bluuebunny/crossref_metadata_2025_split huggingface dataset:
Preclinical Evaluation of 1H-Benzylindole Derivatives as Novel Human Immunodeficiency Virus Integrase Strand Transfer Inhibitors
Authors: Hombrouck Anneleen , Van Remoortel Barbara , Michiels Martine , Noppe Wim , Christ Frauke , Eneroth Anders , Sahlberg Britt Louise , Benkestock Kurt , Vrang Lotta , Johansson Nils Gunnar , Barreca Maria Letizia , De Luca Laura , Ferro Stefania , Chimirri Alba , Debyser Zeger , Witvrouw Myriam 
Published: June 2008

ABSTRACT

We have identified 1H-benzylindole analogues as a novel series of human immunodeficiency virus (HIV) integrase inhibitors with antiretroviral activities against different strains of HIV type 1 (HIV-1), HIV-2, and simian immunodeficiency virus strain MAC
251
[SIV(MAC
251
)]. Molecular modeling and structure-activity relationship-based optimization resulted in the identification of CHI/1043 as the most potent congener. CHI/1043 inhibited the replication of HIV-1(III
B
) in MT-4 cells at a 50% effective concentration (EC
50
) of 0.60 μM, 70-fold below its cytotoxic concentration. Equal activities against HIV-1(NL4.3), HIV-2(ROD), HIV-2(EHO), and SIV(MAC
251
) were observed. CHI/1043 was equally active against virus strains resistant against inhibitors of reverse transcriptase or protease. Replication of both X4 and R5 strains in peripheral blood mononuclear cells was sensitive to the inhibitory effect of CHI/1043 (EC
50
, 0.30 to 0.38 μM). CHI/1043 inhibited integrase strand transfer activity in oligonucleotide-based enzymatic assays at low micromolar concentrations. Time-of-addition experiments confirmed CHI/1043 to interfere with the viral replication cycle at the time of retroviral integration. Quantitative
Alu
PCR corroborated that the anti-HIV activity is based upon the inhibition of proviral DNA integration. An HIV-1 strain selected for 70 passages in the presence of CHI/1043 was evaluated genotypically and phenotypically. The mutations T66I and Q146K were present in integrase. Cross-resistance to other integrase strand transfer inhibitors, such as L-708,906, the naphthyridine analogue L-870,810, and the clinical drugs GS/9137 and MK-0518, was observed. In adsorption, distribution, metabolism, excretion, and toxicity studies, antiviral activity was strongly reduced by protein binding, and metabolization in human liver microsomes was observed. Transport studies with Caco cells suggest a low oral bioavailability.
Staphylococcus aureus
Cell Wall Stress Stimulon Gene
-lacZ
Fusion Strains: Potential for Use in Screening for Cell Wall-Active Antimicrobials
Authors: Steidl Rebecca , Pearson Stacy , Stephenson Robert E. , Ledala Nagender , Sitthisak Sutthirat , Wilkinson Brian J. , Jayaswal Radheshyam K. 
Published: June 2008

ABSTRACT

lacZ
fusion strains were constructed using the promoters of five cell wall stress stimulon genes:
pbp2
,
tcaA
,
vraSR
,
sgtB
, and
lytR
. All fusion strains were induced only in the presence of cell wall-active antibiotics, suggesting the potential of these strains for use in high-throughput screening for new cell wall-active agents.
Identification of Mutations Related to Streptomycin Resistance in Clinical Isolates of
Mycobacterium tuberculosis
and Possible Involvement of Efflux Mechanism
Authors: Spies Fernanda S. , Almeida da Silva Pedro E. , Ribeiro Marta O. , Rossetti Maria Lucia , Zaha Arnaldo 
Published: June 2008

ABSTRACT

The MIC for streptomycin in the presence of efflux pump (EP) inhibitors and the sequencing of
rpsL
,
rrs
, and
gidB
genes provided evidence for the possible participation of EP in low-level streptomycin (STR) resistance of some isolates without mutations. Mutation in the
gidB
gene and an EP could act synergistically to confer low STR resistance.
Specific Roles of the
iroBCDEN
Genes in Virulence of an Avian Pathogenic
Escherichia coli
O78 Strain and in Production of Salmochelins
Authors: Caza Mélissa , Lépine François , Milot Sylvain , Dozois Charles M. 
Published: June 2008

