bluuebunny/crossref_metadata_2025_split huggingface dataset:
Specificity and transcriptional activity of microbiota associated with low and high microbial abundance sponges from the Red Sea
Authors: Moitinho‐Silva Lucas , Bayer Kristina , Cannistraci Carlo V. , Giles Emily C. , Ryu Taewoo , Seridi Loqmane , Ravasi Timothy , Hentschel Ute 
Published: August 2013

AbstractMarine sponges are generally classified as high microbial abundance (HMA) and low microbial abundance (LMA) species. Here, 16S rRNA amplicon sequencing was applied to investigate the diversity, specificity and transcriptional activity of microbes associated with an LMA sponge (Stylissa carteri), an HMA sponge (Xestospongia testudinaria) and sea water collected from the central Saudi Arabia coast of the Red Sea. Altogether, 887 068 denoised sequences were obtained, of which 806 661 sequences remained after quality control. This resulted in 1477 operational taxonomic units (OTUs) that were assigned to 27 microbial phyla. The microbial composition of S. carteri was more similar to that of sea water than to that of X. testudinaria, which is consistent with the observation that the sequence data set of S. carteri contained many more possibly sea water sequences (~24%) than the X. testudinaria data set (~6%). The most abundant OTUs were shared between all three sources (S. carteri, X. testudinaria, sea water), while rare OTUs were unique to any given source. Despite this high degree of overlap, each sponge species contained its own specific microbiota. The X. testudinaria‐specific bacterial taxa were similar to those already described for this species. A set of S. carteri‐specific bacterial taxa related to Proteobacteria and Nitrospira was identified, which are likely permanently associated with S. carteri. The transcriptional activity of sponge‐associated microorganisms correlated well with their abundance. Quantitative PCR revealed the presence of Poribacteria, representing typical sponge symbionts, in both sponge species and in sea water; however, low transcriptional activity in sea water suggested that Poribacteria are not active outside the host context.
Variation at phenological candidate genes correlates with timing of dispersal and plumage morph in a sedentary bird of prey
Authors: Chakarov Nayden , Jonker Rudy M. , Boerner Martina , Hoffman Joseph I. , Krüger Oliver 
Published: August 2013

AbstractPolymorphic genes involved in the conserved molecular signalling of circadian and circannual clocks may play important roles in governing the timing of breeding and dispersal and thereby affect fitness in vertebrates. However, relatively few studies have explored associations between phenological candidate genes and behaviour, and these are somewhat biased towards particular taxonomic groups such as passerine birds and salmonid fish. Consequently, we assayed microsatellite polymorphisms within the exonic and 3′ untranslated regions of the regulatory genes CLOCK, NPAS2, ADCYAP1 and CREB1 in the common buzzard (Buteo buteo), a polymorphic raptor species with three plumage morphs that differ in key life history traits including lifetime reproductive success. In contrast to studies of passerines, CLOCK poly‐glutamine (poly‐Q) was found to be monomorphic in 976 common buzzard nestlings as well as in three other Buteo species. Moreover, none of the candidate genes were significantly associated with fledging dates, although intermediately melanized females were found to lay earlier on average than light or dark morph individuals, and their offspring carried longer ADCYAP1 alleles. In contrast, all three candidate genes explained significant variation in one or more measures of juvenile buzzard dispersal (resighting probability, timing of dispersal and distance dispersed). Our findings contribute towards a broader body of work on the adaptive significance of CLOCK polymorphism, while also building upon previous studies that have documented links between ADCYAP1 variability and the timing of migration.
Speciation in fishes
Authors: Bernardi Giacomo 
Published: August 2013

AbstractThe field of speciation has seen much renewed interest in the past few years, with theoretical and empirical advances that have moved it from a descriptive field to a predictive and testable one. The goal of this review is to provide a general background on research on speciation as it pertains to fishes. Three major components to the question are first discussed: the spatial, ecological and sexual factors that influence speciation mechanisms. We then move to the latest developments in the field of speciation genomics. Affordable and rapidly available, massively parallel sequencing data allow speciation studies to converge into a single comprehensive line of investigation, where the focus has shifted to the search for speciation genes and genomic islands of speciation. We argue that fish present a very diverse array of scenarios, making them an ideal model to study speciation processes.
Contribution of Hydrogen Sulfide to the Control of Coronary Blood Flow
Authors: Casalini Eli D. , Goodwill Adam G. , Owen Meredith K. , Moberly Steven P. , Berwick Zachary C. , Tune Johnathan D. 
Published: August 2013

