bluuebunny/crossref_metadata_2025 huggingface dataset:
Intracranial Complications of Pediatric Sinusitis
Authors: Wiersma Alexandria J. , Vu Tien
Published: June 2017

“Headache and fever” is a common presentation to the urgent care and emergency department setting and can have many etiologies. We present a case of a 10-year-old girl who presented with headache and fever and was found to have intracranial extension of sinusitis despite lack of typical sinus or chronic upper respiratory tract infection symptoms. This case illustrates the need in the emergency department or urgent care to keep a broad differential diagnosis for pediatric headache, especially when initial interventions are unsuccessful. We also review the epidemiology of pediatric sinusitis, age at sinus development, and associated intracranial complications.
Development of a Trigger Tool to Identify Adverse Drug Events in Elderly Patients With Multimorbidity
Authors: Toscano Guzmán María Dolores , Galván Banqueri Mercedes , Otero María José , Alfaro Lara Eva Rocío , Casajus Lagranja Pilar , Santos Ramos Bernardo
Published: June 2017

Purpose

Elderly patients with multimorbidity are especially vulnerable to adverse drug events (ADEs) and had high prevalence rates. Identifying ADEs is essential for enabling timely interventions that can mitigate the adverse events detected and for developing targeted strategies to prevent their occurrence as well as to monitor implementation. The aim of this study was to develop a set with appropriate triggers for detecting potential ADEs in elderly patients with multimorbidity.

Methods

A modified Delphi methodology was used to reach consensus. Existing triggers for detecting ADEs in adult patients were identified from a literature search in several databases (EMBASE, MEDLINE, Web of Science, Centre for Reviews and Dissemination, and Cochrane Library) and from Institute for Healthcare Improvement published lists. Twelve experts in patient/medication safety or in chronic diseases scored candidate triggers for appropriateness according to 3 criteria (evidence, usefulness for elderly patients, and feasibility of implementation in clinical practice).

Results

Seventy-two triggers were initially selected to be evaluated. The final set includes a total of 51 triggers for which the panelists who completed the 2 rounds of evaluation reached agreement. These triggers were organized into 5 modules: 11 as care module triggers, 10 as antidotes/treatment, 11 medication concentrations, 18 abnormal laboratory values, and 1 as emergency department trigger.

Conclusions

A set of triggers for detecting ADEs in elderly patients with multimorbidity have been developed, following the consensus of a panel of experts. Subsequent validation in clinical practice is needed to confirm the accuracy and efficiency of these triggers for this population.
A Comparison of Clinical Characteristics and Outcomes of Ventilator-Associated Pneumonias Among Burn Patients by Diagnostic Criteria Set
Authors: Younan Duraid , Griffin Russell , Swain Thomas , Schinnerer Eric , Pittet Jean-Francois , Camins Bernard
Published: June 2017

Objectives:

The National Healthcare Safety Network (NHSN) replaced its old definition for ventilator-associated pneumonia (VAP) with ventilator-associated events (VAEs) in 2013. Little data is available comparing the two definitions in burn patients.

Methods:

Data from 2011 to 2014 were collected on burn patients mechanically ventilated for at least 2 days. VAP was determined using two methods: (1) pneumonia as defined by the previous more clinical CDC (NHSN) definition captured in the burn registry; (2) pneumonia as defined by the recent CDC (NHSN) standard of VAEs where patients meeting the criteria for possible VAP were considered having a pneumonia. Cohen kappa statistic was measured to compare both definitions, and chi-square and ANOVA to compare admission and clinical outcomes.

Results:

There were 266 burn patients who were mechanically ventilated for at least 2 days between 2011 and 2014. One hundred patients (37.5%) met the criteria by the old definition and 35 (13.1%) met the criteria for both. The kappa statistic was 0.34 (95% confidence interval 0.23–0.45), suggesting weak agreement. Those who met both definitions were mechanically ventilated for a longer period of time (P = 0.0003), and had a longer intensive care unit (ICU) length of stay (LOS) (P = 0.0004) and hospital LOS (P = 0.0014).

Conclusions:

There is weak agreement between the two definitions of VAP in severely burn patients. However, patients who met both VAP definitions had longer ventilator days, ICU, and hospital stays.
A circannual perspective on daily and total flight distances in a long-distance migratory raptor, the Montagu's harrier,
Circus pygargus
Authors: Schlaich Almut E. , Bouten Willem , Bretagnolle Vincent , Heldbjerg Henning , Klaassen Raymond H. G. , Sørensen Iben H. , Villers Alexandre , Both Christiaan
Published: June 2017

Long-distance migrants are particularly recognized for the distances covered on migration, yet little is known about the distances they cover during the rest of the year. GPS-tracks of 29 Montagu's harriers from breeding areas in France, The Netherlands and Denmark showed that harriers fly between 35 653 and 88 049 km yr
−1
, of which on average only 28.5% is on migration. Mean daily distances during migration were 296 km d
−1
in autumn and 252 km d
−1
in spring. Surprisingly, males' daily distances during breeding (217 km d
−1
) were close to those during migration, whereas breeding females moved significantly less (101 km d
−1
) than males. In terms of flight distance, the breeding season seemed nearly as demanding as migration periods for males. During the six winter months, both sexes moved less (114 and 128 km d
−1
for females and males, respectively) than during migration. Harriers therefore covered shorter daily distances during winter which might allow birds to compensate for the more demanding phases of migration and breeding.
Body shape convergence driven by small size optimum in marine angelfishes
Authors: Frédérich Bruno , Santini Francesco , Konow Nicolai , Schnitzler Joseph , Lecchini David , Alfaro Michael E.
Published: June 2017

