SA
    Publication Date: 2024-04-04
    Description: The Frontiers in Chemistry Editorial Office team are delighted to present the inaugural “Frontiers in Chemistry: Rising Stars” article collection, showcasing the high-quality work of internationally recognized researchers in the early stages of their independent careers. All Rising Star researchers featured within this collection were individually nominated by the Journal’s Chief Editors in recognition of their potential to influence the future directions in their respective fields. The work presented here highlights the diversity of research performed across the entire breadth of the chemical sciences, and presents advances in theory, experiment and methodology with applications to compelling problems. This Editorial features the corresponding author(s) of each paper published within this important collection, ordered by section alphabetically, highlighting them as the great researchers of the future. The Frontiers in Chemistry Editorial Office team would like to thank each researcher who contributed their work to this collection. We would also like to personally thank our Chief Editors for their exemplary leadership of this article collection; their strong support and passion for this important, community-driven collection has ensured its success and global impact.
    Keywords: Green and Sustainable Chemistry ; Analytical Chemistry ; Theoretical and Computational Chemistry ; Polymer Chemistry ; Medicinal and Pharmaceutical Chemistry ; Organic Chemistry ; Nanoscience ; Catalysis and Photocatalysis ; Supramolecular Chemistry ; Electrochemistry ; Inorganic Chemistry ; Chemical Biology ; thema EDItEUR::P Mathematics and Science::PD Science: general issues
    Language: English
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  • 2
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    American Association for the Advancement of Science (AAAS)
    In: Science
    Publication Date: 2017-02-10
    Description: Author: Jake Yeston
    Keywords: Inorganic Chemistry
    Print ISSN: 0036-8075
    Electronic ISSN: 1095-9203
    Topics: Biology , Chemistry and Pharmacology , Geosciences , Computer Science , Medicine , Natural Sciences in General , Physics
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  • 3
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    American Association for the Advancement of Science (AAAS)
    In: Science
    Publication Date: 2017-01-27
    Description: Author: Jake Yeston
    Keywords: Inorganic Chemistry
    Print ISSN: 0036-8075
    Electronic ISSN: 1095-9203
    Topics: Biology , Chemistry and Pharmacology , Geosciences , Computer Science , Medicine , Natural Sciences in General , Physics
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  • 4
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    American Association for the Advancement of Science (AAAS)
    In: Science
    Publication Date: 2017-01-27
    Description: Polynitrogens have the potential for ultrahigh-performing explosives or propellants because singly or doubly bonded polynitrogens can decompose to triply bonded dinitrogen (N2) with an extraordinarily large energy release. The large energy content and relatively low activation energy toward decomposition makes the synthesis of a stable polynitrogen allotrope an extraordinary challenge. Many elements exist in different forms (allotropes)—for example, carbon can exist as graphite, diamond, buckyballs, or graphene. However, no stable neutral allotropes are known for nitrogen, and only two stable homonuclear polynitrogen ions had been isolated until now—namely, the N3− anion (1) and the N5+ cation (2). On page 374 of this issue, Zhang et al. (3) report the synthesis and characterization of the first stable salt of the cyclo-N5− anion, only the third stable homonuclear polynitrogen ion ever isolated. Author: Karl O. Christe
    Keywords: Inorganic Chemistry
    Print ISSN: 0036-8075
    Electronic ISSN: 1095-9203
    Topics: Biology , Chemistry and Pharmacology , Geosciences , Computer Science , Medicine , Natural Sciences in General , Physics
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  • 5
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    American Association for the Advancement of Science (AAAS)
    In: Science
    Publication Date: 2016-09-09
    Description: Author: Jake Yeston
    Keywords: Inorganic Chemistry
    Print ISSN: 0036-8075
    Electronic ISSN: 1095-9203
    Topics: Biology , Chemistry and Pharmacology , Geosciences , Computer Science , Medicine , Natural Sciences in General , Physics
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  • 6
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    American Association for the Advancement of Science (AAAS)
    In: Science
    Publication Date: 2016-11-11
    Description: Author: Jake Yeston
    Keywords: Inorganic Chemistry
    Print ISSN: 0036-8075
    Electronic ISSN: 1095-9203
    Topics: Biology , Chemistry and Pharmacology , Geosciences , Computer Science , Medicine , Natural Sciences in General , Physics
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  • 7
    Publication Date: 2016-06-09
    Description: The anatomy, functional morphology and evolutionary ecology of the Viviparidae, and the subfamily Bellamyinae in particular, are incompletely known. Partly as a result, genealogical relationships within the family remain poorly understood. Because of this lack in knowledge, few informed hypotheses exist on ancestral states, how differences in body plans between the subfamilies evolved, and how the peculiar biogeographic distribution patterns of viviparids have arisen. Here we document the anatomy, morphology, life history and systematics of Cipangopaludina japonica, a Japanese species that has been introduced into North America, to resolve taxonomic confusion and to improve our understanding of how form and function are related in bellamyines. Anatomical and histological examinations demonstrate marked differences between C. japonica and other bellamyines in the radula, salivary gland, kidney, nerve ring and reproductive organs. Substantial differences also exist between male and female body organization, but conchological differences between sexes in semi-landmark morphometric analyses are limited. The volume of the brood pouch of females, and hence body and shell size, appear to be good predictors of reproductive success, and the species’ ecological versatility may relate to high fecundity and the ability to alternate between feeding modes. Comparing our observations on C. japonica with other viviparids and basal architaenioglossa, we identify several persistent misinterpretations in the literature on how form and function are related in viviparids, not in the least as to female reproductive anatomy. Our reinterpretations improve understanding of the evolution of Viviparidae and its subfamilies, and hopefully will allow future workers to isolate key traits that shaped the evolution of viviparids at the taxonomic levels of their interest for more detailed studies.
    Keywords: basal Architaenioglossa ; Bellamya ; fecundity ; geometric morphometrics ; histology ; reproductive anatomy ; sexual dimorphism ; 42.73
    Repository Name: National Museum of Natural History, Netherlands
    Type: Article / Letter to the editor
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  • 8
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    In:  Various articles (2305-2562) vol.56 (2015) nr.3 p.585
    Publication Date: 2015-12-30
    Description: Twenty-five species of Pectinoidea (24 Propeamussiidae, 1 Cyclochlamydidae) are herein listed from the Mozambique Channel, northwestern and southern Madagascar, and northeastern South Africa. New species: Propeamussium rosadoi, Parvamussium catillus, Parvamussium kilburni, Parvamussium puillandrei, Parvamussium strongae, Cyclopecten cassiculus, Cyclopecten kantori, Cyclochlamys bacachorda. New synonym: Amussium sewelli Knudsen, 1967 = Propeamussium watsoni (E.A. Smith, 1885). New records for the Mozambique Channel and northwestern Madagascar: Propeamussium andamanicum, Propeamussium arabicum, Propeamussium caducum, Propeamussium jeffreysii, Propeamussium sibogai, Propeamussium watsoni, Parvamussium formosum, Parvamussium scitulum, Parvamussium torresi, Parvamussium vesiculatum, Cyclopecten kapalae, Similipecten eous. New records for southern Madagascar: Propeamussium jeffreysii, Propeamussium sibogai, Propeamussium watsoni, Parvamussium formosum, Parvamussium scitulum, Parvamussium thyrideum, Parvamussium vesiculatum, Parvamussium vidalense, Cyclopecten kapalae, Similipecten eous. New record for South Africa: Propeamussium jeffreysii, Parvamussium formosum, Parvamussium scitulum, Cyclopecten horridus, Similipecten eous.
    Keywords: Pectinoidea ; Mollusca ; Propeamussiidae ; Cyclochlamydidae ; SW Indian Ocean ; new taxa ; new synonym ; new records ; 42.73
    Repository Name: National Museum of Natural History, Netherlands
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  • 9
    Publication Date: 2014-11-05
    Description: Kimberleytrachia Köhler, 2011 is a genus of camaenid land snail endemic to the Western Australian Kimberley region. It comprises twelve previously recognised species, all of which occur within the high precipitation zone along the north-western coast between the Admiralty Gulf and King Sound and within less than about 50 km distance from the coast. By evaluating the variation in shell and genital anatomy as well as the differentiation in the mitochondrial markers 16S and COI, we assess the monophyly of Kimberleytrachia with respect to other camaenid genera from north-western Australia. In addition, we newly describe six species (K. jacksonensis n. sp., K. leopardus n. sp., K. nelsonensis n. sp., K. serrata n. sp., K. setosa n. sp. and K. silvaepluvialis n. sp.) based on comparative morphology and mitochondrial DNA differentiation. We found that a rather smooth, weakly elevated shell and, in particular, the complex penial anatomy are key morphological characteristics of Kimberleytrachia. Its constituent species are differentiated by a combination of shell and genital features and their morphological disparity appears to be more pronounced when species occur in sympatry. While island species are usually narrowly endemic to one or a few islands, the mainland species have much larger distributional ranges. One new species from the Maret and Berthier Islands, Bonaparte Archipelago, is phylogenetically and morphologically so distinct from Kimberleytrachia that it is recognized as a new monotypic genus, Succochlea n. gen.
    Keywords: genetic distances ; Helicoidea ; mitochondrial DNA ; new species ; Stylommatophora ; 42.73 ; 42.64
    Repository Name: National Museum of Natural History, Netherlands
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  • 10
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    In:  Scripta Geologica (03757587) vol.133 (2006) p.19
    Publication Date: 2007-01-09
    Description: The mollusc fauna of the Miocene Pebas Formation of Peruvian and Colombian Amazonia contains at least 158 mollusc species, 73 of which are introduced as new; 13 are described in open nomenclature. Four genera are introduced (the cochliopid genera Feliconcha and Glabertryonia, and the corbulid genera Pachyrotunda and Concentricavalva) and a nomen novum is introduced for one genus (Longosoma). A neotype is designated for Liosoma glabra Conrad, 1874a. The Pebas fauna is taxonomically dominated by two families, viz. the Cochliopidae (86 species; 54%) and Corbulidae (23 species; 15%). The fauna can be characterised as aquatic (155 species; 98%), endemic (114 species; 72%) and extinct (only four species are extant). Many of the families represented by a few species in the Pebas fauna include important ecological groups, such as indicators of marine influence (e.g., Nassariidae, one species), terrestrial settings (e.g., Acavidae, one species) and stagnant to marginally agitated freshwaters (e.g., Planorbidae, four species). Only seven species (4%) representing undisputedly elevated salinities were found, whereas 31 species (20%) are undisputed restricted to freshwater biotopes. Only three (2%) terrestrial gastropod species are known. The Pebas system experienced profuse radiations of molluscs that led to an overwhelmingly endemic fauna, typical of a long-lived lake environment. Several extant genera, which nowadays live outside Amazonia, may have originated within the Pebas system. The stratigraphic continuity of species and line ages, at least for the late Early-early Late Miocene interval (c. 18-9 Ma), indicates that lakes continuously occupied the system and never were entirely replaced by rivers or the sea. The rare occurrence of marine taxa indicates that the system was at sealevel and occasionally experienced marine incursions.
    Keywords: Mollusca ; systematics ; Pebas Formation ; Miocene ; western Amazonia ; 42.73 ; 38.22
    Repository Name: National Museum of Natural History, Netherlands
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  • 11
    Publication Date: 2010-12-12
    Description: Gulella (s.l.) johannae n. sp. is described from a few forest localities in the Tzaneen District, Limpopo Province, South Africa. It is characterized by a cylindrical, costulate shell with an almost entire peristome and a four-fold apertural dentition consisting of a prominent angular lamella (delimiting an only here discontinuous peristome), a mid-labral denticle, a left basal denticle, and a mid-columellar process. The shell is somewhat similar to that of G. johannesburgensis, but is consistently larger and more slender and has more whorls, while at the same time the apertural dentition is better developed; the almost uninterrupted peristome also appears to be a signifi cant character. This new taxon most likely is a restrictedrange endemic on the eastern flanks of the northern Drakensberg escarpment. Numerical data of a lot of material identified and mostly also published as G. johannesburgensis show that probably not all specimens belong to this taxon so that more than one species may be involved here.
    Keywords: Mollusca ; Gastropoda ; Pulmonata ; Streptaxidae ; Gulella, Gulella johannesburgensis ; taxonomy ; Drakensberg range ; South Africa ; 42.73
    Repository Name: National Museum of Natural History, Netherlands
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  • 12
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    In:  Scripta Geologica (03757587) vol.133 (2006) p.419
    Publication Date: 2007-01-09
    Description: Thirteen species of fossil molluscs are reported from the Solimões Formation of western Brazilian Amazonia. Based on mammalian chronology of the Solimões Formation and radiometric ages reported from coeval deposits in adjacent Peru, the age of the fauna is established as Late Miocene. The fauna includes five prosobranch gastropod species, seven pearly freshwater mussel species and one sphaeriid bivalve species. The supposed presence of Pachydon (Corbulidae: Bivalvia) in these deposits is rejected; Pachydon acreanum, whose status has long been uncertain, is transferred to the unionoid genus Callonaia. The Solimões mollusc fauna is entirely composed of obligate freshwater taxa, resembling species-poor modern Amazonian fluvial faunas. The presence of the fauna in outcrops covering large parts of western Amazonia indicates that by that time the preceding Pebas fauna (dominated by corbulid bivalves and cochliopid snails) must have been extinguished.
    Keywords: Mollusca ; western Amazonia ; Miocene ; Solimões Formation. ; 38.22 ; 42.73
    Repository Name: National Museum of Natural History, Netherlands
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  • 13
    Publication Date: 2007-01-09
    Description: Miocene deposits in western Amazonia and adjacent areas of South America harbour a diverse suite of endemic corbulid bivalves, commonly referred to as Pachydontinae, that show a wide variety of morphologies. Especially in the Miocene Pebas Formation (Peru, Colombia and Brazil), this group diversified spectacularly. Since these corbulids (a cosmopolitan marine and perimarine bivalve family) occur with freshwater taxa and yield isotope signals strongly indicative of freshwater settings, the success of this group in inland basins of Miocene northwestern South America is surprising. In this paper it is argued that a combination of adaptations to fluid bottom substrates, common dysoxia and high predation intensities explains their abundance, their morphological diversity and the paucity of freshwater bivalve groups, such as Sphaeriidae, Corbiculidae and Unionoidea.
    Keywords: Corbulidae ; Pachydontinae ; Miocene ; Amazonia ; evolution ; adaptation ; 42.73 ; 38.22
    Repository Name: National Museum of Natural History, Netherlands
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  • 14
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    In:  Scripta Geologica (03757587) vol.133 (2006) p.439
    Publication Date: 2007-01-15
    Description: Between c. 23 and 8 Ma, western Amazonia was occupied by the vast Pebas long-lived lake/wetland system. The Pebas system had a variety of influences over the evolution of Miocene and modern Amazonian biota; it formed a barrier for the exchange of terrestrial biota, a pathway for the transition of marine biota into freshwater Amazonian environments, and formed the stage of remarkable radiations of endemic molluscs and ostracods. The lithological variation of the Pebas Formation has furthermore enhanced edaphic heterogeneity in western Amazonia, sustaining present-day high terrestrial diversity in the region.
    Keywords: Miocene ; Amazonia ; biogeography ; biodiversity ; Mollusca ; 42.73 ; 38.22
    Repository Name: National Museum of Natural History, Netherlands
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  • 15
    Publication Date: 2007-01-09
    Description: The Miocene Pebas Formation from the section Santa Rosa de Pichana (Loreto, Peru) was investigated using a combination of analyses of sedimentary facies, molluscan communities and taphonomy, and stable isotopes of both entire shells and growth bands in bivalves. Three sequences, comprising a succession of transgressive, maximum flooding and regressive/prograding intervals, are documented. Molluscs are most common in the transgressive/highstand intervals and are almost absent in regressive/prograding intervals. The fauna is dominated by endemic Pebasian species, such as Pachydon and Dyris spp. The nature of the deposits as well as the availability of oxygen varied in a predictable way within each of the sequences and determined the nature of the assemblages. Highest diversity was reached in the late transgressive phase before the development of dysoxia that was widespread during the late highstand and early regressive/prograding phase. The mollusc and isotope data show no indications of elevated salinities, in contrast to ichnofossils found in the section. This discrepancy is interpreted to result either from temporal separation of the ichnofossils and the mollusc fossils or from evolution beyond usual ecological tolerances of taxa that produced these ichnofossils into freshwater settings.
    Keywords: Miocene ; Amazonia ; palaeoecology ; sedimentology ; stable isotopes ; 38.22 ; 42.73
    Repository Name: National Museum of Natural History, Netherlands
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  • 16
    Publication Date: 2007-01-15
    Description: A biozonation based on molluscs is proposed for Miocene deposits of western Amazonia (Peru, Colombia and Brazil), commonly referred to as the Pebas Formation. The new zonation refines existing pollen zonations and provides a key for the quick assessment of the stratigraphic position of Neogene deposits in the field. The regional distribution of twelve mollusc zones reveals a structuring of geological units around the broad Iquitos-Araracuara anteclise. The structure of the subsurface appears to have been a major factor in the determination of present-day second and lower order river courses in the study area. Based on this work a biostratigraphic framework for Miocene deposits of western Amazonia, including fossiliferous deposits from adjacent basins (Putumayo, Llanos and Magdalena basins in Colombia), is proposed.
    Keywords: stratigraphy ; Mollusca ; Miocene ; western Amazonia ; Pebas Formation ; 42.73 ; 38.22
    Repository Name: National Museum of Natural History, Netherlands
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  • 17
    Publication Date: 2014-11-07
    Description: Doto uva Marcus, 1955 is a nudibranch species recorded from the Brazilian and Chilean coast. In spite of its wide distribution, D. uva has been described only superficially, mainly as to the pattern of its coloration, external morphology, radular teeth and reproductive system. Here we substantially extend this description, paying special attention to the morphology, anatomy and histology of the digestive and reproductive system. Furthermore, new data on the morphology of the central nervous system and its cell types are given, and finally, the egg mass is described. On the basis of these data, we consider the Doto specimens described from Chile conspecific with those from Brazil.
