bluuebunny/crossref_metadata_2025_split huggingface dataset:
Multifunctional drugs with different CNS targets for neuropsychiatric disorders
Authors: Van der Schyf Cornelis J. , Geldenhuys Werner J. , Youdim Moussa B. H. 
Published: October 2006

AbstractThe multiple disease etiologies that lead to neuropsychiatric disorders, such as Parkinson's and Alzheimer's disease, amyotrophic lateral sclerosis, Huntington disease, schizophrenia, depressive illness and stroke, offer significant challenges to drug discovery efforts aimed at preventing or even reversing the progression of these disorders. Transcriptomic tools and proteomic profiling have clearly indicated that such diseases are multifactorial in origin. Further, they are thought to be initiated by a cascade of molecular events that involve several neurotransmitter systems. In response to this complexity, a new paradigm has recently emerged that challenges the widely held assumption that ‘silver bullet’ agents are superior to ‘dirty drugs’ in therapeutic approaches aimed at the prevention or treatment of neuropsychiatric diseases. A similar pattern of drug development has occurred in strategies for the treatment of cancer, AIDS and cardiovascular diseases. In this review, we offer an overview of therapeutic strategies and novel investigative drugs discovered or developed in our own and other laboratories, that address multiple CNS etiological targets associated with an array of neuropsychiatric disorders.
Mass‐independent fractionation of sulfur isotopes in sulfides from the pre‐3770 Ma Isua Supracrustal Belt, West Greenland
Authors: PAPINEAU D. , MOJZSIS S. J. 
Published: October 2006

ABSTRACTRedox chemistry of the coupled atmosphere–hydrosphere system has coevolved with the biosphere, from global anoxia in the Archean to an oxygenated Proterozoic surface environment. However, to trace these changes to the very beginning of the rock record presents special challenges. All known Eoarchean (c. 3850–3600 Ma) volcanosedimentary successions (i.e. supracrustal rocks) are restricted to high‐grade gneissic terranes that seldom preserve original sedimentary structures and lack primary organic biomarkers. Although complicated by metamorphic overprinting, sulfur isotopes from Archean supracrustal rocks have the potential to preserve signatures of both atmospheric chemistry and metabolic fractionation from the original sediments. We present a synthesis of multiple sulfur isotope measurements (32S, 33S and 34S) performed on sulfides from amphibolite facies banded iron‐formations (BIFs) and ferruginous garnet‐biotite (metapelitic) schists from the pre‐3770 Ma Isua Supracrustal Belt (ISB) in West Greenland. Because these data come from some of the oldest rocks of interpretable marine sedimentary origin, they provide the opportunity to (i) explore for possible biosignatures of sulfur metabolisms in early life; (ii) assess changes in atmospheric redox chemistry from ∼3.8 Ga; and (iii) lay the groundwork to elucidate sulfur biogeochemical cycles on the early Earth. We find that sulfur isotope results from Isua do not unambiguously indicate microbially induced sulfur isotopic fractionation at that time. A significantly expanded data set of Δ33S analyses for Isua dictates that the atmosphere was devoid of free oxygen at time of deposition and also shows that the effects of post‐depositional metamorphic remobilization and/or dilution can be traced in mass‐independently fractionated sulfur isotopes.
Surfactant as a carrier: influence of immunosuppressive agents on surfactant activity
Authors: Gommers D. , Haitsma J. J. , Lachmann B. 
Published: October 2006

SummaryIntroduction  It has been proposed that exogenous pulmonary surfactant can be used as a drug delivery system for immunosuppressive agents to the alveolar compartment of the lung while reducing the risk of systemic toxicity. Before using this combination, however, alterations in activity of both substances should be examined. Therefore, this study investigated whether the activity of a natural derived surfactant preparation is changed after it is mixed with cyclosporine A (CsA) or rapamycin (RPM).Methods  A surfactant suspension was mixed with CsA or RPM and minimal surface tension of these mixtures was measured in vitro. Surfactant activity was evaluated in vivo by its capacity to restore gas exchange in an established model of surfactant deficiency in rats. CsA–surfactant, RPM–surfactant or surfactant alone was instilled intratracheally and blood gases were measured under standardized ventilatory conditions.Results  Minimal surface tension of surfactant–CsA was comparable with that of surfactant alone, whereas minimal surface tension of the surfactant–RPM mixture was increased. In vivo partial arterial oxygen pressure levels increased immediately to prelavage values after instillation of CsA–surfactant, RPM–surfactant and surfactant only and were comparable during the entire study period.Conclusion  The activity of a naturally derived surfactant was affected when mixed with RPM but not when mixed with CsA at the used concentrations.
Geographic variation in diapause induction under constant and changing conditions in Helicoverpa armigera
Authors: Shimizu Ken , Fujisaki Kenji 
Published: October 2006

