bluuebunny/crossref_metadata_2025_split huggingface dataset:
On the rapidity of antibiotic resistance evolution facilitated by a concentration gradient
Authors: Hermsen Rutger , Deris J. Barrett , Hwa Terence 
Published: June 2012

The rapid emergence of bacterial strains resistant to multiple antibiotics is posing a growing public health risk. The mechanisms underlying the rapid evolution of drug resistance are, however, poorly understood. The heterogeneity of the environments in which bacteria encounter antibiotic drugs could play an important role. E.g., in the highly compartmentalized human body, drug levels can vary substantially between different organs and tissues. It has been proposed that this could facilitate the selection of resistant mutants, and recent experiments support this. To study the role of spatial heterogeneity in the evolution of drug resistance, we present a quantitative model describing an environment subdivided into relatively isolated compartments with various antibiotic concentrations, in which bacteria evolve under the stochastic processes of proliferation, migration, mutation and death. Analytical and numerical results demonstrate that concentration gradients can foster a mode of adaptation that is impossible in uniform environments. It allows resistant mutants to evade competition and circumvent the slow process of fixation by invading compartments with higher drug concentrations, where less resistant strains cannot subsist. The speed of this process increases sharply with the sensitivity of the growth rate to the antibiotic concentration, which we argue to be generic. Comparable adaptation rates in uniform environments would require a high selection coefficient (
s
> 0.1) for each forward mutation. Similar processes can occur if the heterogeneity is more complex than just a linear gradient. The model may also be applicable to other adaptive processes involving environmental heterogeneity and range expansion.
Theory of active transport in filopodia and stereocilia
Authors: Zhuravlev Pavel I. , Lan Yueheng , Minakova Maria S. , Papoian Garegin A. 
Published: June 2012

The biological processes in elongated organelles of living cells are often regulated by molecular motor transport. We determined spatial distributions of motors in such organelles, corresponding to a basic scenario when motors only walk along the substrate, bind, unbind, and diffuse. We developed a mean-field model, which quantitatively reproduces elaborate stochastic simulation results as well as provides a physical interpretation of experimentally observed distributions of Myosin IIIa in stereocilia and filopodia. The mean-field model showed that the jamming of the walking motors is conspicuous, and therefore damps the active motor flux. However, when the motor distributions are coupled to the delivery of actin monomers toward the tip, even the concentration bump of G actin that they create before they jam is enough to speed up the diffusion to allow for severalfold longer filopodia. We found that the concentration profile of G actin along the filopodium is rather nontrivial, containing a narrow minimum near the base followed by a broad maximum. For efficient enough actin transport, this nonmonotonous shape is expected to occur under a broad set of conditions. We also find that the stationary motor distribution is universal for the given set of model parameters regardless of the organelle length, which follows from the form of the kinetic equations and the boundary conditions.
Structure/function correlations among coupled binuclear copper proteins through spectroscopic and reactivity studies of NspF
Authors: Ginsbach Jake W. , Kieber-Emmons Matthew T. , Nomoto Ryohei , Noguchi Akio , Ohnishi Yasuo , Solomon Edward I. 
Published: June 2012

The terminal step of 4-hydroxy-3-nitrosobenzamide biosynthesis in
Streptomyces murayamaensis
is performed by NspF, a mono-oxygenase that converts
o
-aminophenols to the corresponding nitroso product (hydroxyanilinase activity). Previous biochemical characterization of the resting form of NspF suggested that this enzyme belonged to the coupled binuclear copper enzyme (CBC) family. Another member of this enzyme family, tyrosinase, is able to mono-oxygenate monophenols (monophenolase activity) but not
o
-aminophenols. To gain insight into the unique reactivity of NspF, we have generated and characterized the oxy form of its active site. The observation of spectral features identical to those of oxy-tyrosinase indicates that oxy-NspF contains a Cu
2
O
2
core where peroxide is coordinated in a
μ
-
η
2
∶
η
2
mode, confirming that NspF is a CBC enzyme. This oxy form is found to react with monophenols, indicating that, like tyrosinase, NspF also possesses monophenolase activity. A comparison of the two electrophilic mechanisms for the monophenolase and hydroxyanilinase activity indicates a large geometric change between their respective transition states. The potential for specific interactions between the protein pocket and the substrate in each transition state is discussed within the context of the differential reactivity of this family of enzymes with equivalent
μ
-
η
2
∶
η
2
peroxy bridged coupled binuclear copper active sites.
Low-Elevation Dams Are Impediments to Adult Pacific Lamprey Spawning Migration in the Umatilla River, Oregon
Authors: Jackson Aaron , Moser Mary 
Published: June 2012