    Keywords: Opisthobranchia ; Nudibranchia ; Doto ; Histology ; Morphology ; Chilean coast ; 42.73
    Repository Name: National Museum of Natural History, Netherlands
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  • 18
    Publication Date: 2007-01-09
    Description: The Miocene Pebas system was a huge (〉 1 million km2) system of long-lived lakes and wetlands that occupied most of western Amazonia between c. 23 and 8 Ma. Remarkable endemic radiations of molluscs and ostracods occurred in the Pebas system. The continuity of many of the endemic lineages between c. 17 and 9 Ma shows that the system was never fully replaced by fluvial or marine settings. Many of the endemic invertebrate groups developed an unusual range of morphologies that reflect adaptation to specific ecological stresses provided by the Pebas system, such as chemical stress, common dysoxia and high predation pressure. Mollusc diversity increased especially during the Middle Miocene. The Pebas system provided pathways for mobile marine organisms to transfer into freshwater biotopes, and at the same time obstructed exchange of terrestrial biota between the tropical Andes and the Guyana region. Short-lived, lowland aquatic corridors over northern shield regions and through the Ecuadorian Andean region almost certainly existed. The Pebas system was terminated just before the establishment of the modern Amazon system (slightly before 8 Ma), possibly coinciding with a single, wide ranging marine incursion into lowland Amazonia. With the termination of the Pebas system, the endemic mollusc fauna became largely extinct. The termination of the Pebas system provided large tracts of land for the establishment and development of terrestrial biota in western Amazonia. Subsequent diversification in lowland Amazonia has been enhanced by the edaphic heterogeneity of the Pebas Formation deposits.
    Keywords: Miocene ; Amazonia ; molluscs ; landscape evolution ; Pebas Formation ; 42.73 ; 38.22
    Repository Name: National Museum of Natural History, Netherlands
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  • 19
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    In:  Scripta Geologica (03757587) vol.130 (2005) p.1
    Publication Date: 2007-01-12
    Description: Tonnoidean gastropods in K. Martin’s and other collections in the Nationaal Natuurhistorisch Museum, Leiden (and a few other minor collections) are reidentified and classified. The resulting fauna of 99 species is very similar to that of the Indo-West Pacific today, 70% of species still inhabiting the Indonesian region. Species endemic to the Miocene and Pliocene rocks of Indonesia are Bursa sangirana sp. nov., and two new (unnamed) species similar to Bursina ignobilis (Beu); Cassis depressior Martin and C. preangerensis Martin; Cypraecassis denseplicata (Martin) and an unnamed species of Cypraecassis; Sconsia martini van Regteren Altena and S. pulchra Pannekoek; Echinophoria vandervlerki Martin (possibly a synonym of E. wyvillei (Watson)); Phalium menkrawitense Beets and P. rembangense (Martin); Distorsio denseplicata van Regteren Altena and D. djunggranganensis (Martin); Biplex magnifica (Martin), B. pamotanensis (Martin) and B. perliberalis (Beets); Cymatium (Monoplex) gembacanum (Martin) (?=C. exaratum (Reeve)), C. rembangense (Wanner & Hahn), and C. tjaringinense (Martin); Cymatium (Ranularia) pseudopyrum (Martin) and an unnamed species of C. (Ranularia); Cymatium (Septa) dharmai sp. nov.; Sassia (Cymatiella) fennemai (Martin), S. (C.) menkrawitensis (Beets) and an unnamed species of S. (Cymatiella); Eudolium erbi (Haanstra & Spiker), E. errabundum (Beets) and E. pamotanense (Martin); Malea(?) papuana (Beets); and Sconsodolium (gen. nov.) rembangense (Pannekoek). These 30 species (30% of the recorded fauna), and the generic groups Sconsia, Sconsodolium and Sassia (Cymatiella), are all “additional” tropical western Pacific taxa that became extinct before the present day (Sconsia and Sassia (Cymatiella) only locally), as a result of Pleistocene climate change. Species previously included in Bufonaria Schumacher prove to belong in two distinct genera; species closely related to “Bursa” nobilis have a subcentral (rather than mid-left edge) opercular nucleus and are reclassified in Bursina Oyama. “Sconsia” rembangensis Pannekoek is an elongate, axially ridged cassid with a coarsely plicate inner lip; the new genus Sconsodolium is proposed for it. Galeodea bituminata (Martin) and G. carolimartini Beets are both earlier names for the western Pacific species (originally described in the Recent fauna) previously known as G. echinophorella Habe. Eudolium javanum (Martin) is an earlier name for the Indo-West Pacific species (originally described in the Recent fauna) previously known as E. pyriforme (G.B. Sowerby 3rd), whereas E. bituminata Martin is a synonym of the near-cosmopolitan species E. bairdii (Verrill & Smith). Ranella spinosa var. granosa Martin is either an earlier name for the western Pacific species (originally described in the Recent fauna) previously known as Bufonaria perelegans Beu, or a closely similar, but distinct, species. Purpura bantamensis Martin, Cassis tegalensis Martin, Dolium losariense Martin, and Tritonium verbeeki Boettger are all synonyms of Cymatium (Linatella) cingulatum (Lamarck).
    Keywords: Gastropoda ; Tonnoidea ; Neogene ; Indonesia ; taxonomy ; biogeography ; 42.73
    Repository Name: National Museum of Natural History, Netherlands
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  • 20
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    In:  Contributions to Zoology (13834517) vol.74, 1/2 (2005) p.27
    Publication Date: 2014-11-07
    Description: After a massive mortality of the dominant species (the clam Mesodesma mactroides) occurred in 1995, changes in the intertidal community in sandy beaches of Argentina were monitored. Eight sampling stations were established in a 40 km open stretch and samples were taken every October each year up to 2001. Biomass, density, size frequency distribution and mean growth rates for the most abundant species were analyzed. During the mortality event, only the benthic stages of M. mactroides were affected, their total mean biomass diminishing from 1,399 g to 2 g per running meter beach. Post-mortality recruitment was normal and the growth rates for the youngest cohorts were similar to those previously reported. After a two years’ lag, the wedge clam Donax hanleyanus replaced M. mactroides as the dominant species, increasing from 6.0 g/m up to 24.3 g/m. However, dominance replacement did not restore the productivity of the intertidal macrobenthic assemblage and, despite the increment of D. hanleyanus stocks, the community total biomass remained 〈 1% of the pre-mortality levels. Since 1998 on, M. mactroides and D. hanleyanus showed several peaks in abundance. Disturbance, mainly due to non-regulated fisheries, has been delaying the community recovery. Taking into account the interactions among species and human activities, the present individual resourcebased management should be replaced by an integrated systembased management program including both conservation and tourism requirements.
    Keywords: Surf clams ; Mesodesma mactroides ; Donax hanleyanus ; sandy beaches ; benthos ; Argentina ; species interactions ; 42.73
    Repository Name: National Museum of Natural History, Netherlands
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  • 21
    Publication Date: 2015-06-03
    Description: Twenty-two epitoniid species that live associated with various hard coral species are described. Three genera, viz. Epidendrium gen. nov., Epifungium gen. nov., and Surrepifungium gen. nov., and ten species are introduced as new to science, viz. Epidendrium aureum spec. nov., E. sordidum spec. nov., Epifungium adgranulosa spec. nov., E. adgravis spec. nov., E. adscabra spec. nov., E. marki spec. nov., E. nielsi spec. nov., E. pseudolochi spec. nov., E. pseudotwilae spec. nov., Surrepifungium patamakanthini spec. nov., and ‘Epitonium’ crassicostatum spec. nov. and ‘E.’ graviarmatum spec. nov. Although their identities as separate gene pools are convincingly demonstrated by molecular data, some of these species cannot be identified unequivocally on the basis of conchological characters alone. The shell shape and sculpture are only partially diagnostic because of interspecifically overlapping character states. In most of these cases, the operculum, jaw structure, radula, spawn and/or the habitat do reveal the identity. Most of these species are associated with only one or a restricted number of coral host species and have large ranges, similar to those of their hosts.
    Keywords: Indo-Pacific ; parasites ; coral reefs ; coral/mollusc associations ; Epitoniidae ; Epitonium ; Epidendrium ; Epifungium ; Surrepifungium ; new species ; new genera ; Scleractinia ; Fungiidae ; Fungia ; 42.73
    Repository Name: National Museum of Natural History, Netherlands
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  • 22
    Publication Date: 2007-01-18
    Description: On the basis of new and published palaeontological and stratigraphical data, the qualitative and quantitative variations in the Barremian-early Albian ammonite fauna of Colombia have been documented and analyzed. The position adopted here is that in the early Barremian the Andean Province became replaced by the Caribbean Subprovince in Colombia. The Caribbean Subprovince became separated as an independent unit from the Andean Province on the generic level (Buergliceras, Pedioceras), but especially on the species level. In the middle/upper Aptian many new endemic genera and subgenera appeared; Juandurhamiceras, Neodeshayesites, Laqueoceras, Zambranoites, Riedelites and Pseudoptychoceras. Besides, many endemic middle Aptian species of other, non-endemic genera appeared. Beginning from the middle Aptian the Caribbean area was a separate biogeographic enitity with the rank of Province; the Colombian region is considered to be the core area of the Caribbean Province.
    Keywords: palaeobiogeography ; Early Cretaceous ; ammonites ; Colombia ; 38.22 ; 42.73
    Repository Name: National Museum of Natural History, Netherlands
    Type: Article / Letter to the editor
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  • 23
    facet.materialart.
    Unknown
    In:  Scripta Geologica (03757587) vol.128 (2004) p.183
    Publication Date: 2007-01-18
    Description: Forty seven species (among them fourteen new that are listed below) of the following ammonite genera of the families Deshayesitidae Stoyanow, Oppeliidae Douvillé, Desmoceratidae Zittel, and Silesitidae Hyatt are described. Neodeshayesites includes the new species N. buergli, N. striatus, N. biplicatus, N. longicostatus, N. multicostatus, N. euglyphoides and N. tuberculatus. Dufrenoyia includes the new species D. renzi. Pseudohaploceras includes the new species P. gerhardti, P. yucaense, P.? yeseraense and P. simile. Melchiorites includes the new species M. colombianus. Zuercherella includes the new species Z. etayosernai. Other species belong to the genera Juandurhamiceras, Aconeceras, Pseudosaynella, Valdedorsella, Puzosia, Carloscaceresiceras, Kennicottia and Miyakoceras.
    Keywords: ammonites ; Barremian ; Aptian ; Albian ; Colombia ; 38.22 ; 42.73
    Repository Name: National Museum of Natural History, Netherlands
    Type: Article / Letter to the editor
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  • 24
    facet.materialart.
    Unknown
    In:  Scripta Geologica (03757587) vol.128 (2004) p.182
    Publication Date: 2007-01-18
    Description: Thirty seven species and subspecies of ammonites of the families Ancyloceratidae Gill, 1871, and Heteroceratidae Spath, 1922, are described. The following new taxa are described; Crioceratites (Paracrioceras) leyvaensis, C. (P.) royogomezi, C. (P.) cabreraensis, Pedioceras multicostatum, Pseudocrioceras guanense, Kutatissites creutzbergi, K. densecostatus compactus, K. etayosernai, K. grandis, K.? galanensis, Ammonitoceras galanense, A. giganteum, Hamiticeras ventrotuberculatum, H. longum, Hemihoplites (Matheronites) ridzewskyi sachicaensis, Colchidites riosuarezi, C. pseudovulanensis, C. guanensis and C. striatosulcatus. Moreover, one new genus, Laqueoceras gen. nov., with the type species L. laqueus sp. nov., is proposed.
    Keywords: heteromorphic ammonites ; Barremian ; Aptian ; Colombia ; 38.22 ; 42.73
    Repository Name: National Museum of Natural History, Netherlands
    Type: Article / Letter to the editor
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  • 25
    facet.materialart.
    Unknown
    In:  Zoologische Mededelingen (00240672) vol.78, 18-28 (2004) p.417
    Publication Date: 2007-01-18
    Description: The history and current taxonomic status of 62 nominal taxa are revised that have been associated in the literature with the subgenus Tholachatina Bequaert, 1950, of genus Archachatina Albers, 1850, and the genus Cochlitoma Férussac, 1821, in the land snail family Achatinidae Swainson, 1840. Tangible, reliable characters have been found in the detailed features of the reproductive anatomy in this family. The results of comparative anatomical study convincingly reflect phylogeny in contrast to the comparative study of only the shell characters. This latter more strongly reflects the effects of the intrinsically variable environment over time. In the present study, both sets of characters are needed to refine identification. Change, and therefore speciation, is shown in the reproductive system through anatomical differences that may develop in the functional interrelationships of the two integral reproductive systems of hermaphroditism. Limited adjustment to anatomical change over time has established for each genus a typical, characteristic reproductive anatomical pattern or configuration. Because this pattern has a basically high degree of physical stability within a population, it becomes an identifying character for the genus, and more restrictedly so for the species. Two new genera (Bruggenina and Brownisca) and two new species (Cochlitoma kilburni and C. wigleyi) are described on the basis of distinctive anatomical characters. The genus Cochlitoma sensu Pilsbry (1904) is resurrected and redescribed. It contains most of the southern African achatinid species. Bequaert’s subgenus Tholachatina (1950) of West African genus Archachatina is invalid. The genus Archachatina Albers, 1850, has no endemic species in southern Africa.
    Keywords: Mollusca ; Gastropoda ; Pulmonata ; Achatinidae ; biogeography ; taxonomy ; genital anatomy ; Southern Africa ; East Africa ; 42.73
    Repository Name: National Museum of Natural History, Netherlands
    Type: Article / Letter to the editor
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  • 26
    Publication Date: 2007-01-18
    Description: The variability in the dimensions of the shell, and some changes in suture line, sculpture, whorl section and mode of coiling in the late ontogenetic stages, have in some cases no taxonomic significance for the recognition of genera and higher taxa of Cretaceous heteromorph ammonites. In many cases, such phenomena are due to intraspecific variation or variation within a genus. The intrageneric variations of some Cretaceous heteromorphs are discussed in detail in the light of new, rich Colombian material. In relation to these problems in systematics, some questions on the systematics of the superfamily Ancyloceratoidea Gill are considered.
    Keywords: ammonites ; heteromorphs ; dimorphism ; systematics ; Cretaceous ; 38.22 ; 42.73
    Repository Name: National Museum of Natural History, Netherlands
    Type: Article / Letter to the editor
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  • 27
    Publication Date: 2007-01-18
    Description: Seventy nine species and subspecies of the following ammonite genera and subgenera of the families Douvilleiceratidae Parona & Bonarelli, Acanthohoplitidae Stoyanow, and Parahoplitidae Spath are described from the study area. Fourteen species are new; Cheloniceras rectangulatum, Ch. guanense, Epicheloniceras wiedmanni, E. douvillei, E. bradleyiformis, Vectisites (Zambranoites) nodosus, V. (Z.) etayosernai, V. (Z.) obscurus, V. (Z.) grandis, Gargasiceras subpulcher, Colombiceras formosum, Protacanthoplites originalis, Riedelites latecostatus, R. microtuberculatus.
    Keywords: ammonites ; systematics ; Aptian ; Albian ; Colombia ; 38.22 ; 42.73
    Repository Name: National Museum of Natural History, Netherlands
    Type: Article / Letter to the editor
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  • 28
    facet.materialart.
    Unknown
    In:  Scripta Geologica (03757587) vol.128 (2004) p.1
    Publication Date: 2007-01-18
    Keywords: Early Cretaceous ; ammonites ; Colombia ; 38.20 ; 42.73
    Repository Name: National Museum of Natural History, Netherlands
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  • 29
    Electronic Resource
    Electronic Resource
    New York, NY [u.a.] : Wiley-Blackwell
    Journal of Cellular Physiology 177 (1998), S. 377-386 
    ISSN: 0021-9541
    Keywords: Life and Medical Sciences ; Cell & Developmental Biology
    Source: Wiley InterScience Backfile Collection 1832-2000
    Topics: Biology , Medicine
    Notes: Apoptosis in cells of different lineages is restrained by survival signals which depend upon cell-to-cell communication. The aim of this study was to determine whether colonic cells deprived of crypt ambient are doomed to die prior to their normal chronological demise. Apoptosis was studied in rat whole colonic tissue, in isolated intact crypts, and in colonic cell populations collected from the crypt axis at different stages of proliferation and differentiation. In a number of experiments, cell harvest was performed in the presence of either a tetrapeptide (YVAD-CMK) inhibitor of interleukin-1β-converting enzyme (ICE), or tyrphostin A25, a protein tyrosine kinase inhibitor, or sodium-orthovanadate, a phosphatase inhibitor. DNA fragmentation was assessed by electrophoretic and nonisotopic-labeling procedures. The ultrastructure of colonic tissue specimens and isolated cells was examined by transmission electron microscopy. Apoptosis in whole colonic tissue and in isolated crypts was confined predominantly to cells resident in the upper crypt regions. In contrast, extensive apoptotic death was observed in isolated colonic cells, irrespective of their developmental stage and positional hierarchy within the crypt continuum at harvest time. An apoptotic gradient, however, was evident. Exposure to YVAD-CMK resulted in a marked decrease in the number of apoptotic cells. Treatment with tyrphostin A25 caused a sharp rise in the apoptotic index; conversely, vanadate significantly impeded apoptosis. Cumulatively, these results indicate that disordered intercellular communication provokes unscheduled ICE-mediated apoptosis of colonocytes, and that local signals along the crypt continuum control both the reprieve from death and the timely demise of distinct colonic cell populations. Attenuation of tyrosine phosphorylation may be a contributory event in the acquisition of the apoptotic phenotype. J. Cell. Physiol. 177:377-386, 1998. © 1998 Wiley-Liss, Inc.
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  • 30
    Electronic Resource
    Electronic Resource
    New York, NY [u.a.] : Wiley-Blackwell
    Journal of Cellular Physiology 177 (1998), S. 518-524 
    ISSN: 0021-9541
    Keywords: Life and Medical Sciences ; Cell & Developmental Biology
    Source: Wiley InterScience Backfile Collection 1832-2000
    Topics: Biology , Medicine
    Notes: No abstract.
