bluuebunny/crossref_metadata_2025 huggingface dataset:
Inhibition of nuclear-protein phosphorylation in vitro by beryllium
Authors: Williams Betsan E. , Skilleter David N.
Published: February 2005

Endogenous cyclic-nucleotide-independent protein phosphorylation by ATP at pH 6.5 in adult rat liver nuclei in vitro is inhibited by beryllium (Be2+), but under the same conditions nuclear-protein dephosphorylation appears to be insensitive to Be2+. Prior incubation of nuclei with Be2+ is necessary to demonstrate the inhibition of phosphorylation, which increases as the pH is decreased from pH 8.0 to 6.5. The extent of inhibition can be related to the level of nuclear Be2+ binding and, evidence suggests, may be caused by direct or indirect interference by Be2+ with Mg2+ binding sites normally required to facilitate protein phosphorylation.
Location in the yeast hexokinase structure of residues related to the enzyme activity
Authors: Gray Andrew J. W. , Barron Nicola M. , Barnard Eric A.
Published: February 2005

Seven residues implicated as acting directly in substrate binding in yeast hexokinase B have been identified in the crystallographic structure by chemical sequencing. The cysteine which is regarded as a residue critically maintaining the active conformation of yeast hexokinase has been selectively labelled and likewise located in the structure. In some parts of the amino acid sequence predicted from the high-resolution electron density map it is found that alignments of chemically sequenced peptides can be made unambiguously; however, the extent of matching to the predicted sequence varies considerably along the chain.
Visible fibrinolysis by endothelial cells: Effect of vitamins and sterols
Authors: Kojima Soichi , Soga Wakako , Hagiwara Hiromi , Shimonaka Motoyuki , Saito Yuji , Inada Yuji
Published: February 2005

We have succeeded in corroborating the enhancing effect of vitamin A, vitamin C, sitosterol and fucosterol on the fibrinolytic activity of endothelial cells. The assay system consisted of an in situ dissolution of a fibrin layer coated onto a culture dish, over which endothelial cells were grown in a culture medium containing 10 % serum. The dissolution was enhanced by the addition of these vitamins and phytosterols to the culture medium.
Heterotopic Neurons in the Umbilical Cord
Authors: Drut Ricardo , Quijano Graciela
Published: February 2005

Several types of tissues have been reported to present ectopically in the umbilical cord (UC). Most of these are found in the UC proximal to the fetus. Featuring tissues are developmentally related to the area, thus representing vestigial remnants. In this report we describe the recognition of neurons and nerves within the UC in a stillborn with several malformations, an observation that we did not find in the literature.
Laminar Necrosis of Placental Membranes: A Histologic Sign of Uteroplacental Hypoxia
Authors: Stanek Jerzy , Al-Ahmadie Hikmat A.
Published: February 2005

Laminar necrosis of placental membranes (LN), a band of coagulative necrosis at the choriodecidual interphase, is a histologic lesion of unclear pathogenesis that has been reported in placentas from preeclampsia, preterm premature rupture of membranes, and preterm abruption. To better explore other possible correlations of LN, we performed a retrospective case-control study in which data on pregnancy risks and outcomes, neonate conditions, and placental gross, routine microscopic, and selected immunohistochemistry examinations in 52 consecutive cases of LN were compared with 52 gestational age-matched control cases without LN. Maternal hypertensive disorders and combinations of 2 or more maternal, fetal, neonatal, or placental conditions known to be potentially associated with uteroplacental hypoxia were more prevalent in patients with LN than in control patients. By immunohistochemistry, LN areas were positive for complement 9 (marker of necrosis) and negative for active caspase 3 (marker of irreversible apoptosis), nitrotyrosine residues (marker of oxidative stress), and Ki-67 (proliferation marker), thus confirming their necrotic rather than apoptotic nature. However, LN areas were flanked by caspase 3 positivity, and the positivity for nitrotyrosine residues was more pronounced in the decidua and mesenchyme in the same membrane rolls as LN, which indicates a probable role of apoptosis and oxidative stress in the development of LN. Based on these immunohistochemical results and clinicopathologic correlations, we believe LN should be recognized and reported as a hypoxic placental lesion.
Increasing fat in the diet does not improve muscle performance in patients with mitochondrial myopathy due to complex I deficiency
Authors: de Meer K. , Roef M. J. , de Klerk J. B. C. , Bakker H. D. , Smit G. P. A. , Poll‐The B. T.
Published: February 2005

Four myopathic patients with complex I deficiency followed diets containing 55 energy per cent (En%) as fat or 25 En% as fat, both for three weeks. Maximal workload and muscle force were not different on either diet. Exercise endurance time, oxygen consumption and lactate levels were also not different, but one patient had diminished endurance time on 25 En% as fat. Our observations do not support the use of increasing the fat in the diet of patients with mitochondrial complex I deficiency.
Monitoring enzyme replacement therapy in Fabry disease—Role of urine globotriaosylceramide
Authors: Whitfield P. D. , Calvin J. , Hogg S. , O'Driscoll E. , Halsall D. , Burling K. , Maguire G. , Wright N. , Cox T. M. , Meikle P. J. , Deegan P. B.
Published: February 2005

