bluuebunny/crossref_metadata_2025_split huggingface dataset:
Role of a Sodium-Dependent Symporter Homologue in the Thermosensitivity of β-Lactam Antibiotic Resistance and Cell Wall Composition in
Staphylococcus aureus
Authors: Sieradzki Krzysztof , Chung Marilyn , Tomasz Alexander 
Published: December 2007

ABSTRACT

Expression of high-level β-lactam resistance is known to be thermosensitive in many methicillin-resistant
Staphylococcus aureus
(MRSA) strains, including strain COL, in which the high methicillin MIC for cultures grown at 37°C (800 μg/ml) was reduced to 12 μg/ml at 42°C. COL grew faster at 42°C than at 37°C and at the higher temperature produced cell walls of abnormal composition: there was an over-representation of the monomeric muropeptide without the oligoglycine chain and an increase in the representation of multimers that contained this wall component as the donor molecule. Screening of a Tn
551
insertional library for mutants, in which the high and homogenous β-lactam antibiotic resistance of strain COL is retained at 42°C, identified mutant C245, which expressed high-level methicillin resistance and produced a cell wall of normal composition independent of the temperature. The Tn
551
inactivated gene was found, by homology search, to encode for a sodium-dependent symporter, homologues of which are ubiquitous in both prokaryotic and eukaryotic genomes. Inactivation of this putative symporter in several heteroresistant clinical MRSA isolates caused striking increases in the level of their β-lactam resistance.
Pharmacokinetic Interaction between Fosamprenavir-Ritonavir and Rifabutin in Healthy Subjects
Authors: Ford Susan L. , Chen Ya-Chi , Lou Yu , Borland Julie , Min Sherene S. , Yuen Geoffrey J. , Shelton Mark J. 
Published: December 2007

ABSTRACT

Rifabutin (RFB) is administered for treatment of tuberculosis and
Mycobacterium avium
complex infection, including use for patients coinfected with human immunodeficiency virus (HIV). Increased systemic exposure to RFB and its equipotent active metabolite, 25-
O
-desacetyl-RFB (dAc-RFB), has been reported during concomitant administration of CYP3A4 inhibitors, including ritonavir (RTV), lopinavir, and amprenavir (APV); therefore, a reduction in the RFB dosage is recommended when it is coadministered with these protease inhibitors. Fosamprenavir (FPV), the phosphate ester prodrug of the HIV type 1 protease inhibitor APV, is administered either with or without RTV. A randomized, open-label, two-period, two-sequence, balanced, crossover drug interaction study was conducted with 22 healthy adult subjects to compare steady-state plasma RFB pharmacokinetic parameters during concomitant administration of FPV-RTV (700/100 mg twice a day [BID]) with a 75%-reduced RFB dose (150 mg every other day [QOD]) to the standard RFB regimen (300 mg once per day [QD]) by geometric least-squares mean ratios. Relative to results with RFB (300 mg QD), coadministration of dose-adjusted RFB with FPV-RTV resulted in an unchanged RFB area under the concentration-time curve for 0 to 48 h (AUC
0-48
) and a 14% decrease in the maximum concentration of drug in plasma (
C
max
), whereas the AUC
0-48
and
C
max
of dAc-RFB were increased by 11- and 6-fold, respectively, resulting in a 64% increase in the total antimycobacterial AUC
0-48
. Relative to historical controls, the plasma APV AUC from 0 h to the end of the dosing interval (AUC
0-τ
) and
C
max
were increased ∼35%, and the concentration at the end of the dosing interval at steady state was unchanged following coadministration of RFB with FPV-RTV. The safety profile of the combination of RFB and FPV-RTV was consistent with previously described events with RFB or FPV-RTV alone. Based on the results of this study, a reduction in the RFB dose by ≥75% (to 150 mg QOD or three times per week) is recommended when it is coadministered with FPV-RTV (700/100 mg BID).
Telithromycin and Quinupristin-Dalfopristin Induce Delayed Death in
Plasmodium falciparum
Authors: Barthel Diana , Schlitzer Martin , Pradel Gabriele 
Published: December 2007

