bluuebunny/crossref_metadata_2025 huggingface dataset:
Cooperation between Noncanonical Ras Network Mutations in Cancer
Authors: Stites Edward C , Trampont Paul C , Haney Lisa B , Walk Scott F , Ravichandran Kodi S
Published: May 2014

Cancer develops after the acquisition of a collection of mutations that together create the cancer phenotype. How collections of mutations work together within a cell, and whether there is selection for certain combinations of mutations, are not well understood. Using a Ras signaling network mathematical model we tested potential synergistic combinations within the Ras network. Intriguingly, our modeling, including a computational random mutagenesis approach, and subsequent experiments revealed that mutations of the tumor suppressor gene NF1 can amplify the effects of mutations in multiple other components of the Ras pathway, including weakly activating, noncanonical, Ras mutants. Since conventional wisdom holds that mutations within the same pathway do not co-occur, it was surprising that modeling and experiments both suggested a functional benefit for co-occurring Ras pathway mutations. Furthermore, we analyzed >3900 sequenced cancer specimens from the Cancer Cell Line Encyclopedia (CCLE) and The Cancer Genome Atlas (TCGA) and we uncovered an increased rate of co-occurrence between mutations the model predicted could display synergy. Overall, these data suggest that selective combinations of Ras pathway mutations could serve the role of cancer driver. More generally, this work presents a mechanism by which the context created by one mutation influences the evolutionary trajectories of cancer development, and this work suggests that mutations that result in network instability may promote cancer in a manner analogous to genomic instability.
Genetic dissection of MAPK-mediated complex traits acrossS. cerevisiae
Authors: Treusch Sebastian , Albert Frank W , Bloom Joshua S , Kotenko Iulia E , Kruglyak Leonid
Published: May 2014

Signaling pathways enable cells to sense and respond to their environment. Many cellular signaling strategies are conserved from fungi to humans, yet their activity and phenotypic consequences can vary extensively among individuals within a species. A systematic assessment of the impact of naturally occurring genetic variation on signaling pathways remains to be conducted. InS. cerevisiae, both response and resistance to stressors that activate signaling pathways differ between diverse isolates. Here, we present a quantitative trait locus (QTL) mapping approach that enables us to identify genetic variants underlying such phenotypic differences across the genetic and phenotypic diversity ofS. cerevisiae. Using a Round-robin cross between twelve diverse strains, we determined the genetic architectures of phenotypes critically dependent on MAPK signaling cascades. Genetic variants identified fell within MAPK signaling networks themselves as well as other interconnected signaling pathways, illustrating how genetic variation can shape the phenotypic output of highly conserved signaling cascades.
Stitching together the Multiple Dimensions of Autophagy Using Metabolomics and Transcriptomics Reveals Impacts on Metabolism, Development, and Plant Responses to the Environment inArabidopsis
Authors: Masclaux-Daubresse Céline , Clément Gilles , Anne Pauline , Routaboul Jean-Marc , Guiboileau Anne , Soulay Fabienne , Shirasu Ken , Yoshimoto Kohki
Published: May 2014

Autophagy is a fundamental process in the plant life story, playing a key role in immunity, senescence, nutrient recycling, and adaptation to the environment. Transcriptomics and metabolomics of the rosette leaves of Arabidopsis thaliana autophagy mutants (atg) show that autophagy is essential for cell homeostasis and stress responses and that several metabolic pathways are affected. Depletion of hexoses, quercetins, and anthocyanins parallel the overaccumulation of several amino acids and related compounds, such as glutamate, methionine, glutathione, pipecolate, and 2-aminoadipate. Transcriptomic data show that the pathways for glutathione, methionine, raffinose, galacturonate, and anthocyanin are perturbed. Anthocyanin depletion in atg mutants, which was previously reported as a possible defect in flavonoid trafficking to the vacuole, appears due to the downregulation of the master genes encoding the enzymes and regulatory proteins involved in flavonoid biosynthesis. Overexpression of the PRODUCTION OF ANTHOCYANIN PIGMENT1 transcription factor restores anthocyanin accumulation in vacuoles of atg mutants. Transcriptome analyses reveal connections between autophagy and (1) salicylic acid biosynthesis and response, (2) cytokinin perception, (3) oxidative stress and plant defense, and possible interactions between autophagy and the COP9 signalosome machinery. The metabolic and transcriptomic signatures identified for the autophagy mutants are discussed and show consistencies with the observed phenotypes.
Cs3ScCl6
Authors: Ward Matthew D. , Ibers James A.
Published: May 2014

Crystals of tricaesium scandium(III) hexachloride were obtained as a side product from the reaction of U, SnCl2, Sc, and S in a CsCl flux at 1073 K. Cs3ScCl6crystallizes in the Rb3YCl6structure type. The asymmetric unit comprises three Cs sites, two Sc sites, and six Cl sites, all of which have site symmetry 1, except for the two Sc sites that have site symmetries of 2 and -1, respectively. The structure is composed of isolated [ScCl6]3−octahedra that are surrounded by Cs+cations. Two Cs+cations have interactions with eight Cl−anions, while the third has interactions with ten Cl−anions.
1-[4-Bromo-2-(trifluoromethoxy)phenyl]-3-methyl-1H-1,2,4-triazole
Authors: Sandeep C , Padmashali Basavaraj , Suchetan P. A. , Kulkarni Rashmi S.
Published: May 2014

