bluuebunny/crossref_metadata_2025 huggingface dataset:
Epstein-Barr Virus (EBV)-Encoded RNA 2 (EBER2) but Not EBER1 Plays a Critical Role in EBV-Induced B-Cell Growth Transformation
Authors: Wu Yi , Maruo Seiji , Yajima Misako , Kanda Teru , Takada Kenzo
Published: August 2007

Epstein-Barr virus (EBV)-encoded RNA 1 (EBER1) and EBER2 are untranslated RNAs and the most abundant viral transcripts in latently EBV-infected cells. We previously reported that EBERs play a critical role in efficient EBV-induced growth transformation of primary B cells. To investigate whether EBER1 and EBER2 have distinct roles in B-cell growth transformation, recombinant EBVs carrying either EBER1 or EBER2 were generated. The transforming ability of recombinant EBVs expressing EBER2 was as high as that of EBVs expressing both EBER1 and EBER2. In contrast, the transforming ability of recombinant EBVs carrying EBER1 was impaired and was similar to that of EBV lacking both EBER1 and EBER2. Lymphoblastoid cell lines (LCLs) established with EBVs carrying EBER2 proliferated at low cell densities, while LCLs established with EBVs carrying EBER1 did not. Interleukin 6 (IL-6) production in LCLs expressing EBER2 was more abundant than in those lacking EBER2. The growth of LCLs lacking EBER2 was enhanced by the addition of recombinant IL-6 to the cell culture, while the growth of EBER2-expressing LCLs was inhibited by a neutralizing anti-IL-6 antibody. These results demonstrate that EBER2, but not EBER1, contributes to efficient B-cell growth transformation. We conclude that EBER1 and EBER2, despite their structural similarity, have different functions in latently infected lymphoblastoid cells.
Symptomatic and Asymptomatic Viral Recrudescence in Solid-Organ Transplant Recipients and Its Relationship with the Antigen-Specific CD8
+
T-Cell Response
Authors: Crough Tania , Fazou Chrysa , Weiss Julissa , Campbell Scott , Davenport Miles P. , Bell Scott C. , Galbraith Andrew , McNeil Keith , Khanna Rajiv
Published: August 2007

Using ex vivo antigen-specific T-cell analysis, we found that symptomatic cytomegalovirus recrudescence in transplant recipients was coincident with reduced expression of gamma interferon (IFN-γ) by virus-specific CD8
+
T cells and an up-regulation of CD38 expression on these T cells, although there was no significant change in the absolute number of virus-specific cells (as assessed by major histocompatibility complex-peptide multimers). In contrast, HLA class I-matched transplant patients with asymptomatic viral recrudescence showed increased expansion of antigen-specific T cells and highly stable IFN-γ expression by epitope-specific T cells. These studies suggest that a strong functional T-cell response plays a crucial role in defining the clinical outcome of acute viral recrudescence.
Inhibition of Transfer to Secondary Receptors by Heparan Sulfate-Binding Drug or Antibody Induces Noninfectious Uptake of Human Papillomavirus
Authors: Selinka Hans-Christoph , Florin Luise , Patel Hetal D. , Freitag Kirsten , Schmidtke Michaela , Makarov Vadim A. , Sapp Martin
Published: August 2007

Infection with various human papillomaviruses (HPVs) induces cervical cancers. Cell surface heparan sulfates (HS) have been shown to serve as primary attachment receptors, and molecules with structural similarity to cell surface HS, like heparin, function as competitive inhibitors of HPV infection. Here we demonstrate that the
N
,
N
′-bisheteryl derivative of dispirotripiperazine, DSTP27, efficiently blocks papillomavirus infection by binding to HS moieties, with 50% inhibitory doses of up to 0.4 μg/ml. In contrast to short-term inhibitory effects of heparin, pretreatment of cells with DSTP27 significantly reduced HPV infection for more than 30 h. Using DSTP27 and heparinase, we furthermore demonstrate that HS moieties, rather than laminin 5, present in the extracellular matrix (ECM) secreted by keratinocytes are essential for infectious transfer of ECM-bound virions to cells. Prior binding to ECM components, especially HS, partially alleviated the requirement for cell surface HS. DSTP27 blocks infection by cell-bound virions by feeding into a noninfectious entry pathway. Under these conditions, virus colocalized with HS moieties in endocytic vesicles. Similarly, postattachment treatment of cells with heparinase, cytochalasin D, or neutralizing antibodies resulted in uptake of virions without infection, indicating that deviation into a noninfectious entry pathway is a major mode of postattachment neutralization. In untreated cells, initial colocalization of virions with HS on the cell surface and in endocytic vesicles was lost with time. Our data suggest that initial attachment of HPV to HS proteoglycans (HSPGs) must be followed by secondary interaction with additional HS side chains and transfer to a non-HSPG receptor for successful infection.
Sheeppox Virus Kelch-Like Gene
SPPV-019
Affects Virus Virulence
Authors: Balinsky C. A. , Delhon G. , Afonso C. L. , Risatti G. R. , Borca M. V. , French R. A. , Tulman E. R. , Geary S. J. , Rock D. L.
Published: August 2007