AbstractVariation in the incidence of diapause in local populations of Helicoverpa armigera (Hübner) and Helicoverpa assulta (Guenée) (Lepidoptera: Noctuidae) was examined in relation to changes in photoperiod and/or temperature during the larval period. Temperate zone populations of H. assulta, a native species in temperate Japan, showed a high incidence of diapause induction when only the photoperiod was decreased during the larval period, even at favorable temperatures. This photoperiod‐dependent response may allow H. assulta to foresee the beginning of autumn well in advance in the temperate zone, where temperature conditions are severe. In contrast, temperate zone populations of H. armigera, an invasive and polyphagous species mainly distributed in the subtropics, showed a high incidence of diapause only when both photoperiod and temperature decreased, whereas subtropical populations showed a very low incidence of diapause under the same conditions. Furthermore, both temperate zone and subtropical populations of H. armigera enter diapause under constant low temperatures at short‐day photoperiod. Thus, there is geographic variation in sensitivity to diapause‐inducing stimuli (changes in photoperiod and temperature) in H. armigera. This variation may be a part of the climatic adaptation achieved by H. armigera in Japan.
Metabolic phenotyping of mouse mutants in the German Mouse Clinic
Authors: ELVERT Ralf , EHRHARDT Nicole , TAUBE Martin , KLINGENSPOR Martin , GAILUS‐DURNER Valerie , FUCHS Helmut , DE ANGELIS Martin Hrabe , BLANQUET Veronique , HELDMAER Gerhard 
Published: October 2006

AbstractThe German Mouse Clinic was established as a phenotyping center to provide the scientific community with systematic standardized phenotyping of mouse models from various genetic backgrounds. We found metabolic phenotypes in nine out of 20 mutant lines screened in a primary screen. Based on these findings, the mutants were analyzed in secondary and tertiary screens. Mice of a sample mutant line, isolated from the ENU‐screen at the National Research Center for Environment and Health in Munich, were found to have lower body weight, consume less food, but have higher ratios of metabolized energy per unit body weight compared with their wild‐type littermates. Basal metabolic rate and heat production were simultaneously increased by 16–18%, whereas body fat content was reduced by 11–16%. The combination of various parameters of energy consumption, expenditure and energy storage illustrate the metabolic demands of the sample mutant mouse line and demonstrate the utility of the powerful phenotyping tool used at the German Mouse Clinic.
The Relaxase of the
Rhizobium etli
Symbiotic Plasmid Shows
nic
Site
cis
-Acting Preference
Authors: Pérez-Mendoza Daniel , Lucas María , Muñoz Socorro , Herrera-Cervera José A. , Olivares José , de la Cruz Fernando , Sanjuán Juan 
Published: October 2006

ABSTRACT

Genetic and biochemical characterization of TraA, the relaxase of symbiotic plasmid pRetCFN42d from
Rhizobium etli
, is described. After purifying the relaxase domain (N265TraA), we demonstrated
nic
binding and cleavage activity in vitro and thus characterized for the first time the nick site (
nic
) of a plasmid in the family
Rhizobiaceae
. We studied the range of N265TraA relaxase specificity in vitro by testing different oligonucleotides in binding and nicking assays. In addition, the ability of pRetCFN42d to mobilize different
Rhizobiaceae
plasmid origins of transfer (
oriT
) was examined. Data obtained with these approaches allowed us to establish functional and phylogenetic relationships between different plasmids of this family. Our results suggest novel characteristics of the
R. etli
pSym relaxase for previously described conjugative systems, with emphasis on the
oriT cis
-acting preference of this enzyme and its possible biological relevance.
Serine/Threonine Protein Kinase SpkA in
Synechocystis
sp. Strain PCC 6803 Is a Regulator of Expression of Three Putative
pilA
Operons, Formation of Thick Pili, and Cell Motility
Authors: Panichkin Vladimir B. , Arakawa-Kobayashi Satoko , Kanaseki Toku , Suzuki Iwane , Los Dmitry A. , Shestakov Sergey V. , Murata Norio 
Published: October 2006