In the title compound, C10H7BrF3N3O, the dihedral angle between the benzene and triazole rings is 23.17 (12)° and the C atom of the –CF3group deviates from its attached ring plane by 1.147 (3) Å. In the crystal, molecules are linked by C—H...N interactions, generatingC(7) chains running along [010].
Trias of keratosis pilaris, ulerythema ophryogenes and 18p monosomy: Zouboulis syndrome
Authors: Liakou Aikaterini I. , Esteves de Carvalho André V. , Nazarenko Lujdmila P.
Published: May 2014

Keratosis pilaris and ulerythema ophryogenes (keratosis pilaris atrophicans faciei) are part of a group of hereditary disorders of hair follicle keratinization involving follicular inflammation and subsequent atrophy. Monosomy 18p refers to a chromosomal disorder resulting from the deletion of all or part of the short arm of chromosome 18. This trias was first described in a patient by Zouboulis et al. (1994) and has been reported by different authors in four additional patients since then. We have reviewed the five almost identical cases that have been reported in 20 years and we suggest the existence of a new rare syndrome characterized by the trias keratosis pilaris, ulerythema ophryogenes and monosomy 18p. Recognition of the syndrome could assist in early diagnosis of monosomy 18p in these patients.
Infantile generalized pustular psoriasis: Successful disease control with intermittent etretinate
Authors: Namba Chika , Murakami Masamoto , Hanakawa Yasushi , Tohyama Mikiko , Shirakata Yuji , Tauchi Hisamichi , Sayama Koji
Published: May 2014

Infantile generalized pustular psoriasis is a rare form of psoriasis and the best treatment is controversial. We experienced a 2‐year‐old female with erythema on her neck and axilla starting at 3 months of age. She presented with recurrent annular and geographic scaly erythema with a few pustules on the neck, precordium and axilla, but no fever. The histopathology revealed subcorneal neutrophilic infiltration and microabscesses without Kogoj's spongiform pustules. The initial diagnosis was subcorneal pustular dermatosis. However, she developed widespread geographic erythema and numerous pustules over her entire body with a fever when she got a cold. A second skin biopsy revealed monolocular pustules and Kogoj's spongiform pustules in the subcorneal layer. Etretinate was administrated after a diagnosis of pustular psoriasis was made and her condition improved gradually. The choice of treatment depends on patient age, general condition and the disease severity.
Histological studies of facial acne and atrophic acne scars treated with a bipolar fractional radiofrequency system
Authors: Kaminaka Chikako , Uede Mikiko , Nakamura Yasushi , Furukawa Fukumi , Yamamoto Yuki
Published: May 2014

Various fractional radiofrequency (FRF) treatments have demonstrated significant beneficial effects and minor side‐effects on atrophic acne scars and acne vulgaris by creating micro‐thermal injuries in the skins. However, histological studies to identify the precise mechanism responsible for the success of bipolar FRF treatments are lacking. In this study, six human subjects with these diseases were histologically analyzed after treatment with a bipolar FRF system (eMatrix; Syneron, Yokneam, Israel) and the effects of multiple passes were compared. Histopathological results showed that two‐pass FRF treatment created deeper dermal thermal injury zones compared to one‐pass treatment. Periadnexal collagen was coagulated, as well as that in the sebaceous glands, as evaluated in all cases with two‐pass FRF treatment. No severe side‐effects were observed after treatment. Our experience suggests that the level of dermal thermal injury is directly related to the number of passes, and that a large benefit of this treatment for these diseases is the preservation of adnexal structures.
Land sharing vs. land sparing: does the compact city reconcile urban development and biodiversity conservation?
Authors: Soga Masashi , Yamaura Yuichi , Koike Shinsuke , Gaston Kevin J.
Published: May 2014

As cities around the world rapidly expand, there is an urgent need to implement the best development form to minimize the negative impacts of urbanization on native biodiversity. Two divergent forms for the expansion of cities are land‐sharing and land‐sparing developments. To date, their relative benefits for biodiversity conservation are poorly understood.

We quantified the relative conservation benefits of land‐sharing and land‐sparing developments for butterflies and ground beetles inTokyo,Japan. For each insect species, we determined which approach resulted in a larger total population size.

At a higher level of urbanization (higher number of buildings in a landscape), land sparing rather than land sharing resulted in a higher total population size for the majority species of both taxa. However, at a lower level of urbanization, butterflies and ground beetles showed different responses to city development forms. Ground beetles had their highest total population sizes under land sparing, whereas for butterflies, especially open‐land and matrix‐dwelling species, larger populations were achieved under land sharing.

The negative impacts of urbanization on biodiversity differ greatly between land‐sharing and land‐sparing development forms. We also revealed that the relative conservation benefits of land sharing and land sparing depend on the level of urbanization.

Synthesis and applications. In areas that will be heavily urbanized in the future, city planners and policymakers should adopt approaches that follow a land‐sparing strategy and that keep large blocks of greenspace free from development. At lower levels of urbanization, on the other hand, as land sharing was suggested to be the better strategy for many butterfly species, a hybrid development form could be adopted that integrates areas of land sharing and land sparing, which might have the additional benefit of enhancing the delivery of some ecosystem services by bringing nature and people closer together in some areas.
Controls of vegetation structure and net primary production in restored grasslands
Authors: Munson Seth M. , Lauenroth William K.
Published: May 2014

Vegetation structure and net primary production (NPP) are fundamental properties of ecosystems. Understanding how restoration practices following disturbance interact with environmental factors to control these properties can provide insight on how ecosystems recover and guide management efforts.