Sheeppox virus (SPPV), a member of the
Capripoxvirus
genus of the
Poxviridae
, is the etiologic agent of a significant disease of sheep in the developing world. Genomic analysis of pathogenic and vaccine capripoxviruses identified genes with potential roles in virulence and host range, including three genes with similarity to kelch-like genes of other poxviruses and eukaryotes. Here, a mutant SPPV with a deletion in the
SPPV-019
kelch-like gene, ΔKLP, was derived from the pathogenic strain SPPV-SA. ΔKLP exhibited in vitro growth characteristics similar to those of SPPV-SA and revertant virus (RvKLP). ΔKLP-infected cells exhibited a reduction in Ca
2+
-independent cell adhesion, suggesting that
SPPV-019
may modulate cellular adhesion. When inoculated in sheep by the intranasal or intradermal routes, ΔKLP was markedly attenuated, since all ΔKLP-infected lambs survived infection. In contrast, SPPV-SA and RvKLP induced mortality approaching 100%. Lambs inoculated with ΔKLP exhibited marked reduction or delay in fever response, gross lesions, viremia, and virus shedding compared to parental and revertant viruses. Together, these findings indicate that
SPPV-019
is a significant SPPV virulence determinant in sheep.
Pseudorabies Virus Us9 Directs Axonal Sorting of Viral Capsids
Authors: Lyman M. G. , Feierbach B. , Curanovic D. , Bisher M. , Enquist L. W.
Published: August 2007

Pseudorabies virus (PRV) mutants lacking the Us9 gene cannot spread from presynaptic to postsynaptic neurons in the rat visual system, although retrograde spread remains unaffected. We sought to recapitulate these findings in vitro using the isolator chamber system developed in our lab for analysis of the transneuronal spread of infection. The wild-type PRV Becker strain spreads efficiently to postsynaptic neurons in vitro, whereas the Us9-null strain does not. As determined by indirect immunofluorescence, the axons of Us9-null infected neurons do not contain the glycoproteins gB and gE, suggesting that their axonal sorting is dependent on Us9. Importantly, we failed to detect viral capsids in the axons of Us9-null infected neurons. We confirmed this observation by using three different techniques: by direct fluorescence of green fluorescent protein-tagged capsids; by transmission electron microscopy; and by live-cell imaging in cultured, sympathetic neurons. This finding has broad impact on two competing models for how virus particles are trafficked inside axons during anterograde transport and redefines a role for Us9 in viral sorting and transport.
Crystal Structure and Structural Mechanism of a Novel Anti-Human Immunodeficiency Virus andd-Amino Acid-Containing Chemokine
Authors: Liu Dongxiang , Madani Navid , Li Ying , Cao Rong , Choi Won-Tak , Kawatkar Sameer P. , Lim Mi Youn , Kumar Santosh , Dong Chang-Zhi , Wang Jun , Russell Julie D. , Lefebure Caroline R. , An Jing , Wilson Scott , Gao Yi-Gui , Pallansch Luke A. , Sodroski Joseph G. , Huang Ziwei
Published: August 2007

Chemokines and their receptors play important roles in normal physiological functions and the pathogeneses of a wide range of human diseases, including the entry of human immunodeficiency virus type 1 (HIV-1). However, the use of natural chemokines to probe receptor biology or to develop therapeutic drugs is limited by their lack of selectivity and the poor understanding of mechanisms in ligand-receptor recognition. We addressed these issues by combining chemical and structural biology in research into molecular recognition and inhibitor design. Specifically, the concepts of chemical biology were used to develop synthetically and modularly modified (SMM) chemokines that are unnatural and yet have properties improved over those of natural chemokines in terms of receptor selectivity, affinity, and the ability to explore receptor functions. This was followed by using structural biology to determine the structural basis for synthetically perturbed ligand-receptor selectivity. As a proof-of-principle for this combined chemical and structural-biology approach, we report a noveld-amino acid-containing SMM-chemokine designed based on the natural chemokine called viral macrophage inflammatory protein II (vMIP-II). The incorporation of unnaturald-amino acids enhanced the affinity of this molecule for CXCR4 but significantly diminished that for CCR5 or CCR2, thus yielding much more selective recognition of CXCR4 than wild-type vMIP-II. Thisd-amino acid-containing chemokine also showed more potent and specific inhibitory activity against HIV-1 entry via CXCR4 than natural chemokines. Furthermore, the high-resolution crystal structure of thisd-amino acid-containing chemokine and a molecular-modeling study of its complex with CXCR4 provided the structure-based mechanism for the selective interaction between the ligand and chemokine receptors and the potent anti-HIV activity ofd-amino acid-containing chemokines.
Radiometric dating of Late Precambrian times
Authors: Odin G. S. , Gale N. H. , Doré F.
Published: August 2007

Between about 1979 and 1981 new radiometric data relevant to the numerical age of the Precambrian-Cambrian boundary became available. Based on this it was suggested in a recent review (Odin
et al.
1983) that the numerical age for that boundary was probably much younger than usually accepted, lying probably in the interval of time 520-540 Ma rather than at about 580-600 Ma. This new estimate has provoked discussions which essentially concern the stratigraphical location appropriate to these modern dates. In addition, it has been argued that this new view of the location of the Precambrian-Cambrian boundary did not take into account all the available geochronological results. We consider this last remark as unfounded at the time when our review was submitted for publication (at the beginning of 1982). However, one result of our review seems to have been to rejuvenate interest in the subject so that there is now more data to be discussed. Although the scarcity of fully published results still permits one at present only to propose tentative conclusions, some facts seem well enough established; conversely, in our opinion, other data are certainly not as soundly based as some authors aver. The present comment tries to give complementary information to enable others to judge both our own arguments as well as those of our colleagues.