ABSTRACT

Avian pathogenic
Escherichia coli
(APEC) strains are a subset of extraintestinal pathogenic
E. coli
(ExPEC) strains associated with respiratory infections and septicemia in poultry. The
iroBCDEN
genes encode the salmochelin siderophore system present in
Salmonella enterica
and some ExPEC strains. Roles of the
iro
genes for virulence in chickens and production of salmochelins were assessed by introducing plasmids carrying different combinations of
iro
genes into an attenuated salmochelin- and aerobactin-negative mutant of O78 strain χ7122. Complementation with the
iroBCDEN
genes resulted in a regaining of virulence, whereas the absence of
iroC
,
iroDE
, or
iroN
abrogated restoration of virulence. The
iroE
gene was not required for virulence, since introduction of
iroBCDN
restored the capacity to cause lesions and colonize extraintestinal tissues. Prevalence studies indicated that
iro
sequences were associated with virulent APEC strains. Liquid chromatography-mass spectrometry analysis of supernatants of APEC χ7122 and the complemented mutants indicated that (i) for χ7122, salmochelins comprised 14 to 27% of the siderophores present in iron-limited medium or infected tissues; (ii) complementation of the mutant with the
iro
locus increased levels of glucosylated dimers (S1 and S5) and monomer (SX) compared to APEC strain χ7122; (iii) the
iroDE
genes were important for generation of S1, S5, and SX; (iv)
iroC
was required for export of salmochelin trimers and dimers; and (v)
iroB
was required for generation of salmochelins. Overall, efficient glucosylation (IroB), transport (IroC and IroN), and processing (IroD and IroE) of salmochelins are required for APEC virulence, although IroE appears to serve an ancillary role.
An Interleukin-1β (IL-1β) Single-Nucleotide Polymorphism at Position 3954 and Red Complex Periodontopathogens Independently and Additively Modulate the Levels of IL-1β in Diseased Periodontal Tissues
Authors: Ferreira Samuel B. , Trombone Ana Paula F. , Repeke Carlos E. , Cardoso Cristina R. , Martins Walter , Santos Carlos F. , Trevilatto Paula Cristina , Ávila-Campos Mario J. , Campanelli Ana Paula , Silva João S. , Garlet Gustavo P. 
Published: June 2008

ABSTRACTInflammatory cytokines such as interleukin-1β (IL-1β) are involved in the pathogenesis of periodontal diseases. A high individual variation in the levels of IL-1β mRNA has been verified, which is possibly determined by genetic polymorphisms and/or by the presence of periodontopathogens such asPorphyromonas gingivalis, Tannerella forsythia, Treponema denticola, andAggregatibacter actinomycetemcomitans. In this study, we investigated the role of an IL-1β promoter single-nucleotide polymorphism at position 3954 [IL-1β(3954) SNP] and the presence of the periodontopathogens in the determination of the IL-1β levels in the periodontal tissues of nonsmoking chronic periodontitis (CP) patients (n= 117) and control (C) subjects (n= 175) and the possible correlations with the clinical parameters of the disease. IL-1β(3954) SNP was investigated by restriction fragment length polymorphism, while the IL-1β levels and the presence of the periodontopathogens were determined by real-time PCR. Similar frequencies of IL-1β(3954) SNP were found in the C and CP groups, in spite of a trend toward a higher incidence of T alleles in the CP group. The IL-1β(3954) SNP CT and TT genotypes, as well asP. gingivalis, T. forsythia, andT. denticola, were associated with higher IL-1β levels and with higher values of the clinical parameters of disease severity. Concomitant analyses demonstrate that IL-1β(3954) and the red complex periodontopathogens were found to independently and additively modulate the levels of IL-1β in periodontal tissues. Similarly, the concurrent presence of both factors was associated with increased scores of disease severity. IL-1β(3954) genotypes and red complex periodontopathogens, individually and additively, modulate the levels of IL-1β in the diseased tissues of nonsmoking CP patients and, consequently, are potentially involved in the determination of the disease outcome.
Sortase A Utilizes an Ancillary Protein Anchor for Efficient Cell Wall Anchoring of Pili in
Streptococcus agalactiae
Authors: Nobbs Angela H. , Rosini Roberto , Rinaudo C. Daniela , Maione Domenico , Grandi Guido , Telford John L. 
Published: June 2008

