bluuebunny/crossref_metadata_2025_split huggingface dataset:
Asiatic acid derivatives enhance cognitive performance partly by improving acetylcholine synthesis
Authors: Kim So Ra , Koo Kyung Ah , Lee Mi Kyeong , Park Hyeung-geun , Jew Sang-sup , Cha Kyung-hoe , Kim Young Choong 
Published: September 2004

Abstract
Thirty-six semi-synthesized derivatives of asiatic acid were examined to determine if they had cognitive-enhancing activity in a passive avoidance test. Among the compounds tested, AS-2, AS-2–9–006 and AS-9–006 significantly alleviated scopolamine-induced memory impairment at doses of 1 and 10 mg kg−1. Furthermore, AS-2 and AS-2–9–006 (1 mg kg−1 administered four times daily) enhanced cognitive performance as determined in a water maze test. These three asiatic acid derivatives did not show any significant effect on the learning process in active avoidance tests. AS-2, AS-2–9–006 and AS-9–006 enhanced cholineacetyltransferase activity in a cholinergic neuroblastoma cell line, S-20Y, in-vitro. Therefore, AS-2, AS-2–9–006 and AS-9–006 may have therapeutic value in alleviating certain memory impairment observed in dementia.
Degradation of berenil (diminazene aceturate) in acidic aqueous solution
Authors: Campbell Michael , Prankerd Richard J , Davie Ashley S , Charman William N 
Published: September 2004

Abstract
The trypanocide berenil was assessed for chemical stability over the pH range 1–8 at 37°C and 0.2 m ionic strength. It was found to be sufficiently unstable under acid conditions that its therapeutic efficacy is most likely severely compromised when administered orally. At pH 3, the half-life was 35 min, decreasing to 1.5 min at pH 1.75. Reaction rate constants were corrected for the effects of buffer catalysis and were found to range from 2.00 min−1 at pH 1 to 6.1 × 10−6 min−1 at pH 8. The pH-rate profile displayed a region (pH 1–4) where specific acid catalysis was dominant, followed by a transitional region (pH 5–7), and finally a region (pH &gt; 7) where uncatalysed degradation was most important. It is recommended that berenil be enteric coated for formulations to be used in treating Third World parasitic diseases.
Pluronic block copolymers and Pluronic poly(acrylic acid) microgels in oral delivery of megestrol acetate
Authors: Alakhov Valery , Pietrzynski Grzegorz , Patel Kishore , Kabanov Alexander , Bromberg Lev , Hatton T Alan 
Published: September 2004

Abstract
Several Pluronic-based formulations were studied in-vitro and in a rat model with respect to the release and bioavailability of megestrol acetate (MA) after oral administration. It was demonstrated that an aqueous, micellar formulation comprising a mixture of a hydrophobic (L61) and a hydrophilic (F127) Pluronic copolymer, significantly enhanced the bioavailability of MA administered orally at relatively low doses (1–7 mg kg−1). Pluronic-based microgels (spherical gel particles of sub-millimetre size) were introduced as MA vehicles. The microgels comprised a cross-linked network of poly(acrylic acid) onto which the Pluronic chains were covalently attached. Microgels of Pluronic L92 and poly(acrylic acid) fabricated into tablet dosage forms exhibited dramatically lowered MA initial burst release. The MA release was pH-dependent owing to the pH sensitivity of the microgel swelling, with the drug retained by the microgel at pH 1.8 and released slowly at pH 6.8. In the rat model, a significant increase in MA bioavailability was observed when the microgel-formulated MA was administered orally at a high dose of 10 mg kg−1, owing to the enhanced retention of the microgel. The study of the microgel passage through the gastrointestinal tract demonstrated the microgel retention characteristic of a very high molecular weight polymer and the absence of any systemic absorption of the polymer.
Decrease in oral bioavailability of ciclosporin by intravenous pulse of methylprednisolone succinate in rats
Authors: Konishi Hiroki , Sumi Masaki , Shibata Nobuhito , Takada Kanji , Minouchi Tokuzo , Yamaji Akira 
Published: September 2004