A fundamental new contribution to this problem is in progress, i.e. a formal definition of the Precambrian-Cambrian boundary within the Meishucun stage of China (apparently now strongly advocated by the IUGS-IGCP Working Group
Remarks on the numerical scale of Ordovician to Devonian times
Authors: Odin G. S.
Published: August 2007

The Early Palaeozoic is the most difficult portion of the time-scale to calibrate due to the low number of precise calibration points although knowledge has greatly increased during the last few years. Thus, two-thirds of the data selected by McKerrow
et al.
(this volume) had not been published in 1980. These new data permit a reassessment of the preceding proposals. The location of some boundaries is still somewhat subjective; this explains differences in recommended or preferred numbers proposed by different authors. However, the correct assessment of the available data by the different authors allow one to define
intervals of time
(better than just numbers), and some sort of 'non disagreement' is now obtained which was not the case earlier. The present comment intends to show the points of agreement, to underline some differences of interpretation, and discuss some data not considered by McKerrow
et al.
Comments on the geochronology of the Carboniferous to Triassic times
Authors: Odin G. S.
Published: August 2007

Thanks to the relatively numerous and more or less reliable radiometric dates obtained from the Carboniferous to Triassic sequences it is possible to choose the best calibration points before trying to draw a picture of the corresponding numerical time-scale. In this context, the analysis of Forster & Warrington in the introduction to their chapter is a most welcome reminder of the criteria for data selection, sometimes neglected or forgotten by other authors.

Taking this into account, one may be sure that the portion of the time-scale proposed is probably one of the most objectively founded in this book for: (1) The authors are fully aware of the various uncertainties arising in the exercise of assessing a calibration point. (2) They actually use their own recommendations, when possible, and try to discuss each of the different areas of uncertainty (i.e.) the stratigraphical and the geochemical as well as the analytical ones in order to weight the reliability of a given date. (3) They have found in the literature a large number of data from which they selected 45. These are supported by other results which, although only briefly mentioned and less significant, are useful to reinforce their arguments.

The result of this considerable work is a time-scale which certainly is a very good reference. The minor remarks proposed here must be considered therefore as a modest complement of information to emphasize some of the limited differences between this work and the synthesis edited by the author in 1982 (Odin 1982).
Concerning the numerical ages proposed for the Jurassic and Cretaceous geochronology
Authors: Odin G. S.
Published: August 2007

In the presentation by Drs Hallam and Hancock some numbers are proposed to calibrate the Middle and Late Mesozoic time. For this period some (if not all) stage boundaries are actually not precisely located from a purely stratigraphical point of view, and, strictly speaking, no definitive numbers can be assigned to them. Consequently, different acceptable solutions can be proposed concerning the numerical age of these boundaries. However, some considerations developed by Hallam and Hancock do not correspond to the present state of knowledge resulting, in my view, in either incomplete or sometimes obsolete conclusions. These considerations are discussed below.
The Neogene: Part 2 Neogene geochronology and chronostratigraphy
Authors: Berggren W. A. , Kent D. V. , van Couvering J. A.
Published: August 2007

We present a revised Neogene geochronology based upon a best fit to selected high temperature radiometric dates on a number of identified magnetic polarity chrons (within the late Cretaceous, Paleogene, and Neogene) which minimizes apparent accelerations in sea-floor spreading. An assessment of first order correlations of calcareous plankton biostratigraphic datum events to magnetic polarity stratigraphy yields the following estimated magnetobiochronology of major chronostratigraphic boundaries: Oligocene/Miocene (Chron C6CN): 23.7 Ma; Miocene/Pliocene (slightly younger than Gilbert/Chron 5 boundary): 5.3 Ma; Pliocene/Pleistocene (slightly younger than Olduvai Subchron): 1.6 Ma.

Changes to the marine time-scale are relatively minor in terms of recent and current usage except in the interval of the middle Miocene where new DSDP data reveal that previous correlations of magnetic anomalies 5 and 5A to magnetic polarity Chrons 9 and 11, respectively, are incorrect. Our revized magnetobiostratigraphic correlations result in a 1.5-2 m.y. shift towards younger magnetobiochronologic age estimate in the middle Miocene. Radiometric dates correlated to bio- and magnetostratigraphy in continental section generally support the revized marine magnetobiochronology presented here. Major changes, however, are made in marine-non-marine correlations in the Miocene in Eurasia which indicate African-Eurasian migrations through the Persian Gulf as early as 20 Ma. The 12.5 Ma estimate of theHippariondatum is supported by recent taxonomic revisions of the hipparions and magnetobiostratigraphic correlations which show that primitive hipparions first arrived in Eurasia and North Africa atc.12.5 Ma and a second wave in the tropics (i.e. Indian and central Africa) atc.10 Ma.
Sr isotopic constraints for the sedimentation rate of deep sea red clays in the southern Pacific Ocean
Authors: Clauer N. , Hoffert M.
Published: August 2007

Sedimentological, mineralogical, chemical and Rb-Sr isotopic studies were made on Fe-smectites (nontronites) from deep sea red clays taken from two cores located 100 km apart in the southern Pacific Ocean. They show that: (1) these sediments are authigenic, (2) they contain variable but few amounts of volcanic-derived chemical components, and (3) they were transported from some place in the ocean and deposited at the present-day site. The transportation, which could occur at different periods, was likely induced by the submarine topography and bottom currents.

