bluuebunny/crossref_metadata_2025 huggingface dataset:
Spectral imaging of proton aurora and twilight at Tromsø, Norway
Authors: Galand M. , Baumgardner J. , Pallamraju D. , Chakrabarti S. , Løvhaug U. P. , Lummerzheim D. , Lanchester B. S. , Rees M. H.
Published: July 2004

An imaging Echelle spectrograph designed for high‐resolution studies of selected spectral features located in the visible spectrum was deployed from November 2001 until April 2003 in Tromsø, Norway. For moderately disturbed magnetic conditions, Tromsø is located on the equatorial edge of the evening auroral oval for several hours. Energetic protons are frequently the dominant particle energy source in this region. For this experiment, four spectral windows were selected, each around different emission features: Hα (656.3 nm), Hβ (486.1 nm), N2+1NG 427.8 nm, and OI 777.4 nm. The 8° long slit of the spectrograph was centered on the magnetic zenith. This instrument provided simultaneous, high‐resolution (∼0.1 nm) spectra of Hα and Hβ emissions, which offers a unique opportunity to investigate the Hα to Hβ Balmer decrement in proton aurora. Information on the cloud cover and on the overall auroral activity was provided by a large field of view (70°) conventional imaging spectrograph that spans the 350–800 nm spectral range. In this paper we describe both instruments and demonstrate their capabilities for the study of the H Balmer emissions in twilight and during auroral activity. Our high‐resolution spectra taken in twilight could be used to observe the variability of the geocoronal component over time and to compare the derived variability with midlatitude sites. We conclude that the 0.1 nm spectral resolution is sufficient to identify and take into account contaminating OH and N2 1PG features in Hα emission profiles. Comparison of Hβ Doppler profiles observed at different locations (Tromsø, Poker Flat, Svalbard) in proton aurora is presented. Lummerzheim and Galand [2001] find that the shape of the violet wing of the Balmer profile is a more suitable indicator of the mean energy of the incident protons than the Doppler shift of the peak. Numerous uncertainties in measured and modeled Hα and Hβ line profiles preclude using the Balmer decrement as an indicator of the precipitating proton flux.
210Po and 210Pb distributions and residence times in the nearshore region of Lake Superior
Authors: Chai Yingtao , Urban Noel R.
Published: July 2004

The naturally occurring radionuclide, 210Pb, and its decay daughter, 210Po, were measured in the Keweenaw Peninsula region of Lake Superior. Water, suspended particles, sediment trap material (settling particles), and sediment cores and grab samples were collected along three transects that stretched from 1 to 20 km from shore. Departures from secular equilibrium (activity ratio of 210Po:210Pb = 1) were observed for most samples. 210Po‐deficiency was observed in both suspended particles (TSP) with a ratio of 0.43 ± 0.05 (±95% confidence interval (CI)) and settling particles with a ratio of 0.57 ± 0.04; higher ratios in the settling particles resulted from an admixture of resuspended sediments. Ratios in the dissolved phase were 0.45 ± 0.12. Approximately 83% and 85% of total 210Po and 210Pb in the water column was in the particulate phase. No evidence of biological uptake of Po was found. Seasonal and spatial variability in activities and ratios was small. Using steady state solutions to the mass balance equations for both isotopes, similar residence times in the water column were calculated for 210Po and 210Pb (55 ∼ 75 days in a 150‐m‐deep water column). It was possible to calibrate a one‐box model for the paired isotopes so that the model output closely matched rates of sediment and isotope resuspension estimated from sediment traps. However, this calibration required a fractionation of the isotopes during resuspension. The particle settling velocity was estimated to be 2.3 m d−1, which also is in agreement with the estimate (2.4 ± 2.2 m d−1) from sediment traps. These results indicate rapid fluxes of radioisotopes and sediments through the water column largely driven by resuspension of sediments in nearshore areas.
Aerial measurement of air pollutants and aerosols during 20–22 March 2001 over the East China Sea
Authors: Hatakeyama Shiro , Takami Akinori , Sakamaki Fumio , Mukai Hitoshi , Sugimoto Nobuo , Shimizu Atsushi , Bandow Hiroshi
Published: July 2004

Aerial measurement of atmospheric pollutants was carried out over the East China Sea on 20, 21, and 22 March 2001. High concentrations of not only gaseous species (maximum concentrations of SO2 > 10 ppb and O3 > 100 ppb in the marine boundary layer) but also particulate matter (PM) (average concentration of PM2.5 ∼ 30 μg m−3 and PM10 ∼ 1000 μg m−3 in the marine boundary layer) were observed on 21March. Such high concentrations were observed only at low altitude. A cold front passing over the Korean Peninsula and extension of a high‐pressure system from central China to the East China Sea were responsible for the transport of pollutants. High concentrations of pollutants were confined to lower altitude by the high‐pressure system. This result is in marked contrast to our previous observation: A highly polluted air mass was transported from central China when a low‐pressure system originating near Taiwan moved northeast to Japan along the south coast of the main islands. Anthropogenic sulfate aerosols were transported ahead of Kosa particles (fine yellow sand dust particles). A humid air mass containing a high concentration of sulfate (>20 μg m−3) was followed by a dry air mass containing a high concentration of calcium (>1000 μg m−3). Interactions between aerosol components and anthropogenic gaseous species gave insight into the formation process of aerosols over the East China Sea. Nitrate showed a good correlation with calcium except in the highly polluted air mass, indicating that gaseous nitric acid was adsorbed on the surface of coarse particles. No correlation between nitrate and ammonium supported this contention. In contrast, sulfate showed an excellent linear correlation with ammonium, indicating quick neutralization of sulfuric acid by ammonia in the polluted air mass. Exceptions were observed when the calcium concentration was >4 μg m−3, suggesting that SO2 gas was adsorbed on the surface of yellow sand dust particles and that oxidation took place on the surface.
Trends in pan evaporation and actual evapotranspiration across the conterminous U.S.: Paradoxical or complementary?
Authors: Hobbins Michael T. , Ramírez Jorge A. , Brown Thomas C.
Published: July 2004