Abstract
Due to tribal concerns over the recent decline of Pacific lamprey Lampetra tridentata, a restoration program was initiated to establish a self-sustaining, harvestable lamprey population within the ceded lands of the Confederated Tribes of the Umatilla Indian Reservation in Oregon. We hypothesized that low returns of adult lampreys to spawning areas in the Umatilla River were caused by loss of habitat connectivity in this watershed. We conducted a study to determine whether the ubiquitous, low-elevation irrigation diversion dams in the main-stem Umatilla River were obstacles to adult lamprey spawning migration. Radiotelemetry was used to assess lamprey passage efficiency at seven dams located within the lowest 55-km reach of the Umatilla River. During this 4-year study, we tracked 217 adult Pacific lampreys that were implanted with radio transmitters and released downstream from the dams. Logistic regression analysis indicated that dam design, fish size, and temperature had the greatest effects on passage efficiency. Poor performance (&lt;30% fitted passage probability) was recorded at the two lowest dams in the system and resulted in limited escapement to upper sites. During the study, one dam was breached, after which passage efficiency there immediately improved from 32% to 81%. In addition, water augmentation actions at Three Mile Falls Dam apparently contributed to improved mean passage efficiency of migratory-phase fish (from 17% to 50%). Thus, actions to improve adult lamprey access to historical spawning areas are feasible and are key to successful restoration of this species.
Received June 29, 2011; accepted February 13, 2012
Effect of Brook Trout Removal from a Spawning Stream on an Adfluvial Population of Lahontan Cutthroat Trout
Authors: Scoppettone G. Gary , Rissler Peter H. , Shea Sean P. , Somer William 
Published: June 2012

Abstract
Independence Lake (Nevada and Sierra counties, California) harbors the only extant native population of Lahontan cutthroat trout Oncorhynchus clarkii henshawi in the Truckee River system and one of two extant adfluvial populations in the Lahontan basin. The persistence of this population has been precarious for more than 50 years, with spawning runs consisting of only 30–150 fish. It is assumed that this population was much larger prior to the introduction of nonnative brook trout Salvelinus fontinalis. Brook trout overlap with cutthroat trout in upper Independence Creek, where the cutthroat trout spawn and their resulting progeny emigrate to Independence Lake. In 2005, we began removing brook trout from upper Independence Creek using electrofishers and monitored the cutthroat trout population. Stomach analysis of captured brook trout revealed cutthroat trout fry, and cutthroat trout fry survival increased significantly from 4% to 12% with brook trout removal. Prior to brook trout removal, the only Lahontan cutthroat trout progeny emigrating to Independence Lake were fry; with brook trout removal, juveniles were found entering the lake. In 2010, 237 potential spawners passed a prefabricated weir upstream of Independence Lake. Although the results of this study suggest that brook trout removal from upper Independence Creek has had a positive influence on the population dynamics of Independence Lake Lahontan cutthroat trout, additional years of removal are needed to assess the ultimate effect this action will have upon the cutthroat trout population.
Received August 26, 2011; accepted February 29, 2012
Effects of sputter-deposition-induced and post-deposition thermally activated intermixing on the exchange bias properties of [Pt/Co]×3/(Pt)/IrMn films
Authors: Letellier F , Baltz V , Lechevallier L , Lardé R , Jacquot J-F , Rodmacq B , Breton J-M Le , Dieny B 
Published: June 2012

