bluuebunny/crossref_metadata_2025_split huggingface dataset:
Cholinergic modulation of neuronal excitability and recurrent excitation‐inhibition in prefrontal cortex circuits: implications for gamma oscillations
Authors: Pafundo Diego E. , Miyamae Takeaki , Lewis David A. , Gonzalez‐Burgos Guillermo 
Published: July 2013

Key points
Previous studies indicate that cholinergic neuromodulation is required for cognitive processes and for gamma oscillatory activity in neocortical networks in vivo. The cholinergic agonist carbachol (CCh) induces gamma oscillations in vitro, via mechanisms that may be shared with those mediating in vivo gamma oscillations.
Here, we studied the effects of CCh on cortical circuit components thought to be critical for gamma oscillations, and found that CCh stimulated firing of pyramidal cells (PCs) and increased excitatory synaptic input onto fast‐spiking interneurons (FSNs).
CCh also modulated synaptic transmission between FSNs and PCs, decreasing synaptic depression during repetitive presynaptic firing, while simultaneously reducing the unitary synaptic currents.
CCh increased the probability of neuron firing per oscillation cycle when PCs and FSNs fired in response to oscillatory input at gamma frequency.
Combined, these effects of CCh may help explain the contribution of cholinergic modulation to gamma oscillations.
Abstract  Cholinergic neuromodulation in neocortical networks is required for gamma oscillatory activity associated with working memory and other cognitive processes. Importantly, the cholinergic agonist carbachol (CCh) induces gamma oscillations in vitro, via mechanisms that may be shared with in vivo gamma oscillations and that are consistent with the pyramidal interneuron network gamma (PING) model. In PING oscillations, pyramidal cells (PCs), driven by asynchronous excitatory input, recruit parvalbumin‐positive fast‐spiking interneurons (FSNs), which then synchronize the PCs via feedback inhibition. Whereas the PING model is favoured by current data, how cholinergic neuromodulation contributes to gamma oscillation production is poorly understood. We thus studied the effects of cholinergic modulation on circuit components of the PING model in mouse medial prefrontal cortex (mPFC) brain slices. CCh depolarized and evoked action potential firing in a fraction of PCs and increased excitatory synaptic input onto FSNs. In synaptically connected pairs, CCh reduced the short‐term depression at FSN–PC and PC–FSN synapses, equalizing synaptic strength during repetitive presynaptic firing while simultaneously increasing the failure probability. Interestingly, when PCs or FSNs fired in response to gamma frequency oscillatory inputs, CCh increased the firing probability per cycle. Combined with the equalization of synaptic strength, an increase by CCh in the fraction of neurons recruited per oscillation cycle may support oscillatory synchrony of similar strength during relatively long oscillation episodes such as those observed during working memory tasks, suggesting a significant functional impact of cholinergic modulation of mPFC circuit components crucial for the PING model.
Establishment of a Method To Rapidly Assay Bacterial Persister Metabolism
Authors: Orman Mehmet A. , Brynildsen Mark P. 
Published: July 2013

ABSTRACT

Bacterial persisters exhibit an extraordinary tolerance to antibiotics that is dependent on their metabolic state. Although persister metabolism promises to be a rich source of antipersister strategies, there is relatively little known about the metabolism of these rare and transient phenotypic variants. To address this knowledge gap, we explored the use of several techniques, and we found that only one measured persister metabolism. This assay was based on the phenomenon of metabolite-enabled aminoglycoside killing of persisters, and we used it to characterize the metabolic heterogeneity of different persister populations. From these investigations, we determined that glycerol and glucose are the most ubiquitously used carbon sources by various types of
Escherichia coli
persisters, suggesting that these metabolites might prove beneficial to deliver in conjunction with aminoglycosides for the treatment of chronic and recurrent infections. In addition, we demonstrated that the persister metabolic assay developed here is amenable to high-throughput screening with the use of phenotype arrays.
Tigecycline Induction of Phenol-Soluble Modulins by Invasive Methicillin-Resistant Staphylococcus aureus Strains
Authors: Yamaki Jason , Synold Timothy , Wong-Beringer Annie 
Published: July 2013