Convergent evolution of small body size occurs across many vertebrate clades and may reflect an evolutionary response to shared selective pressures. However it remains unclear if other aspects of phenotype undergo convergent evolution in miniaturized lineages. Here we present a comparative analysis of body size and shape evolution in marine angelfishes (Pomacanthidae), a reef fish family characterized by repeated transitions to small body size. We ask if lineages that evolve small sizes show convergent evolution in body shape. Our results reveal that angelfish lineages evolved three different stable size optima with one corresponding to the group of pygmy angelfishes (
Centropyge
). Then, we test if the observed shifts in body size are associated with changes to new adaptive peaks in shape. Our data suggest that independent evolution to small size optima have induced repeated convergence upon deeper body and steeper head profile in
Centropyge
. These traits may favour manoeuvrability and visual awareness in these cryptic species living among corals, illustrating that functional demands on small size may be related to habitat specialization and predator avoidance. The absence of shape convergence in large marine angelfishes also suggests that more severe requirements exist for small than for large size optima.
Enhanced osteointegration of poly(methylmethacrylate) bone cements by incorporating strontium-containing borate bioactive glass
Authors: Cui Xu , Huang Chengcheng , Zhang Meng , Ruan Changshun , Peng Songlin , Li Li , Liu Wenlong , Wang Ting , Li Bing , Huang Wenhai , Rahaman Mohamed N. , Lu William W. , Pan Haobo
Published: June 2017

Although poly(methylmethacrylate) (PMMA) cements are widely used in orthopaedics, they have numerous drawbacks. This study aimed to improve their bioactivity and osseointegration by incorporating strontium-containing borate bioactive glass (SrBG) as the reinforcement phase and bioactive filler of PMMA cement. The prepared SrBG/PMMA composite cements showed significantly decreased polymerization temperature when compared with PMMA and retained properties of appropriate setting time and high mechanical strength. The bioactivity of SrBG/PMMA composite cements was confirmed
in vitro
, evidenced by ion release (Ca, P, B and Sr) from SrBG particles. The cellular responses of MC3T3-E1 cells
in vitro
demonstrated that SrBG incorporation could promote adhesion, migration, proliferation and collagen secretion of cells. Furthermore, our
in vivo
investigation revealed that SrBG/PMMA composite cements presented better osseointegration than PMMA bone cement. SrBG in the composite cement could stimulate new-bone formation around the interface between the composite cement and host bone at eight and 12 weeks post-implantation, whereas PMMA bone cement only stimulated development of an intervening connective tissue layer. Consequently, the SrBG/PMMA composite cement may be a better alternative to PMMA cement in clinical applications and has promising orthopaedic applications by minimal invasive surgery.
Macromolecular crowding directs the motion of small molecules inside cells
Authors: Smith Stephen , Cianci Claudia , Grima Ramon
Published: June 2017

It is now well established that cell interiors are significantly crowded by macromolecules, which impede diffusion and enhance binding rates. However, it is not fully appreciated that levels of crowding are heterogeneous, and can vary substantially between subcellular regions. In this article, starting from a microscopic model, we derive coupled nonlinear partial differential equations for the concentrations of two populations of large and small spherical particles with steric volume exclusion. By performing an expansion in the ratio of the particle sizes, we find that the diffusion of a small particle in the presence of large particles obeys an advection–diffusion equation, with a reduced diffusion coefficient and a velocity directed towards less crowded regions. The interplay between advection and diffusion leads to behaviour that differs significantly from Brownian diffusion. We show that biologically plausible distributions of macromolecules can lead to highly non-Gaussian probability densities for the small particle position, including asymmetrical and multimodal densities. We confirm all our results using hard-sphere Brownian dynamics simulations.
Neuronal circadian clock protein oscillations are similar in behaviourally rhythmic forager honeybees and in arrhythmic nurses
Authors: Fuchikawa T. , Beer K. , Linke-Winnebeck C. , Ben-David R. , Kotowoy A. , Tsang V. W. K. , Warman G. R. , Winnebeck E. C. , Helfrich-Förster C. , Bloch G.
Published: June 2017