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  • 31
    Electronic Resource
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    New York, NY [u.a.] : Wiley-Blackwell
    Journal of Cellular Physiology 177 (1998), S. 525-534 
    ISSN: 0021-9541
    Keywords: Life and Medical Sciences ; Cell & Developmental Biology
    Source: Wiley InterScience Backfile Collection 1832-2000
    Topics: Biology , Medicine
    Notes: No abstract.
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  • 32
    Electronic Resource
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    New York, NY [u.a.] : Wiley-Blackwell
    Journal of Cellular Physiology 177 (1998), S. 575-584 
    ISSN: 0021-9541
    Keywords: Life and Medical Sciences ; Cell & Developmental Biology
    Source: Wiley InterScience Backfile Collection 1832-2000
    Topics: Biology , Medicine
    Notes: The role of hsp27 as an inhibitor of actin polymerization was considered in the context of the actin cytoskeleton and its relationship with focal adhesion formation. The aim of this study was to evaluate the potential effects of hsp27 on focal adhesion formation as a relevant biological consequence of actin stress fiber formation. When hsp27 was overexpressed in stably transfected cells, cell attachment was delayed and recovery of disrupted stress fibers and focal adhesions was limited. In ROS 17/2.8 cells, heat shock caused the reversible disruption of stress fibers and focal adhesions. The loss of stress fibers and focal adhesions was associated with reduced phosphotyrosine on the focal adhesion kinase (FAK). Microinjection of recombinant 6-His hsp27 and phosphorylated 6-His hsp27 was used to demonstrate that nonphosphorylated hsp27 prevented the recovery of stress fibers and focal adhesions. These results provide in vivo evidence that hsp27 acts as an inhibitor of actin polymerization that can alter cellular interactions with extracellular environments by perturbation of stress fibers, and subsequently focal adhesions. J Cell Physiol 177:575-584, 1998. © 1998 Wiley-Liss, Inc.
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  • 33
    ISSN: 0021-9541
    Keywords: Life and Medical Sciences ; Cell & Developmental Biology
    Source: Wiley InterScience Backfile Collection 1832-2000
    Topics: Biology , Medicine
    Notes: Hepatocytes entrapped in collagen gel and cultured in serum-free conditions survived longer than cells cultured on plastic (5 days vs. 3 weeks), showed fewer signs of early cell senescence (no increase in c-fos oncoprotein expression), and maintained the expression of differentiated hepatic metabolic functions over a longer period of time. Cells cultured in collagen gels retained their ability to respond to hormones. The insulin-stimulated glycogen synthesis rate remained fairly constant during 18 days in culture (between 5.4 ± 0.37 and 9 ± 2.7 nmol glucose/h/μg DNA). Collagen-cultured hepatocytes recovered glycogen stores to levels similar to those found in liver, or in hepatocytes isolated from fed rats. Urea synthesis from ammonia remained stable for more than 2 weeks (average value, 23 ± 4 nmol urea/h/μg DNA). The rate of albumin synthesis in collagen-entrapped cells was maintained above the day-1 level during 18 days in culture. Cells showed high levels of glutathione (GSH) (1,278 ± 152 pmol/μg DNA). Biotransformation activities CYP4501A1, CYP4502A2, CYP4502B1, and CYP4503A1 remained fairly stable in collagen-cultured hepatocytes. CYP4502E1 and CYP4502C11 decreased but were still measurable after 18 days. After 4 days in culture, GST activity returned to levels observed in isolated hepatocytes. In contrast with plastic cultures, cells responded to CYP450 inducers (methylcholanthrene for CYP4501A1, CYP4501A2, and gluthatione-transferase, and ethanol for CYP4502E1) for more than 2 weeks. CYP4501A1, CYP4501A2, and glutathione-transferase A2 (GST A2) induction was preceded by an increase in specific mRNA, while the effects on CYP4502E1 seemed to be at a posttranslational level. Analysis of the expression of relevant hepatic genes by reverse Northern and semiquantitative reverse transcriptase-polymerase chain reaction (RT-PCR) revealed that culturing hepatocytes in collagen gels results in a sustained higher expression of key liver transcription factor genes DBP, C/EBP-α and -β, and HNF-1 and -4, as well as specific liver enzyme genes (phosphoenol pyryvate carboxykinase, and carbamoylphosphate-synthetase I). J Cell Physiol 177:553-562, 1998. © 1998 Wiley-Liss, Inc.
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  • 34
    Electronic Resource
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    New York, NY [u.a.] : Wiley-Blackwell
    Journal of Cellular Physiology 177 (1998), S. 535-552 
    ISSN: 0021-9541
    Keywords: Life and Medical Sciences ; Cell & Developmental Biology
    Source: Wiley InterScience Backfile Collection 1832-2000
    Topics: Biology , Medicine
    Notes: The viral Crk oncogene (v-Crk) is known to induce sarcomas in chicken and its cellular homologs c-Crk I, c-Crk II, and Crk-like (CRKL) have been implicated in many signal transduction events. These include cell differentiation, cell migration, and the induced nonresponsiveness of T-cells to stimulation of the T-cell receptor (TCR), a state known as anergy. CRKL is also the most prominent substrate of the Bcr-Abl oncoprotein which causes human chronic myelogenous leukemias (CML). The modular composition of the Crk family adapters which largely consist of Src homology (SH2 and SH3) domains has prompted an intensive search for physiological and pathological upstream and downstream signalling partners which selectively bind to these adapters. Upstream proteins include various receptors and large multisite docking proteins, while several protein kinases and guanine nucleotide release proteins (GNRPs) have been suggested to function downstream of c-Crk and CRKL. Most Crk/CRKL SH2- and SH3-binding proteins contain several docking sites with considerable sequence similarity. Thus the binding requirements of Crk/CRKL SH2 and SH3 domains are now well defined, providing a basis for the design of small inhibitory molecules to block the function of these adapter proteins. The enzymatic cascades activated through Crk family adapters are only partially known, but stress kinases (SAPKs/JNKs) and the GTPase Rap1, as well as the B-Raf isoform of the Raf protein kinases, are affected in some systems. Several yet unidentified, highly selective Crk interacting proteins detectable in specific cell types remain to be studied. More detailed analyses of the enzymatic activities triggered through Crk-type adapters will also be crucial to fully define the signalling pathways controlled by this protein family. J Cell Physiol 177:535-552, 1998. © 1998 Wiley-Liss, Inc.
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  • 35
    ISSN: 0021-9541
    Keywords: Life and Medical Sciences ; Cell & Developmental Biology
    Source: Wiley InterScience Backfile Collection 1832-2000
    Topics: Biology , Medicine
    Notes: We have previously described a specific, saturable receptor for rat collagenase-3 in the rat osteosarcoma cell line, UMR 106-01. Binding of rat collagenase-3 to this receptor is coupled to the internalization and eventual degradation of the enzyme and correlates with observed extracellular levels of the enzyme. In this study we have shown that decreased binding, internalization, and degradation of 125I-rat collagenase-3 were observed in cells after 24 h of parathyroid hormone treatment; these activities returned to control values after 48 h and were increased substantially (twice control levels) after 96 h of treatment with the hormone. Subcellular fractionation studies to identify the route of uptake and degradation of collagenase-3 localized intracellular accumulation of 125I-rat collagenase-3 initially in Golgi-associated lysosomes and later in secondary lysosomes. Maximal lysosomal accumulation of the radiolabel and stimulation of general lysosomal activity occurred after 72 h of parathyroid hormone treatment. Preventing fusion of endosomes with lysosomes (by temperature shift, colchicine, or monensin) resulted in no internalized 125I-collagenase-3 in either lysosomal fraction. Treatment of UMR cells with the above agents or ammonium chloride decreased excretion of 125I-labeled degradation products of collagenase-3. These experiments demonstrated that degradation of collagenase-3 required receptor-mediated endocytosis and sequential processing by endosomes and lysosomes. Thus, parathyroid hormone regulates the expression and synthesis of collagenase-3 as well as the abundance and functioning of the collagenase-3 receptor and the intracellular degradation of its ligand. The coordinate changes in the secretion of collagenase-3 and expression of the receptor determine the net abundance of the enzyme in the extracellular space. J Cell Physiol 177:563-574, 1998. © 1998 Wiley-Liss, Inc.
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  • 36
    Electronic Resource
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    New York, NY [u.a.] : Wiley-Blackwell
    Journal of Cellular Physiology 177 (1998), S. 585-592 
    ISSN: 0021-9541
    Keywords: Life and Medical Sciences ; Cell & Developmental Biology
    Source: Wiley InterScience Backfile Collection 1832-2000
    Topics: Biology , Medicine
    Notes: The effect of metabolic inhibitors on nontransferrin bound iron transport by K562 cells was investigated. Incubation with 1 μM rotenone, 10 μM antimycin, or 0.5 mM 2,4-dinitrophenol effectively reduced ATP levels by ∼50%. Both the rate and extent of Fe+3 uptake were impaired in ATP-depleted cells, which display a reduced Vmax for uptake. K562 cell ferrireductase activity was also lowered by metabolic inhibitors, suggesting that the apparent energy requirements for transport reside in the reduction of Fe+3 to Fe+2. However, ATP depletion was found to inhibit the rate and extent of Fe+2 uptake as well. Thus, the transbilayer passage of Fe+2 and/or Fe+3 appears to be an energy-requiring process. These features possibly reflect properties of the transport mechanism associated with a recently identified K562 cell transport protein, called SFT for “Stimulator of Fe Transport,” since exogenous expression of its activity is also affected by ATP depletion. J Cell Physiol 177:585-592, 1998. © 1998 Wiley-Liss, Inc.
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  • 37
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    New York, NY [u.a.] : Wiley-Blackwell
    Journal of Cellular Physiology 177 (1998), S. 593-605 
    ISSN: 0021-9541
    Keywords: Life and Medical Sciences ; Cell & Developmental Biology
    Source: Wiley InterScience Backfile Collection 1832-2000
    Topics: Biology , Medicine
    Notes: Clusterin (ApoJ) is an extracellular glycoprotein expressed during processes of tissue differentiation and regression that involve programmed cell death (apoptosis). Increased clusterin expression has also been found in tumors, however, the mechanism underlying this induction is not known. Apoptotic processes in tumors could be responsible for clusterin gene activation. Alternatively, oncogenic mutations could modulate signal transduction, thereby inducing the gene. We examined the response of the rat clusterin gene to two oncogenes, Ha-ras and c-myc, in transfected Rat1 fibroblasts. While c-myc overexpression did not modify clusterin gene activity, the Ha-ras oncogene produced a seven to tenfold repression of clusterin mRNA; this down-regulation was also observed in the presence of c-myc. Since no induction of the clusterin gene was observed by the two oncogenes, we tested the alternative mechanism involving apoptosis. Growth factor withdrawal induced apoptosis, as shown by DNA degradation and micronuclei formation in the floating cells. Concomittantly we observed a three to tenfold increase in the amount of clusterin mRNA in the adhering cells of Rat1 and the c-myc transformed cell lines, and a weaker induction in the Ha-ras transformed cell line. On the basis of our results, we suggest that clusterin gene induction in the vital cells is produced by signaling molecules that are generated by the apoptotic cells. We conclude that apoptotic processes, not oncogenic mutations, are responsible for increased clusterin expression in tumors. J Cell Physiol 177:593-605, 1998. © 1998 Wiley-Liss, Inc.
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  • 38
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    Journal of Cellular Physiology 177 (1998), S. 618-627 
    ISSN: 0021-9541
    Keywords: Life and Medical Sciences ; Cell & Developmental Biology
    Source: Wiley InterScience Backfile Collection 1832-2000
    Topics: Biology , Medicine
    Notes: We previously reported that the enterocytic differentiation of human colonic Caco-2 cells correlated with down-regulation of fibronectin (FN) and laminin (LN), two extracellular matrix components interacting with cell surface integrin receptors. We now investigated whether Caco-2 cell differentiation was associated with alterations in integrin signaling with special interest in the expression and activity of focal adhesion kinase (FAK) and mitogen-activated protein (MAP) kinase. The differentiation of Caco-2 cells was associated with: (1) down-regulation of β1 integrin expression at the mRNA and protein levels; (2) increased FAK expression together with decreased FAK autophosphorylation; (3) decreased FAK's ability to associate with PI3-kinase and pp60c-src; and (4) increased MAP kinase expression along with decreased MAP activity. In addition, we show that FAK and MAP kinase belong to distinct integrin signaling pathways and that both pathways remain functional during Caco-2 cell differentiation since the coating of differentiating cells on FN and LN but not on polylysine increased the tyrosine phosphorylation of FAK and of its endogenous substrate paxillin, and stimulated MAP kinase activity. In conclusion, our results provide evidence that FAK and MAP kinase, two signaling molecules activated independently by β1 integrins in Caco-2 cells, undergo alterations of both expression and activity during the enterocytic differentiation of this cell line. J Cell Physiol 177:618-627, 1998. © 1998 Wiley-Liss, Inc.
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  • 39
    ISSN: 0021-9541
    Keywords: Life and Medical Sciences ; Cell & Developmental Biology
    Source: Wiley InterScience Backfile Collection 1832-2000
    Topics: Biology , Medicine
    Notes: Salivary glands contain two major epithelial cell types: acinar cells which produce the primary salivary secretion, including amylase, and ductal cells which reabsorb electrolytes but also secrete kallikrein. Here we investigated salivary acinar cell differentiation in vitro using the activity of the salivary amylase and tissue kallikrein promoters as markers of acinar cell and ductal cell differentiation, respectively. Each of the promoter sequences was cloned into a replication-deficient adenoviral vector containing the luciferase reporter gene. Previous studies showed that a human submandibular gland cell line (HSG) differentiated into acinar cells when cultured on a reconstituted basement membrane matrix (Matrigel). The luciferase activity of the amylase promoter vector (AdAMY-luc) was low in HSG cells cultured on plastic, where they grow as an epithelial monolayer. The promoter activity increased approximately tenfold when HSG cells were cultured on Matrigel and developed an acinar phenotype. Under the same conditions, the luciferase activity of the kallikrein promoter (AdKALL-luc) was not induced. Because HSG cells demonstrate acinar cell morphology, but not amylase gene expression, when cultured on laminin-1, certain soluble components of Matrigel were tested for their ability to induce the amylase promoter during in vitro differentiation of acinar cells. We find that epidermal growth factor (EGF) and transforming growth factor-alpha (TGF-α), which are present in the basement membrane, and hepatocyte growth factor (HGF) increase activity of the amylase promoter. Other basement membrane-derived growth factors such as TGF-β, basic fibroblast growth factor (bFGF), and platelet-derived growth factor (PGDF), as well as tumor necrosis factor (TNF-α), keratinocyte growth factor (KGH), nerve growth factor (NGF) and interferon gamma (IFN-γ) were inactive. This system will be further exploited to study the mechanisms by which extracellular matrix molecules and growth factors regulate salivary acinar cell differentiation. J Cell Physiol 177:628-635, 1998. Published 1998 Wiley-Liss, Inc.
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  • 40
    ISSN: 0021-9541
    Keywords: Life and Medical Sciences ; Cell & Developmental Biology
    Source: Wiley InterScience Backfile Collection 1832-2000
    Topics: Biology , Medicine
    Notes: The role of HSP27 in cell growth and resistance to stress was investigated using murine fibrosarcoma L929 cells (normally devoid of constitutively expressed small HSPs) and human osteoblast-like SaOS-2 cells stably transfected with a human hsp27 expression vector. Our data showed that our L929 cells were more resistant to oxidative stress than generally observed for this line. Production of HSP27 in these cells led to a marked decrease in growth rate associated with a series of phenotypical changes, including cell spreading, cellular and nuclear hypertrophy, development of an irregular outline, and a tremendous accumulation of actin stress fibers. By contrast, none of these changes was observable in SaOS-2/hsp27 transfectants overexpressing the protein product. Together, these observations are consistent with a cause-to-effect cascade relationship between increased (or induced) HSP27 expression, changes in cytoskeletal organization, and decreased growth. On the other hand, whereas the transfection of the hsp27 gene increased the cell resistance to heat in both cell lines, only in SaOS-2 cells was this associated with protection to the cytotoxic action of tumor necrosis factor-alpha (TNF-α) and etoposide. Unexpectedly, L929/hsp27 transfectants exhibited an increased sensitivity to both agents and also to H2O2. These data thus imply that different mechanisms are involved in the cell resistance to heat shock and to the cytotoxic action of TNF-α, etoposide, and H2O2. They also plead against the simple view that overexpression of a phosphorylatable HSP27 would necessarily be beneficial in terms of increased cell resistance to any type of stress. Our data further indicate that the role of HSP27 in cellular resistance to stress and in cell proliferation involves different targets and that the ultimate result of its interference with these processes depends on the intracellular context in which the protein is expressed. J Cell Physiol 177:606-617, 1998. © 1998 Wiley-Liss, Inc.
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  • 41
    ISSN: 0021-9541
    Keywords: Life and Medical Sciences ; Cell & Developmental Biology
    Source: Wiley InterScience Backfile Collection 1832-2000
    Topics: Biology , Medicine
    Notes: Using an expression cloning approach, we identified and cloned a novel intracellular protein produced by osteoclasts that indirectly induces osteoclast formation and bone resorption, termed OSF. Conditioned media from 293 cells transiently transfected with the 0.9 kb OSF cDNA clone stimulated osteoclast-like cell formation in both human and murine marrow cultures in the presence or absence 10-9 M 1,25-dihydroxyvitamin D3. In addition, conditioned media from 293 cells transfected with the OSF cDNA clone enhanced the stimulatory effects of 1,25-(OH)2D3 on bone resorption in the fetal rat long bone assay. In situ hybridization studies using antisense oligomers showed expression of OSF mRNA in highly purified osteoclast-like cells from human giant cell tumors of the bone. Northern blot analysis demonstrated ubiquitous expression of a 1.3 kb mRNA that encodes OSF in multiple human tissues. Sequence analysis showed the OSF cDNA encoded a 28 kD peptide that contains a c-Src homology 3 domain (SH3) and ankyrin repeats, suggesting that it was not a secreted protein, but that it was potentially involved in cell signaling. Consistent with these data, immunoblot analysis using rabbit antisera against recombinant OSF demonstrated OSF expression in cell lysates but not in the culture media. Furthermore, recombinant OSF had a high affinity for c-Src, an important regulator of osteoclast activity. Taken together, these data suggest that OSF is a novel intracellular protein that indirectly enhances osteoclast formation and osteoclastic bone resorption through the cellular signal transduction cascade, possibly through its interactions with c-Src or other Src-related proteins. J Cell Physiol 177:636-645, 1998. © 1998 Wiley-Liss, Inc.