ABSTRACT

Antibacterial agents are used in malaria therapy due to their effect on two prokaryote organelles, the mitochondrion and the apicoplast. We demonstrate here that the ribosome-blocking antibiotics telithromycin and quinupristin-dalfopristin, but not linezolid, inhibit the growth of
Plasmodium falciparum
. Both drugs induce delayed death in the parasite, suggesting that their effect involves the impairment of apicoplast translation processes.
Vancomycin-Resistant
Staphylococcus aureus
Isolates Associated with Inc18-Like
vanA
Plasmids in Michigan
Authors: Zhu Wenming , Clark Nancye C. , McDougal Linda K. , Hageman Jeffery , McDonald L. Clifford , Patel Jean B. 
Published: December 2007

ABSTRACT

Five of the seven cases of vancomycin-resistant
Staphylococcus aureus
(VRSA) infection identified to date have occurred in southeastern Michigan. VRSA isolates from the four most recent cases (all from Michigan) were characterized. The
vanA
gene was localized to a single plasmid in each VRSA isolate. The pulsed-field gel electrophoresis patterns of chromosomal DNA and the restriction profile of the plasmid demonstrated that the four isolates were unique and differed from the first three VRSA isolates. Vancomycin-resistant
Enterococcus
(VRE) isolates, all of which were
Enterococcus faecalis
, were recovered from case patients 4 to 6. Each VRE isolate transferred vancomycin resistance to
E. faecalis
JH2-2 by conjugation. PCRs for
vanA
and the Inc18-like plasmid genes
traA
and
repR
confirmed the presence of an Inc18-like
vanA
plasmid in all VRE isolates and transconjugants. An Inc18-like
vanA
plasmid was identified in the VRSA isolate from case patient 7. These findings suggest a role of Inc18-like plasmids as
vanA
donors.
In Vitro Interactions between Tacrolimus and Azoles against
Candida albicans
Determined by Different Methods
Authors: Sun Shujuan , Li Yan , Guo Qiongjie , Shi Changwen , Yu Jinlong , Ma Lin 
Published: December 2007

ABSTRACT

Combination therapy could be of use for the treatment of fungal infections, especially those caused by drug-resistant fungi. However, the methods and approaches used for data generation and result interpretation need further optimizing. The fractional inhibitory concentration index (FICI) is the most commonly used method, but it has several drawbacks in characterizing antifungal drug interaction. Alternatively, some new methods can be used such as the Δ
E
model (difference between the predicted and measured fungal growth percentages) and the response surface approach, which uses the concentration-effect relationship over the whole concentration range instead of just the MIC. In the present study, in vitro interactions between tacrolimus (FK506) and three azoles—fluconazole (FLC), itraconazole (ITR), and voriconazole (VRC)-against
Candida albicans
were evaluated by the checkerboard microdilution method and time-killing test. The intensity of the interactions was determined by visual reading and the spectrophotometric method in a checkerboard assay, and the nature of the interactions was assessed by nonparametric models of FICI and Δ
E
. Colony counting and colorimetric viable detection methods (2,3-bis {2-methoxy-4-nitro-5-[(sulfenylamino) carbonyl]-2H-tetrazolium hydroxide} [XTT] reduction test) were used for evaluating the combination antifungal effects over time. Synergistic and indifferent effects were found for the combination of FK506 and azoles against azole-sensitive strains, while strong synergy was found against azole-resistant strains analyzed by FICI. The Δ
E
model gave more consistent results with FICI. The positive interactions were also confirmed by the time-killing test. Our findings suggest a potential role for combination therapy with calcineurin pathway inhibitors and azoles to augment activity against resistant
C. albicans
.
Inhibition of ABC Transporters Abolishes Antimony Resistance inLeishmaniaInfection
Authors: Mookerjee Basu Jayati , Mookerjee Ananda , Banerjee Rajdeep , Saha Manik , Singh Subhankar , Naskar Ksudiram , Tripathy Gayetri , Sinha Prabhat K. , Pandey Krishna , Sundar Shyam , Bimal Sanjeev , Das Pradip K. , Choudhuri Soumitra K. , Roy Syamal 
Published: December 2007