Internal clocks driving rhythms of about a day (circadian) are ubiquitous in animals, allowing them to anticipate environmental changes. Genetic or environmental disturbances to circadian clocks or the rhythms they produce are commonly associated with illness, compromised performance or reduced survival. Nevertheless, some animals including Arctic mammals, open sea fish and social insects such as honeybees are active around-the-clock with no apparent ill effects. The mechanisms allowing this remarkable natural plasticity are unknown. We generated and validated a new and specific antibody against the clock protein PERIOD of the honeybeeApis mellifera(amPER) and used it to characterize the circadian network in the honeybee brain. We found many similarities toDrosophila melanogasterand other insects, suggesting common anatomical organization principles in the insect clock that have not been appreciated before. Time course analyses revealed strong daily oscillations in amPER levels in foragers, which show circadian rhythms, and also in nurses that do not, although the latter have attenuated oscillations in brain mRNA clock gene levels. The oscillations in nurses show that activity can be uncoupled from the circadian network and support the hypothesis that a ticking circadian clock is essential even in around-the-clock active animals in a constant physical environment.
Excavation and aggregation as organizing factors in de novo construction by mound-building termites
Authors: Green Ben , Bardunias Paul , Turner J. Scott , Nagpal Radhika , Werfel Justin
Published: June 2017

Termites construct complex mounds that are orders of magnitude larger than any individual and fulfil a variety of functional roles. Yet the processes through which these mounds are built, and by which the insects organize their efforts, remain poorly understood. The traditional understanding focuses on stigmergy, a form of indirect communication in which actions that change the environment provide cues that influence future work. Termite construction has long been thought to be organized via a putative ‘cement pheromone’: a chemical added to deposited soil that stimulates further deposition in the same area, thus creating a positive feedback loop whereby coherent structures are built up. To investigate the detailed mechanisms and behaviours through which termites self-organize the early stages of mound construction, we tracked the motion and behaviour of major workers from two
Macrotermes
species in experimental arenas. Rather than a construction process focused on accumulation of depositions, as models based on cement pheromone would suggest, our results indicated that the primary organizing mechanisms were based on excavation. Digging activity was focused on a small number of excavation sites, which in turn provided templates for soil deposition. This behaviour was mediated by a mechanism of aggregation, with termites being more likely to join in the work at an excavation site as the number of termites presently working at that site increased. Statistical analyses showed that this aggregation mechanism was a response to active digging, distinct from and unrelated to putative chemical cues that stimulate deposition. Agent-based simulations quantitatively supported the interpretation that the early stage of de novo construction is primarily organized by excavation and aggregation activity rather than by stigmergic deposition.
The scaling of population persistence with carrying capacity does not asymptote in populations of a fish experiencing extreme climate variability
Authors: White Richard S. A. , Wintle Brendan A. , McHugh Peter A. , Booker Douglas J. , McIntosh Angus R.
Published: June 2017

Despite growing concerns regarding increasing frequency of extreme climate events and declining population sizes, the influence of environmental stochasticity on the relationship between population carrying capacity and time-to-extinction has received little empirical attention. While time-to-extinction increases exponentially with carrying capacity in constant environments, theoretical models suggest increasing environmental stochasticity causes asymptotic scaling, thus making minimum viable carrying capacity vastly uncertain in variable environments. Using empirical estimates of environmental stochasticity in fish metapopulations, we showed that increasing environmental stochasticity resulting from extreme droughts was insufficient to create asymptotic scaling of time-to-extinction with carrying capacity in local populations as predicted by theory. Local time-to-extinction increased with carrying capacity due to declining sensitivity to demographic stochasticity, and the slope of this relationship declined significantly as environmental stochasticity increased. However, recent 1 in 25 yr extreme droughts were insufficient to extirpate populations with large carrying capacity. Consequently, large populations may be more resilient to environmental stochasticity than previously thought. The lack of carrying capacity-related asymptotes in persistence under extreme climate variability reveals how small populations affected by habitat loss or overharvesting, may be disproportionately threatened by increases in extreme climate events with global warming.
eIF4A is stimulated by the pre-initiation complex and enhances recruitment of mRNAs regardless of structural complexity
Authors: Yourik Paul , Aitken Colin Echeverría , Zhou Fujun , Gupta Neha , Hinnebusch Alan G. , Lorsch Jon R.
Published: June 2017

eIF4A is a DEAD-box RNA-dependent ATPase thought to unwind RNA secondary structure in the 5′-untranslated regions (UTRs) of mRNAs to promote their recruitment to the eukaryotic translation pre-initiation complex (PIC). We show that eIF4A’s ATPase activity is markedly stimulated in the presence of the PIC, independently of eIF4E•eIF4G, but dependent on subunits i and g of the heteromeric eIF3 complex. Surprisingly, eIF4A accelerated the rate of recruitment of all mRNAs tested, regardless of their degree of structural complexity. Structures in the 5′-UTR and 3′ of the start codon synergistically inhibit mRNA recruitment in a manner relieved by eIF4A, indicating that the factor does not act solely to melt hairpins in 5′-UTRs. Our findings that eIF4A functionally interacts with the PIC and plays important roles beyond unwinding 5’-UTR structure is consistent with a recent proposal that eIF4A modulates the conformation of the 40S ribosomal subunit to promote mRNA recruitment.
An open resource for transdiagnostic research in pediatric mental health and learning disorders
Authors: Alexander Lindsay M. , Escalera Jasmine , Ai Lei , Andreotti Charissa , Febre Karina , Mangone Alexander , Potler Natan Vega , Langer Nicolas , Alexander Alexis , Kovacs Meagan , Litke Shannon , O’Hagan Bridget , Andersen Jennifer , Bronstein Batya , Bui Anastasia , Bushey Marijayne , Butler Henry , Castagna Victoria , Camacho Nicolas , Chan Elisha , Citera Danielle , Clucas Jon , Cohen Samantha , Dufek Sarah , Eaves Megan , Fradera Brian , Gardner Judith , Grant-Villegas Natalie , Green Gabriella , Gregory Camille , Hart Emily , Harris Shana , Horton Megan , Kahn Danielle , Kabotyanski Katherine , Karmel Bernard , Kelly Simon P. , Kleinman Kayla , Koo Bonhwang , Kramer Eliza , Lennon Elizabeth , Lord Catherine , Mantello Ginny , Margolis Amy , Merikangas Kathleen R. , Milham Judith , Minniti Giuseppe , Neuhaus Rebecca , Nussbaum Alexandra , Osman Yael , Parra Lucas C. , Pugh Ken R. , Racanello Amy , Restrepo Anita , Saltzman Tian , Septimus Batya , Tobe Russell , Waltz Rachel , Williams Anna , Yeo Anna , Castellanos Francisco X. , Klein Arno , Paus Tomas , Leventhal Bennett L. , Craddock R. Cameron , Koplewicz Harold S. , Milham Michael P.
Published: June 2017