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  • 42
    ISSN: 0021-9541
    Keywords: Life and Medical Sciences ; Cell & Developmental Biology
    Source: Wiley InterScience Backfile Collection 1832-2000
    Topics: Biology , Medicine
    Notes: The addition of dexamethasone (dex) to human fibroblast cultures has been found to elicit enhanced proliferation. This enhancement is manifested by an increase in the initial growth rate, saturation density, and proliferative life span of WI-38 fibroblast cultures grown in the presence of dex. We examined the acute effects of dex on a number of growth-related genes in WI-38 cells. Our results show a decrease in the level of the cyclin-dependent kinase inhibitor p21Waf1/Cip1/Sdi1 in response to dex. In addition, the level of the insulin-like growth factor type 1 receptor (IGF-1R) is increased in dex-treated cells. These changes are correlated with changes in the activity of the p21Waf1/Cip1/Sdi1 and IGF-1R promoters. The results presented in this report suggest that dex may delay growth arrest in response to contact inhibition, as well as during cellular senescence. Thus, dex may act at multiple levels to enhance cellular proliferation in WI-38 cells: first, to decrease the level of an inhibitor of cell-cycle progression, and second, to increase the sensitivity of WI-38 cells to the proliferative effects of IGF-1. These acute effects may cooperate with other, as yet uncharacterized effects, to result in the enhanced proliferation seen in the presence of dex. J. Cell. Physiol. 177:396-401, 1998. © 1998 Wiley-Liss, Inc.
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  • 43
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    Journal of Cellular Physiology 177 (1998), S. 402-410 
    ISSN: 0021-9541
    Keywords: Life and Medical Sciences ; Cell & Developmental Biology
    Source: Wiley InterScience Backfile Collection 1832-2000
    Topics: Biology , Medicine
    Notes: Potassium (K+) conductances are known to be involved in cell proliferation of a number of nonexcitable cell types. The nature of the mechanism by which K+ channel inhibition reduces cell proliferation has remained elusive despite intensive search. We investigated whether such a phenomenon could be demonstrated in excitable cells, using the GH3 pituitary cell line as a cell model. Our aims were: (1) to study the effect of K+ channel inhibition on the proliferation of GH3 cells; and (2) to investigate the putative intracellular signals involved in this inhibition. Tetraethylammonium chloride (TEA), a blocker of the calcium (Ca2+)-dependent K+ conductances of GH3, was found to reversibly inhibit cell proliferation, as measured by 3H-thymidine incorporation. Cell cycle block specifically occurred at the G1/S phase of the cell cycle. This inhibition of proliferation was observed for 1-4 mM TEA, which suppressed most of the Ca2+-activated K+ current and part of the inward rectifying K+ current, as shown by electrophysiological experiments. Increasing extracellular K+ concentrations with KCl also inhibited cell proliferation in a dose-dependent manner. Both TEA and KCl depolarized the cells and increased intracellular Ca2+ levels ([Ca2+]i), showing that, in this type of excitable cell, inhibition of cell proliferation can be associated with elevated Ca2+ levels. Ca2+ and membrane resting potential (MRP) were considered as possible messengers of this inhibition. Our results suggest that cell cycle arrest of GH3 cells by K+ channel block probably involves an additional pathway, distinct from those of Ca2+ and MRP. J. Cell. Physiol. 177:402-410, 1998. © 1998 Wiley-Liss, Inc.
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  • 44
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    Journal of Cellular Physiology 177 (1998), S. 387-395 
    ISSN: 0021-9541
    Keywords: Life and Medical Sciences ; Cell & Developmental Biology
    Source: Wiley InterScience Backfile Collection 1832-2000
    Topics: Biology , Medicine
    Notes: Previously, we reported that unaggressive, growth factor-dependent FET human colon carcinoma cells downregulated their transforming growth factor alpha (TGFα) expression in a quiescent state (G0/G1) induced by growth factor and nutrient deprivation (Mulder, 1991, Cancer Res., 51:2256-2262). In contrast, highly aggressive, growth factor-independent HCT116 human colon carcinoma cells aberrantly upregulated this autocrine activity in the quiescent state (Mulder, 1991, Cancer Res., 51:2256-2262; Howell et al., 1998, Mol. Cell. Biol., 18:303-313). In this report, the role of autocrine TGFα and the mechanism of its regulation of expression during reentry into the cell cycle from a noncycling growth state were determined in FET cells. Optimal induction of DNA synthesis from a quiescent state in FET cells is dependent upon autocrine TGFα as well as exogenous transferrin and insulin. Reentry into the cell cycle resulting from treatment with exogenous transferrin and insulin resulted in ∼3-fold induction of TGFα expression within 1 hr. TGFα induction was controlled at the transcription level, and the cis-controlling element was localized to the region between bp -370--201 relative to the translation start codon within the TGFα promoter. Thus neutralization of autocrine TGFα protein revealed that the induced TGFα autocrine activity was necessary for DNA synthesis and acted only in the early G1 phase of the cell cycle. Blockade of autocrine TGFα expression early in the cell cycle resulted in the reduction of DNA synthesis, whereas treatment with neutralization antibody at later times had no effect. This suggested that autocrine TGFα functions to initiate cell growth from noncycling states. This was further confirmed by the dependence of FET cells upon autocrine TGFα for colony formation in experiments where the plating density was sufficiently low to generate a lag phase in tissue culture. In contrast, TGFα autocrine activity was not required for exponential phase cells, as evidenced by the failure of TGFα neutralizing antibody to inhibit proliferation in this growth state. Taken together, these results suggest that autocrine TGFα acts primarily in the process of growth initiation by moving cells from a noncycling state back into the cell cycle, rather than supporting cell growth already initiated. J. Cell. Physiol. 177:387-395, 1998. © 1998 Wiley-Liss, Inc.
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  • 45
    ISSN: 0021-9541
    Keywords: Life and Medical Sciences ; Cell & Developmental Biology
    Source: Wiley InterScience Backfile Collection 1832-2000
    Topics: Biology , Medicine
    Notes: Basic fibroblast growth factor (bFGF, FGF-2) is progressively lost from mammary epithelial cells as they become malignant. To investigate the effects of restoring the expression of bFGF in breast cancer cells, we constructed MCF-7 cells that permanently overexpress 18-kD cytoplasm-localizing bFGF (MCF-7/ΔAFGF(18) cells) and cells that express both the 18-kD along with the 22- and 24-kD nucleus-localizing bFGF peptides (MCF-7/NCFFGF(18,22,24) cells), using retroviral transduction. These stable cell constructs grew more slowly and had a larger fraction of their populations in the G0/G1 phase of the cell cycle than control cells. All forms of bFGF were eluted from MCF-7/NCFFGF(18,22,24) cell monolayers with 2 M NaCl, in contrast to fibroblasts that were demonstrated to secrete only the 18-kD bFGF isoform. High-affinity binding of 18-kD 125I-bFGF to these cells was significantly decreased, probably because of competitive binding by the autocrine-secreted bFGF. Recombinant 18-kD bFGF that was previously demonstrated in our laboratory to inhibit proliferation, activate MAP kinase, and induce the cyclin-dependent kinase inhibitor p21WAF1/CIP1 in MCF-7 cells, further inhibited MCF-7/ΔAFGF(18) cells but had no effect on MCF-7/NCFFGF(18,22,24) cells. The total cellular content of the high-affinity FGF receptors 1-3 was unchanged, but FGF receptor 4 was decreased in MCF-7/NCFFGF(18,22,24) cells. Both cell types overexpressing bFGF isoforms had elevated levels of the cyclin-dependent kinase inhibitor p27Kip1 but not that of p21WAF1/CIP1. In MCF-7/ΔAFGF(18) cells, FGFR1 and MAP kinase were constitutively phosphorylated. Exogenous recombinant 18-kD bFGF did not accentuate these effects but did induce an increase in the levels of p21WAF1/CIP1 corresponding to the further inhibition induced by exogenous bFGF in these cells. In MCF-7/NCFFGF(18,22,24) cells, FGFR1 and MAP kinase were not phosphorylated at baseline nor upon stimulation with recombinant bFGF, and exogenous bFGF only had a minimal effect on low steady-state p21WAF1/CIP1 levels. However, stimulation of these cells with phorbol ester or insulin did result in MAP kinase phosphorylation. While growth-inhibited in the G1 phase of the cell cycle, MCF-7/NCFFGF(18,22,24) cells retained active isoforms of cdk2 and the hyperphosphorylated form of Rb. These data suggest that high molecular weight forms of bFGF overexpressed in MCF-7 cells do not activate the receptor-mediated MAP kinase pathway, and do not induce p21WAF1/CIP1 in an autocrine manner, but inhibit proliferation through other, possibly direct nuclear signalling mechanisms. J. Cell. Physiol. 177:411-425, 1998. © 1998 Wiley-Liss, Inc.
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  • 46
    ISSN: 0021-9541
    Keywords: Life and Medical Sciences ; Cell & Developmental Biology
    Source: Wiley InterScience Backfile Collection 1832-2000
    Topics: Biology , Medicine
    Notes: Bone marrow stromal cells (BMSCs) are a heterogeneous population of cells derived from colony-forming units-fibroblastic (CFU-Fs). These cells reside in the bone marrow cavity and are capable of differentiating into several cell phenotypes including osteoblasts, chondroblasts, hematopoiesis-supporting stromal cells, and adipocytes. However, the factors that regulate the proliferation and differentiation of the BMSC population are for the most part unknown. Since many members of the receptor tyrosine kinase (RTK) family have been shown to participate in growth control of various mesenchymal cell populations, in this study we examined the expression and function of RTKs in the BMSC population. Degenerate oligonucleotides corresponding to two conserved catalytic domains of the RTK family and RT-PCR were used initially to determine which RTKs are expressed in the human BMSC (hBMSC) system. After subcloning the amplification product generated from mRNA of a multicolony-derived hBMSC strain, PDGF receptor (β), EGF receptor, FGF receptor 1, and Axl were identified by DNA sequencing of 26 bacterial colonies. Furthermore, PDGF and EGF were found to enhance BMSC growth in a dose-dependent manner and to induce tyrosine phosphorylation of intracellular molecules, including the PDGF and EGF receptors themselves, demonstrating the functionality of these receptors. On the other hand, bFGF was found to have little effect on proliferation or tyrosine phosphorylation. Since single colony-derived hBMSC strains are known to vary from one colony to another in colony habit (growth rate and colony structure) and the ability to form bone in vivo, the expression levels of these RTKs were determined in 18 hBMSC clonal strains by semiquantitative RT-PCR and were found to vary from one clonal strain to another. While not absolutely predictive of the osteogenic capacity of individual clonal strains, on average, relatively high levels of PDGF-receptor were found in bone-forming strains, while on average, nonbone-forming strains had relatively high levels of EGF-receptor. Taken together, these results indicate that RTKs play a role in the control of hBMSC proliferation, and that the differential pattern of RTK expression may be useful in correlating the biochemical properties of individual clonal strains with their ability to produce bone in vivo. J. Cell. Physiol. 177:426-438, 1998. © 1998 Wiley-Liss, Inc.
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  • 47
    ISSN: 0021-9541
    Keywords: Life and Medical Sciences ; Cell & Developmental Biology
    Source: Wiley InterScience Backfile Collection 1832-2000
    Topics: Biology , Medicine
    Notes: Vascular endothelial growth factor-C (VEGF-C) is a recently characterized member of the VEGF family of angiogenic polypeptides. We demonstrate here that VEGF-C is angiogenic in vitro when added to bovine aortic or lymphatic endothelial (BAE and BLE) cells but has little or no effect on bovine microvascular endothelial (BME) cells. As reported previously for VEGF, VEGF-C and basic fibroblast growth factor (bFGF) induced a synergistic in vitro angiogenic response in all three cells lines. Unexpectedly, VEGF and VEGF-C also synergized in the in vitro angiogenic response when assessed on BAE cells. Characterization of VEGF receptor (VEGFR) expression revealed that BME, BAE, and BLE cell lines express VEGFR-1 and -2, whereas of the three cell lines assessed, only BAE cells express VEGFR-3. We also demonstrate that VEGF-C increases plasminogen activator (PA) activity in the three bovine endothelial cell lines and that this is accompanied by a concomitant increase in PA inhibitor-1. Addition of α2-antiplasmin to BME cells co-treated with bFGF and VEGF-C partially inhibited collagen gel invasion. These results demonstrate, first, that by acting in concert with bFGF or VEGF, VEGF-C has a potent synergistic effect on the induction of angiogenesis in vitro and, second, that like VEGF and bFGF, VEGF-C is capable of altering endothelial cell extracellular proteolytic activity. These observations also highlight the notion of context, i.e., that the activity of an angiogenesis-regulating cytokine depends on the presence and concentration of other cytokines in the pericellular environment of the responding endothelial cell. J. Cell. Physiol. 177:439-452, 1998. © 1998 Wiley-Liss, Inc.
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  • 48
    ISSN: 0021-9541
    Keywords: Life and Medical Sciences ; Cell & Developmental Biology
    Source: Wiley InterScience Backfile Collection 1832-2000
    Topics: Biology , Medicine
    Notes: Cell cycle control of histone H4 gene transcription is mediated by the multipartite promoter domain H4-Site II, which supports transcriptional activation at the G1/S phase transition and modulates basal H4 gene transcription. Proliferation-specific transcription is determined by the integrated activities of three distinct promoter factors interacting with H4-Site II: the interferon regulatory factor IRF-2 (synonymous with HiNF-M), HiNF-D (a complex between the homeodomain protein CDP-cut and the cell cycle mediators CDC2, cyclin A and pRB), as well as HiNF-P/H4TF-2. However, the contribution of HiNF-D to the enhancement and/or suppression of H4 gene transcription at specific cell cycle stages remains to be established. We used a panel of synchronized HeLa S3 cell lines containing stably integrated H4 promoter/CAT reporter gene constructs with mutations in H4-Site II. The temporal regulation of CAT mRNA accumulation under the control of the H4 promoter was analyzed by RNase protection analysis. Our main finding is that mutation of the HiNF-D/CDP-cut binding site alters the timing of histone gene activation during the cell cycle. Furthermore, our data indicate that HiNF-P/H4TF-2 may functionally compensate for HiNF-M/IRF-2 at Site II to regulate histone H4 gene transcription in HeLa S3 cervical carcinoma cells during early S phase. We postulate that HiNF-D (CDP-cut/cyclin A/CDC2/pRB containing complex) promotes HiNF-M/IRF-2 (and/or HiNF-P/H4TF-2) dependent histone H4 gene activation at the G1/S phase transition and attenuates H4 gene transcription at later cell cycle stages. The mechanistic division in the gene regulatory functions of the three H4-Site II binding proteins may ensure that histone H4 gene expression is stringently coupled with the onset of S phase in response to growth factor/cytokine-induced cell cycle progression. J. Cell. Physiol. 177:453-464, 1998. © 1998 Wiley-Liss, Inc.
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  • 49
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    Journal of Cellular Physiology 177 (1998), S. 465-473 
    ISSN: 0021-9541
    Keywords: Life and Medical Sciences ; Cell & Developmental Biology
    Source: Wiley InterScience Backfile Collection 1832-2000
    Topics: Biology , Medicine
    Notes: Human dermal fibroblasts suspended in a collagen matrix exhibit a 4-day delay in cell division, while the same cells in monolayer divided by day 1. The initial rates of 3H-thymidine incorporation by cells in monolayer or suspended in collagen were not significantly different. When suspended in collagen, there was a threefold increase in the proportion of cells in a tetraploidal (4N) DNA state compared to the same cells in monolayer. Flow cytometry analysis and 3H-thymidine incorporation studies identified the delay of cell division as a consequence of a block in the G2/M of the cell cycle and not an inhibition of DNA synthesis. The inclusion of 150 μ/ml of hyaluronic acid (HA) in the manufacture of fibroblast populated collagen lattices (FPCL) caused a stimulation of cell division, as determined by cell counting; increased the expression of tubulin, as determined by Western blot analysis; and reduced the proportion of cells in a 4N state, as determined by flow cytometry. HA added to the same cells growing in monolayer produced a minimal increase in the rate of cell division or DNA synthesis. HA supplementation of FPCLs stimulated cell division as well as tubulin concentrations, but it did not enhance lattice contraction. The introduction of tubulin isolated from pig brain or purchased tubulin into fibroblasts by electroporation prior to their transfer into collagen lattices promoted cell division in the first 24 hours and enhanced FPCL contraction. It is proposed that tubulin protein, the building blocks of microtubules, is limited in human fibroblasts residing within a collagen matrix. When human fibroblasts are suspended in collagen, one effect of added HA may be to stimulate the synthesis of tubulin which assists cells through the cell cycle. J. Cell. Physiol. 177:465-473, 1998. © 1998 Wiley-Liss, Inc.