Abstract
We examined the effects of high-dose methylprednisolone on the bioavailability of orally administered ciclosporin in rats. To emulate the clinical protocol of methylprednisolone pulse therapy, methylprednisolone sodium succinate (MPS), a prodrug of methylprednisolone, was intravenously administered as repeated doses (66.3 mg kg−1) for 3 days. The area under the blood ciclosporin concentration versus time curve after oral administration was significantly reduced by 60% by pulse treatment with MPS. Based on our previous finding that the total body clearance of ciclosporin was reduced by about 20% by the same methylprednisolone pulse protocol, the extent of reduction in the oral bioavailability of ciclosporin was estimated to be approximately 50%, indicating a drug interaction between high-dose methylprednisolone and orally administered ciclosporin, which affected the absorption process. In rats treated with MPS, an in-situ efflux experiment using rhodamine-123 demonstrated that the reverse transport function of P-glycoprotein (P-gp) in the small intestine was significantly enhanced, although there was no significant increase in the intestinal microsomal activity of triazolam α- and 4-hydroxylation, metabolic probes for CYP3A. In addition, a significant decrease was observed in the amount of secreted bile acids serving as an enhancer of gastrointestinal absorption of ciclosporin in MPS treatment. To directly estimate the absorptive capacity, an in-situ absorption test was conducted using a closed-loop of small intestine in control and MPS-treated rats. Intestinal absorption of ciclosporin was significantly decreased, not only in the absence of bile flow but also by treatment with MPS, which well reflected the change in the in-vivo pharmacokinetic behaviour of ciclosporin after methylprednisolone pulsing. These results demonstrate that bioavailability of ciclosporin is markedly reduced by MPS pulse treatment, and the mechanism of this interaction was confirmed to involve enhancement of small-intestinal P-gp function and decrease in bile secretion.
Protective effects of the Chinese prescription Hachimi-jio-gan against diabetic oxidative stress
Authors: Kim Hyun Young , Yokozawa Takako , Cho Eun Ju , Yamabe Noriko 
Published: September 2004

Abstract
We used rats with streptozotocin (STZ)-induced diabetes to investigate the effects of Hachimi-jiogan on diabetic oxidative stress. Oral administration of Hachimi-jio-gan, at a dose of 50, 100 or 200 mg kg−1 (body weight) daily, for 10 days to rats with STZ-induced diabetes resulted in significant dose-dependent decreases in serum levels of glucose and glycosylated protein, implying that Hachimi-jio-gan improves the abnormal glucose metabolism that leads to oxidative stress. Hachimi-jio-gan also showed a tendency to reduce the urine volume and significantly reduced the elevated urinary protein level. Moreover, rats with STZ-induced diabetes had high serum levels of superoxide and nitrite/nitrate. However, the administration of Hachimi-jio-gan dose-dependently reduced the overproduction of radicals associated with diabetes, suggesting the role of Hachimi-jio-gan as a radical scavenger that could protect against diabetic oxidative stress. Furthermore, thiobarbituric acid-reactive substance levels in serum and hepatic and renal mitochondria were dose-dependently lower in the Hachimi-jio-gan-treated groups than in the control diabetic group, which implies that Hachimi-jio-gan would alleviate the oxidative stress associated with diabetes through the inhibition of lipid peroxidation. These results indicate that Hachimi-jio-gan is a potential therapeutic agent that will reduce the damage caused by oxidative stress involved in diabetes.
Deconstructing ‘globalisation’ in Ireland
Authors: Smith Nicola Jo-Anne 
Published: September 2004

English
The Irish Republic has been widely hailed as a ‘showpiece of globalisation’. This article argues that although Ireland has experienced considerable change in recent years, there is little evidence to suggest that its economy has indeed been ‘globalised’. Yet the discursive construction of globalisation may in itself play an independent causal role in shaping political outcomes. The article thus also explores the role of ideas about globalisation in shaping Irish policy change.
The new regulatory state and relational capacity
Authors: Jayasuriya Kanishka 
Published: September 2004

English
Globalisation has transformed the internal architecture of the state, leading to the emergence of a new form of regulatory state that operates through mechanisms of metagovernance – that is, the governance of governance. This has important implications for various models of policy capacity. Conventional accounts of policy capacity embody an attribute model of capacity that seeks to identify a set of transformative powers over policy and structure. In contrast, the new regulatory state requires that capacity be understood as a relational term that structures various sites of governance and links dispersed regulatory resources and agents.
Characterization of endothelin-1 and nitric oxide generating systems in corpus luteum-derived endothelial cells
Authors: Klipper Eyal , Gilboa Tamar , Levy Nitzan , Kisliouk Tatiana , Spanel-Borowski Katharina , Meidan Rina 
Published: September 2004