ABSTRACT

Pili are putative virulence factors and promising vaccine candidates in
Streptococcus agalactiae
(group B
Streptococcus
[GBS]) infection, a leading cause of neonatal sepsis and meningitis. The genes necessary for pilus synthesis and assembly are clustered in pilus islands (PI). Each gene encodes three structural subunits (a backbone and two ancillary proteins) bearing a C-terminal LPXTG motif and two subfamily C sortases (SrtC) involved in covalent polymerization of the subunits. GBS strains also possess the conserved “housekeeping” sortase A (SrtA), but its role in pilus assembly is unclear. To address this issue, pilus expression and cell wall anchoring were analyzed in
srtA
deletion mutants. Loss of SrtA did not affect pilus polymerization. However, pilus expression on the cell surface was reduced, and pili accumulated in the culture supernatant. Furthermore, cell-associated pili could be readily released by detergent treatment, indicating that SrtA is involved in covalent anchoring of pili to the cell wall. When each of the genes comprising PI-2a was systematically deleted, only the absence of ancillary subunit GBS150 or the SrtC required for incorporation of GBS150 into pili mimicked the
srtA
mutant phenotype. Thus, from these data a model for GBS pilus assembly can be proposed in which PI sortases are responsible for polymerization of the pilus structure, while SrtA is required to covalently attach it to the cell wall, utilizing ancillary pilus subunit GBS150 as the anchor protein.
Characteristics and analysis of simple sequence repeats in the cotton genome based on a linkage map constructed from a BC1population betweenGossypium hirsutumandG. barbadense
Authors: Zhang Yanxin , Lin Zhongxu , Xia Qizhong , Zhang Mingju , Zhang Xianlong 
Published: June 2008

In the past decade, several molecular maps of cotton have been constructed using diverse DNA molecular markers and mapping populations. In this study, an interspecific linkage map of allotetraploid cotton was developed using a BC1population ((Gossypium hirsutum × G. barbadense) × G. hirsutum). This map was genome-wide and was based entirely on simple sequence repeat (SSR) markers. Forty-four linkage groups were assigned to 26 chromosomes, with 917 loci spanning 5452.2 cM of the genome. The average distance between loci was 5.9 cM, providing uniform coverage of the A subgenome and D subgenome. Characteristics of this map were analyzed in detail, including the distributions of genomic SSRs, expressed sequence tag (EST)-SSRs, and distorted markers. Furthermore, the relationships between motif characteristics (size, type, length) and the level of polymorphism in EST-SSRs were also surveyed. The results showed that tetranucleotide and dinucleotide repeats had similar levels of polymorphism, and ACAT, AC, and ACT repeats had the highest polymorphism rates. Loci with lengths of 27 bp, 33 bp, and 24 bp were more likely to be polymorphic. This work will provide information to assist in designing future EST-SSRs.
Pion fluctuation and its multiplicity dependence in ultrarelativistic nuclear collisions
Authors: Ghosh D , Deb A , Dutta S 
Published: June 2008

This paper studies the multiplicity dependence of the fluctuation pattern of pions produced for 16O–AgBr interactions at 60 A GeV and 32S–AgBr interactions at 200 A GeV. We divided the data for the pions produced into four sets depending on the number of shower tracks (ns). We investigated the fluctuation pattern of emitted pions corresponding to different sets in both η (pseudorapidity) and ϕ (azimuthal angle) space. The multiplicity dependence was studied with respect to parameters αq, Dq, multifractal specific heat c, and effective fluctuation strength αeff. The study clearly indicates that the fluctuation pattern depends on multiplicity both in pseudorapidity and azimuthal angle space for 16O initiated interactions. However, for 32S initiated interactions, no multiplicity dependence is evidenced by the data in azimuthal angle space. For both, the multiplicity dependence is not very strong and significant only at large average multiplicity. Multiplicity dependence was further studied in a small window around the central pseudorapidity, and we found that multiplicity dependence is more prominent in the central region. The multiplicity dependence of αeff is more pronounced in the case of 32S–AgBr interactions than in case of 16O–AgBr interactions. PACS Nos.: 25.75–q, 24.60 Ky
Habitat Defense in Southeast Asian Cities
Authors: Aldrich Brian C. 
Published: June 2008

AbstractUsing interviews with public officials and activists as well as research reports available in Southeast Asia, this research compares the level of organization, mobilization and collective action among neolocal urban groups threatened with removal and relocation for large infrastructure projects. The results show that habitat defense is extensive in Bangkok, Jakarta and Manila, but minor or non-existent in Singapore, Hong Kong and Kuala Lumpur. A model of collective action is nested in an ecological model to explain differences in level of habitat defense among the six Southeast Asian cities.
The Political Role of the Indonesian Military: Past, Present and Future
Authors: Said Salim 
Published: June 2008