Anderson‐Fabry disease (referred to as Fabry disease) is an X‐linked disorder characterized by a deficiency of the lysosomal enzyme α‐galactosidase A and the subsequent accumulation in various tissues of globotriaosylceramide (Gb3), the main substrate of the defective enzyme. Enzyme replacement therapy (ERT) offers a specific treatment for patients with Fabry disease, though monitoring of treatment is hampered by a lack of surrogate markers of response. In this study, the efficacy of long‐term ERT in six Fabry hemizygotes and two symptomatic heterozygotes has been evaluated. Patients were administered recombinant α‐galactosidase A every 2 weeks for up to a year. The efficacy of ERT was assessed by monitoring symptomatology and renal function. Urinary glycolipid concentration was estimated by a novel tandem mass spectrometric method. Urine glycolipid (Gb3) was elevated at baseline and fell impressively on ERT where patients were hemizygotes and in the absence of renal transplantation. In heterozygotes and in a recipient of a renal allograft, elevations and changes in urine glycolipids were less pronounced. In one patient, after several months of ERT, there was a transient increase in Gb3 concentrations to baseline (pre‐ERT) levels, associated with the presence of antibodies to the recombinant α‐galactosidase A. The marked decline in urine Gb3 on ERT, and its subsequent increase in association with an inhibitory antibody response, suggest that this analyte deserves further investigation as a potential marker of disease severity and response to treatment.
Preimplantation diagnosis of a lysosomal storage disorder by in situ enzymatic activity: ‘Proof of principle’ in acid sphingomyelinase‐deficient mice
Authors: Butler A. , Henderson S. C. , Gordon R. E. , Dagan A. , Gatt S. , Schuchman E. H.
Published: February 2005

Genetic diagnosis of preimplantation embryos (PGD) can substantially reduce the chance that at‐risk couples have children afflicted with inherited diseases. However, PGD requires DNA,which is usually obtained from single cells following embryo biopsy. In addition, PGD requires that the genetic defect(s) causing the disorder be known. We have therefore developed an alternative to PGD, which we term preimplantation enzymatic diagnosis (PED). PED has several advantages over PGD, including the facts that it does not require embryo biopsy and that the gene defect(s) causing the disorder need not be known. We have demonstrated ‘proof of principle’ for this approach using embryos obtained from a mouse model (ASMKO mice) of acid sphingomyelinase (ASM)‐deficient Niemann‐Pick disease, an inherited lysosomal storage disorder. For this technique, fluorescently (BODIPY)‐conjugated sphingomyelin was used to detect ASM activity in situ. Wild‐type, preimplantation embryos degraded the substrate following a short ‘pulse‐chase’ period, resulting in markedly reduced fluorescence compared to ASMKO embryos, which retained the fluorescent substrate. Thus, the two embryo types could be easily distinguished by fluorescent microscopy. The fluorescent sphingomyelin was not toxic to the embryos, and the entire procedure could be accomplished within 48 h without embryo biopsy. We suggest that PED may be useful for the preimplantation diagnosis of lysosomal storage disorders, and perhaps other enzymatic defects where similar in situ assay methods are available.
Screening for Menkes disease using the urine HVA/VMA ratio
Authors: Matsuo M. , Tasaki R. , Kodama H. , Hamasaki Y.
Published: February 2005

Menkes disease is a disorder of copper transport that results in early death. Early therapy with parenteral copper‐histidine has been shown to markedly improve outcomes. However, early diagnosis is difficult because patients are asymptomatic in early infancy. In Menkes disease, impaired activity of dopamine β‐hydroxylase, a copper‐dependent enzyme, leads to increased urine ratios of homovanillic acid/vanillylmandelic acid (HVA/VMA). Urine HVA/VMA ratios ranged from 4.1 to 69.7 among 15 patients with Menkes disease, whereas only 0.18% of controls had ratios greater than 4.0. Thus, the urine HVA/VMA ratio is a useful screening method for Menkes disease.
Severe hyperhomocysteinaemia and 5‐oxoprolinuria secondary to antiproliferative and antimicrobial drug treatment
Authors: Schwahn B. , Kameda G. , Wessalowski R. , Mayatepek E.
Published: February 2005

A hitherto healthy 7‐year‐old girl underwent antiproliferative and antibiotic treatment owing to the diagnosis of T‐cell lymphoma and concomitant bacterial infection. She developed an encephalopathic crisis associated with metabolic acidosis, hyponatraemia and severe hyperhomocysteinaemia and 5‐oxoprolinuria. Laboratory tests normalized completely after recovery. Primary defects in glutathione metabolism could be excluded.
Nonlinear eigenvalues and bifurcation problems for Pucci's operators
Authors: Quaas Alexander , Busca Jérôme , Esteban Maria J.
Published: February 2005

In this paper we extend existing results concerning generalized eigenvalues of Pucci's extremal operators. In the radial case, we also give a complete description of their spectrum, together with an equivalent of Rabinowitz's Global Bifurcation Theorem. This allows us to solve nonlinear equations involving Pucci's operators.
A newly synthetic chromium complex – chromium(phenylalanine)3 improves insulin responsiveness and reduces whole body glucose tolerance
Authors: Yang Xiaoping , Palanichamy Kamalakannan , Ontko Allyn C. , Rao M.N.A. , Fang Cindy X. , Ren Jun , Sreejayan Nair
Published: February 2005