ABSTRACT

We examined the effects of tigecycline on three types of exoproteins, α-type phenol-soluble modulins (PSMα
1
to PSMα
4
), α-hemolysin, and protein A, in 13 methicillin-resistant
Staphylococcus aureus
isolates compared to those of clindamycin and linezolid. Paradoxical increases in PSMαs occurred in 77% of the isolates with tigecycline at 1/4 and 1/8 MICs and clindamycin at 1/8 MIC compared to only 23% of the isolates with linezolid at 1/8 MIC. Induction was specific to PSMα
1
to PSMα
4
, as protein A and α-hemolysin production was decreased under the same conditions by all of the antibiotics used.
Characterization of Tn
5801.Sag
, a Variant of Staphylococcus aureus Tn
916
Family Transposon Tn
5801
That Is Widespread in Clinical Isolates of Streptococcus agalactiae
Authors: Mingoia Marina , Morici Eleonora , Tili Emily , Giovanetti Eleonora , Montanari Maria Pia , Varaldo Pietro E. 
Published: July 2013

ABSTRACT

Tn
5801
, originally detected in
Staphylococcus aureus
Mu50, is a Tn
916
family element in which a unique
int
gene (

int
5801

) replaces the
int
and
xis
genes in Tn
916
(

int
916

and

xis
916

). Among 62
tet
(M)-positive tetracycline-resistant
Streptococcus agalactiae
isolates, 43 harbored Tn
916
, whereas 19 harbored a Tn
5801
-like element (Tn
5801.Sag
, ∼20.6 kb). Tn
5801.Sag
was characterized (PCR mapping, partial sequencing, and chromosomal integration) and compared to other Tn
5801
-like elements. Similar to Tn
5801
from
S. aureus
Mu50, tested in parallel, Tn
5801.Sag
was unable to undergo circularization and conjugal transfer.
Hyperthermia Sensitizes Rhizopus oryzae to Posaconazole and Itraconazole Action through Apoptosis
Authors: Shirazi Fazal , Pontikos Michael A. , Walsh Thomas J. , Albert Nathaniel , Lewis Russell E. , Kontoyiannis Dimitrios P. 
Published: July 2013

ABSTRACT

The high mortality rate of mucormycosis with currently available monotherapy has created interest in studying novel strategies for antifungal agents. With the exception of amphotericin B (AMB), the triazoles (posaconazole [PCZ] and itraconazole [ICZ]) are fungistatic
in vitro
against
Rhizopus oryzae
. We hypothesized that growth at a high temperature (42°C) results in fungicidal activity of PCZ and ICZ that is mediated through apoptosis.
R. oryzae
had high MIC values for PCZ and ICZ (16 to 64 μg/ml) at 25°C; in contrast, the MICs for PCZ and ICZ were significantly lower at 37°C (8 to 16 μg/ml) and 42°C (0.25 to 1 μg/ml). Furthermore, PCZ and ICZ dose-dependent inhibition of germination was more pronounced at 42°C than at 37°C. In addition, intracellular reactive oxygen species (ROS) increased significantly when fungi were exposed to antifungals at 42°C. Characteristic cellular changes of apoptosis in
R. oryzae
were induced by the accumulation of intracellular reactive oxygen species. Cells treated with PCZ or ICZ in combination with hyperthermia (42°C) exhibited characteristic markers of early apoptosis: phosphatidylserine externalization visualized by annexin V staining, membrane depolarization visualized by bis-[1,3-dibutylbarbituric acid] trimethine oxonol (DiBAC) staining, and increased metacaspase activity. Moreover, terminal deoxynucleotidyltransferase-mediated dUTP-biotin nick end labeling (TUNEL) assay and DAPI (4′,6-diamidino-2-phenylindole) staining demonstrated DNA fragmentation and condensation, respectively. The addition of
N
-acetylcysteine increased fungal survival, prevented apoptosis, reduced ROS accumulation, and decreased metacaspase activation. We concluded that hyperthermia, either alone or in the presence of PCZ or ICZ, induces apoptosis in
R. oryzae
. Local thermal delivery could be a therapeutically useful adjunct strategy for these refractory infections.
Synergistic Effects of Anti-CmeA and Anti-CmeB Peptide Nucleic Acids on Sensitizing Campylobacter jejuni to Antibiotics
Authors: Mu Yang , Shen Zhangqi , Jeon Byeonghwa , Dai Lei , Zhang Qijing 
Published: July 2013