ABSTRACT

Previous studies showed that a Ser/Thr protein kinase, SpkA, in
Synechocystis
sp. strain PCC 6803 is involved in cell motility. The present study, in which DNA microarray analysis and electron microscopy were used, demonstrated that SpkA regulates the expression of putative
pilA9-pilA10-pilA11
-slr2018,
pilA5-pilA6
, and
pilA1-pilA2
operons and is essential for the formation of thick pili.
Novel Role of
mfd
: Effects on Stationary-Phase Mutagenesis in
Bacillus subtilis
Authors: Ross Christian , Pybus Christine , Pedraza-Reyes Mario , Sung Huang-Mo , Yasbin Ronald E. , Robleto Eduardo 
Published: October 2006

ABSTRACT

Previously, using a chromosomal reversion assay system, we established that an adaptive mutagenic process occurs in nongrowing
Bacillus subtilis
cells under stress, and we demonstrated that multiple mechanisms are involved in generating these mutations (41, 43). In an attempt to delineate how these mutations are generated, we began an investigation into whether or not transcription and transcription-associated proteins influence adaptive mutagenesis. In
B. subtilis
, the Mfd protein (transcription repair coupling factor) facilitates removal of RNA polymerase stalled at transcriptional blockages and recruitment of repair proteins to DNA lesions on the transcribed strand. Here we demonstrate that the loss of Mfd has a depressive effect on stationary-phase mutagenesis. An association between Mfd mutagenesis and aspects of transcription is discussed.
Distal Colorectal Cancers with Microsatellite Instability (MSI) Display Distinct Gene Expression Profiles that Are Different from Proximal MSI Cancers
Authors: Watanabe Toshiaki , Kobunai Takashi , Toda Etsuko , Yamamoto Yoko , Kanazawa Takamitsu , Kazama Yoshihiro , Tanaka Junichiro , Tanaka Toshiaki , Konishi Tsuyosi , Okayama Yoshihiro , Sugimoto Yoshikazu , Oka Toshinori , Sasaki Shin , Muto Tetsuichiro , Nagawa Hirokazu 
Published: October 2006

Abstract
Promoter methylation of the mismatch repair gene plays a key role in sporadic microsatellite instability (MSI) colorectal cancers. However, promoter methylation often occurs in proximal colon cancers, and molecular phenotypes underlying MSI cancers in distal colon have not been fully clarified. Our goal was to clarify the difference between MSI and microsatellite stability (MSS) cancers and, furthermore, to determine distinct characteristics of proximal and distal MSI cancers. By DNA microarray analysis of 84 cancers (33 MSI and 51 MSS), we identified discriminating genes (177 probe sets), which predicted MSI status with a high accuracy rate (97.6%). These genes were related to phenotypic characteristics of MSI cancers. Next, we identified 24 probe sets that were differentially expressed in proximal and distal MSI cancers. These genes included promoter methylation-mediated genes, whose expression was significantly down-regulated in proximal MSI cancers. Among discriminating genes between MSI and MSS, nine methylation-mediated genes showed down-regulation in MSI cancers. Of these, 7 (77.8%) showed down-regulation in proximal MSI cancers. Furthermore, methylation-specific PCR confirmed that frequency of hMLH1 promoter methylation was significantly higher in proximal MSI cancers (P = 0.0317). These results suggested that there is a difference between proximal and distal MSI cancers in methylation-mediated influence on gene silencing. In conclusion, using DNA microarray, we could distinguish MSI and MSS cancers. We also showed distinct characteristics of proximal and distal MSI cancers. The inactivation form of hMLH, per se, differed between proximal and distal MSI cancers. These results suggested that distal MSI cancers constitute a distinct subgroup of sporadic MSI cancers. (Cancer Res 2006; 66(20): 9804-8)
Individualization in Europe and America: Connecting Religious and Moral Values
Authors: Cochrane Christopher , Nevitte Neil 
Published: October 2006