We assessed the relative contribution of environmental and restoration factors in controlling vegetation structure, above‐ and below‐ground investment in production across a chronosequence of semi‐arid Conservation Reserve Program (CRP) fields recovering from dry land wheat cropping relative to undisturbed grassland. Importantly, we determined the role of plant diversity and how seeding either native or introduced perennial grasses influenced the recovery of vegetation properties.

Plant basal cover increased with field age and was highest in CRP fields seeded with native perennial grasses. In contrast, fields seeded with introduced perennial grasses had tall‐growing plants with relatively low basal cover. These vegetation structural characteristics interacted with precipitation, but not soil characteristics, to influence above‐ground NPP (ANPP). Fields enrolled in the CRP for >7 years supported twice as much ANPP as undisturbed shortgrass steppe in the first wet year of the study, but all CRP fields converged on a common low amount of ANPP in the following dry year and invested less than half as much as the shortgrass steppe in below‐ground biomass.

ANPP in CRP fields seeded with native perennial grasses for > 7 years was positively related to species richness, whereas ANPP in CRP fields seeded with introduced perennial grasses was controlled more by dominant species.

Synthesis and applications. Seeding with introduced, instead of native, perennial grasses had a strong direct influence on vegetation structure, including species richness, which indirectly affected NPP through time. However, the effects of restoring either native or introduced grasses on NPP were secondary to low water availability. Therefore, restoration strategies that maximize basal cover and below‐ground biomass, which promote water acquisition, may lead to high resilience in semi‐arid and arid regions.
Shaping the microenvironment: evidence for the influence of a host galaxin on symbiont acquisition and maintenance in the squid‐vibrio symbiosis
Authors: Heath‐Heckman Elizabeth A. C. , Gillette Amani A. , Augustin René , Gillette Miles X. , Goldman William E. , McFall‐Ngai Margaret J.
Published: May 2014

Most bacterial species make transitions between habitats, such as switching from free living to symbiotic niches. We provide evidence that a galaxin protein, EsGal1, of the squid Euprymna scolopes participates in both: (i) selection of the specific partner Vibrio fischeri from the bacterioplankton during symbiosis onset and, (ii) modulation of V. fischeri growth in symbiotic maintenance. We identified two galaxins in transcriptomic databases and showed by quantitative reverse‐transcriptase polymerase chain reaction that one (esgal1) was dominant in the light organ. Further, esgal1 expression was upregulated by symbiosis, a response that was partially achieved with exposure to symbiont cell‐envelope molecules. Confocal immunocytochemistry of juvenile animals localized EsGal1 to the apical surfaces of light‐organ epithelia and surrounding mucus, the environment in which V. fischeri cells aggregate before migration into the organ. Growth assays revealed that one repeat of EsGal1 arrested growth of Gram‐positive bacterial cells, which represent the cell type first ‘winnowed’ during initial selection of the symbiont. The EsGal1‐derived peptide also significantly decreased the growth rate of V. fischeri in culture. Further, when animals were exposed to an anti‐EsGal1 antibody, symbiont population growth was significantly increased. These data provide a window into how hosts select symbionts from a rich environment and govern their growth in symbiosis.
The Crc and Hfq proteins of Pseudomonas putida cooperate in catabolite repression and formation of ribonucleic acid complexes with specific target motifs
Authors: Moreno Renata , Hernández‐Arranz Sofía , La Rosa Ruggero , Yuste Luis , Madhushani Anjana , Shingler Victoria , Rojo Fernando
Published: May 2014

The Crc protein is a global regulator that has a key role in catabolite repression and optimization of metabolism in Pseudomonads. Crc inhibits gene expression post‐transcriptionally, preventing translation of mRNAs bearing an AAnAAnAA motif [the catabolite activity (CA) motif] close to the translation start site. Although Crc was initially believed to bind RNA by itself, this idea was recently challenged by results suggesting that a protein co‐purifying with Crc, presumably the Hfq protein, could account for the detected RNA‐binding activity. Hfq is an abundant protein that has a central role in post‐transcriptional gene regulation. Herein, we show that the Pseudomonas putida Hfq protein can recognize the CA motifs of RNAs through its distal face and that Crc facilitates formation of a more stable complex at these targets. Crc was unable to bind RNA in the absence of Hfq. However, pull‐down assays showed that Crc and Hfq can form a co‐complex with RNA containing a CA motif in vitro. Inactivation of the hfq or the crc gene impaired catabolite repression to a similar extent. We propose that Crc and Hfq cooperate in catabolite repression, probably through forming a stable co‐complex with RNAs containing CA motifs to result in inhibition of translation initiation.
Mannitol‐1‐phosphate dehydrogenases/phosphatases: a family of novel bifunctional enzymes for bacterial adaptation to osmotic stress
Authors: Sand Miriam , Rodrigues Marta , González José M. , de Crécy‐Lagard Valérie , Santos Helena , Müller Volker , Averhoff Beate
Published: May 2014