Pan evaporation (ETpan) has decreased at 64% of pans in the conterminous U.S. over the past half‐century. Comparing trends in ETpan and water budget‐derived actual evapotranspiration (ET*a), we observe the so‐called “Pan Evaporation Paradox,” which we confirm is no more than a manifestation of the complementarity between actual evapotranspiration (ETa) and potential evapotranspiration (ETp). Examining trends in the components of ETa—the radiative energy and regional advective budgets—we show that both components must be considered together to explain the relationship between ETpan and ET*a.
Permafrost thaw and destabilization of Alpine rock walls in the hot summer of 2003
Authors: Gruber Stephan , Hoelzle Martin , Haeberli Wilfried
Published: July 2004

Exceptional rockfall occurred throughout the Alps during the unusually hot summer of 2003. It is likely related to the fast thermal reaction of the subsurface of steep rock slopes and a corresponding destabilization of ice‐filled discontinuities. This suggests that rockfall may be a direct and unexpectedly fast impact of climate change. Based upon our measurements in Alpine rock faces, we present model simulations illustrating the distribution and degradation of permafrost where the summer of 2003 has resulted in extreme thaw. We argue that hotter summers predicted by climate models for the coming decades will result in reduced stability of many alpine rock walls.
Super‐large raindrops
Authors: Hobbs Peter V. , Rangno Arthur L.
Published: July 2004

Raindrops similar or greater in size to the largest ever observed, with maximum dimensions of at least 8.8 mm and possibly 1 cm, have been measured in rainshafts beneath cumulus congestus clouds spawned by a biomass fire in Brazil and in very clean conditions in the Marshall Islands. It is proposed that the super‐large raindrops were produced by the rapid growth of drops colliding with each other within narrow regions of cloud where liquid water contents were unusually high. In Brazil, the initial growth of super‐large raindrops might have been initiated by condensation onto giant smoke particles.
Three‐dimensional modeling of ozone on Mars
Authors: Lefèvre Franck , Lebonnois Sébastien , Montmessin Franck , Forget François
Published: July 2004

We present the first three‐dimensional model simulations of ozone on Mars. The model couples a state‐of‐the‐art gas‐phase photochemical package to the general circulation model developed at Laboratoire de Météorologie Dynamique (LMD). The results do not contradict the classical picture of a global anticorrelation between the ozone (O3) and water vapor columns. However, the quantitative approach shows significant departures from this relationship, related to substantial orbital variations in the O3 vertical distribution. Over the period Ls = 180°–330°, low‐latitude to midlatitude O3 is essentially confined below 20 km, has a weak diurnal cycle, and is largely modulated by topography. During the rest of the year (Ls = 330°–180°) the model predicts the formation of an O3 layer at 25–70 km altitude, characterized by nighttime densities about one order of magnitude larger than during the day. Throughout the year, high‐latitude O3 peaks near the surface and reaches maximum integrated amounts (∼40 μm‐atm) in the winter polar vortex, with considerable (30 to 50%) dynamically induced day‐to‐day variations. The most stringent comparison to date with O3 observational data reveals contrasted results. A good quantitative agreement is found in the postperihelion period (Ls = 290°–10°), but the model fails to reproduce O3 columns as large as those measured near aphelion (Ls = 61°–67°). Current uncertainties in absorption cross sections and gas‐phase kinetics data do not seem to provide credible explanations to explain this discrepancy, which may suggest the existence of heterogeneous processes.
Relationship Between Heart Rate Turbulence and Heart Rate, Heart Rate Variability, and Number of Ventricular Premature Beats in Coronary Patients
Authors: CYGANKIEWICZ IWONA , WRANICZ JERZY KRZYSZTOF , BOLINSKA HALINA , ZASLONKA JANUSZ , ZAREBA WOJCIECH
Published: July 2004

Introduction: Heart rate variability (HRV) illustrates regulation of the heart by the autonomic nervous system whereas heart rate turbulence (HRT) is believed to reflect baroreflex sensitivity. The aim of this study was to determine the association between HRT and HRV parameters and the relationship between HRT parameters and heart rate and number of ventricular premature beats (VPBs) used to calculate HRT parameters.

Methods and Results: In 146 patients (117 males and 29 females; mean age 62 years) with coronary artery disease, a 24‐hour ECG Holter monitoring was performed to calculate mean heart rate (RR interval), number of VPBs, time‐ and frequency‐domain HRV parameters and two HRT parameters: turbulence onset (TO) and turbulence slope (TS). Univariate and multivariate regression analyses were performed to evaluate the association between tested parameters. Significant correlation between TS and mean RR interval was observed (r = 0.42; p < 0.001), while no association for TO vs. RR interval was found. TS values were significantly higher in patients with less than 10 VPBs/24 hours than in patients with more frequent VPBs. Significant associations between HRT and HRV parameters were found with TS showing stronger correlation with HRV parameters than TO (r value ranging from 0.35 to 0.62 for TS vs. −0.16 to −0.38 for TO).

