bluuebunny/crossref_metadata_2025 huggingface dataset:
Nonstructural Protein 3 of Bluetongue Virus Assists Virus Release by Recruiting ESCRT-I Protein Tsg101
Authors: Wirblich Christoph , Bhattacharya Bishnupriya , Roy Polly
Published: December 2005

The release ofBluetongue virus(BTV) and other members of theOrbivirusgenus from infected host cells occurs predominantly by cell lysis, and in some cases, by budding from the plasma membrane. Two nonstructural proteins, NS3 and NS3A, have been implicated in this process. Here we show that both proteins bind to human Tsg101 and its ortholog fromDrosophila melanogasterwith similar strengths in vitro. This interaction is mediated by a conserved PSAP motif in NS3 and appears to play a role in virus release. The depletion of Tsg101 with small interfering RNA inhibits the release of BTV and African horse sickness virus, a related orbivirus, from HeLa cells up to fivefold and threefold, respectively. Like most other viral proteins which recruit Tsg101, NS3 also harbors a PPXY late-domain motif that allows NS3 to bind NEDD4-like ubiquitin ligases in vitro. However, the late-domain motifs in NS3 do not function as effectively in facilitating the release of mini Gag virus-like particles from 293T cells as the late domains from human immunodeficiency virus type 1, human T-cell leukemia virus, and Ebola virus. A mutagenesis study showed that the arginine residue in the PPRY motif is responsible for the low activity of the NS3 late-domain motifs. Our data suggest that the BTV late-domain motifs either recruit an antagonist that interferes with budding or fail to recruit an agonist which is different from NEDD4.
The Herpes Simplex Virus Type 1 vhs-UL41 Gene Secures Viral Replication by Temporarily Evading Apoptotic Cellular Response to Infection: Vhs-UL41 Activity Might Require Interactions with Elements of Cellular mRNA Degradation Machinery
Authors: Barzilai Ari , Zivony-Elbom Ifaat , Sarid Ronit , Noah Eran , Frenkel Niza
Published: December 2005

We have previously shown that herpes simplex virus type 1 (HSV-1) infection is associated with early destabilization/degradation of infected cell mRNAs and consequent shutoff of host protein synthesis by the activity of the virion-associated host shutoff (vhs) UL41 protein. Wild-type (wt) virus destabilized/degraded the housekeeping β-actin and α-tubulin mRNAs as well host stress functions, like the heat shock 70 protein induced postinfection. vhs mutants did not degrade the mRNAs. Elaborate studies by others have been concerned with the mode of mRNA degradation and the mRNAs affected. We now describe vhs activity in primary cultures of mouse cerebellar granule neurons (CGNs). Specifically, (i) upon infection in the presence of actinomycin D to test activity of input viral particles, there was a generalized inhibition of protein synthesis, which depended on the input multiplicity of infection (MOI). (ii) Low-MOI infection with vhs-1 mutant virus was associated with increased synthesis of all apparent proteins. Higher MOIs caused some shutoff, albeit significantly lower than that of wt virus. This pattern could reflect an interaction(s) of vhs-1 protein with host machinery involved in cellular mRNA destabilization/degradation, sequestering this activity. (iii) wt virus infection was associated with cell survival, at least for a while, whereas mutant virus induced apoptotic cell death at earlier times. (iv) wt virus replicated well in the CGNs, whereas there was no apparent replication of the vhs-1 mutant virus. (v) The vhs-1 mutant could serve as helper virus for composite amplicon vectors carrying marker genes and the human p53 gene. Ongoing studies test the use of vhs-1-based composite oncolytic vectors towards cancer gene therapy.
Respiratory Syncytial Virus (RSV) Infects Neuronal Cells and Processes That Innervate the Lung by a Process Involving RSV G Protein
Authors: Li Xia-qing , Fu Zhen F. , Alvarez Rene , Henderson Christine , Tripp Ralph A.
Published: December 2005

Respiratory syncytial virus (RSV) is a primary cause of morbidity and life-threatening lower respiratory tract disease in infants and young children. Children with acute RSV bronchiolitis often develop respiratory sequelae, but the disease mechanisms are poorly understood. Mounting evidence suggests that RSV may mediate persistent infection. Using immunohistochemistry to identify RSV and RSV-infected cell types, we show that RSV infects primary neurons and neuronal processes that innervate the lungs through a process that involves RSV G protein and the G protein CX3C motif. These findings suggest a mechanism for disease chronicity and have important implications for RSV disease intervention strategies.
THE IMPACT OF ENVIRONMENTAL STRINGENCY ON THE FOREIGN DIRECT INVESTMENTS OF THE OECD COUNTRIES
Authors: MIHCI HAKAN , CAGATAY SELIM , KOSKA ONUR
Published: December 2005

The main objective of this paper is to evaluate the impact of the environmental stringency on trade and the foreign direct investments (FDI) in particular. To do so, both theoretical and empirical investigations are performed. During the empirical investigation, an index of environmental sensitivity performance (IESP) is constructed for the OECD countries. Additionally, the main determinants of the OECD countries' FDI outflows are also analysed alongside with the environmental sensitivity variable for the countries in the sample.