Technological and methodological innovations are equipping researchers with unprecedented capabilities for detecting and characterizing pathologic processes in the developing human brain. As a result, ambitions to achieve clinically useful tools to assist in the diagnosis and management of mental health and learning disorders are gaining momentum. To this end, it is critical to accrue large-scale multimodal datasets that capture a broad range of commonly encountered clinical psychopathology. The Child Mind Institute has launched the Healthy Brain Network (HBN), an ongoing initiative focused on creating and sharing a biobank of data from 10,000 New York area participants (ages 5-21). The HBN Biobank houses data about psychiatric, behavioral, cognitive, and lifestyle phenotypes, as well as multimodal brain imaging (resting and naturalistic viewing fMRI, diffusion MRI, morphometric MRI), electroencephalography, eye-tracking, voice and video recordings, genetics, and actigraphy. Here, we present the rationale, design and implementation of HBN protocols. We describe the first data release (n = 664) and the potential of the biobank to advance related areas (e.g., biophysical modeling, voice analysis).
Unusual Sulfur Requirements During Laboratory Growth ofLuteibacter
Authors: Baltrus David A. , Arnold A. Elizabeth
Published: June 2017

Many terrestrial bacteria are assumed to utilize sulfate transport and metabolism as a means for fulfilling cellular sulfur requirements. As such, many defined minimal media for bacterial growth under laboratory conditions contain sulfate as their sulfur source. Herein, an exception to this assumption is described as sulfate transport capabilities have been lost at least once in a lineage ofLuteibacterassociated with plants and fungi. However, a representative of this lineage (an endohyphal species,Luteibactersp. 9143) can grow in minimal media when sulfur is supplemented with organic (cysteine and methionine) or inorganic (thiosulfate) compounds, and when co-cultured with its fungal host. A related strain ofLuteibacter(UNC366Tsa5.1, isolated from the rhizosphere of Arabidopsis) potentially possesses more limited sulfur acquisition pathways thanLuteibactersp. 9143. These results highlight the surprising sulfur requirements ofLuteibacter, which may be illustrative of close associations between these strains and eukaryotes, as well as a need for caution when inferring auxotrophies in a focal strain based on differential growth in minimal versus rich media.

Importance

Sulfate is often used as the sulfur source in minimal media. Here we show that someLuteibacterstrains cannot utilize sulfate as a sulfur source, likely due to loss of genes encoding transport proteins. As sulfur requirements forLuteibactercan be met through co-culture with their fungal partner, this knowledge could provide a means to engineer better symbiotic relationships between bacteria and fungi that may be relevant for agriculture. Because growth in minimal media can be restored by supplementation with either cysteine or methionine, and in some cases only methionine, this result highlights how unexpected growth requirements could masquerade as auxotrophy for certain strains and conditions.
Direct and Inverted Repeat stimulated excision (DIRex): Simple, single-step, and scar-free mutagenesis of bacterial genes
Authors: Näsvall Joakim
Published: June 2017

The need for generating precisely designed mutations is common in genetics, biochemistry, and molecular biology. Here, I describe a new λ Red recombineering method (Direct andInvertedRepeat stimulatedexcision; DIRex) for fast and easy generation of single point mutations, small insertions or replacements as well as deletions of any size, in bacterial genes. The method does not leave any resistance marker or scar sequence and requires only one transformation to generate a semi-stable intermediate insertion mutant. Spontaneous excision of the intermediate efficiently and accurately generates the final mutant. In addition, the intermediate is transferable between strains by generalized transductions, enabling transfer of the mutation into multiple strains without repeating the recombineering step. Existing methods that can be used to accomplish similar results are either (i) more complicated to design, (ii) more limited in what mutation types can be made, or (iii) require expression of extrinsic factors in addition to λ Red. I demonstrate the utility of the method by generating several deletions, small insertions/replacements, and single nucleotide exchanges inEscherichia coliandSalmonella enterica. Furthermore, the design parameters that influence the excision frequency and the success rate of generating desired point mutations have been examined to determine design guidelines for optimal efficiency.
Non-Parametric Genetic Prediction of Complex Traits with Latent Dirichlet Process Regression Models
Authors: Zeng Ping , Zhou Xiang
Published: June 2017