Endothelium-derived endothelin-1 (ET-1) and nitric oxide (NO) are pivotal regulators of corpus luteum (CL) function. To have a better insight into their synthesis and action, members of the ET system (ET-1, ET converting enzyme (ECE-1) isoforms a–d, ETAand ETBreceptors) along with NO synthase (NOS) isoforms – endothelial (e)NOS and inducible (i)NOS – were quantified in CL-derived endothelial cells (CLEC). The expression of these genes in microvascular CLEC, obtained by lectin-coated magnetic beads, was compared with cells removed from the luteal microenvironment and maintained in culture for different durations, and with endothelial cells (EC) derived from a large blood vessel (i.e. bovine aortic endothelial cells, BAEC). The profile of gene expression in the different EC types was determined by quantitative real-time PCR. Freshly isolated EC from mid-cycle CL exhibited high ET-1 receptor expression (both ETAand ETB), low ET-1 synthesizing ability (both prepro (pp) ET-1 and ECE-1), but elevated iNOS – the high throughput NOS isoform. The distinct phenotype of CLEC was lost soon after an overnight culture. ETAand ETBreceptor levels declined, ppET-1 levels increased while iNOS was reduced. These changes were extenuated during long-term culture of CLEC. The general pattern of gene expression in BAEC and long-term cultured CLEC was similar yet some differences, reminiscent of freshly isolated CLEC, remained: ECE-1c, ETBreceptor and NOS isoforms were expressed differently in BAEC as compared with lines of CLEC.This study suggests that the luteal microenvironment is necessary to sustain the selective phenotype of its resident endothelial cells. The inverse relationship between ppET-1 and iNOS observed in freshly isolated CLEC and in cultured cells is physiologically significant and suggests that ET-1 and NO may modulate the production of each other.
Heterochromatin Spreading at Yeast Telomeres Occurs in M Phase
Authors: Martins-Taylor Kristen , Dula Mary Lou , Holmes Scott G 
Published: September 2004

Abstract
Heterochromatin regulation of gene expression exhibits epigenetic inheritance, in which some feature of the structure is retained and can reseed formation in new cells. To understand the cell-cycle events that influence heterochromatin assembly and maintenance in budding yeast, we have conducted two types of experiments. First we have examined the kinetics of heterochromatin spreading at telomeres. We have constructed a strain in which the efficient silencing of a telomere-linked URA3 gene depends on the inducible expression of the Sir3 silencing factor. Prior studies determined that S-phase passage was required for the establishment of silencing at the HM loci in yeast. We find that establishment of silencing in our strain occurs at a point coincident with mitosis and does not require S-phase passage. In addition, we find that passage through mitosis is sufficient to establish silencing at the HML locus in a strain bearing a conditional allele of SIR3. Finally, we have also assessed the stability of yeast heterochromatin in the absence of the cis-acting elements required for its establishment. We show that silencing is stable through S phase in the absence of silencers and therefore possesses the ability to self-propagate through DNA replication. However, silencing is lost in the absence of silencers during progression through M phase. These experiments point to crucial events in mitosis influencing the assembly and persistence of heterochromatin.
Population Genetics of Polymorphism and Divergence for Diploid Selection Models With Arbitrary Dominance
Authors: Williamson Scott , Fledel-Alon Adi , Bustamante Carlos D 
Published: September 2004

Abstract
We develop a Poisson random-field model of polymorphism and divergence that allows arbitrary dominance relations in a diploid context. This model provides a maximum-likelihood framework for estimating both selection and dominance parameters of new mutations using information on the frequency spectrum of sequence polymorphisms. This is the first DNA sequence-based estimator of the dominance parameter. Our model also leads to a likelihood-ratio test for distinguishing nongenic from genic selection; simulations indicate that this test is quite powerful when a large number of segregating sites are available. We also use simulations to explore the bias in selection parameter estimates caused by unacknowledged dominance relations. When inference is based on the frequency spectrum of polymorphisms, genic selection estimates of the selection parameter can be very strongly biased even for minor deviations from the genic selection model. Surprisingly, however, when inference is based on polymorphism and divergence (McDonald-Kreitman) data, genic selection estimates of the selection parameter are nearly unbiased, even for completely dominant or recessive mutations. Further, we find that weak overdominant selection can increase, rather than decrease, the substitution rate relative to levels of polymorphism. This nonintuitive result has major implications for the interpretation of several popular tests of neutrality.
Duplicative and Conservative Transpositions of Larval serum protein 1 Genes in the Genus DrosophilaSequence data from this article have been deposited with the EMBL/GenBank Data Libraries under accession nos. AY561258 and AY561259.
Authors: González Josefa , Casals Ferran , Ruiz Alfredo 
Published: September 2004