Low‐molecular‐weight organic chromium complexes such as chromium picolinate are often used as dietary supplements to improve insulin sensitivity and to correct dyslipidemia. However, toxicity associated with such chromium compounds has compromised their therapeutic value. The aim of this study was to evaluate the impact of a newly synthesized complex of chromium with phenylalanine, Cr(pa)3 on insulin‐signaling and glucose tolerance. Cr(pa)3 was synthesized by chelating chromium(III) with d‐phenylalanine ligand in aqueous solution. In mouse 3T3‐adipocytes, Cr(pa)3 augmented insulin‐stimulated glucose‐uptake as assessed by a radioactive‐glucose uptake assay. At the molecular level, Cr(pa)3 enhanced insulin‐stimulated phosphorylation of Akt in a time‐ and concentration‐dependent manner without altering the phosphorylation of insulin receptor. Oral treatment with Cr(pa)3 (150 μg/kg/d, for six weeks) in ob/ob(+/+) obese mice significantly alleviated glucose tolerance compared with untreated obese mice. Unlike chromium picolinate, Cr(pa)3 does not cleave DNA under physiological reducing conditions. Collectively, these data suggest that Cr(pa)3 may represent a novel, less‐toxic chromium supplement with potential therapeutic value to improve insulin sensitivity and glycemic control in type II diabetes.
Persistent TNF‐α exposure impairs store operated calcium influx in CD4+ T lymphocytes
Authors: Church Leigh D. , Goodall John E. , Rider David A. , Bacon Paul A. , Young Stephen P.
Published: February 2005

Persistent tumour necrosis factor alpha (TNF‐α) exposure uncouples proximal T‐cell receptor (TCR)‐signalling events. Here, we demonstrate that chronic TNF‐α exposure also attenuates signalling distal to the TCR, by specifically inhibiting Ca2+ influx evoked by thapsigargin in CD4+ T‐cells. Mitogen‐induced Ca2+ responses were impaired in a dose dependent manner, and TCR‐induced Ca2+ responses were also significantly reduced. The impairment of Ca2+ influx strongly correlated with poor function as proliferative responses to both mitogen and anti‐CD3/CD28 stimulation were suppressed. Our findings show that persistent TNF‐α exposure of T‐cells specifically inhibits store operated Ca2+ influx. This may affect gene activation and contribute to the poor T‐cell function in chronic inflammatory disease.
The flexible loop of Bcl‐2 is required for molecular interaction with immunosuppressant FK‐506 binding protein 38 (FKBP38)
Authors: Kang Cong Bao , Tai Jeff , Chia Joel , Yoon Ho Sup
Published: February 2005

Bcl‐2 contains an unusually long loop between the first and the second helices. This loop has been shown to be highly flexible based on NMR and X‐ray crystallographic analyses of this region. Bcl‐2 is regulated at the posttranslational level through phosphorylation of specific residues within the flexible loop. The biological role and posttranslational modifications of the loop of Bcl‐2 is currently unclear. FK‐506 binding protein 38 (FKBP38) has been reported to interact with Bcl‐2, suggesting that FKBP38 could act as a docking molecule to localize Bcl‐2 at the mitochondrial membrane [Shirane, M. and Nakayama, K.I. (2003) Inherent calcineurin inhibitor FKBP38 targets Bcl‐2 to mitochondria and inhibits apoptosis. Nat. Cell Biol. 5, 28–37]. Here, we investigated the molecular interaction between FKBP38 and Bcl‐2, and demonstrated that Bcl‐2 interacts with FKBP38 through the unstructured loop, and the interaction appears to regulate phosphorylation in the loop of Bcl‐2.
A part of ice nucleation protein exhibits the ice‐binding ability
Authors: Kobashigawa Yoshihiro , Nishimiya Yoshiyuki , Miura Kazunori , Ohgiya Satoru , Miura Ai , Tsuda Sakae
Published: February 2005

We generated a recombinant 96‐residue polypeptide corresponding to a sequence Tyr176–Gly273 of ice nucleation protein from Pseudomonas syringae (denoted INP96). INP96 exhibited an ability to shape an ice crystal, whose morphology is highly similar to the hexagonal‐bipyramid generally identified for antifreeze protein. INP96 also showed a non‐linear, concentration‐dependent retardation of ice growth. Additionally, circular dichroism and NMR measurements suggested a local structural construction in INP96, which undergoes irreversible thermal denaturation. These data imply that a part of INP constructs a unique structure so as to interact with the ice crystal surfaces.
SHARP‐2/Stra13/DEC1 as a potential repressor of phosphoenolpyruvate carboxykinase gene expression
Authors: Yamada Kazuya , Ogata-Kawata Hiroko , Matsuura Kaoru , Miyamoto Kaoru
Published: February 2005

The influence of the enhancer of split‐ and hairy‐related protein‐2 (SHARP‐2) transcriptional repressor on the expression of rat phosphoenolpyruvate carboxykinase (PEPCK) gene was examined. When H4IIE cells were treated with epigallocatechin gallate, a green tea constituent, an increase in SHARP‐2 mRNA levels and a decrease in PEPCK mRNA levels were observed. The adenovirus‐mediated overexpression of SHARP‐2 in H4IIE cells and primary cultured rat hepatocytes led to a decrease in the levels of PEPCK mRNA. Finally, when a SHARP‐2 expression plasmid was transiently transfected with various reporter plasmids into MH1C1 cells, the promoter activity of a PEPCK reporter plasmid was specifically decreased. Based on these findings, we conclude that SHARP‐2 is a potential repressor of PEPCK gene expression.
Lysosome destabilization by cytosolic extracts, putative involvement of Ca2+/phospholipase C
Authors: Zhao Hui-fang , Wang Xiang , Zhang Guo-Jiang
Published: February 2005