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  • 50
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    Journal of Cellular Physiology 177 (1998), S. 474-482 
    ISSN: 0021-9541
    Keywords: Life and Medical Sciences ; Cell & Developmental Biology
    Source: Wiley InterScience Backfile Collection 1832-2000
    Topics: Biology , Medicine
    Notes: In this study we examined the regulation of cdk1 expression in normal human epidermal keratinocytes (HEKs) and neoplastic keratinocytes. Keratinocytes were growth-arrested by allowing the cells to grow to confluence or by treating them with interferon-gamma (IFNγ) or 12-O-tetradecanoyl phorbol-13-acetate (TPA). RT-PCR and Western blot analysis demonstrated that cdk1 was profoundly reduced in growth-arrested HEKs when compared with dividing HEKs. In contrast, a squamous carcinoma cell line, SCC25, did not growth-arrest in response to growth inhibitors and did not downregulate cdk1 expression. Transfection of HEKs with a reporter gene driven off a 2.5-kb fragment of the human cdk1 promoter indicated that the downregulation of cdk1 upon growth arrest was transcriptional. Deletion mapping of the cdk1 promoter indicated that a repressor region was located between -949--722 bp. This repressor region was not operative in the SCC25 cells. Examination of DNA:protein binding complexes by gel-shift analysis indicated that nuclear factors from both proliferative and growth-arrested cells bound to the DNA fragment spanning -949--722 bp. Further analysis revealed that this binding could be resolved into a constitutive and growth arrest-specific complex that bound in a similar fashion to regions spanning -892--831 bp and -831--774 bp, respectively. The putative growth arrest-specific complex was not found in contact-inhibited fibroblasts and was found at very low levels in SCC25 cells, indicating that the putative repressor binding was growth arrest-specific and possibly keratinocyte-specific. The binding complexes bound to these two fragments were localized, by competition analysis, to regions -874--853 bp and -830--800 bp. This is the first report of a transcriptional repressor being operative during keratinocyte growth arrest. J. Cell. Physiol. 177:474-482, 1998. © 1998 Wiley-Liss, Inc.
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  • 51
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    Journal of Cellular Physiology 177 (1998), S. 483-492 
    ISSN: 0021-9541
    Keywords: Life and Medical Sciences ; Cell & Developmental Biology
    Source: Wiley InterScience Backfile Collection 1832-2000
    Topics: Biology , Medicine
    Notes: Treatment with the sulfhydryl oxidant diamide denatures and aggregates cellular proteins, which prior studies have implicated as an oxidative damage that activates the heat shock transcription factor and induces thermotolerance. This study was initiated to further characterize cellular response to diamide-denatured proteins, including their involvement in diamide cytotoxicity. Cytotoxic diamide exposures at 37.0°C denatured and aggregated cellular proteins in a manner that was proportional to cell killing, but this correlation was different than that established for heated cells. Diamide exposures at 24.0°C were orders of magnitude less cytotoxic, with little additional killing occurring after diamide was removed and cells were returned to 37.0°C. Thus, protein denaturation that occurred at 37.0°C, after proteins were chemically destabilized by diamide at 24.0°C [Freeman et al., J. Cell. Physiol., 164:356-366 (1995) Senisterra et al., Biochemistry 36: 11002-11011 (1997)], had little effect on cell killing. Thermotolerance protected cells against diamide cytotoxicity but did not reduce the amount of denatured and aggregated protein observed immediately following diamide exposure. However, denatured/aggregated proteins in thermotolerant cells were disaggregated within 17 h following diamide exposure, while no disaggregation was observed in nontolerant cells. This more rapid disaggregation of proteins may be one mechanism by which thermotolerance protects cells against diamide toxicity, as it has been postulated to do against heat killing. As with heat shock, nontoxic diamide exposures induced maximal tolerance against heat killing; however, there was no detectable, increased synthesis of heat shock proteins. Thus, diamide treatment proved to be a reproducible procedure for inducing a phase of thermotolerance that does not require new heat shock protein (HSP) synthesis, without having to use transcription or translation inhibitors to suppress HSP gene expression.These results complement those from studies with other stresses to establish the importance of protein denaturation/aggregation as a cytotoxic consequence of stress and a trigger for thermotolerance induction. The data also illustrate that differences in how proteins are denatured and aggregated can affect their cytotoxicity and the manner in which thermotolerance is expressed. J. Cell. Physiol. 177:483-492, 1998. © 1998 Wiley-Liss, Inc.
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  • 52
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    Journal of Cellular Physiology 177 (1998), S. 499-499 
    ISSN: 0021-9541
    Keywords: Life and Medical Sciences ; Cell & Developmental Biology
    Source: Wiley InterScience Backfile Collection 1832-2000
    Topics: Biology , Medicine
    Notes: No abstract.
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  • 53
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    Journal of Cellular Physiology 177 (1998), S. 501-506 
    ISSN: 0021-9541
    Keywords: Life and Medical Sciences ; Cell & Developmental Biology
    Source: Wiley InterScience Backfile Collection 1832-2000
    Topics: Biology , Medicine
    Notes: CDK9 is a cdc2-related kinase protein. Previously named PITALRE, this protein is a serine-threonine kinase involved in many physiological processes. Unlike most of the cdc2-like kinases, its activity is not cell cycle-regulated. CDK9 acts preferentially in processes different from cell-cycle regulation, such as differentiation. Its cyclin partners, cyclins of T family, recently have been isolated. CDK9 immunoprecipitates with several unidentified polypeptides that may regulate its kinase activity. CDK9 has been shown to associate with the HIV-Tat protein, suggesting a possible involvement in AIDS. CDK9 recently was shown to be responsible for the kinase activity associated with the TAK complex and with the P-TEFb complex, suggesting activity also in the transcription process. J Cell Physiol 177:501-506, 1998. © 1998 Wiley-Liss, Inc.
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  • 54
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    Journal of Cellular Physiology 177 (1998), S. 493-498 
    ISSN: 0021-9541
    Keywords: Life and Medical Sciences ; Cell & Developmental Biology
    Source: Wiley InterScience Backfile Collection 1832-2000
    Topics: Biology , Medicine
    Notes: Ultraviolet light A (UVA) is shown to play an augmentative or synergistic role with UVB in pathophysiological conditions induced by solar radiation. Thus, UVA would contribute significantly to the development of skin malignancies. It remains unclear, however, how UVA contributes to solar radiation-induced immune suppression. Keratinocytes (KC) produce cytokines which are a significant mediator of inflammatory and immunologic reactions in skin exposed to solar radiation and are a potent mediator in the induction of immune suppression. To examine if UVA alters the expression and production of cytokines from KC, normal human keratinocytes (HuSK) were cultured and exposed to UVA at doses ranging between 2.5 and 20 kJ/m2. Constitutive expression of the p35 subunit of interleukin (IL)-12 was detected by reverse transcription-polymerase chain reaction (RT-PCR) and the p40 subunit was induced by UVA irradiation dose dependently. IL-12 protein was also detected in the supernatants from UVA-irradiated HuSK by enzyme-linked imuunosorbent assay (ELISA) and confirmed by a bioassay. On the other hand, the same doses of UVA did not induce IL-10 mRNA or IL-10 protein which has been shown to be one of the cytokines responsible for the induction of UVB-induced immunosuppression. Considering that IL-12 promotes activation of Th1 cells and prevents the activation of Th2 cells and that administration of IL-12 has been shown to block the induction of immune suppression in UV-irradiated animals, our results suggest that UVA modulates skin immune function distinctively from UVB by affecting the balance between IL-10 and IL-12 produced from KC. J. Cell. Physiol. 177:493-498, 1998. © 1998 Wiley-Liss, Inc.
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  • 55
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    Journal of Cellular Physiology 177 (1998), S. 507-517 
    ISSN: 0021-9541
    Keywords: Life and Medical Sciences ; Cell & Developmental Biology
    Source: Wiley InterScience Backfile Collection 1832-2000
    Topics: Biology , Medicine
    Notes: Neuropeptides, including mammalian bombesin-like peptides, act as potent cellular growth factors and have been implicated in a variety of normal and abnormal processes, including development, inflammation, and malignant transformation. These signaling peptides exert their characteristic effects on cellular processes by binding to specific G protein-coupled receptors (GPCR) on the surface of their target cells. Typically, the binding of a neuropeptide to its cognate GPCR triggers the activation of multiple signal transduction pathways that act in a synergistic and combinatorial fashion to relay the mitogenic signal to the nucleus and promote cell proliferation. A rapid increase in the synthesis of lipid-derived second messengers with subsequent activation of protein phosphorylation cascades is an important early response to neuropeptides. An emerging theme in signal transduction is that these agonists also induce rapid and coordinate tyrosine phosphorylation of cellular proteins including the nonreceptor tyrosine kinase p125fak and the adaptor proteins p130cas and paxillin. This tyrosine phosphorylation pathway depends on the integrity of the actin cytoskeleton and requires functional Rho. The purpose of this article is to review recent advances in unraveling the pathways that play a role in transducing mitogenic and migratory responses induced by G protein-coupled neuropeptide receptor agonists. J Cell Physiol 177:507-517, 1998. © 1998 Wiley-Liss, Inc.
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  • 56
    ISSN: 0021-9541
    Keywords: Life and Medical Sciences ; Cell & Developmental Biology
    Source: Wiley InterScience Backfile Collection 1832-2000
    Topics: Biology , Medicine
    Notes: The pentameric B subunit of verotoxin (VT) mediates the attachment to cell surface globotriaosyl ceramide (Gb3) to facilitate receptor-mediated endocytosis of the toxin. In highly toxin-sensitive tumor cells, the holotoxin and VT1 B subunit is targeted intracellularly to elements of the endoplasmic reticulum (ER)/nuclear membrane. In less sensitive cells, the toxin is targeted to components of the Golgi apparatus. We have studied two cell systems: the induced VT hypersensitivity of human astrocytoma cell lines cultured in the presence of sodium butyrate (compared to sodium propionate and capronate) and the increased VT sensitivity of multiple drug-resistant mutants as compared to parental human ovarian carcinoma cells. In both cases, a difference in the intracellular retrograde transport of the receptor-bound internalized toxin to the ER/nuclear envelope, as opposed to the Golgi, correlated with a 〉1,000-fold increase in cell sensitivity to VT. This change in intracellular routing may be due to sorting of Gb3 fatty acid isoforms, since nuclear targeting was found in turn to correlate with the preferential synthesis of Gb3 containing shorter chain (primarily C16) fatty acid species. We propose that the isoform-dependent traffic of Gb3 from the cell surface to the ER/nuclear membrane provides a new signal transduction pathway for Gb3 binding proteins. J Cell Physiol 177:646-660, 1998. © 1998 Wiley-Liss, Inc.
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  • 57
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    Journal of Cellular Biochemistry 71 (1998), S. 313-327 
    ISSN: 0730-2312
    Keywords: articular cartilage repair ; tissue engineering ; collagen type II ; collagen type IX ; collagen network ; pyridinium crosslinks ; Life and Medical Sciences ; Cell & Developmental Biology
    Source: Wiley InterScience Backfile Collection 1832-2000
    Topics: Biology , Chemistry and Pharmacology , Medicine
    Notes: The function of articular cartilage as a weight-bearing tissue depends on the specific arrangement of collagen types II and IX into a three-dimensional organized collagen network that can balance the swelling pressure of the proteoglycan/ water gel. To determine whether cartilage engineered in vitro contains a functional collagen network, chondrocyte-polymer constructs were cultured for up to 6 weeks and analyzed with respect to the composition and ultrastructure of collagen by using biochemical and immunochemical methods and scanning electron microscopy. Total collagen content and the concentration of pyridinium crosslinks were significantly (57% and 70%, respectively) lower in tissue-engineered cartilage that in bovine calf articular cartilage. However, the fractions of collagen types II, IX, and X and the collagen network organization, density, and fibril diameter in engineered cartilage were not significantly different from those in natural articular cartilage. The implications of these findings for the field of tissue engineering are that differentiated chondrocytes are capable of forming a complex structure of collagen matrix in vitro, producing a tissue similar to natural articular cartilage on an ultrastructural scale. J. Cell. Biochem. 71:313-327, 1998. © 1998 Wiley-Liss, Inc.
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    Journal of Cellular Biochemistry 71 (1998), S. 328-339 
    ISSN: 0730-2312
    Keywords: insulin ; heart ; development ; PI 3-kinase ; protein kinase B ; S6 kinase ; casein kinase 2 ; Life and Medical Sciences ; Cell & Developmental Biology
    Source: Wiley InterScience Backfile Collection 1832-2000
    Topics: Biology , Chemistry and Pharmacology , Medicine
    Notes: The control of glucose uptake and glycogen metabolism by insulin in target organs is in part mediated through the regulation of protein-serine/ threonine kinases. In this study, the expression and phosphotransferase activity levels of some of these kinases in rat heart ventricle were measured to investigate whether they might mediate the shift in the energy dependency of the developing heart from glycogen to fatty acids. Following tail-vein injection of overnight fasted adult rats with 2 U of insulin per kg body weight, protein kinase B (PKB), the 70-kDa ribosomal S6 kinase (S6K), and casein kinase 2 (CK2) were activated (30-600%), whereas the MAP/ extracellular regulated kinases (ERK)1 and ERK2 were not stimulated under these conditions. When the expression levels of the insulin-activated kinases were probed with specific antibodies in ventricular extracts from 1-, 10-, 20-, 50-, and 365-day-old rats, phosphatidylinositol 3-kinase (PI3K), PKB, S6K, and CK2 were downregulated (40-60%) with age. By contrast, ventricular glycogen synthase kinase-3β (GSK3β) protein levels were maintained during postnatal development. Similar findings were obtained when the expression of these kinases was investigated in freshly isolated ventricular myocytes, where they were detected predominantly in the cytosolic fraction of the myocytes. Compared to other adult rat tissues such as brain and liver, the levels of PI3K, PKB, S6K, and GSK3β were relatively low in the heart. Even though CK2 protein and activity levels were reduced by ∼60% in 365 day as compared to 1-day-old rats, expression of CK2 in the adult heart was as high as detected in any of the other rat tissues. The high basal activities of CK2 in early neonatal heart may be associated with the proliferating state of myocytes. J. Cell. Biochem. 71:328-339, 1998. © 1998 Wiley-Liss, Inc.
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  • 59
    ISSN: 0730-2312
    Keywords: vitamin D analogues ; vitamin D receptor ; ligand binding ; limited protease digestion ; ligand-dependent gel shift assay ; gene regulation ; Life and Medical Sciences ; Cell & Developmental Biology
    Source: Wiley InterScience Backfile Collection 1832-2000
    Topics: Biology , Chemistry and Pharmacology , Medicine
    Notes: The nuclear hormone 1α,25-dihydroxyvitamin D3 (VD) has important cell-regulatory functions but also a strong calcemic effect. Therefore, various VD analogues have been synthesized and screened for their biological profile. In order to gain more insight into the molecular basis of the high antiproliferative but low calcemic action of the VD analogue EB1089, we characterized this compound in comparison to five structurally related VD analogues. The activities of the six VD analogues in in vitro assays (limited protease digestion assays for determining interaction with monomeric vitamin D receptor (VDR), ligand-dependent gel shift assays for showing the increase of DNA binding of VDR-retinoid X receptor (RXR) heterodimers, and reporter gene assays on different types of VD response elements for demonstrating the efficacy in nuclear VD signalling) were found to represent their biological potency (antiproliferative effect on different malignant cell lines). In this series, EB1089 proved to be the most potent VD analogue; that is, every structural modification (20-epi configuration, cis-configuration at position C24, or changes at the ethyl groups at position C25) appeared to reduce the determined activities mediated through the VDR of these analogues. Moreover, the modifications of EB1089 resulted in a loss of VD response element selectivity, suggesting that this parameter is very critical for the biological profile of this VD analogue. J. Cell. Biochem. 71:340-350, 1998. © 1998 Wiley-Liss, Inc.
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  • 60
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    Journal of Cellular Biochemistry 71 (1998), S. 363-374 
    ISSN: 0730-2312
    Keywords: nuclear matrix proteins ; preparation method ; two-dimensional polyacrylamide gel electrophoresis ; heterogeneous nuclear ribonucleoproteins ; vanadyl ribonucleoside complexes ; Life and Medical Sciences ; Cell & Developmental Biology
    Source: Wiley InterScience Backfile Collection 1832-2000
    Topics: Biology , Chemistry and Pharmacology , Medicine
    Notes: Comparative analysis of nuclear matrix proteins by two-dimensional electrophoresis may be greatly impaired by copurifying cytoskeletal proteins. The present data show that the bulk of adhering cytofilaments may mechanically be removed by shearing of nuclei pretreated with vanadyl ribonucleoside complexes. Potential mechanisms of action not based on ribonuclease inhibition are discussed. To individually preserve the integrity of nuclear structures, we developed protocols for the preparation of nuclear matrices from three categories of cells, namely leukocytes, cultured cells, and tissue cells. As exemplified with material from human lymphocytes, cultured amniotic cells, and liver tissue cells, the resulting patterns of nuclear matrix proteins appeared quite similar. Approximately 300 spots were shared among the cell types. Forty-nine of these were identified, 21 comprising heterogeneous nuclear ribonucleoproteins. Heterogeneous nuclear ribonucleoproteins L and nuclear lamin B2 isoforms were identified by amino acid sequencing and mass spectrometry. However, individually expressed proteins, such as the proliferating cell nuclear antigen, also pertained following application of the protocols. Thus, enhanced resolution and comparability of proteins improve systematic analyses of nuclear matrix proteins from various cellular sources. J. Cell. Biochem. 71:363-374, 1998. © 1998 Wiley-Liss, Inc.
