bluuebunny/crossref_metadata_2025_split huggingface dataset:
Pyrazolopyrimidinediones Are Selective Agents for
Helicobacter pylori
That Suppress Growth through Inhibition of Glutamate Racemase (MurI)
Authors: de Jonge B. L. M. , Kutschke A. , Uria-Nickelsen M. , Kamp H. D. , Mills S. D. 
Published: May 2009

ABSTRACT

Pyrazolopyrimidinediones are a novel series of compounds that inhibit growth of
Helicobacter pylori
specifically. Using a variety of methods, advanced analogues were shown to suppress the growth of
H. pylori
through the inhibition of glutamate racemase, an essential enzyme in peptidoglycan biosynthesis. The high degree of selectivity of the series for
H. pylori
makes these compounds attractive candidates for novel
H. pylori
-selective therapy.
Effect of Rifampin, a Potent Inducer of Drug-Metabolizing Enzymes, on the Pharmacokinetics of Raltegravir
Authors: Wenning Larissa A. , Hanley William D. , Brainard Diana M. , Petry Amelia S. , Ghosh Kalyan , Jin Bo , Mangin Eric , Marbury Thomas C. , Berg Jolene K. , Chodakewitz Jeffrey A. , Stone Julie A. , Gottesdiener Keith M. , Wagner John A. , Iwamoto Marian 
Published: May 2009

ABSTRACT

Raltegravir is a human immunodeficiency virus type 1 integrase strand transfer inhibitor that is metabolized by glucuronidation via UGT1A1 and may be affected by inducers of UGT1A1, such as rifampin (rifampicin). Two pharmacokinetic studies were performed in healthy subjects: study 1 examined the effect of administration of 600-mg rifampin once daily on the pharmacokinetics of a single dose of 400-mg raltegravir, and study 2 examined the effect of 600-mg rifampin once daily on the pharmacokinetics of 800-mg raltegravir twice daily compared to 400-mg raltegravir twice daily without rifampin. Raltegravir coadministered with rifampin resulted in lower plasma raltegravir concentrations: in study 1, the geometric mean ratios (GMRs) and 90% confidence intervals (90% CIs) for the plasma raltegravir concentration determined 12 h postdose (
C
12
), area under the concentration-time curve from 0 h to ∞ (AUC
0-∞
), and maximum concentration of drug in plasma (
C
max
) (400-mg raltegravir plus rifampin/400-mg raltegravir) were 0.39 (0.30, 0.51), 0.60 (0.39, 0.91), and 0.62 (0.37, 1.04), respectively. In study 2, the GMRs and 90% CIs for raltegravir
C
12
, AUC
0-12
, and
C
max
(800-mg raltegravir plus rifampin/400-mg raltegravir) were 0.47 (0.36, 0.61), 1.27 (0.94, 1.71), and 1.62 (1.12, 2.33), respectively. Doubling the raltegravir dose to 800 mg when coadministered with rifampin therefore compensates for the effect of rifampin on raltegravir exposure (AUC
0-12
) but does not overcome the effect of rifampin on raltegravir trough concentrations (
C
12
). Coadministration of rifampin and raltegravir is not contraindicated; however, caution should be used, since raltegravir trough concentrations in the presence of rifampin are likely to be at the lower limit of clinical experience.
Influence of the Cytochrome P450 2B6 Genotype on Population Pharmacokinetics of Efavirenz in Human Immunodeficiency Virus Patients
Authors: Cabrera Salvador E. , Santos Dolores , Valverde María P. , Domínguez-Gil Alfonso , González Francisco , Luna Guillermo , García María J. 
Published: May 2009