ABSTRACT

The CmeABC efflux pump in
Campylobacter jejuni
confers resistance to structurally divergent antimicrobials, and inhibition of CmeABC represents a promising strategy to control antibiotic-resistant
Campylobacter
. Antisense peptide nucleic acids (PNAs) targeting the three components of CmeABC were evaluated for inhibition of CmeABC expression. The result revealed a synergistic effect of the PNAs targeting CmeA and CmeB on sensitizing
C. jejuni
to antibiotics. This finding further demonstrates the feasibility of using PNAs to potentiate antibiotics against antibiotic-resistant
Campylobacter
.
Human β-Defensin 2 Induces Extracellular Accumulation of Adenosine in Escherichia coli
Authors: Estrela Andreia Bergamo , Rohde Manfred , Gutierrez Maximiliano Gabriel , Molinari Gabriella , Abraham Wolf-Rainer 
Published: July 2013

ABSTRACTHuman β-defensins are host defense peptides performing antimicrobial as well as immunomodulatory functions. The present study investigated whether treatment ofEscherichia coliwith human β-defensin 2 could generate extracellular molecules of relevance for immune regulation. Mass spectrometry analysis of bacterial supernatants detected the accumulation of purine nucleosides triggered by β-defensin 2 treatment. Other cationic antimicrobial peptides tested presented variable outcomes with regard to extracellular adenosine accumulation; human β-defensin 2 was the most efficient at inducing this response. Structural and biochemical evidence indicated that a mechanism other than plain lysis was involved in the observed phenomenon. By use of isotope (13C) labeling, extracellular adenosine was found to be derived from preexistent RNA, and a direct interaction between the peptide and bacterial nucleic acid was documented for the first time for β-defensin 2. Taken together, the data suggest that defensin activity on a bacterial target may alter local levels of adenosine, a well-known immunomodulator influencing inflammatory processes.
Evaluation of the Carba NP Test for Rapid Detection of Carbapenemase-Producing Enterobacteriaceae and Pseudomonas aeruginosa
Authors: Tijet Nathalie , Boyd David , Patel Samir N. , Mulvey Michael R. , Melano Roberto G. 
Published: July 2013

ABSTRACT

The Carba NP test was evaluated against a panel of 244 carbapenemase- and non-carbapenemase-producing
Enterobacteriaceae
and
Pseudomonas aeruginosa
isolates. We confirmed the 100% specificity and positive predictive value of the test, but the sensitivity and negative predictive value were 72.5% and 69.2%, respectively, and increased to 80% and 77.3%, respectively, using a more concentrated bacterial extract. False-negative results were associated with mucoid strains or linked to enzymes with low carbapenemase activity, particularly OXA-48-like, which has emerged globally in enterobacteria.
MntABC and MntH Contribute to Systemic Staphylococcus aureus Infection by Competing with Calprotectin for Nutrient Manganese
Authors: Kehl-Fie Thomas E. , Zhang Yaofang , Moore Jessica L. , Farrand Allison J. , Hood M. Indriati , Rathi Subodh , Chazin Walter J. , Caprioli Richard M. , Skaar Eric P. 
Published: July 2013

ABSTRACT

During infection, vertebrates limit access to manganese and zinc, starving invading pathogens, such as
Staphylococcus aureus
, of these essential metals in a process termed “nutritional immunity.” The manganese and zinc binding protein calprotectin is a key component of the nutrient-withholding response, and mice lacking this protein do not sequester manganese from
S. aureus
liver abscesses. One potential mechanism utilized by
S. aureus
to minimize host-imposed manganese and zinc starvation is the expression of the metal transporters MntABC and MntH. We performed transcriptional analyses of both
mntA
and
mntH
, which revealed increased expression of both systems in response to calprotectin treatment. MntABC and MntH compete with calprotectin for manganese, which enables
S. aureus
growth and retention of manganese-dependent superoxide dismutase activity. Loss of MntABC and MntH results in reduced staphylococcal burdens in the livers of wild-type but not calprotectin-deficient mice, suggesting that these systems promote manganese acquisition during infection. During the course of these studies, we observed that metal content and the importance of calprotectin varies between murine organs, and infection leads to profound changes in the anatomical distribution of manganese and zinc. In total, these studies provide insight into the mechanisms utilized by bacteria to evade host-imposed nutrient metal starvation and the critical importance of restricting manganese availability during infection.
Role of the Zinc Uptake ABC Transporter of Moraxella catarrhalis in Persistence in the Respiratory Tract
Authors: Murphy Timothy F. , Brauer Aimee L. , Kirkham Charmaine , Johnson Antoinette , Koszelak-Rosenblum Mary , Malkowski Michael G. 
Published: July 2013