Using genotype data to perform accurate genetic prediction of complex traits can facilitate genomic selection in animal and plant breeding programs, and can aid in the development of personalized medicine in humans. Because most complex traits have a polygenic architecture, accurate genetic prediction often requires modeling all genetic variants together via polygenic methods. Here, we develop such a polygenic method, which we refer to as the latent Dirichlet process regression model (DPR). DPR is non-parametric in nature, relies on the Dirichlet process to flexibly and adaptively model the effect size distribution, and thus enjoys robust prediction performance across a broad spectrum of genetic architectures. We compare DPR with several commonly used prediction methods with simulations. We further apply DPR to predict gene expressions, to conduct PrediXcan based gene set test, to perform genomic selection of four traits in two species, and to predict eight complex traits in a human cohort.
Repeated imitation makes human vocalizations more word-like
Authors: Edmiston Pierce , Perlman Marcus , Lupyan Gary
Published: June 2017

People have long pondered the evolution of language and the origin of words. Here, we investigate how conventional spoken words might emerge from imitations of environmental sounds. Does the repeated imitation of an environmental sound gradually give rise to more word-like forms? In what ways do these forms resemble the original sounds that motivated them (i.e., exhibit iconicity)? Participants played a version of the children’s game “Telephone”. The first generation of participants imitated recognizable environmental sounds (e.g., glass breaking, water splashing). Subsequent generations imitated the previous generation of imitations for a maximum of 8 generations. The results showed that the imitations became more stable and word-like, and later imitations were easier to learn as category labels. At the same time, even after 8 generations, both spoken imitations and their written transcriptions could be matched above chance to the category of environmental sound that motivated them. These results show how repeated imitation can create progressively more word-like forms while continuing to retain a resemblance to the original sound that motivated them, and speak to the possible role of human vocal imitation in explaining the origins of at least some spoken words.
The likelihood of heterogeneity or additional mutation in KRAS or associated oncogenes to compromise targeting of oncogenic KRAS G12C
Authors: Cannataro Vincent L. , Gaffney Stephen G. , Stender Carly , Zhao Zi-Ming , Philips Mark , Greenstein Andrew E. , Townsend Jeffrey P.
Published: June 2017

Activating mutations in RAS genes are associated with approximately 20% of all human cancers. New targeted therapies show preclinical promise in inhibiting the KRAS G12C variant, however, concerns exist regarding the effectiveness of such therapiesin vivogiven the possibilities of existing intratumor heterogeneity orde novomutation leading to treatment resistance. We performed deep sequencing of 27 KRAS G12 positive lung tumors and found no evidence of other oncogenic mutations within KRAS or within commonly mutated downstream genes that could confer resistance at the time of treatment. Furthermore, we estimate thede novomutation rate in KRAS position 12 and in genes downstream ofKRAS.We find that mutations that confer resistance are about as likely to occur downstream of KRAS as within KRAS. Moreover, we present an approach for estimation of the selection intensity for these point mutations that explains their high prevalence in tumors. Our approach predicts that BRAF V600E would provide the highest fitness advantage forde novoresistant subclones. Overall, our findings suggest that resistance to targeted therapy of KRAS G12C positive tumors is unlikely to be present at the time of treatment and, among thede novomutations likely to confer resistance, mutations in BRAF, a gene with targeted inhibitors presently available, result in subclones with the highest fitness advantage.

One Sentence Summary

Mutations conferring resistance to KRAS G12C targeted therapy are unlikely to be present at the time of resection, and the likely mechanisms of evolved resistance are predicted be ones that are responsive to therapies that are in development or that are already available.
Drivers of genetic diversity in secondary metabolic gene clusters within a fungal species
Authors: Lind Abigail L. , Wisecaver Jennifer H. , Lameiras Catarina , Wiemann Philipp , Palmer Jonathan M. , Keller Nancy P. , Rodrigues Fernando , Goldman Gustavo H. , Rokas Antonis
Published: June 2017