Abstract
The effects of sputter-deposition-induced and post-deposition thermally activated layer intermixing on the exchange bias properties of [Pt/Co]
x3/Pt(t
Pt)/IrMn films with out-of-plane anisotropy and deposited under a perpendicular magnetic field are investigated. The consequences of the intermixing on the magnetic properties are correlated with atom probe structural investigations. We observe that Co–Mn and Co–Pt intermixing are already present in the as-deposited state. The intermixing is more pronounced for Pt on Co (∼50%) than for Mn on Co (∼10%). It is observed that annealing up to 200 °C does not result in noticeable further diffusion of Mn in Co. In contrast, it significantly accentuates the Co–Pt initial intermixing. This enhanced intermixing leads to a 40% reduction in the exchange bias field. We measured that this reduction is not primarily due to changes in effective anisotropy or in saturation magnetization. This is possibly ascribed to a decrease in the mean interfacial moment and exchange stiffness both due to the observed reduction in Co content within the Co sublayers.
Bellerophontes: an RNA-Seq data analysis framework for chimeric transcripts discovery based on accurate fusion model
Authors: Abate Francesco , Acquaviva Andrea , Paciello Giulia , Foti Carmelo , Ficarra Elisa , Ferrarini Alberto , Delledonne Massimo , Iacobucci Ilaria , Soverini Simona , Martinelli Giovanni , Macii Enrico 
Published: June 2012

Abstract
Motivation: Next-generation sequencing technology allows the detection of genomic structural variations, novel genes and transcript isoforms from the analysis of high-throughput data. In this work, we propose a new framework for the detection of fusion transcripts through short paired-end reads which integrates splicing-driven alignment and abundance estimation analysis, producing a more accurate set of reads supporting the junction discovery and taking into account also not annotated transcripts. Bellerophontes performs a selection of putative junctions on the basis of a match to an accurate gene fusion model.
Results: We report the fusion genes discovered by the proposed framework on experimentally validated biological samples of chronic myelogenous leukemia (CML) and on public NCBI datasets, for which Bellerophontes is able to detect the exact junction sequence. With respect to state-of-art approaches, Bellerophontes detects the same experimentally validated fusions, however, it is more selective on the total number of detected fusions and provides a more accurate set of spanning reads supporting the junctions. We finally report the fusions involving non-annotated transcripts found in CML samples.
Availability and implementation: Bellerophontes JAVA/Perl/Bash software implementation is free and available at http://eda.polito.it/bellerophontes/.
Contact: francesco.abate@polito.it
Identifying aberrant pathways through integrated analysis of knowledge in pharmacogenomics
Authors: Hoehndorf Robert , Dumontier Michel , Gkoutos Georgios V. 
Published: June 2012

Abstract
Motivation: Many complex diseases are the result of abnormal pathway functions instead of single abnormalities. Disease diagnosis and intervention strategies must target these pathways while minimizing the interference with normal physiological processes. Large-scale identification of disease pathways and chemicals that may be used to perturb them requires the integration of information about drugs, genes, diseases and pathways. This information is currently distributed over several pharmacogenomics databases. An integrated analysis of the information in these databases can reveal disease pathways and facilitate novel biomedical analyses.
Results: We demonstrate how to integrate pharmacogenomics databases through integration of the biomedical ontologies that are used as meta-data in these databases. The additional background knowledge in these ontologies can then be used to enable novel analyses. We identify disease pathways using a novel multi-ontology enrichment analysis over the Human Disease Ontology, and we identify significant associations between chemicals and pathways using an enrichment analysis over a chemical ontology. The drug–pathway and disease–pathway associations are a valuable resource for research in disease and drug mechanisms and can be used to improve computational drug repurposing.
Availability: http://pharmgkb-owl.googlecode.com
Contact: rh497@cam.ac.uk
Debt, Deleveraging, and the Liquidity Trap: A Fisher-Minsky-Koo Approach*
Authors: Eggertsson Gauti B. , Krugman Paul 
Published: June 2012

Abstract
In this article we present a simple new Keynesian–style model of debt-driven slumps—that is, situations in which an overhang of debt on the part of some agents, who are forced into rapid deleveraging, is depressing aggregate demand. Making some agents debt-constrained is a surprisingly powerful assumption. Fisherian debt deflation, the possibility of a liquidity trap, the paradox of thrift and toil, a Keynesian-type multiplier, and a rationale for expansionary fiscal policy all emerge naturally from the model. We argue that this approach sheds considerable light both on current economic difficulties and on historical episodes, including Japan’s lost decade (now in its 18th year) and the Great Depression itself.
Extending Cassava Root Shelf Life via Reduction of Reactive Oxygen Species Production
Authors: Zidenga Tawanda , Leyva-Guerrero Elisa , Moon Hangsik , Siritunga Dimuth , Sayre Richard 
Published: June 2012