Lysosomal disintegration is a crucial event for living cells, but mechanisms for the event are still unclear. In this study, we established that the cytosolic extracts could enhance lysosomal osmotic sensitivity and osmotically destabilize the lysosomes. The cytosol also caused the lysosomes to become more swollen in the hypotonic sucrose medium. The results indicate that the cytosol induced an osmotic shock to the lysosomes and an influx of water into the organelle. Since the effects of cytosol on the lysosomes could be abolished by O‐tricyclo[5.2.1.02,6]dec‐9‐yl dithiocarbonate potassium salt (D609), a specific inhibitor of cytosolic phospholipase C (PLC), the PLC might play an important role in the lysosomal osmotic destabilization. The activity of cytosolic PLC and the extent of enzyme latency loss of the cytosol‐treated lysosomes exhibited a similar biphasic dependence on the cytosolic Ca2+ concentration. In addition, the cytosol did not osmotically destabilize the lysosomes until the cytosolic calcium ions rose above 100 nM. It suggests that the destabilization effect of cytosol on the lysosomes is Ca2+‐dependent.
Population genetic structure and history of the long-tailed hake, Macruronus magellanicus, in the SW Atlantic as revealed by mtDNA RFLP analysis
Authors: D'Amato M.E. , Carvalho G.R.
Published: February 2005

The long-tailed hake, Macruronus magellanicus, is widely distributed in the SW Atlantic, and although it is commercially exploited, the extent of genetic structuring remains unclear. The hypothesis of a separate inshore stock as suggested by past biological data in northern Patagonia was tested with RFLP profiles of the mtDNA region ND5/6, in a total of 160 animals from eight locations. Sequence divergence between populations was nil, and all diversity is contained within populations. Despite the lack of geographic structuring in the distribution of haplotypes, the inference of population homogeneity should be taken cautiously owing to the skewed frequency distribution of haplotypes, with one allele accounting for 63% of individuals. A phylogenetic analysis of haplotypes reveals a star-shaped pattern with the presence of two lineages that may represent a population expansion. A rapid turnover of lineages, sweepstake recruitment, rapid expansion, or vulnerability to environmental conditions is not only suggested by the network pattern, but also by the departure from neutrality expectations. However, the role of selection cannot be ruled out until more loci or markers are examined.
Accuracy and precision of radiostereometric analysis in the measurement of three‐dimensional micromotion in a fracture model of the distal radius
Authors: Madanat Rami , Mäkinen Tatu J. , Moritz Niko , Mattila Kimmo T. , Aro Hannu T.
Published: February 2005

The purpose of the current study was to verify the feasibility of radiostereometric analysis (RSA) in monitoring three‐dimensional fracture micromotion in fractures of the distal radius. The experimental set‐up consisted of a simulated model of an extra‐articular Colles' fracture, including metallic beads inserted into the bone on either side of the fracture site. The model was rigidly fixed to high precision micrometer stages allowing controlled translation in three axes and rotation about the longitudinal and transverse axes. The whole construct was placed inside a RSA calibration cage with two perpendicular radiographic film cassettes. Accuracy was calculated as the 95% prediction intervals from the regression analyses between the micromotion measured by RSA and actual displacements measured by micrometers. Precision was determined as the standard deviation of five repeated measurements of a 200 μm displacement or a 0.5° rotation along a specific axis. Translations from 25 μm to 5 mm were measured with an accuracy of ±6μm and translations of 200μm were measured with a precision of 2–6 μm. Rotations ranging from 1/6° to 2° were measured with an accuracy of ±0.073° and rotations of 1/2° were measured with a precision of 0.025°–0.096°. The number of markers and their configuration had greater impact on the accuracy and precision of rotation than on those of translation. Aside from the unknown rate of clinical marker loosening, the current results favor the use of at least four markers in each bone fragment in distal radius fractures. These results suggest a strong rationale for the use of RSA as an objective tool for comparing different treatment modalities and novel bone graft substitutes aimed at stabilization of fractures of the distal radius. © 2004 Orthopaedic Research Society. Published by Elsevier Ltd. All rights reserved.
Long‐term ovariectomy decreases ovine compact bone viscoelasticity
Authors: Les C. M. , Vance J. L. , Christopherson G. T. , Turner A. S. , Divine G. W. , Fyhrie D. P.
Published: February 2005

Changes in bone mineral density associated with estrogen depletion in humans do not account for all of the associated change in fracture risk, and it is possible that some of this variation may lie in changes of other aspects of bone quality. The purpose of this study was to investigate changes in viscoelastic behavior of compact bone that may be associated with estrogen depletion. Changes in compact bone viscoelastic properties associated with three years of ovariectomy were investigated with dynamic mechanical analysis (low‐amplitude 3‐point bending at frequencies of 1–20 Hz) using beams milled from the diaphysis of the ovine radius. The viscoelastic storage modulus was significantly (5.2%) lower at the higher frequencies for the ovariectomized animals. The general anatomic variation in storage modulus, in which cranial sectors had higher values than caudal sectors, did not change with ovariectomy. The loss tangent (tan δ, a measure of damping) was also greatly decreased (up to 83%) at high frequencies in the ovariectomized animals. Anatomic variation in tan δ at low (6–12 Hz) frequencies (cranial and caudal sectors having higher values than lateral or medial sectors) was enhanced with ovariectomy. Changes in viscoelastic properties associated with long term estrogen depletion could be responsible for a significant reduction in the toughness or strength of a bone without concomitant changes in screening modalities used to evaluate bone quality (e.g., DXA, QCT, QUA). © 2005 Orthopaedic Research Society. Published by Elsevier Ltd. All rights reserved.
Cosmogenic nuclide evidence for low weathering and denudation in the wet, tropical highlands of Sri Lanka
Authors: von Blanckenburg Friedhelm , Hewawasam Tilak , Kubik Peter W.
Published: February 2005