ABSTRACT

Moraxella catarrhalis
is a human respiratory tract pathogen that causes otitis media in children and lower respiratory tract infections in adults with chronic obstructive pulmonary disease. We have identified and characterized a zinc uptake ABC transporter that is present in all strains of
M. catarrhalis
tested. A mutant in which the
znu
gene cluster is knocked out shows markedly impaired growth compared to the wild type in medium that contains trace zinc; growth is restored to wild-type levels by supplementing medium with zinc but not with other divalent cations. Thermal-shift assays showed that the purified recombinant substrate binding protein ZnuA binds zinc but does not bind other divalent cations. Invasion assays with human respiratory epithelial cells demonstrated that the zinc ABC transporter of
M. catarrhalis
is critical for invasion of respiratory epithelial cells, an observation that is especially relevant because an intracellular reservoir of
M. catarrhalis
is present in the human respiratory tract and this reservoir is important for persistence. The
znu
knockout mutant showed marked impairment in its capacity to persist in the respiratory tract compared to the wild type in a mouse pulmonary clearance model. We conclude that the zinc uptake ABC transporter mediates uptake of zinc in environments with very low zinc concentrations and is critical for full virulence of
M. catarrhalis
in the respiratory tract in facilitating intracellular invasion of epithelial cells and persistence in the respiratory tract.
To remove or to replace traditional electronic games? A crossover randomised controlled trial on the impact of removing or replacing home access to electronic games on physical activity and sedentary behaviour in children aged 10–12 years
Authors: Straker Leon M , Abbott Rebecca A , Smith Anne J 
Published: July 2013

ObjectiveTo evaluate the impact of (1) the removal of home access to traditional electronic games or (2) their replacement with active input electronic games, on daily physical activity and sedentary behaviour in children aged 10–12 years.DesignCrossover randomised controlled trial, over 6 months.SettingFamily homes in metropolitan Perth, Australia from 2007 to 2010.Participants10-year-old to 12-year-old children were recruited through school and community media. From 210 children who were eligible, 74 met inclusion criteria, 8 withdrew and 10 had insufficient primary outcome measures, leaving 56 children (29 female) for analysis.InterventionA counterbalanced randomised order of three conditions sustained for 8 weeks each: no home access to electronic games, home access to traditional electronic games and home access to active input electronic games.Main outcome measuresPrimary outcome was accelerometer assessed moderate/vigorous physical activity (MVPA). Secondary outcomes included sedentary time and diary assessed physical activity and sedentary behaviours.ResultsDaily MVPA across the whole week was not significantly different between conditions. However, compared with home access to traditional electronic games, removal of all electronic games resulted in a significant increase in MVPA (mean 3.8 min/day, 95% CI 1.5 to 6.1) and a decrease in sedentary time (4.7 min/day, 0.0 to 9.5) in the after-school period. Similarly, replacing traditional games with active input games resulted in a significant increase in MVPA (3.2 min/day, 0.9 to 5.5) and a decrease in sedentary time (6.2 min/day, 1.4 to 11.4) in the after-school period. Diary reports supported an increase in physical activity and a decrease in screen-based sedentary behaviours with both interventions.ConclusionsRemoval of sedentary electronic games from the child's home and replacing these with active electronic games both resulted in small, objectively measured improvements in after-school activity and sedentary time. Parents can be advised that replacing sedentary electronic games with active electronic games is likely to have the same effect as removing all electronic games.Trial RegistrationAustralia and New Zealand Clinical Trials Registry (ACTRN 12609000279224)
Airborne thermal remote sensing of the Volcán de Colima (Mexico) lava dome from 2007 to 2010
Authors: Hutchison William , Varley Nick , Pyle David M. , Mather Tamsin A. , Stevenson John A. 
Published: July 2013