AbstractObjectiveThis study examined the mechanisms by which H2S modulates coronary microvascular resistance and myocardial perfusion at rest and in response to cardiac ischemia.MethodsExperiments were conducted in isolated coronary arteries and in open‐chest anesthetized dogs.ResultsWe found that the H2S substrate l‐cysteine (1–10 mM) did not alter coronary tone of isolated arteries in vitro or coronary blood flow in vivo. In contrast, intracoronary (ic) H2S (0.1–3 mM) increased coronary flow from 0.49 ± 0.08 to 2.65 ± 0.13 mL/min/g (p < 0.001). This increase in flow was unaffected by inhibition of Kv channels with 4‐aminopyridine (p = 0.127) but was attenuated (0.23 ± 0.02–1.13 ± 0.13 mL/min/g) by the KATP channel antagonist glibenclamide (p < 0.001). Inhibition of NO synthesis (l‐NAME) did not attenuate coronary responses to H2S. Immunohistochemistry revealed expression of CSE, an endogenous H2S enzyme, in myocardium. Inhibition of CSE with β‐cyano‐l‐alanine (10 μM) had no effect on baseline coronary flow or responses to a 15‐second coronary occlusion (p = 0.82).ConclusionsThese findings demonstrate that exogenous H2S induces potent, endothelial‐independent dilation of the coronary microcirculation predominantly through the activation of KATP channels, however, our data do not support a functional role for endogenous H2S in the regulation of coronary microvascular resistance.
Virulence in Pectobacterium atrosepticum is regulated by a coincidence circuit involving quorum sensing and the stress alarmone, (p)ppGpp
Authors: Bowden Steven D. , Eyres Alison , Chung Jade C. S. , Monson Rita E. , Thompson Arthur , Salmond George P. C. , Spring David R. , Welch Martin 
Published: August 2013

SummaryPectobacterium atrosepticum (Pca) is a Gram‐negative phytopathogen which causes disease by secreting plant cell wall degrading exoenzymes (PCWDEs). Previous studies have shown that PCWDE production is regulated by (i) the intercellular quorum sensing (QS) signal molecule, 3‐oxo‐hexanoyl‐l‐homoserine lactone (OHHL), and (ii) the intracellular ‘alarmone’, (p)ppGpp, which reports on nutrient limitation. Here we show that these two signals form an integrated coincidence circuit which ensures that metabolically costly PCWDE synthesis does not occur unless the population is simultaneously quorate and nutrient limited. A (p)ppGpp null ΔrelAΔspoT mutant was defective in both OHHL and PCWDE production, and nutritional supplementation of wild type cultures (which suppresses (p)ppGpp production) also suppressed OHHL and PCWDE production. There was a substantial overlap in the transcriptome of a (p)ppGpp deficient relA mutant and of a QS defective expI (OHHL synthase) mutant, especially with regards to virulence‐associated genes. Random transposon mutagenesis revealed that disruption of rsmA was sufficient to restore PCWDE production in the (p)ppGpp null strain. We found that the ratio of RsmA protein to its RNA antagonist, rsmB, was modulated independently by (p)ppGpp and QS. While QS predominantly controlled virulence by modulating RsmA levels, (p)ppGpp exerted regulation through the modulation of the RsmA antagonist, rsmB.
Ontogeny, morphology and taxonomy of the soft‐bodied Cambrian ‘mollusc’ Wiwaxia
Authors: Smith Martin R. 
Published: August 2013

AbstractThe soft‐bodied Cambrian organism Wiwaxia poses a taxonomic conundrum. Its imbricated dorsal scleritome suggests a relationship with the polychaete annelid worms, whereas its mouthparts and naked ventral surface invite comparison with the molluscan radula and foot. 476 new and existing specimens from the 505‐Myr‐old Burgess Shale cast fresh light on Wiwaxia's sclerites and scleritome. My observations illuminate the diversity within the genus and demonstrate that Wiwaxia did not undergo discrete moult stages; rather, its scleritome developed gradually, with piecewise addition and replacement of individually secreted sclerites. I recognize a digestive tract and creeping foot in Wiwaxia, solidifying its relationship with the contemporary Odontogriphus. Similarities between the scleritomes of Wiwaxia, halkieriids, Polyplacophora and Aplacophora hint that the taxa are related. A molluscan affinity is robustly established, and Wiwaxia provides a good fossil proxy for the ancestral aculiferan – and perhaps molluscan – body plan.
Parsing Macpherson: The Last Rites of Locke the Possessive Individualist
Authors: Breakey Hugh 
Published: August 2013