Some of the lowest weathering and erosion rates in any mountain range in the world have been measured using cosmogenic nuclides in the steep, humid, tropical highlands of Sri Lanka. The total preanthropogenic denudation rates were measured in creek sediments and soil samples from unperturbed rain forest sites, bedrock from mountain crests, and bedrock from inselbergs. Denudation rates are in the range of 5–30 t km−2 yr−1 (2–11 mm ky−1). These rates average denudation over the last 50–250 ky. Weathering exports in rivers draining the mountainous Central Highlands show that silicate weathering rates are also low, varying from 5 to 20 t km−2 yr−1 today (2–7 mm ky−1), but they represent a significant fraction of the total denudation. All these observations run contrary to the conventional geomorphologic and geochemical wisdom that would predict rapid erosion for highlands of high relief, temperatures, and precipitation. We speculate that the high relief in Sri Lanka represents the remnant of a geomorphic block that was uplifted during rifting at 130 Ma or even earlier and that was reduced to the interior of the island by rapid receding of escarpments after continental breakup. It is possible that throughout this history, hillslopes, where not exposing bare bedrock, were protected by thick weathered profiles. Such clay‐rich layers would inhibit silicate weathering by shielding bedrock from weathering agents. In the absence of landscape rejuvenation, physical erosion rates are low, and fresh mineral surfaces are not being supplied. The observation that wet, steep, tropical highlands can have low rates of rock weathering and erosion has some potentially profound implications for the long‐term controls of atmospheric CO2 budgets: High temperature and precipitation, which are much invoked though controversial agents for silicate dissolution and CO2 drawdown, become ineffective in promoting weathering in areas that are not tectonically active.
Radiometric ages for basement rocks from the Emperor Seamounts, ODP Leg 197
Authors: Duncan Robert A. , Keller Randall A.
Published: February 2005

The Hawaiian‐Emperor seamount chain is the “type” example of an age‐progressive, hot spot‐generated intraplate volcanic lineament. However, our current knowledge of the age distribution within this province is based largely on radiometric ages determined several decades ago. Improvements in instrumentation, sample preparation methods, and new material obtained by recent drilling warrant a reexamination of the age relations among the older Hawaiian volcanoes. We report new age determinations (40Ar‐39Ar incremental heating method) on whole rocks and feldspar separates from Detroit (Sites 1203 and 1204), Nintoku (Site 1205), and Koko (Site 1206) Seamounts (Ocean Drilling Program (ODP) Leg 197) and Meiji Seamount (Deep Sea Drilling Project (DSDP) Leg 19, Site 192). Plateaus in incremental heating age spectra for Site 1203 lava flows give a mean age of 75.8 ± 0.6 (2σ) Ma, which is consistent with the normal magnetic polarity directions observed and biostratigraphic age assignments. Site 1204 lavas produced discordant spectra, indicating Ar loss by reheating and K mobilization. Six plateau ages from lava flows at Site 1205 give a mean age of 55.6 ± 0.2 Ma, corresponding to Chron 24r. Drilling at Site 1206 intersected a N‐R‐N magnetic polarity sequence of lava flows, from which six plateau ages give a mean age of 49.1 ± 0.2 Ma, corresponding to the Chron 21n‐22r‐22n sequence. Plateau ages from two feldspar separates and one lava from DSDP Site 192 range from 34 to 41 Ma, significantly younger than the Cretaceous age of overlying sediments, which we relate to postcrystallization K mobilization. Combined with new dating results from Suiko Seamount (DSDP Site 433) and volcanoes near the prominent bend in the lineament [Sharp and Clague, 2002], the overall trend is increasing volcano age from south to north along the Emperor Seamounts, consistent with the hot spot model. However, there appear to be important departures from the earlier modeled simple linear age progression, which we relate to changes in Pacific plate motion and the rate of southward motion of the Hawaiian hot spot.
“Yin‐Yang grid”: An overset grid in spherical geometry
Authors: Kageyama Akira , Sato Tetsuya
Published: February 2005

A new kind of overset grid, named Yin‐Yang grid, for spherical geometry is proposed. The Yin‐Yang grid is composed of two identical component grids that are combined in a complemental way to cover a spherical surface with partial overlap on their boundaries. Each component grid is a low‐latitude part of the latitude‐longitude grid. Therefore the grid spacing is quasi‐uniform, and the metric tensors are simple and analytically known. One can directly apply mathematical and numerical resources that have been written in the spherical polar coordinates or latitude‐longitude grid. The complemental combination of the two identical component grids enables us to make efficient and concise programs. Simulation codes for geodynamo and mantle convection simulations using finite difference scheme based on the Yin‐Yang grid are developed and tested. The Yin‐Yang grid is suitable for massively parallel computers.
Accurate measurement of volcanic SO2 flux: Determination of plume transport speed and integrated SO2 concentration with a single device
Authors: McGonigle A. J. S. , Inguaggiato S. , Aiuppa A. , Hayes A. R. , Oppenheimer C.
Published: February 2005

Ground‐based measurements of volcanic sulfur dioxide fluxes are important indicators of volcanic activity, with application in hazard assessment, and understanding the impacts of volcanic emissions upon the environment and climate. These data are obtained by making traverses underneath the volcanic plume a few kilometers from source with an ultraviolet spectrometer, measuring integrated SO2 concentrations across the plume's cross section, and multiplying by the plume's transport speed. However, plume velocities are usually derived from ground‐based anemometers, located many kilometers from the traverse route and hundreds of meters below plume altitude, complicating the experimental design and introducing large flux (can be >100%) errors. Here we present the first report of a single instrument capable of (accurate) volcanic SO2 flux measurements. This device records integrated SO2 concentrations and plume heights during traverses. Between traverses, two in‐plume SO2 time series are measured from underneath the plume with the instrument, corresponding to zenith and inclined (user‐specified angle from vertical in the direction of the volcano) fields of view, respectively. The distance between the points of intersection of the two views with the plume is found on the basis of the determined plume height, and the two signals are cross‐correlated to determine the lag between them, enabling accurate derivation of the wind speed. We present flux data (with errors ≈±12%) obtained in this way at Mt. Etna during July 2004.
Satellite ballistic coefficients and the lower thermosphere
Authors: Bhatnagar V. P. , Germany G. A. , Tan A.
Published: February 2005