ABSTRACTA population pharmacokinetic model for efavirenz has been developed from therapeutic drug monitoring data in human immunodeficiency virus (HIV)-positive patients by using a nonlinear mixed-effect model. The efavirenz plasma concentrations (n= 375) of 131 patients were analyzed using high-performance liquid chromatography with UV detection. Pharmacokinetic parameters were estimated according to a one-compartment model. The effects of sex, age, total body weight, height, body mass index, and HIV treatment were analyzed. In a subgroup of 32 patients, genetic polymorphisms of the cytochrome P450 2B6 gene (CYP2B6),CYP3A4, andMDR1were also investigated. Efavirenz oral clearance and the apparent volume of distribution were 9.50 liters/h and 311 liters, respectively. The model included only the effect ofCYP2B6polymorphisms on efavirenz clearance; this covariate reduced the intersubject variability of clearance by about 27%. Patients showing G/T and T/TCYP2B6polymorphisms exhibited efavirenz clearances that were about 50% and 75% lower than those observed in the patients without these polymorphisms (G/G). Accordingly, to obtain EFV steady-state concentrations within the therapeutic range (1 to 4 mg/liter), it would be advisable to implement a gradual reduction in dose to 400 or 200 mg/day for patients that are intermediate or poor metabolizers, respectively. However, the remaining interindividual variability observed in the pharmacokinetic parameters of the model highlights the need for dose individualization to avoid inadequate exposure to efavirenz and suggests that these recommended doses be used with caution and confirmed by therapeutic drug monitoring and clinical efficacy. The population model can be implemented in pharmacokinetic clinical software for dosage optimization by using the Bayesian approach.
Secretion of GOB Metallo-β-Lactamase in
Escherichia coli
Depends Strictly on the Cooperation between the Cytoplasmic DnaK Chaperone System and the Sec Machinery: Completion of Folding and Zn(II) Ion Acquisition Occur in the Bacterial Periplasm
Authors: Morán-Barrio Jorgelina , Limansky Adriana S. , Viale Alejandro M. 
Published: May 2009

ABSTRACT

Metallo-β-lactamases (MβLs) are zinc-dependent enzymes produced by many clinically relevant gram-negative pathogens that can hydrolyze most β-lactam antibiotics. MβLs are synthesized in the bacterial cytoplasm as precursors and are secreted into the periplasm. Here, we report that the biogenesis process of the recently characterized MβL GOB-18 demands cooperation between a main chaperone system of the bacterial cytoplasm, DnaK, and the Sec secretion machinery. Using the expression of the complete
gob-18
gene from the gram-negative opportunistic pathogen
Elizabethkingia meningoseptica
in
Escherichia coli
as a model system, we found that the precursor of this metalloenzyme is secreted by the Sec pathway and reduces cell susceptibility to different β-lactam antibiotics. Moreover, acting with different J proteins such as cytoplasmic DnaJ and membrane-associated DjlA as cochaperones, DnaK plays an essential role in the cytoplasmic transit of the GOB-18 precursor to the Sec translocon. Our studies also revealed a less relevant role, that of assisting in GOB-18 secretion, for trigger factor, while no significant functions were found for other main cytoplasmic chaperones such as SecB or GroEL/ES. The overall findings indicate that the biogenesis of GOB-18 involves cytoplasmic interaction of the precursor protein mainly with DnaK, secretion by the Sec system, and final folding and incorporation of Zn(II) ions into the bacterial periplasm.
Lipopolysaccharide-Trap-Fc, a Multifunctional Agent To Battle Gram-Negative Bacteria
Authors: Groß Philipp , Brandl Katharina , Dierkes Christine , Schölmerich Jürgen , Salzberger Bernd , Glück Thomas , Falk Werner 
Published: May 2009

ABSTRACTThe family of Toll-like receptors (TLRs) plays a pivotal role in host defense against pathogens. However, overstimulation of these receptors may lead to uncontrolled general inflammation and eventually to systemic organ dysfunction or failure. With the intent to control overwhelming inflammation during gram-negative bacterial sepsis, we constructed soluble fusion proteins of the lipopolysaccharide (LPS)-receptor complex to modulate TLR signaling in multiple ways. The extracellular domain of mouse TLR4 and mouse myeloid differentiation factor 2 (MD-2) fusions (LPS-Trap) were linked to human immunoglobulin G Fc domains (LPS-Trap-Fc). In addition to the ability to bind LPS or gram-negative bacteria and to inhibit interleukin-6 secretion of monocytic cells after LPS treatment, LPS-Trap-Fc was able to opsonize fluorescentEscherichia coliparticles. This led to enhancement of phagocytosis by monocytic cells which was strictly dependent on the presence of the Fc region. Moreover, only LPS-Trap-Fc- and not LPS-Trap-coated bacteria were sensitized to complement killing. Therefore, LPS-Trap-Fc not only neutralizes LPS but also, after binding to bacteria, enhances phagocytosis and complement-mediated killing and could thus act as a multifunctional agent to fight gram-negative bacteria in vivo.
Transcriptional and Translational Analysis of Biofilm Determinants of
Aggregatibacter actinomycetemcomitans
in Response to Environmental Perturbation
Authors: Amarasinghe Jayaleka J. , Scannapieco Frank A. , Haase Elaine M. 
Published: May 2009