The nutritionally versatile soil bacteriumAcinetobacter baylyi ADP1 copes with salt stress by the accumulation of compatible solutes, a strategy that is widespread in nature. This bacterium synthesizes the sugar alcohol mannitolde novoin response to osmotic stress. In a previous study, we identifiedMtlD, a mannitol‐1‐phosphate dehydrogenase, which is essential for mannitol biosynthesis and which catalyses the first step in mannitol biosynthesis, the reduction of fructose‐6‐phosphate (F‐6‐P) to the intermediate mannitol‐1‐phosphate (Mtl‐1‐P). Until now, the identity of the second enzyme, the phosphatase that catalyses the dephosphorylation ofMtl‐1‐Pto mannitol, was elusive. Here we show thatMtlDhas a unique sequence among known mannitol‐1‐phosphate dehydrogenases with a haloacid dehalogenase (HAD)‐like phosphatase domain at theN‐terminus. This domain is indeed shown to have a phosphatase activity. Phosphatase activity is strictlyMg2+dependent. Nuclear magnetic resonance analysis revealed that purifiedMtlDcatalyses not only reduction ofF‐6‐Pbut also dephosphorylation ofMtl‐1‐P.MtlDofA. baylyiis the first bifunctional enzyme of mannitol biosynthesis that combinesMtl‐1‐Pdehydrogenase and phosphatase activities in a single polypeptide chain. Bioinformatic analysis revealed that the bifunctional enzyme is widespread amongAcinetobacterstrains but only rarely present in other phylogenetic tribes.
The type Tánicc in the Old Irish glosses: affix ordering, frequency and phonotactics
Authors: García‐Castillero Carlos
Published: May 2014

In this paper I investigate OIr. lexical compound verbs with the basic deuterotonic (deut.) shape CV·VC‐, of the type of expected *do·ánicc ‘he, she came’ or ‘who came’ which actually occurs in the prototonic (prot.) form tánicc. On the basis of the notions of affix ordering, frequency and junctural phonotactics developed in recent works on experimental psycholinguistics, the OIr. forms of the type tánicc are explained as relatively late innovations in which the deut. are replaced by prot. forms. The extension of the prot. form in those lexical compound verbs at the expense of the deut. form is due to the phonotactically problematic hiatus of the latter and depends mainly on grammatical (in leniting relative clause forms) and lexical (in the most frequent verbs) criteria.
Does a Nearby Murder Affect Housing Prices and Rents? The Case of Sydney
Authors: Klimova Anastasia , Lee Adrian D.
Published: May 2014

We measure the impact of murders on prices and rents of homes in Sydney. We find that housing prices fall by 3.9 per cent for homes within 0.2 miles of the murder in the year following the murder, and weaker results in the second year after a murder. We do not find any effects of murders on rents. Higher media coverage and being located closer to the murder (within 0.1 mile) have no additional effect on prices. Taken together, our findings suggest that proximity to a murder affects nearby property prices, particularly in the first year after the incident.
Rapid Differentiation of Listeria monocytogenes Epidemic Clones III and IV and Their Intact Compared with Heat‐Killed Populations Using Fourier Transform Infrared Spectroscopy and Chemometrics
Authors: Nyarko Esmond B. , Puzey Kenneth A. , Donnelly Catherine W.
Published: May 2014

The objectives of this study were to determine if Fourier transform infrared (FT‐IR) spectroscopy and multivariate statistical analysis (chemometrics) could be used to rapidly differentiate epidemic clones (ECs) of Listeria monocytogenes, as well as their intact compared with heat‐killed populations. FT‐IR spectra were collected from dried thin smears on infrared slides prepared from aliquots of 10 μL of each L. monocytogenes ECs (ECIII: J1‐101 and R2‐499; ECIV: J1‐129 and J1‐220), and also from intact and heat‐killed cell populations of each EC strain using 250 scans at a resolution of 4 cm−1 in the mid‐infrared region in a reflectance mode. Chemometric analysis of spectra involved the application of the multivariate discriminant method for canonical variate analysis (CVA) and linear discriminant analysis (LDA). CVA of the spectra in the wavelength region 4000 to 600 cm−1 separated the EC strains while LDA resulted in a 100% accurate classification of all spectra in the data set. Further, CVA separated intact and heat‐killed cells of each EC strain and there was 100% accuracy in the classification of all spectra when LDA was applied. FT‐IR spectral wavenumbers 1650 to 1390 cm−1 were used to separate heat‐killed and intact populations of L. monocytogenes. The FT‐IR spectroscopy method allowed discrimination between strains that belong to the same EC. FT‐IR is a highly discriminatory and reproducible method that can be used for the rapid subtyping of L. monocytogenes, as well as for the detection of live compared with dead populations of the organism.
SimRAD: an R package for simulation‐based prediction of the number of loci expected in RADseq and similar genotyping by sequencing approaches
Authors: Lepais Olivier , Weir Jason T.
Published: May 2014