AbstractThis paper attempts to briefly examine the political role of the Indonesian military from its inception to its dominant position in Indonesian politics today. It also attempts to discuss whether or not it would continue to play the same role in the future. The paper will be divided into three sections: the political role of the military during the revolution, the increased political involvement of the military, conflicting interpretations of the military role and the possibility of future change.
Locating the Ottomans Among Early Modern Empires
Authors: Aksan Virginia H. 
Published: June 2008

AbstractThis paper describes the evolution of Ottoman military and defensive strategies in the Balkans from 1600 to 1800. It argues that three major imperial crises, engendered by sustained warfare, forced a transition from a standing army to state commissioned militias. To do so, it sites the Ottoman imperial context in a discussion of multiethnic eastern European empires, comparing Ottoman options and limitations with those of the Habsburgs and the Romanovs for the same period. The geopolitics of Danubian and Black Sea frontier territories, and the relationship between imperial center and native elites serve as two points of comparison, emphasizing the interplay between sovereignty, religious affiliation, and assimilation. By the end of the eighteenth century, Ottoman contraction and the movement of large numbers of Muslim refugees from surrendered territories, meant the increased nomadization of central Ottoman lands, and the almost total reliance on undisciplined, volunteer militias as a fighting force, whose acculturation to "Ottomanism" was never desired nor attempted by the ruling elite.
Crossing the Borders: Ireland and the Irish Between England and America
Authors: Hadfield Andrew 
Published: June 2008

AbstractHistorians of early modern Ireland have often been rather too monolithic in their readings of representations of Ireland and the Irish. Many commentators now insist that Ireland has to be viewed in terms of British or European developments. Using examples from a selection of writers—Luke Gernon, Sir Henry Sidney, Sir William Herbert, John Derricke, Barnaby Rich, Sir John Davies—this article argues that Ireland was invariably represented through the use of overlapping, often competing, discourses of savagery and domestic political concerns. In themselves, such discourses can be further sub-divided into various empirical and theoretical modes of writing. Moreover, identical representations were often produced or read in different ways so that the significance of context and register has to be taken into account when examining the evidence available.
Useful To Have, But Difficult To Govern. Inns and Taverns in Early Modern Bern and Vaud
Authors: Kümin Beat 
Published: June 2008

AbstractThis essay examines the significance of inns and taverns in the early modern period. Drawing above all on a series of registers from the French and German lands of the Swiss Republic of Bern, the discussion is presented in two parts. A first section investigates structural aspects such as ownership, clientele, and the remarkably multifunctional character of these establishments. The second part illustrates the continuing growth in provision during the Ancien Régime and the limited impact of government regulation. It is argued that inns and taverns became the most prominent social centres in early modern local communities and that popular demand for their services prevailed over sustained campaigns to restrict numbers and discipline patrons.
Invented Identities: Credulity in the Age of Prophecy and Exploration
Authors: Eliav-Feldon Miriam 
Published: June 2008

AbstractThe sixteenth century was a golden age for impostors and pretenders of many kinds. In addition to the pre-modem lack of means for establishing a person's identity, other contributing factors for the success of impostors were the inability to distinguish between fact and fiction in the flood of reports about newly-discovered lands, the desperate desire of European monarchs to believe in the existence of potential allies against Islam and the eschatological mood bred by the Age of Fear. This article attempts to gauge early modem gullibility by examining the attitudes towards David Reuveni, a self-proclaimed prince from a land of the lost tribes of Israel, who was accepted almost without reservations by Pope, kings and learned cardinals in the 1520s.
The Context of War and Violence in Sixteenth-Century English Society
Authors: Trim David J.B. 
Published: June 2008

AbstractThe Elizabethan epoch has long been regarded as a period in which England, isolated from the rest of Europe, fell behind the Continental powers during an era of "military revolution." More recently, England's sixteenth-century military history has attracted a growing number of scholars, but their conclusions vary widely and seem impossible to integrate. Yet recent analyses have generally been too narrowly focussed on events in Elizabethan England. This article (based on a synthesis of secondary studies, including social and cultural as well as military histories, but supported by evidence from the most important printed primary sources), attempts to put the military history of Tudor England in the setting, firstly of both earlier and later developments in England itself; and secondly, of the wider, contemporaneous experience of warfare in Europe as a whole. An understanding of the context of warfare can provide a better basis for future research into an issue with significant wider implications for early modern historiography.
Challenge To Orthodoxy: Beliefs and Values of the Eternal Mother Sects in Sixteenth-and Seventeenth-Century China
Authors: Shek Richard 
Published: June 2008