AbstractAfter reviewing the major variations in how individualization is interpreted and explained, this article turns to the World Values Survey (WVS) data to empirically investigate one central aspect of individualization, namely, the connection between religiosity and moral values. That analysis demonstrates, first, that rates of decline in levels of religiosity in most advanced industrial states have been quite modest. The rate of change in moral outlooks, by contrast, has been much more striking. Those two core findings, we argue, draw attention to the question of what explains these cross-national and cross-time variations. The remainder of the article empirically explores a variety of plausible explanations. The results of that analysis reveal not only significant variations between European and North American publics, but also that associational behavior plays a significant role in gearing the dynamics of individualization.
Restricting Discretion: Judicial Review of Diplomatic Protection
Authors: Vermeer-Künzli Annemarieke 
Published: October 2006

AbstractIn the last 30 years, individuals have increasingly filed complaints against their national governments for failure to exercise diplomatic protection on their behalf, in particular in cases of serious violations of international human rights law. Despite the fact that diplomatic protection has traditionally been regarded as a discretionary right of states, the national courts have invariably decided to enter into the merits of the case and to review the exercise of diplomatic protection by the executive. Initially, a draft article on this subject was not accepted by the International Law Commission in the Draft Articles on first reading, but an encouraging provision was included in the Draft Articles adopted on second reading. The development discussed in this article shows support for an obligation to exercise diplomatic protection in case of serious violations of human rights law.
Numerical Simulation of Dust Lifting within Dust Devils—Simulation of an Intense Vortex
Authors: Gu Zhaolin , Zhao Yongzhi , Li Yun , Yu Yongzhang , Feng Xiao 
Published: October 2006

Abstract
Based on an advanced dust devil–scale large-eddy simulation (LES) model, the atmosphere flow of a modeled dust devil in a quasi–steady state was first simulated to illustrate the characteristics of the gas phase field in the mature stage, including the prediction of the lower pressure and higher temperature in the vortex core. The dust-lifting physics is examined in two aspects. Through the experimental data analysis, it is verified again that the horizontal swirling wind can only make solid particles saltate along the ground surface. Based on a Lagrangian reference frame, the tracks of dust grains with different density (material) and diameter are calculated to show the effect of dust particles entrained by the vertical swirling wind field. The movement of solid particles depends on the interactions between the aloft dust particles and the airflow field of dust devils, in which the drag and the centrifugal force component on the horizontal plane are the key force components. There is the trend of the fine dust grains rising along the inner helical tracks while the large dust grains are lifting along the outer helical tracks and then descending beyond the corner region, resulting in the impact between different-sized dust grains in the swirling atmospheric flow. This trend will make the dust stratification, developing a top small-sized grain domain and a bottom large-sized grain domain in dust devils.
A Gray-Radiation Aquaplanet Moist GCM. Part I: Static Stability and Eddy Scale
Authors: Frierson Dargan M. W. , Held Isaac M. , Zurita-Gotor Pablo 
Published: October 2006

Abstract
In this paper, a simplified moist general circulation model is developed and used to study changes in the atmospheric general circulation as the water vapor content of the atmosphere is altered. The key elements of the model physics are gray radiative transfer, in which water vapor and other constituents have no effect on radiative fluxes, a simple diffusive boundary layer with prognostic depth, and a mixed layer aquaplanet surface boundary condition. This GCM can be integrated stably without a convection parameterization, with large-scale condensation only, and this study focuses on this simplest version of the model. These simplifications provide a useful framework in which to focus on the interplay between latent heat release and large-scale dynamics. In this paper, the authors study the role of moisture in determining the tropospheric static stability and midlatitude eddy scale. In a companion paper, the effects of moisture on energy transports by baroclinic eddies are discussed.
The authors vary a parameter in the Clausius–Clapeyron relation to control the amount of water in the atmosphere, and consider circulations ranging from the dry limit to 10 times a control value. The typical length scale of midlatitude eddies is found to be remarkably insensitive to the amount of moisture in the atmosphere in this model. The Rhines scale evaluated at the latitude of the maximum eddy kinetic energy fits the model results for the eddy scale well. Moist convection is important in determining the extratropical lapse rate, and the dry stability is significantly increased with increased moisture content.
Nonlocal Treatment of the Buoyancy-Shear-Driven Boundary Layer
Authors: Ferrero E. , Colonna N. 
Published: October 2006