ABSTRACTThe emergence of antimony (Sb) resistance has jeopardized the treatment of visceral leishmaniasis in various countries. Previous studies have considered the part played by leishmanial parasites in antimony resistance, but the involvement of host factors in the clinical scenario remained to be investigated. Here we show that unlike infection with Sb-sensitive (Sbs)Leishmania donovani, infection with Sb-resistant (Sbr)L. donovaniinduces the upregulation of multidrug resistance-associated protein 1 (MRP1) and permeability glycoprotein (P-gp) in host cells, resulting in a nonaccumulation of intracellular Sb following treatment with sodium antimony gluconate (SAG) favoring parasite replication. The inhibition of MRP1 and P-gp with resistance-modifying agents such as lovastatin allows Sb accumulation and parasite killing within macrophages and offers protection in an animal model in which infection with SbrL. donovaniis otherwise lethal. The occurrence of a similar scenario in clinical cases is supported by the findings that unlike monocytes from SAG-sensitive kala-azar (KA) patients, monocytes from SAG-unresponsive KA patients overexpress P-gp and MRP1 and fail to accumulate Sb following in vitro SAG treatment unless pretreated with inhibitors of ABC transporters. Thus, the expression status of MRP1 and P-gp in blood monocytes may be used as a diagnostic marker for Sb resistance and the treatment strategy can be designed accordingly. Our results also indicate that lovastatin, which can inhibit both P-gp and MRP1, might be beneficial for reverting Sb resistance in leishmaniasis as well as drug resistance in other clinical situations, including cancer.
MisR/MisS Two-Component Regulon in
Neisseria meningitidis
Authors: Tzeng Yih-Ling , Kahler Charlene M. , Zhang Xinjian , Stephens David S. 
Published: December 2007

ABSTRACT

Two-component regulatory systems are involved in processes important for bacterial pathogenesis. Inactivation of the
misR
/
misS
system in
Neisseria meningitidis
results in the loss of phosphorylation of the lipooligosaccharide inner core and causes attenuation in a mouse model of meningococcal infection. One hundred seventeen (78 up-regulated and 39 down-regulated) potential regulatory targets of the MisR/MisS (MisR/S) system were identified by transcriptional profiling of the NMB
misR
mutant and the parental wild-type meningococcal strain NMB. The regulatory effect was further confirmed in a subset of target genes by quantitative real-time PCR and β-galactosidase transcriptional fusion reporter assays. The MisR regulon includes genes encoding proteins necessary for protein folding in the bacterial cytoplasm and periplasm, transcriptional regulation, metabolism, iron assimilation, and type I protein transport. Mutation in the MisR/S system caused increased sensitivity to oxidative stress and also resulted in decreased susceptibility to complement-mediated killing by normal human serum. To identify the direct targets of MisR regulation, electrophoretic mobility shift assays were carried out using purified MisR-His
6
protein. Among 22 genes examined,
misR
directly interacted with 14 promoter regions. Six promoters were further investigated by DNase I protection assays, and a MisR-binding consensus sequence was proposed. Thus, the direct regulatory targets of MisR and the minimal regulon of the meningococcal MisR/S two-component signal transduction system were characterized. These data indicate that the MisR/S system influences a wide range of biological functions in
N. meningitidis
either directly or via intermediate regulators.
Neutrophils Contribute to Development of a Protective Immune Response during Onset of Infection withLeishmania donovani
Authors: McFarlane Emma , Perez Cynthia , Charmoy Mélanie , Allenbach Cindy , Carter K. Christine , Alexander James , Tacchini-Cottier Fabienne 
Published: December 2007

ABSTRACTNeutrophils are key components of the inflammatory response and as such contribute to the killing of microorganisms. In addition, recent evidence suggests their involvement in the development of the immune response. The role of neutrophils during the first weeks post-infection withLeishmania donovaniwas investigated in this study. WhenL. donovani-infected mice were selectively depleted of neutrophils with the NIMP-R14 monoclonal antibody, a significant increase in parasite numbers was observed in the spleen and bone marrow and to a lesser extent in the liver. Increased susceptibility was associated with enhanced splenomegally, a delay in the maturation of hepatic granulomas, and a decrease in inducible nitric oxide synthase expression within granulomas. In the spleen, neutrophil depletion was associated with a significant increase in interleukin 4 (IL-4) and IL-10 levels and reduced gamma interferon secretion by CD4+and CD8+T cells. Increased production of serum IL-4 and IL-10 and higher levels ofLeishmania-specific immunoglobulin G1 (IgG1) versus IgG2a revealed the preferential induction of Th2 responses in neutrophil-depleted mice. Altogether, these data suggest a critical role for neutrophils in the early protective response againstL. donovani, both as effector cells involved in the killing of the parasites and as significant players influencing the development of a protective Th1 immune response.
Neural Correlates of Preparation for Action Selection as a Function of Specific Task Demands
Authors: Donohue S. E. , Wendelken C. , Bunge Silvia A. 
Published: December 2007