Application of high‐throughput sequencing platforms in the field of ecology and evolutionary biology is developing quickly with the introduction of efficient methods to reduce genome complexity. Numerous approaches for genome complexity reduction have been developed using different combinations of restriction enzymes, library construction strategies and fragment size selection. As a result, the choice of which techniques to use may become cumbersome, because it is difficult to anticipate the number of loci resulting from each method. We developed SimRAD, an R package that performs in silico restriction enzyme digests and fragment size selection as implemented in most restriction site associated DNA polymorphism and genotyping by sequencing methods. In silico digestion is performed on a reference genome or on a randomly generated DNA sequence when no reference genome sequence is available. SimRAD accurately predicts the number of loci under alternative protocols when a reference genome sequence is available for the targeted species (or a close relative) but may be unreliable when no reference genome is available. SimRAD is also useful for fine‐tuning a given protocol to adjust the number of targeted loci. Here, we outline the functionality of SimRAD and provide an illustrative example of the use of the package (available on the CRAN at http://cran.r-project.org/web/packages/SimRAD).
Spatial differentiation and price discrimination in the cement industry: evidence from a structural model
Authors: Miller Nathan H. , Osborne Matthew
Published: May 2014

We estimate a structural model of the cement industry that incorporates spatial differentiation and price discrimination, focusing on the US Southwest over 1983–2003. We leverage the structure of the model to obtain consistent estimates of the underlying parameters using data on market outcomes that are substantially aggregated. Our results indicate that transportation costs around $0.46 per tonne‐mile rationalize the data. This friction enables relatively isolated plants to obtain higher prices from nearby customers. We further find that disallowing price discrimination would create $30 million in consumer surplus annually and show how the model can identify suitable divestitures in merger analysis.
Patent examination outcomes and the national treatment principle
Authors: Webster Elizabeth , Jensen Paul H. , Palangkaraya Alfons
Published: May 2014

One of the principles enshrined in all international patent treaties is that equal treatment should be provided to inventors regardless of their nationality. Little is known about whether this “national treatment” principle is upheld in practice. We analyze whether patent examination outcomes at the European and Japanese patent offices vary systematically by inventor nationality and technology area, using a matched sample of 47,947 patent applications. We find that domestic inventors have a higher likelihood of obtaining a patent grant than foreign inventors and that the positive domestic inventor effect is stronger in areas of technological specialization in the domestic economy.
Subjective evaluations with performance feedback
Authors: Zábojník Ján
Published: May 2014

Firms use subjective performance evaluations to provide employees with both incentives and feedback. This article shows that if an objective measure of performance, however imperfect, is available, subjective evaluations with incentive effects can be sustained even without repeated interaction. Although full efficiency cannot be achieved in general, it is achievable if the firm can commit to a forced distribution of evaluations and employs a continuum of workers. When the number of workers is small, a forced distribution is useful only if the objective measure is poor. The model also shows that a leniency bias in evaluations can improve incentives.
Contracting officer workload, incomplete contracting, and contractual terms
Authors: Warren Patrick L.
Published: May 2014

This article estimates the causal effect of retirement‐induced workload spikes on the selection of procurement terms. In a sample of 150,000 contracts from 85 procurement offices over 11 years, increases in workload decrease reliance on competitive acquisition procedures, decrease reliance on firm‐fixed‐price contracts, increase risk of renegotiation, and increase costs. These estimates are consistent with a model of endogenously incomplete contracting. The US federal government has experienced exceptional growth in acquisitions contracting over the past decade but limited growth in acquisitions manpower. This article provides some of the facts necessary to evaluate the consequences of these shifts.
Information technology and agency in physicians' prescribing decisions
Authors: Epstein Andrew J. , Ketcham Jonathan D.
Published: May 2014

Patients rely on physicians to act as their agents when prescribing medications, yet the efforts of pharmaceutical manufacturers and prescription drug insurers may alter this agency relationship. We evaluate how formularies, and the use of information technology (IT) that provides physicians with formulary information, influence prescribing. We combine data from a randomized experiment of physicians with secondary data to eliminate bias due to patient, physician, drug, and insurance characteristics. We find that when given formulary IT, physicians' prescribing decisions are influenced by formularies far more than by pharmaceutical firms' detailing and sampling. Without IT, however, formularies' effects are much smaller.
Evidence of nickel (Ni) efflux in Ni‐tolerant ectomycorhizal Pisolithus albus isolated from ultramafic soil
Authors: Majorel Clarisse , Hannibal Laure , Ducousso Marc , Lebrun Michel , Jourand Philippe
Published: May 2014

Nickel (Ni)‐tolerant ectomycorrhizal Pisolithus albus was isolated from extreme ultramafic soils that are naturally rich in heavy metals. This study aimed to identify the specific molecular mechanisms associated with the response of P. albus to nickel. In presence of high concentration of nickel, P. albus Ni‐tolerant isolate showed a low basal accumulation of nickel in its fungal tissues and was able to perform a metal efflux mechanism. Three genes putatively involved in metal efflux were identified from the P. albus transcriptome, and their overexpression was confirmed in the mycelium that was cultivated in vitro in the presence of nickel and in fungal tissues that were sampled in situ. Cloning these genes in yeast provided significant advantages in terms of nickel tolerance (+ 31% Ni EC50) and growth (+ 83% μ) compared with controls. Furthermore, nickel efflux was also detected in the transformed yeast cells. Protein sequence analysis indicated that the genes encoded a P‐type‐ATPase, an ABC transporter and a major facilitator superfamily permease (MFS). This study sheds light on a global mechanism of metal efflux by P. albus cells that supports nickel tolerance. These specific responses to nickel might contribute to the fungal adaptation in ultramafic soil.
Biodiversity–productivity relationship in ponds: Community and metacommunity patterns along time and environmental gradients
Authors: Piñeiro‐Guerra Juan Manuel , Fagúndez‐Pachón César , Oesterheld Martín , Arim Matías
Published: May 2014