Observed variations in the estimated ballistic coefficients (B′) for satellites in the lower thermosphere during 2001, have been used to study its implications for atmospheric densities with respect to changes in the solar and geomagnetic activities. It is shown that the steady state density models predict the true densities within 10% as a function of solar activity, except during strong geomagnetic storms, when true densities are underestimated by about 15%. The variations in B′ with days point to a semiannual variation (SAV) in the scaling factor required to correctly predict SAV in the true densities from steady state models. The calculations also show that changes in density ratios during some major geomagnetic storms can not be explained by steady state models. The Ncar‐Tigcm models may be used to see if these bring B′ closer to true ballistic coefficients than the steady state models.
Subpixel burn detection in Moderate Resolution Imaging Spectroradiometer 500‐m data with ARTMAP neural networks
Authors: Shabanov N. V. , Lo K. , Gopal S. , Myneni R. B.
Published: February 2005

This paper presents an ARTMAP neural network approach for burn detection in Moderate Resolution Imaging Spectroradiometer (MODIS) data using two methods: discrete and continuous classifications. The study area covers the states of Idaho and Montana in the United States, where extensive fire events took place during the months of July and August in the year 2000. The proposed approach differs from commonly used change detection schemes by utilizing a single surface reflectance image instead of time series of satellite data. Burn detection in this study was accomplished by the classification of land into four classes: burns, woody vegetation, herbaceous vegetation, and barren. We performed the discrete classification of coarse (500‐m MODIS data) and high‐resolution (30‐m Enhanced Thematic Mapper (ETM+) data) surface reflectance data with an ARTMAP classifier to evaluate the impact of a land cover mixture on burn detection. The analysis of classification results reveals commission and omission errors in the evaluation of burn area extent at a coarse‐resolution scale. To account for land cover heterogeneity, we utilized the continuous classification of coarse‐resolution data with an ARTMAP mixture model. A training data set on the land cover mixture at 500‐m scale of MODIS data was assembled from the aggregated 30‐m ETM+ classification. The ARTMAP mixture model was trained with MODIS surface reflectance data and land cover mixture information to generate a continuous classification of burns (expressed in percentage of burns per pixel). Data fusion of coarse‐ and high‐resolution satellite data in this study resulted in a more natural and accurate mapping of burns as mixtures with other land cover types.
The Maastrichtian record from Shatsky Rise (northwest Pacific): A tropical perspective on global ecological and oceanographic changes
Authors: Frank Tracy D. , Thomas Deborah J. , Leckie R. Mark , Arthur Michael A. , Bown Paul R. , Jones Kelly , Lees Jackie A.
Published: February 2005

We present new isotopic and micropaleontological data from a depth transect on Shatsky Rise that record the response of the tropical Pacific to global biotic and oceanographic shifts during the mid‐Maastrichtian. Results reveal a coupling between the upper ocean, characterized by a weak thermocline and low to intermediate productivity, and intermediate waters. During the earliest Maastrichtian, oxygen and neodymium isotope data suggest a significant contribution of relatively warm intermediate water from the North Pacific. Isotopic shifts through the early Maastrichtian suggest that this warmer water mass was gradually replaced by cooler waters originating in the Southern Ocean. Although the cooler water mass remained dominant through the remainder of the Maastrichtian, it was displaced intermittently at shallow intermediate depths by North Pacific intermediate water. The globally recognized “mid‐Maastrichtian event” ∼69 Ma, manifested by the brief appearance of abundant inoceramid bivalves over shallow portions of Shatsky Rise, is characterized by an abrupt increase (∼2°–3°C) in sea surface temperatures, a greater flux of organic matter out of the surface ocean, and warmer (∼4°C) intermediate waters. Results implicate simultaneous changes in surface waters and the sources/distribution patterns of intermediate water masses as an underlying cause for widespread biotic and oceanographic changes during mid‐Maastrichtian time.
Space Weather Research to Benefit From IGY Anniversary
Authors: Simpson Sarah
Published: February 2005

Retrieving new records of past solar activity and increasing access to current observations of the space environment are among plans to honor the 50th anniversary of the International Geophysical Year
Homogenization of Richards equation in permeability fields with different connectivities
Authors: Neuweiler Insa , Cirpka Olaf A.
Published: February 2005

Large‐scale modeling of transient flow in the unsaturated zone is important for the estimation of the water budget and solute transport in the vadose zone. Upscaled flow models need to capture the impact of small‐scale heterogeneities, which are not resolved by the model, on large‐scale flow. We perform upscaling of the Richards equation in heterogeneous porous media with continuous distributions of the soil hydraulic parameters using homogenization theory and stochastic averaging techniques. We restrict the analysis to flow regimes in which the capillary‐equilibrium assumption holds on the small scale. In order to account for effects of capillary entry pressure we apply the Brooks‐Corey model for the soil retention and relative permeability curves and consider Leverett scaling for the coupling of intrinsic permeability and entry pressure. For this model we derive and analyze the ensemble‐averaged parameter functions for the macroscopic flow equations. The effects of a definite entry pressure vanish with increasing variance of the log intrinsic permeability. We compare the statistically averaged parameter functions to numerically calculated effective functions for parameter fields with different connectivity properties. These results illustrate that soils with well‐connected coarse materials differ in the relative permeability from those with well‐connected fine materials or those without particular connectedness.
The ADAMTS metalloproteinases
Authors: PORTER Sarah , CLARK Ian M. , KEVORKIAN Lara , EDWARDS Dylan R.
Published: February 2005