AbstractInterspecific comparative molecular analyses of transposed genes and their flanking regions can help to elucidate the time, direction, and mechanism of gene transposition. In the Drosophila melanogaster genome, three Larval serum protein 1 (Lsp1) genes (α, β and γ) are present and each of them is located on a different chromosome, suggesting multiple transposition events. We have characterized the molecular organization of Lsp1 genes in D. buzzatii, a species of the Drosophila subgenus and in D. pseudoobscura, a species of the Sophophora subgenus. Our results show that only two Lsp1 genes (β and γ) exist in these two species. The same chromosomal localization and genomic organization, different from that of D. melanogaster, is found in both species for the Lsp1β and Lsp1γ genes. Overall, at least two duplicative and two conservative transpositions are necessary to explain the present chromosomal distribution of Lsp1 genes in the three Drosophila species. Clear evidence for implication of snRNA genes in the transposition of Lsp1β in Drosophila has been found. We suggest that an ectopic exchange between highly similar snRNA sequences was responsible for the transposition of this gene. We have also identified the putative cis-acting regulatory regions of these genes, which seemingly transposed along with the coding sequences.
A Screen for Genes That Interact With the Drosophila Pair-Rule Segmentation Gene fushi tarazu
Authors: Kankel Mark W , Duncan Dianne M , Duncan Ian 
Published: September 2004

Abstract
The pair-rule gene fushi tarazu (ftz) of Drosophila is expressed at the blastoderm stage in seven stripes that serve to define the even-numbered parasegments. ftz encodes a DNA-binding homeodomain protein and is known to regulate genes of the segment polarity, homeotic, and pair-rule classes. Despite intensive analysis in a number of laboratories, how ftz is regulated and how it controls its targets are still poorly understood. To help understand these processes, we conducted a screen to identify dominant mutations that enhance the lethality of a ftz temperature-sensitive mutant. Twenty-six enhancers were isolated, which define 21 genes. All but one of the mutations recovered show a maternal effect in their interaction with ftz. Three of the enhancers proved to be alleles of the known ftz protein cofactor gene ftz-f1, demonstrating the efficacy of the screen. Four enhancers are alleles of Atrophin (Atro), the Drosophila homolog of the human gene responsible for the neurodegenerative disease dentatorubral-pallidoluysian atrophy. Embryos from Atro mutant germ-line mothers lack the even-numbered (ftz-dependent) engrailed stripes and show strong ftz-like segmentation defects. These defects likely result from a reduction in Even-skipped (Eve) repression ability, as Atro has been shown to function as a corepressor for Eve. In this study, we present evidence that Atro is also a member of the trithorax group (trxG) of Hox gene regulators. Atro appears to be particularly closely related in function to the trxG gene osa, which encodes a component of the brahma chromatin remodeling complex. One additional gene was identified that causes pair-rule segmentation defects in embryos from homozygous mutant germ-line mothers. The single allele of this gene, called bek, also causes nuclear abnormalities similar to those caused by alleles of the Trithorax-like gene, which encodes the GAGA factor.
The Genetic Basis of Male Fertility in Relation to Haplodiploid Reproduction in Leptopilina clavipes (Hymenoptera: Figitidae)
Authors: Pannebakker Bart A , Beukeboom Leo W , van Alphen Jacques J M , Brakefield Paul M , Zwaan Bas J 
Published: September 2004