Abstract
A successful description of a convective boundary layer requires that the model employed takes into account the nonlocal nature of turbulent convection. In this paper new third-order moments (TOMs) are presented and tested. Numerical solutions are obtained using mean flow components and second-order moments as input. The problem of the turbulent damping of the TOMs is considered. The terms in the dynamic equations responsible for the unphysical growth of the TOMs are parameterized, taking into account their dependence on the integral length scale vertical profile. The calculated profiles are presented and tested against large-eddy simulation data and aircraft measurements. In both cases the results compare favorably.
Transport of the essential nutrient isoleucine in human erythrocytes infected with the malaria parasite Plasmodium falciparum
Authors: Martin Rowena E. , Kirk Kiaran 
Published: October 2006

AbstractThe intraerythrocytic malaria parasite derives much of its requirement for amino acids from the digestion of the hemoglobin of its host cell. However, one amino acid, isoleucine, is absent from adult human hemoglobin and must therefore be obtained from the extracellular medium. In this study we have characterized the mechanisms involved in the uptake of isoleucine by the intraerythrocytic parasite. Under physiologic conditions the rate of transport of isoleucine into human erythrocytes infected with mature trophozoite-stage Plasmodium falciparum parasites is increased to approximately 5-fold that in uninfected cells, with the increased flux being via the new permeability pathways (NPPs) induced by the parasite in the host cell membrane. Transport via the NPPs ensures that protein synthesis is not rate limited by the flux of isoleucine across the erythrocyte membrane. On entering the infected erythrocyte, isoleucine is taken up into the parasite via a saturable, ATP-, Na+-, and H+-independent system which has the capacity to mediate the influx of isoleucine in exchange for leucine (liberated from hemoglobin). The accumulation of radiolabeled isoleucine within the parasite is mediated by a second (high-affinity, ATP-dependent) mechanism, perhaps involving metabolism and/or the concentration of isoleucine within an intracellular organelle.
Pivotal Advance: α-Galactosylceramide induces protection against lipopolysaccharide-induced shock
Authors: Sireci Guido , La Manna Marco P , Di Sano Caterina , Di Liberto Diana , Porcelli Steven A , Kronenberg Mitch , Dieli Francesco , Salerno Alfredo 
Published: October 2006

Abstractα−galactosylceramide, a natural killer T cell ligand, and its synthetic homolog, KRN7000, consistently influence IFN-γ and TNF-α release, both mediators of LPS-induced shock. To modify the course of endotoxin shock, we injected KRN7000 at different time points of experimental systemic Shwartzman reaction. Mice treated with KRN7000 survived when it was injected within 2 h before and after LPS challenge. Mice survival was associated with low levels of T helper 1 (Th1) cytokines, such as IFN-γ and TNF-α. By contrast, protection from endotoxin shock was associated with an increase of T helper 2 (Th2) cytokines, like IL-4 and IL-10. A role of Th2 cytokines in counteracting LPS-induced shock was supported by experiments in which the protection against Shwartzman reaction by KRN7000 was abrogated by in vivo coadministration of anti-Th2 cytokines antibodies. In addition, cytofluorimetric analysis showed that surviving animals have higher percentages of NKT-IL-10-positive cells and lower percentages of NKT-IFN-γ and macrophages/TNF-α-stained cells than nonprotected mice. Taken together, our data demonstrate that KRN7000 treatment given at times near LPS challenge is protective for endotoxin shock inhibiting IFN-γ and TNF-α release. Moreover, KRN7000-mediated protection occurs through an increased production of IL-4 and IL-10, which are mainly secreted by NKT cells. Since IFN-γ release by NKT requires a longer TCR stimulation than that required for Th2 cytokines production, we demonstrate that timing of KRN7000 in vivo exposure affect the pattern of cytokines expression protecting animals by endotoxin shock.