The ADAMTSs (adisintegrin and metalloproteinase with thrombospondin motifs) are a group of proteases that are found both in mammals and invertebrates. Since the prototype ADAMTS-1 was first described in 1997, there has been a rapidly expanding body of literature describing this gene family and the proteins they encode. The complete human family has 19 ADAMTS genes, together with three members of a newly identified subgroup, the ADAMTSL (ADAMTS-like) proteins, which have several domains in common with the ADAMTSs. The ADAMTSs are extracellular, multidomain enzymes whose known functions include: (i) collagen processing as procollagen N-proteinase; (ii) cleavage of the matrix proteoglycans aggrecan, versican and brevican; (iii) inhibition of angiogenesis; and (iv) blood coagulation homoeostasis as the von Willebrand factor cleaving protease. Roles in organogenesis, inflammation and fertility are also apparent. Recently, some ADAMTS genes have been found to show altered expression in arthritis and various cancers. This review highlights progress in understanding the structural organization and functional roles of the ADAMTSs in normal and pathological conditions.
Characterization of the polyene macrolide P450 epoxidase from Streptomyces natalensis that converts de-epoxypimaricin into pimaricin
Authors: MENDES Marta V. , ANTÓN Nuria , MARTÍN Juan F. , APARICIO Jesús F.
Published: February 2005

The biosynthesis of the antifungal agent pimaricin by Streptomyces natalensis has been proposed to involve a cytochrome P450 encoded by the gene pimD. Pimaricin is derived from its immediate precursor de-epoxypimaricin by epoxidation of the C-4–C-5 double bond on the macrolactone ring. We have overproduced PimD with a N-terminal His6 affinity tag in Escherichia coli and purified the enzyme for kinetic analysis. The protein showed a reduced CO-difference spectrum with a Soret maximum at 450 nm, indicating that it is a cytochrome P450. Purified PimD was shown to catalyse the in vitro C-4–C-5 epoxidation of 4,5-de-epoxypimaricin to pimaricin. The enzyme was dependent on NADPH for activity with optimal pH at 7.5, and the temperature optimum was 30 °C. The kcat value for the epoxidation of de-epoxypimaricin was similar to the values reported for other macrolide oxidases. Enzyme activity was inhibited at high substrate concentration. This is the first time that a polyene macrolide P450 mono-oxygenase has been expressed heterologously and studied. The unique specificity of this epoxidase should be useful for the oxidative modification of novel polyene macrolide antibiotics.
The antagonistic regulation of human MUC4 and ErbB-2 genes by the Ets protein PEA3 in pancreatic cancer cells: implications for the proliferation/differentiation balance in the cells
Authors: FAUQUETTE Valérie , PERRAIS Michael , CERULIS Sylvain , JONCKHEERE Nicolas , DUCOUROUBLE Marie-Paule , AUBERT Jean-Pierre , PIGNY Pascal , SEUNINGEN Isabelle Van
Published: February 2005

The human transmembrane mucin MUC4 is aberrantly expressed in 75% of pancreatic ductal adenocarcinomas, whereas no expression is found in normal pancreas. Therefore MUC4 appears as a useful biological marker for the diagnosis of ductal adenocarcinomas. Since rat Muc4 was shown to interact with ErbB-2 tyrosine kinase receptor and to either promote cell survival and differentiation or cell proliferation, it is postulated that MUC4 may also participate in pancreatic carcinogenesis. Our aim was to investigate in parallel the role of the Ets factor PEA3 in MUC4 and ErbB-2 transcriptional regulation in pancreatic cancer cells. Two MUC4-expressing WD (well-differentiated) (CAPAN-1 and -2) and one MUC4-non-expressing poorly differentiated (PANC-1) cell lines were used. The three cell lines express ErbB-2 at different levels. By co-transfection and site-directed mutagenesis, we show that PEA3 is a transactivator of the MUC4 promoter and that the −216 and −2368 PEA3 binding sites of the MUC4 promoter are essential. We also demonstrate that PEA3 acts in synergy with c-Jun and specificity protein 1 to transactivate the proximal region of the MUC4 promoter and increase MUC4 mRNA levels in WD cells. These results suggest that MUC4 is a new target gene of the Ets factor PEA3 in pancreatic cancer cells. In contrast, PEA3 represses the transcriptional activity of two fragments of the ErbB-2 promoter in a dose-dependent manner and decreases the endogenous ErbB-2 mRNA levels in WD cell lines. Thus, PEA3, by its capacity to up-regulate the epithelial marker MUC4 and to down-regulate the ErbB-2 oncogene, appears as a key regulator of the differentiation/proliferation balance in pancreatic cancer cells.
PARP inhibition sensitizes p53-deficient breast cancer cells to doxorubicin-induced apoptosis
Authors: MUÑOZ-GÁMEZ José Antonio , MARTÍN-OLIVA David , AGUILAR-QUESADA Rocío , CAÑUELO Ana , NUÑEZ M. Isabel , VALENZUELA M. Teresa , RUIZ de ALMODÓVAR J. M. , de MURCIA Gilbert , OLIVER F. Javier
Published: February 2005