Conclusion: HRT parameters correlate strongly with HRV parameters indicating that HRT should be considered as a reflection of both baroreceptors response and overall autonomic tone. Heart rate dependence of turbulence slope indicates the need to adjust this parameter for heart rate. (J Cardiovasc Electrophysiol, Vol. 15, pp. 731‐737, July 2004)
Automaticity in Mahaim Fibers
Authors: STERNICK EDUARDO BACK , SOSA EDUARDO A. , TIMMERMANS CARL , FILHO FERNANDO E. CRUZ , RODRIGUEZ LUZ‐MARIA , GERKEN LUIZ M. , SCANAVACCA MAURÍCIO I. , FAGUNDES MÁRCIO L. , BUENO SÁVIA C. , VRANDECIC MÁRIO O. , WELLENS HEIN J.J.
Published: July 2004

Introduction: Automatic rhythms associated with Mahaim fibers usually occur during radiofrequency catheter ablation. The incidence and significance of spontaneous automaticity in Mahaim fibers are unknown.

Methods and Results: Spontaneous automatic rhythms were observed in 5 (12.5%) of 40 patients with Mahaim fibers referred for nonpharmacologic therapy because of recurrent episodes of symptomatic tachyarrhythmias, usually antidromic circus movement tachycardia (33/40 patients). Three were female and two were male. Their mean age was 15 ± 7 years compared to 26 ± 13 years of the patients without automaticity (P = 0.09). Three patients had both antidromic tachycardia and asymptomatic spontaneous automatic rhythms recorded during ambulatory ECG (1 patient) or electrophysiologic study (2 patients). In 2 patients, the automatic rhythm triggered antidromic tachycardia. Two other patients had nonsustained repetitive episodes of wide QRS tachycardia due to automaticity arising in the Mahaim fiber, without antidromic tachycardia. All automatic rhythms were abolished by successful catheter ablation of the Mahaim fibers.

Conclusion: Spontaneous automaticity occurred in 12.5% of our Mahaim patients and may trigger antidromic tachycardia. Spontaneous automaticity, which is not seen in rapidly conducting accessory pathways, is another argument for the presence of an AV nodal‐like structure in Mahaim fibers. (J Cardiovasc Electrophysiol, Vol. 15, pp. 738‐744, July 2004)
Optimization of Atrial Defibrillation with a Dual‐Coil, Active Pectoral Lead System
Authors: RASHBA ERIC J. , SHOROFSKY STEPHEN R. , PETERS ROBERT W. , GOLD MICHAEL R.
Published: July 2004

Introduction: Atrial defibrillation can be achieved with standard implantable cardioverter defibrillator (ICD) leads, but the optimal shocking configuration is unknown. The objective of this prospective study was to compare atrial defibrillation thresholds (DFTs) with three shocking configurations that are available with standard ICD leads.

Methods and Results: This study was a prospective, randomized, paired comparison of shocking configurations on atrial DFTs in 58 patients. The lead system evaluated was a transvenous defibrillation lead with coils in the superior vena cava (SVC) and right ventricular apex (RV) and a left pectoral pulse generator emulator (Can). In the first 33 patients, atrial DFT was measured with the ventricular triad (RV → SVC + Can) and unipolar (RV → Can) shocking pathways. In the next 25 patients, atrial DFT was measured with the ventricular triad and the proximal triad (SVC → RV + Can) configurations. Delivered energy at DFT was significantly lower with the ventricular triad compared to the unipolar configuration (4.7 ± 3.7 J vs 10.1 ± 9.5 J, P < 0.001). Peak voltage and shock impedance also were significantly reduced (P < 0.001). There was no significant difference in DFT energy when the ventricular triad and proximal triad shocking configurations were compared (3.6 ± 3.0 J vs 3.4 ± 2.9 J for ventricular and proximal triad, respectively, P = NS). Although shock impedance was reduced by 13% with the proximal triad (P < 0.001), this effect was offset by an increased current requirement (10%).

Conclusion: The ventricular triad is equivalent or superior to other possible shocking pathways for atrial defibrillation afforded by a dual‐coil, active pectoral lead system. Because the ventricular triad is also the most efficacious shocking pathway for ventricular defibrillation, this pathway should be preferred for combined atrial and ventricular defibrillators. (J Cardiovasc Electrophysiol, Vol. 15, pp. 790‐794, July 2004)
The Cell Wall‐Modifying Xyloglucan Endotransglycosylase/Hydrolase LeXTH1 is Expressed during the Defence Reaction of Tomato against the Plant Parasite Cuscuta reflexa
Authors: Albert M. , Werner M. , Proksch P. , Fry S. C. , Kaldenhoff R.
Published: July 2004

Abstract: A suppressive subtractive hybridization technique was used to identify genes, which were induced during the early phases of the interaction between dodder (Cuscuta reflexa), a phanerogamic parasite, and its incompatible host plant tomato. One of the identified genes encodes a tomato xyloglucan endotransglycosylase/hydrolase (XTH) ‐ an enzyme involved in cell wall elongation and restructuring. The corresponding LeXTH1 mRNA accumulated 6 h after attachment of the parasite. In contrast, wounding did not influence the expression level. Subsequent to LeXTH1 mRNA accumulation, an increase in XTH activity at the infection sites as well as in adjacent tissues was observed. The effect of IAA on LeXTH1 expression was analyzed because the concentration of this phytohormone is known to increase in the tomato tissue during the interaction with the parasite. LeXTH1 mRNA accumulation was in fact induced by external application of auxin. However, in the auxin‐insensitive tomato mutant diageotropica, Cuscuta induced LeXTH1‐mRNA accumulated with a time course similar to wild type tomato. Thus, auxin appears not to be an essential signal for infection‐induced LeXTH1 activation. Our data suggest a role for xyloglucan transglycosylation in defence reactions associated with the incompatible tomato‐Cuscuta interaction.
Aquaporin Functionality in Roots of Zea mays in Relation to the Interactive Effects of Boron and Salinity
Authors: Bastías E. , Fernández‐García N. , Carvajal M.
Published: July 2004