These observations necessitate a reconsideration of the traditional concept of sedimentation rate for the red clay facies. Although exhibiting considerable similarities, these sediments may correspond to different stages of a submarine sedimentary cycle. A given horizon can therefore reflect a submarine pedological event, a sudden and massive accumulation, or a very low sedimentation of material formed elsewhere. Genetic information is necessary to determine the local sedimentation rates of red clay, and the inconstancy of the sedimentation prevents any generalization on an ocean-wide scale.
Geochronology in the Central Alps: dating of metamorphism, subsequent cooling with Oligocene glaciation, and the development of the recent landscape
Authors: Jäager E.
Published: August 2007

The first K-Ar and Rb-Sr measurements from the Central Alps immediately revealed that the measured age does not date the metamorphic mica formation but a later event. Samples from areas of simple geological relationship have been analysed to learn which parameters control the age results: biotites of post-metamorphic pegmatites from the Verzasca valley (Ticino) and from adjacent Verzasca gneiss yield identical Rb-Sr ages. The same is true for biotite flakes of 20 cm diameter from open fissures and fine grained biotite from the nearby gneiss. This means that Rb-Sr biotite ages cannot date the climax of the metamorphism nor a compression phase.

When mica ages are related to the Tertiary Lepontine metamorphism of the Central Alps, certain patterns in the regional age distribution can be observed when rocks of granitic composition are analysed:

1. pre-Lepontine-metamorphic Rb-Sr and K-Ar ages on biotites are found only in areas of low grade metamorphism, below the stilpnomelane stability;

2. a zone of intermediate biotite ages (between pre- and post-metamorphic ages) follows metamorphic isograds; for rocks of granitic composition the intermediate age zone corresponds to the zone of Alpine stilpnomelane. In resistant rocks, more basic rocks which are poor in fluid phases, such as pre-Alpine eclogites and granulites, pre-Alpine biotite ages are found, even in rocks from the zone of Alpine chloritoid;

3. within the area of Alpine staurolite only Alpine biotite ages are found, independent of the type of rock and the biotite grain size; within a certain region all samples from granites and
Isotopic and palaeomagnetic evidence for rates of cooling, uplift and erosion
Authors: Dodson M. H. , McClelland-Brown E.
Published: August 2007

The use of isotopic and magnetic blocking temperatures to infer cooling history is reviewed in the light of kinetic models of the blocking process. Published isotopic estimates of cooling and uplift (erosion) rates are based upon (a) vertical gradients of fission track ages, (b) age differences amongst isotopic-mineral systems with different blocking temperatures and (c) kinetic analysis of
39
Ar-
40
Ar step-heating experiments. The palaeomagnetic approach to cooling history depends upon thermal demagnetization experiments upon individual samples, from which different blocking temperatures can be assigned to different directions of magnetization having known age relationships. Successive magnetic reversals might in principle be used but only in areas of rapid postorogenic cooling. Where cooling is very slow it may be possible to use apparent polar wander paths to infer cooling rates, as in the mid-Proterozoic of West Greenland. Conversely, in the Grenville Province distinctive components of magnetization have been dated by reference to a cooling history based upon argon-39. In Scotland a study of imposed magnetizations in thermal aureoles of Tertiary dykes provided estimates of ambient temperature at the times at which they were intruded. Cooling (erosion) rates so derived vary bimodally from ~ 30°C (~ 1 km) per million years over periods of ~ 2 x 10
7
years immediately following orogeny, to ~ 1°C (~ 30 m) per million years in cratonic areas over periods of ~ 2 x 10
8
years, and broadly agree with sedimentological estimates.
An interim time-scale
Authors: Snelling N. J.
Published: August 2007

The time-scale presented here endeavours to take cognisance of the views expressed in the Symposium, those expressed in other recent publications, notably the reviews and collations of Odin (1982) and Harland
et al.
(1982; based on Armstrong 1978), and the suggestions of the Subcommission on Precambrian Stratigraphy (Sims 1980). The conclusions of the contributors to these various works are not always compatible and this scale involves elements of both compromise and personal judgement. No plus or minus figures have been assigned to the boundaries although estimates of the uncertainty to be attached to the boundaries are commonly to be found in the more recent literature. It should be emphasized that these uncertainties are generally expressions of the limits within which a particular boundary probably lies
according to the author concerned
, they are thus apt to be somewhat subjective.
Evolutionary Game Theory and Adaptive Dynamics of Continuous Traits
Authors: McGill Brian J. , Brown Joel S.
Published: August 2007

Continuous-trait game theory fills the niche of enabling analytically solvable models of the evolution of biologically realistically complex traits. Game theory provides a mathematical language for understanding evolution by natural selection. Continuous-trait game theory starts with the notion of an evolutionarily stable strategy (ESS) and adds the concept of convergence stability (that the ESS is an evolutionary attractor). With these basic tools in hand, continuous-trait game theory can be easily extended to model evolution under conditions of disruptive selection and speciation, nonequilibrium population dynamics, stochastic environments, coevolution, and more. Many models applying these tools to evolutionary ecology and coevolution have been developed in the past two decades. Going forward we emphasize the communication of the conceptual simplicity and underlying unity of ideas inherent in continuous-trait game theory and the development of new applications to biological questions.
The Maintenance of Outcrossing in Predominantly Selfing Species: Ideas and Evidence from Cleistogamous Species
Authors: Oakley Christopher G. , Moriuchi Ken S. , Winn Alice A.
Published: August 2007