AbstractUsing the framework of orthodoxy versus heterodoxy, this paper attempts to establish the following points : (1) An orthodoxy existed in China since the middle of the second century before the common era and lasted until the turn of the present century. (2) This orthodoxy was not articulated by a religious authority, but rather by a political authority. (3) The content of this orthodoxy, socio-political-ethical in emphasis, was defined not by narrow sectarian doctrines but by a compromise consensus among all the major religious traditions in China. (4) Challenge to this orthodoxy was long-lasting and variegated in nature, but at the turn of the sixteenth century crystalized into a potent tradition revolving around a central matriarchal deity and a strong millenarian and eschatological vision. (5) This heterodox tradition, though similarly socio-ethical in content, was by definition also politically subversive and occasionally erupted into anti-dynastic rebellions.
Religion in Contemporary East African Art
Authors: Agthe Johanna 
Published: June 2008

AbstractThis article describes three aspects of religious art in East Africa: firstly it examines the artists' personal attitude to and motivation by the Christian religion; secondly, it looks at Christian and Bible subjects in their paintings; and lastly it considers traditional religion and the newer independent churches as motifs. It draws on interviews with artists, their works in the collection of the Frankfurt Museum für Völkerkunde and a recent unpublished diploma study by Alois Krammer. 1
The Taming of the Prophet Harris
Authors: Shank David A. 
Published: June 2008

AbstractWe have looked at illustrations from a process going from a culture gap in inter-personal contacts, to rapidly scrawled notes—sometimes in a French transcription of heard English, edited in a filled-out synthesis in French, then translated and edited in English, then re-edited and published as a 'full account.' At every stage of the process, one may observe mutations, governed no doubt in large part by the major preoccupation of legitimation of the Wesleyan mission, in all good faith. And it produced the dominant interpretation of the Prophet Harris. The reconstructed message did greatly profit Methodist developments, even though many Harrists could not accept the Wesleyan claim to Harris's authorization of their mission. More important, the Methodists did not stand up as his spokesperson for 'Ethiopian' ways of conjugality ; on the contrary, they used his legitimation to sanction a monogamous discipline. An inherent contradiction was present in that a ministry which they could accept but not fully approve, was used to validate their own. But even more, the Wesleyan Mission clearly did not become a spokesperson for Harris's warnings to the colonial authorities, nor did they wish to seek legitimate authorization for Harris's return ministry in the French colony.37 The consequences of these differences were to have all kinds of implications for the future relationships between Methodists and the Harrists, for whom even today the name and reputation of the white 'Pasteur Benoit' have become ignominious. But in the process, important information was also recorded to permit us to enter into a better understanding of the phenomenal prophet on his own terms, and recognizing—in his own language—that 'God moves in mysterious ways... and uses the foolish things in the world to confound the wise.'38
Skenosis - The Tabernacling of the Word
Authors: Pobee John S. 
Published: June 2008

AbstractThe need for translating the good news of Jesus Christ into a real up-to-date world is recognized by all and sundry. A whole range of terms have been used to designate the need: Africanisation, Localisation, Accomodation, Adaptation, Incarnation, Inculturation, Indigenisation, Aggiornamento. The author, for diverse reasons, offers yet another term Skēnōsis which comes out John 1:14. The term has the merit of being very biblical and emphasizing the dynamic relation and creative tension between the eternal non-negotiable word and the contingent realities of life. Further it underlines the temporary nature of the construct which means skēnōsis must be an on-going process of renewal. The article outlines five major elements of the landscape of the temporal reality of Africa which skēnōsis must engage. Alongside those is set the Word of God which is always received as an interpreted entity, and which is a part of the tradition of the living church. And precisely for that reason there is need for each skēnōsis to engage and be engaged by other attempts in the church universal for mutal correction and affirmation. Some attention is paid to the structures of skēnōsis. The author, however, refuses to do blue-prints particularly because of the diversity in Africa and of Church polity. His interest is only to indicate paths to be explored by each time and place and that in an on-going process.