The empirical analysis in this paper finds some evidence to suggest that environmental stringency has an important impact on the FDI outflows of the OECD countries. The impact of the degree of environmental stringency on the FDI is significantly positive implying a direct relationship between FDI outflows and relative environmental sensitivity performance of the OECD countries.
AMS and grain shape fabric of the Late Palaeozoic diamictites of the Southeastern Paraná Basin, Brazil
Authors: Archanjo C.J. , Silva M.G. , Castro J.C. , Launeau P. , Trindade R.I.F. , Macedo J.W.P.
Published: December 2005

Diamictites interbedded with marine shales and turbidites onlap the eastern border of the Paraná Basin (Southern Brazil). These poorly sorted sediments were deposited during the Permo-Carboniferous glaciation, and their matrix-supported clasts show no preferred orientation. These massive rocks have been studied using anisotropy of magnetic susceptibility (AMS) and grain shape fabric. Hysteresis loops and thermomagnetic measurements show that AMS depends mostly on the paramagnetic clays, but fine ferromagnetic particles also contribute to the anisotropy. The coarse silt to sand grain preferred orientation study supports the use of AMS in describing the diamictite fabric, at least regarding the orientation of the foliation. AMS and grain shape data reveal subhorizontal to weakly inclined magnetic and grain shape foliation parallel to the regional bedding. The magnetic lineations are normally scattered within the foliation plane in agreement with the oblate AMS ellipsoids found in these rocks. Both fabric patterns are consistent with deposition by subaqueous mudflows that were resedimented downslope, with clastic supply from continental sources. The off-vertical grain shape foliation poles suggest that the deposition of diamictites was controlled by the depocentre topography of the Rio do Sul sub-basin.
K–Ar and
40
Ar/
39
Ar geochronology of supergene processes in the Atacama Desert, Northern Chile: tectonic and climatic relations
Authors: Arancibia G. , Matthews S.J. , Pérez de Arce C.
Published: December 2005

New K–Ar and
40
Ar/
39
Ar data obtained for 29 samples of supergene alunite-, jarosite- and hollandite-group minerals from the Central Depression of Northern Chile document almost continuous supergene oxidation from 33 to 9 Ma. The downward migration of supergene oxidation zones is used to calculate maximum denudation rates of 16–35 m Ma
−1
. These calculated rates are sensitive to pre-existing topography and show that the present relief observed in the Central Depression represents a modified Miocene landscape. The results presented here are in good agreement with previously published geochronological data for the Atacama Desert. The combination of all published data, including the results presented here, defines a continuous skewed distribution, with a maximum between 21 and 14 Ma. The relative paucity of ages greater than 30 Ma reflects the removal of supergene profiles by erosion during and immediately after the Incaic compressive deformation. From 29 to 9 Ma, supergene oxidation profiles were generated under semi-arid conditions throughout the Atacama region. Ages between 9 and 5 Ma on the northern and southern margins of the desert mark the end of supergene oxidation processes, consistent with a Pliocene onset of present-day hyperaridity.
Influence of slump folds on tectonic folds: an example from the Lower Ordovician of the Anglo-Brabant Deformation Belt (Belgium)
Authors: Beckers R. , Debacker T.N.
Published: December 2005

Although it is generally accepted that buckle folds will not develop in a perfectly planar layer without the presence of some irregularity or perturbation at which the folds initiate, there are very few cases in which individual natural folds can be linked to specific irregularities. Within the Lower Ordovician Abbaye de Villers Formation, Anglo-Brabant Deformation Belt, metre-scale tectonic folds occur, of which the position and, to a certain extent, the geometry appear to be controlled by slump folds and related features. The metre-scale tectonic folds, interpreted as parasitic structures on the limb of a large-scale host fold, occur only within a stratigraphic level affected by slumping. In this level, tectonic antiforms tend to form superimposed on antiformal slump folds and on zones of abrupt, slump-related thickness increase, and tectonic synforms on synformal slump folds and on zones of abrupt thickness decrease.   The rather irregular 3D geometry of sedimentary sequences suggests that many more similar cases should exist in which folds can be linked to specific irregularities. However, possibly it is also this abundance of irregularities in sedimentary sequences, in combination with fold and outcrop scale, that makes it difficult to attribute a particular fold to a particular perturbation.
Rift-initiation development of normal fault blocks: insights from the Hammam Faraun fault block, Suez Rift, Egypt
Authors: Jackson C.A.L. , Gawthorpe R.L. , Leppard C.W. , Sharp I.R.
Published: December 2005

An integrated structural and stratigraphic study of the Hammam Faraun fault block, Suez Rift, Egypt, provides insights into the rift-initiation tectonostratigraphic evolution of the crustal-scale normal fault blocks. The shallow marine to offshore Tayiba Formation (Lower Oligocene) represents the youngest preserved pre-rift unit, and key stratal surface development indicates that relative sea-level variations exerted a marked control on its stratigraphic evolution. A major sea-level fall, which may have been a regional (i.e. eustatic) event, occurred during the mid-Oligocene and was synchronous with the onset of rifting. A major erosional unconformity (the base synrift unconformity) formed in response to the sea-level fall and defines a series of NNE–SSW- to NE–SW-trending palaeovalleys up to 40 m deep by 500 m wide, which are infilled by continental deposits and volcanic rocks of the Abu Zenima Formation (Upper Oligocene–Lower Miocene). During the rift initiation, palaeovalleys controlled depositional patterns and the evolving fault-controlled topography was insufficient to modify drainage patterns. Through time, however, surface-breaking faults began to exert a marked control on deposition. This study indicates the complexity that can occur during the rift-initiation phase caused by extrabasinal factors such as eustatic sea-level variations and antecedent drainage.
Precise
40
Ar/
39
Ar geochronology for the upper Koobi Fora Formation, Turkana Basin, northern Kenya
Authors: McDougall Ian , Brown Francis H.
Published: December 2005