Cleistogamous species present strong evidence for the stability of mixed mating, but are generally not considered in this context. Individuals of cleistogamous species produce both obligately selfing cleistogamous flowers (CL) and potentially outcrossed chasmogamous flowers (CH) with distinct morphologies. Greater energetic economy and reliability of CL relative to CH suggest that forces that maintain selection for outcrossing may be stronger in these species than in mixed maters with monomorphic flowers. We reviewed data from 60 studies of cleistogamous species to evaluate proposed explanations for the evolutionary stability of mixed cleistogamous and chasmogamous reproduction and to quantify the magnitude of selection necessary to account for the maintenance of CH. We found circumstantial support for existing hypotheses for the stability of cleistogamy, and that forces that maintain CH must account for a 15–342% advantage of reproduction via CL. We suggest that heterosis and the effects of mass action pollination should be considered.
Roles of wound geometry, wound size, and extracellular matrix in the healing response of bovine corneal endothelial cells in culture
Authors: Grasso Silvina , Hernández Julio A. , Chifflet Silvia
Published: August 2007

It has classically been accepted that the healing of narrow wounds in epithelia occurs by the formation of a contractile actin cable, while wide wounds are resurfaced by lamellipodia-dependent migration of border cells into the denuded area. To further investigate the general validity of this idea, we performed systematic experiments of the roles of wound geometry, wound size, and extracellular matrix (ECM) in wound healing in monolayers of bovine corneal endothelial cells, a system shown here to predominantly display any of the two healing mechanisms according to the experimental conditions. We found that, in this system, it is the absence or presence of the ECM on the wound surface that determines the specific healing mode. Our observations demonstrate that, independent of their size and geometry, wounds created maintaining the ECM heal by migration of cells into the wound area, while ECM removal from the wound surface determines the predominant formation of an actin cable. While the latter mechanism is slower, the actin cable permits the maintainance of the epithelial phenotype to a larger extent during the healing process, as also confirmed by our finding of a more conserved localization of cadherin and vinculin. We also introduce a model that simulates experimental findings about the dynamics of healing mechanisms, both for the maintenance or removal of the ECM on the wound surface. The findings of this study may contribute to the understanding of physiological and pathological aspects of epithelial wound healing and to the design of therapeutic strategies.
Edaravone mimics sphingosine-1-phosphate-induced endothelial barrier enhancement in human microvascular endothelial cells
Authors: Omori Kazuyoshi , Shikata Yasushi , Sarai Kei , Watanabe Naomi , Wada Jun , Goda Noriko , Kataoka Noriyuki , Shikata Kenichi , Makino Hirofumi
Published: August 2007

Edaravone is a potent scavenger of hydroxyl radicals and is quite successful in patients with acute cerebral ischemia, and several organ-protective effects have been reported. Treatment of human microvascular endothelial cells with edaravone (1.5 μM) resulted in the enhancement of transmonolayer electrical resistance coincident with cortical actin enhancement and redistribution of focal adhesion proteins and adherens junction proteins to the cell periphery. Edaravone also induced small GTPase Rac activation and focal adhesion kinase (FAK; Tyr576) phosphorylation associated with sphingosine-1-phosphate receptor type 1 (S1P1) transactivation. S1P1 protein depletion by the short interfering RNA technique completely abolished edaravone-induced FAK (Tyr576) phosphorylation and Rac activation. This is the first report of edaravone-induced endothelial barrier enhancement coincident with focal adhesion remodeling and cytoskeletal rearrangement associated with Rac activation via S1P1 transactivation. Considering the well-established endothelial barrier-protective effect of S1P, endothelial barrier enhancement as a consequence of S1P1 transactivation may at least partly be the potent mechanisms for the organ-protective effect of edaravone and is suggestive of edaravone as a therapeutic agent against systemic vascular barrier disorder.
Metabolic homeostasis in mice with disruptedClockgene expression in peripheral tissues
Authors: Kennaway David J. , Owens Julie A. , Voultsios Athena , Boden Michael J. , Varcoe Tamara J.
Published: August 2007

The role of peripheral vs. central circadian rhythms and Clock in the maintenance of metabolic homeostasis and with aging was examined by using ClockΔ19+MEL mice. These have preserved suprachiasmatic nucleus and pineal gland rhythmicity but arrhythmic Clock gene expression in the liver and skeletal muscle. ClockΔ19+MEL mice showed fasting hypoglycemia in young-adult males, fasting hyperglycemia in older females, and substantially impaired glucose tolerance overall. ClockΔ19+MEL mice had substantially reduced plasma insulin and plasma insulin/glucose nocturnally in males and during a glucose tolerance test in females, suggesting impaired insulin secretion. ClockΔ19+MEL mice had reduced hepatic expression and loss of rhythmicity of gck, pfkfb3, and pepck mRNA, which is likely to impair glycolysis and gluconeogenesis. ClockΔ19+MEL mice also had reduced glut4 mRNA in skeletal muscle, and this may contribute to poor glucose tolerance. Whole body insulin tolerance was enhanced in ClockΔ19+MEL mice, however, suggesting enhanced insulin sensitivity. These responses occurred although the ClockΔ19mutation did not cause obesity and reduced plasma free fatty acids while increasing plasma adiponectin. These studies on clock-gene disruption in peripheral tissues and metabolic homeostasis provide compelling evidence of a relationship between circadian rhythms and the glucose/insulin and adipoinsular axes. It is, however, premature to declare that clock-gene disruption causes the full metabolic syndrome.
Ventilatory chemosensitivity of the 1-day-old chicken hatchling after embryonic hypoxia
Authors: Szdzuy Kirsten , Mortola Jacopo P.
Published: August 2007