Abstract: Zea mays L. cv. amylacea, a plant tolerant of B and salinity, was used to determine the involvement of aquaporin functionality in the interactive effects of B and salinity. Also, growth, chlorophyll concentration, and water relations were studied. While growth and chlorophyll concentration did not show noticeable changes under saline conditions, the decrease in leaf water potential and osmotic potential, together with the marked decrease of stomatal conductance and root hydraulic conductance, showed that the plants were adjusted osmotically. However, no effect of B was observed. The very weak response of the Lpc of salt‐stressed roots to Hg suggested that water channels were greatly reduced in number or, if present, were non‐functional. The evidence that substantial B movement can occur through diffusion and channel‐mediated transport is compelling, and could account for B uptake under conditions of adequate or greater B supply. Therefore, the reduction in the functionality of aquaporins for NaCl‐treated plants could be related to the reduction of B concentrations in roots and leaves in B + NaCl‐treated plants, in comparison with plants treated only with B.
The Distribution and Phylogeny of Aluminium Accumulating Plants in the Ericales
Authors: Jansen S. , Watanabe T. , Caris P. , Geuten K. , Lens F. , Pyck N. , Smets E.
Published: July 2004

Abstract: The distribution of aluminium (Al) accumulation in the Ericales is surveyed, based on semi‐quantitative tests of 114 species and literature data. Al accumulation mainly characterises the families Diapensiaceae, Pentaphylacaceae, Symplocaceae, Ternstroemiaceae, and Theaceae. Al accumulation is consistently present or absent in most families examined, but the character appears to be more variable in a few taxa (e.g., Lecythidaceae, Myrsinaceae). Although the interfamilial relationships within the Ericales require further research, the ability to accumulate high levels of Al appears to show considerable taxonomic significance. While the majority of Al accumulating Ericales includes woody, tropical plants, the feature is remarkably present in several herbaceous Diapensiaceae, which have a distribution in cold to temperate areas. The association of different mycorrhizae types with plant roots is suggested to play a role in the exclusion of high Al levels from the shoot.
Two‐Dimensional Tension Tests in Plant Biomechanics ‐ Sweet Cherry Fruit Skin as a Model System
Authors: Bargel H. , Spatz H.‐C. , Speck T. , Neinhuis C.
Published: July 2004

Abstract:Splitting of fruits is a function of two‐dimensional tension caused by different growth rates of tissues and turgor, especially water uptake shortly before harvest. In order to analyse the mechanical properties of spheroid plant material close to stress‐strain conditionsin vivo,a new hydraulic two‐dimensional testing device was set up. Sweet cherry (Prunus aviumL.) fruit skin was chosen as a model system. The recorded pressure‐deflection curves were non‐linear, with a considerable initial “lag phase” and a distinct increasing end part. Taking into account the special geometry, these curves could be modelled with a newly developed analytical approach based on linear elastic material behaviour. The results demonstrated good correlation if a modulus of elasticity ranging from 160 to 250 MPa for the cherry fruit skin was chosen. In addition, a mean strength value of 47 MPa was calculated based on the theory of thin shells and spheres. The results are compared with mechanical data found for fruits and other plant material. In order to test the theoretical approach, two‐ and one‐dimensional tension tests were performed on packaging PE foil, revealing a mean modulus of 171 MPa in bi‐axial tension, and 193 and 242 MPa in uni‐axial tension, depending on the test speed. The results demonstrate that it seems to be feasible to use this method to analyse the two‐dimensional stress‐strain conditions of spheroid plant materials such as cherry fruit skins. It may be applied as a tool for crop testing to elucidate the mechanical basis of cracking susceptibility of fruits.
Raise your Glasses - the Water's Magic! Strategic IT at SA Water: A Case Study in Alignment, Outsourcing and Governance
Authors: Thorogood Alan , Yetton Philip , Vlasic Anthony , Spiller Joan
Published: July 2004

The South Australian Water case study illustrates the management challenges in aligning Information Technology with business objectives in a publicly owned corporation. To achieve the alignment, the new CIO begins by refreshing the IT infrastructure to support the required business applications. When the Government establishes ‘Improved water quality’ as a major corporate goal, the CIO seeks to add value to the business by developing a quality reporting system that leverages the existing technology. At the same time, he demonstrates to the corporation the IT function's capability to deliver business value through the management of multiple outsourcing vendors.
Making Organisations Virtual: The Hidden Cost of Distributed Teams
Authors: Breu Karin , Hemingway Christopher J
Published: July 2004

This paper reports an exploratory case study that used boundary theory to investigate the impact of organisational virtualisation on work units. Specifically, the research analysed the transition in a public sector organisation from permanent, co-located teams to temporary virtual teams and its impact on team boundary properties and activities. The study contributes to existing knowledge of virtual teams and virtualisation processes in several ways. The findings suggest that, contrary to existing thinking, rather than removing organisational and institutional boundaries, virtualisation increases the number and complexity of such boundaries at the work unit level. The findings also indicate that the chronic lack of knowledge sharing on virtual teams is, in addition to difficulties of establishing interpersonal trust, due to a lack of trust in the technology as an appropriate medium for sensitive knowledge sharing. The implications of the study for practice are that efficiency gains from organisational virtualisation can easily be offset by the need to invest additional resources and team members’ time into cultivating a greater number of transient relationships at a distance. Organisations also need to invest in opportunities for face-to-face interaction where sensitive knowledge sharing is a critical resource for a virtual team.
REN
KCTD11
is a suppressor of Hedgehog signaling and is deleted in human medulloblastoma
Authors: Di Marcotullio Lucia , Ferretti Elisabetta , De Smaele Enrico , Argenti Beatrice , Mincione Claudia , Zazzeroni Francesca , Gallo Rita , Masuelli Laura , Napolitano Maddalena , Maroder Marella , Modesti Andrea , Giangaspero Felice , Screpanti Isabella , Alesse Edoardo , Gulino Alberto
Published: July 2004