ABSTRACT

Fimbriae, lipopolysaccharide (LPS), and extracellular polymeric substance (EPS) all contribute to biofilm formation by the periodontopathogen
Aggregatibacter actinomycetemcomitans
. To understand how individual biofilm determinants respond to changing environmental conditions, the transcription of genes responsible for fimbria, LPS, and EPS production, as well as the translation of these components, was determined in rough (Rv) and isogenic smooth (Sv) variants of
A. actinomycetemcomitans
cultured in half-strength and full-strength culture medium under anaerobic or aerobic conditions, and in iron-supplemented and iron-chelated medium. The transcription of
tadV
(fimbrial assembly),
pgaC
(extracellular polysaccharide synthesis), and
orf8
or
rmlB
(lipopolysaccharide synthesis) was measured by real-time PCR. The amounts of fimbriae, LPS, and EPS were also estimated from stained sodium dodecyl sulfate-polyacrylamide gels and verified by Western blotting and enzyme-linked immunoadsorbent assay using specific antibodies. Each gene was significantly upregulated in the Rv compared to in the Sv. The transcription of fimbrial, LPS, and EPS genes in the Rv was increased approximately twofold in cells cultured in full-strength medium under anaerobic conditions compared to that in cells cultured under aerobic conditions. Under anaerobic conditions, the transcription of fimbrial and EPS enzymes was elevated in both Rv and Sv cells cultured in half-strength medium, compared to that in full-strength medium. Iron chelation also increased the transcription and translation of all biofilm determinants compared to their expression with iron supplementation, yet the quantity of biofilm was not significantly changed by any environmental perturbation except iron limitation. Thus, anaerobic conditions, nutrient stress, and iron limitation each upregulate known biofilm determinants of
A. actinomycetemcomitans
to contribute to biofilm formation.
ace
, Which Encodes an Adhesin in
Enterococcus faecalis
, Is Regulated by Ers and Is Involved in Virulence
Authors: Lebreton Francois , Riboulet-Bisson Eliette , Serror Pascale , Sanguinetti Maurizio , Posteraro Brunella , Torelli Riccardo , Hartke Axel , Auffray Yanick , Giard Jean-Christophe 
Published: May 2009

ABSTRACT

Enterococcus faecalis
is an opportunistic pathogen that causes numerous infectious diseases in humans and is a major agent of nosocomial infections. In this work, we showed that the recently identified transcriptional regulator Ers (PrfA like), known to be involved in the cellular metabolism and the virulence of
E. faecalis
, acts as a repressor of
ace
, which encodes a collagen-binding protein. We characterized the promoter region of
ace
, and transcriptional analysis by reverse transcription-quantitative PCR and mobility shift protein-DNA binding assays revealed that Ers directly regulates the expression of
ace
. Transcription of
ace
appeared to be induced by the presence of bile salts, probably via the deregulation of
ers
. Moreover, with an
ace
deletion mutant and the complemented strain and by using an insect (
Galleria mellonella
) virulence model, as well as in vivo-in vitro murine macrophage models, we demonstrated for the first time that Ace can be considered a virulence factor for
E. faecalis
. Furthermore, animal experiments revealed that Ace is also involved in urinary tract infection by
E. faecalis
.
Quantifying the growth of arbuscular mycorrhizal fungi: usefulness of the fractal dimension
Authors: Juge Christine , Champagne Annie , Coughlan Andrew P. , Juge Nicolas , Parrott Lael , Piché Yves 
Published: May 2009

The present study is, to the best of our knowledge, the first to investigate the use of the fractal dimension (FD) to quantify the growth and development of undisturbed, fully functional arbuscular mycorrhizal (AM) hyphae developing in vitro. The majority of the work focused on the model AM fungus Glomus intraradices DAOM 181602. The time course study and final measurements of an intact mature extraradical mycelium allowed us to compare the development of the mycelium and the FD value. The final FD value of 1.62 for the mature mycelium is similar to that obtained for highly branched root systems and tree crowns. The FD method was used to characterize the morphology of germinative and presymbiotic hyphae in the presence of stimulatory (strigolactone GR-24, 0.1 µmol·L–1and bisphenol A, 10 µmol·L–1) and inhibitory (NaCl, 80 mmol·L–1) molecules, and the extraradical phase in the presence of an inhibitory molecule (NaCl, 80 mmol·L–1). Where possible, results were compared with those obtained using the traditional grid-line (GL) technique. The FD approach allowed treatment effects to be accurately quantified, both in germinative and extraradical phases. In the second case, this technique provided a single quantitative value of extraradical hyphal growth that included runner hyphae (RH) networks, and fine-branching (FB) ramifications. This is in contrast to the GL technique, which provides a value for the estimation of RH, but which is not suitable for accurately measuring FB hyphae. Given the ease with which the FD values can be calculated, and the fact that this method can provide a single value for the quantification of extraradical hyphal growth and development, we suggest that this method is useful for in vitro studies. Furthermore under certain situations of germinative or presymbiotic growth, it may be used in concert with the GL method to provide a greater degree of information about hyphal morphology. The usefulness and limits of the FD method at different stages of the AM fungal growth cycle are discussed.
The Jurassic and Cretaceous bony fish record (Actinopterygii, Dipnoi) from Thailand
Authors: Cavin Lionel , Deesri Uthumporn , Suteethorn Varavudh 
Published: May 2009