Filamentous fungi produce a diverse array of secondary metabolites (SMs) critical for defense, virulence, and communication. The metabolic pathways that produce SMs are found in contiguous gene clusters in fungal genomes, an atypical arrangement for metabolic pathways in other eukaryotes. Comparative studies of filamentous fungal species have shown that SM gene clusters are often either highly divergent or uniquely present in one or a handful of species, hampering efforts to determine the genetic basis and evolutionary drivers of SM gene cluster divergence. Here we examined SM variation in 66 cosmopolitan strains of a single species, the opportunistic human pathogenAspergillus fumigatus. Investigation of genome-wide within-species variation revealed five general types of variation in SM gene clusters: non-functional gene polymorphisms, gene gain and loss polymorphisms, whole cluster gain and loss polymorphisms, allelic polymorphisms where different alleles corresponded to distinct, non-homologous clusters, and location polymorphisms in which a cluster was found to differ in its genomic location across strains. These polymorphisms affect the function of representativeA. fumigatusSM gene clusters, such as those involved in the production of gliotoxin, fumigaclavine, and helvolic acid, as well as the function of clusters with undefined products. In addition to enabling the identification of polymorphisms whose detection requires extensive genome-wide synteny conservation (e.g., mobile gene clusters and non-homologous cluster alleles), our approach also implicated multiple underlying genetic drivers, including point mutations, recombination, genomic deletion and insertion events, as well as horizontal gene transfer from distant fungi. Finally, most of the variants that we uncover withinA. fumigatushave been previously hypothesized to contribute to SM gene cluster diversity across entire fungal classes and phyla. We suggest that the drivers of genetic diversity operating within a fungal species shown here are sufficient to explain SM cluster macroevolutionary patterns.
CBL family E3 ubiquitin ligases control JAK2 ubiquitination and stability in hematopoietic stem cells and myeloid malignancies
Authors: Lv Kaosheng , Jiang Jing , Donaghy Ryan , Riling Christopher R. , Cheng Ying , Chandra Vemika , Rozenova Krasimira , An Wei , Mohapatra Bhopal C. , Goetz Benjamin T. , Pillai Vinodh , Han Xu , Todd Emily A. , Jeschke Grace R. , Langdon Wallace Y. , Kumar Suresh , Hexner Elizabeth O. , Band Hamid , Tong Wei
Published: June 2017

Janus kinase 2 (JAK2) is a central kinase in hematopoietic stem/progenitor cells (HSPCs), and its uncontrolled activation is a prominent oncogenic driver of hematopoietic neoplasms. However, molecular mechanisms underlying the regulation of JAK2 have remained elusive. Here we report that the Casitas B-cell lymphoma (CBL) family E3 ubiquitin ligases down-regulate JAK2 stability and signaling via the adaptor protein LNK/SH2B3. We demonstrated that depletion of CBL/CBL-B or LNK abrogated JAK2 ubiquitination, extended JAK2 half-life, and enhanced JAK2 signaling and cell growth in human cell lines as well as primary murine HSPCs. Built on these findings, we showed that JAK inhibitor (JAKi) significantly reduced aberrant HSPCs and mitigated leukemia development in a mouse model of aggressive myeloid leukemia driven by loss of Cbl and Cbl-b. Importantly, primary human CBL mutated (CBLmut) leukemias exhibited increased JAK2 protein levels and signaling and were hypersensitive to JAKi. Loss-of-function mutations in CBL E3 ubiquitin ligases are found in a wide range of myeloid malignancies, which are diseases without effective treatment options. Hence, our studies reveal a novel signaling axis that regulates JAK2 in normal and malignant HSPCs and suggest new therapeutic strategies for treating CBLmut myeloid malignancies.
Population genomics and the evolution of virulence in the fungal pathogenCryptococcus neoformans
Authors: Desjardins Christopher A. , Giamberardino Charles , Sykes Sean M. , Yu Chen-Hsin , Tenor Jennifer L. , Chen Yuan , Yang Timothy , Jones Alexander M. , Sun Sheng , Haverkamp Miriam R. , Heitman Joseph , Litvintseva Anastasia P. , Perfect John R. , Cuomo Christina A.
Published: June 2017

Cryptococcus neoformansis an opportunistic fungal pathogen that causes approximately 625,000 deaths per year from nervous system infections. Here, we leveraged a unique, genetically diverse population ofC. neoformansfrom sub-Saharan Africa, commonly isolated from mopane trees, to determine how selective pressures in the environment coincidentally adaptedC. neoformansfor human virulence. Genome sequencing and phylogenetic analysis of 387 isolates, representing the global VNI and African VNB lineages, highlighted a deep, nonrecombining split in VNB (herein, VNBI and VNBII). VNBII was enriched for clinical samples relative to VNBI, while phenotypic profiling of 183 isolates demonstrated that VNBI isolates were significantly more resistant to oxidative stress and more heavily melanized than VNBII isolates. Lack of melanization in both lineages was associated with loss-of-function mutations in theBZP4transcription factor. A genome-wide association study across all VNB isolates revealed sequence differences between clinical and environmental isolates in virulence factors and stress response genes. Inositol transporters and catabolism genes, which process sugars present in plants and the human nervous system, were identified as targets of selection in all three lineages. Further phylogenetic and population genomic analyses revealed extensive loss of genetic diversity in VNBI, suggestive of a history of population bottlenecks, along with unique evolutionary trajectories for mating type loci. These data highlight the complex evolutionary interplay between adaptation to natural environments and opportunistic infections, and that selection on specific pathways may predispose isolates to human virulence.
Theoretical and experimental study of the gradient properties and the resulting local crystalline structure and orientation in magnetron-sputtered CrAlN coatings with lateral composition and thickness gradient
Authors: Krause Bärbel , Stüber Michael , Zimina Anna , Steininger Ralph , Trappen Mareike , Ulrich Sven , Mostafavi Kashani Seyed Mohammad , Baumbach Tilo
Published: June 2017