The Plio-Pleistocene Koobi Fora Formation, about 560 m thick, crops out east of Lake Turkana and is part of the much larger depositional system of the Omo–Turkana Basin. The upper half of the Koobi Fora Formation from just below the KBS Tuff to above the Chari Tuff is particularly notable for its wealth of hominid fossils and archaeological sites. Silicic tuffaceous horizons have provided the basis for stratigraphic subdivision and correlation. Pumice clasts within the tuffs contain anorthoclase phenocrysts, ideal for
40
Ar/
39
Ar single-crystal dating. Feldspars from pumice clasts in about 15 tephra within the stratigraphic interval from the KBS Tuff to the Silbo Tuff have yielded precise ages that allow much finer definition of the numerical time framework for the sedimentary sequence between the KBS Tuff (1.869 ± 0.021 Ma) and the Chari Tuff (1.383 ± 0.028 Ma) and to yet higher in the sequence to the SilboTuff (0.751 ± 0.022 Ma). These results provide a precise and accurate time scale for the upper part of the sequence in the whole of the Omo–Turkana Basin. A number of these tuffs are recognized elsewhere in East Africa; thus ages determined at Koobi Fora also apply to the wider region.
Latest Mid-Pennsylvanian tree-fern forests in retrograding coastal plain deposits, Sydney Mines Formation, Nova Scotia, Canada
Authors: Falcon-Lang H.J.
Published: December 2005

A latest Mid-Pennsylvanian (early Cantabrian) tree-fern forest is reported from Cape Breton Island, Nova Scotia. The fossil forest is rooted below the Point Aconi coal seam of the Sydney Mines Formation at Cranberry Head. The tree-ferns are preserved in the deposits of a coastal plain, subject to brackish incursions. They were constructed of psaronid-type trunks and massive pecopterid fronds, and locally intergrew with sigillarian lycopsids, neuropterid pteridosperms, and calamiteans. Basal stump diameter measurements, including the root mantle, range from 12 to 89 cm, indicating that the ferns were mostly large forest trees, rather than shrubs. Stump distribution measurements on palaeosols indicate that localized patches of tree-fern-dominated forest attained densities of
c
. 3850 trees per hectare when scaled up to standard forestry units, much denser than typical Mid-Pennsylvanian lycopsid forests. Tree-ferns dominantly grew in aggrading floodbasin settings, and a few of the largest trees show evidence for post-burial regeneration. Being approximately coeval with the late Mid-Pennsylvanian extinction event, which resulted in tree-fern forests rising to dominate tropical lowlands for the first time, the Cranberry Head fossil forests provide insight into community composition and structure during a critical phase of ecosystem reorganization.
Eocene initiation of Ross Sea dextral faulting and implications for East Antarctic neotectonics
Authors: Rossetti Federico , Storti Fabrizio , Busetti Martina , Lisker Frank , Di Vincenzo Gianfranco , Läufer Andreas L. , Rocchi Sergio , Salvini Francesco
Published: December 2005

The Ross Sea region of the East Antarctic plate provides evidence for intraplate tectonic activity in Cenozoic times. Still unresolved are the cause, timing and kinematics of this intraplate tectonism. By integrating and discussing the different (kinematic and temporal) signals of Cenozoic tectonism, intraplate dextral shearing is recognized as the main tectonic regime controlling the structural architecture of the Ross Sea region from the Mid-Eocene (
c
. 40–50 Ma) onward. We speculate that propagation and persistence of this tectonic regime through time constitutes a feasible seismogenetic framework to explain past and current tectonism in the Ross Sea region.
Intrusion-induced uplift and mass wasting of the Palaeogene volcanic landscape of Ardnamurchan, NW Scotland
Authors: Brown David J. , Bell Brian R.
Published: December 2005

Fragmental rocks associated with the exhumed hearths of the Palaeogene volcanoes of NW Scotland have previously been interpreted as classic examples of vent-filling agglomerates of pyroclastic origin. Mapping and logging of these lithologies at the Ardnamurchan Central Complex indicate that they comprise conglomerates of debris flow origin, interbedded with fluvial–lacustrine units, which developed on a dissected landscape during the volcanic and intrusive activity. Clast-matrix analysis allows the palaeo-topography and drainage systems to be inferred, and palynological data are used to develop a palaeogeographical model for the volcanic landscape. A source-region uplift model links the catastrophic mass wasting events to the shallow emplacement of the central complex intrusions.
LESSONS FROM LACTOSE PERMEASE
Authors: Guan Lan , Kaback H. Ronald
Published: December 2005