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  • 61
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    Journal of Cellular Biochemistry 71 (1998), S. 375-381 
    ISSN: 0730-2312
    Keywords: insulin-like growth factor-I ; insulin-like growth factor binding protein-5 ; smooth muscle cells ; atherosclerosis ; substratum ; Life and Medical Sciences ; Cell & Developmental Biology
    Source: Wiley InterScience Backfile Collection 1832-2000
    Topics: Biology , Chemistry and Pharmacology , Medicine
    Notes: Insulin-like growth factor binding protein-5 (IGFBP-5) is synthesized and secreted by smooth muscle cells (SMC). IGFBP-5 synthesis is stimulated five- to sixfold by IGF-I, and IGFBP-5 has been shown to augment IGF-I-stimulated DNA synthesis in this cell type. The ability of IGFBP-5 to augment the SMC response to IGF-I is dependent upon its binding to extracellular matrix. A highly charged region of IGFBP-5 that contains amino acids in positions 201-218 has been shown to mediate binding of IGFBP-5 to human fibroblast extracellular matrix (ECM), and a synthetic peptide containing this sequence inhibits IGFBP-5 binding to fibroblast ECM. In this study we show that exposure of SMC cultures that are constituitively synthesizing IGFBP-5 to a synthetic peptide (termed peptide A) containing this sequence has no effect on its synthesis but reduces its abundance within the ECM. The addition of increasing concentrations of the peptide to SMC cultures resulted in a concentration-dependent reduction in ECM-associated IGFBP-5. In contrast, a control peptide (peptide B), which contained the region of amino acids in positions 131-141 and had a similar charge-to-mass ratio, caused a minimal decrease in ECM binding. This effect was functionally significant since the addition of 10 μg/ ml of peptide A inhibited the cellular replication response to 10 ng/ ml IGF-I by 51%, and peptide B had no effect. The effects of peptide A were not due to nonspecific cytotoxicity since it had no inhibitory effect on the response of these cells to human serum and was associated with only minimal inhibition of the cellular response to platelet-derived growth factor. The findings suggest that inhibiting IGFBP-5 binding to porcine SMC ECM results in reduced cellular responses to IGF-I. J. Cell. Biochem. 71:375-381, 1998. © 1998 Wiley-Liss, Inc.
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  • 62
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    Journal of Cellular Biochemistry 71 (1998), S. 382-391 
    ISSN: 0730-2312
    Keywords: dexamethasone ; bone marrow cell cultures ; IGF-I ; vertebrae ; Life and Medical Sciences ; Cell & Developmental Biology
    Source: Wiley InterScience Backfile Collection 1832-2000
    Topics: Biology , Chemistry and Pharmacology , Medicine
    Notes: Osteoblast-like cell cultures have been established from the marrow of adult rat vertebrae. We have simultaneously examined the response to dexamethasone (dex) treatment in cultures of young adult female vertebral and femoral marrow cells. Alkaline phosphatase (AP) activity was analyzed as well as the expression of mRNAs for osteocalcin (OC) and insulin-like growth factor I (IGF-I). The vertebral and femoral marrow cells were maintained for 7 days in primary culture with or without 10-8 M dex and then 6 days in secondary culture without dex or with 10-8 M or 10-7 M dex. All cells were examined on day 6 of secondary culture. Vertebral and femoral cultures each expressed the highest AP enzyme levels when grown with dex in primary culture (10-8 M) and secondary culture (10-7 M). Under all experimental conditions, vertebral cultures had lower AP enzyme activity than femoral cultures. When dex was omitted from secondary culture, OC gene expression was not detected in either vertebral or femoral passaged cells even if dex was present in primary culture. For dex conditions where OC was expressed, vertebral cultures had higher OC mRNA steady-state levels than femoral cultures. IGF-I gene expression was detected by Northern analysis in both vertebral and femoral secondary cultures. However, vertebral marrow cultures had much higher IGF-I mRNA levels compared to femoral cultures whether or not dex was present in primary culture. These findings demonstrate that dex supports the differentiation of both vertebral and femoral adult marrow osteogenic cells into osteoblasts. Our results support the hypothesis that osteoblastic marrow cultures differ depending upon which location in the skeleton they are from and that there are skeletal site-dependent differences in the insulin-like growth factor system components. J. Cell. Biochem. 71:382-391, 1998. © 1998 Wiley-Liss, Inc.
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  • 63
    ISSN: 0730-2312
    Keywords: apoptosis ; necrosis ; phospholipases ; tumor necrosis factor ; Fas ; Life and Medical Sciences ; Cell & Developmental Biology
    Source: Wiley InterScience Backfile Collection 1832-2000
    Topics: Biology , Chemistry and Pharmacology , Medicine
    Notes: Phospholipases generate important secondary messengers in several cellular processes, including cell death. Tumor necrosis factor (TNF) can induce two distinct modes of cell death, viz. necrosis and apoptosis. Here we demonstrate that phospholipase D (PLD) and cytosolic phospholipase A2 (cPLA2) are differentially activated during TNF-induced necrosis or apoptosis. Moreover, a comparative study using TNF and anti-Fas antibodies as cell death stimuli showed that PLD and cPLA2 are specifically activated by TNF. These results indicate that both the mode of cell death and the type of death stimulus determine the potential role of phospholipases as generators of secondary messengers. J. Cell. Biochem. 71:392-399, 1998. © 1998 Wiley-Liss, Inc.
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  • 64
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    Keywords: IGFBP ; cAMP ; PKA ; prostaglandin ; bone ; Life and Medical Sciences ; Cell & Developmental Biology
    Source: Wiley InterScience Backfile Collection 1832-2000
    Topics: Biology , Chemistry and Pharmacology , Medicine
    Notes: Insulin-like growth factor (IGF)-I and IGF-II are expressed at biologically effective levels by bone cells. Their stability and activity are modulated by coexpression of IGF binding proteins (IGFBPs). Secreted IGFBPs may partition to soluble, cell-associated, and matrix-bound compartments. Extracellular localization may sequester, store, or present IGFs to appropriate receptors. Of the six IGFBPs known, rat osteoblasts synthesize all but IGFBP-1. Of these, IGFBP-3, -4, and -5 mRNAs are induced by an increase in cAMP. Little is known about extracellular IGFBP localization in bone and nothing about IGFBP expression by nonosteoblastic periosteal bone cells. We compared basal IGFBP expression in periosteal and osteoblast bone cell cultures and assessed the effects of changes in cAMP-dependent protein kinase A or protein kinase C. Basal IGFBP gene expression differed principally in that more IGFBP-2 and -5 occurred in osteoblast cultures, and more IGFBP-3 and -6 occurred in periosteal cultures. An increase in cAMP enhanced IGFBP-3, -4, and -5 mRNA and accordingly increased soluble IGFBP-3, -4, and -5 and matrix-bound IGFBP-3 and -5 in both bone cell populations. In contrast, protein kinase C activators suppressed IGFBP-5 mRNA, and its basal protein levels remained very low. We also detected low Mr bands reactive with antisera to IGFBP-2, -3, and -5, suggesting proteolytic processing or degradation. Our studies reveal that various bone cell populations secrete and bind IGFBPs in selective ways. Importantly, inhibitory IGFBP-4 does not significantly accumulate in cell-associated compartments, even though its secretion is enhanced by cAMP. Because IGFBPs bind IGFs less tightly in cell-bound compartments, they may prolong anabolic effects by agents that increase bone cell cAMP. J. Cell. Biochem. 71:351-362, 1998. © 1998 Wiley-Liss, Inc.
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    Journal of Cellular Biochemistry 72 (1998), S. 8-17 
    ISSN: 0730-2312
    Keywords: eukaryote ; DNA replication ; replication origin ; pre-replication complex ; initiation proteins ; origin recognition complex ; DNA unwinding ; nuclear structure ; chromatin structure ; DNA methylation ; animal development ; metazoa ; mammal ; frog ; fly ; yeast ; Xenopus ; Drosophila ; Sciara ; Life and Medical Sciences ; Cell & Developmental Biology
    Source: Wiley InterScience Backfile Collection 1832-2000
    Topics: Biology , Chemistry and Pharmacology , Medicine
    Notes: Our understanding of the process by which eukaryotes regulate initiation of DNA replication has made remarkable advances in the past few years, thanks in large part to the explosion of genetic and biochemical information on the budding yeast, Saccharomyces cerevisiae. At least three major concepts have emerged: 1) The sequence of molecular events that determines when replication begins and how frequently each replication site is used are conserved among most, if not all, eukaryotes; 2) specific replication origins are used in most, if not all, eukaryotes that consist of a flexible modular anatomy; and 3) epigenetic factors such as chromatin structure and nuclear organization determine which of many potential replication origins are used at different stages in animal development. Thus, the current state of our knowledge suggests a simple unifying concept - all eukaryotes utilize the same basic proteins and DNA sequences to initiate replication, but the metazoa can change both the number and locations of replication origins in response to the demands of animal development. J. Cell. Biochem. Suppls. 30/31:8-17, 1998.
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  • 66
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    Journal of Cellular Biochemistry 72 (1998), S. 168-176 
    ISSN: 0730-2312
    Keywords: cadherin ; catenin ; differentiation ; Life and Medical Sciences ; Cell & Developmental Biology
    Source: Wiley InterScience Backfile Collection 1832-2000
    Topics: Biology , Chemistry and Pharmacology , Medicine
    Notes: Cadherins form a family of cell-cell adhesion proteins that are critical to normal embryonic development. Expression of the various family members is regulated in a complex pattern during embryogenesis. Both reduced and inappropriate expression of cadherins have been associated with abnormal tissue formation in embryos and tumorigenesis in mature organisms. Evidence is accumulating that signals unique to individual members of the cadherin family, as well as signals common to multiple cadherins, contribute to the differentiated phenotype of various cell types. While a complete understanding of the regulation of cadherin expression of the molecular nature of intracellular signaling downstream of cadherin adhesion is essential to an understanding of embryogenesis and tumorigenesis, our knowledge in both areas is inadequate. Clearly, elucidating the factors and conditions that regulate cadherin expression and defining the signaling pathways activated by cadherins are frontiers for future research. J. Cell. Biochem. Suppls. 30/31:168-176, 1998. © 1998 Wiley-Liss, Inc.
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    Journal of Cellular Biochemistry 72 (1998), S. 129-136 
    ISSN: 0730-2312
    Keywords: protein kinase CK2 ; holoenzyme ; α- and β-subunits ; Life and Medical Sciences ; Cell & Developmental Biology
    Source: Wiley InterScience Backfile Collection 1832-2000
    Topics: Biology , Chemistry and Pharmacology , Medicine
    Notes: Protein kinase CK2 is a ubiquitous eukaryotic ser/thr protein kinase. The active holoenzyme is a heterotetrameric protein composed of catalytic (α and α′) and regulatory (β) subunits that phosphorylates many different protein substrates and appears to be involved in the regulation of cell division. Despite important structural studies, the intimate details of the interactions of the α catalytic subunits with the β regulatory subunits are unknown. Recent evidence that indicates that both CK2 subunits can interact promiscuously with other proteins in a manner that excludes the binding of their complementary CK2 partners has opened the possibility that the phosphorylating activity of this enzyme may be regulated in a novel way. These alternative interactions could limit the in vivo availability of CK2 subunits to generate fully active holoenzyme CK2 tetramers. Likewise, variations in the ratio of α- and β-subunits could determine the activity of several phosphorylating and dephosphorylating activities. The promiscuity of the CK2 subunits can be extrapolated to a more widespread phenomenon in which “wild-card” proteins could act as general switches by interacting and regulating several catalytic activities. J. Cell. Biochem. Suppls. 30/31:129-136, 1998. © 1998 Wiley-Liss, Inc.
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  • 68
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    Journal of Cellular Biochemistry 72 (1998), S. 177-184 
    ISSN: 0730-2312
    Keywords: nucleosome ; chromosomes ; DNA ; Life and Medical Sciences ; Cell & Developmental Biology
    Source: Wiley InterScience Backfile Collection 1832-2000
    Topics: Biology , Chemistry and Pharmacology , Medicine
    Notes: No abstract.
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  • 69
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    Journal of Cellular Biochemistry 72 (1998), S. 194-202 
    ISSN: 0730-2312
    Keywords: acute leukemias ; hematopoietic cells ; histone deacetylase complexes ; Life and Medical Sciences ; Cell & Developmental Biology
    Source: Wiley InterScience Backfile Collection 1832-2000
    Topics: Biology , Chemistry and Pharmacology , Medicine
    Notes: Accumulating evidence points to a connection between cancer and transcriptional control by histone acetylation and deacetylation. This is particularly true with regard to the acute leukemias, many of which are caused by fusion proteins that have been created by chromosomal translocations. Genetic rearrangements that disrupt the retinoic acid receptor-α and acute myeloid leukemia-1 genes create fusion proteins that block terminal differentiation of hematopoietic cells by repressing transcription. These fusion proteins interact with nuclear hormone co-repressors, which recruit histone deacetylases to promoters to repress transcription. This finding suggests that proteins within the histone deacetylase complexes may be potential targets for pharmaceutical intervention in many leukemia patients. J. Cell. Biochem. Suppls. 30/31:194-202, 1998. © 1998 Wiley-Liss, Inc.
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  • 70
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    Journal of Cellular Biochemistry 72 (1998), S. 185-193 
    ISSN: 0730-2312
    Keywords: steroid receptor action ; co-repressors ; co-activators ; Life and Medical Sciences ; Cell & Developmental Biology
    Source: Wiley InterScience Backfile Collection 1832-2000
    Topics: Biology , Chemistry and Pharmacology , Medicine
    Notes: During the past few years, our understanding of nuclear receptor action has dramatically improved as a result of the identification and functional analysis of co-regulators such as factors involved in chromatin remodeling, transcription intermediary factors (co-repressors and co-activators), and direct interactions with the basal transcriptional machinery. Furthermore, the elucidation of the crystal structures of the empty ligand-binding domains of the nuclear receptor and of complexes formed by the nuclear receptor's ligand-binding domain bound to agonists and antagonists has contributed significantly to our understanding of the early events of nuclear receptor action. However, the picture of hormone- and hormone receptor-mediated mechanisms of gene regulation remain incomplete and extremely complicated when one also considers the “nontraditional” interactions of hormone-activated nuclear receptors, for example, interactions between the activated steroid receptors and components of the chromatin/nuclear matrix; and finally the nongenomic effects that steroid hormones can exhibit with other signaling pathways. In this prospectus on steroid receptors, we discuss the implications of various steroid hormone and nuclear receptor interactions and potential future directions of investigation. J. Cell. Biochem. Suppls. 30/31:185-193, 1998. © 1999 Wiley-Liss, Inc.
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  • 71
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    Journal of Cellular Biochemistry 72 (1998), S. 214-219 
    ISSN: 0730-2312
    Keywords: nucleus ; nuclear envelope ; nuclear export ; nuclear import ; regulation ; Life and Medical Sciences ; Cell & Developmental Biology
    Source: Wiley InterScience Backfile Collection 1832-2000
    Topics: Biology , Chemistry and Pharmacology , Medicine
    Notes: The control of transcription and translation is of fundamental importance in cell biology. In this regard, the nuclear envelope is in a unique position to contribute to the regulation of these events, by directing macromolecular exchanges between the nucleus and cytoplasm. Such exchanges occur through the nuclear pore complexes, mainly by signal-mediated processes. Different signals are required for import and export. Specific cytoplasmic or nuclear receptors initially bind the signal-containing substrate, and the complex subsequently interacts with the pores. Additional factors then assist in translocation across the envelope. Current research is focused mainly on further characterization of transport receptors, translocation factors, as well as components of the nuclear pore complex, i.e., the nucleoporins. The ultimate goal is to understand the molecular interactions that occur among the different components of the transport apparatus, the energy sources for transport, and how variations in transport capacity are generated. J. Cell. Biochem. Suppls. 30/31:214-219, 1998. © 1998 Wiley-Liss, Inc.
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  • 72
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    Journal of Cellular Biochemistry 72 (1998), S. 220-231 
    ISSN: 0730-2312
    Keywords: nuclear architecture ; gene expression ; tumor cells ; Life and Medical Sciences ; Cell & Developmental Biology
    Source: Wiley InterScience Backfile Collection 1832-2000
    Topics: Biology , Chemistry and Pharmacology , Medicine
    Notes: Functional interrelationships between components of nuclear architecture and control of gene expression are becoming increasingly evident. There is growing appreciation that multiple levels of nuclear organization integrate the regulatory cues that support activation and suppression of genes as well as the processing of gene transcripts. The linear organization of genes and promoter elements provide the potential for responsiveness to physiological regulatory signals. Parameters of chromatin structure and nucleosome organization support synergism between activities at independent regulatory sequences and render promoter elements accessible or refractory to transcription factors. Association of genes, transcription factors, and the machinery for transcript processing with the nuclear matrix facilitates fidelity of gene expression within the three-dimensional context of nuclear architecture. Mechanisms must be defined that couple nuclear morphology with enzymatic parameters of gene expression. The recent characterization of factors that mediate chromatin remodeling and intranuclear targeting signals that direct transcription factors to subnuclear domains where gene expression occurs, reflect linkage of genetic and structural components of transcriptional control. Nuclear reorganization and aberrant intranuclear trafficking of transcription factors for developmental and tissue-specific control that occurs in tumor cells and in neurological disorders provides a basis for high resolution diagnostics and targeted therapy. J. Cell. Biochem. Suppls. 30/31:220-231, 1998. © 1998 Wiley-Liss, Inc.
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  • 73
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    Journal of Cellular Biochemistry 72 (1998), S. 232-237 
    ISSN: 0730-2312
    Keywords: cytoskeleton, mechanotransduction, integrins, cell architecture, tensegrity ; Life and Medical Sciences ; Cell & Developmental Biology
    Source: Wiley InterScience Backfile Collection 1832-2000
    Topics: Biology , Chemistry and Pharmacology , Medicine
    Notes: The field of molecular cell biology has experienced enormous advances over the last century by reducing the complexity of living cells into simpler molecular components and binding interactions that are amenable to rigorous biochemical analysis. However, as our tools become more powerful, there is a tendency to define mechanisms by what we can measure. The field is currently dominated by efforts to identify the key molecules and sequences that mediate the function of critical receptors, signal transducers, and molecular switches. Unfortunately, these conventional experimental approaches ignore the importance of supramolecular control mechanisms that play a critical role in cellular regulation. Thus, the significance of individual molecular constituents cannot be fully understood when studied in isolation because their function may vary depending on their context within the structural complexity of the living cell. These higher-order regulatory mechanisms are based on the cell's use of a form of solid-state biochemistry in which molecular components that mediate biochemical processing and signal transduction are immobilized on insoluble cytoskeletal scaffolds in the cytoplasm and nucleus. Key to the understanding of this form of cellular regulation is the realization that chemistry is structure and hence, recognition of the importance of architecture and mechanics for signal integration and biochemical control. Recent work that has unified chemical and mechanical signaling pathways provides a glimpse of how this form of higher-order cellular control may function and where paths may lie in the future. J. Cell. Biochem. Suppls. 30/31:232-237, 1998. © 1998 Wiley-Liss, Inc.