Hedgehog signaling is suggested to be a major oncogenic pathway in medulloblastoma, which arises from aberrant development of cerebellar granule progenitors. Allelic loss of chromosome 17p has also been described as the most frequent genetic defect in this human neoplasia. This observation raises the question of a possible interplay between 17p deletion and the Hedgehog tumorigenic pathway. Here, we identify the human orthologue of mouse REN
KCTD11
, previously reported to be expressed in differentiating and low proliferating neuroblasts. Human REN
KCTD11
maps to 17p13.2 and displays allelic deletion as well as significantly reduced expression in medulloblastoma. REN
KCTD11
inhibits medulloblastoma cell proliferation and colony formation
in vitro
and suppresses xenograft tumor growth
in vivo
. REN
KCTD11
seems to inhibit medulloblastoma growth by negatively regulating the Hedgehog pathway because it antagonizes the Gli-mediated transactivation of Hedgehog target genes, by affecting Gli1 nuclear transfer, and its growth inhibitory activity is impaired by Gli1 inactivation. Therefore, we identify REN
KCTD11
as a suppressor of Hedgehog signaling and suggest that its inactivation might lead to a deregulation of the tumor-promoting Hedgehog pathway in medulloblastoma.
The mitochondrial genome of
Paraspadella gotoi
is highly reduced and reveals that chaetognaths are a sister group to protostomes
Authors: Helfenbein Kevin G. , Fourcade H. Matthew , Vanjani Rohit G. , Boore Jeffrey L.
Published: July 2004

We report the complete mtDNA sequence from a member of the phylum Chaetognatha (arrow worms). The
Paraspadella gotoi
mtDNA is highly unusual, missing 23 of the genes commonly found in animal mtDNAs, including
atp6
, which has otherwise been found universally to be present. Its 14 genes are unusually arranged into two groups, one on each strand. One group is punctuated by numerous noncoding intergenic nucleotides although the other group is tightly packed, having no noncoding nucleotides, leading to speculation that there are two transcription units with differing modes of expression. The phylogenetic position of the Chaetognatha within the Metazoa has long been uncertain, with conflicting or equivocal results from various morphological analyses and rRNA sequence comparisons. Comparisons here of amino acid sequences from mitochondrially encoded proteins give a single most parsimonious tree that supports a position of Chaetognatha as sister to the protostomes studied here. From this analysis, one can more clearly interpret the patterns of evolution of various developmental features, especially regarding the embryological fate of the blastopore.
Binding of platelet glycoprotein Ibα to von Willebrand factor domain A1 stimulates the cleavage of the adjacent domain A2 by ADAMTS13
Authors: Nishio Kenji , Anderson Patricia J. , Zheng X. Long , Sadler J. Evan
Published: July 2004

von Willebrand factor (vWF) is a multimeric plasma glycoprotein with three tandem A domains. Domains A1 and A3 bind to platelet glycoprotein Ibα (GPIbα) and collagen, respectively. Domain A2 contains the Tyr-1605–Met-1606 bond that is cleaved by the metalloprotease ADAMTS13, and this reaction inhibits platelet thrombus growth. Fluid shear stress increases the rate of cleavage, suggesting that productive interaction with ADAMTS13 requires conformational changes within or near domain A2. The influence of the adjacent A1 and A3 domains was assessed by mutagenesis of a recombinant substrate consisting of domains A1A2A3. Deletion of domain A3 did not affect cleavage by ADAMTS13, whereas deletion of domain A1 increased the rate of cleavage ≈10-fold. Similar effects were observed with plasma ADAMTS13 and recombinant ADAMTS13 truncated after the spacer domain. Digestion of A1A2A3 by plasma ADAMTS13 was enhanced to a similar extent by a recombinant mutant fragment of platelet GPIbα that binds with high affinity to domain A1 or by heparin. Heparin also increased the digestion of purified plasma vWF. Neither GPIbα nor heparin increased the cleavage of substrate A2A3 that lacks domain A1. The results suggest that vWF domain A1 inhibits the cleavage of domain A2, and that inhibition can be relieved by interaction of domain A1 with platelet GPIbα or certain glycosaminoglycans. Thus, binding of vWF to its major physiological ligands may promote the feedback inhibition of platelet adhesion by stimulating the cleavage of domain A2 by ADAMTS13 independent of fluid shear stress.
The Treacher Collins syndrome (
TCOF1
) gene product is involved in ribosomal DNA gene transcription by interacting with upstream binding factor
Authors: Valdez Benigno C. , Henning Dale , So Rolando B. , Dixon Jill , Dixon Michael J.
Published: July 2004