An X-ray structure of the lactose permease of Escherichia coli (LacY) in an inward-facing conformation has been solved. LacY contains N- and C-terminal domains, each with six transmembrane helices, positioned pseudosymmetrically. Ligand is bound at the apex of a hydrophilic cavity in the approximate middle of the molecule. Residues involved in substrate binding and H+ translocation are aligned parallel to the membrane at the same level and may be exposed to a water-filled cavity in both the inward- and outward-facing conformations, thereby allowing both sugar and H+ release directly into either cavity. These structural features may explain why LacY catalyzes galactoside/H+ symport in both directions utilizing the same residues. A working model for the mechanism is presented that involves alternating access of both the sugar- and H+-binding sites to either side of the membrane.
GENETIC DISORDERS OF PROGRAMMED CELL DEATH IN THE IMMUNE SYSTEM
Authors: Bidère Nicolas , Su Helen C. , Lenardo Michael J.
Published: December 2005

Human genetics offers new possibilities for understanding physiological regulatory mechanisms and disorders of the immune system. Genetic abnormalities of lymphocyte cell death programs have provided insights into mechanisms of receptor biology and principles of immune homeostasis and tolerance. Thus far, there are two major diseases of programmed cell death associated with inherited human mutations: the autoimmune lymphoproliferative syndrome and the caspase-eight deficiency state. We describe the details of their molecular pathogenesis and discuss how these diseases illustrate important concepts in immune regulation and genetics.
LASER PROBING OF SINGLE-AEROSOL DROPLET DYNAMICS
Authors: Reid Jonathan P. , Mitchem Laura
Published: December 2005

▪ Abstract  Aerosols play a critical role in a diverse range of scientific disciplines. To characterize and quantify their role, it is essential that the fundamental details of mass and heat transfer between the aerosol particle and surrounding medium, the properties of multiphase droplets, and the coagulation of aerosol droplets be more fully explored. Elastic and inelastic light scattering can provide information on particle size, composition, morphology, and temperature. In addition, spatial inhomogeneities in composition and temperature can be probed. We review how such techniques can be used to develop an understanding of the chemical and physical dynamics of a single aerosol droplet.
WHAT AFFECTS VOTER TURNOUT?
Authors: Blais André
Published: December 2005

▪ Abstract  Why is turnout higher in some countries and/or in some elections than in others? Why does it increase or decrease over time? To address these questions, I start with the pioneer studies of Powell and Jackman and then review more recent research. This essay seeks to establish which propositions about the causes of variations in turnout are consistently supported by empirical evidence and which ones remain ambiguous. I point out some enigmas and gaps in the field and suggest directions for future research. Most of the research pertains to established democracies, but analyses of nonestablished democracies are also included here.
Intravenous administration of amino acids during anesthesia stimulates muscle protein synthesis and heat accumulation in the body
Authors: Yamaoka Ippei , Doi Masako , Nakayama Mitsuo , Ozeki Akane , Mochizuki Shinji , Sugahara Kunio , Yoshizawa Fumiaki
Published: December 2005

The present study was conducted to determine the contribution of muscle protein synthesis to the prevention of anesthesia-induced hypothermia by intravenous administration of an amino acid (AA) mixture. We examined the changes of intraperitoneal temperature (Tcore) and the rates of protein synthesis ( Ks) and the phosphorylation states of translation initiation regulators and their upstream signaling components in skeletal muscle in conscious (Nor) or propofol-anesthetized (Ane) rats after a 3-h intravenous administration of a balanced AA mixture or saline (Sal). Compared with Sal administration, the AA mixture administration markedly attenuated the decrease in Tcore in rats during anesthesia, whereas Tcore in the Nor-AA group became slightly elevated during treatment. Stimulation of muscle protein synthesis resulting from AA administration was observed in each case, although Ks remained lower in the Ane-AA group than in the Nor-Sal group. AA administration during anesthesia significantly increased insulin concentrations to levels ∼6-fold greater than in the Nor-AA group and enhanced phosphorylation of eukaryotic initiation factor 4E-binding protein-1 (4E-BP1) and ribosomal protein S6 protein kinase relative to all other groups and treatments. The alterations in the Ane-AA group were accompanied by hyperphosphorylation of protein kinase B and the mammalian target of rapamycin (mTOR). These results suggest that administration of an AA mixture during anesthesia stimulates muscle protein synthesis via insulin-mTOR-dependent activation of translation initiation regulators caused by markedly elevated insulin and, thereby, facilitates thermal accumulation in the body.
Physiological and pathophysiological aspects of ceramide
Authors: Gulbins Erich , Li Pin Lan
Published: December 2005

Activation of cells by receptor- and nonreceptor-mediated stimuli not only requires a change in the activity of signaling proteins but also requires a reorganization of the topology of the signalosom in the cell. The cell membrane contains distinct domains, rafts that serve the spatial organization of signaling molecules in the cell. Many receptors or stress stimuli transform rafts by the generation of ceramide. These stimuli activate the acid sphingomyelinase and induce a translocation of this enzyme onto the extracellular leaflet of the cell membrane. Surface acid sphingomyelinase generates ceramide that serves to fuse small rafts and to form large ceramide-enriched membrane platforms. These platforms cluster receptor molecules, recruit intracellular signaling molecules to aggregated receptors, and seem to exclude inhibitory signaling factors. Thus ceramide-enriched membrane platforms do not seem to be part of a specific signaling pathway but may facilitate and amplify the specific signaling elicited by the cognate stimulus. This general function may enable these membrane domains to be critically involved in the induction of apoptosis by death receptors and stress stimuli, bacterial and viral infections of mammalian cells, and the regulation of cardiovascular functions.
Role of fibroblast growth factor-binding protein in the pathogenesis of HIV-associated hemolytic uremic syndrome
Authors: Ray Patricio E. , Tassi Elena , Liu Xue-Hui , Wellstein Anton
Published: December 2005