Primary production correlates with diversity in various ways. These patterns may result from the interaction of various mechanisms related to the environmental context and the spatial and temporal scale of analysis. However, empirical evidence on diversity‐productivity patterns typically considers single temporal and spatial scales, and does not include the effect of environmental variables. In a metacommunity of macrophytes in ephemeral ponds, we analysed the diversity‐productivity relationship patterns in the field, the importance of the environmental variables of pond size and heterogeneity on such relationship, and the variation of these patterns at local (community level) and landscape scales (metacommunity level) across 52 ponds on twelve occasions, over five years (2005–2009). Combining all sampling dates, there were 377 ponds and 1954 sample‐unit observations. Vegetation biomass was used as a proxy for productivity, and biodiversity was represented by species richness, evenness, and their interaction. Environmental variables comprised pond area, depth and internal heterogeneity. Productivity and species richness were not directly related at the metacommunity level, and were positively related at the community level. Taking environmental variables into account revealed positive species richness‐productivity relationships at the metacommunity level and positive quadratic relationships at the community level. Productivity showed both positive and negative linear and nonlinear relationships with the size and heterogeneity of ponds. We found a weak relationship between productivity and evenness. The identity of variables associated with productivity changed between spatial scales and through time. The pattern of relationships between productivity and diversity depends on spatial scale and environmental context, and changes idiosyncratically through time within the same ecosystem. Thus, the diversity‐productivity relationship is not only a property of the study system, but also a consequence of environmental variations and the temporal and spatial scale of analysis.
A review of echocardiography in anaesthetic and peri‐operative practice. Part 2: training and accreditation
Authors: Sharma V. , Fletcher S. N.
Published: May 2014

Echocardiography has been widely adopted as a diagnostic and monitoring tool in cardiac anaesthesia and critical care. There is considerable interest in how echocardiography could be used to benefit patients in other areas of anaesthesia and peri‐operative practice. The first part of review examines the impact and utility of echocardiography, while this second part is concerned with the matter of training and accreditation. There are a number of existing clinical protocols for the use of transthoracic echocardiography with a focused approach. Some of these, such as Focused Intensive Care Echocardiography in the UK, have been developed into structured accreditation processes with embedded supervision. Learning opportunities are now emerging for anaesthetists who wish to acquire echocardiography skills – these encompass clinical, simulation and online resources. Whilst the roll‐out of echocardiography for more widespread use in peri‐operative management is a long‐term project, it is now an appropriate time to consider how this may be achieved.
Time delays in presentation and treatment of acute scrotal pain in a provincial hospital
Authors: Johnston James W. , Larsen Peter , El‐Haddawi Falah H. , Fancourt Michael W. , Farrant Glen J. , Gilkison William T. C. , Kyle Stephen M. , Mosquera Damien A.
Published: May 2014

Background

Acute scrotal pain is a urological emergency due to the possibility of testicular torsion and subsequent testicular loss if correction is not carried out in a timely manner.

Methods

We conducted a retrospective review of all patients who underwent surgical exploration for acute scrotal pain in a provincial hospital in New Zealand between 1 January 2001 and 31 December 2010.

Results

A total of 91 cases were identified. The median delay pre‐hospital was 9 h and in‐hospital was 2.5 h. Patients who had a non‐viable testicular torsion and patients under the age of 14 had longer pre‐hospital delays of 24 and 72 h, respectively. In‐hospital delays were similar between all pathologies except for non‐viable testicular torsions with 7 h and 45 min. Viable testicular torsions had a median in‐hospital delay of 2 h and 13 min.

Conclusion

Delay from the time of testicular pain until surgical exploration is important for the chances of testicular salvage and is made up mostly of pre‐hospital delays. Patients under the age of 14 had longer delays pre‐hospital.
Human fetoplacental and fetal liver blood flow after maternal glucose loading: a cross‐sectional observational study
Authors: Haugen Guttorm , Bollerslev Jens , Henriksen Tore
Published: May 2014

Objective

To study umbilical vein and fetal liver blood flow related to fetal anthropometric measures following maternal oral glucose loading.

Design

Experimental design in a cross‐sectional observational study.

Setting

University hospital.

Population

A total of 113 low‐risk pregnancies (30–32 weeks of gestation).

Methods

Ultrasound Doppler measurements of umbilical vein and ductus venosus blood flow (ml/min) before and 2 h after completed 75‐g oral glucose tolerance test (OGTT). Liver blood flow was defined as the umbilical vein blood flow minus ductus venosus blood flow.

Main outcome measures

Changes in umbilical vein and fetal liver blood flow following OGTT related to fetal biometric measurements.

Results

In the fasting state, fetal abdominal circumference z‐scores did not correlate with any of the flow parameters; 120 min after glucose loading, the z‐scores correlated positively with the changes in umbilical vein (r = 0.25, p = 0.010) and fetal liver blood flow (r = 0.25, p = 0.009), but not with those in ductus venosus (p = 0.84). In simultaneous multiple linear regression analyses, the effects of the changes in umbilical vein or fetal liver blood flow after OGTT on the fetal abdominal circumference z‐scores were almost equal to or greater than other parameters related to fetal size (body mass index, fasting plasma glucose, parity, and sex). Fetal heart rate increased after OGTT, but did not influence the association between the blood flow parameters and fetal abdominal circumference z‐scores.