Abstract
Our behavior is frequently guided by rules, or prescribed guides for action. The prefrontal cortex (PFC) has been implicated in the ability to retrieve and use rules in a conscious, effortful manner. Several functional magnetic resonance imaging (fMRI) studies have examined the role of the PFC in rule representation; however, the precise PFC subregions implicated in this function vary from study to study. This observation raises the question of whether there are distinct classes of rules that are represented differentially in the brain. To address this question, an fMRI study was conducted in which participants performed two tasks, each at two levels of difficulty, during acquisition of event-related fMRI data. The response competition task was based on the Stroop paradigm: Participants were cued to determine either the ink color or color name associated with a word stimulus. In contrast, the paired associates task evaluated participants' memory for either one or four previously memorized pairs of words. On each trial, an instructional cue appeared briefly on the screen, followed by an 8-sec delay and a probe period. The left ventrolateral PFC (VLPFC) and the left supplementary motor area (SMA)/pre-SMA were engaged during the delay period for all conditions, consistent with a general role in rule representation. In contrast, different parts of the dorsolateral PFC, the anterior PFC, and the right VLPFC were preferentially engaged by one or both of the more challenging rules, consistent with the idea that rules are represented by partially distinct brain structures according to their content.
Error and Deviance Processing in Implicit and Explicit Sequence Learning
Authors: Ferdinand Nicola K. , Mecklinger Axel , Kray Jutta 
Published: December 2007

Abstract
In this experiment, we examined the extent to which error-driven learning may operate under implicit learning conditions. We compared error monitoring in a sequence learning task in which stimuli consisted of regular, irregular, or random sequences. Subjects were either informed (explicit condition) or not informed (implicit condition) about the existence of the sequence. For both conditions, reaction times were faster to stimuli from regular sequences than from random sequences, thus supporting the view that sequence learning occurs irrespective of learning condition. Response-locked event-related potentials (ERPs) showed a pronounced ERN/Ne, thereby signaling the detection of committed errors. Deviant stimuli from irregular sequences elicited an N2b component that developed in the course of the experiment, albeit faster for explicit than implicit learners. This observation supports the view that deviant events acquire the status of perceived errors during explicit and implicit learning, and thus, an N2b is generated resembling the ERN/Ne to committed errors. While performing the task, expectations about upcoming events are generated, compared to the actual events, and evaluated on the dimension “better or worse than expected.” The accuracy of this process improves with learning, as shown by a gradual increase in N2b amplitude as a function of learning. Additionally, a P3b, which is thought to mirror conscious processing of deviant stimuli and is related to updating of working memory representations, was found for explicit learners only.
The Functional Effect of Transcranial Magnetic Stimulation: Signal Suppression or Neural Noise Generation?
Authors: Harris Justin A. , Clifford Colin W. G. , Miniussi Carlo 
Published: December 2007

Abstract
Transcranial magnetic stimulation (TMS) is a popular tool for mapping perceptual and cognitive processes in the human brain. It uses a magnetic field to stimulate the brain, modifying ongoing activity in neural tissue under the stimulating coil, producing an effect that has been likened to a “virtual lesion.” However, research into the functional basis of this effect, essential for the interpretation of findings, lags behind its application. Acutely, TMS may disable neuronal function, thereby interrupting ongoing neural processes. Alternatively, the effects of TMS have been attributed to an injection of “neural noise,” consistent with its immediate and effectively random depolarization of neurons. Here we apply an added-noise paradigm to test these alternatives. We delivered TMS to the visual cortex and measured its effect on a simple visual discrimination task, while concurrently manipulating the level of image noise in the visual stimulus itself. TMS increased thresholds overall; and increasing the amount of image noise systematically increased discrimination thresholds. However, these two effects were not independent. Rather, TMS interacted multiplicatively with the image noise, consistent with a reduction in the strength of the visual signal. Indeed, in this paradigm, there was no evidence that TMS independently added noise to the visual process. Thus, our findings indicate that the “virtual lesion” produced by TMS can take the form of a loss of signal strength which may reflect a momentary interruption to ongoing neural processing.
Dissociable Neural Effects of Task Order Control and Task Set Maintenance during Dual-task Processing
Authors: Stelzel Christine , Kraft Antje , Brandt Stephan A. , Schubert Torsten 
Published: December 2007