Abstract

This first overview of the bony fish record from the Jurassic and Cretaceous continental deposits of Thailand reveals a significant diversity, with 16 taxa in four formations (the Khlong Min, Phu Kradung, Sao Khua and Khok Kruat Fms). Four of these taxa have already been diagnosed and described, and a couple of others are sufficiently well preserved to be diagnosed in the future. The other taxa are represented at present by fragmentary and isolated remains. The highest diversity is observed among ‘semionotids’, which occur in the four formations. Sinamiids are represented by at least three taxa that occur only in the Sao Khua and the Khok Kruat Formations. Pycnodont fishes are known by rare and isolated dentitions and teeth in the Khlong Min and Sao Khua Formations, and lungfishes referred to
Ferganoceratodus
occur in the Khlong Min and the Phu Kradung Formations. The assemblages provide few palaeogeographical indications at present, except for evidence of relationships with China and Central Asia. However, it is expected than once the phylogenetic relationships of these taxa are resolved, we will be able to reconstruct precise palaeogeographical scenarios.
Turtle assemblages of the Khorat Group (Late Jurassic-Early Cretaceous) of NE Thailand and their palaeobiogeographical significance
Authors: Tong Haiyan , Claude Julien , Suteethorn Varavudh , Naksri Wilailuck , Buffetaut Eric 
Published: May 2009

Abstract

The turtle assemblages from the Khorat Group consist mainly of trionychoids. They include the primitive Trionychoidae
Basilochelys
and basal eucryptodiran turtles from the Phu Kradung Formation (?Late Jurassic); the adocid
Isanemys srisuki
, the carettochelyid
Kizylkumemys
sp. and undetermined Trionychoidea from the Sao Khua Formation (Early Cretaceous); and the carettochelyid
Kizylkumemys khoratensis
and the adocid
Shachemys
sp. from the Khok Kruat Formation (Aptian). Our study shows some faunal links between the turtle faunas from the Khorat Group and those from the peripheral regions of Asia during the time span of the Khorat Group. Thus the coastal regions of Asia, and more particularly SE Asia, may have been important places for the origin and early diversification of the trionychoids.
Khoratosuchus jintasakuli
gen. et sp. nov., an advanced neosuchian crocodyliform from the Early Cretaceous (Aptian-Albian) of NE Thailand
Authors: Lauprasert K. , Cuny G. , Thirakhupt K. , Suteethorn V. 
Published: May 2009

Abstract

A new slender-snouted neosuchian crocodyliform,
Khoratosuchus jintasakuli
gen. et sp. nov., is described from the late Early Cretaceous Khok Kruat Formation of NE Thailand. This discovery represents the youngest and most advanced Mesozoic crocodyliform known in Thailand on the basis of the following cranial features: the secondary choanae are relatively posterior and almost enclosed by the pterygoid; the lateral margin of the maxilla is relatively straight without lateral constrictions; the dorsal surface of the skull lacks ridges and fossae; maxillary teeth are homodontous; the anterior end of the jugal and prefrontal terminate at the same level. The specimen bears resemblances to Chinese and European derived neosuchians and suggests a close relationship between the late Early Cretaceous neosuchians of China, Europe and SE Asia.
A new skeleton of
Phuwiangosaurus sirindhornae
(Dinosauria, Sauropoda) from NE Thailand
Authors: Suteethorn S. , Le Loeuff J. , Buffetaut E. , Suteethorn V. , Talubmook C. , Chonglakmani C. 
Published: May 2009

Abstract

A new skeleton of a sauropod dinosaur has been discovered in the Early Cretaceous Sao Khua Formation at Ban Na Khrai in Changwat Kalasin (NE Thailand). All sauropod bones from Ban Na Khrai share all their characteristics with the type specimen of
Phuwiangosaurus sirindhornae
Martin, Buffetaut & Suteethorn 1994
. The 60% complete skeleton is very well preserved and includes cranial elements (a tooth, a frontal, a postorbital, a squamosal, both quadrates, and the braincase), whereas the type specimen is only 10% complete and consists of postcranial bones only. The material from Ban Na Khrai belongs to a single subadult individual of
Phuwiangosaurus
, as attested by the unfused neurocentral sutures of the vertebrae, which are firmly fused and larger in size in the holotypic specimen.
Bone histology and its implications for the life history and growth of the Early Cretaceous titanosaur
Phuwiangosaurus sirindhornae
Authors: Klein Nicole , Sander Martin , Suteethorn Varavudh 
Published: May 2009