Treacher Collins syndrome (TCS) is an autosomal dominant disorder characterized by an abnormality of craniofacial development that arises during early embryogenesis. TCS is caused by mutations in the gene
TCOF1
, which encodes the nucleolar phosphoprotein treacle. Even though the genetic alterations causing TCS have been uncovered, the mechanism underlying its pathogenesis and the function of treacle remain unknown. Here, we show that treacle is involved in ribosomal DNA gene transcription by interacting with upstream binding factor (UBF). Immunofluorescence labeling shows treacle and UBF colocalize to specific nucleolar organizer regions and cosegregate within nucleolar caps of actinomycin
d
-treated HeLa cells. Biochemical analysis shows the association of treacle and UBF with chromatin. Immunoprecipitation and the yeast two-hybrid system both suggest physical interaction of the two nucleolar phosphoproteins. Down-regulation of treacle expression using specific short interfering RNA results in inhibition of ribosomal DNA transcription and cell growth. A similar correlation is observed in
Tcof
+/-
mouse embryos that exhibit craniofacial defects and growth retardation. Thus, treacle haploinsufficiency in TCS patients might result in abnormal development caused by inadequate ribosomal RNA production in the prefusion neural folds during the early stages of embryogenesis. The elucidation of a physiological function of treacle provides important information of relevance to the molecular dissection of the biochemical pathology of TCS.
Trim5α protein restricts both HIV-1 and murine leukemia virus
Authors: Yap Melvyn W. , Nisole Sébastien , Lynch Clare , Stoye Jonathan P.
Published: July 2004

Replication of HIV-1 and N-tropic murine leukemia virus (N-MLV) is restricted in a number of different primate cells. In some cell lines, cross-saturation experiments suggest that the two viruses are interacting with the same restriction factor. Recently, Trim5α protein from rhesus monkey was found to restrict HIV-1. We have confirmed this result and have shown that Trim5α from two African green monkey cell lines, Vero and CV-1, also restricts HIV-1. In addition, we show that human, rhesus, and African green monkey Trim5α can restrict N-MLV. By using a panel of MLV capsid mutants, subtle differences in the anti-MLV activity were identified among the different primate Trim5α cDNAs. Trim1 isolated from humans and green monkeys was also found to restrict N-MLV. We hypothesize that the Trim family of proteins plays a widespread role in innate immunity to viral infection.
Lack of Toll-like receptor 4 or myeloid differentiation factor 88 reduces atherosclerosis and alters plaque phenotype in mice deficient in apolipoprotein E
Authors: Michelsen Kathrin S. , Wong Michelle H. , Shah Prediman K. , Zhang Wenxuan , Yano Juliana , Doherty Terence M. , Akira Shizuo , Rajavashisth Tripathi B. , Arditi Moshe
Published: July 2004

Toll-like receptors (TLRs) and the downstream adaptor molecule myeloid differentiation factor 88 (MyD88) play an essential role in the innate immune responses. Here, we demonstrate that genetic deficiency of TLR4 or MyD88 is associated with a significant reduction of aortic plaque areas in atherosclerosis-prone apolipoprotein E-deficient mice, despite persistent hypercholesterolemia, implying an important role for the innate immune system in atherogenesis. Apolipoprotein E-deficient mice that also lacked TLR4 or MyD88 demonstrated reduced aortic atherosclerosis that was associated with reductions in circulating levels of proinflammatory cytokines IL-12 or monocyte chemoattractant protein 1, plaque lipid content, numbers of macrophage, and cyclooxygenase 2 immunoreactivity in their plaques. Endothelial-leukocyte adhesion in response to minimally modified low-density lipoprotein was reduced in aortic endothelial cells derived from MyD88-deficient mice. Taken together, our results suggest an important role for TLR4 and MyD88 signaling in atherosclerosis in a hypercholesterolemic mouse model, providing a pathophysiologic link between innate immunity, inflammation, and atherogenesis.
Met provides essential signals for liver regeneration
Authors: Borowiak Malgorzata , Garratt Alistair N. , Wüstefeld Torsten , Strehle Michael , Trautwein Christian , Birchmeier Carmen
Published: July 2004

Genetic analysis in mice has demonstrated a crucial role of the Met tyrosine kinase receptor and its ligand, hepatocyte growth factor/scatter factor (HGF/SF), in development of the liver, muscle, and placenta. Here, we use conditional mutagenesis in mice to analyze the function ofMetduring liver regeneration, using theMx-cretransgene to introduce the mutation in the adult. After partial hepatectomy in mice carrying theMx-cre-inducedMetmutation, regeneration of the liver is impaired. Comparison of signal transduction pathways in control and mutant livers indicates that Met and other signaling receptors cooperate to fully activate particular signaling molecules, for instance, the protein kinase Akt. However, activation of the Erk1/2 kinase during liver regeneration depends exclusively on Met. Signaling crosstalk is thus an important aspect of the regulation of liver regeneration. Analysis of cell cycle progression of hepatocytes in conditionalMetmutant mice indicates a defective exit from quiescence and diminished entry into S phase. Impaired liver regeneration is accompanied by compensatory physiological responses that include prolonged up-regulation of HGF/SF and IL-6 in peripheral blood. Our data demonstrate that the HGF/SF/Met signaling system is essential not only during liver development but also for the regeneration of the organ in the adult.
An alternative agriculture system is defined by a distinct expression profile of select gene transcripts and proteins
Authors: Kumar Vinod , Mills Douglas J. , Anderson James D. , Mattoo Autar K.
Published: July 2004