Abstract
The functional relevance of the lateral prefrontal cortex (lPFC) for the ability to process two tasks simultaneously has been debated extensively in previous studies that employed functional magnetic resonance imaging (fMRI) to investigate the neural correlates of dual-task processing. In the present fMRI study, we shed new light on this debate by directly comparing the lPFC activity changes for two cognitive functions commonly associated with dual-task performance: task order control and task set maintenance. We manipulated both functions in a 2 × 2 integrated parametric design. The fMRI data revealed a functional-neuroanatomical dissociation for the lPFC. Regions surrounding the inferior frontal sulcus and the middle frontal gyrus were exclusively associated with task order control but not with increased demands on task set maintenance during dual-task processing. The only lPFC region associated with task set maintenance was located in the left anterior insula. Outside the lPFC, we found dissociable regions for task order control and task set maintenance bilaterally in the premotor cortices with more rostral premotor activity for task order control and more caudal premotor activity for task set maintenance. In addition, task order control activated the intraparietal sulci bilaterally. Our data clearly suggest that task order control is a separable cognitive mechanism in dual-task situations that is related to activity changes in the lPFC and that can be dissociated from task set maintenance.
The Neural Integration of Speaker and Message
Authors: Van Berkum Jos J. A. , van den Brink Danielle , Tesink Cathelijne M. J. Y. , Kos Miriam , Hagoort Peter 
Published: December 2007

Abstract
When do listeners take into account who the speaker is? We asked people to listen to utterances whose content sometimes did not match inferences based on the identity of the speaker (e.g., “If only I looked like Britney Spears” in a male voice, or “I have a large tattoo on my back” spoken with an upper-class accent). Event-related brain responses revealed that the speaker's identity is taken into account as early as 200–300 msec after the beginning of a spoken word, and is processed by the same early interpretation mechanism that constructs sentence meaning based on just the words. This finding is difficult to reconcile with standard “Gricean” models of sentence interpretation in which comprehenders initially compute a local, context-independent meaning for the sentence (“semantics”) before working out what it really means given the wider communicative context and the particular speaker (“pragmatics”). Because the observed brain response hinges on voice-based and usually stereotype-dependent inferences about the speaker, it also shows that listeners rapidly classify speakers on the basis of their voices and bring the associated social stereotypes to bear on what is being said. According to our event-related potential results, language comprehension takes very rapid account of the social context, and the construction of meaning based on language alone cannot be separated from the social aspects of language use. The linguistic brain relates the message to the speaker immediately.
“Brain Is to Thought as Stomach Is to ??”: Investigating the Role of Rostrolateral Prefrontal Cortex in Relational Reasoning
Authors: Wendelken Carter , Nakhabenko Denis , Donohue Sarah E. , Carter Cameron S. , Bunge Silvia A. 
Published: December 2007

AbstractBrain imaging studies suggest that the rostrolateral prefrontal cortex (RLPFC), is involved in relational reasoning. Functional magnetic resonance imaging (fMRI) studies involving Raven's Progressive Matrices or verbal propositional analogies indicate that the RLPFC is engaged by tasks that require integration across multiple relational structures. Several studies have shown that the RLPFC is more active when people must evaluate an analogy (e.g., Is shoe to foot as glove is to hand?) than when they must simply evaluate two individual semantic relationships, consistent with the hypothesis that this region is important for relational integration. The current fMRI investigation further explores the role of the RLPFC in reasoning and relational integration by comparing RLPFC activation across four different propositional analogy conditions. Each of the four conditions required either relation completion (e.g., Shoe is to foot as glove is to WHAT? → “hand”) or relation comparison (e.g., Is shoe to foot as glove is to hand? → “yes”). The RLPFC was engaged more strongly by the comparison subtask relative to completion, suggesting that the RLPFC is particularly involved in comparing relational structures.