Conclusions

Changes in umbilical vein and fetal liver blood flow after glucose loading were positively related to fetal abdominal size.
The central nervous system effects of the partial GABA‐Aα2,3‐selective receptor modulator AZD7325 in comparison with lorazepam in healthy males
Authors: Chen Xia , Jacobs Gabriël , de Kam Marieke , Jaeger Judith , Lappalainen Jaakko , Maruff Paul , Smith Mark A. , Cross Alan J. , Cohen Adam , van Gerven Joop
Published: May 2014

Aims

AZD7325 is a novel α2,3‐subtype‐selective partial GABA‐A‐receptor modulator. This study investigated the pharmacodynamics of single oral doses of AZD7325 2 mg and 10 mg on the central nervous system (CNS) compared with placebo and lorazepam 2 mg.

Methods

This double‐blind, randomized, four way crossover study enrolled 16 healthy males and administered two validated CNS test batteries to measure drug effects on cognitive, neurophysiologic and psychomotor function and subjective feelings. The pharmacological selectivity of AZD7325 was compared with lorazepam by plotting saccadic peak velocity change from baseline (ΔSPV) against body sway (ΔSway) and visual analogue scale for alertness(ΔVASalertness). This analysis has previously been used to identify α2,3‐subtype‐selectivity.

Results

In contrast with the robust impairment caused by lorazepam (all P < 0.05 vs. placebo), neither dose of AZD7325 induced statistically significant effects on any pharmacodynamic measurements. Lorazepam‐induced SPV‐reduction was linearly related to changes in other neurophysiologic biomarkers. In contrast, the slopes of the regression lines were flatter for AZD7325, particularly for the Δlog(Sway) −ΔSPV relation (estimate slope, AZD7325 10 mg vs. lorazepam, difference [95% confidence interval], P value −0.00036 vs. −0.00206, 0.001704 [0.000639, 0.002768], P = 0.0018) and the ΔVASalertness−ΔSPV relationship (0.01855 vs. 0.08216, −0.06360 [−0.1046, −0.02257], P = 0.0024). AZD7325 10 mg and lorazepam induced different response patterns on VAS ‘feeling high’ and electro‐encephalography.

Conclusion

The characteristic ΔSPV‐relative effect profiles of AZD7325 vs. lorazepam suggest anxio‐selectivity related to α2,3‐selective GABAA agonism. However, exploration of higher doses may be warranted. The paucity of effects on most CNS−PD parameters also indicates a mitigated side effect pattern, with potentially lower cognitive and neurophysiological side effect burden than non‐selective benzodiazepines.
Effects of 20 mg oral Δ9‐tetrahydrocannabinol on the olfactory function of healthy volunteers
Authors: Walter Carmen , Oertel Bruno G. , Ludyga Dagmar , Ultsch Alfred , Hummel Thomas , Lötsch Jörn
Published: May 2014

Aims

Olfactory loss impairs the patient's quality of life. In individualized therapies, olfactory drug effects gain clinical importance. Molecular evidence suggests that among drugs with potential olfactory effects is Δ9‐tetrahydrocannabinol (THC), which is approved for several indications, including neuropathic pain or analgesia in cancer patients. The present study aimed at assessing the olfactory effects of THC to be expected during analgesic treatment.

Methods

The effects of 20 mg oral THC on olfaction were assessed in a placebo‐controlled, randomized cross‐over study in healthy volunteers. Using an established olfactory test (Sniffin' Sticks), olfactory thresholds, odour discrimination and odour identification were assessed in 15 subjects at baseline and 2 h after THC administration.

Results

Δ9‐Tetrahydrocannabinol impaired the performance of subjects (n = 15) in the olfactory test. Specifically, olfactory thresholds were increased and odour discrimination performance was reduced. This resulted in a significant drop in composite threshold, discrimination, identification (TDI) olfactory score by 5.5 points (from 37.7 ± 4.2 to 32.2 ± 5.6, 95% confidence interval for differences THC vs. placebo, −7.8 to −2.0, P = 0.003), which is known to be a subjectively perceptible impairment of olfactory function.

Conclusions

Considering the resurgence of THC in medical use for several pathological conditions, the present results indicate that THC‐based analgesics may be accompanied by subjectively noticeable reductions in olfactory acuity. In particular, for patients relying on their sense of smell, this might be relevant information for personalized therapy strategies.
Evidence for Involvement of Spinal RANTES in the Antinociceptive Effects of Triptolide, a Diterpene Triepoxide, in a Rat Model of Bone Cancer Pain
Authors: Hang Li‐Hua , Li Shu‐Na , Shao Dong‐Hua , Chen Zheng , Chen Yuan‐Feng , Shu Wei‐Wei
Published: May 2014

It has been shown that triptolide has beneficial effects in the treatment of neuropathic pain, but its effects on bone cancer pain (BCP) remain unclear. In this study, we aimed to explore the potential role of spinal regulated activation of normal T cell expressed and secreted (RANTES) in the antinociceptive effects of triptolide on BCP. A BCP model was induced by injecting Walker 256 mammary gland carcinoma cells into the intramedullary space of rat tibia. Intrathecal administration of triptolide (0.5, 1, 2 μg) could dose‐dependently alleviate mechanical hyperalgesia and spontaneous pain. In addition, there were also concomitant decreases in RANTES mRNA and protein expression levels in spinal dorsal horn. These results suggest that the antinociceptive effects of triptolide are related with inhibition of spinal RANTES expression in BCP rats. The findings of this study may provide a promising drug for the treatment of BCP.
Spousal overprotection is indirectly associated with poorer dietary adherence for patients with type 2 diabetes via diabetes distress when active engagement is low
Authors: Johnson Matthew D. , Anderson Jared R. , Walker Ann , Wilcox Allison , Lewis Virginia L. , Robbins David C.
Published: May 2014

Objectives

The current study sought to explore the indirect association of spousal overprotection on patient dietary adherence through the mechanism of diabetes distress and whether the link between overprotection and diabetes distress was moderated by spouse active engagement.