A characteristic finding of childhood HIV-associated hemolytic uremic syndrome (HIV-HUS) is the presence of endothelial injury and microcystic tubular dilation, leading to a rapid progression of the renal disease. We have previously shown that a secreted fibroblast growth factor-binding protein (FGF-BP) is upregulated in kidneys from children affected with HIV-HUS and HIV nephropathy. Here, we sought to determine the potential role of FGF-BP in the pathogenesis of HIV-HUS. By immunohistochemical and in situ hybridization studies, we observed FGF-BP protein and mRNA upregulation in regenerating renal tubular epithelial cells from kidneys of HIV-Tg26mice with late-stage renal disease, that is, associated with the development of microcystic tubular dilatation and accumulation of FGF-2. Moreover, FGF-BP increased the FGF-2-dependent growth and survival of cultured primary human renal glomerular endothelial cells and enhanced FGF-2-induced MAPK/ERK2 activation, as well as the proliferation of immortalized GM7373 endothelial cells. We propose that HIV-Tg26mice are a clinically relevant model system to study the role of FGF-BP in the pathogenesis of HIV-associated renal diseases. Furthermore, the upregulation of FGF-BP by regenerating renal tubular epithelial cells may provide a mechanism by which the regenerative and angiogenic activity of FGF-2 in renal capillaries can be modulated in children with HIV-HUS and other renal disease.
Vasopressin induces expression of the Cl−/HCO3− exchanger SLC26A7 in kidney medullary collecting ducts of Brattleboro rats
Authors: Petrovic Snezana , Amlal Hassane , Sun Xuming , Karet Fiona , Barone Sharon , Soleimani Manoocher
Published: December 2005

SLC26A7 is a newly identified basolateral Cl−/HCO3− exchanger specific to α-intercalated cells of the outer medullary collecting duct (OMCD). The purpose of the present experiments was to examine the expression of SLC26A7 in kidneys of vasopressin-deficient Brattleboro rats before and after treatment with desamino-Cys1,d-Arg8-vasopressin (dDAVP). Brattleboro rats were treated with dDAVP, a vasopressin analog, for 8 days, and their kidneys were examined for the expression of SLC26A7. The expression of SLC26A7 protein, as examined by immunofluorescence, was undetectable in kidneys of Brattleboro rats. However, treatment with dDAVP induced expression of SLC26A7 protein, restoring it to levels observed in normal rats. These results were verified by Western blot analysis. The mRNA expression of SLC26A7 remained unchanged in response to dDAVP. Immunofluorescent labeling demonstrated abundant levels of anion exchanger type 1 in the OMCD of Brattleboro rats and a mild reduction in response to dDAVP. The abundance of H+-ATPase was not affected by dDAVP. The increased SLC26A7 expression directly correlated with enhanced aquaporin-2 expression, which is proportional to increased interstitial osmolarity in the medulla. In conclusion, vasopressin increases the expression of SLC26A7 protein through posttranscriptional mechanisms in the OMCD. The induction of SLC26A7 by vasopressin in OMCD cells of Brattleboro rats is likely an attempt by cells to regulate their cell volume and maintain HCO3− absorption in a state associated with increased interstitial medullary tonicity.
The Impact of the Canadian Hypertension Education Program on Antihypertensive Prescribing Trends
Authors: Campbell Norman R.C. , Tu Karen , Brant Rollin , Duong-Hua Minh , McAlister Finlay A.
Published: December 2005

Although previous studies have shown that hypertension management has improved in Canada during the past decade, this study was designed to determine whether these changes were temporally related to initiation of the Canadian Hypertension Education Program in 1999. Antihypertensive prescription rates in Ontario were compared using time series analyses before and after 1999 in 2 Ontario cohorts: all hypertensives prescribed therapy (using the Intercontinental Medical Statistics CompuScript Database) and all elderly hypertensives without diabetes prescribed therapy (using linked administrative databases including the Ontario Drug Benefit Database). Between January 1998 and December 2003, &280 million prescriptions for antihypertensive agents were filled in Ontario, and total antihypertensive prescriptions increased by 58% annually; time series analyses confirmed that the prescribing rates for total antihypertensives, thiazide diuretics, β-blockers, and calcium channel blockers increased significantly after 1999, even after adjustment for the temporal trends in the pre-1999 data. In the 166 018 nondiabetic individuals over age 65 who were newly treated for hypertension in Ontario between July 1994 and March 2002, changes in prescription rates for total antihypertensive drugs, angiotensin-converting enzyme inhibitors, β blockers, and calcium channel blockers occurred in directions that were consistent with guideline recommendations and were statistically significantly related to the initiation of the Canadian Hypertension Education Program. The substantial changes in prescription rates for guideline-recommended antihypertensive drug classes in elderly Ontarians without diabetes and the general Ontario population seen in the past decade are temporally related to the initiation of the Canadian Hypertension Education Program.
Out-of-Hemodialysis-Unit Blood Pressure Is a Superior Determinant of Left Ventricular Hypertrophy
Authors: Agarwal Rajiv , Brim Neva J. , Mahenthiran Jothiharan , Andersen Martin J. , Saha Chandan
Published: December 2005