AbstractTraits under relaxed selection are expected to become reduced or disappear completely, a process called vestigialization. In parthenogenetic populations, traits historically involved in sexual reproduction are no longer under selection and potentially subject to such reduction. In Leptopilina clavipes, thelytokous (parthenogenetic) populations are infected by Wolbachia bacteria. Arrhenotokous populations do not harbor Wolbachia. When antibiotics are applied to infected females, they are cured from their infection and males arise. Such males are capable of producing offspring with uninfected females, but with lower fertilization success than sexual males. This can be attributed to the lack of selection on male fertility in thelytokous lines. In this study we used this variation in L. clavipes male fertility to determine the genetic basis of this trait. Males from cured thelytokous populations were crossed to females from uninfected populations. Using AFLP markers, a genetic linkage map was generated, consisting of five linkage groups and spanning a total distance of 219.9 cM. A single QTL of large effect (explaining 46.5% of the phenotypic variance) was identified for male fertility, which we call male fertility factor (mff). We discuss possible mechanisms underlying the effect of mff, as well as mechanisms involved in vestigialization of traits involved in sexual reproduction.
Does Crossover Interference Count in Saccharomyces cerevisiae?
Authors: Stahl Franklin W , Foss Henriette M , Young Lisa S , Borts Rhona H , Abdullah M F F , Copenhaver Gregory P 
Published: September 2004

Abstract
We previously proposed a “counting model” for meiotic crossover interference, in which double-strand breaks occur independently and a fixed number of noncrossovers occur between neighboring crossovers. Whereas in some organisms (group I) this simple model alone describes the crossover distribution, in other organisms (group II) an additional assumption—that some crossovers lack interference—improves the fit. Other differences exist between the groups: Group II needs double-strand breaks and some repair functions to achieve synapsis, while repair in group I generally occurs after synapsis is achieved; group II, but not group I, has recombination proteins Dmc1, Mnd1, and Hop2. Here we report experiments in msh4 mutants that are designed to test predictions of the revised model in a group II organism. Further, we interpret these experiments, the above-mentioned differences between group I and II meiosis, and other data to yield the following proposal: Group II organisms use the repair of leptotene breaks to promote synapsis by generating double-Holliday-junction intermediates that lock homologs together (pairing pathway). The possible crossover or noncrossover resolution products of these structures lack interference. In contrast, for both group I and group II, repair during pachytene (disjunction pathway) is associated with interference and generates only two resolution types, whose structures suggest that the Holliday junctions of the repair intermediates are unligated. A crossover arises when such an intermediate is stabilized by a protein that prevents its default resolution to a noncrossover. The protein-binding pattern required for interference depends on clustering of sites that have received, or are normally about to receive, meiotic double-strand breaks.
Exo1 and Rad24 Differentially Regulate Generation of ssDNA at Telomeres of Saccharomyces cerevisiae cdc13-1 Mutants
Authors: Zubko Mikhajlo K , Guillard Sandrine , Lydall David 
Published: September 2004

Abstract
Cell cycle arrest in response to DNA damage depends upon coordinated interactions between DNA repair and checkpoint pathways. Here we examine the role of DNA repair and checkpoint genes in responding to unprotected telomeres in budding yeast cdc13-1 mutants. We show that Exo1 is unique among the repair genes tested because like Rad9 and Rad24 checkpoint proteins, Exo1 inhibits the growth of cdc13-1 mutants at the semipermissive temperatures. In contrast Mre11, Rad50, Xrs2, and Rad27 contribute to the vitality of cdc13-1 strains grown at permissive temperatures, while Din7, Msh2, Nuc1, Rad2, Rad52, and Yen1 show no effect. Exo1 is not required for cell cycle arrest of cdc13-1 mutants at 36° but is required to maintain arrest. Exo1 affects but is not essential for the production of ssDNA in subtelomeric Y′ repeats of cdc13-1 mutants. However, Exo1 is critical for generating ssDNA in subtelomeric X repeats and internal single-copy sequences. Surprisingly, and in contrast to Rad24, Exo1 is not essential to generate ssDNA in X or single-copy sequences in cdc13-1 rad9Δ mutants. We conclude that Rad24 and Exo1 regulate nucleases with different properties at uncapped telomeres and propose a model to explain our findings.
Functional Analysis of Drosophila melanogaster Gene Regulatory Sequences by Transgene Coplacement
Authors: Parsch John 
Published: September 2004

Abstract
The function of putative regulatory sequences identified by comparative genomics can be elucidated only through experimentation. Here the effectiveness of using heterologous gene constructs and transgene coplacement to characterize regulatory sequence function is demonstrated. This method shows that a sequence in the Adh 3′-untranslated region negatively regulates expression, independent of gene or chromosomal context.