We investigated the effects of sustained embryonic hypoxia on the neonatal ventilatory chemosensitivity. White Leghorn chicken eggs were incubated at 38°C either in 21% O2throughout incubation (normoxia, Nx) or in 15% O2from embryonic day 5 (hypoxia, Hx), hatching time included. Hx embryos hatched ∼11 h later than Nx, with similar body weights. Measurements of gaseous metabolism (oxygen consumption, V̇o2) and pulmonary ventilation (V̇e) were conducted either within the first 8 h (early) or later hours (late) of the first posthatching day. In resting conditions, Hx had similar V̇o2and body temperature (Tb) and slightly higher V̇e and ventilatory equivalent (V̇e/V̇o2) than Nx. Ventilatory chemosensitivity was evaluated from the degree of hyperpnea (increase in V̇e) and of hyperventilation (increase in V̇e/V̇o2) during acute hypoxia (15 and 10% O2, 20 min each) and acute hypercapnia (2 and 4% CO2, 20 min each). The chemosensitivity differed between the early and late hours, and at either time the responses to hypoxia and hypercapnia were less in Hx than in Nx because of a lower increase in V̇e and a lower hypoxic hypometabolism. In a second group of Nx and Hx hatchlings, the V̇e response to 10% O2was tested in the same hatchlings at the early and late hours. The results confirmed the lower hypoxic chemosensitivity of Hx. We conclude that hypoxic incubation affected the development of respiratory control, resulting in a blunted ventilatory chemosensitivity.
MKK3-p38 signaling promotes apoptosis and the early inflammatory response in the obstructed mouse kidney
Authors: Ma Frank Y. , Tesch Greg H. , Flavell Richard A. , Davis Roger J. , Nikolic-Paterson David J.
Published: August 2007

Activation of the p38 mitogen-activated protein kinase (MAPK) pathway induces inflammation, apoptosis, and fibrosis. However, little is known of the contribution of the upstream kinases, MMK3 and MKK6, to activation of the p38 kinase in the kidney and consequent renal injury. This study investigated the contribution of MKK3 to p38 MAPK activation and renal injury in the obstructed kidney. Groups of eight wild-type (WT) or Mkk3−/− mice underwent unilateral ureteric obstruction (UUO) and were killed 3 or 7 days later. Western blotting showed a marked increase in phospho-p38 (p-p38) MAPK in UUO WT kidney. The same trend of increased p-p38 MAPK was seen in the UUO Mkk3−/− kidney, although the actual level of p-p38 MAPK was significantly reduced compared with WT, and this could not be entirely compensated for by the increase in MKK6 expression in the Mkk3−/− kidney. Apoptosis of tubular and interstitial cells in WT UUO mice was reduced by 50% in Mkk3−/− UUO mice. Furthermore, cultured Mkk3−/− tubular epithelial cells showed resistance to H2O2-induced apoptosis, suggesting a direct role for MKK3-p38 signaling in tubular apoptosis. Upregulation of MCP-1 mRNA levels and macrophage infiltration seen on day 3 in WT UUO mice was significantly reduced in Mkk3−/− mice, but this difference was not evident by day 7. The development of renal fibrosis in Mkk3−/− UUO mice was not different from that seen in WT UUO mice. In conclusion, these studies identify discrete roles for MKK3-p38 signaling in renal cell apoptosis and the early inflammatory response in the obstructed kidney.
Stereological estimates indicate that aging does not alter the capillary length density in the human posterior cricoarytenoid muscle
Authors: Lyon Michael J. , Steer Linda M. , Malmgren Leslie T.
Published: August 2007

Studies of some human skeletal muscles demonstrate an age-related capillarity decrease. An age-related decrease in blood flow to the posterior cricoarytenoid muscle (PCA) in rats has been reported, as well as a decreased ability to abduct the vocal folds. We, therefore, hypothesized that decreased muscle capillarity may contribute to PCA dysfunction in the elderly. Using immunological and stereological techniques, human PCAs (ages 18–98 yr; 28 men, 23 women) were examined for age-related changes in muscle fiber-type-specific and/or total capillary length density. While analysis shows no age-related changes in total muscle or fiber-type-specific capillary length densities ( LV cap), there are significant age-related increases in LV cap within the interstitial tissue ( P = 0.001) and in the ratio of the type I LV cap to type I surface ( P = 0.002), with a strong trend for type II LV cap ( P = 0.055). There is also an age-related decrease in the muscle fiber surface density for both type I and II fibers ( P < 0.001 and 0.04, respectively). Data also show that women have a significantly higher type II LV cap ( P = 0.039), regardless of age. In addition, with the exception of female type I LV cap, all measured variables are significantly higher for type I fibers ( P < 0.001), independent of age or sex. While data indicate there are age-related changes of capillary-muscle fiber relationships within the PCA, they do not support the hypothesis of an age-related loss of capillarity.
Changes in sleep quality of athletes under normobaric hypoxia equivalent to 2,000-m altitude: a polysomnographic study
Authors: Hoshikawa Masako , Uchida Sunao , Sugo Takayuki , Kumai Yasuko , Hanai Yoshiteru , Kawahara Takashi
Published: August 2007