p53 deficiency confers resistance to doxo (doxorubicin), a clinically active and widely used antitumour anthracycline antibiotic. The purpose of the present study was to investigate the reversal mechanism of doxo resistance by the potent PARP [poly(ADP-ribose) polymerase] inhibitor ANI (4-amino-1,8-naphthalimide) in the p53-deficient breast cancer cell lines EVSA-T and MDA-MB-231. The effects of ANI, in comparison with doxo alone, on doxo-induced apoptosis, were investigated in matched pairs of EVSA-T or MDA-MB-231 with or without ANI co-treatment. Doxo elicited PARP activation as determined by Western blotting and immunofluorescence of poly(ADP-ribose), and ANI enhanced the cytotoxic activity of doxo 2.3 times and in a caspase-dependent manner. The long-term cytotoxic effect was studied by a colony-forming assay. Using this assay, ANI also significantly potentiates the long-term cytotoxic effect with respect to treatment with doxo alone. Decrease in mitochondrial potential together with an increase in cytochrome c release, association of Bax with the mitochondria and caspase 3 activation were also observed in the presence of ANI. Therefore PARP inhibition may represent a novel way of selectively targeting p53-deficient breast cancer cells. The underlying mechanism is probably a potentiation of unrepaired DNA damage, shifting from DNA repair to apoptosis due to the effective inhibition of PARP activity.
Specific interactions of PP2A and PP2A-like phosphatases with the yeast PTPA homologues, Ypa1 and Ypa2
Authors: Van HOOF Christine , MARTENS Ellen , LONGIN Sari , JORDENS Jan , STEVENS Ilse , JANSSENS Veerle , GORIS Jozef
Published: February 2005

To elucidate the specific biological role of the yeast homologues of PTPA (phosphatase 2A phosphatase activator), Ypa1 and Ypa2 (where Ypa stands for yeast phosphatase activator), in the regulation of PP2A (protein phosphatase 2A), we investigated the physical interaction of both Ypa proteins with the catalytic subunit of the different yeast PP2A-like phosphatases. Ypa1 interacts specifically with Pph3, Sit4 and Ppg1, whereas Ypa2 binds to Pph21 and Pph22. The Ypa1 and Ypa2 proteins do not compete with Tap42 (PP2A associating protein) for binding to PP2A family members. The interaction of the Ypa proteins with the catalytic subunit of PP2A-like phosphatases is direct and independent of other regulatory subunits, implicating a specific function for the different PP2A–Ypa complexes. Strikingly, the interaction of Ypa2 with yeast PP2A is promoted by the presence of Ypa1, suggesting a positive role of Ypa1 in the regulation of PP2A association with other interacting proteins. As in the mammalian system, all yeast PP2A-like enzymes associate as an inactive complex with Yme (yeast methyl esterase). Ypa1 as well as Ypa2 can reactivate all these inactive complexes, except Pph22-Yme. Ypa1 is the most potent activator of PP2A activity, suggesting that there is no direct correlation between activation potential and binding capacity.
The expression of the human neuronal α3 Na+,K+-ATPase subunit gene is regulated by the activity of the Sp1 and NF-Y transcription factors
Authors: BENFANTE Roberta , ANTONINI Ruth Adele , VACCARI Monica , FLORA Adriano , CHEN Fabian , CLEMENTI Francesco , FORNASARI Diego
Published: February 2005

The Na+,K+-ATPase is a ubiquitous protein found in virtually all animal cells which is involved in maintaining the electrochemical gradient across the plasma membrane. It is a multimeric enzyme consisting of α, β and γ subunits that may be present as different isoforms, each of which has a tissue-specific expression profile. The expression of the Na+,K+-ATPase α3 subunit in humans is confined to developing and adult brain and heart, thus suggesting that its catalytic activity is strictly required in excitable tissues. In the present study, we used structural, biochemical and functional criteria to analyse the transcriptional mechanisms controlling the expression of the human gene in neurons, and identified a minimal promoter region of approx. 100 bp upstream of the major transcription start site which is capable of preferentially driving the expression of a reporter gene in human neuronal cell lines. This region contains the cognate DNA sites for the transcription factors Sp1/3/4 (transcription factors 1/3/4 purified from Sephacryl and phosphocellulose columns), NF-Y (nuclear factor-Y) and a half CRE (cAMP-response element)-like element that binds a still unknown protein. Although the expression of these factors is not tissue-specific, co-operative functional interactions among them are required to direct the activity of the promoter predominantly in neuronal cells.
Essential tension and constructive destruction: the spindle checkpoint and its regulatory links with mitotic exit
Authors: TAN Agnes L. C. , RIDA Padmashree C. G. , SURANA Uttam
Published: February 2005

Replicated genetic material must be partitioned equally between daughter cells during cell division. The precision with which this is accomplished depends critically on the proper functioning of the mitotic spindle. The assembly, orientation and attachment of the spindle to the kinetochores are therefore constantly monitored by a surveillance mechanism termed the SCP (spindle checkpoint). In the event of malfunction, the SCP not only prevents chromosome segregation, but also inhibits subsequent mitotic events, such as cyclin destruction (mitotic exit) and cytokinesis. This concerted action helps to maintain temporal co-ordination among mitotic events. It appears that the SCP is primarily activated by either a lack of occupancy or the absence of tension at kinetochores. Once triggered, the inhibitory circuit bifurcates, where one branch restrains the sister chromatid separation by inhibiting the E3 ligase APCCdc20 (anaphase-promoting complex activated by Cdc20) and the other impinges on the MEN (mitotic exit network). A large body of investigations has now led to the identification of the control elements, their targets and the functional coupling among them. Here we review the emerging regulatory network and discuss the remaining gaps in our understanding of this effective mechanochemical control system.