Blood pressures (BPs) obtained in the dialysis unit correlate poorly with ambulatory BP and left-ventricular hypertrophy (LVH). We compared the performance of BP obtained within and outside the dialysis unit as a correlate of LVH. BP was obtained in the dialysis unit using routine and standardized methods and outside the dialysis unit using home and ambulatory BP monitoring in 140 patients (mean age, 56 years; 89 men; 129 blacks; and 59 with diabetes mellitus) on chronic hemodialysis for ≥3 months. Dialysis unit BP recordings were averaged over 2 weeks, and home BP averaged over 1 week. Ambulatory BP monitoring was performed during an interdialytic interval. Echocardiography was performed immediately after dialysis for the assessment of left-ventricular mass. Left ventricular mass/height
2.7
of >51 g/m
2
was taken as evidence of LVH. Test performance of various BPs was compared using receiver operating characteristic curves. Average ambulatory BP was 129.7±21.2/73.6±13.1 mm Hg, home BP was 139.4±21.2/79.0±12.5 mm Hg, standardized predialysis BP was 142.1±21.7/74.9±13.3 mm Hg, postdialysis was 120.9±20.8/69.6±12.5 mm Hg, routine predialysis was 145.6±20.7/79.4±13.1 mm Hg, and postdialysis was 132.0±19.3/72.6±11.1 mm Hg. Left ventricular mass/height
2.7
was 59.1±16.5, and 68% had LV hypertrophy. Diastolic BP measured by any technique was not associated with LVH. Routine and standardized measurements of BP were similarly weak correlates of LVH. Systolic BP outside the dialysis unit was a stronger correlate of LVH compared with dialysis unit BP.
Sympathetic Neural Outflow and Chemoreflex Sensitivity Are Related to Spontaneous Breathing Rate in Normal Men
Authors: Narkiewicz Krzysztof , van de Borne Philippe , Montano Nicola , Hering Dagmara , Kara Tomas , Somers Virend K.
Published: December 2005

Respiration contributes importantly to short-term modulation of sympathetic nerve activity. However, the relationship between spontaneous breathing rate, chemoreflex function, and direct measures of sympathetic traffic in healthy humans has not been studied previously. We tested the hypothesis that muscle sympathetic nerve activity and chemoreflex sensitivity are linked independently to respiratory rate in normal subjects. We studied 69 normal male subjects aged 29.6±8.1 years. Subjects were subdivided according to the tertiles of respiratory rate distributions. Mean respiration rate was 10.6 breaths/min in the first tertile, 14.8 breaths/min in the second tertile, and 18.0 breaths/min in the third tertile. Subjects from the third tertile (faster respiratory rate) had greater sympathetic activity than subjects from the first tertile (slower respiratory rate; 29±3 versus 17±2 bursts/min;
P
<0.001). Stepwise multiple linear regression analysis revealed that only respiratory rate was linked independently to sympathetic activity (
r
=0.42;
P
<0.001). In comparison to subjects with slow respiratory rate, subjects with fast respiratory rate had greater increases in minute ventilation during both hypercapnia (7.3±0.8 versus 3.2±1.0 L/min;
P
=0.005) and hypoxia (5.7±0.8 versus 2.4±0.7 L/min;
P
=0.007). Muscle sympathetic nerve activity and chemoreflex sensitivity are linked to spontaneous respiratory rate in normal humans. Faster respiratory rate is associated with higher levels of sympathetic traffic and potentiated responses to hypoxia and hypercapnia. Spontaneous breathing frequency, central sympathetic outflow, and chemoreflex sensitivity exhibit significant and hitherto unrecognized interactions in the modulation of neural circulatory control.
System y+Arginine Transport and NO Production in Peripheral Blood Mononuclear Cells in Pregnancy and Preeclampsia
Authors: McCord Nicola , Ayuk Paul , McMahon Melanie , Boyd Richard C.A. , Sargent Ian , Redman Christopher
Published: December 2005