This study evaluated the sleep quality of athletes in normobaric hypoxia at a simulated altitude of 2,000 m. Eight male athletes slept in normoxic condition (NC) and hypoxic conditions equivalent to those at 2,000-m altitude (HC). Polysomnographic recordings of sleep included the electroencephalogram (EEG), electrooculogram, chin surface electromyogram, and electrocardiogram. Thoracic and abdominal motion, nasal and oral airflow, and arterial blood oxygen saturation (SaO2) were also recorded. Standard visual sleep stage scoring and fast Fourier transformation analyses of the EEG were performed on 30-s epochs. Subjective sleepiness and urinary catecholamines were also monitored. Mean SaO2 decreased and respiratory disturbances increased with HC. The increase in respiratory disturbances was significant, but the increase was small and subclinical. The duration of slow-wave sleep (stage 3 and 4) and total delta power (<3 Hz) of the all-night non-rapid eye movement sleep EEG decreased for HC compared with NC. Subjective sleepiness and amounts of urinary catecholamines did not differ between the conditions. These results indicate that acute exposure to normobaric hypoxia equivalent to that at 2,000-m altitude decreased slow-wave sleep in athletes, but it did not change subjective sleepiness or amounts of urinary catecholamines.
Laterality of Movement-Related Activity Reflects Transformation of Coordinates in Ventral Premotor Cortex and Primary Motor Cortex of Monkeys
Authors: Kurata Kiyoshi
Published: August 2007

The ventral premotor cortex (PMv) and the primary motor cortex (MI) of monkeys participate in various sensorimotor integrations, such as the transformation of coordinates from visual to motor space, because the areas contain movement-related neuronal activity reflecting either visual or motor space. In addition to relationship to visual and motor space, laterality of the activity could indicate stages in the visuomotor transformation. Thus we examined laterality and relationship to visual and motor space of movement-related neuronal activity in the PMv and MI of monkeys performing a fast-reaching task with the left or right arm, toward targets with visual and motor coordinates that had been dissociated by shift prisms. We determined laterality of each activity quantitatively and classified it into four types: activity that consistently depended on target locations in either head-centered visual coordinates (V-type) or motor coordinates (M-type) and those that had either differential or nondifferential activity for both coordinates (B- and N-types). A majority of M-type neurons in the areas had preferences for reaching movements with the arm contralateral to the hemisphere where neuronal activity was recorded. In contrast, most of the V-type neurons were recorded in the PMv and exhibited less laterality than the M-type. The B- and N-types were recorded in the PMv and MI and exhibited intermediate properties between the V- and M-types when laterality and correlations to visual and motor space of them were jointly examined. These results suggest that the cortical motor areas contribute to the transformation of coordinates to generate final motor commands.
Scintigraphy with 99mTc-labeled heat-altered erythrocytes in diagnosing hyposplenia
Authors: Bröker S. , Schlieck A. , Bauhofer A. , Herbst B. , Béhé M. , Corstens F. H. , Behr T. M. , Görg C. , Gotthardt M.
Published: August 2007

Aim: Ultrasound may be a cheap alternative to scintigraphic determination of splenic function. We directly compared nanocolloid scintigraphy (NS), scintigraphy with heat-altered erythrocytes (ES), and colour-coded Doppler sonography (DS) in patients with chronic inflammatory bowel disease (CIBD). Patients, methods: 35 patients were included into the study. Clearance rates were determined in ES, spleen/liver ratios (SLR) were measured scintigraphically in ES/NS. In DS, spleen size, echogenicity, and vascular resistance indices (RI) were determined. The results were compared to each other, to the clinical activity scores for CIBD, and to the course of the disease. Results: Based on the blood erythrocyte clearance serving as standard, patients had a good (19 patients), impaired (5), or missing splenic function (11). There was a good correlation of the clearance to SLR in ES (0.63, p <0.01). The 10 min / 45 min ES clearance showed a high correlation (Spearman- Rho 0.87, p <0.01). The SLR in ES at 2, 5, 10 and 45 min also correlated well with each other (Spearman- Rho >0.9, p <0.01; SLR >3.45 normal splenic function, SLR <1.22 indicated hyposplenia). There were no correlations between the results of NS, DS, Howell-Jollybodies, or clinical parameters. Only ES and the erythrocyte clearance correlated well. Howell-Jolly-Bodies detected 1 of 11 patients with hyposplenia while false-positive in 4. Conclusion: Ultrasound and colloid scintigraphy show a low correlation with clearance of heat-altered erythrocytes. Only ES shows a good correlation in patients with CIBD. The clearance at 10 min already reliably determines splenic function. SLR may be determined after 10 minutes and is predictive of normal function if above 3.45 while SLR <1.2 indicated hyposplenia.
Educators with Attitude: Insights from the Urban Church
Authors: Richardson Jenny
Published: August 2007