Cr–Al–N coatings with a lateral composition gradient were deposited from two segmented Cr/Al targets with different segment size, thus covering the Al content range 0.22 ≲ c ≲ 0.87 and a thickness range from several hundred nanometres to several micrometres. The two-dimensional thickness and composition profiles were determined nondestructively from X-ray fluorescence maps. The results were reproduced by simulations of the flux distribution on the sample surface, combiningTRIDYNsimulations of the reactive sputter process at the target surface andSIMTRAsimulations of the subsequent transport through the gas phase. The phase formation was studied by spatially resolved X-ray diffraction and X-ray absorption spectroscopy at the Cr Kedge. Forc ≲ 0.69, a single-phase solid solution face-centered cubic (f.c.c.) (Cr,Al)N phase was found, and for 0.69 ≲ c ≲ 0.87 coexisting f.c.c. (Cr,Al)N and hexagonal close packed (h.c.p.) (Cr,Al)N phases were observed. The biaxial texture formation in nearly the entire composition range indicates a zone T growth. Four, mainly composition-dependent, texture regions were identified. All observed textures are closely related to textures reported for the h.c.p. AlN and f.c.c. CrN parent phases. Forc ≳ 0.69, a strong thickness dependence of the textures was observed. The measurements reveal an orientation relation between different f.c.c. and h.c.p. textures, indicating that local epitaxy might play a role in the structure formation.
3D-printed jars for ball-milling experiments monitoredin situby X-ray powder diffraction
Authors: Tumanov Nikolay , Ban Voraksmy , Poulain Agnieszka , Filinchuk Yaroslav
Published: June 2017

Mechanochemistry is flourishing in materials science, but a characterization of the related processes is difficult to achieve. Recently, the use of plastic jars in shaker mills has enabledin situX-ray powder diffraction studies at high-energy beamlines. This paper describes an easy way to design and manufacture these jars by three-dimensional (3D) printing. A modified wall thickness and the use of a thin-walled sampling groove and a two-chamber design, where the milling and diffraction take place in two communicating volumes, allow for a reduced background/absorption and higher angular resolution, with the prospect for use at lower-energy beamlines. 3D-printed polylactic acid jars show good mechanical strength and they are also more resistant to solvents than jars made of polymethyl methacrylate. The source files for printing the jars are available as supporting information.
Three-dimensional reconstruction for coherent diffraction patterns obtained by XFEL
Authors: Nakano Miki , Miyashita Osamu , Jonic Slavica , Song Changyong , Nam Daewoong , Joti Yasumasa , Tama Florence
Published: June 2017

The three-dimensional (3D) structural analysis of single particles using an X-ray free-electron laser (XFEL) is a new structural biology technique that enables observations of molecules that are difficult to crystallize, such as flexible biomolecular complexes and living tissue in the state close to physiological conditions. In order to restore the 3D structure from the diffraction patterns obtained by the XFEL, computational algorithms are necessary as the orientation of the incident beam with respect to the sample needs to be estimated. A program package for XFEL single-particle analysis based on the Xmipp software package, that is commonly used for image processing in 3D cryo-electron microscopy, has been developed. The reconstruction program has been tested using diffraction patterns of an aerosol nanoparticle obtained by tomographic coherent X-ray diffraction microscopy.
Managing the perception of service quality; the importance of understanding differences between demographic and behavioural customer segments amongst theme park visitors
Authors: Fotiadis Anestis , Kozak Metin
Published: June 2017

Purpose

The aim of this study was to investigate the differences in the perception of service quality among various demographic and behavioural visitor segments within the theme park tourism market.

Design/methodology/approach

A quantitative survey was conducted using a structured questionnaire which was distributed to 655 theme park visitors. Different groups of visitors were identified through the use of cluster analysis based on the evaluation of both demographic variables and a number of behavioural factors associated with their characteristics in terms of “time and cost” allocations for visits to a theme park.

Findings

The findings confirm that differences in demographic characteristics significantly affect perceptions of visitors as demonstrated in the way they are likely to evaluate importance and performance factors in a theme park’s delivery of services. In contrast, behavioural segmentation in terms of time allocation and associated expenditure is unlikely to produce significant differences in the visitors’ perceptions of the level of service provided.

Originality/value

Although there are many studies related to visitors’ perceived service quality, none of them use the same methodology as applied in this study of theme park industry. The research results reveal important implications for the theme park industry because of this new understanding of the segmentation differences for visitor-perceived service quality. By directing attention of management to these differences, improvements in service quality perceptions can more readily be achieved.
Indoor living plants’ effects on an office environment
Authors: Smith Andrew J. , Fsadni Andrew , Holt Gary
Published: June 2017

Purpose

The use of indoor living plants for enhancement of indoor relative humidity and the general environment of a large, modern, open plan office building are studied using a mixed-methods paradigm.

Design/methodology/approach

The quantitative element involved designated experimental and control zones within the building, selected using orientation, user density and users’ work roles criteria. For a period of six months, relative humidity was monitored using data loggers at 30 min intervals, and volatile organic compounds were measured using air sampling. Qualitative “perception data” of the building’s users were collected via a structured questionnaire survey among both experimental and control zones.