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  • 74
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    Journal of Cellular Biochemistry 72 (1998), S. 250-263 
    ISSN: 0730-2312
    Keywords: signal transduction ; cell adhesion complexes ; membrane skeleton ; nucleo-cytoplasmic translocation ; Life and Medical Sciences ; Cell & Developmental Biology
    Source: Wiley InterScience Backfile Collection 1832-2000
    Topics: Biology , Chemistry and Pharmacology , Medicine
    Notes: Understanding how the information is conveyed from outside to inside the cell is a critical challenge for all biologists involved in signal transduction. The flow of information initiated by cell-cell and cell-extracellular matrix contacts is mediated by the formation of adhesion complexes involving multiple proteins. Inside adhesion complexes, connective membrane skeleton (CMS) proteins are signal transducers that bind to adhesion molecules, organize the cytoskeleton, and initiate biochemical cascades. Adhesion complex-mediated signal transduction ultimately directs the formation of supramolecular structures in the cell nucleus, as illustrated by the establishment of multi complexes of DNA-bound transcription factors, and the redistribution of nuclear structural proteins to form nuclear subdomains. Recently, several CMS proteins have been observed to travel to the cell nucleus, suggesting a distinctive role for these proteins in signal transduction. This review focuses on the nuclear translocation of structural signal transducers of the membrane skeleton and also extends our analysis to possible translocation of resident nuclear proteins to the membrane skeleton. This leads us to envision the communication between spatially distant cellular compartments (i.e., membrane skeleton and cell nucleus) as a bidirectional flow of information (a dynamic reciprocity) based on subtle multilevel structural and biochemical equilibria. At one level, it is mediated by the interaction between structural signal transducers and their binding partners, at another level it may be mediated by the balance and integration of signal transducers in different cellular compartments. J. Cell. Biochem. Suppls. 30/31:250-263, 1998. © 1998 Wiley-Liss, Inc.
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  • 75
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    Journal of Cellular Biochemistry 72 (1998), S. 284-285 
    ISSN: 0730-2312
    Keywords: Life and Medical Sciences ; Cell & Developmental Biology
    Source: Wiley InterScience Backfile Collection 1832-2000
    Topics: Biology , Chemistry and Pharmacology , Medicine
    Notes: No abstract.
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  • 76
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    Journal of Cellular Biochemistry 72 (1998), S. 297-303 
    ISSN: 0730-2312
    Keywords: tissue engineering ; biomaterials ; cell culture ; polymers ; transplants ; Life and Medical Sciences ; Cell & Developmental Biology
    Source: Wiley InterScience Backfile Collection 1832-2000
    Topics: Biology , Chemistry and Pharmacology , Medicine
    Notes: This article reviews the important developments in the field of tissue engineering over the last 10 years. Research in the area of biomaterials is examined from the perspective of providing the foundation for the development of tissue engineering. Early efforts combining cells with biocompatible materials are described and applications of this technology presented, with particular focus on uses in orthopaedics and maxillofacial surgery. The basic principles of tissue engineering and state-of-the-art technology in cell biology and materials science as used currently in the field are presented. Finally, futures challenges are outlined from the perspective of integrating technologies from medicine, biology, and engineering, in hopes of translating tissue engineering to clinical applications. J. Cell. Biochem. Suppls. 30/31:297-303, 1998. © 1998 Wiley-Liss, Inc.
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  • 77
    ISSN: 0730-2312
    Keywords: EST ; cDNA microarray ; RDA ; osteoblast differentiation ; pax-6 ; Life and Medical Sciences ; Cell & Developmental Biology
    Source: Wiley InterScience Backfile Collection 1832-2000
    Topics: Biology , Chemistry and Pharmacology , Medicine
    Notes: Elucidation of the changes in gene expression associated with biological processes is a central problem in biology. Advances in molecular and computational biology have led to the development of powerful, high-thoughput methods for the analysis of differential gene expression. These tools have opened up new opportunities in disciplines ranging from cell and developmental biology to drug development and pharmacogenomics. In this review, the attributes of five commonly used differential gene expression methods are discussed: expressed sequence tag (EST) sequencing, cDNA microarray hybridization, subtractive cloning, differential display, and serial analysis of gene expression (SAGE). The application of EST sequencing and microarray hybridization is illustrated by the discovery of novel genes associated with osteoblast differentiation. The application of subtractive cloning is presented as a tool to identify genes regulated in vivo by the transcription factor pax-6. These and other examples illustrate the power of genomics for discovering novel genes that are important in biology and which also represent new targets for drug development. The central theme of the review is that each of the approaches to identifying differentially expressed genes is useful, and that the experimental context and subsequent evaluation of differentially expressed genes are the critical features that determine success. J. Cell. Biochem. Suppls. 30/31:286-296, 1998. © 1998 Wiley-Liss, Inc.
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    Journal of Cellular Biochemistry 72 (1998), S. 264-276 
    ISSN: 0730-2312
    Keywords: Life and Medical Sciences ; Cell & Developmental Biology
    Source: Wiley InterScience Backfile Collection 1832-2000
    Topics: Biology , Chemistry and Pharmacology , Medicine
    Notes: Genes involved in chromosomal translocations, associated with the formation of fusion proteins in leukemia, are modular in nature and regulatory in function. It is likely that they are involved in the initiation and maintenance of normal hematopoiesis. A conceptual model is proposed by which disruption of these different genes leads to the development of acute leukemia. Central to this model is the functional interaction between the mammalian trithorax and polycomb group protein complexes. Many of the genes identified in leukemia-associated translocations are likely upstream regulators, co-participators or downstream targets of these complexes. In the natural state, these proteins interact with each other to form multimeric higher-order structures, which sequentially regulate the development of the normal hematopoietic state, either through HOX gene expression or other less defined pathways. The novel interaction domains acquired by the chimaeric fusion products subvert normal cellular control mechanisms, which result in both a failure of cell maturation and activation of anti-apoptotic pathways. The mechanisms by which these translocation products are able to affect these processes are thought to lie at the level of chromatin-mediated transcriptional activation and/or repression. The stimuli for proliferation and development of clinically overt disease may require subsequent mutations in more than one oncogene or tumor suppressor gene, or both. A more comprehensive catalogue of mutation events in malignant cells is therefore required to understand the key regulatory networks that serve to maintain multipotentiality and in particular the modifications which initiate and coordinate commitment in differentiating hematopoietic cells. We propose a model in which common pathways for leukemogenesis lie along the cell cycle control of chromatin structure in terms of transcriptional activation or repression. A clearer understanding of this cascade will provide opportunities for the design and construction of novel biological agents that are able to restore normal regulatory mechanisms. J. Cell. Biochem. Suppls. 30/31:264-276, 1998. © 1998 Wiley-Liss, Inc.
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  • 79
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    Journal of Cellular Biochemistry 72 (1998), S. 313-336 
    ISSN: 0730-2312
    Keywords: Life and Medical Sciences ; Cell & Developmental Biology
    Source: Wiley InterScience Backfile Collection 1832-2000
    Topics: Biology , Chemistry and Pharmacology , Medicine
    Notes: No abstract.
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  • 80
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    Journal of Cellular Biochemistry 72 (1998), S. 338-340 
    ISSN: 0730-2312
    Keywords: Life and Medical Sciences ; Cell & Developmental Biology
    Source: Wiley InterScience Backfile Collection 1832-2000
    Topics: Biology , Chemistry and Pharmacology , Medicine
    Notes: No abstract.
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  • 81
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    Journal of Cellular Biochemistry 72 (1998), S. 304-311 
    ISSN: 0730-2312
    Keywords: DNA vaccines ; gene therapy ; vectors ; immune response ; antigen presentation ; Life and Medical Sciences ; Cell & Developmental Biology
    Source: Wiley InterScience Backfile Collection 1832-2000
    Topics: Biology , Chemistry and Pharmacology , Medicine
    Notes: Inoculations with antigen-expressing plasmid DNAs (DNA vaccines) in the production of protective immune responses. Since the initial development of DNA vaccines more than 5 years ago, major strides have been made in the design of efficient vaccine vectors and in the process of vaccine delivery. However, many questions remain regarding the mechanism of cellular transfection and in the development of immune responses. This review addresses functional aspects of DNA vaccines, including vector design and delivery, as well as cellular transfection and antigen presentation. J. Cell. Biochem. Suppls. 30/31:304-311, 1998. © 1998 Wiley-Liss, Inc.
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  • 82
    ISSN: 0730-2312
    Keywords: Ishikawa cells ; endometrium ; biotin ; multinucleated cells ; predomes ; domes ; pinopods ; Life and Medical Sciences ; Cell & Developmental Biology
    Source: Wiley InterScience Backfile Collection 1832-2000
    Topics: Biology , Chemistry and Pharmacology , Medicine
    Notes: Human Ishikawa endometrial cells form domes when confluent monolayers are stimulated with fresh fetal bovine serum. Extensive structural and biochemical changes have been detected during the approximately 30 h differentiation period. The earliest detectable change involves the formation of multinucleated structures and the appearance of “granules” that stain for biotin within those structures. Nuclei become associated with each other and are ultimately enclosed within a biotin-containing membrane. Aggregated membrane-sheathed nuclei and the cells containing them begin to elevate from the dish as biotin staining becomes apparent in apical membranes. The elevated structures are called predomes and consist of one or more very large cells containing the sheathed nuclei. Apical membranes of these unusual cells extend far out into the medium in structures that resemble endometrial pinopods. A lumen under the elevated cells fills with transcytosed fluid. As differentiation proceeds, highly concentrated chromatin material that was flattened against apical and lateral membranes of the predome cells begins to disperse. Small mononuclear cells evolve from larger predome cells. Apical membranes of predome and dome cells continue to stain for biotin. Gel electrophoresis of SDS-solubilized biotin-containing membranes, followed by Western blot analysis using avidin-linked peroxidase, resulted in three stained bands with molecular weights similar to those of the mitochondrial carboxylases: propionyl carboxylase, methylmalonyl carboxylase, and pyruvate carboxylase. J. Cell. Biochem. 71:400-415, 1998. © 1998 Wiley-Liss, Inc.
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  • 83
    ISSN: 0730-2312
    Keywords: opioids ; cathepsin D ; pS2 ; estrogen ; cancer ; Life and Medical Sciences ; Cell & Developmental Biology
    Source: Wiley InterScience Backfile Collection 1832-2000
    Topics: Biology , Chemistry and Pharmacology , Medicine
    Notes: In many cancer cell lines, including breast, prostate, lung, brain, head and neck, retina, and the gastrointestinal tract, opioids decrease cell proliferation in a dose-dependent and reversible manner. Opioid and/ or other neuropeptide receptors mediate this decrease. We report that only the steroid-hormone-sensitive cell lines MCF7 and T47D respond to opioid growth inhibition in a dose-dependent manner. Therefore, an interaction of the opioid and steroid receptor system might exist, as is the case with insulin. To investigate this interaction, we have assayed two estrogen-inducible proteins (pS2 and the lysosomal enzyme cathepsin D) in MCF7 and T47D cells. When cells were grown in the presence of FBS (in which case a minimal quantity of estrogens and/ or opioids is provided by the serum), we observed either no effect of etorphine or ethylketocyclazocine (EKC) or an increase of secretion and/ or production of pS2 and cathepsin D. However, when cells were cultured in charcoal-stripped serum and in the absence of phenol red, the effect of the two opioids is different: EKC decreased the production and/ or secretion of pS2 and cathepsin D, whereas etorphine increased their synthesis and/ or secretion. The differential effect of the two general opioids was attributed to their different receptor selectivity. Furthermore, the variations of the ratio of secreted/ produced protein and the use of cycloheximide indicate that opioids selectively modify the regulatory pathway of each protein discretely. In conclusion, through the interaction with opioid and perhaps other membrane-receptor sites, opioid agonists modify in a dose-dependent manner the production and the secretion of two estrogen-regulated proteins. Opioids may therefore disturb hormonal signals mediated by the estrogen receptors. Hence, these chemicals may have potential endocrine disrupting activities. J. Cell. Biochem. 71:416-428, 1998. © 1998 Wiley-Liss, Inc.
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  • 84
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    Keywords: Life and Medical Sciences ; Cell & Developmental Biology
    Source: Wiley InterScience Backfile Collection 1832-2000
    Topics: Biology , Chemistry and Pharmacology , Medicine
    Notes: Sackett RL, McCusker RH (1998): Multivalent cations depress ligand affinity of insulin-like growth factor-binding proteins-3 and -5 on human GM-10 fibroblast cell surfaces. J Cell Biochem 69:364-375.
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  • 85
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    Journal of Cellular Biochemistry 71 (1998), S. 479-490 
    ISSN: 0730-2312
    Keywords: macrophages ; antioxidant status ; NOD mice ; immunocytochemistry ; type 1 diabetes ; Life and Medical Sciences ; Cell & Developmental Biology
    Source: Wiley InterScience Backfile Collection 1832-2000
    Topics: Biology , Chemistry and Pharmacology , Medicine
    Notes: This study showed that citiolone (CIT), a free radical scavenger, significantly increased superoxide dismutase (P 〈 0.001 vs. untreated NOD, NMMA-treated, and silica-treated animals), catalase (P 〈 0.01 vs. untreated NOD), and glutathione peroxidase (P 〈 0.001 vs. untreated NOD and C57BL6/J) values. Silica treatment was capable of counteracting the plasma antioxidant capacity (TRAP) decrease observed in untreated NOD mice, although it did not block the blood glucose rise and insulitis progression in type 1 diabetes significantly. Conversely, early silica administration was able to deplete macrophages (as demonstrated by immunocytochemistry) and to block the rise in blood glucose levels and insulitis progression significantly. Silica-treated animals in this study showed the highest TRAP levels, demonstrating that depletion of macrophages also was able to improve the antioxidant status. This study suggested that macrophages are essential for type 1 diabetes development and showed that they also are involved when the antioxidant status is affected. The reported findings are significant in view of previous studies indicating that oxygen and/or nitrogen free radicals contribute to the islet β-cell destruction in type 1 diabetes animal models. J. Cell. Biochem. 71:479-490, 1998. © 1998 Wiley-Liss, Inc.
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  • 86
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    Keywords: proliferation ; maturation ; intracellular magnesium pools ; receptor-mediated stimuli ; cyclic-AMP ; IFN-α ; cell permeabilization ; ionophore A23187 ; Na-Mg antiporter ; Life and Medical Sciences ; Cell & Developmental Biology
    Source: Wiley InterScience Backfile Collection 1832-2000
    Topics: Biology , Chemistry and Pharmacology , Medicine
    Notes: Magnesium homeostasis in HL-60 promyelocytic leukemia cells was compared to that in neutrophyl-like HL-60 cells obtained by 1.3% DMSO treatment. Magnesium homeostasis was studied by the characterization of magnesium efflux, the identification of intracellular magnesium pools, and the regulation of intracellular ionized Mg2+. In both undifferentiated and neutrophyl-like HL-60 cells, magnesium efflux occurred via the Na-Mg antiporter which was inhibited by imipramine and stimulated by db cAMP and forskolin. Receptor-mediated signals such as ATP, IFN-α, or PGE1, which can trigger cAMP-dependent magnesium efflux, were ineffective in undifferentiated HL-60 cells but induced 60-70% increase of magnesium efflux in neutrophyl-like HL-60 cells. Selective membrane permeabilization by the cation ionophore A23187 induced a large magnesium release when cells were treated with rotenone. In both cell populations, the addition of glucose to rotenone-treated cells restored magnesium release to the control level. Permeabilization by 0.005% digitonin provoked the release of 90% cell total magnesium in both cell types. Intracellular [Mg2+]i was 0.15 and 0.26 mM in undifferentiated and neutrophyl-like HL-60 cells, respectively. Stimuli that triggered magnesium efflux, such as db cAMP in undifferentiated and IFN-α in neutrophyl-like HL-60 cells, induced a slow but consistent increase of [Mg2+]i which was independent from Ca2+movements. Overall, these data indicate that magnesium homeostasis is regulated by receptor-mediated magnesium efflux which was modified during differentiation of HL-60 cells. Stimulation of magnesium efflux is paralleled by an increase of [Mg2+]i which reflects a release of magnesium from the bound cation pool. J. Cell. Biochem. 71:441-448, 1998. © 1998 Wiley-Liss, Inc.
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  • 87
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    Journal of Cellular Biochemistry 71 (1998), S. 491-501 
    ISSN: 0730-2312
    Keywords: diabetic microangiopathy ; endothelium ; HMEC-1 ; Life and Medical Sciences ; Cell & Developmental Biology
    Source: Wiley InterScience Backfile Collection 1832-2000
    Topics: Biology , Chemistry and Pharmacology , Medicine
    Notes: Diabetic microangiopathy has been implicated as a fundamental feature of the pathological complications of diabetes including retinopathy, neuropathy, and diabetic foot ulceration. However, previous studies devoted to examining the deleterious effects of elevated glucose on the endothelium have been performed largely in primary cultured cells of macrovessel origin. Difficulty in the harvesting and maintenance of microvascular endothelial cells in culture have hindered the study of this relevant population. Therefore, the objective of this study was to characterize the effect of elevated glucose on the proliferation and involved signaling pathways of an immortalized human dermal microvascular endothelial cell line (HMEC-1) that possess similar characteristics to their in vivo counterparts. Human dermal microvascular endothelial cells (HMEC-1) were grown in the presence of normal (5 mM) or high D-glucose (20 mM) for 14 days. The proliferative response of HMEC-1 was compared under these conditions as well as the cAMP and PKC pathways by in vitro assays. Elevated glucose significantly inhibited (P 〈 0.05) HMEC-1 proliferation after 7, 10, and 14 days. This effect was not mimicked by 20 mM mannitol. The antiproliferative effect was more pronounced with longer exposure (1-14 days) to elevated glucose and was irreversible 4 days after a 10-day exposure. The antiproliferative effect was partially reversed in the presence of a PKA inhibitor, Rp-cAMP (10-50 μM), and/or a PKC inhibitor, Calphostin C (10 nM). HMEC-1 exposed to elevated glucose (20 mM) for 14 days caused an increase in cyclic AMP accumulation, PKA, and PKC activity but was not associated with the activation of downstream events such as CRE and AP-1 binding activity. These data support the hypothesis that HMEC-1 is a suitable model to study the deleterious effects of elevated glucose on microvascular endothelial cells. Continued studies with HMEC-1 may prove advantageous in delineation of the molecular pathophysiology associated with diabetic microangiopathy. J. Cell. Biochem. 71:491-501, 1998. © 1998 Wiley-Liss, Inc.