Abstract
We investigate high-resolution digital photographs and infrared images of the lava dome eruption at Volcán de Colima, from 2007 to 2010. Qualitative observations provide insight into active volcanic processes (e.g. rockfalls and fracturing) and show that, as the dome advances a substantial cooled talus apron develops, which stabilizes the structure. Progressive collapse of the talus apron as it reaches the crater rim corresponds with the development of a lava lobe, extruding hot lava from deeper within the dome. Quantitative dome surface temperature time-series show that the highest temperature hotspots migrate from the dome sides (250–380 °C) to the top (150–300 °C) and finally to the lava lobe (220–400 °C) as the structurally unstable areas expose fresh material. Net surface heat loss from the dome ranges from 5 to 30 MW, comparable to other dome forming systems. Heat budget calculations confirm that the lava dome retained a hot viscous core throughout the period 2007–2010. We propose that the mechanical stability of the Volcán de Colima dome arises from the shear strength of flanking talus which stabilizes the hot viscous core.
Analysis and optimization for boolean expression indexing
Authors: Sadoghi Mohammad , Jacobsen Hans-Arno 
Published: July 2013

BE-Tree is a novel dynamic data structure designed to efficiently index Boolean expressions over a high-dimensional discrete space. BE Tree-copes with both high-dimensionality and expressiveness of Boolean expressions by introducing an effective two-phase space-cutting technique that specifically utilizes the discrete and finite domain properties of the space. Furthermore, BE-Tree employs self-adjustment policies to dynamically adapt the tree as the workload changes. Moreover, in BE-Tree, we develop two novel cache-conscious predicate evaluation techniques, namely, lazy and bitmap evaluations, that also exploit the underlying discrete and finite space to substantially reduce BE-Tree's matching time by up to 75%
BE-Tree is a general index structure for matching Boolean expression which has a wide range of applications including (complex) event processing, publish/subscribe matching, emerging applications in cospaces, profile matching for targeted web advertising, and approximate string matching. Finally, the superiority of BE-Tree is proven through a comprehensive evaluation with state-of-the-art index structures designed for matching Boolean expressions.
Pushing CDN-ISP collaboration to the limit
Authors: Frank Benjamin , Poese Ingmar , Lin Yin , Smaragdakis Georgios , Feldmann Anja , Maggs Bruce , Rake Jannis , Uhlig Steve , Weber Rick 
Published: July 2013

Today a spectrum of solutions are available for istributing content over the Internet, ranging from commercial CDNs to ISP-operated CDNs to content-provider-operated CDNs to peer-to-peer CDNs. Some deploy servers in just a few large data centers while others deploy in thousands of locations or even on millions of desktops. Recently, major CDNs have formed strategic alliances with large ISPs to provide content delivery network solutions. Such alliances show the natural evolution of content delivery today driven by the need to address scalability issues and to take advantage of new technology and business opportunities.
In this paper we revisit the design and operating space of CDN-ISP collaboration in light of recent ISP and CDN alliances. We identify two key enablers for supporting collaboration and improving content delivery performance: informed end-user to server assignment and in-network server allocation. We report on the design and evaluation of a prototype system, NetPaaS, that materializes them. Relying on traces from the largest commercial CDN and a large tier-1 ISP, we show that NetPaaS is able to increase CDN capacity on-demand, enable coordination, reduce download time, and achieve multiple traffic engineering goals leading to a win-win situation for both ISP and CDN.
Strengthening measurements from the edges
Authors: Basso Simone , Meo Michela , De Martin Juan Carlos 
Published: July 2013

Network users know much less than ISPs, Internet exchanges and content providers about what happens inside the network. Consequently users cannot either easily detect network neutrality violations or readily exercise their market power by knowledgeably switching ISPs.
This paper contributes to the ongoing efforts to empower users by proposing two models to estimate -- via application-level measurements -- a key network indicator, i.e., the packet loss rate (PLR) experienced by FTP-like TCP downloads.
Controlled, testbed, and large-scale experiments show that the Inverse Mathis model is simpler and more consistent across the whole PLR range, but less accurate than the more advanced Likely Rexmit model for landline connections and moderate PLR.