Abstract
One of the major constraints facing the large-scale production of cassava (Manihot esculenta) roots is the rapid postharvest physiological deterioration (PPD) that occurs within 72 h following harvest. One of the earliest recognized biochemical events during the initiation of PPD is a rapid burst of reactive oxygen species (ROS) accumulation. We have investigated the source of this oxidative burst to identify possible strategies to limit its extent and to extend cassava root shelf life. We provide evidence for a causal link between cyanogenesis and the onset of the oxidative burst that triggers PPD. By measuring ROS accumulation in transgenic low-cyanogen plants with and without cyanide complementation, we show that PPD is cyanide dependent, presumably resulting from a cyanide-dependent inhibition of respiration. To reduce cyanide-dependent ROS production in cassava root mitochondria, we generated transgenic plants expressing a codon-optimized Arabidopsis (Arabidopsis thaliana) mitochondrial alternative oxidase gene (AOX1A). Unlike cytochrome c oxidase, AOX is cyanide insensitive. Transgenic plants overexpressing AOX exhibited over a 10-fold reduction in ROS accumulation compared with wild-type plants. The reduction in ROS accumulation was associated with a delayed onset of PPD by 14 to 21 d after harvest of greenhouse-grown plants. The delay in PPD in transgenic plants was also observed under field conditions, but with a root biomass yield loss in the highest AOX-expressing lines. These data reveal a mechanism for PPD in cassava based on cyanide-induced oxidative stress as well as PPD control strategies involving inhibition of ROS production or its sequestration.
Revival of Palaeoptera—head characters support a monophyletic origin of Odonata and Ephemeroptera (Insecta)
Authors: Blanke Alexander , Wipfler Benjamin , Letsch Harald , Koch Markus , Beckmann Felix , Beutel Rolf , Misof Bernhard 
Published: June 2012

AbstractThe earliest branching event in winged insects, one of the core problems regarding early insect evolution, was addressed using characters of the head. The head is arguably one of the most complex body regions in insects and the phylogenetic information content of its features has been demonstrated. In contrast, the wings and other body parts related to the flight apparatus and sperm transmission are not useful in the context of this problem, as the outgroups (silverfish and bristletails) are wingless and transmit spermatophores externally. Therefore, they show profound differences in the organization of the postcephalic body, and assessment of homology and subsequent phylogenetic analysis of features of these body regions is extremely difficult. The core of this study is the investigation of head structures of representatives of the major clades of dragonflies. A detailed description of the head of Lestes virens is presented and was used as a starting point for the compilation of a character set and a character state matrix for the entire Dicondylia (winged insects + silverfish), with a main focus on the placement of dragonflies and consequently the basal branching event within winged insects. Our results indicate a sister‐group relationship between a clade Palaeoptera (dragonflies + mayflies) and the megadiverse monophyletic lineage Neoptera. We show that despite considerable structural similarity between the odonate and neopteran mandible, the muscle equipment in dragonflies is more plesiomorphic with respect to Dicondylia than previously known. Odonata and Ephemeroptera also share presumably derived features of the antenna, maxilla, and labial musculature. Parsimony analyses of the head data unambiguously support a clade Palaeoptera.© The Willi Hennig Society 2012.
Male‐killer dynamics inDanaus chrysippus(L.) (Lepidoptera:Nymphalidae) inEastAfrica
Authors: Hassan Sami S. M. , Idris Eihab , Majerus Michael E. N. 
Published: June 2012

AbstractWithin certain regions in East Africa, the butterflyDanaus chrysippus(L.) shows female‐biased population sex ratio, because of the production by some females of all‐female broods, as a result of infection by maternally inherited, male‐killing bacterium of the genusSpiroplasma. In this study, we describe a 3‐year field survey for the population dynamics of the male‐killingSpiroplasmainD. chrysippusin four independent localities, namelyUganda,Ghana,Sudan andMadagascar. The prevalence of the bacterium was found to show extensive variations at multiple scales among different sites, in various countries, seasons and years. A novel, selection‐based hypothesis was suggested to explain the high variability of male‐killer prevalence over space and time, based on the existence of an adaptive link between larval food‐plant density and the magnitude of resource reallocation fitness advantage for the male‐killer.
Low doses of fludrocortisone and hydrocortisone, alone or in combination, on vascular responsiveness to phenylephrine in healthy volunteers
Authors: Laviolle Bruno , Donal Erwan , Le Maguet Pascale , Lainé Fabrice , Bellissant Eric 
Published: June 2012