This article offers insights from an educational perspective for those enabling theology beyond the walls of the church. While the research has been carried out in an urban context, the principles identified have resonance for those grappling with the re-expression of church within a variety of changing UK cultures.
Reducing Material Costs with Microcellular/Fine-celled Foaming
Authors: Lee John W.S. , Park Chul B. , Kim Seong G.
Published: August 2007

Over the past few years, the steady increase in the cost of oil has resulted in higher resin prices. This market trend has imposed a significant burden on plastic parts manufacturers since resin typically accounts for 50—60% of the total manufacturing cost of plastics. In turn, many companies have been looking for ways to reduce the amount of resin they employ in order to compensate for their losses. In this study, high-density foaming experiments using polyethylene (HDPE) and polypropylene (PP) are carried out, demonstrating the extent to which these foaming processes represent breakthrough alternatives for plastics producers. N2 and talc are used as a blowing agent and as a nucleating agent, respectively. Two different pressure-drop rates are applied to study the effects of pressure-drop rates on HDPE and PP foams. It has been found that the cell density is the governing factor that determines the void fraction: the higher the cell density, the higher the void fraction. The authors successfully produced plastic foams that exhibited void fractions of up to 50% for HDPE and 40% for PP; these void fractions accounted for 40—50% reduction in material cost.
Expansion of Polystyrene Using Water as the Blowing Agent
Authors: Pallay J. , Pallayova S. , Berghmans H.
Published: August 2007

The expansion of polystyrene using water as the blowing agent has been investigated. Hydrophilic particles are dispersed in styrene before the suspension polymerization. During this polymerization the necessary amount of water is absorbed and/or adsorbed by these additives. The different additives used in this work are ordinary corn starch and high-amylose starch, zeolite A and Y, and SiO2. Factors that influence the density and the morphology of the expanded product are the type of additive, the additive and water content, the polymerization conditions, and the expansion procedure. High frequency electric field heating and hot air have been used for the expansion. The lowest density is obtained with high frequency electric field heating.
Art and Mental Disturbance
Authors: Benjamin Elliot
Published: August 2007

This article presents a psychological study of the “successful creative artist” and the relationship between art and mental disturbance. To elaborate, this article emphasizes what the author considers to be “natural” (i.e., self-motivated) creative self-expression in comparison to “normal” (i.e., socially approved) patterns of behavior. Although what is natural may overlap with what is considered normal in society, rarely are the two placed on equal footing. To illustrate this problem, the author introduces a new theory, “the artistic theory of psychology,” that casts a new light on the “successful” creative artist. Along the lines of Thomas Szasz and R. D. Laing, that which is referred to as “mental illness” is viewed from a nonjudgmental perspective but with the distinctive feature of suggesting that some people who are considered to be mentally ill may have significant creative artistic potential that can be highly therapeutic, both for them and for society at large.
Under What Conditions Do Public Managers Favor and Pursue Organizational Change?
Authors: Fernandez Sergio , Pitts David W.
Published: August 2007

Managerial leaders play a prominent role in organizational change--as champions for change and as key players in its implementation. This study seeks to understand why public managers choose to support change and initiate it within their organizations. A model of change-related attitude and behavior is developed and tested in the study. The results indicate that a complex pattern of internal and external factors influence a public manager's attitude and behavior relating to change. The results also suggest that top-down and bottom-up drivers of change work simultaneously to influence a public manager's decision to assume the role of a change agent.
Nonprofit Performance, Fund-Raising Effectiveness, and Strategies for Engaging African Americans in Philanthropy
Authors: Van Slyke David M. , Ashley Shena , Johnson Janet L.
Published: August 2007

During the past two decades, the field of philanthropy has grown in its knowledge base, knowledge sharing, and sophistication in reaching out to and cultivating donors and volunteers. The growing literature focusing on African American philanthropy has contributed to that knowledge base. Throughout much of the research conducted, African Americans are found to be an untapped philanthropic resource who have yet to be leveraged. Yet previous studies provide mixed results on giving and volunteering profiles and the impact of certain solicitation strategies. In this study, the authors use survey data from the Atlanta metro region to do what no other study on African American philanthropy has done. Using multivariate analysis, the authors match fundraising strategies to sociodemographic characteristics to create a development taxonomy to assist nonprofits in effectively engaging this group of potential donors. Nonprofit organizations can use these development taxonomies and empirical findings to enhance their fund-raising operations and improve nonprofit performance.
Citizen Attitudes Toward Transparency in Local Government
Authors: Piotrowski Suzanne J. , Van Ryzin Gregg G.
Published: August 2007

The proper balance between governmental secrecy and open government is at the forefront of contemporary public debate. Citizens have different degrees of interest in and demand for governmental transparency. Using data from a national online survey of more than 1,800 respondents, we develop several indices to measure citizens' demand for transparency at the local level and explore its correlates. We also examine the correlates of citizens' reported requests for information from local government. The data and analysis suggest that there are several dimensions to the public's demand for transparency, including fiscal, safety, and government concerns, and principled openness. Age, political ideology, confidence in government leaders, frequency of contacting government, and especially the perception that there is currently not enough access to government appear to drive the public's demand for transparency, although determinants differ for each dimension. Some, although not all, of these factors also predict citizens' actual requests for government information.