Conventional agriculture has relied heavily on chemical inputs that have negatively impacted the environment and increased production costs. Transition to agricultural sustainability is a major challenge and requires that alternative agricultural practices are scientifically analyzed to provide a sufficiently informative knowledge base in favor of alternative farming practices. We show a molecular basis for delayed leaf senescence and tolerance to diseases in tomato plants cultivated in a legume (hairy vetch) mulch-based alternative agricultural system. In the hairy vetch-cultivated plants, expression of specific and select classes of genes is up-regulated compared to those grown on black polyethylene mulch. These include N-responsive genes such as
NiR
,
GS1
,
rbcL
,
rbcS
, and
G6PD
; chaperone genes such as
hsp70
and
BiP
; defense genes such as chitinase and osmotin; a cytokinin-responsive gene
CKR
; and gibberellic acid 20 oxidase. We present a model of how their protein products likely complement one another in a field scenario to effect efficient utilization and mobilization of C and N, promote defense against disease, and enhance longevity.
Selective disruption of PPARγ2 impairs the development of adipose tissue and insulin sensitivity
Authors: Zhang Jifeng , Fu Mingui , Cui Taixing , Xiong Chen , Xu Kefeng , Zhong Wei , Xiao Yan , Floyd Donna , Liang Jian , Li En , Song Qing , Chen Yuqing E.
Published: July 2004

Peroxisome proliferator-activated receptor γ (PPARγ) is a nuclear receptor that plays a pivotal role in obesity and diabetes. PPARγ has two isoforms, PPARγ1 and PPARγ2. We investigated the functional differences between PPARγ1 and PPARγ2 by selectively disrupting PPARγ2 in mice. In contrast to the embryonic lethality of PPARγ-deficient mice,
PPAR
γ
2

-
/
-

mice survived. Although normal development was identified in other tissues we examined,
PPAR
γ
2

-
/
-

mice exhibited an overall reduction in white adipose tissue, less lipid accumulation, and decreased expression of adipogenic genes in adipose tissue. In addition, insulin sensitivity was impaired in male
PPAR
γ
2

-
/
-

mice, with dramatically decreased expression of insulin receptor substrate 1 and glucose transporter 4 in the skeletal muscle, but thiazolidinediones were able to normalize this insulin resistance. Consistent with
in vivo
data,
PPAR
γ
2

-
/
-

mouse embryonic fibroblasts showed a dramatically reduced capacity for adipogenesis
in vitro
compared with wild-type mouse embryonic fibroblasts. Taken together, our data demonstrate that
PPAR
γ
2
deficiency impairs the development of adipose tissue and insulin sensitivity.
PPAR
γ
2

-
/
-

mice may provide a tool to study the role of PPARγ2 in obesity and diabetes.
Tree-structured supervised learning and the genetics of hypertension
Authors: Huang Jing , Lin Alfred , Narasimhan Balasubramanian , Quertermous Thomas , Hsiung C. Agnes , Ho Low-Tone , Grove John S. , Olivier Michael , Ranade Koustubh , Risch Neil J. , Olshen Richard A.
Published: July 2004

This paper is about an algorithm, FlexTree, for general supervised learning. It extends the binary tree-structured approach (Classification and Regression Trees, CART) although it differs greatly in its selection and combination of predictors. It is particularly applicable to assessing interactions: gene by gene and gene by environment as they bear on complex disease. One model for predisposition to complex disease involves many genes. Of them, most are pure noise; each of the values that is not the prevalent genotype for the minority of genes that contribute to the signal carries a “score.” Scores add. Individuals with scores above an unknown threshold are predisposed to the disease. For the additive score problem and simulated data, FlexTree has cross-validated risk better than many cutting-edge technologies to which it was compared when small fractions of candidate genes carry the signal. For the model where only a precise list of aberrant genotypes is predisposing, there is not a systematic pattern of absolute superiority; however, overall, FlexTree seems better than the other technologies. We tried the algorithm on data from 563 Chinese women, 206 hypotensive, 357 hypertensive, with information on ethnicity, menopausal status, insulin-resistant status, and 21 loci. FlexTree and Logic Regression appear better than the others in terms of Bayes risk. However, the differences are not significant in the usual statistical sense.
Primate jumping genes elucidate strepsirrhine phylogeny
Authors: Roos Christian , Schmitz Jürgen , Zischler Hans
Published: July 2004

Transposable elements provide a highly informative marker system for analyzing evolutionary histories. To solve controversially discussed topics in strepsirrhine phylogeny, we characterized 61 loci containing short interspersed elements (SINEs) and determined the SINE presence–absence pattern at orthologous loci in a representative strepsirrhine panel. This SINE monolocus study was complemented by a Southern blot analysis tracing multiple loci of two different strepsirrhine specific SINEs. The results thereof were combined with phylogenetic trees reconstructed on the basis of complete mitochondrial cytochromebsequences from all recognized strepsirrhine genera. Here we present evidence for (i) a sister group relationship of Malagasy Chiromyiformes and Lemuriformes, (ii) Lorisidae being a monophyletic sister clade to the Galagidae, and (iii) common ancestry of African and Asian lorisids. Based on these findings, we conclude that strepsirrhines originated in Africa and that Madagascar and Asia were colonized by respective single immigration events. In agreement with paleocontinental data, the molecular analyses suggest a crossing of the Mozambique channel by rafting between the late Cretaceous and the middle Eocene, whereas Asia was most likely colonized between the early Eocene and the middle Oligocene on a continental route. Furthermore, one SINE integration links the two Lemuriformes families, Lemuridae and Indriidae, indicating a common origin of diurnality or cathemerality and a later reversal to nocturnality by the indriid genusAvahi.
Requirement of matrix metalloproteinase-9 for the transformation of human mammary epithelial cells by Stat3-C
Authors: Dechow Tobias N. , Pedranzini Laura , Leitch Andrea , Leslie Kenneth , Gerald William L. , Linkov Irina , Bromberg Jacqueline F.
Published: July 2004