AbstractC.B. Macpherson's “Possessive Individualist” reading of Locke is one of the most radical and influential interpretations in the history of exegesis. Despite a substantial critical response over the past five decades, Macpherson's reading remains orthodox in various circles in the humanities generally, particularly in legal studies, and his interpretation of several crucial passages has unwittingly been followed even by his sharpest critics within Lockean scholarship. In order to present the definitive rebuttal to this interpretation, and so finally to lay it to rest, I argue that every one of Macpherson's key pieces of textual evidence can be rejected entirely on its own terms; that is, by reference to no more than its immediate context. In this way I contend that fault of the Possessive Individualist reading lies far deeper than mere cherry‐picking of the Lockean corpus, but centrally involves misreading, misplacing and misrepresenting the very parts of Locke's work Macpherson cites as evidence for his reading.
Russell and Wittgenstein on Logical Form and Judgement: What did Wittgenstein Try that Wouldn't Work?
Authors: Connelly James 
Published: August 2013

AbstractIn this article, I pay special expository attention to two pieces of philosophically relevant Wittgenstein–Russell correspondence from the period leading up to the ultimate demise of Russell's Theory of Knowledge manuscript (in June 1913). This is done in the hopes of shedding light on Wittgenstein's notoriously obscure criticisms of Russell's multiple relation theory of judgement. I argue that these two pieces of correspondence (the first, a letter from Wittgenstein to Russell dated January 1913, and the second, a letter from Russell to Ottoline Morrell, reporting a tense confrontation with Wittgenstein on 26 May 1913) each refer to what is more or less the same approach to problems concerning the unity and well‐formedness of propositions or judgements. However, the view advanced in Wittgenstein's January letter to Russell nevertheless differs in a key respect from the view of Russell's referred to in the May letter to Morrell. The difference involves Wittgenstein's incorporating qualities and relations as unsaturated parts of the copulae of atomic complexes, where these copulae are in turn conceived as logical forms. Because such an approach to logical form (and more specifically, to relations) was philosophically unpalatable to Russell, he undertook an alternative theoretical correction in the context of his 1913 Theory of Knowledge manuscript. This theoretical correction was discussed with Wittgenstein during the tense confrontation on 26 May, and involved deploying a supplemental significance constraint on judgements. It was this significance constraint on judgements, moreover, which was the ‘premiss’ alluded to by Wittgenstein in the context of a June 1913 letter to Russell, wherein he claims to express his objection to Russell's theory ‘exactly.’
Oral DAV131, a Charcoal-Based Adsorbent, Inhibits Intestinal Colonization by β-Lactam-Resistant Klebsiella pneumoniae in Cefotaxime-Treated Mice
Authors: Grall Nathalie , Massias Laurent , Nguyen Thu Thuy , Sayah-Jeanne Sakina , Ducrot Nicolas , Chachaty Elisabeth , de Gunzburg Jean , Andremont Antoine 
Published: August 2013

ABSTRACT

Antibiotics excreted into the intestinal tract, such as broad-spectrum cephalosporins, disrupt the indigenous microflora, affect colonization resistance (CR), and promote intestinal colonization by resistant bacteria. We tested whether oral DAV131, a charcoal-based adsorbent, would prevent colonization by a cefotaxime (CTX)-resistant
Klebsiella pneumoniae
strain (PUG-2) in CTX-treated mice. Mice received CTX, saline, CTX and DAV131, or saline and DAV131 for 3 days before oral challenge with 10
6
CFU of PUG-2. The fecal CTX concentrations and counts of PUG-2 were assayed. Fecal CTX disappeared when DAV131 was given concomitantly with CTX (
P
< 0.05), and the area under the curve of PUG-2 fecal density was significantly reduced (
P
< 0.01). In conclusion, reducing intestinal antibiotic exposure with DAV131 may reduce colonization by resistant strains during treatment compared to treatment with CTX only. This might open new possibilities for decreasing the impact of antibiotics on the intestinal microbiota during treatments.
Molecular Resistance Mechanisms of Macrolide-Resistant Invasive Streptococcus pneumoniae Isolates from Alaska, 1986 to 2010
Authors: Rudolph Karen , Bulkow Lisa , Bruce Michael , Zulz Tammy , Reasonover Alisa , Harker-Jones Marcella , Hurlburt Debby , Hennessy Thomas 
Published: August 2013