AimsA single administration of hydrocortisone has been shown to enhance the pressor response to phenylephrine in healthy volunteers and to norepinephrine in septic shock patients. Similar data do not exist for fludrocortisone. Since there continues to be disagreement about the utility of fludrocortisone in septic shock, we assessed the effects of a single administration of low doses of hydrocortisone (50 mg intravenously) and fludrocortisone (50 μg orally), given either alone or in combination, on phenylephrine mean arterial pressure and cardiac systolic and diastolic function dose–response relationships in 12 healthy male volunteers with hypo‐aldosteronism induced by intravenous sodium loading.MethodsThis was a placebo‐controlled, randomized, double‐blind, crossover study performed according to a 2 × 2 factorial design. Subjects received first a 2000 ml infusion of NaCl 0.9% during 2 h. Then fludrocortisone 50 μg (or its placebo) was administered orally and hydrocortisone 50 mg (or its placebo) was injected intravenously. At 1.5 h after treatment administration, incremental doses of phenylephrine were infused (from 0.01 to 3 μg kg−1 min−1), each dose being infused during 5 min.ResultsBoth fludrocortisone (P < 0.001) and hydrocortisone (P = 0.002) induced a significant decrease in pressor response to phenylephrine, their effects being additive (fludrocortisone × hydrocortisone interaction, P = 0.792). The two drugs did not induce any detectable cardiac effect.ConclusionsSingle administrations of fludrocortisone and hydrocortisone decreased the pressor response to phenylephrine in healthy volunteers with hypo‐aldosteronism. These similar effects of hydrocortisone and fludrocortisone probably express a rapid non‐genomic vasodilating effect of the two steroids in the context of acute volume loading.
In papillary thyroid carcinoma BRAFV600E is associated with increased expression of the urokinase plasminogen activator  and its cognate receptor, but not with disease‐free interval
Authors: Ulisse Salvatore , Baldini Enke , Sorrenti Salvatore , Barollo Susi , Prinzi Natalie , Catania Antonio , Nesca Angela , Gnessi Lucio , Pelizzo Maria R. , Mian Caterina , De Vito Corrado , Calvanese Anna , Palermo Silvio , Persechino Severino , De Antoni Enrico , D'Armiento Massimino 
Published: June 2012

SummaryContextIt has been suggested that patients with papillary thyroid cancer (PTC) harbouring the BRAFV600E mutation have a worse prognosis. We showed in PTC that high levels of urokinase plasminogen activator (uPA) and its cognate receptor (uPAR) inversely correlate with disease‐free interval (DFI).ObjectivesTo investigate the effects of BRAFV600E on the expression of uPA and uPAR and to evaluate the prognostic relevance of BRAFV600E alone or in combination with uPA and uPAR.Design/Setting/Patients/InterventionThe case study included 91 patients with PTC. All patients underwent thyroidectomy and radioiodine therapy. Follow‐up was available for 75 patients.Main outcome measuresThe BRAFV600E mutation was analysed by sequencing and mutant allele‐specific PCR amplification; uPA and uPAR expression by quantitative RT‐PCR.ResultsBRAFV600E was found in 44 of the 91 patients and associated with older age, but not with high‐risk clinicopathological features. Urokinase PA and uPAR mRNA levels were higher in tumour tissues by 9·51 ± 1·30 and 4·64 ± 0·44 fold, respectively, compared to normal matched tissues, being significantly higher in BRAFV600E‐positive patients. In vitro induction of BRAFV600E in PCCL3 cells caused a significant increase in both uPA and uPAR mRNAs. Higher levels of uPA and uPAR correlated with lymph node metastases, TNM stage and disease recurrences. Kaplan–Meier and multivariate analyses demonstrated that uPA and uPAR were associated with shorter DFI, while the BRAFV600E was not.ConclusionIn PTC, BRAFV600E induces uPA and uPAR expression. The latter, but not BRAFV600E, associates with advanced stages and shorter DFI. If confirmed in larger case studies, they may represent reliable prognostic markers for more accurate risk stratification and postoperative decision‐making in patients with PTC.