Systemic inflammation and oxidative stress are features of normal pregnancy and, in excess, contribute to the pathogenesis of preeclampsia. Inflammatory cell activation stimulates uptake of arginine (the precursor for nitric oxide) by transport system y+, expression of one of its genes (CAT-2) together with inducible nitric oxide synthase, leading to nitric oxide production. We investigated whether these changes occur in peripheral blood mononuclear cells in normal pregnancy and are exaggerated in preeclampsia. Samples from matched trios of nonpregnant, normal pregnant, and preeclamptic women were studied. Arginine transport was characterized, and the expression of inducible nitric oxide synthase and cell-specific nitric oxide production were measured. Arginine uptake by system y+was significantly increased (P<0.001) in peripheral blood mononuclear cells in normal pregnancy but not in preeclampsia. CAT-2 mRNA was not detected in cells from nonpregnant women but was detected in 3 of 10 normal pregnant and 8 of 10 of preeclamptic women (P<0.001). Inducible nitric oxide synthase protein expression was significantly increased in normal pregnant women (P<0.05) but not preeclamptic women. No significant differences in cell-specific nitric oxide production were observed. These changes confirm the predictions for normal pregnancy but not for preeclampsia in which, despite increases in CAT-2 expression, arginine uptake is not additionally increased. This may create a relative deficiency of arginine in PBMCs favoring superoxide and peroxynitrite production and contribute to oxidative and nitrosative stress in preeclampsia.
Metabolomic Identification of Novel Biomarkers of Myocardial Ischemia
Authors: Sabatine Marc S. , Liu Emerson , Morrow David A. , Heller Eric , McCarroll Robert , Wiegand Roger , Berriz Gabriel F. , Roth Frederick P. , Gerszten Robert E.
Published: December 2005

Background—

Recognition of myocardial ischemia is critical both for the diagnosis of coronary artery disease and the selection and evaluation of therapy. Recent advances in proteomic and metabolic profiling technologies may offer the possibility of identifying novel biomarkers and pathways activated in myocardial ischemia.

Methods and Results—

Blood samples were obtained before and after exercise stress testing from 36 patients, 18 of whom demonstrated inducible ischemia (cases) and 18 of whom did not (controls). Plasma was fractionated by liquid chromatography, and profiling of analytes was performed with a high-sensitivity electrospray triple-quadrupole mass spectrometer under selected reaction monitoring conditions. Lactic acid and metabolites involved in skeletal muscle AMP catabolism increased after exercise in both cases and controls. In contrast, there was significant discordant regulation of multiple metabolites that either increased or decreased in cases but remained unchanged in controls. Functional pathway trend analysis with the use of novel software revealed that 6 members of the citric acid pathway were among the 23 most changed metabolites in cases (adjusted
P
=0.04). Furthermore, changes in 6 metabolites, including citric acid, differentiated cases from controls with a high degree of accuracy (
P
<0.0001; cross-validated
c
-statistic=0.83).

Conclusions—

We report the novel application of metabolomics to acute myocardial ischemia, in which we identified novel biomarkers of ischemia, and from pathway trend analysis, coordinate changes in groups of functionally related metabolites.
Democracy and Equality
Authors: Post Robert
Published: December 2005

If democracy is defined as the form of government dedicated to the realization of the values of selfdetermination, democracy bears a complex relationship to equality. Democracy requires equality of democratic agency, which is different from the forms of equality that flow from the values of distributive justice or fairness. Indeed, insofar as the forms of equality demanded by distributive justice are defined by reference to philosophic reason, rather than by reference to democratic self-determination, there is an intrinsic tension between democracy and distributive justice. This tension is reflected in the common conflict between rights and legislative competence. But insofar as violations of the equality required by distributive justice impair democratic legitimacy, democracy requires that these violations be rectified. Changing conceptions of distributive justice may thus fundamentally alter the preconditions of democratic legitimacy.
Vietnam Service, Combat, and Lifetime Educational Attainment
Authors: Lyons Michael J. , Kremen William S. , Franz Carol , Grant Michael D. , Brenner Heather Thompson , Boake Corwin , Eisen Seth
Published: December 2005

Combat experiences early in adulthood may have lifelong ramifications. In the Vietnam Era Twin Study of Aging (VETSA), the authors studied lifetime educational attainment (LEA) in 236 male twins from the Vietnam Era Twin Registry. Twins who served in Vietnam had completed significantly fewer years of education by their 50s. Level of combat exposure was negatively correlated with LEA. To control for variables that might confound the relationship between combat and LEA, the authors compared twin pairs discordant for Vietnam service ( n = 44 pairs); the twins who served in Vietnam had significantly lower LEA than their cotwins. Greater cognitive ability at military induction and older age at induction both predicted higher LEA, but after statistically controlling for these variables, the relationship between combat exposure and LEA remained significant. The VETSA results demonstrate that combat experience and entering military service at a younger age may reduce lifelong educational prospects, even after cognitive ability is controlled.
The Effect of Military Service on Wealth Accumulation
Authors: Fitzgerald Kelly G.
Published: December 2005

This study examines the association between serving active military duty and wealth accumulation. It was expected that those who served active duty would be more likely to accumulate less wealth than nonveterans. Using data from the first wave of the Health and Retirement Study, a sample of 5,800 men was analyzed to determine the relationship between the length of time spent on active military duty and net worth. Multiple regressions suggest that factors commonly associated with wealth accumulation significantly affect net worth. More important, the total number of years served was very significant in that additional years of service decreased net worth. The results were insignificant for respondents who served more than 20 years but suggest that extended military service may positively affect net worth. Overall, the results show that there is an economic disincentive to serve in the military, which may affect the ability of veterans to accumulate wealth and future military recruitment.
Gender-Specific Homicide Offending in Rural Areas
Authors: Lee Matthew R. , Stevenson Ginger D.
Published: December 2005