Persistently activated Stat3 is found in many different cancers, including ≈60% of breast tumors. Here, we demonstrate that a constitutively activated Stat3 transforms immortalized human mammary epithelial cells and that this oncogenic event requires the activity of matrix metalloproteinase-9 (MMP-9). By immunohistochemical analysis, we observe a positive correlation between strong MMP-9 expression and tyrosine phosphorylated Stat3 in primary breast cancer specimens. These results demonstrate a relationship between activated Stat3 and MMP-9 in breast oncogenesis.
Bipolar orientation of chromosomes in
Saccharomyces cerevisiae
is monitored by Mad1 and Mad2, but not by Mad3
Authors: Lee Marina S. , Spencer Forrest A.
Published: July 2004

The spindle checkpoint governs the timing of anaphase separation of sister chromatids. In budding yeast, Mad1, Mad2, and Mad3 proteins are equally required for arrest in the presence of damage induced by antimicrotubule drugs or catastrophic loss of spindle structure. We find that the
MAD
genes are not equally required for robust growth in the presence of more subtle kinetochore and microtubule damage. A
mad1
Δ synthetic lethal screen identified 16 genes whose deletion in cells lacking
MAD1
results in death or slow growth. Eleven of these
mad1
Δ genetic interaction partners encode proteins at the kinetochore–microtubule interface. Analysis of the entire panel revealed similar phenotypes in combination with
mad2
Δ. In contrast, 13 panel mutants exhibited a less severe phenotype in combination with
mad3
Δ. Checkpoint arrest in the absence of bipolar orientation and tension (induced by replication block in a cdc6 mutant) was lacking in cells without
MAD1
or
MAD2
. Cells without
MAD3
were checkpoint-proficient. We conclude that Mad1 and Mad2 are required to detect bipolar orientation and/or tension at kinetochores, whereas Mad3 is not.
A methionine aminopeptidase-2 inhibitor, PPI-2458, for the treatment of rheumatoid arthritis
Authors: Bernier Sylvie G. , Lazarus Douglas D. , Clark Edward , Doyle Beth , Labenski Matthew T. , Thompson Charles D. , Westlin William F. , Hannig Gerhard
Published: July 2004

The hallmark of rheumatoid arthritis (RA) is the progressive destruction of articular joints, characterized by invasive synovial hyperplasia and pathological neovascularization. Here we report that PPI-2458, a member of the fumagillin class of irreversible methionine aminopeptidase-2 (MetAP-2) inhibitors, potently inhibits the proliferation of human fibroblast-like synoviocytes (HFLS-RA), derived from RA patients, with a growth inhibitory concentration 50 (GI50) of 0.04 nM and a maximum inhibition of >95% at 1 nM. Human umbilical vein endothelial cells (HUVEC) are similarly inhibited in proliferation by PPI-2458 (GI50, 0.2 nM). We developed a method to measure the level of MetAP-2 enzyme inhibition after exposure to PPI-2458 and demonstrate that growth inhibition of PPI-2458-sensitive HFLS-RA and HUVEC is linked to MetAP-2 enzyme inhibition, in a dose-dependent fashion. The secretion of several inflammatory mediators such as IL-6 and vascular endothelial growth factor from activated HFLS-RA was not inhibited by PPI-2458. The CNS toxicity profile of PPI-2458, determined by the incidence of seizures, is significantly improved over that of the parental compound TNP-470. In the rat model of peptidoglycan–polysaccharide-induced arthritis, PPI-2458 significantly attenuated paw swelling when therapeutically administered after the onset of chronic disease. We suggest that the mechanism of PPI-2458 action, highly selective and potent anti-proliferative activity on HFLS-RA and HUVECin vitro, a significantly improved CNS toxicity profile, and marked attenuation of chronic disease in the rat peptidoglycan–polysaccharide arthritis modelin vivo, positions this compound as a drug for the treatment of RA.
The
Arabidopsis AtRAD51
gene is dispensable for vegetative development but required for meiosis
Authors: Li Wuxing , Chen Changbin , Markmann-Mulisch Ullrich , Timofejeva Ljudmilla , Schmelzer Elmon , Ma Hong , Reiss Bernd
Published: July 2004

The maintenance of genome integrity and the generation of biological diversity are important biological processes, and both involve homologous recombination. In yeast and animals, homologous recombination requires the function of the RAD51 recombinase. In vertebrates, RAD51 seems to have acquired additional functions in the maintenance of genome integrity, and
rad51
mutations cause lethality, but it is not clear how widely these functions are conserved among eukaryotes. We report here a loss-of-function mutant in the
Arabidopsis
homolog of
RAD51
,
AtRAD51
. The
atrad51
-
1
mutant exhibits normal vegetative and flower development and has no detectable abnormality in mitosis. Therefore, AtRAD51 is not necessary under normal conditions for genome integrity. In contrast,
atrad51
-
1
is completely sterile and defective in male and female meioses. During mutant prophase I, chromosomes fail to synapse and become extensively fragmented. Chromosome fragmentation is suppressed by
atspo11
-
1
, indicating that AtRAD51 functions downstream of AtSPO11-1. Therefore, AtRAD51 likely plays a crucial role in the repair of DNA double-stranded breaks generated by AtSPO11-1. These results suggest that RAD51 function is essential for chromosome pairing and synapsis at early stages in meiosis in
Arabidopsis
. Furthermore, major aspects of meiotic recombination seem to be conserved between yeast and plants, especially the fact that chromosome pairing and synapsis depend on the function of SPO11 and RAD51.