Abstract

Bone histology is the most comprehensive way of obtaining data on growth and life history for dinosaurs. Humeri and femora of the basal titanosaur
Phuwiangosaurus sirindhornae
from the Early Cretaceous of Thailand were sampled by core drilling. The sample represents growth series with humeri ranging in size from 71.0 to 110.0 cm and femora ranging in size from 38.5 to 112.0 cm. The bone tissue is continuously growing laminar fibro-lamellar bone typical for virtually all sauropods. Several ontogenetic stages can be distinguished, and a general growth pattern is deduced on the basis of different-sized individuals. Humeri differ from femora in generally showing more remodelling by secondary osteons.
Ichnological evidence for small quadrupedal ornithischians from the basal Cretaceous of SE Asia and North America: implications for a global radiation
Authors: Lockley Martin G. , McCrea Richard T. , Matsukawa Masaki 
Published: May 2009

Abstract

Tracks of small quadrupedal ornithischians with five manual and four pedal digits have been recorded from sedimentary rocks near the Late Jurassic–Early Cretaceous (Tithonian–Berriasian) boundary in NE Thailand and British Columbia. These are compared with larger tracks of gracile, quadrupedal ornithopods from the earliest Cretaceous of Spain and smaller tracks of a quadruped of unknown age from Zimbabwe. The Thai and Canadian tracks are similar to the Early Jurassic (Liassic) ichnogenus
Anomoepus
and the small ornithopod tracks from the Late Jurassic of Spain. They are the only known post-Liassic ornithischian tracks in which up to five discrete manus digit impressions are clearly visible. Based on strong heteropody (manus much smaller than pes) in all cases we infer an ornithopod trackmaker rather than another ornithischian. The scattered, but widespread earliest Cretaceous occurrence of this ichnotaxon, herein assigned to
Neoanomoepus perigrinatus
ichnogen. and ichnosp. nov., on the basis of type material from Canada, suggests that these hitherto unknown earliest Cretaceous ichnofaunas may represent a radiation of small basal ornithopods (pes length less than 15 cm), appearing before the widespread radiation of large ornithopods (pes length up to 60 cm or more) later in the Neocomian (Valanginian–Barremian), Aptian–Albian and Late Cretaceous. The primitive condition of the trackmaker is indicated by the pedal and manual morphology, which consists of four and five digits respectively that are not enclosed by well-developed fleshy padding or integument. In contrast, all larger Cretaceous ornithopod tracks, mostly from post-Berriasian strata, have only three pedal digits enclosed in fleshy pads and a manus in which all functional digits are reduced and enclosed by substantial flesh.
Late Palaeozoic and Mesozoic tectonic and palaeogeographical evolution of SE Asia
Authors: Metcalfe Ian 
Published: May 2009

Abstract
SE Asia comprises a collage of continental terranes derived directly or indirectly from the India–Australian margin of eastern Gondwana. The Late Palaeozoic and Mesozoic evolution of the region involved the rifting and separation of three elongate continental slivers from eastern Gondwana and the successive opening and closure of three ocean basins, the Palaeo-Tethys, Meso-Tethys and Ceno-Tethys. The Sukhothai Island Arc System, including the Linchang, Sukhothai and Chanthaburi terranes, is identified between the Sibumasu and Indochina–East Malaya terranes in SE Asia and was formed by back-arc spreading in the Permian. The Jinghong, Nan–Uttaradit and Sra Kaeo sutures represent the closed back-arc basin. The Palaeo-Tethys is represented to the west by the Changning–Menglian, Chiang Mai/Inthanon and Bentong–Raub suture zones. The West Sumatra and West Burma blocks rifted and separated from Gondwana, along with Indochina and East Malaya in the Devonian, and together with South China formed a composite terrane ‘Cathaysialand’ in the Permian. They were translated westwards to their positions outboard of the Sibumasu Terrane by strike-slip tectonics in the Late Permian–Early Triassic at the zone of convergence between the Meso-Tethys and Palaeo-Pacific plates. SW Borneo is tentatively identified as possibly being the missing ‘Argoland’ that separated from NW Australia in the Jurassic. Palaeogeographical reconstructions for the Late Palaeozoic and Mesozoic illustrating the tectonic and palaeogeographical evolution of SE Asia are presented.