This analysis departs from prior macro-level homicide research by focusing on genderspecific homicide rates in rural areas, a completely neglected topic. Drawing on the resource deprivation and gender inequality perspectives, the authors analyze genderd is aggregated homicide offending rates in 1,678 rural counties. Negative binomial regression models provide evidence of the following: Gender-specific measures of unemployment and poverty and a measure of female-headed households exhibit no relationship with female homicide offending, whereas all three measures are associated with elevated levels of male homicide offending. Further, measures of both absolute and relative gender inequality have no association with female or male homicide offending in the rural context. Overall, female homicide offending in rural areas is strongly driven by levels of male offending, which are explained by many of the same factors typically cited in the literature on urban crime.
InterferenceAnalyzer: Tools for the analysis and simulation of multi-locus genetic data
Authors: Viswanath Lalitha , Housworth Elizabeth A
Published: December 2005

Background

Good statistical models for analyzing and simulating multilocus recombination data exist but are not accessible to many biologists because their use requires reasonably sophisticated mathematical and computational implementation. While some labs have direct access to statisticians or programmers competent to carry out such analyses, many labs do not. We have created a platform independent application with an easy-to-use graphical user interface that will carry out such analyses including the simulations needed to bootstrap confidence intervals for the parameters of interest. This software should make multi-locus techniques accessible to labs that previously relied on less powerful and potentially statistically confounded single interval or double interval techniques.

Results

We introduce InterferenceAnalyzer, an implementation with a user-friendly graphical interface incorporating previously developed algorithms for the analysis and simulation of multilocus recombination data. We demonstrate the use and features of the program with an example of multilocus tetrad data from the mustard plant, Arabidopsis thaliana, and the yeast, Saccharomyces cerevisiae.

Conclusion

InterferenceAnalyzer provides easy access to the powerful and appropriate statistical tools for the multi-locus analysis of genetic data.
Kalign – an accurate and fast multiple sequence alignment algorithm
Authors: Lassmann Timo , Sonnhammer Erik LL
Published: December 2005

Background

The alignment of multiple protein sequences is a fundamental step in the analysis of biological data. It has traditionally been applied to analyzing protein families for conserved motifs, phylogeny, structural properties, and to improve sensitivity in homology searching. The availability of complete genome sequences has increased the demands on multiple sequence alignment (MSA) programs. Current MSA methods suffer from being either too inaccurate or too computationally expensive to be applied effectively in large-scale comparative genomics.

Results

We developed Kalign, a method employing the Wu-Manber string-matching algorithm, to improve both the accuracy and speed of multiple sequence alignment. We compared the speed and accuracy of Kalign to other popular methods using Balibase, Prefab, and a new large test set. Kalign was as accurate as the best other methods on small alignments, but significantly more accurate when aligning large and distantly related sets of sequences. In our comparisons, Kalign was about 10 times faster than ClustalW and, depending on the alignment size, up to 50 times faster than popular iterative methods.

Conclusion

Kalign is a fast and robust alignment method. It is especially well suited for the increasingly important task of aligning large numbers of sequences.
The role and performance of chest X-ray for the diagnosis of tuberculosis: A cost-effectiveness analysis in Nairobi, Kenya
Authors: van Cleeff MRA , Kivihya-Ndugga LE , Meme H , Odhiambo JA , Klatser PR
Published: December 2005

Background

The objective of this study was to establish 1) the performance of chest X-ray (CXR) in all suspects of tuberculosis (TB), as well as smear-negative TB suspects and 2) to compare the cost-effectiveness of the routine diagnostic pathway using Ziehl-Neelsen (ZN) sputum microscopy followed by CXR if case of negative sputum result (ZN followed by CXR) with an alternative pathway using CXR as a screening tool (CXR followed by ZN).

Methods

From TB suspects attending a chest clinic in Nairobi, Kenya, three sputum specimens were examined for ZN and culture (Lowenstein Jensen). Culture was used as gold standard. From each suspect a CXR was made using a four point scoring system: i: no pathology, ii: pathology not consistent for TB, iii: pathology consistent for TB and iv: pathology highly consistent for TB. The combined score i + ii was labeled as "no TB" and the combined score iii + iv was labeled as "TB". Films were re-read by a reference radiologist. HIV test was performed on those who consented. Laboratory and CXR costs were used to compare for cost-effectiveness.

Results

Of the 1,389 suspects enrolled, for 998 (72%) data on smear, culture and CXR was complete. 714 films were re-read, showing a 89% agreement (kappa value = 0.75 s.e.0.037) for the combined scores "TB" or "no-TB". The sensitivity/specificity of the CXR score "TB" among smear-negative suspects was 80%/67%. Using chest CXR as a screening tool in all suspects, sensitivity/specificity of the score "any pathology" was 92%, respectively 63%. The cost per correctly diagnosed case was for the routine process $8.72, compared to $9.27 using CXR as screening tool. When costs of treatment were included, CXR followed by ZN became more cost-effective.

Conclusion

The diagnostic pathway ZN followed by CXR was more cost-effective as compared to CXR followed by ZN. When cost of treatment was also considered CXR followed by ZN became more cost-effective. The low specificity of chest X-ray remains a subject of concern. Depending whether CXR was performed on all suspects or on smear-negative suspects only, 22%–45% of patients labeled as "TB" had a negative culture. The introduction of a well-defined scoring system, clinical conferences and a system of CXR quality control can contribute to improved diagnostic performance.