ABSTRACT

The rapid emergence of antibiotic-resistant pneumococcal strains has reduced treatment options. The aim of this study was to determine antimicrobial susceptibilities, serotype distributions, and molecular resistance mechanisms among macrolide-resistant invasive pneumococcal isolates in Alaska from 1986 to 2010. We identified cases of invasive pneumococcal disease in Alaska from 1986 to 2010 through statewide population-based laboratory surveillance. All invasive pneumococcal isolates submitted to the Arctic Investigations Program laboratory were confirmed by standard microbiological methods and serotyped by slide agglutination and the Quellung reaction. MICs were determined by the broth microdilution method, and macrolide-resistant genotypes were determined by multiplex PCR. Among 2,923 invasive pneumococcal isolates recovered from 1986 to 2010, 270 (9.2%) were nonsusceptible to erythromycin; 177 (66%) erythromycin-nonsusceptible isolates demonstrated coresistance to penicillin, and 167 (62%) were multidrug resistant. The most frequent serotypes among the macrolide-resistant isolates were serotypes 6B (23.3%), 14 (20.7%), 19A (16.7%), 9V (8.9%), 19F (6.3%), 6A (5.6%), and 23F (4.8%).
mef
and
erm
(B) genes were detected in 207 (77%) and 32 (12%) of the isolates, respectively. Nineteen (7%) of the erythromycin-nonsusceptible isolates contained both
mef
and
erm
(B) genotypes; 15 were of serotype 19A. There was significant year-to-year variation in the proportion of isolates that were nonsusceptible to erythromycin (
P
< 0.001). Macrolide resistance among pneumococcal isolates from Alaska is mediated predominantly by
mef
genes, and this has not changed significantly over time. However, there was a statistically significant increase in the proportion of isolates that possess both
erm
(B) and
mef
, primarily due to serotype 19A isolates.
Kallistatin Modulates Immune Cells and Confers Anti-Inflammatory Response To Protect Mice from Group A Streptococcal Infection
Authors: Lu Shiou-Ling , Tsai Chiau-Yuang , Luo Yueh-Hsia , Kuo Chih-Feng , Lin Wei-Chieh , Chang Yu-Tzu , Wu Jiunn-Jong , Chuang Woei-Jer , Liu Ching-Chuan , Chao Lee , Chao Julie , Lin Yee-Shin 
Published: August 2013

ABSTRACT
Group A streptococcus (GAS) infection may cause severe life-threatening diseases, including necrotizing fasciitis and streptococcal toxic shock syndrome. Despite the availability of effective antimicrobial agents, there has been a worldwide increase in the incidence of invasive GAS infection. Kallistatin (KS), originally found to be a tissue kallikrein-binding protein, has recently been shown to possess anti-inflammatory properties. However, its efficacy in microbial infection has not been explored. In this study, we transiently expressed the human KS gene by hydrodynamic injection and investigated its anti-inflammatory and protective effects in mice via air pouch inoculation of GAS. The results showed that KS significantly increased the survival rate of GAS-infected mice. KS treatment reduced local skin damage and bacterial counts compared with those in mice infected with GAS and treated with a control plasmid or saline. While there was a decrease in immune cell infiltration of the local infection site, cell viability and antimicrobial factors such as reactive oxygen species actually increased after KS treatment. The efficiency of intracellular bacterial killing in neutrophils was directly enhanced by KS administration. Several inflammatory cytokines, including tumor necrosis factor alpha, interleukin 1β, and interleukin 6, in local infection sites were reduced by KS. In addition, KS treatment reduced vessel leakage, bacteremia, and liver damage after local infection. Therefore, our study demonstrates that KS provides protection in GAS-infected mice by enhancing bacterial clearance, as well as reducing inflammatory responses and organ damage.
Fosfomycin and Tobramycin in Combination Downregulate Nitrate Reductase Genes
narG
and
narH
, Resulting in Increased Activity against Pseudomonas aeruginosa under Anaerobic Conditions
Authors: McCaughey Gerard , Gilpin Deirdre F. , Schneiders Thamarai , Hoffman Lucas R. , McKevitt Matt , Elborn J. Stuart , Tunney Michael M. 
Published: August 2013