Findings

Study findings include that living plants did not achieve the positive effect on relative humidity predicted by (a-priori) theoretical calculations and that building users’ perceived improvements to indoor relative humidity, temperature and background noise levels were minimal. The strongest perceived improvement was for work environment aesthetics. Findings demonstrate the potential of indoor plants to reduce carbon emissions of the [as] built environment through elimination or reduction of energy use and capital-intensive humidification air-conditioning systems.

Originality/value

The study’s practical value lies in its unique application of (mainly laboratory-derived) existing theory in a real-life work environment.
Integrating contractor and property developer for product system innovations
Authors: Holmén Magnus , Bröchner Jan , Mokhlesian Shahin
Published: June 2017

Purpose

The aim of this paper is to explain why construction groups facing opportunities for product system innovations, such as green buildings, may choose to integrate construction and property development, taking on facilities management (FM) for a limited period.

Design/methodology/approach

Conceptual analysis based on prior literature and illustrated by a single case of integration.

Findings

For product system innovations, an in-house developer should be more able to reduce uncertainty than independent developers, due to unobservable long-term technological quality for customers, because the property becomes associated with lower risk after having been owned and operated. Alternatives such as building certification systems support incremental innovations, warranties suffer from double moral hazard in the long run and risk allocation in public–private partnership projects often fails to encourage system innovations. Integration allows the contractor to work continuously with innovative projects, developing new capabilities, which allow the firm to signal proficiency to the market, employees and the investment community.

Research limitations/implications

The phenomenon is new, and further empirical surveys are needed to confirm the hypothetical conclusions drawn here.

Practical implications

The value of close collaboration between those who develop innovative green building technologies and facilities managers is outlined.

Originality/value

The relation between the scope of corporate activities in construction groups, technological innovations and FM has not been studied before.
Operational problems and solutions of statutory complex adjudication: stakeholders’ perspectives
Authors: Skaik Samer
Published: June 2017

Purpose

Statutory adjudication was introduced into the security of payment (SOP) legislation as a fast-track payment dispute resolution process with an express object to facilitate cash flow within the construction contractual chain. After more than a decade of the operation of the regime in Australia and Singapore, it becomes apparent that there are many operational problems that jeopardise the intended object of the legislation, particularly in adjudicating complex payment disputes. The aim of this paper is to explore views of the industry stakeholders regarding some operational problems of statutory adjudication of as well as possible solutions.

Design/methodology/approach

“Expert interviews” method is adopted to collect the empirical data, involving interviews with 23 practitioners from Australia and Singapore.

Findings

The study identified many operational problems jeopardising the attainment of the object of the SOP legislation such as bias of authorised nominating authorities, short adjudication timeframes, inadequate regulations of adjudicators, jurisdictional challenges, involvement of courts and lawyers and complex drafting of the legislation. The study also analysed the views of industry experts with regard to the opportunities for improvement in the operation of the SOP legislation such as following the Queensland model as amended, and introducing a legislative review mechanism and establishing a peer review process. It also suggested specific amendments to make the legislation a more user-friendly.

Practical implications

The implication of this study is a better understanding of the most critical problems inherent in statutory adjudication that need serious consideration by the legislatures and policymakers. In addition, the study also provides some practical measures as suggested by the industry practitioners for each identified problem which may stand as a reliable reference for potential reform in the SOP laws.

Originality/value

There is inadequate empirical research conducted to investigate problems in the operation of statutory adjudication. The study provides original empirical findings which become much necessary nowadays in light of the dynamic moves towards law reform in SOP laws, particularly in Australia. The study provides some practical measures as suggested by the industry practitioners for each identified problem which may stand as a reliable reference for potential reform in the SOP laws.
Property rights revisited – are narratives the way forward?
Authors: Grecksch Kevin , Holzhausen Jessica
Published: June 2017

Purpose

This paper aims to show how property rights predominantly shape discussions about the governance of natural resources and thereby neglect questions of (collective) identities and alternative solutions to govern natural resources. The purpose is to introduce narratives as an alternative approach to the discussion about the governance of natural resources.

Design/methodology/approach

Guided by the question of how we acquire property and what that tells us about our understanding of to whom natural resources belong to, the paper reviews the history of property rights by looking into property theories starting from Thomas Hobbes, John Locke, Adam Smith, Immanuel Kant and Pierre-Joseph Proudhon. It then takes a closer look at The Economics of Ecosystems and Biodiversity (TEEB) study and the Nagoya Protocol with regard to property rights. Second, the paper introduces the concept of narratives surrounding property rights in the past and present.

Findings

Property rights are a social concept dominant in the industrialised world. This has strong implications when looking at the way indigenous people look at natural resources. Mostly, property rights are unknown to them or alternative concepts exist. Yet, documents such as the Nagoya Protocol or the TEEB study presuppose an understanding of property rights originating in European property concepts. A narrative approach to property rights introduces new ideas and looks beyond legislation and policies at the stories people tell about property and natural resources, at property stereotypes and identities and what this might entail for future natural resource governance.

Originality/value

The paper fulfils a need to find alternative approaches to govern natural resources against the background of global environmental challenges.