Method

Participants were 117 married couples in which one member had been diagnosed with type 2 diabetes and were recruited from a patient registry at a Midwestern (USA) medical centre. Data were gathered from spouses and patients through a self‐report survey instrument. The research questions were answered with structural equation modelling using the latent moderated structural equations (LMS) approach and dyadic data analytic procedures.

Results

Overprotection was associated with reduced dietary adherence indirectly via increased diabetes distress only at low levels of active engagement. The proposed model also proved superior when compared to two plausible alternatives.

Conclusions

These findings highlight the importance of understanding the nuanced associations among the different ways spouses cope with illness to achieve better diabetes outcomes and the mechanisms responsible for linking coping and dietary adherence.

Statement of contribution

What is already known on this subject?

Spousal coping behaviour can influence dietary adherence among patients diagnosed with type 2 diabetes, positively and negatively.

Spouses simultaneously engage in different ways of coping with partner illness, but little is known about the interactive nature of coping styles or possible mechanisms that might link coping with illness outcomes.

What does this study add?

Spousal overprotection is only associated with reduced patient dietary adherence when spouses are also engaging in low levels of active engagement.

Diabetes distress is an important mechanism linking spousal coping with patient dietary adherence.
The association between stunting and psychosocial development among preschool children: a study using the South African Birth to Twenty cohort data
Authors: Casale D. , Desmond C. , Richter L.
Published: May 2014

Background

A large literature in developing countries finds a strong association between stunting in early childhood and educational attainment and/or cognitive performance among children of school‐going age. We contribute to the literature on the effects of stunting in childhood by exploring the links between linear growth retardation and measures of development among preschool‐aged children.

Methods

We analyse the association between stunting (height‐for‐age z‐score <−2) at age 2 years and children's scores on the Vineland Social Maturity Scale (VSMS) at age 4 years, a measure of social competence or ‘daily living skills’, and the Revised‐Denver Prescreening Developmental Questionnaire (R‐DPDQ) at age 5 years, a test which places greater emphasis on cognitive functioning. The sample is drawn from the Birth to Twenty cohort study, a prospective dataset of children born in 1990 in urban South Africa. We conduct multivariate regression analysis controlling for socio‐economic status, various child‐specific characteristics, home environment and caregiver inputs.

Results

No significant association between stunting and children's performance on the VSMS, but a large and significant association with the R‐DPDQ scores, was found. A disaggregated analysis of the various components of the scores suggests that children with low height‐for‐age at 2 years do not fall behind in terms of daily living skills or social maturity, but do substantially worse on measures capturing higher order fine motor skills and cognitive functioning.

Conclusions

Stunting in early childhood is strongly related to impaired cognitive functioning in children of preschool age, but does not seem to affect social maturity, at least as measured by the VSMS. These relationships between stunting at 2 years and psychosocial development at 4 and 5 years hold with extensive controls for socio‐economic status, home environment, caregiver inputs and child characteristics included in the multivariate analysis.
IL‐21 receptor signalling partially mediates Th2‐mediated allergic airway responses
Authors: Lajoie S. , Lewkowich I. , Herman N. S. , Sproles A. , Pesce J. T. , Wynn T. A. , Grusby M. J. , Hamid Q. , Wills‐Karp M.
Published: May 2014

Background

Interleukin‐21 (IL‐21) has been implicated in the development of Th2‐mediated immune responses; however, the exact role it plays in allergic diseases is not well understood.

Objective

To elucidate the contribution of IL‐21 receptor signalling to Th2‐dependent immune responses in the lung.

Methods

We compared allergic airway responses in wild‐type BALB/c and Il21r‐deficient mice exposed to local airway challenge with house dust mite (HDM).

Results

We demonstrate that IL‐21R‐deficiency reduces HDM‐driven airway hyperresponsiveness (AHR) with only partial effects on airway inflammation. Concomitant with the reduction in AHR in Il21r‐deficient mice, significant suppression was observed in protein levels of the Th2 cytokines IL‐4, and IL‐13. In contrast, IL‐21R‐deficiency was associated with an increase in PBS‐ and allergen‐driven IgE levels, while IgG1 and IgG2a levels were decreased. Moreover, our results suggest that IL‐21 may contribute to AHR through its ability to both directly induce Th2 cell survival and to impair regulatory T‐cell suppression of Th2 cytokine production. Importantly, we show that IL‐21‐positive cells are increased in the bronchial mucosa of asthmatics compared with non‐asthmatics.

Conclusion

These results suggest that IL‐21 plays an important role in the allergic diathesis by enhancing Th2 cytokine production through multiple mechanisms including the suppression of Treg inhibitory effects on Th2 cell cytokine production.