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  • 88
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    Journal of Cellular Biochemistry 72 (1998), S. 1-7 
    ISSN: 0730-2312
    Keywords: S phase ; DNA replication ; gene replication ; Life and Medical Sciences ; Cell & Developmental Biology
    Source: Wiley InterScience Backfile Collection 1832-2000
    Topics: Biology , Chemistry and Pharmacology , Medicine
    Notes: Events in the S phase of the cell cycle have been investigated to a relatively limited extent in comparison with those in G1 and M phases. Four aspects of S are briefly discussed in this report: (1) the final biochemical step permitting initiation of DNA synthesis, (2) determination of replication timing of individual genes and its mechanism, (3) S phase processes that lead to the onset of M phase, and (4) resetting the S-phase machinery. J. Cell. Biochem. Suppls. 30/31:1-7, 1998. © 1999 Wiley-Liss, Inc.
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  • 89
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    Journal of Cellular Biochemistry 71 (1998), S. 577-583 
    ISSN: 0730-2312
    Keywords: hsp70 ; translation ; heat shock proteins ; stress response ; restimulation ; feedback inhibition ; Life and Medical Sciences ; Cell & Developmental Biology
    Source: Wiley InterScience Backfile Collection 1832-2000
    Topics: Biology , Chemistry and Pharmacology , Medicine
    Notes: To develop an alternative to hyperthermia for the induction of hsp70 for presurgical cytoprotection, we investigated the optimal exposure conditions for magnetic field induction of hsp70. Normal human breast cells (HTB124) were exposed to 60-Hz magnetic fields and hsp70 levels were measured following three different exposure conditions: continuous exposure up to 3 h, a single 20-min exposure, and a single 20-min exposure followed by repeated 20-min exposures at different field strengths. In cells exposed continuously for 3 h, hsp70 levels peaked (46%) within 20 min and returned to control levels by 2 h. Following a single 20-min exposure, the return of hsp70 levels to control values extended to more than 3 h. When cells underwent a 20-min exposure followed by repeated 20-min exposures (restimulation) with different field strengths, additional increases in hsp70 levels were induced: 31% at 1 h, 41% at 2 h, and 30% at 3 h. J. Cell. Biochem. 71:577-583, 1998. © 1998 Wiley-Liss, Inc.
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  • 90
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    Journal of Cellular Biochemistry 72 (1998), S. iv 
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    Keywords: Life and Medical Sciences ; Cell & Developmental Biology
    Source: Wiley InterScience Backfile Collection 1832-2000
    Topics: Biology , Chemistry and Pharmacology , Medicine
    Notes: No abstract.
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  • 91
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    Journal of Cellular Biochemistry 72 (1998), S. 137-146 
    ISSN: 0730-2312
    Keywords: G proteins ; signal transduction ; protein tyrosine kinases ; PMN ; Life and Medical Sciences ; Cell & Developmental Biology
    Source: Wiley InterScience Backfile Collection 1832-2000
    Topics: Biology , Chemistry and Pharmacology , Medicine
    Notes: Complex cellular responses involve the integration of heterotrimeric G protein systems with protein kinase signal transduction pathways. Key in this integration is the control of small GTP-binding proteins including Ras and Rho family members. In this paper, we discuss the control of signal transduction pathways by G proteins and their integration with specific tyrosine kinases. The integration of G proteins, kinases, and small GTP-binding proteins in controlling cellular responses is illustrated through the newly defined Gα12/13-regulated pathways. Furthermore, the polymorphonuclear leukocyte provides a primary cell system for analyzing the integration of G proteins, kinases, and small GTP-binding proteins in controlling cellular functions such as superoxide production, adherence, chemotaxis, and granule secretion. J. Cell. Biochem. Suppls. 30/31:137-146, 1998. © 1998 Wiley-Liss, Inc.
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  • 92
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    Journal of Cellular Biochemistry 72 (1998), S. 158-167 
    ISSN: 0730-2312
    Keywords: peroxisomes ; lipid metabolism ; H2O2 metabolism ; Life and Medical Sciences ; Cell & Developmental Biology
    Source: Wiley InterScience Backfile Collection 1832-2000
    Topics: Biology , Chemistry and Pharmacology , Medicine
    Notes: Gene targeting and the elucidation of mutations underlying inherited peroxisomal diseases have provided new insights in peroxisomal lipid metabolism in vivo. The work led to the identification of a novel peroxisomal β-oxidation pathway and established clearly that genes, which are required for efficient peroxisomal oxidation of fatty acids, at the same time are key regulators of PPARα function in vivo. The new mouse models may provide helpful tools in the search for unknown natural PPARα agonists and in screening for in vivo PPARα antagonists. J. Cell Biochem. Suppls. 30/31:158-167, 1998. © 1998 Wiley-Liss, Inc.
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  • 93
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    Journal of Cellular Biochemistry 72 (1998), S. 147-157 
    ISSN: 0730-2312
    Keywords: LPA ; S1P ; G protein ; intracellular signaling pathways ; Edg receptors ; Life and Medical Sciences ; Cell & Developmental Biology
    Source: Wiley InterScience Backfile Collection 1832-2000
    Topics: Biology , Chemistry and Pharmacology , Medicine
    Notes: Lysophosphatidic acid (LPA) and sphingosine 1-phosphate (S1P) are potent phospholipid mediators with diverse biological activities. Their appearance and functional properties suggest possible roles in development, wound healing, and tissue regeneration. The growth-stimulating and other complex biological activities of LPA and S1P are attributable in part to the activation of multiple G protein-mediated intracellular signaling pathways. Several heterotrimeric G proteins, as well as Ras- and Rho-dependent pathways play central roles in the cellular responses to LPA and S1P. Recently, several G protein-coupled receptors encoded by a family of endothelial differentiation genes (edg) have been shown to bind LPA or S1P and transduce responses of cAMP, Ca2+, MAP kinases, Rho, and gene transcription. This review summarizes our current understanding of signaling pathways critical for cellular responses to LPA and S1P and of recent progress in the molecular biological analyses of the Edg receptors. J. Cell. Biochem. Suppls. 30/31:147-157, 1998. © 1998 Wiley-Liss, Inc.
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  • 94
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    Journal of Cellular Biochemistry 71 (1998), S. 515-523 
    ISSN: 0730-2312
    Keywords: binding ; complex formation ; retinoic X receptor ; TFIIB ; vitamin D receptor ; VDRE ; steroid receptor ; nuclear extract ; Life and Medical Sciences ; Cell & Developmental Biology
    Source: Wiley InterScience Backfile Collection 1832-2000
    Topics: Biology , Chemistry and Pharmacology , Medicine
    Notes: The vitamin D receptor (VDR) elicits a transcriptional response to 1,25-dihydroxyvitamin D3 by binding to specific response elements (VDRE) in the promoter of target genes. Retinoic X receptor (RXR) is required for formation of the VDR-VDRE complex when VDR is supplied at physiologic concentrations. When porcine intestinal nuclear extract is used as a source of VDR, two distinct complexes are always observed with native gel electrophoresis. Both complexes contain VDR and RXR. We now show that the faster-migrating complex requires another heretofore unknown nuclear factor for its formation. In addition, we provide evidence that the formation of the slower-migrating complex is enhanced by transcription factor IIB (TFIIB). Using ligand binding assays, we determined that both complexes contain the same ratio of VDR to VDRE. Using RXR subtype-specific antibodies in gel shift assays, we show that the complexes contain more than one RXR subtype. Therefore, the present results demonstrate VDR-RXR-VDRE complexes formed with pig intestinal nuclear extracts contain other proteins and that the complexes formed between VDR and VDRE are not simply heterodimers of VDR and RXR. J. Cell. Biochem. 71:515-523, 1998. © 1998 Wiley-Liss, Inc.
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  • 95
    ISSN: 0730-2312
    Keywords: intestinal epithelium ; cell growth ; cell differentiation ; HIEC ; Caco-2 ; Life and Medical Sciences ; Cell & Developmental Biology
    Source: Wiley InterScience Backfile Collection 1832-2000
    Topics: Biology , Chemistry and Pharmacology , Medicine
    Notes: The integrin α9β1 is one of the recently identified integrins whose expression is restricted to specialized tissues. Its exact function is still unknown. In the present study, we have analyzed the expression of the α9 subunit in human fetal and adult small intestinal and colonic epithelia as well as in intestinal cell lines by indirect immunofluorescence, immunoprecipitation, Western blot, and Northern blot. In intact tissues, the antigen was restricted to the basolateral domain of epithelial cells in intestinal crypts at the fetal stage and was absent in the adult. The α9β1 integrin was also detected in the intestinal cell lines HIEC-6 and Caco-2/15. The presence of α9β1 in HIEC-6 was found to be consistent with their proliferative crypt-like status. In Caco-2/15 cells, the integrin was present at high levels in proliferating cells but was downregulated when cells cease to grow and undertake their differentiation. EGF treatment, which is known to maintain Caco-2/15 cells in a proliferative state, resulted in higher levels of α9 as compared to control cells. Taken together, these observations suggest a relation between integrin α9β1 expression and proliferation in human intestinal cells. J. Cell. Biochem. 71:536-545, 1998. © 1998 Wiley-Liss, Inc.
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  • 96
    ISSN: 0730-2312
    Keywords: matrix metalloproteinase ; sea urchin ; development ; Life and Medical Sciences ; Cell & Developmental Biology
    Source: Wiley InterScience Backfile Collection 1832-2000
    Topics: Biology , Chemistry and Pharmacology , Medicine
    Notes: We have purified and characterized a collagenase/gelatinase activity expressed during sea urchin embryonic development. The native molecular mass was determined to be 160 kDa, while gelatin substrate gel zymography revealed an active species of 41 kDa, suggesting that the native enzyme is a tetramer of active subunits. Incubation in the presence of EGTA resulted in nearly complete loss of activity and this effect could be reversed by calcium. Calcium-induced reactivation appeared to be cooperative and occurred with an apparent kd value of 3.7 mM. Two modes of calcium binding to the 41-kDa subunit were detected; up to 80 moles of calcium bound with a kd value of 0.5 mM, while an additional 120 moles bound with a kd value of 5 mM. Amino acid analysis revealed a carboxy plus carboxyamide content of 24.3 mol/100 mol, indicating the availability of substantial numbers of weak Ca2+-binding sites. Calcium binding did not result in either secondary or quaternary structural changes in the collagenase/gelatinase, suggesting that Ca2+ may facilitate activation through directly mediating the binding of substrate to the enzyme. The collagenase/gelatinase activity was detected in blastocoelic fluid and in the hyalin fraction dissociated from 1-h-old embryos. Immunolocalization studies revealed two storage compartments in the egg; cortical granules and small granules/vesicles dispersed throughout the cytoplasm. After fertilization, the antigen was detected in both the apical and basal extracellular matrices, the hyaline layer, and basal lamina, respectively. J. Cell. Biochem. 71:546-558, 1998. © 1998 Wiley-Liss, Inc.
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  • 97
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    Journal of Cellular Biochemistry 71 (1998), S. 524-535 
    ISSN: 0730-2312
    Keywords: caveolae ; caveolin-1 ; tyrosine kinase ; cell transformation ; Life and Medical Sciences ; Cell & Developmental Biology
    Source: Wiley InterScience Backfile Collection 1832-2000
    Topics: Biology , Chemistry and Pharmacology , Medicine
    Notes: Members of the nonreceptor tyrosine kinase family appear to be targeted to caveolae membrane. We have used a Rat-1 cell expressing a temperature sensitive pp60v-src kinase to assess the initial changes that take place in caveolae after kinase activation. Within 24-48 h after cells were shifted to the permissive temperature, a set of caveolae-specific proteins became phosphorylated on tyrosine. During this period there was a decline in the caveolae marker protein, caveolin-1, a loss of invaginated caveolae, and a 70% decline in the sphingomyelin content of the cell. One of the phosphorylated proteins was caveolin-1 but it was associated in coimmunoprecipitation assays with both a 30 kDa and a 27 kDa tyrosine-phosphorylated protein. Finally, the cells changed from having a typical fibroblast morphology to a rounded shape lacking polarity. In light of the recent evidence that diverse signaling events originate from caveolae, pp60v-src kinase appears to cause global changes to this membrane domain that might directly contribute to the transformed phenotype. J. Cell. Biochem. 71:524-535, 1998. © 1998 Wiley-Liss, Inc.
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  • 98
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    Journal of Cellular Biochemistry 71 (1998), S. 559-568 
    ISSN: 0730-2312
    Keywords: plasma cell ; CD19 ; CD38 ; naphthol AS-D chloroacetate esterase ; B cells ; Life and Medical Sciences ; Cell & Developmental Biology
    Source: Wiley InterScience Backfile Collection 1832-2000
    Topics: Biology , Chemistry and Pharmacology , Medicine
    Notes: This study demonstrates that the multiple myeloma cell (MMC) in its plasma cell form is morphologically indistinguishable from human osteoclast-like cells that form in culture when peripheral blood mononuclear cells (PBMCs) are plated at high density in serum containing medium. MM has been described as a disease of B-cell lineage, monoclonal immunoglobulin (Ig) producing cells with unique properties: MM precursor cells lodge in bone, where they proliferate and differentiate into plasma cell tumors. Then, by some mechanism, presumably involving cytokines, these cells mediate an increase in neighboring osteoclast numbers and activity, leading to excessive bone erosion and hypercalcemia. Three days after plating PBMCs, tartrate resistant acid phosphatase- (TRAP-) blasts as well as TRAP+ cells, each with an eccentric nucleus, appear in culture. By day 10, TRAP+, vitronectin+ (VR+) cells, appear to be morphologically indistinguishable from multiple myeloma plasma cells (MMPCs) on cytocentrifuge preparations. These cells are CD19- and CD38++, as are MMCs reported by others. Other surface markers are also shared. Furthermore, Ig mRNA is demonstrated in the cytoplasm of cells at 8 days by in situ hybridization with the IgG FcA3 sequence. This novel finding is not unusual, in light of reports, demonstrating non-B-lineage Ig-producing cells. Thus, this study raises some serious questions about the true nature of MMCs. J. Cell. Biochem. 71:559-568, 1998. © 1998 Wiley-Liss, Inc.
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  • 99
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    Journal of Cellular Biochemistry 71 (1998), S. 569-576 
    ISSN: 0730-2312
    Keywords: regucalcin ; calmodulin ; protein kinase ; calcium-binding protein ; liver nuclei ; regenerating rat liver ; Life and Medical Sciences ; Cell & Developmental Biology
    Source: Wiley InterScience Backfile Collection 1832-2000
    Topics: Biology , Chemistry and Pharmacology , Medicine
    Notes: The effect of Ca2+-binding protein regucalcin on protein kinase activity in the nuclei of normal and regenerating rat livers was investigated. Protein kinase activity in the nuclei isolated from normal rat liver was significantly increased by addition of Ca2+ (500 μM) and calmodulin (10 μg/ml) in the enzyme reaction mixture. Nuclear protein kinase activity was significantly decreased in the presence of EGTA (1.0 mM), trifluoperazine (TFP; 20 μM), dibucaine (10-4 M), or staurosporine (10-7 M), indicating that Ca2+-dependent protein kinases are present in the nuclei. Protein kinase activity was significantly elevated in the liver nuclei obtained at 6 to 48 h after a partial hepatectomy. Hepatectomy-increased nuclear protein kinase activity was significantly decreased in the presence of EGTA (1.0 mM), TFP (20 μM), or staurosporine (10-7 M) in the enzyme reaction mixture. The presence of regucalcin (0.1-0.5 μM) caused a significant decrease in protein kinase activity in the nuclei obtained from normal and regenerating rat livers. Meanwhile, the nuclear protein kinase activity from normal and regenerating livers was significantly elevated in the presence of anti-regucalcin monoclonal antibody (50-200 ng/ml). The present study suggests that regucalcin plays a role in the regulation of protein kinase activity in the nuclei of proliferative liver cells. J. Cell. Biochem. 71:569-576, 1998. © 1998 Wiley-Liss, Inc.
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  • 100
    Electronic Resource
    Electronic Resource
    New York, N.Y. : Wiley-Blackwell
    Journal of Cellular Biochemistry 72 (1998), S. 18-29 
    ISSN: 0730-2312
    Keywords: mammalian DNA replication fork ; DNA synthesome ; PCNA ; Life and Medical Sciences ; Cell & Developmental Biology
    Source: Wiley InterScience Backfile Collection 1832-2000
    Topics: Biology , Chemistry and Pharmacology , Medicine
    Notes: The process of DNA replication in mammalian cells is highly complex and has several unique features that distinguish it from simpler prokaryotic systems. The study of mammalian DNA replication lagged behind that of prokaryotes for many years. This was because of the lack of a reliable and efficient mammalian cell-based in vitro DNA replication system. In 1984, the first mammalian-based DNA replication system that initiated DNA synthesis successfully in vitro was developed. The employment of the mammalian in vitro DNA replication system has led to the identification of several DNA replication proteins. This article describes the current knowledge regarding the proteins mediating mammalian DNA replication, as well as how they are proposed to function during DNA synthesis. There is also a discussion of the role the mammalian cell nuclear architecture plays in DNA replication. The evidence for the existence of an organized DNA replication machine in mammalian cells is also presented. J. Cell. Biochem. Suppls. 30/31:18-29, 1998. © 1998 Wiley-Liss, Inc.
    Additional Material: 3 Ill.
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