ABSTRACT

The activity of aminoglycosides, which are used to treat
Pseudomonas aeruginosa
respiratory infection in cystic fibrosis (CF) patients, is reduced under the anaerobic conditions that reflect the CF lung
in vivo
. In contrast, a 4:1 (wt/wt) combination of fosfomycin and tobramycin (F:T), which is under investigation for use in the treatment of CF lung infection, has increased activity against
P. aeruginosa
under anaerobic conditions. The aim of this study was to elucidate the mechanisms underlying the increased activity of F:T under anaerobic conditions. Microarray analysis was used to identify the transcriptional basis of increased F:T activity under anaerobic conditions, and key findings were confirmed by microbiological tests, including nitrate utilization assays, growth curves, and susceptibility testing. Notably, growth in subinhibitory concentrations of F:T, but not tobramycin or fosfomycin alone, significantly downregulated (
P
< 0.05) nitrate reductase genes
narG
and
narH
, which are essential for normal anaerobic growth of
P. aeruginosa
. Under anaerobic conditions, F:T significantly decreased (
P
< 0.001) nitrate utilization in
P. aeruginosa
strains PAO1, PA14, and PA14
lasR
::Gm, a mutant known to exhibit increased nitrate utilization. A similar effect was observed with two clinical
P. aeruginosa
isolates. Growth curves indicate that nitrate reductase transposon mutants had reduced growth under anaerobic conditions, with these mutants also having increased susceptibility to F:T compared to the wild type under similar conditions. The results of this study suggest that downregulation of nitrate reductase genes resulting in reduced nitrate utilization is the mechanism underlying the increased activity of F:T under anaerobic conditions.
Impact of
In Vivo
Triazole and Echinocandin Combination Therapy for Invasive Pulmonary Aspergillosis: Enhanced Efficacy against
Cyp51
Mutant Isolates
Authors: Lepak Alexander J. , Marchillo Karen , VanHecker Jamie , Andes David R. 
Published: August 2013

ABSTRACT

Previous studies examining combination therapy for invasive pulmonary aspergillosis (IPA) have revealed conflicting results, including antagonism, indifference, and enhanced effects. The most commonly employed combination for this infection includes a mold-active triazole and echinocandin. Few studies have evaluated combination therapy from a pharmacodynamic (PD) perspective, and even fewer have examined combination therapy against both wild-type and azole-resistant
Cyp51
mutant isolates. The current studies aim to fill this gap in knowledge. Four
Aspergillus fumigatus
isolates were utilized, including a wild-type strain, an
Fks1
mutant (posaconazole susceptible and caspofungin resistant), and two
Cyp51
mutants (posaconazole resistant). A neutropenic murine model of IPA was used for the treatment studies. The dosing design included monotherapy with posaconazole, monotherapy with caspofungin, and combination therapy with both. Efficacy was determined using quantitative PCR, and results were normalized to known quantities of conidia (conidial equivalents [CE]). The static dose, 1-log kill dose, and associated PD target area under the curve (AUC)/MIC ratio were determined for monotherapy and combination therapy. Monotherapy experiments revealed potent activity for posaconazole, with reductions of 3 to 4 log
10
Aspergillus
CE/ml with the two “low”-MIC isolates. Posaconazole alone was less effective for the two isolates with higher MICs. Caspofungin monotherapy did not produce a significant decrease in fungal burden for any strain. Combination therapy with the two antifungals did not enhance efficacy for the two posaconazole-susceptible isolates. However, the drug combination produced synergistic activity against both posaconazole-resistant isolates. Specifically, the combination resulted in a 1- to 2-log
10
decline in burden that would not have been predicted based on the monotherapy results for each drug. This corresponded to a reduction in the free-drug posaconazole AUC/MIC ratio needed for stasis of up to 17-fold. The data suggest that combination therapy using a triazole and an echinocandin may be a beneficial treatment strategy for triazole-resistant isolates.
Clinical Pharmacodynamic Index Identification for Micafungin in Esophageal Candidiasis: Dosing Strategy Optimization
Authors: Andes David R. , Reynolds Daniel K. , Van Wart Scott A. , Lepak Alexander J. , Kovanda Laura L. , Bhavnani Sujata M. 
Published: August 2013

ABSTRACT

Echinocandins exhibit concentration-dependent effects on
Candida
species, and preclinical studies support the administration of large, infrequent doses. The current report examines the pharmacokinetics/pharmacodynamics of two multicenter, randomized trials of micafungin dosing regimens that differed in both dose level and dosing interval. Analysis demonstrates the clinical relevance of the dose level and area under the concentration-time curve (AUC). Better, although not statistically significant (
P
= 0.056), outcomes were seen with higher maximum concentrations of drug in serum (
C
max
) and large, infrequent doses. The results support further clinical investigation of novel micafungin dosing regimens with large doses but less than daily administration. (These studies have been registered at ClinicalTrials.gov under registration no. NCT00666185 and NCT00665639.)